{"id": "PMID:214403", "title": "Carcinogenesis of N-nitrosodiethylamine (DENA) in chickens and domestic cats.", "content": "The environmental carcinogen N-nitrosodiethylamine (diethylnitrosamine, DENA) has been found to be carcinogenic in 18 animal species. In this study we demonstrate that, after intramuscular injection in chickens, it induces hepatocellular carcinomas of the liver and adenocarcinomas of the kidney. Oral administration in domestic cats causes malignant hepatomas and tumors of the esophagus and kidney. Since DENA is carcinogenic in all species in which it has been tested adequately it can be expected to be a human carcinogen, too.", "contents": "Carcinogenesis of N-nitrosodiethylamine (DENA) in chickens and domestic cats. The environmental carcinogen N-nitrosodiethylamine (diethylnitrosamine, DENA) has been found to be carcinogenic in 18 animal species. In this study we demonstrate that, after intramuscular injection in chickens, it induces hepatocellular carcinomas of the liver and adenocarcinomas of the kidney. Oral administration in domestic cats causes malignant hepatomas and tumors of the esophagus and kidney. Since DENA is carcinogenic in all species in which it has been tested adequately it can be expected to be a human carcinogen, too."}
{"id": "PMID:214404", "title": "Circulating immune complexes in rats bearing chemically induced tumours. II. Characterization of sera from different stages of tumour growth.", "content": "Sera from rats bearing intraperitoneal implants of an aminoazo dye-induced hepatoma were fractionated by Sephadex G200 and DEAE-cellulose ion exchange column chromatography. Isolated fractions were examined for their capacity to bind [125I]C1q as a measure of immune complex levels, and for their ability to bind soluble tumour-specific antigen as well as to react with antigens expressed at the surface of viable hepatoma cells. Elevated levels of circulating immune complexes in unfractionated serum were directly detectable during early tumour development although, following serum fractionation, immune complexes were identified at both early and late stages of tumour growth. The present findings suggest that the detection of immune complexes in unfractionated samples of late tumour-bearer serum using a C1q-binding assay is masked by the increasing production of tumour-specific antibodies and by a shift from complement fixing to non-complement-fixing tumour-specific antibodies.", "contents": "Circulating immune complexes in rats bearing chemically induced tumours. II. Characterization of sera from different stages of tumour growth. Sera from rats bearing intraperitoneal implants of an aminoazo dye-induced hepatoma were fractionated by Sephadex G200 and DEAE-cellulose ion exchange column chromatography. Isolated fractions were examined for their capacity to bind [125I]C1q as a measure of immune complex levels, and for their ability to bind soluble tumour-specific antigen as well as to react with antigens expressed at the surface of viable hepatoma cells. Elevated levels of circulating immune complexes in unfractionated serum were directly detectable during early tumour development although, following serum fractionation, immune complexes were identified at both early and late stages of tumour growth. The present findings suggest that the detection of immune complexes in unfractionated samples of late tumour-bearer serum using a C1q-binding assay is masked by the increasing production of tumour-specific antibodies and by a shift from complement fixing to non-complement-fixing tumour-specific antibodies."}
{"id": "PMID:214405", "title": "Long-term T-cell-mediated immunity to Epstein-Barr virus in man. I. Complete regression of virus-induced transformation in cultures of seropositive donor leukocytes.", "content": "Peripheral blood mononuclear cells from donors of known serological status with respect to EB virus were exposed to the virus in vitro and then cultured at various cell concentrations. All cultures from nine seronegative adult and 12 foetal donors gave rise to cell lines following subculture 4 weeks post infection. In contrast, seropositive donor cultures seeded at the higher cell concentrations developed foci of proliferating EBNA-positive cells within the first 1--2 weeks but thereafter regressed completely and subcultures made after 4 weeks never gave rise to cell lines. Out of 18 seropositive donors tested, 15 showed regression in all cultures seeded at 10(6) cells/ml and above, and with the other three donors a proportion of replicate cultures regressed. T-cell depletion and reconstitution experiments showed that the effect was absolutely dependent upon the presence in the cultures of T cells from these seropositive donors. The results strongly suggest that the regression phenomenon is an in vitro expression of long-term T-cell-mediated immunity to EB virus which the large majority, if not all, infected individuals possess.", "contents": "Long-term T-cell-mediated immunity to Epstein-Barr virus in man. I. Complete regression of virus-induced transformation in cultures of seropositive donor leukocytes. Peripheral blood mononuclear cells from donors of known serological status with respect to EB virus were exposed to the virus in vitro and then cultured at various cell concentrations. All cultures from nine seronegative adult and 12 foetal donors gave rise to cell lines following subculture 4 weeks post infection. In contrast, seropositive donor cultures seeded at the higher cell concentrations developed foci of proliferating EBNA-positive cells within the first 1--2 weeks but thereafter regressed completely and subcultures made after 4 weeks never gave rise to cell lines. Out of 18 seropositive donors tested, 15 showed regression in all cultures seeded at 10(6) cells/ml and above, and with the other three donors a proportion of replicate cultures regressed. T-cell depletion and reconstitution experiments showed that the effect was absolutely dependent upon the presence in the cultures of T cells from these seropositive donors. The results strongly suggest that the regression phenomenon is an in vitro expression of long-term T-cell-mediated immunity to EB virus which the large majority, if not all, infected individuals possess."}
{"id": "PMID:214406", "title": "Malignant lymphoma in four of five siblings.", "content": "In one family four out of five siblings were affected with malignant lymphoma and HD has been diagnosed in two other relatives. HLA-haplotypes were identical for the three diseased siblings who were so studied, whereas for the unaffected one they were different.", "contents": "Malignant lymphoma in four of five siblings. In one family four out of five siblings were affected with malignant lymphoma and HD has been diagnosed in two other relatives. HLA-haplotypes were identical for the three diseased siblings who were so studied, whereas for the unaffected one they were different."}
{"id": "PMID:214407", "title": "Antibodies to Herpes simplex virus types 1 and 2 in patients with squamous-cell carcinoma of uterine cervix in India.", "content": "Antibody activity to Herpes simplex virus type-1 (HSV-1) and type-2 (HSV-2) was measured by the indirect hemagglutination (IHA) test in sera from 124 women with squamous-cell carcinoma of the uterine cervix, 46 women with non-cervical cancer and 116 matched normal women. The type-specific antibodies were assayed by IHA inhibition test. The proportion of cervical cancer cases positive for HSV-2 infection was significantly greater than that of non-cervical cancer cases and matched control women. No difference was observed in the percentages positive for HSV-1 infection among the three study groups. The mean titers of antibodies to HSV-1 as well as HSV-2 were significantly higher than the respective titers in the other two study groups. However, determination of type-specific antibodies did not help in establishing evidence for past infection by HSV-2 in patients with cervical cancer, as no type-specific HSV-2 antibodies were produced in 58% of the cases. The cervical cancer cases were also analysed according to clinical staging (Stages 0 to IV) and histological differentiation of squamous-cell carcinoma. Neither the percentage of positives for HSV-2 infection nor HSV-antibody titers varied, either in clinical staging or in histological differentiation of cervical cancer. These findings suggest that HSV-2 may be related to cervical cancer as an etiological agent but not as a passenger virus of carcinomatous tissue.", "contents": "Antibodies to Herpes simplex virus types 1 and 2 in patients with squamous-cell carcinoma of uterine cervix in India. Antibody activity to Herpes simplex virus type-1 (HSV-1) and type-2 (HSV-2) was measured by the indirect hemagglutination (IHA) test in sera from 124 women with squamous-cell carcinoma of the uterine cervix, 46 women with non-cervical cancer and 116 matched normal women. The type-specific antibodies were assayed by IHA inhibition test. The proportion of cervical cancer cases positive for HSV-2 infection was significantly greater than that of non-cervical cancer cases and matched control women. No difference was observed in the percentages positive for HSV-1 infection among the three study groups. The mean titers of antibodies to HSV-1 as well as HSV-2 were significantly higher than the respective titers in the other two study groups. However, determination of type-specific antibodies did not help in establishing evidence for past infection by HSV-2 in patients with cervical cancer, as no type-specific HSV-2 antibodies were produced in 58% of the cases. The cervical cancer cases were also analysed according to clinical staging (Stages 0 to IV) and histological differentiation of squamous-cell carcinoma. Neither the percentage of positives for HSV-2 infection nor HSV-antibody titers varied, either in clinical staging or in histological differentiation of cervical cancer. These findings suggest that HSV-2 may be related to cervical cancer as an etiological agent but not as a passenger virus of carcinomatous tissue."}
{"id": "PMID:214409", "title": "An e.s.r. and spin-trapping study of the reactions of the SO4- radical with protein and nucleic acid constituents.", "content": "Reactions of the SO4- radical, generated by U.V. photolysis of Na2S2O8, were studied in aqueous solutions of amino acids, dipeptides, nucleic acid bases, nucleosides and nucleotides. The transient free radicals so formed were spin-trapped by t-nitrosobutane and identified by e.s.r. spectroscopy. The amino acids primarily undergo oxidative decarboxylation. The pKs of the ammonium groups of the spin-trapped decarboxylated radicals of glycine and alanine in D2O were determined to be 8.3 +/- 0.2. An oxidation product, which is the precursor of the decarboxylated radical, is tentatively identified for alanine, valine and isoleucine. Radicals formed by hydrogen abstraction by SO-4 are identified for leucine, serine, phenylalanine and 4-hydroxyproline. In dipeptides, SO-4 produces decarboxylation of the amino acid located at the carboxylate terminal residue. For gly-ala and ala-ala, radicals generated by hydrogen abstraction from the carboxylate terminal residue alanine were also characterized. Radicals centered on the C(5) carbon were observed for uracil, cytosine and thymine. For nucleosides and nucleotides, radicals situated on the base and/or the sugar moiety were assigned.", "contents": "An e.s.r. and spin-trapping study of the reactions of the SO4- radical with protein and nucleic acid constituents. Reactions of the SO4- radical, generated by U.V. photolysis of Na2S2O8, were studied in aqueous solutions of amino acids, dipeptides, nucleic acid bases, nucleosides and nucleotides. The transient free radicals so formed were spin-trapped by t-nitrosobutane and identified by e.s.r. spectroscopy. The amino acids primarily undergo oxidative decarboxylation. The pKs of the ammonium groups of the spin-trapped decarboxylated radicals of glycine and alanine in D2O were determined to be 8.3 +/- 0.2. An oxidation product, which is the precursor of the decarboxylated radical, is tentatively identified for alanine, valine and isoleucine. Radicals formed by hydrogen abstraction by SO-4 are identified for leucine, serine, phenylalanine and 4-hydroxyproline. In dipeptides, SO-4 produces decarboxylation of the amino acid located at the carboxylate terminal residue. For gly-ala and ala-ala, radicals generated by hydrogen abstraction from the carboxylate terminal residue alanine were also characterized. Radicals centered on the C(5) carbon were observed for uracil, cytosine and thymine. For nucleosides and nucleotides, radicals situated on the base and/or the sugar moiety were assigned."}
{"id": "PMID:214410", "title": "On the e.s.r. determination of radical yields in X-irradiated amino acids.", "content": "Studies of the temperature dependence of the areas under the e.s.r. absorption spectra of X-ray-induced free radicals in amino acids at various power levels and of power saturation at different temperatures are reported. They indicate that power saturation is responsible for the anomalous Curie--Weiss behaviour previously reported. The consequences of power saturation to the e.s.r. determination of radical yields are discussed. The effect of impurity e.s.r. signals in amino acids on quantitative e.s.r. determinations is also discussed.", "contents": "On the e.s.r. determination of radical yields in X-irradiated amino acids. Studies of the temperature dependence of the areas under the e.s.r. absorption spectra of X-ray-induced free radicals in amino acids at various power levels and of power saturation at different temperatures are reported. They indicate that power saturation is responsible for the anomalous Curie--Weiss behaviour previously reported. The consequences of power saturation to the e.s.r. determination of radical yields are discussed. The effect of impurity e.s.r. signals in amino acids on quantitative e.s.r. determinations is also discussed."}
{"id": "PMID:214413", "title": "[Classification of vascular neoplasms].", "content": "Neoplasms of blood and lymph vessels differ from angiectatic and angiokeratotic nevi by real proliferating growth. According to their features of growth and their wall structures, they are classified into three main groups: angiomas, glomangiomas and malignant vascular tumors. Within the angiomas on the one hand, capillary angiomas are classified into: planotuberous and tuberonodous angiomas of childhood and Kasabach-Merritt syndrome, multilocular hemangiomatosis, progressive multiple angiomas, tardive (\"senile\") angiomas, eruptive angiomas (granulomata pediculata), papular angioplasia, gemmangioma, and benign juvenile hemangioendothelioma. On the other hand, cavernous angiomas, i.e. arterial and venous cavernomas, as well as blue rubberbleb nevus, Mafucci's syndrome, angioleiomyoma, benign juvenile hemangiopericytoma and cavernous lymphangioma, form thick walled structures without involution. Glomangiomas occur as solitary, multiple systematized, and multiple disseminated and familiar forms. Within the group of malignant vascular tumors--Kaposi sarcoma, lymphangiosarcoma in lymphedema, hemangioendothelioma and angioplastic reticulosarcoma, hemangio- or lymphangiosarcoma, angioendotheliomastosis proliferans, rarity and increasing loss of characteristic differentiated structures give rise to difficulties in nosologic classification.", "contents": "[Classification of vascular neoplasms]. Neoplasms of blood and lymph vessels differ from angiectatic and angiokeratotic nevi by real proliferating growth. According to their features of growth and their wall structures, they are classified into three main groups: angiomas, glomangiomas and malignant vascular tumors. Within the angiomas on the one hand, capillary angiomas are classified into: planotuberous and tuberonodous angiomas of childhood and Kasabach-Merritt syndrome, multilocular hemangiomatosis, progressive multiple angiomas, tardive (\"senile\") angiomas, eruptive angiomas (granulomata pediculata), papular angioplasia, gemmangioma, and benign juvenile hemangioendothelioma. On the other hand, cavernous angiomas, i.e. arterial and venous cavernomas, as well as blue rubberbleb nevus, Mafucci's syndrome, angioleiomyoma, benign juvenile hemangiopericytoma and cavernous lymphangioma, form thick walled structures without involution. Glomangiomas occur as solitary, multiple systematized, and multiple disseminated and familiar forms. Within the group of malignant vascular tumors--Kaposi sarcoma, lymphangiosarcoma in lymphedema, hemangioendothelioma and angioplastic reticulosarcoma, hemangio- or lymphangiosarcoma, angioendotheliomastosis proliferans, rarity and increasing loss of characteristic differentiated structures give rise to difficulties in nosologic classification."}
{"id": "PMID:214414", "title": "[Multinodular reticulohistiocytosis in the adult. Clinical picture, histology and electron microscopy].", "content": "Multiple nodular infiltrates of reticulohistiocytic cells may progressively develop in human adult skin showing intracellular lipid storage (neutral lipids, phospholipids, free cholesterin), without changes of the lipid levels in blood. These are obviously benign reactive lesions, which may spontaneously disappear. Concomitant skin or systemic diseases may occur. According to the individual data of each case several names are given to the skin lesions which seem to represent variants of the same entity. The cell infiltrate may predominantly consist of histiocytes, giant cells or lipid storing (foam) cells. Ultrastructural examination did not reveal specific types of lipids or specific types of intracellular storage; however, it seems necessary, in order to differentiate this entity from histiocytosis X: dermal Langerhans cells are lacking in this disease.", "contents": "[Multinodular reticulohistiocytosis in the adult. Clinical picture, histology and electron microscopy]. Multiple nodular infiltrates of reticulohistiocytic cells may progressively develop in human adult skin showing intracellular lipid storage (neutral lipids, phospholipids, free cholesterin), without changes of the lipid levels in blood. These are obviously benign reactive lesions, which may spontaneously disappear. Concomitant skin or systemic diseases may occur. According to the individual data of each case several names are given to the skin lesions which seem to represent variants of the same entity. The cell infiltrate may predominantly consist of histiocytes, giant cells or lipid storing (foam) cells. Ultrastructural examination did not reveal specific types of lipids or specific types of intracellular storage; however, it seems necessary, in order to differentiate this entity from histiocytosis X: dermal Langerhans cells are lacking in this disease."}
{"id": "PMID:214417", "title": "Histoenzymological analysis of mesencephalic auditory, tegmental and cranial nerve nuclei in the frog (Rana tigrina).", "content": "The distributions of acid and alkaline phosphatases, 5-nucleotidase, ATPase, non-specific esterase, specific cholinesterase, succinic dehydrogenase and beta-galactosidase are described in the mesencephalic auditory, tegmental and cranial nerve nuclei of the frog (Rana tigrina). The main results of the study are as follows: The laminar, principal, and magnocellular nuclei of the torus semicircularis, which are associated with auditory functions, show intense activity of specific cholinesterase. On the other hand, the commissural and subependymal mid-line nuclei, whose functions are doubtful, show a complete lack of this enzyme. The nucleus isthmi shows intense acid phosphatase, ATPase, non-specific esterase, specific cholinesterase and succinic dehydrogenase activities. Non-specific esterase is virtually absent from all the areas studied except the nucleus isthmi and the 3rd and 4th cranial nerve nuclei. Most of the commissures and fibre tracts show intense activity for beta-galactosidase and 5-nucleotidase. The possible roles of these enzymes in glycolipid and myelin metabolism are discussed.", "contents": "Histoenzymological analysis of mesencephalic auditory, tegmental and cranial nerve nuclei in the frog (Rana tigrina). The distributions of acid and alkaline phosphatases, 5-nucleotidase, ATPase, non-specific esterase, specific cholinesterase, succinic dehydrogenase and beta-galactosidase are described in the mesencephalic auditory, tegmental and cranial nerve nuclei of the frog (Rana tigrina). The main results of the study are as follows: The laminar, principal, and magnocellular nuclei of the torus semicircularis, which are associated with auditory functions, show intense activity of specific cholinesterase. On the other hand, the commissural and subependymal mid-line nuclei, whose functions are doubtful, show a complete lack of this enzyme. The nucleus isthmi shows intense acid phosphatase, ATPase, non-specific esterase, specific cholinesterase and succinic dehydrogenase activities. Non-specific esterase is virtually absent from all the areas studied except the nucleus isthmi and the 3rd and 4th cranial nerve nuclei. Most of the commissures and fibre tracts show intense activity for beta-galactosidase and 5-nucleotidase. The possible roles of these enzymes in glycolipid and myelin metabolism are discussed."}
{"id": "PMID:214418", "title": "Isolation and characterization of a membrane-bound, low-potential c-type cytochrome from purple photosynthetic bacteria, with special reference to Rhodospirillum rubrum.", "content": "Other investigators have isolated soluble, low-potential, c-type cytochromes (cytochrome c3) from a few photosynthetic procaryotes, i.e., a cyanobacterium and two species of purple nonsulfur bacteria. However, such cytochromes appeared to be absent from other purple bacteria, including Rhodospirillum rubrum and Chromatium vinosum. We now report evidence for the presence of low-potential c-type cytochromes in these two species, in which they were found to be bound to the photosynthetic membranes. Evidence for a membrane-bound, low-potential c-type cytochrome was also found in Rhodopseudomonas sphaeoides. The low-potential c-type cytochrome of R. rubrum was solubilized by a Triton X-100 treatment of chromatophores and was partly purified. It was found to have a molecular weight of about 17,000, a midpoint oxidation-reduction potential of -192 mV, and an alpha-absorption peak at 552 nm. It appears that low-potential c-type cytochromes may be present in all purple photosynthetic bacteria, of both the sulfur and the nonsulfur types.", "contents": "Isolation and characterization of a membrane-bound, low-potential c-type cytochrome from purple photosynthetic bacteria, with special reference to Rhodospirillum rubrum. Other investigators have isolated soluble, low-potential, c-type cytochromes (cytochrome c3) from a few photosynthetic procaryotes, i.e., a cyanobacterium and two species of purple nonsulfur bacteria. However, such cytochromes appeared to be absent from other purple bacteria, including Rhodospirillum rubrum and Chromatium vinosum. We now report evidence for the presence of low-potential c-type cytochromes in these two species, in which they were found to be bound to the photosynthetic membranes. Evidence for a membrane-bound, low-potential c-type cytochrome was also found in Rhodopseudomonas sphaeoides. The low-potential c-type cytochrome of R. rubrum was solubilized by a Triton X-100 treatment of chromatophores and was partly purified. It was found to have a molecular weight of about 17,000, a midpoint oxidation-reduction potential of -192 mV, and an alpha-absorption peak at 552 nm. It appears that low-potential c-type cytochromes may be present in all purple photosynthetic bacteria, of both the sulfur and the nonsulfur types."}
{"id": "PMID:214419", "title": "Isolation and characterization of extragenic suppressor strains of Corynebacterium diphtheriae.", "content": "The isolation and characterization of two different nonsense suppressor strains of Corynebacterium diphtheriae C7 sup+(-)tox- are described. Appropriate lysogens of these strains with corynephage beta, carrying known class II tox premature polypeptide chain termination mutations [C7sup-1(betatox-30) and C7sup-2(betatox-45)], each produce a 62,000-dalton polypeptide with nicotinamide adenine dinucleotide: elongation factor-2 adenosine diphosphate ribosyltransferase activity in addition to a chain-terminated polypeptide of 30,000 or 45,000 daltons, respectively. In addition, purified protein of 62,000 daltons, resulting from the suppression of the nonsense mutations tox-30 and tox-45, will react with antisera purified against the terminal 17,000 daltons of the toxin molecule and are immunologically identical to toxin by radial immunodiffusion. The suppression pattern of lysogenic derivatives of C7sup-1(-)tox- and C7sup-2(-)tox- with other class II and III mutants of corynephage beta was determined.", "contents": "Isolation and characterization of extragenic suppressor strains of Corynebacterium diphtheriae. The isolation and characterization of two different nonsense suppressor strains of Corynebacterium diphtheriae C7 sup+(-)tox- are described. Appropriate lysogens of these strains with corynephage beta, carrying known class II tox premature polypeptide chain termination mutations [C7sup-1(betatox-30) and C7sup-2(betatox-45)], each produce a 62,000-dalton polypeptide with nicotinamide adenine dinucleotide: elongation factor-2 adenosine diphosphate ribosyltransferase activity in addition to a chain-terminated polypeptide of 30,000 or 45,000 daltons, respectively. In addition, purified protein of 62,000 daltons, resulting from the suppression of the nonsense mutations tox-30 and tox-45, will react with antisera purified against the terminal 17,000 daltons of the toxin molecule and are immunologically identical to toxin by radial immunodiffusion. The suppression pattern of lysogenic derivatives of C7sup-1(-)tox- and C7sup-2(-)tox- with other class II and III mutants of corynephage beta was determined."}
{"id": "PMID:214420", "title": "Catabolite-repression-like phenomenon in Rhizobium meliloti.", "content": "We report a phenomenon similar to catabolite repression in Rhizobium meliloti. Succinate, which allows the highest observed rate of growth of R. meliloti, caused an immediate reduction of beta-galactosidase activity when added to cells growing in lactose. A Lac- mutant was unaltered in nodulation and nitrogen fixation capacities, but a pleiotropic mutant deficient in several catabolic properties was unable to produce effective nitrogen-fixing nodules.", "contents": "Catabolite-repression-like phenomenon in Rhizobium meliloti. We report a phenomenon similar to catabolite repression in Rhizobium meliloti. Succinate, which allows the highest observed rate of growth of R. meliloti, caused an immediate reduction of beta-galactosidase activity when added to cells growing in lactose. A Lac- mutant was unaltered in nodulation and nitrogen fixation capacities, but a pleiotropic mutant deficient in several catabolic properties was unable to produce effective nitrogen-fixing nodules."}
{"id": "PMID:214421", "title": "Effects of altered rho gene product on the expression of the Escherichia coli histidine operon.", "content": "An altered rho gene product affects expression of the his operon of Escherichia coli. The effect is greater for the operator proximal portion of the his operon than for the operator distal portion. This \"rho effect\" appears to be independent of the site of action of hisT-altered histidyl-tRNA.", "contents": "Effects of altered rho gene product on the expression of the Escherichia coli histidine operon. An altered rho gene product affects expression of the his operon of Escherichia coli. The effect is greater for the operator proximal portion of the his operon than for the operator distal portion. This \"rho effect\" appears to be independent of the site of action of hisT-altered histidyl-tRNA."}
{"id": "PMID:214422", "title": "Cell fractions and enzymatic activities of Ureaplasma urealyticum.", "content": "The localization of some enzymic activities in cell fractions of Ureaplasma urealyticum was studied. A quantitative evaluation of the effectiveness of several cell lysis procedures was obtained by using labeled membranes and sucrose density gradient centrifugation. Ultrasonic treatment was found to be the most effective procedure for lysing the cells, whereas digitonin and osmotic shock caused the lysis of only 70 and 50% of the cells, respectively. The localization of selected enzymes in Ureaplasma cells resembled that found in other Mycoplasma species. Adenosine triphosphatase, ribonuclease, deoxyribonuclease, and p-nitrophenylphosphatase activities were located exclusively in the membrane fraction, whereas urease and L-histidine ammonia-lyase were located in the cytoplasm.", "contents": "Cell fractions and enzymatic activities of Ureaplasma urealyticum. The localization of some enzymic activities in cell fractions of Ureaplasma urealyticum was studied. A quantitative evaluation of the effectiveness of several cell lysis procedures was obtained by using labeled membranes and sucrose density gradient centrifugation. Ultrasonic treatment was found to be the most effective procedure for lysing the cells, whereas digitonin and osmotic shock caused the lysis of only 70 and 50% of the cells, respectively. The localization of selected enzymes in Ureaplasma cells resembled that found in other Mycoplasma species. Adenosine triphosphatase, ribonuclease, deoxyribonuclease, and p-nitrophenylphosphatase activities were located exclusively in the membrane fraction, whereas urease and L-histidine ammonia-lyase were located in the cytoplasm."}
{"id": "PMID:214423", "title": "Co-induction of beta-galactosidase and the lactose-P-enolpyruvate phosphotransferase system in Streptococcus salivarius and Streptococcus mutans.", "content": "The addition of lactose, galactose, or isopropyl-beta-D-thiogalactoside (IPTG) to glucose-grown cells of Streptococcus salivarius 25975 resulted in the co-induction of both the lactose-P-enolpyruvate phosphotransferase system (lactose-PTS) and beta-galactosidase, with the latter the predominant metabolic system. With various strains of Streptococcus mutans and Streptococcus sanguis 10556, on the other hand, the lactose-PTS was the major metabolic pathway with beta-galactosidase induced either to low or negligible levels. In all cases, induction of the lactose-PTS resulted in the concomitant induction of 6-P-beta-galactosidase. The induction by lactose of both the lactose-PTS and beta-galactosidase in all strains was repressed by glucose and other catabolites, notably, fructose. Induction of beta-galactosidase in S. salivarius 25975 by IPTG was, however, relatively resistant to glucose repression. Induction experiments with IPTG and lactose suggested that a cellular metabolite of lactose metabolism was a repressor of enzyme activity. Exogenous cAMP was shown to reverse the transient repression by glucose of beta-galactosidase induction in cells of S. salivarius 25975 receiving lactose, provided the cells were grown with small amounts of toluene to overcome the permeability barrier to this nucleotide, cAMP, was however, unable to overcome the permanent repression of beta-galactosidase activity to a significant extent under these conditions.", "contents": "Co-induction of beta-galactosidase and the lactose-P-enolpyruvate phosphotransferase system in Streptococcus salivarius and Streptococcus mutans. The addition of lactose, galactose, or isopropyl-beta-D-thiogalactoside (IPTG) to glucose-grown cells of Streptococcus salivarius 25975 resulted in the co-induction of both the lactose-P-enolpyruvate phosphotransferase system (lactose-PTS) and beta-galactosidase, with the latter the predominant metabolic system. With various strains of Streptococcus mutans and Streptococcus sanguis 10556, on the other hand, the lactose-PTS was the major metabolic pathway with beta-galactosidase induced either to low or negligible levels. In all cases, induction of the lactose-PTS resulted in the concomitant induction of 6-P-beta-galactosidase. The induction by lactose of both the lactose-PTS and beta-galactosidase in all strains was repressed by glucose and other catabolites, notably, fructose. Induction of beta-galactosidase in S. salivarius 25975 by IPTG was, however, relatively resistant to glucose repression. Induction experiments with IPTG and lactose suggested that a cellular metabolite of lactose metabolism was a repressor of enzyme activity. Exogenous cAMP was shown to reverse the transient repression by glucose of beta-galactosidase induction in cells of S. salivarius 25975 receiving lactose, provided the cells were grown with small amounts of toluene to overcome the permeability barrier to this nucleotide, cAMP, was however, unable to overcome the permanent repression of beta-galactosidase activity to a significant extent under these conditions."}
{"id": "PMID:214424", "title": "Regulation of lac operon expression: reappraisal of the theory of catabolite repression.", "content": "The physiological state of Escherichia coli with respect to (permanent) catabolite repression was assessed by measuring the steady-state level of beta-galactosidase in induced or in constitutive cells under a variety of growth conditions. Four results were obtained. (i) Catabolite repression had a major effect on fully induced or constitutive expression of the lac gene, and the magnitude of this effect was found to be dependent on the promoter structure; cells with a wild-type lac promoter showed an 18-fold variation in lac expression, and cells with the lacP37 (formerly lac-L37) promoter exhibited several hundred-fold variation. (ii) Exogenous adenosine cyclic 3',5'-monophosphoric acid (cAMP) could not abolish catabolite repression, even though several controls demonstrated that cAMP was entering the cells in significant amounts. (Rapid intracellular degradation of cAMP could not be ruled out.) (iii) Neither the growth rate nor the presence of biosynthetic products altered the degree of catabolite repression; all variation could be related to the catabolites present in the growth medium. (iv) Slowing by imposing an amino acid restriction decreased the differential rate of beta-galactosidase synthesis from the wild-type lac promoter when bacteria were cultured in either the absence or presence of cAMP; this decreased lac expression also occurred when the bacteria harbored the catabolite-insensitive lacP5 (formerly lacUV5) promoter mutation. These findings support the idea that (permanent) catabolite repression is set by the catabolites in the growth medium and may not be related to an imbalance between catabolism and anabolism.", "contents": "Regulation of lac operon expression: reappraisal of the theory of catabolite repression. The physiological state of Escherichia coli with respect to (permanent) catabolite repression was assessed by measuring the steady-state level of beta-galactosidase in induced or in constitutive cells under a variety of growth conditions. Four results were obtained. (i) Catabolite repression had a major effect on fully induced or constitutive expression of the lac gene, and the magnitude of this effect was found to be dependent on the promoter structure; cells with a wild-type lac promoter showed an 18-fold variation in lac expression, and cells with the lacP37 (formerly lac-L37) promoter exhibited several hundred-fold variation. (ii) Exogenous adenosine cyclic 3',5'-monophosphoric acid (cAMP) could not abolish catabolite repression, even though several controls demonstrated that cAMP was entering the cells in significant amounts. (Rapid intracellular degradation of cAMP could not be ruled out.) (iii) Neither the growth rate nor the presence of biosynthetic products altered the degree of catabolite repression; all variation could be related to the catabolites present in the growth medium. (iv) Slowing by imposing an amino acid restriction decreased the differential rate of beta-galactosidase synthesis from the wild-type lac promoter when bacteria were cultured in either the absence or presence of cAMP; this decreased lac expression also occurred when the bacteria harbored the catabolite-insensitive lacP5 (formerly lacUV5) promoter mutation. These findings support the idea that (permanent) catabolite repression is set by the catabolites in the growth medium and may not be related to an imbalance between catabolism and anabolism."}
{"id": "PMID:214425", "title": "Stoichiometric studies on the oxidation of tetrahydropterin with ferri-cytochrome c.", "content": "The oxidation of tetrahydropterin with ferri-cytochrome c was studied using a tetrahydropterin-generating system composed of dihydropteridine reductase [EC 1.6.99.7] and NADH. Under aerobic conditions, 1.5 to 1.8 mol of cytochrome c was reduced per mol of NADH, whereas 2 mol of cytochrome c was reduced under anaerobic conditions. When superoxide dismutase [EC 1.15.1.1] was added to the system under aerobic conditions, only 1 mol of cytochrome c was reduced per mol of NADH, while the pterin oxidation was scarcely affected. Based on these results, we propose that the oxidation of tetrahydropterin to quinonoid dihydropterin proceeds via two steps: tetrahydropterin is first oxidized by ferri-cytochrome c to give a pterin intermediate, which has lost one electron, then in turn this reduces O2 to form O2-.", "contents": "Stoichiometric studies on the oxidation of tetrahydropterin with ferri-cytochrome c. The oxidation of tetrahydropterin with ferri-cytochrome c was studied using a tetrahydropterin-generating system composed of dihydropteridine reductase [EC 1.6.99.7] and NADH. Under aerobic conditions, 1.5 to 1.8 mol of cytochrome c was reduced per mol of NADH, whereas 2 mol of cytochrome c was reduced under anaerobic conditions. When superoxide dismutase [EC 1.15.1.1] was added to the system under aerobic conditions, only 1 mol of cytochrome c was reduced per mol of NADH, while the pterin oxidation was scarcely affected. Based on these results, we propose that the oxidation of tetrahydropterin to quinonoid dihydropterin proceeds via two steps: tetrahydropterin is first oxidized by ferri-cytochrome c to give a pterin intermediate, which has lost one electron, then in turn this reduces O2 to form O2-."}
{"id": "PMID:214426", "title": "Diffusion-potential-induced oxidation and reduction of cytochromes in chromatophores from Rhodopseudomonas sphaeroides.", "content": "A membrane potential jump was induced by the addition of valinomycin in the presence of a KCl concentration gradient across the membrane of Rhodopseudomonas sphaeroides chromatophores. As well as a carotenoid band shift, which is known to be an indicator of membrane potential, absorbance changes due to the oxidation-reduction reactions of cytochromes accompanied the jump. Under aerobic conditions with no reductant added, a part of cytochrome c2 was reduced by an inside-positive potential jump of about 100 mV in the time range of tens of seconds. This can be explained by the location of the cytochrome on the inner side of the chromatophore membrane and electrophoretic flow of electrons across the membrane. On the other hand, in the presence of 1 mM ascorbate, a similar jump of membrane potential induced a rapid oxidation of cytochrome c2 and a subsequent reduction. A rapid reduction of b-type cytochrome was also observed. Antimycin A inhibited the c2 oxidation, but did not inhibit the b reduction. The oxidation of cytochrome c2 may be explained by a diffusion-potential-induced electron flow to cytochrome b and a simultaneous electron donation by cytochrome b and cytochrome c2 to a common electron acceptor, possibly a quinone.", "contents": "Diffusion-potential-induced oxidation and reduction of cytochromes in chromatophores from Rhodopseudomonas sphaeroides. A membrane potential jump was induced by the addition of valinomycin in the presence of a KCl concentration gradient across the membrane of Rhodopseudomonas sphaeroides chromatophores. As well as a carotenoid band shift, which is known to be an indicator of membrane potential, absorbance changes due to the oxidation-reduction reactions of cytochromes accompanied the jump. Under aerobic conditions with no reductant added, a part of cytochrome c2 was reduced by an inside-positive potential jump of about 100 mV in the time range of tens of seconds. This can be explained by the location of the cytochrome on the inner side of the chromatophore membrane and electrophoretic flow of electrons across the membrane. On the other hand, in the presence of 1 mM ascorbate, a similar jump of membrane potential induced a rapid oxidation of cytochrome c2 and a subsequent reduction. A rapid reduction of b-type cytochrome was also observed. Antimycin A inhibited the c2 oxidation, but did not inhibit the b reduction. The oxidation of cytochrome c2 may be explained by a diffusion-potential-induced electron flow to cytochrome b and a simultaneous electron donation by cytochrome b and cytochrome c2 to a common electron acceptor, possibly a quinone."}
{"id": "PMID:214427", "title": "A signal sequence for the insertion of a transmembrane glycoprotein. Similarities to the signals of secretory proteins in primary structure and function.", "content": "The biosynthesis of a secretory protein and a transmembrane viral glycoprotein are compared by two different experimental approaches. (a) NH2-terminal sequence analysis has been performed on various forms of the transmembrane glycoprotein of vesicular stomatitis virus synthesized in cell-free systems. The sequence data presented demonstrate that the nascent precursor of the glycoprotein contains a \"signal sequence\" of 16 amino acids at the NH2 terminus, whose sequence is Met-Lys-Cys-Leu-Leu-Tyr-Leu-Ala-Phe-Leu-Phe-Ile-(His-Val-Asn)-Cys. This signal sequence is proteolytically cleaved during the process of insertion into microsomal membranes prior to chain completion. The new NH2 terminus of the inserted, cleaved, and glycosylated membrane protein is located within the lumen of the microsomal vesicles and is identical to that of the authentic glycoprotein from virions. (b) Nascent chain competition experiments were performed between this glycoprotein, bovine pituitary prolactin (a secretory protein), and rabbit globin (a cytosolic protein). It was found that the nascent membrane glycoprotein, but not nascent globin, competed with nascent prolactin for membrane sites involved in the early biosynthetic event of transfer across membranes. These data suggest that an initially common pathway is involved in the biogenesis of secretory proteins and at least one class of integral membrane proteins.", "contents": "A signal sequence for the insertion of a transmembrane glycoprotein. Similarities to the signals of secretory proteins in primary structure and function. The biosynthesis of a secretory protein and a transmembrane viral glycoprotein are compared by two different experimental approaches. (a) NH2-terminal sequence analysis has been performed on various forms of the transmembrane glycoprotein of vesicular stomatitis virus synthesized in cell-free systems. The sequence data presented demonstrate that the nascent precursor of the glycoprotein contains a \"signal sequence\" of 16 amino acids at the NH2 terminus, whose sequence is Met-Lys-Cys-Leu-Leu-Tyr-Leu-Ala-Phe-Leu-Phe-Ile-(His-Val-Asn)-Cys. This signal sequence is proteolytically cleaved during the process of insertion into microsomal membranes prior to chain completion. The new NH2 terminus of the inserted, cleaved, and glycosylated membrane protein is located within the lumen of the microsomal vesicles and is identical to that of the authentic glycoprotein from virions. (b) Nascent chain competition experiments were performed between this glycoprotein, bovine pituitary prolactin (a secretory protein), and rabbit globin (a cytosolic protein). It was found that the nascent membrane glycoprotein, but not nascent globin, competed with nascent prolactin for membrane sites involved in the early biosynthetic event of transfer across membranes. These data suggest that an initially common pathway is involved in the biogenesis of secretory proteins and at least one class of integral membrane proteins."}
{"id": "PMID:214428", "title": "Calcium-dependent 3':5'-cyclic nucleotide phosphodiesterase. Inhibition of basal activity at physiological levels of potassium ions.", "content": "A calcium-dependent cyclic nucleotide phosphodiesterase from rat cerebrum was, in the absence of activator protein, inhibited by various monovalent cations. The inhibition was rapid, readily reversible, and concentration-dependent, with 100 mM cesium, rubidium, or potassium ion inhibiting essentially all basal enzyme activity, while 100 mM sodium or lithium ions produced only moderate inhibition. The potency of the cations in inhibiting the enzyme was Cs greater than or equal to Rb greater than K greater than Na greater than or equal to Li. Potassium ions increased the apparent Km for cyclic GMP and cyclic AMP by 3- and 5-fold, respectively. At 100 mM, the monovalent cations inhibited enzyme activated by the calcium-dependent activator by only 15 to 30%, while at 55 mM no inhibition pertained. Potassium and sodium ions at 55 mM had no effect on the calcium-independent phosphodiesterase from rat cerebrum. The results indicate that at normal intracellular concentrations of potassium ions the activity of the calcium-dependent phosphodiesterase is virtually completely dependent on the presence of calcium plus activator protein.", "contents": "Calcium-dependent 3':5'-cyclic nucleotide phosphodiesterase. Inhibition of basal activity at physiological levels of potassium ions. A calcium-dependent cyclic nucleotide phosphodiesterase from rat cerebrum was, in the absence of activator protein, inhibited by various monovalent cations. The inhibition was rapid, readily reversible, and concentration-dependent, with 100 mM cesium, rubidium, or potassium ion inhibiting essentially all basal enzyme activity, while 100 mM sodium or lithium ions produced only moderate inhibition. The potency of the cations in inhibiting the enzyme was Cs greater than or equal to Rb greater than K greater than Na greater than or equal to Li. Potassium ions increased the apparent Km for cyclic GMP and cyclic AMP by 3- and 5-fold, respectively. At 100 mM, the monovalent cations inhibited enzyme activated by the calcium-dependent activator by only 15 to 30%, while at 55 mM no inhibition pertained. Potassium and sodium ions at 55 mM had no effect on the calcium-independent phosphodiesterase from rat cerebrum. The results indicate that at normal intracellular concentrations of potassium ions the activity of the calcium-dependent phosphodiesterase is virtually completely dependent on the presence of calcium plus activator protein."}
{"id": "PMID:214429", "title": "Substrate inhibition of the mitochondrial and cytoplasmic malate dehydrogenases.", "content": "The mechanism that leads to an inhibition of enzyme activity in the presence of high concentrations of substrate was investigated with the two malate dehydrogenase isoenzymes obtained from pig heart. The inhibition is promoted by an abortive binary complex formed by the enzymes and the enol form of of oxalacelate. Neither the oxidized coenzyme nor the reduced coenzyme appears to be involved in the formation of this complex. These results suggest that the mechanism of substrate inhibition that occurs with the pig heart malate dehydrogenases is different from that observed with the lactate dehydrogenases from chicken hearts. The inhibition constants for oxalacetate are 2.0 mM with the mitochondrial enzyme and 4.5 mM with the cytoplasmic enzyme. Since the in vivo concentration of oxalacetate is reported to be about 10 micrometer, these data suggest that the substrate inhibition that is exhibited by the malate dehydrogenases may not be of any significance in vivo.", "contents": "Substrate inhibition of the mitochondrial and cytoplasmic malate dehydrogenases. The mechanism that leads to an inhibition of enzyme activity in the presence of high concentrations of substrate was investigated with the two malate dehydrogenase isoenzymes obtained from pig heart. The inhibition is promoted by an abortive binary complex formed by the enzymes and the enol form of of oxalacelate. Neither the oxidized coenzyme nor the reduced coenzyme appears to be involved in the formation of this complex. These results suggest that the mechanism of substrate inhibition that occurs with the pig heart malate dehydrogenases is different from that observed with the lactate dehydrogenases from chicken hearts. The inhibition constants for oxalacetate are 2.0 mM with the mitochondrial enzyme and 4.5 mM with the cytoplasmic enzyme. Since the in vivo concentration of oxalacetate is reported to be about 10 micrometer, these data suggest that the substrate inhibition that is exhibited by the malate dehydrogenases may not be of any significance in vivo."}
{"id": "PMID:214433", "title": "Characterization of NADH-cytochrome c reductase, a component of benzoate 1,2-dioxygenase system from Pseudomonas arvilla c-1.", "content": "NADH-cytochrome c reductase, a component of benzoate 1,2-dioxygenase system, was purified to homogeneity, as judged by sodium dodecyl sulfate disc gel electrophoresis and ultracentrifugation, from benzoate-induced cells of Pseudomonas arvilla. The molecular weight of the enzyme was determined to be 38,300 by sedimentation equilibrium analysis, 37,000 by Sephadex G-100 gel filtration, and 37,500 by sodium dodecyl sulfate disc gel electrophoresis, respectively, indicating that the enzyme consisted of a single polypeptide chain. The sedimentation coefficient was calculated to be 3.3 S. The Stokes radius for the enzyme was calculated to be 27 A. The isoelectric point of the enzyme was estimated to be pH 4.2. The enzyme contained 1 mol of FAD, 2 mol of iron, and 2 mol of labile sulfide/mol of enzyme. It exhibited absorption spectrum with maxima at 273, 340, 402, and 467 nm. Amino acid analysis of the enzyme revealed that it was devoid of tryptophan. The enzyme contained 9 mol of cysteine/mol of enzyme but no disulfide linkage. The turnover number of the enzyme for the NADH-dependent reduction of cytochrome c was 17,100 at 24 degrees C. Although NADPH also acted as an electron donor, NADH was highly superior to NADPH. Ferricyanide and 2,6-dichlorophenolindophenol served as electron acceptors. Certain other properties of the enzyme are also presented.", "contents": "Characterization of NADH-cytochrome c reductase, a component of benzoate 1,2-dioxygenase system from Pseudomonas arvilla c-1. NADH-cytochrome c reductase, a component of benzoate 1,2-dioxygenase system, was purified to homogeneity, as judged by sodium dodecyl sulfate disc gel electrophoresis and ultracentrifugation, from benzoate-induced cells of Pseudomonas arvilla. The molecular weight of the enzyme was determined to be 38,300 by sedimentation equilibrium analysis, 37,000 by Sephadex G-100 gel filtration, and 37,500 by sodium dodecyl sulfate disc gel electrophoresis, respectively, indicating that the enzyme consisted of a single polypeptide chain. The sedimentation coefficient was calculated to be 3.3 S. The Stokes radius for the enzyme was calculated to be 27 A. The isoelectric point of the enzyme was estimated to be pH 4.2. The enzyme contained 1 mol of FAD, 2 mol of iron, and 2 mol of labile sulfide/mol of enzyme. It exhibited absorption spectrum with maxima at 273, 340, 402, and 467 nm. Amino acid analysis of the enzyme revealed that it was devoid of tryptophan. The enzyme contained 9 mol of cysteine/mol of enzyme but no disulfide linkage. The turnover number of the enzyme for the NADH-dependent reduction of cytochrome c was 17,100 at 24 degrees C. Although NADPH also acted as an electron donor, NADH was highly superior to NADPH. Ferricyanide and 2,6-dichlorophenolindophenol served as electron acceptors. Certain other properties of the enzyme are also presented."}
{"id": "PMID:214435", "title": "Heterogeneity of amino acid sequence in hippopotamus cytochrome c.", "content": "The amino acid sequences of chymotryptic and tryptic peptides of Hippopotamus amphibius cytochrome c were determined by a recent modification of the manual Edman sequential degradation procedure. They were ordered by comparison with the structure of the hog protein. The hippopotamus protein differs in three positions: serine, alanine, and glutamine replace alanine, glutamic acid, and lysine in positions 43, 92, and 100, respectively. Since the artiodactyl suborders diverged in the mid-Eocene some 50 million years ago, the fact that representatives of some of them show no differences in their cytochromes c (cow, sheep, and hog), while another exhibits as many as three such differences, verifies that even in relatively closely related lines of descent the rate at which cytochrome c changes in the course of evolution is not constant. Furthermore, 10.6% of the hippopotamus cytochrome c preparation was shown to contain isoleucine instead of valine at position 3, indicating that one of the four animals from which the protein was obtained was heterozygous in the cytochrome c gene. Such heterogeneity is a necessary condition of evolutionary variation and has not been previously observed in the cytochrome c of a wild mammalian population.", "contents": "Heterogeneity of amino acid sequence in hippopotamus cytochrome c. The amino acid sequences of chymotryptic and tryptic peptides of Hippopotamus amphibius cytochrome c were determined by a recent modification of the manual Edman sequential degradation procedure. They were ordered by comparison with the structure of the hog protein. The hippopotamus protein differs in three positions: serine, alanine, and glutamine replace alanine, glutamic acid, and lysine in positions 43, 92, and 100, respectively. Since the artiodactyl suborders diverged in the mid-Eocene some 50 million years ago, the fact that representatives of some of them show no differences in their cytochromes c (cow, sheep, and hog), while another exhibits as many as three such differences, verifies that even in relatively closely related lines of descent the rate at which cytochrome c changes in the course of evolution is not constant. Furthermore, 10.6% of the hippopotamus cytochrome c preparation was shown to contain isoleucine instead of valine at position 3, indicating that one of the four animals from which the protein was obtained was heterozygous in the cytochrome c gene. Such heterogeneity is a necessary condition of evolutionary variation and has not been previously observed in the cytochrome c of a wild mammalian population."}
{"id": "PMID:214436", "title": "Inhibition of cyclic AMP-dependent protein kinase by analogues of a synthetic peptide substrate.", "content": "Analogues of the synthetic substrate Leu-Arg-Arg-Ala-Ser-Leu-Gly in which the serine is replaced by other amino acids inhibited the activity of the catalytic subunit of cyclic AMP-dependent protein kinase from beef skeletal muscle (Peak I). All of the analogues were competitive with respect to peptide substrate but apparent Ki values varied depending on the particular amino acid that was substituted for serine. Inhibition was also competitive with respect to mixed histone as determined in experiments utilizing one of the analogues. Acetylation of the terminal amino group of Leu-Arg-Arg-Ala-Ser-Leu-Gly lowered the Km for this substrate from 16 micrometer to 3 micrometer, but a similar modification of the inhibitory analogue Leu-Arg-Arg-Ala-Ala-Leu-Gly resulted in no major change in the Ki value. An amount of inhibitory peptide sufficient to inhibit the cyclic AMP-dependent protein kinase by 90% caused less than 10% inhibition of several cyclic AMP-independent protein kinases indicating a high degree of specificity of inhibition by the peptide analogues. The experiments show that synthetic peptide analogues could be useful in identifying phosphorylation reactions catalyzed by cyclic AMP-dependent protein kinase as distinguished from other protein kinase reactions.", "contents": "Inhibition of cyclic AMP-dependent protein kinase by analogues of a synthetic peptide substrate. Analogues of the synthetic substrate Leu-Arg-Arg-Ala-Ser-Leu-Gly in which the serine is replaced by other amino acids inhibited the activity of the catalytic subunit of cyclic AMP-dependent protein kinase from beef skeletal muscle (Peak I). All of the analogues were competitive with respect to peptide substrate but apparent Ki values varied depending on the particular amino acid that was substituted for serine. Inhibition was also competitive with respect to mixed histone as determined in experiments utilizing one of the analogues. Acetylation of the terminal amino group of Leu-Arg-Arg-Ala-Ser-Leu-Gly lowered the Km for this substrate from 16 micrometer to 3 micrometer, but a similar modification of the inhibitory analogue Leu-Arg-Arg-Ala-Ala-Leu-Gly resulted in no major change in the Ki value. An amount of inhibitory peptide sufficient to inhibit the cyclic AMP-dependent protein kinase by 90% caused less than 10% inhibition of several cyclic AMP-independent protein kinases indicating a high degree of specificity of inhibition by the peptide analogues. The experiments show that synthetic peptide analogues could be useful in identifying phosphorylation reactions catalyzed by cyclic AMP-dependent protein kinase as distinguished from other protein kinase reactions."}
{"id": "PMID:214439", "title": "Role of lysine residues of plasma lipoproteins in high affinity binding to cell surface receptors on human fibroblasts.", "content": "The low density lipoprotein (LDL) cell surface receptors on human fibroblasts grown in culture bind specific plasma lipoproteins, initiating a series of events which regulate intracellular cholesterol metabolism. Specificity for the interaction with the receptors resides with the protein moieties of the lipoproteins, specifically with the B and E apoproteins of LDL and certain high density lipoproteins (HDLc HDLl), respectively. It was previously established that the amino acid arginine is a functionally significant residue in or near the recognition sites on the B and E apoproteins and that modification of this residue abolishes the ability of these apolipoproteins to bind to the receptor. The present study indicates that lysine residues are also involved in the lipoprotein-receptor interaction. Chemical modification of 15% of the lysine residues of LDL by carbamylation with cyanate or 20% by acetoacetylation with diketene prevents the LDL from competitively displacing unmodified 125I-LDL from the high affinity receptor sites or from binding directly to the receptor. Moreover, quantitative reversal of the aceto-acetylation of the lysine residues of LDL by hydroxylamine treatment regenerates the lysyl residues and reestablishes greater than 90% of the original binding activity of the LDL. The reversibility of this reaction establishes that the loss of binding activity which follows lysine modification is not due to an irreversible alteration of the LDL or HDLc but is probably due to an alteration of a property of the recognition site associated with specific lysine residues. While acetoacetylation and carbamylation neutralize the positive charge on the epsilon-amino group of lysine, reductive methylation selectively modifies lysine residues of LDL and HDLc without altering the positive charge, yet abolishes their ability to bind to the receptor. Preservation of the charge but loss of binding activity following reductive methylation of the lipoproteins suggests that the specificity of the recognition site does not reside simply with the presence of positive charges but depends on other more specific properties of the site determined by the presence of a limited number of the lysine (and arginine) residues. The precise role of lysine remains to be defined, but its function may be to establish and maintain the conformation of the recognition site or the alignment of reactive residues, or both, or to chemically react, through its epsilon-amino group, with the receptor (hydrogen bond formation would be such a possibility).", "contents": "Role of lysine residues of plasma lipoproteins in high affinity binding to cell surface receptors on human fibroblasts. The low density lipoprotein (LDL) cell surface receptors on human fibroblasts grown in culture bind specific plasma lipoproteins, initiating a series of events which regulate intracellular cholesterol metabolism. Specificity for the interaction with the receptors resides with the protein moieties of the lipoproteins, specifically with the B and E apoproteins of LDL and certain high density lipoproteins (HDLc HDLl), respectively. It was previously established that the amino acid arginine is a functionally significant residue in or near the recognition sites on the B and E apoproteins and that modification of this residue abolishes the ability of these apolipoproteins to bind to the receptor. The present study indicates that lysine residues are also involved in the lipoprotein-receptor interaction. Chemical modification of 15% of the lysine residues of LDL by carbamylation with cyanate or 20% by acetoacetylation with diketene prevents the LDL from competitively displacing unmodified 125I-LDL from the high affinity receptor sites or from binding directly to the receptor. Moreover, quantitative reversal of the aceto-acetylation of the lysine residues of LDL by hydroxylamine treatment regenerates the lysyl residues and reestablishes greater than 90% of the original binding activity of the LDL. The reversibility of this reaction establishes that the loss of binding activity which follows lysine modification is not due to an irreversible alteration of the LDL or HDLc but is probably due to an alteration of a property of the recognition site associated with specific lysine residues. While acetoacetylation and carbamylation neutralize the positive charge on the epsilon-amino group of lysine, reductive methylation selectively modifies lysine residues of LDL and HDLc without altering the positive charge, yet abolishes their ability to bind to the receptor. Preservation of the charge but loss of binding activity following reductive methylation of the lipoproteins suggests that the specificity of the recognition site does not reside simply with the presence of positive charges but depends on other more specific properties of the site determined by the presence of a limited number of the lysine (and arginine) residues. The precise role of lysine remains to be defined, but its function may be to establish and maintain the conformation of the recognition site or the alignment of reactive residues, or both, or to chemically react, through its epsilon-amino group, with the receptor (hydrogen bond formation would be such a possibility)."}
{"id": "PMID:214440", "title": "A latent adenosine triphosphatase form of dynein 1 from sea urchin sperm flagella.", "content": "Treatment of demembranated sea urchin sperm axonemes with an extraction solution containing 0.6 M NaCl, pH 7.0 for 10 min at 4 degrees C yields a solution of dynein 1 having a low, latent specific ATPase activity of about 0.25 mumol of Pi mg(-1) min(-1). Exposure of this dynein solution to 0.1% Triton-X-100 for 10 min at 25 degrees C causes an increase in its ATPase activity to about 3 mumol of Pi mg(-1) min(-1). A similar activation can be obtained by treating at 42 degrees C or by reacting with 60 mol of p-chloromercuribenzene sulfonate/10(6) g of protein. The effects of these activating procedures are not additive, suggesting that they lead to a common activated state. Purification of the latent activity dynein 1 by sucrose density gradient centrifugation yields a monodisperse preparation sedimenting at 21 S, and having a molecular weight of 1,250,000 as determined by sedimentation diffusion and sedimentation equilibrium. Activation of the latent dynein 1 with Triton X-100 converts it to a form sedimenting at 10 to 14 S. The 21 S dynein is also converted to a 10 S form by dialysis against 5 mM imidazole/NaOH buffer, 0.1 mM EDTA, 5 mM 2-mercaptoethanol, pH 7, although in this case, the ATPase activity is increased only about 3-fold, with another 3-fold activation being obtainable upon subsequent treatment with Triton X-100. The 21 S latent form of dynein 1 may represent the intact dynein arms that form moving cross-bridges and generate active sliding between adjacent doublet tubules of the flagellar axoneme. Electrophoretic analysis on polyacrylamide gels in the presence of sodium dodecyl sulfate suggests a model in which the 21 S dynein 1 particle is composed of three subunits of about 330,000 daltons and one of each of three medium weight subunits of 126,000, 95,000, and 77,000 daltons. When latent dynein 1 is added back to NaCl-extracted axonemes in the presence of 0.15 M NaCl, it recombines stoichiometrically and restores the arms on the doublet tubules with a 6-fold activation of its ATPase activity measured in the absence of KCl.", "contents": "A latent adenosine triphosphatase form of dynein 1 from sea urchin sperm flagella. Treatment of demembranated sea urchin sperm axonemes with an extraction solution containing 0.6 M NaCl, pH 7.0 for 10 min at 4 degrees C yields a solution of dynein 1 having a low, latent specific ATPase activity of about 0.25 mumol of Pi mg(-1) min(-1). Exposure of this dynein solution to 0.1% Triton-X-100 for 10 min at 25 degrees C causes an increase in its ATPase activity to about 3 mumol of Pi mg(-1) min(-1). A similar activation can be obtained by treating at 42 degrees C or by reacting with 60 mol of p-chloromercuribenzene sulfonate/10(6) g of protein. The effects of these activating procedures are not additive, suggesting that they lead to a common activated state. Purification of the latent activity dynein 1 by sucrose density gradient centrifugation yields a monodisperse preparation sedimenting at 21 S, and having a molecular weight of 1,250,000 as determined by sedimentation diffusion and sedimentation equilibrium. Activation of the latent dynein 1 with Triton X-100 converts it to a form sedimenting at 10 to 14 S. The 21 S dynein is also converted to a 10 S form by dialysis against 5 mM imidazole/NaOH buffer, 0.1 mM EDTA, 5 mM 2-mercaptoethanol, pH 7, although in this case, the ATPase activity is increased only about 3-fold, with another 3-fold activation being obtainable upon subsequent treatment with Triton X-100. The 21 S latent form of dynein 1 may represent the intact dynein arms that form moving cross-bridges and generate active sliding between adjacent doublet tubules of the flagellar axoneme. Electrophoretic analysis on polyacrylamide gels in the presence of sodium dodecyl sulfate suggests a model in which the 21 S dynein 1 particle is composed of three subunits of about 330,000 daltons and one of each of three medium weight subunits of 126,000, 95,000, and 77,000 daltons. When latent dynein 1 is added back to NaCl-extracted axonemes in the presence of 0.15 M NaCl, it recombines stoichiometrically and restores the arms on the doublet tubules with a 6-fold activation of its ATPase activity measured in the absence of KCl."}
{"id": "PMID:214443", "title": "Induction of metabolic changes and down regulation of bovine parathyroid hormone-responsive adenylate cyclase are dissociable in isolated osteoclastic and osteoblastic bone cells.", "content": "Bovine parathyroid hormone (PTH), dibutyryl cAMP, and calcium each induce similar metabolic changes in isolated bone cells. PTH and calcium, but not dibutyryl cAMP, result in desensitization of osteoclastic and osteoblastic bone cells to PTH. In osteoblastic cells, calcium effects are specific for PTH receptor.adenylate cyclase complexes and responsiveness to other hormones is not reduced while in osteoclastic cells, small effects of high calcium on prostaglandin E1- and epinephrine-inducible cAMP accompany the large decreases seen in cAMP response to PTH. The membrane effects of calcium and of PTH appear to be independently regulated as PTH-induced desensitization can be initiated in the absence of calcium. In addition, calcium effects on PTH-sensitive adenylate cyclase follow a different calcium dose-response than PTH-like metabolic changes. These results suggest that the effect of calcium on the membrane is not directly related to its induction of PTH-like metabolic changes. A possible role of calcium as an in vivo regulator of bone cell sensitivity to PTH is discussed.", "contents": "Induction of metabolic changes and down regulation of bovine parathyroid hormone-responsive adenylate cyclase are dissociable in isolated osteoclastic and osteoblastic bone cells. Bovine parathyroid hormone (PTH), dibutyryl cAMP, and calcium each induce similar metabolic changes in isolated bone cells. PTH and calcium, but not dibutyryl cAMP, result in desensitization of osteoclastic and osteoblastic bone cells to PTH. In osteoblastic cells, calcium effects are specific for PTH receptor.adenylate cyclase complexes and responsiveness to other hormones is not reduced while in osteoclastic cells, small effects of high calcium on prostaglandin E1- and epinephrine-inducible cAMP accompany the large decreases seen in cAMP response to PTH. The membrane effects of calcium and of PTH appear to be independently regulated as PTH-induced desensitization can be initiated in the absence of calcium. In addition, calcium effects on PTH-sensitive adenylate cyclase follow a different calcium dose-response than PTH-like metabolic changes. These results suggest that the effect of calcium on the membrane is not directly related to its induction of PTH-like metabolic changes. A possible role of calcium as an in vivo regulator of bone cell sensitivity to PTH is discussed."}
{"id": "PMID:214444", "title": "Isoproterenol-induced desensitization of adenylate cyclase in human astrocytoma cells. Relation of loss of hormonal responsiveness and decrement in beta-adrenergic receptors.", "content": "Incubation of human astrocytoma cells (1321N1) with low concentrations of isoproterenol results in a specific loss of responsiveness to catecholamines as evidenced by a decreased accumulation of cAMP in intact cells, a reduction in isoproterenol-stimulated adenylate cyclase activity, and a decrease in beta-adrenergic receptor density, as measured by the specific binding of 125I-hydroxybenzylpindolol. The kinetics of desensitization suggest the involvement of two different reactions. The initial reaction involves a rapid loss of adenylate cyclase activity with little loss of beta-adrenergic receptors. Subsequently, a slower reaction results in the loss of measurable beta-adrenergic receptors. The degree of loss of both parameters was similar after 24 h of desensitization. It is concluded that the loss of beta-adrenergic receptors is an event that occurs as a result of the initial uncoupling of the beta-receptor-linked adenylate cyclase.", "contents": "Isoproterenol-induced desensitization of adenylate cyclase in human astrocytoma cells. Relation of loss of hormonal responsiveness and decrement in beta-adrenergic receptors. Incubation of human astrocytoma cells (1321N1) with low concentrations of isoproterenol results in a specific loss of responsiveness to catecholamines as evidenced by a decreased accumulation of cAMP in intact cells, a reduction in isoproterenol-stimulated adenylate cyclase activity, and a decrease in beta-adrenergic receptor density, as measured by the specific binding of 125I-hydroxybenzylpindolol. The kinetics of desensitization suggest the involvement of two different reactions. The initial reaction involves a rapid loss of adenylate cyclase activity with little loss of beta-adrenergic receptors. Subsequently, a slower reaction results in the loss of measurable beta-adrenergic receptors. The degree of loss of both parameters was similar after 24 h of desensitization. It is concluded that the loss of beta-adrenergic receptors is an event that occurs as a result of the initial uncoupling of the beta-receptor-linked adenylate cyclase."}
{"id": "PMID:214445", "title": "Evidence in intact cells for an involvement of GTP in the activation of adenylate cyclase.", "content": "Treatment of cultured normal rat kidney cells with virazole or mycophenolic acid which are inhibitors of IMP dehydrogenase decreases by 50 to 70% the ability of prostaglandin E1 or isoproterenol to elevate cAMP levels. Inhibition is maximal by 2 h. The response to cholera toxin is not significantly decreased. Basal cAMP is not affected. Under these conditions, GTP is decreased by 80%, ATP is only 10 to 15% decreased, and UTP and CTP are slightly increased. Normal GTP levels and the responses to prostaglandin E1 and isoproterenol are restored if guanosine, but not inosine, is added with the inhibitor. The response to isoproterenol is recovered within 5 min after removal of mycophenolic acid. Desensitization to prostaglandin E1 or isoproterenol stimulation occurs under conditions where GTP is 80% decreased. These results in intact cells provide direct evidence for a role for GTP in the activation of adenylate cyclase and support previous conclusions from studies with cell homogenates.", "contents": "Evidence in intact cells for an involvement of GTP in the activation of adenylate cyclase. Treatment of cultured normal rat kidney cells with virazole or mycophenolic acid which are inhibitors of IMP dehydrogenase decreases by 50 to 70% the ability of prostaglandin E1 or isoproterenol to elevate cAMP levels. Inhibition is maximal by 2 h. The response to cholera toxin is not significantly decreased. Basal cAMP is not affected. Under these conditions, GTP is decreased by 80%, ATP is only 10 to 15% decreased, and UTP and CTP are slightly increased. Normal GTP levels and the responses to prostaglandin E1 and isoproterenol are restored if guanosine, but not inosine, is added with the inhibitor. The response to isoproterenol is recovered within 5 min after removal of mycophenolic acid. Desensitization to prostaglandin E1 or isoproterenol stimulation occurs under conditions where GTP is 80% decreased. These results in intact cells provide direct evidence for a role for GTP in the activation of adenylate cyclase and support previous conclusions from studies with cell homogenates."}
{"id": "PMID:214448", "title": "Radiologic findings in nasopharyngeal angiofibromas.", "content": "Juvenile nasopharyngeal angiofibromas produce radiographic changes which are sufficiently characteristic to render a diagnosis without resorting to biopsy. Computed tomography is also of value, particularly in following the response of these tumors to therapeutic irreadiation.", "contents": "Radiologic findings in nasopharyngeal angiofibromas. Juvenile nasopharyngeal angiofibromas produce radiographic changes which are sufficiently characteristic to render a diagnosis without resorting to biopsy. Computed tomography is also of value, particularly in following the response of these tumors to therapeutic irreadiation."}
{"id": "PMID:214449", "title": "Tracheal histiocytoma: an inflammatory pseudotumor.", "content": "A tracheal histiocytoma produced airway obstruction in a child. These lesions contain histiocytic, fibrous, and xanthomatous elements and represent benign post-inflammatory reactions without predisposition to malignancy. Treatment is conservative surgical excision.", "contents": "Tracheal histiocytoma: an inflammatory pseudotumor. A tracheal histiocytoma produced airway obstruction in a child. These lesions contain histiocytic, fibrous, and xanthomatous elements and represent benign post-inflammatory reactions without predisposition to malignancy. Treatment is conservative surgical excision."}
{"id": "PMID:214450", "title": "Endoplasmic reticulum marker enzymes in Golgi fractions--what does this mean?", "content": "NADPH cytochrome c (cyt c) reductase and glucose-6-phosphatase, two enzymes thought to be restricted to the endoplasmic reticulum (ER) and widely used as ER markers, are present in isolated Golgi fractions assayed immediately after their isolation. Both enzymes are rapidly inactivated in fractions stored at 0 degrees C in 0.25 M sucrose, conditions which do not affect the activity of other enzymes in the same preparation. The inactivation process was shown to be dependent on time and protein concentration and could be prevented by EDTA and catalase. Morphological evidence shows that extensive membrane damage occurs parallel with the inactivation. Taken together with the immunological data in the companion paper, the findings indicate that the enzymes NADPH cyt c reductase and probably glucose-6-phosphate are indigenous components of Golgi membranes.", "contents": "Endoplasmic reticulum marker enzymes in Golgi fractions--what does this mean? NADPH cytochrome c (cyt c) reductase and glucose-6-phosphatase, two enzymes thought to be restricted to the endoplasmic reticulum (ER) and widely used as ER markers, are present in isolated Golgi fractions assayed immediately after their isolation. Both enzymes are rapidly inactivated in fractions stored at 0 degrees C in 0.25 M sucrose, conditions which do not affect the activity of other enzymes in the same preparation. The inactivation process was shown to be dependent on time and protein concentration and could be prevented by EDTA and catalase. Morphological evidence shows that extensive membrane damage occurs parallel with the inactivation. Taken together with the immunological data in the companion paper, the findings indicate that the enzymes NADPH cyt c reductase and probably glucose-6-phosphate are indigenous components of Golgi membranes."}
{"id": "PMID:214451", "title": "Presence of NADPH-cytochrome P-450 reductase in rat liver Golgi membranes. Evidence obtained by immunoadsorption method.", "content": "Light Golgi fractions (GF(1+2)) prepared from rat liver homogenates by a modification of the Ehrenreich et al. procedure (J. Cell Biol. 59:45) had significant NADPH-cytochrome P(450) reductase (NADPH-cyt c reductase) activity if assayed immediately after their isolation. An antibody raised in rabbits against purified microsomal and Golgi fractions. To find out whether this activity is located in bona fide Golgi elements or in contaminating microsomal vesicles, we used the following 3-step immunoadsorption procedure: (a) antirabbit IgG (raised in goats) was conjugated to small (2-5 mum) polycrylamide (PA) beads; (b) rabbit anti NADPH-cyt c reductase was immunoadsorbed to the antibody-coated beads; and (c) GF(1+2) was reacted with the beads carrying the two successive layers of antibodies. The beads were then recovered by centrifugation, and were washed, fixed, embedded in agarose, and processed for transmission electromicroscopy. Antireductase- coated beads absorbed 60 percent of the NADPH-cyt c reductase (and comparable fractions of NADH-cyt c reductase and glucose-6-phosphatase) but only 20 percent of the galactosyltransferase activity of the input GF(1+2). Differential vesicle counts showed that approximately 72 percent of the immunoadsorbed vesicles were morphologically recognizable Golgi elements (vesicles with very low density lipoprotein [VLDL] clusters or Golgi cisternae); vesicles with single VLDL and smooth surfaced microsome-like vesicles were too few (approximately 25 percent) to account for the activity. It is concluded that NADPH-cytochrome P(450) reductase is a Golgi membrane enzyme of probably uneven distribution among the elements of the Golgi complex.", "contents": "Presence of NADPH-cytochrome P-450 reductase in rat liver Golgi membranes. Evidence obtained by immunoadsorption method. Light Golgi fractions (GF(1+2)) prepared from rat liver homogenates by a modification of the Ehrenreich et al. procedure (J. Cell Biol. 59:45) had significant NADPH-cytochrome P(450) reductase (NADPH-cyt c reductase) activity if assayed immediately after their isolation. An antibody raised in rabbits against purified microsomal and Golgi fractions. To find out whether this activity is located in bona fide Golgi elements or in contaminating microsomal vesicles, we used the following 3-step immunoadsorption procedure: (a) antirabbit IgG (raised in goats) was conjugated to small (2-5 mum) polycrylamide (PA) beads; (b) rabbit anti NADPH-cyt c reductase was immunoadsorbed to the antibody-coated beads; and (c) GF(1+2) was reacted with the beads carrying the two successive layers of antibodies. The beads were then recovered by centrifugation, and were washed, fixed, embedded in agarose, and processed for transmission electromicroscopy. Antireductase- coated beads absorbed 60 percent of the NADPH-cyt c reductase (and comparable fractions of NADH-cyt c reductase and glucose-6-phosphatase) but only 20 percent of the galactosyltransferase activity of the input GF(1+2). Differential vesicle counts showed that approximately 72 percent of the immunoadsorbed vesicles were morphologically recognizable Golgi elements (vesicles with very low density lipoprotein [VLDL] clusters or Golgi cisternae); vesicles with single VLDL and smooth surfaced microsome-like vesicles were too few (approximately 25 percent) to account for the activity. It is concluded that NADPH-cytochrome P(450) reductase is a Golgi membrane enzyme of probably uneven distribution among the elements of the Golgi complex."}
{"id": "PMID:214452", "title": "Computer simulation of aggregation in Dictyostelium discoideum.", "content": "The aggregation phase of development of the cellular slime mould Dictyostelium discoideum is simulated on a computer. The simulation is performed in 2 dimensions, and produces animated graphical output similar to time-lapse films. It is based on observations of cell behaviour as expressed by a set of rules for each cell, involving cell movement and release of and response to chemical signals. Following these rules, the simulation has reproduced many observed aggregation patterns: propagating waves of cell movement; formation of branching streams; entrainment of slower centres; and spiral centre formation. The simulation has proved to be an important adjunct to experimental work.", "contents": "Computer simulation of aggregation in Dictyostelium discoideum. The aggregation phase of development of the cellular slime mould Dictyostelium discoideum is simulated on a computer. The simulation is performed in 2 dimensions, and produces animated graphical output similar to time-lapse films. It is based on observations of cell behaviour as expressed by a set of rules for each cell, involving cell movement and release of and response to chemical signals. Following these rules, the simulation has reproduced many observed aggregation patterns: propagating waves of cell movement; formation of branching streams; entrainment of slower centres; and spiral centre formation. The simulation has proved to be an important adjunct to experimental work."}
{"id": "PMID:214453", "title": "SV40-transformed hamster cells resistant to 100--250 microgram/ml of ethidium bromide.", "content": "SV40-transformed hamster cells were selected for resistance to ethidium bromide (EB). Several cell lines were established, which grew in the presence of up to 250 microgram/ml EB. The EB resistance is genetically stable. The cloned resistant cells show no difference in morphology, with the exception of the mitochondrial ultrastructure, which exhibits condensed cristae formation. The tumorigenicity of these cells in Syrian gold hamsters is considerably reduced. Incorporation of radioactive labelled thymidine into mitochondrial DNA is not influenced by the presence of the drug. Gel electrophoresis with mitochondrial proteins from wild-type and resistant cells reveals significantly different patterns. The mechanism of EB resistance is discussed.", "contents": "SV40-transformed hamster cells resistant to 100--250 microgram/ml of ethidium bromide. SV40-transformed hamster cells were selected for resistance to ethidium bromide (EB). Several cell lines were established, which grew in the presence of up to 250 microgram/ml EB. The EB resistance is genetically stable. The cloned resistant cells show no difference in morphology, with the exception of the mitochondrial ultrastructure, which exhibits condensed cristae formation. The tumorigenicity of these cells in Syrian gold hamsters is considerably reduced. Incorporation of radioactive labelled thymidine into mitochondrial DNA is not influenced by the presence of the drug. Gel electrophoresis with mitochondrial proteins from wild-type and resistant cells reveals significantly different patterns. The mechanism of EB resistance is discussed."}
{"id": "PMID:214454", "title": "Stimulation of dendritogenesis in the epidermal melanocytes of newborn mice by melanocyte-stimulating hormone.", "content": "The number of dendrites and the total length of dendrites in the epidermal melanocytes positive for the dopa reaction were shown to increase when newborn mice were injected with alpha-MSH or DBc-AMP. Moreover, both indices of the degree of dendritogenesis increased when skin explants of newborn mice were cultured in medium containing alpha-MSH or DBc-AMP. Electron-microscopic observation showed that the number of melanosomes was also increased by alpha-MSH treatment. Many mature melanosomes were observed in the dendrites of the epidermal melanocytes of alpha-MSH-injected mice. Highly dendritic melanocytes seem to be the cells stimulated by MSH to form melanosomes and translocate them to dendrites. Dendritogenesis stimulated by the hormone was suppressed by actinomycin D or cycloheximide, suggesting that the dendritogenesis in the epidermal melanocytes requires de novo transcription and translation.", "contents": "Stimulation of dendritogenesis in the epidermal melanocytes of newborn mice by melanocyte-stimulating hormone. The number of dendrites and the total length of dendrites in the epidermal melanocytes positive for the dopa reaction were shown to increase when newborn mice were injected with alpha-MSH or DBc-AMP. Moreover, both indices of the degree of dendritogenesis increased when skin explants of newborn mice were cultured in medium containing alpha-MSH or DBc-AMP. Electron-microscopic observation showed that the number of melanosomes was also increased by alpha-MSH treatment. Many mature melanosomes were observed in the dendrites of the epidermal melanocytes of alpha-MSH-injected mice. Highly dendritic melanocytes seem to be the cells stimulated by MSH to form melanosomes and translocate them to dendrites. Dendritogenesis stimulated by the hormone was suppressed by actinomycin D or cycloheximide, suggesting that the dendritogenesis in the epidermal melanocytes requires de novo transcription and translation."}
{"id": "PMID:214455", "title": "Contact behaviour and pattern formation of BHK and polyoma virus-transformed BHK fibroblasts in culture.", "content": "Certain behavioural and morphological aspects of cellular transformation have been studied, using baby hamster kidney cells (BHK21/13) and polyoma virus-transformed BHK cells. BHK cellsgrow to monolayer arranged in parallel arrays, whereas the transformed cells show a much greater incidence of crisscrossing and multilayering. Time-lapse cinemicrography and scanning electron microscopy were used to examine the behaviour producing these striking differences in cellular pattern. It was found, contrary to previous thought, that in both cell lines, when contact is made ruffle to ruffle, ruffling is inhibited. When BHK cell contact each other ruffle to side, strong adhesions always occur, as evidence by a large deformation of the contacted cell margin, with accompanying paralysis of ruffling. Then, the contacting cell either changes direction, usually spreading along the side of the contacted cell, or occasionally continues to protrude and underlap the other cell, although the original adhesions are seen to remain. Transformed cells never form strong ruffle-to-side adhesions, and usually underlap each other totally. When the cells were filmed, fixed and the same cells relocated in the scanning electron microscope, neither cell type was seen to move over the surface of another (overlap). Rather, all cells crisscross by underlapping (moving under the other cell). SEM also reveals PyBHK cells to have many fewer side-to-substratum adhesions than BHK cells. The smaller number of these attachments could explain the ease with which PyBHK cells underlap.", "contents": "Contact behaviour and pattern formation of BHK and polyoma virus-transformed BHK fibroblasts in culture. Certain behavioural and morphological aspects of cellular transformation have been studied, using baby hamster kidney cells (BHK21/13) and polyoma virus-transformed BHK cells. BHK cellsgrow to monolayer arranged in parallel arrays, whereas the transformed cells show a much greater incidence of crisscrossing and multilayering. Time-lapse cinemicrography and scanning electron microscopy were used to examine the behaviour producing these striking differences in cellular pattern. It was found, contrary to previous thought, that in both cell lines, when contact is made ruffle to ruffle, ruffling is inhibited. When BHK cell contact each other ruffle to side, strong adhesions always occur, as evidence by a large deformation of the contacted cell margin, with accompanying paralysis of ruffling. Then, the contacting cell either changes direction, usually spreading along the side of the contacted cell, or occasionally continues to protrude and underlap the other cell, although the original adhesions are seen to remain. Transformed cells never form strong ruffle-to-side adhesions, and usually underlap each other totally. When the cells were filmed, fixed and the same cells relocated in the scanning electron microscope, neither cell type was seen to move over the surface of another (overlap). Rather, all cells crisscross by underlapping (moving under the other cell). SEM also reveals PyBHK cells to have many fewer side-to-substratum adhesions than BHK cells. The smaller number of these attachments could explain the ease with which PyBHK cells underlap."}
{"id": "PMID:214456", "title": "Plastic multiwell plates to assay avian infectious bronchitis virus in organ cultures of chicken embryo trachea.", "content": "Simple assay systems for infectivity titrations of avian infectious bronchitis virus (IBV) in chicken embryo trachea organ cultures (OC) were developed using plastic multiplate wells with one tracheal ring per well; these assays appeared to be much more satisfactory than the conventional rolled-tube method. The medium, 0.05 M HEPES (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid)-buffered Eagle minimal essential medium was not changed during observation. A medium containing 0.4% bovine serum albumin did not influence the virus yield, but did stabilize virus viability during storage. Reproducibility of results obtained in the OC system was confirmed by performing replicate titrations of the Beaudette strain with three different passage histories. The mean virus titers in the OC were lower than those in chicken embryos, depending on the IBV passage histories. The time required for ciliostasis was related not only to the concentration of virus, but also to the IBV passage history. Application of OC techniques for the constant serum-variable virus neutralization test gave low neutralization indexes with excellent reproducibility as compared with those obtained in the chicken embryo assay system. Also, the slopes of neutralization curves obtained by assays in OC were less steep than those seen in the chicken embryo system.", "contents": "Plastic multiwell plates to assay avian infectious bronchitis virus in organ cultures of chicken embryo trachea. Simple assay systems for infectivity titrations of avian infectious bronchitis virus (IBV) in chicken embryo trachea organ cultures (OC) were developed using plastic multiplate wells with one tracheal ring per well; these assays appeared to be much more satisfactory than the conventional rolled-tube method. The medium, 0.05 M HEPES (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid)-buffered Eagle minimal essential medium was not changed during observation. A medium containing 0.4% bovine serum albumin did not influence the virus yield, but did stabilize virus viability during storage. Reproducibility of results obtained in the OC system was confirmed by performing replicate titrations of the Beaudette strain with three different passage histories. The mean virus titers in the OC were lower than those in chicken embryos, depending on the IBV passage histories. The time required for ciliostasis was related not only to the concentration of virus, but also to the IBV passage history. Application of OC techniques for the constant serum-variable virus neutralization test gave low neutralization indexes with excellent reproducibility as compared with those obtained in the chicken embryo assay system. Also, the slopes of neutralization curves obtained by assays in OC were less steep than those seen in the chicken embryo system."}
{"id": "PMID:214457", "title": "Center for Disease Control Diagnostic Immunology Proficiency Testing Program results for 1977.", "content": "A summary of the yearly data accumulated and analyzed in the diagnostic immunology portion of the Center for Disease Control 1977 Proficiency Testing Program provides information on the trends in testing protocols from over 900 participating laboratories. One hundred and fourteen specimens prepared by the Center for the Disease Control were distributed quarterly or in special surveys. The specimens chosen provided feedback from a broad range of tests commonly performed in diagnostic immunology laboratories and included those for rubella antibodies, hepatitis B surface antigen, bacterial antibodies, rheumatoid factor, immunoglobulins and other serum-specific proteins, syphilis serology, and carcinoembryonic antigen. This summary provides an overview of the trends observed since last year's report.", "contents": "Center for Disease Control Diagnostic Immunology Proficiency Testing Program results for 1977. A summary of the yearly data accumulated and analyzed in the diagnostic immunology portion of the Center for Disease Control 1977 Proficiency Testing Program provides information on the trends in testing protocols from over 900 participating laboratories. One hundred and fourteen specimens prepared by the Center for the Disease Control were distributed quarterly or in special surveys. The specimens chosen provided feedback from a broad range of tests commonly performed in diagnostic immunology laboratories and included those for rubella antibodies, hepatitis B surface antigen, bacterial antibodies, rheumatoid factor, immunoglobulins and other serum-specific proteins, syphilis serology, and carcinoembryonic antigen. This summary provides an overview of the trends observed since last year's report."}
{"id": "PMID:214458", "title": "Role of rotavirus (reo-like) in weanling diarrhea of pigs.", "content": "Piglets weaned abruptly and precociously at 3 weeks of age and placed in a crowded nursery commenced diarrhea 3 to 5 days later. Death losses were low (approximately 6%), but weight gain ceased for 2 weeks. Large numbers of rotavirus (reo-like) particles were seen by electron microscopy in diarrhetic fluids. Sections of intestines showed a loss of adsorptive surface in that villi were shortened and fused with adjacent villi. Immunofluorescence revealed rotaviral antigens within damaged enterocytes. Rotavirus-containing gut fluid was harvested from sick, weaned piglets. This fluid, filtered free of bacteria, was used to inoculate per os colostrum-deprived piglets. These infected piglets developed diarrhea and dehydration, and large numbers of rotaviral particles were seen in their diarrhetic fluid. Also, rotaviral antigens were present in aberrant enterocytes, and the intestinal villi were shortened. Since the weaned piglets (3 weeks old) came from sows that were providing their piglet's intestine with passive antibody protection via milk, we concluded that the abrupt removal of the piglet from the gut-bathing antibody combined with the stress of weaning produced a neonate vulnerable to the ubiquitous rotavirus. Similar circumstances may prevail and operate in exacerbating rotaviral diarrhea in neonates of other species of mammals.", "contents": "Role of rotavirus (reo-like) in weanling diarrhea of pigs. Piglets weaned abruptly and precociously at 3 weeks of age and placed in a crowded nursery commenced diarrhea 3 to 5 days later. Death losses were low (approximately 6%), but weight gain ceased for 2 weeks. Large numbers of rotavirus (reo-like) particles were seen by electron microscopy in diarrhetic fluids. Sections of intestines showed a loss of adsorptive surface in that villi were shortened and fused with adjacent villi. Immunofluorescence revealed rotaviral antigens within damaged enterocytes. Rotavirus-containing gut fluid was harvested from sick, weaned piglets. This fluid, filtered free of bacteria, was used to inoculate per os colostrum-deprived piglets. These infected piglets developed diarrhea and dehydration, and large numbers of rotaviral particles were seen in their diarrhetic fluid. Also, rotaviral antigens were present in aberrant enterocytes, and the intestinal villi were shortened. Since the weaned piglets (3 weeks old) came from sows that were providing their piglet's intestine with passive antibody protection via milk, we concluded that the abrupt removal of the piglet from the gut-bathing antibody combined with the stress of weaning produced a neonate vulnerable to the ubiquitous rotavirus. Similar circumstances may prevail and operate in exacerbating rotaviral diarrhea in neonates of other species of mammals."}
{"id": "PMID:214459", "title": "Essential role of GTP in the expression of adenylate cyclase activity after cholera toxin treatment.", "content": "Expression of activation of rat liver adenylate cyclase by the A1 peptide of cholera toxin and NAD is dependent on GTP. The nucleotide is effective either when added to the assay medium or during toxin (and NAD) treatment. Toxin treatment increases the Vmax for activation by GTP and the effect of GTP persists in toxin-treated membranes, a property seen in control membranes only with non-hydrolyzable analogs of GTP such as Gpp(NH)p. These observations could be explained by a recent report that cholera toxin acts to inhibit a GTPase associated with denylate cyclase. However, we have observed that one of the major effects of the toxin is to decrease the affinity of guanine nucleotides for the processes involved in the activation of adenylate cyclase and in the regulation of the binding of glucagon to its receptor. Moreover, the absence of lag time in the activation of adenylate cyclase by GTP, in contrast to by Gpp(NH)p, and the markedly reduced fluoride action after toxin treatment suggest that GTPase inhibition may not be the only action of cholera toxin on the adenylate cyclase system. We believe that the multiple effects of toxin action is a reflection of the recently revealed complexity of the regulation of adenylate cyclase by guanine nucleotides.", "contents": "Essential role of GTP in the expression of adenylate cyclase activity after cholera toxin treatment. Expression of activation of rat liver adenylate cyclase by the A1 peptide of cholera toxin and NAD is dependent on GTP. The nucleotide is effective either when added to the assay medium or during toxin (and NAD) treatment. Toxin treatment increases the Vmax for activation by GTP and the effect of GTP persists in toxin-treated membranes, a property seen in control membranes only with non-hydrolyzable analogs of GTP such as Gpp(NH)p. These observations could be explained by a recent report that cholera toxin acts to inhibit a GTPase associated with denylate cyclase. However, we have observed that one of the major effects of the toxin is to decrease the affinity of guanine nucleotides for the processes involved in the activation of adenylate cyclase and in the regulation of the binding of glucagon to its receptor. Moreover, the absence of lag time in the activation of adenylate cyclase by GTP, in contrast to by Gpp(NH)p, and the markedly reduced fluoride action after toxin treatment suggest that GTPase inhibition may not be the only action of cholera toxin on the adenylate cyclase system. We believe that the multiple effects of toxin action is a reflection of the recently revealed complexity of the regulation of adenylate cyclase by guanine nucleotides."}
{"id": "PMID:214460", "title": "Growth arrest of Chinese hamster ovary cells in serum-free medium: changes in cell morphology and the intracellular and prostaglandin-induced levels of cyclic AMP.", "content": "When Chinese hamster ovary (CHO) cells are shifted from medium which contains serum into serum-free medium, they complete one cell doubling and arrest in the G1 phase of the cell cycle. During the first 72 hr of arrest, there is little change in intracellular adenosine 3':5'-phosphate (cAMP) level, and the cells retain their usual epithelial-like morphology. After 96 hr, the cAMP level doubles, the magnitude of the prostaglandin E1-induced changes in cAMP increases threefold, and the cells convert from a rounded, epithelial-like shape to an elongated, fibroblast-like form. The fact that these biochemical and cellular transitions are subsequent to the growth arrest shows that the cAMP increase is not the cause of the growth arrest but is consistent with a role for cAMP in the control of cell morphology. In addition, these changes point to the importance of the G1 phase for initiating cAMP-related events.", "contents": "Growth arrest of Chinese hamster ovary cells in serum-free medium: changes in cell morphology and the intracellular and prostaglandin-induced levels of cyclic AMP. When Chinese hamster ovary (CHO) cells are shifted from medium which contains serum into serum-free medium, they complete one cell doubling and arrest in the G1 phase of the cell cycle. During the first 72 hr of arrest, there is little change in intracellular adenosine 3':5'-phosphate (cAMP) level, and the cells retain their usual epithelial-like morphology. After 96 hr, the cAMP level doubles, the magnitude of the prostaglandin E1-induced changes in cAMP increases threefold, and the cells convert from a rounded, epithelial-like shape to an elongated, fibroblast-like form. The fact that these biochemical and cellular transitions are subsequent to the growth arrest shows that the cAMP increase is not the cause of the growth arrest but is consistent with a role for cAMP in the control of cell morphology. In addition, these changes point to the importance of the G1 phase for initiating cAMP-related events."}
{"id": "PMID:214461", "title": "S49 lymphoma wild type and variant clones contain normal calcium dependent regulator.", "content": "Calcium dependent regulator is present in wild-type S49 lymphoma cells, in the variant that is deficient in adenylate cyclase activity (AC-), and in the uncoupled variant (UNC). The electrophoretic mobility and the ability to stimulate cyclic nucleotide phosphodiesterase of the calcium dependent regulator from each of these three clones are indistinguishable from those of the modulator protein isolated from bovine brain. Calcium dependent regulator does not appear to be involved in the defect responsible for the UNC or AC- variants.", "contents": "S49 lymphoma wild type and variant clones contain normal calcium dependent regulator. Calcium dependent regulator is present in wild-type S49 lymphoma cells, in the variant that is deficient in adenylate cyclase activity (AC-), and in the uncoupled variant (UNC). The electrophoretic mobility and the ability to stimulate cyclic nucleotide phosphodiesterase of the calcium dependent regulator from each of these three clones are indistinguishable from those of the modulator protein isolated from bovine brain. Calcium dependent regulator does not appear to be involved in the defect responsible for the UNC or AC- variants."}
{"id": "PMID:214462", "title": "Effect of lin-benzoadenosine and lin-benzoadenosine 3':5'-monophosphate on cyclic AMP-dependent protein kinase activity in vitro.", "content": "We have shown that the fluorescent \"stretched-out\" analog of cyclic AMP, namely linear-benzo-cyclic AMP, maximally activates brain protein kinase and protein kinase from skeletal muscle. The corresponding linear-benzoadenosine inhibits kinase activity slightly less than does adenosine. Thus, the 2.4A-wider versions of cyclic AMP and of adenosine interact with protein kinase in a manner similar to that of the natural compounds.", "contents": "Effect of lin-benzoadenosine and lin-benzoadenosine 3':5'-monophosphate on cyclic AMP-dependent protein kinase activity in vitro. We have shown that the fluorescent \"stretched-out\" analog of cyclic AMP, namely linear-benzo-cyclic AMP, maximally activates brain protein kinase and protein kinase from skeletal muscle. The corresponding linear-benzoadenosine inhibits kinase activity slightly less than does adenosine. Thus, the 2.4A-wider versions of cyclic AMP and of adenosine interact with protein kinase in a manner similar to that of the natural compounds."}
{"id": "PMID:214463", "title": "Possible role of cyclic nucleotides in the mechanism of the protective effect of methylprednisolone on the hypoxic rat heart.", "content": "The isolated isovolumic rat heart was used as a model of cardiac hypoxia. Force of cardiac contraction and cardiac cyclic nucleotide levels (cyclic GMP and cyclic AMP) were monitored in hearts subjected to hypoxia for 5 min and allowed to recover by reoxygenation. Hearts were obtained from both control animals and animals pretreated with methylprednisolone at 18 hr and 1 hr prior to sacrifice. Myocardial levels of cyclic GMP which were significantly (p less than 0.05) elevated above control during all periods of hypoxia were found to be lower when hearts were pretreated with methylprednisolone prior to hypoxic exposure. Hearts of animals pretreated with methylprednisolone also demonstrated better recovery during reoxygenation than did control hearts. These studies suggest that methylprednisolone may be beneficial in the prevention of myocardial failure following hypoxia via a modulation in myocardial cyclid GMP content.", "contents": "Possible role of cyclic nucleotides in the mechanism of the protective effect of methylprednisolone on the hypoxic rat heart. The isolated isovolumic rat heart was used as a model of cardiac hypoxia. Force of cardiac contraction and cardiac cyclic nucleotide levels (cyclic GMP and cyclic AMP) were monitored in hearts subjected to hypoxia for 5 min and allowed to recover by reoxygenation. Hearts were obtained from both control animals and animals pretreated with methylprednisolone at 18 hr and 1 hr prior to sacrifice. Myocardial levels of cyclic GMP which were significantly (p less than 0.05) elevated above control during all periods of hypoxia were found to be lower when hearts were pretreated with methylprednisolone prior to hypoxic exposure. Hearts of animals pretreated with methylprednisolone also demonstrated better recovery during reoxygenation than did control hearts. These studies suggest that methylprednisolone may be beneficial in the prevention of myocardial failure following hypoxia via a modulation in myocardial cyclid GMP content."}
{"id": "PMID:214464", "title": "Membrane-bound forms of Ca2+-dependent protein modulator: Ca2+-dependent and independent binding of modulator protein to the particulate fraction from brain.", "content": "Ca2+-dependent binding of modulator protein to the particulate fraction was studied. The particulate fraction from one gram of rat brain bound in a Ca2+-dependent fashion 144 microgram of modulator protein, representing more than one third of the total soluble modulator protein in this tissue. The binding site was present in both the mitochondrial and microsomal fractions, the specific activity of the microsomes being the higher. The binding was reversible with a physiological concentration of Ca2+, and was temperature-dependent, and the site can be saturated with modulator protein (4.5 microgram modulator protein per mg of microsomal protein). Tryptic digestion of the membranes caused complete disappearance of the binding activity, but heat-treatment for 5 min at 70 degrees C caused only 40% loss of activity. The binding site may be a known or unknown enzyme(s), the activity of which is regulated by Ca2+ and modulator. Alternatively, this binding site may be a nonenzymic protein that regulates the concentration of free modulator protein in the cell.", "contents": "Membrane-bound forms of Ca2+-dependent protein modulator: Ca2+-dependent and independent binding of modulator protein to the particulate fraction from brain. Ca2+-dependent binding of modulator protein to the particulate fraction was studied. The particulate fraction from one gram of rat brain bound in a Ca2+-dependent fashion 144 microgram of modulator protein, representing more than one third of the total soluble modulator protein in this tissue. The binding site was present in both the mitochondrial and microsomal fractions, the specific activity of the microsomes being the higher. The binding was reversible with a physiological concentration of Ca2+, and was temperature-dependent, and the site can be saturated with modulator protein (4.5 microgram modulator protein per mg of microsomal protein). Tryptic digestion of the membranes caused complete disappearance of the binding activity, but heat-treatment for 5 min at 70 degrees C caused only 40% loss of activity. The binding site may be a known or unknown enzyme(s), the activity of which is regulated by Ca2+ and modulator. Alternatively, this binding site may be a nonenzymic protein that regulates the concentration of free modulator protein in the cell."}
{"id": "PMID:214465", "title": "A semi quantitative method for cyclic nucleotide localization by immunocytochemistry and its application in determining the distribution of cyclic AMP in lungs of normal and pertussis-vaccinated mice following histamine or epinephrine challenge.", "content": "A method is described which allows quantitative comparison of cAMP content determined by immunocytochemical procedures. This technique was then employed to localize cAMP in lungs of normal and pertussis-vaccinated mice following saline, histamine, or epinephrine challenge. All primary pulmonary compartments were shown to contain some immunoreactive (cAMP) material. However, epinephrine and histamine challenge selectively increased the cAMP content of the vasculature. No effect of epinephrine or histamine was detected in bronchial smooth muscle or interstitial tissue. This increased cAMP accumulation was observed in both normal and pertussis-vaccinated mice following epinephrine challenge but only in pertussis-vaccinated mice after histamine administration. These results demonstrate that histamine and epinephrine stimulate cAMP accumulation in the same pulmonary compartments supporting earlier speculation that histamine acts indirectly through epinephrine release. Further, primary involvement of the vasculature supports a more prominent role for this tissue in pertussis mediated histamine hypersensitivity.", "contents": "A semi quantitative method for cyclic nucleotide localization by immunocytochemistry and its application in determining the distribution of cyclic AMP in lungs of normal and pertussis-vaccinated mice following histamine or epinephrine challenge. A method is described which allows quantitative comparison of cAMP content determined by immunocytochemical procedures. This technique was then employed to localize cAMP in lungs of normal and pertussis-vaccinated mice following saline, histamine, or epinephrine challenge. All primary pulmonary compartments were shown to contain some immunoreactive (cAMP) material. However, epinephrine and histamine challenge selectively increased the cAMP content of the vasculature. No effect of epinephrine or histamine was detected in bronchial smooth muscle or interstitial tissue. This increased cAMP accumulation was observed in both normal and pertussis-vaccinated mice following epinephrine challenge but only in pertussis-vaccinated mice after histamine administration. These results demonstrate that histamine and epinephrine stimulate cAMP accumulation in the same pulmonary compartments supporting earlier speculation that histamine acts indirectly through epinephrine release. Further, primary involvement of the vasculature supports a more prominent role for this tissue in pertussis mediated histamine hypersensitivity."}
{"id": "PMID:214466", "title": "Positive inotropic but no relaxant effects of phenylephrine in cat papillary muscle.", "content": "The effect of phenylephrine (30 micron) in the presence of propranolol (1 micron) on electrically induced isometric twitches and on KCl-contractures was studied in papillary muscles from reserpine-pretreated cats at 25 degrees C. Under these conditions phenylephrine has previously been shown to act solely via alpha-adrenoceptors and not to increase c-AMP. Phenylephrine increased force of contraction, time to peak tension and relaxation time. Contracture tension remained unaffected. These data indicate that the stimulation of cardiac alpha-adrenoceptors, in contrast to beta-adrenergic stimulation, does not lead to so-called relaxant effects. This qualitative difference between the two responses is probably due to the different capacity of both stimuli to increase c-AMP.", "contents": "Positive inotropic but no relaxant effects of phenylephrine in cat papillary muscle. The effect of phenylephrine (30 micron) in the presence of propranolol (1 micron) on electrically induced isometric twitches and on KCl-contractures was studied in papillary muscles from reserpine-pretreated cats at 25 degrees C. Under these conditions phenylephrine has previously been shown to act solely via alpha-adrenoceptors and not to increase c-AMP. Phenylephrine increased force of contraction, time to peak tension and relaxation time. Contracture tension remained unaffected. These data indicate that the stimulation of cardiac alpha-adrenoceptors, in contrast to beta-adrenergic stimulation, does not lead to so-called relaxant effects. This qualitative difference between the two responses is probably due to the different capacity of both stimuli to increase c-AMP."}
{"id": "PMID:214467", "title": "Stimulation of hamster adipocyte cyclic 3':5'-nucleotide phosphodiesterase activity by ionophore A23187 and calcium.", "content": "Incubation of hamster isolated fat cells with the ionophore A23187 and calcium for 20 minutes caused 30-40% increases in the cyclic 3':5'-nucleotide phosphodiesterase (EC 3.1.4.17) activity of adipocyte homogenates when either 0.6 micron cyclic AMP or 0.6 micron cyclic GMP was the enzyme substrate. The stimulation of adipocyte cyclic AMP phosphodiesterase activity by A23187 and calcium was not antagonized by the adrenergic receptor blocking agents phentolamine and propranolol. The changes in enzyme activity produced by the ionophore and calcium were not associated with elevated intracellular cyclic AMP levels. Furthermore, A23187 and calcium acted to enhance adipocyte phosphodiesterase activity before, but not after, homogenization of the fat cells. These data suggest that the phosphodiesterase activity of hamster isolated fat cells may, at least in part, be regulated by fluctuations in intracellular calcium concentrations.", "contents": "Stimulation of hamster adipocyte cyclic 3':5'-nucleotide phosphodiesterase activity by ionophore A23187 and calcium. Incubation of hamster isolated fat cells with the ionophore A23187 and calcium for 20 minutes caused 30-40% increases in the cyclic 3':5'-nucleotide phosphodiesterase (EC 3.1.4.17) activity of adipocyte homogenates when either 0.6 micron cyclic AMP or 0.6 micron cyclic GMP was the enzyme substrate. The stimulation of adipocyte cyclic AMP phosphodiesterase activity by A23187 and calcium was not antagonized by the adrenergic receptor blocking agents phentolamine and propranolol. The changes in enzyme activity produced by the ionophore and calcium were not associated with elevated intracellular cyclic AMP levels. Furthermore, A23187 and calcium acted to enhance adipocyte phosphodiesterase activity before, but not after, homogenization of the fat cells. These data suggest that the phosphodiesterase activity of hamster isolated fat cells may, at least in part, be regulated by fluctuations in intracellular calcium concentrations."}
{"id": "PMID:214468", "title": "Role of cyclic AMP and protein kinase on the steroidogenic action of ACTH, prostaglandin E1 and dibutyryl cyclic AMP in normal adrenal cells and adrenal tumor cells from humans.", "content": "The role of the cyclic AMP-protein kinase system in mediating the steroidogenic effect of ACTH, prostaglandin E1 and dibutyryl cyclic AMP, induced similar stimulations of protein kinase activity, cyclic AMP was studied using human adrenal cells isolated from normal and adrenocortical secreting tumors. At high concentrations of ACTH, complete activation of protein kinase of normal adrenal cells was observed within 3 min, at the time when cyclic AMP production was slightly increased and there was still no stimulation of steroidogenesis. At supramaximal concentrations, ACTH, PGE1 and dibutyryl cyclic AMP and cortisol productions in adrenal cells isolated from normal and from one adrenocortical tumor. In one tumor in which the adenylate cyclase activity was insensitive to ACTH, the hormone was unable to stimulate protein kinase or steroidogenesis, but the cells responded to both PGE1 and dibutyryl cyclic AMP. In another tumor in which the adenylate cyclase was insensitive to PGE1, this compound also did not increase protein kinase activity or steroidogenesis, but both parameters were stimulated by ACTH and dibutyryl cyclic AMP. After incubation of normal adrenal cells with increasing concentrations of ACTH (0.01-100 nM) marked differences were found between cyclic AMP formation and cortisol production. However at the lowest concentrations of ACTH exerting an effect on steroid production a close linked correlation was found between protein kinase activation and cortisol production, but half-maximal and maximal cortisol production occurs at lower concentration of ACTH than was necessary to induce the same stimulation of protein kinase. Similar findings were found after incubating the adrenal cells with dibutyryl cyclic AMP (0.01-10 mM). The results implicate an important role of the cyclic AMP-protein kinase system during activation of adrenal cell steroidogenesis by low concentrations of steroidogenic compounds.", "contents": "Role of cyclic AMP and protein kinase on the steroidogenic action of ACTH, prostaglandin E1 and dibutyryl cyclic AMP in normal adrenal cells and adrenal tumor cells from humans. The role of the cyclic AMP-protein kinase system in mediating the steroidogenic effect of ACTH, prostaglandin E1 and dibutyryl cyclic AMP, induced similar stimulations of protein kinase activity, cyclic AMP was studied using human adrenal cells isolated from normal and adrenocortical secreting tumors. At high concentrations of ACTH, complete activation of protein kinase of normal adrenal cells was observed within 3 min, at the time when cyclic AMP production was slightly increased and there was still no stimulation of steroidogenesis. At supramaximal concentrations, ACTH, PGE1 and dibutyryl cyclic AMP and cortisol productions in adrenal cells isolated from normal and from one adrenocortical tumor. In one tumor in which the adenylate cyclase activity was insensitive to ACTH, the hormone was unable to stimulate protein kinase or steroidogenesis, but the cells responded to both PGE1 and dibutyryl cyclic AMP. In another tumor in which the adenylate cyclase was insensitive to PGE1, this compound also did not increase protein kinase activity or steroidogenesis, but both parameters were stimulated by ACTH and dibutyryl cyclic AMP. After incubation of normal adrenal cells with increasing concentrations of ACTH (0.01-100 nM) marked differences were found between cyclic AMP formation and cortisol production. However at the lowest concentrations of ACTH exerting an effect on steroid production a close linked correlation was found between protein kinase activation and cortisol production, but half-maximal and maximal cortisol production occurs at lower concentration of ACTH than was necessary to induce the same stimulation of protein kinase. Similar findings were found after incubating the adrenal cells with dibutyryl cyclic AMP (0.01-10 mM). The results implicate an important role of the cyclic AMP-protein kinase system during activation of adrenal cell steroidogenesis by low concentrations of steroidogenic compounds."}
{"id": "PMID:214469", "title": "The concentration of cyclic AMP and the activity of cyclic AMP dependent protein kinase and an inhibitor in the adipose tissue of rats fed lard or glucose diets.", "content": "Measurements of tissue cyclic AMP (cAMP) concentration, the activity of cAMP-dependent protein kinase and the level of the enzyme's thermostable, macromolecular inhibitor were made on preparations of rat epididymal fat pad from animals fed high fat or high carbohydrate diets. The cAMP concentration from rats adapted to a high lard diet for 14-15 days was 153 +/- 17.8 pmoles/mg protein as opposed to 76 +/- 6.0 found with high glucose diet. No significant difference in total cAMP-dependent protein kinase activity was observed among rats fed high glucose, high lard or laboratory chow, although the enzyme's activity ratio (-cAMP)(+cAMP) was significantly elevated with lard feeding (0.49 +/- 0.02) as opposed to glucose feeding (0.43 +/- 0.01). Crude preparations from lard and glucose fed animals were equivalent in inhibitory activity when tested with enzyme from chow fed animals. Agarose column chromatography separated holoenzyme and C subunit forms of the protein kinase when 500 mM NaCl was present in the elution buffer. Absence of the salt allowed subunit reassociation to occur. Direct addition of NaCl greater than or equal to 75 mM significantly inhibited protein kinase activity. The results indicate that the adipose tissue of rats fed a high lard diet has a higher concentration of cAMP and an increased protein kinase activity ratio than tissue from rats fed a fat free, high glucose diet. Total cAMP-dependent protein kinase activity and the level of a thermostable macromolecular inhibitor remained unchanged.", "contents": "The concentration of cyclic AMP and the activity of cyclic AMP dependent protein kinase and an inhibitor in the adipose tissue of rats fed lard or glucose diets. Measurements of tissue cyclic AMP (cAMP) concentration, the activity of cAMP-dependent protein kinase and the level of the enzyme's thermostable, macromolecular inhibitor were made on preparations of rat epididymal fat pad from animals fed high fat or high carbohydrate diets. The cAMP concentration from rats adapted to a high lard diet for 14-15 days was 153 +/- 17.8 pmoles/mg protein as opposed to 76 +/- 6.0 found with high glucose diet. No significant difference in total cAMP-dependent protein kinase activity was observed among rats fed high glucose, high lard or laboratory chow, although the enzyme's activity ratio (-cAMP)(+cAMP) was significantly elevated with lard feeding (0.49 +/- 0.02) as opposed to glucose feeding (0.43 +/- 0.01). Crude preparations from lard and glucose fed animals were equivalent in inhibitory activity when tested with enzyme from chow fed animals. Agarose column chromatography separated holoenzyme and C subunit forms of the protein kinase when 500 mM NaCl was present in the elution buffer. Absence of the salt allowed subunit reassociation to occur. Direct addition of NaCl greater than or equal to 75 mM significantly inhibited protein kinase activity. The results indicate that the adipose tissue of rats fed a high lard diet has a higher concentration of cAMP and an increased protein kinase activity ratio than tissue from rats fed a fat free, high glucose diet. Total cAMP-dependent protein kinase activity and the level of a thermostable macromolecular inhibitor remained unchanged."}
{"id": "PMID:214471", "title": "Inhibition of plasminogen activator secretion by cyclic AMP in a macrophage-like cell line.", "content": "The continuous cell line, J774.2, exhibits many macrophage-like functions such as latex and Fc-mediated phagocytosis, antibody mediated phagocytosis, antibody mediated cytotoxicity, chemotaxis, and lysozyme secretion. Cyclic AMP stimulates Fc-mediated phagocytosis and inhibits the growth of J774.2. To further evaluate the relationship between cyclic AMP and the specialized functions exhibited by these cells. Variants deficient in phagocytosis, adenylate cyclase and cyclic AMP-dependent protein kinase were derived. We have now shown that J774.2 also secretes plasminogen activator and that this secretion is rapidly and specifically inhibited by 8-bromoadenosine 3':5'-cyclic monophosphoric acid (8 Br--cAMP) or cholera toxin under conditions where lysozyme secretion is unaltered. Utilizing protein kinase-deficient variants, the ability of cyclic AMP to inhibit plasminogen activator secretion was shown to be mediated by a cyclic AMP-dependent protein kinase. We conclude that cyclic AMP has diametrically opposing effects on two macrophage-like functions: Fc-mediated phagocytosis and plasminogen activator secretion.", "contents": "Inhibition of plasminogen activator secretion by cyclic AMP in a macrophage-like cell line. The continuous cell line, J774.2, exhibits many macrophage-like functions such as latex and Fc-mediated phagocytosis, antibody mediated phagocytosis, antibody mediated cytotoxicity, chemotaxis, and lysozyme secretion. Cyclic AMP stimulates Fc-mediated phagocytosis and inhibits the growth of J774.2. To further evaluate the relationship between cyclic AMP and the specialized functions exhibited by these cells. Variants deficient in phagocytosis, adenylate cyclase and cyclic AMP-dependent protein kinase were derived. We have now shown that J774.2 also secretes plasminogen activator and that this secretion is rapidly and specifically inhibited by 8-bromoadenosine 3':5'-cyclic monophosphoric acid (8 Br--cAMP) or cholera toxin under conditions where lysozyme secretion is unaltered. Utilizing protein kinase-deficient variants, the ability of cyclic AMP to inhibit plasminogen activator secretion was shown to be mediated by a cyclic AMP-dependent protein kinase. We conclude that cyclic AMP has diametrically opposing effects on two macrophage-like functions: Fc-mediated phagocytosis and plasminogen activator secretion."}
{"id": "PMID:214472", "title": "The correlation of cyclic AMP and protein kinase activity in adipocytes with lipolysis stimulated by ACTH: the effect of adenosine deaminase and actinomycin D.", "content": "ACTH at levels as low as 0.05 mU/ml stimulated lipolysis, protein kinase and cyclic AMP accumulation in isolated fat cells from fed and fasted rats. Changes in cyclic AMP levels and in the protein kinase activity ratio were well correlated temporally. The protein kinase activity ratio was potentiated by adenosine deaminase. A sudden increase or decrease in either ACTH or dibutyryl cyclic AMP concentration was associated with a rapid and corresponding change in the rate of glycerol production. With ACTH, the changes in glycerol production were accompanied by appropriate changes in cyclic AMP levels. Actinomycin-D (10 UM) did not affect lipolysis or cyclic AMP accumulation activated by ACTH in fat cells.", "contents": "The correlation of cyclic AMP and protein kinase activity in adipocytes with lipolysis stimulated by ACTH: the effect of adenosine deaminase and actinomycin D. ACTH at levels as low as 0.05 mU/ml stimulated lipolysis, protein kinase and cyclic AMP accumulation in isolated fat cells from fed and fasted rats. Changes in cyclic AMP levels and in the protein kinase activity ratio were well correlated temporally. The protein kinase activity ratio was potentiated by adenosine deaminase. A sudden increase or decrease in either ACTH or dibutyryl cyclic AMP concentration was associated with a rapid and corresponding change in the rate of glycerol production. With ACTH, the changes in glycerol production were accompanied by appropriate changes in cyclic AMP levels. Actinomycin-D (10 UM) did not affect lipolysis or cyclic AMP accumulation activated by ACTH in fat cells."}
{"id": "PMID:214473", "title": "Cyclic AMP-dependent regulation of ornithine decarboxylase activity in Chinese hamster ovary cells maintained with a salts/glucose medium.", "content": "Ornithine decarboxylase activity (ODC) increased about 7 fold 6--8 h following 10mM asparagine (ASN) addition to confluent cultures that had been previously serum deprived and then placed in a salts/glucose medium. Optimal concentrations of dibutyryl cAMP (dB cAMP) when incubated with the ASN caused up to a 50 fold increase in the activity of this enzyme after 7--8 h. The enhancement of ODC activity by ASN and dB cAMP was not sensitive to continuous (0--7 h) treatment with actinomycin D but similar treatment with cycloheximide depressed enzyme activity 40--60%. The synergistic stimulation of ODC activity by dB cAMP added with ASN was dose dependent and the dB cAMP stimulation of ODC activity displayed an absolute requirement for ASN when cells were maintained in the salts/glucose medium. The addition of dB cAMP always further enhanced ODC activity above the levels produced by addition of various levels of ASN (1 to 40mM) to the salts/glucose medium. Other agents which elevated cAMP levels such as 1-methyl-3-isobutylxanthine (IBMX) also enhanced ODC activity when administered with ASN. Additionally, treatment with sodium butyrate at concentrations ranging from 0.001mM to 5.0mM did not elevate ODC activity above the activity obtained with ASN alone. Addition of dB cAMP at various times after placing cells in salts/glucose medium with ASN further stimulated ODC activity only when added during the first 3-4 h. These results demonstrate the involvement of cAMP in the ASN mediated stimulation of ODC activity using cells maintained in a salts/glucose medium.", "contents": "Cyclic AMP-dependent regulation of ornithine decarboxylase activity in Chinese hamster ovary cells maintained with a salts/glucose medium. Ornithine decarboxylase activity (ODC) increased about 7 fold 6--8 h following 10mM asparagine (ASN) addition to confluent cultures that had been previously serum deprived and then placed in a salts/glucose medium. Optimal concentrations of dibutyryl cAMP (dB cAMP) when incubated with the ASN caused up to a 50 fold increase in the activity of this enzyme after 7--8 h. The enhancement of ODC activity by ASN and dB cAMP was not sensitive to continuous (0--7 h) treatment with actinomycin D but similar treatment with cycloheximide depressed enzyme activity 40--60%. The synergistic stimulation of ODC activity by dB cAMP added with ASN was dose dependent and the dB cAMP stimulation of ODC activity displayed an absolute requirement for ASN when cells were maintained in the salts/glucose medium. The addition of dB cAMP always further enhanced ODC activity above the levels produced by addition of various levels of ASN (1 to 40mM) to the salts/glucose medium. Other agents which elevated cAMP levels such as 1-methyl-3-isobutylxanthine (IBMX) also enhanced ODC activity when administered with ASN. Additionally, treatment with sodium butyrate at concentrations ranging from 0.001mM to 5.0mM did not elevate ODC activity above the activity obtained with ASN alone. Addition of dB cAMP at various times after placing cells in salts/glucose medium with ASN further stimulated ODC activity only when added during the first 3-4 h. These results demonstrate the involvement of cAMP in the ASN mediated stimulation of ODC activity using cells maintained in a salts/glucose medium."}
{"id": "PMID:214477", "title": "Inhibition of corrosion during autoclave sterilization of carbon steel dental instruments.", "content": "Comparisons were made of several dip-applied corrosion inhibitors for protection of carbon steel dental instruments during autoclaving. Although none were totally effective, several provided significant corrosion inhibition. Sodium nitrite and one proprietary inhibitor were about equally effective and notably superior to the other inhibitors investigated. Because sodium nitrite is a food preservative that is relatively harmless when ingested in small quantities, whereas commercial inhibitors are of proprietary composition and unspecified toxicity, we prefer to use sodium nitrite for corrosion inhibition during autoclaving. Sodium nitritie is readily available from chemical suppliers and is generally much less expensive than most commercial inhibitors. Although the autoclave used in this investigation is typical of many used in clinical situations, minor variations in design, steam impurities, and other unknown factors might effect the results. Further research is needed to determine the corrosive effects of impurities in the steam supply, residual detergents, method of postautoclave drying, steam supply deoxygenation, pH, and possibly the use of oxygen scavengers within the autoclave.", "contents": "Inhibition of corrosion during autoclave sterilization of carbon steel dental instruments. Comparisons were made of several dip-applied corrosion inhibitors for protection of carbon steel dental instruments during autoclaving. Although none were totally effective, several provided significant corrosion inhibition. Sodium nitrite and one proprietary inhibitor were about equally effective and notably superior to the other inhibitors investigated. Because sodium nitrite is a food preservative that is relatively harmless when ingested in small quantities, whereas commercial inhibitors are of proprietary composition and unspecified toxicity, we prefer to use sodium nitrite for corrosion inhibition during autoclaving. Sodium nitritie is readily available from chemical suppliers and is generally much less expensive than most commercial inhibitors. Although the autoclave used in this investigation is typical of many used in clinical situations, minor variations in design, steam impurities, and other unknown factors might effect the results. Further research is needed to determine the corrosive effects of impurities in the steam supply, residual detergents, method of postautoclave drying, steam supply deoxygenation, pH, and possibly the use of oxygen scavengers within the autoclave."}
{"id": "PMID:214475", "title": "Role of cGMP in isolated rat parotid acinar cells.", "content": "The role of cGMP as the intracellular mediator of the activation of cholinergic receptors in the secretory cells of the rat parotid gland was investigated in vitro using isolated rat parotid acinar cells. It was demonstrated that this cyclic nucleotide is involved in the intracellular translation of activation of muscarinic cholinergic receptors in these cells.", "contents": "Role of cGMP in isolated rat parotid acinar cells. The role of cGMP as the intracellular mediator of the activation of cholinergic receptors in the secretory cells of the rat parotid gland was investigated in vitro using isolated rat parotid acinar cells. It was demonstrated that this cyclic nucleotide is involved in the intracellular translation of activation of muscarinic cholinergic receptors in these cells."}
{"id": "PMID:214482", "title": "Tendon transfers for radial nerve palsy: use of superficialis tendons for digital extension.", "content": "Since 1959, 22 patients have had wrist extension restored by transfer of the pronator teres to the extensor carpi radialis longus and brevis, common finger extension by transfer of the superficialis of the long finger, independent thumb and index finger extension by transfer of the superficialis of the ring finger, and abduction of the thumb by transfer of the flexor carpi radialis at the wrist joint level. Twenty-one of 22 patients have been evaluated from 8 months to 15 years after operation, with an average follow-up of 4.5 years. By our new system of evaluation, there were 10 excellent results, six good results, five fair results, and all patients improved. Sixteen patients obtained full, independent thumb-index finger extension, three had fair function, and two obtained thumb-index extension by tenodesis of the transfer. This procedure allows full metacarpophalangeal extension independent of wrist position, provides thumb-index finger extension independent of the ulnar three digits, and maintains the dorsal-radial-to-volar-ulnar plane of functional motion of the wrist by retaining the flexor carpi ulnaris.", "contents": "Tendon transfers for radial nerve palsy: use of superficialis tendons for digital extension. Since 1959, 22 patients have had wrist extension restored by transfer of the pronator teres to the extensor carpi radialis longus and brevis, common finger extension by transfer of the superficialis of the long finger, independent thumb and index finger extension by transfer of the superficialis of the ring finger, and abduction of the thumb by transfer of the flexor carpi radialis at the wrist joint level. Twenty-one of 22 patients have been evaluated from 8 months to 15 years after operation, with an average follow-up of 4.5 years. By our new system of evaluation, there were 10 excellent results, six good results, five fair results, and all patients improved. Sixteen patients obtained full, independent thumb-index finger extension, three had fair function, and two obtained thumb-index extension by tenodesis of the transfer. This procedure allows full metacarpophalangeal extension independent of wrist position, provides thumb-index finger extension independent of the ulnar three digits, and maintains the dorsal-radial-to-volar-ulnar plane of functional motion of the wrist by retaining the flexor carpi ulnaris."}
{"id": "PMID:214493", "title": "Histochemical and cytochemical localization of (Na+-K+)-activated adenosine triphosphatase in the acini of dog submandibular glands.", "content": "p-Nitrophenyl phosphatase (p-NPPase) activity of (Na+-K+)-activated adenosine triphosphatase ((Na+-K+)-ATPase) on the acinar cells of dog submandibular gland was demonstrated by using light microscopy. The reaction products of p-NPPase of fresh frozen sections were seen to be localized on the basal parts of acini, and disappeared when the sections were incubated in medium containing 10(-3) Mouabain or in a K-free medium. Under the electron microscope, the reaction products of ATPase were found to be localized on the basolateral plasma membrane of both serous and mucous cells. On the microvilli of the luminal plasma membrane of the acinar cell, a small quantity of the reaction products was also present. This localization of ATPase reaction products on the serous and mucous cells seemed to coincide well with that of p-NPPase activity observed on the acini under light microscopy. Possible explanations are given regarding distribution of the above mentioned enzymes in relation to the cation transport of the plasma membrane. Structural and functional asymmetrical properties of acinar cells of the dog submandibular gland are also discussed.", "contents": "Histochemical and cytochemical localization of (Na+-K+)-activated adenosine triphosphatase in the acini of dog submandibular glands. p-Nitrophenyl phosphatase (p-NPPase) activity of (Na+-K+)-activated adenosine triphosphatase ((Na+-K+)-ATPase) on the acinar cells of dog submandibular gland was demonstrated by using light microscopy. The reaction products of p-NPPase of fresh frozen sections were seen to be localized on the basal parts of acini, and disappeared when the sections were incubated in medium containing 10(-3) Mouabain or in a K-free medium. Under the electron microscope, the reaction products of ATPase were found to be localized on the basolateral plasma membrane of both serous and mucous cells. On the microvilli of the luminal plasma membrane of the acinar cell, a small quantity of the reaction products was also present. This localization of ATPase reaction products on the serous and mucous cells seemed to coincide well with that of p-NPPase activity observed on the acini under light microscopy. Possible explanations are given regarding distribution of the above mentioned enzymes in relation to the cation transport of the plasma membrane. Structural and functional asymmetrical properties of acinar cells of the dog submandibular gland are also discussed."}
{"id": "PMID:214494", "title": "Preparation of crude Clostridium histolyticum collagenase for therapeutic purposes.", "content": "The production of a freeze-dried enzymatic preparation from the category of crude collagenases has been described. The method is based on the utilization of a highly proteolytic Clostridium histolyticum strain whose products have more advantageous properties for therapeutic purposes than the products of the strain commonly used as yet.", "contents": "Preparation of crude Clostridium histolyticum collagenase for therapeutic purposes. The production of a freeze-dried enzymatic preparation from the category of crude collagenases has been described. The method is based on the utilization of a highly proteolytic Clostridium histolyticum strain whose products have more advantageous properties for therapeutic purposes than the products of the strain commonly used as yet."}
{"id": "PMID:214495", "title": "A comparative study of functional activity and cytochemical characteristics of human and rabbit microphages.", "content": "Substantial differences were found in the cytochemical indices of human and rabbit microphages. Regular changes in the enzymic activity and the levels of some biopolymers were observed in the microphages in the process of phagocytosis. The extent and (in some cases) tendency of these changes in human and rabbit microphages are not the same. Cytochemical indices provide significant information on the functional activity of the microphage system within one species. At the interspecies level, such information proves to be inadequate for the characteristic of the phagocytic ability of microphages unless humoral non-specific means of protection are taken into account.", "contents": "A comparative study of functional activity and cytochemical characteristics of human and rabbit microphages. Substantial differences were found in the cytochemical indices of human and rabbit microphages. Regular changes in the enzymic activity and the levels of some biopolymers were observed in the microphages in the process of phagocytosis. The extent and (in some cases) tendency of these changes in human and rabbit microphages are not the same. Cytochemical indices provide significant information on the functional activity of the microphage system within one species. At the interspecies level, such information proves to be inadequate for the characteristic of the phagocytic ability of microphages unless humoral non-specific means of protection are taken into account."}
{"id": "PMID:214496", "title": "Characterization of a specific adenosine receptor on human lymphocytes.", "content": "We have examined the mechanism of action of adenosine, a naturally occurring nucleoside that has profound effects on lymphocyte function. Adenosine (0.01 micrometer to 10 micrometer) increased lymphocytes cAMP levels in a dose-dependent fashion with a maximal (10 micrometer) increase of about 4-fold, whereas adenine, guanosine, and inosine had no effect on lymphocyte cAMP levels at concentrations of 100 micrometer. Adenosine appears to act on the cell surface since 1) 2-chloroadenosine, a poorly metabolized adenosine analogue, was as active as adenosine and 2) dipyridamole, which markedly inhibited [3H]-adenosine uptake by human lymphocytes, did not affect adenosine-induced accumulation of cAMP. The specificity of the adenosine effect was established by showing that the methylxanthine derivatives, theophylline and 3-isobutyl-1-methylxanthine (IBMX), specifically block the accumulation of cAMP in lymphocytes induced by adenosine. Theophylline is a competitive inhibitor of the effect of adenosine, with an estimated dissociation constant of theophylline-receptor complex of about 6.3 X 10(-7) M. The results suggest that adenosine increases the intracellular cAMP content of lymphocytes as a result of its interaction with a specific membrane receptor which results in the activation of adenylate cyclase.", "contents": "Characterization of a specific adenosine receptor on human lymphocytes. We have examined the mechanism of action of adenosine, a naturally occurring nucleoside that has profound effects on lymphocyte function. Adenosine (0.01 micrometer to 10 micrometer) increased lymphocytes cAMP levels in a dose-dependent fashion with a maximal (10 micrometer) increase of about 4-fold, whereas adenine, guanosine, and inosine had no effect on lymphocyte cAMP levels at concentrations of 100 micrometer. Adenosine appears to act on the cell surface since 1) 2-chloroadenosine, a poorly metabolized adenosine analogue, was as active as adenosine and 2) dipyridamole, which markedly inhibited [3H]-adenosine uptake by human lymphocytes, did not affect adenosine-induced accumulation of cAMP. The specificity of the adenosine effect was established by showing that the methylxanthine derivatives, theophylline and 3-isobutyl-1-methylxanthine (IBMX), specifically block the accumulation of cAMP in lymphocytes induced by adenosine. Theophylline is a competitive inhibitor of the effect of adenosine, with an estimated dissociation constant of theophylline-receptor complex of about 6.3 X 10(-7) M. The results suggest that adenosine increases the intracellular cAMP content of lymphocytes as a result of its interaction with a specific membrane receptor which results in the activation of adenylate cyclase."}
{"id": "PMID:214497", "title": "Cell surface glycoproteins of rat lymphocytes. I. Correlation of mitogenic stimulation by periodate or neuraminidase and galactose oxidase with the presence of papain-sensitive glycoproteins.", "content": "Oxidation of viable rat lymph node lymphocytes with either periodate or a combination of neuraminidase and galactose oxidase (NGO), followed by reduction with tritiated sodium borohydride, labels similar sets of cell-surface molecules as assessed by sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis. Periodate and NGO induce blast transformation of lymph node lymphocytes (oxidative mitogenesis), and borohydride reduction inhibits the proliferative response. Thus, it is inferred that some or all of the glycoproteins that are labeled with tritiated borohydride may be involved in mediating the stimulation caused by the oxidizing agents. Treatment of lymph node lymphocytes with 5 units/ml papain abolishes the response to periodate or NGO but does not significantly affect the response to Con A. At the same time, papain treatment eliminates the labeled bands representing six high m.w. glycoproteins (175,000, 170,000, 160,000, 155,000, 100,000, and 70,000 daltons). No significant effect is seen on the labeling of the other components visualized in the slab gels. The results implicate the subset of six high m.w. papain-sensitive sialoglycoproteins in mediating oxidative mitogenesis of rat lymph node lymphocytes.", "contents": "Cell surface glycoproteins of rat lymphocytes. I. Correlation of mitogenic stimulation by periodate or neuraminidase and galactose oxidase with the presence of papain-sensitive glycoproteins. Oxidation of viable rat lymph node lymphocytes with either periodate or a combination of neuraminidase and galactose oxidase (NGO), followed by reduction with tritiated sodium borohydride, labels similar sets of cell-surface molecules as assessed by sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis. Periodate and NGO induce blast transformation of lymph node lymphocytes (oxidative mitogenesis), and borohydride reduction inhibits the proliferative response. Thus, it is inferred that some or all of the glycoproteins that are labeled with tritiated borohydride may be involved in mediating the stimulation caused by the oxidizing agents. Treatment of lymph node lymphocytes with 5 units/ml papain abolishes the response to periodate or NGO but does not significantly affect the response to Con A. At the same time, papain treatment eliminates the labeled bands representing six high m.w. glycoproteins (175,000, 170,000, 160,000, 155,000, 100,000, and 70,000 daltons). No significant effect is seen on the labeling of the other components visualized in the slab gels. The results implicate the subset of six high m.w. papain-sensitive sialoglycoproteins in mediating oxidative mitogenesis of rat lymph node lymphocytes."}
{"id": "PMID:214499", "title": "Role of the murine major histocompatibility complex in macrophage-mediated cytolysis.", "content": "Peritoneal cells from congeneic resistant mice infected with BCG displayed differential cytotoxicity toward tumor cells destroying more allogeneic tumor cells than syngeneic tumor cells. This observation was made regardless of the tumor cells used or the effector cell source. The responsible effector cell remained in a doubly adherent population, was sensitive to carrageenan and silica, insensitive to anti-thymocyte sera, and is probably a macrophage. Activated macrophages were capable of reacting against tumor cells as well as histoincompatible embryonic cells. These observations may indicate that macrophages are capable of discriminating cell surface components linked to the major histocompatibility complex.", "contents": "Role of the murine major histocompatibility complex in macrophage-mediated cytolysis. Peritoneal cells from congeneic resistant mice infected with BCG displayed differential cytotoxicity toward tumor cells destroying more allogeneic tumor cells than syngeneic tumor cells. This observation was made regardless of the tumor cells used or the effector cell source. The responsible effector cell remained in a doubly adherent population, was sensitive to carrageenan and silica, insensitive to anti-thymocyte sera, and is probably a macrophage. Activated macrophages were capable of reacting against tumor cells as well as histoincompatible embryonic cells. These observations may indicate that macrophages are capable of discriminating cell surface components linked to the major histocompatibility complex."}
{"id": "PMID:214504", "title": "Comparative toxicity of polychlorinated biphenyl and polybrominated biphenyl in the rat liver: light and electron microscopic alterations after subacute dietary exposure.", "content": "The comparative toxicity of polychlorinated biphenyl (PCB) and polybrominated biphenyl (PBB) in livers was studied in male Holtzman rats. Four-week-old animals were fed at dietary levels of 0, 5, 50, or 500 ppm for 5 weeks and then sacrificed. The mean liver-body weight ratios of the 50 and 500 ppm groups were increased. Histopathologic examination of the livers revealed fatty degenerative change associated with both compounds. This change was more marked at 500 than at 50 ppm. Various sized lamellar cytoplasmic inclusions were detected in livers of animals fed 500 ppm of either compound. However, the inclusions were more numerous in the PBB-treated rats. Several animals fed 50 ppm PBB had a few inclusions. In rats that received 500 ppm PBB, hypertrophic degenerative hepatocytes were present around the central veins. On the periphery of this change there were occasionally multinucleated hepatocytes. Electron microscopic examination at a dose level of 5 ppm in both the PCB and PBB groups showed a slight proliferation of smooth endoplasmic reticulum (SER), a moderate increase of lipid droplets and some liposomes, and a marked proliferation of Golgi condensing vesicles containing lipoprotein particles. A decreased number of mitochondria and lysosomes was also observed. At 50 ppm, similar but more marked ultrastructural alterations were seen. In addition, an increased number of branched and cup-shaped profiles of mitochondria and a decreased number of Golgi condensing vesicles containing lipoprotein particles were observed. Concentric membranous cytoplasmic whorls were encountered only in the 50 ppm PBB-treated rats. At 500 ppm the number of mitochondria decreased in both groups. There was also a marked increase in the number of SER and liposomes concomitant with a decreased number of Golgi condensing vesicles containing lipoprotein granules. Membranous whorls were also present in the 500 ppm groups.", "contents": "Comparative toxicity of polychlorinated biphenyl and polybrominated biphenyl in the rat liver: light and electron microscopic alterations after subacute dietary exposure. The comparative toxicity of polychlorinated biphenyl (PCB) and polybrominated biphenyl (PBB) in livers was studied in male Holtzman rats. Four-week-old animals were fed at dietary levels of 0, 5, 50, or 500 ppm for 5 weeks and then sacrificed. The mean liver-body weight ratios of the 50 and 500 ppm groups were increased. Histopathologic examination of the livers revealed fatty degenerative change associated with both compounds. This change was more marked at 500 than at 50 ppm. Various sized lamellar cytoplasmic inclusions were detected in livers of animals fed 500 ppm of either compound. However, the inclusions were more numerous in the PBB-treated rats. Several animals fed 50 ppm PBB had a few inclusions. In rats that received 500 ppm PBB, hypertrophic degenerative hepatocytes were present around the central veins. On the periphery of this change there were occasionally multinucleated hepatocytes. Electron microscopic examination at a dose level of 5 ppm in both the PCB and PBB groups showed a slight proliferation of smooth endoplasmic reticulum (SER), a moderate increase of lipid droplets and some liposomes, and a marked proliferation of Golgi condensing vesicles containing lipoprotein particles. A decreased number of mitochondria and lysosomes was also observed. At 50 ppm, similar but more marked ultrastructural alterations were seen. In addition, an increased number of branched and cup-shaped profiles of mitochondria and a decreased number of Golgi condensing vesicles containing lipoprotein particles were observed. Concentric membranous cytoplasmic whorls were encountered only in the 50 ppm PBB-treated rats. At 500 ppm the number of mitochondria decreased in both groups. There was also a marked increase in the number of SER and liposomes concomitant with a decreased number of Golgi condensing vesicles containing lipoprotein granules. Membranous whorls were also present in the 500 ppm groups."}
{"id": "PMID:214507", "title": "T-cell lymphoma induction by radiation leukemia virus in athymic nude mice.", "content": "We report the development of extrathymic lymphoblastic lymphomas in RadLV-inoculated congenitally athymic nude mice. Thus, a leukemogenic virus which appears to require the presence of a thymus for its replication in normothymic mice can infect and transform target cells in the absence of this organ in the athymic host. The cells of one of these lymphomas have been established in vitro as a permanent cell line, BALB/Nu1. This cell line as well as a lymphoma induced in NIH/Swiss nude mice exhibit several T-cell markers, including terminal deoxynucleotidyl transferase activity, Thy-1.2, and Ly-2.2, but not Ly-1.2 nor TL. Ig determinants were not detected. The characteristics of the tumor cells support the view that cells with T-cell markers may normally exist in nude mice and undergo neoplastic transformation and clonal expansion after infection with a leukemogenic virus. The alternative possibility that virus-induced differentiation of prothymocytes may lead to the expression of Thy-1.2 and Ly-2.2 antigens is also considered. BALB/Nu1 cells release large numbers of type C viral particles. The virus, designated radiation leukemia virus (RadLV)/Nu1, has RTase activity and the protein profile characteristic of murine leukemia virus (MuLV). In radioimmunoassays, it cross-reacts completely with RadLV/VL3, a virus obtained from RadLV-induced C57BL/Ka thymic lymphoma cells in culture, and slightly with a xenotropic virus (BALB:virus-2) and with AKR MuLV. On inoculation into C57BL/Ka mice it has thymotropic and leukemogenic activity. In vitro it is B-tropic, poorly fibrotropic, and has limited xenotropic activity. Thus, RadLV/Nu1 appears to be biologically and serologically similar or identical to its parent virus, RadLV.", "contents": "T-cell lymphoma induction by radiation leukemia virus in athymic nude mice. We report the development of extrathymic lymphoblastic lymphomas in RadLV-inoculated congenitally athymic nude mice. Thus, a leukemogenic virus which appears to require the presence of a thymus for its replication in normothymic mice can infect and transform target cells in the absence of this organ in the athymic host. The cells of one of these lymphomas have been established in vitro as a permanent cell line, BALB/Nu1. This cell line as well as a lymphoma induced in NIH/Swiss nude mice exhibit several T-cell markers, including terminal deoxynucleotidyl transferase activity, Thy-1.2, and Ly-2.2, but not Ly-1.2 nor TL. Ig determinants were not detected. The characteristics of the tumor cells support the view that cells with T-cell markers may normally exist in nude mice and undergo neoplastic transformation and clonal expansion after infection with a leukemogenic virus. The alternative possibility that virus-induced differentiation of prothymocytes may lead to the expression of Thy-1.2 and Ly-2.2 antigens is also considered. BALB/Nu1 cells release large numbers of type C viral particles. The virus, designated radiation leukemia virus (RadLV)/Nu1, has RTase activity and the protein profile characteristic of murine leukemia virus (MuLV). In radioimmunoassays, it cross-reacts completely with RadLV/VL3, a virus obtained from RadLV-induced C57BL/Ka thymic lymphoma cells in culture, and slightly with a xenotropic virus (BALB:virus-2) and with AKR MuLV. On inoculation into C57BL/Ka mice it has thymotropic and leukemogenic activity. In vitro it is B-tropic, poorly fibrotropic, and has limited xenotropic activity. Thus, RadLV/Nu1 appears to be biologically and serologically similar or identical to its parent virus, RadLV."}
{"id": "PMID:214505", "title": "Comparative toxicity of polychlorinated biphenyl and polybrominated biphenylin the rat thyroid gland: light and electron microscopic alterations after subacute dietary exposure.", "content": "The comparative toxicity of polychlorinated biphenyl (PCB) and polybrominated biphenyl (PBB) in thyroid glands was studied in male Holtzman rats. Four-week-old animals were fed at dietary levels of 0, 5, 50, and 500 ppm for 5 weeks and then sacrificed. PCB and PBB produced similar dose-dependent ultrastructural lesions in thyroid follicular cells of rats. The daily administration of 5 ppm of either PCB or PBB resulted in the accumulation of large membrane-limited colloid droplets and electron-dense lysosomal bodies within the cytoplasm of follicular cells. Microvilli were short and abnormally branched, and unique cytoplasmic processes extended from the apical surface of follicular cells into the luminal colloid. Similar but more severe ultrastructural changes were observed in thyroid glands of rats administered 50 and 500 ppm of either PCB or PBB. Many follicular cells were distended with large abnormal lysosomal bodies and colloid droplets. Mitochondria were often vacuolated with disrupted cristae. Microvilli were blunt with abnormal branching or absent from areas of the luminal surface of follicular cells. Processes of apical cytoplasm often extended into the follicular lumen in areas devoid of microvilli. Follicular cells remained responsive after the feeding of either PCB or PBB and underwent moderate compensatory hypertrophy and hyperplasia. Thyroid follicles were smaller than in controls and were lined by more columnar cells that occasionally formed papillary projections into the follicular lumens. PCB and PBB produced similar ultrastructural lesions in thyroid follicular cells which appeared to interfere with the synthesis and secretion of thyroxine.", "contents": "Comparative toxicity of polychlorinated biphenyl and polybrominated biphenylin the rat thyroid gland: light and electron microscopic alterations after subacute dietary exposure. The comparative toxicity of polychlorinated biphenyl (PCB) and polybrominated biphenyl (PBB) in thyroid glands was studied in male Holtzman rats. Four-week-old animals were fed at dietary levels of 0, 5, 50, and 500 ppm for 5 weeks and then sacrificed. PCB and PBB produced similar dose-dependent ultrastructural lesions in thyroid follicular cells of rats. The daily administration of 5 ppm of either PCB or PBB resulted in the accumulation of large membrane-limited colloid droplets and electron-dense lysosomal bodies within the cytoplasm of follicular cells. Microvilli were short and abnormally branched, and unique cytoplasmic processes extended from the apical surface of follicular cells into the luminal colloid. Similar but more severe ultrastructural changes were observed in thyroid glands of rats administered 50 and 500 ppm of either PCB or PBB. Many follicular cells were distended with large abnormal lysosomal bodies and colloid droplets. Mitochondria were often vacuolated with disrupted cristae. Microvilli were blunt with abnormal branching or absent from areas of the luminal surface of follicular cells. Processes of apical cytoplasm often extended into the follicular lumen in areas devoid of microvilli. Follicular cells remained responsive after the feeding of either PCB or PBB and underwent moderate compensatory hypertrophy and hyperplasia. Thyroid follicles were smaller than in controls and were lined by more columnar cells that occasionally formed papillary projections into the follicular lumens. PCB and PBB produced similar ultrastructural lesions in thyroid follicular cells which appeared to interfere with the synthesis and secretion of thyroxine."}
{"id": "PMID:214508", "title": "Recessive dystrophic epidermolysis bullosa. Evidence for increased collagenase as a genetic characteristic in cell culture.", "content": "Fibroblast cultures from patients with recessive dystrophic epidermolysis bullosa (RDEB) demonstrated an increased capacity to synthesize and secrete collagenase. This phenotypic trait appeared to distinguish RDEB from other genetically distinct forms of epidermolysis bullosa. The finding of increased collagenase may be a specific manifestation of these cells in that prototypic lysosomal and cytoplasmic enzymes were present in approximately normal concentrations. In addition, this trait persisted through many cell passages, suggesting that the property was genetically determined. The elevated concentrations of immunoreactive collagenase in fibroblast cultures of patients with RDEB reflected those previously observed in vivo (4) and support the concept of a pathogenetic role for the enzyme in the blistering phenomenon. In three of the cell lines, the increase in enzyme protein occurred in association with a structurally defective enzyme. The data suggest that this may be a characteristic of all RDEB cells.", "contents": "Recessive dystrophic epidermolysis bullosa. Evidence for increased collagenase as a genetic characteristic in cell culture. Fibroblast cultures from patients with recessive dystrophic epidermolysis bullosa (RDEB) demonstrated an increased capacity to synthesize and secrete collagenase. This phenotypic trait appeared to distinguish RDEB from other genetically distinct forms of epidermolysis bullosa. The finding of increased collagenase may be a specific manifestation of these cells in that prototypic lysosomal and cytoplasmic enzymes were present in approximately normal concentrations. In addition, this trait persisted through many cell passages, suggesting that the property was genetically determined. The elevated concentrations of immunoreactive collagenase in fibroblast cultures of patients with RDEB reflected those previously observed in vivo (4) and support the concept of a pathogenetic role for the enzyme in the blistering phenomenon. In three of the cell lines, the increase in enzyme protein occurred in association with a structurally defective enzyme. The data suggest that this may be a characteristic of all RDEB cells."}
{"id": "PMID:214506", "title": "In vitro assay for tumor promoters and anti-promoters.", "content": "Tumor promoters and anti-promoters have been shown to modify the induction of ornithine decarboxylase, the production of plasminogen activator, and the recovery of induced mutations. Data were presented to show that the recovery of mutagen-induced ouabain-resistant mutations in cultured Chinese hamster cells is increased with a tumor-promoter treatment and reduced by anti-promoter treatments. The results suggest that many induced mutations can either be repressed or derepressed by promoters or anti-promoters. The results also support the hypothesis that tumor initiation is due to a mutagenic event, while tumor promotion is the result of an epigenetic process involving cyclic nucleotide modulation of gene expression.", "contents": "In vitro assay for tumor promoters and anti-promoters. Tumor promoters and anti-promoters have been shown to modify the induction of ornithine decarboxylase, the production of plasminogen activator, and the recovery of induced mutations. Data were presented to show that the recovery of mutagen-induced ouabain-resistant mutations in cultured Chinese hamster cells is increased with a tumor-promoter treatment and reduced by anti-promoter treatments. The results suggest that many induced mutations can either be repressed or derepressed by promoters or anti-promoters. The results also support the hypothesis that tumor initiation is due to a mutagenic event, while tumor promotion is the result of an epigenetic process involving cyclic nucleotide modulation of gene expression."}
{"id": "PMID:214509", "title": "Preparation of functional smooth muscle cells from the rabbit aorta.", "content": "A procedure for dissociating the rabbit aorta into single, functional smooth muscle cells is described. After removal of adventitia and intima, slices of media were incubated with purified collagenase, elastase, and soybean trypsin inhibitor in a Krebs-Ringer buffer modified with Hepes, amino acids, and a [Ca2+] of 0.2 mM. After enzymatic digestion and mechanical shear, the yield of dispersed cells was approximately 25% based on DNA recovered. Greater than 95% of the cells excluded trypan blue and approximately 80-90% adhered to tissue culture dishes. By phase contrast microscopy, most of the cells were elongate and approximately 10 micron X 30 micron in size. The remainder were either spherical or highly crenated and contracted. Electron microscopy of the cells showed that immediately after dissociation greater than 95% could be identified as smooth muscle, though most had undergone some degree of structural change compared to cells in situ. Depending on the preparation, from 5 to 50% of these cells contracted in response to agonists. Cells shortened by 10-15% and developed numerous evaginations when stimulated by angiotensin II norepinephrine, or carbamylcholine. Cells relaxed after washout of agonists and could subsequently be restimulated. Specific inhibitors of each of the agonists blocked the contractile response. Dispersed cells cultured for 1-5 days contracted in even higher numbers than the freshly prepared cells, suggesting restoration of hormone binding and/or contractile function in culture. This preparation provides a system in which the physiology of individual vascular smooth muscle cells may be studied.", "contents": "Preparation of functional smooth muscle cells from the rabbit aorta. A procedure for dissociating the rabbit aorta into single, functional smooth muscle cells is described. After removal of adventitia and intima, slices of media were incubated with purified collagenase, elastase, and soybean trypsin inhibitor in a Krebs-Ringer buffer modified with Hepes, amino acids, and a [Ca2+] of 0.2 mM. After enzymatic digestion and mechanical shear, the yield of dispersed cells was approximately 25% based on DNA recovered. Greater than 95% of the cells excluded trypan blue and approximately 80-90% adhered to tissue culture dishes. By phase contrast microscopy, most of the cells were elongate and approximately 10 micron X 30 micron in size. The remainder were either spherical or highly crenated and contracted. Electron microscopy of the cells showed that immediately after dissociation greater than 95% could be identified as smooth muscle, though most had undergone some degree of structural change compared to cells in situ. Depending on the preparation, from 5 to 50% of these cells contracted in response to agonists. Cells shortened by 10-15% and developed numerous evaginations when stimulated by angiotensin II norepinephrine, or carbamylcholine. Cells relaxed after washout of agonists and could subsequently be restimulated. Specific inhibitors of each of the agonists blocked the contractile response. Dispersed cells cultured for 1-5 days contracted in even higher numbers than the freshly prepared cells, suggesting restoration of hormone binding and/or contractile function in culture. This preparation provides a system in which the physiology of individual vascular smooth muscle cells may be studied."}
{"id": "PMID:214510", "title": "The biologic significance of alloreactivity. The ontogeny of T-cell sets specific for alloantigens or modified self antigens.", "content": "We have analyzed the cellular basis of T-cell reactivity against lymphocytes expressing major histocompatibility complex (MHC) products that are foreign by virtue of polymorphism (alloantigens) or because of modification by chemicals or viruses. We find that early in ontogeny, prekiller activity against both trinitrophenyl (TNP)-coupled autologous MHC products and allogeneic MHC products resides in the same (Ly123(+)) T-cell pool; later in ontogeny alloreactivity is invested in Ly23 cells which, when activated, lyse TNP-coupled autologous cells as well as appropriate allogeneic target cells. We demonstrate that stimulation of Ly123(+) T cells in vitro by autologous cells coated with chemically-inactivated Sendai virus results in the formation of Ly23(+) cytolytic T lymphocytes (CTL) that specifically lyse both virus modified autologous target cells and unmodified allogeneic target cells. These results suggest the following model to account for the presence of large numbers of alloreactive T-cell clones in adult animals: continuous stimulation of Ly123 cells by autologous MHC antigens associated with foreign materials such as a virus results in the formation of Ly23 memory progeny carrying receptors that recognize MHC products that are foreign due to genetic polymorphism (alloantigens). In general, these studies indicate that alloaggression (as manifest by Ly23 cells in the CTL response) reflects a high degree of cross stimulation between physiologically relevant antigens, e.g., viral determinants associated with self MHC products, and biologically irrelevant allelic variants of the MHC.", "contents": "The biologic significance of alloreactivity. The ontogeny of T-cell sets specific for alloantigens or modified self antigens. We have analyzed the cellular basis of T-cell reactivity against lymphocytes expressing major histocompatibility complex (MHC) products that are foreign by virtue of polymorphism (alloantigens) or because of modification by chemicals or viruses. We find that early in ontogeny, prekiller activity against both trinitrophenyl (TNP)-coupled autologous MHC products and allogeneic MHC products resides in the same (Ly123(+)) T-cell pool; later in ontogeny alloreactivity is invested in Ly23 cells which, when activated, lyse TNP-coupled autologous cells as well as appropriate allogeneic target cells. We demonstrate that stimulation of Ly123(+) T cells in vitro by autologous cells coated with chemically-inactivated Sendai virus results in the formation of Ly23(+) cytolytic T lymphocytes (CTL) that specifically lyse both virus modified autologous target cells and unmodified allogeneic target cells. These results suggest the following model to account for the presence of large numbers of alloreactive T-cell clones in adult animals: continuous stimulation of Ly123 cells by autologous MHC antigens associated with foreign materials such as a virus results in the formation of Ly23 memory progeny carrying receptors that recognize MHC products that are foreign due to genetic polymorphism (alloantigens). In general, these studies indicate that alloaggression (as manifest by Ly23 cells in the CTL response) reflects a high degree of cross stimulation between physiologically relevant antigens, e.g., viral determinants associated with self MHC products, and biologically irrelevant allelic variants of the MHC."}
{"id": "PMID:214511", "title": "In vitro effects of Epstein-Barr virus on peripheral blood mononuclear cells from patients with rheumatoid arthritis and normal subjects.", "content": "Peripheral blood mononuclear cells from 10 patients with rheumatoid arthritis and 9 control subjects were cultured in vitro for 30 days with and without infection by Epstein-Barr virus. All cultures showed polyclonal stimulation of B cells as indicated by rising levels of IgM in the culture supernates, reaching maximal at 18-24 days, and with no quantitative or kinetic difference between the RA and control cells. IgM anti-IgG was also produced in both groups and maximally at 18-24 days, but in greater quantity by the RA lymphocytes. The anti-IgG made by the RA lymphocytes was more easily absorbed by solid phase IgG than was the anti-IgG made by the normal lymphocytes and thus was judged to be of higher affinity. RA lymphocytes uninfected with EBV had higher transformation scores than did the normal controls and developed spontaneously into permanent cell lines in six instances.", "contents": "In vitro effects of Epstein-Barr virus on peripheral blood mononuclear cells from patients with rheumatoid arthritis and normal subjects. Peripheral blood mononuclear cells from 10 patients with rheumatoid arthritis and 9 control subjects were cultured in vitro for 30 days with and without infection by Epstein-Barr virus. All cultures showed polyclonal stimulation of B cells as indicated by rising levels of IgM in the culture supernates, reaching maximal at 18-24 days, and with no quantitative or kinetic difference between the RA and control cells. IgM anti-IgG was also produced in both groups and maximally at 18-24 days, but in greater quantity by the RA lymphocytes. The anti-IgG made by the RA lymphocytes was more easily absorbed by solid phase IgG than was the anti-IgG made by the normal lymphocytes and thus was judged to be of higher affinity. RA lymphocytes uninfected with EBV had higher transformation scores than did the normal controls and developed spontaneously into permanent cell lines in six instances."}
{"id": "PMID:214512", "title": "The induction of virus-specific cytotoxic T lymphocytes with solubilized viral and membrane proteins.", "content": "Reconstituted membranes were prepared from detergent solubilized P815 (H-2d) tumor cell membranes and solubilized Sendai virus protein. These reconstituted membranes stimulated a virus-specific H-2-restricted secondary CTL response. Stimulating activity was dependent upon the presence of both viral and P815 protein in the same membrane and was restricted to the H-2 specificity present in the reconstituted membrane. Liposomes prepared from solubilized Sendai virus proteins and partially purified H-2 alloantigen also had activity for CTL induction. The results demonstrate the feasibility of using detergent solubilized membrane proteins to study antigen recognition by virus-specific, H-2 restricted cytolytic T lymphocytes.", "contents": "The induction of virus-specific cytotoxic T lymphocytes with solubilized viral and membrane proteins. Reconstituted membranes were prepared from detergent solubilized P815 (H-2d) tumor cell membranes and solubilized Sendai virus protein. These reconstituted membranes stimulated a virus-specific H-2-restricted secondary CTL response. Stimulating activity was dependent upon the presence of both viral and P815 protein in the same membrane and was restricted to the H-2 specificity present in the reconstituted membrane. Liposomes prepared from solubilized Sendai virus proteins and partially purified H-2 alloantigen also had activity for CTL induction. The results demonstrate the feasibility of using detergent solubilized membrane proteins to study antigen recognition by virus-specific, H-2 restricted cytolytic T lymphocytes."}
{"id": "PMID:214513", "title": "Specific adsorption of H-2-restricted cytotoxi T cells to macrophage monolayers.", "content": "These experiments tested whether Tc cells specific for foreign antigen (X) plus self H-2 adsorbed to macrophage monolayers displaying (a) X with allogeneic H-2; (B) self H-2 alone; (c) X plus self H-2. Specific adsorption occurred only in case (c), a result compatible with altered self and requiring further operational assumptions in dual recognition models.", "contents": "Specific adsorption of H-2-restricted cytotoxi T cells to macrophage monolayers. These experiments tested whether Tc cells specific for foreign antigen (X) plus self H-2 adsorbed to macrophage monolayers displaying (a) X with allogeneic H-2; (B) self H-2 alone; (c) X plus self H-2. Specific adsorption occurred only in case (c), a result compatible with altered self and requiring further operational assumptions in dual recognition models."}
{"id": "PMID:214517", "title": "Genomic RNA of the murine coronavirus JHM.", "content": "Genomic RNA extracted from the purified murine coronavirus JHM sediments between 52S and 54S in aqueous sucrose gradients. The RNA is single-stranded and has an apparent mol. wt. of 5.4 to 6.5 X 10(6), as determined by electrophoresis in polyacrylamide agarose gels of different concentrations. The presence of polyadenylate sequences in the RNA is demonstrated by binding to oligo-)dT) cellulose and digestion with ribonucleases A and T1. The purified RNA does not dissociate into subunits at high temperatures or in high concentrations of DMSO and is infectious.", "contents": "Genomic RNA of the murine coronavirus JHM. Genomic RNA extracted from the purified murine coronavirus JHM sediments between 52S and 54S in aqueous sucrose gradients. The RNA is single-stranded and has an apparent mol. wt. of 5.4 to 6.5 X 10(6), as determined by electrophoresis in polyacrylamide agarose gels of different concentrations. The presence of polyadenylate sequences in the RNA is demonstrated by binding to oligo-)dT) cellulose and digestion with ribonucleases A and T1. The purified RNA does not dissociate into subunits at high temperatures or in high concentrations of DMSO and is infectious."}
{"id": "PMID:214518", "title": "Early events in the interaction between foot-and mouth disease virus and primary pig kidney cells.", "content": "Foot-and-mouth disease virus (FMDV) attached to pig kidney cells at 0 degrees C and could only be recovered in a form with a sedimentation coefficient and buoyant density lower than that of the native virus. Incubation of the virus-cell complex at 37 degrees C caused disruption of about 80% of the particles into a 12S protein sub-unit that had the same polypeptide composition as that produced by reducing the pH of the virus below pH7. The remaining 20% had the same polypeptide and RNA composition as the native virus but it had a lower sedimentation coefficient, buoyant density and specific infectivity. These lower values are probably due to the association of the virus with cell membrane components. The 12S subunits were shown to be located inside the cell, indicating that disruption of the virus had occurred within the cell. The results are discussed in relation to the different cell mediated alteration of other picornaviruses.", "contents": "Early events in the interaction between foot-and mouth disease virus and primary pig kidney cells. Foot-and-mouth disease virus (FMDV) attached to pig kidney cells at 0 degrees C and could only be recovered in a form with a sedimentation coefficient and buoyant density lower than that of the native virus. Incubation of the virus-cell complex at 37 degrees C caused disruption of about 80% of the particles into a 12S protein sub-unit that had the same polypeptide composition as that produced by reducing the pH of the virus below pH7. The remaining 20% had the same polypeptide and RNA composition as the native virus but it had a lower sedimentation coefficient, buoyant density and specific infectivity. These lower values are probably due to the association of the virus with cell membrane components. The 12S subunits were shown to be located inside the cell, indicating that disruption of the virus had occurred within the cell. The results are discussed in relation to the different cell mediated alteration of other picornaviruses."}
{"id": "PMID:214519", "title": "Mastomys natalensis papilloma virus (MnPV), the causative agent of epithelial proliferations: characterization of the virus particle.", "content": "A virus (MnPV) with the structural characteristics of papilloma viruses was isolated from benign and malignant proliferations of adult animals of the inbred line 'GRA Giessen' of Mastomys natalensis. The particles can be banded in CsCl gradients at densities of 1.34 g/ml (full particles) and 1.29 g/ml (empty particles). The virus DNA has a buoyant density of 1.7104 g/ml and can exist in three different conformations (supercoiled circular, nicked circular and linear), the sedimentation values of which have been determined as 23 to 24S, 16 to 17S and 14 to 15S, respectively. Although the mol. wt. of MnPV DNA is similar to that of HPV 1 DNA, the size of the fragments obtained after cleavage of MnPV DNA with the restriction endonuclease Hae III is quite different from the pattern seen with human papilloma virus. The virion contains 12 different polypeptides; the major structural protein has a mol. wt. of 56 000. MnPV is shown to be the causative agent of the skin proliferations, because tumours can be induced by inoculation of purified virus, whereas no cutaneous alterations are observed when the particles are inoculated in the presence of anti-MnPV serum. MnPV can be re-isolated from the experimentally induced tumours.", "contents": "Mastomys natalensis papilloma virus (MnPV), the causative agent of epithelial proliferations: characterization of the virus particle. A virus (MnPV) with the structural characteristics of papilloma viruses was isolated from benign and malignant proliferations of adult animals of the inbred line 'GRA Giessen' of Mastomys natalensis. The particles can be banded in CsCl gradients at densities of 1.34 g/ml (full particles) and 1.29 g/ml (empty particles). The virus DNA has a buoyant density of 1.7104 g/ml and can exist in three different conformations (supercoiled circular, nicked circular and linear), the sedimentation values of which have been determined as 23 to 24S, 16 to 17S and 14 to 15S, respectively. Although the mol. wt. of MnPV DNA is similar to that of HPV 1 DNA, the size of the fragments obtained after cleavage of MnPV DNA with the restriction endonuclease Hae III is quite different from the pattern seen with human papilloma virus. The virion contains 12 different polypeptides; the major structural protein has a mol. wt. of 56 000. MnPV is shown to be the causative agent of the skin proliferations, because tumours can be induced by inoculation of purified virus, whereas no cutaneous alterations are observed when the particles are inoculated in the presence of anti-MnPV serum. MnPV can be re-isolated from the experimentally induced tumours."}
{"id": "PMID:214520", "title": "Efficient transfer of interferon-induced virus resistance between human cells.", "content": "The rate of development of interferon-induced virus resistance in a mixture of two human cell types (U and WISH) is determined by the cell type (WISH) in the mixture which responds first. This phenomenon has been shown with two types of interferon assay procedure, and with both vesicular stomatitis virus and Sindbis virus. The transfer of virus resistance from one human cell (WISH) to another (U) (homospecific transfer) is much more efficient than the transfer from mouse L cells to WISH cells (heterospecific transfer), as shown by a much lower ratio of donor to recipient cells required for maximum transfer as well as a more rapid transfer. Thus, virus protection afforded by the interferon system is amplified more efficiently in mixtures of different human cells than in mixtures of mouse and human cells. These results suggest that, in a mixed population of cells such as occurs in vivo, more slowly responding cells might be influenced by cells which respond more rapidly to interferon. A defensive role is suggested for this mechanism which amplifies protection due to interferon.", "contents": "Efficient transfer of interferon-induced virus resistance between human cells. The rate of development of interferon-induced virus resistance in a mixture of two human cell types (U and WISH) is determined by the cell type (WISH) in the mixture which responds first. This phenomenon has been shown with two types of interferon assay procedure, and with both vesicular stomatitis virus and Sindbis virus. The transfer of virus resistance from one human cell (WISH) to another (U) (homospecific transfer) is much more efficient than the transfer from mouse L cells to WISH cells (heterospecific transfer), as shown by a much lower ratio of donor to recipient cells required for maximum transfer as well as a more rapid transfer. Thus, virus protection afforded by the interferon system is amplified more efficiently in mixtures of different human cells than in mixtures of mouse and human cells. These results suggest that, in a mixed population of cells such as occurs in vivo, more slowly responding cells might be influenced by cells which respond more rapidly to interferon. A defensive role is suggested for this mechanism which amplifies protection due to interferon."}
{"id": "PMID:214521", "title": "Virus mutation during 'slow infection': temporal development and characterization of mutants of visna virus recovered from sheep.", "content": "Visna virus could be recovered from peripheral blood leukocytes of sheep for years after intracerebral inoculation. Viruses recovered from sheep prior to and several months after development of antibody were antigenically identical to the parental strain used for inoculation. Subsequently, mutant viruses which were not neutralized by the animals' sera were obtained. Longitudinal studies of leukocyte viruses collected from two infected sheep showed that more than one strain of virus could co-exist in the animal. Virus neutralization tests using sequentially collected sera and the viruses recovered from leukocytes revealed a sequential development of antibody to parental and then to each strain of mutant virus. Characterization of two of the mutant viruses showed that they were antigenically stable, virulent in cell culture and when inoculated into new sheep, elicited antibodies which cross reacted with the parental virus from which they were derived. This continuous mutation of Visna virus in persistently infected sheep may be a mechanism for the production of chronic disease.", "contents": "Virus mutation during 'slow infection': temporal development and characterization of mutants of visna virus recovered from sheep. Visna virus could be recovered from peripheral blood leukocytes of sheep for years after intracerebral inoculation. Viruses recovered from sheep prior to and several months after development of antibody were antigenically identical to the parental strain used for inoculation. Subsequently, mutant viruses which were not neutralized by the animals' sera were obtained. Longitudinal studies of leukocyte viruses collected from two infected sheep showed that more than one strain of virus could co-exist in the animal. Virus neutralization tests using sequentially collected sera and the viruses recovered from leukocytes revealed a sequential development of antibody to parental and then to each strain of mutant virus. Characterization of two of the mutant viruses showed that they were antigenically stable, virulent in cell culture and when inoculated into new sheep, elicited antibodies which cross reacted with the parental virus from which they were derived. This continuous mutation of Visna virus in persistently infected sheep may be a mechanism for the production of chronic disease."}
{"id": "PMID:214522", "title": "A re-appraisal of the biochemical map of foot-and-mouth disease virus RNA.", "content": "The proteins induced by infection of BHK 21 cells with foot-and-mouth disease virus have been compared by tryptic peptide analysis. The results indicate that there are three primary products 5'--P88, P52, P100--3'. The polypeptide P56, which we considered previously to be a primary product, is derived from the region of the genome that codes for P100. The results indicate that there are alternative cleavage pathways of P100, the polypeptide coded for by the 3' end of the genome.", "contents": "A re-appraisal of the biochemical map of foot-and-mouth disease virus RNA. The proteins induced by infection of BHK 21 cells with foot-and-mouth disease virus have been compared by tryptic peptide analysis. The results indicate that there are three primary products 5'--P88, P52, P100--3'. The polypeptide P56, which we considered previously to be a primary product, is derived from the region of the genome that codes for P100. The results indicate that there are alternative cleavage pathways of P100, the polypeptide coded for by the 3' end of the genome."}
{"id": "PMID:214523", "title": "Effect of interferon on transcription and translation of vesicular stomatitis virus in human and simian cell cultures.", "content": "The effect of interferons on vesicular stomatitis virus (VSV) primary transcription, amplified RNA synthesis [i.e. the sum of primary transcription RNA replication (leading to [ - ] RNA) and secondary transcription (leading to [ + ] RNA) and virus protein synthesis were studied. In a human cell line, both human and simian interferons inhibited the initiation of primary transcription and amplified RNA synthesis. In contrast, in a simian cell line tested similarly, the initiation of these activities was not affected, though they decreased as the infection progressed. Nevertheless, virus protein synthesis was completely inhibited. These results demonstrate that the action of interferon on virus transcription and/or translation may depend more on the host cell than on the particular interferon used.", "contents": "Effect of interferon on transcription and translation of vesicular stomatitis virus in human and simian cell cultures. The effect of interferons on vesicular stomatitis virus (VSV) primary transcription, amplified RNA synthesis [i.e. the sum of primary transcription RNA replication (leading to [ - ] RNA) and secondary transcription (leading to [ + ] RNA) and virus protein synthesis were studied. In a human cell line, both human and simian interferons inhibited the initiation of primary transcription and amplified RNA synthesis. In contrast, in a simian cell line tested similarly, the initiation of these activities was not affected, though they decreased as the infection progressed. Nevertheless, virus protein synthesis was completely inhibited. These results demonstrate that the action of interferon on virus transcription and/or translation may depend more on the host cell than on the particular interferon used."}
{"id": "PMID:214524", "title": "Synthesis of herpes simplex virus DNA in preparations of chromatin from infected cell nuclei.", "content": "Chromatin prepared from cells infected with Herpes simplex virus type 1 or type 2 can synthesize both virus and cell DNA in vitro. The rate of synthesis is comparable to that of isolated whole nuclei. Incorporation is limited, and both cell and virus DNA synthesis are sensitive to the presence of virus-specific antiserum and phosphonoacetate. In chromatin from cells infected with a phosphonoacetate resistant virus mutant, both types of DNA synthesis are resistant to the presence of the inhibitor.", "contents": "Synthesis of herpes simplex virus DNA in preparations of chromatin from infected cell nuclei. Chromatin prepared from cells infected with Herpes simplex virus type 1 or type 2 can synthesize both virus and cell DNA in vitro. The rate of synthesis is comparable to that of isolated whole nuclei. Incorporation is limited, and both cell and virus DNA synthesis are sensitive to the presence of virus-specific antiserum and phosphonoacetate. In chromatin from cells infected with a phosphonoacetate resistant virus mutant, both types of DNA synthesis are resistant to the presence of the inhibitor."}
{"id": "PMID:214525", "title": "The intracellular organization of actin and tubulin in cultured C-1300 mouse neuroblastoma cells (clone NB41A3).", "content": "Cells of clone NB41A3 of the C-1300 mouse neuroblastoma were grown to a critical density at which many of the cells flatten, assume a variety of shapes and sizes and some sprout processes resembling neurites. We have studied the distribution of actin and tubulin in these cells using fluorescence microscopy and antibodies against actin or tubulin under these conditions. Actin-containing structures are variably arranged and predominantly associated with motile areas of the cell periphery including the growth cone. Microtubules appear to run radially from the perinuclear area towards the cell periphery. When neurites are present, microtubules converge into them and run to the growth cone but rarely contact its edge.", "contents": "The intracellular organization of actin and tubulin in cultured C-1300 mouse neuroblastoma cells (clone NB41A3). Cells of clone NB41A3 of the C-1300 mouse neuroblastoma were grown to a critical density at which many of the cells flatten, assume a variety of shapes and sizes and some sprout processes resembling neurites. We have studied the distribution of actin and tubulin in these cells using fluorescence microscopy and antibodies against actin or tubulin under these conditions. Actin-containing structures are variably arranged and predominantly associated with motile areas of the cell periphery including the growth cone. Microtubules appear to run radially from the perinuclear area towards the cell periphery. When neurites are present, microtubules converge into them and run to the growth cone but rarely contact its edge."}
{"id": "PMID:214526", "title": "Correlations of Tc-99m pyrophosphate myocardial scintigraphy and the results of coronary-artery bypass surgery.", "content": "This study indicates that abnormal myocardial scintigrams with Tc-99m pyrophosphate tend to improve after coronary-artery bypass surgery, frequently changing from positive to normal. The significance of this change is uncertain. It does not correlate well with the clinical state but may simply reflect the natural course of myocardial scintigraphy in response to hospitalization, medical management, and presumably improved myocardial oxygenation. Postoperative myocardial scintigrams are useful in detecting perioperative infarction. ECG interpretation may be difficult in the immediate postoperative period and, in three cases, there were scintigraphic criteria of perioperative infarction without diagnostic changes on ECG. Patients with positive preoperative scintigrams, especially in association with Functional Class IV angina, are at increased risk during coronary-artery bypass surgery.", "contents": "Correlations of Tc-99m pyrophosphate myocardial scintigraphy and the results of coronary-artery bypass surgery. This study indicates that abnormal myocardial scintigrams with Tc-99m pyrophosphate tend to improve after coronary-artery bypass surgery, frequently changing from positive to normal. The significance of this change is uncertain. It does not correlate well with the clinical state but may simply reflect the natural course of myocardial scintigraphy in response to hospitalization, medical management, and presumably improved myocardial oxygenation. Postoperative myocardial scintigrams are useful in detecting perioperative infarction. ECG interpretation may be difficult in the immediate postoperative period and, in three cases, there were scintigraphic criteria of perioperative infarction without diagnostic changes on ECG. Patients with positive preoperative scintigrams, especially in association with Functional Class IV angina, are at increased risk during coronary-artery bypass surgery."}
{"id": "PMID:214527", "title": "The specificity of pyrophosphate myocardial scintigrams in patients with prior myocardial infarction: concise communication.", "content": "Fifty-five patients with old (9 days to 10 yr) transmural infarcts but with no evidence of recent infarction, were imaged with Tc-99m pyrophosphate. Discrete uptake was rare in the setting of an old infarct. Diffuse uptake was neither sensitive to, nor specific for, acute infarction. Prior infarction will rarely cause diagnostic error if the discrete pattern is required for a positive diagnosis.", "contents": "The specificity of pyrophosphate myocardial scintigrams in patients with prior myocardial infarction: concise communication. Fifty-five patients with old (9 days to 10 yr) transmural infarcts but with no evidence of recent infarction, were imaged with Tc-99m pyrophosphate. Discrete uptake was rare in the setting of an old infarct. Diffuse uptake was neither sensitive to, nor specific for, acute infarction. Prior infarction will rarely cause diagnostic error if the discrete pattern is required for a positive diagnosis."}
{"id": "PMID:214530", "title": "Ultrastructure of the lung in the rat following exposure to crocidolite asbestos and quartz.", "content": "Lung tissue from rats that had inhaled U.I.C.C. crocidolite asbestos or quartz particles showed thickening of the interstitial tissue and the presence of collagen fibres. Aggregates of macrophages in the alveolar spaces were a dominant feature of all the sections examined from asbestos exposed rats. According to the ultrastructural studies described here, all the macrophages were mature cells, indicating that the ingested crocidolite asbestos was non-toxic. Lung sections of rats exposed to quartz particles were significantly different. Single cells were found in the alveolar spaces and many macrophages showed a characteristic pattern of vacuole formation. Other cells contained intracellular membranous lamellated bodies, similar to those found in Type II pneumocytes. Cells containing lamellated bodies were also found in the interstitial tissue. These findings suggest that the two mineral dusts have quite different biological effects on the macrophage and that the development of pulmonary fibrosis may, to some extent, be caused by a different mechanism in each instance.", "contents": "Ultrastructure of the lung in the rat following exposure to crocidolite asbestos and quartz. Lung tissue from rats that had inhaled U.I.C.C. crocidolite asbestos or quartz particles showed thickening of the interstitial tissue and the presence of collagen fibres. Aggregates of macrophages in the alveolar spaces were a dominant feature of all the sections examined from asbestos exposed rats. According to the ultrastructural studies described here, all the macrophages were mature cells, indicating that the ingested crocidolite asbestos was non-toxic. Lung sections of rats exposed to quartz particles were significantly different. Single cells were found in the alveolar spaces and many macrophages showed a characteristic pattern of vacuole formation. Other cells contained intracellular membranous lamellated bodies, similar to those found in Type II pneumocytes. Cells containing lamellated bodies were also found in the interstitial tissue. These findings suggest that the two mineral dusts have quite different biological effects on the macrophage and that the development of pulmonary fibrosis may, to some extent, be caused by a different mechanism in each instance."}
{"id": "PMID:214531", "title": "Malignant synovioma: electron microscopical findings in three patients and review of the literature.", "content": "Ultrastructural findings in three malignant synoviomas are described. Two typical \"biphasic\" tumours contained \"epithelial\" cells possessing filopodia or microvilli, specialised cell attachment and a basal lamina, and smaller \"stromal\" cells showing transitions to fibroblasts. In one case, the microvilli included fibrils resembling those in epithelial cells of the intestine and renal tubules. The third tumour was mainly spindle-celled with little epithelial differentiation and no clear division into cell types, but intracytoplasmic microfibrils were conspicuous, forming ovoid masses. The tumour cells differ a good deal from normal human synovial cells but some of the features of the neoplasm are found in inflamed human synovium and in normal synovial membranes of other species. The cytoplasmic fibrils in the third case are similar to those reported by others in epithelioid sarcoma, a tumour that may be of related origin to synovioma; however, the phenomenon may be merely degenerative.", "contents": "Malignant synovioma: electron microscopical findings in three patients and review of the literature. Ultrastructural findings in three malignant synoviomas are described. Two typical \"biphasic\" tumours contained \"epithelial\" cells possessing filopodia or microvilli, specialised cell attachment and a basal lamina, and smaller \"stromal\" cells showing transitions to fibroblasts. In one case, the microvilli included fibrils resembling those in epithelial cells of the intestine and renal tubules. The third tumour was mainly spindle-celled with little epithelial differentiation and no clear division into cell types, but intracytoplasmic microfibrils were conspicuous, forming ovoid masses. The tumour cells differ a good deal from normal human synovial cells but some of the features of the neoplasm are found in inflamed human synovium and in normal synovial membranes of other species. The cytoplasmic fibrils in the third case are similar to those reported by others in epithelioid sarcoma, a tumour that may be of related origin to synovioma; however, the phenomenon may be merely degenerative."}
{"id": "PMID:214532", "title": "Pathological observations on experimental cytomegalovirus infections in pregnancy.", "content": "Cytomegalovirus injected intramuscularly or intraperitoneally into mice on the 8th day of pregnancy resulted in a significant retardation in foetal growth and a reduced number of offspring surviving until near-term. Pathological changes consisted of inflammatory cell infiltration in the liver, heart, salivary glands and adrenal cortex of affected animals. Necrotic changes were also present in the adrenal cortex in most severely affected animals following intraperitoneal injection of virus. Intraperitoneal infection led to a frank peritonitis and marked splenic necrosis with a degeneration and inflammation of visceral fatty tissue and lymphadenitis. In contrast, intramuscular injection of virus did not produce a peritonitis but the spleen was greatly enlarged with reaction centres and increased numbers of lymphocytes being identified at histology. As a consequence of cytomegalovirus infection in pregnant mice foetal growth impairment and intrauterine death was seen. This was related to the severity of pathological changes in the mothers. In those animals dying or appearing sick at near-term, most foetuses were dead and resorbing. Since murine cytomegalovirus was not identified by inclusion body formation in foetal or placental tissues in this study and virus has not been isolated from these tissues previously, it was concluded that the mechanism for the impaired foetal growth was of an indirect nature and attributable primarily to a severe generalised maternal illness.", "contents": "Pathological observations on experimental cytomegalovirus infections in pregnancy. Cytomegalovirus injected intramuscularly or intraperitoneally into mice on the 8th day of pregnancy resulted in a significant retardation in foetal growth and a reduced number of offspring surviving until near-term. Pathological changes consisted of inflammatory cell infiltration in the liver, heart, salivary glands and adrenal cortex of affected animals. Necrotic changes were also present in the adrenal cortex in most severely affected animals following intraperitoneal injection of virus. Intraperitoneal infection led to a frank peritonitis and marked splenic necrosis with a degeneration and inflammation of visceral fatty tissue and lymphadenitis. In contrast, intramuscular injection of virus did not produce a peritonitis but the spleen was greatly enlarged with reaction centres and increased numbers of lymphocytes being identified at histology. As a consequence of cytomegalovirus infection in pregnant mice foetal growth impairment and intrauterine death was seen. This was related to the severity of pathological changes in the mothers. In those animals dying or appearing sick at near-term, most foetuses were dead and resorbing. Since murine cytomegalovirus was not identified by inclusion body formation in foetal or placental tissues in this study and virus has not been isolated from these tissues previously, it was concluded that the mechanism for the impaired foetal growth was of an indirect nature and attributable primarily to a severe generalised maternal illness."}
{"id": "PMID:214534", "title": "Secretory antibody directed against rotavirus in human milk--measurement by means of enzyme-linked immunosorbent assay.", "content": "Human milk contains antibodies to a variety of enteropathic agents. We utilized the method of enzyme-linked immunosorbent assay to investigate anti-rotavirus secretory IgA in 113 human milk and colostral specimens from a rural area in Guatemala, 32 colostral specimens from an urban area of Costa Rica, and 12 from an urban area of the United States. Anti-rotavirus SCIgA was found in all colostral samples and in 94% of the milk specimans. Both the absolute concentration of anti-rotavirus SCIgA and concentration relative to total SCIgA were highest in colostrum, falling to lower but detectable levels from one week to two years after birth. No significant differences were noted in the results from the specimens from the three different geographic areas. The possible role of this antibody in immunity to rotavirus infections is discussed.", "contents": "Secretory antibody directed against rotavirus in human milk--measurement by means of enzyme-linked immunosorbent assay. Human milk contains antibodies to a variety of enteropathic agents. We utilized the method of enzyme-linked immunosorbent assay to investigate anti-rotavirus secretory IgA in 113 human milk and colostral specimens from a rural area in Guatemala, 32 colostral specimens from an urban area of Costa Rica, and 12 from an urban area of the United States. Anti-rotavirus SCIgA was found in all colostral samples and in 94% of the milk specimans. Both the absolute concentration of anti-rotavirus SCIgA and concentration relative to total SCIgA were highest in colostrum, falling to lower but detectable levels from one week to two years after birth. No significant differences were noted in the results from the specimens from the three different geographic areas. The possible role of this antibody in immunity to rotavirus infections is discussed."}
{"id": "PMID:214539", "title": "Immunologic studies on hamsters infected with Entamoeba histolytica.", "content": "The serologic and cell-mediated immune responses of hamsters exposed to 2 strains of Entamoeba histolytica (HM-1 and HM-19) were evaluated by a series of in vitro tests. The pathogenicity of the 2 strains was evaluated in terms of their ability to produce liver abscesses and spleen enlargement. Antibody response was evaluated by the indirect hemagglutination test. The cellular immune response was assayed by increased DNA synthesis by lymphocytes and migration inhibition of macrophages.", "contents": "Immunologic studies on hamsters infected with Entamoeba histolytica. The serologic and cell-mediated immune responses of hamsters exposed to 2 strains of Entamoeba histolytica (HM-1 and HM-19) were evaluated by a series of in vitro tests. The pathogenicity of the 2 strains was evaluated in terms of their ability to produce liver abscesses and spleen enlargement. Antibody response was evaluated by the indirect hemagglutination test. The cellular immune response was assayed by increased DNA synthesis by lymphocytes and migration inhibition of macrophages."}
{"id": "PMID:214541", "title": "Mesoionic xanthine analogs as inhibitors of cyclic AMP phosphodiesterase.", "content": "Several derivatives of two mesoionic xanthine analogs, mesoionic thiazolo[3,2-alpha]pyrimidine-5,7-diones and mesoionic 1,3,4-thiadiazolo[3,2-alpha]pyrimidine-5,7-diones, were synthesized and evaluated as inhibitors of cyclic AMP phosphodiesterase. A significant number of these compounds demonstrated theophylline-like activity.", "contents": "Mesoionic xanthine analogs as inhibitors of cyclic AMP phosphodiesterase. Several derivatives of two mesoionic xanthine analogs, mesoionic thiazolo[3,2-alpha]pyrimidine-5,7-diones and mesoionic 1,3,4-thiadiazolo[3,2-alpha]pyrimidine-5,7-diones, were synthesized and evaluated as inhibitors of cyclic AMP phosphodiesterase. A significant number of these compounds demonstrated theophylline-like activity."}
{"id": "PMID:214542", "title": "Formulation and evaluation of ethiodized oil emulsion for intravenous hepatography.", "content": "A study was conducted to prepare and evaluate an ethiodized oil emulsion for intravenous administration that would selectively opacify the liver. Several formulations with differing globule size were prepared and compared for their in vivo activity (degree of liver opacification obtained) and stability. Results of studies conducted in rabbits and monkeys revealed that the oil globules that concentrate most in liver were 2.0--3.0 micrometer in diameter. The formulation of choice was stable for 6 months at refrigeration temperature (2--6 degree). In monkeys, this formulation produced an improved diagnostic image of the liver using computerized tomography at a dose of 0.2 ml/kg. The potential use of such emulsions in diagnostic radiology is briefly discussed.", "contents": "Formulation and evaluation of ethiodized oil emulsion for intravenous hepatography. A study was conducted to prepare and evaluate an ethiodized oil emulsion for intravenous administration that would selectively opacify the liver. Several formulations with differing globule size were prepared and compared for their in vivo activity (degree of liver opacification obtained) and stability. Results of studies conducted in rabbits and monkeys revealed that the oil globules that concentrate most in liver were 2.0--3.0 micrometer in diameter. The formulation of choice was stable for 6 months at refrigeration temperature (2--6 degree). In monkeys, this formulation produced an improved diagnostic image of the liver using computerized tomography at a dose of 0.2 ml/kg. The potential use of such emulsions in diagnostic radiology is briefly discussed."}
{"id": "PMID:214543", "title": "Glutamate current noise: post-synaptic channel kinetics investigated under voltage clamp.", "content": "1. Analysis of voltage-clamped noise has been used to investigate the operation of glutamate receptors and associated channels at the locust nerve-muscle junction. Channels opened by glutamate and an agonist have been compared. 2. Glutamate-induced current fluctuations have a power spectrum with a single (1/frequency2) component which fits a simple model for the operation of channels. The form of the spectra for glutamate voltage noise and for 'background' noise has been determined. 3. The single channel conductance was estimated from the spectra, gamma glutamate = 122 +/- 0.4 (S.E.) pS. This estimate is independent of membrane potential and of the amplitude of membrane current change produced by glutamate. 4. The rate constant, alpha, for the closing of glutamate-operated channels depends exponentially on membrane potential, conforming to the equation alpha = approximately alphaeetaVm (approximately alpha = 0.26 +/- 0.014 msec-1, eta = 0.0054 +/- 0.001 msec-1); the duration of the channel lifetime (tau) decreases with hyperpolarization. Membrane potential dependence of alpha reduces as temperature is lowered. 5. For glutamate-operated channels, the temperature dependence of alpha and gamma fits the Arrhenius equation; alpha and gamma decrease exponentially as a function of T-1 (degrees K) with a descrete change in slope at about 6 degrees C, indicating a change in the activaiton energies of the respective rate processes. 6. Spectra of quisqualate-induced current fluctuations have the same form as spectra for glutamate noise. The single channel conductance was estimated from the spectra, gamma quisqualate = 120 +/- 3.9 (S.E.) pS. 7. The rate constnt, alpha, for the closing of quisqualate-induced channels depends exponentially on membrane potential. The duration of the open state for quisqualate channels was 2.2 times longer than for glutamate channels. 8. For glutamate receptors the voltage-sensitivity of the channel life-time is in the opposite direction to that of ACh receptors in vertebrate muscle. Possible explanations for the sharp change in the activation energy of the rate processes associated with the channel are discussed.", "contents": "Glutamate current noise: post-synaptic channel kinetics investigated under voltage clamp. 1. Analysis of voltage-clamped noise has been used to investigate the operation of glutamate receptors and associated channels at the locust nerve-muscle junction. Channels opened by glutamate and an agonist have been compared. 2. Glutamate-induced current fluctuations have a power spectrum with a single (1/frequency2) component which fits a simple model for the operation of channels. The form of the spectra for glutamate voltage noise and for 'background' noise has been determined. 3. The single channel conductance was estimated from the spectra, gamma glutamate = 122 +/- 0.4 (S.E.) pS. This estimate is independent of membrane potential and of the amplitude of membrane current change produced by glutamate. 4. The rate constant, alpha, for the closing of glutamate-operated channels depends exponentially on membrane potential, conforming to the equation alpha = approximately alphaeetaVm (approximately alpha = 0.26 +/- 0.014 msec-1, eta = 0.0054 +/- 0.001 msec-1); the duration of the channel lifetime (tau) decreases with hyperpolarization. Membrane potential dependence of alpha reduces as temperature is lowered. 5. For glutamate-operated channels, the temperature dependence of alpha and gamma fits the Arrhenius equation; alpha and gamma decrease exponentially as a function of T-1 (degrees K) with a descrete change in slope at about 6 degrees C, indicating a change in the activaiton energies of the respective rate processes. 6. Spectra of quisqualate-induced current fluctuations have the same form as spectra for glutamate noise. The single channel conductance was estimated from the spectra, gamma quisqualate = 120 +/- 3.9 (S.E.) pS. 7. The rate constnt, alpha, for the closing of quisqualate-induced channels depends exponentially on membrane potential. The duration of the open state for quisqualate channels was 2.2 times longer than for glutamate channels. 8. For glutamate receptors the voltage-sensitivity of the channel life-time is in the opposite direction to that of ACh receptors in vertebrate muscle. Possible explanations for the sharp change in the activation energy of the rate processes associated with the channel are discussed."}
{"id": "PMID:214544", "title": "The tract of Lissauer and the dorsal root potential.", "content": "1. Intersegmental dorsal root potentials (d.r.p.s) have been recorded in the lumbar spinal cord of spinalized cats under Na pentobarbitone anaesthesia, to investigate the spinal cord structures involved in the intersegmental transmission of d.r.p.s. 2. A technique has been developed for restricted surgical isolation of Lissauer's tract between the segments with subsequent histological verification of the extent of the isolation. 3. Section of the ipsilateral dorsal column resulted in an increase in the latency of the intersegmental d.r.p. and a significant reduction in its amplitude. A further reduction in amplitude was achieved by section of the ipsilateral dorso-lateral funiculus. 4. Neither section of Lissauer's tract after the above lesions were performed nor restricted Lissauer's tractotomies abolished intersegmental d.r.p.s; only a small reduction in the amplitude of the d.r.p. was obtained. 5. It is proposed that intersegmental d.r.p.s are produced by the activaiton of a propriospinal system projecting through pathways other than Lissauer's tract and that primary afferent collaterals from the dorsal columns make a major contribtuion to their generation. The contribution made by Lissauer's tract is probably small.", "contents": "The tract of Lissauer and the dorsal root potential. 1. Intersegmental dorsal root potentials (d.r.p.s) have been recorded in the lumbar spinal cord of spinalized cats under Na pentobarbitone anaesthesia, to investigate the spinal cord structures involved in the intersegmental transmission of d.r.p.s. 2. A technique has been developed for restricted surgical isolation of Lissauer's tract between the segments with subsequent histological verification of the extent of the isolation. 3. Section of the ipsilateral dorsal column resulted in an increase in the latency of the intersegmental d.r.p. and a significant reduction in its amplitude. A further reduction in amplitude was achieved by section of the ipsilateral dorso-lateral funiculus. 4. Neither section of Lissauer's tract after the above lesions were performed nor restricted Lissauer's tractotomies abolished intersegmental d.r.p.s; only a small reduction in the amplitude of the d.r.p. was obtained. 5. It is proposed that intersegmental d.r.p.s are produced by the activaiton of a propriospinal system projecting through pathways other than Lissauer's tract and that primary afferent collaterals from the dorsal columns make a major contribtuion to their generation. The contribution made by Lissauer's tract is probably small."}
{"id": "PMID:214546", "title": "Spontaneous multiquantal release at synapses in guinea-pig hypogastric ganglia: evidence that release can occur in bursts.", "content": "1. A study was made of some properties of the spontaneous synaptic potentials recorded in cells of the hypogastric ganglia of guinea-pigs. 2. The distribution of the amplitudes of the spontaneous synaptic potentials arising from a single preganglionic fibre was found to be multimodal, with peaks at roughly integral multiples of a unit peak. 3. It was found that the amplitudes of the larger spontaneous potentials were consistent with them being the result of synchronous or near-synchronous release of two or more unit-sized quanta (multiquantal release). 4. The proportion of multiquantal potentials observed was found to be dependent on the extracellular calcium ion concentration. 5. When the stochastic properties of the spontaneous potentials were examined, it was found that the spontaneous release process was not random and independent but appeared to be clustered. Indeed, the probability of occurrence of a unit spontaneous synaptic potential was greatly enhanced during the 40--60 msec immediately following any given spontaneous synaptic potential. 6. When unit spontaneous potentials were excluded from the analysis, the multiquantal potentials were still found to be clustered although the clustering was less marked than that seen in the over-all process. 7. These results suggested that the multiquantal spontaneous potentials arose from the release of unit quanta in short high frequency bursts and it was found that a mathematical model incorporating such a mechanism could describe the spontaneous quantal release process.", "contents": "Spontaneous multiquantal release at synapses in guinea-pig hypogastric ganglia: evidence that release can occur in bursts. 1. A study was made of some properties of the spontaneous synaptic potentials recorded in cells of the hypogastric ganglia of guinea-pigs. 2. The distribution of the amplitudes of the spontaneous synaptic potentials arising from a single preganglionic fibre was found to be multimodal, with peaks at roughly integral multiples of a unit peak. 3. It was found that the amplitudes of the larger spontaneous potentials were consistent with them being the result of synchronous or near-synchronous release of two or more unit-sized quanta (multiquantal release). 4. The proportion of multiquantal potentials observed was found to be dependent on the extracellular calcium ion concentration. 5. When the stochastic properties of the spontaneous potentials were examined, it was found that the spontaneous release process was not random and independent but appeared to be clustered. Indeed, the probability of occurrence of a unit spontaneous synaptic potential was greatly enhanced during the 40--60 msec immediately following any given spontaneous synaptic potential. 6. When unit spontaneous potentials were excluded from the analysis, the multiquantal potentials were still found to be clustered although the clustering was less marked than that seen in the over-all process. 7. These results suggested that the multiquantal spontaneous potentials arose from the release of unit quanta in short high frequency bursts and it was found that a mathematical model incorporating such a mechanism could describe the spontaneous quantal release process."}
{"id": "PMID:214547", "title": "Dopamine receptors in the central thermoregulatory pathways of the rat.", "content": "1. Intrahypothalamic injection of either dopamine (10 microgram) or apomorphine (10 microgram) in a dose volume of 1 microliter. caused an almost immediate rise in tail skin temperature and a concomitant fall in core temperature in the conscious rat maintained at an ambient temperature of 17 +/- 1 degrees C. 2. The location of the dopamine-sensitive site was defined more accurately by reducing the dose volume to 0.5 microliter. and injecting dopamine at different points throughout the preoptic and anterior hypothalamic region. 3. The largest mean fall in core temperature (1.13 +/- 0.22 degrees C) was obtained after injection into the preoptic region. Injections with their perimeters more than 0.4 mm rostral or caudal to this site were ineffective. 4. Rats placed 0.65 m below a 250 W infra-red lamp responded to the imposed heat load by vasodilation of the tail skin blood vessels, indicated by an increased tail skin temperature. 5. Bilateral, but not unilateral, injection of either pimozide (0.5 microgram) or haloperidol (2.5 microgram) into the preoptic region significantly reduced the increase in tail skin temperature so that the rats were less able to withstand the imposed heat load. 6. Three serial sections (0.5 mm thick) were prepared from the preoptic anterior hypothalamic region of the rat brain, one anterior, one posterior and one corresponding to the dopamine-sensitive site. 7. Tissue from the middle slice increased its rate of synthesis of 3,5-cyclic AMP in response to addition of dopamine 20 or 100 micron to the incubation medium. The posterior slice was inactive, but the anterior slice had similar activity to the middle slice. 8. The effect of dopamine on the middle slice was specifically blocked by haloperidol (0.1 micron), whereas the effects on the anterior slice were partially blocked by both haloperidol (0.1 micron) and propranolol (0.1 micron). 9. These results indicate that there is within a well defined area of the preoptic region a population of dopamine receptors, which play a part in the transmission of information from warm sensors to heat loss effectors.", "contents": "Dopamine receptors in the central thermoregulatory pathways of the rat. 1. Intrahypothalamic injection of either dopamine (10 microgram) or apomorphine (10 microgram) in a dose volume of 1 microliter. caused an almost immediate rise in tail skin temperature and a concomitant fall in core temperature in the conscious rat maintained at an ambient temperature of 17 +/- 1 degrees C. 2. The location of the dopamine-sensitive site was defined more accurately by reducing the dose volume to 0.5 microliter. and injecting dopamine at different points throughout the preoptic and anterior hypothalamic region. 3. The largest mean fall in core temperature (1.13 +/- 0.22 degrees C) was obtained after injection into the preoptic region. Injections with their perimeters more than 0.4 mm rostral or caudal to this site were ineffective. 4. Rats placed 0.65 m below a 250 W infra-red lamp responded to the imposed heat load by vasodilation of the tail skin blood vessels, indicated by an increased tail skin temperature. 5. Bilateral, but not unilateral, injection of either pimozide (0.5 microgram) or haloperidol (2.5 microgram) into the preoptic region significantly reduced the increase in tail skin temperature so that the rats were less able to withstand the imposed heat load. 6. Three serial sections (0.5 mm thick) were prepared from the preoptic anterior hypothalamic region of the rat brain, one anterior, one posterior and one corresponding to the dopamine-sensitive site. 7. Tissue from the middle slice increased its rate of synthesis of 3,5-cyclic AMP in response to addition of dopamine 20 or 100 micron to the incubation medium. The posterior slice was inactive, but the anterior slice had similar activity to the middle slice. 8. The effect of dopamine on the middle slice was specifically blocked by haloperidol (0.1 micron), whereas the effects on the anterior slice were partially blocked by both haloperidol (0.1 micron) and propranolol (0.1 micron). 9. These results indicate that there is within a well defined area of the preoptic region a population of dopamine receptors, which play a part in the transmission of information from warm sensors to heat loss effectors."}
{"id": "PMID:214549", "title": "Propriospinal neurones as a relay system for transmission of cortico-spinal influences.", "content": "1. Synaptic organization and transmission have been studied in the lateral group of short propriospinal neurones of the lumbar and cervical regions of the cat spinal cord. Special attention was paid to their role in the transmission of cortico-spinal volleys. 2. The majority of these neurones are mono- or oligosynaptically excited after pyramidal tract stimulation. Convergence of excitatory actions from rubrospinal and lateral reticulospinal tracts was typical for these cells. Neurones with relatively low-level and delayed effects from segmental afferents are frequent in this population. 3. Temporal summation is important for the transmission of descending vlleys through these neurones. Mutual excitatory and recurrent inhibitory connections are supposed to play a substantial role in their function. 4. Possible participation of the short lateral propriospinal system in the transmission, transformation and re-distribution of corticofugal signals to the segmental spinal mechanisms is discussed.", "contents": "Propriospinal neurones as a relay system for transmission of cortico-spinal influences. 1. Synaptic organization and transmission have been studied in the lateral group of short propriospinal neurones of the lumbar and cervical regions of the cat spinal cord. Special attention was paid to their role in the transmission of cortico-spinal volleys. 2. The majority of these neurones are mono- or oligosynaptically excited after pyramidal tract stimulation. Convergence of excitatory actions from rubrospinal and lateral reticulospinal tracts was typical for these cells. Neurones with relatively low-level and delayed effects from segmental afferents are frequent in this population. 3. Temporal summation is important for the transmission of descending vlleys through these neurones. Mutual excitatory and recurrent inhibitory connections are supposed to play a substantial role in their function. 4. Possible participation of the short lateral propriospinal system in the transmission, transformation and re-distribution of corticofugal signals to the segmental spinal mechanisms is discussed."}
{"id": "PMID:214548", "title": "The effect of pituitary-adrenal function in the modulation of pain sensitivity in the rat.", "content": "1. The relationship between adrenalcortical hormones, adrenocorticotrophic hormone (ACTH), and pain sensitivity was investigated in the rat. Pain sensitivity was assessed by measuring paw-lick and jump latencies in response to being placed on a grid at 55 degrees C.2. Bilateral adrenalectomy increased the sensitivity to pain, but adrenal demedullation had no effect.3. Pain sensitivity was inversely related to the circadian changes in circulating corticosterone and was greater at 7 a.m. than at 7 p.m. However, the same variation in pain sensitivity existed if the adrenals were removed, suggesting that the increase in pain sensitivity after adrenalectomy was not related directly to the levels of corticosteriods.4. The time course of the increase in pain sensitivity after adrenalectomy paralleled that of the changes in circulating ACTH. Adrenalectomy markedly increased pain sensitivity at 9 and 18 days following surgery when circulating ACTH levels were markedly elevated and corticosterone was absent, but not at 3 days following adrenalectomy when ACTH levels were lower and corticosterone was absent.5. Hypophysectomy decreased the sensitivity to pain.6. The results indicate that ACTH can alter pain sensitivity and that the effect of corticosteroids on the sensitivity to pain is an indirect one by virtue of their negative feed-back action on the hypothalamic-pituitary system.", "contents": "The effect of pituitary-adrenal function in the modulation of pain sensitivity in the rat. 1. The relationship between adrenalcortical hormones, adrenocorticotrophic hormone (ACTH), and pain sensitivity was investigated in the rat. Pain sensitivity was assessed by measuring paw-lick and jump latencies in response to being placed on a grid at 55 degrees C.2. Bilateral adrenalectomy increased the sensitivity to pain, but adrenal demedullation had no effect.3. Pain sensitivity was inversely related to the circadian changes in circulating corticosterone and was greater at 7 a.m. than at 7 p.m. However, the same variation in pain sensitivity existed if the adrenals were removed, suggesting that the increase in pain sensitivity after adrenalectomy was not related directly to the levels of corticosteriods.4. The time course of the increase in pain sensitivity after adrenalectomy paralleled that of the changes in circulating ACTH. Adrenalectomy markedly increased pain sensitivity at 9 and 18 days following surgery when circulating ACTH levels were markedly elevated and corticosterone was absent, but not at 3 days following adrenalectomy when ACTH levels were lower and corticosterone was absent.5. Hypophysectomy decreased the sensitivity to pain.6. The results indicate that ACTH can alter pain sensitivity and that the effect of corticosteroids on the sensitivity to pain is an indirect one by virtue of their negative feed-back action on the hypothalamic-pituitary system."}
{"id": "PMID:214551", "title": "Ultrastructural and cytochemical observations on sporogenesis of Myxobolus sp. (Myxosporida: Myxobolidae) from the common shiner Notropis cornutus.", "content": "The structure and cytochemistry of spores of Myxobolus sp. from plasmodia which occur in the gill filaments of the common shiner Notropis cornutus were studied by light microscopy and by scanning and transmission electron microscopy. The thin-walled valves of the pyriform spores are thickened in the lateral sutural and apical regions. Mucous material is associated predominantly with the posterior end of many spores. The plasmodium is surrounded by a syncytial wall bounded by 2 membranes. Pinocytotic channels are formed by the inner membrane and numerous dense vesicles are pinched off at the distal ends of the channels. Sporogenesis is initiated by the envelopment of one vegetative cell by another. The larger, enveloped cell divides to form a disporous pansporoblast, which contains 2 pairs of capsulogenic and valvogenic cells and 2 binucleate sporoplasm cells. Each capsular primordium and connecting external tubule gives rise to a polar capsule which houses a helically coiled polar tubule. The apical end of each polar capsule is plugged by a stopper. The valvogenic cells surround the capsulogenic and posteriorly situated sporoplasm cells to form the spore valves. Iodinophilic (glycogen) inclusions were not seen in spores stained with iodine or Best's carmine. A darkly stained band was observed around the posterior region of most spores stained with Best's carmine. In the electron microscope large aggregates of beta glycogen particles were seen in the cytoplasm of sporoplasm cells in mature spores.", "contents": "Ultrastructural and cytochemical observations on sporogenesis of Myxobolus sp. (Myxosporida: Myxobolidae) from the common shiner Notropis cornutus. The structure and cytochemistry of spores of Myxobolus sp. from plasmodia which occur in the gill filaments of the common shiner Notropis cornutus were studied by light microscopy and by scanning and transmission electron microscopy. The thin-walled valves of the pyriform spores are thickened in the lateral sutural and apical regions. Mucous material is associated predominantly with the posterior end of many spores. The plasmodium is surrounded by a syncytial wall bounded by 2 membranes. Pinocytotic channels are formed by the inner membrane and numerous dense vesicles are pinched off at the distal ends of the channels. Sporogenesis is initiated by the envelopment of one vegetative cell by another. The larger, enveloped cell divides to form a disporous pansporoblast, which contains 2 pairs of capsulogenic and valvogenic cells and 2 binucleate sporoplasm cells. Each capsular primordium and connecting external tubule gives rise to a polar capsule which houses a helically coiled polar tubule. The apical end of each polar capsule is plugged by a stopper. The valvogenic cells surround the capsulogenic and posteriorly situated sporoplasm cells to form the spore valves. Iodinophilic (glycogen) inclusions were not seen in spores stained with iodine or Best's carmine. A darkly stained band was observed around the posterior region of most spores stained with Best's carmine. In the electron microscope large aggregates of beta glycogen particles were seen in the cytoplasm of sporoplasm cells in mature spores."}
{"id": "PMID:214552", "title": "11,12-Secoprostaglandins. 5. 8-Acetyl- or 8-(1-hydroxyethyl)-12-hydroxy-13-aryloxytridecanoic acids and sulfonamide isosteres as inhibitors of platelet aggregation.", "content": "The synthesis of a series of 8-acetyl- (or 1-hydroxyethyl-) 12-hydroxy-13-aryloxytridecanoic acids and their sulfonamide isosteres is described. These compounds are formally derived from members of earlier reported series of modified secoprostaglandins by replacing the omega-butyl chain termini by substituted aryloxy groups. A number of these compounds are potent inhibitors of collagen-induced blood platelet aggregation in guinea pigs on oral administration.", "contents": "11,12-Secoprostaglandins. 5. 8-Acetyl- or 8-(1-hydroxyethyl)-12-hydroxy-13-aryloxytridecanoic acids and sulfonamide isosteres as inhibitors of platelet aggregation. The synthesis of a series of 8-acetyl- (or 1-hydroxyethyl-) 12-hydroxy-13-aryloxytridecanoic acids and their sulfonamide isosteres is described. These compounds are formally derived from members of earlier reported series of modified secoprostaglandins by replacing the omega-butyl chain termini by substituted aryloxy groups. A number of these compounds are potent inhibitors of collagen-induced blood platelet aggregation in guinea pigs on oral administration."}
{"id": "PMID:214554", "title": "Synthesis, opiate receptor affinity, and conformational parameters of [4-tryptophan]enkephalin analogues.", "content": "A series of analogues of the opioid peptide enkephalin with tryptophan substituted for phenylalanine in position 4 was synthesized by the solid-phase method. The [Trp4]enkephalin analogues and the corresponding [Phe4]enkephalin analogues displayed nearly parallel affinities in the opiate receptor binding assay throughout the series. In a conformational study fluorescence parameters were measured and intramolecular Tyr-Trp distances were estimated on the basis of resonance energy transfer experiments. No gross conformational differences were observed between analogues with widely differing opiate receptor affinity; however, small but significant changes in the intramolecular distance between the phenol ring and the indole moiety and/or in their relative orientation became apparent in some compounds. Identical intramolecular distances of 9.3 +/- 0.2 angstrom between the two aromatic rings were obtained with [Trp4,Met5]enkephalin, [Trp4,Leu5]enkephalin, and the N-terminal tetrapeptide comprised in the latter two analogues, indicating the existence of folded conformationas in 2 X 10(-5) M aqueous solution and demonstrating conformational analogy between these three peptides. The conformational parameters are discussed in relation to the observed affinities and the putative opiate receptor topography.", "contents": "Synthesis, opiate receptor affinity, and conformational parameters of [4-tryptophan]enkephalin analogues. A series of analogues of the opioid peptide enkephalin with tryptophan substituted for phenylalanine in position 4 was synthesized by the solid-phase method. The [Trp4]enkephalin analogues and the corresponding [Phe4]enkephalin analogues displayed nearly parallel affinities in the opiate receptor binding assay throughout the series. In a conformational study fluorescence parameters were measured and intramolecular Tyr-Trp distances were estimated on the basis of resonance energy transfer experiments. No gross conformational differences were observed between analogues with widely differing opiate receptor affinity; however, small but significant changes in the intramolecular distance between the phenol ring and the indole moiety and/or in their relative orientation became apparent in some compounds. Identical intramolecular distances of 9.3 +/- 0.2 angstrom between the two aromatic rings were obtained with [Trp4,Met5]enkephalin, [Trp4,Leu5]enkephalin, and the N-terminal tetrapeptide comprised in the latter two analogues, indicating the existence of folded conformationas in 2 X 10(-5) M aqueous solution and demonstrating conformational analogy between these three peptides. The conformational parameters are discussed in relation to the observed affinities and the putative opiate receptor topography."}
{"id": "PMID:214555", "title": "Synthesis and biological activities of some uronic acids, uronates, uronamides, and urononitriles of pyrimidine nucleosides.", "content": "The 5'-hydroxymethylene function of several uracil and cytosine nucleosides has been modified to produce a variety of uronic acids, uronates, uronamides, and urononitriles of 2'-deoxy-beta-D-erythro-pentofuranosyl- and beta-D-arabino-pentofuranosylpyrimidines. In addition, the 5 position in many of these nucleosides has been substituted by a halogen atom. Twenty-one of the 35 compounds synthesized and examined for biological activity have not been previously reported. The purity of the products was measured by a high-pressure liquid chromatographic method. They were then evaluated as potential growth inhibitors of murine Sarcoma 180 cells in culture, of herpes simplex virus type 1 in vitro, and of Streptococcus faecium, a folic acid or deoxythymidine dependent bacterial strain. The ability of these nucleoside analogues to inhibit the phosphorylation of deoxythymidine by herpes simplex virus type 1 encoded pyrimidine deoxyribonucleoside kinase was also investigated and a structure-activity relationship examined.", "contents": "Synthesis and biological activities of some uronic acids, uronates, uronamides, and urononitriles of pyrimidine nucleosides. The 5'-hydroxymethylene function of several uracil and cytosine nucleosides has been modified to produce a variety of uronic acids, uronates, uronamides, and urononitriles of 2'-deoxy-beta-D-erythro-pentofuranosyl- and beta-D-arabino-pentofuranosylpyrimidines. In addition, the 5 position in many of these nucleosides has been substituted by a halogen atom. Twenty-one of the 35 compounds synthesized and examined for biological activity have not been previously reported. The purity of the products was measured by a high-pressure liquid chromatographic method. They were then evaluated as potential growth inhibitors of murine Sarcoma 180 cells in culture, of herpes simplex virus type 1 in vitro, and of Streptococcus faecium, a folic acid or deoxythymidine dependent bacterial strain. The ability of these nucleoside analogues to inhibit the phosphorylation of deoxythymidine by herpes simplex virus type 1 encoded pyrimidine deoxyribonucleoside kinase was also investigated and a structure-activity relationship examined."}
{"id": "PMID:214556", "title": "Potential bis-alkylating agents for cancer chemotherapy. Approaches to the synthesis of 2-sulfonyl-1,4-bis(methanesulfonoxy)butanes.", "content": "Three general methods for the synthesis of derivatives of the bis-alkylating agent, myleran [1,4-bis(methane-sulfonoxy)butane (1)], are presented. These derivatives contain a lipophilic group attached to the 2 position of 1,4-bis(methanesulfonoxy)butane by means of a sulfonyl function. As examples of the scope of the methods, the synthesis of seven such derivatives (12a-g) is presented. All seven were inactive against L1210 and P388 leukemia in the mouse.", "contents": "Potential bis-alkylating agents for cancer chemotherapy. Approaches to the synthesis of 2-sulfonyl-1,4-bis(methanesulfonoxy)butanes. Three general methods for the synthesis of derivatives of the bis-alkylating agent, myleran [1,4-bis(methane-sulfonoxy)butane (1)], are presented. These derivatives contain a lipophilic group attached to the 2 position of 1,4-bis(methanesulfonoxy)butane by means of a sulfonyl function. As examples of the scope of the methods, the synthesis of seven such derivatives (12a-g) is presented. All seven were inactive against L1210 and P388 leukemia in the mouse."}
{"id": "PMID:214557", "title": "Synthesis and some pharmacological properties of the 23-peptide 15-lysine-secretin-(5--27). Special role of the residue in position 15 in biological activity of the vasoactive intestinal polypeptide.", "content": "The 23-peptide 15-lysine-secretin-(5-27) [S(5-27)] was synthesized on an insoluble support. The residue in position 15 of secretin, aspartic acid, was replaced by lysine, which occupies that position in the vasoactive intestinal polypeptide (VIP), a member of the secretin family. The resulting analogue showed increased VIP-like activity on smooth muscle preparations and unaltered secretin-like activity on pancreatic juice secretion in the rat. The affinity of the new analogue was high-affinity secretin receptors in acinar cells from guinea pig pancreas was less than that of S(5-27) but was higher than that of S(5-27) for high-affinity VIP receptors in the same cells.", "contents": "Synthesis and some pharmacological properties of the 23-peptide 15-lysine-secretin-(5--27). Special role of the residue in position 15 in biological activity of the vasoactive intestinal polypeptide. The 23-peptide 15-lysine-secretin-(5-27) [S(5-27)] was synthesized on an insoluble support. The residue in position 15 of secretin, aspartic acid, was replaced by lysine, which occupies that position in the vasoactive intestinal polypeptide (VIP), a member of the secretin family. The resulting analogue showed increased VIP-like activity on smooth muscle preparations and unaltered secretin-like activity on pancreatic juice secretion in the rat. The affinity of the new analogue was high-affinity secretin receptors in acinar cells from guinea pig pancreas was less than that of S(5-27) but was higher than that of S(5-27) for high-affinity VIP receptors in the same cells."}
{"id": "PMID:214558", "title": "Collagenase-sensitive peptidyl-nitrogen mustards as potential antitumor agents.", "content": "Attempts to design an agent which would release cytotoxic nitrogen mustards within collagenase-producing tumors led to the synthesis of Cbz-L-Pro-L-Leu-Gly-L-Pro-Gly-NHC6H4N(CH2CH2Cl)2 (10). 10 was cleaved in vitro by bacterial and tumor-associated collagenase as expected at the peptide bond joining L-leucine and glycine to give Gly-L-Pro-Gly-NHC6H4N(CH2CH2Cl)2 which was over six times more toxic, on a molar basis, than 10. In vivo tests of 10 against well-advanced Sarcoma-180 gave disappointing results. The lack of specific antitumor activity may be accounted for by the presence of competing cleavage reactions by collagenases in certain normal tissues.", "contents": "Collagenase-sensitive peptidyl-nitrogen mustards as potential antitumor agents. Attempts to design an agent which would release cytotoxic nitrogen mustards within collagenase-producing tumors led to the synthesis of Cbz-L-Pro-L-Leu-Gly-L-Pro-Gly-NHC6H4N(CH2CH2Cl)2 (10). 10 was cleaved in vitro by bacterial and tumor-associated collagenase as expected at the peptide bond joining L-leucine and glycine to give Gly-L-Pro-Gly-NHC6H4N(CH2CH2Cl)2 which was over six times more toxic, on a molar basis, than 10. In vivo tests of 10 against well-advanced Sarcoma-180 gave disappointing results. The lack of specific antitumor activity may be accounted for by the presence of competing cleavage reactions by collagenases in certain normal tissues."}
{"id": "PMID:214561", "title": "Inhibition of beef-brain and dog-heart (Na+ + k+) activated adenosine triphosphatase by carbon-3 branched cardenolides.", "content": "Twenty-two C-3 branched cardenolides were investigated as inhibitors of beef-brain and dog-heart (Na+ + k+) activated adenosine triphosphatase. The synthetic compounds had lower inhibitory strength than digitoxigenin, and there was no indication of an improved safety index. Structure--activity relationships show that increased steric shielding of the 3-OH group results in reduced inhibition.", "contents": "Inhibition of beef-brain and dog-heart (Na+ + k+) activated adenosine triphosphatase by carbon-3 branched cardenolides. Twenty-two C-3 branched cardenolides were investigated as inhibitors of beef-brain and dog-heart (Na+ + k+) activated adenosine triphosphatase. The synthetic compounds had lower inhibitory strength than digitoxigenin, and there was no indication of an improved safety index. Structure--activity relationships show that increased steric shielding of the 3-OH group results in reduced inhibition."}
{"id": "PMID:214562", "title": "Photoaffinity labeling of the angiotensin II receptor. 1. Synthesis and biological activities of the labeling peptides.", "content": "The synthesis and biological activities of analogues of the peptide hormone angiotensin II (AT) for use in photoaffinity labeling and receptor isolation are described. In the modified sequence of AT, Sar-Arg-Val-Tyr-Val-His-Pro-Phe, the aromatic residues Tyr and Phe have been either singly or simultaneously replaced by L-4'-nitrophenylalanine, L-4'-amino-3',5'-diiodophenylalanine, L-4'-aminophenylalanine, L-4'-diazoniumphenylalanine, and L-4'-azidophenylalanine. The peptides were assembled by solid-phase synthesis and the functional groups in position 4 and/or 8 chemically modified. Radioactivity was introduced by catalytic tritiation of the iodinated peptides to form the photolabeling precursors containing L-4'-amino-3',5'-diiodophenylalanine. On rabbit aorta the AT analogues substituted in position 4 showed poor affinities (0--15%), in position 8 high relative affinities (16--118%), and in position 4 and 8 additive effects of simultaneous substitutions. It is also shown that the new Boc derivative of L-4'-amino-3',5'-diiodophenylalanine can be used in peptide synthesis without side-chain protection.", "contents": "Photoaffinity labeling of the angiotensin II receptor. 1. Synthesis and biological activities of the labeling peptides. The synthesis and biological activities of analogues of the peptide hormone angiotensin II (AT) for use in photoaffinity labeling and receptor isolation are described. In the modified sequence of AT, Sar-Arg-Val-Tyr-Val-His-Pro-Phe, the aromatic residues Tyr and Phe have been either singly or simultaneously replaced by L-4'-nitrophenylalanine, L-4'-amino-3',5'-diiodophenylalanine, L-4'-aminophenylalanine, L-4'-diazoniumphenylalanine, and L-4'-azidophenylalanine. The peptides were assembled by solid-phase synthesis and the functional groups in position 4 and/or 8 chemically modified. Radioactivity was introduced by catalytic tritiation of the iodinated peptides to form the photolabeling precursors containing L-4'-amino-3',5'-diiodophenylalanine. On rabbit aorta the AT analogues substituted in position 4 showed poor affinities (0--15%), in position 8 high relative affinities (16--118%), and in position 4 and 8 additive effects of simultaneous substitutions. It is also shown that the new Boc derivative of L-4'-amino-3',5'-diiodophenylalanine can be used in peptide synthesis without side-chain protection."}
{"id": "PMID:214563", "title": "Imidazo[1,2-a]-s-triazine nucleosides. Synthesis and antiviral activity of the N-bridgehead guanine, guanosine, and guanosine monophosphate analogues of imidazo[1,2-a]-s-triazine.", "content": "The first chemical synthesis of 2-aminoimidazo[1,2-a]-s-triazin-4-one (8), the corresponding nucleoside and nucleotide, and certain related derivatives of a new class of purine analogues containing a bridgehead nitrogen atom is described. Condensation of 2-amino-4-chloro-6-hydroxy-s-triazine (2) with aminoacetaldehyde dimethyl acetal followed by the ring annulation gave the guanine analogue 8. A similar ring annulation of 4-(2,2-dimethoxyethylamino)-s-triazine-2,6-dione (5) gave imidazo[1,2-a]-s-triazine-4,6-dione (9). Direct glycosylation of the trimethylsilyl derivative of 8 with 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose in the presence of stannic chloride, followed by debenzoylation, gave the guanosine analogue 2-amino-8-(beta-D-ribofuranosyl)imidazo[1,2-a]-s-triazin-4-one (12b), which on deamination gave the xanthosine analogue 13. Phosphorylation of 12b gave 2-amino-8-(beta-D-ribofuranosyl)imidazo[1,2-a]-s-triazin-4-one 5'-monophosphate (II). The anomeric configuration has been determined unequivocally by using NMR of the 2',3'-O-isopropylidene derivate 10 and the site of ribosylation has been established by using 13C NMR spectroscopy. These compounds were tested against type 1 herpes, type 13 rhino, and type 3 parainfluenza viruses in tissue culture. Moderate rhinovirus activity was observed for several compounds at nontoxic dosage levels.", "contents": "Imidazo[1,2-a]-s-triazine nucleosides. Synthesis and antiviral activity of the N-bridgehead guanine, guanosine, and guanosine monophosphate analogues of imidazo[1,2-a]-s-triazine. The first chemical synthesis of 2-aminoimidazo[1,2-a]-s-triazin-4-one (8), the corresponding nucleoside and nucleotide, and certain related derivatives of a new class of purine analogues containing a bridgehead nitrogen atom is described. Condensation of 2-amino-4-chloro-6-hydroxy-s-triazine (2) with aminoacetaldehyde dimethyl acetal followed by the ring annulation gave the guanine analogue 8. A similar ring annulation of 4-(2,2-dimethoxyethylamino)-s-triazine-2,6-dione (5) gave imidazo[1,2-a]-s-triazine-4,6-dione (9). Direct glycosylation of the trimethylsilyl derivative of 8 with 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose in the presence of stannic chloride, followed by debenzoylation, gave the guanosine analogue 2-amino-8-(beta-D-ribofuranosyl)imidazo[1,2-a]-s-triazin-4-one (12b), which on deamination gave the xanthosine analogue 13. Phosphorylation of 12b gave 2-amino-8-(beta-D-ribofuranosyl)imidazo[1,2-a]-s-triazin-4-one 5'-monophosphate (II). The anomeric configuration has been determined unequivocally by using NMR of the 2',3'-O-isopropylidene derivate 10 and the site of ribosylation has been established by using 13C NMR spectroscopy. These compounds were tested against type 1 herpes, type 13 rhino, and type 3 parainfluenza viruses in tissue culture. Moderate rhinovirus activity was observed for several compounds at nontoxic dosage levels."}
{"id": "PMID:214564", "title": "Synthesis and prostaglandin-like activity of 2-(trans-3-hydroxy-1-octenyl)-3-indoleheptanoic acid.", "content": "The synthesis of 2-(trans-3-hydroxy-1-octenyl)-3-indoleheptanoic acid (1) is described. The title compound appeared to show a weak prostaglandin-like activity in two different systems. It contracted rat stomach fundus strips and guinea-pig ileum preparations only at concentrations about 10(3)- and 10(2)-fold higher, respectively, than PGE1. Moreover, it stimulated adenylate cyclase from rat liver plasma membrane, but the relative potency was 4--5 X 10(2)-fold lower than the natural compound. The title compound showed also a certain degree of PGE1 antagonism.", "contents": "Synthesis and prostaglandin-like activity of 2-(trans-3-hydroxy-1-octenyl)-3-indoleheptanoic acid. The synthesis of 2-(trans-3-hydroxy-1-octenyl)-3-indoleheptanoic acid (1) is described. The title compound appeared to show a weak prostaglandin-like activity in two different systems. It contracted rat stomach fundus strips and guinea-pig ileum preparations only at concentrations about 10(3)- and 10(2)-fold higher, respectively, than PGE1. Moreover, it stimulated adenylate cyclase from rat liver plasma membrane, but the relative potency was 4--5 X 10(2)-fold lower than the natural compound. The title compound showed also a certain degree of PGE1 antagonism."}
{"id": "PMID:214565", "title": "Jejunal microbial flora of southern indian infants in health and with acute gastroenteritis.", "content": "The microbial flora of the jejunal lumen of 28 infants with acute gastroenteritis was compared with that of a group of 10 normal infants. The jejunum of control subjects harboured an \"oral\" type of flora and in a few instances enterobacteria in small numbers. The concentrations of all but one of the groups of organism were higher in the patients than in controls, and the differences were of statistical significance for enterobacteria and lactobacilli. In eight subjects, the same pathogen was identified in the jejunum and the stool. In six subjects with rotavirus infection, there were almost no Gram-negative aerobic rods in the jejunum. The possible role of other Gram-negative aerobic rods in producing gastroenteritis is discussed. It is suggested that studies of jejunal flora are of considerable importance in assigning an aetiological role to bacteria in the causation of acute gastroenteritis.", "contents": "Jejunal microbial flora of southern indian infants in health and with acute gastroenteritis. The microbial flora of the jejunal lumen of 28 infants with acute gastroenteritis was compared with that of a group of 10 normal infants. The jejunum of control subjects harboured an \"oral\" type of flora and in a few instances enterobacteria in small numbers. The concentrations of all but one of the groups of organism were higher in the patients than in controls, and the differences were of statistical significance for enterobacteria and lactobacilli. In eight subjects, the same pathogen was identified in the jejunum and the stool. In six subjects with rotavirus infection, there were almost no Gram-negative aerobic rods in the jejunum. The possible role of other Gram-negative aerobic rods in producing gastroenteritis is discussed. It is suggested that studies of jejunal flora are of considerable importance in assigning an aetiological role to bacteria in the causation of acute gastroenteritis."}
{"id": "PMID:214570", "title": "Conditions leading to the establishment of the N (a gene dependent) and A (a gene independent) transformed states after polyoma virus infection of rat fibroblasts.", "content": "Infection of normal rat fibroblasts (FR 3T3) with the early tsa mutant of polyoma virus may lead to either the A or the N phenotype, tsa-A transformants, originally derived by agar selection, are not temperature dependent for maintenance of the transformed phenotype, whereas tsa-N transormants revert at high temperature to normal growth control. A transformants did not result from an independent cellular mutation selected in agar medium, but rather from a transformation process distinct from that leading to the N state. It occurred in both liquid and agar media when the infected cells were maintained under growth-restricting conditions, such as absence of anchorage and contact inhibition at confluency. N transformation occurred in cells maintained in active growth after virus infection (sparse cultures on a solid substratum). Physiological conditions during a critical period after virus infection thus appear to be a crucial parameter of the transformation process.", "contents": "Conditions leading to the establishment of the N (a gene dependent) and A (a gene independent) transformed states after polyoma virus infection of rat fibroblasts. Infection of normal rat fibroblasts (FR 3T3) with the early tsa mutant of polyoma virus may lead to either the A or the N phenotype, tsa-A transformants, originally derived by agar selection, are not temperature dependent for maintenance of the transformed phenotype, whereas tsa-N transormants revert at high temperature to normal growth control. A transformants did not result from an independent cellular mutation selected in agar medium, but rather from a transformation process distinct from that leading to the N state. It occurred in both liquid and agar media when the infected cells were maintained under growth-restricting conditions, such as absence of anchorage and contact inhibition at confluency. N transformation occurred in cells maintained in active growth after virus infection (sparse cultures on a solid substratum). Physiological conditions during a critical period after virus infection thus appear to be a crucial parameter of the transformation process."}
{"id": "PMID:214571", "title": "Detergent-inhibited, heat-labile nucleoside triphosphatase in cores of avian myeloblastosis virus.", "content": "Endogenous DNA synthesis was studied in isolated core particles of avian myeloblastosis virus. It was found that cores contained an enzymatic activity which rapidly converted the added nucleoside triphosphates to diphosphates (but not further) at 0 degrees C, thus inhibiting DNA synthesis. This triphosphatase probably originates from the viral membranes. In the cores the enzyme is completely inactivated by low concentrations (0.02%) of Nonident P-40. Also, the enzyme is very thermolabile and denatures rapidly at 38 degrees C.", "contents": "Detergent-inhibited, heat-labile nucleoside triphosphatase in cores of avian myeloblastosis virus. Endogenous DNA synthesis was studied in isolated core particles of avian myeloblastosis virus. It was found that cores contained an enzymatic activity which rapidly converted the added nucleoside triphosphates to diphosphates (but not further) at 0 degrees C, thus inhibiting DNA synthesis. This triphosphatase probably originates from the viral membranes. In the cores the enzyme is completely inactivated by low concentrations (0.02%) of Nonident P-40. Also, the enzyme is very thermolabile and denatures rapidly at 38 degrees C."}
{"id": "PMID:214572", "title": "Differential sensitivity of normal and transformed human cells to reovirus infection.", "content": "Normal and simian virus 40-transformed WI-38 cells exhibited a differential sensitivity to infection with type 3 reovirus. A progressive decrease in viability began 24 to 36 h after infection of transformed cells terminating in complete lysis of cultures by 96 h. Normal cells were productively infected and continued to produce and release virus for as long as 14 days after infection, but exhibited no detectable cytopathology. Inhibition of cellular DNA synthesis began 15 to 18 h after infection in transformed cells before development of cytopathology. No inhibition of DNA synthesis was detected in infected normal cells. No significant differences were noted in the adsorption or early replication characteristics of reovirus in normal and transformed cells. Virus replication and host cell DNA synthesis in normal and transformed human cells were compared to reovirus-infected L-929 mouse fibroblast cells.", "contents": "Differential sensitivity of normal and transformed human cells to reovirus infection. Normal and simian virus 40-transformed WI-38 cells exhibited a differential sensitivity to infection with type 3 reovirus. A progressive decrease in viability began 24 to 36 h after infection of transformed cells terminating in complete lysis of cultures by 96 h. Normal cells were productively infected and continued to produce and release virus for as long as 14 days after infection, but exhibited no detectable cytopathology. Inhibition of cellular DNA synthesis began 15 to 18 h after infection in transformed cells before development of cytopathology. No inhibition of DNA synthesis was detected in infected normal cells. No significant differences were noted in the adsorption or early replication characteristics of reovirus in normal and transformed cells. Virus replication and host cell DNA synthesis in normal and transformed human cells were compared to reovirus-infected L-929 mouse fibroblast cells."}
{"id": "PMID:214573", "title": "Autoregulation of adenovirus type 5 early gene expression II. Effect of temperature-sensitive early mutations on virus RNA accumulation.", "content": "The kinetics of accumulation of early virus RNA in the cytoplasm of KB cells infected at 40.5 degrees C by wild-type (WT) adenovirus type 5 and a temperature-sensitive \"early\" mutant, H5ts125 (ts125), were compared by hybridization of unlabeled RNA in solution to the (3)H-labeled l strand of Ad5 DNA HindIII restriction endonuclease fragment A. In the presence of 1-beta-d-arabinofuranosylcytosine, A(l) RNA accumulated in WT-infected cells for 9 h and then decreased in concentration to 6% of the 9-h concentration by 18 h. In ts125-infected cells, A(l) RNA accumulated for 12 h and then remained at the same concentration for at least 6 h thereafter. The concentrations of virus RNA from the four early transcription regions of the genome were measured at 15 h in cells infected at 40.5 degrees C in the presence of 1-beta-d-arabinofuranosylcytosine by: (i) ts125 and WT; (ii) two other ts early mutants, ts107 and ts149; and (iii) a revertant of ts125. The revertant and ts149, a mutant from a different complementation group than ts125, both accumulated all early virus cytoplasmic RNA species in amounts similar to, or less than, WT. However, both ts125 and ts107, independently isolated mutations in the 72,000-molecular-weight (72K) DNA-binding protein gene, accumulated cytoplasmic early RNA in excess of that found in WT infection. This pattern of RNA accumulation with the mutants and WT virus was the same in the nuclei as in the cytoplasm at 40.5 degrees C. At 32 degrees C, however, the abundance of nuclear virus RNA from all four early regions was the same in cells infected by either ts125 or WT. Differences in the relative abundance of nuclear RNA from the four early regions were observed in cells infected at 40.5 and 32 degrees C, but were not dependent upon the infecting virus genotype. These results are consistent with autoregulation of early gene expression by the 72K protein and support the hypothesis that the 72K protein either decreases the rate of early virus transcription or increases the rate of virus RNA degradation in the nucleus.", "contents": "Autoregulation of adenovirus type 5 early gene expression II. Effect of temperature-sensitive early mutations on virus RNA accumulation. The kinetics of accumulation of early virus RNA in the cytoplasm of KB cells infected at 40.5 degrees C by wild-type (WT) adenovirus type 5 and a temperature-sensitive \"early\" mutant, H5ts125 (ts125), were compared by hybridization of unlabeled RNA in solution to the (3)H-labeled l strand of Ad5 DNA HindIII restriction endonuclease fragment A. In the presence of 1-beta-d-arabinofuranosylcytosine, A(l) RNA accumulated in WT-infected cells for 9 h and then decreased in concentration to 6% of the 9-h concentration by 18 h. In ts125-infected cells, A(l) RNA accumulated for 12 h and then remained at the same concentration for at least 6 h thereafter. The concentrations of virus RNA from the four early transcription regions of the genome were measured at 15 h in cells infected at 40.5 degrees C in the presence of 1-beta-d-arabinofuranosylcytosine by: (i) ts125 and WT; (ii) two other ts early mutants, ts107 and ts149; and (iii) a revertant of ts125. The revertant and ts149, a mutant from a different complementation group than ts125, both accumulated all early virus cytoplasmic RNA species in amounts similar to, or less than, WT. However, both ts125 and ts107, independently isolated mutations in the 72,000-molecular-weight (72K) DNA-binding protein gene, accumulated cytoplasmic early RNA in excess of that found in WT infection. This pattern of RNA accumulation with the mutants and WT virus was the same in the nuclei as in the cytoplasm at 40.5 degrees C. At 32 degrees C, however, the abundance of nuclear virus RNA from all four early regions was the same in cells infected by either ts125 or WT. Differences in the relative abundance of nuclear RNA from the four early regions were observed in cells infected at 40.5 and 32 degrees C, but were not dependent upon the infecting virus genotype. These results are consistent with autoregulation of early gene expression by the 72K protein and support the hypothesis that the 72K protein either decreases the rate of early virus transcription or increases the rate of virus RNA degradation in the nucleus."}
{"id": "PMID:214574", "title": "Does simian virus 40 DNA integrate into cellular DNA during productive infection?", "content": "Late after infection of permissive monkey cells by simian virus 40 (SV40), large amounts of SV40 DNA (30,000 to 220,000 viral genome equivalents per cell) can be isolated with the high-molecular-weight fraction of cellular DNA. Hirai and Defendi (J. Virol.9:705-707, 1972) and H\u00f6lzel and Sokol (J. Mol. Biol. 84:423-444, 1974) suggested that this SV40 DNA is covalently integrated into the cellular DNA. However, our data indicate that the high-molecular-weight viral DNA is  composed of tandem, \"head-to-tail\" repeats of SV40 DNA and that very little, if any, of this viral DNA is covalently joined to the cellular DNA. This was deduced from the following experimental findings. The size of the SV40 DNA associated with the high-molecular-weight cellular DNA fraction is greater than 45 kilobases, based on its electrophoretic mobility in agarose gels. In this form the SV40 DNA did not produce heteroduplex structures with a marker viral DNA (an SV40 genome with a characteristic deletion and duplication). After the high-molecular-weight DNA was digested with EcoRI or HpaII endonucleases, enzymes which cleave SV40 DNA once, more than 95% of the SV40 DNA migrated as unit-length linear molecules and, after hybridization with the marker viral DNA, the expected heteroduplex structures were easily detected. Digestion of the high-molecular-weight DNA fraction with restriction endonucleases that cleave cellular, but not SV40. DNA did not alter the electrophoretic mobility of the polymeric SV40 DNA, nor did it give rise to molecules that form heteroduplex structures with the marker viral DNA. Polymeric SV40 DNA molecules produced after coinfection by two physically distinguishable SV40 genomes contain only a single type of genome, suggesting that they arise by replication rather than by recombination. The polymeric form of SV40 DNA is highly infectious for CV-1P monolayers (6.5 X 10(4) PFU per  microgram of SV40 DNA), yielding virtually exclusively normal, covalently closed circular, monomer-length DNA. Quite clearly these cells have an efficient mechanism for generating monomeric viral DNA from the SV40 DNA polymers.", "contents": "Does simian virus 40 DNA integrate into cellular DNA during productive infection? Late after infection of permissive monkey cells by simian virus 40 (SV40), large amounts of SV40 DNA (30,000 to 220,000 viral genome equivalents per cell) can be isolated with the high-molecular-weight fraction of cellular DNA. Hirai and Defendi (J. Virol.9:705-707, 1972) and H\u00f6lzel and Sokol (J. Mol. Biol. 84:423-444, 1974) suggested that this SV40 DNA is covalently integrated into the cellular DNA. However, our data indicate that the high-molecular-weight viral DNA is  composed of tandem, \"head-to-tail\" repeats of SV40 DNA and that very little, if any, of this viral DNA is covalently joined to the cellular DNA. This was deduced from the following experimental findings. The size of the SV40 DNA associated with the high-molecular-weight cellular DNA fraction is greater than 45 kilobases, based on its electrophoretic mobility in agarose gels. In this form the SV40 DNA did not produce heteroduplex structures with a marker viral DNA (an SV40 genome with a characteristic deletion and duplication). After the high-molecular-weight DNA was digested with EcoRI or HpaII endonucleases, enzymes which cleave SV40 DNA once, more than 95% of the SV40 DNA migrated as unit-length linear molecules and, after hybridization with the marker viral DNA, the expected heteroduplex structures were easily detected. Digestion of the high-molecular-weight DNA fraction with restriction endonucleases that cleave cellular, but not SV40. DNA did not alter the electrophoretic mobility of the polymeric SV40 DNA, nor did it give rise to molecules that form heteroduplex structures with the marker viral DNA. Polymeric SV40 DNA molecules produced after coinfection by two physically distinguishable SV40 genomes contain only a single type of genome, suggesting that they arise by replication rather than by recombination. The polymeric form of SV40 DNA is highly infectious for CV-1P monolayers (6.5 X 10(4) PFU per  microgram of SV40 DNA), yielding virtually exclusively normal, covalently closed circular, monomer-length DNA. Quite clearly these cells have an efficient mechanism for generating monomeric viral DNA from the SV40 DNA polymers."}
{"id": "PMID:214575", "title": "Recombinants between herpes simplex virus types 1 and 2: analyses of genome structures and expression of immediate early polypeptides.", "content": "Recombinants between temperature-sensitive mutants of herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) were constructed. Using restriction endonucleases, we analyzed the genome composition of 17 intertypic recombinants and detected crossovers in every region of the genome. The virion DNA of one recombinant appeared to be largely \"frozen\" in two of the four possible genome arrangements of HSV. Knowledge of the genome structures of recombinants enabled us to physically map immediate early polypeptides. We present evidence that the immediate early polypeptide Vmw IE 110 of HSV-1 and its functionally equivalent polypeptide, Vmw IE 118, of HSV-2 may map in the repetitive sequences bounding the long unique region of HSV.", "contents": "Recombinants between herpes simplex virus types 1 and 2: analyses of genome structures and expression of immediate early polypeptides. Recombinants between temperature-sensitive mutants of herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) were constructed. Using restriction endonucleases, we analyzed the genome composition of 17 intertypic recombinants and detected crossovers in every region of the genome. The virion DNA of one recombinant appeared to be largely \"frozen\" in two of the four possible genome arrangements of HSV. Knowledge of the genome structures of recombinants enabled us to physically map immediate early polypeptides. We present evidence that the immediate early polypeptide Vmw IE 110 of HSV-1 and its functionally equivalent polypeptide, Vmw IE 118, of HSV-2 may map in the repetitive sequences bounding the long unique region of HSV."}
{"id": "PMID:214576", "title": "DNA of Epstein-Barr virus. IV. Linkage map of restriction enzyme fragments of the B95-8 and W91 strains of Epstein-Barr Virus.", "content": "The arrangement of EcoRI, Hsu I, and Sal I restriction enzyme sites in the DNA of the B95-8 and W91 isolates of Epstein-Barr virus (EBV) has been determined from the size of the single-enzyme-cleaved fragments and from blot hybridizations that identify which fragments cut from the DNA with one enzyme contain nucleotide sequences in common with fragments cut from the DNA with a second enzyme. The DNA of the B95-8 isolate was the prototype for this study. The data indicate that  (i) approximately 95 X 10(6) to 100 X 10(6) daltons of EBV (B95-8) DNA is in a consistent and unique sequence arrangement. (ii) Both termini are variable in length. One end of the molecule after Hsu I endonuclease cleavage consists of approximately 3,000 base pairs, with as many as 10 additional 500-base pair segments. The opposite end of the molecule after Sal I endonuclease cleavage consists of approximately 1,500 base pairs, with as many as 10 additional 500-base pair segments. (iii) The opposite ends of the molecule contain homologous sequences. The high degree of homology between the opposite ends of the molecule and the similarity in size of the \"additional\" 500-base pair segments suggests that there are identical repeating units at both ends of the DNA. The arrangement of restriction endonuclease fragments of the DNA of the W91 isolate of EBV is similar to that of the B95-8 isolate and differs from the latter in the presence of approximately 7 X 10(6) daltons of \"extra\" DNA at a single site. Thus, the size of almost all EcoRI, Hsu I, and Sal I fragments of EBV (W91) DNA is identical to that of fragments of EBV (B95-8) DNA. A single EcoRI fragment, C, of EBV (W91) DNA is approximately 7 X 10(6) daltons larger than the corresponding EcoRI fragment of EBV (B95-8) DNA. Digestion of EBV (W91) DNA with Hsu I or Sal I restriction endonucleases produces two fragments (Hsu I D1 and D2 or Sal I G2 and G3) which differ in total size by approximately 7 X 10(6) daltons from the fragments of EBV (B95-8) DNA. Furthermore, the EcoRI, Hsu I, and Sal I fragments of EBV (W91) and (B95-8) DNAs, which are of similar molecular weight, have homologous nucleotide sequences. Moreover, the W91 fragments contain only sequences from a single region of the B95-8 genome. Two lines of evidence indicate that the \"extra\" sequences present in W91 EcoRI fragment C are viral DNA and not cellular. (i) The molecular weight of the \"enlarged\" EcoRI C fragment of EBV (W91) DNA is identical to that of the EcoRI C fragment of another isolate of EBV (Jijoye), (ii) The HR-1 clone of Jijoye has previously been shown to contain DNA which is not present in the B95-8 strain but is present in the EcoRI C and Hsu I D2 and D1 fragments of EBV (W91) DNA (N. Raab-Traub, R. Pritchett, and E. Kieff, J. Virol. 27:388-398, 1978).", "contents": "DNA of Epstein-Barr virus. IV. Linkage map of restriction enzyme fragments of the B95-8 and W91 strains of Epstein-Barr Virus. The arrangement of EcoRI, Hsu I, and Sal I restriction enzyme sites in the DNA of the B95-8 and W91 isolates of Epstein-Barr virus (EBV) has been determined from the size of the single-enzyme-cleaved fragments and from blot hybridizations that identify which fragments cut from the DNA with one enzyme contain nucleotide sequences in common with fragments cut from the DNA with a second enzyme. The DNA of the B95-8 isolate was the prototype for this study. The data indicate that  (i) approximately 95 X 10(6) to 100 X 10(6) daltons of EBV (B95-8) DNA is in a consistent and unique sequence arrangement. (ii) Both termini are variable in length. One end of the molecule after Hsu I endonuclease cleavage consists of approximately 3,000 base pairs, with as many as 10 additional 500-base pair segments. The opposite end of the molecule after Sal I endonuclease cleavage consists of approximately 1,500 base pairs, with as many as 10 additional 500-base pair segments. (iii) The opposite ends of the molecule contain homologous sequences. The high degree of homology between the opposite ends of the molecule and the similarity in size of the \"additional\" 500-base pair segments suggests that there are identical repeating units at both ends of the DNA. The arrangement of restriction endonuclease fragments of the DNA of the W91 isolate of EBV is similar to that of the B95-8 isolate and differs from the latter in the presence of approximately 7 X 10(6) daltons of \"extra\" DNA at a single site. Thus, the size of almost all EcoRI, Hsu I, and Sal I fragments of EBV (W91) DNA is identical to that of fragments of EBV (B95-8) DNA. A single EcoRI fragment, C, of EBV (W91) DNA is approximately 7 X 10(6) daltons larger than the corresponding EcoRI fragment of EBV (B95-8) DNA. Digestion of EBV (W91) DNA with Hsu I or Sal I restriction endonucleases produces two fragments (Hsu I D1 and D2 or Sal I G2 and G3) which differ in total size by approximately 7 X 10(6) daltons from the fragments of EBV (B95-8) DNA. Furthermore, the EcoRI, Hsu I, and Sal I fragments of EBV (W91) and (B95-8) DNAs, which are of similar molecular weight, have homologous nucleotide sequences. Moreover, the W91 fragments contain only sequences from a single region of the B95-8 genome. Two lines of evidence indicate that the \"extra\" sequences present in W91 EcoRI fragment C are viral DNA and not cellular. (i) The molecular weight of the \"enlarged\" EcoRI C fragment of EBV (W91) DNA is identical to that of the EcoRI C fragment of another isolate of EBV (Jijoye), (ii) The HR-1 clone of Jijoye has previously been shown to contain DNA which is not present in the B95-8 strain but is present in the EcoRI C and Hsu I D2 and D1 fragments of EBV (W91) DNA (N. Raab-Traub, R. Pritchett, and E. Kieff, J. Virol. 27:388-398, 1978)."}
{"id": "PMID:214577", "title": "Absence of circularly permuted and largely redundant sequences in the genome of visna virus.", "content": "A previous study of the infectivity of visna virus proviral DNA suggested that the genetic information of the virus is distributed over at least two of the RNA subunits. Because the genetic complexity of visna virus corresponds to the size of one subunit, this result may imply that sequence redundancies exist within each subunit. In the present article we have examined this question by constructing a map of the large RNase T1-resistant oligonucleotides of the viral genome. Our principal results are as follows: (i) all 36S RNA subunits have the same genetic content regardless of their polyadenylic acid [poly(A)] content; (ii) the poly(A) tract is present at the 3' end of the molecule; and (iii) the recoveries of 19 large RNase T1-resistant oligonucleotides from poly(A)-tagged RNA fragments of various sizes demonstrate that the oligonucleotides are organized in the same linear order within all subunits. Our results, therefore, exclude the existence of large sequence redundancies in the genome of visna virus.", "contents": "Absence of circularly permuted and largely redundant sequences in the genome of visna virus. A previous study of the infectivity of visna virus proviral DNA suggested that the genetic information of the virus is distributed over at least two of the RNA subunits. Because the genetic complexity of visna virus corresponds to the size of one subunit, this result may imply that sequence redundancies exist within each subunit. In the present article we have examined this question by constructing a map of the large RNase T1-resistant oligonucleotides of the viral genome. Our principal results are as follows: (i) all 36S RNA subunits have the same genetic content regardless of their polyadenylic acid [poly(A)] content; (ii) the poly(A) tract is present at the 3' end of the molecule; and (iii) the recoveries of 19 large RNase T1-resistant oligonucleotides from poly(A)-tagged RNA fragments of various sizes demonstrate that the oligonucleotides are organized in the same linear order within all subunits. Our results, therefore, exclude the existence of large sequence redundancies in the genome of visna virus."}
{"id": "PMID:214578", "title": "Characterization of Rous sarcoma virus src gene products synthesized in vitro.", "content": "The cell-free synthesis of three major proteins from virion RNA of nondefective Rous sarcoma virus (RSV), but not from RNA of transformation-defective deletion mutants, has been observed. The apparent molecular weights of these transformation-specific proteins are approximately 60,000 (60K), 25K, and 17K. Tryptic maps of methionine-containing peptides revealed the 17K, 25K, and 60K proteins to be overlapping in sequence. However, only partial homology was observed between the 17K, 25K and 60K proteins synthesized from Schmidt-Ruppin strain, subgroup D, RSV RNA and those synthesized from Prague strain, subgroup B, RSV, RNA. About half of the methionine peptides in the Schmidt-Ruppin strain, subgroup D, 60K protein were shared with the Prague strain, subgroup D, 60K protein, and the rest were distinct to each. The virion RNAs coding for the 60K, 25K, and 17K proteins were found to be polyadenylated and to sediment with maximal mRNA activity at about 23, 19 to 20, and 18S, respectively. In addition, transformation-specific proteins with molecular weights of 39K and 33K were observed by in vitro synthesis. These proteins are also related to the 60K, 25K, and 17K proteins and were synthesized from polyadenylated RSV RNA of approximately 21 to 22S. RNase T1-resistant oligonucleotides were analyzed in parallel, and the src-specific oligonucleotides were found to be first present in equimolar amounts in those gradient fractions sedimenting at 21 to 22S. Our data suggest that synthesis of the 60K protein is initiated near the 5' terminus of the src gene, whereas the 39K, 33K, 25K, and 17K proteins are initiated internally in the src gene. All of these proteins appear to be initiated independently, but they may have a common termination site.", "contents": "Characterization of Rous sarcoma virus src gene products synthesized in vitro. The cell-free synthesis of three major proteins from virion RNA of nondefective Rous sarcoma virus (RSV), but not from RNA of transformation-defective deletion mutants, has been observed. The apparent molecular weights of these transformation-specific proteins are approximately 60,000 (60K), 25K, and 17K. Tryptic maps of methionine-containing peptides revealed the 17K, 25K, and 60K proteins to be overlapping in sequence. However, only partial homology was observed between the 17K, 25K and 60K proteins synthesized from Schmidt-Ruppin strain, subgroup D, RSV RNA and those synthesized from Prague strain, subgroup B, RSV, RNA. About half of the methionine peptides in the Schmidt-Ruppin strain, subgroup D, 60K protein were shared with the Prague strain, subgroup D, 60K protein, and the rest were distinct to each. The virion RNAs coding for the 60K, 25K, and 17K proteins were found to be polyadenylated and to sediment with maximal mRNA activity at about 23, 19 to 20, and 18S, respectively. In addition, transformation-specific proteins with molecular weights of 39K and 33K were observed by in vitro synthesis. These proteins are also related to the 60K, 25K, and 17K proteins and were synthesized from polyadenylated RSV RNA of approximately 21 to 22S. RNase T1-resistant oligonucleotides were analyzed in parallel, and the src-specific oligonucleotides were found to be first present in equimolar amounts in those gradient fractions sedimenting at 21 to 22S. Our data suggest that synthesis of the 60K protein is initiated near the 5' terminus of the src gene, whereas the 39K, 33K, 25K, and 17K proteins are initiated internally in the src gene. All of these proteins appear to be initiated independently, but they may have a common termination site."}
{"id": "PMID:214579", "title": "Ends of the RNA within Sendai virus defective interfering nucleocapsids are not free.", "content": "Sendai virus defective interfering nucleocapsids, isolated from infected cell cytoplasm by equilibrium banding in CsCl gradients, contain only the viral N protein. Neither end of the genomic RNA within these nucleocapsids is accessible to RNase digestion.", "contents": "Ends of the RNA within Sendai virus defective interfering nucleocapsids are not free. Sendai virus defective interfering nucleocapsids, isolated from infected cell cytoplasm by equilibrium banding in CsCl gradients, contain only the viral N protein. Neither end of the genomic RNA within these nucleocapsids is accessible to RNase digestion."}
{"id": "PMID:214580", "title": "Selective degradation of newly synthesized nonmessenger simian virus 40 transcripts.", "content": "By pretreating simian virus 40-infected BSC-1 cells with glucosamine, [(3)H]uridine labeling of both cellular and viral RNA can be halted instantaneously by addition of cold uridine. We have studied the fate of pulse-labeled viral RNA from cells at 45 h postinfection under these conditions. During a 5-min period of labeling, both the messenger and nonmessenger regions of the late strand were transcribed. After various chase periods, nuclear viral species which sediment at 19, 17.5, and 16S were observed. Nuclear viral RNA decays in a multiphasic manner. Of the material present at the beginning of the chase period, 50% was degraded rapidly with a half-life of 8 min (initial processing). This rapidly degraded material was that fraction of the late strand which did not give rise to stable late mRNA species. Forty percent was transported to the cytoplasm, and 10% remained in the nucleus as material which sedimented in the 2 to 4S region. These 2 to 4S viral RNAs had a half-life of 3 h, and hybridization studies suggest that they are in part coded for by the late-strand nonmessenger region and are derived from the initial nuclear processing step. Another part is coded for by the late-strand messenger region and may be generated by some subsequent nuclear cleavages of 19S RNA into 17.5 and 16S RNAs. Transport of nuclear viral RNA into the cytoplasm was detected after a 5-min pulse and a 7-min chase. The maximum amount of labeled viral RNA was accumulated in the cytoplasm after a 30-min to 1-h chase. At least two viral cytoplasmic species were observed. Kinetic data suggest that 19S RNA is transported directly from the nucleus. Whether cytoplasmic 16S is formed by cleavage of 19S RNA in the cytoplasm is not clear. The half-lives of cytoplasmic 19 and 16S RNAs can be approximated as 2 and 5 h, respectively.", "contents": "Selective degradation of newly synthesized nonmessenger simian virus 40 transcripts. By pretreating simian virus 40-infected BSC-1 cells with glucosamine, [(3)H]uridine labeling of both cellular and viral RNA can be halted instantaneously by addition of cold uridine. We have studied the fate of pulse-labeled viral RNA from cells at 45 h postinfection under these conditions. During a 5-min period of labeling, both the messenger and nonmessenger regions of the late strand were transcribed. After various chase periods, nuclear viral species which sediment at 19, 17.5, and 16S were observed. Nuclear viral RNA decays in a multiphasic manner. Of the material present at the beginning of the chase period, 50% was degraded rapidly with a half-life of 8 min (initial processing). This rapidly degraded material was that fraction of the late strand which did not give rise to stable late mRNA species. Forty percent was transported to the cytoplasm, and 10% remained in the nucleus as material which sedimented in the 2 to 4S region. These 2 to 4S viral RNAs had a half-life of 3 h, and hybridization studies suggest that they are in part coded for by the late-strand nonmessenger region and are derived from the initial nuclear processing step. Another part is coded for by the late-strand messenger region and may be generated by some subsequent nuclear cleavages of 19S RNA into 17.5 and 16S RNAs. Transport of nuclear viral RNA into the cytoplasm was detected after a 5-min pulse and a 7-min chase. The maximum amount of labeled viral RNA was accumulated in the cytoplasm after a 30-min to 1-h chase. At least two viral cytoplasmic species were observed. Kinetic data suggest that 19S RNA is transported directly from the nucleus. Whether cytoplasmic 16S is formed by cleavage of 19S RNA in the cytoplasm is not clear. The half-lives of cytoplasmic 19 and 16S RNAs can be approximated as 2 and 5 h, respectively."}
{"id": "PMID:214581", "title": "Identification of nucleotide sequences which may encode the oncogenic capacity of avian retrovirus MC29.", "content": "The retrovirus strain MC29 induces a variety of tumors in chickens, including myelocytomatosis and carcinomas of the kidney and liver. In addition, the virus can transform cultures of embryonic avian macrophages and fibroblasts. We have characterized the genome of MC29 virus and have identified nucleotide sequences that may encode the oncogenic potential ofthe virus. MC29 virus can replicate only with the assistance of a related helper virus. The defect in replication is apparently a consequence of a deletion in one or more viral genes: the haploid genome of the MC29 virus has a molecular weight of ca. 1.7 X 10(6), whereas the genome of the helper virus MCAV has a molecular weight of ca. 3.1 X 10(6). Although MC29 virus transforms fibroblasts in culture, its genome has no detectable homology with the gene src that is responsible for transformation of fibroblasts by avian sarcoma viruses. We prepared radioactive single-stranded DNA complementary to nucleotide sequences present in the genome of MC29 virus but not in the genome of MCAV (cDNA(MC29)). If they are contiguous, these sequences (ca. 1,500 nucleotides) are sufficiently complex to encode at least one protein. Homologous sequences were not detectable in several strains of avian sarcoma viruses or in an endogenous virus of chickens. Our findings confirm and extend recent reports from other laboratories and lead to the conclusion that MC29 virus may contain a previously unidentified gene(s) that is capable of transforming several distinct target cells. The evolutionary origins of this putative gene and its location on the viral genome can be explored with cDNA(MC29).", "contents": "Identification of nucleotide sequences which may encode the oncogenic capacity of avian retrovirus MC29. The retrovirus strain MC29 induces a variety of tumors in chickens, including myelocytomatosis and carcinomas of the kidney and liver. In addition, the virus can transform cultures of embryonic avian macrophages and fibroblasts. We have characterized the genome of MC29 virus and have identified nucleotide sequences that may encode the oncogenic potential ofthe virus. MC29 virus can replicate only with the assistance of a related helper virus. The defect in replication is apparently a consequence of a deletion in one or more viral genes: the haploid genome of the MC29 virus has a molecular weight of ca. 1.7 X 10(6), whereas the genome of the helper virus MCAV has a molecular weight of ca. 3.1 X 10(6). Although MC29 virus transforms fibroblasts in culture, its genome has no detectable homology with the gene src that is responsible for transformation of fibroblasts by avian sarcoma viruses. We prepared radioactive single-stranded DNA complementary to nucleotide sequences present in the genome of MC29 virus but not in the genome of MCAV (cDNA(MC29)). If they are contiguous, these sequences (ca. 1,500 nucleotides) are sufficiently complex to encode at least one protein. Homologous sequences were not detectable in several strains of avian sarcoma viruses or in an endogenous virus of chickens. Our findings confirm and extend recent reports from other laboratories and lead to the conclusion that MC29 virus may contain a previously unidentified gene(s) that is capable of transforming several distinct target cells. The evolutionary origins of this putative gene and its location on the viral genome can be explored with cDNA(MC29)."}
{"id": "PMID:214582", "title": "Modulation of mouse mammary tumor virus production in the MJY-alpha cell line.", "content": "Implantation of the mouse mammary tumor virus (MMTV)-producing mammary tumor cell line MJY-alpha into isogeneic mice elicited both humoral and T-cell responses against MMTV virion antigens. The carcinosarcomas which developed from the implanted cells showed a significant decrease in MMTV synthesis, compared with cells remaining in culture, which was detectable as early as 7 days after implantation and for five transplant generations. Electron microscopic examination of thin sections of the tumors revealed that intracytoplasmic A particles, budding particles, and cell-free MMTV B particles were all affected. However, immunofluorescence assays of tumor sections demonstrated the presence of MMTV viral antigens in the cells. Cell cultures initiated from first-, third-, and fourth-generation tumors were morphologically identical to the original in vitro cell line, although virus production was barely detectable. Analysis of the cultures by electron microscopy revealed a significant increase in MMTV virions after in vitro passage 3. Polypeptide profiles obtained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of virions purified from these cultures were identical to MMTV. Immunodiffusion demonstrated the cross-reactivity between these virions and MMTV particles obtained from mouse milk. In vitro treatment of MJY-alpha cell cultures with rabbit anti-MMTV antiserum resulted in a reduction of extracellular MMTV virions, as well as alterations in their sodium dodecyl sulfate-polyacrylamide gel electrophoretic polypeptide patterns.", "contents": "Modulation of mouse mammary tumor virus production in the MJY-alpha cell line. Implantation of the mouse mammary tumor virus (MMTV)-producing mammary tumor cell line MJY-alpha into isogeneic mice elicited both humoral and T-cell responses against MMTV virion antigens. The carcinosarcomas which developed from the implanted cells showed a significant decrease in MMTV synthesis, compared with cells remaining in culture, which was detectable as early as 7 days after implantation and for five transplant generations. Electron microscopic examination of thin sections of the tumors revealed that intracytoplasmic A particles, budding particles, and cell-free MMTV B particles were all affected. However, immunofluorescence assays of tumor sections demonstrated the presence of MMTV viral antigens in the cells. Cell cultures initiated from first-, third-, and fourth-generation tumors were morphologically identical to the original in vitro cell line, although virus production was barely detectable. Analysis of the cultures by electron microscopy revealed a significant increase in MMTV virions after in vitro passage 3. Polypeptide profiles obtained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of virions purified from these cultures were identical to MMTV. Immunodiffusion demonstrated the cross-reactivity between these virions and MMTV particles obtained from mouse milk. In vitro treatment of MJY-alpha cell cultures with rabbit anti-MMTV antiserum resulted in a reduction of extracellular MMTV virions, as well as alterations in their sodium dodecyl sulfate-polyacrylamide gel electrophoretic polypeptide patterns."}
{"id": "PMID:214583", "title": "Physical mapping of herpes simplex virus-induced polypeptides.", "content": "Analysis of the polypeptides induced by 29 herpes simplex virus type 1/type 2 intertypic recombinants and correlation of the data with the crossover points in the recombinant DNAs have enabled the map positions of many polypeptides to be deduced. These include 25 polypeptides which label with [35S]methionine, 11 which label with [32P]orthophosphate, and 4 which label with [14C]glucosamine. Together with the data of Preston et al. (J. Virol., in press) on the mapping of five immediate-early polypeptides, the results show that representatives of four groups of proteins--immediate-early, late, phosphorylated, and glycosylated--map in both long and short regions. The functional organization of the herpes simplex virus genome does not therefore restrict any of these four groups to either the long or the short region.", "contents": "Physical mapping of herpes simplex virus-induced polypeptides. Analysis of the polypeptides induced by 29 herpes simplex virus type 1/type 2 intertypic recombinants and correlation of the data with the crossover points in the recombinant DNAs have enabled the map positions of many polypeptides to be deduced. These include 25 polypeptides which label with [35S]methionine, 11 which label with [32P]orthophosphate, and 4 which label with [14C]glucosamine. Together with the data of Preston et al. (J. Virol., in press) on the mapping of five immediate-early polypeptides, the results show that representatives of four groups of proteins--immediate-early, late, phosphorylated, and glycosylated--map in both long and short regions. The functional organization of the herpes simplex virus genome does not therefore restrict any of these four groups to either the long or the short region."}
{"id": "PMID:214584", "title": "Replication-defective ecotropic murine leukemia viruses: Detection and quantitation of infectivity using helper-dependent XC plaque formation.", "content": "Clones 8A and NP-N, which appear to be infected with replication-defective variants of murine leukemia virus, produce particles which do not form plques in the XC test. These particles formed XC plaques when amphotropic murine leukemia virus, which is XC negative, was added to the assay plates. This phenomenon can be used as a quantitiative infectivity assay for these replication-defective murine leukemia viruses.", "contents": "Replication-defective ecotropic murine leukemia viruses: Detection and quantitation of infectivity using helper-dependent XC plaque formation. Clones 8A and NP-N, which appear to be infected with replication-defective variants of murine leukemia virus, produce particles which do not form plques in the XC test. These particles formed XC plaques when amphotropic murine leukemia virus, which is XC negative, was added to the assay plates. This phenomenon can be used as a quantitiative infectivity assay for these replication-defective murine leukemia viruses."}
{"id": "PMID:214585", "title": "Chromatin pattern consisting of repeating bipartite structures in WI-38 cells infected with human cytomegalovirus.", "content": "A novel chromatin structural pattern displaying bipartite and oblate ellipsoid structures orderly arranged along a fiber axis has been observed in WI-38 cells infected with human cytomegalovirus. This chromatin type coexists with chromatin fibers showing conventional nucleosomes. Each bipartite-oblate structure is 40 nm in length, about four times as long as an ordinary nucleosome, and the number of these structures per micrometer (11/micrometer) is clearly less than that of typical cellular nucleosomes (32/micrometer).", "contents": "Chromatin pattern consisting of repeating bipartite structures in WI-38 cells infected with human cytomegalovirus. A novel chromatin structural pattern displaying bipartite and oblate ellipsoid structures orderly arranged along a fiber axis has been observed in WI-38 cells infected with human cytomegalovirus. This chromatin type coexists with chromatin fibers showing conventional nucleosomes. Each bipartite-oblate structure is 40 nm in length, about four times as long as an ordinary nucleosome, and the number of these structures per micrometer (11/micrometer) is clearly less than that of typical cellular nucleosomes (32/micrometer)."}
{"id": "PMID:214586", "title": "Translation of type C viral RNAs in Xenopus laevis oocytes: evidence that the 120,000-molecular-weight polyprotein expressed in Abelson leukemia virus-transformed cells is virus coded.", "content": "The genomic RNA of Abelson leukemia virus (AbLV) has been purified and translated in Xenopus laevis oocytes. The primary AbLV-specific protein synthesized is a polyprotein corresponding in molecular weight and immunological properties to a previously described p15 and p12 containing 110,000- to 130,000-molecular-weight polyprotein expressed in AbLV-transformed cells. In contrast, translation of woolly monkey sarcoma virus genomic RNA resulted in symthesis of a 55,000-molecular-weight polyprotein consisting of woolly helper virus p30, p15, and p12. These findings demonstrate the value of the X. laevis oocyte in vitro system for studies of translational products of replication-defective transforming viruses and establish the virus-coded nature of the nonstructural component of the 110,000- to 130,000-molecular-weight polyprotein expressed in AbLV-transformed cells.", "contents": "Translation of type C viral RNAs in Xenopus laevis oocytes: evidence that the 120,000-molecular-weight polyprotein expressed in Abelson leukemia virus-transformed cells is virus coded. The genomic RNA of Abelson leukemia virus (AbLV) has been purified and translated in Xenopus laevis oocytes. The primary AbLV-specific protein synthesized is a polyprotein corresponding in molecular weight and immunological properties to a previously described p15 and p12 containing 110,000- to 130,000-molecular-weight polyprotein expressed in AbLV-transformed cells. In contrast, translation of woolly monkey sarcoma virus genomic RNA resulted in symthesis of a 55,000-molecular-weight polyprotein consisting of woolly helper virus p30, p15, and p12. These findings demonstrate the value of the X. laevis oocyte in vitro system for studies of translational products of replication-defective transforming viruses and establish the virus-coded nature of the nonstructural component of the 110,000- to 130,000-molecular-weight polyprotein expressed in AbLV-transformed cells."}
{"id": "PMID:214588", "title": "Parainfluenza type 3 in a transplant unit.", "content": "We observed an epidemic of parainfluenza type 3 viral infection in a renal transplantation service among 16 recent transplant recipients. To assess the effect of infection on transplant function, we retrospectively compared the infected patients with a matched, uninfected control group. In addition to symptoms of a mild upper respiratory tract infection associated with the epidemic, there was an increase in the frequency of acute rejection episodes during the period of infection in the infected group. Nevertheless, outcome in terms of patient and graft survival at six months was not affected when compared with the survival rates of the control group.", "contents": "Parainfluenza type 3 in a transplant unit. We observed an epidemic of parainfluenza type 3 viral infection in a renal transplantation service among 16 recent transplant recipients. To assess the effect of infection on transplant function, we retrospectively compared the infected patients with a matched, uninfected control group. In addition to symptoms of a mild upper respiratory tract infection associated with the epidemic, there was an increase in the frequency of acute rejection episodes during the period of infection in the infected group. Nevertheless, outcome in terms of patient and graft survival at six months was not affected when compared with the survival rates of the control group."}
{"id": "PMID:214589", "title": "Herpes simplex virus type I from a patient with radiculoneuropathy.", "content": "Herpes simplex virus type I was isolated from the CSF of a patient with atypical lumbosacral pain. The features of this case are unusual and important in light of the current understanding of herpes-simplex-virus-associated neurologic disease.", "contents": "Herpes simplex virus type I from a patient with radiculoneuropathy. Herpes simplex virus type I was isolated from the CSF of a patient with atypical lumbosacral pain. The features of this case are unusual and important in light of the current understanding of herpes-simplex-virus-associated neurologic disease."}
{"id": "PMID:214599", "title": "Effects of cadmium ion on the Na,K-ATPase of microsomes obtained from frog skin.", "content": "We have developed a new simple procedure for separating the epidermis from the dermis of the bullfrog (Rana catesbeiana) (freezing and scraping off the skin), and extracting microsomal fraction from the epidermis. The effects of Cd on the ATPase activity of the microsomal fraction was investigated by varying Na and/or K concentrations in the reaction medium. The higher the concentration of Cd, the larger the decreases were found in both activities of ouabain-sensitive ATPase and ouabain-insensitive ATPase in the range of Cd concentration from 10(-7) M to 10(-3) M. The activity of ouabain-sensitive ATPase (Na, K-ATPase) was completely inhibited by 1 mM Cd. The amount of Cd uptake into the whole skin was about 150 micrometer/kg wet weight. This concentration of Cd was sufficient to inhibit the Na, K-ATPase activity of the microsomes. The mechanisms underlying the three types of Cd effects on the frog skin were discussed in relation to the Na, K-ATPase activity.", "contents": "Effects of cadmium ion on the Na,K-ATPase of microsomes obtained from frog skin. We have developed a new simple procedure for separating the epidermis from the dermis of the bullfrog (Rana catesbeiana) (freezing and scraping off the skin), and extracting microsomal fraction from the epidermis. The effects of Cd on the ATPase activity of the microsomal fraction was investigated by varying Na and/or K concentrations in the reaction medium. The higher the concentration of Cd, the larger the decreases were found in both activities of ouabain-sensitive ATPase and ouabain-insensitive ATPase in the range of Cd concentration from 10(-7) M to 10(-3) M. The activity of ouabain-sensitive ATPase (Na, K-ATPase) was completely inhibited by 1 mM Cd. The amount of Cd uptake into the whole skin was about 150 micrometer/kg wet weight. This concentration of Cd was sufficient to inhibit the Na, K-ATPase activity of the microsomes. The mechanisms underlying the three types of Cd effects on the frog skin were discussed in relation to the Na, K-ATPase activity."}
{"id": "PMID:214600", "title": "Differential effects of D 600 on release of catecholamines by acetylcholine, histamine, tyramine and by cyclic AMP from canine adrenal medulla.", "content": "The isolated canine adrenal glands were perfused retrogradely with Locke's solution, and the catecholamine contents of the effluents were measured by the trihydroxyindole-fluorimetric method. Stimulation of the glands by acetylcholine, histamine, tyramine and cyclic AMP caused an increase in release of catecholamines from the glands. Introduction of D 600 of the perfusion medium reduced release of catecholamines in response to acetylcholine, and this reduction was overcome by raising calcium ion concentrations of the perfusion medium. Similarly, D 600 reduced release of catecholamines in response to histamine. The release of catecholamines evoked by tyramine was also inhibited by D 600, although to a lesser degree than the release by acetylcholine. In contrast, D 600 was entirely ineffective on the catecholamine release in response to cyclic AMP. D 600 had no effect on the spontaneous catecholamine output. From these results it was concluded that release of catecholamines from adrenal chromaffin cells by acetylcholine and histamine, and by tyramine in part requires the entry of calcium ions across the cell membane, whereas that by cyclic AMP does not.", "contents": "Differential effects of D 600 on release of catecholamines by acetylcholine, histamine, tyramine and by cyclic AMP from canine adrenal medulla. The isolated canine adrenal glands were perfused retrogradely with Locke's solution, and the catecholamine contents of the effluents were measured by the trihydroxyindole-fluorimetric method. Stimulation of the glands by acetylcholine, histamine, tyramine and cyclic AMP caused an increase in release of catecholamines from the glands. Introduction of D 600 of the perfusion medium reduced release of catecholamines in response to acetylcholine, and this reduction was overcome by raising calcium ion concentrations of the perfusion medium. Similarly, D 600 reduced release of catecholamines in response to histamine. The release of catecholamines evoked by tyramine was also inhibited by D 600, although to a lesser degree than the release by acetylcholine. In contrast, D 600 was entirely ineffective on the catecholamine release in response to cyclic AMP. D 600 had no effect on the spontaneous catecholamine output. From these results it was concluded that release of catecholamines from adrenal chromaffin cells by acetylcholine and histamine, and by tyramine in part requires the entry of calcium ions across the cell membane, whereas that by cyclic AMP does not."}
{"id": "PMID:214606", "title": "Enhanced plating efficiency of herpesvirus DNA on herpes simplex virus type 1 DNA-transformed cells.", "content": "Partial resistance of hamster cells transformed by sheared herpes simplex virus (HSV) DNA to superinfection by intact HSV could be overcome by transfection with viral DNA's. HSV DNA plated more efficiently on HSV type 1 DNA-transformed hamster cells than on spontaneously transformed hamster or rabbit cells or on hamster cells transformed by other DNA viruses.", "contents": "Enhanced plating efficiency of herpesvirus DNA on herpes simplex virus type 1 DNA-transformed cells. Partial resistance of hamster cells transformed by sheared herpes simplex virus (HSV) DNA to superinfection by intact HSV could be overcome by transfection with viral DNA's. HSV DNA plated more efficiently on HSV type 1 DNA-transformed hamster cells than on spontaneously transformed hamster or rabbit cells or on hamster cells transformed by other DNA viruses."}
{"id": "PMID:214610", "title": "Congenital transmission of murine leukemia virus from wild mice prone to the development of lymphoma and paralysis.", "content": "Maternal congenital transmission of infectious murine leukemia virus, primarily via milk, was the major route of virus spread in Lake Casitas (LC) wild mice and in crosses of LC mice with uninfected wild and laboratory mice. An indirect extrachromosomal male transmission in utero of LC virus also readily occurred in matings of viremic LC males with C57L females but apparently not with other uninfected wild or NIH Swiss females. Both amphotropic and ecotropic classes of LC murine leukemia viruses were potentially transmissible by congenital and venereal epigenetic means and could induce the same two diseases, lymphoma and paralysis, that occurred naturally in LC wild mice. Lymphoma and paralysis both failed to occur in uninfected LC mice or their hybrid progeny that escaped congenital infection.", "contents": "Congenital transmission of murine leukemia virus from wild mice prone to the development of lymphoma and paralysis. Maternal congenital transmission of infectious murine leukemia virus, primarily via milk, was the major route of virus spread in Lake Casitas (LC) wild mice and in crosses of LC mice with uninfected wild and laboratory mice. An indirect extrachromosomal male transmission in utero of LC virus also readily occurred in matings of viremic LC males with C57L females but apparently not with other uninfected wild or NIH Swiss females. Both amphotropic and ecotropic classes of LC murine leukemia viruses were potentially transmissible by congenital and venereal epigenetic means and could induce the same two diseases, lymphoma and paralysis, that occurred naturally in LC wild mice. Lymphoma and paralysis both failed to occur in uninfected LC mice or their hybrid progeny that escaped congenital infection."}
{"id": "PMID:214611", "title": "A rapid neutralization test for antibodies to bovine leukemia virus, with the use of rhabdovirus pseudotypes.", "content": "Two rhabdoviruses, vesicular stomatitis (type Indiana) and Chandipura viruses, formed pseudotype particles with envelope antigens provided by bovine leukemia virus (BLV). The pseudotypes are infectious for calf, human, mink, and rat cells, but the most sensitive indicator proved to be the Vero cells. Infectivity of the pseudotypes was increased by DEAE-dextran present during adsorption. Sera of spontaneously infected cattle contained high titers (some over 1/10,000) of antibodies neutralizing the pseudotypes, whereas sera of cattle from uninfected herds possessed no neutralizing activity in 1/10 dilution. The neutralization of these pseudotypes can serve as a rapid and sensitive test for the detection of antibodies in the cattle infected with BLV.", "contents": "A rapid neutralization test for antibodies to bovine leukemia virus, with the use of rhabdovirus pseudotypes. Two rhabdoviruses, vesicular stomatitis (type Indiana) and Chandipura viruses, formed pseudotype particles with envelope antigens provided by bovine leukemia virus (BLV). The pseudotypes are infectious for calf, human, mink, and rat cells, but the most sensitive indicator proved to be the Vero cells. Infectivity of the pseudotypes was increased by DEAE-dextran present during adsorption. Sera of spontaneously infected cattle contained high titers (some over 1/10,000) of antibodies neutralizing the pseudotypes, whereas sera of cattle from uninfected herds possessed no neutralizing activity in 1/10 dilution. The neutralization of these pseudotypes can serve as a rapid and sensitive test for the detection of antibodies in the cattle infected with BLV."}
{"id": "PMID:214612", "title": "Venereal herpes: a nursing overview.", "content": "Nursing problems associated with venereal herpes are examined. Clinical manifestations, as well as specific effects on the pregnant woman, fetus, and neonate, are discussed. Additional discussion focuses on prevention and therapy and the relation of venereal herpes to cervical cancer. A list of nursing implications is appended; it includes assessment and intervention, patient teaching, nursing education, and public policy.", "contents": "Venereal herpes: a nursing overview. Nursing problems associated with venereal herpes are examined. Clinical manifestations, as well as specific effects on the pregnant woman, fetus, and neonate, are discussed. Additional discussion focuses on prevention and therapy and the relation of venereal herpes to cervical cancer. A list of nursing implications is appended; it includes assessment and intervention, patient teaching, nursing education, and public policy."}
{"id": "PMID:214619", "title": "[Cyclic nucleotides in the blood plasma in arterial hypertension].", "content": "The reaction of cyclic nucleotides in blood to an orthostatic position, furosemid administration, and submaximal bicycle ergometry load was studied in 20 healthy individuals and in 50 patients with hypertensive disease. A special group was composed of 25 patients the disease in whom was marked by crises. It is shown that a walk of one hour and intravenous infusion of 40 mg of furosemid caused an increase in the blood cAMP but did not change the level of cGMP. During a bicycle ergometry load the levels of cGMP and cGMP increased to an equal measure and returned to their initial values 30 min after its cessation. In patients with arterial hypertension the cGMP system becomes most functionally mobile, whereas the cAMP level, if it increases, does so at a later term after the effect of the stimulus begins. The increased cGMP level is maintained for quite a lengthy period of time after the load is discontinued. In patients suffering from hypertensive disease with crises the cAMP/cGMP ratio, which is reduced at rest also, diminishes still more in an orthostatic position and particularly during a crisis. The role of changes in the metabolism of cyclic nucleotides and their sensitivity to regulatory factors in the pathogenesis of arterial hypertension is discussed.", "contents": "[Cyclic nucleotides in the blood plasma in arterial hypertension]. The reaction of cyclic nucleotides in blood to an orthostatic position, furosemid administration, and submaximal bicycle ergometry load was studied in 20 healthy individuals and in 50 patients with hypertensive disease. A special group was composed of 25 patients the disease in whom was marked by crises. It is shown that a walk of one hour and intravenous infusion of 40 mg of furosemid caused an increase in the blood cAMP but did not change the level of cGMP. During a bicycle ergometry load the levels of cGMP and cGMP increased to an equal measure and returned to their initial values 30 min after its cessation. In patients with arterial hypertension the cGMP system becomes most functionally mobile, whereas the cAMP level, if it increases, does so at a later term after the effect of the stimulus begins. The increased cGMP level is maintained for quite a lengthy period of time after the load is discontinued. In patients suffering from hypertensive disease with crises the cAMP/cGMP ratio, which is reduced at rest also, diminishes still more in an orthostatic position and particularly during a crisis. The role of changes in the metabolism of cyclic nucleotides and their sensitivity to regulatory factors in the pathogenesis of arterial hypertension is discussed."}
{"id": "PMID:214624", "title": "[The judgement of collagen metabolism by hydroxyproline in plasma and urine and plasma collagenic peptidase under different diet (author's transl)].", "content": "In 34 subjects--coal workers with pneumoconiosis, patients with collagenic diseases and healthy subjects--the daily urinary excretion of hydroxyproline (HP) and the plasma concentrations of HP and of collagenic peptidase have been measured during one week under HP-free and HP-enriched diet. It is shown that a 24-hour period of HP-free diet is necessary and sufficient before collecting urine or plasma for diet independent measurements of total or non-protein bound HP. Concentrations in plasma correlate well with the amounts excreted in urine. Collagenic peptidase is independent from the diet and well suited for assessment of the activity of the metabolism of collagene. There are no differences between healthy subjects and coal workers with pneumoconiosis.", "contents": "[The judgement of collagen metabolism by hydroxyproline in plasma and urine and plasma collagenic peptidase under different diet (author's transl)]. In 34 subjects--coal workers with pneumoconiosis, patients with collagenic diseases and healthy subjects--the daily urinary excretion of hydroxyproline (HP) and the plasma concentrations of HP and of collagenic peptidase have been measured during one week under HP-free and HP-enriched diet. It is shown that a 24-hour period of HP-free diet is necessary and sufficient before collecting urine or plasma for diet independent measurements of total or non-protein bound HP. Concentrations in plasma correlate well with the amounts excreted in urine. Collagenic peptidase is independent from the diet and well suited for assessment of the activity of the metabolism of collagene. There are no differences between healthy subjects and coal workers with pneumoconiosis."}
{"id": "PMID:214635", "title": "Enterotoxemia in rabbits.", "content": "The presence of Clostridium perfringens Type E iota toxin was confirmed from the cecal contents of 23 of 46 rabbits which died of enteritis complex. The most consistent lesions observed were hemorrhage and edema in the cecum. Rabbit toxicity tests showed the toxic cecal contents were lethal for young rabbits unless incubated with Clostridium perfringens Type E antiserum.", "contents": "Enterotoxemia in rabbits. The presence of Clostridium perfringens Type E iota toxin was confirmed from the cecal contents of 23 of 46 rabbits which died of enteritis complex. The most consistent lesions observed were hemorrhage and edema in the cecum. Rabbit toxicity tests showed the toxic cecal contents were lethal for young rabbits unless incubated with Clostridium perfringens Type E antiserum."}
{"id": "PMID:214636", "title": "A fatal enteric syndrome in Mystromys albicaudatus (white tailed rat) following topical antibiotic treatment.", "content": "Heavy death losses (59%) occurred in adult Mystromys 3--14 days after muscle biopsies were taken from their rear legs. Clinical signs included anorexia, depression, and rough hair coat. Predominant necropsy findings were hrmorrhagic typhlitis and colitis. Results of studies evaluating the roles of the anesthetic and the tropical antibiotic ointment suggested that the deaths were caused by ingestion of the topically applied antibiotic.", "contents": "A fatal enteric syndrome in Mystromys albicaudatus (white tailed rat) following topical antibiotic treatment. Heavy death losses (59%) occurred in adult Mystromys 3--14 days after muscle biopsies were taken from their rear legs. Clinical signs included anorexia, depression, and rough hair coat. Predominant necropsy findings were hrmorrhagic typhlitis and colitis. Results of studies evaluating the roles of the anesthetic and the tropical antibiotic ointment suggested that the deaths were caused by ingestion of the topically applied antibiotic."}
{"id": "PMID:214639", "title": "Inhibition of the binding of low-density lipoprotein to its cell surface receptor in human fibroblasts by positively charged proteins.", "content": "A group of proteins and polyamino acids with positively charged domains were shown to inhibit the binding of 125I-LDL to its receptor on the surface of human fibroblasts. The list of inhibitory proteins included platelet factor 4 (which has a cluster of lysine residues at its carboxyl terminus), two lysine-rich histones, poly-L-lysines of chain length greater than 4, and protamine. These proteins were effective in the concentration range of 5--10 microgram/ml. Two other positively charged proteins, lysozyme and avidin, did not inhibit 125I-LDL binding. Kinetic studies suggested that protamine was not acting simply as a competitive inhibitor with regard to the LDL receptor. In light of previous data showing that polyanions such as heparin and polyphosphates also inhibit 125-I-LDL binding to its cell surface receptor, the current findings suggest that charge interactions are important in this binding reaction. In a related series of studies, a number of glycoproteins and their asialo derivatives as well as a number of sugar phosphates failed to inhibit 125I-LDL binding to its receptor in fibroblasts.", "contents": "Inhibition of the binding of low-density lipoprotein to its cell surface receptor in human fibroblasts by positively charged proteins. A group of proteins and polyamino acids with positively charged domains were shown to inhibit the binding of 125I-LDL to its receptor on the surface of human fibroblasts. The list of inhibitory proteins included platelet factor 4 (which has a cluster of lysine residues at its carboxyl terminus), two lysine-rich histones, poly-L-lysines of chain length greater than 4, and protamine. These proteins were effective in the concentration range of 5--10 microgram/ml. Two other positively charged proteins, lysozyme and avidin, did not inhibit 125I-LDL binding. Kinetic studies suggested that protamine was not acting simply as a competitive inhibitor with regard to the LDL receptor. In light of previous data showing that polyanions such as heparin and polyphosphates also inhibit 125-I-LDL binding to its cell surface receptor, the current findings suggest that charge interactions are important in this binding reaction. In a related series of studies, a number of glycoproteins and their asialo derivatives as well as a number of sugar phosphates failed to inhibit 125I-LDL binding to its receptor in fibroblasts."}
{"id": "PMID:214640", "title": "The program of Friend cell erythroid differentiation: early changes in Na+/K+ ATPase function.", "content": "Treatment of Friend erythroleukemia cells with several different chemical agents causes an early decrease in the 86Rb+ influx mediated by Na+/K+ adenosine triphosphatase (ATPase). These agents, which induce Friend cells to differentiate, include dimethylsulfoxide (DMSO), ouabain, hypoxanthine, and actinomycin D. The magnitude of the early decrease in 86Rb+ influx correlates with the proportion of cells in cultures of inducible Friend cell clones which later go on to synthesize hemoglobin. Compounds which do not incude differentiation in these cells, such as xanthine, exogenous hematin, and erythropoietin, do not cause a change in 86Rb+ influx. A change in the intracellular K+ ion concentration does not occur during induction by DMSO because, although there is a decrease in K+ content per cell soon after induction, there is a parallel decrease in cell volume. These results and previous observations from this laboratory are discussed in terms of the posible involvement of the Na+/K+ ATPase in Friend cell differentiation.", "contents": "The program of Friend cell erythroid differentiation: early changes in Na+/K+ ATPase function. Treatment of Friend erythroleukemia cells with several different chemical agents causes an early decrease in the 86Rb+ influx mediated by Na+/K+ adenosine triphosphatase (ATPase). These agents, which induce Friend cells to differentiate, include dimethylsulfoxide (DMSO), ouabain, hypoxanthine, and actinomycin D. The magnitude of the early decrease in 86Rb+ influx correlates with the proportion of cells in cultures of inducible Friend cell clones which later go on to synthesize hemoglobin. Compounds which do not incude differentiation in these cells, such as xanthine, exogenous hematin, and erythropoietin, do not cause a change in 86Rb+ influx. A change in the intracellular K+ ion concentration does not occur during induction by DMSO because, although there is a decrease in K+ content per cell soon after induction, there is a parallel decrease in cell volume. These results and previous observations from this laboratory are discussed in terms of the posible involvement of the Na+/K+ ATPase in Friend cell differentiation."}
{"id": "PMID:214641", "title": "Mechanism of action of choleragen.", "content": "Choleragen exerts its effect on cells through activation of adenylate cyclase. Choleragen initially interacts with cells through binding of the B subunit of the toxin to the ganglioside GM1 on the cell surface. Subsequent events are less clear. Patching or capping of toxin on the cell surface may be an obligatory step in choleragen action. Studies in cell-free systems have demonstrated that activation of adenylate cyclase by choleragen requires NAD. In addition to NAD, requirements have been observed for ATP, GTP, and calcium-dependent regulatory protein. GTP also is required for the expression of choleragen-activated adenylate cyclase. In preparations from turkey erythrocytes, choleragen appears to inhibit an isoproterenol-stimulated GTPase. It has been postulated that by decreasing the activity of a specific GTPase, choleragen would stabilize a GTP-adenylate cyclase complex and maintain the cyclase in an activated state. Although the holotoxin is most effective in intact cells, with the A subunit having 1/20th of its activity and the B subunit (choleragenoid) being inactive, in cell-free systems the A subunit, specifically the A1 fragment, is required for adenylate cyclase activation. The B protomer is inactive. Choleragen, the A subunit, or A1 fragment under suitable conditions hydrolyzes NAD to ADP-ribose and nicotinamide (NAD glycohydrolase activity) and catalyzes the transfer of the ADP-ribose moiety of NAD to the guandino group of arginine (ADP-ribosyltransferase activity). The NAD glycohydrolase activity is similar to that exhibited by other NAD-dependent bacterial toxins (diphtheria toxin, Pseudomonas exotoxin A), which act by catalyzing the ADP-ribosylation of a specific acceptor protein. If the ADP-ribosylation of arginine is a model for the reaction catalyzed by choleragen in vivo, then arginine is presumably an analog of the amino acid which is ADP-ribosylated in the acceptor protein. It is postulated that choleragen exerts its effects on cells through the NAD-dependent ADP-ribosylation of an arginine or similar amino acid in either the cyclase itself or a regulatory protein of the cyclase system.", "contents": "Mechanism of action of choleragen. Choleragen exerts its effect on cells through activation of adenylate cyclase. Choleragen initially interacts with cells through binding of the B subunit of the toxin to the ganglioside GM1 on the cell surface. Subsequent events are less clear. Patching or capping of toxin on the cell surface may be an obligatory step in choleragen action. Studies in cell-free systems have demonstrated that activation of adenylate cyclase by choleragen requires NAD. In addition to NAD, requirements have been observed for ATP, GTP, and calcium-dependent regulatory protein. GTP also is required for the expression of choleragen-activated adenylate cyclase. In preparations from turkey erythrocytes, choleragen appears to inhibit an isoproterenol-stimulated GTPase. It has been postulated that by decreasing the activity of a specific GTPase, choleragen would stabilize a GTP-adenylate cyclase complex and maintain the cyclase in an activated state. Although the holotoxin is most effective in intact cells, with the A subunit having 1/20th of its activity and the B subunit (choleragenoid) being inactive, in cell-free systems the A subunit, specifically the A1 fragment, is required for adenylate cyclase activation. The B protomer is inactive. Choleragen, the A subunit, or A1 fragment under suitable conditions hydrolyzes NAD to ADP-ribose and nicotinamide (NAD glycohydrolase activity) and catalyzes the transfer of the ADP-ribose moiety of NAD to the guandino group of arginine (ADP-ribosyltransferase activity). The NAD glycohydrolase activity is similar to that exhibited by other NAD-dependent bacterial toxins (diphtheria toxin, Pseudomonas exotoxin A), which act by catalyzing the ADP-ribosylation of a specific acceptor protein. If the ADP-ribosylation of arginine is a model for the reaction catalyzed by choleragen in vivo, then arginine is presumably an analog of the amino acid which is ADP-ribosylated in the acceptor protein. It is postulated that choleragen exerts its effects on cells through the NAD-dependent ADP-ribosylation of an arginine or similar amino acid in either the cyclase itself or a regulatory protein of the cyclase system."}
{"id": "PMID:214643", "title": "[Sudden deafness and cytomegalievirusinfection of adults (author's transl)].", "content": "By means of virologuc--serologic examination methods it was possible to find in four patients with sudden deafness a cytomegaloinfection, whereby the complement-fixation reaction was determined with the CMV antigen. With the usual therapeutical measures all cases with an, in part high-degree, labyrinthine deafness improved or normalized simultaneously with the serologically ascertained subsiding of the virus infection. The paper discusses the pathogenesis of viruscaused sudden deafness and tries to explain the benign nature of central complications in cytomegaloinfections.", "contents": "[Sudden deafness and cytomegalievirusinfection of adults (author's transl)]. By means of virologuc--serologic examination methods it was possible to find in four patients with sudden deafness a cytomegaloinfection, whereby the complement-fixation reaction was determined with the CMV antigen. With the usual therapeutical measures all cases with an, in part high-degree, labyrinthine deafness improved or normalized simultaneously with the serologically ascertained subsiding of the virus infection. The paper discusses the pathogenesis of viruscaused sudden deafness and tries to explain the benign nature of central complications in cytomegaloinfections."}
{"id": "PMID:214644", "title": "[Giant cell tumor of tendon sheath in association with synovialchondroma. An unusual tumor-combination at the temporomandibular joint (author's transl)].", "content": "A tumor at the temporomandibular joint is reported, which so far has not yet been described. Histologically it turned out to be a combination of synovialchondroma and giant cell tumor of tendon sheath. By reason of the microscopic picture and the course of 2 1/2 years without relapse it is a benign tumor. In postoperative x-rays of the mandible a thickening and sclerosis as well as cystic areas of increased translucence at the place of removal of the tumor were found, which had already existed preoperatively in a lower degree.", "contents": "[Giant cell tumor of tendon sheath in association with synovialchondroma. An unusual tumor-combination at the temporomandibular joint (author's transl)]. A tumor at the temporomandibular joint is reported, which so far has not yet been described. Histologically it turned out to be a combination of synovialchondroma and giant cell tumor of tendon sheath. By reason of the microscopic picture and the course of 2 1/2 years without relapse it is a benign tumor. In postoperative x-rays of the mandible a thickening and sclerosis as well as cystic areas of increased translucence at the place of removal of the tumor were found, which had already existed preoperatively in a lower degree."}
{"id": "PMID:214645", "title": "[Myxoma of the mastoid with destruction of the facial nerve (author's transl)].", "content": "A case of Myxoma of the mastoid with initial facial spasme followed by palsy of the nerve is reported. After removing the tumor the nerve has been reconstructed from the secound knee until the stylomastoid foramen. The probable origine of the tumor is discussed.", "contents": "[Myxoma of the mastoid with destruction of the facial nerve (author's transl)]. A case of Myxoma of the mastoid with initial facial spasme followed by palsy of the nerve is reported. After removing the tumor the nerve has been reconstructed from the secound knee until the stylomastoid foramen. The probable origine of the tumor is discussed."}
{"id": "PMID:214660", "title": "Differences in the phospholipid, cholesterol, and fatty acyl composition of 3T3 and SV3T3 plasma membranes.", "content": "An analysis of the phospholipid, cholesterol, and phospholipid fatty acyl composition of isolated plasma membranes of 3T3 and SV3T3 mouse mebryo cells has been performed. The results show that the plasma membrane of SV3T3 cells contain relatively less phosphatidylethanolamine and sphingomyelin and more cholesterol than 3T3 plasma membranes. The fatty acyl composition of individual phospholipid classes as determined by gas liquid chromatography also showed differences between 3T3 and SV3T3 plasma membranes. The plasma membranes of SV40 transformed 3T3 cells contain: (a) a higher percentage of 18:1 and less 20:3 and 20:4 in phosphatidylethanolamine; (b) a higher percentage of 18:1 in phosphatidylserine; and (c) a higher percentage of 18:2 and 20:4 in phosphatidylinositol.", "contents": "Differences in the phospholipid, cholesterol, and fatty acyl composition of 3T3 and SV3T3 plasma membranes. An analysis of the phospholipid, cholesterol, and phospholipid fatty acyl composition of isolated plasma membranes of 3T3 and SV3T3 mouse mebryo cells has been performed. The results show that the plasma membrane of SV3T3 cells contain relatively less phosphatidylethanolamine and sphingomyelin and more cholesterol than 3T3 plasma membranes. The fatty acyl composition of individual phospholipid classes as determined by gas liquid chromatography also showed differences between 3T3 and SV3T3 plasma membranes. The plasma membranes of SV40 transformed 3T3 cells contain: (a) a higher percentage of 18:1 and less 20:3 and 20:4 in phosphatidylethanolamine; (b) a higher percentage of 18:1 in phosphatidylserine; and (c) a higher percentage of 18:2 and 20:4 in phosphatidylinositol."}
{"id": "PMID:214666", "title": "[Experimental silicosis. II. Fibrogenic effect of natural amorphous silica].", "content": "Fibrogenic effect of two natural amorphous silica dusts-diatomite from deposits near Leszczawka (Poland) and silica earth (from the USA) was tested on the rats. Pneumoconiosis was produced by intratracheal introduction of 50 mg dust, at a single dose. Fibrogenic effect was assessed after 3, 6 and 9 months after introduction of dust. Analysis of diatomite dust carried out with X-ray diffraction method showed the presence of quartz in a quantity not exceeding 5%, while in silica earth dust from the USA no silica critalline structures were found. Development of fibrogenic changes in lungs of the rats assessed with hydroxyproline (collagen) increase and weight increment of wet lungs was small. The increment of the indices was twice higher as compared with their increment found in the lungs of control animals but lower than in the rats which were given cristalline silica dusts. In histopathological examinations no progressive lung fibrosis was found though some signs of destruction and necrobiosis in some cells were noticed.", "contents": "[Experimental silicosis. II. Fibrogenic effect of natural amorphous silica]. Fibrogenic effect of two natural amorphous silica dusts-diatomite from deposits near Leszczawka (Poland) and silica earth (from the USA) was tested on the rats. Pneumoconiosis was produced by intratracheal introduction of 50 mg dust, at a single dose. Fibrogenic effect was assessed after 3, 6 and 9 months after introduction of dust. Analysis of diatomite dust carried out with X-ray diffraction method showed the presence of quartz in a quantity not exceeding 5%, while in silica earth dust from the USA no silica critalline structures were found. Development of fibrogenic changes in lungs of the rats assessed with hydroxyproline (collagen) increase and weight increment of wet lungs was small. The increment of the indices was twice higher as compared with their increment found in the lungs of control animals but lower than in the rats which were given cristalline silica dusts. In histopathological examinations no progressive lung fibrosis was found though some signs of destruction and necrobiosis in some cells were noticed."}
{"id": "PMID:214663", "title": "[Treatment of African vesico-vaginal fistulae in a rural hospital (author's transl)].", "content": "The author reports his own experience of this difficult surgery in a rural african hospital. He describes various types of fistulae and 3 technics which gave him 10 recoveries in 19 patients. Complications, rules of treatment and nursing are considered.", "contents": "[Treatment of African vesico-vaginal fistulae in a rural hospital (author's transl)]. The author reports his own experience of this difficult surgery in a rural african hospital. He describes various types of fistulae and 3 technics which gave him 10 recoveries in 19 patients. Complications, rules of treatment and nursing are considered."}
{"id": "PMID:214667", "title": "Bioassay of TSH using dog thyroid cells in monolayer culture.", "content": "The cAMP response to TSH stimulation in dog thyroid cells in monolayer culture was adapted as a means to assay TSH bioactivity. Of a variety of polypeptide hormones examined, only TSH and LH stimulated thyroid cell cAMP generation, but stimulation by LH probably represented contamination with TSH. Serum was found to be a potent, noncompetitive inhibitor of the thyroid cell cAMP response to TSH stimulation. The inhibitor(s) present in serum was nondialyzable and, on Sephadex G-200 gel filtration, eluted over a wide range between the void volume and the albumin peak. Because of this inhibitory effect of serum, partial purification of TSH from serum was necessary, and was achieved using Sephacryl S-200 gel filtration. Columns were calibrated with human TSH as measured by radioimmunoassay and bovine TSH as measured by bioassay. Intraassay variation of the thyroid cell cAMP response to a 100 microU/ml TSH standard was 9.2%. TSH standards were added to human serum following which the TSH was extracted by gel filtration and assayed for bioactivity. With TSH standards of 100 microU/ml intra-assay variation was 19.9%; and with TSH standards of 25 microU/ml, interassay variation was 34.5%. TSH bioactivity was demonstrable in serum from 21 of 25 patients with primary hypothyroidism, 4 of 14 normal subjects and none of 3 patients on exogenous thyroxine replacement. Although a positive correlation was observed between serum TSH bioactivity and immunoactivity, numerous individual samples displayed a dichotomy between the two measurements. This study provides new evidence that immunoassayable TSH in the serum of patients with primary hypothyroidism is not necessarily synonymous with TSH bioactivity.", "contents": "Bioassay of TSH using dog thyroid cells in monolayer culture. The cAMP response to TSH stimulation in dog thyroid cells in monolayer culture was adapted as a means to assay TSH bioactivity. Of a variety of polypeptide hormones examined, only TSH and LH stimulated thyroid cell cAMP generation, but stimulation by LH probably represented contamination with TSH. Serum was found to be a potent, noncompetitive inhibitor of the thyroid cell cAMP response to TSH stimulation. The inhibitor(s) present in serum was nondialyzable and, on Sephadex G-200 gel filtration, eluted over a wide range between the void volume and the albumin peak. Because of this inhibitory effect of serum, partial purification of TSH from serum was necessary, and was achieved using Sephacryl S-200 gel filtration. Columns were calibrated with human TSH as measured by radioimmunoassay and bovine TSH as measured by bioassay. Intraassay variation of the thyroid cell cAMP response to a 100 microU/ml TSH standard was 9.2%. TSH standards were added to human serum following which the TSH was extracted by gel filtration and assayed for bioactivity. With TSH standards of 100 microU/ml intra-assay variation was 19.9%; and with TSH standards of 25 microU/ml, interassay variation was 34.5%. TSH bioactivity was demonstrable in serum from 21 of 25 patients with primary hypothyroidism, 4 of 14 normal subjects and none of 3 patients on exogenous thyroxine replacement. Although a positive correlation was observed between serum TSH bioactivity and immunoactivity, numerous individual samples displayed a dichotomy between the two measurements. This study provides new evidence that immunoassayable TSH in the serum of patients with primary hypothyroidism is not necessarily synonymous with TSH bioactivity."}
{"id": "PMID:214664", "title": "[Children death rates in a rural village of Ivory Coast (author's transl)].", "content": "A 10 years statistical study with a global death rate of 63 per 1.0000 and its changes according to the age groups.", "contents": "[Children death rates in a rural village of Ivory Coast (author's transl)]. A 10 years statistical study with a global death rate of 63 per 1.0000 and its changes according to the age groups."}
{"id": "PMID:214668", "title": "The role of free fatty acids in the regulation of lipolysis by human adipose tissue cells.", "content": "The effect of added fatty acid on lipolysis and cyclic AMP concentration of human adipose tissue cells was studied. The addition of sodium oleate decreased the lipolytic response of adipocytes to 10(-7) M isoproterenol. Inhibition was detectable with the lowest quantity of oleate added, 0.2 mM, and was progressively greater with increasing quantities of added fatty acid. Palmitic and linoleic acids were as effective as oleic acid in suppressing isoproterenol-stimulated lipolysis. Suppression of cyclic AMP formation was detectable within one minute after the addition of oleate. Cyclic AMP formation, suppressed by accumulated fatty acids, could not be stimulated by the addition of fresh isoproterenol. However, after the accumulated fatty acids were removed by buffer change, cyclic AMP formation was stimulated by fresh isoproterenol. These findings are consistent with the view that fatty acids are physiologically significant regulators of lipolysis.", "contents": "The role of free fatty acids in the regulation of lipolysis by human adipose tissue cells. The effect of added fatty acid on lipolysis and cyclic AMP concentration of human adipose tissue cells was studied. The addition of sodium oleate decreased the lipolytic response of adipocytes to 10(-7) M isoproterenol. Inhibition was detectable with the lowest quantity of oleate added, 0.2 mM, and was progressively greater with increasing quantities of added fatty acid. Palmitic and linoleic acids were as effective as oleic acid in suppressing isoproterenol-stimulated lipolysis. Suppression of cyclic AMP formation was detectable within one minute after the addition of oleate. Cyclic AMP formation, suppressed by accumulated fatty acids, could not be stimulated by the addition of fresh isoproterenol. However, after the accumulated fatty acids were removed by buffer change, cyclic AMP formation was stimulated by fresh isoproterenol. These findings are consistent with the view that fatty acids are physiologically significant regulators of lipolysis."}
{"id": "PMID:214669", "title": "Electron microscopic studies of tumor viruses. II. Entry and uncoating of Epstein-Barr virus.", "content": "Entry of Epstein-Barr virus into human lymphoblastoid cells (Daudi cells) was studied by electron microscopy. At the site of viral attachment, two distinct interactions conducive to penetration of the virus occurred between the viral envelope and cell membrane, namely, (i) simultaneous dissolution of both the envelope and cell membrane, presumably resulting in passage of viral capsids into the cytoplasm and (ii) dissolution confined to the cell membrane with resulting penetration of enveloped virus. In the latter case envelope dissolution appears to occur subsequently in the cytoplasm with release of capsids. Fusion of the viral envelope with the cell membrane was not observed. The capsids exhibited two distinct structural forms--one dense, the other translucent or light in appearance. The former disrupted near the cell membrane with release of viral cores into the cytoplasm whereas the light capsids containing dense cores migrated toward the nucleus and accumulated in the perinuclear region. Apparently the process of releasing deoxyribonucleic acid (DNA) from the light capsid is slowed down or prevented in Daudi cells. A hypothesis is presented concerning the manner in which these two types of capsids initiate infection.", "contents": "Electron microscopic studies of tumor viruses. II. Entry and uncoating of Epstein-Barr virus. Entry of Epstein-Barr virus into human lymphoblastoid cells (Daudi cells) was studied by electron microscopy. At the site of viral attachment, two distinct interactions conducive to penetration of the virus occurred between the viral envelope and cell membrane, namely, (i) simultaneous dissolution of both the envelope and cell membrane, presumably resulting in passage of viral capsids into the cytoplasm and (ii) dissolution confined to the cell membrane with resulting penetration of enveloped virus. In the latter case envelope dissolution appears to occur subsequently in the cytoplasm with release of capsids. Fusion of the viral envelope with the cell membrane was not observed. The capsids exhibited two distinct structural forms--one dense, the other translucent or light in appearance. The former disrupted near the cell membrane with release of viral cores into the cytoplasm whereas the light capsids containing dense cores migrated toward the nucleus and accumulated in the perinuclear region. Apparently the process of releasing deoxyribonucleic acid (DNA) from the light capsid is slowed down or prevented in Daudi cells. A hypothesis is presented concerning the manner in which these two types of capsids initiate infection."}
{"id": "PMID:214661", "title": "[A serological survey of rubella among pregnant women in Abidjan (author's transl)].", "content": "A serological survey about the prevalence of the rubella hemagglutination inhibiting antibodies among the pregnant women in Abidjan during the year 1975 has shown an average rate of seroconversion of 84 p. 100. This rate depends on age and increases from 70 to 80 p. 100 between 15 and 35 years old. A regression line is fitted, and the goodness of fit is tested. These rates are in accordance with what is presently observed in America, in Europe and in Australia.", "contents": "[A serological survey of rubella among pregnant women in Abidjan (author's transl)]. A serological survey about the prevalence of the rubella hemagglutination inhibiting antibodies among the pregnant women in Abidjan during the year 1975 has shown an average rate of seroconversion of 84 p. 100. This rate depends on age and increases from 70 to 80 p. 100 between 15 and 35 years old. A regression line is fitted, and the goodness of fit is tested. These rates are in accordance with what is presently observed in America, in Europe and in Australia."}
{"id": "PMID:214662", "title": "[Value of indirect fluorescent tests for on the spot prospection of human African trypanosomiasis (author's transl)].", "content": "The equipment of a laboratory making indirect antibody-fluorescent tests on dried blood blots in the heart of the trypanosomiasis focus of Bouafl\u00e9 (Ivory Coast) gave good results. On a visited population of 1444 people, 13 cases were diagnosed by immunofluorescence tests; 8 were already diagnosed on the spot, trypanosome found in gland juice; 5 were diagnosed following the results of immunofluorescence tests. Reduction of time between sampling and immunological results makes easier the search of suspects. Based on these observations, the writers emphasize the great value of the use of immunofluorescence technics on the spot and the establishment of a regional mobile immunofluorescence team for supplementing the work of local prospection teams.", "contents": "[Value of indirect fluorescent tests for on the spot prospection of human African trypanosomiasis (author's transl)]. The equipment of a laboratory making indirect antibody-fluorescent tests on dried blood blots in the heart of the trypanosomiasis focus of Bouafl\u00e9 (Ivory Coast) gave good results. On a visited population of 1444 people, 13 cases were diagnosed by immunofluorescence tests; 8 were already diagnosed on the spot, trypanosome found in gland juice; 5 were diagnosed following the results of immunofluorescence tests. Reduction of time between sampling and immunological results makes easier the search of suspects. Based on these observations, the writers emphasize the great value of the use of immunofluorescence technics on the spot and the establishment of a regional mobile immunofluorescence team for supplementing the work of local prospection teams."}
{"id": "PMID:214676", "title": "Preparation and efficacy of an inactivated subunit vaccine (NFUIBHK) against type 2 Herpes simplex virus infection.", "content": "A vaccine against Herpes simplex virus infection was prepared by Nonidet NP 40 and formalin treatment of a type 1, infected-cell extract; virus particles were removed by ultracentrifugation over sucrose. These procedures were not detrimental to the antigenic quality of the vaccine preparation. The vaccine afforded significant protection to experimental type 2 genital herpes virus infection in mice, as adjudged by clinical observations, cytopathological change, and virus yields.", "contents": "Preparation and efficacy of an inactivated subunit vaccine (NFUIBHK) against type 2 Herpes simplex virus infection. A vaccine against Herpes simplex virus infection was prepared by Nonidet NP 40 and formalin treatment of a type 1, infected-cell extract; virus particles were removed by ultracentrifugation over sucrose. These procedures were not detrimental to the antigenic quality of the vaccine preparation. The vaccine afforded significant protection to experimental type 2 genital herpes virus infection in mice, as adjudged by clinical observations, cytopathological change, and virus yields."}
{"id": "PMID:214677", "title": "Characterization of proteins of human papilloma viruses (HPV) and antibody response to HPV 1.", "content": "The serological characterization of virus isolates from verrucae vulgares and plantar warts revealed that HPV 1 and HPV 4 are present in about 50% of these warts with HPV 1 being more prevalent, especially in plantar warts. Parallel to the high incidence of HPV 1 infections, about 50% of non-selected young adults contained antibodies against HPV 1. Only HPV 4 particles, however, reacted with serum from a patient with epidermodysplasia verruciformis when tested by immuno-electron microscopy. An examination of HPV 1 proteins indicated that the major structural proteins VP2 and VP3 are trypsin sensitive. Tryptic degradation leads to distinct polypeptides with molecular weights between 37,000 and 23,000 which may be correlated to minor protein components of HPV 1 preparations. HPV 1 histone-like proteins, which co-migrate with purified cellular histones in SDS gel electrophoresis were analyzed in an acetic acid urea system. It was shown that H3- and H4-like proteins differ from cellular histones. The reason for this difference and its meaning are discussed.", "contents": "Characterization of proteins of human papilloma viruses (HPV) and antibody response to HPV 1. The serological characterization of virus isolates from verrucae vulgares and plantar warts revealed that HPV 1 and HPV 4 are present in about 50% of these warts with HPV 1 being more prevalent, especially in plantar warts. Parallel to the high incidence of HPV 1 infections, about 50% of non-selected young adults contained antibodies against HPV 1. Only HPV 4 particles, however, reacted with serum from a patient with epidermodysplasia verruciformis when tested by immuno-electron microscopy. An examination of HPV 1 proteins indicated that the major structural proteins VP2 and VP3 are trypsin sensitive. Tryptic degradation leads to distinct polypeptides with molecular weights between 37,000 and 23,000 which may be correlated to minor protein components of HPV 1 preparations. HPV 1 histone-like proteins, which co-migrate with purified cellular histones in SDS gel electrophoresis were analyzed in an acetic acid urea system. It was shown that H3- and H4-like proteins differ from cellular histones. The reason for this difference and its meaning are discussed."}
{"id": "PMID:214678", "title": "Attempts to isolate virus from human trigeminal and facial ganglions.", "content": "Herpes virus hominis type 1 was isolated from the trigeminal ganglion (ganglion semilunare, gasservian) in three out of 20 randomly selected autopsies. Two of the three patients had been treated with immunosuppressive or cytostatic agents. Clinical signs of herpes infection were not observed during the previous 6 months. No virus was isolated from the facial ganglion (geniculate ganglion) in the same 20 cases. The findings are discussed in relation to the viral etiology of acute peripheral facial palsy.", "contents": "Attempts to isolate virus from human trigeminal and facial ganglions. Herpes virus hominis type 1 was isolated from the trigeminal ganglion (ganglion semilunare, gasservian) in three out of 20 randomly selected autopsies. Two of the three patients had been treated with immunosuppressive or cytostatic agents. Clinical signs of herpes infection were not observed during the previous 6 months. No virus was isolated from the facial ganglion (geniculate ganglion) in the same 20 cases. The findings are discussed in relation to the viral etiology of acute peripheral facial palsy."}
{"id": "PMID:214679", "title": "Comparison of five diagnostic methods for the detection of rotavirus antigens in calf faeces.", "content": "Immunoelectroosmophoresis, complement fixation, immunofluorescence on inoculated cell cultures, electron microscopy, and an enzyme-linked immunosorbent assay were compared for the detection of rotavirus in faecal samples from calves. Rotavirus particles could be detected in 39 out of 98 faecal samples by electron microscopy. Immunofluorescence, complement fixation, and immunoelectroosmophoresis detected rotavirus antigens in 39, 42, and 30 samples, respectively. The enzyme-linked immunosorbent assay demonstrated rotavirus antigens in 49 faecal samples. The assay is not only sensitive but also simple to perform and suitable for large-scale testing.", "contents": "Comparison of five diagnostic methods for the detection of rotavirus antigens in calf faeces. Immunoelectroosmophoresis, complement fixation, immunofluorescence on inoculated cell cultures, electron microscopy, and an enzyme-linked immunosorbent assay were compared for the detection of rotavirus in faecal samples from calves. Rotavirus particles could be detected in 39 out of 98 faecal samples by electron microscopy. Immunofluorescence, complement fixation, and immunoelectroosmophoresis detected rotavirus antigens in 39, 42, and 30 samples, respectively. The enzyme-linked immunosorbent assay demonstrated rotavirus antigens in 49 faecal samples. The assay is not only sensitive but also simple to perform and suitable for large-scale testing."}
{"id": "PMID:214680", "title": "Nonspecific inhibitors of coronavirus OC43 haemagglutination in human sera.", "content": "Antibodies against the human coronavirus OC43 in human sera were measured by haemagglutination inhibition (HI), complement fixation (CF), and radial diffusion-haemolysis in gel (HIG) techniques. The apparent HI titres in a fraction of sera with no antibodies detectable by the two other methods were found to be reduced considerably after treating the sera with phospholipase C (PLC). The PLC treatment also reduced the apparent HI titres in some sera containing variable amounts of CF and/or HIG antibodies, but did not affect antibody determinations by the two latter methods. These results suggest that false positive results can be obtained in the OC43 HI test unless the sera are treated with phospholipase C before the assay.", "contents": "Nonspecific inhibitors of coronavirus OC43 haemagglutination in human sera. Antibodies against the human coronavirus OC43 in human sera were measured by haemagglutination inhibition (HI), complement fixation (CF), and radial diffusion-haemolysis in gel (HIG) techniques. The apparent HI titres in a fraction of sera with no antibodies detectable by the two other methods were found to be reduced considerably after treating the sera with phospholipase C (PLC). The PLC treatment also reduced the apparent HI titres in some sera containing variable amounts of CF and/or HIG antibodies, but did not affect antibody determinations by the two latter methods. These results suggest that false positive results can be obtained in the OC43 HI test unless the sera are treated with phospholipase C before the assay."}
{"id": "PMID:214681", "title": "Application of a solid-phase radioimmunoassay and immune electron microscopy for hepatitis A in diagnosis and research.", "content": "With crude virus suspensions from stool and antibodies from hepatitis-A patients, a solid-phase radioimmunoassay (RIA) for detection of hepatitis virus A (HVA) had antibodies against hepatitis virus A (anti-HVA) has been developed. Examples for the application of this test are demonstrated. Virus particles from the stools of the two patients were further characterized. Serologically, they were identical or very similar to the MS-1 strain. Isopycnic CsCl-gradient centrifugation of both strains revealed two peaks, but the particles of different densities did not differ in size or serologically. A modification of the RIA was also useful for determination of IgM antibodies in patients' sera fractionated by sucrose-density centrifugation. The application of the RIA method for serologic epidemiology is demonstrated by a comparison of anti-HVA prevalence in German and non-German women residing in Germany.", "contents": "Application of a solid-phase radioimmunoassay and immune electron microscopy for hepatitis A in diagnosis and research. With crude virus suspensions from stool and antibodies from hepatitis-A patients, a solid-phase radioimmunoassay (RIA) for detection of hepatitis virus A (HVA) had antibodies against hepatitis virus A (anti-HVA) has been developed. Examples for the application of this test are demonstrated. Virus particles from the stools of the two patients were further characterized. Serologically, they were identical or very similar to the MS-1 strain. Isopycnic CsCl-gradient centrifugation of both strains revealed two peaks, but the particles of different densities did not differ in size or serologically. A modification of the RIA was also useful for determination of IgM antibodies in patients' sera fractionated by sucrose-density centrifugation. The application of the RIA method for serologic epidemiology is demonstrated by a comparison of anti-HVA prevalence in German and non-German women residing in Germany."}
{"id": "PMID:214682", "title": "Epstein-Barr virus early antigen titer by immunofluorescence in microplates. A new semi-automated method based on microtiter system.", "content": "For the titration of antibodies directed against Epstein-Barr Virus early antigen (EBV-EA) we describe a method in microplates with the Microtiter System (Cooke Engineering Co., Alexandria, Va). Using this technique, which allows rapid epidemiological investigations, we have titered anti-EBV-EA antibodies in different groups of patients and controls, and particularly in group which had recent contact with infectious mononucleosis. In this group the percentage of individuals having antibodies directed against the EBV-EA antigen was significantly higher than in the group of controls.", "contents": "Epstein-Barr virus early antigen titer by immunofluorescence in microplates. A new semi-automated method based on microtiter system. For the titration of antibodies directed against Epstein-Barr Virus early antigen (EBV-EA) we describe a method in microplates with the Microtiter System (Cooke Engineering Co., Alexandria, Va). Using this technique, which allows rapid epidemiological investigations, we have titered anti-EBV-EA antibodies in different groups of patients and controls, and particularly in group which had recent contact with infectious mononucleosis. In this group the percentage of individuals having antibodies directed against the EBV-EA antigen was significantly higher than in the group of controls."}
{"id": "PMID:214683", "title": "The proteins of varicella-zoster-virus.", "content": "[35S] methionine-labelled Varicella-Zoster-Virus (VZV) was partly purified by sucrose density gradient centrifugation. Enveloped virus, checked by electron microscopy, was analyzed by high resolution polyacrylamide gel electrophoresis. A polypeptide pattern of at least 31 proteins could be identified on the fluorogram. The molecular weight of the proteins, estimated by co-electrophoresis with marker proteins, ranged from 18,000 to 240,000 daltons. Immunoprecipitation using a specific human antiserum showed at least 14 proteins.", "contents": "The proteins of varicella-zoster-virus. [35S] methionine-labelled Varicella-Zoster-Virus (VZV) was partly purified by sucrose density gradient centrifugation. Enveloped virus, checked by electron microscopy, was analyzed by high resolution polyacrylamide gel electrophoresis. A polypeptide pattern of at least 31 proteins could be identified on the fluorogram. The molecular weight of the proteins, estimated by co-electrophoresis with marker proteins, ranged from 18,000 to 240,000 daltons. Immunoprecipitation using a specific human antiserum showed at least 14 proteins."}
{"id": "PMID:214684", "title": "HBsAg-negative chronic active hepatitis related to hepatitis B virus.", "content": "Numerous cases of chronic hepatitis have been shown to be closely associated with persistent infection with hepatitis B virus (HBV). A group of 100 patients suffering from chronic active hepatitis (CAH) was investigated for HBV serologic markers. Of these, 35 patients were HbsAg-positive; in 26 HBsAg-negative subjects, anti-HBc were detected using counterimmune electrophoresis and complement-fixation tests. These data suggest that chronic liver disease in patients who were only anti-HBc-positive might be related to persistent infection with hepatitis B virus. Epidemiological clinical and histopathological data were different when we compared CAH patients who were HBsAg-negative, but anti-HBc-positive, with HBsAg-positive CAH patients. A sequence is proposed leading from HBsAg-positive to HBsAg-negative CAH, cirrhosis, and hepatoma in temperate areas, according to a model similar to the one described in intertropical Africa.", "contents": "HBsAg-negative chronic active hepatitis related to hepatitis B virus. Numerous cases of chronic hepatitis have been shown to be closely associated with persistent infection with hepatitis B virus (HBV). A group of 100 patients suffering from chronic active hepatitis (CAH) was investigated for HBV serologic markers. Of these, 35 patients were HbsAg-positive; in 26 HBsAg-negative subjects, anti-HBc were detected using counterimmune electrophoresis and complement-fixation tests. These data suggest that chronic liver disease in patients who were only anti-HBc-positive might be related to persistent infection with hepatitis B virus. Epidemiological clinical and histopathological data were different when we compared CAH patients who were HBsAg-negative, but anti-HBc-positive, with HBsAg-positive CAH patients. A sequence is proposed leading from HBsAg-positive to HBsAg-negative CAH, cirrhosis, and hepatoma in temperate areas, according to a model similar to the one described in intertropical Africa."}
{"id": "PMID:214686", "title": "Physical characterization of deoxyribonucleic acids of different human papilloma viruses (HPV).", "content": "Different types of human papilloma viruses (HPV) had been identified by the use of bacterial restriction endonucleases (Gissmann et al., 1977). The DNAs of HPV 1, 2, and 3 showing a similar restriction enzyme pattern can be purified in sufficient quantities to permit further characterization. These viruses appear not to be identical, as far as molecular weight (4.9 X 10(6) d), buoyant density (1.700 mu/ml), and sedimentation values of the different DNA components (Co I: 22--23S; Co II: 17S; Co III: 16S) are concerned. HPV 4 DNA, which is entirely different from HPV 1--3 in its restriction enzyme pattern, does not hybridize with cRNA transcribed in vitro from HPV 1 DNA. The cRNA was shown to represent the whole viral genome.", "contents": "Physical characterization of deoxyribonucleic acids of different human papilloma viruses (HPV). Different types of human papilloma viruses (HPV) had been identified by the use of bacterial restriction endonucleases (Gissmann et al., 1977). The DNAs of HPV 1, 2, and 3 showing a similar restriction enzyme pattern can be purified in sufficient quantities to permit further characterization. These viruses appear not to be identical, as far as molecular weight (4.9 X 10(6) d), buoyant density (1.700 mu/ml), and sedimentation values of the different DNA components (Co I: 22--23S; Co II: 17S; Co III: 16S) are concerned. HPV 4 DNA, which is entirely different from HPV 1--3 in its restriction enzyme pattern, does not hybridize with cRNA transcribed in vitro from HPV 1 DNA. The cRNA was shown to represent the whole viral genome."}
{"id": "PMID:214687", "title": "Genetic susceptibility to wild and vaccine polio virus: genotypes and their frequency.", "content": "The frequency of proposed genotypes which predispose to poliomyelitis, is tabled. Susceptibility is due to a gene or linkage group of genes with a frequency of 2% for the homozygote and 24% for the heterozygote. Two subgroups are identified where a second gene might make the persons susceptible to vaccine strains of virus. Cutter vaccinees might form a third group with increased susceptibility under special circumstances. The age at which genetic susceptibility changes to phenotypic susceptibility may be modified by physical factors such as those due to congenital syphilis and Salvarsan, and thalidomide.", "contents": "Genetic susceptibility to wild and vaccine polio virus: genotypes and their frequency. The frequency of proposed genotypes which predispose to poliomyelitis, is tabled. Susceptibility is due to a gene or linkage group of genes with a frequency of 2% for the homozygote and 24% for the heterozygote. Two subgroups are identified where a second gene might make the persons susceptible to vaccine strains of virus. Cutter vaccinees might form a third group with increased susceptibility under special circumstances. The age at which genetic susceptibility changes to phenotypic susceptibility may be modified by physical factors such as those due to congenital syphilis and Salvarsan, and thalidomide."}
{"id": "PMID:214688", "title": "Protection of guinea pigs against primary and recurrent genital herpes infections by immunization with live heterologous or homologous Herpes simplex virus: implications for a herpes virus vaccine.", "content": "Guinea pigs, inoculated intravaginally with HSV type 2 develop a primary and spontaneously recurring genital herpes with clinical symptoms resembling genital herpes in humans. The effect of a previous infection with either HSV type 1 or HSV type 2 on the clinical course of the intravaginal challenge infection was studied. Prior infection with either subtype of HSV moderated considerably the acute disease induced by intravaginal HSV type 2 challenge. No effect was, however, observed on the development of the chronic phase of the challenge infection. The significance of these studies for the possibility of vaccination against recurrent herpes infections is discussed.", "contents": "Protection of guinea pigs against primary and recurrent genital herpes infections by immunization with live heterologous or homologous Herpes simplex virus: implications for a herpes virus vaccine. Guinea pigs, inoculated intravaginally with HSV type 2 develop a primary and spontaneously recurring genital herpes with clinical symptoms resembling genital herpes in humans. The effect of a previous infection with either HSV type 1 or HSV type 2 on the clinical course of the intravaginal challenge infection was studied. Prior infection with either subtype of HSV moderated considerably the acute disease induced by intravaginal HSV type 2 challenge. No effect was, however, observed on the development of the chronic phase of the challenge infection. The significance of these studies for the possibility of vaccination against recurrent herpes infections is discussed."}
{"id": "PMID:214689", "title": "Stimulation of human lymphocytes by cytomegalovirions and dense bodies.", "content": "Lymphocytes from healthy adult individuals were examined for their ability to incorporate thymidine in the presence of cytomegalovirus (CMV) and dense bodies. It was found that lymphocytes from donors with antibodies to CMV were stimulated to incorporate thymidine-14C both by preparation of CMV and CMV dense bodies. Lymphocytes from CMV seronegative donors did not respond. Dilution experiments and the dose-response curve indicate that the stimulation induced by the dense body preparation was not caused by the small amounts of contaminating CMV particles. These results indicate that in healthy human adults there is a correlation between CMV seropositivity and in vitro lymphocyte transformation, induced by either CMV or by dense bodies.", "contents": "Stimulation of human lymphocytes by cytomegalovirions and dense bodies. Lymphocytes from healthy adult individuals were examined for their ability to incorporate thymidine in the presence of cytomegalovirus (CMV) and dense bodies. It was found that lymphocytes from donors with antibodies to CMV were stimulated to incorporate thymidine-14C both by preparation of CMV and CMV dense bodies. Lymphocytes from CMV seronegative donors did not respond. Dilution experiments and the dose-response curve indicate that the stimulation induced by the dense body preparation was not caused by the small amounts of contaminating CMV particles. These results indicate that in healthy human adults there is a correlation between CMV seropositivity and in vitro lymphocyte transformation, induced by either CMV or by dense bodies."}
{"id": "PMID:214690", "title": "Primary chemotherapeutic management of unresectable and metastatic hepatoblastoma in children: report of four cases.", "content": "Four children presenting with unresectable hepatoblastomas and one with metastatic disease are reported. Following initial biopsy all were treated with chemotherapy which included Adriamycin. Three of the four children showed a significant reduction in tumor size, and in two, delayed resection of the primary lesion was possible. Chemotherapy including Adriamycin represents effective initial cytoreductive therapy for childhood hepatoblastoma, thereby reducing the morbidity and mortality associated with the extensive hepatic resection usually required for an untreated lesion.", "contents": "Primary chemotherapeutic management of unresectable and metastatic hepatoblastoma in children: report of four cases. Four children presenting with unresectable hepatoblastomas and one with metastatic disease are reported. Following initial biopsy all were treated with chemotherapy which included Adriamycin. Three of the four children showed a significant reduction in tumor size, and in two, delayed resection of the primary lesion was possible. Chemotherapy including Adriamycin represents effective initial cytoreductive therapy for childhood hepatoblastoma, thereby reducing the morbidity and mortality associated with the extensive hepatic resection usually required for an untreated lesion."}
{"id": "PMID:214691", "title": "Prevention of brain extension in small-cell carcinoma of the bronchus.", "content": "In small-cell carcinoma of the bronchus, extension to the brain is common. The role of prophylactic whole-brain irradiation and combination chemotherapy using CCNU in the prevention of brain extension is examined in the light of recent studies.", "contents": "Prevention of brain extension in small-cell carcinoma of the bronchus. In small-cell carcinoma of the bronchus, extension to the brain is common. The role of prophylactic whole-brain irradiation and combination chemotherapy using CCNU in the prevention of brain extension is examined in the light of recent studies."}
{"id": "PMID:214692", "title": "Treatment of oat-cell carcinoma of the lung in the community.", "content": "Nine patients with \"limited\" (thoracic) small-cell lung carcinoma were treated with combined chemotherapy and radiotherapy (involved field and prophylactic whole brain). Induction drugs were Vincristine, Adriamycin, and Cyclophosphamide; and Cyclophosphamide, Vincristine, and CCNU for maintenance. Eight out of nine patients (89%) continue NED at a median follow-up time of 12 months. This group is compared to 21 patients with more extensive disease and 6 patients with limited disease using various other regimens. Median survival in the extensive group was 5 months and 8 months for the limited-diseased group treated with single agents. Intensive combination chemo-irradiation therapy is safe and highly effective in patients with limited oat-cell carcinoma of the lung, and leads to prolonged disease-free survival.", "contents": "Treatment of oat-cell carcinoma of the lung in the community. Nine patients with \"limited\" (thoracic) small-cell lung carcinoma were treated with combined chemotherapy and radiotherapy (involved field and prophylactic whole brain). Induction drugs were Vincristine, Adriamycin, and Cyclophosphamide; and Cyclophosphamide, Vincristine, and CCNU for maintenance. Eight out of nine patients (89%) continue NED at a median follow-up time of 12 months. This group is compared to 21 patients with more extensive disease and 6 patients with limited disease using various other regimens. Median survival in the extensive group was 5 months and 8 months for the limited-diseased group treated with single agents. Intensive combination chemo-irradiation therapy is safe and highly effective in patients with limited oat-cell carcinoma of the lung, and leads to prolonged disease-free survival."}
{"id": "PMID:214695", "title": "Specific effect of zinc ions on DNA polymerase activity of avian myeloblastosis virus.", "content": "The effect of selected cations on DNA synthesis by DNA-polymerase of avian myeloblastosis virus (AMV) was studied. Zinc ions at low concentration (0.2mM) in the assay system enhanced the activity about 2 x fold and at higher concentration (2.0 mM) inhibited the activity completely. In contrast, addition of lithium and potassium salts produced inhibitory effects in this ionic concentration range. Replacement of K+ ion had an inhibitory effect on the activity.", "contents": "Specific effect of zinc ions on DNA polymerase activity of avian myeloblastosis virus. The effect of selected cations on DNA synthesis by DNA-polymerase of avian myeloblastosis virus (AMV) was studied. Zinc ions at low concentration (0.2mM) in the assay system enhanced the activity about 2 x fold and at higher concentration (2.0 mM) inhibited the activity completely. In contrast, addition of lithium and potassium salts produced inhibitory effects in this ionic concentration range. Replacement of K+ ion had an inhibitory effect on the activity."}
{"id": "PMID:214696", "title": "[alpha1-antitrypsin deficiency. Clinical and morphological aspects during childhood (author's transl)].", "content": "In many cases so called neonatal hepatitis of unknown origin nowadays is recognized as a manifestation of alpha1-antitrypsin deficiency. Out of 12 patients with Pi-type ZZ, 5 were diagnosed because of cholestatic jaundice, 2 because of hepato-splenomegaly in the first trimenon, and 3 by family examination. We believe that the affection may be due to a perinataly acquired cytomegalic inclusion disease in one case, in another to a congenital rubella infection. The latter child died at the age of one year because of an esophageal hemorrhage. Over a mean observation time of 3 years the other patients are doing well and show no signs of portal hypertension. The very different course of the hepatopathy is demonstrated. Common bacteria or toxins which do not usually lead to an illness may be realisation factors just as \"classical\" causes of hepatitis. Up to now it is not known how these factors influence the course of alpha-antitrypsin deficiency.", "contents": "[alpha1-antitrypsin deficiency. Clinical and morphological aspects during childhood (author's transl)]. In many cases so called neonatal hepatitis of unknown origin nowadays is recognized as a manifestation of alpha1-antitrypsin deficiency. Out of 12 patients with Pi-type ZZ, 5 were diagnosed because of cholestatic jaundice, 2 because of hepato-splenomegaly in the first trimenon, and 3 by family examination. We believe that the affection may be due to a perinataly acquired cytomegalic inclusion disease in one case, in another to a congenital rubella infection. The latter child died at the age of one year because of an esophageal hemorrhage. Over a mean observation time of 3 years the other patients are doing well and show no signs of portal hypertension. The very different course of the hepatopathy is demonstrated. Common bacteria or toxins which do not usually lead to an illness may be realisation factors just as \"classical\" causes of hepatitis. Up to now it is not known how these factors influence the course of alpha-antitrypsin deficiency."}
{"id": "PMID:214701", "title": "[Dose-effect of beta-sitosterin in type IIa and IIb hypercholesterolemias (author's transl)].", "content": "In a trial with 59 outpatients with hypercholesterolemia the effect of two different doses of 5.28 and 10,56 g Beta-Sitosterol was compared to placebo. Each treatment phase lasted six weeks. Serum cholesterol decreased on the average under Beta-Sitosterol by 10--13% (p less than 0.05) in correlation with LDL. The triglycerides were not affected; there was a slight increase in the HDL/LDL quotient. The optimal daily dose of Beta-Sitosterol was about 6 gm; the double dose was no more effective.", "contents": "[Dose-effect of beta-sitosterin in type IIa and IIb hypercholesterolemias (author's transl)]. In a trial with 59 outpatients with hypercholesterolemia the effect of two different doses of 5.28 and 10,56 g Beta-Sitosterol was compared to placebo. Each treatment phase lasted six weeks. Serum cholesterol decreased on the average under Beta-Sitosterol by 10--13% (p less than 0.05) in correlation with LDL. The triglycerides were not affected; there was a slight increase in the HDL/LDL quotient. The optimal daily dose of Beta-Sitosterol was about 6 gm; the double dose was no more effective."}
{"id": "PMID:214706", "title": "Perturbations in simian virus 40 DNA synthesis by ultraviolet light.", "content": "Perturbations of Simian Virus 40 (SV40) DNA replication by ultraviolet (UV) light during the lytic cycle in permissive monkey CV-1 cells resemble those seen in host cell DNA replication. Formation of Form I DNA molecules (i.e. completion of SV40 DNA synthesis) was more sensitive to UV irradiation than synthesis of replicative intermediates or Form II molecules, consistent with inhibition of DNA chain elongation. The observed amounts of [3H]thymidine incorporated in UV-irradiated molecules could be predicted on the assumption that pyrimidine dimers are responsible for blocking nascent DNA strand growth. The relative proportion of labeled Form I molecules in UV-irradiated cultures rapidly increased to near-control values with incubation after 20 or 40 J/m2 of light (0.9--1.0 or 1.8--2.0 dimers per SV40 genome, respectively). This rapid increase and the failure of Form II molecules to accumulate suggest that SV40 growing forks can rapidly bypass many dimers. Form II molecules formed after UV irradiation were not converted to linear (Form III) molecules by the dimer-specific T4 endonuclease V, suggesting either that there are no gaps opposite dimers in these molecules or that T4 endonuclease V cannot use Form II molecules as substrates.", "contents": "Perturbations in simian virus 40 DNA synthesis by ultraviolet light. Perturbations of Simian Virus 40 (SV40) DNA replication by ultraviolet (UV) light during the lytic cycle in permissive monkey CV-1 cells resemble those seen in host cell DNA replication. Formation of Form I DNA molecules (i.e. completion of SV40 DNA synthesis) was more sensitive to UV irradiation than synthesis of replicative intermediates or Form II molecules, consistent with inhibition of DNA chain elongation. The observed amounts of [3H]thymidine incorporated in UV-irradiated molecules could be predicted on the assumption that pyrimidine dimers are responsible for blocking nascent DNA strand growth. The relative proportion of labeled Form I molecules in UV-irradiated cultures rapidly increased to near-control values with incubation after 20 or 40 J/m2 of light (0.9--1.0 or 1.8--2.0 dimers per SV40 genome, respectively). This rapid increase and the failure of Form II molecules to accumulate suggest that SV40 growing forks can rapidly bypass many dimers. Form II molecules formed after UV irradiation were not converted to linear (Form III) molecules by the dimer-specific T4 endonuclease V, suggesting either that there are no gaps opposite dimers in these molecules or that T4 endonuclease V cannot use Form II molecules as substrates."}
{"id": "PMID:214716", "title": "The enkephalins. Peptides with morphine-like activity.", "content": "Two penta-peptides with morphine-like properties have recently been found in the nervous system and gastrointestinal tract. These peptides known as enkephalins are unevenly distributed in the brain, the highest concentration being in the globus pallidus. The enkephalins are found to have analgesic properties and are also anti-tussive, anti-diarrheal and able to stimulate release of prolactin and growth hormone. Synthetic analogues of the enkephalins containing specific D-amino acid substitutions have been developed and show a wide spectrum of activities.", "contents": "The enkephalins. Peptides with morphine-like activity. Two penta-peptides with morphine-like properties have recently been found in the nervous system and gastrointestinal tract. These peptides known as enkephalins are unevenly distributed in the brain, the highest concentration being in the globus pallidus. The enkephalins are found to have analgesic properties and are also anti-tussive, anti-diarrheal and able to stimulate release of prolactin and growth hormone. Synthetic analogues of the enkephalins containing specific D-amino acid substitutions have been developed and show a wide spectrum of activities."}
{"id": "PMID:214718", "title": "Site of naloxone-precipitated opiate withdrawal dissociates from that at which apomorphine reinitiates this phenomenon.", "content": "The site of action of naloxone to induce jumping in morphine tolerant/dependent rats appears to be dissociated from structures where apomorphine initiates its action to reinduce jumping in previously withdrawn animals. These findings suggest that dopaminergic pathways do not directly affect the neuronal circuit involved in withdrawal jumping behavior, but instead exert a facilitatory influence on neurons that become supersensitive during the state of withdrawal. Thus, an increased response to apomorphine during naloxone-precipitated opiate withdrawal does not necessarily imply a specific supersensitivity of the dopaminergic system.", "contents": "Site of naloxone-precipitated opiate withdrawal dissociates from that at which apomorphine reinitiates this phenomenon. The site of action of naloxone to induce jumping in morphine tolerant/dependent rats appears to be dissociated from structures where apomorphine initiates its action to reinduce jumping in previously withdrawn animals. These findings suggest that dopaminergic pathways do not directly affect the neuronal circuit involved in withdrawal jumping behavior, but instead exert a facilitatory influence on neurons that become supersensitive during the state of withdrawal. Thus, an increased response to apomorphine during naloxone-precipitated opiate withdrawal does not necessarily imply a specific supersensitivity of the dopaminergic system."}
{"id": "PMID:214725", "title": "[Benign childhood epilepsy with spike activity in the area of the precentral gyrus].", "content": "The authors report 18 cases of benign childhood epilepsy with spike activity in the Rolandic area. These cases were isolated from a group of 103 children with partial epilepsy. In agreement with the observations of other authors the benign course of this form of epilepsy is stressed. The isolation of this type of epilepsy is necessary in view of its practical management, treatment and prognosis. Neuroradiological and neurological examinations failed to demonstrate any evidence of organic brain disease in this epilepsy. Focal EEG changes with spike activity in the frontal or temporal area regressed gradually until complete normalization of the record. The authors agree with the view of other authors that the diagnosis of this epilepsy in typical from does not require radioneurological contrast investigations.", "contents": "[Benign childhood epilepsy with spike activity in the area of the precentral gyrus]. The authors report 18 cases of benign childhood epilepsy with spike activity in the Rolandic area. These cases were isolated from a group of 103 children with partial epilepsy. In agreement with the observations of other authors the benign course of this form of epilepsy is stressed. The isolation of this type of epilepsy is necessary in view of its practical management, treatment and prognosis. Neuroradiological and neurological examinations failed to demonstrate any evidence of organic brain disease in this epilepsy. Focal EEG changes with spike activity in the frontal or temporal area regressed gradually until complete normalization of the record. The authors agree with the view of other authors that the diagnosis of this epilepsy in typical from does not require radioneurological contrast investigations."}
{"id": "PMID:214729", "title": "Steroid hormones in ovarian vein and cyst fluid of a virilizing stromal tumor.", "content": "A 23-year-old female with clinical signs of excessive androgen and estrogen production was found to have a gonadal stromal tumor. The clinical symptoms correlated well with steroid hormone values in ovarian vein blood and ovarian cyst fluid of the ovarian tumor. Ovarian vein blood draining the ovarian tumor measured as follows: estrone, 162 pg/ml; estradiol, 1688 pg/ml; progesterone, 9.6 ng/ml; testosterone, 9775 ng/100 ml; and dihydrotestosterone, 2905 ng/100 ml. The ovarian cyst fluid produced higher estrogen and lower androgen values compared with ipsilateral ovarian vein blood. Peripheral levels of immunoreactive testosterone ranged from 210 to 244 ng/100 ml. It is concluded that excessive androgen and estrogen production may arise from a gonadal stromal tumor that has been previously classified as a purely virilizing ovarian tumor.", "contents": "Steroid hormones in ovarian vein and cyst fluid of a virilizing stromal tumor. A 23-year-old female with clinical signs of excessive androgen and estrogen production was found to have a gonadal stromal tumor. The clinical symptoms correlated well with steroid hormone values in ovarian vein blood and ovarian cyst fluid of the ovarian tumor. Ovarian vein blood draining the ovarian tumor measured as follows: estrone, 162 pg/ml; estradiol, 1688 pg/ml; progesterone, 9.6 ng/ml; testosterone, 9775 ng/100 ml; and dihydrotestosterone, 2905 ng/100 ml. The ovarian cyst fluid produced higher estrogen and lower androgen values compared with ipsilateral ovarian vein blood. Peripheral levels of immunoreactive testosterone ranged from 210 to 244 ng/100 ml. It is concluded that excessive androgen and estrogen production may arise from a gonadal stromal tumor that has been previously classified as a purely virilizing ovarian tumor."}
{"id": "PMID:214730", "title": "Colposcopic examination of the cervix of cebus monkeys.", "content": "A total of 410 colposcopic examinations were performed on 188 female cebus monkeys that were under study to determine the oncogenic potential of herpes simplex virus type 2 in this genus. A split-cone vaginal speculum was developed that permitted good observation of the vaginal cervix in the cebus monkey. The cervical anatomy of cebus monkeys was found to differ from that of humans in that the surface of the animal cervix was more papilliform, with thinner squamous epithelium, and the squamocolumnar junction lay within the endocervical canal. Therefore, the ability to detect abnormalities in the cervical epithelium by colposcopic examination in the cebus monkey was restricted to vascular changes in the squamous epithelium. After 100 examinations, several vascular patterns were distinguishable and interpretations of these patterns were compared with cytologic findings on the same animals. Findings by both cytology and colposcopy were mild in nature; no carcinoma was detected. Colposcopic and cytologic findings correlated at a level of 84%. More abnormalities were detected with colposcopy than with use of cytologic techniques.", "contents": "Colposcopic examination of the cervix of cebus monkeys. A total of 410 colposcopic examinations were performed on 188 female cebus monkeys that were under study to determine the oncogenic potential of herpes simplex virus type 2 in this genus. A split-cone vaginal speculum was developed that permitted good observation of the vaginal cervix in the cebus monkey. The cervical anatomy of cebus monkeys was found to differ from that of humans in that the surface of the animal cervix was more papilliform, with thinner squamous epithelium, and the squamocolumnar junction lay within the endocervical canal. Therefore, the ability to detect abnormalities in the cervical epithelium by colposcopic examination in the cebus monkey was restricted to vascular changes in the squamous epithelium. After 100 examinations, several vascular patterns were distinguishable and interpretations of these patterns were compared with cytologic findings on the same animals. Findings by both cytology and colposcopy were mild in nature; no carcinoma was detected. Colposcopic and cytologic findings correlated at a level of 84%. More abnormalities were detected with colposcopy than with use of cytologic techniques."}
{"id": "PMID:214732", "title": "The value of levamisole in a Wilms' tumor animal model.", "content": "The effect of Levamisole was studied in an animal model of Wilms' tumor. No tumoridical effect of Levamisol could be documented in this tumor model, and no effect was shown on prevention of tumor, when Levamisole was given before tumor implantation. In previous experience with Wilms' tumor model, a good correlation between the human and animal tumor was found in regard to treatment with different drugs. The fact that Levamisole had no effect on our animal model and its reported immunosuppressive effect at some doses, should be considered in planning clinical trials.", "contents": "The value of levamisole in a Wilms' tumor animal model. The effect of Levamisole was studied in an animal model of Wilms' tumor. No tumoridical effect of Levamisol could be documented in this tumor model, and no effect was shown on prevention of tumor, when Levamisole was given before tumor implantation. In previous experience with Wilms' tumor model, a good correlation between the human and animal tumor was found in regard to treatment with different drugs. The fact that Levamisole had no effect on our animal model and its reported immunosuppressive effect at some doses, should be considered in planning clinical trials."}
{"id": "PMID:214734", "title": "Quartz fibers as templates for biopolymers.", "content": "The polymerization of silica in water solution to form quartz fibers proceeds by a dehydration process, analogous to condensation polymerization in organic high-polymers, in which monomeric Si(OH)4 groups unite through Si--O--Si bonds with the elimination of H2O. The resulting fibers are structurally polar along the direction of elongation, are enantiomorphous, and generally show stereospecific twisting around the direction of elongation. In these regards the fibers are analogues of biopolymers such as RNA and DNA. Quartz also possesses specific adsorptive relations to a wide range of organic substances including monomer amino acids, short-chain polypeptides, and proteins. These involve hydrogen-bonding between (OH) or silanol groups on the surface of the quartz with active side-groups on the organic molecules, and in part are epitaxial through dimensional coincidences in the interface. Geochemical evidence indicates that quartz was deposited in the early Precambrian ocean either by direct crystallization from seawater or by recrystallization of amorphous silica. What is of interest is the possible role of quartz fibers as a template and co-polymer in the passage of biomonomers in the pre-biotic ocean to the long-chain biopolymers such as nucleic acids and proteins that are involved in life processes.", "contents": "Quartz fibers as templates for biopolymers. The polymerization of silica in water solution to form quartz fibers proceeds by a dehydration process, analogous to condensation polymerization in organic high-polymers, in which monomeric Si(OH)4 groups unite through Si--O--Si bonds with the elimination of H2O. The resulting fibers are structurally polar along the direction of elongation, are enantiomorphous, and generally show stereospecific twisting around the direction of elongation. In these regards the fibers are analogues of biopolymers such as RNA and DNA. Quartz also possesses specific adsorptive relations to a wide range of organic substances including monomer amino acids, short-chain polypeptides, and proteins. These involve hydrogen-bonding between (OH) or silanol groups on the surface of the quartz with active side-groups on the organic molecules, and in part are epitaxial through dimensional coincidences in the interface. Geochemical evidence indicates that quartz was deposited in the early Precambrian ocean either by direct crystallization from seawater or by recrystallization of amorphous silica. What is of interest is the possible role of quartz fibers as a template and co-polymer in the passage of biomonomers in the pre-biotic ocean to the long-chain biopolymers such as nucleic acids and proteins that are involved in life processes."}
{"id": "PMID:214735", "title": "Degradation of biochemical activity in soil sterilized by dry heat and gamma radiation.", "content": "The activities of three enzymes present in soil, phosphatases, urease, and decarboxylase, were monitered as indicators of the loss of biochemical information occurring when soil was sterilized by dry heat (0.08% relative humidity), gamma radiation, or a combination of both. More enzymatic activity was retained in soil sterilized by a long exposure to dry heat at relatively low temperature (8 weeks at 100.5 degrees C) than by a shorter exposure to a higher temperature (2 weeks at 124.5 degrees C). No enzymatic activity was detectable in soil sterilized by an even higher temperature (4 days at 148.5 degrees C). Soil sterilized with 7.5 Mrads of radiation retained much higher enzymatic activity than with heat sterilization. Combining sublethal doses of heat radiation effectively sterilized the soil and yielded enzymatic activities higher than those of soil sterilized by dry heat alone but lower than those of soil sterilized by radiation.", "contents": "Degradation of biochemical activity in soil sterilized by dry heat and gamma radiation. The activities of three enzymes present in soil, phosphatases, urease, and decarboxylase, were monitered as indicators of the loss of biochemical information occurring when soil was sterilized by dry heat (0.08% relative humidity), gamma radiation, or a combination of both. More enzymatic activity was retained in soil sterilized by a long exposure to dry heat at relatively low temperature (8 weeks at 100.5 degrees C) than by a shorter exposure to a higher temperature (2 weeks at 124.5 degrees C). No enzymatic activity was detectable in soil sterilized by an even higher temperature (4 days at 148.5 degrees C). Soil sterilized with 7.5 Mrads of radiation retained much higher enzymatic activity than with heat sterilization. Combining sublethal doses of heat radiation effectively sterilized the soil and yielded enzymatic activities higher than those of soil sterilized by dry heat alone but lower than those of soil sterilized by radiation."}
{"id": "PMID:214736", "title": "The role of interferon in virus infections and antibody formation.", "content": "Virus-type interferon is capable of suppressing the antibody response both in vivo and in vitro. Interferon induced by antigen or mitogen (immune interferon), primarily in T-lymphocytes, also appears capable of suppressing the antibody response. Cyclic AMP has a regulatory effect on the induction of both virus-type and immune interferon. The immunosuppressive effects of virus-type and immune interferon may differ at the cellular or subcellular level.", "contents": "The role of interferon in virus infections and antibody formation. Virus-type interferon is capable of suppressing the antibody response both in vivo and in vitro. Interferon induced by antigen or mitogen (immune interferon), primarily in T-lymphocytes, also appears capable of suppressing the antibody response. Cyclic AMP has a regulatory effect on the induction of both virus-type and immune interferon. The immunosuppressive effects of virus-type and immune interferon may differ at the cellular or subcellular level."}
{"id": "PMID:214733", "title": "Calcification within metastatic pulmonary nodules from synovial sarcoma.", "content": "A case of calcified metastatic lung deposits from synovial sarcoma of the leg is reported. Calcification within metastatic lung nodules from synovial sarcoma has not been previously reported. The differential diagnoses of calcified lung metastases are presented.", "contents": "Calcification within metastatic pulmonary nodules from synovial sarcoma. A case of calcified metastatic lung deposits from synovial sarcoma of the leg is reported. Calcification within metastatic lung nodules from synovial sarcoma has not been previously reported. The differential diagnoses of calcified lung metastases are presented."}
{"id": "PMID:214742", "title": "Calcium and sodium transport processes in patients with cystic fibrosis. I. A specific decrease in Mg2+-dependent, Ca2+-adenosine triphosphatase activity in erythrocyte membranes from cystic fibrosis patients.", "content": "Calcium-ATPase activity (Mg2+-dependent Ca2+-ATPase, ATP phosphohydrolase, EC 3.6.1.3) in erythrocyte membrane preparations from cystic fibrosis (CF) patients was greatly reduced compared to erythrocyte membranes from control subjects. The Km for calcium was found to be similar in the two groups; however, the Vmax, the maximal rate of activation of the Ca2+-ATPase, is reduced by 50% in the erythrocyte membrane preparations of the CF patients (P less than 0.001). In contrast, the Mg2+-ATPase activity of erythrocyte membranes from CF patients was unchanged compared to the control subjects. No difference in the Na+,K+-ATPase activity in erythrocyte membranes from CF patients compared to control patients could be observed. This indicates that the Ca2+-ATPase activity noted in CF erythrocytes is not part of a generalized membrane or membrane-bound enzyme alteration. It remains to be determined whether this alteration in Ca2+-ATPase activity is directly related to a defect in calcium transport in these cells and is a generalized phenomenon in CF present in cell types more directly involved in secretion.", "contents": "Calcium and sodium transport processes in patients with cystic fibrosis. I. A specific decrease in Mg2+-dependent, Ca2+-adenosine triphosphatase activity in erythrocyte membranes from cystic fibrosis patients. Calcium-ATPase activity (Mg2+-dependent Ca2+-ATPase, ATP phosphohydrolase, EC 3.6.1.3) in erythrocyte membrane preparations from cystic fibrosis (CF) patients was greatly reduced compared to erythrocyte membranes from control subjects. The Km for calcium was found to be similar in the two groups; however, the Vmax, the maximal rate of activation of the Ca2+-ATPase, is reduced by 50% in the erythrocyte membrane preparations of the CF patients (P less than 0.001). In contrast, the Mg2+-ATPase activity of erythrocyte membranes from CF patients was unchanged compared to the control subjects. No difference in the Na+,K+-ATPase activity in erythrocyte membranes from CF patients compared to control patients could be observed. This indicates that the Ca2+-ATPase activity noted in CF erythrocytes is not part of a generalized membrane or membrane-bound enzyme alteration. It remains to be determined whether this alteration in Ca2+-ATPase activity is directly related to a defect in calcium transport in these cells and is a generalized phenomenon in CF present in cell types more directly involved in secretion."}
{"id": "PMID:214743", "title": "Reye's syndrome: preservation of mitochondrial enzymes in brain and muscle compared with liver.", "content": "The activities of five mitochondrial enzymes tested in liver from patients with Reye's syndrome were measured. Citrate synthase, glutamic dehydrogenase, succinic dehydrogenase, pyruvate carboxylase, and pyruvate dehydrogenase were all outside of the range shown by control samples and well below them in activity. The activity of two extramitochondrial enzymes, glucose-6-phosphatase, which is a microsomal enzyme, and fructose-1,6-diphosphatase, which is a soluble enzyme, were in the normal range in samples from Reye's syndrome patients. In both muscle and brain the activities of the mitochondrial enzyme, citrate synthase, glutamic dehydrogenase, and succinic dehydrogenase were all within the control range. Pyruvate dehydrogenase was found to be normal in muscle from these patients.", "contents": "Reye's syndrome: preservation of mitochondrial enzymes in brain and muscle compared with liver. The activities of five mitochondrial enzymes tested in liver from patients with Reye's syndrome were measured. Citrate synthase, glutamic dehydrogenase, succinic dehydrogenase, pyruvate carboxylase, and pyruvate dehydrogenase were all outside of the range shown by control samples and well below them in activity. The activity of two extramitochondrial enzymes, glucose-6-phosphatase, which is a microsomal enzyme, and fructose-1,6-diphosphatase, which is a soluble enzyme, were in the normal range in samples from Reye's syndrome patients. In both muscle and brain the activities of the mitochondrial enzyme, citrate synthase, glutamic dehydrogenase, and succinic dehydrogenase were all within the control range. Pyruvate dehydrogenase was found to be normal in muscle from these patients."}
{"id": "PMID:214744", "title": "Serum cortisol and dehydroepiandrosterone sulfate responses to adrenocorticotropin stimulation in premature infants.", "content": "ACTH stimulation tests were performed in 15 premature infants in a serial fashion at the ages of 5--10 days and 27--31 days. Six of the 15 had subsequent ACTH stimulation tests at 6--8 weeks and/or 12--13 weeks. The pre- and post-ACTH serum cortisol and dehydroepiandrosterone sulfate (DHAS) levels were determined by radioimmunoassay. The mean basal levels of cortisol, 55 ng/ml, and DHAS, 4108 ng/ml, were significantly higher (P less than 0.05 and P less than 0.025, respectively) at 5--10 days than those of 24 ng/ml and 1858 ng/ml, respectively, at 27--31 days. The mean net change (delta) of cortisol after ACTH at 5--10 days, 95 ng/ml, increased significantly to 148 ng/ml at 27--31 days. However, deltaDHAS did not differ significantly between the two periods (1514 ng/ml vs. 972 ng/ml). Therefore, deltaDHAS/deltacortisol was lower (P less than 0.05) at 27--31 days than at 5--10 days. No further significant changes were observed after 4 weeks of age in the levels of the two steroids. There was little correlation of basal levels between cortisol and DHAS, nor between deltacortisol and deltaDHAS at any age period we studied. There were four infants whose mothers had prenatal steroid treatment for the prevention of hyaline membrane disease and their values were not different from the other infants.", "contents": "Serum cortisol and dehydroepiandrosterone sulfate responses to adrenocorticotropin stimulation in premature infants. ACTH stimulation tests were performed in 15 premature infants in a serial fashion at the ages of 5--10 days and 27--31 days. Six of the 15 had subsequent ACTH stimulation tests at 6--8 weeks and/or 12--13 weeks. The pre- and post-ACTH serum cortisol and dehydroepiandrosterone sulfate (DHAS) levels were determined by radioimmunoassay. The mean basal levels of cortisol, 55 ng/ml, and DHAS, 4108 ng/ml, were significantly higher (P less than 0.05 and P less than 0.025, respectively) at 5--10 days than those of 24 ng/ml and 1858 ng/ml, respectively, at 27--31 days. The mean net change (delta) of cortisol after ACTH at 5--10 days, 95 ng/ml, increased significantly to 148 ng/ml at 27--31 days. However, deltaDHAS did not differ significantly between the two periods (1514 ng/ml vs. 972 ng/ml). Therefore, deltaDHAS/deltacortisol was lower (P less than 0.05) at 27--31 days than at 5--10 days. No further significant changes were observed after 4 weeks of age in the levels of the two steroids. There was little correlation of basal levels between cortisol and DHAS, nor between deltacortisol and deltaDHAS at any age period we studied. There were four infants whose mothers had prenatal steroid treatment for the prevention of hyaline membrane disease and their values were not different from the other infants."}
{"id": "PMID:214751", "title": "Renin-like (angiotensinogenase) activity in human eccrine sweat.", "content": "The presence of renin or renin-like activity (RLA) was demonstrated in human eccrine sweat incubated with purified sheep angiotensinogen, using rat bioassay and angiotensin I radioimmunoassay. Following cholinergic stimulation, sweat RLA was found to range between 0 (unmeasurable) and 266 ng/ml.h, i.e. RLA-values of sweat can be about 10 times higher than those of plasma. Therefore, renin synthesis in sweat glands could be assumed. RLA following activation of beta-adrenergic receptors by the administration of isoprenaline (Aludrin) did not exceed the mean values obtained by cholinergic activation. After beta-adrenergic receptor blockade by propranolol (Dociton), RLA became unmeasurably low. Higher RLA-values were found after local injection of dibutyryl-c-AMP (90--210 ng/ml.h). The results indicate a beta-adrenergic regulation of RLA-release in human sweat glands. Human sweat glands appear to be useful for studying extrarenal renin release.", "contents": "Renin-like (angiotensinogenase) activity in human eccrine sweat. The presence of renin or renin-like activity (RLA) was demonstrated in human eccrine sweat incubated with purified sheep angiotensinogen, using rat bioassay and angiotensin I radioimmunoassay. Following cholinergic stimulation, sweat RLA was found to range between 0 (unmeasurable) and 266 ng/ml.h, i.e. RLA-values of sweat can be about 10 times higher than those of plasma. Therefore, renin synthesis in sweat glands could be assumed. RLA following activation of beta-adrenergic receptors by the administration of isoprenaline (Aludrin) did not exceed the mean values obtained by cholinergic activation. After beta-adrenergic receptor blockade by propranolol (Dociton), RLA became unmeasurably low. Higher RLA-values were found after local injection of dibutyryl-c-AMP (90--210 ng/ml.h). The results indicate a beta-adrenergic regulation of RLA-release in human sweat glands. Human sweat glands appear to be useful for studying extrarenal renin release."}
{"id": "PMID:214753", "title": "Egg-drop syndrome 76 in Danish poultry.", "content": "After a more general mention of Egg drop Syndrome 76 (EDS 76) an account is given of 3 cases of EDS 76 in broiler parent flocks. In all cases the animals involved originated from Ireland and were imported as day-olds, either directly from Ireland or via Sweden. Serological examinations indicate that the infectious agent has not previously been present in Danish hen flocks, but that it is presumably stationary in Danish flocks of ducks. In 2 of the 3 cases of EDS 76 animals from 2 different foreign firms were involved, and everything indicates that the infection has been carried by chickens from one of the firms and spread horizontally to the other. In the first case 12 weeks lapsed from the first to the last of 6 flocks in the same locality were attacked by SDS 76. An example is also given of trans-ovarial spread of EDS 76-virus to broiler flocks which at the age of 10--20 days were attacked by a disease similar to gangrenous dermatitis. In the course of the following few weeks an intensive rise took in the frequency of positive reaction to EDS 76. It is assumed that the EDS 76-virus has been of importance to the development of the said disease in these broiler flocks.", "contents": "Egg-drop syndrome 76 in Danish poultry. After a more general mention of Egg drop Syndrome 76 (EDS 76) an account is given of 3 cases of EDS 76 in broiler parent flocks. In all cases the animals involved originated from Ireland and were imported as day-olds, either directly from Ireland or via Sweden. Serological examinations indicate that the infectious agent has not previously been present in Danish hen flocks, but that it is presumably stationary in Danish flocks of ducks. In 2 of the 3 cases of EDS 76 animals from 2 different foreign firms were involved, and everything indicates that the infection has been carried by chickens from one of the firms and spread horizontally to the other. In the first case 12 weeks lapsed from the first to the last of 6 flocks in the same locality were attacked by SDS 76. An example is also given of trans-ovarial spread of EDS 76-virus to broiler flocks which at the age of 10--20 days were attacked by a disease similar to gangrenous dermatitis. In the course of the following few weeks an intensive rise took in the frequency of positive reaction to EDS 76. It is assumed that the EDS 76-virus has been of importance to the development of the said disease in these broiler flocks."}
{"id": "PMID:214754", "title": "[Marrow scintigraphy in Paget's disease of bone (author's transl)].", "content": "Marrow scintigraphy using 99mTc colloids was performed in 20 patients with Paget's disease of bone and compared with skeletal scanning in each of them. As long as the regions explored were haematopoietically active, despite the advanced age of the patients, there was decreased marrow uptake in regions of increased uptake on the skeletal scan. Whilst increased uptake of pyrophosphate reflects bone hyperosteogenesis, decreased uptake of colloids reflects marrow fibrosis, and early histological sign of the disease. This scanning technique could be a new criterion in the surveillance of the therapeutic effectiveness of calcitonins or of diphosphonates.", "contents": "[Marrow scintigraphy in Paget's disease of bone (author's transl)]. Marrow scintigraphy using 99mTc colloids was performed in 20 patients with Paget's disease of bone and compared with skeletal scanning in each of them. As long as the regions explored were haematopoietically active, despite the advanced age of the patients, there was decreased marrow uptake in regions of increased uptake on the skeletal scan. Whilst increased uptake of pyrophosphate reflects bone hyperosteogenesis, decreased uptake of colloids reflects marrow fibrosis, and early histological sign of the disease. This scanning technique could be a new criterion in the surveillance of the therapeutic effectiveness of calcitonins or of diphosphonates."}
{"id": "PMID:214756", "title": "[Epidemiology of cytomegalovirus infections (author's transl)].", "content": "Improvements of serological techniques allow seroepidemiologic surveys of cytomegalovirus infections. Intrauterine contamination is not unfrequent (1%) but pathological consequences of these infections in the fetus had only been observed after primary infections of the mother. Infections in the first days of life are frequent. The mother is almost exclusively the source of contaminations. The frequency of these infections is influenced by socio-economic factors. In adolescents and adults, contaminations seem related to closed person to person transmission (sexual behavior, kissing...).", "contents": "[Epidemiology of cytomegalovirus infections (author's transl)]. Improvements of serological techniques allow seroepidemiologic surveys of cytomegalovirus infections. Intrauterine contamination is not unfrequent (1%) but pathological consequences of these infections in the fetus had only been observed after primary infections of the mother. Infections in the first days of life are frequent. The mother is almost exclusively the source of contaminations. The frequency of these infections is influenced by socio-economic factors. In adolescents and adults, contaminations seem related to closed person to person transmission (sexual behavior, kissing...)."}
{"id": "PMID:214758", "title": "SV40 viral minichromosome: preferential exposure of the origin of replication as probed by restriction endonucleases.", "content": "Isolated SV40 minichromosomes [1-3] were treated with different single-cut restriction endonucleases to probe the arrangement of nucleosomes in relation to the SV70 DNA sequence. While Eco RI and Bam HI each cut 22-27% of the SV40 minichromosomes under limit-digest conditions, Bgl I, which cuts SV40 DNA at or very near the origin of replication [4,5], cleaves 90-95% of the minichromosomes in a preparation. Similar results were obtained with minichromosomes which had been fixed with formaldehyde before endonuclease treatment. One possible interpretation of these findings is that the arrangement of nucleosomes in the compact SV40 minichromosomes is nonrandom at least with regard to sequences near the origin of DNA replication.", "contents": "SV40 viral minichromosome: preferential exposure of the origin of replication as probed by restriction endonucleases. Isolated SV40 minichromosomes [1-3] were treated with different single-cut restriction endonucleases to probe the arrangement of nucleosomes in relation to the SV70 DNA sequence. While Eco RI and Bam HI each cut 22-27% of the SV40 minichromosomes under limit-digest conditions, Bgl I, which cuts SV40 DNA at or very near the origin of replication [4,5], cleaves 90-95% of the minichromosomes in a preparation. Similar results were obtained with minichromosomes which had been fixed with formaldehyde before endonuclease treatment. One possible interpretation of these findings is that the arrangement of nucleosomes in the compact SV40 minichromosomes is nonrandom at least with regard to sequences near the origin of DNA replication."}
{"id": "PMID:214759", "title": "The same amount of DNA is organized in in vitro-assembled nucleosomes irrespective of the origin of the histones.", "content": "The four histones H2A, H2B, H3 and H4 from calf thymus, CHO and sea urchin gastrula cells were associated by stepwise dialysis from 2 M NaCl with SV40 DNA Form I. The in vitro-assembled chromatins were visualized by electron microscopy and the size of the DNA fragments generated by digestion with DNase II was determined. Irrespective of the origin of the histones, the size of the smallest DNA band generated at early times of digestion was about 190 base pairs, whereas oligomeric DNA bands were multiples of 140 bp. These results support our previous proposal that the four histones H2A, H2B, H3 and H4 are able to organize more than 140 bp of DNA, but do not provide any evidence that the variability of histones H2A and H2B plays a role in the variability of the DNA repeat length of native chromatins.", "contents": "The same amount of DNA is organized in in vitro-assembled nucleosomes irrespective of the origin of the histones. The four histones H2A, H2B, H3 and H4 from calf thymus, CHO and sea urchin gastrula cells were associated by stepwise dialysis from 2 M NaCl with SV40 DNA Form I. The in vitro-assembled chromatins were visualized by electron microscopy and the size of the DNA fragments generated by digestion with DNase II was determined. Irrespective of the origin of the histones, the size of the smallest DNA band generated at early times of digestion was about 190 base pairs, whereas oligomeric DNA bands were multiples of 140 bp. These results support our previous proposal that the four histones H2A, H2B, H3 and H4 are able to organize more than 140 bp of DNA, but do not provide any evidence that the variability of histones H2A and H2B plays a role in the variability of the DNA repeat length of native chromatins."}
{"id": "PMID:214760", "title": "Physical properties of inner histone-DNA complexes.", "content": "Chicken-erythrocyte inner histone tetramer has been complexed with several natural and synthetic DNA duplexes by salt-gradient dialysis at various protein/DNA ratios. The resulting complexes, in low-ionic-strength buffer, have been examined by electron microscopy, circular dichroism, and thermal denaturation. Electron microscopy reveals nucleosomes (nu bodies) randomly arranged along DNA fibers, including poly(dA-dT)-poly(dA-dT), poly(dI-dC)-poly(dI-dC), but not poly(dA)-poly(dT). Circular dichroism studies showed prominent histone alpha-helix and \"suppression\" of nucleic acid ellipticity (lambda less than 240 nm). Thermal denaturation experiments revealed Tm behavior comparable to that of H1- (or H5-) depleted chromatin. Tm III and Tm IV increased linearly with G + C%(natural DNAs), but were virtually independent of the histone/DNA ratio; therefore, the melting of nucleosomes along a DNA chain is insensitive to adjacent \"spacer\" DNA lengths. This suggests that Tm III and Tm IV arise from the melting of different domains of DNA associated with the core nu body.", "contents": "Physical properties of inner histone-DNA complexes. Chicken-erythrocyte inner histone tetramer has been complexed with several natural and synthetic DNA duplexes by salt-gradient dialysis at various protein/DNA ratios. The resulting complexes, in low-ionic-strength buffer, have been examined by electron microscopy, circular dichroism, and thermal denaturation. Electron microscopy reveals nucleosomes (nu bodies) randomly arranged along DNA fibers, including poly(dA-dT)-poly(dA-dT), poly(dI-dC)-poly(dI-dC), but not poly(dA)-poly(dT). Circular dichroism studies showed prominent histone alpha-helix and \"suppression\" of nucleic acid ellipticity (lambda less than 240 nm). Thermal denaturation experiments revealed Tm behavior comparable to that of H1- (or H5-) depleted chromatin. Tm III and Tm IV increased linearly with G + C%(natural DNAs), but were virtually independent of the histone/DNA ratio; therefore, the melting of nucleosomes along a DNA chain is insensitive to adjacent \"spacer\" DNA lengths. This suggests that Tm III and Tm IV arise from the melting of different domains of DNA associated with the core nu body."}
{"id": "PMID:214761", "title": "Definition of the boundaries of the origin of DNA replication in simian virus 40.", "content": "We have determined by use of DNA sequencing techniques the exact location of the deletion in d1 892, a viable deletion mutant of Simian virus 40 (SV40) reported to map very near the unique replication origin or SV40. With the help of this localization we have narrowed down the boundaries of the replication origin to 85 nucleotides within the sequence of SV40.", "contents": "Definition of the boundaries of the origin of DNA replication in simian virus 40. We have determined by use of DNA sequencing techniques the exact location of the deletion in d1 892, a viable deletion mutant of Simian virus 40 (SV40) reported to map very near the unique replication origin or SV40. With the help of this localization we have narrowed down the boundaries of the replication origin to 85 nucleotides within the sequence of SV40."}
{"id": "PMID:214762", "title": "The turnover of tRNAs microinjected into animal cells.", "content": "Red cell-mediated microinjection has been used to study tRNA turnover in SV3T3 mouse cells and TC7 cells, an African green monkey kidney line. The turnover of endogenous tRNA, measured by labeling with 3H-methionine, was first-order with half-lives of approximately one day in SV3T3 and two days in TC7 cells. 32PtRNA isolated from E. coli or TC7 cells turned over at the same rate as endogenous tRNA when injected into either SV3T3 or TC7 cells. This demonstrates that cellular processes, not properties inherent to tRNAs, are responsible for the difference in tRNA turnover observed between SV3T3 and TC7 cells. These results further indicate that the mechanism of tRNA turnover in mammaliam cells does not distinguish prokaryotic from eukaryotic tRNAs. In contrast to unmodified tRNA, glyoxalated tRNA was rapidly degraded upon injection. Thus altered tRNA's, like altered proteins, are turned over more rapidly in animal cells.", "contents": "The turnover of tRNAs microinjected into animal cells. Red cell-mediated microinjection has been used to study tRNA turnover in SV3T3 mouse cells and TC7 cells, an African green monkey kidney line. The turnover of endogenous tRNA, measured by labeling with 3H-methionine, was first-order with half-lives of approximately one day in SV3T3 and two days in TC7 cells. 32PtRNA isolated from E. coli or TC7 cells turned over at the same rate as endogenous tRNA when injected into either SV3T3 or TC7 cells. This demonstrates that cellular processes, not properties inherent to tRNAs, are responsible for the difference in tRNA turnover observed between SV3T3 and TC7 cells. These results further indicate that the mechanism of tRNA turnover in mammaliam cells does not distinguish prokaryotic from eukaryotic tRNAs. In contrast to unmodified tRNA, glyoxalated tRNA was rapidly degraded upon injection. Thus altered tRNA's, like altered proteins, are turned over more rapidly in animal cells."}
{"id": "PMID:214763", "title": "Escherichia coli DNA topoisomerase I catalyzed linking of single-stranded rings of complementary base sequences.", "content": "Eco DNA topoisomerase I (E. coli omega protein) has been observed to catalyze the formation of double-stranded, covalently closed DNA from complementary single-stranded DNA rings, a novel reaction which is topologically forbidden without the enzyme-catalyzed breakage and rejoining of DNA backbone bonds. Incubation of a mixture of single-stranded PM2 DNA rings of complementary base sequences with omega yields a species with a sedimentation coefficient in an alkaline medium characteristic of a covalently closed circular double-stranded DNA. Buoyant density measurements in CsCl at alkaline pH also identify the product as a covalently closed duplex ring. If the omega-catalyzed reaction is stopped short of completion, highly negatively supercoiled molecules are formed which sediment more slowly in an alkaline medium than the final duplex product. As the reaction proceeds the mean sedimentation rate of the intermediates increases. This is in agreement with the expectation that the linking number between the two complementary rings increases gradually during the course of the reaction from zero to that of a relaxed covalently closed circular DNA duplex. The possible role of DNA topoisomerases in genetic recombination is discussed.", "contents": "Escherichia coli DNA topoisomerase I catalyzed linking of single-stranded rings of complementary base sequences. Eco DNA topoisomerase I (E. coli omega protein) has been observed to catalyze the formation of double-stranded, covalently closed DNA from complementary single-stranded DNA rings, a novel reaction which is topologically forbidden without the enzyme-catalyzed breakage and rejoining of DNA backbone bonds. Incubation of a mixture of single-stranded PM2 DNA rings of complementary base sequences with omega yields a species with a sedimentation coefficient in an alkaline medium characteristic of a covalently closed circular double-stranded DNA. Buoyant density measurements in CsCl at alkaline pH also identify the product as a covalently closed duplex ring. If the omega-catalyzed reaction is stopped short of completion, highly negatively supercoiled molecules are formed which sediment more slowly in an alkaline medium than the final duplex product. As the reaction proceeds the mean sedimentation rate of the intermediates increases. This is in agreement with the expectation that the linking number between the two complementary rings increases gradually during the course of the reaction from zero to that of a relaxed covalently closed circular DNA duplex. The possible role of DNA topoisomerases in genetic recombination is discussed."}
{"id": "PMID:214764", "title": "Studies on spin labeled ribonucleic acids encapsulated by viral proteins.", "content": "Spin labeled poly rA (sl-poly rA) was encapsulated by the coat proteins of two plant viruses having different morphologies: TMV, a rigid rod and CCMV, an icosahedral sphere. Electron microscopy showed that the resultant particles were morphologically similar to the parent virus from which the coat protein was obtained. Encapsulation produced progressive immobilization of the spin label. The motion of the spin label attached to TMV-sl-poly rA appears anisotropic with a correlation time about the long axis of approximately 5 x 10(-6) sec. Exogenous nuclease had no effect on the epr spectrum of this nucleo-protein complex. The epr spectrum of CCMV-sl-poly rA was isotropic with a correlation time less than 5 x 10(-7). CCMV-sl-poly rA was partially degraded by T2 ribonuclease. Theoretical calculations of correlation times for the motion of the nucleo-protein particles were similar to the experimentally derived values suggesting that the nucleo-protein particles are tightly packed with little potential for internal motion.", "contents": "Studies on spin labeled ribonucleic acids encapsulated by viral proteins. Spin labeled poly rA (sl-poly rA) was encapsulated by the coat proteins of two plant viruses having different morphologies: TMV, a rigid rod and CCMV, an icosahedral sphere. Electron microscopy showed that the resultant particles were morphologically similar to the parent virus from which the coat protein was obtained. Encapsulation produced progressive immobilization of the spin label. The motion of the spin label attached to TMV-sl-poly rA appears anisotropic with a correlation time about the long axis of approximately 5 x 10(-6) sec. Exogenous nuclease had no effect on the epr spectrum of this nucleo-protein complex. The epr spectrum of CCMV-sl-poly rA was isotropic with a correlation time less than 5 x 10(-7). CCMV-sl-poly rA was partially degraded by T2 ribonuclease. Theoretical calculations of correlation times for the motion of the nucleo-protein particles were similar to the experimentally derived values suggesting that the nucleo-protein particles are tightly packed with little potential for internal motion."}
{"id": "PMID:214765", "title": "Identification of specific fragments containing the 5' end of poliovirus RNA after ribonuclease III digestion.", "content": "The small protein (VPg) covalently linked to the 5' end of poliovirus Type 1 (PV-1) RNA has been labeled in vitro with 125I using the Bolton and Hunter reagent. The RNA is not degraded under the conditions used and nearly all the label enters VPg and not the poly-nucleotide chain. When this 125I-labeled RNA is cleaved with RNase III at low monovalent salt concentrations, one major 125I-labeled fragment, approximately 100 nucleotides long, is produced. The corresponding fragment from similar digests of 32P-labeled RNA has also been identified. The 32P-labeled fragment changes electrophoretic mobility after protease treatment indicating that it contains VPg. Furthermore, the RNase T1 oligonucleotide known to be at the 5' terminus of poliovirus RNA is found in T1 digests of the purified fragment. These results confirm that the fragment is derived from the 5' end of the RNA. This fragment will be useful in studies concerning the initiation of protein synthesis during poliovirus infection.", "contents": "Identification of specific fragments containing the 5' end of poliovirus RNA after ribonuclease III digestion. The small protein (VPg) covalently linked to the 5' end of poliovirus Type 1 (PV-1) RNA has been labeled in vitro with 125I using the Bolton and Hunter reagent. The RNA is not degraded under the conditions used and nearly all the label enters VPg and not the poly-nucleotide chain. When this 125I-labeled RNA is cleaved with RNase III at low monovalent salt concentrations, one major 125I-labeled fragment, approximately 100 nucleotides long, is produced. The corresponding fragment from similar digests of 32P-labeled RNA has also been identified. The 32P-labeled fragment changes electrophoretic mobility after protease treatment indicating that it contains VPg. Furthermore, the RNase T1 oligonucleotide known to be at the 5' terminus of poliovirus RNA is found in T1 digests of the purified fragment. These results confirm that the fragment is derived from the 5' end of the RNA. This fragment will be useful in studies concerning the initiation of protein synthesis during poliovirus infection."}
{"id": "PMID:214766", "title": "Nucleotide sequence of the leader RNA of the New Jersey serotype of vesicular stomatitis virus.", "content": "Sequence for the leader RNA Synthesized by the New Jersey serotype of vesicular stomatitis virus is presented and its complementary sequence representing the 3'-terminal sequence of the genome RNA is deduced. Comparison with the leader RNA sequence of the serologically distinct Indiana strain reveals that the 3'-terminal region of the genomes of two viruses is highly conserved.", "contents": "Nucleotide sequence of the leader RNA of the New Jersey serotype of vesicular stomatitis virus. Sequence for the leader RNA Synthesized by the New Jersey serotype of vesicular stomatitis virus is presented and its complementary sequence representing the 3'-terminal sequence of the genome RNA is deduced. Comparison with the leader RNA sequence of the serologically distinct Indiana strain reveals that the 3'-terminal region of the genomes of two viruses is highly conserved."}
{"id": "PMID:214767", "title": "Myocardial perfusion studies--direct imaging of acute myocardial injury with 99mTc-pyrophosphate.", "content": "Imaging of acute myocardial injury is possible with a large number of agents. All of these agents share similar patterns of uptake in acutely injured myocardial tissue. The technique appears to be a reliable way of ruling in or out the diagnosis of acute myocardial infarction.", "contents": "Myocardial perfusion studies--direct imaging of acute myocardial injury with 99mTc-pyrophosphate. Imaging of acute myocardial injury is possible with a large number of agents. All of these agents share similar patterns of uptake in acutely injured myocardial tissue. The technique appears to be a reliable way of ruling in or out the diagnosis of acute myocardial infarction."}
{"id": "PMID:214772", "title": "General features of persistent virus infections.", "content": "Persistent virus infections are discussed from the virus point of view in terms of the bodily sites in which the infection persists. Glands and body surfaces are thought to be significant because they give the virus protection at the topographical level from immune forces, and because they are appropriate sites for the shedding of virus to the exterior. Germ cells are relevant sites because infection can thus be transmitted vertically from generation to generation in the host. The central nervous system, however, is generally a 'dead end' from which there is no shedding to the exterior. Persistance in blood may be relevant when continued arthropod transmission becomes possible. Most persistent viruses infect lymphoreticular tissues, and this is interpreted by suggesting that it results in an impaired immune response to the infecting virus, which in turn favours persistence. It is suggested that the biological function of virus transformation and the integration of viral into host cell DNA is that it enables the infection to persist in the host and undergo reactivation. Papovaviruses, adenoviruses and oncornaviruses are considered from this point of view.", "contents": "General features of persistent virus infections. Persistent virus infections are discussed from the virus point of view in terms of the bodily sites in which the infection persists. Glands and body surfaces are thought to be significant because they give the virus protection at the topographical level from immune forces, and because they are appropriate sites for the shedding of virus to the exterior. Germ cells are relevant sites because infection can thus be transmitted vertically from generation to generation in the host. The central nervous system, however, is generally a 'dead end' from which there is no shedding to the exterior. Persistance in blood may be relevant when continued arthropod transmission becomes possible. Most persistent viruses infect lymphoreticular tissues, and this is interpreted by suggesting that it results in an impaired immune response to the infecting virus, which in turn favours persistence. It is suggested that the biological function of virus transformation and the integration of viral into host cell DNA is that it enables the infection to persist in the host and undergo reactivation. Papovaviruses, adenoviruses and oncornaviruses are considered from this point of view."}
{"id": "PMID:214774", "title": "The effect of aflatoxin B1 on the utilization of cholecalciferol by chicks.", "content": "The official A.O.A.C. (1975) vitamin D3 chick assay of bone ash was used in a study of the effect of aflatoxin B1 (AFB1) on calcification and the utilization of cholecalciferol. U.S.P. vitamin D3 reference oil (D3) was mixed into the assay diet to give 0, 50, and 100 ICU D3/kg of diet. At each level of D3, AFB1 (Calbiochem) was mixed into the diet to give concentrations of 0, .5, 1.0, 5.0, 10.0, and 20 ppm. Individual bone ash values were determined at 3 weeks of age. These bone ash values were evaluated by a multiple regression analysis for two independent variables. A highly significant regression equation demonstrated a significant interaction between AFB1 and D3 on bone calcification. The equation indicates that 1 ppm of AFB1 in the ration increases the D3 requirement of the chick by 8.84 ICU/kg of diet.", "contents": "The effect of aflatoxin B1 on the utilization of cholecalciferol by chicks. The official A.O.A.C. (1975) vitamin D3 chick assay of bone ash was used in a study of the effect of aflatoxin B1 (AFB1) on calcification and the utilization of cholecalciferol. U.S.P. vitamin D3 reference oil (D3) was mixed into the assay diet to give 0, 50, and 100 ICU D3/kg of diet. At each level of D3, AFB1 (Calbiochem) was mixed into the diet to give concentrations of 0, .5, 1.0, 5.0, 10.0, and 20 ppm. Individual bone ash values were determined at 3 weeks of age. These bone ash values were evaluated by a multiple regression analysis for two independent variables. A highly significant regression equation demonstrated a significant interaction between AFB1 and D3 on bone calcification. The equation indicates that 1 ppm of AFB1 in the ration increases the D3 requirement of the chick by 8.84 ICU/kg of diet."}
{"id": "PMID:214773", "title": "Persistence in herpes simplex virus infections.", "content": "Diseases of man caused by the virus of herpes simplex fall into two broad categories. The primary disease occurs only once in any individual's life and is caused by transmission of virus from an already infected human. Thereafter, the individual may be subject to recurrent herpetic disease, the manifestations of which are different from the primary disease. Recurrent disease varies in severity from trivial, to incapacitating and frankly lethal (as in diseases resulting from the virus's neurotropic and oncogenic properties). The source of the virus in recurrent herpetic disease has never been conclusively resolved, but is almost certainly endogenous to the patient. Theories, case reports and experiments exist to show that endogenous virus may, in periods of clinical quiescence, be latent (or persistent) at the site of the recurrent lesions itself, or more remotely in nerve tissues related to the site of recurrence.", "contents": "Persistence in herpes simplex virus infections. Diseases of man caused by the virus of herpes simplex fall into two broad categories. The primary disease occurs only once in any individual's life and is caused by transmission of virus from an already infected human. Thereafter, the individual may be subject to recurrent herpetic disease, the manifestations of which are different from the primary disease. Recurrent disease varies in severity from trivial, to incapacitating and frankly lethal (as in diseases resulting from the virus's neurotropic and oncogenic properties). The source of the virus in recurrent herpetic disease has never been conclusively resolved, but is almost certainly endogenous to the patient. Theories, case reports and experiments exist to show that endogenous virus may, in periods of clinical quiescence, be latent (or persistent) at the site of the recurrent lesions itself, or more remotely in nerve tissues related to the site of recurrence."}
{"id": "PMID:214777", "title": "[Effect of synthetic somatostatin on basal and stimulated growth hormone and prolactin secretion in vitro].", "content": "The effect of synthetic somatostatin on the basal and stimulated secretion of growth hormone and prolactin under conditions of incubation of the adenohypophysis (ADH) tissue in vitro was studied. The labeled growth hormones (GH) and prolactin (Pl) secreted was assayed by the method of electrophoresis in polyacrylamide gel as modified by the authors. Synthetic somatostatin (10 and 100 nM) suppressed the basal and stimulated by 2--0-dibutyril AMP, theophylline, and prostaglandins of E series GH labeled secretion. In doses of 100 nM the inhibitor also suppressed the basal and the stimulated by 2--0-dibutyril AMP and theophylline release of labeled Pl. Apparently, the inhibitory action of somatostatin involves the reduction of the ADH activity of adenylatecyclase.", "contents": "[Effect of synthetic somatostatin on basal and stimulated growth hormone and prolactin secretion in vitro]. The effect of synthetic somatostatin on the basal and stimulated secretion of growth hormone and prolactin under conditions of incubation of the adenohypophysis (ADH) tissue in vitro was studied. The labeled growth hormones (GH) and prolactin (Pl) secreted was assayed by the method of electrophoresis in polyacrylamide gel as modified by the authors. Synthetic somatostatin (10 and 100 nM) suppressed the basal and stimulated by 2--0-dibutyril AMP, theophylline, and prostaglandins of E series GH labeled secretion. In doses of 100 nM the inhibitor also suppressed the basal and the stimulated by 2--0-dibutyril AMP and theophylline release of labeled Pl. Apparently, the inhibitory action of somatostatin involves the reduction of the ADH activity of adenylatecyclase."}
{"id": "PMID:214781", "title": "Cyclic nucleotide-binding proteins detected by photoaffinity labeling in nucleus and cytoplasm of bovine liver.", "content": "A photoaffinity labeling method was used to characterize and compare cyclic nucleotide-binding proteins of bovine liver cytosol with binding proteins of the nucleus. After photoaffinity labeling of cytosol with 8-azido cyclic [(32)P]AMP, autoradiographs of sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed two major labeled proteins of 47,000 and 52,000-55,000 daltons. DEAE-cellulose column-derived fractions suggested that the larger protein was the regulatory subunit of peak II cyclic AMP-dependent protein kinase and the smaller protein was the regulatory subunit of peak I kinase. The smaller protein was largely present as the free regulatory subunit. The two binding proteins differed in their ability to bind cyclic GMP. Binding to both proteins was abolished by excess unlabeled cyclic AMP but not by 5'-AMP. Photoaffinity labeling of a 0.14 M salt extract of nuclei and a nonhistone chromosomal protein preparation revealed two major binding proteins with the same molecular weight and competition profiles as those of the cytosol. Detergent-washed nuclei gave similar results. Several minor binding proteins were observed in both cytosol and nucleus. One protein (36,000 daltons) was unique to the nucleus and had low affinity for 8-azido cyclic AMP. Photoaffinity labeling with cyclic [(3)H]GMP revealed a cytosol protein, absent from the nucleus, of 31,000 daltons and the ligand was competed for by both cyclic GMP and 5'-GMP. These studies suggest that the major specific cyclic AMP-binding proteins of bovine liver are the type I and type II regulatory subunits of cyclic AMP-dependent protein kinase and are present in both nucleus and cytoplasm.", "contents": "Cyclic nucleotide-binding proteins detected by photoaffinity labeling in nucleus and cytoplasm of bovine liver. A photoaffinity labeling method was used to characterize and compare cyclic nucleotide-binding proteins of bovine liver cytosol with binding proteins of the nucleus. After photoaffinity labeling of cytosol with 8-azido cyclic [(32)P]AMP, autoradiographs of sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed two major labeled proteins of 47,000 and 52,000-55,000 daltons. DEAE-cellulose column-derived fractions suggested that the larger protein was the regulatory subunit of peak II cyclic AMP-dependent protein kinase and the smaller protein was the regulatory subunit of peak I kinase. The smaller protein was largely present as the free regulatory subunit. The two binding proteins differed in their ability to bind cyclic GMP. Binding to both proteins was abolished by excess unlabeled cyclic AMP but not by 5'-AMP. Photoaffinity labeling of a 0.14 M salt extract of nuclei and a nonhistone chromosomal protein preparation revealed two major binding proteins with the same molecular weight and competition profiles as those of the cytosol. Detergent-washed nuclei gave similar results. Several minor binding proteins were observed in both cytosol and nucleus. One protein (36,000 daltons) was unique to the nucleus and had low affinity for 8-azido cyclic AMP. Photoaffinity labeling with cyclic [(3)H]GMP revealed a cytosol protein, absent from the nucleus, of 31,000 daltons and the ligand was competed for by both cyclic GMP and 5'-GMP. These studies suggest that the major specific cyclic AMP-binding proteins of bovine liver are the type I and type II regulatory subunits of cyclic AMP-dependent protein kinase and are present in both nucleus and cytoplasm."}
{"id": "PMID:214782", "title": "Formation of protein micelles from amphiphilic membrane proteins.", "content": "The membrane penicillinase (penicillin amido-beta-lactamhydrolase, EC 3.5.2.6) from Bacillus licheniformis, the Semliki Forest virus spike proteins, and the Sendai virus glycoproteins have each been isolated as soluble protein aggregates that are virtually free of lipid and detergent. The sedimentation coefficients of the complexes were 18 S, 29 S, and 43 S, respectively. Mixed aggregates containing both the virus glycoproteins and the penicillinase could also be formed. Such protein micelles may serve a number of useful purposes in membrane research.", "contents": "Formation of protein micelles from amphiphilic membrane proteins. The membrane penicillinase (penicillin amido-beta-lactamhydrolase, EC 3.5.2.6) from Bacillus licheniformis, the Semliki Forest virus spike proteins, and the Sendai virus glycoproteins have each been isolated as soluble protein aggregates that are virtually free of lipid and detergent. The sedimentation coefficients of the complexes were 18 S, 29 S, and 43 S, respectively. Mixed aggregates containing both the virus glycoproteins and the penicillinase could also be formed. Such protein micelles may serve a number of useful purposes in membrane research."}
{"id": "PMID:214779", "title": "[Participation of prostaglandins in the mechanism of hypothalamo-hypophyseal regulation of thyroid gland function].", "content": "Prostaglandins E (PGE) content was studied in the hypothalamus, hypophysis, thyroid gland and blood of rats after thyroliberin injections, thyrotropin administration, and thyroidectomy in experimental hyperthyroidism. Changes in the PGE level, cyclic adenosine monophosphate (cAMP), and in thyroxin secretion in the thyroid gland of man under the effect of thyrotropin and acetylsalicyclic acid were studied. The effect of acetylsalicylic acid on thyroxin and triiodothyronine secretion in healthy persons and those suffering from thyrotoxicosis was investigated. Analysis of the results obtained indicated that PGE played a significant role in the mechanism of the thyroid gland function regulation.", "contents": "[Participation of prostaglandins in the mechanism of hypothalamo-hypophyseal regulation of thyroid gland function]. Prostaglandins E (PGE) content was studied in the hypothalamus, hypophysis, thyroid gland and blood of rats after thyroliberin injections, thyrotropin administration, and thyroidectomy in experimental hyperthyroidism. Changes in the PGE level, cyclic adenosine monophosphate (cAMP), and in thyroxin secretion in the thyroid gland of man under the effect of thyrotropin and acetylsalicyclic acid were studied. The effect of acetylsalicylic acid on thyroxin and triiodothyronine secretion in healthy persons and those suffering from thyrotoxicosis was investigated. Analysis of the results obtained indicated that PGE played a significant role in the mechanism of the thyroid gland function regulation."}
{"id": "PMID:214783", "title": "Antipain inhibits thyroxine-induced synthesis of carbamyl phosphate synthetase I in tadpole liver.", "content": "The increased activity of carbamyl phosphate synthetase I [carbamoyl-phosphate synthase (ammonia); ATP: carbamate phosphotransferase (diphosphorylating), EC 2.7.2.5] in tadpole liver observed during thyroxine-induced metamorphosis was markedly inhibited by intraperitoneal injection of the microbial protease inhibitor antipain (0.1 micrometermol/g of body weight, twice daily). A somewhat less than maximal inhibition was seen when antipain was given only during the first 2 days of thyroxine treatment. On the other hand, little inhibition was observed when the inhibitor was given after the third or fourth day of thyroxine treatment. Antipain also inhibited thyroxine-induced increases of ornithine transcarbamylase (EC 2.1.3.3), arginase (EC 3.5.3.1), and succinate-cytochrome c reductase (EC 1.3.99.1) activities. Among other microbial protease inhibitors tested, chymostatin was nearly as effective as antipain, leupeptin was less effective, and pepstatin was ineffective. Analysis of the total liver protein and of the immunoprecipitate by sodium dodecyl sulfate/polyacrylamide gel electrophoresis showed that the inhibition was due to decreased amount of the enzyme protein. Antipain had no significant effect on leucine incorporation into total protein of tadpole liver. These results indicate the involvement of a proteolytic step in the pretranscriptional events in thyroxine-stimulated enzyme induction.", "contents": "Antipain inhibits thyroxine-induced synthesis of carbamyl phosphate synthetase I in tadpole liver. The increased activity of carbamyl phosphate synthetase I [carbamoyl-phosphate synthase (ammonia); ATP: carbamate phosphotransferase (diphosphorylating), EC 2.7.2.5] in tadpole liver observed during thyroxine-induced metamorphosis was markedly inhibited by intraperitoneal injection of the microbial protease inhibitor antipain (0.1 micrometermol/g of body weight, twice daily). A somewhat less than maximal inhibition was seen when antipain was given only during the first 2 days of thyroxine treatment. On the other hand, little inhibition was observed when the inhibitor was given after the third or fourth day of thyroxine treatment. Antipain also inhibited thyroxine-induced increases of ornithine transcarbamylase (EC 2.1.3.3), arginase (EC 3.5.3.1), and succinate-cytochrome c reductase (EC 1.3.99.1) activities. Among other microbial protease inhibitors tested, chymostatin was nearly as effective as antipain, leupeptin was less effective, and pepstatin was ineffective. Analysis of the total liver protein and of the immunoprecipitate by sodium dodecyl sulfate/polyacrylamide gel electrophoresis showed that the inhibition was due to decreased amount of the enzyme protein. Antipain had no significant effect on leucine incorporation into total protein of tadpole liver. These results indicate the involvement of a proteolytic step in the pretranscriptional events in thyroxine-stimulated enzyme induction."}
{"id": "PMID:214784", "title": "Quantitative determination of the lateral diffusion coefficients of the hormone-receptor complexes of insulin and epidermal growth factor on the plasma membrane of cultured fibroblasts.", "content": "Fluorescent derivatives of insulin and epidermal growth factor bound to 3T3 mouse fibroblasts are mobile on the cell surface, with similar diffusion coefficients, D approximately (3--5) x 10(-10) cm2/sec at 23 degrees C. Increasing the temperature to 37 degrees C results in rapid receptor immobilization. The immobilization is attributed to aggregation of hormone-receptor complexes, their internalization, or a combination of both processes.", "contents": "Quantitative determination of the lateral diffusion coefficients of the hormone-receptor complexes of insulin and epidermal growth factor on the plasma membrane of cultured fibroblasts. Fluorescent derivatives of insulin and epidermal growth factor bound to 3T3 mouse fibroblasts are mobile on the cell surface, with similar diffusion coefficients, D approximately (3--5) x 10(-10) cm2/sec at 23 degrees C. Increasing the temperature to 37 degrees C results in rapid receptor immobilization. The immobilization is attributed to aggregation of hormone-receptor complexes, their internalization, or a combination of both processes."}
{"id": "PMID:214785", "title": "Adenosine analogs inhibit adipocyte adenylate cyclase by a GTP-dependent process: basis for actions of adenosine and methylxanthines on cyclic AMP production and lipolysis.", "content": "Adenylate cyclase in purified membranes from rat adipocytes is inhibited by low concentrations of purine-modified adenosine analogs, particularly those modified in the N6 position. Such inhibition is antagonized competitively by methylxanthines, but not by other cyclic nucleotide phosphodiesterase inhibitors, and it is dependent on \"inhibitory\" concentrations of GTP in the assay medium. Ribose-modified adenosine analogs inhibit adenylate cyclase through a process that is neither dependent upon the GTP concentration nor antagonized by methylxanthines. These results explain the potent effects of adenosine and methylxanthines on fat cell metabolism and demonstrate the importance of GTP in mediating inhibition by agents that act at cell surface receptors.", "contents": "Adenosine analogs inhibit adipocyte adenylate cyclase by a GTP-dependent process: basis for actions of adenosine and methylxanthines on cyclic AMP production and lipolysis. Adenylate cyclase in purified membranes from rat adipocytes is inhibited by low concentrations of purine-modified adenosine analogs, particularly those modified in the N6 position. Such inhibition is antagonized competitively by methylxanthines, but not by other cyclic nucleotide phosphodiesterase inhibitors, and it is dependent on \"inhibitory\" concentrations of GTP in the assay medium. Ribose-modified adenosine analogs inhibit adenylate cyclase through a process that is neither dependent upon the GTP concentration nor antagonized by methylxanthines. These results explain the potent effects of adenosine and methylxanthines on fat cell metabolism and demonstrate the importance of GTP in mediating inhibition by agents that act at cell surface receptors."}
{"id": "PMID:214786", "title": "Rapid intramolecular coupling of active sites in the pyruvate dehydrogenase complex of Escherichia coli: mechanism for rate enhancement in a multimeric structure.", "content": "In the absence of CoA and presence of pyruvate, the lipoic acid residues covalently bound to the lipoate acetyltransferase core component (acetyl-CoA:dihydrolipoate S-acetyltransferase, EC 2.3.1.12) of the pyruvate dehydrogenase multienzyme complex of Escherichia coli become reductively acetylated. A study of a series of reassembled complexes varying only in their content of pyruvate decarboxylase [pyruvate:lipoate-oxidoreductase (decarboxylating and acceptor-acetylating) EC 1.2.4.1] showed that the initial direct reductive acetylation of lipoic acid residues can be followed by extensive intramolecular transacetylation reaction between lipoic acid residues on neighboring polypeptide chains of the lipoate acetyltransferase core [Bates, D. L., Danson, M. J., Hale, G., Hooper, E. A. & Perham, R. N. (1977) Nature (London) 268, 313-316]. Pulsed-quenched-flow measurements of the rates of the acetylation reactions in the various complexes now demonstrate that the intramolecular transacetylation reactions are not rate-determining in the normal reaction mechanism of the enzyme. There is therefore the potential for rapid multiple coupling of active sites in the lipoate acetyltransferase core. The rate constant for the overall complex reaction, measured by stopped-flow fluorimetry, is found to be approximately twice that for the reductive acetylation reaction measured by pulsed-quenched flow. This result could mean that CoA is an allosteric stimulator of the reductive acetylation part of the overall reaction or that there are two active sites on each chain of the lipoate acetyltransferase component working in parallel. A system of rapid functional connection of active sites in a multienzyme complex ensures that sequential reactions can be successfully coupled even under conditions of low substrate concentrations for the different steps. The substantial rate enhancement thus achieved offers a plausible explanation for the unusual complexity of the quaternary structure of the enzyme.", "contents": "Rapid intramolecular coupling of active sites in the pyruvate dehydrogenase complex of Escherichia coli: mechanism for rate enhancement in a multimeric structure. In the absence of CoA and presence of pyruvate, the lipoic acid residues covalently bound to the lipoate acetyltransferase core component (acetyl-CoA:dihydrolipoate S-acetyltransferase, EC 2.3.1.12) of the pyruvate dehydrogenase multienzyme complex of Escherichia coli become reductively acetylated. A study of a series of reassembled complexes varying only in their content of pyruvate decarboxylase [pyruvate:lipoate-oxidoreductase (decarboxylating and acceptor-acetylating) EC 1.2.4.1] showed that the initial direct reductive acetylation of lipoic acid residues can be followed by extensive intramolecular transacetylation reaction between lipoic acid residues on neighboring polypeptide chains of the lipoate acetyltransferase core [Bates, D. L., Danson, M. J., Hale, G., Hooper, E. A. & Perham, R. N. (1977) Nature (London) 268, 313-316]. Pulsed-quenched-flow measurements of the rates of the acetylation reactions in the various complexes now demonstrate that the intramolecular transacetylation reactions are not rate-determining in the normal reaction mechanism of the enzyme. There is therefore the potential for rapid multiple coupling of active sites in the lipoate acetyltransferase core. The rate constant for the overall complex reaction, measured by stopped-flow fluorimetry, is found to be approximately twice that for the reductive acetylation reaction measured by pulsed-quenched flow. This result could mean that CoA is an allosteric stimulator of the reductive acetylation part of the overall reaction or that there are two active sites on each chain of the lipoate acetyltransferase component working in parallel. A system of rapid functional connection of active sites in a multienzyme complex ensures that sequential reactions can be successfully coupled even under conditions of low substrate concentrations for the different steps. The substantial rate enhancement thus achieved offers a plausible explanation for the unusual complexity of the quaternary structure of the enzyme."}
{"id": "PMID:214787", "title": "Ca2+-dependent protein phosphorylation system in membranes from various tissues, and its activation by \"calcium-dependent regulator\".", "content": "Analysis of membranes from a variety of tissues has revealed a widespread distribution of a protein phosphorylation system dependent on the presence of both Ca2+ and \"calcium-dependent regulator\" (CDR). This protein phosphorylation system has been studied in some detail in nervous tissue. Neuronal membranes contain a protein phosphorylation system that requires Ca2+ and a soluble heat-stable protein [Schulman, H. & Greengard, P. (1978) Nature (London) 271, 478--479]. This protein has been purified to homogeneity from bovine cerebral cortex, with use of an assay based on its ability to stimulate Ca2+-dependent protein phosphorylation in membranes. This protein kinase activator appears to be identical to CDR of cyclic nucleotide phosphodiesterase. Throughout its purification, this single entity was found to activate both Ca2+-dependent protein kinase and cyclic nucleotide phosphodiesterase. The kinase activator purified here and authentic CDR were equally effective in their ability to activate Ca2+-dependent protein kinase.", "contents": "Ca2+-dependent protein phosphorylation system in membranes from various tissues, and its activation by \"calcium-dependent regulator\". Analysis of membranes from a variety of tissues has revealed a widespread distribution of a protein phosphorylation system dependent on the presence of both Ca2+ and \"calcium-dependent regulator\" (CDR). This protein phosphorylation system has been studied in some detail in nervous tissue. Neuronal membranes contain a protein phosphorylation system that requires Ca2+ and a soluble heat-stable protein [Schulman, H. & Greengard, P. (1978) Nature (London) 271, 478--479]. This protein has been purified to homogeneity from bovine cerebral cortex, with use of an assay based on its ability to stimulate Ca2+-dependent protein phosphorylation in membranes. This protein kinase activator appears to be identical to CDR of cyclic nucleotide phosphodiesterase. Throughout its purification, this single entity was found to activate both Ca2+-dependent protein kinase and cyclic nucleotide phosphodiesterase. The kinase activator purified here and authentic CDR were equally effective in their ability to activate Ca2+-dependent protein kinase."}
{"id": "PMID:214788", "title": "Sequence of oxygen binding by hemoglobin.", "content": "A nitroxide spin-label probe was attached directly to a propionic acid group of heme in either the alpha or the beta chain of hemoglobin. The electron paramagnetic resonance (EPR) spectrum of the spin label is altered by the spin-state change of the heme iron to which the spin label is attached. These hybrid hemoglobins showed normal optical and functional properties, indicating that the attachment of the spin label did not perturb the function of hemoglobin. Upon deoxygenation of alpha-heme-spin-labeled hemoglobin, EPR signals changed proportionally with oxygen saturation (determined by measuring absorption spectra). This result indicates that there is no binding preference between the alpha and beta chains of hemoglobin. However, the cross plot for the fraction of the EPR changes vs. the fraction of oxygen saturation deviated significantly from the diagonal straight line in response to the addition of 2,3-diphosphoglycerate and inositol hexaphosphate. The deviation indicated that the EPR change precedes the optical change at low oxygen tension. This result implies that, in the presence of organic phosphate, oxygen binds preferentially to the alpha subunit of deoxyhemoglobin. This conclusion was supported by the result obtained with beta-heme-spin-labeled hemoglobin: the direction of the deviation for beta-heme-spin-labeled hemoglobin in the presence of diphosphoglycerate and inositol hexaphosphate was opposite to that obtained for alpha-heme-spin-labeled hemoglobin. However, the curve deviated even in the absence of organic phosphate. This deviation for beta-heme-spin-labeled hemoglobin can be explained by the intersubunit interaction of hemoglobin. From these results, it was concluded that, in the absence of organic phosphate, oxygen combines with the alpha and beta chains with equal probability whereas, in the presence of organic phosphate, oxygen binds preferentially to the alpha chains of hemoglobin.", "contents": "Sequence of oxygen binding by hemoglobin. A nitroxide spin-label probe was attached directly to a propionic acid group of heme in either the alpha or the beta chain of hemoglobin. The electron paramagnetic resonance (EPR) spectrum of the spin label is altered by the spin-state change of the heme iron to which the spin label is attached. These hybrid hemoglobins showed normal optical and functional properties, indicating that the attachment of the spin label did not perturb the function of hemoglobin. Upon deoxygenation of alpha-heme-spin-labeled hemoglobin, EPR signals changed proportionally with oxygen saturation (determined by measuring absorption spectra). This result indicates that there is no binding preference between the alpha and beta chains of hemoglobin. However, the cross plot for the fraction of the EPR changes vs. the fraction of oxygen saturation deviated significantly from the diagonal straight line in response to the addition of 2,3-diphosphoglycerate and inositol hexaphosphate. The deviation indicated that the EPR change precedes the optical change at low oxygen tension. This result implies that, in the presence of organic phosphate, oxygen binds preferentially to the alpha subunit of deoxyhemoglobin. This conclusion was supported by the result obtained with beta-heme-spin-labeled hemoglobin: the direction of the deviation for beta-heme-spin-labeled hemoglobin in the presence of diphosphoglycerate and inositol hexaphosphate was opposite to that obtained for alpha-heme-spin-labeled hemoglobin. However, the curve deviated even in the absence of organic phosphate. This deviation for beta-heme-spin-labeled hemoglobin can be explained by the intersubunit interaction of hemoglobin. From these results, it was concluded that, in the absence of organic phosphate, oxygen combines with the alpha and beta chains with equal probability whereas, in the presence of organic phosphate, oxygen binds preferentially to the alpha chains of hemoglobin."}
{"id": "PMID:214789", "title": "Rotational motion of the sarcoplasmic reticulum Ca2+-ATPase.", "content": "Using saturation transfer electron paramagnetic resonance, we have detected the rotational motion of a spin label rigidly attached to the sarcoplasmic reticulum Ca2+-ATPase (ATP phosphohydrolase, EC 3.6.1.3). At 4 degrees C, the spectrum indicates an effective rotational correlation time of 60 microsec, determined by comparison with reference spectra obtained from theoretical calculations and from experiments on model systems. This motion appears to correspond to rotation of the enzyme with respect to the membrane, because the motion persists when the membrane fragments are immobilized by sedimentation and the motion stops when the polypeptide chains, but not the membrane vesicles, are crosslinked by glutaraldehyde. The rotational mobility of the enzyme increases with increasing temperature, and this increase becomes more gradual when the temperature exceeds 20 degrees C; the same kind of temperature dependence has been observed previously for lipid fluidity and enzymatic activity.", "contents": "Rotational motion of the sarcoplasmic reticulum Ca2+-ATPase. Using saturation transfer electron paramagnetic resonance, we have detected the rotational motion of a spin label rigidly attached to the sarcoplasmic reticulum Ca2+-ATPase (ATP phosphohydrolase, EC 3.6.1.3). At 4 degrees C, the spectrum indicates an effective rotational correlation time of 60 microsec, determined by comparison with reference spectra obtained from theoretical calculations and from experiments on model systems. This motion appears to correspond to rotation of the enzyme with respect to the membrane, because the motion persists when the membrane fragments are immobilized by sedimentation and the motion stops when the polypeptide chains, but not the membrane vesicles, are crosslinked by glutaraldehyde. The rotational mobility of the enzyme increases with increasing temperature, and this increase becomes more gradual when the temperature exceeds 20 degrees C; the same kind of temperature dependence has been observed previously for lipid fluidity and enzymatic activity."}
{"id": "PMID:214790", "title": "Induction of DNA synthesis in terminally differentiated myotubes by the activation of the src gene of Rous sarcoma virus.", "content": "Mononucleated myogenic cells from 11-day-old chicken embryos were infected with tsLA24 or tsNY68, temperature-sensitive transformation mutants of Rous sarcoma virus. The infected mononucleated myogenic cells were incubated at the nonpermissive temperature (41 degrees C) and allowed to develop into multinucleated myotubes. These myotubes have withdrawn from the cell cycle, and no DNA synthesis was observed as long as the cultures were maintained at the nonpermissive temperature. However, when the incubation temperature of these cultures was lowered to the permissive temperature (36 degrees C) for expression of the src gene, DNA synthesis was induced in multinucleated myotubes. For this induction of DNA synthesis, cells infected with tsLA24 had to be incubated at the permissive temperature for at least 50 hr, while the induction of DNA synthesis in cells infected with tsNY68 required less than 20 hr. Induction of DNA synthesis was observed by autoradiography as well as by measuring incorporation of [3H]thymidine into the macromolecule fraction in these myotube cultures. For the maintenance of capacity to induce DNA synthesis, constant presence of the src gene product is necessary, because when the temperature of these cultures was returned to 41 decrees C, the myotubes lost the capacity to induce DNA synthesis. During the process of DNA induction one biochemical marker of muscle (creatine kinase) remained unchanged.", "contents": "Induction of DNA synthesis in terminally differentiated myotubes by the activation of the src gene of Rous sarcoma virus. Mononucleated myogenic cells from 11-day-old chicken embryos were infected with tsLA24 or tsNY68, temperature-sensitive transformation mutants of Rous sarcoma virus. The infected mononucleated myogenic cells were incubated at the nonpermissive temperature (41 degrees C) and allowed to develop into multinucleated myotubes. These myotubes have withdrawn from the cell cycle, and no DNA synthesis was observed as long as the cultures were maintained at the nonpermissive temperature. However, when the incubation temperature of these cultures was lowered to the permissive temperature (36 degrees C) for expression of the src gene, DNA synthesis was induced in multinucleated myotubes. For this induction of DNA synthesis, cells infected with tsLA24 had to be incubated at the permissive temperature for at least 50 hr, while the induction of DNA synthesis in cells infected with tsNY68 required less than 20 hr. Induction of DNA synthesis was observed by autoradiography as well as by measuring incorporation of [3H]thymidine into the macromolecule fraction in these myotube cultures. For the maintenance of capacity to induce DNA synthesis, constant presence of the src gene product is necessary, because when the temperature of these cultures was returned to 41 decrees C, the myotubes lost the capacity to induce DNA synthesis. During the process of DNA induction one biochemical marker of muscle (creatine kinase) remained unchanged."}
{"id": "PMID:214791", "title": "Infectious murine leukemia virus from DNA of virus-negative AKR mouse embryo cells.", "content": "DNA from virus-negative AKR mouse embryo cells is infectious for NIH 3T3 cells if the transfected cells are treated with 5-iododeoxyuridine (IdUrd) either before or after addition of the DNA. The virus isolated after transfection of the AKR DNA is an ecotropic murine leukemia virus (MuLV) indistinguishable from endogenous AKR MuLV. The AKR DNA is not infectious in the absence of IdUrd treatment of the recipient cells. DNA from AKR cells treated with IdUrd before DNA isolation is not infectious unless the recipient cells have been treated with IdUrd. Transfected DNA from NIH mouse cells is not infectious even when the recipient cells have been treated with IdUrd. DNA from cells chronically infected with AKR MuLV or Rauscher MuLV is infectious with or without IdUrd treatment of the recipient cells, but the infectivity is not enhanced by IdUrd. The results indicate that the endogenous AKR MuLV DNA genome is potentially infectious. The data are consistent with an IdUrd-sensitive restriction in the recipient NIH 3T3 cells that prevents viral replication from endogenous AKR MuLV DNA but does not prevent viral replication from MuLV DNA of productively infected cells.", "contents": "Infectious murine leukemia virus from DNA of virus-negative AKR mouse embryo cells. DNA from virus-negative AKR mouse embryo cells is infectious for NIH 3T3 cells if the transfected cells are treated with 5-iododeoxyuridine (IdUrd) either before or after addition of the DNA. The virus isolated after transfection of the AKR DNA is an ecotropic murine leukemia virus (MuLV) indistinguishable from endogenous AKR MuLV. The AKR DNA is not infectious in the absence of IdUrd treatment of the recipient cells. DNA from AKR cells treated with IdUrd before DNA isolation is not infectious unless the recipient cells have been treated with IdUrd. Transfected DNA from NIH mouse cells is not infectious even when the recipient cells have been treated with IdUrd. DNA from cells chronically infected with AKR MuLV or Rauscher MuLV is infectious with or without IdUrd treatment of the recipient cells, but the infectivity is not enhanced by IdUrd. The results indicate that the endogenous AKR MuLV DNA genome is potentially infectious. The data are consistent with an IdUrd-sensitive restriction in the recipient NIH 3T3 cells that prevents viral replication from endogenous AKR MuLV DNA but does not prevent viral replication from MuLV DNA of productively infected cells."}
{"id": "PMID:214792", "title": "Translation of animal virus RNA in the cytoplasm of a plant cell.", "content": "Isolated Acetabularia crenulata nuclei were injected with Mengo virus RNA solution and then implanted into anucleate posterior Acetabularia mediterranea cell fragments or fused with Acetabularia ryukyuensis cytoplasts. The injected animal virus RNA was actively translated in the plant cell cytoplasm. Mengo virus proteins were detected and localized in Acetabularia cytoplasts by use of an immunofluorescence method on the first to fifth day after injection.", "contents": "Translation of animal virus RNA in the cytoplasm of a plant cell. Isolated Acetabularia crenulata nuclei were injected with Mengo virus RNA solution and then implanted into anucleate posterior Acetabularia mediterranea cell fragments or fused with Acetabularia ryukyuensis cytoplasts. The injected animal virus RNA was actively translated in the plant cell cytoplasm. Mengo virus proteins were detected and localized in Acetabularia cytoplasts by use of an immunofluorescence method on the first to fifth day after injection."}
{"id": "PMID:214793", "title": "Genetics of the large, external, transformation-sensitive (LETS) protein: assignment of a gene coding for expression of LETS to human chromosome 8.", "content": "Techniques have been developed to analyze the genetics of the large, external, transformation-sensitive (LETS) protein (fibronectin). External membrane proteins of human-mouse somatic cell hybrids with reduced numbers of human but not mouse chromosomes were labeled by lactoperoxidase-catalyzed iodination. Cell surface proteins were identified after sodium dodecyl sulfate/polyacrylamide gel electrophoresis by autoradiography of the dried gel. The LETS protein was identified in parental human cells, and LETS segregated in human-mouse cell hybrids formed from human WI-38 fibroblasts and a mouse L-cell line not expressing LETS. The LETS protein segregated concordantly with the chromosome 8 enzyme marker glutathione reductase (EC 1.6.4.2) and human chromosome 8. These findings demonstrate that a gene, LETS, encoded on chromosome 8, is responsible for the LETS protein expression in humans. Because LETS has been implicated in tumorigenicity and cellular transformation, it is of interest that rearrangement or modifications in the number of chromosome 8 have been associated with certain forms of cancer.", "contents": "Genetics of the large, external, transformation-sensitive (LETS) protein: assignment of a gene coding for expression of LETS to human chromosome 8. Techniques have been developed to analyze the genetics of the large, external, transformation-sensitive (LETS) protein (fibronectin). External membrane proteins of human-mouse somatic cell hybrids with reduced numbers of human but not mouse chromosomes were labeled by lactoperoxidase-catalyzed iodination. Cell surface proteins were identified after sodium dodecyl sulfate/polyacrylamide gel electrophoresis by autoradiography of the dried gel. The LETS protein was identified in parental human cells, and LETS segregated in human-mouse cell hybrids formed from human WI-38 fibroblasts and a mouse L-cell line not expressing LETS. The LETS protein segregated concordantly with the chromosome 8 enzyme marker glutathione reductase (EC 1.6.4.2) and human chromosome 8. These findings demonstrate that a gene, LETS, encoded on chromosome 8, is responsible for the LETS protein expression in humans. Because LETS has been implicated in tumorigenicity and cellular transformation, it is of interest that rearrangement or modifications in the number of chromosome 8 have been associated with certain forms of cancer."}
{"id": "PMID:214794", "title": "Human antibodies reactive with purified envelope antigens of primate type C tumor viruses.", "content": "Human sera from healthy individuals have been shown to react with viral antigens in preparations of detergent-disrupted C type viruses from monkeys. In this report, it is demonstrated that (populations of) these human antibodies react with highly purified envelope glycoproteins of the simian sarcoma virus-simian sarcoma-associated virus complex and the Friend leukemia virus complex. Several immunological parameters influencing human antibody binding to C type tumor virus antigens have been characterized. These parameters indicate that human antibodies tend to bind to what is probably a subset of the antigenic determinants on the virus envelope antigens and that different human sera recognize the same antigenic determinants on the virus envelope antigens tested. The possible origin of these antibodies is discussed.", "contents": "Human antibodies reactive with purified envelope antigens of primate type C tumor viruses. Human sera from healthy individuals have been shown to react with viral antigens in preparations of detergent-disrupted C type viruses from monkeys. In this report, it is demonstrated that (populations of) these human antibodies react with highly purified envelope glycoproteins of the simian sarcoma virus-simian sarcoma-associated virus complex and the Friend leukemia virus complex. Several immunological parameters influencing human antibody binding to C type tumor virus antigens have been characterized. These parameters indicate that human antibodies tend to bind to what is probably a subset of the antigenic determinants on the virus envelope antigens and that different human sera recognize the same antigenic determinants on the virus envelope antigens tested. The possible origin of these antibodies is discussed."}
{"id": "PMID:214795", "title": "Reversal of renovascular hypertension by antibodies specific for angiotensin-converting enzyme.", "content": "Goat antibodies developed against pure rabbit pulmonary angiotensin-converting enzyme (peptidyl dipeptidase, EC 3.4.15.1) were administered intravenously to rats with two-kidney Goldblatt hypertension and to normotensive animals. In the hypertensive model these antibodies were associated with a sustained, immune-dependent decrease of blood pressure to normal values. A smaller, but also immune-specific, reduction of blood pressure was observed in the normotensive group. The data suggest that heterologous antibody directed against angiotensin-converting enzyme may provide a biologically specific probe for examining the contribution of the renin-angiotensin system to normal and pathologic circulatory states.", "contents": "Reversal of renovascular hypertension by antibodies specific for angiotensin-converting enzyme. Goat antibodies developed against pure rabbit pulmonary angiotensin-converting enzyme (peptidyl dipeptidase, EC 3.4.15.1) were administered intravenously to rats with two-kidney Goldblatt hypertension and to normotensive animals. In the hypertensive model these antibodies were associated with a sustained, immune-dependent decrease of blood pressure to normal values. A smaller, but also immune-specific, reduction of blood pressure was observed in the normotensive group. The data suggest that heterologous antibody directed against angiotensin-converting enzyme may provide a biologically specific probe for examining the contribution of the renin-angiotensin system to normal and pathologic circulatory states."}
{"id": "PMID:214796", "title": "Isolation of host-range variants of mouse mammary tumor viruses that efficiently infect cells in vitro.", "content": "Host-range variants of mouse mammary tumor virus (MMTV) have been isolated that have the ability to productively infect cells in vitro with high efficiency (at multiplicities of infection </=1) and with extremely short latent periods to the production of de novo virus (as short as 4 days after infection). These variants of the highly oncogenic MMTV of RIII, C3H, and GR mice were obtained by serial virus passage in feline cells. The resultant variant stocks react in group-specific radioimmunoassays for the MMTV major external glycoprotein (gp52) and major internal protein (p28), possess a protein profile similar to that of wild-type MMTV, and contain a virion-associated DNA polymerase with a magnesium cation preference. Addition of dexamethasone and insulin to culture media enhances the titer of de novo MMTV to levels of approximately 10(10) particles per 75-cm(2) flask (containing 5 x 10(6) cells) per 24 hr. Variant stocks exhibit no evidence of contamination with either murine or feline type C retroviruses, as assayed by various techniques. The variants of MMTV derived from C3H and RIII mice exhibit differential host ranges that include the ability to productively infect feline, canine, bat, mink, murine, and human cells. Use of these MMTV host-range variants now facilitates the study of the complete replicative cycle of MMTV as well as an elucidation of the interaction of MMTV with various hormones, physical or chemical carcinogens, and tumor promoters in the initiation and promotion of mammary neoplasia.", "contents": "Isolation of host-range variants of mouse mammary tumor viruses that efficiently infect cells in vitro. Host-range variants of mouse mammary tumor virus (MMTV) have been isolated that have the ability to productively infect cells in vitro with high efficiency (at multiplicities of infection </=1) and with extremely short latent periods to the production of de novo virus (as short as 4 days after infection). These variants of the highly oncogenic MMTV of RIII, C3H, and GR mice were obtained by serial virus passage in feline cells. The resultant variant stocks react in group-specific radioimmunoassays for the MMTV major external glycoprotein (gp52) and major internal protein (p28), possess a protein profile similar to that of wild-type MMTV, and contain a virion-associated DNA polymerase with a magnesium cation preference. Addition of dexamethasone and insulin to culture media enhances the titer of de novo MMTV to levels of approximately 10(10) particles per 75-cm(2) flask (containing 5 x 10(6) cells) per 24 hr. Variant stocks exhibit no evidence of contamination with either murine or feline type C retroviruses, as assayed by various techniques. The variants of MMTV derived from C3H and RIII mice exhibit differential host ranges that include the ability to productively infect feline, canine, bat, mink, murine, and human cells. Use of these MMTV host-range variants now facilitates the study of the complete replicative cycle of MMTV as well as an elucidation of the interaction of MMTV with various hormones, physical or chemical carcinogens, and tumor promoters in the initiation and promotion of mammary neoplasia."}
{"id": "PMID:214801", "title": "Electron reactions with cytochrome c in ethylene glycol/water glass at-196 degrees C.", "content": "Low temperature gamma-irradiation and spectroscopy are used to study electron reactions with cytochrome c in aquo organic glass at-196 degrees C. Spectral data suggests that cytochrome c is reduced by electron at 196 degrees C. Raising the glass temperature reveals further changes in spectrum, suggesting that conformational changes may occur in cytochrome c molecule during stabilization of reductive process.", "contents": "Electron reactions with cytochrome c in ethylene glycol/water glass at-196 degrees C. Low temperature gamma-irradiation and spectroscopy are used to study electron reactions with cytochrome c in aquo organic glass at-196 degrees C. Spectral data suggests that cytochrome c is reduced by electron at 196 degrees C. Raising the glass temperature reveals further changes in spectrum, suggesting that conformational changes may occur in cytochrome c molecule during stabilization of reductive process."}
{"id": "PMID:214803", "title": "Effects of inhibition of prostaglandin-synthesis on renal electrolyte excretion and concentrating ability in healthy man.", "content": "In five healthy subjects inhibition of prostaglandin (PG)-synthesis with indomethacin did not significantly alter glomerular filtration, urinary flow rate or sodium and potassium excretion during control urine collection periods or i.v. hypertonic saline infusion. Saline administration was accompanied by a fall in urinary PGEI-excretion from 0.58 +/- 0.14 to 0.26 +/- 0.09 ng/min (p less than 0.05). While indomethacin had no effect on basal urinary osmolality (Uosm), renal concentrating ability following hypertonic saline or i.v. administration of 100 mU lysine-vasopressin significantly increased in the presence of indomethacin with Uosm rising from 805 +/- 25 to 970 +/- 53 mosm/L (p less than 0.01) and from 839 +/- 47 to 996 +/- 62 mosm/L (p less than 0.01), resp. Since this was not accompanied by respective changes in urinary excretion of cyclic adenosine monophosphate (cAMP) mechanisms other than PG-antagonism of vasopressin, such as decreased medullary washout of solute, may contribute to enhanced renal concentrating ability following inhibition of PG-synthesis with indomethacin.", "contents": "Effects of inhibition of prostaglandin-synthesis on renal electrolyte excretion and concentrating ability in healthy man. In five healthy subjects inhibition of prostaglandin (PG)-synthesis with indomethacin did not significantly alter glomerular filtration, urinary flow rate or sodium and potassium excretion during control urine collection periods or i.v. hypertonic saline infusion. Saline administration was accompanied by a fall in urinary PGEI-excretion from 0.58 +/- 0.14 to 0.26 +/- 0.09 ng/min (p less than 0.05). While indomethacin had no effect on basal urinary osmolality (Uosm), renal concentrating ability following hypertonic saline or i.v. administration of 100 mU lysine-vasopressin significantly increased in the presence of indomethacin with Uosm rising from 805 +/- 25 to 970 +/- 53 mosm/L (p less than 0.01) and from 839 +/- 47 to 996 +/- 62 mosm/L (p less than 0.01), resp. Since this was not accompanied by respective changes in urinary excretion of cyclic adenosine monophosphate (cAMP) mechanisms other than PG-antagonism of vasopressin, such as decreased medullary washout of solute, may contribute to enhanced renal concentrating ability following inhibition of PG-synthesis with indomethacin."}
{"id": "PMID:214808", "title": "Who becomes chronic?", "content": "Chronic social disablement is caused by three types of factor: impairment, e.g. slowness in schizophrenia; social disadvantage, e.g. lack of opportunity to develop social or vocational skills; and an underconfidence or unduly low self-esteem which is reactive to impairment and disadvantage. The last of these factors is particularly evident in 'institutionalism', a condition in which the individual comes to acquire a contentment with institutional life and wishes to lead no other. Many long-stay patients in large mental hospitals used to be 'well-institutionalized' but it became recognized that retraining and rehabilitation could lead to successful resettlement outside hospital. For a time these striking successes suggested to some theorists that abolishing the hospitals would abolish disablement as well but it is now quite clear that this is not the case. Chronic impairments still occur and create a continuing need for sheltered environments. The frequency and type of problems still arising are discussed in the light of recent surveys in England. One small group requires highly-staffed accommodation, others need less supervised day and residential settings; all need long-term care. It is emphasized that some people living at home with relatives also have chronic mental disabilities as have a high proportion of the destitute. Such problems are less frequent than formerly but they still require detailed medical and social attention.", "contents": "Who becomes chronic? Chronic social disablement is caused by three types of factor: impairment, e.g. slowness in schizophrenia; social disadvantage, e.g. lack of opportunity to develop social or vocational skills; and an underconfidence or unduly low self-esteem which is reactive to impairment and disadvantage. The last of these factors is particularly evident in 'institutionalism', a condition in which the individual comes to acquire a contentment with institutional life and wishes to lead no other. Many long-stay patients in large mental hospitals used to be 'well-institutionalized' but it became recognized that retraining and rehabilitation could lead to successful resettlement outside hospital. For a time these striking successes suggested to some theorists that abolishing the hospitals would abolish disablement as well but it is now quite clear that this is not the case. Chronic impairments still occur and create a continuing need for sheltered environments. The frequency and type of problems still arising are discussed in the light of recent surveys in England. One small group requires highly-staffed accommodation, others need less supervised day and residential settings; all need long-term care. It is emphasized that some people living at home with relatives also have chronic mental disabilities as have a high proportion of the destitute. Such problems are less frequent than formerly but they still require detailed medical and social attention."}
{"id": "PMID:214809", "title": "When schizophrenia comes marching home.", "content": "Deinstitutionalization of the chronically mentally ill has only recently been recognized as a phenomenon which may not be in the best interests of the patients involved. The reasons for this include the lack of adequate community-based resources for domiciliary, treatment, and rehabilitative services, plus the response of society to deviant behavior. However, the most fundamental problem is likely to be the severity of the illnesses with which we are concerned, so that the solution cannot be as simple as the sending \"home\" of the long-term patients. Prevention of institutionalization is seen as a more feasible goal than its cure. This requires a comprehensive program incorporating, among other things, a recognition of the necessary role of the mental hospital, and the need to improve the quality of care provided therein.", "contents": "When schizophrenia comes marching home. Deinstitutionalization of the chronically mentally ill has only recently been recognized as a phenomenon which may not be in the best interests of the patients involved. The reasons for this include the lack of adequate community-based resources for domiciliary, treatment, and rehabilitative services, plus the response of society to deviant behavior. However, the most fundamental problem is likely to be the severity of the illnesses with which we are concerned, so that the solution cannot be as simple as the sending \"home\" of the long-term patients. Prevention of institutionalization is seen as a more feasible goal than its cure. This requires a comprehensive program incorporating, among other things, a recognition of the necessary role of the mental hospital, and the need to improve the quality of care provided therein."}
{"id": "PMID:214814", "title": "Bile duct obstruction in hepatocellular carcinoma (hepatoma)--clinical and cholangiographic characteristics. Report of 6 cases and review of the literature.", "content": "Direct cholangiography revealed 6 cases of hepatoma where tumor growth within the bile ducts caused obstructive jaundice. Characteristic features included bulky obstructing intraluminal masses in the proximal extrahepatic ducts. Distal common duct defects usually signify hemobilia and clots as tumor complication. Review of the literature disclosed only 22 cases in which common duct involvement was a predominant clinical feature. Hepatoma should be included in the different diagnosis of a cholangiographic filling defect in the proximal extrahepatic bile ducts. The recent widespread use of endoscopic and fine needle transhepatic cholangiography should aid in preoperative diagnosis.", "contents": "Bile duct obstruction in hepatocellular carcinoma (hepatoma)--clinical and cholangiographic characteristics. Report of 6 cases and review of the literature. Direct cholangiography revealed 6 cases of hepatoma where tumor growth within the bile ducts caused obstructive jaundice. Characteristic features included bulky obstructing intraluminal masses in the proximal extrahepatic ducts. Distal common duct defects usually signify hemobilia and clots as tumor complication. Review of the literature disclosed only 22 cases in which common duct involvement was a predominant clinical feature. Hepatoma should be included in the different diagnosis of a cholangiographic filling defect in the proximal extrahepatic bile ducts. The recent widespread use of endoscopic and fine needle transhepatic cholangiography should aid in preoperative diagnosis."}
{"id": "PMID:214822", "title": "Experimental hyperthyroidism in rats suppresses in vitro prostaglandin metabolism in lung and kidney.", "content": "Metabolism of prostaglandin (PG) F2alpha and PGE2 was depressed 40--62% in 100,000 g cytoplasmic supernatants of lungs and kidneys prepared from rats made hyperthyroid by 18 daily L(-) thyroxine injections (200microgram, s--c). These hyperthyroid rats had elevated serum thyroxine levels, cardiac hypertrophy and thyroid atrophy. There were no differences in soluble protein concentrations, NAD+ utilisation by endogenous enzymes and substrates, or in the NAD+ dependence of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) between the supernatants prepared from hyperthyroid rats and saline-injected controls. Thyroxine did not inhibit PG metabolism in vitro up to 260 micrometer. These results suggest that thyroxine specifically decreases intracellular levels of PG-metabolising enzymes, especially of the rate-limiting 15-PGDH. Metabolism of PGF2alpha and PGE2 by 15-PGDH was faster in smaller rats and declined with increasing animal weight. These studies imply that some of the clinical features of hyperthyroidism in man might be caused by deficiencies in PG metabolism.", "contents": "Experimental hyperthyroidism in rats suppresses in vitro prostaglandin metabolism in lung and kidney. Metabolism of prostaglandin (PG) F2alpha and PGE2 was depressed 40--62% in 100,000 g cytoplasmic supernatants of lungs and kidneys prepared from rats made hyperthyroid by 18 daily L(-) thyroxine injections (200microgram, s--c). These hyperthyroid rats had elevated serum thyroxine levels, cardiac hypertrophy and thyroid atrophy. There were no differences in soluble protein concentrations, NAD+ utilisation by endogenous enzymes and substrates, or in the NAD+ dependence of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) between the supernatants prepared from hyperthyroid rats and saline-injected controls. Thyroxine did not inhibit PG metabolism in vitro up to 260 micrometer. These results suggest that thyroxine specifically decreases intracellular levels of PG-metabolising enzymes, especially of the rate-limiting 15-PGDH. Metabolism of PGF2alpha and PGE2 by 15-PGDH was faster in smaller rats and declined with increasing animal weight. These studies imply that some of the clinical features of hyperthyroidism in man might be caused by deficiencies in PG metabolism."}
{"id": "PMID:214823", "title": "Stimulatory effect of prostaglandins on the production of hexosamine-containing substances by cultured fibroblasts (4) adenosine 3':5'-cyclic monophosphate independent stimulation by prostaglandin F2alpha.", "content": "The mechanism of the stimulatory effect of prostaglandin PG) F2alpha on the production of hexosamine-containing substances by cultured fibroblasts was studied with special reference to adenosine 3':5'-cyclic monophosphate (cAMP). At the stationary phase, the cells were exposed for 6 hrs to PGF2alpha, E1, cAMP or dibutyryl-cAMP in a wide range of concentrations. cAMP itself showed a slight stimulation on the production of hexosamine-containing substances, and the effect was enhanced by using the dibutyryl derivative. PGF2alpha had much a greater capacity than either the exogeneous cAMP or the dibutyryl-cAMP for enhancing the production of hexosamine-containing substances. To know whether cAMP is involved in the stimulatory effect of PGF2alpha, intracellular cAMP level was concomitantly measured in both PGF2alpha and PGE1 treated cultures. Although the cellular cAMP level in PGE1 treated cultures was much higher than that in the PGF2alpha treated cultures, the stimulatory effect on the production of hexosamine-containing substances in PGE1 treated cultures was always much smaller than that in the PGF2alpha treated cultures. Moreover, PGF2alpha had a significant stimulatory effect on the production of hexosamine-containing substances even at a low concentration as 100 pg/ml, which is small enough not to increase any cellular cAMP level. From these results, it was concluded that the stimulatory effect of PGF2alpha on the production of hexosamine-containing substances by cultured fibroblasts is not mediated by cAMP and is caused by a mechanism different from that caused by cAMP.", "contents": "Stimulatory effect of prostaglandins on the production of hexosamine-containing substances by cultured fibroblasts (4) adenosine 3':5'-cyclic monophosphate independent stimulation by prostaglandin F2alpha. The mechanism of the stimulatory effect of prostaglandin PG) F2alpha on the production of hexosamine-containing substances by cultured fibroblasts was studied with special reference to adenosine 3':5'-cyclic monophosphate (cAMP). At the stationary phase, the cells were exposed for 6 hrs to PGF2alpha, E1, cAMP or dibutyryl-cAMP in a wide range of concentrations. cAMP itself showed a slight stimulation on the production of hexosamine-containing substances, and the effect was enhanced by using the dibutyryl derivative. PGF2alpha had much a greater capacity than either the exogeneous cAMP or the dibutyryl-cAMP for enhancing the production of hexosamine-containing substances. To know whether cAMP is involved in the stimulatory effect of PGF2alpha, intracellular cAMP level was concomitantly measured in both PGF2alpha and PGE1 treated cultures. Although the cellular cAMP level in PGE1 treated cultures was much higher than that in the PGF2alpha treated cultures, the stimulatory effect on the production of hexosamine-containing substances in PGE1 treated cultures was always much smaller than that in the PGF2alpha treated cultures. Moreover, PGF2alpha had a significant stimulatory effect on the production of hexosamine-containing substances even at a low concentration as 100 pg/ml, which is small enough not to increase any cellular cAMP level. From these results, it was concluded that the stimulatory effect of PGF2alpha on the production of hexosamine-containing substances by cultured fibroblasts is not mediated by cAMP and is caused by a mechanism different from that caused by cAMP."}
{"id": "PMID:214824", "title": "Prostacyclin: a potent stimulator of adrenal steroidogenesis.", "content": "The relative potencies of various prostaglandins were investigated in trypsin-dispersed cat adrenocortical cells. Prostacyclin proved to be the most potent steroidogenic prostaglandin, being 100-1000 times more potent than PGE2. This stimulant effect of prostacyclin was only partially dependent upon the presence of extracellular calcium and was associated with increased levels of cyclic AMP. These data suggest a possible role for prostacyclin in corticosteroidogenesis.", "contents": "Prostacyclin: a potent stimulator of adrenal steroidogenesis. The relative potencies of various prostaglandins were investigated in trypsin-dispersed cat adrenocortical cells. Prostacyclin proved to be the most potent steroidogenic prostaglandin, being 100-1000 times more potent than PGE2. This stimulant effect of prostacyclin was only partially dependent upon the presence of extracellular calcium and was associated with increased levels of cyclic AMP. These data suggest a possible role for prostacyclin in corticosteroidogenesis."}
{"id": "PMID:214831", "title": "Development of tolerance to the ACTH-releasing effects of beta-endorphin.", "content": "Acute intracisternal injection of human beta-endorphin results in increased plasma concentration of adrenocorticotropic hormone (ACTH). Repeated injections of beta-endorphin are associated with the development of tolerance with regard to this ACTH-stimulating effect.", "contents": "Development of tolerance to the ACTH-releasing effects of beta-endorphin. Acute intracisternal injection of human beta-endorphin results in increased plasma concentration of adrenocorticotropic hormone (ACTH). Repeated injections of beta-endorphin are associated with the development of tolerance with regard to this ACTH-stimulating effect."}
{"id": "PMID:214832", "title": "Crystalline cytoplasmic inclusions in the liver cells of two mongrel dogs.", "content": "Crystalline inclusions were found in the cytoplasmic matrix of the liver cells in 2 out of 5 healthy mongrel dogs. The crystals were rectangular, with fine granular structure and free from the surrounding membrane. Their appearance was different from the intramitochondrial crystalline inclusions described in human and dog livers, as well as from those observed in the livers of other species. The significance of this unique finding remains unclear, but it is suggested that these inclusions represent crystalized protein.", "contents": "Crystalline cytoplasmic inclusions in the liver cells of two mongrel dogs. Crystalline inclusions were found in the cytoplasmic matrix of the liver cells in 2 out of 5 healthy mongrel dogs. The crystals were rectangular, with fine granular structure and free from the surrounding membrane. Their appearance was different from the intramitochondrial crystalline inclusions described in human and dog livers, as well as from those observed in the livers of other species. The significance of this unique finding remains unclear, but it is suggested that these inclusions represent crystalized protein."}
{"id": "PMID:214833", "title": "Induction of chicken interferon by avian infectious bronchitis virus.", "content": "The ability of nine strains of avian infectious bronchitis virus (IBV) to induce chicken interferon has been investigated using Semliki Forest virus for the tests. The Beaudette, H120 and Connecticut 46 strains induced interferon in the allantoic fluids of embryonated hens' eggs, the highest titre (1 : 30) being associated with Beaudette; but these as well as the Massachusetts M-41 and H52 strains failed to yield interferon in primary monolayer cultures of chick kidney cells as did all nine strains in organ cultures of chick embryo trachea. None of six strains of IBV investigated was susceptible to the inhibitory effects of chicken interferon.", "contents": "Induction of chicken interferon by avian infectious bronchitis virus. The ability of nine strains of avian infectious bronchitis virus (IBV) to induce chicken interferon has been investigated using Semliki Forest virus for the tests. The Beaudette, H120 and Connecticut 46 strains induced interferon in the allantoic fluids of embryonated hens' eggs, the highest titre (1 : 30) being associated with Beaudette; but these as well as the Massachusetts M-41 and H52 strains failed to yield interferon in primary monolayer cultures of chick kidney cells as did all nine strains in organ cultures of chick embryo trachea. None of six strains of IBV investigated was susceptible to the inhibitory effects of chicken interferon."}
{"id": "PMID:214834", "title": "Parainfluenza-3 virus: difference in capacity of neuraminidase-weak and strong strains to infect young calves and to elicit cellular immune response.", "content": "Calves less than four weeks old could not be infected with a neuraminidase-weak strain of parainfluenza-3 virus (Pi3) but were successfully infected with either of two neuraminidase-strong strains. The criteria for infection were virus excretion, cell-mediated and antibody-mediated immune responses. In the lymphocyte stimulation test, calves infected with the neuraminidase-strong Pi3 strain T\u00fcb-E6 responded more strongly to antigen prepared from this strain than to antigen from the heterologous Pi3 strain Um-23. The non-immunoglobulin haemagglutination inhibition activity of the liquid phase of nasal secretions of newborn calves decreased after treatment with Vibrio cholerae neuraminidase. For virus-bound neuraminidase the liquid phase from newborn calves was a richer substrate than the liquid phase from older animals.", "contents": "Parainfluenza-3 virus: difference in capacity of neuraminidase-weak and strong strains to infect young calves and to elicit cellular immune response. Calves less than four weeks old could not be infected with a neuraminidase-weak strain of parainfluenza-3 virus (Pi3) but were successfully infected with either of two neuraminidase-strong strains. The criteria for infection were virus excretion, cell-mediated and antibody-mediated immune responses. In the lymphocyte stimulation test, calves infected with the neuraminidase-strong Pi3 strain T\u00fcb-E6 responded more strongly to antigen prepared from this strain than to antigen from the heterologous Pi3 strain Um-23. The non-immunoglobulin haemagglutination inhibition activity of the liquid phase of nasal secretions of newborn calves decreased after treatment with Vibrio cholerae neuraminidase. For virus-bound neuraminidase the liquid phase from newborn calves was a richer substrate than the liquid phase from older animals."}
{"id": "PMID:214835", "title": "The distribution of antibodies to Border disease virus among sheep in England and Wales.", "content": "Within a sample of the sheep population of England and Wales, 10.8 per cent of 3506 individuals had immunodiffusion test antibody to bovine viral diarrhoea mucosal disease virus antigen. There were marked differences between various geographical regions in the proportion of sheep with antibody, and Border disease may be more common in some areas than disease records indicate.", "contents": "The distribution of antibodies to Border disease virus among sheep in England and Wales. Within a sample of the sheep population of England and Wales, 10.8 per cent of 3506 individuals had immunodiffusion test antibody to bovine viral diarrhoea mucosal disease virus antigen. There were marked differences between various geographical regions in the proportion of sheep with antibody, and Border disease may be more common in some areas than disease records indicate."}
{"id": "PMID:214836", "title": "Effects of swab materials and transport media on Aujeszky's disease virus.", "content": "The effect of swab materials on the recovery of Aujeszky's disease virus from various transport media held at 4 degrees C was investigated over a five day period. No significant loss in infectivity was found in control preparations, approximately 50 per cent of infectivity was recovered from fluids containing applicator wire and approximately 10 per cent from fluids containing polyester fibre or cotton wool. Virus recovery from fluids containing wooden applicator sticks ranged from no virus recovery in protein free media to from 1 to 10 per cent in protein containing media. Freezing followed by thawing was the most effective of the physical methods used for eluting virus from swab materials.", "contents": "Effects of swab materials and transport media on Aujeszky's disease virus. The effect of swab materials on the recovery of Aujeszky's disease virus from various transport media held at 4 degrees C was investigated over a five day period. No significant loss in infectivity was found in control preparations, approximately 50 per cent of infectivity was recovered from fluids containing applicator wire and approximately 10 per cent from fluids containing polyester fibre or cotton wool. Virus recovery from fluids containing wooden applicator sticks ranged from no virus recovery in protein free media to from 1 to 10 per cent in protein containing media. Freezing followed by thawing was the most effective of the physical methods used for eluting virus from swab materials."}
{"id": "PMID:214838", "title": "[Fisher's syndrome. Peripheral or central origin (author's transl)].", "content": "The syndrome described by M. Fisher in 1956 includes ophtalmoplegia, ataxia, and generalized loss of reflexes. It is classically considered to be of peripheral origin and its relation to Guillain and Barre's syndrome in its mesencephalic form is debatable. The authors review 5 cases and discuss the question of a probable central origin. They base their opinion on the pathognomonic features of these cases and those in the literature, as well as the results of their oculographic and electromyographic studies. They stress the importance of the nature of the ataxia; the severe equilibrium disturbances noted in these patients could result, contrary to usual thinking, more from a central vestibular syndrome than from a cerebellar lesion.", "contents": "[Fisher's syndrome. Peripheral or central origin (author's transl)]. The syndrome described by M. Fisher in 1956 includes ophtalmoplegia, ataxia, and generalized loss of reflexes. It is classically considered to be of peripheral origin and its relation to Guillain and Barre's syndrome in its mesencephalic form is debatable. The authors review 5 cases and discuss the question of a probable central origin. They base their opinion on the pathognomonic features of these cases and those in the literature, as well as the results of their oculographic and electromyographic studies. They stress the importance of the nature of the ataxia; the severe equilibrium disturbances noted in these patients could result, contrary to usual thinking, more from a central vestibular syndrome than from a cerebellar lesion."}
{"id": "PMID:214841", "title": "The pharmacology of phagocytosis.", "content": "The biochemical mechanisms underlying the processes of chemotaxis, adhesion, phagocytosis and lysosomal enzyme secretion are described. Particular attention is drawn to the roles of aerobic glycolysis, the hexose monophosphate shunt, cyclic adenosine monophosphate, cyclic guanosine monophosphate and the microtubular and microfilament systems. The way in which drugs modify these pathways is discussed with reference to agonists and antagonists of beta-receptors, agonist and antagonists of muscarinic receptors, prostaglandins, colchicine, Cytochalasin B, and to steroidal and non-steroidal anti-inflammatory agents. The possibility that anti-inflammatory agents produce a significant effect in this manner is considered.", "contents": "The pharmacology of phagocytosis. The biochemical mechanisms underlying the processes of chemotaxis, adhesion, phagocytosis and lysosomal enzyme secretion are described. Particular attention is drawn to the roles of aerobic glycolysis, the hexose monophosphate shunt, cyclic adenosine monophosphate, cyclic guanosine monophosphate and the microtubular and microfilament systems. The way in which drugs modify these pathways is discussed with reference to agonists and antagonists of beta-receptors, agonist and antagonists of muscarinic receptors, prostaglandins, colchicine, Cytochalasin B, and to steroidal and non-steroidal anti-inflammatory agents. The possibility that anti-inflammatory agents produce a significant effect in this manner is considered."}
{"id": "PMID:214846", "title": "Dental maturity in hypopituitarism, and dental response to substitution treatment.", "content": "In 25 patients with hypopituitarism the relation of skeletal and dental maturity and the effects on it of substitution therapy for 2-4 years were analyzed. Dental age was retarded less regularly and to a lesser degree than skeletal age and statural growth. In most patients dental age was within the range of 0-2 s.d. All components of dental development seemed equally retarded. Changes in dental delay during GH treatment were variable, but in most cases parallel to the changes in statural and skeletal delay. When treatment was discontinued the lag in dental age increased, showing a response similar to that of skeletal age.", "contents": "Dental maturity in hypopituitarism, and dental response to substitution treatment. In 25 patients with hypopituitarism the relation of skeletal and dental maturity and the effects on it of substitution therapy for 2-4 years were analyzed. Dental age was retarded less regularly and to a lesser degree than skeletal age and statural growth. In most patients dental age was within the range of 0-2 s.d. All components of dental development seemed equally retarded. Changes in dental delay during GH treatment were variable, but in most cases parallel to the changes in statural and skeletal delay. When treatment was discontinued the lag in dental age increased, showing a response similar to that of skeletal age."}
{"id": "PMID:214847", "title": "Erythrocytosis and Wilms' tumour.", "content": "A Wilms' tumour was diagnosed in an 18-year-old male patient with erythrocytosis. After radical excision of the tumour and postoperative irradiation and chemotherapy, the erythrocytosis disappeared and did not recur during a 2-year observation period. The levels of erythropoiesis-stimulating activity in serum and in the renal mass suggest the tumour as the source of this activity. The rarity of the association is discussed and a review of the literature is given.", "contents": "Erythrocytosis and Wilms' tumour. A Wilms' tumour was diagnosed in an 18-year-old male patient with erythrocytosis. After radical excision of the tumour and postoperative irradiation and chemotherapy, the erythrocytosis disappeared and did not recur during a 2-year observation period. The levels of erythropoiesis-stimulating activity in serum and in the renal mass suggest the tumour as the source of this activity. The rarity of the association is discussed and a review of the literature is given."}
{"id": "PMID:214849", "title": "Illnesses during the first two years of life and their association with perinatal cytomegalovirus infection.", "content": "In order to find out whether perinatal cytomegalovirus (CMV) infection causes clinical symptoms or signs or influences the general morbidity of a child, a prospective study was performed on 147 children during their first year of life. 48 infants were infected with CMV perinatally. Reports of clinical infections during the second year were available from a total of 108 infants, and serum samples for viral antibody screening at the age 24 months from 111. No specific symptoms or signs could be attributed to perinatal CMV infection. None of the symptoms previously described in connection with CMV infection in childhood were observed. Urinary tract infections were, however, noticed in the group of perinatally infected children. Judging from the prevalence of illnesses and the frequency of elevated antibody titres against different agents, perinatal CMV infection does not seem to influence the general morbidity of a child. In general, the frequency and distribution of illnesses were the same as previously reported by Finnish authors. Breast-feeding did not protect against infection. The children of CMV seronegative mothers were not resistant to other infections, although all of them escaped perinatal CMV infection.", "contents": "Illnesses during the first two years of life and their association with perinatal cytomegalovirus infection. In order to find out whether perinatal cytomegalovirus (CMV) infection causes clinical symptoms or signs or influences the general morbidity of a child, a prospective study was performed on 147 children during their first year of life. 48 infants were infected with CMV perinatally. Reports of clinical infections during the second year were available from a total of 108 infants, and serum samples for viral antibody screening at the age 24 months from 111. No specific symptoms or signs could be attributed to perinatal CMV infection. None of the symptoms previously described in connection with CMV infection in childhood were observed. Urinary tract infections were, however, noticed in the group of perinatally infected children. Judging from the prevalence of illnesses and the frequency of elevated antibody titres against different agents, perinatal CMV infection does not seem to influence the general morbidity of a child. In general, the frequency and distribution of illnesses were the same as previously reported by Finnish authors. Breast-feeding did not protect against infection. The children of CMV seronegative mothers were not resistant to other infections, although all of them escaped perinatal CMV infection."}
{"id": "PMID:214845", "title": "[Importance of numeric scintigraphy of the hips during primary aseptic osteonecrosis of the femoral head in adults].", "content": "The authors have studied 58 cases of primitive aseptic osteonecrosis of the hips, 35 cases of coxarthrosis, 12 algodystrophies and 11 cases of coxitis, using numerical scintigraphy with Technetium 99m pyrophosphate. They have studied the ration of uptake by the femoral head over the uptake by the soft issues. The values obtained are compared to those observed in the study of normal hips. The result is that the technique offers the possibility of establishing, in a more differential manner, a diagnosis of lesion of the hips at an infraradiologic stage.", "contents": "[Importance of numeric scintigraphy of the hips during primary aseptic osteonecrosis of the femoral head in adults]. The authors have studied 58 cases of primitive aseptic osteonecrosis of the hips, 35 cases of coxarthrosis, 12 algodystrophies and 11 cases of coxitis, using numerical scintigraphy with Technetium 99m pyrophosphate. They have studied the ration of uptake by the femoral head over the uptake by the soft issues. The values obtained are compared to those observed in the study of normal hips. The result is that the technique offers the possibility of establishing, in a more differential manner, a diagnosis of lesion of the hips at an infraradiologic stage."}
{"id": "PMID:214850", "title": "Rotavirus infections in families. A clinical and virological study.", "content": "Among 25 family members of 8 children with acute rotavirus gastroenteritis (8 siblings and 17 adults) gastroenteritis was recorded in 9 (5 siblings and 4 adults), and minor symptoms in 8 (2 siblings and 6 adults). A rotavirus infection was diagnosed in 7 of the family members with gastroenteritis and was probably the cause of the disease in the remaining 2 in this group. Four of the 8 family members with minor symptoms were infected with rotavirus, whereas no infection was detected among the 8 family members without symptoms. Serological findings sugggested that infants and young children underwent a primary infection with rotavirus, whereas older children and adults probably were reinfected. Adults as well as children with rotavirus infection excreted virus and may have served as sources of infection.", "contents": "Rotavirus infections in families. A clinical and virological study. Among 25 family members of 8 children with acute rotavirus gastroenteritis (8 siblings and 17 adults) gastroenteritis was recorded in 9 (5 siblings and 4 adults), and minor symptoms in 8 (2 siblings and 6 adults). A rotavirus infection was diagnosed in 7 of the family members with gastroenteritis and was probably the cause of the disease in the remaining 2 in this group. Four of the 8 family members with minor symptoms were infected with rotavirus, whereas no infection was detected among the 8 family members without symptoms. Serological findings sugggested that infants and young children underwent a primary infection with rotavirus, whereas older children and adults probably were reinfected. Adults as well as children with rotavirus infection excreted virus and may have served as sources of infection."}
{"id": "PMID:214851", "title": "The effect of alpha-adrenergic stimulation in stress incontinence.", "content": "The urethra is innervated by adrenergic fibres and its smooth muscle is equipped mainly with alpha-adrenoreceptors. Norephedrine chloride, which is an alpha-stimulating agent, has been proposed as therapy for stress incontinence, since it was shown to increase the maximum urethral pressure at rest. For further study of the effect of norephedrine chloride on the urethal closure pressure at rest and in a dynamic situation, we examined ten severely stress-incontinent women before and after three weeks of treatment with this agent (100 mg by mouth twice daily). The urethral closure pressure at rest, between coughs of varied strength and at the precise moment of stress were recorded. The margin to leakage, the tone of the urethral wall and the transmission of pressure from abdomen to urethra were also among the estimated factors. No improvement was found in any of these respects. Alpha stimulation in this form therefore seems ineffective in severe stress incontinence and is not an alternative to surgical treatment.", "contents": "The effect of alpha-adrenergic stimulation in stress incontinence. The urethra is innervated by adrenergic fibres and its smooth muscle is equipped mainly with alpha-adrenoreceptors. Norephedrine chloride, which is an alpha-stimulating agent, has been proposed as therapy for stress incontinence, since it was shown to increase the maximum urethral pressure at rest. For further study of the effect of norephedrine chloride on the urethal closure pressure at rest and in a dynamic situation, we examined ten severely stress-incontinent women before and after three weeks of treatment with this agent (100 mg by mouth twice daily). The urethral closure pressure at rest, between coughs of varied strength and at the precise moment of stress were recorded. The margin to leakage, the tone of the urethral wall and the transmission of pressure from abdomen to urethra were also among the estimated factors. No improvement was found in any of these respects. Alpha stimulation in this form therefore seems ineffective in severe stress incontinence and is not an alternative to surgical treatment."}
{"id": "PMID:214852", "title": "The pineal gland: a biological clock in vitro.", "content": "Circadian rhythmicity was studied by following the course of N-acetyl-transferase activity in the pineal glands of chickens in vitro. The results indicate (i) a daily change during day 1 of organ culture in constant dark that was dependent on the time the chickens were killed, (ii) equivocal persistence of the daily change in constant dark during 6 to 7 days of organ culture, (iii) an effect of light, (iv) inhibition by adrenergic agents and cycloheximide, and (v) stimulation by dibutyryl adenosine 3',5'-monophosphate and related compounds.", "contents": "The pineal gland: a biological clock in vitro. Circadian rhythmicity was studied by following the course of N-acetyl-transferase activity in the pineal glands of chickens in vitro. The results indicate (i) a daily change during day 1 of organ culture in constant dark that was dependent on the time the chickens were killed, (ii) equivocal persistence of the daily change in constant dark during 6 to 7 days of organ culture, (iii) an effect of light, (iv) inhibition by adrenergic agents and cycloheximide, and (v) stimulation by dibutyryl adenosine 3',5'-monophosphate and related compounds."}
{"id": "PMID:214853", "title": "Nicotinamide adenine dinucleotide splitting enzyme: a characteristic of the mouse macrophage.", "content": "Murine macrophages are endowed with nicotinamide adenine dinucleotide splitting activity that is markedly higher than that of other cells, tissues, or organs of the mouse. This enzyme therefore can be used as a biochemical marker for distinguishing macrophages from other cells of the lymphoreticular system and from polymorphonuclear leukocytes.", "contents": "Nicotinamide adenine dinucleotide splitting enzyme: a characteristic of the mouse macrophage. Murine macrophages are endowed with nicotinamide adenine dinucleotide splitting activity that is markedly higher than that of other cells, tissues, or organs of the mouse. This enzyme therefore can be used as a biochemical marker for distinguishing macrophages from other cells of the lymphoreticular system and from polymorphonuclear leukocytes."}
{"id": "PMID:214854", "title": "Cellular analysis of long-term habituation of the gill-withdrawal reflex of Aplysia californica.", "content": "Long-term habituation training in Aplysia californica produces a profound depression in the efficacy of synaptic transmission between mechanoreceptor neurons and gill motor neurons. This depression persists for more than 3 weeks. Thus a critical synaptic site for plasticity underlying long-term habituation is the same as that for short-term habituation. For this simple form of learning, short- and long-term memory share a common locus and aspects of a common mechanism: synaptic depression.", "contents": "Cellular analysis of long-term habituation of the gill-withdrawal reflex of Aplysia californica. Long-term habituation training in Aplysia californica produces a profound depression in the efficacy of synaptic transmission between mechanoreceptor neurons and gill motor neurons. This depression persists for more than 3 weeks. Thus a critical synaptic site for plasticity underlying long-term habituation is the same as that for short-term habituation. For this simple form of learning, short- and long-term memory share a common locus and aspects of a common mechanism: synaptic depression."}
{"id": "PMID:214855", "title": "Synaptic phosphoproteins: specific changes after repetitive stimulation of the hippocampal slice.", "content": "Repetitive stimulation (100 pulses per second for 1 second) of the Schafer collateral-commissural system of the rat hippocampus induces long-term potentiation of synaptic strength and produces significant changes in the subsequent endogenous phosphorylation of a 40,000-dalton protein from synaptic plasma membranes. This effect is not observed after stimulation in calcium-deficient media or after simulation at the rate of one pulse per second for 100 seconds. These findings provide evidence that repetitive synaptic activation can alter the phosphorylation machinery of the synaptic region and suggest a biochemical process which may be involved in the production of neuronal plasticity.", "contents": "Synaptic phosphoproteins: specific changes after repetitive stimulation of the hippocampal slice. Repetitive stimulation (100 pulses per second for 1 second) of the Schafer collateral-commissural system of the rat hippocampus induces long-term potentiation of synaptic strength and produces significant changes in the subsequent endogenous phosphorylation of a 40,000-dalton protein from synaptic plasma membranes. This effect is not observed after stimulation in calcium-deficient media or after simulation at the rate of one pulse per second for 100 seconds. These findings provide evidence that repetitive synaptic activation can alter the phosphorylation machinery of the synaptic region and suggest a biochemical process which may be involved in the production of neuronal plasticity."}
{"id": "PMID:214856", "title": "Octopamine receptors, adenosine 3',5'-monophosphate, and neural control of firefly flashing.", "content": "An adenylate cyclase activated as much as 25-fold by low concentrations of octopamine has been identified in the firefly lantern. The relative potency of octopamine and various other amines in stimulating this enzyme, and effects of antagonists in blocking octopamine activation, correlate well with the known effects of these agents in affecting light production. In addition to suggesting a role for adenosine 3',5'-monophosphate (or pyrophosphate) in the neural control of firefly flashing, identification of this potent enzyme should facilitate the characterization of phenylethylamine receptors in excitable tissue.", "contents": "Octopamine receptors, adenosine 3',5'-monophosphate, and neural control of firefly flashing. An adenylate cyclase activated as much as 25-fold by low concentrations of octopamine has been identified in the firefly lantern. The relative potency of octopamine and various other amines in stimulating this enzyme, and effects of antagonists in blocking octopamine activation, correlate well with the known effects of these agents in affecting light production. In addition to suggesting a role for adenosine 3',5'-monophosphate (or pyrophosphate) in the neural control of firefly flashing, identification of this potent enzyme should facilitate the characterization of phenylethylamine receptors in excitable tissue."}
{"id": "PMID:214857", "title": "[Acute leukemia and primary Vaquez' polycythemia. 20 cases].", "content": "The authors report the clinical and hematological course of 20 patients with polycythemia vera complicated by acute leukemia. This was responsible for 35,8% of the 53 deaths in the series of 103 patients treated with radioactive phosphorus. It occurred on average 12 years after the first treatment. The data in these cases are compared with those in the literature. The role of ionising radiation and/or the myelo-proliferative syndrome itself in the onset of acute leukemia is discussed.", "contents": "[Acute leukemia and primary Vaquez' polycythemia. 20 cases]. The authors report the clinical and hematological course of 20 patients with polycythemia vera complicated by acute leukemia. This was responsible for 35,8% of the 53 deaths in the series of 103 patients treated with radioactive phosphorus. It occurred on average 12 years after the first treatment. The data in these cases are compared with those in the literature. The role of ionising radiation and/or the myelo-proliferative syndrome itself in the onset of acute leukemia is discussed."}
{"id": "PMID:214858", "title": "[Evans' syndrome during acute myelomonocytic leukemia. 2 cases].", "content": "The immune abnormalities observed during acute myeloblastic leukemia often remain undiagnosed for they generally have no practical consequences. The association of peripheral thrombopenia and a positive direct Coomb's test, during two cases of acute myelo-monocytic leukemia should be recognised owing to the difficulty of interpretation and the therapeutic consequences.", "contents": "[Evans' syndrome during acute myelomonocytic leukemia. 2 cases]. The immune abnormalities observed during acute myeloblastic leukemia often remain undiagnosed for they generally have no practical consequences. The association of peripheral thrombopenia and a positive direct Coomb's test, during two cases of acute myelo-monocytic leukemia should be recognised owing to the difficulty of interpretation and the therapeutic consequences."}
{"id": "PMID:214859", "title": "[Multiple myeloma and acute leukemia. Simultaneous evolution of plasmacyte and myelomonocytic clones].", "content": "The authors report two cases of acute myelo-monocytic leukemia occuring during the course of multiple myeloma treated by local radiotherapy and melphalan. Both patients underwent a complete remission of their myeloma for 27 and 78 months. The myeloma relapsed suddenly in the form of an acute leukemia. In one case, the onset of acute leukemia was preceded by a syndrome of marrow failure with numerous crown-shaped sideroblasts and an excess of myeloblasts in the marrow. This stage lasted two years. The biochemical abnormalities of the red cells usually associated with refractory anemia and preleukemic conditions were present in the other case.", "contents": "[Multiple myeloma and acute leukemia. Simultaneous evolution of plasmacyte and myelomonocytic clones]. The authors report two cases of acute myelo-monocytic leukemia occuring during the course of multiple myeloma treated by local radiotherapy and melphalan. Both patients underwent a complete remission of their myeloma for 27 and 78 months. The myeloma relapsed suddenly in the form of an acute leukemia. In one case, the onset of acute leukemia was preceded by a syndrome of marrow failure with numerous crown-shaped sideroblasts and an excess of myeloblasts in the marrow. This stage lasted two years. The biochemical abnormalities of the red cells usually associated with refractory anemia and preleukemic conditions were present in the other case."}
{"id": "PMID:214861", "title": "[Extramedullary lymphosarcoma, erythroblastopenia and gastric adenocarcinoma. Apropos of a case].", "content": "The authors report the case of a patient with lymphosarcoma and erythroblastopenia who died following a surgical operation for gastric carcinoma. The erythroblastopenia, corrected by radiotherapy of the lymphosarcoma, reappeared during the relapse. The link between these two diseases seems undoubted. The later appearance of a gastric carcinoma suggested the predisposing role of the first neoplasm, and/or its treatment, through an immunological disorder.", "contents": "[Extramedullary lymphosarcoma, erythroblastopenia and gastric adenocarcinoma. Apropos of a case]. The authors report the case of a patient with lymphosarcoma and erythroblastopenia who died following a surgical operation for gastric carcinoma. The erythroblastopenia, corrected by radiotherapy of the lymphosarcoma, reappeared during the relapse. The link between these two diseases seems undoubted. The later appearance of a gastric carcinoma suggested the predisposing role of the first neoplasm, and/or its treatment, through an immunological disorder."}
{"id": "PMID:214863", "title": "[Collagen : physiological approach to skin healing,. Its application to the practical treatment of leg ulcers (author's transl)].", "content": "Collagen gel has been studied, during a comparative trial, as a topic for cicatrization on a series of twenty patients with severe leg ulcers rebellious to the usual methods of treatment. A complete healing was obtained in 16 cases out of 20, after a period of 8 to 60 days. Collafilm Gel must only be applied to clean, uninfected wounds. It's action seems noticeable by the appearance of network cicatrization, the mechanism and signification of which is being discussed by the authors.", "contents": "[Collagen : physiological approach to skin healing,. Its application to the practical treatment of leg ulcers (author's transl)]. Collagen gel has been studied, during a comparative trial, as a topic for cicatrization on a series of twenty patients with severe leg ulcers rebellious to the usual methods of treatment. A complete healing was obtained in 16 cases out of 20, after a period of 8 to 60 days. Collafilm Gel must only be applied to clean, uninfected wounds. It's action seems noticeable by the appearance of network cicatrization, the mechanism and signification of which is being discussed by the authors."}
{"id": "PMID:214864", "title": "[Radiological signs of tumours of the adrenal glands (author's transl)].", "content": "The authors discuss the radiological signs in 18 patients with an adrenal tumour. 7 of them had a Cushing's syndrome, 10 others a phaechromocytoma and the last had primary hyperaldosteronism. The diagnosis was made from the history, the clinical picture, hormone estimations and pharmacodynamic tests, whilts in the majority of cases the tumour was localised by radiodiagnosis. In all cases, there was hypertension, permanent in tumours of the adrenal cortex, paroxysmal or permanent in the cases of pheochromocytomas. We emphasise the importance of retro-pneumoperitoneum, as the radiological investigation of choice, in the localisation of adrenal tumours, especially pheochromocytomas, and in Cushing's syndrome. In cases of pheochromocytoma, one should follow carefully the blood pressure, during special radiological investigations, in view of the danger of a sudden rise or fall in blood pressure, the first is treated with phentolamine, the second with noradrenaline solution. Finally, a scan using I 131 19-iodocholesterol may be valuable in diagnosis and localisation of adrenal tumours; it has in particular given very encouraging results in the differential diagnosis of adrenal tumours with the clinical presentation of Cushing's disease.", "contents": "[Radiological signs of tumours of the adrenal glands (author's transl)]. The authors discuss the radiological signs in 18 patients with an adrenal tumour. 7 of them had a Cushing's syndrome, 10 others a phaechromocytoma and the last had primary hyperaldosteronism. The diagnosis was made from the history, the clinical picture, hormone estimations and pharmacodynamic tests, whilts in the majority of cases the tumour was localised by radiodiagnosis. In all cases, there was hypertension, permanent in tumours of the adrenal cortex, paroxysmal or permanent in the cases of pheochromocytomas. We emphasise the importance of retro-pneumoperitoneum, as the radiological investigation of choice, in the localisation of adrenal tumours, especially pheochromocytomas, and in Cushing's syndrome. In cases of pheochromocytoma, one should follow carefully the blood pressure, during special radiological investigations, in view of the danger of a sudden rise or fall in blood pressure, the first is treated with phentolamine, the second with noradrenaline solution. Finally, a scan using I 131 19-iodocholesterol may be valuable in diagnosis and localisation of adrenal tumours; it has in particular given very encouraging results in the differential diagnosis of adrenal tumours with the clinical presentation of Cushing's disease."}
{"id": "PMID:214862", "title": "[The importance of quantitative left ventriculography in coronary heart disease (author's transl)].", "content": "Regional impairment of left ventricular contraction in chronic stage of coronary artery disease is best demonstrated by using left ventriculography. Moreover, left ventricular volumes and ejection fraction can be computed from this angiography. Changes in these volumetric parameters are closely related to the degree of left ventricular dysfonction and to the adaptation mechanisms due to ventricular asynergy. Since left ventricular dysfonction has a high prognostic value in coronary artery disease (CAD), left ventricular volumes and ejection fraction should be measured as a routine of angiographic evaluation of CAD.", "contents": "[The importance of quantitative left ventriculography in coronary heart disease (author's transl)]. Regional impairment of left ventricular contraction in chronic stage of coronary artery disease is best demonstrated by using left ventriculography. Moreover, left ventricular volumes and ejection fraction can be computed from this angiography. Changes in these volumetric parameters are closely related to the degree of left ventricular dysfonction and to the adaptation mechanisms due to ventricular asynergy. Since left ventricular dysfonction has a high prognostic value in coronary artery disease (CAD), left ventricular volumes and ejection fraction should be measured as a routine of angiographic evaluation of CAD."}
{"id": "PMID:214865", "title": "[The failures of surgery in peptic ulcer. Report of 62 reoperations (author's transl)].", "content": "62 reoperations were performed in 54 patients for failure of surgery for chronic ulcer. In 15 cases there was a recurrence of an ulcer left in position, in 32 cases there was an anastomotic ulcer, in 4 cases, severe hemorrhage for severe inflammation of the stoma without recurrence of the ulcer and in 11 cases, there were severe functional disorders. The authors are convinced that in the treatment of recurrent ulcer, vagotomy should always complete gastrectomy and vice versa. It is because they did not follow this advice in the early stages that they had to reoperate certain patients several times for new ulcer recurrences. The results of reoperation for functional disorders when indicated in a gastrectomised patient were mediocre in the vagotomised patients.", "contents": "[The failures of surgery in peptic ulcer. Report of 62 reoperations (author's transl)]. 62 reoperations were performed in 54 patients for failure of surgery for chronic ulcer. In 15 cases there was a recurrence of an ulcer left in position, in 32 cases there was an anastomotic ulcer, in 4 cases, severe hemorrhage for severe inflammation of the stoma without recurrence of the ulcer and in 11 cases, there were severe functional disorders. The authors are convinced that in the treatment of recurrent ulcer, vagotomy should always complete gastrectomy and vice versa. It is because they did not follow this advice in the early stages that they had to reoperate certain patients several times for new ulcer recurrences. The results of reoperation for functional disorders when indicated in a gastrectomised patient were mediocre in the vagotomised patients."}
{"id": "PMID:214866", "title": "[Effect of sustained release alprenolol in hypertension uncontrolled by chlorothiazide and dihydralazine. Study in double blind (author's transl)].", "content": "In 20 hypertensive patients with functioning renal graft, sustained release alprenolol or placebo was given orally for 2 months, in combination with chlorothiazide and dihydralazine, after previous failure of these 2 last drugs. Blood pressure was normalized with alprenolol during the length of the study, but is was not with placebo. Mean plasma renine level decreased of 45 p. cent.", "contents": "[Effect of sustained release alprenolol in hypertension uncontrolled by chlorothiazide and dihydralazine. Study in double blind (author's transl)]. In 20 hypertensive patients with functioning renal graft, sustained release alprenolol or placebo was given orally for 2 months, in combination with chlorothiazide and dihydralazine, after previous failure of these 2 last drugs. Blood pressure was normalized with alprenolol during the length of the study, but is was not with placebo. Mean plasma renine level decreased of 45 p. cent."}
{"id": "PMID:214869", "title": "[A new treatment of Huntington's chorea. Report of three cases (author's transl)].", "content": "The authors report their experience in three cases of Huntington's chorea treated with tiapride (Tiapridal). A real efficacy and an interesting effect of the drug were observed on choreic hyperkinesias. No regression of the other symptoms were noted and the course of the disease not changed.", "contents": "[A new treatment of Huntington's chorea. Report of three cases (author's transl)]. The authors report their experience in three cases of Huntington's chorea treated with tiapride (Tiapridal). A real efficacy and an interesting effect of the drug were observed on choreic hyperkinesias. No regression of the other symptoms were noted and the course of the disease not changed."}
{"id": "PMID:214874", "title": "Hepatic carcinoma with opisthorchiasis.", "content": "Eighty-seven cases of primary hepatic carcinoma associated with opisthorchiasis were reviewed. The prevalence of liver carcinoma among 154 cases of liver fluke infection was 56.6%. The tumours were classified histologically as cholangiocarcinoma in 67 cases (77%), hepatocellular carcinoma in 9 (10.3%), mixed hepatocholangiocarcinoma in 4, squamous carcinoma in 2, and undifferentiated carcinoma in 5. Metastases, found in 71 cases, occurred most frequently in the regional lymph nodes and lungs. There were numerous or moderate numbers of liver flukes in most of these cases.", "contents": "Hepatic carcinoma with opisthorchiasis. Eighty-seven cases of primary hepatic carcinoma associated with opisthorchiasis were reviewed. The prevalence of liver carcinoma among 154 cases of liver fluke infection was 56.6%. The tumours were classified histologically as cholangiocarcinoma in 67 cases (77%), hepatocellular carcinoma in 9 (10.3%), mixed hepatocholangiocarcinoma in 4, squamous carcinoma in 2, and undifferentiated carcinoma in 5. Metastases, found in 71 cases, occurred most frequently in the regional lymph nodes and lungs. There were numerous or moderate numbers of liver flukes in most of these cases."}
{"id": "PMID:214870", "title": "[Neopergonal treatment in male hypogonadotropic hypogonadism (author's transl)].", "content": "Male hypogonadotropic hypogonadism is a rare disease but a caracteristic one of currently isolated gonadotropin deficiency. 15 subjects have been treated during 6 to 52 monthes with Neopergonal (225 UI a week) + H.C.G. (15 00 IU a week). We observed spermatogenesis onset in 11 patients, sufficient 9 of them, poor in 2 others.", "contents": "[Neopergonal treatment in male hypogonadotropic hypogonadism (author's transl)]. Male hypogonadotropic hypogonadism is a rare disease but a caracteristic one of currently isolated gonadotropin deficiency. 15 subjects have been treated during 6 to 52 monthes with Neopergonal (225 UI a week) + H.C.G. (15 00 IU a week). We observed spermatogenesis onset in 11 patients, sufficient 9 of them, poor in 2 others."}
{"id": "PMID:214867", "title": "[Risk factors in aorto-iliac surgery (author's transl)].", "content": "The authors report a statistical analysis of 163 operations of aorto-iliac vascular surgery. A detailed study of their 14 deaths showed the various causes of mortality (immediate post-operative thrombosis, acute renal failure, digestive complications, septic cardiac, pulmonary, hemorrhagic and cerebro-vascular accidents). This analysis, compared with the findings in all the operated patients showed the main factors of risk in this type of surgery (age over 70 years immediate and late reoperations, heart lesions, renal, pulmonary and late lesions, the risk of sepsis). The indicate the means of prevention of such accidents and the therapeutic attitude when they occur. They conclude that the contra-indications are relative, but should be observed in order to lower the risk of this surgery below 5 p. cent mortality rate.", "contents": "[Risk factors in aorto-iliac surgery (author's transl)]. The authors report a statistical analysis of 163 operations of aorto-iliac vascular surgery. A detailed study of their 14 deaths showed the various causes of mortality (immediate post-operative thrombosis, acute renal failure, digestive complications, septic cardiac, pulmonary, hemorrhagic and cerebro-vascular accidents). This analysis, compared with the findings in all the operated patients showed the main factors of risk in this type of surgery (age over 70 years immediate and late reoperations, heart lesions, renal, pulmonary and late lesions, the risk of sepsis). The indicate the means of prevention of such accidents and the therapeutic attitude when they occur. They conclude that the contra-indications are relative, but should be observed in order to lower the risk of this surgery below 5 p. cent mortality rate."}
{"id": "PMID:214872", "title": "[Eosinophilic pleurisy. Apropos of 35 cases].", "content": "Eosinophilic pleuritis are inflammatory effusions containing more than 10% of eosinocytes. More frequent in men, the course of illness is acute our subacute but pleural sequelae are seldom. They can be due to all inflammatory process, thoracic trauma, tuberculosis and viral diseases are predominant. Unexplained etiology represents 25% of cases, so \"called autonomous pleuritis\". Pleural eosinophilia could be explained by eosinophilotactic action of red cells or by activating products induced during hypersensibility reaction.", "contents": "[Eosinophilic pleurisy. Apropos of 35 cases]. Eosinophilic pleuritis are inflammatory effusions containing more than 10% of eosinocytes. More frequent in men, the course of illness is acute our subacute but pleural sequelae are seldom. They can be due to all inflammatory process, thoracic trauma, tuberculosis and viral diseases are predominant. Unexplained etiology represents 25% of cases, so \"called autonomous pleuritis\". Pleural eosinophilia could be explained by eosinophilotactic action of red cells or by activating products induced during hypersensibility reaction."}
{"id": "PMID:214876", "title": "Selective and reconstructive surgical procedures for carcinoma of the breast.", "content": "Eighteen hundred and fifty-nine patients with primary carcinoma of the breast from New York Medical College-Flower and Fifth Avenue Hospitals were treated by a moderate selective surgical approach between 1950 and 1975. Seven hundred and eleven patients with potentially curable carcinoma of the breast were observed for ten or more years. Based upon strict criteria of evaluation, the series did not have an increased number of prognostically favorable cancers compared with that of other series. The results obtained were most rewarding regarding absolute gross ten year survival rates, local recurrence rates, percentage of skin grafts, management of the other breast, arm and shoulder function and cosmetic appearance, especially in relation to reconstruction of the breast in properly selected patients.", "contents": "Selective and reconstructive surgical procedures for carcinoma of the breast. Eighteen hundred and fifty-nine patients with primary carcinoma of the breast from New York Medical College-Flower and Fifth Avenue Hospitals were treated by a moderate selective surgical approach between 1950 and 1975. Seven hundred and eleven patients with potentially curable carcinoma of the breast were observed for ten or more years. Based upon strict criteria of evaluation, the series did not have an increased number of prognostically favorable cancers compared with that of other series. The results obtained were most rewarding regarding absolute gross ten year survival rates, local recurrence rates, percentage of skin grafts, management of the other breast, arm and shoulder function and cosmetic appearance, especially in relation to reconstruction of the breast in properly selected patients."}
{"id": "PMID:214877", "title": "Small hemorrhages vs. small calcifications in brain tumors: difficulty in differentiation by computed tomography.", "content": "The difficulty in differentiating multiple small hemorrhages from multiple small calcifications in brain tumors by computed tomography (CT) is discussed. Illustrative CT scans are presented and the theoretical basis for this problem is elaborated. The difficulty is attributed to the relatively large size of the voxel and the ensuing partial volume effect, particularly with small intraparenchymal lesions of different sizes and attenuations.", "contents": "Small hemorrhages vs. small calcifications in brain tumors: difficulty in differentiation by computed tomography. The difficulty in differentiating multiple small hemorrhages from multiple small calcifications in brain tumors by computed tomography (CT) is discussed. Illustrative CT scans are presented and the theoretical basis for this problem is elaborated. The difficulty is attributed to the relatively large size of the voxel and the ensuing partial volume effect, particularly with small intraparenchymal lesions of different sizes and attenuations."}
{"id": "PMID:214871", "title": "[New therapeutical possibility in a geriatric practice (author's transl)].", "content": "Thirty four patients whose ages ranged for 60 to 101 were treated with \"tiapride\" in a geriatric hospital. The patients' tolerance of the drug was excellent even the very elderly whose circulatory or respiratory state was often rather poor. The results obtained were good for the cases of acute or chronic agitation. They were satisfactory as regards a certain number of abnormal movements and some painful syndromes. However the number of these cases was too small for the results to be considered significant.", "contents": "[New therapeutical possibility in a geriatric practice (author's transl)]. Thirty four patients whose ages ranged for 60 to 101 were treated with \"tiapride\" in a geriatric hospital. The patients' tolerance of the drug was excellent even the very elderly whose circulatory or respiratory state was often rather poor. The results obtained were good for the cases of acute or chronic agitation. They were satisfactory as regards a certain number of abnormal movements and some painful syndromes. However the number of these cases was too small for the results to be considered significant."}
{"id": "PMID:214892", "title": "Multicentric tracheobronchial and oesophageal granular cell myoblastoma.", "content": "Two patients with multiple intrathorcic granular cell myoblastomas are described. In one case multiple tumours were present in the major airways and oesophagus. The patient presented with recurrent pulmonary infections and stridor due to airway obstruction. In the other case dysphagia caused by multiple oesophageal granular cell myoblastomas was the major symptom. Granular cell myoblastoma is a rare tumour of neurogenic origin with a characteristic histological appearance. The pattern of multiple tracheobranchial and oesophageal tumours is uncommon and forms the basis of this report.", "contents": "Multicentric tracheobronchial and oesophageal granular cell myoblastoma. Two patients with multiple intrathorcic granular cell myoblastomas are described. In one case multiple tumours were present in the major airways and oesophagus. The patient presented with recurrent pulmonary infections and stridor due to airway obstruction. In the other case dysphagia caused by multiple oesophageal granular cell myoblastomas was the major symptom. Granular cell myoblastoma is a rare tumour of neurogenic origin with a characteristic histological appearance. The pattern of multiple tracheobranchial and oesophageal tumours is uncommon and forms the basis of this report."}
{"id": "PMID:214895", "title": "A study of cyclic nucleotide metabolism and the histology of rat liver during 3'-methyl-4-dimethylamino-azobenzene carcinogenesis. II. Cyclic AMP metabolism.", "content": "We have studied cAMP metabolism in rat livers undergoing carcinogenesis induced by dietary 3'-methyl-4-dimethylaminoazobenzene. A correlation between the biochemical and the histological changes described in the companion paper has been made. In this study, we saw 100% incidence of cholangiocarcinoma by 10 weeks. During weeks 1--10, the biochemistry of tumor-free areas of the livers only was studied; during weeks 11-13, the increased size of the tumors made possible a biochemical study of the tumor tissue as well as the non-tumor tissue, and a comparison between the two was made. Alterations in all parameters of cAMP metabolism were seen from the earliest stages of treatemnt. Most striking were those of adenylate cyclase activity which preceded and accompanied tumor formation, and were seen in both non-tumor and tumor tissue. In the first few weeks of treatment, small acidophilic glycogen-deficient hepatocytes appeared in the periportal areas of the liver lobules. During this time, there was an increase in maximal isoproterenol stimulation of adenylate cyclase and to a lesser extent in the basal activity of the enzyme; increases in phosphodiesterase activity were seen, and were greatest in weeks 1, 2; cAMP levels were diminished in weeks 1, 2 and slightly but not significantly elevated at week 3. From week 4 onwards an even smaller glycogen-deficient cell population appeared in perilobular areas amongst the acidophilic hepatocytes, and tumors began to appear elsewhere in the livers; at this time, there were further marked increases in the basal activity and isoproterenol responsiveness of adenylate cyclase, and the appearance of increased Gpp(NH)p responsiveness of the enzyme; the increase in phosphodiesterase activities seen at week 3 (smaller than that seen in weeks 1, 2) was sustained but did not further increase; cAMP levels were now significantly elevated also, but they did not rise steadily as did the activity of adenylate cyclase. There was a marked difference between the adenylate cyclase activities in non-tumor tissue from tumor-bearing and non-tumor-bearing livers in weeks 4--10, but there was no difference between the phosphodiesterase activities or cAMP levels in these two groups. Adenylate cyclase activity was extremely high in both non-tumor tissue of tumor-bearing livers from weeks 4--10 and tumors from weeks 11--13. Although phosphodiesterase activities were most elevated in the tumors, there were extremely high cyclic AMP levels in these tissues. The difference between the cAMP levels of tumor and non-tumor tissue was striking. Our findings are discussed with respect to the two-state model of carcinogenesis...", "contents": "A study of cyclic nucleotide metabolism and the histology of rat liver during 3'-methyl-4-dimethylamino-azobenzene carcinogenesis. II. Cyclic AMP metabolism. We have studied cAMP metabolism in rat livers undergoing carcinogenesis induced by dietary 3'-methyl-4-dimethylaminoazobenzene. A correlation between the biochemical and the histological changes described in the companion paper has been made. In this study, we saw 100% incidence of cholangiocarcinoma by 10 weeks. During weeks 1--10, the biochemistry of tumor-free areas of the livers only was studied; during weeks 11-13, the increased size of the tumors made possible a biochemical study of the tumor tissue as well as the non-tumor tissue, and a comparison between the two was made. Alterations in all parameters of cAMP metabolism were seen from the earliest stages of treatemnt. Most striking were those of adenylate cyclase activity which preceded and accompanied tumor formation, and were seen in both non-tumor and tumor tissue. In the first few weeks of treatment, small acidophilic glycogen-deficient hepatocytes appeared in the periportal areas of the liver lobules. During this time, there was an increase in maximal isoproterenol stimulation of adenylate cyclase and to a lesser extent in the basal activity of the enzyme; increases in phosphodiesterase activity were seen, and were greatest in weeks 1, 2; cAMP levels were diminished in weeks 1, 2 and slightly but not significantly elevated at week 3. From week 4 onwards an even smaller glycogen-deficient cell population appeared in perilobular areas amongst the acidophilic hepatocytes, and tumors began to appear elsewhere in the livers; at this time, there were further marked increases in the basal activity and isoproterenol responsiveness of adenylate cyclase, and the appearance of increased Gpp(NH)p responsiveness of the enzyme; the increase in phosphodiesterase activities seen at week 3 (smaller than that seen in weeks 1, 2) was sustained but did not further increase; cAMP levels were now significantly elevated also, but they did not rise steadily as did the activity of adenylate cyclase. There was a marked difference between the adenylate cyclase activities in non-tumor tissue from tumor-bearing and non-tumor-bearing livers in weeks 4--10, but there was no difference between the phosphodiesterase activities or cAMP levels in these two groups. Adenylate cyclase activity was extremely high in both non-tumor tissue of tumor-bearing livers from weeks 4--10 and tumors from weeks 11--13. Although phosphodiesterase activities were most elevated in the tumors, there were extremely high cyclic AMP levels in these tissues. The difference between the cAMP levels of tumor and non-tumor tissue was striking. Our findings are discussed with respect to the two-state model of carcinogenesis..."}
{"id": "PMID:214896", "title": "Hormonal activation of mammary gland peroxidase.", "content": "Ultrastructural cytochemistry was used to detect an endogenous peroxidase in the rat mammary gland. The enzyme was identified only during the latter half of pregnancy and during lactation, indicating its possible dependence upon hormones. To test this hypothesis, specific hormones associated with the development and differentiation of the mammary gland were used both in vivo and in vitro in an effort to induce, or unmask, the activity of the enzyme. Estrogen injected into nonpregnant rats induced some peroxidase activity in the mammary glands of a few animals. Two hormone combinations tested in organ cultures of mouse mammary gland were able to activate the enzyme: (1) dexamethasone + insulin and (2) dexamethasone + insulin + prolactin.", "contents": "Hormonal activation of mammary gland peroxidase. Ultrastructural cytochemistry was used to detect an endogenous peroxidase in the rat mammary gland. The enzyme was identified only during the latter half of pregnancy and during lactation, indicating its possible dependence upon hormones. To test this hypothesis, specific hormones associated with the development and differentiation of the mammary gland were used both in vivo and in vitro in an effort to induce, or unmask, the activity of the enzyme. Estrogen injected into nonpregnant rats induced some peroxidase activity in the mammary glands of a few animals. Two hormone combinations tested in organ cultures of mouse mammary gland were able to activate the enzyme: (1) dexamethasone + insulin and (2) dexamethasone + insulin + prolactin."}
{"id": "PMID:214904", "title": "A new approach to the difficult assessment of aldosterone secretion in anephric patients.", "content": "A new method for the assessment of endogenous formation of aldosterone in anephric patients is described. (1, 2-3H) aldosterone was administered i.v. to patients 1-2 days before hemodialysis, and then the specific activity (SA) of tetrahydroaldosterone glucosiduronate, the major aldosterone metabolite, was measured in the dialysate using a specific radioimmunoassay. The aldosterone secretion rate was determined from the extent of isotope dilution by endogenous metabolite. Aldosterone secretion rates measured in 10 patients were for the most part low. The secretion rate determined in blood from the aldosterone metabolic clearance rate and plasma aldosterone concentration closely approximate secretion rate values obtained by the isotope dilution method in 3 of 4 patients. In 2 patients in whom ACTH was administered chronically, radio-labeled aldosterone was administered at the start of the study and then the day to day aldosterone secretory response to ACTH was determined from the SA of tetrahydroaldosterone in blood. Aldosterone secretion continuously increased for as long as ACTH was administered.", "contents": "A new approach to the difficult assessment of aldosterone secretion in anephric patients. A new method for the assessment of endogenous formation of aldosterone in anephric patients is described. (1, 2-3H) aldosterone was administered i.v. to patients 1-2 days before hemodialysis, and then the specific activity (SA) of tetrahydroaldosterone glucosiduronate, the major aldosterone metabolite, was measured in the dialysate using a specific radioimmunoassay. The aldosterone secretion rate was determined from the extent of isotope dilution by endogenous metabolite. Aldosterone secretion rates measured in 10 patients were for the most part low. The secretion rate determined in blood from the aldosterone metabolic clearance rate and plasma aldosterone concentration closely approximate secretion rate values obtained by the isotope dilution method in 3 of 4 patients. In 2 patients in whom ACTH was administered chronically, radio-labeled aldosterone was administered at the start of the study and then the day to day aldosterone secretory response to ACTH was determined from the SA of tetrahydroaldosterone in blood. Aldosterone secretion continuously increased for as long as ACTH was administered."}
{"id": "PMID:214906", "title": "The differentiation of invasive and non-invasive Entamoeba histolytica by isoenzyme electrophoresis.", "content": "Cultures of 85 stocks of Entamoeba histolytica were compared by electrophoretic patterns of three enzymes: glucosephosphate isomerase, phosphoglucomutase and L-malate: NADP+ oxidoreductase (oxaloacetate-decarboxylating). Four groups of E. histolytica stocks have been distinguished. 18 of these stocks were derived from individual patients with clinical amoebiasis and all of these were of one enzyme group, which did not occur among the other stocks.", "contents": "The differentiation of invasive and non-invasive Entamoeba histolytica by isoenzyme electrophoresis. Cultures of 85 stocks of Entamoeba histolytica were compared by electrophoretic patterns of three enzymes: glucosephosphate isomerase, phosphoglucomutase and L-malate: NADP+ oxidoreductase (oxaloacetate-decarboxylating). Four groups of E. histolytica stocks have been distinguished. 18 of these stocks were derived from individual patients with clinical amoebiasis and all of these were of one enzyme group, which did not occur among the other stocks."}
{"id": "PMID:214907", "title": "Leishmania donovani: ultrastructural localization of diaminobenzidine reactivity in the amastigotes.", "content": "Intracellular amastigotes of Leishmania donovani obtained from spleens of infected hamsters were studied by means of the diaminobenzidine technique for the presence of cytochromes and the activities of cytochrome oxidase and peroxidase. In the absence of H2O2, the oxidation of DAB, evidenced by electron-dense deposits localized on the cristae, inclusions, and enveloping membranes of the mitochondria and kinetoplast, revealed the activity of the cytochrome oxidase and the presence of the cytochromes. The increased deposition of DAB oxidation especially on the enveloping membranes in the presence of H2O2 suggests the activity of a peroxidase, probably cytochrome c peroxidase.", "contents": "Leishmania donovani: ultrastructural localization of diaminobenzidine reactivity in the amastigotes. Intracellular amastigotes of Leishmania donovani obtained from spleens of infected hamsters were studied by means of the diaminobenzidine technique for the presence of cytochromes and the activities of cytochrome oxidase and peroxidase. In the absence of H2O2, the oxidation of DAB, evidenced by electron-dense deposits localized on the cristae, inclusions, and enveloping membranes of the mitochondria and kinetoplast, revealed the activity of the cytochrome oxidase and the presence of the cytochromes. The increased deposition of DAB oxidation especially on the enveloping membranes in the presence of H2O2 suggests the activity of a peroxidase, probably cytochrome c peroxidase."}
{"id": "PMID:214910", "title": "[Effect of single exposure to the carcinogen 4-dimethylaminoazobenzene on several properties of rat liver mitochondria].", "content": "The hepatospecific carcinogen 4-dimethylaminoazobenzene (DAB), applied as a single interperitoneal injection, induced no changes in the activity of mitochondrial and cytoplasmic malate-dehydrogenase in the rat liver. The same carcinogen and non-carcinogenic isomer 4-diethylaminoazobenzene brought about decreased activity of cytochromeoxidase in isolated rat liver mitochondria. During 18 days after a single interperitoneal injection of DAB the swelling-contraction properties of isolated liver mitochondria were seen altered in the presence of succinate and ATP whereas DAB exerted no influence on mitochondria from the kidney, which organ is not a target-tissue for carcinogenic action.", "contents": "[Effect of single exposure to the carcinogen 4-dimethylaminoazobenzene on several properties of rat liver mitochondria]. The hepatospecific carcinogen 4-dimethylaminoazobenzene (DAB), applied as a single interperitoneal injection, induced no changes in the activity of mitochondrial and cytoplasmic malate-dehydrogenase in the rat liver. The same carcinogen and non-carcinogenic isomer 4-diethylaminoazobenzene brought about decreased activity of cytochromeoxidase in isolated rat liver mitochondria. During 18 days after a single interperitoneal injection of DAB the swelling-contraction properties of isolated liver mitochondria were seen altered in the presence of succinate and ATP whereas DAB exerted no influence on mitochondria from the kidney, which organ is not a target-tissue for carcinogenic action."}
{"id": "PMID:214912", "title": "[Morphology of the surface of normal and virus transformed cells in vitro].", "content": "The cell surface morphology of two cell lines--from the mink lung (Mv1Lu) and from the Kirsten sarcoma virus transformed derivate (Ki-Mv1Lu)--was studied by scanning electron microscopy. Marked differences are seen in cell morphology of these two lines at high cell densities. Mv1Lu cells at high densities had uniform flat polygonal shape with microvilli at their surface. A marked diversity in cell morphology was characteristic of Ki-Mv1Lu cells at comparable cell densities: variation in shape, in thickness degrees, and in the expression of cell surface ultrastructure (microvilli, blebs, filopodia). No dependence of Ki-Mv1Lu cell morphology from cell densities was observed. At low cell densities of Mv1Lu cells, cells with the morphology differing from the typical pattern of confluent Mv1Lu cells were seen. Morphological diversity of these cells was comparable with that of Ki-Mv1Lu cells. Nothing has been found in cell surface morphology that could be absolutely specific for transformed cells only.", "contents": "[Morphology of the surface of normal and virus transformed cells in vitro]. The cell surface morphology of two cell lines--from the mink lung (Mv1Lu) and from the Kirsten sarcoma virus transformed derivate (Ki-Mv1Lu)--was studied by scanning electron microscopy. Marked differences are seen in cell morphology of these two lines at high cell densities. Mv1Lu cells at high densities had uniform flat polygonal shape with microvilli at their surface. A marked diversity in cell morphology was characteristic of Ki-Mv1Lu cells at comparable cell densities: variation in shape, in thickness degrees, and in the expression of cell surface ultrastructure (microvilli, blebs, filopodia). No dependence of Ki-Mv1Lu cell morphology from cell densities was observed. At low cell densities of Mv1Lu cells, cells with the morphology differing from the typical pattern of confluent Mv1Lu cells were seen. Morphological diversity of these cells was comparable with that of Ki-Mv1Lu cells. Nothing has been found in cell surface morphology that could be absolutely specific for transformed cells only."}
{"id": "PMID:214913", "title": "[Electron microscopic study of glycocalyx formation in different functional states of the frog bladder epithelial cells].", "content": "The apical part of the urinary bladder granular cells contains oval granules filled with a homogenous substance; close to the plasma membrane granules with tubular element are disposed. A preliminary 30 min fixation of the bladder epithelium with 0.1--0.5% glutaraldehyde followed by 2.5% glutaraldehyde post-fixation rather increased the number of granules with the orderly distributed inner material. The membrane of these granules includes in to the plasma membrane. The loosening of the inner material takes place and the fibrillar elements similar in structure to the glycocalix fibrilles attach to the external surface of the cell plasma membrane.", "contents": "[Electron microscopic study of glycocalyx formation in different functional states of the frog bladder epithelial cells]. The apical part of the urinary bladder granular cells contains oval granules filled with a homogenous substance; close to the plasma membrane granules with tubular element are disposed. A preliminary 30 min fixation of the bladder epithelium with 0.1--0.5% glutaraldehyde followed by 2.5% glutaraldehyde post-fixation rather increased the number of granules with the orderly distributed inner material. The membrane of these granules includes in to the plasma membrane. The loosening of the inner material takes place and the fibrillar elements similar in structure to the glycocalix fibrilles attach to the external surface of the cell plasma membrane."}
{"id": "PMID:214914", "title": "[Effect of cAMP on the structural and functional properties of the erythrocytes].", "content": "Cyclic AMP inhibits the anion transport and decreases the osmotic resistance and deformability of erythrocytes with the normal level of ATP. With ATP-depleted erythrocytes cAMP exerted the opposite effects on the corresponding characteristics. In addition, it was observed that the pattern of cAMP effect on the cell form depends on the basal level of ATP. These effects may be associated with the two types of structural rearrangements of erythrocyte membranes established earlier: a cooperative transition not connected with protein kinase system, and a non-cooperative one caused by protein phosphorilation.", "contents": "[Effect of cAMP on the structural and functional properties of the erythrocytes]. Cyclic AMP inhibits the anion transport and decreases the osmotic resistance and deformability of erythrocytes with the normal level of ATP. With ATP-depleted erythrocytes cAMP exerted the opposite effects on the corresponding characteristics. In addition, it was observed that the pattern of cAMP effect on the cell form depends on the basal level of ATP. These effects may be associated with the two types of structural rearrangements of erythrocyte membranes established earlier: a cooperative transition not connected with protein kinase system, and a non-cooperative one caused by protein phosphorilation."}
{"id": "PMID:214915", "title": "[Correlation of Na,K-ATPase activity and protein synthesis in nerve cell membranes exposed to acetylcholine].", "content": "Acetylcholine (10(-6)--10(-3) M) added to the rat brain homogenate increased that activity of microsomal Na, K-ATPase and (14C)-amino acid incorporation in microsomal proteins. Actinomicin D (5.10(-5) M) eliminated the effect of acetylcholine. It is concluded that acetylcholine induced the synthesis of either Na, K-ATPase itself or some other proteins involved in the enzyme activity regulation.", "contents": "[Correlation of Na,K-ATPase activity and protein synthesis in nerve cell membranes exposed to acetylcholine]. Acetylcholine (10(-6)--10(-3) M) added to the rat brain homogenate increased that activity of microsomal Na, K-ATPase and (14C)-amino acid incorporation in microsomal proteins. Actinomicin D (5.10(-5) M) eliminated the effect of acetylcholine. It is concluded that acetylcholine induced the synthesis of either Na, K-ATPase itself or some other proteins involved in the enzyme activity regulation."}
{"id": "PMID:214916", "title": "[Effect of the critical fragmentation of erythrocyte membranes].", "content": "After sonification of erythrocyte membranes, some changes were registered in these including a loss of their ability to structural rearrangements caused by cAMP (ESR-spectroscopy and luminescence data), an increase in cAMP binding and aggregation of intramembrane particles (freeze-fracture data). These findings suggest a non-identity of the structural organization in membranes and in their fragments. The cooperative nature of membrane structural modification at ultrasonic fragmentation is shown.", "contents": "[Effect of the critical fragmentation of erythrocyte membranes]. After sonification of erythrocyte membranes, some changes were registered in these including a loss of their ability to structural rearrangements caused by cAMP (ESR-spectroscopy and luminescence data), an increase in cAMP binding and aggregation of intramembrane particles (freeze-fracture data). These findings suggest a non-identity of the structural organization in membranes and in their fragments. The cooperative nature of membrane structural modification at ultrasonic fragmentation is shown."}
{"id": "PMID:214917", "title": "[Formation of heterosymplasts in human reticular cell cultures].", "content": "The cell fusion has been studied in human reticular cell cultures J-96 and J-41 treated with the Sendai virus or with polyethylene glycol 1000 and 6000. The J-96 cells have a high alkaline phosphatase activity, in J-41 cells the enzyme is not detectable. No heterogenous alkaline phosphatase activity was seen in the protoplasm of symplasts 18 hours after virus cell fusion. It has been shown with polyethylene glycol treatment that during the fusion of cells J-96 and J-41 the enzyme activity was spreading over the symplast protoplasm.", "contents": "[Formation of heterosymplasts in human reticular cell cultures]. The cell fusion has been studied in human reticular cell cultures J-96 and J-41 treated with the Sendai virus or with polyethylene glycol 1000 and 6000. The J-96 cells have a high alkaline phosphatase activity, in J-41 cells the enzyme is not detectable. No heterogenous alkaline phosphatase activity was seen in the protoplasm of symplasts 18 hours after virus cell fusion. It has been shown with polyethylene glycol treatment that during the fusion of cells J-96 and J-41 the enzyme activity was spreading over the symplast protoplasm."}
{"id": "PMID:214918", "title": "[On corticosteroid control of NAD splitting in rat liver].", "content": "Hydrocortisone increases the NAD-glycohydrolase activity in the liver of intact rats. Actinomycin D does not influence the stimulating effect of hydrocartisone with respect to the NADase activity of the liver. The degree of activation of NAD enzymic splitting with administration of 200 mg/kg of nicotinamide depends on the initial hormonal background: with hypercorticoidism it is higher and with hypocorticoidism it is lower than the level found in the intact animals which were given the same dose of the vitamin. An inverse correlation between the steroid-dependent shifts of the NADase activity and the content of NAD in the liver may evidence for their interdependence. A conclusion is drawan on the paramount importance of corticosteroid control of the nucleotide splitting in vivo for formation of NAD cellular pool.", "contents": "[On corticosteroid control of NAD splitting in rat liver]. Hydrocortisone increases the NAD-glycohydrolase activity in the liver of intact rats. Actinomycin D does not influence the stimulating effect of hydrocartisone with respect to the NADase activity of the liver. The degree of activation of NAD enzymic splitting with administration of 200 mg/kg of nicotinamide depends on the initial hormonal background: with hypercorticoidism it is higher and with hypocorticoidism it is lower than the level found in the intact animals which were given the same dose of the vitamin. An inverse correlation between the steroid-dependent shifts of the NADase activity and the content of NAD in the liver may evidence for their interdependence. A conclusion is drawan on the paramount importance of corticosteroid control of the nucleotide splitting in vivo for formation of NAD cellular pool."}
{"id": "PMID:214923", "title": "Oral calcium tolerance and urinary cyclic AMP in urolithiasis.", "content": "Oral calcium tolerance and urinary cyclic AMP testing was used in the evaluation of 61 unselected patients with stones. The oral calcium tolerance test was easy to perform and was useful in defining several distinct metabolic abnormalities contributing to calculous formation. Oral calcium tolerance testing is more precise than twenty-four-hour urinary calcium determination and should provide a means of determining proper medical treatment of urolithiasis. Urinary cyclic AMP was disappointing as a measure of parathormone activity.", "contents": "Oral calcium tolerance and urinary cyclic AMP in urolithiasis. Oral calcium tolerance and urinary cyclic AMP testing was used in the evaluation of 61 unselected patients with stones. The oral calcium tolerance test was easy to perform and was useful in defining several distinct metabolic abnormalities contributing to calculous formation. Oral calcium tolerance testing is more precise than twenty-four-hour urinary calcium determination and should provide a means of determining proper medical treatment of urolithiasis. Urinary cyclic AMP was disappointing as a measure of parathormone activity."}
{"id": "PMID:214924", "title": "Recognition of virally transformed cells by lymphocytes from patients with prostatic cancer.", "content": "Data presented describe the first assay using human peripheral blood lymphocytes (PBL) against two unique virally transformed cell lines in vitro. Human cells transformed by a cytomegalovirus (CMV-Mj) isolated from normal human prostate tissue were used as target cells in microcytoxicity assays with lymphocytes from 100 patients. Three target cell types were used: control human embryonic lung cells (HEL), transformed HEL cells (CMV-Mj-HEL-2), and transformed HEL cells retrieved from tumors induced in athymic nude mice (CMV-Mj-HEL-2, T-1) by injection of CMV-Mj-HEL-2 cells. PBL preparations from 84% of all patients tested significantly killed CMV-Mj-HEL-2, T-1 cells. However, only PBL from patients with prostatic carcinoma were cytotoxic for CMV-Mj-HEL-2 cells significantly more often than for control HEL. The implications of this approach are discussed.", "contents": "Recognition of virally transformed cells by lymphocytes from patients with prostatic cancer. Data presented describe the first assay using human peripheral blood lymphocytes (PBL) against two unique virally transformed cell lines in vitro. Human cells transformed by a cytomegalovirus (CMV-Mj) isolated from normal human prostate tissue were used as target cells in microcytoxicity assays with lymphocytes from 100 patients. Three target cell types were used: control human embryonic lung cells (HEL), transformed HEL cells (CMV-Mj-HEL-2), and transformed HEL cells retrieved from tumors induced in athymic nude mice (CMV-Mj-HEL-2, T-1) by injection of CMV-Mj-HEL-2 cells. PBL preparations from 84% of all patients tested significantly killed CMV-Mj-HEL-2, T-1 cells. However, only PBL from patients with prostatic carcinoma were cytotoxic for CMV-Mj-HEL-2 cells significantly more often than for control HEL. The implications of this approach are discussed."}
{"id": "PMID:214925", "title": "Adult renal myoepithelial hamartoma.", "content": "A renal myoepithelial hamartoma presented as a lucent filling defect with gross hematuria in an adult female. Preoperative studies caused conflicting impressions. The predominance of smooth muscle and incorporated tubuloepithelial elements characterize the tumor as a hamartoma of myoepithelial type. Pertinent review of the literature confirms the rarity of this lesion in adults.", "contents": "Adult renal myoepithelial hamartoma. A renal myoepithelial hamartoma presented as a lucent filling defect with gross hematuria in an adult female. Preoperative studies caused conflicting impressions. The predominance of smooth muscle and incorporated tubuloepithelial elements characterize the tumor as a hamartoma of myoepithelial type. Pertinent review of the literature confirms the rarity of this lesion in adults."}
{"id": "PMID:214919", "title": "[Hyperlipemia and lipoprotein blood spectrum of rabbits of different age with administration of cholesterol].", "content": "Hyperlipemia developing in impuberal, young and old rabbits with administered cholesterol is characterized by a considerable prevailence of the cholesterol level over the triglyceride one. The degree of shifts in lipids depends on the age, it is most pronounced in old animals and the least pronounced in impuberal ones. The amount of blood serum cholesterol bound with lipoproteids of high density lowers and most considerably in old rabbits. Separation of blood serum lipoproteids by electrophoresis in polyacrylamide gel detects in rabbits with hyperlipemia a sharp decrease as compared to the norm in the intensity of alpha-lipoproteids disc. This decrease is most pronounced in animals of older age groups. The presence of the intermediate fraction between pre-beta- and beta-lipoproteids is also found in the same animal by the separation especially often in old animals.", "contents": "[Hyperlipemia and lipoprotein blood spectrum of rabbits of different age with administration of cholesterol]. Hyperlipemia developing in impuberal, young and old rabbits with administered cholesterol is characterized by a considerable prevailence of the cholesterol level over the triglyceride one. The degree of shifts in lipids depends on the age, it is most pronounced in old animals and the least pronounced in impuberal ones. The amount of blood serum cholesterol bound with lipoproteids of high density lowers and most considerably in old rabbits. Separation of blood serum lipoproteids by electrophoresis in polyacrylamide gel detects in rabbits with hyperlipemia a sharp decrease as compared to the norm in the intensity of alpha-lipoproteids disc. This decrease is most pronounced in animals of older age groups. The presence of the intermediate fraction between pre-beta- and beta-lipoproteids is also found in the same animal by the separation especially often in old animals."}
{"id": "PMID:214922", "title": "[Characteristics of surface-active substances effect on K+-dependent phosphatase activity of brain tissue].", "content": "The K+-acetylphosphatase and K+-p-nitrophenylphosphatase activities in the fraction of brain microsomes were studied as affected by anionic (sodium desoxycholate and sodium dodecyl sulphate) and nonionic (triton X-100 and digitonin) surface-active substances. The most activating concentrations of these substances are determined and their similarity with those for Na+, K+-ATPase is marked. According to the character of the effect on the K+-phosphatase and Na+, K+-ATPase activities, the studied surface-active substances are grouped on the basis of the molecule configurations, rather than ionogenic factor. Their activating effect is supposed to result from an increase in the number of functioning catalytic centres rather than the molecular activity of the enzyme. It is shown that the digitonin high concentrations may completely inhibit the Na+, K+-ATPase activity and to some extent retain the K+-acetylphosphatase activity.", "contents": "[Characteristics of surface-active substances effect on K+-dependent phosphatase activity of brain tissue]. The K+-acetylphosphatase and K+-p-nitrophenylphosphatase activities in the fraction of brain microsomes were studied as affected by anionic (sodium desoxycholate and sodium dodecyl sulphate) and nonionic (triton X-100 and digitonin) surface-active substances. The most activating concentrations of these substances are determined and their similarity with those for Na+, K+-ATPase is marked. According to the character of the effect on the K+-phosphatase and Na+, K+-ATPase activities, the studied surface-active substances are grouped on the basis of the molecule configurations, rather than ionogenic factor. Their activating effect is supposed to result from an increase in the number of functioning catalytic centres rather than the molecular activity of the enzyme. It is shown that the digitonin high concentrations may completely inhibit the Na+, K+-ATPase activity and to some extent retain the K+-acetylphosphatase activity."}
{"id": "PMID:214920", "title": "[Contents of catecholamines and corticosteroids in tissues of quinea pigs with C-hypovitaminosis].", "content": "On the 12-14th day of the scorbutigenic regime simultaneously with a decrease in the level of ascorbic acid in the guinea pig tissues to content of catecholamines and 11-oxycorticosteroids changes as well. The amount of adrenalin in the adrenal tissue drops, that of epinephrine in the brain tissue and liver rises. The content of glucocorticoids in adrenals and blood plasm increases. Against a background of vitamin C deficiency administration of ACTH does not cause any deviations in the level of catecholamines in tissues, of 11-oxycorticosteroids in the adrenals tissue and increase insignificantly the content of the latter in blood plasm.", "contents": "[Contents of catecholamines and corticosteroids in tissues of quinea pigs with C-hypovitaminosis]. On the 12-14th day of the scorbutigenic regime simultaneously with a decrease in the level of ascorbic acid in the guinea pig tissues to content of catecholamines and 11-oxycorticosteroids changes as well. The amount of adrenalin in the adrenal tissue drops, that of epinephrine in the brain tissue and liver rises. The content of glucocorticoids in adrenals and blood plasm increases. Against a background of vitamin C deficiency administration of ACTH does not cause any deviations in the level of catecholamines in tissues, of 11-oxycorticosteroids in the adrenals tissue and increase insignificantly the content of the latter in blood plasm."}
{"id": "PMID:214921", "title": "[Effect of potassium orotate on metabolism in chickens under different provision with vitamin D3].", "content": "Vitamin D3 induction of the vitamin-D3-dependent proteins biosynthesis and certain indexes characterizing the rachitic state in animals were studied as affected by potassium orotate. Introduction of potassium orotate to the rachitogenic diet in combination with vitamin D3 is shown to normalize the processess of bone mineralization and to increase intensity of chicken growth. In duodenum mucosa with rachitis orotate normalizes the activity of alkaline phosphatase, raises the content of calcium-binding protein and stimulates the latter formation after administration of vitamin D3; orotate favours redistribution of the purine and pyrimidine nucleotides content. Radioactive orotic acid is subjected to intensive metabolism in mucosa and is converted to nucleotides of pool and RNA.", "contents": "[Effect of potassium orotate on metabolism in chickens under different provision with vitamin D3]. Vitamin D3 induction of the vitamin-D3-dependent proteins biosynthesis and certain indexes characterizing the rachitic state in animals were studied as affected by potassium orotate. Introduction of potassium orotate to the rachitogenic diet in combination with vitamin D3 is shown to normalize the processess of bone mineralization and to increase intensity of chicken growth. In duodenum mucosa with rachitis orotate normalizes the activity of alkaline phosphatase, raises the content of calcium-binding protein and stimulates the latter formation after administration of vitamin D3; orotate favours redistribution of the purine and pyrimidine nucleotides content. Radioactive orotic acid is subjected to intensive metabolism in mucosa and is converted to nucleotides of pool and RNA."}
{"id": "PMID:214934", "title": "[Effect of several drugs and nonspecific substances on the uterine microflora of cows during the puerperal period and at the time of impregnation].", "content": "A total of fifty Bulgarian Brown cows were used to test the effect of some hormonal and therapeutic preparations in combination with unspecific agents, having an irritation effect on the reticuloendothelial system, to establish their action on the quantitative and qualitative changes in the microbial flora of the uterus and the impregnantion of cows after calving. It was found that treatment after normal calving with 200,000 IU vitestrol and 20 IV hypophysin, and after rejection of the placenta with 2 g chloramphenicol, 15 g ac. citricum or sodium citrate and 0.2 g pilocarpinum hydrochloricum, coupled with the injection of 30-40 cm3 Filatov's tissue emulsion 8n the 5th day lowered the microbial count in the uterus by to 30.12% from the 1st to the 5th day and by 6.46 to 12.78% from the 10th to the 20th day. Parallel drop was established in the number of microbial species by 42%. Besides, it was noted that the cases of retentio secundinarum among the test cows and the number of cows with acute endometritis after calving decreased by 12%, on an average, the service period became shorter by 12.04 days, and the rate of conception at first insemination rose by 12% as compared with the controls.", "contents": "[Effect of several drugs and nonspecific substances on the uterine microflora of cows during the puerperal period and at the time of impregnation]. A total of fifty Bulgarian Brown cows were used to test the effect of some hormonal and therapeutic preparations in combination with unspecific agents, having an irritation effect on the reticuloendothelial system, to establish their action on the quantitative and qualitative changes in the microbial flora of the uterus and the impregnantion of cows after calving. It was found that treatment after normal calving with 200,000 IU vitestrol and 20 IV hypophysin, and after rejection of the placenta with 2 g chloramphenicol, 15 g ac. citricum or sodium citrate and 0.2 g pilocarpinum hydrochloricum, coupled with the injection of 30-40 cm3 Filatov's tissue emulsion 8n the 5th day lowered the microbial count in the uterus by to 30.12% from the 1st to the 5th day and by 6.46 to 12.78% from the 10th to the 20th day. Parallel drop was established in the number of microbial species by 42%. Besides, it was noted that the cases of retentio secundinarum among the test cows and the number of cows with acute endometritis after calving decreased by 12%, on an average, the service period became shorter by 12.04 days, and the rate of conception at first insemination rose by 12% as compared with the controls."}
{"id": "PMID:214935", "title": "[Clinico-epizootologic studies in Gumboro disease].", "content": "The disease was established on a poultry dressing combine, affecting birds at the age of three to eleven weeks. It ran its course with clinical symptoms and epizootiology that were characteristic of it. A total of 8778 birds or 10% succumbed to the disease. Its notification on a newly built poultry dressing combine made it reasonable to believe that possibility existed of its transmission through the hatcheries. The outbreak occurred almost simultaneously with the inadequate feeding that was admitted on the combine. The cyclogramme concerning the admission of birds and its strict application were shown to influence the course of the epizootic process. Clinical and epizootiological investigations coupled with virological and histopathological studies rendered it possible to draw the conclusion that the birds on the combine were affected with infectious bursitis, identified as Gumboro disease. It was established for the first time in this country.", "contents": "[Clinico-epizootologic studies in Gumboro disease]. The disease was established on a poultry dressing combine, affecting birds at the age of three to eleven weeks. It ran its course with clinical symptoms and epizootiology that were characteristic of it. A total of 8778 birds or 10% succumbed to the disease. Its notification on a newly built poultry dressing combine made it reasonable to believe that possibility existed of its transmission through the hatcheries. The outbreak occurred almost simultaneously with the inadequate feeding that was admitted on the combine. The cyclogramme concerning the admission of birds and its strict application were shown to influence the course of the epizootic process. Clinical and epizootiological investigations coupled with virological and histopathological studies rendered it possible to draw the conclusion that the birds on the combine were affected with infectious bursitis, identified as Gumboro disease. It was established for the first time in this country."}
{"id": "PMID:214936", "title": "[Immune response of pigs to Aujeszky disease virus and swine influenza virus].", "content": "Explored was the possibility of simultaneous vaccination of pigs against the Aujeszky's disease virus and the swine influenza virus. Used were strain MK-25 against the former and strain 3sb against the latter. It was found that at the simultaneous subcutaneous or oral treatment with the two antigens equally effective immunity was built as in the case of vaccination with each one of them used alone. No antagonism was established between the two antigens during the time of immunity building in the body.", "contents": "[Immune response of pigs to Aujeszky disease virus and swine influenza virus]. Explored was the possibility of simultaneous vaccination of pigs against the Aujeszky's disease virus and the swine influenza virus. Used were strain MK-25 against the former and strain 3sb against the latter. It was found that at the simultaneous subcutaneous or oral treatment with the two antigens equally effective immunity was built as in the case of vaccination with each one of them used alone. No antagonism was established between the two antigens during the time of immunity building in the body."}
{"id": "PMID:214937", "title": "Chronic lathyrism and atheromatosis in the rat. Study of the V.L.D.L. and plasma and arterial wall lipids.", "content": "Temporary chronic administration of Beta-amino-propionitrile (B.A.P.N.) produced morphological and biochemical changes of the aortic wall of rat as well as abnormalities of the plasma lipid levels. A hyperlipidic diet resulted in the blood plasma lipid abnormalities as B.A.P.N. intoxication. Nine weeks of B.A.P.N. followed by 42 weeks of a hyperlipidic diet increased the aortic cholesterol level and induced an atheroma. The diet alone produced only an endothelial lipid overload. The structure of arterial wall played the decisive role in atherogenesis.", "contents": "Chronic lathyrism and atheromatosis in the rat. Study of the V.L.D.L. and plasma and arterial wall lipids. Temporary chronic administration of Beta-amino-propionitrile (B.A.P.N.) produced morphological and biochemical changes of the aortic wall of rat as well as abnormalities of the plasma lipid levels. A hyperlipidic diet resulted in the blood plasma lipid abnormalities as B.A.P.N. intoxication. Nine weeks of B.A.P.N. followed by 42 weeks of a hyperlipidic diet increased the aortic cholesterol level and induced an atheroma. The diet alone produced only an endothelial lipid overload. The structure of arterial wall played the decisive role in atherogenesis."}
{"id": "PMID:214938", "title": "Malignant fibrous histiocytoma of the renal capsule. Light and electron microscopic study of a rare tumor.", "content": "This light microscopically pleomorphic tumor, which occurred in the renal capsule of 35-year-old female was diagnosed as a malignant fibrous histiocytoma. Ultrastructurally, the tumor showed two major components; fibroblast-like and histiocyte-like cells. This report stresses the rarity of such neoplasm in the kidney and also the usefulness of electron microscopy in establishing the diagnosis.", "contents": "Malignant fibrous histiocytoma of the renal capsule. Light and electron microscopic study of a rare tumor. This light microscopically pleomorphic tumor, which occurred in the renal capsule of 35-year-old female was diagnosed as a malignant fibrous histiocytoma. Ultrastructurally, the tumor showed two major components; fibroblast-like and histiocyte-like cells. This report stresses the rarity of such neoplasm in the kidney and also the usefulness of electron microscopy in establishing the diagnosis."}
{"id": "PMID:214939", "title": "Primary oat-cell carcinoma of the larynx.", "content": "A primary oat-cell carcinoma of the larynx in a 63-year-old man is reported. The oat-cell pattern appeared intermingled at one edge with a squamous carcinoma. The origin of this mixed tumour is considered together with the literature of extrapulmonary carcinomas having an oat-cell pattern.", "contents": "Primary oat-cell carcinoma of the larynx. A primary oat-cell carcinoma of the larynx in a 63-year-old man is reported. The oat-cell pattern appeared intermingled at one edge with a squamous carcinoma. The origin of this mixed tumour is considered together with the literature of extrapulmonary carcinomas having an oat-cell pattern."}
{"id": "PMID:214963", "title": "An epidemiological review of Japanese encephalitis.", "content": "Twenty-five years ago, Japanese encephalitis (JE) was known as an endemic, mosquito-borne disease in East Asia. Today, the causative virus is known to be distributed from maritime Siberia to the north, eastern India to the west, the Archipelago of Japan presumably the Philippines to the east, and from Indonesia to the south. Since the late-1960s, the geopathological status of JE epidemics has undergone considerable changes. The sizes of JE epidemics in Japan and China (Province of Taiwan) have steadily declined. In fact the JE virus itself appears to be disappearing from Japan. Long-term prediction of JE epidemics is more difficult for Korean Peninsula, nevertheless, reported JE morbidity rate in the Republic of Korea has remained at a relatively low level since 1969. In contrast to the trend in East Asia, new epidemic foci of JE have been emerging in the northern part of Tropical Eastern South Asia starting in 1969. Of particular importance are the continued high incidence (annual morbidity rate: 8.67-22.04/100 000) of reported JE in the northern part of Viet Nam between 1969 and 1974, and the high incidence (14.7/100 000) recorded in Chiang Mai Valley, Thailand, between 1969 and 1970. Apparently, the epidemic in Chiang Mai Valley spread to the neighbouring Shan State of Burma in 1974. Another JE epidemic broke out in West Bengal State, India in 1973. The occurrence of JE in the endemic zone south of these areas has remained sporadic. An increasing number of pathogens have been shown to cause signs and symptoms clinically indistinguishable from JE. In this review, the quality and international comparability of available JE statistics are also examined. Only a few countries and areas with reasonably developed statistical and laboratory services are able to provide national JE statistics in a form ready for epidemiological analysis. A practical surveillance system for JE needs to be organized in those countries where JE is a newly emerging health problem.", "contents": "An epidemiological review of Japanese encephalitis. Twenty-five years ago, Japanese encephalitis (JE) was known as an endemic, mosquito-borne disease in East Asia. Today, the causative virus is known to be distributed from maritime Siberia to the north, eastern India to the west, the Archipelago of Japan presumably the Philippines to the east, and from Indonesia to the south. Since the late-1960s, the geopathological status of JE epidemics has undergone considerable changes. The sizes of JE epidemics in Japan and China (Province of Taiwan) have steadily declined. In fact the JE virus itself appears to be disappearing from Japan. Long-term prediction of JE epidemics is more difficult for Korean Peninsula, nevertheless, reported JE morbidity rate in the Republic of Korea has remained at a relatively low level since 1969. In contrast to the trend in East Asia, new epidemic foci of JE have been emerging in the northern part of Tropical Eastern South Asia starting in 1969. Of particular importance are the continued high incidence (annual morbidity rate: 8.67-22.04/100 000) of reported JE in the northern part of Viet Nam between 1969 and 1974, and the high incidence (14.7/100 000) recorded in Chiang Mai Valley, Thailand, between 1969 and 1970. Apparently, the epidemic in Chiang Mai Valley spread to the neighbouring Shan State of Burma in 1974. Another JE epidemic broke out in West Bengal State, India in 1973. The occurrence of JE in the endemic zone south of these areas has remained sporadic. An increasing number of pathogens have been shown to cause signs and symptoms clinically indistinguishable from JE. In this review, the quality and international comparability of available JE statistics are also examined. Only a few countries and areas with reasonably developed statistical and laboratory services are able to provide national JE statistics in a form ready for epidemiological analysis. A practical surveillance system for JE needs to be organized in those countries where JE is a newly emerging health problem."}
{"id": "PMID:214966", "title": "Tumor cell interactions in vitro microtubules, 100 angstrom filaments, and contractile microfilaments of tumor cells involved in \"emperipolesis\".", "content": "An increase in the number of examples of emperiopolesis, i.e., cells within cells, was observed subsequently to addition of Bt2cAMP to spinner flask cultures of JB-1-E tumor cells. A conspicuous arrangement of microtubules and 100 angstrom filaments in the tumor cells involved in emperiopelesis was observed. Absence of emperipolesis in cultures treated with cytochalasin B indecates a possible role of the contractile microfilaments in the events leading to emperiopolesis. The significance of and the term emperipolesis are discussed.", "contents": "Tumor cell interactions in vitro microtubules, 100 angstrom filaments, and contractile microfilaments of tumor cells involved in \"emperipolesis\". An increase in the number of examples of emperiopolesis, i.e., cells within cells, was observed subsequently to addition of Bt2cAMP to spinner flask cultures of JB-1-E tumor cells. A conspicuous arrangement of microtubules and 100 angstrom filaments in the tumor cells involved in emperiopelesis was observed. Absence of emperipolesis in cultures treated with cytochalasin B indecates a possible role of the contractile microfilaments in the events leading to emperiopolesis. The significance of and the term emperipolesis are discussed."}
{"id": "PMID:214967", "title": "Nephroblastoma and neuroblastoma--histology and prognosis.", "content": "Statistically evaluating the influence of a histological grading, respectively of morphological differences on prognosis of nephroblastomas and neuroblastomas, better chances for survival become evident not only for earlier clinical stages, but also for nephroblastomas with high differentiation, or neuroblastomas with signs for differentiation. Only for neuroblastomas a relevant predeliction of tumors with signs of differentiation for the early clinical stage I is present. Combined subclassification according to clinical stages and histological grades results in 3 risk groups with different chances for survival. These 3 groups may play a role for specific therapeutic considerations.", "contents": "Nephroblastoma and neuroblastoma--histology and prognosis. Statistically evaluating the influence of a histological grading, respectively of morphological differences on prognosis of nephroblastomas and neuroblastomas, better chances for survival become evident not only for earlier clinical stages, but also for nephroblastomas with high differentiation, or neuroblastomas with signs for differentiation. Only for neuroblastomas a relevant predeliction of tumors with signs of differentiation for the early clinical stage I is present. Combined subclassification according to clinical stages and histological grades results in 3 risk groups with different chances for survival. These 3 groups may play a role for specific therapeutic considerations."}
{"id": "PMID:214968", "title": "Does lateral specialization apply to the frog's brain? An electron microscope observation.", "content": "The ultrastructure of polymorphic crystal-like inclusions occurring in the cytoplasm of neurons of only the medial portion of the left habenula has been studied in the adult frog Rana esculenta and in the tadpole with the use of three types of fixatives: osmium tetroxide, a mixture of aldehydes and potassium permanganate.", "contents": "Does lateral specialization apply to the frog's brain? An electron microscope observation. The ultrastructure of polymorphic crystal-like inclusions occurring in the cytoplasm of neurons of only the medial portion of the left habenula has been studied in the adult frog Rana esculenta and in the tadpole with the use of three types of fixatives: osmium tetroxide, a mixture of aldehydes and potassium permanganate."}
{"id": "PMID:214974", "title": "[Benign multilocular cystic nephroma (author's transl)].", "content": "A case of benign multilocular cystic nephroma in a 12 month old male infant is reported. The patho-anatomical features of this rare renal lesion are demonstrated. Its possible histogenesis and relationship to nephroblastoma are discussed.", "contents": "[Benign multilocular cystic nephroma (author's transl)]. A case of benign multilocular cystic nephroma in a 12 month old male infant is reported. The patho-anatomical features of this rare renal lesion are demonstrated. Its possible histogenesis and relationship to nephroblastoma are discussed."}
{"id": "PMID:214976", "title": "[Neurologic changes in systemic lupus erythematosus].", "content": "All the 200 observed cases of lupus erythematosus showed neurological changes. Among these patients in 17 cases lesions of the nervous system were the main manifestations. Certain neurological syndromes correlated with the degree of activity of the lupoid process. Prognostically unfavorable were developing strokes, convulsive syndromes, symptomatical psychoses, cerebral hypertensive syndrome, lesions of the spinal cord.", "contents": "[Neurologic changes in systemic lupus erythematosus]. All the 200 observed cases of lupus erythematosus showed neurological changes. Among these patients in 17 cases lesions of the nervous system were the main manifestations. Certain neurological syndromes correlated with the degree of activity of the lupoid process. Prognostically unfavorable were developing strokes, convulsive syndromes, symptomatical psychoses, cerebral hypertensive syndrome, lesions of the spinal cord."}
{"id": "PMID:214978", "title": "[Effect of cytotoxic hypoxia on the metabolism and ultrastructure of cortical synaptosomes and mitochondria].", "content": "The study is concerned with morphochemical changes in the metabolism and ultrastructure of the mitochondria and synaptical endings from the cortex of the hemispheres in rats under the influence of cyanide (7mg/kg) following 30 min, 2 hours and 24 hours after its administration. Subfractions of the light and heavy synaptosomes, as well as in the mitochondria of the cell bodies showed changes in the activity of the enzyme systems (cytochromoxidase, K+, Na+-ATPase and Mg2+-ATPase) and disturbances of the ultrastructure of the eliminated organella. After 24 hours the metabolism normalized, which may be explained by a biochemical brain plasticity at the subcellular level under conditions of histotoxic hypoxia.", "contents": "[Effect of cytotoxic hypoxia on the metabolism and ultrastructure of cortical synaptosomes and mitochondria]. The study is concerned with morphochemical changes in the metabolism and ultrastructure of the mitochondria and synaptical endings from the cortex of the hemispheres in rats under the influence of cyanide (7mg/kg) following 30 min, 2 hours and 24 hours after its administration. Subfractions of the light and heavy synaptosomes, as well as in the mitochondria of the cell bodies showed changes in the activity of the enzyme systems (cytochromoxidase, K+, Na+-ATPase and Mg2+-ATPase) and disturbances of the ultrastructure of the eliminated organella. After 24 hours the metabolism normalized, which may be explained by a biochemical brain plasticity at the subcellular level under conditions of histotoxic hypoxia."}
{"id": "PMID:214979", "title": "[Neuropsychological analysis of personality disorders in lesions of the frontal lobes of the brain].", "content": "The paper concerns some problems of disturbances in the most complicated forms of human behaviour and psyche in local brain lesions. A neuropsychological analysis of personality disturbances determines them as an integrative formation--a product of the work of the whole brain in social human activity. It is directed towards the distinguishing of \"components\" inside this formation and a study of the brain areas providing their functioning. In 63 patients with lesions of the left and right frontal lobes, as well as of deep areas of the right hemisphere, the authors studied the traits of self-evaluation (its 2 levels - cognitive: the knowledge of oneself, and emotional: feeling oneself) and emotional sphere. The data obtained indicate specific personality disorders with different localizations of brain lesions and, in particular, in lesions of the frontal lobe. Besides consolidated results given in the table, 2 cases (with pathology of the left and right frontal lobe) show principle differences in disorders of the emotional-personality sphere, related most likely to the localization of the pathological focus.", "contents": "[Neuropsychological analysis of personality disorders in lesions of the frontal lobes of the brain]. The paper concerns some problems of disturbances in the most complicated forms of human behaviour and psyche in local brain lesions. A neuropsychological analysis of personality disturbances determines them as an integrative formation--a product of the work of the whole brain in social human activity. It is directed towards the distinguishing of \"components\" inside this formation and a study of the brain areas providing their functioning. In 63 patients with lesions of the left and right frontal lobes, as well as of deep areas of the right hemisphere, the authors studied the traits of self-evaluation (its 2 levels - cognitive: the knowledge of oneself, and emotional: feeling oneself) and emotional sphere. The data obtained indicate specific personality disorders with different localizations of brain lesions and, in particular, in lesions of the frontal lobe. Besides consolidated results given in the table, 2 cases (with pathology of the left and right frontal lobe) show principle differences in disorders of the emotional-personality sphere, related most likely to the localization of the pathological focus."}
{"id": "PMID:214980", "title": "Interaction of metal ions with nucleic acids. Interaction of copper(II) with guanosine and its derivatives.", "content": "Interaction of copper(II) with guanosine, 2'-deoxyguanosine, 1-methylguanosine, 7-methylguanosine and GMP was studied withe use of spectroscopic and magneto-chemical methods. The main site of copper(II) binding in guanosine is nitrogen N-7; participation of N-1 is not excluded. The involvement of carbonyl oxygen in copper binding or copper chelation to N-7 and 0-6 is rather unlikely. A crystalline complex of copper(II) with GMP [Cu(C10H12O8N5P) .(H2O)3] was obtained, and it was demonstrated that copper(II) is bound with N-7 and the phosphate group.", "contents": "Interaction of metal ions with nucleic acids. Interaction of copper(II) with guanosine and its derivatives. Interaction of copper(II) with guanosine, 2'-deoxyguanosine, 1-methylguanosine, 7-methylguanosine and GMP was studied withe use of spectroscopic and magneto-chemical methods. The main site of copper(II) binding in guanosine is nitrogen N-7; participation of N-1 is not excluded. The involvement of carbonyl oxygen in copper binding or copper chelation to N-7 and 0-6 is rather unlikely. A crystalline complex of copper(II) with GMP [Cu(C10H12O8N5P) .(H2O)3] was obtained, and it was demonstrated that copper(II) is bound with N-7 and the phosphate group."}
{"id": "PMID:214982", "title": "The cyto-histopathology of a pseudomesotheliomatous carcinoma of the lung.", "content": "A cyto-histopathologic study of a pseudomesotheliomatous carcinoma of the lung has been presented. The cytologic preparations of the early morning and post-bronchoscopy sputum specimens, bronchial washings and pleural fluid contained tumor cells similar to those exfoliated from a terminal bronchiolar carcinoma, of which this neoplasm is considered a variant.", "contents": "The cyto-histopathology of a pseudomesotheliomatous carcinoma of the lung. A cyto-histopathologic study of a pseudomesotheliomatous carcinoma of the lung has been presented. The cytologic preparations of the early morning and post-bronchoscopy sputum specimens, bronchial washings and pleural fluid contained tumor cells similar to those exfoliated from a terminal bronchiolar carcinoma, of which this neoplasm is considered a variant."}
{"id": "PMID:214981", "title": "Selection of material for training cytotechnologists.", "content": "Out of 450 specially selected cases (gynecological and non-gynecological material) presented to 30 students during their educational program lasting 12 months, 20 cases caused the most problems. These 20 cases, in effect \"selected by the students\", were again presented as \"unknowns\" at the end of the course. The mean percentage of error improved from 64 per cent to 26 per cent. Furthermore, we gave the ten gynecological \"unknowns\" to ten cytotechnologists with at least five years' experience and their diagnoses were compared with those of the students at the end of the course. The majority of the diagnoses were similar with the exception of two cases: in one case the experienced cytotechnologists overlooked the scarce adenocarcinoma cells more often. In the other case follicular cervicitis was correctly diagnosed by the trained cytotechnologists but frequently misinterpreted by the students.", "contents": "Selection of material for training cytotechnologists. Out of 450 specially selected cases (gynecological and non-gynecological material) presented to 30 students during their educational program lasting 12 months, 20 cases caused the most problems. These 20 cases, in effect \"selected by the students\", were again presented as \"unknowns\" at the end of the course. The mean percentage of error improved from 64 per cent to 26 per cent. Furthermore, we gave the ten gynecological \"unknowns\" to ten cytotechnologists with at least five years' experience and their diagnoses were compared with those of the students at the end of the course. The majority of the diagnoses were similar with the exception of two cases: in one case the experienced cytotechnologists overlooked the scarce adenocarcinoma cells more often. In the other case follicular cervicitis was correctly diagnosed by the trained cytotechnologists but frequently misinterpreted by the students."}
{"id": "PMID:214985", "title": "Hepatoma development during long term follow-up period of liver cirrhosis.", "content": "An attempt was made to elucidate the pathogenesis of hepatoma. The material comprises 20 cases which were followed up more than 3 years after diagnosed liver cirrhosis and verified by autopsy. Hepatoma was found in 10 out of these 20 cases (50%). The follow-up period of these 10 cases with hepatoma was from 3 to 9.5 years (the mean value; 5.5 years). All 10 cases were not heavy drinkers, and showed liver cirrhosis of the mixed type by autopsy. HBsAG was positive in 6 out of 8 cases by RIA method (75%), and alpha-f was also detected in 5 of 7 cases by RIA method (70%). On the contrary, only 2 out of 10 cases without hepatoma were HBsAG positive (20%). The present results indicate that HBsAG positive liver cirrhosis of the mixed type is closely related to hepatoma in our country.", "contents": "Hepatoma development during long term follow-up period of liver cirrhosis. An attempt was made to elucidate the pathogenesis of hepatoma. The material comprises 20 cases which were followed up more than 3 years after diagnosed liver cirrhosis and verified by autopsy. Hepatoma was found in 10 out of these 20 cases (50%). The follow-up period of these 10 cases with hepatoma was from 3 to 9.5 years (the mean value; 5.5 years). All 10 cases were not heavy drinkers, and showed liver cirrhosis of the mixed type by autopsy. HBsAG was positive in 6 out of 8 cases by RIA method (75%), and alpha-f was also detected in 5 of 7 cases by RIA method (70%). On the contrary, only 2 out of 10 cases without hepatoma were HBsAG positive (20%). The present results indicate that HBsAG positive liver cirrhosis of the mixed type is closely related to hepatoma in our country."}
{"id": "PMID:214986", "title": "Computed tomography in hepatobiliary diseases.", "content": "Computed Tomography (CT) was introduced to detect lesions in 48 cases with various hepatobiliary disease. In 8 out of 11 cases with liver cell cancer, diagnosis were made by CT. A case was detected in early stage, the low density area was so small that it can be resected segmentally. In 7 out of 9 cases with metastatic liver cancer, multiple low densities were detected by C.T. Gallbladder cancers, which is known as diagnostic difficulty, were detected in five cases as low density in gallbladder area. CT has superiority to liver scintiscan, 1) CT can determine the tumor more exactly except for the diffuse type. 2) CT can be performed repeatedly without any risk and use of isotopic substances. 3) CT observes the transverse configuration of the organ, which could not be done in any conventional method.", "contents": "Computed tomography in hepatobiliary diseases. Computed Tomography (CT) was introduced to detect lesions in 48 cases with various hepatobiliary disease. In 8 out of 11 cases with liver cell cancer, diagnosis were made by CT. A case was detected in early stage, the low density area was so small that it can be resected segmentally. In 7 out of 9 cases with metastatic liver cancer, multiple low densities were detected by C.T. Gallbladder cancers, which is known as diagnostic difficulty, were detected in five cases as low density in gallbladder area. CT has superiority to liver scintiscan, 1) CT can determine the tumor more exactly except for the diffuse type. 2) CT can be performed repeatedly without any risk and use of isotopic substances. 3) CT observes the transverse configuration of the organ, which could not be done in any conventional method."}
{"id": "PMID:214983", "title": "Scan-guided fine needle aspiration biopsy in malignant hepatic disease.", "content": "The method of scan-guided fine needle aspiration biopsy of the liver is described, and the diagnostic value of this combined method in the diagnosis of malignant hepatic disease is evaluated in 83 confirmed cases, showing a specificity of 100% and a sensitivity of 94%. The combined method is compared to liver scanning alone and to Menghini biopsy. Different methods for the diagnosis of malignant hepatic disease are discussed, and it is concluded that scan-guided fine needle aspiration biopsy has a diagnostic value only obtainable otherwise by a combination of liver scanning and biopsy during laparoscopy. Cytologic features in the two most common tumor types in this study, i.e., metastatic colonic adenocarcinoma and hepatocarcinoma, are presented along with a brief discussion of the specificity of the cytologic diagnosis of hepatocarcinoma.", "contents": "Scan-guided fine needle aspiration biopsy in malignant hepatic disease. The method of scan-guided fine needle aspiration biopsy of the liver is described, and the diagnostic value of this combined method in the diagnosis of malignant hepatic disease is evaluated in 83 confirmed cases, showing a specificity of 100% and a sensitivity of 94%. The combined method is compared to liver scanning alone and to Menghini biopsy. Different methods for the diagnosis of malignant hepatic disease are discussed, and it is concluded that scan-guided fine needle aspiration biopsy has a diagnostic value only obtainable otherwise by a combination of liver scanning and biopsy during laparoscopy. Cytologic features in the two most common tumor types in this study, i.e., metastatic colonic adenocarcinoma and hepatocarcinoma, are presented along with a brief discussion of the specificity of the cytologic diagnosis of hepatocarcinoma."}
{"id": "PMID:214987", "title": "Hepatitis B virus infection and chronic liver disease in Taiwan.", "content": "Three hundred and eighty-five patients mostly with chronic liver diseases and 729 apparently healthy adults were studied for hepatitis B surface antigen (HBsAg) with reversed passive hemagglutination and antibody (anti-HBs) with passive hemagglutination. In healthy adults around 15% was HBsAg positive and in 45% was anti-HBs positive, estimating hepatitis B virus (HBV) infection in nearly two thirds of the population. The infection already occurred before adulthood. The prevalences of HBsAg were invariably over 80% in chronic hepatitis, cirrhosis and hepatocellular carcinoma (hepatoma) indicating an intimate relationship to HBV. On the contrary, the positive rates of anti-HBs in these diseases were far lower than those in healthy people and patients with other diseases, this is similar to the situation in chronic HBsAg carriers. The prevalence of HBsAg in hepatoma patients was unusually high, being 82.7% in contrast to 11.9% in patients with other malignancies. Not only hepatoma patients with cirrhosis but also those without cirrhosis were found to have high prevalence of HBsAg. The fact indicates an even more intimate relationship between hepatoma and HBV.", "contents": "Hepatitis B virus infection and chronic liver disease in Taiwan. Three hundred and eighty-five patients mostly with chronic liver diseases and 729 apparently healthy adults were studied for hepatitis B surface antigen (HBsAg) with reversed passive hemagglutination and antibody (anti-HBs) with passive hemagglutination. In healthy adults around 15% was HBsAg positive and in 45% was anti-HBs positive, estimating hepatitis B virus (HBV) infection in nearly two thirds of the population. The infection already occurred before adulthood. The prevalences of HBsAg were invariably over 80% in chronic hepatitis, cirrhosis and hepatocellular carcinoma (hepatoma) indicating an intimate relationship to HBV. On the contrary, the positive rates of anti-HBs in these diseases were far lower than those in healthy people and patients with other diseases, this is similar to the situation in chronic HBsAg carriers. The prevalence of HBsAg in hepatoma patients was unusually high, being 82.7% in contrast to 11.9% in patients with other malignancies. Not only hepatoma patients with cirrhosis but also those without cirrhosis were found to have high prevalence of HBsAg. The fact indicates an even more intimate relationship between hepatoma and HBV."}
{"id": "PMID:214984", "title": "Cytologic evaluation of experimental type 2 herpes simplex infection in mice.", "content": "The nature and frequency of cytopathologic changes in female mice genitally infected with type 2 herpes simplex virus have been investigated. The extent of virus infection in an individual mouse was assessed by a system of \"plus scoring\". Exfoliative cytology clearly provided a reliable evaluation of the extent of virus infection and a reliable prognostic index of mouse mortality. A composite index combining both cytologic and virologic information ('vircyt' value) was derived and shown to provide a convenient and precise prognostic index of mouse mortality.", "contents": "Cytologic evaluation of experimental type 2 herpes simplex infection in mice. The nature and frequency of cytopathologic changes in female mice genitally infected with type 2 herpes simplex virus have been investigated. The extent of virus infection in an individual mouse was assessed by a system of \"plus scoring\". Exfoliative cytology clearly provided a reliable evaluation of the extent of virus infection and a reliable prognostic index of mouse mortality. A composite index combining both cytologic and virologic information ('vircyt' value) was derived and shown to provide a convenient and precise prognostic index of mouse mortality."}
{"id": "PMID:214990", "title": "Reduced serum 1,25-(OH)2 vitamin D3 levels in prednisone-treated adolescents with systemic lupus erythematosus.", "content": "The serum levels of 1,25-(OH)2 vitamin D3 were assayed in samples from 12 adolescent patients with SLE. Subnormal levels were observed in 7 of these 12 patients. Low levels of the metabolically active polar metabolite of vitamin D3 may contribute to the development of osteopenia observed in this disease. The cumulative effects of the osteoporotic and anti vitamin D effects of long term steroid therapy in children with SLE may require the cautious administration of supplemental vitamin D.", "contents": "Reduced serum 1,25-(OH)2 vitamin D3 levels in prednisone-treated adolescents with systemic lupus erythematosus. The serum levels of 1,25-(OH)2 vitamin D3 were assayed in samples from 12 adolescent patients with SLE. Subnormal levels were observed in 7 of these 12 patients. Low levels of the metabolically active polar metabolite of vitamin D3 may contribute to the development of osteopenia observed in this disease. The cumulative effects of the osteoporotic and anti vitamin D effects of long term steroid therapy in children with SLE may require the cautious administration of supplemental vitamin D."}
{"id": "PMID:214991", "title": "A variant of the Klippel-Trenaunay-Weber syndrome with temporal lobe astrocytoma.", "content": "An 8-year-old boy with a variant of the Klippel-Trenaunay-Weber syndrome (KTW syndrome) is described. The hemangiomatous tissue located to the right half of his trunk and extremities was hypotrophic. On the same side, on his face and gingivae the tissue appeared hypertrophic and dental abnormalities were present. Moreover, the patient suffered from psychomotor epilepsy caused by a right-sided temporal astrocytoma. The connection between the KTW syndrome and the neurocutaneous syndromes is discussed.", "contents": "A variant of the Klippel-Trenaunay-Weber syndrome with temporal lobe astrocytoma. An 8-year-old boy with a variant of the Klippel-Trenaunay-Weber syndrome (KTW syndrome) is described. The hemangiomatous tissue located to the right half of his trunk and extremities was hypotrophic. On the same side, on his face and gingivae the tissue appeared hypertrophic and dental abnormalities were present. Moreover, the patient suffered from psychomotor epilepsy caused by a right-sided temporal astrocytoma. The connection between the KTW syndrome and the neurocutaneous syndromes is discussed."}
{"id": "PMID:214992", "title": "Prediction of adult height with various methods in Finnish children.", "content": "Successive height predictions were made by several methods for a group of healthy Finnish children (30 boys and 30 girls), examined annually at ages of 7 to 17 years (1st series) and for 7 boys aged 14 to 19 years with familial delayed growth and puberty (2nd series). The methods used were those of Bayley & Pinneau (BP), Walker (W), Tanner et al. (T) and RWT, and two simple principles: the relative height method (RH) which assumes constancy of height S.D.S. throughout growth, and the index of potential height (IPH) method which assumes constancy of height S.D.S. for bone age (BA). The predictions with RH, W and IPH were inaccurate. BP, T and RWT were for the 1st series as accurate as for the basic series of the respective methods, and none was superior to the others. The BA of average Finns was delayed as compared with the standards of Greulich-Pyle Atlas. When corrections were made for this delay, the IPH method gave predictions comparable in accuracy to BP, T or RWT. In the 2nd series prediction was more accurate with the corrected IPH, BP and RWT methods than with those using BA according to TW2RUS.", "contents": "Prediction of adult height with various methods in Finnish children. Successive height predictions were made by several methods for a group of healthy Finnish children (30 boys and 30 girls), examined annually at ages of 7 to 17 years (1st series) and for 7 boys aged 14 to 19 years with familial delayed growth and puberty (2nd series). The methods used were those of Bayley & Pinneau (BP), Walker (W), Tanner et al. (T) and RWT, and two simple principles: the relative height method (RH) which assumes constancy of height S.D.S. throughout growth, and the index of potential height (IPH) method which assumes constancy of height S.D.S. for bone age (BA). The predictions with RH, W and IPH were inaccurate. BP, T and RWT were for the 1st series as accurate as for the basic series of the respective methods, and none was superior to the others. The BA of average Finns was delayed as compared with the standards of Greulich-Pyle Atlas. When corrections were made for this delay, the IPH method gave predictions comparable in accuracy to BP, T or RWT. In the 2nd series prediction was more accurate with the corrected IPH, BP and RWT methods than with those using BA according to TW2RUS."}
{"id": "PMID:214993", "title": "Experimental mixed CNS infections in mice caused by three Ixodes ricinus transmitted Arboviruses.", "content": "Approximately 12-day-old mice were infected intracerebrally with tick-borne encephalitis (TBE) virus (strain Hypr), Unkuniemi virus (strain By E50) and Tribec virus, as single virus inoculations, coinfections with two or three viruses, and sequential infections with two or three viruses at 24-hour intervals. The effect of mixed infections on mortality, morbidity and average survival time was recorded. The main findings were that: 1. Some mixed infections with TBE and UUK viruses reduced the mortality and acute morbidity significantly as compared to single infections with each virus. The average survival times were lengthened. 2. Mixed infections with TBE and Tribec did not affect the 100% mortality of TBE. 3. Mixed infections with UUK and Tribec seemed to result in a cumulative effect of the two viruses. 4. With triple co-infections (TBE + Tribec + UUK simultaneously), the mortality and acute morbidity rates were reduced significantly as compared to TBE single infections. 5. Some of the mixed infections tended to result in chronic disease among the survivors.", "contents": "Experimental mixed CNS infections in mice caused by three Ixodes ricinus transmitted Arboviruses. Approximately 12-day-old mice were infected intracerebrally with tick-borne encephalitis (TBE) virus (strain Hypr), Unkuniemi virus (strain By E50) and Tribec virus, as single virus inoculations, coinfections with two or three viruses, and sequential infections with two or three viruses at 24-hour intervals. The effect of mixed infections on mortality, morbidity and average survival time was recorded. The main findings were that: 1. Some mixed infections with TBE and UUK viruses reduced the mortality and acute morbidity significantly as compared to single infections with each virus. The average survival times were lengthened. 2. Mixed infections with TBE and Tribec did not affect the 100% mortality of TBE. 3. Mixed infections with UUK and Tribec seemed to result in a cumulative effect of the two viruses. 4. With triple co-infections (TBE + Tribec + UUK simultaneously), the mortality and acute morbidity rates were reduced significantly as compared to TBE single infections. 5. Some of the mixed infections tended to result in chronic disease among the survivors."}
{"id": "PMID:214994", "title": "Effects of detergent formula chelating agents on the metabolism and toxicity of cadmium in mice.", "content": "Chelating agents like NTA (nitrilotriacetic acid) STPP (sodiumtripolyphosphate, Na5P3O10) and EDTA (ethylenediaminetetraacetic acid) are used as components of detergents. An increased toxicity of some metal compounds when combined with NTA has led to decreased use of this chelating agent in relation to STPP. In the present studies short-term and long-term effects of these chelating agents on cadmium toxicity in mice were investigated. I: In the short-term study, mice subcutaneously exposed to CdCl2 (3.2 mg Cd/kg b. wt.) in combination with STPP (32 mg/kg b. wt.) demonstrated a markedly higher mortality compared to animals given CdCl2 alone. This increase in mortality was similar to the one encountered when CdCl2 (3.2 mg Cd/kg b. wt.) and NTA (32 mg/kg b. wt.) were combined. Animals exposed subcutaneously to CdCl2 + STPP or CdCl2 + NTA showed histological evidence of liver necrosis 24 hrs after exposure not seen in animals given the same dose of CdCl2 alone and also had markedly lower cadmium concentrations in the livers compared to only Cd-exposed animals. II: In the long-term study, mice were exposed orally to CdSO4 (50p.p.m Cd) alone or in combination with STPP (500 p.p.m.), NTA (500 p.p.m.) or EDTA (50 p.p.m.) by continuous administration via the drinking water for 18 months. A decreased total excretion of urine proteins was seen in all Cd-treated animals irrespectively of the combination with various chelating agents. The conclusion of the present work was the NTA and STPP given by subcutaneous injection to mice markedly increased the toxicity of cadmium but that neither NTA, STPP nor EDTA given orally altered the toxicity of cadmium during a period of long-term exposure of 18 months.", "contents": "Effects of detergent formula chelating agents on the metabolism and toxicity of cadmium in mice. Chelating agents like NTA (nitrilotriacetic acid) STPP (sodiumtripolyphosphate, Na5P3O10) and EDTA (ethylenediaminetetraacetic acid) are used as components of detergents. An increased toxicity of some metal compounds when combined with NTA has led to decreased use of this chelating agent in relation to STPP. In the present studies short-term and long-term effects of these chelating agents on cadmium toxicity in mice were investigated. I: In the short-term study, mice subcutaneously exposed to CdCl2 (3.2 mg Cd/kg b. wt.) in combination with STPP (32 mg/kg b. wt.) demonstrated a markedly higher mortality compared to animals given CdCl2 alone. This increase in mortality was similar to the one encountered when CdCl2 (3.2 mg Cd/kg b. wt.) and NTA (32 mg/kg b. wt.) were combined. Animals exposed subcutaneously to CdCl2 + STPP or CdCl2 + NTA showed histological evidence of liver necrosis 24 hrs after exposure not seen in animals given the same dose of CdCl2 alone and also had markedly lower cadmium concentrations in the livers compared to only Cd-exposed animals. II: In the long-term study, mice were exposed orally to CdSO4 (50p.p.m Cd) alone or in combination with STPP (500 p.p.m.), NTA (500 p.p.m.) or EDTA (50 p.p.m.) by continuous administration via the drinking water for 18 months. A decreased total excretion of urine proteins was seen in all Cd-treated animals irrespectively of the combination with various chelating agents. The conclusion of the present work was the NTA and STPP given by subcutaneous injection to mice markedly increased the toxicity of cadmium but that neither NTA, STPP nor EDTA given orally altered the toxicity of cadmium during a period of long-term exposure of 18 months."}
{"id": "PMID:214995", "title": "X-radiation actions on the neuromuscular transmission.", "content": "The effects of high doses of X-radiation (100 kilorads) on the neuromuscular transmission of isolated sciatic nerve-sartorius muscle preparations of the frog, as evaluated by bioelectrical characteristics, were explored. Intracellular microelectrode recordings after X-irradiation showed that the resting, excitation and action potentials of nerve fibers approaching the synaptic terminal region of the motor end-plate became lessened, and also presented a slower velocity of impulse propagation, earlier than that observed in muscle cells. After forty minutes following the irradiation period, the neuromuscular transmission became blocked, although muscle fibers still responded to direct electrical stimulation. Records taken at the motor end-plate region of muscle cells, demonstrated the presence of postsynaptic miniature end-plate potentials (m.e.p.p.'s), the sequence of which fits closely into a random Poisson distribution. X-irradiation elicited an increase of the rate of m.e.p.p.'s and induced membrane changes over fine terminal nerve branches, leading into a failure to initiate and propagate action potentials. Only as time progressed, this nerve bioelectrical impairment was accompanied by a similar one in muscle cells, associated to the inability to develop contractile tension. The increase of m.e.p.p.'s frequency due to depolarization by a high K+ concentration, of presynaptic nerve membranes of control and irradiated preparations, was reversed by a high Mg+--Ca2+--free media. However, a concentration of Mg2+, which normally reduced quantal release of acetylcholine (ACh), without altering presynaptic nerve membrane potentials, failed to modify the spontaneous basal frequency of m.e.p.p.'s, both in irradiated and control preparations. The findings of the present study suggest that the presynaptic ACh synthesis, storage, and availability for ACh liberation are not early affected by X-rays, i.e. at a time when transmission from nerve to muscle had already failed. On the contrary, the most precocius membrane changes following X-irradiation, seem related to the mechanisms underlying nerve resting, excitation, and action potentials. The smallest presynaptic nerve terminal fibers close to the motor end-plate, are the most radiosensitive portion of the myoneural junction. Indeed, their bioelectric characteristics are early affected by X-rays, resulting in a failure to generate and propagate nerve impulses which lead to a blockade of neuromuscular transmission.", "contents": "X-radiation actions on the neuromuscular transmission. The effects of high doses of X-radiation (100 kilorads) on the neuromuscular transmission of isolated sciatic nerve-sartorius muscle preparations of the frog, as evaluated by bioelectrical characteristics, were explored. Intracellular microelectrode recordings after X-irradiation showed that the resting, excitation and action potentials of nerve fibers approaching the synaptic terminal region of the motor end-plate became lessened, and also presented a slower velocity of impulse propagation, earlier than that observed in muscle cells. After forty minutes following the irradiation period, the neuromuscular transmission became blocked, although muscle fibers still responded to direct electrical stimulation. Records taken at the motor end-plate region of muscle cells, demonstrated the presence of postsynaptic miniature end-plate potentials (m.e.p.p.'s), the sequence of which fits closely into a random Poisson distribution. X-irradiation elicited an increase of the rate of m.e.p.p.'s and induced membrane changes over fine terminal nerve branches, leading into a failure to initiate and propagate action potentials. Only as time progressed, this nerve bioelectrical impairment was accompanied by a similar one in muscle cells, associated to the inability to develop contractile tension. The increase of m.e.p.p.'s frequency due to depolarization by a high K+ concentration, of presynaptic nerve membranes of control and irradiated preparations, was reversed by a high Mg+--Ca2+--free media. However, a concentration of Mg2+, which normally reduced quantal release of acetylcholine (ACh), without altering presynaptic nerve membrane potentials, failed to modify the spontaneous basal frequency of m.e.p.p.'s, both in irradiated and control preparations. The findings of the present study suggest that the presynaptic ACh synthesis, storage, and availability for ACh liberation are not early affected by X-rays, i.e. at a time when transmission from nerve to muscle had already failed. On the contrary, the most precocius membrane changes following X-irradiation, seem related to the mechanisms underlying nerve resting, excitation, and action potentials. The smallest presynaptic nerve terminal fibers close to the motor end-plate, are the most radiosensitive portion of the myoneural junction. Indeed, their bioelectric characteristics are early affected by X-rays, resulting in a failure to generate and propagate nerve impulses which lead to a blockade of neuromuscular transmission."}
{"id": "PMID:214996", "title": "An improved procedure for purifying RNA tumor viruses from malignant tissue.", "content": "A convenient method for purifying RNA tumor viruses is described. Viruses banded in isopycnic gradients are contaminated with membranes that can be removed by velocity sedimentation in glycerol gradients. On sodium dodecyl sulfate (SDS) gel electrophoresis, the particles purified by these procedures from mouse mammary tumor tissue show protein profiles typical of those observed with virus purified from milk.", "contents": "An improved procedure for purifying RNA tumor viruses from malignant tissue. A convenient method for purifying RNA tumor viruses is described. Viruses banded in isopycnic gradients are contaminated with membranes that can be removed by velocity sedimentation in glycerol gradients. On sodium dodecyl sulfate (SDS) gel electrophoresis, the particles purified by these procedures from mouse mammary tumor tissue show protein profiles typical of those observed with virus purified from milk."}
{"id": "PMID:214997", "title": "Studies of the adrenergic reactivity in different regions of rabbit and rat oviduct.", "content": "Experiments are made to study the spontaneous contractions and the contractile response to noradrenaline of muscle strips isolated in longitudinal direction from the ampulla, isthmus and horn of the oviduct. Left oviduct of rats (in oestrus and dioestrus) and rabbits (in dioestrus) was used. In both rats and rabbits, all muscle strips including the ovarium manifest spontaneous contractions with highest frequency in the ovarium and ampulla, lower in the isthmus and lowest in the horn. Noradrenaline inhibits spontaneous contractions of strips in rat oviduct and ovarium. The inhibitory effect is manifested at lower noradrenaline concentration for the horn and isthmus (maximum effective concentration 3 X 10(-7) M in dioestrus and 3 X 10(-6) M in oestrus) compared with the ampulla and the ovarium (3 X 10(-6) M in dioestrus and 3 x 10(-5) in oestrus). Noradrenaline stimulates rabbit oviduct contractions . The stimulating response is manifested at lower noradrenaline concentration (1 X 10(-8) M minimum effective concentration) for the isthmus, higher for the horn (5 X 10(-7) M) and highest for the ampulla (5 X 10(-6) M). The presence of different alpha- and beta-adrenergic reactivities in the different areas of the oviduct is discussed.", "contents": "Studies of the adrenergic reactivity in different regions of rabbit and rat oviduct. Experiments are made to study the spontaneous contractions and the contractile response to noradrenaline of muscle strips isolated in longitudinal direction from the ampulla, isthmus and horn of the oviduct. Left oviduct of rats (in oestrus and dioestrus) and rabbits (in dioestrus) was used. In both rats and rabbits, all muscle strips including the ovarium manifest spontaneous contractions with highest frequency in the ovarium and ampulla, lower in the isthmus and lowest in the horn. Noradrenaline inhibits spontaneous contractions of strips in rat oviduct and ovarium. The inhibitory effect is manifested at lower noradrenaline concentration for the horn and isthmus (maximum effective concentration 3 X 10(-7) M in dioestrus and 3 X 10(-6) M in oestrus) compared with the ampulla and the ovarium (3 X 10(-6) M in dioestrus and 3 x 10(-5) in oestrus). Noradrenaline stimulates rabbit oviduct contractions . The stimulating response is manifested at lower noradrenaline concentration (1 X 10(-8) M minimum effective concentration) for the isthmus, higher for the horn (5 X 10(-7) M) and highest for the ampulla (5 X 10(-6) M). The presence of different alpha- and beta-adrenergic reactivities in the different areas of the oviduct is discussed."}
{"id": "PMID:214998", "title": "Adenosine and cyclic AMP in cerebral cortex of rats in hypoxia, status epilepticus and hypercapnia.", "content": "The influence of hypercapnia, hypoxia and status epilepticus on cerebral cortex concentrations of adenosine, adenine nucleotides and cyclic AMP was studied on lightly anaesthetized (70% N2O) and artificially ventilated rats. Neither hypercapnia (arterial PCO2 about 80 and about 300 mmHg) nor hypoxia (minimal values of 19 mmHg) altered tissue concentrations of AMP, cyclic AMP or adenosine. Bicuculline-induced status epilepticus was accompanied by increased concentrations of cyclic AMP but adenosine concentration did not change. Experiments with ischemia, and those in which tissue hypoxia was exaggerated by unilateral carotid artery ligation, showed that tissue adenosine concentrations were elevated only when AMP concentration rose. It is concluded that the marked increase in cerebral blood flow which occurs in hypoxia and status epilepticus is unrelated to changes in tissue adenosine concentration and that the increase in cyclic AMP during neuronal hyperactivity is triggered by other mechanisms than adenosine accumulation.", "contents": "Adenosine and cyclic AMP in cerebral cortex of rats in hypoxia, status epilepticus and hypercapnia. The influence of hypercapnia, hypoxia and status epilepticus on cerebral cortex concentrations of adenosine, adenine nucleotides and cyclic AMP was studied on lightly anaesthetized (70% N2O) and artificially ventilated rats. Neither hypercapnia (arterial PCO2 about 80 and about 300 mmHg) nor hypoxia (minimal values of 19 mmHg) altered tissue concentrations of AMP, cyclic AMP or adenosine. Bicuculline-induced status epilepticus was accompanied by increased concentrations of cyclic AMP but adenosine concentration did not change. Experiments with ischemia, and those in which tissue hypoxia was exaggerated by unilateral carotid artery ligation, showed that tissue adenosine concentrations were elevated only when AMP concentration rose. It is concluded that the marked increase in cerebral blood flow which occurs in hypoxia and status epilepticus is unrelated to changes in tissue adenosine concentration and that the increase in cyclic AMP during neuronal hyperactivity is triggered by other mechanisms than adenosine accumulation."}
{"id": "PMID:214999", "title": "Inhibition of acetylcholine release in guinea pig ileum by adenosine.", "content": "The effect of adenosine on cholinergic neuroeffector transmission was studied in the isolated guinea pig ileum. Adenosine caused a dose-dependent and inverse frequency-dependent inhibition of contraction responses to transmural nerve stimulation. Blockade of adrenergic neurotransmission did not alter the inhibitory effect of adenosine. Adenosine also inhibited contraction responses to serotonin, angiotensin and high potassium, but not the responses to acetylcholine, histamine or direct electrical stimulation of the smooth muscle cells. Adenosine had little effect on basal outflow of acetylcholine but inhibited markedly and reversibly the release of acetylcholine induced by nerve stimulation. Acetylcholine was determined with gas chromatography-mass spectrometry. The results provide direct evidence that adenosine inhibits cholinergic neuroeffector transmission in the gut by a prejunctional action on acetylcholine release. This may be of functional importance since adenine compounds are released during stimulation of intestinal nerves.", "contents": "Inhibition of acetylcholine release in guinea pig ileum by adenosine. The effect of adenosine on cholinergic neuroeffector transmission was studied in the isolated guinea pig ileum. Adenosine caused a dose-dependent and inverse frequency-dependent inhibition of contraction responses to transmural nerve stimulation. Blockade of adrenergic neurotransmission did not alter the inhibitory effect of adenosine. Adenosine also inhibited contraction responses to serotonin, angiotensin and high potassium, but not the responses to acetylcholine, histamine or direct electrical stimulation of the smooth muscle cells. Adenosine had little effect on basal outflow of acetylcholine but inhibited markedly and reversibly the release of acetylcholine induced by nerve stimulation. Acetylcholine was determined with gas chromatography-mass spectrometry. The results provide direct evidence that adenosine inhibits cholinergic neuroeffector transmission in the gut by a prejunctional action on acetylcholine release. This may be of functional importance since adenine compounds are released during stimulation of intestinal nerves."}
{"id": "PMID:215000", "title": "Histiocytosis X. III. Clinical value of serial biopsies.", "content": "In a retrospective review of sequential biopsies in 8 cases of histiocytosis X, 2 developed xanthomatous or fibrous lesions, 3 remained unchanged, whereas 3 developed malignant disease, one Hodgkin's disease and 2 malignant histiocytosis. A possible progression from benign, well differentiated to malignant histiocytic lesion is discussed, and the importance of achieving a microscopic diagnosis is emphasized.", "contents": "Histiocytosis X. III. Clinical value of serial biopsies. In a retrospective review of sequential biopsies in 8 cases of histiocytosis X, 2 developed xanthomatous or fibrous lesions, 3 remained unchanged, whereas 3 developed malignant disease, one Hodgkin's disease and 2 malignant histiocytosis. A possible progression from benign, well differentiated to malignant histiocytic lesion is discussed, and the importance of achieving a microscopic diagnosis is emphasized."}
{"id": "PMID:215001", "title": "Adenoid cystic carcinoma (cylindroma) in the head and neck. A clinical review of 82 cases.", "content": "A review of 82 cases of adenoid cystic carcinoma in the head and neck is given. Radical surgery was carried out in 33 patients and yielded the best long-term results. Radiation therapy was given to 43 patients for inoperable tumour, local recurrence or, postoperatively, for sub-clinical disease. It proved especially valuable in obtaining remissions from local recurrence.", "contents": "Adenoid cystic carcinoma (cylindroma) in the head and neck. A clinical review of 82 cases. A review of 82 cases of adenoid cystic carcinoma in the head and neck is given. Radical surgery was carried out in 33 patients and yielded the best long-term results. Radiation therapy was given to 43 patients for inoperable tumour, local recurrence or, postoperatively, for sub-clinical disease. It proved especially valuable in obtaining remissions from local recurrence."}
{"id": "PMID:215002", "title": "Malignant fibrous histiocytoma with skeletal involvement.", "content": "Malignant fibrous histiocytoma of soft part is rather common but malignant fibrous histiocytoma of the bone is rarely encountered clinically. Authors present five cases of malignant fibrous histiocytoma with skeletal involvement and discuss their clinical course, x-ray findings and histological features. This tumor has marked tendency for local recurrence and metastasis. Other bone tumors such as giant cell tumor, aneurysmal bone cyst, non ossifying fibroma, osteosarcoma, fibrosarcoma of bone and metastatic cancer can be excluded by several characteristic findings observed in x-rays as well as histopathological features. All information on the patient should be carefully analysed, because it is difficult to decide whether bone involvement is primary or secondary. Four out of five cases definitely originated within the bone.", "contents": "Malignant fibrous histiocytoma with skeletal involvement. Malignant fibrous histiocytoma of soft part is rather common but malignant fibrous histiocytoma of the bone is rarely encountered clinically. Authors present five cases of malignant fibrous histiocytoma with skeletal involvement and discuss their clinical course, x-ray findings and histological features. This tumor has marked tendency for local recurrence and metastasis. Other bone tumors such as giant cell tumor, aneurysmal bone cyst, non ossifying fibroma, osteosarcoma, fibrosarcoma of bone and metastatic cancer can be excluded by several characteristic findings observed in x-rays as well as histopathological features. All information on the patient should be carefully analysed, because it is difficult to decide whether bone involvement is primary or secondary. Four out of five cases definitely originated within the bone."}
{"id": "PMID:215003", "title": "Relations between the pulvinar-lateralis posterior complex of the thalamus and the hippocampus in wakefulness and sleep in cats.", "content": "Paucisynaptic connections between n. lateralis posterior (LP) and dorsal hippocampus (Hip) have been demonstrated in acute experiments. In the free moving cats, with chronic implanted electrodes on the neocortex, in LP, pulvinar (Pul), VA and VL nuclei of the thalamus and in the dorsal hippocampus (Hip), the theta waves recorded in LP, Pul and Hip were not of the same frequency and origin. In wakefulness and in slow-wave sleep, the theta waves were of 3.5-4 c/s and occurred exclusively or predominantly in Pul-LP, while in paradoxical sleep they were of 5-6 c/s, occurred' in Hip and invaded the Pul-LP. These two types of theta waves represent two distinct modalities of their organization and reflect the involvement of different mechanisms in the different phases of sleep.", "contents": "Relations between the pulvinar-lateralis posterior complex of the thalamus and the hippocampus in wakefulness and sleep in cats. Paucisynaptic connections between n. lateralis posterior (LP) and dorsal hippocampus (Hip) have been demonstrated in acute experiments. In the free moving cats, with chronic implanted electrodes on the neocortex, in LP, pulvinar (Pul), VA and VL nuclei of the thalamus and in the dorsal hippocampus (Hip), the theta waves recorded in LP, Pul and Hip were not of the same frequency and origin. In wakefulness and in slow-wave sleep, the theta waves were of 3.5-4 c/s and occurred exclusively or predominantly in Pul-LP, while in paradoxical sleep they were of 5-6 c/s, occurred' in Hip and invaded the Pul-LP. These two types of theta waves represent two distinct modalities of their organization and reflect the involvement of different mechanisms in the different phases of sleep."}
{"id": "PMID:215005", "title": "Selected animal models for systematic antiatherosclerotic drug development.", "content": "We have developed an integrated system for antiatherosclerosis drug development utilizing rats, SEA quail, and cynomolgus monkeys as animal models. In general, the way the system is presently functioning is that thousands of compounds per year are randomly screened for hypobeta- or hyperalphalipoproteinemic activity in rats, and hundreds of compounds per year are screened in SEA quail for antiatherosclerotic and hypocholesterolaric activity. A few selected compounds that have activity in both rats and quail are then tested for lipoprotein modifying activity in cynomolgus monkeys. Nontoxic compounds having very good lipoprotein modifying activity in the monkey will then be recommended for clinical trials in man. We do not anticipate that this battery of testing will guarantee activity in man, but are hoping that it will at least increase the probability for finding a truly effective antiatherosclerotic drug to control the human disease.", "contents": "Selected animal models for systematic antiatherosclerotic drug development. We have developed an integrated system for antiatherosclerosis drug development utilizing rats, SEA quail, and cynomolgus monkeys as animal models. In general, the way the system is presently functioning is that thousands of compounds per year are randomly screened for hypobeta- or hyperalphalipoproteinemic activity in rats, and hundreds of compounds per year are screened in SEA quail for antiatherosclerotic and hypocholesterolaric activity. A few selected compounds that have activity in both rats and quail are then tested for lipoprotein modifying activity in cynomolgus monkeys. Nontoxic compounds having very good lipoprotein modifying activity in the monkey will then be recommended for clinical trials in man. We do not anticipate that this battery of testing will guarantee activity in man, but are hoping that it will at least increase the probability for finding a truly effective antiatherosclerotic drug to control the human disease."}
{"id": "PMID:215009", "title": "Relative atherogenicity of different plasma lipoproteins.", "content": "Originally, data from the Framingham study appeared to show that serum lipoprotein fractions were no better in predicting coronary heart disease than the total serum cholesterol. More recently, the concentration of high density lipoprotein has been shown to exhibit a strong negative correlation with coronary heart disease, especially in the older age groups in which total serum cholesterol shows little or no correlation with clinical events. Biochemical mechanisms that might clarify the role of high density lipoprotein in atherogenesis are forthcoming. Another aspect of the lipoprotein-atherogenesis question pertains to the possible role of chylomicrons. Animal experiments show that cholesterol feeding is frequently accompanied by an increase in beta-migrating, very low density lipoproteins which appear to be chylomicron remnants. The atherogenic effect of serum low- and very low-density lipoproteins, including chylomicron remnants, appears to depend more on their contribution to the total cholesterol concentration than to their origin in liver versus intestines.", "contents": "Relative atherogenicity of different plasma lipoproteins. Originally, data from the Framingham study appeared to show that serum lipoprotein fractions were no better in predicting coronary heart disease than the total serum cholesterol. More recently, the concentration of high density lipoprotein has been shown to exhibit a strong negative correlation with coronary heart disease, especially in the older age groups in which total serum cholesterol shows little or no correlation with clinical events. Biochemical mechanisms that might clarify the role of high density lipoprotein in atherogenesis are forthcoming. Another aspect of the lipoprotein-atherogenesis question pertains to the possible role of chylomicrons. Animal experiments show that cholesterol feeding is frequently accompanied by an increase in beta-migrating, very low density lipoproteins which appear to be chylomicron remnants. The atherogenic effect of serum low- and very low-density lipoproteins, including chylomicron remnants, appears to depend more on their contribution to the total cholesterol concentration than to their origin in liver versus intestines."}
{"id": "PMID:215011", "title": "Results of a five-year study of the curative effect of double stranded ribonucleic acid in viral dermatoses and eye diseases.", "content": "Double stranded RNA obtained from non-permissive E. coli cells infected with f2-phage was tested in 5 hospitals in viral dermtoses such as herpes simplex recidivans, herpes zoster, male genikeratonconjunctivitis herpetica and conjunctivitis lignosa. The results of clinical tests indicate that the preparation of phage double stranded RNA applied topically is harmless for man and has, in the majority of cases, a beneficial effect in the disease. This conclusion was based on the judgment of physicians, opinion of patients expressed in a questionnaire, and, results of a double-blind experiment.", "contents": "Results of a five-year study of the curative effect of double stranded ribonucleic acid in viral dermatoses and eye diseases. Double stranded RNA obtained from non-permissive E. coli cells infected with f2-phage was tested in 5 hospitals in viral dermtoses such as herpes simplex recidivans, herpes zoster, male genikeratonconjunctivitis herpetica and conjunctivitis lignosa. The results of clinical tests indicate that the preparation of phage double stranded RNA applied topically is harmless for man and has, in the majority of cases, a beneficial effect in the disease. This conclusion was based on the judgment of physicians, opinion of patients expressed in a questionnaire, and, results of a double-blind experiment."}
{"id": "PMID:215013", "title": "Production of interferon in human cell cultures by a new, potent viral inducer.", "content": "A new discovered double-stranded RNA inducer of interferon, bluetongue virus (BTV), stimulates the production of large amounts of interferon in animals as well as in many types of mammalian cell cultures, including human leukocytes, and continuous cell lines. The exceptional pH lability of BTV and its lack of pathogenicity for man further recommend its use as an interferon inducer. Among several human cell lines tested, the most efficient producer of interferon was a continuous cell line designated HT-1376, derived from a bladder carcinoma. With infectious BTV as the inducer, the HT-1376 line produced more interferon per cell than did leukocytes; interferon yields ranged from 10,000 to 60,000 units per ml of crude, unconcentrated supernatant fluid. Noninfectious BTV, inactivated by ultraviolet irradiation, was as effective as infectious virions. The interferon produced in HT-1376 cells has physicochemical and antigenic properties resembling those of fibroblast interferon produced in diploid cells.", "contents": "Production of interferon in human cell cultures by a new, potent viral inducer. A new discovered double-stranded RNA inducer of interferon, bluetongue virus (BTV), stimulates the production of large amounts of interferon in animals as well as in many types of mammalian cell cultures, including human leukocytes, and continuous cell lines. The exceptional pH lability of BTV and its lack of pathogenicity for man further recommend its use as an interferon inducer. Among several human cell lines tested, the most efficient producer of interferon was a continuous cell line designated HT-1376, derived from a bladder carcinoma. With infectious BTV as the inducer, the HT-1376 line produced more interferon per cell than did leukocytes; interferon yields ranged from 10,000 to 60,000 units per ml of crude, unconcentrated supernatant fluid. Noninfectious BTV, inactivated by ultraviolet irradiation, was as effective as infectious virions. The interferon produced in HT-1376 cells has physicochemical and antigenic properties resembling those of fibroblast interferon produced in diploid cells."}
{"id": "PMID:215015", "title": "Membrane alterations following interferon treatment.", "content": "Interferon treatment appears to induce a number of changes in the plasma membrane of uninfected cells. Interferon treatment altered the surface exposure of gangliosides of both Ly and KB cell membranes. The differences were found in the amount and pattern of incorporation of tritium after galactose oxidase treatment. In AKR,C- (AKR-2B) mouse cells, not only was there an apparent increase in the number of intramembranous particles in response to treatment with interferon but also the kinetics of the increase followed that of the establishment of the antiviral activity. The buoyant density of plasma membrane was also found to be significantly increased in interferon-treated cells. Moloney murine leukemia virus produced in interferon-treated mouse thymus and bone marrow cells had a high particle to infectivity ration. This virus contained a prominent glycoprotein with a molecular weight of about 85,000. This large glycoprotein was only a very minor component of Moloney leukemia virus produced in control TB cells and might be an uncleaved precursor to gp 69-71.", "contents": "Membrane alterations following interferon treatment. Interferon treatment appears to induce a number of changes in the plasma membrane of uninfected cells. Interferon treatment altered the surface exposure of gangliosides of both Ly and KB cell membranes. The differences were found in the amount and pattern of incorporation of tritium after galactose oxidase treatment. In AKR,C- (AKR-2B) mouse cells, not only was there an apparent increase in the number of intramembranous particles in response to treatment with interferon but also the kinetics of the increase followed that of the establishment of the antiviral activity. The buoyant density of plasma membrane was also found to be significantly increased in interferon-treated cells. Moloney murine leukemia virus produced in interferon-treated mouse thymus and bone marrow cells had a high particle to infectivity ration. This virus contained a prominent glycoprotein with a molecular weight of about 85,000. This large glycoprotein was only a very minor component of Moloney leukemia virus produced in control TB cells and might be an uncleaved precursor to gp 69-71."}
{"id": "PMID:215019", "title": "Oat cell carcinoma manifesting as a bronchocele.", "content": "Three cases of oat cell carcinoma appearing as a bronchocele on the chest radiograph are described. A bronchocele as the major radiologic manifestation of oat cell carcinoma has not been emphasized previously. Such a bronchocele may be filled with neoplastic cells rather than only inspissated mucus. Needle aspiration biopsy was definitive in two of the cases when conventional diagnostic methods failed.", "contents": "Oat cell carcinoma manifesting as a bronchocele. Three cases of oat cell carcinoma appearing as a bronchocele on the chest radiograph are described. A bronchocele as the major radiologic manifestation of oat cell carcinoma has not been emphasized previously. Such a bronchocele may be filled with neoplastic cells rather than only inspissated mucus. Needle aspiration biopsy was definitive in two of the cases when conventional diagnostic methods failed."}
{"id": "PMID:215020", "title": "Antrochoanal polyps.", "content": "The antrochoanal polyp, a benign solitary polypoid lesion, usually arises in a maxillary sinus, opacifying and enlarging the sinus cavity without bone destruction. It passes through the ostium of the sinus into the choana, and from there into the posterior nasopharynx. The soft tissue mass does not erode or destroy contiguous soft tissue or bony structures. In this sequence of events, its radiologic findings are characteristic. Five case reports are presented, and the differential diagnosis is discussed.", "contents": "Antrochoanal polyps. The antrochoanal polyp, a benign solitary polypoid lesion, usually arises in a maxillary sinus, opacifying and enlarging the sinus cavity without bone destruction. It passes through the ostium of the sinus into the choana, and from there into the posterior nasopharynx. The soft tissue mass does not erode or destroy contiguous soft tissue or bony structures. In this sequence of events, its radiologic findings are characteristic. Five case reports are presented, and the differential diagnosis is discussed."}
{"id": "PMID:215021", "title": "Hepatocellular carcinoma: clinical and angiographic findings and predictability for surgical resection.", "content": "Demographic, clinical, and angiographic data were reviewed for 63 consecutive patients with hepatocellular carcinoma. Angiography remains the critical examination in determining extent of disease and potential surgical cure. Angiographic findings were correlated with surgical or autopsy findings for 26 of the patients. The absence of venous invasion and lack of involvement of at least one hepatic segment favor resectability. Selective hepatic injections and oblique views accurately answered these questions in more than 80% of our patients. Pitfalls to angiographic accuracy include vascular invasion by very small tumor masses, hypovascular or diffuse hepatocellular carcinomas, metastatic disease, and involvement of the left lobe.", "contents": "Hepatocellular carcinoma: clinical and angiographic findings and predictability for surgical resection. Demographic, clinical, and angiographic data were reviewed for 63 consecutive patients with hepatocellular carcinoma. Angiography remains the critical examination in determining extent of disease and potential surgical cure. Angiographic findings were correlated with surgical or autopsy findings for 26 of the patients. The absence of venous invasion and lack of involvement of at least one hepatic segment favor resectability. Selective hepatic injections and oblique views accurately answered these questions in more than 80% of our patients. Pitfalls to angiographic accuracy include vascular invasion by very small tumor masses, hypovascular or diffuse hepatocellular carcinomas, metastatic disease, and involvement of the left lobe."}
{"id": "PMID:215024", "title": "Comparison of a sodium chloride aerosol filter test method to silica-dust and silica-mist filter test methods.", "content": "A LASL-developed sodium chloride aerosol filter penetration test has been compared to the silica-dust and silica-mist tests used by NIOSH for respirator approval testing. Filter discs were made from two types of resin impregnated electrostatic felt filter materials and tested at LASL for resistance to air flow and sodium chloride aerosol penetration. Sets of these filters were sent to four respirator manufacturing companies, where silica-dust and silica-mist penetration tests were performed. One set of filters was sent to NIOSH Division of Physical Sciences and Engineering in Cincinnati where sodium chloride aerosol penetration tests were performed by NIOSH personnel.", "contents": "Comparison of a sodium chloride aerosol filter test method to silica-dust and silica-mist filter test methods. A LASL-developed sodium chloride aerosol filter penetration test has been compared to the silica-dust and silica-mist tests used by NIOSH for respirator approval testing. Filter discs were made from two types of resin impregnated electrostatic felt filter materials and tested at LASL for resistance to air flow and sodium chloride aerosol penetration. Sets of these filters were sent to four respirator manufacturing companies, where silica-dust and silica-mist penetration tests were performed. One set of filters was sent to NIOSH Division of Physical Sciences and Engineering in Cincinnati where sodium chloride aerosol penetration tests were performed by NIOSH personnel."}
{"id": "PMID:215026", "title": "Two and three dimensional display of myocardial ischemic \"border zone\" in dogs.", "content": "It is intuitively apparent that the ultimate fate of reversibly damaged, peri-ischemic \"border zone\" tissue should relate to individual patient survival. The purpose of this study was: (1) to describe a technique of assessing the adequacy of epicardial and myocardial oxygenation, and (2) to examine the extent and character of the peri-ischemic \"border zone\" in the dog after coronary arterial ligation. A diagonal branch of the left anterior descending coronary artery was ligated in four anesthetized open chest, neurohormonally intact dogs. The same diagonal coronary artery was ligated in six isolated perfused canine heart preparations in which coronary partial pressures of oxygen and carbon dioxide, pH, blood flow and temperature were fixed. The ischemic zones were rapidly frozen and reduced nicotinamide adenine dinucleotide (NADH) fluorescence photographs were taken of the epicardium and at 0.5 mm depths into the myocardium. The distinction between perfused and ischemic myocardium is not apparent with the naked eye or natural light photography. Epicardial and myocardial oxidation-reduction status is well seen with NADH fluorophotography. In both the intact and perfused heart preparations the NADH-fluorescent (ischemic) border is jagged along all edges. Islands of perfused nonfluorescent tissue appear within the ischemic border. The transition between NADH-fluorescent ischemic cells and adjacent non-fluorescent tissue is less than 0.1 mm. The ischemic border is narrow. The distance between homogeneously NADH-fluorescent tissue and homogeneously nonfluorescent tissue (across the zone of island normoxia or microheterogeneity) may be as wide as 6 to 8 mm.", "contents": "Two and three dimensional display of myocardial ischemic \"border zone\" in dogs. It is intuitively apparent that the ultimate fate of reversibly damaged, peri-ischemic \"border zone\" tissue should relate to individual patient survival. The purpose of this study was: (1) to describe a technique of assessing the adequacy of epicardial and myocardial oxygenation, and (2) to examine the extent and character of the peri-ischemic \"border zone\" in the dog after coronary arterial ligation. A diagonal branch of the left anterior descending coronary artery was ligated in four anesthetized open chest, neurohormonally intact dogs. The same diagonal coronary artery was ligated in six isolated perfused canine heart preparations in which coronary partial pressures of oxygen and carbon dioxide, pH, blood flow and temperature were fixed. The ischemic zones were rapidly frozen and reduced nicotinamide adenine dinucleotide (NADH) fluorescence photographs were taken of the epicardium and at 0.5 mm depths into the myocardium. The distinction between perfused and ischemic myocardium is not apparent with the naked eye or natural light photography. Epicardial and myocardial oxidation-reduction status is well seen with NADH fluorophotography. In both the intact and perfused heart preparations the NADH-fluorescent (ischemic) border is jagged along all edges. Islands of perfused nonfluorescent tissue appear within the ischemic border. The transition between NADH-fluorescent ischemic cells and adjacent non-fluorescent tissue is less than 0.1 mm. The ischemic border is narrow. The distance between homogeneously NADH-fluorescent tissue and homogeneously nonfluorescent tissue (across the zone of island normoxia or microheterogeneity) may be as wide as 6 to 8 mm."}
{"id": "PMID:215027", "title": "The influence of dietary mackerel oil on the condition of organs and on blood lipid composition in the young growing pig.", "content": "A feeding experiment was carried out in which piglets were fed to a diet enriched with either mackerel oil or olive oil. The oil consumption amounted to about 100 g per animal per day. The aim of this experiment was to study the effect of feeding high amounts of fish oil rich in polyunsaturated and long-chain monoenoic acids in order to determine if any morbid changes occurred in the animals as a result of this addition. The piglets fed olive oil served as controls. After 4 weeks, blood hemoglobin, plasma glucose, and serum triglycerides were significantly lower in the mackerel oil group as compared with the control group. There was no difference in serum cholesterol and serum lipid composition. Very low density lipoproteins were lower in the mackerel oil group. The fatty acid composition of blood serum, heart muscle, and liver showed considerable differences, omega3 acids being higher and both omega6 and omega9 acids being lower in the mackerel oil group than in the control group. Some increase in the amount of triglycerides in the heart muscle was observed in the mackerel oil group. Some characteristics of \"yellow fat disease\" developed in the mackerel oil group. This type of vitamin E deficiency seems to be the result of the considerable amount of omega3 fatty acids present in the mackerel oil. No clinical symptoms due to ingestion of long-chain monoenoic acids were observed.", "contents": "The influence of dietary mackerel oil on the condition of organs and on blood lipid composition in the young growing pig. A feeding experiment was carried out in which piglets were fed to a diet enriched with either mackerel oil or olive oil. The oil consumption amounted to about 100 g per animal per day. The aim of this experiment was to study the effect of feeding high amounts of fish oil rich in polyunsaturated and long-chain monoenoic acids in order to determine if any morbid changes occurred in the animals as a result of this addition. The piglets fed olive oil served as controls. After 4 weeks, blood hemoglobin, plasma glucose, and serum triglycerides were significantly lower in the mackerel oil group as compared with the control group. There was no difference in serum cholesterol and serum lipid composition. Very low density lipoproteins were lower in the mackerel oil group. The fatty acid composition of blood serum, heart muscle, and liver showed considerable differences, omega3 acids being higher and both omega6 and omega9 acids being lower in the mackerel oil group than in the control group. Some increase in the amount of triglycerides in the heart muscle was observed in the mackerel oil group. Some characteristics of \"yellow fat disease\" developed in the mackerel oil group. This type of vitamin E deficiency seems to be the result of the considerable amount of omega3 fatty acids present in the mackerel oil. No clinical symptoms due to ingestion of long-chain monoenoic acids were observed."}
{"id": "PMID:215029", "title": "Malignant mixed tumor of the salivary-gland type, primary in the prostate.", "content": "A previously undescribed malignant mixed tumor arising in the prostate of a 72-year-old man is herein presented. Clinically, it was manifested by slowly progressing urinary frequency and urgency, as well as by intense pain. The total serum acid phosphatase value and the prostatic fraction were within normal limits. Six months after prostatectomy the patient died, with local recurrence and roentgenologic evidence of a single pulmonary metastasis. Both light-microscopic and electron-microscopic examination showed features similar to those of a malignant mixed tumor of the salivary gland. These findings suggest that this tumor originated in seromucinous ectopic glands. The important factor in its recognition is that it is not hormone-dependent.", "contents": "Malignant mixed tumor of the salivary-gland type, primary in the prostate. A previously undescribed malignant mixed tumor arising in the prostate of a 72-year-old man is herein presented. Clinically, it was manifested by slowly progressing urinary frequency and urgency, as well as by intense pain. The total serum acid phosphatase value and the prostatic fraction were within normal limits. Six months after prostatectomy the patient died, with local recurrence and roentgenologic evidence of a single pulmonary metastasis. Both light-microscopic and electron-microscopic examination showed features similar to those of a malignant mixed tumor of the salivary gland. These findings suggest that this tumor originated in seromucinous ectopic glands. The important factor in its recognition is that it is not hormone-dependent."}
{"id": "PMID:215030", "title": "Hypoglycorrhachia and coxsackie B3 meningoencephalitis.", "content": "The case of a 3-week-old infant with Coxsackie B3 meningoencephalitis is discussed. Hypoglycorrhachia and neutrophils in the cerebrospinal fluid characterized the first ten days of her illness. Coxsackie B3 should be added to the list of enteroviruses that can cause hypoglycorrhachia during infections of the central nervous system in children.", "contents": "Hypoglycorrhachia and coxsackie B3 meningoencephalitis. The case of a 3-week-old infant with Coxsackie B3 meningoencephalitis is discussed. Hypoglycorrhachia and neutrophils in the cerebrospinal fluid characterized the first ten days of her illness. Coxsackie B3 should be added to the list of enteroviruses that can cause hypoglycorrhachia during infections of the central nervous system in children."}
{"id": "PMID:215032", "title": "Sinking pre-beta lipoprotein and coronary heart disease in Japanese-American men in Hawaii.", "content": "A \"sinking\" pre-beta lipoprotein was sought in a probability sample of 1854, 50--72-year-old men of Japanese ancestry in Honolulu by ultracentrifugation of plasma and electrophoresis of the bottom fraction (density greater than 1.006) in agarose. A definite electrophoretic band was found in 5.6% of the men and a trace band was found in 4.6% of them. The frequency of such a band increased with age and decreased with adiposity. The relative risk for coronary heart disease, based on prevalence cases was found to be 1.7 in men with a definite band, and 1.4 in those with a trace band, when compared to men without. This association could not be explained by the higher low density lipoprotein levels in men with trace or definite bands. These data are consistent with previous reports suggesting that the Lp antigen (for which a sinking pre-beta lipoprotein is probably an insensitive marker) is associated with coronary disease.", "contents": "Sinking pre-beta lipoprotein and coronary heart disease in Japanese-American men in Hawaii. A \"sinking\" pre-beta lipoprotein was sought in a probability sample of 1854, 50--72-year-old men of Japanese ancestry in Honolulu by ultracentrifugation of plasma and electrophoresis of the bottom fraction (density greater than 1.006) in agarose. A definite electrophoretic band was found in 5.6% of the men and a trace band was found in 4.6% of them. The frequency of such a band increased with age and decreased with adiposity. The relative risk for coronary heart disease, based on prevalence cases was found to be 1.7 in men with a definite band, and 1.4 in those with a trace band, when compared to men without. This association could not be explained by the higher low density lipoprotein levels in men with trace or definite bands. These data are consistent with previous reports suggesting that the Lp antigen (for which a sinking pre-beta lipoprotein is probably an insensitive marker) is associated with coronary disease."}
{"id": "PMID:215034", "title": "Na-K pump and Na-K-ATPase: disparity of their temperature sensitivity.", "content": "As previously observed in red blood cells, ouabain-sensitive K influx of kidney cells grown in culture for 3 days was much less inhibited by cooling that Na-K-ATPase of the same cells. (At 5 degrees C K influx was 9.7% of that at 38 degrees C, Na-K-ATPase, 1--2%.) Resealed ghosts of erythrocytes of ground squirrels were made containing 24Na and ATP, and the Na efflux and ATP hydrolysis were measured simultaneously. Under these conditions there was no difference in the reduction of activity with cooling, and the amount of reduction was close to that of active K transport in intact cells. The high sensitivity to temperature, characteristic of broken membranes, could not be induced in intact cells or resealed ghosts by eliminating either the Na/K gradient or the ATP gradient nor by chelation of cellular and extracellular Ca. It could not be eliminated in broken membranes by protection with ATP or Mg. Structural reorganization of membrane during lysis may cause the increase in temperature sensitivity of Na-K-ATPase.", "contents": "Na-K pump and Na-K-ATPase: disparity of their temperature sensitivity. As previously observed in red blood cells, ouabain-sensitive K influx of kidney cells grown in culture for 3 days was much less inhibited by cooling that Na-K-ATPase of the same cells. (At 5 degrees C K influx was 9.7% of that at 38 degrees C, Na-K-ATPase, 1--2%.) Resealed ghosts of erythrocytes of ground squirrels were made containing 24Na and ATP, and the Na efflux and ATP hydrolysis were measured simultaneously. Under these conditions there was no difference in the reduction of activity with cooling, and the amount of reduction was close to that of active K transport in intact cells. The high sensitivity to temperature, characteristic of broken membranes, could not be induced in intact cells or resealed ghosts by eliminating either the Na/K gradient or the ATP gradient nor by chelation of cellular and extracellular Ca. It could not be eliminated in broken membranes by protection with ATP or Mg. Structural reorganization of membrane during lysis may cause the increase in temperature sensitivity of Na-K-ATPase."}
{"id": "PMID:215035", "title": "Evaluation of oxidative phosphorylation in hearts from euthyroid, hypothyroid, and hyperthyroid rats.", "content": "The energy relationships between cytosolic and mitochondrial metabolism were studied in the hearts from euthyroid, hypothyroid, and hyperthyroid rats. Isolated mitochondria showed high respiratory control ratios and impermeability to exogenous NADH. Hypo- and hyperthyroidism, respectively, resulted in lower and higher contents of both cytochromes per mitochondrion and mitochondrial protein per gram of wet weight of heart without changes in the ratio of cytochrome c to cytochrome aa3. In isolated perfused heart, the hyperthyroid state led to an increase in work rate and thereby an elevation of Vo2, which resulted in an increase oxidation-reduction turnover number for the cytochromes. An agreement was found between [ATP]/[ADP][Pi] of cytosolic free adenine nucleotides and the value calculated from a mathematical model of mitochondrial respiration. This implies that mitochondrial respiration is controlled at the cytochrome oxidase reaction and that oxidative phosphorylation in intact tissue is tightly coupled irrespective of thyroid state. It is concluded that thyroid hormone causes an increase in the mitochondrial mass, mitochondrial cytochrome content, and respiratory rate, and consequently expands the capacity of oxidative metabolism without an uncoupling effect on oxidative phosphorylation.", "contents": "Evaluation of oxidative phosphorylation in hearts from euthyroid, hypothyroid, and hyperthyroid rats. The energy relationships between cytosolic and mitochondrial metabolism were studied in the hearts from euthyroid, hypothyroid, and hyperthyroid rats. Isolated mitochondria showed high respiratory control ratios and impermeability to exogenous NADH. Hypo- and hyperthyroidism, respectively, resulted in lower and higher contents of both cytochromes per mitochondrion and mitochondrial protein per gram of wet weight of heart without changes in the ratio of cytochrome c to cytochrome aa3. In isolated perfused heart, the hyperthyroid state led to an increase in work rate and thereby an elevation of Vo2, which resulted in an increase oxidation-reduction turnover number for the cytochromes. An agreement was found between [ATP]/[ADP][Pi] of cytosolic free adenine nucleotides and the value calculated from a mathematical model of mitochondrial respiration. This implies that mitochondrial respiration is controlled at the cytochrome oxidase reaction and that oxidative phosphorylation in intact tissue is tightly coupled irrespective of thyroid state. It is concluded that thyroid hormone causes an increase in the mitochondrial mass, mitochondrial cytochrome content, and respiratory rate, and consequently expands the capacity of oxidative metabolism without an uncoupling effect on oxidative phosphorylation."}
{"id": "PMID:215036", "title": "Insulin release, cGMP, cAMP, and membrane potential in acetylcholine-stimulated islets.", "content": "Acetylcholine potentiated the glucose-induced insulin release from microdissected mouse islets of Langerhans but had no effect on basal insulin release. Significant potentiation was obtained with 0.1 micron acetylcholine in the presence of 10 micron eserine and with 1 micron or more acetylcholine in the absence of a choline esterase inhibitor. Carbamylcholine, too, potentiated insulin release. Potentiation was blocked by methylatropine, whereas methylatropine alone had no effect on insulin release. Acetylcholine or carbamylcholine (5-500 micron) had no obvious effect on cyclic GMP or cyclic AMP in the islets. In the presence of 11.1 mM D-glucose, the membrane potential of beta-cells oscillated slowly between a polarized silent state of -50 to -55 mV and a depolarized active state of -33 to -39 mV, at which a fast spike activity occurred. Acetylcholine made the potential stay at the plateau and induced a continuous spike activity pattern. Atropine inhibited the electrical effects of acetylcholine but not those of glucose alone. It is suggested that cholinergic potentiation of insulin release is mediated by changes of transmembrane ionic fluxes, probably without the intervention of cyclic GMP or cyclic AMP.", "contents": "Insulin release, cGMP, cAMP, and membrane potential in acetylcholine-stimulated islets. Acetylcholine potentiated the glucose-induced insulin release from microdissected mouse islets of Langerhans but had no effect on basal insulin release. Significant potentiation was obtained with 0.1 micron acetylcholine in the presence of 10 micron eserine and with 1 micron or more acetylcholine in the absence of a choline esterase inhibitor. Carbamylcholine, too, potentiated insulin release. Potentiation was blocked by methylatropine, whereas methylatropine alone had no effect on insulin release. Acetylcholine or carbamylcholine (5-500 micron) had no obvious effect on cyclic GMP or cyclic AMP in the islets. In the presence of 11.1 mM D-glucose, the membrane potential of beta-cells oscillated slowly between a polarized silent state of -50 to -55 mV and a depolarized active state of -33 to -39 mV, at which a fast spike activity occurred. Acetylcholine made the potential stay at the plateau and induced a continuous spike activity pattern. Atropine inhibited the electrical effects of acetylcholine but not those of glucose alone. It is suggested that cholinergic potentiation of insulin release is mediated by changes of transmembrane ionic fluxes, probably without the intervention of cyclic GMP or cyclic AMP."}
{"id": "PMID:215033", "title": "Hyperlipidemia and myocardial infarction among 118 patients with polycythemia vera.", "content": "Hyperlipidemia was reported among 46 of 118 polycythemia vera patients as compared to a control group of 115 healthy subjects in whom hyperlipidemia was reported in 20. Among the 46 hyperlipidemic patients with polycythemia vera 14 had a myocardial infarction, while among the other 72 nonhyperlipidemic polycythemia vera patients myocardial infarction occurred amont 17. Since repeated phlebotomies may induce hyperlipidemia, this form of treatment of polycythemia vera may be potentially dangerous in already hyperlipidemic polycythemia vera patients.", "contents": "Hyperlipidemia and myocardial infarction among 118 patients with polycythemia vera. Hyperlipidemia was reported among 46 of 118 polycythemia vera patients as compared to a control group of 115 healthy subjects in whom hyperlipidemia was reported in 20. Among the 46 hyperlipidemic patients with polycythemia vera 14 had a myocardial infarction, while among the other 72 nonhyperlipidemic polycythemia vera patients myocardial infarction occurred amont 17. Since repeated phlebotomies may induce hyperlipidemia, this form of treatment of polycythemia vera may be potentially dangerous in already hyperlipidemic polycythemia vera patients."}
{"id": "PMID:215038", "title": "Principles of nephron differentiation.", "content": "Differentiation of cell function should be studied in homogeneous cell populations. The differentiating mammalian kidney is a thoroughly heterogeneous organ. Consequently, the single epithelial segment was studied in situ and, particularly, by in vitro analysis of physical, chemical, and ultrastructural phenomena in perfused and nonperfused dissected nephrons. The changes of hydraulic permeability in the proximal nephron appear to be important in utilizing extracellular forces for absorption, since cellular transport is restricted by low basolateral membrane area and by ion pump sites (Na+-K+-ATPase). Salt transport in the diluting segment, by contrast, changes at constant osmotic permeability and at increasing ion concentration gradients across the epithelium. Extracellular volume and osmotic homeostasis in the neonate testify to the competence of organ function, although cell structure and function differentiate. In the future, interactions between nephron cell functions will be studied by altering the natural sequence of phenomena during differentiation.", "contents": "Principles of nephron differentiation. Differentiation of cell function should be studied in homogeneous cell populations. The differentiating mammalian kidney is a thoroughly heterogeneous organ. Consequently, the single epithelial segment was studied in situ and, particularly, by in vitro analysis of physical, chemical, and ultrastructural phenomena in perfused and nonperfused dissected nephrons. The changes of hydraulic permeability in the proximal nephron appear to be important in utilizing extracellular forces for absorption, since cellular transport is restricted by low basolateral membrane area and by ion pump sites (Na+-K+-ATPase). Salt transport in the diluting segment, by contrast, changes at constant osmotic permeability and at increasing ion concentration gradients across the epithelium. Extracellular volume and osmotic homeostasis in the neonate testify to the competence of organ function, although cell structure and function differentiate. In the future, interactions between nephron cell functions will be studied by altering the natural sequence of phenomena during differentiation."}
{"id": "PMID:215039", "title": "Effect of ouabain and colloid osmotic pressure on renal tubule cell volume.", "content": "Proximal renal tubule cell volume increases in ouabain but cell swelling is limited by the tubule basement membrane (TBM) and the colloid osmotic pressure from the bath protein. We compared the effect of ouabain, external protein concentration, and TBM on cell volume of proximal convoluted (PCT), proximal straight (PST), and cortical collecting tubules (CCT). We blocked active solute transport with ouabain and evaluated cell size by measuring the outer diameter of nonperfused tubules. Proximal tubules in ouabain swelled 35-40% in isoncotic medium and 20-25% further in hyponcotic medium (0.3 g/100 ml albumin), but PCT swelled faster than PST. The CCT swelled minimally in similar mediums, indicating pronounced heterogeneity in the response of cortical nephron segments to ouabain. In the presence of ouabain, all tubules swelled extensively when we removed the TBM with collagenase. In the hyponcotic medium fluid flux across the peritubular membrane was 0.081, 0.049, and 0.030 nl/min per mm tubule length for PCT, PST, and CCT, respectively. The rates of fluid flux in PCT and PST were proportional to estimates of the respective basolateral surface areas. We suggest that differences in swelling rates between proximal segments reflect variations in surface area rather than intrinsic peritubular membrane permeability to solute and water.", "contents": "Effect of ouabain and colloid osmotic pressure on renal tubule cell volume. Proximal renal tubule cell volume increases in ouabain but cell swelling is limited by the tubule basement membrane (TBM) and the colloid osmotic pressure from the bath protein. We compared the effect of ouabain, external protein concentration, and TBM on cell volume of proximal convoluted (PCT), proximal straight (PST), and cortical collecting tubules (CCT). We blocked active solute transport with ouabain and evaluated cell size by measuring the outer diameter of nonperfused tubules. Proximal tubules in ouabain swelled 35-40% in isoncotic medium and 20-25% further in hyponcotic medium (0.3 g/100 ml albumin), but PCT swelled faster than PST. The CCT swelled minimally in similar mediums, indicating pronounced heterogeneity in the response of cortical nephron segments to ouabain. In the presence of ouabain, all tubules swelled extensively when we removed the TBM with collagenase. In the hyponcotic medium fluid flux across the peritubular membrane was 0.081, 0.049, and 0.030 nl/min per mm tubule length for PCT, PST, and CCT, respectively. The rates of fluid flux in PCT and PST were proportional to estimates of the respective basolateral surface areas. We suggest that differences in swelling rates between proximal segments reflect variations in surface area rather than intrinsic peritubular membrane permeability to solute and water."}
{"id": "PMID:215040", "title": "Nycthemeral rhythm in adrenal responsiveness to ACTH.", "content": "Adrenal adenosine 3',5'-cyclic monophosphate (cAMP) and corticosterone responses to exogenous ACTH were found to be about 2.5 times greater in the evening (at lights off) than in the morning (at lights on) in rats. The rhythm in adrenal responsiveness to ACTH was found to persist in rats treated with dexamethasone 15 and 3 h before exogenous ACTH (in the presumed absence of a rhythm in endogenous ACTH). Treatment with p-chlorophenylalanine did not affect the daily rise in circulating ACTH levels but did abolish the rhythm in adrenal responsiveness to ACTH. The magnitude of the rhythm in adrenal responsiveness to ACTH is greater than the magnitude of the rhythm in ACTH. Because the rhythms are dissociable, we conclude that in vivo measurements of adrenal corticosteroid levels do not necessarily reflect ACTH levels.", "contents": "Nycthemeral rhythm in adrenal responsiveness to ACTH. Adrenal adenosine 3',5'-cyclic monophosphate (cAMP) and corticosterone responses to exogenous ACTH were found to be about 2.5 times greater in the evening (at lights off) than in the morning (at lights on) in rats. The rhythm in adrenal responsiveness to ACTH was found to persist in rats treated with dexamethasone 15 and 3 h before exogenous ACTH (in the presumed absence of a rhythm in endogenous ACTH). Treatment with p-chlorophenylalanine did not affect the daily rise in circulating ACTH levels but did abolish the rhythm in adrenal responsiveness to ACTH. The magnitude of the rhythm in adrenal responsiveness to ACTH is greater than the magnitude of the rhythm in ACTH. Because the rhythms are dissociable, we conclude that in vivo measurements of adrenal corticosteroid levels do not necessarily reflect ACTH levels."}
{"id": "PMID:215041", "title": "Agonist-induced secretions and potassium release from rat submandibular gland slices.", "content": "Secretory activity induced by stimulation of alpha-adrenergic, beta-adrenergic, and muscarinic cholingeric receptors and by dibutyryl cAMP and 8-bromo cGMP has been investigated in rat submandibular tissue slices. Isoproterenol produced a sialic acid secretion from the acinar cells that was inhibited by propranolol, but not by phenoxybenzamine or atropine. Dibutyryl cAMP produced a sialic acid secretion from the acinar cells that was not inhibited by propranolol, phenoxybenzamine, or atropine. Both norepinephrine and acetylcholine produced significant secretion of sialic acid but at a reduced efficacy. Norepinephrine stimulated both peptide hydrolase secretion from the granular duct cells and a release of K+ from the acinar cells. Both actions were inhibited by phenoxybenzamine, but not by propranolol or atropine. Acetylcholine stimulated a minimal secretion of peptide hydrolase from the granular duct cells and a significant release of K+ from the acinar cells. The norepinephrine- and acetylcholine-stimulated release of K+ was increased after the addition of 1 mM ouabain. High concentrations of 8-bromo cGMP induced a K+ efflux that was not inhibited by phenoxybenzamine or atropine. Vacuolation of the acinar cells was correlated with K+ release.", "contents": "Agonist-induced secretions and potassium release from rat submandibular gland slices. Secretory activity induced by stimulation of alpha-adrenergic, beta-adrenergic, and muscarinic cholingeric receptors and by dibutyryl cAMP and 8-bromo cGMP has been investigated in rat submandibular tissue slices. Isoproterenol produced a sialic acid secretion from the acinar cells that was inhibited by propranolol, but not by phenoxybenzamine or atropine. Dibutyryl cAMP produced a sialic acid secretion from the acinar cells that was not inhibited by propranolol, phenoxybenzamine, or atropine. Both norepinephrine and acetylcholine produced significant secretion of sialic acid but at a reduced efficacy. Norepinephrine stimulated both peptide hydrolase secretion from the granular duct cells and a release of K+ from the acinar cells. Both actions were inhibited by phenoxybenzamine, but not by propranolol or atropine. Acetylcholine stimulated a minimal secretion of peptide hydrolase from the granular duct cells and a significant release of K+ from the acinar cells. The norepinephrine- and acetylcholine-stimulated release of K+ was increased after the addition of 1 mM ouabain. High concentrations of 8-bromo cGMP induced a K+ efflux that was not inhibited by phenoxybenzamine or atropine. Vacuolation of the acinar cells was correlated with K+ release."}
{"id": "PMID:215042", "title": "Action of secretagogues on a new preparation of functionally intact, isolated pancreatic acini.", "content": "Isolated pancreatic acini were prepared by a new method from mouse and rat pancreases by digestion with purified collagenase and chymotrypsin followed by mechanical shearing. Acini were structurally similar to those of the intact pancreas, having a normal luminal structure but with the basal acinar cell membranes exposed to the incubation medium. Amylase release in response to both cholinergic analogues and the cholecystokinin analogues caerulein and pentagastrin was comparable to that of the intact pancreas, but was much greater than previously reported for isolated acinar cells. Cholinergic-stimulated release was inhibited by atropine with a Ki value of 1.4 nM which is comparable to other muscarinic receptors. All agonists tested, when added at supramaximal concentrations, produced a submaximal release of amylase even though ATP levels and the release of slowly exchanging 45Ca2+ were normal or increased. Acini releasing amylase submaximally after being exposed to supramaximal concentrations of carbachol failed to respond to a maximal amount of caerulein or to the Ca2+ ionophore A23187. It is concluded that the decreased response (desensitization) is a postreceptor phenomenon and possibly mediated by Ca2+ itself.", "contents": "Action of secretagogues on a new preparation of functionally intact, isolated pancreatic acini. Isolated pancreatic acini were prepared by a new method from mouse and rat pancreases by digestion with purified collagenase and chymotrypsin followed by mechanical shearing. Acini were structurally similar to those of the intact pancreas, having a normal luminal structure but with the basal acinar cell membranes exposed to the incubation medium. Amylase release in response to both cholinergic analogues and the cholecystokinin analogues caerulein and pentagastrin was comparable to that of the intact pancreas, but was much greater than previously reported for isolated acinar cells. Cholinergic-stimulated release was inhibited by atropine with a Ki value of 1.4 nM which is comparable to other muscarinic receptors. All agonists tested, when added at supramaximal concentrations, produced a submaximal release of amylase even though ATP levels and the release of slowly exchanging 45Ca2+ were normal or increased. Acini releasing amylase submaximally after being exposed to supramaximal concentrations of carbachol failed to respond to a maximal amount of caerulein or to the Ca2+ ionophore A23187. It is concluded that the decreased response (desensitization) is a postreceptor phenomenon and possibly mediated by Ca2+ itself."}
{"id": "PMID:215043", "title": "Inducibility of the hepatic drug-metabolizing capacity of mice infected with Schistosoma mansoni.", "content": "The activities of some hepatic microsomal drug metabolizing enzymes, which are markedly depressed in mice infected with Schistosoma mansoni, can be increased by treatment with phenobarbital or 3-methylcholanthrene. Administration of these compounds to infected mice increased the capacity of the liver to metabolize drugs up to the maximum level inducible in non-infected animals. However, the increased hepatic microsomal mass, reflected in glucose 6-phosphatase activities and cytochrome b5 levels, observed in schistosome-infected mice, was not increased further by the same treatment. The changes in the activities of several drug metabolizing enzymes in vitro were confirmed in vivo by determination of hexobarbital-induced sleeping time and zoxazolamine-induced paralysis duration.", "contents": "Inducibility of the hepatic drug-metabolizing capacity of mice infected with Schistosoma mansoni. The activities of some hepatic microsomal drug metabolizing enzymes, which are markedly depressed in mice infected with Schistosoma mansoni, can be increased by treatment with phenobarbital or 3-methylcholanthrene. Administration of these compounds to infected mice increased the capacity of the liver to metabolize drugs up to the maximum level inducible in non-infected animals. However, the increased hepatic microsomal mass, reflected in glucose 6-phosphatase activities and cytochrome b5 levels, observed in schistosome-infected mice, was not increased further by the same treatment. The changes in the activities of several drug metabolizing enzymes in vitro were confirmed in vivo by determination of hexobarbital-induced sleeping time and zoxazolamine-induced paralysis duration."}
{"id": "PMID:215045", "title": "Serum 5'-nucleotide phosphodiesterase as a predictor of hepatic metastases in gastrointestinal cancer.", "content": "Isoenzyme V of 5'-nucleotide phosphodiesterase (5'-NPD-V) is present in the peripheral sera of patients with hepatic metastases. A total of 122 patients underwent prospective serologic analysis followed by operation for primary tumors of the gastrointestinal tract and careful evaluation of the liver. A positive 5'-NPD-V assay was found in fifty-nine of sixty patients with liver metastases. A negative 5'-NPD-V assay was found in forty-three of sixty-two patients with no evidence of hepatic metastases. The accuracy of the test was 84 per cent, and the predictive value was 75 per cent. Serum 5'-NPD-V was abnormal significantly more frequently in patients with metastatic liver disease than were liver scans or carcinoembryonic antigen (CEA), alpha fetoprotein, serum glutamic oxalacetic transaminase (SGOT), and total serum bilirubin or serum alkaline phosphatase levels.", "contents": "Serum 5'-nucleotide phosphodiesterase as a predictor of hepatic metastases in gastrointestinal cancer. Isoenzyme V of 5'-nucleotide phosphodiesterase (5'-NPD-V) is present in the peripheral sera of patients with hepatic metastases. A total of 122 patients underwent prospective serologic analysis followed by operation for primary tumors of the gastrointestinal tract and careful evaluation of the liver. A positive 5'-NPD-V assay was found in fifty-nine of sixty patients with liver metastases. A negative 5'-NPD-V assay was found in forty-three of sixty-two patients with no evidence of hepatic metastases. The accuracy of the test was 84 per cent, and the predictive value was 75 per cent. Serum 5'-NPD-V was abnormal significantly more frequently in patients with metastatic liver disease than were liver scans or carcinoembryonic antigen (CEA), alpha fetoprotein, serum glutamic oxalacetic transaminase (SGOT), and total serum bilirubin or serum alkaline phosphatase levels."}
{"id": "PMID:215048", "title": "Electron microscopy of retinal tapetum (Caiman crocodilus).", "content": "The distribution and ultrastructure of the retinal tapetum lucidum in Caiman crocodilus is described. In the light adapted eye the tapetum is recognized in the superior half of the fundus. It consists of guanine containing crystalline platelets which are spread almost over the entire retinal pigment epithelial cells which can be divided into different layers: 1. The basal surface facing the choriocapillary vessels is differentiated into numerous densely packed true microfolds which are commonly described as \"basal infoldings\". 2. A remarkable high content of mitochondria as well as a great number of lipid droplet-like spherical bodies is observed. 3. In the nuclear zone a Golgi apparatus and all stages of phagocytosis are found. 4. Within the level of intercellular junctions, crystalline platelets are arranged mainly perpendicularly to the long axis of the neighbouring receptor cells, whereas 5. platelets in large pigment epithelial cell processes extending from the apical cell surface between the photoreceptors are oriented parallel to the receptor axis. 6. Heavy pigmentation of the apical tips of pigment cell processes by melanosomes is observed, but only within the lower half of the fundus. The functional significance of the tapetum of Caiman crocodilus is discussed.", "contents": "Electron microscopy of retinal tapetum (Caiman crocodilus). The distribution and ultrastructure of the retinal tapetum lucidum in Caiman crocodilus is described. In the light adapted eye the tapetum is recognized in the superior half of the fundus. It consists of guanine containing crystalline platelets which are spread almost over the entire retinal pigment epithelial cells which can be divided into different layers: 1. The basal surface facing the choriocapillary vessels is differentiated into numerous densely packed true microfolds which are commonly described as \"basal infoldings\". 2. A remarkable high content of mitochondria as well as a great number of lipid droplet-like spherical bodies is observed. 3. In the nuclear zone a Golgi apparatus and all stages of phagocytosis are found. 4. Within the level of intercellular junctions, crystalline platelets are arranged mainly perpendicularly to the long axis of the neighbouring receptor cells, whereas 5. platelets in large pigment epithelial cell processes extending from the apical cell surface between the photoreceptors are oriented parallel to the receptor axis. 6. Heavy pigmentation of the apical tips of pigment cell processes by melanosomes is observed, but only within the lower half of the fundus. The functional significance of the tapetum of Caiman crocodilus is discussed."}
{"id": "PMID:215049", "title": "Ultrastructural studies of extraocular muscles in ocular motility disorders. II. Morphological analysis of 38 biopsies.", "content": "Thirty eight extraocular muscle biopsies obtained from thirty patients (1 normal and 29 affected with various kinds of ocular motility disorders such as strabismus, Duane's syndrome, paralysis), were studied by electron microscopy. Except for the control biopsy considered as normal, they showed: atrophy, disorganization of myofilaments, double Z-disks, rods, curving arrays of myofibrils, concentrically disposed electron-dense sarcotubules, clusters of mitochondria with numerous modifications of their cristae, and subsarcolemmal inclusions, such as dense bodies, laminated bodies, lipofuscin granules and lipid droplets. In addition, subsarcolemmal granulo-fibrillar aggregates, characterized by periodic granulated foci spaced at about 120 nm intervals, were seen in all the biopsies, even in that of the control case. The authors stress the pecularity of the granulo-fibrillar aggregates which, up to now, have never been described in skeletal muscles and the function of which in the extraocular muscles fibers is impossible to define. They point out the difficulty in determining if the motility disturbances may be related to the various changes observed in extraocular muscles of squinting eyes.", "contents": "Ultrastructural studies of extraocular muscles in ocular motility disorders. II. Morphological analysis of 38 biopsies. Thirty eight extraocular muscle biopsies obtained from thirty patients (1 normal and 29 affected with various kinds of ocular motility disorders such as strabismus, Duane's syndrome, paralysis), were studied by electron microscopy. Except for the control biopsy considered as normal, they showed: atrophy, disorganization of myofilaments, double Z-disks, rods, curving arrays of myofibrils, concentrically disposed electron-dense sarcotubules, clusters of mitochondria with numerous modifications of their cristae, and subsarcolemmal inclusions, such as dense bodies, laminated bodies, lipofuscin granules and lipid droplets. In addition, subsarcolemmal granulo-fibrillar aggregates, characterized by periodic granulated foci spaced at about 120 nm intervals, were seen in all the biopsies, even in that of the control case. The authors stress the pecularity of the granulo-fibrillar aggregates which, up to now, have never been described in skeletal muscles and the function of which in the extraocular muscles fibers is impossible to define. They point out the difficulty in determining if the motility disturbances may be related to the various changes observed in extraocular muscles of squinting eyes."}
{"id": "PMID:215060", "title": "Investigations on the turnover of adrenocortical mitochondria. XII. Studies on the mechanism of the ACTH-induced elongation of the half-life of rat zona fasciculata mitochondria.", "content": "The half-life of rat adrenocortical mitochondria was determined by high resolution autoradiography and liquid scintillation spectroscopy as previously described (Mazzocchi et al., '76). The results obtained by the two approaches were in good agreement. In the normal rats the half-life of adrenocortical mitochondria averaged 11 days. ACTH significantly increased mitochondrial half-life to about 16 days, and chloramphenicol significantly decreased this parameter in both untreated and ACTH-administered rats to about seven days. It is suggested that the ACTH-induced maintenance and slowing down of the degradation rate of adrenocortical mitochondria requires continuous mitochondrial DNA-dependent protein synthesis.", "contents": "Investigations on the turnover of adrenocortical mitochondria. XII. Studies on the mechanism of the ACTH-induced elongation of the half-life of rat zona fasciculata mitochondria. The half-life of rat adrenocortical mitochondria was determined by high resolution autoradiography and liquid scintillation spectroscopy as previously described (Mazzocchi et al., '76). The results obtained by the two approaches were in good agreement. In the normal rats the half-life of adrenocortical mitochondria averaged 11 days. ACTH significantly increased mitochondrial half-life to about 16 days, and chloramphenicol significantly decreased this parameter in both untreated and ACTH-administered rats to about seven days. It is suggested that the ACTH-induced maintenance and slowing down of the degradation rate of adrenocortical mitochondria requires continuous mitochondrial DNA-dependent protein synthesis."}
{"id": "PMID:215061", "title": "Scanning and transmission electron microscopic study of equine infectious anemia virus.", "content": "Scanning and transmission electron microscopy were used to study in detail the morphogenesis and replication of equine infectious anemia virus (EIAV) in cultured, persistently infected equine fetal kidney fibroblasts. The EIAV was shown by thin-section electron microscopy to resemble morphologically more closely the members of the genus Lenti-virus in the family Retroviridae than other genera. Scanning electron microscopy demonstrated budding virus on only about 5% of the equine fetal kidney fibroblasts; however, the entire surface of these cells was involved in viral replication. Except where virus budding was observed, EIAV-infected cells were smooth and free of the topographic surface alterations characteristic of cells transformed by type C retroviruses. The morphologic relationship of EIAV and pathologic manifestations of EIAV infection to those of other Retroviridae are discussed.", "contents": "Scanning and transmission electron microscopic study of equine infectious anemia virus. Scanning and transmission electron microscopy were used to study in detail the morphogenesis and replication of equine infectious anemia virus (EIAV) in cultured, persistently infected equine fetal kidney fibroblasts. The EIAV was shown by thin-section electron microscopy to resemble morphologically more closely the members of the genus Lenti-virus in the family Retroviridae than other genera. Scanning electron microscopy demonstrated budding virus on only about 5% of the equine fetal kidney fibroblasts; however, the entire surface of these cells was involved in viral replication. Except where virus budding was observed, EIAV-infected cells were smooth and free of the topographic surface alterations characteristic of cells transformed by type C retroviruses. The morphologic relationship of EIAV and pathologic manifestations of EIAV infection to those of other Retroviridae are discussed."}
{"id": "PMID:215067", "title": "[EEC syndrome: ectrodactyly, ectodermal dysplasia and cleft lip-palate (author's transl)].", "content": "Authors present a new and complete from of EEC syndrome (ectrodactyly, ectodermal dysplasia and cleft lip-palate), analysing its' clinical, genetic and therapeutic aspects. Syndrome malformations involving mainly mesenchymal tissue and with diverse clinical expression suggest a heterogenetic heredity. Participation of environmental and unknown factors is not excluded.", "contents": "[EEC syndrome: ectrodactyly, ectodermal dysplasia and cleft lip-palate (author's transl)]. Authors present a new and complete from of EEC syndrome (ectrodactyly, ectodermal dysplasia and cleft lip-palate), analysing its' clinical, genetic and therapeutic aspects. Syndrome malformations involving mainly mesenchymal tissue and with diverse clinical expression suggest a heterogenetic heredity. Participation of environmental and unknown factors is not excluded."}
{"id": "PMID:215070", "title": "A correction to the TW2 RUS-based tables for predicting adult height.", "content": "An error in the table for predicting the adult height of girls from RUS bone age, height and age, is identified and corrected.", "contents": "A correction to the TW2 RUS-based tables for predicting adult height. An error in the table for predicting the adult height of girls from RUS bone age, height and age, is identified and corrected."}
{"id": "PMID:215071", "title": "Genetic polymorphism of human phosphoglycolate phosphatase (PGP).", "content": "1. A method has been devised for the detection after starch-gel electrophoresis of phosphoglycolate phosphatase (PGP) isozymes. 2. PGP isozymes can be detected in all human tissues including red cells, lymphocytes and cultured fibroblasts. The highest activities occur in skeletal muscle and cardiac muscle. 3. PGP is a relatively specific phosphatase which shows enhanced activity in the presence of mercaptoethanol at a neutral pH.4. Six different commonly occurring electrophoretic types of PGP have been identified. Family studies indicate that they are determined by three alleles at an autosomal locus (PGP). 5. The gene frequencies of PGP1, PGP2 and PGP3 in a random sample of Europeans were 0.826, 0.129 and 0.045 respectively. 6. The three-banded isozyme patterns seen in heterozygotes suggest that PGP is a dimeric enzyme.", "contents": "Genetic polymorphism of human phosphoglycolate phosphatase (PGP). 1. A method has been devised for the detection after starch-gel electrophoresis of phosphoglycolate phosphatase (PGP) isozymes. 2. PGP isozymes can be detected in all human tissues including red cells, lymphocytes and cultured fibroblasts. The highest activities occur in skeletal muscle and cardiac muscle. 3. PGP is a relatively specific phosphatase which shows enhanced activity in the presence of mercaptoethanol at a neutral pH.4. Six different commonly occurring electrophoretic types of PGP have been identified. Family studies indicate that they are determined by three alleles at an autosomal locus (PGP). 5. The gene frequencies of PGP1, PGP2 and PGP3 in a random sample of Europeans were 0.826, 0.129 and 0.045 respectively. 6. The three-banded isozyme patterns seen in heterozygotes suggest that PGP is a dimeric enzyme."}
{"id": "PMID:215069", "title": "[Ultrastructural localization of the oxydasic activity in Toxoplasma gondii (author's transl)].", "content": "Toxoplasma belonging on the RH strain were studied under a transmission electron microscope. The activities looked for were: peroxidase, cytochrome oxydase and acid phosphatase. An oxydasic cytochrome respiratory activity was seen. It is localised on the crests and on the peripheral membrane of the mitochondria of Toxoplasma gondii. In the given experimental conditions, no such activity appeared in the other intracytoplasmic organels of the parasite, nor in the vacuoles of the host-cells containing living toxoplasma but the organels of those host-cells presented an oxydasic activity.", "contents": "[Ultrastructural localization of the oxydasic activity in Toxoplasma gondii (author's transl)]. Toxoplasma belonging on the RH strain were studied under a transmission electron microscope. The activities looked for were: peroxidase, cytochrome oxydase and acid phosphatase. An oxydasic cytochrome respiratory activity was seen. It is localised on the crests and on the peripheral membrane of the mitochondria of Toxoplasma gondii. In the given experimental conditions, no such activity appeared in the other intracytoplasmic organels of the parasite, nor in the vacuoles of the host-cells containing living toxoplasma but the organels of those host-cells presented an oxydasic activity."}
{"id": "PMID:215068", "title": "Fibrous histiocytoma of the trachea.", "content": "Intratracheal tumors are rare in children. A case is reported of a two-year-old female child with a fibrous histiocytoma of the trachea which caused severe respiratory obstruction and persistent right middle lobe pneumonia. Fibrous histiocytomas are basically benign tumors of histiocytes and have been mistaken for other tumors such as fibroma, sclerosing hemangioma, neurilemoma, fibromatosis, hemangiopericytoma, fibrosarcoma, and some primitive sarcomas. Fibrous histiocytomas have not been reported in the trachea or bronchi. The patient was treated with endoscopic removal of the tumor, and has remained free of disease to this date.", "contents": "Fibrous histiocytoma of the trachea. Intratracheal tumors are rare in children. A case is reported of a two-year-old female child with a fibrous histiocytoma of the trachea which caused severe respiratory obstruction and persistent right middle lobe pneumonia. Fibrous histiocytomas are basically benign tumors of histiocytes and have been mistaken for other tumors such as fibroma, sclerosing hemangioma, neurilemoma, fibromatosis, hemangiopericytoma, fibrosarcoma, and some primitive sarcomas. Fibrous histiocytomas have not been reported in the trachea or bronchi. The patient was treated with endoscopic removal of the tumor, and has remained free of disease to this date."}
{"id": "PMID:215072", "title": "The syndrome of diabetic amyotrophy.", "content": "Changes in the electromyograms and motor nerve conduction velocities in 12 patients with diabetic amyotrophy suggested mild distal and moderate proximal neuropathy in the lower limbs. Histological and histochemical findings in the vastus medialis muscles were consistent with denervation. Electron microscopical examination of the vastus medialis muscles in 6 patients revealed myofibrillar degeneration. One patient had abnormal mitochondria and tubular aggregates. The basement membranes of the intramuscular capillaries were thickened in all but 1 patient. Histochemical staining of the myoneural junctions showed changes consistent with degeneration and regeneration. We conclude that diabetic amyotrophy is a distinct clinical entity and is secondary to metabolic derangement rather than  diabetic microangiopathy.", "contents": "The syndrome of diabetic amyotrophy. Changes in the electromyograms and motor nerve conduction velocities in 12 patients with diabetic amyotrophy suggested mild distal and moderate proximal neuropathy in the lower limbs. Histological and histochemical findings in the vastus medialis muscles were consistent with denervation. Electron microscopical examination of the vastus medialis muscles in 6 patients revealed myofibrillar degeneration. One patient had abnormal mitochondria and tubular aggregates. The basement membranes of the intramuscular capillaries were thickened in all but 1 patient. Histochemical staining of the myoneural junctions showed changes consistent with degeneration and regeneration. We conclude that diabetic amyotrophy is a distinct clinical entity and is secondary to metabolic derangement rather than  diabetic microangiopathy."}
{"id": "PMID:215074", "title": "Glucocorticoid effects on the edrophonium responsiveness of normal and degenerating mammalian motor nerve terminals.", "content": "An intensive short-term triamcinolone regimen in cats preserves the prejunctional actions of edrophonium in degenerating motor nerves. These edrophonium actions include the induction of a stimulus-dependent afterdischarge and the initiation of fasciculations. The relationship between fasciculations and stimulus-dependent afterdischarge is discussed. The glucocorticoid preservation of these edrophonium effects is like that previously reported for the preservation of posttetanic facilitation in motor nerves equally compromised. The results therefore show that glucocorticoid and facilitatory drug actions synergize to increase facilitation in degenerating but still functional motor nerves. This drug synergy is comparable to that which occurs in normal motor nerves. This interaction may provide a basis for effectively combining glucocorticoid and facilitatory drugs in the treatment of myasthenia gravis.", "contents": "Glucocorticoid effects on the edrophonium responsiveness of normal and degenerating mammalian motor nerve terminals. An intensive short-term triamcinolone regimen in cats preserves the prejunctional actions of edrophonium in degenerating motor nerves. These edrophonium actions include the induction of a stimulus-dependent afterdischarge and the initiation of fasciculations. The relationship between fasciculations and stimulus-dependent afterdischarge is discussed. The glucocorticoid preservation of these edrophonium effects is like that previously reported for the preservation of posttetanic facilitation in motor nerves equally compromised. The results therefore show that glucocorticoid and facilitatory drug actions synergize to increase facilitation in degenerating but still functional motor nerves. This drug synergy is comparable to that which occurs in normal motor nerves. This interaction may provide a basis for effectively combining glucocorticoid and facilitatory drugs in the treatment of myasthenia gravis."}
{"id": "PMID:215077", "title": "Attenuated dynamic responses of primary endings of muscle spindles: a basis for depressed tendon responses in acrylamide neuropathy.", "content": "Depressed or lost tendon reflexes commonly observed in patients with peripheral neuropathies may result partly from attenuation of the dynamic discharge from the primary endings of muscle spindles. This possibility was investigated in cats with an experimental neuropathy induced with acrylamide (30 mg/kg/day intramuscularly). Achilles tendon reflexes and the dynamic discharge from primary muscle spindles were evaluated after five or ten injections of acrylamide. After five injections the animals were moderately impaired neurologically, the Achilles tendon reflex was difficult to elicit in 2 of 5 animals, and the dynamic responses of primary endings of soleus muscle spindles to stretch were depressed. Following ten injections of acrylamide the cats were severely impaired neurologically; tendon responses were either absent or difficult to elicit, and the dynamic responses of their muscle spindles to stretch were reduced by 50% (p less than 0.01). Additionally, the spindels responded to stretch with only 20 to 30% the normal number of afferent impulses. These data suggest that lost tendon responses in acrylamide neuropathy result in part from inadequate activation of motoneurons by spindle afferent discharge.", "contents": "Attenuated dynamic responses of primary endings of muscle spindles: a basis for depressed tendon responses in acrylamide neuropathy. Depressed or lost tendon reflexes commonly observed in patients with peripheral neuropathies may result partly from attenuation of the dynamic discharge from the primary endings of muscle spindles. This possibility was investigated in cats with an experimental neuropathy induced with acrylamide (30 mg/kg/day intramuscularly). Achilles tendon reflexes and the dynamic discharge from primary muscle spindles were evaluated after five or ten injections of acrylamide. After five injections the animals were moderately impaired neurologically, the Achilles tendon reflex was difficult to elicit in 2 of 5 animals, and the dynamic responses of primary endings of soleus muscle spindles to stretch were depressed. Following ten injections of acrylamide the cats were severely impaired neurologically; tendon responses were either absent or difficult to elicit, and the dynamic responses of their muscle spindles to stretch were reduced by 50% (p less than 0.01). Additionally, the spindels responded to stretch with only 20 to 30% the normal number of afferent impulses. These data suggest that lost tendon responses in acrylamide neuropathy result in part from inadequate activation of motoneurons by spindle afferent discharge."}
{"id": "PMID:215080", "title": "Evaluation of virucidal compounds for inactivation of rhinovirus on hands.", "content": "Antimicrobial liquids and foams were applied to the hands to determine their virucidal activity against rhinoviruses. Dilute solutions (1%) of iodine in ethyl alcohol or in water were most effective in causing inactivation of rhinovirus when applied immediately after viral contamination. Iodine also had a residual virucidal activity which persisted on the hands for up to 1 h. Less effective inactivation of rhinovirus was observed with foams containing 0.23% hexachlorophene and 58% ethyl alcohol and another containing 0.2% benzalkonium chloride and 50% ethyl alcohol. Ethyl alcohol alone or in a mixture with benzyl alcohol was the least effective preparation tested.", "contents": "Evaluation of virucidal compounds for inactivation of rhinovirus on hands. Antimicrobial liquids and foams were applied to the hands to determine their virucidal activity against rhinoviruses. Dilute solutions (1%) of iodine in ethyl alcohol or in water were most effective in causing inactivation of rhinovirus when applied immediately after viral contamination. Iodine also had a residual virucidal activity which persisted on the hands for up to 1 h. Less effective inactivation of rhinovirus was observed with foams containing 0.23% hexachlorophene and 58% ethyl alcohol and another containing 0.2% benzalkonium chloride and 50% ethyl alcohol. Ethyl alcohol alone or in a mixture with benzyl alcohol was the least effective preparation tested."}
{"id": "PMID:215081", "title": "Effect of treatment with 5-ethyl-2'-deoxyuridine on herpes simplex virus encephalitis in normal and immunosuppressed mice.", "content": "5-Ethyl-2'-deoxyuridine (5-ethyl-dUrd), an analog of thymidine, was evaluated for its capacity to inhibit herpes simplex virus (HSV) replication in vitro and in vivo. The 50% effective dose concentration of 5-ethyl-dUrd for HSV types 1 and 2 (HSV-1 and -2) cultured in Vero cells was 6 and 9 mug/ml, respectively. Levels of 5-ethyl-dUrd 14-fold in excess of the 50% effective dose for HSV-1 did not inhibit the formation of confluent monolayers by Vero cells, suggesting that the compound was not cytotoxic or inhibitory for mammalian cells. In vivo studies showed that 5-ethyl-dUrd was effective in significantly reducing mortality when administered to young adult mice after subcutaneous infection with HSV-2. Intraperitoneal and intravenous inoculation of drug (250 mg/kg per day) resulted in a 50% survivor rate at 15 days. Comparative studies with adenine arabinoside at 250 mg/kg per day gave a 40% survivor rate. Intramuscular injection of 5-ethyl-dUrd at a concentration as high as 2,000 mg/kg per day for 10 days was well tolerated by uninfected animals, and HSV-2-infected mice treated at this dosage had a 100% survival rate. Treatment with 5-ethyl-dUrd at a concentration of 500 mg/kg per day significantly increased the mean survival times of HSV-1- and HSV-2-infected mice immunosuppressed by irradiation; however, the fatal course of the infection was not altered. Assay for virus in tissues showed that 5-ethyl-dUrd treatment delayed progression of the infection into the central nervous system, indicating suppression of virus replication in the tissues.", "contents": "Effect of treatment with 5-ethyl-2'-deoxyuridine on herpes simplex virus encephalitis in normal and immunosuppressed mice. 5-Ethyl-2'-deoxyuridine (5-ethyl-dUrd), an analog of thymidine, was evaluated for its capacity to inhibit herpes simplex virus (HSV) replication in vitro and in vivo. The 50% effective dose concentration of 5-ethyl-dUrd for HSV types 1 and 2 (HSV-1 and -2) cultured in Vero cells was 6 and 9 mug/ml, respectively. Levels of 5-ethyl-dUrd 14-fold in excess of the 50% effective dose for HSV-1 did not inhibit the formation of confluent monolayers by Vero cells, suggesting that the compound was not cytotoxic or inhibitory for mammalian cells. In vivo studies showed that 5-ethyl-dUrd was effective in significantly reducing mortality when administered to young adult mice after subcutaneous infection with HSV-2. Intraperitoneal and intravenous inoculation of drug (250 mg/kg per day) resulted in a 50% survivor rate at 15 days. Comparative studies with adenine arabinoside at 250 mg/kg per day gave a 40% survivor rate. Intramuscular injection of 5-ethyl-dUrd at a concentration as high as 2,000 mg/kg per day for 10 days was well tolerated by uninfected animals, and HSV-2-infected mice treated at this dosage had a 100% survival rate. Treatment with 5-ethyl-dUrd at a concentration of 500 mg/kg per day significantly increased the mean survival times of HSV-1- and HSV-2-infected mice immunosuppressed by irradiation; however, the fatal course of the infection was not altered. Assay for virus in tissues showed that 5-ethyl-dUrd treatment delayed progression of the infection into the central nervous system, indicating suppression of virus replication in the tissues."}
{"id": "PMID:215082", "title": "Characterization of a bacteriocinogenic plasmid in Clostridium perfringens CW55.", "content": "A bacteriocinogenic strain of Clostridium perfringens was exposed to various curing agents known to accelerate the elimination of extrachromosomal DNA, and 20 independently derived mutants that had lost both the ability to produce bacteriocin and their immunity to it were isolated and characterized. All of the mutants were missing at least two specific plasmid bands seen in the agarose gel plasmid profile of the parent strain. Evidence that the two missing bands represented the open circular and closed circular forms of the same plasmid was obtained by X-ray nicking and restriction endonuclease digestion. The data indicated that bacteriocin production and immunity are controlled by a single plasmid, pCW4, with a molecular weight of 5.6 x 10(6) in this strain. Attempts to transfer the bacteriocinogenic plasmid were unsuccessful.", "contents": "Characterization of a bacteriocinogenic plasmid in Clostridium perfringens CW55. A bacteriocinogenic strain of Clostridium perfringens was exposed to various curing agents known to accelerate the elimination of extrachromosomal DNA, and 20 independently derived mutants that had lost both the ability to produce bacteriocin and their immunity to it were isolated and characterized. All of the mutants were missing at least two specific plasmid bands seen in the agarose gel plasmid profile of the parent strain. Evidence that the two missing bands represented the open circular and closed circular forms of the same plasmid was obtained by X-ray nicking and restriction endonuclease digestion. The data indicated that bacteriocin production and immunity are controlled by a single plasmid, pCW4, with a molecular weight of 5.6 x 10(6) in this strain. Attempts to transfer the bacteriocinogenic plasmid were unsuccessful."}
{"id": "PMID:215083", "title": "Contribution of trigeminal and facial reflexes to the localization of Vth, VIIth, and VIIIth cranial nerve dysfunction.", "content": "After a review of electrophysiological studies in 1,500 cases concerning different types of lesions of the trigeminal nerve, the acousticofacial complex, and the brain stem, one can conclude that beside the intensive clinical examination which most often allows a precise topographic diagnosis, study of trigeminofacial and facial reflexes appears to be an essential diagnostic method to determine the topography of the lesions. On the other hand, this study can sometimes contribute to the prognostic evaluation as well as the choice of the approach in some lesions concerning the acousticofacial complex.", "contents": "Contribution of trigeminal and facial reflexes to the localization of Vth, VIIth, and VIIIth cranial nerve dysfunction. After a review of electrophysiological studies in 1,500 cases concerning different types of lesions of the trigeminal nerve, the acousticofacial complex, and the brain stem, one can conclude that beside the intensive clinical examination which most often allows a precise topographic diagnosis, study of trigeminofacial and facial reflexes appears to be an essential diagnostic method to determine the topography of the lesions. On the other hand, this study can sometimes contribute to the prognostic evaluation as well as the choice of the approach in some lesions concerning the acousticofacial complex."}
{"id": "PMID:215084", "title": "Sensitization of Clostridium perfringens spores to heat by gamma radiation.", "content": "Spores of Clostridium perfringens, type A, were given separate or sequential treatments of gamma radiation (0 to 0.7 Mrad) and/or high temperature (93 to 103 degrees C). Prior heating, sufficient to inactivate 40 to 99% of the viable spores, had no effect on the subsequent radiation inactivation rate. Prior irradiation had a sensitizing effect on subsequently heated spores. The degree of sensitization to heat, as measured by thermal inactivation rate, increased with increased radiation pretreatment dose.", "contents": "Sensitization of Clostridium perfringens spores to heat by gamma radiation. Spores of Clostridium perfringens, type A, were given separate or sequential treatments of gamma radiation (0 to 0.7 Mrad) and/or high temperature (93 to 103 degrees C). Prior heating, sufficient to inactivate 40 to 99% of the viable spores, had no effect on the subsequent radiation inactivation rate. Prior irradiation had a sensitizing effect on subsequently heated spores. The degree of sensitization to heat, as measured by thermal inactivation rate, increased with increased radiation pretreatment dose."}
{"id": "PMID:215085", "title": "Viral pollution of surface waters due to chlorinated primary effluents.", "content": "The role of chlorinated primary effluents in viral pollution of the Ottawa River (Ontario) was assessed by examining 282 field samples of wastewaters from two different sewage treatment plants over a 2-year period. The talc-Celite technique was used for sample concentration, and BS-C-1 cells were employed for virus detection. Viruses were detected in 80% (75/94) of raw sewage, 72% (68/94) of primary effluent, and 56% (53/94) of chlorinated effluent samples. Both raw sewage and primary effluent samples contained about 100 viral infective units (VIU) per 100 ml. Chlorination produced a 10- to 50-fold reduction in VIU and gave nearly 2.7 VIU/100 ml of chlorinated primary effluent. With a combined daily chlorinated primary effluent output of approximately 3.7 x 10(8) liters, these two plants were discharging 1.0 x 10(10) VIU per day. Because the river has a mean annual flow of 8.0 x 10(10) liters per day, these two sources alone produced a virus loading of 1.0 VIU/8 liters of the river water. This river also receives at least 9.0 x 10(7) liters of raw sewage per day and undetermined but substantial amounts of storm waters and agricultural wastes. It is used for recreation and acts as a source of potable water for some 6.0 x 10(5) people. In view of the potential of water for disease transmission, discharge of such wastes into the water environment needs to be minimized.", "contents": "Viral pollution of surface waters due to chlorinated primary effluents. The role of chlorinated primary effluents in viral pollution of the Ottawa River (Ontario) was assessed by examining 282 field samples of wastewaters from two different sewage treatment plants over a 2-year period. The talc-Celite technique was used for sample concentration, and BS-C-1 cells were employed for virus detection. Viruses were detected in 80% (75/94) of raw sewage, 72% (68/94) of primary effluent, and 56% (53/94) of chlorinated effluent samples. Both raw sewage and primary effluent samples contained about 100 viral infective units (VIU) per 100 ml. Chlorination produced a 10- to 50-fold reduction in VIU and gave nearly 2.7 VIU/100 ml of chlorinated primary effluent. With a combined daily chlorinated primary effluent output of approximately 3.7 x 10(8) liters, these two plants were discharging 1.0 x 10(10) VIU per day. Because the river has a mean annual flow of 8.0 x 10(10) liters per day, these two sources alone produced a virus loading of 1.0 VIU/8 liters of the river water. This river also receives at least 9.0 x 10(7) liters of raw sewage per day and undetermined but substantial amounts of storm waters and agricultural wastes. It is used for recreation and acts as a source of potable water for some 6.0 x 10(5) people. In view of the potential of water for disease transmission, discharge of such wastes into the water environment needs to be minimized."}
{"id": "PMID:215086", "title": "Potential sources of error during virus thermal inactivation.", "content": "A review of virus thermal inactivation data published in the literature demonstrated variations in reported virus resistance. Examination of the methods used indicated that numerous studies were made by heat processing virus suspensions in test tubes. Duplication of some of the methods using milk suspensions of poliovirus 1 showed virus persistence after heating as a result of uneven temperature distribution inside the test tubes. Unless the containers (preferably sealed ampoules or capillary tubes) are completely submerged in the water bath and agitated vigorously, apparent virus persistence may be encountered.", "contents": "Potential sources of error during virus thermal inactivation. A review of virus thermal inactivation data published in the literature demonstrated variations in reported virus resistance. Examination of the methods used indicated that numerous studies were made by heat processing virus suspensions in test tubes. Duplication of some of the methods using milk suspensions of poliovirus 1 showed virus persistence after heating as a result of uneven temperature distribution inside the test tubes. Unless the containers (preferably sealed ampoules or capillary tubes) are completely submerged in the water bath and agitated vigorously, apparent virus persistence may be encountered."}
{"id": "PMID:215087", "title": "Comparative sensitivity of various cell culture systems for isolation of viruses from wastewater and fecal samples.", "content": "In efforts to define the most sensitive cell culture systems for recovery of viruses from wastewaters, 181 samples were inoculated in parallel into tube cultures of various cell types and were plaqued in bottle and petri dish cultures of three types of monkey kidney cells. Polioviruses were recovered most frequently in the RD line of human rhabdomyosarcoma cells, group A coxsackieviruses in RD and human fetal diploid kidney (HFDK) cells, group B coxsackieviruses in the BGM line of African green monkey kidney cells, echoviruses in RD and primary rhesus monkey kidney (RhMK) cells, and reoviruses in RhMK cells. BGM cells were unsatisfactory for recovery of viruses other than polioviruses and group B coxsackieviruses, and a line of fetal rhesus monkey kidney (MFK) was not a satisfactory substitute for primary RhMK. With RhMK cells, comparable numbers of virus isolations were made in tube cultures and in plaque assays conducted in bottle cultures, but with BGM and MFK cells, fewer isolations were made by plaquing than by inoculation of tube cultures. In comparative plaque assays on fecal samples under three different overlays in bottle and plate cultures of RhMK, BGM, and MFK cells, it was found that plaquing in the most sensitive system, RhMK, was less efficient for virus recovery than was inoculation of tube cultures of RhMK or HFDK cells. Overall, plaque assays performed in petri dishes in a CO(2) incubator yielded fewer virus isolates than did parallel plaque assays performed in closed bottle cultures. Other limitations of plaque assays for recovery of human enteric viruses are discussed.", "contents": "Comparative sensitivity of various cell culture systems for isolation of viruses from wastewater and fecal samples. In efforts to define the most sensitive cell culture systems for recovery of viruses from wastewaters, 181 samples were inoculated in parallel into tube cultures of various cell types and were plaqued in bottle and petri dish cultures of three types of monkey kidney cells. Polioviruses were recovered most frequently in the RD line of human rhabdomyosarcoma cells, group A coxsackieviruses in RD and human fetal diploid kidney (HFDK) cells, group B coxsackieviruses in the BGM line of African green monkey kidney cells, echoviruses in RD and primary rhesus monkey kidney (RhMK) cells, and reoviruses in RhMK cells. BGM cells were unsatisfactory for recovery of viruses other than polioviruses and group B coxsackieviruses, and a line of fetal rhesus monkey kidney (MFK) was not a satisfactory substitute for primary RhMK. With RhMK cells, comparable numbers of virus isolations were made in tube cultures and in plaque assays conducted in bottle cultures, but with BGM and MFK cells, fewer isolations were made by plaquing than by inoculation of tube cultures. In comparative plaque assays on fecal samples under three different overlays in bottle and plate cultures of RhMK, BGM, and MFK cells, it was found that plaquing in the most sensitive system, RhMK, was less efficient for virus recovery than was inoculation of tube cultures of RhMK or HFDK cells. Overall, plaque assays performed in petri dishes in a CO(2) incubator yielded fewer virus isolates than did parallel plaque assays performed in closed bottle cultures. Other limitations of plaque assays for recovery of human enteric viruses are discussed."}
{"id": "PMID:215088", "title": "Effects of an artificial diet on growth of patients with cystic fibrosis.", "content": "The effects of an artificial diet on growth were examined in a controlled trial on 43 patients with cystic fibrosis. 28 patients received the diet for 12 months. Comparison was made between their growth before, during, and after dietary treatment. Growth changes were also assessed in 15 other patients who received a conventional diet. Artificial dietary treatment led to some improvement in height, weight, subscapular skinfold thickness, and a disproportionate advance of bone age for the group as a whole. Only 10 (36%) patients had a 'clinically' significant improvement in height, weight, or both--i.e. more than 0.5 standard deviation score. Greatest improvements were in young and mildly affected patients. It is proposed that the future use of such an unpleasant and expensive diet should be restricted to a few selected cases, rather than given as routine treatment.", "contents": "Effects of an artificial diet on growth of patients with cystic fibrosis. The effects of an artificial diet on growth were examined in a controlled trial on 43 patients with cystic fibrosis. 28 patients received the diet for 12 months. Comparison was made between their growth before, during, and after dietary treatment. Growth changes were also assessed in 15 other patients who received a conventional diet. Artificial dietary treatment led to some improvement in height, weight, subscapular skinfold thickness, and a disproportionate advance of bone age for the group as a whole. Only 10 (36%) patients had a 'clinically' significant improvement in height, weight, or both--i.e. more than 0.5 standard deviation score. Greatest improvements were in young and mildly affected patients. It is proposed that the future use of such an unpleasant and expensive diet should be restricted to a few selected cases, rather than given as routine treatment."}
{"id": "PMID:215089", "title": "Slow growth of an untreated Wilms's tumour in the adolescent.", "content": "Retrospective radiological documentation of a growing Wilms's tumour in rare. Considered to be a relatively rapidly growing tumour, we present a case where there was adequate radiological evidence of a Wilms's tumour 4 years before the clinical metastatic presentation.", "contents": "Slow growth of an untreated Wilms's tumour in the adolescent. Retrospective radiological documentation of a growing Wilms's tumour in rare. Considered to be a relatively rapidly growing tumour, we present a case where there was adequate radiological evidence of a Wilms's tumour 4 years before the clinical metastatic presentation."}
{"id": "PMID:215090", "title": "Congenital nephrogenic diabetes insipidus in a baby girl.", "content": "A 6-week-old girl with fever, hypernatraemia, dehydration, and polyuria failed to concentrate urine in response to exogenous vasopressin administration. There was no family history of nephrogenic diabetes insipidus. When she was 15 months old, the infusion of vasopressin did not produce an increase in urinary cyclic-AMP.", "contents": "Congenital nephrogenic diabetes insipidus in a baby girl. A 6-week-old girl with fever, hypernatraemia, dehydration, and polyuria failed to concentrate urine in response to exogenous vasopressin administration. There was no family history of nephrogenic diabetes insipidus. When she was 15 months old, the infusion of vasopressin did not produce an increase in urinary cyclic-AMP."}
{"id": "PMID:215091", "title": "Acute toxicity of hydrogen cyanide to freshwater fishes.", "content": "Acute toxicity of hydrogen cyanide was determined at various temperatures from 4 degrees to 30 degrees C and oxygen concentrations of 3.36 to 9.26 mg/L on different life history stages of five species of fish: fathead minnow, Pimephales promelas Refinesque; bluegill, Lepomis macrochirus Rafinesque; yellow perch, Perca flavescens (Mitchill); brook trout, Salvelinus fontinalis (Mitchill); and rainbow trout, Salmo gairdneri Richardson. Median lethal threshold concentrations and 96-hr LC50's were established by flow-through type biassays. Acute toxicity varied from 57 microgram/L for juvenile rainbow trout to 191 microgram/L for field stocks of juvenile fathead minnows. Juvenile fish were more sensitive at lower temperatures and at oxygen levels below 5 mg/L. For most species juveniles were most sensitive and eggs more resistant.", "contents": "Acute toxicity of hydrogen cyanide to freshwater fishes. Acute toxicity of hydrogen cyanide was determined at various temperatures from 4 degrees to 30 degrees C and oxygen concentrations of 3.36 to 9.26 mg/L on different life history stages of five species of fish: fathead minnow, Pimephales promelas Refinesque; bluegill, Lepomis macrochirus Rafinesque; yellow perch, Perca flavescens (Mitchill); brook trout, Salvelinus fontinalis (Mitchill); and rainbow trout, Salmo gairdneri Richardson. Median lethal threshold concentrations and 96-hr LC50's were established by flow-through type biassays. Acute toxicity varied from 57 microgram/L for juvenile rainbow trout to 191 microgram/L for field stocks of juvenile fathead minnows. Juvenile fish were more sensitive at lower temperatures and at oxygen levels below 5 mg/L. For most species juveniles were most sensitive and eggs more resistant."}
{"id": "PMID:215092", "title": "Localization  of occult insulin secreting tumors of the pancreas.", "content": "Percutaneous transhepatic portal venography (PTP) and selective portal blood sample collection for immunoreactive insulin (IRI) analyses was done in four patients who had clinical evidence of the presence of an insulin secreting tumor, but selective arteriogrphy of the pancreas did not visualize any insulinomas. In all patients the clinical diagnosis was confirmed and the localization of the tumors could be calculated with the aid of the PTP and the IRI values detected in different parts of the portal trees. Because no tumor was found at the operation in two patients, despite careful exploration of the pancreas, blind distal pancreatectomy was performed to the point suggested with the help of the investigations, and insulinomas were found close to the resection lines. In the two other patients the proposed localization of the tumor preoperatively was confirmed. There have been no postoperative hypoglycemic symptoms.", "contents": "Localization  of occult insulin secreting tumors of the pancreas. Percutaneous transhepatic portal venography (PTP) and selective portal blood sample collection for immunoreactive insulin (IRI) analyses was done in four patients who had clinical evidence of the presence of an insulin secreting tumor, but selective arteriogrphy of the pancreas did not visualize any insulinomas. In all patients the clinical diagnosis was confirmed and the localization of the tumors could be calculated with the aid of the PTP and the IRI values detected in different parts of the portal trees. Because no tumor was found at the operation in two patients, despite careful exploration of the pancreas, blind distal pancreatectomy was performed to the point suggested with the help of the investigations, and insulinomas were found close to the resection lines. In the two other patients the proposed localization of the tumor preoperatively was confirmed. There have been no postoperative hypoglycemic symptoms."}
{"id": "PMID:215093", "title": "Microanalytical RPC-5 columns for rapid chromatography of aminoacyl-tRNAs.", "content": "A microanalytical reversed-phase chromatographic system for the separation of aminoacyl-tRNA's on microbore (0.3cm X 25cm) columns is described. Chromatography of lysyl-tRNA from polyoma virus transformed mouse fibroblasts revealed at least seven identifiable isoacceptors. The system has the advantages of speed, sensitivity and excellent resolution of isoaccepting tRNA's.", "contents": "Microanalytical RPC-5 columns for rapid chromatography of aminoacyl-tRNAs. A microanalytical reversed-phase chromatographic system for the separation of aminoacyl-tRNA's on microbore (0.3cm X 25cm) columns is described. Chromatography of lysyl-tRNA from polyoma virus transformed mouse fibroblasts revealed at least seven identifiable isoacceptors. The system has the advantages of speed, sensitivity and excellent resolution of isoaccepting tRNA's."}
{"id": "PMID:215094", "title": "A novel method for the isolation and study of a magnetotactic bacterium.", "content": "The magnetococcus, a magnetotactic bacterium, has been grown in a complex simulated natural environment. Sufficiently pure samples of cells were obtained magnetically making axenic cultures unnecessary for many purposes. The magnetococcus is a Gram-negative coccus, 1.6 micron in diameter and readily distinguished by highly refractile inclusions and its magnetotactic behavior. This organism is actively motile by means of two bundles of flagella. Electron dense ferromagnetic inclusions were localized between the flagellar bundles. Collections of magnetococci were morphologically homogeneous and negligibly contaminated by extraneous bacteria. DNA extracted from pooled collections of cells was homogeneous by analytical CsC1 centrifugation. The guanine-cytosine content was 61.7%. Total iron by percent cellular dry weight was 3.8%. Comparisons with a previously described magnetotactic marine coccus were made.", "contents": "A novel method for the isolation and study of a magnetotactic bacterium. The magnetococcus, a magnetotactic bacterium, has been grown in a complex simulated natural environment. Sufficiently pure samples of cells were obtained magnetically making axenic cultures unnecessary for many purposes. The magnetococcus is a Gram-negative coccus, 1.6 micron in diameter and readily distinguished by highly refractile inclusions and its magnetotactic behavior. This organism is actively motile by means of two bundles of flagella. Electron dense ferromagnetic inclusions were localized between the flagellar bundles. Collections of magnetococci were morphologically homogeneous and negligibly contaminated by extraneous bacteria. DNA extracted from pooled collections of cells was homogeneous by analytical CsC1 centrifugation. The guanine-cytosine content was 61.7%. Total iron by percent cellular dry weight was 3.8%. Comparisons with a previously described magnetotactic marine coccus were made."}
{"id": "PMID:215095", "title": "Are prophylactic antiparkinson drugs necessary? A controlled study of procyclidine withdrawal.", "content": "Of 55 aftercare patients receiving long-term treatment with antipsychotic and antiparkinson (AP) drugs, 37 were switched to being given placebo, and 18 remained on a regimen of procyclidine hydrochloride. The dose of antipsychotic was kept constant. After three weeks extrapyramidal side effects (EPS) developed in 54% of those patients receiving placebo and in none of those receiving procyclidine (P less than .002): Twenty-seven percent of the placebo group had EPS without akinesia, and in the same percentage akinesia developed (P = .003). We believe the risk-benefit ratio favors the routine use of AP drugs for prophylaxis and maintenance so as to avoid misdiagnosing as psychopathology, unspontaneity due to akinesia, and to reduce unreliable pill-taking due to EPS.", "contents": "Are prophylactic antiparkinson drugs necessary? A controlled study of procyclidine withdrawal. Of 55 aftercare patients receiving long-term treatment with antipsychotic and antiparkinson (AP) drugs, 37 were switched to being given placebo, and 18 remained on a regimen of procyclidine hydrochloride. The dose of antipsychotic was kept constant. After three weeks extrapyramidal side effects (EPS) developed in 54% of those patients receiving placebo and in none of those receiving procyclidine (P less than .002): Twenty-seven percent of the placebo group had EPS without akinesia, and in the same percentage akinesia developed (P = .003). We believe the risk-benefit ratio favors the routine use of AP drugs for prophylaxis and maintenance so as to avoid misdiagnosing as psychopathology, unspontaneity due to akinesia, and to reduce unreliable pill-taking due to EPS."}
{"id": "PMID:215096", "title": "Human pharmacology and abuse potential of the analgesic buprenorphine: a potential agent for treating narcotic addiction.", "content": "Buprenorphine was evaluated for its abuse potential and utility in treating narcotic addiction. The drug was morphine-like but was 25 to 50 times more potent than morphine and was longer-acting. Little if any physical dependence of clinical significance was produced by buprenorphine. The effects of morphine to 120-mg doses were blocked by buprenorphine, a blockade that persisted for 29 1/2 hours. In man, buprenorphine has less intrinsic activity than morphine, and as such, as a low abuse potential. Moreover, the drug has potential for treating narcotic addiction since it is acceptable to addicts, is long-acting, produces a low level of physical dependence such that patients may be easily detoxified, is less toxic than drugs used for maintenance therapy, and blocks the effects of narcotics.", "contents": "Human pharmacology and abuse potential of the analgesic buprenorphine: a potential agent for treating narcotic addiction. Buprenorphine was evaluated for its abuse potential and utility in treating narcotic addiction. The drug was morphine-like but was 25 to 50 times more potent than morphine and was longer-acting. Little if any physical dependence of clinical significance was produced by buprenorphine. The effects of morphine to 120-mg doses were blocked by buprenorphine, a blockade that persisted for 29 1/2 hours. In man, buprenorphine has less intrinsic activity than morphine, and as such, as a low abuse potential. Moreover, the drug has potential for treating narcotic addiction since it is acceptable to addicts, is long-acting, produces a low level of physical dependence such that patients may be easily detoxified, is less toxic than drugs used for maintenance therapy, and blocks the effects of narcotics."}
{"id": "PMID:215097", "title": "Effects of a dopamine agonist piribedil in depressed patients: relationship of pretreatment homovanillic acid to antidepressant response.", "content": "Piribedil, a compound that stimulates dopamine receptors in a relatively specific fashion, was administered to 11 hospitalized depressed patients. The dopamine agonist significantly decreased rapid eye movement (REM) sleep and percent REM sleep and increased REM latency. Piribedil decreased the probenecid-induced accumulation of the dopamine metabolite homovanillic acid (HVA) in CSF. A range of mild to moderate antidepressant effects was noted; one patient worsened and one developed recurrent manic episodes. The degree of improvement in depression was negatively correlated with pretreatment values of HVA in CSF (r = -.66, P less than .05). These data suggest that the heterogeneity of clinical response may be related to biological differences in depressed patients and that those with low initial dopaminergic function respond best to increased dopamine receptor stimulation.", "contents": "Effects of a dopamine agonist piribedil in depressed patients: relationship of pretreatment homovanillic acid to antidepressant response. Piribedil, a compound that stimulates dopamine receptors in a relatively specific fashion, was administered to 11 hospitalized depressed patients. The dopamine agonist significantly decreased rapid eye movement (REM) sleep and percent REM sleep and increased REM latency. Piribedil decreased the probenecid-induced accumulation of the dopamine metabolite homovanillic acid (HVA) in CSF. A range of mild to moderate antidepressant effects was noted; one patient worsened and one developed recurrent manic episodes. The degree of improvement in depression was negatively correlated with pretreatment values of HVA in CSF (r = -.66, P less than .05). These data suggest that the heterogeneity of clinical response may be related to biological differences in depressed patients and that those with low initial dopaminergic function respond best to increased dopamine receptor stimulation."}
{"id": "PMID:215098", "title": "[Some physical properties of the virus of larynxpapillomatosis in human beings (author's transl)].", "content": "Cell culture propagated virus of larynxpapillomatosis of men was purified and concentrated. Ultracentrifugation revealed an approximately 130 S- and a circa 214 S-component. 37 nm and 49 nm particles were found by electron microscope technique, the latter showing a bouyant density in CsCl of 1,34 g/ml. These first experiments demonstrate a close resemblance between this virus and polyomaviruses.", "contents": "[Some physical properties of the virus of larynxpapillomatosis in human beings (author's transl)]. Cell culture propagated virus of larynxpapillomatosis of men was purified and concentrated. Ultracentrifugation revealed an approximately 130 S- and a circa 214 S-component. 37 nm and 49 nm particles were found by electron microscope technique, the latter showing a bouyant density in CsCl of 1,34 g/ml. These first experiments demonstrate a close resemblance between this virus and polyomaviruses."}
{"id": "PMID:215099", "title": "Ultrastructure of the myocardial fibroma.", "content": "The ultrastructure of a myocardial tumor, referred to by a variety of names, which most currently is myocardial fibroma, has been studied. Although the tumor cells did not have the structure associated with protein synthesizing cells or active fibroblasts, there was evidence that they were participating in formation of the abundant stroma rich in collagen and elastic fibers in varying stages of maturity. The morphology of the stromal elements was similar to that in the surrounding myocardium and that described in the \"normal\" heart but differed from the elastica described in fibroelastosis.", "contents": "Ultrastructure of the myocardial fibroma. The ultrastructure of a myocardial tumor, referred to by a variety of names, which most currently is myocardial fibroma, has been studied. Although the tumor cells did not have the structure associated with protein synthesizing cells or active fibroblasts, there was evidence that they were participating in formation of the abundant stroma rich in collagen and elastic fibers in varying stages of maturity. The morphology of the stromal elements was similar to that in the surrounding myocardium and that described in the \"normal\" heart but differed from the elastica described in fibroelastosis."}
{"id": "PMID:215100", "title": "Iron and the liver: subcellular distribution of iron and decreased microsomal cytochrome P-450 in livers of iron-loaded rats.", "content": "To understand better the intracellular iron distribution and metabolic consequences of chronic hepatic iron overload, rats were given large doses of iron dextran or ferric citrate intraperitoneally. They accumulated large quantities of iron within Kupffer cells and hepatocytes. The relative subcellular iron distributions were similar in controls and iron-loaded rats, despite a ten- to 20-fold difference in hepatic iron concentration. Electron microscopy of whole liver and subcellular particulate fractions suggested that iron was present in highest concentration in lysosomes, which were rendered more labile by its presence. Nevertheless, quantitative iron determinations on all subcellular fractions, obtained by two preparative methods, showed that most of the iron was present in the \"soluble\" fraction. The amount of iron in the \"microsomal\" fraction varied, depending on the techniques used for preparation of this fraction. Cytochrome P-450 and total heme concentrations were decreased 40% to 50% in microsomes isolated from iron-loaded livers.", "contents": "Iron and the liver: subcellular distribution of iron and decreased microsomal cytochrome P-450 in livers of iron-loaded rats. To understand better the intracellular iron distribution and metabolic consequences of chronic hepatic iron overload, rats were given large doses of iron dextran or ferric citrate intraperitoneally. They accumulated large quantities of iron within Kupffer cells and hepatocytes. The relative subcellular iron distributions were similar in controls and iron-loaded rats, despite a ten- to 20-fold difference in hepatic iron concentration. Electron microscopy of whole liver and subcellular particulate fractions suggested that iron was present in highest concentration in lysosomes, which were rendered more labile by its presence. Nevertheless, quantitative iron determinations on all subcellular fractions, obtained by two preparative methods, showed that most of the iron was present in the \"soluble\" fraction. The amount of iron in the \"microsomal\" fraction varied, depending on the techniques used for preparation of this fraction. Cytochrome P-450 and total heme concentrations were decreased 40% to 50% in microsomes isolated from iron-loaded livers."}
{"id": "PMID:215101", "title": "Hepatoma in familial cholestatic cirrhosis of childhood: its occurrence in twin brothers.", "content": "Obstructive jaundice, pruritus, and malabsorption developed in twin brothers in infancy. Early liver biopsy specimens showed intracellular and canalicular cholestasis with normal bile ducts. By the age of 3 years, both had cirrhosis and portal hypertension. Each died during the teen years from hepatocellular carcinoma. These brothers represent the tenth reported family with familial cholestatic cirrhosis, and they are the first patients with this syndrome in whom hepatoma developed.", "contents": "Hepatoma in familial cholestatic cirrhosis of childhood: its occurrence in twin brothers. Obstructive jaundice, pruritus, and malabsorption developed in twin brothers in infancy. Early liver biopsy specimens showed intracellular and canalicular cholestasis with normal bile ducts. By the age of 3 years, both had cirrhosis and portal hypertension. Each died during the teen years from hepatocellular carcinoma. These brothers represent the tenth reported family with familial cholestatic cirrhosis, and they are the first patients with this syndrome in whom hepatoma developed."}
{"id": "PMID:215102", "title": "Adenomatous hyperplasia of the liver.", "content": "An unusual case of adenomatous hyperplasia of the liver arose spontaneously in an 82-year-old woman. Massive fatal ascites developed during an eight-week period in the absence of cirrhosis. No drug, chemical, or hormone could be identified as the causative agent. Estrogens may play a role as possible promoters in the growth of hepatic tumors. Identifying liver tumors in women that are not associated with oral contraceptive use is valuable.", "contents": "Adenomatous hyperplasia of the liver. An unusual case of adenomatous hyperplasia of the liver arose spontaneously in an 82-year-old woman. Massive fatal ascites developed during an eight-week period in the absence of cirrhosis. No drug, chemical, or hormone could be identified as the causative agent. Estrogens may play a role as possible promoters in the growth of hepatic tumors. Identifying liver tumors in women that are not associated with oral contraceptive use is valuable."}
{"id": "PMID:215103", "title": "[The malignant fibrous histiocytoma of bone (author's transl)].", "content": "The primary malignant fibrous histiocytoma of bone (Stout) is a rare and autonomous sarcoma of the bone which has to be separated from the osseous sarcoma and the osseous fibrosarcoma. The malignant histiocytoma is morphologically characterized by the storiform pattern of interlacing spindle cell bundles and functionally by the phagocytosis of lipids, glycogen, hemosiderin and hematoidin. Contrary to the osteosarcomas, the main age of osseous histiocytomas are the fifth and sixth decade. Location of predilection are the metaphyses of the long tubular bones. The X-rays show moth-eaten spongiolysis, endosteal erosion and perforation of the cortex. Early metastases in the lungs are frequent. The primary treatment is a surgical one. Case record of a typical malignant osseous histiocytoma from the proximal metaphysis of the left femur with metastases in the lung of a female child, aged 14 years.", "contents": "[The malignant fibrous histiocytoma of bone (author's transl)]. The primary malignant fibrous histiocytoma of bone (Stout) is a rare and autonomous sarcoma of the bone which has to be separated from the osseous sarcoma and the osseous fibrosarcoma. The malignant histiocytoma is morphologically characterized by the storiform pattern of interlacing spindle cell bundles and functionally by the phagocytosis of lipids, glycogen, hemosiderin and hematoidin. Contrary to the osteosarcomas, the main age of osseous histiocytomas are the fifth and sixth decade. Location of predilection are the metaphyses of the long tubular bones. The X-rays show moth-eaten spongiolysis, endosteal erosion and perforation of the cortex. Early metastases in the lungs are frequent. The primary treatment is a surgical one. Case record of a typical malignant osseous histiocytoma from the proximal metaphysis of the left femur with metastases in the lung of a female child, aged 14 years."}
{"id": "PMID:215104", "title": "Synthesis of coreless, probably defective virus particles in cell cultures infected with rotaviruses.", "content": "PK-15 cells infected with pig and lamb rotavirus strains which were not adapted to serial growth in cell cultures were examined by electron microscopy. A major difference between virus morphogenesis in the initial passage in PK-15 cells and in intestinal epithelial cells was the generation of large numbers of coreless virus particles in PK-15 cells. The numbers of coreless particles increased with increasing multiplicity of infection. Infectious virus was synthesized in PK-15 cells, but a variable decrease in infectivity titre occurred between 12 and 24 hours after infection. It is suggested that synthesis of defective interfering particles or an inhibitory substance such as interferon might account for this decrease.", "contents": "Synthesis of coreless, probably defective virus particles in cell cultures infected with rotaviruses. PK-15 cells infected with pig and lamb rotavirus strains which were not adapted to serial growth in cell cultures were examined by electron microscopy. A major difference between virus morphogenesis in the initial passage in PK-15 cells and in intestinal epithelial cells was the generation of large numbers of coreless virus particles in PK-15 cells. The numbers of coreless particles increased with increasing multiplicity of infection. Infectious virus was synthesized in PK-15 cells, but a variable decrease in infectivity titre occurred between 12 and 24 hours after infection. It is suggested that synthesis of defective interfering particles or an inhibitory substance such as interferon might account for this decrease."}
{"id": "PMID:215105", "title": "Permeability changes of plasma and lysosomal membranes in HeLa cells infected with rabbit poxvirus.", "content": "Infection of HeLa-cell monolayer cultures with rabbit poxvirus induces a marked decrease in cell-associated protein and in the activities of lactate dehydrogenase, acid phosphatase, and beta-glucuronidase. This effect begins to occur around 10 hours post-infection (p.i.) and is accompanied by a concomitant rise of these enzyme activities in the culture medium. Only few cells detach from infected monolayers and these cannot account for protein release. Virion release can be inhibited at 4 degrees C, whereas protein release cannot and it seems therefore that these events do not happen by a common mechanism. Moreover, penetration studies with [14C]-sucrose indicate that protein release reflects a true increase in plasma membrane permeability. Using the Gomori stain for acid phosphatase, a release of the enzyme into the cytoplasm around 8 hours p.i. can be confirmed rendering a causative role of lysosomal hydrolases in the pathogenesis of the observed plasma membrane permeability changes possible but not proving it.", "contents": "Permeability changes of plasma and lysosomal membranes in HeLa cells infected with rabbit poxvirus. Infection of HeLa-cell monolayer cultures with rabbit poxvirus induces a marked decrease in cell-associated protein and in the activities of lactate dehydrogenase, acid phosphatase, and beta-glucuronidase. This effect begins to occur around 10 hours post-infection (p.i.) and is accompanied by a concomitant rise of these enzyme activities in the culture medium. Only few cells detach from infected monolayers and these cannot account for protein release. Virion release can be inhibited at 4 degrees C, whereas protein release cannot and it seems therefore that these events do not happen by a common mechanism. Moreover, penetration studies with [14C]-sucrose indicate that protein release reflects a true increase in plasma membrane permeability. Using the Gomori stain for acid phosphatase, a release of the enzyme into the cytoplasm around 8 hours p.i. can be confirmed rendering a causative role of lysosomal hydrolases in the pathogenesis of the observed plasma membrane permeability changes possible but not proving it."}
{"id": "PMID:215106", "title": "Antigenic content of an in vitro cellular immunity reactive cell surface extract of Raji cells.", "content": "Antigenic content of a Raji cell surface extract (TS) was studied by sequential abosrption of rabbit antiserum to this extract with different cells. Anti-TS was first allowed to react exhaustively with human blood cells followed by HeLa cells and human diploid fibroblasts. The residual reactivity was studied by stepwise absorption with an EBV-negative B lymphoblastoid cell line, BJAB, and then with B1--19, a clone derived from EBV transformed BJAB cells. These processes delineated three kinds of reactivities in anti-TS having specificities for antigens on B blasts, EBV-determined cell surface antigen(s) and antigens that are exclusive to Raji cells, respectively. These results are compatible with the heterogeneous protein content of TS and with the results of our earlier in vitro cell-mediated immunity studies using a similar preparation of Raji cell TS.", "contents": "Antigenic content of an in vitro cellular immunity reactive cell surface extract of Raji cells. Antigenic content of a Raji cell surface extract (TS) was studied by sequential abosrption of rabbit antiserum to this extract with different cells. Anti-TS was first allowed to react exhaustively with human blood cells followed by HeLa cells and human diploid fibroblasts. The residual reactivity was studied by stepwise absorption with an EBV-negative B lymphoblastoid cell line, BJAB, and then with B1--19, a clone derived from EBV transformed BJAB cells. These processes delineated three kinds of reactivities in anti-TS having specificities for antigens on B blasts, EBV-determined cell surface antigen(s) and antigens that are exclusive to Raji cells, respectively. These results are compatible with the heterogeneous protein content of TS and with the results of our earlier in vitro cell-mediated immunity studies using a similar preparation of Raji cell TS."}
{"id": "PMID:215107", "title": "A study of Epstein Barr virus receptor activity in cell free extracts of human lymphoblastoid cells.", "content": "Epstein Barr Virus (EBV) receptor activity in cell free extracts is operationally defined as one which causes a reduction in the effective concentration of the early antigen inducing particles of an EBV preparation when the latter is preincubated with the extract before infection. Such activity was detected in the surface extract of Raji cells and to a lesser extent in that of BJAB cells, both of which are B lymphoblastoid cells that are susceptible to infection with EBV. Receptor activity was not detected in similar extracts of P3HR-1 cells and human diploid fibroblasts neither of which are known to be susceptible to EBV infection. Receptor activity in the Raji cell extract was found to be associated with membranous structures. This may have rendered the activity resistant to treatment with trypsin and sonication. The activity was however abrogated if the extract was exposed to neutral detergent. Binding of receptor activity was observed when Raji cell extract was chromatographed on a column of immobilized EBV. Subsequent electrophoretic analysis showed however that this procedure did not result in an appreciable purification of the receptor activity. Neutral detergent treated extract was similarly chromatographed. The resulting eluates did not contain detectable receptor activity but were less heterogeneous in protein content as compared with that of the original extract. It is not certain at present if these EBV binding proteins are involved in the receptor activity of the extract.", "contents": "A study of Epstein Barr virus receptor activity in cell free extracts of human lymphoblastoid cells. Epstein Barr Virus (EBV) receptor activity in cell free extracts is operationally defined as one which causes a reduction in the effective concentration of the early antigen inducing particles of an EBV preparation when the latter is preincubated with the extract before infection. Such activity was detected in the surface extract of Raji cells and to a lesser extent in that of BJAB cells, both of which are B lymphoblastoid cells that are susceptible to infection with EBV. Receptor activity was not detected in similar extracts of P3HR-1 cells and human diploid fibroblasts neither of which are known to be susceptible to EBV infection. Receptor activity in the Raji cell extract was found to be associated with membranous structures. This may have rendered the activity resistant to treatment with trypsin and sonication. The activity was however abrogated if the extract was exposed to neutral detergent. Binding of receptor activity was observed when Raji cell extract was chromatographed on a column of immobilized EBV. Subsequent electrophoretic analysis showed however that this procedure did not result in an appreciable purification of the receptor activity. Neutral detergent treated extract was similarly chromatographed. The resulting eluates did not contain detectable receptor activity but were less heterogeneous in protein content as compared with that of the original extract. It is not certain at present if these EBV binding proteins are involved in the receptor activity of the extract."}
{"id": "PMID:215108", "title": "Photoinactivation of the encephalomyocarditis virus.", "content": "Encephalomyocarditis virus was photoinactivated by a dilution of 1:30,000 neutral red and 70 minutes exposure to light. A dye inactivation of the EMC virus is possible without destruction of its antigenicity. The EMC virus vaccine induced a good immunity response in mice; we did not find any infectious virus.", "contents": "Photoinactivation of the encephalomyocarditis virus. Encephalomyocarditis virus was photoinactivated by a dilution of 1:30,000 neutral red and 70 minutes exposure to light. A dye inactivation of the EMC virus is possible without destruction of its antigenicity. The EMC virus vaccine induced a good immunity response in mice; we did not find any infectious virus."}
{"id": "PMID:215109", "title": "Rapid detection of IgG and IgM antibodies for cytomegalovirus by the enzyme linked immunosorbent assay (ELISA).", "content": "A simple solid phase enzyme immunoassay for the detection of immunoglobulin G and M to cytomegalovirus (CMV) is described. Using this test IgM antibodies to CMV were detected in 0.7 per cent of newborns and regularly after CMV infection in transplant patients, furthermore in these latter patients IgM production was prolonged for several months. For the determination of IgG the enzyme immunoassay was more sensitive than the complement fixation test (CF) and the antibody titres were 4 to 8 fold higher. Since the ELISA test is rapid, specific and unexpensive it can become an acceptable routine diagnostic procedure.", "contents": "Rapid detection of IgG and IgM antibodies for cytomegalovirus by the enzyme linked immunosorbent assay (ELISA). A simple solid phase enzyme immunoassay for the detection of immunoglobulin G and M to cytomegalovirus (CMV) is described. Using this test IgM antibodies to CMV were detected in 0.7 per cent of newborns and regularly after CMV infection in transplant patients, furthermore in these latter patients IgM production was prolonged for several months. For the determination of IgG the enzyme immunoassay was more sensitive than the complement fixation test (CF) and the antibody titres were 4 to 8 fold higher. Since the ELISA test is rapid, specific and unexpensive it can become an acceptable routine diagnostic procedure."}
{"id": "PMID:215110", "title": "[Pulmonary microcarcinoids and their biological significance].", "content": "The results of the analysis of 41 observations of bronchial microcarcinoids (\"tumorlets\") established the regularities of the sex and age distribution of the patients, localizations of the tumours, the patterns of the background processes, histoarchitectonic and cytological variants of tumour foci, different variants of histogenesis as well as the capacity for invasive growth and the occurrence of argirophilic granules in the cytoplasm of tumour cells.", "contents": "[Pulmonary microcarcinoids and their biological significance]. The results of the analysis of 41 observations of bronchial microcarcinoids (\"tumorlets\") established the regularities of the sex and age distribution of the patients, localizations of the tumours, the patterns of the background processes, histoarchitectonic and cytological variants of tumour foci, different variants of histogenesis as well as the capacity for invasive growth and the occurrence of argirophilic granules in the cytoplasm of tumour cells."}
{"id": "PMID:215111", "title": "[Functional morphology of the heart conduction system in acute myocardial infarct].", "content": "The results of histochemical, histoenzymological, and fluorescence microscopy studies of the conductive tissue of the heart in acute myocardial infarction in 30 fatal cases are presented. Focal decrease in redox and hydrolytic enzymes, monoaminoxidase, and cholinesterase in elementa of the conduction system as well as changes in the pattern of fluorescence of the specific muscle cells were found. The intensity of metabolic lesions was more pronounced at early stages of myocardial infarction in those cases where the conducting pathways were proximal to the foci of necrosis.", "contents": "[Functional morphology of the heart conduction system in acute myocardial infarct]. The results of histochemical, histoenzymological, and fluorescence microscopy studies of the conductive tissue of the heart in acute myocardial infarction in 30 fatal cases are presented. Focal decrease in redox and hydrolytic enzymes, monoaminoxidase, and cholinesterase in elementa of the conduction system as well as changes in the pattern of fluorescence of the specific muscle cells were found. The intensity of metabolic lesions was more pronounced at early stages of myocardial infarction in those cases where the conducting pathways were proximal to the foci of necrosis."}
{"id": "PMID:215112", "title": "Isolation of rotavirus from foals with diarrhoea.", "content": "A rotavirus, morphologically similar to other known rotaviruses, was demonstrated in the faeces of 5 foals with diarrhoea on two properties. Four of these 5 samples produced specific intracytoplasmic fluorescence in cell culture when reacted with calf rotavirus antiserum conjugate. Sixteen affected foals from both properties were depressed, did not suckle and became recumbent. Most had a watery diarrhoea which lasted for 3 days and resulted in some dehydration and loss of body condition. Sick foals were separated from their mothers following the onset of diarrhoea and given fluid therapy and antibiotics, but despite these measures 4 of 12 affected foals on one property died. Acute and convalescent sera were collected from 6 foals, and in each case a rise in the titres of complement fixing and neutralising antibodies was demonstrated. Faecal filtrates containing foal rotaviruses were fed to gnotobiotic piglets and the effects compared with those of other rotaviruses. Viral isolates from both properties produced an asymptomatic infection in piglets. This contrasts with the other rotaviruses isolated in Australia that have been shown to cause diarrhoea in gnotobiotic piglets.", "contents": "Isolation of rotavirus from foals with diarrhoea. A rotavirus, morphologically similar to other known rotaviruses, was demonstrated in the faeces of 5 foals with diarrhoea on two properties. Four of these 5 samples produced specific intracytoplasmic fluorescence in cell culture when reacted with calf rotavirus antiserum conjugate. Sixteen affected foals from both properties were depressed, did not suckle and became recumbent. Most had a watery diarrhoea which lasted for 3 days and resulted in some dehydration and loss of body condition. Sick foals were separated from their mothers following the onset of diarrhoea and given fluid therapy and antibiotics, but despite these measures 4 of 12 affected foals on one property died. Acute and convalescent sera were collected from 6 foals, and in each case a rise in the titres of complement fixing and neutralising antibodies was demonstrated. Faecal filtrates containing foal rotaviruses were fed to gnotobiotic piglets and the effects compared with those of other rotaviruses. Viral isolates from both properties produced an asymptomatic infection in piglets. This contrasts with the other rotaviruses isolated in Australia that have been shown to cause diarrhoea in gnotobiotic piglets."}
{"id": "PMID:215118", "title": "The subcellular location, maturation and response to increased plasma glucagon of ruthenium red-insensitive calcium-ion transport in rat liver.", "content": "1. The subcellular distribution and maturation of Ruthenium Red-insensitive Ca(2+) transport activity were determined in livers of rats ranging in age from 3 days pre-term to 10 weeks of adult life and compared with those of glucose 6-phosphatase, 5'-nucleotidase and Ruthenium Red-sensitive Ca(2+) transport. Initial rates of Ruthenium Red-insensitive Ca(2+) transport were highest in those fractions enriched in glucose 6-phosphatase, i.e. the microsomal fraction; this fraction was devoid of Ruthenium Red-sensitive Ca(2+) transport activity. Although the heaviest fraction (nuclear) contained significant amounts of 5'-nucleotidase activity it was devoid of Ruthenium Red-insensitive Ca(2+) transport activity. 2. Foetal rat liver contain minimal amounts of Ruthenium Red-insensitive Ca(2+) transport activity, glucose 6-phosphatase and 5'-nucleotidase activities. These begin to be expressed concomitantly soon after birth; Ruthenium Red-insensitive Ca(2+) transport is maximal by 3 to 4 days and remains so for up to at least 10 weeks of adult life. Glucose 6-phosphatase also reaches a peak at 3-4 days, but then rapidly decreases to approach adult values. Maximal activity of 5'-nucleotidase in the microsomal and nuclear fractions is seen about 4-6 days after birth; this enzyme activity remains increased for up to about 10 days and then falls, but not as rapidly as glucose 6-phosphatase. It is tentatively suggested that the bulk of the Ruthenium Red-insensitive Ca(2+) transport is attributable to the system derived from the endoplasmic reticulum. 3. Administration of glucagon to adult rats enhances by 2-3-fold the initial rate of Ruthenium Red-insensitive Ca(2+) transport in the intermediate but not the microsomal fraction. The hormone-induced effect is fully suppressed by co-administration of puromycin, is dose-dependent with half-maximal response at approx. 1mug of glucagon/100g body wt. and time-dependent exhibiting a half-maximal response about 1h after administration of the hormone. 4. Ruthenium Red-insensitive Ca(2+) transport in the post-mitochondrial fraction of foetal liver also responds to the administration in situ of glucagon. The response, which also is prevented by co-administration of puromycin, is maximal in those foetuses nearing term. The suggestion is made that these effects of the hormone on Ruthenium Red-insensitive Ca(2+) transport are an integral part of the physiological network in the liver cell.", "contents": "The subcellular location, maturation and response to increased plasma glucagon of ruthenium red-insensitive calcium-ion transport in rat liver. 1. The subcellular distribution and maturation of Ruthenium Red-insensitive Ca(2+) transport activity were determined in livers of rats ranging in age from 3 days pre-term to 10 weeks of adult life and compared with those of glucose 6-phosphatase, 5'-nucleotidase and Ruthenium Red-sensitive Ca(2+) transport. Initial rates of Ruthenium Red-insensitive Ca(2+) transport were highest in those fractions enriched in glucose 6-phosphatase, i.e. the microsomal fraction; this fraction was devoid of Ruthenium Red-sensitive Ca(2+) transport activity. Although the heaviest fraction (nuclear) contained significant amounts of 5'-nucleotidase activity it was devoid of Ruthenium Red-insensitive Ca(2+) transport activity. 2. Foetal rat liver contain minimal amounts of Ruthenium Red-insensitive Ca(2+) transport activity, glucose 6-phosphatase and 5'-nucleotidase activities. These begin to be expressed concomitantly soon after birth; Ruthenium Red-insensitive Ca(2+) transport is maximal by 3 to 4 days and remains so for up to at least 10 weeks of adult life. Glucose 6-phosphatase also reaches a peak at 3-4 days, but then rapidly decreases to approach adult values. Maximal activity of 5'-nucleotidase in the microsomal and nuclear fractions is seen about 4-6 days after birth; this enzyme activity remains increased for up to about 10 days and then falls, but not as rapidly as glucose 6-phosphatase. It is tentatively suggested that the bulk of the Ruthenium Red-insensitive Ca(2+) transport is attributable to the system derived from the endoplasmic reticulum. 3. Administration of glucagon to adult rats enhances by 2-3-fold the initial rate of Ruthenium Red-insensitive Ca(2+) transport in the intermediate but not the microsomal fraction. The hormone-induced effect is fully suppressed by co-administration of puromycin, is dose-dependent with half-maximal response at approx. 1mug of glucagon/100g body wt. and time-dependent exhibiting a half-maximal response about 1h after administration of the hormone. 4. Ruthenium Red-insensitive Ca(2+) transport in the post-mitochondrial fraction of foetal liver also responds to the administration in situ of glucagon. The response, which also is prevented by co-administration of puromycin, is maximal in those foetuses nearing term. The suggestion is made that these effects of the hormone on Ruthenium Red-insensitive Ca(2+) transport are an integral part of the physiological network in the liver cell."}
{"id": "PMID:215119", "title": "The adenylate cyclase-activating activity of cholera toxin is not associated with a nicotinamide--adenine dinucleotide glycohydrolase activity.", "content": "The NAD+ glycohydrolase activity of cholera-toxin samples can be separated from their adenylate cyclase-activating activity by polyacrylamide-gel electrophoresis and is inhibited by sodium dodecyl sulphate (which does not inhibit the action of toxin on cells), but not by antibodies to pure toxin. It is therefore probably not a true property of the toxin.", "contents": "The adenylate cyclase-activating activity of cholera toxin is not associated with a nicotinamide--adenine dinucleotide glycohydrolase activity. The NAD+ glycohydrolase activity of cholera-toxin samples can be separated from their adenylate cyclase-activating activity by polyacrylamide-gel electrophoresis and is inhibited by sodium dodecyl sulphate (which does not inhibit the action of toxin on cells), but not by antibodies to pure toxin. It is therefore probably not a true property of the toxin."}
{"id": "PMID:215120", "title": "Dibutyryladenosine 3':5'-cyclic monophosphate-mediated changes in rat cells involve macromolecular alterations in vinblastine-precipitable proteins.", "content": "ts-NT3-KR rat cell cultures show the loss of three components in the molecular-weight region 200,000--250,000 when exposed to dibutyryl cyclic AMP, under conditions of both restriction and expression of the transformed phenotype. Vinblastine is able to precipitate preferentially from control cultures the species that are decreased by exposure to the cyclic nucleotide. Serum-starved cultures exposed to dibutyryl cyclic AMP reveal differences in their vinblastine precipitates, depending on whether the expression of the transformation phenotype is restricted or not.", "contents": "Dibutyryladenosine 3':5'-cyclic monophosphate-mediated changes in rat cells involve macromolecular alterations in vinblastine-precipitable proteins. ts-NT3-KR rat cell cultures show the loss of three components in the molecular-weight region 200,000--250,000 when exposed to dibutyryl cyclic AMP, under conditions of both restriction and expression of the transformed phenotype. Vinblastine is able to precipitate preferentially from control cultures the species that are decreased by exposure to the cyclic nucleotide. Serum-starved cultures exposed to dibutyryl cyclic AMP reveal differences in their vinblastine precipitates, depending on whether the expression of the transformation phenotype is restricted or not."}
{"id": "PMID:215121", "title": "A simple assay for adenylate cyclase in intact cells by affinity elution chromatography.", "content": "A method using the principle of affinity elution chromatography is described for the assay of adenylate cyclase in intact human platelets. By incubating platelet-rich plasma in the presence of radioactively labelled adenine, the ATP pool of the cells was prelabelled. Formation of labelled cyclic AMP from ATP was determined by extracting the platelets with HC1O4. After removal of the latter as KC1O4, the extract containing cyclic AMP and other adenine nucleotides was adsorbed in a NN-diethyl-N-2-hydroxypropylamino (QAE)-cellulose column. The column was washed, and subsequently cyclic AMP was specifically eluted with a cyclic AMP-dependent protein kinase and the radioactivity of the eluate was determined.", "contents": "A simple assay for adenylate cyclase in intact cells by affinity elution chromatography. A method using the principle of affinity elution chromatography is described for the assay of adenylate cyclase in intact human platelets. By incubating platelet-rich plasma in the presence of radioactively labelled adenine, the ATP pool of the cells was prelabelled. Formation of labelled cyclic AMP from ATP was determined by extracting the platelets with HC1O4. After removal of the latter as KC1O4, the extract containing cyclic AMP and other adenine nucleotides was adsorbed in a NN-diethyl-N-2-hydroxypropylamino (QAE)-cellulose column. The column was washed, and subsequently cyclic AMP was specifically eluted with a cyclic AMP-dependent protein kinase and the radioactivity of the eluate was determined."}
{"id": "PMID:215122", "title": "The interaction between mitochondrial NADH-ubiquinone oxidoreductase and ubiquinol-cytochrome c oxidoreductase. Evidence for stoicheiometric association.", "content": "1. The NADH-ubiquinone oxidoreductase complex (Complex I) and the ubiquinol-cytochrome c oxidoreductase complex (Complex III) combine in a 1:1 molar ratio to give NADH-cytochrome c oxidoreductase (Complex I-Complex III). 2. Experiments on the inhibition of the NADH-cytochrome c oxidoreductase activity of mixtures of Complexes I and III by rotenone and antimycin indicate that electron transfer between a unit of Complex I-Complex III and extra molecules of Complexes I or III does not contribute to the overall rate of cytochrome c reduction. 3. The reduction by NADH of the cytochrome b of mixtures of Complexes I and III is biphasic. The extents of the fast and slow phases of reduction are determined by the proportion of the total Complex III specifically associated with Complex I. 4. Activation-energy measurements suggest that the structural features of the Complex I-Complex III unit promote oxidoreduction of endogenous ubiquinone-10.", "contents": "The interaction between mitochondrial NADH-ubiquinone oxidoreductase and ubiquinol-cytochrome c oxidoreductase. Evidence for stoicheiometric association. 1. The NADH-ubiquinone oxidoreductase complex (Complex I) and the ubiquinol-cytochrome c oxidoreductase complex (Complex III) combine in a 1:1 molar ratio to give NADH-cytochrome c oxidoreductase (Complex I-Complex III). 2. Experiments on the inhibition of the NADH-cytochrome c oxidoreductase activity of mixtures of Complexes I and III by rotenone and antimycin indicate that electron transfer between a unit of Complex I-Complex III and extra molecules of Complexes I or III does not contribute to the overall rate of cytochrome c reduction. 3. The reduction by NADH of the cytochrome b of mixtures of Complexes I and III is biphasic. The extents of the fast and slow phases of reduction are determined by the proportion of the total Complex III specifically associated with Complex I. 4. Activation-energy measurements suggest that the structural features of the Complex I-Complex III unit promote oxidoreduction of endogenous ubiquinone-10."}
{"id": "PMID:215123", "title": "The interaction between mitochondrial NADH-ubiquinone oxidoreductase and ubiquinol-cytochrome c oxidoreductase. Restoration of ubiquinone-pool behaviour.", "content": "1. In the inner mitochondrial membrane, dehydrogenases and cytochromes appear to act independently of each other, and electron transport has been proposed to occur through a mobile pool of ubiquinone-10 molecules [Kr\u00f6ger & Klingenberg (1973) Eur. J. Biochem. 34, 358--368]. 2. Such behaviour can be restored to the interaction between purified Complex I and Complex III by addition of phospholipid and ubiquinone-10 to a concentrated mixture of the Complexes before dilution. 3. A model is proposed for the interaction of Complex I with Complex III in the natural membrane that emphasizes relative mobility of the Complexes rather than ubiquinone-10. Electron transfer occurs only through stoicheiometric Complex I-Complex III units, which, however, are formed and re-formed at rates higher than the rate of electron transfer.", "contents": "The interaction between mitochondrial NADH-ubiquinone oxidoreductase and ubiquinol-cytochrome c oxidoreductase. Restoration of ubiquinone-pool behaviour. 1. In the inner mitochondrial membrane, dehydrogenases and cytochromes appear to act independently of each other, and electron transport has been proposed to occur through a mobile pool of ubiquinone-10 molecules [Kr\u00f6ger & Klingenberg (1973) Eur. J. Biochem. 34, 358--368]. 2. Such behaviour can be restored to the interaction between purified Complex I and Complex III by addition of phospholipid and ubiquinone-10 to a concentrated mixture of the Complexes before dilution. 3. A model is proposed for the interaction of Complex I with Complex III in the natural membrane that emphasizes relative mobility of the Complexes rather than ubiquinone-10. Electron transfer occurs only through stoicheiometric Complex I-Complex III units, which, however, are formed and re-formed at rates higher than the rate of electron transfer."}
{"id": "PMID:215124", "title": "Prostaglandin receptors on human platelets. Structure-activity relationships of stimulatory prostaglandins.", "content": "1. Synthetic analogues of prostaglandins E2 or F2a (monocyclic bisenoic prostaglandins), like the endogenous prostaglandin endoperoxides (prostaglandins G2 and H2) from platelets, and like synthetic analogues of prostaglandin H2 (bicyclic bisenoic prostaglandins), can induce aggregation of human platelets, although prostaglandins E2 and F2a themselves are inactive. 2. All the prostanoid compounds that induce platelet aggregation release 5-hydroxytryptamine from platelet dense bodies, but do not release beta-N-acetylglucosaminidase from lysosomal granules. Arachidonic acid evokes a similar response. 3. All endoperoxide analogues tested (bicyclic compounds) were powerful platelet stimulants, and all active compounds (whether mono- or bi-cyclid) apparently acted via the same receptor as the endogenous prostaglandin endoperoxides. 4. The nature and stereospecificity of substituents at positions 11 and 15 (or 16) on prostaglandin E2 are critical determinants for platelet-stimulating activity: deoxy substitution at position 11 plus methylation at position 15 (or 16) produces a potent stimulant, particularly if the groups around C-15 are in the S configuration. 5. The effects of these structural modifications are apparently due to, at least in part, a change in side-chain conformation.", "contents": "Prostaglandin receptors on human platelets. Structure-activity relationships of stimulatory prostaglandins. 1. Synthetic analogues of prostaglandins E2 or F2a (monocyclic bisenoic prostaglandins), like the endogenous prostaglandin endoperoxides (prostaglandins G2 and H2) from platelets, and like synthetic analogues of prostaglandin H2 (bicyclic bisenoic prostaglandins), can induce aggregation of human platelets, although prostaglandins E2 and F2a themselves are inactive. 2. All the prostanoid compounds that induce platelet aggregation release 5-hydroxytryptamine from platelet dense bodies, but do not release beta-N-acetylglucosaminidase from lysosomal granules. Arachidonic acid evokes a similar response. 3. All endoperoxide analogues tested (bicyclic compounds) were powerful platelet stimulants, and all active compounds (whether mono- or bi-cyclid) apparently acted via the same receptor as the endogenous prostaglandin endoperoxides. 4. The nature and stereospecificity of substituents at positions 11 and 15 (or 16) on prostaglandin E2 are critical determinants for platelet-stimulating activity: deoxy substitution at position 11 plus methylation at position 15 (or 16) produces a potent stimulant, particularly if the groups around C-15 are in the S configuration. 5. The effects of these structural modifications are apparently due to, at least in part, a change in side-chain conformation."}
{"id": "PMID:215125", "title": "Subcellular structure of bovine thyroid gland. The localization of the peroxidase activity in bovine thyroid.", "content": "1. After differential pelleting of bovine thyroid tissue the highest relative specific activities for plasma membrane markers are found in the L fraction whereas those for peroxidase activities (p-phenylenediamine, guaiacol and 3,3'-diaminobenizidine tetrachloride peroxidases) are found in the M fraction. 2. When M + L fractions were subjected to buoyant-density equilibration in a HS zonal rotor all peroxidases show different profiles. The guaiacol peroxidase activity always follows the distribution of glucose 6-phosphatase. 3. When a Sb fraction is subjected to Sepharose 2B chromatography three major peaks are obtained. The first, eluted at the void volume, consists of membranous material and contains most of the guaiacol peroxidase activity. Most of the protein (probably thyroglobulin) is eluted with the second peak. Solubilized enzymes are recovered in the third peak. 4. p-Phenylenediamine peroxidase activity penetrates into the gel on polyacrylamidegel electrophoresis, whereas guaiacol peroxidase activity remains at the sample zone. 5. DEAE-Sephadex A-50 chromatography resolves the peroxidase activities into two peaks, displaying different relative amounts of the different enzymic activities in each peak. 6. The peroxidase activities may be due to the presence of different proteins. A localization of guaiacol peroxidase in rough-endoplasmic-reticulum membranes (or in membranes related to them) seems very likely.", "contents": "Subcellular structure of bovine thyroid gland. The localization of the peroxidase activity in bovine thyroid. 1. After differential pelleting of bovine thyroid tissue the highest relative specific activities for plasma membrane markers are found in the L fraction whereas those for peroxidase activities (p-phenylenediamine, guaiacol and 3,3'-diaminobenizidine tetrachloride peroxidases) are found in the M fraction. 2. When M + L fractions were subjected to buoyant-density equilibration in a HS zonal rotor all peroxidases show different profiles. The guaiacol peroxidase activity always follows the distribution of glucose 6-phosphatase. 3. When a Sb fraction is subjected to Sepharose 2B chromatography three major peaks are obtained. The first, eluted at the void volume, consists of membranous material and contains most of the guaiacol peroxidase activity. Most of the protein (probably thyroglobulin) is eluted with the second peak. Solubilized enzymes are recovered in the third peak. 4. p-Phenylenediamine peroxidase activity penetrates into the gel on polyacrylamidegel electrophoresis, whereas guaiacol peroxidase activity remains at the sample zone. 5. DEAE-Sephadex A-50 chromatography resolves the peroxidase activities into two peaks, displaying different relative amounts of the different enzymic activities in each peak. 6. The peroxidase activities may be due to the presence of different proteins. A localization of guaiacol peroxidase in rough-endoplasmic-reticulum membranes (or in membranes related to them) seems very likely."}
{"id": "PMID:215126", "title": "Activities and some properties of 5'-nucleotidase, adenosine kinase and adenosine deaminase in tissues from vertebrates and invertebrates in relation to the control of the concentration and the physiological role of adenosine.", "content": "1. The maximal activities of 5'-nucleotidase, adenosine kinase and adenosine deaminase together with the Km values for their respective substrates were measured in muscle, nervous tissue and liver from a large range of animals to provide information on the mechanism of control of adenosine concentration in the tissues. 2. Detailed evidence that the methods used were optimal for the extraction and assay of these enzymes has been deposited as Supplementary Publication SUP 50088 (16pages) at the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K.,from whom copies can be obtained on the terms indicated in Biochem. J. (1978), 169, 5. This evidence includes the effects of pH and temperature on the activities of the enzymes. 3. In many tissues, the activities of 5'-nucleotidase were considerably higher than the sum of the activities of adenosine kinase and deaminase, which suggests that the activity of the nucleotidase must be markedly inhibited in vivo so that adenosine does not accumulate. In the tissues in which comparison is possible, the Km of the nucleotidase is higher than the AMP content of the tissue, and since some of the latter may be bound within the cell, the low concentration of substrate may, in part, be responsible for a low activity in vivo. 4. In most tissues and animals investigated, the values of the Km of adenosine kinase for adenosine are between one and two orders of magnitude lower than those for the deaminase. It is suggested that 5'-nucleotidase and adenosine kinase are simultaneously active so that a substrate cycle between AMP and adenosine is produced: the difference in Km values between kinase and deaminase indicates that, via the cycle, small changes in activity of kinase or nucleotidase produce large changes in adenosine concentration. 5. The activities of adenosine kinase or deaminase from vertebrate muscles are inversely correlated with the activities of phosphorylase in these muscles. Since the magnitude of the latter activities are indicative of the anaerobic nature of muscles, this negative correlation supports the hypothesis that an important role of adenosine is the regulation of blood flow in the aerobic muscles.", "contents": "Activities and some properties of 5'-nucleotidase, adenosine kinase and adenosine deaminase in tissues from vertebrates and invertebrates in relation to the control of the concentration and the physiological role of adenosine. 1. The maximal activities of 5'-nucleotidase, adenosine kinase and adenosine deaminase together with the Km values for their respective substrates were measured in muscle, nervous tissue and liver from a large range of animals to provide information on the mechanism of control of adenosine concentration in the tissues. 2. Detailed evidence that the methods used were optimal for the extraction and assay of these enzymes has been deposited as Supplementary Publication SUP 50088 (16pages) at the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K.,from whom copies can be obtained on the terms indicated in Biochem. J. (1978), 169, 5. This evidence includes the effects of pH and temperature on the activities of the enzymes. 3. In many tissues, the activities of 5'-nucleotidase were considerably higher than the sum of the activities of adenosine kinase and deaminase, which suggests that the activity of the nucleotidase must be markedly inhibited in vivo so that adenosine does not accumulate. In the tissues in which comparison is possible, the Km of the nucleotidase is higher than the AMP content of the tissue, and since some of the latter may be bound within the cell, the low concentration of substrate may, in part, be responsible for a low activity in vivo. 4. In most tissues and animals investigated, the values of the Km of adenosine kinase for adenosine are between one and two orders of magnitude lower than those for the deaminase. It is suggested that 5'-nucleotidase and adenosine kinase are simultaneously active so that a substrate cycle between AMP and adenosine is produced: the difference in Km values between kinase and deaminase indicates that, via the cycle, small changes in activity of kinase or nucleotidase produce large changes in adenosine concentration. 5. The activities of adenosine kinase or deaminase from vertebrate muscles are inversely correlated with the activities of phosphorylase in these muscles. Since the magnitude of the latter activities are indicative of the anaerobic nature of muscles, this negative correlation supports the hypothesis that an important role of adenosine is the regulation of blood flow in the aerobic muscles."}
{"id": "PMID:215127", "title": "Maximum activities and effects of fructose bisphosphate on pyruvate kinase from muscles of vertebrates and invertebrates in relation to the control of glycolysis.", "content": "1. Comparison of the maximum activities of pyruvate kinase with those of phosphofructokinase in a large number of muscles from invertebrates and vertebrates indicates that, in general, in any individual muscle, the activity of pyruvate kinase is only severalfold higher than that of phosphofructokinase. This is consistent with the suggestion, based on mass-action ratio data, that the pyruvate kinase reaction is non-equilibrium in muscle. However, the range of activities of pyruvate kinase in these muscles is considerably larger than that of phosphofructokinase. This difference almost disappears if the enzyme activities from muscles that are known to possess an anaerobic ;succinate pathway' are excluded. It is suggested that, in these muscles, phosphofructokinase provides glycolytic residues for both pyruvate kinase (i.e. glycolysis) and phosphoenolpyruvate carboxykinase (i.e. the succinate pathway). This is supported by a negative correlation between the activity ratio, pyruvate kinase/phosphofructokinase, and the activities of nucleoside diphosphokinase in these muscles, since high activities of nucleoside diphosphokinase are considered to indicate the presence of the succinate pathway. 2. The effect of fructose bisphosphate on the activities of pyruvate kinase from many different muscles was studied. The stimulatory effect of fructose bisphosphate appears to be lost whenever an efficient system for supply of oxygen to the muscles is developed (e.g. insects, squids, birds and mammals). This suggests that activation of pyruvate kinase is important in the co-ordinated regulation of glycolysis in anaerobic or hypoxic conditions, when the change in glycolytic flux during the transition from rest to activity needs to be large in order to provide sufficient energy for the contractile activity. However, lack of this effect in the anaerobic muscles of the birds and mammals suggests that another metabolic control may exist for avian and mammalian pyruvate kinase in these muscles.", "contents": "Maximum activities and effects of fructose bisphosphate on pyruvate kinase from muscles of vertebrates and invertebrates in relation to the control of glycolysis. 1. Comparison of the maximum activities of pyruvate kinase with those of phosphofructokinase in a large number of muscles from invertebrates and vertebrates indicates that, in general, in any individual muscle, the activity of pyruvate kinase is only severalfold higher than that of phosphofructokinase. This is consistent with the suggestion, based on mass-action ratio data, that the pyruvate kinase reaction is non-equilibrium in muscle. However, the range of activities of pyruvate kinase in these muscles is considerably larger than that of phosphofructokinase. This difference almost disappears if the enzyme activities from muscles that are known to possess an anaerobic ;succinate pathway' are excluded. It is suggested that, in these muscles, phosphofructokinase provides glycolytic residues for both pyruvate kinase (i.e. glycolysis) and phosphoenolpyruvate carboxykinase (i.e. the succinate pathway). This is supported by a negative correlation between the activity ratio, pyruvate kinase/phosphofructokinase, and the activities of nucleoside diphosphokinase in these muscles, since high activities of nucleoside diphosphokinase are considered to indicate the presence of the succinate pathway. 2. The effect of fructose bisphosphate on the activities of pyruvate kinase from many different muscles was studied. The stimulatory effect of fructose bisphosphate appears to be lost whenever an efficient system for supply of oxygen to the muscles is developed (e.g. insects, squids, birds and mammals). This suggests that activation of pyruvate kinase is important in the co-ordinated regulation of glycolysis in anaerobic or hypoxic conditions, when the change in glycolytic flux during the transition from rest to activity needs to be large in order to provide sufficient energy for the contractile activity. However, lack of this effect in the anaerobic muscles of the birds and mammals suggests that another metabolic control may exist for avian and mammalian pyruvate kinase in these muscles."}
{"id": "PMID:215128", "title": "Stimulation of triacylglycerol synthesis in rat adipocytes by plasma very-low-density lipoproteins.", "content": "The effect of human plasma lipoproteins on lipogenesis from glucose has been studied in isolated rat adipocytes. The very-low-density lipoproteins increased lipogenesis specifically, whereas low-density lipoproteins and high-density lipoproteins were without effect. Such stimulation could be reproduced with partially delipidated very-low-density lipoproteins. Nod-esterified fatty acids and glycerol were also without effect. Pretreatment of the adipocytes with trypsin did not alter the effect of very-low-density lipoprotein. The presence of Ca2+ was required for the full activation of lipogenesis. The synthesis of acylglycerol fatty acids and of acylglycerol glycerol were equally increased. The effect of very-low-density lipoprotein was not additive to that of insulin. It is suggested that very-low-density lipoprotein may directly stimulate lipogenesis in fat-cells, particularly in states when the lipoproteins are present at high concentration in the circulation.", "contents": "Stimulation of triacylglycerol synthesis in rat adipocytes by plasma very-low-density lipoproteins. The effect of human plasma lipoproteins on lipogenesis from glucose has been studied in isolated rat adipocytes. The very-low-density lipoproteins increased lipogenesis specifically, whereas low-density lipoproteins and high-density lipoproteins were without effect. Such stimulation could be reproduced with partially delipidated very-low-density lipoproteins. Nod-esterified fatty acids and glycerol were also without effect. Pretreatment of the adipocytes with trypsin did not alter the effect of very-low-density lipoprotein. The presence of Ca2+ was required for the full activation of lipogenesis. The synthesis of acylglycerol fatty acids and of acylglycerol glycerol were equally increased. The effect of very-low-density lipoprotein was not additive to that of insulin. It is suggested that very-low-density lipoprotein may directly stimulate lipogenesis in fat-cells, particularly in states when the lipoproteins are present at high concentration in the circulation."}
{"id": "PMID:215129", "title": "Calcium-dependent inhibition of protein synthesis in rat parotid gland.", "content": "1. Protein synthesis in the rat parotid gland in vitro was studied by measuring the incorporation of [3H]phenylalanine into  trichloroacetic acid-insoluble proteins. In the unstimulated gland, the rate of incorporation was dependent on the phenylalanine concentration in the medium and proceeded linearly for up to 3h. 2. Adrenaline, carbamoylcholine, phenylephrine and ionophore  A23187 inhibited the incorporation of [3H]phenylalanine into acid-insoluble protein; isoprenaline, dibutyryl cyclic AMP and 8-bromo-cyclic GMP were inactive. 3. Inhibition by adrenaline and carbamoylcholine but not by ionophore A23187  required extracellular Ca2+. 4. Both adrenaline and carbamoylcholine increased the magnitude of the acid-soluble [3H]phenylalanine pool at 10 micrometer extracellular phenylalanine, but had no effect if the phenylalanine concentration was increased to 200 micrometer. 5. There was no correlation between cellular ATP content and the observed inhibition of protein synthesis. 6. Our results suggest that both alpha-adrenergic and cholinergic receptors may play a role in the regulation of protein synthesis in the rat parotid gland, and that their effects are mediated by a rise in intracellular free Ca2+.", "contents": "Calcium-dependent inhibition of protein synthesis in rat parotid gland. 1. Protein synthesis in the rat parotid gland in vitro was studied by measuring the incorporation of [3H]phenylalanine into  trichloroacetic acid-insoluble proteins. In the unstimulated gland, the rate of incorporation was dependent on the phenylalanine concentration in the medium and proceeded linearly for up to 3h. 2. Adrenaline, carbamoylcholine, phenylephrine and ionophore  A23187 inhibited the incorporation of [3H]phenylalanine into acid-insoluble protein; isoprenaline, dibutyryl cyclic AMP and 8-bromo-cyclic GMP were inactive. 3. Inhibition by adrenaline and carbamoylcholine but not by ionophore A23187  required extracellular Ca2+. 4. Both adrenaline and carbamoylcholine increased the magnitude of the acid-soluble [3H]phenylalanine pool at 10 micrometer extracellular phenylalanine, but had no effect if the phenylalanine concentration was increased to 200 micrometer. 5. There was no correlation between cellular ATP content and the observed inhibition of protein synthesis. 6. Our results suggest that both alpha-adrenergic and cholinergic receptors may play a role in the regulation of protein synthesis in the rat parotid gland, and that their effects are mediated by a rise in intracellular free Ca2+."}
{"id": "PMID:215130", "title": "Effect of corticotropin treatment in vivo on the synthesis of a specific adrenal cytosolic protein. Characterization by dual-labelling technique and polyacrylamide-gel electrophoresis.", "content": "The effect of corticotropin in vivo on total and specific protein synthesis in the adrenal was studied. Adrenal slices from control and corticotropin-treated animals were incubated with [14C]- and [3H]-leucine respectively, followed by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis of subcellular components. With this sensitive dual-labelling technique the following results were obtained. There was a general trophic effect on most adrenal proteins, but corticotropin produced a marked stimulation of a specific adrenal cytosolic protein. This protein has mol.wt. approx. 30 000 and pI 5.5. Corticotropin increased the incorporation of labelled leucine into proteins within 4 h, but no effect was observed before 2 h and after 16 h there was no further increase. These data suggest that this protein is not involved in the corticosteroidogenic action of corticotropin, but rather in the trophic action of this hormone.", "contents": "Effect of corticotropin treatment in vivo on the synthesis of a specific adrenal cytosolic protein. Characterization by dual-labelling technique and polyacrylamide-gel electrophoresis. The effect of corticotropin in vivo on total and specific protein synthesis in the adrenal was studied. Adrenal slices from control and corticotropin-treated animals were incubated with [14C]- and [3H]-leucine respectively, followed by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis of subcellular components. With this sensitive dual-labelling technique the following results were obtained. There was a general trophic effect on most adrenal proteins, but corticotropin produced a marked stimulation of a specific adrenal cytosolic protein. This protein has mol.wt. approx. 30 000 and pI 5.5. Corticotropin increased the incorporation of labelled leucine into proteins within 4 h, but no effect was observed before 2 h and after 16 h there was no further increase. These data suggest that this protein is not involved in the corticosteroidogenic action of corticotropin, but rather in the trophic action of this hormone."}
{"id": "PMID:215131", "title": "Studies on the assembly of the rat lens capsule. Biosynthesis and partial characterization of the collagenous components.", "content": "1. Isolated rat lens capsules synthesized hydroxy[3H]proline-containing polypeptides when incubated with [3H]proline. 2. The collagenous polypeptides synthesized during a 2 h incubation were analyzed by both gel-filtration chromatography and sodium dodecyl sulphate/polyacrylamide-gel electrophoresis and shown to have an apparent mol.wt. of approx. 180,000. 3. No evidence was obtained for conversion of these polypeptides into a lower-molecular-weight species in experiments where capsules were labelled for 2 h and chased with non-radioactive proline for up to 22 h. However, a time-dependent incorporation of the 180,000-mol.wt. species into a larger collagenous component was observed and this could be prevented by the inclusion of beta-aminopropionitrile in the incubation medium. 4. The radioactive components synthesized by the capsules correspond to subunits of the intact lens capsule and the direct incorporation of the polypeptide of mol.wt. 180,000 into deoxycholate-insoluble basement membrane was demonstrated.", "contents": "Studies on the assembly of the rat lens capsule. Biosynthesis and partial characterization of the collagenous components. 1. Isolated rat lens capsules synthesized hydroxy[3H]proline-containing polypeptides when incubated with [3H]proline. 2. The collagenous polypeptides synthesized during a 2 h incubation were analyzed by both gel-filtration chromatography and sodium dodecyl sulphate/polyacrylamide-gel electrophoresis and shown to have an apparent mol.wt. of approx. 180,000. 3. No evidence was obtained for conversion of these polypeptides into a lower-molecular-weight species in experiments where capsules were labelled for 2 h and chased with non-radioactive proline for up to 22 h. However, a time-dependent incorporation of the 180,000-mol.wt. species into a larger collagenous component was observed and this could be prevented by the inclusion of beta-aminopropionitrile in the incubation medium. 4. The radioactive components synthesized by the capsules correspond to subunits of the intact lens capsule and the direct incorporation of the polypeptide of mol.wt. 180,000 into deoxycholate-insoluble basement membrane was demonstrated."}
{"id": "PMID:215132", "title": "Effects of glucagon and N6O2'-dibutyryladenosine 3':5'-cyclic monophosphate on calcium transport in isolated rat liver mitochondria.", "content": "1. The administration of glucagon to fed rats by intraperitoneal injection, or the perfusion of livers from fed rats with glucagon by the method of Mortimore [Mortimore (1963) Am.J. Physiol. 204, 699--704] was associated with increases of 15- and 5-fold respectively, in the time for which a given load of exogenous Ca2+ is retained by mitochondria subsequently isolated from the liver. This effect of glucagon was (a) also induced by N6O2'-dibutyryl cyclic AMP, (b) completely blocked by cycloheximide, (c) relatively slow in onset (15--60 min) and (d) associated with a stimulation of about 20% in the rates of ADP-stimulated oxygen utilization and Ca2+ transport measured in the presence of succinate. 2. Perfusion of livers with glucagon resulted in the isolation of mitochandria which showed a 50% increase, no significant change and a 40% increase in the concentrations of endogenous Ca, Mg and Pi respectively, when compared with mitochondria isolated from control perfused livers. 3. The administration of insulin or adrenaline to fed rats induced increases of 10- and 8-fold respectively, in the time for which Ca2+ is retained by isolated liver mitochondria. Perfusion of livers with insulin had no effect on mitochondrial Ca2+ retention time. 4. The perfusion of livers from starved rats with glucagon, or the administration of either glucagon or insulin to starved rats, increased by about 2.5- and 15-fold respectively, the time for which isolated mitochondria retain Ca2+. 5. Mechanisms which may be responsible for the observed alterations in Ca2+-retention time are discussed.", "contents": "Effects of glucagon and N6O2'-dibutyryladenosine 3':5'-cyclic monophosphate on calcium transport in isolated rat liver mitochondria. 1. The administration of glucagon to fed rats by intraperitoneal injection, or the perfusion of livers from fed rats with glucagon by the method of Mortimore [Mortimore (1963) Am.J. Physiol. 204, 699--704] was associated with increases of 15- and 5-fold respectively, in the time for which a given load of exogenous Ca2+ is retained by mitochondria subsequently isolated from the liver. This effect of glucagon was (a) also induced by N6O2'-dibutyryl cyclic AMP, (b) completely blocked by cycloheximide, (c) relatively slow in onset (15--60 min) and (d) associated with a stimulation of about 20% in the rates of ADP-stimulated oxygen utilization and Ca2+ transport measured in the presence of succinate. 2. Perfusion of livers with glucagon resulted in the isolation of mitochandria which showed a 50% increase, no significant change and a 40% increase in the concentrations of endogenous Ca, Mg and Pi respectively, when compared with mitochondria isolated from control perfused livers. 3. The administration of insulin or adrenaline to fed rats induced increases of 10- and 8-fold respectively, in the time for which Ca2+ is retained by isolated liver mitochondria. Perfusion of livers with insulin had no effect on mitochondrial Ca2+ retention time. 4. The perfusion of livers from starved rats with glucagon, or the administration of either glucagon or insulin to starved rats, increased by about 2.5- and 15-fold respectively, the time for which isolated mitochondria retain Ca2+. 5. Mechanisms which may be responsible for the observed alterations in Ca2+-retention time are discussed."}
{"id": "PMID:215133", "title": "Control of rat skeletal-muscle phosphorylase phosphatase activity by adrenaline.", "content": "Administration of adrenaline to an isolated rat hindlimb preparation rapidly decreased muscle phosphorylase phosphatase (EC 3.1.3.17) activity and increased heat-stable and trypsin-labile phosphatase inhibitor activity. This was associated with increased tissue cyclic AMP concentrations, phosphorylase (EC 2.4.1.1) activation and glycogen synthase (EC 2.4.1.11) inactivation.", "contents": "Control of rat skeletal-muscle phosphorylase phosphatase activity by adrenaline. Administration of adrenaline to an isolated rat hindlimb preparation rapidly decreased muscle phosphorylase phosphatase (EC 3.1.3.17) activity and increased heat-stable and trypsin-labile phosphatase inhibitor activity. This was associated with increased tissue cyclic AMP concentrations, phosphorylase (EC 2.4.1.1) activation and glycogen synthase (EC 2.4.1.11) inactivation."}
{"id": "PMID:215134", "title": "Adenosine 3':5'-cyclic monophosphate production and steroidogenesis by isolated rat adrenal glomerulosa cells. Effects of angiotensin II and [Sar 1,Ala 8]angiotensin II.", "content": "Angiotensin II effects on cyclic AMP production and steroid output were studied in a sensitive preparation of isolated rat adrenal glomerulosa cells. With increasing concentrations of angiotensin II logarithmic dose-response curves for aldosterone and cyclic AMP production were similar. The minimum effective dose (0.2nm) for stimulation of aldosterone production also significantly (P<0.001) increased cyclic AMP output. For both aldosterone and cyclic AMP production, the peptide hormone concentration eliciting maximal response (0.2mum) and the ED(50) (median effective dose) values (1nm) were the same; this is consistent with cyclic AMP acting as an intracellular mediator for angiotensin II-stimulated aldosterone production by glomerulosa cells. The angiotensin II antagonist [Sar(1),Ala(8)]angiotensin II inhibited angiotensin II-stimulated corticosterone and aldosterone production in these cells. An equimolar concentration of antagonist halved the response to 20nm-angiotensin II, and complete inhibition was observed with 0.2mum-antagonist. In contrast, [Sar(1),Ala(8)]angiotensin II had no effect on maximally stimulated steroidogenesis induced by serotonin and a raised extracellular K(+) concentration. Increasing concentrations of [Sar(1),Ala(8)]angiotensin II alone decreased corticosterone and aldosterone outputs significantly (P<0.05) at concentrations of 20nm and 2nm of antagonist respectively. A significant (P<0.001) decrease in cyclic AMP production occurred with 2mum antagonist and this was comparable with the decrease in aldosterone production. It is concluded that [Sar(1),Ala(8)]angiotensin II can independently affect glomerulosa-cell steroidogenesis, possibly by modulating adenylate cyclase activity.", "contents": "Adenosine 3':5'-cyclic monophosphate production and steroidogenesis by isolated rat adrenal glomerulosa cells. Effects of angiotensin II and [Sar 1,Ala 8]angiotensin II. Angiotensin II effects on cyclic AMP production and steroid output were studied in a sensitive preparation of isolated rat adrenal glomerulosa cells. With increasing concentrations of angiotensin II logarithmic dose-response curves for aldosterone and cyclic AMP production were similar. The minimum effective dose (0.2nm) for stimulation of aldosterone production also significantly (P<0.001) increased cyclic AMP output. For both aldosterone and cyclic AMP production, the peptide hormone concentration eliciting maximal response (0.2mum) and the ED(50) (median effective dose) values (1nm) were the same; this is consistent with cyclic AMP acting as an intracellular mediator for angiotensin II-stimulated aldosterone production by glomerulosa cells. The angiotensin II antagonist [Sar(1),Ala(8)]angiotensin II inhibited angiotensin II-stimulated corticosterone and aldosterone production in these cells. An equimolar concentration of antagonist halved the response to 20nm-angiotensin II, and complete inhibition was observed with 0.2mum-antagonist. In contrast, [Sar(1),Ala(8)]angiotensin II had no effect on maximally stimulated steroidogenesis induced by serotonin and a raised extracellular K(+) concentration. Increasing concentrations of [Sar(1),Ala(8)]angiotensin II alone decreased corticosterone and aldosterone outputs significantly (P<0.05) at concentrations of 20nm and 2nm of antagonist respectively. A significant (P<0.001) decrease in cyclic AMP production occurred with 2mum antagonist and this was comparable with the decrease in aldosterone production. It is concluded that [Sar(1),Ala(8)]angiotensin II can independently affect glomerulosa-cell steroidogenesis, possibly by modulating adenylate cyclase activity."}
{"id": "PMID:215135", "title": "Inhibition by calcium ions of adenosine cyclic monophosphate formation in sealed pigeon erythrocyte  'ghosts'. A study using the photoprotein obelin.", "content": "1. Sealed pigeon erythrocyte 'ghosts' were prepared containing ATP and the Ca2+-activated photoprotein obelin to investigate the relationship cyclic AMP formation and internal free Ca2+. 2. The 'ghosts' were characterized by (a) morphology (optical and electron microscopy), (b) composition (haemoglobin, K+, Na+, Mg2+, ATP, obelin), (c) permeability to Ca2+, assessed by obelin luminescence and (d) hormone sensitivity (the effect of beta-adrenergic agonists and antagonists on cyclic AMP formation). 3. The effect of osmolarity at haemolysis and ATP at resealing on these parameters was investigated. 4. Sealed 'ghosts', containing approx. 2% of original haemoglobin, 150mM-K+, 0.5MM-ATP, 10(3)--10(4) obelin luminescence counts/10(6) 'ghosts', which were relatively impermeable to Ca2+ and in which cyclic AMP formation was stimulated by beta-adrenergic agonists over a concentration range similar to that for intact cells, could be prepared after haemolysis in 6mM-NaCl3mM-MgCl2/50mM-Tes, pH7, and resealing for 30min at 37 degrees C in the presence of ATP and 150mM-KCl. 5. The initial rate of adrenaline-stimulated cyclic AMP formation in these 'ghosts' was 30--50% of that in intact cells and was inhibited by the addition of extracellular Ca2+. Addition of Ca2+ to the 'ghosts' resulted in a stimulation of obelin luminescence, indicating an increase in internal free Ca2+ under these conditions. 6. The ionophore A23187 increased the rate of obelin luminescence in the 'ghosts' and also inhibited the adrenaline-stimulated increase in cyclic AMP. 7. The effect of ionophore A23187 on obelin luminescence and on cyclic AMP formation in the 'ghosts' was markedly decreased by sealing EGTA inside the 'ghosts'. 8. It was concluded that cyclic AMP formation inside sealed pigeon erythrocyte 'ghosts' could be inhibited by more than 50% by free Ca2+ concentrations in the range 1--10 micrometer.", "contents": "Inhibition by calcium ions of adenosine cyclic monophosphate formation in sealed pigeon erythrocyte  'ghosts'. A study using the photoprotein obelin. 1. Sealed pigeon erythrocyte 'ghosts' were prepared containing ATP and the Ca2+-activated photoprotein obelin to investigate the relationship cyclic AMP formation and internal free Ca2+. 2. The 'ghosts' were characterized by (a) morphology (optical and electron microscopy), (b) composition (haemoglobin, K+, Na+, Mg2+, ATP, obelin), (c) permeability to Ca2+, assessed by obelin luminescence and (d) hormone sensitivity (the effect of beta-adrenergic agonists and antagonists on cyclic AMP formation). 3. The effect of osmolarity at haemolysis and ATP at resealing on these parameters was investigated. 4. Sealed 'ghosts', containing approx. 2% of original haemoglobin, 150mM-K+, 0.5MM-ATP, 10(3)--10(4) obelin luminescence counts/10(6) 'ghosts', which were relatively impermeable to Ca2+ and in which cyclic AMP formation was stimulated by beta-adrenergic agonists over a concentration range similar to that for intact cells, could be prepared after haemolysis in 6mM-NaCl3mM-MgCl2/50mM-Tes, pH7, and resealing for 30min at 37 degrees C in the presence of ATP and 150mM-KCl. 5. The initial rate of adrenaline-stimulated cyclic AMP formation in these 'ghosts' was 30--50% of that in intact cells and was inhibited by the addition of extracellular Ca2+. Addition of Ca2+ to the 'ghosts' resulted in a stimulation of obelin luminescence, indicating an increase in internal free Ca2+ under these conditions. 6. The ionophore A23187 increased the rate of obelin luminescence in the 'ghosts' and also inhibited the adrenaline-stimulated increase in cyclic AMP. 7. The effect of ionophore A23187 on obelin luminescence and on cyclic AMP formation in the 'ghosts' was markedly decreased by sealing EGTA inside the 'ghosts'. 8. It was concluded that cyclic AMP formation inside sealed pigeon erythrocyte 'ghosts' could be inhibited by more than 50% by free Ca2+ concentrations in the range 1--10 micrometer."}
{"id": "PMID:215136", "title": "Inhibition of adenylate cyclase by adenosine analogues in preparations of broken and intact human platelets. Evidence for the unidirectional control of platelet function by cyclic AMP.", "content": "Whereas adenosine itself exerted independent stimulatory and inhibitory effects on the adenylate cyclase activity of a platelet particulate fraction at low and high concentrations respectively, 2-substituted and N6-monosubstituted adenosines had stimulatory but greatly decreased inhibitory effects. Deoxyadenosines, on the other hand, had enhanced inhibitory but no stimulatory effects. The most potent inhibitors found were, in order of increasing activity, 9-(tetrahydro-2-furyl)adenine (SQ 22536), 2',5'-dideoxyadenosine and 2'-deoxyadenosine 3'-monophosphate. Kinetic studies on prostaglandin E1-activated adenylate cyclase showed that the inhibition caused by either 2',5'-dideoxyadenosine or compound SQ 22536 was non-competitive with MgATP and that the former compound, at least, showed negative co-operativity; 50% inhibition was observed with 4 micron-2',5'-dideoxyadenosine or 13 micron-SQ 22536. These two compounds also inhibited both the basal and prostaglandin E1-activated adenylate cyclase activities of intact platelets, when these were measured as the increases in cyclic [3H]AMP in platelets that had been labelled with [3H]adenine and were then incubated briefly with papaverine or papaverine and prostaglandin E1. Both compounds, but particularly 2',5'-dideoxyadenosine, markedly decreased the inhibition by prostaglandin E1  of platelet aggregation induced by ADP or [arginine]vasopressin as well as the associated increases in platelet cyclic AMP, so providing further evidence that the effects of prostaglandin E1 on platelet aggregation are mediated by cyclic AMP. 2'-Deoxyadenosine 3'-monophosphate did not affect the inhibition of aggregation by prostaglandin E1, suggesting that the site of action of deoxyadenosine derivatives on adenylate cyclase is intracellular. Neither 2',5'-dideoxyadenosine nor compound SQ 22536 alone induced platelet aggregation. Moreover, neither compound potentiated platelet aggregation or the platelet release reaction when suboptimal concentrations of ADP, [arginine]vasopressin, collagen or arachidonate were added to heparinized or citrated platelet-rich plasma in the absence of prostaglandin E1. These results show that cyclic AMP plays no significant role in the responses of platelets to aggregating agents in the absence of compounds that increase the platelet cyclic AMP concentration above the resting value.", "contents": "Inhibition of adenylate cyclase by adenosine analogues in preparations of broken and intact human platelets. Evidence for the unidirectional control of platelet function by cyclic AMP. Whereas adenosine itself exerted independent stimulatory and inhibitory effects on the adenylate cyclase activity of a platelet particulate fraction at low and high concentrations respectively, 2-substituted and N6-monosubstituted adenosines had stimulatory but greatly decreased inhibitory effects. Deoxyadenosines, on the other hand, had enhanced inhibitory but no stimulatory effects. The most potent inhibitors found were, in order of increasing activity, 9-(tetrahydro-2-furyl)adenine (SQ 22536), 2',5'-dideoxyadenosine and 2'-deoxyadenosine 3'-monophosphate. Kinetic studies on prostaglandin E1-activated adenylate cyclase showed that the inhibition caused by either 2',5'-dideoxyadenosine or compound SQ 22536 was non-competitive with MgATP and that the former compound, at least, showed negative co-operativity; 50% inhibition was observed with 4 micron-2',5'-dideoxyadenosine or 13 micron-SQ 22536. These two compounds also inhibited both the basal and prostaglandin E1-activated adenylate cyclase activities of intact platelets, when these were measured as the increases in cyclic [3H]AMP in platelets that had been labelled with [3H]adenine and were then incubated briefly with papaverine or papaverine and prostaglandin E1. Both compounds, but particularly 2',5'-dideoxyadenosine, markedly decreased the inhibition by prostaglandin E1  of platelet aggregation induced by ADP or [arginine]vasopressin as well as the associated increases in platelet cyclic AMP, so providing further evidence that the effects of prostaglandin E1 on platelet aggregation are mediated by cyclic AMP. 2'-Deoxyadenosine 3'-monophosphate did not affect the inhibition of aggregation by prostaglandin E1, suggesting that the site of action of deoxyadenosine derivatives on adenylate cyclase is intracellular. Neither 2',5'-dideoxyadenosine nor compound SQ 22536 alone induced platelet aggregation. Moreover, neither compound potentiated platelet aggregation or the platelet release reaction when suboptimal concentrations of ADP, [arginine]vasopressin, collagen or arachidonate were added to heparinized or citrated platelet-rich plasma in the absence of prostaglandin E1. These results show that cyclic AMP plays no significant role in the responses of platelets to aggregating agents in the absence of compounds that increase the platelet cyclic AMP concentration above the resting value."}
{"id": "PMID:215170", "title": "Effect of intessive plasmapheresis on the plasma cholesterol concentration with familial hypercholesterolemia.", "content": "Plasmapheresis was studied as a means of reducing the serum cholesterol concentration in 3 hypercholesterolemic patients who each underwent courses of intensive plasmapheresis with removal of 250--500 ml of plasma each day for 5--9 days. In one homozygous Type II patient, the serum cholesterol concentration decreased from 609 +/- 45 mg/100 ml (mean +/- SEM) to 365 +/- 17 mg/100 ml (40% decrease, P less than 0.05) with two different courses of plasmapheresis. In the two other patients with non-homozygous hyperbetalipoproteinemia the serum cholesterol concentration decreased from 289 +/- 27 mg/100 ml to 205 +/- 19 mg/100 ml (29% decrease, p less than 0.05). After cessation of treatment, the cholesterol concentration returned to pre-treatment levels in 10--13 days in the homozygous patient and 7 days in one non-homozygous hyperbetalipoproteinemic patient; clofibrate (2 g/day) in this patient was associated with a smaller reduction of the cholesterol concentration with plasmapheresis and an increased rate of return of pre-treatment levels after plasmapheresis was stopped. Sustained plasmapheresis for 6 days in the other non-homozygous hyperbetalipoproteinemic patient resulted in a new approximate \"steady state\" with a serum cholesterol concentration of 176--199 mg/100 ml compared  with a pre-plasmapheresis value of 227 mg/100 ml. The response of the plasma cholesterol levels to plasmapheresis was subjected to kinetic analysis based on a current model of the regulation of lipoprotein metabolism.", "contents": "Effect of intessive plasmapheresis on the plasma cholesterol concentration with familial hypercholesterolemia. Plasmapheresis was studied as a means of reducing the serum cholesterol concentration in 3 hypercholesterolemic patients who each underwent courses of intensive plasmapheresis with removal of 250--500 ml of plasma each day for 5--9 days. In one homozygous Type II patient, the serum cholesterol concentration decreased from 609 +/- 45 mg/100 ml (mean +/- SEM) to 365 +/- 17 mg/100 ml (40% decrease, P less than 0.05) with two different courses of plasmapheresis. In the two other patients with non-homozygous hyperbetalipoproteinemia the serum cholesterol concentration decreased from 289 +/- 27 mg/100 ml to 205 +/- 19 mg/100 ml (29% decrease, p less than 0.05). After cessation of treatment, the cholesterol concentration returned to pre-treatment levels in 10--13 days in the homozygous patient and 7 days in one non-homozygous hyperbetalipoproteinemic patient; clofibrate (2 g/day) in this patient was associated with a smaller reduction of the cholesterol concentration with plasmapheresis and an increased rate of return of pre-treatment levels after plasmapheresis was stopped. Sustained plasmapheresis for 6 days in the other non-homozygous hyperbetalipoproteinemic patient resulted in a new approximate \"steady state\" with a serum cholesterol concentration of 176--199 mg/100 ml compared  with a pre-plasmapheresis value of 227 mg/100 ml. The response of the plasma cholesterol levels to plasmapheresis was subjected to kinetic analysis based on a current model of the regulation of lipoprotein metabolism."}
{"id": "PMID:215171", "title": "Glycosaminoglycan-lipoprotein complexes from aortas of hypercholesterolemic rabbits. Part 1. Isolation and characterization.", "content": "Glycosaminoglycan-lipoprotein complexes were isolated from rabbit aortas exhibiting nearly confluent cholesterol-induced foam cell lesions by extraction with 0.15 M NaCl. Purification and characterization was achieved by gel chromatography, non-ionic differential flotation and by cellulose polyacetate electrophoresis. Analysis showed that these complexes consisted of very low density lipoproteins, heparan sulfate, chondroitin sulfate-C and hyaluronic acid. The demonstration that rabbit intimal foam cell lesions contain  extractable glycosaminoglycan-lipoprotein complexes makes this animal model an excellent tool for further studies on the role of these complexes in the atherogenic process.", "contents": "Glycosaminoglycan-lipoprotein complexes from aortas of hypercholesterolemic rabbits. Part 1. Isolation and characterization. Glycosaminoglycan-lipoprotein complexes were isolated from rabbit aortas exhibiting nearly confluent cholesterol-induced foam cell lesions by extraction with 0.15 M NaCl. Purification and characterization was achieved by gel chromatography, non-ionic differential flotation and by cellulose polyacetate electrophoresis. Analysis showed that these complexes consisted of very low density lipoproteins, heparan sulfate, chondroitin sulfate-C and hyaluronic acid. The demonstration that rabbit intimal foam cell lesions contain  extractable glycosaminoglycan-lipoprotein complexes makes this animal model an excellent tool for further studies on the role of these complexes in the atherogenic process."}
{"id": "PMID:215172", "title": "Efficacy of hypolipidemic treatment in inhibition of experimental atherosclerosis: the effect of nicotinic acid and related compounds.", "content": "The hypolipidemic and antiatherogenic effects of different nicotinic acid derivatives were studied. Five rabbit groups maintained on an atherogenic diet were given simultaneously various nicotinic acid derivatives (50 mg/kg body weight/day): nicotinic acid, Xantinol-nicotinate, beta-pyridylcarbinol or Pirozadil (bis-3,4,5-trimethoxybenzoate, 2,6-pyridindiyldimethylene). All 4 compounds showed a clear hypocholesterolemic and antiatherogenic effect, as measured by serum cholesterol, and by planimetric evaluation of the aortic lesions in terms of percent surface area affected in the aortas and coronary lumen. The simultaneously observed elevation of the HDL/LDL cholesterol ratio of the aortic tissue possibly indicates an antiatherogenic effect of these changes.", "contents": "Efficacy of hypolipidemic treatment in inhibition of experimental atherosclerosis: the effect of nicotinic acid and related compounds. The hypolipidemic and antiatherogenic effects of different nicotinic acid derivatives were studied. Five rabbit groups maintained on an atherogenic diet were given simultaneously various nicotinic acid derivatives (50 mg/kg body weight/day): nicotinic acid, Xantinol-nicotinate, beta-pyridylcarbinol or Pirozadil (bis-3,4,5-trimethoxybenzoate, 2,6-pyridindiyldimethylene). All 4 compounds showed a clear hypocholesterolemic and antiatherogenic effect, as measured by serum cholesterol, and by planimetric evaluation of the aortic lesions in terms of percent surface area affected in the aortas and coronary lumen. The simultaneously observed elevation of the HDL/LDL cholesterol ratio of the aortic tissue possibly indicates an antiatherogenic effect of these changes."}
{"id": "PMID:215173", "title": "Association of structural glycoproteins with lipids or lipoproteins.", "content": "Gradient density ultracentrifugation was used to assess the lipid binding of 125I-labelled structural glycoproteins and standard proteins. The results show that solubilized structural glycoproteins from cartilage or aorta will associate spontaneously with lipids or lipoproteins. In addition, structural glycoprotein preparations from tissues which have not been delipidated contain a fraction which is already associated with lipid. Standard proteins do not behave in the same way. It is proposed that structural glycoprotein-lipid binding may be one of the mechanisms involved in the intercellular deposition of plasma lipoproteins in atherosclerotic arteries.", "contents": "Association of structural glycoproteins with lipids or lipoproteins. Gradient density ultracentrifugation was used to assess the lipid binding of 125I-labelled structural glycoproteins and standard proteins. The results show that solubilized structural glycoproteins from cartilage or aorta will associate spontaneously with lipids or lipoproteins. In addition, structural glycoprotein preparations from tissues which have not been delipidated contain a fraction which is already associated with lipid. Standard proteins do not behave in the same way. It is proposed that structural glycoprotein-lipid binding may be one of the mechanisms involved in the intercellular deposition of plasma lipoproteins in atherosclerotic arteries."}
{"id": "PMID:215174", "title": "Dose-response study of bezafibrate on serum lipoprotein concentrations in hyperlipoproteinanemia.", "content": "The effect of bezafibrate in the dosages 450, 900 and 1350 mg daily on serum lipoprotein concentrations were studied in 20 subjects with primary hyperlipoproteinaemia (16 of type IV, 2 of type II B, 1 of type III). Except for LDL cholesterol maximum effects were obtained with 450 mg daily. Total serum cholesterol and triglycerides (TG) fell significantly. Mean very low density lipoprotein (VLDL) TG fell by 54%. The maximum effect on low density lipoprotein was obtained with 900 mg daily. The effect was highly dependent on initial concentrations, decreases being observed above 4 mmoles/l and increases below that concentration. High density lipoprotein cholesterol increased by 31% (P less than 0.01) independently of the VLDL decrease. Three subjects suffered gastrointestinal side-effects on 1350 mg daily. Only benign reversible changes were noted on non-lipid measurements. Bezafibrate is a well-tolerated drug with a good VLDL TG lowering effect. It is particularly effective in increasing HDL cholesterol concentrations.", "contents": "Dose-response study of bezafibrate on serum lipoprotein concentrations in hyperlipoproteinanemia. The effect of bezafibrate in the dosages 450, 900 and 1350 mg daily on serum lipoprotein concentrations were studied in 20 subjects with primary hyperlipoproteinaemia (16 of type IV, 2 of type II B, 1 of type III). Except for LDL cholesterol maximum effects were obtained with 450 mg daily. Total serum cholesterol and triglycerides (TG) fell significantly. Mean very low density lipoprotein (VLDL) TG fell by 54%. The maximum effect on low density lipoprotein was obtained with 900 mg daily. The effect was highly dependent on initial concentrations, decreases being observed above 4 mmoles/l and increases below that concentration. High density lipoprotein cholesterol increased by 31% (P less than 0.01) independently of the VLDL decrease. Three subjects suffered gastrointestinal side-effects on 1350 mg daily. Only benign reversible changes were noted on non-lipid measurements. Bezafibrate is a well-tolerated drug with a good VLDL TG lowering effect. It is particularly effective in increasing HDL cholesterol concentrations."}
{"id": "PMID:215175", "title": "One-year study of the effect of bezafibrate on serum lipoprotein concentrations in hyperlipoproteinaemia.", "content": "The effect of bezafibrate (2-(4-[2-(4-chlorobenzamido)-ethyl]-phenoxy)-2-methylporopionic acid) (450 mg daily) on serum lipoprotein concentrations was studied for 1 year in 14 subjects with hyperlipoproteinaemia (3 of type II A, 2 of type II B, 2 of type III and 7 of type IV). After 2 months serum cholesterol decreased from 7.12--6.08 mmoles/l (15% P less than 0.01), triglycerides from 2.52--1.96 mmoles/l (22%, P less than 0.01), very low density lipoprotein triglycerides from 1.48--0.86 mmoles/l (42%, P less than 0.01) and low density lipoprotein cholesterol from 5.00--3.81 mmoles/l (24%, P less than 0.01). While triglyceride concentrations of serum and lipoproteins remained constant for 1 year, serum and LDL cholesterol concentrations increased slightly after 6 and 12 months. The former rise was partly due also to a rise of the possibly beneficial high density lipoprotein cholesterol from 1.27--1.68 mmoles/l (32%, P less than 0.01) after 6 months, making the effect on total cholesterol less pronounced. Subjective side-effects were nausea in one patient. No severe biochemical side-effects were noted.", "contents": "One-year study of the effect of bezafibrate on serum lipoprotein concentrations in hyperlipoproteinaemia. The effect of bezafibrate (2-(4-[2-(4-chlorobenzamido)-ethyl]-phenoxy)-2-methylporopionic acid) (450 mg daily) on serum lipoprotein concentrations was studied for 1 year in 14 subjects with hyperlipoproteinaemia (3 of type II A, 2 of type II B, 2 of type III and 7 of type IV). After 2 months serum cholesterol decreased from 7.12--6.08 mmoles/l (15% P less than 0.01), triglycerides from 2.52--1.96 mmoles/l (22%, P less than 0.01), very low density lipoprotein triglycerides from 1.48--0.86 mmoles/l (42%, P less than 0.01) and low density lipoprotein cholesterol from 5.00--3.81 mmoles/l (24%, P less than 0.01). While triglyceride concentrations of serum and lipoproteins remained constant for 1 year, serum and LDL cholesterol concentrations increased slightly after 6 and 12 months. The former rise was partly due also to a rise of the possibly beneficial high density lipoprotein cholesterol from 1.27--1.68 mmoles/l (32%, P less than 0.01) after 6 months, making the effect on total cholesterol less pronounced. Subjective side-effects were nausea in one patient. No severe biochemical side-effects were noted."}
{"id": "PMID:215176", "title": "The action of human high density lipoprotein on cholesterol crystals. Part 1. Light-microscopic observations.", "content": "High density lipoprotein (HDL) was found in vitro to form myelin buds (liposomes) from washed crystals of free cholesterol (commercial or atheroma sources). This activity led to the progressive destruction and solubilization of the crystals. Low density and very low density lipoproteins did not have any effect. Liposome formation and solubilization were accelerated by calcium ions, phospholipase A and polyunsaturated lecithin (Lipostabil). Cholesterol crystals were nearly completely destroyed after 18 h incubation with HDL-Lipostabil.", "contents": "The action of human high density lipoprotein on cholesterol crystals. Part 1. Light-microscopic observations. High density lipoprotein (HDL) was found in vitro to form myelin buds (liposomes) from washed crystals of free cholesterol (commercial or atheroma sources). This activity led to the progressive destruction and solubilization of the crystals. Low density and very low density lipoproteins did not have any effect. Liposome formation and solubilization were accelerated by calcium ions, phospholipase A and polyunsaturated lecithin (Lipostabil). Cholesterol crystals were nearly completely destroyed after 18 h incubation with HDL-Lipostabil."}
{"id": "PMID:215177", "title": "The action of human high density lipoprotein on cholesterol crystals. Part 2. Biochemical observations.", "content": "Electron microscopy of the reaction product between human pooled high density lipoprotein (HDL) and cholesterol shows that characteristic liposome macromicellar bodies are formed. These bodies vary in size between 30 and 1200 nm. In comparison with HDL, they contain markedly more cholesterol, but less protein and phospholipid. Their phospholipid pattern shows enrichment with sphingomyelin and phosphatidyl serine in comparison with HDL.", "contents": "The action of human high density lipoprotein on cholesterol crystals. Part 2. Biochemical observations. Electron microscopy of the reaction product between human pooled high density lipoprotein (HDL) and cholesterol shows that characteristic liposome macromicellar bodies are formed. These bodies vary in size between 30 and 1200 nm. In comparison with HDL, they contain markedly more cholesterol, but less protein and phospholipid. Their phospholipid pattern shows enrichment with sphingomyelin and phosphatidyl serine in comparison with HDL."}
{"id": "PMID:215179", "title": "Potentiation of isoprenaline-induced plasma cyclic AMP response by aminophylline in normal and asthmatic subjects.", "content": "1 The effect of intravenous aminophylline infusion (6 mg-1 kg in 20 min, then 0.9 mg-1 kg-1 h thereafter) and its interaction with inhaled isoprenaline (800 microgram ex inhaler) on plasma cyclic AMP levels was studied in five normal and five asthmatic subjects. 2 Aminophylline infusion alone did not significantly change plasma cyclic AMP levels in either group. 3 In both groups, the plasma cyclic AMP response to isoprenaline aerosol inhalation was enhanced by aminophylline, although to a lesser degree in the asthmatic subjects. 4 The results provide in vivo evidence consistent with the hypothesis that in man, therapeutic doses of aminophylline may exert their clinical effects by inhibition of cyclic AMP phosphodiesterase.", "contents": "Potentiation of isoprenaline-induced plasma cyclic AMP response by aminophylline in normal and asthmatic subjects. 1 The effect of intravenous aminophylline infusion (6 mg-1 kg in 20 min, then 0.9 mg-1 kg-1 h thereafter) and its interaction with inhaled isoprenaline (800 microgram ex inhaler) on plasma cyclic AMP levels was studied in five normal and five asthmatic subjects. 2 Aminophylline infusion alone did not significantly change plasma cyclic AMP levels in either group. 3 In both groups, the plasma cyclic AMP response to isoprenaline aerosol inhalation was enhanced by aminophylline, although to a lesser degree in the asthmatic subjects. 4 The results provide in vivo evidence consistent with the hypothesis that in man, therapeutic doses of aminophylline may exert their clinical effects by inhibition of cyclic AMP phosphodiesterase."}
{"id": "PMID:215180", "title": "Chemical modification and immunogenicity of membrane fractions from mouse tumour cells.", "content": "A crude membrane fraction isolated from mouse tumour cells was treated with various chemicals. The effects on the immunogenicity of the membrane sample were tested in syngeneic mice for tumour protection, using a challenge dose of 10(5) viable tumour cells. Best protection was obtained after immunization of mice with a membrane sample modified with dimethylsulphate. Up to 60% of the animals remained tumour free, and the tumour-bearing animals showed a greatly increased mean survival time. The post-challenge sera contained no detectable amounts of cytotoxic antibodies. The membrane sample isolated from tumour cells which had been modified with dimethylsulphate showed less immunogenicity than the modified cells or the membrane fraction from unmodified cells.", "contents": "Chemical modification and immunogenicity of membrane fractions from mouse tumour cells. A crude membrane fraction isolated from mouse tumour cells was treated with various chemicals. The effects on the immunogenicity of the membrane sample were tested in syngeneic mice for tumour protection, using a challenge dose of 10(5) viable tumour cells. Best protection was obtained after immunization of mice with a membrane sample modified with dimethylsulphate. Up to 60% of the animals remained tumour free, and the tumour-bearing animals showed a greatly increased mean survival time. The post-challenge sera contained no detectable amounts of cytotoxic antibodies. The membrane sample isolated from tumour cells which had been modified with dimethylsulphate showed less immunogenicity than the modified cells or the membrane fraction from unmodified cells."}
{"id": "PMID:215181", "title": "ESR study of development of RFM/Un murine myeloid leukaemia.", "content": "The blood, spleen and liver of RFM/Un mice were examined by means of electron spin resonance (ESR) throughout the course of myeloid leukaemia induced by i.v. injection of leukaemic spleen cells. Marked changes in the concentration of iron transferrin and caeruloplasmin were observed in the blood 1 day after injection. As the disease progressed, changes occurred in the concentrations of the ascorbyl radical and of paramagnetic metal complexes in both spleen and liver. These changes are compared with those induced in RF/J mice injected with normal and leukaemic spleen cells from RFM/Un mice.", "contents": "ESR study of development of RFM/Un murine myeloid leukaemia. The blood, spleen and liver of RFM/Un mice were examined by means of electron spin resonance (ESR) throughout the course of myeloid leukaemia induced by i.v. injection of leukaemic spleen cells. Marked changes in the concentration of iron transferrin and caeruloplasmin were observed in the blood 1 day after injection. As the disease progressed, changes occurred in the concentrations of the ascorbyl radical and of paramagnetic metal complexes in both spleen and liver. These changes are compared with those induced in RF/J mice injected with normal and leukaemic spleen cells from RFM/Un mice."}
{"id": "PMID:215182", "title": "Paramagnetic changes in cancer: growth of Walker 256 carcinoma studied in frozen and lyophilized tissues.", "content": "Samples of Walker 256 carcinoma grown in muscles of Sprague-Dawley rats were studied at low temperatures before and after lyophilization. The effects of lyophilization on the ESR spectra were different for tumours and normal muscle. Prior to lyophilization of a tumour sample, there was a decrease in free radicals, while after the lyophilization, there was an \"increase\". The \"increase\" was due to the lyophilized tumour having a narrower line, producing a greater peak-peak height measurement than in muscle, without an increase in the total number of spins. Exposure of lyophilized samples to air produced an increase in the intensity of the spectra and a change in line shape; also these effects differed for tumour and muscle. Mn++ levels were lower in tumour than in muscle, a difference eliminated by lyophilization. Poor growth conditions in tumours increased the occurrence of ESR spectra due to NO complexes with both heme and non-heme iron proteins. These results may help to resolve the principal controversies about experimental findings in ESR of tumours. At least part of the signals seen after lyophilization do not reflect free radicals in vivo. The signals after lyophilization reflect biochemical differences between tumour and muscle; spectroscopic data indicate that it is feasible to determine the molecular basis of these differences.", "contents": "Paramagnetic changes in cancer: growth of Walker 256 carcinoma studied in frozen and lyophilized tissues. Samples of Walker 256 carcinoma grown in muscles of Sprague-Dawley rats were studied at low temperatures before and after lyophilization. The effects of lyophilization on the ESR spectra were different for tumours and normal muscle. Prior to lyophilization of a tumour sample, there was a decrease in free radicals, while after the lyophilization, there was an \"increase\". The \"increase\" was due to the lyophilized tumour having a narrower line, producing a greater peak-peak height measurement than in muscle, without an increase in the total number of spins. Exposure of lyophilized samples to air produced an increase in the intensity of the spectra and a change in line shape; also these effects differed for tumour and muscle. Mn++ levels were lower in tumour than in muscle, a difference eliminated by lyophilization. Poor growth conditions in tumours increased the occurrence of ESR spectra due to NO complexes with both heme and non-heme iron proteins. These results may help to resolve the principal controversies about experimental findings in ESR of tumours. At least part of the signals seen after lyophilization do not reflect free radicals in vivo. The signals after lyophilization reflect biochemical differences between tumour and muscle; spectroscopic data indicate that it is feasible to determine the molecular basis of these differences."}
{"id": "PMID:215183", "title": "C-type virus particles in human urogenital tumours after heterotransplantation into nude mice.", "content": "C-type viruses were formed in heterotransplants of 5/14 human urogenital tumours which had been serially transferred in nude mice of NIH(S) background. Except for one case in which C-type particles were present in the epithelial cells as well as the connective tissue, the viruses were only found within the stroma of the heterotransplanted tumours. Peroxidase labelling with anti-mouse serum demonstrated that the connective tissue supporting the transplanted human tumours was of mouse origin. Competition radioimmunoassays demonstrated that MuLV interspecies viral protein was present in high titre in the transplanted tumour extracts and also in extracts of 2 spontaneous mouse-tumour extracts. These data suggest that endogenous viruses of the nude mice are activated by the graft, and only subsequently infect the human tumour cells and form particles.", "contents": "C-type virus particles in human urogenital tumours after heterotransplantation into nude mice. C-type viruses were formed in heterotransplants of 5/14 human urogenital tumours which had been serially transferred in nude mice of NIH(S) background. Except for one case in which C-type particles were present in the epithelial cells as well as the connective tissue, the viruses were only found within the stroma of the heterotransplanted tumours. Peroxidase labelling with anti-mouse serum demonstrated that the connective tissue supporting the transplanted human tumours was of mouse origin. Competition radioimmunoassays demonstrated that MuLV interspecies viral protein was present in high titre in the transplanted tumour extracts and also in extracts of 2 spontaneous mouse-tumour extracts. These data suggest that endogenous viruses of the nude mice are activated by the graft, and only subsequently infect the human tumour cells and form particles."}
{"id": "PMID:215184", "title": "ACTH-like activity in immune complexes of patients with oat-cell carcinoma of the lung.", "content": "Immune complexes could be isolated from sera of 7 patients with oat-cell carcinoma of the lung, but not from 5 normal controls, using zonal ultracentrifugation. After ultracentrifugation, fractions containing macromolecular IgG were absorbed on a protein A-sepharose column and the immune complexes were eluted and dissociated by glycin-HCl buffer at pH 3.5. The eluates were tested for the presence of tumour-associated proteins as carcinoembryonic antigen (CEA), non-specific crossreacting antigen (NCA), alpha2 pregnancy associated antigen (alpha2PAG) and isoferritin. Whereas none of these tumour-associated antigens could be demonstrated, an ACTH-like activity was detected in the immune-complex fractions of 4 patients with oat-cell carcinoma, by radioimmuno- and bioassay. Polyacrylamide electrophoresis of an immune-complex fraction from a patient with Cushing syndrome showed ACTH-like activities, with mol. wt of 110,000, 75,000, 30,000 and less than 20,000 (all glycoproteins) indicating the presence of different subfractions of big ACTH.", "contents": "ACTH-like activity in immune complexes of patients with oat-cell carcinoma of the lung. Immune complexes could be isolated from sera of 7 patients with oat-cell carcinoma of the lung, but not from 5 normal controls, using zonal ultracentrifugation. After ultracentrifugation, fractions containing macromolecular IgG were absorbed on a protein A-sepharose column and the immune complexes were eluted and dissociated by glycin-HCl buffer at pH 3.5. The eluates were tested for the presence of tumour-associated proteins as carcinoembryonic antigen (CEA), non-specific crossreacting antigen (NCA), alpha2 pregnancy associated antigen (alpha2PAG) and isoferritin. Whereas none of these tumour-associated antigens could be demonstrated, an ACTH-like activity was detected in the immune-complex fractions of 4 patients with oat-cell carcinoma, by radioimmuno- and bioassay. Polyacrylamide electrophoresis of an immune-complex fraction from a patient with Cushing syndrome showed ACTH-like activities, with mol. wt of 110,000, 75,000, 30,000 and less than 20,000 (all glycoproteins) indicating the presence of different subfractions of big ACTH."}
{"id": "PMID:215185", "title": "Significance of the proline assay in the study of anti-MSV cell-mediated immune reactions.", "content": "The cytolysis of 3H-proline-labelled tumour cells growing in monolayer by syngeneic immune lymphocytes has been studied in the murine sarcoma virus (MSV) system. Results show that the proline assay (PA) is a convenient way to reveal the activity of cytolytic T lymphocytes against FMR-like antigens. Using the same effector and target cells, the classical chromium-release test (CRT) fails to reveal any cytolytic activity, and the visual microcytotoxicity assay as well as several derived isotopic methods are known to reveal mainly non-specific reactions due to non-T effector cells. The PA, therefore, appears to be a useful method for testing an antitumour reaction against tumour cells in monolayer. The results are, however, different from those obtained in the CRT using the same effector cells but lymphoma cells in suspension as targets, the major discrepancies being the following: (a) the PA does not provide truly quantitative data, due to the very high lymphoid: effector cell ratios needed in this test; (b) unexpected patterns of antigenic specificities are sometimes detected in PA; (c) a non-specific natural killer activity of non-T cells is frequently detected in the PA, masking at low lymphoid: target cell ratios the T-dependent specific cytolysis; (d) the H-2 restriction of the cytolytic T-cell activity is poorly detected in PA, whereas the role of H-2 antigens is clearly shown by blocking experiments using anti-H-2 antibodies.", "contents": "Significance of the proline assay in the study of anti-MSV cell-mediated immune reactions. The cytolysis of 3H-proline-labelled tumour cells growing in monolayer by syngeneic immune lymphocytes has been studied in the murine sarcoma virus (MSV) system. Results show that the proline assay (PA) is a convenient way to reveal the activity of cytolytic T lymphocytes against FMR-like antigens. Using the same effector and target cells, the classical chromium-release test (CRT) fails to reveal any cytolytic activity, and the visual microcytotoxicity assay as well as several derived isotopic methods are known to reveal mainly non-specific reactions due to non-T effector cells. The PA, therefore, appears to be a useful method for testing an antitumour reaction against tumour cells in monolayer. The results are, however, different from those obtained in the CRT using the same effector cells but lymphoma cells in suspension as targets, the major discrepancies being the following: (a) the PA does not provide truly quantitative data, due to the very high lymphoid: effector cell ratios needed in this test; (b) unexpected patterns of antigenic specificities are sometimes detected in PA; (c) a non-specific natural killer activity of non-T cells is frequently detected in the PA, masking at low lymphoid: target cell ratios the T-dependent specific cytolysis; (d) the H-2 restriction of the cytolytic T-cell activity is poorly detected in PA, whereas the role of H-2 antigens is clearly shown by blocking experiments using anti-H-2 antibodies."}
{"id": "PMID:215188", "title": "Malate dehydrogenase. Kinetic studies of substrate activation of supernatant enzyme by L-malate.", "content": "At pH 8.0 in 0.05 M Tris-acetate buffer at 25 degrees C, homogeneous supernatant malate dehydrogenase exhibits substrate activation by L-malate. The turnover number, Michaelis constant for L-malate, and Michaelis constant for NAD are: 0.46 X 10(4) min(-1), 0.036 mM, and 0.14 mM, respectively, for nonactivated enzyme and 1.1 X 10(4) min(-1), 0.2mM, and 0.047 mM for the same series of constants in activated enzyme. Nonactivating behavior is observed at concentrations between 0.02 and 0.15 mM L-malate and activating behavior is observed between 0.15 and 0.5 mM L-malate. L-Malate activation is compared with similar activation of mitochondrial malate dehydrogenase. While it is not possible to exclude unequivocally all mechanisms, the data seem to be consistent with the occurrence of a fundamentally ordered bi bi mechanism, possibly involving activation through the allosteric binding of L-malate. It is concluded that the data are consistent with a form of the \"reciprocating compulsory order mechanism\" in which nonactivated enzyme reflects catalysis by one subunit and activated catalysis expresses the coordinated activity of two subunits. The allosteric interaction and the \"reciprocating mechanism/ are not mutually exclusive.", "contents": "Malate dehydrogenase. Kinetic studies of substrate activation of supernatant enzyme by L-malate. At pH 8.0 in 0.05 M Tris-acetate buffer at 25 degrees C, homogeneous supernatant malate dehydrogenase exhibits substrate activation by L-malate. The turnover number, Michaelis constant for L-malate, and Michaelis constant for NAD are: 0.46 X 10(4) min(-1), 0.036 mM, and 0.14 mM, respectively, for nonactivated enzyme and 1.1 X 10(4) min(-1), 0.2mM, and 0.047 mM for the same series of constants in activated enzyme. Nonactivating behavior is observed at concentrations between 0.02 and 0.15 mM L-malate and activating behavior is observed between 0.15 and 0.5 mM L-malate. L-Malate activation is compared with similar activation of mitochondrial malate dehydrogenase. While it is not possible to exclude unequivocally all mechanisms, the data seem to be consistent with the occurrence of a fundamentally ordered bi bi mechanism, possibly involving activation through the allosteric binding of L-malate. It is concluded that the data are consistent with a form of the \"reciprocating compulsory order mechanism\" in which nonactivated enzyme reflects catalysis by one subunit and activated catalysis expresses the coordinated activity of two subunits. The allosteric interaction and the \"reciprocating mechanism/ are not mutually exclusive."}
{"id": "PMID:215189", "title": "Combined coenzyme-substrate analogues of various dehydrogenases. Synthesis of (3S)- and (3R)-5-(3-carboxy-3-hydroxypropyl)nicotinamide adenine dinucleotide and their interaction with (S)- and (R)-lactate-specific dehydrogenases.", "content": "Two diastereomeric nicotinamide adenine dinucleotide (NAD+) derivatives were synthesized in which the substrates of (S)-and (R)-lactate-specific dehydrogenases are covalently attached via a methylene spacer at position 5 of the nicotinamide ring. The corresponding nicotinamide derivatives were obtained stereospecifically by enzymatic reduction of 5-(2-oxalylethyl)nicotinamide. (3S)-5-(3-Carboxy-3-hydroxypropyl)-NAD+ undergoes and intramolecular hydride transfer in the presence of pig heart lactate dehydrogenase, forming the corresponding coenzyme-substrate analogue composed of pyruvate and NADH. No cross-reaction products resulting from an intermolecular reaction are observed. Two (R)-lactate specific dehydrogenases, however, do not catalyze a similar reaction in either one of the two diastereomers. A possible arrangement of the substrates in the active centers of these enzymes is proposed. 5-Methyl-NAD+ and 5-methyl-NADH are active coenzymes of pig heart lactate dehydrogenase in contrast to reports in the literature. (S)-Lactate binds to this enzyme in the absence of coenzyme, exhibiting a dissociation constant of 11 mM.", "contents": "Combined coenzyme-substrate analogues of various dehydrogenases. Synthesis of (3S)- and (3R)-5-(3-carboxy-3-hydroxypropyl)nicotinamide adenine dinucleotide and their interaction with (S)- and (R)-lactate-specific dehydrogenases. Two diastereomeric nicotinamide adenine dinucleotide (NAD+) derivatives were synthesized in which the substrates of (S)-and (R)-lactate-specific dehydrogenases are covalently attached via a methylene spacer at position 5 of the nicotinamide ring. The corresponding nicotinamide derivatives were obtained stereospecifically by enzymatic reduction of 5-(2-oxalylethyl)nicotinamide. (3S)-5-(3-Carboxy-3-hydroxypropyl)-NAD+ undergoes and intramolecular hydride transfer in the presence of pig heart lactate dehydrogenase, forming the corresponding coenzyme-substrate analogue composed of pyruvate and NADH. No cross-reaction products resulting from an intermolecular reaction are observed. Two (R)-lactate specific dehydrogenases, however, do not catalyze a similar reaction in either one of the two diastereomers. A possible arrangement of the substrates in the active centers of these enzymes is proposed. 5-Methyl-NAD+ and 5-methyl-NADH are active coenzymes of pig heart lactate dehydrogenase in contrast to reports in the literature. (S)-Lactate binds to this enzyme in the absence of coenzyme, exhibiting a dissociation constant of 11 mM."}
{"id": "PMID:215191", "title": "Surface-specific iodination of membrane proteins of viruses and eucaryotic cells using 1,3,4,6-tetrachloro-3alpha,6alpha-diphenylglycoluril.", "content": "The use of the iodinating reagent 1,3,4,6-tetrachloro-3alpha,6alpha-diphenylglycouril (chloroglycoluril) to selectively label membrane surface proteins was investigated with the following systems: enveloped viruses (Sendai and Newcastle disease viruses), human erythrocytes, and nucleated cells propagated both in suspension (EL-4) and in monolayer culture (BHK-21). Conditions are described for specifically iodinating surface proteins while maintaining full virus integrity or cell viability. Comparison of the chloroglycoluril method with the lactoperoxidase and chloramine-T methods for labeling surface membrane proteins shows that the chloroglycoluril method has a number of advantages: It routinely produces a 3- to 17-fold greater specific radioactivity without sacrificing viral or cellular integrity, it is technically simpler to use, it does not require the addition of extraneous protein to initiate the reaction nor a strong reducing reagent to terminate it. Chloroglycoluril also proved to be an effective substitute for chloramine-T in the nonvectorial labeling of viral and cellular proteins. Membrane protein samples were solubilized with the detergent sodium dodecyl sulfate before iodination or labeled in the presence of high iodide concentrations without prior solubilization. The resulting specific radioactivities generated by the use of chloroglycoluril were equal to or greater than those generated by the chloramine-T method. The effectiveness, simplicity of use, and versatility of chloroglycoluril recommend it as an iodinating reagent for both surface-specific and nonvectorial labeling of membrane systems.", "contents": "Surface-specific iodination of membrane proteins of viruses and eucaryotic cells using 1,3,4,6-tetrachloro-3alpha,6alpha-diphenylglycoluril. The use of the iodinating reagent 1,3,4,6-tetrachloro-3alpha,6alpha-diphenylglycouril (chloroglycoluril) to selectively label membrane surface proteins was investigated with the following systems: enveloped viruses (Sendai and Newcastle disease viruses), human erythrocytes, and nucleated cells propagated both in suspension (EL-4) and in monolayer culture (BHK-21). Conditions are described for specifically iodinating surface proteins while maintaining full virus integrity or cell viability. Comparison of the chloroglycoluril method with the lactoperoxidase and chloramine-T methods for labeling surface membrane proteins shows that the chloroglycoluril method has a number of advantages: It routinely produces a 3- to 17-fold greater specific radioactivity without sacrificing viral or cellular integrity, it is technically simpler to use, it does not require the addition of extraneous protein to initiate the reaction nor a strong reducing reagent to terminate it. Chloroglycoluril also proved to be an effective substitute for chloramine-T in the nonvectorial labeling of viral and cellular proteins. Membrane protein samples were solubilized with the detergent sodium dodecyl sulfate before iodination or labeled in the presence of high iodide concentrations without prior solubilization. The resulting specific radioactivities generated by the use of chloroglycoluril were equal to or greater than those generated by the chloramine-T method. The effectiveness, simplicity of use, and versatility of chloroglycoluril recommend it as an iodinating reagent for both surface-specific and nonvectorial labeling of membrane systems."}
{"id": "PMID:215193", "title": "Translation of chick calvarial procollagen messenger RNA'S by a messenger RNA dependent reticulocyte lysate.", "content": "A method was developed for the extraction of RNA from chick embryo calvaria which should be generally applicable to other connective tissues. Total RNA prepared by this method was translated by a mRNA-dependent reticulocyte lysate into discrete pro alpha chains. Several criteria were used to identify these translation products, including (1) preferential labeling with [3H]proline, (2) appropriate migration on sodium dodecyl sulfate-polyacrylamide gels, (3) selective sensitivity to collagenase digestion, and (4) specific precipitability by two different antisera against procollagen. Data from the immunoprecipitation experiments indicated that the majority of the pro alpha chains contained the carboxy-terminal antigenic determinants. These results demonstrate that this translation system can be used as an assay for intact procollagen mRNAs and as a source of in vitro synthesized pro alpha chains for future structural analysis.", "contents": "Translation of chick calvarial procollagen messenger RNA'S by a messenger RNA dependent reticulocyte lysate. A method was developed for the extraction of RNA from chick embryo calvaria which should be generally applicable to other connective tissues. Total RNA prepared by this method was translated by a mRNA-dependent reticulocyte lysate into discrete pro alpha chains. Several criteria were used to identify these translation products, including (1) preferential labeling with [3H]proline, (2) appropriate migration on sodium dodecyl sulfate-polyacrylamide gels, (3) selective sensitivity to collagenase digestion, and (4) specific precipitability by two different antisera against procollagen. Data from the immunoprecipitation experiments indicated that the majority of the pro alpha chains contained the carboxy-terminal antigenic determinants. These results demonstrate that this translation system can be used as an assay for intact procollagen mRNAs and as a source of in vitro synthesized pro alpha chains for future structural analysis."}
{"id": "PMID:215195", "title": "Subunit dissociation in the allosteric regulation of glycerol kinase from Escherichia coli. 2. Physical evidence.", "content": "The dependence of the molecular weight of glycerol kinase on enzyme concentration and on binding of fructose 1,6-bisphosphate has been examined by velocity sedimentation, gel filtration, and polyacrylamide gel electrophoresis. The sedimentation coefficient and Stokes radius decrease as a consequence of dilution in a manner consistent with dissociation into half-molecules, with limiting values suggesting molecular weights of about 218,000 and 136,000 for the associated and dissociated species, respectively. Fructose 1,6-bisphosphate (5 mM) prevents the decrease in sedimentation coefficient brought about by dilution, suggesting a decrease in the apparent subunit dissociation constant of at least four orders of magnitude. Electrophoretic mobility in polyacrylamide gels increases as a consequence of dilution in the absence, but not in the presence, of fructose 1,6-bisphosphate. Ferguson plots indicate that glycerol kinase has the same molecular weight in the presence of fructose 1,6-bisphosphate as the covalently cross-linked tetramer and is substantially smaller in the absence of fructose 1,6-bisphosphate. These results are consistent with the model of glycerol kinase proposed in the preceding paper of this issue [de Riel, J.K., and Paulus, H. (1978), Biochemistry 17] relating subunit dissociation and ligand binding.", "contents": "Subunit dissociation in the allosteric regulation of glycerol kinase from Escherichia coli. 2. Physical evidence. The dependence of the molecular weight of glycerol kinase on enzyme concentration and on binding of fructose 1,6-bisphosphate has been examined by velocity sedimentation, gel filtration, and polyacrylamide gel electrophoresis. The sedimentation coefficient and Stokes radius decrease as a consequence of dilution in a manner consistent with dissociation into half-molecules, with limiting values suggesting molecular weights of about 218,000 and 136,000 for the associated and dissociated species, respectively. Fructose 1,6-bisphosphate (5 mM) prevents the decrease in sedimentation coefficient brought about by dilution, suggesting a decrease in the apparent subunit dissociation constant of at least four orders of magnitude. Electrophoretic mobility in polyacrylamide gels increases as a consequence of dilution in the absence, but not in the presence, of fructose 1,6-bisphosphate. Ferguson plots indicate that glycerol kinase has the same molecular weight in the presence of fructose 1,6-bisphosphate as the covalently cross-linked tetramer and is substantially smaller in the absence of fructose 1,6-bisphosphate. These results are consistent with the model of glycerol kinase proposed in the preceding paper of this issue [de Riel, J.K., and Paulus, H. (1978), Biochemistry 17] relating subunit dissociation and ligand binding."}
{"id": "PMID:215197", "title": "Nicotinamide adenine dinucleotide dependent isocitrate dehydrogenase from beef heart: subunit heterogeneity and enzyme dissociation.", "content": "Heterogeneity in the subunits of nicotinamide adenine dinucleotide dependent isocitrate dehydrogenase from beef heart mitochondria was investigated using one- and two-dimensional electrophoretic analyses in polyacrylamide gels. Electrophoresis under nondenaturing conditions, at several values of pH and gel concentration, followed by second-dimension electrophoresis in the presence of sodium dodecyl sulfate showed that the active enzyme contains four different subunits. The details of these two-dimensional patterns, reelectrophoresis of the active enzyme band under nondenaturing conditions, together with additional evidence indicate that under certain nondenaturing conditions the enzyme exists partially dissociated into its subunits. The molecular weights of the four subunits, determined from electrophoretic mobilities obtained in the presence of sodium dodecyl sulfate, were different, varying between 39 000 and 41 300. Tryptic peptide maps of the subunits are substantially different.", "contents": "Nicotinamide adenine dinucleotide dependent isocitrate dehydrogenase from beef heart: subunit heterogeneity and enzyme dissociation. Heterogeneity in the subunits of nicotinamide adenine dinucleotide dependent isocitrate dehydrogenase from beef heart mitochondria was investigated using one- and two-dimensional electrophoretic analyses in polyacrylamide gels. Electrophoresis under nondenaturing conditions, at several values of pH and gel concentration, followed by second-dimension electrophoresis in the presence of sodium dodecyl sulfate showed that the active enzyme contains four different subunits. The details of these two-dimensional patterns, reelectrophoresis of the active enzyme band under nondenaturing conditions, together with additional evidence indicate that under certain nondenaturing conditions the enzyme exists partially dissociated into its subunits. The molecular weights of the four subunits, determined from electrophoretic mobilities obtained in the presence of sodium dodecyl sulfate, were different, varying between 39 000 and 41 300. Tryptic peptide maps of the subunits are substantially different."}
{"id": "PMID:215200", "title": "Generation of a free alpha-amino group by Raney nickel after 2-nitro-5-thiocyanobenzoic acid cleavage at cysteine residues: application to automated sequencing.", "content": "The selective reaction of SH containing proteins and peptides with NTCB (2-nitro-5-thiocyanobenzoic acid) has been reported (Degani, Y., & Patchornick, A. (1974) Biochemistry 13, 1; Jacobson, G.A., Schaffer, M.H., Stark, G.R., & Vanaman, T.C. (1973) J. Biol. Chem. 248, 6583). With this reagent, cysteinyl peptide bonds are selectively cyanylated and subsequently cleaved under alkaline conditions. In the present study we have successfully cleaved the beta-chains of guinea pig hemoglobin at the single cysteine and the peptides thus obtained were separated. However, the C-terminal peptide was blocked at its N terminal by a thiazolidine ring and hence could not be used for Edman degradation sequence analysis. Deblocking of this peptide was successfully done by Raney nickel in the buffer medium of pH 7.0, and also in water, at 50 degrees C for 6 to 10 h. The Raney nickel reagent is used in large excess by weight (at least ten times the weight of sulfur compound) over the compound to be desulfurized. Under these conditions, control experiments on cysteine, methionine, and some other amino acids showed that only the sulfur containing amino acids are degraded by Ni(H). Cysteine and methionine were rapidly converted to alanine and beta-aminobutyric acid, respectively. Gel electrophoresis of the iminothiazolidine peptide after exposure to Ni(H) showed no breakage of the chain.", "contents": "Generation of a free alpha-amino group by Raney nickel after 2-nitro-5-thiocyanobenzoic acid cleavage at cysteine residues: application to automated sequencing. The selective reaction of SH containing proteins and peptides with NTCB (2-nitro-5-thiocyanobenzoic acid) has been reported (Degani, Y., & Patchornick, A. (1974) Biochemistry 13, 1; Jacobson, G.A., Schaffer, M.H., Stark, G.R., & Vanaman, T.C. (1973) J. Biol. Chem. 248, 6583). With this reagent, cysteinyl peptide bonds are selectively cyanylated and subsequently cleaved under alkaline conditions. In the present study we have successfully cleaved the beta-chains of guinea pig hemoglobin at the single cysteine and the peptides thus obtained were separated. However, the C-terminal peptide was blocked at its N terminal by a thiazolidine ring and hence could not be used for Edman degradation sequence analysis. Deblocking of this peptide was successfully done by Raney nickel in the buffer medium of pH 7.0, and also in water, at 50 degrees C for 6 to 10 h. The Raney nickel reagent is used in large excess by weight (at least ten times the weight of sulfur compound) over the compound to be desulfurized. Under these conditions, control experiments on cysteine, methionine, and some other amino acids showed that only the sulfur containing amino acids are degraded by Ni(H). Cysteine and methionine were rapidly converted to alanine and beta-aminobutyric acid, respectively. Gel electrophoresis of the iminothiazolidine peptide after exposure to Ni(H) showed no breakage of the chain."}
{"id": "PMID:215201", "title": "Resonance Raman spectra of whole mitochondria.", "content": "The resonance Raman spectra of reduced cytochromes b and c and cytochrome oxidase in whole mitochondria have been recorded without any instrument modifications. The contributions of the individual cytochromes have been identified by comparison with the characteristic features observed in partially purified preparations including: (i) the strong dependence of the intensity patterns on excitation wavelength relative to the peak positions of the alpha, beta, and gamma absorption bands of the cytochromes; and (ii) the presence of marker bands for heme type. Since the Raman spectra can be used as an intrinsic indicator of interaction between hemes, the ability to record spectra in intact mitochondria opens the possibility to study heme-heme interactions in the functioning membrane in situ.", "contents": "Resonance Raman spectra of whole mitochondria. The resonance Raman spectra of reduced cytochromes b and c and cytochrome oxidase in whole mitochondria have been recorded without any instrument modifications. The contributions of the individual cytochromes have been identified by comparison with the characteristic features observed in partially purified preparations including: (i) the strong dependence of the intensity patterns on excitation wavelength relative to the peak positions of the alpha, beta, and gamma absorption bands of the cytochromes; and (ii) the presence of marker bands for heme type. Since the Raman spectra can be used as an intrinsic indicator of interaction between hemes, the ability to record spectra in intact mitochondria opens the possibility to study heme-heme interactions in the functioning membrane in situ."}
{"id": "PMID:215202", "title": "Cell-free synthesis of herpes simplex virus DNA: the influence of polyamines.", "content": "The effect of polyamines on cell-free DNA synthesis of herpes simplex virus DNA in two different systems is investigated. Purified nuclei from infected cells are devoid of measurable amounts of putrescine, spermidine, and spermine, while an unfractionated lysate contains the polyamines at close to their respective cellular concentrations. Spermine, 0.3 mM, and 0.5 mM spermidine, when added to the nuclear system, decrease the extent of viral DNA synthesis to the level found in the lysate system, the size of the cell-free viral DNA product is increased, and a specific inhibition of repair-type DNA synthesis is observed. These effects of the polyamines occur only in the presence of ATP and not the other three ribonucleoside triphosphates.", "contents": "Cell-free synthesis of herpes simplex virus DNA: the influence of polyamines. The effect of polyamines on cell-free DNA synthesis of herpes simplex virus DNA in two different systems is investigated. Purified nuclei from infected cells are devoid of measurable amounts of putrescine, spermidine, and spermine, while an unfractionated lysate contains the polyamines at close to their respective cellular concentrations. Spermine, 0.3 mM, and 0.5 mM spermidine, when added to the nuclear system, decrease the extent of viral DNA synthesis to the level found in the lysate system, the size of the cell-free viral DNA product is increased, and a specific inhibition of repair-type DNA synthesis is observed. These effects of the polyamines occur only in the presence of ATP and not the other three ribonucleoside triphosphates."}
{"id": "PMID:215203", "title": "Collagen synthesis by human amniotic fluid cells in culture: characterization of a procollagen with three identical proalpha1(I) chains.", "content": "Second trimester human amniotic fluid cells synthesize and secrete a variety of collagenous proteins in culture. F cells (amniotic fluid fibroblasts) are the most active biosynthetically and synthesize predominantly type I with smaller amounts of type III procollagen. Epithelioid AF cells (the predominating clonable cell type) synthesize a type IV-like procollagen and a procollagen with three identical proalpha chains, structurally and immunologically related to the proalpha1 chains of type I procollagen. The latter procollagen, when cleaved with pepsin and denatured, yields a single non-disulfide-bonded alpha chain that migrates more slowly than F cell or human skin alpha1(I) on sodium dodecyl sulfate-polyacrylamide gel electrophoresis but coelutes with these chains from carboxymethyl-cellulose. The major cyanogen bromide produced peptides demonstrate a similar behavior relative to peptides derived from alpha1(I). The collagen is characterized by an increased solubility at neutral pH and high ionic strength, relative to type I collagen. The amino acid composition of the pepsin-resistant alpha chain is essentially identical with that of human alpha1(I), except for marked increases in the content of 3- and 4-hydroxyproline and hydroxylysine. Preliminary experiments suggest that these increased posttranslational modifications are responsible for the unusually slow migration of this collagen and its cyanogen bromide peptides on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The procollagen has, therefore, been assigned the chain composition [proalpha1(I)]3. Like type I procollagen, [proalpha1(I)]3 undergoes a time-dependent conversion, in the medium and cell layer, to procollagen intermediates and alpha chains. The production of [proalpha1(I)]3 probably reflects the state of differentiation and/or embryologic derivation of AF cells rather than a characteristic of the fetal phenotype, since F cells do not synthesize significant amounts of the procollagen.", "contents": "Collagen synthesis by human amniotic fluid cells in culture: characterization of a procollagen with three identical proalpha1(I) chains. Second trimester human amniotic fluid cells synthesize and secrete a variety of collagenous proteins in culture. F cells (amniotic fluid fibroblasts) are the most active biosynthetically and synthesize predominantly type I with smaller amounts of type III procollagen. Epithelioid AF cells (the predominating clonable cell type) synthesize a type IV-like procollagen and a procollagen with three identical proalpha chains, structurally and immunologically related to the proalpha1 chains of type I procollagen. The latter procollagen, when cleaved with pepsin and denatured, yields a single non-disulfide-bonded alpha chain that migrates more slowly than F cell or human skin alpha1(I) on sodium dodecyl sulfate-polyacrylamide gel electrophoresis but coelutes with these chains from carboxymethyl-cellulose. The major cyanogen bromide produced peptides demonstrate a similar behavior relative to peptides derived from alpha1(I). The collagen is characterized by an increased solubility at neutral pH and high ionic strength, relative to type I collagen. The amino acid composition of the pepsin-resistant alpha chain is essentially identical with that of human alpha1(I), except for marked increases in the content of 3- and 4-hydroxyproline and hydroxylysine. Preliminary experiments suggest that these increased posttranslational modifications are responsible for the unusually slow migration of this collagen and its cyanogen bromide peptides on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The procollagen has, therefore, been assigned the chain composition [proalpha1(I)]3. Like type I procollagen, [proalpha1(I)]3 undergoes a time-dependent conversion, in the medium and cell layer, to procollagen intermediates and alpha chains. The production of [proalpha1(I)]3 probably reflects the state of differentiation and/or embryologic derivation of AF cells rather than a characteristic of the fetal phenotype, since F cells do not synthesize significant amounts of the procollagen."}
{"id": "PMID:215204", "title": "Kinetic mechanism of Escherichia coli carbamoyl-phosphate synthetase.", "content": "The kinetic mechanism of Escherichia coli carbamoyl-phosphate synthetase has been determined at pH 7.5, 25 degrees C. With ammonia as the nitrogen source, the initial velocity and product inhibition patterns are consistent with the ordered addition of MgATP, HCO3-, and NH3. Phosphate is then released and the second MgATP adds to the enzyme, which is followed by the ordered release of MgADP, carbamoyl phosphate, and MgADP. With glutamine as the ammonia donor, the patterns are consistent with a two-site mechanism in which glutamine binds randomly to the small molecular weight subunit producing glutamate and ammonia. Glutamate is released and the ammonia is transferred to the larger subunit. Carbamoyl-phosphate synthetase has also been shown to require a free divalent cation for full activity.", "contents": "Kinetic mechanism of Escherichia coli carbamoyl-phosphate synthetase. The kinetic mechanism of Escherichia coli carbamoyl-phosphate synthetase has been determined at pH 7.5, 25 degrees C. With ammonia as the nitrogen source, the initial velocity and product inhibition patterns are consistent with the ordered addition of MgATP, HCO3-, and NH3. Phosphate is then released and the second MgATP adds to the enzyme, which is followed by the ordered release of MgADP, carbamoyl phosphate, and MgADP. With glutamine as the ammonia donor, the patterns are consistent with a two-site mechanism in which glutamine binds randomly to the small molecular weight subunit producing glutamate and ammonia. Glutamate is released and the ammonia is transferred to the larger subunit. Carbamoyl-phosphate synthetase has also been shown to require a free divalent cation for full activity."}
{"id": "PMID:215205", "title": "Dependence of boundary lipid on fatty acid chain length in phosphatidylcholine vesicles containing a hydrophobic protein from myelin proteolipid.", "content": "Lipophilin, a hydrophobic protein fraction, purified and delipidated from the proteolipid of human myelin, possesses a layer of boundary lipid surrounding it when incorporated into lipid vesicles. The protein reduces the energy absorbed during the lipid phase transition, indicating that the boundary lipid does not go through the phase transition. The amount of boundary lipid was estimated by plotting the enthalpy of the transition against the protein to lipid mole ratio and extrapolating to deltaH = 0 for a number of synthetic phosphatidylcholines, to determine the ability of fatty acid chains of varying length to interact with the protein. The amount of boundary lipid was found to be similar, 21-25 molecules per molecule of lipophilin, for fatty acid chains of length 14-18 carbons but somewhat less, 16 molecules of lipid per molecule of protein, for a fatty acid chain length of 12 or for one with a trans double bond (18:1tr). No preferential interaction was observed with a lipid containing a particular fatty acid chain length when the protein was incorporated into a mixture of these lipids. These results suggest that the binding of lipids to the boundary layer of other membrane proteins and enzymes may not depend significantly on lipid fatty acid chain length.", "contents": "Dependence of boundary lipid on fatty acid chain length in phosphatidylcholine vesicles containing a hydrophobic protein from myelin proteolipid. Lipophilin, a hydrophobic protein fraction, purified and delipidated from the proteolipid of human myelin, possesses a layer of boundary lipid surrounding it when incorporated into lipid vesicles. The protein reduces the energy absorbed during the lipid phase transition, indicating that the boundary lipid does not go through the phase transition. The amount of boundary lipid was estimated by plotting the enthalpy of the transition against the protein to lipid mole ratio and extrapolating to deltaH = 0 for a number of synthetic phosphatidylcholines, to determine the ability of fatty acid chains of varying length to interact with the protein. The amount of boundary lipid was found to be similar, 21-25 molecules per molecule of lipophilin, for fatty acid chains of length 14-18 carbons but somewhat less, 16 molecules of lipid per molecule of protein, for a fatty acid chain length of 12 or for one with a trans double bond (18:1tr). No preferential interaction was observed with a lipid containing a particular fatty acid chain length when the protein was incorporated into a mixture of these lipids. These results suggest that the binding of lipids to the boundary layer of other membrane proteins and enzymes may not depend significantly on lipid fatty acid chain length."}
{"id": "PMID:215210", "title": "The role of arginine residues in the function of D-glyceraldehyde-3-phosphate dehydrogenase.", "content": "Inactivation of apo-glyceraldehyde-3-phosphate dehydrogenase from rat skeletal muscle in the presence of butanedione is the result of modification of one arginyl residue per subunit of the tetrameric enzyme molecule. The loss of activity follows pseudo-first-order kinetics. NAD+ increases the apparent first-order rate constant of inactivation. The effect of NAD+ on the enzyme inactivation is cooperative (Hill coefficient = 2.3--3.2). Glyceraldehyde 3-phosphate protected the holoenzyme against inactivation, decreasing the rate constant of the reaction. At saturating concentrations of substrate the protection was complete. The Hill plot demonstrates that the effect is cooperative. This suggests that subunit interactions in the tetrameric holoenzyme molecule may affect the reactivity of the essential arginyl residues. In contrast, glyceraldehyde 3-phosphate had no effect on the rate of inactivation of the apoenzyme in the presence of butanedione. 100 mM inorganic phosphate protected both the apoenzyme and holoenzyme against inactivation. The involvement of the microenvironment of the arginyl residues in the functionally important conformational changes of the enzyme is discussed.", "contents": "The role of arginine residues in the function of D-glyceraldehyde-3-phosphate dehydrogenase. Inactivation of apo-glyceraldehyde-3-phosphate dehydrogenase from rat skeletal muscle in the presence of butanedione is the result of modification of one arginyl residue per subunit of the tetrameric enzyme molecule. The loss of activity follows pseudo-first-order kinetics. NAD+ increases the apparent first-order rate constant of inactivation. The effect of NAD+ on the enzyme inactivation is cooperative (Hill coefficient = 2.3--3.2). Glyceraldehyde 3-phosphate protected the holoenzyme against inactivation, decreasing the rate constant of the reaction. At saturating concentrations of substrate the protection was complete. The Hill plot demonstrates that the effect is cooperative. This suggests that subunit interactions in the tetrameric holoenzyme molecule may affect the reactivity of the essential arginyl residues. In contrast, glyceraldehyde 3-phosphate had no effect on the rate of inactivation of the apoenzyme in the presence of butanedione. 100 mM inorganic phosphate protected both the apoenzyme and holoenzyme against inactivation. The involvement of the microenvironment of the arginyl residues in the functionally important conformational changes of the enzyme is discussed."}
{"id": "PMID:215211", "title": "Characterization of two adenosine 3':5'-phosphate-dependent protein kinase species from Chinese hamster ovary cells.", "content": "Chinese hamster ovary cells exhibit several characteristic morphological and physiological responses upon treatment with agents which increase the intracellular level of adenosine 3':5'-phosphate (cyclic AMP). To better understand the mechanism of these cyclic AMP-mediated responses, we separated two cyclic AMP-dependent protein kinases (ATP:protein phosphotransferase, EC 2.7.1.37) (protein kinase I and protein kinase II) from the cytosol of Chinese hamster ovary cells by DEAE-cellulose chromatography and studied their properties. Protein kinase I is eluted at a lower salt concentration than protein kinase II and is stimulable to 10 times its basal catalytic activity, while protein kinase II is stimulable only 2-fold. Both kinases are completely dissociated by cyclic AMP and inhibited by specific cyclic AMP-dependent protein kinase inhibitor. They have similar Km values for magnesium (approximately 1 mM), cyclic AMP (approximately 60 nM), and ATP (approximately 0.1 mM), and the dissociation constant (Kdis) for cyclic AMP (approximately 13 nM) is the same for both enzymes. However, they appear to have different substrate preferences and cyclic AMP-binding properties in that cyclic AMP bound to protein kinase II exchanges readily with free cyclic AMP, while that bound to protein kinase I is not exchangeable. The native enzymes have different sedimentation coefficients (6.4 S for protein kinase I and 4.8 S for protein kinase II), whereas those of the activated enzymes are the same (2.9--3.0 S). It appears that the two cyclic AMP-dependent protein kinases which differ from each other in their regulatory subunits may play different roles in the mediation of cyclic AMP action in Chinese hamster ovary cells.", "contents": "Characterization of two adenosine 3':5'-phosphate-dependent protein kinase species from Chinese hamster ovary cells. Chinese hamster ovary cells exhibit several characteristic morphological and physiological responses upon treatment with agents which increase the intracellular level of adenosine 3':5'-phosphate (cyclic AMP). To better understand the mechanism of these cyclic AMP-mediated responses, we separated two cyclic AMP-dependent protein kinases (ATP:protein phosphotransferase, EC 2.7.1.37) (protein kinase I and protein kinase II) from the cytosol of Chinese hamster ovary cells by DEAE-cellulose chromatography and studied their properties. Protein kinase I is eluted at a lower salt concentration than protein kinase II and is stimulable to 10 times its basal catalytic activity, while protein kinase II is stimulable only 2-fold. Both kinases are completely dissociated by cyclic AMP and inhibited by specific cyclic AMP-dependent protein kinase inhibitor. They have similar Km values for magnesium (approximately 1 mM), cyclic AMP (approximately 60 nM), and ATP (approximately 0.1 mM), and the dissociation constant (Kdis) for cyclic AMP (approximately 13 nM) is the same for both enzymes. However, they appear to have different substrate preferences and cyclic AMP-binding properties in that cyclic AMP bound to protein kinase II exchanges readily with free cyclic AMP, while that bound to protein kinase I is not exchangeable. The native enzymes have different sedimentation coefficients (6.4 S for protein kinase I and 4.8 S for protein kinase II), whereas those of the activated enzymes are the same (2.9--3.0 S). It appears that the two cyclic AMP-dependent protein kinases which differ from each other in their regulatory subunits may play different roles in the mediation of cyclic AMP action in Chinese hamster ovary cells."}
{"id": "PMID:215212", "title": "Phospho-N-acetylmuramoyl-pentapeptide-transferase of Escherichia coli K12. Properties of the membrane-bound and the extracted and partially purified enzyme.", "content": "Phospho-N-acetylmuramoyl-pentapeptide-transferase (UDP-N-acetyl-muramoyl-L-alanyl-D-gamma-glutamyl-L-lysyl-D-alanyl-D-alanine:undecaprenoid-alcohol-phosphate-phospho-N-acetylmuramoyl-pentapeptide-transferase, EC 2.7.8.13) was solubilized by repeated freezing and thawing of crude envelopes of Escherichia coli K12. The solubilized enzyme was partially purified by gel filtration and ion-exchange chromatography. This preparation contained small amounts of phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol but no endogenous lipid substrate, C55-isoprenyl phosphate, could be detected. Some catalytic properties (exchange reaction) of the solubilized enzyme were compared to those of membrane-bound transferase. The transfer activity of the partially purified transferase was restored by the addition of an aqueous lipid dispersion. All the transferase activity was found to become incorporated into the liposomes. Preincubation of the transferase preparation with phospholipase A2 or D strongly reduce both exchange and transfer activity. This suggests that phospholipids sensitive to phospholipases are necessary for the enzymatic reaction. Different effects of some neutral detergents on the exchange activity were reported.", "contents": "Phospho-N-acetylmuramoyl-pentapeptide-transferase of Escherichia coli K12. Properties of the membrane-bound and the extracted and partially purified enzyme. Phospho-N-acetylmuramoyl-pentapeptide-transferase (UDP-N-acetyl-muramoyl-L-alanyl-D-gamma-glutamyl-L-lysyl-D-alanyl-D-alanine:undecaprenoid-alcohol-phosphate-phospho-N-acetylmuramoyl-pentapeptide-transferase, EC 2.7.8.13) was solubilized by repeated freezing and thawing of crude envelopes of Escherichia coli K12. The solubilized enzyme was partially purified by gel filtration and ion-exchange chromatography. This preparation contained small amounts of phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol but no endogenous lipid substrate, C55-isoprenyl phosphate, could be detected. Some catalytic properties (exchange reaction) of the solubilized enzyme were compared to those of membrane-bound transferase. The transfer activity of the partially purified transferase was restored by the addition of an aqueous lipid dispersion. All the transferase activity was found to become incorporated into the liposomes. Preincubation of the transferase preparation with phospholipase A2 or D strongly reduce both exchange and transfer activity. This suggests that phospholipids sensitive to phospholipases are necessary for the enzymatic reaction. Different effects of some neutral detergents on the exchange activity were reported."}
{"id": "PMID:215213", "title": "Activation of mammalian cyclic AMP phosphodiesterases by trypsin.", "content": "BHK fibroblasts contain two forms of cyclic AMP phosphodiesterase 3':5'-cyclic nucleotide 5'-nucleotidohydrolase EC 3.1.4.17) as analyzed by linear sucrose gradient fractionation; a 3.6-S form (peak I) and a 6.7-S form (peak II). Peak I is specific for cyclic AMP as substrate and displays Michaelis-Menten kinetics with an apparent Km of 2--3 micrometer. Peak II hydrolyzes cyclic GMP and displays anomalous kinetics for cyclic AMP hydrolysis. The activity of isolated peak II for cyclic AMP is increased by storage at 4 degrees C, treatment with trypsin, or treatment with rat brain and BHK fibroblast activator proteins. The activity of isolated peak I is unaffected by these conditions. Linear sucrose gradient fractionation demonstrates that activation of peak II by trypsin leads to the formation of a 3.6-S cyclic AMP-specific enzyme form, possibly peak I. In contrast to BHK fibroblasts (and most other mammalian tissues), rat uterus contains only one form of cyclic nucleotide phosphodiesterase on linear sucrose gradients, a 7-S form capable of hydrolyzing both cyclic AMP and cyclic GMP. Treatment of rat uterine supernatant with trypsin leads to the appearance of a 4-S, cyclic AMP-specific form with properties similar to that of BHK peak I. These data suggest that the kinetically complex, higher molecular weight cyclic nucleotide phosphodiesterases may consist of more than one catalytically active site and that multiple forms of the enzyme arise through dissociative mechanisms, possibly as a means of in vivo regulation.", "contents": "Activation of mammalian cyclic AMP phosphodiesterases by trypsin. BHK fibroblasts contain two forms of cyclic AMP phosphodiesterase 3':5'-cyclic nucleotide 5'-nucleotidohydrolase EC 3.1.4.17) as analyzed by linear sucrose gradient fractionation; a 3.6-S form (peak I) and a 6.7-S form (peak II). Peak I is specific for cyclic AMP as substrate and displays Michaelis-Menten kinetics with an apparent Km of 2--3 micrometer. Peak II hydrolyzes cyclic GMP and displays anomalous kinetics for cyclic AMP hydrolysis. The activity of isolated peak II for cyclic AMP is increased by storage at 4 degrees C, treatment with trypsin, or treatment with rat brain and BHK fibroblast activator proteins. The activity of isolated peak I is unaffected by these conditions. Linear sucrose gradient fractionation demonstrates that activation of peak II by trypsin leads to the formation of a 3.6-S cyclic AMP-specific enzyme form, possibly peak I. In contrast to BHK fibroblasts (and most other mammalian tissues), rat uterus contains only one form of cyclic nucleotide phosphodiesterase on linear sucrose gradients, a 7-S form capable of hydrolyzing both cyclic AMP and cyclic GMP. Treatment of rat uterine supernatant with trypsin leads to the appearance of a 4-S, cyclic AMP-specific form with properties similar to that of BHK peak I. These data suggest that the kinetically complex, higher molecular weight cyclic nucleotide phosphodiesterases may consist of more than one catalytically active site and that multiple forms of the enzyme arise through dissociative mechanisms, possibly as a means of in vivo regulation."}
{"id": "PMID:215214", "title": "Activation by lithium ions of the inside sodium sites in (Na+ + K+)-ATPase.", "content": "1. Purified pig kidney ATPase was incubated in 30--160 mM Tris-HCl with various monovalent cations. 130 mM LiCl stimulated a ouabain-sensitive ATP hydrolysis (about 5% of the maximal (Na+ + K) activity), whereas 160 mM Tris-HCl did not stimulate hydrolysis. Similar results were obtained with human red blood cell broken membranes. 2. In the absence of Na+ and with 130 mM LiCl, the ATPase activity as a function of KCl concentration showed an initial slight inhibition (50 micrometer KCl) followed by an activation (maximal at 0.2 mM KCl) and a further inhibition, which was total at mM KCl. In the absence of LiCl, the rate of hydrolysis was not affected by any of the KCl concentrations investigated. 3. The lithium-activation curve for ATPase activity in the absence of both Na+ and K+ had sigmoid characteristics. It also showed a marked dependence on the total LiCl + Tris-HCl concentration, being inhibited at high concentrations. This inhibition was more noticeable at low LiCl concentrations. 4. In the absence of Na+, 130 mM Li+ showed promoted phosphorylation of ATPase from 1 to 3 mM ATP in the presence of Mg2+. In enzyme treated with N-ethylmaleimide, the levels of phosphorylation in Li+-containing solutions, amounted to 40% of those in Na+- and up to 7 times of those in K+-containing solutions. 5. The total (Na+ + K+)-ATPase activity was markedly inhibited at high buffer concentrations (Tris-HCl, Imidazole-HCl and tetramethylammonium-HEPES gave similar results) in cases when either the concentration of Na+ or K+ (or both) was below saturation. On the other hand, the maximal (Na+ + K+)-ATPase activity was not affected (or very slightly) by the buffer concentration. 6. Under standard conditions (Tris-HCl + NaCl = 160 mM) the Na+-activation curve of Na+-ATPase had a steep rise between 0 and 2.5 mM, a fall between 2.5 and 20 mM and a further increase between 20 and 130 mM. With 30 mM Tris-HCl, the curve rose more steeply, inhibition was noticeable at 2.5 mM Na+ and was completed at 5 mM Na+. With Tris-HCl + NaCl = 280 mM, the amount of activation decreased and inhibition at intermediate Na+ concentrations was not detected.", "contents": "Activation by lithium ions of the inside sodium sites in (Na+ + K+)-ATPase. 1. Purified pig kidney ATPase was incubated in 30--160 mM Tris-HCl with various monovalent cations. 130 mM LiCl stimulated a ouabain-sensitive ATP hydrolysis (about 5% of the maximal (Na+ + K) activity), whereas 160 mM Tris-HCl did not stimulate hydrolysis. Similar results were obtained with human red blood cell broken membranes. 2. In the absence of Na+ and with 130 mM LiCl, the ATPase activity as a function of KCl concentration showed an initial slight inhibition (50 micrometer KCl) followed by an activation (maximal at 0.2 mM KCl) and a further inhibition, which was total at mM KCl. In the absence of LiCl, the rate of hydrolysis was not affected by any of the KCl concentrations investigated. 3. The lithium-activation curve for ATPase activity in the absence of both Na+ and K+ had sigmoid characteristics. It also showed a marked dependence on the total LiCl + Tris-HCl concentration, being inhibited at high concentrations. This inhibition was more noticeable at low LiCl concentrations. 4. In the absence of Na+, 130 mM Li+ showed promoted phosphorylation of ATPase from 1 to 3 mM ATP in the presence of Mg2+. In enzyme treated with N-ethylmaleimide, the levels of phosphorylation in Li+-containing solutions, amounted to 40% of those in Na+- and up to 7 times of those in K+-containing solutions. 5. The total (Na+ + K+)-ATPase activity was markedly inhibited at high buffer concentrations (Tris-HCl, Imidazole-HCl and tetramethylammonium-HEPES gave similar results) in cases when either the concentration of Na+ or K+ (or both) was below saturation. On the other hand, the maximal (Na+ + K+)-ATPase activity was not affected (or very slightly) by the buffer concentration. 6. Under standard conditions (Tris-HCl + NaCl = 160 mM) the Na+-activation curve of Na+-ATPase had a steep rise between 0 and 2.5 mM, a fall between 2.5 and 20 mM and a further increase between 20 and 130 mM. With 30 mM Tris-HCl, the curve rose more steeply, inhibition was noticeable at 2.5 mM Na+ and was completed at 5 mM Na+. With Tris-HCl + NaCl = 280 mM, the amount of activation decreased and inhibition at intermediate Na+ concentrations was not detected."}
{"id": "PMID:215215", "title": "Nitrogenase X: M\u00f6ssbauer and EPR studies on reversibly oxidized MoFe protein from Azotobacter vinelandii OP. Nature of the iron centers.", "content": "Under anaerobic conditions the molybdenum-iron protein (MoFe protein) from Azotobacter vinelandii can be reversibly oxidized with thionine. Electron paramagnetic resonance studies reveal that the oxidation proceeds in two distinct phases: the MoFe protein can be oxidized by four electrons without loss of the EPR signal from the S = 3/2 cofactor centers. A second oxidation step, involving two electrons, leads to the disappearance of the cofactor EPR signal. In order to correlate the events during the thionine titration with redox reactions involving individual iron centers we have studied the MoFe proteins from A vinelandii and Clostridium pasteurianum with M\u00f6ssbauer spectroscopy. Spectra were taken in the temperature range from 1.5 K to 200 K in applied magnetic fields of up to 54 kG. Analysis of the M\u00f6ssbauer data allows us to draw three major conclusions: (1) the holoprotein contains 30 +/- 2 iron atoms. (2) Most probably, 12 iron atoms belong to two, apparently identical, iron clusters (labeled M) which we have shown previously to be structural components of the iron and molybdenum containing cofactor of nitrogenase. The M-centers can be stabilized in three distinct oxidation states, MOXe- in equilibrium MNe- in equilibrium MR. The diamagnetic (S = 0) state MOX is attained by oxidation of the native state MN with either thionine or oxygen. MR is observed under nitrogen fixing conditions. (3) The data strongly suggest that 16 iron atoms are associated with four iron centers which we propose to call P-clusters. Each P-cluster contains four spin-coupled iron atoms. In the native protein the P-clusters are in the diamagnetic state PN, yielding the M\u00f6ssbauer signature which we have labeled previously 'components D and Fe2+'. Three irons of the D-type and one iron of the Fe2+-type appear to comprise a P-cluster. A one-electron oxidation yields the paramagnetic state POX. Although the state POX is characterized by half-integral electronic spin a peculiar combination of zero-field splitting parameters and spin relaxation renders this state EPR-silent. Spectroscopically, the P-clusters are novel structures; there is, however, evidence that they are closely related to familiar 4Fe-4S centers.", "contents": "Nitrogenase X: M\u00f6ssbauer and EPR studies on reversibly oxidized MoFe protein from Azotobacter vinelandii OP. Nature of the iron centers. Under anaerobic conditions the molybdenum-iron protein (MoFe protein) from Azotobacter vinelandii can be reversibly oxidized with thionine. Electron paramagnetic resonance studies reveal that the oxidation proceeds in two distinct phases: the MoFe protein can be oxidized by four electrons without loss of the EPR signal from the S = 3/2 cofactor centers. A second oxidation step, involving two electrons, leads to the disappearance of the cofactor EPR signal. In order to correlate the events during the thionine titration with redox reactions involving individual iron centers we have studied the MoFe proteins from A vinelandii and Clostridium pasteurianum with M\u00f6ssbauer spectroscopy. Spectra were taken in the temperature range from 1.5 K to 200 K in applied magnetic fields of up to 54 kG. Analysis of the M\u00f6ssbauer data allows us to draw three major conclusions: (1) the holoprotein contains 30 +/- 2 iron atoms. (2) Most probably, 12 iron atoms belong to two, apparently identical, iron clusters (labeled M) which we have shown previously to be structural components of the iron and molybdenum containing cofactor of nitrogenase. The M-centers can be stabilized in three distinct oxidation states, MOXe- in equilibrium MNe- in equilibrium MR. The diamagnetic (S = 0) state MOX is attained by oxidation of the native state MN with either thionine or oxygen. MR is observed under nitrogen fixing conditions. (3) The data strongly suggest that 16 iron atoms are associated with four iron centers which we propose to call P-clusters. Each P-cluster contains four spin-coupled iron atoms. In the native protein the P-clusters are in the diamagnetic state PN, yielding the M\u00f6ssbauer signature which we have labeled previously 'components D and Fe2+'. Three irons of the D-type and one iron of the Fe2+-type appear to comprise a P-cluster. A one-electron oxidation yields the paramagnetic state POX. Although the state POX is characterized by half-integral electronic spin a peculiar combination of zero-field splitting parameters and spin relaxation renders this state EPR-silent. Spectroscopically, the P-clusters are novel structures; there is, however, evidence that they are closely related to familiar 4Fe-4S centers."}
{"id": "PMID:215216", "title": "Electron nuclear double resonance of cytochrome oxidase: nitrogen and proton ENDOR from the 'copper' EPR signal.", "content": "Proton ENDOR resonances have been found from at least two different protons with fairly large and isotropic couplings of about 12 and 19 MHz. It is possible that such protons are attached to carbons that are one bond removed from the point of ligation to copper. A number of weakly coupled protons with anisotropic couplings have also been seen. None of the protons, either weakly or strongly coupled, appears to exchange with 2H2O. We have obtained nitrogen ENDOR from at least one nitrogen with a hyperfine coupling large enough for the nitrogen to be a ligand of copper. We have not yet demonstrated experimentally ENDOR characteristic of the copper nucleus itself.", "contents": "Electron nuclear double resonance of cytochrome oxidase: nitrogen and proton ENDOR from the 'copper' EPR signal. Proton ENDOR resonances have been found from at least two different protons with fairly large and isotropic couplings of about 12 and 19 MHz. It is possible that such protons are attached to carbons that are one bond removed from the point of ligation to copper. A number of weakly coupled protons with anisotropic couplings have also been seen. None of the protons, either weakly or strongly coupled, appears to exchange with 2H2O. We have obtained nitrogen ENDOR from at least one nitrogen with a hyperfine coupling large enough for the nitrogen to be a ligand of copper. We have not yet demonstrated experimentally ENDOR characteristic of the copper nucleus itself."}
{"id": "PMID:215217", "title": "Electron spin relaxation of iron-sulphur proteins studied by microwave power saturation.", "content": "The electron-spin relaxation of iron-sulphur centres in a range of simple proteins (ferredoxin, high-potential iron-sulphur protein and rubredoxin) was investigated by means of the temperature dependence and microwave power saturation of the EPR signal. The proteins containing [2Fe-2S] centres all showed temperature optima higher than those for [4Fe-4S] centres, but the difference between the slowest-relaxing [4Fe-4S] protein (Chromatium high-potential iron-sulphur protein) and the fastest-relaxing [2Fe-2S] protein (Halobacterium halobium ferredoxin) was small. A greater distinction was seen in the power saturation behaviour at low temperature (10--20 K). The behaviour of the signal intensity as a function of microwave power was analyzed in terms of the power for half saturation P 1/2 and the degree of homogeneous/inhomogeneous broadening. The effect of distorting the protein structure by salts, organic solvents and urea was to decrease the electron-spin relaxation rate as shown by a decreased value of P 1/2. The addition of Ni2+ as a paramagnetic perturbing agent caused an increase in the electron-spin relaxation rate of all the proteins, with the exception of adrenal ferredoxin, as shown by an increased P 1/2 and, in a few cases, broadening of the linewidth. Ferricyanide, a commonly used oxidizing agent, has similar effects. These results are discussed in relation to the use of paramagnetic probes to determine whether iron-sulphur centres are near to a membrane surface. Spin-spin interactions between two paramagnetic centres in a protein molecule such as a 2[4Fe-4S] ferredoxin, lead to more rapid electron-spin relaxation. This method was used to detect a spin-spin interaction between molybdenum V and centre Fe-SI in xanthine oxidase.", "contents": "Electron spin relaxation of iron-sulphur proteins studied by microwave power saturation. The electron-spin relaxation of iron-sulphur centres in a range of simple proteins (ferredoxin, high-potential iron-sulphur protein and rubredoxin) was investigated by means of the temperature dependence and microwave power saturation of the EPR signal. The proteins containing [2Fe-2S] centres all showed temperature optima higher than those for [4Fe-4S] centres, but the difference between the slowest-relaxing [4Fe-4S] protein (Chromatium high-potential iron-sulphur protein) and the fastest-relaxing [2Fe-2S] protein (Halobacterium halobium ferredoxin) was small. A greater distinction was seen in the power saturation behaviour at low temperature (10--20 K). The behaviour of the signal intensity as a function of microwave power was analyzed in terms of the power for half saturation P 1/2 and the degree of homogeneous/inhomogeneous broadening. The effect of distorting the protein structure by salts, organic solvents and urea was to decrease the electron-spin relaxation rate as shown by a decreased value of P 1/2. The addition of Ni2+ as a paramagnetic perturbing agent caused an increase in the electron-spin relaxation rate of all the proteins, with the exception of adrenal ferredoxin, as shown by an increased P 1/2 and, in a few cases, broadening of the linewidth. Ferricyanide, a commonly used oxidizing agent, has similar effects. These results are discussed in relation to the use of paramagnetic probes to determine whether iron-sulphur centres are near to a membrane surface. Spin-spin interactions between two paramagnetic centres in a protein molecule such as a 2[4Fe-4S] ferredoxin, lead to more rapid electron-spin relaxation. This method was used to detect a spin-spin interaction between molybdenum V and centre Fe-SI in xanthine oxidase."}
{"id": "PMID:215218", "title": "Isolation and partial characterization of secreted mouse pituitary prolactin.", "content": "Prolactin secreted by mouse anterior pituitaries was purified by gel filtration on Sephadex G-100. Electrophoretic homogeneity of the purified hormone was demonstrated in several gel systems, and electrophoresis in the presence of sodium dodecyl sulfate indicated an apparent molecular weight of 21 000 +/- 2000. Mouse and ovine prolactin displayed parallel dose vs. response curves in radio-receptor binding studies, indicating that these two hormones compete for identical receptor sites on rabbit mammary membranes. Comparative peptide mapping studies carried out on tryptic digests of mouse and ovine prolactin suggested only partial homology between the two hormones. Internally labeled monomeric mouse prolactin was observed to undergo aggregation following storage at --20 degrees C for 2 months.", "contents": "Isolation and partial characterization of secreted mouse pituitary prolactin. Prolactin secreted by mouse anterior pituitaries was purified by gel filtration on Sephadex G-100. Electrophoretic homogeneity of the purified hormone was demonstrated in several gel systems, and electrophoresis in the presence of sodium dodecyl sulfate indicated an apparent molecular weight of 21 000 +/- 2000. Mouse and ovine prolactin displayed parallel dose vs. response curves in radio-receptor binding studies, indicating that these two hormones compete for identical receptor sites on rabbit mammary membranes. Comparative peptide mapping studies carried out on tryptic digests of mouse and ovine prolactin suggested only partial homology between the two hormones. Internally labeled monomeric mouse prolactin was observed to undergo aggregation following storage at --20 degrees C for 2 months."}
{"id": "PMID:215219", "title": "Properties of adenylate kinase after modification of Arg-97 by phenylglyoxal.", "content": "Adenylate kinase (ATP:AMP phosphotransferase, EC 2.7.4.3) isolated from porcine skeletal and heart muscle and from rabbit muscle are inactivated when a single arginine residue is modified. In adenylate kinase from pig the modified residue was identified as Arg-97 by peptide-mapping. In native adenylate kinase Arg-97 is located at the bottom of the active site cleft. The protein fluorescence of modified adenylate kinase is reduced. Whereas the addition of AMP, ADP and MgATP quench the fluorescence of native adenylate kinase, the fluorescence of phenylglyoxal-modified adenylate kinase is only affected by ADP and MgATP. This finding is discussed in connection with the structural isomerization observed in native adenylate kinase by X-ray diffraction analysis.", "contents": "Properties of adenylate kinase after modification of Arg-97 by phenylglyoxal. Adenylate kinase (ATP:AMP phosphotransferase, EC 2.7.4.3) isolated from porcine skeletal and heart muscle and from rabbit muscle are inactivated when a single arginine residue is modified. In adenylate kinase from pig the modified residue was identified as Arg-97 by peptide-mapping. In native adenylate kinase Arg-97 is located at the bottom of the active site cleft. The protein fluorescence of modified adenylate kinase is reduced. Whereas the addition of AMP, ADP and MgATP quench the fluorescence of native adenylate kinase, the fluorescence of phenylglyoxal-modified adenylate kinase is only affected by ADP and MgATP. This finding is discussed in connection with the structural isomerization observed in native adenylate kinase by X-ray diffraction analysis."}
{"id": "PMID:215220", "title": "The interaction of liver alcohol dehydrogenase with NADH as studied by differential protein denaturation.", "content": "Heat denaturation of horse liver alcohol dehydrogenase was followed in the presence of isobutyramide at various degrees of saturation of the binding sites by NADH. A study of the fluorescence enhancement which is observed when an excess of NADH is added to the partially denatured mixtures provides information regarding the relative concentrations of mono- and bioccupied enzyme molecules. This approach is of value in situations when the association constants for coenzyme are so large that the concentration of the free ligand is negligible. The results obtained indicate that the binding of NADH to liver alcohol dehydrogenase follows the statistically predicted distribution. At the same time evidence was obtained for interaction between the two subunits of the enzyme.", "contents": "The interaction of liver alcohol dehydrogenase with NADH as studied by differential protein denaturation. Heat denaturation of horse liver alcohol dehydrogenase was followed in the presence of isobutyramide at various degrees of saturation of the binding sites by NADH. A study of the fluorescence enhancement which is observed when an excess of NADH is added to the partially denatured mixtures provides information regarding the relative concentrations of mono- and bioccupied enzyme molecules. This approach is of value in situations when the association constants for coenzyme are so large that the concentration of the free ligand is negligible. The results obtained indicate that the binding of NADH to liver alcohol dehydrogenase follows the statistically predicted distribution. At the same time evidence was obtained for interaction between the two subunits of the enzyme."}
{"id": "PMID:215221", "title": "Cyclic AMP-binding proteins and protamine kinases in porcine thyroid cytosol.", "content": "Partial purification of cyclic AMP-binding proteins from porcine thyroid cytosol was performed by gel filtration on Bio Gel 1.5 m followed by ion exchange chromatography on DEAE Sephadex A25. Three fractions presenting cyclic AMP-binding activities were resolved by gel filtration (I, II, III). Approximate molecular weights were respectively 280 000, 145 000 and 65 000. Fraction I was further resolved into two peaks (Ialpha and Ibeta) on DEAE-Sephadex A25. Fractions I, Ialpha, Ibeta comigrated with protein kinase activity whereas peaks II and III did not. These fractions differed with respect to the folling characteristics: rate and stability of cyclic AMP binding to isolated fractions were differently affected by pH (4.0 or 7.5). Electrophoretic mobility on polyacrylamide gels (5%) of fractions preincubated with cyclic [3H]AMP showed similar mobilities for Ialpha, Ibeta or II (Rf 0.37) whereas fraction III displayed a much greater mobility (RF 0.73); Scatchard plots were linear for fractions Ialpha, II and III with an apparent Kd in the same range (2 to 5 nM) whereas fraction Ibeta generated a biphasic plot with Kd 0.4 nM and 20 nM; cyclic [3H] AMP added to fraction I, Ialpha or Ibeta generated a cyclic [3H] AMP-binding protein complex of lower molecular weight as shown by Sephadex G 150 filtration; on the basis of the elution volume, this complex was not distinguished from fraction II. In the course of this work, we separated at the first step of purification (Bio Gel 1.5 m) a protein kinase not associated with cyclic AMP binding activity which exhibited marked specificity for protamine as compared to histone II A.", "contents": "Cyclic AMP-binding proteins and protamine kinases in porcine thyroid cytosol. Partial purification of cyclic AMP-binding proteins from porcine thyroid cytosol was performed by gel filtration on Bio Gel 1.5 m followed by ion exchange chromatography on DEAE Sephadex A25. Three fractions presenting cyclic AMP-binding activities were resolved by gel filtration (I, II, III). Approximate molecular weights were respectively 280 000, 145 000 and 65 000. Fraction I was further resolved into two peaks (Ialpha and Ibeta) on DEAE-Sephadex A25. Fractions I, Ialpha, Ibeta comigrated with protein kinase activity whereas peaks II and III did not. These fractions differed with respect to the folling characteristics: rate and stability of cyclic AMP binding to isolated fractions were differently affected by pH (4.0 or 7.5). Electrophoretic mobility on polyacrylamide gels (5%) of fractions preincubated with cyclic [3H]AMP showed similar mobilities for Ialpha, Ibeta or II (Rf 0.37) whereas fraction III displayed a much greater mobility (RF 0.73); Scatchard plots were linear for fractions Ialpha, II and III with an apparent Kd in the same range (2 to 5 nM) whereas fraction Ibeta generated a biphasic plot with Kd 0.4 nM and 20 nM; cyclic [3H] AMP added to fraction I, Ialpha or Ibeta generated a cyclic [3H] AMP-binding protein complex of lower molecular weight as shown by Sephadex G 150 filtration; on the basis of the elution volume, this complex was not distinguished from fraction II. In the course of this work, we separated at the first step of purification (Bio Gel 1.5 m) a protein kinase not associated with cyclic AMP binding activity which exhibited marked specificity for protamine as compared to histone II A."}
{"id": "PMID:215222", "title": "Particulate enhanced membrane uptake of 1,2-benzanthracene observed by fluorescence spectroscopy: a possible role in co-carcinogenesis.", "content": "In recognition of the co-carcinogenic effects of particulate matter and chemical carcinogens, we investigated the effect of particulate silica on the rates of membrane uptake of 1,2-benzanthracene. The fluorescence emission spectra and the apparent quantum yields of benzanthracene and dependent upon adsorption to silica and upon the surface density of benzanthracene on the silica. The fluorescence spectral shifts which occur upon transfer of benzanthracene from the silica surface to phospholipid vesicles provided a convenient means to quantitate the membrane uptake of benzanthracene from particulates. The rate of benzanthracene uptake by dipalmitoyl-L-alpha-phosphatidylcholine vesicles was independent of the concentration of lipid, indicating that the rate-limiting step may involve its solubilization in the aqueous phase. These uptake rates were also independent of the surface density of benzanthracene on the silica, indicating that the benzathracene molecules are dispersed uniformly on the silica surface. Rates of membrane uptake of benzanthracene from the crystalline, microcrystalline, and the silica-absorbed states were compared, and are greatly enhanced by a reduction in crystal size. Silica-adsorbed  benzanthracene had the most rapid rate of membrane uptake. Silica did not cause disruption of the lipid vesicles. These results indicate that particulates can enhance the cellular availability of the chemical carcinogens.", "contents": "Particulate enhanced membrane uptake of 1,2-benzanthracene observed by fluorescence spectroscopy: a possible role in co-carcinogenesis. In recognition of the co-carcinogenic effects of particulate matter and chemical carcinogens, we investigated the effect of particulate silica on the rates of membrane uptake of 1,2-benzanthracene. The fluorescence emission spectra and the apparent quantum yields of benzanthracene and dependent upon adsorption to silica and upon the surface density of benzanthracene on the silica. The fluorescence spectral shifts which occur upon transfer of benzanthracene from the silica surface to phospholipid vesicles provided a convenient means to quantitate the membrane uptake of benzanthracene from particulates. The rate of benzanthracene uptake by dipalmitoyl-L-alpha-phosphatidylcholine vesicles was independent of the concentration of lipid, indicating that the rate-limiting step may involve its solubilization in the aqueous phase. These uptake rates were also independent of the surface density of benzanthracene on the silica, indicating that the benzathracene molecules are dispersed uniformly on the silica surface. Rates of membrane uptake of benzanthracene from the crystalline, microcrystalline, and the silica-absorbed states were compared, and are greatly enhanced by a reduction in crystal size. Silica-adsorbed  benzanthracene had the most rapid rate of membrane uptake. Silica did not cause disruption of the lipid vesicles. These results indicate that particulates can enhance the cellular availability of the chemical carcinogens."}
{"id": "PMID:215223", "title": "On the question of cyclic GMP as the mediator of the effects of acetylcholine on the heart.", "content": "The effects of acetylcholine and sodium nitroprusside on cyclic GMP levels, contractile force, and glycogen metabolism were investigated in the perfused rat heart. While both agents produced time- and concentration-dependent increases in cyclic GMP, only acetylcholine significantly decreased contractile force. Neither agent altered the basal cyclic AMP concentration, cyclic AMP-dependent protein kinase activity ratio, or phosphorylase activity. When dosages were adjusted to give approximately equal increases in cyclic GMP, acetylcholine attenuated the effect of epinephrine on contractile force and glycogen phosphorylase activity while nitroprusside did not antagonize the action  of the beta-adrenergic agent on either parameter. The data suggest that increased cardiac cyclic GMP is not sufficient to completely explain the action of acetylcholine on either contractile force or its antagonism of epinephrine-induced increases in force or glycogen phosphorylase activity.", "contents": "On the question of cyclic GMP as the mediator of the effects of acetylcholine on the heart. The effects of acetylcholine and sodium nitroprusside on cyclic GMP levels, contractile force, and glycogen metabolism were investigated in the perfused rat heart. While both agents produced time- and concentration-dependent increases in cyclic GMP, only acetylcholine significantly decreased contractile force. Neither agent altered the basal cyclic AMP concentration, cyclic AMP-dependent protein kinase activity ratio, or phosphorylase activity. When dosages were adjusted to give approximately equal increases in cyclic GMP, acetylcholine attenuated the effect of epinephrine on contractile force and glycogen phosphorylase activity while nitroprusside did not antagonize the action  of the beta-adrenergic agent on either parameter. The data suggest that increased cardiac cyclic GMP is not sufficient to completely explain the action of acetylcholine on either contractile force or its antagonism of epinephrine-induced increases in force or glycogen phosphorylase activity."}
{"id": "PMID:215224", "title": "Properties of epinephrine-induced activation of cardiac adenosine 3',5'-monophosphate-dependent protein kinase.", "content": "The effects of epinephrine on cyclic AMP content and protein kinase activity were examined in an in situ rat heart preparation. Bolus injection of epinephrine into the superior vena cava caused an increase in the activity ratio (-cyclic AMP/\"cyclic AMP) of 12 000 X g supernatant protein kinase. The increase was significant within 5 s and maximal in 10 s. Epinephrine produced a dose-dependent increase in both protein kinase activity ratio and cyclic AMP content. The increases in both parameters exhibited a high degree of correlation. The increase in protein kinase activity ratio observed with low doses of epinephrine (less than or equal to 1 microgram/kg) resulted from an increase in independent protein kinase activity (-cyclic AMP) without a change in total protein kinase activity (+cyclic AMP). However, the increase in the activity ratio observed with higher doses of epinephrine (greater than 1 microgram/kg) was due mainly to a decrease in total protein kinase activity rather than a further increase in independent protein kinase activity. The loss of supernatant total protein kinase activity could be accounted for by an increase in activity associated with particulate fractions obtained from the homogenates. A similar redistribution of protein kinase could be demonstrated by the addition of cyclic AMP to homogenates prepared from hearts not stimulated with epinephrine. These results demonstrate that epinephrine over a wide dose range produces a parallel increase in the content of cyclic AMP and the activation of soluble protein kinase. The findings also suggest that protein kinase translocation to particulate material may depend on the degree of epinephrine-induced enzyme activation.", "contents": "Properties of epinephrine-induced activation of cardiac adenosine 3',5'-monophosphate-dependent protein kinase. The effects of epinephrine on cyclic AMP content and protein kinase activity were examined in an in situ rat heart preparation. Bolus injection of epinephrine into the superior vena cava caused an increase in the activity ratio (-cyclic AMP/\"cyclic AMP) of 12 000 X g supernatant protein kinase. The increase was significant within 5 s and maximal in 10 s. Epinephrine produced a dose-dependent increase in both protein kinase activity ratio and cyclic AMP content. The increases in both parameters exhibited a high degree of correlation. The increase in protein kinase activity ratio observed with low doses of epinephrine (less than or equal to 1 microgram/kg) resulted from an increase in independent protein kinase activity (-cyclic AMP) without a change in total protein kinase activity (+cyclic AMP). However, the increase in the activity ratio observed with higher doses of epinephrine (greater than 1 microgram/kg) was due mainly to a decrease in total protein kinase activity rather than a further increase in independent protein kinase activity. The loss of supernatant total protein kinase activity could be accounted for by an increase in activity associated with particulate fractions obtained from the homogenates. A similar redistribution of protein kinase could be demonstrated by the addition of cyclic AMP to homogenates prepared from hearts not stimulated with epinephrine. These results demonstrate that epinephrine over a wide dose range produces a parallel increase in the content of cyclic AMP and the activation of soluble protein kinase. The findings also suggest that protein kinase translocation to particulate material may depend on the degree of epinephrine-induced enzyme activation."}
{"id": "PMID:215225", "title": "Glucosyl transferase activity of bovine galactosyl transferase.", "content": "Bovine galactosyl transferase was found to utilize UDPglucose as a substrate and elicit disaccharide biosynthesis with glucose and N-acetylglucosamine as acceptors. The relative rate of glucosyl transferase with N-acetylglucosamine as acceptor was 0.3%, the rate for N-acetyllactosamine biosynthesis. This activity was also evidenced indirectly from NMR water proton relaxation experiments, and from Mn(II) ESR experiments. In direct experiments with radioactive UDPglucose, paper chromatography showed a product which migrated with cellobiose when glucose was the acceptor and a new, glucose-containing product which resulted when GlcNAc was the acceptor. Despite this marginally expanded specificity of the donor site, spin-label experiments with a covalently bound UDPgalactose analog reaffirmed the restrictive nature of the donor site against this non-glycosyl-like analog.", "contents": "Glucosyl transferase activity of bovine galactosyl transferase. Bovine galactosyl transferase was found to utilize UDPglucose as a substrate and elicit disaccharide biosynthesis with glucose and N-acetylglucosamine as acceptors. The relative rate of glucosyl transferase with N-acetylglucosamine as acceptor was 0.3%, the rate for N-acetyllactosamine biosynthesis. This activity was also evidenced indirectly from NMR water proton relaxation experiments, and from Mn(II) ESR experiments. In direct experiments with radioactive UDPglucose, paper chromatography showed a product which migrated with cellobiose when glucose was the acceptor and a new, glucose-containing product which resulted when GlcNAc was the acceptor. Despite this marginally expanded specificity of the donor site, spin-label experiments with a covalently bound UDPgalactose analog reaffirmed the restrictive nature of the donor site against this non-glycosyl-like analog."}
{"id": "PMID:215226", "title": "Modulation of platelet responsiveness through selective phosphorylation of plasma membrane proteins.", "content": "32P phosphorylation of plasma membranes from human blood platelets, under conditions that closely resemble physiological ones (endogeneous phosphate donors and intact platelets in homologous plasma), result in the incorporation of the label mainly in a membrane glycoprotein of apparently high molecular weight (greater than 400 000). Dibutyryl cyclic AMP, an inhibitor of platelet aggregation, specifically increases the degree of phosphorylation of this glycoprotein. Moreover, it has been found that prostaglandin E1 one of the most potent inhibitors of platelet aggregation which also increases phosphorylation of the same glycoprotein, is significantly more effective than cyclic AMP. Cyclic GMP does not have any apparent effect on platelet aggregation. However, incubation of platelet-rich plasma with both cyclic GMP and cyclic AMP results in a partial recovery of the platelet responsiveness towards ADP-induced aggregation. Coincidently, the degree of phosphorylation of the high molecular weight glycoprotein under these conditions, although still higher than in controls (no nucleotides added), is significantly decreased as compared with cyclic AMP-treated cells. Furthermore, cyclic GMP inhibits the cyclic AMP-dependent protein kinase activity in isolated platelet plasma membranes. These results suggest a central role for this membrane phosphoglycoprotein in the triggering of platelet aggregation and, furthermore, suggest that modulation of its degree of phosphorylation may be exerted through some cyclic AMP/cyclic GMP relationship, which in the basal state might be critical for platelet responsiveness.", "contents": "Modulation of platelet responsiveness through selective phosphorylation of plasma membrane proteins. 32P phosphorylation of plasma membranes from human blood platelets, under conditions that closely resemble physiological ones (endogeneous phosphate donors and intact platelets in homologous plasma), result in the incorporation of the label mainly in a membrane glycoprotein of apparently high molecular weight (greater than 400 000). Dibutyryl cyclic AMP, an inhibitor of platelet aggregation, specifically increases the degree of phosphorylation of this glycoprotein. Moreover, it has been found that prostaglandin E1 one of the most potent inhibitors of platelet aggregation which also increases phosphorylation of the same glycoprotein, is significantly more effective than cyclic AMP. Cyclic GMP does not have any apparent effect on platelet aggregation. However, incubation of platelet-rich plasma with both cyclic GMP and cyclic AMP results in a partial recovery of the platelet responsiveness towards ADP-induced aggregation. Coincidently, the degree of phosphorylation of the high molecular weight glycoprotein under these conditions, although still higher than in controls (no nucleotides added), is significantly decreased as compared with cyclic AMP-treated cells. Furthermore, cyclic GMP inhibits the cyclic AMP-dependent protein kinase activity in isolated platelet plasma membranes. These results suggest a central role for this membrane phosphoglycoprotein in the triggering of platelet aggregation and, furthermore, suggest that modulation of its degree of phosphorylation may be exerted through some cyclic AMP/cyclic GMP relationship, which in the basal state might be critical for platelet responsiveness."}
{"id": "PMID:215227", "title": "Regulation of the biosynthesis of cytochrome P-450 in brewer's yeast. Role of cyclic AMP.", "content": "The drug metabolising enzyme cytochrome P-450 has been studied in great detail in mammalian systems and its presence in microorganisms is also well established. However, neither its function nor its means of control in brewer's yeast, Saccharomyces cerevisiae, has been investigated. We demonstrate here using yeast protoplasts that it is the intracellular concentration of cyclic AMP which controls, by repression, the de novo synthesis of the enzyme, and also that cyclic AMP concentrations are in turn inversely related to the concentration of glucose in the yeast growth medium.", "contents": "Regulation of the biosynthesis of cytochrome P-450 in brewer's yeast. Role of cyclic AMP. The drug metabolising enzyme cytochrome P-450 has been studied in great detail in mammalian systems and its presence in microorganisms is also well established. However, neither its function nor its means of control in brewer's yeast, Saccharomyces cerevisiae, has been investigated. We demonstrate here using yeast protoplasts that it is the intracellular concentration of cyclic AMP which controls, by repression, the de novo synthesis of the enzyme, and also that cyclic AMP concentrations are in turn inversely related to the concentration of glucose in the yeast growth medium."}
{"id": "PMID:215228", "title": "ESR studies on the orientation of cholesteryl ester in phosphatidylcholine multilayers.", "content": "The alignment of cholesteryl esters in multilayer phosphatidylcholine membranes was investigated using two spin-labelled cholesteryl esters: 10 : 3 ester (I) and 1 : 14 ester (II). The nitroxide label of I is aligned in the membrane with a very large angle of tilt (47 degrees +/- 1.5 degrees) with respect to the normal to the membrane surface; II does not show such a tilt. I gives spectra corresponding to immobilized label while II gives nearly isotropic spectra. Ascorbate treatment of the multilayers shows that the labels in I and II are not present at the phosphatidylcholine-water interphase. The data supports a 'horseshoe' configuration for the cholesteryl ester in the bilayer, with both the fatty acid chain and the cholesteryl moiety extending deep into the hydrophobic region of the membrane and with the ester linkage near the surface.", "contents": "ESR studies on the orientation of cholesteryl ester in phosphatidylcholine multilayers. The alignment of cholesteryl esters in multilayer phosphatidylcholine membranes was investigated using two spin-labelled cholesteryl esters: 10 : 3 ester (I) and 1 : 14 ester (II). The nitroxide label of I is aligned in the membrane with a very large angle of tilt (47 degrees +/- 1.5 degrees) with respect to the normal to the membrane surface; II does not show such a tilt. I gives spectra corresponding to immobilized label while II gives nearly isotropic spectra. Ascorbate treatment of the multilayers shows that the labels in I and II are not present at the phosphatidylcholine-water interphase. The data supports a 'horseshoe' configuration for the cholesteryl ester in the bilayer, with both the fatty acid chain and the cholesteryl moiety extending deep into the hydrophobic region of the membrane and with the ester linkage near the surface."}
{"id": "PMID:215229", "title": "Labeling of human erythrocyte membranes with eosin probes used for protein diffusion measurements: inhibition of anion transport and photo-oxidative inactivation of acetylcholinesterase.", "content": "The binding of eosin-isothiocyanate (eosin-NCS) and iodoacetamido-eosin (IA-eosin) to band 3 proteins in the membrane of human erythrocytes is characterized by studying the effect of these probes on the anion transport system. Although the unbrominated fluorescein precursors do not affect anion transport, both eosin labels are strong inhibitors of sulphate exchange in intact erythrocytes. 50% inhibition is obtained by binding 4.7 . 10(5) or 6.0 . 10(5) molecules/cell for eosin-NCS and IA-eosin, respectively. Both eosin probes are irreversibly bound and occupy common binding sites with 4,4-diisothiocyano-1,2-diphenyl-ethane-2,2'disulfonic acid (H2DIDS), although other sites are labeled as well. The inhibition of anion transport is light independent and can therefore not be attributed to a photosensitizing action of the eosin probes. Both eosin derivatives, however, inactivate acetylcholinesterase upon illumination of air-equilibrated samples of hemoglobin-free labeled ghosts. The inactivation of the enzyme is accompanied by the formation of protein aggregates as visualized by polyacrylamide gel electrophoresis. These effects are not observed when intact erythrocytes are illuminated in the presence of eosin probes suggesting a protective effect of hemoglobin during the labeling procedure. Protection of ghosts from photo-oxidation is achieved by displacing air with argon. These results are discussed in relation to the use of these and similar probes to measure protein diffusion in membranes.", "contents": "Labeling of human erythrocyte membranes with eosin probes used for protein diffusion measurements: inhibition of anion transport and photo-oxidative inactivation of acetylcholinesterase. The binding of eosin-isothiocyanate (eosin-NCS) and iodoacetamido-eosin (IA-eosin) to band 3 proteins in the membrane of human erythrocytes is characterized by studying the effect of these probes on the anion transport system. Although the unbrominated fluorescein precursors do not affect anion transport, both eosin labels are strong inhibitors of sulphate exchange in intact erythrocytes. 50% inhibition is obtained by binding 4.7 . 10(5) or 6.0 . 10(5) molecules/cell for eosin-NCS and IA-eosin, respectively. Both eosin probes are irreversibly bound and occupy common binding sites with 4,4-diisothiocyano-1,2-diphenyl-ethane-2,2'disulfonic acid (H2DIDS), although other sites are labeled as well. The inhibition of anion transport is light independent and can therefore not be attributed to a photosensitizing action of the eosin probes. Both eosin derivatives, however, inactivate acetylcholinesterase upon illumination of air-equilibrated samples of hemoglobin-free labeled ghosts. The inactivation of the enzyme is accompanied by the formation of protein aggregates as visualized by polyacrylamide gel electrophoresis. These effects are not observed when intact erythrocytes are illuminated in the presence of eosin probes suggesting a protective effect of hemoglobin during the labeling procedure. Protection of ghosts from photo-oxidation is achieved by displacing air with argon. These results are discussed in relation to the use of these and similar probes to measure protein diffusion in membranes."}
{"id": "PMID:215230", "title": "Steady-state kinetics of formaldehyde dehydrogenase and formate dehydrogenase from a methanol-utilizing yeast, Candida boidinii.", "content": "Initial velocity studies and product inhibition studies were conducted for the forward and reverse reactions of formaldehyde dehydrogenase (formaldehyde: NAD oxidoreductase, EC 1.2.1.1) isolated from a methanol-utilizing yeast Candida boidinii. The data were consistent with an ordered Bi-Bi mechanism for this reaction in which NAD+ is bound first to the enzyme and NADH released last. Kinetic studies indicated that the nucleoside phosphates ATP, ADP and AMP are competitive inhibitors with respect to NAD and noncompetitive inhibitors with respect to S-hydroxymethylglutathione. The inhibitions of the enzyme activity by ATP and ADP are greater at pH 6.0 and 6.5 than at neutral or alkaline pH values. The kinetic studies of formate dehydrogenase (formate:NAD oxidoreductase, EC 1.2.1.2) from the methanol grown C. boidinii suggested also an ordered Bi-Bi mechanism with NAD being the first substrate and NADH the last product. Formate dehydrogenase the last enzyme of the dissimilatory pathway of the methanol metabolism is also inhibited by adenosine phosphates. Since the intracellular concentrations of NADH and ATP are in the range of the Ki values for formaldehyde dehydrogenase and formate dehydrogenase the activities of these main enzymes of the dissimilatory pathway of methanol metabolism in this yeast may be regulated by these compounds.", "contents": "Steady-state kinetics of formaldehyde dehydrogenase and formate dehydrogenase from a methanol-utilizing yeast, Candida boidinii. Initial velocity studies and product inhibition studies were conducted for the forward and reverse reactions of formaldehyde dehydrogenase (formaldehyde: NAD oxidoreductase, EC 1.2.1.1) isolated from a methanol-utilizing yeast Candida boidinii. The data were consistent with an ordered Bi-Bi mechanism for this reaction in which NAD+ is bound first to the enzyme and NADH released last. Kinetic studies indicated that the nucleoside phosphates ATP, ADP and AMP are competitive inhibitors with respect to NAD and noncompetitive inhibitors with respect to S-hydroxymethylglutathione. The inhibitions of the enzyme activity by ATP and ADP are greater at pH 6.0 and 6.5 than at neutral or alkaline pH values. The kinetic studies of formate dehydrogenase (formate:NAD oxidoreductase, EC 1.2.1.2) from the methanol grown C. boidinii suggested also an ordered Bi-Bi mechanism with NAD being the first substrate and NADH the last product. Formate dehydrogenase the last enzyme of the dissimilatory pathway of the methanol metabolism is also inhibited by adenosine phosphates. Since the intracellular concentrations of NADH and ATP are in the range of the Ki values for formaldehyde dehydrogenase and formate dehydrogenase the activities of these main enzymes of the dissimilatory pathway of methanol metabolism in this yeast may be regulated by these compounds."}
{"id": "PMID:215231", "title": "Peptide inhibitors of angiotensin I-converting enzyme in digests of gelatin by bacterial collagenase.", "content": "Peptide inhibitors of angiotensin I-converting enzyme (peptidyldipeptide hydrolase, EC 3.4.15.1) were produced by digesting gelatin with bacterial collagenase. The inhibitors were isolated from the digests with a combination of alcohol fractionation, treatment with Amberlite CG-50 column, gel filtration through Sephadex G-25, and Dowex 50 column and paper chromatography. Nine peptide fractions were purified to apparent homogeneity judging by thin-layer and ion-exchange column chromatography, and amino acid composition. Amino acid sequences of the peptides were determined: 2 were found to be mixtures of peptides and the sequence of another was only partially determined. Six of the peptides were potent inhibitors of the converting enzyme, while the other three were less active. 6 peptides were substrates for the enzyme. The enzyme released a dipeptide, Ala-Hyp from one peptide and was strongly inhibited by this dipeptide. The remainder of the parent peptides was a less effective inhibitor.", "contents": "Peptide inhibitors of angiotensin I-converting enzyme in digests of gelatin by bacterial collagenase. Peptide inhibitors of angiotensin I-converting enzyme (peptidyldipeptide hydrolase, EC 3.4.15.1) were produced by digesting gelatin with bacterial collagenase. The inhibitors were isolated from the digests with a combination of alcohol fractionation, treatment with Amberlite CG-50 column, gel filtration through Sephadex G-25, and Dowex 50 column and paper chromatography. Nine peptide fractions were purified to apparent homogeneity judging by thin-layer and ion-exchange column chromatography, and amino acid composition. Amino acid sequences of the peptides were determined: 2 were found to be mixtures of peptides and the sequence of another was only partially determined. Six of the peptides were potent inhibitors of the converting enzyme, while the other three were less active. 6 peptides were substrates for the enzyme. The enzyme released a dipeptide, Ala-Hyp from one peptide and was strongly inhibited by this dipeptide. The remainder of the parent peptides was a less effective inhibitor."}
{"id": "PMID:215232", "title": "Plasminogen activator from cells transformed by an oncogenic virus: inhibitors of the activation reaction.", "content": "This paper describes an assay for direct measurement of plasminogen activation and its application for determining the kinetic constants and for screening potential inhibitors of the reaction. The assay is based on the conversion of the single chain of 125I-labelled plasminogen to the two chains of 125I-labelled plasmin (EC 3.4.21.7), the latter then being separated from each other and from the plasminogen substrate by electrophoresis under reducing conditions in SDS-polyacrylamide gels. The Km of activator from transformed murine cells for human plasminogen was 180 nM. A broad range of compounds was tested as potential inhibitors of plasminogen activation and of plasmin-catalyzed fibrinolysis respectively, and the two reactions differed qualitatively and quantitatively in their response to previous agents. The principal qualitative difference was in the susceptibility of the reactions to a spectrum of naturally-occurring macromolecular inhibitors: all of the macromolecular inhibitors that blocked the action of plasmin were without effect on murine activator or human urokinase (EC 3.4.99.26). A variety of small molecules inhibited both of the reactions tested, and showed significant quantitative differences; some of these were active at micron concentrations. The exacting specificity of plasminogen activators for macromolecules, both substrates and inhibitors, encourages the expectation that effective inhibitors of great specificity may be isolated from as yet undiscovered natural sources.", "contents": "Plasminogen activator from cells transformed by an oncogenic virus: inhibitors of the activation reaction. This paper describes an assay for direct measurement of plasminogen activation and its application for determining the kinetic constants and for screening potential inhibitors of the reaction. The assay is based on the conversion of the single chain of 125I-labelled plasminogen to the two chains of 125I-labelled plasmin (EC 3.4.21.7), the latter then being separated from each other and from the plasminogen substrate by electrophoresis under reducing conditions in SDS-polyacrylamide gels. The Km of activator from transformed murine cells for human plasminogen was 180 nM. A broad range of compounds was tested as potential inhibitors of plasminogen activation and of plasmin-catalyzed fibrinolysis respectively, and the two reactions differed qualitatively and quantitatively in their response to previous agents. The principal qualitative difference was in the susceptibility of the reactions to a spectrum of naturally-occurring macromolecular inhibitors: all of the macromolecular inhibitors that blocked the action of plasmin were without effect on murine activator or human urokinase (EC 3.4.99.26). A variety of small molecules inhibited both of the reactions tested, and showed significant quantitative differences; some of these were active at micron concentrations. The exacting specificity of plasminogen activators for macromolecules, both substrates and inhibitors, encourages the expectation that effective inhibitors of great specificity may be isolated from as yet undiscovered natural sources."}
{"id": "PMID:215233", "title": "Purification and characterization of (Na+ + K+)-ATPase from toad kidney.", "content": "This report describes the partial purification and the characteristics of (Na+ + K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) from an amphibian source. Toad kidney microsomes were solubilized with sodium deoxycholate and further purified by sodium dodecyl sulphate treatment and sucrose gradient centrifugation, according to the methods described by Lane et al. [(1973) J. Biol. Chem. 248, 7197--7200], J\u00f8rgensen [(1974) Biochim. Biophys. Acta 356, 36--52] and Hayashi et al. [(1977) Biochim. Biophys. Acta 482, 185--196]. (Na+ + K+)-ATPase preparations with specific activities up to 1000 mumol Pi/mg protein per h were obtained. Mg2+-ATPase only accounted for about 2% of the total ATPase activity. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis revealed three major protein bands with molecular weights of 116 000, 62 000 and 26 000. The 116 000 dalton protein was phosphorylated by [gamma-32P]ATP in the presence of sodium but not in the presence of potassium. The 62 000 dalton component stained for glycoproteins. The Km for ATP was 0.40 mM, for Na+ 12.29 mM and for K+ 1.14 mM. The Ki for ouabain was 35 micron. Temperature activation curves showed two activity peaks at 37 degrees C and at 50 degrees C. The break in the Arrhenius plot of activity versus temperature appeared at 15 degrees C.", "contents": "Purification and characterization of (Na+ + K+)-ATPase from toad kidney. This report describes the partial purification and the characteristics of (Na+ + K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) from an amphibian source. Toad kidney microsomes were solubilized with sodium deoxycholate and further purified by sodium dodecyl sulphate treatment and sucrose gradient centrifugation, according to the methods described by Lane et al. [(1973) J. Biol. Chem. 248, 7197--7200], J\u00f8rgensen [(1974) Biochim. Biophys. Acta 356, 36--52] and Hayashi et al. [(1977) Biochim. Biophys. Acta 482, 185--196]. (Na+ + K+)-ATPase preparations with specific activities up to 1000 mumol Pi/mg protein per h were obtained. Mg2+-ATPase only accounted for about 2% of the total ATPase activity. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis revealed three major protein bands with molecular weights of 116 000, 62 000 and 26 000. The 116 000 dalton protein was phosphorylated by [gamma-32P]ATP in the presence of sodium but not in the presence of potassium. The 62 000 dalton component stained for glycoproteins. The Km for ATP was 0.40 mM, for Na+ 12.29 mM and for K+ 1.14 mM. The Ki for ouabain was 35 micron. Temperature activation curves showed two activity peaks at 37 degrees C and at 50 degrees C. The break in the Arrhenius plot of activity versus temperature appeared at 15 degrees C."}
{"id": "PMID:215234", "title": "Leukocyte migration inhibitory factor: a serine esterase released by stimulated human lymphocytes. Kinetic analysis and inhibition by cyclic GMP.", "content": "Lymphocytes, stimulated with concanavalin A, release small amounts of non-immunoglobulin, highly reactive proteins called lymphokines. One of these, a serine esterase, termed leukocyte migration inhibitory factor according to its function in vitro, is found in supernatants of stimulated human lymphocytes at concentrations less than 1 ng/ml. The esterase was purified in good yield and its esterolytic activity was measured by a sensitive radioenzymic assay. The kinetics of the esterolytic activity were studied and the effect of various nucleotides examined. Competitive inhibition of esterolysis was seen with cyclic GMP at concentrations down to 10(-7) M, and with 2',3'-cyclic CMP at a concentration of 10(-3) M. A role of this esterase, not only as a mediator acting upon polymorphonuclear leukocytes, but also as an intracellular regulator of lymphocyte activation, is discussed.", "contents": "Leukocyte migration inhibitory factor: a serine esterase released by stimulated human lymphocytes. Kinetic analysis and inhibition by cyclic GMP. Lymphocytes, stimulated with concanavalin A, release small amounts of non-immunoglobulin, highly reactive proteins called lymphokines. One of these, a serine esterase, termed leukocyte migration inhibitory factor according to its function in vitro, is found in supernatants of stimulated human lymphocytes at concentrations less than 1 ng/ml. The esterase was purified in good yield and its esterolytic activity was measured by a sensitive radioenzymic assay. The kinetics of the esterolytic activity were studied and the effect of various nucleotides examined. Competitive inhibition of esterolysis was seen with cyclic GMP at concentrations down to 10(-7) M, and with 2',3'-cyclic CMP at a concentration of 10(-3) M. A role of this esterase, not only as a mediator acting upon polymorphonuclear leukocytes, but also as an intracellular regulator of lymphocyte activation, is discussed."}
{"id": "PMID:215235", "title": "Ribonucleic acid synthesis in rat liver during fatty acid stimulated secretion of very low density lipoproteins.", "content": "Production of very low density lipoproteins by the liver depends on the cellular availability of fatty acids. It is stimulated by the uptake of free fatty acids from the plasma and by increased lipogenesis and is inhibited by actinomycin D, suggesting that RNA synthesis is involved in the regulation of apolipoprotein synthesis. This hypothesis has been investigated in rats in vivo and in isolated perfused livers with and without stimulation by fatty acid overload: [14C] orotate incorporation in liver polyribosomal RNA is 60 per cent greater in stimulated livers as compared to controls. This increase is primarily due to a higher incorporation in bound polysomes and in those containing at least six ribosomes and does not result from the inhibition of ribonuclease. RNase digestion of polysomal RNA (4.10(-10) M enzyme, 0 degrees C, 3 h) shows that there is twice as much radioactivity in the hydrolyzed RNA of stimulated livers as compared to controls. After partial purification of poly A-rich RNA by affinity chromatography, the mass yield and radioactivity are increased by 100 per cent in stimulated livers as compared to controls. In conclusion, de novo RNA synthesis seems to be necessary for fatty acid stimulation of VLDL production.", "contents": "Ribonucleic acid synthesis in rat liver during fatty acid stimulated secretion of very low density lipoproteins. Production of very low density lipoproteins by the liver depends on the cellular availability of fatty acids. It is stimulated by the uptake of free fatty acids from the plasma and by increased lipogenesis and is inhibited by actinomycin D, suggesting that RNA synthesis is involved in the regulation of apolipoprotein synthesis. This hypothesis has been investigated in rats in vivo and in isolated perfused livers with and without stimulation by fatty acid overload: [14C] orotate incorporation in liver polyribosomal RNA is 60 per cent greater in stimulated livers as compared to controls. This increase is primarily due to a higher incorporation in bound polysomes and in those containing at least six ribosomes and does not result from the inhibition of ribonuclease. RNase digestion of polysomal RNA (4.10(-10) M enzyme, 0 degrees C, 3 h) shows that there is twice as much radioactivity in the hydrolyzed RNA of stimulated livers as compared to controls. After partial purification of poly A-rich RNA by affinity chromatography, the mass yield and radioactivity are increased by 100 per cent in stimulated livers as compared to controls. In conclusion, de novo RNA synthesis seems to be necessary for fatty acid stimulation of VLDL production."}
{"id": "PMID:215236", "title": "[Quaternary structure and proteolysis of the polynucleotide phosphorylase from C. perfringens].", "content": "This report describes structural studies on purified polynucleotide phosphorylase from C. perfringens. A method is described for the purification of the enzyme which yields a product equivalent in activity to the native polynucleotide phosphorylase from E. coli. These studies revealed a molecular heterogeneity arising from successive stages of proteolysis, to which this enzyme is especially sensitive; unusally, the enzyme is obtained as a mixture of variable proportions of the native and proteolysed forms. We found in all cases a trimeric basic structure composed of the native (alpha) or proteolysed (lapha) or proteolysed (alpha', alpha\") catalytic sub-units, However, the enzyme is rather easily dissociated into its sub-units, a phenomenon which seems to accompany proteolysis (Table). Under the action of either endogenous proteases or trypsin, two enzymatic forms are obtained: their quaternary structures seem analogous, but they differ in their catalytic properties from each other and from the initial enzyme. With some care at each step of purification, the polynucleotide phosphorylase of E. coli can be obtained exclusively in its native form. The greater susceptibility to proteolysis of the enzyme from C. perfrigens and the relationship between such degradation and quaternary structure seem to be at the origin of the peculiar behavior of this polynucleotide phosphorylase.", "contents": "[Quaternary structure and proteolysis of the polynucleotide phosphorylase from C. perfringens]. This report describes structural studies on purified polynucleotide phosphorylase from C. perfringens. A method is described for the purification of the enzyme which yields a product equivalent in activity to the native polynucleotide phosphorylase from E. coli. These studies revealed a molecular heterogeneity arising from successive stages of proteolysis, to which this enzyme is especially sensitive; unusally, the enzyme is obtained as a mixture of variable proportions of the native and proteolysed forms. We found in all cases a trimeric basic structure composed of the native (alpha) or proteolysed (lapha) or proteolysed (alpha', alpha\") catalytic sub-units, However, the enzyme is rather easily dissociated into its sub-units, a phenomenon which seems to accompany proteolysis (Table). Under the action of either endogenous proteases or trypsin, two enzymatic forms are obtained: their quaternary structures seem analogous, but they differ in their catalytic properties from each other and from the initial enzyme. With some care at each step of purification, the polynucleotide phosphorylase of E. coli can be obtained exclusively in its native form. The greater susceptibility to proteolysis of the enzyme from C. perfrigens and the relationship between such degradation and quaternary structure seem to be at the origin of the peculiar behavior of this polynucleotide phosphorylase."}
{"id": "PMID:215237", "title": "Characterization of the cyclic AMP-dependent protein kinase from rat pancreas, further purification of the catalytic subunit, substrate specificity, effect of the pancreatic heat stable inhibitor.", "content": "In order to investigate the sequence of events triggered by cyclic AMP and cyclic GMP in exocrine pancreatic cells, the identification of the various protein kinases possibly present in this tissue is of major interest. Further analysis of the two cyclic AMP-dependent protein kinases previously reported [11] suggests that KI is a degraded form of KII. It is therefore likely that a single holoenzyme is present in exocrine cells. In addition no protein kinase, specifically stimulated by cyclic GMP, has been detected in any fraction obtained in the course of purification of the cyclic AMP-dependent protein kinase. A faster and more efficient method than the one previously described [11] allows the purification (5000 times) of the protein kinase catalytic subunit. Analysis of the subunit by sodium dodecyl sulphate polyacrylamide gel electrophoresis indicates a molecular weight of 40 000 +/- 1 000. The enzyme phosphorylates specifically histone H2B (Vm = 236 min(-1), Km = 1.15 10(-5) M) and to a lesser extent H2A, H5 and H1 (Vm = 55--77 min(-1), Km 5--25 10(-5) M). Histones H3 and H4 are not phosphorylated. The effect of the heat stable inhibitor, extracted from rat pancreas, on the phosphorylation of H2B has been investigated. The inhibition is of the non competitive type with respect to ATP. The inhibition at various histone concentrations cannot be described by the Michaelis-Menten equation.", "contents": "Characterization of the cyclic AMP-dependent protein kinase from rat pancreas, further purification of the catalytic subunit, substrate specificity, effect of the pancreatic heat stable inhibitor. In order to investigate the sequence of events triggered by cyclic AMP and cyclic GMP in exocrine pancreatic cells, the identification of the various protein kinases possibly present in this tissue is of major interest. Further analysis of the two cyclic AMP-dependent protein kinases previously reported [11] suggests that KI is a degraded form of KII. It is therefore likely that a single holoenzyme is present in exocrine cells. In addition no protein kinase, specifically stimulated by cyclic GMP, has been detected in any fraction obtained in the course of purification of the cyclic AMP-dependent protein kinase. A faster and more efficient method than the one previously described [11] allows the purification (5000 times) of the protein kinase catalytic subunit. Analysis of the subunit by sodium dodecyl sulphate polyacrylamide gel electrophoresis indicates a molecular weight of 40 000 +/- 1 000. The enzyme phosphorylates specifically histone H2B (Vm = 236 min(-1), Km = 1.15 10(-5) M) and to a lesser extent H2A, H5 and H1 (Vm = 55--77 min(-1), Km 5--25 10(-5) M). Histones H3 and H4 are not phosphorylated. The effect of the heat stable inhibitor, extracted from rat pancreas, on the phosphorylation of H2B has been investigated. The inhibition is of the non competitive type with respect to ATP. The inhibition at various histone concentrations cannot be described by the Michaelis-Menten equation."}
{"id": "PMID:215238", "title": "[In vitro comparative metabolism of 6,7-3H estrone and 6,7-3H estrone-3-sulfate in maternal and fetal guinea-pig liver].", "content": "The metabolism of [6,7-3H] estrone and of [6,7(3)H] estrone-3-sulfate have been comparatively studied in the maternal and fetal guinea-pig livers. The appearance of estradiol-17 beta resulting from the activity of the 17 beta-hydroxysteroid-dehydrogenase is more important in the fetal than in the maternal hepatic tissue. This suggests the direct transformation of estrone-3-sulfate into estradio-3-sulfate in the fetus. After incubation of the [3H] estrone, there is an abundant hepatic conjugation. The glycuroconjugated components are predominant, as well in the maternal as in the fetal hepatic tissue. For the latter-one the sulfoconjugation is inexistant. The sulfatasic activity shown after the incubation of [3H] estrone-3-sulfate is very low in the fetal hepatic tissue; in contrast, this activity is higher in the maternal tissue.", "contents": "[In vitro comparative metabolism of 6,7-3H estrone and 6,7-3H estrone-3-sulfate in maternal and fetal guinea-pig liver]. The metabolism of [6,7-3H] estrone and of [6,7(3)H] estrone-3-sulfate have been comparatively studied in the maternal and fetal guinea-pig livers. The appearance of estradiol-17 beta resulting from the activity of the 17 beta-hydroxysteroid-dehydrogenase is more important in the fetal than in the maternal hepatic tissue. This suggests the direct transformation of estrone-3-sulfate into estradio-3-sulfate in the fetus. After incubation of the [3H] estrone, there is an abundant hepatic conjugation. The glycuroconjugated components are predominant, as well in the maternal as in the fetal hepatic tissue. For the latter-one the sulfoconjugation is inexistant. The sulfatasic activity shown after the incubation of [3H] estrone-3-sulfate is very low in the fetal hepatic tissue; in contrast, this activity is higher in the maternal tissue."}
{"id": "PMID:215240", "title": "Large-scale rotational motions of proteins detected by electron paramagnetic resonance and fluorescence.", "content": "Direct spectroscopic measurements of rotational motions of proteins and large protein segments are crucial to understanding the molecular dynamics of protein function. Fluorescent probes and spin labels attached to proteins have proved to be powerful tools in the study of large-scale protein motions. Fluorescence depolarization and conventional electron paramagnetic resonance (EPR) are applicable to the study of rotational motions in the nanosecond-to-microsecond time range, and have been used to demonstrate segmental flexibility in an antibody and in myosin. Very slow rotational motions, occurring in the microsecond-to-millisecond time range, are particularly important in supramolecular assemblies, where protein motions are restricted by association with other molecules. Saturation transfer spectroscopy (ST-EPR), a recently developed electron paramagnetic resonance (EPR) technique that permits the detection of rotational correlation times as long as 1 ms, has been used to detect large-scale rotational motions of spin-labeled proteins in muscle filaments and in membranes, providing valuable insights into energy transduction mechanisms in these assemblies.", "contents": "Large-scale rotational motions of proteins detected by electron paramagnetic resonance and fluorescence. Direct spectroscopic measurements of rotational motions of proteins and large protein segments are crucial to understanding the molecular dynamics of protein function. Fluorescent probes and spin labels attached to proteins have proved to be powerful tools in the study of large-scale protein motions. Fluorescence depolarization and conventional electron paramagnetic resonance (EPR) are applicable to the study of rotational motions in the nanosecond-to-microsecond time range, and have been used to demonstrate segmental flexibility in an antibody and in myosin. Very slow rotational motions, occurring in the microsecond-to-millisecond time range, are particularly important in supramolecular assemblies, where protein motions are restricted by association with other molecules. Saturation transfer spectroscopy (ST-EPR), a recently developed electron paramagnetic resonance (EPR) technique that permits the detection of rotational correlation times as long as 1 ms, has been used to detect large-scale rotational motions of spin-labeled proteins in muscle filaments and in membranes, providing valuable insights into energy transduction mechanisms in these assemblies."}
{"id": "PMID:215241", "title": "Spin label detection of intermolecular interactions in carbonmonoxy sickle hemoglobin.", "content": "With recently developed spin label techniques for monitoring macromolecular rotational motion, heme-liganded sickle cell hemoglobin in the presence of inositol hexaphosphate is shown to exhibit restricted motional freedom as compared to liganded normal adult human hemoglobin. This motional restriction is dependent on both hemoglobin concentration and temperature.", "contents": "Spin label detection of intermolecular interactions in carbonmonoxy sickle hemoglobin. With recently developed spin label techniques for monitoring macromolecular rotational motion, heme-liganded sickle cell hemoglobin in the presence of inositol hexaphosphate is shown to exhibit restricted motional freedom as compared to liganded normal adult human hemoglobin. This motional restriction is dependent on both hemoglobin concentration and temperature."}
{"id": "PMID:215245", "title": "[Effect of potassium iodide and perchlorate on the process of thyroid hormone secretion].", "content": "The influence of potassium iodide and perchlorate on the parameters characterizing the thypoid hormones secretion, such as the cAMP level in the gland tissue and the number of intracellular colloid droplets under condition of stimulation by thyrotropic hormone was studied. It was shown that the abovementioned parameters were depressed by an excess of iodide, but perchlorate administration prevented the inhibitory effect of iodide. The results obtained favour the conception on the sensitivity of the thyroid adenylate cyclase system to the organic iodine concentration. Apparently and excess of iodide depressed the capacity of perchlorate to influence its concentration in the gland, and thereby the process of iodine organification and of the thyroid hormone secretion maintained at the optimal leve.", "contents": "[Effect of potassium iodide and perchlorate on the process of thyroid hormone secretion]. The influence of potassium iodide and perchlorate on the parameters characterizing the thypoid hormones secretion, such as the cAMP level in the gland tissue and the number of intracellular colloid droplets under condition of stimulation by thyrotropic hormone was studied. It was shown that the abovementioned parameters were depressed by an excess of iodide, but perchlorate administration prevented the inhibitory effect of iodide. The results obtained favour the conception on the sensitivity of the thyroid adenylate cyclase system to the organic iodine concentration. Apparently and excess of iodide depressed the capacity of perchlorate to influence its concentration in the gland, and thereby the process of iodine organification and of the thyroid hormone secretion maintained at the optimal leve."}
{"id": "PMID:215246", "title": "[Effect of gangliosides on Na-K-ATPase activity and the conformation of microsomal membranes].", "content": "The effect of gangliosides on the activity of Na, K-ATPase and K-dependent nitrophenyl-phosphatase was studied. Low concentrations of gangliosides proved to activate Na, K-ATPase, and high ones to inhibit it. All the concentrations of gangliosides produced only an inhibitory effect on the K-dependent nitrophenyl-phosphatase. Inhibition of the enzyme by gangliosides is reversible and competitive in respect to K+. Calculation of Hill's coefficient demonstrated that both in case of the activating and of the inhibitory action gangliosides acted allosteric effectors. To ascertain the action mechanism of gangliosides on the enzyme their effect on the microsomal membranes was studied by the fluorescent probe method. Gangliosides were found to produce marked conformation shifts in the membranes of the brain microsomes.", "contents": "[Effect of gangliosides on Na-K-ATPase activity and the conformation of microsomal membranes]. The effect of gangliosides on the activity of Na, K-ATPase and K-dependent nitrophenyl-phosphatase was studied. Low concentrations of gangliosides proved to activate Na, K-ATPase, and high ones to inhibit it. All the concentrations of gangliosides produced only an inhibitory effect on the K-dependent nitrophenyl-phosphatase. Inhibition of the enzyme by gangliosides is reversible and competitive in respect to K+. Calculation of Hill's coefficient demonstrated that both in case of the activating and of the inhibitory action gangliosides acted allosteric effectors. To ascertain the action mechanism of gangliosides on the enzyme their effect on the microsomal membranes was studied by the fluorescent probe method. Gangliosides were found to produce marked conformation shifts in the membranes of the brain microsomes."}
{"id": "PMID:215247", "title": "[Alterations of Rous virus and polyoma virus during their synthesis in the cells of unnatural hosts].", "content": "The line of human embryo fibroblasts transformed by Rous sarcoma virus (strain Schmidt-Ruppin) contained and produced Rous sarcoma virus; this was shown by the complement fixation test, immunofluorescent test, electron microscopy and labelling with 3H-uridine peak in sucrose gradient. Biological properties of the new synthesized virus differed from that of the parent Schmidt-Ruppin strain; the range of the sensitive cells and the protein envelope antigens altered in particular. Analogous results by the change of the viral biological properties produced in the unnatural host tissue were obtained for polioma virus synthesized in the human embryo fibroblasts transformed by this virus.", "contents": "[Alterations of Rous virus and polyoma virus during their synthesis in the cells of unnatural hosts]. The line of human embryo fibroblasts transformed by Rous sarcoma virus (strain Schmidt-Ruppin) contained and produced Rous sarcoma virus; this was shown by the complement fixation test, immunofluorescent test, electron microscopy and labelling with 3H-uridine peak in sucrose gradient. Biological properties of the new synthesized virus differed from that of the parent Schmidt-Ruppin strain; the range of the sensitive cells and the protein envelope antigens altered in particular. Analogous results by the change of the viral biological properties produced in the unnatural host tissue were obtained for polioma virus synthesized in the human embryo fibroblasts transformed by this virus."}
{"id": "PMID:215248", "title": "Direct characterization of beta-adrenoceptors in membranes of immature red blood cells from rats.", "content": "By means of the radioactive antagonist ligand (3H)(-) dihydroalprenolol (DHAP) specific binding sites were identified in membrane preparations from red blood cells from rats. These specific sites were characterized as beta-adrenoceptors because of the following reasons: Specific binding of DHAP (in contrast to unspecific binding) was dependent on temperature and time of incubation. Furthermore, specific binding of DHAP showed saturability, temperature-dependent reversibility and high affinity (KD-value of DHAP = 6.51 nM). Specific binding of DHAP was competitively inhibited by beta-adrenergic antagonists (pindolol greater than alprenolol greater than or equal to propranolol greater than practolol) and agonists (isoprenaline greater than adrenaline). The (-) enantiomers of pindolol and isoprenaline showed pronounced higher affinities for the receptor sites than the respective (+) enantiomers. The receptor density in the membrane preparations (pmoles/mg protein) was strongly dependent on the degree of reticulocytosis: The Bmax-values increased more than 4 to 5 fold without alteration of the respective KD-values when reticulocyte counts were enhanced from 3 to 80% treatment of the animals with increasing doses of acetyl phenylhydrazine.", "contents": "Direct characterization of beta-adrenoceptors in membranes of immature red blood cells from rats. By means of the radioactive antagonist ligand (3H)(-) dihydroalprenolol (DHAP) specific binding sites were identified in membrane preparations from red blood cells from rats. These specific sites were characterized as beta-adrenoceptors because of the following reasons: Specific binding of DHAP (in contrast to unspecific binding) was dependent on temperature and time of incubation. Furthermore, specific binding of DHAP showed saturability, temperature-dependent reversibility and high affinity (KD-value of DHAP = 6.51 nM). Specific binding of DHAP was competitively inhibited by beta-adrenergic antagonists (pindolol greater than alprenolol greater than or equal to propranolol greater than practolol) and agonists (isoprenaline greater than adrenaline). The (-) enantiomers of pindolol and isoprenaline showed pronounced higher affinities for the receptor sites than the respective (+) enantiomers. The receptor density in the membrane preparations (pmoles/mg protein) was strongly dependent on the degree of reticulocytosis: The Bmax-values increased more than 4 to 5 fold without alteration of the respective KD-values when reticulocyte counts were enhanced from 3 to 80% treatment of the animals with increasing doses of acetyl phenylhydrazine."}
{"id": "PMID:215257", "title": "A comparison of myelopathy associated with megavoltage irradiation and remote cancer.", "content": "Two middle-aged women with malignancy of the aerodigestive tract were treated by megavoltage irradiation. Both subsequently developed transverse myelopathy. The diagnosis of radiation myelitis was rendered in one. The other was thought to have metastatic compression of the spinal cord; in this case, evidence was such that radiation myelopathy also was appropriate. The irradiation dose-time relationships in both patients were biologically low compared to published isoeffect curves available in the literature. The first patient had injury within the irradiated region and the main neurological damage was found there. In the second patient the entire spinal cord was necrotic, clearly placing the second case outside the radiation myelopathy syndrome. Gross and microscopic examinations of the tissues of these two patients show that the remote effects of malignancy upon the central nervous system can imitate the clinical picture of radiation myelitis.", "contents": "A comparison of myelopathy associated with megavoltage irradiation and remote cancer. Two middle-aged women with malignancy of the aerodigestive tract were treated by megavoltage irradiation. Both subsequently developed transverse myelopathy. The diagnosis of radiation myelitis was rendered in one. The other was thought to have metastatic compression of the spinal cord; in this case, evidence was such that radiation myelopathy also was appropriate. The irradiation dose-time relationships in both patients were biologically low compared to published isoeffect curves available in the literature. The first patient had injury within the irradiated region and the main neurological damage was found there. In the second patient the entire spinal cord was necrotic, clearly placing the second case outside the radiation myelopathy syndrome. Gross and microscopic examinations of the tissues of these two patients show that the remote effects of malignancy upon the central nervous system can imitate the clinical picture of radiation myelitis."}
{"id": "PMID:215258", "title": "Evaluation of follow-up services for elderly people prescribed hearing aids: report of a pilot project.", "content": "The first stage of a programme to determine the effectiveness of different types of follow-up service for elderly people prescribed hearing aids is described. Follow-up sessions of two hours each were held at fortnightly intervals and were given to groups comprising six patients. Three treatments were compared, one consisting of two follow-up sessions, the second of four sessions, and the third none (the control group). Two groups received each treatment. The results failed to demonstrate any advantage from the treatments. The men, who were more handicapped by their hearing loss, did better than women and there was a predominance of men in the control groups. The necessity of some follow-up service was demonstrated since a substantial proportion of patients were not utilising their aids satisfactorily at six months after issue and had problems which were then resolved. Any follow-up programme must concentrate very heavily on basic handling and maintenance of the aid, for most of the difficulties experienced were with these.", "contents": "Evaluation of follow-up services for elderly people prescribed hearing aids: report of a pilot project. The first stage of a programme to determine the effectiveness of different types of follow-up service for elderly people prescribed hearing aids is described. Follow-up sessions of two hours each were held at fortnightly intervals and were given to groups comprising six patients. Three treatments were compared, one consisting of two follow-up sessions, the second of four sessions, and the third none (the control group). Two groups received each treatment. The results failed to demonstrate any advantage from the treatments. The men, who were more handicapped by their hearing loss, did better than women and there was a predominance of men in the control groups. The necessity of some follow-up service was demonstrated since a substantial proportion of patients were not utilising their aids satisfactorily at six months after issue and had problems which were then resolved. Any follow-up programme must concentrate very heavily on basic handling and maintenance of the aid, for most of the difficulties experienced were with these."}
{"id": "PMID:215259", "title": "[The mechanism of gonadal differentiation].", "content": "The steroid-hormone dependent sexual development presupposes the already sex-specific differentiated gonads. The H-Y antigen is held responsible for the primary differentiation of the indifferent gonadal anlage towards testicular organization. Studies on the function of H-Y antigen, using gonadal cells in vitro, have shown that in the presence of H-Y antigen the gonad differentiates into testicular, in its absence into ovarian structures, independent of whether the sex chromosomes are XX or XY. The gonads of both sexes are endowed with a specific H-Y receptor, other tissues are not. The bipotency of the gonadal anlage arises from this character. Some disorders of sexual development presumably go back to mutations affecting the genetic control of the H-Y gene and the function of H-Y antigen, respectively. It is discussed that the Y chromosome may have a mere regulatory function and not include the H-Y gene. Thus, the primary differentiation of the gonad should be dependent exclusively on whether or not the H-Y gene is active.", "contents": "[The mechanism of gonadal differentiation]. The steroid-hormone dependent sexual development presupposes the already sex-specific differentiated gonads. The H-Y antigen is held responsible for the primary differentiation of the indifferent gonadal anlage towards testicular organization. Studies on the function of H-Y antigen, using gonadal cells in vitro, have shown that in the presence of H-Y antigen the gonad differentiates into testicular, in its absence into ovarian structures, independent of whether the sex chromosomes are XX or XY. The gonads of both sexes are endowed with a specific H-Y receptor, other tissues are not. The bipotency of the gonadal anlage arises from this character. Some disorders of sexual development presumably go back to mutations affecting the genetic control of the H-Y gene and the function of H-Y antigen, respectively. It is discussed that the Y chromosome may have a mere regulatory function and not include the H-Y gene. Thus, the primary differentiation of the gonad should be dependent exclusively on whether or not the H-Y gene is active."}
{"id": "PMID:215260", "title": "Modulation of noradrenergic transmission in the rabbit ear artery by dopamine.", "content": "1. The effects of dopamine on vasoconstrictor responses to field stimulation of sympathetic nerves and to exogenous noradrenaline were studied in the isolated ear artery of the rabbit. Responses to noradrenaline were unchanged at the start of the dopamine infusions but were enhanced as the infusions continued and also after cessation of the infustion. 2 Dopamine (0.5 muM) reduced the stimulation-induced efflux of tritium from segments of ear artery labelled with [3H]-noradrenaline. The reduction persisted during 65 min of dopamine infusion, after which time the vasoconstrictor responses had generally recovered to 93% of control level. On ceasing the infusion, the stimulation-induced efflux and the vasoconstrictor responses were enhanced. 3 Metoclopramide, haloperidol and ergometrine, each in a concentration of 0.2 muM, prevented the inhibitory effect of 0.5 muM dopamine on the stimulation-induced tritium release, but not the inhibitory effect of 0.5 muM noradrenaline. Phenoxybenzamine (0.2 and 1 muM) and phentolamine (1 muM) prevented the inhibitory effects of both noradrenaline and dopamine on the stimulation-induced efflux, and phentolamine (0.2 muM) prevented the inhibition of the stimulation-induced release by noradrenaline but only partially prevented the inhibitory effect of dopamine on the stimulation-induced efflux. 4 A possible role for dopamine in the modulation of noradrenergic transmission is suggested.", "contents": "Modulation of noradrenergic transmission in the rabbit ear artery by dopamine. 1. The effects of dopamine on vasoconstrictor responses to field stimulation of sympathetic nerves and to exogenous noradrenaline were studied in the isolated ear artery of the rabbit. Responses to noradrenaline were unchanged at the start of the dopamine infusions but were enhanced as the infusions continued and also after cessation of the infustion. 2 Dopamine (0.5 muM) reduced the stimulation-induced efflux of tritium from segments of ear artery labelled with [3H]-noradrenaline. The reduction persisted during 65 min of dopamine infusion, after which time the vasoconstrictor responses had generally recovered to 93% of control level. On ceasing the infusion, the stimulation-induced efflux and the vasoconstrictor responses were enhanced. 3 Metoclopramide, haloperidol and ergometrine, each in a concentration of 0.2 muM, prevented the inhibitory effect of 0.5 muM dopamine on the stimulation-induced tritium release, but not the inhibitory effect of 0.5 muM noradrenaline. Phenoxybenzamine (0.2 and 1 muM) and phentolamine (1 muM) prevented the inhibitory effects of both noradrenaline and dopamine on the stimulation-induced efflux, and phentolamine (0.2 muM) prevented the inhibition of the stimulation-induced release by noradrenaline but only partially prevented the inhibitory effect of dopamine on the stimulation-induced efflux. 4 A possible role for dopamine in the modulation of noradrenergic transmission is suggested."}
{"id": "PMID:215261", "title": "Mechanisms of inactivation of noradrenaline in the iris sphincter, tracheal muscle and facial artery of cattle: implications for beta-adrenoceptor-mediated responses.", "content": "1 The role of neuronal and extraneuronal pathways of amine inactivation in regulating the inhibitory actions of noradrenaline was investigated in three bovine smooth muscle preparations in which the primary adrenoceptor is of the beta-type.2 The extraneuronal uptake inhibitor, 17beta-oestradiol, sensitized the inhibitory responses to noradrenaline in the facial artery, the iris sphincter and in tracheal muscle preparations, indicating a major role for non-neuronal processes in agonist-inactivation in all three preparations. Cocaine also increased responses to noradrenaline, pointing to a role for neuronal uptake either as a terminating mechanism or as a process limiting access of exogenous agonist molecules to their site of action.3 Cocaine did not enhance significantly responses to isoprenaline, a potent beta-adrenoceptor agonist which is not taken up neuronally. Further, relaxations to metaraminol, a sympathomimetic amine which is taken up extraneuronally, but much less so than noradrenaline, were also less enhanced by 17beta-oestradiol in the three preparations tested. These findings support the specificity of action of cocaine and 17beta-oestradiol as neuronal and extraneuronal uptake inhibitors in the present experiments.4 Studies of the uptake of [(3)H]-noradrenaline revealed that 17beta-oestradiol reduced the uptake of amine in the presence of cocaine, confirming a cocaine-resistant site of action for the steroid in all three preparations.5 It is concluded that extraneuronal uptake sites are located sufficiently close to the beta-adrenoceptors to modulate the concentration and duration of action of noradrenaline at these sites of action. It is proposed that in smooth muscles which contain a preponderance of beta-receptors, extraneuronal metabolism is a key event in terminating the inhibitory effects produced.", "contents": "Mechanisms of inactivation of noradrenaline in the iris sphincter, tracheal muscle and facial artery of cattle: implications for beta-adrenoceptor-mediated responses. 1 The role of neuronal and extraneuronal pathways of amine inactivation in regulating the inhibitory actions of noradrenaline was investigated in three bovine smooth muscle preparations in which the primary adrenoceptor is of the beta-type.2 The extraneuronal uptake inhibitor, 17beta-oestradiol, sensitized the inhibitory responses to noradrenaline in the facial artery, the iris sphincter and in tracheal muscle preparations, indicating a major role for non-neuronal processes in agonist-inactivation in all three preparations. Cocaine also increased responses to noradrenaline, pointing to a role for neuronal uptake either as a terminating mechanism or as a process limiting access of exogenous agonist molecules to their site of action.3 Cocaine did not enhance significantly responses to isoprenaline, a potent beta-adrenoceptor agonist which is not taken up neuronally. Further, relaxations to metaraminol, a sympathomimetic amine which is taken up extraneuronally, but much less so than noradrenaline, were also less enhanced by 17beta-oestradiol in the three preparations tested. These findings support the specificity of action of cocaine and 17beta-oestradiol as neuronal and extraneuronal uptake inhibitors in the present experiments.4 Studies of the uptake of [(3)H]-noradrenaline revealed that 17beta-oestradiol reduced the uptake of amine in the presence of cocaine, confirming a cocaine-resistant site of action for the steroid in all three preparations.5 It is concluded that extraneuronal uptake sites are located sufficiently close to the beta-adrenoceptors to modulate the concentration and duration of action of noradrenaline at these sites of action. It is proposed that in smooth muscles which contain a preponderance of beta-receptors, extraneuronal metabolism is a key event in terminating the inhibitory effects produced."}
{"id": "PMID:215262", "title": "Comparison of the receptor binding characteristics of opiate agonists interacting with mu- or kappa-receptors.", "content": "1 The receptor binding characteristics of various morphine-like and ketazocine-like opiate agonists were measured by inhibition of [3H]-naloxone binding in homogenates of brain and of ileal myenteric plexus-longitudinal muscle of the guinea-pig. No differences were found for the two tissues. 2 The depressant effect of Na+ on the inhibition of [3H]-naloxone binding by opiate agonists varies widely, giving sodium shifts between 5 and 140. The relationship between Na+ concentration and inhibition of binding is non-linear, the magnitude of the sodium shift varying directly with the slope of the regression of log IC50 on log [NaCl]. 3 The sodium shift of ketazocine-like agonists is lower than that of morphine-like agonists but higher than that of opiates with dual agonist and antagonist action. A working hypothesis is proposed which suggests that the kappa-receptors for the ketazocine-like drugs are less susceptible to the Na+ effect than the mu-receptors for the morphine-like drugs. 4 For most of the morphine-like but not the ketazocine-like agonists, a good correlation has been found for the pharmacological activity in the myenteric plexus-longitudinal muscle preparation and the inhibition of binding of [3H]-naloxone at 12 mM Na+. An exception is fentanyl which has a much greater pharmacological potency than may be expected from its potency in inhibiting [3H]-naloxone binding.", "contents": "Comparison of the receptor binding characteristics of opiate agonists interacting with mu- or kappa-receptors. 1 The receptor binding characteristics of various morphine-like and ketazocine-like opiate agonists were measured by inhibition of [3H]-naloxone binding in homogenates of brain and of ileal myenteric plexus-longitudinal muscle of the guinea-pig. No differences were found for the two tissues. 2 The depressant effect of Na+ on the inhibition of [3H]-naloxone binding by opiate agonists varies widely, giving sodium shifts between 5 and 140. The relationship between Na+ concentration and inhibition of binding is non-linear, the magnitude of the sodium shift varying directly with the slope of the regression of log IC50 on log [NaCl]. 3 The sodium shift of ketazocine-like agonists is lower than that of morphine-like agonists but higher than that of opiates with dual agonist and antagonist action. A working hypothesis is proposed which suggests that the kappa-receptors for the ketazocine-like drugs are less susceptible to the Na+ effect than the mu-receptors for the morphine-like drugs. 4 For most of the morphine-like but not the ketazocine-like agonists, a good correlation has been found for the pharmacological activity in the myenteric plexus-longitudinal muscle preparation and the inhibition of binding of [3H]-naloxone at 12 mM Na+. An exception is fentanyl which has a much greater pharmacological potency than may be expected from its potency in inhibiting [3H]-naloxone binding."}
{"id": "PMID:215264", "title": "Stimulation of non-neuronal cell proliferation in vitro by mitogenic factors present in highly purified sympathetic neurons.", "content": "Sympathetic neurons have been demonstrated to contain one or more mitogens which are active on highly purified non-neuronal cells cultured in medium containing an optimal concentration of fetal calf serum. Neurons and homologous non-neuronal cells were separated by a method recently developed in this laboratory. The highly purified neurons were either sonicated or homogenized prior to addition to nonneuronal cultures. The presence of neuronal sonicate (1) greatly stimulated [3H]thymidine incorporation into acid-precipitable macromolecules without altering the soluble [3H]thymidine pool, (2) increased both the fraction of non-neuronal cells which took up [3H]thymidine and the density of labeling as observed by autoradiography, and (3) increased the number of cells present in treated cultures after 40 h. The enhancement of [3H]thymidine incorporation was dose-dependent and did not involve cyclic AMP. Addition of neuronal sonicate also caused marked non-neuronal cell elongation which resulted in the elaboration of very long cell processes. The active factor(s) in the neuronal sonicate were partially heat-labile. Norepinephrine was ruled out as a possible mitogenic factor.", "contents": "Stimulation of non-neuronal cell proliferation in vitro by mitogenic factors present in highly purified sympathetic neurons. Sympathetic neurons have been demonstrated to contain one or more mitogens which are active on highly purified non-neuronal cells cultured in medium containing an optimal concentration of fetal calf serum. Neurons and homologous non-neuronal cells were separated by a method recently developed in this laboratory. The highly purified neurons were either sonicated or homogenized prior to addition to nonneuronal cultures. The presence of neuronal sonicate (1) greatly stimulated [3H]thymidine incorporation into acid-precipitable macromolecules without altering the soluble [3H]thymidine pool, (2) increased both the fraction of non-neuronal cells which took up [3H]thymidine and the density of labeling as observed by autoradiography, and (3) increased the number of cells present in treated cultures after 40 h. The enhancement of [3H]thymidine incorporation was dose-dependent and did not involve cyclic AMP. Addition of neuronal sonicate also caused marked non-neuronal cell elongation which resulted in the elaboration of very long cell processes. The active factor(s) in the neuronal sonicate were partially heat-labile. Norepinephrine was ruled out as a possible mitogenic factor."}
{"id": "PMID:215266", "title": "Inhibitory and excitatory binocular convergence to visual cortical neurons of the cat.", "content": "Responses of 182 visual cortical (VC) neurons to electrical stimulation of both optic nerves (ON) were recorded intra- and extracellularly, and their eye dominance determined with visual stimuli. Many VC neurons could not be excited by ON stimulation without simultaneous activation by visual stimulation of the eye of the other side. The ON-excited units (25 simple and 71 complex cells) had essentially the same response latency from both ONs. In almost all VC neurons including those not driven from the ON, ON stimulation elicited inhibition which was shown to be post-synaptic in all neurons recorded intra- or quasi-intracellularly. The onset latency of IPSPs not preceded by an action potential or EPSP was 4.2+/-1.0 msec, suggesting that intracortical inhibition was initiated by afferent impulses mediated through fast conducting fibers. In visually monocular neurons, ON stimulation of the non-driving side also elicited primary inhibition. Visually binocular, but monocular-dominant neurons responded more reliably to ON stimulation of the dominant side than to the other. In most binocular neurons with equal visual responsiveness to both eyes, inhibition and excitation evoked from both ONs had about the same latency and magnitude.", "contents": "Inhibitory and excitatory binocular convergence to visual cortical neurons of the cat. Responses of 182 visual cortical (VC) neurons to electrical stimulation of both optic nerves (ON) were recorded intra- and extracellularly, and their eye dominance determined with visual stimuli. Many VC neurons could not be excited by ON stimulation without simultaneous activation by visual stimulation of the eye of the other side. The ON-excited units (25 simple and 71 complex cells) had essentially the same response latency from both ONs. In almost all VC neurons including those not driven from the ON, ON stimulation elicited inhibition which was shown to be post-synaptic in all neurons recorded intra- or quasi-intracellularly. The onset latency of IPSPs not preceded by an action potential or EPSP was 4.2+/-1.0 msec, suggesting that intracortical inhibition was initiated by afferent impulses mediated through fast conducting fibers. In visually monocular neurons, ON stimulation of the non-driving side also elicited primary inhibition. Visually binocular, but monocular-dominant neurons responded more reliably to ON stimulation of the dominant side than to the other. In most binocular neurons with equal visual responsiveness to both eyes, inhibition and excitation evoked from both ONs had about the same latency and magnitude."}
{"id": "PMID:215267", "title": "The neuronal pathway subserving the pupillary light reflex.", "content": "The pupillary light reflex was investigated using electrical stimulation along the pathway and recording in the short ciliary nerves. The discharge of single units in the ciliary ganglion was compared during diffuse light stimuli and electrical stimuli. It was concluded that the early reflex discharge in the short ciliary nerves following electrical stimulation on the optic tract is due to excitation of fibres active during the pupillary light reflex. The light reflex is conveyed by slow (less than 10 m/sec) optic tract fibres which synapase in the medial part of the pretectal area. In turn, pretectal neurones with conduction velocities of about 6 m/sec pass to the Edinger-Westphal complex from which the preganglionic 'pupilloconstrictor' neurones originate. Latency measurements show that there are synapses in the pretectal region and the Edinger-Westphal nucleus. The amplitude of the 'pupilloconstrictor' responses in the short ciliary nerves can be used as a measure of the excitability in the pathway of the pupillary light reflex under various conditions, e.g. following conditioning stimuli of other interacting pathways. In addition to the 'pupilloconstrictor' response there is also another short-latency discharge in the short ciliary nerves following stimulation of the posterior commissure and the Edinger-Westphal nucleus. That discharge is presumably due to activation of fibres which cause accommodation of the lens.", "contents": "The neuronal pathway subserving the pupillary light reflex. The pupillary light reflex was investigated using electrical stimulation along the pathway and recording in the short ciliary nerves. The discharge of single units in the ciliary ganglion was compared during diffuse light stimuli and electrical stimuli. It was concluded that the early reflex discharge in the short ciliary nerves following electrical stimulation on the optic tract is due to excitation of fibres active during the pupillary light reflex. The light reflex is conveyed by slow (less than 10 m/sec) optic tract fibres which synapase in the medial part of the pretectal area. In turn, pretectal neurones with conduction velocities of about 6 m/sec pass to the Edinger-Westphal complex from which the preganglionic 'pupilloconstrictor' neurones originate. Latency measurements show that there are synapses in the pretectal region and the Edinger-Westphal nucleus. The amplitude of the 'pupilloconstrictor' responses in the short ciliary nerves can be used as a measure of the excitability in the pathway of the pupillary light reflex under various conditions, e.g. following conditioning stimuli of other interacting pathways. In addition to the 'pupilloconstrictor' response there is also another short-latency discharge in the short ciliary nerves following stimulation of the posterior commissure and the Edinger-Westphal nucleus. That discharge is presumably due to activation of fibres which cause accommodation of the lens."}
{"id": "PMID:215268", "title": "Cerebellar influence on parasympathetic neurones innervating intra-ocular muscles.", "content": "Previous work has suggested that cerebellum may control the size of the pupil and transmission in the pathway mediating the pupillary light reflex. In this work we found that electrical stimulation of the cerebellar nuclei (nucleus fastigius and nucleus interpositus bilaterally) evoked a discharge in the short ciliary nerves which innervate the intraocular muscles. The latency was 5.7 msec, which is short enough for a direct excitatory connexion from cerebellar efferents onto the preganglionic neurones in the Edinger-Westphal nucleus. These neurones are controlling the ciliary muscle of the lens system as well as the constrictor muscle of the pupil and it was therefore important to elucidate whether both of these groups participate in the discharge. Studies on interaction between the response to cerebellar stimulation and 'pupilloconstrictor' responses from optic tract fibres as well as recording from individual cells in the ciliary ganglion (identified with diffuse light stimuli) led to the conclusion that the short latency excitation is more or less confined to units controlling accommodation. Cerebellar inhibition (or disfacilitation) of longer latency affects both pupilloconstrictor and accommodation units.", "contents": "Cerebellar influence on parasympathetic neurones innervating intra-ocular muscles. Previous work has suggested that cerebellum may control the size of the pupil and transmission in the pathway mediating the pupillary light reflex. In this work we found that electrical stimulation of the cerebellar nuclei (nucleus fastigius and nucleus interpositus bilaterally) evoked a discharge in the short ciliary nerves which innervate the intraocular muscles. The latency was 5.7 msec, which is short enough for a direct excitatory connexion from cerebellar efferents onto the preganglionic neurones in the Edinger-Westphal nucleus. These neurones are controlling the ciliary muscle of the lens system as well as the constrictor muscle of the pupil and it was therefore important to elucidate whether both of these groups participate in the discharge. Studies on interaction between the response to cerebellar stimulation and 'pupilloconstrictor' responses from optic tract fibres as well as recording from individual cells in the ciliary ganglion (identified with diffuse light stimuli) led to the conclusion that the short latency excitation is more or less confined to units controlling accommodation. Cerebellar inhibition (or disfacilitation) of longer latency affects both pupilloconstrictor and accommodation units."}
{"id": "PMID:215269", "title": "Burst generation by electrically coupled network in the snail helisoma: analysis using computer simulation.", "content": "The effectiveness of electrical coupling between neurons as a mechanism for mediating single and repetitive bursts is investigated here using computer simulation. The cyberchron network in the snail Helisoma generates repetitive bursts controlling the animal's feeding behavior and served as the basic model for the simulation studies described in this paper. The action potential properties of individual neurons were modeled by the Rall equations describing generalized action potentials. Several properties of electrical coupling and its role in burst generation were demonstrated, including: (1) A neuron in an electrically coupled network can generate action potentials at a higher frequency than an isolated neuron with similar membrane properties due to the loading through the electrical junctions. However, the ability of electrically coupled neurons to generate high-frequency bursts of action potentials requires a concomitantly greater amount of driving current to overcome the junctional loading. (2) Temporal and spatial summation of synaptic input onto a neuron is maintained at its most effective level because the postsynaptic current is integrated across the long postsynaptic membrane time constant. (3) Initial simulations concentrated on a pair of electrically coupled neurons which were below threshold. Stimulation of one of the two neurons with a short pulse resulted in a reverberation or regenerative excitation between the two neurons. The reverberation terminated after a number of action potentials dependent on the specific model parameters. Similar results were obtained with a network containing a greater number (20) of model neurons if approximately one-half of the neurons were stimulated simultaneously. However, none of the cases studied produced more than a single discrete burst. (4) Simulations were also conducted on 20-neuron networks containing two subpopulations of model neurons differing in their values of coupling resistance and excitability. Some networks of this type required stimulation of only one cell to make the two subpopulations of model neurons reverberate with one another. Such simulations suggest the possibility that 'preferred' input pathways involving a small number of neurons would be capable of 'turning on' the activity of the entire network.", "contents": "Burst generation by electrically coupled network in the snail helisoma: analysis using computer simulation. The effectiveness of electrical coupling between neurons as a mechanism for mediating single and repetitive bursts is investigated here using computer simulation. The cyberchron network in the snail Helisoma generates repetitive bursts controlling the animal's feeding behavior and served as the basic model for the simulation studies described in this paper. The action potential properties of individual neurons were modeled by the Rall equations describing generalized action potentials. Several properties of electrical coupling and its role in burst generation were demonstrated, including: (1) A neuron in an electrically coupled network can generate action potentials at a higher frequency than an isolated neuron with similar membrane properties due to the loading through the electrical junctions. However, the ability of electrically coupled neurons to generate high-frequency bursts of action potentials requires a concomitantly greater amount of driving current to overcome the junctional loading. (2) Temporal and spatial summation of synaptic input onto a neuron is maintained at its most effective level because the postsynaptic current is integrated across the long postsynaptic membrane time constant. (3) Initial simulations concentrated on a pair of electrically coupled neurons which were below threshold. Stimulation of one of the two neurons with a short pulse resulted in a reverberation or regenerative excitation between the two neurons. The reverberation terminated after a number of action potentials dependent on the specific model parameters. Similar results were obtained with a network containing a greater number (20) of model neurons if approximately one-half of the neurons were stimulated simultaneously. However, none of the cases studied produced more than a single discrete burst. (4) Simulations were also conducted on 20-neuron networks containing two subpopulations of model neurons differing in their values of coupling resistance and excitability. Some networks of this type required stimulation of only one cell to make the two subpopulations of model neurons reverberate with one another. Such simulations suggest the possibility that 'preferred' input pathways involving a small number of neurons would be capable of 'turning on' the activity of the entire network."}
{"id": "PMID:215273", "title": "Pathways and polarities of synaptic interactions in the inner retina of the mudpuppy: I. Synaptic blocking studies.", "content": "Intracellular recording techniques were applied to the perfused retina-eyecup of the mudpuppy (Necturus maculosus). The use of input resistance measurements and the application of cobalt as a synaptic blocking agent provided evidence about the mode of synaptic operation for depolarizing and hyperpolarizing bipolar cell input to cells of the inner retina. In addition, cobalt produced a more rapid block of hyperpolarizing bipolars compared to depolarizing bipolars; in some postbipolar neurons, a temporary simplification of neuronal response waveform was observed and such cells resembled the depolarizing bipolar. These experiments suggest that bipolar cell input is excitatory and that response characteristics of third-order neurons is partially dependent on the relative input from the two types of bipolar cells.", "contents": "Pathways and polarities of synaptic interactions in the inner retina of the mudpuppy: I. Synaptic blocking studies. Intracellular recording techniques were applied to the perfused retina-eyecup of the mudpuppy (Necturus maculosus). The use of input resistance measurements and the application of cobalt as a synaptic blocking agent provided evidence about the mode of synaptic operation for depolarizing and hyperpolarizing bipolar cell input to cells of the inner retina. In addition, cobalt produced a more rapid block of hyperpolarizing bipolars compared to depolarizing bipolars; in some postbipolar neurons, a temporary simplification of neuronal response waveform was observed and such cells resembled the depolarizing bipolar. These experiments suggest that bipolar cell input is excitatory and that response characteristics of third-order neurons is partially dependent on the relative input from the two types of bipolar cells."}
{"id": "PMID:215274", "title": "Pathways and polarities of synaptic interactions in the inner retina of the mudpuppy: II. Insight revealed by an analysis of latency and threshold.", "content": "Intracellular recording experiments in the mudpuppy (Necturus maculosus) have demonstrated that depolarizing bipolars show a one-half to one log unit higher threshold to light stimuli and a longer latency when compared to hyperpolarizing bipolars. This threshold difference cannot be ascribed to differences in rod and cone connections. Experimentally it was possible to use these differences to evaluate postbipolar cell connections; such experiments support the idea that some neurons are connected to one or the other bipolar cell type, while on-off cells receive input from both.", "contents": "Pathways and polarities of synaptic interactions in the inner retina of the mudpuppy: II. Insight revealed by an analysis of latency and threshold. Intracellular recording experiments in the mudpuppy (Necturus maculosus) have demonstrated that depolarizing bipolars show a one-half to one log unit higher threshold to light stimuli and a longer latency when compared to hyperpolarizing bipolars. This threshold difference cannot be ascribed to differences in rod and cone connections. Experimentally it was possible to use these differences to evaluate postbipolar cell connections; such experiments support the idea that some neurons are connected to one or the other bipolar cell type, while on-off cells receive input from both."}
{"id": "PMID:215277", "title": "Excitability changes of dorsal inspiratory neurons during lung inflations as studied by measurement of antidromic invasion latencies.", "content": "(1) Glass microelectrodes were used to record extracellularly the activity of single dorsal (in the region of nucleus tractus solitarius (NTS)) inspiratory neurons in either chloralose- or pentobarbitone-anaesthetized, paralyzed cats. (2) In the lateral and ventral part of NTS, 89 cells were localized which responded antidromically to stimulation applied to the contralateral spinal cord (C3). Seventy were not excited by lung inflation and were classified as Ralpha, while 19 excited by that stimulus were classified as Rbeta. Usually Rbeta neurons fired both during each pump-induced lung inflation and during the central inspiratory excitation (CIE). (3) A technique similar to Merrill's recording small variations in the antidromic latency measured to the SD spike was used to ascertain excitability of Ralpha and Rbeta cells during the CIE time and during lung inflation in expiration. The technique was extended by averaging antidromic latency patterns within many respiratory cycles. (4) In the majority of Ralpha cells the averaging revealed a shortening of the antidromic latency during lung inflation in expiration, which indicated a subthreshold depolarization. Lengthening of the antidromic latency by this stimulus was never observed. These results are in disagreement with the concept of a direct inhibitory input from Rbeta to Ralpha neurons. (5) It is concluded that the dorsal Ralpha and Rbeta neurons differ less in their properties than was previously assumed on the basis of classical extracellular techniques. The inhibitory influence of pulmonary stretch receptor input on inspiratory discharge of Ralpha cells seems to be exerted through an indirect action on the source of the CIE.", "contents": "Excitability changes of dorsal inspiratory neurons during lung inflations as studied by measurement of antidromic invasion latencies. (1) Glass microelectrodes were used to record extracellularly the activity of single dorsal (in the region of nucleus tractus solitarius (NTS)) inspiratory neurons in either chloralose- or pentobarbitone-anaesthetized, paralyzed cats. (2) In the lateral and ventral part of NTS, 89 cells were localized which responded antidromically to stimulation applied to the contralateral spinal cord (C3). Seventy were not excited by lung inflation and were classified as Ralpha, while 19 excited by that stimulus were classified as Rbeta. Usually Rbeta neurons fired both during each pump-induced lung inflation and during the central inspiratory excitation (CIE). (3) A technique similar to Merrill's recording small variations in the antidromic latency measured to the SD spike was used to ascertain excitability of Ralpha and Rbeta cells during the CIE time and during lung inflation in expiration. The technique was extended by averaging antidromic latency patterns within many respiratory cycles. (4) In the majority of Ralpha cells the averaging revealed a shortening of the antidromic latency during lung inflation in expiration, which indicated a subthreshold depolarization. Lengthening of the antidromic latency by this stimulus was never observed. These results are in disagreement with the concept of a direct inhibitory input from Rbeta to Ralpha neurons. (5) It is concluded that the dorsal Ralpha and Rbeta neurons differ less in their properties than was previously assumed on the basis of classical extracellular techniques. The inhibitory influence of pulmonary stretch receptor input on inspiratory discharge of Ralpha cells seems to be exerted through an indirect action on the source of the CIE."}
{"id": "PMID:215278", "title": "Kinetic and pharmacologic characterization of gamma-aminobutyric acid receptive sites from mammalian brain.", "content": "Sodium-dependent (+Na) and sodium-independent (-Na) receptive sites for gamma-aminobutyric acid (GABA) have been characterized using synaptic plasma membranes from bovine and rat brain. Synaptic plasma membranes were prepared from either rat cerebellar cortex or calf cerebral cortex by discontinuous sucrose gradient flotation centrifugation of crude mitochondrial pellets, and assayed using equilibrium ligand binding assays to obtain the maximum binding capacity (Bmax) and the thermodynamic constant (KD). Values for KD from equilibrium studies were subsequently confirmed by kinetic analyses of association and dissociation reactions. The KD for +Na GABA binding (5.0 +/- 0.2 micron) corresponds to the apparent Michaelis constant for neuronal GABA transport (3.8 +/- 0.1 micron)22, while the KD for -Na binding (0.17 +/- 0.04 micron) agrees with that determined by Enna and Snyder for the putative postsynaptic receptor. Maximal binding activities of about 5 and 55 pmole/mg protein were obtained for -Na and +Na binding respectively. The pharmacologic specificities of the two sites were determined using competition binding studies. Nipecotic acid and diaminobutyric acid inhibit both synaptosomal GABA uptake (Ki approximately 25 micron and 120 micron respectively) and +Na binding of GABA to synaptic plasma membrane (IC50 approximately 40 micron and 350 micron respectively) but do not inhibit -Na binding. Bicuculline inhibits -Na [3H]GABA binding at low concentrations (IC50 approximately 15 micron), while affecting the uptake and +Na binding of [3H]GABA only at high concentrations (IC50 approximately 520 micron and 300 micron respectively). beta-Alanine inhibits the -Na binding site (IC50 approximately 100 micron), but is ineffective at the +Na binding site and does not interfere with synaptosomal uptake of GABA. Finally, chlorpromazine and N-ethylmaleimide inhibit the +Na binding, albeit at high concentrations (IC50 approximately 600 micron and 5 mM respectively) but are ineffective at the -Na binding site. From these results the -Na binding site is tentatively identified as a postsynaptic receptor and the +Na binding site is identified as the neuronal uptake receptive site.", "contents": "Kinetic and pharmacologic characterization of gamma-aminobutyric acid receptive sites from mammalian brain. Sodium-dependent (+Na) and sodium-independent (-Na) receptive sites for gamma-aminobutyric acid (GABA) have been characterized using synaptic plasma membranes from bovine and rat brain. Synaptic plasma membranes were prepared from either rat cerebellar cortex or calf cerebral cortex by discontinuous sucrose gradient flotation centrifugation of crude mitochondrial pellets, and assayed using equilibrium ligand binding assays to obtain the maximum binding capacity (Bmax) and the thermodynamic constant (KD). Values for KD from equilibrium studies were subsequently confirmed by kinetic analyses of association and dissociation reactions. The KD for +Na GABA binding (5.0 +/- 0.2 micron) corresponds to the apparent Michaelis constant for neuronal GABA transport (3.8 +/- 0.1 micron)22, while the KD for -Na binding (0.17 +/- 0.04 micron) agrees with that determined by Enna and Snyder for the putative postsynaptic receptor. Maximal binding activities of about 5 and 55 pmole/mg protein were obtained for -Na and +Na binding respectively. The pharmacologic specificities of the two sites were determined using competition binding studies. Nipecotic acid and diaminobutyric acid inhibit both synaptosomal GABA uptake (Ki approximately 25 micron and 120 micron respectively) and +Na binding of GABA to synaptic plasma membrane (IC50 approximately 40 micron and 350 micron respectively) but do not inhibit -Na binding. Bicuculline inhibits -Na [3H]GABA binding at low concentrations (IC50 approximately 15 micron), while affecting the uptake and +Na binding of [3H]GABA only at high concentrations (IC50 approximately 520 micron and 300 micron respectively). beta-Alanine inhibits the -Na binding site (IC50 approximately 100 micron), but is ineffective at the +Na binding site and does not interfere with synaptosomal uptake of GABA. Finally, chlorpromazine and N-ethylmaleimide inhibit the +Na binding, albeit at high concentrations (IC50 approximately 600 micron and 5 mM respectively) but are ineffective at the -Na binding site. From these results the -Na binding site is tentatively identified as a postsynaptic receptor and the +Na binding site is identified as the neuronal uptake receptive site."}
{"id": "PMID:215283", "title": "Interspecific variations in proteins synthesized by mammalian mitochondria.", "content": "The products of mitochondrial protein synthesis in established cell lines of various mammalian species were labelled with [35S]methionine and their number and apparent molecular weights determined by sodium dodecyl sulfate polyacrylamide slab gel electrophoresis and fluorography. Proteins synthesized by isolated rat liver mitochondria were labelled with [3H]valine and similarly characterized. Each species had a distinctive pattern of from 10 to 13 mitochondrially synthesized proteins with apparent molecular weights between 10,000 and 50,000. No differences were detected in the number or electrophoretic mobility of the mitochondrially synthesized proteins of SV-40-transformed and nontransformed WI-38 cells.", "contents": "Interspecific variations in proteins synthesized by mammalian mitochondria. The products of mitochondrial protein synthesis in established cell lines of various mammalian species were labelled with [35S]methionine and their number and apparent molecular weights determined by sodium dodecyl sulfate polyacrylamide slab gel electrophoresis and fluorography. Proteins synthesized by isolated rat liver mitochondria were labelled with [3H]valine and similarly characterized. Each species had a distinctive pattern of from 10 to 13 mitochondrially synthesized proteins with apparent molecular weights between 10,000 and 50,000. No differences were detected in the number or electrophoretic mobility of the mitochondrially synthesized proteins of SV-40-transformed and nontransformed WI-38 cells."}
{"id": "PMID:215284", "title": "Selective degradation with phospholipases D and C of radioactive isomeric spin-labelled lipids bound to guinea pig liver microsomal membranes.", "content": "Membrane-bound lipids of isolated guinea pig liver microsomal membranes were selectively enzymatically labelled with isomeric (5-, 12-, and 16-)doxyl stearic acid. After reisolation, the membranes were degraded with phospholipases D and C under conditions not requiring detergents or organic solvent activators. The degradation of membrane-bound lipids occurred according to the recognized specificity of phospholipases D and C. Temperature-induced changes of degraded membranes containing radioactive spin-labelled isomeric lipids were followed by the electron spin resonance and spectral changes correlated with the lipid composition of membranes. Discontinuities in plots of experimental spectral parameters versus temperature detected in the case of microsomal membranes before and after degradation with phospholipases D and C were attributed to lipid-protein and lipid-lipid interaction(s). On the basis of these and control experiments, discontinuity at around 10-12 degrees C was attributed to the microsomal membrane phosphatidylcholine intrinsic microsomal membrane protein interaction(s), while discontinuities detected at 19-21 degrees C approximately and at 20-30 degrees C approximately were attributed to the phase separation of Ca or Zn salts of membranous phosphatidic acid and to the similar phenomenon involving membrane-bound diglycerides respectively.", "contents": "Selective degradation with phospholipases D and C of radioactive isomeric spin-labelled lipids bound to guinea pig liver microsomal membranes. Membrane-bound lipids of isolated guinea pig liver microsomal membranes were selectively enzymatically labelled with isomeric (5-, 12-, and 16-)doxyl stearic acid. After reisolation, the membranes were degraded with phospholipases D and C under conditions not requiring detergents or organic solvent activators. The degradation of membrane-bound lipids occurred according to the recognized specificity of phospholipases D and C. Temperature-induced changes of degraded membranes containing radioactive spin-labelled isomeric lipids were followed by the electron spin resonance and spectral changes correlated with the lipid composition of membranes. Discontinuities in plots of experimental spectral parameters versus temperature detected in the case of microsomal membranes before and after degradation with phospholipases D and C were attributed to lipid-protein and lipid-lipid interaction(s). On the basis of these and control experiments, discontinuity at around 10-12 degrees C was attributed to the microsomal membrane phosphatidylcholine intrinsic microsomal membrane protein interaction(s), while discontinuities detected at 19-21 degrees C approximately and at 20-30 degrees C approximately were attributed to the phase separation of Ca or Zn salts of membranous phosphatidic acid and to the similar phenomenon involving membrane-bound diglycerides respectively."}
{"id": "PMID:215285", "title": "Low density lipoprotein turnover in swine.", "content": "The catabolism of intravenously injected 125I-labelled low density lipoproteins (LDL) was followed in normal miniature swine for 2 weeks. When compared with the two-exponential model, the decay curve of the plasma radioactivity associated with the LDL fraction was best described by a three-exponential model. In this system, the half-lives were 4.5 +/- 3.7, 19.7 +/- 6.6, and 127 +/- 70 h (mean of four studies). Assuming a kinetic model with metabolism of LDL in the rapidly equilibrating compartment and two slower equilibrating compartments (a model requiring three exponentials), the mean fractional catabolic rate for apo-LDL was calculated to be 0.015 h-1. Therefore, if at steady state, the synthetic rate for apo-LDL in the same pigs would be 5.6 +/- 4.1 mg/h. Different kinetic models using two or three exponentials would provide different values for the synthetic rate of apo-LDL. However, in view of the known existence of at least three major equilibrating pools for LDL in plasma, liver, and lymph, and in view of the present results, the kinetic model for LDL metabolism should be better represented by a three-exponential system.", "contents": "Low density lipoprotein turnover in swine. The catabolism of intravenously injected 125I-labelled low density lipoproteins (LDL) was followed in normal miniature swine for 2 weeks. When compared with the two-exponential model, the decay curve of the plasma radioactivity associated with the LDL fraction was best described by a three-exponential model. In this system, the half-lives were 4.5 +/- 3.7, 19.7 +/- 6.6, and 127 +/- 70 h (mean of four studies). Assuming a kinetic model with metabolism of LDL in the rapidly equilibrating compartment and two slower equilibrating compartments (a model requiring three exponentials), the mean fractional catabolic rate for apo-LDL was calculated to be 0.015 h-1. Therefore, if at steady state, the synthetic rate for apo-LDL in the same pigs would be 5.6 +/- 4.1 mg/h. Different kinetic models using two or three exponentials would provide different values for the synthetic rate of apo-LDL. However, in view of the known existence of at least three major equilibrating pools for LDL in plasma, liver, and lymph, and in view of the present results, the kinetic model for LDL metabolism should be better represented by a three-exponential system."}
{"id": "PMID:215286", "title": "Oxytocin binding sites in lactating rabbit mammary gland.", "content": "Material which specifically binds oxytocin was prepared from a crude preparation of lactating rabbit mammary gland by purification on a sucrose density gradient. On examination of activities of enzyme markers and the molar ratio of cholesterol to phospholipid, this material was considered to be a highly purified plasma membrane fraction. For the determination of specificity and time course of oxytocin binding, a Scatchard plot analysis was carried out for the crude and purified fractions. Dissociation constant (Kd) and binding capacity values were found to be as follows: crude, Kd equals 1.83 X 10(-9) M, capacity equals 670 fmol/mg protein; purified, Kd equals 2.8 X 10(-9) M, capacity equals 1700 fmol/mg protein. Treatment of the purified material with different detergents resulted in loss of all [3H]oxytocin binding capacity. However, preincubation of this material with [3H]oxytocin prior to detergent treatment resulted in solubilization of a receptor-hormone complex. This complex remained in the supernatant even after centrifugation at 210 000 X g for 30 min. Using oxytocin analogs, we have shown this solubilized complex to be oxytocin specific.", "contents": "Oxytocin binding sites in lactating rabbit mammary gland. Material which specifically binds oxytocin was prepared from a crude preparation of lactating rabbit mammary gland by purification on a sucrose density gradient. On examination of activities of enzyme markers and the molar ratio of cholesterol to phospholipid, this material was considered to be a highly purified plasma membrane fraction. For the determination of specificity and time course of oxytocin binding, a Scatchard plot analysis was carried out for the crude and purified fractions. Dissociation constant (Kd) and binding capacity values were found to be as follows: crude, Kd equals 1.83 X 10(-9) M, capacity equals 670 fmol/mg protein; purified, Kd equals 2.8 X 10(-9) M, capacity equals 1700 fmol/mg protein. Treatment of the purified material with different detergents resulted in loss of all [3H]oxytocin binding capacity. However, preincubation of this material with [3H]oxytocin prior to detergent treatment resulted in solubilization of a receptor-hormone complex. This complex remained in the supernatant even after centrifugation at 210 000 X g for 30 min. Using oxytocin analogs, we have shown this solubilized complex to be oxytocin specific."}
{"id": "PMID:215287", "title": "Heterogeneity of human plasma low density lipoprotein.", "content": "Low density lipoprotein (LDL) was fractionated into subspecies by the use of DEAE-agarose column chromatography and the peptide compositions of the LDL subspecies which eluted at different NaCl concentrations were determined. LDL which elutes at low NaCl concentration has relatively less non-B apoprotein than does LDL which elutes at high salt concentration. The LDL subspecies which elute at high NaCl concentration contain more apo A-1 than do those which elute at the lower NaCl molarity. These results indicate that LDL consists of subfractions which differ in their peptide compositions.", "contents": "Heterogeneity of human plasma low density lipoprotein. Low density lipoprotein (LDL) was fractionated into subspecies by the use of DEAE-agarose column chromatography and the peptide compositions of the LDL subspecies which eluted at different NaCl concentrations were determined. LDL which elutes at low NaCl concentration has relatively less non-B apoprotein than does LDL which elutes at high salt concentration. The LDL subspecies which elute at high NaCl concentration contain more apo A-1 than do those which elute at the lower NaCl molarity. These results indicate that LDL consists of subfractions which differ in their peptide compositions."}
{"id": "PMID:215288", "title": "Determination of the rates of synthesis and degradation of adenosine 3',5'-cyclic monophosphate in Escherichia coli CRP- and CRP+ strains.", "content": "We have developed a method for estimating the rates of synthesis and degradation of adenosine 3',5'-cyclic monophosphate (cAMP) in Escherichia coli during balanced growth. Applying this method, we have found that an E. coli CRP- mutant 5333 (deficient for cAMP receptor protein) synthesizes cAMP about 25 times faster than does its CRP+ parent 1100. This accounts for the abnormally high intracellular and extracellular cAMP accumulation in 5333.", "contents": "Determination of the rates of synthesis and degradation of adenosine 3',5'-cyclic monophosphate in Escherichia coli CRP- and CRP+ strains. We have developed a method for estimating the rates of synthesis and degradation of adenosine 3',5'-cyclic monophosphate (cAMP) in Escherichia coli during balanced growth. Applying this method, we have found that an E. coli CRP- mutant 5333 (deficient for cAMP receptor protein) synthesizes cAMP about 25 times faster than does its CRP+ parent 1100. This accounts for the abnormally high intracellular and extracellular cAMP accumulation in 5333."}
{"id": "PMID:215290", "title": "Metabolic responses of Sertoli cells in culture to various concentrations of follicle stimulating hormone and cholera toxin.", "content": "The concentration of cholera toxin required for half-maximal stimulation of cAMP production by Sertoli cell enriched cultures (4.48 X 10(2) microgram/ml) is greater than that required for half-maximal stimulation of 17beta-estradiol synthesis from testosterone (2.34 X 10(-4) microgram/ml), [3H]thymidine incorporation into DNA (1.48 X 10(-5) microgram/ml), or androgen binding protein production (2.43 X 10(-6) microgram/ml). The same relative dose response hierarchy was obtained with respect to stimulation of Sertoli cells with follicle stimulating hormone (FSH) preparations. Again, highest concentrations were required to elicit maximal cAMP production. The data are discussed in relation to an apparent paradox: If cAMP is the mediating 'second messenger' following stimulation by FSH or cholera toxin, why should highest concentrations of these agents be required to elicit 50% of maximal cAMP levels?", "contents": "Metabolic responses of Sertoli cells in culture to various concentrations of follicle stimulating hormone and cholera toxin. The concentration of cholera toxin required for half-maximal stimulation of cAMP production by Sertoli cell enriched cultures (4.48 X 10(2) microgram/ml) is greater than that required for half-maximal stimulation of 17beta-estradiol synthesis from testosterone (2.34 X 10(-4) microgram/ml), [3H]thymidine incorporation into DNA (1.48 X 10(-5) microgram/ml), or androgen binding protein production (2.43 X 10(-6) microgram/ml). The same relative dose response hierarchy was obtained with respect to stimulation of Sertoli cells with follicle stimulating hormone (FSH) preparations. Again, highest concentrations were required to elicit maximal cAMP production. The data are discussed in relation to an apparent paradox: If cAMP is the mediating 'second messenger' following stimulation by FSH or cholera toxin, why should highest concentrations of these agents be required to elicit 50% of maximal cAMP levels?"}
{"id": "PMID:215291", "title": "Sphingomyelinases in human tissues. IV. Purification of sphingomyelinase from human placenta and effect of Triton X-100.", "content": "Sphingomyelinase was purified about 1700-fold from human placenta. The major steps in the procedure included chromatography on Concanavalin A-Sepharose, Sepharose 6B, and carboxymethyl-Sepharose (CM-Sepharose). The final preparation was stable for at least 3 months when stored at 4 degrees C. The enzyme was found to be heterogeneous on CM-Sepharose and isoelectric focusing. Triton X-100 which was present in most buffers used during the purification appears to be partially responsible for the heterogeneity. When Triton X-100 is removed by treatment with Bio Beads, heterogeneity was reduced. However, removal of the detergent also leads to loss of enzyme activity which could not be restored by readdition of Triton X-100. The data suggest that sphingomyelinase has a high hydrophobic character and that both its stability and electrofocusing behaviour are influenced by interaction with the nonionic detergent.", "contents": "Sphingomyelinases in human tissues. IV. Purification of sphingomyelinase from human placenta and effect of Triton X-100. Sphingomyelinase was purified about 1700-fold from human placenta. The major steps in the procedure included chromatography on Concanavalin A-Sepharose, Sepharose 6B, and carboxymethyl-Sepharose (CM-Sepharose). The final preparation was stable for at least 3 months when stored at 4 degrees C. The enzyme was found to be heterogeneous on CM-Sepharose and isoelectric focusing. Triton X-100 which was present in most buffers used during the purification appears to be partially responsible for the heterogeneity. When Triton X-100 is removed by treatment with Bio Beads, heterogeneity was reduced. However, removal of the detergent also leads to loss of enzyme activity which could not be restored by readdition of Triton X-100. The data suggest that sphingomyelinase has a high hydrophobic character and that both its stability and electrofocusing behaviour are influenced by interaction with the nonionic detergent."}
{"id": "PMID:215292", "title": "Spin-label study of the relation between enzymatic activity and lipid-protein organization in reconstituted cytochrome c oxidase.", "content": "Lipid-depleted cytochrome c oxidase (EC 1.9.3.1) containing less than 20 microgram lipids per milligram protein was reconstituted with pure phospholipids of well-defined chemical structure and fatty acid composition without using detergents and (or) sonication. For the maximal restoration of electron transport activity, lipid-depleted cytochrome c oxidase required acidic phospholipds such as phosphatidylglycerol or phosphatidylserine or lysophospholipids such as lysophosphatidylcholine or lysophosphatidic acid, but no specific phospholipid fatty acid composition was necessary. The organization of the lipid environment of the reconstituted cytochrome c oxidase, having a well-defined lipid composition, morphology, and a high specific activity, was examined by electron spin resonance spectroscopy using 2-(14-carboxytetradecyl)-2-ethyl-4,4-dimethyl-3-oxazolidinyloxyl (16-doxyl stearic acid) and 16-doxyl stearic acid - containing phosphatidylglycerol. The presence of boundary lipid was established in both lamellar and micellar organizations of reconstituted cytochrome c oxidase and was not necessarily related to the enzymatic activity of the complex. Our results have established that aside from structural considerations, the boundary lipid, at least in the reconstituted cytochrome c oxidase, is a necessary but not sufficient condition for the enzymatic expression of cytochrome c oxidase.", "contents": "Spin-label study of the relation between enzymatic activity and lipid-protein organization in reconstituted cytochrome c oxidase. Lipid-depleted cytochrome c oxidase (EC 1.9.3.1) containing less than 20 microgram lipids per milligram protein was reconstituted with pure phospholipids of well-defined chemical structure and fatty acid composition without using detergents and (or) sonication. For the maximal restoration of electron transport activity, lipid-depleted cytochrome c oxidase required acidic phospholipds such as phosphatidylglycerol or phosphatidylserine or lysophospholipids such as lysophosphatidylcholine or lysophosphatidic acid, but no specific phospholipid fatty acid composition was necessary. The organization of the lipid environment of the reconstituted cytochrome c oxidase, having a well-defined lipid composition, morphology, and a high specific activity, was examined by electron spin resonance spectroscopy using 2-(14-carboxytetradecyl)-2-ethyl-4,4-dimethyl-3-oxazolidinyloxyl (16-doxyl stearic acid) and 16-doxyl stearic acid - containing phosphatidylglycerol. The presence of boundary lipid was established in both lamellar and micellar organizations of reconstituted cytochrome c oxidase and was not necessarily related to the enzymatic activity of the complex. Our results have established that aside from structural considerations, the boundary lipid, at least in the reconstituted cytochrome c oxidase, is a necessary but not sufficient condition for the enzymatic expression of cytochrome c oxidase."}
{"id": "PMID:215293", "title": "N-Terminal amino acid sequence of rat tonin: homology with serine proteases.", "content": "In this paper, we present the amino-terminal sequence of rat tonin, an endopeptidase responsible for the conversion of angiotensinogen, the tetradecapeptide renin substrate, or angiotensin I to angiotensin II. It is shown that isoleucine and proline occupy the amino- and carboxy-terminal residues respectively. The N-terminal sequence analysis permitted the identification of 34 out of the first 40 residues of the single polypeptide chain composed of 272 amino acids. These results showed an extensive homology with the sequence of many serine proteases of the trypsin-chymotrypsin family. This information, coupled with the slow inhibition of tonin by diisopropylfluorophosphate, classified this enzyme as a selective endopeptidase of the active serine protease family.", "contents": "N-Terminal amino acid sequence of rat tonin: homology with serine proteases. In this paper, we present the amino-terminal sequence of rat tonin, an endopeptidase responsible for the conversion of angiotensinogen, the tetradecapeptide renin substrate, or angiotensin I to angiotensin II. It is shown that isoleucine and proline occupy the amino- and carboxy-terminal residues respectively. The N-terminal sequence analysis permitted the identification of 34 out of the first 40 residues of the single polypeptide chain composed of 272 amino acids. These results showed an extensive homology with the sequence of many serine proteases of the trypsin-chymotrypsin family. This information, coupled with the slow inhibition of tonin by diisopropylfluorophosphate, classified this enzyme as a selective endopeptidase of the active serine protease family."}
{"id": "PMID:215294", "title": "Relationship of herpes simplex virus type-2 antibodies and squamous dysplasia to cervical carcinoma in situ.", "content": "Serum specimens from 75 women with cervical carcinoma in situ, 84 with squamous dysplasia, and 132 controls, who had previously been interviewed and tested for complement fixing antibodies against a number of organisms, were analyzed for HSV-2 antibodies. Carcinoma in situ and severe dysplasia were associated with HSV-2 antibodies. Mild dysplasia was related to evidence of prior infection by Trichomonas vaginalis, adenoviruses, and Mycoplasma pneumoniae, plus a history of vaginal discharge. Severe dysplasia was less strongly related to these variables. The relative risk of dysplasia increased with the number of different pathogens by which a woman had been infected. It is concluded that HSV-2 may be a cause of carcinoma in situ; that much dysplasia is a nonspecific reaction of the cervical epithelium to chronic inflammation; and that dysplastic lesions that are caused by HSV-2, and hence may be a precursor to carcinoma in situ, tend to be distinguished by their severity.", "contents": "Relationship of herpes simplex virus type-2 antibodies and squamous dysplasia to cervical carcinoma in situ. Serum specimens from 75 women with cervical carcinoma in situ, 84 with squamous dysplasia, and 132 controls, who had previously been interviewed and tested for complement fixing antibodies against a number of organisms, were analyzed for HSV-2 antibodies. Carcinoma in situ and severe dysplasia were associated with HSV-2 antibodies. Mild dysplasia was related to evidence of prior infection by Trichomonas vaginalis, adenoviruses, and Mycoplasma pneumoniae, plus a history of vaginal discharge. Severe dysplasia was less strongly related to these variables. The relative risk of dysplasia increased with the number of different pathogens by which a woman had been infected. It is concluded that HSV-2 may be a cause of carcinoma in situ; that much dysplasia is a nonspecific reaction of the cervical epithelium to chronic inflammation; and that dysplastic lesions that are caused by HSV-2, and hence may be a precursor to carcinoma in situ, tend to be distinguished by their severity."}
{"id": "PMID:215295", "title": "Silica reaction simulating fibrous histiocytoma.", "content": "An unusual foreign body reaction to silica (quartz), resembling fibrous histiocytoma, is described in 7 patients (age range 22 to 71 years). These lesions occurred in the inguinal region (4 cases) or the abdominal wall (3 cases), and in 5 instances were associated with a history of injection at the same site 10 to 41 years previously. Most commonly the injection consisted of the administration of a sclerosing agent for the repair of a hernia. Microscopically these lesions contained broad sheets of histiocytes separated by bands or concentrically lamellated nodules of collagen. Intra- and extra-cellular birefringent crystals, identified by x-ray diffraction as silica (quartz), were present in all cases and served to distinguish this process from a true neoplasm. Although the injection therapy for hernia is now obsolete, it was formerly practiced in the United States with a variety of sclerosing agents including silica (quartz). Since these lesions are often confused with a benign or malignant fibrous histiocytoma it is recommended that fibro-histiocytic lesions associated with a previous hernia or injection at the same site be examined for the presence of silica.", "contents": "Silica reaction simulating fibrous histiocytoma. An unusual foreign body reaction to silica (quartz), resembling fibrous histiocytoma, is described in 7 patients (age range 22 to 71 years). These lesions occurred in the inguinal region (4 cases) or the abdominal wall (3 cases), and in 5 instances were associated with a history of injection at the same site 10 to 41 years previously. Most commonly the injection consisted of the administration of a sclerosing agent for the repair of a hernia. Microscopically these lesions contained broad sheets of histiocytes separated by bands or concentrically lamellated nodules of collagen. Intra- and extra-cellular birefringent crystals, identified by x-ray diffraction as silica (quartz), were present in all cases and served to distinguish this process from a true neoplasm. Although the injection therapy for hernia is now obsolete, it was formerly practiced in the United States with a variety of sclerosing agents including silica (quartz). Since these lesions are often confused with a benign or malignant fibrous histiocytoma it is recommended that fibro-histiocytic lesions associated with a previous hernia or injection at the same site be examined for the presence of silica."}
{"id": "PMID:215296", "title": "Bronchiolo-alveolar carcinoma: a correlative clinical and cytologic study.", "content": "From 1970 to 1977, 101 patients with bronchiolo-alveolar carcinoma were admitted to the Toronto General Hospital. Cytology preparations from 97 patients were reviewed and analyzed in correlation with biologic behavior of the tumours. The value of cytologic diagnosis was reassessed. It appears that routine cytology methods were of limited value in the investigation of patients with a peripheral solitary tumor and therefore, percutaneous fine needle aspiration with positive results in 92% of cases examined, was the only useful cytologic examination for this type of lesion. For multicentric tumors, routine cytology methods achieved positive results in 87.9% of cases and fine needle aspiration 100%. Based on cytomorphologic features, bronchioloalveolar carcinoma can be subclassified into three types: secretory, nonsecretory and poorly differentiated. In this series, 84% of solitary tumors were secretory or nonsecretory type with favorable prognosis, and 16% of solitary tumors were poorly differentiated type with poor prognosis. 55.2% of multicentric tumors were poorly differentiated type and 77.3% of multicentric tumors showed positive lymph nodes at surgery. Our results demonstrate that patients with multicentric or poorly differentiated tumors had poor prognosis.", "contents": "Bronchiolo-alveolar carcinoma: a correlative clinical and cytologic study. From 1970 to 1977, 101 patients with bronchiolo-alveolar carcinoma were admitted to the Toronto General Hospital. Cytology preparations from 97 patients were reviewed and analyzed in correlation with biologic behavior of the tumours. The value of cytologic diagnosis was reassessed. It appears that routine cytology methods were of limited value in the investigation of patients with a peripheral solitary tumor and therefore, percutaneous fine needle aspiration with positive results in 92% of cases examined, was the only useful cytologic examination for this type of lesion. For multicentric tumors, routine cytology methods achieved positive results in 87.9% of cases and fine needle aspiration 100%. Based on cytomorphologic features, bronchioloalveolar carcinoma can be subclassified into three types: secretory, nonsecretory and poorly differentiated. In this series, 84% of solitary tumors were secretory or nonsecretory type with favorable prognosis, and 16% of solitary tumors were poorly differentiated type with poor prognosis. 55.2% of multicentric tumors were poorly differentiated type and 77.3% of multicentric tumors showed positive lymph nodes at surgery. Our results demonstrate that patients with multicentric or poorly differentiated tumors had poor prognosis."}
{"id": "PMID:215297", "title": "Mixed mesodermal tumor and clear cell carcinoma arising in ovarian endometriosis.", "content": "A case is reported of clear cell carcinoma, arising as several papillary masses from the lining of an endometrial cyst within the ovary, associated with a mixed mesodermal tumor arising in the stalk of the largest papillary nodule. The origin of this tumor from within a focus of endometriosis lends support to the theory that both the epithelial and mesodermal components are of M\u00fcllerian (Paramesonephric) origin.", "contents": "Mixed mesodermal tumor and clear cell carcinoma arising in ovarian endometriosis. A case is reported of clear cell carcinoma, arising as several papillary masses from the lining of an endometrial cyst within the ovary, associated with a mixed mesodermal tumor arising in the stalk of the largest papillary nodule. The origin of this tumor from within a focus of endometriosis lends support to the theory that both the epithelial and mesodermal components are of M\u00fcllerian (Paramesonephric) origin."}
{"id": "PMID:215298", "title": "Spinal subarachnoid metastasis from primary intracranial glioblastoma multiforme.", "content": "Twenty-five patients with glioblastoma multiforme were autopsied at our institution in 7 years. Spinal cords were examined in 20 and 5 were found to have spinal leptomeningeal metastases. Clinical and neuropathological findings of these 5 patients are presented and factors possibility influencing such spread are analyzed. Review of previous studies of intracranial glioblastomas discloses only 14 reported cases with spinal leptomeningeal metastases confirmed at autopsy since 1931. We conclude that spinal leptomeningeal metastases in glioblastoma multiforme are a common occurrence. These findings are of little significance at present with our poor success at control of the primary lesion. Frequency of involvement of the spinal subarachnoid space will be significant, when we are able to better treat the primary tumor. Knowledge of the significant possibility of this phenomenon will allow earlier and more frequent clinical diagnosis.", "contents": "Spinal subarachnoid metastasis from primary intracranial glioblastoma multiforme. Twenty-five patients with glioblastoma multiforme were autopsied at our institution in 7 years. Spinal cords were examined in 20 and 5 were found to have spinal leptomeningeal metastases. Clinical and neuropathological findings of these 5 patients are presented and factors possibility influencing such spread are analyzed. Review of previous studies of intracranial glioblastomas discloses only 14 reported cases with spinal leptomeningeal metastases confirmed at autopsy since 1931. We conclude that spinal leptomeningeal metastases in glioblastoma multiforme are a common occurrence. These findings are of little significance at present with our poor success at control of the primary lesion. Frequency of involvement of the spinal subarachnoid space will be significant, when we are able to better treat the primary tumor. Knowledge of the significant possibility of this phenomenon will allow earlier and more frequent clinical diagnosis."}
{"id": "PMID:215299", "title": "Growth rates of small cell bronchogenic carcinomas.", "content": "In reviewing a series of 144 patients with small cell bronchogenic carcinoma, 12 were found to have serially measurable roentgenographic lesions prior to therapy. Although caliper-based measurements and a silhouette cutout method gave comparable sets of tumor doubling time data, inter-observer variability was less with the silhouette cutout method. Tumor doubling times in small cell bronchogenic carcinoma ranged between 25 and 160 days, with a median of 77 days, a log mean of 81 days, and an arithmetic mean of 91 days. There was no apparent relation between tumor doubling time and tumor location, histologic subtype, response to therapy, or patient survival. The data indicate that small cell bronchogenic carcinoma of the lung is a relatively slowly growing tumor. Assuming that late subclinical disease exhibits growth characteristics that are similar to those seen in the clinical stages of growth, it can be estimated that residual body tumor burdens of 1 X 10(6) cells may be followed by tumor recurrence times of 2 years or longer; the likelihood of \"cure\" should not be entertained in patients with disease-free intervals shorter than 4-5 years.", "contents": "Growth rates of small cell bronchogenic carcinomas. In reviewing a series of 144 patients with small cell bronchogenic carcinoma, 12 were found to have serially measurable roentgenographic lesions prior to therapy. Although caliper-based measurements and a silhouette cutout method gave comparable sets of tumor doubling time data, inter-observer variability was less with the silhouette cutout method. Tumor doubling times in small cell bronchogenic carcinoma ranged between 25 and 160 days, with a median of 77 days, a log mean of 81 days, and an arithmetic mean of 91 days. There was no apparent relation between tumor doubling time and tumor location, histologic subtype, response to therapy, or patient survival. The data indicate that small cell bronchogenic carcinoma of the lung is a relatively slowly growing tumor. Assuming that late subclinical disease exhibits growth characteristics that are similar to those seen in the clinical stages of growth, it can be estimated that residual body tumor burdens of 1 X 10(6) cells may be followed by tumor recurrence times of 2 years or longer; the likelihood of \"cure\" should not be entertained in patients with disease-free intervals shorter than 4-5 years."}
{"id": "PMID:215300", "title": "Lung cancer as a second primary.", "content": "An unusually high association of other primary cancers (9.7%) was found during the analysis of 403 consecutive cases of carcinoma of the lung diagnosed at DGMC between 1960 and 1975. Incidence by stage included 17.3% for Stage I (75 cases) and 16.9% for Stage II (59 cases). Median survival by stage was not adversely affected by the associated malignancy. Incidence by histologic type was 15.6% for adenocarcinoma (132 cases), 7.7% for epidermoid (130 cases), 1.5% for oat (small cell) (67 cases), 12.5% for large cell (40 cases) and 11.8% for undifferentiated anaplastic type (34 cases). Of 31 cases of Stage I adenocarcinoma, 9 (29%) had second malignancies. Both adenocarcinoma and epidermoid carcinoma exhibited decreasing association of second malignances with increasing stage of lung cancer. The head and neck region was the location of the nonlung malignancy in 22 cases and the GU system in 11 cases. Two cases each of colon carcinoma and basal cell skin carcinoma were found and there was one case each of carcinoma of the pancreas, lymphoma and melanoma. The diagnosis of lung cancer was made first in only 3 instances. The appearance of solitary nodules in patients with known malignancy should receive strong consideration for vigorous diagnostic and therapeutic procedures. Future studies should consider carcinogenic stimuli that may be common etiologic factors in both malignancies.", "contents": "Lung cancer as a second primary. An unusually high association of other primary cancers (9.7%) was found during the analysis of 403 consecutive cases of carcinoma of the lung diagnosed at DGMC between 1960 and 1975. Incidence by stage included 17.3% for Stage I (75 cases) and 16.9% for Stage II (59 cases). Median survival by stage was not adversely affected by the associated malignancy. Incidence by histologic type was 15.6% for adenocarcinoma (132 cases), 7.7% for epidermoid (130 cases), 1.5% for oat (small cell) (67 cases), 12.5% for large cell (40 cases) and 11.8% for undifferentiated anaplastic type (34 cases). Of 31 cases of Stage I adenocarcinoma, 9 (29%) had second malignancies. Both adenocarcinoma and epidermoid carcinoma exhibited decreasing association of second malignances with increasing stage of lung cancer. The head and neck region was the location of the nonlung malignancy in 22 cases and the GU system in 11 cases. Two cases each of colon carcinoma and basal cell skin carcinoma were found and there was one case each of carcinoma of the pancreas, lymphoma and melanoma. The diagnosis of lung cancer was made first in only 3 instances. The appearance of solitary nodules in patients with known malignancy should receive strong consideration for vigorous diagnostic and therapeutic procedures. Future studies should consider carcinogenic stimuli that may be common etiologic factors in both malignancies."}
{"id": "PMID:215301", "title": "Coexistence of bilateral pheochromocytoma and pancreatic islet cell tumor: report of a case and review of the literature.", "content": "A 14-year-old Japanese male with a previously undescribed combination of bilateral pheochromocytoma and an islet cell tumor of the pancreas is presented. The combination of endocrine neoplasms in this patient overlaps multiple endocrine neoplasia (MEN) Type 1 and Type 2. A total of 14 reported cases of MEN overlapping Type 1 and Type 2 is reviewed. Of the 14, 7 patients with acromegaly developed a paraganglioma(s), 2 patients with Sipple syndrome had a pituitary adenoma, and in the other 5 patients, an intestinal carcinoid or a pancreatic islet-cell tumor occurred in association with either a thyroid medullary carcinoma or a paraganglioma(s). We believe that the occurrence of MEN overlapping Type 1 and Type 2 is more than a fortuitous association, and can be explained on the basis of the neuroectodermal origin.", "contents": "Coexistence of bilateral pheochromocytoma and pancreatic islet cell tumor: report of a case and review of the literature. A 14-year-old Japanese male with a previously undescribed combination of bilateral pheochromocytoma and an islet cell tumor of the pancreas is presented. The combination of endocrine neoplasms in this patient overlaps multiple endocrine neoplasia (MEN) Type 1 and Type 2. A total of 14 reported cases of MEN overlapping Type 1 and Type 2 is reviewed. Of the 14, 7 patients with acromegaly developed a paraganglioma(s), 2 patients with Sipple syndrome had a pituitary adenoma, and in the other 5 patients, an intestinal carcinoid or a pancreatic islet-cell tumor occurred in association with either a thyroid medullary carcinoma or a paraganglioma(s). We believe that the occurrence of MEN overlapping Type 1 and Type 2 is more than a fortuitous association, and can be explained on the basis of the neuroectodermal origin."}
{"id": "PMID:215302", "title": "Damage of proliferating lymphoid cell deoxyribonucleic acid by methyl methanesulfonate and N-acetoxy-2-acetylaminofluorene.", "content": "Replicative synthesis of deoxyribonucleic acid by splenic lymphoid cells cultured from C57BL/6J strain mice and stimulated to proliferate with concanavalin A (Con A) was strongly suppressed by short exposure (10-60 min) of the cells to the direct-acting carcinogens methyl methanesulfonate or N-acetoxy-2-acetylaminofluorene. Carcinogen-treated lymphoid cells failed to recover stimulated levels of replicative synthesis after incubation for several hours in fresh medium without carcinogen. In contrast, spleen cells treated with hydroxyurea (a metabolic inhibitor of deoxyribonucleic acid replication) fully recovered stimulated rates of replicative synthesis upon incubation in medium without hydroxyurea. Furthermore, the inhibition of replicative synthesis by the carcinogens was accompanied by marked stimulation of deoxyribonucleic acid repair synthesis. Concomitant measurement of replicative and repair synthesis appears to be an effective approach for the in vitro study of carcinogen-induced damage in the deoxyribonucleic acid of proliferating lymphoid cells.", "contents": "Damage of proliferating lymphoid cell deoxyribonucleic acid by methyl methanesulfonate and N-acetoxy-2-acetylaminofluorene. Replicative synthesis of deoxyribonucleic acid by splenic lymphoid cells cultured from C57BL/6J strain mice and stimulated to proliferate with concanavalin A (Con A) was strongly suppressed by short exposure (10-60 min) of the cells to the direct-acting carcinogens methyl methanesulfonate or N-acetoxy-2-acetylaminofluorene. Carcinogen-treated lymphoid cells failed to recover stimulated levels of replicative synthesis after incubation for several hours in fresh medium without carcinogen. In contrast, spleen cells treated with hydroxyurea (a metabolic inhibitor of deoxyribonucleic acid replication) fully recovered stimulated rates of replicative synthesis upon incubation in medium without hydroxyurea. Furthermore, the inhibition of replicative synthesis by the carcinogens was accompanied by marked stimulation of deoxyribonucleic acid repair synthesis. Concomitant measurement of replicative and repair synthesis appears to be an effective approach for the in vitro study of carcinogen-induced damage in the deoxyribonucleic acid of proliferating lymphoid cells."}
{"id": "PMID:215303", "title": "Heterotransplantation into nude mice of pancreatic carcinoma induced by N-bis(2-hydroxypropyl)nitrosamine in hamsters.", "content": "Heterotransplantation into nude mice by the subcutaneous (s.c.) and intraperitoneal (i.p.) routes of hamster pancreatic ductal cell carcinomas induced by N-bis(2-hydroxypropyl)nitrosamine (DHPN) was studied. By s.c. transplantation, tumors occurred in 1 of 4 mice at the first trial, and the tumor incidence was 100% for shorter periods by serial transfer. By i.p. transplantation, the malignant potential of hamster pancreatic ductal cell carcinoma was expressed as intra-abdominal invasive tumors with bloody ascites (carcinomatous peritonitis). Tumors in nude mice basically retained the histology of the original hamster pancreatic ductal cell carcinoma.", "contents": "Heterotransplantation into nude mice of pancreatic carcinoma induced by N-bis(2-hydroxypropyl)nitrosamine in hamsters. Heterotransplantation into nude mice by the subcutaneous (s.c.) and intraperitoneal (i.p.) routes of hamster pancreatic ductal cell carcinomas induced by N-bis(2-hydroxypropyl)nitrosamine (DHPN) was studied. By s.c. transplantation, tumors occurred in 1 of 4 mice at the first trial, and the tumor incidence was 100% for shorter periods by serial transfer. By i.p. transplantation, the malignant potential of hamster pancreatic ductal cell carcinoma was expressed as intra-abdominal invasive tumors with bloody ascites (carcinomatous peritonitis). Tumors in nude mice basically retained the histology of the original hamster pancreatic ductal cell carcinoma."}
{"id": "PMID:215304", "title": "Preliminary results of combined surgery and adjuvant Bacillus Calmette-Gu\u00e9rin plus levamisole treatment of resectable lung cancer.", "content": "The administration of intrapleural bacillus Calmette-Gu\u00e9rin (BCG) alone and intrapleural BCG plus levamisole was compared to placebo in patients with resectable, non-small cell cancer of the lung. This report is based on an interim analysis of 100 eligible patients with a median followup of 245 days. No significant treatment effects are apparent at the present time, although current trends are consistent with an approximate 30% reduction in recurrence rate in patients receiving intrapleural BCG. There is little evidence to suggest that the addition of levamisole will contribute to this effect. A relationship between purified protein derivative conversion and tumor recurrence is apparent. Failure to manifest purified protein derivative conversion following administration of intrapleural BCG is associated with a significantly greater risk of tumor recurrence.", "contents": "Preliminary results of combined surgery and adjuvant Bacillus Calmette-Gu\u00e9rin plus levamisole treatment of resectable lung cancer. The administration of intrapleural bacillus Calmette-Gu\u00e9rin (BCG) alone and intrapleural BCG plus levamisole was compared to placebo in patients with resectable, non-small cell cancer of the lung. This report is based on an interim analysis of 100 eligible patients with a median followup of 245 days. No significant treatment effects are apparent at the present time, although current trends are consistent with an approximate 30% reduction in recurrence rate in patients receiving intrapleural BCG. There is little evidence to suggest that the addition of levamisole will contribute to this effect. A relationship between purified protein derivative conversion and tumor recurrence is apparent. Failure to manifest purified protein derivative conversion following administration of intrapleural BCG is associated with a significantly greater risk of tumor recurrence."}
{"id": "PMID:215305", "title": "Overview of thymosin activity.", "content": "Our current research program centers around the biologic and chemical characterization of the family of polypeptides present in thymosin fraction 5. A system of nomenclature has been developed and the peptides are being systematically isolated and chemically characterized. Thymosin fraction 5 and its component parts influence a variety of lymphocyte properties including cyclic nucleotide levels, migration inhibitory factor production, T-dependent antibody production, and expression of certain surface markers. Thymosin is being used in clinical trials to investigate its effects on immunodeficiency diseases, malignant diseases, and autoimmune diseases.", "contents": "Overview of thymosin activity. Our current research program centers around the biologic and chemical characterization of the family of polypeptides present in thymosin fraction 5. A system of nomenclature has been developed and the peptides are being systematically isolated and chemically characterized. Thymosin fraction 5 and its component parts influence a variety of lymphocyte properties including cyclic nucleotide levels, migration inhibitory factor production, T-dependent antibody production, and expression of certain surface markers. Thymosin is being used in clinical trials to investigate its effects on immunodeficiency diseases, malignant diseases, and autoimmune diseases."}
{"id": "PMID:215306", "title": "Experiences with thymosin in primary immunodeficiency disease.", "content": "Thymosin has no effect in vitro on cyclic AMP levels in thymocytes. However, when thymosin was injected into patients lacking \"serum factor\" (SF) activity, it induced the appearance of SF or SF-like activity and the disappearance of target cells for SF among the peripheral blood lymphocytes of the treated patients. On the other hand, when thymosin was injected into one patient with normal SF activity, it induced a marked decrease of SF activity and the appearance of target cells for SF among the peripheral blood lymphocytes of this particular patient.", "contents": "Experiences with thymosin in primary immunodeficiency disease. Thymosin has no effect in vitro on cyclic AMP levels in thymocytes. However, when thymosin was injected into patients lacking \"serum factor\" (SF) activity, it induced the appearance of SF or SF-like activity and the disappearance of target cells for SF among the peripheral blood lymphocytes of the treated patients. On the other hand, when thymosin was injected into one patient with normal SF activity, it induced a marked decrease of SF activity and the appearance of target cells for SF among the peripheral blood lymphocytes of this particular patient."}
{"id": "PMID:215307", "title": "Thymosin in cancer patients: in vitro effects and correlations with clinical response to thymosin immunotherapy.", "content": "Studies on the effect of thymosin on T-cell levels in vitro among normal persons and cancer patients show that, in general, T-cell levels increase after incubation with thymosin in populations with low initial T-cell levels while the levels decrease in populations with high initial T-cell levels. In patients with small cell carcinoma of the lung receiving intensive chemotherapy also randomized to receive thymosin at a dose of 60 mg/m2, thymosin at a dose of 20 mg/m2, or placebo twice weekly, increased survival occurred in patients receiving the thymosin dose of 60 mg/m2. The increase in survival was greatest in patients with low pretreatment T-cell and alpha2HS-glycoprotein levels. These observations suggest that the cancer patients most likely to benefit therapeutically from adjuvant treatment with thymosin are those with relatively low initial T-cell levels and other parameters of cellular immunity.", "contents": "Thymosin in cancer patients: in vitro effects and correlations with clinical response to thymosin immunotherapy. Studies on the effect of thymosin on T-cell levels in vitro among normal persons and cancer patients show that, in general, T-cell levels increase after incubation with thymosin in populations with low initial T-cell levels while the levels decrease in populations with high initial T-cell levels. In patients with small cell carcinoma of the lung receiving intensive chemotherapy also randomized to receive thymosin at a dose of 60 mg/m2, thymosin at a dose of 20 mg/m2, or placebo twice weekly, increased survival occurred in patients receiving the thymosin dose of 60 mg/m2. The increase in survival was greatest in patients with low pretreatment T-cell and alpha2HS-glycoprotein levels. These observations suggest that the cancer patients most likely to benefit therapeutically from adjuvant treatment with thymosin are those with relatively low initial T-cell levels and other parameters of cellular immunity."}
{"id": "PMID:215308", "title": "Wilms' tumor--model of a curable pediatric malignant solid tumor.", "content": "Wilms' tumor is the model of the treatment of a pediatric solid tumor. Initially it appeared that multi-modality therapy, consisting of transabodominal nephrectomy, post-operative radiation therapy to the tumor bed and adjuvant, single agent chemotherapy provided the highest likelihood of disease-free survival. The identification of important prognostic factors, such as histology, tumor weight, lymph node involvement and age at diagnosis has led to a re-examination of the treatment of Wilms' tumor. Future therapeutic developments will include the administration of less therapy to some well defined groups of patients, and the exploration of new programs for patients who have been demonstrated to have a poor prognosis using currently accepted treatment techniques.", "contents": "Wilms' tumor--model of a curable pediatric malignant solid tumor. Wilms' tumor is the model of the treatment of a pediatric solid tumor. Initially it appeared that multi-modality therapy, consisting of transabodominal nephrectomy, post-operative radiation therapy to the tumor bed and adjuvant, single agent chemotherapy provided the highest likelihood of disease-free survival. The identification of important prognostic factors, such as histology, tumor weight, lymph node involvement and age at diagnosis has led to a re-examination of the treatment of Wilms' tumor. Future therapeutic developments will include the administration of less therapy to some well defined groups of patients, and the exploration of new programs for patients who have been demonstrated to have a poor prognosis using currently accepted treatment techniques."}
{"id": "PMID:215310", "title": "Immunologic localization of alpha- and beta-endorphins and beta-lipotropin in corticotropic cells of the normal and anencephalic fetal pituitaries.", "content": "The use of antibodies to alpha-(17--39) ACTH, beta-LPH, and alpha- and beta-endorphins has enabled the detection of immunoreactive cells as early as the eight week of fetal life. Immunoreactive cells are located in the anterior and intermediate lobes of the pituitary gland in normal human fetuses. The same cells reacted with different antisera used in the present study. No immunoreactive cells were observed in the posterior lobe. The specificity of the immunocytological reaction has been controlled. In seven anencephalic fetuses, the presence of immunoreactive cells suggests that ACTH and beta-LPH can originate from a common precursor and are synthesized independent of the hypothalamus.", "contents": "Immunologic localization of alpha- and beta-endorphins and beta-lipotropin in corticotropic cells of the normal and anencephalic fetal pituitaries. The use of antibodies to alpha-(17--39) ACTH, beta-LPH, and alpha- and beta-endorphins has enabled the detection of immunoreactive cells as early as the eight week of fetal life. Immunoreactive cells are located in the anterior and intermediate lobes of the pituitary gland in normal human fetuses. The same cells reacted with different antisera used in the present study. No immunoreactive cells were observed in the posterior lobe. The specificity of the immunocytological reaction has been controlled. In seven anencephalic fetuses, the presence of immunoreactive cells suggests that ACTH and beta-LPH can originate from a common precursor and are synthesized independent of the hypothalamus."}
{"id": "PMID:215311", "title": "Intranuclear inclusions in the developing neurons of the rat cuneate nuclei.", "content": "The ultrastructure of intranuclear rodlets, microtubules, fibrillar lattices and membranous inclusions found in the developing cuneate nuclei of rats is described. Rodlets, ranging in diameter from 96--312 nm and in length from 1--2 micrometer, are made up of tightly packed straight filaments measuring 5--8 nm in diameter. Microtubules with a diameter of 26 nm are clustered together. Fibrillar lattices are made up of fibrils with a diameter of 9 nm arranged in layers or sets. Two to nine sets make up a lattice, with a maximum width of 68 nm, in which the adjacent sets are arranged at an angle to each other. Rodlets and fibrillar lattices occur in 6.8% of the neurons. Membranous inclusions, reported here for the first time in normal neurons, are of 2 types: small vesicles of 0.1--0.6 micrometer and large vacuoles measuring 1--2 micrometer. Both types are bounded by either a single or a double membrane and generally have an electron lucent content. Membranous inclusions occur in 25.3% of the neurons. Changes in the frequency of occurrence of the various intranuclear inclusions in the course of postnatal development are also reported.", "contents": "Intranuclear inclusions in the developing neurons of the rat cuneate nuclei. The ultrastructure of intranuclear rodlets, microtubules, fibrillar lattices and membranous inclusions found in the developing cuneate nuclei of rats is described. Rodlets, ranging in diameter from 96--312 nm and in length from 1--2 micrometer, are made up of tightly packed straight filaments measuring 5--8 nm in diameter. Microtubules with a diameter of 26 nm are clustered together. Fibrillar lattices are made up of fibrils with a diameter of 9 nm arranged in layers or sets. Two to nine sets make up a lattice, with a maximum width of 68 nm, in which the adjacent sets are arranged at an angle to each other. Rodlets and fibrillar lattices occur in 6.8% of the neurons. Membranous inclusions, reported here for the first time in normal neurons, are of 2 types: small vesicles of 0.1--0.6 micrometer and large vacuoles measuring 1--2 micrometer. Both types are bounded by either a single or a double membrane and generally have an electron lucent content. Membranous inclusions occur in 25.3% of the neurons. Changes in the frequency of occurrence of the various intranuclear inclusions in the course of postnatal development are also reported."}
{"id": "PMID:215312", "title": "Intranuclear rodlets in woodchuck thyroid follicular cells.", "content": "Intranuclear rodlets are seen in thyroid follicular cells of woodchucks fixed during summer and fall. They are not observed in winter and spring animals. A functional significance of these structures is suggested.", "contents": "Intranuclear rodlets in woodchuck thyroid follicular cells. Intranuclear rodlets are seen in thyroid follicular cells of woodchucks fixed during summer and fall. They are not observed in winter and spring animals. A functional significance of these structures is suggested."}
{"id": "PMID:215313", "title": "An immunohistochemical study of epithelial cells in the posterior lobe and pars tuberalis of the human adult pituitary gland.", "content": "Pituitary glands were examined using reference staining (hematoxylin and eosin, periodic acid-Schiff and alcian blue) and the peroxidase-labeled antibody method, for 1) \"invading\" anterior cells in the posterior lobe, 2) intermediate colloid forming follicles, and 3) pars tuberalis cells. The results showed: 1) that the majority of cases possessed \"invading\" anterior cells of various amount. Most of these cells were positive for ACTH1-18, ACTH17-39 and betaMSH. However, on a few occasions, scattered GH, PRL, FSHalpha, FSHbeta, LHbeta and even TSHbeta cells were also present. 2) Colloid forming follicular cells were mostly ACTH cells, but also contained occasional other hormone-secreting cells. Hormone negative cells were correlated with salivary type epithelium. Well established acinic type salivary glands and ciliated epithelium were negative for any hormones immunohistochemically. 3) Pars tuberalis cells were predominantly gonadotrophs but also included TSHbeta and ACTH cells. Some cells appeared to contain both FSHbeta and LHbeta. When these cells underwent squamous metaplasia, they seemed to lose their hormone secreting activity.", "contents": "An immunohistochemical study of epithelial cells in the posterior lobe and pars tuberalis of the human adult pituitary gland. Pituitary glands were examined using reference staining (hematoxylin and eosin, periodic acid-Schiff and alcian blue) and the peroxidase-labeled antibody method, for 1) \"invading\" anterior cells in the posterior lobe, 2) intermediate colloid forming follicles, and 3) pars tuberalis cells. The results showed: 1) that the majority of cases possessed \"invading\" anterior cells of various amount. Most of these cells were positive for ACTH1-18, ACTH17-39 and betaMSH. However, on a few occasions, scattered GH, PRL, FSHalpha, FSHbeta, LHbeta and even TSHbeta cells were also present. 2) Colloid forming follicular cells were mostly ACTH cells, but also contained occasional other hormone-secreting cells. Hormone negative cells were correlated with salivary type epithelium. Well established acinic type salivary glands and ciliated epithelium were negative for any hormones immunohistochemically. 3) Pars tuberalis cells were predominantly gonadotrophs but also included TSHbeta and ACTH cells. Some cells appeared to contain both FSHbeta and LHbeta. When these cells underwent squamous metaplasia, they seemed to lose their hormone secreting activity."}
{"id": "PMID:215315", "title": "Schwann cell growth factors.", "content": "Purified rat Schwann cells were found to proliferate very slowly in normal growth medium containing 10% fetal calf serum (FCS). Crude extracts of bovine pituitary or brain markedly enhanced Schwann cell growth, while similar extracts of nerve roots, liver and kidney did not. Pituitary extracts were more potent than brain extracts, and extracts from both anterior and posterior pituitary were active. The mitogenic activity of pituitary extracts was reduced by treatment with trypsin, and abolished by pronase and by boiling. A variety of known anterior and posterior pituitary hormones, as well as fibroblast, epidermal and nerve growth factors, were not mitogenic. FCS (greater than 1%) was required for Schwann cell proliferation, but even high concentrations of FCS did not substitute for pituitary or brain extracts, and serum from various other species did not support Schwann cell growth. Although various agents that increase cyclic AMP levels (such as cholera toxin) had been shown to be Schwann cell mitogens, extracts of pituitary or brain did not increase cyclic AMP levels. Extracts of various bovine tissues, including pituitary, brain, liver and kidney, acted synergistically with cholera toxin in stimulating Schwann cell proliferation, although the increase in cyclic AMP induced by the mixture was not greater than that seen with cholera toxin alone. We conclude that there are at least two separate pathways for stimulating Schwann cell division, only one of which involves an increase in intracellular cyclic AMP.", "contents": "Schwann cell growth factors. Purified rat Schwann cells were found to proliferate very slowly in normal growth medium containing 10% fetal calf serum (FCS). Crude extracts of bovine pituitary or brain markedly enhanced Schwann cell growth, while similar extracts of nerve roots, liver and kidney did not. Pituitary extracts were more potent than brain extracts, and extracts from both anterior and posterior pituitary were active. The mitogenic activity of pituitary extracts was reduced by treatment with trypsin, and abolished by pronase and by boiling. A variety of known anterior and posterior pituitary hormones, as well as fibroblast, epidermal and nerve growth factors, were not mitogenic. FCS (greater than 1%) was required for Schwann cell proliferation, but even high concentrations of FCS did not substitute for pituitary or brain extracts, and serum from various other species did not support Schwann cell growth. Although various agents that increase cyclic AMP levels (such as cholera toxin) had been shown to be Schwann cell mitogens, extracts of pituitary or brain did not increase cyclic AMP levels. Extracts of various bovine tissues, including pituitary, brain, liver and kidney, acted synergistically with cholera toxin in stimulating Schwann cell proliferation, although the increase in cyclic AMP induced by the mixture was not greater than that seen with cholera toxin alone. We conclude that there are at least two separate pathways for stimulating Schwann cell division, only one of which involves an increase in intracellular cyclic AMP."}
{"id": "PMID:215316", "title": "Immunocytochemical visualization of coated pits and vesicles in human fibroblasts: relation to low density lipoprotein receptor distribution.", "content": "The coated pit-coated vesicle system has a key role in the uptake of plasma low density lipoprotein (LDL) and other receptor-bound proteins in human fibroblasts. To study the distribution of coated pits and coated vesicles in fibroblasts by immunochemical techniques at both the light and electron microscopic levels, we immunized rabbits with coat protein extracted from bovine brain-coated vesicles. The resulting anti-coat protein antibody was directed predominantly against clathrin, the 180,ooo dalton protein that constitutes the major component of coat protein. By indirect immunoperoxidase electron microscopy, the anti-coat protein antibody was observed to bind specifically to coated pits on the surface of human fibroblasts and to coated vesicles within the cell. Indirect immunofluorescence and immunoperoxidase staining techniques at the light microscopic level revealed that the coat protein was distributed in fibroblasts in two distinctive patterns: as discrete foci on or near the cell surface that were linearly aligned in association with phase-dense cellular fibers (first pattern), and as intracellular foci that were randomly arranged around the cell nucleus (second pattern). The distribution of coat protein in fibroblasts was compared with the distribution of ferritin-labeled LDL, which was studied with the use of similar electron microscopic and immunofluorescence techniques. As previously reported, electron microscopic studies revealed that the LDL-ferritin binding sites at 4 degrees C were clustered in coated pits. By immunofluorescence microscopy, the LDL-ferritin that was bound to receptors within coated pits was shown to be arranged linearly over the cell surface in a pattern that was similar to the linear arrangement of coat protein (first pattern). Considered together, the current data indicate that coated pits in human fibroblasts contain a protein analogous to clathrin, and that those coated pits which contain receptors for LDL are located over intracellular fibers most likely corresponding to stress fibers. These observationa may have relevance to the mechanisms by which the coated pit-coated vesicle system efficiently delivers recptor-bound ligands to lysosomes.", "contents": "Immunocytochemical visualization of coated pits and vesicles in human fibroblasts: relation to low density lipoprotein receptor distribution. The coated pit-coated vesicle system has a key role in the uptake of plasma low density lipoprotein (LDL) and other receptor-bound proteins in human fibroblasts. To study the distribution of coated pits and coated vesicles in fibroblasts by immunochemical techniques at both the light and electron microscopic levels, we immunized rabbits with coat protein extracted from bovine brain-coated vesicles. The resulting anti-coat protein antibody was directed predominantly against clathrin, the 180,ooo dalton protein that constitutes the major component of coat protein. By indirect immunoperoxidase electron microscopy, the anti-coat protein antibody was observed to bind specifically to coated pits on the surface of human fibroblasts and to coated vesicles within the cell. Indirect immunofluorescence and immunoperoxidase staining techniques at the light microscopic level revealed that the coat protein was distributed in fibroblasts in two distinctive patterns: as discrete foci on or near the cell surface that were linearly aligned in association with phase-dense cellular fibers (first pattern), and as intracellular foci that were randomly arranged around the cell nucleus (second pattern). The distribution of coat protein in fibroblasts was compared with the distribution of ferritin-labeled LDL, which was studied with the use of similar electron microscopic and immunofluorescence techniques. As previously reported, electron microscopic studies revealed that the LDL-ferritin binding sites at 4 degrees C were clustered in coated pits. By immunofluorescence microscopy, the LDL-ferritin that was bound to receptors within coated pits was shown to be arranged linearly over the cell surface in a pattern that was similar to the linear arrangement of coat protein (first pattern). Considered together, the current data indicate that coated pits in human fibroblasts contain a protein analogous to clathrin, and that those coated pits which contain receptors for LDL are located over intracellular fibers most likely corresponding to stress fibers. These observationa may have relevance to the mechanisms by which the coated pit-coated vesicle system efficiently delivers recptor-bound ligands to lysosomes."}
{"id": "PMID:215317", "title": "The entry into host cells of Sindbis virus, vesicular stomatitis virus and Sendai virus.", "content": "We have compared the mechanisms of entry into host cells of three enveloped viruses: Sendai virus, vesicular stomatitis virus (VSV) and Sindbis virus. Virus entry by membrane fusion should antigenically modify the surface of a newly infected cell in such a way that it will be killed by anti-viral antibody and complement. On the other hand, virus entry by a mechanism involving uptake by the cell of the whole virion should not make cells sensitive to antibody and complement. As expected, cells newly infected with Sendai virus were readily and completely lysed by anti-Sendai antibody and complement. In marked contrast, however, cells newly infected with either Sindbis virus or VSV were killed by anti-viral antibody and complement only when infected at an extremely high multiplicity of infection, in excess of 1000 plaque-forming units per cell. We favor the following explanation for these results with Sindbis virus and VSV: a very large majority of the Sindbis and VSV virions entered the infected cells by some means other than membrane fusion, presumably engulfment of the whole particle. Efficient entry by way of membrane fusion may therefore not be a general characteristic of enveloped viruses.", "contents": "The entry into host cells of Sindbis virus, vesicular stomatitis virus and Sendai virus. We have compared the mechanisms of entry into host cells of three enveloped viruses: Sendai virus, vesicular stomatitis virus (VSV) and Sindbis virus. Virus entry by membrane fusion should antigenically modify the surface of a newly infected cell in such a way that it will be killed by anti-viral antibody and complement. On the other hand, virus entry by a mechanism involving uptake by the cell of the whole virion should not make cells sensitive to antibody and complement. As expected, cells newly infected with Sendai virus were readily and completely lysed by anti-Sendai antibody and complement. In marked contrast, however, cells newly infected with either Sindbis virus or VSV were killed by anti-viral antibody and complement only when infected at an extremely high multiplicity of infection, in excess of 1000 plaque-forming units per cell. We favor the following explanation for these results with Sindbis virus and VSV: a very large majority of the Sindbis and VSV virions entered the infected cells by some means other than membrane fusion, presumably engulfment of the whole particle. Efficient entry by way of membrane fusion may therefore not be a general characteristic of enveloped viruses."}
{"id": "PMID:215318", "title": "Transformation of hamster embryo fibroblasts by a specific fragment of the herpes simplex virus genome.", "content": "Isolated restriction endonuclease fragments of the herpes simplex virus type 1 (HSV-1) genome were introduced into hamster embryo cells to identify DNA sequences capable to transforming the cells with respect to acquisition of properties correlated with tumorigenicity. One of the fragments generated by cleavage of HSV-1 DNA with the restriction endonuclease Xba I was found to induce transformation at a frequency of about 10 colonies per quantity of fragment recovered from 1 microgram of uncut DNA; fractions containing the other Xba I fragments failed to induce transformation reproducibly, although occasional colonies were detected. The fragment with transforming activity (Xba I-F) is 15.5 X 10(6) daltons in molecular weight and is located between 0.30 and 0.45 map units on the HSV-1 genome. The Xba I-F transformants obtained were selected for their ability to replicate in low concentrations of serum; in addition, they were found to attain high saturation densities in the presence of 10% serum and to form colonies in semisolid medium. Moreover, the transformed cells produced at least one of the viral gene products (a membrane glycoprotein) encoded in the fragment used for transformation, indicating not only that viral DNA was incorporated into the cells, but also that viral genes were expressed.", "contents": "Transformation of hamster embryo fibroblasts by a specific fragment of the herpes simplex virus genome. Isolated restriction endonuclease fragments of the herpes simplex virus type 1 (HSV-1) genome were introduced into hamster embryo cells to identify DNA sequences capable to transforming the cells with respect to acquisition of properties correlated with tumorigenicity. One of the fragments generated by cleavage of HSV-1 DNA with the restriction endonuclease Xba I was found to induce transformation at a frequency of about 10 colonies per quantity of fragment recovered from 1 microgram of uncut DNA; fractions containing the other Xba I fragments failed to induce transformation reproducibly, although occasional colonies were detected. The fragment with transforming activity (Xba I-F) is 15.5 X 10(6) daltons in molecular weight and is located between 0.30 and 0.45 map units on the HSV-1 genome. The Xba I-F transformants obtained were selected for their ability to replicate in low concentrations of serum; in addition, they were found to attain high saturation densities in the presence of 10% serum and to form colonies in semisolid medium. Moreover, the transformed cells produced at least one of the viral gene products (a membrane glycoprotein) encoded in the fragment used for transformation, indicating not only that viral DNA was incorporated into the cells, but also that viral genes were expressed."}
{"id": "PMID:215320", "title": "Progesterone-induced meiosis in Xenopus laevis oocytes: a role for cAMP at the \"maturation-promoting factor\" level.", "content": "Cholera toxin inhibition of progesterone-induced meiosis of Xenopus laevis oocytes in vitro has been correlated with increased cAMP levels. Inhibition of germinal vesicle breakdown (Gvbd) and cAMP increase occurred after a lag period of 2 hr, when cholera toxin was injected, or 4--5 hr, when applied externally. The ability of the maturation-promoting factor (Mpf) to provoke Gvbd when injected into recipient oocytes was found to be dependent upon whether the oocytes had been exposed to cholera toxin alone or to toxin and progesterone. With the former, cAMP levels were elevated and Mpf activity was abolished, whereas with the latter, the increase in cAMP was less pronounced and Mpf activity was observed. Injection of cAMP or its 8-thio derivatives shortly before the appearance of progesterone-induced Mpf abolished Gvbd. If injected earlier or later, no inhibition was observed. In contrast, cholera toxin inhibited maturation even when added several hours before progesterone, suggesting a sustained accumulation of cAMP. No Gvbd occurred when 8-thio-methyl-cAMP was injected together with Mpf. These data suggest that cAMP is involved in the control of the formation/amplification and/or activity of Mpf-a result which may be of general significance in cell division mechanisms.", "contents": "Progesterone-induced meiosis in Xenopus laevis oocytes: a role for cAMP at the \"maturation-promoting factor\" level. Cholera toxin inhibition of progesterone-induced meiosis of Xenopus laevis oocytes in vitro has been correlated with increased cAMP levels. Inhibition of germinal vesicle breakdown (Gvbd) and cAMP increase occurred after a lag period of 2 hr, when cholera toxin was injected, or 4--5 hr, when applied externally. The ability of the maturation-promoting factor (Mpf) to provoke Gvbd when injected into recipient oocytes was found to be dependent upon whether the oocytes had been exposed to cholera toxin alone or to toxin and progesterone. With the former, cAMP levels were elevated and Mpf activity was abolished, whereas with the latter, the increase in cAMP was less pronounced and Mpf activity was observed. Injection of cAMP or its 8-thio derivatives shortly before the appearance of progesterone-induced Mpf abolished Gvbd. If injected earlier or later, no inhibition was observed. In contrast, cholera toxin inhibited maturation even when added several hours before progesterone, suggesting a sustained accumulation of cAMP. No Gvbd occurred when 8-thio-methyl-cAMP was injected together with Mpf. These data suggest that cAMP is involved in the control of the formation/amplification and/or activity of Mpf-a result which may be of general significance in cell division mechanisms."}
{"id": "PMID:215321", "title": "Metabolism of acetylcholine receptor in chick embryo muscle cells: effects of RSV and PMA.", "content": "We have investigated some aspects of the metabolism of the integral membrane protein acetylcholine receptor (AChR) in normal and transformed cultures of chick embryo muscle cells. Turnover of AChR in control muscle cell cultures was compared with turnover in cultures infected and transformed by a temperature-sensitive mutant of Rous sarcoma virus (RSV) and with cultures treated with the tumor promoter phorbol myristate acetate (PMA). The parameters of AChR metabolism were estimated using 125I-alpha-bungarotoxin as a stoichiometric high affinity ligand for the AChR. We found that both RSV transformation and PMA increased the rate of degradation and decreased the rate of synthesis of AChR. The consequent reduction in steady state receptor levels suggests that oncogenic transformation and tumor promoter significantly alter the metabolism of cell surface membranes. We also observed that parameters of AChR metabolism in control cultures changed systematically in a pattern which depended upon the age of the culture as well as the use of embryo extract or fetal bovine serum as medium supplements. The muscle cell system allows quantitative measurement of an integral membrane protein and its metabolism, and may serve as a more general model for alterations in membrane and surface receptor metabolism associated with the transformed state.", "contents": "Metabolism of acetylcholine receptor in chick embryo muscle cells: effects of RSV and PMA. We have investigated some aspects of the metabolism of the integral membrane protein acetylcholine receptor (AChR) in normal and transformed cultures of chick embryo muscle cells. Turnover of AChR in control muscle cell cultures was compared with turnover in cultures infected and transformed by a temperature-sensitive mutant of Rous sarcoma virus (RSV) and with cultures treated with the tumor promoter phorbol myristate acetate (PMA). The parameters of AChR metabolism were estimated using 125I-alpha-bungarotoxin as a stoichiometric high affinity ligand for the AChR. We found that both RSV transformation and PMA increased the rate of degradation and decreased the rate of synthesis of AChR. The consequent reduction in steady state receptor levels suggests that oncogenic transformation and tumor promoter significantly alter the metabolism of cell surface membranes. We also observed that parameters of AChR metabolism in control cultures changed systematically in a pattern which depended upon the age of the culture as well as the use of embryo extract or fetal bovine serum as medium supplements. The muscle cell system allows quantitative measurement of an integral membrane protein and its metabolism, and may serve as a more general model for alterations in membrane and surface receptor metabolism associated with the transformed state."}
{"id": "PMID:215322", "title": "Plasminogen activator in chick embryo muscle cells: induction of enzyme by RSV, PMA and retinoic acid.", "content": "To explore the generality of the effects of sarcoma viruses, tumor-promoting phorbol esters and retinoic acid, we have studied plasminogen activator production in differentiating chick myogenic cultures. Although slightly higher than in chick fibroblast cultures, the level of spontaneously synthesized enzyme is low; it reaches a peak shortly after maximum cell fusion has been completed and then declines. Rous sarcoma virus (RSV) transformation of differentiating myotubes was accomplished by infecting myoblasts with a temperature-sensitive mutant, maintaining cultures at the nonpermissive temperature until completion of fusion and shifting to permissive temperatures at selected times thereafter. RSV transformation, phorbol myristate acetate (PMA) and retinoic acid all induced high levels of plasminogen activator production by differentiating myotubes in the absence of DNA synthesis. In comparison with fibroblasts, virus-induced enzyme synthesis by myogenic cultures proceeded more slowly but ultimately reached comparably high levels. Whereas cAMP strongly repressed RSV- and PMA-induced plasminogen activator production by chick fibroblasts, it weakly stimulated enzyme synthesis by myotubes. This suggests that enzyme induction by RSV and PMA is not mediated primarily through effects on cAMP metabolism.", "contents": "Plasminogen activator in chick embryo muscle cells: induction of enzyme by RSV, PMA and retinoic acid. To explore the generality of the effects of sarcoma viruses, tumor-promoting phorbol esters and retinoic acid, we have studied plasminogen activator production in differentiating chick myogenic cultures. Although slightly higher than in chick fibroblast cultures, the level of spontaneously synthesized enzyme is low; it reaches a peak shortly after maximum cell fusion has been completed and then declines. Rous sarcoma virus (RSV) transformation of differentiating myotubes was accomplished by infecting myoblasts with a temperature-sensitive mutant, maintaining cultures at the nonpermissive temperature until completion of fusion and shifting to permissive temperatures at selected times thereafter. RSV transformation, phorbol myristate acetate (PMA) and retinoic acid all induced high levels of plasminogen activator production by differentiating myotubes in the absence of DNA synthesis. In comparison with fibroblasts, virus-induced enzyme synthesis by myogenic cultures proceeded more slowly but ultimately reached comparably high levels. Whereas cAMP strongly repressed RSV- and PMA-induced plasminogen activator production by chick fibroblasts, it weakly stimulated enzyme synthesis by myotubes. This suggests that enzyme induction by RSV and PMA is not mediated primarily through effects on cAMP metabolism."}
{"id": "PMID:215323", "title": "Kinase-negative mutants of S49 mouse lymphoma cells carry a trans-dominant mutation affecting expression of cAMP-dependent protein kinase.", "content": "Kinase-negative mutants of S49 mouse lymphoma cells are pleiotropically negative for all known cAMP-mediated responses of S49 cells and yield cell extracts which are deficient in cAMP binding activity and devoid of cAMP-dependent protein kinase activity. In hybrids between kinase-negative and wild-type cells, the mutant phenotype is dominant: the tetraploid hybrids have reduced cAMP-binding activity and undetectable cAMP-dependent kinase activity. The mutant phenotype is attributable to neither a soluble inhibitor of kinase catalytic subunit, nor a defective kinase regulatory subunit acting as an inhibitor, nor a defective catalytic subunit which sequesters regulatory subunits in inactive complexes. We propose that these mutants carry trans-dominant lesions in a regulatory locus responsible for setting intracellular levels of kinase expression.", "contents": "Kinase-negative mutants of S49 mouse lymphoma cells carry a trans-dominant mutation affecting expression of cAMP-dependent protein kinase. Kinase-negative mutants of S49 mouse lymphoma cells are pleiotropically negative for all known cAMP-mediated responses of S49 cells and yield cell extracts which are deficient in cAMP binding activity and devoid of cAMP-dependent protein kinase activity. In hybrids between kinase-negative and wild-type cells, the mutant phenotype is dominant: the tetraploid hybrids have reduced cAMP-binding activity and undetectable cAMP-dependent kinase activity. The mutant phenotype is attributable to neither a soluble inhibitor of kinase catalytic subunit, nor a defective kinase regulatory subunit acting as an inhibitor, nor a defective catalytic subunit which sequesters regulatory subunits in inactive complexes. We propose that these mutants carry trans-dominant lesions in a regulatory locus responsible for setting intracellular levels of kinase expression."}
{"id": "PMID:215324", "title": "Mapping unintegrated avian sarcoma virus DNA: termini of linear DNA bear 300 nucleotides present once or twice in two species of circular DNA.", "content": "Three major species of viral DNA have been observed in cells infected by retroviruses: a linear, double-stranded copy of a subunit of viral RNA; closed circular DNA; and proviral DNA inserted covalently into the genome of the host cell. We have studied the structures of the unintegrated forms of avian sarcoma virus (ASA) DNA using agarose gel electrophoresis in conjunction with restriction endonucleases and molecular hybridization techniques. The linear duplex DNA is approximately the same length as a subunit of viral RNA (approximately 10 kb) and it bears natural repeats of approximately 300 nucleotides at its termini. The repeats are composed of sequences derived from both the 3' and 5' termini of viral RNA in a manner suggesting that the viral DNA polymerase is transferred twice between templates. Thus the first end begins with a sequence from the 5' terminus of viral RNA and is permuted by about 100 nucleotides with respect to the 3' terminus of viral RNA; the linear DNA terminates with a sequence of about 200 nucleotides derived from the 3' end of viral RNA. We represent this structure, synthesized from right to left, as 3'5'-----3'5'. Two closed circular species of approximately monomeric size have been identified. The less abundant species contain all the sequences identified in linear DNA, including two copies in tandem of the 300 nucleotide 3'5' repeat. The major species lacks about 300 base pairs (bp) mapped to the region of the repeated sequence; thus it presumably contains only a single copy of that sequence. The strategies used to determine these structures involved the assignment of over 20 cleavage sites for restriction endonucleases on the physical maps of ASV DNA. Several strains of ASV were compared with respect to these sites, and the sites have been located in relation to deletions frequently observed in the env and src genes of ASV.", "contents": "Mapping unintegrated avian sarcoma virus DNA: termini of linear DNA bear 300 nucleotides present once or twice in two species of circular DNA. Three major species of viral DNA have been observed in cells infected by retroviruses: a linear, double-stranded copy of a subunit of viral RNA; closed circular DNA; and proviral DNA inserted covalently into the genome of the host cell. We have studied the structures of the unintegrated forms of avian sarcoma virus (ASA) DNA using agarose gel electrophoresis in conjunction with restriction endonucleases and molecular hybridization techniques. The linear duplex DNA is approximately the same length as a subunit of viral RNA (approximately 10 kb) and it bears natural repeats of approximately 300 nucleotides at its termini. The repeats are composed of sequences derived from both the 3' and 5' termini of viral RNA in a manner suggesting that the viral DNA polymerase is transferred twice between templates. Thus the first end begins with a sequence from the 5' terminus of viral RNA and is permuted by about 100 nucleotides with respect to the 3' terminus of viral RNA; the linear DNA terminates with a sequence of about 200 nucleotides derived from the 3' end of viral RNA. We represent this structure, synthesized from right to left, as 3'5'-----3'5'. Two closed circular species of approximately monomeric size have been identified. The less abundant species contain all the sequences identified in linear DNA, including two copies in tandem of the 300 nucleotide 3'5' repeat. The major species lacks about 300 base pairs (bp) mapped to the region of the repeated sequence; thus it presumably contains only a single copy of that sequence. The strategies used to determine these structures involved the assignment of over 20 cleavage sites for restriction endonucleases on the physical maps of ASV DNA. Several strains of ASV were compared with respect to these sites, and the sites have been located in relation to deletions frequently observed in the env and src genes of ASV."}
{"id": "PMID:215325", "title": "Proviruses of avian sarcoma virus are terminally redundant, co-extensive with unintegrated linear DNA and integrated at many sites.", "content": "We have analyzed the DNA from 15 clones of avian sarcoma virus (ASV)-transformed rat cells with restriction endonucleases and molecular hybridization techniques to determine the location and structure of proviral DNA. All twenty units of proviral DNA identified in these 15 clones appear to be inserted at different sites in host DNA. In each of the ten cases that could be sufficiently well mapped, entirely different regions of cellular DNA were involved. Thus ASV DNA can be accommodated at many positions in cellular DNA, but the existence of preferred sites has not been excluded. Six of the 15 clones carry only one normal provirus, two contain two normal proviruses, and seven harbor either one or two proviruses that appear anomalous in physical mapping tests. Both ends of at least 18 proviruses, however, were found to contain sequences specific to both the 3' and 5' termini of viral RNA. The organization of these terminally redundant sequences appeared identical to that of the 300 base pair (bp) repeats found at the ends of unintegrated linear DNA (Shank et al., 1978). Proviral DNA is therefore co-extensive, or nearly co-extensive, with unintegrated linear DNA and has a structure we denote as CELL DNA-3'5'----------3'5'-CELL DNA. Three of the four anomalous proviruses which were fully analyzed were deletion mutants lacking 25--65% of the genetic content of ASV; the fourth provirus had a novel site for cleavage by Eco RI but was otherwise normal. Tests for the biological competence of proviral DNA, based upon rescue of transforming virus after fusion with chicken cells, were generally consistent with the physical mapping studies.", "contents": "Proviruses of avian sarcoma virus are terminally redundant, co-extensive with unintegrated linear DNA and integrated at many sites. We have analyzed the DNA from 15 clones of avian sarcoma virus (ASV)-transformed rat cells with restriction endonucleases and molecular hybridization techniques to determine the location and structure of proviral DNA. All twenty units of proviral DNA identified in these 15 clones appear to be inserted at different sites in host DNA. In each of the ten cases that could be sufficiently well mapped, entirely different regions of cellular DNA were involved. Thus ASV DNA can be accommodated at many positions in cellular DNA, but the existence of preferred sites has not been excluded. Six of the 15 clones carry only one normal provirus, two contain two normal proviruses, and seven harbor either one or two proviruses that appear anomalous in physical mapping tests. Both ends of at least 18 proviruses, however, were found to contain sequences specific to both the 3' and 5' termini of viral RNA. The organization of these terminally redundant sequences appeared identical to that of the 300 base pair (bp) repeats found at the ends of unintegrated linear DNA (Shank et al., 1978). Proviral DNA is therefore co-extensive, or nearly co-extensive, with unintegrated linear DNA and has a structure we denote as CELL DNA-3'5'----------3'5'-CELL DNA. Three of the four anomalous proviruses which were fully analyzed were deletion mutants lacking 25--65% of the genetic content of ASV; the fourth provirus had a novel site for cleavage by Eco RI but was otherwise normal. Tests for the biological competence of proviral DNA, based upon rescue of transforming virus after fusion with chicken cells, were generally consistent with the physical mapping studies."}
{"id": "PMID:215326", "title": "Tandem integration of complete and defective SV40 genomes in mouse-human somatic cell hybrids.", "content": "We have analyzed the arrangement of SV40 DNA sequences integrated in human chromosome 7 in two lines of mouse-human somatic cell hybrids: one containing only one human chromosome 7 per cell and the other containing an average of about three. We found that the integration site differs in both the viral and host sequences in the two clones. However, the sites of integration into the several copies of human chromosome 7 of one clone are identical. Each chromosome 7 in both clones carries approximately six viral genomes tandemly linked. Some of these genomes lack about 20% of the DNA from the late region, including the Eco RI site.", "contents": "Tandem integration of complete and defective SV40 genomes in mouse-human somatic cell hybrids. We have analyzed the arrangement of SV40 DNA sequences integrated in human chromosome 7 in two lines of mouse-human somatic cell hybrids: one containing only one human chromosome 7 per cell and the other containing an average of about three. We found that the integration site differs in both the viral and host sequences in the two clones. However, the sites of integration into the several copies of human chromosome 7 of one clone are identical. Each chromosome 7 in both clones carries approximately six viral genomes tandemly linked. Some of these genomes lack about 20% of the DNA from the late region, including the Eco RI site."}
{"id": "PMID:215327", "title": "Three species of polyoma virus tumor antigens share common peptides probably near the amino termini of the proteins.", "content": "Detergent extracts of polyoma virus-infected mouse cells contain three major proteins of approximately 100,000--108,000 (100K), 55,000 (55K) and 21,500 (22K) daltons, which react with sera obtained from rats carrying tumors induced by the virus. A comparison of the 35S-methionine-, 3H-leucine- and 3H-proline-labeled tryptic peptides of each of these proteins by cation-exchange chromatography followed by descending paper chromatography has shown that: at least five peptides are shared by all three T-reactive proteins; at least three peptides are shared by the 55K and 22K proteins, but not by the 100K protein; at least three peptides are found only in the 22K protein; at least six peptides are found only in the 55K protein; and at least sixteen peptides are found only in the 100K protein. The results are consistent with the hypothesis that the polypeptide chains of the 100K, 55K and 22K dalton tumor antigens of polyoma virus share a common virus-coded amino terminal region. The data also suggest that there is a portion of the polypeptide chains (probably immediately adjacent to the common amino terminal region of the molecules) that is shared by the 55K and 22K proteins, but not by the 100K protein (perhaps because this portion of the genetic information is spliced out of the messenger RNA coding for the 100K protein). The facts that all the peptides common to the 100K and 55K proteins are also found in the 22K protein and are thus assigned to the common amino terminal region of the molecules, and that there are several peptides unique to the 100K protein, as well as several peptides unique to the 55K protein, suggest that the presumed carboxy terminal portion of the polypeptide chain of the 100K protein is considerably, if not entirely, different from that of the 55K protein.", "contents": "Three species of polyoma virus tumor antigens share common peptides probably near the amino termini of the proteins. Detergent extracts of polyoma virus-infected mouse cells contain three major proteins of approximately 100,000--108,000 (100K), 55,000 (55K) and 21,500 (22K) daltons, which react with sera obtained from rats carrying tumors induced by the virus. A comparison of the 35S-methionine-, 3H-leucine- and 3H-proline-labeled tryptic peptides of each of these proteins by cation-exchange chromatography followed by descending paper chromatography has shown that: at least five peptides are shared by all three T-reactive proteins; at least three peptides are shared by the 55K and 22K proteins, but not by the 100K protein; at least three peptides are found only in the 22K protein; at least six peptides are found only in the 55K protein; and at least sixteen peptides are found only in the 100K protein. The results are consistent with the hypothesis that the polypeptide chains of the 100K, 55K and 22K dalton tumor antigens of polyoma virus share a common virus-coded amino terminal region. The data also suggest that there is a portion of the polypeptide chains (probably immediately adjacent to the common amino terminal region of the molecules) that is shared by the 55K and 22K proteins, but not by the 100K protein (perhaps because this portion of the genetic information is spliced out of the messenger RNA coding for the 100K protein). The facts that all the peptides common to the 100K and 55K proteins are also found in the 22K protein and are thus assigned to the common amino terminal region of the molecules, and that there are several peptides unique to the 100K protein, as well as several peptides unique to the 55K protein, suggest that the presumed carboxy terminal portion of the polypeptide chain of the 100K protein is considerably, if not entirely, different from that of the 55K protein."}
{"id": "PMID:215328", "title": "An enzymatic activity in uninfected cells that cleaves the linkage between poliovirion RNA and the 5' terminal protein.", "content": "The 5' terminal protein (VPg) on poliovirion RNA can be removed by cell-free extracts from a variety of uninfected cells. This soluble enzymatic activity is found in both nuclear and cytoplasmic extracts of heLa cells and is activated by Mg++. The enzyme activity cleaves the tyrosine-phosphate bond that links the protein to the RNA. In a partially purified form it has insufficient nonspecific protease or nuclease activity to account for its action. The existence of this enzyme implies that poliovirus RNA is translated in cell-free extracts in a form that lacks the 5' terminal protein. The role of this enzyme in the uninfected cell is not known.", "contents": "An enzymatic activity in uninfected cells that cleaves the linkage between poliovirion RNA and the 5' terminal protein. The 5' terminal protein (VPg) on poliovirion RNA can be removed by cell-free extracts from a variety of uninfected cells. This soluble enzymatic activity is found in both nuclear and cytoplasmic extracts of heLa cells and is activated by Mg++. The enzyme activity cleaves the tyrosine-phosphate bond that links the protein to the RNA. In a partially purified form it has insufficient nonspecific protease or nuclease activity to account for its action. The existence of this enzyme implies that poliovirus RNA is translated in cell-free extracts in a form that lacks the 5' terminal protein. The role of this enzyme in the uninfected cell is not known."}
{"id": "PMID:215330", "title": "The matrix (M) protein of vesicular stomatitis virus regulates transcription.", "content": "Temperature-sensitive mutants of vesicular stomatitis virus (VSV) belonging to complementation group III contain a lesion in the matrix (M) protein. This results in a 2--5 fold increase in transcription at the nonpermissive temperature. Co-infection of cells with one of these mutants and wild-type virus reverses this mutant phenotype. Separation of the transcriptional and translational products from mutant-infected cells reveals an overall increase in each of the viral mRNA species concomitant with degradation of the M protein at the nonpermissive temperature. The increase in mRNA, however, does not lead to increased synthesis of viral proteins. Quantitation of individual mRNA species indicates that M protein acts as a direct inhibitor of transcription as well as an attenuator of sequential transcription.", "contents": "The matrix (M) protein of vesicular stomatitis virus regulates transcription. Temperature-sensitive mutants of vesicular stomatitis virus (VSV) belonging to complementation group III contain a lesion in the matrix (M) protein. This results in a 2--5 fold increase in transcription at the nonpermissive temperature. Co-infection of cells with one of these mutants and wild-type virus reverses this mutant phenotype. Separation of the transcriptional and translational products from mutant-infected cells reveals an overall increase in each of the viral mRNA species concomitant with degradation of the M protein at the nonpermissive temperature. The increase in mRNA, however, does not lead to increased synthesis of viral proteins. Quantitation of individual mRNA species indicates that M protein acts as a direct inhibitor of transcription as well as an attenuator of sequential transcription."}
{"id": "PMID:215337", "title": "The International Reference Preparations of Clostridium welchii (C. perfringens) beta and epsilon toxoids.", "content": "The Central Veterinary Laboratory, Weybridge, England was requested by the WHO Expert Committee on Biological Standardization to obtain suitable materials for international standards for Clostridium welchii (C. perfringens) beta and epsilon toxoids and to arrange collaborative assays. Preparations were obtained and dispensed as freeze-dried toxoids in ampoules. The toxoids were assayed by nine laboratories in eight countries. On the basis of the results obtained, the materials have been established as the International Reference Preparations of Clostridium welchii (C. perfringens) Beta and Epsilon Toxoids.", "contents": "The International Reference Preparations of Clostridium welchii (C. perfringens) beta and epsilon toxoids. The Central Veterinary Laboratory, Weybridge, England was requested by the WHO Expert Committee on Biological Standardization to obtain suitable materials for international standards for Clostridium welchii (C. perfringens) beta and epsilon toxoids and to arrange collaborative assays. Preparations were obtained and dispensed as freeze-dried toxoids in ampoules. The toxoids were assayed by nine laboratories in eight countries. On the basis of the results obtained, the materials have been established as the International Reference Preparations of Clostridium welchii (C. perfringens) Beta and Epsilon Toxoids."}
{"id": "PMID:215338", "title": "Use of combined diet and colestipol in long-term (7--7 1/2 years) treatment of patients with type II hyperlipoproteinemia.", "content": "Long-term effects of diet and colestipol (a bile acid sequestrant) were studied in 25 patients with familial type II hyperlipoproteinemia. Serum lipids and body weights of an initial group of 30 patients were stabilized by low cholesterol-saturated fat-refined carbohydrate diet and the patients were then randomized into placebo and drug-treatment groups. After explaining that the drug is nontoxic and effective in lowering serum lipids, total cholesterol (C) and low-density lipoprotein cholesterol (LDL-C), colestipol (30 g/day) and diet were given to the 25 patients who remained in the long-term follow-up program. The treatment resulted in highly significant lowering of serum lipids (mg/dl, mean +/- SEM): C and LDL-C from 412.7 +/- 24.4 and 331.1 +/- 22.8 to 270 +/- 11.0 and 188.1 +/- 13.8, respectively (p less than 0.001 in each instance) over 7--7 1/2 years. Although we observed no absolute increase in high density lipoprotein (HDL), the HDL/LDL ratio was elevated. Long-term colestipol and diet treatment reduced the xanthoma size and stabilized serially angiographically visualized atherosclerotic lesions in 21 of the 25 patients who showed a satisfactory hypolipemic response. It did not cause nutritional or metabolic disturbances.", "contents": "Use of combined diet and colestipol in long-term (7--7 1/2 years) treatment of patients with type II hyperlipoproteinemia. Long-term effects of diet and colestipol (a bile acid sequestrant) were studied in 25 patients with familial type II hyperlipoproteinemia. Serum lipids and body weights of an initial group of 30 patients were stabilized by low cholesterol-saturated fat-refined carbohydrate diet and the patients were then randomized into placebo and drug-treatment groups. After explaining that the drug is nontoxic and effective in lowering serum lipids, total cholesterol (C) and low-density lipoprotein cholesterol (LDL-C), colestipol (30 g/day) and diet were given to the 25 patients who remained in the long-term follow-up program. The treatment resulted in highly significant lowering of serum lipids (mg/dl, mean +/- SEM): C and LDL-C from 412.7 +/- 24.4 and 331.1 +/- 22.8 to 270 +/- 11.0 and 188.1 +/- 13.8, respectively (p less than 0.001 in each instance) over 7--7 1/2 years. Although we observed no absolute increase in high density lipoprotein (HDL), the HDL/LDL ratio was elevated. Long-term colestipol and diet treatment reduced the xanthoma size and stabilized serially angiographically visualized atherosclerotic lesions in 21 of the 25 patients who showed a satisfactory hypolipemic response. It did not cause nutritional or metabolic disturbances."}
{"id": "PMID:215339", "title": "Effect of beta-adrenergic suppression by propranolol on coronary collateral development in response to chronic coronary ischemia in dogs.", "content": "Acute left circumflex coronary artery (LC) occlusion in conscious dogs caused marked ischemia in the myocardium supplied by the occluded artery, as judged by the radioactive microsphere technique for determining blood flow distribution. With the chest open, LC pressure distal to the occlusion fell to 21 +/- 1.9% of aortic pressure. By 8 weeks after gradual LC occlusion with an ameroid constrictor, collateral development had restored coronary blood flow distribution to near-normal under basal conditions and during pacing, at a heart rate of 200 beats/min. The only evidence for ischemia was in the subepicardium within the distribution of the unoccluded left anterior descending artery, which provided the extra collateral blood flow. Distal LC pressure was 70 +/- 1.7% of aortic pressure. Propranolol 160 mg orally every 6 hours for 8 weeks had no detectable effect on coronary collateral development, as judged by blood flow distribution or distal LC pressure. The only significant difference for the propranolol dogs was a slight transmural shift away from the subendocardium in the left anterior descending region.", "contents": "Effect of beta-adrenergic suppression by propranolol on coronary collateral development in response to chronic coronary ischemia in dogs. Acute left circumflex coronary artery (LC) occlusion in conscious dogs caused marked ischemia in the myocardium supplied by the occluded artery, as judged by the radioactive microsphere technique for determining blood flow distribution. With the chest open, LC pressure distal to the occlusion fell to 21 +/- 1.9% of aortic pressure. By 8 weeks after gradual LC occlusion with an ameroid constrictor, collateral development had restored coronary blood flow distribution to near-normal under basal conditions and during pacing, at a heart rate of 200 beats/min. The only evidence for ischemia was in the subepicardium within the distribution of the unoccluded left anterior descending artery, which provided the extra collateral blood flow. Distal LC pressure was 70 +/- 1.7% of aortic pressure. Propranolol 160 mg orally every 6 hours for 8 weeks had no detectable effect on coronary collateral development, as judged by blood flow distribution or distal LC pressure. The only significant difference for the propranolol dogs was a slight transmural shift away from the subendocardium in the left anterior descending region."}
{"id": "PMID:215340", "title": "Ventricular aneurysms complicating coxsackievirus group B, types 1 and 4 murine myocarditis.", "content": "Suckling Swiss Webster mice were inoculated with 10(4)TCD50 of coxsackieviruses, group B types 1 or 4. Virulent necrotizing myocarditis resulted in 185 infected mice. Of the latter group, three (14.3%) nurslings on the 17th and 23rd day after inoculations had left ventricular aneurysms postmortem. None of 61 concurrently matched control mice developed aneurysms. Ventricular aneurysm is a suggested but previously undocumented complication of murine, and possibly human necrotizing transmural coxsackievirus myocarditis.", "contents": "Ventricular aneurysms complicating coxsackievirus group B, types 1 and 4 murine myocarditis. Suckling Swiss Webster mice were inoculated with 10(4)TCD50 of coxsackieviruses, group B types 1 or 4. Virulent necrotizing myocarditis resulted in 185 infected mice. Of the latter group, three (14.3%) nurslings on the 17th and 23rd day after inoculations had left ventricular aneurysms postmortem. None of 61 concurrently matched control mice developed aneurysms. Ventricular aneurysm is a suggested but previously undocumented complication of murine, and possibly human necrotizing transmural coxsackievirus myocarditis."}
{"id": "PMID:215341", "title": "New saccharogenic determination of alpha-amylase in serum and urine.", "content": "I describe a new kinetic enzymatic saccharogenic method for assaying alpha-amylase in human serum and urine. alpha-Amylase liberates maltose from starch. This is successively acted on by alpha-glucosidase, mutarotase, and glucose dehydrogenase. The resulting conversion of NAD+ to NADH, measured at 340 nm, during a 20-min incubation reflects amylase activity. Endogenous glucose is destroyed before measurement of amylase activity is begun.", "contents": "New saccharogenic determination of alpha-amylase in serum and urine. I describe a new kinetic enzymatic saccharogenic method for assaying alpha-amylase in human serum and urine. alpha-Amylase liberates maltose from starch. This is successively acted on by alpha-glucosidase, mutarotase, and glucose dehydrogenase. The resulting conversion of NAD+ to NADH, measured at 340 nm, during a 20-min incubation reflects amylase activity. Endogenous glucose is destroyed before measurement of amylase activity is begun."}
{"id": "PMID:215342", "title": "Nephelometry of apolipoprotein B in human serum.", "content": "We studied the development of light scattering in the reaction between anti-apolipoprotein B and apolipoprotein B in intact very-low-density lipoproteins (I) and low-density lipoproteins (II) as well as in lipoproteins treated with lipases, and found considerable differences in the kinetics of the immunoreaction for the two lipoprotein classes. Pre-incubation with triglyceride lipase and cholesterol esterase caused a decrease of final light scattering in I but only minimal changes in the reaction with II. Non-ionic detergent not only decreased the original light scattering in hyperlipemic serum samples, but also accelerated the immunoreaction. Under standardized conditions, results of quantitative nephelometry correlated highly significantly with quantitative determination of apolipoprotein B by radial immunodiffusion, both for normolipemic and hyperlipoproteinemic serum samples. The nonspecific light scattering caused by neutral lipids in intact lipoproteins could be minimized when samples were pre-incubated with lipolytic enzymes.", "contents": "Nephelometry of apolipoprotein B in human serum. We studied the development of light scattering in the reaction between anti-apolipoprotein B and apolipoprotein B in intact very-low-density lipoproteins (I) and low-density lipoproteins (II) as well as in lipoproteins treated with lipases, and found considerable differences in the kinetics of the immunoreaction for the two lipoprotein classes. Pre-incubation with triglyceride lipase and cholesterol esterase caused a decrease of final light scattering in I but only minimal changes in the reaction with II. Non-ionic detergent not only decreased the original light scattering in hyperlipemic serum samples, but also accelerated the immunoreaction. Under standardized conditions, results of quantitative nephelometry correlated highly significantly with quantitative determination of apolipoprotein B by radial immunodiffusion, both for normolipemic and hyperlipoproteinemic serum samples. The nonspecific light scattering caused by neutral lipids in intact lipoproteins could be minimized when samples were pre-incubated with lipolytic enzymes."}
{"id": "PMID:215343", "title": "Rapid fluorometry of estrogens in nonpregnancy urine, with use of chloroform extraction and purification by anion-exchange chromatography.", "content": "We describe a new method of extraction and purification of estrogens in low concentration in urine, involving a rapid enzymic hydrolysis of a 10-mL sample, automatic extraction (in a tube) with CHCl3/ethyl acetate, purification by chromatography on a disposable \"mini-column\" of AG 1-X2, and fluorometry by continuous flow according to Itrich's procedure [Acta Endocrinol. (Copenhagen) 35, 34 (1960)]. Conditions of hydrolysis, extraction, and purification were studied. Within-day precision (CV) was 7.5%, the mean between-day precision 8.5%. The sensitivity was 6 microgram of total estrogens per liter of urine. The specificity was assessed particularly by comparison with the results obtained by Sch\u00f6ller et al. [Acta Endocrinol. (Copenhagen) 57, suppl. 107 (1966)] and by gas-chromatography-mass-spectrometry. The normal limits as calculated by this technique were identical to values reported by others. The technique is rapid; results are obtained in 3 h. It is quite suitable for routine determinations: 100 assays can be done by a team of three technicians in one working day.", "contents": "Rapid fluorometry of estrogens in nonpregnancy urine, with use of chloroform extraction and purification by anion-exchange chromatography. We describe a new method of extraction and purification of estrogens in low concentration in urine, involving a rapid enzymic hydrolysis of a 10-mL sample, automatic extraction (in a tube) with CHCl3/ethyl acetate, purification by chromatography on a disposable \"mini-column\" of AG 1-X2, and fluorometry by continuous flow according to Itrich's procedure [Acta Endocrinol. (Copenhagen) 35, 34 (1960)]. Conditions of hydrolysis, extraction, and purification were studied. Within-day precision (CV) was 7.5%, the mean between-day precision 8.5%. The sensitivity was 6 microgram of total estrogens per liter of urine. The specificity was assessed particularly by comparison with the results obtained by Sch\u00f6ller et al. [Acta Endocrinol. (Copenhagen) 57, suppl. 107 (1966)] and by gas-chromatography-mass-spectrometry. The normal limits as calculated by this technique were identical to values reported by others. The technique is rapid; results are obtained in 3 h. It is quite suitable for routine determinations: 100 assays can be done by a team of three technicians in one working day."}
{"id": "PMID:215344", "title": "Reversed-phase liquid chromatographic separation of 3',5'-cyclic ribonucleotides.", "content": "A rapid, reversed-phase \"high-performance\" liquid-chromatographic separation of the five naturally occurring cyclic ribonucleotides is described. The separation, optimized for the measurement of these compounds in biological samples, is short (25 min), sensitive (50-100 pmol), and requires no sample pre-concentration steps. We also report an alternative isocratic elution mode, optimized for a rapid and selective analysis for adenosine 3',5'-cyclic phosphate. The identity of chromatographic peaks in biological extracts is confirmed by several methods: retention times, co-chromatography with the reference compounds, absorbance ratios, enzymatic peak-shift with cyclic nucleotide phosphodiesterase, and stopped-flow ultraviolet-scanning techniques.", "contents": "Reversed-phase liquid chromatographic separation of 3',5'-cyclic ribonucleotides. A rapid, reversed-phase \"high-performance\" liquid-chromatographic separation of the five naturally occurring cyclic ribonucleotides is described. The separation, optimized for the measurement of these compounds in biological samples, is short (25 min), sensitive (50-100 pmol), and requires no sample pre-concentration steps. We also report an alternative isocratic elution mode, optimized for a rapid and selective analysis for adenosine 3',5'-cyclic phosphate. The identity of chromatographic peaks in biological extracts is confirmed by several methods: retention times, co-chromatography with the reference compounds, absorbance ratios, enzymatic peak-shift with cyclic nucleotide phosphodiesterase, and stopped-flow ultraviolet-scanning techniques."}
{"id": "PMID:215345", "title": "Efficacy of a simplified primary screening procedure for detection of hyperlipoproteinemias in a pediatric population.", "content": "We examined the efficacy of a simple primary screening procedure for detecting beta- and pre-beta-lipoprotein abnormalities in 3183 children, ages 5-14, residing in Bogalusa, Louisiana. This procedure is based on the ability of beta- and pre-beta-lipoproteins to form insoluble complexes with heparin in the presence of Ca2+; the turbidity produced by the reaction was considered as an index of the concentration of these two classes of lipoproteins. Our results indicate a close relationship (r = 0.88) between the beta- + pre-beta-lipoprotein index (turbidity) and the concentrations of these lipoproteins. Comparison of serum lipid and beta- + pre-beta-lipoprotein values of 5% of the children whose results fell outside the normal limits (upper and lower 5%) indicated that serum total cholesterol was not reflecting the beta- + pre-beta-lipoprotein concentration of a given child. The variability of alpha-lipoprotein concentration in these children accounted for this discrepancy. Measuring the serum beta- + pre-beta-lipoprotein index may be more useful for large-scale screening and for detecting subtle abnormalities than are determinations of either cholesterol or triglycerides.", "contents": "Efficacy of a simplified primary screening procedure for detection of hyperlipoproteinemias in a pediatric population. We examined the efficacy of a simple primary screening procedure for detecting beta- and pre-beta-lipoprotein abnormalities in 3183 children, ages 5-14, residing in Bogalusa, Louisiana. This procedure is based on the ability of beta- and pre-beta-lipoproteins to form insoluble complexes with heparin in the presence of Ca2+; the turbidity produced by the reaction was considered as an index of the concentration of these two classes of lipoproteins. Our results indicate a close relationship (r = 0.88) between the beta- + pre-beta-lipoprotein index (turbidity) and the concentrations of these lipoproteins. Comparison of serum lipid and beta- + pre-beta-lipoprotein values of 5% of the children whose results fell outside the normal limits (upper and lower 5%) indicated that serum total cholesterol was not reflecting the beta- + pre-beta-lipoprotein concentration of a given child. The variability of alpha-lipoprotein concentration in these children accounted for this discrepancy. Measuring the serum beta- + pre-beta-lipoprotein index may be more useful for large-scale screening and for detecting subtle abnormalities than are determinations of either cholesterol or triglycerides."}
{"id": "PMID:215346", "title": "Re-evaluation of turbidimetry of proteins by use of aromatic sulfonic acids and chloroacetic acids.", "content": "From studies on 11 different proteins (including native albumin and albumin with reduced disulfide-bridges) treated with sulfosalicylic, 2-naphthalenesulfonic, toluenesulfonic, dichloroacetic, or trichloroacetic acids, we elucidate the interactions determining the resulting turbidities and other factors affecting turbidities, and we discuss the clinical utility of such turbidimetry. At least three interactions are important in determining turbidity: reduction of positive charges on the protein, hydrogen bonding of the non-ionized chloroacetic acids with the protein, and hydrophobic interaction of the aromatic sulfonic acids with albumin. Turbidity varies appreciably with the species of acid and protein, concentrations of acid, temperature, and standing time after acid is added. We conclude that this technique should be restricted to confirming proteinuria.", "contents": "Re-evaluation of turbidimetry of proteins by use of aromatic sulfonic acids and chloroacetic acids. From studies on 11 different proteins (including native albumin and albumin with reduced disulfide-bridges) treated with sulfosalicylic, 2-naphthalenesulfonic, toluenesulfonic, dichloroacetic, or trichloroacetic acids, we elucidate the interactions determining the resulting turbidities and other factors affecting turbidities, and we discuss the clinical utility of such turbidimetry. At least three interactions are important in determining turbidity: reduction of positive charges on the protein, hydrogen bonding of the non-ionized chloroacetic acids with the protein, and hydrophobic interaction of the aromatic sulfonic acids with albumin. Turbidity varies appreciably with the species of acid and protein, concentrations of acid, temperature, and standing time after acid is added. We conclude that this technique should be restricted to confirming proteinuria."}
{"id": "PMID:215347", "title": "Lactate-to-pyruvate or pyruvate-to-lactate assay for lactate dehydrogenase: a re-examination.", "content": "The pyruvate-to-lactate assay for determining lactate dehydrogenase (EC 1.1.1.27) can now yield linearity equal to or better than that obtained by the lactate-to-pyruvate assay. In addition, there are significant advantages to the pyruvate-to-lactate reaction: (a) a greater change in absorbance per unit time, which allows more accurate spectrophotometric readout; (b) lower reactant concentrations are required, which substantially reduces the cost per assay; (c) solid reagents are used to prepare the assay solution; and (d) reagent solutions are more stable. However, impurities present in commercial NADH preparations may substantially affect measured lactated dehydrogenase activities; therefore, a Standard Reference Material for NADH is being developed for issuance by the National Bureau of Standards.", "contents": "Lactate-to-pyruvate or pyruvate-to-lactate assay for lactate dehydrogenase: a re-examination. The pyruvate-to-lactate assay for determining lactate dehydrogenase (EC 1.1.1.27) can now yield linearity equal to or better than that obtained by the lactate-to-pyruvate assay. In addition, there are significant advantages to the pyruvate-to-lactate reaction: (a) a greater change in absorbance per unit time, which allows more accurate spectrophotometric readout; (b) lower reactant concentrations are required, which substantially reduces the cost per assay; (c) solid reagents are used to prepare the assay solution; and (d) reagent solutions are more stable. However, impurities present in commercial NADH preparations may substantially affect measured lactated dehydrogenase activities; therefore, a Standard Reference Material for NADH is being developed for issuance by the National Bureau of Standards."}
{"id": "PMID:215348", "title": "Gel isoelectric focusing method for specific diagnosis of familial hyperlipoproteinemia type 3.", "content": "We describe a gel isoelectric focusing procedure for resolving into at least five bands the arginine-rich protein of very-low-density lipoproteins, and use the method in diagnosis of hyperlipoproteinemia type 3. We find that deficiency of one band, designated E3, relative to E2, expressed as an E3/E2 ratio less than or equal to 0.3, is specifically associated with hyperlipoproteinemia type 3 as diagnosed by traditional criteria in a large family study. In addition, we used the procedure to test 47 referral samples with demonstrable beta-migrating very-low-density liproprotein grouped by very-low-density lipoprotein cholesterol/total triglyceride ratios of greater than or equal to 0.3, from 0.25 to 0.3, and less than 0.25. All 24 of the first group, three of six in the second, and only one of 17 in the third had E3/E2 ratios of less than or equal to 0.3. Also, two normolipidemic children, without detectable lipoprotein abnormalities but related to subjects with hyperlipoproteinemia type 3, had E3/E2 ratios of less than or equal to 0.3. Use of our procedure improves the specificity of diagnosis and allows sensitive detection of asymptomatic subjects who may be at risk of developing the disorder.", "contents": "Gel isoelectric focusing method for specific diagnosis of familial hyperlipoproteinemia type 3. We describe a gel isoelectric focusing procedure for resolving into at least five bands the arginine-rich protein of very-low-density lipoproteins, and use the method in diagnosis of hyperlipoproteinemia type 3. We find that deficiency of one band, designated E3, relative to E2, expressed as an E3/E2 ratio less than or equal to 0.3, is specifically associated with hyperlipoproteinemia type 3 as diagnosed by traditional criteria in a large family study. In addition, we used the procedure to test 47 referral samples with demonstrable beta-migrating very-low-density liproprotein grouped by very-low-density lipoprotein cholesterol/total triglyceride ratios of greater than or equal to 0.3, from 0.25 to 0.3, and less than 0.25. All 24 of the first group, three of six in the second, and only one of 17 in the third had E3/E2 ratios of less than or equal to 0.3. Also, two normolipidemic children, without detectable lipoprotein abnormalities but related to subjects with hyperlipoproteinemia type 3, had E3/E2 ratios of less than or equal to 0.3. Use of our procedure improves the specificity of diagnosis and allows sensitive detection of asymptomatic subjects who may be at risk of developing the disorder."}
{"id": "PMID:215349", "title": "An enzymic and centrifugal method for estimating high-density lipoprotein cholesterol.", "content": "Enzymic measurement of high-density lipoprotein cholesterol with a centrifugal analyzer is described. We used polyethylene glycol (Mr 6000), final concentration 100 g/L, to precipitate low-density and very-low-density lipoproteins, thereby eliminating the difficulties of the commonly used heparin/Mn2+ precipitation method and facilitating the use of ethylenediaminetetraacetate-stabilized plasma. As measured by rocket immunoelectrophoresis, this final concentration of polyethylene glycol completely precipitates beta-lipoproteins, leaving the alpha-lipoproteins in solution. Between-run reproducibility (CV) was 3.6%, within-run reproducibility (CV) 0.8%. Reagent costs currently are $US 0.13 per test and large numbers of samples can be handled conveniently. Normal ranges were compiled for 539 men and 444 women. The high-density lipoprotein cholesterol for men was 1.20 +/- 0.31 (SD) mmol/L and for women 1.52 +/- 0.38 (SD) mmol/L.", "contents": "An enzymic and centrifugal method for estimating high-density lipoprotein cholesterol. Enzymic measurement of high-density lipoprotein cholesterol with a centrifugal analyzer is described. We used polyethylene glycol (Mr 6000), final concentration 100 g/L, to precipitate low-density and very-low-density lipoproteins, thereby eliminating the difficulties of the commonly used heparin/Mn2+ precipitation method and facilitating the use of ethylenediaminetetraacetate-stabilized plasma. As measured by rocket immunoelectrophoresis, this final concentration of polyethylene glycol completely precipitates beta-lipoproteins, leaving the alpha-lipoproteins in solution. Between-run reproducibility (CV) was 3.6%, within-run reproducibility (CV) 0.8%. Reagent costs currently are $US 0.13 per test and large numbers of samples can be handled conveniently. Normal ranges were compiled for 539 men and 444 women. The high-density lipoprotein cholesterol for men was 1.20 +/- 0.31 (SD) mmol/L and for women 1.52 +/- 0.38 (SD) mmol/L."}
{"id": "PMID:215350", "title": "A radiochemical method for the determination of transketolase activity in erythrocyte hemolysates.", "content": "A radiochemical method for the determination of transketolase activity is reported. It is based on incubation of erythrocyte hemolysates with radioactive ribose 5-phosphate followed by isolation of sedoheptulose 7-phosphate on anion-exchange columns. The experimental conditions are discussed and the presence of phosphatase activity in the incubation mixture is demonstrated. The proposed method is compared with a current colorimetric method. Reference values are given for the transketolase activity and the thiamine pyrophosphate effect.", "contents": "A radiochemical method for the determination of transketolase activity in erythrocyte hemolysates. A radiochemical method for the determination of transketolase activity is reported. It is based on incubation of erythrocyte hemolysates with radioactive ribose 5-phosphate followed by isolation of sedoheptulose 7-phosphate on anion-exchange columns. The experimental conditions are discussed and the presence of phosphatase activity in the incubation mixture is demonstrated. The proposed method is compared with a current colorimetric method. Reference values are given for the transketolase activity and the thiamine pyrophosphate effect."}
{"id": "PMID:215351", "title": "Concentration and composition of human serum lipoproteins at birth.", "content": "By ultracentrifugation of sera from 69 cord bloods very low (VLDL), low (LDL) and high density lipoproteins (HDL) were obtained and analysed for triglycerides (TG) and cholesterol (CHOL). Electrophoresis in agarose gel was performed on serum, VLDL and LDL + HDL. VLDL lipids were present in all newborns. VLDL contained 30 and 5% of serum TG and CHOL. The range of TG in VLDL was wide (0.02-0.62 mmol/l), but there was a constant ratio between TG and CHOL. The electrophoretic mobility of VLDL was slower than in adults. LDL contained 50% of both serum TG and CHOL, and HDL contained 15 and 50% of these serum lipids. A published formula for calculating CHOL in VLDL and LDL from serum CHOL and TG and CHOL in HDL gave values for CHOL in LDL which corresponded well with the determined values. For VLDL, however, the calculated values were too high.", "contents": "Concentration and composition of human serum lipoproteins at birth. By ultracentrifugation of sera from 69 cord bloods very low (VLDL), low (LDL) and high density lipoproteins (HDL) were obtained and analysed for triglycerides (TG) and cholesterol (CHOL). Electrophoresis in agarose gel was performed on serum, VLDL and LDL + HDL. VLDL lipids were present in all newborns. VLDL contained 30 and 5% of serum TG and CHOL. The range of TG in VLDL was wide (0.02-0.62 mmol/l), but there was a constant ratio between TG and CHOL. The electrophoretic mobility of VLDL was slower than in adults. LDL contained 50% of both serum TG and CHOL, and HDL contained 15 and 50% of these serum lipids. A published formula for calculating CHOL in VLDL and LDL from serum CHOL and TG and CHOL in HDL gave values for CHOL in LDL which corresponded well with the determined values. For VLDL, however, the calculated values were too high."}
{"id": "PMID:215353", "title": "[Lipoprotein electrophoresis on acrylamide-agarose plates, with discontinuous acrylamide gradient].", "content": "We describe a modified lipoprotein electrophoresis on acrylamide gel. The lipoproteins, prestained with Sudan Black, are separated by running on acrylamide-agarose gels, with two different concentrations of acrylamide and a constant concentration of agarose. The sera are deposited in the first gel (2% acrylamide). Chylomicrons remain at origin and other lipoproteins run through the first gel to the second one (3% acrylamide gel). VLDL stays at the junction of both gels, LDL and HDL are separated in the 3% acrylamide gel. By this technique, we were able to detect an increase of Lp(a) and to identify the different types of hyperlipoproteinemia. After running, the plates can be treated for storage.", "contents": "[Lipoprotein electrophoresis on acrylamide-agarose plates, with discontinuous acrylamide gradient]. We describe a modified lipoprotein electrophoresis on acrylamide gel. The lipoproteins, prestained with Sudan Black, are separated by running on acrylamide-agarose gels, with two different concentrations of acrylamide and a constant concentration of agarose. The sera are deposited in the first gel (2% acrylamide). Chylomicrons remain at origin and other lipoproteins run through the first gel to the second one (3% acrylamide gel). VLDL stays at the junction of both gels, LDL and HDL are separated in the 3% acrylamide gel. By this technique, we were able to detect an increase of Lp(a) and to identify the different types of hyperlipoproteinemia. After running, the plates can be treated for storage."}
{"id": "PMID:215357", "title": "Hormonal control of oocyte meiosis, ovulation and luteinization in mammals.", "content": "The ovulatory process can be regarded as a series of biochemical and morphological changes ultimately leading to the release of a mature oocyte and the transformation of the Graafian follicle into the corpus luteum. This process involves acute changes in steroidogenesis, resumption of oocyte meiosis, and finally rupture of the follicular wall and luteinization of the granulosa cells. Normally, all of these changes are induced synchronously by the pre-ovulatory LH surge. Experimentally, however, these changes in steroidogenesis, oocyte maturation and follicular rupture can be dissociated from each other showing that the LH effect is mediated via different cellular messengers. The gonadotrophins act in an orderly sequence to induce follicular maturation. The granulosa cells increase their number of LH receptors and respond to LH with increased stimulation of cyclic AMP accumulation and progesterone secretion. Concomitantly, they decrease in their FSH receptors and their response to FSH diminishes in terms of ability to stimulate cyclic AMP accumulation. The ovulatory process is associated with increased uptake of LH by the follicle; when granulosa cells are obtained from pre-ovulatory follicles and cultured they luteinize spontaneously. Steroid hormones modulate the actions of gonadotrophins on follicular maturation. In addition, there are non-steroidal factors in follicular fluid which regulate follicular maturation: an oocyte maturation inhibitor keeps the oocyte in meiotic arrest; a luteinizing inhibitor prevents the granulosa cells from luteinizing prior to follicular rupture; a folliculostatin inhibits FSH release from the pituitary gland. The functional activity and the lifespan of the corpus luteum depend on adequate pre-ovulatory as well as post-ovulatory gonadotrophic stimulation. Its lifespan may also be regulated by an LH binding inhibitor.", "contents": "Hormonal control of oocyte meiosis, ovulation and luteinization in mammals. The ovulatory process can be regarded as a series of biochemical and morphological changes ultimately leading to the release of a mature oocyte and the transformation of the Graafian follicle into the corpus luteum. This process involves acute changes in steroidogenesis, resumption of oocyte meiosis, and finally rupture of the follicular wall and luteinization of the granulosa cells. Normally, all of these changes are induced synchronously by the pre-ovulatory LH surge. Experimentally, however, these changes in steroidogenesis, oocyte maturation and follicular rupture can be dissociated from each other showing that the LH effect is mediated via different cellular messengers. The gonadotrophins act in an orderly sequence to induce follicular maturation. The granulosa cells increase their number of LH receptors and respond to LH with increased stimulation of cyclic AMP accumulation and progesterone secretion. Concomitantly, they decrease in their FSH receptors and their response to FSH diminishes in terms of ability to stimulate cyclic AMP accumulation. The ovulatory process is associated with increased uptake of LH by the follicle; when granulosa cells are obtained from pre-ovulatory follicles and cultured they luteinize spontaneously. Steroid hormones modulate the actions of gonadotrophins on follicular maturation. In addition, there are non-steroidal factors in follicular fluid which regulate follicular maturation: an oocyte maturation inhibitor keeps the oocyte in meiotic arrest; a luteinizing inhibitor prevents the granulosa cells from luteinizing prior to follicular rupture; a folliculostatin inhibits FSH release from the pituitary gland. The functional activity and the lifespan of the corpus luteum depend on adequate pre-ovulatory as well as post-ovulatory gonadotrophic stimulation. Its lifespan may also be regulated by an LH binding inhibitor."}
{"id": "PMID:215358", "title": "Polymorphism of apolipoprotein E. I. Methodological aspects and diagnosis of hyperlipoproteinemia type III without ultracentrifugation.", "content": "Two methods for phenotyping apolipoprotein E are compared. One is based on preparation of VLDL by conventional ultracentrifugation, whereas the other uses heparin/Mg precipitation of VLDG. In principle, the same results were obtained by both methods. However, the group limits for the three different phenotypes Apo E-N, Apo E-ND and Apo E-D were slightly different by the two methods. Phenotype Apo E-D - the phenotype characterizing type III dyslipoproteinemia - is clearly definable by both methods. Hence the precipitation-I.E.F. method for Apo E phenotyping provides a simple tool for genetic and population genetic studies and also for the routine diagnosis of hyperlipoproteinemia type III, based on the only specific marker known for this disease.", "contents": "Polymorphism of apolipoprotein E. I. Methodological aspects and diagnosis of hyperlipoproteinemia type III without ultracentrifugation. Two methods for phenotyping apolipoprotein E are compared. One is based on preparation of VLDL by conventional ultracentrifugation, whereas the other uses heparin/Mg precipitation of VLDG. In principle, the same results were obtained by both methods. However, the group limits for the three different phenotypes Apo E-N, Apo E-ND and Apo E-D were slightly different by the two methods. Phenotype Apo E-D - the phenotype characterizing type III dyslipoproteinemia - is clearly definable by both methods. Hence the precipitation-I.E.F. method for Apo E phenotyping provides a simple tool for genetic and population genetic studies and also for the routine diagnosis of hyperlipoproteinemia type III, based on the only specific marker known for this disease."}
{"id": "PMID:215359", "title": "Use of microtechniques for the detection of lysosomal enzyme disorders: Tay-Sachs disease, Gm1-gangliosidosis and Fabry disease.", "content": "A preliminary report on the use of microtechniques for the detection of three lysosomal storage diseases (Tay-Sachs, GM1-gangliosidosis and Fabry disease) is presented. This microassay method uses from 100 to 300 cultured amniotic fluid cells or skin fibroblasts. A comparison between values for total activity and heat inactivated forms of hexosaminidase (in Tay-Sachs disease) is presented. The feasibility of the use of this microtechnique in prenatal diagnosis is discussed.", "contents": "Use of microtechniques for the detection of lysosomal enzyme disorders: Tay-Sachs disease, Gm1-gangliosidosis and Fabry disease. A preliminary report on the use of microtechniques for the detection of three lysosomal storage diseases (Tay-Sachs, GM1-gangliosidosis and Fabry disease) is presented. This microassay method uses from 100 to 300 cultured amniotic fluid cells or skin fibroblasts. A comparison between values for total activity and heat inactivated forms of hexosaminidase (in Tay-Sachs disease) is presented. The feasibility of the use of this microtechnique in prenatal diagnosis is discussed."}
{"id": "PMID:215360", "title": "Polymorphism of apolipoprotein E. II. Genetics of hyperlipoproteinemia type III.", "content": "Apolipoprotein E from human serum shows a genetic polymorphism determined by two autosomal codominant alleles, Apo En and Apo Ed. Homozygosity for the gene Apo Ed (phenotype Apo E-D) results in primary dysbetalipoproteinemia, but only some individuals with this phenotype develop gross hyperlipidemia (hyperlipoproteinemia type III). Vertical transmission of dysbetalipoproteinemia represents pseudodominance due to the high frequency of the gene Apo Ed. Dysbetalipoproteinemia is already expressed in childhood. To assess the influence of other genes on the expression of hyperlipidemia in phenotype Apo E-D, comparative studies were carried out in kindreds of hypercholesterolemic (group A) and normo- or hypocholesterolemic probands with dysbetalipoproteinemia (group B). This demonstrated the occurrence of familial (non-type III) forms of hyperlipidemia in group A but not in group B kindreds. Distribution of lipoprotein phenotypes in five of the group A kindreds was consistent with the occurrence of familial combined hyperlipidemia. Apo E phenotypes and hyperlipidemia segregated independently. It is concluded that primary dysbetalipoproteinemia is a frequent monogenic variant of lipoprotein metabolism, but not a disease. Coincidence in one individual of genes for this specific dyslipoproteinemia with any of the genes for monogenic or polygenic forms of familial hyperlipidemia results in hyperlipoproteinemia type III. Hence hyperlipoproteinemia type III is caused by at least two non-allelic genes and is a polygenic disorder.", "contents": "Polymorphism of apolipoprotein E. II. Genetics of hyperlipoproteinemia type III. Apolipoprotein E from human serum shows a genetic polymorphism determined by two autosomal codominant alleles, Apo En and Apo Ed. Homozygosity for the gene Apo Ed (phenotype Apo E-D) results in primary dysbetalipoproteinemia, but only some individuals with this phenotype develop gross hyperlipidemia (hyperlipoproteinemia type III). Vertical transmission of dysbetalipoproteinemia represents pseudodominance due to the high frequency of the gene Apo Ed. Dysbetalipoproteinemia is already expressed in childhood. To assess the influence of other genes on the expression of hyperlipidemia in phenotype Apo E-D, comparative studies were carried out in kindreds of hypercholesterolemic (group A) and normo- or hypocholesterolemic probands with dysbetalipoproteinemia (group B). This demonstrated the occurrence of familial (non-type III) forms of hyperlipidemia in group A but not in group B kindreds. Distribution of lipoprotein phenotypes in five of the group A kindreds was consistent with the occurrence of familial combined hyperlipidemia. Apo E phenotypes and hyperlipidemia segregated independently. It is concluded that primary dysbetalipoproteinemia is a frequent monogenic variant of lipoprotein metabolism, but not a disease. Coincidence in one individual of genes for this specific dyslipoproteinemia with any of the genes for monogenic or polygenic forms of familial hyperlipidemia results in hyperlipoproteinemia type III. Hence hyperlipoproteinemia type III is caused by at least two non-allelic genes and is a polygenic disorder."}
{"id": "PMID:215365", "title": "Long-term administration of vitamin D steroles in incipient and advanced renal failure: effect on bone histology.", "content": "In 36 patients with incipient and advanced renal failure (CCr 80--30 ml/min X 1.73 m2), serum chemistry including ionized Ca, serum PTH and fractional intestinal absorption of Ca (whole body counter; two-dose-technique; 47Ca p.o. and i.v. to correct for urinary and endogenous fecal loss were measured. Quantitative bone histology after in vivo tetracycline double labeling was evaluated from undecalcified sections before and 18 months after therapy with vitamin D3 or 5,6-trans-25-OH-CC in a dose sufficient to raise intestinal absorption and/or urinary excretion of Ca. Intestinal absorption of Ca was impaired in some patients at a GFR of 60 ml/min/1.73 m2. After up to 10000 U/d 5,6-trans-25-OH-CC and 8000 IU/d vitamin D3, respectively, fractional intestinal absorption of Ca rose and was normalized in all patients. There was a concomitant rise in urinary Ca. Serum PTH fell, but did not always return into the normal range. Ionized Ca rose in all patients. Bone histology was evaluated in 17 of these 36 patients after informed consent was obtained. The mass of mineralized bone (Vv) rose in 7/17 patients, pointing to a positive calcium balance. Volumetric density of osteoid (Vvos) and surface density of osteoid (Svos) fell in 10/17 patients concomitant with an increase in the fraction of mineralizing seams and a decrease in the number of lamellae in osteoid seams. Osteoclastic resorption (OCl) fell as did the fraction of woven osteoid seams. However, woven osteoid failed to disappear completely and osteoclastic resorption stayed elevated in some patients. 5,6-trans-25-OH-CC and vitamin D3, in doses that normalized intestinal absorption of Ca, failed to restore completely bone histology to normal although mineralization and collagen texture of osteoid were consistently improved. The dose response characteristics to vitamin D of different abnormalities of Ca metabolism appear to be non-uniform.", "contents": "Long-term administration of vitamin D steroles in incipient and advanced renal failure: effect on bone histology. In 36 patients with incipient and advanced renal failure (CCr 80--30 ml/min X 1.73 m2), serum chemistry including ionized Ca, serum PTH and fractional intestinal absorption of Ca (whole body counter; two-dose-technique; 47Ca p.o. and i.v. to correct for urinary and endogenous fecal loss were measured. Quantitative bone histology after in vivo tetracycline double labeling was evaluated from undecalcified sections before and 18 months after therapy with vitamin D3 or 5,6-trans-25-OH-CC in a dose sufficient to raise intestinal absorption and/or urinary excretion of Ca. Intestinal absorption of Ca was impaired in some patients at a GFR of 60 ml/min/1.73 m2. After up to 10000 U/d 5,6-trans-25-OH-CC and 8000 IU/d vitamin D3, respectively, fractional intestinal absorption of Ca rose and was normalized in all patients. There was a concomitant rise in urinary Ca. Serum PTH fell, but did not always return into the normal range. Ionized Ca rose in all patients. Bone histology was evaluated in 17 of these 36 patients after informed consent was obtained. The mass of mineralized bone (Vv) rose in 7/17 patients, pointing to a positive calcium balance. Volumetric density of osteoid (Vvos) and surface density of osteoid (Svos) fell in 10/17 patients concomitant with an increase in the fraction of mineralizing seams and a decrease in the number of lamellae in osteoid seams. Osteoclastic resorption (OCl) fell as did the fraction of woven osteoid seams. However, woven osteoid failed to disappear completely and osteoclastic resorption stayed elevated in some patients. 5,6-trans-25-OH-CC and vitamin D3, in doses that normalized intestinal absorption of Ca, failed to restore completely bone histology to normal although mineralization and collagen texture of osteoid were consistently improved. The dose response characteristics to vitamin D of different abnormalities of Ca metabolism appear to be non-uniform."}
{"id": "PMID:215362", "title": "The effect of prazosin of pre- and post-synaptic alpha-receptors in the pithed rat.", "content": "1. Prazosin had a marked inhibitory effect on post-synaptic alpha-receptors in the pithed rat, as measured by the blood pressure response to the cumulative administration of clonidine. 2. Prazosin had no inhibitory effect, however, on the pre-synaptic alpha-receptor, as measured by the clonidine-induced reduction in the tachycardia produced by stimulation of the cardiac nerves. 3. These results suggest that prazosin has a selective antagonistic affinity for post-synaptic alpha-receptors.", "contents": "The effect of prazosin of pre- and post-synaptic alpha-receptors in the pithed rat. 1. Prazosin had a marked inhibitory effect on post-synaptic alpha-receptors in the pithed rat, as measured by the blood pressure response to the cumulative administration of clonidine. 2. Prazosin had no inhibitory effect, however, on the pre-synaptic alpha-receptor, as measured by the clonidine-induced reduction in the tachycardia produced by stimulation of the cardiac nerves. 3. These results suggest that prazosin has a selective antagonistic affinity for post-synaptic alpha-receptors."}
{"id": "PMID:215361", "title": "The effect of corticotrophin (ACTH) administration on the pressor action of angiotensin II, noradrenaline and tyramine in sheep.", "content": "1. Pressor responses to angiotensin II, noradrenaline and tyramine were examined in sheep prior to and during the development of corticotrophin-induced hypertension. 2. Pressor responses to angiotensin II amide did not change with corticotrophin (ACTH) administration. Small significant increases in pressor responses to noradrenaline occurred at low doses only (0.27 and 1.06 mumol/h). Significant increases in response to tyramine occurred after 24h  of ACTH administration, but were not maintained after 6 days of ACTH. These changes are quantitatively small and do not suggest that changes in pressor sensitivity contribute significantly to the rise in blood pressure following ACTH administration. 3. Sodium depletion significantly reduced the pressor responses to angiotensin II amide at all doses and to tyramine in the middle range only, but did not affect the responses to noradrenaline.", "contents": "The effect of corticotrophin (ACTH) administration on the pressor action of angiotensin II, noradrenaline and tyramine in sheep. 1. Pressor responses to angiotensin II, noradrenaline and tyramine were examined in sheep prior to and during the development of corticotrophin-induced hypertension. 2. Pressor responses to angiotensin II amide did not change with corticotrophin (ACTH) administration. Small significant increases in pressor responses to noradrenaline occurred at low doses only (0.27 and 1.06 mumol/h). Significant increases in response to tyramine occurred after 24h  of ACTH administration, but were not maintained after 6 days of ACTH. These changes are quantitatively small and do not suggest that changes in pressor sensitivity contribute significantly to the rise in blood pressure following ACTH administration. 3. Sodium depletion significantly reduced the pressor responses to angiotensin II amide at all doses and to tyramine in the middle range only, but did not affect the responses to noradrenaline."}
{"id": "PMID:215369", "title": "Poorly differentiated lymphocytic lymphoma with ectopic parathormone production: visulization of metastatic calcification by bone scan.", "content": "Metastatic soft tissue calcification is known to occur in hypercalcemia and is usually present in the kidneys, stomach and lungs. 1--3 This case presents two unusual features: 1) ectopic parathormone production in association with poorly differentiated lymphocytic lymphoma; and and 2) uptake of 99mTc-pyrophosphate in the liver in the absence of demonstrable abnormality at autopsy. The more usual sites of metastatic calcification also showed uptake of the radionuclide. We will discuss metastatic soft tissue calcification, ectopic parathyroid hormone production, hypercalcemia in malignancy and bone scan agent localization in soft tissues.", "contents": "Poorly differentiated lymphocytic lymphoma with ectopic parathormone production: visulization of metastatic calcification by bone scan. Metastatic soft tissue calcification is known to occur in hypercalcemia and is usually present in the kidneys, stomach and lungs. 1--3 This case presents two unusual features: 1) ectopic parathormone production in association with poorly differentiated lymphocytic lymphoma; and and 2) uptake of 99mTc-pyrophosphate in the liver in the absence of demonstrable abnormality at autopsy. The more usual sites of metastatic calcification also showed uptake of the radionuclide. We will discuss metastatic soft tissue calcification, ectopic parathyroid hormone production, hypercalcemia in malignancy and bone scan agent localization in soft tissues."}
{"id": "PMID:215366", "title": "Paraplegia, syringomyelia tarda and neuropathic arthrosis of the shoulder: a triad.", "content": "A casually related triad of syringomyelia tarda, postparaplegia with secondary neuropathic arthrosis of the shoulder has been presented. The development of neuropathic arthrosis of the shoulder has been presented. The development of neuropathic arthrosis of the shoulder in 2 of our paraplegic patients prompted us to look for a correlation and/or a common etiology. Paraplegia secondary to spinal cord injury could be causative or at least an associated factor in a delayed proximal syringomyelia. It is the syringomyelia which can lead to the neuropathic arthrosis in the upper extremity, mainly, in the shoulder. There is an interesting pathological association of paraplegia and syringomyelia with neuropathic arthrosis. Earlier awareness of any neurological changes in the upper extremity of the paraplegic patient could point to recognition of syringomyelic process and portend a tendency toward neuropathic arthrosis of the shoulder. This would require a high index of suspicion, and subsequently a preventative, protective orthopedic approach to minimize the usual functional deformity that occurs when this neuropathy involves the shoulder.", "contents": "Paraplegia, syringomyelia tarda and neuropathic arthrosis of the shoulder: a triad. A casually related triad of syringomyelia tarda, postparaplegia with secondary neuropathic arthrosis of the shoulder has been presented. The development of neuropathic arthrosis of the shoulder has been presented. The development of neuropathic arthrosis of the shoulder in 2 of our paraplegic patients prompted us to look for a correlation and/or a common etiology. Paraplegia secondary to spinal cord injury could be causative or at least an associated factor in a delayed proximal syringomyelia. It is the syringomyelia which can lead to the neuropathic arthrosis in the upper extremity, mainly, in the shoulder. There is an interesting pathological association of paraplegia and syringomyelia with neuropathic arthrosis. Earlier awareness of any neurological changes in the upper extremity of the paraplegic patient could point to recognition of syringomyelic process and portend a tendency toward neuropathic arthrosis of the shoulder. This would require a high index of suspicion, and subsequently a preventative, protective orthopedic approach to minimize the usual functional deformity that occurs when this neuropathy involves the shoulder."}
{"id": "PMID:215363", "title": "Inhibition of human pulmonary phosphodiesterase activity by therapeutic levels of theophylline.", "content": "1. To test the hypothesis that inhibition of cyclic nucleotide phosphodiesterase is the major mechanism of the bronchodilator action of theophylline in reversible airways disease, the effects of therapeutic plasma levels of the drug on human pulmonary phosphodiesterase activity were examined. 2. Therapeutic levels of theophylline inhibited the phosphodiesterase-catalysed hydrolysis of adenosine cyclic 3',5'-monophosphate (cAMP) and guanosine cyclic 3',5'-monophosphate (cGMP), but the percentage inhibition was relatively small. 3. The results, while supporting the assumed contribution of phosphodiesterase inhibition to the overall mechanism of theophylline action, suggest that other presently unknown factors must also be taken into consideration to fully explain the beneficial effects of theophylline in reversible airways disease.", "contents": "Inhibition of human pulmonary phosphodiesterase activity by therapeutic levels of theophylline. 1. To test the hypothesis that inhibition of cyclic nucleotide phosphodiesterase is the major mechanism of the bronchodilator action of theophylline in reversible airways disease, the effects of therapeutic plasma levels of the drug on human pulmonary phosphodiesterase activity were examined. 2. Therapeutic levels of theophylline inhibited the phosphodiesterase-catalysed hydrolysis of adenosine cyclic 3',5'-monophosphate (cAMP) and guanosine cyclic 3',5'-monophosphate (cGMP), but the percentage inhibition was relatively small. 3. The results, while supporting the assumed contribution of phosphodiesterase inhibition to the overall mechanism of theophylline action, suggest that other presently unknown factors must also be taken into consideration to fully explain the beneficial effects of theophylline in reversible airways disease."}
{"id": "PMID:215367", "title": "Suprascapular axonotmesis and rheumatoid disease: report of a case treated conservatively.", "content": "Axonotmesis of the suprascapular nerve mimics rupture of the musculotendinous cuff of the shoulder. Arthrography of the shoulder joint and electromyographic studies of the shoulder muscles are essential in arriving at the proper diagnosis. Axonotmesis of the suprascapular nerve should be suspected in the patient who presents with signs of ruptured musculotendinous cuff and who has a normal arthrogram.", "contents": "Suprascapular axonotmesis and rheumatoid disease: report of a case treated conservatively. Axonotmesis of the suprascapular nerve mimics rupture of the musculotendinous cuff of the shoulder. Arthrography of the shoulder joint and electromyographic studies of the shoulder muscles are essential in arriving at the proper diagnosis. Axonotmesis of the suprascapular nerve should be suspected in the patient who presents with signs of ruptured musculotendinous cuff and who has a normal arthrogram."}
{"id": "PMID:215364", "title": "Decreased cardiac beta-adrenoceptors in hypertensive rats.", "content": "1. beta-Adrenoceptors have been investigated in cardiac and renal cell membranes from hypertensive and normal rats. 2. The 125I-labelled beta-adrenoceptor antagonist 1-(4-iodophenoxy)-3-isopropylaminopropan-2-ol was used to measure directly the number and affinity of receptors. 3. Cardiac membranes from hypertensive rats had a lower concentration of beta-adrenoceptors than membranes from control normotensive animals, but the affinities of the receptors remained unchanged. Receptor concentration decreased by half and was similar in each of the three models of experimental hypertension investigated. 4. In contrast, kidney membranes from hypertensive animals had the same beta-adrenoceptor concentration and affinity as membranes from normotensive rats. 5. The decrease in cardiac beta-adrenoceptor concentration may reflect an increase in cardiac sympathetic drive in these experimental hypertensive models.", "contents": "Decreased cardiac beta-adrenoceptors in hypertensive rats. 1. beta-Adrenoceptors have been investigated in cardiac and renal cell membranes from hypertensive and normal rats. 2. The 125I-labelled beta-adrenoceptor antagonist 1-(4-iodophenoxy)-3-isopropylaminopropan-2-ol was used to measure directly the number and affinity of receptors. 3. Cardiac membranes from hypertensive rats had a lower concentration of beta-adrenoceptors than membranes from control normotensive animals, but the affinities of the receptors remained unchanged. Receptor concentration decreased by half and was similar in each of the three models of experimental hypertension investigated. 4. In contrast, kidney membranes from hypertensive animals had the same beta-adrenoceptor concentration and affinity as membranes from normotensive rats. 5. The decrease in cardiac beta-adrenoceptor concentration may reflect an increase in cardiac sympathetic drive in these experimental hypertensive models."}
{"id": "PMID:215371", "title": "Poliomyelitis in the fetus and the newborn. A comment on the new understanding of the pathogenesis.", "content": "A survey of the literature shows that although poliovirus may be recovered from fetuses whose mothers have paralytic poliomyelitis, there is no evidence that the fetuses themselves are affected. It is suggested that if postnatal poliomyelitis results from an autoallergic response not developed in the fetus, then poliovirus cannot enter the CNS of the fetus. When a mother has paralytic poliomyelitis at delivery the neonate has a 40 per cent chance of poliomyelitis, with a case fatality rate of about 50 per cent. It is suggested that most of these neonates become infected by virus entry into the exposed olfactory and nasal nerve endings after the membranes have burst. This would explain the very short incubation period and the high case and case fatality rates.", "contents": "Poliomyelitis in the fetus and the newborn. A comment on the new understanding of the pathogenesis. A survey of the literature shows that although poliovirus may be recovered from fetuses whose mothers have paralytic poliomyelitis, there is no evidence that the fetuses themselves are affected. It is suggested that if postnatal poliomyelitis results from an autoallergic response not developed in the fetus, then poliovirus cannot enter the CNS of the fetus. When a mother has paralytic poliomyelitis at delivery the neonate has a 40 per cent chance of poliomyelitis, with a case fatality rate of about 50 per cent. It is suggested that most of these neonates become infected by virus entry into the exposed olfactory and nasal nerve endings after the membranes have burst. This would explain the very short incubation period and the high case and case fatality rates."}
{"id": "PMID:215372", "title": "Alterations of adrenal and uterine angiotensin II receptors during variation of sodium intake and/or experimental hypertension.", "content": "1. Angiotensin II receptors from rat adrenal gland and myometrium were studied during variation of sodium intake. 2. In both target-tissues low Na+ diet increased the number of receptors whereas a high Na+ diet did not modify the adrenocortical receptors but increased the number of uterine receptors. 3. Deoxycorticosterone and one kidney Goldblatt hypertension were associated with a decrease in the number of adrenal receptors. 4. Alterations of angiotensin II receptors alone cannot explain satisfactorily the variations of sensitivity of target-cells to angiotensin II during sodium balance changes.", "contents": "Alterations of adrenal and uterine angiotensin II receptors during variation of sodium intake and/or experimental hypertension. 1. Angiotensin II receptors from rat adrenal gland and myometrium were studied during variation of sodium intake. 2. In both target-tissues low Na+ diet increased the number of receptors whereas a high Na+ diet did not modify the adrenocortical receptors but increased the number of uterine receptors. 3. Deoxycorticosterone and one kidney Goldblatt hypertension were associated with a decrease in the number of adrenal receptors. 4. Alterations of angiotensin II receptors alone cannot explain satisfactorily the variations of sensitivity of target-cells to angiotensin II during sodium balance changes."}
{"id": "PMID:215373", "title": "Tonin--angiotensin II system in hypertension.", "content": "1. A single intravenous administration of rabbit tonin antiserum into one-kidney one-clip hypertensive rats restored blood pressure to normal in seven out of ten animals. There was little change in blood pressure in two-kidney one-clip hypertensive, uninephrectomized or sham-operated rats. 2. Infusion of tonin in control rats did not modify arterial blood pressure. However, in indomethacin salt-treated rats a marked increase in arterial blood pressure was observed under tonin infusion. 3. Plasma tonin activity was significantly increased in human essential and renovascular hypertension. 4. These findings strongly suggest that tonin is important in the maintenance of high blood pressure. However, other factors (possibly prostaglandins and sodium) have to be modified in order to activate the tonin--angiotensin II system.", "contents": "Tonin--angiotensin II system in hypertension. 1. A single intravenous administration of rabbit tonin antiserum into one-kidney one-clip hypertensive rats restored blood pressure to normal in seven out of ten animals. There was little change in blood pressure in two-kidney one-clip hypertensive, uninephrectomized or sham-operated rats. 2. Infusion of tonin in control rats did not modify arterial blood pressure. However, in indomethacin salt-treated rats a marked increase in arterial blood pressure was observed under tonin infusion. 3. Plasma tonin activity was significantly increased in human essential and renovascular hypertension. 4. These findings strongly suggest that tonin is important in the maintenance of high blood pressure. However, other factors (possibly prostaglandins and sodium) have to be modified in order to activate the tonin--angiotensin II system."}
{"id": "PMID:215374", "title": "Long-term treatment of hypertension in man by an orally active angiotensin-converting enzyme inhibitor.", "content": "1. Captopril or SQ 14 225, administered orally twice a day, reduced the blood pressure of hypertensive patients whatever their clinical diagnosis and even when their plasma renin activity was 'normal' or low. 2. Long-term administration of captopril, either alone or together with diuretics, provides a powerful new tool with which to treat ambulatory hypertensive patients. 3. The renin system may play an important role in maintaining blood pressure in a majority of hypertensive patients.", "contents": "Long-term treatment of hypertension in man by an orally active angiotensin-converting enzyme inhibitor. 1. Captopril or SQ 14 225, administered orally twice a day, reduced the blood pressure of hypertensive patients whatever their clinical diagnosis and even when their plasma renin activity was 'normal' or low. 2. Long-term administration of captopril, either alone or together with diuretics, provides a powerful new tool with which to treat ambulatory hypertensive patients. 3. The renin system may play an important role in maintaining blood pressure in a majority of hypertensive patients."}
{"id": "PMID:215375", "title": "Altered activity of the sodium-potassium pump in arteries of rats with steroid hypertension.", "content": "1. Ouabain-sensitive uptake of 86Rb, a measure of the Na+-K+ pump activity, was studied in tail arteries of rats made hypertensive with deoxycorticosterone and saline. 2. Decreased activity of the ouabain-sensitive Na+-K+ pump supports the hypothesis that the activity of Na+-K+ pump is suppressed in volume expanded hypertension.", "contents": "Altered activity of the sodium-potassium pump in arteries of rats with steroid hypertension. 1. Ouabain-sensitive uptake of 86Rb, a measure of the Na+-K+ pump activity, was studied in tail arteries of rats made hypertensive with deoxycorticosterone and saline. 2. Decreased activity of the ouabain-sensitive Na+-K+ pump supports the hypothesis that the activity of Na+-K+ pump is suppressed in volume expanded hypertension."}
{"id": "PMID:215377", "title": "Computed tomography of the paranasal sinuses, nasopharynx, and soft tissues of the neck.", "content": "A number of cases are presented illustrating the value of computed tomography in the investigation of mass lesions involving the paranasal sinuses, nasopharynx, and soft tissues of the neck. Rapid advances in CT technology now underway will alter our approach to the investigation of certain diseases in these locations.", "contents": "Computed tomography of the paranasal sinuses, nasopharynx, and soft tissues of the neck. A number of cases are presented illustrating the value of computed tomography in the investigation of mass lesions involving the paranasal sinuses, nasopharynx, and soft tissues of the neck. Rapid advances in CT technology now underway will alter our approach to the investigation of certain diseases in these locations."}
{"id": "PMID:215383", "title": "Activated oxygen species and oxidation of food constituents.", "content": "Activated oxygen species which may be important in initiating oxidative changes in foods include singlet oxygen, hydroxyl radical, ozone, superoxide anion (perhydroxyl radical at low pH), and hydrogen peroxide. Chemical and enzymic reactions known to occur in biological materials can generate singlet oxygen, hydroxyl radical, superoxide anion, and hydrogen peroxide. Ozone is primarily a product of photoreactions in polluted air. Reactions involving singlet oxygen, hydroxyl radical, and ozone with food constituents can ultimately yield peroxides which decompose to initiate oxidative chain reactions. Superoxide anion and hydrogen peroxide are relatively inert toward organic molecules but can decompose to produce the more reactive singlet oxygen and hydroxyl radical. Inhibition of reactions initiated by reactive oxygen species in foods should be very important in preserving the oxidative stability of foods. The generation, detection, measurement, reaction, and inhibition of reactions of active oxygen species are surveyed in this review.", "contents": "Activated oxygen species and oxidation of food constituents. Activated oxygen species which may be important in initiating oxidative changes in foods include singlet oxygen, hydroxyl radical, ozone, superoxide anion (perhydroxyl radical at low pH), and hydrogen peroxide. Chemical and enzymic reactions known to occur in biological materials can generate singlet oxygen, hydroxyl radical, superoxide anion, and hydrogen peroxide. Ozone is primarily a product of photoreactions in polluted air. Reactions involving singlet oxygen, hydroxyl radical, and ozone with food constituents can ultimately yield peroxides which decompose to initiate oxidative chain reactions. Superoxide anion and hydrogen peroxide are relatively inert toward organic molecules but can decompose to produce the more reactive singlet oxygen and hydroxyl radical. Inhibition of reactions initiated by reactive oxygen species in foods should be very important in preserving the oxidative stability of foods. The generation, detection, measurement, reaction, and inhibition of reactions of active oxygen species are surveyed in this review."}
{"id": "PMID:215386", "title": "Decubitus ulcers: a comparative study.", "content": "Seventeen patients with thirty-four decubitus ulcers were treated with dextranomer, collagenase, or sugar and egg white. All seven patients in the dextranomer group and two of five patients in the collagenase group improved at the end of the study, but none of the five patients on sugar and egg white treatment improved. Although collagenase can be helpful in the treatment of decubitus ulcers, dextranomer is significantly better.", "contents": "Decubitus ulcers: a comparative study. Seventeen patients with thirty-four decubitus ulcers were treated with dextranomer, collagenase, or sugar and egg white. All seven patients in the dextranomer group and two of five patients in the collagenase group improved at the end of the study, but none of the five patients on sugar and egg white treatment improved. Although collagenase can be helpful in the treatment of decubitus ulcers, dextranomer is significantly better."}
{"id": "PMID:215387", "title": "Effect of metal ions on growth and sporulation of Clostridium perfringens in a synthetic medium.", "content": "All cells, whatever their origin, function in an essentially inorganic environment. In this environment, metal cations play an important role. Attempts were made in the present study to determine if different amounts of five metal ions (MG++, Fe++, Mn++, Zn++, Ca++) are needed for secondary metabolism of Clostridium perfringens than are needed for primary metabolism. Both the vegetative growth stage (primary metabolic stage) and spore stage (secondary metabolic stage) of Clostridium perfringens were studied. Endeavors were made to detect the effects of metal ions, if any, on growth and sporulation of the organisms. Mg++ was required for growth of vegetative cells and maintenance of normal cellular morphology, Fe++ was needed for sporulation as well as for vegetative growth, but the amount needed for spore formation was higher than that needed for growth. Ca++ was essential to refractility and heat-resistance of spores. Zn++ inhibited both growth and sporulation, if the Mg++ concentration was low. Mn++ was required for neither growth nor sporulation. For maximum heat-resistance of the spores, Ca++ plus unidentified organic substances were required.", "contents": "Effect of metal ions on growth and sporulation of Clostridium perfringens in a synthetic medium. All cells, whatever their origin, function in an essentially inorganic environment. In this environment, metal cations play an important role. Attempts were made in the present study to determine if different amounts of five metal ions (MG++, Fe++, Mn++, Zn++, Ca++) are needed for secondary metabolism of Clostridium perfringens than are needed for primary metabolism. Both the vegetative growth stage (primary metabolic stage) and spore stage (secondary metabolic stage) of Clostridium perfringens were studied. Endeavors were made to detect the effects of metal ions, if any, on growth and sporulation of the organisms. Mg++ was required for growth of vegetative cells and maintenance of normal cellular morphology, Fe++ was needed for sporulation as well as for vegetative growth, but the amount needed for spore formation was higher than that needed for growth. Ca++ was essential to refractility and heat-resistance of spores. Zn++ inhibited both growth and sporulation, if the Mg++ concentration was low. Mn++ was required for neither growth nor sporulation. For maximum heat-resistance of the spores, Ca++ plus unidentified organic substances were required."}
{"id": "PMID:215388", "title": "Cholinergic mechanisms and short-term potentiation.", "content": "Acutely prepared rabbits were used to study, electrophysiologically, tetanic and post-tetanic potentiation of the pathway from the medial septal region to hippocampal field CA1. It was found that tetanic potentiation, evoked by short stimulus trains, was maximal at 6--8 Hz. Responses recovered from post-tetanic potentiation in 5--35 seconds. Acetylcholine, physostigmine, and cyclic GMP each had an excitatory effect on pyramidal cell responses when applied in stratum radiatum. The time course studies showed that these effects outlasted the duration of the injection current by many minutes. Phosphodiesterase inhibitors (e.g., isobutyl methyl xanthine) prolonged the time course of recovery with test responses which were post-tetanically potentiated. K+, on the other hand, selectively enhanced tetanic potentiation. It is suggested, with respect to the potentiation phenomena, that K+ acted primarily presynaptically to facilitate transmitter release, whereas cyclic GMP acted primarily postsynaptically for the enhancement of pyramidal cell excitability.", "contents": "Cholinergic mechanisms and short-term potentiation. Acutely prepared rabbits were used to study, electrophysiologically, tetanic and post-tetanic potentiation of the pathway from the medial septal region to hippocampal field CA1. It was found that tetanic potentiation, evoked by short stimulus trains, was maximal at 6--8 Hz. Responses recovered from post-tetanic potentiation in 5--35 seconds. Acetylcholine, physostigmine, and cyclic GMP each had an excitatory effect on pyramidal cell responses when applied in stratum radiatum. The time course studies showed that these effects outlasted the duration of the injection current by many minutes. Phosphodiesterase inhibitors (e.g., isobutyl methyl xanthine) prolonged the time course of recovery with test responses which were post-tetanically potentiated. K+, on the other hand, selectively enhanced tetanic potentiation. It is suggested, with respect to the potentiation phenomena, that K+ acted primarily presynaptically to facilitate transmitter release, whereas cyclic GMP acted primarily postsynaptically for the enhancement of pyramidal cell excitability."}
{"id": "PMID:215389", "title": "Neuronal aspects of septo-hippocampal relations.", "content": "In unanaesthetized, conscious rabbits, in unstressful conditions, the neurons of the hippocampus and septum were investigated extracellularly during the presentation of a series of varied sensory stimuli. In the normal hippocampus these stimuli evoke habituating reactions of tonic (more usually, inhibitory) type in field CA3, with the addition of 'specific' patterned, and phasic reactions in field CA1. After complete septo-hippocampal disconnection the proportion of tonic (especially, of inhibitory) reactions in the hippocampus decreases. Theta bursts in the neuronal activity are absent; reactions to repeated sensory stimuli do not habituate. After lesion of the cortical perforant path to the hippocampus the majority of reactions in both fields are of tonic type. The proportion of neurons with regular theta bursts increases. Habituation is completely absent. A high correlation appears between the sensory reactions and the effects of midbrain reticular formation stimulation in the same neurons. The combination of both lesions does not significantly change the spontaneous activity of hippocampal neurons (except for the absence of the theta bursts). An increase in the level of activity of hippocampal neurons (by physostigmine), or rhythmic stimulation of the remaining synaptic systems, does not restore their rhythmic theta activity. In the septum deprived of hippocampal input the normal level of reactivity to sensory stimuli and the normal types of reaction are preserved. The proportion of neurons with theta bursts increases. The typical linear and rapid habituation of reactions disappears and is replaced by an unlimited increment in effects during repeated presentations of sensory stimuli. Discussion concerns the synchronizing and inhibitory influences of the septum on the hippocampus, and the role of the hippocampus in the organization of decremental processes (habituation) in the septum and brainstem structures.", "contents": "Neuronal aspects of septo-hippocampal relations. In unanaesthetized, conscious rabbits, in unstressful conditions, the neurons of the hippocampus and septum were investigated extracellularly during the presentation of a series of varied sensory stimuli. In the normal hippocampus these stimuli evoke habituating reactions of tonic (more usually, inhibitory) type in field CA3, with the addition of 'specific' patterned, and phasic reactions in field CA1. After complete septo-hippocampal disconnection the proportion of tonic (especially, of inhibitory) reactions in the hippocampus decreases. Theta bursts in the neuronal activity are absent; reactions to repeated sensory stimuli do not habituate. After lesion of the cortical perforant path to the hippocampus the majority of reactions in both fields are of tonic type. The proportion of neurons with regular theta bursts increases. Habituation is completely absent. A high correlation appears between the sensory reactions and the effects of midbrain reticular formation stimulation in the same neurons. The combination of both lesions does not significantly change the spontaneous activity of hippocampal neurons (except for the absence of the theta bursts). An increase in the level of activity of hippocampal neurons (by physostigmine), or rhythmic stimulation of the remaining synaptic systems, does not restore their rhythmic theta activity. In the septum deprived of hippocampal input the normal level of reactivity to sensory stimuli and the normal types of reaction are preserved. The proportion of neurons with theta bursts increases. The typical linear and rapid habituation of reactions disappears and is replaced by an unlimited increment in effects during repeated presentations of sensory stimuli. Discussion concerns the synchronizing and inhibitory influences of the septum on the hippocampus, and the role of the hippocampus in the organization of decremental processes (habituation) in the septum and brainstem structures."}
{"id": "PMID:215390", "title": "Long-lasting facilitation of synaptic transmission.", "content": "After tetanization of several hippocampal pathways (10--50 Hz for 5--15 seconds) there is an increased synaptic transmission of long duration (long-lasting facilitation). The present investigation was undertaken on isolated hippocampal slices to study the mechanism of the effect. The transverse hippocampal slice preparation in vitro allows the simultaneous testing of several afferent fibre systems on the same cell or population of cells. Tetanization of one group of afferent fibres to CA1 pyramids was followed by a long-lasting increase of synaptic transmission along the same fibres, whereas a control input line gave unchanged responses. Using the presynaptic volley as an indicator of the number of afferent impulses, the increased synaptic transmission appeared as an increased excitatory postsynaptic potential (EPSP), increased amplitude and reduced latency of the population spike, and an increased probability of firing of single units. Intracellular recording showed increased EPSPs to afferents of the tetanized line, but no lasting change in membrane resistance or in the response to a depolarizing current pulse. Thus, the effect cannot be ascribed to a general postsynaptic excitability increase. The specific changes in the synaptic transmission may be due either to an increased amount of liberated transmitter or to a local postsynaptic change near the tetanized synapses.", "contents": "Long-lasting facilitation of synaptic transmission. After tetanization of several hippocampal pathways (10--50 Hz for 5--15 seconds) there is an increased synaptic transmission of long duration (long-lasting facilitation). The present investigation was undertaken on isolated hippocampal slices to study the mechanism of the effect. The transverse hippocampal slice preparation in vitro allows the simultaneous testing of several afferent fibre systems on the same cell or population of cells. Tetanization of one group of afferent fibres to CA1 pyramids was followed by a long-lasting increase of synaptic transmission along the same fibres, whereas a control input line gave unchanged responses. Using the presynaptic volley as an indicator of the number of afferent impulses, the increased synaptic transmission appeared as an increased excitatory postsynaptic potential (EPSP), increased amplitude and reduced latency of the population spike, and an increased probability of firing of single units. Intracellular recording showed increased EPSPs to afferents of the tetanized line, but no lasting change in membrane resistance or in the response to a depolarizing current pulse. Thus, the effect cannot be ascribed to a general postsynaptic excitability increase. The specific changes in the synaptic transmission may be due either to an increased amount of liberated transmitter or to a local postsynaptic change near the tetanized synapses."}
{"id": "PMID:215391", "title": "Polypeptide hormone-receptor interactions: the structure and receptor binding of insulin and glucagon.", "content": "Insulin is a small globular protein with a well defined tertiary structure which is closely similar in all species with the exception of certain hystricomorphs such as the guinea pig. Insulin-like growth factor is homologous with insulin and probably has an insulin-like tertiary structure. In contrast glucagon is not a globular protein. It exists as an equilibrium population of conformers with low helix content at physiological concentrations but attains a largely helical conformation on association to trimers. The receptor binding of insulin depends critically on the correct three-dimensional juxtaposition of groups (A1, A21, B25, etc) and involves both hydrophobic and polar interactions. In insulin-like growth factor part of the insulin receptor region is thought to be buried in extra peptide, so explaining its weak binding to insulin receptors. In contrast the glucagon receptor complex probably involves largely hydrophobic contacts which are possible when a helical conformer is formed.", "contents": "Polypeptide hormone-receptor interactions: the structure and receptor binding of insulin and glucagon. Insulin is a small globular protein with a well defined tertiary structure which is closely similar in all species with the exception of certain hystricomorphs such as the guinea pig. Insulin-like growth factor is homologous with insulin and probably has an insulin-like tertiary structure. In contrast glucagon is not a globular protein. It exists as an equilibrium population of conformers with low helix content at physiological concentrations but attains a largely helical conformation on association to trimers. The receptor binding of insulin depends critically on the correct three-dimensional juxtaposition of groups (A1, A21, B25, etc) and involves both hydrophobic and polar interactions. In insulin-like growth factor part of the insulin receptor region is thought to be buried in extra peptide, so explaining its weak binding to insulin receptors. In contrast the glucagon receptor complex probably involves largely hydrophobic contacts which are possible when a helical conformer is formed."}
{"id": "PMID:215392", "title": "The free radical in ribonucleotide reductase from E. coli.", "content": "Protein B2, one of the subunits of ribonucleotide reductase from Escherichia coli, contains a stable free radical. It is characterized by a doublet e.p.r. signal centered around g = 2.0047 and a sharp peak at 410 nm in the optical spectrum. The radical has been assigned to a tyrosyl residue in the protein with its spin density delocalized over the aromatic ring. Protein B2 also contains two antiferromagnetically-coupled high-spin iron(III) atoms, which stabilize the free radical. Protein B1, the other subunit of ribonucleotide reductase, contains two binding sites for substrate molecules, which are the four common ribonucleoside diphosphates. It also contains two classes of allosteric effector-binding sites. ATP and deoxyribonucleoside triphosphates function as effectors. A one-to-one complex of proteins B1 and B2 forms the enzymically-active ribonucleotide reductase. The free radical is, most likely, part of the active site.", "contents": "The free radical in ribonucleotide reductase from E. coli. Protein B2, one of the subunits of ribonucleotide reductase from Escherichia coli, contains a stable free radical. It is characterized by a doublet e.p.r. signal centered around g = 2.0047 and a sharp peak at 410 nm in the optical spectrum. The radical has been assigned to a tyrosyl residue in the protein with its spin density delocalized over the aromatic ring. Protein B2 also contains two antiferromagnetically-coupled high-spin iron(III) atoms, which stabilize the free radical. Protein B1, the other subunit of ribonucleotide reductase, contains two binding sites for substrate molecules, which are the four common ribonucleoside diphosphates. It also contains two classes of allosteric effector-binding sites. ATP and deoxyribonucleoside triphosphates function as effectors. A one-to-one complex of proteins B1 and B2 forms the enzymically-active ribonucleotide reductase. The free radical is, most likely, part of the active site."}
{"id": "PMID:215393", "title": "The chemical properties of out-of-equilibrium states of proteins and the role of these states in protein functioning.", "content": "The out-of-equilibrium states of several iron-containing proteins (cytochromes c of different origin, haemoglobin, myoglobin, ferredoxin and other non-haem iron proteins, cytochrome c oxidase, horseradish peroxidase) were recorded after fast changes in the active centre (electron reduction of iron, ligand dissociation). Strained states result in which the active centre has already been changed and undergone vibrational relaxation but the main part of protein globule is in the 'old', now out-of-equilibrium, state. Protein structure and chemical properties in these states differ considerably from those in equilibrium states. As a rule, the rate constants of protein-specific chemical reactions increase in out-of-equilibrium states by 1--3 orders of magnitude in comparison with those in equilibrium states. Spectra and reactivity of these proteins change in the course of slow (up to 10(-1) s) conformational relaxation, continuously approaching the equilibrium values. It seems that this conformational relaxation is essentially the elementary act of many enzymic reactions for which the rate of substrate-product transformation is determined by the rate of this conformational change.", "contents": "The chemical properties of out-of-equilibrium states of proteins and the role of these states in protein functioning. The out-of-equilibrium states of several iron-containing proteins (cytochromes c of different origin, haemoglobin, myoglobin, ferredoxin and other non-haem iron proteins, cytochrome c oxidase, horseradish peroxidase) were recorded after fast changes in the active centre (electron reduction of iron, ligand dissociation). Strained states result in which the active centre has already been changed and undergone vibrational relaxation but the main part of protein globule is in the 'old', now out-of-equilibrium, state. Protein structure and chemical properties in these states differ considerably from those in equilibrium states. As a rule, the rate constants of protein-specific chemical reactions increase in out-of-equilibrium states by 1--3 orders of magnitude in comparison with those in equilibrium states. Spectra and reactivity of these proteins change in the course of slow (up to 10(-1) s) conformational relaxation, continuously approaching the equilibrium values. It seems that this conformational relaxation is essentially the elementary act of many enzymic reactions for which the rate of substrate-product transformation is determined by the rate of this conformational change."}
{"id": "PMID:215394", "title": "Coenzyme-induced conformational changes and substrate binding in liver alcohol dehydrogenase.", "content": "The apoenzyme and holoenzyme structures of liver alcohol dehydrogenase have been determined by X-ray methods to obtain details about coenzyme binding, substrate specificity and the catalytic mechanism. Coenzyme binding induces a conformational change of the protein which partly shields the active site from the solution. The reduced coenzyme binds in an open conformation similar to that of NAD bound to malate dehydrogenase. A hydrogen bond between Thr-178 and the carboxamide group of the coenzyme is essential for proper positioning of the nicotinamide in the active site. Coenzyme analogues in which the carboxamide group is absent or substituted with iodine bind in a different conformation and do not induce the structural change of the protein. Binding of substrate molecules has been studied in crystals obtained from an equilibrium mixture of enzyme, coenzyme and p-bromobenzyl alcohol. The oxygen atom of this substrate as well as that of the inhibitor molecules trifluoroethanol and dimethyl sulphoxide bind directly to the catalytic zinc atom. The substrate-binding region is a deep hydrophobic pocket at the bottom of which the zinc atom mediates electrophilic catalysis of alcohol oxidation.", "contents": "Coenzyme-induced conformational changes and substrate binding in liver alcohol dehydrogenase. The apoenzyme and holoenzyme structures of liver alcohol dehydrogenase have been determined by X-ray methods to obtain details about coenzyme binding, substrate specificity and the catalytic mechanism. Coenzyme binding induces a conformational change of the protein which partly shields the active site from the solution. The reduced coenzyme binds in an open conformation similar to that of NAD bound to malate dehydrogenase. A hydrogen bond between Thr-178 and the carboxamide group of the coenzyme is essential for proper positioning of the nicotinamide in the active site. Coenzyme analogues in which the carboxamide group is absent or substituted with iodine bind in a different conformation and do not induce the structural change of the protein. Binding of substrate molecules has been studied in crystals obtained from an equilibrium mixture of enzyme, coenzyme and p-bromobenzyl alcohol. The oxygen atom of this substrate as well as that of the inhibitor molecules trifluoroethanol and dimethyl sulphoxide bind directly to the catalytic zinc atom. The substrate-binding region is a deep hydrophobic pocket at the bottom of which the zinc atom mediates electrophilic catalysis of alcohol oxidation."}
{"id": "PMID:215395", "title": "The consequences of nucleotide binding to liver alcohol dehydrogenase.", "content": "Extensive and informative steady-state kinetic investigations of the mechanisms of horse liver alcohol dehydrogenase have recently been complemented by observations of the fluorescence and spectroscopic characteristics of transient intermediates by rapid-reaction techniques. In this way it was possible to study separately steps involved during enzyme-substrate complex formation and during the catalytic process. It can be shown that a proton is liberated during complex formation before the transfer of a hydride ion from ethanol to form NADH. This must be due to a change in pK of a group on the enzyme protein and is linked to a change in tryptophan fluorescence. Pressure relaxation techniques have enabled us to study the rate constants of the change in tryptophan fluorescence linked to NAD+ binding and proton dissociation. We have shown that NAD+ binding occurs in two steps: a rapid secondorder association, followed by the substrate-induced isomerization to form the reactive enzyme-substrate intermediate. The isomerization rate constants were determined in both directions and their role in the overall reaction mechanism could be identified.", "contents": "The consequences of nucleotide binding to liver alcohol dehydrogenase. Extensive and informative steady-state kinetic investigations of the mechanisms of horse liver alcohol dehydrogenase have recently been complemented by observations of the fluorescence and spectroscopic characteristics of transient intermediates by rapid-reaction techniques. In this way it was possible to study separately steps involved during enzyme-substrate complex formation and during the catalytic process. It can be shown that a proton is liberated during complex formation before the transfer of a hydride ion from ethanol to form NADH. This must be due to a change in pK of a group on the enzyme protein and is linked to a change in tryptophan fluorescence. Pressure relaxation techniques have enabled us to study the rate constants of the change in tryptophan fluorescence linked to NAD+ binding and proton dissociation. We have shown that NAD+ binding occurs in two steps: a rapid secondorder association, followed by the substrate-induced isomerization to form the reactive enzyme-substrate intermediate. The isomerization rate constants were determined in both directions and their role in the overall reaction mechanism could be identified."}
{"id": "PMID:215398", "title": "Uptake, distribution, and elimination of sodium linear alkylbenzene sulfonate and sodium alkyl sulfate in carp.", "content": "Uptake, distribution, and elimination of labeled surfactants, 35S-labeled sodium laurylbenzenesulfonate (35S-C12-LAS) and 35S-labeled sodium lauryl sulfate (35S-C12-AS), were investigated in carp exposed to a low concentration level of the respective solutions found in river water in Japan by whole-body autoradiography and liquid scintillation counting. Whole-body autoradiograms showed that the fish absorbed 35S-C12-LAS and 35S-C12-AS from the solutions principally through gills and that the surfactants absorbed were rapidly distributed throughout the body tissues and organs. High concentrations were found in gills, blood, hepatopancreas, kidney, and gall bladder. The elimination in the fish that were kept in clean fresh water after exposure were relatively rapid in most tissues and organs except for gall bladder. These results suggest that the surfactants absorbed in fish may have an adverse effect on many tissues and organs of fish. What influenced the distribution profile and concentration factors of the surfactants in tissues and organs of carp were the exposure time and the molecular structure of the surfactants.", "contents": "Uptake, distribution, and elimination of sodium linear alkylbenzene sulfonate and sodium alkyl sulfate in carp. Uptake, distribution, and elimination of labeled surfactants, 35S-labeled sodium laurylbenzenesulfonate (35S-C12-LAS) and 35S-labeled sodium lauryl sulfate (35S-C12-AS), were investigated in carp exposed to a low concentration level of the respective solutions found in river water in Japan by whole-body autoradiography and liquid scintillation counting. Whole-body autoradiograms showed that the fish absorbed 35S-C12-LAS and 35S-C12-AS from the solutions principally through gills and that the surfactants absorbed were rapidly distributed throughout the body tissues and organs. High concentrations were found in gills, blood, hepatopancreas, kidney, and gall bladder. The elimination in the fish that were kept in clean fresh water after exposure were relatively rapid in most tissues and organs except for gall bladder. These results suggest that the surfactants absorbed in fish may have an adverse effect on many tissues and organs of fish. What influenced the distribution profile and concentration factors of the surfactants in tissues and organs of carp were the exposure time and the molecular structure of the surfactants."}
{"id": "PMID:215399", "title": "[Effect of ionizing radiation on cerebral phosphodiesterase].", "content": "The authors examined the influence of x-ray irradiation on phosphodiesterase system in the brain of rats and the sensitivity of the enzyme to inhibitors (caffeine, theophyline, thyopental) and activators (imidozol). The animals (Wistar with weights of 150--200 gm/were irradiated singly with a dose of 737 r. Phosphodiesterase activity (PD) was determined by the method of Filburn and Carn (1972) at two substrate concentrations (1 and 100 microM). X-ray irradiation did not change PD with high Km, while the enzyme with low Km was reduced significantly and transitionaly. Caffeine, theophyline and thyopental inhibited more PD with low Km in the irradiated rats in comparison with the control nonirradiated rats. The activating effect of imidazol on PD with low Km was more marked in irradiated rats. These data could be interpreted in the light of the molecular mechanisms, determining the altered action of some drugs after x-ray irradiation.", "contents": "[Effect of ionizing radiation on cerebral phosphodiesterase]. The authors examined the influence of x-ray irradiation on phosphodiesterase system in the brain of rats and the sensitivity of the enzyme to inhibitors (caffeine, theophyline, thyopental) and activators (imidozol). The animals (Wistar with weights of 150--200 gm/were irradiated singly with a dose of 737 r. Phosphodiesterase activity (PD) was determined by the method of Filburn and Carn (1972) at two substrate concentrations (1 and 100 microM). X-ray irradiation did not change PD with high Km, while the enzyme with low Km was reduced significantly and transitionaly. Caffeine, theophyline and thyopental inhibited more PD with low Km in the irradiated rats in comparison with the control nonirradiated rats. The activating effect of imidazol on PD with low Km was more marked in irradiated rats. These data could be interpreted in the light of the molecular mechanisms, determining the altered action of some drugs after x-ray irradiation."}
{"id": "PMID:215396", "title": "Decreased serum cholesterol-binding reserve in diabetes mellitus.", "content": "Serum cholesterol-binding reserve (SCBR), the capacity of a serum sample to solubilize additional cholesterol in excess of its cholesterol content, was measured in 43 white male patients with maturity-onset diabetes in the age range of 35--59 years who were under treatment with insulin. The values were compared with those of 194 nondiabetic controls of the same race, sex, and age range. The mean +/- S.D. of SCBR of patients (71.9 +/- 29.3 mg./dl.) was lower than that of controls (88.9 +/- 30.9 mg./dl.) (p less than 0.001). Age in the range of 35 to 59 years had no correlation with SCBR in either patients or controls. SCBR was positively correlated with serum levels of cholesterol (SC) and triglycerides (TG) in both patients and controls. After adjustment for SC and TG, the difference in SCBR between patients and controls persisted (p less than 0.001). In 15 of 20 (75 per cent) patient-control pairs matched for SC and TG to within 5 per cent, the patient had lower SCBR (paired t-test, p less than 0.002). In 16 patients without elevation of serum lipid levels (SC below 250 and TG below 150 mg./dl.), the mean +/- S.D. of SCBR (59.1 +/- 17.7 mg./dl.) was lower than that of 49 controls having serum lipids in the same range (77.4 +/- 31.7 mg./dl.) (p less than 0.03). These results indicate an association of decreased SCBR with diabetes and are consistent with the hypothesis that low SCBR is associated with accelerated atherosclerosis and enhanced risk for coronary heart disease.", "contents": "Decreased serum cholesterol-binding reserve in diabetes mellitus. Serum cholesterol-binding reserve (SCBR), the capacity of a serum sample to solubilize additional cholesterol in excess of its cholesterol content, was measured in 43 white male patients with maturity-onset diabetes in the age range of 35--59 years who were under treatment with insulin. The values were compared with those of 194 nondiabetic controls of the same race, sex, and age range. The mean +/- S.D. of SCBR of patients (71.9 +/- 29.3 mg./dl.) was lower than that of controls (88.9 +/- 30.9 mg./dl.) (p less than 0.001). Age in the range of 35 to 59 years had no correlation with SCBR in either patients or controls. SCBR was positively correlated with serum levels of cholesterol (SC) and triglycerides (TG) in both patients and controls. After adjustment for SC and TG, the difference in SCBR between patients and controls persisted (p less than 0.001). In 15 of 20 (75 per cent) patient-control pairs matched for SC and TG to within 5 per cent, the patient had lower SCBR (paired t-test, p less than 0.002). In 16 patients without elevation of serum lipid levels (SC below 250 and TG below 150 mg./dl.), the mean +/- S.D. of SCBR (59.1 +/- 17.7 mg./dl.) was lower than that of 49 controls having serum lipids in the same range (77.4 +/- 31.7 mg./dl.) (p less than 0.03). These results indicate an association of decreased SCBR with diabetes and are consistent with the hypothesis that low SCBR is associated with accelerated atherosclerosis and enhanced risk for coronary heart disease."}
{"id": "PMID:215400", "title": "Nucleoside triphosphatase from the hen's egg white and vitelline membrane: purification, properties and relation to similar enzymes from the oviduct.", "content": "Hen's egg white and vitelline membrane nucleoside triphosphatases were purified resulting in active soluble subunits with MR 260,000 +/- 10,000. PH optima are divalent cation dependent and situated at pH 6.2 and 8.0 with ATP and at pH 6.15 with ADP as substrate. Ca2+ and Mg2+ are activators. Km and Ki values for Pi and PPi were determined. The enzymes are specific neither for ATP nor for ADP alone. No separation between nucleoside triphosphatase and nucleoside diphosphatase could be achieved. Differences found in their action can be due to differences in organization and properties of the (intermediary) enzyme-substrate complexes. A close relationship exists with homologous enzymes found in oviductal secretory cells and in oviductal secretions.", "contents": "Nucleoside triphosphatase from the hen's egg white and vitelline membrane: purification, properties and relation to similar enzymes from the oviduct. Hen's egg white and vitelline membrane nucleoside triphosphatases were purified resulting in active soluble subunits with MR 260,000 +/- 10,000. PH optima are divalent cation dependent and situated at pH 6.2 and 8.0 with ATP and at pH 6.15 with ADP as substrate. Ca2+ and Mg2+ are activators. Km and Ki values for Pi and PPi were determined. The enzymes are specific neither for ATP nor for ADP alone. No separation between nucleoside triphosphatase and nucleoside diphosphatase could be achieved. Differences found in their action can be due to differences in organization and properties of the (intermediary) enzyme-substrate complexes. A close relationship exists with homologous enzymes found in oviductal secretory cells and in oviductal secretions."}
{"id": "PMID:215402", "title": "Nucleotide sequence of the simian virus 40 Hind II + III restriction fragment J and the total amino acid sequence of the major structural protein VP1.", "content": "The HindII + III restriction fragment J (Hind-J) represents 4.58% of the simian virus 40 genome. The information present in Hind-J is expressed as part of the major, late 16-S messenger RNA, which codes for the structural protein VP1. The nucleotide sequence of the 240-base-pairs-long Hind fragment J has been determined by analysis of each oligonucleotide from both strands resulting from T1 or pancreatic RNase digestion of RNA transcribed from the DNA and from RNase digestion of ribo-substituted DNA. Large oligonucleotide blocks which could be constructed mainly on the basis of complementarity were subsequently ordered by partial chemical degradation of terminally labeled DNA. This direct DNA sequencing approach also completely confirmed the results obtained by both aforementioned RNase degradation methods. In the strand with the same polarity as the late mRNA, triplets corresponding to termination codons are present in two of the three reading frames. The one open reading frame connects in phase with the open reading frame of the neighboring HindII/ III fragments K, F and G, which have been published previously and which together with Hind-J span the total VP1 gene. Some features of the primary nucleotide sequence of this VP1 gene and the derived VP1 amino acid sequence are discussed.", "contents": "Nucleotide sequence of the simian virus 40 Hind II + III restriction fragment J and the total amino acid sequence of the major structural protein VP1. The HindII + III restriction fragment J (Hind-J) represents 4.58% of the simian virus 40 genome. The information present in Hind-J is expressed as part of the major, late 16-S messenger RNA, which codes for the structural protein VP1. The nucleotide sequence of the 240-base-pairs-long Hind fragment J has been determined by analysis of each oligonucleotide from both strands resulting from T1 or pancreatic RNase digestion of RNA transcribed from the DNA and from RNase digestion of ribo-substituted DNA. Large oligonucleotide blocks which could be constructed mainly on the basis of complementarity were subsequently ordered by partial chemical degradation of terminally labeled DNA. This direct DNA sequencing approach also completely confirmed the results obtained by both aforementioned RNase degradation methods. In the strand with the same polarity as the late mRNA, triplets corresponding to termination codons are present in two of the three reading frames. The one open reading frame connects in phase with the open reading frame of the neighboring HindII/ III fragments K, F and G, which have been published previously and which together with Hind-J span the total VP1 gene. Some features of the primary nucleotide sequence of this VP1 gene and the derived VP1 amino acid sequence are discussed."}
{"id": "PMID:215405", "title": "Biogenesis of cytochrome c in Neurospora crassa. Synthesis of apocytochrome c, transfer to mitochondria and conversion to Holocytochrome c.", "content": "1. Precipitating antibodies specific for apocytochrome c and holocytochrome c, respectively, were employed to study synthesis and intracellular transport of cytochrome c in Neurospora in vitro. 2. Apocytochrome c as well as holocytochrome c were found to be synthesized in a cell-free homogenate. A precursor product relationship between the two components is suggested by kinetic experiments. 3. Apocytochrome c synthesized in vitro was found in the post-ribosomal fraction and not in the mitochondrial fraction, whereas holocytochrome c synthesized in vitro was mainly detected in the mitochondrial fraction. A precursor product relationship between postribosomal apocytochrome c and mitochondrial holocytochrome c is indicated by the labelling data. In the microsomal fraction both apocytochrome c and holocytochrome c were found in low amounts. Their labeling kinetics do not subbest a precursor role of microsomal apocytochrome c or holocytochrome c. 4. Formation of holocytochrome c from apocytochrome c was observed when postribosomal supernatant containing apocytochrome c synthesized in vitro was incubated with isolated mitochondria, but not when incubated in the absence of mitochondria. The cytochrome c formed under these conditions was detected in the mitochondria. 5. Conversion of labelled apocytochrome c synthesized in vitro to holocytochrome c during incubation of a postribosomal supernatant with isolated mitochondria was inhibited when excess isolated apocytochrome c, but not when holocytochrome c was added. 6. The data presented are interpreted to show that apocytochrome c is synthesized on cytoplasmic ribosomes and released into the supernatant. It is suggested that apocytochrome c migrates to the inner mitochondrial membrane, where the heme group is covalently linked to the apoprotein. The hypothesis is put forward that the concomitant change in conformation leads to trapping of holocytochrome c in the membrane. The problems of permeability of the outer mitochondrial membrane to apocytochrome c and the site and nature of the reaction by which the heme group is linked to the apoprotein are discussed.", "contents": "Biogenesis of cytochrome c in Neurospora crassa. Synthesis of apocytochrome c, transfer to mitochondria and conversion to Holocytochrome c. 1. Precipitating antibodies specific for apocytochrome c and holocytochrome c, respectively, were employed to study synthesis and intracellular transport of cytochrome c in Neurospora in vitro. 2. Apocytochrome c as well as holocytochrome c were found to be synthesized in a cell-free homogenate. A precursor product relationship between the two components is suggested by kinetic experiments. 3. Apocytochrome c synthesized in vitro was found in the post-ribosomal fraction and not in the mitochondrial fraction, whereas holocytochrome c synthesized in vitro was mainly detected in the mitochondrial fraction. A precursor product relationship between postribosomal apocytochrome c and mitochondrial holocytochrome c is indicated by the labelling data. In the microsomal fraction both apocytochrome c and holocytochrome c were found in low amounts. Their labeling kinetics do not subbest a precursor role of microsomal apocytochrome c or holocytochrome c. 4. Formation of holocytochrome c from apocytochrome c was observed when postribosomal supernatant containing apocytochrome c synthesized in vitro was incubated with isolated mitochondria, but not when incubated in the absence of mitochondria. The cytochrome c formed under these conditions was detected in the mitochondria. 5. Conversion of labelled apocytochrome c synthesized in vitro to holocytochrome c during incubation of a postribosomal supernatant with isolated mitochondria was inhibited when excess isolated apocytochrome c, but not when holocytochrome c was added. 6. The data presented are interpreted to show that apocytochrome c is synthesized on cytoplasmic ribosomes and released into the supernatant. It is suggested that apocytochrome c migrates to the inner mitochondrial membrane, where the heme group is covalently linked to the apoprotein. The hypothesis is put forward that the concomitant change in conformation leads to trapping of holocytochrome c in the membrane. The problems of permeability of the outer mitochondrial membrane to apocytochrome c and the site and nature of the reaction by which the heme group is linked to the apoprotein are discussed."}
{"id": "PMID:215406", "title": "Native and latent forms of liver phosphorylase phosphatase. The non-identity of native phosphorylase phosphatase and synthase phosphatase.", "content": "The directly measurable (native) phosphorylase phosphatase present in a fresh mouse liver extract is bound to particulate glycogen and is not inhibited by heat-stable inhibitors. Treatment of the extract with trypsin or ethanol at room temperature caused a more than 10-fold increase in phosphorylase phosphatase activity. This increased activity stems from the activation of completely inactive (latent) enzyme, the major part of which is present in the high-speed supernatant. The trypsin-revealed activity can be completely blocked by heat-stable inhibitors. Treatment of the animal with glucocorticoids increases, and fasting decreases the activity of the native phosphorylase phosphatase. The level of latent enzyme, however, is unaffected by these treatments. The major portion of synthase phosphatase in the fresh liver extract is bound to glycogen. This enzyme is inhibited by the heat-stable inhibitor-2 and inactivated by trypsin or ethanol as well as by several treatments that have little effect on phosphorylase phosphatase. Upon DEAE-cellulose chromatography at 0 degrees C of a fresh liver extract, phosphorylase phosphatase and synthase phosphatase were resolved as separate, single peaks. If the preparation was not kept at 0 degrees C during the entire procedure, two peaks of each enzyme were observed. Under these conditions the first peak of phosphorylase phosphatase and of synthase phosphatase coincided. From these findings it is concluded that synthase phosphatase and phosphorylase phosphatase, in their native form, are distinct enzymes.", "contents": "Native and latent forms of liver phosphorylase phosphatase. The non-identity of native phosphorylase phosphatase and synthase phosphatase. The directly measurable (native) phosphorylase phosphatase present in a fresh mouse liver extract is bound to particulate glycogen and is not inhibited by heat-stable inhibitors. Treatment of the extract with trypsin or ethanol at room temperature caused a more than 10-fold increase in phosphorylase phosphatase activity. This increased activity stems from the activation of completely inactive (latent) enzyme, the major part of which is present in the high-speed supernatant. The trypsin-revealed activity can be completely blocked by heat-stable inhibitors. Treatment of the animal with glucocorticoids increases, and fasting decreases the activity of the native phosphorylase phosphatase. The level of latent enzyme, however, is unaffected by these treatments. The major portion of synthase phosphatase in the fresh liver extract is bound to glycogen. This enzyme is inhibited by the heat-stable inhibitor-2 and inactivated by trypsin or ethanol as well as by several treatments that have little effect on phosphorylase phosphatase. Upon DEAE-cellulose chromatography at 0 degrees C of a fresh liver extract, phosphorylase phosphatase and synthase phosphatase were resolved as separate, single peaks. If the preparation was not kept at 0 degrees C during the entire procedure, two peaks of each enzyme were observed. Under these conditions the first peak of phosphorylase phosphatase and of synthase phosphatase coincided. From these findings it is concluded that synthase phosphatase and phosphorylase phosphatase, in their native form, are distinct enzymes."}
{"id": "PMID:215408", "title": "A new method of chemical modification of N6-amino group in adenine nucleotides with formaldehyde and a thiol and its application to preparing immobilized ADP and ATP.", "content": "Reaction of AMP with formaldehyde and 3-mercaptopropionic acid at pH 11.7 gave a new AMP derivative, N6-[(2-carboxyethyl)thiomethyl]-AMP (I) in 91% yield and reaction at pH 3.1 gave another new derivative, N6,N6-bis[(2-carboxyethyl)thiomethyl]-AMP (II) in 57% yield. The structures were determined by their 13C and 1H nuclear magnetic resonance spectra coupled with those of the simple analogues, N6-[(2-carboxyethyl)thiomethyl]-9-methyladenine (III) and N6,N6-bis[(2-carboxyethyl)thiomethyl]-9-methyladenine (IV) which were synthesized from 9-methyladenine in the same way as for derivatives I and II. ADP and ATP were treated in the same way as AMP to afford the corresponding carboxyl derivatives, N6-[(2-carboxyethyl)thiomethyl]-ADP (V), N6-[(2-carboxyethyl)thiomethyl]-ATP (VI), N6,N6-bis[(2-carboxyethyl)thiomethyl]-ADP (X) and N6,N6-bis[(2-carboxyethyl)thiomethyl]-ATP (XI) in 71%, 75%, 53% and 40% yield, respectively. These compounds were coupled to 1,3-diaminopropane with a water-soluble carbodiimide to give the corresponding amino derivatives, N6-([N-3-aminopropyl)carbamoylethyl]thiomethyl)-ADP (VIII), N6-(N-(3-aminopropyl)carbamoylethyl]thiomethyl)-ATP (IX), N6,N6-bis([N-(3-aminopropyl)carbamoylethyl]thiomethyl)-ADP (XIII), and N6,N6-bis([N-(3-aminopropyl)carbamoylethyl]thiomethyl)-ATP (XIV), which were further bound to CNBr-activated dextran to give new polymer-bound derivatives of ADP and ATP. These free and bo-nd derivatives were tested for their coenzymic activities against several kinases. The activities of the ADP derivatives, V, VIII, X, XIII, dextran-bound VIII, and dextran-bound XIII against acetate kinase were 82%, 81%, 68%, 55%, 35%, and 15%, respectively, relative to ADP and those of the ATP derivatives, VI, IX, XI, XIV, dextran-bound IX, and dextran-bound XIV against hexokinase were 88%, 94%, 60%, 81%, 58%, and 49%, respectively, relative to ATP.", "contents": "A new method of chemical modification of N6-amino group in adenine nucleotides with formaldehyde and a thiol and its application to preparing immobilized ADP and ATP. Reaction of AMP with formaldehyde and 3-mercaptopropionic acid at pH 11.7 gave a new AMP derivative, N6-[(2-carboxyethyl)thiomethyl]-AMP (I) in 91% yield and reaction at pH 3.1 gave another new derivative, N6,N6-bis[(2-carboxyethyl)thiomethyl]-AMP (II) in 57% yield. The structures were determined by their 13C and 1H nuclear magnetic resonance spectra coupled with those of the simple analogues, N6-[(2-carboxyethyl)thiomethyl]-9-methyladenine (III) and N6,N6-bis[(2-carboxyethyl)thiomethyl]-9-methyladenine (IV) which were synthesized from 9-methyladenine in the same way as for derivatives I and II. ADP and ATP were treated in the same way as AMP to afford the corresponding carboxyl derivatives, N6-[(2-carboxyethyl)thiomethyl]-ADP (V), N6-[(2-carboxyethyl)thiomethyl]-ATP (VI), N6,N6-bis[(2-carboxyethyl)thiomethyl]-ADP (X) and N6,N6-bis[(2-carboxyethyl)thiomethyl]-ATP (XI) in 71%, 75%, 53% and 40% yield, respectively. These compounds were coupled to 1,3-diaminopropane with a water-soluble carbodiimide to give the corresponding amino derivatives, N6-([N-3-aminopropyl)carbamoylethyl]thiomethyl)-ADP (VIII), N6-(N-(3-aminopropyl)carbamoylethyl]thiomethyl)-ATP (IX), N6,N6-bis([N-(3-aminopropyl)carbamoylethyl]thiomethyl)-ADP (XIII), and N6,N6-bis([N-(3-aminopropyl)carbamoylethyl]thiomethyl)-ATP (XIV), which were further bound to CNBr-activated dextran to give new polymer-bound derivatives of ADP and ATP. These free and bo-nd derivatives were tested for their coenzymic activities against several kinases. The activities of the ADP derivatives, V, VIII, X, XIII, dextran-bound VIII, and dextran-bound XIII against acetate kinase were 82%, 81%, 68%, 55%, 35%, and 15%, respectively, relative to ADP and those of the ATP derivatives, VI, IX, XI, XIV, dextran-bound IX, and dextran-bound XIV against hexokinase were 88%, 94%, 60%, 81%, 58%, and 49%, respectively, relative to ATP."}
{"id": "PMID:215410", "title": "N-(2-Oxoacyl)amino acids and nitriles as final products of dipeptide chlorination mediated by the myeloperoxidase/H2O2/Cl- system.", "content": "The chlorination of dipeptides by the myeloperoxidase/H2O2/Cl- system takes place at the N-terminal amino group, whereas no chlorination of the amide nitrogen of the peptide bond can be observed. The N-terminal amino group is chlorinated to N-monochloroamine or/and N-dichloroamine. N-Monochloropeptides were the main products at higher pH values, at lower pH at mixture of N-monochloropeptides and N-dichloropeptides was formed owing to the dismutation of N-monochloroamine to N-dichloroamine. N-Monochloropeptides decompose, yielding NH3 and the corresponding N-(2-oxoacyl)amino acids. N-Dichlorodipeptides decompose faster but to nitriles and the free C-terminal amino acids. N-Dichloroglycyl-amino acid decomposes through a relatively stable intermediate (cyano-formylamino acid) to hydrogen cyanide, cyanogen chloride and the free C-terminal amino acid. Insulin chlorination also yields N-terminal glycyl and phenylalanyl N-monochloro derivatives, which deaminate to glyoxylyl and phenylpyruvyl residues.", "contents": "N-(2-Oxoacyl)amino acids and nitriles as final products of dipeptide chlorination mediated by the myeloperoxidase/H2O2/Cl- system. The chlorination of dipeptides by the myeloperoxidase/H2O2/Cl- system takes place at the N-terminal amino group, whereas no chlorination of the amide nitrogen of the peptide bond can be observed. The N-terminal amino group is chlorinated to N-monochloroamine or/and N-dichloroamine. N-Monochloropeptides were the main products at higher pH values, at lower pH at mixture of N-monochloropeptides and N-dichloropeptides was formed owing to the dismutation of N-monochloroamine to N-dichloroamine. N-Monochloropeptides decompose, yielding NH3 and the corresponding N-(2-oxoacyl)amino acids. N-Dichlorodipeptides decompose faster but to nitriles and the free C-terminal amino acids. N-Dichloroglycyl-amino acid decomposes through a relatively stable intermediate (cyano-formylamino acid) to hydrogen cyanide, cyanogen chloride and the free C-terminal amino acid. Insulin chlorination also yields N-terminal glycyl and phenylalanyl N-monochloro derivatives, which deaminate to glyoxylyl and phenylpyruvyl residues."}
{"id": "PMID:215412", "title": "Pre and post axial polysyndactyly, microcephaly and ptosis.", "content": "A five-year-old boy of Iranian origin with multiple anomalies is described. His parents are first and second cousins. He presented with short stature, psychomotor retardation, microcephaly, ptosis, dacryostenosis, partial left nerve deafness, high arched palate, bifid uvula, total fusion between incisors, asymmetric preaxial and postaxial polysyndactyly, brachyphalangy, kyphosis and spina bifida occulta of S1. To our knowledge, a similar case has not been reported previously.", "contents": "Pre and post axial polysyndactyly, microcephaly and ptosis. A five-year-old boy of Iranian origin with multiple anomalies is described. His parents are first and second cousins. He presented with short stature, psychomotor retardation, microcephaly, ptosis, dacryostenosis, partial left nerve deafness, high arched palate, bifid uvula, total fusion between incisors, asymmetric preaxial and postaxial polysyndactyly, brachyphalangy, kyphosis and spina bifida occulta of S1. To our knowledge, a similar case has not been reported previously."}
{"id": "PMID:215414", "title": "Facilitation of cardiac sympathetic function by angiotensin II: role of presynaptic angiotensin receptors.", "content": "Intravenous infusion of two separate doses of angiotensin II in pentobarbital-anesthetized, desipramine-treated animals produced dose-related increases in arterial blood pressure and caused significant potentiation of the cardioacceleration observed during the stimulation of the right postganglionic cardiac sympathetic nerve fibers. Positive chronotropic effects of intravenous norepinephrine were not altered during angiotensin II infusion. Prior administration of Saralasin, an angiotensin receptor antagonist, caused significant attenuation of the pressor action of angiotensin II, and also significantly antagonized the facilitatory effect of angiotensin II on sympathetic transmission to the myocardium. These results suggest that angiotensin II can cause facilitation of sympathetic nerve function to the myocardium via an action on angiotensin receptors which may be located on sympathetic nerve terminals.", "contents": "Facilitation of cardiac sympathetic function by angiotensin II: role of presynaptic angiotensin receptors. Intravenous infusion of two separate doses of angiotensin II in pentobarbital-anesthetized, desipramine-treated animals produced dose-related increases in arterial blood pressure and caused significant potentiation of the cardioacceleration observed during the stimulation of the right postganglionic cardiac sympathetic nerve fibers. Positive chronotropic effects of intravenous norepinephrine were not altered during angiotensin II infusion. Prior administration of Saralasin, an angiotensin receptor antagonist, caused significant attenuation of the pressor action of angiotensin II, and also significantly antagonized the facilitatory effect of angiotensin II on sympathetic transmission to the myocardium. These results suggest that angiotensin II can cause facilitation of sympathetic nerve function to the myocardium via an action on angiotensin receptors which may be located on sympathetic nerve terminals."}
{"id": "PMID:215415", "title": "Pharmacological actions of HS-6, an oxime, on the neuromuscular junction.", "content": "The effect of HS-6 [1-(2-hydroxyiminomethylpyridinium)-1-(3-carboxamidopyridinium)-dimethyl ether] on neuromuscular (NM) transmission was investigated using chick biventer cervicis (CBC), rat diaphragm (RD) and guinea pig ileum longitudinal muscle strip (GPLS) preparations. In the CBC preparation HS-6 did not cause a contraction, whereas it produced a dose-related contraction of the GPLS preparation. HS-6 produced a hemicholinium-like NM blockade in the CBC and RD preparations. This was supported by the fact that HS-6 inhibited choline uptake in erythrocytes. HS-6 inhibited the contractions of various nicotinic agonists in the CBC preparation and augmented the acetycholine contractions. The latter was due to AChE inhibition produced by HS-6.", "contents": "Pharmacological actions of HS-6, an oxime, on the neuromuscular junction. The effect of HS-6 [1-(2-hydroxyiminomethylpyridinium)-1-(3-carboxamidopyridinium)-dimethyl ether] on neuromuscular (NM) transmission was investigated using chick biventer cervicis (CBC), rat diaphragm (RD) and guinea pig ileum longitudinal muscle strip (GPLS) preparations. In the CBC preparation HS-6 did not cause a contraction, whereas it produced a dose-related contraction of the GPLS preparation. HS-6 produced a hemicholinium-like NM blockade in the CBC and RD preparations. This was supported by the fact that HS-6 inhibited choline uptake in erythrocytes. HS-6 inhibited the contractions of various nicotinic agonists in the CBC preparation and augmented the acetycholine contractions. The latter was due to AChE inhibition produced by HS-6."}
{"id": "PMID:215416", "title": "Modification by lidocaine of the discharges of primary endings of muscle spindles in cat tenuissimus muscle.", "content": "The effects of lidocaine (1--20 microgram/ml) on afferent discharge patterns of primary endings of muscle spindles in cat tenuissimus muscle were investigated. Discharge from the endings, recorded in Ia afferent axons, was evoked by ramp stretch of the muscle, stimulation of single static or dynamic fusimotor axons or by a combination of stretch and fusimotor stimulation. Spontaneous discharge of the endings at the initial length of the muscles was reduced by 2--5 microgram/ml and abolished by 10--15 microgram/ml lidocaine. The static but not the dynamic discharge elicited by muscle stretch was blocked by concentrations of 10--15 microgram/ml. The same concentrations abolished static and dynamic fusimotor influences on primary ending discharge. However, in one experiment where the spindle was microscopically observed, fusimotor stimulation still resulted in contraction of the intrafusal muscle even when fusimotor stimulation failed to elicit changes in discharge response patterns of the primary endings. These findings indicate that lidocaine interferes with the encoding mechanism prior to block of impulse conduction in either the fusimotor or afferent axons.", "contents": "Modification by lidocaine of the discharges of primary endings of muscle spindles in cat tenuissimus muscle. The effects of lidocaine (1--20 microgram/ml) on afferent discharge patterns of primary endings of muscle spindles in cat tenuissimus muscle were investigated. Discharge from the endings, recorded in Ia afferent axons, was evoked by ramp stretch of the muscle, stimulation of single static or dynamic fusimotor axons or by a combination of stretch and fusimotor stimulation. Spontaneous discharge of the endings at the initial length of the muscles was reduced by 2--5 microgram/ml and abolished by 10--15 microgram/ml lidocaine. The static but not the dynamic discharge elicited by muscle stretch was blocked by concentrations of 10--15 microgram/ml. The same concentrations abolished static and dynamic fusimotor influences on primary ending discharge. However, in one experiment where the spindle was microscopically observed, fusimotor stimulation still resulted in contraction of the intrafusal muscle even when fusimotor stimulation failed to elicit changes in discharge response patterns of the primary endings. These findings indicate that lidocaine interferes with the encoding mechanism prior to block of impulse conduction in either the fusimotor or afferent axons."}
{"id": "PMID:215418", "title": "Cardenolide analogs. An explanation for the usual properties of AY 22241.", "content": "AY 22241 (AY) was compared with digitoxigenin with respect to effects on myocardial contractility and inhibition of Na+, K+-ATPase. Ay was less potent than digitoxigenin but otherwise showed the same type of rapid onset and rapid reversal of activity usually associated with genins. Since AY is a glycoside, its behaviour was regarded as anomalous since glycosides usually show both slow onset and slow reversal of activity. Attempts were made to account for the genin-like properties of AY in terms of the model for the digitalis receptor proposed by Thomas et al. (1974a,b). It is suggested that the low potency and genin-like properties of AY may be due to the fact that the steroid is attached to the lactone through the carbon atom that is alpha to the carbonyl group. This feature could result in non-alignment of the sugar residue with the sugar binding site and might also reduce the effectiveness of the interaction of the steroid moiety with its binding site. A notable feature of AY toxicity was its extremely rapid progression to irreversible fibrillation.", "contents": "Cardenolide analogs. An explanation for the usual properties of AY 22241. AY 22241 (AY) was compared with digitoxigenin with respect to effects on myocardial contractility and inhibition of Na+, K+-ATPase. Ay was less potent than digitoxigenin but otherwise showed the same type of rapid onset and rapid reversal of activity usually associated with genins. Since AY is a glycoside, its behaviour was regarded as anomalous since glycosides usually show both slow onset and slow reversal of activity. Attempts were made to account for the genin-like properties of AY in terms of the model for the digitalis receptor proposed by Thomas et al. (1974a,b). It is suggested that the low potency and genin-like properties of AY may be due to the fact that the steroid is attached to the lactone through the carbon atom that is alpha to the carbonyl group. This feature could result in non-alignment of the sugar residue with the sugar binding site and might also reduce the effectiveness of the interaction of the steroid moiety with its binding site. A notable feature of AY toxicity was its extremely rapid progression to irreversible fibrillation."}
{"id": "PMID:215419", "title": "The role of beta-adrenoceptors in coronary blood flow distribution in normal and ischemic canine myocardium.", "content": "beta-Adrenoceptor agonists increase myocardial ischemic injury, mainly by elevating myocardial oxygen consumption. Moreover, it has been shown that isoprenaline may \"steal\" regional myocardial blood flow (RMBF) from ischemic to non ischemic areas and from epicardium to endocardium. The mechanisms of these two isoprenaline-induced redistributions of RMBF have been investigated by the use of radioactive microspheres in an experimental model of canine myocardial ischemia with simultaneous measurement of ST-segment elevation. Isoprenaline increased RMBF in both epi- and endocardial non ischemic areas and in epicardial ischemic areas, leading to a significant decrease in the endo/epi ratio. After atenolol, isoprenaline still increased RMBF but to a lesser extent and the endo/epi ratio was still decreased. Salbutamol, in doses inducing no significant changes in cardiac parameters or myocardial oxygen consumption, produced effects similar to those of isoprenaline. These results indicate a non-homogeneous beta2-stimulation-induced vasodilation in endo- and epicardium, which might be due either to the higher epicardial coronary vasocilatory reserve or to a heterogeneous distribution of transmural beta2-adrenoceptors. Isoprenaline also decreased the ischemic/non ischemic total blood flow ratio (I/NI) and caused further increases in ST-segment elevation. These effects were abolished by atenolol pretreatment, indicating the deleterious effects of isoprenaline-induced tachycardia in this I/NI decrease and in the ischemic injury.", "contents": "The role of beta-adrenoceptors in coronary blood flow distribution in normal and ischemic canine myocardium. beta-Adrenoceptor agonists increase myocardial ischemic injury, mainly by elevating myocardial oxygen consumption. Moreover, it has been shown that isoprenaline may \"steal\" regional myocardial blood flow (RMBF) from ischemic to non ischemic areas and from epicardium to endocardium. The mechanisms of these two isoprenaline-induced redistributions of RMBF have been investigated by the use of radioactive microspheres in an experimental model of canine myocardial ischemia with simultaneous measurement of ST-segment elevation. Isoprenaline increased RMBF in both epi- and endocardial non ischemic areas and in epicardial ischemic areas, leading to a significant decrease in the endo/epi ratio. After atenolol, isoprenaline still increased RMBF but to a lesser extent and the endo/epi ratio was still decreased. Salbutamol, in doses inducing no significant changes in cardiac parameters or myocardial oxygen consumption, produced effects similar to those of isoprenaline. These results indicate a non-homogeneous beta2-stimulation-induced vasodilation in endo- and epicardium, which might be due either to the higher epicardial coronary vasocilatory reserve or to a heterogeneous distribution of transmural beta2-adrenoceptors. Isoprenaline also decreased the ischemic/non ischemic total blood flow ratio (I/NI) and caused further increases in ST-segment elevation. These effects were abolished by atenolol pretreatment, indicating the deleterious effects of isoprenaline-induced tachycardia in this I/NI decrease and in the ischemic injury."}
{"id": "PMID:215428", "title": "Electrical coupling between primary afferents and amphibian motoneurons.", "content": "The short-latency DR-EPSPs resistant to Ca2+-lack and to addition of Mn2+ and Mg2+ result from electrical coupling between primary afferents and spinal motoneurons in frogs and toads. There are two time constants by which the time constant for the decay of the electronic DR-EPSP can be described: 1. the membrane time constant which determines the rate of passive decay of the membrane potential shift produced directly by the presynaptic spike, 2. the rate at which the presynaptic after-depolarization (ADP) declines.  The latter value is very large as compared with the postsynaptic membrane time constant. Presynaptic tetanization does not change the magnitude of the initial spike-induced component of the EPSP but its later slowly decaying portion is potentiated markedly as a result of the post-tetanic increase in the amplitude of the ADP. The perfusion with substances blocking potential dependent potassium channels (4-AP and TEA) greatly augments the DR-EPSP due to prolongation of the presynaptic spike and appearance of multiple discharges in the presynaptic fibers. An antidromic electrical coupling between motoneurons and the terminals of primary afferents was demonstrated in the isolated amphibian spinal cord perfused with zero Ca2+, 2 mM Mn2+ solution containing TEA or 4-AP. Under these conditions ventral root volleys may evoke local graded depolarizing potentials in some sensory fibers. Such antidromic coupling potentials can reach the critical level for generating a single or multiple discharge.", "contents": "Electrical coupling between primary afferents and amphibian motoneurons. The short-latency DR-EPSPs resistant to Ca2+-lack and to addition of Mn2+ and Mg2+ result from electrical coupling between primary afferents and spinal motoneurons in frogs and toads. There are two time constants by which the time constant for the decay of the electronic DR-EPSP can be described: 1. the membrane time constant which determines the rate of passive decay of the membrane potential shift produced directly by the presynaptic spike, 2. the rate at which the presynaptic after-depolarization (ADP) declines.  The latter value is very large as compared with the postsynaptic membrane time constant. Presynaptic tetanization does not change the magnitude of the initial spike-induced component of the EPSP but its later slowly decaying portion is potentiated markedly as a result of the post-tetanic increase in the amplitude of the ADP. The perfusion with substances blocking potential dependent potassium channels (4-AP and TEA) greatly augments the DR-EPSP due to prolongation of the presynaptic spike and appearance of multiple discharges in the presynaptic fibers. An antidromic electrical coupling between motoneurons and the terminals of primary afferents was demonstrated in the isolated amphibian spinal cord perfused with zero Ca2+, 2 mM Mn2+ solution containing TEA or 4-AP. Under these conditions ventral root volleys may evoke local graded depolarizing potentials in some sensory fibers. Such antidromic coupling potentials can reach the critical level for generating a single or multiple discharge."}
{"id": "PMID:215429", "title": "Two types of electronic EPSP evoked in amphibian motoneurons by ventral root stimulation.", "content": "Motoneurons of hemisected perfused frog spinal cord were used for intracellular recording of EPSP produced by ventral root stimulation. Two varieties of electrotonic VR-EPSP resistant to Ca-lack and to addition of 10 mM Mg2+ and 2 mM Mn2+ have been encountered. The early VR-EPSP started before the full somadendritic invasion and the time constant of their decay varied between 11 and 25 msec, mean 15.4 +/- 1.8 msec, i.e., it was significantly longer than the time constant of the motoneuronal membrane (2.6--6.9 msec, mean 4.4 +/- 0.5 msec). The late  VR-EPSPs appeared after a latent period which was significantly longer than that of an antidromic spike. They started after the full somadendritic invasion and had very rapid time course, the time constant of their decay approximated that of the motoneuronal membrane. The shape of the late VR-EPSP both before and after treatment with 4-AP of TEA which markedly facilitated its appearance resembled the shape of an antidromic spike, whereas this correlation was not found in the case of the early VR-EPSP. When the temperature was elevated above 18--19 degree C the late VR-EPSPs disappeared but the early VR-EPSPs still could be recorded. The available evidence suggests that the early VR-EPSPs are produced by direct synaptic interconnections between motoneurons and recurrent collaterals of the motor axons, and the VR-EPSPs are transmitted across dendrodendritic junctions.", "contents": "Two types of electronic EPSP evoked in amphibian motoneurons by ventral root stimulation. Motoneurons of hemisected perfused frog spinal cord were used for intracellular recording of EPSP produced by ventral root stimulation. Two varieties of electrotonic VR-EPSP resistant to Ca-lack and to addition of 10 mM Mg2+ and 2 mM Mn2+ have been encountered. The early VR-EPSP started before the full somadendritic invasion and the time constant of their decay varied between 11 and 25 msec, mean 15.4 +/- 1.8 msec, i.e., it was significantly longer than the time constant of the motoneuronal membrane (2.6--6.9 msec, mean 4.4 +/- 0.5 msec). The late  VR-EPSPs appeared after a latent period which was significantly longer than that of an antidromic spike. They started after the full somadendritic invasion and had very rapid time course, the time constant of their decay approximated that of the motoneuronal membrane. The shape of the late VR-EPSP both before and after treatment with 4-AP of TEA which markedly facilitated its appearance resembled the shape of an antidromic spike, whereas this correlation was not found in the case of the early VR-EPSP. When the temperature was elevated above 18--19 degree C the late VR-EPSPs disappeared but the early VR-EPSPs still could be recorded. The available evidence suggests that the early VR-EPSPs are produced by direct synaptic interconnections between motoneurons and recurrent collaterals of the motor axons, and the VR-EPSPs are transmitted across dendrodendritic junctions."}
{"id": "PMID:215430", "title": "Direct inhibitory synaptic linkage of pontomedullary reticular burst neurons with abducens motoneurons in the cat.", "content": "1. Unit spikes of burst neurons were extracellularly recorded in the pontomedullary reticular formation of the cat. These neurons were identified by their burst activity coincident with the quick inhibitory phase of the contralateral abducens nerve during vestibular nystagmus and their antidromic activation from the contralateral abducens nucleus. 2. When the extracellular field potentials in and near the abducens nucleus were triggered by spikes of a contralateral burs neuron, the averaged potential consisted of an early di- or triphasic spike and a late slow positive wave. The early spike was an action current caused by impulses conducting along the axon of the burst neuron. 3. The action potentials of a contralateral burst neuron. 3. The action potentials of a contralateral burst neuron were employed to trigger a post-spike average of the membrane potential of abducens motoneurons. Then unitary IPSPs with monosynaptic latencies were revealed. This provided direct evidence that the burst neurons are inhibitory in nature. The amplitudes of unitary IPSPs ranged from 18 to 220 mu V. Each inhibitory burst neuron branched widely in the abducens nucleus and was estimated to make inhibitory connections with approximately 60% of the motoneuron pool. 4. The post-spike average of compound potentials of the abducens nerve triggered by action potentials of contralateral single inhibitory burst neurons revealed inhibition of spike activity with latencies and time courses compatible with those of unitary IPSPs in motoneurons. The inhibition was observed with all inhibitory burst neurons tested.", "contents": "Direct inhibitory synaptic linkage of pontomedullary reticular burst neurons with abducens motoneurons in the cat. 1. Unit spikes of burst neurons were extracellularly recorded in the pontomedullary reticular formation of the cat. These neurons were identified by their burst activity coincident with the quick inhibitory phase of the contralateral abducens nerve during vestibular nystagmus and their antidromic activation from the contralateral abducens nucleus. 2. When the extracellular field potentials in and near the abducens nucleus were triggered by spikes of a contralateral burs neuron, the averaged potential consisted of an early di- or triphasic spike and a late slow positive wave. The early spike was an action current caused by impulses conducting along the axon of the burst neuron. 3. The action potentials of a contralateral burst neuron. 3. The action potentials of a contralateral burst neuron were employed to trigger a post-spike average of the membrane potential of abducens motoneurons. Then unitary IPSPs with monosynaptic latencies were revealed. This provided direct evidence that the burst neurons are inhibitory in nature. The amplitudes of unitary IPSPs ranged from 18 to 220 mu V. Each inhibitory burst neuron branched widely in the abducens nucleus and was estimated to make inhibitory connections with approximately 60% of the motoneuron pool. 4. The post-spike average of compound potentials of the abducens nerve triggered by action potentials of contralateral single inhibitory burst neurons revealed inhibition of spike activity with latencies and time courses compatible with those of unitary IPSPs in motoneurons. The inhibition was observed with all inhibitory burst neurons tested."}
{"id": "PMID:215431", "title": "Prominent excitatory pathways in the cat visual cortex (A 17 and A 18): a current source density analysis of electrically evoked potentials.", "content": "The current source density (CSD) method in its one-dimensional approximation is used to analyze the field potentials in visual areas 18 and 17 of the cat, which were elicited by stimulating electrodes in the optic chiasm (OX), the optic radiation (OR) or in the respective cortical area itself. The CSD analysis reveals the basic pattern of excitatory postsynaptic activity. 1. In both visual areas the basic specific excitatory activity flows along three different intracortical pathways, all starting in layer IV: The first pathway relays activity from layer IV to supragranular pyramidal cells via strong, local connections to layer III and from there through long-distance connections to layer II. The second pathway conveys activity from layer IV to layer V, where it mainly contacts apical dendrites of layer VI pyramidal cells. This infragranular polysynaptic activity is not clearly resolvable into separate components, suggesting that it is conveyed by various groups of axons, among them long-distance horizontal connections. The third pathway has one synaptic relay within layer IV and then conveys activity to layer III. In addition, monosynaptic activity is revealed in layers VI and I. 2. In A 18 one coherent, fast-conducting group of afferents induces this basic activity pattern. In A 17 no such fast conducting input is resolvable; the supragranular activity is induced by a small group of afferents with intermediate conduction velocity, which terminate in the upper part of layer IV. The infragranular activity is induced by afferents with slower and widely scattered conduction velocities, which terminate in the lower part of layer IV. The layer VI input is very prominent in A 17 and also has a wide latency scatter. 3. The supragranular activity is more prominent in A 18 than in A 17 and the respective layers appear thicker, in accordance with anatomy. In A 17 the infragranular activity prevails and layers IV and VI appear very broad, again in accordance with anatomy. 4. Comparison of the CSDs with the original evoked potentials shows that the surface evoked potentials over A 18 reflect the three dipolar sink/source distributions of the coherent monosynaptic activity in layer IV and of the two prominent polysynaptic activities in layers III and II. The widely scattered activity in the lower part of layer IV in A 17 and all infragranular activities in both areas generate smaller, partly closed-field potentials; those are not discernible from the strong far-field potentials which originate from the supragranular activity and--especially in A 17--from farther distant events.", "contents": "Prominent excitatory pathways in the cat visual cortex (A 17 and A 18): a current source density analysis of electrically evoked potentials. The current source density (CSD) method in its one-dimensional approximation is used to analyze the field potentials in visual areas 18 and 17 of the cat, which were elicited by stimulating electrodes in the optic chiasm (OX), the optic radiation (OR) or in the respective cortical area itself. The CSD analysis reveals the basic pattern of excitatory postsynaptic activity. 1. In both visual areas the basic specific excitatory activity flows along three different intracortical pathways, all starting in layer IV: The first pathway relays activity from layer IV to supragranular pyramidal cells via strong, local connections to layer III and from there through long-distance connections to layer II. The second pathway conveys activity from layer IV to layer V, where it mainly contacts apical dendrites of layer VI pyramidal cells. This infragranular polysynaptic activity is not clearly resolvable into separate components, suggesting that it is conveyed by various groups of axons, among them long-distance horizontal connections. The third pathway has one synaptic relay within layer IV and then conveys activity to layer III. In addition, monosynaptic activity is revealed in layers VI and I. 2. In A 18 one coherent, fast-conducting group of afferents induces this basic activity pattern. In A 17 no such fast conducting input is resolvable; the supragranular activity is induced by a small group of afferents with intermediate conduction velocity, which terminate in the upper part of layer IV. The infragranular activity is induced by afferents with slower and widely scattered conduction velocities, which terminate in the lower part of layer IV. The layer VI input is very prominent in A 17 and also has a wide latency scatter. 3. The supragranular activity is more prominent in A 18 than in A 17 and the respective layers appear thicker, in accordance with anatomy. In A 17 the infragranular activity prevails and layers IV and VI appear very broad, again in accordance with anatomy. 4. Comparison of the CSDs with the original evoked potentials shows that the surface evoked potentials over A 18 reflect the three dipolar sink/source distributions of the coherent monosynaptic activity in layer IV and of the two prominent polysynaptic activities in layers III and II. The widely scattered activity in the lower part of layer IV in A 17 and all infragranular activities in both areas generate smaller, partly closed-field potentials; those are not discernible from the strong far-field potentials which originate from the supragranular activity and--especially in A 17--from farther distant events."}
{"id": "PMID:215432", "title": "Afferent fibres from muscle receptors in the posterior nerve of the cat's knee joint.", "content": "The properties of some receptors with afferent fibres in the cat's posterior knee joint nerve have been examined, especially those discharging tonically with the joint in intermediate positions between full flexion and extension. Some of these receptors behave like muscle spindles, and respond to manoeuvres which stretch popliteus muscle. Both in single unit and whole nerve recordings their discharge pauses during a popliteus twitch, and can be strikingly augmented by tetanic stimulation of a number of popliteus fusimotor fibres isolated from ventral root filaments. The action of succinylcholine on these receptors closely resembles its effect on popliteus spindle units with fibres sited normally in the popliteus nerve. Other units with properties suggesting origin from popliteus tendon organs were also observed; their fibres and those of the spindle units conducted at Group I velocity. It is concluded that some afferent fibres from popliteus spindles and possibly tendon organs commonly pursue an aberrant course in the posterior articular nerve of the knee joint.", "contents": "Afferent fibres from muscle receptors in the posterior nerve of the cat's knee joint. The properties of some receptors with afferent fibres in the cat's posterior knee joint nerve have been examined, especially those discharging tonically with the joint in intermediate positions between full flexion and extension. Some of these receptors behave like muscle spindles, and respond to manoeuvres which stretch popliteus muscle. Both in single unit and whole nerve recordings their discharge pauses during a popliteus twitch, and can be strikingly augmented by tetanic stimulation of a number of popliteus fusimotor fibres isolated from ventral root filaments. The action of succinylcholine on these receptors closely resembles its effect on popliteus spindle units with fibres sited normally in the popliteus nerve. Other units with properties suggesting origin from popliteus tendon organs were also observed; their fibres and those of the spindle units conducted at Group I velocity. It is concluded that some afferent fibres from popliteus spindles and possibly tendon organs commonly pursue an aberrant course in the posterior articular nerve of the knee joint."}
{"id": "PMID:215433", "title": "Neuron-glia interactions: indirect effect of GABA on cultured glial cells.", "content": "A study was made of the action of GABA on the membrane potentail and resistance of satellite glial (SG) cells in cultures of rat dorsal root ganglia. GABA (10(-4) M) depolarized all SG cells tested without producing significant changes in membrane resistance. Similar results were obtained from astrocytes of cultured rat spinal cord and brain stem, although only half of the cells tested were depolarized by GABA. Bicuculline (10(-5) and 10(-6) M) which blocked the GABA-depolarization on cultured dorsal root ganglion (DRG) neurons, also markedly reduced or blocked the action of GABA on SG cells. When GABA was tested in sodium-free bathing solution, the amino acid caused a depolarization of similar shape and amplitude as in normal (137 mM Na+) bathing fluid, indicating that uptake processes are probably not involved in producing the depolarization by GABA. It is suggested that the depolarizing action of GABA on glial cells is an indirect effect due to the release of potassium from adjacent neurons during the action of the amino acid.", "contents": "Neuron-glia interactions: indirect effect of GABA on cultured glial cells. A study was made of the action of GABA on the membrane potentail and resistance of satellite glial (SG) cells in cultures of rat dorsal root ganglia. GABA (10(-4) M) depolarized all SG cells tested without producing significant changes in membrane resistance. Similar results were obtained from astrocytes of cultured rat spinal cord and brain stem, although only half of the cells tested were depolarized by GABA. Bicuculline (10(-5) and 10(-6) M) which blocked the GABA-depolarization on cultured dorsal root ganglion (DRG) neurons, also markedly reduced or blocked the action of GABA on SG cells. When GABA was tested in sodium-free bathing solution, the amino acid caused a depolarization of similar shape and amplitude as in normal (137 mM Na+) bathing fluid, indicating that uptake processes are probably not involved in producing the depolarization by GABA. It is suggested that the depolarizing action of GABA on glial cells is an indirect effect due to the release of potassium from adjacent neurons during the action of the amino acid."}
{"id": "PMID:215434", "title": "The mole of pallido-thalamic transmission investigated with intracellular recording from cat thalamus.", "content": "Pallido-thalamic transmission was studied by intracellular recording from neurons in the ventrolateral (VL) and ventroanterior (VA) nuclei of the thalamus in cats anesthetized with pentobarbital. Stimulation of the entopeduncular nucleus (ENT) produced short latency, inhibitory postsynaptic potentials in the VL-VA neurons (1.60 ms on average). When stimuli were applied closer to the VL-VA region along the pallido-thalamic pathway, i.e., to the rostral Forel's field, the IPSP latency was significantly reduced. Linear regression analysis of the IPSP latency against conduction distance between different stimulating the recording positions indicated that the IPSP was produced through a monosynaptic pathway at a conduction velocity of 5 to 11 m/s. The neurons which received IPSPs from the ENT distributed in the rostromedial VL and in the rostral VA, whereas relay cells responding only to the contralateral brachium conjunctivum were found in the caudal VL and in the dorsolateral portion of the rostral VL-VA complex. Reciprocal convergence of pallidal and cerebellar impulses were observed in only a small number of cells, which were located in the border between the two neuron groups. Recording of extracellular field potentials and focal stimulation within and around the rostral VL also indicated that the fiber potentials arose from the ENT nucleus and propagated along a bundle of fibers which terminated within the rostromedial VL-VA complex. These results are all explicable by assuming that the entopeduncular neurons are inhibitory in nature and so inhibit thalamic neurons monosynaptically.", "contents": "The mole of pallido-thalamic transmission investigated with intracellular recording from cat thalamus. Pallido-thalamic transmission was studied by intracellular recording from neurons in the ventrolateral (VL) and ventroanterior (VA) nuclei of the thalamus in cats anesthetized with pentobarbital. Stimulation of the entopeduncular nucleus (ENT) produced short latency, inhibitory postsynaptic potentials in the VL-VA neurons (1.60 ms on average). When stimuli were applied closer to the VL-VA region along the pallido-thalamic pathway, i.e., to the rostral Forel's field, the IPSP latency was significantly reduced. Linear regression analysis of the IPSP latency against conduction distance between different stimulating the recording positions indicated that the IPSP was produced through a monosynaptic pathway at a conduction velocity of 5 to 11 m/s. The neurons which received IPSPs from the ENT distributed in the rostromedial VL and in the rostral VA, whereas relay cells responding only to the contralateral brachium conjunctivum were found in the caudal VL and in the dorsolateral portion of the rostral VL-VA complex. Reciprocal convergence of pallidal and cerebellar impulses were observed in only a small number of cells, which were located in the border between the two neuron groups. Recording of extracellular field potentials and focal stimulation within and around the rostral VL also indicated that the fiber potentials arose from the ENT nucleus and propagated along a bundle of fibers which terminated within the rostromedial VL-VA complex. These results are all explicable by assuming that the entopeduncular neurons are inhibitory in nature and so inhibit thalamic neurons monosynaptically."}
{"id": "PMID:215435", "title": "The ventral spino-olivocerebellar system in the cat. V. Supraspinal control of spinal transmission.", "content": "1. The transmission from the flexor reflex afferents (FRA) and from tracts running in the ipsilateral half of the spinal cord to the spino-olivocerebellar paths ascending through the ventral funiculus (VF-SOCPs; Oscarsson and Sj\u00f6lund, 1977) was compared with the transmission from these sources to segmental reflex arcs. The climbing fibre responses evoked in Purkinje cells by electrical stimulation of limb nerves and spinal tracts were monitored by recording the mass activity at the cerebellar surface simultaneously from several termination zones, while the activity in flexor motoneurones was recorded from a flexor nerve and the primary afferent depolarization from a dorsal filament. 2. Changes in the segmental reflex response were produced by release from the tonic inhibition of transmission from the FRA in decerebrate preparations and by conditioning electrical stimulation of dissected spinal funiculi containing inhibitory descending tracts. 3. The changes of the transmission from the FRA to two of the paths, the a- and b2-VF-SOCPs, parallelled the changes of the transmission to the segmental reflex arcs. On the other hand, the monosynaptic transmission from the FRA to the c1- and c3-VF-SOCPs was not significantly influenced by the inhibitory descending control systems. 4. The a- and b2-VF-SOCPs but not the c1- and c3-VF-SOCPs received polysynaptic excitation from tracts running in the ipsilateral half of the spinal cord. 5. The suggestion that the a- and b2-VF-SOCPs carry information related to interneuronal activity in segmental centres, whereas the c1- and c3-VF-SOCPs forward information mainly related to peripheral events (Andersson and Sj\u00f6lund, 1978) is supported by the present findings.", "contents": "The ventral spino-olivocerebellar system in the cat. V. Supraspinal control of spinal transmission. 1. The transmission from the flexor reflex afferents (FRA) and from tracts running in the ipsilateral half of the spinal cord to the spino-olivocerebellar paths ascending through the ventral funiculus (VF-SOCPs; Oscarsson and Sj\u00f6lund, 1977) was compared with the transmission from these sources to segmental reflex arcs. The climbing fibre responses evoked in Purkinje cells by electrical stimulation of limb nerves and spinal tracts were monitored by recording the mass activity at the cerebellar surface simultaneously from several termination zones, while the activity in flexor motoneurones was recorded from a flexor nerve and the primary afferent depolarization from a dorsal filament. 2. Changes in the segmental reflex response were produced by release from the tonic inhibition of transmission from the FRA in decerebrate preparations and by conditioning electrical stimulation of dissected spinal funiculi containing inhibitory descending tracts. 3. The changes of the transmission from the FRA to two of the paths, the a- and b2-VF-SOCPs, parallelled the changes of the transmission to the segmental reflex arcs. On the other hand, the monosynaptic transmission from the FRA to the c1- and c3-VF-SOCPs was not significantly influenced by the inhibitory descending control systems. 4. The a- and b2-VF-SOCPs but not the c1- and c3-VF-SOCPs received polysynaptic excitation from tracts running in the ipsilateral half of the spinal cord. 5. The suggestion that the a- and b2-VF-SOCPs carry information related to interneuronal activity in segmental centres, whereas the c1- and c3-VF-SOCPs forward information mainly related to peripheral events (Andersson and Sj\u00f6lund, 1978) is supported by the present findings."}
{"id": "PMID:215436", "title": "Polysynaptic activation of the dentate gyrus of the hippocampal formation: an olfactory input via the lateral entorhinal cortex.", "content": "The possibility that olfactory input is transmitted to specific subregions of the hippocampal formation via the entorhinal cortex was investigated electrophysiologically by analyzing the laminar profiles of potentials evoked in the hippocampal formation by stimulation of the lateral olfactory tract (LOT). LOT stimulation resulted in long latency (14--20 ms) evoked responses in the dentate gyrus of the hippocampal formation ipsilateral to the stimulation. The variable long latency of these responses and their inability to follow stimulus rates of 40/s suggested that these potentials reflected polysynaptic activation. Analysis of the laminar profiles of the evoked potentials indicated that the responses originated from a synaptic field localized in the outer portion of the stratum moleculare of the dentate gyrus, a terminal distribution which overlaps that of the lateral entorhinal cortical (LEC) projection to the dentate gyrus. Lesions of the LEC eliminated the long latency responses in the dentate gyrus evoked by LOT stimulation. In addition, a conditioning pulse delivered either to the LOT or to the LEC produced paired pulse potentiation of the response elicited by subsequent stimulation of the other structure. No evidence was found to indicate that responses were generated in regio superior of the hippocampus proper following LOT stimulation. Taken together, these results suggest that stimulation of the LOT activates the dentate gyrus of the hippocampal formation by multisynaptic pathways which relay through the lateral portion of the entorhinal area. This finding is discussed with regard to entorhinal cortical organization and the known olfactory projections to the LEC.", "contents": "Polysynaptic activation of the dentate gyrus of the hippocampal formation: an olfactory input via the lateral entorhinal cortex. The possibility that olfactory input is transmitted to specific subregions of the hippocampal formation via the entorhinal cortex was investigated electrophysiologically by analyzing the laminar profiles of potentials evoked in the hippocampal formation by stimulation of the lateral olfactory tract (LOT). LOT stimulation resulted in long latency (14--20 ms) evoked responses in the dentate gyrus of the hippocampal formation ipsilateral to the stimulation. The variable long latency of these responses and their inability to follow stimulus rates of 40/s suggested that these potentials reflected polysynaptic activation. Analysis of the laminar profiles of the evoked potentials indicated that the responses originated from a synaptic field localized in the outer portion of the stratum moleculare of the dentate gyrus, a terminal distribution which overlaps that of the lateral entorhinal cortical (LEC) projection to the dentate gyrus. Lesions of the LEC eliminated the long latency responses in the dentate gyrus evoked by LOT stimulation. In addition, a conditioning pulse delivered either to the LOT or to the LEC produced paired pulse potentiation of the response elicited by subsequent stimulation of the other structure. No evidence was found to indicate that responses were generated in regio superior of the hippocampus proper following LOT stimulation. Taken together, these results suggest that stimulation of the LOT activates the dentate gyrus of the hippocampal formation by multisynaptic pathways which relay through the lateral portion of the entorhinal area. This finding is discussed with regard to entorhinal cortical organization and the known olfactory projections to the LEC."}
{"id": "PMID:215437", "title": "Direct excitation of neck motoneurons by interstitiospinal fibers.", "content": "1. Responses of neck motoneurons to stimulation of the interstitial nucleus of cajal (INC) were recorded intracellularly in cats under chloralose anesthesia. When stimuli were applied within or close to the INC, short latency, monosynaptic excitatory postsynaptic potentials (EPSPs) were evoked in many neck motoneurons. Such EPSPs were not evoked by stimulating mesencephalic regions outside the INC. 2. Stimulation of the ipsilateral INC produced monosynaptic EPSPs consistently in biventer cervicis-complexus (BCC) motoneurons, while such EPSPs were observed in about two thirds of the splenius (SP) motoneurons and half of the trapezius (TR) motoneurons tested. Stimulation of the contralateral INC produced weak monosynaptic EPSPs in about half the BCC motoneurons and in a few SP and TR motoneurons. All types of motoneurons also received longer latency, apparently polysynaptic, PSPs from both INCs. In BCC and TR motoneurons these were mainly EPSPs, in SP, mixed excitatory and inhibitory PSPs. 3. Monosynaptic EPSPs evoked by INC stimulation were not eliminated by acute and chronic parasagittal and transverse lesions placed to interrupt the bifurcating axons of all vestibulospinal and many reticulospinal neurons. No significant collision was observed between EPSPs evoked by INC and vestibular or reticular stimulation. The EPSPs evoked by stimulation of the INC therefore appear to have been produced by activation of interstitiospinal neurons rather than by an axon reflex mechanism. 4. The properties of a number of interstitiospinal neurons were observed while recording extracellularly from the mesencephalon to map the location of the INC. One third of the interstitiospinal neurons activated antidromically from the C4  segment could also be activated antidromically from L1. These lumbar-projecting neurons had conduction velocities ranging from 15--123 m/s. Several interstitiospinal neurons sending axons to the ventral horn of the neck segments were identified and two of these were found to be branching neurons that projected both to the neck and to lower levels of the spinal cord.", "contents": "Direct excitation of neck motoneurons by interstitiospinal fibers. 1. Responses of neck motoneurons to stimulation of the interstitial nucleus of cajal (INC) were recorded intracellularly in cats under chloralose anesthesia. When stimuli were applied within or close to the INC, short latency, monosynaptic excitatory postsynaptic potentials (EPSPs) were evoked in many neck motoneurons. Such EPSPs were not evoked by stimulating mesencephalic regions outside the INC. 2. Stimulation of the ipsilateral INC produced monosynaptic EPSPs consistently in biventer cervicis-complexus (BCC) motoneurons, while such EPSPs were observed in about two thirds of the splenius (SP) motoneurons and half of the trapezius (TR) motoneurons tested. Stimulation of the contralateral INC produced weak monosynaptic EPSPs in about half the BCC motoneurons and in a few SP and TR motoneurons. All types of motoneurons also received longer latency, apparently polysynaptic, PSPs from both INCs. In BCC and TR motoneurons these were mainly EPSPs, in SP, mixed excitatory and inhibitory PSPs. 3. Monosynaptic EPSPs evoked by INC stimulation were not eliminated by acute and chronic parasagittal and transverse lesions placed to interrupt the bifurcating axons of all vestibulospinal and many reticulospinal neurons. No significant collision was observed between EPSPs evoked by INC and vestibular or reticular stimulation. The EPSPs evoked by stimulation of the INC therefore appear to have been produced by activation of interstitiospinal neurons rather than by an axon reflex mechanism. 4. The properties of a number of interstitiospinal neurons were observed while recording extracellularly from the mesencephalon to map the location of the INC. One third of the interstitiospinal neurons activated antidromically from the C4  segment could also be activated antidromically from L1. These lumbar-projecting neurons had conduction velocities ranging from 15--123 m/s. Several interstitiospinal neurons sending axons to the ventral horn of the neck segments were identified and two of these were found to be branching neurons that projected both to the neck and to lower levels of the spinal cord."}
{"id": "PMID:215438", "title": "Effects of exogenous neuraminidase on unit activity in frog spinal cord and fish optic tectum.", "content": "The effect of exogenous neuraminidase on spontaneous and evoked synaptic activity was investigated following injection of the enzyme into frog spinal cord and into cord and into the carp optic tectum. 1. Injection of enzyme into spinal cord segments caused a significant increase of motoneuron activity in the corresponding spinal nerve, which lasted for 7--31 min. 2. The amplitude of postsynaptic evoked potentials in the optic tectum was increased after neuraminidase injection up to 200% of control level for 20--40 min, whereas the amplitude of summed action potentials of retino-tectal afferents remained unchanged. 3. Similar effects were observed in single cell responses of the optic tectum with some differences in the degree of increase in activity, as well as latency and final depression of the stimulus response. 4. The extent of neuraminic acid liberation following neuraminidase treatment was determined biochemically. In both tissues investigated the amount of free neuraminic acid was increased significantly (4--5.5 fold) after enzyme treatment. Whereas after enzyme injection into spinal cord and optic tectum the percentage release of total glycoprotein- and glycolipidbound neuraminic acid was 12% and 15%, respectively, liberation from enzyme incubated tissue homogenates was somewhat higher (20.5% and 24%).", "contents": "Effects of exogenous neuraminidase on unit activity in frog spinal cord and fish optic tectum. The effect of exogenous neuraminidase on spontaneous and evoked synaptic activity was investigated following injection of the enzyme into frog spinal cord and into cord and into the carp optic tectum. 1. Injection of enzyme into spinal cord segments caused a significant increase of motoneuron activity in the corresponding spinal nerve, which lasted for 7--31 min. 2. The amplitude of postsynaptic evoked potentials in the optic tectum was increased after neuraminidase injection up to 200% of control level for 20--40 min, whereas the amplitude of summed action potentials of retino-tectal afferents remained unchanged. 3. Similar effects were observed in single cell responses of the optic tectum with some differences in the degree of increase in activity, as well as latency and final depression of the stimulus response. 4. The extent of neuraminic acid liberation following neuraminidase treatment was determined biochemically. In both tissues investigated the amount of free neuraminic acid was increased significantly (4--5.5 fold) after enzyme treatment. Whereas after enzyme injection into spinal cord and optic tectum the percentage release of total glycoprotein- and glycolipidbound neuraminic acid was 12% and 15%, respectively, liberation from enzyme incubated tissue homogenates was somewhat higher (20.5% and 24%)."}
{"id": "PMID:215444", "title": "Mass fragmentographic determination of cholecalciferol and 25-hydroxycholecalciferol in human serum.", "content": "The serum extracts were purified by column-, thin layer- and high pressure liquid chromatography. Deuterated cholecalciferol and deuterated 25-hydroxycholecalciferol were used in internal standards. The quantitative analysis was performed using GC-mass fragmentography technique of TMS-ethers.", "contents": "Mass fragmentographic determination of cholecalciferol and 25-hydroxycholecalciferol in human serum. The serum extracts were purified by column-, thin layer- and high pressure liquid chromatography. Deuterated cholecalciferol and deuterated 25-hydroxycholecalciferol were used in internal standards. The quantitative analysis was performed using GC-mass fragmentography technique of TMS-ethers."}
{"id": "PMID:215445", "title": "Imbalance in the activities of alkaline phosphatase and Na+-K+-ATPase in the brain of experimentally induced phenylketonuric squirrels (Funambulus palmarum).", "content": "Phenylketonuric squirrels have shown marked inhibition of alkaline phosphatase in the olfactory lobes and cerebral hemispheres, whereas the Na+-K+-ATPase remained less altered. In the pathogenesis of phenylketonuria inhibition of alkaline phosphatase at the level of \"Blood-Brain Barrier\" (BBB), leads transport system to impaired functioning.", "contents": "Imbalance in the activities of alkaline phosphatase and Na+-K+-ATPase in the brain of experimentally induced phenylketonuric squirrels (Funambulus palmarum). Phenylketonuric squirrels have shown marked inhibition of alkaline phosphatase in the olfactory lobes and cerebral hemispheres, whereas the Na+-K+-ATPase remained less altered. In the pathogenesis of phenylketonuria inhibition of alkaline phosphatase at the level of \"Blood-Brain Barrier\" (BBB), leads transport system to impaired functioning."}
{"id": "PMID:215446", "title": "Trichinella spiralis: acceleration and inhibition of cyst calcification in rats.", "content": "Daily administration of vitamin D3 (75,000 IU/kg b. wt) for 7 days accelerated Trichinella spiralis cyst calcification in rats with a 14-week-old infection. When disodium ethane-1-hydroxy-1, 1-diphosphonate (EHDP) was administered (50 mg/kg b. wt) from 2 days before until 2 days after vitamin D3 treatment, cyst calcification was inhibited. Thus, the ability to inhibit E. spiralis calcification has demonstrated for the first time.", "contents": "Trichinella spiralis: acceleration and inhibition of cyst calcification in rats. Daily administration of vitamin D3 (75,000 IU/kg b. wt) for 7 days accelerated Trichinella spiralis cyst calcification in rats with a 14-week-old infection. When disodium ethane-1-hydroxy-1, 1-diphosphonate (EHDP) was administered (50 mg/kg b. wt) from 2 days before until 2 days after vitamin D3 treatment, cyst calcification was inhibited. Thus, the ability to inhibit E. spiralis calcification has demonstrated for the first time."}
{"id": "PMID:215447", "title": "Effect of sodium butyrate in combination with prostaglandin E1 and inhibitors of cyclic nucleotide phosphodiesterase on human amelanotic melanoma cells in culture.", "content": "Sodium butyrate and cyclic AMP-stimulating agents (prostaglandin E1, papaverine, theophylline, and RO20-1724) caused reductions in the cell number (primarily due to reduction in cell division) when added individually to human melanoma cells in culture. However, the combination of sodium butyrate with one of the cyclic AMP-stimulating agents produced a marked reduction in cell number (primarily due to cell death).", "contents": "Effect of sodium butyrate in combination with prostaglandin E1 and inhibitors of cyclic nucleotide phosphodiesterase on human amelanotic melanoma cells in culture. Sodium butyrate and cyclic AMP-stimulating agents (prostaglandin E1, papaverine, theophylline, and RO20-1724) caused reductions in the cell number (primarily due to reduction in cell division) when added individually to human melanoma cells in culture. However, the combination of sodium butyrate with one of the cyclic AMP-stimulating agents produced a marked reduction in cell number (primarily due to cell death)."}
{"id": "PMID:215451", "title": "[Isolation by affinity chromatography of specialized membrane fractions from cat liver microsomes].", "content": "Microsomal glucokinase is solubilized by incubation in the presence of several metabolites. After solubilization of the enzymes, the membranes present free sites for specific binding of glucokinase, therefore, they can be purified by affinity chromatography on Sepharose--ATP-glucokinase. This method yields membranous vesicles which contain, in addition to glucokinase, uridylyl-transferase, phosphoglucomutase, sialyl-transferase and adenylate cyclase. Galactosyl-transferase, glucose-6-phosphatase and NADPH cytochrome c reductase are absent. It appears that functionally related enzyme from UDP-glucose biosynthesis are aggregated onto specific patches of the membrane, most likely from Golgi apparatus.", "contents": "[Isolation by affinity chromatography of specialized membrane fractions from cat liver microsomes]. Microsomal glucokinase is solubilized by incubation in the presence of several metabolites. After solubilization of the enzymes, the membranes present free sites for specific binding of glucokinase, therefore, they can be purified by affinity chromatography on Sepharose--ATP-glucokinase. This method yields membranous vesicles which contain, in addition to glucokinase, uridylyl-transferase, phosphoglucomutase, sialyl-transferase and adenylate cyclase. Galactosyl-transferase, glucose-6-phosphatase and NADPH cytochrome c reductase are absent. It appears that functionally related enzyme from UDP-glucose biosynthesis are aggregated onto specific patches of the membrane, most likely from Golgi apparatus."}
{"id": "PMID:215462", "title": "Central mechanisms of fever.", "content": "The possible role of various potential chemical mediators in the production of fever is reviewed. A major problem in this field is the very considerable conflict of evidence, let alone interpretation. On the existing evidence, it appears unlikely that monoamines, acetyl choline, or alterations in relative concentrations of sodium and calcium play any major role in the production of fever. Recent evidence makes it unlikely that prostaglandins have a direct role in this mechanism, though the involvement of other metabolites of arachidonic acid has not been excluded. It is possible that protein synthesis may play a part in the central action of leukocyte pyrogen.", "contents": "Central mechanisms of fever. The possible role of various potential chemical mediators in the production of fever is reviewed. A major problem in this field is the very considerable conflict of evidence, let alone interpretation. On the existing evidence, it appears unlikely that monoamines, acetyl choline, or alterations in relative concentrations of sodium and calcium play any major role in the production of fever. Recent evidence makes it unlikely that prostaglandins have a direct role in this mechanism, though the involvement of other metabolites of arachidonic acid has not been excluded. It is possible that protein synthesis may play a part in the central action of leukocyte pyrogen."}
{"id": "PMID:215463", "title": "The role of prostacyclin in vascular tissue.", "content": "Prostacyclin (PGI2) generated by the vascular wall is a potent vasodilator, and the most potent endogenous inhibitor of platelet aggregation so far discovered. Prostacyclin inhibits platelet aggregation by increasing cyclic AMP levels. Prostacyclin is a circulating hormone continually released by the lungs into the arterial circulation. Circulating platelets are, therefore, subjected constantly to prostacyclin stimulation and it is via this mechanism that platelet aggregability in vivo is controlled. Moreover, phosphodiesterase inhibitors such as dipyridamole or theophylline exert their antithrombotic actions by potentiating circulating prostacyclin. The prostacyclin:thromboxane A2 ratio is important in the control of thrombus formation; manipulation of this ratio by small doses of aspirin (which will inhibit mainly platelet cyclooxygenase), a selective inhibitor of thromboxane formation, or the dietary use of a fatty acid like eicosapentaenoic acid (which would be the precursor for a delta17-prostacyclin (PGI3) but is transformed by the platelets into nonaggregating thromboxane A3) might have beneficial effects as antithrombotic therapies. Prostacyclin has interesting potential for clinical application in conditions where enhanced platelet aggregation is involved or to increase biocompatibility of extracorporeal circulation systems.", "contents": "The role of prostacyclin in vascular tissue. Prostacyclin (PGI2) generated by the vascular wall is a potent vasodilator, and the most potent endogenous inhibitor of platelet aggregation so far discovered. Prostacyclin inhibits platelet aggregation by increasing cyclic AMP levels. Prostacyclin is a circulating hormone continually released by the lungs into the arterial circulation. Circulating platelets are, therefore, subjected constantly to prostacyclin stimulation and it is via this mechanism that platelet aggregability in vivo is controlled. Moreover, phosphodiesterase inhibitors such as dipyridamole or theophylline exert their antithrombotic actions by potentiating circulating prostacyclin. The prostacyclin:thromboxane A2 ratio is important in the control of thrombus formation; manipulation of this ratio by small doses of aspirin (which will inhibit mainly platelet cyclooxygenase), a selective inhibitor of thromboxane formation, or the dietary use of a fatty acid like eicosapentaenoic acid (which would be the precursor for a delta17-prostacyclin (PGI3) but is transformed by the platelets into nonaggregating thromboxane A3) might have beneficial effects as antithrombotic therapies. Prostacyclin has interesting potential for clinical application in conditions where enhanced platelet aggregation is involved or to increase biocompatibility of extracorporeal circulation systems."}
{"id": "PMID:215466", "title": "[Effect of hirudin on hormonally caused activation of nonenzymatic fibrinolysis in immobilization stress].", "content": "The specific inhibitor of thrombin-hirudin was used for studying the mechanism of activating effect of ACTH and adrenaline upon the unenzymatic fibrinolysis (UEF), the latter characterizing the function of the anticoagulating system (ACS). Simultaneous administration of ACTH and hirudin to animals subjected to the immobilization stress did not reduce the effect of ACTH upon UEF, while simultaneous administration of adrenaline and hirudin revealed a diminished effect of the former. This suggests different mechanisms of ACTH and adrenaline effects upon UEF: the stimulating effect of noradrenaline is realized through thrombinogenesis followed by activation of the ACS function and by an increase of UEF and therefore inhibitable by hirudin which form an inactive complex with thrombin. While the stimulating effect of ACTH upon UEF is exerted, apparently, not through thrombinogenesis and hence is valid even in presence of hirudin. Hirudin proper exerts no effect upon UEF.", "contents": "[Effect of hirudin on hormonally caused activation of nonenzymatic fibrinolysis in immobilization stress]. The specific inhibitor of thrombin-hirudin was used for studying the mechanism of activating effect of ACTH and adrenaline upon the unenzymatic fibrinolysis (UEF), the latter characterizing the function of the anticoagulating system (ACS). Simultaneous administration of ACTH and hirudin to animals subjected to the immobilization stress did not reduce the effect of ACTH upon UEF, while simultaneous administration of adrenaline and hirudin revealed a diminished effect of the former. This suggests different mechanisms of ACTH and adrenaline effects upon UEF: the stimulating effect of noradrenaline is realized through thrombinogenesis followed by activation of the ACS function and by an increase of UEF and therefore inhibitable by hirudin which form an inactive complex with thrombin. While the stimulating effect of ACTH upon UEF is exerted, apparently, not through thrombinogenesis and hence is valid even in presence of hirudin. Hirudin proper exerts no effect upon UEF."}
{"id": "PMID:215467", "title": "[Interorgan metabolic correlations during muscular activity and fatigue].", "content": "Biochemical and mathematical analysis revealed that metabolic processes in muscles, blood, liver, and brain during both unfatiguing muscular activity and in fatigue change their correlative bonds not identealby. The experiments exposed as a common traits, as differences in metabolic structure of both rapidly and slowly developed fatigue.", "contents": "[Interorgan metabolic correlations during muscular activity and fatigue]. Biochemical and mathematical analysis revealed that metabolic processes in muscles, blood, liver, and brain during both unfatiguing muscular activity and in fatigue change their correlative bonds not identealby. The experiments exposed as a common traits, as differences in metabolic structure of both rapidly and slowly developed fatigue."}
{"id": "PMID:215470", "title": "The influence of Triton X-100 on the nuclear envelope of the isolated liver cell nuclei.", "content": "In order to obtain more precise information on an eventual presence of extra-membranous lipids in the interior of the nucleus, the effects of Triton X-100 on the lipid content and ultrastructure of isolated rat liver nuclei was investigated. Enzyme markers (a.o. glucose-6-phosphatase) were used to control impurities of the nuclear fractions biochemically along with transmission electron microscopy and qualitative and quantitative light microscopy to check the condition of the nuclei obtained. Treatment of the nuclear fraction with increasing concentrations of Triton X-100 resulted in a decrease of the phospholipid content down to 25% at a Triton X-100/protein ratio of 0.4. A further decrease to 8% was measured at a ratio of 1.5. Electron microscopy of nuclei of the latter group showed nuclei containing outer membrane fragments in 2.5% of their surfaces. The composition of lipids extracted from a nuclear fraction appeared to be markedly changed after treatment with Triton X-100 with an increase of the percentage of neutral lipids and the phospholipids diphosphatidyl-glycerol and spingomyelin. From the chemical and morphological data obtained, the conclusion was drawn that a substantial part of the lipids remaining in the isolated nuclei after treatment with Triton X-100 is localized in both membranes of the nuclear envelope. It cannot however, be excluded that a small portion would be present in the interior of the nuclei.", "contents": "The influence of Triton X-100 on the nuclear envelope of the isolated liver cell nuclei. In order to obtain more precise information on an eventual presence of extra-membranous lipids in the interior of the nucleus, the effects of Triton X-100 on the lipid content and ultrastructure of isolated rat liver nuclei was investigated. Enzyme markers (a.o. glucose-6-phosphatase) were used to control impurities of the nuclear fractions biochemically along with transmission electron microscopy and qualitative and quantitative light microscopy to check the condition of the nuclei obtained. Treatment of the nuclear fraction with increasing concentrations of Triton X-100 resulted in a decrease of the phospholipid content down to 25% at a Triton X-100/protein ratio of 0.4. A further decrease to 8% was measured at a ratio of 1.5. Electron microscopy of nuclei of the latter group showed nuclei containing outer membrane fragments in 2.5% of their surfaces. The composition of lipids extracted from a nuclear fraction appeared to be markedly changed after treatment with Triton X-100 with an increase of the percentage of neutral lipids and the phospholipids diphosphatidyl-glycerol and spingomyelin. From the chemical and morphological data obtained, the conclusion was drawn that a substantial part of the lipids remaining in the isolated nuclei after treatment with Triton X-100 is localized in both membranes of the nuclear envelope. It cannot however, be excluded that a small portion would be present in the interior of the nuclei."}
{"id": "PMID:215471", "title": "Visualization of mouse DNA transcriptional complexes in mouse kidney cells infected with SV 40 virus.", "content": "Electron microscopic studies of transcribed cellular deoxynucleoprotein (DNP) fibers from mouse kidney cells abortively infected with Simian Virus 40 (SV 40) revealed two types of transcriptional complexes. Tandemly repeating units representing ribosomal transcriptional events, although few in number because of the procedure employed, clearly confirmed results of other techniques which revealed the unusually long length of the untranscribed spacer intercepts in mouse nucleolar chromatin. In non-nucleolar arrays the density of the ribonucleoprotein (RNP) fibrils varied, as did the length and configuration of the associated DNP fibers. A statistical correlation between a \"smooth\" appearance of a transcribed portion of a DNP fiber and a high density of nascent RNP fibrils was observed.", "contents": "Visualization of mouse DNA transcriptional complexes in mouse kidney cells infected with SV 40 virus. Electron microscopic studies of transcribed cellular deoxynucleoprotein (DNP) fibers from mouse kidney cells abortively infected with Simian Virus 40 (SV 40) revealed two types of transcriptional complexes. Tandemly repeating units representing ribosomal transcriptional events, although few in number because of the procedure employed, clearly confirmed results of other techniques which revealed the unusually long length of the untranscribed spacer intercepts in mouse nucleolar chromatin. In non-nucleolar arrays the density of the ribonucleoprotein (RNP) fibrils varied, as did the length and configuration of the associated DNP fibers. A statistical correlation between a \"smooth\" appearance of a transcribed portion of a DNP fiber and a high density of nascent RNP fibrils was observed."}
{"id": "PMID:215472", "title": "Plasma cyclic AMP response to glucagon as an index of tissue responsiveness to thyroid hormone.", "content": "The rise in plasma cyclic AMP after glucagon has been studied in hyper- and hypothyroid patients before and after treatment. In the hyperthyroid group, each individual patient showed a decrease in cyclic AMP response to glucagon on becoming euthyroid, but there was no change after treatment with propranolol. In the hypothyroid group, each individual patient showed an increase in response on becoming euthyroid on thyroxine. We suggest that peak plasma cyclic AMP response to glucagon could be used to monitor tissue responisveness to thyroid hormone during treatment of hypo- and hyperthyroidism, though change in this response is a more sensitive indicator of change from the hypothyroid to the euthyroid state than from the hyperthyroid to the euthyroid state.", "contents": "Plasma cyclic AMP response to glucagon as an index of tissue responsiveness to thyroid hormone. The rise in plasma cyclic AMP after glucagon has been studied in hyper- and hypothyroid patients before and after treatment. In the hyperthyroid group, each individual patient showed a decrease in cyclic AMP response to glucagon on becoming euthyroid, but there was no change after treatment with propranolol. In the hypothyroid group, each individual patient showed an increase in response on becoming euthyroid on thyroxine. We suggest that peak plasma cyclic AMP response to glucagon could be used to monitor tissue responisveness to thyroid hormone during treatment of hypo- and hyperthyroidism, though change in this response is a more sensitive indicator of change from the hypothyroid to the euthyroid state than from the hyperthyroid to the euthyroid state."}
{"id": "PMID:215473", "title": "[Pancreatic polypeptide (author's transl)].", "content": "Pancreatic Polypeptide (PP) was first described in birds by Kimmel et al. (1968). It was later isolated from the pancreas of several mammalian species by Chance and Jones (1974). It has been demonstrated in the islets of many animal species by immunocytochemical methods. PP levels are assayable in plasma and rise sharply after food intake. The pharmacological properties and physiological role of PP are still ill defined. It appears to have a spectrum of actions peculiar to each species. Recent research on this subject is reviewed in this article. High levels of circulating PP have been demonstrated in juvenile and maturity-onset diabetics, as well as in some patients with islet cell tumors. However no definite clinical syndrome due to hypersecretion of PP as been identified as yet. It remains a matter of speculation that a deficiency of PP might be responsible for some types of obesity. PP-cells are rare in the pancreas of healthy young individuals. Hyperplasia of PP-cells has been observed in a wide variety of pathological conditions, but is most prominent in the pancreas of chronic insulin dependent diabetics. Histologic evidence strongly suggests that PP-cell hyperplasia represents an atypical form of islet regeneration. It is always focal in distribution and is most remarkable in those lobules that have lost the capacity to reproduce islets of normal cytologic composition.", "contents": "[Pancreatic polypeptide (author's transl)]. Pancreatic Polypeptide (PP) was first described in birds by Kimmel et al. (1968). It was later isolated from the pancreas of several mammalian species by Chance and Jones (1974). It has been demonstrated in the islets of many animal species by immunocytochemical methods. PP levels are assayable in plasma and rise sharply after food intake. The pharmacological properties and physiological role of PP are still ill defined. It appears to have a spectrum of actions peculiar to each species. Recent research on this subject is reviewed in this article. High levels of circulating PP have been demonstrated in juvenile and maturity-onset diabetics, as well as in some patients with islet cell tumors. However no definite clinical syndrome due to hypersecretion of PP as been identified as yet. It remains a matter of speculation that a deficiency of PP might be responsible for some types of obesity. PP-cells are rare in the pancreas of healthy young individuals. Hyperplasia of PP-cells has been observed in a wide variety of pathological conditions, but is most prominent in the pancreas of chronic insulin dependent diabetics. Histologic evidence strongly suggests that PP-cell hyperplasia represents an atypical form of islet regeneration. It is always focal in distribution and is most remarkable in those lobules that have lost the capacity to reproduce islets of normal cytologic composition."}
{"id": "PMID:215474", "title": "Influence of bromoergocryptine on estrogen-modulated prolactin receptors of mouse mammary gland.", "content": "Modulation of specific binding of prolactin to murine mammary gland as a response to treatment with various doses of estradiol benzoate (EB) was studied. Measurements of serum and pituitary levels of prolactin were also carried out simultaneously. Estradiol benzoate at a dose of 5 microgram significantly increased the binding of 125I-labelled rat prolactin (rPRL) to mammary gland concomitant with increased serum prolactin levels in ovariectomized mice. Administration of bromoergocryptine along with EB resulted in decreased serum prolactin levels as well as binding of prolactin to breast tissue. It thus appears that the influence of estradiol on binding of prolactin to mammary gland is mediated primarily via its property of enhancing serum prolactin concentration apart from its possible direct effect at the target tissue level.", "contents": "Influence of bromoergocryptine on estrogen-modulated prolactin receptors of mouse mammary gland. Modulation of specific binding of prolactin to murine mammary gland as a response to treatment with various doses of estradiol benzoate (EB) was studied. Measurements of serum and pituitary levels of prolactin were also carried out simultaneously. Estradiol benzoate at a dose of 5 microgram significantly increased the binding of 125I-labelled rat prolactin (rPRL) to mammary gland concomitant with increased serum prolactin levels in ovariectomized mice. Administration of bromoergocryptine along with EB resulted in decreased serum prolactin levels as well as binding of prolactin to breast tissue. It thus appears that the influence of estradiol on binding of prolactin to mammary gland is mediated primarily via its property of enhancing serum prolactin concentration apart from its possible direct effect at the target tissue level."}
{"id": "PMID:215475", "title": "On the role of protein synthesis in the response of adrenal tumor cells to ACTH.", "content": "Y-1 adrenal tumor cells were incubated with aminoglutethimide with and without ACTH. Greater production of pregnenolone from endogenous cholesterol was observed (after washing to remove aminoglutethimide) in mitochondria from cells incubated with aminoglutethimide and ACTH than in those from cells incubated with aminoglutethimide alone. This response was inhibited by cycloheximide and puromycin but not by chloramphenicol or actinomycin D. ACTH increased the incorporation of [3H]tyrosine into protein associated with mitochondria but not into total cell protein or protein of postmitochondrial supernatant. This response did not require aminoglutethemide block and was inhibited by cycloheximide and puromycin but not by chloramphenicol or actinomycin D. Dibutyryl cyclic AMP produced both of these responses (increased production of pregnenolone and synthesis of protein associated with mitochondria). The concentration of cycloheximide required to cause 50% inhibition of the responses to ACTH and dibutyryl cyclic AMP was approximately the same for steroidogenesis by whole cells, for production of pregnenolone by isolated mitochondria, for incorporation of [3H]tyrosine into Y-1 cell protein and for the increase in synthesis of protein associated with mitochondria produced by ACTH (0.08--0.2 microgram/ml). Disc gel electrophoresis revealed that the increased incorporation of [3H]tyrosine involved two proteins corresponding to molecular weight of approximately 27,000 and 13,000 respectively. These observations suggest that ACTH promotes synthesis of protein(s) by cytoplasmic ribosomes on stable messenger RNA, that the protein(s) becomes associated with mitochondria and that the protein(s) includes one or more which are associated with the increase in production of pregnenolone produced in mitochondria by the addition of ACTH to adrenal cells.", "contents": "On the role of protein synthesis in the response of adrenal tumor cells to ACTH. Y-1 adrenal tumor cells were incubated with aminoglutethimide with and without ACTH. Greater production of pregnenolone from endogenous cholesterol was observed (after washing to remove aminoglutethimide) in mitochondria from cells incubated with aminoglutethimide and ACTH than in those from cells incubated with aminoglutethimide alone. This response was inhibited by cycloheximide and puromycin but not by chloramphenicol or actinomycin D. ACTH increased the incorporation of [3H]tyrosine into protein associated with mitochondria but not into total cell protein or protein of postmitochondrial supernatant. This response did not require aminoglutethemide block and was inhibited by cycloheximide and puromycin but not by chloramphenicol or actinomycin D. Dibutyryl cyclic AMP produced both of these responses (increased production of pregnenolone and synthesis of protein associated with mitochondria). The concentration of cycloheximide required to cause 50% inhibition of the responses to ACTH and dibutyryl cyclic AMP was approximately the same for steroidogenesis by whole cells, for production of pregnenolone by isolated mitochondria, for incorporation of [3H]tyrosine into Y-1 cell protein and for the increase in synthesis of protein associated with mitochondria produced by ACTH (0.08--0.2 microgram/ml). Disc gel electrophoresis revealed that the increased incorporation of [3H]tyrosine involved two proteins corresponding to molecular weight of approximately 27,000 and 13,000 respectively. These observations suggest that ACTH promotes synthesis of protein(s) by cytoplasmic ribosomes on stable messenger RNA, that the protein(s) becomes associated with mitochondria and that the protein(s) includes one or more which are associated with the increase in production of pregnenolone produced in mitochondria by the addition of ACTH to adrenal cells."}
{"id": "PMID:215476", "title": "Occupancy of aldosterone binding sites in rat kidney cytosol.", "content": "The binding sites for aldosterone and a potent aldosterone antagonist (SC-26304) were studied in kidney cytosol from adrenalectomized rats. Preformed cytosol and kidney slices were incubated with 3H-labeled steroids in a wide range of concentrations. The recovery and characteristics of the binding sites were affected by the incubation and homogenization conditions. High-affinity, Type I mineralocorticoid binding was reduced by more than 95% when cytosol was incubated at 25 degrees C in the presence of calcium. Tissue dilution also affected the binding sites. SC-26304 was bound to high- and low-affinity receptors, similar to the binding of aldosterone. The physiologic response to aldosterone could result from binding to either or both sets of sites. Some of the physiologic responses to spirolactones could represent antagonism of the binding of aldosterone to either or both sites. A convenient method is presented for describing the relative occupancy of several different sites by any particular steroid.", "contents": "Occupancy of aldosterone binding sites in rat kidney cytosol. The binding sites for aldosterone and a potent aldosterone antagonist (SC-26304) were studied in kidney cytosol from adrenalectomized rats. Preformed cytosol and kidney slices were incubated with 3H-labeled steroids in a wide range of concentrations. The recovery and characteristics of the binding sites were affected by the incubation and homogenization conditions. High-affinity, Type I mineralocorticoid binding was reduced by more than 95% when cytosol was incubated at 25 degrees C in the presence of calcium. Tissue dilution also affected the binding sites. SC-26304 was bound to high- and low-affinity receptors, similar to the binding of aldosterone. The physiologic response to aldosterone could result from binding to either or both sets of sites. Some of the physiologic responses to spirolactones could represent antagonism of the binding of aldosterone to either or both sites. A convenient method is presented for describing the relative occupancy of several different sites by any particular steroid."}
{"id": "PMID:215478", "title": "Mucosal enzyme patterns in gastric epithelial disease.", "content": "A correlation was sought between changes in enzymes involved in gastric acid secretion (Mg-, NaK-, K- and HCO3-stimulated ATPases) and histological changes in gastric biopsies. Alkaline phosphatase was also studied. Mg- and NaK-stimulated ATPase activities increased significantly in biopsies from the pylorus and antrum which showed moderate or severe gastritis. NaK ATPase levels increased and HCO3 ATPase decreased in incisural, body and fundic mucosa which had intestinal metaplasia and atrophic gastritis. No K+ ATPase was found in normal mucosa. The total activity of alkaline phosphatase did not vary with histological changes in the gastric mucosa. Results indicate that the ATPase enzyme systems are sensitive indicators of gastric mucosal disease.", "contents": "Mucosal enzyme patterns in gastric epithelial disease. A correlation was sought between changes in enzymes involved in gastric acid secretion (Mg-, NaK-, K- and HCO3-stimulated ATPases) and histological changes in gastric biopsies. Alkaline phosphatase was also studied. Mg- and NaK-stimulated ATPase activities increased significantly in biopsies from the pylorus and antrum which showed moderate or severe gastritis. NaK ATPase levels increased and HCO3 ATPase decreased in incisural, body and fundic mucosa which had intestinal metaplasia and atrophic gastritis. No K+ ATPase was found in normal mucosa. The total activity of alkaline phosphatase did not vary with histological changes in the gastric mucosa. Results indicate that the ATPase enzyme systems are sensitive indicators of gastric mucosal disease."}
{"id": "PMID:215479", "title": "The influence of the major histocompatibility complex (H-2) on experimental diabetes in mice.", "content": "Mice with different histocompatibility loci on an identical background genome (congenic resistant lines of mice) were used to study the possible influence of the histocompatibility complex on experimental diabetes. The major histocompatibility complex (H-2) was not found to influence the diabetogenic effect of encephalomyocarditis (EMC) virus. In contrast the glucose intolerance following heterologous and homologous immunization with pancreatic antigens appeared H-2 influenced. Antibodies against cell surface components on viable B-cells were present in serum from mice with glucose intolerance induced by homologous immunization. The results suggest that the susceptibility to experimental autoimmune diabetes in mice is influenced by the H-2 complex.", "contents": "The influence of the major histocompatibility complex (H-2) on experimental diabetes in mice. Mice with different histocompatibility loci on an identical background genome (congenic resistant lines of mice) were used to study the possible influence of the histocompatibility complex on experimental diabetes. The major histocompatibility complex (H-2) was not found to influence the diabetogenic effect of encephalomyocarditis (EMC) virus. In contrast the glucose intolerance following heterologous and homologous immunization with pancreatic antigens appeared H-2 influenced. Antibodies against cell surface components on viable B-cells were present in serum from mice with glucose intolerance induced by homologous immunization. The results suggest that the susceptibility to experimental autoimmune diabetes in mice is influenced by the H-2 complex."}
{"id": "PMID:215480", "title": "Effects of alloxan on glucose-stimulated insulin secretion, glucose metabolism, and cyclic adenosine 3', 5'-monophosphate levels in rat isolated islets of langerhans.", "content": "Insulin secretion was stimulated and cyclic adenosine 3', 5'-monophosphate (cAMP) levels were elevated in isolated rat islets by 27.5 mmol/l glucose. Alloxan caused a dose-dependent decrease in both variables with complete obliteration of insulin release at a concentration of 1.25 mmol/l. D-glucose, in the presence or absence of extracellular calcium, or 3-0-methyl-D-glucose (both at 27.5 mmol/l) protected completely against the effects of alloxan on both glucose-induced insulin release and cAMP Levels. 3-0-Methylglucose did not stimulate insulin secretion or elevate cAMP and did not interfere with glucose-stimulated secretion or elevation of cAMP. When glucose-stimulated insulin release was abolished by alloxan, the metabolism of glucose, determined by the rate of 3H2O formation from [5-3H] glucose, was depressed by 20%. It is concluded that alloxan altered the adenylate cyclase system such that it could no longer be stimulated by glucose. Glucose-stimulated insulin secretion or elevation of cAMP did not appear essential for glucose to protect against alloxan. Protection by 3-0-methylglucose did not appear to be mediated through an alteration of cAMP metabolism. Alloxan did not inhibit glucose-induced insulin secretion by grossly altering glycolysis.", "contents": "Effects of alloxan on glucose-stimulated insulin secretion, glucose metabolism, and cyclic adenosine 3', 5'-monophosphate levels in rat isolated islets of langerhans. Insulin secretion was stimulated and cyclic adenosine 3', 5'-monophosphate (cAMP) levels were elevated in isolated rat islets by 27.5 mmol/l glucose. Alloxan caused a dose-dependent decrease in both variables with complete obliteration of insulin release at a concentration of 1.25 mmol/l. D-glucose, in the presence or absence of extracellular calcium, or 3-0-methyl-D-glucose (both at 27.5 mmol/l) protected completely against the effects of alloxan on both glucose-induced insulin release and cAMP Levels. 3-0-Methylglucose did not stimulate insulin secretion or elevate cAMP and did not interfere with glucose-stimulated secretion or elevation of cAMP. When glucose-stimulated insulin release was abolished by alloxan, the metabolism of glucose, determined by the rate of 3H2O formation from [5-3H] glucose, was depressed by 20%. It is concluded that alloxan altered the adenylate cyclase system such that it could no longer be stimulated by glucose. Glucose-stimulated insulin secretion or elevation of cAMP did not appear essential for glucose to protect against alloxan. Protection by 3-0-methylglucose did not appear to be mediated through an alteration of cAMP metabolism. Alloxan did not inhibit glucose-induced insulin secretion by grossly altering glycolysis."}
{"id": "PMID:215481", "title": "Changes in intramembranous particle topography and concanavalin A receptor mobility associated with myoblast differentiation.", "content": "These studies have examined the distribution of plasma membrane intramembranous particles (PMP) visualized by freeze fracture and concanavalin A receptors seen by ultrastructural cytochemistry of differentiated and undifferentiated L6 myoblasts. Undifferentiated mononucleated cells have a clustered distribution of PMP on the majority of the fracture faces. Associated with cell differentiation and cell fusion a more uniform distribution of PMP is observed. Changes also occur with myoblast differentiation in the topography and dynamics of receptors bound to concanavalin A. If undifferentiated or differentiated cells are fixed with glutaraldehyde and then reacted with con-A a uniform distribution of con-A is seen on the cell surfaces. In contrast to this if unfixed live cells are reacted at 37 degrees C with con-A a profound redistribution occurs on differentiated cells (greater than 99% showing redistribution) while receptors remain in a uniform array on undifferentiated cells (approximately 95% uniform distribution). In addition to the membrane binding, con-A is observed to bind to an extracellular filamentous matrix seen in high density undifferentiated cultures which then appears to be degraded with differentiation and myoblast fusion. These studies show that a number of membrane changes, both structural and dynamic occur with myoblast differentiation.", "contents": "Changes in intramembranous particle topography and concanavalin A receptor mobility associated with myoblast differentiation. These studies have examined the distribution of plasma membrane intramembranous particles (PMP) visualized by freeze fracture and concanavalin A receptors seen by ultrastructural cytochemistry of differentiated and undifferentiated L6 myoblasts. Undifferentiated mononucleated cells have a clustered distribution of PMP on the majority of the fracture faces. Associated with cell differentiation and cell fusion a more uniform distribution of PMP is observed. Changes also occur with myoblast differentiation in the topography and dynamics of receptors bound to concanavalin A. If undifferentiated or differentiated cells are fixed with glutaraldehyde and then reacted with con-A a uniform distribution of con-A is seen on the cell surfaces. In contrast to this if unfixed live cells are reacted at 37 degrees C with con-A a profound redistribution occurs on differentiated cells (greater than 99% showing redistribution) while receptors remain in a uniform array on undifferentiated cells (approximately 95% uniform distribution). In addition to the membrane binding, con-A is observed to bind to an extracellular filamentous matrix seen in high density undifferentiated cultures which then appears to be degraded with differentiation and myoblast fusion. These studies show that a number of membrane changes, both structural and dynamic occur with myoblast differentiation."}
{"id": "PMID:215485", "title": "Clinical significance of mitochondrial glutamic-oxaloacetic transaminase in serum of patients with liver disease.", "content": "Serum mitochondrial glutamic-oxaloacetic transaminase activity was determined in 83 patients with various liver diseases and 10 healthy adults. 1) The average of mitochondrial glutamic-oxaloacetic transaminase value was 1.2 mU in healthy adults, 8.3 mU in patients with acute hepatitis, 13.7 mU in patients with post-transfusion hepatitis, 5.0 mU in patients with persistent hepatitis, 4.5 mU in patients with chronic inactive hepatitis, 9.6 mU in patients with chronic active hepatitis, 5.6 mU in liver cirrhosis, and 295 mU in a patient with fulminant hepatitis. 2) While one patient with acute hepatitis showed the highest value in the group of 29 mU, one patient with fulminant hepatitis showed an extremely high value of 295 mU, revealing an obvious difference between them. 3) One patient with fresh myocardial infarction also showed an extremely high value of 110 mU.", "contents": "Clinical significance of mitochondrial glutamic-oxaloacetic transaminase in serum of patients with liver disease. Serum mitochondrial glutamic-oxaloacetic transaminase activity was determined in 83 patients with various liver diseases and 10 healthy adults. 1) The average of mitochondrial glutamic-oxaloacetic transaminase value was 1.2 mU in healthy adults, 8.3 mU in patients with acute hepatitis, 13.7 mU in patients with post-transfusion hepatitis, 5.0 mU in patients with persistent hepatitis, 4.5 mU in patients with chronic inactive hepatitis, 9.6 mU in patients with chronic active hepatitis, 5.6 mU in liver cirrhosis, and 295 mU in a patient with fulminant hepatitis. 2) While one patient with acute hepatitis showed the highest value in the group of 29 mU, one patient with fulminant hepatitis showed an extremely high value of 295 mU, revealing an obvious difference between them. 3) One patient with fresh myocardial infarction also showed an extremely high value of 110 mU."}
{"id": "PMID:215486", "title": "Studies on the outbreak of hepatitis A in an institute for mentally retarded children.", "content": "The authors encountered an outbreak of acute hepatitis in a public institute for mentally retarded children in Aomori Prefecture, Japan. Studies revealed that the probable vehicles of transmission of infection were contaminated water, contaminated meals, and close contact. From the clinical manifestations and epidemiological investigations of 41 affected children and staff members, an outbreak of hepatitis A was strongly suspected. Immune electron microscopy disclosed hepatitis A virus antigen particles in the stool specimens collected during the few days before and after peak transaminase elevation. Hepatitis A antigen was further extracted and purified. The antigen was the first reported recovery of the virus from a natural outbreak of hapatitis A in Asia. Subsequently, with the immune adherence hemagglutination test, using this extracted antigen, an increase in titer of antibody to hepatitis A antigen was demonstrated. Thus, this epidemic was serologically established as an outbreak of hepatitis A. Human immune serum globulin for the protection against hepatitis A was administrated to the 80 individuals concerned, and it was effective in preventing the clinical manifestation of hepatitis.", "contents": "Studies on the outbreak of hepatitis A in an institute for mentally retarded children. The authors encountered an outbreak of acute hepatitis in a public institute for mentally retarded children in Aomori Prefecture, Japan. Studies revealed that the probable vehicles of transmission of infection were contaminated water, contaminated meals, and close contact. From the clinical manifestations and epidemiological investigations of 41 affected children and staff members, an outbreak of hepatitis A was strongly suspected. Immune electron microscopy disclosed hepatitis A virus antigen particles in the stool specimens collected during the few days before and after peak transaminase elevation. Hepatitis A antigen was further extracted and purified. The antigen was the first reported recovery of the virus from a natural outbreak of hapatitis A in Asia. Subsequently, with the immune adherence hemagglutination test, using this extracted antigen, an increase in titer of antibody to hepatitis A antigen was demonstrated. Thus, this epidemic was serologically established as an outbreak of hepatitis A. Human immune serum globulin for the protection against hepatitis A was administrated to the 80 individuals concerned, and it was effective in preventing the clinical manifestation of hepatitis."}
{"id": "PMID:215487", "title": "Serum ribonucleases in pancreatic cancer: relation to tumor histology.", "content": "Serum Ribonuclease (RNase, EC. 3. 1. 4. 22) of normal persons and of patients with chronic pancreatitis, or pancreatic cancer was determined with poly (C) as substrate. Strikingly abnormal elevations occured in the serum RNase of patients with pancreatic cancer (p less than 0.001). Average serum RNase values of 18 normal persons, 10 patients with chronic pancreatitis and 26 patients with pancreatic cancer were 92, 118, and 249 units, respectively. In patients with pancreatic cancer, we compared the RNase level with four histologic types (ductar cell adenocarcinoma, anaplastic cell carcinoma, acinar cell carcinoma, and islet cell carcinoma). Adenocarcinoma showed higher activity than the other histologic types (p less than 0.005). When we compared the serum of pancreatic cancer and pancreatic cancer tumor extract with normal serum and normal pancreas extract, strikingly different phosphocellulose chromatographic pattern were evident. The correlation of increased serum RNase levels with tumor histology and different chromatographic pattern may explain the new enzyme production in cancer patients, and have biological significance in the development of pancreatic cancer.", "contents": "Serum ribonucleases in pancreatic cancer: relation to tumor histology. Serum Ribonuclease (RNase, EC. 3. 1. 4. 22) of normal persons and of patients with chronic pancreatitis, or pancreatic cancer was determined with poly (C) as substrate. Strikingly abnormal elevations occured in the serum RNase of patients with pancreatic cancer (p less than 0.001). Average serum RNase values of 18 normal persons, 10 patients with chronic pancreatitis and 26 patients with pancreatic cancer were 92, 118, and 249 units, respectively. In patients with pancreatic cancer, we compared the RNase level with four histologic types (ductar cell adenocarcinoma, anaplastic cell carcinoma, acinar cell carcinoma, and islet cell carcinoma). Adenocarcinoma showed higher activity than the other histologic types (p less than 0.005). When we compared the serum of pancreatic cancer and pancreatic cancer tumor extract with normal serum and normal pancreas extract, strikingly different phosphocellulose chromatographic pattern were evident. The correlation of increased serum RNase levels with tumor histology and different chromatographic pattern may explain the new enzyme production in cancer patients, and have biological significance in the development of pancreatic cancer."}
{"id": "PMID:215488", "title": "Hepatocellular carcinoma in the U.S.A., etiologic considerations. Localization of hepatitis B antigens.", "content": "The serologic and tissue markers of hepatitis B virus (HBV) were studied in 50 patients in whom hepatocellular carcinoma (HCC) was confirmed at autopsy. Serologic and tissue markers included serum hepatitis B surface antigen (HBsAg), tissue HBsAg, tissue hepatitis core antigen (HBcAg), and serum antibody to HBcAg (anti-HBc). Twenty-two patients had HCC arising in alcoholic cirrhosis; 2 of the 22 (9.1%) had one or more of the HBV tissue and serologic markers. This infection rate is similar to the rate of 7.9% observed in 63 control alcoholic cirrhotic patients without HCC. In contrast, 15 of 20 (75.0%) patients with HCC in nonalcoholic chronic active liver disease showed evidence of active HBV infection. One of 8 patients with HCC in normal liver had serum HBV markers. This result indicates that there is an extremely high prevalence of HBV infection among HCC patients with nonalcoholic chronic liver disease in the U.S.A. The prevalence of HBV infection in these patients is as high as that observed in Asia and Africa. Thus, it can be concluded that the lower prevalence rate of active HBV infection in HCC patients in the U.S.A. is the result of statistical dilution of HCC-B-viral disease by the large numbers of the alcoholic cirrhotic patients with HCC, and that if chronic active hepatitis type B were as common in the United States as it is in Africa and Asia, the frequency of occurrence of HCC might also be as high.", "contents": "Hepatocellular carcinoma in the U.S.A., etiologic considerations. Localization of hepatitis B antigens. The serologic and tissue markers of hepatitis B virus (HBV) were studied in 50 patients in whom hepatocellular carcinoma (HCC) was confirmed at autopsy. Serologic and tissue markers included serum hepatitis B surface antigen (HBsAg), tissue HBsAg, tissue hepatitis core antigen (HBcAg), and serum antibody to HBcAg (anti-HBc). Twenty-two patients had HCC arising in alcoholic cirrhosis; 2 of the 22 (9.1%) had one or more of the HBV tissue and serologic markers. This infection rate is similar to the rate of 7.9% observed in 63 control alcoholic cirrhotic patients without HCC. In contrast, 15 of 20 (75.0%) patients with HCC in nonalcoholic chronic active liver disease showed evidence of active HBV infection. One of 8 patients with HCC in normal liver had serum HBV markers. This result indicates that there is an extremely high prevalence of HBV infection among HCC patients with nonalcoholic chronic liver disease in the U.S.A. The prevalence of HBV infection in these patients is as high as that observed in Asia and Africa. Thus, it can be concluded that the lower prevalence rate of active HBV infection in HCC patients in the U.S.A. is the result of statistical dilution of HCC-B-viral disease by the large numbers of the alcoholic cirrhotic patients with HCC, and that if chronic active hepatitis type B were as common in the United States as it is in Africa and Asia, the frequency of occurrence of HCC might also be as high."}
{"id": "PMID:215490", "title": "Antibodies to viral gastroenteritis viruses in Crohn's disease.", "content": "Antibody prevalence and titer to rotavirus and Norwalk virus were studied in Crohn's disease patients and in age-, sex-, and time-matched controls. There were no significant antibody differences between the groups studied.", "contents": "Antibodies to viral gastroenteritis viruses in Crohn's disease. Antibody prevalence and titer to rotavirus and Norwalk virus were studied in Crohn's disease patients and in age-, sex-, and time-matched controls. There were no significant antibody differences between the groups studied."}
{"id": "PMID:215495", "title": "A simple method for identifying the palindromic sequences recognized by restriction endonucleases: the nucleotide sequence of the AvaII site.", "content": "Tables specifying the frequencies, distances between and positions of all possible tetra-, penta- and hexanucleotide palindromes in phiX174 and SV40 viral DNAs were prepared by a computer search of their base sequences. A simple method based on these tables is described for identifying the sequence recognized by any specific restriction endonuclease. The method requires experimental determination of the number and approximate sizes of the fragments obtained by digestion of phiX174 RF and SV40 DNAs. Using this method we identified the sequence for AvaII restriction endonuclease as 5'-GG(AT)CC.", "contents": "A simple method for identifying the palindromic sequences recognized by restriction endonucleases: the nucleotide sequence of the AvaII site. Tables specifying the frequencies, distances between and positions of all possible tetra-, penta- and hexanucleotide palindromes in phiX174 and SV40 viral DNAs were prepared by a computer search of their base sequences. A simple method based on these tables is described for identifying the sequence recognized by any specific restriction endonuclease. The method requires experimental determination of the number and approximate sizes of the fragments obtained by digestion of phiX174 RF and SV40 DNAs. Using this method we identified the sequence for AvaII restriction endonuclease as 5'-GG(AT)CC."}
{"id": "PMID:215496", "title": "Hepatocellular carcinoma in Great Britain: influence of age, sex, HBsAg status, and aetiology of underlying cirrhosis.", "content": "An analysis of 294 patients who died with cirrhosis showed that 24% had developed hepatocellular carcinoma. Haemochromatosis and HBsAg positive chronic active hepatitis were high risk groups (36% and 42% respectively) and the frequency was lowest in primary biliary cirrhosis and HBsAg negative chronic active hepatitis (3% and 11% respectively). Those with hepatocellular carcinoma showed a striking male preponderance (11:1) and further analysis has shown that the proportion developing this tumour in each group was closely related to the proportion of males in that group (r=0.97). Age was the only other significant factor, malignant change occurring more commonly in those over the age of 50 years than those below (30% and 7% respectively, P less than 0.005). The indluence of HBsAg was largely accounted for by the known predisposition of males to carry HBsAg. The group of patients who had developed this tumour without cirrhosis were younger (mean age 39 years) and had a lower male to female ratio of 1.1:1 and the place of contraceptive-related tumour within this group is dicussed.", "contents": "Hepatocellular carcinoma in Great Britain: influence of age, sex, HBsAg status, and aetiology of underlying cirrhosis. An analysis of 294 patients who died with cirrhosis showed that 24% had developed hepatocellular carcinoma. Haemochromatosis and HBsAg positive chronic active hepatitis were high risk groups (36% and 42% respectively) and the frequency was lowest in primary biliary cirrhosis and HBsAg negative chronic active hepatitis (3% and 11% respectively). Those with hepatocellular carcinoma showed a striking male preponderance (11:1) and further analysis has shown that the proportion developing this tumour in each group was closely related to the proportion of males in that group (r=0.97). Age was the only other significant factor, malignant change occurring more commonly in those over the age of 50 years than those below (30% and 7% respectively, P less than 0.005). The indluence of HBsAg was largely accounted for by the known predisposition of males to carry HBsAg. The group of patients who had developed this tumour without cirrhosis were younger (mean age 39 years) and had a lower male to female ratio of 1.1:1 and the place of contraceptive-related tumour within this group is dicussed."}
{"id": "PMID:215498", "title": "[A method for percutaneous thin-needle biopsy of the pancreas aimed by ultrasound (author's transl)].", "content": "Percutaneous biopsy of the pancreas with a fine needle aimed by ultrasound was carried out on 26 patients with sonographically proven carcinoma of the pancreas. The accuracy of this method was correlated with other radiological techniques. Needle biopsy of the pancreas proved an informative and economical procedure, since the sonographic demonstration of a pancreatic mass otherwise requires additional radiological and endoscopic investigations.", "contents": "[A method for percutaneous thin-needle biopsy of the pancreas aimed by ultrasound (author's transl)]. Percutaneous biopsy of the pancreas with a fine needle aimed by ultrasound was carried out on 26 patients with sonographically proven carcinoma of the pancreas. The accuracy of this method was correlated with other radiological techniques. Needle biopsy of the pancreas proved an informative and economical procedure, since the sonographic demonstration of a pancreatic mass otherwise requires additional radiological and endoscopic investigations."}
{"id": "PMID:215499", "title": "[Genetic and biologic aspects of schizophrenias].", "content": "The results of investigations into the causes of schizophrenia--especially twin studies and adoption studies--support a genetic component to the transmission of schizophrenia. The exact mode of inheritance is still unknown. That what is inherited is probably a general tendency or disposition to psychopathology. Factors in the environment then elicit these tendencies or dispositions. The results of the biochemical investigations of schizophrenia and the consistent antidopamine effect of all antipsychotic agents support the idea that the dopamine synaptic neurotransmission may play an important role in the pathophysiology of schizophrenia.", "contents": "[Genetic and biologic aspects of schizophrenias]. The results of investigations into the causes of schizophrenia--especially twin studies and adoption studies--support a genetic component to the transmission of schizophrenia. The exact mode of inheritance is still unknown. That what is inherited is probably a general tendency or disposition to psychopathology. Factors in the environment then elicit these tendencies or dispositions. The results of the biochemical investigations of schizophrenia and the consistent antidopamine effect of all antipsychotic agents support the idea that the dopamine synaptic neurotransmission may play an important role in the pathophysiology of schizophrenia."}
{"id": "PMID:215500", "title": "Participation of L-ascorbate:ferricytochrome b5 oxidoreductase in ascorbate-dependent fatty acid desaturation of rat liver microsomes.", "content": "The microsomal enzyme ascorbate-cytochrome b5 reductase participates in the ascorbate-dependent fatty acid desaturation. Three pieces of evidence are given for this statement: 1) Comparison of the rate of ascorbate-dependent oleate formation with the rate of reduction of cytochrome b5 in microsomes and in the isolated detergent form shows that only the enzymatic reduction of cytochrome b5 is fast enough to support oleate formation; 2) added enriched ascorbate-cytochrome b5 reductase increases the rate of return of stearoyl-CoA oxidised cytochrome b5 back to the reduced state; 3) addition of enriched ascorbate-cytochrome b5 reductase increases the rate of ascorbate-dependent oleate formation in rat liver microsomes.", "contents": "Participation of L-ascorbate:ferricytochrome b5 oxidoreductase in ascorbate-dependent fatty acid desaturation of rat liver microsomes. The microsomal enzyme ascorbate-cytochrome b5 reductase participates in the ascorbate-dependent fatty acid desaturation. Three pieces of evidence are given for this statement: 1) Comparison of the rate of ascorbate-dependent oleate formation with the rate of reduction of cytochrome b5 in microsomes and in the isolated detergent form shows that only the enzymatic reduction of cytochrome b5 is fast enough to support oleate formation; 2) added enriched ascorbate-cytochrome b5 reductase increases the rate of return of stearoyl-CoA oxidised cytochrome b5 back to the reduced state; 3) addition of enriched ascorbate-cytochrome b5 reductase increases the rate of ascorbate-dependent oleate formation in rat liver microsomes."}
{"id": "PMID:215501", "title": "Increase of the gluconeogenic and decrease of the glycolytic capacity of rat liver with a change of the metabolic zonation after partial hepatectomy.", "content": "During the first 72 h after 67% partial hepatectomy of female Wistar rats (160 g) the specific activities [mumol X min-1 X (g liver)-1] of the glucogenic glucose-6-phosphatase and fructose-bisphosphatase and of the glycolytic hexokinase and 6-phosphofructokinase remained essentially constant. However, the activity of the glycolytic pyruvate kinase (L- plus M2-type) was decreased slightly and that of glucokinase was decreased markedly to below 30%, while the glucogenic phosphoenolpyruvate carboxykinase was increased to over 200%. Between 10 and 40 h after partial hepatectomy, when the proliferation started in the periportal area, a shift of the glucogenic glucose-6-phosphatase-rich zone from its normal periportal to an intermediate or even perivenous position was observed histochemically. After 48 h, when the proliferation was no longer restricted to the periportal zone, the normal glucose-6-phosphatase zonation (as before partial hepatectomy) was restored. Glycogen was degraded rapidly during the first 4 h after operation; it was later repeatedly resynthesized and degraded in correlation with the feeding rhythm of the animals. The zonation of glycogen metabolism was in accord with the observed zonation of glucose-6-phosphatase.", "contents": "Increase of the gluconeogenic and decrease of the glycolytic capacity of rat liver with a change of the metabolic zonation after partial hepatectomy. During the first 72 h after 67% partial hepatectomy of female Wistar rats (160 g) the specific activities [mumol X min-1 X (g liver)-1] of the glucogenic glucose-6-phosphatase and fructose-bisphosphatase and of the glycolytic hexokinase and 6-phosphofructokinase remained essentially constant. However, the activity of the glycolytic pyruvate kinase (L- plus M2-type) was decreased slightly and that of glucokinase was decreased markedly to below 30%, while the glucogenic phosphoenolpyruvate carboxykinase was increased to over 200%. Between 10 and 40 h after partial hepatectomy, when the proliferation started in the periportal area, a shift of the glucogenic glucose-6-phosphatase-rich zone from its normal periportal to an intermediate or even perivenous position was observed histochemically. After 48 h, when the proliferation was no longer restricted to the periportal zone, the normal glucose-6-phosphatase zonation (as before partial hepatectomy) was restored. Glycogen was degraded rapidly during the first 4 h after operation; it was later repeatedly resynthesized and degraded in correlation with the feeding rhythm of the animals. The zonation of glycogen metabolism was in accord with the observed zonation of glucose-6-phosphatase."}
{"id": "PMID:215502", "title": "Morphology and immunohistochemically-defined endocrine function of pancreatic islet cell tumours.", "content": "Thirty pancreatic islet cell tumours were histologically classified and analysed for their possible peptide hormone content using the immunohistoperoxidase method. Seven tumours contained insulin, six tumours contained gastrin and eight tumours contained glucagon. One tumour contained all three hormones. In the insulin and gastrin-containing tumours, the cells were usually arranged in solid nests of cells, with tubular and acinar formations in about half the cases. In the glucagon-containing tumours the cells were mainly arranged in anastomosing ribbons consisting of one of two layers of small cells. Most of the hormone-containing tumours were argyrophilic using Grimelius' silver reaction. All but one of the glucagon-containing tumours were incidental findings at autopsy. About half of the other tumours had metastasized. It is concluded that a relation exists between the histological pattern of growth and immunohistochemically defined endocrine function of pancreatic islet cell tumours.", "contents": "Morphology and immunohistochemically-defined endocrine function of pancreatic islet cell tumours. Thirty pancreatic islet cell tumours were histologically classified and analysed for their possible peptide hormone content using the immunohistoperoxidase method. Seven tumours contained insulin, six tumours contained gastrin and eight tumours contained glucagon. One tumour contained all three hormones. In the insulin and gastrin-containing tumours, the cells were usually arranged in solid nests of cells, with tubular and acinar formations in about half the cases. In the glucagon-containing tumours the cells were mainly arranged in anastomosing ribbons consisting of one of two layers of small cells. Most of the hormone-containing tumours were argyrophilic using Grimelius' silver reaction. All but one of the glucagon-containing tumours were incidental findings at autopsy. About half of the other tumours had metastasized. It is concluded that a relation exists between the histological pattern of growth and immunohistochemically defined endocrine function of pancreatic islet cell tumours."}
{"id": "PMID:215505", "title": "ELISA: enzyme-linked immunosorbent assay.", "content": "Similar in design to radioimmunoassay, comparable in sensitivity and specificity but easier, safer, and less expensive, this new diagnostic technique uses enzyme-labeled rather than isotope-labeled reagents. The end point is a color change that can be assessed by colorimetry or with the naked eye. Various techniques of ELISA are described, along with examples of current and potential clinical applications.", "contents": "ELISA: enzyme-linked immunosorbent assay. Similar in design to radioimmunoassay, comparable in sensitivity and specificity but easier, safer, and less expensive, this new diagnostic technique uses enzyme-labeled rather than isotope-labeled reagents. The end point is a color change that can be assessed by colorimetry or with the naked eye. Various techniques of ELISA are described, along with examples of current and potential clinical applications."}
{"id": "PMID:215506", "title": "Ultrastructural and enzyme histochemical study of ovarian hilar cells in women and their relationships with sympathetic nerves.", "content": "The ultrastructure of normal ovarian hilar cells, both during the reproductive era and after the menopause, shows evidence of steroid hormone synthesis. In this respect these cells are very similar to Leydig cells in that they contain mitochondria with a dense matrix, a highly developed smooth endoplasmic reticulum, Reinke crystals, and microcystalline inclusions. The latter are much more numerous than in the normal testis. Their enzymatic activities are quite similar to those of Leydig cells. Ovarian hilar cells seem to originate from progressive metamorphosis of fibroblastic cells under the induction of sympathetic nervous structures. Their relations with hilar nerves are of three types: simple direct membrane contact without a Schwann cell sheath, intimate intracytoplasmic relationships, and specialized contacts, which are comparable to a synapse.", "contents": "Ultrastructural and enzyme histochemical study of ovarian hilar cells in women and their relationships with sympathetic nerves. The ultrastructure of normal ovarian hilar cells, both during the reproductive era and after the menopause, shows evidence of steroid hormone synthesis. In this respect these cells are very similar to Leydig cells in that they contain mitochondria with a dense matrix, a highly developed smooth endoplasmic reticulum, Reinke crystals, and microcystalline inclusions. The latter are much more numerous than in the normal testis. Their enzymatic activities are quite similar to those of Leydig cells. Ovarian hilar cells seem to originate from progressive metamorphosis of fibroblastic cells under the induction of sympathetic nervous structures. Their relations with hilar nerves are of three types: simple direct membrane contact without a Schwann cell sheath, intimate intracytoplasmic relationships, and specialized contacts, which are comparable to a synapse."}
{"id": "PMID:215507", "title": "Genetic studies on the Gc subtypes.", "content": "Gc subtypes were determined by immunofixation isoelectric focusing. In a family study involving 93 families with a total of 176 children, a three-allele model with six genotypes was confirmed. The distribution of Gc subtypes was studied in three populations from Europe and in a sample of Druzes from Northern Israel. Three new variant Gc types were observed.", "contents": "Genetic studies on the Gc subtypes. Gc subtypes were determined by immunofixation isoelectric focusing. In a family study involving 93 families with a total of 176 children, a three-allele model with six genotypes was confirmed. The distribution of Gc subtypes was studied in three populations from Europe and in a sample of Druzes from Northern Israel. Three new variant Gc types were observed."}
{"id": "PMID:215508", "title": "Localization of a gene for human alpha-galactosidase B (= n-acetyl-alpha-d-galactosaminidase) on chromosome 22.", "content": "The localization of the structural gene for human alpha-galactosidase B (= N-acetyl-alpha-galactosaminidase) was investigated by means of man-Chinese hamster and man-mouse somatic cell hybrids. The hybrid clones were analyzed for chromosomes and for a large number of known enzyme markers. The lysates of the hybrid cells were treated with Sepharose-coupled antihuman alpha-galactosidase B and the activity of the adsorbed enzyme was measured on the Sepharose beads as N-acetyl-alpha-galactosaminidase. The results show that the structural gene for human alpha-galactosidase B is situated on chromosome 22, and that there is no structural relationship between human alpha-galactosidase A and human alpha-galactosidase B.", "contents": "Localization of a gene for human alpha-galactosidase B (= n-acetyl-alpha-d-galactosaminidase) on chromosome 22. The localization of the structural gene for human alpha-galactosidase B (= N-acetyl-alpha-galactosaminidase) was investigated by means of man-Chinese hamster and man-mouse somatic cell hybrids. The hybrid clones were analyzed for chromosomes and for a large number of known enzyme markers. The lysates of the hybrid cells were treated with Sepharose-coupled antihuman alpha-galactosidase B and the activity of the adsorbed enzyme was measured on the Sepharose beads as N-acetyl-alpha-galactosaminidase. The results show that the structural gene for human alpha-galactosidase B is situated on chromosome 22, and that there is no structural relationship between human alpha-galactosidase A and human alpha-galactosidase B."}
{"id": "PMID:215511", "title": "Histological types of nasopharyngeal carcinoma in an intermediate risk area.", "content": "Between April and December 1974, 485 cases of NPC were seen at the Salah Aza\u00efz Institute in Tunis. A histological study was carried out according to a classification that comprises four types of tumour:well-differentiated squamous-cell carcinoma, poorly-differentiated squamous-cell carcinoma, 'nasopharyngeal' type carcinoma and an anaplastic type. Some correlation between these histological types and clinical, epidemiological, virological and prognostic features was found.", "contents": "Histological types of nasopharyngeal carcinoma in an intermediate risk area. Between April and December 1974, 485 cases of NPC were seen at the Salah Aza\u00efz Institute in Tunis. A histological study was carried out according to a classification that comprises four types of tumour:well-differentiated squamous-cell carcinoma, poorly-differentiated squamous-cell carcinoma, 'nasopharyngeal' type carcinoma and an anaplastic type. Some correlation between these histological types and clinical, epidemiological, virological and prognostic features was found."}
{"id": "PMID:215513", "title": "Analytical aspects of symptoms of nasopharyngeal malignancies.", "content": "The various symptoms of 766 patients with nasopharyngeal malignancies (641 carcinomas and 125 malignant lymphomas, confirmed histologically) were analysed statistically from the viewpoint of early diagnosis. These can be divided into aural, nasal, pharyngeal, ophthalmic, cervical lymph node and cranial nerve symptoms. The frequencies of these symptoms were compared in patients with tumours of different histopathological classifications: the nasopharyngeal malignancies were divided into carcinoma and malignant lymphoma, and the carcinomas were subclassified according to their degree of differentiation. On the whole, lymphoma patients more often had nasal and pharyngeal symptoms, and carcinoma patients ophthalmic and cranial nerve symptoms. It is considered that this difference is due to the different ways in which the two kinds of tumour develop. The frequencies of the symptoms naturally increased with the clinical course of the disease; the frequencies of the symptom both as an initial sign and as observed during the clinical course of the disease were examined. Nasopharyngeal malignancies are not indicated by localized symptoms but become evident when adjoining organs, such as the ear or nose, give some sign of abnormality. In not a few cases, a neck swelling is the initial sign; and in some patients, cranial nerve involvement is the first symptom. Since a patient may not understand the significance of his symptom and may consult a general surgeon, physician, ophthalmologist and/or paediatrician, these specialists should be alerted to the recognition of this disease.", "contents": "Analytical aspects of symptoms of nasopharyngeal malignancies. The various symptoms of 766 patients with nasopharyngeal malignancies (641 carcinomas and 125 malignant lymphomas, confirmed histologically) were analysed statistically from the viewpoint of early diagnosis. These can be divided into aural, nasal, pharyngeal, ophthalmic, cervical lymph node and cranial nerve symptoms. The frequencies of these symptoms were compared in patients with tumours of different histopathological classifications: the nasopharyngeal malignancies were divided into carcinoma and malignant lymphoma, and the carcinomas were subclassified according to their degree of differentiation. On the whole, lymphoma patients more often had nasal and pharyngeal symptoms, and carcinoma patients ophthalmic and cranial nerve symptoms. It is considered that this difference is due to the different ways in which the two kinds of tumour develop. The frequencies of the symptoms naturally increased with the clinical course of the disease; the frequencies of the symptom both as an initial sign and as observed during the clinical course of the disease were examined. Nasopharyngeal malignancies are not indicated by localized symptoms but become evident when adjoining organs, such as the ear or nose, give some sign of abnormality. In not a few cases, a neck swelling is the initial sign; and in some patients, cranial nerve involvement is the first symptom. Since a patient may not understand the significance of his symptom and may consult a general surgeon, physician, ophthalmologist and/or paediatrician, these specialists should be alerted to the recognition of this disease."}
{"id": "PMID:215514", "title": "Descriptive and analytical epidemiology of nasopharyngeal cancer.", "content": "Information concerning the descriptive and analytical epidemiology of NPC that has been reported mainly since the first international symposium on the subject in Singapore in 1964 are reviewed. NPC is rare in most countries in the world, with an age-adjusted incidence rate of less than 1 per 100,000, and the incidence rate is twice as high in males as in females. Chinese of southern origin have a uniquely high risk, the incidence rates per 100,000 being 10--20 in males and 5--10 in females. The greater the admixture of southern Chinese blood in a given ethnic group, the more likely it is that the NPC incidence rate in that group will be raised. The incidence in both sexes begins to rise after the ages of 20--24 and reaches a plateau at between 45 and 54. When the logarithm of mortality and morbidity is plotted against the logarithm of the age, the power of the age that provides the best fit to a straight line on a log-log graph is approximately two to four. These figures are lower than for other cancers. Seroepidemiological case-control studies indicate that both different birthplace and abnormal response to EBV antigen significantly enhance the risk for NPC; when these two factors are combined, the relative risk appears to rise further. The effect of other environmental chemicals, such as from cigarette smoking, shown to be significant in several retrospective studies, could explain in part epidemiological phenomena such as sex difference in incidence. The definitive reason for the uniquely high risk in southern Chinese should be further investigated by taking into account the interactions of host factors (birthplace, HLA, etc.) and environmental factors (EBV, chemical carcinogens including nitrosamines, excessive intake of salted fish, nutritional deficiencies, etc.).", "contents": "Descriptive and analytical epidemiology of nasopharyngeal cancer. Information concerning the descriptive and analytical epidemiology of NPC that has been reported mainly since the first international symposium on the subject in Singapore in 1964 are reviewed. NPC is rare in most countries in the world, with an age-adjusted incidence rate of less than 1 per 100,000, and the incidence rate is twice as high in males as in females. Chinese of southern origin have a uniquely high risk, the incidence rates per 100,000 being 10--20 in males and 5--10 in females. The greater the admixture of southern Chinese blood in a given ethnic group, the more likely it is that the NPC incidence rate in that group will be raised. The incidence in both sexes begins to rise after the ages of 20--24 and reaches a plateau at between 45 and 54. When the logarithm of mortality and morbidity is plotted against the logarithm of the age, the power of the age that provides the best fit to a straight line on a log-log graph is approximately two to four. These figures are lower than for other cancers. Seroepidemiological case-control studies indicate that both different birthplace and abnormal response to EBV antigen significantly enhance the risk for NPC; when these two factors are combined, the relative risk appears to rise further. The effect of other environmental chemicals, such as from cigarette smoking, shown to be significant in several retrospective studies, could explain in part epidemiological phenomena such as sex difference in incidence. The definitive reason for the uniquely high risk in southern Chinese should be further investigated by taking into account the interactions of host factors (birthplace, HLA, etc.) and environmental factors (EBV, chemical carcinogens including nitrosamines, excessive intake of salted fish, nutritional deficiencies, etc.)."}
{"id": "PMID:215515", "title": "Histopathological types of nasopharyngeal carcinoma in a low-risk area: Japan.", "content": "NPC in Japan was studied histopathologically by examining 816 NPCs from among 3 338 biopsies from patients with tumours of the nasopharynx and other parts of the upper respiratory system. In addition, a comparative study on NPC among Taiwanese and an immunoserological study were carried out. When comparing histological types of malignant tumours of the upper respiratory tract, poorly-differentiated squamous-cell carcinoma predominated only in those of the nasopharynx. Malignant nasopharyngeal tumours in Japanese patients were characterized by two histological features: predominance of squamous-cell carcinoma, especially of the poorly-differentiated type, and a relatively high frequenty of malignant lymphoma. An analysis of 731 cases of NPC showed that a vast majority (86.7%) were poorly-differentiated and a minority (13.3%) well-differentiated squamous-cell carcinomas. The former included 45.8% spindle-polygonal-cell carcinomas, 26.6% transitional-cell carcinomas ana 14.3% lymphoepitheliomas. Although the transitional-cell carcinomas and lymphoepitheliomas showed a peculiar morphology, it was confirmed that they are of a squamous nature. A comparative study of the histology of NPCs in a high-risk area, Taiwan, and in a low-risk area, Japan, revealed considerable differences between the two groups. Well-differentiated carcinomas were infrequent in both groups but were more frequent in Japanese than in Taiwanese, while the frequency of poorly-differentiated carcinomas, especially transitional-cell carcinomas and lymphoepitheliomas, was much higher among Taiwanese. A seroepidemiological study on the relation of anti-VCA antibody titres to histological type of tumour in 84 Japanese NPC patients revealed that the rate of positivity and the geometric mean of the titres were considerably higher in patients with lymphoepitheliomas. Althougropathological study along this line would appear to be important, since the results obtained in Japanese NPC cases may suggest that EBV genomes in NPC cells vary with the grade of differentiation of NPC.", "contents": "Histopathological types of nasopharyngeal carcinoma in a low-risk area: Japan. NPC in Japan was studied histopathologically by examining 816 NPCs from among 3 338 biopsies from patients with tumours of the nasopharynx and other parts of the upper respiratory system. In addition, a comparative study on NPC among Taiwanese and an immunoserological study were carried out. When comparing histological types of malignant tumours of the upper respiratory tract, poorly-differentiated squamous-cell carcinoma predominated only in those of the nasopharynx. Malignant nasopharyngeal tumours in Japanese patients were characterized by two histological features: predominance of squamous-cell carcinoma, especially of the poorly-differentiated type, and a relatively high frequenty of malignant lymphoma. An analysis of 731 cases of NPC showed that a vast majority (86.7%) were poorly-differentiated and a minority (13.3%) well-differentiated squamous-cell carcinomas. The former included 45.8% spindle-polygonal-cell carcinomas, 26.6% transitional-cell carcinomas ana 14.3% lymphoepitheliomas. Although the transitional-cell carcinomas and lymphoepitheliomas showed a peculiar morphology, it was confirmed that they are of a squamous nature. A comparative study of the histology of NPCs in a high-risk area, Taiwan, and in a low-risk area, Japan, revealed considerable differences between the two groups. Well-differentiated carcinomas were infrequent in both groups but were more frequent in Japanese than in Taiwanese, while the frequency of poorly-differentiated carcinomas, especially transitional-cell carcinomas and lymphoepitheliomas, was much higher among Taiwanese. A seroepidemiological study on the relation of anti-VCA antibody titres to histological type of tumour in 84 Japanese NPC patients revealed that the rate of positivity and the geometric mean of the titres were considerably higher in patients with lymphoepitheliomas. Althougropathological study along this line would appear to be important, since the results obtained in Japanese NPC cases may suggest that EBV genomes in NPC cells vary with the grade of differentiation of NPC."}
{"id": "PMID:215516", "title": "Histological typing of nasopharyngeal carcinoma.", "content": "There is little agreement about correlations between histological type and the epidemiological and biological characteristics of NPC. This is largely due to variations in terminology and diagnostic criteria. The use of the terminology and definitions proposed by WHO would facilitate and improve international comparisons.", "contents": "Histological typing of nasopharyngeal carcinoma. There is little agreement about correlations between histological type and the epidemiological and biological characteristics of NPC. This is largely due to variations in terminology and diagnostic criteria. The use of the terminology and definitions proposed by WHO would facilitate and improve international comparisons."}
{"id": "PMID:215518", "title": "Morphological transformation of nasopharyngeal epithelial cells in vitro by Epstein-Barr virus from B95-8 cells.", "content": "Tissue fragments of fresh biopsy specimens from the non-neoplastic NP mucosa of 20 subjects, from the tumours of 10 NPC patients, from the mucosa of freshly removed tonsils from nine subjects and from the primary lesions of seven patients with malignancies of the upper respiratory or alimentary tract other than NPC were infected with EBV derived from B95-8 cells. A significantly higher frequency of growth stimulation and a greater mean growth ratio between infected and uninfected fragments from the same source were observed in the non-neoplastic NP mucosa specimens than in the others. In addition, the growth characteristics and the morphology of the cells in the infected non-neoplastic NP mucosal explants resembled those of transformed cells; but whether they possess malignant potential is being investigated.", "contents": "Morphological transformation of nasopharyngeal epithelial cells in vitro by Epstein-Barr virus from B95-8 cells. Tissue fragments of fresh biopsy specimens from the non-neoplastic NP mucosa of 20 subjects, from the tumours of 10 NPC patients, from the mucosa of freshly removed tonsils from nine subjects and from the primary lesions of seven patients with malignancies of the upper respiratory or alimentary tract other than NPC were infected with EBV derived from B95-8 cells. A significantly higher frequency of growth stimulation and a greater mean growth ratio between infected and uninfected fragments from the same source were observed in the non-neoplastic NP mucosa specimens than in the others. In addition, the growth characteristics and the morphology of the cells in the infected non-neoplastic NP mucosal explants resembled those of transformed cells; but whether they possess malignant potential is being investigated."}
{"id": "PMID:215520", "title": "Epstein-Barr virus-epithelial cell interaction and its implication in the etiology of nasopharyngeal carcinoma.", "content": "The etiological role of EBV in NPC is still a matter for debate. A major question is how the viral DNA becomes associated with the carcinoma cell, since only B lymphocytes are at present known to have receptors to EBV. The following hypotheses are proposed: (1) The epithelial cells of the nasopharynx have EBV receptors in vivo; transformation of the epithelial cell thus results from a direct interaction between EBV and this cell type. The epithelial cells of the nasopharynx are not permissive for EBV infection. In this case: (2) Malignant or premalignant changes in the epithelial cells are required for EBV infection to take place. Thus, EBV may act either as a passive passenger or as an active promoter in NPC development. Or, (3) infection of the epithelial cells results from a specific interaction (involving either transfection or hybrid formation) between an EBV-infected B lymphocyte and an epithelial cell within the nasopharynx. Here again, the virus may either be passive or act as an oncogenic factor. Recent data are presented both for and against these hypotheses.", "contents": "Epstein-Barr virus-epithelial cell interaction and its implication in the etiology of nasopharyngeal carcinoma. The etiological role of EBV in NPC is still a matter for debate. A major question is how the viral DNA becomes associated with the carcinoma cell, since only B lymphocytes are at present known to have receptors to EBV. The following hypotheses are proposed: (1) The epithelial cells of the nasopharynx have EBV receptors in vivo; transformation of the epithelial cell thus results from a direct interaction between EBV and this cell type. The epithelial cells of the nasopharynx are not permissive for EBV infection. In this case: (2) Malignant or premalignant changes in the epithelial cells are required for EBV infection to take place. Thus, EBV may act either as a passive passenger or as an active promoter in NPC development. Or, (3) infection of the epithelial cells results from a specific interaction (involving either transfection or hybrid formation) between an EBV-infected B lymphocyte and an epithelial cell within the nasopharynx. Here again, the virus may either be passive or act as an oncogenic factor. Recent data are presented both for and against these hypotheses."}
{"id": "PMID:215521", "title": "Early and late components of Epstein-Barr virus-associated membrane antigen in superinfected Daudi cells and their reactivity with sera from nasopharyngeal carcinoma patients.", "content": "Investigations were carried out on newly synthesized MA, VCA and EA in Daudi cells superinfected with the P3HR-1 strain of EBV and treated with trypsin to remove previously adsorbed MA-positive material from the cell surface. Synthesis of MA, VCA and EA was completely blocked by puromycin. A marked reduction in the frequency of MA-positive cells was observed in the infected cell cultures in the presence of either Ara-C or PA, but a fraction of the MA-positive cells was insensitive to the inhibitors. Differential absorption of an EBV antibody-positive human serum with Ara-C-treated or -untreated infected cells revealed two antigenically different components of MA: early (Ara-C-insensitive) and late (Ara-C-sensitive) MA. Three of five sera from patients with NPC, but none of five sera from normal adults, showed an apparent 'prozone' phenomenon in their reactivity against late but not early MA.", "contents": "Early and late components of Epstein-Barr virus-associated membrane antigen in superinfected Daudi cells and their reactivity with sera from nasopharyngeal carcinoma patients. Investigations were carried out on newly synthesized MA, VCA and EA in Daudi cells superinfected with the P3HR-1 strain of EBV and treated with trypsin to remove previously adsorbed MA-positive material from the cell surface. Synthesis of MA, VCA and EA was completely blocked by puromycin. A marked reduction in the frequency of MA-positive cells was observed in the infected cell cultures in the presence of either Ara-C or PA, but a fraction of the MA-positive cells was insensitive to the inhibitors. Differential absorption of an EBV antibody-positive human serum with Ara-C-treated or -untreated infected cells revealed two antigenically different components of MA: early (Ara-C-insensitive) and late (Ara-C-sensitive) MA. Three of five sera from patients with NPC, but none of five sera from normal adults, showed an apparent 'prozone' phenomenon in their reactivity against late but not early MA."}
{"id": "PMID:215522", "title": "Heterogeneity of Epstein-Barr virus derived from P3HR-1 cells.", "content": "Infection of cells of the EBV-free human B-lymphoma lines BJAB and Ramos resulted in conversion of these cells to EBV-genome carriers expressing EBNA. EBV isolates from P3HR-1 cells induced a heterogeneous EBNA pattern: both a faintly granular pattern and brilliant EBNA-expression were observed. The two types of EBNA-expressing cells could be separated upon cloning. Brilliantly EBNA-expressing cells always segregated varying percentages of EBNA-negative cells. An EBNA-negative subclone derived from these cells was devoid of detectable EBV DNA. Nucleic acid hybridization experiments failed to reveal a correlation between the intensity of EBNA expression and the number of EBV genome equivalents per cell. EBV genome-containing cells had an average of 14-fold more cells showing EA synthesis after superinfection by P3HR-1 virus, when compared with EBNA-negative cells infected under identical conditions. Studies on the kinetics of EA induction in EBNA-positive and EBNA-negative cells indicate that complementation is required for the induction of EA after superinfection.", "contents": "Heterogeneity of Epstein-Barr virus derived from P3HR-1 cells. Infection of cells of the EBV-free human B-lymphoma lines BJAB and Ramos resulted in conversion of these cells to EBV-genome carriers expressing EBNA. EBV isolates from P3HR-1 cells induced a heterogeneous EBNA pattern: both a faintly granular pattern and brilliant EBNA-expression were observed. The two types of EBNA-expressing cells could be separated upon cloning. Brilliantly EBNA-expressing cells always segregated varying percentages of EBNA-negative cells. An EBNA-negative subclone derived from these cells was devoid of detectable EBV DNA. Nucleic acid hybridization experiments failed to reveal a correlation between the intensity of EBNA expression and the number of EBV genome equivalents per cell. EBV genome-containing cells had an average of 14-fold more cells showing EA synthesis after superinfection by P3HR-1 virus, when compared with EBNA-negative cells infected under identical conditions. Studies on the kinetics of EA induction in EBNA-positive and EBNA-negative cells indicate that complementation is required for the induction of EA after superinfection."}
{"id": "PMID:215523", "title": "Expression of latent Epstein-Barr virus genomes in human epithelial/Burkitt's lymphoblastoid hybrid cells.", "content": "Expression of latent Epstein-Barr virus genomes in somatic-cell hybrids of Burkitt's lymphoblastoid cells has been studied. Treatment of the hybrid cells, D98/Raji and D98/HR-1, with IUDR induced the formation of EA and VCA and replication of virus DNA, whereas the same treatment of Raji cells induced only the formation of EA. The patterns of transcription of virus genomes in these three cell lines were, however, very similar: 25% without treatment with IUDR, 30% immediately after the treatment and 50% (entire genome transcription) three days after being transferred to fresh medium. The amount of virus RNA in the cells, calculated from DNA-RNA hybridization kinetics, was proportional to the number of virus genomes per cell, suggesting that every copy of virus DNA in these cells is actively transcribed.", "contents": "Expression of latent Epstein-Barr virus genomes in human epithelial/Burkitt's lymphoblastoid hybrid cells. Expression of latent Epstein-Barr virus genomes in somatic-cell hybrids of Burkitt's lymphoblastoid cells has been studied. Treatment of the hybrid cells, D98/Raji and D98/HR-1, with IUDR induced the formation of EA and VCA and replication of virus DNA, whereas the same treatment of Raji cells induced only the formation of EA. The patterns of transcription of virus genomes in these three cell lines were, however, very similar: 25% without treatment with IUDR, 30% immediately after the treatment and 50% (entire genome transcription) three days after being transferred to fresh medium. The amount of virus RNA in the cells, calculated from DNA-RNA hybridization kinetics, was proportional to the number of virus genomes per cell, suggesting that every copy of virus DNA in these cells is actively transcribed."}
{"id": "PMID:215524", "title": "Interaction between Epstein-Barr virus and type-C virus in human cells.", "content": "The interaction between EBV and type-C viruses was studied in our FVNC experimental system, in which EBV and type-C viral genomes are contained in each cell. The data indicate that the human lymphoid FVNC cells are sensitive to both EBV and type-C virus exposure, showing high frequencies of induction of both repressed viral genomes. The two different viral genomes may be associated with different chromosomes in individual cells.", "contents": "Interaction between Epstein-Barr virus and type-C virus in human cells. The interaction between EBV and type-C viruses was studied in our FVNC experimental system, in which EBV and type-C viral genomes are contained in each cell. The data indicate that the human lymphoid FVNC cells are sensitive to both EBV and type-C virus exposure, showing high frequencies of induction of both repressed viral genomes. The two different viral genomes may be associated with different chromosomes in individual cells."}
{"id": "PMID:215526", "title": "Clinical evaluation of EBV serology in American patients with nasopharyngeal carcinoma.", "content": "There is now extensive immunological, biological and biochemical evidence to support a possible etiological relationship between EBV and NPC in patients from different geographical locations. Besides providing information on the question of etiology, the results from immunological investigations suggest that antibodies to some of the EBV-associated antigens might also be of clinical importance in the diagnosis and prognosis of NPC. To determine the possible clinical application of EBV serology to American NPC, sera from patients seen at the Mayo Clinic and the National Institutes of Health were examined for antibodies to EBV-associated antigens in an effort to identify those parameters which most reliably distinguish NPC from other types of cancer. The results show that high antibody titres to EBV-induced EA and the presence of antibody to EBV antigens in the IgA immunoglobulin fraction were the two most specific discriminating parameters, although neither was infallible. These findings are discussed in relation to future studies that are needed in order to determine the potential clinical value of EBV serology to the diagnosis and prognosis of NPC.", "contents": "Clinical evaluation of EBV serology in American patients with nasopharyngeal carcinoma. There is now extensive immunological, biological and biochemical evidence to support a possible etiological relationship between EBV and NPC in patients from different geographical locations. Besides providing information on the question of etiology, the results from immunological investigations suggest that antibodies to some of the EBV-associated antigens might also be of clinical importance in the diagnosis and prognosis of NPC. To determine the possible clinical application of EBV serology to American NPC, sera from patients seen at the Mayo Clinic and the National Institutes of Health were examined for antibodies to EBV-associated antigens in an effort to identify those parameters which most reliably distinguish NPC from other types of cancer. The results show that high antibody titres to EBV-induced EA and the presence of antibody to EBV antigens in the IgA immunoglobulin fraction were the two most specific discriminating parameters, although neither was infallible. These findings are discussed in relation to future studies that are needed in order to determine the potential clinical value of EBV serology to the diagnosis and prognosis of NPC."}
{"id": "PMID:215529", "title": "Differences in EBV antibody titres of patients with nasopharyngeal carcinoma originating from high, intermediate and low incidence areas.", "content": "In order to assess the differences in serological reactivities of NPC patients from high, intermediate and low incidence areas, 288 NPC sera from Hong Kong, Singapore, Tunis, East Africa, Paris and Los Angeles, together with sera from patients with ear, nose and throat tumours other than NPC and with those from normal individuals from the same areas, were tested 'blind' with the same batches of antigen. Important differences (up to 3-fold) in the GMTs of antibodies directed against VCA, EA and EBNA were observed between different ethnic groups. Although the stages of the disease varied somewhat between groups, the main cause of the variations appeared to lie in the socio-economic environment of the patients. Apart from these variations, and regardless of geographical or ethnic origins, NPC was consistently found to be associated with an active infection (or reactivation) by Epstein-Barr virus, which was not the case for patients with other tumours or for normal individuals from the same areas or of the same ethnic groups.", "contents": "Differences in EBV antibody titres of patients with nasopharyngeal carcinoma originating from high, intermediate and low incidence areas. In order to assess the differences in serological reactivities of NPC patients from high, intermediate and low incidence areas, 288 NPC sera from Hong Kong, Singapore, Tunis, East Africa, Paris and Los Angeles, together with sera from patients with ear, nose and throat tumours other than NPC and with those from normal individuals from the same areas, were tested 'blind' with the same batches of antigen. Important differences (up to 3-fold) in the GMTs of antibodies directed against VCA, EA and EBNA were observed between different ethnic groups. Although the stages of the disease varied somewhat between groups, the main cause of the variations appeared to lie in the socio-economic environment of the patients. Apart from these variations, and regardless of geographical or ethnic origins, NPC was consistently found to be associated with an active infection (or reactivation) by Epstein-Barr virus, which was not the case for patients with other tumours or for normal individuals from the same areas or of the same ethnic groups."}
{"id": "PMID:215530", "title": "Cell-mediated immunity, Epstein-Barr virus and nasopharyngeal carcinoma.", "content": "Cellular immunity is apparently important in host defenses against cancer. A growing body of information on CMI to EBV is here reviewed, providing a strong basis for studies of such reactivity in NPC. Present work suggests that CMI responses to virus- and tumour-associated antigens may have implications for etiology, diagnosis and treatment.", "contents": "Cell-mediated immunity, Epstein-Barr virus and nasopharyngeal carcinoma. Cellular immunity is apparently important in host defenses against cancer. A growing body of information on CMI to EBV is here reviewed, providing a strong basis for studies of such reactivity in NPC. Present work suggests that CMI responses to virus- and tumour-associated antigens may have implications for etiology, diagnosis and treatment."}
{"id": "PMID:215531", "title": "General immunological status of nasopharyngeal carcinoma patients in Singapore.", "content": "Newly diagnosed NPC patients were found to have impaired general T-cell functions, as determined in vivo by the Mantoux test and in vitro by the PHA response assay. Treated remission patients were as hyporesponsiveness as newly diagnosed patients. PHA hyporesponsiveness was associated with the HLA profile of A2-B Sin 2 and with high antibody titres to EBV-related antigens, in particular to the early antigen. Impaired responses in the Mantoux or PHA tests were associated with poor survival. The impaired response could be partially or totally restored by in vitro treatment of the hyporesponsive lymphocytes with levamisole.", "contents": "General immunological status of nasopharyngeal carcinoma patients in Singapore. Newly diagnosed NPC patients were found to have impaired general T-cell functions, as determined in vivo by the Mantoux test and in vitro by the PHA response assay. Treated remission patients were as hyporesponsiveness as newly diagnosed patients. PHA hyporesponsiveness was associated with the HLA profile of A2-B Sin 2 and with high antibody titres to EBV-related antigens, in particular to the early antigen. Impaired responses in the Mantoux or PHA tests were associated with poor survival. The impaired response could be partially or totally restored by in vitro treatment of the hyporesponsive lymphocytes with levamisole."}
{"id": "PMID:215532", "title": "Autoantibodies (cold lymphocytotoxins, antiactin antibodies and antinuclear factors) in nasopharyngeal carcinoma patients.", "content": "LTA, SMA and ANA were found at higher frequencies in sera from NPC patients than in those from matched controls. The frequency and GMTs of LTA-positive sera varied with the origin of the patient (Chinese greater than North African greater than Caucasian, thus paralleling the risk for NPC in each ethnic group) and the stage of the disease (stage IV greater than stage I). A positive correlation was found between LTA and anti-EBV titres with regard to anti-VCA and anti-EBNA antibodies. SMA were specific for actin, and their titres did not correlate with anti-EBV (VCA, EBNA and EA) titres. Although there was no evidence for an abnormal immunogenicity of the self components recognized by the three autoantibodies, their independent augmentations did not favour the alternative hypothesis of a common central mechanism for their production. The origin and the biological significance of these autoantibodies remains, therefore, to be explained.", "contents": "Autoantibodies (cold lymphocytotoxins, antiactin antibodies and antinuclear factors) in nasopharyngeal carcinoma patients. LTA, SMA and ANA were found at higher frequencies in sera from NPC patients than in those from matched controls. The frequency and GMTs of LTA-positive sera varied with the origin of the patient (Chinese greater than North African greater than Caucasian, thus paralleling the risk for NPC in each ethnic group) and the stage of the disease (stage IV greater than stage I). A positive correlation was found between LTA and anti-EBV titres with regard to anti-VCA and anti-EBNA antibodies. SMA were specific for actin, and their titres did not correlate with anti-EBV (VCA, EBNA and EA) titres. Although there was no evidence for an abnormal immunogenicity of the self components recognized by the three autoantibodies, their independent augmentations did not favour the alternative hypothesis of a common central mechanism for their production. The origin and the biological significance of these autoantibodies remains, therefore, to be explained."}
{"id": "PMID:215533", "title": "In vivo cell-mediated immunity in Chinese patients with nasopharyngeal carcinoma.", "content": "Delayed hypersensitivity to antigens derived from four EBV-related (KHLY 28, Raji, F265 and NC37) and one EBV-unrelated (Molt) T-lymphoid cell lines and to standard antigens (Trichophyton, Candida albicans and streptokinase/streptodornase) was measured in 104 NPC patients and 24 patients with other cancers. Of the NPC patients with non-disseminated disease, 55/86 (63.2%) had a positive skin reaction to HKLY 28 extract, compared with only 1/18 (5.6%) OC patients with non-disseminated disease. The frequencies of these NPC patients with positive skin reactions to the other cell-line extracts were significantly lower (1.7-5.4%). From the preliminary results of a longitudinal study, skin testing with this particular crude membrane extract from HKLY 28 cells appears to be of little practical value in monitoring the clinical evolution of NPC, although a significant association between clinical evolution and certain patterns of skin reactivity response to the extract was found in about two-thirds of the cases analysed.", "contents": "In vivo cell-mediated immunity in Chinese patients with nasopharyngeal carcinoma. Delayed hypersensitivity to antigens derived from four EBV-related (KHLY 28, Raji, F265 and NC37) and one EBV-unrelated (Molt) T-lymphoid cell lines and to standard antigens (Trichophyton, Candida albicans and streptokinase/streptodornase) was measured in 104 NPC patients and 24 patients with other cancers. Of the NPC patients with non-disseminated disease, 55/86 (63.2%) had a positive skin reaction to HKLY 28 extract, compared with only 1/18 (5.6%) OC patients with non-disseminated disease. The frequencies of these NPC patients with positive skin reactions to the other cell-line extracts were significantly lower (1.7-5.4%). From the preliminary results of a longitudinal study, skin testing with this particular crude membrane extract from HKLY 28 cells appears to be of little practical value in monitoring the clinical evolution of NPC, although a significant association between clinical evolution and certain patterns of skin reactivity response to the extract was found in about two-thirds of the cases analysed."}
{"id": "PMID:215534", "title": "Use of immunological studies in evaluating the clinical course of nasopharyngeal carcinoma.", "content": "The prognosis of a NPC patient is influenced by many factors, including the therapeutic method used and the clinical stage and histological characteristics of the tumour. The immune response of the peripheral lymphocytes was examined in 27 patients with NPC, and it was concluded that this response accurately indicates the clinical course of the diseases as compared with clinical stage of disease, histological type of tumour and anti-VCA-antibody titre.", "contents": "Use of immunological studies in evaluating the clinical course of nasopharyngeal carcinoma. The prognosis of a NPC patient is influenced by many factors, including the therapeutic method used and the clinical stage and histological characteristics of the tumour. The immune response of the peripheral lymphocytes was examined in 27 patients with NPC, and it was concluded that this response accurately indicates the clinical course of the diseases as compared with clinical stage of disease, histological type of tumour and anti-VCA-antibody titre."}
{"id": "PMID:215538", "title": "Prolonged prostaglandin E1 stimulation of cyclic AMP production in transformed and normal WI-38 fibroblasts.", "content": "Long-term (48-hr) incubations of either the fibroblast strain WI-38 or its SV40-transformed counterpart, WI-38-VA13-2RA, in growth medium containing 1 micron prostaglandin E1 (PGE1) resulted in a sustained production and release of cyclic AMP from the cells into the medium. Despite the steady production, intracellular levels of the nucleotide decreased, reaching steady-state values within 4 hr of the initial exposure to PGE1. These values were maintained for the remainder of the 48-hr experimental period. The steady-state levels of intracellular cyclic AMP were higher than those observed in unstimulated cells, and cyclic AMP-dependent protein phosphokinase was in a highly activated state as compared to controls. Under these conditions little change in the growth or morphology of either the normal or transformed cells was observed. In contrast, inhibition of growth, apparent cell death, and unusual morphological changes were observed in both normal and transformed cells when high concentrations of either PGE1 (10 micron) or the phosphodiesterase inhibitor 1-methyl, 3-isobutylxanthine (0.5 mM to 2 mM) were used, which was indicative of toxic effects of the drugs. It was concluded that cyclic AMP-mediated activation of protein phosphokinase does not completely inhibit growth in WI-38 cells or restore normal growth and morphology to the SV40-transformed cells.", "contents": "Prolonged prostaglandin E1 stimulation of cyclic AMP production in transformed and normal WI-38 fibroblasts. Long-term (48-hr) incubations of either the fibroblast strain WI-38 or its SV40-transformed counterpart, WI-38-VA13-2RA, in growth medium containing 1 micron prostaglandin E1 (PGE1) resulted in a sustained production and release of cyclic AMP from the cells into the medium. Despite the steady production, intracellular levels of the nucleotide decreased, reaching steady-state values within 4 hr of the initial exposure to PGE1. These values were maintained for the remainder of the 48-hr experimental period. The steady-state levels of intracellular cyclic AMP were higher than those observed in unstimulated cells, and cyclic AMP-dependent protein phosphokinase was in a highly activated state as compared to controls. Under these conditions little change in the growth or morphology of either the normal or transformed cells was observed. In contrast, inhibition of growth, apparent cell death, and unusual morphological changes were observed in both normal and transformed cells when high concentrations of either PGE1 (10 micron) or the phosphodiesterase inhibitor 1-methyl, 3-isobutylxanthine (0.5 mM to 2 mM) were used, which was indicative of toxic effects of the drugs. It was concluded that cyclic AMP-mediated activation of protein phosphokinase does not completely inhibit growth in WI-38 cells or restore normal growth and morphology to the SV40-transformed cells."}
{"id": "PMID:215541", "title": "Cellular immune response to cytomegalovirus infection after renal transplantation.", "content": "A prospective study of 15 patients who received renal transplants defined the effect of renal transplantation on the cellular immune response to cytomegalovirus infection. Of 15 patients, 14 developed cytomegalovirus infection, usually in the first 2 months after transplantation, and all infections were accompanied by a normal humoral immune response. After the initiation of immunosuppressive therapy and transplantation, there was a general depression of lymphocyte transformation, as reflected in the response to phytohemagglutinin, accompanied by a specific defect in cellular immunity, as indicated by lymphocyte transformation to cytomegalovirus antigen. Eleven patients had cellular immunity to cytomegalovirus before transplantation, and all of these became negative in the first month after transplantation. In subsequent months, only 6 of the 14 study patients with cytomegalovirus infection developed specific cellular immune responses to cytomegalovirus. This occurred most often in patients who had severe febrile illnesses in association with infection. The specific cellular immune response which developed in the posttransplant period did not persist in three of the patients. This study demonstrates the dissociation of the humoral and cellular immune response to cytomegalovirus infection in renal transplant patients and indicates the importance of the loss of cellular immunity in the appearance of infection. Previously infected patients lost their cell-mediated immunity and had reactivation infections despite the presence of serum antibody.", "contents": "Cellular immune response to cytomegalovirus infection after renal transplantation. A prospective study of 15 patients who received renal transplants defined the effect of renal transplantation on the cellular immune response to cytomegalovirus infection. Of 15 patients, 14 developed cytomegalovirus infection, usually in the first 2 months after transplantation, and all infections were accompanied by a normal humoral immune response. After the initiation of immunosuppressive therapy and transplantation, there was a general depression of lymphocyte transformation, as reflected in the response to phytohemagglutinin, accompanied by a specific defect in cellular immunity, as indicated by lymphocyte transformation to cytomegalovirus antigen. Eleven patients had cellular immunity to cytomegalovirus before transplantation, and all of these became negative in the first month after transplantation. In subsequent months, only 6 of the 14 study patients with cytomegalovirus infection developed specific cellular immune responses to cytomegalovirus. This occurred most often in patients who had severe febrile illnesses in association with infection. The specific cellular immune response which developed in the posttransplant period did not persist in three of the patients. This study demonstrates the dissociation of the humoral and cellular immune response to cytomegalovirus infection in renal transplant patients and indicates the importance of the loss of cellular immunity in the appearance of infection. Previously infected patients lost their cell-mediated immunity and had reactivation infections despite the presence of serum antibody."}
{"id": "PMID:215542", "title": "Penetration of cultured mouse fibroblasts (L cells) by Rickettsia prowazeki.", "content": "The association of Rickettsia prowazeki with L cells was examined by using a novel radioactive assay in which [alpha-(32)P]ATP-labeled rickettsiae were incubated with L-cell monolayers. Rickettsial association with the monolayer involved adherence and internalization steps that could be experimentally distinguished. Since R. prowazeki but not L cells possess an ATP-ADP obligate exchange transport system, addition of excess unlabeled ATP resulted in exchange of the labeled ATP from external, adherent rickettsiae but not from internalized rickettsiae. Rickettsial association was temperature dependent and was a linear function of both time and concentration. More than 90% of the biologically active rickettsiae associated with L cells was internalized. Rickettsial internalization required active participation of both rickettsiae and L cells; inactivation of either greatly reduced internalization. Rickettsial adherence to poisoned L cells was a saturable function of time and concentration. Adherence showed less temperature dependence than did internalization, but like rickettsial internalization, the extent of adherence was extremely low at 0 degrees C. The rate and extent of adherence by inactivated and native rickettsiae to inactivated L cells were similar. Although inactive rickettsiae adhered to active and inactive L cells to a similar extent, inactive rickettsiae were internalized poorly by active L cells. These data form the basis for the hypothesis that R. prowazeki are internalized by the host cell through a process of \"induced phagocytosis\" and that inactivated rickettsiae adhere to the host cell differently from native rickettsiae, failing to trigger the endocytosis mechanism.", "contents": "Penetration of cultured mouse fibroblasts (L cells) by Rickettsia prowazeki. The association of Rickettsia prowazeki with L cells was examined by using a novel radioactive assay in which [alpha-(32)P]ATP-labeled rickettsiae were incubated with L-cell monolayers. Rickettsial association with the monolayer involved adherence and internalization steps that could be experimentally distinguished. Since R. prowazeki but not L cells possess an ATP-ADP obligate exchange transport system, addition of excess unlabeled ATP resulted in exchange of the labeled ATP from external, adherent rickettsiae but not from internalized rickettsiae. Rickettsial association was temperature dependent and was a linear function of both time and concentration. More than 90% of the biologically active rickettsiae associated with L cells was internalized. Rickettsial internalization required active participation of both rickettsiae and L cells; inactivation of either greatly reduced internalization. Rickettsial adherence to poisoned L cells was a saturable function of time and concentration. Adherence showed less temperature dependence than did internalization, but like rickettsial internalization, the extent of adherence was extremely low at 0 degrees C. The rate and extent of adherence by inactivated and native rickettsiae to inactivated L cells were similar. Although inactive rickettsiae adhered to active and inactive L cells to a similar extent, inactive rickettsiae were internalized poorly by active L cells. These data form the basis for the hypothesis that R. prowazeki are internalized by the host cell through a process of \"induced phagocytosis\" and that inactivated rickettsiae adhere to the host cell differently from native rickettsiae, failing to trigger the endocytosis mechanism."}
{"id": "PMID:215543", "title": "Protection against Marek's disease-derived tumor transplants by the nononcogenic SB-1 strain of Marek's disease virus.", "content": "A series of experiments was conducted to study the in vivo protection against Marek's disease-derived tumor transplants by the nononcogenic SB-1 strain of Marek's disease virus. Intact, embryonally bursectomized (Bx), thymectomized (Tx), or cyclophosphamide (Cy)-treated chickens of four genetic lines were vaccinated with live or inactivated SB-1. JMV, a non-virus-producing transplant, and GA/Tr-1 and MDT-198, two virus-producing transplants were used for challenge. Optimal protection against JMV was present 7 days postvaccination, but there was significant protection even when SB-1 and JMV were administered together. Protection was abolished by an increase in the number of tumor cells used for challenge or by combined Tx and Cy treatment. Inactivated SB-1-infected cells were unable to induce protection against JMV challenge. Protection was also present against challenge with GA/Tr-1, but not against MDT-198, except in vaccinated, Bx chickens. It was concluded that protection against JMV was T-cell dependent and required the induction of neo-antigens not present in an inactivated SB-1 cellular preparation. The absence of protection in intact chickens against MDT-198 could not be explained.", "contents": "Protection against Marek's disease-derived tumor transplants by the nononcogenic SB-1 strain of Marek's disease virus. A series of experiments was conducted to study the in vivo protection against Marek's disease-derived tumor transplants by the nononcogenic SB-1 strain of Marek's disease virus. Intact, embryonally bursectomized (Bx), thymectomized (Tx), or cyclophosphamide (Cy)-treated chickens of four genetic lines were vaccinated with live or inactivated SB-1. JMV, a non-virus-producing transplant, and GA/Tr-1 and MDT-198, two virus-producing transplants were used for challenge. Optimal protection against JMV was present 7 days postvaccination, but there was significant protection even when SB-1 and JMV were administered together. Protection was abolished by an increase in the number of tumor cells used for challenge or by combined Tx and Cy treatment. Inactivated SB-1-infected cells were unable to induce protection against JMV challenge. Protection was also present against challenge with GA/Tr-1, but not against MDT-198, except in vaccinated, Bx chickens. It was concluded that protection against JMV was T-cell dependent and required the induction of neo-antigens not present in an inactivated SB-1 cellular preparation. The absence of protection in intact chickens against MDT-198 could not be explained."}
{"id": "PMID:215544", "title": "Effect of Escherichia coli heat-stable enterotoxin on cyclic GMP levels in mouse intestine.", "content": "Partially purified heat-stable enterotoxin obtained from Escherichia coli strain F11/P155 caused an accumulation of cyclic GMP in the intestines of 8-day-old mice.", "contents": "Effect of Escherichia coli heat-stable enterotoxin on cyclic GMP levels in mouse intestine. Partially purified heat-stable enterotoxin obtained from Escherichia coli strain F11/P155 caused an accumulation of cyclic GMP in the intestines of 8-day-old mice."}
{"id": "PMID:215545", "title": "Biological properties of equine herpesvirus type 1 DNA: transfectivity and transforming capacity.", "content": "DNA extracted from purified virions of equine herpesvirus type 1 (EHV-1) was examined for its transfectivity and transforming ability. The infectivity of the herpesvirus DNA was demonstrated by addition of calcium phosphate-DNA  coprecipitates to monolayers of permissive horse cells, with resultant plaque formation. The efficiency of transfection (50 to 100 plaque-forming units/microgram of DNA) was reduced by treatment of the viral DNA with deoxyribonuclease or sonication but not with Pronase or antivirus neutralizing serum. When nonpermissive mouse 3T3 Cells lacking the enzyme thymidine kinase (TK-) were transfected with intact EHV-1 DNA, clones of cells transformed to the TK+ phenotype were isolated in selective HAT medium (hypoxanthine, aminopterin, thymidine), which prevents growth of the TK- parental phenotype. The efficiency of transformation ranged from one to five transformants per microgram of EHV-1 DNA. The TK activity of the biochemically transformed cells was characterized by biochemical, electrophoretic, and immunological techniques. By these criteria, the TK activity was identical to the EHV-1 TK and different from the host wild-type enzyme. In contrast to the parental TK+ 3T3 cells, the EHV-1-transformed TK+ cells were unable to grow in the presence of arabinosylthymine, a drug selectively phosphorylated by herpesvirus TKs. These results indicate that stable transfer of EHV-1 genes into nonpermissive cells can be achieved with purified viral DNA.", "contents": "Biological properties of equine herpesvirus type 1 DNA: transfectivity and transforming capacity. DNA extracted from purified virions of equine herpesvirus type 1 (EHV-1) was examined for its transfectivity and transforming ability. The infectivity of the herpesvirus DNA was demonstrated by addition of calcium phosphate-DNA  coprecipitates to monolayers of permissive horse cells, with resultant plaque formation. The efficiency of transfection (50 to 100 plaque-forming units/microgram of DNA) was reduced by treatment of the viral DNA with deoxyribonuclease or sonication but not with Pronase or antivirus neutralizing serum. When nonpermissive mouse 3T3 Cells lacking the enzyme thymidine kinase (TK-) were transfected with intact EHV-1 DNA, clones of cells transformed to the TK+ phenotype were isolated in selective HAT medium (hypoxanthine, aminopterin, thymidine), which prevents growth of the TK- parental phenotype. The efficiency of transformation ranged from one to five transformants per microgram of EHV-1 DNA. The TK activity of the biochemically transformed cells was characterized by biochemical, electrophoretic, and immunological techniques. By these criteria, the TK activity was identical to the EHV-1 TK and different from the host wild-type enzyme. In contrast to the parental TK+ 3T3 cells, the EHV-1-transformed TK+ cells were unable to grow in the presence of arabinosylthymine, a drug selectively phosphorylated by herpesvirus TKs. These results indicate that stable transfer of EHV-1 genes into nonpermissive cells can be achieved with purified viral DNA."}
{"id": "PMID:215546", "title": "In vitro evaluation of opsonic and cellular granulocyte function by luminol-dependent chemiluminescence: utility in patients with severe neutropenia and cellular deficiency states.", "content": "Actively phagocytizing polymorphonuclear leukocytes (PMN) emit light or chemiluminescence (CL) which has been shown to be linked to the oxidative activity of the PMN. The measurement of CL has been demonstrated to be a useful tool for the in vitro assessment of intracellular and opsonophagocytic function of PMN. We have increased the sensitivity of the CL measurement by the addition of luminol to the in vitro reaction of PMN, bacteria, and serum. The presence of luminol, which can be oxidized to emit light, amplifies the detection of CL and PMN cellular activity. This amplification effectively reduces the number of PMN that are necessary for assessment of PMN function from 1 x 10(7) to as low as 2 x 10(4) PMN/assay and permits the evaluation of PMN function in severely neutropenic patients (100 PMN/mm3) in whom cellular PMN function has been heretofore extremely difficult to assess by other methodology. When this luminol-dependent CL method was used, three of eight neutropenic leukemic patients with gram-negative septicemia were found to have deficient opsonic activity and/or increased or depressed cellular oxidative activity. Because the initial slope of CL is dependent on the amount of serum and heat-labile factors, this method can also be used effectively as a simple technique for the analysis of specific rates of opsonophagocytosis of various microorganisms. Additionally, this method can detect the cellular PMN abnormalities of chronic granulomatous disease and myeloperoxidase deficiency. The luminol-dependent CL method is a simple, sensitive, reproducible technique that provides useful information about PMN metabolic activity, particularly in studies in which the number of PMN is limited.", "contents": "In vitro evaluation of opsonic and cellular granulocyte function by luminol-dependent chemiluminescence: utility in patients with severe neutropenia and cellular deficiency states. Actively phagocytizing polymorphonuclear leukocytes (PMN) emit light or chemiluminescence (CL) which has been shown to be linked to the oxidative activity of the PMN. The measurement of CL has been demonstrated to be a useful tool for the in vitro assessment of intracellular and opsonophagocytic function of PMN. We have increased the sensitivity of the CL measurement by the addition of luminol to the in vitro reaction of PMN, bacteria, and serum. The presence of luminol, which can be oxidized to emit light, amplifies the detection of CL and PMN cellular activity. This amplification effectively reduces the number of PMN that are necessary for assessment of PMN function from 1 x 10(7) to as low as 2 x 10(4) PMN/assay and permits the evaluation of PMN function in severely neutropenic patients (100 PMN/mm3) in whom cellular PMN function has been heretofore extremely difficult to assess by other methodology. When this luminol-dependent CL method was used, three of eight neutropenic leukemic patients with gram-negative septicemia were found to have deficient opsonic activity and/or increased or depressed cellular oxidative activity. Because the initial slope of CL is dependent on the amount of serum and heat-labile factors, this method can also be used effectively as a simple technique for the analysis of specific rates of opsonophagocytosis of various microorganisms. Additionally, this method can detect the cellular PMN abnormalities of chronic granulomatous disease and myeloperoxidase deficiency. The luminol-dependent CL method is a simple, sensitive, reproducible technique that provides useful information about PMN metabolic activity, particularly in studies in which the number of PMN is limited."}
{"id": "PMID:215547", "title": "Enhancement of avian sarcoma virus-induced tumor growth after pretreatment with BCG.", "content": "Pretreatment of chickens with BCG 1 week before inoculation with avian sarcoma virus had a stimulatory effect on virus-induced tumor growth in 15 of 17 cases tested. This outcome was dependent upon the injection of both BCG and the oncogenic agent into the same wing web. Injection of BCG into the wing web contralateral to that used for virus inoculation or injection of a subcellular fraction of BCG into the same wing web did not affect tumor development. Administration of BCG also gave rise to heightened levels of tumor-associated, cell-mediated immunity, both on the part of chickens which received a subsequent injection of oncogenic virus as well as normal, BCG-inoculated controls.", "contents": "Enhancement of avian sarcoma virus-induced tumor growth after pretreatment with BCG. Pretreatment of chickens with BCG 1 week before inoculation with avian sarcoma virus had a stimulatory effect on virus-induced tumor growth in 15 of 17 cases tested. This outcome was dependent upon the injection of both BCG and the oncogenic agent into the same wing web. Injection of BCG into the wing web contralateral to that used for virus inoculation or injection of a subcellular fraction of BCG into the same wing web did not affect tumor development. Administration of BCG also gave rise to heightened levels of tumor-associated, cell-mediated immunity, both on the part of chickens which received a subsequent injection of oncogenic virus as well as normal, BCG-inoculated controls."}
{"id": "PMID:215548", "title": "Comparison of various macrophage-inhibitory agents on vaginal and systemic herpes simplex virus type 2 infections.", "content": "Pretreatment of mice intraperitoneally with silica, trypan blue, or dextran sulfate to inhibit macrophage function markedly increased the lethality of a systemic intravenous infection with herpes simplex virus type 2, but did not affect the lethality or local virus growth after vaginal infection of mice with herpes simplex virus type 2. Agents which inhibit macrophage function by different mechanisms decreased host resistance to herpes simplex virus type 2, but the effects of macrophage-inhibitory agents may vary according to the route of virus infection.", "contents": "Comparison of various macrophage-inhibitory agents on vaginal and systemic herpes simplex virus type 2 infections. Pretreatment of mice intraperitoneally with silica, trypan blue, or dextran sulfate to inhibit macrophage function markedly increased the lethality of a systemic intravenous infection with herpes simplex virus type 2, but did not affect the lethality or local virus growth after vaginal infection of mice with herpes simplex virus type 2. Agents which inhibit macrophage function by different mechanisms decreased host resistance to herpes simplex virus type 2, but the effects of macrophage-inhibitory agents may vary according to the route of virus infection."}
{"id": "PMID:215549", "title": "Comparative studies of five heat-labile toxic products of Escherichia coli.", "content": "Five heat-labile, partially purified toxic products of Escherichia coli were distinguished by isoelectric focusing, molecular weight, and neutralization with homologous and heterologous antisera. Only two affected the morphology of Y-1 cells, induced fluid accumulation in rabbit ileal loops, and stimulated production of cyclic AMP in Vero cells; these two did not cross-neutralize and only one showed cross-neutralization with cholera antitoxin. The remaining three products were cytotoxic for Vero cells.", "contents": "Comparative studies of five heat-labile toxic products of Escherichia coli. Five heat-labile, partially purified toxic products of Escherichia coli were distinguished by isoelectric focusing, molecular weight, and neutralization with homologous and heterologous antisera. Only two affected the morphology of Y-1 cells, induced fluid accumulation in rabbit ileal loops, and stimulated production of cyclic AMP in Vero cells; these two did not cross-neutralize and only one showed cross-neutralization with cholera antitoxin. The remaining three products were cytotoxic for Vero cells."}
{"id": "PMID:215550", "title": "Induction of enhanced resistance against encephalomyocarditis virus infection of mice by nonviable Mycobacterium tuberculosis: mechanisms of protection.", "content": "Nonviable Mycobacterium tuberculosis strain Jamaica suspended in oil-droplet emulsions was used to enhance resistance of mice against encephalomyocarditis virus (EMCV). The mycobacteria-injected mice were significantly resistant to 50,000 50% lethal doses of EMCV. Similar concentrations of virus in plasma of normal and mycobacteria-injected mice from 1 to 120 min after injection of EMCV showed that resistance was not a result of rapid elimination of virus from the circulation. Furthermore, survival of viremic mice indicated protective mechanisms were operative after EMCV had escaped primary surveillance. Resistance did not appear to be associated with the mouse major histocompatibility gene complex. The spleen was intimately associated with protection, and the thymus was nonessential for enhanced resistance to EMCV. Protection was significantly diminished by cyclophosphamide injected intraperitoneally from 3 days before to the day of virus challenge. Finally, silica given intraperitoneally 24 h before virus completely abrogated resistance of mycobacteria-injected mice to EMCV. These results suggest that macrophages functioning independently of T-lymphocytes are important effector cells in resistance to EMCV of mice injected with nonviable mycobacteria.", "contents": "Induction of enhanced resistance against encephalomyocarditis virus infection of mice by nonviable Mycobacterium tuberculosis: mechanisms of protection. Nonviable Mycobacterium tuberculosis strain Jamaica suspended in oil-droplet emulsions was used to enhance resistance of mice against encephalomyocarditis virus (EMCV). The mycobacteria-injected mice were significantly resistant to 50,000 50% lethal doses of EMCV. Similar concentrations of virus in plasma of normal and mycobacteria-injected mice from 1 to 120 min after injection of EMCV showed that resistance was not a result of rapid elimination of virus from the circulation. Furthermore, survival of viremic mice indicated protective mechanisms were operative after EMCV had escaped primary surveillance. Resistance did not appear to be associated with the mouse major histocompatibility gene complex. The spleen was intimately associated with protection, and the thymus was nonessential for enhanced resistance to EMCV. Protection was significantly diminished by cyclophosphamide injected intraperitoneally from 3 days before to the day of virus challenge. Finally, silica given intraperitoneally 24 h before virus completely abrogated resistance of mycobacteria-injected mice to EMCV. These results suggest that macrophages functioning independently of T-lymphocytes are important effector cells in resistance to EMCV of mice injected with nonviable mycobacteria."}
{"id": "PMID:215551", "title": "Suppression of in vitro growth of virulent and avirulent herpes simplex viruses by cell-mediated immune mechanisms, antibody, and interferon.", "content": "A rounding cell-forming--GC strain, which is a variant of a syncytial giant cell-forming herpes simplex virus (+GC Miyama strain), was highly attenuated for Swiss, BALB/c nu/nu, and nu/+ mice, whereas +GC was highly virulent to all the mice tested. +GC and -GC were antigenically indistinguishable from each other by cross-neutralization and cross-immunization. Immunosuppression induced by cyclophosphamide converted the nonlethal -GC infection of mice into a fatal infection. -GC replication in tissue culture was more effectively suppressed by spleen cells immunized with either +GC or -GC than was the +GC replication. -GC replication was also inhibited more effectively by antibody or the antibody-dependent cell-mediated system than was the +GC replication. -GC is highly sensitive to mouse interferon, but +GC was relatively resistant. These findings indicate that attenuation of this avirulent -GC strain may be due to a high susceptibility of its replication to humoral and cell-mediated defense factors. The probable roles of each defense factor in recovery from the infection with virulent and attenuated herpes simplex virus are also discussed.", "contents": "Suppression of in vitro growth of virulent and avirulent herpes simplex viruses by cell-mediated immune mechanisms, antibody, and interferon. A rounding cell-forming--GC strain, which is a variant of a syncytial giant cell-forming herpes simplex virus (+GC Miyama strain), was highly attenuated for Swiss, BALB/c nu/nu, and nu/+ mice, whereas +GC was highly virulent to all the mice tested. +GC and -GC were antigenically indistinguishable from each other by cross-neutralization and cross-immunization. Immunosuppression induced by cyclophosphamide converted the nonlethal -GC infection of mice into a fatal infection. -GC replication in tissue culture was more effectively suppressed by spleen cells immunized with either +GC or -GC than was the +GC replication. -GC replication was also inhibited more effectively by antibody or the antibody-dependent cell-mediated system than was the +GC replication. -GC is highly sensitive to mouse interferon, but +GC was relatively resistant. These findings indicate that attenuation of this avirulent -GC strain may be due to a high susceptibility of its replication to humoral and cell-mediated defense factors. The probable roles of each defense factor in recovery from the infection with virulent and attenuated herpes simplex virus are also discussed."}
{"id": "PMID:215552", "title": "Characterization of mouse peritoneal exudate and associated leukocyte adherence inhibitory activity after intraperitoneal injection of either Bordetella pertussis or Corynebacterium parvum vaccines.", "content": "Bordetella pertussis and Corynebacterium parvum are commonly used immunopotentiating agents. To explore the inflammatory environment induced by these agents, the peritoneal exudate response in mice following intraperitoneal injection of B. pertussis (PV) and C. parvum (CV) vaccines was investigated. The PV-induced exudate isolated by lavage was characterized by an early neutrophil influx followed by enhanced accumulation of mononuclear cells and fluid protein. The CV exudate was principally mononuclear in nature and displayed fewer numbers of cells and less fluid protein. Both vaccines also enhanced the leukocyte adherence inhibitory activity (LAIA) of peritoneal fluid as measured in vitro. The development of exudate LAIA was T lymphocyte independent. A similar LAIA was demonstrated in nonimmune mouse plasma and serum. Exudate fluid and serum LAIA were heat stable and trypsin sensitive. These studies suggest that significant differences exist in the composition of the local tissue environment following PV and CV injection and that exudate LAIA is serum derived. Further studies in this direction should result in a better understanding of the ways in which inflammatory cells and fluid substances affect lymphocyte-macrophage interaction subsequent to adjuvant administration.", "contents": "Characterization of mouse peritoneal exudate and associated leukocyte adherence inhibitory activity after intraperitoneal injection of either Bordetella pertussis or Corynebacterium parvum vaccines. Bordetella pertussis and Corynebacterium parvum are commonly used immunopotentiating agents. To explore the inflammatory environment induced by these agents, the peritoneal exudate response in mice following intraperitoneal injection of B. pertussis (PV) and C. parvum (CV) vaccines was investigated. The PV-induced exudate isolated by lavage was characterized by an early neutrophil influx followed by enhanced accumulation of mononuclear cells and fluid protein. The CV exudate was principally mononuclear in nature and displayed fewer numbers of cells and less fluid protein. Both vaccines also enhanced the leukocyte adherence inhibitory activity (LAIA) of peritoneal fluid as measured in vitro. The development of exudate LAIA was T lymphocyte independent. A similar LAIA was demonstrated in nonimmune mouse plasma and serum. Exudate fluid and serum LAIA were heat stable and trypsin sensitive. These studies suggest that significant differences exist in the composition of the local tissue environment following PV and CV injection and that exudate LAIA is serum derived. Further studies in this direction should result in a better understanding of the ways in which inflammatory cells and fluid substances affect lymphocyte-macrophage interaction subsequent to adjuvant administration."}
{"id": "PMID:215553", "title": "Immunoglobulin G to virus-specific early antigens in congenital, primary, and reactivated human cytomegalovirus infections.", "content": "Immunoglobulin G antibody to human cytomegalovirus (CMV)-specific early antigens (EA-Ab) was determined by the immunoperoxidase antibody technique in several cases of congenital, primary, and reactivated CMV infections. Mothers of congenitally infected infants and a group of leukemic children and pregnant women were also studied. In 11 cases of congenital infection, CMV EA-Ab was always associated with CMV excretion whether immunoglobulin M antibody was present or not. Nine mothers of congenitally infected infants had CMV EA-Ab for several months after delivery, but association with CMV elimination was not established when urine and/or saliva were tested for virus isolation. In all nine cases of primary CMV infection, CMV EA-Ab was present, and in five its detection was associated with CMV isolation. In one case, disappearance of EA-Ab occurred when virus excretion ceased. In five cases of reactivated CMV infections, a consistent association between CMV EA-Ab and virus isolation was found. Six of 31 leukemia children had CMV EA-Ab, and virus was isolated from 3 of these. Four of 28 pregnant women showed EA-Ab in their serum, but tests for isolation were not done. These data suggest that CMV EA-Ab is not a marker of a current primary CMV infection, as previously reported, but a marker of an active CMV replication which can take place in primary as well as in congenital and reactivated CMV infections.", "contents": "Immunoglobulin G to virus-specific early antigens in congenital, primary, and reactivated human cytomegalovirus infections. Immunoglobulin G antibody to human cytomegalovirus (CMV)-specific early antigens (EA-Ab) was determined by the immunoperoxidase antibody technique in several cases of congenital, primary, and reactivated CMV infections. Mothers of congenitally infected infants and a group of leukemic children and pregnant women were also studied. In 11 cases of congenital infection, CMV EA-Ab was always associated with CMV excretion whether immunoglobulin M antibody was present or not. Nine mothers of congenitally infected infants had CMV EA-Ab for several months after delivery, but association with CMV elimination was not established when urine and/or saliva were tested for virus isolation. In all nine cases of primary CMV infection, CMV EA-Ab was present, and in five its detection was associated with CMV isolation. In one case, disappearance of EA-Ab occurred when virus excretion ceased. In five cases of reactivated CMV infections, a consistent association between CMV EA-Ab and virus isolation was found. Six of 31 leukemia children had CMV EA-Ab, and virus was isolated from 3 of these. Four of 28 pregnant women showed EA-Ab in their serum, but tests for isolation were not done. These data suggest that CMV EA-Ab is not a marker of a current primary CMV infection, as previously reported, but a marker of an active CMV replication which can take place in primary as well as in congenital and reactivated CMV infections."}
{"id": "PMID:215554", "title": "Characterization of anemia induced by avian osteopetrosis virus.", "content": "Chickens infected intravenously at 8 days after hatching with an avian osteopetrosis virus developed a severe, progressive anemia in the absence of osteopetrosis. The anemia was characterized as a pancytopenia, in which erythrocytes, granulocytes, and thrombocytes decreased concomitantly. Serum bilirubin levels were normal, whereas erythrocytes from infected chickens demonstrated a slightly elevated osmotic fragility. A negative Coombs test indicated that there was no evidence for erythrocyte-bound antibody. Erythrocytes from infected animals had slightly decreased 51Cr-labeled erythrocyte survival time when compared with normal. Examination of marrow histological preparations, together with ferrokinetic studies with 59Fe, indicated that marrow failure occurred during the acute phase of the anemia. Circulating virus was present during the development and acute phases of the anemia, but disappeared during the recovery phase of the disease. Neutralizing antibody appeared after the disappearance of circulating virus. It is concluded that virus infection induced both marrow failure (aplastic crisis) and decreased erythrocyte survival.", "contents": "Characterization of anemia induced by avian osteopetrosis virus. Chickens infected intravenously at 8 days after hatching with an avian osteopetrosis virus developed a severe, progressive anemia in the absence of osteopetrosis. The anemia was characterized as a pancytopenia, in which erythrocytes, granulocytes, and thrombocytes decreased concomitantly. Serum bilirubin levels were normal, whereas erythrocytes from infected chickens demonstrated a slightly elevated osmotic fragility. A negative Coombs test indicated that there was no evidence for erythrocyte-bound antibody. Erythrocytes from infected animals had slightly decreased 51Cr-labeled erythrocyte survival time when compared with normal. Examination of marrow histological preparations, together with ferrokinetic studies with 59Fe, indicated that marrow failure occurred during the acute phase of the anemia. Circulating virus was present during the development and acute phases of the anemia, but disappeared during the recovery phase of the disease. Neutralizing antibody appeared after the disappearance of circulating virus. It is concluded that virus infection induced both marrow failure (aplastic crisis) and decreased erythrocyte survival."}
{"id": "PMID:215555", "title": "Effect of erythromycin and amoxycillin on Bordetella pertussis in the nasopharynx.", "content": "The effectiveness of oral erythromycin and amoxycillin in eradicating Bordetella pertussis from the nasopharynx was compared. Erythromycin in a dosage of 40--50 mg/kg/day was significantly more effective than amoxycillin in a dosage of 25--30 mg/kg/day. The organism did not disappear in three cases receiving a lower dosage of erythromycin. As antibiotic treatment does not affect the clinical course of fully-developed whooping cough, erythromycin is indicated primarily when particularly susceptible individuals are threatened by exposure. In such cases erythromycin should be given as soon as whooping cough is suspected.", "contents": "Effect of erythromycin and amoxycillin on Bordetella pertussis in the nasopharynx. The effectiveness of oral erythromycin and amoxycillin in eradicating Bordetella pertussis from the nasopharynx was compared. Erythromycin in a dosage of 40--50 mg/kg/day was significantly more effective than amoxycillin in a dosage of 25--30 mg/kg/day. The organism did not disappear in three cases receiving a lower dosage of erythromycin. As antibiotic treatment does not affect the clinical course of fully-developed whooping cough, erythromycin is indicated primarily when particularly susceptible individuals are threatened by exposure. In such cases erythromycin should be given as soon as whooping cough is suspected."}
{"id": "PMID:215556", "title": "Tourist hepatitis, antibodies to hepatitis A virus and immune serum globulin prophylaxis.", "content": "Immune serum globulin prophylaxis for foreign travellers should be reserved for those at high risk having no immunity against hepatitis A. In this study from Sweden the incidence of tourist hepatitis in different age groups was correlated to the prevalence of antibodies to hepatitis A virus (anti-HAV) in the population. 58% of individuals over 50 years had anti-HAV and travellers in these ages seldom experienced \"tourist hepatitis\". In younger age groups a low prevalence of anti-HAV (11%) was combined with a higher incidence of tourist hepatitis.", "contents": "Tourist hepatitis, antibodies to hepatitis A virus and immune serum globulin prophylaxis. Immune serum globulin prophylaxis for foreign travellers should be reserved for those at high risk having no immunity against hepatitis A. In this study from Sweden the incidence of tourist hepatitis in different age groups was correlated to the prevalence of antibodies to hepatitis A virus (anti-HAV) in the population. 58% of individuals over 50 years had anti-HAV and travellers in these ages seldom experienced \"tourist hepatitis\". In younger age groups a low prevalence of anti-HAV (11%) was combined with a higher incidence of tourist hepatitis."}
{"id": "PMID:215557", "title": "Decrease in incidence of hepatitis A infections in Germany.", "content": "The hypothesis of a decline in the incidence of hepatitis A infections in Germany in recent decades was confirmed by determining the prevalence of hepatitis A antibody (anti-HAV) in sera collected in 1965 and in 1975 under the same conditions in North Germany. The prevalence of anti-HAV correlated with the year of birth and was independent of the time of serum sampling. The force of infection fell from 0.04 in 1945 to 0.005 in 1965 as judged from a catalytic epidemic model with a sigmoidal decrease.", "contents": "Decrease in incidence of hepatitis A infections in Germany. The hypothesis of a decline in the incidence of hepatitis A infections in Germany in recent decades was confirmed by determining the prevalence of hepatitis A antibody (anti-HAV) in sera collected in 1965 and in 1975 under the same conditions in North Germany. The prevalence of anti-HAV correlated with the year of birth and was independent of the time of serum sampling. The force of infection fell from 0.04 in 1945 to 0.005 in 1965 as judged from a catalytic epidemic model with a sigmoidal decrease."}
{"id": "PMID:215558", "title": "Identification of murine endogenous xenotropic retrovirus in cultured multicellular tumour spheroids from nude-mouse-passaged nasopharyngeal carcinoma.", "content": "After nude-mouse-passage, a carcinoma of the nasopharynx was found to contain a few scattered C-type retrovirus particles. Culture of this nude-mouse-grown material over solid agar allowed the human tumour cells to grow as multicellular spheroids which increased in number by budding and could be subcultured for up to 6 months. Within the spheroids the human tumour cells expressed increased retrovirus replication and large numbers of C-type particles were observed. Treatment with a halogenated pyrimidine further enhanced the virus production. This tissue culture system provided sufficient virus production for the identification of the retrovirus as an endogenous xenotropic murine leukaemia virus and not a human agent.", "contents": "Identification of murine endogenous xenotropic retrovirus in cultured multicellular tumour spheroids from nude-mouse-passaged nasopharyngeal carcinoma. After nude-mouse-passage, a carcinoma of the nasopharynx was found to contain a few scattered C-type retrovirus particles. Culture of this nude-mouse-grown material over solid agar allowed the human tumour cells to grow as multicellular spheroids which increased in number by budding and could be subcultured for up to 6 months. Within the spheroids the human tumour cells expressed increased retrovirus replication and large numbers of C-type particles were observed. Treatment with a halogenated pyrimidine further enhanced the virus production. This tissue culture system provided sufficient virus production for the identification of the retrovirus as an endogenous xenotropic murine leukaemia virus and not a human agent."}
{"id": "PMID:215559", "title": "Burkitt's lymphoma in Iraq. Clinical and pathological study of forty-seven patients.", "content": "The clinical and pathological features of 47 patients with Burkitt's lymphoma seen at the University of Baghdad Teaching Hospital over the years 1969-1977 are described. There were 30 males and 17 females with a mean age of 7.5 years. All patients presented with advanced disease; 44 were in Stage III and 3 in Stage IV, (1 with central nervous system involvement; 1 with bone-marrow involvement; 1 presented as acute leukaemia). The abdomen, with or without other sites, was involved in 42 patients. Thirty-four patients died within 18 months, 11 in the immediate post-operative period. Cyclophosphamide in variable dosages was administered to 29 patients with a good response in 15. The 3 patients with Stage IV disease died with poor response to therapy. Thus, in Iraq, a non-endemic area for the disease, Burkitt's lymphoma seems to have somewhat different clinical and pathological features from the endemic (African), or the rare, sporadic disease reported elsewhere.", "contents": "Burkitt's lymphoma in Iraq. Clinical and pathological study of forty-seven patients. The clinical and pathological features of 47 patients with Burkitt's lymphoma seen at the University of Baghdad Teaching Hospital over the years 1969-1977 are described. There were 30 males and 17 females with a mean age of 7.5 years. All patients presented with advanced disease; 44 were in Stage III and 3 in Stage IV, (1 with central nervous system involvement; 1 with bone-marrow involvement; 1 presented as acute leukaemia). The abdomen, with or without other sites, was involved in 42 patients. Thirty-four patients died within 18 months, 11 in the immediate post-operative period. Cyclophosphamide in variable dosages was administered to 29 patients with a good response in 15. The 3 patients with Stage IV disease died with poor response to therapy. Thus, in Iraq, a non-endemic area for the disease, Burkitt's lymphoma seems to have somewhat different clinical and pathological features from the endemic (African), or the rare, sporadic disease reported elsewhere."}
{"id": "PMID:215561", "title": "14q+ marker chromosome in an EBV-genome-negative lymph node without signs of malignancy in a patient with EBV-genome-positive nasopharyngeal carcinoma.", "content": "In a patient with an EBV-genome-positive nasopharyngeal carcinoma, an EBV-genome-negative inguinal lymph node without histological evidence of malignant lymphoma or metastatic carcinoma growth was found to contain a 14q+ marker chromosome, identified as an 8;14 translocation, in all cells analyzed. This observation indicates that chromosome aberrations may precede histological signs of malignancy. The possible implication of this finding in relation to the postulated role of the 14q+ marker and lymphoma development is discussed.", "contents": "14q+ marker chromosome in an EBV-genome-negative lymph node without signs of malignancy in a patient with EBV-genome-positive nasopharyngeal carcinoma. In a patient with an EBV-genome-positive nasopharyngeal carcinoma, an EBV-genome-negative inguinal lymph node without histological evidence of malignant lymphoma or metastatic carcinoma growth was found to contain a 14q+ marker chromosome, identified as an 8;14 translocation, in all cells analyzed. This observation indicates that chromosome aberrations may precede histological signs of malignancy. The possible implication of this finding in relation to the postulated role of the 14q+ marker and lymphoma development is discussed."}
{"id": "PMID:215562", "title": "Correlated expression of a B-lymphocyte-specific glycoprotein (gp27/35) and the EBV receptor/C3 receptor complex in sublines from the same Burkitt lymphoma.", "content": "A series of virus-producer and non-producer sublines, derived from the Burkitt lymphoma line Jijoye and its P3HR-1 clone, were previously found to differ in the expression of EBV receptors and, in parallel, C3 receptors. The differences could be related to an \"internal selection\" caused by the cytopathic P3HR-1 virus variant, favouring the growth of receptor-negative cells. We have now analyzed the same lines for the expression of a B-lymphocyte-specific glycoprotein (gp27/35). A close parallellism was found between the expression of the EBV receptor-complement receptor complex and the glycoprotein, measured by quantitative absorption. The results favour a relationship between gp27/35 and EBV/C3 receptor expression.", "contents": "Correlated expression of a B-lymphocyte-specific glycoprotein (gp27/35) and the EBV receptor/C3 receptor complex in sublines from the same Burkitt lymphoma. A series of virus-producer and non-producer sublines, derived from the Burkitt lymphoma line Jijoye and its P3HR-1 clone, were previously found to differ in the expression of EBV receptors and, in parallel, C3 receptors. The differences could be related to an \"internal selection\" caused by the cytopathic P3HR-1 virus variant, favouring the growth of receptor-negative cells. We have now analyzed the same lines for the expression of a B-lymphocyte-specific glycoprotein (gp27/35). A close parallellism was found between the expression of the EBV receptor-complement receptor complex and the glycoprotein, measured by quantitative absorption. The results favour a relationship between gp27/35 and EBV/C3 receptor expression."}
{"id": "PMID:215564", "title": "Cell-density-dependence for growth in agarose of two human lymphoma lines and its decrease after Epstein-Barr virus conversion.", "content": "We have compared the growth in agarose medium of two EBV-negative Burkitt lymphoma lines, BJAB and Ramos, and that of their EBV-converted derivatives. Optimal conditions for growth in agarose medium are described. The original EBV-negative lines can grow in agarose to a high efficiency, provided a critical level of cell concentration is attained. Below this level, there is no growth at all. EBV-converted sublines form colonies at a much lower cell concentration, and their maximal plating efficiency is higher. These differences may be related to a super-transformation state induced in these cells by EBV.", "contents": "Cell-density-dependence for growth in agarose of two human lymphoma lines and its decrease after Epstein-Barr virus conversion. We have compared the growth in agarose medium of two EBV-negative Burkitt lymphoma lines, BJAB and Ramos, and that of their EBV-converted derivatives. Optimal conditions for growth in agarose medium are described. The original EBV-negative lines can grow in agarose to a high efficiency, provided a critical level of cell concentration is attained. Below this level, there is no growth at all. EBV-converted sublines form colonies at a much lower cell concentration, and their maximal plating efficiency is higher. These differences may be related to a super-transformation state induced in these cells by EBV."}
{"id": "PMID:215565", "title": "Biochemical identification of primate lymphoid cell-surface glycoproteins.", "content": "We have employed the galactose oxidase-tritiated sodium borohydride labelling method to examine the surface glycoproteins of cotton-topped marmoset and other primate cell lines either established from tumors or transformed in vitro by different lymphotropic herpesviruses. The labelled surface glycoproteins were separated on acrylamide gels in the presence of sodium dodecyl sulfate (SDS) and analyzed by fluorography. Our results indicate that (1) lymphocytes of the same class from different primate species are similar but can be distinguished; (2) T and B lymphocytes of the same species can be differentiated; (3) cotton-topped marmoset lymphocytes of the same class show marked similarities regardless of tumor or in vitro origin or virus used for transformation; (4) three cell lines established from different EBV-induced tumors of the same marmoset show essentially the same labelling pattern, supporting the hypothesis that they originated from a single clone.", "contents": "Biochemical identification of primate lymphoid cell-surface glycoproteins. We have employed the galactose oxidase-tritiated sodium borohydride labelling method to examine the surface glycoproteins of cotton-topped marmoset and other primate cell lines either established from tumors or transformed in vitro by different lymphotropic herpesviruses. The labelled surface glycoproteins were separated on acrylamide gels in the presence of sodium dodecyl sulfate (SDS) and analyzed by fluorography. Our results indicate that (1) lymphocytes of the same class from different primate species are similar but can be distinguished; (2) T and B lymphocytes of the same species can be differentiated; (3) cotton-topped marmoset lymphocytes of the same class show marked similarities regardless of tumor or in vitro origin or virus used for transformation; (4) three cell lines established from different EBV-induced tumors of the same marmoset show essentially the same labelling pattern, supporting the hypothesis that they originated from a single clone."}
{"id": "PMID:215568", "title": "Malignant fibrous histiocytoma of the temporomandiblar joint. Report of a case.", "content": "A case of malignant fibrous histiocytoma of the temporomandibular joint in a 21-year-old Japanese female was presented. The patient died of the tumor with local aggressive growth but without any organ metastasis, despite the intensive treatment including radical operation of the tumor, irradiation, and chemotherapy. This case suggested that radical curative operation was the only method of the treatment for this tumor. The clinicopathological features of the tumor are discussed, making reference to the malignant fibrous histiocytoma.", "contents": "Malignant fibrous histiocytoma of the temporomandiblar joint. Report of a case. A case of malignant fibrous histiocytoma of the temporomandibular joint in a 21-year-old Japanese female was presented. The patient died of the tumor with local aggressive growth but without any organ metastasis, despite the intensive treatment including radical operation of the tumor, irradiation, and chemotherapy. This case suggested that radical curative operation was the only method of the treatment for this tumor. The clinicopathological features of the tumor are discussed, making reference to the malignant fibrous histiocytoma."}
{"id": "PMID:215569", "title": "An amphetamine model of manic depressive illness.", "content": "Many features of manic-depressive illness can be mimicked in man by the use and withdrawal of amphetamines. In higher doses these drugs induce a syndrome virtually indistinguishable from paranoid schizophrenia. In this paper, some of the biochemical and physiological effects of the amphetamines are examined with the hope of clarifying the nature of the biological changes in these two major functional psychoses. The actions of the amphetamines are shown to reveal the operation of specific homeostatic or adaptive nervous mechanisms. These appear likely also to operate in adaptation to psychological stress. Evidence is presented that these mechanisms are malfunctioning in manic-depressive and acute schizophrenic states and that this accounts for many of the clinical features of these conditions.", "contents": "An amphetamine model of manic depressive illness. Many features of manic-depressive illness can be mimicked in man by the use and withdrawal of amphetamines. In higher doses these drugs induce a syndrome virtually indistinguishable from paranoid schizophrenia. In this paper, some of the biochemical and physiological effects of the amphetamines are examined with the hope of clarifying the nature of the biological changes in these two major functional psychoses. The actions of the amphetamines are shown to reveal the operation of specific homeostatic or adaptive nervous mechanisms. These appear likely also to operate in adaptation to psychological stress. Evidence is presented that these mechanisms are malfunctioning in manic-depressive and acute schizophrenic states and that this accounts for many of the clinical features of these conditions."}
{"id": "PMID:215566", "title": "Phagocytosis in leprosy. 2. Production of superoxide by circulating blood leukocytes from lepromatous patients.", "content": "The ability of polymorphonuclear leukocytes from lepromatous patients to produce superoxide (O-2) anion while phagocytizing latex particles was studied. The results were compared with those obtained in a group composed of normal individuals. No differences were found between lepromatous and normal groups. No differences were found either when the comparison was made between patients showing any form of leprosy reaction and patients without leprosy complications at the time of the study. Together with other results previously reported, our findings suggest that PMN from lepromatous patients are not different from PMN from healthy individuals with respect to their ability to generate and show the metabolic oxidative changes (as measured by the NBT- and the O-2-tests) induced by in vitro phagocytosis of latex particles. These metabolic activities remain normal even when PMN may show alterations at other levels of the phagocytic process.", "contents": "Phagocytosis in leprosy. 2. Production of superoxide by circulating blood leukocytes from lepromatous patients. The ability of polymorphonuclear leukocytes from lepromatous patients to produce superoxide (O-2) anion while phagocytizing latex particles was studied. The results were compared with those obtained in a group composed of normal individuals. No differences were found between lepromatous and normal groups. No differences were found either when the comparison was made between patients showing any form of leprosy reaction and patients without leprosy complications at the time of the study. Together with other results previously reported, our findings suggest that PMN from lepromatous patients are not different from PMN from healthy individuals with respect to their ability to generate and show the metabolic oxidative changes (as measured by the NBT- and the O-2-tests) induced by in vitro phagocytosis of latex particles. These metabolic activities remain normal even when PMN may show alterations at other levels of the phagocytic process."}
{"id": "PMID:215572", "title": "Circulating immune complexes in African mothers and their newborns.", "content": "Circulating immune complexes were measured using the Clq-binding test in 185 African mothers and their newborns at delivery. Results were compared to non-pregnant African women, healthy European blood donors and to a group of European mothers and their newborns. Clq-binding activity was increased in African mothers and in non-pregnant African women. Circulating immune complexes rarely occurred in cord blood even when mothers showed a high Clq-binding activity. The levels of immune complexes were unrelated to malaria. Complement components Clq and C3 were lower in the newborns than in the mothers.", "contents": "Circulating immune complexes in African mothers and their newborns. Circulating immune complexes were measured using the Clq-binding test in 185 African mothers and their newborns at delivery. Results were compared to non-pregnant African women, healthy European blood donors and to a group of European mothers and their newborns. Clq-binding activity was increased in African mothers and in non-pregnant African women. Circulating immune complexes rarely occurred in cord blood even when mothers showed a high Clq-binding activity. The levels of immune complexes were unrelated to malaria. Complement components Clq and C3 were lower in the newborns than in the mothers."}
{"id": "PMID:215574", "title": "A study of 204 consecutive deliveries in Abidjan--Anthropometric data of newborns, mothers and placentas.", "content": "Anthropometric measurements of newborns, mothers and placentas were taken in 204 consecutive deliveries at Adjam\u00e9 Maternity Hospital in Abidjan. Aclinical assessment of gestational age was made. Low mean birthweight can be attributed to a higher incidence of pre-term newborns in the present sample. Incidence of small for gestational age and large for gestational age babies is similar to that found in developed countries. Detailed analysis of correlations between maternal, placental and neonatal variables show that birthweight is dependent on nutritional status of the mothers and on size of the placenta. Young primiparae are shown to become pregnant before reaching full growth. Their weight and weight for height are significantly lower than for multiparae. The main group at risk for impaired foetal growth, prematurity and low birthweight are the children born to primiparous mothers.", "contents": "A study of 204 consecutive deliveries in Abidjan--Anthropometric data of newborns, mothers and placentas. Anthropometric measurements of newborns, mothers and placentas were taken in 204 consecutive deliveries at Adjam\u00e9 Maternity Hospital in Abidjan. Aclinical assessment of gestational age was made. Low mean birthweight can be attributed to a higher incidence of pre-term newborns in the present sample. Incidence of small for gestational age and large for gestational age babies is similar to that found in developed countries. Detailed analysis of correlations between maternal, placental and neonatal variables show that birthweight is dependent on nutritional status of the mothers and on size of the placenta. Young primiparae are shown to become pregnant before reaching full growth. Their weight and weight for height are significantly lower than for multiparae. The main group at risk for impaired foetal growth, prematurity and low birthweight are the children born to primiparous mothers."}
{"id": "PMID:215575", "title": "Maternal anaemia in Abidjan--Its influence on placenta and newborns.", "content": "In a random population of 198 pregnant women, detailed haematological determinations were performed at delivery. The prevalence of anaemia (haemoglobin less than 10 g/100 ml) is 20%. Iron deficiency is even more frequent. Malaria is shown to play an important role. Maternal anaemia is also correlated with nutritional status. Primiparae are shown to be at higher risk of anaemia. The effect of maternal anaemia on anthropometric and haematological variables of the newborn are discussed. Mothers with sickle-cell or HbC trait are not at special risk of anaemia.", "contents": "Maternal anaemia in Abidjan--Its influence on placenta and newborns. In a random population of 198 pregnant women, detailed haematological determinations were performed at delivery. The prevalence of anaemia (haemoglobin less than 10 g/100 ml) is 20%. Iron deficiency is even more frequent. Malaria is shown to play an important role. Maternal anaemia is also correlated with nutritional status. Primiparae are shown to be at higher risk of anaemia. The effect of maternal anaemia on anthropometric and haematological variables of the newborn are discussed. Mothers with sickle-cell or HbC trait are not at special risk of anaemia."}
{"id": "PMID:215576", "title": "Malaria at delivery in Abidjan.", "content": "In 198 consecutive deliveries in a region holoendemic for malaria, 39.4% of the mothers had malarial parasitaemia. Cord blood parasitaemia was found in 43 cases (55% of infected mothers). The incidence of malaria decreased with increasing parity possibly related to age. Malaria is partly responsible of the low birthweights and of the genesis of pre-term and small for date babies. A correlation between nutritional status and malarial infection was shown. According to IgM concentrations in cord blood, 2.5% of newborns had an intrauterine infection of unknown origin.", "contents": "Malaria at delivery in Abidjan. In 198 consecutive deliveries in a region holoendemic for malaria, 39.4% of the mothers had malarial parasitaemia. Cord blood parasitaemia was found in 43 cases (55% of infected mothers). The incidence of malaria decreased with increasing parity possibly related to age. Malaria is partly responsible of the low birthweights and of the genesis of pre-term and small for date babies. A correlation between nutritional status and malarial infection was shown. According to IgM concentrations in cord blood, 2.5% of newborns had an intrauterine infection of unknown origin."}
{"id": "PMID:215577", "title": "A year of deliveries at the Adjam\u00e9 maternity hospital in Abidjan (Ivory Coast).", "content": "This study based on hospital records is an analysis of 7433 deliveries in Adjam\u00e9 Maternity Hospital, Abidjan, Ivory Coast. The incidence of low birthweight babies is 14.1%. Mean birthweight and height were shown to increase significantly from parity 1 to 9. Lowest mean birthweight and highest incidence of low birthweight babies were observed in primiparae. Incidence of stillbirths and abortions according to parity are described and an estimate of infant mortality rate has been attempted.", "contents": "A year of deliveries at the Adjam\u00e9 maternity hospital in Abidjan (Ivory Coast). This study based on hospital records is an analysis of 7433 deliveries in Adjam\u00e9 Maternity Hospital, Abidjan, Ivory Coast. The incidence of low birthweight babies is 14.1%. Mean birthweight and height were shown to increase significantly from parity 1 to 9. Lowest mean birthweight and highest incidence of low birthweight babies were observed in primiparae. Incidence of stillbirths and abortions according to parity are described and an estimate of infant mortality rate has been attempted."}
{"id": "PMID:215578", "title": "Haematological data of African newborns and their mothers in Abidjan.", "content": "The analysis of cord blood samples of 198 African newborns and their mothers confirmed the high prevalence of iron deficiency. A hypochromia and microcytosis of red cells was found in 40% of the pregnant women at term. In the majority of newborns the haemoglobin concentration was below 16 g/100 ml. Hb S was found in 11%, Hb C in 9% and alpha-thalassaemia in 2% of the population examined. Haemoglobin, packed cell volume and mean cell volume of erythrocytes were lower than results of newborns from developed countries. Foetal sex had no influence on haematological variables.", "contents": "Haematological data of African newborns and their mothers in Abidjan. The analysis of cord blood samples of 198 African newborns and their mothers confirmed the high prevalence of iron deficiency. A hypochromia and microcytosis of red cells was found in 40% of the pregnant women at term. In the majority of newborns the haemoglobin concentration was below 16 g/100 ml. Hb S was found in 11%, Hb C in 9% and alpha-thalassaemia in 2% of the population examined. Haemoglobin, packed cell volume and mean cell volume of erythrocytes were lower than results of newborns from developed countries. Foetal sex had no influence on haematological variables."}
{"id": "PMID:215579", "title": "Enzyme histochemical properties of kitten osteoclasts in bone imprint preparations.", "content": "The enzyme histochemical characteristics of osteoclasts in imprints of the metaphyseal regions of femurs, from male kittens aged approximately 18 weeks, were investigated. A selected number of enzymes representative of a variety of metabolic pathways were studied. The enzyme profile, time for the first appearance of detectable reaction product, intensity of the reactions, and localization of the reaction products were noted. Osteoclasts are rich in enzymes, and metabolic pathways are well developed in respect of the utilization of the reduced coenzymes NADP and NADPH, succinic, malic, lactic, and isocitric acids, beta-hydroxybutyrate and glucose-6-phosphate, the reactions being mediated by the diaphorases and dehydrogenases. The activities of acid and neutral phosphatases, non-specific esterases, and leucine naphthylamidase were high in these cells. However, little or no activity was demonstrated in respect of glutamate and alpha-glycerophosphate dehydrogenases or of aryl sulphatase, glucose-6-phosphatase and alkaline phosphatase.", "contents": "Enzyme histochemical properties of kitten osteoclasts in bone imprint preparations. The enzyme histochemical characteristics of osteoclasts in imprints of the metaphyseal regions of femurs, from male kittens aged approximately 18 weeks, were investigated. A selected number of enzymes representative of a variety of metabolic pathways were studied. The enzyme profile, time for the first appearance of detectable reaction product, intensity of the reactions, and localization of the reaction products were noted. Osteoclasts are rich in enzymes, and metabolic pathways are well developed in respect of the utilization of the reduced coenzymes NADP and NADPH, succinic, malic, lactic, and isocitric acids, beta-hydroxybutyrate and glucose-6-phosphate, the reactions being mediated by the diaphorases and dehydrogenases. The activities of acid and neutral phosphatases, non-specific esterases, and leucine naphthylamidase were high in these cells. However, little or no activity was demonstrated in respect of glutamate and alpha-glycerophosphate dehydrogenases or of aryl sulphatase, glucose-6-phosphatase and alkaline phosphatase."}
{"id": "PMID:215580", "title": "Ultrastructural localization of glycogen in the granulocytes of normal rabbit bone marrow.", "content": "The glycogen of rabbit granulocytes has been studied in glutaraldehyde and osmium tetroxide fixed bone marrow by the periodic acid-thiocarbohydrazide-silver proteinate procedure (PA-TCH-SP). The PA-TCH-SP procedure involved the staining of intracytoplasmic glycogen more densely than the routine lead citrate staining. The PA-TCH-SP procedure demonstrated the intracytoplasmic glycogen in all three kinds of granulocytes. Though a sequence of intensity was observed in each stage of cell maturation, intracytoplasmic glycogen increased generally in accordance with cell maturation in the granulocytes. Functional significance of the glycogen in the granulocytes was discussed in relation to its staining. A very weak reaction in the granules of the granulocytes was described in relation to their contents.", "contents": "Ultrastructural localization of glycogen in the granulocytes of normal rabbit bone marrow. The glycogen of rabbit granulocytes has been studied in glutaraldehyde and osmium tetroxide fixed bone marrow by the periodic acid-thiocarbohydrazide-silver proteinate procedure (PA-TCH-SP). The PA-TCH-SP procedure involved the staining of intracytoplasmic glycogen more densely than the routine lead citrate staining. The PA-TCH-SP procedure demonstrated the intracytoplasmic glycogen in all three kinds of granulocytes. Though a sequence of intensity was observed in each stage of cell maturation, intracytoplasmic glycogen increased generally in accordance with cell maturation in the granulocytes. Functional significance of the glycogen in the granulocytes was discussed in relation to its staining. A very weak reaction in the granules of the granulocytes was described in relation to their contents."}
{"id": "PMID:215581", "title": "Histochemical studies of some myocardial oxido-reductive enzymes after experimental beta-adrenergic blockade with propranolol.", "content": "Histochemical studies of some myocardial oxido--reductive enzymes after a beta--adrenergic blockade with propranolol have been carried out. Succinate, isocitrate and glucose-6-phosphate dehydrogenases did not indicate any changes in activity, whereas the changes in reaction intensities concerning NADH and NADPH tetrazole reductases and glutamate dehydrogenase have rather a transitory and reversible character. Only lactate dehydrogenase showed an increase in the enzymatic activity which speaks for an increase in the glycolysis process in the heart muscle. In the light of our own presented research results we assume that the experimental beta--adrenergic blockade of the heart muscle in rats does not evoke more important enzymatic changes which are noticeable in histochemical microscope examination.", "contents": "Histochemical studies of some myocardial oxido-reductive enzymes after experimental beta-adrenergic blockade with propranolol. Histochemical studies of some myocardial oxido--reductive enzymes after a beta--adrenergic blockade with propranolol have been carried out. Succinate, isocitrate and glucose-6-phosphate dehydrogenases did not indicate any changes in activity, whereas the changes in reaction intensities concerning NADH and NADPH tetrazole reductases and glutamate dehydrogenase have rather a transitory and reversible character. Only lactate dehydrogenase showed an increase in the enzymatic activity which speaks for an increase in the glycolysis process in the heart muscle. In the light of our own presented research results we assume that the experimental beta--adrenergic blockade of the heart muscle in rats does not evoke more important enzymatic changes which are noticeable in histochemical microscope examination."}
{"id": "PMID:215583", "title": "Waking and ventilatory responses to laryngeal stimulation in sleeping dogs.", "content": "We studied waking and ventilatory responses to laryngeal stimulation during sleep in three dogs. The dogs breathed through an endotracheal tube inserted caudally into the trachea through a tracheostomy. Laryngeal stimulation was produced either by inflating a small balloon that was positioned in the rostral tracheal segment, or by squirting water onto the larynx through a catheter inserted through the tracheostomy. Airflow was measured with a pneumotachograph, and sleep state was determined by behavioral, electroencephalographic, and electromyographic criteria. We found that the degree of laryngeal stimulation required to produce arousal and coughing was higher in rapid-eye-movement (REM) sleep than in slow-wave sleep (SWS). Stimuli that failed to cause arousal from SWS often produced a single expiratory effort, or brief apnea (1--2 s) and bradycardia. In contrast, during REM sleep subarousal stimuli often resulted in prolonged apnea (greater than 10 s) and marked bradycardia. We conclude that during REM sleep arousal responses to laryngeal stimulation are depressed, but ventilatory and cardiac responses are intact.", "contents": "Waking and ventilatory responses to laryngeal stimulation in sleeping dogs. We studied waking and ventilatory responses to laryngeal stimulation during sleep in three dogs. The dogs breathed through an endotracheal tube inserted caudally into the trachea through a tracheostomy. Laryngeal stimulation was produced either by inflating a small balloon that was positioned in the rostral tracheal segment, or by squirting water onto the larynx through a catheter inserted through the tracheostomy. Airflow was measured with a pneumotachograph, and sleep state was determined by behavioral, electroencephalographic, and electromyographic criteria. We found that the degree of laryngeal stimulation required to produce arousal and coughing was higher in rapid-eye-movement (REM) sleep than in slow-wave sleep (SWS). Stimuli that failed to cause arousal from SWS often produced a single expiratory effort, or brief apnea (1--2 s) and bradycardia. In contrast, during REM sleep subarousal stimuli often resulted in prolonged apnea (greater than 10 s) and marked bradycardia. We conclude that during REM sleep arousal responses to laryngeal stimulation are depressed, but ventilatory and cardiac responses are intact."}
{"id": "PMID:215584", "title": "O2 uptake and developed tension during and after fatigue, curare block, and ischemia.", "content": "The purpose of this study was to investigate the effect of changes in developed tension on the ratio between O2 uptake and isometric developed tension in the in situ dog gastrocnemius-plantaris muscle group. O2 uptake and isometric developed tension of the muscle were measured during contractions at 1 twitch/s before and after fatigue with both single and twin impulses (6.5 V, 0.2-ms duration; the twins were separated by 10--20 ms). Twin impulses prior to fatigue raised developed tension to two times the tension developed with single impulses. Fatigue was obtained by stimulation at 10--20 impulses/s for 30--40 min. Twin impulses after fatigue returned developed tension to the level of single impulses before fatigue. O2 uptake and developed tension were also measured during the slower development of fatigue produced by continuous stimulation (3, 4, 5, and 6 impulses/s) as well as during \"fatigue\" induced by partial neuromuscular block with curare or ischemia. In all cases, there was no change in the O2 uptake per unit of tension developed, indicating a constant coupling between O2 uptake and developed tension.", "contents": "O2 uptake and developed tension during and after fatigue, curare block, and ischemia. The purpose of this study was to investigate the effect of changes in developed tension on the ratio between O2 uptake and isometric developed tension in the in situ dog gastrocnemius-plantaris muscle group. O2 uptake and isometric developed tension of the muscle were measured during contractions at 1 twitch/s before and after fatigue with both single and twin impulses (6.5 V, 0.2-ms duration; the twins were separated by 10--20 ms). Twin impulses prior to fatigue raised developed tension to two times the tension developed with single impulses. Fatigue was obtained by stimulation at 10--20 impulses/s for 30--40 min. Twin impulses after fatigue returned developed tension to the level of single impulses before fatigue. O2 uptake and developed tension were also measured during the slower development of fatigue produced by continuous stimulation (3, 4, 5, and 6 impulses/s) as well as during \"fatigue\" induced by partial neuromuscular block with curare or ischemia. In all cases, there was no change in the O2 uptake per unit of tension developed, indicating a constant coupling between O2 uptake and developed tension."}
{"id": "PMID:215585", "title": "Effect of exercise on collateral development in dogs with normal coronary arteries.", "content": "To determine the effects of chronic exercise on the coronary collateral circulation of dogs with normal coronary arteries, 1-yr-old purebred beagles were divided into sedentary control and exercising groups. The latter were trained to run on a treadmill. A lower maximal heart rate during a standardized exercise test protocol after a 10- to 12-week training period and a higher gastrocnemius cytochrome oxidase activity in the runners attested to the presence of cardiovascular and skeletal muscle training effects. However, left ventricular weights, left ventricle/body weight ratios, myocardial myofibrillar and myosin ATPases, and hemodynamics were similar in sedentary and exercising dogs except for a significantly higher resting cardiac output in the runners. After occlusion of the left anterior descending coronary artery, both collateral conductance (retrograde flow/aortic pressure) and collateral flow measured with microspheres tended to be lower in the trained dogs, but differences were not significant. The endocardial/epicardial flow ratio in the ischemic area after coronary occlusion did not distinguish between exercisers and controls. Thus treadmill running in the dog with normal coronary arteries produced a training effect, but had no effect on coronary collateral vessels.", "contents": "Effect of exercise on collateral development in dogs with normal coronary arteries. To determine the effects of chronic exercise on the coronary collateral circulation of dogs with normal coronary arteries, 1-yr-old purebred beagles were divided into sedentary control and exercising groups. The latter were trained to run on a treadmill. A lower maximal heart rate during a standardized exercise test protocol after a 10- to 12-week training period and a higher gastrocnemius cytochrome oxidase activity in the runners attested to the presence of cardiovascular and skeletal muscle training effects. However, left ventricular weights, left ventricle/body weight ratios, myocardial myofibrillar and myosin ATPases, and hemodynamics were similar in sedentary and exercising dogs except for a significantly higher resting cardiac output in the runners. After occlusion of the left anterior descending coronary artery, both collateral conductance (retrograde flow/aortic pressure) and collateral flow measured with microspheres tended to be lower in the trained dogs, but differences were not significant. The endocardial/epicardial flow ratio in the ischemic area after coronary occlusion did not distinguish between exercisers and controls. Thus treadmill running in the dog with normal coronary arteries produced a training effect, but had no effect on coronary collateral vessels."}
{"id": "PMID:215586", "title": "Triiodothyronine (T3) concentration and therapy in autistic children.", "content": "The clinical and biochemical status of thyroid function of patients with an autistic syndrome was investigated. The study consisted of 13 patients between the ages of 7 and 21 years. There was no clinical evidence for hypothyroidism in any patient, and T3, T4, and TSH concentrations were within the normal range. Two patients who had retarded bone ages were treated with triiodothyronine for 6 months. Hyperthyroidism developed when T3 levels exceeded physiologic concentrations in these patients. The concept that the clinical response to triiodothyronine in autistic patients results from correction of thyroid dysfunction is not supported by these findings.", "contents": "Triiodothyronine (T3) concentration and therapy in autistic children. The clinical and biochemical status of thyroid function of patients with an autistic syndrome was investigated. The study consisted of 13 patients between the ages of 7 and 21 years. There was no clinical evidence for hypothyroidism in any patient, and T3, T4, and TSH concentrations were within the normal range. Two patients who had retarded bone ages were treated with triiodothyronine for 6 months. Hyperthyroidism developed when T3 levels exceeded physiologic concentrations in these patients. The concept that the clinical response to triiodothyronine in autistic patients results from correction of thyroid dysfunction is not supported by these findings."}
{"id": "PMID:215591", "title": "Mode of inhibition of globin synthesis by m7G5'p and m7G5'ppp.", "content": "The mode of inhibition of rabbit globin synthesis by m7G5'p and m7G5'ppp (\"cap analogs\") was studied using the rabbit reticulocyte lysate system. The rate of globin synthesis was measured at various concentrations of both f[35S]Met-tRNAf and the cap analogs. The cap analogs were found to inhibit competitively the incorporation of f[35S]Met into hot trichloroacetic acid-insoluble material. Nascent chains prelabelled with f[35S]Met were released at various concentrations of m7G5'ppp. The release of nascent chains was not inhibited by m7G5'p (Suzuki, H. (1976) FEBS Lett. 72, 309) and m7G5'ppp, and it is therefore concluded that the cap analogs inhibit a step of initiation of globin synthesis. Under conditions such that the elongation of nascent chains was inhibited by sparsomycin, the formation of an 80S/fMet-tRNAf was inhibited by the cap analogs, but not that of a 40S/fMet-tRNAf complex. These data suggest that a factor which is required for the binding of globin mRNA with 40S/fMet-tRNAf complex forms an inactive complex with the cap analogs, so that the cap analogs inhibit globin synthesis.", "contents": "Mode of inhibition of globin synthesis by m7G5'p and m7G5'ppp. The mode of inhibition of rabbit globin synthesis by m7G5'p and m7G5'ppp (\"cap analogs\") was studied using the rabbit reticulocyte lysate system. The rate of globin synthesis was measured at various concentrations of both f[35S]Met-tRNAf and the cap analogs. The cap analogs were found to inhibit competitively the incorporation of f[35S]Met into hot trichloroacetic acid-insoluble material. Nascent chains prelabelled with f[35S]Met were released at various concentrations of m7G5'ppp. The release of nascent chains was not inhibited by m7G5'p (Suzuki, H. (1976) FEBS Lett. 72, 309) and m7G5'ppp, and it is therefore concluded that the cap analogs inhibit a step of initiation of globin synthesis. Under conditions such that the elongation of nascent chains was inhibited by sparsomycin, the formation of an 80S/fMet-tRNAf was inhibited by the cap analogs, but not that of a 40S/fMet-tRNAf complex. These data suggest that a factor which is required for the binding of globin mRNA with 40S/fMet-tRNAf complex forms an inactive complex with the cap analogs, so that the cap analogs inhibit globin synthesis."}
{"id": "PMID:215592", "title": "Collagenolytic activities of cultured human malignant melanoma cells.", "content": "Three human malignant melanomas were cultured in pure populations and one tumor was cloned into melanotic and amelanotic cell lines. In the homogenates of these cultured cells, specific collagenase activities were demonstrated by isotope release from 14C-labeled collagen, disc electrophoresis, and specific cleavage of collagen molecules as demonstrated in the segment long spacing form. No significant collagenase activity was observed in the culture media. Interestingly, early cultures had a high collagenase activity in the cells and as they were successively subcultured, the activity diminished. Cysteine completely inhibited the degradation of tropocollagen as determined by disc electrophoresis and EDTA partially inhibited the degradation. It is concluded that human malignant melanoma cells produce a specific collagenase in vitro which can be extracted in early culture directly from the homogenate.", "contents": "Collagenolytic activities of cultured human malignant melanoma cells. Three human malignant melanomas were cultured in pure populations and one tumor was cloned into melanotic and amelanotic cell lines. In the homogenates of these cultured cells, specific collagenase activities were demonstrated by isotope release from 14C-labeled collagen, disc electrophoresis, and specific cleavage of collagen molecules as demonstrated in the segment long spacing form. No significant collagenase activity was observed in the culture media. Interestingly, early cultures had a high collagenase activity in the cells and as they were successively subcultured, the activity diminished. Cysteine completely inhibited the degradation of tropocollagen as determined by disc electrophoresis and EDTA partially inhibited the degradation. It is concluded that human malignant melanoma cells produce a specific collagenase in vitro which can be extracted in early culture directly from the homogenate."}
{"id": "PMID:215593", "title": "Acyl-Coenzyme A synthetase and fatty acid oxidation in rat liver peroxisomes.", "content": "Rat liver peroxisomes oxidized palmitate in the presence of ATP, CoA and NAD+, and the rate of palmitate oxidation exceeded that of palmitoyl-CoA oxidation. Acyl-CoA synthetase [acid: CoA ligase (AMP-forming); EC 6.2.1.3] was found in peroxisomes. The substrate specificity of the peroxisomal synthetase towards fatty acids with various carbon chain lengths was similar to that of the microsomal enzyme. The peroxisomal synthetase activity toward palmitate (40--100 nmol/min per mg protein) was higher than the rate of palmitate oxidation by the peroxisomal system (0.7--1.7 nmol/min per mg protein). The data show that peroxisomes activate long chain fatty acids and oxidize their acyl-CoA derivatives.", "contents": "Acyl-Coenzyme A synthetase and fatty acid oxidation in rat liver peroxisomes. Rat liver peroxisomes oxidized palmitate in the presence of ATP, CoA and NAD+, and the rate of palmitate oxidation exceeded that of palmitoyl-CoA oxidation. Acyl-CoA synthetase [acid: CoA ligase (AMP-forming); EC 6.2.1.3] was found in peroxisomes. The substrate specificity of the peroxisomal synthetase towards fatty acids with various carbon chain lengths was similar to that of the microsomal enzyme. The peroxisomal synthetase activity toward palmitate (40--100 nmol/min per mg protein) was higher than the rate of palmitate oxidation by the peroxisomal system (0.7--1.7 nmol/min per mg protein). The data show that peroxisomes activate long chain fatty acids and oxidize their acyl-CoA derivatives."}
{"id": "PMID:215595", "title": "Primary avian tendon cells in culture. An improved system for understanding malignant transformation.", "content": "Primary avian tendon (PAT) cells which maintain their differentiated state in culture are rapidly transformed by Rous sarcoma virus. By criteria of morphology, increased rate of 2-deoxyglucose uptake, and loss of density dependent growth control, PAT cells transform as well as their less differentiated counterpart, chick embryo fibroblasts. In addition, the percentage of collagen produced by PAT cells drops on transformation by an order of magnitude, from 23 to 2.5%, but is unaffected by viral replication of a transformation-defective mutant. The responsiveness of normal and transformed PAT cells to various environmental factors changes dramatically upon transformation. Normal PAT cells respond to the presence of ascorbate and high cell density by raising the level of collagen synthesis from 5 to 23%. Transformed PAT cells are totally unresponsive. These and previously reported results lead us to postulate that the break-down in the normal regulatory mechanisms used by the cell to maintain the differentiated state is related to or is responsible for the onset of malignant transformation.", "contents": "Primary avian tendon cells in culture. An improved system for understanding malignant transformation. Primary avian tendon (PAT) cells which maintain their differentiated state in culture are rapidly transformed by Rous sarcoma virus. By criteria of morphology, increased rate of 2-deoxyglucose uptake, and loss of density dependent growth control, PAT cells transform as well as their less differentiated counterpart, chick embryo fibroblasts. In addition, the percentage of collagen produced by PAT cells drops on transformation by an order of magnitude, from 23 to 2.5%, but is unaffected by viral replication of a transformation-defective mutant. The responsiveness of normal and transformed PAT cells to various environmental factors changes dramatically upon transformation. Normal PAT cells respond to the presence of ascorbate and high cell density by raising the level of collagen synthesis from 5 to 23%. Transformed PAT cells are totally unresponsive. These and previously reported results lead us to postulate that the break-down in the normal regulatory mechanisms used by the cell to maintain the differentiated state is related to or is responsible for the onset of malignant transformation."}
{"id": "PMID:215596", "title": "Transport and phosphorylation of hexoses in normal and Rous sarcoma virus-transformed chick embryo fibroblasts.", "content": "Effects of transformation by Rous sarcoma virus on sugar uptake and activity and the subcellular distribution of hexokinase isozymes in chick embryo fibroblasts were examined. Transformation caused a several-fold increase in the maximum velocity for uptake of 2-deoxyglucose without a significant change in Km. Cytochalasin B (CB), was used to differentiate between the effects of transformation on facilitated diffusion and the nonsaturable (CB-insensitive) mode. Transformation was found to stimulate 2-deoxyglucose transport by both mechanisms, but the increase in transport by the CB-insensitive mode was greater. Transformation enhances the activity of hexokinase, the enhancement being confined to the particulate fraction of the enzyme. Heat-inactivation and electrophoretic mobility studies showed that although hexokinase Type I is the major form in both normal and transformed fibroblasts, there is a significant increase in the proportion of the Type II isozyme in the transformed cells.", "contents": "Transport and phosphorylation of hexoses in normal and Rous sarcoma virus-transformed chick embryo fibroblasts. Effects of transformation by Rous sarcoma virus on sugar uptake and activity and the subcellular distribution of hexokinase isozymes in chick embryo fibroblasts were examined. Transformation caused a several-fold increase in the maximum velocity for uptake of 2-deoxyglucose without a significant change in Km. Cytochalasin B (CB), was used to differentiate between the effects of transformation on facilitated diffusion and the nonsaturable (CB-insensitive) mode. Transformation was found to stimulate 2-deoxyglucose transport by both mechanisms, but the increase in transport by the CB-insensitive mode was greater. Transformation enhances the activity of hexokinase, the enhancement being confined to the particulate fraction of the enzyme. Heat-inactivation and electrophoretic mobility studies showed that although hexokinase Type I is the major form in both normal and transformed fibroblasts, there is a significant increase in the proportion of the Type II isozyme in the transformed cells."}
{"id": "PMID:215598", "title": "Measurements of metabolites during cAMP oscillations of Dictyostelium discoideum.", "content": "During aggregation the cellular slime mold Dictyostelium discoideum synthesizes and releases pulses of cAMP about every five minutes. Current models proposed to explain this phenomenon postulate that oscillating levels of some key intracellular metabolite control the oscillatory synthesis of cAMP. We have assayed the levels of likely candidates for this metabolite during a cAMP oscillation, but have found them to remain constant. Compounds measured include ATP, GTP, glucose-1-phosphate, glucose-6-phosphate, isocitrate, alpha-ketoglutarate, amino acids, and other aminated metabolites. On the basis of this negative data, as well as results described elsewhere (Geller and Brenner, '78), we question whether the proposed models are correct, and discuss several alternatives.", "contents": "Measurements of metabolites during cAMP oscillations of Dictyostelium discoideum. During aggregation the cellular slime mold Dictyostelium discoideum synthesizes and releases pulses of cAMP about every five minutes. Current models proposed to explain this phenomenon postulate that oscillating levels of some key intracellular metabolite control the oscillatory synthesis of cAMP. We have assayed the levels of likely candidates for this metabolite during a cAMP oscillation, but have found them to remain constant. Compounds measured include ATP, GTP, glucose-1-phosphate, glucose-6-phosphate, isocitrate, alpha-ketoglutarate, amino acids, and other aminated metabolites. On the basis of this negative data, as well as results described elsewhere (Geller and Brenner, '78), we question whether the proposed models are correct, and discuss several alternatives."}
{"id": "PMID:215600", "title": "Synergistic hemolysis phenomenon shown by an alpha-toxin-producing Clostridium perfingens and streptococcal CAMP factor in presumptive streptococcal grouping.", "content": "A new phenomenon of synergistic hemolysis by Clostridium perfringens alpha-toxin and the streptococcal CAMP factor on human and guinea pig erythrocytes is described. A possible mode of action of the CAMP factors is suggested. On human blood agar all of the tested isolates of group B streptococci gave an arrowhead-shaped zone of hemolysis; 74% of group A gave a crescent-shaped lytic zone, whereas all isolates of groups C and G and the remaining 26% of group A streptococci gave a bullet-shaped lytic zone. By comparison, in the CAMP test incubated aerobically and anaerobically, 70 and 91%, respectively, of streptococci other than group B gave positive, arrowhead-shaped lytic zones. If all intermediate positive reactions in the CAMP tests were read as negative after aerobic incubation, only 89% of group B streptococci would be properly identified. The synergistic hemolysis phenomenon, using an alpha-toxin-producing C. perfringens and human blood agar, provided a reliable test for presumptive identification of group B streptococci, with promising potential to differentiate in the same test group A streptococci from other groups.", "contents": "Synergistic hemolysis phenomenon shown by an alpha-toxin-producing Clostridium perfingens and streptococcal CAMP factor in presumptive streptococcal grouping. A new phenomenon of synergistic hemolysis by Clostridium perfringens alpha-toxin and the streptococcal CAMP factor on human and guinea pig erythrocytes is described. A possible mode of action of the CAMP factors is suggested. On human blood agar all of the tested isolates of group B streptococci gave an arrowhead-shaped zone of hemolysis; 74% of group A gave a crescent-shaped lytic zone, whereas all isolates of groups C and G and the remaining 26% of group A streptococci gave a bullet-shaped lytic zone. By comparison, in the CAMP test incubated aerobically and anaerobically, 70 and 91%, respectively, of streptococci other than group B gave positive, arrowhead-shaped lytic zones. If all intermediate positive reactions in the CAMP tests were read as negative after aerobic incubation, only 89% of group B streptococci would be properly identified. The synergistic hemolysis phenomenon, using an alpha-toxin-producing C. perfringens and human blood agar, provided a reliable test for presumptive identification of group B streptococci, with promising potential to differentiate in the same test group A streptococci from other groups."}
{"id": "PMID:215601", "title": "Method for evaluating broth culture media: application to Haemophilus.", "content": "A method was devised to test the growth-promoting ability of a broth medium. The \"dilute to extinction\" method determines the inoculum required to develop heavy turbidity in a broth with overnight incubation. A statistical method using Poisson distribution was used to show that a single Haemophilus cell can develop heavy turbidity in an optimal broth. The dilute to extinction method was used to evaluate the shelf life of stored media, to titrate the growth factor requirements of Haemophilus, and to evaluate the use of purified hemin and nicotinamide adenine dinucleotide in a broth medium for the growth of Haemophilus. Of the media tested, the most suitable formulation was Mueller-Hinton broth supplemented with 10 microgram of hemin and 10 microgram of nicotinamide adenine dinucleotide per ml. The dilute to extinction method appears to be especially useful in the development of broth media for fastidious organisms. The method could also be used to assure the quality of other broth media which are required to support the growth of small inocula in the clinical or research laboratory.", "contents": "Method for evaluating broth culture media: application to Haemophilus. A method was devised to test the growth-promoting ability of a broth medium. The \"dilute to extinction\" method determines the inoculum required to develop heavy turbidity in a broth with overnight incubation. A statistical method using Poisson distribution was used to show that a single Haemophilus cell can develop heavy turbidity in an optimal broth. The dilute to extinction method was used to evaluate the shelf life of stored media, to titrate the growth factor requirements of Haemophilus, and to evaluate the use of purified hemin and nicotinamide adenine dinucleotide in a broth medium for the growth of Haemophilus. Of the media tested, the most suitable formulation was Mueller-Hinton broth supplemented with 10 microgram of hemin and 10 microgram of nicotinamide adenine dinucleotide per ml. The dilute to extinction method appears to be especially useful in the development of broth media for fastidious organisms. The method could also be used to assure the quality of other broth media which are required to support the growth of small inocula in the clinical or research laboratory."}
{"id": "PMID:215602", "title": "Antibody assays for varicella-zoster virus: comparison of enzyme immunoassay with neutralization, immune adherence hemagglutination, and complement fixation.", "content": "An enzyme immunossay (EIA) was adapted for detection of antibody to varicella-zoster virus, and its sensitivity and specificity were compared with those of neutralization, immune adherence hemagglutination (IAHA), and complement fixation tests. Test sera showed little nonspecific reactivity in the EIA system, and valid results could usually be obtained at serum dilutions as low as 1:8. Demonstration of the presence or absence of varicella-zoster viral antibody by EIA showed 94% correlation with results obtained in neutralization tests, but EIA titers were 2- to 16-fold higher than neutralizing antibody titers. Results by IAHA showed 87% correlation with those obtained by neutralization. No false positive IAHA results were seen, but a number of false negative IAHA results were seen at the 1:8 serum dilution, particularly in older individuals. With increasing age (>40 years), and presumably increased time from varicella infection, neutralizing antibody levels generally declined to 1:8 or 1:16, EIA levels fell to 1:128 or 1:256, and IAHA and complement fixation antibody titers were usually <1:8 or 1:8. EIA and IAHA were as reliable as the neutralization and complement fixation tests for serodiagnosis of varicella and zoster infections. All tests demonstrated heterotypic varicella-zoster antibody titer rises in selected patients with initial herpes simplex virus infections, but fewer heterotypic responses were seen by EIA than by the other methods. EIA offers a rapid, sensitive, and specific method for varicella-zoster antibody assay that is applicable to use in a clinical setting.", "contents": "Antibody assays for varicella-zoster virus: comparison of enzyme immunoassay with neutralization, immune adherence hemagglutination, and complement fixation. An enzyme immunossay (EIA) was adapted for detection of antibody to varicella-zoster virus, and its sensitivity and specificity were compared with those of neutralization, immune adherence hemagglutination (IAHA), and complement fixation tests. Test sera showed little nonspecific reactivity in the EIA system, and valid results could usually be obtained at serum dilutions as low as 1:8. Demonstration of the presence or absence of varicella-zoster viral antibody by EIA showed 94% correlation with results obtained in neutralization tests, but EIA titers were 2- to 16-fold higher than neutralizing antibody titers. Results by IAHA showed 87% correlation with those obtained by neutralization. No false positive IAHA results were seen, but a number of false negative IAHA results were seen at the 1:8 serum dilution, particularly in older individuals. With increasing age (>40 years), and presumably increased time from varicella infection, neutralizing antibody levels generally declined to 1:8 or 1:16, EIA levels fell to 1:128 or 1:256, and IAHA and complement fixation antibody titers were usually <1:8 or 1:8. EIA and IAHA were as reliable as the neutralization and complement fixation tests for serodiagnosis of varicella and zoster infections. All tests demonstrated heterotypic varicella-zoster antibody titer rises in selected patients with initial herpes simplex virus infections, but fewer heterotypic responses were seen by EIA than by the other methods. EIA offers a rapid, sensitive, and specific method for varicella-zoster antibody assay that is applicable to use in a clinical setting."}
{"id": "PMID:215603", "title": "Comparison of pseudorabies virus inactivated by bromo-ethylene-imine, 60Co irradiation, and acridine dye in immune assay systems.", "content": "Pseudorabies virus infections among animals, especially swine, have become prevalent in the United States in the past few years. The disease in swine is now economically important. Test systems and antigens are being developed for use in control and disease suppression efforts. Pseudorabies virus was inactivated by three methods: chemically, with bromo-ethylene-imine; physically, with 60Co irradiation; and chemically and physically, with 3,9-diaminoacridine dye followed by exposure to white visible light. The antigenicities of the preparations were determined in the presence of specific antibody in immunodiffusion tests and through immunoelectrophoresis. The latter technique permitted quantitation of either antigen or antibody. In the electrophoretic patterns, the antigenic mass in bromo-ethylene-imine preparations was estimated to be 42 mg/ml, the same as in the untreated control material. After 60Co irradiation, 22 mg/ml was present, in comparison with 50 mg/ml in the untreated control antigen. In contrast, 67 mg/ml was present in the acridine dye-light-treated preparation, in comparison with 58 mg/ml in the untreated control material. A possible explanation for the acridine dye-light-treated preparation values is that photodynamic inactivation interferes with viral maturation during the replicative cycle within cells, with a resulting production of a greater amount of antigen, at least some of which is in the form of defective particles.", "contents": "Comparison of pseudorabies virus inactivated by bromo-ethylene-imine, 60Co irradiation, and acridine dye in immune assay systems. Pseudorabies virus infections among animals, especially swine, have become prevalent in the United States in the past few years. The disease in swine is now economically important. Test systems and antigens are being developed for use in control and disease suppression efforts. Pseudorabies virus was inactivated by three methods: chemically, with bromo-ethylene-imine; physically, with 60Co irradiation; and chemically and physically, with 3,9-diaminoacridine dye followed by exposure to white visible light. The antigenicities of the preparations were determined in the presence of specific antibody in immunodiffusion tests and through immunoelectrophoresis. The latter technique permitted quantitation of either antigen or antibody. In the electrophoretic patterns, the antigenic mass in bromo-ethylene-imine preparations was estimated to be 42 mg/ml, the same as in the untreated control material. After 60Co irradiation, 22 mg/ml was present, in comparison with 50 mg/ml in the untreated control antigen. In contrast, 67 mg/ml was present in the acridine dye-light-treated preparation, in comparison with 58 mg/ml in the untreated control material. A possible explanation for the acridine dye-light-treated preparation values is that photodynamic inactivation interferes with viral maturation during the replicative cycle within cells, with a resulting production of a greater amount of antigen, at least some of which is in the form of defective particles."}
{"id": "PMID:215604", "title": "Trophoblastic disease with coexistent fetus: a sonographic and clinical spectrum.", "content": "The sonographic and clinical spectrum of coexistent live fetus and trophoblastic disease is illustrated and discussed. Two patients with a single placenta with trophoblastic change and one patient with two placentas, one normal and one with a hydatidiform mole, are described. The clinical and sonographic abnormalities in all three patients were characteristic. In the two patients with single placenta, the histologic findings were minimal. The clinical and sonographic presentations of coexistent mole and fetus are described and etiology is discussed. The implication of the lack of histologic confirmation of hydatidiform mole suggests a spectrum of findings in trophoblastic disease.", "contents": "Trophoblastic disease with coexistent fetus: a sonographic and clinical spectrum. The sonographic and clinical spectrum of coexistent live fetus and trophoblastic disease is illustrated and discussed. Two patients with a single placenta with trophoblastic change and one patient with two placentas, one normal and one with a hydatidiform mole, are described. The clinical and sonographic abnormalities in all three patients were characteristic. In the two patients with single placenta, the histologic findings were minimal. The clinical and sonographic presentations of coexistent mole and fetus are described and etiology is discussed. The implication of the lack of histologic confirmation of hydatidiform mole suggests a spectrum of findings in trophoblastic disease."}
{"id": "PMID:215605", "title": "Ultrasonographic demonstration of inferior vena caval invasion.", "content": "Whenever a liver neoplasm is seen ultrasonographically, an effort should be made to visualize the veins within the liver as well as the inferior vena cava for tumor extension. Valuable information can be obtained by the demonstration of this finding which may radically alter the further work-up and treatment of the patient.", "contents": "Ultrasonographic demonstration of inferior vena caval invasion. Whenever a liver neoplasm is seen ultrasonographically, an effort should be made to visualize the veins within the liver as well as the inferior vena cava for tumor extension. Valuable information can be obtained by the demonstration of this finding which may radically alter the further work-up and treatment of the patient."}
{"id": "PMID:215607", "title": "Synaptic fine structure and the termination of corticospinal fibers in the lateral basal region of the cat spinal cord.", "content": "The lateral basal region (LBR) of the spinal cord gray matter (Rexed's laminae IV-VII) by physiologic and anatomic criteria is the major terminal zone for the corticospinal (CS) tract in the cat. The neurons in this area are medium-sized with abundant spines on their dendrites. Axon terminals on the dendrites and somata of these neurons form synapses easily classified as asymmetric with spheroid vesicles and symmetric with flattened vesicles. There are rare exceptions to this. In a systematic count of terminals, 82% have spheroid and 18% flattened vesicles. The majority of all terminals are on dendrites (84.9%) and a minority on somata (14.1%). Less than 1% are axoaxonic. Degeneration of the corticospinal tract was produced by transecting one hemisphere of our experimental cats. Its termination in the lower cervical cord was studied for 17 hours to 7 days after surgery. Vesicle depletion and clumping and dense polymembranous inclusions were the most common forms of degeneration. Filamentous proliferation in the terminals was also prominent; dark degeneration, however, was infrequent. The percent of degenerating CS terminals in the LBR was the following: 17 hours - 2.2%, 36 hours - 4.19%, 2 days - 10.3%, 3 days - 8.4%, 4 days - 6.9%, 7 days - 10.25%; 84.8% of degenerating CS terminals were axodendritic and 15.2% axosomatic.", "contents": "Synaptic fine structure and the termination of corticospinal fibers in the lateral basal region of the cat spinal cord. The lateral basal region (LBR) of the spinal cord gray matter (Rexed's laminae IV-VII) by physiologic and anatomic criteria is the major terminal zone for the corticospinal (CS) tract in the cat. The neurons in this area are medium-sized with abundant spines on their dendrites. Axon terminals on the dendrites and somata of these neurons form synapses easily classified as asymmetric with spheroid vesicles and symmetric with flattened vesicles. There are rare exceptions to this. In a systematic count of terminals, 82% have spheroid and 18% flattened vesicles. The majority of all terminals are on dendrites (84.9%) and a minority on somata (14.1%). Less than 1% are axoaxonic. Degeneration of the corticospinal tract was produced by transecting one hemisphere of our experimental cats. Its termination in the lower cervical cord was studied for 17 hours to 7 days after surgery. Vesicle depletion and clumping and dense polymembranous inclusions were the most common forms of degeneration. Filamentous proliferation in the terminals was also prominent; dark degeneration, however, was infrequent. The percent of degenerating CS terminals in the LBR was the following: 17 hours - 2.2%, 36 hours - 4.19%, 2 days - 10.3%, 3 days - 8.4%, 4 days - 6.9%, 7 days - 10.25%; 84.8% of degenerating CS terminals were axodendritic and 15.2% axosomatic."}
{"id": "PMID:215608", "title": "Membrane-limited granules in sinus hair gelatinous membrane in mice.", "content": "Electron dense membrane limited granules were observed in basal cells of the outer root sheath and in connective tissue sheath of the anagen sinus hair of mice. These granules were oval or round in configuration, and were 150--180 nm in size. They were considered to represent structures related to collagenolytic activity to accelerate elongation of anagen hair.", "contents": "Membrane-limited granules in sinus hair gelatinous membrane in mice. Electron dense membrane limited granules were observed in basal cells of the outer root sheath and in connective tissue sheath of the anagen sinus hair of mice. These granules were oval or round in configuration, and were 150--180 nm in size. They were considered to represent structures related to collagenolytic activity to accelerate elongation of anagen hair."}
{"id": "PMID:215609", "title": "Orogranulocyte peroxidase activity as a measure of inflammatory periodontal disease.", "content": "Benzidine dihydrochloride in the presence of dimethylsulfoxide reacts with myeloperoxidase contained within the granules of polymorphonuclear leukocytes obtained from the oral cavity. A blue meriquinoid oxidation product is formed in the presence of hydrogen peroxide, which can be extracted from the granules with a combination of methyl alcohol and dimethylsulfoxide. A stable yellow-brown pigment is formed which can be measured spectrophotometrically. The values are expressed in optical density units and correlate with the Orogranulocytic Migratory Rate units obtained by other means. Consequently, the spectrophotometric method is an additional non-subjective technique available for the evaluation, monitoring, and indexing the inflammatory periodontal disease.", "contents": "Orogranulocyte peroxidase activity as a measure of inflammatory periodontal disease. Benzidine dihydrochloride in the presence of dimethylsulfoxide reacts with myeloperoxidase contained within the granules of polymorphonuclear leukocytes obtained from the oral cavity. A blue meriquinoid oxidation product is formed in the presence of hydrogen peroxide, which can be extracted from the granules with a combination of methyl alcohol and dimethylsulfoxide. A stable yellow-brown pigment is formed which can be measured spectrophotometrically. The values are expressed in optical density units and correlate with the Orogranulocytic Migratory Rate units obtained by other means. Consequently, the spectrophotometric method is an additional non-subjective technique available for the evaluation, monitoring, and indexing the inflammatory periodontal disease."}
{"id": "PMID:215610", "title": "Angiolymphoid hyperplasia with eosinophilia: report of a case and a review of the literature.", "content": "A case of angiolymphoid hyperplasia with eosinophilia mimicking multiple cylindromas (turban tumor) is presented in detailed clinical and histologic features, and the literature on the condition is reviewed.", "contents": "Angiolymphoid hyperplasia with eosinophilia: report of a case and a review of the literature. A case of angiolymphoid hyperplasia with eosinophilia mimicking multiple cylindromas (turban tumor) is presented in detailed clinical and histologic features, and the literature on the condition is reviewed."}
{"id": "PMID:215612", "title": "The effects of the referral process on hospital in-patients.", "content": "Decisions relating to the preparation for hospital discharge of medical patients can take place at any time after admission to hospital. Referrals to the hospital departments of social work, occupational therapy and physiotherapy, and to community nursing, health visiting and social services are a key factor in this preparation. The referral process is complex and multifaceted and can be analyzed in terms of the questions of who initiates the referral, for what reasons, and at what point in the patient's career. The variant views of role of those professionals involved in the referral process and their perceptions of the situation affect what subsequently takes place and can be examined in relation to each other and to the referral process itself. The complexity may be increased further by the intervention of a patient's relatives. Referrals are made on the basis of a social diagnosis, the sources of information for which are diverse, with the result that the referral process is unstandardized and unpredictable.", "contents": "The effects of the referral process on hospital in-patients. Decisions relating to the preparation for hospital discharge of medical patients can take place at any time after admission to hospital. Referrals to the hospital departments of social work, occupational therapy and physiotherapy, and to community nursing, health visiting and social services are a key factor in this preparation. The referral process is complex and multifaceted and can be analyzed in terms of the questions of who initiates the referral, for what reasons, and at what point in the patient's career. The variant views of role of those professionals involved in the referral process and their perceptions of the situation affect what subsequently takes place and can be examined in relation to each other and to the referral process itself. The complexity may be increased further by the intervention of a patient's relatives. Referrals are made on the basis of a social diagnosis, the sources of information for which are diverse, with the result that the referral process is unstandardized and unpredictable."}
{"id": "PMID:215614", "title": "Paget's disease and the nervous system.", "content": "Paget's disease usually is found in patients past the age of 40. Early presenting symptoms include headache, deafness, tinnitus, and pain due to radicular compression. The diagnosis is confirmed by radiographic features and elevated levels of serum alkaline phosphatase and urinary hydroxyproline. Bony overgrowth results in pressure on nearby soft tissues such as the brain, spinal cord, and certain peripheral nerves. The abnormally soft quality of the calvarial bone permits distortion by the weight of the brain. Dorsal inclination of the plane of the foramen magnum and the projection of the odontoid process into the posterior fossa lead to stretching of the brain stem over the odontoid process and the ventral margin of the foramen. Obstructive hydrocephalus may result. Sarcoma of the crainial vault may develop in cases of Paget's disease. Once cervicomedullary or spinal compression has occurred, surgical decompression may be necessary. Three drugs--calcitonin, disodium etidronate, and mithramycin--have been used with some benefit in the treatment of Paget's disease.", "contents": "Paget's disease and the nervous system. Paget's disease usually is found in patients past the age of 40. Early presenting symptoms include headache, deafness, tinnitus, and pain due to radicular compression. The diagnosis is confirmed by radiographic features and elevated levels of serum alkaline phosphatase and urinary hydroxyproline. Bony overgrowth results in pressure on nearby soft tissues such as the brain, spinal cord, and certain peripheral nerves. The abnormally soft quality of the calvarial bone permits distortion by the weight of the brain. Dorsal inclination of the plane of the foramen magnum and the projection of the odontoid process into the posterior fossa lead to stretching of the brain stem over the odontoid process and the ventral margin of the foramen. Obstructive hydrocephalus may result. Sarcoma of the crainial vault may develop in cases of Paget's disease. Once cervicomedullary or spinal compression has occurred, surgical decompression may be necessary. Three drugs--calcitonin, disodium etidronate, and mithramycin--have been used with some benefit in the treatment of Paget's disease."}
{"id": "PMID:215613", "title": "A review of psychophysiological research with hyperkinetic children.", "content": "A number of studies have appeared which focus on the issue of whether hyperactive children are psychophysiologically different from normal children and what impact the stimulant drugs may have on psychophysiological characteristics of these children. The present paper reviews these studies under the type of measures that were employed. In general, the results suggest that hyperactive children are probably not under- or overaroused in their resting levels of autonomic functions, although some children may display resting cortical underarousal. However, the findings of studies on the impact of stimulation on autonomic or central functions intimate that some hyperactive children are probably underreactive to environmental stimulation, or are \"underarousable.\" Indeed, where differences between hyperactive and normal children are found in such evoked-response studies, they are consistently in this direction of \"underarousability.\" Results for the effects of stimulant drugs suggest that these drugs energize or increase the \"arousal\" of these children and enhance the impact of stimulation on the nervous system. The implications of these results for current theories of hyperactivity and for future research are discussed.", "contents": "A review of psychophysiological research with hyperkinetic children. A number of studies have appeared which focus on the issue of whether hyperactive children are psychophysiologically different from normal children and what impact the stimulant drugs may have on psychophysiological characteristics of these children. The present paper reviews these studies under the type of measures that were employed. In general, the results suggest that hyperactive children are probably not under- or overaroused in their resting levels of autonomic functions, although some children may display resting cortical underarousal. However, the findings of studies on the impact of stimulation on autonomic or central functions intimate that some hyperactive children are probably underreactive to environmental stimulation, or are \"underarousable.\" Indeed, where differences between hyperactive and normal children are found in such evoked-response studies, they are consistently in this direction of \"underarousability.\" Results for the effects of stimulant drugs suggest that these drugs energize or increase the \"arousal\" of these children and enhance the impact of stimulation on the nervous system. The implications of these results for current theories of hyperactivity and for future research are discussed."}
{"id": "PMID:215672", "title": "Cytochemical demonstration of sodium, potassium-adenosine triphosphatase by a hemepeptide derivative of ouabain.", "content": "A cytochemical probe for the ultrastructural localization of the NaKATPase was devised, which utilizes the biological affinity of the noncompetitive inhibitor, ouabain (ouab) to which was coupled a hemepeptide (H11P) which possesses peroxidatic activity. The conjugate, ouab-H11P, had an apparent Ki of approximately 8 x 10(-7) M. When reacted with fixed tissue from the salt gland of osmotically stressed ducklings, the NaKATPase was localized to the basal and lateral infoldings of the plasma membranes of secretory epithelial cells. Reaction product consisted of fine textured deposits distributed in focal patches on the outer aspects of the membrane. Apical membranes were negative, as were intracellular membrane components. Preincubation of tissue with unlabeled ouabain or binding of ouab-H11P in the presence of 10 mM K+, no ATP and no Mg++, resulted in the absence or diminution of reaction product.", "contents": "Cytochemical demonstration of sodium, potassium-adenosine triphosphatase by a hemepeptide derivative of ouabain. A cytochemical probe for the ultrastructural localization of the NaKATPase was devised, which utilizes the biological affinity of the noncompetitive inhibitor, ouabain (ouab) to which was coupled a hemepeptide (H11P) which possesses peroxidatic activity. The conjugate, ouab-H11P, had an apparent Ki of approximately 8 x 10(-7) M. When reacted with fixed tissue from the salt gland of osmotically stressed ducklings, the NaKATPase was localized to the basal and lateral infoldings of the plasma membranes of secretory epithelial cells. Reaction product consisted of fine textured deposits distributed in focal patches on the outer aspects of the membrane. Apical membranes were negative, as were intracellular membrane components. Preincubation of tissue with unlabeled ouabain or binding of ouab-H11P in the presence of 10 mM K+, no ATP and no Mg++, resulted in the absence or diminution of reaction product."}
{"id": "PMID:215673", "title": "Quantitative introduction of a given macromolecule into cells by fusion with erythrocyte ghosts using a fluorescence activated cell sorter.", "content": "FITC-conjugated bovine serum albumin (FITC-BSA) molecules were quantitatively introduced into human erythrocyte ghosts by gradual hemolysis. When the ghosts and L cells were fused with UV-inactivated HVJ (Sendai virus), FITC-BSA was introduced into the cytoplasm of the L cells and fluorescence could be observed inthe cells with a fluorescence microscope. A mixture of L cells and ghosts was introduced into a fluorescence activated cell sorter (FACS), which could separate the mononuclear cells on the basis of their light-scattering profile. Four distinct populations of mononuclear cells were found by fluorescence analysis. These populations were separated from the cell mixture and found to correspond to cells fused with one, two and three ghosts and unfused cells. After separation, the cells from each population could form colonies in culture. As a given macromolecule can be quantitatively introduced into erythrocyte ghosts with the FITC-BSA, after fusion of these ghosts with cells, this sorting method is useful for separating cells containing a definite number of macromolecules.", "contents": "Quantitative introduction of a given macromolecule into cells by fusion with erythrocyte ghosts using a fluorescence activated cell sorter. FITC-conjugated bovine serum albumin (FITC-BSA) molecules were quantitatively introduced into human erythrocyte ghosts by gradual hemolysis. When the ghosts and L cells were fused with UV-inactivated HVJ (Sendai virus), FITC-BSA was introduced into the cytoplasm of the L cells and fluorescence could be observed inthe cells with a fluorescence microscope. A mixture of L cells and ghosts was introduced into a fluorescence activated cell sorter (FACS), which could separate the mononuclear cells on the basis of their light-scattering profile. Four distinct populations of mononuclear cells were found by fluorescence analysis. These populations were separated from the cell mixture and found to correspond to cells fused with one, two and three ghosts and unfused cells. After separation, the cells from each population could form colonies in culture. As a given macromolecule can be quantitatively introduced into erythrocyte ghosts with the FITC-BSA, after fusion of these ghosts with cells, this sorting method is useful for separating cells containing a definite number of macromolecules."}
{"id": "PMID:215674", "title": "The relative effectiveness of commonly used disinfectants in inactivation of coxsackievirus B5.", "content": "Coxsackievirus B5 in the presence of fetal calf serum was exposed to six commonly used disinfectants for times of 10, 20 and 30 s. At the end of exposure times skim milk neutralized the disinfectant activity, with residual virus assayed by the plaque technique. The six disinfectants considered were Javex, sodium hydroxide, ethanol, Wescodyne, One Stroke Ves-Phene and Sonacide. Although 95% (v/v) ethanol was significantly more virucidal than dilutions of the other five disinfectants tested causing a 10(6) reduction in 20 s, it may not be practical to use in many instances. Next to 95% (v/v) ethanol, 1/75 (800 parts/10(6) Javex,  0.25% (w/v) sodium hydroxide and 1/200 Wescodyne were the most effective virucides. These disinfectants were equal in effectiveness causing a 10(5) reduction of coxsackievirus B5 in 30 s. Of these three disinfectants Javex is the most practical to use since sodium hydoroxide is caustic and Wescodyne is selective in its virucidal action. Undiluted Sonacide was a less effective virucide causing a less than 10-fold reduction of coxsackievirus B5 in 30 s. A 1/50 dilution of One Stroke Ves-Phene was the least effective virucide tested since it did not significantly inactivate coxsackievirus B5 in 30 s.", "contents": "The relative effectiveness of commonly used disinfectants in inactivation of coxsackievirus B5. Coxsackievirus B5 in the presence of fetal calf serum was exposed to six commonly used disinfectants for times of 10, 20 and 30 s. At the end of exposure times skim milk neutralized the disinfectant activity, with residual virus assayed by the plaque technique. The six disinfectants considered were Javex, sodium hydroxide, ethanol, Wescodyne, One Stroke Ves-Phene and Sonacide. Although 95% (v/v) ethanol was significantly more virucidal than dilutions of the other five disinfectants tested causing a 10(6) reduction in 20 s, it may not be practical to use in many instances. Next to 95% (v/v) ethanol, 1/75 (800 parts/10(6) Javex,  0.25% (w/v) sodium hydroxide and 1/200 Wescodyne were the most effective virucides. These disinfectants were equal in effectiveness causing a 10(5) reduction of coxsackievirus B5 in 30 s. Of these three disinfectants Javex is the most practical to use since sodium hydoroxide is caustic and Wescodyne is selective in its virucidal action. Undiluted Sonacide was a less effective virucide causing a less than 10-fold reduction of coxsackievirus B5 in 30 s. A 1/50 dilution of One Stroke Ves-Phene was the least effective virucide tested since it did not significantly inactivate coxsackievirus B5 in 30 s."}
{"id": "PMID:215615", "title": "Inherited enzyme variation among JAX strains of domestic rabbits.", "content": "Twelve proteins were assayed for electrophoretic polymorphism in inbred and partially inbred JAX strains of the domestic rabbit. Four enzymes (mannosephosphate isomerase, soluble and mitochondrial malic enzyme, and methemoglobin reductase) were determined to be genetically polymorphic.", "contents": "Inherited enzyme variation among JAX strains of domestic rabbits. Twelve proteins were assayed for electrophoretic polymorphism in inbred and partially inbred JAX strains of the domestic rabbit. Four enzymes (mannosephosphate isomerase, soluble and mitochondrial malic enzyme, and methemoglobin reductase) were determined to be genetically polymorphic."}
{"id": "PMID:215675", "title": "Excretion of foot-and-mouth disease virus in oesophageal-pharyngeal fluid and milk of cattle after intranasal infection.", "content": "The virus growth in the pharyngeal area and the virus excretion in milk of susceptible and vaccinated dairy cows after intranasal instillation of foot-and-mouth disease (FMD) virus type O1 were examined. Ten vaccinated cows were purchased through a market. Of these, nine had delivered their first calf. The cows were inoculated 2-9 months after having received the last dose of vaccine. All vaccinated cows resisted the intranasal challenge. The virus multiplied in the pharyngeal area but, compared with two susceptible controls, to a limited extent. No clear relation was found between virus growth and the titre of circulating neutralizing antibody at the time of challenge. Virus was first detected in milk samples of the susceptible cows when generalized FMD lesions had developed on day four; the excretion lasted for 3-4 days. Up to 19 days after inoculation untreated milk of the vaccinated cows was examined for the presence of infectious FMD virus. Samples were inoculated onto cell cultures, fed to susceptible pigs and calves and injected intramuscularly and/or intradermolingually into susceptible steers. No infectious FMD virus could be detected, either in cell cultures or in susceptible animals. The animals did not develop neutralizing antibody against FMD virus and were subsequently shown to be fully susceptible to challenge. The results are discussed with particular reference to current problems regarding the export of milk products from countries where vaccination against FMD is practised to countries free of the disease.", "contents": "Excretion of foot-and-mouth disease virus in oesophageal-pharyngeal fluid and milk of cattle after intranasal infection. The virus growth in the pharyngeal area and the virus excretion in milk of susceptible and vaccinated dairy cows after intranasal instillation of foot-and-mouth disease (FMD) virus type O1 were examined. Ten vaccinated cows were purchased through a market. Of these, nine had delivered their first calf. The cows were inoculated 2-9 months after having received the last dose of vaccine. All vaccinated cows resisted the intranasal challenge. The virus multiplied in the pharyngeal area but, compared with two susceptible controls, to a limited extent. No clear relation was found between virus growth and the titre of circulating neutralizing antibody at the time of challenge. Virus was first detected in milk samples of the susceptible cows when generalized FMD lesions had developed on day four; the excretion lasted for 3-4 days. Up to 19 days after inoculation untreated milk of the vaccinated cows was examined for the presence of infectious FMD virus. Samples were inoculated onto cell cultures, fed to susceptible pigs and calves and injected intramuscularly and/or intradermolingually into susceptible steers. No infectious FMD virus could be detected, either in cell cultures or in susceptible animals. The animals did not develop neutralizing antibody against FMD virus and were subsequently shown to be fully susceptible to challenge. The results are discussed with particular reference to current problems regarding the export of milk products from countries where vaccination against FMD is practised to countries free of the disease."}
{"id": "PMID:215676", "title": "Immunopathogenicity and oncogenicity of murine leukaemia virus. IV. Antinuclear antibody response and tumour induction in B10.A recombinant mice.", "content": "The levels of murine leukaemia virus (MuLV) proteins p30 and gp70, antinuclear antibody (ANA), anti-soluble nuclear protein, anti-single-stranded DNA, anti-double-stranded DNA and anti-histone antibodies were measured in B10.A and B10.A recombinant mice neonatally infected with MuLV-Scripps (Lerner et al., 1972). The incidence and latency of lymphoma and the incidence of glomerulonephritis were also determined. The mice studied could be divided into high-responder and low-responder groups. Most of the high ANA antibody could be attributed to anti-histone antibody. High response was associated with the H-2b haplotype and recombinant strains on the B10 background which were identical at the I-A subregion derived from the H-2b parental stock. In contrast, low ANA response was associated with the I-A subregion derived from the H-2k haplotype. In all groups of virus-inoculated animals, most animals developed serum elevations of p30 and gp70 and at least 72% of the inoculated animals developed lymphomas. High serum p30 levels correlated inversely with latency and directly with gp70 values. From 4 to 28% of the animals in each virus-inoculated group had histological evidence of glomerulonephritis, although no clear genetic basis could be ascribed to the incidence of glomerulonephritis, serum p30 or gp70 levels, or latency of lymphoma development.", "contents": "Immunopathogenicity and oncogenicity of murine leukaemia virus. IV. Antinuclear antibody response and tumour induction in B10.A recombinant mice. The levels of murine leukaemia virus (MuLV) proteins p30 and gp70, antinuclear antibody (ANA), anti-soluble nuclear protein, anti-single-stranded DNA, anti-double-stranded DNA and anti-histone antibodies were measured in B10.A and B10.A recombinant mice neonatally infected with MuLV-Scripps (Lerner et al., 1972). The incidence and latency of lymphoma and the incidence of glomerulonephritis were also determined. The mice studied could be divided into high-responder and low-responder groups. Most of the high ANA antibody could be attributed to anti-histone antibody. High response was associated with the H-2b haplotype and recombinant strains on the B10 background which were identical at the I-A subregion derived from the H-2b parental stock. In contrast, low ANA response was associated with the I-A subregion derived from the H-2k haplotype. In all groups of virus-inoculated animals, most animals developed serum elevations of p30 and gp70 and at least 72% of the inoculated animals developed lymphomas. High serum p30 levels correlated inversely with latency and directly with gp70 values. From 4 to 28% of the animals in each virus-inoculated group had histological evidence of glomerulonephritis, although no clear genetic basis could be ascribed to the incidence of glomerulonephritis, serum p30 or gp70 levels, or latency of lymphoma development."}
{"id": "PMID:215681", "title": "Evidence that endotoxin is the cyclic 3':5'-GMP--promoting factor in erythropoietin preparations.", "content": "Since Ep preparations are contaminated with endotoxin, the possibility that the latter might be the factor in crude Ep which increases cGMP levels in rat fetal liver cells was examined. Endotoxin produced a striking elevation of cGMP in rat fetal liver cells without affecting cAMP levels or heme synthesis. Absorption with Limulus lysate of more than 99% of the endotoxin in a crude Ep preparation caused a parallel decrease in the cGMP-promoting activity without reduction of heme synthetic potency. It is concluded that endotoxin is the component of crude Ep which increases cGMP levels in rat fetal liver. The precise role of elevated cGMP in the action of endotoxin on cells and the universality of this effect remain to be determined.", "contents": "Evidence that endotoxin is the cyclic 3':5'-GMP--promoting factor in erythropoietin preparations. Since Ep preparations are contaminated with endotoxin, the possibility that the latter might be the factor in crude Ep which increases cGMP levels in rat fetal liver cells was examined. Endotoxin produced a striking elevation of cGMP in rat fetal liver cells without affecting cAMP levels or heme synthesis. Absorption with Limulus lysate of more than 99% of the endotoxin in a crude Ep preparation caused a parallel decrease in the cGMP-promoting activity without reduction of heme synthetic potency. It is concluded that endotoxin is the component of crude Ep which increases cGMP levels in rat fetal liver. The precise role of elevated cGMP in the action of endotoxin on cells and the universality of this effect remain to be determined."}
{"id": "PMID:215684", "title": "Origin and transport of the A-I and arginine-rich apolipoproteins in mesenteric lymph of rats.", "content": "Transport of apolipoprotein A-I and argininerich apolipoprotein in mesenteric lymph was examined in rats given constant intraduodenal infusions of saline, glucose in saline, or emulsified fat. Lymph flow in all groups was constant from 5 to 50 hr after beginning the infusions. Lymphatic transport of triglycerides was about 20-fold greater and transport of apoprotein A-I was about twofold greater in fat-infused rats than in the other two groups. In each group transport of apoprotein A-I bore a significant positive relationship to transport of triglycerides. Lymphatic transport of the arginine-rich apoprotein was only 6-12% of that of apoprotein A-I and was more closely related to lymphatic transport of total protein than to that of triglycerides. In fat-infused rats given [(3)H]lysine intraduodenally, about two-thirds of the (3)H in the chylomicron proteins was in apoprotein A-I and only about 1% was in the arginine-rich apoprotein. Estimated specific activity of chylomicron proteins was highest for apoprotein A-I and apoprotein A-IV, and lowest for the arginine-rich apoprotein and proteins of low molecular weight (mainly C apoproteins). In fat-infused rats given constant intravenous infusions of radioiodinated high density lipoproteins from blood plasma, the specific activity of apoprotein A-I in lymph chylomicrons was only about 5% of that of apoprotein A-I in blood high density lipoproteins, indicating that more than 90% of the apoprotein A-I in chylomicrons was synthesized in the intestine. From these and other data it is concluded that both the intestine and liver are significant sources of apoprotein A-I whereas only the liver synthesizes significant amounts of the arginine-rich apoprotein.", "contents": "Origin and transport of the A-I and arginine-rich apolipoproteins in mesenteric lymph of rats. Transport of apolipoprotein A-I and argininerich apolipoprotein in mesenteric lymph was examined in rats given constant intraduodenal infusions of saline, glucose in saline, or emulsified fat. Lymph flow in all groups was constant from 5 to 50 hr after beginning the infusions. Lymphatic transport of triglycerides was about 20-fold greater and transport of apoprotein A-I was about twofold greater in fat-infused rats than in the other two groups. In each group transport of apoprotein A-I bore a significant positive relationship to transport of triglycerides. Lymphatic transport of the arginine-rich apoprotein was only 6-12% of that of apoprotein A-I and was more closely related to lymphatic transport of total protein than to that of triglycerides. In fat-infused rats given [(3)H]lysine intraduodenally, about two-thirds of the (3)H in the chylomicron proteins was in apoprotein A-I and only about 1% was in the arginine-rich apoprotein. Estimated specific activity of chylomicron proteins was highest for apoprotein A-I and apoprotein A-IV, and lowest for the arginine-rich apoprotein and proteins of low molecular weight (mainly C apoproteins). In fat-infused rats given constant intravenous infusions of radioiodinated high density lipoproteins from blood plasma, the specific activity of apoprotein A-I in lymph chylomicrons was only about 5% of that of apoprotein A-I in blood high density lipoproteins, indicating that more than 90% of the apoprotein A-I in chylomicrons was synthesized in the intestine. From these and other data it is concluded that both the intestine and liver are significant sources of apoprotein A-I whereas only the liver synthesizes significant amounts of the arginine-rich apoprotein."}
{"id": "PMID:215685", "title": "Purification of polyphosphoinositides by chromatography on immobilized neomycin.", "content": "The binding of polyphosphoinositides (phosphatidylinositol phosphate and phosphatidylinositol bisphosphate) to the antibiotic neomycin is utilized for the purification of these lipids. Neomycin is reductively coupled to reactive glass beads (Glycophase-CPG) and serves as the stationary phase in column chromatography. A total lipid extract is prepared from tissues with chloroform-methanol-KC1 or chloroform-methanol-HC1 and washed once with acidified methanol-water. After the addition of an equal volume of methanolic 200 mM ammonium acetate, the extract is directly applied to the column. All lipids but the polyphosphoinositides are removed from the column by rinsing with 150 mM ammonium acetate in chloroform-methanol-water. Increasing the salt concentration to 600 mM elutes phosphatidylinositol phosphate. While further increases in ionic strength are not sufficient for a quantitative removal of phosphatidylinositol bisphosphate, the lipid is completely eluted by the addition of either ammonia or HC1 to the solvent. The column can be recycled and used repeatedly.", "contents": "Purification of polyphosphoinositides by chromatography on immobilized neomycin. The binding of polyphosphoinositides (phosphatidylinositol phosphate and phosphatidylinositol bisphosphate) to the antibiotic neomycin is utilized for the purification of these lipids. Neomycin is reductively coupled to reactive glass beads (Glycophase-CPG) and serves as the stationary phase in column chromatography. A total lipid extract is prepared from tissues with chloroform-methanol-KC1 or chloroform-methanol-HC1 and washed once with acidified methanol-water. After the addition of an equal volume of methanolic 200 mM ammonium acetate, the extract is directly applied to the column. All lipids but the polyphosphoinositides are removed from the column by rinsing with 150 mM ammonium acetate in chloroform-methanol-water. Increasing the salt concentration to 600 mM elutes phosphatidylinositol phosphate. While further increases in ionic strength are not sufficient for a quantitative removal of phosphatidylinositol bisphosphate, the lipid is completely eluted by the addition of either ammonia or HC1 to the solvent. The column can be recycled and used repeatedly."}
{"id": "PMID:215686", "title": "Endogenously labeled low density lipoprotein triglyceride and apoprotein B kinetics.", "content": "The kinetics of endogenously labeled low density lipoprotein (LDL) triglycerides (TG) and apoprotein B (apoB) have been studied in four normal and in four hyperlipemic subjects using double tracers. Analysis of the data suggests that most LDL triglycerides turn over about 10 times faster than apoB (0.003/min vs. 0.0003/min) and that about 10% of the LDL particles contain most of the TG found with LDL. It is not possible to determine from the analysis whether each new LDL particle arrives with the excess TG or whether only a subpopulation of particles contains most of the TG. The kinetic analysis further suggests that triglyceride-rich LDL particles do not exchange with an extraplasma compartment as most LDL particles do, and thus, they behave more like very low density lipoprotein particles. A compartmental model accounting for both the LDL-TG and LDL-apoB kinetics is proposed.", "contents": "Endogenously labeled low density lipoprotein triglyceride and apoprotein B kinetics. The kinetics of endogenously labeled low density lipoprotein (LDL) triglycerides (TG) and apoprotein B (apoB) have been studied in four normal and in four hyperlipemic subjects using double tracers. Analysis of the data suggests that most LDL triglycerides turn over about 10 times faster than apoB (0.003/min vs. 0.0003/min) and that about 10% of the LDL particles contain most of the TG found with LDL. It is not possible to determine from the analysis whether each new LDL particle arrives with the excess TG or whether only a subpopulation of particles contains most of the TG. The kinetic analysis further suggests that triglyceride-rich LDL particles do not exchange with an extraplasma compartment as most LDL particles do, and thus, they behave more like very low density lipoprotein particles. A compartmental model accounting for both the LDL-TG and LDL-apoB kinetics is proposed."}
{"id": "PMID:215687", "title": "Male--female variability in the dietary cholesterol-induced hyperlipoproteinemia of cynomolgus monkeys (Macaca fascicularis).", "content": "The characteristics of dietary cholesterol-induced hyperlipoproteinemia were studied in adult Macaca fascicularis to determine if significant male--female differences could be identified. The plasma lipoproteins from individual animals were separated by agarose column chromatography and the resulting size populations of lipoproteins were chemically characterized. The distribution of constituents among the lipoprotein classes was determined. The lipoproteins that increased most significantly in response to dietary cholesterol were the low density lipoproteins (LDL) which were those of region III of the column elution profile. The LDL mass concentrations (in mg/dl of plasma) were not different between males and females. However, these lipoproteins showed a characteristic difference between males and females in response to dietary cholesterol. The primary response in the males was an increased LDL molecular weight. In females, the primary response was an increased number of LDL particles (measured as mumolar concentration). Thus, at the same LDL mass concentration, males had significantly larger LDL particles and yet fewer of them. Analysis of the chemical composition data showed that size differences between LDL of males and females was due primarily to the incorporation of more cholesteryl ester into the LDL particles from male animals; the content per LDL particle of free cholesterol, phospholipid, and protein showed the same proportionality to size for both sexes. Another significant difference between lipoproteins of males and females was in the extent to which the plasma HDL (identified in these studies as the lipoproteins of region IV of the elution profile) decreased in response to dietary cholesterol. Chemical composition differences were also noted. The HDL particles of males and of cholesterol-fed animals contained more cholesteryl ester than did HDL of females and control animals, respectively.", "contents": "Male--female variability in the dietary cholesterol-induced hyperlipoproteinemia of cynomolgus monkeys (Macaca fascicularis). The characteristics of dietary cholesterol-induced hyperlipoproteinemia were studied in adult Macaca fascicularis to determine if significant male--female differences could be identified. The plasma lipoproteins from individual animals were separated by agarose column chromatography and the resulting size populations of lipoproteins were chemically characterized. The distribution of constituents among the lipoprotein classes was determined. The lipoproteins that increased most significantly in response to dietary cholesterol were the low density lipoproteins (LDL) which were those of region III of the column elution profile. The LDL mass concentrations (in mg/dl of plasma) were not different between males and females. However, these lipoproteins showed a characteristic difference between males and females in response to dietary cholesterol. The primary response in the males was an increased LDL molecular weight. In females, the primary response was an increased number of LDL particles (measured as mumolar concentration). Thus, at the same LDL mass concentration, males had significantly larger LDL particles and yet fewer of them. Analysis of the chemical composition data showed that size differences between LDL of males and females was due primarily to the incorporation of more cholesteryl ester into the LDL particles from male animals; the content per LDL particle of free cholesterol, phospholipid, and protein showed the same proportionality to size for both sexes. Another significant difference between lipoproteins of males and females was in the extent to which the plasma HDL (identified in these studies as the lipoproteins of region IV of the elution profile) decreased in response to dietary cholesterol. Chemical composition differences were also noted. The HDL particles of males and of cholesterol-fed animals contained more cholesteryl ester than did HDL of females and control animals, respectively."}
{"id": "PMID:215688", "title": "Bronchogenic carcinoma metastasizing to the orbit. A case report.", "content": "A case of an orbital metastasis from a bronchogenic neoplasm is described. The initial clinical presentation was of unilateral facial pain and paraesthesia shortly followed by increasing left-sided external ophthalmoplegia and proptosis and the development of a slight swelling of the left temporal fossa. The diagnosis was established by a biopsy of the temporal mass. The patient died two months after the diagnosis was established. The significance of facial pain and paraesthesia and the literature pertaining to orbital cellulitis and orbital metastases is discussed.", "contents": "Bronchogenic carcinoma metastasizing to the orbit. A case report. A case of an orbital metastasis from a bronchogenic neoplasm is described. The initial clinical presentation was of unilateral facial pain and paraesthesia shortly followed by increasing left-sided external ophthalmoplegia and proptosis and the development of a slight swelling of the left temporal fossa. The diagnosis was established by a biopsy of the temporal mass. The patient died two months after the diagnosis was established. The significance of facial pain and paraesthesia and the literature pertaining to orbital cellulitis and orbital metastases is discussed."}
{"id": "PMID:215689", "title": "Diurnal variations in the influence of the ultimobranchial glands on calcium homeostasis in the frog (Rana pipiens).", "content": "The effect of the light-darkness cycle on the efficiency of the ultimobranchial and parathyroid glands in altering duodenal calcium transport and plasma and urinary concentrations of calcium was examined in the adult male frog (Rana pipiens). Frogs were unfed, but were allowed access to 0.05 M-CaCl2 in the surrounding medium after ultimobranchialectomy or parathyroidectomy. Calcium transport, as assayed by the everted gut-sac technique, was increased in ultimobranchialectomized frogs at sunrise, concomitant with acute hypercalcaemia and hypercalciuria. An opposite but chronic response was observed in parathyroidectomized frogs with intact ultimobranchial glands. The maximum response observed at sunrise occurred when the concentration of calcium in the plasma of control frogs was decreasing; the minimum response, which occurred 6 h after sunrise, was coincident with a diurnal peak in the concentration of calcium. Vitamin D3 (500 microgram/frog) enhanced calcium transport in ultimobranchialectomized frogs, which resulted in chronic hypercalcaemia and hypercalciuria. The results suggest that diurnal variations in the plasma concentration of calcium do not initiate ultimobranchial activity, but are a response to endocrine control synchronized with the transition from darkness to light.", "contents": "Diurnal variations in the influence of the ultimobranchial glands on calcium homeostasis in the frog (Rana pipiens). The effect of the light-darkness cycle on the efficiency of the ultimobranchial and parathyroid glands in altering duodenal calcium transport and plasma and urinary concentrations of calcium was examined in the adult male frog (Rana pipiens). Frogs were unfed, but were allowed access to 0.05 M-CaCl2 in the surrounding medium after ultimobranchialectomy or parathyroidectomy. Calcium transport, as assayed by the everted gut-sac technique, was increased in ultimobranchialectomized frogs at sunrise, concomitant with acute hypercalcaemia and hypercalciuria. An opposite but chronic response was observed in parathyroidectomized frogs with intact ultimobranchial glands. The maximum response observed at sunrise occurred when the concentration of calcium in the plasma of control frogs was decreasing; the minimum response, which occurred 6 h after sunrise, was coincident with a diurnal peak in the concentration of calcium. Vitamin D3 (500 microgram/frog) enhanced calcium transport in ultimobranchialectomized frogs, which resulted in chronic hypercalcaemia and hypercalciuria. The results suggest that diurnal variations in the plasma concentration of calcium do not initiate ultimobranchial activity, but are a response to endocrine control synchronized with the transition from darkness to light."}
{"id": "PMID:215690", "title": "Hypothalamic corticotrophin releasing factor activity in dogs with pituitary-dependent hyperadrenocorticism.", "content": "Hypothalamic corticotrophin releasing factor (CRF) activity was determined in five dogs with spontaneous hyperadrenocorticism and in three control animals (one untreated, one treated with high doses of ACTH for 2 months and one treated with high doses of cortisone for 2 months). Hypothalamic CRF activity was low or undetectable in four dogs with Cushing's syndrome due to an adrenocortical tumour. The results are compatible with a pituitary origin for pituitary-dependent hyperadrenocorticism in the dog but are not conclusive; direct information about the rates of hypothalamic CRF secretion is required.", "contents": "Hypothalamic corticotrophin releasing factor activity in dogs with pituitary-dependent hyperadrenocorticism. Hypothalamic corticotrophin releasing factor (CRF) activity was determined in five dogs with spontaneous hyperadrenocorticism and in three control animals (one untreated, one treated with high doses of ACTH for 2 months and one treated with high doses of cortisone for 2 months). Hypothalamic CRF activity was low or undetectable in four dogs with Cushing's syndrome due to an adrenocortical tumour. The results are compatible with a pituitary origin for pituitary-dependent hyperadrenocorticism in the dog but are not conclusive; direct information about the rates of hypothalamic CRF secretion is required."}
{"id": "PMID:215701", "title": "The regulation of the calcium sensitivity of the contractile system in mammalian cardiac muscle.", "content": "Treatment of rat ventricular cells with 10 mM EGTA makes the sarcolemma highly permeable to small ions and molecules without removing its restriction of the diffusion of larger molecules or inactivating all of its enzymatic functions. These hyperpermeable cardiac cells have been used to study the regulation of the range of concentration of Ca over which activation of the contractile proteins occurs (Ca sensitivity). The Ca sensitivity can varied from three- to sixfold without any significant alteration in the general shape of the relation between force and Ca concentrations. Although cyclic nucleotides in concentrations of 10(-9) to 10(-5) M do not influence Ca sensitivity, in the presence of a phosphodiesterase inhibitor, cGMP increases and cAMP decreases Ca sensitivity. Treatment of the hyperpermeable cells with a nonionic detergent raises Ca sensitivity as does removal of the phosphate donor by complete substitution of CTP for ATP. These data indicate that Ca sensitivity is probably modulated by a cAMP-dependent phosphorylation that decreases Ca sensitivity. The sarcolemma is required for this reaction to take place. The effect of this reaction is antagonized by a cGMP-dependent reaction occurring inside the cell. Studies involving the perfusion of the heart with and without epinephrine before the exposure to EGTA indicate that epinephrine can regulate this system of control of Ca sensitivity. The functional considerations of this regulatory system are discussed.", "contents": "The regulation of the calcium sensitivity of the contractile system in mammalian cardiac muscle. Treatment of rat ventricular cells with 10 mM EGTA makes the sarcolemma highly permeable to small ions and molecules without removing its restriction of the diffusion of larger molecules or inactivating all of its enzymatic functions. These hyperpermeable cardiac cells have been used to study the regulation of the range of concentration of Ca over which activation of the contractile proteins occurs (Ca sensitivity). The Ca sensitivity can varied from three- to sixfold without any significant alteration in the general shape of the relation between force and Ca concentrations. Although cyclic nucleotides in concentrations of 10(-9) to 10(-5) M do not influence Ca sensitivity, in the presence of a phosphodiesterase inhibitor, cGMP increases and cAMP decreases Ca sensitivity. Treatment of the hyperpermeable cells with a nonionic detergent raises Ca sensitivity as does removal of the phosphate donor by complete substitution of CTP for ATP. These data indicate that Ca sensitivity is probably modulated by a cAMP-dependent phosphorylation that decreases Ca sensitivity. The sarcolemma is required for this reaction to take place. The effect of this reaction is antagonized by a cGMP-dependent reaction occurring inside the cell. Studies involving the perfusion of the heart with and without epinephrine before the exposure to EGTA indicate that epinephrine can regulate this system of control of Ca sensitivity. The functional considerations of this regulatory system are discussed."}
{"id": "PMID:215702", "title": "The effect of pneumonia induced in mice with Mycoplasma pulmonis on resistance to subsequent bacterial infection and the effect of a respiratory infection with Sendai virus on the resistance of mice to Mycoplasma pulmonis.", "content": "The effect of pneumonia induced by Mycoplasma pulmonis in mice on the resistance of the lung to additional bacterial infection was examined. The effect of pneumonia induced by Sendai virus on the resistance of mice to M. pulmonis was also investigated and compared with the effect of Sendai virus on resistance to Staphylococcus aureus. Sendai virus infection decreased subsequent resistance to M. pulmonis in proportion to the virus dose. Decreased resistance to subsequent S. aureus and M. pulmonis infection was greatest at about the same time after inoculation of virus and was related to virus-induced lesions. Besides affecting the resistance of mice to subsequent mycoplasma infection, Sendai virus could enhance an existing mycoplasma infection. Pneumonia induced by M. pulmonis did not decrease resistance to subsequent bacterial infection. The mechanism whereby Sendai virus decreases host resistance is therefore similar for bacteria and mycoplasmas, but pneumonia induced by mycoplasmas does not have the same effect.", "contents": "The effect of pneumonia induced in mice with Mycoplasma pulmonis on resistance to subsequent bacterial infection and the effect of a respiratory infection with Sendai virus on the resistance of mice to Mycoplasma pulmonis. The effect of pneumonia induced by Mycoplasma pulmonis in mice on the resistance of the lung to additional bacterial infection was examined. The effect of pneumonia induced by Sendai virus on the resistance of mice to M. pulmonis was also investigated and compared with the effect of Sendai virus on resistance to Staphylococcus aureus. Sendai virus infection decreased subsequent resistance to M. pulmonis in proportion to the virus dose. Decreased resistance to subsequent S. aureus and M. pulmonis infection was greatest at about the same time after inoculation of virus and was related to virus-induced lesions. Besides affecting the resistance of mice to subsequent mycoplasma infection, Sendai virus could enhance an existing mycoplasma infection. Pneumonia induced by M. pulmonis did not decrease resistance to subsequent bacterial infection. The mechanism whereby Sendai virus decreases host resistance is therefore similar for bacteria and mycoplasmas, but pneumonia induced by mycoplasmas does not have the same effect."}
{"id": "PMID:215704", "title": "Ultrastructural development of guinea pig cytomegalovirus in cultured guinea pig embryo cells.", "content": "The ultrastructural development of guinea pig cytomegalovirus (GPCMV) in guinea pig embryo cells was studied using electron microscopy. Tubular structures were found in nuclei of virus infected cells, followed by the appearance of intranuclear inclusions containing virus nucleocapsids. While some nucleocapsids were enveloped at the inner nuclear membrane, others were released into the cytoplasm where they were associated with, or within, dense matrix which was subsequently enveloped by cytoplasmic membranes to form enveloped dense virions. Dense bodies without virus capsids were formed in the cytoplasm and enveloped in a similar manner. An involvement of the nuclear pores in the release of unenveloped virus capsids from the nucleus to the cytoplasm was postulated. Evidence that the enveloped dense virions and dense bodies shared common envelope antigen(s) was obtained by immunoelectron microscopy. The similarities and differences in the ultrastructural development of GPCMV and other cytomegaloviruses are discussed.", "contents": "Ultrastructural development of guinea pig cytomegalovirus in cultured guinea pig embryo cells. The ultrastructural development of guinea pig cytomegalovirus (GPCMV) in guinea pig embryo cells was studied using electron microscopy. Tubular structures were found in nuclei of virus infected cells, followed by the appearance of intranuclear inclusions containing virus nucleocapsids. While some nucleocapsids were enveloped at the inner nuclear membrane, others were released into the cytoplasm where they were associated with, or within, dense matrix which was subsequently enveloped by cytoplasmic membranes to form enveloped dense virions. Dense bodies without virus capsids were formed in the cytoplasm and enveloped in a similar manner. An involvement of the nuclear pores in the release of unenveloped virus capsids from the nucleus to the cytoplasm was postulated. Evidence that the enveloped dense virions and dense bodies shared common envelope antigen(s) was obtained by immunoelectron microscopy. The similarities and differences in the ultrastructural development of GPCMV and other cytomegaloviruses are discussed."}
{"id": "PMID:215705", "title": "Pseudotypes of vesicular stomatitis virus and Pichinde virus.", "content": "Super-infection of Pichinde virus-infected cells with vesicular stomatitis virus (VSV) resulted in the production of pseudotype virus which was not neutralized by antiserum to VSV but which was neutralized by antiserum to Pichinde virus. Analysis of pseudotype virus production in relation to the kinetics of replication of Pichinde virus demonstrated that pseudotype virus production occurred when super-infection with VSV was initiated 8 h or more after infecting the cells with Pichinde virus. The quantities of pseudotype virus produced correlated with the quantities of Pichinde virus antigen detected on the surface of the cells both during acute infection and in cells chronically infected with Pichinde virus. The observations indicate that pseudotype of VSV and Pichinde virus are readily formed and that the formation of pseudotype virus may be used to examine the Pichinde virus antigens expressed on the surface of infected cells.", "contents": "Pseudotypes of vesicular stomatitis virus and Pichinde virus. Super-infection of Pichinde virus-infected cells with vesicular stomatitis virus (VSV) resulted in the production of pseudotype virus which was not neutralized by antiserum to VSV but which was neutralized by antiserum to Pichinde virus. Analysis of pseudotype virus production in relation to the kinetics of replication of Pichinde virus demonstrated that pseudotype virus production occurred when super-infection with VSV was initiated 8 h or more after infecting the cells with Pichinde virus. The quantities of pseudotype virus produced correlated with the quantities of Pichinde virus antigen detected on the surface of the cells both during acute infection and in cells chronically infected with Pichinde virus. The observations indicate that pseudotype of VSV and Pichinde virus are readily formed and that the formation of pseudotype virus may be used to examine the Pichinde virus antigens expressed on the surface of infected cells."}
{"id": "PMID:215706", "title": "Characterization of human TK- cell lines transformed to a TK+ phenotype by herpes simplex virus type 2 DNA.", "content": "Human TK- cells carrying the HSV-2 TK gene as a result of transformation with virus DNA express a TK activity of virus origin and maintain the TK+ phenotype when grown in HAT medium. Under non-selective conditions, however, reversion to a TK- phenotype occurs with a significant frequency characteristic of each transformed line. Once reversion has occurred the TK- phenotype appears to be stable, since only very rare instances of TK- to TK+ reversion have been observed. TK- revertants were susceptible to re-transformation by virus DNA, but no reactivation of a silent virus TK gene could be obtained by superinfecting them with a TK- virus mutant. The data presented are consistent with the hypothesis that acquisition of the TK- phenotype is brought about by loss of the virus sequences coding for TK.", "contents": "Characterization of human TK- cell lines transformed to a TK+ phenotype by herpes simplex virus type 2 DNA. Human TK- cells carrying the HSV-2 TK gene as a result of transformation with virus DNA express a TK activity of virus origin and maintain the TK+ phenotype when grown in HAT medium. Under non-selective conditions, however, reversion to a TK- phenotype occurs with a significant frequency characteristic of each transformed line. Once reversion has occurred the TK- phenotype appears to be stable, since only very rare instances of TK- to TK+ reversion have been observed. TK- revertants were susceptible to re-transformation by virus DNA, but no reactivation of a silent virus TK gene could be obtained by superinfecting them with a TK- virus mutant. The data presented are consistent with the hypothesis that acquisition of the TK- phenotype is brought about by loss of the virus sequences coding for TK."}
{"id": "PMID:215707", "title": "Murine cytomegalovirus-induced protein synthesis.", "content": "Murine cytomegalovirus (MCMV)-induced protein synthesis in mouse embryo fibroblast (MEF) cells was studied using polyacrylamide gradient SDS gel electrophoresis and autoradiography. Synthesis of at least 14 virus induced proteins (VIPs) was consistently detected in a lytic cycle. They were designated VIPs 132, 118, 99, 98, 88, 81, 76, 74, 58, 56, 51, 38, 36 and 33 on the basis of their mol. wt. Judging from the pattern of the rate of protein synthesis, VIPs can be classified into three groups: group A VIPs were synthesized actively for a brief period of time and then their synthesis was no longer detectable. This group included two major VIPs, 98 and 88 and three minor VIPs, 58, 56 and 38. Group B VIPs 81, 74, 36 and 33 were similar to group A except that, following a brief period of active synthesis, a low level of synthesis continued during the entire lytic cycle. Group C VIPs 132, 118, 99, 76 and 51 were synthesized at low steady levels at all times after initiation and seemed to accumulate slowly. According to temporal sequences of initiation of VIP synthesis, these proteins can also be divided into three groups: immediate early, early and late VIPs. The synthesis of the immediate early VIPs 132, 98, 88, 81, 76, 74 and 38 was initiated immediately after virus infection. The early VIPs included 58, 56, 51, 36 and 33 and their synthesis was initiated from 1 to 3 h post-infection. VIPs 118, 99 and several minor VIPs were first synthesized during 12 to 13 h post-infection which corresponded to the time of initiation of virus DNA synthesis and they are classified as late VIPs. Cycloheximide reversal experiments indicated that the initiation of synthesis of early VIPs must be preceded by the synthesis of immediate early VIPs. In the presence of actinomycin D, the immediate early VIPs (0 to 1 h post-infection) were not synthesized indicating that immediate early VIPs are translated from virus mRNA synthesized after virus infection.", "contents": "Murine cytomegalovirus-induced protein synthesis. Murine cytomegalovirus (MCMV)-induced protein synthesis in mouse embryo fibroblast (MEF) cells was studied using polyacrylamide gradient SDS gel electrophoresis and autoradiography. Synthesis of at least 14 virus induced proteins (VIPs) was consistently detected in a lytic cycle. They were designated VIPs 132, 118, 99, 98, 88, 81, 76, 74, 58, 56, 51, 38, 36 and 33 on the basis of their mol. wt. Judging from the pattern of the rate of protein synthesis, VIPs can be classified into three groups: group A VIPs were synthesized actively for a brief period of time and then their synthesis was no longer detectable. This group included two major VIPs, 98 and 88 and three minor VIPs, 58, 56 and 38. Group B VIPs 81, 74, 36 and 33 were similar to group A except that, following a brief period of active synthesis, a low level of synthesis continued during the entire lytic cycle. Group C VIPs 132, 118, 99, 76 and 51 were synthesized at low steady levels at all times after initiation and seemed to accumulate slowly. According to temporal sequences of initiation of VIP synthesis, these proteins can also be divided into three groups: immediate early, early and late VIPs. The synthesis of the immediate early VIPs 132, 98, 88, 81, 76, 74 and 38 was initiated immediately after virus infection. The early VIPs included 58, 56, 51, 36 and 33 and their synthesis was initiated from 1 to 3 h post-infection. VIPs 118, 99 and several minor VIPs were first synthesized during 12 to 13 h post-infection which corresponded to the time of initiation of virus DNA synthesis and they are classified as late VIPs. Cycloheximide reversal experiments indicated that the initiation of synthesis of early VIPs must be preceded by the synthesis of immediate early VIPs. In the presence of actinomycin D, the immediate early VIPs (0 to 1 h post-infection) were not synthesized indicating that immediate early VIPs are translated from virus mRNA synthesized after virus infection."}
{"id": "PMID:215708", "title": "Varicella-zoster virus immunizes patas monkeys against simian varicella-like disease.", "content": "To define further the antigenic relationship between human varicella-zoster virus and herpesviruses which produce varicella-like disease in certain simian species, patas monkeys were inoculated with varicella-zoster virus and then challenged with Delta herpesvirus, which uniformly produces severe, clinically apparent disease in susceptible animals. Protection against Delta herpesvirus was conferred both by hyperimmunization with varicella-zoster virus and by a single immunization with a cell-free preparation of varicella-zoster virus. Although the immunological relationship between the human and simian varicella viruses is not completely reciprocal, these studies confirmed that antigens which induce immunity are shared by the human and simian viruses. No clinical symptoms were seen in monkeys inoculated with varicella-zoster virus, but the rapid and marked antibody responses to the virus suggested that subclinical infection had occurred. In contrast, a chimpanzee inoculated with one of the same varicella-zoster virus preparations produced only low levels of antibody.", "contents": "Varicella-zoster virus immunizes patas monkeys against simian varicella-like disease. To define further the antigenic relationship between human varicella-zoster virus and herpesviruses which produce varicella-like disease in certain simian species, patas monkeys were inoculated with varicella-zoster virus and then challenged with Delta herpesvirus, which uniformly produces severe, clinically apparent disease in susceptible animals. Protection against Delta herpesvirus was conferred both by hyperimmunization with varicella-zoster virus and by a single immunization with a cell-free preparation of varicella-zoster virus. Although the immunological relationship between the human and simian varicella viruses is not completely reciprocal, these studies confirmed that antigens which induce immunity are shared by the human and simian viruses. No clinical symptoms were seen in monkeys inoculated with varicella-zoster virus, but the rapid and marked antibody responses to the virus suggested that subclinical infection had occurred. In contrast, a chimpanzee inoculated with one of the same varicella-zoster virus preparations produced only low levels of antibody."}
{"id": "PMID:215709", "title": "Concentration of human cytomegalovirus from large volumes of tissue culture fluids.", "content": "Three methods of pelleting, ultracentrifugation (95000 g for 60 min), precipitation with polyethylene glycol 6000 (5% v/v), and with ammonium sulphate (38% w/v), were used to concentrate human cytomegalovirus (CMV) from tissue culture fluids. Maximum recovery of infectious virus particles was obtained with the polyethylene glycol (PEG) method. The precipitating activity of PEG 6000 and PEG 20000 was then compared at different concentrations. The best results were obtained with PEG 6000 at a final concentration of 5% (v/v). Changes in pH or salt concentration, treatment of the concentrates with Pronase and long periods of time at 4 degrees C significantly reduced the number of biologically active CMV particles recovered by PEG precipitation.", "contents": "Concentration of human cytomegalovirus from large volumes of tissue culture fluids. Three methods of pelleting, ultracentrifugation (95000 g for 60 min), precipitation with polyethylene glycol 6000 (5% v/v), and with ammonium sulphate (38% w/v), were used to concentrate human cytomegalovirus (CMV) from tissue culture fluids. Maximum recovery of infectious virus particles was obtained with the polyethylene glycol (PEG) method. The precipitating activity of PEG 6000 and PEG 20000 was then compared at different concentrations. The best results were obtained with PEG 6000 at a final concentration of 5% (v/v). Changes in pH or salt concentration, treatment of the concentrates with Pronase and long periods of time at 4 degrees C significantly reduced the number of biologically active CMV particles recovered by PEG precipitation."}
{"id": "PMID:215710", "title": "The kinetics of synthesis of infectious unintegrated virus DNA in rous sarcoma virus infected chicken cells.", "content": "Infectious virus nucleic acids were extracted from the Hirt supernatant of chicken embryo fibroblasts infected for different times with the Schmidt-Ruppin strain of Rous sarcoma virus (RSV). Infectious DNA and DNA-RNA hybrid molecules could be recovered from 6 h after infection in experiments using 1.5 X 10(9) infected cells. Only small amounts of infectious virus DNA could be purified 6 h after infection whereas at 24 h approximately one infectious DNA molecule could be recovered for each input virus infectious unit. At 24 h, both infectious supercoiled and non-supercoiled molecules were found. The specific infectivity of the supercoiled fraction was less than that of the non-supercoiled fraction. Infectious supercoiled DNA could be recovered from 16 h after infection. Evidence is presented that both forms of unintegrated virus DNA may rest unintegrated for at least 8 days in the cell, though chronically infected cells were shown to contain less than one unintegrated molecule per 10(2) to 10(3) cells.", "contents": "The kinetics of synthesis of infectious unintegrated virus DNA in rous sarcoma virus infected chicken cells. Infectious virus nucleic acids were extracted from the Hirt supernatant of chicken embryo fibroblasts infected for different times with the Schmidt-Ruppin strain of Rous sarcoma virus (RSV). Infectious DNA and DNA-RNA hybrid molecules could be recovered from 6 h after infection in experiments using 1.5 X 10(9) infected cells. Only small amounts of infectious virus DNA could be purified 6 h after infection whereas at 24 h approximately one infectious DNA molecule could be recovered for each input virus infectious unit. At 24 h, both infectious supercoiled and non-supercoiled molecules were found. The specific infectivity of the supercoiled fraction was less than that of the non-supercoiled fraction. Infectious supercoiled DNA could be recovered from 16 h after infection. Evidence is presented that both forms of unintegrated virus DNA may rest unintegrated for at least 8 days in the cell, though chronically infected cells were shown to contain less than one unintegrated molecule per 10(2) to 10(3) cells."}
{"id": "PMID:215711", "title": "Rapid purification of lymphocytic choriomeningitis virus by density gradient centrifugation in colloidal silica.", "content": "Lymphocytic choriomeningitis virus was purified from cell culture fluid by density gradient centrifugation in colloidal silica. The specific infectivity increased 5000-fold and the recovery of infectivity was about 10%.", "contents": "Rapid purification of lymphocytic choriomeningitis virus by density gradient centrifugation in colloidal silica. Lymphocytic choriomeningitis virus was purified from cell culture fluid by density gradient centrifugation in colloidal silica. The specific infectivity increased 5000-fold and the recovery of infectivity was about 10%."}
{"id": "PMID:215712", "title": "Detection of polyoma virus DNA in PML-brain tissue by (in situ) hybridization.", "content": "The human papova (JC) virus was extracted from brain of a patient with progressive multifocal leukoencephalopathy. A single band of virus was obtained at a density of 1.345 g/ml CsCl.JC virus DNA was purified and a highly specific cRNA was generated in vitro. In situ hybridization with JC virus cRNA and autoradiography on sections of the same brain revealed silver grains over oligodendrocytes, astrocytes and possible vascular endothelial cells, indicating the presence of JC virus DNA in these different cell classes.", "contents": "Detection of polyoma virus DNA in PML-brain tissue by (in situ) hybridization. The human papova (JC) virus was extracted from brain of a patient with progressive multifocal leukoencephalopathy. A single band of virus was obtained at a density of 1.345 g/ml CsCl.JC virus DNA was purified and a highly specific cRNA was generated in vitro. In situ hybridization with JC virus cRNA and autoradiography on sections of the same brain revealed silver grains over oligodendrocytes, astrocytes and possible vascular endothelial cells, indicating the presence of JC virus DNA in these different cell classes."}
{"id": "PMID:215713", "title": "Prevalence of antibody to the Norwalk agent by a newly developed immune adherence hemagglutination assay.", "content": "An immune adherence hemagglutination assay (IAHA) for the detection of antibody to the Norwalk agent of acute epidemic nonbacterial gastroenteritis was developed using as antigen virus purified from stool from an experimentally infected volunteer. The assay was sensitive and specific and was efficient for detecting Norwalk antibody seroresponses. The prevalence of Norwalk antibody in various groups in the United States was studied. Antibody to the Norwalk agent was acquired gradually, beginning slowly in childhood and accelerating in the adult period so that by the fifth decade 50% possessed antibody. This pattern of antibody acquisition contrasted sharply with that for the human rotavirus of infantile gastroenteritis. Rotavirus antibody was acquired during early childhood by almost all individuals in the pediatric groups studied. Antibody to the Norwalk agent was also found in rural Bangladesh; in a small prevalence survey of 39 children and adults 21% possessed Norwalk IAHA antibody, whereas 95% possessed antibody to the human rotavirus.", "contents": "Prevalence of antibody to the Norwalk agent by a newly developed immune adherence hemagglutination assay. An immune adherence hemagglutination assay (IAHA) for the detection of antibody to the Norwalk agent of acute epidemic nonbacterial gastroenteritis was developed using as antigen virus purified from stool from an experimentally infected volunteer. The assay was sensitive and specific and was efficient for detecting Norwalk antibody seroresponses. The prevalence of Norwalk antibody in various groups in the United States was studied. Antibody to the Norwalk agent was acquired gradually, beginning slowly in childhood and accelerating in the adult period so that by the fifth decade 50% possessed antibody. This pattern of antibody acquisition contrasted sharply with that for the human rotavirus of infantile gastroenteritis. Rotavirus antibody was acquired during early childhood by almost all individuals in the pediatric groups studied. Antibody to the Norwalk agent was also found in rural Bangladesh; in a small prevalence survey of 39 children and adults 21% possessed Norwalk IAHA antibody, whereas 95% possessed antibody to the human rotavirus."}
{"id": "PMID:215714", "title": "Prevalence of antibody to the hepatitis A virus in a large institution for the mentally retarded.", "content": "The prevalence of antibody to hepatitis A virus (anti-HAV) was determined in 854 people living in a large institution for the mentally retarded in Melbourne. Altogether 638 (74.4%) of the subjects were found to have specific antibody detectable by solid-phase radioimmunoassay (SPRIA). No difference in antibody prevalence was observed between males and females; however, the prevalence was higher among subjects with Down syndrome (84.1%) than those of other forms of mental retardation (72.8%). In both groups there was an increase in prevalence of antibody with increasing age and duration of institutionalization. When compared with the open community, patients in this institution have a higher prevalence of antibody and appear to acquire their infections at an earlier age.", "contents": "Prevalence of antibody to the hepatitis A virus in a large institution for the mentally retarded. The prevalence of antibody to hepatitis A virus (anti-HAV) was determined in 854 people living in a large institution for the mentally retarded in Melbourne. Altogether 638 (74.4%) of the subjects were found to have specific antibody detectable by solid-phase radioimmunoassay (SPRIA). No difference in antibody prevalence was observed between males and females; however, the prevalence was higher among subjects with Down syndrome (84.1%) than those of other forms of mental retardation (72.8%). In both groups there was an increase in prevalence of antibody with increasing age and duration of institutionalization. When compared with the open community, patients in this institution have a higher prevalence of antibody and appear to acquire their infections at an earlier age."}
{"id": "PMID:215715", "title": "Diagnosis of human coronavirus infection by immunofluorescence: method and application to respiratory disease in hospitalized children.", "content": "Rabbit antisera were prepared against coronavirus strains 229E and OC43 and used successfully to detect viral antigen in epithelial cells shed from the nasopharynx of symptomatic volunteers who had received coronavirus inocula three to four days before. The same serologic reagents were applied to nasopharyngeal secretion cells obtained from 106 infants and children hospitalized with respiratory tract disease and apparently not infected with conventional respiratory viruses. No coronavirus infections were detected by this method. It appears that coronavirus OC43 or 229E infections were not common in children in Tyneside hospitals during the period of study. However, fluorescence is a useful method for detection of coronavirus infections in symptomatic human subjects.", "contents": "Diagnosis of human coronavirus infection by immunofluorescence: method and application to respiratory disease in hospitalized children. Rabbit antisera were prepared against coronavirus strains 229E and OC43 and used successfully to detect viral antigen in epithelial cells shed from the nasopharynx of symptomatic volunteers who had received coronavirus inocula three to four days before. The same serologic reagents were applied to nasopharyngeal secretion cells obtained from 106 infants and children hospitalized with respiratory tract disease and apparently not infected with conventional respiratory viruses. No coronavirus infections were detected by this method. It appears that coronavirus OC43 or 229E infections were not common in children in Tyneside hospitals during the period of study. However, fluorescence is a useful method for detection of coronavirus infections in symptomatic human subjects."}
{"id": "PMID:215716", "title": "Infection of human amnion cells with cytomegalovirus.", "content": "Human cytomegalovirus (CMV), known to replicate in vitro in human fibroblastic cells, was found to replicate in epithelial human amnion (HA) cells. Large syncytia formed in these cells after infection with CMV; inclusion bodies were observed in the nuclei, and CMV antigens were demonstrated in both the cytoplasm and the nucleus by indirect immunofluorescence techniques. The synthesis of virus DNA was also detected, and the production of infectious virus was followed. The titers were lower (from 10(4) to 6 X 10(5) using different isolates of CMV) than those obtained in human embryo fibroblast (HEF) cells, and the replication cycle was slower in HA than in HEF cells.", "contents": "Infection of human amnion cells with cytomegalovirus. Human cytomegalovirus (CMV), known to replicate in vitro in human fibroblastic cells, was found to replicate in epithelial human amnion (HA) cells. Large syncytia formed in these cells after infection with CMV; inclusion bodies were observed in the nuclei, and CMV antigens were demonstrated in both the cytoplasm and the nucleus by indirect immunofluorescence techniques. The synthesis of virus DNA was also detected, and the production of infectious virus was followed. The titers were lower (from 10(4) to 6 X 10(5) using different isolates of CMV) than those obtained in human embryo fibroblast (HEF) cells, and the replication cycle was slower in HA than in HEF cells."}
{"id": "PMID:215717", "title": "Developments in viral hepatitis.", "content": "Viral hepatitis is a major public health problem occurring endemically in all parts of the world. The general term viral hepatitis refers to infections caused by hepatitis virus type A, type B and a more recently identified infection referred to as \"non-A: non-B\" hepatitis. These clinically and pathologically similar forms of hepatitis have been studied intensively following the discovery of a specific antigen, Australia antigen, one of the markers of infection with hepatitis B virus.", "contents": "Developments in viral hepatitis. Viral hepatitis is a major public health problem occurring endemically in all parts of the world. The general term viral hepatitis refers to infections caused by hepatitis virus type A, type B and a more recently identified infection referred to as \"non-A: non-B\" hepatitis. These clinically and pathologically similar forms of hepatitis have been studied intensively following the discovery of a specific antigen, Australia antigen, one of the markers of infection with hepatitis B virus."}
{"id": "PMID:215718", "title": "Rat tracheal organ culture supports replication of parainfluenza 1 (6/94) virus and promotes 6/94 virus rescue from latently infected human brain cells.", "content": "Rat tracheal organ culture (TOC) supported replication of parainfluenza 1 (6/94) virus. Cell-associated and cell-free viruses were found after primary infection of TOC. In contrast to other mammalian systems, rat TOC was capable of maintaining 6/94 virus infectivity after primary infection. Rat TOC may be considered a potential indicator system that could be used to detect virus latent in human tissue.", "contents": "Rat tracheal organ culture supports replication of parainfluenza 1 (6/94) virus and promotes 6/94 virus rescue from latently infected human brain cells. Rat tracheal organ culture (TOC) supported replication of parainfluenza 1 (6/94) virus. Cell-associated and cell-free viruses were found after primary infection of TOC. In contrast to other mammalian systems, rat TOC was capable of maintaining 6/94 virus infectivity after primary infection. Rat TOC may be considered a potential indicator system that could be used to detect virus latent in human tissue."}
{"id": "PMID:215719", "title": "Potentiation of coxsackievirus B3 infection in adult mice pretreated with a gold salt.", "content": "In mice treated with sodium aurothiomalate (myocrisin), prior to infection with Coxsackievirus B3, 90% of the animals died by the 11th day postinfection (p.i.). A mortality of 10% was noted in mice receiving myocrisin only, and no deaths occurred in animals infected with virus alone. The highest amount of virus was recovered from the pancreas of myocrisin-treated mice on day 3 p.i. This was over 500-fold higher than the virus titer found in the pancreas of mice infected with virus only. Generally the titer of virus present in different organs was higher at every point in drug-treated animals as compared to intact mice infected with the virus. A high and persistent viremia was present in myocrisin-treated mice; in contrast a low viremia followed by virus clearance from the blood was observed in intact mice infected with the virus. The antibody response was studied in intact and myocrisin-treated mice infected with the virus. In both groups, no neutralizing antibodies were detected on days 1, 2, and 3 p.i. On day 7 after infection, the titers of antibodies were 1:16 and 1:12 in intact and myocrisin-treated mice, respectively. Administration of hyperimmune anti-Coxsackievirus B3 serum 6 hours after infection protrected in myocrisin-treated group of mice against lethal disease. The results of these studies suggest that (1) antibodies alone may not be sufficient to limit the spread and persistence of virus in natural infections and (2) in the absence of any apparent histopathological differences the increased multiplication of Coxsackievirus B3 could be the cause of death in myocrisin-treated mice.", "contents": "Potentiation of coxsackievirus B3 infection in adult mice pretreated with a gold salt. In mice treated with sodium aurothiomalate (myocrisin), prior to infection with Coxsackievirus B3, 90% of the animals died by the 11th day postinfection (p.i.). A mortality of 10% was noted in mice receiving myocrisin only, and no deaths occurred in animals infected with virus alone. The highest amount of virus was recovered from the pancreas of myocrisin-treated mice on day 3 p.i. This was over 500-fold higher than the virus titer found in the pancreas of mice infected with virus only. Generally the titer of virus present in different organs was higher at every point in drug-treated animals as compared to intact mice infected with the virus. A high and persistent viremia was present in myocrisin-treated mice; in contrast a low viremia followed by virus clearance from the blood was observed in intact mice infected with the virus. The antibody response was studied in intact and myocrisin-treated mice infected with the virus. In both groups, no neutralizing antibodies were detected on days 1, 2, and 3 p.i. On day 7 after infection, the titers of antibodies were 1:16 and 1:12 in intact and myocrisin-treated mice, respectively. Administration of hyperimmune anti-Coxsackievirus B3 serum 6 hours after infection protrected in myocrisin-treated group of mice against lethal disease. The results of these studies suggest that (1) antibodies alone may not be sufficient to limit the spread and persistence of virus in natural infections and (2) in the absence of any apparent histopathological differences the increased multiplication of Coxsackievirus B3 could be the cause of death in myocrisin-treated mice."}
{"id": "PMID:215720", "title": "A case of Coxsackie A9 virus infection with orchitis.", "content": "A thirteen-year-old boy with bilateral orchitis was diagnosed as being infected by Coxsackie A9 virus by isolation of the virus from a throat swab and a fecal specimen. Serologic investigations revealed the development of transitory specific neutralizing IgM antibodies against the isotate and of persistent antibodies belonging to the other immunoglobulin classes. An etiology of the orchitis by any of the infectious agents usually found with this condition could be excluded.", "contents": "A case of Coxsackie A9 virus infection with orchitis. A thirteen-year-old boy with bilateral orchitis was diagnosed as being infected by Coxsackie A9 virus by isolation of the virus from a throat swab and a fecal specimen. Serologic investigations revealed the development of transitory specific neutralizing IgM antibodies against the isotate and of persistent antibodies belonging to the other immunoglobulin classes. An etiology of the orchitis by any of the infectious agents usually found with this condition could be excluded."}
{"id": "PMID:215721", "title": "Reduction of herpes simplex virus-type 2 plaque formation by urea.", "content": "The effect of urea on plaque formation by herpes simplex virus type 2 (HSV-2) was examined in two systems at concentrations within or approximating the range found in human urine. Approximately 7--10 mg urea/ml, added 2, 4, or 8 hours after infection, reduced plaque formation by 50% in African green monkey kidney cells. The growth of this system was affected slightly by continuous treatment with urea at 7--10 mg/ml. Plaque formation was reduced in the monkey kidney system, albeit diminishingly, even after addition of urea 12 hours after infection. In the human lung fibroblast system, urea at 10 mg/ml reduced plaque numbers by 50% but depressed the growth of cells completely.", "contents": "Reduction of herpes simplex virus-type 2 plaque formation by urea. The effect of urea on plaque formation by herpes simplex virus type 2 (HSV-2) was examined in two systems at concentrations within or approximating the range found in human urine. Approximately 7--10 mg urea/ml, added 2, 4, or 8 hours after infection, reduced plaque formation by 50% in African green monkey kidney cells. The growth of this system was affected slightly by continuous treatment with urea at 7--10 mg/ml. Plaque formation was reduced in the monkey kidney system, albeit diminishingly, even after addition of urea 12 hours after infection. In the human lung fibroblast system, urea at 10 mg/ml reduced plaque numbers by 50% but depressed the growth of cells completely."}
{"id": "PMID:215722", "title": "Effects of antidepressant agents on the synthesis of brain monoamines.", "content": "The effect of seventeen established or possible antidepressant agents on the synthesis of 5-HT, noradrenaline and dopamine in rat brain has been investigated by measuring the accumulation of 5-hydroxytryptophan and DOPA induced by an inhibitor of the aromatic L-aminoacid decarboxylase (3-hydroxybenzylhydrazine hydrochloride, 100 mg/kg i.p.). All the established inhibitors of 5-HT, noradrenaline and dopamine uptake were found to inhibit the synthesis of the respective monoamines, presumably by influencing a receptor-mediated feedback mechanism. A close correlation appears to exist between blockade of transmitter uptake and inhibition of transmitter synthesis. The results support current ideas on the mode of action of antidepressant agents.", "contents": "Effects of antidepressant agents on the synthesis of brain monoamines. The effect of seventeen established or possible antidepressant agents on the synthesis of 5-HT, noradrenaline and dopamine in rat brain has been investigated by measuring the accumulation of 5-hydroxytryptophan and DOPA induced by an inhibitor of the aromatic L-aminoacid decarboxylase (3-hydroxybenzylhydrazine hydrochloride, 100 mg/kg i.p.). All the established inhibitors of 5-HT, noradrenaline and dopamine uptake were found to inhibit the synthesis of the respective monoamines, presumably by influencing a receptor-mediated feedback mechanism. A close correlation appears to exist between blockade of transmitter uptake and inhibition of transmitter synthesis. The results support current ideas on the mode of action of antidepressant agents."}
{"id": "PMID:215727", "title": "Painful legs and moving toes: evidence on the site of the lesion.", "content": "A condition of painful legs with moving toes was described in 1971. Further examples of this condition are now reported, showing lesions in the posterior root ganglion, cauda equina, nerve roots, or a peripheral nerve of the lower limb. It is concluded that this syndrome is caused by a lesion of the afferent fibres of the posterior nerve roots. It is likely that this lesion causes frequent spontaneous impulses in the posterior roots which activate local circuits of interneurones and motoneurones and result in co-ordinated movements involving local muscles.", "contents": "Painful legs and moving toes: evidence on the site of the lesion. A condition of painful legs with moving toes was described in 1971. Further examples of this condition are now reported, showing lesions in the posterior root ganglion, cauda equina, nerve roots, or a peripheral nerve of the lower limb. It is concluded that this syndrome is caused by a lesion of the afferent fibres of the posterior nerve roots. It is likely that this lesion causes frequent spontaneous impulses in the posterior roots which activate local circuits of interneurones and motoneurones and result in co-ordinated movements involving local muscles."}
{"id": "PMID:215728", "title": "Muscle hypertrophy with neuropathy.", "content": "A patient with insidious onset of weakness, muscle atrophy and true hypertrophy, and sustained spasms is described. The spasms, initially mistaken to be myotonic, were shown electromyographically to result from sustained activity of the muscle fibres. An additional clinical manifestation verified myographically, was impaired reciprocal inhibition. Also, the patient had thick peripheral nerves and very slow motor (but normal sensory) nerve conduction. Histologic examination of sural nerve biopsy revealed large vacuoles within Schwann cells containing unidentified material, as well as onion-bulb formations. The possibility of a metabolic error resulting in storage of an abnormal material within Schwann cells is assumed.", "contents": "Muscle hypertrophy with neuropathy. A patient with insidious onset of weakness, muscle atrophy and true hypertrophy, and sustained spasms is described. The spasms, initially mistaken to be myotonic, were shown electromyographically to result from sustained activity of the muscle fibres. An additional clinical manifestation verified myographically, was impaired reciprocal inhibition. Also, the patient had thick peripheral nerves and very slow motor (but normal sensory) nerve conduction. Histologic examination of sural nerve biopsy revealed large vacuoles within Schwann cells containing unidentified material, as well as onion-bulb formations. The possibility of a metabolic error resulting in storage of an abnormal material within Schwann cells is assumed."}
{"id": "PMID:215729", "title": "Computerized double-tracer subtraction scanning with gallium-67 citrate in inflammatory diseases.", "content": "A gallium-67/technetium-99m subtraction technique was used with a variable weighting factor. That is, each image was separately set to 100%. Varying amounts of the Tc-99m images were subtracted from those of Ga-67. A total of 95 patients who had radiogallium scanning for suspected inflammatory disease were studied by the subtraction technique. Thirty of these patients had abnormal Tc-99m pyrophosphate bone scans, while 20 had abnormal radiogallium abdominal foci; 45 had defects in liver, spleen, or kidney images. The subtraction technique with variable weighting was highly successful in enhancing hot-spot visibility, and in providing information as to the anatomic location of the defect.", "contents": "Computerized double-tracer subtraction scanning with gallium-67 citrate in inflammatory diseases. A gallium-67/technetium-99m subtraction technique was used with a variable weighting factor. That is, each image was separately set to 100%. Varying amounts of the Tc-99m images were subtracted from those of Ga-67. A total of 95 patients who had radiogallium scanning for suspected inflammatory disease were studied by the subtraction technique. Thirty of these patients had abnormal Tc-99m pyrophosphate bone scans, while 20 had abnormal radiogallium abdominal foci; 45 had defects in liver, spleen, or kidney images. The subtraction technique with variable weighting was highly successful in enhancing hot-spot visibility, and in providing information as to the anatomic location of the defect."}
{"id": "PMID:215730", "title": "Vitamin E and lipoprotein levels in the sera of pregnant women.", "content": "The serum levels of vitamin E, cholesterol and lipoproteins, alpha1-lipoproteins and beta-lipoproteins in pregnant women were investigated. It was found that serum vitamin E, cholesterol and the lipoproteins had a tendency to increase throughout gestation. The mean serum alpha1-lipoprotein concentration was higher in pregnant women than in healthy control women. The ratios of the vitamin E concentration to the sum of alpha1-lipoproteins and beta-lipoproteins concentration in sera was constant. Furthermore, it was  found that serum vitamin E was correlated closely to the lipoprotein content (r = 0.814, p less than 0.001), except in a few subjects with abnormally high vitamin E levels.", "contents": "Vitamin E and lipoprotein levels in the sera of pregnant women. The serum levels of vitamin E, cholesterol and lipoproteins, alpha1-lipoproteins and beta-lipoproteins in pregnant women were investigated. It was found that serum vitamin E, cholesterol and the lipoproteins had a tendency to increase throughout gestation. The mean serum alpha1-lipoprotein concentration was higher in pregnant women than in healthy control women. The ratios of the vitamin E concentration to the sum of alpha1-lipoproteins and beta-lipoproteins concentration in sera was constant. Furthermore, it was  found that serum vitamin E was correlated closely to the lipoprotein content (r = 0.814, p less than 0.001), except in a few subjects with abnormally high vitamin E levels."}
{"id": "PMID:215733", "title": "Non-fibrous mineral dusts and malignant tumors: an epidemiological study of mortality.", "content": "The connection between enhanced oncological risk and the exposure to non-fibrous mineral dusts receives a contradictory but mostly negative estimation in the literature. The present authors estimated the death rate by relating the number of deaths from cancer, registered at different companies during a 21 to 27-year span, to the number of man-years of work for all employees during the same period. The death rates, calculated as above, were compared with the age standardized analogous death rates of the control population. The ratio of these indices, which statistically significantly exceeded 1.0, was taken as evidence of risk connected with exposure to the industrial environment. Frequency of registration of deaths from malignant tumors among other causes of death of silicotic patients was also studied. The results are in favor of accepting talc dust (even that not containing fibrous minerals) as a carcinogen, and silica containing dust only as a cocarcinogenic agent. The percent silica content in dust either plays no role at all, or plays a much lesser role than the total dust load. Tbc as the competing cause of death in silicotic patients, in grave forms of the disease, eliminates the susceptibility of patients to death from cancer.", "contents": "Non-fibrous mineral dusts and malignant tumors: an epidemiological study of mortality. The connection between enhanced oncological risk and the exposure to non-fibrous mineral dusts receives a contradictory but mostly negative estimation in the literature. The present authors estimated the death rate by relating the number of deaths from cancer, registered at different companies during a 21 to 27-year span, to the number of man-years of work for all employees during the same period. The death rates, calculated as above, were compared with the age standardized analogous death rates of the control population. The ratio of these indices, which statistically significantly exceeded 1.0, was taken as evidence of risk connected with exposure to the industrial environment. Frequency of registration of deaths from malignant tumors among other causes of death of silicotic patients was also studied. The results are in favor of accepting talc dust (even that not containing fibrous minerals) as a carcinogen, and silica containing dust only as a cocarcinogenic agent. The percent silica content in dust either plays no role at all, or plays a much lesser role than the total dust load. Tbc as the competing cause of death in silicotic patients, in grave forms of the disease, eliminates the susceptibility of patients to death from cancer."}
{"id": "PMID:215734", "title": "Pancreatic adenomas in infants and children: current surgical management.", "content": "Islet cell adenomas are an important consideration in infants and children with hypoglycemia due to hyperinsulinism. Between 1965 and 1977, 32 patients with hyperinsulinism were seen at the Children's Hospital of Philadelphia. Sixteen of these patients underwent surgery. Eight patients had single pancreatic adenomas, 5 of whom were infants under 1 yr of age. In 3 infants an adenoma was recognized and removed at the time of surgery. In 4 patients a subtotal pancreatectomy was successful in removing the adenoma. One infant is whom the adenoma was not included in the subtotal pancreatectomy died postoperatively with intractable hypoglycemia. Of the 7 patients cured by surgery, 6 are normal and 1 has brain damage due to delay in treatment of hypoglycemia. One child has mild diabetes. A combined medical and surgical protocol has been developed that permits rapid diagnosis of hyperinsulinism and selection of candidates for surgery. Infants under 1 yr of age who fail to respond to diazoxide should be explored. In children whose hyperinsulinism appears beyond 1 yr of age, surgery is indicated, since an adenoma is likely.", "contents": "Pancreatic adenomas in infants and children: current surgical management. Islet cell adenomas are an important consideration in infants and children with hypoglycemia due to hyperinsulinism. Between 1965 and 1977, 32 patients with hyperinsulinism were seen at the Children's Hospital of Philadelphia. Sixteen of these patients underwent surgery. Eight patients had single pancreatic adenomas, 5 of whom were infants under 1 yr of age. In 3 infants an adenoma was recognized and removed at the time of surgery. In 4 patients a subtotal pancreatectomy was successful in removing the adenoma. One infant is whom the adenoma was not included in the subtotal pancreatectomy died postoperatively with intractable hypoglycemia. Of the 7 patients cured by surgery, 6 are normal and 1 has brain damage due to delay in treatment of hypoglycemia. One child has mild diabetes. A combined medical and surgical protocol has been developed that permits rapid diagnosis of hyperinsulinism and selection of candidates for surgery. Infants under 1 yr of age who fail to respond to diazoxide should be explored. In children whose hyperinsulinism appears beyond 1 yr of age, surgery is indicated, since an adenoma is likely."}
{"id": "PMID:215736", "title": "Reimplantation of the ampulla of Vater after total pancreatectomy for nesidioblastosis.", "content": "Total pancreatectomy is often required to control hypoglycemic seizures in infants with nesidioblastosis. If duodenal devascularization results, reconstruction is difficult because standard biliary-intestinal anastomoses may reflux, or, in infants, become strictured. Therefore, surgeons are loath to perform such procedures. To avoid these complications, the common bile duct and the ampulla of Vater were implanted into the reconstructed duodenum.", "contents": "Reimplantation of the ampulla of Vater after total pancreatectomy for nesidioblastosis. Total pancreatectomy is often required to control hypoglycemic seizures in infants with nesidioblastosis. If duodenal devascularization results, reconstruction is difficult because standard biliary-intestinal anastomoses may reflux, or, in infants, become strictured. Therefore, surgeons are loath to perform such procedures. To avoid these complications, the common bile duct and the ampulla of Vater were implanted into the reconstructed duodenum."}
{"id": "PMID:215737", "title": "Preoperative angiographic embolization for large hemorrhagic Wilms' tumor.", "content": "Preoperative angiographic embolization of the renal artery is a surgical adjunct not necessary for the majority of Wilms' tumors. However, on the basis of early experience, we would recommend this technique for those large vascular tumors with preoperative hemorrhage in which the risk of embolization is likely to outweight the risk of intraoperative disruption and hemorrhage.", "contents": "Preoperative angiographic embolization for large hemorrhagic Wilms' tumor. Preoperative angiographic embolization of the renal artery is a surgical adjunct not necessary for the majority of Wilms' tumors. However, on the basis of early experience, we would recommend this technique for those large vascular tumors with preoperative hemorrhage in which the risk of embolization is likely to outweight the risk of intraoperative disruption and hemorrhage."}
{"id": "PMID:215741", "title": "The pharmacology of 2,3-dimercaptosuccinic acid and its potential use in arsenic poisoning.", "content": "Arsenic (As2O3)-poisoned rats were treated with either 2,3-dimercaptosuccinic acid (DMS) or dimercaptopropanol (BAL) at doses of 30 mg/kg/day. A control group received no treatment. The total quantity of arsenic excreted was not significantly different in response to 4 days of treatment with either DMS or BAL. In addition, there was no difference between the two drug treatment groups in the residual arsenic content of brain, liver, kidney and spleen after treatment. Both drugs reduced the arsenic content of each tissue to approximately 40% of that of untreated controls. Previous studies have shown that DMS is orally effective for the treatment of lead poisoning. The LD50 of DMS was determined to be in excess of 3 g/kg in rats and mice, approximately 30 times the LD50 of BAL. No gross, histopathological or biochemical evidence of toxicity was observed in mice, rats or dogs which received DMS 5 days per week for 6 months. DMS did not affect the excretion of zinc, iron, calcium or magnesium. Urinary copper excretion was significantly elevated in response to 30 mg/kg of DMS, suggesting that the drug might also be useful for the treatment of Wilson's disease.", "contents": "The pharmacology of 2,3-dimercaptosuccinic acid and its potential use in arsenic poisoning. Arsenic (As2O3)-poisoned rats were treated with either 2,3-dimercaptosuccinic acid (DMS) or dimercaptopropanol (BAL) at doses of 30 mg/kg/day. A control group received no treatment. The total quantity of arsenic excreted was not significantly different in response to 4 days of treatment with either DMS or BAL. In addition, there was no difference between the two drug treatment groups in the residual arsenic content of brain, liver, kidney and spleen after treatment. Both drugs reduced the arsenic content of each tissue to approximately 40% of that of untreated controls. Previous studies have shown that DMS is orally effective for the treatment of lead poisoning. The LD50 of DMS was determined to be in excess of 3 g/kg in rats and mice, approximately 30 times the LD50 of BAL. No gross, histopathological or biochemical evidence of toxicity was observed in mice, rats or dogs which received DMS 5 days per week for 6 months. DMS did not affect the excretion of zinc, iron, calcium or magnesium. Urinary copper excretion was significantly elevated in response to 30 mg/kg of DMS, suggesting that the drug might also be useful for the treatment of Wilson's disease."}
{"id": "PMID:215743", "title": "Depression of spinal monosynaptic transmission by diethyl ether: quantal analysis of unitary synaptic potentials.", "content": "The site at which diethyl ether impairs transmission in the spinal monosynaptic pathway was studied by intracellular recording from lumbosacral motoneurons. The drug was administered by inhalation to spinal cats, in concentrations which produce surgical anesthesia. Ether had no significant effect on resting potential or input resistance of the cell membrane. It decreased the electrical excitability in some but not all motoneurons. This action may contribute to the depressant effects of ether. Monosynaptic excitatory postsynaptic potentials evoked by impulses in a single Ia afferent fiber (unitary EPSPs) of the triceps surae nerve were recorded from homonymous motoneurons. They were measured and their amplitude distribution was analyzed by a computer-aided procedure. The mean amplitude of the unitary EPSPs was 0.15 to 0.31 mV, and the mean number of transmitter quanta released by each impulse ranged from 1.5 to 4.1 before drug administration. Both values were decreased during inhalation of ether but recovered toward normal after the drug was discontinued. The mean amplitude of the EPSPs produced by one transmitter quantum was 0.08 to 0.15 mV and was not depressed during ether administration. It is concluded that either in anesthetic concentrations depresses synaptic potentials presynaptically by decreasing the amount of excitatory transmitter released, while leaving the chemosensitivity of the postsynaptic membrane unchanged.", "contents": "Depression of spinal monosynaptic transmission by diethyl ether: quantal analysis of unitary synaptic potentials. The site at which diethyl ether impairs transmission in the spinal monosynaptic pathway was studied by intracellular recording from lumbosacral motoneurons. The drug was administered by inhalation to spinal cats, in concentrations which produce surgical anesthesia. Ether had no significant effect on resting potential or input resistance of the cell membrane. It decreased the electrical excitability in some but not all motoneurons. This action may contribute to the depressant effects of ether. Monosynaptic excitatory postsynaptic potentials evoked by impulses in a single Ia afferent fiber (unitary EPSPs) of the triceps surae nerve were recorded from homonymous motoneurons. They were measured and their amplitude distribution was analyzed by a computer-aided procedure. The mean amplitude of the unitary EPSPs was 0.15 to 0.31 mV, and the mean number of transmitter quanta released by each impulse ranged from 1.5 to 4.1 before drug administration. Both values were decreased during inhalation of ether but recovered toward normal after the drug was discontinued. The mean amplitude of the EPSPs produced by one transmitter quantum was 0.08 to 0.15 mV and was not depressed during ether administration. It is concluded that either in anesthetic concentrations depresses synaptic potentials presynaptically by decreasing the amount of excitatory transmitter released, while leaving the chemosensitivity of the postsynaptic membrane unchanged."}
{"id": "PMID:215744", "title": "Opiate receptor agonists as modulators of gamma-aminobutyric acid turnover in the nucleus caudatus, globus pallidus and substantia nigra of the rat.", "content": "The injection of various doses of morphine, subcutaneously, or of beta-endorphin, intraventricularly, changes the turnover rate of gamma-aminobutyric acid (TRGABA) in the substantia nigra, globus pallidus and nucleus caudatus. The TRGABA decreases in N. caudatus but increases in globus pallidus and substantia nigra. These changes are dose related and can be inhibited by naltrexone. The increased TRGABA in globus pallidus elicited by these opioid receptor agonists may be associated with catalepsy since muscimol, a specific GABA receptor agonist, injected into the globus pallidus causes a dose-related catalepsy. Since this GABA receptor agonist injected into the substantia nigra fails to cause catalepsy, one can exclude that the increase in the TRGABA of substantia nigra elicited by opiate receptor agonists is operative in mediating the catalepsy elicited by opioids.", "contents": "Opiate receptor agonists as modulators of gamma-aminobutyric acid turnover in the nucleus caudatus, globus pallidus and substantia nigra of the rat. The injection of various doses of morphine, subcutaneously, or of beta-endorphin, intraventricularly, changes the turnover rate of gamma-aminobutyric acid (TRGABA) in the substantia nigra, globus pallidus and nucleus caudatus. The TRGABA decreases in N. caudatus but increases in globus pallidus and substantia nigra. These changes are dose related and can be inhibited by naltrexone. The increased TRGABA in globus pallidus elicited by these opioid receptor agonists may be associated with catalepsy since muscimol, a specific GABA receptor agonist, injected into the globus pallidus causes a dose-related catalepsy. Since this GABA receptor agonist injected into the substantia nigra fails to cause catalepsy, one can exclude that the increase in the TRGABA of substantia nigra elicited by opiate receptor agonists is operative in mediating the catalepsy elicited by opioids."}
{"id": "PMID:215746", "title": "Interaction between alpha adrenergic and serotonergic activation of canine saphenous veins.", "content": "Serotonin and norepinephrine produced concentration-dependent contractions of helical strips of canine saphenous veins. The contractile responses to both agonists were inhibited by the alpha adrenergic receptor blocking agent phentolamine. Tolazoline inhibited the contractile responses of canine saphenous veins to norepinephrine but augmented those to serotonin. Blockade of adrenergic neuronal reuptake with cocaine enhanced the sensitivity of the canine saphenous vein to serotonin, but did not suppress the inhibition by phentolamine of the contractile responses to this indolealkylamine. Serotonin-mediated venoconstriction was not secondary to release of norepinephrine since it was not accompanied by an increased release of [7-3H]-norepinephrine. These findings suggest that serotonin does not contract canine saphenous veins by stimulation of typical serotonergic receptors. The binding sites for serotonin and norepinephrine in cutaneous venous smooth muscle may share part of a common receptor complex, which triggers the contractile process. Alternatively, serotonin and norepinephrine may act at two different receptors to elicit contraction of canine saphenous veins.", "contents": "Interaction between alpha adrenergic and serotonergic activation of canine saphenous veins. Serotonin and norepinephrine produced concentration-dependent contractions of helical strips of canine saphenous veins. The contractile responses to both agonists were inhibited by the alpha adrenergic receptor blocking agent phentolamine. Tolazoline inhibited the contractile responses of canine saphenous veins to norepinephrine but augmented those to serotonin. Blockade of adrenergic neuronal reuptake with cocaine enhanced the sensitivity of the canine saphenous vein to serotonin, but did not suppress the inhibition by phentolamine of the contractile responses to this indolealkylamine. Serotonin-mediated venoconstriction was not secondary to release of norepinephrine since it was not accompanied by an increased release of [7-3H]-norepinephrine. These findings suggest that serotonin does not contract canine saphenous veins by stimulation of typical serotonergic receptors. The binding sites for serotonin and norepinephrine in cutaneous venous smooth muscle may share part of a common receptor complex, which triggers the contractile process. Alternatively, serotonin and norepinephrine may act at two different receptors to elicit contraction of canine saphenous veins."}
{"id": "PMID:215747", "title": "Studies on SK&F 29661, an organ-specific inhibitor of phenylethanolamine N-methyltransferase.", "content": "SK&F 29661 is an effective, reversible inhibitor of both central nervous system and adrenal phenylethanolamine N-methyl-transferase in vitro; its Ki values in our standard assay systems were 6 X 10(-7) M (central nervous system) and 3 X 10(-7) M (adrenal), respectively. In vivo, the drug inhibited the conversion of [3H]norepinephrine to [3H]epinephrine in the rat adrenal gland and upon chronic administration decreased the endogenous adrenal epinephrine/norepinephrine ratio in both the rat and squirrel monkey. SK&F 29661 did not, however, reduce rat brain stem PNMT activity after systemic administration; subsequent radioautographic studies indicated that the compound did not enter the central nervous system, presumably because of its high polarity. This drug may be useful in defining the physiological importance of peripheral phenylethanolamine N-methyltransferase inhibition.", "contents": "Studies on SK&F 29661, an organ-specific inhibitor of phenylethanolamine N-methyltransferase. SK&F 29661 is an effective, reversible inhibitor of both central nervous system and adrenal phenylethanolamine N-methyl-transferase in vitro; its Ki values in our standard assay systems were 6 X 10(-7) M (central nervous system) and 3 X 10(-7) M (adrenal), respectively. In vivo, the drug inhibited the conversion of [3H]norepinephrine to [3H]epinephrine in the rat adrenal gland and upon chronic administration decreased the endogenous adrenal epinephrine/norepinephrine ratio in both the rat and squirrel monkey. SK&F 29661 did not, however, reduce rat brain stem PNMT activity after systemic administration; subsequent radioautographic studies indicated that the compound did not enter the central nervous system, presumably because of its high polarity. This drug may be useful in defining the physiological importance of peripheral phenylethanolamine N-methyltransferase inhibition."}
{"id": "PMID:215748", "title": "Transmission blockade and stimulation of ganglionic adenylate cyclase by catecholamines.", "content": "Isolated rat superior cervical ganglia treated with isoproterenol and related drugs show an increase in ganglionic cyclic adenosine 3':5'-monophosphate (cAMP) and a block of transmission. For isoproterenol, the maximum increase in cAMP occurred at 1 X 10(-6) M, a concentration without effect on transmission. Approximately 5 X 10(-4) M isoproterenol was required to reduce the ganglionic compound action potential by 50%. Dopamine, in  contrast to isoproterenol, had no effect on the content of cAMP but depressed transmission. The maximum increase in cAMP produced by norepinephrine occurred with 5 X 10(-4) M, a concentration that reduced transmission by approximately 35%. The effects of isoproterenol on adenylate cyclase and transmission were prevented either by practolol (10(-4) M) or phentolamine (10(-5) M). Dopamine-induced blockade of transmission was antagonized by phentolamine (10(-5) M). Whereas the blockade of transmission by norepinephrine was antagonized by practolol (10(-5) M) or phentolamine (10(-5) M), the stimulation of adenylate cyclase by norepinephrine was prevented by practolol (10(-4) M) but not by phentolamine (10(-5) M). These results show that the blockade of transmission and stimulation of adenylate cyclase are unrelated in rat ganglia and that adrenergic receptor classification is ambiguous. The role of adenylate cyclase in ganglia is unclear.", "contents": "Transmission blockade and stimulation of ganglionic adenylate cyclase by catecholamines. Isolated rat superior cervical ganglia treated with isoproterenol and related drugs show an increase in ganglionic cyclic adenosine 3':5'-monophosphate (cAMP) and a block of transmission. For isoproterenol, the maximum increase in cAMP occurred at 1 X 10(-6) M, a concentration without effect on transmission. Approximately 5 X 10(-4) M isoproterenol was required to reduce the ganglionic compound action potential by 50%. Dopamine, in  contrast to isoproterenol, had no effect on the content of cAMP but depressed transmission. The maximum increase in cAMP produced by norepinephrine occurred with 5 X 10(-4) M, a concentration that reduced transmission by approximately 35%. The effects of isoproterenol on adenylate cyclase and transmission were prevented either by practolol (10(-4) M) or phentolamine (10(-5) M). Dopamine-induced blockade of transmission was antagonized by phentolamine (10(-5) M). Whereas the blockade of transmission by norepinephrine was antagonized by practolol (10(-5) M) or phentolamine (10(-5) M), the stimulation of adenylate cyclase by norepinephrine was prevented by practolol (10(-4) M) but not by phentolamine (10(-5) M). These results show that the blockade of transmission and stimulation of adenylate cyclase are unrelated in rat ganglia and that adrenergic receptor classification is ambiguous. The role of adenylate cyclase in ganglia is unclear."}
{"id": "PMID:215749", "title": "Effects of acute and continuous morphine administration on catecholamine-sensitive adenosine triphosphatase in mouse brain.", "content": "The catecholamine-stimulated adenosine triphosphatase (ATP-ase) activities in mouse brain synaptosomes were inhibited by morphine both in vitro and in vivo. Morphine up to 10(-3) M had no effect on basal ATPase activities but at 10(-4) M significantly inhibited dopamine-sensitive ATPase activities in vitro. The morphine effect was antagonized by an opiate antagonist, naloxone. The catecholamine-sensitive ATPase activities were also inhibited by acute administration of morphine. The inhibition was dose-dependent. However, naloxone partially antagonized the morphine inhibition of depamine-sensitive ATPase activity but not norepinephrine-sensitive ATPase activity. A significant decrease in the sensitivity of synaptosomal ATPase to catecholamines was observed in mice rendered tolerant by morphine pellet implantation. The Na+,K+-ATPase was more affected by morphine as compared to Mg++-ATPase activity. The dopamine-sensitive Na+,K+-ATPase activity was restored by 50% in precipitated withdrawal mouse brain synaptosomes. Norepinephrine-sensitive ATPase activity was also restored partially in precipitated withdrawal animals. These results suggest that in mouse brain synaptosomes morphine may be interacting with ATPase at or near the catecholamine-active sites.", "contents": "Effects of acute and continuous morphine administration on catecholamine-sensitive adenosine triphosphatase in mouse brain. The catecholamine-stimulated adenosine triphosphatase (ATP-ase) activities in mouse brain synaptosomes were inhibited by morphine both in vitro and in vivo. Morphine up to 10(-3) M had no effect on basal ATPase activities but at 10(-4) M significantly inhibited dopamine-sensitive ATPase activities in vitro. The morphine effect was antagonized by an opiate antagonist, naloxone. The catecholamine-sensitive ATPase activities were also inhibited by acute administration of morphine. The inhibition was dose-dependent. However, naloxone partially antagonized the morphine inhibition of depamine-sensitive ATPase activity but not norepinephrine-sensitive ATPase activity. A significant decrease in the sensitivity of synaptosomal ATPase to catecholamines was observed in mice rendered tolerant by morphine pellet implantation. The Na+,K+-ATPase was more affected by morphine as compared to Mg++-ATPase activity. The dopamine-sensitive Na+,K+-ATPase activity was restored by 50% in precipitated withdrawal mouse brain synaptosomes. Norepinephrine-sensitive ATPase activity was also restored partially in precipitated withdrawal animals. These results suggest that in mouse brain synaptosomes morphine may be interacting with ATPase at or near the catecholamine-active sites."}
{"id": "PMID:215756", "title": "Nervous release of vasoactive intestinal polypeptide in the gastrointestinal tract of cats: possible physiological implications.", "content": "1. The release of vasoactive intestinal polypeptide (VIP) into blood from the gastrointestinal tract was studied when eliciting autonomic nervous effects known to be mediated via non-adrenergic, non-cholinergic nerve fibres. All studies were performed on animals given atropine. 2. Electrical stimulation of the low threshold vagal fibres to the stomach did not significantly change gastric volume or VIP concentration in the venous effluent from the stomach. Stimulating the high threshold fibres, on the other hand, produced a gastric relaxation concomitant with a significant increase of venous plasma VIP concentrations. When eliciting a similar vagal relaxation of the stomach by distending a balloon the oesophagus a significant increase of venous plasma VIP concentration was also recorded. 3. Mechanical stimulation of the mucosa of the small bowel increased intestinal blood flow and a significant increase of venous plasma VIP concentration was observed. 4. Stimulation of the pelvic nerves to the colon produced a transient vasodilation and a significant increase of VIP in the venous effluent from the large bowel. A maintained vasodilation in the colon was induced by mechanically stimulating the rectal mucosa. This vascular response was accompanied by a significant raise of venous plasma VIP concentration. 5. The results demonstrate that all the studied nervous effects known to be mediated via non-adrenergic, non-cholinergic nerve fibres were accompanied by significant increases of the VIP concentration in the venous effluent. The possible physiological implications of these findings are discussed and it is proposed that VIP may be a neurotransmitter in the gastrointestinal tract.", "contents": "Nervous release of vasoactive intestinal polypeptide in the gastrointestinal tract of cats: possible physiological implications. 1. The release of vasoactive intestinal polypeptide (VIP) into blood from the gastrointestinal tract was studied when eliciting autonomic nervous effects known to be mediated via non-adrenergic, non-cholinergic nerve fibres. All studies were performed on animals given atropine. 2. Electrical stimulation of the low threshold vagal fibres to the stomach did not significantly change gastric volume or VIP concentration in the venous effluent from the stomach. Stimulating the high threshold fibres, on the other hand, produced a gastric relaxation concomitant with a significant increase of venous plasma VIP concentrations. When eliciting a similar vagal relaxation of the stomach by distending a balloon the oesophagus a significant increase of venous plasma VIP concentration was also recorded. 3. Mechanical stimulation of the mucosa of the small bowel increased intestinal blood flow and a significant increase of venous plasma VIP concentration was observed. 4. Stimulation of the pelvic nerves to the colon produced a transient vasodilation and a significant increase of VIP in the venous effluent from the large bowel. A maintained vasodilation in the colon was induced by mechanically stimulating the rectal mucosa. This vascular response was accompanied by a significant raise of venous plasma VIP concentration. 5. The results demonstrate that all the studied nervous effects known to be mediated via non-adrenergic, non-cholinergic nerve fibres were accompanied by significant increases of the VIP concentration in the venous effluent. The possible physiological implications of these findings are discussed and it is proposed that VIP may be a neurotransmitter in the gastrointestinal tract."}
{"id": "PMID:215757", "title": "Facilitation of synaptic transmission by general anaesthetics.", "content": "1. The actions of five structurally different intravenous and inhalation anaesthetics (alphaxalone/alphadolone, halothane, ketamine, methohexitone, and pentobarbitone) have been studied on synaptic transmission through the cuneate nucleus of the dorsal column-lemniscal afferent pathway in the decerebrate cat. 2. Synaptic input and output were estimated from antidromic and orthodromic potentials, which were evoked by either afferent volleys from the periphery or micro-electrode excitation of the presynaptic fibre terminals in the cuneate and recorded at forelimb nerves and the medial lemniscus. 3. Each of the anaesthetic agents potentiated the efficiency of synaptic transmission, as shown by the elevation of input-output curves constructed from the integrals of the potentials evoked by varying intensities of either peripheral or cuneate stimulation. 4. The excitability of the afferent terminals, as measured at the peripheral nerves by the antidromic responses to micro-electrode stimulation, was depressed by the anaesthetics. Post-synaptic excitability, which was assessed from the direct lemniscal response to intra-nuclear stimulation, did not appear to change. 5. Hypotensive states (mean arterial levels less than 60 torr) produced depolarization of presynaptic terminals and depression of synaptic efficiency and transmission; these changes opposed the primary effects of the general anaesthetics. 6. It is concluded that anaesthetics do not depress activity at all synapses of the central nervous system. Their facilitatory action on cuneate transmission is attributed to an enhanced release of excitatory transmitter; the underlying mechanism may be hyperpolarization of the primary afferent terminals, secondary to an increase in K+ conductance.", "contents": "Facilitation of synaptic transmission by general anaesthetics. 1. The actions of five structurally different intravenous and inhalation anaesthetics (alphaxalone/alphadolone, halothane, ketamine, methohexitone, and pentobarbitone) have been studied on synaptic transmission through the cuneate nucleus of the dorsal column-lemniscal afferent pathway in the decerebrate cat. 2. Synaptic input and output were estimated from antidromic and orthodromic potentials, which were evoked by either afferent volleys from the periphery or micro-electrode excitation of the presynaptic fibre terminals in the cuneate and recorded at forelimb nerves and the medial lemniscus. 3. Each of the anaesthetic agents potentiated the efficiency of synaptic transmission, as shown by the elevation of input-output curves constructed from the integrals of the potentials evoked by varying intensities of either peripheral or cuneate stimulation. 4. The excitability of the afferent terminals, as measured at the peripheral nerves by the antidromic responses to micro-electrode stimulation, was depressed by the anaesthetics. Post-synaptic excitability, which was assessed from the direct lemniscal response to intra-nuclear stimulation, did not appear to change. 5. Hypotensive states (mean arterial levels less than 60 torr) produced depolarization of presynaptic terminals and depression of synaptic efficiency and transmission; these changes opposed the primary effects of the general anaesthetics. 6. It is concluded that anaesthetics do not depress activity at all synapses of the central nervous system. Their facilitatory action on cuneate transmission is attributed to an enhanced release of excitatory transmitter; the underlying mechanism may be hyperpolarization of the primary afferent terminals, secondary to an increase in K+ conductance."}
{"id": "PMID:215758", "title": "Role of joint afferents in motor control exemplified by effects on reflex pathways from Ib afferents.", "content": "1. Intracellular recording from motoneurones to hind limb muscles in the cat was used to investigate the effect of volleys in the posterior nerve to the knee joint on motoneurones and on transmission from Ib afferents. 2. Volleys in the joint nerve facilitate transmission in disynaptic and trisynaptic inhibitory and excitatory reflex pathways from Ib afferents. It is postulated that facilitation, which appears at a strength of 1.5 times threshold, is evoked, not by Ib afferents which 'contaminate' the joint nerve, but by afferents from joints receptors. 3. T;e time course of facilitation of the disynaptic Ib i.p.s.p.s in motoneurones indicates that these joint afferents have disynaptic connexions with the interneurones of the Ib inhibitory pathway. 4. A brief description is given of synaptic effects evoked in motoneurones by graded electrical stimulation of the posterior nerve to the knee joint. At low stimulus strength the effects may be evoked via interneurones of Ib reflex pathways, but some results suggest that other interneuronal paths are utilized as well. Somewhat higher strengths, but occasionally less than 2 times threshold, produce later synaptic effects presumably mediated by reflex paths from the flexor reflex afferents; it does not seem likely that the contributory afferents in the joint nerve have nociceptive function. 5. It is suggested that impulses from impulses from joint receptors can influence tension regulation from Golgi tendon organs; if these receptors are activated in the terminal phase of the movement they may contribute a purposeful decrease of tension. It is pointed out that joint receptors may have an important role in motor regulation by their effects on interneurones of the different neuronal systems controlling motoneurones.", "contents": "Role of joint afferents in motor control exemplified by effects on reflex pathways from Ib afferents. 1. Intracellular recording from motoneurones to hind limb muscles in the cat was used to investigate the effect of volleys in the posterior nerve to the knee joint on motoneurones and on transmission from Ib afferents. 2. Volleys in the joint nerve facilitate transmission in disynaptic and trisynaptic inhibitory and excitatory reflex pathways from Ib afferents. It is postulated that facilitation, which appears at a strength of 1.5 times threshold, is evoked, not by Ib afferents which 'contaminate' the joint nerve, but by afferents from joints receptors. 3. T;e time course of facilitation of the disynaptic Ib i.p.s.p.s in motoneurones indicates that these joint afferents have disynaptic connexions with the interneurones of the Ib inhibitory pathway. 4. A brief description is given of synaptic effects evoked in motoneurones by graded electrical stimulation of the posterior nerve to the knee joint. At low stimulus strength the effects may be evoked via interneurones of Ib reflex pathways, but some results suggest that other interneuronal paths are utilized as well. Somewhat higher strengths, but occasionally less than 2 times threshold, produce later synaptic effects presumably mediated by reflex paths from the flexor reflex afferents; it does not seem likely that the contributory afferents in the joint nerve have nociceptive function. 5. It is suggested that impulses from impulses from joint receptors can influence tension regulation from Golgi tendon organs; if these receptors are activated in the terminal phase of the movement they may contribute a purposeful decrease of tension. It is pointed out that joint receptors may have an important role in motor regulation by their effects on interneurones of the different neuronal systems controlling motoneurones."}
{"id": "PMID:215768", "title": "The use of cattle to protect sheep from bluetongue infection.", "content": "Studies on the host preferences of Culicoides imicola, the vector of bluetongue virus in South Africa, are reviewed. There is agreement that this species prefers to feed on cattle but will also feed on other bovidae and sheep. Over a seven year period cattle kept near sheep on a Natal farm appear to have appreciably reduced the incidence of bluetongue in the sheep. In addition to immunization this \"decoy\" approach is therefore recommended to assist in the protection of stock from insect borne diseases such as bluetongue and possibly African horsesickness and Rift Valley fever.", "contents": "The use of cattle to protect sheep from bluetongue infection. Studies on the host preferences of Culicoides imicola, the vector of bluetongue virus in South Africa, are reviewed. There is agreement that this species prefers to feed on cattle but will also feed on other bovidae and sheep. Over a seven year period cattle kept near sheep on a Natal farm appear to have appreciably reduced the incidence of bluetongue in the sheep. In addition to immunization this \"decoy\" approach is therefore recommended to assist in the protection of stock from insect borne diseases such as bluetongue and possibly African horsesickness and Rift Valley fever."}
{"id": "PMID:215769", "title": "[Infectious causes of perinatal mortalities in ruminants (author's transl)].", "content": "The advantages and disadvantages of the different diagnostic techniques e.g. pathological and microbiological studies, immunoglobulin and specific antibody determinations and fluorescent antibody studies in relation to these mortalities are discussed. The most important pathological lesions in the placentas and foetuses are described.", "contents": "[Infectious causes of perinatal mortalities in ruminants (author's transl)]. The advantages and disadvantages of the different diagnostic techniques e.g. pathological and microbiological studies, immunoglobulin and specific antibody determinations and fluorescent antibody studies in relation to these mortalities are discussed. The most important pathological lesions in the placentas and foetuses are described."}
{"id": "PMID:215770", "title": "The mitochondria-rich cell of frog skin as hormone-sensitive \"shunt-path\".", "content": "Further investigations about the role of the mitochondria-rich cell (MR cell) in hormone-mediated transport regulation in the epithelium of frog skin brought the following results: Unlike toad bladder, in frog skin the spontaneous potential difference cannot be reversed when Na transport is blocked. A similar situation is obtained when, in addition to transport-blockade, one applies a chemical gradient for chloride to the epithelium. Under these conditions we found that in the intact preparation as well as in the separated epithelium: (i) the reversed current (RC) is linearly related to the number of MR cells; (ii) RC is mainly carried by a passive, transcellular chloride flux inwards and (iii) RC is sensitive to nor-adrenaline (10(-7) M). The beta-blocker propranolol abolishes this effect. We propose that the MR cells are the sites of transepithelial shunt-path and that this chloride flux is transcellular. As it is hormone sensitive, it could be an important regulatory instrument for the regulation of overall salt transport (internal shorting).", "contents": "The mitochondria-rich cell of frog skin as hormone-sensitive \"shunt-path\". Further investigations about the role of the mitochondria-rich cell (MR cell) in hormone-mediated transport regulation in the epithelium of frog skin brought the following results: Unlike toad bladder, in frog skin the spontaneous potential difference cannot be reversed when Na transport is blocked. A similar situation is obtained when, in addition to transport-blockade, one applies a chemical gradient for chloride to the epithelium. Under these conditions we found that in the intact preparation as well as in the separated epithelium: (i) the reversed current (RC) is linearly related to the number of MR cells; (ii) RC is mainly carried by a passive, transcellular chloride flux inwards and (iii) RC is sensitive to nor-adrenaline (10(-7) M). The beta-blocker propranolol abolishes this effect. We propose that the MR cells are the sites of transepithelial shunt-path and that this chloride flux is transcellular. As it is hormone sensitive, it could be an important regulatory instrument for the regulation of overall salt transport (internal shorting)."}
{"id": "PMID:215771", "title": "Role of prostaglandin E (PGE) in the modulation of the action of vasopressin on water flow in the urinary bladder of the toad and mammalian kidney.", "content": "PGE1 and PGE2 are known to interfere with the water permeability effect of vasopressin in toad bladder and kidney. It has been proposed that endogenous prostaglandin E (PGE), synthesized within cells of vasopressin-sensitive tissues, serves to modulate the permeability changes elicited by the neurohypophyseal hormone. Direct evidence in support of this hypothesis is as follows: vasopressin increases the biosynthesis of PGE2 in renal interstitial cells and in isolated toad bladder. In the latter, inhibition of vasopressin-induced synthesis of PGE by a variety of inhibitors results in a greater water permeability response to vasopressin. It appears that vasopressin has two effects in toad bladder and kidney: (i) it activates adenylate cyclase thereby increasing the concentration of adenosine 3',5' monophosphate  (cyclic AMP), the nucleotide responsible for the resultant increase in water permeability; and (ii) it activates a phospholipase that serves to release arachidonic acid, the precursor of PGE2 from intracellular pools. The PGE derived from the arachidonic acid diminishes adenylate-cyclase activity, in consequence of which the response of the enzyme to vasopressin is modulated.", "contents": "Role of prostaglandin E (PGE) in the modulation of the action of vasopressin on water flow in the urinary bladder of the toad and mammalian kidney. PGE1 and PGE2 are known to interfere with the water permeability effect of vasopressin in toad bladder and kidney. It has been proposed that endogenous prostaglandin E (PGE), synthesized within cells of vasopressin-sensitive tissues, serves to modulate the permeability changes elicited by the neurohypophyseal hormone. Direct evidence in support of this hypothesis is as follows: vasopressin increases the biosynthesis of PGE2 in renal interstitial cells and in isolated toad bladder. In the latter, inhibition of vasopressin-induced synthesis of PGE by a variety of inhibitors results in a greater water permeability response to vasopressin. It appears that vasopressin has two effects in toad bladder and kidney: (i) it activates adenylate cyclase thereby increasing the concentration of adenosine 3',5' monophosphate  (cyclic AMP), the nucleotide responsible for the resultant increase in water permeability; and (ii) it activates a phospholipase that serves to release arachidonic acid, the precursor of PGE2 from intracellular pools. The PGE derived from the arachidonic acid diminishes adenylate-cyclase activity, in consequence of which the response of the enzyme to vasopressin is modulated."}
{"id": "PMID:215772", "title": "Photoaffinity labeling of the antidiuretic hormone receptor.", "content": "A study to determine the feasibility of photoaffinity labeling the antidiuretic hormone receptor in the toad urinary bladder has been carried out. Two photoactivated derivatives of oxytocin have been synthesized, purified, and characterized chemically and biologically. Photolysis of the toad bladder in the presence of one of these derivatives, 2-nitro-5-azidobenzoylglycyloxytocin, produces a permanent inhibition of the response to native oxytocin. This inhibition can be relieved by protecting the hormone receptor with excess oxytocin during the photolysis. These results suggest that the photolysis-dependent inhibition of the response to native hormone is due to covalent incorporation of the photoaffinity label into the hormone receptor.", "contents": "Photoaffinity labeling of the antidiuretic hormone receptor. A study to determine the feasibility of photoaffinity labeling the antidiuretic hormone receptor in the toad urinary bladder has been carried out. Two photoactivated derivatives of oxytocin have been synthesized, purified, and characterized chemically and biologically. Photolysis of the toad bladder in the presence of one of these derivatives, 2-nitro-5-azidobenzoylglycyloxytocin, produces a permanent inhibition of the response to native oxytocin. This inhibition can be relieved by protecting the hormone receptor with excess oxytocin during the photolysis. These results suggest that the photolysis-dependent inhibition of the response to native hormone is due to covalent incorporation of the photoaffinity label into the hormone receptor."}
{"id": "PMID:215773", "title": "Characteristics of antibody inhibition of rat kidney (Na+ -K+)-ATPase.", "content": "Antibodies which were raised against highly purified membrane-bound (Na+ -K+)-ATPase from the outer medulla of rat kidneys inhibit the (Na+-K+)-ATPase activity up to 95%. The antibody inhibition is reversible. The time course of enzyme inhibition and reactivation is biphasic in semilogarithmic plots. In the purified membrane-bound (Na+-K+)-ATPase negative cooperativity was observed (a) for the ATP dependence of the (Na+ -K+)-ATPase activity (n = 0.86), (b) for the ATP binding to the enzyme (n = 0.58), and (c) for the ouabain inhibition of the (Na+ -K+)-ATPase activity (n = 0.77). By measuring the Na+ dependence of the (Na+ -K+)-ATPase reaction, a positive homotropic cooperativity (n = 1.67) was found. As reactivation of the antibody-inhibited enzyme proceeds very slowly (t0.5 = 5.2 hr), it was possible to measure characteristics of the antibody-(Na+ -K+)-ATPase complex: The antibodies exerted similar effects on the ATP dependence of the (Na+ -K+)-ATPase reaction and on the ATP binding of the enzyme. Vmax of the (Na+ -K+)-ATPase reaction and the number of ATP binding sites were reduced while K0.5 ATP for the (Na+ -K+)-ATPase activity and for the ATP binding were increased by the antibodies. The Hill coefficients for the ATP binding and for the ATP dependence of the enzyme activity were not significantly altered by the antibodies. The antibodies increased the K0.5 value for the Na+ stimulation of the (Na+ -K+)-ATPase activity, but they did not alter the homotropic interactions between the Na+-binding sites. The negative cooperativity which was observed for the ouabain inhibition of the (Na+ -K)-ATPase activity was abolished by the antibodies. The data are tentatively explained by the following model: The antibodies bind to the (Na+ -K+)-ATPase from the inner membrane side, reduce the ATP binding symmetrically at the ATP binding sites and reduce thereby also the (Na+ -K+)-ATPase activity of the enzyme. The antibodies may inhibit the ATP binding by a direct interaction or by means of a conformational change at the ATP binding sites. This may possibly also lead to the alteration of the Na+ dependence of the (Na+ -K+)-ATPase activity and to the observed alteration of the dose response to the ouabain inhibition.", "contents": "Characteristics of antibody inhibition of rat kidney (Na+ -K+)-ATPase. Antibodies which were raised against highly purified membrane-bound (Na+ -K+)-ATPase from the outer medulla of rat kidneys inhibit the (Na+-K+)-ATPase activity up to 95%. The antibody inhibition is reversible. The time course of enzyme inhibition and reactivation is biphasic in semilogarithmic plots. In the purified membrane-bound (Na+-K+)-ATPase negative cooperativity was observed (a) for the ATP dependence of the (Na+ -K+)-ATPase activity (n = 0.86), (b) for the ATP binding to the enzyme (n = 0.58), and (c) for the ouabain inhibition of the (Na+ -K+)-ATPase activity (n = 0.77). By measuring the Na+ dependence of the (Na+ -K+)-ATPase reaction, a positive homotropic cooperativity (n = 1.67) was found. As reactivation of the antibody-inhibited enzyme proceeds very slowly (t0.5 = 5.2 hr), it was possible to measure characteristics of the antibody-(Na+ -K+)-ATPase complex: The antibodies exerted similar effects on the ATP dependence of the (Na+ -K+)-ATPase reaction and on the ATP binding of the enzyme. Vmax of the (Na+ -K+)-ATPase reaction and the number of ATP binding sites were reduced while K0.5 ATP for the (Na+ -K+)-ATPase activity and for the ATP binding were increased by the antibodies. The Hill coefficients for the ATP binding and for the ATP dependence of the enzyme activity were not significantly altered by the antibodies. The antibodies increased the K0.5 value for the Na+ stimulation of the (Na+ -K+)-ATPase activity, but they did not alter the homotropic interactions between the Na+-binding sites. The negative cooperativity which was observed for the ouabain inhibition of the (Na+ -K)-ATPase activity was abolished by the antibodies. The data are tentatively explained by the following model: The antibodies bind to the (Na+ -K+)-ATPase from the inner membrane side, reduce the ATP binding symmetrically at the ATP binding sites and reduce thereby also the (Na+ -K+)-ATPase activity of the enzyme. The antibodies may inhibit the ATP binding by a direct interaction or by means of a conformational change at the ATP binding sites. This may possibly also lead to the alteration of the Na+ dependence of the (Na+ -K+)-ATPase activity and to the observed alteration of the dose response to the ouabain inhibition."}
{"id": "PMID:215775", "title": "Twice-a-day treatment in the radiotherapeutic management of malignant mixed tumor of the parotid gland: A case report.", "content": "A patient with a 2,300 gm malignant mixed tumor of the parotid gland had recurrence 19 days post surgery. The recurrent mass failed to respond to daily fractions of 200 rad conventional irradiation four times per week and actually increased in size. A superfractionation scheme was substituted, employing twice-a-day 200 rad at 4-5\u00bd hours intervals three times a week for 2\u00bd weeks. At the completion of treatment, there was a 50 percent regression of the recurrent tumor mass and a 100 percent regression two weeks post irradiation. A protocol using a twice-a-day treatment is discussed.", "contents": "Twice-a-day treatment in the radiotherapeutic management of malignant mixed tumor of the parotid gland: A case report. A patient with a 2,300 gm malignant mixed tumor of the parotid gland had recurrence 19 days post surgery. The recurrent mass failed to respond to daily fractions of 200 rad conventional irradiation four times per week and actually increased in size. A superfractionation scheme was substituted, employing twice-a-day 200 rad at 4-5\u00bd hours intervals three times a week for 2\u00bd weeks. At the completion of treatment, there was a 50 percent regression of the recurrent tumor mass and a 100 percent regression two weeks post irradiation. A protocol using a twice-a-day treatment is discussed."}
{"id": "PMID:215776", "title": "Peptide-chain initiation with Lsc poliovirus is intrinsically more resistant to hypertonic environment than is peptide-chain initiation with Mahoney virus and deletion mutants of Mahoney virus.", "content": "Peptide-chain initiation with LSc poliovirus was more resistant to hypertonic medium than peptide-chain initiation with Mahoney poliovirus. Protein synthesis of LSc virus retained its relative resistance to high osmolarity created by the addition of excess NaCl to the medium in cells coinfected with Mahoney virus. The data indicate that peptide-chain initiation with LSc virus is intrinsically more resistant to high osmolarity than that of Mahoney virus rather than reflecting different permeability changes in cells after infection. Two Mahoney virus mutants harboring deletions at the 5' end of the viral chromosome exhibited the same sensitivity to excess NaCl as parent virus, suggesting that the original chromosomal region for peptide-chain initiation has not been severely altered by the deletions.", "contents": "Peptide-chain initiation with Lsc poliovirus is intrinsically more resistant to hypertonic environment than is peptide-chain initiation with Mahoney virus and deletion mutants of Mahoney virus. Peptide-chain initiation with LSc poliovirus was more resistant to hypertonic medium than peptide-chain initiation with Mahoney poliovirus. Protein synthesis of LSc virus retained its relative resistance to high osmolarity created by the addition of excess NaCl to the medium in cells coinfected with Mahoney virus. The data indicate that peptide-chain initiation with LSc virus is intrinsically more resistant to high osmolarity than that of Mahoney virus rather than reflecting different permeability changes in cells after infection. Two Mahoney virus mutants harboring deletions at the 5' end of the viral chromosome exhibited the same sensitivity to excess NaCl as parent virus, suggesting that the original chromosomal region for peptide-chain initiation has not been severely altered by the deletions."}
{"id": "PMID:215777", "title": "Specific site of action for single-strand specific nuclease on the double-stranded circular DNA intermediates of an avian RNA tumor virus.", "content": "Circular viral DNA intermediates obtained from the quail tumor line, QT6, at 1 day after infection, were opened at one specific location by the single-strand specific nuclease, S1, of Aspergillus oryzae. This site was no longer accessible to the S1 nuclease when circles were first opened at another location with a restriction endonuclease.", "contents": "Specific site of action for single-strand specific nuclease on the double-stranded circular DNA intermediates of an avian RNA tumor virus. Circular viral DNA intermediates obtained from the quail tumor line, QT6, at 1 day after infection, were opened at one specific location by the single-strand specific nuclease, S1, of Aspergillus oryzae. This site was no longer accessible to the S1 nuclease when circles were first opened at another location with a restriction endonuclease."}
{"id": "PMID:215778", "title": "Detection of mouse mammary tumor virus RNA in BALB/c tumor cell lines of nonviral etiologies.", "content": "A complementary DNA (cDNA) probe to mouse mammary tumor virus (MMTV) RNA was synthesized using calf thymus DNA oligonucleotides as a random primer. This probe was then used to study the expression of MMTV RNA in cell lines from BALB/c tumors induced in vivo either spontaneously or in response to viral, chemical, or hormonal stimuli. The cDNA had a length of approximately 400 to 500 nucleotides and specifically hybridized to MMTV RNA and BALB/c lactating mammary gland RNA, but not to Moloney leukemia virus RNA. Calf thymus DNA-primed cDNA could protect 50% of iodinated MMTV RNA from S1 nuclease digestion at cDNA-RNA ratios of 1:1 and 90% of labeled viral RNA at ratios of 10:1. Thermal denaturation of MMTV RNA-cDNA hybrids yielded a T(m) of 88.5 degrees C, indicative of a well-base-paired duplex. Screening of mouse mammary tumor cells for MMTV sequences revealed that three out of five lines of BALB/c origin had undetectable levels of viral RNA (<three molecules per cell) by RNA excess hybridization. Two of the three \"virus-negative\" cell lines were derived from tumors induced by the chemical carcinogen 7,12-dimethylbenz(alpha)anthracene, whereas the third tumor occurred spontaneously. Two lines from tumors induced by either viral (mammary tumor virus) or hormonal (17-beta-estradiol) stimulus contained between three and nine molecules of MMTV RNA per cell by both RNA excess and cDNA excess hybridization. Clonal derivatives of these tumor lines had levels of viral RNA comparable to those of their parental lines. Therefore, it appears that the presence of detectable MMTV RNA sequences is not a necessary requirement for the maintenance of all murine mammary gland neoplasias.", "contents": "Detection of mouse mammary tumor virus RNA in BALB/c tumor cell lines of nonviral etiologies. A complementary DNA (cDNA) probe to mouse mammary tumor virus (MMTV) RNA was synthesized using calf thymus DNA oligonucleotides as a random primer. This probe was then used to study the expression of MMTV RNA in cell lines from BALB/c tumors induced in vivo either spontaneously or in response to viral, chemical, or hormonal stimuli. The cDNA had a length of approximately 400 to 500 nucleotides and specifically hybridized to MMTV RNA and BALB/c lactating mammary gland RNA, but not to Moloney leukemia virus RNA. Calf thymus DNA-primed cDNA could protect 50% of iodinated MMTV RNA from S1 nuclease digestion at cDNA-RNA ratios of 1:1 and 90% of labeled viral RNA at ratios of 10:1. Thermal denaturation of MMTV RNA-cDNA hybrids yielded a T(m) of 88.5 degrees C, indicative of a well-base-paired duplex. Screening of mouse mammary tumor cells for MMTV sequences revealed that three out of five lines of BALB/c origin had undetectable levels of viral RNA (<three molecules per cell) by RNA excess hybridization. Two of the three \"virus-negative\" cell lines were derived from tumors induced by the chemical carcinogen 7,12-dimethylbenz(alpha)anthracene, whereas the third tumor occurred spontaneously. Two lines from tumors induced by either viral (mammary tumor virus) or hormonal (17-beta-estradiol) stimulus contained between three and nine molecules of MMTV RNA per cell by both RNA excess and cDNA excess hybridization. Clonal derivatives of these tumor lines had levels of viral RNA comparable to those of their parental lines. Therefore, it appears that the presence of detectable MMTV RNA sequences is not a necessary requirement for the maintenance of all murine mammary gland neoplasias."}
{"id": "PMID:215779", "title": "Genomic stability of gibbon oncornavirus.", "content": "The 70S RNAs from several gibbon type C viruses were examined for sequence homology by molecular hybridization using complementary DNA probes. The sequence homology was found to vary with each virus isolate. The genome from one isolate was examined for genomic stability after the virus was experimentally passaged through three unrelated gibbons. The genomic homology remained unchanged after three passages, having greater than 93% homology based on complementary DNA-70S RNA hybridization and melting temperature analysis of the duplex. The genome from another isolate was similarly found to be unchanged after the virus was naturally transmitted in gibbons. The genomic variation found in the various isolates is not the consequence of recent horizontal transmission from a common virus.", "contents": "Genomic stability of gibbon oncornavirus. The 70S RNAs from several gibbon type C viruses were examined for sequence homology by molecular hybridization using complementary DNA probes. The sequence homology was found to vary with each virus isolate. The genome from one isolate was examined for genomic stability after the virus was experimentally passaged through three unrelated gibbons. The genomic homology remained unchanged after three passages, having greater than 93% homology based on complementary DNA-70S RNA hybridization and melting temperature analysis of the duplex. The genome from another isolate was similarly found to be unchanged after the virus was naturally transmitted in gibbons. The genomic variation found in the various isolates is not the consequence of recent horizontal transmission from a common virus."}
{"id": "PMID:215780", "title": "Transcription pattern of in vivo-labeled late simian virus 40 RNA: equimolar transcription beyond the mRNA 3' terminus.", "content": "We have examined the pattern of RNA transcription on the L (late) DNA strand late in the simian virus 40 virus infectious cycle by separating pulse-labeled RNA chains according to size and hybridizing to an ordered series of DNA fragments obtained by restriction enzyme digestion. From this analysis, the 5' end of the nascent transcript occurs a short distance counterclockwise from 0.735. Transcription proceeds in a clockwise direction. There is equimolar transcription for at least 1,000 nucleotides beyond the 3' end of the mRNA (0.175). The 3' terminus for the largest molecules is in 0.43--0.655. Molecules which represent more than one circuit of the genome are not more than 1% of the total population of nascent molecules. Implications of these findings for models of the biogenesis of mRNA are discussed.", "contents": "Transcription pattern of in vivo-labeled late simian virus 40 RNA: equimolar transcription beyond the mRNA 3' terminus. We have examined the pattern of RNA transcription on the L (late) DNA strand late in the simian virus 40 virus infectious cycle by separating pulse-labeled RNA chains according to size and hybridizing to an ordered series of DNA fragments obtained by restriction enzyme digestion. From this analysis, the 5' end of the nascent transcript occurs a short distance counterclockwise from 0.735. Transcription proceeds in a clockwise direction. There is equimolar transcription for at least 1,000 nucleotides beyond the 3' end of the mRNA (0.175). The 3' terminus for the largest molecules is in 0.43--0.655. Molecules which represent more than one circuit of the genome are not more than 1% of the total population of nascent molecules. Implications of these findings for models of the biogenesis of mRNA are discussed."}
{"id": "PMID:215781", "title": "Analysis of unintegrated avian RNA tumor virus double-stranded DNA intermediates.", "content": "Previous studies by Guntaka et al. have shown that the unintegrated DNA intermediates of avian RNA tumor virus replication can be readily isolated from cultures of the quail tumor line QT-6 at 1 day after infection. The intermediates include double-stranded linear and covalently closed circular DNA species. Using the analysis procedure of Southern together with previously obtained information regarding the sites of action of certain restriction endonucleases on avian sarcoma virus DNA, we have further characterized the viral DNA intermediates. Evidence is presented that, relative to the RNA genome, most of the linear species possess a direct terminal sequence redundancy equivalent to 0.5 X 10(6) +/- 0.3 X 10(6) daltons of double-stranded DNA. Some of the circular forms also possess a sequence redundancy of 0.21 X 10(6) +/- 0.03 X 10(6) daltons.", "contents": "Analysis of unintegrated avian RNA tumor virus double-stranded DNA intermediates. Previous studies by Guntaka et al. have shown that the unintegrated DNA intermediates of avian RNA tumor virus replication can be readily isolated from cultures of the quail tumor line QT-6 at 1 day after infection. The intermediates include double-stranded linear and covalently closed circular DNA species. Using the analysis procedure of Southern together with previously obtained information regarding the sites of action of certain restriction endonucleases on avian sarcoma virus DNA, we have further characterized the viral DNA intermediates. Evidence is presented that, relative to the RNA genome, most of the linear species possess a direct terminal sequence redundancy equivalent to 0.5 X 10(6) +/- 0.3 X 10(6) daltons of double-stranded DNA. Some of the circular forms also possess a sequence redundancy of 0.21 X 10(6) +/- 0.03 X 10(6) daltons."}
{"id": "PMID:215782", "title": "Specificity of cell surface virus receptors on radiation leukemia virus and radiation-induced thymic lymphomas.", "content": "We have developed a system for analysis of murine leukemic virus (MuLV) receptors on the surface of thymic lymphoma cells utilizing the fluorescence-activated cell sorter. The binding of fluoresceinated or rhodaminated MuLV to target cells showed saturation kinetics and was blocked by homologous MuLV, and bound MuLV had a polypeptide profile identical to that of input MuLV. Thymic lymphomas bound specifically the MuLV which induced them, whereas only 0.5 to 2% of normal thymocytes showed equivalent MuLV binding. Simultaneous binding of excess fluoresceinated RadLV and rhodaminated MCF-247 AKR virus to radiation leukemia virus-induced or spontaneous AKR thymic lymphomas demonstrated that even in the presence of both viruses the cells bound preferentially the inducing MuLV. Examination of the C57BL/Ka endogenous viruses showed that radiation leukemia virus-induced thymic lymphomas bind only thymotropic-leukemogenic radiation leukemia virus and not eco- or xenofibrotropic MuLV's. Thus, virus binding in this system involves only leukemogenic isolates of these retroviruses and implies a central role of this receptor-ligand interaction in the processes of leukemic transformation.", "contents": "Specificity of cell surface virus receptors on radiation leukemia virus and radiation-induced thymic lymphomas. We have developed a system for analysis of murine leukemic virus (MuLV) receptors on the surface of thymic lymphoma cells utilizing the fluorescence-activated cell sorter. The binding of fluoresceinated or rhodaminated MuLV to target cells showed saturation kinetics and was blocked by homologous MuLV, and bound MuLV had a polypeptide profile identical to that of input MuLV. Thymic lymphomas bound specifically the MuLV which induced them, whereas only 0.5 to 2% of normal thymocytes showed equivalent MuLV binding. Simultaneous binding of excess fluoresceinated RadLV and rhodaminated MCF-247 AKR virus to radiation leukemia virus-induced or spontaneous AKR thymic lymphomas demonstrated that even in the presence of both viruses the cells bound preferentially the inducing MuLV. Examination of the C57BL/Ka endogenous viruses showed that radiation leukemia virus-induced thymic lymphomas bind only thymotropic-leukemogenic radiation leukemia virus and not eco- or xenofibrotropic MuLV's. Thus, virus binding in this system involves only leukemogenic isolates of these retroviruses and implies a central role of this receptor-ligand interaction in the processes of leukemic transformation."}
{"id": "PMID:215783", "title": "Physical mapping of BK virus DNA with SacI, MboII, and AluI restriction endonucleases.", "content": "A new restriction endonuclease, SacI from Streptomyces achromogenes cleaves BK virus (strain MM) DNA into 3 fragments, whereas MboII from Moraxella bovis and AluI from Arthrobacter luteus give 22 and 30 fragments, respectively. All these specific DNA fragments were ordered and mapped on the viral genome by two methods first, by the reciprocal digestion method using uniformly 32P-labeled DNA; and second, by the partial digestion technique using the single-end 32P-labeled DNA. This study, together with those reported earlier, defined the location of 90 cleavage sites on the BK virus DNA.", "contents": "Physical mapping of BK virus DNA with SacI, MboII, and AluI restriction endonucleases. A new restriction endonuclease, SacI from Streptomyces achromogenes cleaves BK virus (strain MM) DNA into 3 fragments, whereas MboII from Moraxella bovis and AluI from Arthrobacter luteus give 22 and 30 fragments, respectively. All these specific DNA fragments were ordered and mapped on the viral genome by two methods first, by the reciprocal digestion method using uniformly 32P-labeled DNA; and second, by the partial digestion technique using the single-end 32P-labeled DNA. This study, together with those reported earlier, defined the location of 90 cleavage sites on the BK virus DNA."}
{"id": "PMID:215784", "title": "Extent of transcription of the E strand of polyoma virus DNA during the early phase of productive infection.", "content": "Early polyoma virus-specific RNA, in nuclei and cytoplasm of cells labeled with [(3)H]uridine, was analyzed by hybridization with filter-bound Hpa II fragments of polyoma DNA. About 40% of labeled cytoplasmic virus-specific RNA hybridized with Hpa II fragment 2, which represents about 40% of the region coding for E-strand mRNA's; less than 5% hybridized with fragments 1 or 3, which lie outside this region. A somewhat lower proportion (about 30%) of labeled nuclear virus-specific RNA hybridized with fragment 2, and a small but significant fraction (7 to 14%) hybridized with fragments 1 and 3. About two-thirds of the nuclear RNA which hybridized to fragment 1 was complementary to the E strand, and one-third was complementary to the L strand. Results did not vary greatly in samples labeled for periods of from 15 min to 3 h. The major species of pulse-labeled nuclear polyoma-specific RNA sedimented at 22S and thus is slightly larger than the 19S cytoplasmic mRNA. These results show that most early nuclear RNA ( approximately 75%) is transcribed from the region of the E strand, which codes for early mRNA's, and that there is probably a site at which transcription is terminated at the end of this region. However, a small amount of early nuclear RNA ( approximately 15%) is transcribed from the remainder of the E strand, perhaps by readthrough of this termination signal. In addition, there is a small amount of transcription from the L strand, whose significance is unclear. Neither the L-strand transcripts nor the nonmessenger E-strand transcripts are transported to the cytoplasm.", "contents": "Extent of transcription of the E strand of polyoma virus DNA during the early phase of productive infection. Early polyoma virus-specific RNA, in nuclei and cytoplasm of cells labeled with [(3)H]uridine, was analyzed by hybridization with filter-bound Hpa II fragments of polyoma DNA. About 40% of labeled cytoplasmic virus-specific RNA hybridized with Hpa II fragment 2, which represents about 40% of the region coding for E-strand mRNA's; less than 5% hybridized with fragments 1 or 3, which lie outside this region. A somewhat lower proportion (about 30%) of labeled nuclear virus-specific RNA hybridized with fragment 2, and a small but significant fraction (7 to 14%) hybridized with fragments 1 and 3. About two-thirds of the nuclear RNA which hybridized to fragment 1 was complementary to the E strand, and one-third was complementary to the L strand. Results did not vary greatly in samples labeled for periods of from 15 min to 3 h. The major species of pulse-labeled nuclear polyoma-specific RNA sedimented at 22S and thus is slightly larger than the 19S cytoplasmic mRNA. These results show that most early nuclear RNA ( approximately 75%) is transcribed from the region of the E strand, which codes for early mRNA's, and that there is probably a site at which transcription is terminated at the end of this region. However, a small amount of early nuclear RNA ( approximately 15%) is transcribed from the remainder of the E strand, perhaps by readthrough of this termination signal. In addition, there is a small amount of transcription from the L strand, whose significance is unclear. Neither the L-strand transcripts nor the nonmessenger E-strand transcripts are transported to the cytoplasm."}
{"id": "PMID:215785", "title": "Cell-free translation of purified virion-associated high-molecular-weight RNA synthesized in vitro by vaccinia virus.", "content": "Virion-associated high-molecular-weight (HMW) RNA synthesized in vitro by purified vaccinia virus particles has been translated in a wheat germ cell-free protein synthesizing system. Purified HMW RNA directs the synthesis of translation products which are identical to the translation products made in response to in vitro-synthesized, virion-released 8 to 12S mRNA. The translation of HMW RNA proceeds exclusively through a 5'-terminal cap-mediated initiation step. Furthermore, only one coding sequence is translated per HMW RNA molecule, and that sequence is probably located near the 5' end of the molecule. These conclusions are based on the following results. (i) Sodium dodecyl sulfate--polyacrylamide gel electrophoresis patterns of translation products synthesized in response to HMW RNA and in response to 8 to 12S mRNA were qualitatively identical. (ii) On an equal weight basis, HMW RNA was 25 to 30% as active as 8 to 12S mRNA in stimulating in vitro protein synthesis. (iii) Unmethylated HMW RNA was translated at 10% the efficiency of the methylated form of this RNA. (iv) m7pG inhibited the translation of fully methylated HMW RNA by 90%. (v) After the initiation step of translation was blocked by aurintricarboxylic acid, the rate with which amino acids were incorporated into individual polypeptides decreased in a similar manner for the translation of both HMW RNA and 8 to 12S mRNA. Virion-released 8 to 12S mRNA derived from virion-associated HMW RNA during a chase in the presence of ATP, GTP, and S-adenosylmethionine was also translated. At low RNA concentrations, the derived RNA appeared to stimulate amino acid incorporation more efficiently than the HMW RNA precursor. However, at higher concentrations of this RNA, protein synthesis was severely inhibited.", "contents": "Cell-free translation of purified virion-associated high-molecular-weight RNA synthesized in vitro by vaccinia virus. Virion-associated high-molecular-weight (HMW) RNA synthesized in vitro by purified vaccinia virus particles has been translated in a wheat germ cell-free protein synthesizing system. Purified HMW RNA directs the synthesis of translation products which are identical to the translation products made in response to in vitro-synthesized, virion-released 8 to 12S mRNA. The translation of HMW RNA proceeds exclusively through a 5'-terminal cap-mediated initiation step. Furthermore, only one coding sequence is translated per HMW RNA molecule, and that sequence is probably located near the 5' end of the molecule. These conclusions are based on the following results. (i) Sodium dodecyl sulfate--polyacrylamide gel electrophoresis patterns of translation products synthesized in response to HMW RNA and in response to 8 to 12S mRNA were qualitatively identical. (ii) On an equal weight basis, HMW RNA was 25 to 30% as active as 8 to 12S mRNA in stimulating in vitro protein synthesis. (iii) Unmethylated HMW RNA was translated at 10% the efficiency of the methylated form of this RNA. (iv) m7pG inhibited the translation of fully methylated HMW RNA by 90%. (v) After the initiation step of translation was blocked by aurintricarboxylic acid, the rate with which amino acids were incorporated into individual polypeptides decreased in a similar manner for the translation of both HMW RNA and 8 to 12S mRNA. Virion-released 8 to 12S mRNA derived from virion-associated HMW RNA during a chase in the presence of ATP, GTP, and S-adenosylmethionine was also translated. At low RNA concentrations, the derived RNA appeared to stimulate amino acid incorporation more efficiently than the HMW RNA precursor. However, at higher concentrations of this RNA, protein synthesis was severely inhibited."}
{"id": "PMID:215786", "title": "Membrane fusion as a mechanism of simian virus 40 entry into different cellular compartments.", "content": "Permissive and nonpermissive simian virus 40 (SV40)-infected cells were ultrastructurally analyzed. Viral particles were found in the cytoplasm, rough endoplasmic reticulum, nuclear envelope, lysosomes, and mitochondria. Upon entering the cell the virion obtains a tight membrane envelope. It seems to be either released from the envelope upon fusion with other membranes of the cell or aggregated into tubular membrane specializations upon fusion with other membrane-enveloped particles. Reconstructed morphological sequences and the finding of SV40 in different spaces of the cell suggest that entry of SV40 into the different compartments and eventually into the site of replication is facilitated by its capacity for being enveloped by a variety of membranes (notably the cell membrane and the nuclear membrane) and the sequential fusion and fission of these membranes.", "contents": "Membrane fusion as a mechanism of simian virus 40 entry into different cellular compartments. Permissive and nonpermissive simian virus 40 (SV40)-infected cells were ultrastructurally analyzed. Viral particles were found in the cytoplasm, rough endoplasmic reticulum, nuclear envelope, lysosomes, and mitochondria. Upon entering the cell the virion obtains a tight membrane envelope. It seems to be either released from the envelope upon fusion with other membranes of the cell or aggregated into tubular membrane specializations upon fusion with other membrane-enveloped particles. Reconstructed morphological sequences and the finding of SV40 in different spaces of the cell suggest that entry of SV40 into the different compartments and eventually into the site of replication is facilitated by its capacity for being enveloped by a variety of membranes (notably the cell membrane and the nuclear membrane) and the sequential fusion and fission of these membranes."}
{"id": "PMID:215787", "title": "Comparison of the expression of the src gene of Rous sarcoma virus in vitro and in vivo.", "content": "We have compared the polypeptide products of the src gene of several strains of Rous sarcoma virus produced by in vitro translation of heat-denatured 70S virion RNA in the nuclease-treated reticulocyte lysate with those present in chick cells transformed by these viruses. We have done this by immunoprecipitation, using sera from rabbits injected at birth with Schmidt-Ruppin Rous sarcoma virus. In vitro translation results in the synthesis of at least nine polypeptides which appear to be encoded by the src gene. These range in size from 17,000 to 60,000 daltons. The sera from tumor-bearing rabbits precipitated these polypeptides arising from the in vitro translation of RNA from Schmidt-Ruppin Rous sarcoma virus of both subgroup A and subgroup D and from one stock of Prague Rous sarcoma virus of subgroup C. In each case, all of this family of related polypeptides could be precipitated except the smallest, the 17,000-dalton polypeptide. No precipitation of analogous polypeptides resulting from the translation of RNA from other strains of Rous sarcoma virus was observed. Cells transformed by these three strains of Rous sarcoma virus contain easily detectable amounts of a polypeptide, p60src, essentially identical to the 60,000-dalton in vitro product. With one exception, they do not contain significant amounts of polypeptides analogous to the smaller in vitro products which can be precipitated by these sera. Cells transformed by one stock of Schmidt-Ruppin Rous sarcoma virus of subgroup A did contain a 39,000-dalton polypeptide, which was related, by peptide mapping, to the 60,000-dalton polypeptide and was similar in size to a precipitable in vitro product. The 60,000-dalton polypeptide present in transformed cells appeared to be phosphorylated 10 to 25 min after its synthesis, metabolically very stable, and not derived from a precursor polypeptide. All immunoprecipitates from transformed cells which contained p60src also contained an 80,000-dalton phosphoprotein. This polypeptide is unrelated to p60src, as determined by peptide mapping, and may well be a host cell polypeptide which is specifically associated with p60src.", "contents": "Comparison of the expression of the src gene of Rous sarcoma virus in vitro and in vivo. We have compared the polypeptide products of the src gene of several strains of Rous sarcoma virus produced by in vitro translation of heat-denatured 70S virion RNA in the nuclease-treated reticulocyte lysate with those present in chick cells transformed by these viruses. We have done this by immunoprecipitation, using sera from rabbits injected at birth with Schmidt-Ruppin Rous sarcoma virus. In vitro translation results in the synthesis of at least nine polypeptides which appear to be encoded by the src gene. These range in size from 17,000 to 60,000 daltons. The sera from tumor-bearing rabbits precipitated these polypeptides arising from the in vitro translation of RNA from Schmidt-Ruppin Rous sarcoma virus of both subgroup A and subgroup D and from one stock of Prague Rous sarcoma virus of subgroup C. In each case, all of this family of related polypeptides could be precipitated except the smallest, the 17,000-dalton polypeptide. No precipitation of analogous polypeptides resulting from the translation of RNA from other strains of Rous sarcoma virus was observed. Cells transformed by these three strains of Rous sarcoma virus contain easily detectable amounts of a polypeptide, p60src, essentially identical to the 60,000-dalton in vitro product. With one exception, they do not contain significant amounts of polypeptides analogous to the smaller in vitro products which can be precipitated by these sera. Cells transformed by one stock of Schmidt-Ruppin Rous sarcoma virus of subgroup A did contain a 39,000-dalton polypeptide, which was related, by peptide mapping, to the 60,000-dalton polypeptide and was similar in size to a precipitable in vitro product. The 60,000-dalton polypeptide present in transformed cells appeared to be phosphorylated 10 to 25 min after its synthesis, metabolically very stable, and not derived from a precursor polypeptide. All immunoprecipitates from transformed cells which contained p60src also contained an 80,000-dalton phosphoprotein. This polypeptide is unrelated to p60src, as determined by peptide mapping, and may well be a host cell polypeptide which is specifically associated with p60src."}
{"id": "PMID:215788", "title": "Nucleotide sequence relationships between the genomes of an endogenous and an exogenous avian tumor virus.", "content": "We have used mapping of large T1 oligonucleotides to examine the genome of Rous-associated virus-O (RAV-O), an endogenous virus of chickens, and to compare it with that of Prague strain Rous sarcoma virus, subgroup B, (Pr-RSV-B), an exogenous sarcoma virus. To extend the sensitivity of such comparisons, we have developed a system of nucleic acid hybridization and hybridization-competition combined with fingerprinting. This method allows us to estimate the relative degree of relatedness of various portions of the viral genomes. From the results of this study, we have concluded that the genomes of Pr-RSV-B and RAV-O are related in the following way. The 5'-terminal half of the genomes (corresponding to the gag and pol regions) is virtually identical, with only scattered single nucleotide differences. This region is followed by a region comprising 25 to 30% of the genome (the env region) which contains substantial nucleotide sequence differences, most or all of which are due to single base changes. The env-coding region can be further subdivided into three regions: a more variable region probably containing sequences coding for subgroup specificity, flanked by relatively common sequences on each side. To the 3' side of the env region, the RAV-O genome contains a very short sequence not found in Pr-RSV-B, whereas the Pr-RSV-B genome contains a much longer unrelated sequence. The central portion of this sequence comprises the src gene as defined by transformation-defective mutants. Particularly striking is the absence, in the RAV-O genome, of any nucleotide sequence related to the \"c region\" found very near the 3' end of all exogenous tumor viruses. Both the Pr-RSV-B and RAV-O genomes contain the identical terminally redundant sequence of 21 nucleotides near each end of the genome.", "contents": "Nucleotide sequence relationships between the genomes of an endogenous and an exogenous avian tumor virus. We have used mapping of large T1 oligonucleotides to examine the genome of Rous-associated virus-O (RAV-O), an endogenous virus of chickens, and to compare it with that of Prague strain Rous sarcoma virus, subgroup B, (Pr-RSV-B), an exogenous sarcoma virus. To extend the sensitivity of such comparisons, we have developed a system of nucleic acid hybridization and hybridization-competition combined with fingerprinting. This method allows us to estimate the relative degree of relatedness of various portions of the viral genomes. From the results of this study, we have concluded that the genomes of Pr-RSV-B and RAV-O are related in the following way. The 5'-terminal half of the genomes (corresponding to the gag and pol regions) is virtually identical, with only scattered single nucleotide differences. This region is followed by a region comprising 25 to 30% of the genome (the env region) which contains substantial nucleotide sequence differences, most or all of which are due to single base changes. The env-coding region can be further subdivided into three regions: a more variable region probably containing sequences coding for subgroup specificity, flanked by relatively common sequences on each side. To the 3' side of the env region, the RAV-O genome contains a very short sequence not found in Pr-RSV-B, whereas the Pr-RSV-B genome contains a much longer unrelated sequence. The central portion of this sequence comprises the src gene as defined by transformation-defective mutants. Particularly striking is the absence, in the RAV-O genome, of any nucleotide sequence related to the \"c region\" found very near the 3' end of all exogenous tumor viruses. Both the Pr-RSV-B and RAV-O genomes contain the identical terminally redundant sequence of 21 nucleotides near each end of the genome."}
{"id": "PMID:215789", "title": "Characterization of the amino-terminal tryptic peptide of simian virus 40 small-t and large-T antigens.", "content": "Simian virus 40 small-t and large-T antigen were synthesized in vitro and labeled with methionine donated by initiator tRNA. Tryptic peptide fingerprinting was used to identify the amino-terminal peptide of the two proteins. Similar fingerprint analysis of small-t and large-T made in vitro in the absence of acetyl coenzyme A showed that the mobility of the amino-terminal peptide was changed under these conditions and suggested that it is acetylated. These data establish that the amino-terminal methionine residue of simian virus 40 small-t and large-T results from an initiation event, not post-translational cleavage, and provides additional evidence that the amino terminus of both proteins is acetylated. The identification of the amino-terminal peptide provides a useful marker for further studies on different forms of T-antigen from cells infected with and transformed by simian virus 40 and related viruses.", "contents": "Characterization of the amino-terminal tryptic peptide of simian virus 40 small-t and large-T antigens. Simian virus 40 small-t and large-T antigen were synthesized in vitro and labeled with methionine donated by initiator tRNA. Tryptic peptide fingerprinting was used to identify the amino-terminal peptide of the two proteins. Similar fingerprint analysis of small-t and large-T made in vitro in the absence of acetyl coenzyme A showed that the mobility of the amino-terminal peptide was changed under these conditions and suggested that it is acetylated. These data establish that the amino-terminal methionine residue of simian virus 40 small-t and large-T results from an initiation event, not post-translational cleavage, and provides additional evidence that the amino terminus of both proteins is acetylated. The identification of the amino-terminal peptide provides a useful marker for further studies on different forms of T-antigen from cells infected with and transformed by simian virus 40 and related viruses."}
{"id": "PMID:215790", "title": "Structural proteins of equine infectious anemia virus.", "content": "Equine infectious anemia virus was found to be comprised of fourteen polypeptides of molecular weight ranging from 10,000 to 79,000. Eighty percent of the virion protein was accounted for by five polypeptides, including two non-glycosylated components (p29 and p13) comprising one-half of the virion protein and three glycoproteins (gp77/79, gp64, and gp40).", "contents": "Structural proteins of equine infectious anemia virus. Equine infectious anemia virus was found to be comprised of fourteen polypeptides of molecular weight ranging from 10,000 to 79,000. Eighty percent of the virion protein was accounted for by five polypeptides, including two non-glycosylated components (p29 and p13) comprising one-half of the virion protein and three glycoproteins (gp77/79, gp64, and gp40)."}
{"id": "PMID:215791", "title": "Retroperitoneal myxoid variant of malignant fibrous histiocytoma: report of a case.", "content": "A case of a retroperitoneal myxoid variant of malignant fibrous histiocytoma is reported. The chief complaints were remittent fever and a painful mass on the right flank, which were misdiagnosed as acute inflammatory disease.", "contents": "Retroperitoneal myxoid variant of malignant fibrous histiocytoma: report of a case. A case of a retroperitoneal myxoid variant of malignant fibrous histiocytoma is reported. The chief complaints were remittent fever and a painful mass on the right flank, which were misdiagnosed as acute inflammatory disease."}
{"id": "PMID:215792", "title": "Urachal signet-ring cell carcinoma, a rare variant of vesical adenocarcinoma: incidence and pathological criteria.", "content": "Of 715 cases of vesical tumors reviewed 18 adenocarcinomas were selected for further study, 5 of which fulfilled all criteria of urachal origin. Herein is reported 1 rare case of such a carcinoma of the signet-ring cell type and the morphological criteria of this variant are discussed briefly. After undergoing radical cystectomy and ureterosigmoidostomy the patient has been free of recurrent tumor or metastasis for 6 years.", "contents": "Urachal signet-ring cell carcinoma, a rare variant of vesical adenocarcinoma: incidence and pathological criteria. Of 715 cases of vesical tumors reviewed 18 adenocarcinomas were selected for further study, 5 of which fulfilled all criteria of urachal origin. Herein is reported 1 rare case of such a carcinoma of the signet-ring cell type and the morphological criteria of this variant are discussed briefly. After undergoing radical cystectomy and ureterosigmoidostomy the patient has been free of recurrent tumor or metastasis for 6 years."}
{"id": "PMID:215794", "title": "Localization of prolyl hydroxylase by the immunoperoxidase method in cardiovascular tissues of hypertensive rats.", "content": "An immunohistochemical method and light microscopy were utilized to determine localization of prolyl hydroxylase in the cardiovascular tissues of hypertensive rats. The blood vessels and renal glomerulus from these animals demonstrated an enhanced immunoreaction for prolyl hydroxylase. As the most prominent staining was observed in medial smooth muscle cells of blood vessels, these are probably the major collagen-producing cells in arteriosclerotic lesions induced by hypertension. In the glomerulus, endothelial cells and probably mesangial cells are mainly responsible for the collagen formation. An intense immunoreaction was also found in the fibroblasts which proliferated in the area of myocardial fibrosis in hypertensive rats, while there was no specific staining in myocardial cells in either hypertensive or normotensive rats.", "contents": "Localization of prolyl hydroxylase by the immunoperoxidase method in cardiovascular tissues of hypertensive rats. An immunohistochemical method and light microscopy were utilized to determine localization of prolyl hydroxylase in the cardiovascular tissues of hypertensive rats. The blood vessels and renal glomerulus from these animals demonstrated an enhanced immunoreaction for prolyl hydroxylase. As the most prominent staining was observed in medial smooth muscle cells of blood vessels, these are probably the major collagen-producing cells in arteriosclerotic lesions induced by hypertension. In the glomerulus, endothelial cells and probably mesangial cells are mainly responsible for the collagen formation. An intense immunoreaction was also found in the fibroblasts which proliferated in the area of myocardial fibrosis in hypertensive rats, while there was no specific staining in myocardial cells in either hypertensive or normotensive rats."}
{"id": "PMID:215795", "title": "Comparative controlled clinical trial of pivmecillinam and nalidixic acid in patients with acute simple urinary tract infections.", "content": "We performed a controlled double-blind clinical study with PMPC to investigate its therapeutic usefulness in acute simple cystitis in comparison with NA, with the results as follows: 1. In both treatment groups, PMPC proved to be remarkably more active (MIC) than NA against the bacterial isolates tested in vitro. 2. PMPC, administered in dosis (200 mg per day) one-tenth those of NA (2,000 mg per day), produced a greater improvement (therapeutic effects) than NA. 3. Side-effects were apparently less frequent with PMPC, as compared to NA. The results indicate a remarkable usefulness of PMPC in the treatment of acute simple cystitis.", "contents": "Comparative controlled clinical trial of pivmecillinam and nalidixic acid in patients with acute simple urinary tract infections. We performed a controlled double-blind clinical study with PMPC to investigate its therapeutic usefulness in acute simple cystitis in comparison with NA, with the results as follows: 1. In both treatment groups, PMPC proved to be remarkably more active (MIC) than NA against the bacterial isolates tested in vitro. 2. PMPC, administered in dosis (200 mg per day) one-tenth those of NA (2,000 mg per day), produced a greater improvement (therapeutic effects) than NA. 3. Side-effects were apparently less frequent with PMPC, as compared to NA. The results indicate a remarkable usefulness of PMPC in the treatment of acute simple cystitis."}
{"id": "PMID:215798", "title": "The effect of thyroxine on (Na+, K+)-ATPase from the heart and the kidney of rabbit.", "content": "The effect of thyroxine on membrane bound (Na+, K+)-ATPase isolated as a microsomal fraction from rabbit heart and kidney was investigated. In the heart, thyroxine administration produced an increased Ki value (a concentration of ouabain required for half maximal inhibition of (Na+, K+)-ATPase activity) without alteration of the specific activity of cardiac (Na+, K+)-ATPase, indicating that the digitalis sensitivity of cardiac (Na+, K+)-ATPase was decreased. On the contrary, a significant increase of the specific activity of renal (Na+, K+)-ATPase was observed without change in its digitalis sensitivity. These results suggest that (1) a decreased sensitivity of cardiac (Na+, K+)-ATPase to digitalis glycosides in thyrotoxic animals may contribute to the decrease in the inotropic and toxic effects of the digitalis glycosides in the hyperthyroid state, and that (2) there may be an organ difference in (Na+, K+)-ATPase.", "contents": "The effect of thyroxine on (Na+, K+)-ATPase from the heart and the kidney of rabbit. The effect of thyroxine on membrane bound (Na+, K+)-ATPase isolated as a microsomal fraction from rabbit heart and kidney was investigated. In the heart, thyroxine administration produced an increased Ki value (a concentration of ouabain required for half maximal inhibition of (Na+, K+)-ATPase activity) without alteration of the specific activity of cardiac (Na+, K+)-ATPase, indicating that the digitalis sensitivity of cardiac (Na+, K+)-ATPase was decreased. On the contrary, a significant increase of the specific activity of renal (Na+, K+)-ATPase was observed without change in its digitalis sensitivity. These results suggest that (1) a decreased sensitivity of cardiac (Na+, K+)-ATPase to digitalis glycosides in thyrotoxic animals may contribute to the decrease in the inotropic and toxic effects of the digitalis glycosides in the hyperthyroid state, and that (2) there may be an organ difference in (Na+, K+)-ATPase."}
{"id": "PMID:215807", "title": "Epidemiological studies on Japanese encephalitis in Kyoto City area, Japan. III. Seasonal prevalence of virus infections in several pig populations shown by virus recovery from engorged Culex tritaeniorhynchus summorosus.", "content": "When vector mosquitoes engorged by feeding on pigs are tested for virus recovery after incubation for 7 to 10 days, the results may show mosquito infection itself. Therefore, seasonal prevalence of infection in each pig population can be estimated from course of the infection rate among mosquitoes. Many mosquitoes of the main vector of Japanese encephalitis virus, Culex tritaeniorhynchus summorosus, collected by light traps everyday or every other day in some pig sheds from 1967 to 1970 were tested for virus recovery after incubation. The tests were positive during about a month period each summer, and the peak infection rate was high being over 10%. The course of the mosquito infection showed a certain pattern with one or two peaks between the initial recovery and the highest peak. From the interval of 12 to 13 days after the first recovery to the peak, cyclic infection between the pig and the mosquito may occur at the same interval.", "contents": "Epidemiological studies on Japanese encephalitis in Kyoto City area, Japan. III. Seasonal prevalence of virus infections in several pig populations shown by virus recovery from engorged Culex tritaeniorhynchus summorosus. When vector mosquitoes engorged by feeding on pigs are tested for virus recovery after incubation for 7 to 10 days, the results may show mosquito infection itself. Therefore, seasonal prevalence of infection in each pig population can be estimated from course of the infection rate among mosquitoes. Many mosquitoes of the main vector of Japanese encephalitis virus, Culex tritaeniorhynchus summorosus, collected by light traps everyday or every other day in some pig sheds from 1967 to 1970 were tested for virus recovery after incubation. The tests were positive during about a month period each summer, and the peak infection rate was high being over 10%. The course of the mosquito infection showed a certain pattern with one or two peaks between the initial recovery and the highest peak. From the interval of 12 to 13 days after the first recovery to the peak, cyclic infection between the pig and the mosquito may occur at the same interval."}
{"id": "PMID:215808", "title": "Effect of dimercaptosuccinic acid on toxicity of Habu snake (Trimeresurus flavoviridis, Hallowell) venom.", "content": "Habu venom (HV) incubated with dimercaptosuccinic acid (DMS) or thiosuccinic acid (TMA), was given subcutaneously to mice. The LD50 of HV was 19.7 mg/kg, and after treatment with TMA and DMS, it was 38.1 and 47.1 mg/kg, respectively. The logarithm concentration--mortality curve for the DMS-treated HV shifted to the right compared with the curve for crude HV. The curve for the TMA-treated HV was intermediate between these two. Decimal two mg of HV was then incubated with DMS, and such was given intramuscularly to mice. Hemorrhage and edema which occurred after administration of crude HV were markedly decreased with injection of DMS-treated HV, but the myonecrosis was not greatly affected. At 24 hr after the intramuscular dosing of 1 mg of HV into rats, lymphopenia, acute involution of lymphatic tissue, decrease in liver glycogen and lipid granules in zona fasiculata were apparent, indicating the mark of a stressor. When the DMS-treated venom was administered, the blood picture and histological findings did not differ greatly from the controls. As DMS has marked anti-HV activity, it may be used to investigate treatments for cases of Habu snake bite.", "contents": "Effect of dimercaptosuccinic acid on toxicity of Habu snake (Trimeresurus flavoviridis, Hallowell) venom. Habu venom (HV) incubated with dimercaptosuccinic acid (DMS) or thiosuccinic acid (TMA), was given subcutaneously to mice. The LD50 of HV was 19.7 mg/kg, and after treatment with TMA and DMS, it was 38.1 and 47.1 mg/kg, respectively. The logarithm concentration--mortality curve for the DMS-treated HV shifted to the right compared with the curve for crude HV. The curve for the TMA-treated HV was intermediate between these two. Decimal two mg of HV was then incubated with DMS, and such was given intramuscularly to mice. Hemorrhage and edema which occurred after administration of crude HV were markedly decreased with injection of DMS-treated HV, but the myonecrosis was not greatly affected. At 24 hr after the intramuscular dosing of 1 mg of HV into rats, lymphopenia, acute involution of lymphatic tissue, decrease in liver glycogen and lipid granules in zona fasiculata were apparent, indicating the mark of a stressor. When the DMS-treated venom was administered, the blood picture and histological findings did not differ greatly from the controls. As DMS has marked anti-HV activity, it may be used to investigate treatments for cases of Habu snake bite."}
{"id": "PMID:215809", "title": "Influences of verapamil, X-537A, A-23187 and adenosine 3',5'-cyclic monophosphate on release of 5-hydroxytryptamine from rat brain slices.", "content": "Influences of verapamil, X-537A, A-23187 and cyclic-AMP on the release of [3H]-5-HT taken up into rat brain slices, were examined. Incubation with 40 mM KCl induced tritium release which was dependent on the presence of Ca2+. Verapamil, which blocks Ca2+ influx in excitable tissues, decreased potassium-induced release of 5-HT. Tritium release induced by ionophore X-537A was not dependent on extracellular Ca2+ while that induced by A-23187 required Ca2+. Cyclic-AMP, dibutyryl cyclic-AMP and theophylline did not significantly stimulate 5-HT release either in the presence or absence of Ca2+.", "contents": "Influences of verapamil, X-537A, A-23187 and adenosine 3',5'-cyclic monophosphate on release of 5-hydroxytryptamine from rat brain slices. Influences of verapamil, X-537A, A-23187 and cyclic-AMP on the release of [3H]-5-HT taken up into rat brain slices, were examined. Incubation with 40 mM KCl induced tritium release which was dependent on the presence of Ca2+. Verapamil, which blocks Ca2+ influx in excitable tissues, decreased potassium-induced release of 5-HT. Tritium release induced by ionophore X-537A was not dependent on extracellular Ca2+ while that induced by A-23187 required Ca2+. Cyclic-AMP, dibutyryl cyclic-AMP and theophylline did not significantly stimulate 5-HT release either in the presence or absence of Ca2+."}
{"id": "PMID:215813", "title": "[Triglyceride, total cholesterol and lipoprotein fraction cholesterol levels in the blood plasma of elderly and long-lived persons in the Abkhazian SSSR].", "content": "The results of examination of 21 males and 30 females of the category of elderly and long-lived persons (81--106 years old) indicate the low content in the blood plasma of total cholesterol (173 mg/100 ml), beta-lipoprotein cholesterol (106 mg/100 ml), pre-beta-lipoprotein cholesterol (18 mg/100 ml), and triglycerides (91 mg/100 ml). The average content of these lipid complexes was lower in males than in females. The low concentration of beta- and pre-beta-lipoprotein cholesterol and the large portion of alpha-lipoprotein cholesterol content in relation to the content of total cholesterol in blood plasma are evidence of a favourable proportion of atherogenous and non-atherogenous classes of lipoproteins in blood plasma of elderly and long-lived persons, which is evidently one of the causes of the lower incidence of ischemic heart disease among them and their high longevity.", "contents": "[Triglyceride, total cholesterol and lipoprotein fraction cholesterol levels in the blood plasma of elderly and long-lived persons in the Abkhazian SSSR]. The results of examination of 21 males and 30 females of the category of elderly and long-lived persons (81--106 years old) indicate the low content in the blood plasma of total cholesterol (173 mg/100 ml), beta-lipoprotein cholesterol (106 mg/100 ml), pre-beta-lipoprotein cholesterol (18 mg/100 ml), and triglycerides (91 mg/100 ml). The average content of these lipid complexes was lower in males than in females. The low concentration of beta- and pre-beta-lipoprotein cholesterol and the large portion of alpha-lipoprotein cholesterol content in relation to the content of total cholesterol in blood plasma are evidence of a favourable proportion of atherogenous and non-atherogenous classes of lipoproteins in blood plasma of elderly and long-lived persons, which is evidently one of the causes of the lower incidence of ischemic heart disease among them and their high longevity."}
{"id": "PMID:215814", "title": "Growth assessment in abnormal children.", "content": "Growth assessments are made in children to monitor their growth with time. In children with chronic disease, these data aid in determining the effect of disease on growth and planning and evaluating therapy. Stature is the most important aspect of physical growth, but weight, body composition, skeletal maturation, and sexual development are also important. Methods for making these assessments are given. Techniques for data reduction and statistical treatment of data comparing groups of children are discussed.", "contents": "Growth assessment in abnormal children. Growth assessments are made in children to monitor their growth with time. In children with chronic disease, these data aid in determining the effect of disease on growth and planning and evaluating therapy. Stature is the most important aspect of physical growth, but weight, body composition, skeletal maturation, and sexual development are also important. Methods for making these assessments are given. Techniques for data reduction and statistical treatment of data comparing groups of children are discussed."}
{"id": "PMID:215815", "title": "[Aesthesiophysiological and neurophysiological principles of organisation of the visual system (author's transl)].", "content": "The neuronal flow of signals of the visual system and the cortical modulous characteristic are described. Possible and not yet possible correlations between neuronal activity and aesthesiophysiological experience, as well as the cortical visual projection chain and its plasticity, are discussed.", "contents": "[Aesthesiophysiological and neurophysiological principles of organisation of the visual system (author's transl)]. The neuronal flow of signals of the visual system and the cortical modulous characteristic are described. Possible and not yet possible correlations between neuronal activity and aesthesiophysiological experience, as well as the cortical visual projection chain and its plasticity, are discussed."}
{"id": "PMID:215816", "title": "[Mucoepidermoid carcinoma of the conjunctiva (author's transl)].", "content": "This is a report on a mucoepidermoid carcinoma in a 69 year old male, a rare occurence, originating clinically from the conjunctiva of the globe. The microscopic features, the pathogenesis and the histological differentiation are discussed.", "contents": "[Mucoepidermoid carcinoma of the conjunctiva (author's transl)]. This is a report on a mucoepidermoid carcinoma in a 69 year old male, a rare occurence, originating clinically from the conjunctiva of the globe. The microscopic features, the pathogenesis and the histological differentiation are discussed."}
{"id": "PMID:215817", "title": "[Rotavirus infections in children (author's transl)].", "content": "In 43 out of 90 children suffering from acute gastroenteritis Rotaviruses could be identified in stool-specimens by electronmicroscopy. Symptoms were watery diarrhoea (100%), vomiting (88%), fever (77%), dehydration (47%) and upper respiratory tract infection (21%). In 3 out of 9 patients liver involvement could be documented. In 29 children i.v.-fluid therapy for 1-2 days was necessary. Only in 1 patient severe diarrhoea persisted for 11 days.", "contents": "[Rotavirus infections in children (author's transl)]. In 43 out of 90 children suffering from acute gastroenteritis Rotaviruses could be identified in stool-specimens by electronmicroscopy. Symptoms were watery diarrhoea (100%), vomiting (88%), fever (77%), dehydration (47%) and upper respiratory tract infection (21%). In 3 out of 9 patients liver involvement could be documented. In 29 children i.v.-fluid therapy for 1-2 days was necessary. Only in 1 patient severe diarrhoea persisted for 11 days."}
{"id": "PMID:215818", "title": "[Connections between respiratory regulation and paradoxical sleep in a patient with Joubert's syndrome (author's transl)].", "content": "This study reports on eight patients whose cases have been described in literature, and two patients treated by the author, showing the typical signs of Joubert's syndrome. This disease pattern is characterised by episodic hyperpnoeas and apnoeas, retardation, muscular hypotension, opsoclonia, complete or partial agenesis of the vermiform process of cerebellum, as well as a dilated fourth ventricle. The clinical symptoms are compared with the characteristic signs of REM sleep and of cataplexy.", "contents": "[Connections between respiratory regulation and paradoxical sleep in a patient with Joubert's syndrome (author's transl)]. This study reports on eight patients whose cases have been described in literature, and two patients treated by the author, showing the typical signs of Joubert's syndrome. This disease pattern is characterised by episodic hyperpnoeas and apnoeas, retardation, muscular hypotension, opsoclonia, complete or partial agenesis of the vermiform process of cerebellum, as well as a dilated fourth ventricle. The clinical symptoms are compared with the characteristic signs of REM sleep and of cataplexy."}
{"id": "PMID:215819", "title": "Mineralocorticoids, salt balance and blood pressure after prolonged ACTH administration in juvenile hypertension.", "content": "The effect of a 5 day ACTH test (40 U/24 h) on plasma aldosterone (aldo), deoxycorticosterone (DOC), plasma renin activity (PRA) and urinary excretion of aldosterone-pH1-conjugate (pH-1-aldo) and tetrahydro-DOC (TH-DOC) was investigated in 8 normotensive children (group I), 8 patients with hypertension of unknown origin (group II), and 4 hypertensive children with dexamethasone suppressible hyperaldosteronism (DSH) (group III). Changes in blood pressure and sodium balance were studied in all groups. Under baseline conditions there was no hormonal difference between group I and II. In contrast, the children in group III had a suppressed PRA and a 1.5--2 fold elevation of aldo and DOC. Plasma DOC and urinary THDOC increased continuously 10--50 fold in all groups during the ACTH test. Aldo rose transiently 2--4 fold on the first day of ACTH and fell subsequently below baseline levels in group I and II. The children with DSH (group III), however, showed an unusual, sustained aldo stimulation with ACTH. PRA decreased significantly after ACTH in group I and II. Sodium retention aTH administration. The highest blood pressure rise was observed in group III (from 124/72 to 139/90 mm Hg). The blood pressure response to ACTH was partly sodium dependent. Although aldo and DOC and sodium retention may contribute to the ACTH induced blood pressure elevation, other factors must play a role.", "contents": "Mineralocorticoids, salt balance and blood pressure after prolonged ACTH administration in juvenile hypertension. The effect of a 5 day ACTH test (40 U/24 h) on plasma aldosterone (aldo), deoxycorticosterone (DOC), plasma renin activity (PRA) and urinary excretion of aldosterone-pH1-conjugate (pH-1-aldo) and tetrahydro-DOC (TH-DOC) was investigated in 8 normotensive children (group I), 8 patients with hypertension of unknown origin (group II), and 4 hypertensive children with dexamethasone suppressible hyperaldosteronism (DSH) (group III). Changes in blood pressure and sodium balance were studied in all groups. Under baseline conditions there was no hormonal difference between group I and II. In contrast, the children in group III had a suppressed PRA and a 1.5--2 fold elevation of aldo and DOC. Plasma DOC and urinary THDOC increased continuously 10--50 fold in all groups during the ACTH test. Aldo rose transiently 2--4 fold on the first day of ACTH and fell subsequently below baseline levels in group I and II. The children with DSH (group III), however, showed an unusual, sustained aldo stimulation with ACTH. PRA decreased significantly after ACTH in group I and II. Sodium retention aTH administration. The highest blood pressure rise was observed in group III (from 124/72 to 139/90 mm Hg). The blood pressure response to ACTH was partly sodium dependent. Although aldo and DOC and sodium retention may contribute to the ACTH induced blood pressure elevation, other factors must play a role."}
{"id": "PMID:215820", "title": "The effect of chronic ACTH treatment on blood pressure and urinary excretion of steroids in the rat.", "content": "The effects of subcutaneous injections of synthetic ACTH during 14 subsequent days has been studied in the rat. ACTH caused a loss in body weight which was related to a negative water balance. Blood pressure rose rapidly and reached values higher than 180 mm Hg in all rats after 10 days of ACTH administration. During this period, urinary excretion of corticosterone and 18-hydroxy-deoxycorticosterone (18-OH-DOC) was increased more than ten times, while aldosterone excretion was increased only during the first two days. After withdrawal of ACTH, excretion of steroids normalized, or in some cases was even suppressed and water balance and body weight gain returned to normal values. However, blood pressure remained slightly higher than in controls after ten days. The effects of ACTH on water balance and blood pressure resemble those of corticosterone in the rat. The rapidly induced and sustained changes in blood pressure by ACTH administration suggest that this may be an useful model of experimental hypertension.", "contents": "The effect of chronic ACTH treatment on blood pressure and urinary excretion of steroids in the rat. The effects of subcutaneous injections of synthetic ACTH during 14 subsequent days has been studied in the rat. ACTH caused a loss in body weight which was related to a negative water balance. Blood pressure rose rapidly and reached values higher than 180 mm Hg in all rats after 10 days of ACTH administration. During this period, urinary excretion of corticosterone and 18-hydroxy-deoxycorticosterone (18-OH-DOC) was increased more than ten times, while aldosterone excretion was increased only during the first two days. After withdrawal of ACTH, excretion of steroids normalized, or in some cases was even suppressed and water balance and body weight gain returned to normal values. However, blood pressure remained slightly higher than in controls after ten days. The effects of ACTH on water balance and blood pressure resemble those of corticosterone in the rat. The rapidly induced and sustained changes in blood pressure by ACTH administration suggest that this may be an useful model of experimental hypertension."}
{"id": "PMID:215821", "title": "Inhibition of the renin-angiotensin-system in Brattleboro rats with hereditary hypothalamic diabetes insipidus.", "content": "Brattleboro rats homozygous for hypothalamic hereditary diabetes insipidus (DI rats) were used to investigate the following questions: a) Do exogenous and endogenous angiotensin II (AII) have an antidiuretic effect in diabetes insipidus? b) Does AII mediate the antidiuresis induced by furosemide? The following results were obtained: 1. AII (5 mg/kg s.c. in oil) and furosemide (50 mg/kg i.p.) decreased urine flow and increased urinary sodium excretion. Furosemide led to a two-fold increase of AII plasma concentrations and a decrease of plasma sodium levels. 2. SQ 14 225 (2 x 2.5 mg/kg p.o.), an angiotensin I-converting enzyme inhibitor, led to an increase of urine flow and to a slightly elevated urinary sodium excretion. 3. When the formation of AII was blocked by SQ 14 225 (2 x 2.5 mg/kg p.o.), AII plasma concentrations were 2.5-fold decreased, but furosemide still reduced urine flow. We conclude that plasma AII might have an antidiuretic action in DI rats. However, AII does not mediate the antidiuresis induced by furosemide.", "contents": "Inhibition of the renin-angiotensin-system in Brattleboro rats with hereditary hypothalamic diabetes insipidus. Brattleboro rats homozygous for hypothalamic hereditary diabetes insipidus (DI rats) were used to investigate the following questions: a) Do exogenous and endogenous angiotensin II (AII) have an antidiuretic effect in diabetes insipidus? b) Does AII mediate the antidiuresis induced by furosemide? The following results were obtained: 1. AII (5 mg/kg s.c. in oil) and furosemide (50 mg/kg i.p.) decreased urine flow and increased urinary sodium excretion. Furosemide led to a two-fold increase of AII plasma concentrations and a decrease of plasma sodium levels. 2. SQ 14 225 (2 x 2.5 mg/kg p.o.), an angiotensin I-converting enzyme inhibitor, led to an increase of urine flow and to a slightly elevated urinary sodium excretion. 3. When the formation of AII was blocked by SQ 14 225 (2 x 2.5 mg/kg p.o.), AII plasma concentrations were 2.5-fold decreased, but furosemide still reduced urine flow. We conclude that plasma AII might have an antidiuretic action in DI rats. However, AII does not mediate the antidiuresis induced by furosemide."}
{"id": "PMID:215822", "title": "Influence of clofibrate on blood viscosity in primary hyperlipoproteinemia.", "content": "In patients with primary hyperlipoproteinemia (23 patients type II a and II b, 13 patients type IV), changes in lipoprotein concentrations (lipid fraction), fibrinogen concentrations, in kinematic serum and plasma viscosity (determined by means of a capillary viscosimeter) and changes in relative apparent viscosity at shear rate 46 s-1 and 115 s-1 (determined by means of a plate-cone-viscosimeter) were measured before and after a clofibrate therapy (2 X 1 g/day) lasting for 7 to 9 weeks. Serum and plasma viscosity was lowered significantly in both types II and IV. The apparent viscosity decreased at shear rate 46 s-1 in type IV, whereas it remained unchanged in type II. Moreover, there exists a qualitative correlation between changes in serum viscosity and changes in lipoprotein concentration. Fibrinogen concentration remained unaltered.", "contents": "Influence of clofibrate on blood viscosity in primary hyperlipoproteinemia. In patients with primary hyperlipoproteinemia (23 patients type II a and II b, 13 patients type IV), changes in lipoprotein concentrations (lipid fraction), fibrinogen concentrations, in kinematic serum and plasma viscosity (determined by means of a capillary viscosimeter) and changes in relative apparent viscosity at shear rate 46 s-1 and 115 s-1 (determined by means of a plate-cone-viscosimeter) were measured before and after a clofibrate therapy (2 X 1 g/day) lasting for 7 to 9 weeks. Serum and plasma viscosity was lowered significantly in both types II and IV. The apparent viscosity decreased at shear rate 46 s-1 in type IV, whereas it remained unchanged in type II. Moreover, there exists a qualitative correlation between changes in serum viscosity and changes in lipoprotein concentration. Fibrinogen concentration remained unaltered."}
{"id": "PMID:215834", "title": "Collagen turnover and the growth state in 3T6 fibroblast cultures.", "content": "The metabolic turnover of collagen in 3T6 fibroblast cultures was studied at various stages of growth by compartmental analysis of hydroxyproline content and of the conversion of radioactive proline to hydroxyproline. Quantitative and radioactive hydroxyproline measurements were directly parallel, although the latter method was more sensitive in demonstrating collagen synthesis in all phases of growth. Hydroxyproline formation as an index of collagen synthesis was abruptly accelerated at the time of confluence, and was well maintained at the new rate despite a gradual decline in the rate of general protein synthesis. Ethanol fractionation of growth medium proved superior to perchloric acid extraction in providing a pool of soluble hydroxyproline clearly derived from collagen degradation. Breakdown products were released at a constant rate per cell in all growth phases and accumulated to high levels in continuous culture. The fractional rate of collagen breakdown (percentage of hydroxyproline radioactivity) was highest in early logarithmic growth. Its gradual decline as cultures aged reflected the increased hydroxyproline content and improved stability of collagen under these conditions.", "contents": "Collagen turnover and the growth state in 3T6 fibroblast cultures. The metabolic turnover of collagen in 3T6 fibroblast cultures was studied at various stages of growth by compartmental analysis of hydroxyproline content and of the conversion of radioactive proline to hydroxyproline. Quantitative and radioactive hydroxyproline measurements were directly parallel, although the latter method was more sensitive in demonstrating collagen synthesis in all phases of growth. Hydroxyproline formation as an index of collagen synthesis was abruptly accelerated at the time of confluence, and was well maintained at the new rate despite a gradual decline in the rate of general protein synthesis. Ethanol fractionation of growth medium proved superior to perchloric acid extraction in providing a pool of soluble hydroxyproline clearly derived from collagen degradation. Breakdown products were released at a constant rate per cell in all growth phases and accumulated to high levels in continuous culture. The fractional rate of collagen breakdown (percentage of hydroxyproline radioactivity) was highest in early logarithmic growth. Its gradual decline as cultures aged reflected the increased hydroxyproline content and improved stability of collagen under these conditions."}
{"id": "PMID:215835", "title": "Cell surface glycosyltransferases--do they exist?", "content": "The presence of glycosyltransferases on surfaces of mammalian cells has been reported by many investigators and a biological role for these enzymes in cell adhesion and cell recognition has been postulated. Critical analysis, however, showed 2 major complications regarding the assay for cell surface glycosyltransferases: 1) hydrolysis of the nucleotide sugar by cell surface enzymes and subsequent intracellular use of the free sugar and 2) loss of cell integrity if trypsinized or EDTA-treated cells were used in suspension assays. We have assayed intact, viable cells in monolayer for cell surface glycosyltransferases using conditions under which intracellular utilization of free sugars generated by hydrolysis of the nucleotide sugar was prevented. Our data demonstrate that the presence of galactosyltransferases on the surface of a variety of cells, including established (normal and virally transformed) as well as nonestablished cells, is unlikely. No evidence for the existence of cell surface fucosyl- and sialytransferases could be obtained, but our data do not exclude the possibility that low levels of these enzymes are present.", "contents": "Cell surface glycosyltransferases--do they exist? The presence of glycosyltransferases on surfaces of mammalian cells has been reported by many investigators and a biological role for these enzymes in cell adhesion and cell recognition has been postulated. Critical analysis, however, showed 2 major complications regarding the assay for cell surface glycosyltransferases: 1) hydrolysis of the nucleotide sugar by cell surface enzymes and subsequent intracellular use of the free sugar and 2) loss of cell integrity if trypsinized or EDTA-treated cells were used in suspension assays. We have assayed intact, viable cells in monolayer for cell surface glycosyltransferases using conditions under which intracellular utilization of free sugars generated by hydrolysis of the nucleotide sugar was prevented. Our data demonstrate that the presence of galactosyltransferases on the surface of a variety of cells, including established (normal and virally transformed) as well as nonestablished cells, is unlikely. No evidence for the existence of cell surface fucosyl- and sialytransferases could be obtained, but our data do not exclude the possibility that low levels of these enzymes are present."}
{"id": "PMID:215836", "title": "Gycoprotein and protein precursors to plasma membranes in vesicular stomatitis virus infected HeLa cells.", "content": "Vesicular stomatitis virus is known to mature at HeLa cell plasma membranes. To study the process, cells, infected with vesicular stomatitis virus, were fractionated after short term labeling studies (1 min pulse, 1 min chase) to determine the assembly kinetics of G protein and M protein into plasma membranes. Newly synthesized M protein was found released in the supernatant from which free polysomes were sedimented during sucrose gradient analysis of these polysomes. If this M protein is particle bound, it must have a density of less than 1.08 g/ml. About 40% of this M protein so labeled was not sedimentable at 165,000 X g for 16 h. This newly synthesized M protein had not yet assembled into plasma membrane and thus must represent an internal pool. This and previous studies show that it has a subsequent transit time to the plasma membrane of about 2 min. Once associated with plasma membranes, M protein decayed in an approximately logarithmic fashion indicating that newly synthesized M randomly mixes (and turns over) with preexisting M protein. G protein was particle bound in a 1 min pulse, 1 min chase, and was never found released in a soluble form. At the later time when fucose is added to G protein, the oligosaccharide moiety is near to complete, and on completion is about 2,000 in molecular weight. Evidence is presented showing that fucose is probably attached to the N-acetylglucosamine of the protein carbohydrate linkage. G protein to which fucose had just been added was located internally on a membranous fraction of density 1.14 g/ml in sucrose; its subsequent transit time from this pool (which in uninfected cells is between 1--2% of the total cell fucosyl glycoprotein) was about 15 min. Because their densities were different and their transit times were different, internal newly synthesized M and fucosyl G protein which assemble into plasma membranes were not on the same internal membranous component. Association of M protein with the plasma membranes may thus occur from a nonsedimentable soluble cytoplasmic pool by a process of direct adsorption.", "contents": "Gycoprotein and protein precursors to plasma membranes in vesicular stomatitis virus infected HeLa cells. Vesicular stomatitis virus is known to mature at HeLa cell plasma membranes. To study the process, cells, infected with vesicular stomatitis virus, were fractionated after short term labeling studies (1 min pulse, 1 min chase) to determine the assembly kinetics of G protein and M protein into plasma membranes. Newly synthesized M protein was found released in the supernatant from which free polysomes were sedimented during sucrose gradient analysis of these polysomes. If this M protein is particle bound, it must have a density of less than 1.08 g/ml. About 40% of this M protein so labeled was not sedimentable at 165,000 X g for 16 h. This newly synthesized M protein had not yet assembled into plasma membrane and thus must represent an internal pool. This and previous studies show that it has a subsequent transit time to the plasma membrane of about 2 min. Once associated with plasma membranes, M protein decayed in an approximately logarithmic fashion indicating that newly synthesized M randomly mixes (and turns over) with preexisting M protein. G protein was particle bound in a 1 min pulse, 1 min chase, and was never found released in a soluble form. At the later time when fucose is added to G protein, the oligosaccharide moiety is near to complete, and on completion is about 2,000 in molecular weight. Evidence is presented showing that fucose is probably attached to the N-acetylglucosamine of the protein carbohydrate linkage. G protein to which fucose had just been added was located internally on a membranous fraction of density 1.14 g/ml in sucrose; its subsequent transit time from this pool (which in uninfected cells is between 1--2% of the total cell fucosyl glycoprotein) was about 15 min. Because their densities were different and their transit times were different, internal newly synthesized M and fucosyl G protein which assemble into plasma membranes were not on the same internal membranous component. Association of M protein with the plasma membranes may thus occur from a nonsedimentable soluble cytoplasmic pool by a process of direct adsorption."}
{"id": "PMID:215837", "title": "Erythrocyte membrane alterations in Huntington disease: effects of gamma-aminobutyric acid.", "content": "The interaction of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) with erythrocyte membranes from patients with Huntington disease and normal controls has been studied by electron spin resonance. GABA affects the physical state of erythrocyte membrane proteins in control and Huntington disease differently. In addition, after exposure of spin-labeled Huntington disease erythrocyte membranes to 0.1 mM GABA, the relevant electron spin resonance parameters reflecting the physical state of membrane proteins are indistinguishable from those of untreated control membranes. These findings support the concept that this disease is associated with a generalized membrane defect.", "contents": "Erythrocyte membrane alterations in Huntington disease: effects of gamma-aminobutyric acid. The interaction of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) with erythrocyte membranes from patients with Huntington disease and normal controls has been studied by electron spin resonance. GABA affects the physical state of erythrocyte membrane proteins in control and Huntington disease differently. In addition, after exposure of spin-labeled Huntington disease erythrocyte membranes to 0.1 mM GABA, the relevant electron spin resonance parameters reflecting the physical state of membrane proteins are indistinguishable from those of untreated control membranes. These findings support the concept that this disease is associated with a generalized membrane defect."}
{"id": "PMID:215838", "title": "Use of photoaffinity nucleotide analogs to determine the mechanism of ATP regulation of a membrane-bound, cAMP-activated protein kinase.", "content": "Using a radioactively tagged, photoaffinity analog of cAMP, 8-azidoadenosine-3',5'-cyclic monophosphate (8-N3 cAMP) and [gamma32P]ATP, the membrane-binding properties of both the regulatory and catalytic subunits of the cAMP-activated protein kinase of human erythrocyte membranes were investigated. [32P]8-N3 cAMP was used to locate and quantify regulatory subunits. Increased phosphorylation of specific membrane proteins by [gamma32P]ATP was used to determine the presence of the catalytic subunit. The data support a mechanism which operates through a tight membrane-bound regulatory subunit and a catalytic subunit that is released from the membrane when cAMP is present and the Mg.ATP concentration is below approximately 10 micrometer. The catalytic subunit is not required for the Mg.ATP inhibition of 8-N3 cAMP binding. Experiments with a photoaffinity analog of ATP, 8-azidoadenosine triphosphate (8-N3ATP), support the hypothesis that ATP hydrolysis and phosphorylation are not involved in the regulation. The data indicate that the regulatory subunit contains an ATP regulatory site which inhibits 8-N3 cAMP binding and the release of the catalytic subunit. These results indicate that the membrane-bound type I enzyme (type IM) differs significantly from the soluble (type IS) enzyme studied on other tissues. These enzymes are compartmentalized by being in different cellular locations and are regulated differently by Mg.ATP.", "contents": "Use of photoaffinity nucleotide analogs to determine the mechanism of ATP regulation of a membrane-bound, cAMP-activated protein kinase. Using a radioactively tagged, photoaffinity analog of cAMP, 8-azidoadenosine-3',5'-cyclic monophosphate (8-N3 cAMP) and [gamma32P]ATP, the membrane-binding properties of both the regulatory and catalytic subunits of the cAMP-activated protein kinase of human erythrocyte membranes were investigated. [32P]8-N3 cAMP was used to locate and quantify regulatory subunits. Increased phosphorylation of specific membrane proteins by [gamma32P]ATP was used to determine the presence of the catalytic subunit. The data support a mechanism which operates through a tight membrane-bound regulatory subunit and a catalytic subunit that is released from the membrane when cAMP is present and the Mg.ATP concentration is below approximately 10 micrometer. The catalytic subunit is not required for the Mg.ATP inhibition of 8-N3 cAMP binding. Experiments with a photoaffinity analog of ATP, 8-azidoadenosine triphosphate (8-N3ATP), support the hypothesis that ATP hydrolysis and phosphorylation are not involved in the regulation. The data indicate that the regulatory subunit contains an ATP regulatory site which inhibits 8-N3 cAMP binding and the release of the catalytic subunit. These results indicate that the membrane-bound type I enzyme (type IM) differs significantly from the soluble (type IS) enzyme studied on other tissues. These enzymes are compartmentalized by being in different cellular locations and are regulated differently by Mg.ATP."}
{"id": "PMID:215839", "title": "Glucocorticoid-mediated alteration in growth factor binding and action: analysis of the binding change.", "content": "The addition of the glucocorticoid analog dexamethasone (DX) to serum-free cultures of human fibroblasts caused a twofold enhancement of the mitogenic response to epidermal growth factor (EGF), although DX by itself was not mitogenic. A basis for this effect was suggested by studies showing that DX also increased the cellular binding of 125I-EGF. DX increased the ability of the cells to bind 125I-EGF only at low physiological concentrations of this polypeptide. Thus, data from 125 I-EGF binding to cells incubated without DX produced a linear Scatchard plot, whereas the data from 125I-EGF binding to DX-treated cells led to an upwardly curvilinear Scatchard plot. Measurements of 125I-EGF association with the cell surface and cytoplasm indicated that this binding change involved an alteration of cell surface EGF receptors. The binding change appeared not to involve negatively cooperative interactions between EGF receptors, nor a change in the number of receptors. The binding alteration could be explained by a model in which DX converted 25--30% of the cell surface EGF receptors to a form having a fourfold increased affinity.", "contents": "Glucocorticoid-mediated alteration in growth factor binding and action: analysis of the binding change. The addition of the glucocorticoid analog dexamethasone (DX) to serum-free cultures of human fibroblasts caused a twofold enhancement of the mitogenic response to epidermal growth factor (EGF), although DX by itself was not mitogenic. A basis for this effect was suggested by studies showing that DX also increased the cellular binding of 125I-EGF. DX increased the ability of the cells to bind 125I-EGF only at low physiological concentrations of this polypeptide. Thus, data from 125 I-EGF binding to cells incubated without DX produced a linear Scatchard plot, whereas the data from 125I-EGF binding to DX-treated cells led to an upwardly curvilinear Scatchard plot. Measurements of 125I-EGF association with the cell surface and cytoplasm indicated that this binding change involved an alteration of cell surface EGF receptors. The binding change appeared not to involve negatively cooperative interactions between EGF receptors, nor a change in the number of receptors. The binding alteration could be explained by a model in which DX converted 25--30% of the cell surface EGF receptors to a form having a fourfold increased affinity."}
{"id": "PMID:215840", "title": "REM sleep time and digit span impairment in alcoholics.", "content": "In a group of 20 abstinent alcoholics, the amount of REM sleep was correlated with the degree of Digit Span scatter from the modified verbal mean of the WAIS. The Digits Backward component was more strongly related to REM time than was the Digits Forward component, suggesting an association between reduced REM sleep time and short-term memory impairment.", "contents": "REM sleep time and digit span impairment in alcoholics. In a group of 20 abstinent alcoholics, the amount of REM sleep was correlated with the degree of Digit Span scatter from the modified verbal mean of the WAIS. The Digits Backward component was more strongly related to REM time than was the Digits Forward component, suggesting an association between reduced REM sleep time and short-term memory impairment."}
{"id": "PMID:215841", "title": "The relationship of wives' treatment to the drinking status of alcoholics.", "content": "When an alcoholic's wife is active in Al-Anon, participates in her husband's inpatient treatment or postreatment counseling or receives several types of treatment, her husband is more likely to be abstinent.", "contents": "The relationship of wives' treatment to the drinking status of alcoholics. When an alcoholic's wife is active in Al-Anon, participates in her husband's inpatient treatment or postreatment counseling or receives several types of treatment, her husband is more likely to be abstinent."}
{"id": "PMID:215842", "title": "Breast carcinoma associated with Klinefelter syndrome: a case report.", "content": "Klinefelter syndrome increases the risk of developing breast cancer to approximately 1/5 that of women and 20 times that of normal men. A case report and the patient's response to hormone manipulation for metastatic disease is described.", "contents": "Breast carcinoma associated with Klinefelter syndrome: a case report. Klinefelter syndrome increases the risk of developing breast cancer to approximately 1/5 that of women and 20 times that of normal men. A case report and the patient's response to hormone manipulation for metastatic disease is described."}
{"id": "PMID:215843", "title": "Malignant fibrous histiocytoma: report of five cases and a review of the literature.", "content": "Five cases of malignant fibrous histiocytoma are presented and the relevant literature is reviewed. All the patients had locally extensive tumor or eventual recurrent or metastatic disease. Determining malignancy by histologic criteria is difficult. Therefore, histologic, gross, and clinical behavior of the tumor is important. Though the role of radiation therapy and chemotherapy is not yet established, it appears that at least wide \"cancer resection,\" if possible, is the treatment of choice. The unusually high incidence of nonresectable, recurrent, or metastatic disease in retroperitoneal histiocytomas raises the question as to whether all three modalities of therapy should be used in the treatment of tumors at this particular site.", "contents": "Malignant fibrous histiocytoma: report of five cases and a review of the literature. Five cases of malignant fibrous histiocytoma are presented and the relevant literature is reviewed. All the patients had locally extensive tumor or eventual recurrent or metastatic disease. Determining malignancy by histologic criteria is difficult. Therefore, histologic, gross, and clinical behavior of the tumor is important. Though the role of radiation therapy and chemotherapy is not yet established, it appears that at least wide \"cancer resection,\" if possible, is the treatment of choice. The unusually high incidence of nonresectable, recurrent, or metastatic disease in retroperitoneal histiocytomas raises the question as to whether all three modalities of therapy should be used in the treatment of tumors at this particular site."}
{"id": "PMID:215844", "title": "Epstein-Barr virus (EBV) antibody in patients treated by radical radiotherapy for head and neck cancer.", "content": "Antibody against Epstein Barr Viral capsid (EBV-VCA) was measured in 65 patients with primary head and neck cancer referred for radical radiotherapy. Sixty-three percent had locally advanced cancer and 37% had early disease. Forty-eight percent had detectable antibody in their sera. Thirty-three percent had elevated titers (above 1:20 dilution). Only 19% of cases with early cancer had increased titers. Almost 50% of those with locally advanced cancer or recurrence following treatment had titers above 1:20. A rise in titer within six months following radiotherapy was associated with a significant incidence of recurrence. There was no correlation between delayed hypersensitivity skin reaction to 2--4 dinitrochlorobenzene (DNCB) and titer values. EBV-VCA may be an additional parameter which can be used to determine host defenses in patients with malignancies.", "contents": "Epstein-Barr virus (EBV) antibody in patients treated by radical radiotherapy for head and neck cancer. Antibody against Epstein Barr Viral capsid (EBV-VCA) was measured in 65 patients with primary head and neck cancer referred for radical radiotherapy. Sixty-three percent had locally advanced cancer and 37% had early disease. Forty-eight percent had detectable antibody in their sera. Thirty-three percent had elevated titers (above 1:20 dilution). Only 19% of cases with early cancer had increased titers. Almost 50% of those with locally advanced cancer or recurrence following treatment had titers above 1:20. A rise in titer within six months following radiotherapy was associated with a significant incidence of recurrence. There was no correlation between delayed hypersensitivity skin reaction to 2--4 dinitrochlorobenzene (DNCB) and titer values. EBV-VCA may be an additional parameter which can be used to determine host defenses in patients with malignancies."}
{"id": "PMID:215845", "title": "Pancreas cancer -- duct cell adenocarcinoma: survival in relation to site, size, stage and type of therapy.", "content": "The records of 508 patients with cancer of the pancreas admitted to Memorial Hospital in New York from 1949 through 1972 were examined. Ten distinctive morphological types were delineated and the pathological features and response to various modes of therapy of the most common type -- duct adenocarcinoma -- were studied in 380 patients. Median survival was related to: the site of the cancer -- it was longer with tumors of the head than those of the body or tail; the size of the tumor -- cancers smaller than 3 cm were associated with over twice the survival of those with large tumors; the stage -- stage I patients had over twice the survival of those of stages II and III; and the type of therapy employed. Actuarial survival rate at one year was: with no specific therapy, 0%; with chemotherapy, 1%; after palliative by-pass surgery, 3%; following radiation therapy, 9%; and after all types of \"surative\" surgery, 21%. The only survivors at five years were in the \"curative\" surgery group, but these represented only 1% of all patients. Revolutionary changes in diagnosis and therapy will have to occur if significant increase in survival rate is to be achieved.", "contents": "Pancreas cancer -- duct cell adenocarcinoma: survival in relation to site, size, stage and type of therapy. The records of 508 patients with cancer of the pancreas admitted to Memorial Hospital in New York from 1949 through 1972 were examined. Ten distinctive morphological types were delineated and the pathological features and response to various modes of therapy of the most common type -- duct adenocarcinoma -- were studied in 380 patients. Median survival was related to: the site of the cancer -- it was longer with tumors of the head than those of the body or tail; the size of the tumor -- cancers smaller than 3 cm were associated with over twice the survival of those with large tumors; the stage -- stage I patients had over twice the survival of those of stages II and III; and the type of therapy employed. Actuarial survival rate at one year was: with no specific therapy, 0%; with chemotherapy, 1%; after palliative by-pass surgery, 3%; following radiation therapy, 9%; and after all types of \"surative\" surgery, 21%. The only survivors at five years were in the \"curative\" surgery group, but these represented only 1% of all patients. Revolutionary changes in diagnosis and therapy will have to occur if significant increase in survival rate is to be achieved."}
{"id": "PMID:215846", "title": "Sequential and adjuvant chemotherapy for malignant astrocytoma of the brain.", "content": "Twenty-nine patients with grade III or IV astrocytomas were treated with 1,3 bis(2-chloroethyl)-1-nitrosourea (BCNU), 75--100 mg/M2 intravenously (IV) for two consecutive days every four to six weeks, in an effort to improve the quality and length of their survival following surgical resection. Twenty-one of these patients received adjunctive chemotherapy as soon as they recovered from surgery and 18 received concomitant adjunctive radiation therapy as well. Eight patients were treated with radiation therapy after surgery, and BCNU was not added until evidence of tumor growth appeared. BCNU was discontinued and the epipodophyllotoxin, VM-26, was given at a dose of 100 mg/M2 IV weekly when further tumor growth occurred. Patients receiving adjuvant chemotherapy had a shorter mean and median survival than patients receiving BCNU when progression appeared following radiation therapy. Six patients with progressive disease following surgical resection and radiation therapy for grade II astrocytoma were treated with BCNU. Improvement or stabilization of neurologic symptoms occurred in four of these patients. This trial of lower-dose BCNU therapy produced survival rates similar to higher-dose studies and permitted fewer physician visits by the patient.", "contents": "Sequential and adjuvant chemotherapy for malignant astrocytoma of the brain. Twenty-nine patients with grade III or IV astrocytomas were treated with 1,3 bis(2-chloroethyl)-1-nitrosourea (BCNU), 75--100 mg/M2 intravenously (IV) for two consecutive days every four to six weeks, in an effort to improve the quality and length of their survival following surgical resection. Twenty-one of these patients received adjunctive chemotherapy as soon as they recovered from surgery and 18 received concomitant adjunctive radiation therapy as well. Eight patients were treated with radiation therapy after surgery, and BCNU was not added until evidence of tumor growth appeared. BCNU was discontinued and the epipodophyllotoxin, VM-26, was given at a dose of 100 mg/M2 IV weekly when further tumor growth occurred. Patients receiving adjuvant chemotherapy had a shorter mean and median survival than patients receiving BCNU when progression appeared following radiation therapy. Six patients with progressive disease following surgical resection and radiation therapy for grade II astrocytoma were treated with BCNU. Improvement or stabilization of neurologic symptoms occurred in four of these patients. This trial of lower-dose BCNU therapy produced survival rates similar to higher-dose studies and permitted fewer physician visits by the patient."}
{"id": "PMID:215847", "title": "Small cell undifferentiated bronchogenic carcinoma: current status with emphasis upon the role of chemotherapy.", "content": "Current opinions concerning tumor biology and clinical characteristics of small cell undifferentiated bronchogenic carcinoma are reviewed. Special emphasis is placed upon chemotherapy for this lung cancer subtype and presently achievable response rates and survival times are presented. A series of 16 patients with small cell undifferentiated bronchogenic carcinoma is also presented. All patients were given cyclophosphamide, methotrexate, vincristine, and procarbazine as treatment for this neoplasm. Sixty-eight percent of patients responded and the survival time in partial responders was 33.4+ weeks as compared to 13.7 weeks with nonresponders. These data correlate well with the previous data of Alberto et al [Alberto P, Brunner KW, Martz G, Obrect JP: Cancer 38:2208--2216, 1976], who investigated the same agents for this tumor, but at higher dosages.", "contents": "Small cell undifferentiated bronchogenic carcinoma: current status with emphasis upon the role of chemotherapy. Current opinions concerning tumor biology and clinical characteristics of small cell undifferentiated bronchogenic carcinoma are reviewed. Special emphasis is placed upon chemotherapy for this lung cancer subtype and presently achievable response rates and survival times are presented. A series of 16 patients with small cell undifferentiated bronchogenic carcinoma is also presented. All patients were given cyclophosphamide, methotrexate, vincristine, and procarbazine as treatment for this neoplasm. Sixty-eight percent of patients responded and the survival time in partial responders was 33.4+ weeks as compared to 13.7 weeks with nonresponders. These data correlate well with the previous data of Alberto et al [Alberto P, Brunner KW, Martz G, Obrect JP: Cancer 38:2208--2216, 1976], who investigated the same agents for this tumor, but at higher dosages."}
{"id": "PMID:215849", "title": "Pericardial reconstruction of the membranous trachea after resection of adenoid cystic carcinoma (cylindroma).", "content": "An intraluminal adenoid cystic carcinoma (cylindroma) in the patient reported herein involved just the membranous portion of the distal region of the trachea and extended caudally to include the carina and the membranous portions of both main-stem bronchi--a total linear involvement of 6 cm. The tumor occluded 90% of the airway in its greatest extension. Conservative resection of this extensive tumor was successfully performed by membranous tracheal reconstruction with a pedicled autogenous pericardial patch graft.", "contents": "Pericardial reconstruction of the membranous trachea after resection of adenoid cystic carcinoma (cylindroma). An intraluminal adenoid cystic carcinoma (cylindroma) in the patient reported herein involved just the membranous portion of the distal region of the trachea and extended caudally to include the carina and the membranous portions of both main-stem bronchi--a total linear involvement of 6 cm. The tumor occluded 90% of the airway in its greatest extension. Conservative resection of this extensive tumor was successfully performed by membranous tracheal reconstruction with a pedicled autogenous pericardial patch graft."}
{"id": "PMID:215850", "title": "Congenital absence of the portal vein.", "content": "A 4 1/2-year-old girl is described in whom the portal vein is absent and the venous return from the gastrointestinal tract, spleen, and pancreas is through the left renal vein into the inferior vena cava. She had a hepatoblastoma, which was treated surgically by right hepatic lobectomy. Regeneration occurred in the remaining left lobe within 3 months after surgery. This is the second such case documented in the literature.", "contents": "Congenital absence of the portal vein. A 4 1/2-year-old girl is described in whom the portal vein is absent and the venous return from the gastrointestinal tract, spleen, and pancreas is through the left renal vein into the inferior vena cava. She had a hepatoblastoma, which was treated surgically by right hepatic lobectomy. Regeneration occurred in the remaining left lobe within 3 months after surgery. This is the second such case documented in the literature."}
{"id": "PMID:215851", "title": "Anomalous vitamin E effects in mitochondrial oxidative metabolism.", "content": "Three different vitamin E effects, suggestive of specific antioxidant effects, were discovered in the protective action of vitamin E against respiratory decline (a decrease in mitochondrial respiration attributed to a \"leakage\" of electron transport radicals). No correlation was found between respiraotry decline and random lipid peroxidation. The mechanisms behind two of the three atypical vitamin E effects were defined. Both involve an artifact in the TBA assay for lipid peroxidation. This artifact occurs when TBA assays are carried out in the presence of sucrose and acetaldehyde; the latter is produced from ethanol, the solvent used to add vitamin E to preparations. The artifact in the TBA assay for peroxidations appears also to be responsible for differing interpretations of the hepatotoxic effect of ethanol.", "contents": "Anomalous vitamin E effects in mitochondrial oxidative metabolism. Three different vitamin E effects, suggestive of specific antioxidant effects, were discovered in the protective action of vitamin E against respiratory decline (a decrease in mitochondrial respiration attributed to a \"leakage\" of electron transport radicals). No correlation was found between respiraotry decline and random lipid peroxidation. The mechanisms behind two of the three atypical vitamin E effects were defined. Both involve an artifact in the TBA assay for lipid peroxidation. This artifact occurs when TBA assays are carried out in the presence of sucrose and acetaldehyde; the latter is produced from ethanol, the solvent used to add vitamin E to preparations. The artifact in the TBA assay for peroxidations appears also to be responsible for differing interpretations of the hepatotoxic effect of ethanol."}
{"id": "PMID:215852", "title": "The hormonal induction of maturation in amphibian oocytes.", "content": "The maturation of the amphibian oocyte has been analyzed. Progesterone as well as organomercurials, lanthanum chloride and propranolol rapidly induce maturation. These chemicals are active only is applied on the cell surface. The mechanism seems to be an induction of the migration of Ca2+ from the cell membrane to the cytoplasm. K + may also play a role. Progesterone induced maturation involves synthesis of histone and histone kinase as well as several biologically active but chemically unidentified factors. cAMP does not seem to be directly involved, whereas protein phosphorylation is so.", "contents": "The hormonal induction of maturation in amphibian oocytes. The maturation of the amphibian oocyte has been analyzed. Progesterone as well as organomercurials, lanthanum chloride and propranolol rapidly induce maturation. These chemicals are active only is applied on the cell surface. The mechanism seems to be an induction of the migration of Ca2+ from the cell membrane to the cytoplasm. K + may also play a role. Progesterone induced maturation involves synthesis of histone and histone kinase as well as several biologically active but chemically unidentified factors. cAMP does not seem to be directly involved, whereas protein phosphorylation is so."}
{"id": "PMID:215853", "title": "Factors associated with utilization of the swine flu vaccination program among senior citizens in Tompkins County.", "content": "The health belief model is tested in the context of the swine flu vaccination program for senior citizens. Analysis is based on 232 responses to a questionnaire mailed to a simple random sample of 500 senior citizens in Tompkins County, New York. Social and psychologic variables identified by the model as important in determining utilization of preventive health services are: perceived susceptibility and severity of disease, perceived efficacy and danger associated with the preventive action, and general health motivations. Differences of means between users and nonusers for these variables are computed and compared with the results of a more sophisticated analytic technique--logit analysis--for use with dichotomous dependent variables. Results reveal that the health belief model accounts for 34 per cent of the variance in use of the vaccine by senior citizens. Perceived susceptibility to the disease and amount of danger associated with receiving the swine flu immunization are found to be the most important determinants of utilization.", "contents": "Factors associated with utilization of the swine flu vaccination program among senior citizens in Tompkins County. The health belief model is tested in the context of the swine flu vaccination program for senior citizens. Analysis is based on 232 responses to a questionnaire mailed to a simple random sample of 500 senior citizens in Tompkins County, New York. Social and psychologic variables identified by the model as important in determining utilization of preventive health services are: perceived susceptibility and severity of disease, perceived efficacy and danger associated with the preventive action, and general health motivations. Differences of means between users and nonusers for these variables are computed and compared with the results of a more sophisticated analytic technique--logit analysis--for use with dichotomous dependent variables. Results reveal that the health belief model accounts for 34 per cent of the variance in use of the vaccine by senior citizens. Perceived susceptibility to the disease and amount of danger associated with receiving the swine flu immunization are found to be the most important determinants of utilization."}
{"id": "PMID:215854", "title": "Administrative costs of the influenza control program of 1976--1977 in Illinois.", "content": "In 1976, many resources of state and local agencies were devoted to planning, organizing, implementing and evaluating the influenza immunization program. The costs included salaries and other expenses of specifically employed personnel; diversion of the time of others from their usual responsibilities; and donated resources. They were assessed retrospectively and reported by responsible local agency personnel on a questionnaire. Costs of donated services and other resources were estimated based on assigned unit value. The total cost of the program in Illinois was $3.334 per dose of which $1.733 was accounted for by local agencies, $0.075 by the state agency, and $1.526 by the federal government, including the cost of vaccine doses remaining unused. If the program could have been carried through to include the intended larger numbers of persons, both the administrative costs and the vaccine costs per dose administered would have been much less. The financial cost of the campaign exceeded the federal grant. It must be weighed against the administrative benefits including improved ability to conduct large scale preventive programs and awareness of the importance of both risks of benefits of immunization.", "contents": "Administrative costs of the influenza control program of 1976--1977 in Illinois. In 1976, many resources of state and local agencies were devoted to planning, organizing, implementing and evaluating the influenza immunization program. The costs included salaries and other expenses of specifically employed personnel; diversion of the time of others from their usual responsibilities; and donated resources. They were assessed retrospectively and reported by responsible local agency personnel on a questionnaire. Costs of donated services and other resources were estimated based on assigned unit value. The total cost of the program in Illinois was $3.334 per dose of which $1.733 was accounted for by local agencies, $0.075 by the state agency, and $1.526 by the federal government, including the cost of vaccine doses remaining unused. If the program could have been carried through to include the intended larger numbers of persons, both the administrative costs and the vaccine costs per dose administered would have been much less. The financial cost of the campaign exceeded the federal grant. It must be weighed against the administrative benefits including improved ability to conduct large scale preventive programs and awareness of the importance of both risks of benefits of immunization."}
{"id": "PMID:215857", "title": "[Surgery of congenital angiodysplasia (author's transl)].", "content": "Diagnostically and therapeutically, three types of angiodysplasias interfere with venous surgery: 1. Congenital arteriovenous fistulas (Type F.P. Weber: secondary varicosis with local gigantism)--surgical reduction of the shunt-volume is usually indicated. 2. Type Klippel-Trenaunay: Surgery for varicose veins is dangerous due to the frequent hypo- or aplasia of the deep venous system. 3. Venous hemangiomatosis (Type Servelle-Martorell or Kasabach-Merritt): Any surgical intervention is contraindicated (only external compressive therapy).", "contents": "[Surgery of congenital angiodysplasia (author's transl)]. Diagnostically and therapeutically, three types of angiodysplasias interfere with venous surgery: 1. Congenital arteriovenous fistulas (Type F.P. Weber: secondary varicosis with local gigantism)--surgical reduction of the shunt-volume is usually indicated. 2. Type Klippel-Trenaunay: Surgery for varicose veins is dangerous due to the frequent hypo- or aplasia of the deep venous system. 3. Venous hemangiomatosis (Type Servelle-Martorell or Kasabach-Merritt): Any surgical intervention is contraindicated (only external compressive therapy)."}
{"id": "PMID:215858", "title": "[Lung-cancer (author's transl)].", "content": "The prognosis after resection of bronchial carcinoma is not only influenced by operative techniques but by the histologic cell type, the general conditions of the patient, and specially by the stage of the disease. Therefore I recommend the routine use of mediastinoscopy, since resection of the tumor proves to be not curative in presence of perinodal growth or contralateral lymph node metastases. Followup of all patients is necessary for critical evaluation of surgical success and quality of live.", "contents": "[Lung-cancer (author's transl)]. The prognosis after resection of bronchial carcinoma is not only influenced by operative techniques but by the histologic cell type, the general conditions of the patient, and specially by the stage of the disease. Therefore I recommend the routine use of mediastinoscopy, since resection of the tumor proves to be not curative in presence of perinodal growth or contralateral lymph node metastases. Followup of all patients is necessary for critical evaluation of surgical success and quality of live."}
{"id": "PMID:215859", "title": "[Therapy of primary oat-cell carcinoma of the larynx (author's transl)].", "content": "The case of primary oat-cell carcinom of the larynx with metastases in the thyreoid gland and paratracheal lymphnodes is reported on. The different methods of treatment are examined, used examples of the much more common oat-cell carcinoma of the lung. The applicability of the methods to oat-cell carcinoma of the larynx is discussed. Our treatment scheme of surgery and extended radiation is used if the tumor is known to be locally restricted.", "contents": "[Therapy of primary oat-cell carcinoma of the larynx (author's transl)]. The case of primary oat-cell carcinom of the larynx with metastases in the thyreoid gland and paratracheal lymphnodes is reported on. The different methods of treatment are examined, used examples of the much more common oat-cell carcinoma of the lung. The applicability of the methods to oat-cell carcinoma of the larynx is discussed. Our treatment scheme of surgery and extended radiation is used if the tumor is known to be locally restricted."}
{"id": "PMID:215860", "title": "Fibrous histiocytoma of the head and neck: A case report.", "content": "Fibrous histiocytomas are soft tissue tumors of histiocytic origin. One percent prove to be malignant. Reliable histologic criteria of malignancy are few, if any, and the diagnosis of malignancy often must be made on clinical (metastases) rather than histologic grounds. Thirty-five cases originating in various deep structures of the head and neck, excluding the orbit, have been reported in the literature since 1972. One additional case, a malignant tumor of the submandibular gland, is added herewith. Recurrence following initial surgery has been common and stems from inadequate excision of the primary lesion. Microscopic spread of this tumor from its primary site calls for radical rather than conservative surgical excision. At present, radiotherapy and chemotherapy appear to be of little value in the treatment of these tumors.", "contents": "Fibrous histiocytoma of the head and neck: A case report. Fibrous histiocytomas are soft tissue tumors of histiocytic origin. One percent prove to be malignant. Reliable histologic criteria of malignancy are few, if any, and the diagnosis of malignancy often must be made on clinical (metastases) rather than histologic grounds. Thirty-five cases originating in various deep structures of the head and neck, excluding the orbit, have been reported in the literature since 1972. One additional case, a malignant tumor of the submandibular gland, is added herewith. Recurrence following initial surgery has been common and stems from inadequate excision of the primary lesion. Microscopic spread of this tumor from its primary site calls for radical rather than conservative surgical excision. At present, radiotherapy and chemotherapy appear to be of little value in the treatment of these tumors."}
{"id": "PMID:215869", "title": "Low density lipoprotein metabolism in type IV and type V hyperlipoproteinemia.", "content": "Low density lipoproteins (LDL) are thought to arise largely from degradation of triglyceride-rich very-low-density lipoproteins (VLDL). LDL kinetics in patients with Type IV and Type V hyperlipoproteinmia were studied and compared with normal subjects. LDL labeled in the protein moiety with 125I was used as a tracer. There was no significant difference in LDL turnover between the three groups, suggesting that a catabolic defect in VLDL degradation to LDL may exist in both Type IV and Type V hyperlipoproteinemia.", "contents": "Low density lipoprotein metabolism in type IV and type V hyperlipoproteinemia. Low density lipoproteins (LDL) are thought to arise largely from degradation of triglyceride-rich very-low-density lipoproteins (VLDL). LDL kinetics in patients with Type IV and Type V hyperlipoproteinmia were studied and compared with normal subjects. LDL labeled in the protein moiety with 125I was used as a tracer. There was no significant difference in LDL turnover between the three groups, suggesting that a catabolic defect in VLDL degradation to LDL may exist in both Type IV and Type V hyperlipoproteinemia."}
{"id": "PMID:215882", "title": "Studies on the pathogenicity of human-origin parainfluenza virus in the brain of mice.", "content": "The pathogenicity of parainfluenza type 2 (croup-associated) virus known to cause infections of the respiratory tract in the early life of man was studied in the brain of mice. One- to 4-day-old sucklings and 4-week-old mice were inoculated intracerebrally with the virus. The virus multiplied in sucklings, but not in adults. Most mice inoculated intracerebrally with the virus appeared healthy. Histological examination showed minimum inflammatory changes, although moderate hydrocephalus developed in three of twenty-one sucklings by 6 weeks post-infection. Immunofluorescent study in sucklings showed viral antigens in ependymal lining cells and choroid plexus epithelium during the first two weeks, and parenchymal cells for more than two months. Virus specific antibody response was observed in adults, but not in sucklings. One interesting finding was that viral antigens persisted in six out of 11 suckling brains for one to two months.", "contents": "Studies on the pathogenicity of human-origin parainfluenza virus in the brain of mice. The pathogenicity of parainfluenza type 2 (croup-associated) virus known to cause infections of the respiratory tract in the early life of man was studied in the brain of mice. One- to 4-day-old sucklings and 4-week-old mice were inoculated intracerebrally with the virus. The virus multiplied in sucklings, but not in adults. Most mice inoculated intracerebrally with the virus appeared healthy. Histological examination showed minimum inflammatory changes, although moderate hydrocephalus developed in three of twenty-one sucklings by 6 weeks post-infection. Immunofluorescent study in sucklings showed viral antigens in ependymal lining cells and choroid plexus epithelium during the first two weeks, and parenchymal cells for more than two months. Virus specific antibody response was observed in adults, but not in sucklings. One interesting finding was that viral antigens persisted in six out of 11 suckling brains for one to two months."}
{"id": "PMID:215883", "title": "Modification of immune response in nude mice infected with mouse hepatitis virus.", "content": "In nude mice experimentally infected with mouse hepatitis virus (MHV), the numbers of early and later plaque forming cells (PFC) to sheep red blood cells (SRBC) generated in the spleen were 7 to 20 times and 2 to 163 times, respectively, greater than those in non-infected nude mice, when SRBC were given at day 0 to day 21 postinfection. Splenic theta-positive lymphocytes in infected nude mice were shown to increase only at day 10 or more postinfection. PFC response to bacterial lipopolysaccharide, a T cell-independent antigen, was not modified in MHV-infected nude mice.", "contents": "Modification of immune response in nude mice infected with mouse hepatitis virus. In nude mice experimentally infected with mouse hepatitis virus (MHV), the numbers of early and later plaque forming cells (PFC) to sheep red blood cells (SRBC) generated in the spleen were 7 to 20 times and 2 to 163 times, respectively, greater than those in non-infected nude mice, when SRBC were given at day 0 to day 21 postinfection. Splenic theta-positive lymphocytes in infected nude mice were shown to increase only at day 10 or more postinfection. PFC response to bacterial lipopolysaccharide, a T cell-independent antigen, was not modified in MHV-infected nude mice."}
{"id": "PMID:215885", "title": "Liver tumours associated with oral contraceptives.", "content": "Five young women have been encountered with unusual forms of hepatic neoplasms in a ten year period. Each had been taking an oral contraceptive. Two of the four women with benign lesions noted the presence of their tumours, and another woman presented with abdominal pain. Each of these tumours was resected successfully. The fourth patient had the diagnosis made at laparotomy following the development of haemoperitoneum after an attempt at percutaneous liver biopsy. A fifth patient developed jaundice and investigation revealed a hepatocellular carcinoma which was invading the biliary tree. This experience illustrates the need for periodic physical examination of young women who are taking oral contraceptives.", "contents": "Liver tumours associated with oral contraceptives. Five young women have been encountered with unusual forms of hepatic neoplasms in a ten year period. Each had been taking an oral contraceptive. Two of the four women with benign lesions noted the presence of their tumours, and another woman presented with abdominal pain. Each of these tumours was resected successfully. The fourth patient had the diagnosis made at laparotomy following the development of haemoperitoneum after an attempt at percutaneous liver biopsy. A fifth patient developed jaundice and investigation revealed a hepatocellular carcinoma which was invading the biliary tree. This experience illustrates the need for periodic physical examination of young women who are taking oral contraceptives."}
{"id": "PMID:215887", "title": "Liver cell adenoma associated with oral contraceptive hormone therapy.", "content": "A patient receiving oral contraceptive hormone therapy developed a hepatic adenoma. Widespread haemorrhages, which were apparently unrelated to trauma, developed in the adenoma. Attention is drawn to the increasing incidence of Pill-associated hepatic tumours, and to the possibility of a fatal haemorrhage.", "contents": "Liver cell adenoma associated with oral contraceptive hormone therapy. A patient receiving oral contraceptive hormone therapy developed a hepatic adenoma. Widespread haemorrhages, which were apparently unrelated to trauma, developed in the adenoma. Attention is drawn to the increasing incidence of Pill-associated hepatic tumours, and to the possibility of a fatal haemorrhage."}
{"id": "PMID:215888", "title": "Fatal adenovirus type 7 pneumonia in an adult.", "content": "A case of fatal pneumonia caused by adenovirus type 7 in an adult is reported. This virus was isolated from the lung tissue, and typical inclusion bodies were found in histological sections. Death due to adenovirus pneumonia in adults appears to be extremely rare.", "contents": "Fatal adenovirus type 7 pneumonia in an adult. A case of fatal pneumonia caused by adenovirus type 7 in an adult is reported. This virus was isolated from the lung tissue, and typical inclusion bodies were found in histological sections. Death due to adenovirus pneumonia in adults appears to be extremely rare."}
{"id": "PMID:215889", "title": "[Glomus tumors (author's transl)].", "content": "Pathology and clinical picture of glomus tumors are described with emphasis on their location on hand and digits. It is stressed that the knowledge of this rare but extremely painful condition is essential for early treatment. Surgical treatment is standardized and simple.", "contents": "[Glomus tumors (author's transl)]. Pathology and clinical picture of glomus tumors are described with emphasis on their location on hand and digits. It is stressed that the knowledge of this rare but extremely painful condition is essential for early treatment. Surgical treatment is standardized and simple."}
{"id": "PMID:215891", "title": "Recombinational repair of alkylation lesions in phage T4. II. Ethyl methanesulfonate.", "content": "Treatment of bacteriophage T4 by ethyl methanesulfonate (EMS) caused more than a doubling in recombination between two rII markers. The functions of genes 47, 46, 32, 30, uvsX and y are known to be required for genetic recombination, and mutants defective in these genes were found to be more sensitive to inactivation by EMS than wild-type phage. This suggests that a recombinational pathway involving the products of these genes may be employed in repairing EMS induced lethal lesions. Genes 45 and denV are apparently not involved in recombination, and mutants defective in these genes were not EMS-sensitive. Gene 47, 46 and y mutants which were defective in the repair of EMS induced lethal lesions had no detectable deficiency in their ability to undergo EMS-induced mutation. This implies that recombinational repair of EMS lesions does not contribute substantially to EMS mutagenesis. The results obtained here with EMS are general similar to the results reported in the preceding paper with MNNG, suggesting that the lesions caused by both of these monofunctional alkylating agents may be eliminated by similar recombinational repair processes.", "contents": "Recombinational repair of alkylation lesions in phage T4. II. Ethyl methanesulfonate. Treatment of bacteriophage T4 by ethyl methanesulfonate (EMS) caused more than a doubling in recombination between two rII markers. The functions of genes 47, 46, 32, 30, uvsX and y are known to be required for genetic recombination, and mutants defective in these genes were found to be more sensitive to inactivation by EMS than wild-type phage. This suggests that a recombinational pathway involving the products of these genes may be employed in repairing EMS induced lethal lesions. Genes 45 and denV are apparently not involved in recombination, and mutants defective in these genes were not EMS-sensitive. Gene 47, 46 and y mutants which were defective in the repair of EMS induced lethal lesions had no detectable deficiency in their ability to undergo EMS-induced mutation. This implies that recombinational repair of EMS lesions does not contribute substantially to EMS mutagenesis. The results obtained here with EMS are general similar to the results reported in the preceding paper with MNNG, suggesting that the lesions caused by both of these monofunctional alkylating agents may be eliminated by similar recombinational repair processes."}
{"id": "PMID:215898", "title": "Carbohydrate composition of purified serum glycoproteins in mucolipidosis II and mucolipidosis III.", "content": "Mucolipidosis II (I-cell disease) and Mucolipidosis III (ML III) are inherited disorders in which the molecular defect may involve an abnormality in a common post-translational modification step (possibly glycosylation) shared by lysosomal hydrolases. We tested whether such an alteration might be a generalized defect in glycoprotein biosynthesis and, thus, be reflected in an abnormal carbohydrate composition of non-lysosomal glycoproteins. The apoprotein of low density lipoprotein (apo-LDL) and immunoglobulin G (IgG) were purified to apparent homogeneity. Gas liquid chromatographic (glc) analysis of the carbohydrate content of these glycoproteins from ML II, ML III and normal sera revealed no differences in the relative ratios and total amounts of mannose, galactose, N-acetylglucosamine and sialic acid. These results suggest that if the postulated post-translational defect in these disorders involves changes in carbohydrate composition, it is not a general defect in glycosylation and may be specific for lysosomal hydrolases.", "contents": "Carbohydrate composition of purified serum glycoproteins in mucolipidosis II and mucolipidosis III. Mucolipidosis II (I-cell disease) and Mucolipidosis III (ML III) are inherited disorders in which the molecular defect may involve an abnormality in a common post-translational modification step (possibly glycosylation) shared by lysosomal hydrolases. We tested whether such an alteration might be a generalized defect in glycoprotein biosynthesis and, thus, be reflected in an abnormal carbohydrate composition of non-lysosomal glycoproteins. The apoprotein of low density lipoprotein (apo-LDL) and immunoglobulin G (IgG) were purified to apparent homogeneity. Gas liquid chromatographic (glc) analysis of the carbohydrate content of these glycoproteins from ML II, ML III and normal sera revealed no differences in the relative ratios and total amounts of mannose, galactose, N-acetylglucosamine and sialic acid. These results suggest that if the postulated post-translational defect in these disorders involves changes in carbohydrate composition, it is not a general defect in glycosylation and may be specific for lysosomal hydrolases."}
{"id": "PMID:215899", "title": "Partial purification and characterization of cyclic nucleotide phosphodiesterases from human bronchial tissue.", "content": "DEAE-Sephadex chromatography reveals the presence in extracts of human bronchial tissue of at least three separate cyclic nucleotide phosphodiesterases: a cyclic GMP-specific high affinity enzyme, a non-specific low affinity enzyme, and a high affinity cyclic AMP-specific enzyme. The activity of each fraction was partially characterized with respect to kinetic parameters, thermal stability, and the influence of a number of inhibitors. Each activity was found to resemble the activity of the previously characterized corresponding enzyme from whole lung tissue extracts. A high affinity non-specific phospho-diesterase previously isolated from lung tissue is missing in extracts of bronchial tissue.", "contents": "Partial purification and characterization of cyclic nucleotide phosphodiesterases from human bronchial tissue. DEAE-Sephadex chromatography reveals the presence in extracts of human bronchial tissue of at least three separate cyclic nucleotide phosphodiesterases: a cyclic GMP-specific high affinity enzyme, a non-specific low affinity enzyme, and a high affinity cyclic AMP-specific enzyme. The activity of each fraction was partially characterized with respect to kinetic parameters, thermal stability, and the influence of a number of inhibitors. Each activity was found to resemble the activity of the previously characterized corresponding enzyme from whole lung tissue extracts. A high affinity non-specific phospho-diesterase previously isolated from lung tissue is missing in extracts of bronchial tissue."}
{"id": "PMID:215900", "title": "[Neurofibromatosis Recklinghausen with cerebral manifestation and deficiency of pituitary hormones (author's transl)].", "content": "In a 6 year old boy a spongioblastoma of the optic chiasm was the first manifestation of a neurofibromatosis Recklinghausen. Further characteristic symptoms developed in the following years. This central type of neurofibromatosis was combined with a decreased reserve of the hypophyseal hormones ACTH, growth hormone and FSH.", "contents": "[Neurofibromatosis Recklinghausen with cerebral manifestation and deficiency of pituitary hormones (author's transl)]. In a 6 year old boy a spongioblastoma of the optic chiasm was the first manifestation of a neurofibromatosis Recklinghausen. Further characteristic symptoms developed in the following years. This central type of neurofibromatosis was combined with a decreased reserve of the hypophyseal hormones ACTH, growth hormone and FSH."}
{"id": "PMID:215905", "title": "Apurinic and/or apyrimidinic endonuclease activity in ataxia telangiectasia cell extracts.", "content": "The possibility that the increased sensitivity of ataxia telangiectasia towards ionizing radiation is related to a DNA-repair deficiency has been examined further. When compared to unaffected controls, 6 lines of fibroblast cells derived from ataxia patients demonstrated a slightly reduced endonucleolytic activity (165 +/- 12 units vs. 214 +/- 28 units) towards apurinic and/or apyrimidinic sites as determined in a \"nicking\" assay.", "contents": "Apurinic and/or apyrimidinic endonuclease activity in ataxia telangiectasia cell extracts. The possibility that the increased sensitivity of ataxia telangiectasia towards ionizing radiation is related to a DNA-repair deficiency has been examined further. When compared to unaffected controls, 6 lines of fibroblast cells derived from ataxia patients demonstrated a slightly reduced endonucleolytic activity (165 +/- 12 units vs. 214 +/- 28 units) towards apurinic and/or apyrimidinic sites as determined in a \"nicking\" assay."}
{"id": "PMID:215906", "title": "Ethylation of DNA and protamine by ethyl methanesulfonate in the germ cells of male mice and the relevancy of these molecular targets to the induction of dominant lethals.", "content": "The molecular dosimetry of ethyl methanesulfonate (EMS) in the germ cells of male mice has been investigated. The mice were injected i.p. with 200 mg/kg of [3H]EMS and the ethylations per sperm head, per deoxynucleotide, and per unit of protamine were then determined over a 2-week period. The ethylations per sperm head closely paralleled the dominant-lethal frequency curve for EMS, reaching a maximum of 5 to 6.5 million ethylations per vas sperm head at 8 to 10 days after treatment. Ethylation of sperm DNA was greatest at 4 h after treatment, with 5.7 ethylations/10(5) deoxynucleotides, and gradually decreased to 2.2 ethylations/10(5) deoxynucleotides at 15 days after treatment. The ethylation of sperm DNA did not increase in the germ-cell stages most sensitive to EMS, and was not correlated with the dominant-lethal frequency curve for EMS. However, ethylation of sperm protamine did increase in the germ-cell stages most sensitive to EMS, and showed an excellent correlation with the incidence of dominant lethals produced by EMS in the germ cells. A model is presented to explain, at a molecular level, how dominant lethals may be induced in mouse germ cells by EMS. Ethylation of cysteine sulfhydryl groups contained in mouse-sperm protamine could block normal disulfide-bond formation, preventing proper chromatin condensation in the sperm nucleus. Stresses in the chromatin structure could then eventually lead to chromosome breakage, with resultant dominant lethality.", "contents": "Ethylation of DNA and protamine by ethyl methanesulfonate in the germ cells of male mice and the relevancy of these molecular targets to the induction of dominant lethals. The molecular dosimetry of ethyl methanesulfonate (EMS) in the germ cells of male mice has been investigated. The mice were injected i.p. with 200 mg/kg of [3H]EMS and the ethylations per sperm head, per deoxynucleotide, and per unit of protamine were then determined over a 2-week period. The ethylations per sperm head closely paralleled the dominant-lethal frequency curve for EMS, reaching a maximum of 5 to 6.5 million ethylations per vas sperm head at 8 to 10 days after treatment. Ethylation of sperm DNA was greatest at 4 h after treatment, with 5.7 ethylations/10(5) deoxynucleotides, and gradually decreased to 2.2 ethylations/10(5) deoxynucleotides at 15 days after treatment. The ethylation of sperm DNA did not increase in the germ-cell stages most sensitive to EMS, and was not correlated with the dominant-lethal frequency curve for EMS. However, ethylation of sperm protamine did increase in the germ-cell stages most sensitive to EMS, and showed an excellent correlation with the incidence of dominant lethals produced by EMS in the germ cells. A model is presented to explain, at a molecular level, how dominant lethals may be induced in mouse germ cells by EMS. Ethylation of cysteine sulfhydryl groups contained in mouse-sperm protamine could block normal disulfide-bond formation, preventing proper chromatin condensation in the sperm nucleus. Stresses in the chromatin structure could then eventually lead to chromosome breakage, with resultant dominant lethality."}
{"id": "PMID:215912", "title": "Treatment of Cushing's disease by O,p'DDD. Survey of 62 cases.", "content": "In a study of nonsurgical therapy of Cushing's disease, 62 patients received O,p'-dichlorodiphenyldichloroethane (O,p'DDD), 16 of whom also received cobalt irradiation of the pituitary. After an initial treatment period averaging eight months, a remission of the disease was obtained in 38 of the 46 patients given O,p'DDD alone and in all patients who received drug combined with radiation. Although 60 per cent of these patients subsequently relapsed, additional courses of drug or radiation therapy were usually effective, and 63 per cent of the entire group of patients have so far been kept under control without adrenalectomy. (Forty patients have been followed for at least two years after the initial course of treatment.). O,p'DDD produced little gastrointestinal discomfort; an increased serum cholesterol was the main side effect. This drug allows long-term medical management of Cushings disease in most cases. Whether the combination of O'p'DDD with pituitary radiation is the best therapy has not been established.", "contents": "Treatment of Cushing's disease by O,p'DDD. Survey of 62 cases. In a study of nonsurgical therapy of Cushing's disease, 62 patients received O,p'-dichlorodiphenyldichloroethane (O,p'DDD), 16 of whom also received cobalt irradiation of the pituitary. After an initial treatment period averaging eight months, a remission of the disease was obtained in 38 of the 46 patients given O,p'DDD alone and in all patients who received drug combined with radiation. Although 60 per cent of these patients subsequently relapsed, additional courses of drug or radiation therapy were usually effective, and 63 per cent of the entire group of patients have so far been kept under control without adrenalectomy. (Forty patients have been followed for at least two years after the initial course of treatment.). O,p'DDD produced little gastrointestinal discomfort; an increased serum cholesterol was the main side effect. This drug allows long-term medical management of Cushings disease in most cases. Whether the combination of O'p'DDD with pituitary radiation is the best therapy has not been established."}
{"id": "PMID:215915", "title": "Synthesis of rabbit beta-globin in cultured monkey kidney cells following infection with a SV40 beta-globin recombinant genome.", "content": "Rabbit beta-globin complementary DNA (cDNA) has been inserted into SV40 DNA in place of the gene coding for the virus' major capsid protein, VP1. The recombinant genome, SVGT5-RabetaG, multiplies efficiently in CV1 monkey kidney cell cultures and is transcribed to yield cytoplasmic, polyadenylated hybrid mRNAs containing the beta-globin coding sequence. Cells propagating SVGT5-RabetaG produce substantial quantities of rabbit beta-globin polypeptide.", "contents": "Synthesis of rabbit beta-globin in cultured monkey kidney cells following infection with a SV40 beta-globin recombinant genome. Rabbit beta-globin complementary DNA (cDNA) has been inserted into SV40 DNA in place of the gene coding for the virus' major capsid protein, VP1. The recombinant genome, SVGT5-RabetaG, multiplies efficiently in CV1 monkey kidney cell cultures and is transcribed to yield cytoplasmic, polyadenylated hybrid mRNAs containing the beta-globin coding sequence. Cells propagating SVGT5-RabetaG produce substantial quantities of rabbit beta-globin polypeptide."}
{"id": "PMID:215922", "title": "On spare beta-adrenoceptors of inotropic effect of catecholamines in kitten ventricle.", "content": "Beta-Adrenoceptors of ventricular membranes of kitten heart were labelled reversibly with (--)-3H-propranolol (binding constant 6nM). Bound (--)-3H-propranolol was displaced with beta-adrenoceptor blocking agents and catecholamines. Displacement constants KD(M) of the blockers were of the same of magnitude as their constants KB obtained from the antagonism of inotropic effects of catecholamines in papillary muscles. KD's of catecholamines were, however, 2 orders of magnitude larger than concentrations causing half maximal inotropic effects, indicating large spare beta-adrenoceptor capacity.", "contents": "On spare beta-adrenoceptors of inotropic effect of catecholamines in kitten ventricle. Beta-Adrenoceptors of ventricular membranes of kitten heart were labelled reversibly with (--)-3H-propranolol (binding constant 6nM). Bound (--)-3H-propranolol was displaced with beta-adrenoceptor blocking agents and catecholamines. Displacement constants KD(M) of the blockers were of the same of magnitude as their constants KB obtained from the antagonism of inotropic effects of catecholamines in papillary muscles. KD's of catecholamines were, however, 2 orders of magnitude larger than concentrations causing half maximal inotropic effects, indicating large spare beta-adrenoceptor capacity."}
{"id": "PMID:215924", "title": "[Immunocytochemical localization of the GFAP in heterotransplanted human gliomas (author's transl)].", "content": "Three cell lines derived in our laboratory from human malignant gliomas (SA 130, SA 132, SA 134) were injected subcutaneously into pathogen-free nude thymus less mice. These three cell lines gave origine to malignant tumors which, as original tumors, were positive for the glial fibrillary acidic protein (GFAP) revealed by immunoperoxidase method.", "contents": "[Immunocytochemical localization of the GFAP in heterotransplanted human gliomas (author's transl)]. Three cell lines derived in our laboratory from human malignant gliomas (SA 130, SA 132, SA 134) were injected subcutaneously into pathogen-free nude thymus less mice. These three cell lines gave origine to malignant tumors which, as original tumors, were positive for the glial fibrillary acidic protein (GFAP) revealed by immunoperoxidase method."}
{"id": "PMID:215925", "title": "[Study of the relationship between intracr\u00e2nial pressure and paradoxal sleep in the cat (author's transl].", "content": "The present study reports on the modification of the intracranial pressure (ICP) during rapid eye movements (REM) sleep in seven chronic cats. 1. REM sleep episodes were characterized by a succession of short lasting (9 +/- 4 seconds) oscillations of the ICP. Peaks amplitude represented a hundred percent increase of the pressure as compared to its resting level. 2. These oscillations either arose from an ICP level similar to that recorded during the preceding slow wave sleep period or were seen to overide a wave of raised ICP that lasted throughout the REM period. 3. Eighty eight percent of the phasic oscillation coincided with a burt of eye movement characteristic of REM sleep. 4. Cerebral pulse wave amplitude can vary for identical ICP mean value in the course of a same REM period.", "contents": "[Study of the relationship between intracr\u00e2nial pressure and paradoxal sleep in the cat (author's transl]. The present study reports on the modification of the intracranial pressure (ICP) during rapid eye movements (REM) sleep in seven chronic cats. 1. REM sleep episodes were characterized by a succession of short lasting (9 +/- 4 seconds) oscillations of the ICP. Peaks amplitude represented a hundred percent increase of the pressure as compared to its resting level. 2. These oscillations either arose from an ICP level similar to that recorded during the preceding slow wave sleep period or were seen to overide a wave of raised ICP that lasted throughout the REM period. 3. Eighty eight percent of the phasic oscillation coincided with a burt of eye movement characteristic of REM sleep. 4. Cerebral pulse wave amplitude can vary for identical ICP mean value in the course of a same REM period."}
{"id": "PMID:215926", "title": "[Significance of computed tomography in therapeutic diagnosis of brain tumors (author's transl)].", "content": "Because of its noninvasive property of direct imaging of the size and shape of the lesion, CT scan is significant not only for the diagnosis of the brain tumors, but also for the assessment of its chronological and/or therapeutic change in size. Contrary to the conventional cerebral angiography and contrast encephalography, CT scan is feasible to detect the tumor repeatedly at short intervals. From March 1976 to October 1977, 197 cases of brain tumors were examined by CT, 6 tumors (1 pineal tumor, 2 cerebellar vermian tumors and 3 supratentorial tumors) of which were radiated after the initial CT scan and re-examined by CT at every 400-1,000 rads radiation, and their grade of radiosensitivity could be evaluated. Immediately after the radiation of 400 rads for five days to the large pineal tumor of a 16-year-old boy, CT exactly showed the markedly diminished size of the tumor, and the tumor disappeared on CT after the 4,000 rads radiation. Cerebellar vermian tumors suspected of medulloblastoma were also diminished in size on CT after the 600 rads radiation. One supratentorial tumor was radiosensitive and disappeared at the end of radiation therapy. Other supratentorial tumors were not changed on CT during the radiation. Procedures for the therapeutic diagnosis, when combined with CT, can easily indicate whether the tumor is radiosensitive or not, without any invasive examination and/or operation.", "contents": "[Significance of computed tomography in therapeutic diagnosis of brain tumors (author's transl)]. Because of its noninvasive property of direct imaging of the size and shape of the lesion, CT scan is significant not only for the diagnosis of the brain tumors, but also for the assessment of its chronological and/or therapeutic change in size. Contrary to the conventional cerebral angiography and contrast encephalography, CT scan is feasible to detect the tumor repeatedly at short intervals. From March 1976 to October 1977, 197 cases of brain tumors were examined by CT, 6 tumors (1 pineal tumor, 2 cerebellar vermian tumors and 3 supratentorial tumors) of which were radiated after the initial CT scan and re-examined by CT at every 400-1,000 rads radiation, and their grade of radiosensitivity could be evaluated. Immediately after the radiation of 400 rads for five days to the large pineal tumor of a 16-year-old boy, CT exactly showed the markedly diminished size of the tumor, and the tumor disappeared on CT after the 4,000 rads radiation. Cerebellar vermian tumors suspected of medulloblastoma were also diminished in size on CT after the 600 rads radiation. One supratentorial tumor was radiosensitive and disappeared at the end of radiation therapy. Other supratentorial tumors were not changed on CT during the radiation. Procedures for the therapeutic diagnosis, when combined with CT, can easily indicate whether the tumor is radiosensitive or not, without any invasive examination and/or operation."}
{"id": "PMID:215927", "title": "[Surgical treatment of hemifacial spasm associated with tortuous vertebrobasilar system (author's transl)].", "content": "Surgical treatment of hemifacial spasm associated with tortuous vertebrobasilar system was reported. A patient was 63-year-old female, who first experienced mild and intermittent muscle twitching around her left eye twenty years prior to admission. Five years later, the twitching extended to all the facial muscles on the left side. She was treated with facial nerve block, which resulted in facial palsy for about one year. Because of recurrence of the hemifacial spasm, she was admitted to the Neurosurgical Department of Bokuto Municipal Hospital on October 12, 1977. Neurological examination revealed no abnormalities except for left hemifacial spasm with slight muscular weakness. Electromyogram showed severe twitching and synkinesis of all the muscles of facial expression. Vertebral angiogram on the left side disclosed pronounced elongation of the vertebral and basilar arteries, which extended into the left cerebellopontine angle. Compression of the facial nerve root exit zone at the brainstem by the vertebral artery was considered to be the cause of the hemifacial spasm. Suboccipital craniectomy was carried out on November 29, 1977. The vertebral artery extended into the cerebellopontine angle, and adhered to the facial nerve. After mobilization of the vertebral artery from the facial nerve, a small prosthesis of non-absorbable spongy material (Teflon felt) was interposed between the vertebral artery and brainstem. Postoperatively, the hemifacial spasm disappeared, but the facial palsy, which had been observed preoperatively probably due to previous facial nerve block and long-standing hemifacial spasm, remained. The function of the acoustic nerve was preserved. Recently vascular compression of the facial nerve root exit zone has been reported as a major cause of hemifacial spasm, but such abnormal vessels are rarely demonstrated angiographically.", "contents": "[Surgical treatment of hemifacial spasm associated with tortuous vertebrobasilar system (author's transl)]. Surgical treatment of hemifacial spasm associated with tortuous vertebrobasilar system was reported. A patient was 63-year-old female, who first experienced mild and intermittent muscle twitching around her left eye twenty years prior to admission. Five years later, the twitching extended to all the facial muscles on the left side. She was treated with facial nerve block, which resulted in facial palsy for about one year. Because of recurrence of the hemifacial spasm, she was admitted to the Neurosurgical Department of Bokuto Municipal Hospital on October 12, 1977. Neurological examination revealed no abnormalities except for left hemifacial spasm with slight muscular weakness. Electromyogram showed severe twitching and synkinesis of all the muscles of facial expression. Vertebral angiogram on the left side disclosed pronounced elongation of the vertebral and basilar arteries, which extended into the left cerebellopontine angle. Compression of the facial nerve root exit zone at the brainstem by the vertebral artery was considered to be the cause of the hemifacial spasm. Suboccipital craniectomy was carried out on November 29, 1977. The vertebral artery extended into the cerebellopontine angle, and adhered to the facial nerve. After mobilization of the vertebral artery from the facial nerve, a small prosthesis of non-absorbable spongy material (Teflon felt) was interposed between the vertebral artery and brainstem. Postoperatively, the hemifacial spasm disappeared, but the facial palsy, which had been observed preoperatively probably due to previous facial nerve block and long-standing hemifacial spasm, remained. The function of the acoustic nerve was preserved. Recently vascular compression of the facial nerve root exit zone has been reported as a major cause of hemifacial spasm, but such abnormal vessels are rarely demonstrated angiographically."}
{"id": "PMID:215928", "title": "Effect of norepinephrine on renin release and the cyclic AMP content of rat kidney slices: modification by sodium deficiency and alpha-adrenergic blockade.", "content": "The effect of L-norepinephrine (NE) on renin release by slices of kidney cortex from sodium-replete and sodium-deficient rats was studied in vitro. The rate of renin release by slices from sodium-deficient rats in the absence of added NE increased in proportion to the length of dietary sodium restriction and was significantly greater at all times than release by slices from sodium-replete animals. NE added to slices from the sodium-replete animals in concentrations ranging from 2 X 10(-9) to 2 X 10(-4)M caused a significant renin release only at a concentration of 2 X 10(-7)M. In contrast, the rate of renin release by slices from the sodium-deficient rats increased in a dose-related fashion when the NE concentration ranged from 2 X 10(-12) to 2 X 10(-7)M. NE in a concentration of 2 X 10(-5) had a lesser stimulatory effect, and 2 X 10(-4)M caused a significant inhibition of renin release. This inhibition was converted to stimulation by addition of the alpha-adrenergic blocking drug phentolamine. Phentolamine by itself was ineffective. The increases and decreases in renin release produced by NE were, in general, accompanied by increases and decreases in the cyclic AMP content of the slices. The changes in renin release were linear for 60 min, but the changes in cyclic AMP content were greater at 5 and 20 min than at 60 min. A dose-response relationship between the changes in renin release and cyclic AMP content was not observed. These data indicate that sodium deprivation enhances the sensitivity of the renin-secreting cells to catecholamine stimulation, and are consistent with the hypothesis that the increase in renin secretion produced by NE is mediated via cyclic AMP. The data also indicated that in high concentrations, NE exerts an inhibitory effect on renin release, and that this effect is mediated via stimulation of alpha-adrenergic receptors.", "contents": "Effect of norepinephrine on renin release and the cyclic AMP content of rat kidney slices: modification by sodium deficiency and alpha-adrenergic blockade. The effect of L-norepinephrine (NE) on renin release by slices of kidney cortex from sodium-replete and sodium-deficient rats was studied in vitro. The rate of renin release by slices from sodium-deficient rats in the absence of added NE increased in proportion to the length of dietary sodium restriction and was significantly greater at all times than release by slices from sodium-replete animals. NE added to slices from the sodium-replete animals in concentrations ranging from 2 X 10(-9) to 2 X 10(-4)M caused a significant renin release only at a concentration of 2 X 10(-7)M. In contrast, the rate of renin release by slices from the sodium-deficient rats increased in a dose-related fashion when the NE concentration ranged from 2 X 10(-12) to 2 X 10(-7)M. NE in a concentration of 2 X 10(-5) had a lesser stimulatory effect, and 2 X 10(-4)M caused a significant inhibition of renin release. This inhibition was converted to stimulation by addition of the alpha-adrenergic blocking drug phentolamine. Phentolamine by itself was ineffective. The increases and decreases in renin release produced by NE were, in general, accompanied by increases and decreases in the cyclic AMP content of the slices. The changes in renin release were linear for 60 min, but the changes in cyclic AMP content were greater at 5 and 20 min than at 60 min. A dose-response relationship between the changes in renin release and cyclic AMP content was not observed. These data indicate that sodium deprivation enhances the sensitivity of the renin-secreting cells to catecholamine stimulation, and are consistent with the hypothesis that the increase in renin secretion produced by NE is mediated via cyclic AMP. The data also indicated that in high concentrations, NE exerts an inhibitory effect on renin release, and that this effect is mediated via stimulation of alpha-adrenergic receptors."}
{"id": "PMID:215929", "title": "In vitro release of ACTH from dispersed rat pars intermedia cells. III. Multiple forms of ACTH biological activity.", "content": "We have reported that both an extract of rat hypothalamus-stalk-median eminence (HE) and 5-hydroxytryptamine (5-HT) will stimulate the release of ACTH biological activity from acutely, non-enzymically dispersed rat pars intermedia (PI) cells. We have also found that the ACTH activity within the PI cells is composed of 4 chromatographically separable entities, but only a small proportion of the total ACTH activity co-elutes with ACTH1-39. In the present study we subjected the media, after incubation of PI cells with either HE or 5-HT, to sequential chromatography on Sephadex G-50 F and G-100 SF. We found the same 4 ACTH-like moieties as in the PI cell extracts. Only the release of the 2 earliest eluting components, presumably of much larger molecular dimensions than ACTH1-39, was enhanced by either HE or 5-HT. There was no augmented release of the ACTH component having molecular dimensions similar to ACTH1-39. Thus, in our in vitro system, the ACTH biological activity released from PI cells is not the size of ACTH1-39, but is composed of at least 2 much larger molecules which possess ACTH (as well as some MSH) biological activity.", "contents": "In vitro release of ACTH from dispersed rat pars intermedia cells. III. Multiple forms of ACTH biological activity. We have reported that both an extract of rat hypothalamus-stalk-median eminence (HE) and 5-hydroxytryptamine (5-HT) will stimulate the release of ACTH biological activity from acutely, non-enzymically dispersed rat pars intermedia (PI) cells. We have also found that the ACTH activity within the PI cells is composed of 4 chromatographically separable entities, but only a small proportion of the total ACTH activity co-elutes with ACTH1-39. In the present study we subjected the media, after incubation of PI cells with either HE or 5-HT, to sequential chromatography on Sephadex G-50 F and G-100 SF. We found the same 4 ACTH-like moieties as in the PI cell extracts. Only the release of the 2 earliest eluting components, presumably of much larger molecular dimensions than ACTH1-39, was enhanced by either HE or 5-HT. There was no augmented release of the ACTH component having molecular dimensions similar to ACTH1-39. Thus, in our in vitro system, the ACTH biological activity released from PI cells is not the size of ACTH1-39, but is composed of at least 2 much larger molecules which possess ACTH (as well as some MSH) biological activity."}
{"id": "PMID:215930", "title": "ACTH release after tuberal electrical stimulation in rats with various cuts around the medial basal hypothalamus.", "content": "After the combined treatment with dexamethasone, morphine and pentobarbitone, the electrical stimulation in the rat tuber cinereum induces a rise in plasma corticosterone (CS) level, probably by direct stimulation of the corticoliberin-producing neural elements and the consecutive ACTH release. We have attempted to locate these corticoliberin-containing neural elements by electrical stimulation in rats with various surgical cuts (deafferentations) around the medial basal hypothalamus (MBH). Seven to eight days after the complete circumsection of the MBH, the electrical stimulation of the isolated region did not affect plasma CS level. Also, the electrical excitation proved to be ineffective after antero-lateral or only lateral sections that interrupted the fibers running through the lateral region of the retrochiasmatic area. In contrast, a rise in CS level followed electrical stimulation of rats with anterolateral transections, provided the basal part of the lateral retrochiasmatic area stayed intact. We suggest that fibers traversing the basal region of the lateral retrochiasmatic area have a major role in the release of corticoliberin from the median eminence (ME).", "contents": "ACTH release after tuberal electrical stimulation in rats with various cuts around the medial basal hypothalamus. After the combined treatment with dexamethasone, morphine and pentobarbitone, the electrical stimulation in the rat tuber cinereum induces a rise in plasma corticosterone (CS) level, probably by direct stimulation of the corticoliberin-producing neural elements and the consecutive ACTH release. We have attempted to locate these corticoliberin-containing neural elements by electrical stimulation in rats with various surgical cuts (deafferentations) around the medial basal hypothalamus (MBH). Seven to eight days after the complete circumsection of the MBH, the electrical stimulation of the isolated region did not affect plasma CS level. Also, the electrical excitation proved to be ineffective after antero-lateral or only lateral sections that interrupted the fibers running through the lateral region of the retrochiasmatic area. In contrast, a rise in CS level followed electrical stimulation of rats with anterolateral transections, provided the basal part of the lateral retrochiasmatic area stayed intact. We suggest that fibers traversing the basal region of the lateral retrochiasmatic area have a major role in the release of corticoliberin from the median eminence (ME)."}
{"id": "PMID:215931", "title": "Corticotropin responsiveness in the neonatal rat.", "content": "Plasma ACTH concentrations were determined in neonatal rats 1, 7, 14, and 21 days old, subjected to treatment with either a median eminence extract with corticotropin releasing factor (CRF) activity or to ether exposure. 'CRF' injection elevated plasma ACTH levels on all days tested. Ether exposure elevated ACTH levels on days 14 and 21, but not on days 1 or 7. These results indicate: (1) that there is no diminution of responsiveness of the pituitary to direct stimulation by CRF as a function of age, and (2) that the mediators of the stress response above the level of the pituitary are not functionally mature until approximately day 14. Correlations with previous studies also indicate that there is a delay in the return of adrenal responsiveness until some time after these mediators attain maturity.", "contents": "Corticotropin responsiveness in the neonatal rat. Plasma ACTH concentrations were determined in neonatal rats 1, 7, 14, and 21 days old, subjected to treatment with either a median eminence extract with corticotropin releasing factor (CRF) activity or to ether exposure. 'CRF' injection elevated plasma ACTH levels on all days tested. Ether exposure elevated ACTH levels on days 14 and 21, but not on days 1 or 7. These results indicate: (1) that there is no diminution of responsiveness of the pituitary to direct stimulation by CRF as a function of age, and (2) that the mediators of the stress response above the level of the pituitary are not functionally mature until approximately day 14. Correlations with previous studies also indicate that there is a delay in the return of adrenal responsiveness until some time after these mediators attain maturity."}
{"id": "PMID:215932", "title": "The influence of diurnal rhythms in patients with intracranial hypertension: implications for management.", "content": "Decompensation of brain injured patients during the night is common and has been attributed to the retention of CO2 during sleep. When CO2 is controlled, such nocturnal decompensation needs another explanation; consequently, the records of 21 consecutive patients with acute closed head injuries and increased intracranial pressure were reviewed. There were 185 separate episodes of intracranial hypertension (30 mm Hg or more for 10 minutes or more) in the 21 patients, 124 of which (67%) occurred between 4:00 a.m. and 9:00 a.m. (p less than 0.01). Intravenous pentobarbital (3 to 5 mg/kg) was effective in reducing the intracranial pressure (ICP) to normal levels during 104 of the 124 early morning episodes (84%), whereas mannitol was less effective (7 of 17; 41%). This suggests that an increase in brain blood volume directly related to diurnal rhythm is responsible for the increase in ICP. Severe bradycardia and systemic arterial hypertension were unreliable predictors of elevation in ICP. They preceded or accompanied less than one-fourth of the episodes.", "contents": "The influence of diurnal rhythms in patients with intracranial hypertension: implications for management. Decompensation of brain injured patients during the night is common and has been attributed to the retention of CO2 during sleep. When CO2 is controlled, such nocturnal decompensation needs another explanation; consequently, the records of 21 consecutive patients with acute closed head injuries and increased intracranial pressure were reviewed. There were 185 separate episodes of intracranial hypertension (30 mm Hg or more for 10 minutes or more) in the 21 patients, 124 of which (67%) occurred between 4:00 a.m. and 9:00 a.m. (p less than 0.01). Intravenous pentobarbital (3 to 5 mg/kg) was effective in reducing the intracranial pressure (ICP) to normal levels during 104 of the 124 early morning episodes (84%), whereas mannitol was less effective (7 of 17; 41%). This suggests that an increase in brain blood volume directly related to diurnal rhythm is responsible for the increase in ICP. Severe bradycardia and systemic arterial hypertension were unreliable predictors of elevation in ICP. They preceded or accompanied less than one-fourth of the episodes."}
{"id": "PMID:215933", "title": "Fluorometric monitoring of NADH levels in cerebral cortex: preliminary observations in human epilepsy.", "content": "In 14 patients operated upon for focal cerebral seizures under local anesthesia, cortical electrical activity was compared with the levels of nicotinamide adenine dinucleotide (NADH) observed fluorometrically. NADH levels fell 3 to 15% in response to 5-second intervals of cortical stimulation in 42 of 70 observations. Although a rough correlation was seen between the quantity of current delivered (milliamperes X seconds) and the NADH decrease, this varied from case to case. The presence of cortical afterdischarge often, but not invariably, corresponded to a greater percentage of change in the NADH levels. Averaging the NADH response to sporadic interictal epileptiform discharges failed to demonstrate concomitant NADH reductions. A similar lack of change was seen in four patients in whom low frequency spike foci were induced by topically applied penicillin in cortex destined for excision. Preliminary studies of the topography of spread of NADH change after cortical stimulation indicate that this is usually asymmetrical in human epileptogenic cortex. Under experimental conditions in cats, it seemed possible to differentiate primary from projected epileptiform activity, in that the projected activity had little or no concomitant fall in the NADH level after the electrographic spike. Pathological examination of the excised sites of NADH recording showed, with one exception, fibrous astrocytic transformation of the central cortex layers.", "contents": "Fluorometric monitoring of NADH levels in cerebral cortex: preliminary observations in human epilepsy. In 14 patients operated upon for focal cerebral seizures under local anesthesia, cortical electrical activity was compared with the levels of nicotinamide adenine dinucleotide (NADH) observed fluorometrically. NADH levels fell 3 to 15% in response to 5-second intervals of cortical stimulation in 42 of 70 observations. Although a rough correlation was seen between the quantity of current delivered (milliamperes X seconds) and the NADH decrease, this varied from case to case. The presence of cortical afterdischarge often, but not invariably, corresponded to a greater percentage of change in the NADH levels. Averaging the NADH response to sporadic interictal epileptiform discharges failed to demonstrate concomitant NADH reductions. A similar lack of change was seen in four patients in whom low frequency spike foci were induced by topically applied penicillin in cortex destined for excision. Preliminary studies of the topography of spread of NADH change after cortical stimulation indicate that this is usually asymmetrical in human epileptogenic cortex. Under experimental conditions in cats, it seemed possible to differentiate primary from projected epileptiform activity, in that the projected activity had little or no concomitant fall in the NADH level after the electrographic spike. Pathological examination of the excised sites of NADH recording showed, with one exception, fibrous astrocytic transformation of the central cortex layers."}
{"id": "PMID:215934", "title": "Growth-inhibitory effects of diphenylhydantoin on human brain tumor cells in culture.", "content": "Diphenylhydantoin (DPH, phenytoin sodium, Dilantin) inhibited the growth of cultured human astrocytoma cells in 7 of the 10 cell lines studied. This inhibition, determined by a microtiter assay, was dose-dependent; DPH levels of 20 micrograms/ml and above produced significant depression of growth in astrocytoma cultured cells. However, normal cultured human astrocytes were not affected until DPH levels of 60 micrograms/ml and above were added to the cells; normal fibroblasts also showed no growth inhibition up to 100 micrograms/ml. We have confirmed that DPH is 1.5 times as concentrated in tumor tissue as it is in normal tissue and serum. These findings suggest that DPH has properties that inhibit the growth of human astrocytoma cells in tissue culture at levels that are achievable clinically.", "contents": "Growth-inhibitory effects of diphenylhydantoin on human brain tumor cells in culture. Diphenylhydantoin (DPH, phenytoin sodium, Dilantin) inhibited the growth of cultured human astrocytoma cells in 7 of the 10 cell lines studied. This inhibition, determined by a microtiter assay, was dose-dependent; DPH levels of 20 micrograms/ml and above produced significant depression of growth in astrocytoma cultured cells. However, normal cultured human astrocytes were not affected until DPH levels of 60 micrograms/ml and above were added to the cells; normal fibroblasts also showed no growth inhibition up to 100 micrograms/ml. We have confirmed that DPH is 1.5 times as concentrated in tumor tissue as it is in normal tissue and serum. These findings suggest that DPH has properties that inhibit the growth of human astrocytoma cells in tissue culture at levels that are achievable clinically."}
{"id": "PMID:215939", "title": "Effect of denervation on coxsackie A virus myositis in mice: an electronmicroscopic study.", "content": "Myositis induced by Coxsackie A4 and A9 viruses was investigated in the gastrocnemius muscles of suckling mice and adult mice with denervation. Denervation markedly increased the susceptibility of adult mice to Coxsackie A virus infection, and this effect was initiated as early as 1 day after denervation. Light microscopy demonstrated inflammation and necrosis in the denervated gastrocnemius muscle of adult mice, whereas muscle from the contralateral leg showed only infrequent, mild, focal myositis. Ultrastructually, crystalline arrays of virus particles were seen in the infected muscle fibers and in the phagocytes of both suckling and adult mice. Nuclear alterations, especially in the myotubes, and a characteristic compound membrane-vesicle complex (CMVC) in the sarcoplasm, developed simultaneously. Replicating and fusing myoblasts, activated as part of the regenerative process after denervation, appeared to be closely associated with the susceptibility of muscle to Coxsackie A virus infection.", "contents": "Effect of denervation on coxsackie A virus myositis in mice: an electronmicroscopic study. Myositis induced by Coxsackie A4 and A9 viruses was investigated in the gastrocnemius muscles of suckling mice and adult mice with denervation. Denervation markedly increased the susceptibility of adult mice to Coxsackie A virus infection, and this effect was initiated as early as 1 day after denervation. Light microscopy demonstrated inflammation and necrosis in the denervated gastrocnemius muscle of adult mice, whereas muscle from the contralateral leg showed only infrequent, mild, focal myositis. Ultrastructually, crystalline arrays of virus particles were seen in the infected muscle fibers and in the phagocytes of both suckling and adult mice. Nuclear alterations, especially in the myotubes, and a characteristic compound membrane-vesicle complex (CMVC) in the sarcoplasm, developed simultaneously. Replicating and fusing myoblasts, activated as part of the regenerative process after denervation, appeared to be closely associated with the susceptibility of muscle to Coxsackie A virus infection."}
{"id": "PMID:215935", "title": "Stereotactic localization (with computerized tomographic scanning), biopsy, and radiofrequency treatment of deep brain lesions.", "content": "In eight patients stereotactic biopsy of deep brain lesions was performed. Adequate tissue was obtained, and the information helped considerably in planning further therapy. No significant complications occurred in these patients. In three of the cases, the stereotactic coordinates were determined from the computerized tomographic (CT) scan. In one patient, after biopsy, stereotactic radiofrequency (RF) lesions in the tumor resulted in temporary improvement.", "contents": "Stereotactic localization (with computerized tomographic scanning), biopsy, and radiofrequency treatment of deep brain lesions. In eight patients stereotactic biopsy of deep brain lesions was performed. Adequate tissue was obtained, and the information helped considerably in planning further therapy. No significant complications occurred in these patients. In three of the cases, the stereotactic coordinates were determined from the computerized tomographic (CT) scan. In one patient, after biopsy, stereotactic radiofrequency (RF) lesions in the tumor resulted in temporary improvement."}
{"id": "PMID:215940", "title": "Firing rates of human motor units in partially denervated muscle.", "content": "Single motor unit firing rates were measured from the first dorsal interosseous muscle (FDI) of normal subjects and patients with partial denervation of that muscle. Motor unit discharges were recorded at various levels of voluntary, stationary, isometric contraction of the FDI. The mean increase in firing rate associated with an increased muscle tension of 100 gm was significantly greater in severely weak muscle. However, when an \"adjustment\" was made for the degree of weakness, reduced firing rate responses were observed which correlated with the degree of muscle weakness.", "contents": "Firing rates of human motor units in partially denervated muscle. Single motor unit firing rates were measured from the first dorsal interosseous muscle (FDI) of normal subjects and patients with partial denervation of that muscle. Motor unit discharges were recorded at various levels of voluntary, stationary, isometric contraction of the FDI. The mean increase in firing rate associated with an increased muscle tension of 100 gm was significantly greater in severely weak muscle. However, when an \"adjustment\" was made for the degree of weakness, reduced firing rate responses were observed which correlated with the degree of muscle weakness."}
{"id": "PMID:215941", "title": "Isolated trigeminal sensory neuropathy: early manifestation of mixed connective tissue disease.", "content": "A young woman with mixed connective tissue disease (MCTD) had an isolated trigeminal sensory neuropathy as an early manifestation of the disease. Raynaud phenomenon occurred almost synchronously with the onset of trigeminal neuropathy and was followed by myositis, diffuse hand swelling, synovitis, and increased ribonucleoprotein antibody. Mixed connective tissue disease has overlapping features of systemic lupus erythematosus, scleroderma, and polymyositis, and is differentiated from them by high-titer antibody to ribonucleoprotein.", "contents": "Isolated trigeminal sensory neuropathy: early manifestation of mixed connective tissue disease. A young woman with mixed connective tissue disease (MCTD) had an isolated trigeminal sensory neuropathy as an early manifestation of the disease. Raynaud phenomenon occurred almost synchronously with the onset of trigeminal neuropathy and was followed by myositis, diffuse hand swelling, synovitis, and increased ribonucleoprotein antibody. Mixed connective tissue disease has overlapping features of systemic lupus erythematosus, scleroderma, and polymyositis, and is differentiated from them by high-titer antibody to ribonucleoprotein."}
{"id": "PMID:215942", "title": "[Behavior of plasma cortisol, ACTH and STH in subjects performing controlled work on the bicycle ergometer].", "content": "A new method for the psychological and physical selection of aircrew is described. Data from the literature are cited in support of the proposition that, in muscular work tests, the response of the body to fatigue cannot only be measured by means of the usual spirometric and ECG methods, but also via the plasma cortisol, ACTH and STH response. It is shown that changes in the concentration of these hormones are mainly attributable to fatigue and its accompanying hypoglycaemia. Hitherto overlooked due to the lack of standardisation of its methods, endocrinological examination could, it is suggested, be of considerable assistance in the selection of aircrew, in the interests of greater safety in the air.", "contents": "[Behavior of plasma cortisol, ACTH and STH in subjects performing controlled work on the bicycle ergometer]. A new method for the psychological and physical selection of aircrew is described. Data from the literature are cited in support of the proposition that, in muscular work tests, the response of the body to fatigue cannot only be measured by means of the usual spirometric and ECG methods, but also via the plasma cortisol, ACTH and STH response. It is shown that changes in the concentration of these hormones are mainly attributable to fatigue and its accompanying hypoglycaemia. Hitherto overlooked due to the lack of standardisation of its methods, endocrinological examination could, it is suggested, be of considerable assistance in the selection of aircrew, in the interests of greater safety in the air."}
{"id": "PMID:215946", "title": "Peripheral and adrenal venous levels of steroids in a patient with virilizing adrenal adenoma.", "content": "The peripheral levels of 17-hydroxypregnenolone (17delta5P), progesterone (P), 17-hydroxyprogesterone (17P), testosterone (T), 5alpha-dihydrotestosterone (DHT), androstenedione (A), androst-5-ene-3beta,17beta-diol (delts5diol), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), estradiol-17beta (E2), and cortisol (F) were measured in peripheral and right adrenal venous blood of an amenorrheic patient with a right virilizing adrenal adenoma. Urinary 17-ketosteroids were markedly elevated and were not suppressed on a low dose of dexamethasone (Dex) for 7 days. Peripheral T level was 1.2 ng/ml and DHEA-S was 13,500 ng/ml. Calculations of the ratios of adrenal venous gradients for delta5 and delta4 steroids suggest that the predominant pathway of steroid secretion used by the tumor was as follows: pregnenolone (delta5P) leads to 17delta5P leads to DHEA leads to A leads to T. Following removal of the adenoma, T returned to normal levels but DHEA-S was still above normal at 4100 ng/ml. The patient became eumenorrheic with marked improvement at her hirsutism and virilization.", "contents": "Peripheral and adrenal venous levels of steroids in a patient with virilizing adrenal adenoma. The peripheral levels of 17-hydroxypregnenolone (17delta5P), progesterone (P), 17-hydroxyprogesterone (17P), testosterone (T), 5alpha-dihydrotestosterone (DHT), androstenedione (A), androst-5-ene-3beta,17beta-diol (delts5diol), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), estradiol-17beta (E2), and cortisol (F) were measured in peripheral and right adrenal venous blood of an amenorrheic patient with a right virilizing adrenal adenoma. Urinary 17-ketosteroids were markedly elevated and were not suppressed on a low dose of dexamethasone (Dex) for 7 days. Peripheral T level was 1.2 ng/ml and DHEA-S was 13,500 ng/ml. Calculations of the ratios of adrenal venous gradients for delta5 and delta4 steroids suggest that the predominant pathway of steroid secretion used by the tumor was as follows: pregnenolone (delta5P) leads to 17delta5P leads to DHEA leads to A leads to T. Following removal of the adenoma, T returned to normal levels but DHEA-S was still above normal at 4100 ng/ml. The patient became eumenorrheic with marked improvement at her hirsutism and virilization."}
{"id": "PMID:215947", "title": "Peripheral and ovarian venous concentrations of various steroid hormones in virilizing ovarian tumors.", "content": "The ovarian-peripheral gradients of various delta4 and delta5 steroids were determined for a patient with virilizing arrhenoblastoma. The high peripheral testosterone level accompanying this tumor results from increased precursor supply from both the delta4 and delta5 pathways, with the delta5 pathway predominating, and from negligible aromatase activity. A review of 45 cases of androgen-producing ovarian tumors with measurement of peripheral venous testosterone, and of 24 cases with measurement of ovarian venous testosterone, and a comparison with findings in 159 patients with hirsutism of functional origin reveal the following 1) An androgen-producing tumor must be ruled out when peripheral testosterone exceeds 2 ng/ml; 2) an ovarian venous testosterone level exceeding 20 ng/ml generally accompanies a tumor, particularly when the tumor is less than 5 cm in diameter; and 3) virtually all (98%) of the tumors reviewed were accompanied by virilization, regardless of the peripheral concentration of testosterone.", "contents": "Peripheral and ovarian venous concentrations of various steroid hormones in virilizing ovarian tumors. The ovarian-peripheral gradients of various delta4 and delta5 steroids were determined for a patient with virilizing arrhenoblastoma. The high peripheral testosterone level accompanying this tumor results from increased precursor supply from both the delta4 and delta5 pathways, with the delta5 pathway predominating, and from negligible aromatase activity. A review of 45 cases of androgen-producing ovarian tumors with measurement of peripheral venous testosterone, and of 24 cases with measurement of ovarian venous testosterone, and a comparison with findings in 159 patients with hirsutism of functional origin reveal the following 1) An androgen-producing tumor must be ruled out when peripheral testosterone exceeds 2 ng/ml; 2) an ovarian venous testosterone level exceeding 20 ng/ml generally accompanies a tumor, particularly when the tumor is less than 5 cm in diameter; and 3) virtually all (98%) of the tumors reviewed were accompanied by virilization, regardless of the peripheral concentration of testosterone."}
{"id": "PMID:215948", "title": "[IgA-immunoglobulins and HLA-A1 antigen in Wilms' tumor. Significance for the prognosis of the disease].", "content": "In 45 patients with Wilms' tumor of the kidney the IgG, IgA, and IgM serum immunoglobulin levels were quantitated and 23 antigens of HLA-A and HLA-B locues were typed on the same patients' lymphocytes. In 22 individuals with increased IgA immunoglobulin level a more frequent incidence of HLA-A 1 antigen was found. This antigen was established in 62.5% of patients with IgA levels higher than 200 IU/ml. Considering the fact that 86.35% of the patients survive two years, and 16 of 22 patients (= 72.72%) are practically cured, it is suggested that the simultaneous occurrence of increased levels of IgA immunoglobulin and of HLA antigen A 1, is a favourable prognostic sign.", "contents": "[IgA-immunoglobulins and HLA-A1 antigen in Wilms' tumor. Significance for the prognosis of the disease]. In 45 patients with Wilms' tumor of the kidney the IgG, IgA, and IgM serum immunoglobulin levels were quantitated and 23 antigens of HLA-A and HLA-B locues were typed on the same patients' lymphocytes. In 22 individuals with increased IgA immunoglobulin level a more frequent incidence of HLA-A 1 antigen was found. This antigen was established in 62.5% of patients with IgA levels higher than 200 IU/ml. Considering the fact that 86.35% of the patients survive two years, and 16 of 22 patients (= 72.72%) are practically cured, it is suggested that the simultaneous occurrence of increased levels of IgA immunoglobulin and of HLA antigen A 1, is a favourable prognostic sign."}
{"id": "PMID:215949", "title": "[Collagenolytic activity of cervix carcinoma].", "content": "We estimated collagenolytic activity of 10 invasive carcinomas of the cervix by means of a biological assay. Collagenolysis was found in 7 specimens. In order to detect the origin of the collagenolytic enzyme additional inhibition studies with ethylendiaminetetraacetate and normal human serum were performed. Normal human serum inhibited the enzymatic process by a mean percentage of 14.9%, EDTA up to 9.1%. D-penicillamine and 1.10-o-phenanthroline which inhibit collagenase specifically stopped the enzymatic activity of the tumor completely. According to our results it can be suggested that the collagenolytic activity of carcinoma of the cervix uteri is not derived from serum or from polymorphonuclear cells but is created by the tumor itself.", "contents": "[Collagenolytic activity of cervix carcinoma]. We estimated collagenolytic activity of 10 invasive carcinomas of the cervix by means of a biological assay. Collagenolysis was found in 7 specimens. In order to detect the origin of the collagenolytic enzyme additional inhibition studies with ethylendiaminetetraacetate and normal human serum were performed. Normal human serum inhibited the enzymatic process by a mean percentage of 14.9%, EDTA up to 9.1%. D-penicillamine and 1.10-o-phenanthroline which inhibit collagenase specifically stopped the enzymatic activity of the tumor completely. According to our results it can be suggested that the collagenolytic activity of carcinoma of the cervix uteri is not derived from serum or from polymorphonuclear cells but is created by the tumor itself."}
{"id": "PMID:215950", "title": "[Ratio of cyclo-3':5'-adenosinemonophosphate to cyclo-3':5'-guanosine-monophosphate in human tumor tissue].", "content": "In human tumor tissues of different degrees of differentiation--nevus-cell-nevus, basalioma, malign melanoma--the cAMP and cGMP content was determined and compared with the corresponding normal values. It is demonstrated that the quotient of the cAMP to the cGMP values is of importance rather than the latter values for themselves. For the benign tumor, this quotient differs only slightly from that of the adjacent normal, sound tissue. On the other hand, for the two malign tumors a drastic decrease of the quotient as compared to that of the normal tissue was found to occur.", "contents": "[Ratio of cyclo-3':5'-adenosinemonophosphate to cyclo-3':5'-guanosine-monophosphate in human tumor tissue]. In human tumor tissues of different degrees of differentiation--nevus-cell-nevus, basalioma, malign melanoma--the cAMP and cGMP content was determined and compared with the corresponding normal values. It is demonstrated that the quotient of the cAMP to the cGMP values is of importance rather than the latter values for themselves. For the benign tumor, this quotient differs only slightly from that of the adjacent normal, sound tissue. On the other hand, for the two malign tumors a drastic decrease of the quotient as compared to that of the normal tissue was found to occur."}
{"id": "PMID:215953", "title": "Ultrastructural studies of intraoral verruca vulgaris.", "content": "The literature offers conflicting views regarding the existence of verruca vulgaris in the oral cavity. In an attempt to clarify this issue, a series of ten oral lesions which had been diagnosed as verruca vulgaris and ten oral lesions diagnosed as squamous-cell papilloma were examined ultrastructurally. Six of the lesions diagnosed as verruca vulgaris contained the characteristic intranuclear viral particles which are normally found in that lesion. None of the lesions diagnosed as squamous-cell papilloma exhibited this type of intranuclear viral inclusions.", "contents": "Ultrastructural studies of intraoral verruca vulgaris. The literature offers conflicting views regarding the existence of verruca vulgaris in the oral cavity. In an attempt to clarify this issue, a series of ten oral lesions which had been diagnosed as verruca vulgaris and ten oral lesions diagnosed as squamous-cell papilloma were examined ultrastructurally. Six of the lesions diagnosed as verruca vulgaris contained the characteristic intranuclear viral particles which are normally found in that lesion. None of the lesions diagnosed as squamous-cell papilloma exhibited this type of intranuclear viral inclusions."}
{"id": "PMID:215959", "title": "Asymptomatic viral hepatitis types A and B in an adolescent population.", "content": "Sera from 95 adolescents were examined for markers of hepatitis B virus (HBV) infection and hepatitis A virus (HAV) infection. HBV markers were found in eight adolescents (8%) and evidence of previous HAV infection was found in 18 adolescents (19%); none had a history of clinically recognizable hepatitis. These findings support the growing evidence that HBV and HAV infections are diseases of the pediatric age group, and that testing of HBV vaccines when they become available for patient use will have to include a pediatric population.", "contents": "Asymptomatic viral hepatitis types A and B in an adolescent population. Sera from 95 adolescents were examined for markers of hepatitis B virus (HBV) infection and hepatitis A virus (HAV) infection. HBV markers were found in eight adolescents (8%) and evidence of previous HAV infection was found in 18 adolescents (19%); none had a history of clinically recognizable hepatitis. These findings support the growing evidence that HBV and HAV infections are diseases of the pediatric age group, and that testing of HBV vaccines when they become available for patient use will have to include a pediatric population."}
{"id": "PMID:215965", "title": "Acid hydrolase activity in red and white skeletal muscle of mice during a two-week period following exhausting exercise.", "content": "The activities of beta-glucuronidase, beta-N-acetylglucosaminidase, arylsulphatase, ribonuclease, p-nitrophenylphosphatase, and malate dehydrogenase together with protein content were assayed from representative mixed (m. rectus femoris), predominantly red (proximal heads of m. vastus lateralis, m.v. medius and m. v. intermedius), and predominantly white (distal head of m. vastus lateralis) muscle homogenates of mice during a two-week period following one single exposure to exhausting intermittent running on a treadmill. The activities of cathepsin D and beta-glycerophosphatase were assayed from mixed muscle only. In all three muscle types, particularly in red muscle, the activities of beta-glucuronidase, beta-N-acetylglucosaminidase, arylsulphatase, and ribonuclease progressively increased between one to five days after the exercise; thereafter the activities began to decrease, being near the conrol values 15 days after the exercise. In mixed muscle, cathepsin D activity increased. No corresponding changes were observed in the activities of acid phosphatases. The time course of the activity changes closely resembled that earlier found to be caused by ischaemia in rabbit muscles. It is tentatively concluded that the two treatments, exhaustive exercise and temporary ischaemia, cause similar cell injuries, and that the lysosomal system involved seems to function similarly in the post-stress recovery of the fibres from these injuries.", "contents": "Acid hydrolase activity in red and white skeletal muscle of mice during a two-week period following exhausting exercise. The activities of beta-glucuronidase, beta-N-acetylglucosaminidase, arylsulphatase, ribonuclease, p-nitrophenylphosphatase, and malate dehydrogenase together with protein content were assayed from representative mixed (m. rectus femoris), predominantly red (proximal heads of m. vastus lateralis, m.v. medius and m. v. intermedius), and predominantly white (distal head of m. vastus lateralis) muscle homogenates of mice during a two-week period following one single exposure to exhausting intermittent running on a treadmill. The activities of cathepsin D and beta-glycerophosphatase were assayed from mixed muscle only. In all three muscle types, particularly in red muscle, the activities of beta-glucuronidase, beta-N-acetylglucosaminidase, arylsulphatase, and ribonuclease progressively increased between one to five days after the exercise; thereafter the activities began to decrease, being near the conrol values 15 days after the exercise. In mixed muscle, cathepsin D activity increased. No corresponding changes were observed in the activities of acid phosphatases. The time course of the activity changes closely resembled that earlier found to be caused by ischaemia in rabbit muscles. It is tentatively concluded that the two treatments, exhaustive exercise and temporary ischaemia, cause similar cell injuries, and that the lysosomal system involved seems to function similarly in the post-stress recovery of the fibres from these injuries."}
{"id": "PMID:215969", "title": "[Epstein-Barr virus and infectious mononucleosis. A clinical study of Epstein-Barr antibodies (author's transl)].", "content": "Thirty-seven patients--aged 2 to 58--with clinical and hematological signs of infectious mononucleosis were studied. Thirty patients gave serologic evidence of Epstein-Barr virus infections; antibodies to viral capsid antigen (VCA) appeared very early (only two seroconversions and 4 cases of increased titer were detected); antibodies to early antigen (EA) occured in 25 patients, but only 9 had high titers; antibodies to nuclear antigen (EBNA) appeared late in the course of the disease. VCA-specific IgM antibodies occurred in 25 cases (they usually disappeared during the 2nd month). The transforming EB virus was found in the saliva of the 2 patients where we looked for it. Heterophile antibody responses occured in only 17 patients; among children about half of them had a positive Paul-Bunnell-Davidsohn test. After the age of 40 (3 cases) heterophile antibodies were no longer found. Three patients had another recent viral infection at the same time as the primary EBV infection (two cases of rubella, one case of adenovirus infection). Of the remaining 7 patients (having either no antibodies to EBV or antibodies of past infection), 2 had cytomegalovirus infections and one rubella.", "contents": "[Epstein-Barr virus and infectious mononucleosis. A clinical study of Epstein-Barr antibodies (author's transl)]. Thirty-seven patients--aged 2 to 58--with clinical and hematological signs of infectious mononucleosis were studied. Thirty patients gave serologic evidence of Epstein-Barr virus infections; antibodies to viral capsid antigen (VCA) appeared very early (only two seroconversions and 4 cases of increased titer were detected); antibodies to early antigen (EA) occured in 25 patients, but only 9 had high titers; antibodies to nuclear antigen (EBNA) appeared late in the course of the disease. VCA-specific IgM antibodies occurred in 25 cases (they usually disappeared during the 2nd month). The transforming EB virus was found in the saliva of the 2 patients where we looked for it. Heterophile antibody responses occured in only 17 patients; among children about half of them had a positive Paul-Bunnell-Davidsohn test. After the age of 40 (3 cases) heterophile antibodies were no longer found. Three patients had another recent viral infection at the same time as the primary EBV infection (two cases of rubella, one case of adenovirus infection). Of the remaining 7 patients (having either no antibodies to EBV or antibodies of past infection), 2 had cytomegalovirus infections and one rubella."}
{"id": "PMID:215972", "title": "Mental health patient assessment record: interobserver reliability.", "content": "To determine interobserver reliability of the Mental Health Patient Assessment Record, two independent observers, a visiting nurse and the investigator who was a constant second observer throughout the study, made home visit observations at two specified times: the initial assessment (time I), and approximately two months later (time II). The stratified random sample consisted of 26 discharged psychiatric patients who comprised approximately 75 percent of the new admissions to the agency during a four-week period. At time I, 26 visits were completed and values were obtained, using the Pearson product moment correlation for the scores on the MHPAR: 1) overall behavior, r = .96; 2) physical behavior, r = .91; 3) psychological behavior, r = .93; 4) social behavior, r = .83; and 5) medical behavior, r = .98. The sign test applied to total and category scores revealed that only one category, social behaviors, demonstrated a significant systematic bias of the constant second observer. Of the 26 patients observed at time I, 20 were visited at time II. The following values were obtained using the Pearson product moment correlation for MHPAR scores: 1) overall behavior, r = .98; 2) physical behavior, r = .91; 3) psychological behavior, r = .91; 4) social behavior, r = .94; and 5) medical behavior, r = .99. The sign test applied to total and category scores showed no systematic bias of the constant second observer.", "contents": "Mental health patient assessment record: interobserver reliability. To determine interobserver reliability of the Mental Health Patient Assessment Record, two independent observers, a visiting nurse and the investigator who was a constant second observer throughout the study, made home visit observations at two specified times: the initial assessment (time I), and approximately two months later (time II). The stratified random sample consisted of 26 discharged psychiatric patients who comprised approximately 75 percent of the new admissions to the agency during a four-week period. At time I, 26 visits were completed and values were obtained, using the Pearson product moment correlation for the scores on the MHPAR: 1) overall behavior, r = .96; 2) physical behavior, r = .91; 3) psychological behavior, r = .93; 4) social behavior, r = .83; and 5) medical behavior, r = .98. The sign test applied to total and category scores revealed that only one category, social behaviors, demonstrated a significant systematic bias of the constant second observer. Of the 26 patients observed at time I, 20 were visited at time II. The following values were obtained using the Pearson product moment correlation for MHPAR scores: 1) overall behavior, r = .98; 2) physical behavior, r = .91; 3) psychological behavior, r = .91; 4) social behavior, r = .94; and 5) medical behavior, r = .99. The sign test applied to total and category scores showed no systematic bias of the constant second observer."}
{"id": "PMID:215975", "title": "Fibrous histiocytoma: a histological and statistical analysis of 155 cases.", "content": "Various salient histological features were rated from + to +++ in a semiquantitative evaluation of a series of 155 cases of fibrous histiocytoma. Relations between individual histological features, as well as between histological findings, localisation and size of lesions, and age or sex of the patient were tested statistically. Most impressive was an inverse proportional relationship between cellular and fibrillar densities: highly cellular fibrous histiocytomas chiefly showed little fiber formation. Accordingly, cases with marked fiber formation were distinguished by low cellularity. Based on this statistically significant relation, 3 subtypes could be classified on a scale of increasing fiber formation and decreasing cellular density. The majority of cases showed medium cellularity and fibrillar density, with distinct storiform (spokewheel or \"whirlygig\") pattern which is compatible with typical storiform histocytoma, including clincally progressive, recurrant FH and/or \"dermatofibrosarcoma protuberans\". The typical patient was more frequently female than male, 40 years of age with a 0.5 to 1.0 cm size tumor node in the lower extremities located in the corium, often with beginning infiltration of the subcutaneous fat tissue.", "contents": "Fibrous histiocytoma: a histological and statistical analysis of 155 cases. Various salient histological features were rated from + to +++ in a semiquantitative evaluation of a series of 155 cases of fibrous histiocytoma. Relations between individual histological features, as well as between histological findings, localisation and size of lesions, and age or sex of the patient were tested statistically. Most impressive was an inverse proportional relationship between cellular and fibrillar densities: highly cellular fibrous histiocytomas chiefly showed little fiber formation. Accordingly, cases with marked fiber formation were distinguished by low cellularity. Based on this statistically significant relation, 3 subtypes could be classified on a scale of increasing fiber formation and decreasing cellular density. The majority of cases showed medium cellularity and fibrillar density, with distinct storiform (spokewheel or \"whirlygig\") pattern which is compatible with typical storiform histocytoma, including clincally progressive, recurrant FH and/or \"dermatofibrosarcoma protuberans\". The typical patient was more frequently female than male, 40 years of age with a 0.5 to 1.0 cm size tumor node in the lower extremities located in the corium, often with beginning infiltration of the subcutaneous fat tissue."}
{"id": "PMID:215976", "title": "Infectious mononucleosis and Epstein-Barr virus. 1. Epidemiology, pathogenesis, immune response.", "content": "The evidence linking Epstein-Barr virus causally with infectious mononucleosis is compelling. The disease occurs only in persons who lack antibody to this virus, and serologic findings during the acute illness provide almost certain evidence for its etiologic association. Additional evidence is derived from transformation studies using lymphocytes from persons infected with Epstein-Barr virus. Epidemiologic studies have related the need for close contact with salivary secretions to the low communicability of infectious mononucleosis. The clinically relevant antibodies which develop during the disease, other than heterophile antibody, are those against the viral capsid antigen. Part 2 of this article considers the clinical picture, diagnosis, and management and begins on page 95.", "contents": "Infectious mononucleosis and Epstein-Barr virus. 1. Epidemiology, pathogenesis, immune response. The evidence linking Epstein-Barr virus causally with infectious mononucleosis is compelling. The disease occurs only in persons who lack antibody to this virus, and serologic findings during the acute illness provide almost certain evidence for its etiologic association. Additional evidence is derived from transformation studies using lymphocytes from persons infected with Epstein-Barr virus. Epidemiologic studies have related the need for close contact with salivary secretions to the low communicability of infectious mononucleosis. The clinically relevant antibodies which develop during the disease, other than heterophile antibody, are those against the viral capsid antigen. Part 2 of this article considers the clinical picture, diagnosis, and management and begins on page 95."}
{"id": "PMID:215977", "title": "Infectious mononucleosis and Epstein-Barr virus. 2. Clinical picture, diagnosis, management.", "content": "The diagnosis of infectious mononucleosis is confirmed by hematologic, biochemical, and serologic data. An absolute increase in peripheral mononuclear cells to at least 4,500/cu mm is an essential feature. The serologic hallmark of the disease is the presence of heterophile antibody. The age of the patient may affect the clinical presentation and laboratory findings. Therapy is largely supportive, with steroids being used only in the presence of certain severe complications.", "contents": "Infectious mononucleosis and Epstein-Barr virus. 2. Clinical picture, diagnosis, management. The diagnosis of infectious mononucleosis is confirmed by hematologic, biochemical, and serologic data. An absolute increase in peripheral mononuclear cells to at least 4,500/cu mm is an essential feature. The serologic hallmark of the disease is the presence of heterophile antibody. The age of the patient may affect the clinical presentation and laboratory findings. Therapy is largely supportive, with steroids being used only in the presence of certain severe complications."}
{"id": "PMID:215978", "title": "Pathophysiology of lipid transport disorders.", "content": "Over the past decade considerable insight into the mechanisms involved in normal and abnormal transport as well as the mode of action of hypolipidaemic drugs has been achieved. This progress has made the approach to the hyperlipidaemic patient increasingly more precise and effective.", "contents": "Pathophysiology of lipid transport disorders. Over the past decade considerable insight into the mechanisms involved in normal and abnormal transport as well as the mode of action of hypolipidaemic drugs has been achieved. This progress has made the approach to the hyperlipidaemic patient increasingly more precise and effective."}
{"id": "PMID:215979", "title": "Inheritance of endogenous hypertriglyceridaemia type IIB or IV.", "content": "The genetic background of endogenous hypertriglyceridaemia was evaluated in 239 first-degree relatives of 48 probands with serum triglyceride level in excess of 30.0 mM and with either normal (type IV) or elevated (type IIB) serum cholesterol concentration. In one quarter of the families, all examined first-degree relatives of the proband were normolipidaemic and, thus, the disorder was classified as non-genetic. Nine of 26 probands with IV in contrast to only three of 22 probands with type IIB abnormality fell into this category. In 75% of the families the hyperlipoproteinaemia was caused by one or several abnormal genes. A multiple-type (combined) familial hyperlipidaemia could be demonstrated in 30 families and a single-type IIB or IV familial disease was found in 6 instances. Thus, the multiple-type hyperlipoproteinaemia seems to be responsible for the elevated serum triglyceride level in more than one-half of the cases with moderate to severe hyperglyceridaemia while a pure familial endogenous hypertriglyceridaemia is relatively rare. Exactly 50% of the members of families with the multiple-type lipid disorder were affected but the distribution of individual cholesterol and triglycerides values did not show a definite bimodality. It is possible that the abnormality is heterogeneous and includes several disease entities, which are indistinguishable by a conventional lipid or lipoprotein analysis but can be separated by kinetic or enzyme  studies.", "contents": "Inheritance of endogenous hypertriglyceridaemia type IIB or IV. The genetic background of endogenous hypertriglyceridaemia was evaluated in 239 first-degree relatives of 48 probands with serum triglyceride level in excess of 30.0 mM and with either normal (type IV) or elevated (type IIB) serum cholesterol concentration. In one quarter of the families, all examined first-degree relatives of the proband were normolipidaemic and, thus, the disorder was classified as non-genetic. Nine of 26 probands with IV in contrast to only three of 22 probands with type IIB abnormality fell into this category. In 75% of the families the hyperlipoproteinaemia was caused by one or several abnormal genes. A multiple-type (combined) familial hyperlipidaemia could be demonstrated in 30 families and a single-type IIB or IV familial disease was found in 6 instances. Thus, the multiple-type hyperlipoproteinaemia seems to be responsible for the elevated serum triglyceride level in more than one-half of the cases with moderate to severe hyperglyceridaemia while a pure familial endogenous hypertriglyceridaemia is relatively rare. Exactly 50% of the members of families with the multiple-type lipid disorder were affected but the distribution of individual cholesterol and triglycerides values did not show a definite bimodality. It is possible that the abnormality is heterogeneous and includes several disease entities, which are indistinguishable by a conventional lipid or lipoprotein analysis but can be separated by kinetic or enzyme  studies."}
{"id": "PMID:215980", "title": "Serum lipoprotein abnormalities in ischaemic heart disease.", "content": "Quantitative lipoprotein level data was obtained from healthy subjects and patients with ischaemic heart disease or peripheral vascular disease in four European communities. Hypertriglyceridaemia, due mainly to an increase in VLDL triglyceride, was commoner in London and Uppsala than in Naples and Geneva. In three communities there were significant increases in total serum cholesterol due to both increases in LDL and in VLDL cholesterol. Hypercholesterolaemic and hypertriglyceridaemic status were over-represented in both ischaemic heart disease and peripheral vascular disease patients.", "contents": "Serum lipoprotein abnormalities in ischaemic heart disease. Quantitative lipoprotein level data was obtained from healthy subjects and patients with ischaemic heart disease or peripheral vascular disease in four European communities. Hypertriglyceridaemia, due mainly to an increase in VLDL triglyceride, was commoner in London and Uppsala than in Naples and Geneva. In three communities there were significant increases in total serum cholesterol due to both increases in LDL and in VLDL cholesterol. Hypercholesterolaemic and hypertriglyceridaemic status were over-represented in both ischaemic heart disease and peripheral vascular disease patients."}
{"id": "PMID:215981", "title": "Effects of dietary treatment on lipoprotein levels in hyperlipoproteinaemia.", "content": "Diet constitutes the basis of all lipid lowering therapy. The mechanisms responsible for the effects of the different dietary measures are not yet fully understood. Dietary treatment 'normalized' the lipid levels in over 50% of the mild to moderate hyperlipoproteinaemic states encountered in a middle-aged population with clinical manifestations of atherosclerotic cardiovascular disease. Triglyceride and cholesterol determinations in isolated lipoprotein fractions supplied additional information on the character and extent of the lipoprotein changes induced by diet.", "contents": "Effects of dietary treatment on lipoprotein levels in hyperlipoproteinaemia. Diet constitutes the basis of all lipid lowering therapy. The mechanisms responsible for the effects of the different dietary measures are not yet fully understood. Dietary treatment 'normalized' the lipid levels in over 50% of the mild to moderate hyperlipoproteinaemic states encountered in a middle-aged population with clinical manifestations of atherosclerotic cardiovascular disease. Triglyceride and cholesterol determinations in isolated lipoprotein fractions supplied additional information on the character and extent of the lipoprotein changes induced by diet."}
{"id": "PMID:215984", "title": "The prevalence of hyperlipoproteinaemia in vascular disease.", "content": "Surveys of the apparently healthy working population of the West of Scotland have revealed a high prevalence of hyperlipoproteinaemia (HIP). In males, type IV occurred more frequently (12%) than in females (3.3%), although obesity played an important part in this finding. HLP also occurred frequently (61%) in survivors of myocardial infarction (type II 39%, type IV 22%) but less frequently in peripheral vascular disease (38%), although there was a higher prevalence in females (47%) than males (32%) largely due to an increased prevalence of type IIa (29.5% cf 7.5%). HLP did not appear to play a significant role in cerebrovascular disease.", "contents": "The prevalence of hyperlipoproteinaemia in vascular disease. Surveys of the apparently healthy working population of the West of Scotland have revealed a high prevalence of hyperlipoproteinaemia (HIP). In males, type IV occurred more frequently (12%) than in females (3.3%), although obesity played an important part in this finding. HLP also occurred frequently (61%) in survivors of myocardial infarction (type II 39%, type IV 22%) but less frequently in peripheral vascular disease (38%), although there was a higher prevalence in females (47%) than males (32%) largely due to an increased prevalence of type IIa (29.5% cf 7.5%). HLP did not appear to play a significant role in cerebrovascular disease."}
{"id": "PMID:215985", "title": "Treatment of severe and mild hypercholesterolaemia with probucol and neomycin.", "content": "Administration of probucol to 23 patients with familial xanthomatotic hypercholesterolaemia reduced the serum cholesterol level during the 9-month study by 9%, while in 15 patients with less severe hypercholesterolaemia the decrease was on an average 15%. A reduction of more than 10% was obtained in 57% of the former and 80% of the latter subjects. In a double blind trial a greater reduction was obtained in serum cholesterol by probucol than by placebo. Neomycin lowered the serum cholesterol more effectively than probucol in subjects with severe type II abnormality and was at least equally effective in less severe type II patients. Probucol increased transiently the faecal bile acid and dietary cholesterol excretion, while neomycin enhanced the faecal elimination of cholesterol as neutral sterols.", "contents": "Treatment of severe and mild hypercholesterolaemia with probucol and neomycin. Administration of probucol to 23 patients with familial xanthomatotic hypercholesterolaemia reduced the serum cholesterol level during the 9-month study by 9%, while in 15 patients with less severe hypercholesterolaemia the decrease was on an average 15%. A reduction of more than 10% was obtained in 57% of the former and 80% of the latter subjects. In a double blind trial a greater reduction was obtained in serum cholesterol by probucol than by placebo. Neomycin lowered the serum cholesterol more effectively than probucol in subjects with severe type II abnormality and was at least equally effective in less severe type II patients. Probucol increased transiently the faecal bile acid and dietary cholesterol excretion, while neomycin enhanced the faecal elimination of cholesterol as neutral sterols."}
{"id": "PMID:215986", "title": "Cholestyramine, clofibrate and nicotinic acid as single or combined treatment of type IIa and IIb hyperlipoproteinaemia.", "content": "1. In type IIa and IIb hyperlipoproteinaemia, treatment with 16 g cholestyramine daily reduced the cholesterol concentration 23%. By adding clofibrate this effect was enhanced to a 29% reduction and at the same time clofibrate reduced the triglyceride (TG) concentration 33%. 2. The optimal cholesterol reduction with clofibrate in type II was 17% and was found after treatment with 1.5 g clofibrate/day. The optimal TG reduction appeared to be achieved with a daily dose of 2 g.3. Nicotinic acid in the form of niceritrol had another type of dose-response in type II with doses from 3 to 6 g/day. It appeared as if the optimal dose probably was above 6 g daily. The 6 g dose produced a cholesterol reduction of 22% and in type IIb there was at the same time a 50% reduction of the TG concentration. 4. By combining 3 g niceritrol with 2 g clofibrate almost the same effect on serum lipids was obtained as with 6 g niceritrol. When choosing a drug for treatment of hyperlipoproteinaemia it is necessary to consider not only the lipid lowering effect but also the side effects which are not discussed here. By combining clofibrate with either cholestyramine or niceritrol it was possible to improve the lipid lowering effect. There were no side effects which were not seen when the drugs were used alone. A more frequent use of combinations to improve the treatment of hyperlipoproteinaemia is recommended.", "contents": "Cholestyramine, clofibrate and nicotinic acid as single or combined treatment of type IIa and IIb hyperlipoproteinaemia. 1. In type IIa and IIb hyperlipoproteinaemia, treatment with 16 g cholestyramine daily reduced the cholesterol concentration 23%. By adding clofibrate this effect was enhanced to a 29% reduction and at the same time clofibrate reduced the triglyceride (TG) concentration 33%. 2. The optimal cholesterol reduction with clofibrate in type II was 17% and was found after treatment with 1.5 g clofibrate/day. The optimal TG reduction appeared to be achieved with a daily dose of 2 g.3. Nicotinic acid in the form of niceritrol had another type of dose-response in type II with doses from 3 to 6 g/day. It appeared as if the optimal dose probably was above 6 g daily. The 6 g dose produced a cholesterol reduction of 22% and in type IIb there was at the same time a 50% reduction of the TG concentration. 4. By combining 3 g niceritrol with 2 g clofibrate almost the same effect on serum lipids was obtained as with 6 g niceritrol. When choosing a drug for treatment of hyperlipoproteinaemia it is necessary to consider not only the lipid lowering effect but also the side effects which are not discussed here. By combining clofibrate with either cholestyramine or niceritrol it was possible to improve the lipid lowering effect. There were no side effects which were not seen when the drugs were used alone. A more frequent use of combinations to improve the treatment of hyperlipoproteinaemia is recommended."}
{"id": "PMID:215988", "title": "Neonatal diagnosis of Fredrickson type II hyperlipoproteinaemia.", "content": "Cord-serum beta-lipoprotein was measured by an immunological method in 303 children. The blood lipids were studied at 7-9 and 14-19 months after birth. The lipids of both parents were measured. Six children were found to have a greater than 2 SD elevation of beta-lipoprotein at birth. Three of these had hypertriglyceridaemia and 3 had type II hyperlipoproteinaemia. The rapid and quantitative measurement of beta-lipoprotein looks promising for screening of type II hyperlipoproteinaemia at birth.", "contents": "Neonatal diagnosis of Fredrickson type II hyperlipoproteinaemia. Cord-serum beta-lipoprotein was measured by an immunological method in 303 children. The blood lipids were studied at 7-9 and 14-19 months after birth. The lipids of both parents were measured. Six children were found to have a greater than 2 SD elevation of beta-lipoprotein at birth. Three of these had hypertriglyceridaemia and 3 had type II hyperlipoproteinaemia. The rapid and quantitative measurement of beta-lipoprotein looks promising for screening of type II hyperlipoproteinaemia at birth."}
{"id": "PMID:215990", "title": "Cyclical release of vasoactive intestinal polypeptide (VIP) from a pancreatic islet cell apudoma.", "content": "A patient is described who presented with the classical symptomatology and profound electrolyte disturbance of the Verner-Morrison syndrome due to a pancreatic apudoma secreting vasoactive intestinal polypeptide (VIP). Diagnosis was confirmed by plasma VIP as measured by a radio-immunoassay technique now available. It is suggested that the cyclical nature of the symptoms in this case was due to cyclical release of VIP from the tumour in response to an unknown stimulus. Perfusion studies confirmed the excess secretory state of water, sodium and chloride in the small intestine. Symptoms were completely abolished by surgery and the progress is being monitored by means of serial plasma VIP estimations to detect any early recurrence of metastatic disease.", "contents": "Cyclical release of vasoactive intestinal polypeptide (VIP) from a pancreatic islet cell apudoma. A patient is described who presented with the classical symptomatology and profound electrolyte disturbance of the Verner-Morrison syndrome due to a pancreatic apudoma secreting vasoactive intestinal polypeptide (VIP). Diagnosis was confirmed by plasma VIP as measured by a radio-immunoassay technique now available. It is suggested that the cyclical nature of the symptoms in this case was due to cyclical release of VIP from the tumour in response to an unknown stimulus. Perfusion studies confirmed the excess secretory state of water, sodium and chloride in the small intestine. Symptoms were completely abolished by surgery and the progress is being monitored by means of serial plasma VIP estimations to detect any early recurrence of metastatic disease."}
{"id": "PMID:215996", "title": "Epidermal growth factor: biological activity requires persistent occupation of high-affinity cell surface receptors.", "content": "The enhancement of DNA synthesis by epidermal growth factor (EGF) in cultured human fibroblasts is demonstrable 24 hr after incubation of the cells at 37 degrees C with very low concentrations (0.83 nM) of the hormone for very short periods (30 min) followed by thorough washing of the cells to remove the free hormone in the medium. This effect must result from persistent, extraordinarily tight binding of the hormone to surface receptors, because the addition of specific, purified anti-EGF IgG as late as 8 hr after initial hormone exposure can completely reverse the biological effects of the hormone. This causes only a slight (but significant) increase in the rate of dissociation at 37 degrees C of the cell-bound (125)I-labeled EGF at low occupancy. Together with the fact that in the presence or absence of antibody virtually all of the demonstrable cell-bound (125)I-labeled EGF can be shown to dissociate from the cell during a period as short as 2-3 hr, the data suggest the possibility that the biological effects of this hormone may be mediated by occupation of only a negligible fraction of very high affinity binding sites. Thus, the processes of hormone internalization, degradation, and \"down regulation\" may be irrelevant to the effects of the hormone on DNA synthesis. For this effect the crucial and limiting processes appear to be strictly related to the continuous and persistent occupation of cell surface receptors.", "contents": "Epidermal growth factor: biological activity requires persistent occupation of high-affinity cell surface receptors. The enhancement of DNA synthesis by epidermal growth factor (EGF) in cultured human fibroblasts is demonstrable 24 hr after incubation of the cells at 37 degrees C with very low concentrations (0.83 nM) of the hormone for very short periods (30 min) followed by thorough washing of the cells to remove the free hormone in the medium. This effect must result from persistent, extraordinarily tight binding of the hormone to surface receptors, because the addition of specific, purified anti-EGF IgG as late as 8 hr after initial hormone exposure can completely reverse the biological effects of the hormone. This causes only a slight (but significant) increase in the rate of dissociation at 37 degrees C of the cell-bound (125)I-labeled EGF at low occupancy. Together with the fact that in the presence or absence of antibody virtually all of the demonstrable cell-bound (125)I-labeled EGF can be shown to dissociate from the cell during a period as short as 2-3 hr, the data suggest the possibility that the biological effects of this hormone may be mediated by occupation of only a negligible fraction of very high affinity binding sites. Thus, the processes of hormone internalization, degradation, and \"down regulation\" may be irrelevant to the effects of the hormone on DNA synthesis. For this effect the crucial and limiting processes appear to be strictly related to the continuous and persistent occupation of cell surface receptors."}
{"id": "PMID:215997", "title": "Cell-free synthesis and processing of the proteins of poliovirus.", "content": "Poliovirus RNA can be translated completely and accurately in rabbit reticulocyte lysates; the nascent poly-protein is processed to give primary products 1a, X, and 1b indistinguishable from those made in poliovirus-infected HeLa cells. The capsid precursor protein 1a is processed to form the capsid proteins VP0, VP1, and VP3, while the noncapsid precursor 1b is processed to form protein 2.", "contents": "Cell-free synthesis and processing of the proteins of poliovirus. Poliovirus RNA can be translated completely and accurately in rabbit reticulocyte lysates; the nascent poly-protein is processed to give primary products 1a, X, and 1b indistinguishable from those made in poliovirus-infected HeLa cells. The capsid precursor protein 1a is processed to form the capsid proteins VP0, VP1, and VP3, while the noncapsid precursor 1b is processed to form protein 2."}
{"id": "PMID:215998", "title": "Recombination between viral and cellular sequences generates transforming sarcoma virus.", "content": "A series of sarcoma viruses has been obtained from tumors induced by transformation-defective (td) mutants of the Schmidt-Ruppin strain of Rous sarcoma virus, subgroup A (SR-A). The RNA sequences of these \"recovered avian sarcoma viruses\" (rASVs) were compared with those of td mutants and of SR-A by oligonucleotide fingerprinting. Of six sarcoma-specific oligonucleotides present in SR-A RNA, three to six were missing in the RNAs of the four td mutants examined. All six isolates of rASV examined have regained these six oligonucleotides. In addition, most rASV RNAs have three new oligonucleotides not present in the RNA either of td mutants or of SR-A. The newly obtained oligonucleotides are located between 800 and 2600 nucleotides from the 3' end of rASV RNA, which corresponds to the src region of SR-A RNA mapped previously. Furthermore, viral RNAs of two td mutants isolated from a clone of rASV lack most src-specific oligonucleotides, including the three new ones. No differences were found among RNAs of td, SR-A, and rASV in the regions outside of src. Our results indicate that RNA sequences that rASVs have acquired from cells in the process of conversion from td virus to transforming virus are mapped within the src region and segregate with the transforming function. Some of the sequences are new and some are identical with those in SR-A RNA.", "contents": "Recombination between viral and cellular sequences generates transforming sarcoma virus. A series of sarcoma viruses has been obtained from tumors induced by transformation-defective (td) mutants of the Schmidt-Ruppin strain of Rous sarcoma virus, subgroup A (SR-A). The RNA sequences of these \"recovered avian sarcoma viruses\" (rASVs) were compared with those of td mutants and of SR-A by oligonucleotide fingerprinting. Of six sarcoma-specific oligonucleotides present in SR-A RNA, three to six were missing in the RNAs of the four td mutants examined. All six isolates of rASV examined have regained these six oligonucleotides. In addition, most rASV RNAs have three new oligonucleotides not present in the RNA either of td mutants or of SR-A. The newly obtained oligonucleotides are located between 800 and 2600 nucleotides from the 3' end of rASV RNA, which corresponds to the src region of SR-A RNA mapped previously. Furthermore, viral RNAs of two td mutants isolated from a clone of rASV lack most src-specific oligonucleotides, including the three new ones. No differences were found among RNAs of td, SR-A, and rASV in the regions outside of src. Our results indicate that RNA sequences that rASVs have acquired from cells in the process of conversion from td virus to transforming virus are mapped within the src region and segregate with the transforming function. Some of the sequences are new and some are identical with those in SR-A RNA."}
{"id": "PMID:215999", "title": "Specific RNA sequences and gene products of MC29 avian acute leukemia virus.", "content": "The 28S RNA of the defective avian acute leukemia virus MC29 contains two sets of sequences: 60% are hybridized by DNA complementary to other avian tumor virus RNAs (group-specific cDNA) and 40% are hybridized only by MC29-specific cDNA. Specific and group-specific sequences of viral RNA, defined in terms of their large RNase T(1)-resistant oligonucleotides, were located on a map of all large T(1) oligonucleotides of viral RNA. Oligonucleotides representing MC29-specific sequences of viral RNA mapped between 0.4 and 0.7 unit from the 3'-poly(A) end. Oligonucleotides of group-specific sequences mapped between 0 and 0.4 and between 0.7 and 1 map unit. Cell-free translation of viral RNA yielded three proteins with approximate molecular weights of 120,000, 56,000, and 37,000, termed P120(mc), P56(mc), and P37(mc). P120(mc) contained both MC29-specific peptides and serological determinants and peptides of the conserved, internal group-specific antigens of avian tumor viruses. P120(mc) is translated only from full-length 28S RNA. Furthermore, MC29 RNA contains sequences related to the group-specific antigen gene (gag), near the 5' end, which are followed by MC29-specific sequences. We conclude that this protein is translated from the 5' 60% of the RNA, and that it includes a segment translated from the specific sequences. It is suggested that the transforming (onc) gene of MC29 may consists of the specific and some group-specific RNA sequences and that P120(mc), which is also found in transformed cells, may be the onc gene product.", "contents": "Specific RNA sequences and gene products of MC29 avian acute leukemia virus. The 28S RNA of the defective avian acute leukemia virus MC29 contains two sets of sequences: 60% are hybridized by DNA complementary to other avian tumor virus RNAs (group-specific cDNA) and 40% are hybridized only by MC29-specific cDNA. Specific and group-specific sequences of viral RNA, defined in terms of their large RNase T(1)-resistant oligonucleotides, were located on a map of all large T(1) oligonucleotides of viral RNA. Oligonucleotides representing MC29-specific sequences of viral RNA mapped between 0.4 and 0.7 unit from the 3'-poly(A) end. Oligonucleotides of group-specific sequences mapped between 0 and 0.4 and between 0.7 and 1 map unit. Cell-free translation of viral RNA yielded three proteins with approximate molecular weights of 120,000, 56,000, and 37,000, termed P120(mc), P56(mc), and P37(mc). P120(mc) contained both MC29-specific peptides and serological determinants and peptides of the conserved, internal group-specific antigens of avian tumor viruses. P120(mc) is translated only from full-length 28S RNA. Furthermore, MC29 RNA contains sequences related to the group-specific antigen gene (gag), near the 5' end, which are followed by MC29-specific sequences. We conclude that this protein is translated from the 5' 60% of the RNA, and that it includes a segment translated from the specific sequences. It is suggested that the transforming (onc) gene of MC29 may consists of the specific and some group-specific RNA sequences and that P120(mc), which is also found in transformed cells, may be the onc gene product."}
{"id": "PMID:216000", "title": "Resolution of cytochrome oxidase into two component complexes.", "content": "Cytochrome c oxidase (ferrocytochrome c: oxygen oxidoreductase, EC 1.9.3.1) has been resolved into a pair of complexes of unequal molecular weight. The larger complex (electron transfer complex) contains exclusively the oxidation-reduction proteins characteristic of cytochrome oxidase; the smaller complex (ion transfer complex) shows exclusively the capability for cation-dependent induction of the fluorescence of 8-anilino-1-naphthalenesulfonic acid--a capability demonstrable in preparations of cytochrome oxidase. The duplex nature of cytochrome oxidase has important implications for the mechanism of energy coupling.", "contents": "Resolution of cytochrome oxidase into two component complexes. Cytochrome c oxidase (ferrocytochrome c: oxygen oxidoreductase, EC 1.9.3.1) has been resolved into a pair of complexes of unequal molecular weight. The larger complex (electron transfer complex) contains exclusively the oxidation-reduction proteins characteristic of cytochrome oxidase; the smaller complex (ion transfer complex) shows exclusively the capability for cation-dependent induction of the fluorescence of 8-anilino-1-naphthalenesulfonic acid--a capability demonstrable in preparations of cytochrome oxidase. The duplex nature of cytochrome oxidase has important implications for the mechanism of energy coupling."}
{"id": "PMID:216001", "title": "Translation of polyoma virus T antigens in vitro.", "content": "Polyoma virus-specific RNA isolated from the cytoplasm of lytically infected cells can be translated in vitro to yield three T antigens, of Mrs approximately 90,000, 60,000, and 22,000. The tryptic peptide patterns of the T antigens synthesized in vitro are similar or identical to the patterns of the corresponding proteins in polyoma-infected cells. All three proteins incorporate methionine donated from initiator tRNA in vitro. Polyoma cRNA codes for a protein that is slightly larger than the 22,000 T antigen and that, by other criteria, is similar to the 22,000 T antigen. Translation of cRNA does not yield the 90,000 and 60,000 T antigens, suggesting that the generation of the mRNAs for these T antigens requires the removal of intervening sequences. The mRNA for the 90,000 T antigen is smaller than the mRNAs for the 22,000 and 60,000 proteins. All three proteins share common NH2-terminal sequences, and the 60,000 T antigen may be translated partially in a different reading frame from sequences also coding for the 90,000 T antigen. The demonstration that polyoma virus codes for three different T antigens raises the possibility that all three proteins may be involved in cell transformation.", "contents": "Translation of polyoma virus T antigens in vitro. Polyoma virus-specific RNA isolated from the cytoplasm of lytically infected cells can be translated in vitro to yield three T antigens, of Mrs approximately 90,000, 60,000, and 22,000. The tryptic peptide patterns of the T antigens synthesized in vitro are similar or identical to the patterns of the corresponding proteins in polyoma-infected cells. All three proteins incorporate methionine donated from initiator tRNA in vitro. Polyoma cRNA codes for a protein that is slightly larger than the 22,000 T antigen and that, by other criteria, is similar to the 22,000 T antigen. Translation of cRNA does not yield the 90,000 and 60,000 T antigens, suggesting that the generation of the mRNAs for these T antigens requires the removal of intervening sequences. The mRNA for the 90,000 T antigen is smaller than the mRNAs for the 22,000 and 60,000 proteins. All three proteins share common NH2-terminal sequences, and the 60,000 T antigen may be translated partially in a different reading frame from sequences also coding for the 90,000 T antigen. The demonstration that polyoma virus codes for three different T antigens raises the possibility that all three proteins may be involved in cell transformation."}
{"id": "PMID:216002", "title": "Compartmentalization of cyclic AMP-dependent protein kinases in human erythrocytes.", "content": "The human erythrocyte contains two types of cyclic AMP-dependent protein kinase. The membrane-associated protein kinase holoenzyme can be released intact by hypotonic treatment at alkaline pH. Chromatography on DEAE-cellulose and molecular weight determinations demonstrate that this enzyme is a type I cyclic AMP-dependent protein kinase, while the predominant cyclic AMP-dependent protein kinase found in the cytoplasm is type II. The catalytic subunits of the two types of kinase found in the erythrocyte are identical, but the regulatory subunits, which distinguish the two types of kinase, determine their localization within the cell. It is proposed that the regulatory subunit of the type I enzyme, in addition to binding the catalytic subunit, interacts specifically with one or more membrane proteins and that this interaction may serve to position the kinase in preferential proximity to protein substrates.", "contents": "Compartmentalization of cyclic AMP-dependent protein kinases in human erythrocytes. The human erythrocyte contains two types of cyclic AMP-dependent protein kinase. The membrane-associated protein kinase holoenzyme can be released intact by hypotonic treatment at alkaline pH. Chromatography on DEAE-cellulose and molecular weight determinations demonstrate that this enzyme is a type I cyclic AMP-dependent protein kinase, while the predominant cyclic AMP-dependent protein kinase found in the cytoplasm is type II. The catalytic subunits of the two types of kinase found in the erythrocyte are identical, but the regulatory subunits, which distinguish the two types of kinase, determine their localization within the cell. It is proposed that the regulatory subunit of the type I enzyme, in addition to binding the catalytic subunit, interacts specifically with one or more membrane proteins and that this interaction may serve to position the kinase in preferential proximity to protein substrates."}
{"id": "PMID:216003", "title": "Endogenous viral genes of the White Leghorn chicken: common site of residence and sites associated with specific phenotypes of viral gene expression.", "content": "The DNAs from greater than 150 individual White Leghorn chickens were digested with restriction endonucleases BamHI, EcoRI, HindIII, and Sst I, fractionated by gel electrophoresis, denatured, and transferred to nitrocellulose filters. Fragments containing the endogenous viral genes were detected by hybridization with 70S Rous associated virus type 2[32P]RNA. Embryos of several different phenotypes with respect to production of the endogenous virus and expression of viral group-specific antigen and viral envelope protein were analyzed. DNA from birds of each phenotype produced a distinctive pattern of fragments containing viral genetic information. Individual fragments were seen to segregate as genetic loci in mating experiments. From the fragment patterns and the segregation data, the following conclusions were drawn with respect to the sites of residence in the chicken chromosome of the endogenous viral genes: (i) the DNA of all chickens contains viral genetic information in at least one site, and this site of residence appears to be the same in all chickens analyzed; (ii) four other sites have been identified, and the presence of viral information at each of these sites is always accompanied by a specific phenotype of endogenous viral gene expression; (iii) in addition to the above-mentioned five sites, a small number of other sites have been identified which are not associated with a known phenotype.", "contents": "Endogenous viral genes of the White Leghorn chicken: common site of residence and sites associated with specific phenotypes of viral gene expression. The DNAs from greater than 150 individual White Leghorn chickens were digested with restriction endonucleases BamHI, EcoRI, HindIII, and Sst I, fractionated by gel electrophoresis, denatured, and transferred to nitrocellulose filters. Fragments containing the endogenous viral genes were detected by hybridization with 70S Rous associated virus type 2[32P]RNA. Embryos of several different phenotypes with respect to production of the endogenous virus and expression of viral group-specific antigen and viral envelope protein were analyzed. DNA from birds of each phenotype produced a distinctive pattern of fragments containing viral genetic information. Individual fragments were seen to segregate as genetic loci in mating experiments. From the fragment patterns and the segregation data, the following conclusions were drawn with respect to the sites of residence in the chicken chromosome of the endogenous viral genes: (i) the DNA of all chickens contains viral genetic information in at least one site, and this site of residence appears to be the same in all chickens analyzed; (ii) four other sites have been identified, and the presence of viral information at each of these sites is always accompanied by a specific phenotype of endogenous viral gene expression; (iii) in addition to the above-mentioned five sites, a small number of other sites have been identified which are not associated with a known phenotype."}
{"id": "PMID:216004", "title": "Origin of DNA replication in papovavirus chromatin is recognized by endogenous endonuclease.", "content": "Isolated simian virus 40 (SV40) and polyoma nucleoprotein complexes contain endonuclease that, under in vitro conditions, converts part (up to 30%) of the covalently closed superhelical DNA to full-length linear rods. The positions of the cleavage sites within the genomes of SV40 and polyoma were determined by digestion with various single-cut restriction endonucleases and subsequent agarose gel electrophoresis of the cleavage products. Both SV40 and polyoma covalently closed superhelical DNA were cleaved open at their respective origins of DNA replication (+/- 75 base pairs). The full-length linear DNA rods whose ends map adjacent to the origin of DNA replication could also be isolated by sodium dodecyl sulfate/phenol extraction both from SV40-infected permissive cells and from purified SV40 virions. These data reveal the presence of a unique structure of the papovavirus chromatin close to the initiation site of DNA replication.", "contents": "Origin of DNA replication in papovavirus chromatin is recognized by endogenous endonuclease. Isolated simian virus 40 (SV40) and polyoma nucleoprotein complexes contain endonuclease that, under in vitro conditions, converts part (up to 30%) of the covalently closed superhelical DNA to full-length linear rods. The positions of the cleavage sites within the genomes of SV40 and polyoma were determined by digestion with various single-cut restriction endonucleases and subsequent agarose gel electrophoresis of the cleavage products. Both SV40 and polyoma covalently closed superhelical DNA were cleaved open at their respective origins of DNA replication (+/- 75 base pairs). The full-length linear DNA rods whose ends map adjacent to the origin of DNA replication could also be isolated by sodium dodecyl sulfate/phenol extraction both from SV40-infected permissive cells and from purified SV40 virions. These data reveal the presence of a unique structure of the papovavirus chromatin close to the initiation site of DNA replication."}
{"id": "PMID:216005", "title": "Refolding of a bifunctional enzyme and its monofunctional fragment.", "content": "The renaturation of the bifunctional enzyme aspartokinase II-homoserine dehydrogenase II has been studied by using the reappearance of its two activities. The same kinetics of renaturation are obtained for the dehydrogenase (EC 1.1.1.3) and the kinase activity (EC 2.7.2.4). The mechanism of refolding of the enzyme apparently involves two steps, a folding step occurring within a monomer and a subsequent dimerization step. The reappearance of the two activities depends on this dimerization step, suggesting that monomeric species are inactive. A proteolytic fragment possessing full dehydrogenase activity is shown to be able to renature, as judged by the recovery of its activity. In this case also, the refolding depends on the formation of dimeric species. However, the refolding of this fragment is much faster than that of the dehydrogenase region in the intact enzyme. These results suggest that, although the dehydrogenase region can refold by itself when isolated as a fragment, refolding of this same region in the whole protein involves interactions with the remainder of the protein.", "contents": "Refolding of a bifunctional enzyme and its monofunctional fragment. The renaturation of the bifunctional enzyme aspartokinase II-homoserine dehydrogenase II has been studied by using the reappearance of its two activities. The same kinetics of renaturation are obtained for the dehydrogenase (EC 1.1.1.3) and the kinase activity (EC 2.7.2.4). The mechanism of refolding of the enzyme apparently involves two steps, a folding step occurring within a monomer and a subsequent dimerization step. The reappearance of the two activities depends on this dimerization step, suggesting that monomeric species are inactive. A proteolytic fragment possessing full dehydrogenase activity is shown to be able to renature, as judged by the recovery of its activity. In this case also, the refolding depends on the formation of dimeric species. However, the refolding of this fragment is much faster than that of the dehydrogenase region in the intact enzyme. These results suggest that, although the dehydrogenase region can refold by itself when isolated as a fragment, refolding of this same region in the whole protein involves interactions with the remainder of the protein."}
{"id": "PMID:216006", "title": "Escherichia coli mutants defective in dipeptidyl carboxypeptidase.", "content": "Two independent mutants of Escherichia coli deficient in dipeptidyl carboxypeptidase activity (Dep-) were isolated after mutagenesis with ethyl methanesulfonate. Mating experiments and introduction of specific episomes indicated that the responsible gene was located at approximately 27--31 min on the E. coli chromosome. The Dep- mutants differed from the parental strain in their inability to grow with N-acetylalanylalanylalanine as the sole nitrogen source. Revertants selected for growth on this substrate of the enzyme were found to have reacquired the activity. Enzyme activity was highly sensitive to inhibition by 1-(D-3-mercapto-2-methylpropanoyl)-L-proline (SQ 14225), a potent inhibitor of mammalian dipeptidyl carboxypeptidase (angiotensin-converting enzyme, peptidyl dipeptidase, EC 3.4.15.1). This compound also reduced the rate of growth of the wild type with N-acetylalanylalanylalanine but not with ammonium sulfate. A fraction of the enzyme was released into the medium by osmotic shock, indicating that its presence in the periplasmic space may account for growth with N-acetylated peptides that cannot be taken up by E. coli. In addition to providing information about the specific role of this exopeptidase in E. coli, the Dep- mutants may prove useful for delineating the regulation and cellular function of dipeptidyl carboxypeptidases in higher organisms.", "contents": "Escherichia coli mutants defective in dipeptidyl carboxypeptidase. Two independent mutants of Escherichia coli deficient in dipeptidyl carboxypeptidase activity (Dep-) were isolated after mutagenesis with ethyl methanesulfonate. Mating experiments and introduction of specific episomes indicated that the responsible gene was located at approximately 27--31 min on the E. coli chromosome. The Dep- mutants differed from the parental strain in their inability to grow with N-acetylalanylalanylalanine as the sole nitrogen source. Revertants selected for growth on this substrate of the enzyme were found to have reacquired the activity. Enzyme activity was highly sensitive to inhibition by 1-(D-3-mercapto-2-methylpropanoyl)-L-proline (SQ 14225), a potent inhibitor of mammalian dipeptidyl carboxypeptidase (angiotensin-converting enzyme, peptidyl dipeptidase, EC 3.4.15.1). This compound also reduced the rate of growth of the wild type with N-acetylalanylalanylalanine but not with ammonium sulfate. A fraction of the enzyme was released into the medium by osmotic shock, indicating that its presence in the periplasmic space may account for growth with N-acetylated peptides that cannot be taken up by E. coli. In addition to providing information about the specific role of this exopeptidase in E. coli, the Dep- mutants may prove useful for delineating the regulation and cellular function of dipeptidyl carboxypeptidases in higher organisms."}
{"id": "PMID:216007", "title": "Construction of bacterial plasmids that contain the nucleotide sequence for bovine corticotropin-beta-lipotropin precursor.", "content": "mRNA that encodes the common peptide precursor for the hormones corticotropin and beta-lipotropin was purified from the neurointermediate lobe of bovine pituitaries, and double-stranded cDNA species synthesized from this template were cloned in Escherichia coli X1776 by inserting them into the Pst I endonuclease cleavage site of the pBR322 plasmid using poly(dG)poly(dC) homopolymeric extensions. Certain of the cloned cDNA inserts contain nucleotides corresponding to the complete amino acid sequence of bovine corticotropin and a coding sequence that corresponds to at least the first portion of bovine beta-lipotropin. The nucleotide sequences coding for corticotropin and beta-lipotropin are separated on the cDNA by a 6-base-pair sequence encoding lysine and arginine, indicating that the carboxyl terminus of corticotropin is connected on the precursor peptide with the amino terminus of beta-lipotropin by these two amino acids. In addition, the cloned cDNA insert is characterized by an unusually high C+G nucleotide base content as well as by a number of DNA sequence duplications.", "contents": "Construction of bacterial plasmids that contain the nucleotide sequence for bovine corticotropin-beta-lipotropin precursor. mRNA that encodes the common peptide precursor for the hormones corticotropin and beta-lipotropin was purified from the neurointermediate lobe of bovine pituitaries, and double-stranded cDNA species synthesized from this template were cloned in Escherichia coli X1776 by inserting them into the Pst I endonuclease cleavage site of the pBR322 plasmid using poly(dG)poly(dC) homopolymeric extensions. Certain of the cloned cDNA inserts contain nucleotides corresponding to the complete amino acid sequence of bovine corticotropin and a coding sequence that corresponds to at least the first portion of bovine beta-lipotropin. The nucleotide sequences coding for corticotropin and beta-lipotropin are separated on the cDNA by a 6-base-pair sequence encoding lysine and arginine, indicating that the carboxyl terminus of corticotropin is connected on the precursor peptide with the amino terminus of beta-lipotropin by these two amino acids. In addition, the cloned cDNA insert is characterized by an unusually high C+G nucleotide base content as well as by a number of DNA sequence duplications."}
{"id": "PMID:216008", "title": "Demonstration of an ecdysteroid receptor in a cultured cell line of Drosophila melanogaster.", "content": "Incubation of the high-speed supernatant from the Kc cell line of Drosophila melanogaster with [3H]ponasterone A results in significant binding of the ligand as determined by gel filtration and dextran-coated charcoal binding assays. In vivo exposure of the Kc line to [3H]ponasterone A for 30 min results in a marked binding of the ligand by a KCl-soluble nuclear extract. With both the cytosol and nuclear preparations the binding has specificity and a low dissociation constant (3 X 10(-9) M). In addition the labeling of the nuclear preparation exhibits a saturation at approximately 7 X 10(-10) M which probably reflects the molar concentration of cytoplasmic receptors.", "contents": "Demonstration of an ecdysteroid receptor in a cultured cell line of Drosophila melanogaster. Incubation of the high-speed supernatant from the Kc cell line of Drosophila melanogaster with [3H]ponasterone A results in significant binding of the ligand as determined by gel filtration and dextran-coated charcoal binding assays. In vivo exposure of the Kc line to [3H]ponasterone A for 30 min results in a marked binding of the ligand by a KCl-soluble nuclear extract. With both the cytosol and nuclear preparations the binding has specificity and a low dissociation constant (3 X 10(-9) M). In addition the labeling of the nuclear preparation exhibits a saturation at approximately 7 X 10(-10) M which probably reflects the molar concentration of cytoplasmic receptors."}
{"id": "PMID:216009", "title": "Ecdysteroid receptors in imaginal discs of Drosophila melanogaster.", "content": "[3H]Ponasterone A (PNA) of high specific activity has been used to identify and begin characterization of ecdysteroid (formerly called ecdysone) receptors in cytoplasmic and nuclear fractions of imaginal discs of Drosophila melanogaster. The equilibrium Kd of the observed macromolecular binding, 3--4 X 10(-9) M PNA, is in good agreement with the minimal concentration required for induction of complete morphogenesis in vitro, 4.2 X 10(-9) M PNA. Binding is analog specific and has kinetics consistent with a role in hormone response. On gentle homogenization, less than 5% of the binding capacity of the cell is released as soluble receptor; the other 95% remains with the nuclear fraction. This nuclear fraction specifically binds [3H]PNA in vitro. Greater than 95% of nuclear PNA receptors are released by extraction with 0.3 M KCl. The binding properties of the nuclear receptors are indistinguishable from those of the cytosol fraction or of the whole cell.", "contents": "Ecdysteroid receptors in imaginal discs of Drosophila melanogaster. [3H]Ponasterone A (PNA) of high specific activity has been used to identify and begin characterization of ecdysteroid (formerly called ecdysone) receptors in cytoplasmic and nuclear fractions of imaginal discs of Drosophila melanogaster. The equilibrium Kd of the observed macromolecular binding, 3--4 X 10(-9) M PNA, is in good agreement with the minimal concentration required for induction of complete morphogenesis in vitro, 4.2 X 10(-9) M PNA. Binding is analog specific and has kinetics consistent with a role in hormone response. On gentle homogenization, less than 5% of the binding capacity of the cell is released as soluble receptor; the other 95% remains with the nuclear fraction. This nuclear fraction specifically binds [3H]PNA in vitro. Greater than 95% of nuclear PNA receptors are released by extraction with 0.3 M KCl. The binding properties of the nuclear receptors are indistinguishable from those of the cytosol fraction or of the whole cell."}
{"id": "PMID:216010", "title": "Monovalent antibodies directed to transformation-sensitive membrane components inhibit the process of viral transformation.", "content": "Monovalent antibodies (Fab) directed to two classes of transformation-sensitive cell surface components, ganglioside and galactoprotein a (Gap a), inhibit the process of oncogenic viral transformation of cells. Mouse 3T3 cells infected with murine sarcoma virus were not transformed in terms of morphology change and enhancement of sugar uptake when the infected cells were cultured in the presence of monovalent antibodies directed to GM(1) ganglioside or to Gap a. Transformation inhibitory activity of these cell surface ligands was not related to cell growth inhibition because the monovalent antibodies to globoside and divalent Con A were growth inhibitory but did not inhibit oncogenic transformation. Neither anti-GM(1) Fab nor anti-Gap a Fab inhibited virus production. The transformation inhibitory activity of antiganglioside and anti-Gap a Fab was additionally assessed by inhibiting the transformed phenotype in NRK cell lines with mutants of avian sarcoma virus that are temperature sensitive for expression of the transformation phenotype (NRK/LA25). In this cell line, the GM(3) ganglioside (not GM(1)) and Gap a were transformation-sensitive cell surface components. The expression at permissive temperature of transformed phenotypes, such as morphology change and capability of growth in 0.3% agar, was inhibited by preincubation of the cells with anti-GM(3) Fab or anti-Gap a Fab.GM(3) labeling of NRK/LA25 cells decreased at permissive temperature, whereas preincubation of cells with anti-Gap a, which induces the inhibition of transformation after a temperature shift, prevented the decline of GM(3) label on the cell surface. The data suggest a possible correlation between GM(3) and Gap a expression. Application of monovalent antibodies to these transformation-sensitive components may prevent changes of these components on cell surfaces, and thus may result in abortion of phenotypic expression of transformation, although the transforming gene (src) has been set active. These results indicate that pericellular structures influence gene expression.", "contents": "Monovalent antibodies directed to transformation-sensitive membrane components inhibit the process of viral transformation. Monovalent antibodies (Fab) directed to two classes of transformation-sensitive cell surface components, ganglioside and galactoprotein a (Gap a), inhibit the process of oncogenic viral transformation of cells. Mouse 3T3 cells infected with murine sarcoma virus were not transformed in terms of morphology change and enhancement of sugar uptake when the infected cells were cultured in the presence of monovalent antibodies directed to GM(1) ganglioside or to Gap a. Transformation inhibitory activity of these cell surface ligands was not related to cell growth inhibition because the monovalent antibodies to globoside and divalent Con A were growth inhibitory but did not inhibit oncogenic transformation. Neither anti-GM(1) Fab nor anti-Gap a Fab inhibited virus production. The transformation inhibitory activity of antiganglioside and anti-Gap a Fab was additionally assessed by inhibiting the transformed phenotype in NRK cell lines with mutants of avian sarcoma virus that are temperature sensitive for expression of the transformation phenotype (NRK/LA25). In this cell line, the GM(3) ganglioside (not GM(1)) and Gap a were transformation-sensitive cell surface components. The expression at permissive temperature of transformed phenotypes, such as morphology change and capability of growth in 0.3% agar, was inhibited by preincubation of the cells with anti-GM(3) Fab or anti-Gap a Fab.GM(3) labeling of NRK/LA25 cells decreased at permissive temperature, whereas preincubation of cells with anti-Gap a, which induces the inhibition of transformation after a temperature shift, prevented the decline of GM(3) label on the cell surface. The data suggest a possible correlation between GM(3) and Gap a expression. Application of monovalent antibodies to these transformation-sensitive components may prevent changes of these components on cell surfaces, and thus may result in abortion of phenotypic expression of transformation, although the transforming gene (src) has been set active. These results indicate that pericellular structures influence gene expression."}
{"id": "PMID:216011", "title": "Establishment of preadipocyte clonal line from epididymal fat pad of ob/ob mouse that responds to insulin and to lipolytic hormones.", "content": "A clonal cell line that responds to insulin and to lipolytic hormones has been established from the epididymal fat pad of the C57BL/6J ob/ob mouse. This line, designated ob 17, has a doubling time of 12.5 or 19 hr in 10% or 1% fetal calf serum, respectively. It presents a heterogeneous chromosome number with 40% of the cells containing 35-44 chromosomes and expresses the characteristic H2-LA antigen. After cessation of growth, ob 17 cells accumulate droplets of triglycerides; this accumulation occurs to a significant extent even in the absence of insulin normally added after confluence. Lipoprotein lipase activity is negligible in exponentially growing cells but appears at its maximal level just after confluence with or without insulin. Acid:CoA ligase and acylCoA:diglyceride acyltransferase develop later than lipoprotein lipase. The appearance of lipolytic and lipogenic enzymes, but not of triglycerides, seems to be independent of the presence of lipoproteins or of unesterified fatty acids in the culture medium. Therefore, the differentiation program becomes operative when growth is arrested, and differentiation occurs, providing a source of exogenous lipids. Differentiated ob 17 cells in which endogenous triglycerides have been prelabeled on the fatty acid moiety do respond to epinephrine and corticotropin by release of radioactive fatty acid. This lipolytic response is counteracted by prior addition of insulin. The ob 17 cell line appears to be a useful model for study of growth and differentiation of adipose cells as compared to preadipocyte cell lines from the nongenetically obese mouse.", "contents": "Establishment of preadipocyte clonal line from epididymal fat pad of ob/ob mouse that responds to insulin and to lipolytic hormones. A clonal cell line that responds to insulin and to lipolytic hormones has been established from the epididymal fat pad of the C57BL/6J ob/ob mouse. This line, designated ob 17, has a doubling time of 12.5 or 19 hr in 10% or 1% fetal calf serum, respectively. It presents a heterogeneous chromosome number with 40% of the cells containing 35-44 chromosomes and expresses the characteristic H2-LA antigen. After cessation of growth, ob 17 cells accumulate droplets of triglycerides; this accumulation occurs to a significant extent even in the absence of insulin normally added after confluence. Lipoprotein lipase activity is negligible in exponentially growing cells but appears at its maximal level just after confluence with or without insulin. Acid:CoA ligase and acylCoA:diglyceride acyltransferase develop later than lipoprotein lipase. The appearance of lipolytic and lipogenic enzymes, but not of triglycerides, seems to be independent of the presence of lipoproteins or of unesterified fatty acids in the culture medium. Therefore, the differentiation program becomes operative when growth is arrested, and differentiation occurs, providing a source of exogenous lipids. Differentiated ob 17 cells in which endogenous triglycerides have been prelabeled on the fatty acid moiety do respond to epinephrine and corticotropin by release of radioactive fatty acid. This lipolytic response is counteracted by prior addition of insulin. The ob 17 cell line appears to be a useful model for study of growth and differentiation of adipose cells as compared to preadipocyte cell lines from the nongenetically obese mouse."}
{"id": "PMID:216012", "title": "DNAs of simian virus 40 and polyoma direct the synthesis of viral tumor antigens and capsid proteins in Xenopus oocytes.", "content": "Purified simian virus 40 and polyoma DNAs injected into nuclei of Xenopus oocytes were transcribed and subsequently translated into virus-specific tumor antigens and capsid proteins. Simian virus 40 large and small tumor antigens synthesized in the oocytes were indistinguishable, by gel electrophoresis and [35S]methionine-labeled tryptic peptide mapping, from the corresponding polypeptides synthesized in CV-1 African green monkey cells. The synthesis of large simian virus 40 tumor antigen implies the correct splicing of its mRNA, which is complementary to nonadjacent nucleotide sequences in the early region of the viral genome. Polyoma DNA directed synthesis of two polyoma tumor antigen polypeptides, 57,000 Mr and small tumor antigen, and of the main capsid protein.", "contents": "DNAs of simian virus 40 and polyoma direct the synthesis of viral tumor antigens and capsid proteins in Xenopus oocytes. Purified simian virus 40 and polyoma DNAs injected into nuclei of Xenopus oocytes were transcribed and subsequently translated into virus-specific tumor antigens and capsid proteins. Simian virus 40 large and small tumor antigens synthesized in the oocytes were indistinguishable, by gel electrophoresis and [35S]methionine-labeled tryptic peptide mapping, from the corresponding polypeptides synthesized in CV-1 African green monkey cells. The synthesis of large simian virus 40 tumor antigen implies the correct splicing of its mRNA, which is complementary to nonadjacent nucleotide sequences in the early region of the viral genome. Polyoma DNA directed synthesis of two polyoma tumor antigen polypeptides, 57,000 Mr and small tumor antigen, and of the main capsid protein."}
{"id": "PMID:216013", "title": "Infection with paramyxoviruses stimulates synthesis of cellular polypeptides that are also stimulated in cells transformed by Rous sarcoma virus or deprived of glucose.", "content": "Infection of several types of cultured cells with the paramyxoviruses simian virus 5 and Sendai virus stimulates synthesis of four polypeptides (I-IV) with molecular weights of approximately 99,000, 97,000, 86,000, and 78,000, respectively. That these are host polypeptides encoded in cellular mRNAs has been shown by the inhibition of their synthesis by actinomycin D and by the similarity of the peptide maps of them and of polypeptides with the same electrophoretic mobility from uninfected cells. Peptide mapping as well as identical migration in polyacrylamide gels has also indicated that polypeptides I, II, and IV are the same as plasma membrane polypeptides whose synthesis is enhanced in cells transformed by Rous sarcoma virus and in normal cells by glucose deprivation or treatment with 2-deoxyglucose. Polypeptides I and II appear to be the same polypeptides, with the observed differences in migration reflecting the glycosylation of polypeptide I, a relationship previously shown to exist between polypeptides in glucose-deprived and glucose-fed cells. Infection with paramyxoviruses does not significantly increase the transport of glucose by cells, and the maintenance of a high concentration of glucose in the medium does not prevent the enhanced synthesis of these polypeptides. This is in contrast to the situation in transformed cells in which stimulation of synthesis of these polypeptides is secondary to depletion of glucose in the medium due to increased glucose uptake by the cells. Thus, although paramyxovirus infection and transformation by Rous sarcoma virus result in stimulation of the synthesis of the same membrane polypeptides, the mechanism of stimulation differs.", "contents": "Infection with paramyxoviruses stimulates synthesis of cellular polypeptides that are also stimulated in cells transformed by Rous sarcoma virus or deprived of glucose. Infection of several types of cultured cells with the paramyxoviruses simian virus 5 and Sendai virus stimulates synthesis of four polypeptides (I-IV) with molecular weights of approximately 99,000, 97,000, 86,000, and 78,000, respectively. That these are host polypeptides encoded in cellular mRNAs has been shown by the inhibition of their synthesis by actinomycin D and by the similarity of the peptide maps of them and of polypeptides with the same electrophoretic mobility from uninfected cells. Peptide mapping as well as identical migration in polyacrylamide gels has also indicated that polypeptides I, II, and IV are the same as plasma membrane polypeptides whose synthesis is enhanced in cells transformed by Rous sarcoma virus and in normal cells by glucose deprivation or treatment with 2-deoxyglucose. Polypeptides I and II appear to be the same polypeptides, with the observed differences in migration reflecting the glycosylation of polypeptide I, a relationship previously shown to exist between polypeptides in glucose-deprived and glucose-fed cells. Infection with paramyxoviruses does not significantly increase the transport of glucose by cells, and the maintenance of a high concentration of glucose in the medium does not prevent the enhanced synthesis of these polypeptides. This is in contrast to the situation in transformed cells in which stimulation of synthesis of these polypeptides is secondary to depletion of glucose in the medium due to increased glucose uptake by the cells. Thus, although paramyxovirus infection and transformation by Rous sarcoma virus result in stimulation of the synthesis of the same membrane polypeptides, the mechanism of stimulation differs."}
{"id": "PMID:216014", "title": "Detection of viral sequences of low reiteration frequency by in situ hybridization.", "content": "The sensitivity of in situ hybridization has been increased at least 10-fold by hybridizing in cDNA excess, by increasing the diffusion of the cDNA through the cells, by hybridizing at optimum temperature, and by stabilizing hybrids during autoradiography. Saturation of intracellular RNA with [3H]cDNA has been achieved. The assay is quantitative. In situ hybridization has been used to detect and quantitate visna virus RNA in infected cells. By using [3H]cDNA with specific activity of 2 X 10(8) dpm/micrograms and conditions that reduce background to negligible levels, 10--20 copies of viral RNA per cell can be detected and quantitated after 2 days of autoradiographic exposure.", "contents": "Detection of viral sequences of low reiteration frequency by in situ hybridization. The sensitivity of in situ hybridization has been increased at least 10-fold by hybridizing in cDNA excess, by increasing the diffusion of the cDNA through the cells, by hybridizing at optimum temperature, and by stabilizing hybrids during autoradiography. Saturation of intracellular RNA with [3H]cDNA has been achieved. The assay is quantitative. In situ hybridization has been used to detect and quantitate visna virus RNA in infected cells. By using [3H]cDNA with specific activity of 2 X 10(8) dpm/micrograms and conditions that reduce background to negligible levels, 10--20 copies of viral RNA per cell can be detected and quantitated after 2 days of autoradiographic exposure."}
{"id": "PMID:216015", "title": "Interaction of bombesin and litorin with specific membrane receptors on pancreatic acinar cells.", "content": "We have prepared (125)I-labeled [Tyr(4)]bombesin and have examined the kinetics, stoichiometry, and chemical specificity with which the labeled peptide binds to dispersed acini from guinea pig pancreas. Binding of (125)I-labeled [Tyr(4)]-bombesin was saturable, temperature-dependent, and reversible and reflected interaction of the labeled peptide with a single class of binding sites on the plasma membrane of pancreatic acinar cells. Each acinar cell possessed approximately 5000 binding sites, and binding of the tracer to these sites could be inhibited by [Tyr(4)]bombesin [concentration for half-maximal effect (Kd), 2 nM], bombesin (Kd, 4 nM), or litorin (Kd, 40 nM) but not by eledoisin, physalemin, somatostatin, carbachol, atropine, secretin, vasocative intestinal peptide, neurotensin, or bovine pancreatic polypeptide. At high concentrations (>0.1 muM), cholecystokinin and caerulein each caused a small (15-20%) reduction in binding of lableled [Tyr(4)]bombesin. With bombesin, litorin, and [Tyr(4)]bombesin, there was a close correlation between the relative potency for inhibition of binding of labeled [Tyr(4)]bombesin and that for stimulation of amylase secretion. For a given peptide, however, a 10-fold higher concentration was required for half-maximal inhibition of binding than for half-maximal stimulation of amylase secretion, calcium outflux, or cyclic GMP accumulation. These results indicate that dispersed acini from guinea pig pancreas possess a single class of receptors that interact with [Tyr(4)]bombesin, bombesin, and litorin and that occupation of 25% of these receptors will cause a maximal biological response.", "contents": "Interaction of bombesin and litorin with specific membrane receptors on pancreatic acinar cells. We have prepared (125)I-labeled [Tyr(4)]bombesin and have examined the kinetics, stoichiometry, and chemical specificity with which the labeled peptide binds to dispersed acini from guinea pig pancreas. Binding of (125)I-labeled [Tyr(4)]-bombesin was saturable, temperature-dependent, and reversible and reflected interaction of the labeled peptide with a single class of binding sites on the plasma membrane of pancreatic acinar cells. Each acinar cell possessed approximately 5000 binding sites, and binding of the tracer to these sites could be inhibited by [Tyr(4)]bombesin [concentration for half-maximal effect (Kd), 2 nM], bombesin (Kd, 4 nM), or litorin (Kd, 40 nM) but not by eledoisin, physalemin, somatostatin, carbachol, atropine, secretin, vasocative intestinal peptide, neurotensin, or bovine pancreatic polypeptide. At high concentrations (>0.1 muM), cholecystokinin and caerulein each caused a small (15-20%) reduction in binding of lableled [Tyr(4)]bombesin. With bombesin, litorin, and [Tyr(4)]bombesin, there was a close correlation between the relative potency for inhibition of binding of labeled [Tyr(4)]bombesin and that for stimulation of amylase secretion. For a given peptide, however, a 10-fold higher concentration was required for half-maximal inhibition of binding than for half-maximal stimulation of amylase secretion, calcium outflux, or cyclic GMP accumulation. These results indicate that dispersed acini from guinea pig pancreas possess a single class of receptors that interact with [Tyr(4)]bombesin, bombesin, and litorin and that occupation of 25% of these receptors will cause a maximal biological response."}
{"id": "PMID:216016", "title": "Time-dependent resistance or susceptibility of tumor cells to cytotoxic antibody after exposure to a chemotherapeutic agent.", "content": "We report that a chemotherapeutic agent (melphalan) can affect the sensitivity of tumor cells to cytotoxic antibody. Depending on the time interval between drug treatment and subsequent exposure to antibody and complement, the tumor cells can be either more resistant or more susceptible to antibody when compared to control cells. The number of tumor cells surviving the combined treatment was determined by a colony inhibition assay. The two antisera used in this study were directed against either virus-specific or myeloma protein-specific antigens on the surface of S107 murine myeloma cells; identical results were obtained with both sera. Twenty-four hours after exposure to the drug, the number of tumor cells surviving the antibody treatment increased. During this period of increased resistance, the tumor cells were temporarily arrested in the G(2) phase of the cell cycle. After this period of maximal resistance, the effect of cytotoxic antibody on the cells changed such that 4 days after melphalan treatment the cells were significantly more susceptible to the antibody than were the sham-treated control cells. The period of increased susceptibility correlated with an increased density of S107 myeloma protein and viral antigens on the surface of the tumor cells. Eight days after the drug treatment, the susceptibility of the tumor cells and the density of surface antigens both returned to normal levels. This study shows that the correct time interval between exposure to a drug and subsequent treatment with antibody is critical for maximal killing of the tumor cells. The basis for the differential sensitivity of the tumor cells to anti-body may be related to the drug-induced changes in the cell cycle and in antigen expression on the cell surface.", "contents": "Time-dependent resistance or susceptibility of tumor cells to cytotoxic antibody after exposure to a chemotherapeutic agent. We report that a chemotherapeutic agent (melphalan) can affect the sensitivity of tumor cells to cytotoxic antibody. Depending on the time interval between drug treatment and subsequent exposure to antibody and complement, the tumor cells can be either more resistant or more susceptible to antibody when compared to control cells. The number of tumor cells surviving the combined treatment was determined by a colony inhibition assay. The two antisera used in this study were directed against either virus-specific or myeloma protein-specific antigens on the surface of S107 murine myeloma cells; identical results were obtained with both sera. Twenty-four hours after exposure to the drug, the number of tumor cells surviving the antibody treatment increased. During this period of increased resistance, the tumor cells were temporarily arrested in the G(2) phase of the cell cycle. After this period of maximal resistance, the effect of cytotoxic antibody on the cells changed such that 4 days after melphalan treatment the cells were significantly more susceptible to the antibody than were the sham-treated control cells. The period of increased susceptibility correlated with an increased density of S107 myeloma protein and viral antigens on the surface of the tumor cells. Eight days after the drug treatment, the susceptibility of the tumor cells and the density of surface antigens both returned to normal levels. This study shows that the correct time interval between exposure to a drug and subsequent treatment with antibody is critical for maximal killing of the tumor cells. The basis for the differential sensitivity of the tumor cells to anti-body may be related to the drug-induced changes in the cell cycle and in antigen expression on the cell surface."}
{"id": "PMID:216017", "title": "Inhibition of lymphocyte-mediated cytolysis by 3-deazaadenosine: evidence for a methylation reaction essential to cytolysis.", "content": "3-Deazaadenosine (deazaAdo) inhibits lymphocyte-mediated cytolysis in vitro at micromolar concentrations and is potentiated markedly in this activity by L-homocysteine thiolactone. DeazaAdo alone causes a rapid, dose-dependent buildup of S-[(3)H]adenosylhomocysteine (AdoHcy) and S-[(3)H]adenosylmethionine in cytolytic lymphocytes labeled with L-[2-(3)H]methionine; smaller amounts of S-3-[(3)H]deazaadenosylhomocysteine (deazaAdoHcy) are also formed in these cells. The simultaneous addition of deazaAdo and L-homocysteine thiolactone to the lymphocytes results in a massive intracellular accumulation of deazaAdoHcy. Both the inhibition of lymphocyte-mediated cytolysis and the cellular accumulation of [(3)H]AdoHcy caused by deazaAdo alone are reversed rapidly by removal of drug from the medium. However, the inhibition of cytolysis and the large cellular buildup of deazaAdoHcy resulting from treatment of the lymphocytes with deazaAdo plus L-homocysteine thiolactone are dissipated more slowly under these same conditions. Unlike adenosine, deazaAdo is not potentiated in its inhibition of lymphocyte-mediated cytolysis by Ro 20-1724 [4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone], an inhibitor of cyclic AMP phosphodiesterase, and has little or no effect upon the level of lymphocytic cyclic AMP. DeazaAdo is not metabolized detectably to 5'-nucleotides in the lymphocytes and does not cause a decrease in the pool sizes of CTP, UTP, ATP, or GTP. Both AdoHcy and deazaAdoHcy have been reported to be powerful inhibitors of a variety of S-adenosylmethionine-utilizing methyltransferases. The present results, therefore, indicate that the effect of deazaAdo upon lymphocyte-mediated cytolysis is due ultimately to the inhibition of an unidentified but crucial methyltransferase within the cytolytic lymphocytes and provide an insight into the biochemical processes involved in lymphocyte-mediated cytolysis.", "contents": "Inhibition of lymphocyte-mediated cytolysis by 3-deazaadenosine: evidence for a methylation reaction essential to cytolysis. 3-Deazaadenosine (deazaAdo) inhibits lymphocyte-mediated cytolysis in vitro at micromolar concentrations and is potentiated markedly in this activity by L-homocysteine thiolactone. DeazaAdo alone causes a rapid, dose-dependent buildup of S-[(3)H]adenosylhomocysteine (AdoHcy) and S-[(3)H]adenosylmethionine in cytolytic lymphocytes labeled with L-[2-(3)H]methionine; smaller amounts of S-3-[(3)H]deazaadenosylhomocysteine (deazaAdoHcy) are also formed in these cells. The simultaneous addition of deazaAdo and L-homocysteine thiolactone to the lymphocytes results in a massive intracellular accumulation of deazaAdoHcy. Both the inhibition of lymphocyte-mediated cytolysis and the cellular accumulation of [(3)H]AdoHcy caused by deazaAdo alone are reversed rapidly by removal of drug from the medium. However, the inhibition of cytolysis and the large cellular buildup of deazaAdoHcy resulting from treatment of the lymphocytes with deazaAdo plus L-homocysteine thiolactone are dissipated more slowly under these same conditions. Unlike adenosine, deazaAdo is not potentiated in its inhibition of lymphocyte-mediated cytolysis by Ro 20-1724 [4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone], an inhibitor of cyclic AMP phosphodiesterase, and has little or no effect upon the level of lymphocytic cyclic AMP. DeazaAdo is not metabolized detectably to 5'-nucleotides in the lymphocytes and does not cause a decrease in the pool sizes of CTP, UTP, ATP, or GTP. Both AdoHcy and deazaAdoHcy have been reported to be powerful inhibitors of a variety of S-adenosylmethionine-utilizing methyltransferases. The present results, therefore, indicate that the effect of deazaAdo upon lymphocyte-mediated cytolysis is due ultimately to the inhibition of an unidentified but crucial methyltransferase within the cytolytic lymphocytes and provide an insight into the biochemical processes involved in lymphocyte-mediated cytolysis."}
{"id": "PMID:216018", "title": "gamma-Aminobutyric acid receptors visualized in spinal cord cultures by [3H]muscimol autoradiography.", "content": "gamma-Aminobutyric acid (GABA) receptors were visualized in mouse spinal cord explant cultures by [3H]muscimol autoradiography over certain small neurons of the dorsal horn grey matter, in the interneuronal neuropil of dorsal and ventral horns, and (rarely) in small clusters on processes of anterior horn cells. Specificity was indicated in control experiments by inhibition of binding by [3H]muscimol after pretreatment with GABA or a GABA analogue, 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP, isoxazole 16), or with receptor antagonists bicuculline and picrotoxin. Unlabeled muscimol exchanged effectively with [3H]muscimol and produced autoradiographic label in locations indistinguishable from those found in experiments with [3H]muscimol alone. Pretreatment with the GABA uptake and transport inhibitors (-)-nipecotic acid and guvacine did not affect binding with [3H]muscimol. These experiments indicate that explant culture systems can be used for demonstration of functional receptors.", "contents": "gamma-Aminobutyric acid receptors visualized in spinal cord cultures by [3H]muscimol autoradiography. gamma-Aminobutyric acid (GABA) receptors were visualized in mouse spinal cord explant cultures by [3H]muscimol autoradiography over certain small neurons of the dorsal horn grey matter, in the interneuronal neuropil of dorsal and ventral horns, and (rarely) in small clusters on processes of anterior horn cells. Specificity was indicated in control experiments by inhibition of binding by [3H]muscimol after pretreatment with GABA or a GABA analogue, 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP, isoxazole 16), or with receptor antagonists bicuculline and picrotoxin. Unlabeled muscimol exchanged effectively with [3H]muscimol and produced autoradiographic label in locations indistinguishable from those found in experiments with [3H]muscimol alone. Pretreatment with the GABA uptake and transport inhibitors (-)-nipecotic acid and guvacine did not affect binding with [3H]muscimol. These experiments indicate that explant culture systems can be used for demonstration of functional receptors."}
{"id": "PMID:216019", "title": "Biochemical evidence for presynaptic and postsynaptic alpha-adrenoceptors in rat heart membranes: positive homotropic cooperativity of presynaptic binding.", "content": "In crude rat cardiac membrane preparations, [3H]dihydroergocryptine (3H-DHE) appears to bind to two classes of sites with limited capacity, differing in their specificities and their affinities. The first class of binding sites interacts preferentially with the postsynaptic alpha-adrenoceptor blocker ARC239, as can be expected for postsynaptic alpha-adrenoceptors. The binding of 3H-DHE to these receptors follows the law of mass action, with a high affinity for 3H-DHE (Kd 25 degrees C = 1.67 +/- 0.37 nM). Postsynaptic saturating levels of 3H-DHE are necessary to occupy the second class of binding sites. These sites exhibit a preferential affinity for presynaptic ligands such as clonidine and yohimbine, as would be expected for presynaptic alpha-adrenergic receptors. This presynaptic binding shows a markedly positive homotropic cooperativity (Hill n = 2.88) with initial and final apparent Kds of 23 and 0.83 nM, respectively. Free energy of interaction between sites is of the order of 2 kcal (8.36 kJ)/mol of sites. These characteristics provide a rational molecular basis for the functional role of presynaptic alpha-adrenoceptors that mediate the inhibition of norepinephrine release from nerve endings.", "contents": "Biochemical evidence for presynaptic and postsynaptic alpha-adrenoceptors in rat heart membranes: positive homotropic cooperativity of presynaptic binding. In crude rat cardiac membrane preparations, [3H]dihydroergocryptine (3H-DHE) appears to bind to two classes of sites with limited capacity, differing in their specificities and their affinities. The first class of binding sites interacts preferentially with the postsynaptic alpha-adrenoceptor blocker ARC239, as can be expected for postsynaptic alpha-adrenoceptors. The binding of 3H-DHE to these receptors follows the law of mass action, with a high affinity for 3H-DHE (Kd 25 degrees C = 1.67 +/- 0.37 nM). Postsynaptic saturating levels of 3H-DHE are necessary to occupy the second class of binding sites. These sites exhibit a preferential affinity for presynaptic ligands such as clonidine and yohimbine, as would be expected for presynaptic alpha-adrenergic receptors. This presynaptic binding shows a markedly positive homotropic cooperativity (Hill n = 2.88) with initial and final apparent Kds of 23 and 0.83 nM, respectively. Free energy of interaction between sites is of the order of 2 kcal (8.36 kJ)/mol of sites. These characteristics provide a rational molecular basis for the functional role of presynaptic alpha-adrenoceptors that mediate the inhibition of norepinephrine release from nerve endings."}
{"id": "PMID:216020", "title": "Voltage-sensitive calcium channels regulate guanosine 3',5'-cyclic monophosphate levels in neuroblastoma cells.", "content": "Veratridine or high potassium concentration increased guanosine 3',5'-cyclic monophosphate (cGMP) levels in neuroblastoma cells of clone N1E-115 without affecting levels of adenosine 3',5'-cyclic monophosphate (cAMP). The increases in cGMP appear to be a direct result of the depolarizing action of these agents and not due to the action of substances released from the cells upon depolarization. The increase in cGMP produced by depolarization was dependent upon extracellular calcium and could be prevented by the calcium channel blockers D600 and cobalt. Carbachol, acting on muscarinic acetylcholine receptors, also caused a calcium-dependent increase in cGMP in these cells. The carbachol and potassium effects were additive from 5 to 100 mM potassium and from 1 to 3 mM calcium. The carbachol response was nearly as sensitive as the potassium response to inhibition by D600 but was much less sensitive to inhibition by cobalt. The results suggest that depolarization increases cGMP levels in these cells by opening voltage-sensitive calcium channels and that activation of muscarinic receptors opens separate, voltage-insensitive calcium channels.", "contents": "Voltage-sensitive calcium channels regulate guanosine 3',5'-cyclic monophosphate levels in neuroblastoma cells. Veratridine or high potassium concentration increased guanosine 3',5'-cyclic monophosphate (cGMP) levels in neuroblastoma cells of clone N1E-115 without affecting levels of adenosine 3',5'-cyclic monophosphate (cAMP). The increases in cGMP appear to be a direct result of the depolarizing action of these agents and not due to the action of substances released from the cells upon depolarization. The increase in cGMP produced by depolarization was dependent upon extracellular calcium and could be prevented by the calcium channel blockers D600 and cobalt. Carbachol, acting on muscarinic acetylcholine receptors, also caused a calcium-dependent increase in cGMP in these cells. The carbachol and potassium effects were additive from 5 to 100 mM potassium and from 1 to 3 mM calcium. The carbachol response was nearly as sensitive as the potassium response to inhibition by D600 but was much less sensitive to inhibition by cobalt. The results suggest that depolarization increases cGMP levels in these cells by opening voltage-sensitive calcium channels and that activation of muscarinic receptors opens separate, voltage-insensitive calcium channels."}
{"id": "PMID:216025", "title": "Pituitary-adrenal axis and oral morphine consumption in rats.", "content": "Removal of the pituitary gland in rats leads to suppression of oral morphine and quinine intake behavior. Experiments measuring oral intake of solutions containing graded concentrations of morphine or quinine, revealed that the detection acuity for bitter taste is changed in hypophysectomized (hypox) animals. Treatment of these rats with ACTH 1--24 restored oral morphine intake towards that on intact rats. Morphine consumption in hypox rats was not affected by administration of ACTH 4--10 or ACTH 11--24, but was normalized by treatment with corticosterone. Adrenalectomy also diminished oral morphine intake. It is concluded that hypophysectomized animals refuse a morphine solution because their threshold for bitter taste quality is altered, presumably due to a diminished release of corticosteroids.", "contents": "Pituitary-adrenal axis and oral morphine consumption in rats. Removal of the pituitary gland in rats leads to suppression of oral morphine and quinine intake behavior. Experiments measuring oral intake of solutions containing graded concentrations of morphine or quinine, revealed that the detection acuity for bitter taste is changed in hypophysectomized (hypox) animals. Treatment of these rats with ACTH 1--24 restored oral morphine intake towards that on intact rats. Morphine consumption in hypox rats was not affected by administration of ACTH 4--10 or ACTH 11--24, but was normalized by treatment with corticosterone. Adrenalectomy also diminished oral morphine intake. It is concluded that hypophysectomized animals refuse a morphine solution because their threshold for bitter taste quality is altered, presumably due to a diminished release of corticosteroids."}
{"id": "PMID:216026", "title": "Morphine self-administration and EEG power spectra in the rat.", "content": "Power spectral analyses were used to study changes in cortical EEG during morphine self-administration in freely-moving dependent rats prepared with chronic cortical and muscle electrodes and with permanent indwelling IV cannulae. As time progressed from a morphine self-injection toward another injection, a significant spectral shift of the EEG to lower frequencies occurred during successive REM sleep episodes. Each morphine self-injection reinstated the predominance of higher frequencies in the EEG spectra. These EEG changes which preceded lever pressing may reflect changes in morphine plasma levels and in the state of the CNS that precede drug-seeking behavior.", "contents": "Morphine self-administration and EEG power spectra in the rat. Power spectral analyses were used to study changes in cortical EEG during morphine self-administration in freely-moving dependent rats prepared with chronic cortical and muscle electrodes and with permanent indwelling IV cannulae. As time progressed from a morphine self-injection toward another injection, a significant spectral shift of the EEG to lower frequencies occurred during successive REM sleep episodes. Each morphine self-injection reinstated the predominance of higher frequencies in the EEG spectra. These EEG changes which preceded lever pressing may reflect changes in morphine plasma levels and in the state of the CNS that precede drug-seeking behavior."}
{"id": "PMID:216027", "title": "MSH/ACTH4-10 and task-induced increase in tendon reflexes and heart rate.", "content": "Earlier studies revealed that during a binary choice reaction task an increase of tendon reflex amplitudes and heart rate can be found, together with a suppression of heart rate variability. The results were interpreted as a task-induced increase in generalized arousal. In this study two experiments, consisting of a rest period and a binary choice reaction task, were done. In Experiment 1, twenty subjects, in a cross-over design, received 15 mg MSH/ACTH4-10 or a placebo. Only reflexes were recorded. In experiment 2, three groups of 9 subjects received either 30 or 15 mg MSH/ACTH4-10 or a placebo. Reflexes, heart rate and heart rate variability were recorded. Rest-task differences of reflexes and heart rate were enhanced by the drug. We hypothesized that MSH/ACTH4-10 intensified the arousal effect of the task.", "contents": "MSH/ACTH4-10 and task-induced increase in tendon reflexes and heart rate. Earlier studies revealed that during a binary choice reaction task an increase of tendon reflex amplitudes and heart rate can be found, together with a suppression of heart rate variability. The results were interpreted as a task-induced increase in generalized arousal. In this study two experiments, consisting of a rest period and a binary choice reaction task, were done. In Experiment 1, twenty subjects, in a cross-over design, received 15 mg MSH/ACTH4-10 or a placebo. Only reflexes were recorded. In experiment 2, three groups of 9 subjects received either 30 or 15 mg MSH/ACTH4-10 or a placebo. Reflexes, heart rate and heart rate variability were recorded. Rest-task differences of reflexes and heart rate were enhanced by the drug. We hypothesized that MSH/ACTH4-10 intensified the arousal effect of the task."}
{"id": "PMID:216043", "title": "The effects of prostaglandins on cAMP levels in subpopulations of mouse lymphocytes.", "content": "The effects of prostaglandin E2 (PGE2) on cyclic AMP levels in various mouse lymphocyte populations were studied. It was found that spleen cells and thymocytes respond comparably to PGE2. Cortisone treatment abolished the responsiveness in thymocytes. Fractionation of splenic lymphocytes on glass wool columns into subpopulations of bone-marrow derived (B) cells or thymus-derived (T) cells showed that both B and T splenic lymphocytes can respond to PGE2. Lymphocytes or spleen cells cultured for varying periods (24--96 hrs) lose their sensitivity to PGE2 stimulation of cAMP. This \"refractoriness\" to PGE2 is only partially reversed by incubating lymphocytes with phosphodiesterase inhibitors.", "contents": "The effects of prostaglandins on cAMP levels in subpopulations of mouse lymphocytes. The effects of prostaglandin E2 (PGE2) on cyclic AMP levels in various mouse lymphocyte populations were studied. It was found that spleen cells and thymocytes respond comparably to PGE2. Cortisone treatment abolished the responsiveness in thymocytes. Fractionation of splenic lymphocytes on glass wool columns into subpopulations of bone-marrow derived (B) cells or thymus-derived (T) cells showed that both B and T splenic lymphocytes can respond to PGE2. Lymphocytes or spleen cells cultured for varying periods (24--96 hrs) lose their sensitivity to PGE2 stimulation of cAMP. This \"refractoriness\" to PGE2 is only partially reversed by incubating lymphocytes with phosphodiesterase inhibitors."}
{"id": "PMID:216045", "title": "The relationship between changes in REM sleep and clinical improvement in depressed patients treated with amitriptyline.", "content": "EEG sleep recordings were obtained on consecutive nights from six hospitalized depressed patients before, during, and after treatment with amitriptyline for a total of 370 nights of data, about 85% of all nights of the study. Amitriptyline significantly reduced time spent in rapid eye movement (REM) sleep and prolonged the REM latency throughout the treatment period. Three patients who improved during treatment showed a REM rebound when amitriptyline was discontinued, whereas three patients who did not improve showed no REM rebound.", "contents": "The relationship between changes in REM sleep and clinical improvement in depressed patients treated with amitriptyline. EEG sleep recordings were obtained on consecutive nights from six hospitalized depressed patients before, during, and after treatment with amitriptyline for a total of 370 nights of data, about 85% of all nights of the study. Amitriptyline significantly reduced time spent in rapid eye movement (REM) sleep and prolonged the REM latency throughout the treatment period. Three patients who improved during treatment showed a REM rebound when amitriptyline was discontinued, whereas three patients who did not improve showed no REM rebound."}
{"id": "PMID:216046", "title": "Sustained ingestion of methadone and the sleep of monkeys.", "content": "Methadone HCl was administered daily to four stump-tailed macaques. The animals' sleep was periodically examined throughtout a year of methadone maintenance and, in two animals, during eight months of withdrawal. REM sleep was substantially decreased by methadone treatment and gradually returned to predrug values over a 6- to 8-month period of maintenance. Measures of non-REM sleep and awakenings showed similar disruption with no return to predrug values. These changes were not correlated with alterations in plasma-methadone concentrations. REM sleep rebound occurred temporarily upon drug withdrawal in two animals, but no consistent sleep disruption was apparent during the subsequent eight months. Contrary to some suggestions, therefore, tolerance to the sleep-disruptive effects of the drug may be specific and incomplete, and extended REM rebound upon withdrawal is not a universal response.", "contents": "Sustained ingestion of methadone and the sleep of monkeys. Methadone HCl was administered daily to four stump-tailed macaques. The animals' sleep was periodically examined throughtout a year of methadone maintenance and, in two animals, during eight months of withdrawal. REM sleep was substantially decreased by methadone treatment and gradually returned to predrug values over a 6- to 8-month period of maintenance. Measures of non-REM sleep and awakenings showed similar disruption with no return to predrug values. These changes were not correlated with alterations in plasma-methadone concentrations. REM sleep rebound occurred temporarily upon drug withdrawal in two animals, but no consistent sleep disruption was apparent during the subsequent eight months. Contrary to some suggestions, therefore, tolerance to the sleep-disruptive effects of the drug may be specific and incomplete, and extended REM rebound upon withdrawal is not a universal response."}
{"id": "PMID:216052", "title": "[The significance of sialography in tumors of the parotid gland (author's transl)].", "content": "The significance of sialography in diagnosis of parotid gland tumors is based on the differentiation of chronic inflammatory, benign and malignant lesions. This method combined with history and physical findings will establish the diagnosis in 80% of cases with parotid gland tumors. Water-soluble contrast media are most useful for ductography. It provides good contrast, stays in the duct system for a sufficient period of time and will not cause inconvenience to the patient. Tomograms are particularly valuable in addition to the standard a.p. and lateral standard views. Chronic inflammation causes alterations with small paraductal contrast accumulations throughout the entire efferent duct system. Benign tumors may be recognized by straight ducts and interlobular paravasates. In malignant neoplasms filling defects are more characteristic than parenchymal staining. Peracute and subacute inflammations as well as tuberculosis are difficult to diagnose by sialography.", "contents": "[The significance of sialography in tumors of the parotid gland (author's transl)]. The significance of sialography in diagnosis of parotid gland tumors is based on the differentiation of chronic inflammatory, benign and malignant lesions. This method combined with history and physical findings will establish the diagnosis in 80% of cases with parotid gland tumors. Water-soluble contrast media are most useful for ductography. It provides good contrast, stays in the duct system for a sufficient period of time and will not cause inconvenience to the patient. Tomograms are particularly valuable in addition to the standard a.p. and lateral standard views. Chronic inflammation causes alterations with small paraductal contrast accumulations throughout the entire efferent duct system. Benign tumors may be recognized by straight ducts and interlobular paravasates. In malignant neoplasms filling defects are more characteristic than parenchymal staining. Peracute and subacute inflammations as well as tuberculosis are difficult to diagnose by sialography."}
{"id": "PMID:216053", "title": "Computed tomography in the staging of testicular neoplasms.", "content": "Twenty-six patients with primary testicular tumor were evaluated by computed tomography. It was highly accurate in differentiating lymph node metastases from testicular tumors. CT scanning may reveal tumor in lymph nodes not normally opacified during bipedal lymphangiography. It can also be used in treatment planning, follow-up, and in localizing sites of recurrence when serum tumor markers become positive. Some pitfalls of CT are also discussed.", "contents": "Computed tomography in the staging of testicular neoplasms. Twenty-six patients with primary testicular tumor were evaluated by computed tomography. It was highly accurate in differentiating lymph node metastases from testicular tumors. CT scanning may reveal tumor in lymph nodes not normally opacified during bipedal lymphangiography. It can also be used in treatment planning, follow-up, and in localizing sites of recurrence when serum tumor markers become positive. Some pitfalls of CT are also discussed."}
{"id": "PMID:216054", "title": "A simple model for anatomic bone scanning studies.", "content": "A simple anatomic model for studying the scintigraphic appearance of various skeletal structures is described. The technique makes use of the fact that technitium pyrophosphate uptake in bone occurs by chemisorption to the surface of crystals in the bone matrix. By soaking clean bones in solutions of technetium pyrophosphate they can be rendered radioactive and subsequently studied by various imaging techniques.", "contents": "A simple model for anatomic bone scanning studies. A simple anatomic model for studying the scintigraphic appearance of various skeletal structures is described. The technique makes use of the fact that technitium pyrophosphate uptake in bone occurs by chemisorption to the surface of crystals in the bone matrix. By soaking clean bones in solutions of technetium pyrophosphate they can be rendered radioactive and subsequently studied by various imaging techniques."}
{"id": "PMID:216063", "title": "Regulation of beta-adrenergic response in human lymphocytes: agonist induced subsensitivity.", "content": "The concentration of intracellular cAMP in lymphocytes is regulated by isoproterenol and PGE1. Preincubation of lymphocytes with isoproterenol leads to a loss of the response to beta-adrenergic agents but not to PGE1. Preincubation of lymphocytes with PGE1, however, affects the sensitivities both to isoproterenol and PGE1. A decrease of beta-adrenergic receptors was found in cells preincubated with isoproterenol but not with PGE1. Part of the abnormalities associated with PGE1-preincubated cells can be restored by treating the cells with theophylline.", "contents": "Regulation of beta-adrenergic response in human lymphocytes: agonist induced subsensitivity. The concentration of intracellular cAMP in lymphocytes is regulated by isoproterenol and PGE1. Preincubation of lymphocytes with isoproterenol leads to a loss of the response to beta-adrenergic agents but not to PGE1. Preincubation of lymphocytes with PGE1, however, affects the sensitivities both to isoproterenol and PGE1. A decrease of beta-adrenergic receptors was found in cells preincubated with isoproterenol but not with PGE1. Part of the abnormalities associated with PGE1-preincubated cells can be restored by treating the cells with theophylline."}
{"id": "PMID:216064", "title": "Influence of inhibition of angiotensin I converting enzyme with SQ-14225 on the arterial blood pressure of mongrel dogs.", "content": "Effects of SQ-14225 (0.1, 0.3, and 3.0 mg/kg, i.v.) on the pressor responses to angiotensin I (A-I) and on the arterial blood pressure were investigated in anesthetized mongrel dogs. All the three doses significantly inhibited A-I induced pressor response (70-80%), however reduction in the blood pressure was noted only with the highest dose used. Neither bilateral nephrectomy, autonomic ganglionic blockade nor pretreatment with saralasin, an angiotensin II antagonist, altered the hypotensive activity of SQ-14225 (3 mg/kg, i.v.). The results of this study indicate that significant inhibition of angiotensin converting enzyme does not result in a decrease in the blood pressure in dogs, and that the hypotension produced by SQ-14225 may involve a mechanism yet to be identified.", "contents": "Influence of inhibition of angiotensin I converting enzyme with SQ-14225 on the arterial blood pressure of mongrel dogs. Effects of SQ-14225 (0.1, 0.3, and 3.0 mg/kg, i.v.) on the pressor responses to angiotensin I (A-I) and on the arterial blood pressure were investigated in anesthetized mongrel dogs. All the three doses significantly inhibited A-I induced pressor response (70-80%), however reduction in the blood pressure was noted only with the highest dose used. Neither bilateral nephrectomy, autonomic ganglionic blockade nor pretreatment with saralasin, an angiotensin II antagonist, altered the hypotensive activity of SQ-14225 (3 mg/kg, i.v.). The results of this study indicate that significant inhibition of angiotensin converting enzyme does not result in a decrease in the blood pressure in dogs, and that the hypotension produced by SQ-14225 may involve a mechanism yet to be identified."}
{"id": "PMID:216065", "title": "Reduction of methylmercury concentration in neonatal rat brains after administration of dimercaptosuccinic acid to dams while pregnant.", "content": "Sprague-Dawley rats were gavaged on day 7 of gestation with 1.62, 3.23 or 10 mg methylmercury/kg. Beginning one day later, the dams were administered 0, 20 or 40 mg 2,3-dimercaptosuccinic acid/kg/day until they delivered their pups. Concentrations of methylmercury in the brains of pups whose dams were treated with 20 mg DMSA/kg/day were reduced 50% compared with control pups. 40 mg DMSA/kg/day decreased brain concentrations 70% compared to non-chelated controls. The data indicate that DMSA might be effective in protecting the developing organism against morphological and/or behavioral teratological consequences of methylmercury poisoning in utero.", "contents": "Reduction of methylmercury concentration in neonatal rat brains after administration of dimercaptosuccinic acid to dams while pregnant. Sprague-Dawley rats were gavaged on day 7 of gestation with 1.62, 3.23 or 10 mg methylmercury/kg. Beginning one day later, the dams were administered 0, 20 or 40 mg 2,3-dimercaptosuccinic acid/kg/day until they delivered their pups. Concentrations of methylmercury in the brains of pups whose dams were treated with 20 mg DMSA/kg/day were reduced 50% compared with control pups. 40 mg DMSA/kg/day decreased brain concentrations 70% compared to non-chelated controls. The data indicate that DMSA might be effective in protecting the developing organism against morphological and/or behavioral teratological consequences of methylmercury poisoning in utero."}
{"id": "PMID:216066", "title": "The relative effectiveness of some chelating agents as antidotes in acute cadmium poisoning.", "content": "An examination has been made of the relative effectiveness of three chelating agents in reducing lethality in acute cadmium poisoning. The chelating agents used were sodium 2,3 dimercaptosulfonate (DMPS), N-Acetyl d,1 penicillamine (NAPA), and 2,3 dimercaptosuccinic acid (DMSA). For cadmium acetate administered ip at a level of 16.9 mg/kg, the oral administration of the chelating agents at a 20:1 mole ratio in three doses subsequent to the cadmium acetate at 20 minutes, 90 minutes, and 210 minutes resulted in a significant enhancement of the survival rate for all three compounds. At this level none of the control animals survived beyond 2 days. On the basis of the experiments carried out here the survival rates decreased in the order sodium 2,3 dimercaptopropane-sulfonate greater than 2,3 dimercaptosuccinic acid greater than N-Acetyl d,l penicillamine. In a study of the effect of the mole ratio of the chelating agent sodium 2,3 dimercaptopropanesulfonate to cadmium acetate on the survival rate, it was found that the survival rate attained a maximum for values between 20 and 60 and dropped off at both higher and lower values. It was also found that for at least one set of conditions, younger animals were better able to survive the administration of cadmium acetate and the antidote than older animals.", "contents": "The relative effectiveness of some chelating agents as antidotes in acute cadmium poisoning. An examination has been made of the relative effectiveness of three chelating agents in reducing lethality in acute cadmium poisoning. The chelating agents used were sodium 2,3 dimercaptosulfonate (DMPS), N-Acetyl d,1 penicillamine (NAPA), and 2,3 dimercaptosuccinic acid (DMSA). For cadmium acetate administered ip at a level of 16.9 mg/kg, the oral administration of the chelating agents at a 20:1 mole ratio in three doses subsequent to the cadmium acetate at 20 minutes, 90 minutes, and 210 minutes resulted in a significant enhancement of the survival rate for all three compounds. At this level none of the control animals survived beyond 2 days. On the basis of the experiments carried out here the survival rates decreased in the order sodium 2,3 dimercaptopropane-sulfonate greater than 2,3 dimercaptosuccinic acid greater than N-Acetyl d,l penicillamine. In a study of the effect of the mole ratio of the chelating agent sodium 2,3 dimercaptopropanesulfonate to cadmium acetate on the survival rate, it was found that the survival rate attained a maximum for values between 20 and 60 and dropped off at both higher and lower values. It was also found that for at least one set of conditions, younger animals were better able to survive the administration of cadmium acetate and the antidote than older animals."}
{"id": "PMID:216067", "title": "Selective action of hypoxia on rat lung cyclic AMP.", "content": "The effect of three different levels of 24-h hypobaric hypoxia (630 mm Hg, 520 mm Hg, and 340 mm Hg) on rat lung cAMP and cGMP was studied. Liver was also examined to evaluate comparatively with lung. Lung cAMP concentration averaged 33.6 +/- 2.2 (SE) pmol/mg protein, and cGMP averaged 2.4 +/- 0.21 (SE) pmol/mg protein. Twenty-four-hour hypoxia resulted in a significant 40% decrease in lung cAMP at 520 and 340 mm Hg. The magnitude of change was the same for both hypoxic levels suggesting threshold dependency. In contrast, liver cAMP was not affected by the hypoxic exposure. Lung and liver cGMP were also relatively refractory to hypoxia. The decreased cAMP concentration seen in the hypoxic lung returned to normal level within 24 hours. These data show that acute hypoxia has a selective action on lung cAMP.", "contents": "Selective action of hypoxia on rat lung cyclic AMP. The effect of three different levels of 24-h hypobaric hypoxia (630 mm Hg, 520 mm Hg, and 340 mm Hg) on rat lung cAMP and cGMP was studied. Liver was also examined to evaluate comparatively with lung. Lung cAMP concentration averaged 33.6 +/- 2.2 (SE) pmol/mg protein, and cGMP averaged 2.4 +/- 0.21 (SE) pmol/mg protein. Twenty-four-hour hypoxia resulted in a significant 40% decrease in lung cAMP at 520 and 340 mm Hg. The magnitude of change was the same for both hypoxic levels suggesting threshold dependency. In contrast, liver cAMP was not affected by the hypoxic exposure. Lung and liver cGMP were also relatively refractory to hypoxia. The decreased cAMP concentration seen in the hypoxic lung returned to normal level within 24 hours. These data show that acute hypoxia has a selective action on lung cAMP."}
{"id": "PMID:216071", "title": "A crucial factor in community program success: the extended psychosocial kinship system.", "content": "A crucial factor in community program success is the program's capacity to foster and strengthen an extended psychosocial network of neighbors, friends, and associates at work or school, as well as the extended kinship system. The chronically hospitalized patient and the young, isolated, acutely psychotic adult are both in need of an enhanced psychosocial system when entering a community program. The experience of Berkeley House, a psychiatric halfway house, is related as an example of a program that has achieved successful community tenure for its patients through the creation of an extended psychosocial kinship system. Four principal ways in which the system was sustained through the Berkeley House program are described: (1) through the ex-resident program; (2) through housing arrangements; (3) through work; and (4) through a variety of avocational and social groupings. The extended psychosocial matrix formed by overlapping groups is illustrated.", "contents": "A crucial factor in community program success: the extended psychosocial kinship system. A crucial factor in community program success is the program's capacity to foster and strengthen an extended psychosocial network of neighbors, friends, and associates at work or school, as well as the extended kinship system. The chronically hospitalized patient and the young, isolated, acutely psychotic adult are both in need of an enhanced psychosocial system when entering a community program. The experience of Berkeley House, a psychiatric halfway house, is related as an example of a program that has achieved successful community tenure for its patients through the creation of an extended psychosocial kinship system. Four principal ways in which the system was sustained through the Berkeley House program are described: (1) through the ex-resident program; (2) through housing arrangements; (3) through work; and (4) through a variety of avocational and social groupings. The extended psychosocial matrix formed by overlapping groups is illustrated."}
{"id": "PMID:216072", "title": "Psychiatric rehabilitation and long-term rehospitalization rates: the findings of two research studies.", "content": "Two controlled studies at Fountain House examined the influence of psychiatric rehabilitation services on rehospitalization. Study I, initiated in 1959, followed 252 experimental and 81 control subjects for 9 years. Study II, initiated in 1964, followed 40 experimental and 34 control subjects for 5 years. Experimental subjects had Fountain House services available, while controls did not. Additionally, experimental subgroups received systematic reaching-out services: home visits, telephone or letter contact. Study II findings essentially replicated study I. Followup was 96--97 percent complete. Three quarters of controls were rehospitalized within 5 years. Experimental subjects receiving reaching-out services for 2 years had significantly lower rehospitalization rates for the first 5 years in study I and the first 2 years in study II. Rehospitalizations were delayed, not prevented. Study I experimentals receiving 2 years of reaching-out services spent twice as long in the community before rehospitalization and 40 percent fewer days in the hospital than controls. Study II experimental subjects were in the community almost three times longer than controls before rehospitalization. Half of study I experimental subjects attended less than 10 times. Experimental subjects receiving reaching-out services attended twice as often as those not receiving reaching-out services. Low or nonattending experimentals had almost identical relapse rates (77 percent) as controls (74 percent), while, of experimentals having 100 or more visits, 37 percent were rehospitalized.", "contents": "Psychiatric rehabilitation and long-term rehospitalization rates: the findings of two research studies. Two controlled studies at Fountain House examined the influence of psychiatric rehabilitation services on rehospitalization. Study I, initiated in 1959, followed 252 experimental and 81 control subjects for 9 years. Study II, initiated in 1964, followed 40 experimental and 34 control subjects for 5 years. Experimental subjects had Fountain House services available, while controls did not. Additionally, experimental subgroups received systematic reaching-out services: home visits, telephone or letter contact. Study II findings essentially replicated study I. Followup was 96--97 percent complete. Three quarters of controls were rehospitalized within 5 years. Experimental subjects receiving reaching-out services for 2 years had significantly lower rehospitalization rates for the first 5 years in study I and the first 2 years in study II. Rehospitalizations were delayed, not prevented. Study I experimentals receiving 2 years of reaching-out services spent twice as long in the community before rehospitalization and 40 percent fewer days in the hospital than controls. Study II experimental subjects were in the community almost three times longer than controls before rehospitalization. Half of study I experimental subjects attended less than 10 times. Experimental subjects receiving reaching-out services attended twice as often as those not receiving reaching-out services. Low or nonattending experimentals had almost identical relapse rates (77 percent) as controls (74 percent), while, of experimentals having 100 or more visits, 37 percent were rehospitalized."}
{"id": "PMID:216073", "title": "Intracerebral adrenocorticotropic hormone mediates novelty-induced grooming in the rat.", "content": "Intact male rats exhibited more grooming in unfamiliar testing chambers than in their home cages. Hypophysectomized rats showed a much reduced increase in grooming in these testing chambers. Intraventricular injections of antiserum to adrenocorticotropic hormone to intact rats decreased the grooming usually observed in the novel situation, whereas a similar injection of control serum did not produce this effect. Peripheral injections of the antiserum did not affect grooming. Since intraventricularly injected adrenocorticotropic hormone induces excessive grooming, these results suggest that the increased grooming observed in the novel environment may be at least partly due to the release of this hormone directly into the cerebral ventricular system.", "contents": "Intracerebral adrenocorticotropic hormone mediates novelty-induced grooming in the rat. Intact male rats exhibited more grooming in unfamiliar testing chambers than in their home cages. Hypophysectomized rats showed a much reduced increase in grooming in these testing chambers. Intraventricular injections of antiserum to adrenocorticotropic hormone to intact rats decreased the grooming usually observed in the novel situation, whereas a similar injection of control serum did not produce this effect. Peripheral injections of the antiserum did not affect grooming. Since intraventricularly injected adrenocorticotropic hormone induces excessive grooming, these results suggest that the increased grooming observed in the novel environment may be at least partly due to the release of this hormone directly into the cerebral ventricular system."}
{"id": "PMID:216070", "title": "Hepatocellular carcinoma (an approach to the study of risk factors in human cancer).", "content": "Risk factors can be used to formulate hypotheses on the aetiology and pathogenesis of site specific cancers. Persistent infection with hepatitis B virus (HBV), chronic liver disease, and maleness are associated with a greatly increased risk of developing primary hepatocellular carcinoma (PHC). A model for the pathogenesis of this tumour is proposed that does not involve integration of the HBV genome into the tumour cell. If chronic infection with HBV is necessary for the development of chronic liver disease and PHC, prevention of PHC could be accomplished by prevention of infection with HBV. A vaccine against HBV could be accomplished by prevention of infection with HBV. A vaccine against HBV has been developed; if it is effective, we can predict that its use in endemic areas will be accompanied by an eventual fall in the incidence of PHC.", "contents": "Hepatocellular carcinoma (an approach to the study of risk factors in human cancer). Risk factors can be used to formulate hypotheses on the aetiology and pathogenesis of site specific cancers. Persistent infection with hepatitis B virus (HBV), chronic liver disease, and maleness are associated with a greatly increased risk of developing primary hepatocellular carcinoma (PHC). A model for the pathogenesis of this tumour is proposed that does not involve integration of the HBV genome into the tumour cell. If chronic infection with HBV is necessary for the development of chronic liver disease and PHC, prevention of PHC could be accomplished by prevention of infection with HBV. A vaccine against HBV could be accomplished by prevention of infection with HBV. A vaccine against HBV has been developed; if it is effective, we can predict that its use in endemic areas will be accompanied by an eventual fall in the incidence of PHC."}
{"id": "PMID:216075", "title": "Lithium: a modulator of cyclic AMP-dependent events in lymphocytes?", "content": "Theophylline, salbutamol, isoproterenol, and dibutyryl cyclic AMP inhibited E-rosette formation by human T lymphocytes and immunoglobulin M secretion from human plaque-forming B cells and augmented T-suppressor cell activity in three patients with agammaglobulinemia. Lithium chloride increased mitogen-induced lymphocyte proliferation and inhibited suppressor cell activity. In the presence of lithium, the effects of all the drugs except dibutyryl cyclic AMP could be prevented. The data suggest a role for lithium in the modulation of cyclic AMP-dependent events in lymphocytes. Its potential role as an inhibitor of suppressor cell activity warrants further attention.", "contents": "Lithium: a modulator of cyclic AMP-dependent events in lymphocytes? Theophylline, salbutamol, isoproterenol, and dibutyryl cyclic AMP inhibited E-rosette formation by human T lymphocytes and immunoglobulin M secretion from human plaque-forming B cells and augmented T-suppressor cell activity in three patients with agammaglobulinemia. Lithium chloride increased mitogen-induced lymphocyte proliferation and inhibited suppressor cell activity. In the presence of lithium, the effects of all the drugs except dibutyryl cyclic AMP could be prevented. The data suggest a role for lithium in the modulation of cyclic AMP-dependent events in lymphocytes. Its potential role as an inhibitor of suppressor cell activity warrants further attention."}
{"id": "PMID:216076", "title": "Cloning of herpes simplex type 1 DNA fragments in a bacteriophage lambda vector.", "content": "DNA isolated from defective and nondefective virions of herpes simplex type 1 (HSV-1) (strain Patton) was digested with restriction endonucleases, and the resulting DNA fragments were inserted in the EK2 coliphage vector lambdagtWES . lambdaB. The recombinant DNA was encapsidated in vitro under P4 maximum containment conditions. These lambda-HSV1 hybrids were purified and amplified, and the DNA was isolated in the P4 facility. DNA, free of viable phage and bacteria, was removed from P4 conditions and analyzed. Represented among the hybrids studied to date are DNA fragments from about 50 percent of the normal HSV-1 genome. The hybrids derived from defective HSV-1 DNA fragments demonstrate the existence of many similar but not identical classes of defective genomes.", "contents": "Cloning of herpes simplex type 1 DNA fragments in a bacteriophage lambda vector. DNA isolated from defective and nondefective virions of herpes simplex type 1 (HSV-1) (strain Patton) was digested with restriction endonucleases, and the resulting DNA fragments were inserted in the EK2 coliphage vector lambdagtWES . lambdaB. The recombinant DNA was encapsidated in vitro under P4 maximum containment conditions. These lambda-HSV1 hybrids were purified and amplified, and the DNA was isolated in the P4 facility. DNA, free of viable phage and bacteria, was removed from P4 conditions and analyzed. Represented among the hybrids studied to date are DNA fragments from about 50 percent of the normal HSV-1 genome. The hybrids derived from defective HSV-1 DNA fragments demonstrate the existence of many similar but not identical classes of defective genomes."}
{"id": "PMID:216077", "title": "Rotaviral immunity in gnotobiotic calves: heterologous resistance to human virus induced by bovine virus.", "content": "The possibility of immunizing human infants against rotaviruses, which cause severe dehydrating diarrheal disease, may depend on the use of a related rotavirus, derived from another animal species, as a source of antigen. To test the feasibility of this approach, calves were infected in utero with a bovine rotavirus and challenged with bovine or human type 2 rotavirus shortly after birth. Infection in utero with bovine rotavirus induced resistance to diarrheal disease caused by the human virus as well as the homologous bovine virus. These data suggest that the bovine virus is sufficiently related antigenically to the human type 2 virus to warrant further evaluation of the former as a source of vaccine.", "contents": "Rotaviral immunity in gnotobiotic calves: heterologous resistance to human virus induced by bovine virus. The possibility of immunizing human infants against rotaviruses, which cause severe dehydrating diarrheal disease, may depend on the use of a related rotavirus, derived from another animal species, as a source of antigen. To test the feasibility of this approach, calves were infected in utero with a bovine rotavirus and challenged with bovine or human type 2 rotavirus shortly after birth. Infection in utero with bovine rotavirus induced resistance to diarrheal disease caused by the human virus as well as the homologous bovine virus. These data suggest that the bovine virus is sufficiently related antigenically to the human type 2 virus to warrant further evaluation of the former as a source of vaccine."}
{"id": "PMID:216079", "title": "[Importance of endoscopy with biopsy in gastroduodenal amyloidosis. Apropos of 5 cases].", "content": "The authors report five cases of gastric amyloidosis in addition of the fourty three published cases. These cases was polyvisceral forms, 4 times primitive and 1 time secondary to a psoriasic rheumatism. Three times only the patients had complaints of digestive tract. Four times non specific radiologic and endoscopic signs lead to a biopsy which permits diagnosis. The biopsy of gastric mucosa must take place beside the rectal biopsy; more difficult to do, it might be more successfull because the stomach is more often infiltrated by amyloidosis than the colon.", "contents": "[Importance of endoscopy with biopsy in gastroduodenal amyloidosis. Apropos of 5 cases]. The authors report five cases of gastric amyloidosis in addition of the fourty three published cases. These cases was polyvisceral forms, 4 times primitive and 1 time secondary to a psoriasic rheumatism. Three times only the patients had complaints of digestive tract. Four times non specific radiologic and endoscopic signs lead to a biopsy which permits diagnosis. The biopsy of gastric mucosa must take place beside the rectal biopsy; more difficult to do, it might be more successfull because the stomach is more often infiltrated by amyloidosis than the colon."}
{"id": "PMID:216081", "title": "[Intravenous nitroglycerin as vasodilator therapy in acute myocardial infarction (author's transl)].", "content": "Thirteen patients with left ventricular failure complicating acute myocardial infarction were treated with intravenous nitroglycerin. The hemodynamic criterium for admission to this study was a pulmonary capillary wedge pressure greater than 15 mm Hg. All patients received intravenous nitroglycerin at infusion rates sufficient to lower pulmonary capillary wedge pressure by an average of 15 mm Hg, corresponding to the optimal left ventricular filling pressure in acute myocardial infarction. During this study, heart rate did not vary significantly; pulmonary capillary wedge pressure decreased from 24 +/- 0,7 to 15 +/- 0,8 mm Hg (p less than 0,001), mean arterial pressure from 95 +/- 5 to 80 +/- 4 mm Hg (p less than 0,005), mean right atrium pressure from 8,7 +/- 1 to 4,6 +/- 0,8 mm Hg (p less than 0,001), systemic vascular resistance index from 36,4 +/- 2 to 29,6 +/- 2 mm Hg/mm-1/l/m2 (p less than 0,005). Cardiac index increased from 2,5 +/- 0,2 to 2,7 +/- 0,1 l/mn/m2 (p less than 0,025) and stroke work index did not vary significantly. These data indicate that nitroglycerin provides a significant improvement of cardiac performance, more through reduction of preload than through reduction of afterload, the later being however significant. This study points out that intravenous nitroglycerin is a most efficient drug in patients with left ventricular failure complicating acute myocardial infarction.", "contents": "[Intravenous nitroglycerin as vasodilator therapy in acute myocardial infarction (author's transl)]. Thirteen patients with left ventricular failure complicating acute myocardial infarction were treated with intravenous nitroglycerin. The hemodynamic criterium for admission to this study was a pulmonary capillary wedge pressure greater than 15 mm Hg. All patients received intravenous nitroglycerin at infusion rates sufficient to lower pulmonary capillary wedge pressure by an average of 15 mm Hg, corresponding to the optimal left ventricular filling pressure in acute myocardial infarction. During this study, heart rate did not vary significantly; pulmonary capillary wedge pressure decreased from 24 +/- 0,7 to 15 +/- 0,8 mm Hg (p less than 0,001), mean arterial pressure from 95 +/- 5 to 80 +/- 4 mm Hg (p less than 0,005), mean right atrium pressure from 8,7 +/- 1 to 4,6 +/- 0,8 mm Hg (p less than 0,001), systemic vascular resistance index from 36,4 +/- 2 to 29,6 +/- 2 mm Hg/mm-1/l/m2 (p less than 0,005). Cardiac index increased from 2,5 +/- 0,2 to 2,7 +/- 0,1 l/mn/m2 (p less than 0,025) and stroke work index did not vary significantly. These data indicate that nitroglycerin provides a significant improvement of cardiac performance, more through reduction of preload than through reduction of afterload, the later being however significant. This study points out that intravenous nitroglycerin is a most efficient drug in patients with left ventricular failure complicating acute myocardial infarction."}
{"id": "PMID:216080", "title": "[Calcitonin and hypercalcaemia (author's transl)].", "content": "We have discussed in an earlier paper the value of estimating the circulating levels of biologically active parathyroid hormone. We consider here the importance of an evaluation of circulating calcitonin by showing the frequency of raised calcitonin secretion in hypercalcaemia of different origins. These results lead one to attribute to calcitonin a role which goes beyond the regulation of phospho-calcium metabolism and which in fact is that of a particularly sensitive indicator of tumours.", "contents": "[Calcitonin and hypercalcaemia (author's transl)]. We have discussed in an earlier paper the value of estimating the circulating levels of biologically active parathyroid hormone. We consider here the importance of an evaluation of circulating calcitonin by showing the frequency of raised calcitonin secretion in hypercalcaemia of different origins. These results lead one to attribute to calcitonin a role which goes beyond the regulation of phospho-calcium metabolism and which in fact is that of a particularly sensitive indicator of tumours."}
{"id": "PMID:216083", "title": "[Hypotensive effects of timolol in 86 patients (author's transl)].", "content": "Antihypertensive action of timolol (MK 950) was studied in 86 outpatients with essential, uncomplicated hypertension. Timolol is an effective hypotensive drug with significant lowering pressor effect. Timolol was given alone in 53 cases and in association with other hypotensive drugs in 33 cases: the mean dose was 20 mg daily for 8 months. At the end of treatment the mean diastolic pressure recumbert, standing, and after exercise had decreased by 10.2, 9.2 and 11 mmHg. Cardiac frequency had decreased by 13, 24 and 29 p. min lying, standing and after exercise. Side effects were rare, with cessation of treatment only in 4 cases.", "contents": "[Hypotensive effects of timolol in 86 patients (author's transl)]. Antihypertensive action of timolol (MK 950) was studied in 86 outpatients with essential, uncomplicated hypertension. Timolol is an effective hypotensive drug with significant lowering pressor effect. Timolol was given alone in 53 cases and in association with other hypotensive drugs in 33 cases: the mean dose was 20 mg daily for 8 months. At the end of treatment the mean diastolic pressure recumbert, standing, and after exercise had decreased by 10.2, 9.2 and 11 mmHg. Cardiac frequency had decreased by 13, 24 and 29 p. min lying, standing and after exercise. Side effects were rare, with cessation of treatment only in 4 cases."}
{"id": "PMID:216082", "title": "[Study of rapidity of hypotensive effects of acebutolol on non hospitalized patients (author's transl)].", "content": "Acebutolol whose hypotensive properties are well established, appears as a most interesting beta-adrenergic blocking agent for simplification of treatment of moderate hypertension in man. Hypertensive patients likely to benefit from treatment with acebutolol can be identified within 5 days after administration of a single initial dose of the product. Long-term treatment with acebutolol can be considered in those patients identified as receptive. In non-responders, acebutolol can be used in combination with a diuretic agent. Such simplification of the therapeutic schedule in hypertension will certainly be helpfull both to the physician and his patient.", "contents": "[Study of rapidity of hypotensive effects of acebutolol on non hospitalized patients (author's transl)]. Acebutolol whose hypotensive properties are well established, appears as a most interesting beta-adrenergic blocking agent for simplification of treatment of moderate hypertension in man. Hypertensive patients likely to benefit from treatment with acebutolol can be identified within 5 days after administration of a single initial dose of the product. Long-term treatment with acebutolol can be considered in those patients identified as receptive. In non-responders, acebutolol can be used in combination with a diuretic agent. Such simplification of the therapeutic schedule in hypertension will certainly be helpfull both to the physician and his patient."}
{"id": "PMID:216087", "title": "[Comparative study of antiarrhythmic properties of quinicine versus quinidine (author's transl)].", "content": "Quinicine, an isomer of quinidine is used for its cerebral vasodilating activity. This study was performed in order to find out if quinicine also behaves like an antiarrhythmic agent in animals. The preventive and curative actions of quinicine on the experimental ouabain induced arrhythmia have been demonstrated. The mechanism of action of this drug seems to be the same as quinidine, i.e. prolongation of refractory period, diminution of atrial and atrioventricular conduction velocities, anticholinergic and local anaesthesic properties. The quinuclidic ring is therefore not a major factor to assure the antiarrhythmic activity of quinquina alkaloids.", "contents": "[Comparative study of antiarrhythmic properties of quinicine versus quinidine (author's transl)]. Quinicine, an isomer of quinidine is used for its cerebral vasodilating activity. This study was performed in order to find out if quinicine also behaves like an antiarrhythmic agent in animals. The preventive and curative actions of quinicine on the experimental ouabain induced arrhythmia have been demonstrated. The mechanism of action of this drug seems to be the same as quinidine, i.e. prolongation of refractory period, diminution of atrial and atrioventricular conduction velocities, anticholinergic and local anaesthesic properties. The quinuclidic ring is therefore not a major factor to assure the antiarrhythmic activity of quinquina alkaloids."}
{"id": "PMID:216088", "title": "[Acute gastric and duodenal distress lesions. Circumstances of appearance, endoscopic detection. Treatment].", "content": "Upper digestive hemorrhages in patients in a state of distress have been known for some time whether the stress if of surgical of medical origin. Emergency gastroscopy is of great interest in the field of diagnosis and operative indications. As regards treatment one should emphasise the interest of prevention. As for the treatment of hemorrhage, it should first be medical and cimetidine gives at present the best results. Surgical treatment remains however indicated in a certain number of cases. The choice of operation is still debatable.", "contents": "[Acute gastric and duodenal distress lesions. Circumstances of appearance, endoscopic detection. Treatment]. Upper digestive hemorrhages in patients in a state of distress have been known for some time whether the stress if of surgical of medical origin. Emergency gastroscopy is of great interest in the field of diagnosis and operative indications. As regards treatment one should emphasise the interest of prevention. As for the treatment of hemorrhage, it should first be medical and cimetidine gives at present the best results. Surgical treatment remains however indicated in a certain number of cases. The choice of operation is still debatable."}
{"id": "PMID:216084", "title": "[Dysglobulinemic neuropathy. Apropos of IgD myeloma manifested by mononeuritis].", "content": "The authors report a case of IgD myeloma of which the initial symptom was a mononeuritis and the biological, immunological and ultrastructural study performed about this case. Then are reviewed the mechanisms, proved or hypothetical, by which are actually explained the event of neuropathies within lympho-plasmocytic disorders.", "contents": "[Dysglobulinemic neuropathy. Apropos of IgD myeloma manifested by mononeuritis]. The authors report a case of IgD myeloma of which the initial symptom was a mononeuritis and the biological, immunological and ultrastructural study performed about this case. Then are reviewed the mechanisms, proved or hypothetical, by which are actually explained the event of neuropathies within lympho-plasmocytic disorders."}
{"id": "PMID:216086", "title": "[Very severe haemorrhages of the lower digestive tract. The value of emergency arteriography (author's transl)].", "content": "The authors report six cases of massive lower gastro-intestinal tract haemorrhage, diagnosed by angiography. They emphasize the value of angiography performed on an emergency basis. It is the most reliable diagnostic modality to know before surgery the precise localization of the bleeding point and sometimes its aetiology. The interest and the problems of therapeutic angiography are discussed.", "contents": "[Very severe haemorrhages of the lower digestive tract. The value of emergency arteriography (author's transl)]. The authors report six cases of massive lower gastro-intestinal tract haemorrhage, diagnosed by angiography. They emphasize the value of angiography performed on an emergency basis. It is the most reliable diagnostic modality to know before surgery the precise localization of the bleeding point and sometimes its aetiology. The interest and the problems of therapeutic angiography are discussed."}
{"id": "PMID:216090", "title": "[Selective IgA deficiency, DPH-treated epilepsy and polyarthritis (author's transl)].", "content": "A selected IgA deficiency was found in a 66 years old, DPH-treated epileptic female, suffering from polyarthritis. Familial survey brings information for genetic transmission of IgA decreased concentrations in her offspring, unrelated with HLA A, B, C system.", "contents": "[Selective IgA deficiency, DPH-treated epilepsy and polyarthritis (author's transl)]. A selected IgA deficiency was found in a 66 years old, DPH-treated epileptic female, suffering from polyarthritis. Familial survey brings information for genetic transmission of IgA decreased concentrations in her offspring, unrelated with HLA A, B, C system."}
{"id": "PMID:216089", "title": "[Is rheumatoid arthritis connected with a digestive tract parasitosis? (author's transl)].", "content": "The comparison of blood eosinophil counts and stool parasites in two groups of patients--twenty one suffering from rheumatoid arthritis and twenty one from other various diseases--did not show any significant difference in favour of a parasitological etiology in rheumatoid arthritis, an hypothesis which had to be considered because of the efficacy of levamisole in the treatment of this disease.", "contents": "[Is rheumatoid arthritis connected with a digestive tract parasitosis? (author's transl)]. The comparison of blood eosinophil counts and stool parasites in two groups of patients--twenty one suffering from rheumatoid arthritis and twenty one from other various diseases--did not show any significant difference in favour of a parasitological etiology in rheumatoid arthritis, an hypothesis which had to be considered because of the efficacy of levamisole in the treatment of this disease."}
{"id": "PMID:216091", "title": "[Report of a case of Gaucher's disease in adult].", "content": "The authors report a case of Gaucher's disease in an adult. This is a rare disease due to the accumulation of a glucoceramide in the reticulo-endothelial cells and may remain for long clinically symptomless, as in this case. The diagnosis suggested by the biological disturbance, viz. moderate thrombopenia, hypergammaglobulinemia, increase in SGPT, was conformed by the presence of Gaucher's cells in the liver and in the bone marrow, and by the existence of an intraleukocytic glucosidase deficiency. The authors recall the clinical forms of this disease, and recent clinical trials.", "contents": "[Report of a case of Gaucher's disease in adult]. The authors report a case of Gaucher's disease in an adult. This is a rare disease due to the accumulation of a glucoceramide in the reticulo-endothelial cells and may remain for long clinically symptomless, as in this case. The diagnosis suggested by the biological disturbance, viz. moderate thrombopenia, hypergammaglobulinemia, increase in SGPT, was conformed by the presence of Gaucher's cells in the liver and in the bone marrow, and by the existence of an intraleukocytic glucosidase deficiency. The authors recall the clinical forms of this disease, and recent clinical trials."}
{"id": "PMID:216093", "title": "[Cefoxitin, a new semi-synthetic cephamycin (author's transl)].", "content": "The authors review the procedure utilized for the naming of a new antibiotic. The cephamycins are taken as an example. Cefoxitin, derivative of the cephamycin C through an original chemical reaction is described. This antibiotic possesses a high degree of resistance to beta-lactamases due to the presence of a methoxy group in the 7alpha position of the beta-lactam ring. The results of extensive in-vitro trials are given, they indicate that cefoxitin has a unique antibacterial activity.", "contents": "[Cefoxitin, a new semi-synthetic cephamycin (author's transl)]. The authors review the procedure utilized for the naming of a new antibiotic. The cephamycins are taken as an example. Cefoxitin, derivative of the cephamycin C through an original chemical reaction is described. This antibiotic possesses a high degree of resistance to beta-lactamases due to the presence of a methoxy group in the 7alpha position of the beta-lactam ring. The results of extensive in-vitro trials are given, they indicate that cefoxitin has a unique antibacterial activity."}
{"id": "PMID:216092", "title": "[Amyloid tumors of the lung. Apropos of a new case].", "content": "The authors report a new case of pseudo-tumoral nodular amyloidosis of the lungs. The amyloid nodules being discovered during a surgical procedure for an adenocarcinoma of the lower oesophagus. The histopathological study of the nodules confirmed their amyloid origin and allowed to precise their histochemical features.", "contents": "[Amyloid tumors of the lung. Apropos of a new case]. The authors report a new case of pseudo-tumoral nodular amyloidosis of the lungs. The amyloid nodules being discovered during a surgical procedure for an adenocarcinoma of the lower oesophagus. The histopathological study of the nodules confirmed their amyloid origin and allowed to precise their histochemical features."}
{"id": "PMID:216096", "title": "[Long term administration of oral prednisone or prednisolone in treatment of myasthenia gravis. Report of five cases (author's transl)].", "content": "Five patients, four of them with severe or severe generalized myasthenia gravis, were treated by long term orally administrated prednisolone, with following results: one complete remission and two almost complete remissions (in three aged fernale patients), two substantial improvements (one in a male patient, one in a young adult female patient, both thymectomized). The least favourable result was observed in the male patient. Positive results of such treatment were similarly reported by several authors (with an average of 70% complete or almost complete remission, 20% substantial improvement, 7% moderate improvement). These results appear qualitatively superior to those obtained with ACTH, and may be long-lasting. Treatment with prednisolone may be applied to any form of myasthenia gravis, particularly those which do not react to anticholinesterasic agents in moderate dosages. At onset of treatment, patients should be under care of a reanimation unit. Dosage is initially high (60--100 mg daily, secondarily on alternate days), and should be reduced very slowly, once a definite improvement is achieved. The duration of this treatment depends upon the results obtained: it should not last under one year. Associated treatment with anticholinesterasic agents remains disputable, whereas associated thymectomy seems to provide best results.", "contents": "[Long term administration of oral prednisone or prednisolone in treatment of myasthenia gravis. Report of five cases (author's transl)]. Five patients, four of them with severe or severe generalized myasthenia gravis, were treated by long term orally administrated prednisolone, with following results: one complete remission and two almost complete remissions (in three aged fernale patients), two substantial improvements (one in a male patient, one in a young adult female patient, both thymectomized). The least favourable result was observed in the male patient. Positive results of such treatment were similarly reported by several authors (with an average of 70% complete or almost complete remission, 20% substantial improvement, 7% moderate improvement). These results appear qualitatively superior to those obtained with ACTH, and may be long-lasting. Treatment with prednisolone may be applied to any form of myasthenia gravis, particularly those which do not react to anticholinesterasic agents in moderate dosages. At onset of treatment, patients should be under care of a reanimation unit. Dosage is initially high (60--100 mg daily, secondarily on alternate days), and should be reduced very slowly, once a definite improvement is achieved. The duration of this treatment depends upon the results obtained: it should not last under one year. Associated treatment with anticholinesterasic agents remains disputable, whereas associated thymectomy seems to provide best results."}
{"id": "PMID:216095", "title": "[Indication and problems of radiotherapy of primary bone and cartilage tumours of the thoracic wall (author's transl)].", "content": "The authors discuss the management in radiotherapy of bony tumours of the thoracic wall: necessity of accepting the risk due to the volume of healthy tissue which is inevitably irradiated, the technics of irradiation which limit these risks. Limited hope of improvement of the still modest results with new technics of radiotherapy. They emphasize the difference which exists between the idea of radiosensitivity and radiocurability.", "contents": "[Indication and problems of radiotherapy of primary bone and cartilage tumours of the thoracic wall (author's transl)]. The authors discuss the management in radiotherapy of bony tumours of the thoracic wall: necessity of accepting the risk due to the volume of healthy tissue which is inevitably irradiated, the technics of irradiation which limit these risks. Limited hope of improvement of the still modest results with new technics of radiotherapy. They emphasize the difference which exists between the idea of radiosensitivity and radiocurability."}
{"id": "PMID:216094", "title": "[Comparative clinical evaluation of two mucolytic agents: S-carboxy-methyl-cysteine and letosteine (author's transl)].", "content": "A controlled double-blind clinical trial comparing a noval medicament, letosteine, to a known bronchial fluidifier, S-carboxy-methyl-cysteine, was conducted on a total of 47 hospitalized patients suffering from various types of chronic obstructive lung disease. Daily observations were made on the patients themselves and on sputum samples obtained from them before, during and after the course of mucolytic therapy. When the code was broken at the end of the trial, there appeared no significant difference between the patient groups treated with the two drugs regarding either changes in respiratory symptoms or changes in sputum characteristics. Thus, in this study, letosteine (50 mg t.i.d.) appeared equivalent to S-carboxy-methyl-cysteine (750 mg t.i.d.) in the treatment of chronic obstructive lung disease in adults.", "contents": "[Comparative clinical evaluation of two mucolytic agents: S-carboxy-methyl-cysteine and letosteine (author's transl)]. A controlled double-blind clinical trial comparing a noval medicament, letosteine, to a known bronchial fluidifier, S-carboxy-methyl-cysteine, was conducted on a total of 47 hospitalized patients suffering from various types of chronic obstructive lung disease. Daily observations were made on the patients themselves and on sputum samples obtained from them before, during and after the course of mucolytic therapy. When the code was broken at the end of the trial, there appeared no significant difference between the patient groups treated with the two drugs regarding either changes in respiratory symptoms or changes in sputum characteristics. Thus, in this study, letosteine (50 mg t.i.d.) appeared equivalent to S-carboxy-methyl-cysteine (750 mg t.i.d.) in the treatment of chronic obstructive lung disease in adults."}
{"id": "PMID:216098", "title": "[Plexus lesions following radiation therapy. Report of nineteen cases (author's transl)].", "content": "Nineteen patients with plexus lesions following radiation therapy were investigated: fifteen with brachial plexus, 4 with lumbar or sacral plexus involvement. Symptoms at onset are usually sensory. Motor disturbances occur either simultaneously or after some delay, their course is generally gradual and unfavourable. Areflexia appears early and was present in every case. Important cutaneous lesions (radiodermitis) and considerable induration of soft tissues were observed in every patient. Diagnosis is a relapse of the mitotic process. Severity of prognosis makes imperative a definite technique of radiation therapy. In all the patients included in this study, dosage had exceded 1,600 rets. Patients were tentatively treated with D-penicillamine, an inhibitor of collagen synthesis.", "contents": "[Plexus lesions following radiation therapy. Report of nineteen cases (author's transl)]. Nineteen patients with plexus lesions following radiation therapy were investigated: fifteen with brachial plexus, 4 with lumbar or sacral plexus involvement. Symptoms at onset are usually sensory. Motor disturbances occur either simultaneously or after some delay, their course is generally gradual and unfavourable. Areflexia appears early and was present in every case. Important cutaneous lesions (radiodermitis) and considerable induration of soft tissues were observed in every patient. Diagnosis is a relapse of the mitotic process. Severity of prognosis makes imperative a definite technique of radiation therapy. In all the patients included in this study, dosage had exceded 1,600 rets. Patients were tentatively treated with D-penicillamine, an inhibitor of collagen synthesis."}
{"id": "PMID:216097", "title": "[Cisterno-medullary anomalies. Diagnostic problems, surgical treatment (author's transl)].", "content": "Under the term cisterno-medullary anomalies are included several disorders: bony and nervous malformations, arachnoiditis of the posterior fossa. As they are frequently associated, a thorough investigation, both anatomical and dynamic, is a prerequisite to any therapeutic attempt. Along with causing damage to the neuraxis, these anomalies interfere with the dynamics of the CSF and may lead to the development of a communicating syringomyelia, whatever the theory proposed. The presenting symptoms are varied, and diagnosis should be accordingly suspected. Of fundamental importance are instrumental investigations. A complete evaluation is in most of the cases obtainable with: bone X-rays, air-myelography (or \"bulle\"), intrathecal ou ventricular radio-isotope scan. Surgery is the only treatment. The aim is both decompression of the neural structures and restoration of a normal CSF dynamic flow. Opening of the posterior fossa is successful in the case of developmental abnormalities, But it seems to prove a failure when the chief anomaly is arachnoiditis. In such cases, ventricular drainage alone may be followed by improvement. It appears from this that the problem is twofold: the technical problem of the drainage, and the pre-operatory diagnosis of a posterior fossa arachnoiditis.", "contents": "[Cisterno-medullary anomalies. Diagnostic problems, surgical treatment (author's transl)]. Under the term cisterno-medullary anomalies are included several disorders: bony and nervous malformations, arachnoiditis of the posterior fossa. As they are frequently associated, a thorough investigation, both anatomical and dynamic, is a prerequisite to any therapeutic attempt. Along with causing damage to the neuraxis, these anomalies interfere with the dynamics of the CSF and may lead to the development of a communicating syringomyelia, whatever the theory proposed. The presenting symptoms are varied, and diagnosis should be accordingly suspected. Of fundamental importance are instrumental investigations. A complete evaluation is in most of the cases obtainable with: bone X-rays, air-myelography (or \"bulle\"), intrathecal ou ventricular radio-isotope scan. Surgery is the only treatment. The aim is both decompression of the neural structures and restoration of a normal CSF dynamic flow. Opening of the posterior fossa is successful in the case of developmental abnormalities, But it seems to prove a failure when the chief anomaly is arachnoiditis. In such cases, ventricular drainage alone may be followed by improvement. It appears from this that the problem is twofold: the technical problem of the drainage, and the pre-operatory diagnosis of a posterior fossa arachnoiditis."}
{"id": "PMID:216100", "title": "[The induced hyperlipemia test. 10 years of experience].", "content": "The induced hyperlipemia test, which is easly to administer, yields very interesting information for the study of lipidic metabolism in arteriosclerosis patients. Its use, in both the pre- and post-operative phases, has brought out the valuable effect of ligature of the intestinal lymphatics in treating arteritis. It may also enable us to determine whether there is a hereditary factor or family predisposition to arteriosclerosis. Furthermore, the test makes it possible to confirm diagnosis of obstruction of the lymphatics of the gut in exsudative enteropathy and in various dysfunctious of the chyliferous vessels (sclerosis, rupture, tumoral invasion) without to resort to the use of radioactive substances.", "contents": "[The induced hyperlipemia test. 10 years of experience]. The induced hyperlipemia test, which is easly to administer, yields very interesting information for the study of lipidic metabolism in arteriosclerosis patients. Its use, in both the pre- and post-operative phases, has brought out the valuable effect of ligature of the intestinal lymphatics in treating arteritis. It may also enable us to determine whether there is a hereditary factor or family predisposition to arteriosclerosis. Furthermore, the test makes it possible to confirm diagnosis of obstruction of the lymphatics of the gut in exsudative enteropathy and in various dysfunctious of the chyliferous vessels (sclerosis, rupture, tumoral invasion) without to resort to the use of radioactive substances."}
{"id": "PMID:216099", "title": "[Reversible humoral alterations paralleling the course of a recurring meningioma with metastases (author's transl)].", "content": "Case report of a recurring meningioma of the posterior fossa, with pulmonary metastases. Humoral alterations (sedimentation rate, fibrinemia, alkalin phosphatases, sideremia, prothrombin, blood proteins and BSP) paralleled the course of the tumor and may be considered as a para-tumoral syndrome. Pathogenesis is unknown.", "contents": "[Reversible humoral alterations paralleling the course of a recurring meningioma with metastases (author's transl)]. Case report of a recurring meningioma of the posterior fossa, with pulmonary metastases. Humoral alterations (sedimentation rate, fibrinemia, alkalin phosphatases, sideremia, prothrombin, blood proteins and BSP) paralleled the course of the tumor and may be considered as a para-tumoral syndrome. Pathogenesis is unknown."}
{"id": "PMID:216101", "title": "[A treatment of mild and moderate hypertension with timolol (author's transl)].", "content": "21 patients with essential sustained mild or moderate hypertension were treated with timolol for an average of 6 months at a mean dosage of 3,14 tablets per day. The mean decreases of supine systolic and diastolic blood pressures were respectively of 17,8 and 7,3 mm Hg. The efficacy of timolol was considered excellent or good in 11 cases (52,4 p. cent) and its tolerance perfect in 15 cases (71,4 p. cent). The study was extended in 15 cases with one dose of timolol per day. Effectiveness remained excellent in 12 cases. There was neither orthostatic hypotension nor brady-cardia of less than 55 beats per minute nor water retention. Side effects appeared in 6 cases requiring discontinance of therapy in only one case (exertional dyspnea).", "contents": "[A treatment of mild and moderate hypertension with timolol (author's transl)]. 21 patients with essential sustained mild or moderate hypertension were treated with timolol for an average of 6 months at a mean dosage of 3,14 tablets per day. The mean decreases of supine systolic and diastolic blood pressures were respectively of 17,8 and 7,3 mm Hg. The efficacy of timolol was considered excellent or good in 11 cases (52,4 p. cent) and its tolerance perfect in 15 cases (71,4 p. cent). The study was extended in 15 cases with one dose of timolol per day. Effectiveness remained excellent in 12 cases. There was neither orthostatic hypotension nor brady-cardia of less than 55 beats per minute nor water retention. Side effects appeared in 6 cases requiring discontinance of therapy in only one case (exertional dyspnea)."}
{"id": "PMID:216103", "title": "[Memorization and headaches (author's transl)].", "content": "The pathogenicity of headaches is still, in many cases, a mystery evoking the involvement or modification of basic algogenic processes. These types of headaches are usually resistant to true analgesics, and a medication which acts on the mesolimbic system could be effective. Tiapride, which has the characteristic of acting at this level, is not a true analgesic according to classical tests. Experimentally, however, it has been shown to inhibit the hypertensive algogenic response, which is a test of the overall response of the organism to painful stimuli. This special activity of tiapride probably accounts for its efficacy in many types of headache which are resistant to classical medication, the underlying tension, and emotional and memorization problems being due to the involvement of the mesolimbic system.", "contents": "[Memorization and headaches (author's transl)]. The pathogenicity of headaches is still, in many cases, a mystery evoking the involvement or modification of basic algogenic processes. These types of headaches are usually resistant to true analgesics, and a medication which acts on the mesolimbic system could be effective. Tiapride, which has the characteristic of acting at this level, is not a true analgesic according to classical tests. Experimentally, however, it has been shown to inhibit the hypertensive algogenic response, which is a test of the overall response of the organism to painful stimuli. This special activity of tiapride probably accounts for its efficacy in many types of headache which are resistant to classical medication, the underlying tension, and emotional and memorization problems being due to the involvement of the mesolimbic system."}
{"id": "PMID:216102", "title": "[Growth retardation in histiocytosis X. Evaluation of anterior pituitary function (author's transl)].", "content": "Among six patients with histiocytosis X of long duration and growth retardation of 3 to 4 standard deviations, three had a blunted growth hormone response to stimulation tests, associated to diabetes insipidus. In two of these three children there was a partial catchup of growth without treatment by human growth hormone. The causes and mechanisms of growth retardation in histiocytosis X, the influence of hydroelectrolytic disorders on growth in these patients and their need for treatment with human growth hormone are discussed.", "contents": "[Growth retardation in histiocytosis X. Evaluation of anterior pituitary function (author's transl)]. Among six patients with histiocytosis X of long duration and growth retardation of 3 to 4 standard deviations, three had a blunted growth hormone response to stimulation tests, associated to diabetes insipidus. In two of these three children there was a partial catchup of growth without treatment by human growth hormone. The causes and mechanisms of growth retardation in histiocytosis X, the influence of hydroelectrolytic disorders on growth in these patients and their need for treatment with human growth hormone are discussed."}
{"id": "PMID:216104", "title": "[Pharmacokinetics use in anti-cancer therapy (author's transl)].", "content": "Dynamic studies of anti-neoplasic agents provide a mathematical expression of various biological steps. High specific technics of dosage make possible the measurements of the drugs and their metabolites. Pharmacokinetics provides a new approach to three fundamental aspects in oncology: drug toxicity, relationship between drug schedule and response in each individual, drug resistance to anticancer drugs. Rational therapeutic approaches are made possible, as it was shown by the use of high dose of methotrexate.", "contents": "[Pharmacokinetics use in anti-cancer therapy (author's transl)]. Dynamic studies of anti-neoplasic agents provide a mathematical expression of various biological steps. High specific technics of dosage make possible the measurements of the drugs and their metabolites. Pharmacokinetics provides a new approach to three fundamental aspects in oncology: drug toxicity, relationship between drug schedule and response in each individual, drug resistance to anticancer drugs. Rational therapeutic approaches are made possible, as it was shown by the use of high dose of methotrexate."}
{"id": "PMID:216106", "title": "[The pulmonary aspiration-washing: new treatment of severe bacterial pneumopathies (author's transl)].", "content": "Over the last few years, the apparition of severe broncho-pulmonary suppurations in relation with an often poly-immune bacterial flora presents intricate therapeutic problems. The use of broncho-fibroscopy to enable several focussed cycles of broncho-pulmonary aspiration-washing perfusion, gave us interesting results.", "contents": "[The pulmonary aspiration-washing: new treatment of severe bacterial pneumopathies (author's transl)]. Over the last few years, the apparition of severe broncho-pulmonary suppurations in relation with an often poly-immune bacterial flora presents intricate therapeutic problems. The use of broncho-fibroscopy to enable several focussed cycles of broncho-pulmonary aspiration-washing perfusion, gave us interesting results."}
{"id": "PMID:216105", "title": "[A new therapeutical approach in neurology (author's transl)].", "content": "The therapeutic action of Tiapridal appeared to the authors particularly precious and constant in delirium tremens, senile agitation and turbulence, whatever the origin, and bucco-linguo-facial dyskinesia, whether the latter were linked to age or whether they formed part of a neuroleptic syndrome. Their experience does not permit them to have any opinion concerning the use of this drug in tremor and chorea, the patients seem to respond favourably to treatment but in an erratic manner. On the other hand the drug was totally inefficacious in patients suffering from spasmodic torticollis and writer's cramp. Finally, it seemed to them useful to emphasise the improvement in comfort in patients suffering from various pains when given Tiapridal. This justifies the place given to Tiapridal among drugs necessary for the daily practice of neurology.", "contents": "[A new therapeutical approach in neurology (author's transl)]. The therapeutic action of Tiapridal appeared to the authors particularly precious and constant in delirium tremens, senile agitation and turbulence, whatever the origin, and bucco-linguo-facial dyskinesia, whether the latter were linked to age or whether they formed part of a neuroleptic syndrome. Their experience does not permit them to have any opinion concerning the use of this drug in tremor and chorea, the patients seem to respond favourably to treatment but in an erratic manner. On the other hand the drug was totally inefficacious in patients suffering from spasmodic torticollis and writer's cramp. Finally, it seemed to them useful to emphasise the improvement in comfort in patients suffering from various pains when given Tiapridal. This justifies the place given to Tiapridal among drugs necessary for the daily practice of neurology."}
{"id": "PMID:216108", "title": "[Alpha chain disease. Report of a case (author's transl)].", "content": "A young patient, with alpha chain disease, is in good clinic condition, a little more than 4 years after the diagnosis. She received, during 1 year, antibiotics of tetracycline type, then antimitotics during 2 years. 9 months after antimitotics treatment was achieved, histologic signs remained unmodified, without evidence of degenerescence. Immunoelectrophoresis which was normal at the end of chemotherapy is always normal after 15 months without treatment.", "contents": "[Alpha chain disease. Report of a case (author's transl)]. A young patient, with alpha chain disease, is in good clinic condition, a little more than 4 years after the diagnosis. She received, during 1 year, antibiotics of tetracycline type, then antimitotics during 2 years. 9 months after antimitotics treatment was achieved, histologic signs remained unmodified, without evidence of degenerescence. Immunoelectrophoresis which was normal at the end of chemotherapy is always normal after 15 months without treatment."}
{"id": "PMID:216109", "title": "[Hemangioendothelioma of bone:  A propos of an anatamo-clinical observation].", "content": "Malignant hemangioendothelioma, localised to the skeleton of the lower limbs, to the exclusion of any other bony or visceral involvement, complicated by hemolytic anemia and spontaneous fractures, edl to death in spite of bilateral amputation, less than one year after its chance discovery. The multifocal character of the bony lesions, which is common, may suggest either rapidly developing metastases, or multicentric development of the tumour. The clinical, radiological and laboratory signs--pure osteolysis of large size without condensation nor periostosis, are not specific. Pathological examination permits recognition of the vascular origin of the tumour but does not always permit one to recognize its malignant nature. Treatment, which is mainly surgical, is often ineffective.", "contents": "[Hemangioendothelioma of bone:  A propos of an anatamo-clinical observation]. Malignant hemangioendothelioma, localised to the skeleton of the lower limbs, to the exclusion of any other bony or visceral involvement, complicated by hemolytic anemia and spontaneous fractures, edl to death in spite of bilateral amputation, less than one year after its chance discovery. The multifocal character of the bony lesions, which is common, may suggest either rapidly developing metastases, or multicentric development of the tumour. The clinical, radiological and laboratory signs--pure osteolysis of large size without condensation nor periostosis, are not specific. Pathological examination permits recognition of the vascular origin of the tumour but does not always permit one to recognize its malignant nature. Treatment, which is mainly surgical, is often ineffective."}
{"id": "PMID:216110", "title": "[Constrictive pericarditis and post-radiotherapy myocarditis with mitral incompetence (author's transl)].", "content": "The cardiac complications of radiotherapy of the thorax (e.g. for Hodgkin's disease and carcinoma of the breast) are various: 1) Pleural effusions, occurring a few months to two years after radiotherapy, spontaneously curable but may give signs of tamponnade or lead to constriction. 2) Constrictive pericarditis often several years after irradiation, with a poor prognosis in spite of attempts at pericardectomy which is indicated at the stage of hemodynamic constriction. 3) Myocardial involvement with advanced fibrosis and with various clinical presentations. The failure of pericardectomy and mitral incompetence were evidence of myocarditis in the case reported here.", "contents": "[Constrictive pericarditis and post-radiotherapy myocarditis with mitral incompetence (author's transl)]. The cardiac complications of radiotherapy of the thorax (e.g. for Hodgkin's disease and carcinoma of the breast) are various: 1) Pleural effusions, occurring a few months to two years after radiotherapy, spontaneously curable but may give signs of tamponnade or lead to constriction. 2) Constrictive pericarditis often several years after irradiation, with a poor prognosis in spite of attempts at pericardectomy which is indicated at the stage of hemodynamic constriction. 3) Myocardial involvement with advanced fibrosis and with various clinical presentations. The failure of pericardectomy and mitral incompetence were evidence of myocarditis in the case reported here."}
{"id": "PMID:216112", "title": "[Therapeutical test of Euthyral in thirty one cases of hypothyroidism (author's transl)].", "content": "Euthyral was prescribed in 31 cases of hypothyroidism. Plasma levels of T3, T4 and TSH were measured. Plasma TSH returned to normal values in all cases when daily doses of Euthyral exceeded 3/4 of a tablet. Plasma T4 returned to normal values in all cases when daily doses of Euthyral exceeded 3/4 of a tablet. Plasma T4 returned to normal values in all cases when daily doses of Euthyral exceeded half a tablet. Plasma T3 returned to normal values in all cases but was above normal values in 30 per cent of the cases when the daily doses of Euthyral exceeded 3/4 of a tablet.", "contents": "[Therapeutical test of Euthyral in thirty one cases of hypothyroidism (author's transl)]. Euthyral was prescribed in 31 cases of hypothyroidism. Plasma levels of T3, T4 and TSH were measured. Plasma TSH returned to normal values in all cases when daily doses of Euthyral exceeded 3/4 of a tablet. Plasma T4 returned to normal values in all cases when daily doses of Euthyral exceeded 3/4 of a tablet. Plasma T4 returned to normal values in all cases when daily doses of Euthyral exceeded half a tablet. Plasma T3 returned to normal values in all cases but was above normal values in 30 per cent of the cases when the daily doses of Euthyral exceeded 3/4 of a tablet."}
{"id": "PMID:216113", "title": "[The controversy concerning whooping cough vaccination (author's transl)].", "content": "The importance of the neurological complications of whooping cough vaccination has been greatly exaggerated. Their frequency may vary tenfold, depending on the authors. Most of the latter are mainly linked to age and are thus coincidences. Other etiologies may be responsible, as also may a receptive constitutional background, the vaccine then simply reveals a preexisting condition. Present whooping cough vaccines are efficacious as shown by the fall in morbidity curves and the large number of cases in unvaccinated subjects during epidemics. Whooping cough in infants remains a problem which can only be solved by vaccination. Primary vaccination should be carried out as early as possible, while strictly observing the contraindications. The poor absorption of whooping cough vaccines is in favour of their injection by the intramuscular route which is better tolerated. Other vaccines with less reaction and more immunogenic are being sought.", "contents": "[The controversy concerning whooping cough vaccination (author's transl)]. The importance of the neurological complications of whooping cough vaccination has been greatly exaggerated. Their frequency may vary tenfold, depending on the authors. Most of the latter are mainly linked to age and are thus coincidences. Other etiologies may be responsible, as also may a receptive constitutional background, the vaccine then simply reveals a preexisting condition. Present whooping cough vaccines are efficacious as shown by the fall in morbidity curves and the large number of cases in unvaccinated subjects during epidemics. Whooping cough in infants remains a problem which can only be solved by vaccination. Primary vaccination should be carried out as early as possible, while strictly observing the contraindications. The poor absorption of whooping cough vaccines is in favour of their injection by the intramuscular route which is better tolerated. Other vaccines with less reaction and more immunogenic are being sought."}
{"id": "PMID:216126", "title": "Hepatoblastoma. A case report.", "content": "A case of hepatoblastoma in a 16-month-old Black child is described and the classification of hepatoblastoma is reviewed. Early diagnosis is important, since the prognosis is more favourable in hepatoblastoma than in hepatocellular carcinoma.", "contents": "Hepatoblastoma. A case report. A case of hepatoblastoma in a 16-month-old Black child is described and the classification of hepatoblastoma is reviewed. Early diagnosis is important, since the prognosis is more favourable in hepatoblastoma than in hepatocellular carcinoma."}
{"id": "PMID:216127", "title": "Computed axial tomography in intracranial neoplasms in children.", "content": "The computed axial tomographic (CAT) findings in 22 children with intracranial neoplasms are presented. CAT offers a rapid, non-invasive method of assessing the locality and extent of these tumours, as well as the presence of calcification and hydrocephalus. CAT is of value in the follow-up treatment, but an absolute histological diagnosis is not always possible.", "contents": "Computed axial tomography in intracranial neoplasms in children. The computed axial tomographic (CAT) findings in 22 children with intracranial neoplasms are presented. CAT offers a rapid, non-invasive method of assessing the locality and extent of these tumours, as well as the presence of calcification and hydrocephalus. CAT is of value in the follow-up treatment, but an absolute histological diagnosis is not always possible."}
{"id": "PMID:216130", "title": "Cyclic nucleotides in platelet function.", "content": "Inhibition of adenylate cyclase in intact platelets by addition of compounds such as 2', 5' - dideoxyadenosine prevented the inhibition of platelet aggregation by PGE1 but did not affect the responses of platelets to aggregating agents in the absence of PGE1. This confirms that cyclic AMP mediates the effects of PGE1 but indicates that the level of cyclic AMP in unstimulated platelets is too low to affect the actions of aggregating agents. Studies on the phosphorylation of proteins in intact 32P-labelled platelets showed that PGE1 increased the phosphorylation of a membrane-bound polypeptide (P24) and prevented the increased phosphorylation of other polypeptides (P47 and P20) that occurred on addition of inducers of the release reaction. It is suggested that the cyclic AMP-dependent phosphorylation of P24 stimulates the active transport of Ca(2+) out of the platelet cytosol, so preventing phosphorylation of P47 and P20, reactions which may be involved in the release mechanism. As increases in platelet cyclic GMP could be dissociated from both platelet aggregation and the release reaction, it is proposed that the bidirectional regulation of platelet function is achieved primarily by the opposing actions of increases in the concentrations of Ca(2+) and cyclic AMP.", "contents": "Cyclic nucleotides in platelet function. Inhibition of adenylate cyclase in intact platelets by addition of compounds such as 2', 5' - dideoxyadenosine prevented the inhibition of platelet aggregation by PGE1 but did not affect the responses of platelets to aggregating agents in the absence of PGE1. This confirms that cyclic AMP mediates the effects of PGE1 but indicates that the level of cyclic AMP in unstimulated platelets is too low to affect the actions of aggregating agents. Studies on the phosphorylation of proteins in intact 32P-labelled platelets showed that PGE1 increased the phosphorylation of a membrane-bound polypeptide (P24) and prevented the increased phosphorylation of other polypeptides (P47 and P20) that occurred on addition of inducers of the release reaction. It is suggested that the cyclic AMP-dependent phosphorylation of P24 stimulates the active transport of Ca(2+) out of the platelet cytosol, so preventing phosphorylation of P47 and P20, reactions which may be involved in the release mechanism. As increases in platelet cyclic GMP could be dissociated from both platelet aggregation and the release reaction, it is proposed that the bidirectional regulation of platelet function is achieved primarily by the opposing actions of increases in the concentrations of Ca(2+) and cyclic AMP."}
{"id": "PMID:216128", "title": "Lesions of the caruncle: a clinicohistopathologic study.", "content": "This study reports 112 caruncular lesions seen in the Eye Pathology Laboratory of the Wilmer Institute during a 52-year period (1923--1976). These uncommon lesions are analyzed with regard to their relative occurrence and their clinical and histologic features. Clinical grouping of these lesions is presented to help in the differential diagnosis of caruncular lesions. Nevi, papillomas, and sebaceous gland hyperplasia were the most commonly encountered lesions, accounting for 65% of the total.", "contents": "Lesions of the caruncle: a clinicohistopathologic study. This study reports 112 caruncular lesions seen in the Eye Pathology Laboratory of the Wilmer Institute during a 52-year period (1923--1976). These uncommon lesions are analyzed with regard to their relative occurrence and their clinical and histologic features. Clinical grouping of these lesions is presented to help in the differential diagnosis of caruncular lesions. Nevi, papillomas, and sebaceous gland hyperplasia were the most commonly encountered lesions, accounting for 65% of the total."}
{"id": "PMID:216133", "title": "Detection of antibody to a new antigen induced by Epstein-Barr virus in rheumatoid arthritis.", "content": "A new antigen which is different from Epstein-Barr virion antigen was detected in NC-37 cells infected with Epstein-Barr virus (EBV). A significant elevation of the titer of antibody to this new antigen was observed in the sera of the patients with rheumatoid arthritis (RA), but not in the sera of controls. From the standpoint of the etiologic role of EBV in RA, it is interesting that the antibody to the new antigen is not detected in the healthy persons in contrast to other viral antibodies. Therefore, it differs from any other viral antibodies so far reported.", "contents": "Detection of antibody to a new antigen induced by Epstein-Barr virus in rheumatoid arthritis. A new antigen which is different from Epstein-Barr virion antigen was detected in NC-37 cells infected with Epstein-Barr virus (EBV). A significant elevation of the titer of antibody to this new antigen was observed in the sera of the patients with rheumatoid arthritis (RA), but not in the sera of controls. From the standpoint of the etiologic role of EBV in RA, it is interesting that the antibody to the new antigen is not detected in the healthy persons in contrast to other viral antibodies. Therefore, it differs from any other viral antibodies so far reported."}
{"id": "PMID:216134", "title": "Prevention of tissue factor generation in mononuclear cells by agents known to increase intracellular cyclic AMP.", "content": "Agents known to increase intracellular levels of cyclic 3', 5'-adenosine monophosphate (cyclic AMP) were examined for their effect on tissue factor generation by mononuclear cells cultured with E. coli endotoxin. Aminophylline, an inhibitor of phosphodiesterase, and epinephrine, a beta-adrenergic agent, showed an inhibitory effect, and these effects were reversible. Moreover, dibutyryl cyclic AMP also exhibited the effect. Dibutyryl cyclic GMP, however, did not enhance the tissue factor generation by mononuclear cells. On the basis of these observations, it was concluded that the phenomenon of tissue factor generation by mononuclear cells is a biological event, and that intracellular cyclic AMP has a possible role in modulating this phenomenon.", "contents": "Prevention of tissue factor generation in mononuclear cells by agents known to increase intracellular cyclic AMP. Agents known to increase intracellular levels of cyclic 3', 5'-adenosine monophosphate (cyclic AMP) were examined for their effect on tissue factor generation by mononuclear cells cultured with E. coli endotoxin. Aminophylline, an inhibitor of phosphodiesterase, and epinephrine, a beta-adrenergic agent, showed an inhibitory effect, and these effects were reversible. Moreover, dibutyryl cyclic AMP also exhibited the effect. Dibutyryl cyclic GMP, however, did not enhance the tissue factor generation by mononuclear cells. On the basis of these observations, it was concluded that the phenomenon of tissue factor generation by mononuclear cells is a biological event, and that intracellular cyclic AMP has a possible role in modulating this phenomenon."}
{"id": "PMID:216135", "title": "Machakos Project Studies: agents affecting health of mother and child in a rural area of Kenya. VII. The incidence of diarrhoeal disease in the under-five population.", "content": "The outcome of three years of fortnightly diarrhoea surveillance of about 4000 children under the age of five is described. The two-weekly incidence of diarrhoea in children in the age group 0-5 months, 6-11 months and 12-23 months, who were reported and/or observed to be ill, was 3.4%, 5.6% and 3.4% respectively. A decline in the attack rates of diarrhoea not associated with measles at the end of 1975 and the beginning of 1976 corresponds with a similar decline in the incidence of measles and malnutrition. Initially diarrhoea information was only obtained from children who where reported and/or observed to be ill; later on, all mothers were questioned about their children's diarrhoea experience at the moment of the fieldworkers's visit or in the preceding two weeks. This yielded a four to sevenfold increase in diarrhoea incidence. Thus, diarrhoea appears to be a common condition among under-fives which is not necessarily considered to be an illness by the mother.", "contents": "Machakos Project Studies: agents affecting health of mother and child in a rural area of Kenya. VII. The incidence of diarrhoeal disease in the under-five population. The outcome of three years of fortnightly diarrhoea surveillance of about 4000 children under the age of five is described. The two-weekly incidence of diarrhoea in children in the age group 0-5 months, 6-11 months and 12-23 months, who were reported and/or observed to be ill, was 3.4%, 5.6% and 3.4% respectively. A decline in the attack rates of diarrhoea not associated with measles at the end of 1975 and the beginning of 1976 corresponds with a similar decline in the incidence of measles and malnutrition. Initially diarrhoea information was only obtained from children who where reported and/or observed to be ill; later on, all mothers were questioned about their children's diarrhoea experience at the moment of the fieldworkers's visit or in the preceding two weeks. This yielded a four to sevenfold increase in diarrhoea incidence. Thus, diarrhoea appears to be a common condition among under-fives which is not necessarily considered to be an illness by the mother."}
{"id": "PMID:216136", "title": "[Transformation of human embryonic cells by the Rous sarcoma virus and the polyomavirus depending on the mitotic cycle phase].", "content": "The whole cycle of skin-muscle embryonic human tissue culture is 18 hours, with phases S, G1, G2 and M being 7, 6, 4 and 1 hour, respectively. The mitotic index of this culture is 28%. The maximum sensitivity of these synchronized cell cultures to transforming activity of the Rous and Sindai viruses was observed in phase S. The infection of synchronized primary embryonic human fibroblasts in phase S with the polyoma virus together with the Sindai virus has resulted in single cases of transformation. Similar results were obtained with non-synchronized human cultures.", "contents": "[Transformation of human embryonic cells by the Rous sarcoma virus and the polyomavirus depending on the mitotic cycle phase]. The whole cycle of skin-muscle embryonic human tissue culture is 18 hours, with phases S, G1, G2 and M being 7, 6, 4 and 1 hour, respectively. The mitotic index of this culture is 28%. The maximum sensitivity of these synchronized cell cultures to transforming activity of the Rous and Sindai viruses was observed in phase S. The infection of synchronized primary embryonic human fibroblasts in phase S with the polyoma virus together with the Sindai virus has resulted in single cases of transformation. Similar results were obtained with non-synchronized human cultures."}
{"id": "PMID:216139", "title": "Comparative electron-microscopic studies of benign hepatoma and icterus in patients on oral contraceptives.", "content": "The author compared the electron-microscopic picture of 6 benign hepatomas and 3 specimens of icteric liver tissue in female patients on oral contraceptives. The majority of ultrastructural changes seen were identical in the tumor and non-tumor cases. It is noteworthy that there is an accumulation of filamentous substance of unknown origin in the bile canaliculi and in the Disse's spaces associated with a damage to the cell membrane. The electron-microscopic picture of the sinusoidal endothelial cells suggested an increased protein producing activity. The most conspicuous feature of the tumours was formation of continuous capillaries at the site of the sinusoids. The importance of systematic electron-microscopic investigation in studying the effect of oral contraceptives on the liver cells is stressed by the author.", "contents": "Comparative electron-microscopic studies of benign hepatoma and icterus in patients on oral contraceptives. The author compared the electron-microscopic picture of 6 benign hepatomas and 3 specimens of icteric liver tissue in female patients on oral contraceptives. The majority of ultrastructural changes seen were identical in the tumor and non-tumor cases. It is noteworthy that there is an accumulation of filamentous substance of unknown origin in the bile canaliculi and in the Disse's spaces associated with a damage to the cell membrane. The electron-microscopic picture of the sinusoidal endothelial cells suggested an increased protein producing activity. The most conspicuous feature of the tumours was formation of continuous capillaries at the site of the sinusoids. The importance of systematic electron-microscopic investigation in studying the effect of oral contraceptives on the liver cells is stressed by the author."}
{"id": "PMID:216142", "title": "[Cyclic 3',5'-AMP metabolism in progressive muscular dystrophy patients].", "content": "Concentration of cyclic AMP was distinctly decreased in muscular tissue of patients with Dushenn's myodystrophy. Simultaneously, in patients with the myopathy basal activity of adenylate cyclase as well as activation of the enzyme by adrenaline and sodium fluoride were decreased. As a compensation, activity of phosphodiesterase was also decreased. Content of cAMP, activity and activation of adenylate cyclase were similar to normal state in patients with Erb's and Landuzi--Dejerin's myopathies; activity of phosphodiesterase was increased in the latter impairment. Dissociation constant for binding of cAMP by protein kinases was more than 10-fold decreased in patients with these types of myopathy.", "contents": "[Cyclic 3',5'-AMP metabolism in progressive muscular dystrophy patients]. Concentration of cyclic AMP was distinctly decreased in muscular tissue of patients with Dushenn's myodystrophy. Simultaneously, in patients with the myopathy basal activity of adenylate cyclase as well as activation of the enzyme by adrenaline and sodium fluoride were decreased. As a compensation, activity of phosphodiesterase was also decreased. Content of cAMP, activity and activation of adenylate cyclase were similar to normal state in patients with Erb's and Landuzi--Dejerin's myopathies; activity of phosphodiesterase was increased in the latter impairment. Dissociation constant for binding of cAMP by protein kinases was more than 10-fold decreased in patients with these types of myopathy."}
{"id": "PMID:216147", "title": "[Changes in the lung tissue in bronchial adenomas].", "content": "Changes in the lung tissue in bronchial adenomas are not dependent on their histological structure, but on the anatomical form of growth, localization and duration of the existance. Both peripheral adenomas and cancer may have an asymptomatic course. In central (especially exophitic) adenomas distelectasis, atelectasis, fibrosis and vascular regeneration develop in sequence, while with the secondary infection-pneumonic foci. In relation to the mechanism of the development, lung tissue changes may arise as a result of invasive tumor growth, hypoxia, and impaired drainage function of the bronchi, toxico-immunological disturbances.", "contents": "[Changes in the lung tissue in bronchial adenomas]. Changes in the lung tissue in bronchial adenomas are not dependent on their histological structure, but on the anatomical form of growth, localization and duration of the existance. Both peripheral adenomas and cancer may have an asymptomatic course. In central (especially exophitic) adenomas distelectasis, atelectasis, fibrosis and vascular regeneration develop in sequence, while with the secondary infection-pneumonic foci. In relation to the mechanism of the development, lung tissue changes may arise as a result of invasive tumor growth, hypoxia, and impaired drainage function of the bronchi, toxico-immunological disturbances."}
{"id": "PMID:216141", "title": "[Functioning of rat liver mitochondria in hepatitis].", "content": "Parameters of oxidative phosphorylation, the rate of respiration in various metabolic conditions as well as an activity and stability of mitochondrial polyenzyme systems were altered in rats with experimental hepatitis, treated with CCl4. Proteins and phospholipids from mitochondrial membranes proved to be more susceptible to the effect of trypsin and phospholipase D. Kinetics of cytochrome C desorption from membranes and mitochondria demonstrated that capacity of these membranes to confine the exogenous proteins was altered in hepatitis.", "contents": "[Functioning of rat liver mitochondria in hepatitis]. Parameters of oxidative phosphorylation, the rate of respiration in various metabolic conditions as well as an activity and stability of mitochondrial polyenzyme systems were altered in rats with experimental hepatitis, treated with CCl4. Proteins and phospholipids from mitochondrial membranes proved to be more susceptible to the effect of trypsin and phospholipase D. Kinetics of cytochrome C desorption from membranes and mitochondria demonstrated that capacity of these membranes to confine the exogenous proteins was altered in hepatitis."}
{"id": "PMID:216143", "title": "[Cyclic AMP system in muscle tissue during prolonged hypokinesia].", "content": "Constituents of cAMP system were studied in prolonged hypokinesia (70--75 days) and within the period of readaptation of muscular tissue in rats. Content of cAMP as well as activities of adenylate cyclase and phosphodiesterase were increased in muscles at the initial period of limited mobility (especially, within the first 5 days). Within the period of so-called \"adaptation\" (during the first 24--37 days) content of cAMP and activity of both enzymes were practically similar to control values. Distinct decrease in cAMP content, activation of phosphodiesterase and decrease in stimulating effect of adrenaline on adenylate cyclase activity were observed within the first 70 days of the experiment. Pronounced normalization of the patterns studied occurred within the period of readaptation.", "contents": "[Cyclic AMP system in muscle tissue during prolonged hypokinesia]. Constituents of cAMP system were studied in prolonged hypokinesia (70--75 days) and within the period of readaptation of muscular tissue in rats. Content of cAMP as well as activities of adenylate cyclase and phosphodiesterase were increased in muscles at the initial period of limited mobility (especially, within the first 5 days). Within the period of so-called \"adaptation\" (during the first 24--37 days) content of cAMP and activity of both enzymes were practically similar to control values. Distinct decrease in cAMP content, activation of phosphodiesterase and decrease in stimulating effect of adrenaline on adenylate cyclase activity were observed within the first 70 days of the experiment. Pronounced normalization of the patterns studied occurred within the period of readaptation."}
{"id": "PMID:216145", "title": "[Hypolipidemic activity of substances structurally close to penphenone in rats and mice].", "content": "Effect of substances, structurally related to penphenone (2-phenyl-3-methyl-3-hydroxypentanic acid sodium salt), was studied on the main patterns of lipid metabolism in blood of rats and mice, as well as on lipoprotein spectra of rat blood serum. All the compounds studied exhibited hypolipidemic effect, decreasing concentration of total cholesterol, cholesterol of alpha-lipoproteins and triglycerides in rat blood. The effect was less distinct in mice. 2-phenyl-3,4-dimethyl-3-hydroxypentanic acid sodium salt possessed the most pronounced hypolipidemic effect. A decrease in content of beta-and pre-beta-lipoproteins as well as of alpha-lipoproteins was observed after electrophoretic separation of blood serum lipoproteins in polyacrylamide gel in animals treated with the compound.", "contents": "[Hypolipidemic activity of substances structurally close to penphenone in rats and mice]. Effect of substances, structurally related to penphenone (2-phenyl-3-methyl-3-hydroxypentanic acid sodium salt), was studied on the main patterns of lipid metabolism in blood of rats and mice, as well as on lipoprotein spectra of rat blood serum. All the compounds studied exhibited hypolipidemic effect, decreasing concentration of total cholesterol, cholesterol of alpha-lipoproteins and triglycerides in rat blood. The effect was less distinct in mice. 2-phenyl-3,4-dimethyl-3-hydroxypentanic acid sodium salt possessed the most pronounced hypolipidemic effect. A decrease in content of beta-and pre-beta-lipoproteins as well as of alpha-lipoproteins was observed after electrophoretic separation of blood serum lipoproteins in polyacrylamide gel in animals treated with the compound."}
{"id": "PMID:216149", "title": "[Antibody formation in type A viral hepatitis].", "content": "Immune response to hepatitis type A antigen (HAAg) was measured by the passive hemagglutination test (PHA) and by the immune adherence test (IAHA). Specific antibodies found by PHA are of the IgM class which indicates a recent exposure to hepatitis A virus. The antibodies found by IAHA reflect the level of postinfectious immune status. The antibody curve is highest in the age group of 30--49 years (95%). The above-mentioned serological tests were carried out with purified by gel filtration in Sepharose 6B Botevgrad faecal morphologically consisting of 27 nm particles with the buoyant density in CcCl of 1.40 g/ml. The same particles were aggregated with sera positive for antibody to hepatitis type A antigen in immune electron microscopy (IEM).", "contents": "[Antibody formation in type A viral hepatitis]. Immune response to hepatitis type A antigen (HAAg) was measured by the passive hemagglutination test (PHA) and by the immune adherence test (IAHA). Specific antibodies found by PHA are of the IgM class which indicates a recent exposure to hepatitis A virus. The antibodies found by IAHA reflect the level of postinfectious immune status. The antibody curve is highest in the age group of 30--49 years (95%). The above-mentioned serological tests were carried out with purified by gel filtration in Sepharose 6B Botevgrad faecal morphologically consisting of 27 nm particles with the buoyant density in CcCl of 1.40 g/ml. The same particles were aggregated with sera positive for antibody to hepatitis type A antigen in immune electron microscopy (IEM)."}
{"id": "PMID:216151", "title": "[Detection of an agent similar to rotavirus in infantile gastroenteritis].", "content": "The etiology of nonbacterial enterovirus infections in children was studied in autumn and winter under conditions of focal outbreaks in Moscow hospitals. Electron microscopy revealed a reovirus-like agent in concentrated suspensions of feces collected in the acute period of the disease from children suffering from diarrhea. Examinations of paired sera from the patients by the CF test with the antigen of Nebraska calf disease virus established significant rises in antibody titers in 68.3% of cases. The results permit a conclusion that in this country a virus of acute gastroenteritis of children (viral gastroenteritis A) is circulating, causing outbreaks of the disease. The virus belongs to the genus Rotavirus of the Reoviridae family.", "contents": "[Detection of an agent similar to rotavirus in infantile gastroenteritis]. The etiology of nonbacterial enterovirus infections in children was studied in autumn and winter under conditions of focal outbreaks in Moscow hospitals. Electron microscopy revealed a reovirus-like agent in concentrated suspensions of feces collected in the acute period of the disease from children suffering from diarrhea. Examinations of paired sera from the patients by the CF test with the antigen of Nebraska calf disease virus established significant rises in antibody titers in 68.3% of cases. The results permit a conclusion that in this country a virus of acute gastroenteritis of children (viral gastroenteritis A) is circulating, causing outbreaks of the disease. The virus belongs to the genus Rotavirus of the Reoviridae family."}
{"id": "PMID:216153", "title": "[Activity of lactate dehydrogenase and its isofractions in experimental asymptomatic adenovirus infections].", "content": "Experimentally in 147 dog puppies an asymptomatic infection caused by adenovirus of human origin was produced and the process was caused to become manifest by administration of the same virus against the background of the effect of antilymphocyte serum. The activity of LDG in asymptomatic adenovirus infection was found to decrease in the cytoplasmic fraction of hepatocytes and to increase in the blood serum. An increase in the content of the \"hepatic\" complex of LDG in the blood serum and its decrease in the cytoplasmic fraction of hepatocytes was established indicating disorders in the liver function. It is concluded that asymptomatic adenovirus infection leads to the formation of the state of pre-pathology. Manifestation of the infection enhances the quantitative aspect of the changes.", "contents": "[Activity of lactate dehydrogenase and its isofractions in experimental asymptomatic adenovirus infections]. Experimentally in 147 dog puppies an asymptomatic infection caused by adenovirus of human origin was produced and the process was caused to become manifest by administration of the same virus against the background of the effect of antilymphocyte serum. The activity of LDG in asymptomatic adenovirus infection was found to decrease in the cytoplasmic fraction of hepatocytes and to increase in the blood serum. An increase in the content of the \"hepatic\" complex of LDG in the blood serum and its decrease in the cytoplasmic fraction of hepatocytes was established indicating disorders in the liver function. It is concluded that asymptomatic adenovirus infection leads to the formation of the state of pre-pathology. Manifestation of the infection enhances the quantitative aspect of the changes."}
{"id": "PMID:216152", "title": "[Several characteristics of new strains of diploid green marmoset fibroblasts].", "content": "Two strains of diploid fibroblasts were derived from green monkey fetal lungs and their main properties were studied. These strains were shown not to differ principally from the well studied human diploid fibroblasts. The derived cultures are free from contaminating viruses. The titers of attenuated poliomyelitis virus strains achieved in green monkey diploid cells are comparable to those in primary cultures of green monkey kidneys. The possiblity of using green monkey diploid fibroblasts in virological practice is discussed.", "contents": "[Several characteristics of new strains of diploid green marmoset fibroblasts]. Two strains of diploid fibroblasts were derived from green monkey fetal lungs and their main properties were studied. These strains were shown not to differ principally from the well studied human diploid fibroblasts. The derived cultures are free from contaminating viruses. The titers of attenuated poliomyelitis virus strains achieved in green monkey diploid cells are comparable to those in primary cultures of green monkey kidneys. The possiblity of using green monkey diploid fibroblasts in virological practice is discussed."}
{"id": "PMID:216155", "title": "[Development of a method of concentrating enteroviruses for virologic studies of meat].", "content": "A method for concentration of enteroviruses in meat extracts was developed using polyvinylpyrrolidone (molecular mass 10,000), polyethylene glycol (molecular mass 15,000), both in 10% concentration, silicagel with a granule size of 200 mesh in a concentration of 5%, aluminum hydroxide in an amount of centrifuged pellet of 5 ml of original suspension per 10 ml meat extract. When the optimal conditions of meat extract preparation (meat mass: Hanks' solution ration 1: 10) were observed, followed by virus concentration in polymers of silicagel 2--4 PFU of enteroviruses in 1 g of meat could be determined in all the experiments. Virus doses of 0.2--0.5 PFU per 1 g of meat could be detected in some experiments.", "contents": "[Development of a method of concentrating enteroviruses for virologic studies of meat]. A method for concentration of enteroviruses in meat extracts was developed using polyvinylpyrrolidone (molecular mass 10,000), polyethylene glycol (molecular mass 15,000), both in 10% concentration, silicagel with a granule size of 200 mesh in a concentration of 5%, aluminum hydroxide in an amount of centrifuged pellet of 5 ml of original suspension per 10 ml meat extract. When the optimal conditions of meat extract preparation (meat mass: Hanks' solution ration 1: 10) were observed, followed by virus concentration in polymers of silicagel 2--4 PFU of enteroviruses in 1 g of meat could be determined in all the experiments. Virus doses of 0.2--0.5 PFU per 1 g of meat could be detected in some experiments."}
{"id": "PMID:216154", "title": "[Isolation of type 71 enterovirus from patients with a poliomyelitis-like disease during an outbreak in Bulgaria].", "content": "Virological examinations of 72 specimens obtained during an outbreak of a poliomyelitis-like disease in Bulgaria, 1975, yielded 23 strains of enterovirus type 71 (E71) and 5 strains of enteroviruses of other types. The viruses were isolated in green monkey kidney cell cultures, in newborn cotton rats, newborn white mice and in monkeys. Most of E71 strains (16 out of 23) were isolated from the autopsy materials (brains and spinal cords) from 9 children dying of poliomyelitis, meningoencephalitis, and encephalitis. The remaining E71 strains and all the strains of other enterovirus serotypes, with the exception of ECHO7, were isolated from stool specimens of children with aseptic meningitis and their contacts. The antigenic similarity of the group of Bulgarian strains and their relationship with the prototype BrCr strain of E71 was established. The conclusion is that E71 was the causative agent of an outbreak of a poliomyelitis-like disease in Bulgaria.", "contents": "[Isolation of type 71 enterovirus from patients with a poliomyelitis-like disease during an outbreak in Bulgaria]. Virological examinations of 72 specimens obtained during an outbreak of a poliomyelitis-like disease in Bulgaria, 1975, yielded 23 strains of enterovirus type 71 (E71) and 5 strains of enteroviruses of other types. The viruses were isolated in green monkey kidney cell cultures, in newborn cotton rats, newborn white mice and in monkeys. Most of E71 strains (16 out of 23) were isolated from the autopsy materials (brains and spinal cords) from 9 children dying of poliomyelitis, meningoencephalitis, and encephalitis. The remaining E71 strains and all the strains of other enterovirus serotypes, with the exception of ECHO7, were isolated from stool specimens of children with aseptic meningitis and their contacts. The antigenic similarity of the group of Bulgarian strains and their relationship with the prototype BrCr strain of E71 was established. The conclusion is that E71 was the causative agent of an outbreak of a poliomyelitis-like disease in Bulgaria."}
{"id": "PMID:216167", "title": "[Steroid-examinations in serum of old men as a functional testing of the suprarenal glands (author's transl)].", "content": "A surgical intervention is dangerous for the old patient awing to the reduced reactiveness and polymorbity. The knowledge of the function of the suprarenal glands in stress (operation) is important. The latent insufficiency of the suprarenal glands is determined with the ACTH-stimulations test. 136 patients from 60 to 100 years were proved. In the case of a latent insufficiency of the suprarenal glands the substitution of glucocorticoids and ACTH is necessary.", "contents": "[Steroid-examinations in serum of old men as a functional testing of the suprarenal glands (author's transl)]. A surgical intervention is dangerous for the old patient awing to the reduced reactiveness and polymorbity. The knowledge of the function of the suprarenal glands in stress (operation) is important. The latent insufficiency of the suprarenal glands is determined with the ACTH-stimulations test. 136 patients from 60 to 100 years were proved. In the case of a latent insufficiency of the suprarenal glands the substitution of glucocorticoids and ACTH is necessary."}
{"id": "PMID:216163", "title": "Potassium adaptation after reduction of nephron population.", "content": "Two weeks after 75 percent nephrectomy in rats fed a normal diet glomerular filtration rate was found to be reduced by 2/3 and there was no hyperkalemia. Normal K balance was maintained by a threefold increase of fractional urinary potassium excretion. When infused with 0.5 M KCl solution, both normal and 75 percent nephrectomized rats increased their fractional excretion, while normal rats kept on a very high K-diet did not further increase their fractional potassium excretion. Adaptation of fractional excretion to infused KCl was blunted in 75 percent nephrectomized rats given a low K diet.Addition of 0.1 M KCl to the drinking water resulted in a three- to fourfold increase of potassium intake in normal rats: within 7 days, the Na-K-ATPase in the outer medulla of the kidney rose by 30 percent but no change occurred in the cortex. Further increases in dietary K load induced an increase of Na-K-ATPase activity, both in outer medulla and cortex, but not in other tissues. After 75 percent nephrectomy, specific Na-K-ATPase activity increased by 20-25 percent in the outer medulla and in the cortex.Dietary K loading, in normal rats, also resulted in a large increase of net potassium secretion into the perfused colon and of specific Na-K-ATPase activity of the colonic mucosa. These effects of potassium loading were not abolished by adrenalectomy and were accompanied by an increase of transmural PD. It was concluded that chronic potassium loading may enhance secretion of potassium into lower nephron tubular fluid and into colonic contents by primarily stimulating the synthesis of Na-K-ATPase and the resulting increase of the number of pumping sites. 75 percent nephrectomy may induce similar changes in the remaining nephrons.", "contents": "Potassium adaptation after reduction of nephron population. Two weeks after 75 percent nephrectomy in rats fed a normal diet glomerular filtration rate was found to be reduced by 2/3 and there was no hyperkalemia. Normal K balance was maintained by a threefold increase of fractional urinary potassium excretion. When infused with 0.5 M KCl solution, both normal and 75 percent nephrectomized rats increased their fractional excretion, while normal rats kept on a very high K-diet did not further increase their fractional potassium excretion. Adaptation of fractional excretion to infused KCl was blunted in 75 percent nephrectomized rats given a low K diet.Addition of 0.1 M KCl to the drinking water resulted in a three- to fourfold increase of potassium intake in normal rats: within 7 days, the Na-K-ATPase in the outer medulla of the kidney rose by 30 percent but no change occurred in the cortex. Further increases in dietary K load induced an increase of Na-K-ATPase activity, both in outer medulla and cortex, but not in other tissues. After 75 percent nephrectomy, specific Na-K-ATPase activity increased by 20-25 percent in the outer medulla and in the cortex.Dietary K loading, in normal rats, also resulted in a large increase of net potassium secretion into the perfused colon and of specific Na-K-ATPase activity of the colonic mucosa. These effects of potassium loading were not abolished by adrenalectomy and were accompanied by an increase of transmural PD. It was concluded that chronic potassium loading may enhance secretion of potassium into lower nephron tubular fluid and into colonic contents by primarily stimulating the synthesis of Na-K-ATPase and the resulting increase of the number of pumping sites. 75 percent nephrectomy may induce similar changes in the remaining nephrons."}
{"id": "PMID:216164", "title": "Factors influencing the increase in Na-K-ATPase in compensatory renal hypertrophy.", "content": "An increase in Na-K-ATPase in kidney homogenates usually accompanies compensatory renal hypertrophy. While it may be evident in both the cortex and medulla of the kidney, it is most marked in the outer medulla and may be present only in that region. The increase in enzyme activity does not depend on an intact adrenal cortex and can be elicited in the absence of adrenal glucocorticoids. It is not seen in the form of renal hypertrophy produced by potassium depletion, in which the transport of sodium and potassium by the kidney is not increased. When present in compensatory renal growth, the enzyme change is correlated with an increase in the reabsorption of sodium, or the excretion of potassium, or both, per unit of renal tissue. It proceeds in the presence of either, but not in the absence of both.", "contents": "Factors influencing the increase in Na-K-ATPase in compensatory renal hypertrophy. An increase in Na-K-ATPase in kidney homogenates usually accompanies compensatory renal hypertrophy. While it may be evident in both the cortex and medulla of the kidney, it is most marked in the outer medulla and may be present only in that region. The increase in enzyme activity does not depend on an intact adrenal cortex and can be elicited in the absence of adrenal glucocorticoids. It is not seen in the form of renal hypertrophy produced by potassium depletion, in which the transport of sodium and potassium by the kidney is not increased. When present in compensatory renal growth, the enzyme change is correlated with an increase in the reabsorption of sodium, or the excretion of potassium, or both, per unit of renal tissue. It proceeds in the presence of either, but not in the absence of both."}
{"id": "PMID:216165", "title": "Cyclic nucleotide concentrations in relation to renal growth and hypertrophy.", "content": "In rats no consistent change in the concentration of cyclic GMP or cyclic AMP concentration was found in the renal cortex between 2 hours and seven days after unilateral nephrectomy. In regenerating liver tissue, between 2 hours and seven days after removal of one-third of the liver, there were no consistent changes in cyclic GMP concentrations, but cyclic AMP concentrations were higher than in controls. During postnatal growth, no consistent changes occurred in the cyclic GMP concentration of the spleen, the testes, the kidney cortex, the renal papilla, the liver or the ventricle between two and sixty days after birth. Cyclic AMP concentration on the other hand, in all these tissues with the exception of the spleen, was depressed between the twenty-first and fortieth day after birth, i.e., at a period of rapid growth. In the spleen, the concentration of cyclic AMP increased continuously from the second to the fifth day after birth. During renal parenchymal hyperplasia induced by a large intravenous dose of folic acid two days before sacrifice, the concentration of cyclic GMP in renal cortical tissue increased consistently. A model is proposed to explain the different patterns of changes in the cyclic nucleotide concentrations found.", "contents": "Cyclic nucleotide concentrations in relation to renal growth and hypertrophy. In rats no consistent change in the concentration of cyclic GMP or cyclic AMP concentration was found in the renal cortex between 2 hours and seven days after unilateral nephrectomy. In regenerating liver tissue, between 2 hours and seven days after removal of one-third of the liver, there were no consistent changes in cyclic GMP concentrations, but cyclic AMP concentrations were higher than in controls. During postnatal growth, no consistent changes occurred in the cyclic GMP concentration of the spleen, the testes, the kidney cortex, the renal papilla, the liver or the ventricle between two and sixty days after birth. Cyclic AMP concentration on the other hand, in all these tissues with the exception of the spleen, was depressed between the twenty-first and fortieth day after birth, i.e., at a period of rapid growth. In the spleen, the concentration of cyclic AMP increased continuously from the second to the fifth day after birth. During renal parenchymal hyperplasia induced by a large intravenous dose of folic acid two days before sacrifice, the concentration of cyclic GMP in renal cortical tissue increased consistently. A model is proposed to explain the different patterns of changes in the cyclic nucleotide concentrations found."}
{"id": "PMID:216170", "title": "[The abdominal tuberculoses].", "content": "In a report on the extrapulmonary tuberculosis the abdominal forms are once more emphasized and analysed on the basis of a number of patients. There are no more any actual references to this picture of a disease in the modern general situation of tuberculosis, as by abolition of the bovine tuberculosis the prerequisites could be removed. There is no decisive symptomatology which leads to an abdominal tuberculosis. With the help of 89 clinically treated cases certain problems could be elaborated with regard to the diagnostics and therapy. The inclination to recidivation is not unconsiderable (8.9%), which is due to a disappointing bacteriological diagnostics and the false chemotherapeutic treatments resulting from this. With 34 cases in the GDR in 1976 this tuberculous disease is at present scarcely still of any significance. It must also in future be reckoned with sporadic new diseases which appear due to an intermittent lympho-haematogenic dissemination from tuberculous lung, pleura or lymph node processes and which may be treated with success by a modern multiple chemotherapy in a tuberculosis institution. The severe courses accompanied by complications which gave rise to surgical emergency measures might finally belong to the past.", "contents": "[The abdominal tuberculoses]. In a report on the extrapulmonary tuberculosis the abdominal forms are once more emphasized and analysed on the basis of a number of patients. There are no more any actual references to this picture of a disease in the modern general situation of tuberculosis, as by abolition of the bovine tuberculosis the prerequisites could be removed. There is no decisive symptomatology which leads to an abdominal tuberculosis. With the help of 89 clinically treated cases certain problems could be elaborated with regard to the diagnostics and therapy. The inclination to recidivation is not unconsiderable (8.9%), which is due to a disappointing bacteriological diagnostics and the false chemotherapeutic treatments resulting from this. With 34 cases in the GDR in 1976 this tuberculous disease is at present scarcely still of any significance. It must also in future be reckoned with sporadic new diseases which appear due to an intermittent lympho-haematogenic dissemination from tuberculous lung, pleura or lymph node processes and which may be treated with success by a modern multiple chemotherapy in a tuberculosis institution. The severe courses accompanied by complications which gave rise to surgical emergency measures might finally belong to the past."}
{"id": "PMID:216171", "title": "[Results of islet transplantation in diabetic dogs].", "content": "The influence of histocompatibility on islet transplantation in dogs was studied. Donors and hosts were chosen by help of the macrophage-electrophoresis-mobility test. By subtotal pancreatectomy and twice applying streptocotocin diabetes was successfully induced in recipient animals. Isolation of pancreating islets from the donor was done by means of the collagenase method combined with the Ficoll-gradient-separating technique. The grafting occurred via portal vein into the liver. Significant decrease of blood sugar during 10 weeks was observed in animals with good compatibility. This effect lasted only 14 days in cases of bad compatibility. Concentrations of insulin in the portal vein and superior caval vein 4 weeks after grafting was lower in cases with high-grade histoincompatibility. The duration of functioning of transplanted islets depends on the histocompatibility.", "contents": "[Results of islet transplantation in diabetic dogs]. The influence of histocompatibility on islet transplantation in dogs was studied. Donors and hosts were chosen by help of the macrophage-electrophoresis-mobility test. By subtotal pancreatectomy and twice applying streptocotocin diabetes was successfully induced in recipient animals. Isolation of pancreating islets from the donor was done by means of the collagenase method combined with the Ficoll-gradient-separating technique. The grafting occurred via portal vein into the liver. Significant decrease of blood sugar during 10 weeks was observed in animals with good compatibility. This effect lasted only 14 days in cases of bad compatibility. Concentrations of insulin in the portal vein and superior caval vein 4 weeks after grafting was lower in cases with high-grade histoincompatibility. The duration of functioning of transplanted islets depends on the histocompatibility."}
{"id": "PMID:216172", "title": "[Effect of Collins' solution the kidney concentrating gradient and the Na+ and K+-ATPase of the kidney].", "content": "Canine kidneys were preserved under hypothermia in Collins' standard solution and the contents of sodium, potassium, and Na+ and K+-ATPase in several parts of these kidneys were followed. Hypothermic preservation in combination with single perfusion by means of Collins' solution without thermic ischemia caused loss of sodium, increase of potassium, and decrease of the total osmotic cortico-papillary gradient of the kidney. No loss of Na+ and K+-ATPase activity occurred under these conditions. The determination of Na+ and K+-ATPase level in the renal tissue turns out to be a rational method to assess the vitality of an organ to be transplanted.", "contents": "[Effect of Collins' solution the kidney concentrating gradient and the Na+ and K+-ATPase of the kidney]. Canine kidneys were preserved under hypothermia in Collins' standard solution and the contents of sodium, potassium, and Na+ and K+-ATPase in several parts of these kidneys were followed. Hypothermic preservation in combination with single perfusion by means of Collins' solution without thermic ischemia caused loss of sodium, increase of potassium, and decrease of the total osmotic cortico-papillary gradient of the kidney. No loss of Na+ and K+-ATPase activity occurred under these conditions. The determination of Na+ and K+-ATPase level in the renal tissue turns out to be a rational method to assess the vitality of an organ to be transplanted."}
{"id": "PMID:216173", "title": "[Enzymatic and morphologic studies on long-term perfused dog kidneys].", "content": "21 canine and 12 human kidneys were submitted to long-term perfusion for 24 hours. During that time LDH-activity, histologic, enzyme-histochemic, and ultrastructural examinations were carried out. The findings proved that kidneys with lesser damage from ischemia showed lower activities during the first 4 to 6 hours than kidneys which were more injured before. The latter showed the same ultrastructural alterations as kidneys after perfusion for 24 hours, which suggests an irreversible partial damage of the organ.", "contents": "[Enzymatic and morphologic studies on long-term perfused dog kidneys]. 21 canine and 12 human kidneys were submitted to long-term perfusion for 24 hours. During that time LDH-activity, histologic, enzyme-histochemic, and ultrastructural examinations were carried out. The findings proved that kidneys with lesser damage from ischemia showed lower activities during the first 4 to 6 hours than kidneys which were more injured before. The latter showed the same ultrastructural alterations as kidneys after perfusion for 24 hours, which suggests an irreversible partial damage of the organ."}
{"id": "PMID:216174", "title": "[In-vitro inhibition of collagenase activity in epidermolysis bullosa hereditaria dystrophica].", "content": "By means of a biological collagenase assay we estimated collagenolytic activity of the vesicular fluid of patients with epidermolysis bullosa hereditaria dystrophica. All the 5 examined patients showed increased collagenolysis. Inhibition studies were performed applying ethylendiaminetetraacetate inhibition 11,15%, normal human serum in 12.15% (means). o-Phenanthroline as well as erythromycine in an aequimolar ratio stopped the collagenolytic activity completely in the 5 specimen. It was the aim of our study to indicate that erythromycine, in contrast to other collagenase inhibitors relatively atoxic, is able to inhibit collagenase activity which is suggested to play a pathogenetic role in that disease.", "contents": "[In-vitro inhibition of collagenase activity in epidermolysis bullosa hereditaria dystrophica]. By means of a biological collagenase assay we estimated collagenolytic activity of the vesicular fluid of patients with epidermolysis bullosa hereditaria dystrophica. All the 5 examined patients showed increased collagenolysis. Inhibition studies were performed applying ethylendiaminetetraacetate inhibition 11,15%, normal human serum in 12.15% (means). o-Phenanthroline as well as erythromycine in an aequimolar ratio stopped the collagenolytic activity completely in the 5 specimen. It was the aim of our study to indicate that erythromycine, in contrast to other collagenase inhibitors relatively atoxic, is able to inhibit collagenase activity which is suggested to play a pathogenetic role in that disease."}
{"id": "PMID:216175", "title": "[Prognostic significance of follow-up scintigraphy with 99m Tc-pyrophosphate in myocardial infarction (author's transl)].", "content": "Using 99m Tc-pyrophosphate there is a positive visualization of a transmural myocardial infarction by a localized tracer activity outside of the skeletal system. The uptake of the tracer in the infarcted area is expressed as percentage of the accumulation over the sternum. It reaches a maximum 48-60 hours after infarct onset and then recedes gradually but not strictly linearly. On the occasion of a control scintigraphy 3-4 weeks after the myocardial infarction and after full mobilization 56 per cent of the investigated patients showed a variable decrease of the tracer activity. On 44 per cent the tracer activity in the infarcted area remained unchanged or even increased slightly, though the infarction could be excluded. At the same time performed haemodynamic investigations with measuring the pulmonary artery pressure at rest and under stress conditions showed a good correlation between the persistence of the tracer activity in the infarcted area and the amount of the pulmonary pressure at rest and during stress, manifesting left ventricular function. So the result of a control scintigraphy 3-4 weeks after myocardial infarction allows to draw prognostic inferences about the further course of the disease.", "contents": "[Prognostic significance of follow-up scintigraphy with 99m Tc-pyrophosphate in myocardial infarction (author's transl)]. Using 99m Tc-pyrophosphate there is a positive visualization of a transmural myocardial infarction by a localized tracer activity outside of the skeletal system. The uptake of the tracer in the infarcted area is expressed as percentage of the accumulation over the sternum. It reaches a maximum 48-60 hours after infarct onset and then recedes gradually but not strictly linearly. On the occasion of a control scintigraphy 3-4 weeks after the myocardial infarction and after full mobilization 56 per cent of the investigated patients showed a variable decrease of the tracer activity. On 44 per cent the tracer activity in the infarcted area remained unchanged or even increased slightly, though the infarction could be excluded. At the same time performed haemodynamic investigations with measuring the pulmonary artery pressure at rest and under stress conditions showed a good correlation between the persistence of the tracer activity in the infarcted area and the amount of the pulmonary pressure at rest and during stress, manifesting left ventricular function. So the result of a control scintigraphy 3-4 weeks after myocardial infarction allows to draw prognostic inferences about the further course of the disease."}
{"id": "PMID:216177", "title": "Ultrastructural alterations and peroxide formation induced by naphthoquinones in different stages of Trypanosoma cruzi.", "content": "Addition of beta-lapachone, an o-naphthoquinone with bactericidal, cytotoxic, and trypanocidal activities, to Trypanosoma cruzi epimastigote and amastigote stages induced the release of O2- and H2O2 from the whole cells into the suspending medium. In the presence of reduced nicotinamide adenine dinucleotide as reductant beta-lapachone was also able to stimulate O2- and H2O2 production by homogenates of these stages. Electron micrographs showed that in beta-lapachone-treated amastigotes and trypomastigotes, the chromatin is arranged in patches, clearly differing from the normal pattern of chromatin distribution. Alterations of the nuclear, mitochondrial, and cytoplasmic membranes, as well as swelling of the mitochondria were also observed.", "contents": "Ultrastructural alterations and peroxide formation induced by naphthoquinones in different stages of Trypanosoma cruzi. Addition of beta-lapachone, an o-naphthoquinone with bactericidal, cytotoxic, and trypanocidal activities, to Trypanosoma cruzi epimastigote and amastigote stages induced the release of O2- and H2O2 from the whole cells into the suspending medium. In the presence of reduced nicotinamide adenine dinucleotide as reductant beta-lapachone was also able to stimulate O2- and H2O2 production by homogenates of these stages. Electron micrographs showed that in beta-lapachone-treated amastigotes and trypomastigotes, the chromatin is arranged in patches, clearly differing from the normal pattern of chromatin distribution. Alterations of the nuclear, mitochondrial, and cytoplasmic membranes, as well as swelling of the mitochondria were also observed."}
{"id": "PMID:216176", "title": "Dependence of cellular surface area on growth density of 3T3 and SV40-3T3 cells.", "content": "The cell surface areas of 3T3 and SV40-3T3 cells both for suspended and for flat cells growing on the culture substrate have been determined in dependence on growth density. The surface areas of flat 3T3 and SV40-3T3 cells turn out to be independent of growth density over a wide range. For 3T3 cells the surface area of flat cells compares well with that determined by Collard and Temmink for suspended 3T3 cells taking the surface area of their coverlayer of microvilli into account. This indicates that upon suspension of flat 3T3 cells the surplus surface area is disposed of in the form of microvilli. For SV40-3T3 cells we obtained a surface area of flat cells which differs by a factor of about two from that of suspended cells as determined by Collard and Temmink including the surface area of microvilli. Microscopical diameters and electrical (\"Coulter\") volumina of suspended 3T3 and SV40-3T3 cells depend only little on cell density in the range investigated.", "contents": "Dependence of cellular surface area on growth density of 3T3 and SV40-3T3 cells. The cell surface areas of 3T3 and SV40-3T3 cells both for suspended and for flat cells growing on the culture substrate have been determined in dependence on growth density. The surface areas of flat 3T3 and SV40-3T3 cells turn out to be independent of growth density over a wide range. For 3T3 cells the surface area of flat cells compares well with that determined by Collard and Temmink for suspended 3T3 cells taking the surface area of their coverlayer of microvilli into account. This indicates that upon suspension of flat 3T3 cells the surplus surface area is disposed of in the form of microvilli. For SV40-3T3 cells we obtained a surface area of flat cells which differs by a factor of about two from that of suspended cells as determined by Collard and Temmink including the surface area of microvilli. Microscopical diameters and electrical (\"Coulter\") volumina of suspended 3T3 and SV40-3T3 cells depend only little on cell density in the range investigated."}
{"id": "PMID:216186", "title": "[Benign and malignant synovialoma (author's transl)].", "content": "Synovialomas are rare tumorus. Their histology is as difficult as assessing their prognosis. Benign synovialomas should be extirpated radically. In case of malignancy amputation should be performed immediately, because amputation not until the first recurrence will often come too late. Only this treatment plan offers at present a chance to lower the otherwise high mortality rate.", "contents": "[Benign and malignant synovialoma (author's transl)]. Synovialomas are rare tumorus. Their histology is as difficult as assessing their prognosis. Benign synovialomas should be extirpated radically. In case of malignancy amputation should be performed immediately, because amputation not until the first recurrence will often come too late. Only this treatment plan offers at present a chance to lower the otherwise high mortality rate."}
{"id": "PMID:216187", "title": "[Characterization of plasmid DNA in a lecithinase-positive and in a lecithinase-negative strain of Clostridium perfringens (author's transl)].", "content": "A non pathogenic variant of Clostridium perfringens and the wild type strain were characterized. The strains agreed in most of the biochemical properties, in susceptibility against antibiotics and in bacteriocin production. Contrary to the wild type the variant did not produce lecithinase and gelatinase. In deoxyribonucleic acid (DNA) of both strains centrifuged in cesiumchlorid-ethidiumbromide equilibrium there was found a satellite peak containing three distinct, covalently closed circular (CCC) DNA elements. The sum of the average molecular weight or contour length of the two small circular molecules was equal to the average molecular weight or contour length of the third. The presence of the plasmids in the variant indicated that the synthesis of lecithinase might not be coded by a plasmid.", "contents": "[Characterization of plasmid DNA in a lecithinase-positive and in a lecithinase-negative strain of Clostridium perfringens (author's transl)]. A non pathogenic variant of Clostridium perfringens and the wild type strain were characterized. The strains agreed in most of the biochemical properties, in susceptibility against antibiotics and in bacteriocin production. Contrary to the wild type the variant did not produce lecithinase and gelatinase. In deoxyribonucleic acid (DNA) of both strains centrifuged in cesiumchlorid-ethidiumbromide equilibrium there was found a satellite peak containing three distinct, covalently closed circular (CCC) DNA elements. The sum of the average molecular weight or contour length of the two small circular molecules was equal to the average molecular weight or contour length of the third. The presence of the plasmids in the variant indicated that the synthesis of lecithinase might not be coded by a plasmid."}
{"id": "PMID:216188", "title": "Phosphatase activity of aerobic and facultative anaerobic bacteria.", "content": "1115 strains of aerobic and facultatively anaerobic bacteria were tested for phosphatase activity by a conventional plate method and a microtest. The microtest was devised to allow results to be read after 4 h cultivation. Phosphatase activity was found in wide range of species and strains. Besides staphylococci, where the test for phosphatase is successfully used, it may be applied as one of the valuable tests for the differentiation of the following species: Bacillus cereus, B. licheniformis, Aeromonas spp., Vibrio parahaemolyticus, Actinobacillus spp., Pasteurella spp., Xanthomonas spp., Flavobacterium spp., Alteromonas putrefaciens, Pseudomonas maltophilia, Ps. cepacia, and some other species of Pseudomonas. The species which gave uniformly negative phosphatase reaction were as follows: Staph. saprophyticus, Acinetobacter calcoaceticus, Alcaligenes faecalis, and Bordetella bronchiseptica.", "contents": "Phosphatase activity of aerobic and facultative anaerobic bacteria. 1115 strains of aerobic and facultatively anaerobic bacteria were tested for phosphatase activity by a conventional plate method and a microtest. The microtest was devised to allow results to be read after 4 h cultivation. Phosphatase activity was found in wide range of species and strains. Besides staphylococci, where the test for phosphatase is successfully used, it may be applied as one of the valuable tests for the differentiation of the following species: Bacillus cereus, B. licheniformis, Aeromonas spp., Vibrio parahaemolyticus, Actinobacillus spp., Pasteurella spp., Xanthomonas spp., Flavobacterium spp., Alteromonas putrefaciens, Pseudomonas maltophilia, Ps. cepacia, and some other species of Pseudomonas. The species which gave uniformly negative phosphatase reaction were as follows: Staph. saprophyticus, Acinetobacter calcoaceticus, Alcaligenes faecalis, and Bordetella bronchiseptica."}
{"id": "PMID:216183", "title": "Purification and some properties of collagenase proenzyme activator from rheumatoid synovial fluid.", "content": "1. An activator of leucocyte latent collagenase has been extracted from rheumatoid synovial fluid by a preparative method consisting of six steps including precipitation by ammonium sulphate and chromatography on Sephadex G-100, QAE-Sephadex and SP-Sephadex C-50. The purification factor was nearly 1000 and the activator isolated could be shown to have a high degree of homogeneity.--2. Gel chromatography indicated a molecular weight of ca. 60 000.--3. Kinetic studies of the activation and inactivation of the activator during incubation at higher temperatures demonstrated its enzymic nature.--4. Activation of latent collagenase was partially inhibited by iPr2P-F and KCN. Soybean trypsin inhibitor, iodoacetamide, TosLysCH2Cl and TosPheCH2Cl had no effect.--5. Leucocyte latent collagenase was also activated by an excess of trypsin and p-hydroxymercuribenzenesulphonic acid, but only to the extent of about 40% of its activation capacity. Purified neutral protease from human leucocyte granules had no effect on latent collagenase.--6. Several typical substrates for proteases, peptidases, esterases and glycosidases were not attacked by the activator. The possibility that the activator is a known enzyme, such as kallikrein, urokinase or cathepsin B1, could be excluded.", "contents": "Purification and some properties of collagenase proenzyme activator from rheumatoid synovial fluid. 1. An activator of leucocyte latent collagenase has been extracted from rheumatoid synovial fluid by a preparative method consisting of six steps including precipitation by ammonium sulphate and chromatography on Sephadex G-100, QAE-Sephadex and SP-Sephadex C-50. The purification factor was nearly 1000 and the activator isolated could be shown to have a high degree of homogeneity.--2. Gel chromatography indicated a molecular weight of ca. 60 000.--3. Kinetic studies of the activation and inactivation of the activator during incubation at higher temperatures demonstrated its enzymic nature.--4. Activation of latent collagenase was partially inhibited by iPr2P-F and KCN. Soybean trypsin inhibitor, iodoacetamide, TosLysCH2Cl and TosPheCH2Cl had no effect.--5. Leucocyte latent collagenase was also activated by an excess of trypsin and p-hydroxymercuribenzenesulphonic acid, but only to the extent of about 40% of its activation capacity. Purified neutral protease from human leucocyte granules had no effect on latent collagenase.--6. Several typical substrates for proteases, peptidases, esterases and glycosidases were not attacked by the activator. The possibility that the activator is a known enzyme, such as kallikrein, urokinase or cathepsin B1, could be excluded."}
{"id": "PMID:216189", "title": "Morphological and physical characteristics of an antigen associated with viral hepatitis type A (Botevgrad antigen).", "content": "Immune electron microscopy (IEM) was employed in studying faecal samples of viral hepatitis type A patients and their contacts, in whom the presence of an antigen, differing from the HBsAg, designated as Botevgrad antigen (BA) was proved by the CFT. Particles 25--28 nm in diameter, aggregated by sera positive for the anti-HAAg were established in the faecal samples. The buoyant density of these particles in CsCl was found to be 1.40 g/ml. Particles of the same buoyant density were established also in sera positive for BA which were aggregated in large masses with antiserum against BA obtained from rabbits. The associations between BA and HAAg are discussed.", "contents": "Morphological and physical characteristics of an antigen associated with viral hepatitis type A (Botevgrad antigen). Immune electron microscopy (IEM) was employed in studying faecal samples of viral hepatitis type A patients and their contacts, in whom the presence of an antigen, differing from the HBsAg, designated as Botevgrad antigen (BA) was proved by the CFT. Particles 25--28 nm in diameter, aggregated by sera positive for the anti-HAAg were established in the faecal samples. The buoyant density of these particles in CsCl was found to be 1.40 g/ml. Particles of the same buoyant density were established also in sera positive for BA which were aggregated in large masses with antiserum against BA obtained from rabbits. The associations between BA and HAAg are discussed."}
{"id": "PMID:216198", "title": "Cyclic AMP and its functional relationship in Tetrahymena: a comparison between phagocytosis and glucose uptake.", "content": "In Tetrahymena, an increase in the level of cAMP is accompanied by an increased phagocytotic rate, whereas increased sugar uptake is parallelled by a decreased cAMP level. The increase in cAMP level seems to be decisive with respect to phagocytosis as a basic phenomenon of life. In the action of epinephrine, however, some mechanism other than cAMP mediation may be involved. Depending on concentration, one hormone may provoke either an increase or a decrease in cAMP level, and this in turn triggers the corresponding function.", "contents": "Cyclic AMP and its functional relationship in Tetrahymena: a comparison between phagocytosis and glucose uptake. In Tetrahymena, an increase in the level of cAMP is accompanied by an increased phagocytotic rate, whereas increased sugar uptake is parallelled by a decreased cAMP level. The increase in cAMP level seems to be decisive with respect to phagocytosis as a basic phenomenon of life. In the action of epinephrine, however, some mechanism other than cAMP mediation may be involved. Depending on concentration, one hormone may provoke either an increase or a decrease in cAMP level, and this in turn triggers the corresponding function."}
{"id": "PMID:216195", "title": "[Comparative study of the fatty acid composition of glycerophosphatides from whole vertebrate brain and portions of it].", "content": "Fatty acids of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and monophosphoinositide were studied in the whole brain, in the forebrain and the brain stem in the frog Rana temporaria, tortoise Emys orbicularis, hen and cat. Every family of phospholipids (PL) possesses a characteristic fatty acid pattern irrespectively of the brain part. There are regular topologic differences in the fatty acid composition of PL, namely the relative amount of saturated and polyenoic acids is higher and that of monoenoic acids lower in the forebrain as compared to the brain stem. The increase in the relative size of the forebrain, occurring in the evolution of vertebrate brain, exerts a definite influence on the fatty acid composition of the total brain. Nevertheless this increase in the size of the forebrain does not solely determine the fatty acid composition of the total brain. Similar changes are occurring in all brain parts: the relative amount of saturated fatty acids of PL is increasing and that of unsaturated acids decreasing. The evolutionary deductions derived from the biochemical study of the total brain find confirmation in the investigation of the brain parts.", "contents": "[Comparative study of the fatty acid composition of glycerophosphatides from whole vertebrate brain and portions of it]. Fatty acids of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and monophosphoinositide were studied in the whole brain, in the forebrain and the brain stem in the frog Rana temporaria, tortoise Emys orbicularis, hen and cat. Every family of phospholipids (PL) possesses a characteristic fatty acid pattern irrespectively of the brain part. There are regular topologic differences in the fatty acid composition of PL, namely the relative amount of saturated and polyenoic acids is higher and that of monoenoic acids lower in the forebrain as compared to the brain stem. The increase in the relative size of the forebrain, occurring in the evolution of vertebrate brain, exerts a definite influence on the fatty acid composition of the total brain. Nevertheless this increase in the size of the forebrain does not solely determine the fatty acid composition of the total brain. Similar changes are occurring in all brain parts: the relative amount of saturated fatty acids of PL is increasing and that of unsaturated acids decreasing. The evolutionary deductions derived from the biochemical study of the total brain find confirmation in the investigation of the brain parts."}
{"id": "PMID:216196", "title": "[Clinical forms of glomus tumors of the temporal bone and base of the skull].", "content": "On the basis of the clinical examination of 99 patients, researchers distinguished the clinical forms of the glomus tumour of the temporal bone and of the base of the skull: glomus jugulare tumour, tympanic glomus, glomus of the pyramid of the temporal bone, glomus of the vagus nerve. Every clinical form is characterized both by general symptoms and by signs which appear only with the given form. The peculiarity of the clinical course of glomus tumours is due to intracranial growth, malignization and also by recurrence and prolonged growth.", "contents": "[Clinical forms of glomus tumors of the temporal bone and base of the skull]. On the basis of the clinical examination of 99 patients, researchers distinguished the clinical forms of the glomus tumour of the temporal bone and of the base of the skull: glomus jugulare tumour, tympanic glomus, glomus of the pyramid of the temporal bone, glomus of the vagus nerve. Every clinical form is characterized both by general symptoms and by signs which appear only with the given form. The peculiarity of the clinical course of glomus tumours is due to intracranial growth, malignization and also by recurrence and prolonged growth."}
{"id": "PMID:216199", "title": "The cytologic diagnosis of breast aspirations.", "content": "A series of 1,792 breast cytology specimens were evaluated from the Boston Hospital for Women for the years 1970-1974. The majority (1,684) were needle aspiration smears, the remainder (108) were nipple secretion smears. The cytologic criteria for diagnosing breast specimens were presented. Of the 1,792 breast specimens examined cytologically, 48 cases were histologically proven cancers with 33 smears containing malignant or suspicious cells, indicating 92% accuracy (after correction for unsatisfactory smears). A suspicious or positive interpretation of the smears prompted a biopsy and led to early diagnosis. Although needle aspiration cytology is not a new technique, it is one which is economical, easy, accurate and lacking in complications to the patient. Hopefully in the near future, it will be a more widely accepted procedure for the early detection of breast cancer.", "contents": "The cytologic diagnosis of breast aspirations. A series of 1,792 breast cytology specimens were evaluated from the Boston Hospital for Women for the years 1970-1974. The majority (1,684) were needle aspiration smears, the remainder (108) were nipple secretion smears. The cytologic criteria for diagnosing breast specimens were presented. Of the 1,792 breast specimens examined cytologically, 48 cases were histologically proven cancers with 33 smears containing malignant or suspicious cells, indicating 92% accuracy (after correction for unsatisfactory smears). A suspicious or positive interpretation of the smears prompted a biopsy and led to early diagnosis. Although needle aspiration cytology is not a new technique, it is one which is economical, easy, accurate and lacking in complications to the patient. Hopefully in the near future, it will be a more widely accepted procedure for the early detection of breast cancer."}
{"id": "PMID:216200", "title": "Cytopathology of Paget's disease of the vulva. Diagnostic abrasive cytology.", "content": "The cytologic appearance of Paget's disease of the vulva is described, noting the similarity in appearance of the cells to those seen in Paget's disease of the nipple. The relation of this disease state to mammary involvement is emphasized by the fact that three of the five cases presenting had either a current or past history of breast ductal carcinoma or hyperplasia.", "contents": "Cytopathology of Paget's disease of the vulva. Diagnostic abrasive cytology. The cytologic appearance of Paget's disease of the vulva is described, noting the similarity in appearance of the cells to those seen in Paget's disease of the nipple. The relation of this disease state to mammary involvement is emphasized by the fact that three of the five cases presenting had either a current or past history of breast ductal carcinoma or hyperplasia."}
{"id": "PMID:216203", "title": "Cytologic findings in a case of malignant fibrous histiocytoma.", "content": "Morphologic changes in malignant cells obtained by needle aspiration of a recurrent malignant fibrous histiocytoma of the left axilla in a 61 year old male are reported. Basically, two types of cells are described: pleomorphic malignant histiocytic cells with marked phagocytic activity and sarcomatous spindle cells. Intermediate forms with features of both types are identified.", "contents": "Cytologic findings in a case of malignant fibrous histiocytoma. Morphologic changes in malignant cells obtained by needle aspiration of a recurrent malignant fibrous histiocytoma of the left axilla in a 61 year old male are reported. Basically, two types of cells are described: pleomorphic malignant histiocytic cells with marked phagocytic activity and sarcomatous spindle cells. Intermediate forms with features of both types are identified."}
{"id": "PMID:216204", "title": "Nuclear DNA content of trophoblastic tumors.", "content": "The nuclear DNA content of trophoblasts was measured in 25 cases of normal pregnancy, 46 cases with hydatidiform mole, ten cases with destructive mole and six cases of chorionepithelioma (choriocarcinoma). In normal pregnancy, DNA distribution in syncytiotrophoblasts and cytotrophoblasts showed a sharp peak at the diploid region, although a few cytotrophoblasts with increased DNA content were observed in the first trimester. In chorionepithelioma the DNA content of the trophoblastic cells showed extremely wide distribution without any special peak. In destructive mole, although a wide distribution was observed, the sharp peak was usually noted at the diploid range. Cases with hydatidiform mole were divided into two categories according to the DNA distribution patterns. Type I showed the patterns similar to the first trimester of normal pregnancy and type II resembled the patterns of destructive mole. In hydatidiform mole of type II, subsequent progress towards destructive mole was frequently encountered.", "contents": "Nuclear DNA content of trophoblastic tumors. The nuclear DNA content of trophoblasts was measured in 25 cases of normal pregnancy, 46 cases with hydatidiform mole, ten cases with destructive mole and six cases of chorionepithelioma (choriocarcinoma). In normal pregnancy, DNA distribution in syncytiotrophoblasts and cytotrophoblasts showed a sharp peak at the diploid region, although a few cytotrophoblasts with increased DNA content were observed in the first trimester. In chorionepithelioma the DNA content of the trophoblastic cells showed extremely wide distribution without any special peak. In destructive mole, although a wide distribution was observed, the sharp peak was usually noted at the diploid range. Cases with hydatidiform mole were divided into two categories according to the DNA distribution patterns. Type I showed the patterns similar to the first trimester of normal pregnancy and type II resembled the patterns of destructive mole. In hydatidiform mole of type II, subsequent progress towards destructive mole was frequently encountered."}
{"id": "PMID:216201", "title": "Corpora amylacea in cerebrospinal fluid. A source of possible diagnostic error.", "content": "Corpora amylacea in the central and peripheral nervous system are round, amorphous intracellular bodies which are frequently found in large numbers around the ventricles of elderly individuals. These bodies were recently identified in a cytologic preparation of ventricular fluid. Although they have no known diagnostic significance, their possible confusion with yeast forms makes recognition of these structures important.", "contents": "Corpora amylacea in cerebrospinal fluid. A source of possible diagnostic error. Corpora amylacea in the central and peripheral nervous system are round, amorphous intracellular bodies which are frequently found in large numbers around the ventricles of elderly individuals. These bodies were recently identified in a cytologic preparation of ventricular fluid. Although they have no known diagnostic significance, their possible confusion with yeast forms makes recognition of these structures important."}
{"id": "PMID:216208", "title": "Studies on cyclic nucleotides in the adrenal gland. IX. Effects of ACTH on cyclic AMP and steroid production by the zona fasciculata-reticularis of the adrenal cortex.", "content": "Effects of ACTH and calcium on cyclic AMP and steroid production by the zona fasciculata-reticularis (the decapsulated fraction) from the rat adrenal cortex have been studied. Increasing concentrations of extracellular calcium enhanced the action of ACTH on cyclic AMP and steroid production. These effects of ACTH with calcium were prevented by lanthanum, but not by tetracaine or verapamil, suggesting that ACTH stimulation may be mediated by calcium through a process not involving the tetracaine- or verapamil-vulnerable step(s) of the calcium current. High concentrations of external calcium itself increased cyclic AMP accumulation without any increase in steroidogenesis. A calcium ionophore, X537A was stimulatory for steroidogenesis but inhibitory with respect to cyclic AMP accumulation. Considered together with the findings of AMP increase, these results suggest that ACTH primarily increases intracellular calcium mobilization thus stimulating directly the steroidogenesis, which is independent of the cyclic AMP system. Relatively high concentrations of ACTH activate the adenylate cyclase, which depends on extracellular calcium to increase cyclic AMP levels and stimulation of steroidogenesis by the decapsulated fractions of the adrenal cortex.", "contents": "Studies on cyclic nucleotides in the adrenal gland. IX. Effects of ACTH on cyclic AMP and steroid production by the zona fasciculata-reticularis of the adrenal cortex. Effects of ACTH and calcium on cyclic AMP and steroid production by the zona fasciculata-reticularis (the decapsulated fraction) from the rat adrenal cortex have been studied. Increasing concentrations of extracellular calcium enhanced the action of ACTH on cyclic AMP and steroid production. These effects of ACTH with calcium were prevented by lanthanum, but not by tetracaine or verapamil, suggesting that ACTH stimulation may be mediated by calcium through a process not involving the tetracaine- or verapamil-vulnerable step(s) of the calcium current. High concentrations of external calcium itself increased cyclic AMP accumulation without any increase in steroidogenesis. A calcium ionophore, X537A was stimulatory for steroidogenesis but inhibitory with respect to cyclic AMP accumulation. Considered together with the findings of AMP increase, these results suggest that ACTH primarily increases intracellular calcium mobilization thus stimulating directly the steroidogenesis, which is independent of the cyclic AMP system. Relatively high concentrations of ACTH activate the adenylate cyclase, which depends on extracellular calcium to increase cyclic AMP levels and stimulation of steroidogenesis by the decapsulated fractions of the adrenal cortex."}
{"id": "PMID:216205", "title": "The cell concentration method using acetylcysteine for sputum cytology.", "content": "In order to improve the results of cytologic diagnosis of pulmonary carcinoma, a technique for concentrating cells from sputum using acetylcysteine was developed. Using the same sputum specimens, the rate of positive cytologic diagnosis of pulmonary carcinoma by this method was increased by 22.6% over the level achieved by the direct smear method. This cell concentration method improved the rate of positive diagnosis in peripheral type pulmonary carcinoma and particularly in adenocarcinoma. The cell concentration method using acetylcysteine shows great promise in the cytologic diagnosis of sputum specimens.", "contents": "The cell concentration method using acetylcysteine for sputum cytology. In order to improve the results of cytologic diagnosis of pulmonary carcinoma, a technique for concentrating cells from sputum using acetylcysteine was developed. Using the same sputum specimens, the rate of positive cytologic diagnosis of pulmonary carcinoma by this method was increased by 22.6% over the level achieved by the direct smear method. This cell concentration method improved the rate of positive diagnosis in peripheral type pulmonary carcinoma and particularly in adenocarcinoma. The cell concentration method using acetylcysteine shows great promise in the cytologic diagnosis of sputum specimens."}
{"id": "PMID:216202", "title": "Synovial sarcoma diagnosed by fine-needle aspiration biopsy. A case report.", "content": "The cytologic findings of a synovial sarcoma are described. A 60 year old male had felt a slowly growing tumor in his right sole for three years. From the first fine-needle aspiration biopsy a fibrosarcoma or other mesenchymal tumor was suggested; but the second biopsy showed both fibrosarcoma and mesothelial-like cells in contact with each other, and the diagnosis of synovial sarcoma was made. Histologic and electron microscopic sections confirmed the diagnosis. In the differential diagnosis of this case, fibrosarcoma and other malignant mesenchymal tumors were considered. The applicability of fine-needle aspiration biopsy in mesenchymal lesions is discussed.", "contents": "Synovial sarcoma diagnosed by fine-needle aspiration biopsy. A case report. The cytologic findings of a synovial sarcoma are described. A 60 year old male had felt a slowly growing tumor in his right sole for three years. From the first fine-needle aspiration biopsy a fibrosarcoma or other mesenchymal tumor was suggested; but the second biopsy showed both fibrosarcoma and mesothelial-like cells in contact with each other, and the diagnosis of synovial sarcoma was made. Histologic and electron microscopic sections confirmed the diagnosis. In the differential diagnosis of this case, fibrosarcoma and other malignant mesenchymal tumors were considered. The applicability of fine-needle aspiration biopsy in mesenchymal lesions is discussed."}
{"id": "PMID:216209", "title": "Plasma cyclic nucleotide levels in hyperthyroidism.", "content": "Plasma cyclic AMP and cyclic GMP levels were studied in a group of normal subjects and 10 subjects with hyperthyroidism. In the control group, mean plasma cyclic AMP levels were 15.3 +/- 1.3 nmol/l (SEM), and plasma cyclic GMP levels were 9.4 +/- 0.58 nmol/l (SEM). In untreated hyperthyroid subjects, both plasma cyclic AMP and cyclic GMP levels were significantly elevated above normal with mean values of 35.0 +/- 2.4 nmol/l (SEM) (P less than 0.001) and 14.7 +/- 0.2 nmol/l (SEM), (P less than 0.001), respectively. Six of the hyperthyroid subjects were re-studied when they became euthyroid; plasma cyclic nucleotide concentrations all fell within the normal range. To evaluate the relative contribution of triiodothyronine and thyroxine to elevated plasma cyclic nucleotide levels, two hyperthyroid subjects were treated with propylthiouracil and iodide. Plasma cyclic nucleotide levels were normalized when plasma triiodothyronine levels declined to normal range, at the time when plasma thyroxine levels were still elevated. These preliminary data suggest that increased triiodothyronine production is responsible for the increased cyclic nucleotide levels in hyperthyroidism.", "contents": "Plasma cyclic nucleotide levels in hyperthyroidism. Plasma cyclic AMP and cyclic GMP levels were studied in a group of normal subjects and 10 subjects with hyperthyroidism. In the control group, mean plasma cyclic AMP levels were 15.3 +/- 1.3 nmol/l (SEM), and plasma cyclic GMP levels were 9.4 +/- 0.58 nmol/l (SEM). In untreated hyperthyroid subjects, both plasma cyclic AMP and cyclic GMP levels were significantly elevated above normal with mean values of 35.0 +/- 2.4 nmol/l (SEM) (P less than 0.001) and 14.7 +/- 0.2 nmol/l (SEM), (P less than 0.001), respectively. Six of the hyperthyroid subjects were re-studied when they became euthyroid; plasma cyclic nucleotide concentrations all fell within the normal range. To evaluate the relative contribution of triiodothyronine and thyroxine to elevated plasma cyclic nucleotide levels, two hyperthyroid subjects were treated with propylthiouracil and iodide. Plasma cyclic nucleotide levels were normalized when plasma triiodothyronine levels declined to normal range, at the time when plasma thyroxine levels were still elevated. These preliminary data suggest that increased triiodothyronine production is responsible for the increased cyclic nucleotide levels in hyperthyroidism."}
{"id": "PMID:216210", "title": "Immunoreactive beta-MSH in human plasma and in a corticotrophic adenoma culture medium. Its relation to the lipotrophins.", "content": "In order to characterize more accurately the relationship between immunoreactive beta-MSH (\"BETA-MSH\") and the lipotrophins (LPH) we attempted to investigate the gel filtration and the immunological characteristics of \"beta-MSH\" in the plasma of patients with Nelson's syndrome and Addison's disease as well as in the culture medium from a human corticotrophic adenoma using a sensitive radioimmunoassay from human beta-MSH. When added either to hormone free plasma or to a plasma from a patient with Nelson's syndrome all the human beta-MSH (hbeta-MSH) elutes from a Sephadex G-50 column as a single peak in a volume corresponding to its molecular weight. In contrast plasma \"beta-MSH\" in 3 patients with Nelson's syndrome and one patient with Addison's disease almost completely elutes in a volume corresponding to a molecular weight range of 6000-10 000; no \"beta-MSH\" can be detected in its normal elution volume. Drastic pH change (8.2 to 2.3) does not significantly alter the elution pattern. Chromatography of a corticotrophic adenoma culture medium gave a similar pattern of \"beta-MSH\" with a main peak in the molecular weight range of 6000-10 000. In our radioimmunoassay the culture medium and purified hbeta-LPH gave parallel displacement curves for [125I]hbeta-MSH. It is suggested that hbeta-LPH or a closely related substance is the main material responsible for \"beta-MSH\" immunoactivity.", "contents": "Immunoreactive beta-MSH in human plasma and in a corticotrophic adenoma culture medium. Its relation to the lipotrophins. In order to characterize more accurately the relationship between immunoreactive beta-MSH (\"BETA-MSH\") and the lipotrophins (LPH) we attempted to investigate the gel filtration and the immunological characteristics of \"beta-MSH\" in the plasma of patients with Nelson's syndrome and Addison's disease as well as in the culture medium from a human corticotrophic adenoma using a sensitive radioimmunoassay from human beta-MSH. When added either to hormone free plasma or to a plasma from a patient with Nelson's syndrome all the human beta-MSH (hbeta-MSH) elutes from a Sephadex G-50 column as a single peak in a volume corresponding to its molecular weight. In contrast plasma \"beta-MSH\" in 3 patients with Nelson's syndrome and one patient with Addison's disease almost completely elutes in a volume corresponding to a molecular weight range of 6000-10 000; no \"beta-MSH\" can be detected in its normal elution volume. Drastic pH change (8.2 to 2.3) does not significantly alter the elution pattern. Chromatography of a corticotrophic adenoma culture medium gave a similar pattern of \"beta-MSH\" with a main peak in the molecular weight range of 6000-10 000. In our radioimmunoassay the culture medium and purified hbeta-LPH gave parallel displacement curves for [125I]hbeta-MSH. It is suggested that hbeta-LPH or a closely related substance is the main material responsible for \"beta-MSH\" immunoactivity."}
{"id": "PMID:216213", "title": "Spontaneous rosette formation in vitro under the effect of agents affecting the cyclic nucleotide system of circulating lymphocytes of normal subjects.", "content": "Aminophylline was found to effect the early and total rosette-forming capacity of human thymus-dependent lymphocytes. This may be connected with an increase in the intracellular cyclic adenosine 3',5'-monophosphate level. Acetylcholine increases the proportion of early spontaneous rosettes, a phenomenon suggestive of a shift within the lymphocyte population toward a subpopulation of higher activity. The effect of acetylcholine is possibly mediated by an increase in the intracellular cyclic guanosine 3'-, 5'-monophosphate level. Aminophylline affects only the early rosette-forming capacity of thymus-derived lymphocytes. Levamisole has no influence on either early or total rosette-forming capacity of normal lymphocytes. The results are suggestive of definite relationships between the functional state, activity and cyclic nucleotide system of thymus-dependent lymphocytes.", "contents": "Spontaneous rosette formation in vitro under the effect of agents affecting the cyclic nucleotide system of circulating lymphocytes of normal subjects. Aminophylline was found to effect the early and total rosette-forming capacity of human thymus-dependent lymphocytes. This may be connected with an increase in the intracellular cyclic adenosine 3',5'-monophosphate level. Acetylcholine increases the proportion of early spontaneous rosettes, a phenomenon suggestive of a shift within the lymphocyte population toward a subpopulation of higher activity. The effect of acetylcholine is possibly mediated by an increase in the intracellular cyclic guanosine 3'-, 5'-monophosphate level. Aminophylline affects only the early rosette-forming capacity of thymus-derived lymphocytes. Levamisole has no influence on either early or total rosette-forming capacity of normal lymphocytes. The results are suggestive of definite relationships between the functional state, activity and cyclic nucleotide system of thymus-dependent lymphocytes."}
{"id": "PMID:216214", "title": "Effect of changes in cyclic nucleotide levels on human antibody-dependent cellular cytotoxicity.", "content": "The effect of agents influencing intracellular cyclic nucleotide levels and that of exogenous cAMP was studied on the cytotoxicity of normal human peripheral blood mononuclear cells on antibody coated human and chicken erythrocytes. Elevation of the cAMP level resulted in a marked decrease in cytotoxicity, while basically similar in the allogeneic and the xenogeneic test systems, but more expressed in the allogeneic system.", "contents": "Effect of changes in cyclic nucleotide levels on human antibody-dependent cellular cytotoxicity. The effect of agents influencing intracellular cyclic nucleotide levels and that of exogenous cAMP was studied on the cytotoxicity of normal human peripheral blood mononuclear cells on antibody coated human and chicken erythrocytes. Elevation of the cAMP level resulted in a marked decrease in cytotoxicity, while basically similar in the allogeneic and the xenogeneic test systems, but more expressed in the allogeneic system."}
{"id": "PMID:216215", "title": "In vitro effect of transfer factor on the cyclic nucleotide level of human lymphocytes in chronic lymphocytic leukaemia and of mouse lymphocytes.", "content": "In the present study transfer factor (TF) failed to produce any change in the cAMP- and cGMP-levels of lymphocytes of patients with chronic lymphoid leukaemia (CLL). This is attributed to the malignant transformation of the lymphocytes or to a changed proportion of different lymphocyte populations in CLL. Human TF leaves the cyclic nucleotide levels of splenic lymphocytes of BALB/c mice unaffected.", "contents": "In vitro effect of transfer factor on the cyclic nucleotide level of human lymphocytes in chronic lymphocytic leukaemia and of mouse lymphocytes. In the present study transfer factor (TF) failed to produce any change in the cAMP- and cGMP-levels of lymphocytes of patients with chronic lymphoid leukaemia (CLL). This is attributed to the malignant transformation of the lymphocytes or to a changed proportion of different lymphocyte populations in CLL. Human TF leaves the cyclic nucleotide levels of splenic lymphocytes of BALB/c mice unaffected."}
{"id": "PMID:216219", "title": "Influence of measles virus antigen on leukocyte migration in multiple sclerosis and controls.", "content": "The leukocyte migration inhibiton test was used in multiple sclerosis patients and in healthy controls for investigation of sensitization of blood lymphocytes against preparations of measles virus, mumps, NDV virus, and PPD. Regardless of antigen used, no significant differences were found between the groups. There was a strong correlation between the leukocyte migration inhibition obtained with measles virus antigen and with PPD. The leukocytes from MS patients as well as from healthy controls showed a significantly more pronounced inhibiton when a Tween 80 and ether-treated preparation of measles virus was used, compared with the whole measles virus antigen. No correlations were found between the degree of leukocyte migration inhibition and the antibody titers against different components of measles virus in individual samples.", "contents": "Influence of measles virus antigen on leukocyte migration in multiple sclerosis and controls. The leukocyte migration inhibiton test was used in multiple sclerosis patients and in healthy controls for investigation of sensitization of blood lymphocytes against preparations of measles virus, mumps, NDV virus, and PPD. Regardless of antigen used, no significant differences were found between the groups. There was a strong correlation between the leukocyte migration inhibition obtained with measles virus antigen and with PPD. The leukocytes from MS patients as well as from healthy controls showed a significantly more pronounced inhibiton when a Tween 80 and ether-treated preparation of measles virus was used, compared with the whole measles virus antigen. No correlations were found between the degree of leukocyte migration inhibition and the antibody titers against different components of measles virus in individual samples."}
{"id": "PMID:216220", "title": "A sporadic juvenile case of the amyotrophic lateral sclerosis with neuronal intracytoplasmic inclusions.", "content": "In an autopsy case of the sporadic juvenile ALS (a 17-year-old girl) intracytoplasmic inclusions are found in the upper and lower motor neurons and in nerve cells of the dentate nucleus, pontine nucleus, brain stem reticular formation, substantia nigra, thalamus, globus pallidus and others. Histochemically they contain RNA-Protein compounds. Electron microscopically, they consist of randomly interwoven tubules with granular endoplasmic reticulums and free ribosomes in the margin. Each tubule measures 90--150 A in diameter and shows no distinct periodic constiction. Amorphous substances as well as ribosome granules are scattered and associated with those tubules. The inclusion-bearing cells are usually swollen and chromatolytic and have a large hydropic nucleus, suggesting a close relation between the development of the inclusion and chromatolysis. Clinically, a rapid progress of the symptoms (total duration: about 12 months) and conspicuous disturbances of the autonomic nerve, such as sinus tachycardia and bladder sphincter dysfunction, should be noticed.", "contents": "A sporadic juvenile case of the amyotrophic lateral sclerosis with neuronal intracytoplasmic inclusions. In an autopsy case of the sporadic juvenile ALS (a 17-year-old girl) intracytoplasmic inclusions are found in the upper and lower motor neurons and in nerve cells of the dentate nucleus, pontine nucleus, brain stem reticular formation, substantia nigra, thalamus, globus pallidus and others. Histochemically they contain RNA-Protein compounds. Electron microscopically, they consist of randomly interwoven tubules with granular endoplasmic reticulums and free ribosomes in the margin. Each tubule measures 90--150 A in diameter and shows no distinct periodic constiction. Amorphous substances as well as ribosome granules are scattered and associated with those tubules. The inclusion-bearing cells are usually swollen and chromatolytic and have a large hydropic nucleus, suggesting a close relation between the development of the inclusion and chromatolysis. Clinically, a rapid progress of the symptoms (total duration: about 12 months) and conspicuous disturbances of the autonomic nerve, such as sinus tachycardia and bladder sphincter dysfunction, should be noticed."}
{"id": "PMID:216221", "title": "Lafora-like inclusion bodies in the CNS of aged dogs.", "content": "Forty randomly selected dogs, arranged into three groups according to age, were examined light and electron microscopically. Lafora-like inclusion bodies were found in all cases of aged dogs without neurological signs. They appeared as PAS positive, round bodies measuring up to 15 mu in diameter. Typically they had central cores and radiating peripheral lines. Electronmicroscopically, the inclusions consisted of irregularly clustered, short branching filaments measuring about 80--120 A in diameter or of electron-dense homogeneous or granular central cores with filamentous peripheral areas and located both in the perikarya and neuronal processes. The inclusions were disseminated all over the brain and spinal cord. The thalamic nuclei, a circumscribed area dorsal to the aqueduct, and the molecular layer of the superior colliculus were the most severely affected. The frequency of the inclusions showed age-dependency; the inclusions were not found in dogs younger than 2 years, but were extensive in all dogs of more than 8 years of age. The occurrence of the inclusions may therefore represent an age-dependent phenomenon. The relationship between the present findings and Lafora's disease is discussed.", "contents": "Lafora-like inclusion bodies in the CNS of aged dogs. Forty randomly selected dogs, arranged into three groups according to age, were examined light and electron microscopically. Lafora-like inclusion bodies were found in all cases of aged dogs without neurological signs. They appeared as PAS positive, round bodies measuring up to 15 mu in diameter. Typically they had central cores and radiating peripheral lines. Electronmicroscopically, the inclusions consisted of irregularly clustered, short branching filaments measuring about 80--120 A in diameter or of electron-dense homogeneous or granular central cores with filamentous peripheral areas and located both in the perikarya and neuronal processes. The inclusions were disseminated all over the brain and spinal cord. The thalamic nuclei, a circumscribed area dorsal to the aqueduct, and the molecular layer of the superior colliculus were the most severely affected. The frequency of the inclusions showed age-dependency; the inclusions were not found in dogs younger than 2 years, but were extensive in all dogs of more than 8 years of age. The occurrence of the inclusions may therefore represent an age-dependent phenomenon. The relationship between the present findings and Lafora's disease is discussed."}
{"id": "PMID:216222", "title": "Ultrastructural study of a patient with progressive dementia showing special intraplasmic inclusions in diffuse cerebral cortex. Mechanism of inclusions production.", "content": "Numerous inclusions were diffusely observed in the neurons and glial cells in the cerebral cortex of a patient with progressive dementia. These inclusions were initially produced by rough ER in the cells and gradually enlarged destroying the rough ER membranes. The nature of these inclusions was neutral mucopolysaccaride including protein histochemically. In the nuclei of the nerve cells and glial cells, some types of intranuclear virus-like inclusions were found. The first type was papova virus-like structure with high electron density measured 30--35 nm in diameter. The second type was paramyxovirus-like structure with granulo-fibrilar shape. The third type was large hexogonal core with high electron density measured 100 nm in diameter. These intranuclear virus-like bodies were not specific in the present case; however, it was speculated that intranuclear virus-like inclusions might have a deep relation to change the function of the nuclei and produced large intraplasmic inclusion bodies.", "contents": "Ultrastructural study of a patient with progressive dementia showing special intraplasmic inclusions in diffuse cerebral cortex. Mechanism of inclusions production. Numerous inclusions were diffusely observed in the neurons and glial cells in the cerebral cortex of a patient with progressive dementia. These inclusions were initially produced by rough ER in the cells and gradually enlarged destroying the rough ER membranes. The nature of these inclusions was neutral mucopolysaccaride including protein histochemically. In the nuclei of the nerve cells and glial cells, some types of intranuclear virus-like inclusions were found. The first type was papova virus-like structure with high electron density measured 30--35 nm in diameter. The second type was paramyxovirus-like structure with granulo-fibrilar shape. The third type was large hexogonal core with high electron density measured 100 nm in diameter. These intranuclear virus-like bodies were not specific in the present case; however, it was speculated that intranuclear virus-like inclusions might have a deep relation to change the function of the nuclei and produced large intraplasmic inclusion bodies."}
{"id": "PMID:216223", "title": "Choroid plexus papilloma: light and electron microscopic study of three cases.", "content": "Three cases of choroid plexus papilloma were studied by light and electron microscopy. All had the typical papillary pattern, and, in addition, two exhibited solid areas of tumor growth which predominated in one case. PAS positive (diastase resistant) and argyrophilic cytoplasmic inclusions were present in all three tumors but were particularly abundant in the predominantly solid one. Ultrastructurally, the inclusions appeared as irregularly shaped structures containing lipid droplets, filamentous material and microtubules, and resembled the \"silver bodies\" of Biondi found in normal choroid plexus. Along with other ultrastructural features of normal choroid plexus, these cytoplasmic inclusions may be helpful in the differential diagnosis of papillary tumors involving the ventricular system.", "contents": "Choroid plexus papilloma: light and electron microscopic study of three cases. Three cases of choroid plexus papilloma were studied by light and electron microscopy. All had the typical papillary pattern, and, in addition, two exhibited solid areas of tumor growth which predominated in one case. PAS positive (diastase resistant) and argyrophilic cytoplasmic inclusions were present in all three tumors but were particularly abundant in the predominantly solid one. Ultrastructurally, the inclusions appeared as irregularly shaped structures containing lipid droplets, filamentous material and microtubules, and resembled the \"silver bodies\" of Biondi found in normal choroid plexus. Along with other ultrastructural features of normal choroid plexus, these cytoplasmic inclusions may be helpful in the differential diagnosis of papillary tumors involving the ventricular system."}
{"id": "PMID:216224", "title": "Somatic unmyelinated fibre degeneration in rabbits with granulomatous hypersensitivity produced by a non-myelin antigen in sensory peripheral nerve.", "content": "Rabbits previously sensitised by injection of human sensory peripheral nerve showed degeneration of somatic unmyelinated fibres at skin test sites when challenged by sensory nerve or certain non-myelin fractions prepared from human sensory nerve. Epithelioid cells were found in the endoneurium and may mediate the nerve damage. The degeneration was consistently found and lasted for at least 58 days. Phagocytosing macrophages were absent. Differences in the pattern of nerve damage to that of EAN and EAE are discussed.", "contents": "Somatic unmyelinated fibre degeneration in rabbits with granulomatous hypersensitivity produced by a non-myelin antigen in sensory peripheral nerve. Rabbits previously sensitised by injection of human sensory peripheral nerve showed degeneration of somatic unmyelinated fibres at skin test sites when challenged by sensory nerve or certain non-myelin fractions prepared from human sensory nerve. Epithelioid cells were found in the endoneurium and may mediate the nerve damage. The degeneration was consistently found and lasted for at least 58 days. Phagocytosing macrophages were absent. Differences in the pattern of nerve damage to that of EAN and EAE are discussed."}
{"id": "PMID:216225", "title": "Wolman's disease: ultrastructural evidence of lipid accumulation in central and peripheral nervous systems.", "content": "We report the first case of Wolman's disease in which the fine structure of either the peripheral or the central nervous system has been examined. We confirm ultrastructurally the presence of lipid within endothelial and pericytic cells. Several cell types previously believed to be uninvolved in this storage process demonstrate lipid inclusions characteristic of Wolman's disease: perineural, endoneurial and Schwann cells of peripheral nerve, and oligodendrocytes and astrocytes of the central nervous system.", "contents": "Wolman's disease: ultrastructural evidence of lipid accumulation in central and peripheral nervous systems. We report the first case of Wolman's disease in which the fine structure of either the peripheral or the central nervous system has been examined. We confirm ultrastructurally the presence of lipid within endothelial and pericytic cells. Several cell types previously believed to be uninvolved in this storage process demonstrate lipid inclusions characteristic of Wolman's disease: perineural, endoneurial and Schwann cells of peripheral nerve, and oligodendrocytes and astrocytes of the central nervous system."}
{"id": "PMID:216226", "title": "[Peripheral nerve changes in Tangier disease. Comparative light-, electron-microscopic and cytometric studies (author's transl)].", "content": "A sural nerve biopsy was performed in a 55-year-old male patient with Tangier disease (familial-lipoprotein deficiency). Light-microscopy showed an increase in the endoneural connective tissue and a loss of nerve fibers indicating a chronic peripheral neuropathy. Electron-microscopy revealed an accumulation of lipid droplets within Schwann cells of myelinated and unmyelinated nerve fibers. When compared with age-matched controls the myelinated fiber density was reduced with a relative preponderance of small myelinated fibers. In addition, distributional cytometric studies of nerve fibers in relation to the perineurium and endoneurial capillaries showed: Contrary to 4.6-7.5 micron thick nerve fibers, which accumulated in the center of the nerve fascicle, small (0.5-4.5 micron) and large (7.6-10.0 micron) fibers lay nearby the perineurium. The measured increase in small myelinated nerve fibers around endoneurial capillaries may be explained as a sign of regeneration.", "contents": "[Peripheral nerve changes in Tangier disease. Comparative light-, electron-microscopic and cytometric studies (author's transl)]. A sural nerve biopsy was performed in a 55-year-old male patient with Tangier disease (familial-lipoprotein deficiency). Light-microscopy showed an increase in the endoneural connective tissue and a loss of nerve fibers indicating a chronic peripheral neuropathy. Electron-microscopy revealed an accumulation of lipid droplets within Schwann cells of myelinated and unmyelinated nerve fibers. When compared with age-matched controls the myelinated fiber density was reduced with a relative preponderance of small myelinated fibers. In addition, distributional cytometric studies of nerve fibers in relation to the perineurium and endoneurial capillaries showed: Contrary to 4.6-7.5 micron thick nerve fibers, which accumulated in the center of the nerve fascicle, small (0.5-4.5 micron) and large (7.6-10.0 micron) fibers lay nearby the perineurium. The measured increase in small myelinated nerve fibers around endoneurial capillaries may be explained as a sign of regeneration."}
{"id": "PMID:216227", "title": "Joint changes after overuse and peak overloading of rabbit knees in vivo.", "content": "The effect of overuse and overuse combined with axial peak overloading on the knee joints of living rabbits has been investigated. A specially constructed apparatus was used for this purpose. Physical and biochemical changes are reported and include: 1. Early and progressive damage to the articular cartilage surface shown by the scanning electron microscope. 2. The presence of an increased amount of prostaglandin E in the synovial fluid. 3. A reduction of cyclic 3'--5' monophosphate in the subchondral bone. 4. Late changes which were consistent with osteoarthritis. These changes were found only in the joints subjected to simultaneous overuse and peak overloading. The results suggest that: 1. Cartilage damage and chemical changes in the subchondral bone are simultaneous and are both responsible for eventual degenerative changes. 2. Frictional overuse alone does not seem to be responsible for the production of oesteoarthritis.", "contents": "Joint changes after overuse and peak overloading of rabbit knees in vivo. The effect of overuse and overuse combined with axial peak overloading on the knee joints of living rabbits has been investigated. A specially constructed apparatus was used for this purpose. Physical and biochemical changes are reported and include: 1. Early and progressive damage to the articular cartilage surface shown by the scanning electron microscope. 2. The presence of an increased amount of prostaglandin E in the synovial fluid. 3. A reduction of cyclic 3'--5' monophosphate in the subchondral bone. 4. Late changes which were consistent with osteoarthritis. These changes were found only in the joints subjected to simultaneous overuse and peak overloading. The results suggest that: 1. Cartilage damage and chemical changes in the subchondral bone are simultaneous and are both responsible for eventual degenerative changes. 2. Frictional overuse alone does not seem to be responsible for the production of oesteoarthritis."}
{"id": "PMID:216229", "title": "Liver cell dysplasia and hepatitis B surface and core antigens in cirrhosis and hepatocellular carcinoma of autopsy cases.", "content": "Liver tissues of 180 autopsy cases of cirrhosis and hepatoma and 285 consecutive autopsy cases of other diseases were studied for liver cell dysplasia correlated with hepatitis B surface and core antigens (HBsAg and HBcAg) in liver cells and sera, and antibody to HBsAg (anti-HBs) in sera. Liver cell dysplasia was characteristic in cirrhotic livers, particularly with hepatoma. No significant difference was found in age and sex between cirrhotic cases with and without dysplasia. Rate of positive HBsAg in liver cells and sera was significantly high in cirrhotic cases with dysplasia with or without hepatoma. Massive pattern distribution of orcein-positive liver cells was statistically significant in cirrhotic livers with or without hepatoma, but morphological characteristics of orcein-positive liver cells could not be correlated in significance with dysplasia and hepatoma. HBcAg showed neither correlation with liver cell dysplasia nor hepatoma. It appears to correlate with active cirrhosis, marked liver cell degeneration and necrosis, and membranous diffuse type HBsAg in liver cells.", "contents": "Liver cell dysplasia and hepatitis B surface and core antigens in cirrhosis and hepatocellular carcinoma of autopsy cases. Liver tissues of 180 autopsy cases of cirrhosis and hepatoma and 285 consecutive autopsy cases of other diseases were studied for liver cell dysplasia correlated with hepatitis B surface and core antigens (HBsAg and HBcAg) in liver cells and sera, and antibody to HBsAg (anti-HBs) in sera. Liver cell dysplasia was characteristic in cirrhotic livers, particularly with hepatoma. No significant difference was found in age and sex between cirrhotic cases with and without dysplasia. Rate of positive HBsAg in liver cells and sera was significantly high in cirrhotic cases with dysplasia with or without hepatoma. Massive pattern distribution of orcein-positive liver cells was statistically significant in cirrhotic livers with or without hepatoma, but morphological characteristics of orcein-positive liver cells could not be correlated in significance with dysplasia and hepatoma. HBcAg showed neither correlation with liver cell dysplasia nor hepatoma. It appears to correlate with active cirrhosis, marked liver cell degeneration and necrosis, and membranous diffuse type HBsAg in liver cells."}
{"id": "PMID:216231", "title": "Beta-adrenoceptors in the pregnant and non-pregnant myometrium of the goat and cow.", "content": "The muscle relaxing effect of beta-adrenoceptor agonists was examined without and with the presence of beta-adrenoceptor antagonists in strips from the pregnant and non-pregnant myometrium of the goat and from the pregnant myometrium of the cow. Isoprenaline, salbutamol and ritodrine caused a dose-dependent reduction of the spontaneous contractions of the pregnant myometrium and a dose-related and parallel shift to the right of the isoprenaline dose-response curve was obtained with butoxamine but not with practolol. Isoprenaline but neither salbutamol nor ritodrine caused a dose-related reduction of the spontaneous contractions in the non-pregnant myometrium and a dose-related and parallel shift to the right of the dose-response curve of isoprenaline was brought about with propranolol but not with either butoxamine or practolol. The muscle relaxing effect of ritodrine on the pregnant myometrium of the goat and cow shown in vitro was also demonstrated in vivo in the same species within eight hours of delivery. It is concluded that the beta-adrenoceptors in the pregnant myometrium of the goat and cow belong to the beta2-group whereas those in the non-pregnant myometrium cannot be classified as either beta1- or beta2-adrenoceptors.", "contents": "Beta-adrenoceptors in the pregnant and non-pregnant myometrium of the goat and cow. The muscle relaxing effect of beta-adrenoceptor agonists was examined without and with the presence of beta-adrenoceptor antagonists in strips from the pregnant and non-pregnant myometrium of the goat and from the pregnant myometrium of the cow. Isoprenaline, salbutamol and ritodrine caused a dose-dependent reduction of the spontaneous contractions of the pregnant myometrium and a dose-related and parallel shift to the right of the isoprenaline dose-response curve was obtained with butoxamine but not with practolol. Isoprenaline but neither salbutamol nor ritodrine caused a dose-related reduction of the spontaneous contractions in the non-pregnant myometrium and a dose-related and parallel shift to the right of the dose-response curve of isoprenaline was brought about with propranolol but not with either butoxamine or practolol. The muscle relaxing effect of ritodrine on the pregnant myometrium of the goat and cow shown in vitro was also demonstrated in vivo in the same species within eight hours of delivery. It is concluded that the beta-adrenoceptors in the pregnant myometrium of the goat and cow belong to the beta2-group whereas those in the non-pregnant myometrium cannot be classified as either beta1- or beta2-adrenoceptors."}
{"id": "PMID:216230", "title": "Ectopic ACTH-MSH producing carcinoid tumor with multiple endocrine hyperplasia in a child.", "content": "An autopsy case of a 9-year-old Japanese girl revealed a carcinoid tumor originating in the duodenum and hyperplasia of the multiple endocrine organs as manifested by ectopic ACTH syndrome, carcinoid syndrome and giantism. The tumor cells were positive for histochemical argyrophile reaction and two types of secretory granules were identified by electron microscopy. Biochemical assay revealed the production of ACTH and beta-MSH by the tumor cells. Other changes of multiple endocrine organs included acidophil dominant hyperplasia of the pituitary, diffuse hyperplasia of the thyroid, chief cell hyperplasia of the parathyroid, hyperplasia of the islets of Langerhans and the adrenal cortex. This case was considered to be a type of multiple endocrine adenomatosis including carcinoid tumor. The relationship between the carcinoid tumor and multiple endocrine adenomatosis was discussed.", "contents": "Ectopic ACTH-MSH producing carcinoid tumor with multiple endocrine hyperplasia in a child. An autopsy case of a 9-year-old Japanese girl revealed a carcinoid tumor originating in the duodenum and hyperplasia of the multiple endocrine organs as manifested by ectopic ACTH syndrome, carcinoid syndrome and giantism. The tumor cells were positive for histochemical argyrophile reaction and two types of secretory granules were identified by electron microscopy. Biochemical assay revealed the production of ACTH and beta-MSH by the tumor cells. Other changes of multiple endocrine organs included acidophil dominant hyperplasia of the pituitary, diffuse hyperplasia of the thyroid, chief cell hyperplasia of the parathyroid, hyperplasia of the islets of Langerhans and the adrenal cortex. This case was considered to be a type of multiple endocrine adenomatosis including carcinoid tumor. The relationship between the carcinoid tumor and multiple endocrine adenomatosis was discussed."}
{"id": "PMID:216232", "title": "Decorporation of copper from liver subcellular fractions after alimentary loading of rats.", "content": "Subcellular copper distribution was studied after single alimentary loading of rats with copper sulfate and after 2- and 4-day spontaneous decorporation of the metal. Copper content in mitochondria and in the soluble fraction was found to rise as early as the 1st day. Then it decreased reaching the normal values after 2-day and 4-day autodecorporation for cytosol and mitochondria, respectively. The activities of rotenone-sensitive NADH-cytochrome c reductase, succinate-cytochrome c reductase and cytochrome oxidase were inhibited by copper treatment but after a 4-day decorporation they became normal. On the contrary, rotenone-insensitive NADH-cytochrome c reductase was activated. Single alimentary copper treatment induced changes in electron transport and oxidative phosphorylation with succinate and glutamate as substrates. The changes established were in accordance with the decreased enzyme activities. After chronic copper loading (7-8 weeks) the interruption of copper-enriched diet for 5 days led to restoration of the copper content in the subcellular fractions. Treatment with unitiol did not change the spontaneous decorporation.", "contents": "Decorporation of copper from liver subcellular fractions after alimentary loading of rats. Subcellular copper distribution was studied after single alimentary loading of rats with copper sulfate and after 2- and 4-day spontaneous decorporation of the metal. Copper content in mitochondria and in the soluble fraction was found to rise as early as the 1st day. Then it decreased reaching the normal values after 2-day and 4-day autodecorporation for cytosol and mitochondria, respectively. The activities of rotenone-sensitive NADH-cytochrome c reductase, succinate-cytochrome c reductase and cytochrome oxidase were inhibited by copper treatment but after a 4-day decorporation they became normal. On the contrary, rotenone-insensitive NADH-cytochrome c reductase was activated. Single alimentary copper treatment induced changes in electron transport and oxidative phosphorylation with succinate and glutamate as substrates. The changes established were in accordance with the decreased enzyme activities. After chronic copper loading (7-8 weeks) the interruption of copper-enriched diet for 5 days led to restoration of the copper content in the subcellular fractions. Treatment with unitiol did not change the spontaneous decorporation."}
{"id": "PMID:216228", "title": "Bell's palsy-beneficial effect of treatment with adrenocorticotrophic hormone (ACTH) in patients with a poor prognosis.", "content": "In 111 patients with idiopathic peripheral facial paralysis (Bell's palsy) the prognosis was established during the first days of the disease, using sialometry and the stapedius reflex test in 102 patients. A poor prognosis was indicated in 36 patients. Treatment with adrenocorticotrophic hormone (ACTH) was commenced within 10 days (in the majority within 5 days) of the onset of the paresis in 31 of those patients with a poor prognosis. The recovery rate in the ACTH-treated group was superior compared with the untreated control group of patients with a poor prognosis. The difference is statistically significant. Those patients with a good prognosis were not treated but merely followed up. Some factors which could influence the result of the treatment are considered.", "contents": "Bell's palsy-beneficial effect of treatment with adrenocorticotrophic hormone (ACTH) in patients with a poor prognosis. In 111 patients with idiopathic peripheral facial paralysis (Bell's palsy) the prognosis was established during the first days of the disease, using sialometry and the stapedius reflex test in 102 patients. A poor prognosis was indicated in 36 patients. Treatment with adrenocorticotrophic hormone (ACTH) was commenced within 10 days (in the majority within 5 days) of the onset of the paresis in 31 of those patients with a poor prognosis. The recovery rate in the ACTH-treated group was superior compared with the untreated control group of patients with a poor prognosis. The difference is statistically significant. Those patients with a good prognosis were not treated but merely followed up. Some factors which could influence the result of the treatment are considered."}
{"id": "PMID:216233", "title": "The effect of exhaustive swimming and chloramphenicol on the content of mitochondrial protein and cytochromes in rat liver and myocardium.", "content": "The content of mitochondrial protein and cytochromes aa3, b, c1 and c in rat liver and heart was determined in four groups of rats: controls, CAP-treated rats, exercised rats and CAP-treated exercised rats. Single swimming does not change the amount of mitochondrial protein in liver and myocardium as well as the content of cytochromes aa3, b, c1 and c in liver mitochondria. The content of cyt. c is lowered in heart mitochondria. CAP treatment of rats for three days decreases the amount of mitochondrial proteins and cyt. aa3, and b whereas no such changes are observed in heart mitochondria. The subsequent swimming on the background of the inhibitor does not affect additionally liver mitochondria, but lowers significantly the mitochondrial protein and the content of cyt. aa3, b, c1 and c in the myocardium. These data show that exhaustive muscular work alters the effect of CAP in heart mitochondria. Three hours of exhaustive swimming are not sufficient to change neither the amount of total mitochondrial protein, nor the cytochrome content. The lowered cyt. c content in heart mitochondria after swimming is explained by an intensified permeability of the outer membrane. Thus, the changes in the activity of some enzymes and the oxidative phosphorylation previously reported by us, are not due to alterations in the protein synthesis.", "contents": "The effect of exhaustive swimming and chloramphenicol on the content of mitochondrial protein and cytochromes in rat liver and myocardium. The content of mitochondrial protein and cytochromes aa3, b, c1 and c in rat liver and heart was determined in four groups of rats: controls, CAP-treated rats, exercised rats and CAP-treated exercised rats. Single swimming does not change the amount of mitochondrial protein in liver and myocardium as well as the content of cytochromes aa3, b, c1 and c in liver mitochondria. The content of cyt. c is lowered in heart mitochondria. CAP treatment of rats for three days decreases the amount of mitochondrial proteins and cyt. aa3, and b whereas no such changes are observed in heart mitochondria. The subsequent swimming on the background of the inhibitor does not affect additionally liver mitochondria, but lowers significantly the mitochondrial protein and the content of cyt. aa3, b, c1 and c in the myocardium. These data show that exhaustive muscular work alters the effect of CAP in heart mitochondria. Three hours of exhaustive swimming are not sufficient to change neither the amount of total mitochondrial protein, nor the cytochrome content. The lowered cyt. c content in heart mitochondria after swimming is explained by an intensified permeability of the outer membrane. Thus, the changes in the activity of some enzymes and the oxidative phosphorylation previously reported by us, are not due to alterations in the protein synthesis."}
{"id": "PMID:216234", "title": "Mechanism of action of benzodiazepines - the GABA hypothesis.", "content": "Benzodiazepines influence on a number of neurotransmitters such as acetylcholine, catecholamines, serotonin, glycine and gamma-aminobutyric acid (GABA), but during recent years the major interest has been focused on the inhibitory transmitter GABA. This paper reviews the hypothesis that benzodiazepines act via GABA-ergic mechanisms in the central nervous system. At NIMH in Washington D.C. a novel method to measure the turnover rate of GABA in rat brain nuclei has been developed (Bertilsson et al., J. Pharmacol. Exp. Therap. 200: 277, 1977). The incorporation of 13C from glucose into glutamic acid and GABA was quantitated in stereomicroscopically isolated nuclei. Using this technique it was shown that the GABA agonist muscimol and diazepam have a similar action. Both drugs decreased the turnover rate of GABA in N. caudatus and accumbens, but not in globus pallidus (Mao et al., Biol. Psychiatry 12: 395, 1977). This gives further support to the theory that diazepam acts as a GABA-mimetic drug.", "contents": "Mechanism of action of benzodiazepines - the GABA hypothesis. Benzodiazepines influence on a number of neurotransmitters such as acetylcholine, catecholamines, serotonin, glycine and gamma-aminobutyric acid (GABA), but during recent years the major interest has been focused on the inhibitory transmitter GABA. This paper reviews the hypothesis that benzodiazepines act via GABA-ergic mechanisms in the central nervous system. At NIMH in Washington D.C. a novel method to measure the turnover rate of GABA in rat brain nuclei has been developed (Bertilsson et al., J. Pharmacol. Exp. Therap. 200: 277, 1977). The incorporation of 13C from glucose into glutamic acid and GABA was quantitated in stereomicroscopically isolated nuclei. Using this technique it was shown that the GABA agonist muscimol and diazepam have a similar action. Both drugs decreased the turnover rate of GABA in N. caudatus and accumbens, but not in globus pallidus (Mao et al., Biol. Psychiatry 12: 395, 1977). This gives further support to the theory that diazepam acts as a GABA-mimetic drug."}
{"id": "PMID:216235", "title": "The effect of oxazepam on sleep in normal human volunteers.", "content": "The effects of 25 mg of oxazepam, a benzodiazepine with a short half-life and no active metabolites, were compared with placebo in two healthy volunteers in a single-blind polygraphically recorded sleep study. The experiment lasted for 24 nights and recordings were made for 11 nights. It was found that 25 mg oxazepam induced sleep faster than placebo, and that the subjects awoke less often during the treatment period. The total amount of REM-sleep was not affected. However, REM-sleep was shortened during the first part of the night and extended during the latter part of the night. Slow-wave sleep diminished differently in the two subjects, possibly due to interindividual differences in the rate of elimination of oxazepam. The effect on blood pressure was small, and the normal physiological difference between bedtime and morning blood pressure was preserved.", "contents": "The effect of oxazepam on sleep in normal human volunteers. The effects of 25 mg of oxazepam, a benzodiazepine with a short half-life and no active metabolites, were compared with placebo in two healthy volunteers in a single-blind polygraphically recorded sleep study. The experiment lasted for 24 nights and recordings were made for 11 nights. It was found that 25 mg oxazepam induced sleep faster than placebo, and that the subjects awoke less often during the treatment period. The total amount of REM-sleep was not affected. However, REM-sleep was shortened during the first part of the night and extended during the latter part of the night. Slow-wave sleep diminished differently in the two subjects, possibly due to interindividual differences in the rate of elimination of oxazepam. The effect on blood pressure was small, and the normal physiological difference between bedtime and morning blood pressure was preserved."}
{"id": "PMID:216236", "title": "Stereotactic computer tomography for biopsy of gliomas.", "content": "A technique is introduced enabling automatic transfer of coordinates obtained at computer tomography into a stereotactic system previously applied in biopsies of brain lesions. Four to five biopsies from different parts of gliomas were taken to compare the structures demonstrated on computer tomography with the microscopic appearances. Of 45 biopsies in 13 patients, 36 were predicted correctly. This also served as an attempt to classify gliomas on the basis of their appearance in the CT image.", "contents": "Stereotactic computer tomography for biopsy of gliomas. A technique is introduced enabling automatic transfer of coordinates obtained at computer tomography into a stereotactic system previously applied in biopsies of brain lesions. Four to five biopsies from different parts of gliomas were taken to compare the structures demonstrated on computer tomography with the microscopic appearances. Of 45 biopsies in 13 patients, 36 were predicted correctly. This also served as an attempt to classify gliomas on the basis of their appearance in the CT image."}
{"id": "PMID:216237", "title": "En-bloc irradiation of unresectable bronchogenic carcinomas and their regional lymphatics.", "content": "Patients with unresectable or inoperable bronchial carcinoma were treated with en-bloc irradiation of the tumour and the mediastinal lymph nodes to a total target absorbed dose of 40 Gy in 20 fractions. The first 52 patients were treated in one series and the last 45 patients in two series (split-course). Radiation adverse effects were only mild. The two regimens gave the same palliative results. The median survival was the same for the 2 groups (8 months). Most patients died in disseminated disease.", "contents": "En-bloc irradiation of unresectable bronchogenic carcinomas and their regional lymphatics. Patients with unresectable or inoperable bronchial carcinoma were treated with en-bloc irradiation of the tumour and the mediastinal lymph nodes to a total target absorbed dose of 40 Gy in 20 fractions. The first 52 patients were treated in one series and the last 45 patients in two series (split-course). Radiation adverse effects were only mild. The two regimens gave the same palliative results. The median survival was the same for the 2 groups (8 months). Most patients died in disseminated disease."}
{"id": "PMID:216238", "title": "Postoperative irradiation of glioblastomas. Results in a randomized series.", "content": "A material of 108 patients with glioblastoma is presented. The series was randomized in two groups: cases only operated upon and cases with postoperative irradiation in addition. Patients dead within 2 months after operation were excluded in estimating the real value of the postoperative irradiation. The irradiated cases had a 6-month survival rate of 64 per cent and a one-year survival rate of 19 per cent; the non-irradiated cases a 6-month survival rate of 28 per cent and a one-year survival rate of 0 per cent.", "contents": "Postoperative irradiation of glioblastomas. Results in a randomized series. A material of 108 patients with glioblastoma is presented. The series was randomized in two groups: cases only operated upon and cases with postoperative irradiation in addition. Patients dead within 2 months after operation were excluded in estimating the real value of the postoperative irradiation. The irradiated cases had a 6-month survival rate of 64 per cent and a one-year survival rate of 19 per cent; the non-irradiated cases a 6-month survival rate of 28 per cent and a one-year survival rate of 0 per cent."}
{"id": "PMID:216239", "title": "Combination chemotherapy in the management of superior vena caval obstruction in small-cell anaplastic carcinoma of the lung.", "content": "Among 225 consecutive patients with small-cell anaplastic bronchogenic carcinoma, 26 (11.5%) had superior vena caval obstruction when the malignancy was diagnosed. Of these 26 patients, a consecutive series of 22 were treated initially with combination chemotherapy (cyclophosphamide, methotrexate and CCNU, in some cases combined with vincristine) alone, and in all these cases resolution of the syndrome was prompt within a median of 7 days. In no case were symptoms increased transiently by the treatment. No difference in response rate was observed between the histologic subtypes of small-cell anaplastic bronchogenic carcinoma according to the WHO classification. Combination chemotherapy alone is an effective treatment of superior vena caval obstruction in patients with small-cell anaplastic bronchogenic carcinoma.", "contents": "Combination chemotherapy in the management of superior vena caval obstruction in small-cell anaplastic carcinoma of the lung. Among 225 consecutive patients with small-cell anaplastic bronchogenic carcinoma, 26 (11.5%) had superior vena caval obstruction when the malignancy was diagnosed. Of these 26 patients, a consecutive series of 22 were treated initially with combination chemotherapy (cyclophosphamide, methotrexate and CCNU, in some cases combined with vincristine) alone, and in all these cases resolution of the syndrome was prompt within a median of 7 days. In no case were symptoms increased transiently by the treatment. No difference in response rate was observed between the histologic subtypes of small-cell anaplastic bronchogenic carcinoma according to the WHO classification. Combination chemotherapy alone is an effective treatment of superior vena caval obstruction in patients with small-cell anaplastic bronchogenic carcinoma."}
{"id": "PMID:216240", "title": "Elevation of high-density lipoprotein in epileptic patients treated with phenytoin.", "content": "Previous observations have shown that serum alpha (high-density) lipoprotein (HDL) cholesterol is increased by some agents which also act as liver microsomal inducers. Against this background we measured the serum HDL and other lipoprotein and apolipoprotein A levels in 28 epileptic patients who received phenytoin as the only medication. In comparison with healthy controls of similar age and sex, the phenytoin users had significantly higher HDL cholesterol (p less than 0.001) and apolipoprotein A-I (p less than 0.01) levels. Highest values of both parameters were found in patients whose serum phenytoin concentration was within the therapeutic range. HDL cholesterol levels were above the control mean +2 S.D. in 43% of the phenytoin users. Hypertriglyceridemia was more common among male phenytoin users than in control males (33 vs. 16%). It is suggested that phenytoin increases the secretion of nascent HDL particles (and probably also that of VLDL) by the liver and that this could be associated with the induction of hepatic microsomes. Since HDL is inversely reversely related to risk of coronary heart disease, the observed increase of this lipoprotein may be an example of a beneficial side-effect of a drug.", "contents": "Elevation of high-density lipoprotein in epileptic patients treated with phenytoin. Previous observations have shown that serum alpha (high-density) lipoprotein (HDL) cholesterol is increased by some agents which also act as liver microsomal inducers. Against this background we measured the serum HDL and other lipoprotein and apolipoprotein A levels in 28 epileptic patients who received phenytoin as the only medication. In comparison with healthy controls of similar age and sex, the phenytoin users had significantly higher HDL cholesterol (p less than 0.001) and apolipoprotein A-I (p less than 0.01) levels. Highest values of both parameters were found in patients whose serum phenytoin concentration was within the therapeutic range. HDL cholesterol levels were above the control mean +2 S.D. in 43% of the phenytoin users. Hypertriglyceridemia was more common among male phenytoin users than in control males (33 vs. 16%). It is suggested that phenytoin increases the secretion of nascent HDL particles (and probably also that of VLDL) by the liver and that this could be associated with the induction of hepatic microsomes. Since HDL is inversely reversely related to risk of coronary heart disease, the observed increase of this lipoprotein may be an example of a beneficial side-effect of a drug."}
{"id": "PMID:216255", "title": "Air pollution exposures to five target health hazards.", "content": "The Occupational Safety and Health Administration (OSHA) initiated a Target Health Hazards Program (THHP) in January 1972. The five substances singled out as target health hazards (asbestos, cotton dust, carbon monoxide, lead and silica) are discussed. Outlines are given of the pertinent points of the present and proposed OSHA standards for each substance as well as data of OSHA inspection efforts with regard to the THHP. A summary statement is made of the National Emphasis Program and of OSHA efforts to upgrade standard setting and compliance activities.", "contents": "Air pollution exposures to five target health hazards. The Occupational Safety and Health Administration (OSHA) initiated a Target Health Hazards Program (THHP) in January 1972. The five substances singled out as target health hazards (asbestos, cotton dust, carbon monoxide, lead and silica) are discussed. Outlines are given of the pertinent points of the present and proposed OSHA standards for each substance as well as data of OSHA inspection efforts with regard to the THHP. A summary statement is made of the National Emphasis Program and of OSHA efforts to upgrade standard setting and compliance activities."}
{"id": "PMID:216256", "title": "Regression of the larval opisthonephros during metamorphosis of the sea lamprey, Petromyzon marinus L.", "content": "The opisthonephric kidney of larval anadromous sea lamprey, Petromyzon marinus L., undergoes a programmed regression during metamorphosis. Degeneration is initiated in the anterior end of each kidney and progresses posteriorly until the kidneys are reduced to short, pigmented strands by the end of metamorphosis. The first sign of degeneration in both the epithelium of the renal corpuscles and the tubules is a folding of the basal lamina. Autolysis then occurs throughout the entire epithelium of the nephron with the gradual accumulation of larger and greater numbers of acid phosphatase-containing autophagic vacuoles, cytosomes, and myelin figures. Cytoplasmic debris and electron-dense material accumulates in the tubular lumina and in the urinary space. Although no definitive evidence is provided for the method of removal of the tubular epithelium, macrophages play a large part in the phagocytosis of the components of the renal corpuscle. Mesangial cells appear to engulf debris from the capillaries while a second type of macrophage is involved in the destruction of podocytes and parietal epithelial cells. The method of programmed degeneration of the renal corpuscle closely resembles descriptions of the mammalian renal corpuscle in diseased conditions. The sole surviving element of the degeneration of the entire nephron epithelium is a pleated basal lamina. The regressing larval opisthonephros has potential as an alternative system for studying a normal developmental pattern such as tissue regression.", "contents": "Regression of the larval opisthonephros during metamorphosis of the sea lamprey, Petromyzon marinus L. The opisthonephric kidney of larval anadromous sea lamprey, Petromyzon marinus L., undergoes a programmed regression during metamorphosis. Degeneration is initiated in the anterior end of each kidney and progresses posteriorly until the kidneys are reduced to short, pigmented strands by the end of metamorphosis. The first sign of degeneration in both the epithelium of the renal corpuscles and the tubules is a folding of the basal lamina. Autolysis then occurs throughout the entire epithelium of the nephron with the gradual accumulation of larger and greater numbers of acid phosphatase-containing autophagic vacuoles, cytosomes, and myelin figures. Cytoplasmic debris and electron-dense material accumulates in the tubular lumina and in the urinary space. Although no definitive evidence is provided for the method of removal of the tubular epithelium, macrophages play a large part in the phagocytosis of the components of the renal corpuscle. Mesangial cells appear to engulf debris from the capillaries while a second type of macrophage is involved in the destruction of podocytes and parietal epithelial cells. The method of programmed degeneration of the renal corpuscle closely resembles descriptions of the mammalian renal corpuscle in diseased conditions. The sole surviving element of the degeneration of the entire nephron epithelium is a pleated basal lamina. The regressing larval opisthonephros has potential as an alternative system for studying a normal developmental pattern such as tissue regression."}
{"id": "PMID:216258", "title": "Immunoreactive beta-endorphin and ACTH in the same neurons of the hypothalamic arcuate nucleus in the rat.", "content": "Immunoreactive ACTH and beta-endorphin (beta-End) were localized in the brain and pituitaries of normal and colchicine-treated rats, using the immunoperoxidase method at the light microscopic level. On adjacent serial 5-micron paraffin sections of anterior pituitaries, both ACTH and beta-End could be found in the same cells. On adjacent 5-micron paraffin sections of brains of colchicine-treated rats, both ACTH and beta-End could be found in the same perikarya of hypothalamic arcuate nucleus neurons. It appeared that all perikarya containing beta-End contained ACTH as well, suggesting that neurons producing beta-End also produce ACTH. Pathways of ACTH fibers corresponded to pathways of beta-End fibers. These findings suggest that the synthesis, and transport, of ACTH and beta-End are linked in the brain as well as in the pituitary, possibly through a common precursor.", "contents": "Immunoreactive beta-endorphin and ACTH in the same neurons of the hypothalamic arcuate nucleus in the rat. Immunoreactive ACTH and beta-endorphin (beta-End) were localized in the brain and pituitaries of normal and colchicine-treated rats, using the immunoperoxidase method at the light microscopic level. On adjacent serial 5-micron paraffin sections of anterior pituitaries, both ACTH and beta-End could be found in the same cells. On adjacent 5-micron paraffin sections of brains of colchicine-treated rats, both ACTH and beta-End could be found in the same perikarya of hypothalamic arcuate nucleus neurons. It appeared that all perikarya containing beta-End contained ACTH as well, suggesting that neurons producing beta-End also produce ACTH. Pathways of ACTH fibers corresponded to pathways of beta-End fibers. These findings suggest that the synthesis, and transport, of ACTH and beta-End are linked in the brain as well as in the pituitary, possibly through a common precursor."}
{"id": "PMID:216259", "title": "Dietary fiber and blood lipids: reduction of serum cholesterol in type II hyperlipidemia by guar gum.", "content": "Guar gum, a storage polysaccharide galactomannan and a form of dietary fiber, was administered to 10 patients with type II a or b hyperlipidemia for 2 weeks. Five grams of gum was given before each of three meals daily, either in a specially prepared soup or mixed with fruit juice or milk. No other deliberate change of diet was made. Three patients had been taking 12 to 16 g/day of cholestyramine for more than 2 years and one had been taking 1000 mg of clofibrate daily. These drugs were continued throughout the trial. Serum cholesterol levels of all 10 patients had been stable for 6 to 18 months before the trial at the start of which the mean level was 345 +/- 15 mg/dl. After 2 weeks of guar gum the mean was 308 +/- 16 mg/dl, a fall of 10.6% (P less than 0.01). Serum triglyceride was not changed significantly. Guar gum, which can be incorporated into foods, merits further study as a potential hypocholesterolemic agent.", "contents": "Dietary fiber and blood lipids: reduction of serum cholesterol in type II hyperlipidemia by guar gum. Guar gum, a storage polysaccharide galactomannan and a form of dietary fiber, was administered to 10 patients with type II a or b hyperlipidemia for 2 weeks. Five grams of gum was given before each of three meals daily, either in a specially prepared soup or mixed with fruit juice or milk. No other deliberate change of diet was made. Three patients had been taking 12 to 16 g/day of cholestyramine for more than 2 years and one had been taking 1000 mg of clofibrate daily. These drugs were continued throughout the trial. Serum cholesterol levels of all 10 patients had been stable for 6 to 18 months before the trial at the start of which the mean level was 345 +/- 15 mg/dl. After 2 weeks of guar gum the mean was 308 +/- 16 mg/dl, a fall of 10.6% (P less than 0.01). Serum triglyceride was not changed significantly. Guar gum, which can be incorporated into foods, merits further study as a potential hypocholesterolemic agent."}
{"id": "PMID:216260", "title": "The molecular mode of action of Clostridium perfringens enterotoxin.", "content": "While certain strains of Clostridium perfringens have been associated with food poisoning outbreaks for the past 30 years, it has been only during the past 10 years that progress has been made in describing the disease process. And only within the past 5 years has meaningful progress been made in understanding the mechanism by which the disease is caused. Early observations, that the protein enterotoxin can cause erythema, increase capillary permeability, and exhibit parasympathomimetic properties, have been greatly added to in more recent studies. It is now believed tht the enterotoxin can alter intestinal transport of fluid, ions, and glucose, cause tissue damage in the gut and inhibit metabolic processes in intestinal tissue. Furthermore, the enterotoxin is thought to act very quickly (in a matter of minutes, compared to hours for other known enteropathogenic factors) and to affect basic function (macromolecular synthesis) and structure (membrane damage to microvillus brush borders) of individual cells. These findings have opened up many new questions that hopefully, when answered, will further the understanding of how this enterotoxin acts, as well as other enterotoxins being studied today.", "contents": "The molecular mode of action of Clostridium perfringens enterotoxin. While certain strains of Clostridium perfringens have been associated with food poisoning outbreaks for the past 30 years, it has been only during the past 10 years that progress has been made in describing the disease process. And only within the past 5 years has meaningful progress been made in understanding the mechanism by which the disease is caused. Early observations, that the protein enterotoxin can cause erythema, increase capillary permeability, and exhibit parasympathomimetic properties, have been greatly added to in more recent studies. It is now believed tht the enterotoxin can alter intestinal transport of fluid, ions, and glucose, cause tissue damage in the gut and inhibit metabolic processes in intestinal tissue. Furthermore, the enterotoxin is thought to act very quickly (in a matter of minutes, compared to hours for other known enteropathogenic factors) and to affect basic function (macromolecular synthesis) and structure (membrane damage to microvillus brush borders) of individual cells. These findings have opened up many new questions that hopefully, when answered, will further the understanding of how this enterotoxin acts, as well as other enterotoxins being studied today."}
{"id": "PMID:216261", "title": "Nutrition imbalance and angiotoxins as dietary risk factors in coronary heart disease.", "content": "Imbalancing nutritionally adequate diets with an excessive amount of fat calories and cholesterol has obscured the fact that intimal thickening occurs spontaneously in time on low-fat cholesterol-free diets during the aging process, and that intimal thickening can be accelerated by dietary angiotoxic \"risk factors.\" Electron microscopy of arterial tissue from animal models identified degenerated smooth muscle cells in the fetus from sows kept on low-fat cholesterol-free diets. After birth, the degenerated smooth muscle cells increased in number with age. The presence of angiotoxic \"risk factors\" such as oxidized cholesterol and vitamin D3 (cholecalciferol) in the diet of such animal models increased the frequency of smooth muscle cell death in their arteries. Two types of pathology could be developed in the thoracic aorta by continuous or short term feeding of 12.5 times more vitamin D than normally present in commercial rations: 1) a diffuse fibroelastic intimal thickening in the thoracic aorta (arteriosclerosis) with no evidence of lipid deposition by continuous feeding of vitamin D or 2) an initimal thickening in the thoracic aorta and intimal thickening with foam cells and extracellular lipid deposits (atherosclerosis) in the coronary arteries after a short period of supplemental vitamin D followed by 3 to 4 months of supplement-free diets. These two types of arterial damage were identical to that in the plugs of thoracic aorta obtained as a by-product of elective coronary bypass surgery. Although all of the possible sources of oxidized cholesterol in the diet have as yet not been identified, laboratory studies have identified oxidized cholesterol as an angiotoxic factor. Since population groups that consume less vitamin D-supplemented foods, less deep fat fried cholesterol-containing foods, and less hydrogenated fats have a lower incidence of coronary heart disease than Americans, it seems judicious for food processors to reduce these previously unconsidered risk factors to a minimum. This could be done by eliminating vitamin D2 and D3 from all vitamin supplements, from all food and cereal products and from the diet of livestock 1 month before they were killed so that the intake of vitamin D is no larger than the 400 IU/quart in milk which is necessary to prevent rickets in children. Deep fat fryers, which are kept at almost 200 C for 24 hr/day, could perhaps be replaced with microwave ovens in fast food chain outlets. Processors could hydrogenate vegetable oils to a minimum trans fatty acid content and rearrange this fat with polyunsaturated fats to produce high polyunsaturated fats trans-free margarines and shortenings.", "contents": "Nutrition imbalance and angiotoxins as dietary risk factors in coronary heart disease. Imbalancing nutritionally adequate diets with an excessive amount of fat calories and cholesterol has obscured the fact that intimal thickening occurs spontaneously in time on low-fat cholesterol-free diets during the aging process, and that intimal thickening can be accelerated by dietary angiotoxic \"risk factors.\" Electron microscopy of arterial tissue from animal models identified degenerated smooth muscle cells in the fetus from sows kept on low-fat cholesterol-free diets. After birth, the degenerated smooth muscle cells increased in number with age. The presence of angiotoxic \"risk factors\" such as oxidized cholesterol and vitamin D3 (cholecalciferol) in the diet of such animal models increased the frequency of smooth muscle cell death in their arteries. Two types of pathology could be developed in the thoracic aorta by continuous or short term feeding of 12.5 times more vitamin D than normally present in commercial rations: 1) a diffuse fibroelastic intimal thickening in the thoracic aorta (arteriosclerosis) with no evidence of lipid deposition by continuous feeding of vitamin D or 2) an initimal thickening in the thoracic aorta and intimal thickening with foam cells and extracellular lipid deposits (atherosclerosis) in the coronary arteries after a short period of supplemental vitamin D followed by 3 to 4 months of supplement-free diets. These two types of arterial damage were identical to that in the plugs of thoracic aorta obtained as a by-product of elective coronary bypass surgery. Although all of the possible sources of oxidized cholesterol in the diet have as yet not been identified, laboratory studies have identified oxidized cholesterol as an angiotoxic factor. Since population groups that consume less vitamin D-supplemented foods, less deep fat fried cholesterol-containing foods, and less hydrogenated fats have a lower incidence of coronary heart disease than Americans, it seems judicious for food processors to reduce these previously unconsidered risk factors to a minimum. This could be done by eliminating vitamin D2 and D3 from all vitamin supplements, from all food and cereal products and from the diet of livestock 1 month before they were killed so that the intake of vitamin D is no larger than the 400 IU/quart in milk which is necessary to prevent rickets in children. Deep fat fryers, which are kept at almost 200 C for 24 hr/day, could perhaps be replaced with microwave ovens in fast food chain outlets. Processors could hydrogenate vegetable oils to a minimum trans fatty acid content and rearrange this fat with polyunsaturated fats to produce high polyunsaturated fats trans-free margarines and shortenings."}
{"id": "PMID:216263", "title": "Relation of serum lipids and lipoproteins to obesity and sexual maturity in white and black children.", "content": "The interrelationships of serum lipids and lipoproteins with measures of body habitus and maturation stages were analyzed in a biracial population of 3151 children, ages 5--14 years. In general, triglycerides, pre-beta-lipoprotein, and beta-lipoprotein were positively correlated with body habitus and maturation while alpha-lipoprotein was negatively correlated. The relationships in most instances were more apparent in whites than in blacks, with the highest correlations observed in white boys. No significant correlations were observed between serum cholesterol and the anthropometric variables except in white boys. The most obese children tended to have higher levels of triglycerides, pre-beta-lipoprotein, and beta-lipoprotein, and lower levels of alpha-lipoprotein than the remaining population. In the total population, the multiple correlation coefficients with the children's age, race, sex weight-height index, triceps skinfold and maturation stage as the independent variables and the concentrations of the different serum variables as the dependent variables ranged from 0.04 to 0.11.", "contents": "Relation of serum lipids and lipoproteins to obesity and sexual maturity in white and black children. The interrelationships of serum lipids and lipoproteins with measures of body habitus and maturation stages were analyzed in a biracial population of 3151 children, ages 5--14 years. In general, triglycerides, pre-beta-lipoprotein, and beta-lipoprotein were positively correlated with body habitus and maturation while alpha-lipoprotein was negatively correlated. The relationships in most instances were more apparent in whites than in blacks, with the highest correlations observed in white boys. No significant correlations were observed between serum cholesterol and the anthropometric variables except in white boys. The most obese children tended to have higher levels of triglycerides, pre-beta-lipoprotein, and beta-lipoprotein, and lower levels of alpha-lipoprotein than the remaining population. In the total population, the multiple correlation coefficients with the children's age, race, sex weight-height index, triceps skinfold and maturation stage as the independent variables and the concentrations of the different serum variables as the dependent variables ranged from 0.04 to 0.11."}
{"id": "PMID:216264", "title": "Treatment of genital herpes simplex virus infection with photodynamic inactivation.", "content": "A double-blind randomized study to evaluate the effect of proflavine in the treatment of genital herpesvirus infection was conducted. One hundred fifty-seven women were studied, of whom 75 were treated with proflavine (treated women) and 82 were treated with placebo (control group). There were 62 women with primary disease and 95 with recurrent infection. Under the conditions by which this study was conducted, there was no apparent difference in the time of healing of lesions, development of recurrences, or virus isolation following treatment in the proflavine-treated and control groups.", "contents": "Treatment of genital herpes simplex virus infection with photodynamic inactivation. A double-blind randomized study to evaluate the effect of proflavine in the treatment of genital herpesvirus infection was conducted. One hundred fifty-seven women were studied, of whom 75 were treated with proflavine (treated women) and 82 were treated with placebo (control group). There were 62 women with primary disease and 95 with recurrent infection. Under the conditions by which this study was conducted, there was no apparent difference in the time of healing of lesions, development of recurrences, or virus isolation following treatment in the proflavine-treated and control groups."}
{"id": "PMID:216265", "title": "Retinal aneurysms in adult cytomegalovirus retinitis.", "content": "We observed aneurysms of the retinal arteries, capillaries, and venules occurring in a patient with cytomegalovirus retinitis. These aneurysms were caused by involvement of the retinal vascular endothelium resulting in focal weaknesses in the vascular walls. The clinical appearance of this retinitis superficially resembled retinal branch vein occlusion.", "contents": "Retinal aneurysms in adult cytomegalovirus retinitis. We observed aneurysms of the retinal arteries, capillaries, and venules occurring in a patient with cytomegalovirus retinitis. These aneurysms were caused by involvement of the retinal vascular endothelium resulting in focal weaknesses in the vascular walls. The clinical appearance of this retinitis superficially resembled retinal branch vein occlusion."}
{"id": "PMID:216266", "title": "A myofibroblastic tumor. Infantile digital fibroma (recurrent digital fibrous tumor of childhood).", "content": "Infantile digital fibromas are distinctive tumors both clinically and morphologically. A unique light microscopic features in the presence of intracytoplasmic, spherical, eosinophilic inclusion bodies. Previous electron microscopic studies have shown these bodies to consist of fibrils; bundles of fibrils have also been described in the cytoplasm. We have examined one such tumor, confirmed earlier findings, and established that the component cells are typical myofibroblasts. The latter are a variety of fibroblasts first described in granulation tissue; they are endowed with contractile properties and are characterized ultrastructurally by bundles of fibrils containing \"dense bodies\" such as are found in smooth muscle cells. Since our case is identical to those previously described, we propose that this tumor be called infantile digital myofibroblastoma.", "contents": "A myofibroblastic tumor. Infantile digital fibroma (recurrent digital fibrous tumor of childhood). Infantile digital fibromas are distinctive tumors both clinically and morphologically. A unique light microscopic features in the presence of intracytoplasmic, spherical, eosinophilic inclusion bodies. Previous electron microscopic studies have shown these bodies to consist of fibrils; bundles of fibrils have also been described in the cytoplasm. We have examined one such tumor, confirmed earlier findings, and established that the component cells are typical myofibroblasts. The latter are a variety of fibroblasts first described in granulation tissue; they are endowed with contractile properties and are characterized ultrastructurally by bundles of fibrils containing \"dense bodies\" such as are found in smooth muscle cells. Since our case is identical to those previously described, we propose that this tumor be called infantile digital myofibroblastoma."}
{"id": "PMID:216268", "title": "Revisions in the microscopic method of estimating age at death in human cortical bone.", "content": "Problems recently discovered in the Kerley method of estimating age at death from cortical microstructure are discussed. Kerley's original data have been re-analyzed to produce new regression equations and to document the original field size.", "contents": "Revisions in the microscopic method of estimating age at death in human cortical bone. Problems recently discovered in the Kerley method of estimating age at death from cortical microstructure are discussed. Kerley's original data have been re-analyzed to produce new regression equations and to document the original field size."}
{"id": "PMID:216269", "title": "Involvement of cGMP in LHRH-stimulated gonadotropin release.", "content": "Anterior pituitary content of cyclic AMP (cAMP) and cyclic GMP (cGMP) has been measured during stimulation of gonadotropin release by luteinizing-hormone-releasing hormone (LHRH) in vitro to gain more information concerning the relationship between the mechanism of action of LHRH and cyclic nucleotides. During the increased gonadotropin release obtained by incubation by hemipituitaries with LHRH (0.25--25 X 10(-9) M) for 180 min, the glands taken from both male and female rats exhibited increased cGMP content, whereas cAMP content rose only in those taken from male rats. The increase in cGMP content was observed after only 2 min in the presence of LHRH (5 X 10(-9) M) and prior to augmented gonadotropin release. The increase in cAMP content in the male glands was detectable only after 60 min of incubation. These results suggest that cGMP might be involved in the mechanism of action of LHRH.", "contents": "Involvement of cGMP in LHRH-stimulated gonadotropin release. Anterior pituitary content of cyclic AMP (cAMP) and cyclic GMP (cGMP) has been measured during stimulation of gonadotropin release by luteinizing-hormone-releasing hormone (LHRH) in vitro to gain more information concerning the relationship between the mechanism of action of LHRH and cyclic nucleotides. During the increased gonadotropin release obtained by incubation by hemipituitaries with LHRH (0.25--25 X 10(-9) M) for 180 min, the glands taken from both male and female rats exhibited increased cGMP content, whereas cAMP content rose only in those taken from male rats. The increase in cGMP content was observed after only 2 min in the presence of LHRH (5 X 10(-9) M) and prior to augmented gonadotropin release. The increase in cAMP content in the male glands was detectable only after 60 min of incubation. These results suggest that cGMP might be involved in the mechanism of action of LHRH."}
{"id": "PMID:216270", "title": "Arginine vasopressin metabolism in dogs. I. Evidence for a receptor-mediated mechanism.", "content": "The plasma clearance rates (PCR) of arginine vasopressin (AVP), and iodinated AVP (125I-AVP) were determined after pulse injection in conscious water-loaded dogs. Both the PCR and the apparent initial volume of distribution were significantly greater for AVP than for the biologically inactive iodinated AVP 37.4 +/- 4.8 ml/kg per min vs. 6.7 +/- 0.8 ml/kg per min (P less than 0.001) and 12.7 +/- 0.9% body wt vs. 7.1 +/- 0.4% body wt (P less than 0.001). AVP clearance was then determined by the constant-infusion technique at doses that produced equilibrium AVP concentrations within and above the physiological range. AVP-PCR was 37.4 +/- 7.1 ml/kg per min at 34 microU/kg per min, which was comparable to that after pulse injection (P less than 0.9). AVP clearance fell progressively, and urine osmolality progressively increased with increasing AVP infusion rates to plateau values at 136 microU/kg per min; a strong negative correlation was observed between mean AVP-PCR and urine osmolality (r = -0.993). The data suggest a relationship between the biological activity of AVP and its clearance. It is proposed that plasma membrane receptors may mediate a portion of the metabolic clearance of AVP.", "contents": "Arginine vasopressin metabolism in dogs. I. Evidence for a receptor-mediated mechanism. The plasma clearance rates (PCR) of arginine vasopressin (AVP), and iodinated AVP (125I-AVP) were determined after pulse injection in conscious water-loaded dogs. Both the PCR and the apparent initial volume of distribution were significantly greater for AVP than for the biologically inactive iodinated AVP 37.4 +/- 4.8 ml/kg per min vs. 6.7 +/- 0.8 ml/kg per min (P less than 0.001) and 12.7 +/- 0.9% body wt vs. 7.1 +/- 0.4% body wt (P less than 0.001). AVP clearance was then determined by the constant-infusion technique at doses that produced equilibrium AVP concentrations within and above the physiological range. AVP-PCR was 37.4 +/- 7.1 ml/kg per min at 34 microU/kg per min, which was comparable to that after pulse injection (P less than 0.9). AVP clearance fell progressively, and urine osmolality progressively increased with increasing AVP infusion rates to plateau values at 136 microU/kg per min; a strong negative correlation was observed between mean AVP-PCR and urine osmolality (r = -0.993). The data suggest a relationship between the biological activity of AVP and its clearance. It is proposed that plasma membrane receptors may mediate a portion of the metabolic clearance of AVP."}
{"id": "PMID:216271", "title": "Arginine vasopressin metabolism in dogs. II. Modeling and system analysis.", "content": "System modeling and analysis methods were applied to interpret data regarding arginine vasopressin (AVP) metabolism in dogs. Based on this analysis a new nonlinear 3-pool model of AVP distribution and disposal was proposed and quantified; the model pools included the plasma, a receptor pool, and an extravascular nonreceptor pool. The receptor pool mediated a portion of the rapid flux of hormone between the plasma and the extravascular pool. Mathematical analysis indicated that the plasma AVP impulse response (bolus) data would be insufficient to uniquely estimate all the model constants, but additional plasma impulse data using 125I-labeled AVP, which does not bind to physiologic hormone receptors, would allow unique model quantification. Other required measurements were the urinary excretion of intact hormone, and plasma AVP degradation. The model was successfully fitted to the data from 10 dogs. The results suggest that, in the normal dogs studied, plasma contained 25% of the total AVP, 19% was bound to receptors, and the remaining 56% was in the extravascular pool. Eighty percent of the flux of AVP from the vascular compartment was mediated by the receptor pool; 98% of AVP degradation occurred in the extravascular pool; and urine excretion and plasma degradation made up the remainder.", "contents": "Arginine vasopressin metabolism in dogs. II. Modeling and system analysis. System modeling and analysis methods were applied to interpret data regarding arginine vasopressin (AVP) metabolism in dogs. Based on this analysis a new nonlinear 3-pool model of AVP distribution and disposal was proposed and quantified; the model pools included the plasma, a receptor pool, and an extravascular nonreceptor pool. The receptor pool mediated a portion of the rapid flux of hormone between the plasma and the extravascular pool. Mathematical analysis indicated that the plasma AVP impulse response (bolus) data would be insufficient to uniquely estimate all the model constants, but additional plasma impulse data using 125I-labeled AVP, which does not bind to physiologic hormone receptors, would allow unique model quantification. Other required measurements were the urinary excretion of intact hormone, and plasma AVP degradation. The model was successfully fitted to the data from 10 dogs. The results suggest that, in the normal dogs studied, plasma contained 25% of the total AVP, 19% was bound to receptors, and the remaining 56% was in the extravascular pool. Eighty percent of the flux of AVP from the vascular compartment was mediated by the receptor pool; 98% of AVP degradation occurred in the extravascular pool; and urine excretion and plasma degradation made up the remainder."}
{"id": "PMID:216273", "title": "Cholinergic agents inhibit sodium transport across the isolated toad bladder.", "content": "Acetylcholine and carbamylcholine (carbachol) inhibited sodium transport across the toad bladder. This effect was blocked by atropine. Carbachol increased the uptake of 45Ca by isolated toad bladder epithelial cells. This increased 45Ca uptake was blocked by atropine, pentobarbital, or lanthanum chloride. The inhibitory effect of cholinergic agents on sodium transport was dependent on external calcium concentration and was abolished by decreasing external calcium from 2 to 0.2 mM or by agents (pentobarbital, lanthanum chloride) which prevent the movement of calcium into cells. Carbachol increased modestly, but significantly, the levels of cyclic GMP in isolated toad bladder epithelial cells. This effect was blocked by atropine. Whether the decrease in sodium transport produced by cholinergic agents is the result of increased intracytoplasmic calcium levels, increased cyclic GMP levels, or a combination of both remains to be established.", "contents": "Cholinergic agents inhibit sodium transport across the isolated toad bladder. Acetylcholine and carbamylcholine (carbachol) inhibited sodium transport across the toad bladder. This effect was blocked by atropine. Carbachol increased the uptake of 45Ca by isolated toad bladder epithelial cells. This increased 45Ca uptake was blocked by atropine, pentobarbital, or lanthanum chloride. The inhibitory effect of cholinergic agents on sodium transport was dependent on external calcium concentration and was abolished by decreasing external calcium from 2 to 0.2 mM or by agents (pentobarbital, lanthanum chloride) which prevent the movement of calcium into cells. Carbachol increased modestly, but significantly, the levels of cyclic GMP in isolated toad bladder epithelial cells. This effect was blocked by atropine. Whether the decrease in sodium transport produced by cholinergic agents is the result of increased intracytoplasmic calcium levels, increased cyclic GMP levels, or a combination of both remains to be established."}
{"id": "PMID:216274", "title": "Long-term effects of traumatic war-related events on sleep.", "content": "Eleven patients who had combat neuroses resulting from the 1973 Yom Kippur War and complained of sleep disturbances were studied in a sleep laboratory. Sleep-onset insomniacs, dream-interruption insomniacs, and pseudoinsomniacs were differentiated on the basis of electrophysiologic recordings. Compared with normal controls who actively participated in the Yom Kippur War, patients showed significantly longer sleep latencies, lower sleep efficiency indices, lower percentage of REM sleep, and longer REM latencies.", "contents": "Long-term effects of traumatic war-related events on sleep. Eleven patients who had combat neuroses resulting from the 1973 Yom Kippur War and complained of sleep disturbances were studied in a sleep laboratory. Sleep-onset insomniacs, dream-interruption insomniacs, and pseudoinsomniacs were differentiated on the basis of electrophysiologic recordings. Compared with normal controls who actively participated in the Yom Kippur War, patients showed significantly longer sleep latencies, lower sleep efficiency indices, lower percentage of REM sleep, and longer REM latencies."}
{"id": "PMID:216275", "title": "Psychiatric services in Soviet general outpatient clinics.", "content": "The author believes that the first level of psychiatric care in the U.S.S.R.--the general polyclinics (outpatient clinics) and the medical-sanitary units--have not been adequately studied. He describes this level of care, which is considered useful and progressive in that the clinics are supposed to make psychiatric care available to the population, lighten the load placed on psychiatric facilities, and improve follow-up therapy. However, he also points out the shortcomings in this first level of psychiatric care in the U.S.S.R., including the bureaucratic nature of the system and the uneven quality of service the clinics render to various social groups in urban and rural areas.", "contents": "Psychiatric services in Soviet general outpatient clinics. The author believes that the first level of psychiatric care in the U.S.S.R.--the general polyclinics (outpatient clinics) and the medical-sanitary units--have not been adequately studied. He describes this level of care, which is considered useful and progressive in that the clinics are supposed to make psychiatric care available to the population, lighten the load placed on psychiatric facilities, and improve follow-up therapy. However, he also points out the shortcomings in this first level of psychiatric care in the U.S.S.R., including the bureaucratic nature of the system and the uneven quality of service the clinics render to various social groups in urban and rural areas."}
{"id": "PMID:216276", "title": "Malakoplakia. Two unusual cases which presented diagnostic problems.", "content": "Two unusual cases of malakoplakia are presented. Both cases occurred outside the urinary tract (retroperitoneum and anus) and were diagnostic problems due to the paucity of Michaelis-Guttman bodies. One case mimicked a retroperitoneal malignant fibrous histiocytoma and the other a common perianal abcess.", "contents": "Malakoplakia. Two unusual cases which presented diagnostic problems. Two unusual cases of malakoplakia are presented. Both cases occurred outside the urinary tract (retroperitoneum and anus) and were diagnostic problems due to the paucity of Michaelis-Guttman bodies. One case mimicked a retroperitoneal malignant fibrous histiocytoma and the other a common perianal abcess."}
{"id": "PMID:216277", "title": "Rhabdomyosarcoma arising within a cystosarcoma phyllodes. Case report and review of the literature.", "content": "Rhabdomyosarcoma of the breast is a rare tumor that is characterized by its rapid growth, large size, and poor prognosis. It most often presents as a pure neoplasm and infrequently as the stromal component of a cystosarcoma phyllodes. The clinical and pathological features of a cystosarcoma with a rhabdomyosarcomatous stroma occurring in a 45-year-old woman are presented, and the results are discussed in reference to the 24 published cases of mammary rhabdomyosarcoma. The patient was treated by radical mastectomy and died 2.5 years later with pulmonary and cerebral metastases. Though two long-term survivors have been reported, cures are infrequent and no form of therapy has been uniformly successful.", "contents": "Rhabdomyosarcoma arising within a cystosarcoma phyllodes. Case report and review of the literature. Rhabdomyosarcoma of the breast is a rare tumor that is characterized by its rapid growth, large size, and poor prognosis. It most often presents as a pure neoplasm and infrequently as the stromal component of a cystosarcoma phyllodes. The clinical and pathological features of a cystosarcoma with a rhabdomyosarcomatous stroma occurring in a 45-year-old woman are presented, and the results are discussed in reference to the 24 published cases of mammary rhabdomyosarcoma. The patient was treated by radical mastectomy and died 2.5 years later with pulmonary and cerebral metastases. Though two long-term survivors have been reported, cures are infrequent and no form of therapy has been uniformly successful."}
{"id": "PMID:216280", "title": "Radioactive and nonradioactive methods for the in vivo determination of disulfiram, diethyldithiocarbamate, and diethyldithiocarbamate-methyl ester.", "content": "Although disulfiram (tetraethylthiuram disulfide; DSF) has been used in the treatment of alcoholism for almost a quarter of a century, little is known about its in vivo metabolism. One reason for this is that few analytical methods are available that can determine DSF and its various metabolites in biologic fluids and tissues. This article describes two simple procedures for the determination of these substances.", "contents": "Radioactive and nonradioactive methods for the in vivo determination of disulfiram, diethyldithiocarbamate, and diethyldithiocarbamate-methyl ester. Although disulfiram (tetraethylthiuram disulfide; DSF) has been used in the treatment of alcoholism for almost a quarter of a century, little is known about its in vivo metabolism. One reason for this is that few analytical methods are available that can determine DSF and its various metabolites in biologic fluids and tissues. This article describes two simple procedures for the determination of these substances."}
{"id": "PMID:216281", "title": "Methods for detecting disulfiram in biologic fluids: application in studies of compliance and effect of divalent cations on bioavailability.", "content": "Studies regarding the efficacy of disulfiram in the treatment of alcoholism have not included a method of evaluating compliance to the prescribed regimen. This article outlines current methods used to detect disulfiram in blood, breath, and urine.", "contents": "Methods for detecting disulfiram in biologic fluids: application in studies of compliance and effect of divalent cations on bioavailability. Studies regarding the efficacy of disulfiram in the treatment of alcoholism have not included a method of evaluating compliance to the prescribed regimen. This article outlines current methods used to detect disulfiram in blood, breath, and urine."}
{"id": "PMID:216284", "title": "Characterization of Sertoli cell-germ cell junctional specializations in dissociated testicular cells.", "content": "To further characterize Sertoli cell-germ cell junctional specializations seminiferous tubules from sexually mature Sprague-Dawley rats were dissociated by enzymatic and mechanical methods. Ultrastructural analysis of cell suspensions prepared by incubation in collagenase alone or by mechanical methods revealed that spermatids remained attached to Sertoli cells or Sertoli cell fragments. Such cellular associations were found only between Sertoli cell fragments and spematids in which the developing acrosome had made contact with the plasma membrane (step 8 and subsequent steps of spermiogenesis). Furthermore, the fragments were confined to that region of the plasma membrane over the acrosome. The Sertoli cell half of this adhesive site displayed the typical elements of Sertoli cell junctions, filamentous bundles and associated cisterna of endoplasmic reticulum, in apposition to the spermatids. The spermatids demonstrated no surface specializations at the attachment sites. In contrast, in cell suspensions prepared with trypsin, spermatids were free of attachments to Sertoli cells or their fragments. These results demonstrate that: (1) the junctions act to bind cells together, (2) adhesive type contact is established between Sertoli cells and spermatids at step 8 and subsequent steps of spermiogenesis, (3) contact is restricted to the spermatid plasma membrane over the acrosome, and (4) spermatids can be freed from the junctional specializations by treatment with trypsin.", "contents": "Characterization of Sertoli cell-germ cell junctional specializations in dissociated testicular cells. To further characterize Sertoli cell-germ cell junctional specializations seminiferous tubules from sexually mature Sprague-Dawley rats were dissociated by enzymatic and mechanical methods. Ultrastructural analysis of cell suspensions prepared by incubation in collagenase alone or by mechanical methods revealed that spermatids remained attached to Sertoli cells or Sertoli cell fragments. Such cellular associations were found only between Sertoli cell fragments and spematids in which the developing acrosome had made contact with the plasma membrane (step 8 and subsequent steps of spermiogenesis). Furthermore, the fragments were confined to that region of the plasma membrane over the acrosome. The Sertoli cell half of this adhesive site displayed the typical elements of Sertoli cell junctions, filamentous bundles and associated cisterna of endoplasmic reticulum, in apposition to the spermatids. The spermatids demonstrated no surface specializations at the attachment sites. In contrast, in cell suspensions prepared with trypsin, spermatids were free of attachments to Sertoli cells or their fragments. These results demonstrate that: (1) the junctions act to bind cells together, (2) adhesive type contact is established between Sertoli cells and spermatids at step 8 and subsequent steps of spermiogenesis, (3) contact is restricted to the spermatid plasma membrane over the acrosome, and (4) spermatids can be freed from the junctional specializations by treatment with trypsin."}
{"id": "PMID:216285", "title": "Ultracytochemical localization of Na+,K+-activated ATPase in chloride cells from the gills of a euryhaline teleost.", "content": "The activity of the electrolyte transport enzyme, sodium, potassium-activated adenosine triphosphatase (Na+,K+-ATPase), in the gills of the pinfish, Lagodon rhomboides, increased markedly following transfer of fish from brackish water to seawater. Cytochemical localization of Na+,K+-ATPase via its potassium-dependent phosphatase (K+-NPPase) activity in the branchial epithelium of pinfish adapted to seawater demonstrated that chloride cells are the major sites for the enzyme. Subcellularly, the heaviest depositions of reaction product were observed lining the cytoplasmic membrane surfaces of the labyrinth of anastomosing plasma membrane tubules that ramifies throughout the chloride cell cytoplasm. Enzyme activity was demonstrated also on the cytoplasmic surface of the apical crypt membrane and on the cytoplasmic surfaces of vesicles in the cytoplasm subjacent to the crypt. Deletion of potassium from the cytochemical incubation medium or inclusion of 10 mM ouabain abolished the reaction products associated with these membranes. The significance of these cytochemical results is discussed with reference to current hypotheses of chloride cell function.", "contents": "Ultracytochemical localization of Na+,K+-activated ATPase in chloride cells from the gills of a euryhaline teleost. The activity of the electrolyte transport enzyme, sodium, potassium-activated adenosine triphosphatase (Na+,K+-ATPase), in the gills of the pinfish, Lagodon rhomboides, increased markedly following transfer of fish from brackish water to seawater. Cytochemical localization of Na+,K+-ATPase via its potassium-dependent phosphatase (K+-NPPase) activity in the branchial epithelium of pinfish adapted to seawater demonstrated that chloride cells are the major sites for the enzyme. Subcellularly, the heaviest depositions of reaction product were observed lining the cytoplasmic membrane surfaces of the labyrinth of anastomosing plasma membrane tubules that ramifies throughout the chloride cell cytoplasm. Enzyme activity was demonstrated also on the cytoplasmic surface of the apical crypt membrane and on the cytoplasmic surfaces of vesicles in the cytoplasm subjacent to the crypt. Deletion of potassium from the cytochemical incubation medium or inclusion of 10 mM ouabain abolished the reaction products associated with these membranes. The significance of these cytochemical results is discussed with reference to current hypotheses of chloride cell function."}
{"id": "PMID:216288", "title": "Effects of Haemophilus influenzae vaccination on the (para-)sympathic-cyclic nucleotide-histamine axis in rats.", "content": "To determine whether Haemophilus influenzae could be a factor in human atopy its effects were studied on the (para-)Sympathic Cyclic nucleotide-histamine axis in rats. Haemophilus influenzae vaccination induced changes in the cholinergic system compatible with higher cyclic GMP levels and enhanced histamine release. The authors suggest an involvement of the cholinergic system in Haemophilus influenzae vaccination effects.", "contents": "Effects of Haemophilus influenzae vaccination on the (para-)sympathic-cyclic nucleotide-histamine axis in rats. To determine whether Haemophilus influenzae could be a factor in human atopy its effects were studied on the (para-)Sympathic Cyclic nucleotide-histamine axis in rats. Haemophilus influenzae vaccination induced changes in the cholinergic system compatible with higher cyclic GMP levels and enhanced histamine release. The authors suggest an involvement of the cholinergic system in Haemophilus influenzae vaccination effects."}
{"id": "PMID:216289", "title": "[Antigen enzyme coupling: a few results (author's transl)].", "content": "Various technics of coupling (carbodiimide, glutaraldehyde, periodate) have been used for the grafting of human casein on glucose oxidase. The various types of product obtained were identified by gel filtration and used for drawing up titration curves. The authors compared radioimmunoassay and enzymoimmunologic estimation showing the importance of the molecular size of the conjugates obtained.", "contents": "[Antigen enzyme coupling: a few results (author's transl)]. Various technics of coupling (carbodiimide, glutaraldehyde, periodate) have been used for the grafting of human casein on glucose oxidase. The various types of product obtained were identified by gel filtration and used for drawing up titration curves. The authors compared radioimmunoassay and enzymoimmunologic estimation showing the importance of the molecular size of the conjugates obtained."}
{"id": "PMID:216290", "title": "Canine plasma cortisol (hydrocortisone) measured by radioimmunoassay: clinical absence of diurnal variation and results of ACTH stimulation and dexamethasone suppression tests.", "content": "A radioimmunoassay for plasma cortisol (hydrocortisone) was developed and validated for sensitivity, specificity, accuracy, precision, and parallelism. Steroids were extracted with ethyl ether, and cortisol was purified by gel column chromatography prior to assay. [1,2-3H] cortisol and a commercially available sheep antibody to cortisol-21-hemisuccinate were used. Free steriods were separated from bound steroids by centrifugation after adsorption to dextran-coated charcoal. Plasma cortisol was measured by this technique in 6 normal dogs. Circadian rhythm of cortisol secretion was not detected in samples obtained by venipuncture at 8 different hours on 3 separate days, suggesting that adrenal function tests may be started in clinical patients at any time of day. Resting plasma cortisol concentrations averaged 19.4+/-3.0 (SD) ng/ml and ranged from nondetectable (less than 3 ng/ml) to 77.5 ng/ml. Of 144 canine plasma samples, 95% contained less than 50 ng of cortisol/ml. Intramuscular injection of 2.2 units of adrenocorticotropic hormone/kg of body weight caused detectable increase in plasma cortisol concentrations; maximum response (68.3 to 111.6 ng/ml) occurred 1 to 2 hours after injection. Oral administration of dexamethasone suppressed plasma cortisol to nondetectable concentrations for 32 hours in all 6 dogs.", "contents": "Canine plasma cortisol (hydrocortisone) measured by radioimmunoassay: clinical absence of diurnal variation and results of ACTH stimulation and dexamethasone suppression tests. A radioimmunoassay for plasma cortisol (hydrocortisone) was developed and validated for sensitivity, specificity, accuracy, precision, and parallelism. Steroids were extracted with ethyl ether, and cortisol was purified by gel column chromatography prior to assay. [1,2-3H] cortisol and a commercially available sheep antibody to cortisol-21-hemisuccinate were used. Free steriods were separated from bound steroids by centrifugation after adsorption to dextran-coated charcoal. Plasma cortisol was measured by this technique in 6 normal dogs. Circadian rhythm of cortisol secretion was not detected in samples obtained by venipuncture at 8 different hours on 3 separate days, suggesting that adrenal function tests may be started in clinical patients at any time of day. Resting plasma cortisol concentrations averaged 19.4+/-3.0 (SD) ng/ml and ranged from nondetectable (less than 3 ng/ml) to 77.5 ng/ml. Of 144 canine plasma samples, 95% contained less than 50 ng of cortisol/ml. Intramuscular injection of 2.2 units of adrenocorticotropic hormone/kg of body weight caused detectable increase in plasma cortisol concentrations; maximum response (68.3 to 111.6 ng/ml) occurred 1 to 2 hours after injection. Oral administration of dexamethasone suppressed plasma cortisol to nondetectable concentrations for 32 hours in all 6 dogs."}
{"id": "PMID:216292", "title": "Simple method for preparation of specific antisera against viral proteins: rabbit antisera against equine infectious anemia virus proteins p26 and p16.", "content": "A simple method for preparation of highly specific antisera against equine infectious anemia virus proteins p26 and p16 is described. Viral proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The motility of the viral proteins in the gel was compared with standards. Unstained portions of the slab gel were sliced into 5-mm bands, emulsified with Freund's complete adjuvant, and injected into rabbits to produce specific antisera.", "contents": "Simple method for preparation of specific antisera against viral proteins: rabbit antisera against equine infectious anemia virus proteins p26 and p16. A simple method for preparation of highly specific antisera against equine infectious anemia virus proteins p26 and p16 is described. Viral proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The motility of the viral proteins in the gel was compared with standards. Unstained portions of the slab gel were sliced into 5-mm bands, emulsified with Freund's complete adjuvant, and injected into rabbits to produce specific antisera."}
{"id": "PMID:216296", "title": "Recurrent hemorrhage in traumatic hyphema.", "content": "A retrospective review of hospital records reveals that over 90% of recurrent bleeds in traumatic hyphema occur at night. It is postulated that rapid eye movement (REM) sleep, with its displays of saccadic virtuosity, is the major reason for the nocturnal prevalence of such recurrent hyphemas. Theoretical considerations suggesting a more rational therapy of traumatic hyphema are presented and clinical trials are suggested.", "contents": "Recurrent hemorrhage in traumatic hyphema. A retrospective review of hospital records reveals that over 90% of recurrent bleeds in traumatic hyphema occur at night. It is postulated that rapid eye movement (REM) sleep, with its displays of saccadic virtuosity, is the major reason for the nocturnal prevalence of such recurrent hyphemas. Theoretical considerations suggesting a more rational therapy of traumatic hyphema are presented and clinical trials are suggested."}
{"id": "PMID:216300", "title": "Serum and CSF antibody levels to herpes simplex type 1, measles and rubella viruses in patients with schizophrenia.", "content": "Serum and CSF specimens from 12 schizophrenic patients and 10 non-psychiatric controls were tested for herpes simplex type 1 virus neutralizing antibody and for measles and rubella haemagglutination inhibiting antibodies. There were no significant differences in the distribution of virus antibody titres in serum or CSF specimens between the patients and the controls. The possible aetiological role of viruses or virus-like agents in schizophrenia and some methodological aspects are discussed.", "contents": "Serum and CSF antibody levels to herpes simplex type 1, measles and rubella viruses in patients with schizophrenia. Serum and CSF specimens from 12 schizophrenic patients and 10 non-psychiatric controls were tested for herpes simplex type 1 virus neutralizing antibody and for measles and rubella haemagglutination inhibiting antibodies. There were no significant differences in the distribution of virus antibody titres in serum or CSF specimens between the patients and the controls. The possible aetiological role of viruses or virus-like agents in schizophrenia and some methodological aspects are discussed."}
{"id": "PMID:216297", "title": "[Blue rubber bleb nevus (author's transl)].", "content": "Hereditary dysembryoplasia, the B. R. B. N. (Bean, 1958) is a variety of bluish nevus of the skin, associated with angioma of the gastrointestinal tract with serious bleeding, and sometimes of liver, spleen, bones, brain, marrow. The angiomas of the skin may occur in 3 forms: large cavernous angiomas; blood sac looking like a blue rubber nipple, they can be emptied; irregular blue mark, sometimes with puncted blackish spots, they may not blanch on pressure. They are painful. glomus-like angioma cavernous angioma. Ultrastructure: cavity with endothelial cells and one to four coats of smooth muscle cells. The angiomas arose in the submucous cellular tissue, projected into the cavity of the bowel, sometimes bleeding. Hematemesis and melena may be observed as in the Rendu-Osler disease. They nver spontaneously involve but they don't degenerate. The prognosis depends essentially on the bleedings and anemia. It is possible to cut out the skin angiomas.", "contents": "[Blue rubber bleb nevus (author's transl)]. Hereditary dysembryoplasia, the B. R. B. N. (Bean, 1958) is a variety of bluish nevus of the skin, associated with angioma of the gastrointestinal tract with serious bleeding, and sometimes of liver, spleen, bones, brain, marrow. The angiomas of the skin may occur in 3 forms: large cavernous angiomas; blood sac looking like a blue rubber nipple, they can be emptied; irregular blue mark, sometimes with puncted blackish spots, they may not blanch on pressure. They are painful. glomus-like angioma cavernous angioma. Ultrastructure: cavity with endothelial cells and one to four coats of smooth muscle cells. The angiomas arose in the submucous cellular tissue, projected into the cavity of the bowel, sometimes bleeding. Hematemesis and melena may be observed as in the Rendu-Osler disease. They nver spontaneously involve but they don't degenerate. The prognosis depends essentially on the bleedings and anemia. It is possible to cut out the skin angiomas."}
{"id": "PMID:216302", "title": "Chiasmal syndrome in sphenoid sinus mucocele.", "content": "Two patients with sphenoethmoid mucoceles developed visual field defects consistent with optic chiasm dysfunction. The presence of chiasmal field defects associated with the clinical syndrome of compressive optic neuropathy should not rule out the diagnosis of sphenoethmoid mucocele since definitive treatment can be carried out via transnasal drainage.", "contents": "Chiasmal syndrome in sphenoid sinus mucocele. Two patients with sphenoethmoid mucoceles developed visual field defects consistent with optic chiasm dysfunction. The presence of chiasmal field defects associated with the clinical syndrome of compressive optic neuropathy should not rule out the diagnosis of sphenoethmoid mucocele since definitive treatment can be carried out via transnasal drainage."}
{"id": "PMID:216303", "title": "Endogenous pain control mechanisms: review and hypothesis.", "content": "The anatomy, physiology, and pharmacology of an intrinsic neural network that monitors and modulates the activity of pain-transmitting neurons is reviewed. This system can be activated by opiate administration or by electrical stimulation of discrete brainstem sites. Evidence is presented that its pain-suppressing action is mediated in part by endogenous opiatelike compounds (endorphins). This pain suppression system is organized at three levels of the neuraxis: midbrain, medulla, and spinal cord. Activation of neurons in the midbrain periaqueductal gray matter (by electrical stimulation, opiates, and possibly psychological factors) excites neurons of the rostral medulla, some of which contain serotonin. The medullary neurons, in turn, project to and specifically inhibit the firing of trigeminal and spinal pain-transmission neurons. As part of a negative feedback loop, the output of the pain transmission neurons, i.e., pain itself, is an important factor in activating the pain-suppression system. A neural model which incorporates the experimental findings is proposed, and the clinical implications of the model are discussed.", "contents": "Endogenous pain control mechanisms: review and hypothesis. The anatomy, physiology, and pharmacology of an intrinsic neural network that monitors and modulates the activity of pain-transmitting neurons is reviewed. This system can be activated by opiate administration or by electrical stimulation of discrete brainstem sites. Evidence is presented that its pain-suppressing action is mediated in part by endogenous opiatelike compounds (endorphins). This pain suppression system is organized at three levels of the neuraxis: midbrain, medulla, and spinal cord. Activation of neurons in the midbrain periaqueductal gray matter (by electrical stimulation, opiates, and possibly psychological factors) excites neurons of the rostral medulla, some of which contain serotonin. The medullary neurons, in turn, project to and specifically inhibit the firing of trigeminal and spinal pain-transmission neurons. As part of a negative feedback loop, the output of the pain transmission neurons, i.e., pain itself, is an important factor in activating the pain-suppression system. A neural model which incorporates the experimental findings is proposed, and the clinical implications of the model are discussed."}
{"id": "PMID:216301", "title": "[Study of the hypothalamo-pituitary adrenal function in 16 patients after surgery for pituitary tumor (author's transl)].", "content": "The hypothalamic pituitary adrenocortical function has been studied in 16 patients operated from pituitary tumors (13 adenomas; 3 craniopharyngiomas). Comparisons have been made between corticotropin and cortisol response to lysine vasopressin, insulin induced-hypoglycemia and metyrapone IV and per os. Among these different stimulating tests, insulin induced hypoglycemia and metyrapone per os seem to give the more accurate informations metyrapone per os being more convenient because harmless. Three different groups of patients have been distinguished : one without adrenocortical deficiency; one with a complete deficiency and a third group with a partial deficiency. Correlations have been studied between the degree of the adrenocortical deficiency, the volume of the tumor and the presence of the absence of other anterior pituitary dysfunctions.", "contents": "[Study of the hypothalamo-pituitary adrenal function in 16 patients after surgery for pituitary tumor (author's transl)]. The hypothalamic pituitary adrenocortical function has been studied in 16 patients operated from pituitary tumors (13 adenomas; 3 craniopharyngiomas). Comparisons have been made between corticotropin and cortisol response to lysine vasopressin, insulin induced-hypoglycemia and metyrapone IV and per os. Among these different stimulating tests, insulin induced hypoglycemia and metyrapone per os seem to give the more accurate informations metyrapone per os being more convenient because harmless. Three different groups of patients have been distinguished : one without adrenocortical deficiency; one with a complete deficiency and a third group with a partial deficiency. Correlations have been studied between the degree of the adrenocortical deficiency, the volume of the tumor and the presence of the absence of other anterior pituitary dysfunctions."}
{"id": "PMID:216305", "title": "Correlation between hemin content and the chemiluminescent luminol reaction with bacteria.", "content": "Protohemin and covalently bound hemin were determined in eight aerobic bacterial strains. A good correlation between protohemin content and luminol reactivity was found. The ratio of luminol reaction to protohemin for the eight investigated strains was essentially identical to that of pure protohemin, 0.7 X 10(16) mV/mol. Covalently bound hemin contributed to the chemiluminescence to a minor extent only (0.7 X 10(14) mV/mol, in accordance with earlier observations of the lower reactivity of cytochrome c and related compounds. A difference in reaction kinetics of the luminol reaction with covalently bound hemin (slower reaction than protohemin) and protohemin was observed in vivo as well as in vitro. The phenomenon could be used to differentiate between strains with different hemin composition.", "contents": "Correlation between hemin content and the chemiluminescent luminol reaction with bacteria. Protohemin and covalently bound hemin were determined in eight aerobic bacterial strains. A good correlation between protohemin content and luminol reactivity was found. The ratio of luminol reaction to protohemin for the eight investigated strains was essentially identical to that of pure protohemin, 0.7 X 10(16) mV/mol. Covalently bound hemin contributed to the chemiluminescence to a minor extent only (0.7 X 10(14) mV/mol, in accordance with earlier observations of the lower reactivity of cytochrome c and related compounds. A difference in reaction kinetics of the luminol reaction with covalently bound hemin (slower reaction than protohemin) and protohemin was observed in vivo as well as in vitro. The phenomenon could be used to differentiate between strains with different hemin composition."}
{"id": "PMID:216306", "title": "High levels of microbial contamination of vegetables irrigated with wastewater by the drip method.", "content": "The public health aspects of the use of wastewater in agriculture and the effects of the drip irrigation method on the contamination of vegetables were studied. The method used was to simulate enteric microorganisms' dissemination by contaminated irrigation water in the field. The vegetables were irrigated with an effluent inoculated with a high titer of traceable microorganisms: poliovirus vaccine and a drug-resistant Escherichia coli. The dissemination of the marker organisms in the field was followed, and the effects of certain manipulations of the drip irrigation method on the contamination of the crops by the effluent were examined. It was shown that drip irrigation under plastic sheet cover with the drip lines placed either on the soil surface or buried at a depth of 10 cm significantly reduced crop contamination from inoculated irrigation water even when massive doses of bacteria and viruses were used. The microbial contamination was found to persist in the irrigation pipes and in the soil for at least 8 and 18 days, respectively. The data indicate that the recovery of the marker organisms was affected by soil texture and environmental conditions.", "contents": "High levels of microbial contamination of vegetables irrigated with wastewater by the drip method. The public health aspects of the use of wastewater in agriculture and the effects of the drip irrigation method on the contamination of vegetables were studied. The method used was to simulate enteric microorganisms' dissemination by contaminated irrigation water in the field. The vegetables were irrigated with an effluent inoculated with a high titer of traceable microorganisms: poliovirus vaccine and a drug-resistant Escherichia coli. The dissemination of the marker organisms in the field was followed, and the effects of certain manipulations of the drip irrigation method on the contamination of the crops by the effluent were examined. It was shown that drip irrigation under plastic sheet cover with the drip lines placed either on the soil surface or buried at a depth of 10 cm significantly reduced crop contamination from inoculated irrigation water even when massive doses of bacteria and viruses were used. The microbial contamination was found to persist in the irrigation pipes and in the soil for at least 8 and 18 days, respectively. The data indicate that the recovery of the marker organisms was affected by soil texture and environmental conditions."}
{"id": "PMID:216307", "title": "Growth and methanogenesis by Methanosarcina strain 227 on acetate and methanol.", "content": "Methanosarcina strain 227 exhibited exponential growth on sodium acetate in the absence of added H(2). Under these conditions, rates of methanogenesis were limited by concentrations of acetate below 0.05 M. One mole of methane was formed per mole of acetate consumed. Additional evidence from radioactive labeling studies indicated that sufficient energy for growth was obtained by the decarboxylation of acetate. Diauxic growth and sequential methanogenesis from methanol followed by acetate occurred in the presence of mixtures of methanol and acetate. Detailed studies showed that methanol-grown cells did not metabolize acetate in the presence of methanol, although acetate-grown cells did metabolize methanol and acetate simultaneously before shifting to methanol. Acetate catabolism appeared to be regulated in response to the presence of better metabolizable substrates such as methanol or H(2)-CO(2) by a mechanism resembling catabolite repression. Inhibition of methanogenesis from acetate by 2-bromoethanesulfonate, an analog of coenzyme M, was reversed by addition of coenzyme M. Labeling studies also showed that methanol may lie on the acetate pathway. These results suggested that methanogenesis from acetate, methanol, and H(2)-CO(2) may have some steps in common, as originally proposed by Barker. Studies with various inhibitors, together with molar growth yield data, suggest a role for electron transport mechanisms in energy metabolism during methanogenesis from methanol, acetate, and H(2)-CO(2).", "contents": "Growth and methanogenesis by Methanosarcina strain 227 on acetate and methanol. Methanosarcina strain 227 exhibited exponential growth on sodium acetate in the absence of added H(2). Under these conditions, rates of methanogenesis were limited by concentrations of acetate below 0.05 M. One mole of methane was formed per mole of acetate consumed. Additional evidence from radioactive labeling studies indicated that sufficient energy for growth was obtained by the decarboxylation of acetate. Diauxic growth and sequential methanogenesis from methanol followed by acetate occurred in the presence of mixtures of methanol and acetate. Detailed studies showed that methanol-grown cells did not metabolize acetate in the presence of methanol, although acetate-grown cells did metabolize methanol and acetate simultaneously before shifting to methanol. Acetate catabolism appeared to be regulated in response to the presence of better metabolizable substrates such as methanol or H(2)-CO(2) by a mechanism resembling catabolite repression. Inhibition of methanogenesis from acetate by 2-bromoethanesulfonate, an analog of coenzyme M, was reversed by addition of coenzyme M. Labeling studies also showed that methanol may lie on the acetate pathway. These results suggested that methanogenesis from acetate, methanol, and H(2)-CO(2) may have some steps in common, as originally proposed by Barker. Studies with various inhibitors, together with molar growth yield data, suggest a role for electron transport mechanisms in energy metabolism during methanogenesis from methanol, acetate, and H(2)-CO(2)."}
{"id": "PMID:216308", "title": "Identification of detergents as components of wastewater sludge that modify the thermal stability of reovirus and enteroviruses.", "content": "The agent in wastewater sludge previously shown to reduce the heat required to inactivate reovirus (R. L. Ward and C. S. Ashley, Appl. Environ. Microbiol. 34:681--688, 1977) was \"separated\" from other sludge components and analyzed by infrared spectroscopy. The infrared spectrum of this material was quite similar to the spectra of commercial anionic detergents, and subsequent analyses of the fractionated sludge samples revealed that anionic detergents in sludge were copurified with the virucidal activity. Further measurements on the virucidal activities of specific detergents revealed that ionic detergents reduce the heat required to inactivate reovirus, that cationic detergents are more active than anionic, and that nonionic detergents are inactive. Several detergents were also shown to protect poliovirus and other enteroviruses against inactivation by heat. These results indicate that ionic detergents are the major component in wastewater sludge that reduce the thermal stability of reovirus and, in addition, that detergents are able to protect enteroviruses against heat.", "contents": "Identification of detergents as components of wastewater sludge that modify the thermal stability of reovirus and enteroviruses. The agent in wastewater sludge previously shown to reduce the heat required to inactivate reovirus (R. L. Ward and C. S. Ashley, Appl. Environ. Microbiol. 34:681--688, 1977) was \"separated\" from other sludge components and analyzed by infrared spectroscopy. The infrared spectrum of this material was quite similar to the spectra of commercial anionic detergents, and subsequent analyses of the fractionated sludge samples revealed that anionic detergents in sludge were copurified with the virucidal activity. Further measurements on the virucidal activities of specific detergents revealed that ionic detergents reduce the heat required to inactivate reovirus, that cationic detergents are more active than anionic, and that nonionic detergents are inactive. Several detergents were also shown to protect poliovirus and other enteroviruses against inactivation by heat. These results indicate that ionic detergents are the major component in wastewater sludge that reduce the thermal stability of reovirus and, in addition, that detergents are able to protect enteroviruses against heat."}
{"id": "PMID:216309", "title": "Heat inactivation of enteric viruses in dewatered wastewater sludge.", "content": "The effect of moisture content on the rates of heat inactivation of enteric viruses in wastewater sludge was determined. The protective effect of raw sludge on poliovirus previously observed (R. L. Ward, C. S. Ashley, and R. H. Moseley, Appl. Environ. Microbiol. 32:339--346, 1976) was found to be greatly enhanced in sludge dewatered by evaporation. Other enteroviruses responded in a similar fashion. This effect did not appear to be due merely to the state of dryness of the sludge samples because in humus-deficient soil, a relatively inert material, the rate of poliovirus inactivation by heat was not significantly altered through dewatering. Instead, this effect appeared to have been caused by protective substances in the sludge, such as detergents, which are concentrated through dewatering. As reported previously (R. L. Ward and C. S. Ashley, Appl. Environ. Microbiol. 34:681-688, 1977; R. L. Ward and C. S. Ashley, Appl. Environ. Microbiol 36:889--897, 1978) raw sludge is not protective of reovirus, but, instead, the ionic detergents in sludge cause the rate of heat inactivation of this virus to be accelerated. Dewatering of sludge, however, was found to partially reverse this virucidal effect. Evidence is presented indicating that this reversal is caused by an unidentified protective substance in sludge also concentrated through dewatering. Finally, it was shown that the effects of raw sludge on heat inactivation of poliovirus and reovirus are greatly reduced by composting, a result that correlated with the degradation of detergents.", "contents": "Heat inactivation of enteric viruses in dewatered wastewater sludge. The effect of moisture content on the rates of heat inactivation of enteric viruses in wastewater sludge was determined. The protective effect of raw sludge on poliovirus previously observed (R. L. Ward, C. S. Ashley, and R. H. Moseley, Appl. Environ. Microbiol. 32:339--346, 1976) was found to be greatly enhanced in sludge dewatered by evaporation. Other enteroviruses responded in a similar fashion. This effect did not appear to be due merely to the state of dryness of the sludge samples because in humus-deficient soil, a relatively inert material, the rate of poliovirus inactivation by heat was not significantly altered through dewatering. Instead, this effect appeared to have been caused by protective substances in the sludge, such as detergents, which are concentrated through dewatering. As reported previously (R. L. Ward and C. S. Ashley, Appl. Environ. Microbiol. 34:681-688, 1977; R. L. Ward and C. S. Ashley, Appl. Environ. Microbiol 36:889--897, 1978) raw sludge is not protective of reovirus, but, instead, the ionic detergents in sludge cause the rate of heat inactivation of this virus to be accelerated. Dewatering of sludge, however, was found to partially reverse this virucidal effect. Evidence is presented indicating that this reversal is caused by an unidentified protective substance in sludge also concentrated through dewatering. Finally, it was shown that the effects of raw sludge on heat inactivation of poliovirus and reovirus are greatly reduced by composting, a result that correlated with the degradation of detergents."}
{"id": "PMID:216310", "title": "Membrane filter enumeration method for Clostridium perfringens.", "content": "A membrane filter procedure has been developed for the rapid quantitation of C. perfringens in the aquatic environment. Background growth is inhibited by the use of D-cycloserine, polymyxin B sulfate, and incubation at 45 degrees C. Differential characteristics include the fermentation of sucrose, production of acid phosphatase, and the absence of beta-D-glucosidase activity. The medium is prepared as follows (in grams per 100 ml of distilled water): tryptose, 3.0; yeast extract, 2.0; sucrose, 0.5; L-cysteine, 0.1; MgSO4. 7H2O, 0.01; bromocresol purple, 0.004; and agar, 1.5. The ingredients are dissolved, and the pH is adjusted to 7.6. After autoclaving at 121 degrees C for 15 min, the medium is allowed to cool at 50 degrees C, and the following are added per 100 ml: D-cycloserine, 40 mg; polymyxin B sulfate, 2.5 mg; indoxyl-beta-D-glucoside, 60 mg; 2.0 ml of a filter-sterilized 0.5% phenolpthalein diphosphate solution; and 0.2 ml of a filter-sterilized 4.5% FeCl3.6H2O solution. Enumeration of C. perfringens in a water sample is completed within 18 to 24 h. The verification of typical colonies was 93%. The average recovery from peptone-water spore suspensions of five strains was 79%, and that from filter-sterilized seawater suspensions was 90%. The precision of the method was approximately equal to that expected from random error alone. Confirmed recoveries of C. perfringens from water and sewage samples generally were greater than those by the Bonde pour tube method.", "contents": "Membrane filter enumeration method for Clostridium perfringens. A membrane filter procedure has been developed for the rapid quantitation of C. perfringens in the aquatic environment. Background growth is inhibited by the use of D-cycloserine, polymyxin B sulfate, and incubation at 45 degrees C. Differential characteristics include the fermentation of sucrose, production of acid phosphatase, and the absence of beta-D-glucosidase activity. The medium is prepared as follows (in grams per 100 ml of distilled water): tryptose, 3.0; yeast extract, 2.0; sucrose, 0.5; L-cysteine, 0.1; MgSO4. 7H2O, 0.01; bromocresol purple, 0.004; and agar, 1.5. The ingredients are dissolved, and the pH is adjusted to 7.6. After autoclaving at 121 degrees C for 15 min, the medium is allowed to cool at 50 degrees C, and the following are added per 100 ml: D-cycloserine, 40 mg; polymyxin B sulfate, 2.5 mg; indoxyl-beta-D-glucoside, 60 mg; 2.0 ml of a filter-sterilized 0.5% phenolpthalein diphosphate solution; and 0.2 ml of a filter-sterilized 4.5% FeCl3.6H2O solution. Enumeration of C. perfringens in a water sample is completed within 18 to 24 h. The verification of typical colonies was 93%. The average recovery from peptone-water spore suspensions of five strains was 79%, and that from filter-sterilized seawater suspensions was 90%. The precision of the method was approximately equal to that expected from random error alone. Confirmed recoveries of C. perfringens from water and sewage samples generally were greater than those by the Bonde pour tube method."}
{"id": "PMID:216320", "title": "[Tumour regression in pituitary adenoma by bromocriptin (author's transl)].", "content": "A 35 year old patient with longstanding amenorrhea-galactorrhea due to a pituitary macroadenoma has been observed for a period of more than 2 years. During this time tumour expansion was radiologically evident. A full term pregnancy was responsible for most of the tumour growth. Following postpartum period Bromocriptin treatment led to considerable regression of the adenoma. Recalcification of sella structures and an involuted sella volume was radiologically evident. With reference to the experimental investigations of Lloyd (1975) and following the suggestions of L'Hermite (1977) and Vaidya (1977) this tumour regression is interpreted as being due to the antimitotic effect of Bromocriptin via inhibition of c-AMP and DNA.", "contents": "[Tumour regression in pituitary adenoma by bromocriptin (author's transl)]. A 35 year old patient with longstanding amenorrhea-galactorrhea due to a pituitary macroadenoma has been observed for a period of more than 2 years. During this time tumour expansion was radiologically evident. A full term pregnancy was responsible for most of the tumour growth. Following postpartum period Bromocriptin treatment led to considerable regression of the adenoma. Recalcification of sella structures and an involuted sella volume was radiologically evident. With reference to the experimental investigations of Lloyd (1975) and following the suggestions of L'Hermite (1977) and Vaidya (1977) this tumour regression is interpreted as being due to the antimitotic effect of Bromocriptin via inhibition of c-AMP and DNA."}
{"id": "PMID:216323", "title": "Jaundice after renal allotransplantation.", "content": "Of 567 patients receiving renal transplantation at the University of Minnesota between October 1967 and October 1975, 22 developed clinical jaundice. Of these 22, nine died with their initial episode of hepatitis, six died within three months of causes associated with liver malfunction, four developed evidence of chronic hepatic failure and only three totally recovered from their illness. Five had clear evidence of Australia antigen positive hepatitis B, four of cytomegalovirus hepatitis, two of herpes hominis hepatitis, one of varicella zoster hepatitis and three of hepatic failure associated with systemic bacterial and/or fungal sepsis. Two of the 22 patients were thought likely to have cytomegalovirus hepatitis though definite proof was absent and in five patients a clear-cut etiology could not be made. In many of these patients the diagnosis was confounded by the previous presence of HB(s)Ag antigen and the frequent occurrence of a previous or concurrent infection with cytomegalovirus. The role of various drugs including azathioprine, sulfisoxazole, chlorpromazine, acetominophen, etc., could not be established but major roles for these agents in the face of the many viral and bacterial infections present in these patients is doubted. No clear-cut therapy could be established although it appears safe to discontinue azathioprine for longer or shorter periods of time with or without substitution of cyclophosphamide without serious deterioration of renal function. The problem of hepatic failure in transplant patients is still unsolved and will require a prospective study of etiologic agents and sub-clinical hepatic dysfunction in order to establish even the first principles of clinical-pathological correlation.", "contents": "Jaundice after renal allotransplantation. Of 567 patients receiving renal transplantation at the University of Minnesota between October 1967 and October 1975, 22 developed clinical jaundice. Of these 22, nine died with their initial episode of hepatitis, six died within three months of causes associated with liver malfunction, four developed evidence of chronic hepatic failure and only three totally recovered from their illness. Five had clear evidence of Australia antigen positive hepatitis B, four of cytomegalovirus hepatitis, two of herpes hominis hepatitis, one of varicella zoster hepatitis and three of hepatic failure associated with systemic bacterial and/or fungal sepsis. Two of the 22 patients were thought likely to have cytomegalovirus hepatitis though definite proof was absent and in five patients a clear-cut etiology could not be made. In many of these patients the diagnosis was confounded by the previous presence of HB(s)Ag antigen and the frequent occurrence of a previous or concurrent infection with cytomegalovirus. The role of various drugs including azathioprine, sulfisoxazole, chlorpromazine, acetominophen, etc., could not be established but major roles for these agents in the face of the many viral and bacterial infections present in these patients is doubted. No clear-cut therapy could be established although it appears safe to discontinue azathioprine for longer or shorter periods of time with or without substitution of cyclophosphamide without serious deterioration of renal function. The problem of hepatic failure in transplant patients is still unsolved and will require a prospective study of etiologic agents and sub-clinical hepatic dysfunction in order to establish even the first principles of clinical-pathological correlation."}
{"id": "PMID:216324", "title": "Action of p-(4-amidino-phenoxy)-benzaldehyde-p-amidino-phenylhydrazone dihydrochloride on Leishmania donovani infections in the golden hamster.", "content": "The chemotherapeutic effect of a new diamidine, HOE 668, the p-(4-amidino-phenoxy)-benzaldehyde-p-amidino-phenylhydrazone dihydrochloride, was compared with that of known anti-leishmanial drugs in golden hamsters infected with Leishmania donovani. The effect of HOE 668 against visceral leishmaniasis proved superior to that of pentamidine isethionate and the pentavalent antimonial drugs, sodium stibogluconate and N-methylglucamine antimoniate. However, HOE 668 can be used only experimentally because of its toxicity. Its very good anti-leishmanial action qualifies HOE 668 as a standard compound in screening tests.", "contents": "Action of p-(4-amidino-phenoxy)-benzaldehyde-p-amidino-phenylhydrazone dihydrochloride on Leishmania donovani infections in the golden hamster. The chemotherapeutic effect of a new diamidine, HOE 668, the p-(4-amidino-phenoxy)-benzaldehyde-p-amidino-phenylhydrazone dihydrochloride, was compared with that of known anti-leishmanial drugs in golden hamsters infected with Leishmania donovani. The effect of HOE 668 against visceral leishmaniasis proved superior to that of pentamidine isethionate and the pentavalent antimonial drugs, sodium stibogluconate and N-methylglucamine antimoniate. However, HOE 668 can be used only experimentally because of its toxicity. Its very good anti-leishmanial action qualifies HOE 668 as a standard compound in screening tests."}
{"id": "PMID:216325", "title": "The interaction between Entamoeba histolytica and Syphacia obvelata infection in mice.", "content": "Mice naturally infected with Syphacia obvelata were challenged intracaecally with Entamoeba histolytica trophozoites. They showed a higher level of amoebic infection than mice without worms. Mice with the heaviest Syphacia infection were the most susceptible to amoebic infection. It appears that a concomitant infection with helminthic parasites residing in the caecum alters the outcome of an amoebic infection.", "contents": "The interaction between Entamoeba histolytica and Syphacia obvelata infection in mice. Mice naturally infected with Syphacia obvelata were challenged intracaecally with Entamoeba histolytica trophozoites. They showed a higher level of amoebic infection than mice without worms. Mice with the heaviest Syphacia infection were the most susceptible to amoebic infection. It appears that a concomitant infection with helminthic parasites residing in the caecum alters the outcome of an amoebic infection."}
{"id": "PMID:216327", "title": "Action of phenylbutazone, cyclophosphamide and prednacinolone on pleurisy due to Bordetella pertussis hypersensitivity in the rat.", "content": "Phenylbutazone, cyclophosphamide and prednacinolone acetonide, administered around the period of challenge reduced the exudate of pleurisy due to Bordetella pertussis hypersensitivity in the rat. The results on the leukocytes of the exudate are different depending on the class of product studied. Phenylbutazone only slightly reduced the number of mononuclears cells. Both the immunosuppressive and the corticoid induced a clear decrease in the total leukocyte number. But, while prednacinolone effects were nearly equally distributed among mononuclears and polynuclears, cyclophosphamide was mainly active on mononuclears.", "contents": "Action of phenylbutazone, cyclophosphamide and prednacinolone on pleurisy due to Bordetella pertussis hypersensitivity in the rat. Phenylbutazone, cyclophosphamide and prednacinolone acetonide, administered around the period of challenge reduced the exudate of pleurisy due to Bordetella pertussis hypersensitivity in the rat. The results on the leukocytes of the exudate are different depending on the class of product studied. Phenylbutazone only slightly reduced the number of mononuclears cells. Both the immunosuppressive and the corticoid induced a clear decrease in the total leukocyte number. But, while prednacinolone effects were nearly equally distributed among mononuclears and polynuclears, cyclophosphamide was mainly active on mononuclears."}
{"id": "PMID:216328", "title": "Increase in urinary excretion of phosphates, hydroxyproline, and cAMP during acetate desoxycorticosterone + saline treatment in the rat.", "content": "We investigated the urinary excretion of phosphates, hydroxyproline, and cAMP in rats treated with desoxycorticosterone acetate (DOCA) associated with a hypersaline diet. We measured the three substances in groups with or without parathyroid or thyroid glands, or both. Urinary phosphate excretion increased greatly during the first weeks of treatment in normal rats and in rats autografted with parathyroids and lacking thyroid, and increased slightly in the groups without parathyroids. Hydroxyproline and cAMP had the same pattern; their excretion was greatest during week 2 of treatment in all groups, but these phenomena were more intense in animals with parathyroids. These fact support the conclusion that the parathyroid glands are stimulated during the start of mineralocorticoid-saline treatment.", "contents": "Increase in urinary excretion of phosphates, hydroxyproline, and cAMP during acetate desoxycorticosterone + saline treatment in the rat. We investigated the urinary excretion of phosphates, hydroxyproline, and cAMP in rats treated with desoxycorticosterone acetate (DOCA) associated with a hypersaline diet. We measured the three substances in groups with or without parathyroid or thyroid glands, or both. Urinary phosphate excretion increased greatly during the first weeks of treatment in normal rats and in rats autografted with parathyroids and lacking thyroid, and increased slightly in the groups without parathyroids. Hydroxyproline and cAMP had the same pattern; their excretion was greatest during week 2 of treatment in all groups, but these phenomena were more intense in animals with parathyroids. These fact support the conclusion that the parathyroid glands are stimulated during the start of mineralocorticoid-saline treatment."}
{"id": "PMID:216329", "title": "Progesterone therapy in obese patients with sleep apnea.", "content": "Seven morbidly obese patients with sleep-related upper airway obstruction (UAO) were studied before and during progesterone treatment. All subjects had severe daytime somnolence, and five of the seven had congestive heart failure. All subjects were studied for one or two consecutive baseline nights in the sleep laboratory. Six of the seven subjects showed a mean of greater than 100 UAOs. Patients were treated for two to four weeks with medroxyprogesterone acetate, 20 mg three times daily. At the end of the treatment period, the sleep studies were repeated. There was no significant difference in the incidence, mean duration, or rate per minute of apneic episodes occurring before and with progesterone treatment. Severe hypoxemia during sleep persisted with treatment, as did the occurrence of cardiac arrhythmias. There was a significant improvement in the waking Pao2 with progesterone treatment.", "contents": "Progesterone therapy in obese patients with sleep apnea. Seven morbidly obese patients with sleep-related upper airway obstruction (UAO) were studied before and during progesterone treatment. All subjects had severe daytime somnolence, and five of the seven had congestive heart failure. All subjects were studied for one or two consecutive baseline nights in the sleep laboratory. Six of the seven subjects showed a mean of greater than 100 UAOs. Patients were treated for two to four weeks with medroxyprogesterone acetate, 20 mg three times daily. At the end of the treatment period, the sleep studies were repeated. There was no significant difference in the incidence, mean duration, or rate per minute of apneic episodes occurring before and with progesterone treatment. Severe hypoxemia during sleep persisted with treatment, as did the occurrence of cardiac arrhythmias. There was a significant improvement in the waking Pao2 with progesterone treatment."}
{"id": "PMID:216330", "title": "Some observations on the opiate peptides and schizophrenia.", "content": "With the discovery of the opiate peptides, several major avenues of research became apparent. These peptides produced a great deal of focused attention on their anatomy, biochemistry, and physiology. In this article, we present an overview of some of the main research issues and recent findings in the field of opiate peptides. The possible relationship of the opiate peptide neuronal systems to schizophrenia is discussed in light of attempts to alter schizophrenic symptoms with opiate antagonists, beta-endorphin, and dialysis. It is hypothesized that if the opiate peptides are involved in schizophrenia, then their involvement with dopamine systems and/or with stress responses may be critical.", "contents": "Some observations on the opiate peptides and schizophrenia. With the discovery of the opiate peptides, several major avenues of research became apparent. These peptides produced a great deal of focused attention on their anatomy, biochemistry, and physiology. In this article, we present an overview of some of the main research issues and recent findings in the field of opiate peptides. The possible relationship of the opiate peptide neuronal systems to schizophrenia is discussed in light of attempts to alter schizophrenic symptoms with opiate antagonists, beta-endorphin, and dialysis. It is hypothesized that if the opiate peptides are involved in schizophrenia, then their involvement with dopamine systems and/or with stress responses may be critical."}
{"id": "PMID:216331", "title": "Successful separation of depressed, normal, and insomniac subjects by EEG sleep data.", "content": "Data from all-night EEG sleep studies were used to distinguish normal subjects, primary depressed patients, and primary insomniac patients. In part 1, we compared 41 normal subjects, 56 depressed patients, and 18 insomniacs. In a univariate comparison with normal subjects, depressed patients showed less total sleep, longer sleep latency, more early morning awake time, more intermittent awake time, less delta sleep, less sleep efficiency, and shorter rapid eye movement (REM) latencies; compared with insomniacs, depressed patients showed greater early morning awake time, shorter REM latency, greater REM index, and greater REM density. Using multivariate discriminant analysis, 82% of the sample were correctly classified by diagnosis: 100% of the normal subjects, 72% of the depressed patients, and 77% of the insomniacs. Eight variables contributed to the multivariate separation of depressed individuals from insomniacs and normals: total sleep time, total recording period, sleep efficiency, sleep latency, early morning awake time, awake time, REM time and REM%. When the discriminant functions were applied to a second group of 18 primary depressed patients, 82% were correctly classified as depressed. These results suggest that primary depressed patients and primary insomniac patients may show relatively characteristic patterns of sleep abnormality.", "contents": "Successful separation of depressed, normal, and insomniac subjects by EEG sleep data. Data from all-night EEG sleep studies were used to distinguish normal subjects, primary depressed patients, and primary insomniac patients. In part 1, we compared 41 normal subjects, 56 depressed patients, and 18 insomniacs. In a univariate comparison with normal subjects, depressed patients showed less total sleep, longer sleep latency, more early morning awake time, more intermittent awake time, less delta sleep, less sleep efficiency, and shorter rapid eye movement (REM) latencies; compared with insomniacs, depressed patients showed greater early morning awake time, shorter REM latency, greater REM index, and greater REM density. Using multivariate discriminant analysis, 82% of the sample were correctly classified by diagnosis: 100% of the normal subjects, 72% of the depressed patients, and 77% of the insomniacs. Eight variables contributed to the multivariate separation of depressed individuals from insomniacs and normals: total sleep time, total recording period, sleep efficiency, sleep latency, early morning awake time, awake time, REM time and REM%. When the discriminant functions were applied to a second group of 18 primary depressed patients, 82% were correctly classified as depressed. These results suggest that primary depressed patients and primary insomniac patients may show relatively characteristic patterns of sleep abnormality."}
{"id": "PMID:216333", "title": "[Monoamine metabolites and cyclic nucleotides in the cerebrospinal fluid of patients with bismuth or mercury poisoning].", "content": "The central metabolism of dopamine, serotonin, cyclic AMP and cyclic GMP was studied by use of the probenecid test in three patients with bismuth encephalopathy and in one patient with mercury encephalopathy. The accumulation of HVA and of cGMP in the cerebrospinal fluid was depressed during the acute phase of bismuth encephalopathy with severe hyposomnia, while it was increased in a patient with regression of clinical symptoms and normal in a patient with more advanced recovery. The patient with chronic mercury poisoning showing a severe cerebellar ataxia and rigidity had an almost complete suppression of HVA accumulation and an increase of cGMP accumulation. No pronounced differences of 5-HIAA and cAMP behavior were found. It is concluded that the central metabolism of dopamine and of cGMP is severely affected in bismuth and mercury encephalopathies.", "contents": "[Monoamine metabolites and cyclic nucleotides in the cerebrospinal fluid of patients with bismuth or mercury poisoning]. The central metabolism of dopamine, serotonin, cyclic AMP and cyclic GMP was studied by use of the probenecid test in three patients with bismuth encephalopathy and in one patient with mercury encephalopathy. The accumulation of HVA and of cGMP in the cerebrospinal fluid was depressed during the acute phase of bismuth encephalopathy with severe hyposomnia, while it was increased in a patient with regression of clinical symptoms and normal in a patient with more advanced recovery. The patient with chronic mercury poisoning showing a severe cerebellar ataxia and rigidity had an almost complete suppression of HVA accumulation and an increase of cGMP accumulation. No pronounced differences of 5-HIAA and cAMP behavior were found. It is concluded that the central metabolism of dopamine and of cGMP is severely affected in bismuth and mercury encephalopathies."}
{"id": "PMID:216334", "title": "The effect of dextransulfate 500 on the pathogenesis of herpes simplex virus infections in weanling mice.", "content": "Intraperitoneal (i.p.) injection of Dextran Sulfate (D.S.) 500 during a limited period of time influences the course of herpes simplex-virus-infections. D.S.500 was found to reduce the resistance of mice for some herpes simplex-virus strains (Len, L3--2s, Haase) if given between 16 hours and 2 hours after i.p. infection. The decrease of resistance could be correlated with an increase of the virus content of liver, spleen, brain and spinal cord. Injection of herpes simplex-virus-specific immune serum counteracted the effect of D.S.500 on the course of infections. Conversely, D.S.500 increased the resistance of mice to another group of herpes simplex-viruses (strains D-316, Thea, DD), if given 3 to 8 hours before infection. These effects are ascribed to a special interaction of D.S.500 with macrophages and probably other virus-susceptible cells of the peritoneal cavity and elsewhere with a resulting counteraction to the virus infection.", "contents": "The effect of dextransulfate 500 on the pathogenesis of herpes simplex virus infections in weanling mice. Intraperitoneal (i.p.) injection of Dextran Sulfate (D.S.) 500 during a limited period of time influences the course of herpes simplex-virus-infections. D.S.500 was found to reduce the resistance of mice for some herpes simplex-virus strains (Len, L3--2s, Haase) if given between 16 hours and 2 hours after i.p. infection. The decrease of resistance could be correlated with an increase of the virus content of liver, spleen, brain and spinal cord. Injection of herpes simplex-virus-specific immune serum counteracted the effect of D.S.500 on the course of infections. Conversely, D.S.500 increased the resistance of mice to another group of herpes simplex-viruses (strains D-316, Thea, DD), if given 3 to 8 hours before infection. These effects are ascribed to a special interaction of D.S.500 with macrophages and probably other virus-susceptible cells of the peritoneal cavity and elsewhere with a resulting counteraction to the virus infection."}
{"id": "PMID:216335", "title": "Stimulation of host DNA synthesis and induction of early antigens by ultraviolet light irradiated human cytomegalovirus.", "content": "The ultraviolet (UV-)sensitivity of the human cytomegalovirus (HCMV) genes coding for very early complement fixing and early antigens in human embryonic fibroblasts (HEF) and mouse embryonic fibroblasts (MEF) and the relation of these genes to the ability of the virus to stimulate host cell DNA synthesis were investigated. After 14 minutes of UV-irradiation of the virus inoculum only the very early complement fixing nuclear antigen (CMNA) developed in the HEF cells and only the early cytoplasmic antigen(s) was present in the MEF. In both HEF and MEF, host cell DNA synthesis was stimulated. We conclude that the ability of HCMV to stimulate host DNA synthesis is an early function of the viral genome and shows a high resistance to UV-irradiation. There is no direct correlation, however, between the ability of the virus to stimulate host cell DNA synthesis and the genes which code for the CMNA or for early cytoplasmic antigens.", "contents": "Stimulation of host DNA synthesis and induction of early antigens by ultraviolet light irradiated human cytomegalovirus. The ultraviolet (UV-)sensitivity of the human cytomegalovirus (HCMV) genes coding for very early complement fixing and early antigens in human embryonic fibroblasts (HEF) and mouse embryonic fibroblasts (MEF) and the relation of these genes to the ability of the virus to stimulate host cell DNA synthesis were investigated. After 14 minutes of UV-irradiation of the virus inoculum only the very early complement fixing nuclear antigen (CMNA) developed in the HEF cells and only the early cytoplasmic antigen(s) was present in the MEF. In both HEF and MEF, host cell DNA synthesis was stimulated. We conclude that the ability of HCMV to stimulate host DNA synthesis is an early function of the viral genome and shows a high resistance to UV-irradiation. There is no direct correlation, however, between the ability of the virus to stimulate host cell DNA synthesis and the genes which code for the CMNA or for early cytoplasmic antigens."}
{"id": "PMID:216336", "title": "Reversible inhibition of the induction of DNA polymerase of herpes simplex virus type 2 in HeLa cells.", "content": "The induction of DNA polymerase of herpes simplex virus type 2 in HeLa cells was inhibited by 2-mercapto-1-(beta-4-pyridethyl)benzimidazole added at an early time after infection. However, the inhibitory effect was easily released by removal of the inhibitor. Since the drug disorganizes nucleolar structure and prevents its function in HeLa cells in a reversible manner, it is possible that nucleoli are involved in the induction of DNA polymerase of this virus.", "contents": "Reversible inhibition of the induction of DNA polymerase of herpes simplex virus type 2 in HeLa cells. The induction of DNA polymerase of herpes simplex virus type 2 in HeLa cells was inhibited by 2-mercapto-1-(beta-4-pyridethyl)benzimidazole added at an early time after infection. However, the inhibitory effect was easily released by removal of the inhibitor. Since the drug disorganizes nucleolar structure and prevents its function in HeLa cells in a reversible manner, it is possible that nucleoli are involved in the induction of DNA polymerase of this virus."}
{"id": "PMID:216337", "title": "[Patterns of cytomegaly generalization and its pathomorphological diagnosis].", "content": "On the basis of morphological examinations of 576 cases of cytomegalia, several summarizing statements concerning the regularities of its generalization are presented. According to the nature of tissue reactions in the salivary glands which correlatively depend on the status of immunogenesis organs and the form of the disease, 4 morphological types of cytomegalic sialoadenitis are distinguished: nodular, immunodeficient, persisting, and hemopoietic. It is recommended that the discovered regularities be taken into consideration in autopsy practice which will permit to minimize the cases of unrecognized generalization of the infection.", "contents": "[Patterns of cytomegaly generalization and its pathomorphological diagnosis]. On the basis of morphological examinations of 576 cases of cytomegalia, several summarizing statements concerning the regularities of its generalization are presented. According to the nature of tissue reactions in the salivary glands which correlatively depend on the status of immunogenesis organs and the form of the disease, 4 morphological types of cytomegalic sialoadenitis are distinguished: nodular, immunodeficient, persisting, and hemopoietic. It is recommended that the discovered regularities be taken into consideration in autopsy practice which will permit to minimize the cases of unrecognized generalization of the infection."}
{"id": "PMID:216338", "title": "[Histochemical characteristics of the mucus in pseudomyxoma peritonei].", "content": "Histochemical investigations of gelatinous masses of 3 patients with pseudomyxoma peritonei were carried out. The tissues of the mucinous adenocarcinoma of the ovary and normal appendix were used for comparison. The results showed that the mucus in pseudomyxoma peritonei as well as that of the epithelial cells of the appendix belonged to the group of acid nonsulfurated mucoid substances of epithelial origin rich in syalic acid. The mucus in the mucinous adenocarcinoma of the ovary had the same histochemical properties, except for its resistance to neuraminidase. Some suggestions on the pathogenetic mechanisms of the development of the disease and possibilities of therapeutic applications of neuraminidase are presented.", "contents": "[Histochemical characteristics of the mucus in pseudomyxoma peritonei]. Histochemical investigations of gelatinous masses of 3 patients with pseudomyxoma peritonei were carried out. The tissues of the mucinous adenocarcinoma of the ovary and normal appendix were used for comparison. The results showed that the mucus in pseudomyxoma peritonei as well as that of the epithelial cells of the appendix belonged to the group of acid nonsulfurated mucoid substances of epithelial origin rich in syalic acid. The mucus in the mucinous adenocarcinoma of the ovary had the same histochemical properties, except for its resistance to neuraminidase. Some suggestions on the pathogenetic mechanisms of the development of the disease and possibilities of therapeutic applications of neuraminidase are presented."}
{"id": "PMID:216340", "title": "[Mucoepidermoid tumor of the epipharynx].", "content": "Case report about a mukoepidermoid-tumor, which was investigated by means of histology and electron microscopy. The localisation of this tumor in the epipharynx is a rarity and unknown in the literature. The variable differentiated tumor consists of epidermoid cells with different graduation of maturity, of epithelial cells from the gland ducts and primitive acini as well as in the majority of undifferentiated cell types. The tumor seems to be of a \"low grade malignity\".", "contents": "[Mucoepidermoid tumor of the epipharynx]. Case report about a mukoepidermoid-tumor, which was investigated by means of histology and electron microscopy. The localisation of this tumor in the epipharynx is a rarity and unknown in the literature. The variable differentiated tumor consists of epidermoid cells with different graduation of maturity, of epithelial cells from the gland ducts and primitive acini as well as in the majority of undifferentiated cell types. The tumor seems to be of a \"low grade malignity\"."}
{"id": "PMID:216341", "title": "Coxsackie myocarditis complicating treatment of Hodgkin's lymphoma.", "content": "A fatal case of Coxsackie B4 myocarditis complicating treatment of Hodgkin's lymphoma in an adult is reported. The virus was isolated from the myocardium obtained at autopsy and light microscopy confirmed a myocarditis with involvement of the conduction system. Electron-microscopy showed dense mitochondrial inclusions. Coxsackie myocarditis rarely results in death of affected adults. It is postulated in this case that the treatment of the Hodgkin's lymphoma resulted in B lymphocyte depletion, allowing a more virulent infection to occur with resultant fatal myocarditis.", "contents": "Coxsackie myocarditis complicating treatment of Hodgkin's lymphoma. A fatal case of Coxsackie B4 myocarditis complicating treatment of Hodgkin's lymphoma in an adult is reported. The virus was isolated from the myocardium obtained at autopsy and light microscopy confirmed a myocarditis with involvement of the conduction system. Electron-microscopy showed dense mitochondrial inclusions. Coxsackie myocarditis rarely results in death of affected adults. It is postulated in this case that the treatment of the Hodgkin's lymphoma resulted in B lymphocyte depletion, allowing a more virulent infection to occur with resultant fatal myocarditis."}
{"id": "PMID:216342", "title": "Pitfalls in carpal tunnel decompression.", "content": "In the period 1972 to 1977, 35 patients with persistent pain and other disabilities after carpal tunnel decompression were referred for treatment. The pitfalls included: (i) wrong diagnosis--5 patients; (ii) inadequate decompression--9 patients; (iii) recurrent compression--4 patients; (iv) iatrogenic nerve injury--7 patients; and (v) postoperative complications--10 patients. The patients in Groups 1 and 5 were treated by non-operative measures. Most of the patients in Groups 2, 3, and 4 were treated by reoperation. This paper outlines the causes and prevention of pitfalls in carpal tunnel decompression.", "contents": "Pitfalls in carpal tunnel decompression. In the period 1972 to 1977, 35 patients with persistent pain and other disabilities after carpal tunnel decompression were referred for treatment. The pitfalls included: (i) wrong diagnosis--5 patients; (ii) inadequate decompression--9 patients; (iii) recurrent compression--4 patients; (iv) iatrogenic nerve injury--7 patients; and (v) postoperative complications--10 patients. The patients in Groups 1 and 5 were treated by non-operative measures. Most of the patients in Groups 2, 3, and 4 were treated by reoperation. This paper outlines the causes and prevention of pitfalls in carpal tunnel decompression."}
{"id": "PMID:216346", "title": "Esterases of Mus musculus: substrate and inhibition characteristics, new isozymes, and homologies with man.", "content": "A wide range of fluorogenic and naphthol esters has been tested as substrates for mouse esterases. New esterases have been identified in liver and kidney extracts with palmityl, oleyl, and elaidyl esters. From substrate, inhibition, and molecular weight studies, three homologies between human and mouse esterases are suggested. A new allele at Es-6 is also described.", "contents": "Esterases of Mus musculus: substrate and inhibition characteristics, new isozymes, and homologies with man. A wide range of fluorogenic and naphthol esters has been tested as substrates for mouse esterases. New esterases have been identified in liver and kidney extracts with palmityl, oleyl, and elaidyl esters. From substrate, inhibition, and molecular weight studies, three homologies between human and mouse esterases are suggested. A new allele at Es-6 is also described."}
{"id": "PMID:216347", "title": "Intrasubunit nucleotide binding in ribonucleic acid polymerase.", "content": "1. Periodate oxidation of the ribose ring was used to synthesize derivatives of nucleoside triphosphates. 2. These oxidized nucleoside triphosphates. 2. These oxidized nucleoside triphosphates are competitive inhibitors of RNA polymerase. 3. On incubation, together with NaBH4, these oxidized labelled nucleotides are covalently bound to Escherichia coli RNA polymerase. 4. Nucleoside triphosphate substrates decrease the extent of labelling. 5. A lysine residue in an alpha-subunit is labelled. 6. The significance of these results in relation to the location of the nucleotide-binding site is discussed.", "contents": "Intrasubunit nucleotide binding in ribonucleic acid polymerase. 1. Periodate oxidation of the ribose ring was used to synthesize derivatives of nucleoside triphosphates. 2. These oxidized nucleoside triphosphates. 2. These oxidized nucleoside triphosphates are competitive inhibitors of RNA polymerase. 3. On incubation, together with NaBH4, these oxidized labelled nucleotides are covalently bound to Escherichia coli RNA polymerase. 4. Nucleoside triphosphate substrates decrease the extent of labelling. 5. A lysine residue in an alpha-subunit is labelled. 6. The significance of these results in relation to the location of the nucleotide-binding site is discussed."}
{"id": "PMID:216348", "title": "alpha-L-iduronate ring conformations in heparin and heparin derivatives. 13-C Nuclear-magnetic-resonance analysis and titration data for variously desulphated and periodate-oxidized heparins.", "content": "A heparin derivative that had been O/N-desulphated and re-N-acetylated was investigated by 13C n.m.r. spectroscopy and potentiometric titration. Three forms of uronic acid were observed, tentatively identified as beta-D-glucuronate, and two different forms of alpha-L-iduronate. A comparison of the n.m.r. spectra of heparin, an oligosaccharide (beta-D-glucuronate-2-acetamido-2-deoxy-alpha-D-glucose)n, and heparin that had been subjected to selective oxidation of beta-D-glucuronate, enabled the position of the anomeric carbon of the latter residue to be assigned [delta 102.9 (p.p.m.)]. Periodate oxidation of O/N-desulphated heparin destroyed in addition, approx. 40% of the alpha-L-iduronate content. The remainder of the alpha-L-iduronate residues displayed only one anomeric resonance, at delta 99.7 (p.p.m.). In another preparation, after sequential desulphation of heparin (N-desulphation, re-N-acetylation and O-desulphation) the anomeric resonance of the alpha-L-iduronate residue shifted downfield [from delta99.7 (p.p.m.) to delta 102.3]indicating a change in ring conformation. These data support the interpretation that the unsulphated alpha-L-iduronate residues may adopt two conformations. It was shown that the proportions of alpha-L-iduronate conformers are determined by the sequence of desulphation operations. Also minor components of heparin were assigned.", "contents": "alpha-L-iduronate ring conformations in heparin and heparin derivatives. 13-C Nuclear-magnetic-resonance analysis and titration data for variously desulphated and periodate-oxidized heparins. A heparin derivative that had been O/N-desulphated and re-N-acetylated was investigated by 13C n.m.r. spectroscopy and potentiometric titration. Three forms of uronic acid were observed, tentatively identified as beta-D-glucuronate, and two different forms of alpha-L-iduronate. A comparison of the n.m.r. spectra of heparin, an oligosaccharide (beta-D-glucuronate-2-acetamido-2-deoxy-alpha-D-glucose)n, and heparin that had been subjected to selective oxidation of beta-D-glucuronate, enabled the position of the anomeric carbon of the latter residue to be assigned [delta 102.9 (p.p.m.)]. Periodate oxidation of O/N-desulphated heparin destroyed in addition, approx. 40% of the alpha-L-iduronate content. The remainder of the alpha-L-iduronate residues displayed only one anomeric resonance, at delta 99.7 (p.p.m.). In another preparation, after sequential desulphation of heparin (N-desulphation, re-N-acetylation and O-desulphation) the anomeric resonance of the alpha-L-iduronate residue shifted downfield [from delta99.7 (p.p.m.) to delta 102.3]indicating a change in ring conformation. These data support the interpretation that the unsulphated alpha-L-iduronate residues may adopt two conformations. It was shown that the proportions of alpha-L-iduronate conformers are determined by the sequence of desulphation operations. Also minor components of heparin were assigned."}
{"id": "PMID:216349", "title": "Action of liproprotein lipase on apoprotein-depleted chylomicrons.", "content": "1. Rat lymph chylomicrons were exposed to soluble and to immobilized trypsin. This treatment caused no detectable changes in the chylomicron structure or lipid composition, but did result in virtually total depletion of all their tetramethylurea-soluble apoproteins. 2. The capacity of these apoprotein-depleted chylomicrons to act as substrate for lipoprotein lipase in vitro and in situ (i.e. isolated perfused rat heart) was decreased by about 90 and 75% respectively, compared with intact chylomicrons. 3. On incubation with rat plasma high-density lipoproteins, trypsin-treated chylomicrons readily acquired a full apoprotein complement. This resulted in the complete restoration of their capacity to act as substrate for lipoprotein lipase both in vitro and in situ. 4. It is suggested that with the use of try,sin-treated chylomicrons it is now possible for the first time to investigate the physiological role that individual apoproteins play in the catabolism of triacylglycerol-rich lipoproteins by lipoprotein lipase.", "contents": "Action of liproprotein lipase on apoprotein-depleted chylomicrons. 1. Rat lymph chylomicrons were exposed to soluble and to immobilized trypsin. This treatment caused no detectable changes in the chylomicron structure or lipid composition, but did result in virtually total depletion of all their tetramethylurea-soluble apoproteins. 2. The capacity of these apoprotein-depleted chylomicrons to act as substrate for lipoprotein lipase in vitro and in situ (i.e. isolated perfused rat heart) was decreased by about 90 and 75% respectively, compared with intact chylomicrons. 3. On incubation with rat plasma high-density lipoproteins, trypsin-treated chylomicrons readily acquired a full apoprotein complement. This resulted in the complete restoration of their capacity to act as substrate for lipoprotein lipase both in vitro and in situ. 4. It is suggested that with the use of try,sin-treated chylomicrons it is now possible for the first time to investigate the physiological role that individual apoproteins play in the catabolism of triacylglycerol-rich lipoproteins by lipoprotein lipase."}
{"id": "PMID:216375", "title": "Interaction of Sendai virus with human erythrocytes. IV - Hemolytic factors.", "content": "A study on the composition of structural proteins of Sendai virus deprived of hemolytic activity by pyridine and trypsin in controlled condition was carried out. Pyridine leaves unaffected the electrophoresis pattern of virus proteins; in virus treated with trypsin a drastic reduction of F protein was observed. Researches reported indicate that two factors are required for hemolytic activity of Sendai virus the F protein and the phospholipids of the outer layer of envelope.", "contents": "Interaction of Sendai virus with human erythrocytes. IV - Hemolytic factors. A study on the composition of structural proteins of Sendai virus deprived of hemolytic activity by pyridine and trypsin in controlled condition was carried out. Pyridine leaves unaffected the electrophoresis pattern of virus proteins; in virus treated with trypsin a drastic reduction of F protein was observed. Researches reported indicate that two factors are required for hemolytic activity of Sendai virus the F protein and the phospholipids of the outer layer of envelope."}
{"id": "PMID:216376", "title": "Specific cellular unreactivity during cytomegalovirus infection in man.", "content": "The specific cellular immune response against Cytomegalovirus (CMV) was studied by the Leucocyte Inhibitory Factor (LIF) production test in three groups of subjects: 7 healthy individuals with no CMV antibodies, 4 with antibodies to CMV but without evidence of active infection, and 2 children with clinical CMV infection. Our results show that LIF production in presence of CMV is high in normal seropositive subjects, while it is strongly deficient in patients with active infection, despite a good humoral response to the virus. In one child with congenital infection, a low number of E rosette forming cells was also revealed. We suggest that CMV infection can induce, at least during infancy, a state of specific cellular unresponsiveness to the virus. When the infection is congenital, a generalized depression of the cellular immune system may develop.", "contents": "Specific cellular unreactivity during cytomegalovirus infection in man. The specific cellular immune response against Cytomegalovirus (CMV) was studied by the Leucocyte Inhibitory Factor (LIF) production test in three groups of subjects: 7 healthy individuals with no CMV antibodies, 4 with antibodies to CMV but without evidence of active infection, and 2 children with clinical CMV infection. Our results show that LIF production in presence of CMV is high in normal seropositive subjects, while it is strongly deficient in patients with active infection, despite a good humoral response to the virus. In one child with congenital infection, a low number of E rosette forming cells was also revealed. We suggest that CMV infection can induce, at least during infancy, a state of specific cellular unresponsiveness to the virus. When the infection is congenital, a generalized depression of the cellular immune system may develop."}
{"id": "PMID:216373", "title": "Reactivities of systemic lupus erythematosus sera with cellular and virus antigen preparations.", "content": "Sera of patients with systemic lupus erythematosus (SLE) showed significantly higher complement fixation reactivities with 8 of 10 virus antigen preparations compared to sera of normal subjects, including virus workers, confirming earlier observations. However, one-third of SLE sera were also reactive with cellular antigens, prepared in a manner identical to viral antigens, but from cells not infected with virus. By contrast, only one of 49 normal sera showed reactivity with one of nine cellular antigens, at a minimal titer. Apparently heightened reactivities of SLE sera with virus antigens could be explained in many instances on the basis of reactions with cellular antigens. Serum reactivities with nonviral tissue antigens in SLE must be considered in interpretation of immunologic studies related to viruses and SLE.", "contents": "Reactivities of systemic lupus erythematosus sera with cellular and virus antigen preparations. Sera of patients with systemic lupus erythematosus (SLE) showed significantly higher complement fixation reactivities with 8 of 10 virus antigen preparations compared to sera of normal subjects, including virus workers, confirming earlier observations. However, one-third of SLE sera were also reactive with cellular antigens, prepared in a manner identical to viral antigens, but from cells not infected with virus. By contrast, only one of 49 normal sera showed reactivity with one of nine cellular antigens, at a minimal titer. Apparently heightened reactivities of SLE sera with virus antigens could be explained in many instances on the basis of reactions with cellular antigens. Serum reactivities with nonviral tissue antigens in SLE must be considered in interpretation of immunologic studies related to viruses and SLE."}
{"id": "PMID:216377", "title": "Prevalence of antibody to hepatitis A virus in healthy individuals of Milan.", "content": "We have studied by radioimmunoassay the prevalence of antibody to hepatitis A virus in 436 randomly selected individuals of Milan according to age and sex. Taken together, 70% of subjects provided serological evidence of exposure to HAV. Both sexes resulted similarly immunized (69.7% females and 70.7% males). The anti-HAV prevalence was found to be directly related to age, being on the increase from childhood to adulthood and reaching its peak (9l.5%) in people over fifty. An analysis of the distribution of anti-HAV according to presence or absence of anti-HBs in induviduals under 30 years, revealed that anti-HAV was detectable more frequently in individuals anti-HBs positive than in those without such evidence in sera (71.4% versus 39.7%; P less than 0.01). Finally, 96 sera from children and adolescents of low socioeconomic standard of living were also investigated. In these subjects anti-HAV prevalence was found to be higher than in their counterparts randomly slected from general population.", "contents": "Prevalence of antibody to hepatitis A virus in healthy individuals of Milan. We have studied by radioimmunoassay the prevalence of antibody to hepatitis A virus in 436 randomly selected individuals of Milan according to age and sex. Taken together, 70% of subjects provided serological evidence of exposure to HAV. Both sexes resulted similarly immunized (69.7% females and 70.7% males). The anti-HAV prevalence was found to be directly related to age, being on the increase from childhood to adulthood and reaching its peak (9l.5%) in people over fifty. An analysis of the distribution of anti-HAV according to presence or absence of anti-HBs in induviduals under 30 years, revealed that anti-HAV was detectable more frequently in individuals anti-HBs positive than in those without such evidence in sera (71.4% versus 39.7%; P less than 0.01). Finally, 96 sera from children and adolescents of low socioeconomic standard of living were also investigated. In these subjects anti-HAV prevalence was found to be higher than in their counterparts randomly slected from general population."}
{"id": "PMID:216374", "title": "Search for type-C oncornavirus-related genetic information in tissues from patients with systemic lupus erythematosus.", "content": "Single-stranded 3H-DNA probes complementary to the RNA of Rauscher murine leukemia virus and of simian sarcoma virus were prepared using techniques that permitted complete transcription of the viral genome of each virus. These probes were used in DNA-DNA hybridization studies with the cellular DNA from uncultured specimens of spleens and placentas of patients with systemic lupus erythematosus (SLE). No proviral DNA sequences related to these viruses were detected in these tissues. The results presented here do not support previously reported antigenic data implicating type-C oncornavirus infection of these organs in SLE.", "contents": "Search for type-C oncornavirus-related genetic information in tissues from patients with systemic lupus erythematosus. Single-stranded 3H-DNA probes complementary to the RNA of Rauscher murine leukemia virus and of simian sarcoma virus were prepared using techniques that permitted complete transcription of the viral genome of each virus. These probes were used in DNA-DNA hybridization studies with the cellular DNA from uncultured specimens of spleens and placentas of patients with systemic lupus erythematosus (SLE). No proviral DNA sequences related to these viruses were detected in these tissues. The results presented here do not support previously reported antigenic data implicating type-C oncornavirus infection of these organs in SLE."}
{"id": "PMID:216378", "title": "Seroepidemiologic study of human coronavirus OC43 infections in Italy.", "content": "Human Coronavirus OC43 from suckling mouse brain (SMB) suspension has been adapted to grow in human embryonic lung fibroblast cell cultures. Complement-fixing and hemagglutinating antigens were prepared from infected cell cultures and used in parallel with the same antigens from SMB for a study of the prevalence of OC43 antibody in Northern Italy as well as for the serodiagnosis of recent OC43 infections and reinfections. Results show (i) a higher sensitivity of the hemagglutination-inhibition as compared to the complement fixation test both for antibody detection in seroepidemiological studies and serodiagnosis of acute infections, (ii) a high prevalence of OC43 antibody in Northern Italy, so that only exceptionally are people older than 12 years seronegative, (iii) a high rate of OC43 reinfections during the winter-spring season 1976/77 in a population sample with preexisting antibody (iv) a good quality of reagents prepared from cell cultures, and hence free of contaminating mouse viruses, such as mouse hepatitis virus.", "contents": "Seroepidemiologic study of human coronavirus OC43 infections in Italy. Human Coronavirus OC43 from suckling mouse brain (SMB) suspension has been adapted to grow in human embryonic lung fibroblast cell cultures. Complement-fixing and hemagglutinating antigens were prepared from infected cell cultures and used in parallel with the same antigens from SMB for a study of the prevalence of OC43 antibody in Northern Italy as well as for the serodiagnosis of recent OC43 infections and reinfections. Results show (i) a higher sensitivity of the hemagglutination-inhibition as compared to the complement fixation test both for antibody detection in seroepidemiological studies and serodiagnosis of acute infections, (ii) a high prevalence of OC43 antibody in Northern Italy, so that only exceptionally are people older than 12 years seronegative, (iii) a high rate of OC43 reinfections during the winter-spring season 1976/77 in a population sample with preexisting antibody (iv) a good quality of reagents prepared from cell cultures, and hence free of contaminating mouse viruses, such as mouse hepatitis virus."}
{"id": "PMID:216382", "title": "Pharmacokinetics and pharmacological effects of neostigmine in man.", "content": "1 The pharmacokinetics of neostigmine was studied in six patients during the reversal of neuromuscular block induced by tubocurarine chloride. The effect of the drug on neuromuscular function was simultaneously assessed by electromyography. 2 Neostigmine was rapidly eliminated from plasma after intravenous administration. The decline in the plasma concentration of the drug was invariably resolved into two exponential components. The fast disposition (distribution) half-life of the drug was invariably less than 1 min; the slow disposition (elimination) half-life ranged from 15.4--31.7 min. 3 Neostigmine usually increased the amplitude of the compound muscle action potential and diminished electromyographic decrement within 2 min of intravenous injection. The pharmacological effect of neostigmine was usually maximal between 7 and 15 min. There was an inverse relationship between the plasma concentration of the drug and the facilitation of neuromuscular transmission. 4 Red cell acetylcholinesterase activity was almost completely inhibited within 2--3 min of intravenous injection of neostigmine. Enzyme activity recovered to approximately 28% of control values by 30 min and to 55% by 60 min.", "contents": "Pharmacokinetics and pharmacological effects of neostigmine in man. 1 The pharmacokinetics of neostigmine was studied in six patients during the reversal of neuromuscular block induced by tubocurarine chloride. The effect of the drug on neuromuscular function was simultaneously assessed by electromyography. 2 Neostigmine was rapidly eliminated from plasma after intravenous administration. The decline in the plasma concentration of the drug was invariably resolved into two exponential components. The fast disposition (distribution) half-life of the drug was invariably less than 1 min; the slow disposition (elimination) half-life ranged from 15.4--31.7 min. 3 Neostigmine usually increased the amplitude of the compound muscle action potential and diminished electromyographic decrement within 2 min of intravenous injection. The pharmacological effect of neostigmine was usually maximal between 7 and 15 min. There was an inverse relationship between the plasma concentration of the drug and the facilitation of neuromuscular transmission. 4 Red cell acetylcholinesterase activity was almost completely inhibited within 2--3 min of intravenous injection of neostigmine. Enzyme activity recovered to approximately 28% of control values by 30 min and to 55% by 60 min."}
{"id": "PMID:216383", "title": "Parapoxvirus infections of reindeer and musk ox associated with unusual human infections.", "content": "This report concerns five cases of human infection resulting in lesions morphologically similar to human orf. Parapoxvirus infection in reindeer was the probable source of infection in four cases. The fifth case involved musk ox. Two of the cases involving reindeer are particularly interesting as transmission of infection occurred indirectly. Viral particles were not seen by electron microscopy of human tissues, due probably to the late stage of the illness at the time of examination. However, electron microscopy of negatively stained suspensions prepared from biopsy material collected from reindeer calves at the outbreak of the illness and of post-mortem material from the musk ox revealed characteristic parapoxvirus particles. In one patient the infection was accompanied by fever, lymphadenopathy and nausea, which cleared following a few days of treatment with doxycycline chloride. 4 cases were curetted after 4, 6, 12 and 20 weeks and healed withour scarring whereas the fifth patient was by request left alone. This resulted in localized dark pigmentation following completion of the healing process after 26 weeks.", "contents": "Parapoxvirus infections of reindeer and musk ox associated with unusual human infections. This report concerns five cases of human infection resulting in lesions morphologically similar to human orf. Parapoxvirus infection in reindeer was the probable source of infection in four cases. The fifth case involved musk ox. Two of the cases involving reindeer are particularly interesting as transmission of infection occurred indirectly. Viral particles were not seen by electron microscopy of human tissues, due probably to the late stage of the illness at the time of examination. However, electron microscopy of negatively stained suspensions prepared from biopsy material collected from reindeer calves at the outbreak of the illness and of post-mortem material from the musk ox revealed characteristic parapoxvirus particles. In one patient the infection was accompanied by fever, lymphadenopathy and nausea, which cleared following a few days of treatment with doxycycline chloride. 4 cases were curetted after 4, 6, 12 and 20 weeks and healed withour scarring whereas the fifth patient was by request left alone. This resulted in localized dark pigmentation following completion of the healing process after 26 weeks."}
{"id": "PMID:216384", "title": "Plasma levels of oestrone, oestradiol and gonadotrophins in postmenopausal women after oral and vaginal administration of conjugated equine oestrogens (Premarin).", "content": "Peripheral plasma from five postmenopausal women was analyzed for oestrone and oestradiol during 48 hours after administration of 1.25 mg Premarin (conjugated equine oestrogen) orally and vaginally. Oestrone and oestradiol were separated on columns of Sephadex LH 20 before radioimmunoassay. Administration of 1.25 mg of Premarin produced a marked increase in plasma oestrone levels and 24 hours after treatment the oestrone levels were still above follicular phase levels. The plasma pattern of oestradiol was similar but the elevation was less pronounced. The biological activity of Premarin as indicated by depressed gonadotrophin levels was similar with the intravaginal and oral routes of administration.", "contents": "Plasma levels of oestrone, oestradiol and gonadotrophins in postmenopausal women after oral and vaginal administration of conjugated equine oestrogens (Premarin). Peripheral plasma from five postmenopausal women was analyzed for oestrone and oestradiol during 48 hours after administration of 1.25 mg Premarin (conjugated equine oestrogen) orally and vaginally. Oestrone and oestradiol were separated on columns of Sephadex LH 20 before radioimmunoassay. Administration of 1.25 mg of Premarin produced a marked increase in plasma oestrone levels and 24 hours after treatment the oestrone levels were still above follicular phase levels. The plasma pattern of oestradiol was similar but the elevation was less pronounced. The biological activity of Premarin as indicated by depressed gonadotrophin levels was similar with the intravaginal and oral routes of administration."}
{"id": "PMID:216385", "title": "Failure to suppress adrenal function in congenital adrenal hyperplasia (21-hydroxylase deficiency). Three case reports.", "content": "Three patients, aged 14, 16, and 32 years respectively, with congenital adrenal hyperplasia (21-hydroxylase deficiency) are described. Excessive adrenal activity and ACTH secretion could not be suppressed with doses of corticosteroids sufficient to cause iatrogenic Cushing's syndrome, even though part of the steroid dosage was administered in the late evening. The resistance to feed-back suppression was of the same order as that seen in Cushing's syndrome. Adrenalectomy was performed in the 16-year-old girl, and was followed by a menarche. Adrenalectomy was considered inadvisable in the other two patients.", "contents": "Failure to suppress adrenal function in congenital adrenal hyperplasia (21-hydroxylase deficiency). Three case reports. Three patients, aged 14, 16, and 32 years respectively, with congenital adrenal hyperplasia (21-hydroxylase deficiency) are described. Excessive adrenal activity and ACTH secretion could not be suppressed with doses of corticosteroids sufficient to cause iatrogenic Cushing's syndrome, even though part of the steroid dosage was administered in the late evening. The resistance to feed-back suppression was of the same order as that seen in Cushing's syndrome. Adrenalectomy was performed in the 16-year-old girl, and was followed by a menarche. Adrenalectomy was considered inadvisable in the other two patients."}
{"id": "PMID:216386", "title": "Adenovirus type 21 keratoconjunctivitis.", "content": "A case of keratoconjunctivitis caused by adenovirus type 21 in London has been described. A 59-year-old woman attented hospital in August 1974 complaining of a 3-week history of redness, grittiness, watery discharge, and photophobia in her left eye and a slight upper respiratory infection. Clinical examination showed a moderate follicular conjuctivitis mainly in the lower and upper fornices, which lasted for 6 weeks. In the cornea a moderate amount of epithelial and subepithelial punctate keratitis was observed. The subepithelial opacities were coarse, discrete, and round and lasted for 4 months. The course of follicular conjunctivitis and the subepithelial punctate keratitis in this patient was similar to epidemic keratoconjunctivitis caused by adenovirus 8. A conjunctival swabbing collected from this patient was positive for adenovirus serotype 21.", "contents": "Adenovirus type 21 keratoconjunctivitis. A case of keratoconjunctivitis caused by adenovirus type 21 in London has been described. A 59-year-old woman attented hospital in August 1974 complaining of a 3-week history of redness, grittiness, watery discharge, and photophobia in her left eye and a slight upper respiratory infection. Clinical examination showed a moderate follicular conjuctivitis mainly in the lower and upper fornices, which lasted for 6 weeks. In the cornea a moderate amount of epithelial and subepithelial punctate keratitis was observed. The subepithelial opacities were coarse, discrete, and round and lasted for 4 months. The course of follicular conjunctivitis and the subepithelial punctate keratitis in this patient was similar to epidemic keratoconjunctivitis caused by adenovirus 8. A conjunctival swabbing collected from this patient was positive for adenovirus serotype 21."}
{"id": "PMID:216387", "title": "Inhibition of membrane fusion by suppression of lateral movement of membrane proteins.", "content": "Chicken erythrocytes were fused either by Sendai virus or by the combination of Ca2+ and ionophore A23187. Intramembrane particles and external anionic sites of cells undergoing fusion were found to acquire the ability to undergo a process of cold-induced clustering (thermotropic separation). Cationized ferritin (200 microgram/ml 5% (v/v) cell suspension) inhibited both the fusion process and the thermotropic separation of intramembrane particles and external anionic sites. The correlation between the mobility of membrane proteins and the fusion process is discussed. It is suggest that an increase in the lateral mobility of membrane proteins is a prerequisite for initiation of membrane fusion.", "contents": "Inhibition of membrane fusion by suppression of lateral movement of membrane proteins. Chicken erythrocytes were fused either by Sendai virus or by the combination of Ca2+ and ionophore A23187. Intramembrane particles and external anionic sites of cells undergoing fusion were found to acquire the ability to undergo a process of cold-induced clustering (thermotropic separation). Cationized ferritin (200 microgram/ml 5% (v/v) cell suspension) inhibited both the fusion process and the thermotropic separation of intramembrane particles and external anionic sites. The correlation between the mobility of membrane proteins and the fusion process is discussed. It is suggest that an increase in the lateral mobility of membrane proteins is a prerequisite for initiation of membrane fusion."}
{"id": "PMID:216389", "title": "Streptomycin-induced conformational changes in the 70-S bacterial ribosome.", "content": "Conformational alterations induced by streptomycin in the bacterial ribosome have been investigated using as probes, ethidium bromide, N-[14C]ethylmaleimide and a spin label nitroxide analog of N-ethylmaleimide. 1. The binding of the antibiotic to the ribosome does not affect the reactivity of sulfhydryl groups towards N-ethylmaleimide. 2. The motional freedom of spin labels bound to ribosomal proteins S1 and S18 is increased but it is hardly affected at other labeled sites. This observation suggests that the binding of streptomycin causes a local loosening of the ribosomal structure. 3. Ribosomes are found to bind less ethidium bromide in the presence of streptomycin, which suggests that the binding of streptomycin decreases the degree of organization of ribosomal RNA.", "contents": "Streptomycin-induced conformational changes in the 70-S bacterial ribosome. Conformational alterations induced by streptomycin in the bacterial ribosome have been investigated using as probes, ethidium bromide, N-[14C]ethylmaleimide and a spin label nitroxide analog of N-ethylmaleimide. 1. The binding of the antibiotic to the ribosome does not affect the reactivity of sulfhydryl groups towards N-ethylmaleimide. 2. The motional freedom of spin labels bound to ribosomal proteins S1 and S18 is increased but it is hardly affected at other labeled sites. This observation suggests that the binding of streptomycin causes a local loosening of the ribosomal structure. 3. Ribosomes are found to bind less ethidium bromide in the presence of streptomycin, which suggests that the binding of streptomycin decreases the degree of organization of ribosomal RNA."}
{"id": "PMID:216391", "title": "Non-histone chromatin proteins of B lymphocytes stimulated by lipopolysaccharide. II. Phosphorylation.", "content": "Stimulation of mouse lymphocytes with the B lymphocyte specific mitogen lipopolysaccharide results in an increased rate of phosphorylation of non-histone chromatin proteins. An initial small increase in phosphorylation occurs during the first 2 h and a much larger increase after 24 h of culture with mitogen. The phosphorylated nuclear and cytoplasmic proteins were analysed by polyacrylamide gel electrophoresis and the stimulation index of each prominent peak measured. It was inferred that selective stimulation of the phosphorylation of individual proteins had occurred from: (1) the range of stimulation indices for different proteins, and (2) the appearance, after 8 h stimulation of an apparently newly phosphorylated non-histone chromatin protein of molecular weight 115 000. The pool size of ATP was monitored and showed only small changes during the first 24 h of exposure to lipopolysaccharide. Phosphatase activity was found to be associated with lymphocyte chromatin and nucleoplasm and may help to regulate the level of phosphorylation of non-histone chromatin proteins in vivo. To preserve phosphorylated proteins during their isolation phosphatase activity was inhibited by Na2MoO4. The selective changes in phosphorylation of nuclear proteins precede, and continue during, the stimulation of immunoglobulin and DNA synthesis. Our results are thus consistent with the hypothesis that phosphorylation of non-histone chromatin proteins plays a role in the regulation of gene expression in B lymphocytes.", "contents": "Non-histone chromatin proteins of B lymphocytes stimulated by lipopolysaccharide. II. Phosphorylation. Stimulation of mouse lymphocytes with the B lymphocyte specific mitogen lipopolysaccharide results in an increased rate of phosphorylation of non-histone chromatin proteins. An initial small increase in phosphorylation occurs during the first 2 h and a much larger increase after 24 h of culture with mitogen. The phosphorylated nuclear and cytoplasmic proteins were analysed by polyacrylamide gel electrophoresis and the stimulation index of each prominent peak measured. It was inferred that selective stimulation of the phosphorylation of individual proteins had occurred from: (1) the range of stimulation indices for different proteins, and (2) the appearance, after 8 h stimulation of an apparently newly phosphorylated non-histone chromatin protein of molecular weight 115 000. The pool size of ATP was monitored and showed only small changes during the first 24 h of exposure to lipopolysaccharide. Phosphatase activity was found to be associated with lymphocyte chromatin and nucleoplasm and may help to regulate the level of phosphorylation of non-histone chromatin proteins in vivo. To preserve phosphorylated proteins during their isolation phosphatase activity was inhibited by Na2MoO4. The selective changes in phosphorylation of nuclear proteins precede, and continue during, the stimulation of immunoglobulin and DNA synthesis. Our results are thus consistent with the hypothesis that phosphorylation of non-histone chromatin proteins plays a role in the regulation of gene expression in B lymphocytes."}
{"id": "PMID:216392", "title": "Induction of mitochondrial phosphoenolpyruvate carboxykinase in cultured human fibroblasts.", "content": "Mitochondria of cultured normal human fibroblast cells were found to contain the enzyme phosphoenolpyruvate carboxykinase. The activity of this enzyme in these cells is increased 2- to 3-fold by addition of 5 . 10(-4) M dibutyryl cyclic AMP, or 1.5- to 2-fold by the addition of dexamethasone (2 . 10(-7) M) or hydrocortisone (1.38 . 10(-6) M). These increases in enzyme activity were inhibited cycloheximide and actinomycin D, suggesting they are dependent upon de novo protein synthesis. Cultured human fibroblasts may thus provide a useful system for studying the regulation of mitochondrial phosphoenolpyruvate carboxykinase.", "contents": "Induction of mitochondrial phosphoenolpyruvate carboxykinase in cultured human fibroblasts. Mitochondria of cultured normal human fibroblast cells were found to contain the enzyme phosphoenolpyruvate carboxykinase. The activity of this enzyme in these cells is increased 2- to 3-fold by addition of 5 . 10(-4) M dibutyryl cyclic AMP, or 1.5- to 2-fold by the addition of dexamethasone (2 . 10(-7) M) or hydrocortisone (1.38 . 10(-6) M). These increases in enzyme activity were inhibited cycloheximide and actinomycin D, suggesting they are dependent upon de novo protein synthesis. Cultured human fibroblasts may thus provide a useful system for studying the regulation of mitochondrial phosphoenolpyruvate carboxykinase."}
{"id": "PMID:216393", "title": "Characterization of phosphatidate phosphohydrolase activity associated with isolated lamellar bodies.", "content": "It has been demonstrated that lamellar bodies isolated from porcine lung have L-alpha-phosphatidate phosphohydrolase (EC 3.1.3.4) activity which cannot be accounted for by microsomal or mitochondrial contamination. Phosphatidate phosphohydrolase activity associated with the lamellar bodies is relatively insensitive to Mg2+ and more heat labile than the activity associated with whole lung microsomes. The enzyme was found to be the most active phosphohydrolase present in isolated lamellar bodies and is inhibited by 5 mM Be2+. Lamellar bodies isolated from human and rat lung tissue were also found to have this activity, and the functional role of the enzyme in lamellar bodies is proposed in relation to glycerophospholipid metabolism.", "contents": "Characterization of phosphatidate phosphohydrolase activity associated with isolated lamellar bodies. It has been demonstrated that lamellar bodies isolated from porcine lung have L-alpha-phosphatidate phosphohydrolase (EC 3.1.3.4) activity which cannot be accounted for by microsomal or mitochondrial contamination. Phosphatidate phosphohydrolase activity associated with the lamellar bodies is relatively insensitive to Mg2+ and more heat labile than the activity associated with whole lung microsomes. The enzyme was found to be the most active phosphohydrolase present in isolated lamellar bodies and is inhibited by 5 mM Be2+. Lamellar bodies isolated from human and rat lung tissue were also found to have this activity, and the functional role of the enzyme in lamellar bodies is proposed in relation to glycerophospholipid metabolism."}
{"id": "PMID:216394", "title": "Evidence for the existence of a single enzyme catalyzing the phosphorylation of choline and ethanolamine in primate lung.", "content": "Choline kinase (ATP:choline phosphotransferase, EC 2.7.1.32) has been isolated and purified 1000-fold from adult African Green monkey lung with a yield of 10%. The purified enzyme also phosphorylated ethanolamine (ratio of ethanolamine kinase to choline kinase = 0.30). This ratio remained constant throughout the purification procedure. The Km for choline (3.0 - 10(-5) M) was lower than that of ethanolamine (1.2 - 10(-3) M.) Choline was also found to inhibit ethanolamine kinase activity by 50% at a concentration of 0.005 mM, while ethanolamine inhibited choline only at very high concentrations (100--150 mM). When the enzyme was subjected to inactivation by heat, hemicholinium-3, trypsin digestion, and p-hydroxymercuribenzoate, both ethanolamine kinase and choline kinase activities were destroyed at the same rate. Freezing and thawing in the absence of glycerol also destroyed both activities at the same rate. Based on these findings, we conclude that in adult African Green monkey lung tissue, there is only one enzyme for the phosphorylation of ethanolamine and choline, and that choline phosphorylation predominates.", "contents": "Evidence for the existence of a single enzyme catalyzing the phosphorylation of choline and ethanolamine in primate lung. Choline kinase (ATP:choline phosphotransferase, EC 2.7.1.32) has been isolated and purified 1000-fold from adult African Green monkey lung with a yield of 10%. The purified enzyme also phosphorylated ethanolamine (ratio of ethanolamine kinase to choline kinase = 0.30). This ratio remained constant throughout the purification procedure. The Km for choline (3.0 - 10(-5) M) was lower than that of ethanolamine (1.2 - 10(-3) M.) Choline was also found to inhibit ethanolamine kinase activity by 50% at a concentration of 0.005 mM, while ethanolamine inhibited choline only at very high concentrations (100--150 mM). When the enzyme was subjected to inactivation by heat, hemicholinium-3, trypsin digestion, and p-hydroxymercuribenzoate, both ethanolamine kinase and choline kinase activities were destroyed at the same rate. Freezing and thawing in the absence of glycerol also destroyed both activities at the same rate. Based on these findings, we conclude that in adult African Green monkey lung tissue, there is only one enzyme for the phosphorylation of ethanolamine and choline, and that choline phosphorylation predominates."}
{"id": "PMID:216395", "title": "Heterogeneity in the low density lipoproteins of cholesterol fed African green monkeys (Cercopithecus aethiops).", "content": "The low density lipoproteins of cholesterol-fed African green monkeys were isolated by either preparative ultracentrifugation or agarose column chromatography, then radioiodinated and fractionated by agarose column chromatography. A marked variation was noted in the specific radioactivity of the column fractions regardless of the method used to obtain low density lipoproteins. The radioactivity in each fraction migrated with the beta-globluins, but when the fractions were mixed with carrier plasma, alpha-migrating radioactivity was also detected which was associated with the apo-A-I and apo-C of the high density lipoproteins. The uptake of these apoproteins by the high density lipoproteins reduced the variation in specific radioactivity among the low density lipoprotein fractions. By successive injections of the various 125I-labeled low density lipoprotein fractions into the same recipient, it was also possible to compare the kinetic behavior of the fractions. Large and small low density lipoprotein particles were metabolized differently, indicating that the low density lipoproteins from cholesterol-fed African green monkeys are heterogeneous.", "contents": "Heterogeneity in the low density lipoproteins of cholesterol fed African green monkeys (Cercopithecus aethiops). The low density lipoproteins of cholesterol-fed African green monkeys were isolated by either preparative ultracentrifugation or agarose column chromatography, then radioiodinated and fractionated by agarose column chromatography. A marked variation was noted in the specific radioactivity of the column fractions regardless of the method used to obtain low density lipoproteins. The radioactivity in each fraction migrated with the beta-globluins, but when the fractions were mixed with carrier plasma, alpha-migrating radioactivity was also detected which was associated with the apo-A-I and apo-C of the high density lipoproteins. The uptake of these apoproteins by the high density lipoproteins reduced the variation in specific radioactivity among the low density lipoprotein fractions. By successive injections of the various 125I-labeled low density lipoprotein fractions into the same recipient, it was also possible to compare the kinetic behavior of the fractions. Large and small low density lipoprotein particles were metabolized differently, indicating that the low density lipoproteins from cholesterol-fed African green monkeys are heterogeneous."}
{"id": "PMID:216396", "title": "Comparison of the phospholipase activity of bovine milk lipoprotein lipase against rat plasma very low density and high density lipoprotein.", "content": "The hydrolytic activity of a lipoprotein lipase from bovine milk against triacylglycerol and phosphatidylcholine of rat plasma very low density lipoprotein was determined and compared to that against phosphatidylcholine of high density lipoprotein. 85--90% of the triacylglycerol in very low density lipoprotein were hydrolyzed to fatty acids and 25--35% of the phosphatidylcholine to lysophosphatidylcholine. High density lipoprotein phosphatidylcholine was only minimally susceptible to the enzyme. Even with high amounts of enzyme and prolonged incubation periods, lysophosphatidylcholine generation did not exceed 2--4% of the original amounts of labeled phosphatidylcholine in the high density lipoprotein. We conclude that phospholipids in high density lipoprotein are not substrates for the phospholipase activity of this lipoprotein lipase. These observations suggest that factors other than the presence of apolipoprotein C-II and of glycerophosphatides are of importance for the activity of lipoprotein lipases.", "contents": "Comparison of the phospholipase activity of bovine milk lipoprotein lipase against rat plasma very low density and high density lipoprotein. The hydrolytic activity of a lipoprotein lipase from bovine milk against triacylglycerol and phosphatidylcholine of rat plasma very low density lipoprotein was determined and compared to that against phosphatidylcholine of high density lipoprotein. 85--90% of the triacylglycerol in very low density lipoprotein were hydrolyzed to fatty acids and 25--35% of the phosphatidylcholine to lysophosphatidylcholine. High density lipoprotein phosphatidylcholine was only minimally susceptible to the enzyme. Even with high amounts of enzyme and prolonged incubation periods, lysophosphatidylcholine generation did not exceed 2--4% of the original amounts of labeled phosphatidylcholine in the high density lipoprotein. We conclude that phospholipids in high density lipoprotein are not substrates for the phospholipase activity of this lipoprotein lipase. These observations suggest that factors other than the presence of apolipoprotein C-II and of glycerophosphatides are of importance for the activity of lipoprotein lipases."}
{"id": "PMID:216397", "title": "Beta-oxidation in peroxisomes of brown adipose tissue.", "content": "Peroxisomes and mitochondria from brown adipose tissue of the rat were separated by differential pelleting and isopycnic gradient centrifugation. Both fractions oxidized palmitoyl-CoA with comparable specific activities. Unlike the mitochondrial beta-oxidation the peroxisomal activity was not influenced by carbon monoxide. Peroxisomal beta-oxidation together with carnitine acetyl-transferase, which is also located in peroxisomes, might be involved in chemical thermogenesis by delivering acetyl groups to the mitochondria.", "contents": "Beta-oxidation in peroxisomes of brown adipose tissue. Peroxisomes and mitochondria from brown adipose tissue of the rat were separated by differential pelleting and isopycnic gradient centrifugation. Both fractions oxidized palmitoyl-CoA with comparable specific activities. Unlike the mitochondrial beta-oxidation the peroxisomal activity was not influenced by carbon monoxide. Peroxisomal beta-oxidation together with carnitine acetyl-transferase, which is also located in peroxisomes, might be involved in chemical thermogenesis by delivering acetyl groups to the mitochondria."}
{"id": "PMID:216398", "title": "Electrogenic events in the ubiquinone-cytochrome b/c2 oxidoreductase of Rhodopseudomonas sphaeroides.", "content": "The reductant of ferricytochrome c2 in Rhodopseudomonas sphaeroides is a component, Z, which has an equilibrium oxidation-reduction reaction involving two electrons and two protons with a midpoint potential of 155 mV at pH 7. Under energy coupled conditions, the reduction of ferricytochrome c2 by ZH2 is obligatorily coupled to an apparently electrogenic reaction which is monitored by a red shift of the endogeneous carotenoids. Both ferricytochrome c2 reduction and the associated carotenoid bandshift are similarly affected by the concentrations of ZH2 and ferricytochrome c2, pH, temperature the inhibitors diphenylamine and antimycin, and the presence of ubiquinone. The second-order rate constant for ferricytochrome c2 reduction at pH 7.0 and at 24 degrees C was 2 - 10(9) M-1 - s-1, but this varied with pH, being 5.1 - 10(8) M-1 = s-1 at pH 5.2 and 4.3 - 10(9) M-1 - s-1 at pH 9.3. At pH 7 the reaction had an activation energy of 10.3 kcal/mol.", "contents": "Electrogenic events in the ubiquinone-cytochrome b/c2 oxidoreductase of Rhodopseudomonas sphaeroides. The reductant of ferricytochrome c2 in Rhodopseudomonas sphaeroides is a component, Z, which has an equilibrium oxidation-reduction reaction involving two electrons and two protons with a midpoint potential of 155 mV at pH 7. Under energy coupled conditions, the reduction of ferricytochrome c2 by ZH2 is obligatorily coupled to an apparently electrogenic reaction which is monitored by a red shift of the endogeneous carotenoids. Both ferricytochrome c2 reduction and the associated carotenoid bandshift are similarly affected by the concentrations of ZH2 and ferricytochrome c2, pH, temperature the inhibitors diphenylamine and antimycin, and the presence of ubiquinone. The second-order rate constant for ferricytochrome c2 reduction at pH 7.0 and at 24 degrees C was 2 - 10(9) M-1 - s-1, but this varied with pH, being 5.1 - 10(8) M-1 = s-1 at pH 5.2 and 4.3 - 10(9) M-1 - s-1 at pH 9.3. At pH 7 the reaction had an activation energy of 10.3 kcal/mol."}
{"id": "PMID:216399", "title": "Isolation of photosynthetic catalysts from cyanobacteria.", "content": "Methods are described for the isolation of ferredoxins I and II, cytochrome c-553, cytochrome f, cytochrome c-550 and plastocyanin from large quantities of various cyanobacteria. The amino acid composition of cytochrome c-550 is reported. There is a variation in the relative amounts of these proteins in different batches of cells which may relate to the nutritional status of the organisms.", "contents": "Isolation of photosynthetic catalysts from cyanobacteria. Methods are described for the isolation of ferredoxins I and II, cytochrome c-553, cytochrome f, cytochrome c-550 and plastocyanin from large quantities of various cyanobacteria. The amino acid composition of cytochrome c-550 is reported. There is a variation in the relative amounts of these proteins in different batches of cells which may relate to the nutritional status of the organisms."}
{"id": "PMID:216401", "title": "Studies of the orientation of the mitochondrial redox carriers. III. Orientation of the gx and gy axes of the hemes of cytochrome oxidase with respect to the plane of the membrane in oriented membrane multilayers.", "content": "The EPR absorption properties of the hemes of cytochrome oxidase and their liganded derivatives were examined in oriented multilayers from isolated oxidase, mitochondrial membranes and membrane fragments of a bacterium, Paracoccus denitrificans. The hemes of the oxidase in all the systems investigated were oriented normal to the plane of the multilayers. The directions of the g signals corresponding to the gx and gy axes of the g tensor were found to be different in low-spin ferric heme in fully oxidized oxidase and in half-reduced liganded oxidase. It is suggested that this different orientation of gx and gy in fully oxidized oxidase and half-reduced liganded oxidase arises because the respective EPR signals belong to two different hemes, those of cytochrome a and a3.", "contents": "Studies of the orientation of the mitochondrial redox carriers. III. Orientation of the gx and gy axes of the hemes of cytochrome oxidase with respect to the plane of the membrane in oriented membrane multilayers. The EPR absorption properties of the hemes of cytochrome oxidase and their liganded derivatives were examined in oriented multilayers from isolated oxidase, mitochondrial membranes and membrane fragments of a bacterium, Paracoccus denitrificans. The hemes of the oxidase in all the systems investigated were oriented normal to the plane of the multilayers. The directions of the g signals corresponding to the gx and gy axes of the g tensor were found to be different in low-spin ferric heme in fully oxidized oxidase and in half-reduced liganded oxidase. It is suggested that this different orientation of gx and gy in fully oxidized oxidase and half-reduced liganded oxidase arises because the respective EPR signals belong to two different hemes, those of cytochrome a and a3."}
{"id": "PMID:216402", "title": "On the active transport of organic acids (fluorescein) in the choroid plexus of the rabbit.", "content": "The kinetics of active transport of an organic acid (fluorescein) through the membranes of the choroid plexus from the lateral ventricules of the brain of rabbit was studied both morphologically and functionally. It was shown that fluorescein is actively translocated through the apical and basal membrane of the epithelium and is accumulated in blood capillaries at a concentration exceeding one order of magnitude that in the incubation medium. The kinetic curves displaying saturation and the demonstration of inhibition by other acids shows that a specific carrier is involved in the transfer across the membrane. The active transport of fluorescein at 20 degrees C was found to be sodium independent. Total exclusion of sodium from the incubation medium does not change the Michaelis constant (Km) and maximal velocity (V). The active transport depends on the operation of (Na+ + K+)-ATPase as energy source but obviously no specific complexes with the participation of sodium are involved.", "contents": "On the active transport of organic acids (fluorescein) in the choroid plexus of the rabbit. The kinetics of active transport of an organic acid (fluorescein) through the membranes of the choroid plexus from the lateral ventricules of the brain of rabbit was studied both morphologically and functionally. It was shown that fluorescein is actively translocated through the apical and basal membrane of the epithelium and is accumulated in blood capillaries at a concentration exceeding one order of magnitude that in the incubation medium. The kinetic curves displaying saturation and the demonstration of inhibition by other acids shows that a specific carrier is involved in the transfer across the membrane. The active transport of fluorescein at 20 degrees C was found to be sodium independent. Total exclusion of sodium from the incubation medium does not change the Michaelis constant (Km) and maximal velocity (V). The active transport depends on the operation of (Na+ + K+)-ATPase as energy source but obviously no specific complexes with the participation of sodium are involved."}
{"id": "PMID:216403", "title": "Muscle surface membranes: preparative methods affect apparent chemical properties and neurotoxin binding.", "content": "Considerable disagreement exists between results reported by various authors for lipid composition and enzyme activity in purified muscle membrane fractions presumed to be sarcolemma, although an explanation for these discrepancies has not been presented. We have prepared muscle light surface membrane fractions of comparable density (1.050--1.120) by a low-salt sucrose method and by an LiBr-KCl extraction procedure and compared them for density profile, total lipid and cholesterol content, protein composition and ATPase activity. In addition, sodium channels characteristic of excitable membranes have been quantitated in each preparation using [3H]saxitoxin binding assays, and the density of acetylcholine receptors determined in fractions from control and denervated muscle using alpha-[125I]bungarotoxin. Although both fractions contain predominantly surface membrane, the LiBr fraction consistently shows the higher specific activity of p-nitrophenylphosphatase, higher free cholesterol content, and higher density of sodium channels and acetylcholine receptors. The density distribution of sodium channels appears uniform throughout both fractions. Quantitative differences were seen between sodium dodecyl sulfate polyacrylamide gel electrophoresis patterns of membrane proteins from the two preparations although most bands are represented in both. A majority of the low-salt sucrose light membrane proteins were accessible in varying degrees to labelling with diazotized diiodosulfanylic acid in intact muscle. These results suggest that light surface membrane fractions may be mixtures of sarcolemma and T-tubular membranes. Using our preparative methods, the LiBr fraction may contain predominantly sarcolemma while low-salt sucrose light membranes may be enriched in T-tubular elements.", "contents": "Muscle surface membranes: preparative methods affect apparent chemical properties and neurotoxin binding. Considerable disagreement exists between results reported by various authors for lipid composition and enzyme activity in purified muscle membrane fractions presumed to be sarcolemma, although an explanation for these discrepancies has not been presented. We have prepared muscle light surface membrane fractions of comparable density (1.050--1.120) by a low-salt sucrose method and by an LiBr-KCl extraction procedure and compared them for density profile, total lipid and cholesterol content, protein composition and ATPase activity. In addition, sodium channels characteristic of excitable membranes have been quantitated in each preparation using [3H]saxitoxin binding assays, and the density of acetylcholine receptors determined in fractions from control and denervated muscle using alpha-[125I]bungarotoxin. Although both fractions contain predominantly surface membrane, the LiBr fraction consistently shows the higher specific activity of p-nitrophenylphosphatase, higher free cholesterol content, and higher density of sodium channels and acetylcholine receptors. The density distribution of sodium channels appears uniform throughout both fractions. Quantitative differences were seen between sodium dodecyl sulfate polyacrylamide gel electrophoresis patterns of membrane proteins from the two preparations although most bands are represented in both. A majority of the low-salt sucrose light membrane proteins were accessible in varying degrees to labelling with diazotized diiodosulfanylic acid in intact muscle. These results suggest that light surface membrane fractions may be mixtures of sarcolemma and T-tubular membranes. Using our preparative methods, the LiBr fraction may contain predominantly sarcolemma while low-salt sucrose light membranes may be enriched in T-tubular elements."}
{"id": "PMID:216407", "title": "Metabolism of lipoprotein acylglycerols by liver parenchymal cells.", "content": "We investigated the metabolism by hepatocyte suspensions of the acylglycerols in lipoprotein remnants as well as those associated with albumin and low or high density lipoproteins. Remnants, albumin and plasma lipoproteins, rich in monoacylglycerol were prepared by short-term incubations of radio-labeled chylomicra or very low density lipoproteins with extrahepatic lipoprotein lipase in the presence of albumin and low and high density lipoproteins. We demonstrated that liver parenchymal cells contain an active monoacylglycerol acyltransferase that is located on the extracellular surface of the cell plasma membrane. Further, the enzyme is capable of degrading the monoacylglycerol in all the above forms. Triacylglycerol in intact chylomicra and very low density lipoproteins were not metabolized by the cells to any appreciable degree. The degradation of the remnant triacylglycerol appeared to depend solely on the activity of the lipoprotein lipase bound to the lipoprotein remnants. Little uptake of intact lipoprotein acylglycerols by the hepatocytes was observed; instead, hydrolysis of the substrates in the medium always preceded the uptake of the products. The products were then utilized for the synthesis of triacylglycerol and phospholipid within the cells.", "contents": "Metabolism of lipoprotein acylglycerols by liver parenchymal cells. We investigated the metabolism by hepatocyte suspensions of the acylglycerols in lipoprotein remnants as well as those associated with albumin and low or high density lipoproteins. Remnants, albumin and plasma lipoproteins, rich in monoacylglycerol were prepared by short-term incubations of radio-labeled chylomicra or very low density lipoproteins with extrahepatic lipoprotein lipase in the presence of albumin and low and high density lipoproteins. We demonstrated that liver parenchymal cells contain an active monoacylglycerol acyltransferase that is located on the extracellular surface of the cell plasma membrane. Further, the enzyme is capable of degrading the monoacylglycerol in all the above forms. Triacylglycerol in intact chylomicra and very low density lipoproteins were not metabolized by the cells to any appreciable degree. The degradation of the remnant triacylglycerol appeared to depend solely on the activity of the lipoprotein lipase bound to the lipoprotein remnants. Little uptake of intact lipoprotein acylglycerols by the hepatocytes was observed; instead, hydrolysis of the substrates in the medium always preceded the uptake of the products. The products were then utilized for the synthesis of triacylglycerol and phospholipid within the cells."}
{"id": "PMID:216408", "title": "Effects of betamethasone on phospholipid content, composition and biosynthesis in the fetal rabbit lung.", "content": "Administration of betamethasone (0.2 mg/kg, intramuscularly) to pregnant rabbits had the following effects on the fetal lung at 26--27 days gestation. It increased the amount of phosphatidylcholine in lung lavage by 70% and almost doubled the phosphatidylcholine/sphingomyelin ratio, it increased the rate of incorporation of choline into phosphatidylcholine in fetal lung slices by up to 90%, it increased the activities of pulmonary cholinephosphate cytidylyltransferase and phosphatidate phosphatase by 50% and it reduced the amount of lung glycogen to 60% of the amount in the controls. Betamethasone had no effect on the activities of pulmonary cholinephosphotransferase or lysolecithin: lysolecithin acyltransferase but it slightly decreased the activity of choline kinase. Betamethasone administration to the doe did not increase the amount of surfactant phospholipid in fetal lung lavage to as great an extent as did direct administration of cortisol to the fetuses. Neither did betamethasone stimulate the activity of pulmonary cholinephosphotransferase. These data suggest that agents other than glucocorticoids mediate the stress-induced acceleration of fetal lung maturation and surfactant production.", "contents": "Effects of betamethasone on phospholipid content, composition and biosynthesis in the fetal rabbit lung. Administration of betamethasone (0.2 mg/kg, intramuscularly) to pregnant rabbits had the following effects on the fetal lung at 26--27 days gestation. It increased the amount of phosphatidylcholine in lung lavage by 70% and almost doubled the phosphatidylcholine/sphingomyelin ratio, it increased the rate of incorporation of choline into phosphatidylcholine in fetal lung slices by up to 90%, it increased the activities of pulmonary cholinephosphate cytidylyltransferase and phosphatidate phosphatase by 50% and it reduced the amount of lung glycogen to 60% of the amount in the controls. Betamethasone had no effect on the activities of pulmonary cholinephosphotransferase or lysolecithin: lysolecithin acyltransferase but it slightly decreased the activity of choline kinase. Betamethasone administration to the doe did not increase the amount of surfactant phospholipid in fetal lung lavage to as great an extent as did direct administration of cortisol to the fetuses. Neither did betamethasone stimulate the activity of pulmonary cholinephosphotransferase. These data suggest that agents other than glucocorticoids mediate the stress-induced acceleration of fetal lung maturation and surfactant production."}
{"id": "PMID:216410", "title": "Analysis of electrophoretic behavior of cytochrome c oxidase subunits. Retardation coefficient versus molecular weight in dodecyl sulfate urea gels.", "content": "1. Standard proteins were examined by electrophoresis in highly cross-linked polyacrylamide gels containing sodium dodecyl sulfate and urea. Their behavior was analyzed at a single gel concentration (by molecular weight vs. relative mobility) and at several gel concentrations (molecular weight vs. retardation coefficient). The validity of the latter method of analysis was established for this gel system. 2. Cytochrome c oxidase was subjected to analysis by this method. Compared to standards, subunits I and III showed increased free electrophoretic mobility, while that of subunit V was slightly decreased. The molecular weight values derived were: I, 44 600; II, 22 700; III, 23 500; IV, 16 900; V, 9400; VI, 7600; VII, 4300. The standard errors were all less than +/- 7%. 3. Isolated V and VI were analyzed by two dimensional dodecyl sulfate electrophoresis, in which the second dimension also contained urea. In contrast to their behavior when the holo-enzyme was examined, these isolated subunits V and VI no longer exchange migrating positions relative to each other during the two dimensional analysis. The molecular weight values of the isolated subunits agree with those of the holo-enzyme.", "contents": "Analysis of electrophoretic behavior of cytochrome c oxidase subunits. Retardation coefficient versus molecular weight in dodecyl sulfate urea gels. 1. Standard proteins were examined by electrophoresis in highly cross-linked polyacrylamide gels containing sodium dodecyl sulfate and urea. Their behavior was analyzed at a single gel concentration (by molecular weight vs. relative mobility) and at several gel concentrations (molecular weight vs. retardation coefficient). The validity of the latter method of analysis was established for this gel system. 2. Cytochrome c oxidase was subjected to analysis by this method. Compared to standards, subunits I and III showed increased free electrophoretic mobility, while that of subunit V was slightly decreased. The molecular weight values derived were: I, 44 600; II, 22 700; III, 23 500; IV, 16 900; V, 9400; VI, 7600; VII, 4300. The standard errors were all less than +/- 7%. 3. Isolated V and VI were analyzed by two dimensional dodecyl sulfate electrophoresis, in which the second dimension also contained urea. In contrast to their behavior when the holo-enzyme was examined, these isolated subunits V and VI no longer exchange migrating positions relative to each other during the two dimensional analysis. The molecular weight values of the isolated subunits agree with those of the holo-enzyme."}
{"id": "PMID:216411", "title": "Properties and purification of a glucose-regulated protein from chick embryo fibroblasts.", "content": "A glucose-regulated protein of molecular weight 78,000 (GRP-78) had been purified from a membrane fraction isolated from viral transformed chick embryo fibroblasts. Purification was achieved by extraction of the membrane fraction with Triton X-100, and chromatography on diethylaminoethyl-cellulose and hydroxyapatite. The purified protein exhibited one single spot on two-dimensional polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and has a pI of about 5.3. A monospecific antiserum to GRP-78 was generated in a goat. Immunofluorescence studies using affinity purified antibodies to GRP-78 revealed that this protein was not exposed on the cell surface but was localized in a granular vesicular network inside the cell that resembles the distribution of endoplasmic reticulum. The availability of purified GRP-78 and a specific antiserum to it should prove useful in elucidating the role of this protein in glucose metabolism and its relationship to malignant transformation.", "contents": "Properties and purification of a glucose-regulated protein from chick embryo fibroblasts. A glucose-regulated protein of molecular weight 78,000 (GRP-78) had been purified from a membrane fraction isolated from viral transformed chick embryo fibroblasts. Purification was achieved by extraction of the membrane fraction with Triton X-100, and chromatography on diethylaminoethyl-cellulose and hydroxyapatite. The purified protein exhibited one single spot on two-dimensional polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and has a pI of about 5.3. A monospecific antiserum to GRP-78 was generated in a goat. Immunofluorescence studies using affinity purified antibodies to GRP-78 revealed that this protein was not exposed on the cell surface but was localized in a granular vesicular network inside the cell that resembles the distribution of endoplasmic reticulum. The availability of purified GRP-78 and a specific antiserum to it should prove useful in elucidating the role of this protein in glucose metabolism and its relationship to malignant transformation."}
{"id": "PMID:216414", "title": "Biosynthesis of enterochelin in Escherichia coli K-12: separation of the polypeptides coded for by the entD, E, F and G genes.", "content": "Four enzymic components, coded for by the entD, entE, entF and entG genes, involved in the biosynthesis of enterochelin from 2,3-dihydroxybenzoate have been separated from cell extracts of mutant strains of Escherichia coli K-12. The starting material for fractionation of the E, F and G components was a cell extract of an entD mutant strain, which yielded the E, F and G enzymic components uncontaminated by a functional D component. The D component was isolated from cell extracts of an entE mutant strain. The conversion of 2,3-dihydroxybenzoate and L-serine into enterochelin is dependent on the presence of all four enzymic components. The E and F components were shown to catalyze ATP-pyrophosphate exchange reactions dependent on 2,3-dihydroxybenzoate and L-serine, respectively, whereas fractionated extracts of the entE and entF mutant strains lacked these reactions. These data provide firm evidence that the E and F components are involved in the initial activation of the substrates. The D and G components are necessary for subsequent and, as yet, undefinedd reactions.", "contents": "Biosynthesis of enterochelin in Escherichia coli K-12: separation of the polypeptides coded for by the entD, E, F and G genes. Four enzymic components, coded for by the entD, entE, entF and entG genes, involved in the biosynthesis of enterochelin from 2,3-dihydroxybenzoate have been separated from cell extracts of mutant strains of Escherichia coli K-12. The starting material for fractionation of the E, F and G components was a cell extract of an entD mutant strain, which yielded the E, F and G enzymic components uncontaminated by a functional D component. The D component was isolated from cell extracts of an entE mutant strain. The conversion of 2,3-dihydroxybenzoate and L-serine into enterochelin is dependent on the presence of all four enzymic components. The E and F components were shown to catalyze ATP-pyrophosphate exchange reactions dependent on 2,3-dihydroxybenzoate and L-serine, respectively, whereas fractionated extracts of the entE and entF mutant strains lacked these reactions. These data provide firm evidence that the E and F components are involved in the initial activation of the substrates. The D and G components are necessary for subsequent and, as yet, undefinedd reactions."}
{"id": "PMID:216415", "title": "Regulatory role of cyclic adenosine 3',5'-monophosphate on the platelet cyclooxygenase and platelet function.", "content": "Thromboxane A2 plays an important role in arachidonic acid- and prostaglandin H2-induced platelet aggregation. Agents that stimulate platelet adenylate cyclase (prostaglandin I2, prostaglandin I1 and prostaglandin E1) and dibutyryl cyclic AMP inhibit both thromboxane A2 formation and arachidonate-induced aggregation in platelet-rich plasma. Despite complete suppression of aggregation with agents that elevate cyclic AMP, considerable thromboxane A2 is still formed. Prostaglandin H2-induced aggregations which bypass the cyclooxygenase regulatory step are also inhibited by agents that elevate cyclic AMP without any measurable effect on thromboxane A2 production. These data demonstrate that cyclic AMP can inhibit platelet aggregation by a mechanism independent of its ability to suppress the cyclooxygenase enzyme. Parallel experiments with washed platelet preparations suggest that they may be an inadequate model for studying the relationship between the platelet cyclooxygenase and platelet function.", "contents": "Regulatory role of cyclic adenosine 3',5'-monophosphate on the platelet cyclooxygenase and platelet function. Thromboxane A2 plays an important role in arachidonic acid- and prostaglandin H2-induced platelet aggregation. Agents that stimulate platelet adenylate cyclase (prostaglandin I2, prostaglandin I1 and prostaglandin E1) and dibutyryl cyclic AMP inhibit both thromboxane A2 formation and arachidonate-induced aggregation in platelet-rich plasma. Despite complete suppression of aggregation with agents that elevate cyclic AMP, considerable thromboxane A2 is still formed. Prostaglandin H2-induced aggregations which bypass the cyclooxygenase regulatory step are also inhibited by agents that elevate cyclic AMP without any measurable effect on thromboxane A2 production. These data demonstrate that cyclic AMP can inhibit platelet aggregation by a mechanism independent of its ability to suppress the cyclooxygenase enzyme. Parallel experiments with washed platelet preparations suggest that they may be an inadequate model for studying the relationship between the platelet cyclooxygenase and platelet function."}
{"id": "PMID:216416", "title": "Glucocorticoid modulation of prolactin receptors on mammary cells of lactating mice.", "content": "Prolactin receptors were monitored by measuring 125I-labeled prolactin binding to collagenase-dissociated mammary epithelial cells of lactating BALB/c mice. Specific receptors for iodine-labeled prolactin with an apparent dissociation constant (Kd) of 0.99 . 10(-9) M were present on the dissociated mammary cells. The binding was inhibited by ovine prolactin, human growth hormone and human placental lactogen but not by follicle stimulating hormone, luteinizing hormone, thyroid stimulating hormone, bovine growth hormone or insulin. Adrenal ablation of nursing mothers caused a reduction of the number of prolactin receptors and this effect was preventable by hydrocortisone therapy. Hydrocortisone injections to mothers 3 days after adrenalectomy also induced a replenishment of the prolactin receptors on the mammary cells. Injections of progesterone failed to sustain the high level of mammary cell prolactin receptors in adrenalectomized animals. Stimultaneous injections of hydrocortisone and progesterone to animals 3 days after adrenalectomy caused a partial suppression of the stimulatory action of hydrocortisone alone. The results suggest that hydrocortisone can exert a modulatory influence on mammary cell prolactin receptors in non-hypophysectomized post-partum mice without altering the dissociation constant (Kd) of the receptors.", "contents": "Glucocorticoid modulation of prolactin receptors on mammary cells of lactating mice. Prolactin receptors were monitored by measuring 125I-labeled prolactin binding to collagenase-dissociated mammary epithelial cells of lactating BALB/c mice. Specific receptors for iodine-labeled prolactin with an apparent dissociation constant (Kd) of 0.99 . 10(-9) M were present on the dissociated mammary cells. The binding was inhibited by ovine prolactin, human growth hormone and human placental lactogen but not by follicle stimulating hormone, luteinizing hormone, thyroid stimulating hormone, bovine growth hormone or insulin. Adrenal ablation of nursing mothers caused a reduction of the number of prolactin receptors and this effect was preventable by hydrocortisone therapy. Hydrocortisone injections to mothers 3 days after adrenalectomy also induced a replenishment of the prolactin receptors on the mammary cells. Injections of progesterone failed to sustain the high level of mammary cell prolactin receptors in adrenalectomized animals. Stimultaneous injections of hydrocortisone and progesterone to animals 3 days after adrenalectomy caused a partial suppression of the stimulatory action of hydrocortisone alone. The results suggest that hydrocortisone can exert a modulatory influence on mammary cell prolactin receptors in non-hypophysectomized post-partum mice without altering the dissociation constant (Kd) of the receptors."}
{"id": "PMID:216417", "title": "Identity of mitochondrial and cytosolic glycerate kinases in rat liver and regulation of their intracellular localization by dietary protein.", "content": "Glycerate kinase (ATP: D-glycerate 2-phosphotransferase EC 2.7.1.31) is a key enzyme of glyconeogenesis from serine via hydroxypyruvate. A differential centrifugation of rat liver homogenate and an analysis of the particle fraction by sucrose density gradient centrifugation indicated that 72% and 26% of glycerate kinase are present in mitochondria and cytosol, respectively. A study on the intramitochondrial localization of the enzyme suggested that the mitochondrial glycerate kinase was present in inner membrane and/or matrix. It was found that dietary protein selectively induced mitochondrial glycerate kinase. This result suggested that mitochondrial glycerate kinase had a physiological function for gluconeogenesis from serin. However, the metabolic significance of the cytoplasmic enzyme was still unclear. The properties of solubilized-mitochondrial and cytosolic glycerate kinases were compared. However, no difference between the two enzymes could be found in the kinetic properties, thermal stability, molecular size or electrochemical properties. These results suggested that both enzymes originate from common genetic information. In order to elucidate the regulatory mechanism of the intracellular distribution of glycerate kinase in rat liver, the responses of mitochondrial and cytosolic glycerate kinases to an alteration of dietary protein were studied. The result suggested that an alteration of dietary protein content may regulate the distribution and the translocation of glycerate kinase to mitochondria and cytosol as well as the total amount of glycerate kinase.", "contents": "Identity of mitochondrial and cytosolic glycerate kinases in rat liver and regulation of their intracellular localization by dietary protein. Glycerate kinase (ATP: D-glycerate 2-phosphotransferase EC 2.7.1.31) is a key enzyme of glyconeogenesis from serine via hydroxypyruvate. A differential centrifugation of rat liver homogenate and an analysis of the particle fraction by sucrose density gradient centrifugation indicated that 72% and 26% of glycerate kinase are present in mitochondria and cytosol, respectively. A study on the intramitochondrial localization of the enzyme suggested that the mitochondrial glycerate kinase was present in inner membrane and/or matrix. It was found that dietary protein selectively induced mitochondrial glycerate kinase. This result suggested that mitochondrial glycerate kinase had a physiological function for gluconeogenesis from serin. However, the metabolic significance of the cytoplasmic enzyme was still unclear. The properties of solubilized-mitochondrial and cytosolic glycerate kinases were compared. However, no difference between the two enzymes could be found in the kinetic properties, thermal stability, molecular size or electrochemical properties. These results suggested that both enzymes originate from common genetic information. In order to elucidate the regulatory mechanism of the intracellular distribution of glycerate kinase in rat liver, the responses of mitochondrial and cytosolic glycerate kinases to an alteration of dietary protein were studied. The result suggested that an alteration of dietary protein content may regulate the distribution and the translocation of glycerate kinase to mitochondria and cytosol as well as the total amount of glycerate kinase."}
{"id": "PMID:216418", "title": "Nalpha-trinitrophenyl glucagon: an inhibitor of glucagon-stimulated cyclic AMP production and its effects on glycogenolysis.", "content": "Nalpha-Trinitrophenyl glucagon was prepared by reaction with trinitrobenzene sulfonic acid and purified by ion-exchange chromatography. This derivative has essentially no ability to activate adenylate cyclase from rat liver nor to increase the levels of cyclic AMP in isolated hepatocytes nor to stimulate protein kinase activity. This derivative also can act as a glucagon antagonist with regard to cyclic AMP production and can decrease the degree of stimulation of adenylate cyclase caused by glucagon, as well as lowering the glucagon-stimulated elevation of cyclic AMP levels in intact hepatocytes. Nevertheless, this derivative is capable of activating glycogenolysis in isolated hepatocytes and in augmenting the effect of glucagon on glycogenolysis. This metabolic effect of the glucagon derivative thus appears to occur independent of changes in cyclic AMP levels. These results suggest that glucagon can also activate glycogenolysis by a cyclic AM-independent process.", "contents": "Nalpha-trinitrophenyl glucagon: an inhibitor of glucagon-stimulated cyclic AMP production and its effects on glycogenolysis. Nalpha-Trinitrophenyl glucagon was prepared by reaction with trinitrobenzene sulfonic acid and purified by ion-exchange chromatography. This derivative has essentially no ability to activate adenylate cyclase from rat liver nor to increase the levels of cyclic AMP in isolated hepatocytes nor to stimulate protein kinase activity. This derivative also can act as a glucagon antagonist with regard to cyclic AMP production and can decrease the degree of stimulation of adenylate cyclase caused by glucagon, as well as lowering the glucagon-stimulated elevation of cyclic AMP levels in intact hepatocytes. Nevertheless, this derivative is capable of activating glycogenolysis in isolated hepatocytes and in augmenting the effect of glucagon on glycogenolysis. This metabolic effect of the glucagon derivative thus appears to occur independent of changes in cyclic AMP levels. These results suggest that glucagon can also activate glycogenolysis by a cyclic AM-independent process."}
{"id": "PMID:216422", "title": "Origin and nature of correlations in the Ia feedback pathway of the muscle control system.", "content": "Mammalian primary muscle spindle endings receive two inputs from fusimotor fibres and length changes of their extrafusal environment. Both inputs are also powerful noise sources disturbing the discharge patterns of the receptors. In this paper emphasis is laid on the extrafusal component. It is shown that extrafusal muscle activity can be viewed as a stochastic process which, acting as a common source, can correlate discharge patterns of adjacent muscle spindles. Some quantitative characteristics of these correlations and their relation to the underlying mechanical events are investigated in some detail in order to provide data for more theoretical considerations on their possible physiological importance.", "contents": "Origin and nature of correlations in the Ia feedback pathway of the muscle control system. Mammalian primary muscle spindle endings receive two inputs from fusimotor fibres and length changes of their extrafusal environment. Both inputs are also powerful noise sources disturbing the discharge patterns of the receptors. In this paper emphasis is laid on the extrafusal component. It is shown that extrafusal muscle activity can be viewed as a stochastic process which, acting as a common source, can correlate discharge patterns of adjacent muscle spindles. Some quantitative characteristics of these correlations and their relation to the underlying mechanical events are investigated in some detail in order to provide data for more theoretical considerations on their possible physiological importance."}
{"id": "PMID:216423", "title": "Considerations on mechanisms of focussed signal transmission in the multi-channel muscle stretch reflex system.", "content": "This paper presents theoretical considerations on the possibility of topographically ordered signal transmission in the control system of the muscle stretch reflex. It is investigated how correlations between Ia fibres from primary muscle spindle endings in conjunction with an appropriate connectivity of Ia fibres and motoneurones enable the stretch reflex system to trace local routes through the spinal cord. The complex data processing capabilities of the motoneuronal soma-dendritic membrane system are fully taken into account, and it is argued that correlations between inputs to this system may play an important role for signal transmission through the spinal cord.", "contents": "Considerations on mechanisms of focussed signal transmission in the multi-channel muscle stretch reflex system. This paper presents theoretical considerations on the possibility of topographically ordered signal transmission in the control system of the muscle stretch reflex. It is investigated how correlations between Ia fibres from primary muscle spindle endings in conjunction with an appropriate connectivity of Ia fibres and motoneurones enable the stretch reflex system to trace local routes through the spinal cord. The complex data processing capabilities of the motoneuronal soma-dendritic membrane system are fully taken into account, and it is argued that correlations between inputs to this system may play an important role for signal transmission through the spinal cord."}
{"id": "PMID:216424", "title": "Application of optimal multichannel filtering to simulated nerve signals.", "content": "The optimal linear filters derived in the preceding paper can be thoroughly evaluated using computer simulations, based on the properties of mammalian sensory and motor nerve fibres. Using reasonable values for action potential waveforms, conduction velocity and electrode noise, good separation of motor and sensory signals can be obtained. The performance of the filters is degraded by 1) increasing the electrode noise, 2) introducing dispersion in the conduction velocities, or 3) variation in the waveform of the action potentials from that used in designing the filters. However, the variations needed to seriously degrade performance are quite large compared to those which are likely to be present in mammalian nerves. Use of these filters to distinguish different classes of sensory (or motor) signals based on conduction velocity is discussed.", "contents": "Application of optimal multichannel filtering to simulated nerve signals. The optimal linear filters derived in the preceding paper can be thoroughly evaluated using computer simulations, based on the properties of mammalian sensory and motor nerve fibres. Using reasonable values for action potential waveforms, conduction velocity and electrode noise, good separation of motor and sensory signals can be obtained. The performance of the filters is degraded by 1) increasing the electrode noise, 2) introducing dispersion in the conduction velocities, or 3) variation in the waveform of the action potentials from that used in designing the filters. However, the variations needed to seriously degrade performance are quite large compared to those which are likely to be present in mammalian nerves. Use of these filters to distinguish different classes of sensory (or motor) signals based on conduction velocity is discussed."}
{"id": "PMID:216425", "title": "[Effects of cortisol on lipid and lipoprotein synthesis in rat hepatocytes].", "content": "Under in vivo conditions cortisol induces moderate hyperlipidemia followed by an increase in the phospholipid and triglyceride concentrations in the blood and a decrease of cholesterol; similar changes were observed in the liver. At all time intervals studied cortisol inhibits the phospholipid and cholesterol syntheses and decreases the specific radioactivities of the lipids in the mitochondrial fraction. The hormone has an inhibiting effect on the fatty acid synthesis at early postinjection stages. The phospholipid synthesis is increased after adrenalectomy and is then inhibited after injection of the hormone. A single injection of ACTH or cortisol causes suppression of phospholipid and cholesterol syntheses and a decrease in their specific radioactivities in the mitochondria. A similar effect is observed under stress conditions. In addition, the hormone inhibits the synthesis of lipoprotein apoproteins of very low and high densities. After 5 hours following the hormone injection the lipoprotein apoprotein synthesis in the liver is activated; the activation of apoprotein synthesis is also observed after adrenalectomy. However, the injection of the hormone to adrenalectomized rats decreases the apoprotein synthesis. It was shown that in blood serum cortisol affects the conversions of very low density lipoproteins into low density lipoproteins, thus providing for hyperlipidemia.", "contents": "[Effects of cortisol on lipid and lipoprotein synthesis in rat hepatocytes]. Under in vivo conditions cortisol induces moderate hyperlipidemia followed by an increase in the phospholipid and triglyceride concentrations in the blood and a decrease of cholesterol; similar changes were observed in the liver. At all time intervals studied cortisol inhibits the phospholipid and cholesterol syntheses and decreases the specific radioactivities of the lipids in the mitochondrial fraction. The hormone has an inhibiting effect on the fatty acid synthesis at early postinjection stages. The phospholipid synthesis is increased after adrenalectomy and is then inhibited after injection of the hormone. A single injection of ACTH or cortisol causes suppression of phospholipid and cholesterol syntheses and a decrease in their specific radioactivities in the mitochondria. A similar effect is observed under stress conditions. In addition, the hormone inhibits the synthesis of lipoprotein apoproteins of very low and high densities. After 5 hours following the hormone injection the lipoprotein apoprotein synthesis in the liver is activated; the activation of apoprotein synthesis is also observed after adrenalectomy. However, the injection of the hormone to adrenalectomized rats decreases the apoprotein synthesis. It was shown that in blood serum cortisol affects the conversions of very low density lipoproteins into low density lipoproteins, thus providing for hyperlipidemia."}
{"id": "PMID:216426", "title": "[Different types of interaction of oxidized and reduced cytochrome c with phospholipid vesicles].", "content": "The binding constants of ferri- and ferrocytochrome c interactions with phosphatidylcholine or cardiolipin-containing vesicules were determined. It was found that affinity of ferricytochrome c to phospholipids is one order of magnitude higher that of ferrocytochrome c. A comparative investigation of circular dichroism spectra of free and phospholipid-bound ferri- and ferrocytochrome c was undertaken and it was shown that alpha-helix content of free ferrocytochrome c is higher than that of ferricytochrome c. The formation of ferricytochrome c containing lipoprotein complex led to decrease of alpha-helix content of the protein. In the case of ferrocytochrome c on the other hand interaction with phospholipids did not cause any changes in alpha-helix content. Distribution of ferri- and ferrocytochrome c in different two-phase systems consisting of dextran and polyethylenglycol or dextran and polyethylenglvcol-palmitate was also studied. A comparison of distribution constants shows that higher alpha-helix content of ferrocytochrome c results in the formation of hydrophobic clusters in the protein molecules. In previous communications it was reported that binding of ferrocytochrome c to phospholipids is determined by hydrophobic interactions while in the case of ferricytochrome c the interactions with phospholipids are mainly electrostatic. On the basis of the results obtained in this work it is supposed that it is hydrophobic clusters which determine the binding of ferrocytochrome c to phospholipid membranes.", "contents": "[Different types of interaction of oxidized and reduced cytochrome c with phospholipid vesicles]. The binding constants of ferri- and ferrocytochrome c interactions with phosphatidylcholine or cardiolipin-containing vesicules were determined. It was found that affinity of ferricytochrome c to phospholipids is one order of magnitude higher that of ferrocytochrome c. A comparative investigation of circular dichroism spectra of free and phospholipid-bound ferri- and ferrocytochrome c was undertaken and it was shown that alpha-helix content of free ferrocytochrome c is higher than that of ferricytochrome c. The formation of ferricytochrome c containing lipoprotein complex led to decrease of alpha-helix content of the protein. In the case of ferrocytochrome c on the other hand interaction with phospholipids did not cause any changes in alpha-helix content. Distribution of ferri- and ferrocytochrome c in different two-phase systems consisting of dextran and polyethylenglycol or dextran and polyethylenglvcol-palmitate was also studied. A comparison of distribution constants shows that higher alpha-helix content of ferrocytochrome c results in the formation of hydrophobic clusters in the protein molecules. In previous communications it was reported that binding of ferrocytochrome c to phospholipids is determined by hydrophobic interactions while in the case of ferricytochrome c the interactions with phospholipids are mainly electrostatic. On the basis of the results obtained in this work it is supposed that it is hydrophobic clusters which determine the binding of ferrocytochrome c to phospholipid membranes."}
{"id": "PMID:216427", "title": "[Investigation of the effect of phospholipase on Na,K-ATPase activity].", "content": "Temperature dependence of bovine brain NA,K-ATPase before and after the short-term treatment of enzyme preparations with phospholipases A, C and D is investigated. Arrhenius plots of the temperature dependence of the reaction rate catalysed by Na,K-ATPase are non-linear, they have an inflection at the region of about 20 degrees C. The treatment of the enzyme with phospholipase A makes the inflection more smooth, phospholipase D shifts the inflection by 4 degrees C to lower temperature and simultaneously activates Na,K-ATPase. Phospholipase C sharply changes the Arrhenius curve and makes it linear. The data obtained are discussed with respect to the role of phospholipids in the formation of membrane bilayer and in the regulation of Na,K-ATPase activity.", "contents": "[Investigation of the effect of phospholipase on Na,K-ATPase activity]. Temperature dependence of bovine brain NA,K-ATPase before and after the short-term treatment of enzyme preparations with phospholipases A, C and D is investigated. Arrhenius plots of the temperature dependence of the reaction rate catalysed by Na,K-ATPase are non-linear, they have an inflection at the region of about 20 degrees C. The treatment of the enzyme with phospholipase A makes the inflection more smooth, phospholipase D shifts the inflection by 4 degrees C to lower temperature and simultaneously activates Na,K-ATPase. Phospholipase C sharply changes the Arrhenius curve and makes it linear. The data obtained are discussed with respect to the role of phospholipids in the formation of membrane bilayer and in the regulation of Na,K-ATPase activity."}
{"id": "PMID:216428", "title": "[Properties of sex steroid-binding protein from Xenopus laevis blood serum and detection of an estradiol-binding component in frog liver cytosol which differs from sex steroid-binding protein].", "content": "Binding and physico-chemical properties of sex steroid-binding protein (SBP) from blood serum and those of estrogen-binding components from liver cytosol of pubertal male and female species of clawed frog Xenopus laevis were studied. It was shown that SBP from both sex species of X. laevis specifically binds estradiol (E2) (Ka=5 . 10(6) M-1). Concentration of SBP binding sites for E2 is 7 . 10(-12) mole per mg of protein. Testosterone 5alpha-dihydrotestosterone and E2 effectively compete with [3H]-E2 for SBP binding sites. Hexestrol, progesterone and corticosterone are weak competitors; estrone and E2-17-hemisuccinate do not compete at all. The Strokes radius of SBP is 4.4 nm; sedimentation coefficient is 4.6S. Molecular weight of SBP is 88000; f/f0 is 1.5 SBP from male frog sera has been purified 8.6-fold with 13% yield. Gel-filtration of [3H]-E2 complexes with liver cytosol proteins shows that the livers of male and female frog X. laevis consol proteins shows that the livers of male and female frog X. laevis contain very low amounts of macromolecular component, which specifically binds E2; this component differs from serum SBP in size and in hormonal specificity. It is assumed that this component is a receptor for estrogens.", "contents": "[Properties of sex steroid-binding protein from Xenopus laevis blood serum and detection of an estradiol-binding component in frog liver cytosol which differs from sex steroid-binding protein]. Binding and physico-chemical properties of sex steroid-binding protein (SBP) from blood serum and those of estrogen-binding components from liver cytosol of pubertal male and female species of clawed frog Xenopus laevis were studied. It was shown that SBP from both sex species of X. laevis specifically binds estradiol (E2) (Ka=5 . 10(6) M-1). Concentration of SBP binding sites for E2 is 7 . 10(-12) mole per mg of protein. Testosterone 5alpha-dihydrotestosterone and E2 effectively compete with [3H]-E2 for SBP binding sites. Hexestrol, progesterone and corticosterone are weak competitors; estrone and E2-17-hemisuccinate do not compete at all. The Strokes radius of SBP is 4.4 nm; sedimentation coefficient is 4.6S. Molecular weight of SBP is 88000; f/f0 is 1.5 SBP from male frog sera has been purified 8.6-fold with 13% yield. Gel-filtration of [3H]-E2 complexes with liver cytosol proteins shows that the livers of male and female frog X. laevis consol proteins shows that the livers of male and female frog X. laevis contain very low amounts of macromolecular component, which specifically binds E2; this component differs from serum SBP in size and in hormonal specificity. It is assumed that this component is a receptor for estrogens."}
{"id": "PMID:216429", "title": "Pituitary adrenocortical response to stress during the first day of post-natal life in the rat.", "content": "During the first hours of post-natal life, the newborn rat does not respond to ether stress by a rapid increase of ACTH secretion. Ether inhalation by 5- and 12-hour-old animals slightly but significantly increases plasma and adrenal corticosterone levels, but only 30 min after the onset of stress. At 1 day of age, adrenal response is established. The adrenal cortex of 5-hour-old animals responds normally to an intraperitoneal injection of 25 mU of ACTH. These results indicate that there is an absolute stress non-response period in newborn rats which is followed by a relative stress non-response period. The lack of response is not due to an organic block of the adrenal cortex, but could be due to the accumulation of elevated levels of corticosterone in the central nervous system.", "contents": "Pituitary adrenocortical response to stress during the first day of post-natal life in the rat. During the first hours of post-natal life, the newborn rat does not respond to ether stress by a rapid increase of ACTH secretion. Ether inhalation by 5- and 12-hour-old animals slightly but significantly increases plasma and adrenal corticosterone levels, but only 30 min after the onset of stress. At 1 day of age, adrenal response is established. The adrenal cortex of 5-hour-old animals responds normally to an intraperitoneal injection of 25 mU of ACTH. These results indicate that there is an absolute stress non-response period in newborn rats which is followed by a relative stress non-response period. The lack of response is not due to an organic block of the adrenal cortex, but could be due to the accumulation of elevated levels of corticosterone in the central nervous system."}
{"id": "PMID:216430", "title": "Intra-uterine malnutrition and skeletal retardation.", "content": "In the subgroup of small-for-dates, indicated as intra-uterine malnourished infants, we made an attempt to correlate the degree of starvation and the degree of skeletal retardation. In 31 wasted infants (including 4 post-mature children) and 20 not wasted infants, the ponderal index (100 X W/L3) was determined and deviation from 'normal' calculated. A highly significant correlation was found between the degree of malnutrition (deviation of the ponderal index from normal) and the degree of skeletal retardation (in weeks). The skeletal retardation seems a useful parameter to determine the minimal duration of insufficient energy supply to the fetus.", "contents": "Intra-uterine malnutrition and skeletal retardation. In the subgroup of small-for-dates, indicated as intra-uterine malnourished infants, we made an attempt to correlate the degree of starvation and the degree of skeletal retardation. In 31 wasted infants (including 4 post-mature children) and 20 not wasted infants, the ponderal index (100 X W/L3) was determined and deviation from 'normal' calculated. A highly significant correlation was found between the degree of malnutrition (deviation of the ponderal index from normal) and the degree of skeletal retardation (in weeks). The skeletal retardation seems a useful parameter to determine the minimal duration of insufficient energy supply to the fetus."}
{"id": "PMID:216431", "title": "Studies in meconium in cystic fibrosis: the activities of alpha-D-mannosidase, beta-glucuronidase, beta-D-fucosidase, acid and alkaline phosphatase.", "content": "The specific activities of alpha-D-mannosidase, beta-glucuronidase, beta-D-fucosidase, acid and alkaline phosphatase were studied in meconium from infants with cystic fibrosis (CF) and control subjects. The study revealed significant variations in the specific activity of the enzymes except for acid phosphatase. The variations were not uniform. The activities of alpha-D-mannosidase, beta-glucuronidase and alkaline phosphatase were markedly decreased (p less than 0.001, p less than 0.002, p less than 0.001, respectively), while the activity of beta-D-fucosidase was significantly increased (p less than 0.001) in meconium from the infants with CF. It is suggested that the decreased activity of alpha-D-mannosidase and beta-glucuronidase might contribute to the accumulation of the abnormal substances in CF meconium. The highly increased activity of beta-D-fucosidase raises the possibility of an additional or alternative method for screening newborns for CF using meconium as the test material.", "contents": "Studies in meconium in cystic fibrosis: the activities of alpha-D-mannosidase, beta-glucuronidase, beta-D-fucosidase, acid and alkaline phosphatase. The specific activities of alpha-D-mannosidase, beta-glucuronidase, beta-D-fucosidase, acid and alkaline phosphatase were studied in meconium from infants with cystic fibrosis (CF) and control subjects. The study revealed significant variations in the specific activity of the enzymes except for acid phosphatase. The variations were not uniform. The activities of alpha-D-mannosidase, beta-glucuronidase and alkaline phosphatase were markedly decreased (p less than 0.001, p less than 0.002, p less than 0.001, respectively), while the activity of beta-D-fucosidase was significantly increased (p less than 0.001) in meconium from the infants with CF. It is suggested that the decreased activity of alpha-D-mannosidase and beta-glucuronidase might contribute to the accumulation of the abnormal substances in CF meconium. The highly increased activity of beta-D-fucosidase raises the possibility of an additional or alternative method for screening newborns for CF using meconium as the test material."}
{"id": "PMID:216432", "title": "The binding of 125I-TSH to thyroid cell receptors previously deformed (in neonatal age) by gonadotropin treatment.", "content": "Single gonadotropin treatment of newborn rats caused a 63-71% decrease of TSH-binding on isolated thyroid cells prepared from thyroid glands of both 6- and 13-month-old animals. This fact points out that: (1) in newborn animals the hormone receptors are still plastic and deformable and (2) the damaging effect of the analogous hormone manifests itself at the receptor level.", "contents": "The binding of 125I-TSH to thyroid cell receptors previously deformed (in neonatal age) by gonadotropin treatment. Single gonadotropin treatment of newborn rats caused a 63-71% decrease of TSH-binding on isolated thyroid cells prepared from thyroid glands of both 6- and 13-month-old animals. This fact points out that: (1) in newborn animals the hormone receptors are still plastic and deformable and (2) the damaging effect of the analogous hormone manifests itself at the receptor level."}
{"id": "PMID:216433", "title": "The hypotriglyceridemic effect of chenodeoxycholic acid in type IV hyperlipemia.", "content": "The effect of chenodeoxycholic acid on the fasting serum triglycerides was studied in 30 patients with type IV hyperlipemia and in 20 patients with primary gout and associated endogenous hypertriglyceridemia, the triglycerides being determined before treatment and at monthly intervals for three months. Chenodeoxycholic acid treatment resulted in a significant lowering of the serum triglycerides in both groups of patients. The drug was well tolerated and there were no undesirable side-effects. Although the mechanism of action is still not known, the drug is thought to reduce triglyceride synthesis in the liver. Chenodeoxycholic acid appears to be electively indicated in type IV hyperlipemia treatment.", "contents": "The hypotriglyceridemic effect of chenodeoxycholic acid in type IV hyperlipemia. The effect of chenodeoxycholic acid on the fasting serum triglycerides was studied in 30 patients with type IV hyperlipemia and in 20 patients with primary gout and associated endogenous hypertriglyceridemia, the triglycerides being determined before treatment and at monthly intervals for three months. Chenodeoxycholic acid treatment resulted in a significant lowering of the serum triglycerides in both groups of patients. The drug was well tolerated and there were no undesirable side-effects. Although the mechanism of action is still not known, the drug is thought to reduce triglyceride synthesis in the liver. Chenodeoxycholic acid appears to be electively indicated in type IV hyperlipemia treatment."}
{"id": "PMID:216434", "title": "In vitro interaction of LDL, anti-lipoprotein IgA and human fibroblasts.", "content": "Human LDL were bound and internalized by cultured human fibroblasts. When an antilipoprotein IgA kappa from a case of myeloma with hyperlipidemia and xanthomatosis was introduced into the system, LDL uptake dropped by 50% but LDL binding to fibroblasts was unchanged. In the same system, IgG and IgA controls were inactive.", "contents": "In vitro interaction of LDL, anti-lipoprotein IgA and human fibroblasts. Human LDL were bound and internalized by cultured human fibroblasts. When an antilipoprotein IgA kappa from a case of myeloma with hyperlipidemia and xanthomatosis was introduced into the system, LDL uptake dropped by 50% but LDL binding to fibroblasts was unchanged. In the same system, IgG and IgA controls were inactive."}
{"id": "PMID:216435", "title": "[Thermal sensitivity of enzymes in trisomy 21 leukocytes].", "content": "Thermosensitivity of glucose 6-phosphate dehydrogenase and myloperoxidase was investigated in the leukocyte lysates from patients with Down's syndrome. A statistically significant enhancement of thermosensitivity of both the enzymes investigated was revealed in the aberrant cells in comparison with the control. The noted differences can be based on the increased incidence of mutation injuries in the aberrant cells, as well as on anomalous postranslational modification of the protein molecules.", "contents": "[Thermal sensitivity of enzymes in trisomy 21 leukocytes]. Thermosensitivity of glucose 6-phosphate dehydrogenase and myloperoxidase was investigated in the leukocyte lysates from patients with Down's syndrome. A statistically significant enhancement of thermosensitivity of both the enzymes investigated was revealed in the aberrant cells in comparison with the control. The noted differences can be based on the increased incidence of mutation injuries in the aberrant cells, as well as on anomalous postranslational modification of the protein molecules."}
{"id": "PMID:216438", "title": "Hereditary myeloperoxidase deficiency.", "content": "The functional properties of granulocytes in a diabetic patient deficient in myeloperoxidase (MPO) were compared with those of granulocytes in healthy subjects. The granulocytes of this patient had normal phagocytic activity. The microbicidal activity of the granulocytes was partially diminished with regard to Staphylococcus aureus and was almost nil with regard to Candida albicans. Fungicidal activity of normal granulocytes was shown to be impaired during the in vitro artificial hyperglycemic condition. The relationship among diabetes mellitus, MPO deficiency, and serious C. albicans infection was examined. Genetic investigation was carried out in 28 members of the proband's family. In close relatives of the patient, MPO values were found to be diminshed to a greater or lesser degree, thus suggesting variable expressivity of the heterozygote state of MPO deficiency.", "contents": "Hereditary myeloperoxidase deficiency. The functional properties of granulocytes in a diabetic patient deficient in myeloperoxidase (MPO) were compared with those of granulocytes in healthy subjects. The granulocytes of this patient had normal phagocytic activity. The microbicidal activity of the granulocytes was partially diminished with regard to Staphylococcus aureus and was almost nil with regard to Candida albicans. Fungicidal activity of normal granulocytes was shown to be impaired during the in vitro artificial hyperglycemic condition. The relationship among diabetes mellitus, MPO deficiency, and serious C. albicans infection was examined. Genetic investigation was carried out in 28 members of the proband's family. In close relatives of the patient, MPO values were found to be diminshed to a greater or lesser degree, thus suggesting variable expressivity of the heterozygote state of MPO deficiency."}
{"id": "PMID:216439", "title": "Action of thrombin on surface glycoproteins of human platelets.", "content": "We labeled surface glycoproteins of human platelets by the neuraminidase-galactose oxidase/borotritiide and the periodate/borotritiide methods. When labeled platelets were treated with 1-nM thrombin, a minor glycoprotein weighing 68,000-85,000-d was lost from the surface, and a soluble glycoprotein weighing 57,000-68,000-d was found in the supernatant. Treatment of platelets with ADP, collagen, or the calcium ionophore A23187 did not cause loss of the 68,000-85,000-d glycoprotein from platelet surfaces or appearance of the 57,000-68,000-d glycoprotein in the supernatant. However, trace amounts of the intact 68,000-85,000-d glycoprotein were found in the supernatants of platelets that were not treated with thrombin. The numerous effects of thrombin on platelets could be initiated by cleavage and release the thrombin-sensitive glycoprotein.", "contents": "Action of thrombin on surface glycoproteins of human platelets. We labeled surface glycoproteins of human platelets by the neuraminidase-galactose oxidase/borotritiide and the periodate/borotritiide methods. When labeled platelets were treated with 1-nM thrombin, a minor glycoprotein weighing 68,000-85,000-d was lost from the surface, and a soluble glycoprotein weighing 57,000-68,000-d was found in the supernatant. Treatment of platelets with ADP, collagen, or the calcium ionophore A23187 did not cause loss of the 68,000-85,000-d glycoprotein from platelet surfaces or appearance of the 57,000-68,000-d glycoprotein in the supernatant. However, trace amounts of the intact 68,000-85,000-d glycoprotein were found in the supernatants of platelets that were not treated with thrombin. The numerous effects of thrombin on platelets could be initiated by cleavage and release the thrombin-sensitive glycoprotein."}
{"id": "PMID:216440", "title": "In vitro platelet abnormality in adenosine deaminase deficiency and severe combined immunodeficiency.", "content": "The platelets of an infant with severe combined immune deficiency and adenosine deaminase deficiency showed markedly diminished responses to ADP-induced aggregation in vitro. This abnormality was corrected by the addition of purified adenosine deaminase in vitro. Exogenous adenosine added to platelet-rich plasma caused markedly prolonged inhibition of ADP-induced aggregation. This was shown by isotopic studies to be due to slow clearance of adenosine and hence persistence of this nucleoside. Direct assay for adenosine deaminiase in plasma and platelet lysates of the patient confirmed the very low activity of this enzyme. Raised cAMP levels were demonstrated in his platelets. The deranged adenosine metabolism and raised cAMP in the platelets of this child with severe combined immunodeficiency may explain the altered response to ADP. Despite the in vitro platelet aggregation abnormality, the patient had no clinical evidence of impaired hemostasis.", "contents": "In vitro platelet abnormality in adenosine deaminase deficiency and severe combined immunodeficiency. The platelets of an infant with severe combined immune deficiency and adenosine deaminase deficiency showed markedly diminished responses to ADP-induced aggregation in vitro. This abnormality was corrected by the addition of purified adenosine deaminase in vitro. Exogenous adenosine added to platelet-rich plasma caused markedly prolonged inhibition of ADP-induced aggregation. This was shown by isotopic studies to be due to slow clearance of adenosine and hence persistence of this nucleoside. Direct assay for adenosine deaminiase in plasma and platelet lysates of the patient confirmed the very low activity of this enzyme. Raised cAMP levels were demonstrated in his platelets. The deranged adenosine metabolism and raised cAMP in the platelets of this child with severe combined immunodeficiency may explain the altered response to ADP. Despite the in vitro platelet aggregation abnormality, the patient had no clinical evidence of impaired hemostasis."}
{"id": "PMID:216441", "title": "Alterations in lysosomes, catalase-containing organelles, mitochondria and plasma membrane fragments from hypertensive rat aorta and caudal artery.", "content": "Vascular smooth muscle (VSM) cells from hypertensive and normotensive rat aortae and caudal arteries were isolated by enzymatic techniques, homogenized, and fractionated by differential pelleting. By these techniques, only mitochondria could be enriched more than fivefold in any one fraction. The other organelles were distributed heterogeneously in almost all fractions. Hypertensive smooth muscle enzyme distribution patterns were different from the normotensive, suggesting that changes in sedimentation characteristics had occurred. Activity of the enzyme 5'-nucleotidase increased in whole tissue homogenates and in the 'microsomal' fraction of aortic and caudal artery of hypertensive VSM. The lysosomal protease, cathepsin D, of hypertensive animals decreased in activity for both vascular smooth muscles while N-acetyl-beta-glucosaminidase and pNPPase (acid phosphatase) increased. The possibility of a functional deficiency in protein degradation causing lysosomal overloading is discussed.", "contents": "Alterations in lysosomes, catalase-containing organelles, mitochondria and plasma membrane fragments from hypertensive rat aorta and caudal artery. Vascular smooth muscle (VSM) cells from hypertensive and normotensive rat aortae and caudal arteries were isolated by enzymatic techniques, homogenized, and fractionated by differential pelleting. By these techniques, only mitochondria could be enriched more than fivefold in any one fraction. The other organelles were distributed heterogeneously in almost all fractions. Hypertensive smooth muscle enzyme distribution patterns were different from the normotensive, suggesting that changes in sedimentation characteristics had occurred. Activity of the enzyme 5'-nucleotidase increased in whole tissue homogenates and in the 'microsomal' fraction of aortic and caudal artery of hypertensive VSM. The lysosomal protease, cathepsin D, of hypertensive animals decreased in activity for both vascular smooth muscles while N-acetyl-beta-glucosaminidase and pNPPase (acid phosphatase) increased. The possibility of a functional deficiency in protein degradation causing lysosomal overloading is discussed."}
{"id": "PMID:216442", "title": "Platelet adherence in endothelial cell cultures.", "content": "Platelet adherence in bovine endothelial cultures was studied by scanning and transmission electron microscopy. Following incubation with platelet-rich plasma (PRP), platelet adherence to endothelial cell surfaces was rare as compared to similarly-tested fibroblasts which displayed numerous adherent platelets. When endothelial cells were induced to retract from their substrate by exposure to cold or versene and then incubated with PRP, platelets were observed adhering to endothelial cell processes and to an extracellular microfilamentous network, located beneath the cell. Platelets were attached singly, retained their discoidal shape, and showed no evidence of granule release. In contrast, microfilaments and adherent platelets were conspicuously absent in endothelial cultures which were retracted with trypsin or collagenase and incubated with PRP. These preliminary results suggest that the observed interaction between platelets and the subcellular surface of cultured endothelial cells is specific for an extracellular network of microfilaments produced by the cells.", "contents": "Platelet adherence in endothelial cell cultures. Platelet adherence in bovine endothelial cultures was studied by scanning and transmission electron microscopy. Following incubation with platelet-rich plasma (PRP), platelet adherence to endothelial cell surfaces was rare as compared to similarly-tested fibroblasts which displayed numerous adherent platelets. When endothelial cells were induced to retract from their substrate by exposure to cold or versene and then incubated with PRP, platelets were observed adhering to endothelial cell processes and to an extracellular microfilamentous network, located beneath the cell. Platelets were attached singly, retained their discoidal shape, and showed no evidence of granule release. In contrast, microfilaments and adherent platelets were conspicuously absent in endothelial cultures which were retracted with trypsin or collagenase and incubated with PRP. These preliminary results suggest that the observed interaction between platelets and the subcellular surface of cultured endothelial cells is specific for an extracellular network of microfilaments produced by the cells."}
{"id": "PMID:216444", "title": "Acupuncture in narcotic withdrawal: a preliminary report on biochemical changes in the blood and urine of heroin addicts.", "content": "Eight female heroin-addicted subjects were treated over a 10-day period by acupuncture and electrical stimulation (AES). Their plasma ACTH, cortisol and c-AMP levels were reduced after initial AES treatment. The reduction of c-AMP was significant the most of the three. The suppression of these compounds may be associated with the temporary relief of withdrawl symptoms on and after each AES treatment in the first three days. On the third day, ACTH, cortisol and c-AMP levels did not show significant changes after AES. This was presumably due to the disappearance of withdrawal symptoms and possibly to the stabilizing effect of the treatment. Both the ACTH and c-AMP levels were generally lower at the end of the treatment period. Results of the present investigation suggest that plasma c-AMP may be the best parameter by which to gauge the response of heroin addicts to AES.", "contents": "Acupuncture in narcotic withdrawal: a preliminary report on biochemical changes in the blood and urine of heroin addicts. Eight female heroin-addicted subjects were treated over a 10-day period by acupuncture and electrical stimulation (AES). Their plasma ACTH, cortisol and c-AMP levels were reduced after initial AES treatment. The reduction of c-AMP was significant the most of the three. The suppression of these compounds may be associated with the temporary relief of withdrawl symptoms on and after each AES treatment in the first three days. On the third day, ACTH, cortisol and c-AMP levels did not show significant changes after AES. This was presumably due to the disappearance of withdrawal symptoms and possibly to the stabilizing effect of the treatment. Both the ACTH and c-AMP levels were generally lower at the end of the treatment period. Results of the present investigation suggest that plasma c-AMP may be the best parameter by which to gauge the response of heroin addicts to AES."}
{"id": "PMID:216447", "title": "The effects of opiate receptor agonists and antagonists on the stress-induced secretion of corticosterone in mice.", "content": "1 Intraperitoneal administration of normorphine, morphine or naloxone or exposure to ether vapour for 1 min, elevated plasma corticosteroid concentrations in mice. 2 Injection of saline or exposure to ether vapour rendered mice less sensitive to a subsequent exposure to ether vapour 15 min later. 3 Treatment with normorphine (50 mg/kg) potentiated the corticosteroid response to ether stress whilst pentazocine (20 mg/kg), naltrexone (10 mg/kg), morphine (24 mg/kg), levorphanol (20 mg/kg) and naloxone (50 mg/kg) prevented the stress-induced elevation of plasma corticosteroids. 4 Both naloxone and morphine inhibited the potentiation by normorphine of the response to ether, the dose of naloxone required being higher than that for inhibition of normorphine analgesia. 5 It is concluded that endogenous opioid peptides may be involved in the control of the response to ether stress in mice.", "contents": "The effects of opiate receptor agonists and antagonists on the stress-induced secretion of corticosterone in mice. 1 Intraperitoneal administration of normorphine, morphine or naloxone or exposure to ether vapour for 1 min, elevated plasma corticosteroid concentrations in mice. 2 Injection of saline or exposure to ether vapour rendered mice less sensitive to a subsequent exposure to ether vapour 15 min later. 3 Treatment with normorphine (50 mg/kg) potentiated the corticosteroid response to ether stress whilst pentazocine (20 mg/kg), naltrexone (10 mg/kg), morphine (24 mg/kg), levorphanol (20 mg/kg) and naloxone (50 mg/kg) prevented the stress-induced elevation of plasma corticosteroids. 4 Both naloxone and morphine inhibited the potentiation by normorphine of the response to ether, the dose of naloxone required being higher than that for inhibition of normorphine analgesia. 5 It is concluded that endogenous opioid peptides may be involved in the control of the response to ether stress in mice."}
{"id": "PMID:216448", "title": "N-Aralkyl substitution increases the affinity of adrenergic drugs for the alpha-adrenoceptor in rat liver.", "content": "1 The alpha-adrenoceptor of rat liver plasma membranes was studied by use of the specific alpha-antagonist [3H]-dihydroergocryptine ([3H]-DHEC). Catecholamines and adrenergic compounds displayed an order of affinity that is typical of an alpha-receptor. Nevertheless, protokylol, a potent beta-adrenoceptor agonist, exhibited a higher affinity than that of adrenaline for alpha-sites. This result might be due to its bulky substituent on the amino group. 2 Further displacement experiments between [3H]-DHEC and four pairs of drugs differently substituted on the amino group (isoprenaline vs Cc-25, orciprenaline vs fenoterol, AH 3474 vs labetalol, pindolol vs hydroxybenzylpindolol) provided evidence that N-alkyl substitution decreased the affinity for alpha-sites (20 micromolar less than KD less than 200 micromolar), whereas an N-aralkyl one increased the affinity (0.17 micromloar less than KD less than 4.6 micromolar). 3 It is concluded that a substitution on the amino group by a bulky, hydrophobic moiety enhances the affinity of drugs for the alpha-adrenoceptors.", "contents": "N-Aralkyl substitution increases the affinity of adrenergic drugs for the alpha-adrenoceptor in rat liver. 1 The alpha-adrenoceptor of rat liver plasma membranes was studied by use of the specific alpha-antagonist [3H]-dihydroergocryptine ([3H]-DHEC). Catecholamines and adrenergic compounds displayed an order of affinity that is typical of an alpha-receptor. Nevertheless, protokylol, a potent beta-adrenoceptor agonist, exhibited a higher affinity than that of adrenaline for alpha-sites. This result might be due to its bulky substituent on the amino group. 2 Further displacement experiments between [3H]-DHEC and four pairs of drugs differently substituted on the amino group (isoprenaline vs Cc-25, orciprenaline vs fenoterol, AH 3474 vs labetalol, pindolol vs hydroxybenzylpindolol) provided evidence that N-alkyl substitution decreased the affinity for alpha-sites (20 micromolar less than KD less than 200 micromolar), whereas an N-aralkyl one increased the affinity (0.17 micromloar less than KD less than 4.6 micromolar). 3 It is concluded that a substitution on the amino group by a bulky, hydrophobic moiety enhances the affinity of drugs for the alpha-adrenoceptors."}
{"id": "PMID:216449", "title": "Calcium requirements for electrically-induced release of an endogenous opiate receptor ligand from the guinea-pig ileum.", "content": "Calcium requirements for electrically-induced release of an endogenous opiate receptor ligand in the myenteric plexus-longitudinal muscle strip of the guinea-pig ileum were studied. The naloxone-reversible depression of the electrically evoked contraction caused by stimulation at 10 Hz in normal Krebs solution was markedly reduced by decreasing the calcium concentration in the solution. The depression was greatly diminished by increasing the magnesium concentration in the solution. These results show that the electrically-induced release of an opiate-like material requires calcium ions.", "contents": "Calcium requirements for electrically-induced release of an endogenous opiate receptor ligand from the guinea-pig ileum. Calcium requirements for electrically-induced release of an endogenous opiate receptor ligand in the myenteric plexus-longitudinal muscle strip of the guinea-pig ileum were studied. The naloxone-reversible depression of the electrically evoked contraction caused by stimulation at 10 Hz in normal Krebs solution was markedly reduced by decreasing the calcium concentration in the solution. The depression was greatly diminished by increasing the magnesium concentration in the solution. These results show that the electrically-induced release of an opiate-like material requires calcium ions."}
{"id": "PMID:216450", "title": "A comparison of the facilitatory actions of 4-aminopyridine methiodide and 4-aminopyridine on neuromuscular transmission.", "content": "1 4-Aminopyridine methiodide (4-APMI), a quaternary analogue of aminopyridine (4-AP), was tested for neuromuscular facilitatory actions on the chick biventer cervicis and frog sartorius nerve-muscle preparations. 2 In the chick, 4-APMI (10(-4) to 10(-2) M) augmented indirectly elicited twitches and reversed tubocurarine-induced neuromuscular block. Reversal of tubocurarine block was observed after treatment of the muscle with an anticholinesterase. 4-APMI did not itself produce contracture but augmented responses to added acetylcholine. 3 4-APMI (10(-4) M) prolonged the time courses of endplate potentials (e.p.ps) and miniature endplate potentials (m.e.p.ps) in the frog. 4 4-APMI (10(-4) M) increased e.p.p. quantal content. 4-AP was about 100 times more active than 4-APMI in increasing quantal content. Both compounds prolonged muscle action potentials at similar concentrations. 5 4-APMI (10(-3) to 3 X 10(-3) M) possessed anticholinesterase activity in homogenates of chick biventer cervicis muscle. 6 It is concluded that 4-APMI increases evoked acetylcholine release and also possesses a weak anticholinesterase action. The greater action of 4-AP on quantal content is probably due to an intracellular action, possibly involving the release of calcium ions.", "contents": "A comparison of the facilitatory actions of 4-aminopyridine methiodide and 4-aminopyridine on neuromuscular transmission. 1 4-Aminopyridine methiodide (4-APMI), a quaternary analogue of aminopyridine (4-AP), was tested for neuromuscular facilitatory actions on the chick biventer cervicis and frog sartorius nerve-muscle preparations. 2 In the chick, 4-APMI (10(-4) to 10(-2) M) augmented indirectly elicited twitches and reversed tubocurarine-induced neuromuscular block. Reversal of tubocurarine block was observed after treatment of the muscle with an anticholinesterase. 4-APMI did not itself produce contracture but augmented responses to added acetylcholine. 3 4-APMI (10(-4) M) prolonged the time courses of endplate potentials (e.p.ps) and miniature endplate potentials (m.e.p.ps) in the frog. 4 4-APMI (10(-4) M) increased e.p.p. quantal content. 4-AP was about 100 times more active than 4-APMI in increasing quantal content. Both compounds prolonged muscle action potentials at similar concentrations. 5 4-APMI (10(-3) to 3 X 10(-3) M) possessed anticholinesterase activity in homogenates of chick biventer cervicis muscle. 6 It is concluded that 4-APMI increases evoked acetylcholine release and also possesses a weak anticholinesterase action. The greater action of 4-AP on quantal content is probably due to an intracellular action, possibly involving the release of calcium ions."}
{"id": "PMID:216451", "title": "Cyclic adenosine 3', 5'-monophosphate and the mechanism of action of three common anti-inflammatory drugs.", "content": "1 The effects of indomethacin, dexamethasone and colchicine on cyclic adenosine 3', 5'-monophosphate (cyclic AMP) concentration in leucocytes during a crystal-induced pleurisy in rats were studied. 2 Each of the drugs significantly increased leucocyte cyclic AMP content within 3 h of the injection of crystals. 3 By 6 h, leucocyte cyclic AMP levels returning toward control levels and could not be sustained at the higher level by an additional administration of the respective anti-inflammatory drug.", "contents": "Cyclic adenosine 3', 5'-monophosphate and the mechanism of action of three common anti-inflammatory drugs. 1 The effects of indomethacin, dexamethasone and colchicine on cyclic adenosine 3', 5'-monophosphate (cyclic AMP) concentration in leucocytes during a crystal-induced pleurisy in rats were studied. 2 Each of the drugs significantly increased leucocyte cyclic AMP content within 3 h of the injection of crystals. 3 By 6 h, leucocyte cyclic AMP levels returning toward control levels and could not be sustained at the higher level by an additional administration of the respective anti-inflammatory drug."}
{"id": "PMID:216452", "title": "alpha And beta-adrenoceptors in the detrusor muscle and bladder base of the pig and beta-adrenoceptors in the detrusor muscle of man.", "content": "1 The presence and type of adrenoceptors in the smooth muscle of the pig and human urinary bladder was assessed on the basis of the relative potency of alpha- and beta-adrenoceptor agonists and antagonists.2 In isolated, carbachol-contracted bladder strips from the pig detrusor muscle the relaxing potency of isoprenaline was four times that of salbutamol and ritodrine and thirty times that of noradrenaline.3 Propranolol caused a parallel shift to the right of the noradrenaline dose-response curve which was not changed by phentolamine.4 Propranolol and butoxamine showed, in contrast to practolol, a dose-dependent antagonism of the response to isoprenaline. A pA(2) value of 9.2 +/- 0.2 and 6.8 +/- 0.2 (mean +/- s.e. mean) for the first two antagonists was calculated.5 In the bladder base of the pig, propranolol caused a parallel shift to the right and phentolamine a shift to the left of the dose-response curve to noradrenaline.6 In the human detrusor muscle the potency and maximum effect of isoprenaline and salbutamol were less than those in the pig detrusor muscle. The potency of isoprenaline was sixty times that of salbutamol.7 Whereas a parallel shift to the right of the dose-response curve to isoprenaline was obtained with propranolol, no antagonism was obtained with butoxamine or practolol.8 The results are interpreted as indicating the presence of beta(2)-adrenoceptors in the detrusor muscle of the pig and beta-adrenoceptors with neither beta(1)- nor beta(2)-characteristics in the detrusor muscle of man. An indication of the presence of alpha-adrenoceptors in the bladder base but not in the detrusor muscle of the pig was obtained.", "contents": "alpha And beta-adrenoceptors in the detrusor muscle and bladder base of the pig and beta-adrenoceptors in the detrusor muscle of man. 1 The presence and type of adrenoceptors in the smooth muscle of the pig and human urinary bladder was assessed on the basis of the relative potency of alpha- and beta-adrenoceptor agonists and antagonists.2 In isolated, carbachol-contracted bladder strips from the pig detrusor muscle the relaxing potency of isoprenaline was four times that of salbutamol and ritodrine and thirty times that of noradrenaline.3 Propranolol caused a parallel shift to the right of the noradrenaline dose-response curve which was not changed by phentolamine.4 Propranolol and butoxamine showed, in contrast to practolol, a dose-dependent antagonism of the response to isoprenaline. A pA(2) value of 9.2 +/- 0.2 and 6.8 +/- 0.2 (mean +/- s.e. mean) for the first two antagonists was calculated.5 In the bladder base of the pig, propranolol caused a parallel shift to the right and phentolamine a shift to the left of the dose-response curve to noradrenaline.6 In the human detrusor muscle the potency and maximum effect of isoprenaline and salbutamol were less than those in the pig detrusor muscle. The potency of isoprenaline was sixty times that of salbutamol.7 Whereas a parallel shift to the right of the dose-response curve to isoprenaline was obtained with propranolol, no antagonism was obtained with butoxamine or practolol.8 The results are interpreted as indicating the presence of beta(2)-adrenoceptors in the detrusor muscle of the pig and beta-adrenoceptors with neither beta(1)- nor beta(2)-characteristics in the detrusor muscle of man. An indication of the presence of alpha-adrenoceptors in the bladder base but not in the detrusor muscle of the pig was obtained."}
{"id": "PMID:216453", "title": "Comparison of pre-junctional alpha-adrenoceptors at the neuromuscular junction with vascular post-junctional alpha-receptors in cat skeletal muscle.", "content": "1 Activation of pre-junctional alpha-adrenoceptors at the skeletal neuromuscular junction enhances acetylcholine release whereas activation of such receptors at autonomic nerve endings inhibits transmitter output. In the present study the characteristics of pre-junctional alpha-adrenoceptors at motor nerve terminals have been compared with post-junctional (vascular) alpha-adrenoceptors in the cat hind limb.2 Reversal of partial (+)-tubocurarine blockade of contractions of the tibialis anterior muscle was used to monitor pre-junctional activity and increases in hindlimb vascular resistance to assess post-junctional actions at alpha-adrenoceptors.3 Responses to intra-arterial injections of noradrenaline, adrenaline, phenylephrine, oxymetazoline, methoxamine and clonidine were monitored. Dose-response lines for all the compounds except clonidine were parallel. The latter agent produced only weak and inconsistent effects.4 Ratios of the doses of the agents required to produce pre- and post-junctional effects indicated that oxymetazoline and adrenaline possessed some preferential activity at post-junctional sites, whereas the remaining agents were non-selective in their actions. If dose-ratios with respect to noradrenaline were compared at the two sites none of the compounds possessed a marked degree of selectivity.5 In the presence of phentolamine or tolazoline, dose-response curves to the pre- and post-junctional effects of phenylephrine were shifted to a similar extent. Thymoxamine showed preferential activity as a pre-junctional alpha-receptor antagonist.6 In comparing the results of this study with those of other authors, it is apparent that there are marked differences in the characteristics of pre-junctional alpha-receptors at the skeletal neuromuscular junction and at autonomic nerve endings. The pre- and post-junctional alpha-receptors in skeletal muscle show less divergence.", "contents": "Comparison of pre-junctional alpha-adrenoceptors at the neuromuscular junction with vascular post-junctional alpha-receptors in cat skeletal muscle. 1 Activation of pre-junctional alpha-adrenoceptors at the skeletal neuromuscular junction enhances acetylcholine release whereas activation of such receptors at autonomic nerve endings inhibits transmitter output. In the present study the characteristics of pre-junctional alpha-adrenoceptors at motor nerve terminals have been compared with post-junctional (vascular) alpha-adrenoceptors in the cat hind limb.2 Reversal of partial (+)-tubocurarine blockade of contractions of the tibialis anterior muscle was used to monitor pre-junctional activity and increases in hindlimb vascular resistance to assess post-junctional actions at alpha-adrenoceptors.3 Responses to intra-arterial injections of noradrenaline, adrenaline, phenylephrine, oxymetazoline, methoxamine and clonidine were monitored. Dose-response lines for all the compounds except clonidine were parallel. The latter agent produced only weak and inconsistent effects.4 Ratios of the doses of the agents required to produce pre- and post-junctional effects indicated that oxymetazoline and adrenaline possessed some preferential activity at post-junctional sites, whereas the remaining agents were non-selective in their actions. If dose-ratios with respect to noradrenaline were compared at the two sites none of the compounds possessed a marked degree of selectivity.5 In the presence of phentolamine or tolazoline, dose-response curves to the pre- and post-junctional effects of phenylephrine were shifted to a similar extent. Thymoxamine showed preferential activity as a pre-junctional alpha-receptor antagonist.6 In comparing the results of this study with those of other authors, it is apparent that there are marked differences in the characteristics of pre-junctional alpha-receptors at the skeletal neuromuscular junction and at autonomic nerve endings. The pre- and post-junctional alpha-receptors in skeletal muscle show less divergence."}
{"id": "PMID:216454", "title": "Depolarization of neurones in the isolated olfactory cortex of the guinea-pig by gamma-aminobutyric acid.", "content": "1 Effects of gamma-aminobutyric acid (GABA) on single neurones in slices of guinea-pig olfactory cortex maintained in vitro were recorded with single intracellular microelectrodes. The average resting potential of 52 cells was -75 mV and apparent input resistance ranged from 20 to 200 MOmega.2 Superfusions of GABA over the slice invariably depolarized the neurones and reduced their input resistance. The minimum effective concentration was 50 to 200 muM.3 The reversal potential for the depolarization produced by 0.1 mM GABA (E(g)) was -66 +/- 2 mV. At concentrations >0.1 mM the reversal potential became progressively more positive (-55 to -50 mV).4 Reduction of external chloride, with isethionate as the substitute anion, increased the amplitude of the depolarization.5 GABA reduced the amplitude of the excitatory postsynaptic potential produced by lateral olfactory tract stimulation, and occluded or reversed the subsequent depolarizing recurrent inhibitory postsynaptic potential.6 Action potentials elicited by injection of depolarizing current or by focal antidromic stimulation were slowed and reduced in amplitude by GABA.7 The effects of GABA on membrane conductance (potency = 1) were duplicated by 3-aminopropanesulphonic acid (potency = 20), beta-alanine (0.5), beta-amino-n-butyric acid (0.5), glycine (0.3) and L-2,4-diaminobutyric acid (0.2). For a given conductance change, 3-aminopropanesulphonic acid, glycine and beta-alanine produced less depolarization than did GABA.8 It is concluded that the action of GABA on the neurones is compatible with a role in mediating recurrent postsynaptic inhibition.", "contents": "Depolarization of neurones in the isolated olfactory cortex of the guinea-pig by gamma-aminobutyric acid. 1 Effects of gamma-aminobutyric acid (GABA) on single neurones in slices of guinea-pig olfactory cortex maintained in vitro were recorded with single intracellular microelectrodes. The average resting potential of 52 cells was -75 mV and apparent input resistance ranged from 20 to 200 MOmega.2 Superfusions of GABA over the slice invariably depolarized the neurones and reduced their input resistance. The minimum effective concentration was 50 to 200 muM.3 The reversal potential for the depolarization produced by 0.1 mM GABA (E(g)) was -66 +/- 2 mV. At concentrations >0.1 mM the reversal potential became progressively more positive (-55 to -50 mV).4 Reduction of external chloride, with isethionate as the substitute anion, increased the amplitude of the depolarization.5 GABA reduced the amplitude of the excitatory postsynaptic potential produced by lateral olfactory tract stimulation, and occluded or reversed the subsequent depolarizing recurrent inhibitory postsynaptic potential.6 Action potentials elicited by injection of depolarizing current or by focal antidromic stimulation were slowed and reduced in amplitude by GABA.7 The effects of GABA on membrane conductance (potency = 1) were duplicated by 3-aminopropanesulphonic acid (potency = 20), beta-alanine (0.5), beta-amino-n-butyric acid (0.5), glycine (0.3) and L-2,4-diaminobutyric acid (0.2). For a given conductance change, 3-aminopropanesulphonic acid, glycine and beta-alanine produced less depolarization than did GABA.8 It is concluded that the action of GABA on the neurones is compatible with a role in mediating recurrent postsynaptic inhibition."}
{"id": "PMID:216458", "title": "Selective blockade by scopolamine of synaptic responses in cat's caudate nucleus and its modification by lesions of the substantia nigra.", "content": "Because it is commonly believed that acetylcholine is a synaptic transmitter in the caudate nucleus and that the reduction of striatal biogenic amines in Parkinson's disease leads to acetylcholine supersensitivity in the caudate nucleus, we investigated the effects of the muscarinic blocking agent scopolamine on synaptic responses of neurons in the intact feline caudate nucleus and in the caudate nucleus depleted of dopamine by long-standing nigrostriatal lesions. In the intact caudate nucleus, micro-iontophoretic application of scopolamine selectively blocked the neuronal responses to stimulation of the caudate nucleus near the recording site without affecting the responses to stimulation of the sensorimotor cortex or the substantia nigra in the same fashion. This suggests that acetylcholine is a synaptic transmitter of caudate interneurons. Responses to thalamic stimuli were also blocked by scopolamine, suggesting that acetylcholine may be a transmitter of thalamic afferents although the course of these afferents is unclear. In the dopamine-depleted caudate nucleus scopolamine was more effective than in the intact caudate nucleus blocking the neuronal responses to stimulation of the caudate nucleus. This greater blocking effect by scopolamine suggests an increased effect of endogenous acetylcholine in this response and supports previous observations of an increased excitatory effect of iontophoretic acetylcholine in the dopamine-depleted caudate nucleus. These results suggest that the acetylcholine supersensitivity which follows nigrostriatal degeneration may be due to increased effectiveness of synaptic transmission by cholinergic interneurons in the caudate nucleus.", "contents": "Selective blockade by scopolamine of synaptic responses in cat's caudate nucleus and its modification by lesions of the substantia nigra. Because it is commonly believed that acetylcholine is a synaptic transmitter in the caudate nucleus and that the reduction of striatal biogenic amines in Parkinson's disease leads to acetylcholine supersensitivity in the caudate nucleus, we investigated the effects of the muscarinic blocking agent scopolamine on synaptic responses of neurons in the intact feline caudate nucleus and in the caudate nucleus depleted of dopamine by long-standing nigrostriatal lesions. In the intact caudate nucleus, micro-iontophoretic application of scopolamine selectively blocked the neuronal responses to stimulation of the caudate nucleus near the recording site without affecting the responses to stimulation of the sensorimotor cortex or the substantia nigra in the same fashion. This suggests that acetylcholine is a synaptic transmitter of caudate interneurons. Responses to thalamic stimuli were also blocked by scopolamine, suggesting that acetylcholine may be a transmitter of thalamic afferents although the course of these afferents is unclear. In the dopamine-depleted caudate nucleus scopolamine was more effective than in the intact caudate nucleus blocking the neuronal responses to stimulation of the caudate nucleus. This greater blocking effect by scopolamine suggests an increased effect of endogenous acetylcholine in this response and supports previous observations of an increased excitatory effect of iontophoretic acetylcholine in the dopamine-depleted caudate nucleus. These results suggest that the acetylcholine supersensitivity which follows nigrostriatal degeneration may be due to increased effectiveness of synaptic transmission by cholinergic interneurons in the caudate nucleus."}
{"id": "PMID:216459", "title": "Responses of single units in laminae 2 and 3 of cat spinal cord.", "content": "333 units were recorded in laminae 2 and 3 of lumbar cord in decerebrate cats. Recording of small-amplitude spikes was made possible by the use of platinum-surfaced tungsten microelectrodes, continuously variable filters and an analogue delay line display. Stimulation of the lateral Lissauer tract showed that a sample of the units sent axons into this tract. Using iron-plated electrodes, recording sites were marked and shown to be within laminae 2 and 3. Axons of peripheral afferent axons were excluded from the sample, as were long-range descending axons. By using one electrode placed close to a cell body in lamina 4 and a roving electrode in the dendritic region dorsal to the cell body, it was possible to show that the recorded units were not field spread of deeper cells. Of the units 94% had peripheral receptive fields, RF; 30% had small RFs less than 2 sq.cm, intermediate in size between RFs of peripheral axons and RFs of large cells in dorsal horn. These small RF cells occurred in clusters and their RFs constituted a fraction of the larger RF of nearby large cells. Of the units 56% responded to brush and touch, 19% to brush, touch and pressure, while 19% required pressure on skin to excite them. Latency of response to electrical stimulation showed that all cells were excited by myelinated afferents. While no cells were detected exclusively by C afferents, many may have been excited by both A and C afferents. Eighteen per cent of the cells showed a prolonged discharge lasting more than 5 sec after a single stimulus. Some of these long discharge cells continued firing for minutes. Another unusual class, 14% of all cells, habituated very powerfully to intermittant natural or electrical stimuli, and remained unresponsive for many seconds after responding to the first stimulus.", "contents": "Responses of single units in laminae 2 and 3 of cat spinal cord. 333 units were recorded in laminae 2 and 3 of lumbar cord in decerebrate cats. Recording of small-amplitude spikes was made possible by the use of platinum-surfaced tungsten microelectrodes, continuously variable filters and an analogue delay line display. Stimulation of the lateral Lissauer tract showed that a sample of the units sent axons into this tract. Using iron-plated electrodes, recording sites were marked and shown to be within laminae 2 and 3. Axons of peripheral afferent axons were excluded from the sample, as were long-range descending axons. By using one electrode placed close to a cell body in lamina 4 and a roving electrode in the dendritic region dorsal to the cell body, it was possible to show that the recorded units were not field spread of deeper cells. Of the units 94% had peripheral receptive fields, RF; 30% had small RFs less than 2 sq.cm, intermediate in size between RFs of peripheral axons and RFs of large cells in dorsal horn. These small RF cells occurred in clusters and their RFs constituted a fraction of the larger RF of nearby large cells. Of the units 56% responded to brush and touch, 19% to brush, touch and pressure, while 19% required pressure on skin to excite them. Latency of response to electrical stimulation showed that all cells were excited by myelinated afferents. While no cells were detected exclusively by C afferents, many may have been excited by both A and C afferents. Eighteen per cent of the cells showed a prolonged discharge lasting more than 5 sec after a single stimulus. Some of these long discharge cells continued firing for minutes. Another unusual class, 14% of all cells, habituated very powerfully to intermittant natural or electrical stimuli, and remained unresponsive for many seconds after responding to the first stimulus."}
{"id": "PMID:216460", "title": "Opiate-like excitatory effects of steroid sulfates and calcium-complexing agents given cerebroventricularly.", "content": "Intracerebroventricular administration of 10--20 microgram of steroid-O-sulfates induced hypermotility, agitation, salivation, EEG abnormalities, stereotypies, wet dog shakes and seizures. Equivalent effects resulted from 30--200 microgram morphine sulfate (H2SO4 salt), 50 microgram EGTA or 300--400 microgram of sodium sulfate or phosphate, but not chloride, nitrate or acetate. Non-steroid sulfates, steroid glucuronides and steroid phosphates were inactive. Naloxone, previously found to antagonize the excitatory effects of androsterone sulfate, failed to antagonize those of cortisol sulfate, sodium sulfate or EGTA. These findings suggest a role for extracellular calcium ions and for sulfate derived from circulating steroids in central responses to opiates.", "contents": "Opiate-like excitatory effects of steroid sulfates and calcium-complexing agents given cerebroventricularly. Intracerebroventricular administration of 10--20 microgram of steroid-O-sulfates induced hypermotility, agitation, salivation, EEG abnormalities, stereotypies, wet dog shakes and seizures. Equivalent effects resulted from 30--200 microgram morphine sulfate (H2SO4 salt), 50 microgram EGTA or 300--400 microgram of sodium sulfate or phosphate, but not chloride, nitrate or acetate. Non-steroid sulfates, steroid glucuronides and steroid phosphates were inactive. Naloxone, previously found to antagonize the excitatory effects of androsterone sulfate, failed to antagonize those of cortisol sulfate, sodium sulfate or EGTA. These findings suggest a role for extracellular calcium ions and for sulfate derived from circulating steroids in central responses to opiates."}
{"id": "PMID:216463", "title": "Analysis of the habituation-like changes in transmission in the temporodentate pathway of the rat.", "content": "Habituation-like decrements in extracellular measures of synaptic activation (population EPSP) and cell discharge (population spike) were analyzed in the dentate gyrus of the rat following repetitive low-frequency stimulation of the medial and lateral entorhinal cortex. Stimulation of either subdivision of the entorhinal projection system resulted in comparable habituation-like response decrements with similar stimulation regimens. However, habituating stimulation of one subdivision did not result in decreased responsiveness to stimulation of the other. Repetitive low-frequency stimulation or even a single pulse delivered to either subdivision did, however, result in a potentiation of granule cell discharge in response to stimulation of the other subdivision (a form of heterosynaptic potentiation). This heterosynaptic potentiation of granule cell discharge was not accompanied by any increase  in the extracellular EPSP. Comparisons of the relationship between the population EPSP and population spike before and during habituating stimulation revealed changes in cell discharge in response to the habituating stimulus which could not be accounted for by changes in synaptic activation alone. The results suggest that repetitive activation of the temporodentate pathway alters granule cell output as a result of two processes, a habituation-like decrement in synaptic activation, and a potentiation of granule cell discharge as a consequence of prior activation.", "contents": "Analysis of the habituation-like changes in transmission in the temporodentate pathway of the rat. Habituation-like decrements in extracellular measures of synaptic activation (population EPSP) and cell discharge (population spike) were analyzed in the dentate gyrus of the rat following repetitive low-frequency stimulation of the medial and lateral entorhinal cortex. Stimulation of either subdivision of the entorhinal projection system resulted in comparable habituation-like response decrements with similar stimulation regimens. However, habituating stimulation of one subdivision did not result in decreased responsiveness to stimulation of the other. Repetitive low-frequency stimulation or even a single pulse delivered to either subdivision did, however, result in a potentiation of granule cell discharge in response to stimulation of the other subdivision (a form of heterosynaptic potentiation). This heterosynaptic potentiation of granule cell discharge was not accompanied by any increase  in the extracellular EPSP. Comparisons of the relationship between the population EPSP and population spike before and during habituating stimulation revealed changes in cell discharge in response to the habituating stimulus which could not be accounted for by changes in synaptic activation alone. The results suggest that repetitive activation of the temporodentate pathway alters granule cell output as a result of two processes, a habituation-like decrement in synaptic activation, and a potentiation of granule cell discharge as a consequence of prior activation."}
{"id": "PMID:216464", "title": "The effect of hypothalamic hemi-islands on compensatory adrenal growth.", "content": "Unilateral hypothalamic disconnections were made with a Hal\u00e1sz knife in young male rats to determine the effects of these lesions on adrenal weight, and the response to unilateral adrenalectomy. Rats were unilaterally adrenalectomized or sham-adrenalectomized 5-7 days after the hypothalamic surgery. No lesion affected adrenal weight in sham-adrenalectomized rats. Compensatory adrenal growth 3 days after unilateral adrenalectomy is prevented by a unilateral hypothalamic hemi-island on the side ipsilateral, not contralateral, to the first removed adrenal (P less than 0.01). Portions of the ipsilateral hemi-island were examined to determine which interrupted the compensatory adrenal growth response. The anterior 90 degrees portion enhanced compensatory adrenal growth (P less than 0.01). The posterior 90 degrees portion only partially inhibited compensatory adrenal growth (P less than 0.05), while the posterolateral portion completely inhibited the response (P less than 0.01). Plasma ACTH and corticosterone levels at the time of sacrifice were unaffected by unilateral adrenalectomy, but were slightly elevated by the hypothalamic cuts. These studies provide further evidence that compensatory adrenal growth is mediated neurally.", "contents": "The effect of hypothalamic hemi-islands on compensatory adrenal growth. Unilateral hypothalamic disconnections were made with a Hal\u00e1sz knife in young male rats to determine the effects of these lesions on adrenal weight, and the response to unilateral adrenalectomy. Rats were unilaterally adrenalectomized or sham-adrenalectomized 5-7 days after the hypothalamic surgery. No lesion affected adrenal weight in sham-adrenalectomized rats. Compensatory adrenal growth 3 days after unilateral adrenalectomy is prevented by a unilateral hypothalamic hemi-island on the side ipsilateral, not contralateral, to the first removed adrenal (P less than 0.01). Portions of the ipsilateral hemi-island were examined to determine which interrupted the compensatory adrenal growth response. The anterior 90 degrees portion enhanced compensatory adrenal growth (P less than 0.01). The posterior 90 degrees portion only partially inhibited compensatory adrenal growth (P less than 0.05), while the posterolateral portion completely inhibited the response (P less than 0.01). Plasma ACTH and corticosterone levels at the time of sacrifice were unaffected by unilateral adrenalectomy, but were slightly elevated by the hypothalamic cuts. These studies provide further evidence that compensatory adrenal growth is mediated neurally."}
{"id": "PMID:216465", "title": "Spontaneous phagocytosis of C-type synaptic terminals by spinal alpha-motoneurons in newborn kittens. An electron microscopic study.", "content": "The cell bodies and proximal dendrites of spinal alpha-motoneurons were studied electron microscopically with the aid of serial sections during the first postnatal week in the cat. The observations suggested that some of the synaptic terminals of the so-called C-type on the cell bodies and dendrites are phagocytosed by the motoneurons during the first few days after birth. This finding is discussed in relation to the earlier demonstrated postnatal loss of synaptic terminals on the motoneurons after birth and differences demonstrated between different functional types of spinal motoneurons with respect to the number and distribution of C-type terminals in the adult cat.", "contents": "Spontaneous phagocytosis of C-type synaptic terminals by spinal alpha-motoneurons in newborn kittens. An electron microscopic study. The cell bodies and proximal dendrites of spinal alpha-motoneurons were studied electron microscopically with the aid of serial sections during the first postnatal week in the cat. The observations suggested that some of the synaptic terminals of the so-called C-type on the cell bodies and dendrites are phagocytosed by the motoneurons during the first few days after birth. This finding is discussed in relation to the earlier demonstrated postnatal loss of synaptic terminals on the motoneurons after birth and differences demonstrated between different functional types of spinal motoneurons with respect to the number and distribution of C-type terminals in the adult cat."}
{"id": "PMID:216466", "title": "Postsynaptic potentials recorded from medullary neurones following stimulation of carotid sinus nerve.", "content": "Projections of the carotid sinus nerve (CSN) onto medullary neurones were studied with intracellular recording. Three types of postsynaptic potentials (EPSP, EP-IPSP and IPSP) were recorded by stimulation of the ipsilateral CSN. Of the total of 121 neurones, positions of 54 were identified by intracellular dye. The other 67 were positioned by extrapolation. They were distributed over 5 medullary nuclei: (1) nucleus of the solitary tract (NTS); (2) paramedian reticular nucleus (NPR); (3) perihypoglossal nucleus (PXII); (4) lateral tegmental field (FTL); and (5) nucleus ambiguus. Since penetration of microelectrodes and injection of dye into the NTS neurones was difficult, neurones of the other 4 nuclei were examined. The IPSPs were dominant in small NPR neurones, while the EPSPs were dominant in large neurones of the other 3 nuclei. Both the NA and PXII neurones showed forms of a motor type neurone, while the FTL neurones showed various forms. The EPSPs with onset latency as short as 2-4 msec were frequently recorded in different nuclei. This strongly suggests that the CSN projects monosynaptically onto different nuclei in the medulla.", "contents": "Postsynaptic potentials recorded from medullary neurones following stimulation of carotid sinus nerve. Projections of the carotid sinus nerve (CSN) onto medullary neurones were studied with intracellular recording. Three types of postsynaptic potentials (EPSP, EP-IPSP and IPSP) were recorded by stimulation of the ipsilateral CSN. Of the total of 121 neurones, positions of 54 were identified by intracellular dye. The other 67 were positioned by extrapolation. They were distributed over 5 medullary nuclei: (1) nucleus of the solitary tract (NTS); (2) paramedian reticular nucleus (NPR); (3) perihypoglossal nucleus (PXII); (4) lateral tegmental field (FTL); and (5) nucleus ambiguus. Since penetration of microelectrodes and injection of dye into the NTS neurones was difficult, neurones of the other 4 nuclei were examined. The IPSPs were dominant in small NPR neurones, while the EPSPs were dominant in large neurones of the other 3 nuclei. Both the NA and PXII neurones showed forms of a motor type neurone, while the FTL neurones showed various forms. The EPSPs with onset latency as short as 2-4 msec were frequently recorded in different nuclei. This strongly suggests that the CSN projects monosynaptically onto different nuclei in the medulla."}
{"id": "PMID:216467", "title": "Two pharmacologically distinct histamine receptors mediating membrane hyperpolarization on identified neurons of Aplysia californica.", "content": "Two distinct hyperpolarizing responses are produced when histamine is iontophoretically applied onto the somal membranes of identified neurons within the cerebral ganglion of Aplysia: a biphasic response consisting of a rapid component (less than 5 sec) usually superimposed upon a slowly developing component; or a monophasic slowly developing response 5-20 sec in duration. The reversal potential values for the fast (typically -65 mV) and the slow (typically -89 mV) responses, and their shift to new values when the external potassium or chloride concentrations were altered, revealed that the fast and slow potentials are produced predominantly by conductance increases to chloride and potassium ions, respectively. The effects of histamine H1- and H2-receptor agonists and antagonists were studied to characterize the pharmacological properties of histamine receptors mediating these two ionically dissimilar hyperpolarizing responses. The slow potassium-dependent hyperpolarization could be mimicked by several histamine analogues; the most potent tested were the H1-receptor agonist, 2-methylhistamine, and the H2-receptor agonist, 4-methylhistamine. Neither of these agents mimicked the fast chloride-dependent histamine response. The slow potassium-dependent responses induced by histamine or histamine agonists were completely and reversibly blocked by the H2-receptor antagonist, cimetidine. By contrast, the slow potassium-dependent hyperpolarizations produced by iontophoretically applied acetylcholine or by dopamine to the same neurons were unaffected by cimetidine. Other H1 and H2 antagonists tested were either ineffective, or only partially blocked the slow hyperpolarizations in a non-selective manner. The fast chloride-dependent hyperpolarizations were not selectively antagonized by any of the H1 or H2 reagents tested, although they were effectively suppressed by tubocurarine and strychnine. These data indicate that two pharmacologically distinct histamine receptors mediate potassium- and chloride-dependent hyperpolarizations in Aplysia neurons. Neither of these receptors, however, could be classified as strictly H1 or H2 according to criteria presently used in non-neuronal tissues. The selectivity and reversibility of cimetidine indicate that this particular antihistaminic could be a valuable pharmacological tool for defining putative histaminergic synapses in Aplysia and perhaps other nervous systems.", "contents": "Two pharmacologically distinct histamine receptors mediating membrane hyperpolarization on identified neurons of Aplysia californica. Two distinct hyperpolarizing responses are produced when histamine is iontophoretically applied onto the somal membranes of identified neurons within the cerebral ganglion of Aplysia: a biphasic response consisting of a rapid component (less than 5 sec) usually superimposed upon a slowly developing component; or a monophasic slowly developing response 5-20 sec in duration. The reversal potential values for the fast (typically -65 mV) and the slow (typically -89 mV) responses, and their shift to new values when the external potassium or chloride concentrations were altered, revealed that the fast and slow potentials are produced predominantly by conductance increases to chloride and potassium ions, respectively. The effects of histamine H1- and H2-receptor agonists and antagonists were studied to characterize the pharmacological properties of histamine receptors mediating these two ionically dissimilar hyperpolarizing responses. The slow potassium-dependent hyperpolarization could be mimicked by several histamine analogues; the most potent tested were the H1-receptor agonist, 2-methylhistamine, and the H2-receptor agonist, 4-methylhistamine. Neither of these agents mimicked the fast chloride-dependent histamine response. The slow potassium-dependent responses induced by histamine or histamine agonists were completely and reversibly blocked by the H2-receptor antagonist, cimetidine. By contrast, the slow potassium-dependent hyperpolarizations produced by iontophoretically applied acetylcholine or by dopamine to the same neurons were unaffected by cimetidine. Other H1 and H2 antagonists tested were either ineffective, or only partially blocked the slow hyperpolarizations in a non-selective manner. The fast chloride-dependent hyperpolarizations were not selectively antagonized by any of the H1 or H2 reagents tested, although they were effectively suppressed by tubocurarine and strychnine. These data indicate that two pharmacologically distinct histamine receptors mediate potassium- and chloride-dependent hyperpolarizations in Aplysia neurons. Neither of these receptors, however, could be classified as strictly H1 or H2 according to criteria presently used in non-neuronal tissues. The selectivity and reversibility of cimetidine indicate that this particular antihistaminic could be a valuable pharmacological tool for defining putative histaminergic synapses in Aplysia and perhaps other nervous systems."}
{"id": "PMID:216468", "title": "Divalent cation dependent phosphorylation of proteins in squid giant axon.", "content": "In vitro and in situ (after intracellular infusion) incubation of axoplasm from the squid giant axon with [gamma-32P]ATP produces a phosphorylation of primarily two proteins (of mol.wt. 200,000 and greater than 400,000). The phosphorylation of these proteins is stimulated by Mg2+, inhibited by Ca2+, and unaffected by 10(-7) to 10(-5) M cyclic nucleotides. The 200 kdalton and greater than 400 kdalton phosphorylated peaks appear to be neurofilament proteins, and phosphorylation of these peaks in situ is decreased by electrical stimulation of the axon.", "contents": "Divalent cation dependent phosphorylation of proteins in squid giant axon. In vitro and in situ (after intracellular infusion) incubation of axoplasm from the squid giant axon with [gamma-32P]ATP produces a phosphorylation of primarily two proteins (of mol.wt. 200,000 and greater than 400,000). The phosphorylation of these proteins is stimulated by Mg2+, inhibited by Ca2+, and unaffected by 10(-7) to 10(-5) M cyclic nucleotides. The 200 kdalton and greater than 400 kdalton phosphorylated peaks appear to be neurofilament proteins, and phosphorylation of these peaks in situ is decreased by electrical stimulation of the axon."}
{"id": "PMID:216471", "title": "Effects of vitamin D3 metabolites on bone cell calcium transport.", "content": "The vitamin D3 metabolite, 25-hydroxycholecalciferol, at concentrations of 0.01 to 10.0 microgram/ml, decreased calcium uptake by isolated bone cells. The effect occurred within 1 min after the simultaneous addition of metabolite and 45Ca. Lactic acid and ATP production by the cells was not affected. 24(R), 25-dihydroxycholecalciferol produced a similar decrease in calcium uptake. Vitamin D3 had no effect at concentrations from 0.01 to 10.0 micrograms/ml. No effect of 1,25-dihydroxycholecalciferol on calcium uptake was observed with concentrations from 0.1 to 100 ng/ml and various preincubation periods extending to 2 h. None of the agents had any effect on calcium efflux. The effects of 25-hydroxycholecalciferol and 24(R), 25-dihydroxycholecalciferol on calcium uptake were not seen in isolated fetal rat skin cell preparations.", "contents": "Effects of vitamin D3 metabolites on bone cell calcium transport. The vitamin D3 metabolite, 25-hydroxycholecalciferol, at concentrations of 0.01 to 10.0 microgram/ml, decreased calcium uptake by isolated bone cells. The effect occurred within 1 min after the simultaneous addition of metabolite and 45Ca. Lactic acid and ATP production by the cells was not affected. 24(R), 25-dihydroxycholecalciferol produced a similar decrease in calcium uptake. Vitamin D3 had no effect at concentrations from 0.01 to 10.0 micrograms/ml. No effect of 1,25-dihydroxycholecalciferol on calcium uptake was observed with concentrations from 0.1 to 100 ng/ml and various preincubation periods extending to 2 h. None of the agents had any effect on calcium efflux. The effects of 25-hydroxycholecalciferol and 24(R), 25-dihydroxycholecalciferol on calcium uptake were not seen in isolated fetal rat skin cell preparations."}
{"id": "PMID:216472", "title": "Hydroxyl radical production by free and DNA-bound aminoquinone antibiotics and its role in DNA degradation. Electron spin resonance detection of hydroxyl radicals by spin trapping.", "content": "The reduced antitumor antibiotic mitomycin C in aqueous solution exposed to air gives a 36-line electron spin resonance spectrum of the semiquinone identified by computer simulation. Incubation of this radical with the spin trap N-tert-butyl-alpha-phenylnitrone (PBN) gives the PBN.OH nitroxide radical identified by independent generation. This nitroxide radical is also formed from similar treatment of a DNA to which mitomycin C is covalently attached. Incubation of the semiquinone from mitomycin C, mitomycin B, or streptonigrin (SN) with catalase or with superoxide dismutase inhibits the generation of OH, implying the intermediacy of H2O2 and O2 in its formation. The formation of the spin-trapped nitroxide radical is similarly inhibited by EDTA, suggesting the intermediacy of trace metal ions in the generation of hydroxyl radicals from SN. The results are consistent with the generation by the aminoquinone antibiotics in vivo of OH. already implicated in the degradation of DNA.", "contents": "Hydroxyl radical production by free and DNA-bound aminoquinone antibiotics and its role in DNA degradation. Electron spin resonance detection of hydroxyl radicals by spin trapping. The reduced antitumor antibiotic mitomycin C in aqueous solution exposed to air gives a 36-line electron spin resonance spectrum of the semiquinone identified by computer simulation. Incubation of this radical with the spin trap N-tert-butyl-alpha-phenylnitrone (PBN) gives the PBN.OH nitroxide radical identified by independent generation. This nitroxide radical is also formed from similar treatment of a DNA to which mitomycin C is covalently attached. Incubation of the semiquinone from mitomycin C, mitomycin B, or streptonigrin (SN) with catalase or with superoxide dismutase inhibits the generation of OH, implying the intermediacy of H2O2 and O2 in its formation. The formation of the spin-trapped nitroxide radical is similarly inhibited by EDTA, suggesting the intermediacy of trace metal ions in the generation of hydroxyl radicals from SN. The results are consistent with the generation by the aminoquinone antibiotics in vivo of OH. already implicated in the degradation of DNA."}
{"id": "PMID:216473", "title": "Case report: An outbreak of herpesvirus myeloencephalitis in vaccinated horses.", "content": "In the foaling season of 1977, five vaccinated horses in a Standardbred breeding stable were affected with herpesvirus myeloencephalitis. Respiratory and abortigenic forms also occurred in other individuals on the premises. Equine herpesvirus type 1 was isolated from the brain of one case of myeloencephalitis and from lungs of two aborted fetuses. Twelve of 16 horses demonstrated fourfold or greater increases in titres to equine herpesvirus type 1.", "contents": "Case report: An outbreak of herpesvirus myeloencephalitis in vaccinated horses. In the foaling season of 1977, five vaccinated horses in a Standardbred breeding stable were affected with herpesvirus myeloencephalitis. Respiratory and abortigenic forms also occurred in other individuals on the premises. Equine herpesvirus type 1 was isolated from the brain of one case of myeloencephalitis and from lungs of two aborted fetuses. Twelve of 16 horses demonstrated fourfold or greater increases in titres to equine herpesvirus type 1."}
{"id": "PMID:216474", "title": "The role of genetic factors in the etiology of Wilms' tumor: two pairs of monozygous twins with congenital abnormalities (aniridia; hemihypertrophy) and discordance for Wilms' tumor.", "content": "Wilms' tumor was diagnosed in two children each of whom has an identical twin. In one of the pairs of twins the aniridia syndrome with psychomotor retardation was present in both children, but Wilms' tumor was found in only one. In the other twins hemihypertrophy as well as Wilms' tumor were identified in one child, whereas neither of these abnormalities was present in her twin sister. These findings lend support to a hypothesis that the development of Wilms' tumor requires the occurrence of two successive mutational events, one of which may be a germinal mutation. The presence of aniridia, hemihypertrophy, or other associated congenital abnormalities may aid in distinguishing between hereditary and sporadic forms of Wilms' tumor.", "contents": "The role of genetic factors in the etiology of Wilms' tumor: two pairs of monozygous twins with congenital abnormalities (aniridia; hemihypertrophy) and discordance for Wilms' tumor. Wilms' tumor was diagnosed in two children each of whom has an identical twin. In one of the pairs of twins the aniridia syndrome with psychomotor retardation was present in both children, but Wilms' tumor was found in only one. In the other twins hemihypertrophy as well as Wilms' tumor were identified in one child, whereas neither of these abnormalities was present in her twin sister. These findings lend support to a hypothesis that the development of Wilms' tumor requires the occurrence of two successive mutational events, one of which may be a germinal mutation. The presence of aniridia, hemihypertrophy, or other associated congenital abnormalities may aid in distinguishing between hereditary and sporadic forms of Wilms' tumor."}
{"id": "PMID:216475", "title": "Atypical fibrous histiocytoma with myxoid stroma: a rare lesion arising from dura mater of the brain.", "content": "Intracranial fibrohistiocytic tumors are rare. This report is concerned with a 24-year-old white male who had an 8 month history of intermittent visual disturbance. Craniotomy revealed a large, completely intradural lesion on the floor of the left anterior cranial fossa without involvement of the leptomeninges or brain parenchyma. Gross and microscopic examination revealed that the fibrogenic portion of the tumor was composed of spindle shaped neoplastic cells arranged in storiform pattern, a hallmark of fibrohistiocytic tumor. In contrast to three previously reported cases of \"fibrous xanthomas\" involving the leptomeninges and superficial cortex of the brain, the present lesion is clearly originated from mesenchymal stem cell of the dura. The other distinct gross and microscopic feature was the presence of myxoid component which constituted about 40% of the entire lesion. The myxoid component had not been observed in previous 5 reported cases of intracranial fibrohistiocytic lesions. Since there was cellular pleomorphism with extremely rare mitosis, it was felt that the lesion be best designated as atypical fibrous histiocytoma with myxoid stroma.", "contents": "Atypical fibrous histiocytoma with myxoid stroma: a rare lesion arising from dura mater of the brain. Intracranial fibrohistiocytic tumors are rare. This report is concerned with a 24-year-old white male who had an 8 month history of intermittent visual disturbance. Craniotomy revealed a large, completely intradural lesion on the floor of the left anterior cranial fossa without involvement of the leptomeninges or brain parenchyma. Gross and microscopic examination revealed that the fibrogenic portion of the tumor was composed of spindle shaped neoplastic cells arranged in storiform pattern, a hallmark of fibrohistiocytic tumor. In contrast to three previously reported cases of \"fibrous xanthomas\" involving the leptomeninges and superficial cortex of the brain, the present lesion is clearly originated from mesenchymal stem cell of the dura. The other distinct gross and microscopic feature was the presence of myxoid component which constituted about 40% of the entire lesion. The myxoid component had not been observed in previous 5 reported cases of intracranial fibrohistiocytic lesions. Since there was cellular pleomorphism with extremely rare mitosis, it was felt that the lesion be best designated as atypical fibrous histiocytoma with myxoid stroma."}
{"id": "PMID:216476", "title": "Reactive glioma in intracranial sarcoma: a form of mixed sarcoma and glioma (\"sarcoglioma\"): report of eight cases.", "content": "The clinicopathologic features of eight new cases of combined intracranial sarcoma and glioma are described. This type of mixed cerebral tumor is histologically characterized by a peripheral distribution of the gliomatous elements in relation to a more centrally situated meningeal or intracerebral sarcoma, and by the frequent presence of gradual transitions from reactive to frankly neoplastic astrocytes. In six of the eight cases, the additional development of either infiltrating astrocytoma or frank glioblastoma in the adjacent brain was demonstrated; this was interpreted as a further expression of malignant glial reaction. It is suggested that these tumors be termed \"sarcogliomas\" to distinguish them from the type of mixed glioma and sarcoma that has recently been redesignated \"gliosarcoma.\"", "contents": "Reactive glioma in intracranial sarcoma: a form of mixed sarcoma and glioma (\"sarcoglioma\"): report of eight cases. The clinicopathologic features of eight new cases of combined intracranial sarcoma and glioma are described. This type of mixed cerebral tumor is histologically characterized by a peripheral distribution of the gliomatous elements in relation to a more centrally situated meningeal or intracerebral sarcoma, and by the frequent presence of gradual transitions from reactive to frankly neoplastic astrocytes. In six of the eight cases, the additional development of either infiltrating astrocytoma or frank glioblastoma in the adjacent brain was demonstrated; this was interpreted as a further expression of malignant glial reaction. It is suggested that these tumors be termed \"sarcogliomas\" to distinguish them from the type of mixed glioma and sarcoma that has recently been redesignated \"gliosarcoma.\""}
{"id": "PMID:216477", "title": "Metastatic carcinoma to the tongue: a report of two cases and a review of the literature.", "content": "Metastatic tumors of the oral cavity are uncommon. Most of them are located in the mandible while only a small percentage are found within the soft tissues. Two cases of metastatic bronchogenic carcinomas to the tongue are described. Review of the literature showed that cancer of the lung was the most common primary lesion that metastasized to the soft tissues of the oral cavity. The base of the tongue was the most prevalent site of metastases to soft tissue within the oral cavity.", "contents": "Metastatic carcinoma to the tongue: a report of two cases and a review of the literature. Metastatic tumors of the oral cavity are uncommon. Most of them are located in the mandible while only a small percentage are found within the soft tissues. Two cases of metastatic bronchogenic carcinomas to the tongue are described. Review of the literature showed that cancer of the lung was the most common primary lesion that metastasized to the soft tissues of the oral cavity. The base of the tongue was the most prevalent site of metastases to soft tissue within the oral cavity."}
{"id": "PMID:216478", "title": "Systemic leishmaniasis mimicking malignant histiocytosis.", "content": "A 22-year-old man with fever, hepato-splenomegaly and severe pancytopenia is described in whom the histologic features of the spleen, liver and lymph nodes were consistent with malignant histiocytosis. Characteristic Leishman-Donovan bodies were demonstrated on a bone marrow aspirate, and the diagnosis of visceral leishmaniasis was confirmed by culturing the flagellated forms of the pathogen, and by an excellent response to sodium stibogluconate. In view of the similarity in clinical and histologic appearance, visceral leishmaniasis must be considered in the differential diagnosis of malignant histiocytosis in geographic areas where leishmaniasis is still endemic.", "contents": "Systemic leishmaniasis mimicking malignant histiocytosis. A 22-year-old man with fever, hepato-splenomegaly and severe pancytopenia is described in whom the histologic features of the spleen, liver and lymph nodes were consistent with malignant histiocytosis. Characteristic Leishman-Donovan bodies were demonstrated on a bone marrow aspirate, and the diagnosis of visceral leishmaniasis was confirmed by culturing the flagellated forms of the pathogen, and by an excellent response to sodium stibogluconate. In view of the similarity in clinical and histologic appearance, visceral leishmaniasis must be considered in the differential diagnosis of malignant histiocytosis in geographic areas where leishmaniasis is still endemic."}
{"id": "PMID:216479", "title": "Multiple pulmonary lesions in a patient treated with BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) for glioblastoma multiforme.", "content": "A patient with a glioblastoma multiforme who was treated with BCNU, developed rapidly progressive pulmonary disease. The pulmonary changes were studied pathologically and included atypical alveolar cell hyperplasia, hyaline membranes, and interstitial fibrosis. These lesions contributed to the patient's demise and may be related to the administration of BCNU.", "contents": "Multiple pulmonary lesions in a patient treated with BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) for glioblastoma multiforme. A patient with a glioblastoma multiforme who was treated with BCNU, developed rapidly progressive pulmonary disease. The pulmonary changes were studied pathologically and included atypical alveolar cell hyperplasia, hyaline membranes, and interstitial fibrosis. These lesions contributed to the patient's demise and may be related to the administration of BCNU."}
{"id": "PMID:216480", "title": "Detection of humoral immune response to human brain tumors: specificity and reliability of microcytotoxicity assay.", "content": "A humoral microcytotoxicity assay has been used to study the immune response to human malignant astrocytic tumors. Two series are described. When the assay was performed under uniform, ideal conditions, the sera from 36 of 45 patients with these tumors (80%) produced significant cytotoxicity against allogeneic astrocytoma cells. Only 4 of 55 (7%) normal sera tested demonstrated cytotoxicity. The second series describes a five year study of over 400 sera with several sera assayed each week. The assay was found to vary in specificity and reliability over this five year period. The reasons for this variability are discussed and methods of standardizing the technique are proposed. Recent information concerning the mechanisms of the humoral microcytotoxicity assay offer promise of improved reliability and clinical utility.", "contents": "Detection of humoral immune response to human brain tumors: specificity and reliability of microcytotoxicity assay. A humoral microcytotoxicity assay has been used to study the immune response to human malignant astrocytic tumors. Two series are described. When the assay was performed under uniform, ideal conditions, the sera from 36 of 45 patients with these tumors (80%) produced significant cytotoxicity against allogeneic astrocytoma cells. Only 4 of 55 (7%) normal sera tested demonstrated cytotoxicity. The second series describes a five year study of over 400 sera with several sera assayed each week. The assay was found to vary in specificity and reliability over this five year period. The reasons for this variability are discussed and methods of standardizing the technique are proposed. Recent information concerning the mechanisms of the humoral microcytotoxicity assay offer promise of improved reliability and clinical utility."}
{"id": "PMID:216483", "title": "Inhibition of sodium-potassium-activated adenosine 5'-triphosphatase and ion transport by adriamycin.", "content": "The antitumor antibiotic Adriamycin is a potent inhibitor of the sodium-potassium-activated adenosine triphosphatase of native heart microsomes. Adriamycin also inhibits potassium transport (although not sodium transport) in slices of kidney cortex. The effects on both the adenosine triphosphatase and ion transport are markedly reduced by Ca2+, probably by chelation of this metal by Adriamycin. These effects could provide a basis for explaining the Adriamycin cardiotoxicity as a digitalis-type toxicity.", "contents": "Inhibition of sodium-potassium-activated adenosine 5'-triphosphatase and ion transport by adriamycin. The antitumor antibiotic Adriamycin is a potent inhibitor of the sodium-potassium-activated adenosine triphosphatase of native heart microsomes. Adriamycin also inhibits potassium transport (although not sodium transport) in slices of kidney cortex. The effects on both the adenosine triphosphatase and ion transport are markedly reduced by Ca2+, probably by chelation of this metal by Adriamycin. These effects could provide a basis for explaining the Adriamycin cardiotoxicity as a digitalis-type toxicity."}
{"id": "PMID:216485", "title": "Differences in the ability of human lymphoblastoid lines to exclude bromodeoxyuridine and in their sensitivity to methyl methanesulfonate and to incorporated [3H]thymidine.", "content": "Six Burkitt's lymphoma-derived lines were more resistant to methyl methanesulfonate than were six lymphoblastoid lines derived by in vitro transformation as measured by cloning ability in soft agar. The differences were due to cell response rather than to reactivity. Lymphoblastoid lines were also more sensitive to [3H]thymidine incorporated along with bromodeoxyuridine than were the lymphoma lines tested. All lines showed excision repair activity as measured by the benzoylated napthoylated DEAE cellulose method, although there were quantitative differences in the activity of different lines. Most lymphoblastoid lines synthesize DNA of lower density when incubated in analog-containing medium due to their ability to discriminate against bromodeoxyuridine and to select for thymidine in a mixture. All the lymphoma cell lines tested were unable to discriminate between thymidine and bromodeoxyuridine. The ability of lymphoma cells to produce large quantities of dense radioactive, doubly substituted DNA when incubated in medium with bromodeoxyuridine and thymidine is due to their inability to discriminate between nucleosides and to their resistance to incorporated [3H]thymidine.", "contents": "Differences in the ability of human lymphoblastoid lines to exclude bromodeoxyuridine and in their sensitivity to methyl methanesulfonate and to incorporated [3H]thymidine. Six Burkitt's lymphoma-derived lines were more resistant to methyl methanesulfonate than were six lymphoblastoid lines derived by in vitro transformation as measured by cloning ability in soft agar. The differences were due to cell response rather than to reactivity. Lymphoblastoid lines were also more sensitive to [3H]thymidine incorporated along with bromodeoxyuridine than were the lymphoma lines tested. All lines showed excision repair activity as measured by the benzoylated napthoylated DEAE cellulose method, although there were quantitative differences in the activity of different lines. Most lymphoblastoid lines synthesize DNA of lower density when incubated in analog-containing medium due to their ability to discriminate against bromodeoxyuridine and to select for thymidine in a mixture. All the lymphoma cell lines tested were unable to discriminate between thymidine and bromodeoxyuridine. The ability of lymphoma cells to produce large quantities of dense radioactive, doubly substituted DNA when incubated in medium with bromodeoxyuridine and thymidine is due to their inability to discriminate between nucleosides and to their resistance to incorporated [3H]thymidine."}
{"id": "PMID:216487", "title": "Imidoester inhibition of lymphocyte DNA synthesis.", "content": "Imidoesters amidinate free amino groups and produce inter- and intramolecular covalent bonds. To determine whether imidoesters influenced lymphocyte transformation, human peripheral blood or calf lymph node lymphocytes were cultured with dimethyladipimate (DMA), a bifunctional (cross-linking) imidoester, or methyl acetimidate (MAC), a monofunctional (noncross-linking) imidoester. Both DMA and MAC decreased the rate of endogenous DNA synthesis in a dose-dependent fashion. In further work, lymphocytes were treated with Phaseolus vulgaris phytohemagglutinin, concanavalin A, or periodate. DMA (1 mM) decreased DNA synthesis in P. vulgaris phytohemagglutinin-stimulated human cells by 65%, Concanavalin A-stimulated cells by 98.2%, and periodate-stimulated cells by 85%. Similar results were obtained with 1 mM MAC. Inhibition by DMA was slightly greater than was the inhibition by MAC. Decreased DNA synthesis resulted if DMA was added to P. vulgaris phytohemagglutinin-stimulated human lymphocytes at initiation of culture (72%) or after 16 hr (75%); inhibition was less when DMA was added after 24 hr (43%) and was not apparent if added after 48 hr. Therefore, both monofunctional and bifunctional imidoesters inhibit endogenous and stimulated DNA synthesis in human and calf lymphocytes.", "contents": "Imidoester inhibition of lymphocyte DNA synthesis. Imidoesters amidinate free amino groups and produce inter- and intramolecular covalent bonds. To determine whether imidoesters influenced lymphocyte transformation, human peripheral blood or calf lymph node lymphocytes were cultured with dimethyladipimate (DMA), a bifunctional (cross-linking) imidoester, or methyl acetimidate (MAC), a monofunctional (noncross-linking) imidoester. Both DMA and MAC decreased the rate of endogenous DNA synthesis in a dose-dependent fashion. In further work, lymphocytes were treated with Phaseolus vulgaris phytohemagglutinin, concanavalin A, or periodate. DMA (1 mM) decreased DNA synthesis in P. vulgaris phytohemagglutinin-stimulated human cells by 65%, Concanavalin A-stimulated cells by 98.2%, and periodate-stimulated cells by 85%. Similar results were obtained with 1 mM MAC. Inhibition by DMA was slightly greater than was the inhibition by MAC. Decreased DNA synthesis resulted if DMA was added to P. vulgaris phytohemagglutinin-stimulated human lymphocytes at initiation of culture (72%) or after 16 hr (75%); inhibition was less when DMA was added after 24 hr (43%) and was not apparent if added after 48 hr. Therefore, both monofunctional and bifunctional imidoesters inhibit endogenous and stimulated DNA synthesis in human and calf lymphocytes."}
{"id": "PMID:216488", "title": "Inhibition of human lymphocyte mitogen and antigen response by a 15,000-dalton protein from feline leukemia virus.", "content": "Peripheral blood lymphocyte response of normal human subjects to mitogens and antigens was suppressed by a 15,000-dalton protein (p15) from a C-type feline leukemia virus. Four of six subjects were suppressed 70 to 96% when responding to concanavalin A or phytohemagglutinin in the presence of 5.0 microgram of p15. The three subjects who responded to streptokinase-streptodornase and Candida were suppressed 68 to 91% when cultured with 5.0 microgram of p15. The subviral protein did not appear to be cytotoxic at doses reported. Lymphocyte membrane studies with fluorescein isothiocyanate-concanavalin A revealed a reduction in concanavalin A-induced cap formation of 51 to 91% in the presence of the same dose of p15. These results demonstrate that in vitro immunological dysfunction in human lymphocytes can be induced by a C-type virion protein.", "contents": "Inhibition of human lymphocyte mitogen and antigen response by a 15,000-dalton protein from feline leukemia virus. Peripheral blood lymphocyte response of normal human subjects to mitogens and antigens was suppressed by a 15,000-dalton protein (p15) from a C-type feline leukemia virus. Four of six subjects were suppressed 70 to 96% when responding to concanavalin A or phytohemagglutinin in the presence of 5.0 microgram of p15. The three subjects who responded to streptokinase-streptodornase and Candida were suppressed 68 to 91% when cultured with 5.0 microgram of p15. The subviral protein did not appear to be cytotoxic at doses reported. Lymphocyte membrane studies with fluorescein isothiocyanate-concanavalin A revealed a reduction in concanavalin A-induced cap formation of 51 to 91% in the presence of the same dose of p15. These results demonstrate that in vitro immunological dysfunction in human lymphocytes can be induced by a C-type virion protein."}
{"id": "PMID:216489", "title": "Transplantable ductal adenocarcinoma of the Syrian hamster pancreas.", "content": "A well-differentiated ductal adenocarcinoma of the Syrian golden hamster induced by N-nitrosobis(2-oxopropyl)amine was transplantable to both nude mice and inbred Syrian hamsters. The tumor grew rapidly in the nude mouse (12-fold increase in size at 45 days) in contrast to its growth in hamster (3-fold increase in size at 45 days). A curious finding associated with the slow-growing tumor in the hamster was an intense infiltration of the neoplasm by polymorphonuclear leukocytes unattended by either necrosis or infection. The neoplasm produced mucin and rapidly and specifically bound 125I-labeled secretin, although the degree of nonspecific binding (40.5%) was higher than that of control hamster pancreas (23%). Unstimulated adenyl cyclase activity (pmol cyclic adenosine 3':5'-monophosphate per mg protein) of the neoplasm was significantly higher [3.76 +/- 0.55 (S.E.)] than that of unstimulated normal hamster pancreas (1.03 +/- 0.44). Secretin did not significantly change the level of cyclic adenosine 3':5'-monophosphate (3.3 +/- 0.56) from the unstimulated level in the neoplasm, in contrast to its effect on normal pancreas where the level was increased 3-fold (3.1 +/- 0.75).", "contents": "Transplantable ductal adenocarcinoma of the Syrian hamster pancreas. A well-differentiated ductal adenocarcinoma of the Syrian golden hamster induced by N-nitrosobis(2-oxopropyl)amine was transplantable to both nude mice and inbred Syrian hamsters. The tumor grew rapidly in the nude mouse (12-fold increase in size at 45 days) in contrast to its growth in hamster (3-fold increase in size at 45 days). A curious finding associated with the slow-growing tumor in the hamster was an intense infiltration of the neoplasm by polymorphonuclear leukocytes unattended by either necrosis or infection. The neoplasm produced mucin and rapidly and specifically bound 125I-labeled secretin, although the degree of nonspecific binding (40.5%) was higher than that of control hamster pancreas (23%). Unstimulated adenyl cyclase activity (pmol cyclic adenosine 3':5'-monophosphate per mg protein) of the neoplasm was significantly higher [3.76 +/- 0.55 (S.E.)] than that of unstimulated normal hamster pancreas (1.03 +/- 0.44). Secretin did not significantly change the level of cyclic adenosine 3':5'-monophosphate (3.3 +/- 0.56) from the unstimulated level in the neoplasm, in contrast to its effect on normal pancreas where the level was increased 3-fold (3.1 +/- 0.75)."}
{"id": "PMID:216490", "title": "Cross-reactivity between Bacillus Calmette-Gu\u00e9rin and Rous Virus-induced sarcoma detected in rats by tube leukocyte adherence inhibition assay.", "content": "Specific immunity to Rous virus-induced sarcoma (RSL) was investigated by the tube leukocyte adherence inhibition (LAI) assay in rats immunized with Bacillus Calmette-Gu\u00e9rin (BCG). Peritoneal cells from Lewis rats immunized s.c. with BCG gave positive reactions in the tube LAI assay with the antigen prepared from RSL in Lewis rats. Lymph node cells from Lewis rats immunized with BCG had no cytotoxic effect on RSL cells in vitro, whereas peritoneal cells from the same rats were strongly cytotoxic for RSL cells. Growth of RSL tumors in vivo was not inhibited in BCG-treated rats as compared to that in untreated rats. The results show that LAI reactivity correlates with cytotoxicity of peritoneal cells and does not correlate with the cytotoxicity of lymph node cells and that positive LAI reactions with tumor antigen need not be reflected in the suppression of growth of the tumor in vivo.", "contents": "Cross-reactivity between Bacillus Calmette-Gu\u00e9rin and Rous Virus-induced sarcoma detected in rats by tube leukocyte adherence inhibition assay. Specific immunity to Rous virus-induced sarcoma (RSL) was investigated by the tube leukocyte adherence inhibition (LAI) assay in rats immunized with Bacillus Calmette-Gu\u00e9rin (BCG). Peritoneal cells from Lewis rats immunized s.c. with BCG gave positive reactions in the tube LAI assay with the antigen prepared from RSL in Lewis rats. Lymph node cells from Lewis rats immunized with BCG had no cytotoxic effect on RSL cells in vitro, whereas peritoneal cells from the same rats were strongly cytotoxic for RSL cells. Growth of RSL tumors in vivo was not inhibited in BCG-treated rats as compared to that in untreated rats. The results show that LAI reactivity correlates with cytotoxicity of peritoneal cells and does not correlate with the cytotoxicity of lymph node cells and that positive LAI reactions with tumor antigen need not be reflected in the suppression of growth of the tumor in vivo."}
{"id": "PMID:216492", "title": "Control of regional circulations by the sino-aortic reflexes during desynchronised sleep in the cat.", "content": "In the intact cat desynchronised sleep induces arterial hypotension and mesenteric vasodilatation, whereas in limb muscles vasoconstriction occurs because of the concurrent action of a spinal vasoconstriction reflex. After sino-aortic denervation arterial hypotension is exaggerated and mesenteric vasodilatation is greater, while the muscular bed of the limbs also becomes vasodilated rather than constricted. It is concluded that during desynchronised sleep the sino-aortic afferents act to check a central influence inhibiting vasoconstrictor tone both in the viscera and muscles: thus an excessive fall in blood pressure is prevented by avoiding a too large visceral vasodilatation and by unmasking the vasoconstrictor action of the spinal reflex in the limbs.", "contents": "Control of regional circulations by the sino-aortic reflexes during desynchronised sleep in the cat. In the intact cat desynchronised sleep induces arterial hypotension and mesenteric vasodilatation, whereas in limb muscles vasoconstriction occurs because of the concurrent action of a spinal vasoconstriction reflex. After sino-aortic denervation arterial hypotension is exaggerated and mesenteric vasodilatation is greater, while the muscular bed of the limbs also becomes vasodilated rather than constricted. It is concluded that during desynchronised sleep the sino-aortic afferents act to check a central influence inhibiting vasoconstrictor tone both in the viscera and muscles: thus an excessive fall in blood pressure is prevented by avoiding a too large visceral vasodilatation and by unmasking the vasoconstrictor action of the spinal reflex in the limbs."}
{"id": "PMID:216495", "title": "The effect of cyclic AMP on the growth and morphology of a normal human fibroblast parent strain and its transformed progeny line.", "content": "A normal human diploid fibroblast cell strain, Lederle 130 (Led 130), and its virus-transformed progeny line, transformed Led 130, were subjected to 0.75 and 1.5 mM concentrations of adenosine-5'-monophosphate (AMP), cyclic AMP (cAMP) and dibutyryl cyclic AMP (Bt2cAMP). While cAMP was markedly inhibitory to neoplastic cells at 1.5 mM, Bt2-cAMP was even more effective at this concentration, producing 85% inhibition by 4 days and 91% inhibition by 6 days. Bt2-cAMP was the only nucleotide to reverse morphological transformation effects in the neoplastic fibroblasts. Normal fibroblasts were inhibited in growth rate to a comparable extent by all nucleotides, and were not altered morphologically.", "contents": "The effect of cyclic AMP on the growth and morphology of a normal human fibroblast parent strain and its transformed progeny line. A normal human diploid fibroblast cell strain, Lederle 130 (Led 130), and its virus-transformed progeny line, transformed Led 130, were subjected to 0.75 and 1.5 mM concentrations of adenosine-5'-monophosphate (AMP), cyclic AMP (cAMP) and dibutyryl cyclic AMP (Bt2cAMP). While cAMP was markedly inhibitory to neoplastic cells at 1.5 mM, Bt2-cAMP was even more effective at this concentration, producing 85% inhibition by 4 days and 91% inhibition by 6 days. Bt2-cAMP was the only nucleotide to reverse morphological transformation effects in the neoplastic fibroblasts. Normal fibroblasts were inhibited in growth rate to a comparable extent by all nucleotides, and were not altered morphologically."}
{"id": "PMID:216496", "title": "[Toxicity of silica-gel polymers].", "content": "Mice of the ICR strain were tested for the effect of intraperitoneally applied polymers of silicagel. Silicagel applied in the form of spherical-shaped particles caused local irritation and resorptive reaction with granulocytes. There was also renal damage of the type of necronephrosis and signs of necronephrosis.", "contents": "[Toxicity of silica-gel polymers]. Mice of the ICR strain were tested for the effect of intraperitoneally applied polymers of silicagel. Silicagel applied in the form of spherical-shaped particles caused local irritation and resorptive reaction with granulocytes. There was also renal damage of the type of necronephrosis and signs of necronephrosis."}
{"id": "PMID:216497", "title": "[Changes following splenoportography or lymphography, respectively].", "content": "Lipidol deposits remaining in lymph nodes following lymphography evoke a tissue reaction of various degree. Most probably, the material injected during splenoportography may lead to storage phenomena in the reticuloendothelium of the liver.", "contents": "[Changes following splenoportography or lymphography, respectively]. Lipidol deposits remaining in lymph nodes following lymphography evoke a tissue reaction of various degree. Most probably, the material injected during splenoportography may lead to storage phenomena in the reticuloendothelium of the liver."}
{"id": "PMID:216501", "title": "Isolation of viruses from sewage, with special regard to poliovirus: an evaluation of the sensitivity of three tissue culture methods.", "content": "This report concerns experiments to isolate different viruses from sewage. Using a special cell-line from Utrecht, derived from human amniotic cells, it was possible to isolate poliovirus selectively when antisera against six types of coxsackievirus B were added to the tissue culture. The method was tested in connexion with the epidemiological investigation of a case of poliomyelitis in Sweden in 1977. It rapidly demonstrated that the virus implicated was present in all neighbouring sewage plants, indicating a wide distribution of the virus in the area.", "contents": "Isolation of viruses from sewage, with special regard to poliovirus: an evaluation of the sensitivity of three tissue culture methods. This report concerns experiments to isolate different viruses from sewage. Using a special cell-line from Utrecht, derived from human amniotic cells, it was possible to isolate poliovirus selectively when antisera against six types of coxsackievirus B were added to the tissue culture. The method was tested in connexion with the epidemiological investigation of a case of poliomyelitis in Sweden in 1977. It rapidly demonstrated that the virus implicated was present in all neighbouring sewage plants, indicating a wide distribution of the virus in the area."}
{"id": "PMID:216500", "title": "[Muco epidermoid tumor of the bronchus in a 8 year old girl (author's transl)].", "content": "A 8 year-old girl was referred with a mucoepidermoid tumor of the bronchus. Surgery was tried before a mediastin left likeness; diagnosis resided in histology of the surgical piece. Reading of medical literature, very slight for children, corroborate difficulties of histologic classification of these tumors, and especially their doubtful forecast.", "contents": "[Muco epidermoid tumor of the bronchus in a 8 year old girl (author's transl)]. A 8 year-old girl was referred with a mucoepidermoid tumor of the bronchus. Surgery was tried before a mediastin left likeness; diagnosis resided in histology of the surgical piece. Reading of medical literature, very slight for children, corroborate difficulties of histologic classification of these tumors, and especially their doubtful forecast."}
{"id": "PMID:216506", "title": "Serum cholesterol and squalene in hepatocellular carcinoma.", "content": "In 15 patients with hepatocellular carcinoma, the serum squalene level is raised significantly in parallel with the serum cholesterol level, though significantly decreased in patients with cholestatic hepatobiliary disease. Serum levels of cholesterol and/or squalene, therefore, could be regarded as a laboratory index reflecting a peculiar sterol metabolism in hepatocellular carcinoma.", "contents": "Serum cholesterol and squalene in hepatocellular carcinoma. In 15 patients with hepatocellular carcinoma, the serum squalene level is raised significantly in parallel with the serum cholesterol level, though significantly decreased in patients with cholestatic hepatobiliary disease. Serum levels of cholesterol and/or squalene, therefore, could be regarded as a laboratory index reflecting a peculiar sterol metabolism in hepatocellular carcinoma."}
{"id": "PMID:216507", "title": "Cyclic alterations of blink reflexes: an EEG and EMG study during wakefulness and sleep.", "content": "Studies of the blink reflex were undertaken in twelve normal subjects during wakefulness and different sleep stages. The early R1 and the late R2 components of the reflex were analyzed. R1 was present in only one subject during stage I sleep and subsequently disappeared in stage II to IV. In all subjects, R2 was gradually diminished and totally disappeared during stage IV. During the REM stage, R1 was seen in only four-out-of-twelve subjects but all R2 returned. Alterations of R1 and R2 of the blink reflex during different sleep stages suggest that the underlying mechanism includes both supranuclear and infranuclear activities. Our finding strengthens further the notion of dual hyponogenic mechanisms for sleep.", "contents": "Cyclic alterations of blink reflexes: an EEG and EMG study during wakefulness and sleep. Studies of the blink reflex were undertaken in twelve normal subjects during wakefulness and different sleep stages. The early R1 and the late R2 components of the reflex were analyzed. R1 was present in only one subject during stage I sleep and subsequently disappeared in stage II to IV. In all subjects, R2 was gradually diminished and totally disappeared during stage IV. During the REM stage, R1 was seen in only four-out-of-twelve subjects but all R2 returned. Alterations of R1 and R2 of the blink reflex during different sleep stages suggest that the underlying mechanism includes both supranuclear and infranuclear activities. Our finding strengthens further the notion of dual hyponogenic mechanisms for sleep."}
{"id": "PMID:216508", "title": "Stimulation of capillary tube polymorph migration: an indirect glucocorticoid effect on microtubular function.", "content": "Polymorph migration stimulator (PMS) is a peptide factor produced by an in vitro reaction between glucocorticoids and human mononuclear phagocytes. This study was undertaken to determine the significance of the stimulatory effect of PMS on the capillary tube migration of human polymorphs. Colchicine, vinblastine and Nocodazole, all of which inhibit microtubular assembly, are shown to stimulate migration. Conversely, deuterium oxide which stabilizes microtubules inhibits migration. Increased intracellular cyclic AMP is associated with microtubular inhibition and isoprenaline, theophylline and dibutyryl cyclic AMP are also found to stimulate capillary tube migration. These results suggest that PMS acts by inhibiting the assembly of polymorph microtubules, an effect which may be mediated by cyclic AMP in the same manner as other peptide hormones.", "contents": "Stimulation of capillary tube polymorph migration: an indirect glucocorticoid effect on microtubular function. Polymorph migration stimulator (PMS) is a peptide factor produced by an in vitro reaction between glucocorticoids and human mononuclear phagocytes. This study was undertaken to determine the significance of the stimulatory effect of PMS on the capillary tube migration of human polymorphs. Colchicine, vinblastine and Nocodazole, all of which inhibit microtubular assembly, are shown to stimulate migration. Conversely, deuterium oxide which stabilizes microtubules inhibits migration. Increased intracellular cyclic AMP is associated with microtubular inhibition and isoprenaline, theophylline and dibutyryl cyclic AMP are also found to stimulate capillary tube migration. These results suggest that PMS acts by inhibiting the assembly of polymorph microtubules, an effect which may be mediated by cyclic AMP in the same manner as other peptide hormones."}
{"id": "PMID:216509", "title": "Plasma levels of complement components and complement haemolytic activity in protein-energy malnutrition.", "content": "The plasma levels of complement haemolytic activity (CH50) of some complement components and of C3d, a C3 breakdown product, were measured in fifty-nine African children with various types of protein-energy malnutrition (PEM) including kwashiorkor, before and during recovery. A significant decrease of CH50, C3, C9 and factor B was observed in PEM without a concomitant decrease of C4 and C5. Increased plasma levels of C3d were also found in PEM patients. Two mechanisms seem to be involved in the impairment of the complement system in PEM: (1) a decreased synthesis of at least C3 and C9 as suggested by a significant correlation between C3 or C9, levels and those of albumin and cholinesterase; (2) an increased catabolism of C3 possibly due to an activation of the alternative complement pathway, as suggested by the increased level of C3d and the decreased level of factor B which are significantly correlated with C3 levels but not with albumin levels. These data support the possible role of a relative complement deficiency upon the decreased resistance to infections observed in malnourished children.", "contents": "Plasma levels of complement components and complement haemolytic activity in protein-energy malnutrition. The plasma levels of complement haemolytic activity (CH50) of some complement components and of C3d, a C3 breakdown product, were measured in fifty-nine African children with various types of protein-energy malnutrition (PEM) including kwashiorkor, before and during recovery. A significant decrease of CH50, C3, C9 and factor B was observed in PEM without a concomitant decrease of C4 and C5. Increased plasma levels of C3d were also found in PEM patients. Two mechanisms seem to be involved in the impairment of the complement system in PEM: (1) a decreased synthesis of at least C3 and C9 as suggested by a significant correlation between C3 or C9, levels and those of albumin and cholinesterase; (2) an increased catabolism of C3 possibly due to an activation of the alternative complement pathway, as suggested by the increased level of C3d and the decreased level of factor B which are significantly correlated with C3 levels but not with albumin levels. These data support the possible role of a relative complement deficiency upon the decreased resistance to infections observed in malnourished children."}
{"id": "PMID:216513", "title": "Adipose tissue cellularity in patients with amyotrophic lateral sclerosis.", "content": "The subcutaneous mean fat-cell volumes as measured in 20 patients suffering from amyotrophic lateral sclerosis (ALS) were definitely larger than those measured in a control group. In contrast with the control subjects, the mean fat-cell volume in patients with ALS appeared to be independent of body weight. The noted disturbances in carbohydrate-insulin metabolism in patients with ALS and the increase in serum triglycerides as observed in some patients may be related to the enlarged fat cells. The possibility that the enlargement of the fat-cells may, at least partially, have a neurogenic basis cannot be ignored. The hypothesis is put forward that in patients with ALS there is not only a lesion of the anterior horn, but also an involvement of sympathic structures responsible for the innervation of adipose tissue vessels. This involvement may lead to an inhibition of the lipolysis, and consequently to an enlargemnt of the fat cell. Interaction between the interference with metabolic and neurogenic factors may be at play.", "contents": "Adipose tissue cellularity in patients with amyotrophic lateral sclerosis. The subcutaneous mean fat-cell volumes as measured in 20 patients suffering from amyotrophic lateral sclerosis (ALS) were definitely larger than those measured in a control group. In contrast with the control subjects, the mean fat-cell volume in patients with ALS appeared to be independent of body weight. The noted disturbances in carbohydrate-insulin metabolism in patients with ALS and the increase in serum triglycerides as observed in some patients may be related to the enlarged fat cells. The possibility that the enlargement of the fat-cells may, at least partially, have a neurogenic basis cannot be ignored. The hypothesis is put forward that in patients with ALS there is not only a lesion of the anterior horn, but also an involvement of sympathic structures responsible for the innervation of adipose tissue vessels. This involvement may lead to an inhibition of the lipolysis, and consequently to an enlargemnt of the fat cell. Interaction between the interference with metabolic and neurogenic factors may be at play."}
{"id": "PMID:216514", "title": "Programmed texts: success or failure? An analysis of medical students' opinions.", "content": "It is shown that German medical textbooks have sold about nine times better than programmed texts, even if they were written by the same author and on the same subject. To explore some of the reasons why programmed texts are being used so little in comparison with conventional textbooks, 4th and 5th year medical students of the University of Berne were asked to work through a short programmed text in clinical neurology and to answer questions related to several aspects of using programmed texts and other materials. The analysis of the 212 questionnaires returned (58%) indicates that almost all students considered such a learning experience as highly useful and stimulating, but only about 25 per cent had no reservations. It is concluded that programmed medical texts may be used so little because they require students to learn in a highly standardized way, and because students need additional learning resources which provide them with  conceptual framework of and sufficient information about a given area.", "contents": "Programmed texts: success or failure? An analysis of medical students' opinions. It is shown that German medical textbooks have sold about nine times better than programmed texts, even if they were written by the same author and on the same subject. To explore some of the reasons why programmed texts are being used so little in comparison with conventional textbooks, 4th and 5th year medical students of the University of Berne were asked to work through a short programmed text in clinical neurology and to answer questions related to several aspects of using programmed texts and other materials. The analysis of the 212 questionnaires returned (58%) indicates that almost all students considered such a learning experience as highly useful and stimulating, but only about 25 per cent had no reservations. It is concluded that programmed medical texts may be used so little because they require students to learn in a highly standardized way, and because students need additional learning resources which provide them with  conceptual framework of and sufficient information about a given area."}
{"id": "PMID:216510", "title": "Reduced adenosine 3',5'-cyclic monophosphate levels in patients with reversible obstructive airways disease.", "content": "1. Patients were grouped into categories of 'no airways disease', 'obstructive airways disease without response to bronchodilator' and 'obstructive airways disease with bronchodilator responsiveness'. 2. Cyclic nucleotides were assayed in specimens of lung tissue that were excised during surgery. 3. Reduced levels of adenosine 3',5'-cyclic monophosphate (cyclic AMP) were found in pulmonary tissue obtained from patients with reversible obstructive airways disease, lending support to the beta-adrenergic theory of asthma.", "contents": "Reduced adenosine 3',5'-cyclic monophosphate levels in patients with reversible obstructive airways disease. 1. Patients were grouped into categories of 'no airways disease', 'obstructive airways disease without response to bronchodilator' and 'obstructive airways disease with bronchodilator responsiveness'. 2. Cyclic nucleotides were assayed in specimens of lung tissue that were excised during surgery. 3. Reduced levels of adenosine 3',5'-cyclic monophosphate (cyclic AMP) were found in pulmonary tissue obtained from patients with reversible obstructive airways disease, lending support to the beta-adrenergic theory of asthma."}
{"id": "PMID:216516", "title": "Computerized tomography in patients with multiple sclerosis.", "content": "In 13 of 23 patients with multiple sclerosis, studied with computerized tomography (C.T.) the lateral ventricles were found to be enlarged. In 10 cases sharply demarcated areas of low density were seen in the periventricular region, presumably representing 'plaques'. Cerebral atrophy was more frequent in those patients with a longer duration of the disease, with more exacerbations and with a greater degree of disability. Some areas of low density on C.T. scans correlated with clinical symptoms.", "contents": "Computerized tomography in patients with multiple sclerosis. In 13 of 23 patients with multiple sclerosis, studied with computerized tomography (C.T.) the lateral ventricles were found to be enlarged. In 10 cases sharply demarcated areas of low density were seen in the periventricular region, presumably representing 'plaques'. Cerebral atrophy was more frequent in those patients with a longer duration of the disease, with more exacerbations and with a greater degree of disability. Some areas of low density on C.T. scans correlated with clinical symptoms."}
{"id": "PMID:216511", "title": "Studies on the mechanism of the positive inotropic action evoked by epinine on the rabbit isolated papillary muscle at different rates of beating.", "content": "1. Effects of epinine on cyclic AMP and contractility were investigated in rabbit papillary muscles driven at a rate of 0.5 or 2.0 Hz. 2. When the frequency of stimulation was increased from 0.5 to 2.0 Hz, the log dose-response curve for the positive inotropic effect of epinine was displaced to the left, whereas the maximum of the developed tension was not changed. 3. At both frequencies phentolamine (1 mumol/l) shifted the lower part of the log dose-response curve for epinine to the right, whereas pindolol (30 nmol/l) affected mainly the upper part. In the presence of both alpha- and beta-adrenoceptor antagonists, the whole curve was shifted to the right in a parallel manner. However, cocaine (30 mumol/l) did not significantly influence the log dose-response curve of epinine. 4. At 0.5 Hz a submaximal effective concentration of epinine (100 mumol/l) led to an approximately 100% increase of the cyclic AMP level after 60s; the same increase of the cyclic AMP level was induced at 2.0 Hz by one-third the concentration of epinine (30 mumol/l). 5. Phentolamine (1 mumol/l) did not affect the increase of the cyclic AMP level evoked by epinine, whereas pindolol (30 nmol/l) completely depressed it. 6. The present results indicate that epinine produces its positive inotropic effect through direct stimulation of myocardial alpha-adrenoceptors as well as beta-adrenoceptors, depending upon the concentration: in lower concentrations it acts mainly on alpha-adrenoceptors, whereas in higher concentrations it acts predominantly on beta-adrenoceptors. The positive inotropic effect through beta-adrenoceptor stimulation is mediated by cyclic AMP, while that through alpha-adrenoceptors is not.", "contents": "Studies on the mechanism of the positive inotropic action evoked by epinine on the rabbit isolated papillary muscle at different rates of beating. 1. Effects of epinine on cyclic AMP and contractility were investigated in rabbit papillary muscles driven at a rate of 0.5 or 2.0 Hz. 2. When the frequency of stimulation was increased from 0.5 to 2.0 Hz, the log dose-response curve for the positive inotropic effect of epinine was displaced to the left, whereas the maximum of the developed tension was not changed. 3. At both frequencies phentolamine (1 mumol/l) shifted the lower part of the log dose-response curve for epinine to the right, whereas pindolol (30 nmol/l) affected mainly the upper part. In the presence of both alpha- and beta-adrenoceptor antagonists, the whole curve was shifted to the right in a parallel manner. However, cocaine (30 mumol/l) did not significantly influence the log dose-response curve of epinine. 4. At 0.5 Hz a submaximal effective concentration of epinine (100 mumol/l) led to an approximately 100% increase of the cyclic AMP level after 60s; the same increase of the cyclic AMP level was induced at 2.0 Hz by one-third the concentration of epinine (30 mumol/l). 5. Phentolamine (1 mumol/l) did not affect the increase of the cyclic AMP level evoked by epinine, whereas pindolol (30 nmol/l) completely depressed it. 6. The present results indicate that epinine produces its positive inotropic effect through direct stimulation of myocardial alpha-adrenoceptors as well as beta-adrenoceptors, depending upon the concentration: in lower concentrations it acts mainly on alpha-adrenoceptors, whereas in higher concentrations it acts predominantly on beta-adrenoceptors. The positive inotropic effect through beta-adrenoceptor stimulation is mediated by cyclic AMP, while that through alpha-adrenoceptors is not."}
{"id": "PMID:216517", "title": "Prochlorperazine in childhood: side-effects.", "content": "The side-effects of prochlorperazine (CompazineR StemetilR) were traced in thirty-six children up to the age of sixteen years and compared with those collected from literature. These side-effects appeared to be predominantly neurological and were independent of the dosage. Impaired consciousness, dyskinesia, pyramidal signs and hypertonus were the main neurological manifestations. Dyskinesia was the most frequent sign. These side-effects disappear spontaneously after discontinuation of the drug. Instant cure can be acquired by intra-muscular administration of orphenadrine (DisipalR).", "contents": "Prochlorperazine in childhood: side-effects. The side-effects of prochlorperazine (CompazineR StemetilR) were traced in thirty-six children up to the age of sixteen years and compared with those collected from literature. These side-effects appeared to be predominantly neurological and were independent of the dosage. Impaired consciousness, dyskinesia, pyramidal signs and hypertonus were the main neurological manifestations. Dyskinesia was the most frequent sign. These side-effects disappear spontaneously after discontinuation of the drug. Instant cure can be acquired by intra-muscular administration of orphenadrine (DisipalR)."}
{"id": "PMID:216518", "title": "Oculopharyngodistal myopathy with early onset and neurogenic features.", "content": "Some clinical variants of oculopharyngeal dystrophy are known; a rare form is described in this article: the early-adult form of oculopharyngodistal myopathy. The diagnosis was made in 2 patients ((brother and sister) on the grounds of extensive clinical, biochemical and morphological (microscopical, histochemical and submicroscopical) investigations. Although oculopharyngeal dystrophy is generally considered to be a purely myogenic condition, in one of our patients some neurogenic indications were found (EMG and biopsy). The general picture, however, was that of a myopathy with the characteristic morphological signs of oculopharyngeal dystrophy in the skeletal musclebiopsy.", "contents": "Oculopharyngodistal myopathy with early onset and neurogenic features. Some clinical variants of oculopharyngeal dystrophy are known; a rare form is described in this article: the early-adult form of oculopharyngodistal myopathy. The diagnosis was made in 2 patients ((brother and sister) on the grounds of extensive clinical, biochemical and morphological (microscopical, histochemical and submicroscopical) investigations. Although oculopharyngeal dystrophy is generally considered to be a purely myogenic condition, in one of our patients some neurogenic indications were found (EMG and biopsy). The general picture, however, was that of a myopathy with the characteristic morphological signs of oculopharyngeal dystrophy in the skeletal musclebiopsy."}
{"id": "PMID:216521", "title": "Glomus jugulare tumours in South Wales--a twenty-year review.", "content": "Fourteen patients with glomus jugulare tumours presenting over the last 20 years in South Wales are reviewed. All were treated with radiotherapy and only two died, both of whom had radiological evidence of extensive intrapetrosal spread. All the remainder had good relief of symptoms and are at present free from evidence of progressing tumour.", "contents": "Glomus jugulare tumours in South Wales--a twenty-year review. Fourteen patients with glomus jugulare tumours presenting over the last 20 years in South Wales are reviewed. All were treated with radiotherapy and only two died, both of whom had radiological evidence of extensive intrapetrosal spread. All the remainder had good relief of symptoms and are at present free from evidence of progressing tumour."}
{"id": "PMID:216522", "title": "The absence of 24,25-dihydroxycholecalciferol in anephric patients.", "content": "1. In subjects with normal renal function there was a strong positive correlation between serum concentrations of 25-hydroxycholecalciferol and 24,25-dihydroxycholecalciferol, as measured by competitive protein-binding assay. 2. The 24,25-dihydroxycholecalciferol concentration was about 7% of the prevailing 25-hydroxycholecalciferol concentration. 3. In contrast, sera from anephric patients contained very low or undetectable amounts of 24,25-dihydroxycholecalciferol even after the serum 25-hydroxycholecalciferol concentrations in these patients had been elevated by oral administration of 25-hydroxycholecalciferol. 4. In a further group of anephric patients, all having normal serum 25-hydroxycholecalciferol concentrations, no radioactively labelled 24,25-dihydroxycholecalciferol was formed from an injected pulse dose of [3H,14C]cholecalciferol. 5. These results indicate that in man the kidney is the major site of 24-hydroxylation of 25-hydroxycholecalciferol.", "contents": "The absence of 24,25-dihydroxycholecalciferol in anephric patients. 1. In subjects with normal renal function there was a strong positive correlation between serum concentrations of 25-hydroxycholecalciferol and 24,25-dihydroxycholecalciferol, as measured by competitive protein-binding assay. 2. The 24,25-dihydroxycholecalciferol concentration was about 7% of the prevailing 25-hydroxycholecalciferol concentration. 3. In contrast, sera from anephric patients contained very low or undetectable amounts of 24,25-dihydroxycholecalciferol even after the serum 25-hydroxycholecalciferol concentrations in these patients had been elevated by oral administration of 25-hydroxycholecalciferol. 4. In a further group of anephric patients, all having normal serum 25-hydroxycholecalciferol concentrations, no radioactively labelled 24,25-dihydroxycholecalciferol was formed from an injected pulse dose of [3H,14C]cholecalciferol. 5. These results indicate that in man the kidney is the major site of 24-hydroxylation of 25-hydroxycholecalciferol."}
{"id": "PMID:216523", "title": "Carcinomas and other lesions of the liver in mice ingesting organochlorine pesticides.", "content": "Carcinomas of the liver were readily induced in male and female mice given organochlorine pesticides orally. The carcinomas were predominantly hepatocellular, with a few being cholangiocellular, and varied from well differentiated to poorly differentiated to undifferentiated. They are capable of invading, metastasizing, and killing the mice. Hemangiosarcomas, leimyosarcomas, and reticulum cell sarcomas were also occasionally seen in mice receiving these chemicals. Hepatic vein thrombosis and hepatic necrosis was observed in some mice.", "contents": "Carcinomas and other lesions of the liver in mice ingesting organochlorine pesticides. Carcinomas of the liver were readily induced in male and female mice given organochlorine pesticides orally. The carcinomas were predominantly hepatocellular, with a few being cholangiocellular, and varied from well differentiated to poorly differentiated to undifferentiated. They are capable of invading, metastasizing, and killing the mice. Hemangiosarcomas, leimyosarcomas, and reticulum cell sarcomas were also occasionally seen in mice receiving these chemicals. Hepatic vein thrombosis and hepatic necrosis was observed in some mice."}
{"id": "PMID:216524", "title": "Adrenal function testing.", "content": "Glucocorticoid stimulation and suppression tests are essential to the definitive diagnosis of diseases of the hypothalamic-pituitary-adrenal axis, because they document abnormal physiologic control of hormonal secretion. Similarly, diseases of the renin-angiotensin-aldosterone axis are diagnosed by mineralocorticoid stimulation and suppression testing. [Ed. Note: See Moore TJ, Williams GH: Adrenal causes of hypertension, in this issue.] Unlike tests of glucocorticoid function, testing of the renin-angiotension-aldosterone system is more complicated, because knowledge of posture and dietary sodium are necessary to interpret the results. However, measurement of the tropic hormone renin and plasma levels of aldosterone can be accurately made, allowing precise definition of this system. Errors are most commonly encountered when dynamic tests of cortisol output are performed in patients taking medications that may interfere with the assays or with the metabolism of the administered compounds, such as dexamethasone or metyrapone. Abnormal, spurious values may also be obtained in some individuals who do not have adrenocortical hyperfunction if they are very obese or if testing is performed in a setting of clinical stress. Careful attention to these pitfalls will avoid errors and allow the clinician to arrive at the correct diagnosis.", "contents": "Adrenal function testing. Glucocorticoid stimulation and suppression tests are essential to the definitive diagnosis of diseases of the hypothalamic-pituitary-adrenal axis, because they document abnormal physiologic control of hormonal secretion. Similarly, diseases of the renin-angiotensin-aldosterone axis are diagnosed by mineralocorticoid stimulation and suppression testing. [Ed. Note: See Moore TJ, Williams GH: Adrenal causes of hypertension, in this issue.] Unlike tests of glucocorticoid function, testing of the renin-angiotension-aldosterone system is more complicated, because knowledge of posture and dietary sodium are necessary to interpret the results. However, measurement of the tropic hormone renin and plasma levels of aldosterone can be accurately made, allowing precise definition of this system. Errors are most commonly encountered when dynamic tests of cortisol output are performed in patients taking medications that may interfere with the assays or with the metabolism of the administered compounds, such as dexamethasone or metyrapone. Abnormal, spurious values may also be obtained in some individuals who do not have adrenocortical hyperfunction if they are very obese or if testing is performed in a setting of clinical stress. Careful attention to these pitfalls will avoid errors and allow the clinician to arrive at the correct diagnosis."}
{"id": "PMID:216526", "title": "Dithiocarbamate therapy for nickel dermatitis.", "content": "Increased internal exposure to nickel can cause an exacerbation of nickel contact dermatitis. Nickel ions are chelated by diethyldithiocarbamate (DDC) and thereby inactivated. An oral dose of about 1 g DDC/day was given to a patient. The nickel excretion in the urine increased about tenfold; the nickel elimination in scalp hair did not increase. The slightly negative nickel balance did not exhaust the nickel content of the organs appreciably with a dose of 1.2 g DDC/day for 2 months. At the end of this experiment patch tests with nickel sulphate were still positive though less local therapy was needed, and the cross correlation between the activity of the eczema and the nickel concentration in the urine had lost its former periodicity. It is therefore not yet possible to conclude whether or not DDC may be really of help in the very nickel hypersensitive patient by reducing the exposure to nickel originating in food and other environmental sources.", "contents": "Dithiocarbamate therapy for nickel dermatitis. Increased internal exposure to nickel can cause an exacerbation of nickel contact dermatitis. Nickel ions are chelated by diethyldithiocarbamate (DDC) and thereby inactivated. An oral dose of about 1 g DDC/day was given to a patient. The nickel excretion in the urine increased about tenfold; the nickel elimination in scalp hair did not increase. The slightly negative nickel balance did not exhaust the nickel content of the organs appreciably with a dose of 1.2 g DDC/day for 2 months. At the end of this experiment patch tests with nickel sulphate were still positive though less local therapy was needed, and the cross correlation between the activity of the eczema and the nickel concentration in the urine had lost its former periodicity. It is therefore not yet possible to conclude whether or not DDC may be really of help in the very nickel hypersensitive patient by reducing the exposure to nickel originating in food and other environmental sources."}
{"id": "PMID:216528", "title": "Enhancement of simian virus 40 uptake by permissive, semi-permissive and non-permissive cells.", "content": "The uptake of simian virus 40 (SV40) by cells that are both non-permissive for virus replication and resistant to virus infection could be enhanced markedly by infecting the cells in presence of DEAE-dextran. Virus uptake by semi-permissive and permissive cells was also enhanced by DEAE-dextran. Optimum enhancement of virus uptake occurred at 100 microgram of DEAE-dextran per ml and under the conditions employed, the polycation was not toxic to cells. The increased cellular uptake of virus may result from the uptake of virus aggregates formed in the presence of DEAE-dextran.", "contents": "Enhancement of simian virus 40 uptake by permissive, semi-permissive and non-permissive cells. The uptake of simian virus 40 (SV40) by cells that are both non-permissive for virus replication and resistant to virus infection could be enhanced markedly by infecting the cells in presence of DEAE-dextran. Virus uptake by semi-permissive and permissive cells was also enhanced by DEAE-dextran. Optimum enhancement of virus uptake occurred at 100 microgram of DEAE-dextran per ml and under the conditions employed, the polycation was not toxic to cells. The increased cellular uptake of virus may result from the uptake of virus aggregates formed in the presence of DEAE-dextran."}
{"id": "PMID:216529", "title": "Lymphocyte stimulation by herpes simplex virus (HSV) antigens. 1. Culture conditions, cell fractionation and presentation of HSV antigens.", "content": "Optimal culture conditions for rabbit lymphocytes were established. Inclusion of 2-mercaptoethanol in the medium greatly enhanced responses. Lymphocytes from the blood of HSV-immunized rabbits responded specifically in vitro to heat-killed (56 degree, 60 min) or UV-inactivated HSV preparations. A UV dose of 13,392 ergs/mm2 was the most suitable inactivating dose. Oral intramucosal injection was the most effective way of generating blood lymphocyte responses to HSV, but animals immunized in tradermally or in tramuscularly with HSV in Freund's adjuvant also produced antigen-reactive cells after five or more immunizations. There were differences in the shape of the dose-response curves to various HSV1 mutants which were probably due to differences in the production of \"stimulatory\" and inhibitory antigens. Appreciable lymphocyte stimulation could be obtained with tissue culture fluid and enveloped virus antigens. Lymphocytes from HSV1-immune animals were also responsive to HSV2 antigens.", "contents": "Lymphocyte stimulation by herpes simplex virus (HSV) antigens. 1. Culture conditions, cell fractionation and presentation of HSV antigens. Optimal culture conditions for rabbit lymphocytes were established. Inclusion of 2-mercaptoethanol in the medium greatly enhanced responses. Lymphocytes from the blood of HSV-immunized rabbits responded specifically in vitro to heat-killed (56 degree, 60 min) or UV-inactivated HSV preparations. A UV dose of 13,392 ergs/mm2 was the most suitable inactivating dose. Oral intramucosal injection was the most effective way of generating blood lymphocyte responses to HSV, but animals immunized in tradermally or in tramuscularly with HSV in Freund's adjuvant also produced antigen-reactive cells after five or more immunizations. There were differences in the shape of the dose-response curves to various HSV1 mutants which were probably due to differences in the production of \"stimulatory\" and inhibitory antigens. Appreciable lymphocyte stimulation could be obtained with tissue culture fluid and enveloped virus antigens. Lymphocytes from HSV1-immune animals were also responsive to HSV2 antigens."}
{"id": "PMID:216530", "title": "Karyotype evolution of the simian virus 40--transformed human cell line LNSV.", "content": "We have used trypsin-Wright's banding (\"GTG-banding\") to analyze the chromosome content in two sublines of the SV40-transformed human cell line LNSV, derived from fibroblasts of a patient with HPRT deficiency. Both LNSV sublines (GM-847 and \"LNSV\") were heteroploid and showed considerable numerical and structural chromosome variability. Nineteen rearranged chromosomes which were observed at high frequency have been set aside as \"marker chromosomes,\" and their probable derivation from normal human chromosomes has been described in PARIS CONFERENCE (1971) nomenclature. Heterogeneity within these uncloned sublines appears to increase with time in culture, and no evidence was found for evolution of a karyotypically stable cell population. The results are of general significance for cell genetic studies using established cell lines.", "contents": "Karyotype evolution of the simian virus 40--transformed human cell line LNSV. We have used trypsin-Wright's banding (\"GTG-banding\") to analyze the chromosome content in two sublines of the SV40-transformed human cell line LNSV, derived from fibroblasts of a patient with HPRT deficiency. Both LNSV sublines (GM-847 and \"LNSV\") were heteroploid and showed considerable numerical and structural chromosome variability. Nineteen rearranged chromosomes which were observed at high frequency have been set aside as \"marker chromosomes,\" and their probable derivation from normal human chromosomes has been described in PARIS CONFERENCE (1971) nomenclature. Heterogeneity within these uncloned sublines appears to increase with time in culture, and no evidence was found for evolution of a karyotypically stable cell population. The results are of general significance for cell genetic studies using established cell lines."}
{"id": "PMID:216531", "title": "Serial fiberoptic bronchoscopy during chemotherapy for small cell carcinoma of the lung: early detection of patients at high risk of relapse.", "content": "Serial fiberoptic bronchoscopic examinations were performed during intensive chemotherapy with a combination of drugs in 77 previously untreated patients with small cell carcinoma of the lung. Before treatment, bronchoscopic examination revealed evidence of cancer in 93 percent (70) of the 75 patients studied at that time, including 8 percent (six) in whom the tumor was not evaluable on the chest x-ray film. After therapy was initiated, 36 percent (29) of the 81 procedures performed in patients with a complete response radiographically and 62 percent (33) of the 53 bronchoscopic procedures in those with a partial response or no response showed evidence of tumor. In both of these groups, patients with abnormal findings on endoscopic examination had a much higher rate of relapsing tumor of the chest within a 12-week period. Progression of intrathoracic tumor was first detected solely by bronchoscopic examination in 22 percent (seven) of the 32 episodes of progression. In our hands, repeated fiberoptic bronchoscopic procedures during chemotherapy for small cell carcinoma have yielded information not apparent from the chest x-ray film in a significant number of patients.", "contents": "Serial fiberoptic bronchoscopy during chemotherapy for small cell carcinoma of the lung: early detection of patients at high risk of relapse. Serial fiberoptic bronchoscopic examinations were performed during intensive chemotherapy with a combination of drugs in 77 previously untreated patients with small cell carcinoma of the lung. Before treatment, bronchoscopic examination revealed evidence of cancer in 93 percent (70) of the 75 patients studied at that time, including 8 percent (six) in whom the tumor was not evaluable on the chest x-ray film. After therapy was initiated, 36 percent (29) of the 81 procedures performed in patients with a complete response radiographically and 62 percent (33) of the 53 bronchoscopic procedures in those with a partial response or no response showed evidence of tumor. In both of these groups, patients with abnormal findings on endoscopic examination had a much higher rate of relapsing tumor of the chest within a 12-week period. Progression of intrathoracic tumor was first detected solely by bronchoscopic examination in 22 percent (seven) of the 32 episodes of progression. In our hands, repeated fiberoptic bronchoscopic procedures during chemotherapy for small cell carcinoma have yielded information not apparent from the chest x-ray film in a significant number of patients."}
{"id": "PMID:216532", "title": "The significance of a cytologically negative pleural effusion in bronchogenic carcinoma.", "content": "Bronchogenic carcinoma complicated by ipsilateral cytologically positive effusion is considered unresectable. Bronchogenic carcinoma with cytologically negative effusion, even if bloody, has also been thought by many to be unresectable. Seventy-three patients with bronchogenic carcinoma and ipsilateral cytologically negative effusions were studied. Sixty-six underwent exploratory thoracotomy for staging or therapy; five had pleural biopsies and two had mediastinoscopies, all disclosing metastatic carcinoma. Four of the 73 patients (5.5 percent) had surgically resectable disease. They have remained free of disease for 3, 6, 7, and 14 years. Sixty-nine patients (94.5 percent) had unresectable carcinoma with metastases. Seventeen (94 percent) of 18 patients with bloody effusions had unresectable cancer. Carcinoma was resected in one patient with cytologically negative bloody effusion, and the patient remained free of disease during the 14-year follow-up period. Unresectability must be documented surgically in these patients to exclude those in whom curative resection can be performed.", "contents": "The significance of a cytologically negative pleural effusion in bronchogenic carcinoma. Bronchogenic carcinoma complicated by ipsilateral cytologically positive effusion is considered unresectable. Bronchogenic carcinoma with cytologically negative effusion, even if bloody, has also been thought by many to be unresectable. Seventy-three patients with bronchogenic carcinoma and ipsilateral cytologically negative effusions were studied. Sixty-six underwent exploratory thoracotomy for staging or therapy; five had pleural biopsies and two had mediastinoscopies, all disclosing metastatic carcinoma. Four of the 73 patients (5.5 percent) had surgically resectable disease. They have remained free of disease for 3, 6, 7, and 14 years. Sixty-nine patients (94.5 percent) had unresectable carcinoma with metastases. Seventeen (94 percent) of 18 patients with bloody effusions had unresectable cancer. Carcinoma was resected in one patient with cytologically negative bloody effusion, and the patient remained free of disease during the 14-year follow-up period. Unresectability must be documented surgically in these patients to exclude those in whom curative resection can be performed."}
{"id": "PMID:216537", "title": "[The problem of early diagnosis in discrete peripheral nerve lesions. Comparative study of F-wave latency and conventional motor nerve conduction velocity in healthy persons and diabetics (author's transl)].", "content": "In 71 healthy subjects and in 38 diabetics the shortest F-wave latencies were evaluated for the n.medianus, n.ulnaris, n.tibialis and n.peronaeus. The motor nerve conduction velocities calculated hereby for the upper and lower extremities were compared with the corresponding distal motor conduction velocities measured in the conventional manner. The comparison of the 2 differently defined motor conduction velocities in healthy and diabetic subjects yielded a better separation between the normal and pathological range in all 4 nerves with the method based on the F-wave latency. For the group of healthy subjects the statistical basis of a preliminary normal range of the F-wave latency was established and nomograms were provided on the basis of the 99% confidence limits which--knowing the length of the arm or leg--open the possibility to derive the corresponding motor conduction velocity.", "contents": "[The problem of early diagnosis in discrete peripheral nerve lesions. Comparative study of F-wave latency and conventional motor nerve conduction velocity in healthy persons and diabetics (author's transl)]. In 71 healthy subjects and in 38 diabetics the shortest F-wave latencies were evaluated for the n.medianus, n.ulnaris, n.tibialis and n.peronaeus. The motor nerve conduction velocities calculated hereby for the upper and lower extremities were compared with the corresponding distal motor conduction velocities measured in the conventional manner. The comparison of the 2 differently defined motor conduction velocities in healthy and diabetic subjects yielded a better separation between the normal and pathological range in all 4 nerves with the method based on the F-wave latency. For the group of healthy subjects the statistical basis of a preliminary normal range of the F-wave latency was established and nomograms were provided on the basis of the 99% confidence limits which--knowing the length of the arm or leg--open the possibility to derive the corresponding motor conduction velocity."}
{"id": "PMID:216538", "title": "Effects of thyroliberin, triiodothyronine and cyclic guanosine 3'5'-monophosphate on the volume of nuclei of thyrotropic cells in rat anterior pituitary in vitro.", "content": "Influence of TRH, T3 and cGMP on the volume of thyrotropic cells nuclei in rat pituitary in vitro has been examined. A significant increase of the volume of thyrotropic cells nuclei in the culture exposed to TRH, in another one exposed to cGMP and in the third one exposed to both TRH and cGMP together have been observed. The mean volume of cells nuclei within the group exposed to T3 was significantly lower, when compared to the control. T3 inhibited the TRH-induced increase of the volume of thyrotrophs nuclei. The obtained results suggest that the role of cGMP and T3 in the regulation of the thyrotropic cell function are independent and rather opposed. Since TRH increases the level of cAMP in the anterior pituitary, additive effect of TRH and exogenous cGMP support the assumption that both the cyclic nucleotides within the thyrotropic cell act in the same direction.", "contents": "Effects of thyroliberin, triiodothyronine and cyclic guanosine 3'5'-monophosphate on the volume of nuclei of thyrotropic cells in rat anterior pituitary in vitro. Influence of TRH, T3 and cGMP on the volume of thyrotropic cells nuclei in rat pituitary in vitro has been examined. A significant increase of the volume of thyrotropic cells nuclei in the culture exposed to TRH, in another one exposed to cGMP and in the third one exposed to both TRH and cGMP together have been observed. The mean volume of cells nuclei within the group exposed to T3 was significantly lower, when compared to the control. T3 inhibited the TRH-induced increase of the volume of thyrotrophs nuclei. The obtained results suggest that the role of cGMP and T3 in the regulation of the thyrotropic cell function are independent and rather opposed. Since TRH increases the level of cAMP in the anterior pituitary, additive effect of TRH and exogenous cGMP support the assumption that both the cyclic nucleotides within the thyrotropic cell act in the same direction."}
{"id": "PMID:216539", "title": "The neurohypophysial vasopressin content as influenced by modified cholinergic or adrenergic transmission during long-term dehydration in the white rat.", "content": "In rats dehydrated up to 12 days the neurohypophysial vasopressin content was determined by Deka\u0144ski's method. Carbamylcholine inhibited somewhat the vasopressin depletion in the neurohypophysis, but not earlier than under severe dehydration (8th and 12th day). A single dose of atropine given 24 h prior to sacrifice to not dehydrated animals resulted in a diminution of the vasopressin content in the neurohypophysis; in animals dehydrated for four days and parallely atropinized the decrease of the neurohypophyseal vasopressin content was, on the contrary, considerably inhibited. Under severe dehydration, the treatment with atropine did not change the vasopressin stores in the neural lobe. Phenoxybenzamine inhibited the vasopressin depletion in the neural lobe following four days of dehydration. Under severe dehydration, amphetamine potentiated the effect of osmoreceptor stimulation. It is supposed that impulses of osmoreceptor origin are of some importance in determining the vasopressin release following changes of cholinergic or adrenergic transmission.", "contents": "The neurohypophysial vasopressin content as influenced by modified cholinergic or adrenergic transmission during long-term dehydration in the white rat. In rats dehydrated up to 12 days the neurohypophysial vasopressin content was determined by Deka\u0144ski's method. Carbamylcholine inhibited somewhat the vasopressin depletion in the neurohypophysis, but not earlier than under severe dehydration (8th and 12th day). A single dose of atropine given 24 h prior to sacrifice to not dehydrated animals resulted in a diminution of the vasopressin content in the neurohypophysis; in animals dehydrated for four days and parallely atropinized the decrease of the neurohypophyseal vasopressin content was, on the contrary, considerably inhibited. Under severe dehydration, the treatment with atropine did not change the vasopressin stores in the neural lobe. Phenoxybenzamine inhibited the vasopressin depletion in the neural lobe following four days of dehydration. Under severe dehydration, amphetamine potentiated the effect of osmoreceptor stimulation. It is supposed that impulses of osmoreceptor origin are of some importance in determining the vasopressin release following changes of cholinergic or adrenergic transmission."}
{"id": "PMID:216540", "title": "[ACTH-, glucose- and lactate-content of swine plasma during insulin-induced hypoglycemia].", "content": "The present investigation was undertaken to determine the content of ACTH, glucose and lactate in plasma of 4 pigs (body weight 82--118 kg) during a circadian period and during an insulin hypoglycemia test using 1 IU/kg in 3 pigs (body weight 96--118 kg) and 4 pigs (body weight 20--30 kg). The plasma ACTH level at rest was 57 +/- 27 pg/ml (Mean +/- SE) for all samples in all animals during a circadian period. Significant diurnal changes were not observed. During insulin-induced hypoglycaemia plasma ACTH rose from a mean (+/- SE) basal level of 35 +/- 15 to a maximum of 673 +/- 100 pg/ml at 60 min in heavier pigs and in lighter pigs to 395 +/- 153 at 30 min and 403 +/- 145 pg/ml at 120 min. Initial ACTH responses were evident 30 min (heavier pigs) and between 0 and 15 min (lighter pigs) after insulin administration. Plasma glucose decreased from a mean (+/- SE) basal level of 80 +/- 10 to a minimum of 6 +/- 1 mg/100 ml at 60 min (heavier pigs) and from 88 +/- 3 to 16 +/- 4 mg/100 ml at 60 min (lighter pigs). After its minimum level the glucose concentration showed a slower increment in the heavier pigs as compared to lighter animals. Plasma lactate rose from a mean (+/- SE) basal level of 19 +/- 10 to a maximum of 76 +/- 42 mg/100 ml at 120 min (heavier pigs) and from 12 +/- 3 to 37 +/- 16 mg/100 ml at 150 min (lighter group). In accordance with the changes in the blood plasma levels of ACTH, glucose and lactate, the clinical symptoms of hypoglycaemia in heavier pigs were more intensive.", "contents": "[ACTH-, glucose- and lactate-content of swine plasma during insulin-induced hypoglycemia]. The present investigation was undertaken to determine the content of ACTH, glucose and lactate in plasma of 4 pigs (body weight 82--118 kg) during a circadian period and during an insulin hypoglycemia test using 1 IU/kg in 3 pigs (body weight 96--118 kg) and 4 pigs (body weight 20--30 kg). The plasma ACTH level at rest was 57 +/- 27 pg/ml (Mean +/- SE) for all samples in all animals during a circadian period. Significant diurnal changes were not observed. During insulin-induced hypoglycaemia plasma ACTH rose from a mean (+/- SE) basal level of 35 +/- 15 to a maximum of 673 +/- 100 pg/ml at 60 min in heavier pigs and in lighter pigs to 395 +/- 153 at 30 min and 403 +/- 145 pg/ml at 120 min. Initial ACTH responses were evident 30 min (heavier pigs) and between 0 and 15 min (lighter pigs) after insulin administration. Plasma glucose decreased from a mean (+/- SE) basal level of 80 +/- 10 to a minimum of 6 +/- 1 mg/100 ml at 60 min (heavier pigs) and from 88 +/- 3 to 16 +/- 4 mg/100 ml at 60 min (lighter pigs). After its minimum level the glucose concentration showed a slower increment in the heavier pigs as compared to lighter animals. Plasma lactate rose from a mean (+/- SE) basal level of 19 +/- 10 to a maximum of 76 +/- 42 mg/100 ml at 120 min (heavier pigs) and from 12 +/- 3 to 37 +/- 16 mg/100 ml at 150 min (lighter group). In accordance with the changes in the blood plasma levels of ACTH, glucose and lactate, the clinical symptoms of hypoglycaemia in heavier pigs were more intensive."}
{"id": "PMID:216541", "title": "[Daily cyclic changes in thyroid cAMP in chickens (Gallus domesticus)].", "content": "48 White Leghorn cockereles (age: 4 weeks) were examined for daily alterations of thyroidal and plasma cAMP-concentrations by means of a radioimmunoassay. In the morning and in the evening the thyroidal cAMP-concentration was elevated. This elevation was accompanied by a decrease of thyroid-weight. Alterations of blood cAMP-concentration were without recognizable effect on thyroid function. It is assumed that mediated by the effect of the second messenger more thyreoglobulin is released at these times.", "contents": "[Daily cyclic changes in thyroid cAMP in chickens (Gallus domesticus)]. 48 White Leghorn cockereles (age: 4 weeks) were examined for daily alterations of thyroidal and plasma cAMP-concentrations by means of a radioimmunoassay. In the morning and in the evening the thyroidal cAMP-concentration was elevated. This elevation was accompanied by a decrease of thyroid-weight. Alterations of blood cAMP-concentration were without recognizable effect on thyroid function. It is assumed that mediated by the effect of the second messenger more thyreoglobulin is released at these times."}
{"id": "PMID:216542", "title": "Benign tumors of oesophagus: value of endoscopy.", "content": "Endoscopic examination carried out in 20,000 patients allowed 7 benign tumors of the oesophagus to be detected. Four of them were intramural tumors corresponding to leiomyomas. Guided biopsies are not sufficient to assure an accurate diagnosis, but a mucosal lesion, particularly a carcinoma, should be ruled out. Endoscopic resection of the 3 intraluminal tumours was performed without incidents, allowing an accurate histologic diagnosis and a reasonable therapeutic approach. Endoscopic supervision is necessary in case of epithelial tumors.", "contents": "Benign tumors of oesophagus: value of endoscopy. Endoscopic examination carried out in 20,000 patients allowed 7 benign tumors of the oesophagus to be detected. Four of them were intramural tumors corresponding to leiomyomas. Guided biopsies are not sufficient to assure an accurate diagnosis, but a mucosal lesion, particularly a carcinoma, should be ruled out. Endoscopic resection of the 3 intraluminal tumours was performed without incidents, allowing an accurate histologic diagnosis and a reasonable therapeutic approach. Endoscopic supervision is necessary in case of epithelial tumors."}
{"id": "PMID:216543", "title": "Epileptogenic agents applied to trigeminal ganglia: absence of neuronal hyperexcitability.", "content": "Chronic application of alumina cream to the trigeminal ganglion in 10 cats failed to produce a long-lasting behavioral syndrome of facial dysesthesia. Histologic and electron microscopic analysis demonstrated morphologic similarities between these ganglia and primate neocortical alumina cream epileptic foci. None of 87 ganglia neurons recorded extracellularly exhibited evidence of intrinsic hyperexcitability, i.e., abnormal spontaneous or physiologically evoked activity or any significant differences in threshold of responses to antidromic or orthodromic electrical stimulation, compared to 67 normal ganglion cells. Furthermore, topical application of penicillin to normal ganglia failed to produce abnormal activity in 42 neurons tested. These data suggest that neuronal somata lacking either dendrites or postsynaptic membranes, or both, do not develop abnormal firing behavior when challenged with these two epileptogenic agents.", "contents": "Epileptogenic agents applied to trigeminal ganglia: absence of neuronal hyperexcitability. Chronic application of alumina cream to the trigeminal ganglion in 10 cats failed to produce a long-lasting behavioral syndrome of facial dysesthesia. Histologic and electron microscopic analysis demonstrated morphologic similarities between these ganglia and primate neocortical alumina cream epileptic foci. None of 87 ganglia neurons recorded extracellularly exhibited evidence of intrinsic hyperexcitability, i.e., abnormal spontaneous or physiologically evoked activity or any significant differences in threshold of responses to antidromic or orthodromic electrical stimulation, compared to 67 normal ganglion cells. Furthermore, topical application of penicillin to normal ganglia failed to produce abnormal activity in 42 neurons tested. These data suggest that neuronal somata lacking either dendrites or postsynaptic membranes, or both, do not develop abnormal firing behavior when challenged with these two epileptogenic agents."}
{"id": "PMID:216544", "title": "Enhancement of alcohol withdrawal seizures with 6-hydroxydopamine.", "content": "The relationship between central catecholamine neurons and alcohol withdrawal seizures was studied in rats pretreated with 6-hydroxydopamine to selectively destroy the central catecholamine nerve terminals. The alteration of alcohol withdrawal seizures was manifested by (1) a higher percentage of the rats developing the seizures, (2) an earlier onset of seizures, and (3) a greater severity of seizure activity. Seizure status was exhibited in 25% of the 6-hydroxydopamine-treated rats.", "contents": "Enhancement of alcohol withdrawal seizures with 6-hydroxydopamine. The relationship between central catecholamine neurons and alcohol withdrawal seizures was studied in rats pretreated with 6-hydroxydopamine to selectively destroy the central catecholamine nerve terminals. The alteration of alcohol withdrawal seizures was manifested by (1) a higher percentage of the rats developing the seizures, (2) an earlier onset of seizures, and (3) a greater severity of seizure activity. Seizure status was exhibited in 25% of the 6-hydroxydopamine-treated rats."}
{"id": "PMID:216545", "title": "Preferential charging of tRNA-Met-f in Escherichia coli K12.", "content": "The charging of tRNA-Met-f and tRNA-Met-m in vivo and in vitro and initiation of polysomes during methionine limitation were studied in two strains of Escherichia coli K12. In the wild-type strain the distribution of polysomes as well as the kinetic parameters of methionyl-tRNA synthetase indicate preferential acylation of tRNA-Met-f. This preferential charging of tRNAM-et-f does not take place in a mutant strain which is also defective in initiation of polysomes during methionine limitation.", "contents": "Preferential charging of tRNA-Met-f in Escherichia coli K12. The charging of tRNA-Met-f and tRNA-Met-m in vivo and in vitro and initiation of polysomes during methionine limitation were studied in two strains of Escherichia coli K12. In the wild-type strain the distribution of polysomes as well as the kinetic parameters of methionyl-tRNA synthetase indicate preferential acylation of tRNA-Met-f. This preferential charging of tRNAM-et-f does not take place in a mutant strain which is also defective in initiation of polysomes during methionine limitation."}
{"id": "PMID:216547", "title": "Synthesis and breakdown of pppA2'p5'A2'p5'A and transient inhibiton of protein synthesis in extracts from interferon-treated and control cells.", "content": "Incubation of the mouse L-cell-free system with a concentration of pppA2'p5'A2'p5'A [(2'-5')An] just sufficient to inhibit protein synthesis results in formation of a high-molecular-weight, heatlabile inhibitor and enhanced ribonuclease activity and in the rapid breakdown of (2'-5')An to ATP. The (2'-5')An-enhanced ribonuclease activity is also unstable and in the absence of a (2'-5')-An-regenerating system inhibiton of protein synthesis is transient. Although interferon treatment enhances the synthesis of (2'-5')An, the rates of degradation of (2'-5')An and levels of activatible nuclease are similar in extracts prepared from control or interferon-treated cells. Interestingly, the sensitivity of different cell-free systems to (2'-5')An, varies with the source of the cell-free systems and with the methods used in their preparation. There is, however, no obvious correlation between the sensitivities of the system and the rate of breakdown of (2'-5')An. The significance of these results is discussed in relation to a possible control function for the (2'-5')An system in both interferon-treated and control cells.", "contents": "Synthesis and breakdown of pppA2'p5'A2'p5'A and transient inhibiton of protein synthesis in extracts from interferon-treated and control cells. Incubation of the mouse L-cell-free system with a concentration of pppA2'p5'A2'p5'A [(2'-5')An] just sufficient to inhibit protein synthesis results in formation of a high-molecular-weight, heatlabile inhibitor and enhanced ribonuclease activity and in the rapid breakdown of (2'-5')An to ATP. The (2'-5')An-enhanced ribonuclease activity is also unstable and in the absence of a (2'-5')-An-regenerating system inhibiton of protein synthesis is transient. Although interferon treatment enhances the synthesis of (2'-5')An, the rates of degradation of (2'-5')An and levels of activatible nuclease are similar in extracts prepared from control or interferon-treated cells. Interestingly, the sensitivity of different cell-free systems to (2'-5')An, varies with the source of the cell-free systems and with the methods used in their preparation. There is, however, no obvious correlation between the sensitivities of the system and the rate of breakdown of (2'-5')An. The significance of these results is discussed in relation to a possible control function for the (2'-5')An system in both interferon-treated and control cells."}
{"id": "PMID:216550", "title": "Comparative experimental study of myocardial energy metabolism during ventricular workload induced by chronic stenoses of ascendent aorta and pulmonary artery.", "content": "In this paper, an attempt was made to describe the alterations of the myocardial energy metabolism following moderate stenoses of aorta or pulmonary artery. Biochemical investigations regarding the main high energy phosphates and a large series of dehydrogenases in the myocardium of the overloaded ventricles have revealed the following facts: (1) the myocardial CP-CPK system appears to be more labile than the myocardial AMP-ATP system in response to a ventricular overload; (2) the changes in the amounts of myocardial high energy phosphates seem to be more important in the right chronic cardiac overload than in the left one; (3) before the overloaded ventricle becomes insufficient, the myocardial dehydrogenase system elicits no alteration, suggesting that the oxidative phosphorylation is not affected; (4) there is a closer relationship between the coronary flow and pressure and the myocardial energy metabolism than that existing between this metabolism and the tension of the myocardial fibres following a persistent increase in the systemic arterial resistance.", "contents": "Comparative experimental study of myocardial energy metabolism during ventricular workload induced by chronic stenoses of ascendent aorta and pulmonary artery. In this paper, an attempt was made to describe the alterations of the myocardial energy metabolism following moderate stenoses of aorta or pulmonary artery. Biochemical investigations regarding the main high energy phosphates and a large series of dehydrogenases in the myocardium of the overloaded ventricles have revealed the following facts: (1) the myocardial CP-CPK system appears to be more labile than the myocardial AMP-ATP system in response to a ventricular overload; (2) the changes in the amounts of myocardial high energy phosphates seem to be more important in the right chronic cardiac overload than in the left one; (3) before the overloaded ventricle becomes insufficient, the myocardial dehydrogenase system elicits no alteration, suggesting that the oxidative phosphorylation is not affected; (4) there is a closer relationship between the coronary flow and pressure and the myocardial energy metabolism than that existing between this metabolism and the tension of the myocardial fibres following a persistent increase in the systemic arterial resistance."}
{"id": "PMID:216551", "title": "Measurements of total and regional tumor blood flow and organ blood flow using 99Tcm labelled microspheres. An experimental study in rats.", "content": "Cardiac output, regional tissue and arterial tumor blood flow were studied in rats, with 99Tcm labelled microspheres using a reference sample simultaneously drawn as the spheres were injected. Both cardiac output and regional blood flow can be estimated in absolute values (ml X min-1 X g-1). Cardiac output and normal tissue blood flow were not affected by tumor growth in the liver or subcutaneously. In small tumors total blood flow was inversely proportional to tumor size, a finding similar in all 3 tumors studied. A relation found in liver as well as in subcutaneously implanted tumors. Blood flow in subcutaneous tumors was greater than muscle or skin blood flow. BP sarcoma had higher blood flow than the hepatoma and the adenocarcinoma. In big tumors the peripheral blood flow was larger than that in the centre of the tumor.", "contents": "Measurements of total and regional tumor blood flow and organ blood flow using 99Tcm labelled microspheres. An experimental study in rats. Cardiac output, regional tissue and arterial tumor blood flow were studied in rats, with 99Tcm labelled microspheres using a reference sample simultaneously drawn as the spheres were injected. Both cardiac output and regional blood flow can be estimated in absolute values (ml X min-1 X g-1). Cardiac output and normal tissue blood flow were not affected by tumor growth in the liver or subcutaneously. In small tumors total blood flow was inversely proportional to tumor size, a finding similar in all 3 tumors studied. A relation found in liver as well as in subcutaneously implanted tumors. Blood flow in subcutaneous tumors was greater than muscle or skin blood flow. BP sarcoma had higher blood flow than the hepatoma and the adenocarcinoma. In big tumors the peripheral blood flow was larger than that in the centre of the tumor."}
{"id": "PMID:216552", "title": "Incidence and natural history of renal stone disease and its relationship to calcium metabolism.", "content": "In three different general health surveys, including more than 17,000 individuals, the prevalence of renal stone disease was over 10% of all males and 3% of all females. Stones are thus far more common in the population than is generally appreciated from hospital statistics. Each year approximately 1% of the entire adult male population experiences renal stones. This figure appears to increase rapidly and is now at least twice as high as only 20 years ago. Stone formers as a group had a raised urinary excretion of calcium, but were not particularly accumulated in the upper part of the normal urinary calcium distribution. This pattern was generally caused by an intestinal hyperabsorption of calcium, apparently not dependent on the action of parathyroid hormone. The prevalence of stone disease was closely related to the urinary calcium output.", "contents": "Incidence and natural history of renal stone disease and its relationship to calcium metabolism. In three different general health surveys, including more than 17,000 individuals, the prevalence of renal stone disease was over 10% of all males and 3% of all females. Stones are thus far more common in the population than is generally appreciated from hospital statistics. Each year approximately 1% of the entire adult male population experiences renal stones. This figure appears to increase rapidly and is now at least twice as high as only 20 years ago. Stone formers as a group had a raised urinary excretion of calcium, but were not particularly accumulated in the upper part of the normal urinary calcium distribution. This pattern was generally caused by an intestinal hyperabsorption of calcium, apparently not dependent on the action of parathyroid hormone. The prevalence of stone disease was closely related to the urinary calcium output."}
{"id": "PMID:216557", "title": "alpha-Adrenergic modulation of hypothalamic self-stimulation: effects of phenoxybenzamine, yohimbine, dexamphetamine and their interactions with clonidine.", "content": "The alpha-adrenoceptor agonist clonidine (12.5--50.0 microgram/kg) produced a dose-dependent increase in the latency to initiate lateral hypothalamic stimulation. The insurmountable postsynaptic alpha-adrenoceptor antagonist phenoxybenzamine (0.2-0.8 mg/kg) had no effect on self-stimulation by itself, but potentiated the inhibitory effects of clonidine. The fact that the concurrent escape behavior to the intracranial stimulation was unchanged by either clonidine or the phenoxybenzamine-clonidine combination suggests that the inhibition is specific to the rewarding component of hypothalamic stimulation. Yohimbine (0.5--2.0 mg/kg) produced a dose-dependent increase in both response latencies. This lack of behavioral specificity may reflect yohimbine's wide range of pharmacological activity, Dexamphetamine (0.25--0.50 mg/kg) reversed clonidine's inhibition of self-stimulation reward in a specific and dose-dependent fashion. This reversal could be blocked by previous inhibition of catecholamine synthesis with alpha-methyl-p-tyrosine. These data support the concept that the alpha-adrenoceptors play a critical role in the modulation of hypothalamic self-stimulation reward. They further suggest that the inhibitory effects of clonidine on self-stimulation reward represent an agonist effect on presynaptic alpha-adrenoceptors.", "contents": "alpha-Adrenergic modulation of hypothalamic self-stimulation: effects of phenoxybenzamine, yohimbine, dexamphetamine and their interactions with clonidine. The alpha-adrenoceptor agonist clonidine (12.5--50.0 microgram/kg) produced a dose-dependent increase in the latency to initiate lateral hypothalamic stimulation. The insurmountable postsynaptic alpha-adrenoceptor antagonist phenoxybenzamine (0.2-0.8 mg/kg) had no effect on self-stimulation by itself, but potentiated the inhibitory effects of clonidine. The fact that the concurrent escape behavior to the intracranial stimulation was unchanged by either clonidine or the phenoxybenzamine-clonidine combination suggests that the inhibition is specific to the rewarding component of hypothalamic stimulation. Yohimbine (0.5--2.0 mg/kg) produced a dose-dependent increase in both response latencies. This lack of behavioral specificity may reflect yohimbine's wide range of pharmacological activity, Dexamphetamine (0.25--0.50 mg/kg) reversed clonidine's inhibition of self-stimulation reward in a specific and dose-dependent fashion. This reversal could be blocked by previous inhibition of catecholamine synthesis with alpha-methyl-p-tyrosine. These data support the concept that the alpha-adrenoceptors play a critical role in the modulation of hypothalamic self-stimulation reward. They further suggest that the inhibitory effects of clonidine on self-stimulation reward represent an agonist effect on presynaptic alpha-adrenoceptors."}
{"id": "PMID:216558", "title": "Variations in endogenous phosphodiesterase activator content of rat aorta.", "content": "The variations with age and blood pressure in the cyclic nucleotide phosphodiesterase activator content of rat aorta were studied. Activator content increased with age and was less in mineralocorticoid-hypertensive than in control rats. These variations were more pronounced in the particulate than in the soluble fraction of aorta. The data do not demonstrate any relationship between the activator level and blood pressure, but they suggest that the activator may modulate cyclic nucleotide metabolism in rat aorta.", "contents": "Variations in endogenous phosphodiesterase activator content of rat aorta. The variations with age and blood pressure in the cyclic nucleotide phosphodiesterase activator content of rat aorta were studied. Activator content increased with age and was less in mineralocorticoid-hypertensive than in control rats. These variations were more pronounced in the particulate than in the soluble fraction of aorta. The data do not demonstrate any relationship between the activator level and blood pressure, but they suggest that the activator may modulate cyclic nucleotide metabolism in rat aorta."}
{"id": "PMID:216559", "title": "Effect of extracellular Na on isoproterenol-induced cAMP levels in depolarized uterus.", "content": "In the present study, the absence of a quantitative correlation between isoproterenol induced relaxation of uterine strips and tissue cAMP levels was demonstrated by using three depolarizing media: 127 mM KCl (0 NaCl), 47.5 mM KCl (NaCl), and 47.5 mM KCl (80 mM NaCl). While the degree of relaxation by isoproterenol was similar in all three media, isoproterenol (10(-4)M) increased cAMP by 100% in Na+ free depolarizing media, by 337% in Na+ containing depolarizing medium and by 600% in normal non-depolarizing medium. After pretreatment of the tissue with 10(-5) M D-600, 10(-4) M isoproterenol increased cAMP levels by 600% in all three depolarzing media. Studies using 10(-8) M isoproterenol produced qualitatively similar results. cGMP levels did not change significantly in any of the above studies. Na+ appears to be producing its effect on isoproterenol induced increase in cAMP levels indirectly by reducing the increase in intracellular Ca2+ concentration known to occur with depolarization.", "contents": "Effect of extracellular Na on isoproterenol-induced cAMP levels in depolarized uterus. In the present study, the absence of a quantitative correlation between isoproterenol induced relaxation of uterine strips and tissue cAMP levels was demonstrated by using three depolarizing media: 127 mM KCl (0 NaCl), 47.5 mM KCl (NaCl), and 47.5 mM KCl (80 mM NaCl). While the degree of relaxation by isoproterenol was similar in all three media, isoproterenol (10(-4)M) increased cAMP by 100% in Na+ free depolarizing media, by 337% in Na+ containing depolarizing medium and by 600% in normal non-depolarizing medium. After pretreatment of the tissue with 10(-5) M D-600, 10(-4) M isoproterenol increased cAMP levels by 600% in all three depolarzing media. Studies using 10(-8) M isoproterenol produced qualitatively similar results. cGMP levels did not change significantly in any of the above studies. Na+ appears to be producing its effect on isoproterenol induced increase in cAMP levels indirectly by reducing the increase in intracellular Ca2+ concentration known to occur with depolarization."}
{"id": "PMID:216568", "title": "Effect of dibutyryl cyclic AMP and analogs on the rate of contractions of myocytes in culture.", "content": "2O, 6N-butyryl, 3', 5'-cyclic monophosphate (dibu cAMP) when added to fetal rat heart cells in culture inhibits myocyte contraction. This inhibition is 100, 84 and 51% complete when the dibu cAMP concentration used is 2, 0.2 and 0.02 mM, respectively. The potency of dibu cAMP derivatives in myocyte contraction inhibition follows the order, dibu cAMP greater than 6N-bu cAMP greater than 2O-bu cAMP = AMP greater than butyrate. The inhibition caused by the first three chemicals is greater than 70%.", "contents": "Effect of dibutyryl cyclic AMP and analogs on the rate of contractions of myocytes in culture. 2O, 6N-butyryl, 3', 5'-cyclic monophosphate (dibu cAMP) when added to fetal rat heart cells in culture inhibits myocyte contraction. This inhibition is 100, 84 and 51% complete when the dibu cAMP concentration used is 2, 0.2 and 0.02 mM, respectively. The potency of dibu cAMP derivatives in myocyte contraction inhibition follows the order, dibu cAMP greater than 6N-bu cAMP greater than 2O-bu cAMP = AMP greater than butyrate. The inhibition caused by the first three chemicals is greater than 70%."}
{"id": "PMID:216567", "title": "Acetylcholine synthesis and its dependence on nervous activity.", "content": "The findings discussed in this paper mainly derived from studies on salivary glands, serving as model organs, indicate that the capacity to form the neurotransmitter acetylcholine, as judged by the activity of choline acetyltransferase, is influenced by the traffic of nerve impulses, as a long term effect. In the glands, choline acetyltransferase seems to be exclusively localized to the cholinergic nerves. In the postganglionic parasympathetic nerves of the glands, the activity of choline acetyltransferase decreases when the flow of secretory impulses in these nerves is abolished or reduced either by isolating the nerves from the central nervous system, surgically or pharmacologically, or by diminishing the reflex activation of the glands from the mouth. The opposite occurs when the reflex activation of the salivary glands is enhanced, i.e. the activity of choline acetyltransferase increases. Observations on various other organs are quoted in support of the view that the traffic of nerve impulses is of importance for the activity of the enzyme. An increase in choline acetyltransferase activity also occurs in some salivary glands after sympathetic denervation. This puzzling observation is discussed in relation to impulse traffic. Increased nerve impulse traffic and collateral sprouting seem to be responsible for the rapid restitution of choline acetyltransferase activity from a low level in an organ partially deprived of its cholinergic nerve supply.", "contents": "Acetylcholine synthesis and its dependence on nervous activity. The findings discussed in this paper mainly derived from studies on salivary glands, serving as model organs, indicate that the capacity to form the neurotransmitter acetylcholine, as judged by the activity of choline acetyltransferase, is influenced by the traffic of nerve impulses, as a long term effect. In the glands, choline acetyltransferase seems to be exclusively localized to the cholinergic nerves. In the postganglionic parasympathetic nerves of the glands, the activity of choline acetyltransferase decreases when the flow of secretory impulses in these nerves is abolished or reduced either by isolating the nerves from the central nervous system, surgically or pharmacologically, or by diminishing the reflex activation of the glands from the mouth. The opposite occurs when the reflex activation of the salivary glands is enhanced, i.e. the activity of choline acetyltransferase increases. Observations on various other organs are quoted in support of the view that the traffic of nerve impulses is of importance for the activity of the enzyme. An increase in choline acetyltransferase activity also occurs in some salivary glands after sympathetic denervation. This puzzling observation is discussed in relation to impulse traffic. Increased nerve impulse traffic and collateral sprouting seem to be responsible for the rapid restitution of choline acetyltransferase activity from a low level in an organ partially deprived of its cholinergic nerve supply."}
{"id": "PMID:216569", "title": "Correlation between 3',5', c-AMP levels and thyrotropin in separated rat pituitary thyrotropic cells.", "content": "The correlation between 3',5', c-AMP levels, TSH content and secretion of separated thyrotropic cells was studied. Incubation of the separated cells with 1, 10 and 100 ng of TRH does not change the 3',5',c-AMP levels, despite the significant rises of the TSH level. Dibutyryl c-AMP causes rise in TSH content, with no indication of its secretion. PGE2 10(-5) increased 3'5',c-AMP levels with no change in the content or secretion of TSH in separated thyrotropic cells.", "contents": "Correlation between 3',5', c-AMP levels and thyrotropin in separated rat pituitary thyrotropic cells. The correlation between 3',5', c-AMP levels, TSH content and secretion of separated thyrotropic cells was studied. Incubation of the separated cells with 1, 10 and 100 ng of TRH does not change the 3',5',c-AMP levels, despite the significant rises of the TSH level. Dibutyryl c-AMP causes rise in TSH content, with no indication of its secretion. PGE2 10(-5) increased 3'5',c-AMP levels with no change in the content or secretion of TSH in separated thyrotropic cells."}
{"id": "PMID:216570", "title": "Cyclic AMP is a likely mediator of ovulation in the tsetse fly.", "content": "Ovulation in tsetse flies is normally induced by mating, but virgins can be stimulated to ovulate with an injection of dibutyryl cyclic AMP, cholera toxin (a cyclic AMP generator), or aminophylline (a phosphodiesterase inhibitor). Thus, elevation of cyclic AMP is a likely link in the events leading to ovulation.", "contents": "Cyclic AMP is a likely mediator of ovulation in the tsetse fly. Ovulation in tsetse flies is normally induced by mating, but virgins can be stimulated to ovulate with an injection of dibutyryl cyclic AMP, cholera toxin (a cyclic AMP generator), or aminophylline (a phosphodiesterase inhibitor). Thus, elevation of cyclic AMP is a likely link in the events leading to ovulation."}
{"id": "PMID:216571", "title": "Naloxone and intestinal motility.", "content": "It was supposed that the inhibition of intestinal peristalsis seen in animals and humans after abdominal surgery might be related to the release of endorphins, endogenous opiate receptor agonists, caused by the surgical stress and pain. However, naloxone, a potent morphine and endorphin antagonist, failed to block this peristaltic inhibition in rats, which leaves the mechanism of this inhibition, and thus the function of intestinal endorphins, still very much in doubt.", "contents": "Naloxone and intestinal motility. It was supposed that the inhibition of intestinal peristalsis seen in animals and humans after abdominal surgery might be related to the release of endorphins, endogenous opiate receptor agonists, caused by the surgical stress and pain. However, naloxone, a potent morphine and endorphin antagonist, failed to block this peristaltic inhibition in rats, which leaves the mechanism of this inhibition, and thus the function of intestinal endorphins, still very much in doubt."}
{"id": "PMID:216573", "title": "Cadmium effects on bone and dental tissues of rats in acute and subacute poisoning.", "content": "Injection of cadmium chloride to rats fed by normal calcium diet induced distrubances of tibia and incisor hard tissues metabolism. It is suggested that there may be the possibility of direct cadmium actions on those hard tissues metabolisms.", "contents": "Cadmium effects on bone and dental tissues of rats in acute and subacute poisoning. Injection of cadmium chloride to rats fed by normal calcium diet induced distrubances of tibia and incisor hard tissues metabolism. It is suggested that there may be the possibility of direct cadmium actions on those hard tissues metabolisms."}
{"id": "PMID:216572", "title": "Can the binding of GABA, glycine and beta-alanine to synaptic receptors be determined in the presence of a physiological concentration of Na+?", "content": "Bicuculline- and strychnine-sensitive components of the binding of GABA, glycine and beta-alanine, which can be demonstrated in the presence of a physiological concentration of Na+, might be related to synaptic receptors.", "contents": "Can the binding of GABA, glycine and beta-alanine to synaptic receptors be determined in the presence of a physiological concentration of Na+? Bicuculline- and strychnine-sensitive components of the binding of GABA, glycine and beta-alanine, which can be demonstrated in the presence of a physiological concentration of Na+, might be related to synaptic receptors."}
{"id": "PMID:216574", "title": "Influence of dithiocarb on the biliary excretion of paracetamol and bilirubin in rats.", "content": "In bile-fistula rats, the biliary elimination of conjugated paracetamol and conjugated bilirubin is diminished by simultaneous administration of dithiocarb. This dithiocarb effect could be the result of the interference with the glucuronidation of the compounds.", "contents": "Influence of dithiocarb on the biliary excretion of paracetamol and bilirubin in rats. In bile-fistula rats, the biliary elimination of conjugated paracetamol and conjugated bilirubin is diminished by simultaneous administration of dithiocarb. This dithiocarb effect could be the result of the interference with the glucuronidation of the compounds."}
{"id": "PMID:216575", "title": "Relationships between neural crest cells and catecholamine in suckling mice.", "content": "In suckling mice injected i.p. with a 27 mg/kg dose of L-hydrochloric acid isoproterenol, multiple neural crest tumors developed and cell death of neural crest cells occurred. It is speculated that neural crest derivatives may be beta-receptor cells and contain regulatory units of neurotransmission mediated through cyclic AMP.", "contents": "Relationships between neural crest cells and catecholamine in suckling mice. In suckling mice injected i.p. with a 27 mg/kg dose of L-hydrochloric acid isoproterenol, multiple neural crest tumors developed and cell death of neural crest cells occurred. It is speculated that neural crest derivatives may be beta-receptor cells and contain regulatory units of neurotransmission mediated through cyclic AMP."}
{"id": "PMID:216576", "title": "[Azotized emetine analogues: synthesis and evaluation of the anti-amebic and anti-tumoral action of aza-3 emetine and attempted synthesis of aza-2 emetine].", "content": "The synthesis of the N,N-bis-(acetylhomoveratrylamido)-1-hydroxymethyl and 1-carboxypropylamines (III a) and (III b) is described. Until now, these molecules could not been cyclized to the corresponding isoquinoline compounds. An attempted synthesis of 3-azaemetine by condensing homoveratrylamine with acetonedicarboxylic acid or its esters did not yield the expected diamide (XIV). However, by subjecting 1,3-bis-(1,2,3,4-tetrahydro-6,7-dimethoxy-1-isoquinolyl)acetone (XV) to a reducing aminoalkylation, one obtained the corresponding ethylamino derivative (XVI) which could be cyclized through Mannich reaction to give 3-azaemetine. The pharmacological screening showed 3-azaemetine to be less toxic than emetine in the mouse and without antiamebic and antitumor activity against P 388 Leukaemia in the mouse (25).", "contents": "[Azotized emetine analogues: synthesis and evaluation of the anti-amebic and anti-tumoral action of aza-3 emetine and attempted synthesis of aza-2 emetine]. The synthesis of the N,N-bis-(acetylhomoveratrylamido)-1-hydroxymethyl and 1-carboxypropylamines (III a) and (III b) is described. Until now, these molecules could not been cyclized to the corresponding isoquinoline compounds. An attempted synthesis of 3-azaemetine by condensing homoveratrylamine with acetonedicarboxylic acid or its esters did not yield the expected diamide (XIV). However, by subjecting 1,3-bis-(1,2,3,4-tetrahydro-6,7-dimethoxy-1-isoquinolyl)acetone (XV) to a reducing aminoalkylation, one obtained the corresponding ethylamino derivative (XVI) which could be cyclized through Mannich reaction to give 3-azaemetine. The pharmacological screening showed 3-azaemetine to be less toxic than emetine in the mouse and without antiamebic and antitumor activity against P 388 Leukaemia in the mouse (25)."}
{"id": "PMID:216589", "title": "Distribution of Na+-pump sites in transporting epithelia.", "content": "There are three techniques for the localization of intraepithelial Na+, K+-ATPase (usually equated with the Na+-pump) that offer reasonable specificity and resolution: the nitrophenylphosphatase assay of Ernst, the immunoferritin procedure of Kyte, and the radioautographic localization of tritiated ouabain as developed by Stirling. These have now been applied to a wide range of epithelia covering the four classes of interest here: isotonic and hypertonic absorbers and isotonic and hypertonic secretors. A review of published results reveals that in every case (except for the choroid plexus) the enzyme is preferentially located on the basolateral surface of the transporting epithelial cells so that a simple correlation  of structure and function in terms of the Koefoed-Johnsen and Ussing hypothesis does not seem possible. With little dispute that this enzyme is, nonetheless, the probable site for conversion of metabolic energy to transport-related work, we summarized as well the more macroscopic structural characteristics of epithelia which serve to typify each of the four classes in terms of the direction and tonicity of transported fluid. The apparently systematic differences in cell shape and cell-cell junctions that are summarized here may well be an important consideration for the development of a useful holistic theory with which to explain the transepithelial transport of salt and water.", "contents": "Distribution of Na+-pump sites in transporting epithelia. There are three techniques for the localization of intraepithelial Na+, K+-ATPase (usually equated with the Na+-pump) that offer reasonable specificity and resolution: the nitrophenylphosphatase assay of Ernst, the immunoferritin procedure of Kyte, and the radioautographic localization of tritiated ouabain as developed by Stirling. These have now been applied to a wide range of epithelia covering the four classes of interest here: isotonic and hypertonic absorbers and isotonic and hypertonic secretors. A review of published results reveals that in every case (except for the choroid plexus) the enzyme is preferentially located on the basolateral surface of the transporting epithelial cells so that a simple correlation  of structure and function in terms of the Koefoed-Johnsen and Ussing hypothesis does not seem possible. With little dispute that this enzyme is, nonetheless, the probable site for conversion of metabolic energy to transport-related work, we summarized as well the more macroscopic structural characteristics of epithelia which serve to typify each of the four classes in terms of the direction and tonicity of transported fluid. The apparently systematic differences in cell shape and cell-cell junctions that are summarized here may well be an important consideration for the development of a useful holistic theory with which to explain the transepithelial transport of salt and water."}
{"id": "PMID:216594", "title": "Hormonal regulation of cAMP-independent protein phosphokinase activities: thyroxine and cortisol control of enzymes from rat liver cytosol.", "content": "Thyroxine control of cAMP-independent histone and casein phosphokinase activities was studied in thyroidectomized rats treated with thyroxine. All activities were evaluated in the presence of a thermostable inhibitor of cAMP-dependent enzymes. Cytosol enzymes can be resolved by sucrose gradient ultracentrifugation into three peaks of histone kinase activity (3.2S, 5S and 7.2S) and two peaks of casein kinases (3.6S and 7.1S). Neither thyroidectomy nor subsequent treatment of operated animals with thyroxine modifies the total histone kinase activity estimated, either in total cytosol or after its fractionation by the sucrose gradient ultracentrifugation. The activity ratios of different peaks were, however, changed. Casein kinase activity was significantly decreased after thyroidectomy (about 50%). Subsequent treatment with thyroxine restored this activity to its initial value. Sucrose gradient ultracentrifugation analysis showed that thyroxine action on the casein kinase activity is very specific. Only molecules that sediment in the 9S region were significantly stimulated by the hormone. Cortisol action on the casein kinase activity was studied in adrenalectomized animals treated with hormone for 24 h. Cortisol decreases the total casein kinase activity by about 30%. Sucrose gradient ultracentrifugation analysis showed that the population of molecules sedimenting at about 9S was the most sensitive to cortisol. The above data show that both thyroxine and cortisol control, in a selective way, the activities of cAMP-independent protein kinases. The same kinase molecules can be under double control by two different hormones that have opposite effects.", "contents": "Hormonal regulation of cAMP-independent protein phosphokinase activities: thyroxine and cortisol control of enzymes from rat liver cytosol. Thyroxine control of cAMP-independent histone and casein phosphokinase activities was studied in thyroidectomized rats treated with thyroxine. All activities were evaluated in the presence of a thermostable inhibitor of cAMP-dependent enzymes. Cytosol enzymes can be resolved by sucrose gradient ultracentrifugation into three peaks of histone kinase activity (3.2S, 5S and 7.2S) and two peaks of casein kinases (3.6S and 7.1S). Neither thyroidectomy nor subsequent treatment of operated animals with thyroxine modifies the total histone kinase activity estimated, either in total cytosol or after its fractionation by the sucrose gradient ultracentrifugation. The activity ratios of different peaks were, however, changed. Casein kinase activity was significantly decreased after thyroidectomy (about 50%). Subsequent treatment with thyroxine restored this activity to its initial value. Sucrose gradient ultracentrifugation analysis showed that thyroxine action on the casein kinase activity is very specific. Only molecules that sediment in the 9S region were significantly stimulated by the hormone. Cortisol action on the casein kinase activity was studied in adrenalectomized animals treated with hormone for 24 h. Cortisol decreases the total casein kinase activity by about 30%. Sucrose gradient ultracentrifugation analysis showed that the population of molecules sedimenting at about 9S was the most sensitive to cortisol. The above data show that both thyroxine and cortisol control, in a selective way, the activities of cAMP-independent protein kinases. The same kinase molecules can be under double control by two different hormones that have opposite effects."}
{"id": "PMID:216595", "title": "Prolactin receptor on dissociated mammary epithelial cells at different stages of development.", "content": "Properties of prolactin receptors were measured by monitoring [125I]prolactin binding to specific receptor sites on collagenase-dissociated mammary epithelial cells of virgin, pregnant and lactating mice. On a Scatchard plot the data generated a straight line and the estimated dissociation constant (Kd) and number of receptor sites on lactating cells were 0.9 x 10(-9) and 1540 per cell. The [125I]prolactin binding was inhibited in presence of unlabeled prolactin and other lactogenic polypeptide hormones, but not by nonlactogenic polypeptide hormones. The [125I]prolactin binding was sensitive to pronase and trypsin but not to DNAase, RNAase and hyaluronidase. Scatchard plot analysis further showed that while the number of receptors on mammary cells was variable at different stages of endocrine regulated developmental changes of the gland, Kd of the hormone--receptor complex generally remained similar. The high level of prolactin receptors on mammary cells of virgins was reduced during pregnancy and the lactating mammary cells showed a highly elevated level of prolactin receptors. The results demonstrate that specific prolactin receptors can be measured on collagenase dissociated mammary epithelial cells and this method permits a direct assessment of the number of receptors on a per cell basis rather than indirect estimates, based on average DNA or protein content of the tissue, composed of heterogeneous cell types.", "contents": "Prolactin receptor on dissociated mammary epithelial cells at different stages of development. Properties of prolactin receptors were measured by monitoring [125I]prolactin binding to specific receptor sites on collagenase-dissociated mammary epithelial cells of virgin, pregnant and lactating mice. On a Scatchard plot the data generated a straight line and the estimated dissociation constant (Kd) and number of receptor sites on lactating cells were 0.9 x 10(-9) and 1540 per cell. The [125I]prolactin binding was inhibited in presence of unlabeled prolactin and other lactogenic polypeptide hormones, but not by nonlactogenic polypeptide hormones. The [125I]prolactin binding was sensitive to pronase and trypsin but not to DNAase, RNAase and hyaluronidase. Scatchard plot analysis further showed that while the number of receptors on mammary cells was variable at different stages of endocrine regulated developmental changes of the gland, Kd of the hormone--receptor complex generally remained similar. The high level of prolactin receptors on mammary cells of virgins was reduced during pregnancy and the lactating mammary cells showed a highly elevated level of prolactin receptors. The results demonstrate that specific prolactin receptors can be measured on collagenase dissociated mammary epithelial cells and this method permits a direct assessment of the number of receptors on a per cell basis rather than indirect estimates, based on average DNA or protein content of the tissue, composed of heterogeneous cell types."}
{"id": "PMID:216596", "title": "Pregnenolone biosynthesis in isolated cells of Snell rat adrenocortical carcinoma 494.", "content": "Adrenocorticotrophin (ACTH) produced an insignificant stimulation of pregnenolone biosynthesis from endogenous precursors in isolated cells prepared from the rat Snell adrenal carcinoma 494. On the addition of 25-hydroxycholesterol, the rate of pregnenolone synthesis increased 10-fold. These results, noting also the very low cholesterol content of the tumor cells, suggested that lack of cholesterol was responsible for the poor steroidogenic response of the cells to ACTH. Endogenous pregnenolone production was sensitive to cytochalasin B as well as cycloheximide. However, pregnenolone synthesis after the addition of 25-hydroxycholesterol was not affected by these inhibitors. Removal of cycloheximide from the cells resulted in the immediate restoration of the initial rate of pregnenolone synthesis from endogenous precursors. This suggested that cycloheximide was interfering with the action of a stable activated intracellular messenger.", "contents": "Pregnenolone biosynthesis in isolated cells of Snell rat adrenocortical carcinoma 494. Adrenocorticotrophin (ACTH) produced an insignificant stimulation of pregnenolone biosynthesis from endogenous precursors in isolated cells prepared from the rat Snell adrenal carcinoma 494. On the addition of 25-hydroxycholesterol, the rate of pregnenolone synthesis increased 10-fold. These results, noting also the very low cholesterol content of the tumor cells, suggested that lack of cholesterol was responsible for the poor steroidogenic response of the cells to ACTH. Endogenous pregnenolone production was sensitive to cytochalasin B as well as cycloheximide. However, pregnenolone synthesis after the addition of 25-hydroxycholesterol was not affected by these inhibitors. Removal of cycloheximide from the cells resulted in the immediate restoration of the initial rate of pregnenolone synthesis from endogenous precursors. This suggested that cycloheximide was interfering with the action of a stable activated intracellular messenger."}
{"id": "PMID:216598", "title": "Virus-induced diabetes in mice: a quantitative evaluation of islet cell population by immunofluorescence technique.", "content": "The endocrine cell populations of pancreatic islets in encephalomyocarditis (EMC)-virus infected mice were assessed quanititatively by immunofluorescence using specific antisera against 4 islet hormones. A marked reduction of the volume of insulin-containing (B-) cells (up to one tenth of control values) was observed at all stages studied in the hyperglycaemic mice. This was accompanied by the inversion of the normal ratio between B- and non B-cells. The volume of the latter cell types was also modified at different time points after infection: glucagon-cells were augmented 14 days after infection; PP-cells were decreased 2--3 days and 21 days after infection; somatostatin-cells decreased to one-fourth of control values in hyperglycaemic animals 21 days after infection. The latter results suggest that non B-cells are also involved in islet reaction to virus infection.", "contents": "Virus-induced diabetes in mice: a quantitative evaluation of islet cell population by immunofluorescence technique. The endocrine cell populations of pancreatic islets in encephalomyocarditis (EMC)-virus infected mice were assessed quanititatively by immunofluorescence using specific antisera against 4 islet hormones. A marked reduction of the volume of insulin-containing (B-) cells (up to one tenth of control values) was observed at all stages studied in the hyperglycaemic mice. This was accompanied by the inversion of the normal ratio between B- and non B-cells. The volume of the latter cell types was also modified at different time points after infection: glucagon-cells were augmented 14 days after infection; PP-cells were decreased 2--3 days and 21 days after infection; somatostatin-cells decreased to one-fourth of control values in hyperglycaemic animals 21 days after infection. The latter results suggest that non B-cells are also involved in islet reaction to virus infection."}
{"id": "PMID:216599", "title": "Acid glycohydrolase in Chinese hamster with spontaneous diabetes. IV. Diabetes- and line-dependent variation in plasma enzyme activity.", "content": "The activity of five glycohydrolases was measured in the plasma of Chinese hamsters from eight highly inbred lines in the Upjohn colony. The diabetic animals showed elevated activities of plasma beta-D-galactosidase, N-acetyl-beta-D-glucosaminidase and N-acetyl-beta-D-galactosaminidase but similar activities of plasma alpha-D-glucosidase and alpha-D-galactosidase to the nondiabetic animals. Line-specific variation was observed in all five enzymes and anomalies were especially evident in N-acetyl-beta-D-glucosaminidase and N-acetyl-beta-D-galactosaminidase activity. In two diabetic lines, AC and Z, activities of these two enzymes were not elevated although significant correlation was found with blood sugar levels. The pronounced difference in the plasma activity of N-acetyl-beta-D-glucosaminidase in two diabetic lines, XA and AC, did not involve plasma inhibitors or activators, as evidenced by the coincidence in observed and calculated activities in mixed plasma samples, or specific isozymes, concluded from the similar elution profiles on ion-exchange column and thermostability curves. These data suggest that diabetes-related changes in plasma glycohydrolase activities are dictated by genetic factors and may be involved in the development of complications.", "contents": "Acid glycohydrolase in Chinese hamster with spontaneous diabetes. IV. Diabetes- and line-dependent variation in plasma enzyme activity. The activity of five glycohydrolases was measured in the plasma of Chinese hamsters from eight highly inbred lines in the Upjohn colony. The diabetic animals showed elevated activities of plasma beta-D-galactosidase, N-acetyl-beta-D-glucosaminidase and N-acetyl-beta-D-galactosaminidase but similar activities of plasma alpha-D-glucosidase and alpha-D-galactosidase to the nondiabetic animals. Line-specific variation was observed in all five enzymes and anomalies were especially evident in N-acetyl-beta-D-glucosaminidase and N-acetyl-beta-D-galactosaminidase activity. In two diabetic lines, AC and Z, activities of these two enzymes were not elevated although significant correlation was found with blood sugar levels. The pronounced difference in the plasma activity of N-acetyl-beta-D-glucosaminidase in two diabetic lines, XA and AC, did not involve plasma inhibitors or activators, as evidenced by the coincidence in observed and calculated activities in mixed plasma samples, or specific isozymes, concluded from the similar elution profiles on ion-exchange column and thermostability curves. These data suggest that diabetes-related changes in plasma glycohydrolase activities are dictated by genetic factors and may be involved in the development of complications."}
{"id": "PMID:216600", "title": "The metabolism of cyclic AMP and glucose in isolated islets from Acomys cahirinus.", "content": "Glucose-induced cyclic (3H) AMP accumulation, insulin secretory responses and the metabolism of glucose were studied in pancreatic islets from Acomys cahirinus. 27.7 mmol/l of glucose stimulated neither islet cyclic (3H) AMP accumulation nor insulin release during the first 5 min of incubation. Stimulation by glucose of cyclic (3H) AMP was observed after 15 min of incubation and insulin release was markedly stimulated between 15 and 30 min. The utilization of glucose, measured as the production of (3H)2O from (5--3H) glucose was stimulated by glucose after 10 min and proceeded at an apparently linear rate during a 20 min incubation period. In incubations of 5 min, glibenclamide, glucagon or chloromercuribenzene-p-sulphonic acid failed to stimulate islet cyclic (3H) AMP accumulation. 3-isobutyl-l-methylxanthine in a concentration of 1.0 mmol/l was the only agent tested that elevated rapidly (1 min) islet cyclic (3H) AMP. None of the agents tested elicited an insulin secretory response in 5 min incubations. It is concluded that 1) no gross defect is apparent in the utilization of glucose by Acomys islets, 2) the secretory derangement of the Acomys is associated with a delayed cyclic AMP response to glucose, 3) however a decreased level of cyclic AMP cannot be the sole explanation for the delayed insulin secretion in the Acomys.", "contents": "The metabolism of cyclic AMP and glucose in isolated islets from Acomys cahirinus. Glucose-induced cyclic (3H) AMP accumulation, insulin secretory responses and the metabolism of glucose were studied in pancreatic islets from Acomys cahirinus. 27.7 mmol/l of glucose stimulated neither islet cyclic (3H) AMP accumulation nor insulin release during the first 5 min of incubation. Stimulation by glucose of cyclic (3H) AMP was observed after 15 min of incubation and insulin release was markedly stimulated between 15 and 30 min. The utilization of glucose, measured as the production of (3H)2O from (5--3H) glucose was stimulated by glucose after 10 min and proceeded at an apparently linear rate during a 20 min incubation period. In incubations of 5 min, glibenclamide, glucagon or chloromercuribenzene-p-sulphonic acid failed to stimulate islet cyclic (3H) AMP accumulation. 3-isobutyl-l-methylxanthine in a concentration of 1.0 mmol/l was the only agent tested that elevated rapidly (1 min) islet cyclic (3H) AMP. None of the agents tested elicited an insulin secretory response in 5 min incubations. It is concluded that 1) no gross defect is apparent in the utilization of glucose by Acomys islets, 2) the secretory derangement of the Acomys is associated with a delayed cyclic AMP response to glucose, 3) however a decreased level of cyclic AMP cannot be the sole explanation for the delayed insulin secretion in the Acomys."}
{"id": "PMID:216604", "title": "[Carcinoma of the apocrine glands of the vulva with intraepidermal spreading under the picture of invasive Paget's disease (author's transl)].", "content": "The histological findings of Paget's disease of the nipple and of extramammary localisation are well known. The relationship to the so called \"adnexal carcinoma\" has not become clear to this moment. We report a case of combination of invasive vulva Paget's disease and adnexal carcinoma of the apocrine vulvar glands. Our findings are discussed with the statements of literature about aetiology and pathogenes.", "contents": "[Carcinoma of the apocrine glands of the vulva with intraepidermal spreading under the picture of invasive Paget's disease (author's transl)]. The histological findings of Paget's disease of the nipple and of extramammary localisation are well known. The relationship to the so called \"adnexal carcinoma\" has not become clear to this moment. We report a case of combination of invasive vulva Paget's disease and adnexal carcinoma of the apocrine vulvar glands. Our findings are discussed with the statements of literature about aetiology and pathogenes."}
{"id": "PMID:216611", "title": "Multiple fibrous xanthomas of tendon sheath.", "content": "Fibrous xanthomas of the digital tendon sheath system are a common benign tumour. The varying recurrence rates cited in the literature have usually been attributed to inadequate surgical excision. However, Boyes (1964) has suggested \"seeding\" as a possible mechanism to explain persistence of the tumour. Our case of multiple fibrous xanthomas at different levels in a single digital sheath system is presented as an example of \"seeding\" along the tendon sheath.", "contents": "Multiple fibrous xanthomas of tendon sheath. Fibrous xanthomas of the digital tendon sheath system are a common benign tumour. The varying recurrence rates cited in the literature have usually been attributed to inadequate surgical excision. However, Boyes (1964) has suggested \"seeding\" as a possible mechanism to explain persistence of the tumour. Our case of multiple fibrous xanthomas at different levels in a single digital sheath system is presented as an example of \"seeding\" along the tendon sheath."}
{"id": "PMID:216612", "title": "[Obesity and adipose tissue. 2. Hormonal regulation of adipose tissue metabolism].", "content": "The effects of hormones on human adipose tissue are reviewed with respect to the pathogenesis, prevention and therapy of obesity. Insulin. The insulin-resistance in the obese is associated with a decrease of the number of insulin receptor sites, which is likely to be secondary to increased insulin levels. Catecholamines. Human adipose tissue contains alpha- and beta-adrenergic receptors. Alterations in the relation of alpha- and beta-adrenergic responsiveness may be important in the pathogenesis of regional forms of obesity. Gastrointestinal hormones. As opposed to adipose tissue of other species lipolytic effects of gastrointestinal hormones were as yet not clearly demonstrated in human fat cells. Prostaglandins were implicated in the pathogenesis of metabolic obesity. However, the effects of these C-20 fatty acids on human adipose tissue remain to be elucidated. Parathyroid hormone has been shown to possess lipolytic activity in vitro. This property may be important under physiological conditions too. Triglyceride storage diseases and lipomatoses are discussed as models for studying impaired hormonal responsiveness in human adipose tissue.", "contents": "[Obesity and adipose tissue. 2. Hormonal regulation of adipose tissue metabolism]. The effects of hormones on human adipose tissue are reviewed with respect to the pathogenesis, prevention and therapy of obesity. Insulin. The insulin-resistance in the obese is associated with a decrease of the number of insulin receptor sites, which is likely to be secondary to increased insulin levels. Catecholamines. Human adipose tissue contains alpha- and beta-adrenergic receptors. Alterations in the relation of alpha- and beta-adrenergic responsiveness may be important in the pathogenesis of regional forms of obesity. Gastrointestinal hormones. As opposed to adipose tissue of other species lipolytic effects of gastrointestinal hormones were as yet not clearly demonstrated in human fat cells. Prostaglandins were implicated in the pathogenesis of metabolic obesity. However, the effects of these C-20 fatty acids on human adipose tissue remain to be elucidated. Parathyroid hormone has been shown to possess lipolytic activity in vitro. This property may be important under physiological conditions too. Triglyceride storage diseases and lipomatoses are discussed as models for studying impaired hormonal responsiveness in human adipose tissue."}
{"id": "PMID:216614", "title": "Photolabile and paramagnetic derivatives of the nucleoside X and of Escherichia coli tRNAPhe.", "content": "The synthesis of N3-[3-L-(5-azido-2-nitrobenzamido)-3-carboxypropyl]uridine (4b) and N3-[3-carboxy-3-L-(2,2,5,5-tetramethyl-3-pyrroline-3-carbonylamino)propyl]uridine Npyr-oxyl (4c) starting from the nucleoside X (4a) and the appropriate N-hydroxysuccinimide ester 1 or 2 is described. After acylation of tRNAPhe from E. coli (5a) with 1 or 2, the photolabile tRNAPhe derivative 5b and the paramagnetic tRNAPhe derivative 5c could be isolated. The position of modification in the polynucleotide chain was elucidated by comparison of the ribonuclease II/alkaline phosphatase digestion products of the substituted and unsubstituted tRNAPhe samples, and was identified as being exclusively the amino group of the nucleoside X in position 47 of E. coli tRNAPhe.", "contents": "Photolabile and paramagnetic derivatives of the nucleoside X and of Escherichia coli tRNAPhe. The synthesis of N3-[3-L-(5-azido-2-nitrobenzamido)-3-carboxypropyl]uridine (4b) and N3-[3-carboxy-3-L-(2,2,5,5-tetramethyl-3-pyrroline-3-carbonylamino)propyl]uridine Npyr-oxyl (4c) starting from the nucleoside X (4a) and the appropriate N-hydroxysuccinimide ester 1 or 2 is described. After acylation of tRNAPhe from E. coli (5a) with 1 or 2, the photolabile tRNAPhe derivative 5b and the paramagnetic tRNAPhe derivative 5c could be isolated. The position of modification in the polynucleotide chain was elucidated by comparison of the ribonuclease II/alkaline phosphatase digestion products of the substituted and unsubstituted tRNAPhe samples, and was identified as being exclusively the amino group of the nucleoside X in position 47 of E. coli tRNAPhe."}
{"id": "PMID:216615", "title": "beta-Nicotinamide-alpha-adenine dinucleotide. Synthesis and properties of a coenzyme analog.", "content": "It was not possible to synthesize beta-nicotinamide-alpha-adenine dinucleotide (NalphaAD) via the NAD pyrophosphorylase-catalyzed reaction of beta-nicotinamide mononucleotide and alpha-adenosine-5'-O-triphosphate. It was therefore prepared by reacting a mixture of beta-nicotinamide mononucleotide and alpha-adenosine-5'-O-monophosphate in aqueous pyridine, using N,N'-dicyclohexylcarbodiimide as condensing agent. NalphaAD can replace NAD in the lactate-dehydrogenase-catalyzed oxidation of lactate to pyruvate with LDH 4M from hog muscle as well as LDH 4H from pig heart. Km values are found to be about one order of magnitude higher for NalphaAD than for NAD. The turnover number for NalphaAD with LDH 4H is similar to that of NAD (95%), whereas it is reduced to one third (35%) in the reaction with LDH 4M. Experiments findings are discussed on the lines of a NAD-equivalent conformation of NalphaAD in the holoenzyme complex.", "contents": "beta-Nicotinamide-alpha-adenine dinucleotide. Synthesis and properties of a coenzyme analog. It was not possible to synthesize beta-nicotinamide-alpha-adenine dinucleotide (NalphaAD) via the NAD pyrophosphorylase-catalyzed reaction of beta-nicotinamide mononucleotide and alpha-adenosine-5'-O-triphosphate. It was therefore prepared by reacting a mixture of beta-nicotinamide mononucleotide and alpha-adenosine-5'-O-monophosphate in aqueous pyridine, using N,N'-dicyclohexylcarbodiimide as condensing agent. NalphaAD can replace NAD in the lactate-dehydrogenase-catalyzed oxidation of lactate to pyruvate with LDH 4M from hog muscle as well as LDH 4H from pig heart. Km values are found to be about one order of magnitude higher for NalphaAD than for NAD. The turnover number for NalphaAD with LDH 4H is similar to that of NAD (95%), whereas it is reduced to one third (35%) in the reaction with LDH 4M. Experiments findings are discussed on the lines of a NAD-equivalent conformation of NalphaAD in the holoenzyme complex."}
{"id": "PMID:216616", "title": "Lipid-protein interaction in reconstituted cytochrome c oxidase/phospholipid membranes.", "content": "Deuterium and 31P nuclear magnetic resonance have been employed in an investigation of the effect of cytochrome c oxidase (EC 1.9.3.1) on the structure of lecithin bilayers. Cytochrome c oxidase was isolated from beef heart mitochondria in lipid-free form and reconstituted as a functional enzyme in bilayers composed of synthetic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine. Two separate reconstitution experiments were performed in which the lipid was selectively deuterated either at the C-5' or at the C-14' segment of the palmitic acyl chain. The phospholipid-to-protein ratio of both reconstituted complexes was 0.74 (mg/mg), corresponding to about 200 molecules lipid per molecule cytochrome c oxidase. The deuterium quadrupole splitting deltanuQ, and the phosphorus chemical shielding anisotropy, deltasigma, of the cytochrome c oxidase-phospholipid recombinants were measured as a function of temperature and compared to the results obtained for the pure lipid membrane without protein for the pure lipid membrane without protein. deltanuQ and deltasigma are highly sensitive to the structural organization of the lipid membrane and these measurements demonstrate that the incorporation of cytochrome c oxidase into phosphatidylcholine bilayers leads to a more disordered conformational state of the lipids. This result can be explained by a rapid exchange between lipids in direct contact with hydrophobic protein and those further away from it (exchange rate greater than 10(4) Hz). The irregular protein surface is sensed by all lipid molecules and induces a more disordered bilayer structure. In contrast to previous interpretations, our measurements do not suggest a special type of boundary lipid.", "contents": "Lipid-protein interaction in reconstituted cytochrome c oxidase/phospholipid membranes. Deuterium and 31P nuclear magnetic resonance have been employed in an investigation of the effect of cytochrome c oxidase (EC 1.9.3.1) on the structure of lecithin bilayers. Cytochrome c oxidase was isolated from beef heart mitochondria in lipid-free form and reconstituted as a functional enzyme in bilayers composed of synthetic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine. Two separate reconstitution experiments were performed in which the lipid was selectively deuterated either at the C-5' or at the C-14' segment of the palmitic acyl chain. The phospholipid-to-protein ratio of both reconstituted complexes was 0.74 (mg/mg), corresponding to about 200 molecules lipid per molecule cytochrome c oxidase. The deuterium quadrupole splitting deltanuQ, and the phosphorus chemical shielding anisotropy, deltasigma, of the cytochrome c oxidase-phospholipid recombinants were measured as a function of temperature and compared to the results obtained for the pure lipid membrane without protein for the pure lipid membrane without protein. deltanuQ and deltasigma are highly sensitive to the structural organization of the lipid membrane and these measurements demonstrate that the incorporation of cytochrome c oxidase into phosphatidylcholine bilayers leads to a more disordered conformational state of the lipids. This result can be explained by a rapid exchange between lipids in direct contact with hydrophobic protein and those further away from it (exchange rate greater than 10(4) Hz). The irregular protein surface is sensed by all lipid molecules and induces a more disordered bilayer structure. In contrast to previous interpretations, our measurements do not suggest a special type of boundary lipid."}
{"id": "PMID:216617", "title": "On the modification of adenosine kinase by thiols.", "content": "The catalytic activity of adenosine kinase (EC 2.7.1.20) from yeast is very labile. Even incubation with thiols provokes a loss of two thirds of its enzymatic activity. Concomitantly, two SH-groups appear on the enzyme in addition to the single SH-group already present in the untreated enzyme, the latter being absolutely essential for activity. Treatment of adenosine kinase with thiols does not substantially affect the binding of the substrates adenosine and ATP-Mg2. The reactivity of the two newly formed SH-groups is diminished in the presence of ATP-Mg2, whereas adenosine has no influence. The opposite holds for the reactivity of the single SH-group essential for enzymatic activity. Complete reactivation of the enzymatic activity after incubation of adenosine kinase with thiols can be achieved by reoxidation of the enzyme in presence of high concentrations of adenosine. These observations suggest the notion that adenosine kinase contains an essential SH-group close to the adenosine-binding site and a disulfide bridge near to the binding site of ATP-Mg2, the latter being easily accesible to the reduction by thiols.", "contents": "On the modification of adenosine kinase by thiols. The catalytic activity of adenosine kinase (EC 2.7.1.20) from yeast is very labile. Even incubation with thiols provokes a loss of two thirds of its enzymatic activity. Concomitantly, two SH-groups appear on the enzyme in addition to the single SH-group already present in the untreated enzyme, the latter being absolutely essential for activity. Treatment of adenosine kinase with thiols does not substantially affect the binding of the substrates adenosine and ATP-Mg2. The reactivity of the two newly formed SH-groups is diminished in the presence of ATP-Mg2, whereas adenosine has no influence. The opposite holds for the reactivity of the single SH-group essential for enzymatic activity. Complete reactivation of the enzymatic activity after incubation of adenosine kinase with thiols can be achieved by reoxidation of the enzyme in presence of high concentrations of adenosine. These observations suggest the notion that adenosine kinase contains an essential SH-group close to the adenosine-binding site and a disulfide bridge near to the binding site of ATP-Mg2, the latter being easily accesible to the reduction by thiols."}
{"id": "PMID:216618", "title": "[Synthesis of [Trp(1-But)9]- and [Trp(2,5,7-But3)9] corticotropin-(1--19)-nonadecapeptideamide (author's transl)].", "content": "The title analogues of corticoptropin-(1--19)-nonadecapeptidamide in which the tryptophan residue in position 9 has been replaced by tert-butylated tryptophan derivatives, were prepared according to the methods of conventional peptide synthesis in solution. Both analogues showed remarkable steroidogenic activity as measured by Sayers test. The unexpectedly high biological potency is discussed.", "contents": "[Synthesis of [Trp(1-But)9]- and [Trp(2,5,7-But3)9] corticotropin-(1--19)-nonadecapeptideamide (author's transl)]. The title analogues of corticoptropin-(1--19)-nonadecapeptidamide in which the tryptophan residue in position 9 has been replaced by tert-butylated tryptophan derivatives, were prepared according to the methods of conventional peptide synthesis in solution. Both analogues showed remarkable steroidogenic activity as measured by Sayers test. The unexpectedly high biological potency is discussed."}
{"id": "PMID:216620", "title": "[Enzymatic digestibility of peptides containing tert-butyltryptophan residues (author's transl)].", "content": "The effects of tert-butylation of tryptophan residues in peptide chains on the enzymatic digestibility were investigated. It was shown that replacement of tryptophan in position 9 of Corticotropin-(1--19)-nonadecapeptidamide by a mono- or tri-tert-butylated tryptophan enhances the resistance of the resulting analogue against proteolytic enzymes.", "contents": "[Enzymatic digestibility of peptides containing tert-butyltryptophan residues (author's transl)]. The effects of tert-butylation of tryptophan residues in peptide chains on the enzymatic digestibility were investigated. It was shown that replacement of tryptophan in position 9 of Corticotropin-(1--19)-nonadecapeptidamide by a mono- or tri-tert-butylated tryptophan enhances the resistance of the resulting analogue against proteolytic enzymes."}
{"id": "PMID:216625", "title": "Confirmation of regional assignment of nucleoside phosphorylase (NP) on chromosome 14 by gene dosage studies.", "content": "Gene dosage studies yielded results consistent with assignment of the locus for nucleoside phosphorylase to band 14q13. The red blood cells from a patient with the karyotype 47,XX,+der(14),t(8;14)(8qter leads to 8q24::14q21 leads to 14pter)pat had enzyme activity 50% higher than red cells from 47 normal controls, two trisomies involving chromosomes other than 14, and five balanced translocations involving chromosome 14. On the other hand, the red cells of a case with a karyotype 45,XX,-14,-22+der(22),t(14;22)(14qter leads to 14q11 or 14q12::22p11 leads to 22qter)mat and a case with a a karyotype 47,XX,+der(14),t(14;16)(14pter leads to 14q11::16q24 leads to 16qter)mat had normal activity", "contents": "Confirmation of regional assignment of nucleoside phosphorylase (NP) on chromosome 14 by gene dosage studies. Gene dosage studies yielded results consistent with assignment of the locus for nucleoside phosphorylase to band 14q13. The red blood cells from a patient with the karyotype 47,XX,+der(14),t(8;14)(8qter leads to 8q24::14q21 leads to 14pter)pat had enzyme activity 50% higher than red cells from 47 normal controls, two trisomies involving chromosomes other than 14, and five balanced translocations involving chromosome 14. On the other hand, the red cells of a case with a karyotype 45,XX,-14,-22+der(22),t(14;22)(14qter leads to 14q11 or 14q12::22p11 leads to 22qter)mat and a case with a a karyotype 47,XX,+der(14),t(14;16)(14pter leads to 14q11::16q24 leads to 16qter)mat had normal activity"}
{"id": "PMID:216626", "title": "Appearance of hCG-receptor after conversion of newborn ovarian cells into testicular structures by H-Y antigen in vitro.", "content": "In a previous report (Zenzes et al., 1978b) it was shown that dissociated ovarian cells of newborn rats in vitro, if exposed to H-Y antigen, reorganize into testicular structures. The current study was designed to see whether this morphological conversion also results in a functional conversion. The LH/hCG receptor was used as a parameter characteristic for the newborn testis, but not for the newborn ovary. In the converted ovary, the LH/hCG receptor becomes detectable a few hours after onset of the culture and remains continuously present afterward. The appearance of this receptor may be due to a hormone-like action of H-Y antigen.", "contents": "Appearance of hCG-receptor after conversion of newborn ovarian cells into testicular structures by H-Y antigen in vitro. In a previous report (Zenzes et al., 1978b) it was shown that dissociated ovarian cells of newborn rats in vitro, if exposed to H-Y antigen, reorganize into testicular structures. The current study was designed to see whether this morphological conversion also results in a functional conversion. The LH/hCG receptor was used as a parameter characteristic for the newborn testis, but not for the newborn ovary. In the converted ovary, the LH/hCG receptor becomes detectable a few hours after onset of the culture and remains continuously present afterward. The appearance of this receptor may be due to a hormone-like action of H-Y antigen."}
{"id": "PMID:216627", "title": "A genetic study of two French Guiana Amerindian populations. II. Rare electrophoretic variants.", "content": "Two Amerindian populations of French Guiana were investigated for plasma proteins and red-cell enzymes. In the Wayampi tribe, rare variants were identified in 4 systems. The corresponding alleles are designated AK1 3 Wayampi, PGM1 (4/10) Wayampi, PGM2 6 Wayampi, and TfD. In the Emerillon tribe, a variant allele of PGM2, designated PGM2 6 Emerillon, was identified. For three of the systems, PGM1, PGM2, Tf, similar isozymes have been described in other Amerindian populations. These findings suggest that the corresponding alleles may have the same origin.", "contents": "A genetic study of two French Guiana Amerindian populations. II. Rare electrophoretic variants. Two Amerindian populations of French Guiana were investigated for plasma proteins and red-cell enzymes. In the Wayampi tribe, rare variants were identified in 4 systems. The corresponding alleles are designated AK1 3 Wayampi, PGM1 (4/10) Wayampi, PGM2 6 Wayampi, and TfD. In the Emerillon tribe, a variant allele of PGM2, designated PGM2 6 Emerillon, was identified. For three of the systems, PGM1, PGM2, Tf, similar isozymes have been described in other Amerindian populations. These findings suggest that the corresponding alleles may have the same origin."}
{"id": "PMID:216628", "title": "Properties of morphologically variant haploid frog cells formed by combined treatment with Mengo virus and the polyene antibiotic mediocidin.", "content": "Comparisons have been made of cell surface glycoproteins, concanavalin A agglutinability, and cloning efficiencies in liquid media of ICR 2A (haploid frog cells), ICR 2A M (three cloned populations of haploid frog cells resistant to 5 microgram per ml of the polyene antibiotic mediocidin), and ICR 2A M/MV cells (five cloned populations of morphologically variant haploid frog cells produced by exposure of the parental cells to the combined effects of mediocidin and an RNA mammalian virus, Mengo virus). Independently isolated ICR 2A M/MV clones exhibited altered cell surface glycoproteins, increased concanavalin A agglutinability, and enhanced cloning efficiency in liquid media when compared with ICR 2A parental cells. In contrast, ICR 2A M cells had properties similar to ICR 2A cells, with the exception of the former's increased resistance to mediocidin. The differences in properties between ICR 2A M/MV and ICR 2A cells suggest that alterations resembling transformation have occurred in ICR 2A M/MV cells as a consequence of combined treatment with mediocidin and Mengo virus.", "contents": "Properties of morphologically variant haploid frog cells formed by combined treatment with Mengo virus and the polyene antibiotic mediocidin. Comparisons have been made of cell surface glycoproteins, concanavalin A agglutinability, and cloning efficiencies in liquid media of ICR 2A (haploid frog cells), ICR 2A M (three cloned populations of haploid frog cells resistant to 5 microgram per ml of the polyene antibiotic mediocidin), and ICR 2A M/MV cells (five cloned populations of morphologically variant haploid frog cells produced by exposure of the parental cells to the combined effects of mediocidin and an RNA mammalian virus, Mengo virus). Independently isolated ICR 2A M/MV clones exhibited altered cell surface glycoproteins, increased concanavalin A agglutinability, and enhanced cloning efficiency in liquid media when compared with ICR 2A parental cells. In contrast, ICR 2A M cells had properties similar to ICR 2A cells, with the exception of the former's increased resistance to mediocidin. The differences in properties between ICR 2A M/MV and ICR 2A cells suggest that alterations resembling transformation have occurred in ICR 2A M/MV cells as a consequence of combined treatment with mediocidin and Mengo virus."}
{"id": "PMID:216633", "title": "Rapid micromeasurement of neutrophil exocytosis.", "content": "A simple method is described for the visual detection of neutrophil granule exocytosis. The microassay measures release of myeloperoxidase from azurophilic granules following neutrophil stimulation and can be accomplished in less than 30 min. The assay is sensitive, reproducible from day to day, and does not require separation of leukocytes from the reaction before enzyme assay. The procedure is also applicable to the rapid measurement of the suppression of degranulation by antiinflammatory agents.", "contents": "Rapid micromeasurement of neutrophil exocytosis. A simple method is described for the visual detection of neutrophil granule exocytosis. The microassay measures release of myeloperoxidase from azurophilic granules following neutrophil stimulation and can be accomplished in less than 30 min. The assay is sensitive, reproducible from day to day, and does not require separation of leukocytes from the reaction before enzyme assay. The procedure is also applicable to the rapid measurement of the suppression of degranulation by antiinflammatory agents."}
{"id": "PMID:216634", "title": "Breakdown of articular cartilage proteoglycans by lymphokine-activated macrophages.", "content": "Lymphokine supernatants (LE) prepared from antigen sensitive lymphocytes caused an inhibition of migration of macrophages from capillary tubes. Control supernatants (LC) had no effect. The lymphokine supernatants, when added to macrophage cultures (the equivalent of 60 x 10(6) lymphocytes added to 40 x 10(6) macrophages), activated the macrophages so that they secreted the enzyme collagenase after 48 h and 72 h of culture. No collagenase was detected before 48 h or from macrophage supernatants to which LC was added. The macrophage supernatants (LE but not LC) also contained factors (probably enzymes) that, when added to a piece of articular cartilage in medium, caused a partial loss of the hexosamine content of the articular cartilage. These changes were seen as early as after 24 h of culture. Activated macrophages therefore release enzymes that can completely destroy cartilage. Both collagenase and a proteoglycan-hydrolyzing enzyme are released which in vivo might be responsible for the cartilage damage that is found in diseases such as rheumatoid arthritis.", "contents": "Breakdown of articular cartilage proteoglycans by lymphokine-activated macrophages. Lymphokine supernatants (LE) prepared from antigen sensitive lymphocytes caused an inhibition of migration of macrophages from capillary tubes. Control supernatants (LC) had no effect. The lymphokine supernatants, when added to macrophage cultures (the equivalent of 60 x 10(6) lymphocytes added to 40 x 10(6) macrophages), activated the macrophages so that they secreted the enzyme collagenase after 48 h and 72 h of culture. No collagenase was detected before 48 h or from macrophage supernatants to which LC was added. The macrophage supernatants (LE but not LC) also contained factors (probably enzymes) that, when added to a piece of articular cartilage in medium, caused a partial loss of the hexosamine content of the articular cartilage. These changes were seen as early as after 24 h of culture. Activated macrophages therefore release enzymes that can completely destroy cartilage. Both collagenase and a proteoglycan-hydrolyzing enzyme are released which in vivo might be responsible for the cartilage damage that is found in diseases such as rheumatoid arthritis."}
{"id": "PMID:216635", "title": "Systematics: use of protein nearest neighbour frequency distribution as an objective key.", "content": "Although it is one of the oldest of modern disciplines, systematics has always been a science practised in a highly personalised and subjective way because of the need to rely on morphological characteristics of the living organisms, as well as the fossil remains, for their classification. Recent studies on the amino acid nearest neighbours, however, enable one to have an objective key for classifying organisms as well as their relationships.", "contents": "Systematics: use of protein nearest neighbour frequency distribution as an objective key. Although it is one of the oldest of modern disciplines, systematics has always been a science practised in a highly personalised and subjective way because of the need to rely on morphological characteristics of the living organisms, as well as the fossil remains, for their classification. Recent studies on the amino acid nearest neighbours, however, enable one to have an objective key for classifying organisms as well as their relationships."}
{"id": "PMID:216636", "title": "Computerised measures of electro-oculographic activity during sleep.", "content": "Since electro-oculographic (EOG) activity during human sleep appears to be of medical diagnostic and prognostic value, the vast amount of EOG data representative of even a single night's sleep warrants the development of automated pattern recognition and information extraction techniques. Such a technique for the analysis of sleep EOG rapid eye movement (REM) is presented in which the time of occurrence, area, height, duration and binocular symphrony for each REM are measured. This automated technique for sleep EOG analysis is currently used in the investigation of periodicities and values of REM parameters for normal subjects and in the differential diagnosis of affective disorders.", "contents": "Computerised measures of electro-oculographic activity during sleep. Since electro-oculographic (EOG) activity during human sleep appears to be of medical diagnostic and prognostic value, the vast amount of EOG data representative of even a single night's sleep warrants the development of automated pattern recognition and information extraction techniques. Such a technique for the analysis of sleep EOG rapid eye movement (REM) is presented in which the time of occurrence, area, height, duration and binocular symphrony for each REM are measured. This automated technique for sleep EOG analysis is currently used in the investigation of periodicities and values of REM parameters for normal subjects and in the differential diagnosis of affective disorders."}
{"id": "PMID:216637", "title": "Automatic REM detection: modifications on an existing system and preliminary normative data.", "content": "This paper describes hardware changes and additions to a previously reported sleep rapid eye movement (REM) automatic detection system. Specifically, it describes the design philosophy of a new and optimum analogue bandpass prefilter, new detection criteria based on a detailed study of the waveform distortion due to AC coupling and bandpass prefiltering and the implementation of an artifact detection system for a more accurate detection of seemingly REM-related electro-oculographic (EOG) waveforms. Preliminary normative data on phasic REM patterns from young adults, detected by the described system, are also presented.", "contents": "Automatic REM detection: modifications on an existing system and preliminary normative data. This paper describes hardware changes and additions to a previously reported sleep rapid eye movement (REM) automatic detection system. Specifically, it describes the design philosophy of a new and optimum analogue bandpass prefilter, new detection criteria based on a detailed study of the waveform distortion due to AC coupling and bandpass prefiltering and the implementation of an artifact detection system for a more accurate detection of seemingly REM-related electro-oculographic (EOG) waveforms. Preliminary normative data on phasic REM patterns from young adults, detected by the described system, are also presented."}
{"id": "PMID:216639", "title": "A comparison of the prognostic value of antibody-dependent lymphocyte cytotoxicity and other EBV antibody assays in Chinese patients with nasopharyngeal carcinoma.", "content": "Antibody titres to EBV-associated antigens in Chinese NPC patients were analysed according to length of survival after diagnosis and to disease stage. Geometric mean titres of ADLC antibody were highest in the long-term survivors, whereas VCA, EA and EBNA antibody titres showed an inverse relationship to survival. High VCA, EA and EBNA titres were less frequent, and high ADLC titres were more frequent in long-term survivors than in intermediate or short-term survivors. The association of geometric mean titres of EBV antibodies with prognosis could not be entirely explained by stage of disease. A functional role for the ADLC antibody is suggested by the association of a high ADLC antibody titre with a good prognosis regardless of stage of disease.", "contents": "A comparison of the prognostic value of antibody-dependent lymphocyte cytotoxicity and other EBV antibody assays in Chinese patients with nasopharyngeal carcinoma. Antibody titres to EBV-associated antigens in Chinese NPC patients were analysed according to length of survival after diagnosis and to disease stage. Geometric mean titres of ADLC antibody were highest in the long-term survivors, whereas VCA, EA and EBNA antibody titres showed an inverse relationship to survival. High VCA, EA and EBNA titres were less frequent, and high ADLC titres were more frequent in long-term survivors than in intermediate or short-term survivors. The association of geometric mean titres of EBV antibodies with prognosis could not be entirely explained by stage of disease. A functional role for the ADLC antibody is suggested by the association of a high ADLC antibody titre with a good prognosis regardless of stage of disease."}
{"id": "PMID:216641", "title": "Differences in EBV receptor concentration between in vitro EBV-converted lymphoma sublines reflect biological differences between the converting viral substrains.", "content": "We have compared the EBV-receptor concentration of two originally EBV-negative human B-cell lymphoma lines, after in vitro conversion with the transforming B95-8 or the cytopathic P3HR-1 EB-viral substrain, respectively, into permanent EBV-carrying sublines. Receptors were measured by the quantitative EBV-absorption bioassay of Sairenji and Hinuma (1973). EBV receptor concentration of all P3HR-1 virus-converted sublines was significantly reduced, in comparison with the B95-8 virus-converted sublines. This suggests that cells with a low receptor concentration are more likely to survive the initial infection with the P3HR-1 viral harvest. The results further confirm the biological differences between the two EBV substrains.", "contents": "Differences in EBV receptor concentration between in vitro EBV-converted lymphoma sublines reflect biological differences between the converting viral substrains. We have compared the EBV-receptor concentration of two originally EBV-negative human B-cell lymphoma lines, after in vitro conversion with the transforming B95-8 or the cytopathic P3HR-1 EB-viral substrain, respectively, into permanent EBV-carrying sublines. Receptors were measured by the quantitative EBV-absorption bioassay of Sairenji and Hinuma (1973). EBV receptor concentration of all P3HR-1 virus-converted sublines was significantly reduced, in comparison with the B95-8 virus-converted sublines. This suggests that cells with a low receptor concentration are more likely to survive the initial infection with the P3HR-1 viral harvest. The results further confirm the biological differences between the two EBV substrains."}
{"id": "PMID:216640", "title": "Antibody responses to Herpesvirus papio antigens in baboons with lymphoma.", "content": "An Epstein-Barr virus-related herpesvirus, termed Herpesvirus papio (HVP), was isolated from baboons (Papio hamadryas) at the Institute of Experimental Pathology and Therapy, Sukhumi, USSR, where there is a continuing outbreak of lymphoma. In the present study sera from diseased baboons and from age- and sex-matched control animals were examined for antibodies to HVP antigens. Results showed that animals with lymphoid disease had antibodies to HVP virus capsid, early, soluble, and nuclear antigens at higher frequencies and at higher titers than did control animals. Antibody titers were not age- or sex-related. No concordancy was detected for antibodies to soluble and nuclear antigens. The sera were also examined for antibodies to two other widely distributed viruses of hamadryas baboons, cytomegalovirus and foamy virus. The results of these studies did not indicate a disease-related role for either of these viruses.", "contents": "Antibody responses to Herpesvirus papio antigens in baboons with lymphoma. An Epstein-Barr virus-related herpesvirus, termed Herpesvirus papio (HVP), was isolated from baboons (Papio hamadryas) at the Institute of Experimental Pathology and Therapy, Sukhumi, USSR, where there is a continuing outbreak of lymphoma. In the present study sera from diseased baboons and from age- and sex-matched control animals were examined for antibodies to HVP antigens. Results showed that animals with lymphoid disease had antibodies to HVP virus capsid, early, soluble, and nuclear antigens at higher frequencies and at higher titers than did control animals. Antibody titers were not age- or sex-related. No concordancy was detected for antibodies to soluble and nuclear antigens. The sera were also examined for antibodies to two other widely distributed viruses of hamadryas baboons, cytomegalovirus and foamy virus. The results of these studies did not indicate a disease-related role for either of these viruses."}
{"id": "PMID:216642", "title": "Azathioprine-induced lymphocytic neoplasms of NZB mice lack ecotropic murine leukaemia virus.", "content": "NZB mice injected intramuscularly throughout a 6-month period with the immunosuppressant azathioprine (Imuran) developed lymphocytic lymphomas 6--7 months after treatment was initiated. These malignancies were quite distinct from the reticulum-cell neoplasia which occurs spontaneously in the strain, and were readily transplantable to NZB or histocompatible BALB/c recipients. Xenotropic, but not ecotropic murine leukaemia virus (MuLV) was detected in leukaemic tissues of some donor and recipient NZBs when tested in vitro by co-cultivation with permissive cell lines, genome rescue, XC and viral polymerase assays. Virus filtrates prepared from donor leukaemic tissues were non-pathogenic when injected into newborn C3H mice. These results are evidence against a mandatory ecotropic MuLV genome in lymphocytic neoplasia.", "contents": "Azathioprine-induced lymphocytic neoplasms of NZB mice lack ecotropic murine leukaemia virus. NZB mice injected intramuscularly throughout a 6-month period with the immunosuppressant azathioprine (Imuran) developed lymphocytic lymphomas 6--7 months after treatment was initiated. These malignancies were quite distinct from the reticulum-cell neoplasia which occurs spontaneously in the strain, and were readily transplantable to NZB or histocompatible BALB/c recipients. Xenotropic, but not ecotropic murine leukaemia virus (MuLV) was detected in leukaemic tissues of some donor and recipient NZBs when tested in vitro by co-cultivation with permissive cell lines, genome rescue, XC and viral polymerase assays. Virus filtrates prepared from donor leukaemic tissues were non-pathogenic when injected into newborn C3H mice. These results are evidence against a mandatory ecotropic MuLV genome in lymphocytic neoplasia."}
{"id": "PMID:216644", "title": "Prevention of spontaneous leukemia in mice by oncornavirus immunization.", "content": "C57L, NIH, and SWR mice were immunized with inactivated Gross leukemia virus (GLV) and then mated with AKR males. Their F1 offspring were then immunized with the murine sarcoma virus pseudotype of GLV, MSV(GLV). The concentrations of infectious ecotropic AKR virus in tail extracts of immunized mice were 100- to 1,000-fold lower than in non-immunized controls when tested at 30--40 days of age. Although viral titers increased slightly with time, the titers remained at least one log10 lower in the immunized mice than in non-immunized F1 control mice at all times tested. The reduction in the level of expression of endogenous ecotropic virus showed a highly significant positive correlation with the reduction in incidence of spontaneous leukemia in these mice. These data thus show that successful immunoprevention of leukemia in mice can be achieved with viral vaccines.", "contents": "Prevention of spontaneous leukemia in mice by oncornavirus immunization. C57L, NIH, and SWR mice were immunized with inactivated Gross leukemia virus (GLV) and then mated with AKR males. Their F1 offspring were then immunized with the murine sarcoma virus pseudotype of GLV, MSV(GLV). The concentrations of infectious ecotropic AKR virus in tail extracts of immunized mice were 100- to 1,000-fold lower than in non-immunized controls when tested at 30--40 days of age. Although viral titers increased slightly with time, the titers remained at least one log10 lower in the immunized mice than in non-immunized F1 control mice at all times tested. The reduction in the level of expression of endogenous ecotropic virus showed a highly significant positive correlation with the reduction in incidence of spontaneous leukemia in these mice. These data thus show that successful immunoprevention of leukemia in mice can be achieved with viral vaccines."}
{"id": "PMID:216649", "title": "Chemotactic activity and cellular infiltration of aqueous humor in experimental herpes simplex uveitis.", "content": "The degree of chemotactic activity of the aqueous humor for a specific type of inflammatory cell is in direct proportion to the extent of such cells infiltrating the aqueous humor of rabbits with either primary or secondary experimental herpes simplex uveitis. Chemotaxis may thus be a contributing factor in the pathogenesis of herpetic uveitis.", "contents": "Chemotactic activity and cellular infiltration of aqueous humor in experimental herpes simplex uveitis. The degree of chemotactic activity of the aqueous humor for a specific type of inflammatory cell is in direct proportion to the extent of such cells infiltrating the aqueous humor of rabbits with either primary or secondary experimental herpes simplex uveitis. Chemotaxis may thus be a contributing factor in the pathogenesis of herpetic uveitis."}
{"id": "PMID:216646", "title": "Herpetic whitlow.", "content": "Three patients with herpetic whitlow are presented. Virus typing revealed herpes simplex virus type 1 in two and type 2 in one of the cases. There is a high risk of infection among medical personnel.", "contents": "Herpetic whitlow. Three patients with herpetic whitlow are presented. Virus typing revealed herpes simplex virus type 1 in two and type 2 in one of the cases. There is a high risk of infection among medical personnel."}
{"id": "PMID:216645", "title": "The glucagonoma syndrome.", "content": "The glucagonoma syndrome is another of those systemic disorders in which skin manifestations provide a clue to the diagnosis. The patient will most often be a middle-aged woman who has the characteristic, indolent skin lesions in the face of diabetes mellitus and additional features to suggest an occult carcinoma. Marked elevation of the levels of plasma glucagon should confirm the suspicion cure of the skin lesions follows cure of the tumor. Two lines of speculation seem promising. Either the initial event is an overproduction of glucagon and all other observations follow. Or the syndrome is another of the polyendocrine disorders. Cases are still too few to resolve either the pathophysiology, prognosis, or even to guess at the true frequency of the syndrome.", "contents": "The glucagonoma syndrome. The glucagonoma syndrome is another of those systemic disorders in which skin manifestations provide a clue to the diagnosis. The patient will most often be a middle-aged woman who has the characteristic, indolent skin lesions in the face of diabetes mellitus and additional features to suggest an occult carcinoma. Marked elevation of the levels of plasma glucagon should confirm the suspicion cure of the skin lesions follows cure of the tumor. Two lines of speculation seem promising. Either the initial event is an overproduction of glucagon and all other observations follow. Or the syndrome is another of the polyendocrine disorders. Cases are still too few to resolve either the pathophysiology, prognosis, or even to guess at the true frequency of the syndrome."}
{"id": "PMID:216652", "title": "Growth failure from symptomless celiac disease. A study of 14 patients.", "content": "In 14 children and adolescents, abnormally short stature was shown to be due to celiac disease (CD) though the patients had no current gastrointestinal symptoms. Growth failure had appeared in the first years of life, and was associated with a marked lag in bone age. Subnormal growth hormone (GH) responses were demonstrated in 4 patients, and subnormal ACTH responses in 2. In 1 patient permanent isolated GH deficiency coincided with CD. A jejunal biopsy should form part of the routine diagnostic evaluation for abnormally short stature, except in patients who have had normal growth during the first year of life.", "contents": "Growth failure from symptomless celiac disease. A study of 14 patients. In 14 children and adolescents, abnormally short stature was shown to be due to celiac disease (CD) though the patients had no current gastrointestinal symptoms. Growth failure had appeared in the first years of life, and was associated with a marked lag in bone age. Subnormal growth hormone (GH) responses were demonstrated in 4 patients, and subnormal ACTH responses in 2. In 1 patient permanent isolated GH deficiency coincided with CD. A jejunal biopsy should form part of the routine diagnostic evaluation for abnormally short stature, except in patients who have had normal growth during the first year of life."}
{"id": "PMID:216653", "title": "Growth retardation and bone mineral status in children with coeliac disease recognized after the age of 3 years.", "content": "Growth data, clinical symptoms and bone mineral parameters were analyzed in 20 children with coeliac disease in whom the diagnosis was established by biopsy at age 3-13 years. Small stature and bone age retardation (greater than 2 SD) were present in 65% and 60%, respectively. Typical clinical symptoms of coeliac disease as found in the younger child were present in many cases, but 3 were completely asymptomatic except for severe growth retardation. Metacarpal diameters and cortical thickness were significantly decreased for chronological age but in most cases normal for bone age. Quantitative bone mineral analysis of the radius by computed tomography revealed normal values for height and weight in the 4 cases investigated. It is concluded that coeliac disease should always be considered in the differential diagnosis of retarded growth and bone age. \"Osteoporosis\" may occur in coeliac disease, but does not necessarily accompany growth failure. The analysis of metacarpal diameters and cortical thickness in the search of \"osteoporosis\" may result in false interpretation if not correlated to height and weight.", "contents": "Growth retardation and bone mineral status in children with coeliac disease recognized after the age of 3 years. Growth data, clinical symptoms and bone mineral parameters were analyzed in 20 children with coeliac disease in whom the diagnosis was established by biopsy at age 3-13 years. Small stature and bone age retardation (greater than 2 SD) were present in 65% and 60%, respectively. Typical clinical symptoms of coeliac disease as found in the younger child were present in many cases, but 3 were completely asymptomatic except for severe growth retardation. Metacarpal diameters and cortical thickness were significantly decreased for chronological age but in most cases normal for bone age. Quantitative bone mineral analysis of the radius by computed tomography revealed normal values for height and weight in the 4 cases investigated. It is concluded that coeliac disease should always be considered in the differential diagnosis of retarded growth and bone age. \"Osteoporosis\" may occur in coeliac disease, but does not necessarily accompany growth failure. The analysis of metacarpal diameters and cortical thickness in the search of \"osteoporosis\" may result in false interpretation if not correlated to height and weight."}
{"id": "PMID:216654", "title": "The light microscopic demonstration of hydroperoxidase-positive Phi bodies and rods in leukocytes in acute myeloid leukemia.", "content": "Unique fusiform or spindle-shaped particles (Phi bodies) and rods with hydroperoxidase (catalase and/or peroxidase) activity are present in human granulocyte precursors only in acute myelogenous leukemia (AML). These newly recognized particles are much more numerous and prominent than Auer rods. They may be rapidly and readily identified using the microscope in marrow or peripheral blood films when the procedures recommended in this paper for fixation, incubation for hydroperoxidase demonstration in 3,3'-diaminobenzidine (DAB)/H2O2 medium, copper salt treatment and counterstaining (optional) with the Papanicolaou method are employed. Films prepared in the same manner but treated with benzidine/H2O2 medium for myeloperoxidase did not reveal these particles. We believe that Phi bodies are pathognomonic of AML since they are almost invariably present in AML patients with active disease. Their presence serves to distinguish AML from acute lymphocytic leukemia and from chronic granulocytic leukemia in blast crisis. Since the particles disappear in disease remission and reappear upon relapse, the recommended procedure is not only useful in diagnosis but in guiding therapy. When a very rapid diagnosis is needed, it is not necessary to counterstain the preparations, but the nuclei, cytoplasm and plasmalemma can readily be observed in the granulocyte precursors when they are counterstained by the Papanicolaou method. This treatment does not diminish the clarity of the Phi bodies and rods which stain by virtue of their peroxidatic activity. This cytochemical diagnostic procedure should be considered for adoption by hematology laboratories.", "contents": "The light microscopic demonstration of hydroperoxidase-positive Phi bodies and rods in leukocytes in acute myeloid leukemia. Unique fusiform or spindle-shaped particles (Phi bodies) and rods with hydroperoxidase (catalase and/or peroxidase) activity are present in human granulocyte precursors only in acute myelogenous leukemia (AML). These newly recognized particles are much more numerous and prominent than Auer rods. They may be rapidly and readily identified using the microscope in marrow or peripheral blood films when the procedures recommended in this paper for fixation, incubation for hydroperoxidase demonstration in 3,3'-diaminobenzidine (DAB)/H2O2 medium, copper salt treatment and counterstaining (optional) with the Papanicolaou method are employed. Films prepared in the same manner but treated with benzidine/H2O2 medium for myeloperoxidase did not reveal these particles. We believe that Phi bodies are pathognomonic of AML since they are almost invariably present in AML patients with active disease. Their presence serves to distinguish AML from acute lymphocytic leukemia and from chronic granulocytic leukemia in blast crisis. Since the particles disappear in disease remission and reappear upon relapse, the recommended procedure is not only useful in diagnosis but in guiding therapy. When a very rapid diagnosis is needed, it is not necessary to counterstain the preparations, but the nuclei, cytoplasm and plasmalemma can readily be observed in the granulocyte precursors when they are counterstained by the Papanicolaou method. This treatment does not diminish the clarity of the Phi bodies and rods which stain by virtue of their peroxidatic activity. This cytochemical diagnostic procedure should be considered for adoption by hematology laboratories."}
{"id": "PMID:216655", "title": "Quantitative determination of G6Pase activity in histochemically defined zones of the liver acinus.", "content": "Qualitative histochemical G6Pase distribution patterns obtained with an improved method (Teutsch, 1978) served as the basis for a zonal microdissection of the liver acinus. G6Pase activity was determined quantitatively in tissue samples of zones 1 and 3 by a microfluorometric method (Burch et al., 1978). Using a correlation system it could be demonstrated that the histochemical distribution pattern obtained with the improved method was in better agreement with quantitatively estimated zonal differences of G6Pase activity, both in fed and starved female rats, than with the Wachstein and Meisel medium (1956). From a total of 50 tissue samples analyzed the following average G6Pase activities were calculated: in fed animals 15.36 +/- 3.48 U/g dry weight in zone 1, and 9.28 +/- 2.15 U/g dry weight in zone 3; in starved female rats 42.50 +/- 8.20 U/g dry weight in zone 1, and 29.25 +/- 5.68 U/g dry weight in zone 3. The qualitative histochemical as well as quantitative zonal differences of G6Pase activities are taken as further support for the hypothesis of metabolic zonation of liver parenchyma.", "contents": "Quantitative determination of G6Pase activity in histochemically defined zones of the liver acinus. Qualitative histochemical G6Pase distribution patterns obtained with an improved method (Teutsch, 1978) served as the basis for a zonal microdissection of the liver acinus. G6Pase activity was determined quantitatively in tissue samples of zones 1 and 3 by a microfluorometric method (Burch et al., 1978). Using a correlation system it could be demonstrated that the histochemical distribution pattern obtained with the improved method was in better agreement with quantitatively estimated zonal differences of G6Pase activity, both in fed and starved female rats, than with the Wachstein and Meisel medium (1956). From a total of 50 tissue samples analyzed the following average G6Pase activities were calculated: in fed animals 15.36 +/- 3.48 U/g dry weight in zone 1, and 9.28 +/- 2.15 U/g dry weight in zone 3; in starved female rats 42.50 +/- 8.20 U/g dry weight in zone 1, and 29.25 +/- 5.68 U/g dry weight in zone 3. The qualitative histochemical as well as quantitative zonal differences of G6Pase activities are taken as further support for the hypothesis of metabolic zonation of liver parenchyma."}
{"id": "PMID:216657", "title": "Expornitic of avian pox in a zoo.", "content": "During a 6-week period at the San Diego Zoo, avian pox occurred in 9 pheasants representing 5 species. Lesions were limited to facial skin and consisted of epithelial cell hyperplasia, secondary inflammatory changes, and intracytoplasmic eosinophilic inclusion bodies which, by electron microscopy, were shown to contain pox virus. The disease was self-limiting in 7 pheasants, but 2 pheasants died. Free-ranging Indian red junglefowl were implicated as the source of the infection.", "contents": "Expornitic of avian pox in a zoo. During a 6-week period at the San Diego Zoo, avian pox occurred in 9 pheasants representing 5 species. Lesions were limited to facial skin and consisted of epithelial cell hyperplasia, secondary inflammatory changes, and intracytoplasmic eosinophilic inclusion bodies which, by electron microscopy, were shown to contain pox virus. The disease was self-limiting in 7 pheasants, but 2 pheasants died. Free-ranging Indian red junglefowl were implicated as the source of the infection."}
{"id": "PMID:216661", "title": "Intracellular cyclic GMP-binding proteins in cellular slime molds.", "content": "The complexity of cyclic GMP-binding activity in the 48,000 X g supernatant of three species of the cellular slime molds (Dictyostelium discoideum, Dictyostelium rosarium, and Polysphondylium violaceum) was studied by gel filtration chromatography on AcA 34 Ultrogel. All these species have in common a cyclic GMP-binding protein of molecular weight of about 2.5 X 10(5) which specifically binds this nucleotide. In addition, Scatchard plots of assays carried out with the 48,000 X g supernatant of these species exhibit cyclic GMP-binding activity with an apparent dissociation constant of about 1 nM. None of the cyclic GMP-binding proteins separated by chromatography on AcA 34 Ultrogel was associated to protein kinase activity stimulation. In view of the cyclic GMP function during chemotactic transduction in the cellular slime molds, the possible molecular function for this 2.5 X 10(5)-dalton cyclic GMP-binding protein is discussed.", "contents": "Intracellular cyclic GMP-binding proteins in cellular slime molds. The complexity of cyclic GMP-binding activity in the 48,000 X g supernatant of three species of the cellular slime molds (Dictyostelium discoideum, Dictyostelium rosarium, and Polysphondylium violaceum) was studied by gel filtration chromatography on AcA 34 Ultrogel. All these species have in common a cyclic GMP-binding protein of molecular weight of about 2.5 X 10(5) which specifically binds this nucleotide. In addition, Scatchard plots of assays carried out with the 48,000 X g supernatant of these species exhibit cyclic GMP-binding activity with an apparent dissociation constant of about 1 nM. None of the cyclic GMP-binding proteins separated by chromatography on AcA 34 Ultrogel was associated to protein kinase activity stimulation. In view of the cyclic GMP function during chemotactic transduction in the cellular slime molds, the possible molecular function for this 2.5 X 10(5)-dalton cyclic GMP-binding protein is discussed."}
{"id": "PMID:216662", "title": "Utilization of D-xylose by wild-type strains of Salmonella typhimurium.", "content": "Enzyme studies of strains of Salmonella typhimurium representing biotypes that utilized D-xylose rapidly (xylose strong) or slowly (xylose weak) showed that they were different in the utilization of D-xylose because the xylose-weak strains were deficient in the transport of D-xylose. This observation is consistent with the idea that strains of the different xylose-weak biotypes, e.g. biotypes 17 to 32, were descended from strains of xylose-strong types, particularly from biotype 1.", "contents": "Utilization of D-xylose by wild-type strains of Salmonella typhimurium. Enzyme studies of strains of Salmonella typhimurium representing biotypes that utilized D-xylose rapidly (xylose strong) or slowly (xylose weak) showed that they were different in the utilization of D-xylose because the xylose-weak strains were deficient in the transport of D-xylose. This observation is consistent with the idea that strains of the different xylose-weak biotypes, e.g. biotypes 17 to 32, were descended from strains of xylose-strong types, particularly from biotype 1."}
{"id": "PMID:216663", "title": "Growth of the photosynthetic bacterium Rhodopseudomonas capsulata chemoautotrophically in darkness with H2 as the energy source.", "content": "The phototrophic bacterium Rhodopseudomonas capsulata was found to be capable of growing chemoautotrophically under aerobic conditions in darkness. Growth was strictly dependent on the presence of H2 as the source of energy and reducing power, O2 as the terminal electron acceptor for energy transduction, and CO2 as the sole carbon source; under optimal conditions the generation time was about 6 h. Chemoautotrophically grown cells showed a relatively high content of bacteriochlorophyll a and intracytoplasmic membranes (chromatophores). Experiments with various mutants of R. capsulata, affected in electron transport, indicate that either of the two terminal oxidases of this bacterium can participate in the energy-yielding oxidation of H2. The ability of R. capsulata to multiply in at least five different physiological growth modes suggests that it is one of the most metabolically versatile procaryotes known.", "contents": "Growth of the photosynthetic bacterium Rhodopseudomonas capsulata chemoautotrophically in darkness with H2 as the energy source. The phototrophic bacterium Rhodopseudomonas capsulata was found to be capable of growing chemoautotrophically under aerobic conditions in darkness. Growth was strictly dependent on the presence of H2 as the source of energy and reducing power, O2 as the terminal electron acceptor for energy transduction, and CO2 as the sole carbon source; under optimal conditions the generation time was about 6 h. Chemoautotrophically grown cells showed a relatively high content of bacteriochlorophyll a and intracytoplasmic membranes (chromatophores). Experiments with various mutants of R. capsulata, affected in electron transport, indicate that either of the two terminal oxidases of this bacterium can participate in the energy-yielding oxidation of H2. The ability of R. capsulata to multiply in at least five different physiological growth modes suggests that it is one of the most metabolically versatile procaryotes known."}
{"id": "PMID:216664", "title": "Characterization of pyrimidine-repressible and arginine-repressible carbamyl phosphate synthetases from Bacillus subtilis.", "content": "The number and properties of carbamyl phosphate synthetases in Bacillus subtilis have been uncertain because of conflicting genetic results and instability of the enzyme in extracts. The discovery of a previously unrecognized requirement of B. subtilis carbamyl phosphate synthetases for a high concentration of potassium ions for activity and stability permitted unequivocal demonstration that this bacterium elaborates two carbamyl phosphate synthetases. Carbamyl phosphate synthetase A was shown to be repressed by arginine, to have a molecular weight of about 200,000, and to be coded for by a gene that maps near argC4. This isozyme was insensitive to metabolites of the arginine and pyrimidine biosynthetic pathways. Carbamyl phosphate synthetase P was found to be repressed by uracil, to have a molecular weight of 90,000 to 100,000, and to be coded for by a gene that maps near the other pyr genes. This isozyme was activated by phosphoridine nucleotides. Other kinetic properties of the two isozymes were compared. Bacillus thus resembles eucaryotic microbes in producing two carbamyl phosphate synthetases, rather than the enteric bacteria, which produce a single carbamyl phosphate synthetase.", "contents": "Characterization of pyrimidine-repressible and arginine-repressible carbamyl phosphate synthetases from Bacillus subtilis. The number and properties of carbamyl phosphate synthetases in Bacillus subtilis have been uncertain because of conflicting genetic results and instability of the enzyme in extracts. The discovery of a previously unrecognized requirement of B. subtilis carbamyl phosphate synthetases for a high concentration of potassium ions for activity and stability permitted unequivocal demonstration that this bacterium elaborates two carbamyl phosphate synthetases. Carbamyl phosphate synthetase A was shown to be repressed by arginine, to have a molecular weight of about 200,000, and to be coded for by a gene that maps near argC4. This isozyme was insensitive to metabolites of the arginine and pyrimidine biosynthetic pathways. Carbamyl phosphate synthetase P was found to be repressed by uracil, to have a molecular weight of 90,000 to 100,000, and to be coded for by a gene that maps near the other pyr genes. This isozyme was activated by phosphoridine nucleotides. Other kinetic properties of the two isozymes were compared. Bacillus thus resembles eucaryotic microbes in producing two carbamyl phosphate synthetases, rather than the enteric bacteria, which produce a single carbamyl phosphate synthetase."}
{"id": "PMID:216665", "title": "Some regulation profiles of ornithine transcarbamylase synthesis in vitro.", "content": "The regulation profiles of OTCase (argF, argI) synthesis in vitro were investigated by using the in vitro system described in the accompanying paper. Addition of 2.6 mM arginine, crude repressor and partially purified repressor to the in vitro system demonstrated that lambdadargF-DNA-directed OTCase-FFF synthesis is more sensitive to the repressor than lambdapargI-DNA-directed OTCase-III synthesis. The effects of some low-molecular substances on FFF and III syntheses were investigated; guanosine 3'-diphosphate 5'-diphosphate (ppGpp) stimulated both syntheses while cAMP and guanosine 5'-tetraphosphate (Gpppp) were not effective on III synthesis and were slightly inhibitory for FFF synthesis. The substances had no effect on the maturation of the enzyme or on the activity of the enzyme, FFF or III, synthesized. We suggest that argF- and argI-genes are regulated in a slightly different fashion and that the operator-promotor regions are not completely identical for these two genes.", "contents": "Some regulation profiles of ornithine transcarbamylase synthesis in vitro. The regulation profiles of OTCase (argF, argI) synthesis in vitro were investigated by using the in vitro system described in the accompanying paper. Addition of 2.6 mM arginine, crude repressor and partially purified repressor to the in vitro system demonstrated that lambdadargF-DNA-directed OTCase-FFF synthesis is more sensitive to the repressor than lambdapargI-DNA-directed OTCase-III synthesis. The effects of some low-molecular substances on FFF and III syntheses were investigated; guanosine 3'-diphosphate 5'-diphosphate (ppGpp) stimulated both syntheses while cAMP and guanosine 5'-tetraphosphate (Gpppp) were not effective on III synthesis and were slightly inhibitory for FFF synthesis. The substances had no effect on the maturation of the enzyme or on the activity of the enzyme, FFF or III, synthesized. We suggest that argF- and argI-genes are regulated in a slightly different fashion and that the operator-promotor regions are not completely identical for these two genes."}
{"id": "PMID:216666", "title": "Studies on 15-hydroxyprostaglandin dehydrogenase with various prostaglandin analogues.", "content": "The NAD+-linked 15-hydroxyprostaglandin dehydrogenase (PGDH) of swine lung was purified to a high specific activity by affinity chromatographies on prostaglandin (PG)-and NAD+-Sepharose. The affinities of the enzyme for various synthetic analogues of PGA, E, F, and I and their inhibitory effects on the enzymatic reaction were examined. The modification of the alkyl side chain of PG, particularly at C-15 or C-16, reduced the affinity of the enzyme for these PG analogues. Furthermore, 14-methyl-13,14-dihydro-PGE1 and 16-cyclopentyl-omega-trinor-15-epi-PGE2 were potent inhibitors of PGDH.", "contents": "Studies on 15-hydroxyprostaglandin dehydrogenase with various prostaglandin analogues. The NAD+-linked 15-hydroxyprostaglandin dehydrogenase (PGDH) of swine lung was purified to a high specific activity by affinity chromatographies on prostaglandin (PG)-and NAD+-Sepharose. The affinities of the enzyme for various synthetic analogues of PGA, E, F, and I and their inhibitory effects on the enzymatic reaction were examined. The modification of the alkyl side chain of PG, particularly at C-15 or C-16, reduced the affinity of the enzyme for these PG analogues. Furthermore, 14-methyl-13,14-dihydro-PGE1 and 16-cyclopentyl-omega-trinor-15-epi-PGE2 were potent inhibitors of PGDH."}
{"id": "PMID:216667", "title": "Reaction of cytochrome c with nitrite and nitric oxide. A model of dissimilatory nitrite reductase.", "content": "The reaction of bovine heart ferrocytochrome c with nitrite was studied under various conditions. The reaction product was ferricytochrome c at around pH 5, whereas at around pH 3 it was Compound I, characterized by twin peaks at 529 and 563 nm of equal intensity. However, ferrocytochrome c decreased obeying first-order kinetics over the pH range examined, irrespective of the presence or absence of molecular oxygen. The apparent first-order rate constant was proportional to the square of the nitrite concentration at pH 4.4 and it increased as the pH was lowered. At pH 3 the reaction was so rapid that it had to be followed by stopped-flow and rapid-scanning techniques. The apparent rate constant at this pH was found to increase linearly with the nitrite concentration. Based on these results the active species of nitrite was concluded to be dinitrogen trioxide at pH 4.4 and nitrosonium ion, no+, at pH 3. Compound II was formed by reaction of ferrocytochrome c and NO gas at acidic and alkaline pH values. The absorption peaks were at 533 and 563 nm at pH 3, and at 538 and 567 nm at pH 12.9. This compound was also formed by reducing Compound I with reductants. Compound I prepared from ferricytochrome c and NO was stable below pH 6. However, appreciable absorption peaks for ferrocytochrome c appeared between pH 8 and 10, because Compound I was dissociated into ferrocytochrome c and NO+, and because ferrocytochrome c thus formed reacted with NO very slowly in this pH region. Saccharomyces ferricytochrome c under NO gas behaved differently from mammalian cytochrome, indicating the significance of the nature of the heme environment in determing the reactivity. Only at extreme pH values was Compound II formed exclusively and persisted. A model system for dissimilatory nitrite reductase was constructed by using bovine heart cytochrome c, nitrite and NADH plus PMS at pH 3.3, and a scheme involving cyclic turnover of ferrocytochrome c, Compound I and Compound II is presented, with kinetic parameters.", "contents": "Reaction of cytochrome c with nitrite and nitric oxide. A model of dissimilatory nitrite reductase. The reaction of bovine heart ferrocytochrome c with nitrite was studied under various conditions. The reaction product was ferricytochrome c at around pH 5, whereas at around pH 3 it was Compound I, characterized by twin peaks at 529 and 563 nm of equal intensity. However, ferrocytochrome c decreased obeying first-order kinetics over the pH range examined, irrespective of the presence or absence of molecular oxygen. The apparent first-order rate constant was proportional to the square of the nitrite concentration at pH 4.4 and it increased as the pH was lowered. At pH 3 the reaction was so rapid that it had to be followed by stopped-flow and rapid-scanning techniques. The apparent rate constant at this pH was found to increase linearly with the nitrite concentration. Based on these results the active species of nitrite was concluded to be dinitrogen trioxide at pH 4.4 and nitrosonium ion, no+, at pH 3. Compound II was formed by reaction of ferrocytochrome c and NO gas at acidic and alkaline pH values. The absorption peaks were at 533 and 563 nm at pH 3, and at 538 and 567 nm at pH 12.9. This compound was also formed by reducing Compound I with reductants. Compound I prepared from ferricytochrome c and NO was stable below pH 6. However, appreciable absorption peaks for ferrocytochrome c appeared between pH 8 and 10, because Compound I was dissociated into ferrocytochrome c and NO+, and because ferrocytochrome c thus formed reacted with NO very slowly in this pH region. Saccharomyces ferricytochrome c under NO gas behaved differently from mammalian cytochrome, indicating the significance of the nature of the heme environment in determing the reactivity. Only at extreme pH values was Compound II formed exclusively and persisted. A model system for dissimilatory nitrite reductase was constructed by using bovine heart cytochrome c, nitrite and NADH plus PMS at pH 3.3, and a scheme involving cyclic turnover of ferrocytochrome c, Compound I and Compound II is presented, with kinetic parameters."}
{"id": "PMID:216669", "title": "Inhibition of fructose-1,6-biphosphatase by the photoaffinity AMP analog, 8-azidoadenosine 5'-monophosphate.", "content": "Inhibition studies with the photoreactive AMP analog, 8-azidoadenosine 5'-monophosphate (8-azido-AMP), demonstrate that this compound is, like AMP, an allosteric inhibitor of pig kidney and muscle fructose-1,6-biphosphateses. Photolysis of a mixture of purified pig kidney fructose-1,6-biphosphate and 8-azido-[14C]AMP results in the loss of enzyme activity and the reagent is incorporated to the protein. The incorporation of reagent linearly correlates with the loss of enzyme activity. Extrapolation to zero activity correlates with the incorporation of 3.7 mol of reagent/mol of enzyme (i.e. 0.9 per subunit). Thus, 8-azido-AMP appears to be a photoaffinity label for the allosteric AMP binding site of fructose-1,6-biphosphatase.", "contents": "Inhibition of fructose-1,6-biphosphatase by the photoaffinity AMP analog, 8-azidoadenosine 5'-monophosphate. Inhibition studies with the photoreactive AMP analog, 8-azidoadenosine 5'-monophosphate (8-azido-AMP), demonstrate that this compound is, like AMP, an allosteric inhibitor of pig kidney and muscle fructose-1,6-biphosphateses. Photolysis of a mixture of purified pig kidney fructose-1,6-biphosphate and 8-azido-[14C]AMP results in the loss of enzyme activity and the reagent is incorporated to the protein. The incorporation of reagent linearly correlates with the loss of enzyme activity. Extrapolation to zero activity correlates with the incorporation of 3.7 mol of reagent/mol of enzyme (i.e. 0.9 per subunit). Thus, 8-azido-AMP appears to be a photoaffinity label for the allosteric AMP binding site of fructose-1,6-biphosphatase."}
{"id": "PMID:216670", "title": "Glucagon1-6 binds to the glucagon receptor and activates hepatic adenylate cyclase.", "content": "A fragment of glucagon encompassing its first six NH2-terminal residues (His-Ser-Gln-Gly-Thr-Phe) binds to the glucagon receptor and stimulates adenylate cyclase activity in rat liver plasma membranes. Glucagon1-6 is a partial agonist since it stimulates, at saturating concentrations, to the extent of 75% of the maximal activity given by the native hormone. The binding affinity and potency of glucagon1-6 are 0.001% the native hormone. Discussed are the implications of these findings on the structure-function relationships required for the action of glucagon and for preparing clinically useful analogs of the hormone.", "contents": "Glucagon1-6 binds to the glucagon receptor and activates hepatic adenylate cyclase. A fragment of glucagon encompassing its first six NH2-terminal residues (His-Ser-Gln-Gly-Thr-Phe) binds to the glucagon receptor and stimulates adenylate cyclase activity in rat liver plasma membranes. Glucagon1-6 is a partial agonist since it stimulates, at saturating concentrations, to the extent of 75% of the maximal activity given by the native hormone. The binding affinity and potency of glucagon1-6 are 0.001% the native hormone. Discussed are the implications of these findings on the structure-function relationships required for the action of glucagon and for preparing clinically useful analogs of the hormone."}
{"id": "PMID:216671", "title": "Polyoma virus and cyclic AMP-mediated control of dihydrofolate reductase mRNA abundance in methotrexate-resistant mouse fibroblasts.", "content": "As a model cell culture system for studying polyoma-mediated control of host gene expression, we isolated methotrexate-resistant 3T6 cells in which one of the virus-induced enzymes, dihydrofolate reductase, is a major cellular protein. In highly methotrexate-resistant cell lines dihydrofolate reductase synthesis accounts for over 10% that of soluble portein, corresponding to an increase of approximately 100-fold over the level in parental cells. This increase in dihydrofolate reductase synthesis is due to a corresponding increase in the abundance of dihydrofolate reductase mRNA and gene sequences. We have used these cells to show that infection with polyoma virus results in a 4- to 5-fold increase in the relative rate of dihydrofolate reductase synthesis and a corresponding increase in dihydrofolate reductase mRNA abundance. The increase in dihydrofolate reductase synthesis begins 15 to 20 h after infection and continues to increase until cell lysis. These observations represent the first direct evidence that viral infection of eukaryotic cells results in the increased synthesis of a specific cellular enzyme and an increase in the abundance of a specific cellular mRNA. In order to gain additional insight into the control of dihydrofolate reductase synthesis we examined other parameters affecting dihydrofolate reductase synthesis. We found that the addition of fresh serum to stationary phase cells results in a 2-fold stimulation of dihydrofolate reductase synthesis, beginning 10 to 12 h after serum addition. Serum stimulation of dihydrofolate reductase synthesis is completely inhibited by the presence of dibutyryl cyclic AMP as well as by theophylline or prostaglandin E1, compounds which cause an increase in intracellular cyclic AMP levels. In fact, the presence of dibutyryl cyclic AMP and theophylline results in a 2- to 3-fold decrease in the rate of dihydrofolate reductase synthesis and the abundance of dihydrofolate reductase mRNA. However, in contrast to the effect on serum stimulation, dibutyryl cyclic AMP and theophylline do not inhibit polyoma virus induction of dihydrofolate reductase synthesis or dihydrofolate reductase mRNA levels. These observations suggest that dihydrofolate reductase gene expression is controlled by at least two regulatory pathways: one involving serum that is blocked by high levels of cyclic AMP and another involving polyoma induction that is not inhibited by cyclic AMP.", "contents": "Polyoma virus and cyclic AMP-mediated control of dihydrofolate reductase mRNA abundance in methotrexate-resistant mouse fibroblasts. As a model cell culture system for studying polyoma-mediated control of host gene expression, we isolated methotrexate-resistant 3T6 cells in which one of the virus-induced enzymes, dihydrofolate reductase, is a major cellular protein. In highly methotrexate-resistant cell lines dihydrofolate reductase synthesis accounts for over 10% that of soluble portein, corresponding to an increase of approximately 100-fold over the level in parental cells. This increase in dihydrofolate reductase synthesis is due to a corresponding increase in the abundance of dihydrofolate reductase mRNA and gene sequences. We have used these cells to show that infection with polyoma virus results in a 4- to 5-fold increase in the relative rate of dihydrofolate reductase synthesis and a corresponding increase in dihydrofolate reductase mRNA abundance. The increase in dihydrofolate reductase synthesis begins 15 to 20 h after infection and continues to increase until cell lysis. These observations represent the first direct evidence that viral infection of eukaryotic cells results in the increased synthesis of a specific cellular enzyme and an increase in the abundance of a specific cellular mRNA. In order to gain additional insight into the control of dihydrofolate reductase synthesis we examined other parameters affecting dihydrofolate reductase synthesis. We found that the addition of fresh serum to stationary phase cells results in a 2-fold stimulation of dihydrofolate reductase synthesis, beginning 10 to 12 h after serum addition. Serum stimulation of dihydrofolate reductase synthesis is completely inhibited by the presence of dibutyryl cyclic AMP as well as by theophylline or prostaglandin E1, compounds which cause an increase in intracellular cyclic AMP levels. In fact, the presence of dibutyryl cyclic AMP and theophylline results in a 2- to 3-fold decrease in the rate of dihydrofolate reductase synthesis and the abundance of dihydrofolate reductase mRNA. However, in contrast to the effect on serum stimulation, dibutyryl cyclic AMP and theophylline do not inhibit polyoma virus induction of dihydrofolate reductase synthesis or dihydrofolate reductase mRNA levels. These observations suggest that dihydrofolate reductase gene expression is controlled by at least two regulatory pathways: one involving serum that is blocked by high levels of cyclic AMP and another involving polyoma induction that is not inhibited by cyclic AMP."}
{"id": "PMID:216673", "title": "Human serum albumin. Spectroscopic studies of binding and proximity relationships for fatty acids and bilirubin.", "content": "Binding and proximity relationships of hydrophobic ligands on human serum albumin have been studied using absorption, fluorescence, circular dichroism, and electron paramagnetic resonance spectroscopy. The ligands studied were bilirubin, two conjugated linear polyene fatty acids, cis-parinaric acid and cis-eleostearic acid, and three nitroxide derivatives of stearic acid with doxyl groups at positions 5, 10, and 12, respectively. Binding of polyene fatty acids was monitored by absorption peak shifts, induced circular dichroism, enhancement of fluorescence, and energy transfer between albumin's single tryptophanyl residue and the polyene chromophore. Induced circular dichroism studies indicate excitonic ligand-ligand interaction between bound fatty acids. Fluorescence enhancement of cis-parinaric acid was analyzed using a stepwise multiple equilibrium model, and six binding constants in the range 10(8) to 10(6) M-1 were obtained, in agreement with previous measurements for other fatty acids. The temperature dependence of the equilibrium constants indicates that the binding enthalpy is nearly zero. Fluorescence energy transfer was similarly used to quantitate bilirubin binding to albumin. Energy transfer, nitroxide quenching of fluorescence, and electron paramagnetic resonance spectroscopy were used to elucidate binding geometries which support and extend proposed structural models for albumin. It is suggested that the first two fatty acids bind side-by-side in an antiparallel fashion in domain III of human serum albumin.", "contents": "Human serum albumin. Spectroscopic studies of binding and proximity relationships for fatty acids and bilirubin. Binding and proximity relationships of hydrophobic ligands on human serum albumin have been studied using absorption, fluorescence, circular dichroism, and electron paramagnetic resonance spectroscopy. The ligands studied were bilirubin, two conjugated linear polyene fatty acids, cis-parinaric acid and cis-eleostearic acid, and three nitroxide derivatives of stearic acid with doxyl groups at positions 5, 10, and 12, respectively. Binding of polyene fatty acids was monitored by absorption peak shifts, induced circular dichroism, enhancement of fluorescence, and energy transfer between albumin's single tryptophanyl residue and the polyene chromophore. Induced circular dichroism studies indicate excitonic ligand-ligand interaction between bound fatty acids. Fluorescence enhancement of cis-parinaric acid was analyzed using a stepwise multiple equilibrium model, and six binding constants in the range 10(8) to 10(6) M-1 were obtained, in agreement with previous measurements for other fatty acids. The temperature dependence of the equilibrium constants indicates that the binding enthalpy is nearly zero. Fluorescence energy transfer was similarly used to quantitate bilirubin binding to albumin. Energy transfer, nitroxide quenching of fluorescence, and electron paramagnetic resonance spectroscopy were used to elucidate binding geometries which support and extend proposed structural models for albumin. It is suggested that the first two fatty acids bind side-by-side in an antiparallel fashion in domain III of human serum albumin."}
{"id": "PMID:216674", "title": "Acetate kinase from Veillonella alcalescens. Purification and physical properties.", "content": "Acetate kinase (ATP:phosphotransferase E.C.2.7.2.1) has been purified to a high state of purity from Veillonella alcalescens. The native enzyme had a molecular weight of 88,000, as determined by Sephadex G-150 gel filtration. The molecular weight of the monomeric enzyme, estimated from sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was 42,000. The enzyme was determined to be a homodimer from the amino acid composition and the results of trypsin digestion and cyanogen bromide cleavage. Two moles of phosphate were incorporated into the dimer upon incubation of the enzyme with ATP and acetate. These results support the conclusion that each subunit of the dimeric enzyme consists of a single active catalytic center. Succinate enhanced the rate of ATP-ADP phosphoryl group exchange 20-fold and the binding of ATP 10-fold. These results are considered in light of data from previous reports (Pelroy, R. A., and Whiteley, H. R. (1971) J. Bacteriol. 105, 259-267; Bowman, C. M., Valdez, R. O., and Nishimura, J. S. (1976) J. Biol. Chem 251, 3117-3121).", "contents": "Acetate kinase from Veillonella alcalescens. Purification and physical properties. Acetate kinase (ATP:phosphotransferase E.C.2.7.2.1) has been purified to a high state of purity from Veillonella alcalescens. The native enzyme had a molecular weight of 88,000, as determined by Sephadex G-150 gel filtration. The molecular weight of the monomeric enzyme, estimated from sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was 42,000. The enzyme was determined to be a homodimer from the amino acid composition and the results of trypsin digestion and cyanogen bromide cleavage. Two moles of phosphate were incorporated into the dimer upon incubation of the enzyme with ATP and acetate. These results support the conclusion that each subunit of the dimeric enzyme consists of a single active catalytic center. Succinate enhanced the rate of ATP-ADP phosphoryl group exchange 20-fold and the binding of ATP 10-fold. These results are considered in light of data from previous reports (Pelroy, R. A., and Whiteley, H. R. (1971) J. Bacteriol. 105, 259-267; Bowman, C. M., Valdez, R. O., and Nishimura, J. S. (1976) J. Biol. Chem 251, 3117-3121)."}
{"id": "PMID:216675", "title": "Translation of capped and uncapped vesicular stomatitis virus and reovirus mRNA'S. Sensitivity to m7GpppAm and ionic conditions.", "content": "In an attempt to elucidate the role of the 5'-terminal 7-methylguanosine residue in translation of mammalian mRNAs, vesicular stomatitis virus (VS virus), and reovirus mRNAs containing and lacking this residue, and also Qbeta RNA, were translated in cell-free extracts from reticulocytes and wheat germ under a variety of ionic conditions. Optimal translation of mRNAs lacking a 5' m7G occurred at concentrations of KOAc or KCl which were lower than those optimal for normal \"capped\" mRNAs. However, this salt dependence was much less marked in the mammalian reticulocyte extract and, at salt concentrations optimal for translation of normal capped mRNAs, reticulocyte lysates translated uncapped with mRNAs at 30 to 60% the normal efficiency. At low K+ concentrations, wheat germ ribosomes bound and translated appreciable amounts of uncapped VS virus mRNA; controls showed that no m7G residue is added to the 5' end of the bound RNA. Analogues of the 5' end, such as m7GpppAm, inhibited translation of both normal and uncapped VS virus RNAs in wheat germ extracts to about the same extent, but the efficiency of its action was reduced at low K+ concentrations. We conclude that there is a reduced importance of the 5' m7G residue in ribosome-mRNA recognition at low K+ concentrations, and that translation of mRNAs in reticulocyte extract is, under any reaction conditions, less dependent on the presence of a 5' \"cap\" than in wheat germ extracts.", "contents": "Translation of capped and uncapped vesicular stomatitis virus and reovirus mRNA'S. Sensitivity to m7GpppAm and ionic conditions. In an attempt to elucidate the role of the 5'-terminal 7-methylguanosine residue in translation of mammalian mRNAs, vesicular stomatitis virus (VS virus), and reovirus mRNAs containing and lacking this residue, and also Qbeta RNA, were translated in cell-free extracts from reticulocytes and wheat germ under a variety of ionic conditions. Optimal translation of mRNAs lacking a 5' m7G occurred at concentrations of KOAc or KCl which were lower than those optimal for normal \"capped\" mRNAs. However, this salt dependence was much less marked in the mammalian reticulocyte extract and, at salt concentrations optimal for translation of normal capped mRNAs, reticulocyte lysates translated uncapped with mRNAs at 30 to 60% the normal efficiency. At low K+ concentrations, wheat germ ribosomes bound and translated appreciable amounts of uncapped VS virus mRNA; controls showed that no m7G residue is added to the 5' end of the bound RNA. Analogues of the 5' end, such as m7GpppAm, inhibited translation of both normal and uncapped VS virus RNAs in wheat germ extracts to about the same extent, but the efficiency of its action was reduced at low K+ concentrations. We conclude that there is a reduced importance of the 5' m7G residue in ribosome-mRNA recognition at low K+ concentrations, and that translation of mRNAs in reticulocyte extract is, under any reaction conditions, less dependent on the presence of a 5' \"cap\" than in wheat germ extracts."}
{"id": "PMID:216676", "title": "Islet-activating protein. Enhanced insulin secretion and cyclic AMP accumulation in pancreatic islets due to activation of native calcium ionophores.", "content": "The mechanism whereby \"islet-activating protein\" (IAP) purified from the culture medium of Bordetella pertussis potentiates insulin secretion was studied by experiments in vitro with islets of rats once injected with IAP (0.5 micrograms/100 g body weight, 3 days before killing) or with islets that had been exposed to IAP (0.1 to 100 ng/ml) for 24 h. The IAP treatment markedly enhanced insulin secretory responses and cAMP accumulation in islets, facilitated the efflux of 45Ca through the cell membrane, and abolished the alpha-adrenergic action of epinephrine (and somatostatin) to inhibit glucose-induced insulin release, cAMP accumulation, and 45Ca uptake. These effects of the IAP treatment were reduced when islets were incubated in a low calcium medium. Based on these results, it was concluded that IAP interacts directly but slowly with the islet B cell in such a manner as to render more calcium available to the stimulus-secretion coupling mechanism as a result of sustained activation of native calcium ionophores on the cell membrane.", "contents": "Islet-activating protein. Enhanced insulin secretion and cyclic AMP accumulation in pancreatic islets due to activation of native calcium ionophores. The mechanism whereby \"islet-activating protein\" (IAP) purified from the culture medium of Bordetella pertussis potentiates insulin secretion was studied by experiments in vitro with islets of rats once injected with IAP (0.5 micrograms/100 g body weight, 3 days before killing) or with islets that had been exposed to IAP (0.1 to 100 ng/ml) for 24 h. The IAP treatment markedly enhanced insulin secretory responses and cAMP accumulation in islets, facilitated the efflux of 45Ca through the cell membrane, and abolished the alpha-adrenergic action of epinephrine (and somatostatin) to inhibit glucose-induced insulin release, cAMP accumulation, and 45Ca uptake. These effects of the IAP treatment were reduced when islets were incubated in a low calcium medium. Based on these results, it was concluded that IAP interacts directly but slowly with the islet B cell in such a manner as to render more calcium available to the stimulus-secretion coupling mechanism as a result of sustained activation of native calcium ionophores on the cell membrane."}
{"id": "PMID:216677", "title": "Separation of vesicles of cardiac sarcolemma from vesicles of cardiac sarcoplasmic reticulum. Comparative biochemical analysis of component activities.", "content": "Sarcolemmal and sarcoplasmic reticulum membrane vesicle fractions were isolated from cardiac microsomes. Separation of sarcolemmal and sarcoplasmic reticulum membrane markers was documented by a combination of correlative assay and centrifugation techniques. To facilitate the separation, the crude microsomes were incubated in the presence of ATP, Ca2+, and oxalate to increase the density of the sarcoplasmic reticulum vesicles. After sucrose gradient centrifugation, the densest subfraction (sarcoplasmic reticulum) contained the highest (K+,Ca2+)-ATPase activity and virtually no (Na2+,K+)-ATPase activity, even when latent (Na+,K+)-ATPase activity was unmasked. In addition, the sarcoplasmic reticulum fraction contained no significant sialic acid, beta receptor binding activity, or adenylate cyclase activity. Sarcolemmal membrane fractions were of low buoyant density. Preparations most enriched in sarcolemmal vesicles contained the highest level of all the other parameters and only about 10% of the (K+,Ca2+)-ATPase activity of the sarcoplasmic reticulum fraction. The results suggest that (Na+,K+)-ATPase, sialic acid, beta-adrenergic receptors, and adenylate cyclase can be entirely accounted for by the sarcolemmal content of cardiac microsomes. Gel electrophoresis of the sarcolemmal and sarcoplasmic reticulum membrane fractions showed distinct bands. Membrane proteins exclusive to each of the fractions were also demonstrated by phosphorylation. Cyclic AMP stimulated phosphorylation by [gamma-32P]ATP of two proteins of apparent Mr = 20,000 and 7,000 that were concentrated in sarcoplasmic reticulum, but the stimulation was markedly dependent on the presence of added soluble cyclic AMP-dependent protein kinase. Cyclic AMP also stimulated phosphorylation of membrane proteins in sarcolemma, but this phosphorylation was mediated by an endogenous protein kinase activity. The apparent molecular weights of these phosphorylated proteins were 165,000, 90,000, 56,000, 24,000, and 11,000. The results suggest that sarcolemma may contain an integral enzyme complex, not present in sarcoplasmic reticulum, that contains beta-adrenergic receptors, adenylate cyclase, cyclic AMP-dependent protein kinase, and several substrates of the protein kinase.", "contents": "Separation of vesicles of cardiac sarcolemma from vesicles of cardiac sarcoplasmic reticulum. Comparative biochemical analysis of component activities. Sarcolemmal and sarcoplasmic reticulum membrane vesicle fractions were isolated from cardiac microsomes. Separation of sarcolemmal and sarcoplasmic reticulum membrane markers was documented by a combination of correlative assay and centrifugation techniques. To facilitate the separation, the crude microsomes were incubated in the presence of ATP, Ca2+, and oxalate to increase the density of the sarcoplasmic reticulum vesicles. After sucrose gradient centrifugation, the densest subfraction (sarcoplasmic reticulum) contained the highest (K+,Ca2+)-ATPase activity and virtually no (Na2+,K+)-ATPase activity, even when latent (Na+,K+)-ATPase activity was unmasked. In addition, the sarcoplasmic reticulum fraction contained no significant sialic acid, beta receptor binding activity, or adenylate cyclase activity. Sarcolemmal membrane fractions were of low buoyant density. Preparations most enriched in sarcolemmal vesicles contained the highest level of all the other parameters and only about 10% of the (K+,Ca2+)-ATPase activity of the sarcoplasmic reticulum fraction. The results suggest that (Na+,K+)-ATPase, sialic acid, beta-adrenergic receptors, and adenylate cyclase can be entirely accounted for by the sarcolemmal content of cardiac microsomes. Gel electrophoresis of the sarcolemmal and sarcoplasmic reticulum membrane fractions showed distinct bands. Membrane proteins exclusive to each of the fractions were also demonstrated by phosphorylation. Cyclic AMP stimulated phosphorylation by [gamma-32P]ATP of two proteins of apparent Mr = 20,000 and 7,000 that were concentrated in sarcoplasmic reticulum, but the stimulation was markedly dependent on the presence of added soluble cyclic AMP-dependent protein kinase. Cyclic AMP also stimulated phosphorylation of membrane proteins in sarcolemma, but this phosphorylation was mediated by an endogenous protein kinase activity. The apparent molecular weights of these phosphorylated proteins were 165,000, 90,000, 56,000, 24,000, and 11,000. The results suggest that sarcolemma may contain an integral enzyme complex, not present in sarcoplasmic reticulum, that contains beta-adrenergic receptors, adenylate cyclase, cyclic AMP-dependent protein kinase, and several substrates of the protein kinase."}
{"id": "PMID:216678", "title": "Early effect of progesterone on levels of cyclic adenosine 3':5'-monophosphate in Xenopus oocytes.", "content": "Progesterone treatment of Xenopus oocytes in vitro causes progression through meiotic cell division. The role of altered intracellular levels of cAMP on the initiation of meiotic cell division has been studied. Basal levels of cAMP averaged 1.5 pmol in oocytes from eight females, and exposure to progesterone caused a rapid drop in cAMP to about 40 to 60% of basal. Half-maximal decreases occurred within 15 to 60 s, and cAMP returned to near basal values by 20 min after progesterone. Theophylline inhibition of progesterone-induced cell division was characterized by a small increase in basal levels of cAMP and a reduced drop in cAMP due to the hormone. Cholera toxin, an activator of adenylate cyclase, was found to be a potent inhibitor of progesterone-induced meiosis, with half-maximal inhibition at 8 times 10(-12) M. In addition, the purified A subunit of cholera toxin was an effective inhibitor of progesterone action when microinjected into oocytes, with half-maximal inhibition occurring at an approximate internal concentration of 1 X 10(-7) M. Cholera toxin alone increased cAMP levels by 20%, but upon addition of progesterone, the level increased transiently to 200% of basal, indicating that the inhibition was due to elevated levels of cAMP. The results support a model in which the initiation of meiotic cell division is regulated by cAMP and protein phosphorylation.", "contents": "Early effect of progesterone on levels of cyclic adenosine 3':5'-monophosphate in Xenopus oocytes. Progesterone treatment of Xenopus oocytes in vitro causes progression through meiotic cell division. The role of altered intracellular levels of cAMP on the initiation of meiotic cell division has been studied. Basal levels of cAMP averaged 1.5 pmol in oocytes from eight females, and exposure to progesterone caused a rapid drop in cAMP to about 40 to 60% of basal. Half-maximal decreases occurred within 15 to 60 s, and cAMP returned to near basal values by 20 min after progesterone. Theophylline inhibition of progesterone-induced cell division was characterized by a small increase in basal levels of cAMP and a reduced drop in cAMP due to the hormone. Cholera toxin, an activator of adenylate cyclase, was found to be a potent inhibitor of progesterone-induced meiosis, with half-maximal inhibition at 8 times 10(-12) M. In addition, the purified A subunit of cholera toxin was an effective inhibitor of progesterone action when microinjected into oocytes, with half-maximal inhibition occurring at an approximate internal concentration of 1 X 10(-7) M. Cholera toxin alone increased cAMP levels by 20%, but upon addition of progesterone, the level increased transiently to 200% of basal, indicating that the inhibition was due to elevated levels of cAMP. The results support a model in which the initiation of meiotic cell division is regulated by cAMP and protein phosphorylation."}
{"id": "PMID:216679", "title": "Inhibition of cyclic nucleotide phosphodiesterase during exposure to WI-38 cells to prostaglandin E1.", "content": "Short term incubation of WI-38 cultures with 5.7 micron prostaglandin E1 (PGE1) caused cyclic AMP phosphodiesterase activity in fibroblast homogenates to fall by 25 to 35% as compared to controls. The PGE1-induced decline in phosphodiesterase activity coincided with a rapid increase in intracellular cyclic AMP levels in response to the hormone and was rapidly reversed by washing the cultures free of the prostaglandin before homogenizing the cells. The effect of PGE1 on WI-38 phosphodiesterase activity was localized to the enzyme form(s) present in 27,000 times g supernatant fractions of cell homogenates. These data suggest that the pattern of cyclic AMP accumulation in WI-38 fibroblasts exposed to PGE1 may be related, at least in part, to decreased phosphodiesterase activity during hormone stimulation.", "contents": "Inhibition of cyclic nucleotide phosphodiesterase during exposure to WI-38 cells to prostaglandin E1. Short term incubation of WI-38 cultures with 5.7 micron prostaglandin E1 (PGE1) caused cyclic AMP phosphodiesterase activity in fibroblast homogenates to fall by 25 to 35% as compared to controls. The PGE1-induced decline in phosphodiesterase activity coincided with a rapid increase in intracellular cyclic AMP levels in response to the hormone and was rapidly reversed by washing the cultures free of the prostaglandin before homogenizing the cells. The effect of PGE1 on WI-38 phosphodiesterase activity was localized to the enzyme form(s) present in 27,000 times g supernatant fractions of cell homogenates. These data suggest that the pattern of cyclic AMP accumulation in WI-38 fibroblasts exposed to PGE1 may be related, at least in part, to decreased phosphodiesterase activity during hormone stimulation."}
{"id": "PMID:216681", "title": "Effect of contact inhibition on the regulation of cholesterol metabolism in cultured vascular endothelial cells.", "content": "Cholesterol synthesis in actively growing bovine vascular endothelial cells is regulated by low density lipoprotein (LDL) at a step prior to mevalonate formation, in a manner comparable to that found in aortic smooth muscle cells. LDL uptake by these cells is associated with induction of cholesterol esterification, an increase in total cell cholesterol, and an inhibition of endogenous sterol synthesis. In contrast, cholesterol metabolism in confluent contact-inhibited endothelial cultures was not significantly affected by LDL even though the cells bind the lipoprotein at high affinity receptor sites. Lysosomal degradation and subsequent regulatory effects on cellular cholesterol metabolism, however, were observed in contact-inhibited endothelial cells incubated with cationized rather than native LDL. Cationized LDL enter the cells independently of the high affinity sites. Therefore, the primary regulation of cholesterol metabolism in these cells is neither through the appropriate intracellular enzymes nor through the high affinity surface receptors, but via an inhibition of LDL internalization. It is suggested that this inhibition is due to a strict contact-inhibited morphology which enables the endothelium of the larger arteries to function as a selective barrier to the high circulating levels of plasma LDL.", "contents": "Effect of contact inhibition on the regulation of cholesterol metabolism in cultured vascular endothelial cells. Cholesterol synthesis in actively growing bovine vascular endothelial cells is regulated by low density lipoprotein (LDL) at a step prior to mevalonate formation, in a manner comparable to that found in aortic smooth muscle cells. LDL uptake by these cells is associated with induction of cholesterol esterification, an increase in total cell cholesterol, and an inhibition of endogenous sterol synthesis. In contrast, cholesterol metabolism in confluent contact-inhibited endothelial cultures was not significantly affected by LDL even though the cells bind the lipoprotein at high affinity receptor sites. Lysosomal degradation and subsequent regulatory effects on cellular cholesterol metabolism, however, were observed in contact-inhibited endothelial cells incubated with cationized rather than native LDL. Cationized LDL enter the cells independently of the high affinity sites. Therefore, the primary regulation of cholesterol metabolism in these cells is neither through the appropriate intracellular enzymes nor through the high affinity surface receptors, but via an inhibition of LDL internalization. It is suggested that this inhibition is due to a strict contact-inhibited morphology which enables the endothelium of the larger arteries to function as a selective barrier to the high circulating levels of plasma LDL."}
{"id": "PMID:216684", "title": "The chemistry and biology of thymosin. I. Isolation, characterization, and biological activities of thymosin alpha1 and polypeptide beta1 from calf thymus.", "content": "A partially purified extract from thymus tissue termed thymosin Fraction 5 has been shown to reconstitute immunological deficiencies resulting from the lack of thymic function in several animal models, as well as humans with primary and secondary immunodeficiency diseases. Thymosin Fraction 5 consists of a family of polypeptides with molecular weights ranging from 1,000 to 15,000. Several of these polypeptides contribute individually to the biological activity of the parent compound. Two polypeptide components of thymosin Fraction 5, termed thymosin alpha1 and polypeptide beta1, have been characterized chemically and biologically. Thymosin alpha1 is a highly acidic molecule composed of 28 amino acid residues. This polypeptide has potent biological activity and has been found to be 10 to 1,000 times as active as thymosin Fraction 5 in one in vivo and several in vitro bioassay systems designed to measure differentiation and function of thymus-dependent lymphocytes (T cells). Polypeptide beta1, in contrast, is inactive in our bioassay systems, suggesting that it is not involved in thymic hormone action. Sequence analysis and homology studies have indicated that polypeptide beta1, although present in Fraction 5, does not contribute to the biological activity of thymosin Fraction 5.", "contents": "The chemistry and biology of thymosin. I. Isolation, characterization, and biological activities of thymosin alpha1 and polypeptide beta1 from calf thymus. A partially purified extract from thymus tissue termed thymosin Fraction 5 has been shown to reconstitute immunological deficiencies resulting from the lack of thymic function in several animal models, as well as humans with primary and secondary immunodeficiency diseases. Thymosin Fraction 5 consists of a family of polypeptides with molecular weights ranging from 1,000 to 15,000. Several of these polypeptides contribute individually to the biological activity of the parent compound. Two polypeptide components of thymosin Fraction 5, termed thymosin alpha1 and polypeptide beta1, have been characterized chemically and biologically. Thymosin alpha1 is a highly acidic molecule composed of 28 amino acid residues. This polypeptide has potent biological activity and has been found to be 10 to 1,000 times as active as thymosin Fraction 5 in one in vivo and several in vitro bioassay systems designed to measure differentiation and function of thymus-dependent lymphocytes (T cells). Polypeptide beta1, in contrast, is inactive in our bioassay systems, suggesting that it is not involved in thymic hormone action. Sequence analysis and homology studies have indicated that polypeptide beta1, although present in Fraction 5, does not contribute to the biological activity of thymosin Fraction 5."}
{"id": "PMID:216685", "title": "Suppression of 3-hydroxy-3-methylglutaryl-CoA reductase by low density lipoproteins produced in vitro by lipoprotein lipase action on nonsuppressive very low density lipoproteins.", "content": "Very low density lipoproteins (VLDL), Sf60 to 400, from normolipemic individuals do not suppress 3-hydroxy-3-methylglutaryl-CoA reductase activity in cultured normal human fibroblasts at concentrations 20-fold higher than those of low density lipoproteins (LDL) that give total suppression. To determine if these VLDL contain all of the structural elements necessary for receptor-mediated suppression, they were converted in vitro with bovine milk lipoprotein lipase to low density lipoproteins. These LDL-like lipoproteins were as effective in suppression as LDL isolated directly from plasma, with half-maximal and complete suppression at 1 and 4 microgram of cholesterol ml-1. Neither native LDL nor LDL produced in vitro suppressed receptor-negative fibroblasts. We conclude that action of lipoprotein lipase on VLDL leads to a rearrangement of lipoprotein components that permits interaction of LDL produced in vitro with the LDL-specific cell surface receptor of fibroblasts and subsequent suppression of 3-hydroxy-3-methylglutaryl-CoA reductase.", "contents": "Suppression of 3-hydroxy-3-methylglutaryl-CoA reductase by low density lipoproteins produced in vitro by lipoprotein lipase action on nonsuppressive very low density lipoproteins. Very low density lipoproteins (VLDL), Sf60 to 400, from normolipemic individuals do not suppress 3-hydroxy-3-methylglutaryl-CoA reductase activity in cultured normal human fibroblasts at concentrations 20-fold higher than those of low density lipoproteins (LDL) that give total suppression. To determine if these VLDL contain all of the structural elements necessary for receptor-mediated suppression, they were converted in vitro with bovine milk lipoprotein lipase to low density lipoproteins. These LDL-like lipoproteins were as effective in suppression as LDL isolated directly from plasma, with half-maximal and complete suppression at 1 and 4 microgram of cholesterol ml-1. Neither native LDL nor LDL produced in vitro suppressed receptor-negative fibroblasts. We conclude that action of lipoprotein lipase on VLDL leads to a rearrangement of lipoprotein components that permits interaction of LDL produced in vitro with the LDL-specific cell surface receptor of fibroblasts and subsequent suppression of 3-hydroxy-3-methylglutaryl-CoA reductase."}
{"id": "PMID:216686", "title": "Identification of four major classes of sulfhydryl groups in human blood platelets. Ferricyanide titration of spin-labeled platelets.", "content": "Human blood platelets have been labeled with the sulfhydryl-specific spin labels, 4-iodoacetamido-2,2,6,6-tetramethylpiperidine-1-oxyl and 3-maleimido-2,2,5,5-tetramethylpyrrolidine-1-oxyl. First, the ESR spectra of platelets labeled with either reagent revealed two classes of sulfhydryl groups, a mobile class and an immobile class. Second, when spin-labeled platelets were titrated with high concentrations of potassium ferricyanide (greater than 10(-3) M), there was a decrease in the peak heights of the mobile class of sulfhydryl groups due to dipole-dipole exchange. Third, plots of peak heights of the mobile class versus ferricyanide concentration revealed three classes of mobile sulfhydryl groups compared to a single immobile class. This technique may be used to show the relative locations of spin-labeled groups on cell surfaces.", "contents": "Identification of four major classes of sulfhydryl groups in human blood platelets. Ferricyanide titration of spin-labeled platelets. Human blood platelets have been labeled with the sulfhydryl-specific spin labels, 4-iodoacetamido-2,2,6,6-tetramethylpiperidine-1-oxyl and 3-maleimido-2,2,5,5-tetramethylpyrrolidine-1-oxyl. First, the ESR spectra of platelets labeled with either reagent revealed two classes of sulfhydryl groups, a mobile class and an immobile class. Second, when spin-labeled platelets were titrated with high concentrations of potassium ferricyanide (greater than 10(-3) M), there was a decrease in the peak heights of the mobile class of sulfhydryl groups due to dipole-dipole exchange. Third, plots of peak heights of the mobile class versus ferricyanide concentration revealed three classes of mobile sulfhydryl groups compared to a single immobile class. This technique may be used to show the relative locations of spin-labeled groups on cell surfaces."}
{"id": "PMID:216687", "title": "Coupling of glucagon receptor to adenylyl cyclase. Requirement of a receptor-related guanyl nucleotide binding site for coupling of receptor to the enzyme.", "content": "Effects of glucagon and guanyl nucleotides on the rat liver plasma membrane adenylyl cyclase were studied. It was established that: 1) glucagon stimulates the fully guanyl-5'-yl imidodiphosphate (GMP-P(NH)P)-activated enzyme between 20 and 70%, provided a guanyl nucleotide is present in the assay; 2) glucagon has no effect on adenylyl cyclase activity in membranes activated fully by GMP-P(NH)P and then washed free of nucleotides. It is concluded that occupancy of the guanyl nucleotide binding site that activates the catalytic moiety of the system is not sufficient to promote hormone-receptor coupling to adenylyl cyclase and that occupancy of a second site by guanyl nucleotides is essential to effect stimulation of adenylyl cyclase by the glucagon-receptor complex. The data presented raise the question whether the guanyl nucleotide site that promotes coupling is distinct from the guanyl nucleotide site that modulates binding of glucagon to receptor and whether the occupancy of the guanyl nucleotide site associated with the catalytic moiety is necessary for coupling.", "contents": "Coupling of glucagon receptor to adenylyl cyclase. Requirement of a receptor-related guanyl nucleotide binding site for coupling of receptor to the enzyme. Effects of glucagon and guanyl nucleotides on the rat liver plasma membrane adenylyl cyclase were studied. It was established that: 1) glucagon stimulates the fully guanyl-5'-yl imidodiphosphate (GMP-P(NH)P)-activated enzyme between 20 and 70%, provided a guanyl nucleotide is present in the assay; 2) glucagon has no effect on adenylyl cyclase activity in membranes activated fully by GMP-P(NH)P and then washed free of nucleotides. It is concluded that occupancy of the guanyl nucleotide binding site that activates the catalytic moiety of the system is not sufficient to promote hormone-receptor coupling to adenylyl cyclase and that occupancy of a second site by guanyl nucleotides is essential to effect stimulation of adenylyl cyclase by the glucagon-receptor complex. The data presented raise the question whether the guanyl nucleotide site that promotes coupling is distinct from the guanyl nucleotide site that modulates binding of glucagon to receptor and whether the occupancy of the guanyl nucleotide site associated with the catalytic moiety is necessary for coupling."}
{"id": "PMID:216690", "title": "Identification of the iron-sulfur center of spinach ferredoxin-nitrite reductase as a tetranuclear center, and preliminary EPR studies of mechanism.", "content": "EPR spectroscopic and chemical analyses of spinach nitrite reductase show that the enzyme contains one reducible iron-sulfur center, and one site for binding either cyanide or nitrite, per siroheme. The heme is nearly all in the high spin ferric state in the enzyme as isolated. The extinction coefficient of the enzyme has been revised to E386 = 7.6 X 10(4) cm-1 (M heme)-1. The iron-sulfur center is reduced with difficulty by agents such as reduced methyl viologen (equilibrated with 1 atm of H2 at pH 7.7 in the presence of hydrogenase) or dithionite. Complexation of the enzyme with CO (a known ligand for nitrite reductase heme) markedly increases the reducibility of the iron-sulfur center. New chemical analyses and reinterpretation of previous data show that the enzyme contains 6 mol of iron and 4 mol of acid-labile S2-/mol of siroheme. The EPR spectrum of reduced nitrite reductase in 80% dimethyl sulfoxide establishes clearly that the enzyme contains a tetranuclear iron-sulfur (Fe4S4) center. The ferriheme and Fe4S4 centers are reduced at similar rates (k = 3 to 4 s-1) by dithionite. The dithionite-reduced Fe4S4 center is rapidly (k = 100 s-1) reoxidized by nitrite. These results indicate a role for the Fe4S4 center in catalysis.", "contents": "Identification of the iron-sulfur center of spinach ferredoxin-nitrite reductase as a tetranuclear center, and preliminary EPR studies of mechanism. EPR spectroscopic and chemical analyses of spinach nitrite reductase show that the enzyme contains one reducible iron-sulfur center, and one site for binding either cyanide or nitrite, per siroheme. The heme is nearly all in the high spin ferric state in the enzyme as isolated. The extinction coefficient of the enzyme has been revised to E386 = 7.6 X 10(4) cm-1 (M heme)-1. The iron-sulfur center is reduced with difficulty by agents such as reduced methyl viologen (equilibrated with 1 atm of H2 at pH 7.7 in the presence of hydrogenase) or dithionite. Complexation of the enzyme with CO (a known ligand for nitrite reductase heme) markedly increases the reducibility of the iron-sulfur center. New chemical analyses and reinterpretation of previous data show that the enzyme contains 6 mol of iron and 4 mol of acid-labile S2-/mol of siroheme. The EPR spectrum of reduced nitrite reductase in 80% dimethyl sulfoxide establishes clearly that the enzyme contains a tetranuclear iron-sulfur (Fe4S4) center. The ferriheme and Fe4S4 centers are reduced at similar rates (k = 3 to 4 s-1) by dithionite. The dithionite-reduced Fe4S4 center is rapidly (k = 100 s-1) reoxidized by nitrite. These results indicate a role for the Fe4S4 center in catalysis."}
{"id": "PMID:216693", "title": "Biogenesis of the cytochrome bc1 complex of yeast mitochondria. A precursor form of the cytoplasmically made subunit V.", "content": "The cytoplasmically made subunit V of the yeast mitochondrial cytochrome bc1 complex is synthesized as a larger polypeptide in vitro. This was shown by programming a reticulocyte lysate with yeast RNA and immunoprecipitating the labeled translation products with a subunit V-specific antiserum. The larger form of subunit V could also be detected in pulse-labeled spheroplasts; upon a subsequent chase, most of it disappeared. A proteolytic fingerprint of the larger form was closely similar to that of the mature subunit. These data suggest that the cytoplasmically made subunit V is translated as a larger precursor which is cleaved to the mature subunit either during or after its entry into the mitochondria.", "contents": "Biogenesis of the cytochrome bc1 complex of yeast mitochondria. A precursor form of the cytoplasmically made subunit V. The cytoplasmically made subunit V of the yeast mitochondrial cytochrome bc1 complex is synthesized as a larger polypeptide in vitro. This was shown by programming a reticulocyte lysate with yeast RNA and immunoprecipitating the labeled translation products with a subunit V-specific antiserum. The larger form of subunit V could also be detected in pulse-labeled spheroplasts; upon a subsequent chase, most of it disappeared. A proteolytic fingerprint of the larger form was closely similar to that of the mature subunit. These data suggest that the cytoplasmically made subunit V is translated as a larger precursor which is cleaved to the mature subunit either during or after its entry into the mitochondria."}
{"id": "PMID:216695", "title": "Creatine phosphate inhibition of adenylate deaminase is mainly due to pyrophosphate.", "content": "Inhibition of rat skeletal muscle adenylate deaminase by creatine phosphate reported previously is due to inorganic pyrophosphate present as a contaminant in commercial preparations of creatine phosphate. This conclusion is based on the following evidence: a compound that inhibits adenylate deaminase can be separated from commercially prepared creatine phosphate by ion exchange chromatography; the inhibition by \"creatine phosphate\" and by the separated inhibitory compound is relieved by treatment with inorganic pyrophosphatase; inhibition by inorganic pyrophosphate is similar to that produced by unpurified creatine phosphate; and pyrophosphate is present in commercially available creatine phosphate in amounts sufficient to account for the inhibition. Some commercial preparations of creatine phosphate contain much less pyrophosphate than others; these preparations are only weakly inhibitory. Inorganic triphosphate is a more powerful inhibitor of the enzyme than pyrophosphate; it may also be present as a contaminant in creatine phosphate.", "contents": "Creatine phosphate inhibition of adenylate deaminase is mainly due to pyrophosphate. Inhibition of rat skeletal muscle adenylate deaminase by creatine phosphate reported previously is due to inorganic pyrophosphate present as a contaminant in commercial preparations of creatine phosphate. This conclusion is based on the following evidence: a compound that inhibits adenylate deaminase can be separated from commercially prepared creatine phosphate by ion exchange chromatography; the inhibition by \"creatine phosphate\" and by the separated inhibitory compound is relieved by treatment with inorganic pyrophosphatase; inhibition by inorganic pyrophosphate is similar to that produced by unpurified creatine phosphate; and pyrophosphate is present in commercially available creatine phosphate in amounts sufficient to account for the inhibition. Some commercial preparations of creatine phosphate contain much less pyrophosphate than others; these preparations are only weakly inhibitory. Inorganic triphosphate is a more powerful inhibitor of the enzyme than pyrophosphate; it may also be present as a contaminant in creatine phosphate."}
{"id": "PMID:216697", "title": "Cyclic AMP-stimulated protein kinases at brain synaptic junctions.", "content": "We have examined endogenous cyclic AMP-stimulated phosphorylation of subcellular fractions of rat brain enriched in synaptic plasma membranes (SPM), purified synaptic junctions (SJ), and postsynaptic densities (PSD). The analyses of these fractions are essential to provide direct evidence for cyclic AMP-dependent endogenous phosphorylation at discrete synaptic junctional loci. Protein kinase activity was measured in subcellular fractions using both endogenous and exogenous (histones) proteins as substrates. The SJ fraction possessed the highest kinase activity toward endogenous protein substrates, 5-fold greater than SPM and approximately 120-fold greater than PSD fractions. Although the kinase activity as measured with histones as substrates was only slightly higher in SJ than SPM fractions, there was a marked preference of kinase activity toward endogenous compared to exogenous substrates in SJ fractions but in SPM fractions. Although overall phosphorylation in SJ fractions was increased only 36% by 5 micron cyclic AMP, there were discrete proteins of Mr = 85,000, 82,000, 78,000, and 55,000 which incorporated 2- to 3-fold more radioactive phosphate in the presence of cyclic AMP. Most, if not all, of the cyclic AMP-independent kinase activity is probably catalyzed by catalytic subunit derived from cyclic AMP-dependent kinase, since the phosphorylation of both exogenous and endogenous proteins was greatly decreased in the presence of a heat-stable inhibitor protein prepared from the soluble fraction of rat brain. The specific retention of SJ protein kinase(s) activity during purification and their resistance to detergent solubilization was achieved by chemical treatments which produce interprotein cross-linking via disulfide bridges. Two SJ polypeptides of Mr = 55,000 and 49,000 were photoaffinity-labeled with [32P]8-N3-cyclic AMP and probably represent the regulatory subunits of the type I and II cyclic AMP-dependent protein kinases. The protein of Mr = 55,000 was phosphorylated in a cyclic AMP-stimulated manner suggesting autophosphorylation as previously observed in other systems.", "contents": "Cyclic AMP-stimulated protein kinases at brain synaptic junctions. We have examined endogenous cyclic AMP-stimulated phosphorylation of subcellular fractions of rat brain enriched in synaptic plasma membranes (SPM), purified synaptic junctions (SJ), and postsynaptic densities (PSD). The analyses of these fractions are essential to provide direct evidence for cyclic AMP-dependent endogenous phosphorylation at discrete synaptic junctional loci. Protein kinase activity was measured in subcellular fractions using both endogenous and exogenous (histones) proteins as substrates. The SJ fraction possessed the highest kinase activity toward endogenous protein substrates, 5-fold greater than SPM and approximately 120-fold greater than PSD fractions. Although the kinase activity as measured with histones as substrates was only slightly higher in SJ than SPM fractions, there was a marked preference of kinase activity toward endogenous compared to exogenous substrates in SJ fractions but in SPM fractions. Although overall phosphorylation in SJ fractions was increased only 36% by 5 micron cyclic AMP, there were discrete proteins of Mr = 85,000, 82,000, 78,000, and 55,000 which incorporated 2- to 3-fold more radioactive phosphate in the presence of cyclic AMP. Most, if not all, of the cyclic AMP-independent kinase activity is probably catalyzed by catalytic subunit derived from cyclic AMP-dependent kinase, since the phosphorylation of both exogenous and endogenous proteins was greatly decreased in the presence of a heat-stable inhibitor protein prepared from the soluble fraction of rat brain. The specific retention of SJ protein kinase(s) activity during purification and their resistance to detergent solubilization was achieved by chemical treatments which produce interprotein cross-linking via disulfide bridges. Two SJ polypeptides of Mr = 55,000 and 49,000 were photoaffinity-labeled with [32P]8-N3-cyclic AMP and probably represent the regulatory subunits of the type I and II cyclic AMP-dependent protein kinases. The protein of Mr = 55,000 was phosphorylated in a cyclic AMP-stimulated manner suggesting autophosphorylation as previously observed in other systems."}
{"id": "PMID:216698", "title": "Purification and characterization of cytochrome c oxidase from rat liver mitochondria.", "content": "Cytochrome c oxidase has been purified from rat liver mitochondria using affinity chromatography. The preparation contains 10.5 to 13.4 nmol of heme a + a3 per mg of protein and migrates as a single band during polyacrylamide gel electrophoresis under nondissociating conditions. It has a heme a/a3 ratio of 1.12 and is free of cytochromes b, c, and c1 as well as the enzymes, NADH dehydrogenase, succinic dehydrogenase, coenzyme Q-cytochrome c reductase, and ATPase. The enzyme preparation consists of six polypeptides having apparent Mr of 66,000, 39,000, 23,000, 14,000, 12,500 and 10,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The peptide composition is similar to those found for cytochrome c oxidases from other systems. The enzymatic activity of the purified enzyme is completely inhibited by carbon monoxide or cyanide, partially inhibited by Triton X-100 and dramatically enhanced by Tween 80 or phospholipids.", "contents": "Purification and characterization of cytochrome c oxidase from rat liver mitochondria. Cytochrome c oxidase has been purified from rat liver mitochondria using affinity chromatography. The preparation contains 10.5 to 13.4 nmol of heme a + a3 per mg of protein and migrates as a single band during polyacrylamide gel electrophoresis under nondissociating conditions. It has a heme a/a3 ratio of 1.12 and is free of cytochromes b, c, and c1 as well as the enzymes, NADH dehydrogenase, succinic dehydrogenase, coenzyme Q-cytochrome c reductase, and ATPase. The enzyme preparation consists of six polypeptides having apparent Mr of 66,000, 39,000, 23,000, 14,000, 12,500 and 10,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The peptide composition is similar to those found for cytochrome c oxidases from other systems. The enzymatic activity of the purified enzyme is completely inhibited by carbon monoxide or cyanide, partially inhibited by Triton X-100 and dramatically enhanced by Tween 80 or phospholipids."}
{"id": "PMID:216699", "title": "Biosynthesis of cytochrome c oxidase by isolated rat liver mitochondria.", "content": "When isolated mitochondria which have been labeled with [3H]leucine are solubilized and treated with anti-serum specific for cytochrome c oxidase, labeled polypeptides which correspond to the three largest polypeptides of this enzyme are immunoprecipitated. This indicates that the three largest polypeptides of cytochrome c oxidase which have Mr of 66,000, 39,000, and 23,000 are synthesized by isolated mitochondria whereas the three smallest ones which have Mr of 14,000, 12,500, and 10,000 are not. The smallest polypeptides are probably synthesized on cytoplasmic ribosomes as has been demonstrated in other systems by in vivo studies. These results are the first demonstration that isolated mammalian mitochondria are capable of synthesizing some of their own polypeptide components. The antiserum used in this study was prepared to highly purified cytochrome c oxidase (12.4 nmol of heme a + a3/mg of protein) from rat liver mitochondria. This antiserum gives a single precipitin line when tested by the Ouchterlony double diffusion technique. Its specificity has been demonstrated by the fact that it: 1) only precipitates heme a + a3, not hemes b, c, or c1, when added to solubilized mitochondria, 2) inhibits cytochrome c oxidase activity at least 85%, and 3) precipitates only those polypeptides found in purified cytochrome c oxidase when added to solubilized mitochondria labeled in vivo.", "contents": "Biosynthesis of cytochrome c oxidase by isolated rat liver mitochondria. When isolated mitochondria which have been labeled with [3H]leucine are solubilized and treated with anti-serum specific for cytochrome c oxidase, labeled polypeptides which correspond to the three largest polypeptides of this enzyme are immunoprecipitated. This indicates that the three largest polypeptides of cytochrome c oxidase which have Mr of 66,000, 39,000, and 23,000 are synthesized by isolated mitochondria whereas the three smallest ones which have Mr of 14,000, 12,500, and 10,000 are not. The smallest polypeptides are probably synthesized on cytoplasmic ribosomes as has been demonstrated in other systems by in vivo studies. These results are the first demonstration that isolated mammalian mitochondria are capable of synthesizing some of their own polypeptide components. The antiserum used in this study was prepared to highly purified cytochrome c oxidase (12.4 nmol of heme a + a3/mg of protein) from rat liver mitochondria. This antiserum gives a single precipitin line when tested by the Ouchterlony double diffusion technique. Its specificity has been demonstrated by the fact that it: 1) only precipitates heme a + a3, not hemes b, c, or c1, when added to solubilized mitochondria, 2) inhibits cytochrome c oxidase activity at least 85%, and 3) precipitates only those polypeptides found in purified cytochrome c oxidase when added to solubilized mitochondria labeled in vivo."}
{"id": "PMID:216701", "title": "Characterization of the apolipoprotein B polypeptide of human plasma low density lipoprotein in detergent and denaturation solutions.", "content": "Apolipoprotein B, the polypeptide moiety of human serum low density lipoprotein, is subject to degradation (as evidenced by sodium dodecyl sulfate-polyacrylamide gel electrophoresis) both in the intact particle and after delipidation. Protease inhibitors, sodium azide, and nitrogen saturation did not influence the rate or degree of degradation. Lipid-free apolipoprotein B prepared by gel exclusion chromatography in sodium dodecyl sulfate bound a limited number of detergent molecules (up to 300) in monomeric sodium dodecyl sulfate solutions; circular dichroic spectra of this complex were similar to spectra of the intact lipoprotein. Near the critical micelle concentrations, a large, cooperative increase in detergent binding occurred, accompanied by circular dichroic changes indicating increased alpha helicity. By sucrose density centrifugation, lysopalmitoyl phosphatidylcholine could be substituted for the anionic detergent; about 300 mol of lysolipid were bound to the polypeptide. Replacement of detergent with guanidine hydrochloride by dialysis produced a soluble polypeptide with no ordered structure at denaturant concentrations above 7 M. At lower guanidine hydrochloride concentrations, structural elements were regained in a broad, reversible transition. It appears that apolipoprotein B is an easily degraded polypeptide with regions resembling water-soluble proteins but other regions which interact with lipid (or synthetic amphiphiles) and produce an overall insolubility in aqueous solution in the absence of amphiphilic ligands.", "contents": "Characterization of the apolipoprotein B polypeptide of human plasma low density lipoprotein in detergent and denaturation solutions. Apolipoprotein B, the polypeptide moiety of human serum low density lipoprotein, is subject to degradation (as evidenced by sodium dodecyl sulfate-polyacrylamide gel electrophoresis) both in the intact particle and after delipidation. Protease inhibitors, sodium azide, and nitrogen saturation did not influence the rate or degree of degradation. Lipid-free apolipoprotein B prepared by gel exclusion chromatography in sodium dodecyl sulfate bound a limited number of detergent molecules (up to 300) in monomeric sodium dodecyl sulfate solutions; circular dichroic spectra of this complex were similar to spectra of the intact lipoprotein. Near the critical micelle concentrations, a large, cooperative increase in detergent binding occurred, accompanied by circular dichroic changes indicating increased alpha helicity. By sucrose density centrifugation, lysopalmitoyl phosphatidylcholine could be substituted for the anionic detergent; about 300 mol of lysolipid were bound to the polypeptide. Replacement of detergent with guanidine hydrochloride by dialysis produced a soluble polypeptide with no ordered structure at denaturant concentrations above 7 M. At lower guanidine hydrochloride concentrations, structural elements were regained in a broad, reversible transition. It appears that apolipoprotein B is an easily degraded polypeptide with regions resembling water-soluble proteins but other regions which interact with lipid (or synthetic amphiphiles) and produce an overall insolubility in aqueous solution in the absence of amphiphilic ligands."}
{"id": "PMID:216702", "title": "Molecular weight and hydrodynamic properties of apolipoprotein B in guanidine hydrochloride and sodium dodecyl sulfate solutions.", "content": "The apolipoprotein B polypeptide of human serum low density lipoprotein exists (after reduction of disulfide bonds) as a random coil with a molecular weight of 250,000 in concentrated solutions of guanidine hydrochloride. With intact disulfide bonds, there is a limited restraint on the polypeptide conformation in this denaturing solvent. In the presence of saturating amounts of bound sodium dodecyl sulfate, the apolipoprotein is dimeric and highly asymmetric. This work substantiates the monomeric molecular weight of 250,000 for apolipoprotein B reported by others (Smith, R., Dawson, J.R., and Tanford, C. (1972) J. Biol. Chem. 247, 3376-3381) and demonstrates that the dimeric state of the polypeptide extant in vivo is maintained in micellar detergent solution.", "contents": "Molecular weight and hydrodynamic properties of apolipoprotein B in guanidine hydrochloride and sodium dodecyl sulfate solutions. The apolipoprotein B polypeptide of human serum low density lipoprotein exists (after reduction of disulfide bonds) as a random coil with a molecular weight of 250,000 in concentrated solutions of guanidine hydrochloride. With intact disulfide bonds, there is a limited restraint on the polypeptide conformation in this denaturing solvent. In the presence of saturating amounts of bound sodium dodecyl sulfate, the apolipoprotein is dimeric and highly asymmetric. This work substantiates the monomeric molecular weight of 250,000 for apolipoprotein B reported by others (Smith, R., Dawson, J.R., and Tanford, C. (1972) J. Biol. Chem. 247, 3376-3381) and demonstrates that the dimeric state of the polypeptide extant in vivo is maintained in micellar detergent solution."}
{"id": "PMID:216704", "title": "Properties of protein kinase and adenylate cyclase-deficient variants of a macrophage-like cell line.", "content": "Stable variants of the macrophage-like cell line J774.2, defective in adenylate cyclase and protein kinase activities, were selected by cloning cells resistant to the growth-inhibitory effect of cholera toxin and 8-bromo-adenosine 3':5' cyclic monophosphoric acid (8 Br-cAMP), respectively. These variants were analyzed for their ability to respond to cyclic AMP-mediated enhancement of phagocytosis and cyclic AMP-mediated inhibition of plasminogen activator secretion and growtn. The adenylate cyclase variants were unaffected by cholera toxin but were sensitive to 8 Br-cAMP-mediated inhibition of plasminogen activator secretion and growth. One of these variants exhibited a defect in phagocytosis that could be corrected by 8 Br-cAMP. The protein kinase variants exhibited normal basal phagocytosis that could not be stimulated by either 8 Br-cAMP or cholera toxin; they were also insensitive to cyclic AMP-mediated inhibition of plasminogen activator secretion and growth. The studies demonstrate that the three effects of cyclic AMP in J774.2--inhibition of growth and plasminogen activator secretion, and enhancement of basal Fc-mediated phagocytosis--are mediated by a cyclic AMP-dependent portein kinase. The results support the usefulness of variants in cyclic nucleotide metabolism in understanding the regulation of differentiated cell function by cyclic AMP.", "contents": "Properties of protein kinase and adenylate cyclase-deficient variants of a macrophage-like cell line. Stable variants of the macrophage-like cell line J774.2, defective in adenylate cyclase and protein kinase activities, were selected by cloning cells resistant to the growth-inhibitory effect of cholera toxin and 8-bromo-adenosine 3':5' cyclic monophosphoric acid (8 Br-cAMP), respectively. These variants were analyzed for their ability to respond to cyclic AMP-mediated enhancement of phagocytosis and cyclic AMP-mediated inhibition of plasminogen activator secretion and growtn. The adenylate cyclase variants were unaffected by cholera toxin but were sensitive to 8 Br-cAMP-mediated inhibition of plasminogen activator secretion and growth. One of these variants exhibited a defect in phagocytosis that could be corrected by 8 Br-cAMP. The protein kinase variants exhibited normal basal phagocytosis that could not be stimulated by either 8 Br-cAMP or cholera toxin; they were also insensitive to cyclic AMP-mediated inhibition of plasminogen activator secretion and growth. The studies demonstrate that the three effects of cyclic AMP in J774.2--inhibition of growth and plasminogen activator secretion, and enhancement of basal Fc-mediated phagocytosis--are mediated by a cyclic AMP-dependent portein kinase. The results support the usefulness of variants in cyclic nucleotide metabolism in understanding the regulation of differentiated cell function by cyclic AMP."}
{"id": "PMID:216705", "title": "Coordinate control of Balb/c3T3 cell survival and multiplication by serum or calcium pyrophosphate complexes.", "content": "Balb/c3T3 cells in crowded cultures detach from the dish when deprived of serum, and the survivors incorporate 3H-thymidine at a reduced rate. The detachment becomes pronounced two hours after removal of serum, and reaches its maximum rate between two and four hours. Cells in sparse culture are not detached by serum removal, and their rate of 3H-thymidine incorporation is only slightly reduced. As the sparse cultures grow into more crowded cultures, and the serum is depleted, increasing numbers detach. The detached cells are incapable of reattaching when placed in a new dish with ample fresh serum. The cells are leaky to cellular constituents and appear to be dead. Detachment is a consequence rather than the cause of cell death, and can be produced by agents which inhibit cellular energy metabolism. The cells on the dish which survive serum deprivation are fully viable and grow rapidly when serum is added. When they become crowded they are as sensitive to serum deprivation as was the original population. They are therefore not selected for a low serum requirement but apparently survive because they spread into the space vacated by the detaching cells and then behave as sparse cultures in response to serum variations. Insoluble complexes of Ca2+ and pyrophosphate (Ca2+-PPi) show the same concentration dependence in promoting cell survival as in stimulating 3H-thymidine incorporation, showing that a single substance can be responsible for both activities. It is concluded that survival and growth are part of the coordinate response of 3T3 cells to single external effectors. The results are discussed in terms of a simple model in which the coordinate response is regulated by the availability of Mg2+ for transphosphorylation reactions within the cell, and the availability depends on the binding affinity of cellular membranes for Mg2+. The difference between survival and multiplication is postulated to be in the intensity and duration rather than the kind of stimulus.", "contents": "Coordinate control of Balb/c3T3 cell survival and multiplication by serum or calcium pyrophosphate complexes. Balb/c3T3 cells in crowded cultures detach from the dish when deprived of serum, and the survivors incorporate 3H-thymidine at a reduced rate. The detachment becomes pronounced two hours after removal of serum, and reaches its maximum rate between two and four hours. Cells in sparse culture are not detached by serum removal, and their rate of 3H-thymidine incorporation is only slightly reduced. As the sparse cultures grow into more crowded cultures, and the serum is depleted, increasing numbers detach. The detached cells are incapable of reattaching when placed in a new dish with ample fresh serum. The cells are leaky to cellular constituents and appear to be dead. Detachment is a consequence rather than the cause of cell death, and can be produced by agents which inhibit cellular energy metabolism. The cells on the dish which survive serum deprivation are fully viable and grow rapidly when serum is added. When they become crowded they are as sensitive to serum deprivation as was the original population. They are therefore not selected for a low serum requirement but apparently survive because they spread into the space vacated by the detaching cells and then behave as sparse cultures in response to serum variations. Insoluble complexes of Ca2+ and pyrophosphate (Ca2+-PPi) show the same concentration dependence in promoting cell survival as in stimulating 3H-thymidine incorporation, showing that a single substance can be responsible for both activities. It is concluded that survival and growth are part of the coordinate response of 3T3 cells to single external effectors. The results are discussed in terms of a simple model in which the coordinate response is regulated by the availability of Mg2+ for transphosphorylation reactions within the cell, and the availability depends on the binding affinity of cellular membranes for Mg2+. The difference between survival and multiplication is postulated to be in the intensity and duration rather than the kind of stimulus."}
{"id": "PMID:216706", "title": "Determination of 6-methyladenine in DNA by high-performance liquid chromatography.", "content": "A method for the determination of 6-methyladenine (6MA) by high-performance liquid chromatography (HPLC) has been developed. DNA bases were separated by using the strong cation-exchange resin Zipax SCX. Purine bases were obtained by hydrolysis and dialysis of DNA and analysed by HPLC. 6MA in DNA from Escherichia coli was determined by the proposed method. It is suggested that the method could be applicable to analyses of 6MA from other biological sources.", "contents": "Determination of 6-methyladenine in DNA by high-performance liquid chromatography. A method for the determination of 6-methyladenine (6MA) by high-performance liquid chromatography (HPLC) has been developed. DNA bases were separated by using the strong cation-exchange resin Zipax SCX. Purine bases were obtained by hydrolysis and dialysis of DNA and analysed by HPLC. 6MA in DNA from Escherichia coli was determined by the proposed method. It is suggested that the method could be applicable to analyses of 6MA from other biological sources."}
{"id": "PMID:216707", "title": "Subcellular localization of the superoxide-forming enzyme in human neutrophils.", "content": "The subcellular distribution of the superoxide (O2-)-forming enzyme in human neutrophils was investigated. Cells were activated by phorbolmyristate acetate or by opsonized zymosan, and were then fractionated by zonal-rate sedimentation at two different speeds. At high speed, the specific granules were resolved from the azurophils and the membrane fraction, while at low speed, the azurophil granules could be separated from fast-sedimenting particle aggregates. Under both conditions, the major portion of the O-2--forming activity (60--70% of the total) was found to be associated with the membrane fraction which was characterized by the presence of alkaline phosphatase, alkaline phosphodiesterase I, and acid aryl phosphatase. No significant O-2--forming activity was found in either specific or azurophil granules. Some activity was present in the fastest sedimenting fractions which, as shown by electron microscopy, were heterogeneous and contained aggregated material which included membrane fragments. These fractionation results provide strong additional support for the current view that the activable O-2--forming system is localized in the plasma membrane of human neutrophils.", "contents": "Subcellular localization of the superoxide-forming enzyme in human neutrophils. The subcellular distribution of the superoxide (O2-)-forming enzyme in human neutrophils was investigated. Cells were activated by phorbolmyristate acetate or by opsonized zymosan, and were then fractionated by zonal-rate sedimentation at two different speeds. At high speed, the specific granules were resolved from the azurophils and the membrane fraction, while at low speed, the azurophil granules could be separated from fast-sedimenting particle aggregates. Under both conditions, the major portion of the O-2--forming activity (60--70% of the total) was found to be associated with the membrane fraction which was characterized by the presence of alkaline phosphatase, alkaline phosphodiesterase I, and acid aryl phosphatase. No significant O-2--forming activity was found in either specific or azurophil granules. Some activity was present in the fastest sedimenting fractions which, as shown by electron microscopy, were heterogeneous and contained aggregated material which included membrane fragments. These fractionation results provide strong additional support for the current view that the activable O-2--forming system is localized in the plasma membrane of human neutrophils."}
{"id": "PMID:216708", "title": "An ascorbate-mediated transmembrane-reducing system of the human erythrocyte.", "content": "Actively metabolizing human erythrocytes catalyze the extracellular reduction of ferricyanide to ferrocyanide. Because neither of these anions can enter the cell, reducing equivalents generated in the course of glycolysis must in some manner be transferred across the cell membrane, thereby resulting in ferricyanide reduction. Work described in this paper suggests that the transmembrane reduction is effected by ascorbic acid. This compound in its oxidized form (dehydroascorbate) rapidly enters the cell. Here it obtains reducing equivalents which appear to come from NADH made available at the level of glyceraldehyde 3-phosphate dehydrogenase. Once reduced, it leaves the cell as ascorbic acid and accomplishes the non-enzymatic reduction of ferricyanide.", "contents": "An ascorbate-mediated transmembrane-reducing system of the human erythrocyte. Actively metabolizing human erythrocytes catalyze the extracellular reduction of ferricyanide to ferrocyanide. Because neither of these anions can enter the cell, reducing equivalents generated in the course of glycolysis must in some manner be transferred across the cell membrane, thereby resulting in ferricyanide reduction. Work described in this paper suggests that the transmembrane reduction is effected by ascorbic acid. This compound in its oxidized form (dehydroascorbate) rapidly enters the cell. Here it obtains reducing equivalents which appear to come from NADH made available at the level of glyceraldehyde 3-phosphate dehydrogenase. Once reduced, it leaves the cell as ascorbic acid and accomplishes the non-enzymatic reduction of ferricyanide."}
{"id": "PMID:216709", "title": "Role of microtubules in low density lipoprotein processing by cultured cells.", "content": "The effect of the microtubule inhibitor colchicine on the metabolism of (125)I-low density lipoprotein (LDL) by cultured human skin fibroblasts and aortic medial cells was studied in vitro. Colchicine did not alter the binding of LDL to cell surface receptors. However, the rate of LDL endocytosis was reduced to 58% of that expected. Despite diminished endocytosis, LDL was found to accumulate within the cells to 165% of that expected, whereas the release of LDL protein degradation products into the medium was reduced to 34% of control, findings consistent with a reduced rate of intracellular LDL breakdown. Colchicine did not alter cell content of the acid protease which degrades LDL, nor did [(3)H]colchicine accumulate in lysosomal fractions. However, colchicine did alter the intracellular distribution of both fibroblast lysosomes and endosomes. After colchicine, lysosomes tended to accumulate in the perinuclear region, whereas endosomes were found at the cell periphery. These findings are consistent with the hypothesis that ingested LDL is less available to lysosomal enzymes in the presence of colchicine. The actions of colchicine appear to be a result of destruction of cell microtubules. Lumicolchicine, a mixture of colchicine isomers which (unlike the parent compound) does not bind to the subunit of microtubules, was without effect. The uptake and degradation of LDL by cultured cells consists of both a receptor-specific component and nonspecific pinocytosis. Important differences must exist between these processes because even large amounts of LDL taken up and degraded by the nonspecific route fail to regulate key aspects of intracellular cholesterol metabolism. Colchicine selectively inhibited receptor-mediated LDL degradation. No effect was demonstrable on the nonspecific degradation of LDL by familial hypercholesterolemia fibroblasts grown in medium containing serum and added sterols. The degradation of bovine albumin by normal cells was also unaffected. Colchicine sensitivity appears to be a biochemical marker for the LDL receptor-specific metabolic pathway. Cytochalasins inhibit crosslinking and polymerization of cell microfilaments (although other important cell effects also occur). Cytochalasin D reduced LDL degradation to 44% of that expected. This result and the actions of colchicine suggest that cytoskeletal components such as microtubules and possibly microfilaments facilitate normal LDL metabolism.", "contents": "Role of microtubules in low density lipoprotein processing by cultured cells. The effect of the microtubule inhibitor colchicine on the metabolism of (125)I-low density lipoprotein (LDL) by cultured human skin fibroblasts and aortic medial cells was studied in vitro. Colchicine did not alter the binding of LDL to cell surface receptors. However, the rate of LDL endocytosis was reduced to 58% of that expected. Despite diminished endocytosis, LDL was found to accumulate within the cells to 165% of that expected, whereas the release of LDL protein degradation products into the medium was reduced to 34% of control, findings consistent with a reduced rate of intracellular LDL breakdown. Colchicine did not alter cell content of the acid protease which degrades LDL, nor did [(3)H]colchicine accumulate in lysosomal fractions. However, colchicine did alter the intracellular distribution of both fibroblast lysosomes and endosomes. After colchicine, lysosomes tended to accumulate in the perinuclear region, whereas endosomes were found at the cell periphery. These findings are consistent with the hypothesis that ingested LDL is less available to lysosomal enzymes in the presence of colchicine. The actions of colchicine appear to be a result of destruction of cell microtubules. Lumicolchicine, a mixture of colchicine isomers which (unlike the parent compound) does not bind to the subunit of microtubules, was without effect. The uptake and degradation of LDL by cultured cells consists of both a receptor-specific component and nonspecific pinocytosis. Important differences must exist between these processes because even large amounts of LDL taken up and degraded by the nonspecific route fail to regulate key aspects of intracellular cholesterol metabolism. Colchicine selectively inhibited receptor-mediated LDL degradation. No effect was demonstrable on the nonspecific degradation of LDL by familial hypercholesterolemia fibroblasts grown in medium containing serum and added sterols. The degradation of bovine albumin by normal cells was also unaffected. Colchicine sensitivity appears to be a biochemical marker for the LDL receptor-specific metabolic pathway. Cytochalasins inhibit crosslinking and polymerization of cell microfilaments (although other important cell effects also occur). Cytochalasin D reduced LDL degradation to 44% of that expected. This result and the actions of colchicine suggest that cytoskeletal components such as microtubules and possibly microfilaments facilitate normal LDL metabolism."}
{"id": "PMID:216712", "title": "Chemical determinants of enamel hypoplasia in children with disorders of calcium and phosphate homeostasis.", "content": "Studies of children with disorders of calcium and phosphate homeostasis indicate that hypocalcaemia, but not hypophosphataemia, is a significant and specific factor in the etiology of enamel hypoplasia. Only those teeth were affected that had developed during the hypocalcaemic episodes.", "contents": "Chemical determinants of enamel hypoplasia in children with disorders of calcium and phosphate homeostasis. Studies of children with disorders of calcium and phosphate homeostasis indicate that hypocalcaemia, but not hypophosphataemia, is a significant and specific factor in the etiology of enamel hypoplasia. Only those teeth were affected that had developed during the hypocalcaemic episodes."}
{"id": "PMID:216713", "title": "Enamel matrix proteins in normal and abnormal amelogenesis.", "content": "Histochemical techniques have been used to study three stages of enamel maturation in normal (fetal calf, newborn human, adult human) and abnormal amelogenesis (odontodysplasia, fluorosis, a compound-complex odontome, and an invaginated odontome). The amount of Type I matrix secreted decreases as amelogenesis progresses. Pockets of Type II matrix may be left at the dentino-enamel junction after maturation of enamel to Type III. Fluorosed enamel contains pockets which may extend the width of the enamel. All stages of enamel maturation may be seen in the compound-complex odontoma.", "contents": "Enamel matrix proteins in normal and abnormal amelogenesis. Histochemical techniques have been used to study three stages of enamel maturation in normal (fetal calf, newborn human, adult human) and abnormal amelogenesis (odontodysplasia, fluorosis, a compound-complex odontome, and an invaginated odontome). The amount of Type I matrix secreted decreases as amelogenesis progresses. Pockets of Type II matrix may be left at the dentino-enamel junction after maturation of enamel to Type III. Fluorosed enamel contains pockets which may extend the width of the enamel. All stages of enamel maturation may be seen in the compound-complex odontoma."}
{"id": "PMID:216743", "title": "Microbiological aspects of polyphosphate injection in the processing and chill storage of poultry.", "content": "During commercial processing of broiler chickens, injection of polyphosphate (Puron 604 or 6040) resulted in microorganisms being added to the deep breast muscle. The level of contamination was related to the microbiological condition of the injection solution. Injection of polyphosphate had no effect on the shelf-life of fresh chilled carcasses held at 1 degree of 10 degrees C but changes were observed in the growth rate of microorganisms in the deep muscle and in the composition of the muscle microflora following storage. Cross-contamination of carcasses and the transfer of organisms from the skin to the deep muscle during injection was demonstrated with a marker strain of Clostridium perfringens. However, both processes were influenced by the number of marker organisms applied initially to the skin. The above findings are discussed in relation to the possible behaviour of any food poisoning bacteria present.", "contents": "Microbiological aspects of polyphosphate injection in the processing and chill storage of poultry. During commercial processing of broiler chickens, injection of polyphosphate (Puron 604 or 6040) resulted in microorganisms being added to the deep breast muscle. The level of contamination was related to the microbiological condition of the injection solution. Injection of polyphosphate had no effect on the shelf-life of fresh chilled carcasses held at 1 degree of 10 degrees C but changes were observed in the growth rate of microorganisms in the deep muscle and in the composition of the muscle microflora following storage. Cross-contamination of carcasses and the transfer of organisms from the skin to the deep muscle during injection was demonstrated with a marker strain of Clostridium perfringens. However, both processes were influenced by the number of marker organisms applied initially to the skin. The above findings are discussed in relation to the possible behaviour of any food poisoning bacteria present."}
{"id": "PMID:216744", "title": "Immune response to virus-infection-associated (VIA) antigen in cattle repeatedly vaccinated with foot-and-mouth disease virus inactivated by formalin or acetylethyleneimine.", "content": "The results of experiments to investigate antibody to 'virus infection associated' (VIA) antigen in cattle repeatedly vaccinated with formalin- or acetylethyleneimine- (AEI) inactivated foot-and-mouth disease (FMD) vaccines under laboratory conditions are reported. Results are also presented from some vaccinated animals subsequently exposed to FMD infection. Antibody against VIA was not detected before and after the first vaccination with formalin or AEI-inactivated vaccine but did develop in all animals after the second formalin vaccination and persisted throughout the experiment. After the second AEI vaccination, 4 of 12 animals developed antibody which persisted for at least 37 days. This transient response in some cattle was repeated after successive vaccinations but, in general, more animals responded as the number of vaccinations increased. After exposure to infection a transient VIA antibody response was occasionally observed in immune AEI-vaccinated animals. Some immune repeatedly AEI-vaccinated cattle did not develop detectable VIA antibody after challenge despite the persistence of virus in oesophageal-pharyngeal (O/P) fluid. The presence of antibody to VIA antigen is not conclusive proof that vaccinated animals have been exposed to infection and field data must be interpreted with caution.", "contents": "Immune response to virus-infection-associated (VIA) antigen in cattle repeatedly vaccinated with foot-and-mouth disease virus inactivated by formalin or acetylethyleneimine. The results of experiments to investigate antibody to 'virus infection associated' (VIA) antigen in cattle repeatedly vaccinated with formalin- or acetylethyleneimine- (AEI) inactivated foot-and-mouth disease (FMD) vaccines under laboratory conditions are reported. Results are also presented from some vaccinated animals subsequently exposed to FMD infection. Antibody against VIA was not detected before and after the first vaccination with formalin or AEI-inactivated vaccine but did develop in all animals after the second formalin vaccination and persisted throughout the experiment. After the second AEI vaccination, 4 of 12 animals developed antibody which persisted for at least 37 days. This transient response in some cattle was repeated after successive vaccinations but, in general, more animals responded as the number of vaccinations increased. After exposure to infection a transient VIA antibody response was occasionally observed in immune AEI-vaccinated animals. Some immune repeatedly AEI-vaccinated cattle did not develop detectable VIA antibody after challenge despite the persistence of virus in oesophageal-pharyngeal (O/P) fluid. The presence of antibody to VIA antigen is not conclusive proof that vaccinated animals have been exposed to infection and field data must be interpreted with caution."}
{"id": "PMID:216747", "title": "Role of thymic hormone (THF) and of a thymic plasma recirculating factor (TPRF) in the modulation of human lymphocyte response to PHA and Con A.", "content": "The results presented here point to the possibility that calf thymus extracts contain, in addition to the thymic hormone (THF), a second component: thymic plasma recirculating factor (TPRF). THF, which is involved in the process of T cell maturation and has been characterized as a protein of m.w. 3000 eluted in the void volume of a G-10 Sephadex column (G-10-I), caused an increased level of intracellular cAMP in umbilical cord blood lymphocytes (UCBL). This is in agreement with our previous observation that THF plays a major role in the differentiation of T cells. The second active material, TPRF, also isolated from thymic extract, is of a molecular size below 500 and was eluted in a G-10 Sephadex column at the fourth protein peak; it seems to circulate in the blood. Previously, we had observed in impaired response of UCBL to PHA and Con A stimulation in the presence of dialyzed human plasma (DHP). Our present results indicate that this impaired response is restored exclusively by TPRF. A factor with TPRF-like activity was also isolated from the plasma of normal donors; yet it was not detected in the plasma of thymectomized patients suffering from myasthenia gravis (MG). This suggests that TPRF from plasma is thymus dependent. TPRF does not affect the level of intracellular cAMP in UCBL.", "contents": "Role of thymic hormone (THF) and of a thymic plasma recirculating factor (TPRF) in the modulation of human lymphocyte response to PHA and Con A. The results presented here point to the possibility that calf thymus extracts contain, in addition to the thymic hormone (THF), a second component: thymic plasma recirculating factor (TPRF). THF, which is involved in the process of T cell maturation and has been characterized as a protein of m.w. 3000 eluted in the void volume of a G-10 Sephadex column (G-10-I), caused an increased level of intracellular cAMP in umbilical cord blood lymphocytes (UCBL). This is in agreement with our previous observation that THF plays a major role in the differentiation of T cells. The second active material, TPRF, also isolated from thymic extract, is of a molecular size below 500 and was eluted in a G-10 Sephadex column at the fourth protein peak; it seems to circulate in the blood. Previously, we had observed in impaired response of UCBL to PHA and Con A stimulation in the presence of dialyzed human plasma (DHP). Our present results indicate that this impaired response is restored exclusively by TPRF. A factor with TPRF-like activity was also isolated from the plasma of normal donors; yet it was not detected in the plasma of thymectomized patients suffering from myasthenia gravis (MG). This suggests that TPRF from plasma is thymus dependent. TPRF does not affect the level of intracellular cAMP in UCBL."}
{"id": "PMID:216749", "title": "Characterization of thymus-derived lymphocyte subsets in acute Epstein-Barr virus-induced infectious mononucleosis.", "content": "Changes in thymus-derived (T) lymphocyte subpopulation numbers were studied in patients with acute and convalescent Epstein-Barr virus (EBV)-induced infectious mononucleosis (LM). T cell subsets were characterized by the presence of Fc receptors for IgG (TG), for IgM (TM) or by the absence of either receptor (Tnon-M, non-G). We found that in acute IM, total numbers of T and B lymphocytes were elevated (p less than 0.01). Of the T lymphocyte subsets, the total number of Tnon-M, non-G lymphocytes was increased six fold compared to normal subjects (p less than 0.001) and included the majority of the atypical T lymphocytes. The number of total TG and TM lymphocytes was moderately increased (p less than 0.05). In convalescent IM patients, the number of total T cells remained slightly elevated (p less than 0.02) whereas  proportions and absolute numbers of B lymphocytes and T cell subsets returned to near normal levels. Thus, acute Epstein-Barr virus-induced IM is associated with a T lymphocytosis which is composed predominantly of atypical T cells which lack detectable Fc receptors for IgG or IgM.", "contents": "Characterization of thymus-derived lymphocyte subsets in acute Epstein-Barr virus-induced infectious mononucleosis. Changes in thymus-derived (T) lymphocyte subpopulation numbers were studied in patients with acute and convalescent Epstein-Barr virus (EBV)-induced infectious mononucleosis (LM). T cell subsets were characterized by the presence of Fc receptors for IgG (TG), for IgM (TM) or by the absence of either receptor (Tnon-M, non-G). We found that in acute IM, total numbers of T and B lymphocytes were elevated (p less than 0.01). Of the T lymphocyte subsets, the total number of Tnon-M, non-G lymphocytes was increased six fold compared to normal subjects (p less than 0.001) and included the majority of the atypical T lymphocytes. The number of total TG and TM lymphocytes was moderately increased (p less than 0.05). In convalescent IM patients, the number of total T cells remained slightly elevated (p less than 0.02) whereas  proportions and absolute numbers of B lymphocytes and T cell subsets returned to near normal levels. Thus, acute Epstein-Barr virus-induced IM is associated with a T lymphocytosis which is composed predominantly of atypical T cells which lack detectable Fc receptors for IgG or IgM."}
{"id": "PMID:216752", "title": "Activation of latent murine cytomegalovirus infection: cocultivation, cell transfer, and the effect of immunosuppression.", "content": "No free virus was detectable in any organ of DBA/2 mice greater than or equal to 16 weeks after infection with murine cytomegalovirus. Spleens were free of free lytic virus six weeks after infection. Spleen cells from such mice were shown to be latently infected by three methods. First, virus was recovered by cocultivation of spleen cells for two weeks or longer on either syngeneic or allogeneic (CDI) embryonic fibroblast cultures. Second, virus was recovered from salivary glands of either syngeneic (DBA/2) or allogeneic (C57BL/10) mice that received 10(8) spleen cells. Recovery was enhanced by treatment of allogeneic recipients with cyclophosphamide but not with azathioprine. Third, latently infected mice, after treatment with either cyclophosphamide or azathioprine, developed free murine cytomegalovirus in their salivary glands. The last two findings parallel observations of human cytomegalovirus in immunosuppressed patients and in patients receiving latently infected cells during transplantation. Both cyclophosphamide and azathioprine elevated titers of free lytic virus in the salivary glands.", "contents": "Activation of latent murine cytomegalovirus infection: cocultivation, cell transfer, and the effect of immunosuppression. No free virus was detectable in any organ of DBA/2 mice greater than or equal to 16 weeks after infection with murine cytomegalovirus. Spleens were free of free lytic virus six weeks after infection. Spleen cells from such mice were shown to be latently infected by three methods. First, virus was recovered by cocultivation of spleen cells for two weeks or longer on either syngeneic or allogeneic (CDI) embryonic fibroblast cultures. Second, virus was recovered from salivary glands of either syngeneic (DBA/2) or allogeneic (C57BL/10) mice that received 10(8) spleen cells. Recovery was enhanced by treatment of allogeneic recipients with cyclophosphamide but not with azathioprine. Third, latently infected mice, after treatment with either cyclophosphamide or azathioprine, developed free murine cytomegalovirus in their salivary glands. The last two findings parallel observations of human cytomegalovirus in immunosuppressed patients and in patients receiving latently infected cells during transplantation. Both cyclophosphamide and azathioprine elevated titers of free lytic virus in the salivary glands."}
{"id": "PMID:216753", "title": "The natural history of recurrent facial-oral infection with herpes simplex virus.", "content": "Fifty-seven episodes of facial-oral infections with herpes simplex virus (HSV) (cold sores) were studied in 41 ambulatory patients. Patients were examined within 24 hr of the onset of symptoms and for five consecutive days. Clinical parameters were assessed, lesion size was measured, and daily cultures for virus were performed. HSV was isolated in 61% of the episodes and was HSV type 1 in all cases. Serum neutralizing antibody to HSV was measured initially and 21 days after the onset of symptoms. All patients had antibody initially, but a fourfold or greater rise in titer was seen in only four patients. Lesion size and stage of healing were compared in patients with virus-positive episodes and those with virus-negative episodes. These two groups were found to be clinically distinct. Virus-positive lesions were larger, and the rate of healing was slower. This finding provides the first clinical correlation associated with the presence of HSV in cold sores.", "contents": "The natural history of recurrent facial-oral infection with herpes simplex virus. Fifty-seven episodes of facial-oral infections with herpes simplex virus (HSV) (cold sores) were studied in 41 ambulatory patients. Patients were examined within 24 hr of the onset of symptoms and for five consecutive days. Clinical parameters were assessed, lesion size was measured, and daily cultures for virus were performed. HSV was isolated in 61% of the episodes and was HSV type 1 in all cases. Serum neutralizing antibody to HSV was measured initially and 21 days after the onset of symptoms. All patients had antibody initially, but a fourfold or greater rise in titer was seen in only four patients. Lesion size and stage of healing were compared in patients with virus-positive episodes and those with virus-negative episodes. These two groups were found to be clinically distinct. Virus-positive lesions were larger, and the rate of healing was slower. This finding provides the first clinical correlation associated with the presence of HSV in cold sores."}
{"id": "PMID:216754", "title": "Simplified radioimmunoassay for detection of human rotavirus in stools.", "content": "A simplified radioimmunoassay (RIA) technique was developed to facilitate the diagnosis of human rotavirus in stools of infants with diarrhea. This microtiter solid-phase RIA utilizes as a critical reagent hyperimmune serum against a tissue culture-grown simian rotavirus that is immunologically closely related to the human agent. One hundred thirteen pediatric stool samples were tested. Thiry-five specimens known to be positive for rotavirus by electron microscopy were also positive by RIA. All RIA-positive reactions (36) were shown to be specific for rotavirus by means of an antibody-blocking test. Nonspecific RIA-positive reactions were not encountered. This accurate, sensitive RIA technique is practical for use in diagnostic laboratories because critical serum reagents are prepared against culture-grown virus and not against rotavirus derived from carefully selected stools of humans or experimentally infected gnotobiotic animals.", "contents": "Simplified radioimmunoassay for detection of human rotavirus in stools. A simplified radioimmunoassay (RIA) technique was developed to facilitate the diagnosis of human rotavirus in stools of infants with diarrhea. This microtiter solid-phase RIA utilizes as a critical reagent hyperimmune serum against a tissue culture-grown simian rotavirus that is immunologically closely related to the human agent. One hundred thirteen pediatric stool samples were tested. Thiry-five specimens known to be positive for rotavirus by electron microscopy were also positive by RIA. All RIA-positive reactions (36) were shown to be specific for rotavirus by means of an antibody-blocking test. Nonspecific RIA-positive reactions were not encountered. This accurate, sensitive RIA technique is practical for use in diagnostic laboratories because critical serum reagents are prepared against culture-grown virus and not against rotavirus derived from carefully selected stools of humans or experimentally infected gnotobiotic animals."}
{"id": "PMID:216755", "title": "Countercurrent immunoelectrophoresis in the diagnosis of viral infections of the central nervous system.", "content": "Countercurrent immunoelectrophoresis was utilized in the study of 621 specimens of cerebrospinal fluid to determine the correlation of detection of viral antigens with the clinical diagnosis of aseptic meningitis and related viral infections. A panel of viral antisera was immunoelectrophoresed against 119 specimens from patients with suspected viral infections of the central nervous system (group I), 32 from patients with bacterial meningitis (group 2), and 470 from patients with no suspected infection of the nervous system (group 3). One or more precipitin bands were detected in 79% of specimens from group 1, 19% from group 2, and 4% from group 3. Paired acute- and convalescent-phase sera from 32 (78%) of 41 patients with precipitin bands detected by countercurrent immunoelectrophoresis demonstrated a fourfold or greater change in complement-fixing antibodies to the detected antigen. With refinements in antisera, countercurrent immunoelectrophoresis may become useful in the rapid laboratory diagnosis of viral infection of the central nervous system.", "contents": "Countercurrent immunoelectrophoresis in the diagnosis of viral infections of the central nervous system. Countercurrent immunoelectrophoresis was utilized in the study of 621 specimens of cerebrospinal fluid to determine the correlation of detection of viral antigens with the clinical diagnosis of aseptic meningitis and related viral infections. A panel of viral antisera was immunoelectrophoresed against 119 specimens from patients with suspected viral infections of the central nervous system (group I), 32 from patients with bacterial meningitis (group 2), and 470 from patients with no suspected infection of the nervous system (group 3). One or more precipitin bands were detected in 79% of specimens from group 1, 19% from group 2, and 4% from group 3. Paired acute- and convalescent-phase sera from 32 (78%) of 41 patients with precipitin bands detected by countercurrent immunoelectrophoresis demonstrated a fourfold or greater change in complement-fixing antibodies to the detected antigen. With refinements in antisera, countercurrent immunoelectrophoresis may become useful in the rapid laboratory diagnosis of viral infection of the central nervous system."}
{"id": "PMID:216756", "title": "Leukemia and lymphoma: infrequent manifestations of common viral infections? A review.", "content": "Horizontally transmitted viruses have been etiologically linked to leukemia and lymphoma in several higher mammals (gibbons, cows, and cats). In the best-studied example, the cat, feline leukemia virus is a common community-acquired virus that infrequently produces cancer. However, the infection and its complications (cancer) are not typical of infectious diseases. Epidemilogically, serologically, and virologically, infections with this type of virus can contradict classic infectious disease dogma. Therefore, previous studies that failed to link characteristics of infectious diseases (epidemiologic, serologic, or virologic) to human cancer must be cautiously interpreted. A link between retroviruses and/or DNA viruses and human lympho-reticular malignancies is hypothesized, and it is suggested that systematized nation-wide studies of selected cancer patients and their contacts be executed with the most sensitive and specific laboratory probes available.", "contents": "Leukemia and lymphoma: infrequent manifestations of common viral infections? A review. Horizontally transmitted viruses have been etiologically linked to leukemia and lymphoma in several higher mammals (gibbons, cows, and cats). In the best-studied example, the cat, feline leukemia virus is a common community-acquired virus that infrequently produces cancer. However, the infection and its complications (cancer) are not typical of infectious diseases. Epidemilogically, serologically, and virologically, infections with this type of virus can contradict classic infectious disease dogma. Therefore, previous studies that failed to link characteristics of infectious diseases (epidemiologic, serologic, or virologic) to human cancer must be cautiously interpreted. A link between retroviruses and/or DNA viruses and human lympho-reticular malignancies is hypothesized, and it is suggested that systematized nation-wide studies of selected cancer patients and their contacts be executed with the most sensitive and specific laboratory probes available."}
{"id": "PMID:216757", "title": "Impaired fibrin polymerization in viral hepatitis. Report of a case: probable identity of the inhibitor with beta2-microglobulin.", "content": "A case is described in which a patient developed TT prolongation and bleeding during CMV hepatitis following successful renal transplantation. Bence-Jones proteinuria was noted, but there was no other evidence of myeloma. Bence-Jones proteinuria, TT prolongation, and bleeding abated as hepatitis resolved. In vitro, a protein isolated from the patient's urine was capable of prolonging the TT markedly, but it did not impair thrombin esterase activity. The effect of the protein seemed to be inhibition of fibrin polymerization. Sephadex gel filtration revealed a single TT-prolonging peak at 11,000 daltons, containing kappa, lambda, and delta antigens. By radioimmunoassay, virtually all the protein present reacted as beta2-microglobulin. Incubation with anti-beta2-microglobulin antiserum markedly attenuated anticoagulant activity. The paraprotein observed transiently in this patient's urine during hepatitis had potent anticoagulant activity and may well have accounted for his abnormal TT and bleeding diathesis; this paraprotein was not distinguishable from beta2-microglobulin.", "contents": "Impaired fibrin polymerization in viral hepatitis. Report of a case: probable identity of the inhibitor with beta2-microglobulin. A case is described in which a patient developed TT prolongation and bleeding during CMV hepatitis following successful renal transplantation. Bence-Jones proteinuria was noted, but there was no other evidence of myeloma. Bence-Jones proteinuria, TT prolongation, and bleeding abated as hepatitis resolved. In vitro, a protein isolated from the patient's urine was capable of prolonging the TT markedly, but it did not impair thrombin esterase activity. The effect of the protein seemed to be inhibition of fibrin polymerization. Sephadex gel filtration revealed a single TT-prolonging peak at 11,000 daltons, containing kappa, lambda, and delta antigens. By radioimmunoassay, virtually all the protein present reacted as beta2-microglobulin. Incubation with anti-beta2-microglobulin antiserum markedly attenuated anticoagulant activity. The paraprotein observed transiently in this patient's urine during hepatitis had potent anticoagulant activity and may well have accounted for his abnormal TT and bleeding diathesis; this paraprotein was not distinguishable from beta2-microglobulin."}
{"id": "PMID:216760", "title": "Inhibition by vanadium of sodium and potassium dependent adenosinetriphosphatase derived from animal and human tissues.", "content": "Inhibition of adenosinetriphosphatase (ATPase) by vanadium pentoxide (dissolved in water or in sodium hydroxide solution) was studied in microsomal fractions and tissue homogenates of kidney, brain, and heart of several species, including humans (kidney only). In some preparations vanadium was found to be the most potent inhibitor of Na+  + K+ATPase activity so far reported. Concentrations of vanadium causing 50 percent inhibition of Na+ + K+ATPase activity ranged from 6 x 10(-8) to 5 x 10(-7) M in microsomal fractions and from 2 x 10(-7) to 1 x 10(-6) M in tissue homogenates. Renal and cardiac enzymes were more sensitive to vanadium than the brain enzyme, a phenomenon independent of enzyme specific activity. The enzyme in tissue homogenates was more resistant to vanadium than the microsomal enzyme derived from the same tissues, suggesting a presence in tissues of protective agents. Mg2+ ATPase, which contaminated the enzyme preparations to a variable degree, was 1,000-10,000 times more resistant to vanadium than was Na+ + K+ATPase. More detailed studies on the mechanism of inhibition were performed with dog and human kidney enzymes. The reversible nature of the inhibition was suggested by the fact that fractional inactivation of Na+ + K+ATPase by vanadium was independent of enzyme protein concentrations. The inhibitory effect was reduced by Na+ and increased by K+ or Mg2+. ATP alone, but not MgATP, antagonized the inhibition. This could mean that vanadium inhibits the Na+ + K+ATPase at the site activated by Na+, and that ATP protects the enzyme either by binding vanadium or by competing for a mutual receptor on the enzyme. The inhibition was reduced by bovine serum albumin, probably binding vanadium. The inhibition was also diminished by reducing agents, ascorbic acid and citric acid.", "contents": "Inhibition by vanadium of sodium and potassium dependent adenosinetriphosphatase derived from animal and human tissues. Inhibition of adenosinetriphosphatase (ATPase) by vanadium pentoxide (dissolved in water or in sodium hydroxide solution) was studied in microsomal fractions and tissue homogenates of kidney, brain, and heart of several species, including humans (kidney only). In some preparations vanadium was found to be the most potent inhibitor of Na+  + K+ATPase activity so far reported. Concentrations of vanadium causing 50 percent inhibition of Na+ + K+ATPase activity ranged from 6 x 10(-8) to 5 x 10(-7) M in microsomal fractions and from 2 x 10(-7) to 1 x 10(-6) M in tissue homogenates. Renal and cardiac enzymes were more sensitive to vanadium than the brain enzyme, a phenomenon independent of enzyme specific activity. The enzyme in tissue homogenates was more resistant to vanadium than the microsomal enzyme derived from the same tissues, suggesting a presence in tissues of protective agents. Mg2+ ATPase, which contaminated the enzyme preparations to a variable degree, was 1,000-10,000 times more resistant to vanadium than was Na+ + K+ATPase. More detailed studies on the mechanism of inhibition were performed with dog and human kidney enzymes. The reversible nature of the inhibition was suggested by the fact that fractional inactivation of Na+ + K+ATPase by vanadium was independent of enzyme protein concentrations. The inhibitory effect was reduced by Na+ and increased by K+ or Mg2+. ATP alone, but not MgATP, antagonized the inhibition. This could mean that vanadium inhibits the Na+ + K+ATPase at the site activated by Na+, and that ATP protects the enzyme either by binding vanadium or by competing for a mutual receptor on the enzyme. The inhibition was reduced by bovine serum albumin, probably binding vanadium. The inhibition was also diminished by reducing agents, ascorbic acid and citric acid."}
{"id": "PMID:216763", "title": "Extracellular cytolysis by activated macrophages and granulocytes. II. Hydrogen peroxide as a mediator of cytotoxicity.", "content": "When deprived of oxygen, Bacille Calmette-Gu\u00e9rin (BCG)-activated macrophages no longer lysed P388 lymphoma cells. Both H2O2 release and cytotoxicity by BCG-activated macrophages and by granulocytes triggered with phorbol myristate acetate (PMA) were markedly inhibited when the glucose concentration in the medium was reduced to 0.03 mM or less, or if glucose were replaced with galactose. Catalase abolished PMA-triggered cytotoxicity by both types of effector cells, whereas superoxide dismutase had no effect. Ferricytochrome C reduced the cytotoxicity of BCG-activated macrophages, an effect which was largely reversed by superoxide dismutase. 10 drugs, thought to quench singlet oxygen and/or scavenge hydroxyl radical, did not affect cytotoxicity in this system. Neither azide nor cyanide reduced cytolysis, but there was marked inhibition by lactoperoxidase and iodide. This suggested that cytotoxicity was not dependent upon myeloperoxidase, and that lactoperoxidase may have diverted H2O2 from the oxidation of target cells to oxidation of substances in serum. Mouse erythrocytes, although sensitive targets, interfered with the cytolysis of lymphoma cells, probably by competition for H2O2. Starch particles with covalently bound glucose oxidase resembled macrophages in their spatial relation to the target cells and in the flux of H2O2 they generated from their surface, but were not expected to produce any other potentially toxic products. Such particles lysed lymphoma cells, and the lysis was prevented by catalase. Neither arginase nor thymidine appeared to be involved in cytolysis by BCG-activated macrophages under the conditions used. These findings demonstrated that release of H2O2 was both necessary and sufficient for cytolysis by BCG-activated macrophages and by granulocytes when pharmacologically triggered.", "contents": "Extracellular cytolysis by activated macrophages and granulocytes. II. Hydrogen peroxide as a mediator of cytotoxicity. When deprived of oxygen, Bacille Calmette-Gu\u00e9rin (BCG)-activated macrophages no longer lysed P388 lymphoma cells. Both H2O2 release and cytotoxicity by BCG-activated macrophages and by granulocytes triggered with phorbol myristate acetate (PMA) were markedly inhibited when the glucose concentration in the medium was reduced to 0.03 mM or less, or if glucose were replaced with galactose. Catalase abolished PMA-triggered cytotoxicity by both types of effector cells, whereas superoxide dismutase had no effect. Ferricytochrome C reduced the cytotoxicity of BCG-activated macrophages, an effect which was largely reversed by superoxide dismutase. 10 drugs, thought to quench singlet oxygen and/or scavenge hydroxyl radical, did not affect cytotoxicity in this system. Neither azide nor cyanide reduced cytolysis, but there was marked inhibition by lactoperoxidase and iodide. This suggested that cytotoxicity was not dependent upon myeloperoxidase, and that lactoperoxidase may have diverted H2O2 from the oxidation of target cells to oxidation of substances in serum. Mouse erythrocytes, although sensitive targets, interfered with the cytolysis of lymphoma cells, probably by competition for H2O2. Starch particles with covalently bound glucose oxidase resembled macrophages in their spatial relation to the target cells and in the flux of H2O2 they generated from their surface, but were not expected to produce any other potentially toxic products. Such particles lysed lymphoma cells, and the lysis was prevented by catalase. Neither arginase nor thymidine appeared to be involved in cytolysis by BCG-activated macrophages under the conditions used. These findings demonstrated that release of H2O2 was both necessary and sufficient for cytolysis by BCG-activated macrophages and by granulocytes when pharmacologically triggered."}
{"id": "PMID:216764", "title": "G(AKSL2): a new cell surface antigen of the mouse related to the dualtropic mink cell focus-inducing class of murine leukemia virus detected by naturally occurring antibody.", "content": "Normal mouse sera were tested for cytotoxic antibody to surface antigens of cultured monolayer cells infected with AKR-derived ecotropic MuLV, xentropic MuLV, or dualtropic MCF 247 MuLV. Antibody to ecotropic MuLV-infected cells was found in a proportion of C57BL/6, C3Hf/Bi, AKR-Fv-1b, and (C3Hf/Bi X AKR)F1 mice, but not AKR or (AKR X C3Hf/Bi)F1 mice. Antibody to xenotropic MuLV-infected cells was virtually restricted to C57BL/6 mice. Antibody to MCF 247-infected cells was found in all strains tested, including AKR mice. Absorption analysis of (C3Hf/Bi x akr)f1 and AKR-Fv-1b sera with selective reactivity for MCF 247-infected cells showed that these sera recognize distinctive antigens on MCF 247-infected cells that are not present on ecotropic or xenotropic MuLV-infected cells. The transplantable AKR spontaneous leukemia AKSL2 was found to be uniquely sensitive to the cytotoxic action of naturally occurring antibody to MCF 247-related antigens and absorption tests with AKSL2 as the target cell and sera from a single AKR-Fv-1b mouse have permitted the definition of a new MuLV-related cell surface antigen, which has been designated G(AKSL2). Thymocytes from young mice of high leukemia-incidence strains (AKR, C58, and PL) express G(AKSL2), whereas thymocytes from 12 other strains do not. In AKR mice, the antigen is expressed in higher amounts on cells from thymus and bone marrow than on spleen cells. All AKR spontaneous leukemias tested express G(AKSL2), as did three MuLV-induced leukemias arising in G(AKSL2)- strains. Five X-ray-induced leukemias of G(AKSL2)- strains were G(AKSL2)-, as were MuLV+ and MuLV- chemically induced sarcomas. In the limited survey conducted to date, natural antibody to G(AKSL2) has been restricted to strains expressing G(AKSL2) in their normal tissues: AKR, AKR congenic mice AKR-Fv-1b and AKR hybrid mice (C3Hf/Bi x akr)f1 and (C57BL/6 X AKR)F1. In vitro G(AKSL2) induction tests involving MuLV infection of cultured monolayer cells showed that 8 of 12 newly isolated dualtropic MuLV shared the property of G(AKSL2) induction with the prototype MCF MuLV, MCF 247. Of the 12 ecotropic MuLV tested, only the N-tropic MuLV isolated from a leukemia originally induced by Passage A Gross virus induced G(AKSL2). The xenotropic and amphotropic MuLV isolates tested lacked G(AKSL2) inducing activity. Recognition of the g(aksl2) system provides a way to trace the origin and natural history of a class of dualtropic MCF MuLV in the mouse and to determine whether natural antibody to G(AKSL2) plays a role in AKR leukemogenesis.", "contents": "G(AKSL2): a new cell surface antigen of the mouse related to the dualtropic mink cell focus-inducing class of murine leukemia virus detected by naturally occurring antibody. Normal mouse sera were tested for cytotoxic antibody to surface antigens of cultured monolayer cells infected with AKR-derived ecotropic MuLV, xentropic MuLV, or dualtropic MCF 247 MuLV. Antibody to ecotropic MuLV-infected cells was found in a proportion of C57BL/6, C3Hf/Bi, AKR-Fv-1b, and (C3Hf/Bi X AKR)F1 mice, but not AKR or (AKR X C3Hf/Bi)F1 mice. Antibody to xenotropic MuLV-infected cells was virtually restricted to C57BL/6 mice. Antibody to MCF 247-infected cells was found in all strains tested, including AKR mice. Absorption analysis of (C3Hf/Bi x akr)f1 and AKR-Fv-1b sera with selective reactivity for MCF 247-infected cells showed that these sera recognize distinctive antigens on MCF 247-infected cells that are not present on ecotropic or xenotropic MuLV-infected cells. The transplantable AKR spontaneous leukemia AKSL2 was found to be uniquely sensitive to the cytotoxic action of naturally occurring antibody to MCF 247-related antigens and absorption tests with AKSL2 as the target cell and sera from a single AKR-Fv-1b mouse have permitted the definition of a new MuLV-related cell surface antigen, which has been designated G(AKSL2). Thymocytes from young mice of high leukemia-incidence strains (AKR, C58, and PL) express G(AKSL2), whereas thymocytes from 12 other strains do not. In AKR mice, the antigen is expressed in higher amounts on cells from thymus and bone marrow than on spleen cells. All AKR spontaneous leukemias tested express G(AKSL2), as did three MuLV-induced leukemias arising in G(AKSL2)- strains. Five X-ray-induced leukemias of G(AKSL2)- strains were G(AKSL2)-, as were MuLV+ and MuLV- chemically induced sarcomas. In the limited survey conducted to date, natural antibody to G(AKSL2) has been restricted to strains expressing G(AKSL2) in their normal tissues: AKR, AKR congenic mice AKR-Fv-1b and AKR hybrid mice (C3Hf/Bi x akr)f1 and (C57BL/6 X AKR)F1. In vitro G(AKSL2) induction tests involving MuLV infection of cultured monolayer cells showed that 8 of 12 newly isolated dualtropic MuLV shared the property of G(AKSL2) induction with the prototype MCF MuLV, MCF 247. Of the 12 ecotropic MuLV tested, only the N-tropic MuLV isolated from a leukemia originally induced by Passage A Gross virus induced G(AKSL2). The xenotropic and amphotropic MuLV isolates tested lacked G(AKSL2) inducing activity. Recognition of the g(aksl2) system provides a way to trace the origin and natural history of a class of dualtropic MCF MuLV in the mouse and to determine whether natural antibody to G(AKSL2) plays a role in AKR leukemogenesis."}
{"id": "PMID:216762", "title": "Inhibition of hepatic toxicities from polybrominated biphenyls and aflatoxin B in rats fed cauliflower.", "content": "Feeding diets containing cauliflower to rats inhibited hepatic residues of polybrominated biphenyls (PBB) with a reduction of fatty livers produced by 50 ppm of dietary PBB. Cauliflower diets also reduced the toxic effects of aflatoxin in Fischer rats, i.e. prevented mortality and internal hemorrhaging, and reduced liver pathology. These diets enhanced hepatic aminopyrine N-demethylase and p-nitroanisole O-demethylase activities. A kinetic study of aryl hydrocarbon hydroxylase reaction rates showed that apparent Km was lower in liver, kidney, and intestine, with a higher Vmax in the intestine. These data, combined with earlier studies, suggest that microsomal enzyme induction, especially in liver and intestine, affords a detoxication mechanism of two widespread food contaminants when animals are under a cauliflower dietary regimen.", "contents": "Inhibition of hepatic toxicities from polybrominated biphenyls and aflatoxin B in rats fed cauliflower. Feeding diets containing cauliflower to rats inhibited hepatic residues of polybrominated biphenyls (PBB) with a reduction of fatty livers produced by 50 ppm of dietary PBB. Cauliflower diets also reduced the toxic effects of aflatoxin in Fischer rats, i.e. prevented mortality and internal hemorrhaging, and reduced liver pathology. These diets enhanced hepatic aminopyrine N-demethylase and p-nitroanisole O-demethylase activities. A kinetic study of aryl hydrocarbon hydroxylase reaction rates showed that apparent Km was lower in liver, kidney, and intestine, with a higher Vmax in the intestine. These data, combined with earlier studies, suggest that microsomal enzyme induction, especially in liver and intestine, affords a detoxication mechanism of two widespread food contaminants when animals are under a cauliflower dietary regimen."}
{"id": "PMID:216765", "title": "Wild mouse RNA tumor viruses. A nongenetically transmitted virus group closely related to exogenous leukemia viruses of laboratory mouse strains.", "content": "Type-C RNA viruses isolated from wild mice are causative of naturally occurring neoplasia and neurologic diseases. Biochemical and immunologic characterization of this virus group revealed that amphotropic viruses isolated from wild mice trapped in separate geographical areas are indistinguishable, whereas amphotropic and ecotropic viruses naturally infecting the same animal are env gene variants. Molecular hybridization studies established that neither host range variant is endogenous to the Mus musculus genome, although each demonstrates partial nucleotide sequence homology. Wild mouse type-C viruses exhibited much closer molecular and antigenic relatedness to the exogenous virus subgroup (Friend-, Moloney-, and Rauscher-MuLV) than to prototype endogenous viruses isolated from laboratory mouse strains. The evidence indicates that exogenous mouse type-C viruses have been maintained in nature over a long period of evolution as a separate virus group, causative of tumors in mice by a mechanism solely involving their transmission as infectious agents.", "contents": "Wild mouse RNA tumor viruses. A nongenetically transmitted virus group closely related to exogenous leukemia viruses of laboratory mouse strains. Type-C RNA viruses isolated from wild mice are causative of naturally occurring neoplasia and neurologic diseases. Biochemical and immunologic characterization of this virus group revealed that amphotropic viruses isolated from wild mice trapped in separate geographical areas are indistinguishable, whereas amphotropic and ecotropic viruses naturally infecting the same animal are env gene variants. Molecular hybridization studies established that neither host range variant is endogenous to the Mus musculus genome, although each demonstrates partial nucleotide sequence homology. Wild mouse type-C viruses exhibited much closer molecular and antigenic relatedness to the exogenous virus subgroup (Friend-, Moloney-, and Rauscher-MuLV) than to prototype endogenous viruses isolated from laboratory mouse strains. The evidence indicates that exogenous mouse type-C viruses have been maintained in nature over a long period of evolution as a separate virus group, causative of tumors in mice by a mechanism solely involving their transmission as infectious agents."}
{"id": "PMID:216766", "title": "Bactericidal activity of a superoxide anion-generating system. A model for the polymorphonuclear leukocyte.", "content": "The acetaldehyde-xanthine oxidase system in the presence and absence of myeloperoxidase (MPO) and chloride has been employed as a model of the oxygen-dependent antimicrobial systems of the PMN. The unsupplemented xanthine oxidase system was bactericidal at relatively high acetaldehyde concentrations. The bactericidal activity was inhibited by superoxide dismutase (SOD), catalase, the hydroxyl radical (OH.) scavengers, mannitol and benzoate, the singlet oxygen (1O2) quenchers, azide, histidine, and 1,4-diazabicyclo[2,2,2]octane (DABCO) and by the purines, xanthine, hypoxanthine, and uric acid. The latter effect may account for the relatively weak bactericidal activity of the xanthine oxidase system when purines are employed as substrate. A white, carotenoid-negative mutant strain of Sarcina lutea was more susceptible to the acetaldehyde-xanthine oxidase system than was the yellow, carotenoid-positive parent strain. Carotenoid pigments are potent 1O2 quenchers. The xanthine oxidase system catalyzes the conversion of 2,5-diphenylfuran to cis-dibenzoylethylene, a reaction which can occur by a 1O2 mechanism. This conversion is inhibited by SOD, catalase, azide, histidine, DABCO, xanthine, hypoxanthine, and uric acid but is only slightly inhibited by mannitol and benzoate. The addition of MPO and chloride to the acetaldehyde-xanthine oxidase system greatly increases bactericidal activity; the minimal effective acetaldehyde concentration is decreased 100-fold and the rate and extent of bacterial killing is increased. The bactericidal activity of the MPO-supplemented system is inhibited by catalase, benzoate, azide, DABCO, and histidine but not by SOD or mannitol. Thus, the acetaldehyde-xanthine oxidase system which like phagocytosing PMNs generates superoxide (O.2-) and hydrogen peroxide, is bactericidal both in the presence and absence of MPO and chloride. The MPO-supplemented system is considerably more potent; however, when MPO is absent, bactericidal activity is observed which may be mediated by the interaction of H2O2 and O.2- to form OH. and 1O2.", "contents": "Bactericidal activity of a superoxide anion-generating system. A model for the polymorphonuclear leukocyte. The acetaldehyde-xanthine oxidase system in the presence and absence of myeloperoxidase (MPO) and chloride has been employed as a model of the oxygen-dependent antimicrobial systems of the PMN. The unsupplemented xanthine oxidase system was bactericidal at relatively high acetaldehyde concentrations. The bactericidal activity was inhibited by superoxide dismutase (SOD), catalase, the hydroxyl radical (OH.) scavengers, mannitol and benzoate, the singlet oxygen (1O2) quenchers, azide, histidine, and 1,4-diazabicyclo[2,2,2]octane (DABCO) and by the purines, xanthine, hypoxanthine, and uric acid. The latter effect may account for the relatively weak bactericidal activity of the xanthine oxidase system when purines are employed as substrate. A white, carotenoid-negative mutant strain of Sarcina lutea was more susceptible to the acetaldehyde-xanthine oxidase system than was the yellow, carotenoid-positive parent strain. Carotenoid pigments are potent 1O2 quenchers. The xanthine oxidase system catalyzes the conversion of 2,5-diphenylfuran to cis-dibenzoylethylene, a reaction which can occur by a 1O2 mechanism. This conversion is inhibited by SOD, catalase, azide, histidine, DABCO, xanthine, hypoxanthine, and uric acid but is only slightly inhibited by mannitol and benzoate. The addition of MPO and chloride to the acetaldehyde-xanthine oxidase system greatly increases bactericidal activity; the minimal effective acetaldehyde concentration is decreased 100-fold and the rate and extent of bacterial killing is increased. The bactericidal activity of the MPO-supplemented system is inhibited by catalase, benzoate, azide, DABCO, and histidine but not by SOD or mannitol. Thus, the acetaldehyde-xanthine oxidase system which like phagocytosing PMNs generates superoxide (O.2-) and hydrogen peroxide, is bactericidal both in the presence and absence of MPO and chloride. The MPO-supplemented system is considerably more potent; however, when MPO is absent, bactericidal activity is observed which may be mediated by the interaction of H2O2 and O.2- to form OH. and 1O2."}
{"id": "PMID:216767", "title": "Naturally occurring lymphocyte-mediated immunity to endogenous type-C virus in the mouse. Blocking of the lymphocyte reactivity with antisera to the virus.", "content": "The natural immune response in mice to their endogenous type-C viruses involves a complex interaction between cellular and humoral immune mechanisms. The virus-specific immune reactivities are a function of age and appear only subsequent to endogenous virus expression. Cellular immune activity was found to reside in a population of lymphocytes that were characterized as natural killer cells based on their absence of theta surface antigens or immunoglobulin or complement receptors. Cellular and humoral virus-specific immune responses co-occur in the same animal and pretreatment of virus-positive target cells with sera from virus-positive aging mice is capable of partially blocking the cytotoxic activity of reactive lymphocytes. The blocking activity of sera from individual mice increases as a function of age and endogenous virus expression and is highly correlated with the virus-specific complement-dependent cytotoxic activity of these sera. Mouse sera, whether naturally immune or immune as a result of hyperimmunization with type-C virus, exhibit blocking activity that can be removed by absorption with purified type-C virus or purified viral glycoprotein (gp 70) but not by absorption with noninfected syngeneic cells. High-titered and highly specific antisera directed against certain individual R-MuLV structural proteins reveal blocking activity. Monospecific antisera to gp 70 and p 12 exhibited high-titered blocking reactivities which are absorbable by the respective purified proteins. Blocking activity of antisera directed against other viral structural proteins could not be excluded with certainty. These findings raise the possibility that immunity in the mouse to endogenous type-C virus or virus-infected cells involves competition between serum-blocking activity and natural-killer cell activity and further provides a unique model system for studying the mechanism of action of blocking antisera known to have monospecific reactivity against defined and purifiable transplantation antigens.", "contents": "Naturally occurring lymphocyte-mediated immunity to endogenous type-C virus in the mouse. Blocking of the lymphocyte reactivity with antisera to the virus. The natural immune response in mice to their endogenous type-C viruses involves a complex interaction between cellular and humoral immune mechanisms. The virus-specific immune reactivities are a function of age and appear only subsequent to endogenous virus expression. Cellular immune activity was found to reside in a population of lymphocytes that were characterized as natural killer cells based on their absence of theta surface antigens or immunoglobulin or complement receptors. Cellular and humoral virus-specific immune responses co-occur in the same animal and pretreatment of virus-positive target cells with sera from virus-positive aging mice is capable of partially blocking the cytotoxic activity of reactive lymphocytes. The blocking activity of sera from individual mice increases as a function of age and endogenous virus expression and is highly correlated with the virus-specific complement-dependent cytotoxic activity of these sera. Mouse sera, whether naturally immune or immune as a result of hyperimmunization with type-C virus, exhibit blocking activity that can be removed by absorption with purified type-C virus or purified viral glycoprotein (gp 70) but not by absorption with noninfected syngeneic cells. High-titered and highly specific antisera directed against certain individual R-MuLV structural proteins reveal blocking activity. Monospecific antisera to gp 70 and p 12 exhibited high-titered blocking reactivities which are absorbable by the respective purified proteins. Blocking activity of antisera directed against other viral structural proteins could not be excluded with certainty. These findings raise the possibility that immunity in the mouse to endogenous type-C virus or virus-infected cells involves competition between serum-blocking activity and natural-killer cell activity and further provides a unique model system for studying the mechanism of action of blocking antisera known to have monospecific reactivity against defined and purifiable transplantation antigens."}
{"id": "PMID:216768", "title": "Primary anti-viral cytotoxic T-cell responses in semiallogeneic chimeras are not absolutely restricted to host H-2 type.", "content": "Chimeras produced by reconstitution of 950 rads irradiated type A or type B host mice with (AXB)F1 fetal liver stem cells were examined in primary (in vivo) and secondary (in vitro) Tc-cell responses to ectromelia virus infection. Of 33 individual chimeras which gave primary responses, 26 produced significant specific lysis of infected targets of both A and B type, though host type targets were invariably lysed more efficiently (host bias). The other 7 chimeras gave lysis of infected host type targets only (absolute restriction). 12 individual chimeras were used in secondary responses. Nine showed host bias, and three showed absolute restriction. Whether an individual chimera showed host bias or absolute restriction seemed to be unrelated to whether the response was primary or secondary, to the time after reconstitution (ranging from 4 to 22 wk), to strain of mouse, or to the batch of fetal liver stem cells used.", "contents": "Primary anti-viral cytotoxic T-cell responses in semiallogeneic chimeras are not absolutely restricted to host H-2 type. Chimeras produced by reconstitution of 950 rads irradiated type A or type B host mice with (AXB)F1 fetal liver stem cells were examined in primary (in vivo) and secondary (in vitro) Tc-cell responses to ectromelia virus infection. Of 33 individual chimeras which gave primary responses, 26 produced significant specific lysis of infected targets of both A and B type, though host type targets were invariably lysed more efficiently (host bias). The other 7 chimeras gave lysis of infected host type targets only (absolute restriction). 12 individual chimeras were used in secondary responses. Nine showed host bias, and three showed absolute restriction. Whether an individual chimera showed host bias or absolute restriction seemed to be unrelated to whether the response was primary or secondary, to the time after reconstitution (ranging from 4 to 22 wk), to strain of mouse, or to the batch of fetal liver stem cells used."}
{"id": "PMID:216769", "title": "Time saving protein binding assay for the simultaneous determination of guanosine 3':5'-monophosphate (cGMP) and adenosine 3':5'-monophosphate (cAMP) in human urine.", "content": "A time-saving protein binding assay for the simultaneous determination of cGMP and cAMP has been adapted for human urine, using [3H]cGMP, [14C]cAMP, protein fractions from calf skeletal and lobster tail muscles and the phosphodiesterase inhibitor SQ 20.009. Recovery, accuracy, and precision are approximately at the 10% limit. Good specificity and no interference were observed with diluted urine samples (10 to 20 times).", "contents": "Time saving protein binding assay for the simultaneous determination of guanosine 3':5'-monophosphate (cGMP) and adenosine 3':5'-monophosphate (cAMP) in human urine. A time-saving protein binding assay for the simultaneous determination of cGMP and cAMP has been adapted for human urine, using [3H]cGMP, [14C]cAMP, protein fractions from calf skeletal and lobster tail muscles and the phosphodiesterase inhibitor SQ 20.009. Recovery, accuracy, and precision are approximately at the 10% limit. Good specificity and no interference were observed with diluted urine samples (10 to 20 times)."}
{"id": "PMID:216773", "title": "Increased cyclic GMP in the end-plate region of denervated frog muscle.", "content": "Denervated frog sartorius muscles showed an approximately 2--3 fold increase of cyclic GMP in their end-plate rich regions which did not appear up to 5 weeks after denervation in the normally end-plate-free pelvic region. No increase in cyclic AMP was seen in these preparations. The results suggest that the increase of cyclic GMP is related to processes specific to the region in which end plates are normally present.", "contents": "Increased cyclic GMP in the end-plate region of denervated frog muscle. Denervated frog sartorius muscles showed an approximately 2--3 fold increase of cyclic GMP in their end-plate rich regions which did not appear up to 5 weeks after denervation in the normally end-plate-free pelvic region. No increase in cyclic AMP was seen in these preparations. The results suggest that the increase of cyclic GMP is related to processes specific to the region in which end plates are normally present."}
{"id": "PMID:216781", "title": "Changes in motor unit populations in motor neurone disease.", "content": "In motor neurone disease changes in the functional properties of motor units, including the surface voltage, latency, conduction velocity, and response to repetitive stimulation, were investigated. Progression was marked by motor unit loss, increase in the proportion of larger motor unit potentials, and inclusion of motor unit potentials larger than normal in the remaining motor unit population. Even late in the disease, motor unit potentials with a low surface voltage persisted. The relationship between motor unit potentials, surface voltage, and latency, present in control subjects, broke down in motor neurone disease, large motor unit potentials having abnormally long latencies and small motor unit potentials unexpectedly short latencies. Amplitude decrements were more frequent and severe in motor unit potentials at later stages in the disease, particularly in those units with lower surface voltages. In one surviving motor unit potential there was evidence suggestive of functional recovery. The observations point to complex changes in the functional properties of motor units in motor neurone disease.", "contents": "Changes in motor unit populations in motor neurone disease. In motor neurone disease changes in the functional properties of motor units, including the surface voltage, latency, conduction velocity, and response to repetitive stimulation, were investigated. Progression was marked by motor unit loss, increase in the proportion of larger motor unit potentials, and inclusion of motor unit potentials larger than normal in the remaining motor unit population. Even late in the disease, motor unit potentials with a low surface voltage persisted. The relationship between motor unit potentials, surface voltage, and latency, present in control subjects, broke down in motor neurone disease, large motor unit potentials having abnormally long latencies and small motor unit potentials unexpectedly short latencies. Amplitude decrements were more frequent and severe in motor unit potentials at later stages in the disease, particularly in those units with lower surface voltages. In one surviving motor unit potential there was evidence suggestive of functional recovery. The observations point to complex changes in the functional properties of motor units in motor neurone disease."}
{"id": "PMID:216782", "title": "Concentration of homovanillic acid and 5-hydroxyindoleacetic acid in the ventricular cerebrospinal fluid of patients with obstructive hydrocephalus.", "content": "In 12 patients with different posterior fossa tumours the concentrations of homovanillic acid (HVA) and of 5-hydroxyindoleacetic acid (5-HIAA) were measured in cerebrospinal fluid from the lateral ventricles. All patients had obstructive hydrocephalus. Patients with a clear increase of 5-HIAA/HVA ratio in the ventricular CSF have died subsequently. This feature may have a diagnostic value, and indicates the prevalence of serotoninergic neurones in patients with obstructive hydrocephalus with fatal course after surgery.", "contents": "Concentration of homovanillic acid and 5-hydroxyindoleacetic acid in the ventricular cerebrospinal fluid of patients with obstructive hydrocephalus. In 12 patients with different posterior fossa tumours the concentrations of homovanillic acid (HVA) and of 5-hydroxyindoleacetic acid (5-HIAA) were measured in cerebrospinal fluid from the lateral ventricles. All patients had obstructive hydrocephalus. Patients with a clear increase of 5-HIAA/HVA ratio in the ventricular CSF have died subsequently. This feature may have a diagnostic value, and indicates the prevalence of serotoninergic neurones in patients with obstructive hydrocephalus with fatal course after surgery."}
{"id": "PMID:216783", "title": "Influence of site of origin of lung carcinomas on clinical presentation and central nervous system metastases.", "content": "A retrospective survey of 100 patients dying from carcinoma of the lung showed that neurological presentation and central nervous system metastases are more frequently present when the primary carcinoma is situated in the peripheral lung tissue (including lung apex). The high incidence of cases presenting neurologically and the high incidence of single secondary deposits involving the central nervous system from peripheral or apical growths suggest a difference in the mode of spread or other properties of such growths compared with the more common central carcinoma.", "contents": "Influence of site of origin of lung carcinomas on clinical presentation and central nervous system metastases. A retrospective survey of 100 patients dying from carcinoma of the lung showed that neurological presentation and central nervous system metastases are more frequently present when the primary carcinoma is situated in the peripheral lung tissue (including lung apex). The high incidence of cases presenting neurologically and the high incidence of single secondary deposits involving the central nervous system from peripheral or apical growths suggest a difference in the mode of spread or other properties of such growths compared with the more common central carcinoma."}
{"id": "PMID:216786", "title": "Ulcerative diseases of animals with an infectious etiology.", "content": "The oral lesions of five viral diseases of cattle are compared. Two of the diseases, foot-and-mouth disease and vesicular stomatitis, cause vesicles, and rinderpest, bovine virus diarrhea and malignant catarrhal fever produce sharply demarcated erosive lesions. Gross lesions of different diseases appear similar: however, histologically, there are subtle differences in the development of the lesions.", "contents": "Ulcerative diseases of animals with an infectious etiology. The oral lesions of five viral diseases of cattle are compared. Two of the diseases, foot-and-mouth disease and vesicular stomatitis, cause vesicles, and rinderpest, bovine virus diarrhea and malignant catarrhal fever produce sharply demarcated erosive lesions. Gross lesions of different diseases appear similar: however, histologically, there are subtle differences in the development of the lesions."}
{"id": "PMID:216784", "title": "An immunoperoxidase study on herpes simplex virus encephalitis.", "content": "Using formalin-fixed, paraffin-embedded sections, indirect immunoperoxidase studies were performed on 3 autopsied and 1 biopsied cases of herpes simplex virus (HSV) encephalitis. Specific reaction was observed in all 4 cases. Distinct stain was observed both in neurons and in glial cells. Electron microscopic studies performed on the same material revealed HSV particles stained with electron-dense reaction products. The advantages and disadvantages of the use of formalin-fixed, paraffin-embedded material in immunoperoxidase studies of viral disease are discussed.", "contents": "An immunoperoxidase study on herpes simplex virus encephalitis. Using formalin-fixed, paraffin-embedded sections, indirect immunoperoxidase studies were performed on 3 autopsied and 1 biopsied cases of herpes simplex virus (HSV) encephalitis. Specific reaction was observed in all 4 cases. Distinct stain was observed both in neurons and in glial cells. Electron microscopic studies performed on the same material revealed HSV particles stained with electron-dense reaction products. The advantages and disadvantages of the use of formalin-fixed, paraffin-embedded material in immunoperoxidase studies of viral disease are discussed."}
{"id": "PMID:216787", "title": "Scanning electron microscopy of retinoblastoma.", "content": "Two cases of the so-called undifferentiated retinoblastoma are demonstrated where typical rosettes were absent. However, cell groups resembling rosettes existed. Scanning electron microscopy revealed a tendency of the cells to arrange in circles or in garland-like formations. In one of the cases lymphocytes were found and in the other photoreceptor elements and tubuloreticular inclusions within the endothelial cells were seen.", "contents": "Scanning electron microscopy of retinoblastoma. Two cases of the so-called undifferentiated retinoblastoma are demonstrated where typical rosettes were absent. However, cell groups resembling rosettes existed. Scanning electron microscopy revealed a tendency of the cells to arrange in circles or in garland-like formations. In one of the cases lymphocytes were found and in the other photoreceptor elements and tubuloreticular inclusions within the endothelial cells were seen."}
{"id": "PMID:216792", "title": "Effects of local anesthesia on gingival cAMP levels.", "content": "The basal levels of cAMP in the attached gingiva of Rhesus monkeys and the changes in tissue cAMP levels produced by infiltration anesthesia with lidocaine and lidocaine containing 1:100,000 epinephrine were studied. The basal level of cAMP in uninjected monkey gingiva ranged from 12 to 20 picomoles of cAMP per mg of gingival protein. This level was 75 times greater than the cAMP content of monkey blood plasma. Infiltration of the attached gingiva with saline or plain lidocaine for 5 minutes did not produce any significant changes in tissue cAMP levels. Infiltration of the gingiva with lidocaine containing 1:100,000 epinephrine, on the other hand, caused a very marked increase in tissue cAMP levels. Thirty seconds after infiltration with lidocaine with 1:100,000 epinephrine there was a 250% increase in cAMP content of the anesthetized tissue versus the uninjected control tissues. The maximal increase in tissue cAMP levels was observed 5 minutes after infiltration when the cAMP content of the gingiva was 1000 to 1100% above the control level. It is proposed that regulation of tissue cAMP levels by epinephrine or other agents may prove of therapeutic usefulness in regulating inflammation and healing of tissues after surgery or other trauma.", "contents": "Effects of local anesthesia on gingival cAMP levels. The basal levels of cAMP in the attached gingiva of Rhesus monkeys and the changes in tissue cAMP levels produced by infiltration anesthesia with lidocaine and lidocaine containing 1:100,000 epinephrine were studied. The basal level of cAMP in uninjected monkey gingiva ranged from 12 to 20 picomoles of cAMP per mg of gingival protein. This level was 75 times greater than the cAMP content of monkey blood plasma. Infiltration of the attached gingiva with saline or plain lidocaine for 5 minutes did not produce any significant changes in tissue cAMP levels. Infiltration of the gingiva with lidocaine containing 1:100,000 epinephrine, on the other hand, caused a very marked increase in tissue cAMP levels. Thirty seconds after infiltration with lidocaine with 1:100,000 epinephrine there was a 250% increase in cAMP content of the anesthetized tissue versus the uninjected control tissues. The maximal increase in tissue cAMP levels was observed 5 minutes after infiltration when the cAMP content of the gingiva was 1000 to 1100% above the control level. It is proposed that regulation of tissue cAMP levels by epinephrine or other agents may prove of therapeutic usefulness in regulating inflammation and healing of tissues after surgery or other trauma."}
{"id": "PMID:216790", "title": "Systemic and topical use of poly I.C. in treatment of generalized neonatal herpes simplex infection with severe ocular involvement.", "content": "A case of Neonatal Herpes Simlex Virus (RSV) Encephalitis with severe ocular manifestation treated by topical systemic and intrathecal Interferon inducer, Poly IC (Polyriboinosinic acid-Polyribocytidylic acid) is reported. Prior to the administration of Poly IC, no Interferon could be detected neither in blood nor in CSF and vesicular fluid from conjunctiva. Intravenous administration of the drug initiated measurable levels in blood and tears, but not in CSF. However, intrathecal injection induced persistent high levels of Interferon in CSF. Virus clearance from conjunctiva tears and vesicular fluid occurred after three days of topical application of Poly IC. The mechanism of action of Poly IC, the laboratory results and the therapeutic conclusions are discussed in detail. This is the first report of intrathecal administration of Poly IC in a case of HSV Encephalitis.", "contents": "Systemic and topical use of poly I.C. in treatment of generalized neonatal herpes simplex infection with severe ocular involvement. A case of Neonatal Herpes Simlex Virus (RSV) Encephalitis with severe ocular manifestation treated by topical systemic and intrathecal Interferon inducer, Poly IC (Polyriboinosinic acid-Polyribocytidylic acid) is reported. Prior to the administration of Poly IC, no Interferon could be detected neither in blood nor in CSF and vesicular fluid from conjunctiva. Intravenous administration of the drug initiated measurable levels in blood and tears, but not in CSF. However, intrathecal injection induced persistent high levels of Interferon in CSF. Virus clearance from conjunctiva tears and vesicular fluid occurred after three days of topical application of Poly IC. The mechanism of action of Poly IC, the laboratory results and the therapeutic conclusions are discussed in detail. This is the first report of intrathecal administration of Poly IC in a case of HSV Encephalitis."}
{"id": "PMID:216789", "title": "Cerebral gigantism (Sotos' syndrome) and cataracts.", "content": "A five-year-old girl with cerebral gigantism (Sotos' syndrome) and cataracts is described. Sotos' syndrome, characterized by generalized gigantism with normal endocrine studies has rarely been reported with ocular abnormalities and never with cataracts. It is important to study any child with cataracts for systemic disease.", "contents": "Cerebral gigantism (Sotos' syndrome) and cataracts. A five-year-old girl with cerebral gigantism (Sotos' syndrome) and cataracts is described. Sotos' syndrome, characterized by generalized gigantism with normal endocrine studies has rarely been reported with ocular abnormalities and never with cataracts. It is important to study any child with cataracts for systemic disease."}
{"id": "PMID:216795", "title": "The role of sulfhydryl groups in contraction of vascular smooth muscle.", "content": "While high concentrations (50 micronmol/l) of merurial sulfhydryl (SH) reagents p-chloromercuribenzoate (PCMB) and p-chloromercuriphenyl sulfate (PCMPS) caused a nonspecific inhibition of constrictor responses in isolated rabbit ear arteries, lower concentrations had selective effects. At a concentration of 10 micronmol/l both agents abolished responses to epinephrine and reduced responses to barium and calcium, but responses to caffeine were unaffected by PCMB and potentiated by PCMPS. Responses to histamine were little affected by PCMPS, but with PCMB, histamine responses were first reduced but later potentiated. In contrast, ethacrynic acid, a nonmercurial SH inhibitor which gains access to the intracellular space, failed to show any specificity of action and inhibited contractile responses to all these agonists. The results suggest that SH inhibitors whose actions are limited to the cell membrane exert both specific and nonspecific effects. The specific effect may be at SH groups associated with the alpha adrenoceptor while nonspecific effects may involve changes in membrane permeability.", "contents": "The role of sulfhydryl groups in contraction of vascular smooth muscle. While high concentrations (50 micronmol/l) of merurial sulfhydryl (SH) reagents p-chloromercuribenzoate (PCMB) and p-chloromercuriphenyl sulfate (PCMPS) caused a nonspecific inhibition of constrictor responses in isolated rabbit ear arteries, lower concentrations had selective effects. At a concentration of 10 micronmol/l both agents abolished responses to epinephrine and reduced responses to barium and calcium, but responses to caffeine were unaffected by PCMB and potentiated by PCMPS. Responses to histamine were little affected by PCMPS, but with PCMB, histamine responses were first reduced but later potentiated. In contrast, ethacrynic acid, a nonmercurial SH inhibitor which gains access to the intracellular space, failed to show any specificity of action and inhibited contractile responses to all these agonists. The results suggest that SH inhibitors whose actions are limited to the cell membrane exert both specific and nonspecific effects. The specific effect may be at SH groups associated with the alpha adrenoceptor while nonspecific effects may involve changes in membrane permeability."}
{"id": "PMID:216796", "title": "[Electrotonic transmission in the mammalian central nervous system (author's transl].", "content": "The aim of this review is to present the electrophysiological data, obtained in the mammalian central nervous system, which show that depolarisations recorded intracellularly, under certain experimental conditions can be interpreted in terms of electrotonic coupling. The results were obtained from very different structures: primary sensory nuclei, sensori-motor integration centres and motor nuclei. The association of the phenomenon of electrotonic transmission with a known ultrastructural substrate--the \"gap junction\"--has been defined by the term electrotonic coupling. In the cases where it has not been possible to link depolarisations with the presence of gap junctions, other possible morphological correlates have been envisaged. The functional significance of electrotonic interactions are discussed on the basis of information obtained from different experimental approaches.", "contents": "[Electrotonic transmission in the mammalian central nervous system (author's transl]. The aim of this review is to present the electrophysiological data, obtained in the mammalian central nervous system, which show that depolarisations recorded intracellularly, under certain experimental conditions can be interpreted in terms of electrotonic coupling. The results were obtained from very different structures: primary sensory nuclei, sensori-motor integration centres and motor nuclei. The association of the phenomenon of electrotonic transmission with a known ultrastructural substrate--the \"gap junction\"--has been defined by the term electrotonic coupling. In the cases where it has not been possible to link depolarisations with the presence of gap junctions, other possible morphological correlates have been envisaged. The functional significance of electrotonic interactions are discussed on the basis of information obtained from different experimental approaches."}
{"id": "PMID:216788", "title": "Effect of silver nitrate application on the conjunctival flora of the newborn: and the occurrence of clostridial conjunctivitis.", "content": "Newborn conjunctival cultures were obtained from 35 babies prior to silver nitrate application and 48 hours later. On initial culture, 46 facultative bacteria and 27 anaerobes were recovered; 48 facultative and 18 anaerobes were recovered after 48 hours. Haemophilus vaginalis, Bacteroides species and anaerobic cocci decreased in numbers, whereas S. epidermidis, Micrococcus and Propionibacterium acnes increased during this time interval. Clostridial species were isolated from two cases who developed conjunctivitis, along with Peptostreptococcus in one of the cases. In vitro experiments demonstrated lack of killing of C. perfringens in silver nitrate concentrations of 0.1 percent, even after 24 hours exposure.", "contents": "Effect of silver nitrate application on the conjunctival flora of the newborn: and the occurrence of clostridial conjunctivitis. Newborn conjunctival cultures were obtained from 35 babies prior to silver nitrate application and 48 hours later. On initial culture, 46 facultative bacteria and 27 anaerobes were recovered; 48 facultative and 18 anaerobes were recovered after 48 hours. Haemophilus vaginalis, Bacteroides species and anaerobic cocci decreased in numbers, whereas S. epidermidis, Micrococcus and Propionibacterium acnes increased during this time interval. Clostridial species were isolated from two cases who developed conjunctivitis, along with Peptostreptococcus in one of the cases. In vitro experiments demonstrated lack of killing of C. perfringens in silver nitrate concentrations of 0.1 percent, even after 24 hours exposure."}
{"id": "PMID:216801", "title": "Clonal growth of Entamoeba histolytica and other species of Entamoeba in agar.", "content": "This is the first description of a method for growing axenized Entamoeba histolytica as colonies from single cells in agar suspension. Factors affecting the efficiency of colony formation included unknown characteristics of the amebal strain, age of cells used, and the type and concentration of agar employed. Colony formation was dependent upon filling deep vessels (culture tubes or tissue culture flasks) with agar, probably to maintain reduced oxygen tension, and upon solidifying the agar rapidly at 0 C. It was demonstrated in a study with the drug metronidazole that the agar colony method was useful for quantifying cell viability in drug testing. Eleven of 12 E. histolytica strains tested, as well as one Entamoeba terrapinae, one Entamoeba barreti, and 3 Entamoeba invadens strains formed colonies in agar suspension. E. histolytica-like amebae (Laredo type) and E. moshkovskii formed only tiny colonies in agar.", "contents": "Clonal growth of Entamoeba histolytica and other species of Entamoeba in agar. This is the first description of a method for growing axenized Entamoeba histolytica as colonies from single cells in agar suspension. Factors affecting the efficiency of colony formation included unknown characteristics of the amebal strain, age of cells used, and the type and concentration of agar employed. Colony formation was dependent upon filling deep vessels (culture tubes or tissue culture flasks) with agar, probably to maintain reduced oxygen tension, and upon solidifying the agar rapidly at 0 C. It was demonstrated in a study with the drug metronidazole that the agar colony method was useful for quantifying cell viability in drug testing. Eleven of 12 E. histolytica strains tested, as well as one Entamoeba terrapinae, one Entamoeba barreti, and 3 Entamoeba invadens strains formed colonies in agar suspension. E. histolytica-like amebae (Laredo type) and E. moshkovskii formed only tiny colonies in agar."}
{"id": "PMID:216802", "title": "Pyridoxine kinase in Plasmodium lophurae and duckling erythrocytes.", "content": "Pyridoxine kinase enzyme activity was greatly increased in duckling erythrocytes infected with Plasmodium lophurae. Pyridoxine kinase activity in parasites freed from erythrocytes was much greater than that of uninfected erythrocytes. The apparent Km for pyridoxine of the parasite enzyme was 6.6 times 10(-5) M whereas the host red cell enzyme Km was 1.9 times 10(-6) M. Deoxypyridoxine inhibited host and parasite pyridoxine kinase activity with an apparent Ki of 1.5 times 10(-6) and 8.6 times 10(-6) M, respectively. These results suggest that the vitamin B6 metabolism of the malaria parasites is distinct and separate from that of the host erythrocytes.", "contents": "Pyridoxine kinase in Plasmodium lophurae and duckling erythrocytes. Pyridoxine kinase enzyme activity was greatly increased in duckling erythrocytes infected with Plasmodium lophurae. Pyridoxine kinase activity in parasites freed from erythrocytes was much greater than that of uninfected erythrocytes. The apparent Km for pyridoxine of the parasite enzyme was 6.6 times 10(-5) M whereas the host red cell enzyme Km was 1.9 times 10(-6) M. Deoxypyridoxine inhibited host and parasite pyridoxine kinase activity with an apparent Ki of 1.5 times 10(-6) and 8.6 times 10(-6) M, respectively. These results suggest that the vitamin B6 metabolism of the malaria parasites is distinct and separate from that of the host erythrocytes."}
{"id": "PMID:216803", "title": "Calcium pyrophosphate crystal deposition disease and hyperparathyroidism: a controlled, prospective study.", "content": "A prospective, controlled study of patients with primary hyperparathyroidism has been carried out to establish the relation of this endocrinopathy to calcium pyrophosphate dihydrate crystal deposition disease. Eight of 26 patients with documented hyperparathyroidism were found to have chondrocalcinosis compared to four of 104 individuals in the control group (p less than 0.01). Two of these eight patients had confirmed pseudogout attacks shortly after parathyroidectomy. Four other patients, including two without chondrocalcinosis, gave a history of typical pseudogout. Patients with hyperparathyroidism and chondrocalcinosis were significantly older than those without the articular lesion (p = 0.006). We could not delineate specific metabolic abnormalities of hyperparathyroidism which contributed to the development of chondrocalcinosis.", "contents": "Calcium pyrophosphate crystal deposition disease and hyperparathyroidism: a controlled, prospective study. A prospective, controlled study of patients with primary hyperparathyroidism has been carried out to establish the relation of this endocrinopathy to calcium pyrophosphate dihydrate crystal deposition disease. Eight of 26 patients with documented hyperparathyroidism were found to have chondrocalcinosis compared to four of 104 individuals in the control group (p less than 0.01). Two of these eight patients had confirmed pseudogout attacks shortly after parathyroidectomy. Four other patients, including two without chondrocalcinosis, gave a history of typical pseudogout. Patients with hyperparathyroidism and chondrocalcinosis were significantly older than those without the articular lesion (p = 0.006). We could not delineate specific metabolic abnormalities of hyperparathyroidism which contributed to the development of chondrocalcinosis."}
{"id": "PMID:216804", "title": "Calcium pyrophosphate dihydrate crystal formation in model hydrogels.", "content": "Using powder x-ray diffraction analysis, we studied calcium pyrophosphate crystal formation in silica and gelatin gels was well as in comparable aqueous solutions. We demonstrated that the physiological salts, monoclinic and triclinic calcium pyrophosphate dihydrate can be formed in gels and that gels do affect the type of crystals formed from ions in solution. These observations support our hypothesis that calcium pyrophosphate dihydrate crystal deposition in joints is regulated by the physical chemical gel state of the connective tissue matrix.", "contents": "Calcium pyrophosphate dihydrate crystal formation in model hydrogels. Using powder x-ray diffraction analysis, we studied calcium pyrophosphate crystal formation in silica and gelatin gels was well as in comparable aqueous solutions. We demonstrated that the physiological salts, monoclinic and triclinic calcium pyrophosphate dihydrate can be formed in gels and that gels do affect the type of crystals formed from ions in solution. These observations support our hypothesis that calcium pyrophosphate dihydrate crystal deposition in joints is regulated by the physical chemical gel state of the connective tissue matrix."}
{"id": "PMID:216805", "title": "A new form of Niemann-Pick disease characterised by temperature-labile sphingomyelinase.", "content": "A new type (F) of Niemann-Pick disease characterised by childhood onset of splenomegaly, lack of neurological involvement, and diminished sphingomyelinase activity is described. The clinical presentation and heat-labile sphingomyelinase activity of this type F Niemann-Pick disease distinguishes it from other types of Niemann-Pick disease.", "contents": "A new form of Niemann-Pick disease characterised by temperature-labile sphingomyelinase. A new type (F) of Niemann-Pick disease characterised by childhood onset of splenomegaly, lack of neurological involvement, and diminished sphingomyelinase activity is described. The clinical presentation and heat-labile sphingomyelinase activity of this type F Niemann-Pick disease distinguishes it from other types of Niemann-Pick disease."}
{"id": "PMID:216812", "title": "Pyridine nucleotide oxidation-reduction state of the cerebral cortex in the awake gerbil.", "content": "A new approach to study the effect of ischemia on the brain of the awake gerbil is described. The measurement of NADH fluorescence from the surface of the cortex is done by a time-sharing fluorometer/reflectometer connected to the brain via a flexible light guide and an implanted cannula. The response of the gerbil brain to anoxia and spreading depression is described. By unilateral occlusion of the carotid artery an increase in NADH was measured in the ipsilateral hemisphere.", "contents": "Pyridine nucleotide oxidation-reduction state of the cerebral cortex in the awake gerbil. A new approach to study the effect of ischemia on the brain of the awake gerbil is described. The measurement of NADH fluorescence from the surface of the cortex is done by a time-sharing fluorometer/reflectometer connected to the brain via a flexible light guide and an implanted cannula. The response of the gerbil brain to anoxia and spreading depression is described. By unilateral occlusion of the carotid artery an increase in NADH was measured in the ipsilateral hemisphere."}
{"id": "PMID:216813", "title": "Intracortical horizontal connections of neurons in cat and monkey motor cortex.", "content": "The present paper deals with the study of the structure of horizontal neuron chains, one of the aspects of intracortical intraneuronal relationships. The motor cortex (field 4) of cats and lower monkeys (Papio hamadryas and Macacus rhesus s. M. mullata) was treated by the impregnating method of Golgi--Kopsh. The drawings of neurons from 90-micrometer sections were made by means of a camera lucida. Three possible pathways of impulse transmission along neuron chains in a horizontal direction were revealed. These were: a pyramido-pyramidal system of connections which may possibly spread excitatory influence among several columns; a basket-pyramidal connection system; and connections which arise from successive switchings between neighboring neurons of one layer.", "contents": "Intracortical horizontal connections of neurons in cat and monkey motor cortex. The present paper deals with the study of the structure of horizontal neuron chains, one of the aspects of intracortical intraneuronal relationships. The motor cortex (field 4) of cats and lower monkeys (Papio hamadryas and Macacus rhesus s. M. mullata) was treated by the impregnating method of Golgi--Kopsh. The drawings of neurons from 90-micrometer sections were made by means of a camera lucida. Three possible pathways of impulse transmission along neuron chains in a horizontal direction were revealed. These were: a pyramido-pyramidal system of connections which may possibly spread excitatory influence among several columns; a basket-pyramidal connection system; and connections which arise from successive switchings between neighboring neurons of one layer."}
{"id": "PMID:216814", "title": "An x-ray microanalysis study of differences in concentration of elements in brain cells due to opiates, cell type, and subcellular location.", "content": "Adult female Sprague Dawley rats were divided into three groups and given two daily doses of: 1) morphine (25 mg/kg at each injection), or 2) methadone (5 mg/kg), or 3) saline for nine days. Two hours before the rats were killed on day 10, they were given a double dose of the drugs. Fifteen minutes before being killed, some of the morphine-treated rats were given the opiate antagonist naloxone (2.5 mg/kg), which caused a sudden arousal in these rats. At the time of killing, the preoptic-hypothalamic region was repidly removed and frozen in liquid propane to prevent translocation of elements in cells. Frozen 4-micrometer sections were cut, freeze-dried, and electron-probed in a scanning electron microscope, and energy-dispersive x-ray spectra were collected. The characteristic peak-to-continuum ratio for all detectable elements was determined in both the nucleus and the cytoplasm of ependymal cells and neurons. The data from nine cells of each type in each rat brain were then subjected to one- and three-way analysis of variance. The results show significant differences in the distribution of elements (sodium, magnesium, phosphorus, sulfur, chlorine, potassium, and calcium) which are dependent upon: 1) subcellular localization, 2) cell type, and particularly, 3) opiate treatment. The behavioral state produced by the opiates is correlated with the effects they have on intracellular concentration of several elements, most notably, sodium.", "contents": "An x-ray microanalysis study of differences in concentration of elements in brain cells due to opiates, cell type, and subcellular location. Adult female Sprague Dawley rats were divided into three groups and given two daily doses of: 1) morphine (25 mg/kg at each injection), or 2) methadone (5 mg/kg), or 3) saline for nine days. Two hours before the rats were killed on day 10, they were given a double dose of the drugs. Fifteen minutes before being killed, some of the morphine-treated rats were given the opiate antagonist naloxone (2.5 mg/kg), which caused a sudden arousal in these rats. At the time of killing, the preoptic-hypothalamic region was repidly removed and frozen in liquid propane to prevent translocation of elements in cells. Frozen 4-micrometer sections were cut, freeze-dried, and electron-probed in a scanning electron microscope, and energy-dispersive x-ray spectra were collected. The characteristic peak-to-continuum ratio for all detectable elements was determined in both the nucleus and the cytoplasm of ependymal cells and neurons. The data from nine cells of each type in each rat brain were then subjected to one- and three-way analysis of variance. The results show significant differences in the distribution of elements (sodium, magnesium, phosphorus, sulfur, chlorine, potassium, and calcium) which are dependent upon: 1) subcellular localization, 2) cell type, and particularly, 3) opiate treatment. The behavioral state produced by the opiates is correlated with the effects they have on intracellular concentration of several elements, most notably, sodium."}
{"id": "PMID:216815", "title": "Activation of brain tryptophan hydroxylase by a phosphorylating system.", "content": "A significant activation of tryptophan hydroxylase (TPH) was achieved by the addition of 1 mM ATP and 10 mM MgCl2 to 100,000g supernatant prepared from mouse midbrain. The activation produced an increase of enzyme activity by 50-70% above control. Cyclic AMP was not a necessary component in the activation as initially suspected; neither was the involvement of a cyclic AMP-dependent protein kinase detected. The enzyme activation by Mg+2-ATP was totally retained after dialysis, thus excluding the possibility of an allosteric effect. In contrast to the activation, TPH was found to be sensitive to inactivation by acid phosphatase, a dephosphorylating enzyme. These findings are consistent with the proposal that the enzyme activation may involve a phosphorylation process. Furthermore, the activation by Mg+2-ATP in the brain preparations was only minimally observed from neonatal mice and could be abolished from adult mice by administration of hydrocortisone. It appears that the phosphorylation process, as postulated here, may be under developmental and hormonal influences.", "contents": "Activation of brain tryptophan hydroxylase by a phosphorylating system. A significant activation of tryptophan hydroxylase (TPH) was achieved by the addition of 1 mM ATP and 10 mM MgCl2 to 100,000g supernatant prepared from mouse midbrain. The activation produced an increase of enzyme activity by 50-70% above control. Cyclic AMP was not a necessary component in the activation as initially suspected; neither was the involvement of a cyclic AMP-dependent protein kinase detected. The enzyme activation by Mg+2-ATP was totally retained after dialysis, thus excluding the possibility of an allosteric effect. In contrast to the activation, TPH was found to be sensitive to inactivation by acid phosphatase, a dephosphorylating enzyme. These findings are consistent with the proposal that the enzyme activation may involve a phosphorylation process. Furthermore, the activation by Mg+2-ATP in the brain preparations was only minimally observed from neonatal mice and could be abolished from adult mice by administration of hydrocortisone. It appears that the phosphorylation process, as postulated here, may be under developmental and hormonal influences."}
{"id": "PMID:216816", "title": "On potassium functional feedback in neuromuscular junction.", "content": "The dependence of the reversal potential (Erev) of intracellular end-plate potentials (epp) on activity patterns was studied in frog neuromuscular preparations. A shift of Erev to the positive side was found with change in frequency of stimulation from 1/sec to 50/sec. This shift corresponds to the increase of potassium concentration in the synaptic cleft to 7.0 mM. The effect of potassium concentration [K+]0 in the bath solution on quantal content (m) of epp was studied. The quantity m increased when [K+]0 was varied within the range 4.7-8.7 mM; m decreased when [K+]0 was greater than 8.7 mM. Such a relationship between m and [K+]0 is accounted for by the combined effect of potassium on transmitter secretion and electrogenic processes in motor nerve terminals. The correlation between the change of m with [K+]0 and initial epp amplitudes was found and was attributed to potassium efflux from post-synaptic region in varying quantity depending on the initial epp amplitudes. A scheme of synaptic self-regulation by means of potassium feedback is suggested.", "contents": "On potassium functional feedback in neuromuscular junction. The dependence of the reversal potential (Erev) of intracellular end-plate potentials (epp) on activity patterns was studied in frog neuromuscular preparations. A shift of Erev to the positive side was found with change in frequency of stimulation from 1/sec to 50/sec. This shift corresponds to the increase of potassium concentration in the synaptic cleft to 7.0 mM. The effect of potassium concentration [K+]0 in the bath solution on quantal content (m) of epp was studied. The quantity m increased when [K+]0 was varied within the range 4.7-8.7 mM; m decreased when [K+]0 was greater than 8.7 mM. Such a relationship between m and [K+]0 is accounted for by the combined effect of potassium on transmitter secretion and electrogenic processes in motor nerve terminals. The correlation between the change of m with [K+]0 and initial epp amplitudes was found and was attributed to potassium efflux from post-synaptic region in varying quantity depending on the initial epp amplitudes. A scheme of synaptic self-regulation by means of potassium feedback is suggested."}
{"id": "PMID:216817", "title": "A possible mechanism of infertility by acute cadmium intoxication.", "content": "A possible mechanism of infertility by Cd was investigated from the standpoint of influence of Cd on the contractile responses of isolated seminal vesicle from guinea pigs to K, acetylcholine, noradrenaline, Ba and Ca by using the Magnus method. Cd inhibited the contractile responses to the contractile agents tested in a dose-dependent manner. Cd showed the preferential inhibition against the contractile responses to K and Ca. The inhibitory effect of Cd on the contractile responses to noradrenaline and acetylcholine was hardly removed. The effect of Cd was inhibited by the thiol compounds, glutathione and thiola. The active mechanism of Cd was discussed in relation to Ca mobilization.", "contents": "A possible mechanism of infertility by acute cadmium intoxication. A possible mechanism of infertility by Cd was investigated from the standpoint of influence of Cd on the contractile responses of isolated seminal vesicle from guinea pigs to K, acetylcholine, noradrenaline, Ba and Ca by using the Magnus method. Cd inhibited the contractile responses to the contractile agents tested in a dose-dependent manner. Cd showed the preferential inhibition against the contractile responses to K and Ca. The inhibitory effect of Cd on the contractile responses to noradrenaline and acetylcholine was hardly removed. The effect of Cd was inhibited by the thiol compounds, glutathione and thiola. The active mechanism of Cd was discussed in relation to Ca mobilization."}
{"id": "PMID:216818", "title": "Lithium prophylaxis of corticotropin-induced psychosis.", "content": "Corticotropin is one of the few accepted treatments for acute exacerbations of multiple sclerosis and retrobulbar neuritis. Psychosis is a serious side effect usually necessitating discontinuation of the drug therapy. Because mood disorders preponderated in most patients previously described with this psychosis, 27 patients were empirically treated with lithium carbonate concurrently with corticotropin. In none of the patients treated with lithium did a psychotic reaction occur, although in a comparable group of 44 patients previously treated identically with corticotropin but without lithium, six (14%) became psychotic.", "contents": "Lithium prophylaxis of corticotropin-induced psychosis. Corticotropin is one of the few accepted treatments for acute exacerbations of multiple sclerosis and retrobulbar neuritis. Psychosis is a serious side effect usually necessitating discontinuation of the drug therapy. Because mood disorders preponderated in most patients previously described with this psychosis, 27 patients were empirically treated with lithium carbonate concurrently with corticotropin. In none of the patients treated with lithium did a psychotic reaction occur, although in a comparable group of 44 patients previously treated identically with corticotropin but without lithium, six (14%) became psychotic."}
{"id": "PMID:216819", "title": "Quality and duration of survival in glioblastoma multiforme. Combined surgical, radiation, and lomustine therapy.", "content": "A retrospective evaluation of the quality and length of survival of 74 patients nonrandomly receiving lomustine, 100 to 110 mg/sq m, following craniotomy and irradiation for glioblastoma multiforme was performed. After surgery all patients were capable of at least partial self-care. Patients receiving postoperative irradiation and lomustine had a median survival of 11.5 months. While receiving chemotherapy, 40% of these patients were capable of at least partial employment; 75% were able to care for themselves. These levels of function were stable for 70% of the average postoperative course (8.0 months), following which a decline ensued.", "contents": "Quality and duration of survival in glioblastoma multiforme. Combined surgical, radiation, and lomustine therapy. A retrospective evaluation of the quality and length of survival of 74 patients nonrandomly receiving lomustine, 100 to 110 mg/sq m, following craniotomy and irradiation for glioblastoma multiforme was performed. After surgery all patients were capable of at least partial self-care. Patients receiving postoperative irradiation and lomustine had a median survival of 11.5 months. While receiving chemotherapy, 40% of these patients were capable of at least partial employment; 75% were able to care for themselves. These levels of function were stable for 70% of the average postoperative course (8.0 months), following which a decline ensued."}
{"id": "PMID:216821", "title": "Metyrapone test with adrenocorticotrophic levels. Separating primary from secondary adrenal insufficiency.", "content": "Basal plasma adrenocorticotrophic hormone (ACTH) and cortisol concentrations as well as plasma ACTH and 11-deoxycortisol responses to the administration of a single dose of metyrapone were evaluated in 104 patients with intact pituitary-adrenal axis, in 20 patients with secondary adrenal insufficiency, and in seven patients with primary adrenal insufficiency. In patients with primary adrenal insufficiency, baseline ACTH levels were high. Following metyrapone administration, 11-deoxycortisol concentrations were low and ACTH levels did not change. In patients with secondary adrenal insufficiency, baseline plasma ACTH levels were normal, but neither 11-deoxycortisol nor ACTH levels increased in response to metyrapone. The metyrapone test is not only useful to screen for adrenal insufficiency, it is also useful to differentiate a primary from a secondary cause.", "contents": "Metyrapone test with adrenocorticotrophic levels. Separating primary from secondary adrenal insufficiency. Basal plasma adrenocorticotrophic hormone (ACTH) and cortisol concentrations as well as plasma ACTH and 11-deoxycortisol responses to the administration of a single dose of metyrapone were evaluated in 104 patients with intact pituitary-adrenal axis, in 20 patients with secondary adrenal insufficiency, and in seven patients with primary adrenal insufficiency. In patients with primary adrenal insufficiency, baseline ACTH levels were high. Following metyrapone administration, 11-deoxycortisol concentrations were low and ACTH levels did not change. In patients with secondary adrenal insufficiency, baseline plasma ACTH levels were normal, but neither 11-deoxycortisol nor ACTH levels increased in response to metyrapone. The metyrapone test is not only useful to screen for adrenal insufficiency, it is also useful to differentiate a primary from a secondary cause."}
{"id": "PMID:216831", "title": "Epstein-Barr virus antibodies in Sudanese patients with nasopharyngeal carcinoma: a preliminary report.", "content": "With the use of an immunofluorescence technique Epstein-Barr viral capsid antigen antibody titers were determined in the sera from 226 Sudanese: 41 with nasopharyngeal carcinoma (NPC), 77 with other head and neck cancers, 21 with malignant lymphomas, 63 with other cancers, 6 with specific granulomas, and 18 normal controls. Of the NPC patients, 87.8% had titers of 320 or greater and 43.9% had titers of 2,560 or more, whereas none had titers of less than 40. Their geometric mean titer (GMT) level was 1,855. However, compared to the NPC patients, the other patients and normal controls showed significantly higher percentages of sera with low titers and lower percentages of sera with high titers and they had a GMT that was 4--16 times lower. The high NPC titers were independent of age, sex, tribe, or locality of patients. The preliminary results indicated the importance of future immunovirologic and immunogenetic field investigations on the natural history of the Epstein-Barr virus and on the genetics of the host.", "contents": "Epstein-Barr virus antibodies in Sudanese patients with nasopharyngeal carcinoma: a preliminary report. With the use of an immunofluorescence technique Epstein-Barr viral capsid antigen antibody titers were determined in the sera from 226 Sudanese: 41 with nasopharyngeal carcinoma (NPC), 77 with other head and neck cancers, 21 with malignant lymphomas, 63 with other cancers, 6 with specific granulomas, and 18 normal controls. Of the NPC patients, 87.8% had titers of 320 or greater and 43.9% had titers of 2,560 or more, whereas none had titers of less than 40. Their geometric mean titer (GMT) level was 1,855. However, compared to the NPC patients, the other patients and normal controls showed significantly higher percentages of sera with low titers and lower percentages of sera with high titers and they had a GMT that was 4--16 times lower. The high NPC titers were independent of age, sex, tribe, or locality of patients. The preliminary results indicated the importance of future immunovirologic and immunogenetic field investigations on the natural history of the Epstein-Barr virus and on the genetics of the host."}
{"id": "PMID:216832", "title": "Surface glycopeptide change triggered by contact between normal cells from rat liver and their simian virus 40-transformed cells from the same virus.", "content": "Surface glycopeptide changes triggered by mixed culture of normal cells from rat liver cell line WIRL-3 and simian virus 40-transformed cells from the same line were studied. In addition, biologic responses of the normal cells and the transformed cells to three kinds of surface glycopeptides derived from the normal cells, the transformed cells, and these cells in mixed culture were investigated. Surface glycopeptide derived from the mixed culture showed a quantitative increase and a qualitative change in the glycopeptide structure, not detected in the surface glycopeptide of normal cells and transformed cells cultured separately. The surface glycopeptide changes observed in the mixed culture were mainly ascribable to normal cells responding to transformed cells, and a surface glycopeptide change in normal cells induced a qualitative surface glycopeptide change in transformed cells. Differences in biologic response of normal cells and transformed cells to the above three surface glycopeptides were investigated with the use of inhibition of [3H]thymidine uptake of the cells by the three different surface glycopeptide preparations. The inhibition rates of uptake in normal cells were 30% by all three surface glycopeptides (200 microgram/ml culture medium); inhibition rates in transformed cells were 65% by mixed-culture surface glycopeptide, 50% by normal cell-surface glycopeptide, and 35% by transformed cell-surface glycopeptide.", "contents": "Surface glycopeptide change triggered by contact between normal cells from rat liver and their simian virus 40-transformed cells from the same virus. Surface glycopeptide changes triggered by mixed culture of normal cells from rat liver cell line WIRL-3 and simian virus 40-transformed cells from the same line were studied. In addition, biologic responses of the normal cells and the transformed cells to three kinds of surface glycopeptides derived from the normal cells, the transformed cells, and these cells in mixed culture were investigated. Surface glycopeptide derived from the mixed culture showed a quantitative increase and a qualitative change in the glycopeptide structure, not detected in the surface glycopeptide of normal cells and transformed cells cultured separately. The surface glycopeptide changes observed in the mixed culture were mainly ascribable to normal cells responding to transformed cells, and a surface glycopeptide change in normal cells induced a qualitative surface glycopeptide change in transformed cells. Differences in biologic response of normal cells and transformed cells to the above three surface glycopeptides were investigated with the use of inhibition of [3H]thymidine uptake of the cells by the three different surface glycopeptide preparations. The inhibition rates of uptake in normal cells were 30% by all three surface glycopeptides (200 microgram/ml culture medium); inhibition rates in transformed cells were 65% by mixed-culture surface glycopeptide, 50% by normal cell-surface glycopeptide, and 35% by transformed cell-surface glycopeptide."}
{"id": "PMID:216833", "title": "Enhanced oncornavirus expression in Marek's disease tumors from specific-pathogen-free chickens.", "content": "An oncornavirus was recovered from cell cultures of kidney tumors from specific-pathogen-free chickens inoculated with Marek's disease herpesvirus (MDHV). The MDHV inoculum was free of infectious avian leukosis virus (ALV). Direct examination of a variety of tissues from MDHV-inoculated chickens demonstrated increased levels of ALV-specific RNA compared to tissues from diluent-inoculated (control) chickens. DNA from cultured kidney tumor cells annealed to an ALV complementary DNA probe at the same rate and exhibited the same extent of homology as DNA from cultured control kidney cells. This finding indicated the absence of exogenous ALV proviral sequences. As with vertically transmitted endogenous ALV of subgroup E, the oncornavirus recovered from kidney tumor cell cultures failed to replicate in chicken embryo fibroblast (CEF) cultures of the C/E phenotype, but did replicate in turkey embryo fibroblasts (TEF), which are permissive for replication of endogenous ALV of subgroup E. These oncornavirus particles served as a helper virus to form Rous sarcoma virus pseudotypes, which produced foci in TEF cultures but not in CEF cultures of the C/E phenotype. Whether enhanced expression of endogenous oncornavirus contributes to MDHV-induced tumorigenesis is not known.", "contents": "Enhanced oncornavirus expression in Marek's disease tumors from specific-pathogen-free chickens. An oncornavirus was recovered from cell cultures of kidney tumors from specific-pathogen-free chickens inoculated with Marek's disease herpesvirus (MDHV). The MDHV inoculum was free of infectious avian leukosis virus (ALV). Direct examination of a variety of tissues from MDHV-inoculated chickens demonstrated increased levels of ALV-specific RNA compared to tissues from diluent-inoculated (control) chickens. DNA from cultured kidney tumor cells annealed to an ALV complementary DNA probe at the same rate and exhibited the same extent of homology as DNA from cultured control kidney cells. This finding indicated the absence of exogenous ALV proviral sequences. As with vertically transmitted endogenous ALV of subgroup E, the oncornavirus recovered from kidney tumor cell cultures failed to replicate in chicken embryo fibroblast (CEF) cultures of the C/E phenotype, but did replicate in turkey embryo fibroblasts (TEF), which are permissive for replication of endogenous ALV of subgroup E. These oncornavirus particles served as a helper virus to form Rous sarcoma virus pseudotypes, which produced foci in TEF cultures but not in CEF cultures of the C/E phenotype. Whether enhanced expression of endogenous oncornavirus contributes to MDHV-induced tumorigenesis is not known."}
{"id": "PMID:216834", "title": "Radiation induction of endogenous type C virus from mouse cells transformed in vitro by murine sarcoma virus.", "content": "Cell lines from AKR and BALB/c mouse embryos were compared for their sensitivity to X-ray induction of endogenous type C virus. K-Balb cells, a Balb/3T3 cell line nonproductively transformed by Kirsten murine sarcoma virus, were found to be sensitive to X-irradiation. At a dose as low as 50 R, X-rays induced virus expression in K-Balb cells, and the induction frequency increased with increasing dose of X-rays up to 400 R. Among two classes of inducible endogenous viruses carried by K-Balb cells, only Balb:virus-2 was activated by X-irradiation, whereas both Balb:virus-1 and Balb:virus-2 were activated after the cells were treated with 5-iodo-2'-deoxyuridine. UV light and 4-nitroquinoline 1-oxide were also shown to induce virus expression in K-Balb cells. The virus-induction frequency for these physical and chemical carcinogens was much lower (approximately 3 times 10(-4)) than that for 5-bromo-2'-deoxyuridine (approximately 1 times 10(-1)).", "contents": "Radiation induction of endogenous type C virus from mouse cells transformed in vitro by murine sarcoma virus. Cell lines from AKR and BALB/c mouse embryos were compared for their sensitivity to X-ray induction of endogenous type C virus. K-Balb cells, a Balb/3T3 cell line nonproductively transformed by Kirsten murine sarcoma virus, were found to be sensitive to X-irradiation. At a dose as low as 50 R, X-rays induced virus expression in K-Balb cells, and the induction frequency increased with increasing dose of X-rays up to 400 R. Among two classes of inducible endogenous viruses carried by K-Balb cells, only Balb:virus-2 was activated by X-irradiation, whereas both Balb:virus-1 and Balb:virus-2 were activated after the cells were treated with 5-iodo-2'-deoxyuridine. UV light and 4-nitroquinoline 1-oxide were also shown to induce virus expression in K-Balb cells. The virus-induction frequency for these physical and chemical carcinogens was much lower (approximately 3 times 10(-4)) than that for 5-bromo-2'-deoxyuridine (approximately 1 times 10(-1))."}
{"id": "PMID:216835", "title": "Phenotypically distinct target cells for murine sarcoma virus and murine leukemia virus marrow transformation in vitro.", "content": "An in vitro hematopoietic microenvironment was established from explained fragments of bone marrow from adult noninbred NIH Swiss mice with the use of corticosteroid-reconstituted horse serum. Infection with Kirsten murine sarcoma virus (Ki-MuSV) with either a Rauscher murine leukemia virus (R-MuLV) or Balb:virus-1 helper virus coat reduced proliferation of granulocytic and pluripotent hematopoietic stem cells and produced neoplastic transformation of both macrophages and preadipocytes in the adherent cell population within a 4-week period. Ki-MuSV-transformed, virus-releasing macrophages formed clusters of 4-49 cells in 0.8% methylcellulose-containing medium in the absence of added colony-stimulating factor (CSF), synthesized lysozyme, ASD-chloroacetate substrate-specific esterase-M, and CSF, and produced tumors following inoculation iv into adult NIH Swiss mice or ip into newborn NIH Swiss mice. In cultures infected with helper leukemia viruses R-MuLV or Balb:virus-1, gradual transformation of a distinct cell phenotype was observed over a 9-week period with generation of increasing numbers of atypical myeloblasts and promyelocytes which showed dyssynchronous nuclear-cytoplasmic maturation, basophilic granulation, cytoplasmic vacuolation, and formation of incompletely maturing CSF-dependent granulocyte-macrophage colonies in vitro and small spleen colonies in vivo. These data demonstrated that rapid biologic expression of the murine sarcoma virus genome in specific adherent \"stromal\" marrow cells prevents detection of a more subtle helper-virus-induced dysmyelopoiesis in a distinct nonadherent cell population.", "contents": "Phenotypically distinct target cells for murine sarcoma virus and murine leukemia virus marrow transformation in vitro. An in vitro hematopoietic microenvironment was established from explained fragments of bone marrow from adult noninbred NIH Swiss mice with the use of corticosteroid-reconstituted horse serum. Infection with Kirsten murine sarcoma virus (Ki-MuSV) with either a Rauscher murine leukemia virus (R-MuLV) or Balb:virus-1 helper virus coat reduced proliferation of granulocytic and pluripotent hematopoietic stem cells and produced neoplastic transformation of both macrophages and preadipocytes in the adherent cell population within a 4-week period. Ki-MuSV-transformed, virus-releasing macrophages formed clusters of 4-49 cells in 0.8% methylcellulose-containing medium in the absence of added colony-stimulating factor (CSF), synthesized lysozyme, ASD-chloroacetate substrate-specific esterase-M, and CSF, and produced tumors following inoculation iv into adult NIH Swiss mice or ip into newborn NIH Swiss mice. In cultures infected with helper leukemia viruses R-MuLV or Balb:virus-1, gradual transformation of a distinct cell phenotype was observed over a 9-week period with generation of increasing numbers of atypical myeloblasts and promyelocytes which showed dyssynchronous nuclear-cytoplasmic maturation, basophilic granulation, cytoplasmic vacuolation, and formation of incompletely maturing CSF-dependent granulocyte-macrophage colonies in vitro and small spleen colonies in vivo. These data demonstrated that rapid biologic expression of the murine sarcoma virus genome in specific adherent \"stromal\" marrow cells prevents detection of a more subtle helper-virus-induced dysmyelopoiesis in a distinct nonadherent cell population."}
{"id": "PMID:216836", "title": "Avian oncovirus Mill Hill No. 2: pathogenicity in chickens.", "content": "Mill Hill No. 2 (MH2), an avian tumor virus, was studied for its transforming and oncogenic effects. In tissue culture it induced transformation of chicken fibroblasts and yolk sac macrophages. When injected into the chicken, the main feature of this virus was its ability to cause liver and kidney carcinoma, in addition to sarcoma. MH2-associated viruses did not transform cell cultures but were able to cause only lymphoma in the birds. Light and electron microscopy were used in a detailed histologic study of the tumors induced by MH2 virus. An unclassified round cell sarcoma was produced in soft tissues at sites of injection; there was no evidence of origin from endothelium. In the kidney, carcinomas mixed with a malignant stroma were found. Hepatocarcinomas were the dominant tumors found in the liver. The lymphomas produced by the associated virus were poorly differentiated and highly malignant. The study illustrated the highly oncogenic potential of this virus and offered a model for the analysis of the carcinogenic events in a more specific way.", "contents": "Avian oncovirus Mill Hill No. 2: pathogenicity in chickens. Mill Hill No. 2 (MH2), an avian tumor virus, was studied for its transforming and oncogenic effects. In tissue culture it induced transformation of chicken fibroblasts and yolk sac macrophages. When injected into the chicken, the main feature of this virus was its ability to cause liver and kidney carcinoma, in addition to sarcoma. MH2-associated viruses did not transform cell cultures but were able to cause only lymphoma in the birds. Light and electron microscopy were used in a detailed histologic study of the tumors induced by MH2 virus. An unclassified round cell sarcoma was produced in soft tissues at sites of injection; there was no evidence of origin from endothelium. In the kidney, carcinomas mixed with a malignant stroma were found. Hepatocarcinomas were the dominant tumors found in the liver. The lymphomas produced by the associated virus were poorly differentiated and highly malignant. The study illustrated the highly oncogenic potential of this virus and offered a model for the analysis of the carcinogenic events in a more specific way."}
{"id": "PMID:216837", "title": "Infectivity tests of secretions and excretions from cattle infected with bovine leukemia virus.", "content": "Secretions and excretions from cattle with persistent bovine leukemia virus (BLV) infections were tested for BLV by inoculation into sheep. Development of antibody to the BLV glycoprotein antigen and reisolation of virus from peripheral blood leukocytes were the two criteria used to confirm infection in test sheep. The virus was detected in milk from 4 of 6 cows examined and in colostrum from 1 of 4 cows examined. The virus was not detected in semen from 8 bulls or in nasal secretions, saliva, and urine from 2 cows.", "contents": "Infectivity tests of secretions and excretions from cattle infected with bovine leukemia virus. Secretions and excretions from cattle with persistent bovine leukemia virus (BLV) infections were tested for BLV by inoculation into sheep. Development of antibody to the BLV glycoprotein antigen and reisolation of virus from peripheral blood leukocytes were the two criteria used to confirm infection in test sheep. The virus was detected in milk from 4 of 6 cows examined and in colostrum from 1 of 4 cows examined. The virus was not detected in semen from 8 bulls or in nasal secretions, saliva, and urine from 2 cows."}
{"id": "PMID:216838", "title": "Human brain tumor transplantation into nude mice.", "content": "Seven human brain tumors were transplanted into the brains (6/7 takes) and subcutaneous tissues (7/7 takes) of athymic nude mice. Compared to experimental animal brain tumors, these tumors, taken directly from patients in the operating room and transplanted, grew more slowly in the mice; their growth rates following explant generally paralleled those in the patients. A rough correlation was seen between the degree of the tumor's malignancy and both successful take and rate of growth following explant. The tumors' growth rates increased during serial transplantation after explant. Two tumors developed into long-term serial lines; both came from gliosarcomas. Preliminary chemotherapy experiments with these two lines demonstrated different chemosensitivities. One line was very sensitive to the nitrosoureas and resistant to procarbazine; the other line was more sensitive to procarbazine than to the nitrosoureas. This model permits study of the biologic behavior of human brain tumors growing intracerebrally and subcutaneously in nude mice.", "contents": "Human brain tumor transplantation into nude mice. Seven human brain tumors were transplanted into the brains (6/7 takes) and subcutaneous tissues (7/7 takes) of athymic nude mice. Compared to experimental animal brain tumors, these tumors, taken directly from patients in the operating room and transplanted, grew more slowly in the mice; their growth rates following explant generally paralleled those in the patients. A rough correlation was seen between the degree of the tumor's malignancy and both successful take and rate of growth following explant. The tumors' growth rates increased during serial transplantation after explant. Two tumors developed into long-term serial lines; both came from gliosarcomas. Preliminary chemotherapy experiments with these two lines demonstrated different chemosensitivities. One line was very sensitive to the nitrosoureas and resistant to procarbazine; the other line was more sensitive to procarbazine than to the nitrosoureas. This model permits study of the biologic behavior of human brain tumors growing intracerebrally and subcutaneously in nude mice."}
{"id": "PMID:216839", "title": "GFA and S 100 protein levels as an index for malignancy in human gliomas and neurinomas.", "content": "Human glia-specific proteins S 100 and GFA were quantitated by use of a rocket immunoelectrophoresis technique with monospecific antisera. No relation was found between the S 100 protein content of an astrocytoma and its degree of neoplasia. However, the lower the GFA protein content of the astrocytoma, the more malignant it was. Similarly, the more malignant a neurinoma was, the lower was its S 100 protein content. Therefore, the levels of these proteins might be used as indexes of neoplastic dedifferentiation.", "contents": "GFA and S 100 protein levels as an index for malignancy in human gliomas and neurinomas. Human glia-specific proteins S 100 and GFA were quantitated by use of a rocket immunoelectrophoresis technique with monospecific antisera. No relation was found between the S 100 protein content of an astrocytoma and its degree of neoplasia. However, the lower the GFA protein content of the astrocytoma, the more malignant it was. Similarly, the more malignant a neurinoma was, the lower was its S 100 protein content. Therefore, the levels of these proteins might be used as indexes of neoplastic dedifferentiation."}
{"id": "PMID:216840", "title": "Immunohistologic evaluation of the lymphoreticular infiltrate of human central nervous system tumors.", "content": "Forty-five nervous system tumors (9 glioblastomas, 9 meningiomas, 15 assorted primary neural tumors including 3 medulloblastomas, and 12 brain tumors metastatic to the brain were analyzed for their content of lymphocytes, granulocytes, and macrophages. Cell suspensions were prepared by enzymatic digestion; lymphocytes and granulocytes were quantitated by morphology following cytocentrifugation, and macrophages were quantitated by IgG EAC (erythrocyte-antibody-complement) rosette formation. EA (erythrocyte-antibody) adsorption to sections of tumor was employed to determine the distribution of the IgG Fc receptor-positive cells within the tumors and to serve as quality control for selective release of Fc receptor-positive cells by enzyme digestion. The 9 glioblastomas had a mean macrophage content of 41% (range: 5-78%); the 9 meningiomas, 42% (range: 5-80%); the 3 medulloblastomas, 6% (range: 2-15%); and the metastatic tumors, 21% (range: 2-50%). Lymphocyte contents were variable but generally less than 10%. Most tumors contained less than 10% granulocytes. EA adsorption demonstrated that Fc receptor-positive cells were distributed throughout the tumor mass, although different types of patterns were observed. There was an excellent correlation between the percent EAC rosette-positive cells in suspensions and the extent of EA adsorption to the tumor sections. The significance of the study primarily rests in the demonstration that most nervous system tumors contain high numbers of infiltrating host cells, primarily macrophages.", "contents": "Immunohistologic evaluation of the lymphoreticular infiltrate of human central nervous system tumors. Forty-five nervous system tumors (9 glioblastomas, 9 meningiomas, 15 assorted primary neural tumors including 3 medulloblastomas, and 12 brain tumors metastatic to the brain were analyzed for their content of lymphocytes, granulocytes, and macrophages. Cell suspensions were prepared by enzymatic digestion; lymphocytes and granulocytes were quantitated by morphology following cytocentrifugation, and macrophages were quantitated by IgG EAC (erythrocyte-antibody-complement) rosette formation. EA (erythrocyte-antibody) adsorption to sections of tumor was employed to determine the distribution of the IgG Fc receptor-positive cells within the tumors and to serve as quality control for selective release of Fc receptor-positive cells by enzyme digestion. The 9 glioblastomas had a mean macrophage content of 41% (range: 5-78%); the 9 meningiomas, 42% (range: 5-80%); the 3 medulloblastomas, 6% (range: 2-15%); and the metastatic tumors, 21% (range: 2-50%). Lymphocyte contents were variable but generally less than 10%. Most tumors contained less than 10% granulocytes. EA adsorption demonstrated that Fc receptor-positive cells were distributed throughout the tumor mass, although different types of patterns were observed. There was an excellent correlation between the percent EAC rosette-positive cells in suspensions and the extent of EA adsorption to the tumor sections. The significance of the study primarily rests in the demonstration that most nervous system tumors contain high numbers of infiltrating host cells, primarily macrophages."}
{"id": "PMID:216841", "title": "Effects of subcutaneous administration of chemical carcinogens on leukemia in C58 mice.", "content": "The effects of sc administration of 3-methylcholanthrene (MCA), 7,12-dimethylbenz[a]anthracene (DMBA), and benzo[a]pyrene (BP) on spontaneous viral leukemia and subcutaneous sarcoma induction have been studied in weanling C58/J mice. MCA produced significantly more sarcomas at the inoculation site than did DMBA or BP; moreover, it interfered with leukemia development. DMBA produced fewer sarcomas, and the incidence of leukemia was comparable to that found in the controls. BP accelerated the incidence of leukemia, although no sarcomas were produced. When the effect of the age of the mice at the time of MCA treatment on the incidence of leukemia and sarcomas was studied, newborn and weanling mice were found to develop primarily sarcomas, whereas no sarcomas were produced in the 16-week-old mice, and 52-64% of the 16-week-old mice developed leukemia. The reason no sarcomas were found in the C58 mice was apparently different from the reason no sarcomas were found in AKR mice, inasmuch as the AKR mice did not live long enough for sarcomas to develop. Immunologic surveillance may have played a part in the sarcoma suppression in the C58 mouse.", "contents": "Effects of subcutaneous administration of chemical carcinogens on leukemia in C58 mice. The effects of sc administration of 3-methylcholanthrene (MCA), 7,12-dimethylbenz[a]anthracene (DMBA), and benzo[a]pyrene (BP) on spontaneous viral leukemia and subcutaneous sarcoma induction have been studied in weanling C58/J mice. MCA produced significantly more sarcomas at the inoculation site than did DMBA or BP; moreover, it interfered with leukemia development. DMBA produced fewer sarcomas, and the incidence of leukemia was comparable to that found in the controls. BP accelerated the incidence of leukemia, although no sarcomas were produced. When the effect of the age of the mice at the time of MCA treatment on the incidence of leukemia and sarcomas was studied, newborn and weanling mice were found to develop primarily sarcomas, whereas no sarcomas were produced in the 16-week-old mice, and 52-64% of the 16-week-old mice developed leukemia. The reason no sarcomas were found in the C58 mice was apparently different from the reason no sarcomas were found in AKR mice, inasmuch as the AKR mice did not live long enough for sarcomas to develop. Immunologic surveillance may have played a part in the sarcoma suppression in the C58 mouse."}
{"id": "PMID:216842", "title": "Trisomy no. 15 in murine thymomas induced by chemical carcinogens, X-irradiation, and an endogenous murine leukemia virus.", "content": "Chromosome banding techniques were used to examine the karyotype of tumor cells from thymic lymphomas induced by three different carcinogens (X-irradiation, polycyclic aromatic hydrocarbons, and an endogenous leukemogenic virus) after injection into neonatal mice of 2 different inbred mouse strains (CFW/D and C57BL/Ka). A total of 89 tumors were studied, and of these 85.4% were characterized by a modal chromosome number of 41. The additional chromosome was the result of a specific abnormality identified as trisomy of chromosome no. 15. The results obtained were independent of the carcinogenic agents and the strain of mouse used. Of the 13 tumors found to have a normal chromosome complement, 4 were induced by X-irradiation and the remaining 9 by the chemical carcinogens. All 15 virus-induced tumors analyzed had a modal chromosome number of 41.", "contents": "Trisomy no. 15 in murine thymomas induced by chemical carcinogens, X-irradiation, and an endogenous murine leukemia virus. Chromosome banding techniques were used to examine the karyotype of tumor cells from thymic lymphomas induced by three different carcinogens (X-irradiation, polycyclic aromatic hydrocarbons, and an endogenous leukemogenic virus) after injection into neonatal mice of 2 different inbred mouse strains (CFW/D and C57BL/Ka). A total of 89 tumors were studied, and of these 85.4% were characterized by a modal chromosome number of 41. The additional chromosome was the result of a specific abnormality identified as trisomy of chromosome no. 15. The results obtained were independent of the carcinogenic agents and the strain of mouse used. Of the 13 tumors found to have a normal chromosome complement, 4 were induced by X-irradiation and the remaining 9 by the chemical carcinogens. All 15 virus-induced tumors analyzed had a modal chromosome number of 41."}
{"id": "PMID:216843", "title": "Lipoprotein X and alkaline phosphatase as indicators of cholestasis.", "content": "Lipoprotein X is considered to be an indicator of cholestasis, but its clinical usefulness is unclear owing to different methods of measurement in use and varying definitions of cholestasis. We investigated the reliability of the qualitative determination of lipoprotein X in predicting cholestasis, defined here as the presence of stainable bile in tissue sections. Liver tissue and serum were collected from 42 patients. Patients were divided into those who did and those who did not have stainable bile in tissue sections. Lipoprotein X was demonstrated by electrophoresis and polyanion precipitation. Lipoprotein X in serum correlated with the presence of stainable bile (p = 0.0006). A normal range of alkaline phosphatase values correlated with the absence (p = 0.04), but elevated values did not correlate with the presence of stainable bile. In patients known to have elevated alkaline phosphatase, the presence of lipoprotein X still correlated with the presence of bile (p = 0.008). We conclude that lipoprotein X is a reliable indicator of cholestasis and that it is more useful than alkaline phosphatase in this application.", "contents": "Lipoprotein X and alkaline phosphatase as indicators of cholestasis. Lipoprotein X is considered to be an indicator of cholestasis, but its clinical usefulness is unclear owing to different methods of measurement in use and varying definitions of cholestasis. We investigated the reliability of the qualitative determination of lipoprotein X in predicting cholestasis, defined here as the presence of stainable bile in tissue sections. Liver tissue and serum were collected from 42 patients. Patients were divided into those who did and those who did not have stainable bile in tissue sections. Lipoprotein X was demonstrated by electrophoresis and polyanion precipitation. Lipoprotein X in serum correlated with the presence of stainable bile (p = 0.0006). A normal range of alkaline phosphatase values correlated with the absence (p = 0.04), but elevated values did not correlate with the presence of stainable bile. In patients known to have elevated alkaline phosphatase, the presence of lipoprotein X still correlated with the presence of bile (p = 0.008). We conclude that lipoprotein X is a reliable indicator of cholestasis and that it is more useful than alkaline phosphatase in this application."}
{"id": "PMID:216846", "title": "[Tangier-disease (author's transl)].", "content": "Tangier disease is a rare autosomal recessive lipid transport disease characterized by the absence of the usual high density lipoproteins from plasma and cholesteryl ester storage in many organs. 25 cases of Tangier disease have been described so long. The predominant clinical symptoms include tonsilar hypertrophy, splenomegaly and peripheral neuropathy. The cholesteryl ester storage is limited to macrophages, Schwann's cells and intestinal smooth muscle cells. Hypocholest erolemia (less than 80mg/dl), hypertriglyceridemia (greater than 200 mg/dl), and the absence of high density lipoproteins in agarose electrophoresis are the major plasma abnormalities. The protein moiety of normal high density lipoprotein consists of apoprotein A-I and apoprotein A-II. In Tangier disease, serum concentrations of these apoproteins are reduced to less than 1% and 5-10%, respectively. Theories concerning the pathogenesis of Tangier disease are only incomplete and unproved up to now; however, a structural abnormality of apoprotein A-I causing an inability to  bind to lipid or other proteins (apoprotein A-II) is consistent with several of the recent biochemical findings. The imbalance of cellular cholesterol metabolism caused by the absence of high density lipoproteins as well as the presumed role of these lipoproteins in cholesterol removal from cells are discussed in this article.", "contents": "[Tangier-disease (author's transl)]. Tangier disease is a rare autosomal recessive lipid transport disease characterized by the absence of the usual high density lipoproteins from plasma and cholesteryl ester storage in many organs. 25 cases of Tangier disease have been described so long. The predominant clinical symptoms include tonsilar hypertrophy, splenomegaly and peripheral neuropathy. The cholesteryl ester storage is limited to macrophages, Schwann's cells and intestinal smooth muscle cells. Hypocholest erolemia (less than 80mg/dl), hypertriglyceridemia (greater than 200 mg/dl), and the absence of high density lipoproteins in agarose electrophoresis are the major plasma abnormalities. The protein moiety of normal high density lipoprotein consists of apoprotein A-I and apoprotein A-II. In Tangier disease, serum concentrations of these apoproteins are reduced to less than 1% and 5-10%, respectively. Theories concerning the pathogenesis of Tangier disease are only incomplete and unproved up to now; however, a structural abnormality of apoprotein A-I causing an inability to  bind to lipid or other proteins (apoprotein A-II) is consistent with several of the recent biochemical findings. The imbalance of cellular cholesterol metabolism caused by the absence of high density lipoproteins as well as the presumed role of these lipoproteins in cholesterol removal from cells are discussed in this article."}
{"id": "PMID:216851", "title": "Intracellular collagen fibrils in human sarcomas.", "content": "Intracellular collagen was detected by electron microscopy in 14 sarcomas including six osteogenic sarcomas, three liposarcomas, three malignant fibrous histiocytomas, one pleomorphic rhabdomyosarcoma, and one childhood rhabdomyosarcoma. It was contained in not only the fibroblastic cells, but also in the osteoblastic, lipoblastic, myofibroblastic, and primitive cells of the various tumors. The banded intracellular collagen fibrils were observed in large phagocytic vesicles and in smaller membrane-bound vesicles which also appeared to fuse with lysosomes. Residual banding could be seen as well in many such phagolysosomes. Banded collagen was also noted in a primary explant in tissue culture. These findings suggest that the configurations of intracellular collagen seen, are parts of a continuum of a secondary pathway of collagen degradation in mesenchymal tissue and that pathway is one factor indicating a close interrelationship between these sarcomas.", "contents": "Intracellular collagen fibrils in human sarcomas. Intracellular collagen was detected by electron microscopy in 14 sarcomas including six osteogenic sarcomas, three liposarcomas, three malignant fibrous histiocytomas, one pleomorphic rhabdomyosarcoma, and one childhood rhabdomyosarcoma. It was contained in not only the fibroblastic cells, but also in the osteoblastic, lipoblastic, myofibroblastic, and primitive cells of the various tumors. The banded intracellular collagen fibrils were observed in large phagocytic vesicles and in smaller membrane-bound vesicles which also appeared to fuse with lysosomes. Residual banding could be seen as well in many such phagolysosomes. Banded collagen was also noted in a primary explant in tissue culture. These findings suggest that the configurations of intracellular collagen seen, are parts of a continuum of a secondary pathway of collagen degradation in mesenchymal tissue and that pathway is one factor indicating a close interrelationship between these sarcomas."}
{"id": "PMID:216853", "title": "Impact of aftercare in the treatment of alcoholics: a cross-lagged panel analysis.", "content": "Participation in aftercare activities during the first 3 months following discharge from inpatient treatment had a positive effect on outcome at 3 months and 6 months, but participation decreased between 3 and 6 months as patients who were doing best began to drop out of the aftercare system.", "contents": "Impact of aftercare in the treatment of alcoholics: a cross-lagged panel analysis. Participation in aftercare activities during the first 3 months following discharge from inpatient treatment had a positive effect on outcome at 3 months and 6 months, but participation decreased between 3 and 6 months as patients who were doing best began to drop out of the aftercare system."}
{"id": "PMID:216854", "title": "Selective surgical resection in small cell carcinoma of the lung.", "content": "Surgical resection has failed notably as definitive treatment for small cell carcinoma of the lung. Newer treatment programs combining intensive chemotherapy with radiation therapy achieve a significant response in about 85 percent of cases, with about 50 percent of patients showing clinically complete remission. Long-term survival without recurrence has been the outcome in a small minority of cases. A frequent mode of failure after treatment of limited disease is recurrence within the chest. The course of one patient treated early in this series suggests that exclusion of initial surgical resection from programs of combined treatment may be a serious omission. Since that time, four patients have undergone initial resection, apparently with uniformly favorable courses to date. Selection criteria based on staging factors are proposed. Admittedly, only a minority of patients will be suitable for this treatment at the time of first diagnosis. Much opportunity exists for improvement in survival rates of patients, even those with limited disease.", "contents": "Selective surgical resection in small cell carcinoma of the lung. Surgical resection has failed notably as definitive treatment for small cell carcinoma of the lung. Newer treatment programs combining intensive chemotherapy with radiation therapy achieve a significant response in about 85 percent of cases, with about 50 percent of patients showing clinically complete remission. Long-term survival without recurrence has been the outcome in a small minority of cases. A frequent mode of failure after treatment of limited disease is recurrence within the chest. The course of one patient treated early in this series suggests that exclusion of initial surgical resection from programs of combined treatment may be a serious omission. Since that time, four patients have undergone initial resection, apparently with uniformly favorable courses to date. Selection criteria based on staging factors are proposed. Admittedly, only a minority of patients will be suitable for this treatment at the time of first diagnosis. Much opportunity exists for improvement in survival rates of patients, even those with limited disease."}
{"id": "PMID:216855", "title": "Evaluation of sternal bone marrow aspiration for detection of tumor cells in patients with bronchogenic carcinoma.", "content": "We evaluated sternal bone marrow aspiration as a routine pretreatment procedure in patients with bronchogenic carcinoma. The overall rate of identification of tumor cells by this technique was found to be low. When oat cell bronchogenic carcinoma was considered as a separate entity, the positive rate was higher. However, in no instance did the bone marrow aspiration result in a change in clinical staging.", "contents": "Evaluation of sternal bone marrow aspiration for detection of tumor cells in patients with bronchogenic carcinoma. We evaluated sternal bone marrow aspiration as a routine pretreatment procedure in patients with bronchogenic carcinoma. The overall rate of identification of tumor cells by this technique was found to be low. When oat cell bronchogenic carcinoma was considered as a separate entity, the positive rate was higher. However, in no instance did the bone marrow aspiration result in a change in clinical staging."}
{"id": "PMID:216857", "title": "Vascular relaxation, aging and thyroid hormones.", "content": "Previous work indicates vascular can be studied in vitro and that there is a marked age-associated decrease in the ability of rat aortic strips to relax in response to beta-adrenergic agonists. The present studies were aimed at better understanding the role of thyroid hormones in vascular relaxation and aging. Removal of the thyroid gland from young rats resulted in a decrease in the ability of isoproterenol to relax the aorta. Relaxation caused by nitroglycerin, a non-specific relaxant, was not impaired by thyroidectomy. In 22-month-old rats, isoproterenol caused no relaxation unless exogenous thyroid hormones were administered. Hypophysectomy seven months prior to testing improved the ability of thyroid hormones to restore isoproterenol relaxation of the aorta. The loss of relaxation with age could be due in part to a pituitary mediated loss of responsiveness of aortic tissue to thyroid hormones. The data provide new evidence for the importance of thyroid hormones in beta-adrenergic receptor mediated vascular relaxation and demonstrate that the loss of aortic relaxation with aging can be reversed.", "contents": "Vascular relaxation, aging and thyroid hormones. Previous work indicates vascular can be studied in vitro and that there is a marked age-associated decrease in the ability of rat aortic strips to relax in response to beta-adrenergic agonists. The present studies were aimed at better understanding the role of thyroid hormones in vascular relaxation and aging. Removal of the thyroid gland from young rats resulted in a decrease in the ability of isoproterenol to relax the aorta. Relaxation caused by nitroglycerin, a non-specific relaxant, was not impaired by thyroidectomy. In 22-month-old rats, isoproterenol caused no relaxation unless exogenous thyroid hormones were administered. Hypophysectomy seven months prior to testing improved the ability of thyroid hormones to restore isoproterenol relaxation of the aorta. The loss of relaxation with age could be due in part to a pituitary mediated loss of responsiveness of aortic tissue to thyroid hormones. The data provide new evidence for the importance of thyroid hormones in beta-adrenergic receptor mediated vascular relaxation and demonstrate that the loss of aortic relaxation with aging can be reversed."}
{"id": "PMID:216859", "title": "[Skin manifestations in renal transplants].", "content": "The authors studied the skin disorders in 50 patients who have undergone renal transplantation. They observed: -- Viral infections (herpes simplex, herpes Zoster, warts) in 56% of the patients. -- Bacterial infections in 36%, resulting in septicemia in 8% of the cases. -- Fungal infections in 26% of the patients. These infections appeared more severe than usual and recurred frequently. The occurence of several infections processes in the same patient was not uncommon. The clinical aspect and high incidence of various infections is related to immunosuppresive therapy. However, there is no clear-cut correlation between the type of infection and the type of treatment used. -- Squamous cell carcinoma occured in one patient. A high incidence of malignancies is known to occur in immunosuppressed patients. -- Skin signs related to hemodialysis (pruritus, hypermelanosis, skin dryness, vascular disturbances) regressed. -- The incidence of adverse reactions to drugs was high. -- 4 cases of ulcerations of the oral mucosa probably related to Azathioprine were observed.", "contents": "[Skin manifestations in renal transplants]. The authors studied the skin disorders in 50 patients who have undergone renal transplantation. They observed: -- Viral infections (herpes simplex, herpes Zoster, warts) in 56% of the patients. -- Bacterial infections in 36%, resulting in septicemia in 8% of the cases. -- Fungal infections in 26% of the patients. These infections appeared more severe than usual and recurred frequently. The occurence of several infections processes in the same patient was not uncommon. The clinical aspect and high incidence of various infections is related to immunosuppresive therapy. However, there is no clear-cut correlation between the type of infection and the type of treatment used. -- Squamous cell carcinoma occured in one patient. A high incidence of malignancies is known to occur in immunosuppressed patients. -- Skin signs related to hemodialysis (pruritus, hypermelanosis, skin dryness, vascular disturbances) regressed. -- The incidence of adverse reactions to drugs was high. -- 4 cases of ulcerations of the oral mucosa probably related to Azathioprine were observed."}
{"id": "PMID:216863", "title": "[Aspects to the malignoma of the parotid gland and extratemporal facial nerve surgery (author's transl)].", "content": "Malignomas of the great salivary glands are--after own examinations--localized to ca. 90% in the parotid gland and ca. 10% in the sublingual gland. The frequency of different malignomas of the parotid gland, their age and sex incidence, pareses of the facial nerve before therapy, methods of therapy, relapses, letality and survival time are discussed. On own cases the method of extra-temporal reconstructive plastic surgery of the facial nerve is demonstrated.", "contents": "[Aspects to the malignoma of the parotid gland and extratemporal facial nerve surgery (author's transl)]. Malignomas of the great salivary glands are--after own examinations--localized to ca. 90% in the parotid gland and ca. 10% in the sublingual gland. The frequency of different malignomas of the parotid gland, their age and sex incidence, pareses of the facial nerve before therapy, methods of therapy, relapses, letality and survival time are discussed. On own cases the method of extra-temporal reconstructive plastic surgery of the facial nerve is demonstrated."}
{"id": "PMID:216865", "title": "[Islet cell carcinoma causing Verner-Morrison syndrome (author's transl)].", "content": "Predominant symptoms of the Verner-Morrison syndrome are diarrhea and hypokalemia; further symptoms can be impaired carbohydrate tolerance, hypercalcemia distension of the intestine and skin alterations. Diagnosis can be confirmed by computer tomography, angiography and demonstration of increased plasma levels of VIP and GIP. This syndrome is due to islet cell carcinoma of the pancreas in about one third of all cases observed. Total duodeno-pancreatectomy has to be performed, if surgery is possible at all. Patients who cannot be operated upon may receive combined cytostatic therapy.", "contents": "[Islet cell carcinoma causing Verner-Morrison syndrome (author's transl)]. Predominant symptoms of the Verner-Morrison syndrome are diarrhea and hypokalemia; further symptoms can be impaired carbohydrate tolerance, hypercalcemia distension of the intestine and skin alterations. Diagnosis can be confirmed by computer tomography, angiography and demonstration of increased plasma levels of VIP and GIP. This syndrome is due to islet cell carcinoma of the pancreas in about one third of all cases observed. Total duodeno-pancreatectomy has to be performed, if surgery is possible at all. Patients who cannot be operated upon may receive combined cytostatic therapy."}
{"id": "PMID:216878", "title": "Gastroenteritis: etiology, pathophysiology and clinical manifestations.", "content": "The infectious etiologic agents of gastroenteritis are manifold and have only recently been studied in greater depth. Part of the problem in studies pertaining to diarrhea is the difficulty in identifying fecal \"pathogens\" among an enormous number of indigenous fecal microorganisms. Finally, the recognition of the pathogenicity of enterotoxins has created an awareness of the complexity of gastrointestinal physiology with host-parasite interactions.", "contents": "Gastroenteritis: etiology, pathophysiology and clinical manifestations. The infectious etiologic agents of gastroenteritis are manifold and have only recently been studied in greater depth. Part of the problem in studies pertaining to diarrhea is the difficulty in identifying fecal \"pathogens\" among an enormous number of indigenous fecal microorganisms. Finally, the recognition of the pathogenicity of enterotoxins has created an awareness of the complexity of gastrointestinal physiology with host-parasite interactions."}
{"id": "PMID:216879", "title": "[Dynamics of changes in rat osseous system in chronic cadmium poisoning].", "content": "The rats were given subcutaneously CdSO4 in doses 0.7 mg/kg of body weight once a week during one year. After the lapse of 6, 9 and 12 months, the animals were sacrificed and their blood was used to determine the preselected biochemical indices (erythrocytes, hemoglobin, hematocrit, levels of protein, albumins, globulins GOT, GPT, AP and its isoenzymes, calcium, inorganic phosphorus, urea and creatinines). Simultaneously radiological examinations were performed on prepared and dehydrated long bones being estimated. Changes were revealed in morphological parameters of long bones with a marked demineralisation of epiphyses after 9 months of investigations. The above changes were found to correlate with those referring to biochemical indices levels, intensifying with the increase of the exposure period.", "contents": "[Dynamics of changes in rat osseous system in chronic cadmium poisoning]. The rats were given subcutaneously CdSO4 in doses 0.7 mg/kg of body weight once a week during one year. After the lapse of 6, 9 and 12 months, the animals were sacrificed and their blood was used to determine the preselected biochemical indices (erythrocytes, hemoglobin, hematocrit, levels of protein, albumins, globulins GOT, GPT, AP and its isoenzymes, calcium, inorganic phosphorus, urea and creatinines). Simultaneously radiological examinations were performed on prepared and dehydrated long bones being estimated. Changes were revealed in morphological parameters of long bones with a marked demineralisation of epiphyses after 9 months of investigations. The above changes were found to correlate with those referring to biochemical indices levels, intensifying with the increase of the exposure period."}
{"id": "PMID:216880", "title": "[Concentration of serum iron and transferrin saturation with iron as indices of changes resulting from chronic exposure to chemicals in industry].", "content": "An attempt was undertaken to use the following indices of systemic changes resulting from longlasting occupational exposure to some chemicals: -- ferrum concentration in blood serum, the level of latent capacity to bind ferrum, and the degree of transferrin saturation with ferrum. The examination involved 177 clinically healthy men, aged 18--60. The control group consisted of 40 healthy men, aged 22--60. In 30.5% of persons, deviations were found, which might be induced by disturbances in general immunity of the organism, whereas in 16,4% the deviations might indicate chronic systemic changes.", "contents": "[Concentration of serum iron and transferrin saturation with iron as indices of changes resulting from chronic exposure to chemicals in industry]. An attempt was undertaken to use the following indices of systemic changes resulting from longlasting occupational exposure to some chemicals: -- ferrum concentration in blood serum, the level of latent capacity to bind ferrum, and the degree of transferrin saturation with ferrum. The examination involved 177 clinically healthy men, aged 18--60. The control group consisted of 40 healthy men, aged 22--60. In 30.5% of persons, deviations were found, which might be induced by disturbances in general immunity of the organism, whereas in 16,4% the deviations might indicate chronic systemic changes."}
{"id": "PMID:216881", "title": "Normocholesterolemic dysbetalipoproteinemia with xanthomatosis.", "content": "A patient is described who has marked palmar xanthomatosis associated with a normal concentration of plasma cholesterol. Analysis of xanthomas revealed them to contain large quantities of cholesterol with both intra- and extracellular lipids. Examination of plasma lipoproteins showed them to be consistent with a pattern of dysbetalipoproteinemia (Type III hyperlipoproteinemia). VLDL had beta-mobility on electrophoresis, a high cholesterol/triglyceride ratio, and increased apoprotein B. However, arginine-rich apoprotein was not increased in VLDL, in contrast to hypercholesterolemic patients with the Type III pattern. Nevertheless, the E3 subfraction of the arginine-rich apoprotein was virtually absent, which is characteristic of dysbetalipoproteinemia. Cholesterol and bile acid synthesis were in the normal range. Thus, of particular interest was the development of severe xanthomatosis without hypercholesterolemia in this patient. Therefore, tissue accumulation of cholesterol was apparently the result of a qualitative abnormality in lipoproteins and not due to an excess of plasma cholesterol.", "contents": "Normocholesterolemic dysbetalipoproteinemia with xanthomatosis. A patient is described who has marked palmar xanthomatosis associated with a normal concentration of plasma cholesterol. Analysis of xanthomas revealed them to contain large quantities of cholesterol with both intra- and extracellular lipids. Examination of plasma lipoproteins showed them to be consistent with a pattern of dysbetalipoproteinemia (Type III hyperlipoproteinemia). VLDL had beta-mobility on electrophoresis, a high cholesterol/triglyceride ratio, and increased apoprotein B. However, arginine-rich apoprotein was not increased in VLDL, in contrast to hypercholesterolemic patients with the Type III pattern. Nevertheless, the E3 subfraction of the arginine-rich apoprotein was virtually absent, which is characteristic of dysbetalipoproteinemia. Cholesterol and bile acid synthesis were in the normal range. Thus, of particular interest was the development of severe xanthomatosis without hypercholesterolemia in this patient. Therefore, tissue accumulation of cholesterol was apparently the result of a qualitative abnormality in lipoproteins and not due to an excess of plasma cholesterol."}
{"id": "PMID:216883", "title": "Relationship between lipolysis, cyclic AMP, and fat-cell size in human adipose tissue during fasting and in diabetes mellitus.", "content": "The in vitro relationship between fat-cell size, glycerol release, and peak concentration of cyclic AMP was investigated in human adipose tissue obtained from 25 obese nondiabetic patients before and after a 7-day fast and from 23 patients with untreated diabetes mellitus. In the obese nondiabetic patients there was a linear correlation between fat-cell size and cyclic AMP concentration, and fat-cell size and the rate of lipolysis. This was found both in nonfasting and fasting nondiabetic patients. However, in diabetes mellitus, there was only a relationship between cell size and cyclic AMP concentration. The alpha-adrenergic and beta-adrenergic activity in human adipose tissue was assessed by comparing the effect of isoprenaline and noradrenaline on the cyclic AMP concentration. The activity of both receptors was found to be increased in fasting obese patients and in diabetics. In both conditions the alpha-adrenergic response to catecholamines predominated in small fat cells, whereas in large ones the beta response predominated. The results suggest that during fasting and in diabetes mellitus there is a correlation between fat-cell size and the responsiveness of the adrenergic receptors. Thus, catecholamines may be involved in regulating the fat-cell volume. The view is expressed that the abnormal catecholamine-induced lipolysis is solely due to changes at the level of the adrenergic receptors during fasting, whereas in diabetes mellitus the sequentional activation of lipolysis is disturbed at deeper sites as well.", "contents": "Relationship between lipolysis, cyclic AMP, and fat-cell size in human adipose tissue during fasting and in diabetes mellitus. The in vitro relationship between fat-cell size, glycerol release, and peak concentration of cyclic AMP was investigated in human adipose tissue obtained from 25 obese nondiabetic patients before and after a 7-day fast and from 23 patients with untreated diabetes mellitus. In the obese nondiabetic patients there was a linear correlation between fat-cell size and cyclic AMP concentration, and fat-cell size and the rate of lipolysis. This was found both in nonfasting and fasting nondiabetic patients. However, in diabetes mellitus, there was only a relationship between cell size and cyclic AMP concentration. The alpha-adrenergic and beta-adrenergic activity in human adipose tissue was assessed by comparing the effect of isoprenaline and noradrenaline on the cyclic AMP concentration. The activity of both receptors was found to be increased in fasting obese patients and in diabetics. In both conditions the alpha-adrenergic response to catecholamines predominated in small fat cells, whereas in large ones the beta response predominated. The results suggest that during fasting and in diabetes mellitus there is a correlation between fat-cell size and the responsiveness of the adrenergic receptors. Thus, catecholamines may be involved in regulating the fat-cell volume. The view is expressed that the abnormal catecholamine-induced lipolysis is solely due to changes at the level of the adrenergic receptors during fasting, whereas in diabetes mellitus the sequentional activation of lipolysis is disturbed at deeper sites as well."}
{"id": "PMID:216887", "title": "Insulin release in response to calcium in the diagnosis of insulinoma.", "content": "A calcium infusion (4 mg Ca++/kg/hr) significantly increased plasma insulin levels and reduced blood glucose in 4 patients with insulin-secreting pancreatic islet cell tumors. These parameters were not altered by a similar infusion of calcium in normal volunteers, 2 patients with alimentary hypoglycemia, and 2 with functional hypoglycemia. No difference in response was observed between patients with benign and malignant beta-cell tumors. Infusion of diazoxide (600 mg) with calcium blocked the stimulation of the latter on insulin secretion. The results indicate the usefulness of calcium infusion in the diagnosis of insulin-secreting tumor.", "contents": "Insulin release in response to calcium in the diagnosis of insulinoma. A calcium infusion (4 mg Ca++/kg/hr) significantly increased plasma insulin levels and reduced blood glucose in 4 patients with insulin-secreting pancreatic islet cell tumors. These parameters were not altered by a similar infusion of calcium in normal volunteers, 2 patients with alimentary hypoglycemia, and 2 with functional hypoglycemia. No difference in response was observed between patients with benign and malignant beta-cell tumors. Infusion of diazoxide (600 mg) with calcium blocked the stimulation of the latter on insulin secretion. The results indicate the usefulness of calcium infusion in the diagnosis of insulin-secreting tumor."}
{"id": "PMID:216888", "title": "The syndromes of primary hormone resistance.", "content": "The clinical features, genetics, pathophysiology, and management of endocrine diseases in which primary hormone resistance is the fundamental defect have been reviewed. Primary hormone resistance has been documented for nearly all hormones--vasopressin, parathyroid hormone, growth hormone, adrenocroticotropin, thyrotropin, gonadotropins, insulin, androgens, cortisol, aldosterone, progesterone, thyroid hormones, and vitamin D. A striking exception is estradiol, a steroid that may be vital for early embryonic development. Most of the hormone unresponsiveness syndromes represent only partial defects, and it is likely that most such patients go unrecognized. Therefore, hormone resistance should be suspected not only when a patient presents with hypofunction of particular endocrine system combined with high endogenous hormone levels but also whenever apparently normal function of an endocrine system is associated with inappropriately elevated levels of the corresponding hormone. The value of these defects in hormone responsiveness as a natural laboratory for the study of the normal mechanisms of hormone action is discussed.", "contents": "The syndromes of primary hormone resistance. The clinical features, genetics, pathophysiology, and management of endocrine diseases in which primary hormone resistance is the fundamental defect have been reviewed. Primary hormone resistance has been documented for nearly all hormones--vasopressin, parathyroid hormone, growth hormone, adrenocroticotropin, thyrotropin, gonadotropins, insulin, androgens, cortisol, aldosterone, progesterone, thyroid hormones, and vitamin D. A striking exception is estradiol, a steroid that may be vital for early embryonic development. Most of the hormone unresponsiveness syndromes represent only partial defects, and it is likely that most such patients go unrecognized. Therefore, hormone resistance should be suspected not only when a patient presents with hypofunction of particular endocrine system combined with high endogenous hormone levels but also whenever apparently normal function of an endocrine system is associated with inappropriately elevated levels of the corresponding hormone. The value of these defects in hormone responsiveness as a natural laboratory for the study of the normal mechanisms of hormone action is discussed."}
{"id": "PMID:216890", "title": "Metabolic basis of endotoxicosis.", "content": "Whereas as specific immunological responses are elicited only after a delay of some days, alteration in various biochemical parameters is observed within 1-2 h of endotoxin administration in a number of animal species. Generally the level of several hepatic enzymes (tryptophan pyrrolase, phophoenol pyruvate carboxykinase) metabolites (glycogen, NAD) and intermediates in the energetic homeostasis is lowered by the toxin, increased by the glucocorticoid hormones and maintained at the normal level when the toxic effects of endotoxin are annulled by the counter effects of the protective agent (such as cortisone). Antagonism is also noted on the synthesis of cellular RNA, DNA and protein. However, no unitary process has as yet been singled out to possessing a cause and effect relationship between toxicity and survival. In the intact animal, it is not possible to affirm whether the toxin exerts a direct effect on the organ, the cell or the process in question, especially since endotoxin is phagocytized by the cells of the reticuloendothelial system (RES) in the liver and elsewhere and since the biochemical parameters are a property of the organ specific epithelial cells. Experiments with tissue slices suffer from the problem of permeability and uptake in vitro and are not readily reproducible. Isolated cells in culture are theoretically ideal but exhibit loss of functions and undergo neoplastic type of transformation that renders them unsuitable for relevant biochemical studies. Primary explants of the hepatocytes and the RE cells, as well as hybrids between these two cellular types appear more promising. However, at the moment, isolated liver preparations perfused in vitro offer the best solution by exhibiting intact function, morphology and excellent reproducibility. Collectively, it is tempting to speculate that the extent of subsequent immunological response is a reflection of the preceding biochemical processing, that both sorts of events are in some way mediated by the RE cells, and that the latter may most easily be studied in the intact liver in vitro.", "contents": "Metabolic basis of endotoxicosis. Whereas as specific immunological responses are elicited only after a delay of some days, alteration in various biochemical parameters is observed within 1-2 h of endotoxin administration in a number of animal species. Generally the level of several hepatic enzymes (tryptophan pyrrolase, phophoenol pyruvate carboxykinase) metabolites (glycogen, NAD) and intermediates in the energetic homeostasis is lowered by the toxin, increased by the glucocorticoid hormones and maintained at the normal level when the toxic effects of endotoxin are annulled by the counter effects of the protective agent (such as cortisone). Antagonism is also noted on the synthesis of cellular RNA, DNA and protein. However, no unitary process has as yet been singled out to possessing a cause and effect relationship between toxicity and survival. In the intact animal, it is not possible to affirm whether the toxin exerts a direct effect on the organ, the cell or the process in question, especially since endotoxin is phagocytized by the cells of the reticuloendothelial system (RES) in the liver and elsewhere and since the biochemical parameters are a property of the organ specific epithelial cells. Experiments with tissue slices suffer from the problem of permeability and uptake in vitro and are not readily reproducible. Isolated cells in culture are theoretically ideal but exhibit loss of functions and undergo neoplastic type of transformation that renders them unsuitable for relevant biochemical studies. Primary explants of the hepatocytes and the RE cells, as well as hybrids between these two cellular types appear more promising. However, at the moment, isolated liver preparations perfused in vitro offer the best solution by exhibiting intact function, morphology and excellent reproducibility. Collectively, it is tempting to speculate that the extent of subsequent immunological response is a reflection of the preceding biochemical processing, that both sorts of events are in some way mediated by the RE cells, and that the latter may most easily be studied in the intact liver in vitro."}
{"id": "PMID:216891", "title": "Concanavalin A-mediated agglutination of 3T3 cells after exposure to UV-irradiated herpes simplex virus.", "content": "Studies were made to determine the effect of UV-irradiation of herpes simplex virus (HSV) on Concanavalin A (Con-A)-mediated agglutination of 3T3 cells. There were three different phases of agglutination by Con-A of cells infected with HSV. The agglutinability began to increase from 3 or 4 hr, or 72 hr after exposure of cells to HSV. The early-appearing agglutinability was further divided into two phases, based on its sensitivity to metabolic inhibitors. These were tentatively called \"Early 1 or inhibitor sensitive\", \"Early 2 or inhibitor insensitive\" and \"Late\" agglutinability. \"Early 1\" agglutination, detected from 3 hr post infection (pi), was induced by treating cells with HSV, either active or UV-irradiated for less than 5 min and was inhibited when actinomycin D (1 microgram/ml) or cycloheximide (50 microgram/ml) was added to the cultures. \"Early 2\" agglutination began to increase from 4 hr pi when cells were inoculated with HSV irradiated for 7 to 20 min and was not affected by either inhibitor. HSV irradiated for 6 min failed to induce either agglutinability. \"Late\" agglutination, observed 72 hr pi, was detected in cultures which had been treated with HSV irradiated for 4 to 15 min. Among those, virus irradiated for 6 to 8 min was most efficient. HSV-transformed cells were also agglutinated without exception by low concentrations of Con-A.", "contents": "Concanavalin A-mediated agglutination of 3T3 cells after exposure to UV-irradiated herpes simplex virus. Studies were made to determine the effect of UV-irradiation of herpes simplex virus (HSV) on Concanavalin A (Con-A)-mediated agglutination of 3T3 cells. There were three different phases of agglutination by Con-A of cells infected with HSV. The agglutinability began to increase from 3 or 4 hr, or 72 hr after exposure of cells to HSV. The early-appearing agglutinability was further divided into two phases, based on its sensitivity to metabolic inhibitors. These were tentatively called \"Early 1 or inhibitor sensitive\", \"Early 2 or inhibitor insensitive\" and \"Late\" agglutinability. \"Early 1\" agglutination, detected from 3 hr post infection (pi), was induced by treating cells with HSV, either active or UV-irradiated for less than 5 min and was inhibited when actinomycin D (1 microgram/ml) or cycloheximide (50 microgram/ml) was added to the cultures. \"Early 2\" agglutination began to increase from 4 hr pi when cells were inoculated with HSV irradiated for 7 to 20 min and was not affected by either inhibitor. HSV irradiated for 6 min failed to induce either agglutinability. \"Late\" agglutination, observed 72 hr pi, was detected in cultures which had been treated with HSV irradiated for 4 to 15 min. Among those, virus irradiated for 6 to 8 min was most efficient. HSV-transformed cells were also agglutinated without exception by low concentrations of Con-A."}
{"id": "PMID:216895", "title": "[Influence of \"prudent\" diet and clofibrate upon apolipoprotein B in hyperlipoproteinemia type IIa (author's transl)].", "content": "If patients with hyperlipoproteinemia type IIa are treated with diet and additionally over a period of two weeks with 2 grams of Clofibrate daily, the cholesterol-level in the serum decreases. This decrease is caused mainly by a reduction of the apolipoprotein B and the LDL-cholesterol in serum. If elevated cholesterol-levels in the serum are reduced through a \"prudent\" diet, the concentration of apolipoprotein B in serum remains the same. It is not fully understood which influence a diet, which is rich in poly-unsaturated fatty acids and has a low content of saturated fatty acids and carbohydrates, has upon the lipoproteins in the serum. The mode of action of this diet and its significance for the concentration of HDL need further investigation.", "contents": "[Influence of \"prudent\" diet and clofibrate upon apolipoprotein B in hyperlipoproteinemia type IIa (author's transl)]. If patients with hyperlipoproteinemia type IIa are treated with diet and additionally over a period of two weeks with 2 grams of Clofibrate daily, the cholesterol-level in the serum decreases. This decrease is caused mainly by a reduction of the apolipoprotein B and the LDL-cholesterol in serum. If elevated cholesterol-levels in the serum are reduced through a \"prudent\" diet, the concentration of apolipoprotein B in serum remains the same. It is not fully understood which influence a diet, which is rich in poly-unsaturated fatty acids and has a low content of saturated fatty acids and carbohydrates, has upon the lipoproteins in the serum. The mode of action of this diet and its significance for the concentration of HDL need further investigation."}
{"id": "PMID:216898", "title": "Evaluation of a bovine virus diarrhea vaccine.", "content": "Singer Strain bovine virus diarrhea (BVD) modified live-virus vaccine, produced in a continuous bovine cell line using equine serum in the growth medium, evoked a high level of serum antibodies and protected against virulent challenge in vaccinated calves. Transmission of vaccinal virus from vaccinated cattle to susceptible controls did not occur when vaccinated and nonvaccinated cattle were kept in constant contact for 23 days. Postvaccinal reactions to the viral vaccine were not observed in vaccinated cattle from 10 feedlots or in cattle vaccinated with multiple doses of the experimental vaccine.", "contents": "Evaluation of a bovine virus diarrhea vaccine. Singer Strain bovine virus diarrhea (BVD) modified live-virus vaccine, produced in a continuous bovine cell line using equine serum in the growth medium, evoked a high level of serum antibodies and protected against virulent challenge in vaccinated calves. Transmission of vaccinal virus from vaccinated cattle to susceptible controls did not occur when vaccinated and nonvaccinated cattle were kept in constant contact for 23 days. Postvaccinal reactions to the viral vaccine were not observed in vaccinated cattle from 10 feedlots or in cattle vaccinated with multiple doses of the experimental vaccine."}
{"id": "PMID:216899", "title": "A regulatory system controlling the production of cytochrome aa3 in Neurospora crassa.", "content": "The mitochondria of the cyt-2-1, cya-3-16, cya-4-23 and 299-1 nuclear mutants and the [mi-3] and [exn-5] cytoplasmic mutants of Neurospora crassa are deficient in cytochrome aa3, while the cyb-1-1 and cyb-2-1 mutants have mitochondrial b-cytochrome deficiencies. However, the mitochondria from cyb-1-1 cyt-2-1, cyb-1-1 [mi-3] and cyb-2-1 [mi-3] double mutants contain 30% to 50% of the amount of cytochrome aa3 that is present in mitochondria from wild-type; i.e. cyb-1-1 and cyb-2-2 act as suppressors of the cytochrome aa3 deficiency phenotypes that are associated with cyt-2-1 and [mi-3] mutations. The production of cytochrome aa3 can be induced in cyt-2-1 and [mi-3] by growing cells in medium containing antimycin A, an inhibitor of electron transport in the cytochrome bc1 segment of the mitochondrial electrontransport chain. Moreover, the growth of the [mi-3] mutant is strongly stimulated by low concentrations of antimycin A. The induction of cytochrome aa3 by antimycin treatments does not occur in [exn-5], cya-4-23 and 299-1 cells; but does take place in cya-3-16 cells. Although some of the seven constituent polypeptides of cytochrome aa3 are present in mitochondria of [mi-3], the holoenzyme complex is not formed in the mutant. In contrast, the mitochondria of cyb-1-1 [mi-3] and cyb-2-2 [mi-3] double mutants contain a fully assembled cytochrome oxidase complex as well as some unassembled subunit polypeptides. The observations are indicative of the existence of at least two regulatory systems controlling the production of cytochrome aa3. One of the circuits appears to control the basal or \"constitutive\" production of cytochrome oxidase, the other seems to coordinate the level of cytochrome aa3 with some function of the mitochondrial cytochrome bc1 complex, possibly electron transport.", "contents": "A regulatory system controlling the production of cytochrome aa3 in Neurospora crassa. The mitochondria of the cyt-2-1, cya-3-16, cya-4-23 and 299-1 nuclear mutants and the [mi-3] and [exn-5] cytoplasmic mutants of Neurospora crassa are deficient in cytochrome aa3, while the cyb-1-1 and cyb-2-1 mutants have mitochondrial b-cytochrome deficiencies. However, the mitochondria from cyb-1-1 cyt-2-1, cyb-1-1 [mi-3] and cyb-2-1 [mi-3] double mutants contain 30% to 50% of the amount of cytochrome aa3 that is present in mitochondria from wild-type; i.e. cyb-1-1 and cyb-2-2 act as suppressors of the cytochrome aa3 deficiency phenotypes that are associated with cyt-2-1 and [mi-3] mutations. The production of cytochrome aa3 can be induced in cyt-2-1 and [mi-3] by growing cells in medium containing antimycin A, an inhibitor of electron transport in the cytochrome bc1 segment of the mitochondrial electrontransport chain. Moreover, the growth of the [mi-3] mutant is strongly stimulated by low concentrations of antimycin A. The induction of cytochrome aa3 by antimycin treatments does not occur in [exn-5], cya-4-23 and 299-1 cells; but does take place in cya-3-16 cells. Although some of the seven constituent polypeptides of cytochrome aa3 are present in mitochondria of [mi-3], the holoenzyme complex is not formed in the mutant. In contrast, the mitochondria of cyb-1-1 [mi-3] and cyb-2-2 [mi-3] double mutants contain a fully assembled cytochrome oxidase complex as well as some unassembled subunit polypeptides. The observations are indicative of the existence of at least two regulatory systems controlling the production of cytochrome aa3. One of the circuits appears to control the basal or \"constitutive\" production of cytochrome oxidase, the other seems to coordinate the level of cytochrome aa3 with some function of the mitochondrial cytochrome bc1 complex, possibly electron transport."}
{"id": "PMID:216901", "title": "Eukaryotic ribosomal proteins stimulate Escherichia coli stringent factor to synthesize guanosine 5'-diphosphate, 3'-diphosphate (ppGpp) and guanosine 5'-triphosphate, 3'-diphosphate (ppGpp).", "content": "When supplemented with Escherichia coli stringent factor, 80S ribosomes from various sources failed to support guanosine tetra- and pentaphosphate ((p)ppGpp) synthesis. In contrast, ribosomal proteins from 80S, 60S or 40S particles (mouse embryos, rabbit reticulocytes) crossreacted with the E. coli stringent factor. Significant stimulation of (p)ppGpp synthesis was achieved with a concentration as low as 5 micrograms of ribosomal proteins/ml. These observations may provide additional crtieria to detect homologies between eukaryotic and prokaryotic ribosomal proteins.", "contents": "Eukaryotic ribosomal proteins stimulate Escherichia coli stringent factor to synthesize guanosine 5'-diphosphate, 3'-diphosphate (ppGpp) and guanosine 5'-triphosphate, 3'-diphosphate (ppGpp). When supplemented with Escherichia coli stringent factor, 80S ribosomes from various sources failed to support guanosine tetra- and pentaphosphate ((p)ppGpp) synthesis. In contrast, ribosomal proteins from 80S, 60S or 40S particles (mouse embryos, rabbit reticulocytes) crossreacted with the E. coli stringent factor. Significant stimulation of (p)ppGpp synthesis was achieved with a concentration as low as 5 micrograms of ribosomal proteins/ml. These observations may provide additional crtieria to detect homologies between eukaryotic and prokaryotic ribosomal proteins."}
{"id": "PMID:216900", "title": "Nuclear mutants of Neurospora crassa temperature-sensitive for the synthesis of cytochrome aa3. I. Isolation and preliminary characterization.", "content": "Three nuclear mutants of Neurospora crassa, temperature-sensitive for the synthesis of cytochrome aa3 have been isolated. When grown at 41 degrees C the mutants have large amounts of KCN-insensitive respiration, reduced amounts of cytochrome aa3 and cytochrome c oxidase activity, and grow more slowly than wild-type cultures grown at the same temperature. When the mutants are grown at 23 degrees C, they are virtually indistinguishable from wild-type strains. The mutants were selected on the basis of their slow growth at 41 degrees C in medium containing salicylhydroxamic acid, and by their inability to reduce 2,3,5-triphenyltetrazolium chloride at 41 degrees c. The selecttion technique was designed to eliminate mutants that did not carry thermolabile electron transport chain components. However, studies on the thermolability of the cytochrome oxidase activity in isolated mitochondria indicate that the enzyme of the mutants is no more susceptible to heat denaturation than is the enzyme in wild-type mitochondria. This suggests that the synthesis or assembly of cytochrome aa3 may be altered in the mutants at the restrictive temperature.", "contents": "Nuclear mutants of Neurospora crassa temperature-sensitive for the synthesis of cytochrome aa3. I. Isolation and preliminary characterization. Three nuclear mutants of Neurospora crassa, temperature-sensitive for the synthesis of cytochrome aa3 have been isolated. When grown at 41 degrees C the mutants have large amounts of KCN-insensitive respiration, reduced amounts of cytochrome aa3 and cytochrome c oxidase activity, and grow more slowly than wild-type cultures grown at the same temperature. When the mutants are grown at 23 degrees C, they are virtually indistinguishable from wild-type strains. The mutants were selected on the basis of their slow growth at 41 degrees C in medium containing salicylhydroxamic acid, and by their inability to reduce 2,3,5-triphenyltetrazolium chloride at 41 degrees c. The selecttion technique was designed to eliminate mutants that did not carry thermolabile electron transport chain components. However, studies on the thermolability of the cytochrome oxidase activity in isolated mitochondria indicate that the enzyme of the mutants is no more susceptible to heat denaturation than is the enzyme in wild-type mitochondria. This suggests that the synthesis or assembly of cytochrome aa3 may be altered in the mutants at the restrictive temperature."}
{"id": "PMID:216902", "title": "Petite deletion map of the mitochondrial oxi3 region in Saccharomyces cerevisiae.", "content": "Fifty eight mitochondrial mutants (p + mit- mutants), all deficient in cytochrome oxidase activity and previously assigned to the genetic region oxi3 on the mitochondrial DNA, were mapped by the method of \"petite deletion mapping\". This procedure resulted in the identification of at least twenty one different classes of oxi3 mutants, which could be arranged in a linear order. Moreover, it provided a set of twenty three p- petite mutants, each containing a differentially deleted mit DNA segment included in the oxi3 region. The two sets of mutants, p+ oxi3- and p- oxi3+, will be of interest for a further genetic and physical analysis of this mitochondrial DNA segment which spans over about ten thousand base pairs and controls the subunit I of cytochrome oxidase.", "contents": "Petite deletion map of the mitochondrial oxi3 region in Saccharomyces cerevisiae. Fifty eight mitochondrial mutants (p + mit- mutants), all deficient in cytochrome oxidase activity and previously assigned to the genetic region oxi3 on the mitochondrial DNA, were mapped by the method of \"petite deletion mapping\". This procedure resulted in the identification of at least twenty one different classes of oxi3 mutants, which could be arranged in a linear order. Moreover, it provided a set of twenty three p- petite mutants, each containing a differentially deleted mit DNA segment included in the oxi3 region. The two sets of mutants, p+ oxi3- and p- oxi3+, will be of interest for a further genetic and physical analysis of this mitochondrial DNA segment which spans over about ten thousand base pairs and controls the subunit I of cytochrome oxidase."}
{"id": "PMID:216903", "title": "Dephosphorylation of histone H1 after mengovirus infection of Ehrlich ascites tumor cells.", "content": "The effect of mengovirus infection on the extent of phosphorylation of histone H1 was studied in Ehrlich ascites tumor cells. After prelabeling of the nuclear protein with [32P] orthophosphate, the excorporation of radioactivity was followed as a function of time postinfection. Employing high-resolution polyacrylamide gradient slab gel electrophoresis and autoradiography, it was found that, compared to a relatively slow turnover of phosphate groups in histone H1 in mock-infected cells, in mengovirus-infected cells the excorporation of radiolabel from histone H1 was significantly enhanced. In the latter case, the decrease of histone-bound radioactivity was paralleled by a reduction of the band multiplicity in the histone H1 region of the electrophoresis profile. It was also shown that the microheterogeneity in the histone H1 complements isolated at various times postinfection was reduced to the same basal 3-band level by incubation of the nuclear protein fractions in the presence of alkaline phosphatase. After this treatment, the band multiplicity equaled that found in histone H1 from stationary cells.", "contents": "Dephosphorylation of histone H1 after mengovirus infection of Ehrlich ascites tumor cells. The effect of mengovirus infection on the extent of phosphorylation of histone H1 was studied in Ehrlich ascites tumor cells. After prelabeling of the nuclear protein with [32P] orthophosphate, the excorporation of radioactivity was followed as a function of time postinfection. Employing high-resolution polyacrylamide gradient slab gel electrophoresis and autoradiography, it was found that, compared to a relatively slow turnover of phosphate groups in histone H1 in mock-infected cells, in mengovirus-infected cells the excorporation of radiolabel from histone H1 was significantly enhanced. In the latter case, the decrease of histone-bound radioactivity was paralleled by a reduction of the band multiplicity in the histone H1 region of the electrophoresis profile. It was also shown that the microheterogeneity in the histone H1 complements isolated at various times postinfection was reduced to the same basal 3-band level by incubation of the nuclear protein fractions in the presence of alkaline phosphatase. After this treatment, the band multiplicity equaled that found in histone H1 from stationary cells."}
{"id": "PMID:216904", "title": "30S ribosomal proteins cross-linked to 16S RNA by periodate oxidation followed by borohydride reduction.", "content": "Gel electrophoretic techniques have been used to reexamine the RNA-protein cross-linking reaction induced by periodate oxidation and borohydride reduction of 30S ribosomal subunits. The results show that a number of 30S ribosomal proteins become attached to intact 16S RNA by this method, in addition to those already published. It follows that this cross-linking technique as it stands is of little value as a topographical probe of the environment of the 3'-terminus of the 16S RNA.", "contents": "30S ribosomal proteins cross-linked to 16S RNA by periodate oxidation followed by borohydride reduction. Gel electrophoretic techniques have been used to reexamine the RNA-protein cross-linking reaction induced by periodate oxidation and borohydride reduction of 30S ribosomal subunits. The results show that a number of 30S ribosomal proteins become attached to intact 16S RNA by this method, in addition to those already published. It follows that this cross-linking technique as it stands is of little value as a topographical probe of the environment of the 3'-terminus of the 16S RNA."}
{"id": "PMID:216906", "title": "[Indication for and evaluation of plasmaprotein determinations (author's transl)].", "content": "All components of the \"fluid tissue\" blood should be considered as functional units. This seems familiar to physicians for the blood cells. For the dissolved plasmaproteins most doctors are, however, not yet used to think in functional terms. We propose a functional classification of well-characterized plasmaproteins, and a list of correlations between clinical conditions and protein changes. The clinician and the director of the laboratory have special knowledge and accordingly different tasks. An outline of the possible distribution of their duties and for their collaboration is given. We propose the stepwise evaluation of laboratory tests requested which in its details is obviously quite subjective and debatable. Accordingly, tests are categorized for routine, for special questions, and for scientific investigation. Finally, the clinician ought to know possible sources of error and mistake. For detailed advice, he may ask the director of the laboratory. If these principles--details may be modified--are respected, doctors should be able to obtain the laboratory data they need for diagnosis and treatment with minimal inconvenience to the patient and lowest cost to the community.", "contents": "[Indication for and evaluation of plasmaprotein determinations (author's transl)]. All components of the \"fluid tissue\" blood should be considered as functional units. This seems familiar to physicians for the blood cells. For the dissolved plasmaproteins most doctors are, however, not yet used to think in functional terms. We propose a functional classification of well-characterized plasmaproteins, and a list of correlations between clinical conditions and protein changes. The clinician and the director of the laboratory have special knowledge and accordingly different tasks. An outline of the possible distribution of their duties and for their collaboration is given. We propose the stepwise evaluation of laboratory tests requested which in its details is obviously quite subjective and debatable. Accordingly, tests are categorized for routine, for special questions, and for scientific investigation. Finally, the clinician ought to know possible sources of error and mistake. For detailed advice, he may ask the director of the laboratory. If these principles--details may be modified--are respected, doctors should be able to obtain the laboratory data they need for diagnosis and treatment with minimal inconvenience to the patient and lowest cost to the community."}
{"id": "PMID:216905", "title": "[Chemical modification of ferricytochrome c by N-(2,2',5,5'-tetramethyl-3-carboxypyrroline-1-oxyl)-imidazole].", "content": "Chemical modification of pig heart ferricytochrome C by the paramagentic analog of N-acetylimidazole-N-(2,2',5,5'-tetramethyl-3-carboxypyrroline-1-oxyl)-imidazole has been studied. Two main modified preparations, both with the single spin label per molecule, have been isolated by means of chromatography on CM-Sephadex C-25. The study of UV-difference spectra of the SL-preparations versus native Cyt C, the spectrophotometric titration of the tyrosine residues in modified proteins and the study of their reaction with hydroxylamine allow to conclude that one of these preparations (fraction II) is lysine modified Cyt C-SL(Lys)-Cyt C and the other (fraction III) is tyrosine modified protein-SL(Tyr)-Cyt C. From the present results and the data available in literature the most probable location of the modification sites in the three-dimentional structure of Cyt C is Tyr-74 in SL (Tyr)-Cyt C and one of the neighbouring lysil residues Lys 72 or Lys 73 in SL (Lys)-Cyt C on the molecular surface. From the absorbtion and CD-spectra of the modified and native Cyt C in the spectral interval 190--450 nm and from the high resolution PMR data the conclusion has been made that  the chemical modification does not alter the immediate vicinity of the heme group and the molecular structure of Cyt C as a whole. Therefore both SL-modified preparations might be useful for the conformational and functional investigations of Cyt C.", "contents": "[Chemical modification of ferricytochrome c by N-(2,2',5,5'-tetramethyl-3-carboxypyrroline-1-oxyl)-imidazole]. Chemical modification of pig heart ferricytochrome C by the paramagentic analog of N-acetylimidazole-N-(2,2',5,5'-tetramethyl-3-carboxypyrroline-1-oxyl)-imidazole has been studied. Two main modified preparations, both with the single spin label per molecule, have been isolated by means of chromatography on CM-Sephadex C-25. The study of UV-difference spectra of the SL-preparations versus native Cyt C, the spectrophotometric titration of the tyrosine residues in modified proteins and the study of their reaction with hydroxylamine allow to conclude that one of these preparations (fraction II) is lysine modified Cyt C-SL(Lys)-Cyt C and the other (fraction III) is tyrosine modified protein-SL(Tyr)-Cyt C. From the present results and the data available in literature the most probable location of the modification sites in the three-dimentional structure of Cyt C is Tyr-74 in SL (Tyr)-Cyt C and one of the neighbouring lysil residues Lys 72 or Lys 73 in SL (Lys)-Cyt C on the molecular surface. From the absorbtion and CD-spectra of the modified and native Cyt C in the spectral interval 190--450 nm and from the high resolution PMR data the conclusion has been made that  the chemical modification does not alter the immediate vicinity of the heme group and the molecular structure of Cyt C as a whole. Therefore both SL-modified preparations might be useful for the conformational and functional investigations of Cyt C."}
{"id": "PMID:216911", "title": "Chemical and radiation induced late dominant lethal effects in mice.", "content": "Although theoretically expected, experimental data to date have not shown dominant lethal expression to occur throughout the developmental period. Specifically, late post-implantation effects have not been demonstrated. We routinely use an experimental technique in which parental females mated to mutagenically treated males are allowed to give birth and wean their litter, and their uterine horns are then inspected for uterine scars indicative of live and dead embryos. In a number of experiments in which males were mutagenically treated with either chemicals or X-irradiation, a discrepancy was observed between the number of live embryos as determined by the scar technique and the number of live observed at birth, suggesting the possibility of embryonic losses at a late stage in development. Initial analyses showed that mutagenic treatment increased the percentage of these late losses. These differences were statistically significant in 2 of 3 analyses. Factors affecting statistical significance and an understanding of dominant lethal mutations are discussed.", "contents": "Chemical and radiation induced late dominant lethal effects in mice. Although theoretically expected, experimental data to date have not shown dominant lethal expression to occur throughout the developmental period. Specifically, late post-implantation effects have not been demonstrated. We routinely use an experimental technique in which parental females mated to mutagenically treated males are allowed to give birth and wean their litter, and their uterine horns are then inspected for uterine scars indicative of live and dead embryos. In a number of experiments in which males were mutagenically treated with either chemicals or X-irradiation, a discrepancy was observed between the number of live embryos as determined by the scar technique and the number of live observed at birth, suggesting the possibility of embryonic losses at a late stage in development. Initial analyses showed that mutagenic treatment increased the percentage of these late losses. These differences were statistically significant in 2 of 3 analyses. Factors affecting statistical significance and an understanding of dominant lethal mutations are discussed."}
{"id": "PMID:216912", "title": "Sleep apnea, hypopnea and oxygen desaturation in normal subjects. A strong male predominance.", "content": "Thirty asymptomatic men and 19 asymptomatic women were monitored during one night's sleep to determine the incidence of breathing abnormalities and oxygen desaturation in normal subjects. Twenty men accounted for 264 episodes of nocturnal oxygen desaturation or abnormal breathing. Women never experienced oxygen desaturation, and only three had a total of nine episodes of apnea. These sex differences were highly significant (P less than 0.003). In men, increasing age and obesity correlated positively with the incidence of nocturnal oxygen desaturation and abnormal breathing. Four asymptomatic men weighing more than 90 kg dropped their saturation to very low levels (68 to 72 per cent). Abnormal breathing and oxygen desaturation during sleep in subjects with chronic obstructive lung disease of the syndrome of hypersomnolence with periodic breathing may represent the superimposition of smoking or obesity on a normal tendency to snoring and oxygen desaturation in men.", "contents": "Sleep apnea, hypopnea and oxygen desaturation in normal subjects. A strong male predominance. Thirty asymptomatic men and 19 asymptomatic women were monitored during one night's sleep to determine the incidence of breathing abnormalities and oxygen desaturation in normal subjects. Twenty men accounted for 264 episodes of nocturnal oxygen desaturation or abnormal breathing. Women never experienced oxygen desaturation, and only three had a total of nine episodes of apnea. These sex differences were highly significant (P less than 0.003). In men, increasing age and obesity correlated positively with the incidence of nocturnal oxygen desaturation and abnormal breathing. Four asymptomatic men weighing more than 90 kg dropped their saturation to very low levels (68 to 72 per cent). Abnormal breathing and oxygen desaturation during sleep in subjects with chronic obstructive lung disease of the syndrome of hypersomnolence with periodic breathing may represent the superimposition of smoking or obesity on a normal tendency to snoring and oxygen desaturation in men."}
{"id": "PMID:216913", "title": "Alpha-adrenergic hyper-responsiveness in asthma.", "content": "Because alpha-adrenergic stimulation causes bronchoconstriction, the alpha-adrenergic responsiveness of 21 subjects with allergic asthma was compared with that of 16 subjects with allergic rhinitis and 38 normal control subjects. None of the patients had taken medications for at least 30 days before study. Alpha-adrenergic responsiveness was measured by the capacity of phenylephrine to constrict the cutaneous vascular bed and to dilate the pupillary sphincter muscle. Asthmatic subjects required 4.0 +/- 0.6 ng to reduce their cutaneous blood flow by 50 per cent, whereas normal controls required 32.0 +/- 7.5 ng (P less than 0.005) and subjects with allergic rhinitis required 23.7 +/- 9.4 ng (P less than 0.02). The pupils of asthmatic subjects dilated by greater than 0.5 mm in response to 1.8 +/- 0.14 per cent phenylephrine, patients with allergic rhinitis required 2.4 +/- 0.16 (P less than 0.01), and normal controls needed 2.7 +/- 0.07 (P less than 0.00001). Therefore, the patients with allergic asthma had significantly enhanced alpha-adrenergic responses when compared both to normal subjects and patients with allergic rhinitis; the possibility that increased alpha-adrenergic activity contributes to the asthmatic diathesis warrants further exploration.", "contents": "Alpha-adrenergic hyper-responsiveness in asthma. Because alpha-adrenergic stimulation causes bronchoconstriction, the alpha-adrenergic responsiveness of 21 subjects with allergic asthma was compared with that of 16 subjects with allergic rhinitis and 38 normal control subjects. None of the patients had taken medications for at least 30 days before study. Alpha-adrenergic responsiveness was measured by the capacity of phenylephrine to constrict the cutaneous vascular bed and to dilate the pupillary sphincter muscle. Asthmatic subjects required 4.0 +/- 0.6 ng to reduce their cutaneous blood flow by 50 per cent, whereas normal controls required 32.0 +/- 7.5 ng (P less than 0.005) and subjects with allergic rhinitis required 23.7 +/- 9.4 ng (P less than 0.02). The pupils of asthmatic subjects dilated by greater than 0.5 mm in response to 1.8 +/- 0.14 per cent phenylephrine, patients with allergic rhinitis required 2.4 +/- 0.16 (P less than 0.01), and normal controls needed 2.7 +/- 0.07 (P less than 0.00001). Therefore, the patients with allergic asthma had significantly enhanced alpha-adrenergic responses when compared both to normal subjects and patients with allergic rhinitis; the possibility that increased alpha-adrenergic activity contributes to the asthmatic diathesis warrants further exploration."}
{"id": "PMID:216925", "title": "Bovine virus diarrhea-mucosal disease. II. Isolation and characterization of a cytopathogenic virus and experimental production of the disease.", "content": "A disease broke out in calves in the Tokachi district of Hokkaido. It induced pyrexia, respiratory symptoms, diarrhea, bloody feces, leukopenia, and sometimes erosion of the oral mucous membrane and muzzle. Its morbidity rate was 90% and its fatality rate 50%. Bovine virus diarrhea (BVD) virus was isolated from organs of dead calves and blood and feces of affected calves. It exhibited a cytopathic effect on calf kidney cell culture. Antisera against the Nose and the Oregon C24V strains of BVD virus showed an antibody titer of the same order against the homologous virus and the isolated strain. Antiserum against the isolated strain, however, showed much lower antibody titers against the Nose and the Oregon C24V strains than against the homologous virus. When inoculated with the isolated virus, two calves manifested acute symptoms, but recovered at any rate. One of them, however, suffered again from clinical infection and died eventually 37 days after inoculation. It presented pathological changes closely resembling those of the case of spontaneous infection. Virus was recovered from its principal organs, intestinal canal, and lymph nodes of various regions of the body.", "contents": "Bovine virus diarrhea-mucosal disease. II. Isolation and characterization of a cytopathogenic virus and experimental production of the disease. A disease broke out in calves in the Tokachi district of Hokkaido. It induced pyrexia, respiratory symptoms, diarrhea, bloody feces, leukopenia, and sometimes erosion of the oral mucous membrane and muzzle. Its morbidity rate was 90% and its fatality rate 50%. Bovine virus diarrhea (BVD) virus was isolated from organs of dead calves and blood and feces of affected calves. It exhibited a cytopathic effect on calf kidney cell culture. Antisera against the Nose and the Oregon C24V strains of BVD virus showed an antibody titer of the same order against the homologous virus and the isolated strain. Antiserum against the isolated strain, however, showed much lower antibody titers against the Nose and the Oregon C24V strains than against the homologous virus. When inoculated with the isolated virus, two calves manifested acute symptoms, but recovered at any rate. One of them, however, suffered again from clinical infection and died eventually 37 days after inoculation. It presented pathological changes closely resembling those of the case of spontaneous infection. Virus was recovered from its principal organs, intestinal canal, and lymph nodes of various regions of the body."}
{"id": "PMID:216926", "title": "Inactivated-concentrated virus antigen for indirect complement fixation test of foot-and-mouth disease.", "content": "To the culture fluids of BHK-21 cells infected with each of types O, A, and Asia 1 of foot-and-mouth disease virus was added acetylethyleneimine to 0.05% (v/v). The mixtures were incubated at 37 degrees C for 24 hours. To them were then added polyethylene glycol 6000 to 10% (w/v), and the mixtures concentrated to one-tenth of the initial volume. The resulting inactivated-concentrated virus antigens showed a complement fixation (CF) titer ranging from 12 to 24. The recovery rate of CF activity was 40 approximately 60%. This activity of each antigen was maintained at 4 degrees C or -70 degrees C for 6 months at least. Experimentally infected cattle were examined for the development of antibody by the aid of the indirect complement fixation (ICF) test with those antigens. As a result, ICF antibody began to be detected 3 approximately 5 days after inoculation. Its titer reached a maximum 10 approximately 14 days after inoculation and decreased gradually thereafter. It was detected even 232 days after inoculation. There was a tendency for the development of ICF antibody to be parallel with that of neutralizing antibody. It was suggested that ICF antibody might be type-specific. In conclusion, the antigens prepared had such high activity that they could be used for the determination of antibody by ICF. In addition, they were of great practical value because of their sufficient keeping quality and safety.", "contents": "Inactivated-concentrated virus antigen for indirect complement fixation test of foot-and-mouth disease. To the culture fluids of BHK-21 cells infected with each of types O, A, and Asia 1 of foot-and-mouth disease virus was added acetylethyleneimine to 0.05% (v/v). The mixtures were incubated at 37 degrees C for 24 hours. To them were then added polyethylene glycol 6000 to 10% (w/v), and the mixtures concentrated to one-tenth of the initial volume. The resulting inactivated-concentrated virus antigens showed a complement fixation (CF) titer ranging from 12 to 24. The recovery rate of CF activity was 40 approximately 60%. This activity of each antigen was maintained at 4 degrees C or -70 degrees C for 6 months at least. Experimentally infected cattle were examined for the development of antibody by the aid of the indirect complement fixation (ICF) test with those antigens. As a result, ICF antibody began to be detected 3 approximately 5 days after inoculation. Its titer reached a maximum 10 approximately 14 days after inoculation and decreased gradually thereafter. It was detected even 232 days after inoculation. There was a tendency for the development of ICF antibody to be parallel with that of neutralizing antibody. It was suggested that ICF antibody might be type-specific. In conclusion, the antigens prepared had such high activity that they could be used for the determination of antibody by ICF. In addition, they were of great practical value because of their sufficient keeping quality and safety."}
{"id": "PMID:216927", "title": "Field trials on transmissible gastroenteritis live virus vaccine in newborn piglets.", "content": "Field trials were conducted on attenuated live virus vaccine of transmissible gastroenteritis to confer active immunity to newborn piglets. To examine innocuity and efficacy of the vaccine, a total of 714 newborn piglets were subjected to these trials. Of them, 357 piglets were administered orally with 10(7.0) TCID50 within 3 days after birth, and the other 357 piglets served as nonvaccinated controls. No undesirable postvaccinal reaction was observed in any vaccinated piglet. Suckling piglets born from nonimmune sows showed a good antibody response after vaccination. They were different, however, in antibody titer from one experimental place to another. Antibody levels were high in piglets raised in the northern experimental places. On the contrary, the antibody response of suckling piglets born from immune sows was influenced by vaccination. In most of these piglets, antibody titers declined markedly and disappeared finally 3 months after vaccination. About 25% of the non-vaccinated piglets showed an antibody response by pen contact with vaccinated ones.", "contents": "Field trials on transmissible gastroenteritis live virus vaccine in newborn piglets. Field trials were conducted on attenuated live virus vaccine of transmissible gastroenteritis to confer active immunity to newborn piglets. To examine innocuity and efficacy of the vaccine, a total of 714 newborn piglets were subjected to these trials. Of them, 357 piglets were administered orally with 10(7.0) TCID50 within 3 days after birth, and the other 357 piglets served as nonvaccinated controls. No undesirable postvaccinal reaction was observed in any vaccinated piglet. Suckling piglets born from nonimmune sows showed a good antibody response after vaccination. They were different, however, in antibody titer from one experimental place to another. Antibody levels were high in piglets raised in the northern experimental places. On the contrary, the antibody response of suckling piglets born from immune sows was influenced by vaccination. In most of these piglets, antibody titers declined markedly and disappeared finally 3 months after vaccination. About 25% of the non-vaccinated piglets showed an antibody response by pen contact with vaccinated ones."}
{"id": "PMID:216929", "title": "Computer simulation of Gumboro disease outbreak. II. Results obtained with models G-1 and G-2.", "content": "The authors conducted a computer simulation with their Models G-1 and G-2 for Gumboro disease ten times in each of the following initial conditions: (1) size of population, 50, 100, and 1,000 chickens; (2) age of housing, 1, 7, 14, and 21 days; (3) nine levels of parentally conferred immunity in one-day-old chicks; (4) four levels of virus contamination; and (5) three steps of coefficient for aggravating morbid status. Every simulation was operated up to the age when all the birds of a flock turned to be insusceptible so as to yield the daily numbers of chickens (1) susceptible, (2) diseased, (3) immunized, and (4) removed, and (5) the accumulation of diseased chickens. The innate resistance, parentally conferred immunity, virus contamination, and morbid status were expressed in such values that they could be compared with one another. As a result, Model G-2 produced a more realistic epizootic pattern than Model G-1, but both models concealed the effect of differences in size of population and in age of housing. Notwithstanding the incompleteness of the models, the computer simulation gave valuable information for a further advancement in this series of studies.", "contents": "Computer simulation of Gumboro disease outbreak. II. Results obtained with models G-1 and G-2. The authors conducted a computer simulation with their Models G-1 and G-2 for Gumboro disease ten times in each of the following initial conditions: (1) size of population, 50, 100, and 1,000 chickens; (2) age of housing, 1, 7, 14, and 21 days; (3) nine levels of parentally conferred immunity in one-day-old chicks; (4) four levels of virus contamination; and (5) three steps of coefficient for aggravating morbid status. Every simulation was operated up to the age when all the birds of a flock turned to be insusceptible so as to yield the daily numbers of chickens (1) susceptible, (2) diseased, (3) immunized, and (4) removed, and (5) the accumulation of diseased chickens. The innate resistance, parentally conferred immunity, virus contamination, and morbid status were expressed in such values that they could be compared with one another. As a result, Model G-2 produced a more realistic epizootic pattern than Model G-1, but both models concealed the effect of differences in size of population and in age of housing. Notwithstanding the incompleteness of the models, the computer simulation gave valuable information for a further advancement in this series of studies."}
{"id": "PMID:216931", "title": "Solubilization of a mammalian beta-adrenergic receptor.", "content": "Binding sites for iodohydroxybenzylpindolol with characteristics of a beta2-adrenergic receptor have been identified in a crude membrane fraction from guinea-pig lung. The binding sites could be solubilized by treatment of the membrane fraction with digitonin. Upon solubilization receptors retain their beta2-adrenergic type as indicated by the rank order of potencies of agonists in binding-inhibition experiments. The solubilized receptors demonstrate a marked increase in affinity for agonists compared with particulate receptors whereas antagonist affinity remains unchanged. Solubilized receptors are insensitive to divalent cations (Mg2+, Mn2+, Ca 2+) which increase the potency of agonists for particulate receptors. The effects of Mg2+ can be reversed by Gpp(NH)p in particulate preparations; Gpp(NH)p is ineffective for the solubilized preparation. These experiments establish that beta-adrenergic receptors can be solubilized even from crude mammalian membrane preparations. They also show that the mammalian beta-adrenergic receptor in situ is under constraints with respect to agonist affinity and is modulated by divalent cations and guanyl nucleotides in the intact membrane.", "contents": "Solubilization of a mammalian beta-adrenergic receptor. Binding sites for iodohydroxybenzylpindolol with characteristics of a beta2-adrenergic receptor have been identified in a crude membrane fraction from guinea-pig lung. The binding sites could be solubilized by treatment of the membrane fraction with digitonin. Upon solubilization receptors retain their beta2-adrenergic type as indicated by the rank order of potencies of agonists in binding-inhibition experiments. The solubilized receptors demonstrate a marked increase in affinity for agonists compared with particulate receptors whereas antagonist affinity remains unchanged. Solubilized receptors are insensitive to divalent cations (Mg2+, Mn2+, Ca 2+) which increase the potency of agonists for particulate receptors. The effects of Mg2+ can be reversed by Gpp(NH)p in particulate preparations; Gpp(NH)p is ineffective for the solubilized preparation. These experiments establish that beta-adrenergic receptors can be solubilized even from crude mammalian membrane preparations. They also show that the mammalian beta-adrenergic receptor in situ is under constraints with respect to agonist affinity and is modulated by divalent cations and guanyl nucleotides in the intact membrane."}
{"id": "PMID:216932", "title": "Correlation between the effects of salbutamol on contractions and cyclic AMP content of isolated fast-and slow-contracting muscles of the guinea pig.", "content": "The effects of isoprenaline and salbutamol on incomplete tetanic contractions of the isolated soleus (slow contracting) and extensor digitorum longus (EDL-fast-contracting) muscles of the guinea pig were studied and an attempt made to correlate these effects on contractility with changes in cyclic AMP concentrations. Salbutamol was 10-12 times less potent than (+/-)isoprenaline in decreasing the force of subtetanic contractions in the soleus and between 5-6 times less potent in increasing the force of subtetanic contractions in the EDL. This observation plus the lack of activity of both the selective beta1-adrenoceptor antagonist (atenolol) and the selective beta1 agonist (H 133/22) in the EDL implies involvement of beta2-adrenoceptors in these responses of the muscles to isoprenaline and salbutamol. The soleus muscle was about 6-12 times more sensitive to effects of beta-adrenoceptor agonists than the EDL. In concentrations which produced effects on muscle contractility, salbutamol significantly elevated cyclic AMP concentrations in both types of muscle. These effects were antagonised by propranolol. It seems clear that the contrasting effects of sympathomimetic amines on slow-and fast contracting muscle are mediated through a common mechanism-elevation of cyclic AMP. Possible explanations of this apparent paradox are discussed.", "contents": "Correlation between the effects of salbutamol on contractions and cyclic AMP content of isolated fast-and slow-contracting muscles of the guinea pig. The effects of isoprenaline and salbutamol on incomplete tetanic contractions of the isolated soleus (slow contracting) and extensor digitorum longus (EDL-fast-contracting) muscles of the guinea pig were studied and an attempt made to correlate these effects on contractility with changes in cyclic AMP concentrations. Salbutamol was 10-12 times less potent than (+/-)isoprenaline in decreasing the force of subtetanic contractions in the soleus and between 5-6 times less potent in increasing the force of subtetanic contractions in the EDL. This observation plus the lack of activity of both the selective beta1-adrenoceptor antagonist (atenolol) and the selective beta1 agonist (H 133/22) in the EDL implies involvement of beta2-adrenoceptors in these responses of the muscles to isoprenaline and salbutamol. The soleus muscle was about 6-12 times more sensitive to effects of beta-adrenoceptor agonists than the EDL. In concentrations which produced effects on muscle contractility, salbutamol significantly elevated cyclic AMP concentrations in both types of muscle. These effects were antagonised by propranolol. It seems clear that the contrasting effects of sympathomimetic amines on slow-and fast contracting muscle are mediated through a common mechanism-elevation of cyclic AMP. Possible explanations of this apparent paradox are discussed."}
{"id": "PMID:216936", "title": "Alterations in surface proteins of rat cells transformed by avian sarcoma virus B77.", "content": "Cell membrane proteins of avian sarcoma virus B77V--transformed cells LWF B55 and LWF B77 and uninfected rat embryo fibroblasts were analyzed by SDS acrylamide gel electrophoresis. Following alterations in cell surface proteins of LWF B55 and LWF B77 cells were found: one, a slight decrease of two high molecular weight proteins the larger of which corresponds presumably to \"LETS\" protein and a decrease of a protein with approximative molecular weight 50 000; two, increase in content of proteins with molecular weight of about 90--95 000 and 70--75 000 as well as a marked increase of a protein with molecular weight of 30--35 000.", "contents": "Alterations in surface proteins of rat cells transformed by avian sarcoma virus B77. Cell membrane proteins of avian sarcoma virus B77V--transformed cells LWF B55 and LWF B77 and uninfected rat embryo fibroblasts were analyzed by SDS acrylamide gel electrophoresis. Following alterations in cell surface proteins of LWF B55 and LWF B77 cells were found: one, a slight decrease of two high molecular weight proteins the larger of which corresponds presumably to \"LETS\" protein and a decrease of a protein with approximative molecular weight 50 000; two, increase in content of proteins with molecular weight of about 90--95 000 and 70--75 000 as well as a marked increase of a protein with molecular weight of 30--35 000."}
{"id": "PMID:216937", "title": "Collagenolytic activity in leukocytes isolated from patients with leukemias and Hodgkin's disease.", "content": "Collagenolytic activity in leukocytes and plasma concentration of hydroxyproline were estimated in 80 patients with leukemias and Hodgkin's disease and in 20 healthy individuals. An increase of both studied parameters was found in chronic myelocytic leukemia and Hodgkin's disease, and a decrease was shown in acute myelocytic leukemia and acute lymphatic leukemia. The results obtained imply that metabolic changes occur in leukemia leukocytes, and indicate the presence of disturbances in the metabolism of connective tissue in the studied disorders.", "contents": "Collagenolytic activity in leukocytes isolated from patients with leukemias and Hodgkin's disease. Collagenolytic activity in leukocytes and plasma concentration of hydroxyproline were estimated in 80 patients with leukemias and Hodgkin's disease and in 20 healthy individuals. An increase of both studied parameters was found in chronic myelocytic leukemia and Hodgkin's disease, and a decrease was shown in acute myelocytic leukemia and acute lymphatic leukemia. The results obtained imply that metabolic changes occur in leukemia leukocytes, and indicate the presence of disturbances in the metabolism of connective tissue in the studied disorders."}
{"id": "PMID:216941", "title": "Peripheral motor nerve conduction velocities in children undergoing chronic hemodialysis.", "content": "Peroneal motor nerve conduction velocities (MNCVs) were performed on 58 children aged 20 months to 12 years undergoing chronic hemodialysis. No patient had any clinical manifestations of uremic polyneuropathy. The mean MNCV in 21 children at the onset of dialysis was 42.0 m/sec; significantly slower than the control group of 51.4 +/- 5.3 m/sec (p less than 0.001). 16 studied performed between the 1st and 6th month had a mean MNCV of 43.2 +/- 5.7 m/sec, also slower than the normal controls (p less than 0.001). We conclude that peroneal MNCVs are reduced in most children at the initiation of chronic hemodialysis and do not change significantly during the next 6--12 months and that the routine practice of obtaining such studied is of no value in the clinical management of children undergoing chronic hemodialysis.", "contents": "Peripheral motor nerve conduction velocities in children undergoing chronic hemodialysis. Peroneal motor nerve conduction velocities (MNCVs) were performed on 58 children aged 20 months to 12 years undergoing chronic hemodialysis. No patient had any clinical manifestations of uremic polyneuropathy. The mean MNCV in 21 children at the onset of dialysis was 42.0 m/sec; significantly slower than the control group of 51.4 +/- 5.3 m/sec (p less than 0.001). 16 studied performed between the 1st and 6th month had a mean MNCV of 43.2 +/- 5.7 m/sec, also slower than the normal controls (p less than 0.001). We conclude that peroneal MNCVs are reduced in most children at the initiation of chronic hemodialysis and do not change significantly during the next 6--12 months and that the routine practice of obtaining such studied is of no value in the clinical management of children undergoing chronic hemodialysis."}
{"id": "PMID:216942", "title": "Exaggerated natriuresis in ACTH hypertension in sheep.", "content": "Adrenocorticotrophic hormone (ACTH) administration to sheep (100 IU/day) produces a sustained increase in arterial pressure within 24 h. The effect of ACTH on excretion of an intravenous saline load was tested in 8 adult cross-bred Merino ewes. A significant diuretic response to saline loading was found after 24 h but no increased natriuresis. On days 3 and 6, diuretic and natriuretic responses were both significantly increased. Steroid-induced sodium retention may have abolished the natriuretic effect on day 1.", "contents": "Exaggerated natriuresis in ACTH hypertension in sheep. Adrenocorticotrophic hormone (ACTH) administration to sheep (100 IU/day) produces a sustained increase in arterial pressure within 24 h. The effect of ACTH on excretion of an intravenous saline load was tested in 8 adult cross-bred Merino ewes. A significant diuretic response to saline loading was found after 24 h but no increased natriuresis. On days 3 and 6, diuretic and natriuretic responses were both significantly increased. Steroid-induced sodium retention may have abolished the natriuretic effect on day 1."}
{"id": "PMID:216944", "title": "Nephritogenic glycoprotein. VIII. Demonstration of the limited role of immune complex mechanism for the production of membranous glomerulonephritis.", "content": "Proliferative glomerulonephritis was induced in rats by a single injection in the hind footpads of the glycoprotein isolated from pronase digests of homologous renal cortex, in spite of the evidence that the glycoprotein no longer possessed the antigenic activity with respect to producing the nephrotoxic antibody. In rats given the glycoprotein (without trichloroacetic acid (TCA) treatment) prepared from pronase digests of homologous renal cortex, morphologic changes of proliferative glomerulonephritis were followed (3--4 months after injection) by those of typical membranous glomerulonephritis with an immunofluorescent 'granular' pattern, but in animals which received the glycoprotein (with TCA treatment), the morphologic changes of the kidney were those of proliferative glomerulonephritis with an immunofluorescent 'mesangial' pattern throughout the whole course. Morphologic changes of membranous glomerulonephritis induced in the group given the glycoprotein (without TCA treatment) can be explained by an immune-complex mechanism, superimposed on the basic pathogenesis (common to both groups) of proliferative glomerulonephritis with immunofluorescent 'mesangial' pattern.", "contents": "Nephritogenic glycoprotein. VIII. Demonstration of the limited role of immune complex mechanism for the production of membranous glomerulonephritis. Proliferative glomerulonephritis was induced in rats by a single injection in the hind footpads of the glycoprotein isolated from pronase digests of homologous renal cortex, in spite of the evidence that the glycoprotein no longer possessed the antigenic activity with respect to producing the nephrotoxic antibody. In rats given the glycoprotein (without trichloroacetic acid (TCA) treatment) prepared from pronase digests of homologous renal cortex, morphologic changes of proliferative glomerulonephritis were followed (3--4 months after injection) by those of typical membranous glomerulonephritis with an immunofluorescent 'granular' pattern, but in animals which received the glycoprotein (with TCA treatment), the morphologic changes of the kidney were those of proliferative glomerulonephritis with an immunofluorescent 'mesangial' pattern throughout the whole course. Morphologic changes of membranous glomerulonephritis induced in the group given the glycoprotein (without TCA treatment) can be explained by an immune-complex mechanism, superimposed on the basic pathogenesis (common to both groups) of proliferative glomerulonephritis with immunofluorescent 'mesangial' pattern."}
{"id": "PMID:216945", "title": "Studies on ATP: thiamine diphosphate phosphotransferase activity in rat brain.", "content": "The experiments described in this paper serve as a contribution to the solution of the discrepancies which exist in the assay of ATP:thiamine diphosphate phosphotransferase activity (EC 2.7.4.15), presently in use as a tool for the diagnosis of Leigh's disease (SNE, subacute necrotizing encephalomyelopathy). The results obtained with this phosphotransferase assay can, in part, be explained by the presence of thiamine triphosphate (ThTP) in the preparation of thiamine diphosphate (ThDP) used as a substrate, by the inhibition by ATP of the ThTP phosphohydrolase activity, present in fractions of rat brain homogenates, and by the stimulation by ThDP of the ATPase activity. When [2(-14)C-thiazole]thiamine was used for the synthesis of [14C]ThTP in fractions of rat brain, it was found that after chromatographic separation of thiamine and its phosphates, 14C radioactivity could be demonstrated in the ThTP fractions, even in the absence of an enzyme source. Probably a complex is formed between [14C]thiamine and a phosphate ester which behaves chromatographically as ThTP. It is concluded that the assay system for the measurement of ThTP synthesis in its present form is, in our hands, not suitable for diagnostic purposes.", "contents": "Studies on ATP: thiamine diphosphate phosphotransferase activity in rat brain. The experiments described in this paper serve as a contribution to the solution of the discrepancies which exist in the assay of ATP:thiamine diphosphate phosphotransferase activity (EC 2.7.4.15), presently in use as a tool for the diagnosis of Leigh's disease (SNE, subacute necrotizing encephalomyelopathy). The results obtained with this phosphotransferase assay can, in part, be explained by the presence of thiamine triphosphate (ThTP) in the preparation of thiamine diphosphate (ThDP) used as a substrate, by the inhibition by ATP of the ThTP phosphohydrolase activity, present in fractions of rat brain homogenates, and by the stimulation by ThDP of the ATPase activity. When [2(-14)C-thiazole]thiamine was used for the synthesis of [14C]ThTP in fractions of rat brain, it was found that after chromatographic separation of thiamine and its phosphates, 14C radioactivity could be demonstrated in the ThTP fractions, even in the absence of an enzyme source. Probably a complex is formed between [14C]thiamine and a phosphate ester which behaves chromatographically as ThTP. It is concluded that the assay system for the measurement of ThTP synthesis in its present form is, in our hands, not suitable for diagnostic purposes."}
{"id": "PMID:216946", "title": "Regulation of (Na+, K+) adenosinetriphosphatase of nerve ending membranes: action of norepinephrine and a soluble factor.", "content": "Norepinephrine added in vitro to nerve ending membranes from rat cerebral cortex stimulates the activity of (Na+, K+) adenosinetriphosphatase (ATPase) only in the presence of the soluble brain fraction. In its absence norepinephrine inhibits the enzyme. (Mg2+)ATPase also showed stimulation by norepinephrine in the presence of the soluble fraction, but of lesser magnitude. The activation of (Na+, K+)ATPase by norepinephrine is not reproduced by cyclic AMP and is not antagonized by either alpha- or beta-adrenergic blocking agents. These results suggest that the stimulation caused by norepinephrine is a direct effect on the enzyme and is not mediated by cyclic AMP or adrenergic receptors.", "contents": "Regulation of (Na+, K+) adenosinetriphosphatase of nerve ending membranes: action of norepinephrine and a soluble factor. Norepinephrine added in vitro to nerve ending membranes from rat cerebral cortex stimulates the activity of (Na+, K+) adenosinetriphosphatase (ATPase) only in the presence of the soluble brain fraction. In its absence norepinephrine inhibits the enzyme. (Mg2+)ATPase also showed stimulation by norepinephrine in the presence of the soluble fraction, but of lesser magnitude. The activation of (Na+, K+)ATPase by norepinephrine is not reproduced by cyclic AMP and is not antagonized by either alpha- or beta-adrenergic blocking agents. These results suggest that the stimulation caused by norepinephrine is a direct effect on the enzyme and is not mediated by cyclic AMP or adrenergic receptors."}
{"id": "PMID:216947", "title": "Selective changes in the phosphorylation of endogenous proteins in subcellular fractions from cyclic AMP-induced differentiated neuroblastoma cells.", "content": "The endogenous phosphorylation of specific proteins was studied in subcellular fractions from proliferating and cAMP-induced differentiated neuroblastoma cells. Fractions containing nuclear, membrane-bound, and cytosolic proteins were incubated with [gamma-32P]ATP, in the presence and absence of added cyclic nucleotides. Phosphate incorporation into specific proteins was determined by slab-gel electrophoresis of sodium dodecyl sulfate-solubilized reaction products. Cytosol fractions from differentiated cells demonstrated a twofold increase in cAMP-dependent phosphorylation of a specific protein with apparent mol wt of 59,000 daltons and a comparable decrease in cAMP-independent phosphorylation of another protein (97,000). The nuclear fraction of differentiated cells showed an increase in the cAMP-independent phosphorylation of two nonhistone proteins (110,000 and 102,000). Membrane fractions from differentiated cells exhibited a differential decrease in endogenous phosphorylation of specific proteins. Selective alterations in the phosphorylation of specific proteins in various subcellular components may be important biochemical events associated with the increased levels of differentiated functions in neuroblastoma cells in culture.", "contents": "Selective changes in the phosphorylation of endogenous proteins in subcellular fractions from cyclic AMP-induced differentiated neuroblastoma cells. The endogenous phosphorylation of specific proteins was studied in subcellular fractions from proliferating and cAMP-induced differentiated neuroblastoma cells. Fractions containing nuclear, membrane-bound, and cytosolic proteins were incubated with [gamma-32P]ATP, in the presence and absence of added cyclic nucleotides. Phosphate incorporation into specific proteins was determined by slab-gel electrophoresis of sodium dodecyl sulfate-solubilized reaction products. Cytosol fractions from differentiated cells demonstrated a twofold increase in cAMP-dependent phosphorylation of a specific protein with apparent mol wt of 59,000 daltons and a comparable decrease in cAMP-independent phosphorylation of another protein (97,000). The nuclear fraction of differentiated cells showed an increase in the cAMP-independent phosphorylation of two nonhistone proteins (110,000 and 102,000). Membrane fractions from differentiated cells exhibited a differential decrease in endogenous phosphorylation of specific proteins. Selective alterations in the phosphorylation of specific proteins in various subcellular components may be important biochemical events associated with the increased levels of differentiated functions in neuroblastoma cells in culture."}
{"id": "PMID:216950", "title": "The transcerebral arteries. A postmortem arteriographic study.", "content": "For precise interpretation of CT brain scan and magnification angiography, an in-depth knowledge of the arteries of the white substance is necessary. Postmortem arteriographic studies on a large series of brains provide us with significant information about morphologic as well as pathological changes, of which a few interesting aspects are elucidated.", "contents": "The transcerebral arteries. A postmortem arteriographic study. For precise interpretation of CT brain scan and magnification angiography, an in-depth knowledge of the arteries of the white substance is necessary. Postmortem arteriographic studies on a large series of brains provide us with significant information about morphologic as well as pathological changes, of which a few interesting aspects are elucidated."}
{"id": "PMID:216949", "title": "Effect of experimentally induced generalized seizures on the wakefulness--sleep cycle.", "content": "The effect of experimentally induced generalized seizures on the relations between the various phases of sleep in the wakefulness--sleep cycle was studied in cats with chronically implanted electrodes. After generalized convulsions induced by electrical stimulation of the dorsal hippocampus, unlike those of amygdalar origin, clearly defined changes were observed in the structure of the wakefulness--sleep cycle. In the postseizure period, with increasing wakefulness sharp depression of paradoxical sleep takes place. However, in slow wave sleep only slight changes were observed. Instead of a rebound phenomenon, paradoxical sleep was sharply induced in cats after preliminary deprivation of paradoxical sleep as a result of generalized seizures induced by electrical stimulation of the neocortex. Nonspecific hyperactivation of the brain, in the form of epileptiform discharges, thus has a particularly marked effect on the structure of paradoxical sleep.", "contents": "Effect of experimentally induced generalized seizures on the wakefulness--sleep cycle. The effect of experimentally induced generalized seizures on the relations between the various phases of sleep in the wakefulness--sleep cycle was studied in cats with chronically implanted electrodes. After generalized convulsions induced by electrical stimulation of the dorsal hippocampus, unlike those of amygdalar origin, clearly defined changes were observed in the structure of the wakefulness--sleep cycle. In the postseizure period, with increasing wakefulness sharp depression of paradoxical sleep takes place. However, in slow wave sleep only slight changes were observed. Instead of a rebound phenomenon, paradoxical sleep was sharply induced in cats after preliminary deprivation of paradoxical sleep as a result of generalized seizures induced by electrical stimulation of the neocortex. Nonspecific hyperactivation of the brain, in the form of epileptiform discharges, thus has a particularly marked effect on the structure of paradoxical sleep."}
{"id": "PMID:216955", "title": "[Surgery of endocrine pancreatic tumors. Results of a survey in the German Federal Republic].", "content": "Within a ten-year scan (1967-1976) 207 insulinomas, 50 gastrinomas, 8 Verner-Morrison tumours, 5 glucagonomas and 12 endocrine pancreatic tumours with associated MEA syndrome (multiple endocrine adenomatosis) were treated surgically at  various university hospitals (information obtained by questionnaire). Half of the insulinomas were treated by enucleation, one third by resection of the tail of the pancreas. Total gastrectomy was the procedure of choice in 80% of patients with gastrinoma, but sometimes pancreatic resection to remove the tumour was added. An new therapeutic concept of using histamine-H2 receptor antagonists for treating patients with Zollinger-Ellison syndrome is discussed. In the eight patients with a Verner-Morrison syndrome removal of the tumour or distal pancreatic resection was the procedure of choice.", "contents": "[Surgery of endocrine pancreatic tumors. Results of a survey in the German Federal Republic]. Within a ten-year scan (1967-1976) 207 insulinomas, 50 gastrinomas, 8 Verner-Morrison tumours, 5 glucagonomas and 12 endocrine pancreatic tumours with associated MEA syndrome (multiple endocrine adenomatosis) were treated surgically at  various university hospitals (information obtained by questionnaire). Half of the insulinomas were treated by enucleation, one third by resection of the tail of the pancreas. Total gastrectomy was the procedure of choice in 80% of patients with gastrinoma, but sometimes pancreatic resection to remove the tumour was added. An new therapeutic concept of using histamine-H2 receptor antagonists for treating patients with Zollinger-Ellison syndrome is discussed. In the eight patients with a Verner-Morrison syndrome removal of the tumour or distal pancreatic resection was the procedure of choice."}
{"id": "PMID:216959", "title": "Germ cell malignancies of the ovary.", "content": "Historically, ovarian germ cell malignancies carry a very poor prognosis. The use of surgery alone or in combination with radiation therapy does not appreciably increase survival. The combination of surgery, chemotherapy, and, in some instances, radiation therapy has accounted for an 89% two-year survival in 26 patients with germ cell malignancies of the ovary exclusive of \"pure\" dysgerminoma. Short-term chemotherapy appears as effective as the long-term therapy advocated by other investigators.", "contents": "Germ cell malignancies of the ovary. Historically, ovarian germ cell malignancies carry a very poor prognosis. The use of surgery alone or in combination with radiation therapy does not appreciably increase survival. The combination of surgery, chemotherapy, and, in some instances, radiation therapy has accounted for an 89% two-year survival in 26 patients with germ cell malignancies of the ovary exclusive of \"pure\" dysgerminoma. Short-term chemotherapy appears as effective as the long-term therapy advocated by other investigators."}
{"id": "PMID:216960", "title": "Pelvic mass presenting as meralgia paresthetica.", "content": "A 40-year-old woman presented to her gynecologist with an apparent unilateral neuropathy of the lateral cutaneous femoral nerve of the thigh (meralgia paresthetica). On examination, the sensory disturbance extended outside the usual distribution of the lateral femoral cutaneous nerve, suggesting a more proximal lumbar plexus involvement. She was subsequently found to have uterine fibroid disease. At the time of surgery a large posteriorly situated uterine mass was noted to compress the superior portion of the lumbar plexus. Following surgery, she has been symptom-free.", "contents": "Pelvic mass presenting as meralgia paresthetica. A 40-year-old woman presented to her gynecologist with an apparent unilateral neuropathy of the lateral cutaneous femoral nerve of the thigh (meralgia paresthetica). On examination, the sensory disturbance extended outside the usual distribution of the lateral femoral cutaneous nerve, suggesting a more proximal lumbar plexus involvement. She was subsequently found to have uterine fibroid disease. At the time of surgery a large posteriorly situated uterine mass was noted to compress the superior portion of the lumbar plexus. Following surgery, she has been symptom-free."}
{"id": "PMID:216962", "title": "Dysplastic enamel in odontomas.", "content": "A series of odontomas was studied by light microscopy, with special emphasis on abnormal enamel in these lesions. The findings were compared to those in amelogenesis imperfecta and in other conditions in which abnormal enamel is found. It was concluded that dysplastic enamel exhibits a number of appearances which are described in this article. A strongly basophilic laminated material was also found, often covering prismatic enamel, but it did not itself appear to be a form of enamel; its identity is not clear. Odontomas, being readily available, offer a good opportunity to study dysplastic enamel.", "contents": "Dysplastic enamel in odontomas. A series of odontomas was studied by light microscopy, with special emphasis on abnormal enamel in these lesions. The findings were compared to those in amelogenesis imperfecta and in other conditions in which abnormal enamel is found. It was concluded that dysplastic enamel exhibits a number of appearances which are described in this article. A strongly basophilic laminated material was also found, often covering prismatic enamel, but it did not itself appear to be a form of enamel; its identity is not clear. Odontomas, being readily available, offer a good opportunity to study dysplastic enamel."}
{"id": "PMID:216963", "title": "Ultrastructure of mucoepidermoid carcinoma in minor salivary glands.", "content": "Three cases of mucoepidermoid carcinoma of minor salivary glands were studied by electron microscopy. Mucus-secreting cells contained numerous mucous globules and bundles of fine cytoplasmic filaments. Another cell type contained a large number of glycogen particles, akin to tumor cells in glycogen-rich adenocarcinoma, and it is postulated that these cells represent the intermediate cells observed by light microscopy. Epidermoid cells contained a moderate amount of tonofilaments and various numbers of organelles. Mucus-secreting and epidermoid cells that surrounded a cystic space exhibited many microvilli. Results of this study support the theory that mucoepidermoid carcinoma develops from salivary gland duct cells with different cellular differentiation potentials and, in general, agree with the conventional grading system of mucoepidermoid carcinoma.", "contents": "Ultrastructure of mucoepidermoid carcinoma in minor salivary glands. Three cases of mucoepidermoid carcinoma of minor salivary glands were studied by electron microscopy. Mucus-secreting cells contained numerous mucous globules and bundles of fine cytoplasmic filaments. Another cell type contained a large number of glycogen particles, akin to tumor cells in glycogen-rich adenocarcinoma, and it is postulated that these cells represent the intermediate cells observed by light microscopy. Epidermoid cells contained a moderate amount of tonofilaments and various numbers of organelles. Mucus-secreting and epidermoid cells that surrounded a cystic space exhibited many microvilli. Results of this study support the theory that mucoepidermoid carcinoma develops from salivary gland duct cells with different cellular differentiation potentials and, in general, agree with the conventional grading system of mucoepidermoid carcinoma."}
{"id": "PMID:216964", "title": "Gingival metastasis from primary hepatocellular carcinoma. Report of a case.", "content": "A case of primary hepatocellular carcinoma metastatic to the gingiva is described. Hepatocellular carcinoma is an uncommon malignancy, generally occurring in a cirrhotic liver, which rarely metastasizes to the maxillofacial area. Of eight such cases in the English-language literature, the present case is the fourth involving metastasis to the gingiva. Hepatocellular carcinoma would seem to metastasize with equal frequency to the gingiva and to the mandibular bone. In the case described, histologic examination of the gingival lesion definitively established the diagnosis following somewhat equivocal results of needle biopsy of the liver.", "contents": "Gingival metastasis from primary hepatocellular carcinoma. Report of a case. A case of primary hepatocellular carcinoma metastatic to the gingiva is described. Hepatocellular carcinoma is an uncommon malignancy, generally occurring in a cirrhotic liver, which rarely metastasizes to the maxillofacial area. Of eight such cases in the English-language literature, the present case is the fourth involving metastasis to the gingiva. Hepatocellular carcinoma would seem to metastasize with equal frequency to the gingiva and to the mandibular bone. In the case described, histologic examination of the gingival lesion definitively established the diagnosis following somewhat equivocal results of needle biopsy of the liver."}
{"id": "PMID:216965", "title": "[Diagnosis and therapy of Wilms' tumor based on a survey of 16 children with nephroblastoma].", "content": "On the second place in malignant diseases of children, after the leukemias, we could find the Wilms-Tumor. Of the 16 children we treated in the years from 1965 to 1977, 8 children died, 2 patients couldn't be any longer observed and 6 patients are still alive. 5 children of these have obtained now a relapse-free survival from 1 year and 2 months to 2 years and 7 months. We could see, that the prognosis depends only on the stage of the tumor and not on the age of patients. On 3 cases we will try to show, how difficult the diagnosis of the Wilms-Tumor is and how important it is, to treat resolutely pulmonary and liver metastases. As diagnostic methods were used i. v. P., the sonography and the selective renalangiography. Since 1976 our treatment consists of preoperative irradiation of tumors, nephrectomy, postoperative irradiation of tumor-bed and adjuvant chemotherapy (actinomycin D, vincristine and adriamycin). Pulmonary and liver metastases are a domain for chemotherapy, combined with irradiation (danger of pneumonitis and toxic hepatitis) and eventually a resection is necessary. Only the good cooperation of an oncologic team could achieve an improvement of the cure rate of this tumor, as we know from the American countries (survival 75%).", "contents": "[Diagnosis and therapy of Wilms' tumor based on a survey of 16 children with nephroblastoma]. On the second place in malignant diseases of children, after the leukemias, we could find the Wilms-Tumor. Of the 16 children we treated in the years from 1965 to 1977, 8 children died, 2 patients couldn't be any longer observed and 6 patients are still alive. 5 children of these have obtained now a relapse-free survival from 1 year and 2 months to 2 years and 7 months. We could see, that the prognosis depends only on the stage of the tumor and not on the age of patients. On 3 cases we will try to show, how difficult the diagnosis of the Wilms-Tumor is and how important it is, to treat resolutely pulmonary and liver metastases. As diagnostic methods were used i. v. P., the sonography and the selective renalangiography. Since 1976 our treatment consists of preoperative irradiation of tumors, nephrectomy, postoperative irradiation of tumor-bed and adjuvant chemotherapy (actinomycin D, vincristine and adriamycin). Pulmonary and liver metastases are a domain for chemotherapy, combined with irradiation (danger of pneumonitis and toxic hepatitis) and eventually a resection is necessary. Only the good cooperation of an oncologic team could achieve an improvement of the cure rate of this tumor, as we know from the American countries (survival 75%)."}
{"id": "PMID:216966", "title": "Evidence that raphe-spinal neurons mediate opiate and midbrain stimulation-produced analgesias.", "content": "The present experiments were undertaken to assess the role of neurons in the nucleus raphe magnus (NRM) in mediating opiate and stimulation-produced analgesias. A cannode for both electric stimulation and local opiate microinjection was placed in the midbrain preiaqueductal gray region of decerebrate or chloralose-urethane anesthetized cats. Microelectrodes recorded the responses of medullary NRM neurons. Raphe-spinal neurons were identified by antidromic activation from the cerevical spinal cord. Fifteen of 20 raphe-spinal cells tested were excited by electrical stimulation of the midbrain. Of 49 NRM neurons tested, 26 were excited by either systemic or midbrain injection of opiate agonist. Twelve of 33 NRM cells tested by midbrain microinjection were excited. In 10 the effect was reversed by naloxone. Seventeen raphe-spinal neurons were tested; 5 showed naloxone-reversible excitation to either midbrain or intravenous injection of opiates. NRM neurons respond to auditory and somatic stimuli; at least half respond maximally to somatic stimuli of noxious intensity. These findings are consistent with the hypothesis that the raphe-spinal projection mediates opiate and electrical stimulation-produced effects from midbrain sites. The properties of raphe-spinal neurons suggest that they are part of a negative feedback system which monitors and limits the output of spinal dorsal horn pain-transmission neurons.", "contents": "Evidence that raphe-spinal neurons mediate opiate and midbrain stimulation-produced analgesias. The present experiments were undertaken to assess the role of neurons in the nucleus raphe magnus (NRM) in mediating opiate and stimulation-produced analgesias. A cannode for both electric stimulation and local opiate microinjection was placed in the midbrain preiaqueductal gray region of decerebrate or chloralose-urethane anesthetized cats. Microelectrodes recorded the responses of medullary NRM neurons. Raphe-spinal neurons were identified by antidromic activation from the cerevical spinal cord. Fifteen of 20 raphe-spinal cells tested were excited by electrical stimulation of the midbrain. Of 49 NRM neurons tested, 26 were excited by either systemic or midbrain injection of opiate agonist. Twelve of 33 NRM cells tested by midbrain microinjection were excited. In 10 the effect was reversed by naloxone. Seventeen raphe-spinal neurons were tested; 5 showed naloxone-reversible excitation to either midbrain or intravenous injection of opiates. NRM neurons respond to auditory and somatic stimuli; at least half respond maximally to somatic stimuli of noxious intensity. These findings are consistent with the hypothesis that the raphe-spinal projection mediates opiate and electrical stimulation-produced effects from midbrain sites. The properties of raphe-spinal neurons suggest that they are part of a negative feedback system which monitors and limits the output of spinal dorsal horn pain-transmission neurons."}
{"id": "PMID:216967", "title": "Corynebacterium parvum as an adjuvant for Trypanosoma cruzi epimastigote vaccines: a comparison with saponin and Bordetella pertussis.", "content": "The effect was compared in CBA mice of adding Corynebacterium parvum, saponin, and Bordetella pertussis to living or killed Trypanosoma cruzi (Y strain) epimastigote vaccines on the induction of protective immunity against subcutaneous (s.c.) challenge with blood trypomastigotes. The addition of C. parvum to a low dose of T. cruzi vaccine, which alone was non-protective, generated a greater degree of protection than did saponin or B. pertussis. C. parvum alone increased resistance to infection to a variable and usually weak extent. The addition of C. parvum to larger doses of T. cruzi vaccine, which were themselves sufficient to elicit some degree of protection, improved resistance when the challenge was given 1 or 12 weeks after immunization, but lowered it at 3 weeks. It is concluded that the comparative efficacy of adjuvants for T. cruzi vaccines needs to be assessed on 3 parameters: (1) the dose of antigen, (2) the dose of adjuvant and (3) the time interval between immunization and challenge.", "contents": "Corynebacterium parvum as an adjuvant for Trypanosoma cruzi epimastigote vaccines: a comparison with saponin and Bordetella pertussis. The effect was compared in CBA mice of adding Corynebacterium parvum, saponin, and Bordetella pertussis to living or killed Trypanosoma cruzi (Y strain) epimastigote vaccines on the induction of protective immunity against subcutaneous (s.c.) challenge with blood trypomastigotes. The addition of C. parvum to a low dose of T. cruzi vaccine, which alone was non-protective, generated a greater degree of protection than did saponin or B. pertussis. C. parvum alone increased resistance to infection to a variable and usually weak extent. The addition of C. parvum to larger doses of T. cruzi vaccine, which were themselves sufficient to elicit some degree of protection, improved resistance when the challenge was given 1 or 12 weeks after immunization, but lowered it at 3 weeks. It is concluded that the comparative efficacy of adjuvants for T. cruzi vaccines needs to be assessed on 3 parameters: (1) the dose of antigen, (2) the dose of adjuvant and (3) the time interval between immunization and challenge."}
{"id": "PMID:216969", "title": "Suppression of malignancy in mouse-man hybrid cells.", "content": "Somatic cell hybrids were prepared by fusing malignant mouse melanoma cells with diploid human lymphocytes and fibroblasts in the presence of inactivated Sendai virus. Clones of hybrid cells differed from one another with respect to the number of chromosomes. In particular, human chromosomes were preferentially lost and mouse chromosomes retained. Hybrid clones containing a range of human chromosomes were selected and assayed for tumorigenicity in nude mice, and the presence or absence of specific human chromosomes was correlated with malignancy. Both human lymphocytes and human fibroblasts suppressed the malignancy of mouse melanoma cells. In most cases, suppression of malignancy was complete; in a few cases, tumours developed but the tumorigenicity of these hybrids was considerably less than that of the parent melanoma cells. Chromosome analyses failed to localize the suppressive effect to a specific chromosome.", "contents": "Suppression of malignancy in mouse-man hybrid cells. Somatic cell hybrids were prepared by fusing malignant mouse melanoma cells with diploid human lymphocytes and fibroblasts in the presence of inactivated Sendai virus. Clones of hybrid cells differed from one another with respect to the number of chromosomes. In particular, human chromosomes were preferentially lost and mouse chromosomes retained. Hybrid clones containing a range of human chromosomes were selected and assayed for tumorigenicity in nude mice, and the presence or absence of specific human chromosomes was correlated with malignancy. Both human lymphocytes and human fibroblasts suppressed the malignancy of mouse melanoma cells. In most cases, suppression of malignancy was complete; in a few cases, tumours developed but the tumorigenicity of these hybrids was considerably less than that of the parent melanoma cells. Chromosome analyses failed to localize the suppressive effect to a specific chromosome."}
{"id": "PMID:216970", "title": "Noncondylomatous wart virus infection of the postmenopausal cervix.", "content": "Noncondylomatous papilloma virus infection of the cervix is much more common than formerly realized. The majority of patients are young, but two cases are reported here in postmenopausal women.", "contents": "Noncondylomatous wart virus infection of the postmenopausal cervix. Noncondylomatous papilloma virus infection of the cervix is much more common than formerly realized. The majority of patients are young, but two cases are reported here in postmenopausal women."}
{"id": "PMID:216974", "title": "REM sleep deprivation and pain thresholds in rats.", "content": "The relationship between REM sleep deprivation and pain threshold was measured using 36 Sprague-Dawley female rats. Relative to that of the controls, a significant lowering of threshold to painful electrical stimulation was observed during each of the post-treatment tests, i.e., immediate, and after 3- and 24-hr. recovery periods, for the animals which had been REM deprived.", "contents": "REM sleep deprivation and pain thresholds in rats. The relationship between REM sleep deprivation and pain threshold was measured using 36 Sprague-Dawley female rats. Relative to that of the controls, a significant lowering of threshold to painful electrical stimulation was observed during each of the post-treatment tests, i.e., immediate, and after 3- and 24-hr. recovery periods, for the animals which had been REM deprived."}
{"id": "PMID:216975", "title": "Lack of alpha-adrenergic component in the chronotrophic action of serotonin on isolated atrium of hamster.", "content": "Effects of serotonin on alpha-adrenergic receptors of isolated hamsters' atria preparation were investigated. The positive chronotropic effect of serotonin on isolated atria of the hamster is not related with postsynaptic alpha-adrenergic receptors.", "contents": "Lack of alpha-adrenergic component in the chronotrophic action of serotonin on isolated atrium of hamster. Effects of serotonin on alpha-adrenergic receptors of isolated hamsters' atria preparation were investigated. The positive chronotropic effect of serotonin on isolated atria of the hamster is not related with postsynaptic alpha-adrenergic receptors."}
{"id": "PMID:216976", "title": "Effect of exogenous cAMP in the rabbit right auricle.", "content": "Isotonic solution of cAMP-Na was applied into spontaneously beating auricular fibres by a cut-end method. Cyclic AMP enhanced the spontaneous rate (mean 48%) and increased the contractile tension (mean 297%). These results provided direct evidence that cAMP is involved in the spontaneous activity and contraction in the heart muscle.", "contents": "Effect of exogenous cAMP in the rabbit right auricle. Isotonic solution of cAMP-Na was applied into spontaneously beating auricular fibres by a cut-end method. Cyclic AMP enhanced the spontaneous rate (mean 48%) and increased the contractile tension (mean 297%). These results provided direct evidence that cAMP is involved in the spontaneous activity and contraction in the heart muscle."}
{"id": "PMID:216980", "title": "Atopic dermatitis: clinical and immunologic aspects and treatment.", "content": "Atopic dermatitis is a chronic disease marked by exacerbations and remissions. It begins in early infancy and may persist into late adulthood. Flares of dermatitis may be precipitated by emotional stess, extremes or sudden changes in humidity or temperature, and other factors. Treatment consists primarily of the use of mild topical agents to reduce inflammation and pruritus. Long-term systemic therapy with corticosteroid is not recommended. Topical preparations containing agents that increase the local levels of cyclic adenosine monophosphate (eg, caffeine) may be useful.", "contents": "Atopic dermatitis: clinical and immunologic aspects and treatment. Atopic dermatitis is a chronic disease marked by exacerbations and remissions. It begins in early infancy and may persist into late adulthood. Flares of dermatitis may be precipitated by emotional stess, extremes or sudden changes in humidity or temperature, and other factors. Treatment consists primarily of the use of mild topical agents to reduce inflammation and pruritus. Long-term systemic therapy with corticosteroid is not recommended. Topical preparations containing agents that increase the local levels of cyclic adenosine monophosphate (eg, caffeine) may be useful."}
{"id": "PMID:216977", "title": "The study of the influence of DDT on the antirachitic activity of vitamin D in rats.", "content": "Rachitic Wistar strain rats were administered with a therapeutic dose of vitamin D3 or vitamin D3 with DDT or cod-liver oil containing the same and tenfold larger amount of DDT. No alterations in the activity of vitamin D were found.", "contents": "The study of the influence of DDT on the antirachitic activity of vitamin D in rats. Rachitic Wistar strain rats were administered with a therapeutic dose of vitamin D3 or vitamin D3 with DDT or cod-liver oil containing the same and tenfold larger amount of DDT. No alterations in the activity of vitamin D were found."}
{"id": "PMID:216978", "title": "The effect of drugs stimulating central dopaminergic system on transformation of exogenous adenine into c-AMP.", "content": "We tested the effect of dopamine (DA), apomorphine (APM), amantadine (AMD), dimethylaminoadamantane (DMAD) or haloperidol (HP) on the in vitro formation of c-AMP from ATP labelled intracellularly with exogenous 14C-adenine or from endogenous ATP in the slices of rat striatum. DA stimulated the synthesis of c-AMP from endogenous and 14C-adenine labelled ATP. Nonspecific stimulants of the dopaminergic system, APM, AMD and DMAD, stimulated the c-AMP synthesis much weaker than DA did. After application of APM, ADM or DMAD, the utilization of ATP formed from 14C/U/adenine for synthesis of c-AMP was lower than after DA. The effects of combined treatment with DA together with APM, AMD or DMAD was additive. HP, 1 X 10(-3) M did not change the amount of radioactive and total c-AMP, but inhibited the stimulatory action of DA and, to a lesser degree, of APM, AMD and DMAD. The synthesis of c-AMP from endogenous ATP stimulated with APM, AMD and DMAD in striate body slices was inhibited by HP more strongly than the synthesis of c-AMP from ATP labelled with exogenous 14C-adenine. The results indicate that ATP synthesized from intracellular adenyl nucleotides is more effectively utilized for the synthesis of c-AMP stimulated by APM, AMD or DMAD in striate body slices, than ATP labelled with 14C-adenine.", "contents": "The effect of drugs stimulating central dopaminergic system on transformation of exogenous adenine into c-AMP. We tested the effect of dopamine (DA), apomorphine (APM), amantadine (AMD), dimethylaminoadamantane (DMAD) or haloperidol (HP) on the in vitro formation of c-AMP from ATP labelled intracellularly with exogenous 14C-adenine or from endogenous ATP in the slices of rat striatum. DA stimulated the synthesis of c-AMP from endogenous and 14C-adenine labelled ATP. Nonspecific stimulants of the dopaminergic system, APM, AMD and DMAD, stimulated the c-AMP synthesis much weaker than DA did. After application of APM, ADM or DMAD, the utilization of ATP formed from 14C/U/adenine for synthesis of c-AMP was lower than after DA. The effects of combined treatment with DA together with APM, AMD or DMAD was additive. HP, 1 X 10(-3) M did not change the amount of radioactive and total c-AMP, but inhibited the stimulatory action of DA and, to a lesser degree, of APM, AMD and DMAD. The synthesis of c-AMP from endogenous ATP stimulated with APM, AMD and DMAD in striate body slices was inhibited by HP more strongly than the synthesis of c-AMP from ATP labelled with exogenous 14C-adenine. The results indicate that ATP synthesized from intracellular adenyl nucleotides is more effectively utilized for the synthesis of c-AMP stimulated by APM, AMD or DMAD in striate body slices, than ATP labelled with 14C-adenine."}
{"id": "PMID:216982", "title": "Biochemical studies on endometrium from postmenopausal women receiving hormone replacement therapy.", "content": "Nuclear oestrogen-receptor and soluble progesterone-receptor have been measured in postmenopausal endometria from women receiving either Premarin or Premarin plus norethisterone. Oestradiol dehydrogenase has been measured in some samples. It is concluded that the doses of Premarin currently in use have a potent oestrogenic effect on the endometrium. Norethisterone does not affect the amount of oestrogen entering the nucleus but it may temporarily suppress the biological activity of the oestrogen.", "contents": "Biochemical studies on endometrium from postmenopausal women receiving hormone replacement therapy. Nuclear oestrogen-receptor and soluble progesterone-receptor have been measured in postmenopausal endometria from women receiving either Premarin or Premarin plus norethisterone. Oestradiol dehydrogenase has been measured in some samples. It is concluded that the doses of Premarin currently in use have a potent oestrogenic effect on the endometrium. Norethisterone does not affect the amount of oestrogen entering the nucleus but it may temporarily suppress the biological activity of the oestrogen."}
{"id": "PMID:216979", "title": "Central action of narcotic analgesics. Part III. The role of endogenous noradrenaline in hyperactivity induced by morphine or fentanyl in mice.", "content": "Hyperactivity produced in mice with morphine or fentanyl, and methylamphetamine was antagonized by naloxone. The depression of locomotor activity induced by codeine was practically unchanged by the opiate antagonist. L-DOPA did not restore the stimulatory action of morphine and fentanyl in reserpinized mice. The hyperactivity produced by morphine and fentanyl was abolished in mice treated with alpha-methyl-p-tyrosine, but this was restored by L-DOPA administration. Agents inhibiting the central noradrenaline receptors, phentolamine, phenoxybenzamine, and aceperone, prevented or even reversed the locomotor stimulatory action of morphine and fentanyl. Pimozide did not affect the increase of locomotor activity produced by morphine, but depressed that induced by fentanyl. Haloperidol, used in a dose which did not affect the locomotor activity of mice, completely blocked or even reversed the stimulatory action of morphine and fentanyl, and potentiated the depression of locomotor activity produced by pentazocine and codeine. Diethyldithiocarbamate significantly depressed, but did not inhibit completely the stimulatory action of morphine and fetanyl. The stimulatory action of methylamphetamine was also significantly depressed. It seems that the stimulatory effect of morphine and fentanyl depends on the release of endogenous noradrenaline.", "contents": "Central action of narcotic analgesics. Part III. The role of endogenous noradrenaline in hyperactivity induced by morphine or fentanyl in mice. Hyperactivity produced in mice with morphine or fentanyl, and methylamphetamine was antagonized by naloxone. The depression of locomotor activity induced by codeine was practically unchanged by the opiate antagonist. L-DOPA did not restore the stimulatory action of morphine and fentanyl in reserpinized mice. The hyperactivity produced by morphine and fentanyl was abolished in mice treated with alpha-methyl-p-tyrosine, but this was restored by L-DOPA administration. Agents inhibiting the central noradrenaline receptors, phentolamine, phenoxybenzamine, and aceperone, prevented or even reversed the locomotor stimulatory action of morphine and fentanyl. Pimozide did not affect the increase of locomotor activity produced by morphine, but depressed that induced by fentanyl. Haloperidol, used in a dose which did not affect the locomotor activity of mice, completely blocked or even reversed the stimulatory action of morphine and fentanyl, and potentiated the depression of locomotor activity produced by pentazocine and codeine. Diethyldithiocarbamate significantly depressed, but did not inhibit completely the stimulatory action of morphine and fetanyl. The stimulatory action of methylamphetamine was also significantly depressed. It seems that the stimulatory effect of morphine and fentanyl depends on the release of endogenous noradrenaline."}
{"id": "PMID:216984", "title": "[Daily variations in the secretion of several hormones in obesity].", "content": "The 24-hour variations in the corticotropine, cortizol, thyrotropin, thyroxin, renin, aldosterone, and somatotropin secretion were studied in patients with obesity with the excess of body weight of 51--133% (84.7 + 7.8%) and in healthy persons of normal weight. Obesity proved to be accompanied by marked disturbances of the 24-hour variations of corticotropine, cortizol, thyrotropin, thyroxin, renin, and aldosterone. Unequally marked shifts in 24-hour variations in the secretion of various hormones indicated different changes in the corresponding structures of the hypothalamus during the obesity development. Changes in 24-hour variations in corticotropine and cortizol secretion were in the same direction in alimentary-constitutional and hypothalamic obesity.", "contents": "[Daily variations in the secretion of several hormones in obesity]. The 24-hour variations in the corticotropine, cortizol, thyrotropin, thyroxin, renin, aldosterone, and somatotropin secretion were studied in patients with obesity with the excess of body weight of 51--133% (84.7 + 7.8%) and in healthy persons of normal weight. Obesity proved to be accompanied by marked disturbances of the 24-hour variations of corticotropine, cortizol, thyrotropin, thyroxin, renin, and aldosterone. Unequally marked shifts in 24-hour variations in the secretion of various hormones indicated different changes in the corresponding structures of the hypothalamus during the obesity development. Changes in 24-hour variations in corticotropine and cortizol secretion were in the same direction in alimentary-constitutional and hypothalamic obesity."}
{"id": "PMID:216985", "title": "[Lipid-cellular (lipoid-cellular) tumors of the ovaries].", "content": "In accordance with in International Histological Classification of the ovaries lipidocellular (lipoidocellular) tumours are referred to a separate group. Analysis of literature data and the author's observations demonstrated that neoplasms differing by histogenesis of newgrowth formation were placed in this group. Evidence in favour of revision of this point of the classification is presented, and suitable recommendations are given.", "contents": "[Lipid-cellular (lipoid-cellular) tumors of the ovaries]. In accordance with in International Histological Classification of the ovaries lipidocellular (lipoidocellular) tumours are referred to a separate group. Analysis of literature data and the author's observations demonstrated that neoplasms differing by histogenesis of newgrowth formation were placed in this group. Evidence in favour of revision of this point of the classification is presented, and suitable recommendations are given."}
{"id": "PMID:216989", "title": "Evaluation of plasma neurotoxin concentration in uraemic polyneuropathic patients.", "content": "Purification of b4-2 sub-peak obtained on DEAE Sephadex A25 chromatography gave us the possibility of quantifying the plasma concentration of the neurotoxin present in uraemic patients with active polyneuropathy. From the purified neurotoxin isolated by kieselguhr and cellulose chromatography we calibrated analytic columns for b4-2 analysis. Plasma concentration, measured in 6 uraemic neuropathic patients, is between 13 and 19 mg/litre. In 52 uraemic patients without neuropathy, the plasma concentration is between 3 and 9 mg/litre. In 20 healthy subjects the plasma concentration is less than 1 mg/litre. The weekly neurotoxin removal in uraemic patients without neuropathy, treated  by a five hours RP6 session 3 times a week, is of the same order of magnitude as the weekly urinary excretion in healthy subjects. Preliminary results of a tentative identification of this purified product indicate that it is not a polypeptide but an acid-polyol with carbohydrate structure.", "contents": "Evaluation of plasma neurotoxin concentration in uraemic polyneuropathic patients. Purification of b4-2 sub-peak obtained on DEAE Sephadex A25 chromatography gave us the possibility of quantifying the plasma concentration of the neurotoxin present in uraemic patients with active polyneuropathy. From the purified neurotoxin isolated by kieselguhr and cellulose chromatography we calibrated analytic columns for b4-2 analysis. Plasma concentration, measured in 6 uraemic neuropathic patients, is between 13 and 19 mg/litre. In 52 uraemic patients without neuropathy, the plasma concentration is between 3 and 9 mg/litre. In 20 healthy subjects the plasma concentration is less than 1 mg/litre. The weekly neurotoxin removal in uraemic patients without neuropathy, treated  by a five hours RP6 session 3 times a week, is of the same order of magnitude as the weekly urinary excretion in healthy subjects. Preliminary results of a tentative identification of this purified product indicate that it is not a polypeptide but an acid-polyol with carbohydrate structure."}
{"id": "PMID:216990", "title": "Human polyoma virus (HPV)--a significant pathogen in renal transplantation.", "content": "Routine cytological screening of Papanicolaou-stained smears of the urinary sediment from 57 renal allografts in 51 patients has resulted in the detection of seven cases of Human Polyoma Virus (HPV) BK infection--14% of the total number. Infection was confirmed by virus isolation and electron microscopy (EM). The cytological, histological and ultra-structural data are described and related to the clinical progress of the patient. Four out of the seven cases are discussed in more detail as histological material was available; in three of these, there was evidence of stenosis of the transplant ureter with virus infected cells in the ureteric epithelium and in one case also in the renal tubules. Administration of high dose steroids may provoke active infection with HPV in ureteric epithelium damaged by ischaemia and inflammation. The similarity between the clinical features of an HPV infection and a rejection episode make it imperative to confirm the diagnosis quickly and accurately. Cytological examination of the urinary deposit by light microscopy is a simple, inexpensive procedure which provides positive diagnosis of the typical virus inclusions within an hour of receiving the urine specimen in the laboratory. This can be confirmed by removing single cells from the original cytological slide preparation and processing them for EM using a technique described by Coleman et al [1].", "contents": "Human polyoma virus (HPV)--a significant pathogen in renal transplantation. Routine cytological screening of Papanicolaou-stained smears of the urinary sediment from 57 renal allografts in 51 patients has resulted in the detection of seven cases of Human Polyoma Virus (HPV) BK infection--14% of the total number. Infection was confirmed by virus isolation and electron microscopy (EM). The cytological, histological and ultra-structural data are described and related to the clinical progress of the patient. Four out of the seven cases are discussed in more detail as histological material was available; in three of these, there was evidence of stenosis of the transplant ureter with virus infected cells in the ureteric epithelium and in one case also in the renal tubules. Administration of high dose steroids may provoke active infection with HPV in ureteric epithelium damaged by ischaemia and inflammation. The similarity between the clinical features of an HPV infection and a rejection episode make it imperative to confirm the diagnosis quickly and accurately. Cytological examination of the urinary deposit by light microscopy is a simple, inexpensive procedure which provides positive diagnosis of the typical virus inclusions within an hour of receiving the urine specimen in the laboratory. This can be confirmed by removing single cells from the original cytological slide preparation and processing them for EM using a technique described by Coleman et al [1]."}
{"id": "PMID:216986", "title": "[Indirect lymphography of the thyroid gland. 2].", "content": "Indirect lymphography of the thyroid gland was performed in 144 patients. A conclusion was drawn that the use of superfluid oil contrast preparations of lipidol, miodyl type etc. in indirect lymphography of the thyroid gland will permit to obtain the exhaustive information on the state of the endocrine organ and regional lymph nodes. Lymphography with the aid of oil contrast preparation iodolipol diluted with ether and heated to the body temperature is less informative; water-soluble contrast agents were less effective. All the test contrast agents proved to be ineffective for detection of changes in the lymph nodes. Use of iodolipol for lymphography of the thyroid gland without preliminary mixture with ether is not recommended.", "contents": "[Indirect lymphography of the thyroid gland. 2]. Indirect lymphography of the thyroid gland was performed in 144 patients. A conclusion was drawn that the use of superfluid oil contrast preparations of lipidol, miodyl type etc. in indirect lymphography of the thyroid gland will permit to obtain the exhaustive information on the state of the endocrine organ and regional lymph nodes. Lymphography with the aid of oil contrast preparation iodolipol diluted with ether and heated to the body temperature is less informative; water-soluble contrast agents were less effective. All the test contrast agents proved to be ineffective for detection of changes in the lymph nodes. Use of iodolipol for lymphography of the thyroid gland without preliminary mixture with ether is not recommended."}
{"id": "PMID:216993", "title": "Erythro-9-(2-hydroxy-3-nonyl)adenine as a specific inhibitor of herpes simplex virus replication in the presence and absence of adenosine analogues.", "content": "Erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA; erythro-9-[3-(hydroxynonyl)]adenine), a reversible inhibitor of adenosine deaminase, significantly inhibits replication of herpes simplex virus (HSV), whereas the more active inhibitor of the deaminase, 2'-deoxycoformycin, does not. At 10 micron EHNA, which does not affect viability, growth, or DNA synthesis of uninfected HeLa cells, production of HSV and HSV-specific DNA is inhibited 75-90% and 60%, respectively. HSV multiplies normally in cells pretreated with EHNA and washed to remove this inhibitor. EHNA (10 micron) also markedly potentiates the toxicity of adenine arabinonucleoside and of cordycepin (3'-deoxyadenosine) against HeLa cells and against the production of HSV in those cells. Cordycepin alone (10 micron) does not inhibit HSV replication whereas in combination with 10 micron EHNA there is a greater than 99% inhibition of virus production. Under these conditions, RNA synthesis is inhibited by more than 80% whereas protein and DNA synthesis are inhibited to a lesser extent; in this system, virtually all of the DNA synthesis in infected cells is that of host DNA. Thus, EHNA appears to affect the synthesis of HSV DNA specifically in two different ways, depending on whether it is used alone or in the presence of cordycepin.", "contents": "Erythro-9-(2-hydroxy-3-nonyl)adenine as a specific inhibitor of herpes simplex virus replication in the presence and absence of adenosine analogues. Erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA; erythro-9-[3-(hydroxynonyl)]adenine), a reversible inhibitor of adenosine deaminase, significantly inhibits replication of herpes simplex virus (HSV), whereas the more active inhibitor of the deaminase, 2'-deoxycoformycin, does not. At 10 micron EHNA, which does not affect viability, growth, or DNA synthesis of uninfected HeLa cells, production of HSV and HSV-specific DNA is inhibited 75-90% and 60%, respectively. HSV multiplies normally in cells pretreated with EHNA and washed to remove this inhibitor. EHNA (10 micron) also markedly potentiates the toxicity of adenine arabinonucleoside and of cordycepin (3'-deoxyadenosine) against HeLa cells and against the production of HSV in those cells. Cordycepin alone (10 micron) does not inhibit HSV replication whereas in combination with 10 micron EHNA there is a greater than 99% inhibition of virus production. Under these conditions, RNA synthesis is inhibited by more than 80% whereas protein and DNA synthesis are inhibited to a lesser extent; in this system, virtually all of the DNA synthesis in infected cells is that of host DNA. Thus, EHNA appears to affect the synthesis of HSV DNA specifically in two different ways, depending on whether it is used alone or in the presence of cordycepin."}
{"id": "PMID:216994", "title": "Exposure of DNA bases induced by the interaction of DNA and calf thymus DNA helix-destabilizing protein.", "content": "The reaction of chloroacetaldehyde with adenine bases in DNA to give a fluorescent product was used to study the availability to intermolecular reaction of positions 1 and 6 of adenine in DNA complexes with calf thymus DNA helix-destabilizing protein. No inhibition of this reaction was observed when heat-denatured DNA was complexed with the protein at a protein/DNA weight ratio of 10:1, compared to free DNA. On the contrary, the same reaction was inhibited markedly for denatured DNA in the presence of calf thymus histone HI at protein/DNA weight ratio of 2:1. Furthermore, the exchange rate for hydrogens of amino and imide groups of DNA bases in DNA strands with deuterium in the solvent was totally unaffected upon complexing of DNA with the DNA helix-destabilizing protein as examined by stopped-flow ultraviolet spectroscopy. These results indicate that the DNA helix-destabilizing protein forms a complex with single-stranded DNA, leaving DNA bases uncovered by the protein. The fluorescence intensity of DNA pretreated with chloroacetaldehyde was amplified by nearly 3-fold upon addition of the DNA helix-destabilizing protein. The possibility of \"unstacking\" of DNA bases induced by the protein is discussed.", "contents": "Exposure of DNA bases induced by the interaction of DNA and calf thymus DNA helix-destabilizing protein. The reaction of chloroacetaldehyde with adenine bases in DNA to give a fluorescent product was used to study the availability to intermolecular reaction of positions 1 and 6 of adenine in DNA complexes with calf thymus DNA helix-destabilizing protein. No inhibition of this reaction was observed when heat-denatured DNA was complexed with the protein at a protein/DNA weight ratio of 10:1, compared to free DNA. On the contrary, the same reaction was inhibited markedly for denatured DNA in the presence of calf thymus histone HI at protein/DNA weight ratio of 2:1. Furthermore, the exchange rate for hydrogens of amino and imide groups of DNA bases in DNA strands with deuterium in the solvent was totally unaffected upon complexing of DNA with the DNA helix-destabilizing protein as examined by stopped-flow ultraviolet spectroscopy. These results indicate that the DNA helix-destabilizing protein forms a complex with single-stranded DNA, leaving DNA bases uncovered by the protein. The fluorescence intensity of DNA pretreated with chloroacetaldehyde was amplified by nearly 3-fold upon addition of the DNA helix-destabilizing protein. The possibility of \"unstacking\" of DNA bases induced by the protein is discussed."}
{"id": "PMID:216995", "title": "Chemical determination of the m1 Moloney sarcoma virus pP60gag gene order: evidence for unique peptides in the carboxy terminus of the polyprotein.", "content": "The gene order of the ml Moloney sarcoma virus (mlMSV) specific pP60gag (P60) was determined by direct chemical analysis of the polyprotein. P60 was cleaved with cyanogen bromide (CNBr) into eight partial and complete fragments ranging in mass from 10,000 daltons to 58,000 daltons. Peptide maps of these fragments were compared to maps of p15, p12, and three CNBr fragments of p30. The polarity of p15 and p12 in a CNBr fragment of P60 was determined by carboxypeptidase A digestion; likewise the CNBr fragments of p30 were ordered by aminopeptidase digestion. The linear arrangement of P60 CNBr fragments gave the gene order of NH2-p15-p12-p30-COOH. The m3 isolate of MSV expresses a P70 gag polyprotein. Peptide maps of 48,000-dalton CNBr fragments of m3 P70 and ml P60 were similar and suggested that both polyproteins were similar through the NH2-terminal two-thirds of p30. However, the presence of peptides unique to the 10,500-dalton COOH-terminal fragment of m1MSV p30 and not present in the p30 of either m3MSV or Moloney leukemia virus suggested that the gag gene deletion in the m1 isolate begins in the p30 reading frame.", "contents": "Chemical determination of the m1 Moloney sarcoma virus pP60gag gene order: evidence for unique peptides in the carboxy terminus of the polyprotein. The gene order of the ml Moloney sarcoma virus (mlMSV) specific pP60gag (P60) was determined by direct chemical analysis of the polyprotein. P60 was cleaved with cyanogen bromide (CNBr) into eight partial and complete fragments ranging in mass from 10,000 daltons to 58,000 daltons. Peptide maps of these fragments were compared to maps of p15, p12, and three CNBr fragments of p30. The polarity of p15 and p12 in a CNBr fragment of P60 was determined by carboxypeptidase A digestion; likewise the CNBr fragments of p30 were ordered by aminopeptidase digestion. The linear arrangement of P60 CNBr fragments gave the gene order of NH2-p15-p12-p30-COOH. The m3 isolate of MSV expresses a P70 gag polyprotein. Peptide maps of 48,000-dalton CNBr fragments of m3 P70 and ml P60 were similar and suggested that both polyproteins were similar through the NH2-terminal two-thirds of p30. However, the presence of peptides unique to the 10,500-dalton COOH-terminal fragment of m1MSV p30 and not present in the p30 of either m3MSV or Moloney leukemia virus suggested that the gag gene deletion in the m1 isolate begins in the p30 reading frame."}
{"id": "PMID:216996", "title": "Sequence of a RNA templated by the 3'-OH RNA terminus of defective interfering particles of vesicular stomatitis virus.", "content": "We have sequenced the endogenous RNA polymerase product produced by disrupted purified virions of vesicular stomatitis virus defective interfering particles by using the newer one-dimensional rapid gel sequencing techniques and confirming this with a modified two-dimensional gel vectoring technique. The sequence of this 46-nucleotide RNA is: 5'(pp)pACGAAGACCACAAAACCA-GAUAAAAAAUAAAAACCACAAGAGGG(U)COH3'. We infer that this sequence is identical to the sequence at the 5' end of infectious vesicular stomatitis virus RNA and is complementary to the sequence of the 3'-OH terminus of this defective interfering particle genome RNA.", "contents": "Sequence of a RNA templated by the 3'-OH RNA terminus of defective interfering particles of vesicular stomatitis virus. We have sequenced the endogenous RNA polymerase product produced by disrupted purified virions of vesicular stomatitis virus defective interfering particles by using the newer one-dimensional rapid gel sequencing techniques and confirming this with a modified two-dimensional gel vectoring technique. The sequence of this 46-nucleotide RNA is: 5'(pp)pACGAAGACCACAAAACCA-GAUAAAAAAUAAAAACCACAAGAGGG(U)COH3'. We infer that this sequence is identical to the sequence at the 5' end of infectious vesicular stomatitis virus RNA and is complementary to the sequence of the 3'-OH terminus of this defective interfering particle genome RNA."}
{"id": "PMID:216997", "title": "Biosynthesis of beta-endorphin from beta-lipotropin and a larger molecular weight precursor in rat pars intermedia.", "content": "When isolated rat pars intermedia cells were incubated for 10 min with radioactive amino acids, one major labeled protein with a molecular weight of 30,000 +/- 1500 was extracted. This protein was shown to contain in its sequence the antigenic determinants for corticotropin and beta-melanotropin by immunoprecipitation. When the radioactivity incorporated into this large molecular weight protein during the first 10 min was chased by a further incubation in presence of an excess of unlabeled amino acid, the initial protein was degraded into several smaller peptides including beta-endorphin and beta-lipotropin. Another 18,000-dalton peptide was also observed and was tentatively identified as a large molecular form of corticotropin. From the kinetics of the maturation of the initial precursor, it is concluded that the initial cleavage of the 30,000-dalton peptide gives rise to beta-lipotropin and the 18,000-dalton form of corticotropin. beta-Lipotropin is subsequently cleaved to form beta-endorphin.", "contents": "Biosynthesis of beta-endorphin from beta-lipotropin and a larger molecular weight precursor in rat pars intermedia. When isolated rat pars intermedia cells were incubated for 10 min with radioactive amino acids, one major labeled protein with a molecular weight of 30,000 +/- 1500 was extracted. This protein was shown to contain in its sequence the antigenic determinants for corticotropin and beta-melanotropin by immunoprecipitation. When the radioactivity incorporated into this large molecular weight protein during the first 10 min was chased by a further incubation in presence of an excess of unlabeled amino acid, the initial protein was degraded into several smaller peptides including beta-endorphin and beta-lipotropin. Another 18,000-dalton peptide was also observed and was tentatively identified as a large molecular form of corticotropin. From the kinetics of the maturation of the initial precursor, it is concluded that the initial cleavage of the 30,000-dalton peptide gives rise to beta-lipotropin and the 18,000-dalton form of corticotropin. beta-Lipotropin is subsequently cleaved to form beta-endorphin."}
{"id": "PMID:216998", "title": "Polyoma virus giant RNAs contain tandem repeats of the nucleotide sequence of the entire viral genome.", "content": "The bulk of late virus-specific RNA synthesized in polyoma virus-infected mouse cells is larger than a single strand of poloma DNA. The arrangement of viral nucleotide sequences in these giant polyoma RNAs was studied by electron microscopy of hybrids between purified high molecular weight viral RNA and the HindII-1 fragment of polyoma DNA, which contains 91% of the viral genome. Hybrid molecules containing a short single-stranded gap (corresponding to the 9% of viral sequences not present in HindII-1), flanked by double-stranded regions, were photographed and measured. The majority of hybrid molecules contained no single-stranded loops or branches, showing that all viral sequences are transcribed contiguously and that no nonviral sequences are present in the RNA. Hybrid molecules, containing RNA up to 3.5 times the genome length, had a repeating structure of single-stranded gaps 8% of genome length interspersed with double-stranded regions 89% of genome length, showing that giant polyoma RNAs contain tandem repeats of the nucleotide sequence of the entire viral DNA. A small proportion of hybrid molecules contained single-stranded branches or deletion loops in characteristic positions, indicating that RNA \"splicing\" may occur on high molecular weight nuclear polyoma RNA.", "contents": "Polyoma virus giant RNAs contain tandem repeats of the nucleotide sequence of the entire viral genome. The bulk of late virus-specific RNA synthesized in polyoma virus-infected mouse cells is larger than a single strand of poloma DNA. The arrangement of viral nucleotide sequences in these giant polyoma RNAs was studied by electron microscopy of hybrids between purified high molecular weight viral RNA and the HindII-1 fragment of polyoma DNA, which contains 91% of the viral genome. Hybrid molecules containing a short single-stranded gap (corresponding to the 9% of viral sequences not present in HindII-1), flanked by double-stranded regions, were photographed and measured. The majority of hybrid molecules contained no single-stranded loops or branches, showing that all viral sequences are transcribed contiguously and that no nonviral sequences are present in the RNA. Hybrid molecules, containing RNA up to 3.5 times the genome length, had a repeating structure of single-stranded gaps 8% of genome length interspersed with double-stranded regions 89% of genome length, showing that giant polyoma RNAs contain tandem repeats of the nucleotide sequence of the entire viral DNA. A small proportion of hybrid molecules contained single-stranded branches or deletion loops in characteristic positions, indicating that RNA \"splicing\" may occur on high molecular weight nuclear polyoma RNA."}
{"id": "PMID:216999", "title": "Gonadal luteinizing hormone receptors and adenylate cyclase: transfer of functional ovarian luteinizing hormone receptors to adrenal fasciculata cells.", "content": "Luteinized rat ovaries contain a high concentration of particulate luteinizing hormone (lutropin, LH) receptors and a small quantity of lipid-associated receptors that float in the 360,000 X g supernatant fraction of ovarian homogenates. During fractionation of Lubrol-solubilized LH receptors and adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] from the ovary and testis, LH receptors and adenylate cyclase were coincident on gel filtration, but could be resolved during ion-exchange chromatography of soluble ovarian preparations and were completely separated by lectin-affinity chromatography on Sepharose-concanavalin A. For further analysis of receptor-adenylate cyclase coupling, the lipid-rich fraction of ovarian luteal cells was used to transfer gonadal LH receptors to isolated adrenal fasciculata cells. The lipid vesicles obtained from ovarian homogenates by flotation at 360,000 X g contained 5--10% of the ovarian LH receptors and were devoid of adenylate cyclase activity. During incubation of lipid-associated receptors with dispersed rat fasciculata cells at 16 degrees C, progressive incorporation of LH binding sites into the adrenal cells was observed. When adrenal cells bearing heterotopic LH receptors were incubated with 1 nM human choriogonadotropin, cyclic AMP production was consistently stimulated, with an accompanying increase in corticosterone production. These results indicate that LH receptors exist as separate entities from adenylate cyclase in the gonadal cell membrane and can become functionally coupled to adenylate cyclase to evoke cyclic AMP production and steroidogenesis in the host adrenal cells to which they are transferred.", "contents": "Gonadal luteinizing hormone receptors and adenylate cyclase: transfer of functional ovarian luteinizing hormone receptors to adrenal fasciculata cells. Luteinized rat ovaries contain a high concentration of particulate luteinizing hormone (lutropin, LH) receptors and a small quantity of lipid-associated receptors that float in the 360,000 X g supernatant fraction of ovarian homogenates. During fractionation of Lubrol-solubilized LH receptors and adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] from the ovary and testis, LH receptors and adenylate cyclase were coincident on gel filtration, but could be resolved during ion-exchange chromatography of soluble ovarian preparations and were completely separated by lectin-affinity chromatography on Sepharose-concanavalin A. For further analysis of receptor-adenylate cyclase coupling, the lipid-rich fraction of ovarian luteal cells was used to transfer gonadal LH receptors to isolated adrenal fasciculata cells. The lipid vesicles obtained from ovarian homogenates by flotation at 360,000 X g contained 5--10% of the ovarian LH receptors and were devoid of adenylate cyclase activity. During incubation of lipid-associated receptors with dispersed rat fasciculata cells at 16 degrees C, progressive incorporation of LH binding sites into the adrenal cells was observed. When adrenal cells bearing heterotopic LH receptors were incubated with 1 nM human choriogonadotropin, cyclic AMP production was consistently stimulated, with an accompanying increase in corticosterone production. These results indicate that LH receptors exist as separate entities from adenylate cyclase in the gonadal cell membrane and can become functionally coupled to adenylate cyclase to evoke cyclic AMP production and steroidogenesis in the host adrenal cells to which they are transferred."}
{"id": "PMID:217000", "title": "Enzymatic conversion of 5'-phosphate-terminated RNA to 5'-di- and triphosphate-terminated RNA.", "content": "We have isolated from vaccinia virus cores an enzyme, 5'-phosphate-polyribonucleotide kinase, that in the presence of ATP and Mg2+ catalyzes the conversion of 5'-phosphate and 5'-diphosphate termini of RNA to the 5'-triphosphate species. With the exception of dATP, other nucleoside triphosphates were inactive as phosphate donors; activity with dATP was 10% of that observed with ATP. The purified enzyme did not phosphorylate 5'-hydroxyl- or 5'-monophosphate-terminated polydeoxyribonucleotides, although a variety of 5'- monophosphate-terminated RNA chains were active as phosphate acceptors. By using a coupled system of 5'-phosphate-polyribonucleotide kinase and guanylyltransferase in the presence of ATP, GTP, Mg2+, and S-adenosylmethionine, capping of 5'-P-, 5'-PP-, and 5'-PPP-RNA was demonstrated; in the absence of 5'-phosphate-polyribonucleotide kinase only 5'-PPP-RNA was capped by guanylyltransferase.", "contents": "Enzymatic conversion of 5'-phosphate-terminated RNA to 5'-di- and triphosphate-terminated RNA. We have isolated from vaccinia virus cores an enzyme, 5'-phosphate-polyribonucleotide kinase, that in the presence of ATP and Mg2+ catalyzes the conversion of 5'-phosphate and 5'-diphosphate termini of RNA to the 5'-triphosphate species. With the exception of dATP, other nucleoside triphosphates were inactive as phosphate donors; activity with dATP was 10% of that observed with ATP. The purified enzyme did not phosphorylate 5'-hydroxyl- or 5'-monophosphate-terminated polydeoxyribonucleotides, although a variety of 5'- monophosphate-terminated RNA chains were active as phosphate acceptors. By using a coupled system of 5'-phosphate-polyribonucleotide kinase and guanylyltransferase in the presence of ATP, GTP, Mg2+, and S-adenosylmethionine, capping of 5'-P-, 5'-PP-, and 5'-PPP-RNA was demonstrated; in the absence of 5'-phosphate-polyribonucleotide kinase only 5'-PPP-RNA was capped by guanylyltransferase."}
{"id": "PMID:217001", "title": "Interferoids: in vitro and in vivo conversion of native interferons to lower molecular weight forms.", "content": "Mouse interferons appear as two distinct molecular forms, one migrating at 38,000 daltons in sodium dodecyl sulfate/polyacrylamide gels and one migrating at 22,000 daltons; these interferons comprise about 80% and 20% of total activities, respectively. When such interferon preparations are briefly exposed to acidic periodate buffer, the larger interferon species is apparently converted to the smaller form since the activity at 38,000 daltons is completely eliminated while the activity at 22,000 daltons increases significantly; upon further oxidative cleavage, antiviral activity becomes detectable migrating at 15,000 daltons. Because no native mouse interferon has been reported as such small molecules, this antiviral activity is designated mouse \"interferoid\" to distinguish it from the native, naturally occurring interferon forms. Prolonged acidperiodate treatment fails to quantitatively convert the 22,000-dalton interferon to the 15,000-dalton interferoid since both are inactivated. When L cells are induced to make interferon in the presence of glycosylation inhibitors, either D-glucosamine or 2-deoxy-D-glucose, they produce approximately normal levels of antiviral activity. However, when such preparations are analyzed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis, little activity (<10%) migrates as either the 38,000-dalton or 22,000-dalton native interferons. The interferons and interferoid are antigenically and hydrophobically indistinguishable. These data suggest that induced mouse cells normally synthesize the interferoid as a precursor polypeptide that is either partially or extensively modified by carbohydrate additions to produce, respectively, the 22,000- and 38,000-dalton mouse interferons. Because interferoid is apparently fully biologically active without these moieties, chemical synthesis of such unmodified polypeptides or active fragments from them appears feasible.", "contents": "Interferoids: in vitro and in vivo conversion of native interferons to lower molecular weight forms. Mouse interferons appear as two distinct molecular forms, one migrating at 38,000 daltons in sodium dodecyl sulfate/polyacrylamide gels and one migrating at 22,000 daltons; these interferons comprise about 80% and 20% of total activities, respectively. When such interferon preparations are briefly exposed to acidic periodate buffer, the larger interferon species is apparently converted to the smaller form since the activity at 38,000 daltons is completely eliminated while the activity at 22,000 daltons increases significantly; upon further oxidative cleavage, antiviral activity becomes detectable migrating at 15,000 daltons. Because no native mouse interferon has been reported as such small molecules, this antiviral activity is designated mouse \"interferoid\" to distinguish it from the native, naturally occurring interferon forms. Prolonged acidperiodate treatment fails to quantitatively convert the 22,000-dalton interferon to the 15,000-dalton interferoid since both are inactivated. When L cells are induced to make interferon in the presence of glycosylation inhibitors, either D-glucosamine or 2-deoxy-D-glucose, they produce approximately normal levels of antiviral activity. However, when such preparations are analyzed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis, little activity (<10%) migrates as either the 38,000-dalton or 22,000-dalton native interferons. The interferons and interferoid are antigenically and hydrophobically indistinguishable. These data suggest that induced mouse cells normally synthesize the interferoid as a precursor polypeptide that is either partially or extensively modified by carbohydrate additions to produce, respectively, the 22,000- and 38,000-dalton mouse interferons. Because interferoid is apparently fully biologically active without these moieties, chemical synthesis of such unmodified polypeptides or active fragments from them appears feasible."}
{"id": "PMID:217002", "title": "A polypeptide in eukaryotic initiation factors that crosslinks specifically to the 5'-terminal cap in mRNA.", "content": "Protein synthesis initiation factors prepared from rabbit reticulocyte and mouse ascites ribosomes were tested for the ability to crosslink to the 5' cap of mRNA. Crosslinking of one polypeptide of apparent molecular weight 24,000 was inhibited by the cap analogs, m7GMP and m7GDP, indicating a specific interaction with the cap. Although specific crosslinking of the 24,000 molecular weight polypeptide was found with eukaryotic initiation factor 3 and to a lesser extent with initiation factor 4B, both of these factors contained less than stoichiometric amounts of this polypeptide. The crosslinking method provides a highly sensitive and specific assay for cap-binding proteins and should facilitate their purification for functional studies.", "contents": "A polypeptide in eukaryotic initiation factors that crosslinks specifically to the 5'-terminal cap in mRNA. Protein synthesis initiation factors prepared from rabbit reticulocyte and mouse ascites ribosomes were tested for the ability to crosslink to the 5' cap of mRNA. Crosslinking of one polypeptide of apparent molecular weight 24,000 was inhibited by the cap analogs, m7GMP and m7GDP, indicating a specific interaction with the cap. Although specific crosslinking of the 24,000 molecular weight polypeptide was found with eukaryotic initiation factor 3 and to a lesser extent with initiation factor 4B, both of these factors contained less than stoichiometric amounts of this polypeptide. The crosslinking method provides a highly sensitive and specific assay for cap-binding proteins and should facilitate their purification for functional studies."}
{"id": "PMID:217003", "title": "O4-(5'-uridylyl)tyrosine is the bond between the genome-linked protein and the RNA of poliovirus.", "content": "Virion RNA of poliovirus type 1 has been analyzed for the linkage between genome-protein VPg and the polyribonucleotide chain. Hydrolysis of the linkage with acid or alkali and enzymatic degradation lead to the conclusion that the bond is neither a phosphodiester such as nucleotidyl-(P-O)-serine (or threonine) nor a phosphoramidate such as nucleotidyl-(P-N)-amino acid. VPg-RNA can be iodinated by the Bolton and Hunter reagent [iodinated 3-(4-hydroxyphenyl)propionic acid N-hydroxysuccinimide ester] but not by the chloramine-T or lactoperoxidase procedures, an observation suggesting that VPg does not contain accessible tyrosine. However, VPg can be labeled with [3H]tyrosine in vivo. Hydrolysis of VPg-[32P]pUp with 5.6 M HCl at 110 degrees yielded 32P-labeled O4-(3'-phospho-5'-uridylyl)tyrosine that could be cleaved with micrococcal nuclease to O4-[32P]phosphotyrosine and uridine 3'-[32P]phosphate. These data establish that VPg is linked to the poliovirus genome by a bond between the O4 of tyrosine and the 5'-P atom of the terminal uridylic acid residue. The 5' end of polio genome RNA can now be described as VPg(Tyr-O)-pU-U-A-A-A-A-C-A-G.", "contents": "O4-(5'-uridylyl)tyrosine is the bond between the genome-linked protein and the RNA of poliovirus. Virion RNA of poliovirus type 1 has been analyzed for the linkage between genome-protein VPg and the polyribonucleotide chain. Hydrolysis of the linkage with acid or alkali and enzymatic degradation lead to the conclusion that the bond is neither a phosphodiester such as nucleotidyl-(P-O)-serine (or threonine) nor a phosphoramidate such as nucleotidyl-(P-N)-amino acid. VPg-RNA can be iodinated by the Bolton and Hunter reagent [iodinated 3-(4-hydroxyphenyl)propionic acid N-hydroxysuccinimide ester] but not by the chloramine-T or lactoperoxidase procedures, an observation suggesting that VPg does not contain accessible tyrosine. However, VPg can be labeled with [3H]tyrosine in vivo. Hydrolysis of VPg-[32P]pUp with 5.6 M HCl at 110 degrees yielded 32P-labeled O4-(3'-phospho-5'-uridylyl)tyrosine that could be cleaved with micrococcal nuclease to O4-[32P]phosphotyrosine and uridine 3'-[32P]phosphate. These data establish that VPg is linked to the poliovirus genome by a bond between the O4 of tyrosine and the 5'-P atom of the terminal uridylic acid residue. The 5' end of polio genome RNA can now be described as VPg(Tyr-O)-pU-U-A-A-A-A-C-A-G."}
{"id": "PMID:217004", "title": "DNA supercoiling by Xenopus laevis oocyte extracts: requirement for a nuclear factor.", "content": "A purified system is described for the introduction of negative supercoils into simian virus 40 DNA. The system consists of histones H2A, H2B, H3, and H4, DNA-relaxing enzyme, and a purified factor from Xenopus laevis stage 6 oocyte nuclei. The nuclei are prepared en masse by the technique of F. Scalenghe, M. Buscaglia, C. Steinheil, and M. Crippa [(1978) Chromosoma 60, 299-308]. The supercoiled simian virus 40 DNA prepared by this method is indistinguishable from simian virus 40 supercoiled DNA prepared from infected monkey cells.", "contents": "DNA supercoiling by Xenopus laevis oocyte extracts: requirement for a nuclear factor. A purified system is described for the introduction of negative supercoils into simian virus 40 DNA. The system consists of histones H2A, H2B, H3, and H4, DNA-relaxing enzyme, and a purified factor from Xenopus laevis stage 6 oocyte nuclei. The nuclei are prepared en masse by the technique of F. Scalenghe, M. Buscaglia, C. Steinheil, and M. Crippa [(1978) Chromosoma 60, 299-308]. The supercoiled simian virus 40 DNA prepared by this method is indistinguishable from simian virus 40 supercoiled DNA prepared from infected monkey cells."}
{"id": "PMID:217005", "title": "Electron spin resonance studies on interaction of complement proteins with erythrocyte membranes.", "content": "Sheep erythrocytes have been spin labeled with 5-, 12-, and 16-nitroxystearic acid in order to investigate complement-induced changes in the physical state of the lipid bilayer. Formation of osmotic lesions in the membrane causes an increase in the fluidity of the membrane which overcomes the decrease in membrane fluidity caused by the interaction of the complement proteins. A decrease in membrane fluidity is observed only when complement-lysed membranes are resealed or when complement proteins react with isosmolar ghosts that do not undergo osmotic lysis. The decrease in bulk fluidity of the membrane is first observed when C8 binds to the membranes bearing C5b67 and is enhanced upon the subsequent binding of C9. The decrease in membrane fluidity shown by the electron spin resonance spectra of spin-labeled fatty acids suggests that certain of the complement proteins penetrate the membrane and interact with hydrophobic regions of the lipid bilayer.", "contents": "Electron spin resonance studies on interaction of complement proteins with erythrocyte membranes. Sheep erythrocytes have been spin labeled with 5-, 12-, and 16-nitroxystearic acid in order to investigate complement-induced changes in the physical state of the lipid bilayer. Formation of osmotic lesions in the membrane causes an increase in the fluidity of the membrane which overcomes the decrease in membrane fluidity caused by the interaction of the complement proteins. A decrease in membrane fluidity is observed only when complement-lysed membranes are resealed or when complement proteins react with isosmolar ghosts that do not undergo osmotic lysis. The decrease in bulk fluidity of the membrane is first observed when C8 binds to the membranes bearing C5b67 and is enhanced upon the subsequent binding of C9. The decrease in membrane fluidity shown by the electron spin resonance spectra of spin-labeled fatty acids suggests that certain of the complement proteins penetrate the membrane and interact with hydrophobic regions of the lipid bilayer."}
{"id": "PMID:217006", "title": "Codistribution of pericellular matrix proteins in cultured fibroblasts and loss in transformation: fibronectin and procollagen.", "content": "Antibodies to fibronectin and to distinct types of procollagens and collagens were used in immunofluorescent staining to localize these proteins in cell cultures. Normal human skin or lung fibroblasts produced a fibrillar pericellular matrix in which fibronectin and procollagen (types I and III) showed extensive codistribution. Fibronectin and procollagen were synthesized by the same cells as judged by double-stain immunofluorescence. Pericellular procollagen was specifically digested with collagenase without an effect on the fibrillar distribution of matrix fibronectin. Brief treatment with trypsin removed both matrix proteins. The human tumor cell lines HT-1080 (fibrosarcoma) and RD (rhabdomyosarcoma) produced little or no matrix fibronectin or procollagen. At sites of cell contact, simian virus 40-transformed lung fibroblasts (VA13) produced small amounts of pericellular fibrillar matrix fibronectin that codistributed with procollagen type I. Intracellular fibronectin and procollagen were visualized in all of these human sarcoma cell lines. When chicken embryo fibroblasts infected with a T class mutant (NY68) of Rous sarcoma virus temperature-sensitive for transformation were maintained at the nonpermissive temperature (41 degrees ) the cells had normal phenotype and a fibrillar matrix containing fibronectin and procollagen was present. At the permissive temperature (35 degrees ), the cells showed transformed phenotype and the matrix was lost. The failure to produce a pericellular fibronectin/collagen matrix may account for several phenotypic characteristics of transformed cultured fibroblasts.", "contents": "Codistribution of pericellular matrix proteins in cultured fibroblasts and loss in transformation: fibronectin and procollagen. Antibodies to fibronectin and to distinct types of procollagens and collagens were used in immunofluorescent staining to localize these proteins in cell cultures. Normal human skin or lung fibroblasts produced a fibrillar pericellular matrix in which fibronectin and procollagen (types I and III) showed extensive codistribution. Fibronectin and procollagen were synthesized by the same cells as judged by double-stain immunofluorescence. Pericellular procollagen was specifically digested with collagenase without an effect on the fibrillar distribution of matrix fibronectin. Brief treatment with trypsin removed both matrix proteins. The human tumor cell lines HT-1080 (fibrosarcoma) and RD (rhabdomyosarcoma) produced little or no matrix fibronectin or procollagen. At sites of cell contact, simian virus 40-transformed lung fibroblasts (VA13) produced small amounts of pericellular fibrillar matrix fibronectin that codistributed with procollagen type I. Intracellular fibronectin and procollagen were visualized in all of these human sarcoma cell lines. When chicken embryo fibroblasts infected with a T class mutant (NY68) of Rous sarcoma virus temperature-sensitive for transformation were maintained at the nonpermissive temperature (41 degrees ) the cells had normal phenotype and a fibrillar matrix containing fibronectin and procollagen was present. At the permissive temperature (35 degrees ), the cells showed transformed phenotype and the matrix was lost. The failure to produce a pericellular fibronectin/collagen matrix may account for several phenotypic characteristics of transformed cultured fibroblasts."}
{"id": "PMID:217007", "title": "Lack of correlation between tumorigenicity and level of plasminogen activator in fibroblasts transformed by Rous sarcoma virus.", "content": "We have previously isolated, from agar suspension culture, clones of chicken embryo fibroblasts transformed by B77 and Prague strains of Rous sarcoma virus (RSV) that varied in the expression of plasminogen activator activity [Wolf, B. A. & Goldberg, A. (1976) Proc. Natl. Acad. Sci. USA 73, 3613-3617]. All of the clones exhibited an altered cellular morphology, an increased rate of sugar transport, and a high efficiency of colony formation in agar suspension regardless of the level of plasminogen activator. Because B77 and Prague strains of RSV replicate as well as cause sarcomas in chickens, the tumorigenicity of the transformed cells could not be evaluated with clones of these cells. In order to determine the oncogenicity of clones with various levels of plasminogen activator, it was necessary to isolate cells transformed by the replication-defective Bryan strain of RSV, which release noninfectious virus. All of the agar suspension clones of transformed cells, derived by infection of chicken embryo cells with replication-defective Bryan RSV, fell within the continuum observed for B77- and Prague-transformed clones with respect to altered morphology, increased rate of sugar transport, efficiency of colony formation in agar suspension, and variations in plasminogen activator activity. All of the clones, regardless of the level of plasminogen activator, produced tumors when as few as 5 x 10(2) cells were injected into the wing web of 1-day-old chicks. The latency period for tumor formation after injection of cells was similar regardless of the level of plasminogen activator of the injected cell. Primary explants of tumors resulting from inoculation of clones having low, intermediate, or high activator activity displayed a spectrum of activator activity.", "contents": "Lack of correlation between tumorigenicity and level of plasminogen activator in fibroblasts transformed by Rous sarcoma virus. We have previously isolated, from agar suspension culture, clones of chicken embryo fibroblasts transformed by B77 and Prague strains of Rous sarcoma virus (RSV) that varied in the expression of plasminogen activator activity [Wolf, B. A. & Goldberg, A. (1976) Proc. Natl. Acad. Sci. USA 73, 3613-3617]. All of the clones exhibited an altered cellular morphology, an increased rate of sugar transport, and a high efficiency of colony formation in agar suspension regardless of the level of plasminogen activator. Because B77 and Prague strains of RSV replicate as well as cause sarcomas in chickens, the tumorigenicity of the transformed cells could not be evaluated with clones of these cells. In order to determine the oncogenicity of clones with various levels of plasminogen activator, it was necessary to isolate cells transformed by the replication-defective Bryan strain of RSV, which release noninfectious virus. All of the agar suspension clones of transformed cells, derived by infection of chicken embryo cells with replication-defective Bryan RSV, fell within the continuum observed for B77- and Prague-transformed clones with respect to altered morphology, increased rate of sugar transport, efficiency of colony formation in agar suspension, and variations in plasminogen activator activity. All of the clones, regardless of the level of plasminogen activator, produced tumors when as few as 5 x 10(2) cells were injected into the wing web of 1-day-old chicks. The latency period for tumor formation after injection of cells was similar regardless of the level of plasminogen activator of the injected cell. Primary explants of tumors resulting from inoculation of clones having low, intermediate, or high activator activity displayed a spectrum of activator activity."}
{"id": "PMID:217008", "title": "Coordinate control of corticotropin, beta-lipotropin, and beta-endorphin release in mouse pituitary cell cultures.", "content": "Hypothalamic extract stimulates the release of corticotropin (ACTH) and endorphins 2.5- to 30-fold in mouse pituitary tumor cell cultures (AtT-20/D(16v) line) and primary cell cultures from mouse anterior pituitary. ACTH and endorphin activities were measured by radioimmunoassay and immunoprecipitation. Pretreatment of tumor cell cultures with 1 muM dexamethasone reduced the stimulatory effect of the extract on release of ACTH and endorphins. Pretreatment of primary cell cultures with 10(-6) M dexamethasone reduced the stimulatory effect of both vasopressin and the extract on the release of ACTH and endorphins. Release of ACTH and endorphin was coupled in both kinds of cultures in the basal, stimulated, and inhibited states. The molecular weight forms of ACTH and endorphin in tumor cell culture medium were analyzed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. Radioimmunoassay and immunoprecipitation show that the 13,000-dalton and 4500-dalton forms of ACTH were present in about equal amounts in medium from cultures incubated with or without hypothalamic extract for 15 min, 30 min, or 2 hr. Smaller amounts of the high molecular weight forms of ACTH (20,000- to 23,000-dalton and 31,000-dalton ACTH) were observed in the culture medium at these times. The predominant forms of endorphin released after 20 min or 3 hr of incubation had molecular weights of 31,000, 11,700 (beta-lipotropic hormone-size material) and 3500 (beta-endorphin-size material). No degradation of the forms of endorphin released into the culture medium was observed after incubating the culture medium for 1.5 hr in the absence of cells. The proportions of the different forms of endorphin and ACTH present in the culture medium resembles that seen in cell extracts.", "contents": "Coordinate control of corticotropin, beta-lipotropin, and beta-endorphin release in mouse pituitary cell cultures. Hypothalamic extract stimulates the release of corticotropin (ACTH) and endorphins 2.5- to 30-fold in mouse pituitary tumor cell cultures (AtT-20/D(16v) line) and primary cell cultures from mouse anterior pituitary. ACTH and endorphin activities were measured by radioimmunoassay and immunoprecipitation. Pretreatment of tumor cell cultures with 1 muM dexamethasone reduced the stimulatory effect of the extract on release of ACTH and endorphins. Pretreatment of primary cell cultures with 10(-6) M dexamethasone reduced the stimulatory effect of both vasopressin and the extract on the release of ACTH and endorphins. Release of ACTH and endorphin was coupled in both kinds of cultures in the basal, stimulated, and inhibited states. The molecular weight forms of ACTH and endorphin in tumor cell culture medium were analyzed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. Radioimmunoassay and immunoprecipitation show that the 13,000-dalton and 4500-dalton forms of ACTH were present in about equal amounts in medium from cultures incubated with or without hypothalamic extract for 15 min, 30 min, or 2 hr. Smaller amounts of the high molecular weight forms of ACTH (20,000- to 23,000-dalton and 31,000-dalton ACTH) were observed in the culture medium at these times. The predominant forms of endorphin released after 20 min or 3 hr of incubation had molecular weights of 31,000, 11,700 (beta-lipotropic hormone-size material) and 3500 (beta-endorphin-size material). No degradation of the forms of endorphin released into the culture medium was observed after incubating the culture medium for 1.5 hr in the absence of cells. The proportions of the different forms of endorphin and ACTH present in the culture medium resembles that seen in cell extracts."}
{"id": "PMID:217009", "title": "Expression of simian virus 40 early genes in transformed rat cells is correlated with maintenance of the transformed phenotype.", "content": "Early viral polypeptides synthesized in simian virus 40 rat transformants were identified by immunoprecipitation using anti-T (tumor) antigen immune serum. Four polypeptide classes could be identified, which were not detectable in extracts of nontransformed cells and were not precipitated from transformed cell extracts by nonimmune serum. Their apparent M(r) were 92,000, 63,000, 56,000, and 19,000. A similar pattern was observed in extracts from lytically infected cells, but the relative rate of radioactive labeling of the M(r) 63,000 and 56,000 species was in this case significantly lower than in transformed cells. In tsA30 transformants of type A, which maintain the transformed phenotype at high temperature, only minor quantitative variations of this pattern were observed when the cultures were shifted from 33 degrees to 40.5 degrees . In contrast, the rate of labeling of the four virus-specific polypeptides was decreased by 90% or more at high temperature in the temperature-sensitive N transformants. In all cases, a coordinated variation of the radioactivity associated with the different polypeptide classes was observed. These results suggest that the synthesis or processing, or both, of the viral early proteins may be controlled by different mechanisms in various types of simian virus 40 transformants and, furthermore, that it may be under the positive control of a virus-coded protein in transformed cells of type N.", "contents": "Expression of simian virus 40 early genes in transformed rat cells is correlated with maintenance of the transformed phenotype. Early viral polypeptides synthesized in simian virus 40 rat transformants were identified by immunoprecipitation using anti-T (tumor) antigen immune serum. Four polypeptide classes could be identified, which were not detectable in extracts of nontransformed cells and were not precipitated from transformed cell extracts by nonimmune serum. Their apparent M(r) were 92,000, 63,000, 56,000, and 19,000. A similar pattern was observed in extracts from lytically infected cells, but the relative rate of radioactive labeling of the M(r) 63,000 and 56,000 species was in this case significantly lower than in transformed cells. In tsA30 transformants of type A, which maintain the transformed phenotype at high temperature, only minor quantitative variations of this pattern were observed when the cultures were shifted from 33 degrees to 40.5 degrees . In contrast, the rate of labeling of the four virus-specific polypeptides was decreased by 90% or more at high temperature in the temperature-sensitive N transformants. In all cases, a coordinated variation of the radioactivity associated with the different polypeptide classes was observed. These results suggest that the synthesis or processing, or both, of the viral early proteins may be controlled by different mechanisms in various types of simian virus 40 transformants and, furthermore, that it may be under the positive control of a virus-coded protein in transformed cells of type N."}
{"id": "PMID:217010", "title": "Reversion of transformed glycolysis to normal by inhibition of protein synthesis in rat kidney cells infected with temperature-sensitive mutant of Rous sarcoma virus.", "content": "Normal rat kidney cells infected with a temperature-sensitive mutant (LA23) of Rous sarcoma virus exhibit the transformed phenotype when grown at 33 degrees and the normal phenotype at 39 degrees. We have previously shown [Ash, J.F., Vogt, P.K. & Singer, S.J. (1976) Proc. Natl. Acad. Sci. USA 73, 3603-3607] that the addition of protein synthesis inhibitors to LA23-infected cells grown at 33 degrees causes them to revert, over a period of 12 hr, to the normal phenotype with respect to morphological and cytoskeletal characteristics. We now show that reversion of the metabolic characteristics of the transformed phenotype to those of the normal also occurs under these conditions. LA23-infected cells show an increased rate of aerobic glycolysis at 33 degrees compared to that at 39 degrees. They also show a different sensitivity of that rate to dinitrophenol and oligomycin at 33 degrees compared to 39 degrees. Such cells grown at 33 degrees in the presence of cycloheximide or abrin rapidly recover the aerobic glycolysis characteristics of the normal phenotype. These results support the thesis that transformation by the src gene of the Rous sarcoma virus is a pleiotypic and reversible process, such as is involved in a pleiotypic enzymic modification reaction and its reversal.", "contents": "Reversion of transformed glycolysis to normal by inhibition of protein synthesis in rat kidney cells infected with temperature-sensitive mutant of Rous sarcoma virus. Normal rat kidney cells infected with a temperature-sensitive mutant (LA23) of Rous sarcoma virus exhibit the transformed phenotype when grown at 33 degrees and the normal phenotype at 39 degrees. We have previously shown [Ash, J.F., Vogt, P.K. & Singer, S.J. (1976) Proc. Natl. Acad. Sci. USA 73, 3603-3607] that the addition of protein synthesis inhibitors to LA23-infected cells grown at 33 degrees causes them to revert, over a period of 12 hr, to the normal phenotype with respect to morphological and cytoskeletal characteristics. We now show that reversion of the metabolic characteristics of the transformed phenotype to those of the normal also occurs under these conditions. LA23-infected cells show an increased rate of aerobic glycolysis at 33 degrees compared to that at 39 degrees. They also show a different sensitivity of that rate to dinitrophenol and oligomycin at 33 degrees compared to 39 degrees. Such cells grown at 33 degrees in the presence of cycloheximide or abrin rapidly recover the aerobic glycolysis characteristics of the normal phenotype. These results support the thesis that transformation by the src gene of the Rous sarcoma virus is a pleiotypic and reversible process, such as is involved in a pleiotypic enzymic modification reaction and its reversal."}
{"id": "PMID:217011", "title": "Receptor-mediated uptake of low density lipoprotein reconstituted with 25-hydroxycholesteryl oleate suppresses 3-hydroxy-3-methylglutaryl-coenzyme A reductase and inhibits growth of human fibroblasts.", "content": "The free and esterified cholesterols of plasma low density lipoprotein (LDL) were extracted with heptane and replaced with 25-hydroxycholesteryl oleate. The resulting particle, designated r-[25-HC oleate]LDL, bound to LDL receptors on human fibroblasts, was taken up by adsorptive endocytosis and was hydrolyzed in lysosomes in a manner similar to that of native LDL. The r-[25-HC oleate]LDL suppressed 3-hydroxy-3-methylglutaryl-coenzyme A reductase [mevalonate:NADP(+) oxidoreductase (CoA-acylating), EC 1.1.1.34], the enzyme catalyzing the rate-limiting step in cholesterol biosynthesis. This suppression did not occur when lysosomal hydrolysis of r-[25-HC oleate]LDL was inhibited by chloroquine. When fibroblasts were incubated with r-[25-HC oleate]LDL in the absence of a source of cholesterol, the cells developed an abnormal morphology, their growth was inhibited, and the cells died. The toxic effects of r-[25-HC oleate]LDL were prevented when the growth medium was supplemented with cholesterol in ethanol or with mevalonate, the product of the reductase reaction. These data suggest that the toxicity of r-[25-HC oleate]LDL was due to its suppression of reductase, which in turn caused cellular cholesterol deficiency. The r-[25-HC oleate]LDL did not suppress reductase activity nor did it alter the growth or morphology of mutant fibroblasts lacking LDL receptors, which were obtained from a patient with homozygous familial hypercholesterolemia. These experiments demonstrate the feasibility of using reconstituted LDL to selectively deliver hydrophobic compounds other than typical cholesteryl esters to cells possessing LDL receptors.", "contents": "Receptor-mediated uptake of low density lipoprotein reconstituted with 25-hydroxycholesteryl oleate suppresses 3-hydroxy-3-methylglutaryl-coenzyme A reductase and inhibits growth of human fibroblasts. The free and esterified cholesterols of plasma low density lipoprotein (LDL) were extracted with heptane and replaced with 25-hydroxycholesteryl oleate. The resulting particle, designated r-[25-HC oleate]LDL, bound to LDL receptors on human fibroblasts, was taken up by adsorptive endocytosis and was hydrolyzed in lysosomes in a manner similar to that of native LDL. The r-[25-HC oleate]LDL suppressed 3-hydroxy-3-methylglutaryl-coenzyme A reductase [mevalonate:NADP(+) oxidoreductase (CoA-acylating), EC 1.1.1.34], the enzyme catalyzing the rate-limiting step in cholesterol biosynthesis. This suppression did not occur when lysosomal hydrolysis of r-[25-HC oleate]LDL was inhibited by chloroquine. When fibroblasts were incubated with r-[25-HC oleate]LDL in the absence of a source of cholesterol, the cells developed an abnormal morphology, their growth was inhibited, and the cells died. The toxic effects of r-[25-HC oleate]LDL were prevented when the growth medium was supplemented with cholesterol in ethanol or with mevalonate, the product of the reductase reaction. These data suggest that the toxicity of r-[25-HC oleate]LDL was due to its suppression of reductase, which in turn caused cellular cholesterol deficiency. The r-[25-HC oleate]LDL did not suppress reductase activity nor did it alter the growth or morphology of mutant fibroblasts lacking LDL receptors, which were obtained from a patient with homozygous familial hypercholesterolemia. These experiments demonstrate the feasibility of using reconstituted LDL to selectively deliver hydrophobic compounds other than typical cholesteryl esters to cells possessing LDL receptors."}
{"id": "PMID:217012", "title": "Translocation of a hydrocarbon fluorescent probe between Epstein-Barr virus and lymphoid cells: an assay for early events in viral infection.", "content": "Translocation of the hydrocarbon fluorescent probe diphenylhexatriene (DPH) between membranes was studied by fluorescence polarization (P) analysis. First, using a model system, the high P value (0.324) of DPH-labeled cholesterol/phosphatidylcholine liposomes and the low P value (0.157) of DPH-labeled phosphatidylcholine liposomes allowed detection of DPH translocation between interacting liposomes. This was monitored by the change in P in either direction. Early events during cell-virus interactions were similarly studied by monitoring DPH translocation. The P value of DPH-labeled Epstein-Barr Virus (EBV) was significantly higher (0.350-0.392) than the P value of DPH-labeled lymphoid cells (0.238-0.289). Hence, DPH translocation could be detected by changes in P following incubation of DPH-labeled EBV and nonlabeled cells. A marked decrease in P was observed after incubation of DPH-labeled EBV with either nonlabeled lymphoblastoid Raji cells or fresh human B lymphocytes. However, only a slight decrease in P was obtained when DPH-labeled EBV was incubated with either nonlabeled fresh human T lymphocytes or fresh T or B rabbit lymphocytes. Moreover, incubation of fresh human B lymphocytes with the purified C3 component of complement (a putative inhibitor for the EBV receptor) prior to the addition of DPH-labeled EBV abolished the observed decrease in the P value. Most of these experiments were carried out with both the P3HR-1 and the B95-8 strains of EBV. DPH translocation, as determined by fluorescence polarization analysis, is, therefore, measuring some early event during interaction of this enveloped virus and mammalian cells. The potential applicability of this technique to other viruses is illustrated by an experiment with Semliki Forest virus.", "contents": "Translocation of a hydrocarbon fluorescent probe between Epstein-Barr virus and lymphoid cells: an assay for early events in viral infection. Translocation of the hydrocarbon fluorescent probe diphenylhexatriene (DPH) between membranes was studied by fluorescence polarization (P) analysis. First, using a model system, the high P value (0.324) of DPH-labeled cholesterol/phosphatidylcholine liposomes and the low P value (0.157) of DPH-labeled phosphatidylcholine liposomes allowed detection of DPH translocation between interacting liposomes. This was monitored by the change in P in either direction. Early events during cell-virus interactions were similarly studied by monitoring DPH translocation. The P value of DPH-labeled Epstein-Barr Virus (EBV) was significantly higher (0.350-0.392) than the P value of DPH-labeled lymphoid cells (0.238-0.289). Hence, DPH translocation could be detected by changes in P following incubation of DPH-labeled EBV and nonlabeled cells. A marked decrease in P was observed after incubation of DPH-labeled EBV with either nonlabeled lymphoblastoid Raji cells or fresh human B lymphocytes. However, only a slight decrease in P was obtained when DPH-labeled EBV was incubated with either nonlabeled fresh human T lymphocytes or fresh T or B rabbit lymphocytes. Moreover, incubation of fresh human B lymphocytes with the purified C3 component of complement (a putative inhibitor for the EBV receptor) prior to the addition of DPH-labeled EBV abolished the observed decrease in the P value. Most of these experiments were carried out with both the P3HR-1 and the B95-8 strains of EBV. DPH translocation, as determined by fluorescence polarization analysis, is, therefore, measuring some early event during interaction of this enveloped virus and mammalian cells. The potential applicability of this technique to other viruses is illustrated by an experiment with Semliki Forest virus."}
{"id": "PMID:217013", "title": "Biological significance of alloreactivity: T cells stimulated by Sendai virus-coated syngeneic cells specifically lyse allogeneic target cells.", "content": "In vitro stimulation of spleen cells from mice immune to Sendai virus results in the generation of effector cells that lyse unmodified allogeneic target cells in addition to syngeneic cells modified by virus. These cells are immunologically specific because their lysis may be blocked by cold targets syngeneic to either the stimulator or the responder. These results support our proposal that the development of alloreactivity can be explained by the crossreactivity between modified self major histocompatibility complex antigens and alloantigens. We propose that exposure to autologous major histocompatibility complex antigens modified by foreign antigens in our environment results in the expansion of the pool of T cells that will respond to alloantigens sharing crossreactive determinants.", "contents": "Biological significance of alloreactivity: T cells stimulated by Sendai virus-coated syngeneic cells specifically lyse allogeneic target cells. In vitro stimulation of spleen cells from mice immune to Sendai virus results in the generation of effector cells that lyse unmodified allogeneic target cells in addition to syngeneic cells modified by virus. These cells are immunologically specific because their lysis may be blocked by cold targets syngeneic to either the stimulator or the responder. These results support our proposal that the development of alloreactivity can be explained by the crossreactivity between modified self major histocompatibility complex antigens and alloantigens. We propose that exposure to autologous major histocompatibility complex antigens modified by foreign antigens in our environment results in the expansion of the pool of T cells that will respond to alloantigens sharing crossreactive determinants."}
{"id": "PMID:217014", "title": "Epstein-Barr virus and human chromosomes: close association of the resident viral genome and the expression of the virus-determined nuclear antigen (EBNA) with the presence of chromosome 14 in human-mouse hybrid cells.", "content": "Fourteen hybrid clones derived from the fused cultures of human lymphoblastoid FV5 cells and 5-bromodeoxyuridine-resistant mouse fibroblastic MCB2 cells grown in hypoxanthine/aminopterin/thymidine selective medium were examined for the presence of Epstein-Barr virus (EBV) DNA, the expression of the virus-determined nuclear antigen (EBNA), and the presence of human chromosomes, in the course of serial passage in vitro. Among the hybrid clones tested, 3 were positive for EBV DNA and EBNA, whereas the remaining 11 were totally negative. The chromosome investigations showed that human chromosome 14 was consistently involved in all three EBV genome-positive and EBNA-positive hybrid clones, but not in any negative clones. In 10 subclones isolated from 1 of the 3 positive clones, all of which contained only chromosome 14 of the human chromosomes, a concordant segregation of EBNA, EBA DNA, and chromosome 14 was evident. These findings suggest that the resident EBV genome is closely associated with chromosome 14 and the presence of this particular chromosome alone is sufficient for the maintenance and the expression of EBV genetic information in human lymphoblastoid cells.", "contents": "Epstein-Barr virus and human chromosomes: close association of the resident viral genome and the expression of the virus-determined nuclear antigen (EBNA) with the presence of chromosome 14 in human-mouse hybrid cells. Fourteen hybrid clones derived from the fused cultures of human lymphoblastoid FV5 cells and 5-bromodeoxyuridine-resistant mouse fibroblastic MCB2 cells grown in hypoxanthine/aminopterin/thymidine selective medium were examined for the presence of Epstein-Barr virus (EBV) DNA, the expression of the virus-determined nuclear antigen (EBNA), and the presence of human chromosomes, in the course of serial passage in vitro. Among the hybrid clones tested, 3 were positive for EBV DNA and EBNA, whereas the remaining 11 were totally negative. The chromosome investigations showed that human chromosome 14 was consistently involved in all three EBV genome-positive and EBNA-positive hybrid clones, but not in any negative clones. In 10 subclones isolated from 1 of the 3 positive clones, all of which contained only chromosome 14 of the human chromosomes, a concordant segregation of EBNA, EBA DNA, and chromosome 14 was evident. These findings suggest that the resident EBV genome is closely associated with chromosome 14 and the presence of this particular chromosome alone is sufficient for the maintenance and the expression of EBV genetic information in human lymphoblastoid cells."}
{"id": "PMID:217015", "title": "Corticotropin, lipotropin, and beta-endorphin production by a human nonpituitary tumor in culture: evidence for a common precursor.", "content": "A continuous line (DMS-79) of human pulmonary small cell carcinoma cells was shown to secrete immunoreactive adrenocorticotropin (ACTH), lipotropin, and beta-endorphin concomitantly into the culture medium. Gel filtration of the culture medium demonstrated at least five components: high molecular weight material(s) that had ACTH, lipotropin, and beta-endorphin immunoreactivities and materials similar to ACTH, beta-lipotropin, gamma-lipotropin, and beta-endorphin in their immunoreactivities and apparent molecular weights. The same components were observed when gel filtration was carried out in 6 M guanidine-HCl, and the high molecular weight material(s) appeared to consist of more than one component, with molecular weights in the range of 15,000-40,000. Immune affinity chromatography of the high molecular weight component(s) from gel filtration with a specific anti-(1-24)ACTH serum demonstrated that the ACTH, lipotropin, and beta-endorphin immunoreactivities were possessed by the same molecule(s), suggesting that ACTH, lipotropins, and beta-endorphin were derived from a common, high molecular weight precursor.", "contents": "Corticotropin, lipotropin, and beta-endorphin production by a human nonpituitary tumor in culture: evidence for a common precursor. A continuous line (DMS-79) of human pulmonary small cell carcinoma cells was shown to secrete immunoreactive adrenocorticotropin (ACTH), lipotropin, and beta-endorphin concomitantly into the culture medium. Gel filtration of the culture medium demonstrated at least five components: high molecular weight material(s) that had ACTH, lipotropin, and beta-endorphin immunoreactivities and materials similar to ACTH, beta-lipotropin, gamma-lipotropin, and beta-endorphin in their immunoreactivities and apparent molecular weights. The same components were observed when gel filtration was carried out in 6 M guanidine-HCl, and the high molecular weight material(s) appeared to consist of more than one component, with molecular weights in the range of 15,000-40,000. Immune affinity chromatography of the high molecular weight component(s) from gel filtration with a specific anti-(1-24)ACTH serum demonstrated that the ACTH, lipotropin, and beta-endorphin immunoreactivities were possessed by the same molecule(s), suggesting that ACTH, lipotropins, and beta-endorphin were derived from a common, high molecular weight precursor."}
{"id": "PMID:217016", "title": "Neurotransmitter modulation, phosphodiesterase inhibitor effects, and cyclic AMP correlates of afterdischarge in peptidergic neurites.", "content": "The neuroendocrine bag cells in the abdominal ganglion of Aplysia generate a long-lasting synchronous afterdischarge upon brief stimulation of an afferent pathway. After this afterdischarge the cells become refractory to further synaptic stimulation. We find that synchrony, afterdischarge, and prolonged refractoriness are properties that can be expressed in the isolated asomatic neurites of the bag cells. We have distinguished two independent types of refractoriness. The first (type I) is seen as a failure of action potentials generated in the tips of bag cell neurites to invade cell somata. The second form of refractoriness (type II) controls the duration of afterdischarge such that stimuli after the first afterdischarge produce only very short afterdischarges or fail to elicit an afterdischarge. Type II refractoriness is sensitive to serotonin and certain of its analogues, and to dopamine and the methylxanthine phosphodiesterase inhibitors. Extracellularly applied serotonin suppresses an ongoing afterdischarge while dopamine and the phosphodiesterase inhibitors, when applied at the end of the first afterdischarge, generate a subsequent afterdischarge of long duration without further electrical stimulation. None of these compounds influenced the degree of type I refractoriness. We have shown that both serotonin and dopamine stimulate the formation of cyclic AMP in the bag cell clusters and in the pleurovisceral connectives and that the occurrence of an afterdischarge is associated with a specific increase in total cyclic AMP in bag cell bodies. Moreover, afterdischarges can be generated in unstimulated preparations by extracellular application of the cyclic AMP analogues, 8-benzylthio-cyclic AMP or 8-methylthio-cyclic AMP. Our data suggest that serotonin and/or dopamine may control bag cell activity and that activation of adenylate cyclase is linked to bag cell afterdischarge.", "contents": "Neurotransmitter modulation, phosphodiesterase inhibitor effects, and cyclic AMP correlates of afterdischarge in peptidergic neurites. The neuroendocrine bag cells in the abdominal ganglion of Aplysia generate a long-lasting synchronous afterdischarge upon brief stimulation of an afferent pathway. After this afterdischarge the cells become refractory to further synaptic stimulation. We find that synchrony, afterdischarge, and prolonged refractoriness are properties that can be expressed in the isolated asomatic neurites of the bag cells. We have distinguished two independent types of refractoriness. The first (type I) is seen as a failure of action potentials generated in the tips of bag cell neurites to invade cell somata. The second form of refractoriness (type II) controls the duration of afterdischarge such that stimuli after the first afterdischarge produce only very short afterdischarges or fail to elicit an afterdischarge. Type II refractoriness is sensitive to serotonin and certain of its analogues, and to dopamine and the methylxanthine phosphodiesterase inhibitors. Extracellularly applied serotonin suppresses an ongoing afterdischarge while dopamine and the phosphodiesterase inhibitors, when applied at the end of the first afterdischarge, generate a subsequent afterdischarge of long duration without further electrical stimulation. None of these compounds influenced the degree of type I refractoriness. We have shown that both serotonin and dopamine stimulate the formation of cyclic AMP in the bag cell clusters and in the pleurovisceral connectives and that the occurrence of an afterdischarge is associated with a specific increase in total cyclic AMP in bag cell bodies. Moreover, afterdischarges can be generated in unstimulated preparations by extracellular application of the cyclic AMP analogues, 8-benzylthio-cyclic AMP or 8-methylthio-cyclic AMP. Our data suggest that serotonin and/or dopamine may control bag cell activity and that activation of adenylate cyclase is linked to bag cell afterdischarge."}
{"id": "PMID:217017", "title": "L-aspartate: evidence for a role in cone photoreceptor synaptic transmission in the carp retina.", "content": "A number of putative neurotransmitter substances and their antagonists were applied to the carp retina while intracellular recordings from L-type cone horizontal cells were made. Of all the substances tested, L-aspartate was found to be the most potent agent in depolarizing these horizontal cells in dark-adapted, partially light-adapted, and Co2+-treated retinas. Furthermore, DL-alpha-aminoadipate, an L-aspartate antagonist, blocked the effects of both the endogenous photoreceptor transmitter and exogenously applied L-aspartate on the horizontal cells. The results suggest that L-aspartate and the natural transmitter interact with the same population of postsynaptic receptors in the horizontal cell membrane.", "contents": "L-aspartate: evidence for a role in cone photoreceptor synaptic transmission in the carp retina. A number of putative neurotransmitter substances and their antagonists were applied to the carp retina while intracellular recordings from L-type cone horizontal cells were made. Of all the substances tested, L-aspartate was found to be the most potent agent in depolarizing these horizontal cells in dark-adapted, partially light-adapted, and Co2+-treated retinas. Furthermore, DL-alpha-aminoadipate, an L-aspartate antagonist, blocked the effects of both the endogenous photoreceptor transmitter and exogenously applied L-aspartate on the horizontal cells. The results suggest that L-aspartate and the natural transmitter interact with the same population of postsynaptic receptors in the horizontal cell membrane."}
{"id": "PMID:217018", "title": "Induction of neurite outgrowth by a conditioned-medium factor bound to the culture substratum.", "content": "Heart-cell conditioned medium (HCM) induces rapid neurite outgrowth from isolated neurons in culture. The following evidence indicates that this action of HCM is due to a trypsin-sensitive factor which attaches to the polyornithinecoated culture substratum: (i) Pretreatment of the culture substratum with HCM allows rapid neurite outgrowth to occur even in unconditioned media. The active factor remains bound to the substratum during the period of neurite outgrowth. (ii) The substratum-bound activity is destroyed by trypsin treatment, but is insensitive to collagenase, RNase, and DNase. (iii) The factor that binds to the substratum is essential for neurite outgrowth, because HCM is no longer active when the material that binds to the polyornithine substratum has been removed by passage of the HCM over a series of culture dishes. However, this \"depleted\" HCM is still able to support the growth of nonneuronal cells. (iv) Most significantly, when neurons are cultured in whole HCM, the extent of neurite outgrowth is proportional to the amount of substratum-bound activity and not to the amount in solution, indicating that the substratum-bound form of the factor is more active. Previous observations [Collins, F. (1978) Dev. Biol. 65, 50-57] suggest that HCM promotes neurite outgrowth by increasing the adhesion between nerve cell surface extensions and the polyornithine-coated culture substratum. It is possible, therefore, that the factor in HCM that binds to the substratum possesses sites to which nerve cell surface components adhere.", "contents": "Induction of neurite outgrowth by a conditioned-medium factor bound to the culture substratum. Heart-cell conditioned medium (HCM) induces rapid neurite outgrowth from isolated neurons in culture. The following evidence indicates that this action of HCM is due to a trypsin-sensitive factor which attaches to the polyornithinecoated culture substratum: (i) Pretreatment of the culture substratum with HCM allows rapid neurite outgrowth to occur even in unconditioned media. The active factor remains bound to the substratum during the period of neurite outgrowth. (ii) The substratum-bound activity is destroyed by trypsin treatment, but is insensitive to collagenase, RNase, and DNase. (iii) The factor that binds to the substratum is essential for neurite outgrowth, because HCM is no longer active when the material that binds to the polyornithine substratum has been removed by passage of the HCM over a series of culture dishes. However, this \"depleted\" HCM is still able to support the growth of nonneuronal cells. (iv) Most significantly, when neurons are cultured in whole HCM, the extent of neurite outgrowth is proportional to the amount of substratum-bound activity and not to the amount in solution, indicating that the substratum-bound form of the factor is more active. Previous observations [Collins, F. (1978) Dev. Biol. 65, 50-57] suggest that HCM promotes neurite outgrowth by increasing the adhesion between nerve cell surface extensions and the polyornithine-coated culture substratum. It is possible, therefore, that the factor in HCM that binds to the substratum possesses sites to which nerve cell surface components adhere."}
{"id": "PMID:217019", "title": "Cyclic GMP injected into retinal rod outer segments increases latency and amplitude of response to illumination.", "content": "We have injected cyclic GMP intracellularly by iontophoresis through the recording electrode into single rod outer segments of the isolated superfused retina of the toad. Bufo marinus. The two most marked effects of the injection are: (i) the latency of the hyperpolarizing membrane-potential change caused by illumination is increased from 5 to 50 times normal, the increase in latency being inversely proportional to the light stimulus intensity; and (ii) the amplitude of the hyperpolarizing receptor potential is increased. These effects are reversible. Our findings are consistent with the hypothesis that cyclic GMP is a link in the molecular chain of events that controls the inward flow of sodium ions in light and darkness. The increased latency we observe after injection of cyclic GMP may be caused by a time delay necessary for light-activated phosphodiesterase to hydrolyze the excess cyclic GMP. By this reasoning the excess cyclic GMP perpetuates the dark current long after illumination. Excitation may be controlled by cyclic GMP if, as our experiments suggest, its hydrolysis initiates the hyperpolarizing receptor potential.", "contents": "Cyclic GMP injected into retinal rod outer segments increases latency and amplitude of response to illumination. We have injected cyclic GMP intracellularly by iontophoresis through the recording electrode into single rod outer segments of the isolated superfused retina of the toad. Bufo marinus. The two most marked effects of the injection are: (i) the latency of the hyperpolarizing membrane-potential change caused by illumination is increased from 5 to 50 times normal, the increase in latency being inversely proportional to the light stimulus intensity; and (ii) the amplitude of the hyperpolarizing receptor potential is increased. These effects are reversible. Our findings are consistent with the hypothesis that cyclic GMP is a link in the molecular chain of events that controls the inward flow of sodium ions in light and darkness. The increased latency we observe after injection of cyclic GMP may be caused by a time delay necessary for light-activated phosphodiesterase to hydrolyze the excess cyclic GMP. By this reasoning the excess cyclic GMP perpetuates the dark current long after illumination. Excitation may be controlled by cyclic GMP if, as our experiments suggest, its hydrolysis initiates the hyperpolarizing receptor potential."}
{"id": "PMID:217027", "title": "Perspectives on central nervous system responsiveness to transcutaneous electrical nerve stimulation.", "content": "This review article is designed to further enlighten the physical therapist about pathways transmitting nociceptive information and about systems capable of inhibiting this transmission. At present, little information exists to explain how transcutaneous electrical nerve stimulation effects changes in pain perception. Contemporary knowledge regarding proposed modes of action for this modality is presented in light of current neurophysiological information. In explaining the action of transcutaneous electrical nerve stimulation, alternatives to the gate-control theory of pain are suggested as being quite possible. Questions regarding future investigations are proposed.", "contents": "Perspectives on central nervous system responsiveness to transcutaneous electrical nerve stimulation. This review article is designed to further enlighten the physical therapist about pathways transmitting nociceptive information and about systems capable of inhibiting this transmission. At present, little information exists to explain how transcutaneous electrical nerve stimulation effects changes in pain perception. Contemporary knowledge regarding proposed modes of action for this modality is presented in light of current neurophysiological information. In explaining the action of transcutaneous electrical nerve stimulation, alternatives to the gate-control theory of pain are suggested as being quite possible. Questions regarding future investigations are proposed."}
{"id": "PMID:217028", "title": "Introduction to the use of transcutaneous electrical nerve stimulation devices.", "content": "Transcutaneous electrical nerve stimulation is an ancient but newly discovered modality. Initially intended for use in chronic pain syndromes, transcutaneous electrical nerve stimulation may be even more useful in managing acute pain. Although procedures for the use of this device are relatively simple, additional knowledge about selecting and adjusting the device as well as clinical experience will largely determine the degree of success obtained with this modality. Adjusting transcutaneous electrical nerve stimulation units can alter the stimulus efficiency. No one wave-form is the most effective, but characteristics of effective wave-forms are known. In addition, the patient must be knowledgeable and cooperative when transcutaneous electrical nerve stimulation is applied.", "contents": "Introduction to the use of transcutaneous electrical nerve stimulation devices. Transcutaneous electrical nerve stimulation is an ancient but newly discovered modality. Initially intended for use in chronic pain syndromes, transcutaneous electrical nerve stimulation may be even more useful in managing acute pain. Although procedures for the use of this device are relatively simple, additional knowledge about selecting and adjusting the device as well as clinical experience will largely determine the degree of success obtained with this modality. Adjusting transcutaneous electrical nerve stimulation units can alter the stimulus efficiency. No one wave-form is the most effective, but characteristics of effective wave-forms are known. In addition, the patient must be knowledgeable and cooperative when transcutaneous electrical nerve stimulation is applied."}
{"id": "PMID:217029", "title": "Peripheral neural excitability. Implications for transcutaneous electrical nerve stimulation.", "content": "Basic neurophysiological principles necessary for understanding the effectiveness of transcutaneous electrical nerve stimulation are presented. Peripheral and central neural mechanisms are reviewed, and the effects of individual pulse characteristics on neural excitability are analyzed. Representative commercial stimulators are compared, and wave-forms for different load conditions are illustrated. Discussion includes important considerations for clinical effectiveness and for patient acceptance and safety.", "contents": "Peripheral neural excitability. Implications for transcutaneous electrical nerve stimulation. Basic neurophysiological principles necessary for understanding the effectiveness of transcutaneous electrical nerve stimulation are presented. Peripheral and central neural mechanisms are reviewed, and the effects of individual pulse characteristics on neural excitability are analyzed. Representative commercial stimulators are compared, and wave-forms for different load conditions are illustrated. Discussion includes important considerations for clinical effectiveness and for patient acceptance and safety."}
{"id": "PMID:217030", "title": "[Neurogenic claudication and claudication by arteritis of the lower limbs].", "content": "Intermittent claudication of neurogenic origin can be traced to three basic causes: --either a chronic circulatory deficiency in the arteries leading to the spinal cord, whether these arteries be the site of an atheroma of the ostia, an inflammation or a loco-regional compression. In such cases, the claudication is painless which differentiates it from the arteritis claudication of the lower limbs. --or to a compression of the roots of the cauda equina and to a lesser degree of the spinal cord, through a narrow rachidian canal that is hereditary or acquired, and relative or absolute. --or finally to a sheathing peripheral neuropathy of the lower limbs. The two latter causes are accompanied by pain, and make it necessary to widen the classical notion of the intermittent claudication (Dejerine's non painful intermittent claudication of the spinal cord).", "contents": "[Neurogenic claudication and claudication by arteritis of the lower limbs]. Intermittent claudication of neurogenic origin can be traced to three basic causes: --either a chronic circulatory deficiency in the arteries leading to the spinal cord, whether these arteries be the site of an atheroma of the ostia, an inflammation or a loco-regional compression. In such cases, the claudication is painless which differentiates it from the arteritis claudication of the lower limbs. --or to a compression of the roots of the cauda equina and to a lesser degree of the spinal cord, through a narrow rachidian canal that is hereditary or acquired, and relative or absolute. --or finally to a sheathing peripheral neuropathy of the lower limbs. The two latter causes are accompanied by pain, and make it necessary to widen the classical notion of the intermittent claudication (Dejerine's non painful intermittent claudication of the spinal cord)."}
{"id": "PMID:217031", "title": "[Kaposi's disease and venous insufficiency].", "content": "This case involves a 28-year-old man suffering from severe circulatory failure with blue and cold limbs resulting from childhood polio and showing circumscribed plaques of angio-dermatitis (Favre and Chaix) with a tumor-like appearance resembling Kaposi's angiosarcomatosis. These facts described by Mali in circulatory ailments, especially following phlebitis, should be known to phlebologists. They differ from Kaposi-like disease by the much rarer arterio-venous fistula (described by Bluefarb and Stewart). It is possible that there are mixed forms and that the cases attributed to simple circulatory failure may be due to the minimal linkage of arterio-venous fistulas that can be detected only by arterio-selection.", "contents": "[Kaposi's disease and venous insufficiency]. This case involves a 28-year-old man suffering from severe circulatory failure with blue and cold limbs resulting from childhood polio and showing circumscribed plaques of angio-dermatitis (Favre and Chaix) with a tumor-like appearance resembling Kaposi's angiosarcomatosis. These facts described by Mali in circulatory ailments, especially following phlebitis, should be known to phlebologists. They differ from Kaposi-like disease by the much rarer arterio-venous fistula (described by Bluefarb and Stewart). It is possible that there are mixed forms and that the cases attributed to simple circulatory failure may be due to the minimal linkage of arterio-venous fistulas that can be detected only by arterio-selection."}
{"id": "PMID:217041", "title": "[Cholangiocarcinoma in a patient with hepatosplenic atrophy subsequent to thorotrast administration (author's transl)].", "content": "A case of cholangiocarcinoma observed in a woman of 38 following carotidographic examination with Thorotrast is described: the presence of radioactivity was also demonstrated by gamma spectrometry. The high mean dose absorbed by the liver (estimated at about 3,000 rad) together with the high relative biological effectiveness of the alpha contribution and the time lapse justify the hypothesis that the neoplasia was caused by irradiation.", "contents": "[Cholangiocarcinoma in a patient with hepatosplenic atrophy subsequent to thorotrast administration (author's transl)]. A case of cholangiocarcinoma observed in a woman of 38 following carotidographic examination with Thorotrast is described: the presence of radioactivity was also demonstrated by gamma spectrometry. The high mean dose absorbed by the liver (estimated at about 3,000 rad) together with the high relative biological effectiveness of the alpha contribution and the time lapse justify the hypothesis that the neoplasia was caused by irradiation."}
{"id": "PMID:217049", "title": "Stress simulation: ACTH and zinc effect on trace metals in liver and spleen.", "content": "Effect of ACTH and zinc acetate subcutaneous injection on the trace metals in liver and spleen was investigated in male Wistar rats. Iron, copper, zinc and manganese in liver, and iron, copper and zinc in spleen were analyzed by AAS method. The iron, copper and zinc levels in liver, and iron levels in spleen showed a significant decrease at 1-1 h 30 min after administration of 30 UI of ACTH but values returned to normality or showed slightly higher levels at 4 h 30 min-7 h 45 min. Zinc acetate injection only elicited an increase in liver and spleen zinc levels. Results are discussed in relation with results given in previous papers.", "contents": "Stress simulation: ACTH and zinc effect on trace metals in liver and spleen. Effect of ACTH and zinc acetate subcutaneous injection on the trace metals in liver and spleen was investigated in male Wistar rats. Iron, copper, zinc and manganese in liver, and iron, copper and zinc in spleen were analyzed by AAS method. The iron, copper and zinc levels in liver, and iron levels in spleen showed a significant decrease at 1-1 h 30 min after administration of 30 UI of ACTH but values returned to normality or showed slightly higher levels at 4 h 30 min-7 h 45 min. Zinc acetate injection only elicited an increase in liver and spleen zinc levels. Results are discussed in relation with results given in previous papers."}
{"id": "PMID:217050", "title": "Pathobiology of cortical neurons in metabolic and unclassified amentias.", "content": "Visualization of the neuron in its entirety through the use of the rapid Golgi method has permitted detection of several pathobiological features of neurons that are intimately associated with profound mental retardation in infants and children. In cases of unclassified mental retardation, dendrites and particularly dendritic spines exhibit severe developmental abnormalities. Dendritic spines, the postsynaptic components of axospinodendritic synapses, may be absent or abnormally long and thin in retardates. Evidence is presented that some cases of progressive neurobehavioral deterioration in infancy and early childhood may be due to progressive degeneration of dendritic spine systems (dendritic spine \"dysgenesis\"). Golgi and electron microscopic studies of neurons in human and feline ganglioside storage diseases indicate that ganglioside accumulation in cortical neurons initiates several complex alterations in neuronal geometry and morphology. Small and medium pyramidal cells form massive structural compartments (meganeurites) that frequently give rise to secondary neurites and other embryonic growth processes. Meganeurites may possess spines and spine-synapses. Other cells such as large pyramidal neurons may exhibit many somatic spines, whereas intrinsic cells of the cortex (and caudate) are unaffected morphologically by ganglioside accumulation. It is suggested that neuronal geometry distortion and aberrant synaptogenesis are important factors in the onset of neuronal dysfunction in ganglioside storage disorders. These studies also point to an important role of gangliosides in neurite formation in immature mammalian cortical neurons. Perisomatic processes and somatic spines are normal morphological components of the cell body of Purkinje cells through the 28th fetal week of human gestation. By 36 weeks the Purkinje cell somas exhibit a smooth surface contour. Prominent polydendritic processes, perisomatic protuberances, and somatic spines are detectable by Golgi methods applied to Purkinje cells in Menkes' disease and Down's syndrome long after these somatic components should normally disappear. Thus Purkinje cell soma membrane differentiation is a particularly sensitive process that can provide information on mechanisms of site-specific membrane regulation.", "contents": "Pathobiology of cortical neurons in metabolic and unclassified amentias. Visualization of the neuron in its entirety through the use of the rapid Golgi method has permitted detection of several pathobiological features of neurons that are intimately associated with profound mental retardation in infants and children. In cases of unclassified mental retardation, dendrites and particularly dendritic spines exhibit severe developmental abnormalities. Dendritic spines, the postsynaptic components of axospinodendritic synapses, may be absent or abnormally long and thin in retardates. Evidence is presented that some cases of progressive neurobehavioral deterioration in infancy and early childhood may be due to progressive degeneration of dendritic spine systems (dendritic spine \"dysgenesis\"). Golgi and electron microscopic studies of neurons in human and feline ganglioside storage diseases indicate that ganglioside accumulation in cortical neurons initiates several complex alterations in neuronal geometry and morphology. Small and medium pyramidal cells form massive structural compartments (meganeurites) that frequently give rise to secondary neurites and other embryonic growth processes. Meganeurites may possess spines and spine-synapses. Other cells such as large pyramidal neurons may exhibit many somatic spines, whereas intrinsic cells of the cortex (and caudate) are unaffected morphologically by ganglioside accumulation. It is suggested that neuronal geometry distortion and aberrant synaptogenesis are important factors in the onset of neuronal dysfunction in ganglioside storage disorders. These studies also point to an important role of gangliosides in neurite formation in immature mammalian cortical neurons. Perisomatic processes and somatic spines are normal morphological components of the cell body of Purkinje cells through the 28th fetal week of human gestation. By 36 weeks the Purkinje cell somas exhibit a smooth surface contour. Prominent polydendritic processes, perisomatic protuberances, and somatic spines are detectable by Golgi methods applied to Purkinje cells in Menkes' disease and Down's syndrome long after these somatic components should normally disappear. Thus Purkinje cell soma membrane differentiation is a particularly sensitive process that can provide information on mechanisms of site-specific membrane regulation."}
{"id": "PMID:217052", "title": "Gas exchange abnormalities produced by venous gas emboli.", "content": "Bubbles of either He, N2 or SF6 were infused intravenously into anesthetized dogs at a rate of 0.2 ml/kg/min. Alterations in pulmonary gas exchange were quantitated by the invert gas elimination method during control, steady state infusion and resolution phases. The hypoxemia produced was predominantly due to regions of low VA/Q rather than pure shunt, and the increase in physiological dead space was due to the addition of high VA/Q regions rather than 'pure' dead space. The VA/Q distribution returned to normal within 30 minutes of stopping the He or N2 bubbles, but remained abnormal for longer periods with SF6 bubbles. The net elimination of insoluble gases (such as He or N2) was only slightly impaired by bubble emboli, provided the cardiac output remained constant. Early pulmonary edema from bubble embolization was documented by increased wet weight/dry weight ratio, but the increased lung water was not apparent on histological examination. This form of pulmonary embolus is unique in that there is a constant fraction of the vasculature blocked although any given region with embolus is undergoing continuous resportion of the bubble. This produced a partial obstruction of the affected gas exchange units which manifests as regions of high VA/Q rather than pure dead space.", "contents": "Gas exchange abnormalities produced by venous gas emboli. Bubbles of either He, N2 or SF6 were infused intravenously into anesthetized dogs at a rate of 0.2 ml/kg/min. Alterations in pulmonary gas exchange were quantitated by the invert gas elimination method during control, steady state infusion and resolution phases. The hypoxemia produced was predominantly due to regions of low VA/Q rather than pure shunt, and the increase in physiological dead space was due to the addition of high VA/Q regions rather than 'pure' dead space. The VA/Q distribution returned to normal within 30 minutes of stopping the He or N2 bubbles, but remained abnormal for longer periods with SF6 bubbles. The net elimination of insoluble gases (such as He or N2) was only slightly impaired by bubble emboli, provided the cardiac output remained constant. Early pulmonary edema from bubble embolization was documented by increased wet weight/dry weight ratio, but the increased lung water was not apparent on histological examination. This form of pulmonary embolus is unique in that there is a constant fraction of the vasculature blocked although any given region with embolus is undergoing continuous resportion of the bubble. This produced a partial obstruction of the affected gas exchange units which manifests as regions of high VA/Q rather than pure dead space."}
{"id": "PMID:217053", "title": "Characteristics of the washout dead space.", "content": "The dead space volume was reproducibly measured in normal and diseased lungs by analysis of an inert gas washout. This washout dead space was appreciably larger than that measured by the Fowler technique. In the patients, the washout dead space (VD(0)) formed 72% of the physiological dead space volume, while the Fowler (VD(F)) method accounted for only 50%. The VD(O) increased significantly with age in males, but not in females. VD(F) was not well related to age in this population. VD(O) and VD(F) did not relate to lung volume in these subjects. Although that portion of the dead space delivered in Phase I was significantly greater in males than in females, it was not responsible for the difference in dead space measured by the two techniques. This volume difference was found in that portion delivered late in the breath (Phase III). The nature of this volume is speculative, but may involve a parallel dead space that is measured in addition to the series dead space.", "contents": "Characteristics of the washout dead space. The dead space volume was reproducibly measured in normal and diseased lungs by analysis of an inert gas washout. This washout dead space was appreciably larger than that measured by the Fowler technique. In the patients, the washout dead space (VD(0)) formed 72% of the physiological dead space volume, while the Fowler (VD(F)) method accounted for only 50%. The VD(O) increased significantly with age in males, but not in females. VD(F) was not well related to age in this population. VD(O) and VD(F) did not relate to lung volume in these subjects. Although that portion of the dead space delivered in Phase I was significantly greater in males than in females, it was not responsible for the difference in dead space measured by the two techniques. This volume difference was found in that portion delivered late in the breath (Phase III). The nature of this volume is speculative, but may involve a parallel dead space that is measured in addition to the series dead space."}
{"id": "PMID:217055", "title": "[The role of vestibular and proprioceptive afferent pathways in the reaction to pushing (author's transl)].", "content": "The reaction to pushing was studied in 6 normal subjects and 3 patients with bilateral peripheral vestibular lesions. The reaction to pushing was tested on the anterior tibial and soleus, by modifying the proprioceptive afferent impulses. The respective parts of the vestibular, proprioceptive, visual components, and of a sudden, start are analyzed; the afferent impulses obtain information from the initial posture and modulate the relative importance of these different factors at a supra-segmentary level.", "contents": "[The role of vestibular and proprioceptive afferent pathways in the reaction to pushing (author's transl)]. The reaction to pushing was studied in 6 normal subjects and 3 patients with bilateral peripheral vestibular lesions. The reaction to pushing was tested on the anterior tibial and soleus, by modifying the proprioceptive afferent impulses. The respective parts of the vestibular, proprioceptive, visual components, and of a sudden, start are analyzed; the afferent impulses obtain information from the initial posture and modulate the relative importance of these different factors at a supra-segmentary level."}
{"id": "PMID:217056", "title": "[Opaque meato-cisternography in study of atypical or incomplete syndromes of cerebellopontile angle (value for diagnosis and early treatment of neurilemmoma of the 8)].", "content": "It is well-known today that there is a cisternal \"no man's land\" between the petrous bone and the cerebral trunk in which a tumour can develop insidiously. The clinical signs are very variable and often in contradiction with those described for larger tumours. Tomodensimetry is indicated, but it is not conclusive if the mass is limited to the internal auditory canal or if it extends into the angle for less than 15 mm. Opaque meato-cisternography alone, gives the following information: 1. When a pseudo-tumoural syndrome is present, the auditory canal and cisterna are well opacified. 2. If there is a tumour which extends for more than 20 mm into the cisterna, the oil has a rounded, interrupted contour, and other radiological examinations are useful in this case. 3. When the tumour extends for less than 20 mm into the angle a rounded continuous contour is seen, and Hirtz's axial incidence can be used to measure the tumour diameter. 4. Finally, when temporary opacification faults have been eliminated (after retilting), opaque meato-cisternography is the only examination able to demonstrate the early stages of a tumour, in the intra-canal stage. This early diagnostic procedure has enabled one of us to excise tumours of moderate of even very small volume, under the best surgical conditions, and with functional and vital results which we would not have obtained at a later date.", "contents": "[Opaque meato-cisternography in study of atypical or incomplete syndromes of cerebellopontile angle (value for diagnosis and early treatment of neurilemmoma of the 8)]. It is well-known today that there is a cisternal \"no man's land\" between the petrous bone and the cerebral trunk in which a tumour can develop insidiously. The clinical signs are very variable and often in contradiction with those described for larger tumours. Tomodensimetry is indicated, but it is not conclusive if the mass is limited to the internal auditory canal or if it extends into the angle for less than 15 mm. Opaque meato-cisternography alone, gives the following information: 1. When a pseudo-tumoural syndrome is present, the auditory canal and cisterna are well opacified. 2. If there is a tumour which extends for more than 20 mm into the cisterna, the oil has a rounded, interrupted contour, and other radiological examinations are useful in this case. 3. When the tumour extends for less than 20 mm into the angle a rounded continuous contour is seen, and Hirtz's axial incidence can be used to measure the tumour diameter. 4. Finally, when temporary opacification faults have been eliminated (after retilting), opaque meato-cisternography is the only examination able to demonstrate the early stages of a tumour, in the intra-canal stage. This early diagnostic procedure has enabled one of us to excise tumours of moderate of even very small volume, under the best surgical conditions, and with functional and vital results which we would not have obtained at a later date."}
{"id": "PMID:217060", "title": "[Detection of tubercular infection after BCG vaccination].", "content": "The author has followed several groups of children over a period of many years and evidenced the general decrease of the level of tuberculin reactivity. The implications are discussed, of the B.C.G. vaccination on the tuberculous allergy and the possibility to differentiate post-vaccinal allergy with the aid of skin testing, using 2 and 10 PPD units. The importance is stressed, of the vaccinal scar as an indication of a good immune reactivity, and thus of protection against contamination with virulent tuberculous baccili. The time is foreseen, when systematic vaccination with B.C.G. will reduce to such a significant degree the number of cases of tuberculosis in children that differential diagnosis on the basis of tuberculin allergy will not be necessary.", "contents": "[Detection of tubercular infection after BCG vaccination]. The author has followed several groups of children over a period of many years and evidenced the general decrease of the level of tuberculin reactivity. The implications are discussed, of the B.C.G. vaccination on the tuberculous allergy and the possibility to differentiate post-vaccinal allergy with the aid of skin testing, using 2 and 10 PPD units. The importance is stressed, of the vaccinal scar as an indication of a good immune reactivity, and thus of protection against contamination with virulent tuberculous baccili. The time is foreseen, when systematic vaccination with B.C.G. will reduce to such a significant degree the number of cases of tuberculosis in children that differential diagnosis on the basis of tuberculin allergy will not be necessary."}
{"id": "PMID:217061", "title": "[Experience gained in the Pecica region (Arad) regarding the organizational aspects of the integration of antitubercular chemotherapy in the basic health network].", "content": "The present paper reports on the author's experience concerning certain organizational aspects in the closely surveyed treatment of tuberculosis following integration of this activity in the general health network. Emphasis is layed on the role of the general practitioner and ancillary staff who must work under the guidance of a specialist in pneumophyhisiology. The importance of personal motivation in the general health services and the role of health education of the patients is underlined.", "contents": "[Experience gained in the Pecica region (Arad) regarding the organizational aspects of the integration of antitubercular chemotherapy in the basic health network]. The present paper reports on the author's experience concerning certain organizational aspects in the closely surveyed treatment of tuberculosis following integration of this activity in the general health network. Emphasis is layed on the role of the general practitioner and ancillary staff who must work under the guidance of a specialist in pneumophyhisiology. The importance of personal motivation in the general health services and the role of health education of the patients is underlined."}
{"id": "PMID:217062", "title": "[Surgical treatment of bronchial adenomas].", "content": "The authors make an analysis of the experience acquired in the Clinic of Thoracic Surgery of Bucharest, based on interventions carried out in 42 cases of bronchial adenoma hospitalized between 1962 and 1976. The fact is stressed that in none of the 42 operated patients was the carcinoid syndrome encountered with any of its specific manifestations. Also on the basis of the experience obtained the bronchologic criteria for benignity of this type of tumour (absence of the infiltration in the mucosa, surrounding the tumour) is considered as non-significant because there are frequently areas of malignant transformation inside the tumour itself, or at its lower pole that cannot be explored by bronchoscopy. Surgical treatment of bronchial adenoma included a wide range of techniques, from simple lobectomies to bronchoanastomotic interventions, and resections of the trachea. The study of postoperative results showed a good prognosis and survivals of appreciable duration only when the intervention was carried out in the I-st and the II-nd stages of the disease. This also stresses the necessity for an early diagnosis and rapid surgery in these bronchial adenomatous tumours (most of which are of the carcinoid type).", "contents": "[Surgical treatment of bronchial adenomas]. The authors make an analysis of the experience acquired in the Clinic of Thoracic Surgery of Bucharest, based on interventions carried out in 42 cases of bronchial adenoma hospitalized between 1962 and 1976. The fact is stressed that in none of the 42 operated patients was the carcinoid syndrome encountered with any of its specific manifestations. Also on the basis of the experience obtained the bronchologic criteria for benignity of this type of tumour (absence of the infiltration in the mucosa, surrounding the tumour) is considered as non-significant because there are frequently areas of malignant transformation inside the tumour itself, or at its lower pole that cannot be explored by bronchoscopy. Surgical treatment of bronchial adenoma included a wide range of techniques, from simple lobectomies to bronchoanastomotic interventions, and resections of the trachea. The study of postoperative results showed a good prognosis and survivals of appreciable duration only when the intervention was carried out in the I-st and the II-nd stages of the disease. This also stresses the necessity for an early diagnosis and rapid surgery in these bronchial adenomatous tumours (most of which are of the carcinoid type)."}
{"id": "PMID:217059", "title": "[Risk factors and high-risk groups in the prevention of tuberculosis].", "content": "Starting from the premise that in the methodology of tuberculosis control priority should be given to the higher risk groups, the authors tried to identify such groups and list them in the order of their priority within the district of a dispensary serving a population of about 400,000 inhabitants. On comparing the results of the detection of risk factors among the population in general with that per endangered groups it was found that the former presented a decrease (from 1.09 to 0.44 per thousand) and the latter an increase (from 0.91 to 1.5 per thousand). The 126 747 examinations for risk factors revealed a succesive increase in the detection indices as follows: 0.76 per thousand among students, 1.36 per thousand in silicogen risk enterprises, 2.07 per thousand among the workers on building sites, 2.22 per thousand among diabetics, 2.76 per thousand among contacts, 2.85 per thousand among hyperergic subjects, 3.89 per thousand among former patients no longer on the files, 4.17 per thousand among alcoholics and patients under psychical treatment, 6.01 per thousand among patients with minimal lesions and 6.82 thousand among those with sequelae.", "contents": "[Risk factors and high-risk groups in the prevention of tuberculosis]. Starting from the premise that in the methodology of tuberculosis control priority should be given to the higher risk groups, the authors tried to identify such groups and list them in the order of their priority within the district of a dispensary serving a population of about 400,000 inhabitants. On comparing the results of the detection of risk factors among the population in general with that per endangered groups it was found that the former presented a decrease (from 1.09 to 0.44 per thousand) and the latter an increase (from 0.91 to 1.5 per thousand). The 126 747 examinations for risk factors revealed a succesive increase in the detection indices as follows: 0.76 per thousand among students, 1.36 per thousand in silicogen risk enterprises, 2.07 per thousand among the workers on building sites, 2.22 per thousand among diabetics, 2.76 per thousand among contacts, 2.85 per thousand among hyperergic subjects, 3.89 per thousand among former patients no longer on the files, 4.17 per thousand among alcoholics and patients under psychical treatment, 6.01 per thousand among patients with minimal lesions and 6.82 thousand among those with sequelae."}
{"id": "PMID:217063", "title": "[Current incidence and clinical significance of non-culturable bacilli or those culturable with difficulty].", "content": "An analysis of 246 patients with positive smear present bacilli and negative cultures revealed that in only 9% of the cases no organized previous treatment had been applied, although almost half of these had benefited from short courses with streptomycin associated with penicillin before an exact diagnosis of tuberculosis had been made. Since the remaining 91% had had 1--2 months of chemotherapy, which frequently included rifampicin, the authors stress that microscopically detectable germs are frequently incapable to develop on culture media. These are frequently non-viable bacteria and in such conditions no subsequent modifications of the currently applied therapy scheme should be attempted. The authors show that only 26,2% of the germs from 519 positive cultures have developed after 21 days from the seeding. At 30 days the overall proportion increased to 71,2% while at 45 days 22,7% more positive cultures appeared and an additional 6,1% cultures became positive at 60 days. Tubercle bacilli become increasingly demanding and slower growing. If at 21 days only one colony was evident in 6% of the cases, while an infinite number of colonies were present in 58% of the cultures at 60 days a single colony was found in 42% of the cases, in contrast with only 9% cases with an infinite number of colonies (P less than 0,001). The delay in the growth of bacilli was parallel with the duration of chemotherapy. The results are compared with data from the literature.", "contents": "[Current incidence and clinical significance of non-culturable bacilli or those culturable with difficulty]. An analysis of 246 patients with positive smear present bacilli and negative cultures revealed that in only 9% of the cases no organized previous treatment had been applied, although almost half of these had benefited from short courses with streptomycin associated with penicillin before an exact diagnosis of tuberculosis had been made. Since the remaining 91% had had 1--2 months of chemotherapy, which frequently included rifampicin, the authors stress that microscopically detectable germs are frequently incapable to develop on culture media. These are frequently non-viable bacteria and in such conditions no subsequent modifications of the currently applied therapy scheme should be attempted. The authors show that only 26,2% of the germs from 519 positive cultures have developed after 21 days from the seeding. At 30 days the overall proportion increased to 71,2% while at 45 days 22,7% more positive cultures appeared and an additional 6,1% cultures became positive at 60 days. Tubercle bacilli become increasingly demanding and slower growing. If at 21 days only one colony was evident in 6% of the cases, while an infinite number of colonies were present in 58% of the cultures at 60 days a single colony was found in 42% of the cases, in contrast with only 9% cases with an infinite number of colonies (P less than 0,001). The delay in the growth of bacilli was parallel with the duration of chemotherapy. The results are compared with data from the literature."}
{"id": "PMID:217064", "title": "[Cerebral hemodynamic disorders in patients with chronic decompensated respiratory insufficiency. Physiopathogenetic considerations].", "content": "The present paper reports on 12 patients (8 males, 4 females) suffering from chronic decompensated respiratory failure, who presented concomitant transient haemodynamic disturbances in the carotid and vertebrobasilary systems, manifested by hemisphere or brain stem symptoms. Owing to the adaptive capacity of these patients there exists a certain tolerance threshold to hypercapnic hypoxemia, but following accentuated or rapid aggravation of acid-base hypercapnic hypoxemia, the biological balance is abruptly perturbed leading to cerebral haemodynamic disturbances. The pathophysiological mechanism of production appears to be the accumulation of acid ions caused by pH acidification of the cerebrospinal fluid. Increase in the cerebral arterial output with decrease in the rate of circulation and vascular resistance take place especially in the vessels with atheromatous or hyaline lesions. Under conditions of severe acidosic hypercapnic hypoxemia this, nevertheless, insures a minimum of 10--20% oxygen required by the metabolism of the nerve cell, sufficient for maintaining the structure of the cell (vita minima). These vasculometabolic mechanisms explain why with improvement of haematosis, following remission of the decompensated disease and fall in acidotic hypercapnic hypoxemia values, the cerebral haemodynamic disturbances also show a more or less evident remission because the nerve cells having maintained their structure are able to take up their function again.", "contents": "[Cerebral hemodynamic disorders in patients with chronic decompensated respiratory insufficiency. Physiopathogenetic considerations]. The present paper reports on 12 patients (8 males, 4 females) suffering from chronic decompensated respiratory failure, who presented concomitant transient haemodynamic disturbances in the carotid and vertebrobasilary systems, manifested by hemisphere or brain stem symptoms. Owing to the adaptive capacity of these patients there exists a certain tolerance threshold to hypercapnic hypoxemia, but following accentuated or rapid aggravation of acid-base hypercapnic hypoxemia, the biological balance is abruptly perturbed leading to cerebral haemodynamic disturbances. The pathophysiological mechanism of production appears to be the accumulation of acid ions caused by pH acidification of the cerebrospinal fluid. Increase in the cerebral arterial output with decrease in the rate of circulation and vascular resistance take place especially in the vessels with atheromatous or hyaline lesions. Under conditions of severe acidosic hypercapnic hypoxemia this, nevertheless, insures a minimum of 10--20% oxygen required by the metabolism of the nerve cell, sufficient for maintaining the structure of the cell (vita minima). These vasculometabolic mechanisms explain why with improvement of haematosis, following remission of the decompensated disease and fall in acidotic hypercapnic hypoxemia values, the cerebral haemodynamic disturbances also show a more or less evident remission because the nerve cells having maintained their structure are able to take up their function again."}
{"id": "PMID:217065", "title": "[Effectiveness of the routine treatment of workers employed in the region of the Tuberculosis center, Constan\u0163a].", "content": "The present work demonstrates the high overall efficiency of the present regimes in the treatment of tuberculosis (97%), provided the rules and indications are strictly complied with. The duration of the medical sick leave influences the regularity with which the treatment is applied. Many of the younger patients frequently accept to resume work at an earlier date. Earlier work resumption under present conditions should be had in view since it obviates the major drawbacks in the treatment of tuberculosis--socio-occupational disadaptation of the patients.", "contents": "[Effectiveness of the routine treatment of workers employed in the region of the Tuberculosis center, Constan\u0163a]. The present work demonstrates the high overall efficiency of the present regimes in the treatment of tuberculosis (97%), provided the rules and indications are strictly complied with. The duration of the medical sick leave influences the regularity with which the treatment is applied. Many of the younger patients frequently accept to resume work at an earlier date. Earlier work resumption under present conditions should be had in view since it obviates the major drawbacks in the treatment of tuberculosis--socio-occupational disadaptation of the patients."}
{"id": "PMID:217078", "title": "[Experimental neuropathy due to acrilamide. Histological and ultrastructural studies (author's transl)].", "content": "The effects of acrylamide intoxication were studied both in peripheral (PNS) and central (CNS) nervous system of rats. The animals were sacrified at different time intervals from the beginning of the intoxication. Histological and ultrastructural studies of peripheral nerves and long tracts of the spinal cord revealed a severe axonopathy, characterized by swelling of axons, particularly in the paranodal regions due to accumulation of neurofilaments with almost complete disappearance of neurotubules. There was also aggregation of dense bodies, swollen mitochondria and multivescicolar bodies in subaxolemmal regions. Presynaptic endings in the anterior horns of the spinal cord and in the cuneate nuclei were swollen and filled with packed filaments. Fiber degeneration at different stages was seen both in PNS and in CNS. These changes are not specific for acrylamide intoxication, having been observed in other experimentally induced neuropathies (n-hexane, Mn-BK, CS2, ...), as well as in a variety of diseases both genetically determined and due to exposure to toxic substances (glue-sniffing, leather cement poisoning, antiblastic therapy, ...). Accumulation of filaments in peripheral and central axons is the pattern of fiber degeneration characterizing the dying-back neuropathies. These axonal changes are particularly marked in the pacinian bodies as well as in the distal segments of the fibres. These data support the hypothesis that a dying-back neuropathy might depend on the direct effect of the toxic substance on the most vulnerable segments of the fibres, rather than on the perikaryon of the nerve cell, as previously supposed.", "contents": "[Experimental neuropathy due to acrilamide. Histological and ultrastructural studies (author's transl)]. The effects of acrylamide intoxication were studied both in peripheral (PNS) and central (CNS) nervous system of rats. The animals were sacrified at different time intervals from the beginning of the intoxication. Histological and ultrastructural studies of peripheral nerves and long tracts of the spinal cord revealed a severe axonopathy, characterized by swelling of axons, particularly in the paranodal regions due to accumulation of neurofilaments with almost complete disappearance of neurotubules. There was also aggregation of dense bodies, swollen mitochondria and multivescicolar bodies in subaxolemmal regions. Presynaptic endings in the anterior horns of the spinal cord and in the cuneate nuclei were swollen and filled with packed filaments. Fiber degeneration at different stages was seen both in PNS and in CNS. These changes are not specific for acrylamide intoxication, having been observed in other experimentally induced neuropathies (n-hexane, Mn-BK, CS2, ...), as well as in a variety of diseases both genetically determined and due to exposure to toxic substances (glue-sniffing, leather cement poisoning, antiblastic therapy, ...). Accumulation of filaments in peripheral and central axons is the pattern of fiber degeneration characterizing the dying-back neuropathies. These axonal changes are particularly marked in the pacinian bodies as well as in the distal segments of the fibres. These data support the hypothesis that a dying-back neuropathy might depend on the direct effect of the toxic substance on the most vulnerable segments of the fibres, rather than on the perikaryon of the nerve cell, as previously supposed."}
{"id": "PMID:217079", "title": "[Thorotrastoses--viewed in retrospect (author's transl)].", "content": "Thorium dioxide (Thorotrast) was used as a contrast medium from 1930 to 1945. It gave excellent contrast and was well tolerated during the application, but due to its radioactivity and its long biological half life it caused various late complications as fibrosis and malignant tumors. The late side effects of the substance are reported on, and the most frequent complication--the induction of hepatomas--is illustrated by two cases.", "contents": "[Thorotrastoses--viewed in retrospect (author's transl)]. Thorium dioxide (Thorotrast) was used as a contrast medium from 1930 to 1945. It gave excellent contrast and was well tolerated during the application, but due to its radioactivity and its long biological half life it caused various late complications as fibrosis and malignant tumors. The late side effects of the substance are reported on, and the most frequent complication--the induction of hepatomas--is illustrated by two cases."}
{"id": "PMID:217081", "title": "[Recurrent infectious parotiditis in the child (author's transl)].", "content": "On the basis of 18 cases of recurrent parotiditis in the child, the authors offer the current review of this condition: clinical features, radiological features, bacteriological features, course. They emphasize the importance of precise technique during sialography, which must include straight and lateral films. The progress of this condition is characterised by recurrences. These may be avoided by prolonged and appropriate antibiotic therapy. The improvement which takes place at puberty is of etiopathogenic significance. Bucco-dental septis, constantly present, is one of the causes favourising infectious parotiditis in child.", "contents": "[Recurrent infectious parotiditis in the child (author's transl)]. On the basis of 18 cases of recurrent parotiditis in the child, the authors offer the current review of this condition: clinical features, radiological features, bacteriological features, course. They emphasize the importance of precise technique during sialography, which must include straight and lateral films. The progress of this condition is characterised by recurrences. These may be avoided by prolonged and appropriate antibiotic therapy. The improvement which takes place at puberty is of etiopathogenic significance. Bucco-dental septis, constantly present, is one of the causes favourising infectious parotiditis in child."}
{"id": "PMID:217082", "title": "Cerebrospinal fluid content of adenylate kinase, lactate and glutathione in patients with meningitis.", "content": "Adenylate kinase activity and lactate concentration were measured in the cerebrospinal fluid (CSF) of 5 patients with bacterial meningitis, of 4 patients with probable bacterial meningitis, and of 18 patients with serous meningitis. Furthermore, for comparison measurements were also performed in CSF of 27 patients with meningism. Concomitantly glutathione was measured in CSF in most of the patients. Significantly higher values of these 3 parameters were found in the CSF of patients with bacterial and probable bacterial meningitis compared with those having serous meningitis and meningism. Adenylate kinase activity and lactate concentration in patients with serous meningitis were significantly higher than in those with meningism. All patients with a clinical diagnosis of meningitis studied so far also displayed an adenylate kinase activity in their CSF. The determination of adenylate kinase, lactate and glutathione levels in CSF might be a useful aid for the diagnosis not only of meningitis but also for the discrimination between bacterial and serous meningitis.", "contents": "Cerebrospinal fluid content of adenylate kinase, lactate and glutathione in patients with meningitis. Adenylate kinase activity and lactate concentration were measured in the cerebrospinal fluid (CSF) of 5 patients with bacterial meningitis, of 4 patients with probable bacterial meningitis, and of 18 patients with serous meningitis. Furthermore, for comparison measurements were also performed in CSF of 27 patients with meningism. Concomitantly glutathione was measured in CSF in most of the patients. Significantly higher values of these 3 parameters were found in the CSF of patients with bacterial and probable bacterial meningitis compared with those having serous meningitis and meningism. Adenylate kinase activity and lactate concentration in patients with serous meningitis were significantly higher than in those with meningism. All patients with a clinical diagnosis of meningitis studied so far also displayed an adenylate kinase activity in their CSF. The determination of adenylate kinase, lactate and glutathione levels in CSF might be a useful aid for the diagnosis not only of meningitis but also for the discrimination between bacterial and serous meningitis."}
{"id": "PMID:217083", "title": "Free plasma 11-hydroxycorticosteroids and the response to beta1-24-corticotrophin in regular haemodialysis patients.", "content": "The adrenocortical function of 59 patients on regular hemodialysis treatment was tested on 105 occasions by measuring the 30-min response of free plasma 11-hydroxycorticosteroids (11-OHCS) after intramuscular injection of 0.25 mg Synacthen (beta1-24-corticotrophin). The morning basal levels of 11-OHCS were within the normal range. The increase of 11-OHCS after injection of Synacthen was less than normal in 25% of the patients. In 9 patients with a low response an extended Synacthen test was performed. This caused a normal increase in plasma 11-OHCS but the response came later than in normal persons. After 0.25 mg Synacthen intramuscularly the 30-min response of 11-OHCS seemed to be lower on the first day than on the second day after dialysis. The present study supports the view that the pituitary-adrenocortical system is essentially intact in patients on regular hemodialysis treatment.", "contents": "Free plasma 11-hydroxycorticosteroids and the response to beta1-24-corticotrophin in regular haemodialysis patients. The adrenocortical function of 59 patients on regular hemodialysis treatment was tested on 105 occasions by measuring the 30-min response of free plasma 11-hydroxycorticosteroids (11-OHCS) after intramuscular injection of 0.25 mg Synacthen (beta1-24-corticotrophin). The morning basal levels of 11-OHCS were within the normal range. The increase of 11-OHCS after injection of Synacthen was less than normal in 25% of the patients. In 9 patients with a low response an extended Synacthen test was performed. This caused a normal increase in plasma 11-OHCS but the response came later than in normal persons. After 0.25 mg Synacthen intramuscularly the 30-min response of 11-OHCS seemed to be lower on the first day than on the second day after dialysis. The present study supports the view that the pituitary-adrenocortical system is essentially intact in patients on regular hemodialysis treatment."}
{"id": "PMID:217087", "title": "Molecular cloning of polyoma virus DNA in Escherichia coli: plasmid vector system.", "content": "A series of recombinant plasmids containing polyoma virus (PY) DNA were constructed, and their biological activity was evaluated in mice and in cultured mouse cells. While all of the recombinants studied contain the complete, potentially infectious viral DNA, in no case was the intact recombinant PY-plasmid DNA, or live Escherichia coli containing the recombinant plasmids, capable of inducing PY infection of mice, either by feeding or by parenteral injection.", "contents": "Molecular cloning of polyoma virus DNA in Escherichia coli: plasmid vector system. A series of recombinant plasmids containing polyoma virus (PY) DNA were constructed, and their biological activity was evaluated in mice and in cultured mouse cells. While all of the recombinants studied contain the complete, potentially infectious viral DNA, in no case was the intact recombinant PY-plasmid DNA, or live Escherichia coli containing the recombinant plasmids, capable of inducing PY infection of mice, either by feeding or by parenteral injection."}
{"id": "PMID:217088", "title": "Molecular cloning of polyoma virus DNA in Escherichia coli: lambda phage vector system.", "content": "The biological activity of recombinant phage and recombinant phage DNA containing monomeric or dimeric polyoma DNA inserts was examined in mice and cultured mouse cells. Recombinant preparations containing a single copy of viral DNA were invariably noninfectious; molecules containing a dimeric polyoma DNA insert were at least seven orders of magnitude less infectious than polyoma virions after parenteral inoculation. No infection was detected with any recombinant preparation after oral administration.", "contents": "Molecular cloning of polyoma virus DNA in Escherichia coli: lambda phage vector system. The biological activity of recombinant phage and recombinant phage DNA containing monomeric or dimeric polyoma DNA inserts was examined in mice and cultured mouse cells. Recombinant preparations containing a single copy of viral DNA were invariably noninfectious; molecules containing a dimeric polyoma DNA insert were at least seven orders of magnitude less infectious than polyoma virions after parenteral inoculation. No infection was detected with any recombinant preparation after oral administration."}
{"id": "PMID:217085", "title": "Neurophysiological basis of acupuncture analgesia.", "content": "This article presents a view about the neural mechanism of acupuncture analgesia and the clinical and experimental evidences on which this view is based. The analgesic effect of acupuncture is considered essentially a manifestation of the interaction of afferent impulses from the region of pain and those from the point of acupuncture. It begins with a general information leading to the development of this sensory interaction theory in interpretation of acupuncture analgesia. The nature of the acupuncture feeling, the receptors activated by acupuncture, the types of fibers involved in transmission of the afferent impulses produced by acupuncture and the processes of interaction taking place at different levels of the central nervous system are described with particular reference to the integrative action of extralemniscal system including the bulbar reticular formation and the intralaminar structures of thalamus. The possible r\u00f4le played by the putative synaptic neurotransmitters such as serotonin is only very briefly mentioned.", "contents": "Neurophysiological basis of acupuncture analgesia. This article presents a view about the neural mechanism of acupuncture analgesia and the clinical and experimental evidences on which this view is based. The analgesic effect of acupuncture is considered essentially a manifestation of the interaction of afferent impulses from the region of pain and those from the point of acupuncture. It begins with a general information leading to the development of this sensory interaction theory in interpretation of acupuncture analgesia. The nature of the acupuncture feeling, the receptors activated by acupuncture, the types of fibers involved in transmission of the afferent impulses produced by acupuncture and the processes of interaction taking place at different levels of the central nervous system are described with particular reference to the integrative action of extralemniscal system including the bulbar reticular formation and the intralaminar structures of thalamus. The possible r\u00f4le played by the putative synaptic neurotransmitters such as serotonin is only very briefly mentioned."}
{"id": "PMID:217090", "title": "[Aetiological and evolutive Particulars of parinaud's syndrome. Report of 19 cases (author's transl)].", "content": "After a summary of general specifications of Parinaud's syndrome the authors made a critical study according to 19 personal observations. They point to the aetiological interest of evolutive development of this syndrome when undergoing treatment for tumour and during the vascular malformations when fluctuations are an interesting clinical presumptive evidence.", "contents": "[Aetiological and evolutive Particulars of parinaud's syndrome. Report of 19 cases (author's transl)]. After a summary of general specifications of Parinaud's syndrome the authors made a critical study according to 19 personal observations. They point to the aetiological interest of evolutive development of this syndrome when undergoing treatment for tumour and during the vascular malformations when fluctuations are an interesting clinical presumptive evidence."}
{"id": "PMID:217089", "title": "[Granulomatous tuberculoid gastritis (author's transl)].", "content": "The authors report seven cases of tuberculoid granulomatous gastritis. Tuberculosis was the cause in three cases. Bilharziasis was the cause in two cases. Sarcoidosis was identified in one patient. In only one case was the etiology undetermined. This seems rare. Some of these form should be compared with experimental tuberculoid granulomatous gastritis, obtained after sensitisation to foreign substances included in the gastric mucosa. The organisation of the epithelioid and giant cell granuloma corresponds to an immune defence reaction of the stomach, bringing into play immunoglobulins IgG and IgM to lead to the formation of antigen antibody complexes in these tissues.", "contents": "[Granulomatous tuberculoid gastritis (author's transl)]. The authors report seven cases of tuberculoid granulomatous gastritis. Tuberculosis was the cause in three cases. Bilharziasis was the cause in two cases. Sarcoidosis was identified in one patient. In only one case was the etiology undetermined. This seems rare. Some of these form should be compared with experimental tuberculoid granulomatous gastritis, obtained after sensitisation to foreign substances included in the gastric mucosa. The organisation of the epithelioid and giant cell granuloma corresponds to an immune defence reaction of the stomach, bringing into play immunoglobulins IgG and IgM to lead to the formation of antigen antibody complexes in these tissues."}
{"id": "PMID:217091", "title": "[Antithrombin III in 86 patients with venous thrombosis (author's transl)].", "content": "Antithrombin III concentration was studied in 86 patients with recurrent or extensive venous thrombosis. Two of them were found to have an hereditary antithrombin III deficiency. 25 patients receiving heparin therapy had low antithrombin III concentration. After stopping heparin treatment antithrombin rose to a normal level. Pathological antithrombin III modifications are recalled (synthesis decrease in liver diseases, intra vascular consumption during active venous thrombosis). Antithrombin III decreased activity induced by heparin treatment is pointed out.", "contents": "[Antithrombin III in 86 patients with venous thrombosis (author's transl)]. Antithrombin III concentration was studied in 86 patients with recurrent or extensive venous thrombosis. Two of them were found to have an hereditary antithrombin III deficiency. 25 patients receiving heparin therapy had low antithrombin III concentration. After stopping heparin treatment antithrombin rose to a normal level. Pathological antithrombin III modifications are recalled (synthesis decrease in liver diseases, intra vascular consumption during active venous thrombosis). Antithrombin III decreased activity induced by heparin treatment is pointed out."}
{"id": "PMID:217093", "title": "[Use of plastic isolators in the prevention of infection in high risk patients with hematologic diseases].", "content": "The authors report a microbiological study of the flora of high risk adults with blood diseases isolated in hermetically sealed plastic isolater. This type of isolation is very effective in the prevention of infections due to hospital germs as such contamination occurred only twice in 292 days isolation and was found in only 0.8% on samples. The efficacy of methods of body decontamination and the incidence of infective complications in our series is also reported.", "contents": "[Use of plastic isolators in the prevention of infection in high risk patients with hematologic diseases]. The authors report a microbiological study of the flora of high risk adults with blood diseases isolated in hermetically sealed plastic isolater. This type of isolation is very effective in the prevention of infections due to hospital germs as such contamination occurred only twice in 292 days isolation and was found in only 0.8% on samples. The efficacy of methods of body decontamination and the incidence of infective complications in our series is also reported."}
{"id": "PMID:217095", "title": "[Long term course of insulin secretion in treated noninsulin dependent diabetics (author's transl)].", "content": "The long-term effects of sulfonamides were studied by means of hyperinsulinemia tests in 82 diabetics over a period of 12 months (24 months for 30 of them). Whereas for those obese diabetics whose only treatment was dieting--alone or combined with biguanides--hyperinsulinemia attenuates itself as do also variations in glycemia, although some asynchronism remains, in those diabetics treated with sulfonamides--alone or in combination with other treatments--the insulinemia curve is hardly modified.", "contents": "[Long term course of insulin secretion in treated noninsulin dependent diabetics (author's transl)]. The long-term effects of sulfonamides were studied by means of hyperinsulinemia tests in 82 diabetics over a period of 12 months (24 months for 30 of them). Whereas for those obese diabetics whose only treatment was dieting--alone or combined with biguanides--hyperinsulinemia attenuates itself as do also variations in glycemia, although some asynchronism remains, in those diabetics treated with sulfonamides--alone or in combination with other treatments--the insulinemia curve is hardly modified."}
{"id": "PMID:217092", "title": "[Acute poisoning. Apropos of 1200 cases].", "content": "The team studied 1 200 cases of acute intoxications both accidental and self inflicted, self inflicted poisonings are much more frequent than accidental ones and in general occur more often amongst the young and by women; the median age is about thirty. Barbituric are often the means. There is a progressive increase in the use of tranquilizers and of thymo-analeptics as their use becomes greater. A mixture of poisons increases the dangers because this frequently results in more rapid loss of consciousness; also more than one poison increases the risk of shock and of thermo-regulation, respiratory problems necessitate intubation and artificial respiration which both increase the risk of assification. The characteristics of certain poisons are stressed and in particular the thymo-analeptics; also the supervision of the patients in an intensive care unit.", "contents": "[Acute poisoning. Apropos of 1200 cases]. The team studied 1 200 cases of acute intoxications both accidental and self inflicted, self inflicted poisonings are much more frequent than accidental ones and in general occur more often amongst the young and by women; the median age is about thirty. Barbituric are often the means. There is a progressive increase in the use of tranquilizers and of thymo-analeptics as their use becomes greater. A mixture of poisons increases the dangers because this frequently results in more rapid loss of consciousness; also more than one poison increases the risk of shock and of thermo-regulation, respiratory problems necessitate intubation and artificial respiration which both increase the risk of assification. The characteristics of certain poisons are stressed and in particular the thymo-analeptics; also the supervision of the patients in an intensive care unit."}
{"id": "PMID:217096", "title": "[Hodgkin's disease. T lymphocyte defect in patients in complete remission (author's transl)].", "content": "11 patients with Hodgkin's disease in remission, including 7 patients with an initial stage III-IV, off treatment for at least 6 months, were tested for blood T lymphocyte functions. All were completely re-evaluated at the end of treatment to assess complete remission. The number of peripheral blood lymphocytes was below 1,200/cu mm 5/11 patients. Absolute numbers of E-rosette-forming T lymphocytes were decreased in 8 patients, whereas active rosettes were normal in 4/6. A slightly increased percentage of EAC rosettes, a marker for B lymphocytes, was found in only 2 patients. In vitro lymphocyte reactivity to a sub-optimal dose of PHA was studied in 9 patients. A statistically significant defect of lymphocyte transformation was observed in the patient group T lymphocytes. A membrane change is suggested rather than a true depletion. The persistance of such abnormalities long after treatment may raise the question of a complementary immunostimulating treatment in these patients.", "contents": "[Hodgkin's disease. T lymphocyte defect in patients in complete remission (author's transl)]. 11 patients with Hodgkin's disease in remission, including 7 patients with an initial stage III-IV, off treatment for at least 6 months, were tested for blood T lymphocyte functions. All were completely re-evaluated at the end of treatment to assess complete remission. The number of peripheral blood lymphocytes was below 1,200/cu mm 5/11 patients. Absolute numbers of E-rosette-forming T lymphocytes were decreased in 8 patients, whereas active rosettes were normal in 4/6. A slightly increased percentage of EAC rosettes, a marker for B lymphocytes, was found in only 2 patients. In vitro lymphocyte reactivity to a sub-optimal dose of PHA was studied in 9 patients. A statistically significant defect of lymphocyte transformation was observed in the patient group T lymphocytes. A membrane change is suggested rather than a true depletion. The persistance of such abnormalities long after treatment may raise the question of a complementary immunostimulating treatment in these patients."}
{"id": "PMID:217094", "title": "[Immunologic tests in the prognosis of solid malignant tumors].", "content": "Survival at 6, 12 and 24 months was studied in relation to the immunological findings before treatment and its variations after treatment in 600 patient and its variations after treatment in 600 patients with solid malignant tumours. Any change in any of these tests is a sign of poor prognosis proportional to the degree of this change. The most precise prognosis is given by an association of these tests. These two year survival rate for tumours without apparent spread was 87% if the tests were normal, 43% if one group of tests was disturbed and 11% if two groups of tests were abnormal. With local or regional spread, the survival was 52% in cases with normal tests, 12% if one group was disturbed, and 4% if both groups of tests were abnormal. With multiple metastases, the survival rates were respectively 24%, 4% and 0%. Thus the prognosis is less unfavourable for a tumour with general spread and normal immunological tests (24%) than for a localised tumour with a disturbance of two groups of immunological tests (11%). These immunological tests carried out before any treatment are thus very valuable in prognosis, independant of the apparent extension of the tumour. This indications are important in deciding on treatment.", "contents": "[Immunologic tests in the prognosis of solid malignant tumors]. Survival at 6, 12 and 24 months was studied in relation to the immunological findings before treatment and its variations after treatment in 600 patient and its variations after treatment in 600 patients with solid malignant tumours. Any change in any of these tests is a sign of poor prognosis proportional to the degree of this change. The most precise prognosis is given by an association of these tests. These two year survival rate for tumours without apparent spread was 87% if the tests were normal, 43% if one group of tests was disturbed and 11% if two groups of tests were abnormal. With local or regional spread, the survival was 52% in cases with normal tests, 12% if one group was disturbed, and 4% if both groups of tests were abnormal. With multiple metastases, the survival rates were respectively 24%, 4% and 0%. Thus the prognosis is less unfavourable for a tumour with general spread and normal immunological tests (24%) than for a localised tumour with a disturbance of two groups of immunological tests (11%). These immunological tests carried out before any treatment are thus very valuable in prognosis, independant of the apparent extension of the tumour. This indications are important in deciding on treatment."}
{"id": "PMID:217097", "title": "[Minimal brain dysfunction. Our investigation of choreiform syndrome in children with MBD (author's transl)].", "content": "It is the purpose of this communication to study statistical correlations between the different symptomes of MBD ; speech defect, dyslexia, hyperactivity, poor muscular control, give a school handicap for about 10 per cent of children, excluding cerebral palsy, sensorial trouble, or intellectual defect. The choreiforme syndrome is a systematic investigation in a group of 60 children selected with two symptomes of MBD. Choreiform movements are found in 48 per cent of our MBD patients (40 per cent of patients with hyperactivity and 50 per cent of patients with serious dyslexia).", "contents": "[Minimal brain dysfunction. Our investigation of choreiform syndrome in children with MBD (author's transl)]. It is the purpose of this communication to study statistical correlations between the different symptomes of MBD ; speech defect, dyslexia, hyperactivity, poor muscular control, give a school handicap for about 10 per cent of children, excluding cerebral palsy, sensorial trouble, or intellectual defect. The choreiforme syndrome is a systematic investigation in a group of 60 children selected with two symptomes of MBD. Choreiform movements are found in 48 per cent of our MBD patients (40 per cent of patients with hyperactivity and 50 per cent of patients with serious dyslexia)."}
{"id": "PMID:217099", "title": "[Long term psychiatric treatment and surgical operations].", "content": "Frequently, long term psychiatric treatments are interrupted unfortunately. Although sometimes this interruption is necessary owing to the danger of an anaesthetic, particularly in the case of IMAO, this interruption should be only provisional or else a relapse will occur a few weeks later. It is always advisable to take the advice of a psychiatrist before interrupting the treatment.", "contents": "[Long term psychiatric treatment and surgical operations]. Frequently, long term psychiatric treatments are interrupted unfortunately. Although sometimes this interruption is necessary owing to the danger of an anaesthetic, particularly in the case of IMAO, this interruption should be only provisional or else a relapse will occur a few weeks later. It is always advisable to take the advice of a psychiatrist before interrupting the treatment."}
{"id": "PMID:217098", "title": "[Salt-free diet and diuretics in the elderly (author's transl)].", "content": "A salt-free diet is usually useless or dangerous in the elderly subject. It has at present only rare indications, such as after acute pulmonary oedema or congestive heart failure during initial treatment. In all other cases, it may be replaced by a reasonable diet; sodium intake remains permitted, but naturally one should not fall in the opposite extreme. As in younger subjects, and provided one takes into consideration the subjacent renal condition, properly prescribed diuretics have transformed the situation in the treatment of heart failure as in essential hypertension. Naturally the patient still requires regular clinical supervision and laboratory tests which may in practice be limited to periodical estimation of blood urea and serum potassium, less regularly, blood sugar and uric acid.", "contents": "[Salt-free diet and diuretics in the elderly (author's transl)]. A salt-free diet is usually useless or dangerous in the elderly subject. It has at present only rare indications, such as after acute pulmonary oedema or congestive heart failure during initial treatment. In all other cases, it may be replaced by a reasonable diet; sodium intake remains permitted, but naturally one should not fall in the opposite extreme. As in younger subjects, and provided one takes into consideration the subjacent renal condition, properly prescribed diuretics have transformed the situation in the treatment of heart failure as in essential hypertension. Naturally the patient still requires regular clinical supervision and laboratory tests which may in practice be limited to periodical estimation of blood urea and serum potassium, less regularly, blood sugar and uric acid."}
{"id": "PMID:217106", "title": "Therapeutic abortion on psychiatric grounds. Part II. The continuing debate.", "content": "Over the past few decades, attitudes towards therapeutic abortion have gradually changed in many countries from denial and punishment to acceptance. The debate on this emotionally laden subject still continues. In this article, we review some of the recent literature covering therapeutic abortion on psychiatric grounds, including studies of women granted termination as well as those refused. Other related areas, such as the long-term effect on children born after the refusal of termination and the relevance of this to preventative psychiatry, are also considered.", "contents": "Therapeutic abortion on psychiatric grounds. Part II. The continuing debate. Over the past few decades, attitudes towards therapeutic abortion have gradually changed in many countries from denial and punishment to acceptance. The debate on this emotionally laden subject still continues. In this article, we review some of the recent literature covering therapeutic abortion on psychiatric grounds, including studies of women granted termination as well as those refused. Other related areas, such as the long-term effect on children born after the refusal of termination and the relevance of this to preventative psychiatry, are also considered."}
{"id": "PMID:217102", "title": "[The effect of vincamine on vigilance disorders in the elderly (author's transl)].", "content": "The vigilance is, now, recognised as an active phenomenon submitted to definite structures, separate from those supervising sleep. A good cerebral function is required for vigilance maintenance and it is easily understood that cerebral alterations in aging result in vigilance decrease. The eminent repercussion of these disorders on the behavioral adaptation of the aged justified an awaking therapy. This original characteristic of vincamine, and specially of Pervincamine Forte Retard, is a fundamental discovery in cognitive functions maintenance of the aged people.", "contents": "[The effect of vincamine on vigilance disorders in the elderly (author's transl)]. The vigilance is, now, recognised as an active phenomenon submitted to definite structures, separate from those supervising sleep. A good cerebral function is required for vigilance maintenance and it is easily understood that cerebral alterations in aging result in vigilance decrease. The eminent repercussion of these disorders on the behavioral adaptation of the aged justified an awaking therapy. This original characteristic of vincamine, and specially of Pervincamine Forte Retard, is a fundamental discovery in cognitive functions maintenance of the aged people."}
{"id": "PMID:217108", "title": "High-density lipoproteins in the prevention of atherosclerotic heart disease. Part I. Epidemiological and family studies.", "content": "It has recently been proposed that the concentration of the high-density lipoprotein (HDL) fraction in plasma bears a negative relationship to the incidence of atherosclerotic heart disease. The biological and environmental factors affecting plasma HDL levels and the evidence pertaining to the proposed 'negative risk potential' of this lipoprotein are reviewed. HDL concentrations are low at birth, but rise rapidly in early infancy to adult or above-normal adult levels. This trend is influenced by biological factors such as sex and ethnicity and by a host of environmental variables. Despite methodological inadequacies in some studies, the epidemiological evidence consistently reflects an inverse relationship between the level of HDL in the plasma and the risk of ischaemic heart disease. Investigations on families suffering from genetic dyslipoproteinaemias, characterized by reduced levels of low-density lipoprotein (LDL) relative to HDL, suggest that the LDL:HDL ratio is itself an important determinant of atherosclerotic heart disease. The practical application of this information is limited by the lack of reliable reference ranges in various population groups and the absence of quantitative data regarding the 'negative risk potential' of any given concentration of plasma HDL in the presence of other positive and negative risk factors.", "contents": "High-density lipoproteins in the prevention of atherosclerotic heart disease. Part I. Epidemiological and family studies. It has recently been proposed that the concentration of the high-density lipoprotein (HDL) fraction in plasma bears a negative relationship to the incidence of atherosclerotic heart disease. The biological and environmental factors affecting plasma HDL levels and the evidence pertaining to the proposed 'negative risk potential' of this lipoprotein are reviewed. HDL concentrations are low at birth, but rise rapidly in early infancy to adult or above-normal adult levels. This trend is influenced by biological factors such as sex and ethnicity and by a host of environmental variables. Despite methodological inadequacies in some studies, the epidemiological evidence consistently reflects an inverse relationship between the level of HDL in the plasma and the risk of ischaemic heart disease. Investigations on families suffering from genetic dyslipoproteinaemias, characterized by reduced levels of low-density lipoprotein (LDL) relative to HDL, suggest that the LDL:HDL ratio is itself an important determinant of atherosclerotic heart disease. The practical application of this information is limited by the lack of reliable reference ranges in various population groups and the absence of quantitative data regarding the 'negative risk potential' of any given concentration of plasma HDL in the presence of other positive and negative risk factors."}
{"id": "PMID:217101", "title": "[A study on the use of ginkor in proctology (author's transl)].", "content": "A total of 37 ambulatory patients with proctological conditions were treated with Ginkor as preparatory therapy before instrumental treatment (sclerosants or elastic ligatures). Greater importance was attached to its hemostatic activity; always objective though sometimes transitory, than to the improvement in various painful functional syndromes. Changes in hemorrhoidal morphology were not included in the assessment, as they demonstrate very little in the course of general treatment, except in bouts of acute inflammation and more particularly when oedema and thrombis occur. After treatment, the functional syndrome (heaviness, tenesmus) which was present in 29 patients was absent in 9 cases, reduced in 13, and unchanged in 7. Pruritus ani, which was present in 14 patients, was absent in 4 cases, reduced in 5, unchanged in 4, and impossible to evaluate in 1 case. Rectorrhagia disappeared in 12 out of 20 cases, was reduced in 4 cases, and persisted in 4 others. Overall, there were 12 very satisfactory results, 13 incomplete results, 3 moderate results, and 9 cases where no effect was noted.", "contents": "[A study on the use of ginkor in proctology (author's transl)]. A total of 37 ambulatory patients with proctological conditions were treated with Ginkor as preparatory therapy before instrumental treatment (sclerosants or elastic ligatures). Greater importance was attached to its hemostatic activity; always objective though sometimes transitory, than to the improvement in various painful functional syndromes. Changes in hemorrhoidal morphology were not included in the assessment, as they demonstrate very little in the course of general treatment, except in bouts of acute inflammation and more particularly when oedema and thrombis occur. After treatment, the functional syndrome (heaviness, tenesmus) which was present in 29 patients was absent in 9 cases, reduced in 13, and unchanged in 7. Pruritus ani, which was present in 14 patients, was absent in 4 cases, reduced in 5, unchanged in 4, and impossible to evaluate in 1 case. Rectorrhagia disappeared in 12 out of 20 cases, was reduced in 4 cases, and persisted in 4 others. Overall, there were 12 very satisfactory results, 13 incomplete results, 3 moderate results, and 9 cases where no effect was noted."}
{"id": "PMID:217109", "title": "High-density lipoproteins in the prevention of atherosclerotic heart disease. Part II. Biochemical role in the pathogenesis of atherosclerosis.", "content": "Evidence is presented that high-density lipoprotein (HDL) promotes the efflux of cholesterol from cells in vitro, and may thus play an important role in the transport of cholesterol from non-hepatic tissues to the liver for excretion. Hypothetical schemes are presented whereby this may be achieved in vivo. This putative function of HDL may be of particular importance in situations in which the capacity of cells to limit the uptake of cholesterol is exceeded, and may therefore constitute the basis for the proposed antiatherogenic action of plasma HDL. However, direct data on the transport function of HDL in intact organisms are meagre. Furthermore, a characteristic of mature atherosclerotic lesions is the extracellular, rather than the intracellular, deposition of cholesterol and other lipids, and the degree to which HDL may influence this process has not been demonstrated. Finally, in inherited disorders which markedly impair the putative HDL transport pathway, atherosclerotic heart disease is generally not an early or severe complication. Despite these caveats, the physiological significance of HDL deserves further attention in order to clarify the uncertainties enumerated above. The clinical application of plasma HDL assay is limited at present to excluding the clinically non-deleterious condition of hyperalpha (HDL)-lipoproteinaemia in patients suffering from familial hypercholesterolaemia.", "contents": "High-density lipoproteins in the prevention of atherosclerotic heart disease. Part II. Biochemical role in the pathogenesis of atherosclerosis. Evidence is presented that high-density lipoprotein (HDL) promotes the efflux of cholesterol from cells in vitro, and may thus play an important role in the transport of cholesterol from non-hepatic tissues to the liver for excretion. Hypothetical schemes are presented whereby this may be achieved in vivo. This putative function of HDL may be of particular importance in situations in which the capacity of cells to limit the uptake of cholesterol is exceeded, and may therefore constitute the basis for the proposed antiatherogenic action of plasma HDL. However, direct data on the transport function of HDL in intact organisms are meagre. Furthermore, a characteristic of mature atherosclerotic lesions is the extracellular, rather than the intracellular, deposition of cholesterol and other lipids, and the degree to which HDL may influence this process has not been demonstrated. Finally, in inherited disorders which markedly impair the putative HDL transport pathway, atherosclerotic heart disease is generally not an early or severe complication. Despite these caveats, the physiological significance of HDL deserves further attention in order to clarify the uncertainties enumerated above. The clinical application of plasma HDL assay is limited at present to excluding the clinically non-deleterious condition of hyperalpha (HDL)-lipoproteinaemia in patients suffering from familial hypercholesterolaemia."}
{"id": "PMID:217113", "title": "Genetic and biochemical studies with the adenosine analogs toyocamycin and tubercidin: mutation at the adenosine kinase locus in Chinese hamster cells.", "content": "The pyrrolopyrimidine nucleosides toyocamycin and tubercidin show several unique features of growth inhibition in Chinese hamster ovary (CHO) cells. Stable mutants which are more than 600-fold resistant to these drugs are obtained in CHO cells at a strikingly high frequency of approximately 10(-3), in the absence of mutagenesis. The mutants resistant to toyocamycin (Toyr) and tubercidin (Tubr) exhibit similar cross-resistance patterns to the two selective drugs as well as to adenosine and 6-methyl mercaptopurine riboside, indicating that the same lesion is probably involved in all cases. The mutants examined were found to be deficient in the enzyme adenosine kinase (AK), indicating that the phosphorylation of these analogs is an essential first step in their toxic action. The above mutants (AK-) behaved recessively in cell hybrids, and segregation studies indicate that the AK locus is not linked to the X chromosome. The frequencies of similar Toyr mutants in other Chinese hamster lines, e.g., V79, CHW, M3-1, GM7, and CHO-K1, varied from similar to more than three logs less than that observed for CHO cells, indicating that various cell lines probably differ in the number of functional gene copies for this locus.", "contents": "Genetic and biochemical studies with the adenosine analogs toyocamycin and tubercidin: mutation at the adenosine kinase locus in Chinese hamster cells. The pyrrolopyrimidine nucleosides toyocamycin and tubercidin show several unique features of growth inhibition in Chinese hamster ovary (CHO) cells. Stable mutants which are more than 600-fold resistant to these drugs are obtained in CHO cells at a strikingly high frequency of approximately 10(-3), in the absence of mutagenesis. The mutants resistant to toyocamycin (Toyr) and tubercidin (Tubr) exhibit similar cross-resistance patterns to the two selective drugs as well as to adenosine and 6-methyl mercaptopurine riboside, indicating that the same lesion is probably involved in all cases. The mutants examined were found to be deficient in the enzyme adenosine kinase (AK), indicating that the phosphorylation of these analogs is an essential first step in their toxic action. The above mutants (AK-) behaved recessively in cell hybrids, and segregation studies indicate that the AK locus is not linked to the X chromosome. The frequencies of similar Toyr mutants in other Chinese hamster lines, e.g., V79, CHW, M3-1, GM7, and CHO-K1, varied from similar to more than three logs less than that observed for CHO cells, indicating that various cell lines probably differ in the number of functional gene copies for this locus."}
{"id": "PMID:217114", "title": "Morphologic and clinical aspects of estrogen receptors in carcinoma of the breast.", "content": "Morphological and cytologic features and preliminary survival data were correlated with the presence or absence of estrogen receptor protein in tissues from 123 primary and 26 metastatic carcinomas of the breast. The estrogen receptor positive tumors were somewhat smaller, 2.8 centimeters in diameter, than the estrogen receptor negative tumors, 3.2 centimeters, but the rate of axillary lymph node metastasis was similar. Fifty-eight per cent of the infiltrating ductal carcinomas, 64 per cent of 11 infiltrating lobular carcinomas and all eight less common cell types including: four mucinous; two papillary; one adenoid cystic, and one tubular carcinoma were estrogen receptor positive. Twenty-one of 33 aspiration smears performed were cytologically positive, the remaining 12 suspected of being carcinoma. Eleven of the 13 estrogen receptor negative tumors that were aspirated were positive possibly due to a lesser differentiation. Sixty per cent of the patients who nine to 40 months after operation are living without known recurrent disease had estrogen receptor positive tumors, but only 28 per cent of the 18 patients who have died of carcinoma of the breast or are living with known recurrent disease were in this category, suggesting that, in spite of a similar rate of axillary lymph node metastasis and without regard to the modality of treatment, estrogen receptor negative tumors tend to have a less favorable course.", "contents": "Morphologic and clinical aspects of estrogen receptors in carcinoma of the breast. Morphological and cytologic features and preliminary survival data were correlated with the presence or absence of estrogen receptor protein in tissues from 123 primary and 26 metastatic carcinomas of the breast. The estrogen receptor positive tumors were somewhat smaller, 2.8 centimeters in diameter, than the estrogen receptor negative tumors, 3.2 centimeters, but the rate of axillary lymph node metastasis was similar. Fifty-eight per cent of the infiltrating ductal carcinomas, 64 per cent of 11 infiltrating lobular carcinomas and all eight less common cell types including: four mucinous; two papillary; one adenoid cystic, and one tubular carcinoma were estrogen receptor positive. Twenty-one of 33 aspiration smears performed were cytologically positive, the remaining 12 suspected of being carcinoma. Eleven of the 13 estrogen receptor negative tumors that were aspirated were positive possibly due to a lesser differentiation. Sixty per cent of the patients who nine to 40 months after operation are living without known recurrent disease had estrogen receptor positive tumors, but only 28 per cent of the 18 patients who have died of carcinoma of the breast or are living with known recurrent disease were in this category, suggesting that, in spite of a similar rate of axillary lymph node metastasis and without regard to the modality of treatment, estrogen receptor negative tumors tend to have a less favorable course."}
{"id": "PMID:217110", "title": "High rates of enteric protozoal infections in selected homosexual men attending a venereal disease clinic.", "content": "Stool specimens from 89 high-risk, sexually active homosexual men were screened for enteric protozoal cysts. Patients whose specimens contained nonpathogenic cysts were investigated further by examination of fresh purged specimens. A total of 27 of the initial specimens (30%) contained protozoal cysts. Twenty-three patients (26%) harbored pathogens. There were 18 cases (20%) of amebiasis and 11 cases (12%) of giardiasis. Six men (7%) had concurrent amebiasis and giardiasis. The presence of infections correlated with a history of anilingus but not with place of birth, travel, or history of symptoms. The exceptionally high rate of prevalence of intestinal protozoal infection in this population suggests that enteric protozoal infections are important among sexually transmitted diseases.", "contents": "High rates of enteric protozoal infections in selected homosexual men attending a venereal disease clinic. Stool specimens from 89 high-risk, sexually active homosexual men were screened for enteric protozoal cysts. Patients whose specimens contained nonpathogenic cysts were investigated further by examination of fresh purged specimens. A total of 27 of the initial specimens (30%) contained protozoal cysts. Twenty-three patients (26%) harbored pathogens. There were 18 cases (20%) of amebiasis and 11 cases (12%) of giardiasis. Six men (7%) had concurrent amebiasis and giardiasis. The presence of infections correlated with a history of anilingus but not with place of birth, travel, or history of symptoms. The exceptionally high rate of prevalence of intestinal protozoal infection in this population suggests that enteric protozoal infections are important among sexually transmitted diseases."}
{"id": "PMID:217115", "title": "Epidemiology of breast carcinoma: Age, menstrual status, and exogenous hormone usage in patients with lobular carcinoma in situ.", "content": "Lobular carcinoma in situ (LCIS) of the breast is a neoplastic condition associated with premenopausal women and it is largely for this reason that LCIS has been considered to be an estrogen-dependent lesion. In this report we present the results of a study of age at diagnosis, menstrual status, and exogenous hormone usage in 59 women with LCIS and in 190 patients with duct carcinoma. When LCIS was associated with duct carcinoma, 46% of patients were postmenopausal and in the group that also had infiltrating lobular carcinoma 71% were postmenopausal. Nine of 39 (23%) patients whose only carcinoma was LCIS were postmenopausal, 56% were premenopausal and 21% were menopausal. Seven of the nine postmenopausal women had never used a hormone-containing medication. In a comparison group with only duct carcinoma, 59.4% were postmenopausal and 35.2% had taken a hormone preparation. The high proportion of postmenopausal patients with LCIS leaves considerable doubt as to whether all lesions termed LCIS are equally dependent on estrogens at all stages in their evolution. We found no evidence to link LCIS with exogenous hormone usage in postmenopausal women. Prospective studies of hormone levels in patients with LCIS and in their relatives may provide an explanation for persistence of the lesion in postmenopausal women and could aid in identifying women at risk of developing invasive carcinoma.", "contents": "Epidemiology of breast carcinoma: Age, menstrual status, and exogenous hormone usage in patients with lobular carcinoma in situ. Lobular carcinoma in situ (LCIS) of the breast is a neoplastic condition associated with premenopausal women and it is largely for this reason that LCIS has been considered to be an estrogen-dependent lesion. In this report we present the results of a study of age at diagnosis, menstrual status, and exogenous hormone usage in 59 women with LCIS and in 190 patients with duct carcinoma. When LCIS was associated with duct carcinoma, 46% of patients were postmenopausal and in the group that also had infiltrating lobular carcinoma 71% were postmenopausal. Nine of 39 (23%) patients whose only carcinoma was LCIS were postmenopausal, 56% were premenopausal and 21% were menopausal. Seven of the nine postmenopausal women had never used a hormone-containing medication. In a comparison group with only duct carcinoma, 59.4% were postmenopausal and 35.2% had taken a hormone preparation. The high proportion of postmenopausal patients with LCIS leaves considerable doubt as to whether all lesions termed LCIS are equally dependent on estrogens at all stages in their evolution. We found no evidence to link LCIS with exogenous hormone usage in postmenopausal women. Prospective studies of hormone levels in patients with LCIS and in their relatives may provide an explanation for persistence of the lesion in postmenopausal women and could aid in identifying women at risk of developing invasive carcinoma."}
{"id": "PMID:217125", "title": "The control of lymphoid leukosis in a flock White Plymouth Rock chickens.", "content": "Lymphoid leukosis (LL) was successfully controlled in a commercial basic breeding line of White Plymouth Rock chickens. The control method has been developed for breeder flocks and consists of three elements: --In the flock under study, homogenates of embryos from all eggs collected during a number of 14-day periods are tested for the presence of LL viruses. --Only eggs from hens that have been shown not to shed virus in their eggs are used for the production of progeny. The offspring are reared in isolation during the first two months of life, at which time the age-related resistance against tumour formation by LL viruses appears to be sufficiently developed. --The chickens are subsequently inoculated intramuscularly with LL viruses of subgroups A and B transferred to a conventional chicken house. The vaccination raises a solid immunity to horizontal LL virus exposure and, due to the age-related resistance, tumour formation does not follow. No excretion of LL viruses could be detected in three generations of White Plymouth Rock chickens to which the three elements of the control procedure were applied. Clinical disease was not observed in any of the chickens under notice.", "contents": "The control of lymphoid leukosis in a flock White Plymouth Rock chickens. Lymphoid leukosis (LL) was successfully controlled in a commercial basic breeding line of White Plymouth Rock chickens. The control method has been developed for breeder flocks and consists of three elements: --In the flock under study, homogenates of embryos from all eggs collected during a number of 14-day periods are tested for the presence of LL viruses. --Only eggs from hens that have been shown not to shed virus in their eggs are used for the production of progeny. The offspring are reared in isolation during the first two months of life, at which time the age-related resistance against tumour formation by LL viruses appears to be sufficiently developed. --The chickens are subsequently inoculated intramuscularly with LL viruses of subgroups A and B transferred to a conventional chicken house. The vaccination raises a solid immunity to horizontal LL virus exposure and, due to the age-related resistance, tumour formation does not follow. No excretion of LL viruses could be detected in three generations of White Plymouth Rock chickens to which the three elements of the control procedure were applied. Clinical disease was not observed in any of the chickens under notice."}
{"id": "PMID:217126", "title": "ELISA for the serology of FIP virus.", "content": "An enzyme linked immunosorbent assay (ELISA) for feline infectious peritonitis (FIP) virus serology is described. The assay is analogous to a previously developed indirect heterologous immunofluorescence test (IFT) in which transmissible gastroenteritis (TGE) viral antigen was used. Comparative testing of selected feline sera in both assays resulted in corresponding titers, which justifies the conclusion that the ELISA is a reliable test for the serology of FIP virus.", "contents": "ELISA for the serology of FIP virus. An enzyme linked immunosorbent assay (ELISA) for feline infectious peritonitis (FIP) virus serology is described. The assay is analogous to a previously developed indirect heterologous immunofluorescence test (IFT) in which transmissible gastroenteritis (TGE) viral antigen was used. Comparative testing of selected feline sera in both assays resulted in corresponding titers, which justifies the conclusion that the ELISA is a reliable test for the serology of FIP virus."}
{"id": "PMID:217127", "title": "[Carcinogenic effect, on the liver, of an insecticide: aramite (author's transl)].", "content": "Aramite has been administered to male rats by oral route during 56 weeks at a daily dose of 400 mg/kg. There was a decrease of the body weight and several animals died. Liver hypertrophy was observed with neoplasic proliferation of parenchymatous cells and cholangiocarcinoma.", "contents": "[Carcinogenic effect, on the liver, of an insecticide: aramite (author's transl)]. Aramite has been administered to male rats by oral route during 56 weeks at a daily dose of 400 mg/kg. There was a decrease of the body weight and several animals died. Liver hypertrophy was observed with neoplasic proliferation of parenchymatous cells and cholangiocarcinoma."}
{"id": "PMID:217131", "title": "Where are they now? A follow-up study of suicide attempters from the Golden Gate Bridge.", "content": "The Golden Gate Bridge is currently the number one suicide location in the world. From the opening day, May 18, 1937 to April 1, 1978, there have been 625 officially reported suicide deaths and perhaps more than 200 others which have gone unseen and unreported. Proposals for the construction of a hardware antisuicide barrier have been challenged with the untested contention that \"they'll just go someplace else.\" This research tests the contention by describing and evaluating the long-term mortality experience of the 515 persons who had attempted suicide from the Golden Gate Bridge but were restrained, from the opening day through the year 1971 plus a comparison group of 184 persons who made nonbridge suicide attempts during 1956--57 and were treated at the emergency room of a large metropolitan hospital and were also followed through the close of 1971. Results of the followup study are directed toward answering the important question: \"Will a person who is prevented from suicide in one location inexorably tend to attempt and commit suicide elsewhere?\"", "contents": "Where are they now? A follow-up study of suicide attempters from the Golden Gate Bridge. The Golden Gate Bridge is currently the number one suicide location in the world. From the opening day, May 18, 1937 to April 1, 1978, there have been 625 officially reported suicide deaths and perhaps more than 200 others which have gone unseen and unreported. Proposals for the construction of a hardware antisuicide barrier have been challenged with the untested contention that \"they'll just go someplace else.\" This research tests the contention by describing and evaluating the long-term mortality experience of the 515 persons who had attempted suicide from the Golden Gate Bridge but were restrained, from the opening day through the year 1971 plus a comparison group of 184 persons who made nonbridge suicide attempts during 1956--57 and were treated at the emergency room of a large metropolitan hospital and were also followed through the close of 1971. Results of the followup study are directed toward answering the important question: \"Will a person who is prevented from suicide in one location inexorably tend to attempt and commit suicide elsewhere?\""}
{"id": "PMID:217133", "title": "Effect of cyclic AMP on transformation and proliferation of leishmania cells.", "content": "A correlation between cyclic AMP (adenosine 3' : 5'-monophosphate) concentration within Leishmania cells and proliferation and transformation is demonstrated. By addition of dibutyryl cyclic AMP and cyclic AMP-phosphodiesterase inhibitors to the culture medium the intracellular level of cyclic AMP was increased. In the presence of 1mM caffeine the level of cyclic AMP accumulated in L. tropica promastigotes from 90 pmoles up to 380 pmoles per 10(9) cells, whereas the proliferation rate decreased to 50%. In the case of L. donovani the transformation of amastigotes to promastigotes was inhibited by addition of dibutyryl cyclic AMP as well as caffeine and papaverine. Especially caffeine (2mM) and papaverine (0.1mM) reduced the transformation rate to less than 5% after 48 h, compared to 35% of the control.", "contents": "Effect of cyclic AMP on transformation and proliferation of leishmania cells. A correlation between cyclic AMP (adenosine 3' : 5'-monophosphate) concentration within Leishmania cells and proliferation and transformation is demonstrated. By addition of dibutyryl cyclic AMP and cyclic AMP-phosphodiesterase inhibitors to the culture medium the intracellular level of cyclic AMP was increased. In the presence of 1mM caffeine the level of cyclic AMP accumulated in L. tropica promastigotes from 90 pmoles up to 380 pmoles per 10(9) cells, whereas the proliferation rate decreased to 50%. In the case of L. donovani the transformation of amastigotes to promastigotes was inhibited by addition of dibutyryl cyclic AMP as well as caffeine and papaverine. Especially caffeine (2mM) and papaverine (0.1mM) reduced the transformation rate to less than 5% after 48 h, compared to 35% of the control."}
{"id": "PMID:217136", "title": "Isolation of CEA-like material from urinary bladder carcinoma.", "content": "Carcinoembryonic antigen (CEA)-like material from urinary bladder carcinoma was purified and compared with the immunological and physico-chemical properties of CEA isolated from colon cancer. After immunoadsorbent purification, the final step in a purification procedure similar to that adopted for colon cancer CEA, two main molecular species were identified: 1) Material identical with colon cancer CEA with respect to molecular size, PCA solubility, ability to bind to Con A, and most important the ability to bind to specific monkey anti-CEA serum. 2) Material with the same chromatographic and immunological properties as NCA.", "contents": "Isolation of CEA-like material from urinary bladder carcinoma. Carcinoembryonic antigen (CEA)-like material from urinary bladder carcinoma was purified and compared with the immunological and physico-chemical properties of CEA isolated from colon cancer. After immunoadsorbent purification, the final step in a purification procedure similar to that adopted for colon cancer CEA, two main molecular species were identified: 1) Material identical with colon cancer CEA with respect to molecular size, PCA solubility, ability to bind to Con A, and most important the ability to bind to specific monkey anti-CEA serum. 2) Material with the same chromatographic and immunological properties as NCA."}
{"id": "PMID:217137", "title": "Adrenal cortical tumors in children.", "content": "A review of the literature reveals 230 cases of adrenal cortical tumors in children. We add an additional 7 cases. Signs, symptoms, laboratory studies, and treatment of this rare rate tumor are discussed.", "contents": "Adrenal cortical tumors in children. A review of the literature reveals 230 cases of adrenal cortical tumors in children. We add an additional 7 cases. Signs, symptoms, laboratory studies, and treatment of this rare rate tumor are discussed."}
{"id": "PMID:217134", "title": "Histopathology and epidemiology of breast cancer in the Padua area.", "content": "The histologic epidemiology of all breast cancer cases that had been diagnosed in the Padua area over an 11-year period was studied, and the absolute and relative distribution of breast cancer, location indices according to histologic types, 5-yr distribution and annual age-specific incidences of infiltrating and noninfiltrating cancers, as well as noncancerous disease were calculated. The results suggest that the Padua area should be considered a medium-high risk area along with England and Scandinavia.", "contents": "Histopathology and epidemiology of breast cancer in the Padua area. The histologic epidemiology of all breast cancer cases that had been diagnosed in the Padua area over an 11-year period was studied, and the absolute and relative distribution of breast cancer, location indices according to histologic types, 5-yr distribution and annual age-specific incidences of infiltrating and noninfiltrating cancers, as well as noncancerous disease were calculated. The results suggest that the Padua area should be considered a medium-high risk area along with England and Scandinavia."}
{"id": "PMID:217140", "title": "Observations on outbreaks of respiratory disease in housed calves--(2) Pathological and microbiological findings.", "content": "Extensive pneumonic lesions were present in 42 out of 43 calves obtained for post mortem examination from 34 outbreaks of respiratory disease in Northern Ireland. Bronchiolitis and alveolitis with necrosis of bronchiolar mucosa which progressed to bronchiolitis obliterans and peribronchiolar fibrosis were prominent histopathological features in the lungs of calves obtained live. The majority of calves which died within the first two months of these outbreaks had severe exudative bronchopneumonia with marked vascular damage and necrosis of pulmonary parenchyma. Pasteurella spp, Mycoplasma spp and P13 virus were the organisms most frequently recovered from the pneumonic lungs.", "contents": "Observations on outbreaks of respiratory disease in housed calves--(2) Pathological and microbiological findings. Extensive pneumonic lesions were present in 42 out of 43 calves obtained for post mortem examination from 34 outbreaks of respiratory disease in Northern Ireland. Bronchiolitis and alveolitis with necrosis of bronchiolar mucosa which progressed to bronchiolitis obliterans and peribronchiolar fibrosis were prominent histopathological features in the lungs of calves obtained live. The majority of calves which died within the first two months of these outbreaks had severe exudative bronchopneumonia with marked vascular damage and necrosis of pulmonary parenchyma. Pasteurella spp, Mycoplasma spp and P13 virus were the organisms most frequently recovered from the pneumonic lungs."}
{"id": "PMID:217144", "title": "[Serologic methods for the overall diagnosis of bovine herpes mamillitis].", "content": "Developed were methods of seroneutralization, agar gel precipitation, and complement-fixation test (CFT) for the complex diagnosis of herpes mamillitis of herpes mamillitis in cattle. An agreement was found between the results obtained with the use of each method. Highest sensitivity and specificity possessed the seroneutralization reaction with which a highest percent of positively reacting sera was revealed (18.6). However, the CFT method could preferably be applied in mass investigations as it is more quickly and readily used as a screening test. By means of the agar gel precipitation and CFT methods the antigenic relatedness between Bovid herpesvirus 2 and the remaining representatives of the herpes virus group, and chiefly Human herpes virus 1, could be demonstrated.", "contents": "[Serologic methods for the overall diagnosis of bovine herpes mamillitis]. Developed were methods of seroneutralization, agar gel precipitation, and complement-fixation test (CFT) for the complex diagnosis of herpes mamillitis of herpes mamillitis in cattle. An agreement was found between the results obtained with the use of each method. Highest sensitivity and specificity possessed the seroneutralization reaction with which a highest percent of positively reacting sera was revealed (18.6). However, the CFT method could preferably be applied in mass investigations as it is more quickly and readily used as a screening test. By means of the agar gel precipitation and CFT methods the antigenic relatedness between Bovid herpesvirus 2 and the remaining representatives of the herpes virus group, and chiefly Human herpes virus 1, could be demonstrated."}
{"id": "PMID:217145", "title": "[Virus-neutralizing activity of colostral immunoglobulins in swine vaccinated with an inactivated vaccine against Aujeszky's disease virus].", "content": "Colostral globulins of sows immunized with an ethanol-saponin vaccine against Aujeszky's disease virus were fractionated through gel filtration by means of Sephadex-200. The virus-neutralizing activity of the globulin fractions identified through agar gel immunoelectrophoresis was evaluated by the virus-neutralizing test with cell cultures. The level of the antibodies found in class IgG substantially exceeded that of the IgA antibodies. It is believed that after muscular application of an ethanolsaponin vaccine against Aujeszky's disease the mammary gland of the vaccinated sows secretes virus-neutralizing antibodies mainly of the IgG class.", "contents": "[Virus-neutralizing activity of colostral immunoglobulins in swine vaccinated with an inactivated vaccine against Aujeszky's disease virus]. Colostral globulins of sows immunized with an ethanol-saponin vaccine against Aujeszky's disease virus were fractionated through gel filtration by means of Sephadex-200. The virus-neutralizing activity of the globulin fractions identified through agar gel immunoelectrophoresis was evaluated by the virus-neutralizing test with cell cultures. The level of the antibodies found in class IgG substantially exceeded that of the IgA antibodies. It is believed that after muscular application of an ethanolsaponin vaccine against Aujeszky's disease the mammary gland of the vaccinated sows secretes virus-neutralizing antibodies mainly of the IgG class."}
{"id": "PMID:217146", "title": "[Residues of the antifluke preparations, dovenix and acredist, in sheep milk and their effect on the biochemical blood indices of sheep].", "content": "The excretion of residual amounts of acedist and dovenix with the milk of sheep that had been treated with these preparations was established on the 24th, resp., up to the 27th day following treatment, though their presence in the milk was found to drop sharply after the third day. The treatment with acedist led to a dependable decrease (P less than 0.05) in the hemoglobin amount, the total protein, and the erythrocyte count, and a dependable increase (P less than 0.05) in the leukocyte count. The intensity of these changes subsided parallel to the decrease in the residual amounts of the preparation in the milk excreted. The treatment with dovenix did not result in any deviations of the indices refered to.", "contents": "[Residues of the antifluke preparations, dovenix and acredist, in sheep milk and their effect on the biochemical blood indices of sheep]. The excretion of residual amounts of acedist and dovenix with the milk of sheep that had been treated with these preparations was established on the 24th, resp., up to the 27th day following treatment, though their presence in the milk was found to drop sharply after the third day. The treatment with acedist led to a dependable decrease (P less than 0.05) in the hemoglobin amount, the total protein, and the erythrocyte count, and a dependable increase (P less than 0.05) in the leukocyte count. The intensity of these changes subsided parallel to the decrease in the residual amounts of the preparation in the milk excreted. The treatment with dovenix did not result in any deviations of the indices refered to."}
{"id": "PMID:217176", "title": "[Morphometric analysis of ultrastructure of human synovioma cells].", "content": "Under examination were two gigantic-cell benign synoviomas and seven synovial sarcomas, including two metastatic tumors. The most specific ultrastructural criterion allowing a judgement of the degree of malignancy of the neoplasm under study is a parameter characterizing the predominance of ergastoplasmic protein synthesis over polyribosomal one.", "contents": "[Morphometric analysis of ultrastructure of human synovioma cells]. Under examination were two gigantic-cell benign synoviomas and seven synovial sarcomas, including two metastatic tumors. The most specific ultrastructural criterion allowing a judgement of the degree of malignancy of the neoplasm under study is a parameter characterizing the predominance of ergastoplasmic protein synthesis over polyribosomal one."}
{"id": "PMID:217178", "title": "[Helper viruses of adeno-associated virus type 4 replication].", "content": "In replication of adeno-associated virus type 4 (AAV-4) the helper function may be performed by a non-defective virus from the same group of parvoviruses (Kilham virus). The synthesis of AAV-4 antigen was observed in a pig embryo kidney cell line, SPEV, chronically infected with Kilham virus, strain RV-13, 45--52 passages. A one-day-old SPEV-Kilham culture was infected with AAV-4. The AAV-4 antigen was detected by immunofluorescence at 6, 8, 12, 18 hours, 2, 3, 4, and 5 days after inoculation. During the first 2--4 days after inoculation the AAV-4 antigen was found in the nucleus and perinuclear zone, later in the cytoplasm. A \"new\" helper virus for AAV-4 replication has been found: simiancytomegalovirus in human embryo fibroblast cell culture permissive for the helper virus. In the systems where AAV-4 replicates, its antigen can be detected in the nucleus and perinuclear zone by IF. AAV-4 did not replicate in a system insensitive to the helper virus or under non-permissive conditions: at the time, the AAV-4 antigen localized only in the cell cytoplasm was detected.", "contents": "[Helper viruses of adeno-associated virus type 4 replication]. In replication of adeno-associated virus type 4 (AAV-4) the helper function may be performed by a non-defective virus from the same group of parvoviruses (Kilham virus). The synthesis of AAV-4 antigen was observed in a pig embryo kidney cell line, SPEV, chronically infected with Kilham virus, strain RV-13, 45--52 passages. A one-day-old SPEV-Kilham culture was infected with AAV-4. The AAV-4 antigen was detected by immunofluorescence at 6, 8, 12, 18 hours, 2, 3, 4, and 5 days after inoculation. During the first 2--4 days after inoculation the AAV-4 antigen was found in the nucleus and perinuclear zone, later in the cytoplasm. A \"new\" helper virus for AAV-4 replication has been found: simiancytomegalovirus in human embryo fibroblast cell culture permissive for the helper virus. In the systems where AAV-4 replicates, its antigen can be detected in the nucleus and perinuclear zone by IF. AAV-4 did not replicate in a system insensitive to the helper virus or under non-permissive conditions: at the time, the AAV-4 antigen localized only in the cell cytoplasm was detected."}
{"id": "PMID:217183", "title": "[Dacarbacinum (DTIC) and bronchogenic carcinoma (author's transl)].", "content": "A pilot study is reported on the results achieved with the cytostatic agent dacarbacinum (DTIC) on previously untreated, inoperable bronchogenic carcinomas which had been histologically and/or cytologically verified. Altogether there were 16 patients, i.e. 13 males and 3 females. DTIC monotherapy was administered to 14 patients; one patient received additionally vitamin A in high dosage and a further patient VP 16 (a podophyllotoxin preparation). The achieved results (a remission rate of 50%) justify the further application of this agent, whereby its relatively limited side effects as well as goood tolerability in elderly patients (over 70 years of age) are emphasized. The inclusion of the preparation in effective combinations is discussed.", "contents": "[Dacarbacinum (DTIC) and bronchogenic carcinoma (author's transl)]. A pilot study is reported on the results achieved with the cytostatic agent dacarbacinum (DTIC) on previously untreated, inoperable bronchogenic carcinomas which had been histologically and/or cytologically verified. Altogether there were 16 patients, i.e. 13 males and 3 females. DTIC monotherapy was administered to 14 patients; one patient received additionally vitamin A in high dosage and a further patient VP 16 (a podophyllotoxin preparation). The achieved results (a remission rate of 50%) justify the further application of this agent, whereby its relatively limited side effects as well as goood tolerability in elderly patients (over 70 years of age) are emphasized. The inclusion of the preparation in effective combinations is discussed."}
{"id": "PMID:217182", "title": "Pneumocystis carinii, Toxoplasma gondii, Cytomegalovirus and the compromised host.", "content": "Pneumocystis carinii and Toxoplasma gondii are the two major parasitic protozoan pathogens in the immunocompromised host. Both organisms cause latent infection in humans and many animals. Cats are the definitive hosts for toxoplasmosis; the animal vector for pneumocystis (if any) has not been defined. Toxoplasma is an obligate intracellular parasite, whereas the available evidence suggests that Pneumocystis carinii exists primarily extracellularly. In compromised hosts, pneumocystis infection usually involves only lungs, whereas toxoplasma causes a generalized infection with encephalitis being the principal clinical manifestation. Both types of infection are treated with combinations of folate antagonists (trimethoprim or pyrimethamine with sulfonamide). Both parasites are associated with cytomegalovirus infection in immunosuppressed hosts, an association which may be due to symbiosis between parasites, or to an additive immunosuppressive effect of dual infection on the hosts.", "contents": "Pneumocystis carinii, Toxoplasma gondii, Cytomegalovirus and the compromised host. Pneumocystis carinii and Toxoplasma gondii are the two major parasitic protozoan pathogens in the immunocompromised host. Both organisms cause latent infection in humans and many animals. Cats are the definitive hosts for toxoplasmosis; the animal vector for pneumocystis (if any) has not been defined. Toxoplasma is an obligate intracellular parasite, whereas the available evidence suggests that Pneumocystis carinii exists primarily extracellularly. In compromised hosts, pneumocystis infection usually involves only lungs, whereas toxoplasma causes a generalized infection with encephalitis being the principal clinical manifestation. Both types of infection are treated with combinations of folate antagonists (trimethoprim or pyrimethamine with sulfonamide). Both parasites are associated with cytomegalovirus infection in immunosuppressed hosts, an association which may be due to symbiosis between parasites, or to an additive immunosuppressive effect of dual infection on the hosts."}
{"id": "PMID:217179", "title": "[Characteristics of the response of mice with temporary immunodepression to the administration of live or inactivated vaccine against tick-borne encephalitis].", "content": "Mice with immunity defects caused by administration of cyclophosphane were inoculated with an inactivated vaccine or Langat virus (TP-21 strain) considered to be an approximate model of the vaccine against tick-borne encephalitis. In mice with depressed immune response, the asymptomatic infection caused by Langat virus turns into acute form and encephalitis with a fatal outcome develops in 86--100%. Pre-treatment with inactivated tick-borne encephalitis vaccine did not protect the animals with the immunity defect against neuroinfection induced by subsequent inoculation with Langat or tick-borne encephalitis virus. The experimental results suggest that the use of a live vaccine against tick-borne encephalitis in specimens with immunity defects is very dangerous because of the possibility of affection of the central nervous system.", "contents": "[Characteristics of the response of mice with temporary immunodepression to the administration of live or inactivated vaccine against tick-borne encephalitis]. Mice with immunity defects caused by administration of cyclophosphane were inoculated with an inactivated vaccine or Langat virus (TP-21 strain) considered to be an approximate model of the vaccine against tick-borne encephalitis. In mice with depressed immune response, the asymptomatic infection caused by Langat virus turns into acute form and encephalitis with a fatal outcome develops in 86--100%. Pre-treatment with inactivated tick-borne encephalitis vaccine did not protect the animals with the immunity defect against neuroinfection induced by subsequent inoculation with Langat or tick-borne encephalitis virus. The experimental results suggest that the use of a live vaccine against tick-borne encephalitis in specimens with immunity defects is very dangerous because of the possibility of affection of the central nervous system."}
{"id": "PMID:217185", "title": "Kinetic investigations of the autoxidation of adrenalin.", "content": "Generation rates of superoxide anions (O2-) by autoxidizing adrenalin at pH 9.5 were determined in solutions containing either superoxide dismutase (0.85 M-1 S-1) or hydroxylamine (0.0185 M-1 S-1) as competitive scavengers. The rate constants of O2- with adrenalin and hydroxylamine were calculated for neutral and alkaline solutions. The respective values were for adrenalin: 5.6 X 10(4) M-1 S-1, pH 7.8; 7.0 X 10(3) M-1 S-1, pH 9.5--and for hydroxylamine 5.9 X 10(4) M-1 S-1, pH 7.8; 3.4 X 10(4) M-1 S-1, pH 9.5. The effects of various competitors and O2- sources on the rate constants were compared.", "contents": "Kinetic investigations of the autoxidation of adrenalin. Generation rates of superoxide anions (O2-) by autoxidizing adrenalin at pH 9.5 were determined in solutions containing either superoxide dismutase (0.85 M-1 S-1) or hydroxylamine (0.0185 M-1 S-1) as competitive scavengers. The rate constants of O2- with adrenalin and hydroxylamine were calculated for neutral and alkaline solutions. The respective values were for adrenalin: 5.6 X 10(4) M-1 S-1, pH 7.8; 7.0 X 10(3) M-1 S-1, pH 9.5--and for hydroxylamine 5.9 X 10(4) M-1 S-1, pH 7.8; 3.4 X 10(4) M-1 S-1, pH 9.5. The effects of various competitors and O2- sources on the rate constants were compared."}
{"id": "PMID:217204", "title": "[Prenatal diagnosis of malformations by ultrasound (author's transl)].", "content": "The significance of ultrasound diagnosis for the detection of fetal malformations will be demonstrated in 66 cases. The group includes hydrocephaly, anencephaly, microcephaly, synostosis praematura, cleft of the face, spina bifida, omphalocoele, Potter's syndrome, Down's syndrome, Klinefelter's syndrome, Vrolik's syndrome, triploidy, adenomatoide cystic malformation of the lungs, malformation of the heart and the limbs. Typical echographic findings are demonstrated. In regard to normal fetuses, head and trunk measurements will be analysed. Suspicious symptomes for the presence of malformations will be mentioned and also difficulties for the diagnosis of anencephaly and hydrocephaly. Furthermore typical findings in early pregnancy failure resulting from malformation are discussed.", "contents": "[Prenatal diagnosis of malformations by ultrasound (author's transl)]. The significance of ultrasound diagnosis for the detection of fetal malformations will be demonstrated in 66 cases. The group includes hydrocephaly, anencephaly, microcephaly, synostosis praematura, cleft of the face, spina bifida, omphalocoele, Potter's syndrome, Down's syndrome, Klinefelter's syndrome, Vrolik's syndrome, triploidy, adenomatoide cystic malformation of the lungs, malformation of the heart and the limbs. Typical echographic findings are demonstrated. In regard to normal fetuses, head and trunk measurements will be analysed. Suspicious symptomes for the presence of malformations will be mentioned and also difficulties for the diagnosis of anencephaly and hydrocephaly. Furthermore typical findings in early pregnancy failure resulting from malformation are discussed."}
{"id": "PMID:217203", "title": "Collagenase-induced experimental arthritis.", "content": "Rabbits were injected intraarticularly three times with 0.5 ml of 10, 50 or 100 mg% purified rheumatoid synovial collagenase or with identical amounts of trypsin. 18 hours after the last injection the collagenase-injected animals showed distinct cellular exudation into the synovial fluid and acute arthritis; one week later there was a decrease of the cell count in the synovial fluid and appearance of proliferative synovitis, while 3 weeks later there was no exudation and less chronic inflammation but distinct fibrosis of the synovium. A direct action of collagenase on the connective tissue components would seem to be responsible for these changes. No pathologic alteration of the cartilage was observed. Trypsin-injected control animals showed negligible cellular exudation and no pathologic alteration of the synovium.", "contents": "Collagenase-induced experimental arthritis. Rabbits were injected intraarticularly three times with 0.5 ml of 10, 50 or 100 mg% purified rheumatoid synovial collagenase or with identical amounts of trypsin. 18 hours after the last injection the collagenase-injected animals showed distinct cellular exudation into the synovial fluid and acute arthritis; one week later there was a decrease of the cell count in the synovial fluid and appearance of proliferative synovitis, while 3 weeks later there was no exudation and less chronic inflammation but distinct fibrosis of the synovium. A direct action of collagenase on the connective tissue components would seem to be responsible for these changes. No pathologic alteration of the cartilage was observed. Trypsin-injected control animals showed negligible cellular exudation and no pathologic alteration of the synovium."}
{"id": "PMID:217209", "title": "[Comparative study of smallpox vaccines from strains B-51, EM-63 and L-IVP in a controlled epidemiologic trial. I. Reactogenic characteristics of the smallpox vaccines].", "content": "A comparative study of smallpox vaccines prepared from the l-ivp zm-63 and b-51 strains was carried out under conditions of controlled epidemiological trial. Children subject to planned vaccination were scarified with commercial batches of the preparations under study (with the same infectious activity). As a result of investigations it was found that in the group of those scarified with the vaccine from zm-63 strain strong local and catarrhal reactions and some disturbances of general condition were more frequent than in those scarified with preparations from the l-ivp and b-51 strain. Along with this, the temperature elevation of various intensity showed no statistically significant difference in the groups a vaccinated with the vaccines compared. Integral analysis of signs characterising different manifestations of reactigenic properties of the vaccines compared led to the conclusion that preparations made of zm-6 strain had greater reactogenic properties.", "contents": "[Comparative study of smallpox vaccines from strains B-51, EM-63 and L-IVP in a controlled epidemiologic trial. I. Reactogenic characteristics of the smallpox vaccines]. A comparative study of smallpox vaccines prepared from the l-ivp zm-63 and b-51 strains was carried out under conditions of controlled epidemiological trial. Children subject to planned vaccination were scarified with commercial batches of the preparations under study (with the same infectious activity). As a result of investigations it was found that in the group of those scarified with the vaccine from zm-63 strain strong local and catarrhal reactions and some disturbances of general condition were more frequent than in those scarified with preparations from the l-ivp and b-51 strain. Along with this, the temperature elevation of various intensity showed no statistically significant difference in the groups a vaccinated with the vaccines compared. Integral analysis of signs characterising different manifestations of reactigenic properties of the vaccines compared led to the conclusion that preparations made of zm-6 strain had greater reactogenic properties."}
{"id": "PMID:217210", "title": "[Results of a study of acute paretic diseases in children according to material from a epidemiologic examination of the foci].", "content": "The authors carried out epidemiological examination of 160 foci of acute paretic diseases (APD) with serovirological examination of 181 patients and 413 contacts. Polioviruses were found to be etiologically responsible for the disease, as indicated by the results of serological examination in 37% of the patients, and by isolation of polioviruses (of the I and III types) in 4% of cases. As revealed, the vaccination scheme (periods and number of vaccinations) was not properly followed in 81.7% of those who contracted the disease. There were some differences in the characteristics of the foci in the child collective bodies and in families. Only individual cases of the disease were as a rule revealed in the familial foci, whereas in 9.6% of creches and kindergartens there were from 2 to 4 cases in each focus.", "contents": "[Results of a study of acute paretic diseases in children according to material from a epidemiologic examination of the foci]. The authors carried out epidemiological examination of 160 foci of acute paretic diseases (APD) with serovirological examination of 181 patients and 413 contacts. Polioviruses were found to be etiologically responsible for the disease, as indicated by the results of serological examination in 37% of the patients, and by isolation of polioviruses (of the I and III types) in 4% of cases. As revealed, the vaccination scheme (periods and number of vaccinations) was not properly followed in 81.7% of those who contracted the disease. There were some differences in the characteristics of the foci in the child collective bodies and in families. Only individual cases of the disease were as a rule revealed in the familial foci, whereas in 9.6% of creches and kindergartens there were from 2 to 4 cases in each focus."}
{"id": "PMID:217211", "title": "The role of cyclic nucleotides and prostaglandins in heart function.", "content": "A short review of the role of cyclic nucleotides and prostaglandins (PGs) in normal and pathological functions of the heart is given. Possible interrelationships of these two regulatory systems have been studied by using spontaneously beating rat atria preparations. Addition of noradrenaline (NA) to the incubate (1 . 10(-6) M) caused an increase in amplitude and frequency which was preceded and parallelled by an elevation of the tissue cAMP level. A transient increase in cGMP and PGE values was also seen. Propranolol (5 . 10(-6) M) abolished the increase in amplitude and frequency as well as in cAMP and PGE concentrations. Indomethacin (1 . 10(-5) M) inhibited the formation of PGE. The increase in cGMP was blocked by phenoxybenzamine. Interchange between beta- and alpha-receptors according as the temperature is lowered has been described earlier. Hypothermia (20 degrees C) had a positive inotropic effect on the atria and increased the tissue cAMP concentration. Loading of the atria caused an increase in cAMP without any effects on cGMP or PGs. Slight hypoxia did not change the cAMP or PG levels, but elevated the cGMP values. Arrhythmias induced by hypo- or hyperpotassemia did not modify the biochemical parameters measured. PGF2alpha (1. 10(-5) M) normalized the atrial rhythm and increased the amplitude without changing cyclic nucleotide or PG levels. PGE1 (1 . 10(-4) M) increased the amplitude of normorhythmic atria and the tissue concentration of cAMP. PGE2 was the only PG tested which stimulated the heart adenylate cyclase in vitro. There seems to be close but complicated relationships between cyclic nucleotides and PGs in the heart.", "contents": "The role of cyclic nucleotides and prostaglandins in heart function. A short review of the role of cyclic nucleotides and prostaglandins (PGs) in normal and pathological functions of the heart is given. Possible interrelationships of these two regulatory systems have been studied by using spontaneously beating rat atria preparations. Addition of noradrenaline (NA) to the incubate (1 . 10(-6) M) caused an increase in amplitude and frequency which was preceded and parallelled by an elevation of the tissue cAMP level. A transient increase in cGMP and PGE values was also seen. Propranolol (5 . 10(-6) M) abolished the increase in amplitude and frequency as well as in cAMP and PGE concentrations. Indomethacin (1 . 10(-5) M) inhibited the formation of PGE. The increase in cGMP was blocked by phenoxybenzamine. Interchange between beta- and alpha-receptors according as the temperature is lowered has been described earlier. Hypothermia (20 degrees C) had a positive inotropic effect on the atria and increased the tissue cAMP concentration. Loading of the atria caused an increase in cAMP without any effects on cGMP or PGs. Slight hypoxia did not change the cAMP or PG levels, but elevated the cGMP values. Arrhythmias induced by hypo- or hyperpotassemia did not modify the biochemical parameters measured. PGF2alpha (1. 10(-5) M) normalized the atrial rhythm and increased the amplitude without changing cyclic nucleotide or PG levels. PGE1 (1 . 10(-4) M) increased the amplitude of normorhythmic atria and the tissue concentration of cAMP. PGE2 was the only PG tested which stimulated the heart adenylate cyclase in vitro. There seems to be close but complicated relationships between cyclic nucleotides and PGs in the heart."}
{"id": "PMID:217212", "title": "Effects of exogenous prostaglandin E1 on human plasma norepinephrine level and dopamine-beta-hydrolyxase activity.", "content": "Effects of exogenous PG E1 on the level of human plasma norepinephrine (NE), dopamine-beta-hydroxylase (DBH) activity, cAMP, cGMP, free fatty acids (FFA) as well as pulse rate and blood pressure were studied. Significant decreases of blood pressure and increases of pulse rate were observed after 20 min of the infusion of 0.05 microgram/kg/min of PG E1. The level of plasma NE increased by 174% (p less than 0.005) after the infusion. However, the increase of DBH activity was not significant. There was a tendency of increase of plasma level of FFA. These results suggested that the infusion of PG E1 caused an augmented sympathetic nervous activity due to systemic hypotension induced by PG E1.", "contents": "Effects of exogenous prostaglandin E1 on human plasma norepinephrine level and dopamine-beta-hydrolyxase activity. Effects of exogenous PG E1 on the level of human plasma norepinephrine (NE), dopamine-beta-hydroxylase (DBH) activity, cAMP, cGMP, free fatty acids (FFA) as well as pulse rate and blood pressure were studied. Significant decreases of blood pressure and increases of pulse rate were observed after 20 min of the infusion of 0.05 microgram/kg/min of PG E1. The level of plasma NE increased by 174% (p less than 0.005) after the infusion. However, the increase of DBH activity was not significant. There was a tendency of increase of plasma level of FFA. These results suggested that the infusion of PG E1 caused an augmented sympathetic nervous activity due to systemic hypotension induced by PG E1."}
{"id": "PMID:217213", "title": "On the histochemistry of prostaglandin-dehydrogenase.", "content": "Using PGF2alpha as substrate the PGDH-activity was localised in the male and in the female rat kidney by histochemical technique. The reaction is independent of the presence of NAD, but with NAD the reaction intensity is enhanced. The effectors phenazine methosulphate, Triton X 100 and Tween 80 showed no enhancing effect on the enzyme activity. In the rat kidney we have found the reaction product predominantly in the inner cortex (straight portion of the proximal tubules), however, sex dependent differences of PGDH-activity and localization are visible.", "contents": "On the histochemistry of prostaglandin-dehydrogenase. Using PGF2alpha as substrate the PGDH-activity was localised in the male and in the female rat kidney by histochemical technique. The reaction is independent of the presence of NAD, but with NAD the reaction intensity is enhanced. The effectors phenazine methosulphate, Triton X 100 and Tween 80 showed no enhancing effect on the enzyme activity. In the rat kidney we have found the reaction product predominantly in the inner cortex (straight portion of the proximal tubules), however, sex dependent differences of PGDH-activity and localization are visible."}
{"id": "PMID:217214", "title": "Effects of alpha- and beta-adrenergic blockers on binding of thyrotrophin to fat cell membrane.", "content": "Alpha- (phentolamine) and beta-adrenergic blocking agents (propranolol) and quinidine similarly enhance the specific binding of TSH to the guinea pig fat cell membranes over the concentration range of 2 X 10(-4) to 4 X 10(-3) M, increasing the binding affinity of TSH to the membranes. The percentage bound increased from 8% in the absence of agents to 32% (phentolamine), 29% (propranolol) and 24% (quinidine), respectively in the presence of these agents (1.5 X 10(-3) M). Each minimal detectable quantity of TSH was approximately 10 microU per tube in the presence of these agents (10(-3) M) as compared to 100 microU per tube in their absence. Both phentolamine and propranolol appeared to enhance the TSH binding to fat cell membranes through membrane-active, non-specific effects besides their alpha- and beta-adrenergic blocking activities.", "contents": "Effects of alpha- and beta-adrenergic blockers on binding of thyrotrophin to fat cell membrane. Alpha- (phentolamine) and beta-adrenergic blocking agents (propranolol) and quinidine similarly enhance the specific binding of TSH to the guinea pig fat cell membranes over the concentration range of 2 X 10(-4) to 4 X 10(-3) M, increasing the binding affinity of TSH to the membranes. The percentage bound increased from 8% in the absence of agents to 32% (phentolamine), 29% (propranolol) and 24% (quinidine), respectively in the presence of these agents (1.5 X 10(-3) M). Each minimal detectable quantity of TSH was approximately 10 microU per tube in the presence of these agents (10(-3) M) as compared to 100 microU per tube in their absence. Both phentolamine and propranolol appeared to enhance the TSH binding to fat cell membranes through membrane-active, non-specific effects besides their alpha- and beta-adrenergic blocking activities."}
{"id": "PMID:217215", "title": "Ovarian binding and intrinsic biological activity of desialylated human chorionic gonadothrophin (ASIALO-hCG).", "content": "The present study was undertaken to investigate the effect of desialylation on the intrinsic in vivo biological activity of hCG. To block the hepatic uptake of asialo-hCG we investigated asialo-orosomucoid. The biological activity of hCG and asialo-hCG was estimated with the ovarian ascorbic acid depletion assay (OAAD). The uptake studies were performed with [125I]hCG and [125I]asialo-hCG. Desialylation of hCG increased its hepatic uptake, almost completely abolished its ovarian uptake, and reduced its in vivo biological activity to less than 1%. Administration of asialo-orosomucoid caused a reduction of the hepatic uptake of asialo-hCG to the level observed for hCG. The ovarian uptake increased, but was lower than observed for hCG, due to a considerably higher renal accumulation of asialo-hCG. The in vivo biological activity of asialo-hCG was approximately 1/5 of the activity of hCG when both were tested in the presence of asialo-orosomucoid. To exclude the interference of renal accumulation, binding and biological activity were also investigated after bilateral nephrectomy. The uptake of radioactivity in the ovaries following injection of [512I]asialo-hCG and asialo-orosomucoid was then almost the same as observed after injection of [125I]hCG alone. When both preparations were now tested in the presence of asialo-orosomucoid, the in vivo biological activity of asialo-hCG appeared to be approximately 1/3 of the value obtained for hCG. It is concluded that the intrinsic in vivo biological activity of hCG is lowered by desialylation.", "contents": "Ovarian binding and intrinsic biological activity of desialylated human chorionic gonadothrophin (ASIALO-hCG). The present study was undertaken to investigate the effect of desialylation on the intrinsic in vivo biological activity of hCG. To block the hepatic uptake of asialo-hCG we investigated asialo-orosomucoid. The biological activity of hCG and asialo-hCG was estimated with the ovarian ascorbic acid depletion assay (OAAD). The uptake studies were performed with [125I]hCG and [125I]asialo-hCG. Desialylation of hCG increased its hepatic uptake, almost completely abolished its ovarian uptake, and reduced its in vivo biological activity to less than 1%. Administration of asialo-orosomucoid caused a reduction of the hepatic uptake of asialo-hCG to the level observed for hCG. The ovarian uptake increased, but was lower than observed for hCG, due to a considerably higher renal accumulation of asialo-hCG. The in vivo biological activity of asialo-hCG was approximately 1/5 of the activity of hCG when both were tested in the presence of asialo-orosomucoid. To exclude the interference of renal accumulation, binding and biological activity were also investigated after bilateral nephrectomy. The uptake of radioactivity in the ovaries following injection of [512I]asialo-hCG and asialo-orosomucoid was then almost the same as observed after injection of [125I]hCG alone. When both preparations were now tested in the presence of asialo-orosomucoid, the in vivo biological activity of asialo-hCG appeared to be approximately 1/3 of the value obtained for hCG. It is concluded that the intrinsic in vivo biological activity of hCG is lowered by desialylation."}
{"id": "PMID:217216", "title": "Myeloperoxidase activity and bactericidal function of PMN in iron deficiency.", "content": "In children with iron deficiency anemia, bactericidal capacity of polymorphonuclear leukocytes (PMN) and serum opsonic activity were studied. Nitroblue tetrazolium test (NBT), hexose monophosphate (HMP) shunt activation, and myeloperoxidase (MPO) activity of PMN of these cases were also examined. Bactericidal capacity and HMP shunt activation were found to be decreased in iron deficiency anemia ( p less than 0.001). MPO activity, NBT test, and serum opsonic activity were found to be within normal limits. After 1 1/2 months of iron therapy there was an improvement in bactericidal capacity and it returned to a normal level after 3 months of therapy.", "contents": "Myeloperoxidase activity and bactericidal function of PMN in iron deficiency. In children with iron deficiency anemia, bactericidal capacity of polymorphonuclear leukocytes (PMN) and serum opsonic activity were studied. Nitroblue tetrazolium test (NBT), hexose monophosphate (HMP) shunt activation, and myeloperoxidase (MPO) activity of PMN of these cases were also examined. Bactericidal capacity and HMP shunt activation were found to be decreased in iron deficiency anemia ( p less than 0.001). MPO activity, NBT test, and serum opsonic activity were found to be within normal limits. After 1 1/2 months of iron therapy there was an improvement in bactericidal capacity and it returned to a normal level after 3 months of therapy."}
{"id": "PMID:217217", "title": "Haemoglobin Barts in newborn Tanzanians.", "content": "Using both starch gel and cellulose-acetate electrophoresis is screening procedures, haemoglobin (Hb) Barts was detected in 11.08% of 325 cord blood samples from newborn Tanzanians. Red cell studies in these and in normals and a search for inclusion bodies of Hb H did not suggest alpha-thalassaemia. The mothers of these babies do not show any evidence of alpha-thalassaemia. It is suggested that the presence of Hb Barts in samples of cord blood is not due to the presence of alpha-thalassaemia in the Tanzanian population.", "contents": "Haemoglobin Barts in newborn Tanzanians. Using both starch gel and cellulose-acetate electrophoresis is screening procedures, haemoglobin (Hb) Barts was detected in 11.08% of 325 cord blood samples from newborn Tanzanians. Red cell studies in these and in normals and a search for inclusion bodies of Hb H did not suggest alpha-thalassaemia. The mothers of these babies do not show any evidence of alpha-thalassaemia. It is suggested that the presence of Hb Barts in samples of cord blood is not due to the presence of alpha-thalassaemia in the Tanzanian population."}
{"id": "PMID:217218", "title": "A controlled study of the effect of sulfinpyrazone on platelet survival and on platelet-bound 14C-serotonin release in patients with previous myocardial infarction.", "content": "Preliminary data obtained in the ambit of Anturan Reinfarction Italian Study (ARIS) show that, in postmyocardial infarction, reduced platelet survival time occurred in hyperbetalipoproteinemic patients treated with placebo, but not in the group of patients treated with sulfinpyrazone (interaction between treatment and lipemic level is at p approximately equal to 0.1). The sulfinpyrazone effect on platelet survival is probably related to the release reaction inhibition as suggested by our ex vivo results on platelet-bound 14C-serotonin release.", "contents": "A controlled study of the effect of sulfinpyrazone on platelet survival and on platelet-bound 14C-serotonin release in patients with previous myocardial infarction. Preliminary data obtained in the ambit of Anturan Reinfarction Italian Study (ARIS) show that, in postmyocardial infarction, reduced platelet survival time occurred in hyperbetalipoproteinemic patients treated with placebo, but not in the group of patients treated with sulfinpyrazone (interaction between treatment and lipemic level is at p approximately equal to 0.1). The sulfinpyrazone effect on platelet survival is probably related to the release reaction inhibition as suggested by our ex vivo results on platelet-bound 14C-serotonin release."}
{"id": "PMID:217219", "title": "Cytochemical localization of acid phosphatase and adenosine triphosphatase in some avian mechanoreceptors.", "content": "Ultrastructural distribution of acid phosphatase and adenosine triphosphatase was studied in the receptor elements of HERBST and GRANDRY sensory corpuscles. Acid phosphatase activity was established in the elements of smooth and rough endoplasmic reticulum of perineural capsule cells, as well as in the secondary lysosomes of all cell types. Particular interest was paid on the activity of myelin-like dense bodies and some clear core vesicles belonging to the axoplasm of receptor nerve fibres. Adenosine triphosphatase activity was established on the membranes of receptor structures and pinocytotic vesicles. More deposits of electron dense material were localized on the axolemma of the non-myelinated portions of the receptor nerve fibres. The functional significance and importance of the both enzymes in the receptor structures was discussed.", "contents": "Cytochemical localization of acid phosphatase and adenosine triphosphatase in some avian mechanoreceptors. Ultrastructural distribution of acid phosphatase and adenosine triphosphatase was studied in the receptor elements of HERBST and GRANDRY sensory corpuscles. Acid phosphatase activity was established in the elements of smooth and rough endoplasmic reticulum of perineural capsule cells, as well as in the secondary lysosomes of all cell types. Particular interest was paid on the activity of myelin-like dense bodies and some clear core vesicles belonging to the axoplasm of receptor nerve fibres. Adenosine triphosphatase activity was established on the membranes of receptor structures and pinocytotic vesicles. More deposits of electron dense material were localized on the axolemma of the non-myelinated portions of the receptor nerve fibres. The functional significance and importance of the both enzymes in the receptor structures was discussed."}
{"id": "PMID:217220", "title": "Effect of norepinephrine on myocardial reactive hyperaemia in the isolated fibrillating dog heart.", "content": "The effect of intracoronary norepinephrine (NE) infusion in a dose of 2 microgram/min on postocclusion hyperaemic reactions following occlusions of 15 sec, 30 sec, 60 sec, and 120 sec was studied on isolated fibrillating, blood-perfused canine hearts. Basal perfusion pressure was kept at the level of 150 mm Hg; perfusion was done with constant pressure or constant volume. During administration of NE, basal flow and basal coronary conductance increased with both perfusion techniques. In the postocclusion period during administration of NE, peak conductance, maximum conductance, reactivity, mean transit time of reactive hyperaemia, postocclusive conductance area and repayment decreased. The differences found in postocclusion reactions in the control state originated from the different perfusion techniques disappeared when NE was infused. The phenomena may be explained by the stimulation of alpha and beta receptors as well as of myocardial metabolism by NE. The results support earlier views which ascribe a decisive role to vasoactive metabolites in the postocclusion reaction after prolonged occlusions. The decrease in reactive hyperaemia by NE may contribute to the development of angina pectoris.", "contents": "Effect of norepinephrine on myocardial reactive hyperaemia in the isolated fibrillating dog heart. The effect of intracoronary norepinephrine (NE) infusion in a dose of 2 microgram/min on postocclusion hyperaemic reactions following occlusions of 15 sec, 30 sec, 60 sec, and 120 sec was studied on isolated fibrillating, blood-perfused canine hearts. Basal perfusion pressure was kept at the level of 150 mm Hg; perfusion was done with constant pressure or constant volume. During administration of NE, basal flow and basal coronary conductance increased with both perfusion techniques. In the postocclusion period during administration of NE, peak conductance, maximum conductance, reactivity, mean transit time of reactive hyperaemia, postocclusive conductance area and repayment decreased. The differences found in postocclusion reactions in the control state originated from the different perfusion techniques disappeared when NE was infused. The phenomena may be explained by the stimulation of alpha and beta receptors as well as of myocardial metabolism by NE. The results support earlier views which ascribe a decisive role to vasoactive metabolites in the postocclusion reaction after prolonged occlusions. The decrease in reactive hyperaemia by NE may contribute to the development of angina pectoris."}
{"id": "PMID:217221", "title": "Dissociation of the mitogenic and rosette-forming effects of PHA to stimulators of cyclic AMP levels.", "content": "The mitogenic and the spontaneous E-rosette stimulating effects of phytohaemagglutinin (PHA) were studied by examining their responses to an elevation of intracellular cAMP induced by pretreatment with aminophylline, adrenaline or PGE1 or by adding exogenous cAMP. Elevation of the intracellular cAMP levels of lymphocytes was found inhibitory to the mitogenic effect of PHA, while leaving the increased early and stable spontaneous rosette formation unaffected. It also failed to depress the PHA-induced slight increase in the proportion of total spontaneous E-rosette-forming lymphocytes. The responses of the two PHA effects under study to the elevation of the cAMP level are thus dissociated, suggesting that the two effects represent two different manifestations of lymphocyte activation, though these manifestations may not be independent of each other. It has been confirmed that PHA produces a shift primarily within the T-cell population toward the active and the stable E-rosette-forming subpopulation, while the increase in the total E-rosette-forming lymphocyte population is but slight. This may possibly involve the activation of the T-derived \"null\" cells unable to bind sheep red blood cells without PHA treatment.", "contents": "Dissociation of the mitogenic and rosette-forming effects of PHA to stimulators of cyclic AMP levels. The mitogenic and the spontaneous E-rosette stimulating effects of phytohaemagglutinin (PHA) were studied by examining their responses to an elevation of intracellular cAMP induced by pretreatment with aminophylline, adrenaline or PGE1 or by adding exogenous cAMP. Elevation of the intracellular cAMP levels of lymphocytes was found inhibitory to the mitogenic effect of PHA, while leaving the increased early and stable spontaneous rosette formation unaffected. It also failed to depress the PHA-induced slight increase in the proportion of total spontaneous E-rosette-forming lymphocytes. The responses of the two PHA effects under study to the elevation of the cAMP level are thus dissociated, suggesting that the two effects represent two different manifestations of lymphocyte activation, though these manifestations may not be independent of each other. It has been confirmed that PHA produces a shift primarily within the T-cell population toward the active and the stable E-rosette-forming subpopulation, while the increase in the total E-rosette-forming lymphocyte population is but slight. This may possibly involve the activation of the T-derived \"null\" cells unable to bind sheep red blood cells without PHA treatment."}
{"id": "PMID:217225", "title": "Neurofibrillary degeneration in a case of quadriplegia and myoclonic movement.", "content": "A case of spastic quadriplegia with myoclonic movement was studied by both light and electron microscope. Argentophilic inclusions were found in a unique distribution involving the cerebral cortex, brain stem, cerebellum, and the spinal cord, including the motor neuron system. The fine structure of the inclusions consisted of accumulation of previously undescribed straight or wavy tubules approximately 120A wide devoid of periodic constriction.", "contents": "Neurofibrillary degeneration in a case of quadriplegia and myoclonic movement. A case of spastic quadriplegia with myoclonic movement was studied by both light and electron microscope. Argentophilic inclusions were found in a unique distribution involving the cerebral cortex, brain stem, cerebellum, and the spinal cord, including the motor neuron system. The fine structure of the inclusions consisted of accumulation of previously undescribed straight or wavy tubules approximately 120A wide devoid of periodic constriction."}
{"id": "PMID:217228", "title": "Diagnostic evaluation of progesterone. Challenge test in amenorrheic patients.", "content": "Forty-one amenorrheic patients were grouped on the basis of presence or absence of withdrawal uterine bleeding following the intramuscular administration of progesterone. Ovarian volume, ovarian morphology with particular reference to presence or absence of follicles and state of follicular development, and steroidogenic function were investigated in each group. Most of amenorrheic patients with progesterone-induced uterine bleeding had relatively large ovaries with follicles of high developmental stage (tertiary-Graafian follicle) and responded to exogenously administered HMG and HCG with a rise in the 24-hour urinary excretion of total estrogens. In contrast, most of amenorrheic patients without progesterone-induced uterine bleeding had relatively small ovaries without follicles or with follicles of low developmental stage (primordial-secondary follicle) and did not respond to exogenous HMG and HCG. The results of the present study suggest that presence or absence of progesterone-induced uterine bleeding is closely correlated with the volume, morphology and steroidogenic function of the ovary in amenornorrheic patients. Thus, pathologic amenorrhea could be divided into two groups by utilizing the progesterone challenge test and this clinical categorization might be useful for the diagnosis and treatment of amenorrheic patients.", "contents": "Diagnostic evaluation of progesterone. Challenge test in amenorrheic patients. Forty-one amenorrheic patients were grouped on the basis of presence or absence of withdrawal uterine bleeding following the intramuscular administration of progesterone. Ovarian volume, ovarian morphology with particular reference to presence or absence of follicles and state of follicular development, and steroidogenic function were investigated in each group. Most of amenorrheic patients with progesterone-induced uterine bleeding had relatively large ovaries with follicles of high developmental stage (tertiary-Graafian follicle) and responded to exogenously administered HMG and HCG with a rise in the 24-hour urinary excretion of total estrogens. In contrast, most of amenorrheic patients without progesterone-induced uterine bleeding had relatively small ovaries without follicles or with follicles of low developmental stage (primordial-secondary follicle) and did not respond to exogenous HMG and HCG. The results of the present study suggest that presence or absence of progesterone-induced uterine bleeding is closely correlated with the volume, morphology and steroidogenic function of the ovary in amenornorrheic patients. Thus, pathologic amenorrhea could be divided into two groups by utilizing the progesterone challenge test and this clinical categorization might be useful for the diagnosis and treatment of amenorrheic patients."}
{"id": "PMID:217230", "title": "S-IgA cholera toxin and rotavirus antibody in human colostrum.", "content": "S-IgA antibodies against cholera toxin and rotavirus were assayed in 43 colostral samples by means of an enzyme-linked immunosorbent assay (ELISA). All specimens contained specific S-IgA antibodies against both antigens. Significant antibody titres to the antigens were demonstrated in almost all colostral samples.", "contents": "S-IgA cholera toxin and rotavirus antibody in human colostrum. S-IgA antibodies against cholera toxin and rotavirus were assayed in 43 colostral samples by means of an enzyme-linked immunosorbent assay (ELISA). All specimens contained specific S-IgA antibodies against both antigens. Significant antibody titres to the antigens were demonstrated in almost all colostral samples."}
{"id": "PMID:217231", "title": "Structural and functional abnormalities of the small intestine in infants and young children with rotavirus enteritis.", "content": "Structural and functional alterations in duodenal mucosa from 17 children with rotavirus enteritis were assessed. Structural changes were found in specimens from all patients. Patients with the most severe mucosal damage were more likely to require intravenous therapy to correct dehydration. Depression of one or more mucosal disaccharidases was found in 14 of 16 patients. Repeat duodenal biopsy three to eight weeks later in six patients showed marked improvement. The study clearly shows that rotavirus can cause a marked structural and functional lesion in the upper small intestine which is rapidly reversible.", "contents": "Structural and functional abnormalities of the small intestine in infants and young children with rotavirus enteritis. Structural and functional alterations in duodenal mucosa from 17 children with rotavirus enteritis were assessed. Structural changes were found in specimens from all patients. Patients with the most severe mucosal damage were more likely to require intravenous therapy to correct dehydration. Depression of one or more mucosal disaccharidases was found in 14 of 16 patients. Repeat duodenal biopsy three to eight weeks later in six patients showed marked improvement. The study clearly shows that rotavirus can cause a marked structural and functional lesion in the upper small intestine which is rapidly reversible."}
{"id": "PMID:217232", "title": "17-Hydroxyprogesterone in normal children and congenital adrenal hyperplasia. Measurement in serum by radioimmunoassay after thin-layer chromatography.", "content": "Serum 17alpha-hydroxyprogesterone (17 OH-P) was measured by a specific radioimmunoassay technique combined with thin-layer chromatography. Normal values for children are less than 1.1 microgram/1 (less than 3.3 nmol/l)--corresponding to values found in the literature. In congenital adrenal hyperplasia (CAH) values up to several hundred microgram/l are found. The values rise after ACTH stimulation and are suppressed by decadrone or cortisone treatment. The rise in 17 ketosteroids and pregnanetriol in untreated CAH is relatively smaller (15--25 fold). This clinical sensitivity of 17 OH-P is thus valuable for the diagnosis of CAH (21 hydroxylase deficiency). Furthermore it is easier to take a blood sample than to collect urine for 24 hours. The usefulness in therapeutic monitoring is being studied.", "contents": "17-Hydroxyprogesterone in normal children and congenital adrenal hyperplasia. Measurement in serum by radioimmunoassay after thin-layer chromatography. Serum 17alpha-hydroxyprogesterone (17 OH-P) was measured by a specific radioimmunoassay technique combined with thin-layer chromatography. Normal values for children are less than 1.1 microgram/1 (less than 3.3 nmol/l)--corresponding to values found in the literature. In congenital adrenal hyperplasia (CAH) values up to several hundred microgram/l are found. The values rise after ACTH stimulation and are suppressed by decadrone or cortisone treatment. The rise in 17 ketosteroids and pregnanetriol in untreated CAH is relatively smaller (15--25 fold). This clinical sensitivity of 17 OH-P is thus valuable for the diagnosis of CAH (21 hydroxylase deficiency). Furthermore it is easier to take a blood sample than to collect urine for 24 hours. The usefulness in therapeutic monitoring is being studied."}
{"id": "PMID:217233", "title": "Growth hormone response to prostaglandin E2.", "content": "C-AMP causes release of growth hormone from the pituitary. Prostaglandin increases pituitary adenylate cyclase and C-AMP and therefore acts like a growth hormone-releasing hormone. Using PGE2 (30 microgram per kilo body weight) given intravenously we have demonstrated that in no case was there a growth hormone response to insulin hypoglycaemia when PGE2 failed to evoke a response. However in 6 of 18 patients unresponsive to insulin hypoglycaemia a significant rise in growth hormone was obtained from PGE2. We argue that in these 6 patients hypothalamic unresponsiveness to hypoglycaemia must be operative whereas PGE2 acting directly at pituitary level is likely to have caused the release of preformed growth hormone from the pituitary. Administration of PGE2 does not cause hypoglycaemia but rather a slight rise in the plasma glucose level. Thus the risk of brain damage which is inherent in the insulin hypoglycaemia test is avoided.", "contents": "Growth hormone response to prostaglandin E2. C-AMP causes release of growth hormone from the pituitary. Prostaglandin increases pituitary adenylate cyclase and C-AMP and therefore acts like a growth hormone-releasing hormone. Using PGE2 (30 microgram per kilo body weight) given intravenously we have demonstrated that in no case was there a growth hormone response to insulin hypoglycaemia when PGE2 failed to evoke a response. However in 6 of 18 patients unresponsive to insulin hypoglycaemia a significant rise in growth hormone was obtained from PGE2. We argue that in these 6 patients hypothalamic unresponsiveness to hypoglycaemia must be operative whereas PGE2 acting directly at pituitary level is likely to have caused the release of preformed growth hormone from the pituitary. Administration of PGE2 does not cause hypoglycaemia but rather a slight rise in the plasma glucose level. Thus the risk of brain damage which is inherent in the insulin hypoglycaemia test is avoided."}
{"id": "PMID:217234", "title": "Bilateral bone-marrow examinations in small-cell anaplastic carcinoma of the lung.", "content": "Bilateral bone-marrow examinations from the posterior iliac crests were routinely performed as a pretreatment staging procedure in 89 consecutive patients with small-cell anaplastic carcinoma of the lung. Bone-marrow involvement was found in 20 patients (22.5%), in 9 (10.1%) only on one side, and in 11 (12.4%) on both sides. Aspiration was found to be significantly superior to biopsy, being positive in 25 examinations as compared with 14 positive biopsies. Compared with unilateral bone-marrow examination the positive findings increased by approximately 30%. Bilateral bone-marrow examinations are recommended in patients in whom the detection of bone-marrow metastases will have therapeutic implications.", "contents": "Bilateral bone-marrow examinations in small-cell anaplastic carcinoma of the lung. Bilateral bone-marrow examinations from the posterior iliac crests were routinely performed as a pretreatment staging procedure in 89 consecutive patients with small-cell anaplastic carcinoma of the lung. Bone-marrow involvement was found in 20 patients (22.5%), in 9 (10.1%) only on one side, and in 11 (12.4%) on both sides. Aspiration was found to be significantly superior to biopsy, being positive in 25 examinations as compared with 14 positive biopsies. Compared with unilateral bone-marrow examination the positive findings increased by approximately 30%. Bilateral bone-marrow examinations are recommended in patients in whom the detection of bone-marrow metastases will have therapeutic implications."}
{"id": "PMID:217235", "title": "Influence of 4-aminopyrazolopyrimidine on morphology, synthesis of triglyceride and protein and their secretion in rat hepatocytes.", "content": "The influence of 4-aminopyrazolopyrimidine (4-APP) on morphology and on synthesis and secretion ability of isolated rat hepatocytes was investigated: 4-APP was found to inhibit both the synthesis and secretion of proteins. The synthesis of triglycerides was unaffected by 4-APP, while the secretion of triglycerides was markedly reduced. Transmission electron microscopy revealed that 4-APP induced morphological changes in the smooth membrane systems, the smooth endoplasmic reticulum and the Golgi apparatus. The possibility that 4-APP inhibits lipoprotein formation by inhibition of the apoprotein synthesis is discussed.", "contents": "Influence of 4-aminopyrazolopyrimidine on morphology, synthesis of triglyceride and protein and their secretion in rat hepatocytes. The influence of 4-aminopyrazolopyrimidine (4-APP) on morphology and on synthesis and secretion ability of isolated rat hepatocytes was investigated: 4-APP was found to inhibit both the synthesis and secretion of proteins. The synthesis of triglycerides was unaffected by 4-APP, while the secretion of triglycerides was markedly reduced. Transmission electron microscopy revealed that 4-APP induced morphological changes in the smooth membrane systems, the smooth endoplasmic reticulum and the Golgi apparatus. The possibility that 4-APP inhibits lipoprotein formation by inhibition of the apoprotein synthesis is discussed."}
{"id": "PMID:217239", "title": "Possible role of thiamine in neuromuscular transmission.", "content": "Pyrithiamine (50 mg/kg), a thiamine antagonist, decreased the muscle twitches of the rat masseter muscle at stimulation frequencies above 1 Hz 40--80 min after an i.v. injection. The post-tetanic potentiation (PTP) induced by nerve stimulation of the masseter muscle was abolished by pyrithiamine. Administration of thiamine restored the muscle twitches at stimulation frequencies above 1 Hz and the PTP. The muscle twitches elicited by direct muscle stimulation were not affected by pyrithiamine treatment. The abolishment of the PTP was accompanied by a decrease in thiamine and thiamine-diphosphate. The pyruvate level in the blood was unchanged after pyrithiamine treatment. Oxythiamine, on the other hand, had no effect on the PTP but increased the pyruvate level in the blood. Fern extract which contains thiaminase I also abolished the PTP--an effect reversible by the addition of thiamine. The frequency-induced depression of the muscle twitches induced by pyrithiamine was similar to the effect of low doses of d-tubocurarine (8 microgram/kg). The results support the hypothesis that thiamine may play a role in neuromuscular transmission.", "contents": "Possible role of thiamine in neuromuscular transmission. Pyrithiamine (50 mg/kg), a thiamine antagonist, decreased the muscle twitches of the rat masseter muscle at stimulation frequencies above 1 Hz 40--80 min after an i.v. injection. The post-tetanic potentiation (PTP) induced by nerve stimulation of the masseter muscle was abolished by pyrithiamine. Administration of thiamine restored the muscle twitches at stimulation frequencies above 1 Hz and the PTP. The muscle twitches elicited by direct muscle stimulation were not affected by pyrithiamine treatment. The abolishment of the PTP was accompanied by a decrease in thiamine and thiamine-diphosphate. The pyruvate level in the blood was unchanged after pyrithiamine treatment. Oxythiamine, on the other hand, had no effect on the PTP but increased the pyruvate level in the blood. Fern extract which contains thiaminase I also abolished the PTP--an effect reversible by the addition of thiamine. The frequency-induced depression of the muscle twitches induced by pyrithiamine was similar to the effect of low doses of d-tubocurarine (8 microgram/kg). The results support the hypothesis that thiamine may play a role in neuromuscular transmission."}
{"id": "PMID:217236", "title": "Effect of silicic acid on surface potential of erythrocytes.", "content": "A potential-generating effect of ortho-silicic acid on the surface potentials of erythrocyte membranes was demonstrated by a potentiometric method using platinum electrodes. With concentration rising from 10(-7) to 10(-4) the silicic acid reduced potential of washed erythrocytes which reached the final concentration a value about 36 mV. Higher concentrations of acid caused haemolysis.", "contents": "Effect of silicic acid on surface potential of erythrocytes. A potential-generating effect of ortho-silicic acid on the surface potentials of erythrocyte membranes was demonstrated by a potentiometric method using platinum electrodes. With concentration rising from 10(-7) to 10(-4) the silicic acid reduced potential of washed erythrocytes which reached the final concentration a value about 36 mV. Higher concentrations of acid caused haemolysis."}
{"id": "PMID:217241", "title": "Rapid increase of glycosaminoglycans in the aorta of hypercholesterolemic rats; a negative correlation with plasma HDL concentration.", "content": "Rats were kept either on a standard laboratory diet or a high cholesterol, olive oil diet for periods ranging from 1 day to 22 weeks. The effect of the high cholesterol, olive oil diet on the concentrations of cholesterol, glycosaminoglycans (GAGs) and collagen in aortic intima-media, were studied and the developing hyperlipidemia was characterized. The concentration of cholesterol in rat aorta was increased after 22 weeks' high cholesterol, olive oil diet, while collagen concentration was not affected. On the contrary, the concentration of aortic sulphated GAGs was significantly increased already after one week's high cholesterol, olive oil diet. The diet increased the formation of a cholesterol-rich very low density lipoprotein (VLDL), decreased high density lipoprotein (HDL)-associated cholesterol and phospholipids, but had virtually no effect on low density lipoprotein (LDL)-lipids. The concentrations of VLDL-cholesterol and -phospholipids showed positive correlations with the concentration of aortic GAGs (r = 0.89 and 0.83, respectively, P less than 0.05 for both). Stronger (negative) correlations were found between aortic GAGs and HDL-cholesterol and -phospholipids (r = 0.94 for both, P less than 0.01) suggesting that HDL may have a role in the control of arterial sulphated GAG concentration.", "contents": "Rapid increase of glycosaminoglycans in the aorta of hypercholesterolemic rats; a negative correlation with plasma HDL concentration. Rats were kept either on a standard laboratory diet or a high cholesterol, olive oil diet for periods ranging from 1 day to 22 weeks. The effect of the high cholesterol, olive oil diet on the concentrations of cholesterol, glycosaminoglycans (GAGs) and collagen in aortic intima-media, were studied and the developing hyperlipidemia was characterized. The concentration of cholesterol in rat aorta was increased after 22 weeks' high cholesterol, olive oil diet, while collagen concentration was not affected. On the contrary, the concentration of aortic sulphated GAGs was significantly increased already after one week's high cholesterol, olive oil diet. The diet increased the formation of a cholesterol-rich very low density lipoprotein (VLDL), decreased high density lipoprotein (HDL)-associated cholesterol and phospholipids, but had virtually no effect on low density lipoprotein (LDL)-lipids. The concentrations of VLDL-cholesterol and -phospholipids showed positive correlations with the concentration of aortic GAGs (r = 0.89 and 0.83, respectively, P less than 0.05 for both). Stronger (negative) correlations were found between aortic GAGs and HDL-cholesterol and -phospholipids (r = 0.94 for both, P less than 0.01) suggesting that HDL may have a role in the control of arterial sulphated GAG concentration."}
{"id": "PMID:217237", "title": "The effect of ACTH on the arterial blood pressure, heart rate and blood histamine level in rabbits.", "content": "A rapid blood pressure fall, persisting for over one hour, was observed after ACTH injection. The heart rate was initially increased and returned to its basal level within one hour. On the other hand, the level of histamine was significantly increased only in the 60th minute of the experiment. The results obtained showed that a possibility of an indirect ACTH action through an effect of histamine metabolism cannot be excluded.", "contents": "The effect of ACTH on the arterial blood pressure, heart rate and blood histamine level in rabbits. A rapid blood pressure fall, persisting for over one hour, was observed after ACTH injection. The heart rate was initially increased and returned to its basal level within one hour. On the other hand, the level of histamine was significantly increased only in the 60th minute of the experiment. The results obtained showed that a possibility of an indirect ACTH action through an effect of histamine metabolism cannot be excluded."}
{"id": "PMID:217242", "title": "Lack of specific prostaglandin antagonistic effects of 7-oxa-13-prostynoic acid on ovarian metabolism in vitro.", "content": "Prostaglandins (PGs) have been proposed to function as obligatory intermediates in the action of luteinizing hormone (LH) (Kuehl et al. 1970). This based on experiments on isolated mouse ovaries where the substance 7-oxa-13-prostynoic acid (7-oxa-13-PA) was found to block the effect of both PGE1 and LH on ovarian cyclic AMP formation and progesterone synthesis. We have studied whether 7-oxa-13-PA acts as a PG antagonist also on the isolated rat ovary, where PGs of the E type have many effects. Prepubertal rat ovaries were incubated up to 4 h in modified Krebs bicarbonate buffer containing glucose with PGE1 and 7-oxa-13-PA, alone and in combination. PGE1 stimulated the uptake of the non-utilizable amino acids alpha-aminoisobutyric acid (AIB) and cycloleucine in an equally wide dose-range as has earlier been found for the stimulation of lactic acid and cyclic AMP production as well as protein synthesis. 7-oxa-13-PA alone, in concentrations exceeding 25 microgram/ml, stimulated lactic acid production, but inhibited the incorporation of labelled leucine and the uptake of AIB. The uptake of cycloleucine was slightly stimulated. 7-oxa-13-PA did not antagonize the PGE1 effect on lactic acid production. 7-oxa-13-PA diminished the PGE1 effect on the uptake of amino acids and the incorporation into protein, but only in concentrations where it in itself inhibited the protein synthesis. These results show that 7-oxa-13-PA does not act as a PG-antagonist in the prepubertal rat ovary, since it cannot block the effects of PGs without having marked inherent effects.", "contents": "Lack of specific prostaglandin antagonistic effects of 7-oxa-13-prostynoic acid on ovarian metabolism in vitro. Prostaglandins (PGs) have been proposed to function as obligatory intermediates in the action of luteinizing hormone (LH) (Kuehl et al. 1970). This based on experiments on isolated mouse ovaries where the substance 7-oxa-13-prostynoic acid (7-oxa-13-PA) was found to block the effect of both PGE1 and LH on ovarian cyclic AMP formation and progesterone synthesis. We have studied whether 7-oxa-13-PA acts as a PG antagonist also on the isolated rat ovary, where PGs of the E type have many effects. Prepubertal rat ovaries were incubated up to 4 h in modified Krebs bicarbonate buffer containing glucose with PGE1 and 7-oxa-13-PA, alone and in combination. PGE1 stimulated the uptake of the non-utilizable amino acids alpha-aminoisobutyric acid (AIB) and cycloleucine in an equally wide dose-range as has earlier been found for the stimulation of lactic acid and cyclic AMP production as well as protein synthesis. 7-oxa-13-PA alone, in concentrations exceeding 25 microgram/ml, stimulated lactic acid production, but inhibited the incorporation of labelled leucine and the uptake of AIB. The uptake of cycloleucine was slightly stimulated. 7-oxa-13-PA did not antagonize the PGE1 effect on lactic acid production. 7-oxa-13-PA diminished the PGE1 effect on the uptake of amino acids and the incorporation into protein, but only in concentrations where it in itself inhibited the protein synthesis. These results show that 7-oxa-13-PA does not act as a PG-antagonist in the prepubertal rat ovary, since it cannot block the effects of PGs without having marked inherent effects."}
{"id": "PMID:217238", "title": "Effect of vasopressin and oxytocin perfusion of the cerebral ventricles on evoked tongue jerks.", "content": "The effect of increased concentration of vasopressin and oxytocin in the cerebrospinal fluid on the excitability of the hypoglossal nerve nucleus was investigated. The experiments were carried out on rats under chloralose anaesthesia. Retractory jerks of the outstretched tongue were evoked by supra- or infraorbital nerve stimulation during perfusion of the cerebral ventricles with McIlwain-Rodnight solution. The solution contained synthetic arginine vasopressin 0.05 U/ml or synthetic oxytocin 0.05 U/ml. Perfusion of the ventricles with vasopressin increased and perfusion with oxytocin decreased the evoked tongue jerks.", "contents": "Effect of vasopressin and oxytocin perfusion of the cerebral ventricles on evoked tongue jerks. The effect of increased concentration of vasopressin and oxytocin in the cerebrospinal fluid on the excitability of the hypoglossal nerve nucleus was investigated. The experiments were carried out on rats under chloralose anaesthesia. Retractory jerks of the outstretched tongue were evoked by supra- or infraorbital nerve stimulation during perfusion of the cerebral ventricles with McIlwain-Rodnight solution. The solution contained synthetic arginine vasopressin 0.05 U/ml or synthetic oxytocin 0.05 U/ml. Perfusion of the ventricles with vasopressin increased and perfusion with oxytocin decreased the evoked tongue jerks."}
{"id": "PMID:217245", "title": "On the distributive patterns of phosphatases and non-specific esterase and their functional aspects amongst the constituents of the photoreceptors of the Indian Medicinal leech, Poecilobdella granulosa (Savigny, 1822).", "content": "In the present contribution the distributive pattern of phosphatases and non-specific esterase amongst the constituents of the leech eye has been revealed and the significance of the enzymatic locales in relation to the visual processes has been discussed. All the phosphatases studied demonstrate absence of the activity in the lens. Activity of the phosphatases, however, is restricted to the plasma membrane and associated cytoplasm to varying degrees. The significance of the phosphatases in the nerve impulses and transmission has been highlightened. The observation of considerable significance relates the demonstration of a high degree of non-specific esterase activity in the lens, which has defied all the phosphatases. Another observation relates to the positive activity of 5-nucleotidase in the group of axons constituting optic nerve. The significance of this observation has also been discussed.", "contents": "On the distributive patterns of phosphatases and non-specific esterase and their functional aspects amongst the constituents of the photoreceptors of the Indian Medicinal leech, Poecilobdella granulosa (Savigny, 1822). In the present contribution the distributive pattern of phosphatases and non-specific esterase amongst the constituents of the leech eye has been revealed and the significance of the enzymatic locales in relation to the visual processes has been discussed. All the phosphatases studied demonstrate absence of the activity in the lens. Activity of the phosphatases, however, is restricted to the plasma membrane and associated cytoplasm to varying degrees. The significance of the phosphatases in the nerve impulses and transmission has been highlightened. The observation of considerable significance relates the demonstration of a high degree of non-specific esterase activity in the lens, which has defied all the phosphatases. Another observation relates to the positive activity of 5-nucleotidase in the group of axons constituting optic nerve. The significance of this observation has also been discussed."}
{"id": "PMID:217246", "title": "Electroencephalographic investigations in sellar tumours, with special regard to different methods of operative treatment.", "content": "Sixty-six patients with tumours in the sellar region were examined. All were operated on either by the transfrontal or the transsphenoidal route. Pre- and postoperative longitudinal electroencephalographic investigations were performed. Preoperative electroencephalograms showed a normal frequency content in cases of intrasellar tumours or those reaching the chiasma. Nearly all cases had irregularities in the temporal regions. Tumours compressing the third ventricle had slower average frequencies and a general slowing in all cases. Besides these alterations unilateral delta waves or bitemporal dysrhythmic groups were sometimes found. A connection between extension of the tumour and its histological nature could not be found, but the operative approach influenced the electroencephalographic disturbances enormously. After a transfrontal approach and removal of the tumour the electroencephalogram was unchanged. Sometimes a mild transient bitemporal slowing was present. But after a transfrontal operative approach a general slowing was common, usually with focal marked slow activity in the right fronto-temporal area.", "contents": "Electroencephalographic investigations in sellar tumours, with special regard to different methods of operative treatment. Sixty-six patients with tumours in the sellar region were examined. All were operated on either by the transfrontal or the transsphenoidal route. Pre- and postoperative longitudinal electroencephalographic investigations were performed. Preoperative electroencephalograms showed a normal frequency content in cases of intrasellar tumours or those reaching the chiasma. Nearly all cases had irregularities in the temporal regions. Tumours compressing the third ventricle had slower average frequencies and a general slowing in all cases. Besides these alterations unilateral delta waves or bitemporal dysrhythmic groups were sometimes found. A connection between extension of the tumour and its histological nature could not be found, but the operative approach influenced the electroencephalographic disturbances enormously. After a transfrontal approach and removal of the tumour the electroencephalogram was unchanged. Sometimes a mild transient bitemporal slowing was present. But after a transfrontal operative approach a general slowing was common, usually with focal marked slow activity in the right fronto-temporal area."}
{"id": "PMID:217251", "title": "Medical registers.", "content": "Registers are records in which information is precisely noted. Their form owes much to William Farr, who headed the General Register Office in Britain beginning in 1839. Medical registers may be designed for various purposes: preventive medical purposes; specific diseases; treatment, aftercare, and at-risk listings; skills and resources indices; prospective studies; and specific information purposes. Entries are correctly diagnosed consistently updated, and derived from multiple overlapping sources in well-defined populations. In Israel, a national neurologic disease registry was established in 1969 based on the diagnoses of discharge of all hospitalized patients. This registry has yielded valuable epidemiologic information on a large number of neurologic disorders.", "contents": "Medical registers. Registers are records in which information is precisely noted. Their form owes much to William Farr, who headed the General Register Office in Britain beginning in 1839. Medical registers may be designed for various purposes: preventive medical purposes; specific diseases; treatment, aftercare, and at-risk listings; skills and resources indices; prospective studies; and specific information purposes. Entries are correctly diagnosed consistently updated, and derived from multiple overlapping sources in well-defined populations. In Israel, a national neurologic disease registry was established in 1969 based on the diagnoses of discharge of all hospitalized patients. This registry has yielded valuable epidemiologic information on a large number of neurologic disorders."}
{"id": "PMID:217254", "title": "Neurologic complications of diabetes mellitus: transient ischemic attack, stroke, and peripheral neuropathy.", "content": "The incidence of TIA, stroke, and neuropathy was studied in a community-based maturity-onset diabetic population. The frequencies of TIA and stroke were increased in maturity-onset diabetic patients as compared to the population of Rochester, Minnesota. The median age of occurrence of TIA and stroke in diabetics was 74 years, not significantly different from that in non-diabetics. Diabetic patients with hypertension at the time of diagnosis of diabetes mellitus had an increased frequency of TIA and stroke. Control of hypertension and/or diabetes mellitus was associated with a decreased frequency of TIA or stroke. Obesity, clinical coronary heart disease, and an abnormal electrocardiogram at the time of diagnosis of diabetes mellitus were not associated with a significantly increased frequency of TIA or stroke. The most common type of peripheral neuropathy in diabetes mellitus was distal polyneuropathy. Mononeuropathy and autonomic neuropathy were much less frequent. The frequency of distal polyneuropathy increased with the duration of diabetes mellitus. The frequency of neuropathy was increased in patients with poor control, reemphasizing the importance of diabetic control in the prevention of diabetic complications.", "contents": "Neurologic complications of diabetes mellitus: transient ischemic attack, stroke, and peripheral neuropathy. The incidence of TIA, stroke, and neuropathy was studied in a community-based maturity-onset diabetic population. The frequencies of TIA and stroke were increased in maturity-onset diabetic patients as compared to the population of Rochester, Minnesota. The median age of occurrence of TIA and stroke in diabetics was 74 years, not significantly different from that in non-diabetics. Diabetic patients with hypertension at the time of diagnosis of diabetes mellitus had an increased frequency of TIA and stroke. Control of hypertension and/or diabetes mellitus was associated with a decreased frequency of TIA or stroke. Obesity, clinical coronary heart disease, and an abnormal electrocardiogram at the time of diagnosis of diabetes mellitus were not associated with a significantly increased frequency of TIA or stroke. The most common type of peripheral neuropathy in diabetes mellitus was distal polyneuropathy. Mononeuropathy and autonomic neuropathy were much less frequent. The frequency of distal polyneuropathy increased with the duration of diabetes mellitus. The frequency of neuropathy was increased in patients with poor control, reemphasizing the importance of diabetic control in the prevention of diabetic complications."}
{"id": "PMID:217255", "title": "Neurologic complications of acute and chronic renal failure.", "content": "It is obvious from the preceding discussion that neurologic complications contribute significantly to morbidity and mortality in patients with chronic and acute renal failure and that dysfunction of the nervous system continues to occur even in those patients receiving successful renal transplants. In an effort to find the causes of these disorders, a large cooperative study of patients with renal failure will be needed to supply valid and statistically significant data that can be used to test the hypotheses suggested by this and other review papers. At the present time, the data are limited, because in almost all instances small and biased series of patients have been used, and basic criteria of disease have not been standardized. It will be a large task to correct these deficiencies, but it is definitely one that should be undertaken in the near future.", "contents": "Neurologic complications of acute and chronic renal failure. It is obvious from the preceding discussion that neurologic complications contribute significantly to morbidity and mortality in patients with chronic and acute renal failure and that dysfunction of the nervous system continues to occur even in those patients receiving successful renal transplants. In an effort to find the causes of these disorders, a large cooperative study of patients with renal failure will be needed to supply valid and statistically significant data that can be used to test the hypotheses suggested by this and other review papers. At the present time, the data are limited, because in almost all instances small and biased series of patients have been used, and basic criteria of disease have not been standardized. It will be a large task to correct these deficiencies, but it is definitely one that should be undertaken in the near future."}
{"id": "PMID:217257", "title": "Unspecific and specific stimulating effects of 3',5'-cyclic nucleotides (cGMP, cAMP, cIMP, cCMP) on the in vitro biosynthesis of proteochondroitin-4,-6-sulfate and on other anabolic processes from calf rib cartilage.", "content": "With cartilage slices from calf ribs, cGMP as well as cAMP accelerate dose-dependently and specifically label rates of Ch-4-,-6-S protein; they slightly elevate rates of anaerobic glycolysis dose-independently and unspecifically, similar to their 5-monophosphate compounds. cAMP, but not cGMP, slightly stimulates labeling of total protein dose-dependently. Guanosine and adenosine (as well as adenine) accelerate more significantly all three anabolic processes in the order Ch-4-,-6-S protein formation greater than or equal to total protein labeling greater than anaerobic glycolysis. Acceleration of some of the processes rises further after adding theophylline or SQ 20.009, depending on the nucleoside used. diBu-cAMP (but not 8-Br-cAMP) stimulates the three processes more than cAMP; diBu-cGMP and 8-Br-cGMP alone increase the labeling rates of protein more than cGMP, cCMP and cIMP slightly accelerate at least one of the three processes dose-independently and unspecifically, similar to their 5-monophosphate compounds. cUMP was almost inactive. The results point to specific and unspecific effects of cGMP similar or different to those of cAMP.", "contents": "Unspecific and specific stimulating effects of 3',5'-cyclic nucleotides (cGMP, cAMP, cIMP, cCMP) on the in vitro biosynthesis of proteochondroitin-4,-6-sulfate and on other anabolic processes from calf rib cartilage. With cartilage slices from calf ribs, cGMP as well as cAMP accelerate dose-dependently and specifically label rates of Ch-4-,-6-S protein; they slightly elevate rates of anaerobic glycolysis dose-independently and unspecifically, similar to their 5-monophosphate compounds. cAMP, but not cGMP, slightly stimulates labeling of total protein dose-dependently. Guanosine and adenosine (as well as adenine) accelerate more significantly all three anabolic processes in the order Ch-4-,-6-S protein formation greater than or equal to total protein labeling greater than anaerobic glycolysis. Acceleration of some of the processes rises further after adding theophylline or SQ 20.009, depending on the nucleoside used. diBu-cAMP (but not 8-Br-cAMP) stimulates the three processes more than cAMP; diBu-cGMP and 8-Br-cGMP alone increase the labeling rates of protein more than cGMP, cCMP and cIMP slightly accelerate at least one of the three processes dose-independently and unspecifically, similar to their 5-monophosphate compounds. cUMP was almost inactive. The results point to specific and unspecific effects of cGMP similar or different to those of cAMP."}
{"id": "PMID:217261", "title": "Protective action of amiodarone against ventricular fibrillation in the isolated perfused rat heart.", "content": "The pretreatment of rats with amiodarone for 2 minutes to 3 weeks before the excision of their hearts caused a dose-related decrease in heart rate and an increase in the ventricular fibrillation threshold both before and after coronary arterial ligation. Similarly, amiodarone decreased the incidence of ventricular premature extrasystoles, ventricular tachycardia and fibrillation during the period of regional ischemia after coronary arterial ligation and also after reperfusion of the ischemic myocardium. There was no evidence of a metabolic protective effect on ischemic myocardium because tissue high energy phosphate content decreased to a similar extent in ischemic myocardium from control and amiodarone-treated rats. Instead, the protective effect of amiodarone against fibrillation was accompanied by attenuation of the increase in tissue cyclic adenosine monophosphate in ischemic myocardium after coronary arterial ligation. It is proposed that amiodarone exerts a potent antifibrillatory effect by decreasing tissue cyclic adenosine monophosphate in ischemic myocardium.", "contents": "Protective action of amiodarone against ventricular fibrillation in the isolated perfused rat heart. The pretreatment of rats with amiodarone for 2 minutes to 3 weeks before the excision of their hearts caused a dose-related decrease in heart rate and an increase in the ventricular fibrillation threshold both before and after coronary arterial ligation. Similarly, amiodarone decreased the incidence of ventricular premature extrasystoles, ventricular tachycardia and fibrillation during the period of regional ischemia after coronary arterial ligation and also after reperfusion of the ischemic myocardium. There was no evidence of a metabolic protective effect on ischemic myocardium because tissue high energy phosphate content decreased to a similar extent in ischemic myocardium from control and amiodarone-treated rats. Instead, the protective effect of amiodarone against fibrillation was accompanied by attenuation of the increase in tissue cyclic adenosine monophosphate in ischemic myocardium after coronary arterial ligation. It is proposed that amiodarone exerts a potent antifibrillatory effect by decreasing tissue cyclic adenosine monophosphate in ischemic myocardium."}
{"id": "PMID:217262", "title": "Leucocyte function in iron-deficiency anemia.", "content": "Production of hydrogenperoxide and myeloperoxidase-mediated iodination, by leucocytes was studied in normal subjects and subjects suffering from iron-deficiency anemia. The leucocytes obtained from severe cases of iron-deficiency anemia showed decreased myeloperoxidase-mediated iodination. Defective myeloperoxidase-mediated iodination can explain the basis for the leucocyte microbicidal defect in iron deficiency anemia.", "contents": "Leucocyte function in iron-deficiency anemia. Production of hydrogenperoxide and myeloperoxidase-mediated iodination, by leucocytes was studied in normal subjects and subjects suffering from iron-deficiency anemia. The leucocytes obtained from severe cases of iron-deficiency anemia showed decreased myeloperoxidase-mediated iodination. Defective myeloperoxidase-mediated iodination can explain the basis for the leucocyte microbicidal defect in iron deficiency anemia."}
{"id": "PMID:217263", "title": "Scientific advance in acupuncture.", "content": "In this paper we present scientific advance in acupuncture based on electrical, neurophysiological, biochemical and therapeutic studies made inside and outside China since the early fifties. New modalities other than traditional needling techniques notably developed in Japan, France and Germany are described. For future prospects, efforts by making use of systems approach, field-body interaction, self-defense self-strategy and circadian rhythm are likely to produce great fruition in medicine. Possibilities of making advances in \"three P's\" medicine (preventive medicine, precision medicine and people medicine) by acupuncture are discussed.", "contents": "Scientific advance in acupuncture. In this paper we present scientific advance in acupuncture based on electrical, neurophysiological, biochemical and therapeutic studies made inside and outside China since the early fifties. New modalities other than traditional needling techniques notably developed in Japan, France and Germany are described. For future prospects, efforts by making use of systems approach, field-body interaction, self-defense self-strategy and circadian rhythm are likely to produce great fruition in medicine. Possibilities of making advances in \"three P's\" medicine (preventive medicine, precision medicine and people medicine) by acupuncture are discussed."}
{"id": "PMID:217260", "title": "Thymectomy does not affect tumour rejection and cytophilic activity in a murine allogeneic lymphoma model.", "content": "An experimental model was devised in which an AKR lymphoma is conditioned to grow in BALB mice leading to reproducible tumor incidence which makes tumor-bearing (progressor) and tumor-rejecting (regressor) animals simultaneously available. The object of this paper was to determine the effect of neonatal thymectomy (xT) on allogeneic tumor incidence and on anti-tumor cytophilic activity. The latter was determined by the adherence of lymphoma cells to guinea pig peritoneal macrophages previously incubated with preheated mouse serum. The results obtained, in 2-3 month old animals, show no difference in lethal tumor incidence between xT and intact mice, 36% (14/39) vs. 39% (14/36). Neither did xT alter the significant increase in cytophilic antibodies detected in regressor serum, 115 +/- 15 (S.E.) vs. 106+/- 22 0/00 macrophages bearing tumor cells as compared to control values in either xT or normal serum, 53 +/- 3 vs 52 +/- 3. This background cytophilic activity was not significantly altered in progressor serum of either xT or intact mice, 36 +/- 5 vs 65 +/- 6. The specificity of the antitumor cytophilic antibodies was determined by the negative results obtained when a different tumor was used as target cell. It can be concluded that ant-tumor cytophilic antibodies are detectable in regressor but not in progressor serum. Thymectomy in this model does not alter either in vivo tumor incidence or humoral cytophilic activity. Since no thymic remnants were encountered at autopsy, it is postulated that AKR lymphoma cells, which proved to be neoplastic T cells, are capable of rendering T-immunocompetent a thymectomized allogeneic BALB host.", "contents": "Thymectomy does not affect tumour rejection and cytophilic activity in a murine allogeneic lymphoma model. An experimental model was devised in which an AKR lymphoma is conditioned to grow in BALB mice leading to reproducible tumor incidence which makes tumor-bearing (progressor) and tumor-rejecting (regressor) animals simultaneously available. The object of this paper was to determine the effect of neonatal thymectomy (xT) on allogeneic tumor incidence and on anti-tumor cytophilic activity. The latter was determined by the adherence of lymphoma cells to guinea pig peritoneal macrophages previously incubated with preheated mouse serum. The results obtained, in 2-3 month old animals, show no difference in lethal tumor incidence between xT and intact mice, 36% (14/39) vs. 39% (14/36). Neither did xT alter the significant increase in cytophilic antibodies detected in regressor serum, 115 +/- 15 (S.E.) vs. 106+/- 22 0/00 macrophages bearing tumor cells as compared to control values in either xT or normal serum, 53 +/- 3 vs 52 +/- 3. This background cytophilic activity was not significantly altered in progressor serum of either xT or intact mice, 36 +/- 5 vs 65 +/- 6. The specificity of the antitumor cytophilic antibodies was determined by the negative results obtained when a different tumor was used as target cell. It can be concluded that ant-tumor cytophilic antibodies are detectable in regressor but not in progressor serum. Thymectomy in this model does not alter either in vivo tumor incidence or humoral cytophilic activity. Since no thymic remnants were encountered at autopsy, it is postulated that AKR lymphoma cells, which proved to be neoplastic T cells, are capable of rendering T-immunocompetent a thymectomized allogeneic BALB host."}
{"id": "PMID:217264", "title": "Adenosarcoma of the uterus: ultrastructural observations.", "content": "M\u00fcllerian adenosarcoma has been recently described as a distinctive biphasic uterine tumor with benign epithelial and malignant stromal components. The lesion belongs generally to the group of mixed m\u00fcllerian tumors, but the benignity of the epithelium separates it from the other neoplasms of this type. This entity usually affects postmenopausal patients who follow a protracted course. This paper reports a case fulfilling the original clinical and pathologic description of Clement and Scully and adds ultrastructural observations. Electron microscopic examination confirmed the optical impression of a biphasic neoplasm with benign epithelial and malignant stromal components. The epithelium resembled proliferative endometrium, and the stroma had features of endometrial stromal sarcoma or mixed m\u00fcllerian tumor. The findings of stromal resemblance to endometrial stromal sarcoma or mixed m\u00fcllerian tumor and the presence of a variety of m\u00fcllerian epithelia support the proposed m\u00fcllerian derivation of this lesion.", "contents": "Adenosarcoma of the uterus: ultrastructural observations. M\u00fcllerian adenosarcoma has been recently described as a distinctive biphasic uterine tumor with benign epithelial and malignant stromal components. The lesion belongs generally to the group of mixed m\u00fcllerian tumors, but the benignity of the epithelium separates it from the other neoplasms of this type. This entity usually affects postmenopausal patients who follow a protracted course. This paper reports a case fulfilling the original clinical and pathologic description of Clement and Scully and adds ultrastructural observations. Electron microscopic examination confirmed the optical impression of a biphasic neoplasm with benign epithelial and malignant stromal components. The epithelium resembled proliferative endometrium, and the stroma had features of endometrial stromal sarcoma or mixed m\u00fcllerian tumor. The findings of stromal resemblance to endometrial stromal sarcoma or mixed m\u00fcllerian tumor and the presence of a variety of m\u00fcllerian epithelia support the proposed m\u00fcllerian derivation of this lesion."}
{"id": "PMID:217265", "title": "Neuropsychiatric problems in mixed connective tissue disease.", "content": "A group of 20 patients with mixed connective tissue disease, followed for up to five years, was found to have a 55 per cent incidence of neuropsychiatric problems. An aseptic meningitis-like syndrome was the most common presentation and was rapidly responsive to corticosteroid therapy. Other findings were psychosis, convulsions, peripheral neuropathy, trigeminal neuropathy and cerebellar ataxia. An abnormal cerebrospinal fluid was found in five patients; mild pleocytosis, an increased protein content and a first phase colloidal gold curve were the main abnormalities. These neuropsychiatric problems have not been a cause of mortality in this group of patients with mixed connective tissue disease.", "contents": "Neuropsychiatric problems in mixed connective tissue disease. A group of 20 patients with mixed connective tissue disease, followed for up to five years, was found to have a 55 per cent incidence of neuropsychiatric problems. An aseptic meningitis-like syndrome was the most common presentation and was rapidly responsive to corticosteroid therapy. Other findings were psychosis, convulsions, peripheral neuropathy, trigeminal neuropathy and cerebellar ataxia. An abnormal cerebrospinal fluid was found in five patients; mild pleocytosis, an increased protein content and a first phase colloidal gold curve were the main abnormalities. These neuropsychiatric problems have not been a cause of mortality in this group of patients with mixed connective tissue disease."}
{"id": "PMID:217268", "title": "Leukocyte myeloperoxidase deficiency and diabetes mellitus associated with Candida albicans liver abscess.", "content": "Reported here is a case of hereditary myeloperoxidase deficinecy in a diabetic patient suffering from a Candida albicans liver abscess. Peroxidase activity is completely absent from the neutrophils and monocytes although it is present in the eosinophils. The different forms of myeloperoxidase deficiency are discussed.", "contents": "Leukocyte myeloperoxidase deficiency and diabetes mellitus associated with Candida albicans liver abscess. Reported here is a case of hereditary myeloperoxidase deficinecy in a diabetic patient suffering from a Candida albicans liver abscess. Peroxidase activity is completely absent from the neutrophils and monocytes although it is present in the eosinophils. The different forms of myeloperoxidase deficiency are discussed."}
{"id": "PMID:217271", "title": "Influences of an analog of the neuropeptide ACTH 4--9 on mentally retarded adults.", "content": "In a double-blind procedure, 24 mentally retarded adults received 0 mg, 5mg, or 20 mg of an analog of the neuropeptide ACTH 4--9. Following treatment with peptide, the subjects were given the Trails B Test (from the Halstead-Reitan Neuropsychological Battery), the Peabody Picture Vocabulary test, the Benton Visual Retention Test, a concept-formation task, and a standard orienting sequence. The results of the behavioral tests suggested that attentional processes were enhanced in subjects treated with the peptide. The present study, in conjunction with another investigation using the neuropeptide ACTH/MSH 4--10 (Sandman, George, Walker, Nolan & Kastin, 1976), indicates that attentional deficits in mentally retarded adults, traditionally assumed to be irreversible, may be influenced by treatment with fragments of the neuropeptides ACTH and MSH.", "contents": "Influences of an analog of the neuropeptide ACTH 4--9 on mentally retarded adults. In a double-blind procedure, 24 mentally retarded adults received 0 mg, 5mg, or 20 mg of an analog of the neuropeptide ACTH 4--9. Following treatment with peptide, the subjects were given the Trails B Test (from the Halstead-Reitan Neuropsychological Battery), the Peabody Picture Vocabulary test, the Benton Visual Retention Test, a concept-formation task, and a standard orienting sequence. The results of the behavioral tests suggested that attentional processes were enhanced in subjects treated with the peptide. The present study, in conjunction with another investigation using the neuropeptide ACTH/MSH 4--10 (Sandman, George, Walker, Nolan & Kastin, 1976), indicates that attentional deficits in mentally retarded adults, traditionally assumed to be irreversible, may be influenced by treatment with fragments of the neuropeptides ACTH and MSH."}
{"id": "PMID:217269", "title": "Recurrent herpes simplex labialis: viral replication and clinical course.", "content": "The purpose of this study was to provide additional information on the clinical course and viral replication kinetics of herpes simplex virus (HSV) in recurrent herpes labialis. Data were obtained on 20 subjects who were followed for five days from the first day of the lesion. HSV was isolated in 17 subjects (85%); 75% were positive on day 1 of the lesion. Median HSV titer on day 1 was 1.7 x 10(3)/0.2ml. Isolation rates and titers dropped sharply and virus could no longer be detected by day 4. The clinical course both in terms of the frequency and the severity of the symptoms paralleled the kinetics of viral replication. Thermography delineated location of subsequent lesions in three early symptomatic patients who were studied at the time when no visible lesions were observed. These data are felt to provide useful background information for future studies on the efficacy of topical antiviral agents.", "contents": "Recurrent herpes simplex labialis: viral replication and clinical course. The purpose of this study was to provide additional information on the clinical course and viral replication kinetics of herpes simplex virus (HSV) in recurrent herpes labialis. Data were obtained on 20 subjects who were followed for five days from the first day of the lesion. HSV was isolated in 17 subjects (85%); 75% were positive on day 1 of the lesion. Median HSV titer on day 1 was 1.7 x 10(3)/0.2ml. Isolation rates and titers dropped sharply and virus could no longer be detected by day 4. The clinical course both in terms of the frequency and the severity of the symptoms paralleled the kinetics of viral replication. Thermography delineated location of subsequent lesions in three early symptomatic patients who were studied at the time when no visible lesions were observed. These data are felt to provide useful background information for future studies on the efficacy of topical antiviral agents."}
{"id": "PMID:217270", "title": "Infectious mononucleosis and related syndromes.", "content": "The \"mono syndrome\" is an acute febrile disease of older children and young adults which involves the lymphatic system and is characterized hematologically by the presence of 50% or more lymphocytes and monocytes and 10% or more atypical lymphocytes. Epstein-Barr virus (EBV) causes over 90% of the syndrome, cytomegalovirus (CMV) about 5% to 7%, and Toxoplasma gondii less than 1%. Viral hepatitis, adenovirus, rubella, and herpes simplex are rare causes. Only EBV produces classical heterophile-positive infectious mononucleosis. This article reviews the epidemiological and clinical features of this syndrome.", "contents": "Infectious mononucleosis and related syndromes. The \"mono syndrome\" is an acute febrile disease of older children and young adults which involves the lymphatic system and is characterized hematologically by the presence of 50% or more lymphocytes and monocytes and 10% or more atypical lymphocytes. Epstein-Barr virus (EBV) causes over 90% of the syndrome, cytomegalovirus (CMV) about 5% to 7%, and Toxoplasma gondii less than 1%. Viral hepatitis, adenovirus, rubella, and herpes simplex are rare causes. Only EBV produces classical heterophile-positive infectious mononucleosis. This article reviews the epidemiological and clinical features of this syndrome."}
{"id": "PMID:217273", "title": "The hyperlipidemia of pregnancy in normal and complicated pregnancies.", "content": "Alterations in the concentrations of the cholesterol and triglyceride moieties of lipoproteins separated by ultracentrifugation and precipitation methods were studied at frequent intervals throughout pregnancy and the puerperium in a group of 43 women. The plasma cholesterol concentration rose on the average by about 50 per cent, the major increase occurring in the second trimester. The plasma triglyceride concentration rose threefold, reaching its peak during the third trimester. All major lipoproteins participated in these changes: in very-low-density lipoproteins, both lipids rose in proportion to the ratio in nonpregnant women, but in low-density and high-density lipoproteins, the ratio of triglyceride to cholesterol rose. The triglyceride enrighment in low-density lipoproteins reflected the inclusion of intermediate-density lipoproteins (d 1.006 to 1.019). The occurrence of hypertension or pre-eclampsia led to a further increase in lipids in very-low-density lipoproteins. Hypercholesterolemia was greatest in women with pre-existing hypercholesterolemia, and women in the third pregnancy showed higher plasma cholesterol concentrations than women in the first pregnancy. Both cholesterol and triglyceride concentrations decreased significantly within 24 hours of delivery and this was reflected in all lipoproteins. However, while triglyceride levels continued to decrease rapidly returning to nonpregnant levels during the puerperium, cholesterol in low-density lipoprotein remained elevated for at least six to seven weeks post partum.", "contents": "The hyperlipidemia of pregnancy in normal and complicated pregnancies. Alterations in the concentrations of the cholesterol and triglyceride moieties of lipoproteins separated by ultracentrifugation and precipitation methods were studied at frequent intervals throughout pregnancy and the puerperium in a group of 43 women. The plasma cholesterol concentration rose on the average by about 50 per cent, the major increase occurring in the second trimester. The plasma triglyceride concentration rose threefold, reaching its peak during the third trimester. All major lipoproteins participated in these changes: in very-low-density lipoproteins, both lipids rose in proportion to the ratio in nonpregnant women, but in low-density and high-density lipoproteins, the ratio of triglyceride to cholesterol rose. The triglyceride enrighment in low-density lipoproteins reflected the inclusion of intermediate-density lipoproteins (d 1.006 to 1.019). The occurrence of hypertension or pre-eclampsia led to a further increase in lipids in very-low-density lipoproteins. Hypercholesterolemia was greatest in women with pre-existing hypercholesterolemia, and women in the third pregnancy showed higher plasma cholesterol concentrations than women in the first pregnancy. Both cholesterol and triglyceride concentrations decreased significantly within 24 hours of delivery and this was reflected in all lipoproteins. However, while triglyceride levels continued to decrease rapidly returning to nonpregnant levels during the puerperium, cholesterol in low-density lipoprotein remained elevated for at least six to seven weeks post partum."}
{"id": "PMID:217274", "title": "Carpal radiographs in orthodontic treatment.", "content": "The pubescent period offers the best opportunity to accomplish the objectives of orthodontic treatment in the shortest time. Treatment during the period of maximum growth activity reduces some of the uncertainties associated with early treatment. Carpal radiographs can be used as a guide to determine the onset of the adolescent growth spurt and hence provide the clinician with a diagnostic and planning aid to optimize treatment efficiency.", "contents": "Carpal radiographs in orthodontic treatment. The pubescent period offers the best opportunity to accomplish the objectives of orthodontic treatment in the shortest time. Treatment during the period of maximum growth activity reduces some of the uncertainties associated with early treatment. Carpal radiographs can be used as a guide to determine the onset of the adolescent growth spurt and hence provide the clinician with a diagnostic and planning aid to optimize treatment efficiency."}
{"id": "PMID:217276", "title": "Antiphosphaturic action of 25 (OH) vitamin D3 in experimental Fanconi syndrome.", "content": "Renal handling of phosphorus was studied in the following groups of parathyroidectomized rats with maleate-induced Fanconi syndrome: 1) 6 rats receiving intravenous parathyroid hormone, 2) 6 rats receiving intravenous dibutyryl cyclic AMP (DBcAMP), 3) 6 rats undergoing volume expansion with saline, 4) 12 rats receiving intravenous 25 (OH)vitamin D3, 5) 12 rats with acute hypercalcemia induced by intravenous CaCl2, 6) 6 rats with phosphate deprivation, and 7) 6 rats receiving intravenous calcitonin. Parathyroid hormone and calcitonin failed to increase the urinary excretion of both cAMP and phosphorus. Likewise, DBcAMP failed to increase the urinary excretion of phosphorus. Extracellular volume expansion and hypercalcemia (serum calcium 12.9 +/- 0.7 mg/100 ml) did not alter the tubular reabsorption of phosphorus. In phosphate-deprived animals, the fractional excretion 0.16 +/- 0.05 (mean +/- SE) was lower than that in the control animals (maleate-treated without phosphate depletion), 0.46 +/- 0.04 (P less than 0.001). 25 (OH)vitamin D3 decreased the fractional excretion of phosphorus from 0.39 +/- 0.03 in the control (maleate-treated not receiving 25 (OH)vitamin D3) to 0.23 +/- 0.02 (P less than 0.001) in the experimental animals. The present study demonstrated an antiphosphaturic effect of 25(OH)vitamin D3 in experimental Fanconi syndrome; the mechanism of this action is not well understood.", "contents": "Antiphosphaturic action of 25 (OH) vitamin D3 in experimental Fanconi syndrome. Renal handling of phosphorus was studied in the following groups of parathyroidectomized rats with maleate-induced Fanconi syndrome: 1) 6 rats receiving intravenous parathyroid hormone, 2) 6 rats receiving intravenous dibutyryl cyclic AMP (DBcAMP), 3) 6 rats undergoing volume expansion with saline, 4) 12 rats receiving intravenous 25 (OH)vitamin D3, 5) 12 rats with acute hypercalcemia induced by intravenous CaCl2, 6) 6 rats with phosphate deprivation, and 7) 6 rats receiving intravenous calcitonin. Parathyroid hormone and calcitonin failed to increase the urinary excretion of both cAMP and phosphorus. Likewise, DBcAMP failed to increase the urinary excretion of phosphorus. Extracellular volume expansion and hypercalcemia (serum calcium 12.9 +/- 0.7 mg/100 ml) did not alter the tubular reabsorption of phosphorus. In phosphate-deprived animals, the fractional excretion 0.16 +/- 0.05 (mean +/- SE) was lower than that in the control animals (maleate-treated without phosphate depletion), 0.46 +/- 0.04 (P less than 0.001). 25 (OH)vitamin D3 decreased the fractional excretion of phosphorus from 0.39 +/- 0.03 in the control (maleate-treated not receiving 25 (OH)vitamin D3) to 0.23 +/- 0.02 (P less than 0.001) in the experimental animals. The present study demonstrated an antiphosphaturic effect of 25(OH)vitamin D3 in experimental Fanconi syndrome; the mechanism of this action is not well understood."}
{"id": "PMID:217277", "title": "Relationship between PAH transport and Na-K-ATPase activity in the rabbit kidney.", "content": "The relationship between Na-K-ATPase activity and p-aminohippurate (PAH) transport was examined in renal cortical slices of mixed-breed rabbits by using ouabain to vary the level of Na-K-ATPase activity. Ouabain increased passive PAH uptake, measured in the presence of probenecid. Slice homogenate Na-K-ATPase activity was inhibited by 50% with about 2 X 10(-6) M ouabain. When the concentration was 10(-5) M or above, active PAH uptake was inhibited. Lower concentrations (10(-7) and 10(-6) M) of ouabain stimulated active PAH uptake. Acetate stimulated PAH uptake when medium ouabain was less than 10(-4) M. Ouabain, 10(-5) M and higher, caused intracellular K+ to fall and Na+ to rise. The changes in active PAH uptake observed with ouabain correlated much better with changes in intracellular K+ or Na+ levels (P less than 0.01) than with changes in slice homogenate Na-K-ATPase activity. Vmax for active PAH uptake decreased with 5 X 10(-5) M ouabain, and tended to increase with 10(-7) M ouabain. Ouabain did not alter Km for active PAH uptake. The data support the hypothesis that there is a functional link between active PAH transport and Na-K-ATPase activity. This linkage may be an indirect one mediated by changes in intracellular cation concentrations.", "contents": "Relationship between PAH transport and Na-K-ATPase activity in the rabbit kidney. The relationship between Na-K-ATPase activity and p-aminohippurate (PAH) transport was examined in renal cortical slices of mixed-breed rabbits by using ouabain to vary the level of Na-K-ATPase activity. Ouabain increased passive PAH uptake, measured in the presence of probenecid. Slice homogenate Na-K-ATPase activity was inhibited by 50% with about 2 X 10(-6) M ouabain. When the concentration was 10(-5) M or above, active PAH uptake was inhibited. Lower concentrations (10(-7) and 10(-6) M) of ouabain stimulated active PAH uptake. Acetate stimulated PAH uptake when medium ouabain was less than 10(-4) M. Ouabain, 10(-5) M and higher, caused intracellular K+ to fall and Na+ to rise. The changes in active PAH uptake observed with ouabain correlated much better with changes in intracellular K+ or Na+ levels (P less than 0.01) than with changes in slice homogenate Na-K-ATPase activity. Vmax for active PAH uptake decreased with 5 X 10(-5) M ouabain, and tended to increase with 10(-7) M ouabain. Ouabain did not alter Km for active PAH uptake. The data support the hypothesis that there is a functional link between active PAH transport and Na-K-ATPase activity. This linkage may be an indirect one mediated by changes in intracellular cation concentrations."}
{"id": "PMID:217278", "title": "Modulation of adrenergic transmission by angiotensins in the perfused rat mesentery.", "content": "Isolated rat mesenteric arteries perfused with a modified Krebs solution were utilized to study the effects of angiotensin II (AII), angiotensin III (AIII), and [des-Asp1-Arg2]AII on adrenergic transmission. Angiotensin II potentiated vasoconstrictor responses to both sympathetic nerve stimulation and to exogenous norepinephrine, whereas AIII and [des-Asp1-Arg2]AII potentiated vasoconstrictor responses to exogenous norepinephrine only. When the responses to exogenous norepinephrine were compared, the order of agonist potency was AIII greater than AII greater than [des-Asp1-Arg2]AII. The potentiation of sympathetic nerve stimulation by AII was inhibited by simultaneous administration of AIII (25%), [des-Asp1-Arg2]AII (51%), [Sar1-Ile8]AII (83%), and (Ile7)AIII (80%). The potentiation of exogenous norepinephrine by AII, AIII, and [des-Asp1-Arg2]AII was inhibited by [Sar1-Ile8]AII (110%, 113%, and 108%, respectively) and by [Ile7]AIII (50%, 64%, 91%, respectively). We conclude that AII possesses the capacity both to increase norpinephrine release during sympathetic nerve stimulation and to decrease norepinephrine reuptake, whereas AIII and [des-Asp1-Arg2]AII decrease norepinephrine release and reuptake. Also, under conditions of increased N-terminal degradation of AII, blockade of norepinephrine reuptake would be increased while the release of norepinephrine by nerve stimulation would be reduced.", "contents": "Modulation of adrenergic transmission by angiotensins in the perfused rat mesentery. Isolated rat mesenteric arteries perfused with a modified Krebs solution were utilized to study the effects of angiotensin II (AII), angiotensin III (AIII), and [des-Asp1-Arg2]AII on adrenergic transmission. Angiotensin II potentiated vasoconstrictor responses to both sympathetic nerve stimulation and to exogenous norepinephrine, whereas AIII and [des-Asp1-Arg2]AII potentiated vasoconstrictor responses to exogenous norepinephrine only. When the responses to exogenous norepinephrine were compared, the order of agonist potency was AIII greater than AII greater than [des-Asp1-Arg2]AII. The potentiation of sympathetic nerve stimulation by AII was inhibited by simultaneous administration of AIII (25%), [des-Asp1-Arg2]AII (51%), [Sar1-Ile8]AII (83%), and (Ile7)AIII (80%). The potentiation of exogenous norepinephrine by AII, AIII, and [des-Asp1-Arg2]AII was inhibited by [Sar1-Ile8]AII (110%, 113%, and 108%, respectively) and by [Ile7]AIII (50%, 64%, 91%, respectively). We conclude that AII possesses the capacity both to increase norpinephrine release during sympathetic nerve stimulation and to decrease norepinephrine reuptake, whereas AIII and [des-Asp1-Arg2]AII decrease norepinephrine release and reuptake. Also, under conditions of increased N-terminal degradation of AII, blockade of norepinephrine reuptake would be increased while the release of norepinephrine by nerve stimulation would be reduced."}
{"id": "PMID:217279", "title": "Development and regression of exercise-induced cardiac hypertrophy in rats.", "content": "Adult female rats were exercised by daily swimming. All the increase in heart weight induced by the exercise occurred within 14 days and averaged 30%. The half times of the increases in heart weight and total protein content were about 4.5 days, whereas that of cytochrome c, which was used as a mitochondrial marker, was 6.5 days. The total amounts of DNA and of hydroxyproline in the heart, which were used to evaluate the degree of connective tissue hyperplasia, increased only slightly (8% and 10%, respectively). Other animals were subjected to the same swimming program for 21 days. Groups of rats were killed at various time intervals after stopping exercise. Heart weight, total protein content, and total cytochrome c content decreased rapidly initially, with 60% of the total regression of hypertrophy occurring during the first week. Thereafter, heart weight fell more gradually toward the sedentary control value. The hydroxyproline content of the heart, which was increased 10%, did not decrease during the regression of the hypertrophy.", "contents": "Development and regression of exercise-induced cardiac hypertrophy in rats. Adult female rats were exercised by daily swimming. All the increase in heart weight induced by the exercise occurred within 14 days and averaged 30%. The half times of the increases in heart weight and total protein content were about 4.5 days, whereas that of cytochrome c, which was used as a mitochondrial marker, was 6.5 days. The total amounts of DNA and of hydroxyproline in the heart, which were used to evaluate the degree of connective tissue hyperplasia, increased only slightly (8% and 10%, respectively). Other animals were subjected to the same swimming program for 21 days. Groups of rats were killed at various time intervals after stopping exercise. Heart weight, total protein content, and total cytochrome c content decreased rapidly initially, with 60% of the total regression of hypertrophy occurring during the first week. Thereafter, heart weight fell more gradually toward the sedentary control value. The hydroxyproline content of the heart, which was increased 10%, did not decrease during the regression of the hypertrophy."}
{"id": "PMID:217281", "title": "Swine influenza vaccine program in the community: acceptability, reactions and responses.", "content": "The operation of the national swine influenza immunization program was observed in the community of Tecumseh, Michigan. The purpose was to determine acceptability of a parenteral vaccine intended for the general population. Participation of the residents was excellent. More than 64 per cent of eligibles were vaccinated; this figure resembled that of the rest of the local area, but not the national figures nor a suburban area of Michigan where a similar study was carried out. Sore arm after vaccination was reported most frequently in younger female participants; however, sore arm was accepted as part of the process of vaccination and not considered a reaction by most. Such perceived reactions were not as commonly reported as in the large suburban area. Antibody response to the vaccine was excellent, not only in terms of antibodies to the swine virus itself but also in terms of cross reactive antibodies to the emergent H1N1 (Russian) influenza strain. As a result of the program, many vaccine recipients in the 25 to 49 year age groups are protected against this new epidemic virus.", "contents": "Swine influenza vaccine program in the community: acceptability, reactions and responses. The operation of the national swine influenza immunization program was observed in the community of Tecumseh, Michigan. The purpose was to determine acceptability of a parenteral vaccine intended for the general population. Participation of the residents was excellent. More than 64 per cent of eligibles were vaccinated; this figure resembled that of the rest of the local area, but not the national figures nor a suburban area of Michigan where a similar study was carried out. Sore arm after vaccination was reported most frequently in younger female participants; however, sore arm was accepted as part of the process of vaccination and not considered a reaction by most. Such perceived reactions were not as commonly reported as in the large suburban area. Antibody response to the vaccine was excellent, not only in terms of antibodies to the swine virus itself but also in terms of cross reactive antibodies to the emergent H1N1 (Russian) influenza strain. As a result of the program, many vaccine recipients in the 25 to 49 year age groups are protected against this new epidemic virus."}
{"id": "PMID:217283", "title": "Ultrastructural changes in the rat metrial gland in the latter half of pregnancy.", "content": "The ultrastructural changes occurring in the metrial gland in the latter half of pregnancy in the rat have been studied. Typical palely stained granulated cells are present in the metrial gland up to day 20 but many granulated cells show variations in appearance which may be associated with degeneration. In some the cytoplasm is more darkly stained and such cells often have apparently empty areas of cytoplasm adjacent to the granules. From day 14 onwards many areas of the gland show cellular debris, apparently resulting from lysis of the granulated cells. However, occasionally normal granulated cells are present in blood vessels and have been observed apparently penetrating the vascular endothelium. A variety of changes was also noted in the stromal cell population. Inclusions became apparent in many of these cells; some of these consisted of lipid while others resembled granules from the typical granulated cells. Other cells with numerous inclusions appeared to be macrophages. Lysis of granulated cells in situ is compatible with suggestions that the metrial gland produces a holocrine secretion, though some normal granulated cells enter blood vessels. The stromal cells may have a phagocytic role in late pregnancy but evidence for this was inconclusive.", "contents": "Ultrastructural changes in the rat metrial gland in the latter half of pregnancy. The ultrastructural changes occurring in the metrial gland in the latter half of pregnancy in the rat have been studied. Typical palely stained granulated cells are present in the metrial gland up to day 20 but many granulated cells show variations in appearance which may be associated with degeneration. In some the cytoplasm is more darkly stained and such cells often have apparently empty areas of cytoplasm adjacent to the granules. From day 14 onwards many areas of the gland show cellular debris, apparently resulting from lysis of the granulated cells. However, occasionally normal granulated cells are present in blood vessels and have been observed apparently penetrating the vascular endothelium. A variety of changes was also noted in the stromal cell population. Inclusions became apparent in many of these cells; some of these consisted of lipid while others resembled granules from the typical granulated cells. Other cells with numerous inclusions appeared to be macrophages. Lysis of granulated cells in situ is compatible with suggestions that the metrial gland produces a holocrine secretion, though some normal granulated cells enter blood vessels. The stromal cells may have a phagocytic role in late pregnancy but evidence for this was inconclusive."}
{"id": "PMID:217286", "title": "Susceptibility to rhinovirus infection in chronic bronchitis.", "content": "The role of rhinoviruses in chronic bronchitis was examined serologically in the community of Tecumseh, Michigan. Five different rhinovirus types had been identified by isolation to be present in the community during the time of the study. They were tested against serums obtained from persons with chronic bronchitis and matched control subjects. Both males and females with chronic bronchitis had more frequent infections than did the control subjects; for males, the differences were significant. The higher infection rate among the bronchitic subjects was not related to their being deficient in antibody at the start of the study. It was concluded that persons with chronic bronchitis appear to be more susceptible to rhinovirus infection, as they are to other viral pathogens.", "contents": "Susceptibility to rhinovirus infection in chronic bronchitis. The role of rhinoviruses in chronic bronchitis was examined serologically in the community of Tecumseh, Michigan. Five different rhinovirus types had been identified by isolation to be present in the community during the time of the study. They were tested against serums obtained from persons with chronic bronchitis and matched control subjects. Both males and females with chronic bronchitis had more frequent infections than did the control subjects; for males, the differences were significant. The higher infection rate among the bronchitic subjects was not related to their being deficient in antibody at the start of the study. It was concluded that persons with chronic bronchitis appear to be more susceptible to rhinovirus infection, as they are to other viral pathogens."}
{"id": "PMID:217287", "title": "Phosphatidate phosphohydrolase activity in porcine pulmonary surfactant.", "content": "The composition and enzymatic activity of porcine surfactant obtained by lung lavage was examined. The ratio of phospholipid to protein was found to be 13 mg per mg. Phosphatidate phosphohydrolase (PAPase) activity was present in lavage surfactant, lamellar bodies isolated from porcine lung tissue, and lamellar bodies isolated from human amniotic fluid. The optimal pH of PAPase in surfactant in lamellar bodies was 6.0. Cholinephosphotransferase activity was also present gradient centrifugation of amniotic fluid, the highest PAPase specific activity was found in the fraction that banded at the 0.65 M sucrose interface, similar to lamellar bodies obtained from porcine lung. From these results, we conclude that the enzyme PAPase remains closely associated with the surface active lipids during the process of storage and secretion of surfactant.", "contents": "Phosphatidate phosphohydrolase activity in porcine pulmonary surfactant. The composition and enzymatic activity of porcine surfactant obtained by lung lavage was examined. The ratio of phospholipid to protein was found to be 13 mg per mg. Phosphatidate phosphohydrolase (PAPase) activity was present in lavage surfactant, lamellar bodies isolated from porcine lung tissue, and lamellar bodies isolated from human amniotic fluid. The optimal pH of PAPase in surfactant in lamellar bodies was 6.0. Cholinephosphotransferase activity was also present gradient centrifugation of amniotic fluid, the highest PAPase specific activity was found in the fraction that banded at the 0.65 M sucrose interface, similar to lamellar bodies obtained from porcine lung. From these results, we conclude that the enzyme PAPase remains closely associated with the surface active lipids during the process of storage and secretion of surfactant."}
{"id": "PMID:217288", "title": "Regulation of airway smooth muscle tone in sleeping dogs.", "content": "We examined the influence of sleep state on airway smooth muscle tone in 4 unanesthetized dogs that were trained to sleep in the laboratory. The dogs had been prepared with a permanent side-hole tracheostomy and bilateral cervical vagal loops. During the studies, the dogs breathed through a cuffed endotracheal tube inserted through the tracheostomy. To monitor changes in tracheal smooth muscle tone, we measured the pressure in the water-filled cuff of the endotracheal tube. The technique was validated by examining changes in cuff pressure after administration to the dogs of a series of chemical agents and physiologic stimuli known to constrict or relax tracheobronchial smooth muscle. Sleep state of the dogs was determined by behavioral, electroencephalographic, and electromyographic criteria. During quiet wakefulness, tracheal smooth muscle tone was stable. With the onset and progression of sleep through the nonrapid-eye movement stages, airway smooth muscle tone relaxed (decrease in cuff pressure of 20 to 40 cm H2O), reaching a new steady level during slow-wave sleep. In contrast, during rapid-eye-movement sleep, tracheal smooth muscle tone fluctuated markedly and erratically, as reflected by changes in cuff pressure as large as 90 cm H2O. Partial blockade of the vagus nerves, by cooling the exteriorized cervical vagal loops, decreased or abolished the fluctuations in tracheal smooth muscle tone during rapid-eye-movement sleep at temperatures that did not abolish resting tone, demonstrating that the changes in tone during rapid-eye-movement sleep were related to variability in neural control of airway smooth muscle.", "contents": "Regulation of airway smooth muscle tone in sleeping dogs. We examined the influence of sleep state on airway smooth muscle tone in 4 unanesthetized dogs that were trained to sleep in the laboratory. The dogs had been prepared with a permanent side-hole tracheostomy and bilateral cervical vagal loops. During the studies, the dogs breathed through a cuffed endotracheal tube inserted through the tracheostomy. To monitor changes in tracheal smooth muscle tone, we measured the pressure in the water-filled cuff of the endotracheal tube. The technique was validated by examining changes in cuff pressure after administration to the dogs of a series of chemical agents and physiologic stimuli known to constrict or relax tracheobronchial smooth muscle. Sleep state of the dogs was determined by behavioral, electroencephalographic, and electromyographic criteria. During quiet wakefulness, tracheal smooth muscle tone was stable. With the onset and progression of sleep through the nonrapid-eye movement stages, airway smooth muscle tone relaxed (decrease in cuff pressure of 20 to 40 cm H2O), reaching a new steady level during slow-wave sleep. In contrast, during rapid-eye-movement sleep, tracheal smooth muscle tone fluctuated markedly and erratically, as reflected by changes in cuff pressure as large as 90 cm H2O. Partial blockade of the vagus nerves, by cooling the exteriorized cervical vagal loops, decreased or abolished the fluctuations in tracheal smooth muscle tone during rapid-eye-movement sleep at temperatures that did not abolish resting tone, demonstrating that the changes in tone during rapid-eye-movement sleep were related to variability in neural control of airway smooth muscle."}
{"id": "PMID:217289", "title": "Oral angiotensin-converting enzyme inhibitor in long-term treatment of hypertensive patients.", "content": "The antihypertensive effect of the orally active angiotensin-converting enzyme inhibitor captopril (SQ 14225) was assessed in 22 hypertensive patients of whom 17 were followed for periods ranging from 1 to 7 months. Of these, eight had essential hypertension, eight had renovascular hypertension, and six had hypertension associated with chronic renal failure. Blood pressure decreased markedly in all patients, including those with low renin levels. Nevertheless, the magnitude of blood pressure reduction correlated with the base-line plasma renin activity (r = 0.58, P less than 0.01). Increasing the dose of captopril from 25 to 200 mg did not enhance the amplitude of the antihypertensive effect but did increase its duration. Patients' blood pressure remained well controlled and free of side-effects with a maximal daily dose of up to 200 mg by mouth twice daily. Despite the blood pressure reduction, sodium excretion tended to increase, probably because of reduced aldosterone secretion. There was no evidence of orthostatic hypotension, and no escape from the antihypertensive effect was observed. These results indicate that chronic inhibition of the angiotensin-converting enzyme with an orally active compound offers a new, efficient, and well-tolerated approach to the treatment of hypertension.", "contents": "Oral angiotensin-converting enzyme inhibitor in long-term treatment of hypertensive patients. The antihypertensive effect of the orally active angiotensin-converting enzyme inhibitor captopril (SQ 14225) was assessed in 22 hypertensive patients of whom 17 were followed for periods ranging from 1 to 7 months. Of these, eight had essential hypertension, eight had renovascular hypertension, and six had hypertension associated with chronic renal failure. Blood pressure decreased markedly in all patients, including those with low renin levels. Nevertheless, the magnitude of blood pressure reduction correlated with the base-line plasma renin activity (r = 0.58, P less than 0.01). Increasing the dose of captopril from 25 to 200 mg did not enhance the amplitude of the antihypertensive effect but did increase its duration. Patients' blood pressure remained well controlled and free of side-effects with a maximal daily dose of up to 200 mg by mouth twice daily. Despite the blood pressure reduction, sodium excretion tended to increase, probably because of reduced aldosterone secretion. There was no evidence of orthostatic hypotension, and no escape from the antihypertensive effect was observed. These results indicate that chronic inhibition of the angiotensin-converting enzyme with an orally active compound offers a new, efficient, and well-tolerated approach to the treatment of hypertension."}
{"id": "PMID:217290", "title": "Cholesterol in the prediction of atherosclerotic disease. New perspectives based on the Framingham study.", "content": "Prospective data at Framingham and elsewhere have shown conclusively that risk of coronary heart disease in persons younger than age 50 is strikingly related to the serum total cholesterol level. Within so-called normal limits risk has been found to mount over a five-fold range. The impact has been found to be augmented by other risk factors. The contribution of the serum total cholesterol to risk has also been found to be determined by its partition in the various lipoprotein fractions. A relatively large amount of cholesterol in the low-density lipoprotein fraction is atherogenic, whereas that in the high-density fraction appears protective. The independent contribution of very-low density lipoprotein and its triglyceride or cholesterol content has, on the other hand, not been established. The previous position that virtually all of the lipid information pertaining to coronary heart disease resided in the serum total cholesterol must be accordingly modified.", "contents": "Cholesterol in the prediction of atherosclerotic disease. New perspectives based on the Framingham study. Prospective data at Framingham and elsewhere have shown conclusively that risk of coronary heart disease in persons younger than age 50 is strikingly related to the serum total cholesterol level. Within so-called normal limits risk has been found to mount over a five-fold range. The impact has been found to be augmented by other risk factors. The contribution of the serum total cholesterol to risk has also been found to be determined by its partition in the various lipoprotein fractions. A relatively large amount of cholesterol in the low-density lipoprotein fraction is atherogenic, whereas that in the high-density fraction appears protective. The independent contribution of very-low density lipoprotein and its triglyceride or cholesterol content has, on the other hand, not been established. The previous position that virtually all of the lipid information pertaining to coronary heart disease resided in the serum total cholesterol must be accordingly modified."}
{"id": "PMID:217293", "title": "Opiate receptors: some anatomical and physiological aspects.", "content": "It is possible to localize opiate receptors by light microscopic autoradiography using techniques developed for the autoradiographic localization of small diffusible molecules. The receptors are found in the neuropil of anatomical areas associated with various physiologic functions known to be altered by opiates. In some areas, opiate receptors are associated with the axons of small diameter fibers. Many kinds of studies, especially electrophysiologic studies, provide evidence that receptors revealed in these studies have a physiological function. Electrophysiological and immunohistochemical studies of the enkephalins provide results which are compatible with the notion that the enkephalins are the endogenous substrates of the opiate receptors.", "contents": "Opiate receptors: some anatomical and physiological aspects. It is possible to localize opiate receptors by light microscopic autoradiography using techniques developed for the autoradiographic localization of small diffusible molecules. The receptors are found in the neuropil of anatomical areas associated with various physiologic functions known to be altered by opiates. In some areas, opiate receptors are associated with the axons of small diameter fibers. Many kinds of studies, especially electrophysiologic studies, provide evidence that receptors revealed in these studies have a physiological function. Electrophysiological and immunohistochemical studies of the enkephalins provide results which are compatible with the notion that the enkephalins are the endogenous substrates of the opiate receptors."}
{"id": "PMID:217295", "title": "Pretracheal cervical granular cell myoblastoma.", "content": "This case report deals with a solitary granular cell myoblastoma extrinsic to the proximal trachea. This lesion can be encountered frequently by the plastic surgeon; its histology, incidence and treatment are reviewed here. It is important to reemphasize that local extirpation is appropriate treatment of what is almost always a benign neoplasm, and intraoperative pathological diagnosis guides the surgeon in providing curative therapy.", "contents": "Pretracheal cervical granular cell myoblastoma. This case report deals with a solitary granular cell myoblastoma extrinsic to the proximal trachea. This lesion can be encountered frequently by the plastic surgeon; its histology, incidence and treatment are reviewed here. It is important to reemphasize that local extirpation is appropriate treatment of what is almost always a benign neoplasm, and intraoperative pathological diagnosis guides the surgeon in providing curative therapy."}
{"id": "PMID:217298", "title": "Juvenile amaurotic idiocy (neuronal ceroid lipofuscinosis) and lymphocyte fingerprint profiles.", "content": "Lymphocytes from 3 children with a form of juvenile amaurotic idiocy (characterized by retinal blindness, progressive dementia, and extrapyramidal motor disturbance) were studied by electron microscopy. Numerous fingerprint profiles (FP) were found in vacuolated lymphocytes from all 3 patients and an asymptomatic younger sibling of 1 patient who subsequently became symptomatic. We propose that the combination of this clinical picture and vacuolated lymphocytes with FP is sufficiently distinctive for clinical and research purposes until the biochemical defect is discovered. Wider utilization of ultrastructural study of lymphocytes should increase the number of children diagnosed and allow detection of asymptomatic patients.", "contents": "Juvenile amaurotic idiocy (neuronal ceroid lipofuscinosis) and lymphocyte fingerprint profiles. Lymphocytes from 3 children with a form of juvenile amaurotic idiocy (characterized by retinal blindness, progressive dementia, and extrapyramidal motor disturbance) were studied by electron microscopy. Numerous fingerprint profiles (FP) were found in vacuolated lymphocytes from all 3 patients and an asymptomatic younger sibling of 1 patient who subsequently became symptomatic. We propose that the combination of this clinical picture and vacuolated lymphocytes with FP is sufficiently distinctive for clinical and research purposes until the biochemical defect is discovered. Wider utilization of ultrastructural study of lymphocytes should increase the number of children diagnosed and allow detection of asymptomatic patients."}
{"id": "PMID:217299", "title": "Neurological manifestations of Fabry disease in female carriers.", "content": "A family is described in which a 33-year-old man has classic X-linked recessive Fabry disease. His 2 sisters were discovered to be heterozygous carriers of the Fabry gene and to have both episodic and permanent neurological deficits including vertigo, tinnitus, long tract motor signs, and bladder incontinence. The most concise explanation for these findings is that the sisters manifest central nervous system complications of the Fabry carrier state. This family provides additional evidence that female carriers of rare X-linked recessive disorders may exhibit serious consequences of the disease, presumably related to tissue variability in expression of mutant enzyme activity.", "contents": "Neurological manifestations of Fabry disease in female carriers. A family is described in which a 33-year-old man has classic X-linked recessive Fabry disease. His 2 sisters were discovered to be heterozygous carriers of the Fabry gene and to have both episodic and permanent neurological deficits including vertigo, tinnitus, long tract motor signs, and bladder incontinence. The most concise explanation for these findings is that the sisters manifest central nervous system complications of the Fabry carrier state. This family provides additional evidence that female carriers of rare X-linked recessive disorders may exhibit serious consequences of the disease, presumably related to tissue variability in expression of mutant enzyme activity."}
{"id": "PMID:217300", "title": "Treatment of experimental herpesvirus infections with phosphonoformate and some comparisons with phosphonoacetate.", "content": "Phosphonoformate (PF) at a concentration of 5 to 10 mug/ml inhibited the growth of type 1 strains of herpes simplex virus (HSV) in tissue culture, whereas 20 to 30 mug/ml was required for inhibition of type 2 strains and about 50 mug/ml was required for murine cytomegalovirus. In mice inoculated intraperitoneally or intracerebrally with HSV or intraperitoneally with murine cytomegalovirus, treatment with 250 to 400 mg of PF per kg twice daily for 5 days had only minimal effectiveness. When mice were inoculated intravaginally (i.vg.) with HSV type 2 and treated i.vg. with 10% PF beginning 3 h after viral inoculation, treatment was effective in completely inhibiting viral replication in the genital tract. If i.vg. therapy was initiated 24 h after infection, when the mice had a mean virus titer of 10(5) plaque-forming units in vaginal secretions, a significant reduction in the mean virus titer was observed on days 3, 5, and 7 after infection as compared with control animals. In guinea pigs treated i.vg. with 10% PF beginning 6 h after i.vg. inoculation with HSV type 2 there was also complete inhibition of viral replication in the genital tract, and no extenal lesions developed. When therapy was initiated 24 h after infection there was a 4 to 5-log decrease in viral titers on days 3, 5, and 7 of the infection and a slight delay in the development of external lesions.", "contents": "Treatment of experimental herpesvirus infections with phosphonoformate and some comparisons with phosphonoacetate. Phosphonoformate (PF) at a concentration of 5 to 10 mug/ml inhibited the growth of type 1 strains of herpes simplex virus (HSV) in tissue culture, whereas 20 to 30 mug/ml was required for inhibition of type 2 strains and about 50 mug/ml was required for murine cytomegalovirus. In mice inoculated intraperitoneally or intracerebrally with HSV or intraperitoneally with murine cytomegalovirus, treatment with 250 to 400 mg of PF per kg twice daily for 5 days had only minimal effectiveness. When mice were inoculated intravaginally (i.vg.) with HSV type 2 and treated i.vg. with 10% PF beginning 3 h after viral inoculation, treatment was effective in completely inhibiting viral replication in the genital tract. If i.vg. therapy was initiated 24 h after infection, when the mice had a mean virus titer of 10(5) plaque-forming units in vaginal secretions, a significant reduction in the mean virus titer was observed on days 3, 5, and 7 after infection as compared with control animals. In guinea pigs treated i.vg. with 10% PF beginning 6 h after i.vg. inoculation with HSV type 2 there was also complete inhibition of viral replication in the genital tract, and no extenal lesions developed. When therapy was initiated 24 h after infection there was a 4 to 5-log decrease in viral titers on days 3, 5, and 7 of the infection and a slight delay in the development of external lesions."}
{"id": "PMID:217297", "title": "Efficacy of sodium diethyldithiocarbamate (dithiocarb) in acute nickel carbonyl poisoning.", "content": "A brief historical resume is presented on the use of dithiocarbamates for the treatment of persons exposed to nickel carbonyl. The specificity of the treatment is demonstrated in an industrial accident in which four men were simultaneously exposed to nickel carbonyl vapors. Three of the men received dithiocarb within 24 hours after exposure and the fourth was hospitalized by his family physician and treated for bronchopneumonia with antibiotics and without benefit of dithiocarb. The three workmen who received dithiocarb became symptomless and returned to work within 72 hours after exposure. The fourth man who had not received dithiocarb died within five days after exposure.", "contents": "Efficacy of sodium diethyldithiocarbamate (dithiocarb) in acute nickel carbonyl poisoning. A brief historical resume is presented on the use of dithiocarbamates for the treatment of persons exposed to nickel carbonyl. The specificity of the treatment is demonstrated in an industrial accident in which four men were simultaneously exposed to nickel carbonyl vapors. Three of the men received dithiocarb within 24 hours after exposure and the fourth was hospitalized by his family physician and treated for bronchopneumonia with antibiotics and without benefit of dithiocarb. The three workmen who received dithiocarb became symptomless and returned to work within 72 hours after exposure. The fourth man who had not received dithiocarb died within five days after exposure."}
{"id": "PMID:217301", "title": "Effect of 9-(2-hydroxyethoxymethyl)guanine on herpesvirus-induced keratitis and iritis in rabbits.", "content": "Drugs used for the inhibition of DNA viruses, such as iododeoxyuridine, adenine arabinoside, or trifluorothymidine, are not biochemically selective in their action and also interfere with normal cellular functions. The recently reported 9-(2-hydroxyethoxymethyl)guanine (acycloguanosine) is selectively phosphorylated by viral thymidine kinase but not by normal cellular thymidine kinase. Our present studies show that the acycloguanosine is as effective in treating herpetic keratitis in the rabbit as iododeoxyuridine and trifluorothymidine when given topically as an ointment. It is also effective when given intravenously for the treatment of herpetic iritis and is effective in preventing death from encephalitis in rabbits.", "contents": "Effect of 9-(2-hydroxyethoxymethyl)guanine on herpesvirus-induced keratitis and iritis in rabbits. Drugs used for the inhibition of DNA viruses, such as iododeoxyuridine, adenine arabinoside, or trifluorothymidine, are not biochemically selective in their action and also interfere with normal cellular functions. The recently reported 9-(2-hydroxyethoxymethyl)guanine (acycloguanosine) is selectively phosphorylated by viral thymidine kinase but not by normal cellular thymidine kinase. Our present studies show that the acycloguanosine is as effective in treating herpetic keratitis in the rabbit as iododeoxyuridine and trifluorothymidine when given topically as an ointment. It is also effective when given intravenously for the treatment of herpetic iritis and is effective in preventing death from encephalitis in rabbits."}
{"id": "PMID:217302", "title": "Comparative study of ten bacteriocins of Clostridium perfringens.", "content": "Bacteriocins of Clostridium perfringens were prepared by ammonium sulfate precipitation of supernatant broth from 10 bacteriocinogenic strains. These bacteriocins were compared with respect to their ability to produce spheroplasts in a sensitive indicator strain; their inducibility; sensitivity to pH, proteolytic enzymes, and boiling; and their effect on macromolecular synthesis. Two bacteriocins were stable over a wide range of pH values and resisted boiling, and three bacteriocins were resistant to trypsin. Five bacteriocins shut down DNA, RNA, and protein synthesis; three bacteriocins had varying effects on DNA and RNA synthesis; and two bacteriocins had little effect on macromolecular synthesis. Antiserum prepared against one bacteriocin highly neutralized three bacteriocins with partial neutralization of five others; two bacteriocins were unaffected. Mutant strains selected for resistance to bacteriocin 28 also demonstrated coresistance to two other closely related bacteriocins and partial resistance to five others.", "contents": "Comparative study of ten bacteriocins of Clostridium perfringens. Bacteriocins of Clostridium perfringens were prepared by ammonium sulfate precipitation of supernatant broth from 10 bacteriocinogenic strains. These bacteriocins were compared with respect to their ability to produce spheroplasts in a sensitive indicator strain; their inducibility; sensitivity to pH, proteolytic enzymes, and boiling; and their effect on macromolecular synthesis. Two bacteriocins were stable over a wide range of pH values and resisted boiling, and three bacteriocins were resistant to trypsin. Five bacteriocins shut down DNA, RNA, and protein synthesis; three bacteriocins had varying effects on DNA and RNA synthesis; and two bacteriocins had little effect on macromolecular synthesis. Antiserum prepared against one bacteriocin highly neutralized three bacteriocins with partial neutralization of five others; two bacteriocins were unaffected. Mutant strains selected for resistance to bacteriocin 28 also demonstrated coresistance to two other closely related bacteriocins and partial resistance to five others."}
{"id": "PMID:217303", "title": "Polymyxin B-penicillin antagonism in Proteus mirabilis.", "content": "Polymyxin B protects Proteus mirabilis from usually lethal penicillin concentrations.", "contents": "Polymyxin B-penicillin antagonism in Proteus mirabilis. Polymyxin B protects Proteus mirabilis from usually lethal penicillin concentrations."}
{"id": "PMID:217304", "title": "Cell killing by Simian virus 40: protective effect of chloroquine.", "content": "Treatment of CV-1 cells with chloroquine before infection by simian virus 40 resulted in the accumulation of fewer nonviable, trypan blue-stainable cells at 72 h. The drug did not affect the fraction of infected T-antigen-producing cells or the viral yields. It did diminish the apparent redistribution of lysosomal N-acetyl-beta-glucosaminidase from a particulate to a soluble cell fraction, and it caused an increase in the size and number of lysosomes.", "contents": "Cell killing by Simian virus 40: protective effect of chloroquine. Treatment of CV-1 cells with chloroquine before infection by simian virus 40 resulted in the accumulation of fewer nonviable, trypan blue-stainable cells at 72 h. The drug did not affect the fraction of infected T-antigen-producing cells or the viral yields. It did diminish the apparent redistribution of lysosomal N-acetyl-beta-glucosaminidase from a particulate to a soluble cell fraction, and it caused an increase in the size and number of lysosomes."}
{"id": "PMID:217315", "title": "On betaH-Leu5-endorphin and schizophrenia.", "content": "A previously unknown peptide, betaH-Leu5-endorphin, has been reported in the dialysates of schizophrenic patients. Accordingly, hemofiltrates from two schizophrenic and two control patients were examined for the presence of betaH-Leu5-endorphin. The opioid peptides were detected by a radioreceptor assay after separation and identification by gel filtration and high-performance liquid chromatography. With a detection limit of 30 pmole/L of hemofiltrate, no betaH-Leu5-endorphin or Met5-endorphin was found in controls or in patients. Whatever the possible involvement of endorphins in schizophrenic behavior, they are not present at detectable levels in the hemofiltrates of two well-characterized schizophrenic patients, thereby casting doubt on a general relationship of Leu-endorphin and schizophrenia.", "contents": "On betaH-Leu5-endorphin and schizophrenia. A previously unknown peptide, betaH-Leu5-endorphin, has been reported in the dialysates of schizophrenic patients. Accordingly, hemofiltrates from two schizophrenic and two control patients were examined for the presence of betaH-Leu5-endorphin. The opioid peptides were detected by a radioreceptor assay after separation and identification by gel filtration and high-performance liquid chromatography. With a detection limit of 30 pmole/L of hemofiltrate, no betaH-Leu5-endorphin or Met5-endorphin was found in controls or in patients. Whatever the possible involvement of endorphins in schizophrenic behavior, they are not present at detectable levels in the hemofiltrates of two well-characterized schizophrenic patients, thereby casting doubt on a general relationship of Leu-endorphin and schizophrenia."}
{"id": "PMID:217317", "title": "[Pancreatic lesion in newborn mice caused by Coxsackie B1 virus].", "content": "Changes in the pancreatic gland manifested by necrosis of excretory cells and marked atrophy of insulae with the loss of beta-cells producing insulin were observed experimentally in suckling mice infected with Coxsackie B1 virus. It is suggested that the above changes of the pancreas may be a model of human diseases caused by Coxsackie viruses, including a model of development of some cases of diabetes.", "contents": "[Pancreatic lesion in newborn mice caused by Coxsackie B1 virus]. Changes in the pancreatic gland manifested by necrosis of excretory cells and marked atrophy of insulae with the loss of beta-cells producing insulin were observed experimentally in suckling mice infected with Coxsackie B1 virus. It is suggested that the above changes of the pancreas may be a model of human diseases caused by Coxsackie viruses, including a model of development of some cases of diabetes."}
{"id": "PMID:217318", "title": "'Locked-in coma' in postinfective polyneuropathy.", "content": "A patient with postinfective cranial and peripheral polyneuropathy exhibited the electroencephalographic and behavioral features of \"alpha coma\". The relation of this form of extensive peripheral disconnection to those cases with central disconnection due to pontomesencephalic lesions is discussed. We conclude that in both situations further evaluation of brain stem and cortical function is necessary to determine whether or not consciousness is preserved, rather than relying solely on the presence of ocular movements and reactivity of the electroencephalogram.", "contents": "'Locked-in coma' in postinfective polyneuropathy. A patient with postinfective cranial and peripheral polyneuropathy exhibited the electroencephalographic and behavioral features of \"alpha coma\". The relation of this form of extensive peripheral disconnection to those cases with central disconnection due to pontomesencephalic lesions is discussed. We conclude that in both situations further evaluation of brain stem and cortical function is necessary to determine whether or not consciousness is preserved, rather than relying solely on the presence of ocular movements and reactivity of the electroencephalogram."}
{"id": "PMID:217320", "title": "Russell bodies in contact-lens-associated giant papillary conjunctivitis.", "content": "Biopsy specimens of the upper tarsal conjunctiva in soft contact lens-associated giant papillary conjunctivitis were taken during (1) chronic exacerbation, (2) brief remission, and (3) intentional exacerbation. Inflammatory cells were quantitated and compared with inflammatory cells in normal upper tarsal conjunctivae. Specimens were evaluated by light and electron microscopy. The most remarkable feature was the presence of diamond-shaped Russell bodies in 20% of the plasma cells of the second biopsy specimen. A few round Russell bodies were seen in the first biopsy specimen and none in the third. We concluded that the brief quiescent phase (second biopsy specimen) was characterized by retention of immunoglobulin to produce Russell bodies, and that the active phases of the disease were marked by migration of mast cells into the epithelium and by the presence of eosinophils and basophils in the substantia propria.", "contents": "Russell bodies in contact-lens-associated giant papillary conjunctivitis. Biopsy specimens of the upper tarsal conjunctiva in soft contact lens-associated giant papillary conjunctivitis were taken during (1) chronic exacerbation, (2) brief remission, and (3) intentional exacerbation. Inflammatory cells were quantitated and compared with inflammatory cells in normal upper tarsal conjunctivae. Specimens were evaluated by light and electron microscopy. The most remarkable feature was the presence of diamond-shaped Russell bodies in 20% of the plasma cells of the second biopsy specimen. A few round Russell bodies were seen in the first biopsy specimen and none in the third. We concluded that the brief quiescent phase (second biopsy specimen) was characterized by retention of immunoglobulin to produce Russell bodies, and that the active phases of the disease were marked by migration of mast cells into the epithelium and by the presence of eosinophils and basophils in the substantia propria."}
{"id": "PMID:217324", "title": "Psoriasis: a medical mystery?", "content": "Psoriasis remains a disease of unknown aetiology. It is common, has a chronic course with exacerbations and remissions, and may present at any age. There are a number of clinical types recognized and an association with arthritis has been noted. Treatment is directed at control of the disease to enable the person to live and cope with his disease state. This can often be achieved with topical therapy, but it may at times require hospitalization. More severe forms of psoriasis may require potentially dangerous medication.", "contents": "Psoriasis: a medical mystery? Psoriasis remains a disease of unknown aetiology. It is common, has a chronic course with exacerbations and remissions, and may present at any age. There are a number of clinical types recognized and an association with arthritis has been noted. Treatment is directed at control of the disease to enable the person to live and cope with his disease state. This can often be achieved with topical therapy, but it may at times require hospitalization. More severe forms of psoriasis may require potentially dangerous medication."}
{"id": "PMID:217327", "title": "Primary, severe, combined immunodeficiency disease of Arabian foals.", "content": "Set in a context of immunodeficiency diseases in general this paper provides a brief, illustrated review of a primary, severe, combined immunodeficiency (PSCID) disease of Arabian foals. Affected foals are clinically normal at birth but beginning at about 10 days of age they develop a range of clinical signs particularly bronchopneumonia and diarrhoea with which adenoviruses are peculiarly associated. Despite intensive therapy foals invariably die by about 3 months of age. Affected foals are profoundly lymphopagenic (greater than 1000 lymphcoytes per mm3). There is thymic and lymph node hypoplasia and all lymphoid tissues are profoundly depleted of both T and B lymphocytes. The depletion of both T and B lymphocytes suggests that the primary defect is at the level of bone marrow stem cells which are the precursor cells for both lymphocyte populations. PSCID of Arabian foals is inherited as a simple, autosomal, recessive gene. Some 2 to 3% of all such foals may be born with PSCID, this frequency corresponds to a gene frequency of about 30% in parents. The syndrome is, therefore, an important cause of economic wastage. It also represents the only occurrence of the syndrome in an animal species other than man and as such has considerable comparative interest.", "contents": "Primary, severe, combined immunodeficiency disease of Arabian foals. Set in a context of immunodeficiency diseases in general this paper provides a brief, illustrated review of a primary, severe, combined immunodeficiency (PSCID) disease of Arabian foals. Affected foals are clinically normal at birth but beginning at about 10 days of age they develop a range of clinical signs particularly bronchopneumonia and diarrhoea with which adenoviruses are peculiarly associated. Despite intensive therapy foals invariably die by about 3 months of age. Affected foals are profoundly lymphopagenic (greater than 1000 lymphcoytes per mm3). There is thymic and lymph node hypoplasia and all lymphoid tissues are profoundly depleted of both T and B lymphocytes. The depletion of both T and B lymphocytes suggests that the primary defect is at the level of bone marrow stem cells which are the precursor cells for both lymphocyte populations. PSCID of Arabian foals is inherited as a simple, autosomal, recessive gene. Some 2 to 3% of all such foals may be born with PSCID, this frequency corresponds to a gene frequency of about 30% in parents. The syndrome is, therefore, an important cause of economic wastage. It also represents the only occurrence of the syndrome in an animal species other than man and as such has considerable comparative interest."}
{"id": "PMID:217329", "title": "The hypercoagulable state and pulmonary embolism in patients with ovarian carcinoma.", "content": "Fifty-nine patients with ovarian carcinoma were studied with particular reference to abnormalities of the coagulation mechanism. The notable findings were the high incidence of episodic thrombocytosis (73%) and the relation of these peaks of thrombocytosis to periods of expected maximum tumour break-down. The incidence of pulmonary embolism for the series was 44%, with the majority occurring in the group demonstrating significant thrombocytosis; in this latter group, pulmonary embolism constituted the major cause of death. The abnormalities in coagulation are discussed, together with pragmatic significance and methods of control.", "contents": "The hypercoagulable state and pulmonary embolism in patients with ovarian carcinoma. Fifty-nine patients with ovarian carcinoma were studied with particular reference to abnormalities of the coagulation mechanism. The notable findings were the high incidence of episodic thrombocytosis (73%) and the relation of these peaks of thrombocytosis to periods of expected maximum tumour break-down. The incidence of pulmonary embolism for the series was 44%, with the majority occurring in the group demonstrating significant thrombocytosis; in this latter group, pulmonary embolism constituted the major cause of death. The abnormalities in coagulation are discussed, together with pragmatic significance and methods of control."}
{"id": "PMID:217330", "title": "Application of a bubble formation model to decompression sickness in rats and humans.", "content": "Although decompression sickness results from bubble formation in blood or tissue, pressure schedules currently in use are essentially empirical and contain little input from cavitation theory. The recent convergence of three lines of investigation suggests that a synthesis of practice and theory may now be possible. The data consist of pressure reduction limits for gelatin, rats, and humans following steady-state exposures. From the gelatin studies, a model has been developed in which bubble formation is initiated by spherical gas nuclei stabilized by surface-active skins of varying gas permeability. We demonstrate that the model is also in good agreement with data on rats and humans over a wide range of pressures and that the model parameters assume sensible values in each case. This suggests that cavitation theory can provide a rationale for current diving practice and can serve to secure, consolidate, and extend this practice.", "contents": "Application of a bubble formation model to decompression sickness in rats and humans. Although decompression sickness results from bubble formation in blood or tissue, pressure schedules currently in use are essentially empirical and contain little input from cavitation theory. The recent convergence of three lines of investigation suggests that a synthesis of practice and theory may now be possible. The data consist of pressure reduction limits for gelatin, rats, and humans following steady-state exposures. From the gelatin studies, a model has been developed in which bubble formation is initiated by spherical gas nuclei stabilized by surface-active skins of varying gas permeability. We demonstrate that the model is also in good agreement with data on rats and humans over a wide range of pressures and that the model parameters assume sensible values in each case. This suggests that cavitation theory can provide a rationale for current diving practice and can serve to secure, consolidate, and extend this practice."}
{"id": "PMID:217337", "title": "Electrophoretic heterogeneity of 5-phosphoribosyl-1-pyrophosphate synthetase within and among humans.", "content": "The product of the enzyme 5-phosphoribosyl-1-pyrophosphate (PPriboseP) synthetase is a substrate for purine, pyrimidine, and pyridine biosynthesis and may be rate limiting for purine biosynthesis. A system developed to electrophoretically separate and histochemically detect PPriboseP synthetase in crude cell extracts has facilitated the identification of electrophoretically variant enzyme forms in the erythrocytes of five patients from a patient population of 200. Additional studies of human organs obtained at autopsy revealed a unique electrophoretic mobility for nearly each organ within the same individual.", "contents": "Electrophoretic heterogeneity of 5-phosphoribosyl-1-pyrophosphate synthetase within and among humans. The product of the enzyme 5-phosphoribosyl-1-pyrophosphate (PPriboseP) synthetase is a substrate for purine, pyrimidine, and pyridine biosynthesis and may be rate limiting for purine biosynthesis. A system developed to electrophoretically separate and histochemically detect PPriboseP synthetase in crude cell extracts has facilitated the identification of electrophoretically variant enzyme forms in the erythrocytes of five patients from a patient population of 200. Additional studies of human organs obtained at autopsy revealed a unique electrophoretic mobility for nearly each organ within the same individual."}
{"id": "PMID:217338", "title": "Microheterogeneity of adenosine cyclic monophosphate-dependent protein kinases from mouse brain and heart.", "content": "1. DEAE-cellulose chromatography of mouse brain cytosol indicated the presence of only the type II isoenzyme of cyclic AMP-dependent protein kinase. Mouse heart cytosol contained approximately equal amounts of the type I and type II isoenzymes. 2. Both brain and heart type II isoenzymes reassociated after a transient exposure to cyclic AMP, but the heart type I isoenzyme remained dissociated. 3. Elution of brain cytosol continuously exposed to cyclic AMP resolved multiple peaks of protein kinase and cyclic AMP-binding activities. A single peak of kinase and multiple peaks of cyclic AMP-binding activities were found under the same conditions with heart cytosol. Various control experiments suggested that the heterogeneity within the brain type II isoenzymic class had not been caused by proteolysis. 4. Kinetic experiments with unfractionated brain cytosol showed that the binding of cyclic AMP, the dissociation of cyclic AMP from protein and the rate of heat denaturation of the cyclic AMP-binding activity gave results consistent with the presence of multiple binding species. 5. It concluded that the type II isoenzymic peak obtained by DEAE-cellulose chromatography of mouse brain cytosol represents a class of enzymes containing multiple regulatory and catalytic subunits. The two heart cytosol isoenzymes contain a common catalytic subunit. The degree of protein kinase 'microheterogeneity\", defined as the presence of multiple regulatory and/or catalytic subunits within a single isoenzymic class, appears to be tissue-specific.", "contents": "Microheterogeneity of adenosine cyclic monophosphate-dependent protein kinases from mouse brain and heart. 1. DEAE-cellulose chromatography of mouse brain cytosol indicated the presence of only the type II isoenzyme of cyclic AMP-dependent protein kinase. Mouse heart cytosol contained approximately equal amounts of the type I and type II isoenzymes. 2. Both brain and heart type II isoenzymes reassociated after a transient exposure to cyclic AMP, but the heart type I isoenzyme remained dissociated. 3. Elution of brain cytosol continuously exposed to cyclic AMP resolved multiple peaks of protein kinase and cyclic AMP-binding activities. A single peak of kinase and multiple peaks of cyclic AMP-binding activities were found under the same conditions with heart cytosol. Various control experiments suggested that the heterogeneity within the brain type II isoenzymic class had not been caused by proteolysis. 4. Kinetic experiments with unfractionated brain cytosol showed that the binding of cyclic AMP, the dissociation of cyclic AMP from protein and the rate of heat denaturation of the cyclic AMP-binding activity gave results consistent with the presence of multiple binding species. 5. It concluded that the type II isoenzymic peak obtained by DEAE-cellulose chromatography of mouse brain cytosol represents a class of enzymes containing multiple regulatory and catalytic subunits. The two heart cytosol isoenzymes contain a common catalytic subunit. The degree of protein kinase 'microheterogeneity\", defined as the presence of multiple regulatory and/or catalytic subunits within a single isoenzymic class, appears to be tissue-specific."}
{"id": "PMID:217339", "title": "The metabolic modification of low-density lipoproteins in normal and hypercholesterolaemic guinea pigs.", "content": "1. Low-density lipoproteins were isolated by ultracentrifugation from the serum of guinea pigs that were fed either on a normal diet, or on a diet supplemented with corn oil and cholesterol. 2. After labelling with tracer amounts of radioactive iodine, these lipoproteins were injected into the bloodstream of guinea pigs that were fed either on the normal or on the supplemented diet. 3. In all cases, the density of the labelled lipoproteins was increased by exposure for 24-48 h to the metabolic processes of the guinea pig. 4. The final density reached by lipoproteins isolated from fat-fed guinea pigs was less than that reached by lipoproteins from normal animals. 5. Fat-fed guinea pigs were unable to increase the density of either normal lipoproteins, or those from fat-fed guinea pits, to the same extent as animals fed on the normal diet. 6. It is concluded that the lipid-rich diet brings about a modification of lipoprotein metabolism in the guinea, pig, which plays an important part in determining the nature of the nature of the low-density lipoprotein that is present in the plasma.", "contents": "The metabolic modification of low-density lipoproteins in normal and hypercholesterolaemic guinea pigs. 1. Low-density lipoproteins were isolated by ultracentrifugation from the serum of guinea pigs that were fed either on a normal diet, or on a diet supplemented with corn oil and cholesterol. 2. After labelling with tracer amounts of radioactive iodine, these lipoproteins were injected into the bloodstream of guinea pigs that were fed either on the normal or on the supplemented diet. 3. In all cases, the density of the labelled lipoproteins was increased by exposure for 24-48 h to the metabolic processes of the guinea pig. 4. The final density reached by lipoproteins isolated from fat-fed guinea pigs was less than that reached by lipoproteins from normal animals. 5. Fat-fed guinea pigs were unable to increase the density of either normal lipoproteins, or those from fat-fed guinea pits, to the same extent as animals fed on the normal diet. 6. It is concluded that the lipid-rich diet brings about a modification of lipoprotein metabolism in the guinea, pig, which plays an important part in determining the nature of the nature of the low-density lipoprotein that is present in the plasma."}
{"id": "PMID:217340", "title": "Effect of beta-lapachone on superoxide anion and hydrogen peroxide production in Trypanosoma cruzi.", "content": "Addition of beta-lapachone, an o-naphthoquinone endowed with trypanocidal properties to respiring Trypanosoma cruzi epimastigotes induced the release of O2- and H2O2 from the whole cells to the suspending medium. The same beta-lapachone concentration (4 micron) that released H2O2 at maximal rate completely inhibited T. cruzi growth in a liquid medium. The position  isomer, alpha-lapachone, did not stimulate O2- and H2O2 release, and did not inhibit epimastigote growth. beta-Lapachone was able to stimulate H2O2 production by the epimastigote homogenate in the presence of NADH as reductant. The same effect was observed with the mitochondrial fraction supplemented with NADH, where beta-lapachone enhanced the generation of O2- and H2O2 4.5- and 2.5-fold  respectively. beta-Lapachone also increased O2- and H2O2 production (2.5 and 2-fold respectively) by the microsomal fraction with NADPH as reductant. Cyanide-insensitive NADH and NADPH oxidation by the mitochondrial and microsomal fractions (quinone reductase activity) was stimulated to about the same extent by beta-lapachone. alpha-Lapachone was unable to increase O2- and H2O2 production and quinone reductase activity of the mitochondrial and microsomal fractions.", "contents": "Effect of beta-lapachone on superoxide anion and hydrogen peroxide production in Trypanosoma cruzi. Addition of beta-lapachone, an o-naphthoquinone endowed with trypanocidal properties to respiring Trypanosoma cruzi epimastigotes induced the release of O2- and H2O2 from the whole cells to the suspending medium. The same beta-lapachone concentration (4 micron) that released H2O2 at maximal rate completely inhibited T. cruzi growth in a liquid medium. The position  isomer, alpha-lapachone, did not stimulate O2- and H2O2 release, and did not inhibit epimastigote growth. beta-Lapachone was able to stimulate H2O2 production by the epimastigote homogenate in the presence of NADH as reductant. The same effect was observed with the mitochondrial fraction supplemented with NADH, where beta-lapachone enhanced the generation of O2- and H2O2 4.5- and 2.5-fold  respectively. beta-Lapachone also increased O2- and H2O2 production (2.5 and 2-fold respectively) by the microsomal fraction with NADPH as reductant. Cyanide-insensitive NADH and NADPH oxidation by the mitochondrial and microsomal fractions (quinone reductase activity) was stimulated to about the same extent by beta-lapachone. alpha-Lapachone was unable to increase O2- and H2O2 production and quinone reductase activity of the mitochondrial and microsomal fractions."}
{"id": "PMID:217341", "title": "Incorportion of oxygen-18 into the 25-position of cholecalciferol by hepatic cholecalciferol 25-hydroxylase.", "content": "The oxygen enzymically inserted as a hydroxy function by rat liver post-mitochondrial fraction into the 25-position of cholecalciferol to giver 25-hydroxycholecaliferol is derived exclusively from molecular O2. Therefore like the other two cholecalciferol hydroxylases, i.e. 25-hydroxycholecalciferol 1alpha-hydroxylase and 25-hydroxycholecalciferol 24-hydroxylase, the cholecalciferol 25-hydroxylase is also a mono-oxygenase ('mixed-function oxidase').", "contents": "Incorportion of oxygen-18 into the 25-position of cholecalciferol by hepatic cholecalciferol 25-hydroxylase. The oxygen enzymically inserted as a hydroxy function by rat liver post-mitochondrial fraction into the 25-position of cholecalciferol to giver 25-hydroxycholecaliferol is derived exclusively from molecular O2. Therefore like the other two cholecalciferol hydroxylases, i.e. 25-hydroxycholecalciferol 1alpha-hydroxylase and 25-hydroxycholecalciferol 24-hydroxylase, the cholecalciferol 25-hydroxylase is also a mono-oxygenase ('mixed-function oxidase')."}
{"id": "PMID:217342", "title": "Purification and properties of nitrite reductase from Escherichia coli K12.", "content": "NADH-nitrite oxidoreductase (EC 1.6.4) was purified to better than 95% homogeneity from batch cultures of Escherichia coli strain OR75Ch15, which is partially constitutive for nitrite reductase synthesis. Yields of purified enzyme were low, mainly because of a large loss of activity during chromatography on DEAE-cellulose. The quantitative separation of cytochrome c-552 from nitrite reductase activity resulted in an increase in the specific activity of the enzyme: this cytochrome is not therefore an integral part of nitrite reductase. The subunit molecular weights of nitrite reductase and of a haemoprotein contaminant, as determined by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, were 88000 and 80000 respectively. The sedimentation coefficient was calculated to be in the range 8.5-9.5S, consistent with a mol.wt. of 190000. It is suggested therefore that the native enzyme is a dimer with two identical or similar-sized subunits. Purest samples contained 0.4 mol of flavin/mol of enzyme, but no detectable haem. Catalytic activity was totally inhibited by 20 micron-p-chloromercuribenzoate and 1 mM-cyanide, slightly inhibited by 1 micron-sulphite and 10mM-arsenite, but insensitive to 1 mM-2,2'-bipyridine, 4mM-1,10-phenanthroline and 10mM-NaN3. Three molecules of NADH were oxidized for each NO2-ion reduced: the product of the reaction is therefore assumed to be NH4+. The specific activity of hydroxylamine reductase increased at each step in the purification of nitrite reductase, and the elution profiles for these two activities during chromatography on DEAE-Sephadex were coincident. It is likely that a single enzyme is responsible for both activities.", "contents": "Purification and properties of nitrite reductase from Escherichia coli K12. NADH-nitrite oxidoreductase (EC 1.6.4) was purified to better than 95% homogeneity from batch cultures of Escherichia coli strain OR75Ch15, which is partially constitutive for nitrite reductase synthesis. Yields of purified enzyme were low, mainly because of a large loss of activity during chromatography on DEAE-cellulose. The quantitative separation of cytochrome c-552 from nitrite reductase activity resulted in an increase in the specific activity of the enzyme: this cytochrome is not therefore an integral part of nitrite reductase. The subunit molecular weights of nitrite reductase and of a haemoprotein contaminant, as determined by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, were 88000 and 80000 respectively. The sedimentation coefficient was calculated to be in the range 8.5-9.5S, consistent with a mol.wt. of 190000. It is suggested therefore that the native enzyme is a dimer with two identical or similar-sized subunits. Purest samples contained 0.4 mol of flavin/mol of enzyme, but no detectable haem. Catalytic activity was totally inhibited by 20 micron-p-chloromercuribenzoate and 1 mM-cyanide, slightly inhibited by 1 micron-sulphite and 10mM-arsenite, but insensitive to 1 mM-2,2'-bipyridine, 4mM-1,10-phenanthroline and 10mM-NaN3. Three molecules of NADH were oxidized for each NO2-ion reduced: the product of the reaction is therefore assumed to be NH4+. The specific activity of hydroxylamine reductase increased at each step in the purification of nitrite reductase, and the elution profiles for these two activities during chromatography on DEAE-Sephadex were coincident. It is likely that a single enzyme is responsible for both activities."}
{"id": "PMID:217343", "title": "Activation of nitrite reductase from Escherichia coli K12 by oxidized nicotinamide-adenine dinucleotide.", "content": "Nitrite reductase from Escherichia coli K12 requires the presence of NAD+, one of the products of the reduction of NO2-by NADH, for full activity. The effect is observed with both crude extracts and purified enzyme. NAD+ also acts as a product inhibitor at high concentrations, and plots of initial rate against NAD+ concentration are bell-shaped. The maximum occurs at about 1 mM-NAD+, but increases with increasing NADH concentration. In the presence of 1 mM-NAD+ and saturating NO2-(2mM) the Michaelis constant for NADH is about 16 micron. The Michaelis constant for NO2-is about 5 micron and is largely independent of the NAD+ concentration. Similar but more pronounced effects of NAD+ are observed with hydroxylamine as electron acceptor instead of NO2-. The maximum rate of NADH oxidation by hydroxylamine is about 5.4 times greater than the maximum rate of NADH oxidation by NO2- when assayed with the same volume of the same preparation of purified enzyme. The Michaelis constant for hydroxylamine is 5.3 mM, however, about 1000 times higher than for NO2-. These results are consistent with a mechanism in which the same enzyme-hydroxylamine complex occurs as an intermediate in both reactions.", "contents": "Activation of nitrite reductase from Escherichia coli K12 by oxidized nicotinamide-adenine dinucleotide. Nitrite reductase from Escherichia coli K12 requires the presence of NAD+, one of the products of the reduction of NO2-by NADH, for full activity. The effect is observed with both crude extracts and purified enzyme. NAD+ also acts as a product inhibitor at high concentrations, and plots of initial rate against NAD+ concentration are bell-shaped. The maximum occurs at about 1 mM-NAD+, but increases with increasing NADH concentration. In the presence of 1 mM-NAD+ and saturating NO2-(2mM) the Michaelis constant for NADH is about 16 micron. The Michaelis constant for NO2-is about 5 micron and is largely independent of the NAD+ concentration. Similar but more pronounced effects of NAD+ are observed with hydroxylamine as electron acceptor instead of NO2-. The maximum rate of NADH oxidation by hydroxylamine is about 5.4 times greater than the maximum rate of NADH oxidation by NO2- when assayed with the same volume of the same preparation of purified enzyme. The Michaelis constant for hydroxylamine is 5.3 mM, however, about 1000 times higher than for NO2-. These results are consistent with a mechanism in which the same enzyme-hydroxylamine complex occurs as an intermediate in both reactions."}
{"id": "PMID:217344", "title": "The specific interaction of cibacron and related dyes with cyclic nucleotide phosphodiesterase and lactate dehydrogenase.", "content": "1. Reactive Blue 2 (Cibacron Blue 3G-A) is a competitive inhibitor of bovine heart cyclic nucleotide phosphodiesterase (K(i) 0.3mum). The K(i) increases with increasing temperature, suggesting that hydrophobic interactions are not largely responsible for the binding of the dye. Another 25 sulphonated aromatic dyes are also competitive inhibitors of the cyclic nucleotide phosphodiesterase (K(i) values in the range of 0.06-13.6mum). 2. These dyes (covalently linked to Dextran 40) inhibit bovine heart cyclic nucleotide phosphodiesterase. Reactive Blue 2 (covalently linked to Dextran 40) is a competitive inhibitor of the phosphodiesterase (K(i) 0.4mum). 3. Bovine heart cyclic nucleotide phosphodiesterase is retained on a column of Reactive Blue 2-Sephacryl S-200 and can be eluted from the column by 3':5'-cyclic AMP. 4. A variety of the dyes (either free or covalently linked to Dextran 40) are competitive inhibitors of rabbit muscle lactate dehydrogenase. 5. The effectiveness of a wide range of structurally dissimilar dyes as competitive inhibitors of lactate dehydrogenase and cyclic nucleotide phosphodiesterase compromises proposals for the use of Reactive Blue 2 as a specific probe for the dinucleotide-binding structural domain present in many dehydrogenases and kinases. Detailed information of the various dyes used has been deposited as Supplementary Publication SUP 50089 (7 pages) at the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1978) 169, 5.", "contents": "The specific interaction of cibacron and related dyes with cyclic nucleotide phosphodiesterase and lactate dehydrogenase. 1. Reactive Blue 2 (Cibacron Blue 3G-A) is a competitive inhibitor of bovine heart cyclic nucleotide phosphodiesterase (K(i) 0.3mum). The K(i) increases with increasing temperature, suggesting that hydrophobic interactions are not largely responsible for the binding of the dye. Another 25 sulphonated aromatic dyes are also competitive inhibitors of the cyclic nucleotide phosphodiesterase (K(i) values in the range of 0.06-13.6mum). 2. These dyes (covalently linked to Dextran 40) inhibit bovine heart cyclic nucleotide phosphodiesterase. Reactive Blue 2 (covalently linked to Dextran 40) is a competitive inhibitor of the phosphodiesterase (K(i) 0.4mum). 3. Bovine heart cyclic nucleotide phosphodiesterase is retained on a column of Reactive Blue 2-Sephacryl S-200 and can be eluted from the column by 3':5'-cyclic AMP. 4. A variety of the dyes (either free or covalently linked to Dextran 40) are competitive inhibitors of rabbit muscle lactate dehydrogenase. 5. The effectiveness of a wide range of structurally dissimilar dyes as competitive inhibitors of lactate dehydrogenase and cyclic nucleotide phosphodiesterase compromises proposals for the use of Reactive Blue 2 as a specific probe for the dinucleotide-binding structural domain present in many dehydrogenases and kinases. Detailed information of the various dyes used has been deposited as Supplementary Publication SUP 50089 (7 pages) at the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1978) 169, 5."}
{"id": "PMID:217345", "title": "Inhibition of deoxyribonucleic acid polymerases from human cells and from simian sarcoma virus by pyran.", "content": "Pyrans are co-polymers of divinyl ether and maleic anhydride. Four pyrans of various molecular weights more potently inhibited terminal deoxyribonucleotidyltransferase (EC 2.7.7.31) from a human cell line of acute lymphoblastic leukemia origin (Molt-4) than they did DNA polymerases alpha, beta and gamma from these cells and DNA polymerase from simian sarcoma virus. For example, the concentrations of one pyran required for 50% inhibition of terminal deoxynucleotidyltransferase, DNA polymerases alpha, beta and gamma and viral DNA polymerase were 0.9, 110, 125, 35 and 47 microgram/ml respectively. Quantitatively similar results were obtained with the other pyrans. Inhibition of these enzymes by pyran was dependent on the concentrations of both the bivalent cation and template/primer or initiator in assay mixtures, but not on the concentrations of the substrate (deoxyribonucleoside 5'-triphosphate), enzyme, or bovine serum albumin. These results suggested that pyran inhibited these enzymes by complexing bivalent cations, which caused a decreased affinity of template/primer or initiator for each enzyme and a decrease in enzyme activity.", "contents": "Inhibition of deoxyribonucleic acid polymerases from human cells and from simian sarcoma virus by pyran. Pyrans are co-polymers of divinyl ether and maleic anhydride. Four pyrans of various molecular weights more potently inhibited terminal deoxyribonucleotidyltransferase (EC 2.7.7.31) from a human cell line of acute lymphoblastic leukemia origin (Molt-4) than they did DNA polymerases alpha, beta and gamma from these cells and DNA polymerase from simian sarcoma virus. For example, the concentrations of one pyran required for 50% inhibition of terminal deoxynucleotidyltransferase, DNA polymerases alpha, beta and gamma and viral DNA polymerase were 0.9, 110, 125, 35 and 47 microgram/ml respectively. Quantitatively similar results were obtained with the other pyrans. Inhibition of these enzymes by pyran was dependent on the concentrations of both the bivalent cation and template/primer or initiator in assay mixtures, but not on the concentrations of the substrate (deoxyribonucleoside 5'-triphosphate), enzyme, or bovine serum albumin. These results suggested that pyran inhibited these enzymes by complexing bivalent cations, which caused a decreased affinity of template/primer or initiator for each enzyme and a decrease in enzyme activity."}
{"id": "PMID:217346", "title": "Oxidation of 2-nitropropane by horseradish peroxidase. Involvement of hydrogen peroxide and of superoxide in the reaction mechanism.", "content": "Incubation of aqueous solutions of 2-nitropropane in air causes a slow oxidation reaction that generates H(2)O(2). Purified horseradish peroxidase catalyses the oxidation of such preincubated 2-nitropropane solutions according to the equation: [Formula: see text] The pH optimum is 4.5 and K(m) for 2-nitropropane is 16mm. Other nitroalkanes or nitro-aromatics tested are not oxidized at significant rates by peroxidase. H(2)O(2) or 2,4-dichlorophenol increases the rate of 2-nitropropane oxidation by peroxidase. Catalase inhibits the reaction completely. Superoxide dismutase or mannitol, a scavenger of the hydroxyl radical, OH(.), each inhibits partially. Aniline and guaiacol are also powerful inhibitors of 2-nitropropane oxidation. It is suggested that peroxidase uses the traces of H(2)O(2) generated during preincubation of 2-nitropropane to catalyse oxidation of this substrate into a radical species that can reduce O(2) to the superoxide ion, O(2) (-.).O(2) (-.), or OH(.) derived from it, then appears to react with more nitropropane, generating further radicals and H(2)O(2) to continue the oxidation. Inhibition by aniline and guaiacol seems to be due to a competition for H(2)O(2).", "contents": "Oxidation of 2-nitropropane by horseradish peroxidase. Involvement of hydrogen peroxide and of superoxide in the reaction mechanism. Incubation of aqueous solutions of 2-nitropropane in air causes a slow oxidation reaction that generates H(2)O(2). Purified horseradish peroxidase catalyses the oxidation of such preincubated 2-nitropropane solutions according to the equation: [Formula: see text] The pH optimum is 4.5 and K(m) for 2-nitropropane is 16mm. Other nitroalkanes or nitro-aromatics tested are not oxidized at significant rates by peroxidase. H(2)O(2) or 2,4-dichlorophenol increases the rate of 2-nitropropane oxidation by peroxidase. Catalase inhibits the reaction completely. Superoxide dismutase or mannitol, a scavenger of the hydroxyl radical, OH(.), each inhibits partially. Aniline and guaiacol are also powerful inhibitors of 2-nitropropane oxidation. It is suggested that peroxidase uses the traces of H(2)O(2) generated during preincubation of 2-nitropropane to catalyse oxidation of this substrate into a radical species that can reduce O(2) to the superoxide ion, O(2) (-.).O(2) (-.), or OH(.) derived from it, then appears to react with more nitropropane, generating further radicals and H(2)O(2) to continue the oxidation. Inhibition by aniline and guaiacol seems to be due to a competition for H(2)O(2)."}
{"id": "PMID:217347", "title": "An enzyme degrading reduced nicotinamide-adenine dinucleotide in Proteus vulgaris.", "content": "Cell-free extracts of a strain of Proteus vulgaris degrade NADH to reduced nicotinamide riboside, adenosine and two molecules of phosphate. The system is weakly active in fresh cell extracts, but activity is increased about 10-fold on rapid heating to 70-100 degrees C. On returning to room temperature, the activity returns rapidly to its initial low value but can be re-activated by again heating to 70-100 degrees C. Reversible activation can also be effected by extremes of pH or by teatment with 8M-urea. Activation appears to be due to reversible changes in conformation of the protein of the enzyme rather than to combination of the enzyme with a heat-labile inhibitor. The active form can be stabilized by addition of PPi. The system, which also possesses 5'-nucleotidase activity not separable from the NADH pyrophosphatase, requires Co2+ (0.4mM) for maximum activity. Although activated at relatively high temperatures, it is not enzymically active until cooled to 50-60 degrees C. It may be purified by affinity chromatography (with NAD+ as ligand) to an activity over 400 times that of the crude cell extract, and yields only one major band on polyacrylamide-gel electrophoresis.", "contents": "An enzyme degrading reduced nicotinamide-adenine dinucleotide in Proteus vulgaris. Cell-free extracts of a strain of Proteus vulgaris degrade NADH to reduced nicotinamide riboside, adenosine and two molecules of phosphate. The system is weakly active in fresh cell extracts, but activity is increased about 10-fold on rapid heating to 70-100 degrees C. On returning to room temperature, the activity returns rapidly to its initial low value but can be re-activated by again heating to 70-100 degrees C. Reversible activation can also be effected by extremes of pH or by teatment with 8M-urea. Activation appears to be due to reversible changes in conformation of the protein of the enzyme rather than to combination of the enzyme with a heat-labile inhibitor. The active form can be stabilized by addition of PPi. The system, which also possesses 5'-nucleotidase activity not separable from the NADH pyrophosphatase, requires Co2+ (0.4mM) for maximum activity. Although activated at relatively high temperatures, it is not enzymically active until cooled to 50-60 degrees C. It may be purified by affinity chromatography (with NAD+ as ligand) to an activity over 400 times that of the crude cell extract, and yields only one major band on polyacrylamide-gel electrophoresis."}
{"id": "PMID:217348", "title": "The kinetics and thermodynamics of the reaction of solid-state fully reduced membrane-bound cytochrome oxidase with carbon monoxide as studied by dual-wavelength multichannel spectroscopy and flash photolysis.", "content": "1. The results of non-linear optimization studies on the mechanism of reaction of solid-state fully reduced membrane-bound cytochrome oxidase with CO over the 178--203 K range are presented. The analysis is carried out on data obtained by dual-wavelength multichannel spectroscopy at three wavelength pairs (444--463 nm, 590--630 nm and 608--630 nm), which yield three distinct progress curves. The only model that satisfies the triple requirement of a standard deviation within the standard error of the data, a random distribution of residuals and good determination of the optimized parameters is a two-species sequential mechanism: flash photolysis yields unliganded cytochrome oxidase and free CO, which then recombine to form species Ic; Ic is then converted into species IIc, which is identical with the cytochrome oxidase-CO complex existing before flash photolysis. All the thermodynamic parameters describing this model are calculated. 2. On the basis of the data obtained from this paper, together with data from potentiometric studies, magnetic susceptibility measurements and i.r. spectroscopy, the chemical identity of the species is suggested.", "contents": "The kinetics and thermodynamics of the reaction of solid-state fully reduced membrane-bound cytochrome oxidase with carbon monoxide as studied by dual-wavelength multichannel spectroscopy and flash photolysis. 1. The results of non-linear optimization studies on the mechanism of reaction of solid-state fully reduced membrane-bound cytochrome oxidase with CO over the 178--203 K range are presented. The analysis is carried out on data obtained by dual-wavelength multichannel spectroscopy at three wavelength pairs (444--463 nm, 590--630 nm and 608--630 nm), which yield three distinct progress curves. The only model that satisfies the triple requirement of a standard deviation within the standard error of the data, a random distribution of residuals and good determination of the optimized parameters is a two-species sequential mechanism: flash photolysis yields unliganded cytochrome oxidase and free CO, which then recombine to form species Ic; Ic is then converted into species IIc, which is identical with the cytochrome oxidase-CO complex existing before flash photolysis. All the thermodynamic parameters describing this model are calculated. 2. On the basis of the data obtained from this paper, together with data from potentiometric studies, magnetic susceptibility measurements and i.r. spectroscopy, the chemical identity of the species is suggested."}
{"id": "PMID:217349", "title": "Partial reversal of the acetaldehyde and butyraldehyde oxidation reactions catalysed by aldehyde dehydrogenases from sheep liver.", "content": "In the presence of acetic anhydride or butyric anhydride, liver aldehyde dehydrogenases catalyse the oxidation of NADH at pH 7.0 and 25 degrees C. The maximum velocities and Michaelis constants for NADH at saturating anhydride concentrations are independent of which anhydride is used, the values being V'max. = 12 min-1 and Km for NADH = 9 micrometer for the mitochondrial enzyme and V'max = 25 min-1 and Km for NADH = 20 micrometer for the cytoplasmic enzyme. Substitution of [4A-2H]NADH for NADH resulted in 2-fold and 4-fold decreases in rate for the mitochondrial and cytoplasmic enzymes respectively.", "contents": "Partial reversal of the acetaldehyde and butyraldehyde oxidation reactions catalysed by aldehyde dehydrogenases from sheep liver. In the presence of acetic anhydride or butyric anhydride, liver aldehyde dehydrogenases catalyse the oxidation of NADH at pH 7.0 and 25 degrees C. The maximum velocities and Michaelis constants for NADH at saturating anhydride concentrations are independent of which anhydride is used, the values being V'max. = 12 min-1 and Km for NADH = 9 micrometer for the mitochondrial enzyme and V'max = 25 min-1 and Km for NADH = 20 micrometer for the cytoplasmic enzyme. Substitution of [4A-2H]NADH for NADH resulted in 2-fold and 4-fold decreases in rate for the mitochondrial and cytoplasmic enzymes respectively."}
{"id": "PMID:217350", "title": "Stimulation of intestinal calcium-binding-protein mRNA synthesis in the nucleus of vitamin D-deficient chicks by 1,25-dihydroxycholecalciferol.", "content": "Stimulation of intestinal calcium transport by the hormone 1,25-dihydroxycholecalciferol appears to involve RNA transcriptions and the synthesis of new proteins. Although one of these proteins has been identified as calcium-binding protein, no RNA molecules specifically induced by the hormone in the nucleus have been identified. Nuclear RNA from intestine of vitamin D-deficient chicks before and at various time intervals after treatment with the hormone or cholecalciferol was tested for its ability to code for calcium-binding protein in a cell-free system. Calcium-binding-protein mRNA could only just be detected in the intestinal nuclei 2h after dosing with these steroids which is the same time that it was first observed in the polyribosomes. Thus 1,25-dihydroxycholecalciferol induces the production of new calcium-binding protein by stimulating the formation and rapid release from the nucleus of new mRNA molecules for this protein. Polyribosomal translation of the mRNA continued only as long as it was being synthesized, and the maximum rate of synthesis following a pulse dose of 125ng of the hormone was the same as that observed after prolonged stimulation with cholecalciferol. The possibility that other 1,25-dihydroxycholecalciferol-dependent events may be occurring in the nucleus in the lag period between accumulation of the hormone in the intestine and the appearance of active calcium-binding-protein mRNA, and that these may ultimately control the synthesis of that mRNA, is discussed.", "contents": "Stimulation of intestinal calcium-binding-protein mRNA synthesis in the nucleus of vitamin D-deficient chicks by 1,25-dihydroxycholecalciferol. Stimulation of intestinal calcium transport by the hormone 1,25-dihydroxycholecalciferol appears to involve RNA transcriptions and the synthesis of new proteins. Although one of these proteins has been identified as calcium-binding protein, no RNA molecules specifically induced by the hormone in the nucleus have been identified. Nuclear RNA from intestine of vitamin D-deficient chicks before and at various time intervals after treatment with the hormone or cholecalciferol was tested for its ability to code for calcium-binding protein in a cell-free system. Calcium-binding-protein mRNA could only just be detected in the intestinal nuclei 2h after dosing with these steroids which is the same time that it was first observed in the polyribosomes. Thus 1,25-dihydroxycholecalciferol induces the production of new calcium-binding protein by stimulating the formation and rapid release from the nucleus of new mRNA molecules for this protein. Polyribosomal translation of the mRNA continued only as long as it was being synthesized, and the maximum rate of synthesis following a pulse dose of 125ng of the hormone was the same as that observed after prolonged stimulation with cholecalciferol. The possibility that other 1,25-dihydroxycholecalciferol-dependent events may be occurring in the nucleus in the lag period between accumulation of the hormone in the intestine and the appearance of active calcium-binding-protein mRNA, and that these may ultimately control the synthesis of that mRNA, is discussed."}
{"id": "PMID:217351", "title": "The effect of measuring light photolysis on the kinetics of reaction of reduced cytochrome a3 and carbon monoxide.", "content": "The kinetics of reaction of reduced cytochrome a3 and CO are re-investigated by non-linear optimization techniques. When photolysis by the monitoring light is taken into account, the experimental data are best fitted by a single-intermediate mechanism.", "contents": "The effect of measuring light photolysis on the kinetics of reaction of reduced cytochrome a3 and carbon monoxide. The kinetics of reaction of reduced cytochrome a3 and CO are re-investigated by non-linear optimization techniques. When photolysis by the monitoring light is taken into account, the experimental data are best fitted by a single-intermediate mechanism."}
{"id": "PMID:217352", "title": "A new carbon monoxide-induced complex of cytochrome c oxidase.", "content": "Cytochrome c oxidase isolated from ox heart forms a complex in the presence of millimolar concentrations of CO with absorption bands at 606, 565 and 435 nm (difference spectrum), distinct from both ferrocytochrome a and the classical 590nm carbon-monoxyferrocytochrome a3. This species, which closely resembles Compound C, the derivative formed on photolysis and oxygenation of mixed-valence cytochrome a3+a32+CO, may represent a cytochrome a32+CO complex in which the associated ('invisible') copper is still oxidized.", "contents": "A new carbon monoxide-induced complex of cytochrome c oxidase. Cytochrome c oxidase isolated from ox heart forms a complex in the presence of millimolar concentrations of CO with absorption bands at 606, 565 and 435 nm (difference spectrum), distinct from both ferrocytochrome a and the classical 590nm carbon-monoxyferrocytochrome a3. This species, which closely resembles Compound C, the derivative formed on photolysis and oxygenation of mixed-valence cytochrome a3+a32+CO, may represent a cytochrome a32+CO complex in which the associated ('invisible') copper is still oxidized."}
{"id": "PMID:217353", "title": "The molybdenum centre of native xanthine oxidase. Evidence for proton transfer from substrates to the centre and for existence of an anion-binding site.", "content": "The observation by Bray & Knowles [Proc. R. Soc. London Ser. A (1968) 302, 351--353] of direct transfer, during the catalytic reaction, of hydrogen atoms from substrate molecules to the enzyme xanthine oxidase was reinvestigated. The experimental phenomenon and its basic interpretation were confirmed and extended. In the reduced functional enzyme, molybdenum(V) interacts with two enzyme-bound protons, which are exchangeable with solvent protons. One of these is coupled to the metal with AHav. 1.4mT and the other with AHav. 0.3mT. The molecule also contains a site for the binding of anions, presumably as ligands of molybdenum. This is shown by effects of nitrate ions on the e.p.r. spectra. The spectra of the nitrate and 1-methylxanthine complexes of the reduced enzyme are very similar to one another, and are designated Rapid type-1 spectra. It is concluded that, in the Michaelis complex, the substrate molecule occupies the anion site, probably being bound to molybdenum via the nitrogen in its 9-position. During the turnover process, hydrogen from the substrate C-8 position, after transfer to the enzyme, appears as the proton more strongly coupled to molybdenum. This proton then exchanges with solvent deuterium with a rate constant of 27s-1, at pH 8.2 and 12 degrees C. It has been confirmed that substrate molecules occupying the anion site do not interfere with observation of the transfer and exchange processes.", "contents": "The molybdenum centre of native xanthine oxidase. Evidence for proton transfer from substrates to the centre and for existence of an anion-binding site. The observation by Bray & Knowles [Proc. R. Soc. London Ser. A (1968) 302, 351--353] of direct transfer, during the catalytic reaction, of hydrogen atoms from substrate molecules to the enzyme xanthine oxidase was reinvestigated. The experimental phenomenon and its basic interpretation were confirmed and extended. In the reduced functional enzyme, molybdenum(V) interacts with two enzyme-bound protons, which are exchangeable with solvent protons. One of these is coupled to the metal with AHav. 1.4mT and the other with AHav. 0.3mT. The molecule also contains a site for the binding of anions, presumably as ligands of molybdenum. This is shown by effects of nitrate ions on the e.p.r. spectra. The spectra of the nitrate and 1-methylxanthine complexes of the reduced enzyme are very similar to one another, and are designated Rapid type-1 spectra. It is concluded that, in the Michaelis complex, the substrate molecule occupies the anion site, probably being bound to molybdenum via the nitrogen in its 9-position. During the turnover process, hydrogen from the substrate C-8 position, after transfer to the enzyme, appears as the proton more strongly coupled to molybdenum. This proton then exchanges with solvent deuterium with a rate constant of 27s-1, at pH 8.2 and 12 degrees C. It has been confirmed that substrate molecules occupying the anion site do not interfere with observation of the transfer and exchange processes."}
{"id": "PMID:217354", "title": "Comparison of the molybdenum centres of native and desulpho xanthine oxidase. The nature of the cyanide-labile sulphur atom and the nature of the proton-accepting group.", "content": "The non-functional form of xanthine oxidase known as the desulpho enzyme was compared with the functional enzyme in various ways, to obtain information on the structure of the molybdenum centre and the mechanism of the catalytic reaction. The desulpho enzyme, like the functional one, possesses a site for the binding of anions, presumably as ligands of molybdenum. Evidence is presented that in the Mo(V) e.p.r. signal from the desulpho-enzyme, as in that from the functional enzyme, a weakly coupled proton, in addition to a strongly coupled proton, interacts with the metal. Measurements were carried out by e.p.r. on the rate at which the proton strongly coupled to molybdenum exchanged, on diluting enzyme samples with 2H2O. For the desulpho enzyme the exchange rate constant was 0.40s-1, at pH 8.2 and 12 degrees C, and for the functional enzyme it was 85 s-1. It is shown that the great majority of reported differences between the enzyme forms are consistent with functional enzyme containing an (Enzyme)-Mo=S grouping, replaced in the desulpho form by (Enzyme)-Mo=O. Protonation of these groups, with pK values of about 8 and 10 respectively, would give (Enzyme)-Mo-SH and (Enzyme)-Mo-OH, these being the forms observed by e.p.r. The accepting group in the functional enzyme, for the proton transferred from the substrate while molybdenum is reduced in the catalytic reaction [Gutteridge, Tanner & Bray (1978) Biochem J. 175 869-878], is thus taken to be Mo=S.", "contents": "Comparison of the molybdenum centres of native and desulpho xanthine oxidase. The nature of the cyanide-labile sulphur atom and the nature of the proton-accepting group. The non-functional form of xanthine oxidase known as the desulpho enzyme was compared with the functional enzyme in various ways, to obtain information on the structure of the molybdenum centre and the mechanism of the catalytic reaction. The desulpho enzyme, like the functional one, possesses a site for the binding of anions, presumably as ligands of molybdenum. Evidence is presented that in the Mo(V) e.p.r. signal from the desulpho-enzyme, as in that from the functional enzyme, a weakly coupled proton, in addition to a strongly coupled proton, interacts with the metal. Measurements were carried out by e.p.r. on the rate at which the proton strongly coupled to molybdenum exchanged, on diluting enzyme samples with 2H2O. For the desulpho enzyme the exchange rate constant was 0.40s-1, at pH 8.2 and 12 degrees C, and for the functional enzyme it was 85 s-1. It is shown that the great majority of reported differences between the enzyme forms are consistent with functional enzyme containing an (Enzyme)-Mo=S grouping, replaced in the desulpho form by (Enzyme)-Mo=O. Protonation of these groups, with pK values of about 8 and 10 respectively, would give (Enzyme)-Mo-SH and (Enzyme)-Mo-OH, these being the forms observed by e.p.r. The accepting group in the functional enzyme, for the proton transferred from the substrate while molybdenum is reduced in the catalytic reaction [Gutteridge, Tanner & Bray (1978) Biochem J. 175 869-878], is thus taken to be Mo=S."}
{"id": "PMID:217355", "title": "Kinetic properties of aldehyde dehydrogenase from sheep liver mitochondria.", "content": "The kinetics of the NAD+-dependent oxidation of aldehydes, catalysed by aldehyde dehydrogenase purified from sheep liver mitochondria, were studied in detail. Lag phases were observed in the assays, the length of which were dependent on the enzyme concentration. The measured rates after the lag phase was over were directly proportional to the enzyme concentration. If enzyme was preincubated with NAD+, the lag phase was eliminated. Double-reciprocal plots with aldehyde as the variable substrate were non-linear, showing marked substrate activation. With NAD+ as the variable substrate, double-reciprocal plots were linear, and apparently parallel. Double-reciprocal plots with enzyme modified with disulfiram (tetraethylthiuram disulphide) or iodoacetamide, such that at pH 8.0 the activity was decreased to 50% of the control value, showed no substrate activation, and the plots were linear. At pH 7.0, the kinetic parameters Vmax. and Km NAD+- for the oxidation of acetaldehyde and butyraldehyde by the native enzyme are almost identical. Formaldehyde and propionaldehyde show the same apparent maximum rate. Aldehyde dehydrogenase is able to catalyse the hydrolysis of p-nitrophenyl esters. This esterase activity was stimulated by both NAD+ and NADH, the maximum rate for the NAD+ stimulated esterase reaction being roughly equal to the maximum rate for the oxidation of aldehydes. The mechanistic implications of the above behaviour are discussed.", "contents": "Kinetic properties of aldehyde dehydrogenase from sheep liver mitochondria. The kinetics of the NAD+-dependent oxidation of aldehydes, catalysed by aldehyde dehydrogenase purified from sheep liver mitochondria, were studied in detail. Lag phases were observed in the assays, the length of which were dependent on the enzyme concentration. The measured rates after the lag phase was over were directly proportional to the enzyme concentration. If enzyme was preincubated with NAD+, the lag phase was eliminated. Double-reciprocal plots with aldehyde as the variable substrate were non-linear, showing marked substrate activation. With NAD+ as the variable substrate, double-reciprocal plots were linear, and apparently parallel. Double-reciprocal plots with enzyme modified with disulfiram (tetraethylthiuram disulphide) or iodoacetamide, such that at pH 8.0 the activity was decreased to 50% of the control value, showed no substrate activation, and the plots were linear. At pH 7.0, the kinetic parameters Vmax. and Km NAD+- for the oxidation of acetaldehyde and butyraldehyde by the native enzyme are almost identical. Formaldehyde and propionaldehyde show the same apparent maximum rate. Aldehyde dehydrogenase is able to catalyse the hydrolysis of p-nitrophenyl esters. This esterase activity was stimulated by both NAD+ and NADH, the maximum rate for the NAD+ stimulated esterase reaction being roughly equal to the maximum rate for the oxidation of aldehydes. The mechanistic implications of the above behaviour are discussed."}
{"id": "PMID:217356", "title": "Preparative-scale enzymic synthesis of D-[14C]ribulose 1,5-bisphosphate.", "content": "A procedure is described to prepare uniformly labelled D-[14C]ribulose 1,5-bisphosphate enzymically from uniformly labelled D-[14C]glucose through the coupled reactions catalysed by hexokinase (EC 2.7.1.1), glucose 6-phosphate dehydrogenase (EC 1.1.1.49), 6-phosphogluconate dehydrogenase (EC 1.1.1.44) and 5-phosphoribulokinase (EC 2.7.1.19). All reagents utilized in the method are commercially available. The procedure is a reliable preparative-scale method for synthesizing the dibarium salt of D-[14C]ribulose 1,5-biphosphate with a specific radioactivity up to 7 mCi/mmol and a purity near 90%. The final product was free of other 14C-labelled sugars, sugar phosphate esters, Pi and nucleotides.", "contents": "Preparative-scale enzymic synthesis of D-[14C]ribulose 1,5-bisphosphate. A procedure is described to prepare uniformly labelled D-[14C]ribulose 1,5-bisphosphate enzymically from uniformly labelled D-[14C]glucose through the coupled reactions catalysed by hexokinase (EC 2.7.1.1), glucose 6-phosphate dehydrogenase (EC 1.1.1.49), 6-phosphogluconate dehydrogenase (EC 1.1.1.44) and 5-phosphoribulokinase (EC 2.7.1.19). All reagents utilized in the method are commercially available. The procedure is a reliable preparative-scale method for synthesizing the dibarium salt of D-[14C]ribulose 1,5-biphosphate with a specific radioactivity up to 7 mCi/mmol and a purity near 90%. The final product was free of other 14C-labelled sugars, sugar phosphate esters, Pi and nucleotides."}
{"id": "PMID:217357", "title": "Cartilage proteoglycan aggregates. Electron-microscopic studies of native and fragmented molecules.", "content": "1. Proteoglycan aggregates from bovine nasal cartilage were studied by using electron microscopy of proteoglycan/cytochrome c monolayers. 2. The aggregates contained a variably long central filament of hyaluronic acid with an average length of 1037nm. The proteoglycan monomers attached to the hyaluronic acid appeared as side chain filaments varying in length (averaging 249nm). They were distributed along the central filament at an average distance of about 36nm. 3. Chondroitin sulphate side chains were removed from the proteoglycan monomers of the aggregates by partial chondroitinase digestion. The molecules obtained had the same general appearance as intact aggregates. 4. Proteoglycan aggregates were treated with trypsin and the largest fragment, which contains the hyaluronic acid, link protein and hyaluronic acid-binding region, was recovered and studied with electron microscopy. Filaments that lacked the side chain extensions and had the same length as the central filament in the intact aggregate were observed. 5. Hyaluronic acid isolated after papain digestion of cartilage extracts gave filaments with similar length and size distribution as observed for the central filament both in the intact aggregate and in the trypsin digests. 6. Umbilical-cord hyaluronic acid was also studied and gave electron micrographs similar to those described for hyaluronic acid from cartilage. However, the length of the filament was somewhat shorter. 7. The electron micrographs of both intact and selectively degraded proteoglycans corroborate the current model of cartilage proteoglycan structure.", "contents": "Cartilage proteoglycan aggregates. Electron-microscopic studies of native and fragmented molecules. 1. Proteoglycan aggregates from bovine nasal cartilage were studied by using electron microscopy of proteoglycan/cytochrome c monolayers. 2. The aggregates contained a variably long central filament of hyaluronic acid with an average length of 1037nm. The proteoglycan monomers attached to the hyaluronic acid appeared as side chain filaments varying in length (averaging 249nm). They were distributed along the central filament at an average distance of about 36nm. 3. Chondroitin sulphate side chains were removed from the proteoglycan monomers of the aggregates by partial chondroitinase digestion. The molecules obtained had the same general appearance as intact aggregates. 4. Proteoglycan aggregates were treated with trypsin and the largest fragment, which contains the hyaluronic acid, link protein and hyaluronic acid-binding region, was recovered and studied with electron microscopy. Filaments that lacked the side chain extensions and had the same length as the central filament in the intact aggregate were observed. 5. Hyaluronic acid isolated after papain digestion of cartilage extracts gave filaments with similar length and size distribution as observed for the central filament both in the intact aggregate and in the trypsin digests. 6. Umbilical-cord hyaluronic acid was also studied and gave electron micrographs similar to those described for hyaluronic acid from cartilage. However, the length of the filament was somewhat shorter. 7. The electron micrographs of both intact and selectively degraded proteoglycans corroborate the current model of cartilage proteoglycan structure."}
{"id": "PMID:217358", "title": "Isolation, characterization and distribution of adenosine 3':5'-cyclic monophosphate from Pinus radiata.", "content": "Cyclic AMP was extracted in 0.1 M-HCl from tissues of Pinus radiata and purified by gel filtration on Sephadex G-10, and chromatography on Dowex AG1 (X2) and polyethyleneimine-cellulose in two separate solvent systems. Presumptive cyclic AMP from 10kg batches of pine needles was characterized by countercurrent distribution in the presence of cyclic [8-3H]AMP. Statistical analysis of the curves for radioactivity and mass (determined by the Gilman competitive-binding assay) showed that the fit of the curves was highly significant for seven degrees of freedom. The distribution of cyclic AMP within P. radiata and various other plant tissues was determined by the Gilman procedure. The results suggest that there is no relationship between variations in cyclic AMP concentrations and the known function of the tissue in which it was measured.", "contents": "Isolation, characterization and distribution of adenosine 3':5'-cyclic monophosphate from Pinus radiata. Cyclic AMP was extracted in 0.1 M-HCl from tissues of Pinus radiata and purified by gel filtration on Sephadex G-10, and chromatography on Dowex AG1 (X2) and polyethyleneimine-cellulose in two separate solvent systems. Presumptive cyclic AMP from 10kg batches of pine needles was characterized by countercurrent distribution in the presence of cyclic [8-3H]AMP. Statistical analysis of the curves for radioactivity and mass (determined by the Gilman competitive-binding assay) showed that the fit of the curves was highly significant for seven degrees of freedom. The distribution of cyclic AMP within P. radiata and various other plant tissues was determined by the Gilman procedure. The results suggest that there is no relationship between variations in cyclic AMP concentrations and the known function of the tissue in which it was measured."}
{"id": "PMID:217359", "title": "Hepatic storage of oligosaccharides and glycolipids in a cat affected with GM1 gangliosidosis.", "content": "1. Glycopeptides and glycolipids were isolated from normal cat liver and liver from a cat affected with GM1 gangliosidosis. 2. Bio-Gel P-6 chromatography of the crude glycopeptide fractions demonstrated three major peaks of hexose-containing compounds that were greatly increased in the mutant liver sample; these peaks contained oligosaccharides that comprised over 2% of the liver wet weight. 3. Two of the major pathological oligosaccharides, GP5 and GP6, were purified by chromatography on charcoal/Celite and Sephadex G-25. Oligosaccharides GP5 and GP6 had apparent mol.wts. of 1800 +/- 200 and 1350+/-200 respectively, and contained galactose, mannose and N-acetylglucosamine in molar proportions of 2.0:3.1:4.1 (GP5) and 1.0:2.2:2.7 (GP6). Periodate oxidation studies demonstrated the presence of galactose in a non-reducing terminal position. 4. The neutral glycolipid fraction from the mutant cat liver has a 1.3-fold increase in hexose content accompanied by an increased concentration of asialo-(ganglioside GM1). 5. There was a 2-fold increase of gangliosides in the mutant cat liver compared with normal cats. Ganglioside GM1 and a compound tentatively identified as N-glycolloyl-(ganglioside GM1) were the major glycolipids accumulated.", "contents": "Hepatic storage of oligosaccharides and glycolipids in a cat affected with GM1 gangliosidosis. 1. Glycopeptides and glycolipids were isolated from normal cat liver and liver from a cat affected with GM1 gangliosidosis. 2. Bio-Gel P-6 chromatography of the crude glycopeptide fractions demonstrated three major peaks of hexose-containing compounds that were greatly increased in the mutant liver sample; these peaks contained oligosaccharides that comprised over 2% of the liver wet weight. 3. Two of the major pathological oligosaccharides, GP5 and GP6, were purified by chromatography on charcoal/Celite and Sephadex G-25. Oligosaccharides GP5 and GP6 had apparent mol.wts. of 1800 +/- 200 and 1350+/-200 respectively, and contained galactose, mannose and N-acetylglucosamine in molar proportions of 2.0:3.1:4.1 (GP5) and 1.0:2.2:2.7 (GP6). Periodate oxidation studies demonstrated the presence of galactose in a non-reducing terminal position. 4. The neutral glycolipid fraction from the mutant cat liver has a 1.3-fold increase in hexose content accompanied by an increased concentration of asialo-(ganglioside GM1). 5. There was a 2-fold increase of gangliosides in the mutant cat liver compared with normal cats. Ganglioside GM1 and a compound tentatively identified as N-glycolloyl-(ganglioside GM1) were the major glycolipids accumulated."}
{"id": "PMID:217360", "title": "Simulation of the electron-paramagnetic-resonance spectrum of the iron-protein of nitrogenase. A prediction of the existence of a second paramagnetic centre.", "content": "The e.p.r. spectra of the Fe-proteins of nitrogenase from all sources studied have unusual features in that they have very anisotropic linewidths and low integrated intensities. These characteristics can be explained by assuming that one of the two electrons accepted by these proteins is located at a rapidly relaxing paramagnetic centre that is unobservable by e.p.r., but causes anisotropic broadening of the e.p.r. signal of the other electron. Complex-formation between Fe-proteins and MgATP is described in terms of a 50-60 degrees rotation of the e.p.r.-observable centre.", "contents": "Simulation of the electron-paramagnetic-resonance spectrum of the iron-protein of nitrogenase. A prediction of the existence of a second paramagnetic centre. The e.p.r. spectra of the Fe-proteins of nitrogenase from all sources studied have unusual features in that they have very anisotropic linewidths and low integrated intensities. These characteristics can be explained by assuming that one of the two electrons accepted by these proteins is located at a rapidly relaxing paramagnetic centre that is unobservable by e.p.r., but causes anisotropic broadening of the e.p.r. signal of the other electron. Complex-formation between Fe-proteins and MgATP is described in terms of a 50-60 degrees rotation of the e.p.r.-observable centre."}
{"id": "PMID:217361", "title": "Malate dehydrogenase of the cytosol. A kinetic investigation of the reaction mechanism and a comparison with lactate dehydrogenase.", "content": "1. The mechanisms of the reduction of oxaloacetate and of 3-fluoro-oxaloacetate by NADH catalysed by cytoplasmic pig heart malate dehydrogenase (MDH) were investigated. 2. One mol of dimeric enzyme produces 1.7+/-0.4 mol of enzyme-bound NADH when mixed with saturating NAD+ and L-malate at a rate much higher than the subsequent turnover at pH 7.5. 3. Transient measurements of protein and nucleotide fluorescence show that the steady-state complex in the forward direction is MDH-NADH and in the reverse direction MDH-NADH-oxaloacetate. 4. The rate of dissociation of MDH-NADH was measured and is the same as Vmax. in the forward direction at pH 7.5. Both NADH-binding sites are kinetically equivalent. The rate of dissociation varies with pH, as does the equilibrium binding constant for NADH. 5. 3-Fluoro-oxaloacetate is composed of three forms (F1, F2 and S) of which F1 and F2 are immediately substrates for the enzyme. The third form, S, is not a substrate, but when the F forms are used up form S slowly and non-enzymically equilibrates to yield the active substrate forms. S is 2,2-dihydroxy-3-fluorosuccinate. 6. The steady-state compound during the reduction of form F1 is an enzyme form that does not contain NADH, probably MDH-NAD+-fluoromalate. The steady-state compound for form F2 is an enzyme form containing NADH, probably MDH-NADH-fluoro-oxaloacetate. 7. The rate-limiting reaction in the reduction of form F2 shows a deuterium isotope rate ratio of 4 when NADH is replaced by its deuterium analogue, and the rate-limiting reaction is concluded to be hydride transfer. 8. A novel titration was used to show that dimeric cytoplasmic malate dehydrogenase contains two sites that can rapidly reduce the F1 form of 3-fluoro-oxaloacetate. The enzyme shows 'all-of-the-sites' behaviour. 9. Partial mechanisms are proposed to explain the enzyme-catalysed transformations of the natural and the fluoro substrates. These mechanisms are similar to the mechanism of pig heart lactate dehydrogenase and this, and the structural results of others, can be explained if the two enzymes are a product of divergent evolution.", "contents": "Malate dehydrogenase of the cytosol. A kinetic investigation of the reaction mechanism and a comparison with lactate dehydrogenase. 1. The mechanisms of the reduction of oxaloacetate and of 3-fluoro-oxaloacetate by NADH catalysed by cytoplasmic pig heart malate dehydrogenase (MDH) were investigated. 2. One mol of dimeric enzyme produces 1.7+/-0.4 mol of enzyme-bound NADH when mixed with saturating NAD+ and L-malate at a rate much higher than the subsequent turnover at pH 7.5. 3. Transient measurements of protein and nucleotide fluorescence show that the steady-state complex in the forward direction is MDH-NADH and in the reverse direction MDH-NADH-oxaloacetate. 4. The rate of dissociation of MDH-NADH was measured and is the same as Vmax. in the forward direction at pH 7.5. Both NADH-binding sites are kinetically equivalent. The rate of dissociation varies with pH, as does the equilibrium binding constant for NADH. 5. 3-Fluoro-oxaloacetate is composed of three forms (F1, F2 and S) of which F1 and F2 are immediately substrates for the enzyme. The third form, S, is not a substrate, but when the F forms are used up form S slowly and non-enzymically equilibrates to yield the active substrate forms. S is 2,2-dihydroxy-3-fluorosuccinate. 6. The steady-state compound during the reduction of form F1 is an enzyme form that does not contain NADH, probably MDH-NAD+-fluoromalate. The steady-state compound for form F2 is an enzyme form containing NADH, probably MDH-NADH-fluoro-oxaloacetate. 7. The rate-limiting reaction in the reduction of form F2 shows a deuterium isotope rate ratio of 4 when NADH is replaced by its deuterium analogue, and the rate-limiting reaction is concluded to be hydride transfer. 8. A novel titration was used to show that dimeric cytoplasmic malate dehydrogenase contains two sites that can rapidly reduce the F1 form of 3-fluoro-oxaloacetate. The enzyme shows 'all-of-the-sites' behaviour. 9. Partial mechanisms are proposed to explain the enzyme-catalysed transformations of the natural and the fluoro substrates. These mechanisms are similar to the mechanism of pig heart lactate dehydrogenase and this, and the structural results of others, can be explained if the two enzymes are a product of divergent evolution."}
{"id": "PMID:217362", "title": "Studies on the fate of pulmonary surfactant in the lung.", "content": "1. Radioactively labelled pulmonary surfactant was prepared in an isolated perfused lung system provided with [14C]hexadecanoate. 2. After intratracheal administration of pulmonary surfactant radioactively labelled components were rapidly distributed into different lung fractions, including macrophages (free cells), but most of the radioactive label was accumulated by the lung tissue. 3. Alveolar macrophages, maintained in a variety of culture media in the presence and absence of mineral particles, incorporated a low percentage (11%) of radioactively labelled components when incubated with the surfactant, although evolution of labelled CO2 (6% of the original total activity) suggested that some breakdown of the components had taken place. 4. In similar cultures little intracellular accumulation or extracellular release of non-esterified fatty acids was demonstrated, indicating minimal catabolism of the high-molecular-weight lipid components of surfactant (particularly phosphatidylcholine). 5. However, experiments in vitro designed to simulate the lysosomal degradation of endocytosed surfactant indicated that the macrophage had enzymes capable of releasing non-esterified fatty acids, particularly hexadecanoate, from the lipoprotein complex. 6. It is argued that lung cells, other than alveolar macrophages, may also have a role in surfactant turnover.", "contents": "Studies on the fate of pulmonary surfactant in the lung. 1. Radioactively labelled pulmonary surfactant was prepared in an isolated perfused lung system provided with [14C]hexadecanoate. 2. After intratracheal administration of pulmonary surfactant radioactively labelled components were rapidly distributed into different lung fractions, including macrophages (free cells), but most of the radioactive label was accumulated by the lung tissue. 3. Alveolar macrophages, maintained in a variety of culture media in the presence and absence of mineral particles, incorporated a low percentage (11%) of radioactively labelled components when incubated with the surfactant, although evolution of labelled CO2 (6% of the original total activity) suggested that some breakdown of the components had taken place. 4. In similar cultures little intracellular accumulation or extracellular release of non-esterified fatty acids was demonstrated, indicating minimal catabolism of the high-molecular-weight lipid components of surfactant (particularly phosphatidylcholine). 5. However, experiments in vitro designed to simulate the lysosomal degradation of endocytosed surfactant indicated that the macrophage had enzymes capable of releasing non-esterified fatty acids, particularly hexadecanoate, from the lipoprotein complex. 6. It is argued that lung cells, other than alveolar macrophages, may also have a role in surfactant turnover."}
{"id": "PMID:217363", "title": "Effects of cholera toxin and guanosine 5'-[betagamma-imido]triphosphate on beta-adrenergic-receptor affinity.", "content": "A comparison was made of the effects of cholera toxin and p[NH]ppG on the binding affinity of beta-adrenergic receptors in toad erythrocyte membranes. This was determined by studying the ability of isoproterenol and propranolol to compete for the receptor with (-)-[3H]dihydroalprenolol. p[NH]ppG decreased the receptor affinity for the agonist isoproterenol (i.e. a 'right' shift in the displacement-concentration curve), but was without effect on the affinity for the antagonist propranolol. Toad erythrocyte membranes after treatment with cholera toxin exhibited increased receptor affinity for isoproterenol (i.e. a 'left' shift in the displacement curve), but did not affect the affinity for propranolol. p[NH[ppG was able to exert its right shift even in cholera-toxin treated membranes. The ability of cholera toxin to alter beta-adrenergic-receptor affinity is interpreted as further evidence that the toxin affects the nucleotide-regulatory component of adenylate cyclase. The regulatory component affected may be the catecholamine-sensitive guanosine triphosphatase.", "contents": "Effects of cholera toxin and guanosine 5'-[betagamma-imido]triphosphate on beta-adrenergic-receptor affinity. A comparison was made of the effects of cholera toxin and p[NH]ppG on the binding affinity of beta-adrenergic receptors in toad erythrocyte membranes. This was determined by studying the ability of isoproterenol and propranolol to compete for the receptor with (-)-[3H]dihydroalprenolol. p[NH]ppG decreased the receptor affinity for the agonist isoproterenol (i.e. a 'right' shift in the displacement-concentration curve), but was without effect on the affinity for the antagonist propranolol. Toad erythrocyte membranes after treatment with cholera toxin exhibited increased receptor affinity for isoproterenol (i.e. a 'left' shift in the displacement curve), but did not affect the affinity for propranolol. p[NH[ppG was able to exert its right shift even in cholera-toxin treated membranes. The ability of cholera toxin to alter beta-adrenergic-receptor affinity is interpreted as further evidence that the toxin affects the nucleotide-regulatory component of adenylate cyclase. The regulatory component affected may be the catecholamine-sensitive guanosine triphosphatase."}
{"id": "PMID:217364", "title": "Calcium-activated hydrolysis of phosphatidyl-myo-inositol 4-phosphate and phosphatidyl-myo-inositol 4,5-bisphosphate in guinea-pig synaptosomes.", "content": "1. Addition of the bivalent ionophore A23187 to synaptosomes isolated from guinea-pig brain cortex and labelled with [(32)P]phosphate in vitro or in vivo caused a marked loss of radioactivity from phosphatidyl-myo-inositol 4-phosphate (diphosphoinositide) and phosphatidyl-myo-inositol 4,5-bisphosphate (triphosphoinositide) and stimulated labelling of phosphatidate. No change occurred in the labelling of other phospholipids. 2. In conditions that minimized changes in internal Mg(2+) concentrations, the effect of ionophore A23187 on labelling of synaptosomal di- and tri-phosphoinositide was dependent on Ca(2+) and was apparent at Ca(2+) concentrations in the medium as low as 10(-5)m. 3. An increase in internal Mg(2+) concentration stimulated incorporation of [(32)P]phosphate into di- and tri-phosphoinositide, whereas lowering internal Mg(2+) decreased labelling. 4. Increased labelling of phosphatidate was independent of medium Mg(2+) concentration and apparently only partly dependent on medium Ca(2+) concentration. 5. The loss of label from di- and tri-phosphoinositide caused by ionophore A23187 was accompanied by losses in the amounts of both lipids. 6. Addition of excess of EGTA to synaptosomes treated with ionophore A23187 in the presence of Ca(2+) caused a rapid resynthesis of di- and tri-phosphoinositide and a further stimulation of phosphatidate labelling. 7. Addition of ionophore A23187 to synaptosomes labelled in vivo with [(3)H]inositol caused a significant loss of label from di- and tri-phosphoinositide, but not from phosphatidylinositol. There was a considerable rise in labelling of inositol diphosphate, a small increase in that of inositol phosphate, but no significant production of inositol triphosphate. 8. (32)P-labelled di- and tri-phosphoinositides appeared to be located in the synaptosomal plasma membrane. 9. The results indicate that increased Ca(2+) influx into synaptosomes markedly activates triphosphoinositide phosphatase and diphosphoinositide phosphodiesterase, but has little or no effect on phosphatidylinositol phosphodiesterase.", "contents": "Calcium-activated hydrolysis of phosphatidyl-myo-inositol 4-phosphate and phosphatidyl-myo-inositol 4,5-bisphosphate in guinea-pig synaptosomes. 1. Addition of the bivalent ionophore A23187 to synaptosomes isolated from guinea-pig brain cortex and labelled with [(32)P]phosphate in vitro or in vivo caused a marked loss of radioactivity from phosphatidyl-myo-inositol 4-phosphate (diphosphoinositide) and phosphatidyl-myo-inositol 4,5-bisphosphate (triphosphoinositide) and stimulated labelling of phosphatidate. No change occurred in the labelling of other phospholipids. 2. In conditions that minimized changes in internal Mg(2+) concentrations, the effect of ionophore A23187 on labelling of synaptosomal di- and tri-phosphoinositide was dependent on Ca(2+) and was apparent at Ca(2+) concentrations in the medium as low as 10(-5)m. 3. An increase in internal Mg(2+) concentration stimulated incorporation of [(32)P]phosphate into di- and tri-phosphoinositide, whereas lowering internal Mg(2+) decreased labelling. 4. Increased labelling of phosphatidate was independent of medium Mg(2+) concentration and apparently only partly dependent on medium Ca(2+) concentration. 5. The loss of label from di- and tri-phosphoinositide caused by ionophore A23187 was accompanied by losses in the amounts of both lipids. 6. Addition of excess of EGTA to synaptosomes treated with ionophore A23187 in the presence of Ca(2+) caused a rapid resynthesis of di- and tri-phosphoinositide and a further stimulation of phosphatidate labelling. 7. Addition of ionophore A23187 to synaptosomes labelled in vivo with [(3)H]inositol caused a significant loss of label from di- and tri-phosphoinositide, but not from phosphatidylinositol. There was a considerable rise in labelling of inositol diphosphate, a small increase in that of inositol phosphate, but no significant production of inositol triphosphate. 8. (32)P-labelled di- and tri-phosphoinositides appeared to be located in the synaptosomal plasma membrane. 9. The results indicate that increased Ca(2+) influx into synaptosomes markedly activates triphosphoinositide phosphatase and diphosphoinositide phosphodiesterase, but has little or no effect on phosphatidylinositol phosphodiesterase."}
{"id": "PMID:217365", "title": "A method for measuring relative changes in guanosine 3':5'-cyclic monophosphate in mouse neuroblastoma cells on muscarinic cholinergic stimulation.", "content": "A convenient, inexpensive assay was developed for measuring relative changes in cyclic GMP in whole mouse neuroblastoma cells (clone NIE 115) based on labelling the cellular GTP pool with [8(-3)H]guanine. The time course of cell labelling and the distribution of radioactivity among possible products were studied; GTP is the only major labelled species. Radioactive cyclic GMP produced from the radioactive GTP on cell stimulation is isolated by column chromatography nad its identity has been rigorously established by paper chromatography and ion-exchange chromatography. The assay was used to study the time course of the cyclic GMP changes that occur after stimulation of neuroblastoma cells with carbamoylcholine and the dependence of the cyclic GMP changes on the carbamoylcholine concentration. The assay gives results comparable with those obtained by using a radioimmunoassay for cyclic GMP and should be applicable to other whole-cell and tissue-slice systems.", "contents": "A method for measuring relative changes in guanosine 3':5'-cyclic monophosphate in mouse neuroblastoma cells on muscarinic cholinergic stimulation. A convenient, inexpensive assay was developed for measuring relative changes in cyclic GMP in whole mouse neuroblastoma cells (clone NIE 115) based on labelling the cellular GTP pool with [8(-3)H]guanine. The time course of cell labelling and the distribution of radioactivity among possible products were studied; GTP is the only major labelled species. Radioactive cyclic GMP produced from the radioactive GTP on cell stimulation is isolated by column chromatography nad its identity has been rigorously established by paper chromatography and ion-exchange chromatography. The assay was used to study the time course of the cyclic GMP changes that occur after stimulation of neuroblastoma cells with carbamoylcholine and the dependence of the cyclic GMP changes on the carbamoylcholine concentration. The assay gives results comparable with those obtained by using a radioimmunoassay for cyclic GMP and should be applicable to other whole-cell and tissue-slice systems."}
{"id": "PMID:217366", "title": "Recognition of the beta-subunit of human chorionic gonadotropin and sub-determinants by target tissue receptors.", "content": "The beta-subunit of human chorionic gonadotropin, purified immunochemically to eliminate undissociated human chorionic gonadotropin, induced testosterone production by mouse Leydig cells at concentrations 400-fold higher than human chorionic gonadotropin. Steroidogenesis was also stimulated by a synthetic fragment of the beta-subunit of human chorionic gonadotropin conforming to the peptide sequence residues 39--71, whereas peptide sequence residues 39--56 and three C-terminal fragments (residues 115--145, 111--145 and 101--145) failed to cause steroidogenesis. These studies suggest the presence in the beta-subunit of human chorionic gonadotropin of determinants recognized by the tissue receptors, a part of these determinants residing between amino acid residues 57--71.", "contents": "Recognition of the beta-subunit of human chorionic gonadotropin and sub-determinants by target tissue receptors. The beta-subunit of human chorionic gonadotropin, purified immunochemically to eliminate undissociated human chorionic gonadotropin, induced testosterone production by mouse Leydig cells at concentrations 400-fold higher than human chorionic gonadotropin. Steroidogenesis was also stimulated by a synthetic fragment of the beta-subunit of human chorionic gonadotropin conforming to the peptide sequence residues 39--71, whereas peptide sequence residues 39--56 and three C-terminal fragments (residues 115--145, 111--145 and 101--145) failed to cause steroidogenesis. These studies suggest the presence in the beta-subunit of human chorionic gonadotropin of determinants recognized by the tissue receptors, a part of these determinants residing between amino acid residues 57--71."}
{"id": "PMID:217367", "title": "Rat adipose-tissue glycerol phosphate acyltransferase can be inactivated by cyclic AMP-dependent protein kinase.", "content": "Rat adipose-tissue glycerol phosphate acyltransferase can be inactivated in a phosphorylation reaction catalysed by cyclic AMP-dependent protein kinase and reactivated by treatment with alkaline phosphatase. These results suggest that phosphorylation of glycerol phosphate acyltransferase may be involved in the hormonal control of esterification.", "contents": "Rat adipose-tissue glycerol phosphate acyltransferase can be inactivated by cyclic AMP-dependent protein kinase. Rat adipose-tissue glycerol phosphate acyltransferase can be inactivated in a phosphorylation reaction catalysed by cyclic AMP-dependent protein kinase and reactivated by treatment with alkaline phosphatase. These results suggest that phosphorylation of glycerol phosphate acyltransferase may be involved in the hormonal control of esterification."}
{"id": "PMID:217368", "title": "The role of phosphoenolpyruvate carboxykinase in amino acid metabolism in muscle.", "content": "Starvation or feeding rats on a high-protein diet, valine or isoleucine, but not leucine, increases the activity of muscle phosphoenolpyruvate carboxykinase, but has no effect on NADP+-linked malate dehydrogenase. This suggests that muscle phosphoenolpyruvate carboxykinase is involved in oxidation or conversion of some amino acids to alanine.", "contents": "The role of phosphoenolpyruvate carboxykinase in amino acid metabolism in muscle. Starvation or feeding rats on a high-protein diet, valine or isoleucine, but not leucine, increases the activity of muscle phosphoenolpyruvate carboxykinase, but has no effect on NADP+-linked malate dehydrogenase. This suggests that muscle phosphoenolpyruvate carboxykinase is involved in oxidation or conversion of some amino acids to alanine."}
{"id": "PMID:217369", "title": "Control of phosphatidylcholine synthesis and the regulatory role of choline kinase in rat liver. Evidence from essential-fatty acid-deficient rats.", "content": "Choline kinase and phosphocholine cytidylytransferase catalyse the rate-limiting steps of the cytidine pathway for the synthesis of phosphatidylcholine [Infante (1977) Biochem. J. 167, 847--849]. Essential-fatty acid deficiency induces a 3.5-fold increase in the specific activity of choline kinase, whereas the specific activity of the cytidylytransferase remains unchanged in rat liver. This change in specific activity accounts for the calculated increase in flux through the cytidine pathway produced in vivo by the same dietary state [Trewhella & Collins (1973 Biochim. Biophys. Acta 296, 34--50], thus confirming the fact that choline kinase has a regulatory role in the cytidine pathway for the synthesis of phosphatidylcholine.", "contents": "Control of phosphatidylcholine synthesis and the regulatory role of choline kinase in rat liver. Evidence from essential-fatty acid-deficient rats. Choline kinase and phosphocholine cytidylytransferase catalyse the rate-limiting steps of the cytidine pathway for the synthesis of phosphatidylcholine [Infante (1977) Biochem. J. 167, 847--849]. Essential-fatty acid deficiency induces a 3.5-fold increase in the specific activity of choline kinase, whereas the specific activity of the cytidylytransferase remains unchanged in rat liver. This change in specific activity accounts for the calculated increase in flux through the cytidine pathway produced in vivo by the same dietary state [Trewhella & Collins (1973 Biochim. Biophys. Acta 296, 34--50], thus confirming the fact that choline kinase has a regulatory role in the cytidine pathway for the synthesis of phosphatidylcholine."}
{"id": "PMID:217393", "title": "Inhibition of collagen gelation by action of the superoxide radical.", "content": "Superoxide anion, a highly reactive free radical, was generated in vitro using enriched purified xanthine oxidase. Collagen solutions exposed to superoxide radical failed to gel normally when heated to 37 degrees C. The magnitude of the inhibition of gelation was propotional to duration of exposure and to flux of superoxide. Since inhibition of collagen gelation reflects alteration of collagen biochemistry, and/or collagen degradation, it is suggested that the action of free radicals produced in vivo by leukocytes may adversely affect the structural or functional integrity of cartilage and adjacent joint structures.", "contents": "Inhibition of collagen gelation by action of the superoxide radical. Superoxide anion, a highly reactive free radical, was generated in vitro using enriched purified xanthine oxidase. Collagen solutions exposed to superoxide radical failed to gel normally when heated to 37 degrees C. The magnitude of the inhibition of gelation was propotional to duration of exposure and to flux of superoxide. Since inhibition of collagen gelation reflects alteration of collagen biochemistry, and/or collagen degradation, it is suggested that the action of free radicals produced in vivo by leukocytes may adversely affect the structural or functional integrity of cartilage and adjacent joint structures."}
{"id": "PMID:217394", "title": "[Radiotherapy of carcinoma of the nasopharynz: clinical results (author's transl)].", "content": "A series of 64 patients with malignant tumours of the nasopharynx treated by cobalt irradiation is analyzed. The crude 5-year survival rate for the entire epithelial group was 32%; 55% for N- group, 25% for N+. Treatment methods avoiding complications are discussed.", "contents": "[Radiotherapy of carcinoma of the nasopharynz: clinical results (author's transl)]. A series of 64 patients with malignant tumours of the nasopharynx treated by cobalt irradiation is analyzed. The crude 5-year survival rate for the entire epithelial group was 32%; 55% for N- group, 25% for N+. Treatment methods avoiding complications are discussed."}
{"id": "PMID:217399", "title": "Specificity of the inhibition of DNA synthesis by extracts from cloned normal, sarcoma-virus-transformed and revertant 3T3 cells.", "content": "Extracts containing tissue-specific DNA-inhibitory activity were prepared from normal FL (Swiss) and BALBc3T3 cells, from these cells transformed with sarcoma virus and from revertants cloned from the transformed cell lines. By testing all extracts on all cell lines we found that (1) production of and susceptibility to the inhibitors were decreased in transformed BALB/c cells (2) specificity varied with expression of the transforming genome, as an extract from a given cell line inhibited the growth of its cell of origin, e.g. revertant, more than normal or transformed cells, and (3) there was also a DNA-synthesis stimulator.", "contents": "Specificity of the inhibition of DNA synthesis by extracts from cloned normal, sarcoma-virus-transformed and revertant 3T3 cells. Extracts containing tissue-specific DNA-inhibitory activity were prepared from normal FL (Swiss) and BALBc3T3 cells, from these cells transformed with sarcoma virus and from revertants cloned from the transformed cell lines. By testing all extracts on all cell lines we found that (1) production of and susceptibility to the inhibitors were decreased in transformed BALB/c cells (2) specificity varied with expression of the transforming genome, as an extract from a given cell line inhibited the growth of its cell of origin, e.g. revertant, more than normal or transformed cells, and (3) there was also a DNA-synthesis stimulator."}
{"id": "PMID:217398", "title": "Effects of Corynebacterium parvum on murine myeloid leukaemia.", "content": "The effects of C. parvum on RFM/UN myeloid leukaemia were studied. Mice inoculated with 7.0 mg but not 0.7 mg C. parvum i.p. survived significantly longer than untreated leukaemic mice (P less than 0.001). Administration of silica abrogated the effects of C. parvum, whilst polyvinyl pyridine-N-oxide prevented the inhibitory effects of silica. These studies demonstrate that a single large dose of C. parvum, either before or after leukaemic-cell passage, can significantly prolong the survival of RFM mice bearing myeloid leukaemia. The effects of silica and PVNO on C. parvum suggest a critical role for macrophages in C. parvum effects on myeloid leukaemia.", "contents": "Effects of Corynebacterium parvum on murine myeloid leukaemia. The effects of C. parvum on RFM/UN myeloid leukaemia were studied. Mice inoculated with 7.0 mg but not 0.7 mg C. parvum i.p. survived significantly longer than untreated leukaemic mice (P less than 0.001). Administration of silica abrogated the effects of C. parvum, whilst polyvinyl pyridine-N-oxide prevented the inhibitory effects of silica. These studies demonstrate that a single large dose of C. parvum, either before or after leukaemic-cell passage, can significantly prolong the survival of RFM mice bearing myeloid leukaemia. The effects of silica and PVNO on C. parvum suggest a critical role for macrophages in C. parvum effects on myeloid leukaemia."}
{"id": "PMID:217400", "title": "Effect of prostaglandins and hormones on cyclic AMP formation in rat hepatomas and liver tissue.", "content": "The formation of cyclic AMP was studied in normal liver, subcutaneous hepatomas derived from MH1C1 cells, and premalignant liver and primary hepatomas induced by the carcinogens 2-acetylaminofluorene (AAF) and 4-dimethylamino-azobenzene (DAB). While only very slight effects of prostaglandins (PG) were seen in slices of normal liver, all the hepatomas responded strongly to PGE1 and PGE2. The hepatomas also had increase PGE1-sensitive adenylate-cyclase activity. PGF1alpha and PGF2alpha did not increase the cAMP level significantly either in the liver or in the hepatomas. During AAF carcinogenesis the response to PGE1 increased slightly during the carcinogen feeding, and was greatly elevated only in the fully developed hepatomas. This is in contrast to the increase in adrenalin response seen during carcinogenesis, which starts much earlier, and reaches a peak value within 8--10 weeks. It is concluded that various hepatomas have elevated responsiveness to PGE1 and PGE2 as well as to adrenalin, but the course of change in the tissues' ability to respond to these agents during carcinogenesis is very different.", "contents": "Effect of prostaglandins and hormones on cyclic AMP formation in rat hepatomas and liver tissue. The formation of cyclic AMP was studied in normal liver, subcutaneous hepatomas derived from MH1C1 cells, and premalignant liver and primary hepatomas induced by the carcinogens 2-acetylaminofluorene (AAF) and 4-dimethylamino-azobenzene (DAB). While only very slight effects of prostaglandins (PG) were seen in slices of normal liver, all the hepatomas responded strongly to PGE1 and PGE2. The hepatomas also had increase PGE1-sensitive adenylate-cyclase activity. PGF1alpha and PGF2alpha did not increase the cAMP level significantly either in the liver or in the hepatomas. During AAF carcinogenesis the response to PGE1 increased slightly during the carcinogen feeding, and was greatly elevated only in the fully developed hepatomas. This is in contrast to the increase in adrenalin response seen during carcinogenesis, which starts much earlier, and reaches a peak value within 8--10 weeks. It is concluded that various hepatomas have elevated responsiveness to PGE1 and PGE2 as well as to adrenalin, but the course of change in the tissues' ability to respond to these agents during carcinogenesis is very different."}
{"id": "PMID:217401", "title": "Inherited aplastic anaemia with increased endoreduplications: a new syndrome of Fanconi's anaemia variant?", "content": "Two sisters with aplastic anaemia without other congenital anomalies are described. Peripheral blood cytogenetic studies revealed an increase in endoreduplications in the absence of other unstable chromosome anomalies. Increased expression of T-antigen following SV40 virus infection in vitro was demonstrated in both sisters, as well as other normal family members. We feel that these patients represent a variant of Fanconi's anaemia. The importance of performing chromosome studies in idiopathic aplastic anaemia is emphasized.", "contents": "Inherited aplastic anaemia with increased endoreduplications: a new syndrome of Fanconi's anaemia variant? Two sisters with aplastic anaemia without other congenital anomalies are described. Peripheral blood cytogenetic studies revealed an increase in endoreduplications in the absence of other unstable chromosome anomalies. Increased expression of T-antigen following SV40 virus infection in vitro was demonstrated in both sisters, as well as other normal family members. We feel that these patients represent a variant of Fanconi's anaemia. The importance of performing chromosome studies in idiopathic aplastic anaemia is emphasized."}
{"id": "PMID:217404", "title": "Structure of the dimyristoylphosphatidylcholine vesicle and the complex formed by its interaction with apolipoprotein C-III: X-ray small-angle scattering studies.", "content": "Single bilayer vesicles of dimyristoylphosphatidylcholine have been investigated by small-angle X-ray scattering at 28 degrees C. The results indicate that these vesicles are hollow spherical shell structures with an outer radius of approximately 12 nm and a molecular weight of (3.2 +/- 0.5) X 10(6). The shell was found to be 4.4 +/- 0.2 nm thick with a cross-sectional electron-density profile characteristic for a single phospholipid bilayer. Upon interaction of these vesicles with apolipoprotein C-III from human very low density lipoproteins at a protein/lipid ratio greater than 0.08 (g/g), a complex containing 0.25 g of protein/g of lipid, with molecular weight of (3.9 +/- 0.4) X 10(5), is formed. The shape analysis indicates a highly asymmetric particle with an internal partition of low and high electron density resembling that produced by a bilayer structure. Model calculations and curve-fitting procedures show good agreement between the experimental scattering curve and that computed for an oblate ellipsoidal structure with dimensions of 17 X 17 X 5 nm and a 1 nm thick shell of high electron density surrounding the core of low electron density.", "contents": "Structure of the dimyristoylphosphatidylcholine vesicle and the complex formed by its interaction with apolipoprotein C-III: X-ray small-angle scattering studies. Single bilayer vesicles of dimyristoylphosphatidylcholine have been investigated by small-angle X-ray scattering at 28 degrees C. The results indicate that these vesicles are hollow spherical shell structures with an outer radius of approximately 12 nm and a molecular weight of (3.2 +/- 0.5) X 10(6). The shell was found to be 4.4 +/- 0.2 nm thick with a cross-sectional electron-density profile characteristic for a single phospholipid bilayer. Upon interaction of these vesicles with apolipoprotein C-III from human very low density lipoproteins at a protein/lipid ratio greater than 0.08 (g/g), a complex containing 0.25 g of protein/g of lipid, with molecular weight of (3.9 +/- 0.4) X 10(5), is formed. The shape analysis indicates a highly asymmetric particle with an internal partition of low and high electron density resembling that produced by a bilayer structure. Model calculations and curve-fitting procedures show good agreement between the experimental scattering curve and that computed for an oblate ellipsoidal structure with dimensions of 17 X 17 X 5 nm and a 1 nm thick shell of high electron density surrounding the core of low electron density."}
{"id": "PMID:217406", "title": "Cation-induced regulatory mechanism of GTPase activity dependent on polypeptide initiation factor 2.", "content": "Initiation factor IF-2 ribosome dependent GTP hydrolysis (uncoupled GTPase) presents a bell-shaped pH profile which is shifted by changes in ionic strength. At low ionic strength (I = 25 mM) the maximal hydrolytic activity occurs at pH 7.5; when the ionic strength is increased the pH optimum of the reaction is shifted toward more acidic values. Such behavior can be satisfactorily explained as the effect of an electrostatic potential developed by a neighboring polyanion, presumably RNA, on the catalytic site. The addition of fMet-tRNAfMet or AcPhe-tRNAPhe and messenger RNA (coupled GTPase) changes the ionic strength--pH characteristics of the reaction. Thus there is an effect, direct or indirect, of components located at the ribosomal P site. Investigation of the effect of neighboring polyanions on the catalytic activity of the factor-dependent ribosomal GTPases can be seen to provide information about their functional significance that is complementary to that gained from direct structural studies.", "contents": "Cation-induced regulatory mechanism of GTPase activity dependent on polypeptide initiation factor 2. Initiation factor IF-2 ribosome dependent GTP hydrolysis (uncoupled GTPase) presents a bell-shaped pH profile which is shifted by changes in ionic strength. At low ionic strength (I = 25 mM) the maximal hydrolytic activity occurs at pH 7.5; when the ionic strength is increased the pH optimum of the reaction is shifted toward more acidic values. Such behavior can be satisfactorily explained as the effect of an electrostatic potential developed by a neighboring polyanion, presumably RNA, on the catalytic site. The addition of fMet-tRNAfMet or AcPhe-tRNAPhe and messenger RNA (coupled GTPase) changes the ionic strength--pH characteristics of the reaction. Thus there is an effect, direct or indirect, of components located at the ribosomal P site. Investigation of the effect of neighboring polyanions on the catalytic activity of the factor-dependent ribosomal GTPases can be seen to provide information about their functional significance that is complementary to that gained from direct structural studies."}
{"id": "PMID:217412", "title": "Cyclic nucleotide dependent protein kinase and the phosphorylation of endogenous proteins of retinal rod outer segments.", "content": "Cyclic nucleotide dependent protein kinase has been extracted wiht Tris or Lubrol PX from purified rod outer segments (ROS) of bovine retina. The activity of the enzyme is unaffected by light but is stimulated by either cyclic guanosine 3',5'-monophosphate (cGMP) or cyclic adenosine 3',5'-monophosphate (cAMP). Most of the solubilized enzyme elutes from DEAE-cellulose with about 0.18 M NaCl (type II protein kinase). An endogenous 30,000 molecular weight protein of the soluble fraction of ROS as well as exogenous histone are phosphorylated by the protein kinase in a cyclic nucleotide dependent manner. The Tris-extracted enzyme can be reassociated in the presence of Mg2+ with ROS membranes that are depleted of protein kinase activity. The reassociated protein kinase is insensitive to exogenous cyclic nucleotides, and it catalyzes the phosphorylation of the membrane protein, bleached rhodopsin. While the soluble and membrane-associated protein kinases may be interchangeable, they appear to be modulated by different biological signals; soluble protein kinase activity is increased by cyclic nucleotides whereas membrane-bound activity is enhanced when rhodopsin is bleached by light.", "contents": "Cyclic nucleotide dependent protein kinase and the phosphorylation of endogenous proteins of retinal rod outer segments. Cyclic nucleotide dependent protein kinase has been extracted wiht Tris or Lubrol PX from purified rod outer segments (ROS) of bovine retina. The activity of the enzyme is unaffected by light but is stimulated by either cyclic guanosine 3',5'-monophosphate (cGMP) or cyclic adenosine 3',5'-monophosphate (cAMP). Most of the solubilized enzyme elutes from DEAE-cellulose with about 0.18 M NaCl (type II protein kinase). An endogenous 30,000 molecular weight protein of the soluble fraction of ROS as well as exogenous histone are phosphorylated by the protein kinase in a cyclic nucleotide dependent manner. The Tris-extracted enzyme can be reassociated in the presence of Mg2+ with ROS membranes that are depleted of protein kinase activity. The reassociated protein kinase is insensitive to exogenous cyclic nucleotides, and it catalyzes the phosphorylation of the membrane protein, bleached rhodopsin. While the soluble and membrane-associated protein kinases may be interchangeable, they appear to be modulated by different biological signals; soluble protein kinase activity is increased by cyclic nucleotides whereas membrane-bound activity is enhanced when rhodopsin is bleached by light."}
{"id": "PMID:217413", "title": "Spin-label techniques for monitoring macromolecular rotational motion: empirical calibration under nonideal conditions.", "content": "Practical techniques are demonstrated for determining rotational correlation times of macromolecules from the first harmonic absorption electron spin reasonance spectra of tightly bound spin labels. The techniques are developed to compensate for such nonideal conditions as residual label motion, temperature dependence of rigid limit spectral parameters, and the presence of inhomogeneous line broadening. These effects are all shown to be of importance in monitoring the rotational motion of carbonmonoxyhemoglobin which is spin labeled with the tightly bound nitroxide label, 4-maleimido-2,2,6,6-tetramethylpiperidinyl-1-oxy. Spin-label interactions with other paramagnetic agents are also shown to produce spectral changes which are qualitatively similar to, but quantitatively different from, those resulting from increases in the rate of rotational motion.", "contents": "Spin-label techniques for monitoring macromolecular rotational motion: empirical calibration under nonideal conditions. Practical techniques are demonstrated for determining rotational correlation times of macromolecules from the first harmonic absorption electron spin reasonance spectra of tightly bound spin labels. The techniques are developed to compensate for such nonideal conditions as residual label motion, temperature dependence of rigid limit spectral parameters, and the presence of inhomogeneous line broadening. These effects are all shown to be of importance in monitoring the rotational motion of carbonmonoxyhemoglobin which is spin labeled with the tightly bound nitroxide label, 4-maleimido-2,2,6,6-tetramethylpiperidinyl-1-oxy. Spin-label interactions with other paramagnetic agents are also shown to produce spectral changes which are qualitatively similar to, but quantitatively different from, those resulting from increases in the rate of rotational motion."}
{"id": "PMID:217414", "title": "Lifetimes and NADH quenching of tryptophan fluorescence in pig heart lactate dehydrogenase.", "content": "The decay of tryptophan emission from pig heart lactate dehydrogenase following pulsed excitation has been recorded in Tris buffer solution at pH 7.4. All tryptophan residues emit. A good least-squares two-component fit is obtained with I(t)-0.53e-t/1.2 + 0.47e-t/68. A longer lived emitter (r=7.4--8.1 ns) is also observed. Bound NADH strongly quenches most of the 6.8-ns emission, but the 1.2-ns component is relatively unaffected. The fluorescence is moderately quenched by acrylamide and only slighty quenched by I- and Cs+. The pulsed and steady-state fluorescence is discussed in terms of a model with three lifetime classes of tryptophan, viz., 1, 4, and 8 ns. The three-dimensional structure of the enzyme--NADH complex is used to develop a description of the individual residues in terms of their lifetimes and sensitivity to NADH and I- quenching. The nonlinear NADH quenching is due to intersubunit energy transfer from Trp-248 to NADH.", "contents": "Lifetimes and NADH quenching of tryptophan fluorescence in pig heart lactate dehydrogenase. The decay of tryptophan emission from pig heart lactate dehydrogenase following pulsed excitation has been recorded in Tris buffer solution at pH 7.4. All tryptophan residues emit. A good least-squares two-component fit is obtained with I(t)-0.53e-t/1.2 + 0.47e-t/68. A longer lived emitter (r=7.4--8.1 ns) is also observed. Bound NADH strongly quenches most of the 6.8-ns emission, but the 1.2-ns component is relatively unaffected. The fluorescence is moderately quenched by acrylamide and only slighty quenched by I- and Cs+. The pulsed and steady-state fluorescence is discussed in terms of a model with three lifetime classes of tryptophan, viz., 1, 4, and 8 ns. The three-dimensional structure of the enzyme--NADH complex is used to develop a description of the individual residues in terms of their lifetimes and sensitivity to NADH and I- quenching. The nonlinear NADH quenching is due to intersubunit energy transfer from Trp-248 to NADH."}
{"id": "PMID:217416", "title": "Complete exchange of viral cholesterol.", "content": "The exchange of the cholesterol in the membranes of two enveloped viruses, Sindbis virus and vesicular stomatitis virus, with cholesterol present in lipid vesicles and in serum was measured. Biosynthetically labeled viral cholesterol underwent spontaneous and complete transfer to both lipid vesicles and to serum. The rate with which and the extent to which this process occurred were very similar for these two viruses. During incubation with lipid vesicles in excess, half of the viral cholesterol underwent transfer in approximately 4 h and more than 90% underwent transfer in 24h at 37 degrees C. Similar rates and extents of movement of viral cholesterol were observed when incubations were carried out with vesicles which contained cholesterol and phospholipid in the same molar ratio as in the virus or with egg lecithin vesicles which contained no cholesterol. When labeled cholesterol was present initially in the lipid vesicles, movement of cholesterol from the vesicles to the virus was observed. One implication of the fact that viral cholesterol undergoes extensive exchange with serum cholesterol is that cellular cholesterol is in equilibrium with that in the extracellular fluid.", "contents": "Complete exchange of viral cholesterol. The exchange of the cholesterol in the membranes of two enveloped viruses, Sindbis virus and vesicular stomatitis virus, with cholesterol present in lipid vesicles and in serum was measured. Biosynthetically labeled viral cholesterol underwent spontaneous and complete transfer to both lipid vesicles and to serum. The rate with which and the extent to which this process occurred were very similar for these two viruses. During incubation with lipid vesicles in excess, half of the viral cholesterol underwent transfer in approximately 4 h and more than 90% underwent transfer in 24h at 37 degrees C. Similar rates and extents of movement of viral cholesterol were observed when incubations were carried out with vesicles which contained cholesterol and phospholipid in the same molar ratio as in the virus or with egg lecithin vesicles which contained no cholesterol. When labeled cholesterol was present initially in the lipid vesicles, movement of cholesterol from the vesicles to the virus was observed. One implication of the fact that viral cholesterol undergoes extensive exchange with serum cholesterol is that cellular cholesterol is in equilibrium with that in the extracellular fluid."}
{"id": "PMID:217419", "title": "Diastereomers of 5'-O-adenosyl 3'-O-uridyl phosphorothioate: chemical synthesis and enzymatic properties.", "content": "A procedure is described for the synthesis of the title compounds via phosphotriester intermediates. The 2-cyanoethyl group is used to protect the P-SH function during the course of the synthesis. Resolution of the phosphorus diastereomers is accomplished at the phosphotriester stage. Removal of the 2-cyanoethyl group without racemization, followed by removal of the other protective groups, affords the optically pure diastereomers of 5'-O-adenosyl 3'-O-uridyl phosphorothioate. Their designation as Rp and Sp follows from the stereospecificity in the hydrolysis catalyzed by RNase A. These diastereomers are useful for the investigation of the stereospecificity as well as of the stereochemical course of action of nucleases. Snake venom exonuclease hydrolyses only the Rp diastereomer, whereas both diastereomers are substrates for RNases A and T2. The results with the latter indicate that RNase T2 also operates by an in-line mechanism.", "contents": "Diastereomers of 5'-O-adenosyl 3'-O-uridyl phosphorothioate: chemical synthesis and enzymatic properties. A procedure is described for the synthesis of the title compounds via phosphotriester intermediates. The 2-cyanoethyl group is used to protect the P-SH function during the course of the synthesis. Resolution of the phosphorus diastereomers is accomplished at the phosphotriester stage. Removal of the 2-cyanoethyl group without racemization, followed by removal of the other protective groups, affords the optically pure diastereomers of 5'-O-adenosyl 3'-O-uridyl phosphorothioate. Their designation as Rp and Sp follows from the stereospecificity in the hydrolysis catalyzed by RNase A. These diastereomers are useful for the investigation of the stereospecificity as well as of the stereochemical course of action of nucleases. Snake venom exonuclease hydrolyses only the Rp diastereomer, whereas both diastereomers are substrates for RNases A and T2. The results with the latter indicate that RNase T2 also operates by an in-line mechanism."}
{"id": "PMID:217421", "title": "Isolation and characterization of baby hamster kidney (BHK-21) cell modulator protein.", "content": "A Ca2+-dependent modulator protein has been isolated from BHK-21 cells. The purification requires heat treatment, ion-exchange chromatography, and gel filtration. The protein appears homogenous on sodium dodecyl sulfate--polyacrylamide and isoelectric focusing gels. The protein comigrates with purified smooth muscle and brain modulators. BHK-21 modulator is characterized by a high content of aspartic and glutamic acids and by a high phenylalanine/tyrosine ratio. It lacks both cysteine and tryptophan. The protein is effective in activating brain-modulator-deficient phosphodiesterase. It can also be used in assay systems to generate Ca2+-sensitive actin activation of both BHK-21 and smooth muscle myosins. Therefore, it is proposed that the BHK-21 modulator protein is a component of the Ca2+-dependent  mechanism involved in the regulation of actin--myosin interactions in BHK-21 cells.", "contents": "Isolation and characterization of baby hamster kidney (BHK-21) cell modulator protein. A Ca2+-dependent modulator protein has been isolated from BHK-21 cells. The purification requires heat treatment, ion-exchange chromatography, and gel filtration. The protein appears homogenous on sodium dodecyl sulfate--polyacrylamide and isoelectric focusing gels. The protein comigrates with purified smooth muscle and brain modulators. BHK-21 modulator is characterized by a high content of aspartic and glutamic acids and by a high phenylalanine/tyrosine ratio. It lacks both cysteine and tryptophan. The protein is effective in activating brain-modulator-deficient phosphodiesterase. It can also be used in assay systems to generate Ca2+-sensitive actin activation of both BHK-21 and smooth muscle myosins. Therefore, it is proposed that the BHK-21 modulator protein is a component of the Ca2+-dependent  mechanism involved in the regulation of actin--myosin interactions in BHK-21 cells."}
{"id": "PMID:217424", "title": "H3.H4 tetramer directs DNA and core histone octamer assembly in the nucleosome core particle.", "content": "The way in which histones interact with DNA during in vitro assembly of nucleohistone has been examined. Chicken erythrocyte core histones H2A, H2B, H3, and H4 and lambdaDNA in 2 M NaCl were allowed to interact by stepwise decrease in the salt concentration. Binding, although weak, was first observed at 1.4 M NaCl and was essentially completed at 0.6 M NaCl. Analysis of the DNA-bound histones revealed that each of the histones in the pairs H2A,H2B and H3,H4 was always present in equimolar amounts and that the relative proportion of each pair was constant between 1.4 and 0.8 M NaCl. Evidence is presented suggesting that binding occurred via complexes of the four histones, the nature of which is likely to reflect the equilibrium among the octamer and its products of dissociation (Ruiz-Carrillo, A., & Jorcano, J.L. (1979) Biochemistry (preceding paper in this issue)). The presence of complexes of the four core histones is, however not required for the correct assembly of the nucleosome core particle. Nucleohistones obtained by adding at progressively lower ionic strengths the dimer H2A.H2B to the H3.H4-DNA complex (split reconstitutions) had the same characteristics as those assembled with the core histone complexes.", "contents": "H3.H4 tetramer directs DNA and core histone octamer assembly in the nucleosome core particle. The way in which histones interact with DNA during in vitro assembly of nucleohistone has been examined. Chicken erythrocyte core histones H2A, H2B, H3, and H4 and lambdaDNA in 2 M NaCl were allowed to interact by stepwise decrease in the salt concentration. Binding, although weak, was first observed at 1.4 M NaCl and was essentially completed at 0.6 M NaCl. Analysis of the DNA-bound histones revealed that each of the histones in the pairs H2A,H2B and H3,H4 was always present in equimolar amounts and that the relative proportion of each pair was constant between 1.4 and 0.8 M NaCl. Evidence is presented suggesting that binding occurred via complexes of the four histones, the nature of which is likely to reflect the equilibrium among the octamer and its products of dissociation (Ruiz-Carrillo, A., & Jorcano, J.L. (1979) Biochemistry (preceding paper in this issue)). The presence of complexes of the four core histones is, however not required for the correct assembly of the nucleosome core particle. Nucleohistones obtained by adding at progressively lower ionic strengths the dimer H2A.H2B to the H3.H4-DNA complex (split reconstitutions) had the same characteristics as those assembled with the core histone complexes."}
{"id": "PMID:217425", "title": "Molecular weight of (Na+,K+)ATPase from shark rectal gland.", "content": "The (Na+,k+)ATPase from the rectal gland of Carcharhinus obscurus has been solubilized in Lubrol WX as an active complex containing 379,900 g of protein and 61 mol of phospholipid. This detergent-lipid-protein complex contains two catalytic subunits of molecular weight 106,400 and four glycopeptide subunits of protein molecular weight 36,600. The latter subunit has a total molecular weight of 51,700 when the carbohydrate is included. Attempts to dissociate this active enzyme complex to smaller size by increasing the detergent concentration led to inactivation. Thus, the smallest active particle in the presence of Lubrol WX contains the two polypeptide subunits in a mole ratio of 2:4 under conditions where the micellar form of detergent is present at a 70:1 molar ratio. This large excess of Lubrol WX eliminates any possibility of artificial togetherness as the result of statistical considerations.", "contents": "Molecular weight of (Na+,K+)ATPase from shark rectal gland. The (Na+,k+)ATPase from the rectal gland of Carcharhinus obscurus has been solubilized in Lubrol WX as an active complex containing 379,900 g of protein and 61 mol of phospholipid. This detergent-lipid-protein complex contains two catalytic subunits of molecular weight 106,400 and four glycopeptide subunits of protein molecular weight 36,600. The latter subunit has a total molecular weight of 51,700 when the carbohydrate is included. Attempts to dissociate this active enzyme complex to smaller size by increasing the detergent concentration led to inactivation. Thus, the smallest active particle in the presence of Lubrol WX contains the two polypeptide subunits in a mole ratio of 2:4 under conditions where the micellar form of detergent is present at a 70:1 molar ratio. This large excess of Lubrol WX eliminates any possibility of artificial togetherness as the result of statistical considerations."}
{"id": "PMID:217427", "title": "Cyclic adenosine monophosphate dependent and independent phosphorylation of sarcolemma membrane proteins in perfused rat heart.", "content": "This study was initiated in order to elaborate further on the mechanism by which epinephrine modulates cardiac function via protein phosphorylation. A membrane fraction has been isolated from freeze-clamped perfused rat heart that contains two phosphoproteins. These proteins have molecular weights of 36,000 (A protein) and 27,000 (B protein). The phosphorylation of the A protein occurs during the equilibration of the heart with inorganic [32P]phosphate. The phosphorylation of the B protein occurs in response to epinephrine. The A and B proteins are apparently identical with two phosphoproteins in enriched preparations of sarcolemma. The protein of the sarcolemma preparation equivalent to the A protein is phosphorylated in vitro by both cAMP-independent and cAMP-dependent protein kinases. The phosphorylation of the protein of the sarcolemma preparation equivalent to the B protein is catalyzed by the cAMP-dependent protein kinase. Thus the patterns of phosphorylation of these proteins in vivo and in vitro are compatible. The phosphorylation of the B protein has been documented in vitro to modulate calcium transport (Will, H., et al. (1973) Acta Biol. Med. Ger. 31, 45-52), but the response to epinephrine in the perfused heart is not apparently coordinated with the catecholamine-induced inotropic effect.", "contents": "Cyclic adenosine monophosphate dependent and independent phosphorylation of sarcolemma membrane proteins in perfused rat heart. This study was initiated in order to elaborate further on the mechanism by which epinephrine modulates cardiac function via protein phosphorylation. A membrane fraction has been isolated from freeze-clamped perfused rat heart that contains two phosphoproteins. These proteins have molecular weights of 36,000 (A protein) and 27,000 (B protein). The phosphorylation of the A protein occurs during the equilibration of the heart with inorganic [32P]phosphate. The phosphorylation of the B protein occurs in response to epinephrine. The A and B proteins are apparently identical with two phosphoproteins in enriched preparations of sarcolemma. The protein of the sarcolemma preparation equivalent to the A protein is phosphorylated in vitro by both cAMP-independent and cAMP-dependent protein kinases. The phosphorylation of the protein of the sarcolemma preparation equivalent to the B protein is catalyzed by the cAMP-dependent protein kinase. Thus the patterns of phosphorylation of these proteins in vivo and in vitro are compatible. The phosphorylation of the B protein has been documented in vitro to modulate calcium transport (Will, H., et al. (1973) Acta Biol. Med. Ger. 31, 45-52), but the response to epinephrine in the perfused heart is not apparently coordinated with the catecholamine-induced inotropic effect."}
{"id": "PMID:217428", "title": "Azethoxyl nitroxide spin labels. ESR studies involving thiourea crystals, model membrane systems and chromatophores, and chemical reduction with ascorbate and dithiothreitol.", "content": "Trans- and cis-azethoxyl nitroxides 1, 2, 3 and 4 can be trapped in the cavities of thiourea crystals. The presence of a single gauche conformation on either side of the pyrrolidine ring within the crystals was indicated by the ESR spectra. Rotation about the long molecular axis then corresponds approximately to y-axis motion of the nitroxide moiety. Proxyl nitroxides in which the nitroxide group is located on the penultimate carbon of long chain lipids can also be trapped and were shown to adopt the azethoxyl conformation in the thiourea crystals. The measured deltaA values (A parallel to - A perpendicular) of oriented egg lecithin multilayers containing trans- and cis-azethoxyl nitroxides 1 and 2 were quite small, consistent with the unique orientation of the nitroxide principal axes with respect to the long axis of the molecule. The deltaA values for a series of lipids bearing a label near the terminus of the chain were very similar to that of 1, showing that the azethoxyl conformation is likely the predominant one in these labels in orienting systems. Computer simulations of the ESR spectra of 1 and 2 in egg lecithin vesicles provided values for molecular orientation and motion parameters consistent with those expected from a consideration of molecular models in the extended (all trans) conformation. Azethoxyl nitroxides have also proven useful in the investigation of motion restricted (boundary) lipid in a lipid-protein system. Thus, the values (69 +/- 10%) for the amount of boundary lipid in the chromatophore membranes from Rhodopseudomonas sphaeroides as determined using trans- 2 and cis- 2 are in good agreement with values using 16-doxylstearic acid (64 +/- 3%). The fact that all three labels show about the same fraction of boundary lipid in this system indicates that the lipid binding sites are relatively insensitive to the geometry of the lipid chain. Also, both 1 and 2 appear to be able to detect a third lipid environment not seen with the doxyl fatty acid. The apparent fluidity of this component lies between that of boundary and bilayer lipid. The unique orientation of the nitroxide principal axes with respect to the long molecular axis in azethoxyl nitroxides 1 and 2 allows detection of hindrance to rotation about the long molecular axis, in contrast to the analogous doxyl and proxyl fatty acids. Comparative reduction studies using ascorbate and dithiothreitol indicate that azethoxyl nitroxides are slightly more resistant toward reduction than proxyl nitroxides and much more resistant than doxyl nitroxides.", "contents": "Azethoxyl nitroxide spin labels. ESR studies involving thiourea crystals, model membrane systems and chromatophores, and chemical reduction with ascorbate and dithiothreitol. Trans- and cis-azethoxyl nitroxides 1, 2, 3 and 4 can be trapped in the cavities of thiourea crystals. The presence of a single gauche conformation on either side of the pyrrolidine ring within the crystals was indicated by the ESR spectra. Rotation about the long molecular axis then corresponds approximately to y-axis motion of the nitroxide moiety. Proxyl nitroxides in which the nitroxide group is located on the penultimate carbon of long chain lipids can also be trapped and were shown to adopt the azethoxyl conformation in the thiourea crystals. The measured deltaA values (A parallel to - A perpendicular) of oriented egg lecithin multilayers containing trans- and cis-azethoxyl nitroxides 1 and 2 were quite small, consistent with the unique orientation of the nitroxide principal axes with respect to the long axis of the molecule. The deltaA values for a series of lipids bearing a label near the terminus of the chain were very similar to that of 1, showing that the azethoxyl conformation is likely the predominant one in these labels in orienting systems. Computer simulations of the ESR spectra of 1 and 2 in egg lecithin vesicles provided values for molecular orientation and motion parameters consistent with those expected from a consideration of molecular models in the extended (all trans) conformation. Azethoxyl nitroxides have also proven useful in the investigation of motion restricted (boundary) lipid in a lipid-protein system. Thus, the values (69 +/- 10%) for the amount of boundary lipid in the chromatophore membranes from Rhodopseudomonas sphaeroides as determined using trans- 2 and cis- 2 are in good agreement with values using 16-doxylstearic acid (64 +/- 3%). The fact that all three labels show about the same fraction of boundary lipid in this system indicates that the lipid binding sites are relatively insensitive to the geometry of the lipid chain. Also, both 1 and 2 appear to be able to detect a third lipid environment not seen with the doxyl fatty acid. The apparent fluidity of this component lies between that of boundary and bilayer lipid. The unique orientation of the nitroxide principal axes with respect to the long molecular axis in azethoxyl nitroxides 1 and 2 allows detection of hindrance to rotation about the long molecular axis, in contrast to the analogous doxyl and proxyl fatty acids. Comparative reduction studies using ascorbate and dithiothreitol indicate that azethoxyl nitroxides are slightly more resistant toward reduction than proxyl nitroxides and much more resistant than doxyl nitroxides."}
{"id": "PMID:217429", "title": "Interaction of plasma lipoproteins with erythrocytes. I. Alteration of erythrocyte morphology.", "content": "Intact erythrocytes incubated in the presence of low density lipoproteins (LDL) undergo a time-dependent morphologic transformation from biconcave discs to spherocytes within 4 h. No shape change is observed when erythrocytes are incubated with high density lipoproteins (HDL). The LDL-induced change in erythrocyte morphology occurs without concomitant leakage of hemoglobin from the cell or depletion of intracellular ATP; no change in the distribution of the major lipids of the erythrocyte membranes was detected. The alteration of morphology does require attachment of LDL to the erythrocyte surface. The LDL-induced morphologic alteration is inhibited by HDL, but not by serum albumin. HDL prevent the attachment of LDL to the cell membrane; however, the HDL subfractions, HDL2 and HDL3, are only partially effective. These data suggest that normal erythrocyte morphology and cell function may depend on the concentration and composition of the circulating lipoproteins.", "contents": "Interaction of plasma lipoproteins with erythrocytes. I. Alteration of erythrocyte morphology. Intact erythrocytes incubated in the presence of low density lipoproteins (LDL) undergo a time-dependent morphologic transformation from biconcave discs to spherocytes within 4 h. No shape change is observed when erythrocytes are incubated with high density lipoproteins (HDL). The LDL-induced change in erythrocyte morphology occurs without concomitant leakage of hemoglobin from the cell or depletion of intracellular ATP; no change in the distribution of the major lipids of the erythrocyte membranes was detected. The alteration of morphology does require attachment of LDL to the erythrocyte surface. The LDL-induced morphologic alteration is inhibited by HDL, but not by serum albumin. HDL prevent the attachment of LDL to the cell membrane; however, the HDL subfractions, HDL2 and HDL3, are only partially effective. These data suggest that normal erythrocyte morphology and cell function may depend on the concentration and composition of the circulating lipoproteins."}
{"id": "PMID:217430", "title": "Interaction of plasma lipoproteins with erythrocytes. II. Modulation of membrane-associated enzymes.", "content": "When incubated with intact erythrocytes, low density lipoproteins (LDL) decrease the phosphate content of erythrocyte spectrin allowing the cells to undergo morphological transformation. The phosphate content of spectrin depends on the balance between the activity of membrane-associated cyclic AMP-independent protein kinases and phosphoprotein phosphates. LDL do not influence the activity of membrane-associated cyclic AMP-independent protein kinases; these lipoproteins activate by 2-fold and greater membrane-associated phosphatases as determined by hydrolysis of p-nitrophenyl phosphate and by phosphate hydrolysis of phosphorylated erythrocyte membrane proteins. We conclude that LDL interact at the exterior surface of the erythrocyte to stimulate dephosphorylation of spectrin. The significance of this conclusion is augmented by the fact that spectrin, the target for LDL-induced dephosphorylation, specifies cell morphology and modulates the distribution of cell-surface receptors. LDL also render erythrocyte acetylcholinesterase less susceptible to inhition by F-. Lipoproteins in the high density class (HDL) do not stimulate dephosphorylation of spectrin, and they are consequently unable to alter erythrocyte morphology. HDL do prevent the LDL-induced activation of membrane phosphatase. The inhibitory capacity of HDL is observed over the range of LDL:HDL (w/w) which exists in the plasma of normolipemic humans.", "contents": "Interaction of plasma lipoproteins with erythrocytes. II. Modulation of membrane-associated enzymes. When incubated with intact erythrocytes, low density lipoproteins (LDL) decrease the phosphate content of erythrocyte spectrin allowing the cells to undergo morphological transformation. The phosphate content of spectrin depends on the balance between the activity of membrane-associated cyclic AMP-independent protein kinases and phosphoprotein phosphates. LDL do not influence the activity of membrane-associated cyclic AMP-independent protein kinases; these lipoproteins activate by 2-fold and greater membrane-associated phosphatases as determined by hydrolysis of p-nitrophenyl phosphate and by phosphate hydrolysis of phosphorylated erythrocyte membrane proteins. We conclude that LDL interact at the exterior surface of the erythrocyte to stimulate dephosphorylation of spectrin. The significance of this conclusion is augmented by the fact that spectrin, the target for LDL-induced dephosphorylation, specifies cell morphology and modulates the distribution of cell-surface receptors. LDL also render erythrocyte acetylcholinesterase less susceptible to inhition by F-. Lipoproteins in the high density class (HDL) do not stimulate dephosphorylation of spectrin, and they are consequently unable to alter erythrocyte morphology. HDL do prevent the LDL-induced activation of membrane phosphatase. The inhibitory capacity of HDL is observed over the range of LDL:HDL (w/w) which exists in the plasma of normolipemic humans."}
{"id": "PMID:217431", "title": "Mathematical modelling of ATP, K+ and Na+ interactions with (Na+ + K+)-ATPase occurring under equilibrium conditions.", "content": "The controlling effect of ATP, K+ and Na+ on the rate of (Na+ + K+)-ATPase inactivation by 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-C1) is used for the mathematical modelling of the interaction of the effectors with the enzyme under equilibrium conditions. 1. Of a series of conceivable interaction models, designed without conceptual restrictions to describe the effector control of inactivation kinetics, only one fits the experimental data described in a preceding paper. 2. The model is characterized by the coexistence of two binding sites for ATP and the coexistence of two separate binding sites for K+ and Na+ on the enzyme-ATP complex. On the basis of this model, the effector parameters fitting the experimental data most closely are estimated by means of nonlinear least-squares fits. 3. The apparent dissociation constants for ATP fo the enzyme-ATP complex or of the enzyme-(ATP)2 complex are computed to lie near 0.0024 mM and 0.34 mM, respectively, irrespective of whether K+ and Na+ were absent or K+ and K+ plus Na+, respectively, were present in the experiments. 4. The origin of the high and the low affinity site for binding of ATP to the (Na+ + K+)-ATPase molecule is traced back to the coexistence of two catalytic centres which, although primarily equivalent as to the reactivity of their thiol groups with NBD-C1, are induced into anticooperative communication by ATP binding and thus show an induced geometric asymmetry. 5. On the basis of the interaction model outlined under item 2 the apparent dissociation constant for K+ or Na+ in the (K+ + Na+)-liganded enzyme-ATP complex are computed to be 1.7 mM and 3.5 mM, respectively. 6. The conclusions concerning the coexistence of two primarily equivalent but anticooperatively interacting catalytic centres and the coexistence of two separate ionophoric centres for Na+ and K+ correspond to the appropriate basic postulates of the flip-flop concept of (Na+ + K+)-ATPase mechanism.", "contents": "Mathematical modelling of ATP, K+ and Na+ interactions with (Na+ + K+)-ATPase occurring under equilibrium conditions. The controlling effect of ATP, K+ and Na+ on the rate of (Na+ + K+)-ATPase inactivation by 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-C1) is used for the mathematical modelling of the interaction of the effectors with the enzyme under equilibrium conditions. 1. Of a series of conceivable interaction models, designed without conceptual restrictions to describe the effector control of inactivation kinetics, only one fits the experimental data described in a preceding paper. 2. The model is characterized by the coexistence of two binding sites for ATP and the coexistence of two separate binding sites for K+ and Na+ on the enzyme-ATP complex. On the basis of this model, the effector parameters fitting the experimental data most closely are estimated by means of nonlinear least-squares fits. 3. The apparent dissociation constants for ATP fo the enzyme-ATP complex or of the enzyme-(ATP)2 complex are computed to lie near 0.0024 mM and 0.34 mM, respectively, irrespective of whether K+ and Na+ were absent or K+ and K+ plus Na+, respectively, were present in the experiments. 4. The origin of the high and the low affinity site for binding of ATP to the (Na+ + K+)-ATPase molecule is traced back to the coexistence of two catalytic centres which, although primarily equivalent as to the reactivity of their thiol groups with NBD-C1, are induced into anticooperative communication by ATP binding and thus show an induced geometric asymmetry. 5. On the basis of the interaction model outlined under item 2 the apparent dissociation constant for K+ or Na+ in the (K+ + Na+)-liganded enzyme-ATP complex are computed to be 1.7 mM and 3.5 mM, respectively. 6. The conclusions concerning the coexistence of two primarily equivalent but anticooperatively interacting catalytic centres and the coexistence of two separate ionophoric centres for Na+ and K+ correspond to the appropriate basic postulates of the flip-flop concept of (Na+ + K+)-ATPase mechanism."}
{"id": "PMID:217432", "title": "Viral and non-viral induced fusion of pronase-digested human erythrocyte ghosts.", "content": "Human erythrocyte ghosts but was able to fuse only iso-human erythrocyte ghosts. Iso- and hypo-human erythrocyte ghosts were incubated with the proteolytic enzyme pronase under isotonic (iso-human erythrocyte ghosts) or hypotonic (hypo-human erythrocyte ghosts) conditions. Gel electrophoresis and electron microscope (freeze-etching) studies revealed that most of the erythrocyte membrane polypeptides were hydrolyzed by pronase under hypotonic conditions. Sendai virus readily agglutinated both pronase-digested iso-human erythrocyte ghosts and hypo-human erythrocyte ghosts were fused by the non-viral fusogenic agent glyceromonooleate. Freeze-etching studies revealed that during fusion the membranes of pronase-digested human erythrocyte ghosts are intermixed.", "contents": "Viral and non-viral induced fusion of pronase-digested human erythrocyte ghosts. Human erythrocyte ghosts but was able to fuse only iso-human erythrocyte ghosts. Iso- and hypo-human erythrocyte ghosts were incubated with the proteolytic enzyme pronase under isotonic (iso-human erythrocyte ghosts) or hypotonic (hypo-human erythrocyte ghosts) conditions. Gel electrophoresis and electron microscope (freeze-etching) studies revealed that most of the erythrocyte membrane polypeptides were hydrolyzed by pronase under hypotonic conditions. Sendai virus readily agglutinated both pronase-digested iso-human erythrocyte ghosts and hypo-human erythrocyte ghosts were fused by the non-viral fusogenic agent glyceromonooleate. Freeze-etching studies revealed that during fusion the membranes of pronase-digested human erythrocyte ghosts are intermixed."}
{"id": "PMID:217433", "title": "The effect of cyclic nucleotides and protein phosphorylation on calcium permeability and binding in the sarcoplasmic reticulum.", "content": "In the absence of cyclic nucleotides heart microsomes have two classes of calcium binding sites with binding constants of 0.69 and 0.071 micron-1 and capacities of 2.2 and 9.7 nmol/mg protein, respectively. Neither cyclic AMP nor monobutyryl cyclic AMP affect binding but cyclic GMP and monobutyryl cyclic GMP cause the complete loss of the high affinity calcium binding sites, Cyclic GMP (but not monobutyryl cyclic GMP) also causes a decrease in the binding constant of the low affinity binding sites. AMP, GMP and Tris-butyrate do not affect calcium binding. The effects of the cyclic nucleotides are direct and are not mediated by protein phosphorylation. Phosphorylation of microsomal proteins increases the binding constant but not the capacity of the high affinity calcium binding sites. The capacity and also, perhaps, binding constant of the low affinity sites is also increased by phosphorylation. In additon to their effects on calcium binding the cyclic nucleotides also affect the movements of calcium into and out of the microsomes. The effects are again direct and not mediated by protein phosphorylation. Cyclic GMP decreases the rate of Ca2+ efflux from preloaded cardiac microsomes and also appears to decrease the rate of uptake of Ca2+ by cardiac microsomes though this effect is less clear cut than the action on efflux. The cyclic nucleotide has a half maximal effect at a concentration of 100 microns. By contrast cyclic AMP increases the rate of influx of Ca2+ into heart microsomes and the rate of efflux of Ca2+ from preloaded preparations. The effect is, however, rather slight. It is suggested that the most obvious interpretation of these results is that cyclic GMP decreases the Ca2+ permeability of the cardiac microsomal membrane while cyclic AMP increases the permeability. In contrast to the results found with membrane preparations from certain other tissues phosphorylation of cardiac microsomal proteins does not appear to alter Ca2+ efflux or influx out of, or into, cardiac microsomal preparations. It is thus concluded that phosphorylation of cardiac microsomal proteins does not affect the Ca2+ permeability of the microsomal membrane.", "contents": "The effect of cyclic nucleotides and protein phosphorylation on calcium permeability and binding in the sarcoplasmic reticulum. In the absence of cyclic nucleotides heart microsomes have two classes of calcium binding sites with binding constants of 0.69 and 0.071 micron-1 and capacities of 2.2 and 9.7 nmol/mg protein, respectively. Neither cyclic AMP nor monobutyryl cyclic AMP affect binding but cyclic GMP and monobutyryl cyclic GMP cause the complete loss of the high affinity calcium binding sites, Cyclic GMP (but not monobutyryl cyclic GMP) also causes a decrease in the binding constant of the low affinity binding sites. AMP, GMP and Tris-butyrate do not affect calcium binding. The effects of the cyclic nucleotides are direct and are not mediated by protein phosphorylation. Phosphorylation of microsomal proteins increases the binding constant but not the capacity of the high affinity calcium binding sites. The capacity and also, perhaps, binding constant of the low affinity sites is also increased by phosphorylation. In additon to their effects on calcium binding the cyclic nucleotides also affect the movements of calcium into and out of the microsomes. The effects are again direct and not mediated by protein phosphorylation. Cyclic GMP decreases the rate of Ca2+ efflux from preloaded cardiac microsomes and also appears to decrease the rate of uptake of Ca2+ by cardiac microsomes though this effect is less clear cut than the action on efflux. The cyclic nucleotide has a half maximal effect at a concentration of 100 microns. By contrast cyclic AMP increases the rate of influx of Ca2+ into heart microsomes and the rate of efflux of Ca2+ from preloaded preparations. The effect is, however, rather slight. It is suggested that the most obvious interpretation of these results is that cyclic GMP decreases the Ca2+ permeability of the cardiac microsomal membrane while cyclic AMP increases the permeability. In contrast to the results found with membrane preparations from certain other tissues phosphorylation of cardiac microsomal proteins does not appear to alter Ca2+ efflux or influx out of, or into, cardiac microsomal preparations. It is thus concluded that phosphorylation of cardiac microsomal proteins does not affect the Ca2+ permeability of the microsomal membrane."}
{"id": "PMID:217434", "title": "Electron spin resonance, hematological, and deformability studies of erythrocytes from patients with Huntington's disease.", "content": "Electron spin resonance, hematologic, and deformability studies of erythrocytes from patients with Huntington's disease have been performed A decreased deformability of Huntington's disease erythrocytes compared to normal controls was demonstrated. No difference in erythrocyte hematologic indices, osmotic fragility, reticulocyte counts, or intracellular Na+ concentration was found. Huntington's disease serum had no demonstrable effect on electron spin resonance parameters of a protein-specific spin label attached to membrane proteins in control erythrocytes compared to the effect of control serum. This finding suggests that under the conditions employed no serum component or circulating factor is responsible for the changes in the physical state of membrane proteins in Huntington's disease erythrocytes (Butterfield, D.A., Oeswein, J.Q. and Markesbery, W.R. (1977) Nature 267, 453--455). No alteration in lipid fluidity of Huntington's disease erythrocyte membranes could be discerned suggesting that the underlying molecular defect in Huntington's disease involves a membrane protein. The results of the present studies on erythrocytes strongly support the concept that Huntington's disease is associated with a generalized membrane abnormality.", "contents": "Electron spin resonance, hematological, and deformability studies of erythrocytes from patients with Huntington's disease. Electron spin resonance, hematologic, and deformability studies of erythrocytes from patients with Huntington's disease have been performed A decreased deformability of Huntington's disease erythrocytes compared to normal controls was demonstrated. No difference in erythrocyte hematologic indices, osmotic fragility, reticulocyte counts, or intracellular Na+ concentration was found. Huntington's disease serum had no demonstrable effect on electron spin resonance parameters of a protein-specific spin label attached to membrane proteins in control erythrocytes compared to the effect of control serum. This finding suggests that under the conditions employed no serum component or circulating factor is responsible for the changes in the physical state of membrane proteins in Huntington's disease erythrocytes (Butterfield, D.A., Oeswein, J.Q. and Markesbery, W.R. (1977) Nature 267, 453--455). No alteration in lipid fluidity of Huntington's disease erythrocyte membranes could be discerned suggesting that the underlying molecular defect in Huntington's disease involves a membrane protein. The results of the present studies on erythrocytes strongly support the concept that Huntington's disease is associated with a generalized membrane abnormality."}
{"id": "PMID:217435", "title": "The purification of Q-containing tRNAs by periodate modification. Purification and nucleoside composition of two related Drosophila tyrosine tRNAs.", "content": "A simple procedure for the purification of Drosophila tRNAs which contain the hypermodified nucleoside Q was developed. The cis-diol group of Q renders it susceptible to attack by sodium periodate, with the resultant formation of a hydrophobic pyrrol ring structure. The increase in hydrophobicity after periodate modification, of those tRNA species which contain the Q nucleoside, causes them to be selectively retarded on benzoylated DEAE-cellulose or RPC-5 columns, and allows their isolation in essentially pure form. Utilizing this property, the Q-containing tyrosine tRNA from Drosophila, tRNATyr1delta, was purified. The non-Q-containing tyrosine tRNA, tRNA, tRNATyr1gamma, was also purified, and the nucleoside compositions of the two were determined and compared. In addition to the Q nucleoside, these tRNAs appear to differ by the presence (tRNATyr1delta) or absence (tRNATyr1gamma) of 5-methylcytidine. In all other respects, these tRNAs appear to be identical, and are probably products of the same gene which differ in their levels of post-transcriptional modification.", "contents": "The purification of Q-containing tRNAs by periodate modification. Purification and nucleoside composition of two related Drosophila tyrosine tRNAs. A simple procedure for the purification of Drosophila tRNAs which contain the hypermodified nucleoside Q was developed. The cis-diol group of Q renders it susceptible to attack by sodium periodate, with the resultant formation of a hydrophobic pyrrol ring structure. The increase in hydrophobicity after periodate modification, of those tRNA species which contain the Q nucleoside, causes them to be selectively retarded on benzoylated DEAE-cellulose or RPC-5 columns, and allows their isolation in essentially pure form. Utilizing this property, the Q-containing tyrosine tRNA from Drosophila, tRNATyr1delta, was purified. The non-Q-containing tyrosine tRNA, tRNA, tRNATyr1gamma, was also purified, and the nucleoside compositions of the two were determined and compared. In addition to the Q nucleoside, these tRNAs appear to differ by the presence (tRNATyr1delta) or absence (tRNATyr1gamma) of 5-methylcytidine. In all other respects, these tRNAs appear to be identical, and are probably products of the same gene which differ in their levels of post-transcriptional modification."}
{"id": "PMID:217436", "title": "Thiaisoleucine and protein synthesis.", "content": "Thiaisoleucine is an isoleucine analogue having the gamma-methylene group of the valerianic carbon chain substituted by a sulphur atom. It has been demonstrated that thiaisoleucine is activated and transferred to tRNAIle by rat liver aminoacyl-tRNA synthetase and inhibits isoleucine incorporation into polypeptides in protein synthesizing systems from rat liver or rabbit reticulocytes, whereas it does not affect either leucine incorporation or ribosome run-off or polypeptide chain elongation rate. All tests were performed in comparison with O-methyl-threonine, an isoleucine analogue with the gamma-methylene group substituted by an oxygen atom. In all the reactions studied, both thiaisoleucine and O-methyl-threonine act as competitive inhibitors of isoleucine. With respect to O-methyl-threonine, thiaisoleucine shows higher activity as an isoleucine inhibitor.", "contents": "Thiaisoleucine and protein synthesis. Thiaisoleucine is an isoleucine analogue having the gamma-methylene group of the valerianic carbon chain substituted by a sulphur atom. It has been demonstrated that thiaisoleucine is activated and transferred to tRNAIle by rat liver aminoacyl-tRNA synthetase and inhibits isoleucine incorporation into polypeptides in protein synthesizing systems from rat liver or rabbit reticulocytes, whereas it does not affect either leucine incorporation or ribosome run-off or polypeptide chain elongation rate. All tests were performed in comparison with O-methyl-threonine, an isoleucine analogue with the gamma-methylene group substituted by an oxygen atom. In all the reactions studied, both thiaisoleucine and O-methyl-threonine act as competitive inhibitors of isoleucine. With respect to O-methyl-threonine, thiaisoleucine shows higher activity as an isoleucine inhibitor."}
{"id": "PMID:217437", "title": "Solubilization of membrane-bound adenylate cyclase of isolated rat adrenal cortex cells.", "content": "The membrane-bound adenylase cyclase (ATP pyrosphosphate-lyase (cyclizing), EC 4.6.1.1) of isolated rat adrenal cortex cells can be rendered soluble using 0.02 M Lubrol 12A9. The solubilized enzyme can be filtered through Milipore filters with pores 0.22 micron in diameter. Using gel filtration, on Sephadex G-200, adenylate cyclase activity was eluted with a distribution coefficient of 0.139, whereas on Sephadex G-100 the activity was eluted in the excluded volume. Half-maximum activation of the postulated guanyl nucleotide regulator site of adenylate was achieved with 5'-guanylyl-imidodiphosphate at a concentration of 1 . 10(-6)M. In contrast, however, using intact isolated rat adrenal cortex cells the guanyl nucleotide regulator site could not be stimulated by 5'-guanylyl-imidodiphosphate.", "contents": "Solubilization of membrane-bound adenylate cyclase of isolated rat adrenal cortex cells. The membrane-bound adenylase cyclase (ATP pyrosphosphate-lyase (cyclizing), EC 4.6.1.1) of isolated rat adrenal cortex cells can be rendered soluble using 0.02 M Lubrol 12A9. The solubilized enzyme can be filtered through Milipore filters with pores 0.22 micron in diameter. Using gel filtration, on Sephadex G-200, adenylate cyclase activity was eluted with a distribution coefficient of 0.139, whereas on Sephadex G-100 the activity was eluted in the excluded volume. Half-maximum activation of the postulated guanyl nucleotide regulator site of adenylate was achieved with 5'-guanylyl-imidodiphosphate at a concentration of 1 . 10(-6)M. In contrast, however, using intact isolated rat adrenal cortex cells the guanyl nucleotide regulator site could not be stimulated by 5'-guanylyl-imidodiphosphate."}
{"id": "PMID:217438", "title": "Conversion of dihydroorotate to orotate in parasitic protozoa.", "content": "The conversion of dihydroorotate to orotate, one of the key reactions in the de novo pyrimidine biosynthetic pathway, has been studied in a number of parasitic protozoa. Enzyme activities capable of carrying out this reaction were detected in six members of the Kinetoplastida (Trypanosoma brucei, Trypanosoma congolense, Trypanosoma vivax, Trypanosoma lewisi, Trypanosoma cruzi, Leishmania enriettii) and three members of the genus Plasmodium (P. knowlesi, P. berghei, P. gallinaceum). The mechanism of the reaction in the two groups of protozoa were quite distinct. In the Kinetoplastida, the enzyme is an hydroxylase which occurs in the soluble fraction of the cell and probably requires tetrahydrobiopterin for activity. In contrast, in Plasmodium, the enzyme is a dehydrogenase which is particulate, probably mitochondrial, and intimately connected to the electron transport chain to which it passes electrons directly, probably at the ubiquinone level. Neither activity is regulated by fully formed pyrimidines. The enzyme in Plasmodium is similar in mechanism to the isofunctional mammalian enzyme. However, since malarial ubiquinones are apparently different from those in the mammal and since menoctone, which is active in vivo in experimental malaria, is a good inhibitor of the malarial enzyme, it could represent a useful target for chemotherapeutic attack. The enzyme in the Kinetoplastida is quite distinct from that in the mammal so that it too apparently falls into this category, though none of the currently used antitrypanosomal drugs appears to block it activity at physiological concentrations.", "contents": "Conversion of dihydroorotate to orotate in parasitic protozoa. The conversion of dihydroorotate to orotate, one of the key reactions in the de novo pyrimidine biosynthetic pathway, has been studied in a number of parasitic protozoa. Enzyme activities capable of carrying out this reaction were detected in six members of the Kinetoplastida (Trypanosoma brucei, Trypanosoma congolense, Trypanosoma vivax, Trypanosoma lewisi, Trypanosoma cruzi, Leishmania enriettii) and three members of the genus Plasmodium (P. knowlesi, P. berghei, P. gallinaceum). The mechanism of the reaction in the two groups of protozoa were quite distinct. In the Kinetoplastida, the enzyme is an hydroxylase which occurs in the soluble fraction of the cell and probably requires tetrahydrobiopterin for activity. In contrast, in Plasmodium, the enzyme is a dehydrogenase which is particulate, probably mitochondrial, and intimately connected to the electron transport chain to which it passes electrons directly, probably at the ubiquinone level. Neither activity is regulated by fully formed pyrimidines. The enzyme in Plasmodium is similar in mechanism to the isofunctional mammalian enzyme. However, since malarial ubiquinones are apparently different from those in the mammal and since menoctone, which is active in vivo in experimental malaria, is a good inhibitor of the malarial enzyme, it could represent a useful target for chemotherapeutic attack. The enzyme in the Kinetoplastida is quite distinct from that in the mammal so that it too apparently falls into this category, though none of the currently used antitrypanosomal drugs appears to block it activity at physiological concentrations."}
{"id": "PMID:217440", "title": "Enzymic effects of beta-glucosidase destruction in mice. Changes in glucuronidase levels.", "content": "1. The injection into mice of a single dose of conduritol B epoxide, a covalent inhibitor of glucosidases, quickly produced changes in tissue levels of beta-D-glucuronidase (EC 3.2.1.31). The specific activity of the enzyme decreased in liver, spleen and kidney while brain showed little change. The inhibitor did not act on glucuronidase in vitro, so the effect of the inhibitor is complex, possibly a result of the loss of glucosidase activity. Since glucuronidase contains glucose, we suggest that the transport of the enzyme between subcellular regions and tissues involves loss of part of the glucose moieties. 2. Levels of glucocerebrosidase (D-glucosyl-N-acylsphingosine glucohydrolase, EC 3.2.1.45) dropped very rapidly after epoxide injection, reaching a minimum at 1 h in liver. There was a noticeable restoration of activity within the next 1--2 h. Aryl beta-glucosidase (EC 3.2.1.21) decrease somewhat less than cerebrosidase, reaching a minimum within 2 h. It too showed some recovery of activity within 3 h. 3. Acid phosphatase rose slightly in liver but not in brain. alpha-L-Fucosidase and angiotensin-converting enzyme were not affected by the epoxide injection. The latter two enzymes are known to contain glucose. 4. Injection of a hemolyzing agent, phenylhydrazine, produced an increased level of glucuronidase in liver and spleen within 6 days, but not in kidney. This enhancement was a little less in mice previously injected with the glucosidase inhibitor. 5. Mice injected with the epoxide once a day eight times showed a distinct rise in brain glucuronidase level, as well as a rise in brain weight. However, the other organs showed only the same decrease in glucuronidase specific activity noted with the single injection protocol. It is suggested that the difference is due to the blood-brain barrier, which could slow the loss of brain glucuronidase from the extracellular fluid.", "contents": "Enzymic effects of beta-glucosidase destruction in mice. Changes in glucuronidase levels. 1. The injection into mice of a single dose of conduritol B epoxide, a covalent inhibitor of glucosidases, quickly produced changes in tissue levels of beta-D-glucuronidase (EC 3.2.1.31). The specific activity of the enzyme decreased in liver, spleen and kidney while brain showed little change. The inhibitor did not act on glucuronidase in vitro, so the effect of the inhibitor is complex, possibly a result of the loss of glucosidase activity. Since glucuronidase contains glucose, we suggest that the transport of the enzyme between subcellular regions and tissues involves loss of part of the glucose moieties. 2. Levels of glucocerebrosidase (D-glucosyl-N-acylsphingosine glucohydrolase, EC 3.2.1.45) dropped very rapidly after epoxide injection, reaching a minimum at 1 h in liver. There was a noticeable restoration of activity within the next 1--2 h. Aryl beta-glucosidase (EC 3.2.1.21) decrease somewhat less than cerebrosidase, reaching a minimum within 2 h. It too showed some recovery of activity within 3 h. 3. Acid phosphatase rose slightly in liver but not in brain. alpha-L-Fucosidase and angiotensin-converting enzyme were not affected by the epoxide injection. The latter two enzymes are known to contain glucose. 4. Injection of a hemolyzing agent, phenylhydrazine, produced an increased level of glucuronidase in liver and spleen within 6 days, but not in kidney. This enhancement was a little less in mice previously injected with the glucosidase inhibitor. 5. Mice injected with the epoxide once a day eight times showed a distinct rise in brain glucuronidase level, as well as a rise in brain weight. However, the other organs showed only the same decrease in glucuronidase specific activity noted with the single injection protocol. It is suggested that the difference is due to the blood-brain barrier, which could slow the loss of brain glucuronidase from the extracellular fluid."}
{"id": "PMID:217442", "title": "Soluble cyclic AMP-dependent protein kinases from chick kidney. Effects of dilution and non-protein inhibitors.", "content": "Cyclic AMP-dependent protein kinases prepared from crude cytosols of chick kidney, rat kidney and rat liver were found on dilution to exhibit complex kinetics. Dilution of the cytosols appears to increase the state of activation of the enzymes. This effect was due to the presence of inhibitory agents in the cytosol which had a greater inhibitory effect on the cyclic AMP-dependent than on the cyclic AMP-independent enzyme. Two types of inhibitory activity were found by column chromatography, one resistant to trichloroacetic acid precipitation and boiling but affected by trypsin digestion and the other resistant to boiling and trypsin digestion but precipitated by trichloroacetic acid. Inhibitory activity corresponding to the former characteristics has been described previously but the presence of additional soluble inhibitory agents in the cytosol has not been documented. The complete characterisation of this previously undescribed inhibitory activity requires further investigation. The relevance of such cytosolic inhibitory activity to the interpretation of states of activation of protein kinase enzymes is discussed.", "contents": "Soluble cyclic AMP-dependent protein kinases from chick kidney. Effects of dilution and non-protein inhibitors. Cyclic AMP-dependent protein kinases prepared from crude cytosols of chick kidney, rat kidney and rat liver were found on dilution to exhibit complex kinetics. Dilution of the cytosols appears to increase the state of activation of the enzymes. This effect was due to the presence of inhibitory agents in the cytosol which had a greater inhibitory effect on the cyclic AMP-dependent than on the cyclic AMP-independent enzyme. Two types of inhibitory activity were found by column chromatography, one resistant to trichloroacetic acid precipitation and boiling but affected by trypsin digestion and the other resistant to boiling and trypsin digestion but precipitated by trichloroacetic acid. Inhibitory activity corresponding to the former characteristics has been described previously but the presence of additional soluble inhibitory agents in the cytosol has not been documented. The complete characterisation of this previously undescribed inhibitory activity requires further investigation. The relevance of such cytosolic inhibitory activity to the interpretation of states of activation of protein kinase enzymes is discussed."}
{"id": "PMID:217443", "title": "Decreased number of beta-adrenergic receptors in hypertensive vessels.", "content": "Responsiveness to inotropic agents is altered in hypertension and may contribute to its initiation and maintenance. A biochemical basis for this change was provided by the observation that the number of beta-adrenergic receptors, as reflected in specific [3H]dihydroalprenolol binding, was diminished in both arteries and veins of spontaneously hypertensive rats. There was no change in the affinity of dihydroalprenolol for the binding sites or in the capacity of isoproterenol to displace dihydroalprenolol. The decline in beta-adrenergic receptor numbers is not secondary to blood pressure elevation but may, instead, contribute to the pathogenesis of hypertension.", "contents": "Decreased number of beta-adrenergic receptors in hypertensive vessels. Responsiveness to inotropic agents is altered in hypertension and may contribute to its initiation and maintenance. A biochemical basis for this change was provided by the observation that the number of beta-adrenergic receptors, as reflected in specific [3H]dihydroalprenolol binding, was diminished in both arteries and veins of spontaneously hypertensive rats. There was no change in the affinity of dihydroalprenolol for the binding sites or in the capacity of isoproterenol to displace dihydroalprenolol. The decline in beta-adrenergic receptor numbers is not secondary to blood pressure elevation but may, instead, contribute to the pathogenesis of hypertension."}
{"id": "PMID:217444", "title": "Pulse-radiolytic investigations of catechols and catecholamines. II. Reactions of Tiron with oxygen radical species.", "content": "Transient spectra and kinetic data of Tiron (1,2-dihydroxybenzene-3,5-disulphonic acid) are reported, obtained after pulse-radiolytic oxidation by hydroxyl radicals (.OH), superoxide anions (O-2) or a combination of both oxygen radicals. The rate constant with .OH radicals was determined at 1.0.10(9) M-1.s-1. Contrary to a previous report (Greenstock, C.L. and Miller, R.W. (1975) Biochim. Biophys. Acta 396, 11--16), the rate constant with O-2 of 1.0.10(7) M-1.s-1 is lower by one order of magnitude; also the semiquinone absorbs at 300 nm rather than at 400 nm. The ratio of the rate constants with .OH and O-2 of 100 again demonstrates that any oxidation reaction by the latter radical is unspecific due to the more efficient reaction of .OH radicals, leading to the same products with catechol compounds.", "contents": "Pulse-radiolytic investigations of catechols and catecholamines. II. Reactions of Tiron with oxygen radical species. Transient spectra and kinetic data of Tiron (1,2-dihydroxybenzene-3,5-disulphonic acid) are reported, obtained after pulse-radiolytic oxidation by hydroxyl radicals (.OH), superoxide anions (O-2) or a combination of both oxygen radicals. The rate constant with .OH radicals was determined at 1.0.10(9) M-1.s-1. Contrary to a previous report (Greenstock, C.L. and Miller, R.W. (1975) Biochim. Biophys. Acta 396, 11--16), the rate constant with O-2 of 1.0.10(7) M-1.s-1 is lower by one order of magnitude; also the semiquinone absorbs at 300 nm rather than at 400 nm. The ratio of the rate constants with .OH and O-2 of 100 again demonstrates that any oxidation reaction by the latter radical is unspecific due to the more efficient reaction of .OH radicals, leading to the same products with catechol compounds."}
{"id": "PMID:217445", "title": "Phosphodiesterase and GTPase in rod outer segments. Kinetics in vitro.", "content": "The hydrolysis of cyclic guanosine monophosphate (cyclic GMP) and of guanosine triphosphate (GTP) by the broken rods of the frog retina after a flash of light have been studied in vitro with a constant perfusion method. The activation has an onset apparently instantaneous as observed with the existing possible time resolution of 3 s. The activation is followed by a partial inactivation that does not bring the activity back to the pre-flash level. GTP or the non-hydrolysable guanyl-5'-ylimidodiphosphate (GMP-PNP) is required for the normal light-activation of the phosphodiesterase and in its absence both the speed of activation and the sensitivity are greatly reduced. The activation speed, the sensitivity (threshold at approx. 0.00004% bleaching), and the kinetic constants do not exclude a direct role in the process of excitation for the phosphodiesterase and suggest a subsidiary but as yet undefined role for the GTPase.", "contents": "Phosphodiesterase and GTPase in rod outer segments. Kinetics in vitro. The hydrolysis of cyclic guanosine monophosphate (cyclic GMP) and of guanosine triphosphate (GTP) by the broken rods of the frog retina after a flash of light have been studied in vitro with a constant perfusion method. The activation has an onset apparently instantaneous as observed with the existing possible time resolution of 3 s. The activation is followed by a partial inactivation that does not bring the activity back to the pre-flash level. GTP or the non-hydrolysable guanyl-5'-ylimidodiphosphate (GMP-PNP) is required for the normal light-activation of the phosphodiesterase and in its absence both the speed of activation and the sensitivity are greatly reduced. The activation speed, the sensitivity (threshold at approx. 0.00004% bleaching), and the kinetic constants do not exclude a direct role in the process of excitation for the phosphodiesterase and suggest a subsidiary but as yet undefined role for the GTPase."}
{"id": "PMID:217446", "title": "beta-Adrenergic and muscarinic cholinergic receptors in rat submaxillary glands. Effects of thyroidectomy.", "content": "Administration of triiodothyronine to thyroidectomized rats increased the density of beta-adrenergic receptors in rat submaxillary gland without significantly changing the density of muscarinic cholinergic receptors. Thus, thyroid hormone appears to regulate beta-adrenergic sensitivity in the rat salivary gland.", "contents": "beta-Adrenergic and muscarinic cholinergic receptors in rat submaxillary glands. Effects of thyroidectomy. Administration of triiodothyronine to thyroidectomized rats increased the density of beta-adrenergic receptors in rat submaxillary gland without significantly changing the density of muscarinic cholinergic receptors. Thus, thyroid hormone appears to regulate beta-adrenergic sensitivity in the rat salivary gland."}
{"id": "PMID:217447", "title": "Glucose activation of liver glycogen synthase. Insulin-mediated restoration of glucose effect in diabetic rats is blocked by protein synthesis inhibitor.", "content": "The loss of glucose regulation of glycogen synthase in perfused livers from diabetic rats was associated with a substantial reduction in synthase phosphatase activity. Treatment of diabetic rats with insulin alone resulted in total restoration of the glucose effect and synthase phosphatase activity, while simultaneous treatment with cycloheximide severely reduced the hormonal effect. Although treatment of normal rats with cycloheximide had no effect on glucose activation of synthase, it did result in severe depletion of liver glycogen, increased liver glycogen phosphorylase activity, and elevation of liver adenosine 3',5'-monophosphate (cyclic AMP), but without elevation of liver protein kinase activity. Simultaneous treatment of alloxan-diabetic rats with insulin and cycloheximide resulted in reduction of total liver glycogen, increased phosphorylase activity, a reduction in the ability of insulin to lower hepatic cyclic AMP, and a further reduction of protein kinase activity. In summary, the effect of insulin treatment of diabetic rats to restore glucose regulation of hepatic glycogen synthase probably involves synthesis of new protein, and the data remain consistent with the hypothesis that the defect may be due to a diabetes-related deficiency in a specific synthase phosphatase and/or alteration of the synthase molecule itself.", "contents": "Glucose activation of liver glycogen synthase. Insulin-mediated restoration of glucose effect in diabetic rats is blocked by protein synthesis inhibitor. The loss of glucose regulation of glycogen synthase in perfused livers from diabetic rats was associated with a substantial reduction in synthase phosphatase activity. Treatment of diabetic rats with insulin alone resulted in total restoration of the glucose effect and synthase phosphatase activity, while simultaneous treatment with cycloheximide severely reduced the hormonal effect. Although treatment of normal rats with cycloheximide had no effect on glucose activation of synthase, it did result in severe depletion of liver glycogen, increased liver glycogen phosphorylase activity, and elevation of liver adenosine 3',5'-monophosphate (cyclic AMP), but without elevation of liver protein kinase activity. Simultaneous treatment of alloxan-diabetic rats with insulin and cycloheximide resulted in reduction of total liver glycogen, increased phosphorylase activity, a reduction in the ability of insulin to lower hepatic cyclic AMP, and a further reduction of protein kinase activity. In summary, the effect of insulin treatment of diabetic rats to restore glucose regulation of hepatic glycogen synthase probably involves synthesis of new protein, and the data remain consistent with the hypothesis that the defect may be due to a diabetes-related deficiency in a specific synthase phosphatase and/or alteration of the synthase molecule itself."}
{"id": "PMID:217448", "title": "Production of cyclic AMP from extracellular ATP by intact LM cells.", "content": "Intact LM cells, a line of cultured mouse fibroblasts, exhibited an adenylate cyclase (ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1) activity in the presence of exogenous [alpha-32P]ATP which was 20--30% of that observed with comparable preparations of lysed cells. The extent of NaF and prostaglandin E1 stimulation was comparable in intact cells and lysed cells. 96% of the added ATP and 92% of the cyclic AMP produced by intact cells could be isolated extracellularly in the incubation medium. Cellular integrity under assay conditions was monitored by trypan blue exclusion. These data suggest that LM cells contain an adenylate cyclase activity which is accessible to extracellular ATP.", "contents": "Production of cyclic AMP from extracellular ATP by intact LM cells. Intact LM cells, a line of cultured mouse fibroblasts, exhibited an adenylate cyclase (ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1) activity in the presence of exogenous [alpha-32P]ATP which was 20--30% of that observed with comparable preparations of lysed cells. The extent of NaF and prostaglandin E1 stimulation was comparable in intact cells and lysed cells. 96% of the added ATP and 92% of the cyclic AMP produced by intact cells could be isolated extracellularly in the incubation medium. Cellular integrity under assay conditions was monitored by trypan blue exclusion. These data suggest that LM cells contain an adenylate cyclase activity which is accessible to extracellular ATP."}
{"id": "PMID:217449", "title": "The regulatory effects of growth rate and cyclic AMP levels on carbon catabolism and respiration in Escherichia coli K-12.", "content": "Cyclic AMP levels in glucose and succinate-limited and ammonia-limited glucose-containing continuous cultures of Escherichia coli were measured at different bacterial growth rates. Intracellular cyclic AMP concentrations were fairly constant (about 5 micrometer) at all dilution rates used when glucose was limiting. In ammonia-limited glucose cultures the cyclic AMP content was much lower (about 0.3 micrometer). In succinate-limited cultures cyclic AMP levels fell from 2.7 to 0.8 micrometer as dilution rate increased from 0.05 to 0.4 h-1. The effects of cyclic AMP on respiratory and carbon catabolic enzyme levels were studied. There was no indication of a direct cyclic AMP involvement in the regulation of these cellular functions. It seems more likely that the variations in enzyme levels observed resulted from variation of the specific growth rate of cultures.", "contents": "The regulatory effects of growth rate and cyclic AMP levels on carbon catabolism and respiration in Escherichia coli K-12. Cyclic AMP levels in glucose and succinate-limited and ammonia-limited glucose-containing continuous cultures of Escherichia coli were measured at different bacterial growth rates. Intracellular cyclic AMP concentrations were fairly constant (about 5 micrometer) at all dilution rates used when glucose was limiting. In ammonia-limited glucose cultures the cyclic AMP content was much lower (about 0.3 micrometer). In succinate-limited cultures cyclic AMP levels fell from 2.7 to 0.8 micrometer as dilution rate increased from 0.05 to 0.4 h-1. The effects of cyclic AMP on respiratory and carbon catabolic enzyme levels were studied. There was no indication of a direct cyclic AMP involvement in the regulation of these cellular functions. It seems more likely that the variations in enzyme levels observed resulted from variation of the specific growth rate of cultures."}
{"id": "PMID:217450", "title": "The heparan sulfates of Swiss mouse 3T3 cells. The effect of transformation.", "content": "Three major pools of heparan sulfate have been isolated from cultures of Swiss mouse 3T3 and SV40-transformed 3T3 cells: cell-surface, medium, and intracellular heparan sulfates. The cell-surface heparan sulfate is a high molecular weight proteoglycan which is partially degraded by pronase. Before pronase treatment, it has a peak molecular weight (as estimated by gel filtration) of approx. 7.2 . 10(5) in contrast to only 2.4 . 10(5) after pronase treatment. The medium heparan sulfate appears to be similar in structure to the cell-surface heparan sulfate, since they coelute on Bio-Gel A-15m and DEAE-cellulose, and are both proteoglycans. In contrast, the intracellular heparan sulfate has a low molecular weight (6.0 . 10(3)) and has little if any attached protein. Both the medium and intracellular heparan sulfate exhibit the transformation-associated change in structure reported earlier for cell-surface heparan sulfate (Underhill, C.B. and Keller, J.M. )1975) Biochem. Biophys. Res. Commun. 63, 448--454). This transformation-associated change, detected by DEAE-cellulose chromatography is not the result of changes in either molecular weight or protein core. Cellulose acetate electrophoresis of the cell-surface heparan sulfate at pH 1 suggests that the transformation-associated change in structure is due to a difference in sulfate content. Both types of heparan sulfate are produced in mixed cultures of 3T3 and SV3T3 cells, indicating that neither serum factors in the culture medium nor secreted cell products are responsible for the transformation-associated change in heparan sulfate structure. The presented data are discussed with respect to the postulated role of heparan sulfate in cell social behavior.", "contents": "The heparan sulfates of Swiss mouse 3T3 cells. The effect of transformation. Three major pools of heparan sulfate have been isolated from cultures of Swiss mouse 3T3 and SV40-transformed 3T3 cells: cell-surface, medium, and intracellular heparan sulfates. The cell-surface heparan sulfate is a high molecular weight proteoglycan which is partially degraded by pronase. Before pronase treatment, it has a peak molecular weight (as estimated by gel filtration) of approx. 7.2 . 10(5) in contrast to only 2.4 . 10(5) after pronase treatment. The medium heparan sulfate appears to be similar in structure to the cell-surface heparan sulfate, since they coelute on Bio-Gel A-15m and DEAE-cellulose, and are both proteoglycans. In contrast, the intracellular heparan sulfate has a low molecular weight (6.0 . 10(3)) and has little if any attached protein. Both the medium and intracellular heparan sulfate exhibit the transformation-associated change in structure reported earlier for cell-surface heparan sulfate (Underhill, C.B. and Keller, J.M. )1975) Biochem. Biophys. Res. Commun. 63, 448--454). This transformation-associated change, detected by DEAE-cellulose chromatography is not the result of changes in either molecular weight or protein core. Cellulose acetate electrophoresis of the cell-surface heparan sulfate at pH 1 suggests that the transformation-associated change in structure is due to a difference in sulfate content. Both types of heparan sulfate are produced in mixed cultures of 3T3 and SV3T3 cells, indicating that neither serum factors in the culture medium nor secreted cell products are responsible for the transformation-associated change in heparan sulfate structure. The presented data are discussed with respect to the postulated role of heparan sulfate in cell social behavior."}
{"id": "PMID:217451", "title": "[Aminoglycoside-3'-phosphotransferase I from aminoglycoside-polyresistant strain E. coli 182].", "content": "An aminoglycoside-3'-phosphotransferase I catalyzing phosphorylation of some aminoglycoside antibiotics with the 3'-hydroxyl group has been purified from the cells of aminoglycoside resistant strain E. coli 182 by competitive affinity chromatography on neomycin-Sepharose and gel-filtration on Sephadex G-100. The product of enzymatic phosphorylation of kanamycin A was isolated and identified as kanamycin-3'-phosphate by NMR, thin-layer chromatography and chemical characterization. The kinetic properties of the enzyme were studied. The pH-optimum was between 7,8--8,0; the [S]0.5 values for kanamycin, neomycin and paromomycin were 2.10(-5) M, the energy of activation was 15,9 kcal/mol. The bivalent cations were required for activity of the enzyme, Mg2+ was the most effecient. The relative aminoglycoside antibiotics containing no 3'-hydroxyl group were competitive inhibitors of the enzyme activity with Ki values close to [S]0.5.", "contents": "[Aminoglycoside-3'-phosphotransferase I from aminoglycoside-polyresistant strain E. coli 182]. An aminoglycoside-3'-phosphotransferase I catalyzing phosphorylation of some aminoglycoside antibiotics with the 3'-hydroxyl group has been purified from the cells of aminoglycoside resistant strain E. coli 182 by competitive affinity chromatography on neomycin-Sepharose and gel-filtration on Sephadex G-100. The product of enzymatic phosphorylation of kanamycin A was isolated and identified as kanamycin-3'-phosphate by NMR, thin-layer chromatography and chemical characterization. The kinetic properties of the enzyme were studied. The pH-optimum was between 7,8--8,0; the [S]0.5 values for kanamycin, neomycin and paromomycin were 2.10(-5) M, the energy of activation was 15,9 kcal/mol. The bivalent cations were required for activity of the enzyme, Mg2+ was the most effecient. The relative aminoglycoside antibiotics containing no 3'-hydroxyl group were competitive inhibitors of the enzyme activity with Ki values close to [S]0.5."}
{"id": "PMID:217452", "title": "[Substrate and inhibitory specificity of riboflavin kinase from Pichia guilliermondii yeast].", "content": "The interaction of purified riboflavin kinase (EC 2.7.1.26) from Pichia guilliermondii with 44 structural vitamin B2 analogues is studied. The presence of D-ribityl lateral chain in an analogue structure is found to be necessary for the substrate activity. The substitution of CH3 groups in the 7 and 8 positions of isoalloxazine ring in the riboflavin molecule for CF3, Cl, H, NH2 and N(CH3)2 resulted in the decrease of the analogue affinity to riboflavin kinase as compared with the natural substrate, vitamin B2. The most efficient enzyme inhibitors of analogues without substrate properties turned to be trifluoromethylisoalloxazines, containing 2'-hydroxyethyl group at N10. The elongation of D-ribityl lateral chain, the elimination of change of CH3-groups in the 7 and 8 positions for CF3- Cl-, COOH-substitutors resulted in the decrease of the inhibitory effect of flavines. Modifications in the structure of isoalloxazine ring, etherification of OH-groups in the lateral D-ribityl chain, and the introduction of volume substitutors (N-piperidyl, D-ribitylamine, hydroxyethylamine) prevented the interaction of the analogue with riboflavin kinase. Flavin nucleotides (FMN and FAD) did not affect the rate of vitamin B2 phosphorylation.", "contents": "[Substrate and inhibitory specificity of riboflavin kinase from Pichia guilliermondii yeast]. The interaction of purified riboflavin kinase (EC 2.7.1.26) from Pichia guilliermondii with 44 structural vitamin B2 analogues is studied. The presence of D-ribityl lateral chain in an analogue structure is found to be necessary for the substrate activity. The substitution of CH3 groups in the 7 and 8 positions of isoalloxazine ring in the riboflavin molecule for CF3, Cl, H, NH2 and N(CH3)2 resulted in the decrease of the analogue affinity to riboflavin kinase as compared with the natural substrate, vitamin B2. The most efficient enzyme inhibitors of analogues without substrate properties turned to be trifluoromethylisoalloxazines, containing 2'-hydroxyethyl group at N10. The elongation of D-ribityl lateral chain, the elimination of change of CH3-groups in the 7 and 8 positions for CF3- Cl-, COOH-substitutors resulted in the decrease of the inhibitory effect of flavines. Modifications in the structure of isoalloxazine ring, etherification of OH-groups in the lateral D-ribityl chain, and the introduction of volume substitutors (N-piperidyl, D-ribitylamine, hydroxyethylamine) prevented the interaction of the analogue with riboflavin kinase. Flavin nucleotides (FMN and FAD) did not affect the rate of vitamin B2 phosphorylation."}
{"id": "PMID:217453", "title": "[Activities of enzymes from canine kidney plasma membranes under effects of polyene antibiotics in vivo and in vitro].", "content": "The effects of amphotericin B drug containing sodium deoxycholate (DOC) and those of DOC and nistatin on the activities of Na+, K+-ATPase and 5'-nucleotidase of canine kidney plasma membranes were studied. It was found that the activities of Na+, K+-ATPase and 5'-nucleotidase were markedly inhibited only after intravenous injection of amphotericin B, whereas the other agents tested caused no changes in the enzyme activities. Similar results were obtained in vitro. In the presence of amphotericin B the activity of Na+, K+-ATPase was noticeably inhibited already at the antibiotic concentration of 0,1 mkg per mg of membrane protein. It was found that the injection of amphotericin B, DOC and nistatin did not qualitatively or quantitatively affect the phospholipid composition of the plasma membranes. This is indicative of the lack of correlation between the enzyme activities and changes in the phospholipid composition of the plasma membranes under effects of amphotericin B. The pyrimidine derivative--amygluracyl--markedly removes the inhibiting effect of amphotericin B on the enzyme activity of plasma membranes.", "contents": "[Activities of enzymes from canine kidney plasma membranes under effects of polyene antibiotics in vivo and in vitro]. The effects of amphotericin B drug containing sodium deoxycholate (DOC) and those of DOC and nistatin on the activities of Na+, K+-ATPase and 5'-nucleotidase of canine kidney plasma membranes were studied. It was found that the activities of Na+, K+-ATPase and 5'-nucleotidase were markedly inhibited only after intravenous injection of amphotericin B, whereas the other agents tested caused no changes in the enzyme activities. Similar results were obtained in vitro. In the presence of amphotericin B the activity of Na+, K+-ATPase was noticeably inhibited already at the antibiotic concentration of 0,1 mkg per mg of membrane protein. It was found that the injection of amphotericin B, DOC and nistatin did not qualitatively or quantitatively affect the phospholipid composition of the plasma membranes. This is indicative of the lack of correlation between the enzyme activities and changes in the phospholipid composition of the plasma membranes under effects of amphotericin B. The pyrimidine derivative--amygluracyl--markedly removes the inhibiting effect of amphotericin B on the enzyme activity of plasma membranes."}
{"id": "PMID:217454", "title": "[Mechanisms of rat liver thiamine pyrophosphokinase activation by magnesium ions].", "content": "The role of Mg2+ in the activation of thiamine pyrophosphokinase from rat liver was studied. The dependence of the thiamine pyrophosphokinase reaction rate on total and free ATP concentrations suggests that the role of the metal comes down to optimization of conditions of the active enzyme-substrate complex formation due to incorporation of the reactions of Mg2+ and ATP-4 consecutive acception, the affinity of the latter for the enzyme being higher than that of Mg-ATP-2. The kinetic parameters of the reaction were determined. In the absence of ATP-4 free Mg2+ ions were shown to compete with the Mg-ATP-2 complex (Ki = 18 . 10(-3) M). Thiamine pyrophosphokinase is also inhibited by free ATP-4 with Ki = 3 . 10(-3) M.", "contents": "[Mechanisms of rat liver thiamine pyrophosphokinase activation by magnesium ions]. The role of Mg2+ in the activation of thiamine pyrophosphokinase from rat liver was studied. The dependence of the thiamine pyrophosphokinase reaction rate on total and free ATP concentrations suggests that the role of the metal comes down to optimization of conditions of the active enzyme-substrate complex formation due to incorporation of the reactions of Mg2+ and ATP-4 consecutive acception, the affinity of the latter for the enzyme being higher than that of Mg-ATP-2. The kinetic parameters of the reaction were determined. In the absence of ATP-4 free Mg2+ ions were shown to compete with the Mg-ATP-2 complex (Ki = 18 . 10(-3) M). Thiamine pyrophosphokinase is also inhibited by free ATP-4 with Ki = 3 . 10(-3) M."}
{"id": "PMID:217455", "title": "[Melting and reassociation of double-stranded RNA of the encephalomyocarditis virus].", "content": "The processes of melting and reassociation of double-stranded RNA in dimethylsulfoxide were studied. The addition of a small amount of LiCl results in great results in great reduction of Tm (temperature of melting), whereas the NaCl produces the opposite effect. It is suggested, that LiCl coordinates the molecules of H2O, reducing their activity, and consequently destabilises dsRNA. Mild conditions for melting and reassociation of RNA can be created. It was found that under optimal conditions for dsRNA melting, the degree of strand separation depends on the overall concentration of RNA, irrespective of the type of RNA added to the dsRNA preparation. Reassociation of dsRNA of EMC virus proceeds much faster than that of dsRNA of a related poliovirus. Addition of poly(C) to an annealing mixture slows down the rate of reassociation of EMC dsRNA, producing no effect on the poliovirus dsRNA reassociation. It is suggested that the presence of large poly(C) and poly(G) tracts in the complementary strands of the RNA determines its anomalous fast reassociation. Upon incubation of completely separated strands of EMC dsRNA in a water solution with high ionic strength partially double-stranded aggregates are formed. The formation of aggregates is prevented by addition of poly(A), which indicates that they are produced by \"zippening\" of a molecule starting with poly(A):poly(U) region. The significance of homopolymeric regions for stability of dsRNA of the EMC virus as well as their role in viral multiplication are discussed.", "contents": "[Melting and reassociation of double-stranded RNA of the encephalomyocarditis virus]. The processes of melting and reassociation of double-stranded RNA in dimethylsulfoxide were studied. The addition of a small amount of LiCl results in great results in great reduction of Tm (temperature of melting), whereas the NaCl produces the opposite effect. It is suggested, that LiCl coordinates the molecules of H2O, reducing their activity, and consequently destabilises dsRNA. Mild conditions for melting and reassociation of RNA can be created. It was found that under optimal conditions for dsRNA melting, the degree of strand separation depends on the overall concentration of RNA, irrespective of the type of RNA added to the dsRNA preparation. Reassociation of dsRNA of EMC virus proceeds much faster than that of dsRNA of a related poliovirus. Addition of poly(C) to an annealing mixture slows down the rate of reassociation of EMC dsRNA, producing no effect on the poliovirus dsRNA reassociation. It is suggested that the presence of large poly(C) and poly(G) tracts in the complementary strands of the RNA determines its anomalous fast reassociation. Upon incubation of completely separated strands of EMC dsRNA in a water solution with high ionic strength partially double-stranded aggregates are formed. The formation of aggregates is prevented by addition of poly(A), which indicates that they are produced by \"zippening\" of a molecule starting with poly(A):poly(U) region. The significance of homopolymeric regions for stability of dsRNA of the EMC virus as well as their role in viral multiplication are discussed."}
{"id": "PMID:217456", "title": "Hormonal regulation of three urea cycle enzymes in rat fetal liver.", "content": "The purpose of such studies is to identify the hormones that act on the developmental formation of individual urea cycle enzymes, namely argininosuccinate synthetase, argininosuccinate lyase and arginase in the rat fetal liver. The development of argininosuccinate synthetase activity which is completely blocked by the suppression of glucocorticoids in the fetal liver is affected by neither glucagon nor thyroxine. The activity of argininosuccinate lyase which is never changed by the suppression or addition of glucocorticoids, is under the influences of glucagon and thyroxine at a late fetal period and the enzyme activity can be precociously induced in utero by injection of dibutyryl cyclic AMP to fetuses. Cortisol has been shown to precociously stimulate fetal liver arginase activity after an intraperitoneal injection, but the rise in activity at the late fetal period is not completely prevented by suppression of glucocorticoid and it seems that glucagon and thyroxine may also promote its developmental formation just before birth.", "contents": "Hormonal regulation of three urea cycle enzymes in rat fetal liver. The purpose of such studies is to identify the hormones that act on the developmental formation of individual urea cycle enzymes, namely argininosuccinate synthetase, argininosuccinate lyase and arginase in the rat fetal liver. The development of argininosuccinate synthetase activity which is completely blocked by the suppression of glucocorticoids in the fetal liver is affected by neither glucagon nor thyroxine. The activity of argininosuccinate lyase which is never changed by the suppression or addition of glucocorticoids, is under the influences of glucagon and thyroxine at a late fetal period and the enzyme activity can be precociously induced in utero by injection of dibutyryl cyclic AMP to fetuses. Cortisol has been shown to precociously stimulate fetal liver arginase activity after an intraperitoneal injection, but the rise in activity at the late fetal period is not completely prevented by suppression of glucocorticoid and it seems that glucagon and thyroxine may also promote its developmental formation just before birth."}
{"id": "PMID:217457", "title": "Effect of certain cerebral hemispheric diseases on dreaming.", "content": "Dreaming may be altered by cerebral hemispheric disease. A woman who sustained a probable left posterior cerebral artery thrombosis, with right homonymous hemianopsia and alexia, had virtual cessation of dreaming for at least 9 months. Four individuals with temporal lobe epilepsy experienced recurrent painful (frightening) dreams, which in two patients showed features identical to seizures. Sleep recordings showed abnormalities in all four, including rhythmic temporal epileptiform activity during REM sleep. Lesions in parieto-occipital loci may interfere with production of the visual imagery required for dreaming (negative symptom in the Jacksonian sense) while epileptic activity in temporal loci may produce painful repetitive dream imagery (positive symptom).", "contents": "Effect of certain cerebral hemispheric diseases on dreaming. Dreaming may be altered by cerebral hemispheric disease. A woman who sustained a probable left posterior cerebral artery thrombosis, with right homonymous hemianopsia and alexia, had virtual cessation of dreaming for at least 9 months. Four individuals with temporal lobe epilepsy experienced recurrent painful (frightening) dreams, which in two patients showed features identical to seizures. Sleep recordings showed abnormalities in all four, including rhythmic temporal epileptiform activity during REM sleep. Lesions in parieto-occipital loci may interfere with production of the visual imagery required for dreaming (negative symptom in the Jacksonian sense) while epileptic activity in temporal loci may produce painful repetitive dream imagery (positive symptom)."}
{"id": "PMID:217458", "title": "Electrographic analysis of the sleep cycle in young depressed patients.", "content": "Electrographic (EEG) patterns of nocturnal sleep were investigated in young psychiatric patients during unipolar depressive episodes. EEG-sleep data was recorded in 20 non-psychotic depressed patients all under 26 years old individually matched with a normal control group. All 20 subjects slept in the laboratory for 1-3 consecutive baseline nights from 12-8:00 a.m. During a subsequent extended condition 14 in each group were allowed to sleep ad-lib. Although the mean total time asleep on baseline nights was about the same between groups (greater than 7.1 hr), the depressives had a statistically significant reduction in REM time, increased transitions into stage 1, but most especially averaged: (a) less stage 4; and (b) more stage 1. Compared with the prior eight-hour night 27/28 subjects among both groups exhibited elevated time asleep during the extended condition, but the patients' mean total 10.3 hr sleep was significantly greater by 1.5 hr than the controls (X = 8.8 hr). Sleep exceeding 9 hr on the ad-lib night was a consistent phenomenon which occurred in significantly more (11/14) young depressed patients contrasted to 4/14 control subjects. These findings indicate that young persons with primary affective disorders do not exhibit nocturnal EEG disturbances of comparable severity to most older depressed patients such as reduced time asleep, increased wakefulness or lowered slow-wave (stages 3 and 4) sleep. Although no direct evidence of symptomatic 'hypersomnia' in these patients was provided, the present results demonstrated that some young persons with clinical depression have the capacity to sleep for sustained periods.", "contents": "Electrographic analysis of the sleep cycle in young depressed patients. Electrographic (EEG) patterns of nocturnal sleep were investigated in young psychiatric patients during unipolar depressive episodes. EEG-sleep data was recorded in 20 non-psychotic depressed patients all under 26 years old individually matched with a normal control group. All 20 subjects slept in the laboratory for 1-3 consecutive baseline nights from 12-8:00 a.m. During a subsequent extended condition 14 in each group were allowed to sleep ad-lib. Although the mean total time asleep on baseline nights was about the same between groups (greater than 7.1 hr), the depressives had a statistically significant reduction in REM time, increased transitions into stage 1, but most especially averaged: (a) less stage 4; and (b) more stage 1. Compared with the prior eight-hour night 27/28 subjects among both groups exhibited elevated time asleep during the extended condition, but the patients' mean total 10.3 hr sleep was significantly greater by 1.5 hr than the controls (X = 8.8 hr). Sleep exceeding 9 hr on the ad-lib night was a consistent phenomenon which occurred in significantly more (11/14) young depressed patients contrasted to 4/14 control subjects. These findings indicate that young persons with primary affective disorders do not exhibit nocturnal EEG disturbances of comparable severity to most older depressed patients such as reduced time asleep, increased wakefulness or lowered slow-wave (stages 3 and 4) sleep. Although no direct evidence of symptomatic 'hypersomnia' in these patients was provided, the present results demonstrated that some young persons with clinical depression have the capacity to sleep for sustained periods."}
{"id": "PMID:217464", "title": "Recent data and significance of intracisternal tubular inclusions in human and animal cells.", "content": "In 24 out of 60 patients with nasopharyngeal carcinoma (NPC) the cells were shown to contain a tubulo-reticular network in the dilated cisternae of the ergastoplasm which corresponds to the entity described previously as \"intracisternal-tubular inclusion\" (ITI). The significance of such inclusions is discussed in different pathological conditions and the literature is reviewed. This is the first report of such inclusions in nasopharyngeal carcinoma.", "contents": "Recent data and significance of intracisternal tubular inclusions in human and animal cells. In 24 out of 60 patients with nasopharyngeal carcinoma (NPC) the cells were shown to contain a tubulo-reticular network in the dilated cisternae of the ergastoplasm which corresponds to the entity described previously as \"intracisternal-tubular inclusion\" (ITI). The significance of such inclusions is discussed in different pathological conditions and the literature is reviewed. This is the first report of such inclusions in nasopharyngeal carcinoma."}
{"id": "PMID:217465", "title": "Investigation of the significance of a carbon and redox balance to the measurement of gaseous metabolism of Saccharomyces cerevisiae.", "content": "A complete carbon and redox balance for Saccharomyces cerevisiae grown in batch culture with ethanol as the limiting carbon and energy source is reported. A novel method, which allowed the determination of carbon dioxide contained in the culture medium and biomass, is described and revealed amounts considerably in excess of what was expected from equilibrium data. Furthermore, elemental composition of the biomass was used to calculate the amount of oxygen required for biosynthetic reactions. When these corrections are applied to experimentally measured gas metabolism data, apparently anomalous results are shown to be consistent with the overall metabolism of bakers' yeast. These findings have wide implications to the quantitative study of the metabolism and energetics of facultative aerobes.", "contents": "Investigation of the significance of a carbon and redox balance to the measurement of gaseous metabolism of Saccharomyces cerevisiae. A complete carbon and redox balance for Saccharomyces cerevisiae grown in batch culture with ethanol as the limiting carbon and energy source is reported. A novel method, which allowed the determination of carbon dioxide contained in the culture medium and biomass, is described and revealed amounts considerably in excess of what was expected from equilibrium data. Furthermore, elemental composition of the biomass was used to calculate the amount of oxygen required for biosynthetic reactions. When these corrections are applied to experimentally measured gas metabolism data, apparently anomalous results are shown to be consistent with the overall metabolism of bakers' yeast. These findings have wide implications to the quantitative study of the metabolism and energetics of facultative aerobes."}
{"id": "PMID:217466", "title": "[State of vascular tone and several blood biochemical indices in experimental atherosclerosis and sensitization].", "content": "A study of the vascular tone of the posterior extremities in rabbits, of some blood lipid metabolism indices under conditions of experimental atherosclerosis and sensitization showed an increase in the vascular resistance in the areas investigated, and disturbance of lipid metabolism in two experimental groups of animals. The data obtained support the literature evidence that allergic component serves as one of the factors complicating the atherosclerosis course.", "contents": "[State of vascular tone and several blood biochemical indices in experimental atherosclerosis and sensitization]. A study of the vascular tone of the posterior extremities in rabbits, of some blood lipid metabolism indices under conditions of experimental atherosclerosis and sensitization showed an increase in the vascular resistance in the areas investigated, and disturbance of lipid metabolism in two experimental groups of animals. The data obtained support the literature evidence that allergic component serves as one of the factors complicating the atherosclerosis course."}
{"id": "PMID:217467", "title": "[Electron microscopic study of isolated proteoglycans].", "content": "Chemically isolated separate preparations of the non-aggregating protein-chondroitin-keratin sulphate (PCKS) fraction from the hyaline cartilage and hyaluronic acid (HUA) of the vitreous body and of the umbilicus were investigated by electron microscopy. PCKS and HUA in films without cytochrome c were present in the form of granules and differed by structural organization. The proteoglycans of the cytochrome c films were seen as finely-filamentous-cellular network, and were distinctly differentiated by their macromolecular organization. A mixture of both proteoglycans formed complexes as a result of a noncovalent interaction. Uranyl acetate ensured a good contrasting of proteoglycans, especially of PCKS, without cytochrome c.", "contents": "[Electron microscopic study of isolated proteoglycans]. Chemically isolated separate preparations of the non-aggregating protein-chondroitin-keratin sulphate (PCKS) fraction from the hyaline cartilage and hyaluronic acid (HUA) of the vitreous body and of the umbilicus were investigated by electron microscopy. PCKS and HUA in films without cytochrome c were present in the form of granules and differed by structural organization. The proteoglycans of the cytochrome c films were seen as finely-filamentous-cellular network, and were distinctly differentiated by their macromolecular organization. A mixture of both proteoglycans formed complexes as a result of a noncovalent interaction. Uranyl acetate ensured a good contrasting of proteoglycans, especially of PCKS, without cytochrome c."}
{"id": "PMID:217468", "title": "[Effect of taurine on cyclic AMP and GMP levels in the hearts of rats exposed to stress].", "content": "Taurine produced no effect on the cyclic nucleotides level in the heart of intact rats but sharply inhibited the cAMP and cGMP level elevation in the rat heart occuring in stress. After atropine pretreatment of the animals no effect of taurine on the heart cGMP level was observed; its effect on the cAMP level was significantly inhibited against the background of partial beta-adrenoreceptors block. It is suggested that taurine is a nonspecific regulator of the myocardial cells sensitivity to the biologically active drugs.", "contents": "[Effect of taurine on cyclic AMP and GMP levels in the hearts of rats exposed to stress]. Taurine produced no effect on the cyclic nucleotides level in the heart of intact rats but sharply inhibited the cAMP and cGMP level elevation in the rat heart occuring in stress. After atropine pretreatment of the animals no effect of taurine on the heart cGMP level was observed; its effect on the cAMP level was significantly inhibited against the background of partial beta-adrenoreceptors block. It is suggested that taurine is a nonspecific regulator of the myocardial cells sensitivity to the biologically active drugs."}
{"id": "PMID:217469", "title": "[Reproduction of murine encephalomyocarditis virus in enucleated Krebs 2 ascitic carcinoma cells].", "content": "Enucleated cells of ascites carcinoma Krebs 2 (cytoplasts) were prepared. The cells were centrifugated for this purpose in a discontinuous Ficoll density gradient containing cytochalasine B. The cytoplasts formed turbid bands in Phycol solution at the density of 1.037--1.053 g/ml. The cytoplasts failed to synthesize RNA, but proteins were synthesized for several hours. Encephalomyocarditis virus replicated in the ascites carcinoma cytoplasts, but its yield was 10 to 100-fold lower as compared to that in the intact cells. Apparently the reduction of the virus yield was not due to the low efficiency of early stages of the virus-cytoplast interaction. Viral infection resulted in inhibition of the synthesis of cellular proteins in the cytoplasts as well as in the intact cells.", "contents": "[Reproduction of murine encephalomyocarditis virus in enucleated Krebs 2 ascitic carcinoma cells]. Enucleated cells of ascites carcinoma Krebs 2 (cytoplasts) were prepared. The cells were centrifugated for this purpose in a discontinuous Ficoll density gradient containing cytochalasine B. The cytoplasts formed turbid bands in Phycol solution at the density of 1.037--1.053 g/ml. The cytoplasts failed to synthesize RNA, but proteins were synthesized for several hours. Encephalomyocarditis virus replicated in the ascites carcinoma cytoplasts, but its yield was 10 to 100-fold lower as compared to that in the intact cells. Apparently the reduction of the virus yield was not due to the low efficiency of early stages of the virus-cytoplast interaction. Viral infection resulted in inhibition of the synthesis of cellular proteins in the cytoplasts as well as in the intact cells."}
{"id": "PMID:217470", "title": "[Non-infiltrating intraductal carcinoma of the breast (author's transl)].", "content": "Non-infiltrating intraductal carcinoma may be considered a type of \"carcinoma in situ\" of the breast. In a review of 47 cases diagnosed and treated at Gustave-Roussy Institute between 1956--1972, it appears that the early symptoms of this rare type of breast carcinoma (it occurs only in 2.4% of all breast cancers) were a bloody discharge (38%) or Paget's disease of the nipple (11%). The histological examination was of the utmost importance in these cases due to the diagnostic uncertainties between benign hyperplastic lesions and authentic carcinomas as well as between infiltrating carcinomas and strictly intraductal carcinomas. Frozen section was only accurate in 30% of cases. The high frequency of multicentric foci (76%) contrasted with the absence of lymph node involvment (none of the 23 cases in which at least one node was excised, showed lymph node metastases). Treatment was only of ablation of the whole mammary gland, except in 6 patients who had a tumorectomy, two of whom also received radiotherapy. Local recurrence occurred in 4 patients, 3 of whom had only tumorectomy. The contralateral breast was affected in 2 cases. No patient under follow-up died of cancer within 5 years. The peculiar and highly favorable course of non-infiltrating intraductal carcinoma calls for an adequate therapy which could later be followed by a plastic reconstructive surgery should the patient wish to have this procedure.", "contents": "[Non-infiltrating intraductal carcinoma of the breast (author's transl)]. Non-infiltrating intraductal carcinoma may be considered a type of \"carcinoma in situ\" of the breast. In a review of 47 cases diagnosed and treated at Gustave-Roussy Institute between 1956--1972, it appears that the early symptoms of this rare type of breast carcinoma (it occurs only in 2.4% of all breast cancers) were a bloody discharge (38%) or Paget's disease of the nipple (11%). The histological examination was of the utmost importance in these cases due to the diagnostic uncertainties between benign hyperplastic lesions and authentic carcinomas as well as between infiltrating carcinomas and strictly intraductal carcinomas. Frozen section was only accurate in 30% of cases. The high frequency of multicentric foci (76%) contrasted with the absence of lymph node involvment (none of the 23 cases in which at least one node was excised, showed lymph node metastases). Treatment was only of ablation of the whole mammary gland, except in 6 patients who had a tumorectomy, two of whom also received radiotherapy. Local recurrence occurred in 4 patients, 3 of whom had only tumorectomy. The contralateral breast was affected in 2 cases. No patient under follow-up died of cancer within 5 years. The peculiar and highly favorable course of non-infiltrating intraductal carcinoma calls for an adequate therapy which could later be followed by a plastic reconstructive surgery should the patient wish to have this procedure."}
{"id": "PMID:217471", "title": "[Differences in the fixation of antibodies in presence or absence of complement on SV40 transformed cells (author's transl)].", "content": "The fixation of antibodies directed against viral induced antigens was observed on SV40 transformed hamster fibroblasts. These cells were incubated for various periods of time with sera of tumor bearing hamster in the presence or absence of fresh guinea pig complement. The fixation of antibodies was revealed by an anti hamster immunoglobulins immune serum labeled with 125 iodine. Autoradiographic observations were made by optic and electron microscopy. The fixation of antibodies is quite different in the presence or in the absence of complement. Cells incubated with antibodies alone show a regular label on the plasma membrane with no decrease in the total cell population as compared to the controls. When the complement is added, one fraction of the cells is heavily labeled detached and progressively destroyed. Some of the cells (2/10) still attached on the flask are heavily labeled on the plasma membrane, the major part being nearly negative.", "contents": "[Differences in the fixation of antibodies in presence or absence of complement on SV40 transformed cells (author's transl)]. The fixation of antibodies directed against viral induced antigens was observed on SV40 transformed hamster fibroblasts. These cells were incubated for various periods of time with sera of tumor bearing hamster in the presence or absence of fresh guinea pig complement. The fixation of antibodies was revealed by an anti hamster immunoglobulins immune serum labeled with 125 iodine. Autoradiographic observations were made by optic and electron microscopy. The fixation of antibodies is quite different in the presence or in the absence of complement. Cells incubated with antibodies alone show a regular label on the plasma membrane with no decrease in the total cell population as compared to the controls. When the complement is added, one fraction of the cells is heavily labeled detached and progressively destroyed. Some of the cells (2/10) still attached on the flask are heavily labeled on the plasma membrane, the major part being nearly negative."}
{"id": "PMID:217477", "title": "Visual receptive fields of units in the pulvinar of cebus monkey.", "content": "Visually driven units, isolated in the ventrolateral group -- Pv1g (109) and in subnucleus Pmu (33) of the pulvinar of the cebus monkey, were studied in acute and chronic preparations under nitrous oxide N2O/O2 anesthesia during periods of EEG arousal. Taking into consideration the response properties to static or moving stimuli as well as the organization of the receptive fields, units isolated in the pulvinar were subdivided into 8 groups. Units displaying dynamic properties predominate over static ones. Static units were classified in 3 groups; of these, one showed uniform receptive fields; the remaining two groups, with non-uniform RFs, were further subdivided in terms of orientation selectivity. By testing for directional sensitivity, organization of the RFs and orientation selectivity, the dynamic units were divided in 5 groups. Among these there was a predominance of directional units, displaying uniform RFs and showing orientation selectivity. Although the receptive fields would extend into the ipsilateral hemifield (up to 10 degrees), their centers were always located in the contralateral visual hemifield. Binocularly driven units predominate in both static and dynamic categories.", "contents": "Visual receptive fields of units in the pulvinar of cebus monkey. Visually driven units, isolated in the ventrolateral group -- Pv1g (109) and in subnucleus Pmu (33) of the pulvinar of the cebus monkey, were studied in acute and chronic preparations under nitrous oxide N2O/O2 anesthesia during periods of EEG arousal. Taking into consideration the response properties to static or moving stimuli as well as the organization of the receptive fields, units isolated in the pulvinar were subdivided into 8 groups. Units displaying dynamic properties predominate over static ones. Static units were classified in 3 groups; of these, one showed uniform receptive fields; the remaining two groups, with non-uniform RFs, were further subdivided in terms of orientation selectivity. By testing for directional sensitivity, organization of the RFs and orientation selectivity, the dynamic units were divided in 5 groups. Among these there was a predominance of directional units, displaying uniform RFs and showing orientation selectivity. Although the receptive fields would extend into the ipsilateral hemifield (up to 10 degrees), their centers were always located in the contralateral visual hemifield. Binocularly driven units predominate in both static and dynamic categories."}
{"id": "PMID:217478", "title": "Effects of intraventricular injection of 6-hydroxydopamine in the developing kitten. 1. On the sleepwaking cycles.", "content": "Intraventricular 6-OHDA was injected in kittens at different stages of development, and the subsequent sleep polygram was analyzed, in order to determine the role of the catecholaminergic system in the ontogenesis of sleep regulations during the first and the second postnatal months. 6-OHDA, used with or without previous chlorimipramine treatment, led within a 10-day period to drastic reductions of the endogenous monoamines in the forebrain of all age groups. Although the neurotoxicity of 6-OHDA was almost constant among the different age groups, the effects on sleep depended on the age of the animals at the time of the injection. In the 5-week-old injected kittens, 6-OHDA affected PS according to an adult-like pattern. In the 3-week-old kittens, 6-OHDA alone (leading to both catecholamines and serotonin decreases) induced the same PS deficit as in the adult cat. In the 1- and 2-week-old kittens, neither 6-OHDA alone, nor 6-OHDA with previous chlorimipramine treatment, distrubed the sleep regulations. These data are compared to similar experiments performed in the adult cat. They are discussed in terms of sleep control ontogenesis. It is concluded that the catecholaminergic system plays no important role in the mechanisms of sleep regulation in the early postnatal period in the kitten, whereas its regulatory influence on PS is confirmed in the juvenile animal. The functional maturation of the catecholaminergic system in terms of sleep regulation is achieved between the third and the fifth week of postnatal life.", "contents": "Effects of intraventricular injection of 6-hydroxydopamine in the developing kitten. 1. On the sleepwaking cycles. Intraventricular 6-OHDA was injected in kittens at different stages of development, and the subsequent sleep polygram was analyzed, in order to determine the role of the catecholaminergic system in the ontogenesis of sleep regulations during the first and the second postnatal months. 6-OHDA, used with or without previous chlorimipramine treatment, led within a 10-day period to drastic reductions of the endogenous monoamines in the forebrain of all age groups. Although the neurotoxicity of 6-OHDA was almost constant among the different age groups, the effects on sleep depended on the age of the animals at the time of the injection. In the 5-week-old injected kittens, 6-OHDA affected PS according to an adult-like pattern. In the 3-week-old kittens, 6-OHDA alone (leading to both catecholamines and serotonin decreases) induced the same PS deficit as in the adult cat. In the 1- and 2-week-old kittens, neither 6-OHDA alone, nor 6-OHDA with previous chlorimipramine treatment, distrubed the sleep regulations. These data are compared to similar experiments performed in the adult cat. They are discussed in terms of sleep control ontogenesis. It is concluded that the catecholaminergic system plays no important role in the mechanisms of sleep regulation in the early postnatal period in the kitten, whereas its regulatory influence on PS is confirmed in the juvenile animal. The functional maturation of the catecholaminergic system in terms of sleep regulation is achieved between the third and the fifth week of postnatal life."}
{"id": "PMID:217487", "title": "Pharmacological distinction between the excitatory junctional potential and the glutamate potential revealed by concanavalin A at the crayfish neuromuscular junction.", "content": "The effect of concanavalin A(Con A) on desensitization of the glutamate receptor was investigated in the crayfish opener muscle. The depolarization of the crayfish muscle fiber caused by bath-applied L-glutamate was greatly augmented by Con A. The time course of the appearance of the augmentation was slow. Con A completely prevented the development of desensitization of the glutamate receptor. When L-glutamate was applied iontophoretically with a constant current pulse, a decline of the depolarization was seen during the course of the drug application which was presumably due to desensitization of the glutamate receptor. The glutamate potential was slightly increased by Con A, though the increase was transient. On the other hand, the amplitude of excitatory junctional potentials (EJPs) was not increased but decreased by addition of Con A. In normal saline, the amplitudes of both glutamate potentials and EJPs remarkably decreased because of desensitization of the glutamate receptor, but the decrease in amplitude of the glutamate potential was completely prevented by previous application of Con A. On the other hand, Con A had no influence upon the decrease in amplitude of EJPs. These results show that there is a pharmacological difference between the glutamate potential and EJPs.", "contents": "Pharmacological distinction between the excitatory junctional potential and the glutamate potential revealed by concanavalin A at the crayfish neuromuscular junction. The effect of concanavalin A(Con A) on desensitization of the glutamate receptor was investigated in the crayfish opener muscle. The depolarization of the crayfish muscle fiber caused by bath-applied L-glutamate was greatly augmented by Con A. The time course of the appearance of the augmentation was slow. Con A completely prevented the development of desensitization of the glutamate receptor. When L-glutamate was applied iontophoretically with a constant current pulse, a decline of the depolarization was seen during the course of the drug application which was presumably due to desensitization of the glutamate receptor. The glutamate potential was slightly increased by Con A, though the increase was transient. On the other hand, the amplitude of excitatory junctional potentials (EJPs) was not increased but decreased by addition of Con A. In normal saline, the amplitudes of both glutamate potentials and EJPs remarkably decreased because of desensitization of the glutamate receptor, but the decrease in amplitude of the glutamate potential was completely prevented by previous application of Con A. On the other hand, Con A had no influence upon the decrease in amplitude of EJPs. These results show that there is a pharmacological difference between the glutamate potential and EJPs."}
{"id": "PMID:217492", "title": "Effects of age on brain oxidative metabolism in vivo.", "content": "Non-invasive optical techniques were used to monitor the effects of increasing cerebral energy demand on metabolic capabilities and vascular reactivity in young and aged brain. Low level of electrical stimulation of the cortex, in both young (4--7 months) and aged (24--28 months) rat brain, were accompanied by transient oxidations of NADH and cytochrome oxidase (a,a3) as measured by microfluorometry and reflection spectrophotometry respectively. Stimulation sufficient to produce spreading cortical depression was accompanied by an oxidation of both NADH and cytochrome a,a3 in young brain together with an increase in local blood volume. There was either no change or a slight disoxygenation of hemoglobin. In aged brain, however, spreading depression was associated with an oxidation of NADH and a reduction of cytochrome a,a3 together with an increase in local blood volume and an oxygenation of hemoglobin. The present results indicate that the relationship between microcirculation and the terminal oxidase step of the respiratory chain is altered in aged brain when energy demand is high.", "contents": "Effects of age on brain oxidative metabolism in vivo. Non-invasive optical techniques were used to monitor the effects of increasing cerebral energy demand on metabolic capabilities and vascular reactivity in young and aged brain. Low level of electrical stimulation of the cortex, in both young (4--7 months) and aged (24--28 months) rat brain, were accompanied by transient oxidations of NADH and cytochrome oxidase (a,a3) as measured by microfluorometry and reflection spectrophotometry respectively. Stimulation sufficient to produce spreading cortical depression was accompanied by an oxidation of both NADH and cytochrome a,a3 in young brain together with an increase in local blood volume. There was either no change or a slight disoxygenation of hemoglobin. In aged brain, however, spreading depression was associated with an oxidation of NADH and a reduction of cytochrome a,a3 together with an increase in local blood volume and an oxygenation of hemoglobin. The present results indicate that the relationship between microcirculation and the terminal oxidase step of the respiratory chain is altered in aged brain when energy demand is high."}
{"id": "PMID:217493", "title": "Developmental alteration of rat brain synaptic membranes. Reaction of glycoproteins with plant lectins.", "content": "Synaptic membranes were isolated from the forebrains of rats of increasing postnatal ages. Developmentally related changes in the structure and concnetration of synaptic membrane glycoproteins were indicated by: (1) a 2--3 fold increase in glycoprotein sialic acid between 5 and 60 days; (2) a similar increase in the number of membrane receptors for the lectins concanavalin A and wheat germ agglutinin; (3) transient increases between 10 and 17 days in the receptors for lentil and castor bean lectins and (4) an age dependent stimulation of castor bean lectin binding by neuraminidase. Labelling of SDS polysacrylamide gels of synaptic membranes with [125I]concanavalin A or wheat germ agglutinin revealed specific, age dependent changes in the lectin binding properties of individual molecular weight classes of glycoproteins. Differences in the glycoproteins composition of synaptic junctional complexes isolated from 10 and 28-day-old brains were also revealed by lectin binding studies. The results indicate that the number and structure of oligosaccharides associated with synaptic membrane glycoproteins are under developmental regulation.", "contents": "Developmental alteration of rat brain synaptic membranes. Reaction of glycoproteins with plant lectins. Synaptic membranes were isolated from the forebrains of rats of increasing postnatal ages. Developmentally related changes in the structure and concnetration of synaptic membrane glycoproteins were indicated by: (1) a 2--3 fold increase in glycoprotein sialic acid between 5 and 60 days; (2) a similar increase in the number of membrane receptors for the lectins concanavalin A and wheat germ agglutinin; (3) transient increases between 10 and 17 days in the receptors for lentil and castor bean lectins and (4) an age dependent stimulation of castor bean lectin binding by neuraminidase. Labelling of SDS polysacrylamide gels of synaptic membranes with [125I]concanavalin A or wheat germ agglutinin revealed specific, age dependent changes in the lectin binding properties of individual molecular weight classes of glycoproteins. Differences in the glycoproteins composition of synaptic junctional complexes isolated from 10 and 28-day-old brains were also revealed by lectin binding studies. The results indicate that the number and structure of oligosaccharides associated with synaptic membrane glycoproteins are under developmental regulation."}
{"id": "PMID:217494", "title": "Pharmacological and immunological characterization of the Leu5 analogue of human beta-endorphin.", "content": "The potencies of beta h-endorphin, Met (O)5-beta h-endorphin, and synthetic Leu5-beta h-endorphin have been compared in three bioassays of opioid activity, and in two radioimmunoassays. In all assays, a peptide isolated from hemodialysates from a psychotic patient behaved like Leu5-beta h-endorphin; it has been distinguished unambiguously from beta h-endorphin and Met(O)5-beta h-endorphin. Leu5-beta h-endorphin was one-fifth as potent as beta h-endorphin in guinea pig ileum myenteric plexus, but was only slightly less active in mouse vas deferens and in guinea pig brain opiate receptor binding assay. The low cross-reactivity of Leu5-beta h-endorphin relative to beta h-endorphin with an antiserum raised to beta-endorphin suggests that the preferred solution conformations of these peptides are different. In all bioassays beta h-endorphin was 2- to 3-fold less potent than beta c-endorphin.", "contents": "Pharmacological and immunological characterization of the Leu5 analogue of human beta-endorphin. The potencies of beta h-endorphin, Met (O)5-beta h-endorphin, and synthetic Leu5-beta h-endorphin have been compared in three bioassays of opioid activity, and in two radioimmunoassays. In all assays, a peptide isolated from hemodialysates from a psychotic patient behaved like Leu5-beta h-endorphin; it has been distinguished unambiguously from beta h-endorphin and Met(O)5-beta h-endorphin. Leu5-beta h-endorphin was one-fifth as potent as beta h-endorphin in guinea pig ileum myenteric plexus, but was only slightly less active in mouse vas deferens and in guinea pig brain opiate receptor binding assay. The low cross-reactivity of Leu5-beta h-endorphin relative to beta h-endorphin with an antiserum raised to beta-endorphin suggests that the preferred solution conformations of these peptides are different. In all bioassays beta h-endorphin was 2- to 3-fold less potent than beta c-endorphin."}
{"id": "PMID:217496", "title": "Effect of cyclic nucleotides on high affinity uptake of L-glutamate and taurine in glial and neuroblastoma cells.", "content": "Cultured glial cells (clones NN and I6) and neuroblastoma cells (clones M1 and M1NN) were used to study the effect of cyclic nucleotides on high affinity uptake of L-glutamate and taurine. Treatment of NN cells with a mixture of dBcAMP and BrcGMP for one or two days resulted in a more than 3-fold increase in the Vmax of L-glutamate high affinity uptake. Similar but smaller change was observed in a related glial clone (I6). Effects of cyclic nucleotide derivatives on high affinity uptake of L-glutamate by neuroblastoma cells (clones M1 and M1NN) or of taurine by both glial or neuroblastoma cells were either smaller or absent. Some differences were found in kinetic parameters of uptake of L-glutamate and taurine by original and re-isolated cellls, respectively. It is possible that these differences resulted from co-cultivation of glial and neuronal cells. However, since some values reported in this paper differ to some extent from those published previously, some other factors, such as subcloning, may have been responsible.", "contents": "Effect of cyclic nucleotides on high affinity uptake of L-glutamate and taurine in glial and neuroblastoma cells. Cultured glial cells (clones NN and I6) and neuroblastoma cells (clones M1 and M1NN) were used to study the effect of cyclic nucleotides on high affinity uptake of L-glutamate and taurine. Treatment of NN cells with a mixture of dBcAMP and BrcGMP for one or two days resulted in a more than 3-fold increase in the Vmax of L-glutamate high affinity uptake. Similar but smaller change was observed in a related glial clone (I6). Effects of cyclic nucleotide derivatives on high affinity uptake of L-glutamate by neuroblastoma cells (clones M1 and M1NN) or of taurine by both glial or neuroblastoma cells were either smaller or absent. Some differences were found in kinetic parameters of uptake of L-glutamate and taurine by original and re-isolated cellls, respectively. It is possible that these differences resulted from co-cultivation of glial and neuronal cells. However, since some values reported in this paper differ to some extent from those published previously, some other factors, such as subcloning, may have been responsible."}
{"id": "PMID:217497", "title": "Depolarization-induced decreases in fluroescence intensity of gastro-intestinal quinacrine-binding nerves.", "content": "Quinacrine, a fluorescent antimalarial acridine derivative, selectively binds to a population of nerve cell bodies and nerve fibers in Auerbach's plexus and elsewhere in the gut. This quinacrine-binding, as measured by fluorescence intensity, is reduced if the nervous elements are depolarized by high K+ (80--150 MM) or veratridine (5 x 10(-5) M) during quinacrine incubation. A reduction of quinacrine-content in nerve terminals is also seen when depolarization (veratridine) takes place for 2 min after quinacrine-incubation, indicating a release of already bound quinacrine. If terminals are depolarized (high K+ or veratridine) before quinacrine incubation, a reduction of quinacrine content is also seen. The depolarization-induced reduction of quinacrine-binding is blocked by Ca2+-removal and, in the case of veratridine by tetrodotoxin. Our findings suggest that quinacrine binds to a compound that is released by nervous activity. Binding mechanism remains to be elucidated. The possibility that quinacrine visualized purine-rich structures is discussed.", "contents": "Depolarization-induced decreases in fluroescence intensity of gastro-intestinal quinacrine-binding nerves. Quinacrine, a fluorescent antimalarial acridine derivative, selectively binds to a population of nerve cell bodies and nerve fibers in Auerbach's plexus and elsewhere in the gut. This quinacrine-binding, as measured by fluorescence intensity, is reduced if the nervous elements are depolarized by high K+ (80--150 MM) or veratridine (5 x 10(-5) M) during quinacrine incubation. A reduction of quinacrine-content in nerve terminals is also seen when depolarization (veratridine) takes place for 2 min after quinacrine-incubation, indicating a release of already bound quinacrine. If terminals are depolarized (high K+ or veratridine) before quinacrine incubation, a reduction of quinacrine content is also seen. The depolarization-induced reduction of quinacrine-binding is blocked by Ca2+-removal and, in the case of veratridine by tetrodotoxin. Our findings suggest that quinacrine binds to a compound that is released by nervous activity. Binding mechanism remains to be elucidated. The possibility that quinacrine visualized purine-rich structures is discussed."}
{"id": "PMID:217502", "title": "Taurine: stimulation of pineal N-acetyltransferase activity and melatonin production via a beta-adrenergic mechanism.", "content": "Pineal glands convert [3H]tryptophan to [3H]N-acetylserotonin and [3H]melatonin in organ culture. Taurine treatment increases the rate of production of these compounds 40- and 25-fold respectively by stimulating the activity of N-acetyltransferase. This stimulation is blocked stereospecifically by L-propranolol, indicating that taurine is probably acting via beta-adrenergic receptors. Taurine is active in stimulating N-acetyltransferase activity in denervated glands, suggesting that it might interact directly with the beta-adrenergic receptor, and not by causing the release of norepinephrine from nerve terminals.", "contents": "Taurine: stimulation of pineal N-acetyltransferase activity and melatonin production via a beta-adrenergic mechanism. Pineal glands convert [3H]tryptophan to [3H]N-acetylserotonin and [3H]melatonin in organ culture. Taurine treatment increases the rate of production of these compounds 40- and 25-fold respectively by stimulating the activity of N-acetyltransferase. This stimulation is blocked stereospecifically by L-propranolol, indicating that taurine is probably acting via beta-adrenergic receptors. Taurine is active in stimulating N-acetyltransferase activity in denervated glands, suggesting that it might interact directly with the beta-adrenergic receptor, and not by causing the release of norepinephrine from nerve terminals."}
{"id": "PMID:217503", "title": "Immunohistochemical mapping of enkephalin containing cell bodies, fibers and nerve terminals in the brain stem of the rat.", "content": "Enkephalin immunoreactive perikarya, fibers and nerve terminals, visualized by the indirect immunohistofluorescent method in colchicine-pretreated animals, are localized in many discrete regions of the rat brain stem. These specific immunohistofluorescent patterns are similar after staining with selective primary antisera directed against either methionine-enkephalin or leucine-enkephalin. Cell bodies are found in the substantia gelatinosa and interpolaris zones of the trigeminal nuclear complex, the nucleus of the solitary tract, in the vicinity of the nucleus raph\u00e9 magnus, in the dorsal cochlear, medial vestibular, and paraolivary nuclei and, dorsal to this last region, in the parabrachial nuclei and the dorsal tegmental nucleus of Gudden, in the periaqueductal gray matter and interpeduncular nucleus and along the borders of the lateral lemniscus and medial geniculate. In some areas, such as the parabrachial region, nucleus of the solitary tract and substantia gelatinosa of the trigeminal nucleus, these perikarya are associated with densities of fibers and terminals. Other regions, such as the dorsal cochlear nucleus and the vicinity of the nucleus raph\u00e9 magnus, contain cell bodies associated with low densities of processes and terminals. In still other nuclei, such as the nucleus of the facial nerve and the locus coeruleus, fiber and terminal densities without associated cell bodies are evident. Many of these enkephalin localizations can be rationalized on the basis of known actions of opiate drugs and the brain stem distribution of opiate receptors.", "contents": "Immunohistochemical mapping of enkephalin containing cell bodies, fibers and nerve terminals in the brain stem of the rat. Enkephalin immunoreactive perikarya, fibers and nerve terminals, visualized by the indirect immunohistofluorescent method in colchicine-pretreated animals, are localized in many discrete regions of the rat brain stem. These specific immunohistofluorescent patterns are similar after staining with selective primary antisera directed against either methionine-enkephalin or leucine-enkephalin. Cell bodies are found in the substantia gelatinosa and interpolaris zones of the trigeminal nuclear complex, the nucleus of the solitary tract, in the vicinity of the nucleus raph\u00e9 magnus, in the dorsal cochlear, medial vestibular, and paraolivary nuclei and, dorsal to this last region, in the parabrachial nuclei and the dorsal tegmental nucleus of Gudden, in the periaqueductal gray matter and interpeduncular nucleus and along the borders of the lateral lemniscus and medial geniculate. In some areas, such as the parabrachial region, nucleus of the solitary tract and substantia gelatinosa of the trigeminal nucleus, these perikarya are associated with densities of fibers and terminals. Other regions, such as the dorsal cochlear nucleus and the vicinity of the nucleus raph\u00e9 magnus, contain cell bodies associated with low densities of processes and terminals. In still other nuclei, such as the nucleus of the facial nerve and the locus coeruleus, fiber and terminal densities without associated cell bodies are evident. Many of these enkephalin localizations can be rationalized on the basis of known actions of opiate drugs and the brain stem distribution of opiate receptors."}
{"id": "PMID:217504", "title": "The postulated role of feeder swine in the perpetuation of the transmissible gastroenteritis virus.", "content": "Clinical, immunofluorescence and histopathological observations were found to be an efficient approach for the confirmation of the diagnosis of transmissible gastroenteritis in feeder swine. Two cases are reported to exemplify how feeder swine exposed to points of concentration such as holding areas, sales barns and auctions can play an important role in the epizootiology of transmissible gastroenteritis. A third field case is reported as an example of an outbreak of transmissible gastroenteritis beginning in feeder swine and then spreading to baby pigs on the farm. All baby pigs died that were born during the acute phase of the outbreak in the feeder swine. Baby pigs born shortly after the clinical signs had abated in the herd, and from sows that had been exposed orally to virulent transmissible gastroenteritis virus and vaccinated with a commercial transmissible gastroenteritis vaccine ten days before farrowing, survived. This was explained by a combination of a decrease in the amount of virus shed in the environment and the immunity induced in the sows. These observations of field outbreaks of transmissible gastroenteritis combined with recently reported experimental studies lend strong support to the hypothesis of a reservoir for transmissible gastroenteritis virus in feeder pigs. This reservoir would be based principally on the transmission of the virus on a continuous basis from the feces of recently infected pigs to susceptible pigs. Clinical signs of transmissible gastroenteritis in such pigs are difficult to recognize or absent and this contributes to the importance of the reservoir in the field.", "contents": "The postulated role of feeder swine in the perpetuation of the transmissible gastroenteritis virus. Clinical, immunofluorescence and histopathological observations were found to be an efficient approach for the confirmation of the diagnosis of transmissible gastroenteritis in feeder swine. Two cases are reported to exemplify how feeder swine exposed to points of concentration such as holding areas, sales barns and auctions can play an important role in the epizootiology of transmissible gastroenteritis. A third field case is reported as an example of an outbreak of transmissible gastroenteritis beginning in feeder swine and then spreading to baby pigs on the farm. All baby pigs died that were born during the acute phase of the outbreak in the feeder swine. Baby pigs born shortly after the clinical signs had abated in the herd, and from sows that had been exposed orally to virulent transmissible gastroenteritis virus and vaccinated with a commercial transmissible gastroenteritis vaccine ten days before farrowing, survived. This was explained by a combination of a decrease in the amount of virus shed in the environment and the immunity induced in the sows. These observations of field outbreaks of transmissible gastroenteritis combined with recently reported experimental studies lend strong support to the hypothesis of a reservoir for transmissible gastroenteritis virus in feeder pigs. This reservoir would be based principally on the transmission of the virus on a continuous basis from the feces of recently infected pigs to susceptible pigs. Clinical signs of transmissible gastroenteritis in such pigs are difficult to recognize or absent and this contributes to the importance of the reservoir in the field."}
{"id": "PMID:217505", "title": "The use of immunofluorescence techniques for the laboratory diagnosis of transmissible gastroenteritis of swine.", "content": "Over a four year period, 74 of 250 field outbreaks of enteric disease (30%) and 110 of 440 swine (25%) were positive for transmissible gastroenteritis by immunofluorescence procedures. Of 141 swine from herds positive for transmissible gastroenteritis 110 (78%) were positive by fluorescent antibody techniques. The fastest, easiest to perform and most effective procedure was the examination of frozen sections of the jejunum from acutely ill animals by the fluorescent antibody tissue section technique. Only two herds were found to be positive by the fluorescent antibody tissue culture technique which were negative by fluorescent antibody tissue section technique. A considerable number of outbreaks, 21 of 74 (28%), of transmissible gastroenteritis were detected by immunofluorescence in swine over two weeks of age. The majority of outbreaks of transmissible gastroenteritis, 50 of 74 (68%), occurred in Missouri during the months of January through April and 63 of 74 (85%) during the months of December through May. The recurrence of the disease in a number of counties over a four-year period suggest the possibility of endemic foci.", "contents": "The use of immunofluorescence techniques for the laboratory diagnosis of transmissible gastroenteritis of swine. Over a four year period, 74 of 250 field outbreaks of enteric disease (30%) and 110 of 440 swine (25%) were positive for transmissible gastroenteritis by immunofluorescence procedures. Of 141 swine from herds positive for transmissible gastroenteritis 110 (78%) were positive by fluorescent antibody techniques. The fastest, easiest to perform and most effective procedure was the examination of frozen sections of the jejunum from acutely ill animals by the fluorescent antibody tissue section technique. Only two herds were found to be positive by the fluorescent antibody tissue culture technique which were negative by fluorescent antibody tissue section technique. A considerable number of outbreaks, 21 of 74 (28%), of transmissible gastroenteritis were detected by immunofluorescence in swine over two weeks of age. The majority of outbreaks of transmissible gastroenteritis, 50 of 74 (68%), occurred in Missouri during the months of January through April and 63 of 74 (85%) during the months of December through May. The recurrence of the disease in a number of counties over a four-year period suggest the possibility of endemic foci."}
{"id": "PMID:217506", "title": "Mechanisms of recovery from Herpesvirus infections -a review.", "content": "A variety of specific immunological mechanisms have been shown to be effective at neutralizing herpesviruses or destroying herpesvirus infected cells. These include both humoral and cell mediated immune responses or combinations thereof. Thus, it is genarlly accepted that humoral immunity is probably responsible for preventing reinfection whereas cellular immunity, mediated by T lymphocytes or by the interaction of antibody and Fc receptor bearing cells, is more important in recovery from infections. In addition to these specific responses to herpesvirus infection, a number of nonspecific cellular and humoral components have been shown to inhibit the progression of virus replication and therefore, have been implicated in assisting the host in the recovery process. The various interactions and counteractions between the various nonspecific and specific components of the immune response are discussed with respect to their role in recovery from both primary and recurrent disease as well as how they may eventually be manipulated so as to control herpesvirus recrudescent disease.", "contents": "Mechanisms of recovery from Herpesvirus infections -a review. A variety of specific immunological mechanisms have been shown to be effective at neutralizing herpesviruses or destroying herpesvirus infected cells. These include both humoral and cell mediated immune responses or combinations thereof. Thus, it is genarlly accepted that humoral immunity is probably responsible for preventing reinfection whereas cellular immunity, mediated by T lymphocytes or by the interaction of antibody and Fc receptor bearing cells, is more important in recovery from infections. In addition to these specific responses to herpesvirus infection, a number of nonspecific cellular and humoral components have been shown to inhibit the progression of virus replication and therefore, have been implicated in assisting the host in the recovery process. The various interactions and counteractions between the various nonspecific and specific components of the immune response are discussed with respect to their role in recovery from both primary and recurrent disease as well as how they may eventually be manipulated so as to control herpesvirus recrudescent disease."}
{"id": "PMID:217507", "title": "A simple, rapid syncytial-inhibition test for antibodies to bovine leukemia virus.", "content": "Cocultivation of equal numbers of cells from a fetal lamb kidney line infected with bovine leukemia virus and African green monkey (Vero) cells results in the rapid production of syncytia. The effect was blocked or inhibited by serum containing antibodies to bovine leukemia virus. A serological test based on syncytial inhibition was compared to the agar gel immunodiffusion test and the modified direct complement fixation test for the detection of bovine leukemia virus antibodies in sera from leukosis-free cattle, cases of adult enzootic bovine lymphosarcoma and cattle from herds in contact with enzootic lymphosarcoma. The results showed the syncytial inhibition test to react positively with sera from all cases of adult enzootic lymphosarcoma, but to be much less sensitive than the other tests in detecting bovine leukemia virus antibodies in sera of exposed animals.", "contents": "A simple, rapid syncytial-inhibition test for antibodies to bovine leukemia virus. Cocultivation of equal numbers of cells from a fetal lamb kidney line infected with bovine leukemia virus and African green monkey (Vero) cells results in the rapid production of syncytia. The effect was blocked or inhibited by serum containing antibodies to bovine leukemia virus. A serological test based on syncytial inhibition was compared to the agar gel immunodiffusion test and the modified direct complement fixation test for the detection of bovine leukemia virus antibodies in sera from leukosis-free cattle, cases of adult enzootic bovine lymphosarcoma and cattle from herds in contact with enzootic lymphosarcoma. The results showed the syncytial inhibition test to react positively with sera from all cases of adult enzootic lymphosarcoma, but to be much less sensitive than the other tests in detecting bovine leukemia virus antibodies in sera of exposed animals."}
{"id": "PMID:217508", "title": "Experimental intraamnionic exposure of bovine fetuses with subgroup 2, type 7 Adenovirus.", "content": "Three third trimester fetuses were exposed to a subgroup 2, type 7 adenovirus (adeno 7) by intraamnionic infection. The virus caused preterm delivery of two clinically ill calves and one stillbirth. The two premature calves died 12 and 72 hours after birth. An elevated serum neutralizing antibody titer (1:256) to adenovirus 7 was found in one principal calf at birth. Adenovirus 7 was recovered from several tissues of the live calves and the spleen of the stillborn calf. Fetuses exposed by intraamniotnic injection with virus carrier only, were born healthy after normal gestational periods and no viruses were isolated from the tissues. Clinically ill calves were weak, severely depressed and unable to stand and nurse. Gross postmortem lesions were nonspecific and consisted of petechial and ecchymotic hemorrhages and edema of the gastrointestinal tract. Histopathological lesions included vasculitis, necrosis of the mucosa of the forestomach, mild gastroenteritis and acute, nonsuppurative focal necrosis of the liver, kidney and adrenal gland. Intranuclear inclusion bodies were seen in pericytes, macrophages, hepatocytes, epithelial cells of adrenal cortical sinusoids of the zona glomerulosa and zona fasciculata and renal tubular epithelium.", "contents": "Experimental intraamnionic exposure of bovine fetuses with subgroup 2, type 7 Adenovirus. Three third trimester fetuses were exposed to a subgroup 2, type 7 adenovirus (adeno 7) by intraamnionic infection. The virus caused preterm delivery of two clinically ill calves and one stillbirth. The two premature calves died 12 and 72 hours after birth. An elevated serum neutralizing antibody titer (1:256) to adenovirus 7 was found in one principal calf at birth. Adenovirus 7 was recovered from several tissues of the live calves and the spleen of the stillborn calf. Fetuses exposed by intraamniotnic injection with virus carrier only, were born healthy after normal gestational periods and no viruses were isolated from the tissues. Clinically ill calves were weak, severely depressed and unable to stand and nurse. Gross postmortem lesions were nonspecific and consisted of petechial and ecchymotic hemorrhages and edema of the gastrointestinal tract. Histopathological lesions included vasculitis, necrosis of the mucosa of the forestomach, mild gastroenteritis and acute, nonsuppurative focal necrosis of the liver, kidney and adrenal gland. Intranuclear inclusion bodies were seen in pericytes, macrophages, hepatocytes, epithelial cells of adrenal cortical sinusoids of the zona glomerulosa and zona fasciculata and renal tubular epithelium."}
{"id": "PMID:217509", "title": "Acetaldehyde affects mammalian neuromuscular transmission without observable postsynaptic effects.", "content": "Acetaldehyde, the first metabolite of ethanol, caused a reversible block of the end-plate potential (EPP) in the rat and mouse phrenic nerve--hemidiaphragm preparation. Decrease and block of the EPP occurred over a bath concentration range from 3 to 25 mM. The phrenic nerve compound action potential was blocked along with the EPP, and this block was not reversed by high bath Ca2+ concentration. The muscle action potential was unaffected even at concentrations up to 50 mM. Over the same concentration range (3--25 mM), miniature end-plate potential (MEPP) frequency sometimes decreased a few minutes after application, and over the ensuing 10--20 min would steadily increase to as much as 11 times the base-line frequency, particularly with higher doses. However, the shape of averaged MEPPs remained unchanged after acetaldehyde application, suggesting that this aldehyde does not have post-synaptic effects.", "contents": "Acetaldehyde affects mammalian neuromuscular transmission without observable postsynaptic effects. Acetaldehyde, the first metabolite of ethanol, caused a reversible block of the end-plate potential (EPP) in the rat and mouse phrenic nerve--hemidiaphragm preparation. Decrease and block of the EPP occurred over a bath concentration range from 3 to 25 mM. The phrenic nerve compound action potential was blocked along with the EPP, and this block was not reversed by high bath Ca2+ concentration. The muscle action potential was unaffected even at concentrations up to 50 mM. Over the same concentration range (3--25 mM), miniature end-plate potential (MEPP) frequency sometimes decreased a few minutes after application, and over the ensuing 10--20 min would steadily increase to as much as 11 times the base-line frequency, particularly with higher doses. However, the shape of averaged MEPPs remained unchanged after acetaldehyde application, suggesting that this aldehyde does not have post-synaptic effects."}
{"id": "PMID:217510", "title": "Characterization of the inotropic response induced by stimulation of beta-adrenergic and H1 histaminergic receptors in guinea pig left atria.", "content": "The inotropic response induced by beta-adrenergic and H1 histaminergic receptor stimulation was characterized in guinea pig left atria by obtaining dose-response relationships for isoproterenol and histamine under various experimental conditions. Conditions (hypothermia, high frequencies of stimulation, and large extracellular calcium concentrations) which enhanced the ability of cardiac muscle to develop force also increased the sensitivity of the left atrium to isoproterenol while decreasing its efficacy. On the other hand, conditions which enhanced the ability of cardiac muscle to develop force depressed the efficacy of histamine to such an extent that the sensitivity to histamine was also decreased. In addition, conditions which markedly depressed the ability of cardiac muscle to develop force also decreased the efficacy and sensitivity to histamine. The data indicate that while beta-adrenoceptor stimulation results in an inotropic response under all conditions studied, stimulation of H1 histaminergic receptors results in an inotropic response only within a narrow range of experimental conditions.", "contents": "Characterization of the inotropic response induced by stimulation of beta-adrenergic and H1 histaminergic receptors in guinea pig left atria. The inotropic response induced by beta-adrenergic and H1 histaminergic receptor stimulation was characterized in guinea pig left atria by obtaining dose-response relationships for isoproterenol and histamine under various experimental conditions. Conditions (hypothermia, high frequencies of stimulation, and large extracellular calcium concentrations) which enhanced the ability of cardiac muscle to develop force also increased the sensitivity of the left atrium to isoproterenol while decreasing its efficacy. On the other hand, conditions which enhanced the ability of cardiac muscle to develop force depressed the efficacy of histamine to such an extent that the sensitivity to histamine was also decreased. In addition, conditions which markedly depressed the ability of cardiac muscle to develop force also decreased the efficacy and sensitivity to histamine. The data indicate that while beta-adrenoceptor stimulation results in an inotropic response under all conditions studied, stimulation of H1 histaminergic receptors results in an inotropic response only within a narrow range of experimental conditions."}
{"id": "PMID:217511", "title": "Photoaffinity labeling of the angiotensin II receptor; pharmacology of the labeling peptides in the dark.", "content": "The biological activities of photoaffinity labeling analogs of angiotensin II (ATII) and their precursors were measured in rabbit aorta strips in the dark. Most of the analogs behave as reversible, specific agonists, one as a competitive inhibitor. The activities are discussed in line with the current view of structural requirements. The modifications consisted of substitutions on the aromatic nuclei of Tyr4 and Phe8 in [Sar1]ATII with (4'-NO2) Phe, (4'-NH2)Phe, (4'N3)Phe, (4'-N2 +)Phe, and (4'-NH2-3', 5'-I2)Phe. It is shown that the affinity of the ATII analogs modified in position 4 depends on the electronegativity and not on space-filling properties of the aromatic residue; rising electronegativity lowers the affinity, i.e. [sar1, (4'-NO2)Phe4]ATII has no more measurable activity. Substituting the aromatic side chain in position 8 of [Sar1]ATII gives well-binding analogs with intrinsic activities from 0 to 100% and activity seems to depend only on stereochemical requirements. Agonists and partial agonists bear rather small groups like -NH2, -N3, -NO2, and -N2 +. The only antagonist [Sar1, (4'-NH2-3',5'-I2)Phe8]ATII resembles the antagonist E1Sar1, Leu8]ATII in competitivity and binding.", "contents": "Photoaffinity labeling of the angiotensin II receptor; pharmacology of the labeling peptides in the dark. The biological activities of photoaffinity labeling analogs of angiotensin II (ATII) and their precursors were measured in rabbit aorta strips in the dark. Most of the analogs behave as reversible, specific agonists, one as a competitive inhibitor. The activities are discussed in line with the current view of structural requirements. The modifications consisted of substitutions on the aromatic nuclei of Tyr4 and Phe8 in [Sar1]ATII with (4'-NO2) Phe, (4'-NH2)Phe, (4'N3)Phe, (4'-N2 +)Phe, and (4'-NH2-3', 5'-I2)Phe. It is shown that the affinity of the ATII analogs modified in position 4 depends on the electronegativity and not on space-filling properties of the aromatic residue; rising electronegativity lowers the affinity, i.e. [sar1, (4'-NO2)Phe4]ATII has no more measurable activity. Substituting the aromatic side chain in position 8 of [Sar1]ATII gives well-binding analogs with intrinsic activities from 0 to 100% and activity seems to depend only on stereochemical requirements. Agonists and partial agonists bear rather small groups like -NH2, -N3, -NO2, and -N2 +. The only antagonist [Sar1, (4'-NH2-3',5'-I2)Phe8]ATII resembles the antagonist E1Sar1, Leu8]ATII in competitivity and binding."}
{"id": "PMID:217512", "title": "Stereospecific presynaptic inhibitory effect of delta9-tetrahydrocannabinol on cholinergic transmission in the myenteric plexus of the guinea pig.", "content": "delta9-Tetrahydrocannabinol (THC) is very lipid soluble, as are many anesthetic agents. The action of anesthetics is nonspecific; isomers are equieffective. THC is optically active; therefore, the effects of its stereoisomers were studied on the electrically and chemically stimulated longitudinal muscle strip of guinea pig ileum. The results demonstrate that both isomers depress the response to electrical stimulation in a dose-related manner. The maximum effect is gradually reached in approximately 20 min. The (-) isomer is 24.6-fold more active than the (+) isomer (ED50 for (-) THC is 1.25 X 10(-7) M, for (+) THC, 3.08 X 10(-6) M) and the site of action appears to be presynaptic because responses to ACh are not significantly depressed. The depressant effects are relatively nonreversible. Membrane concentrations calculated at the ED50 values for the (-) isomer are of the order of 0.5 mM/kg dry membrane, well within the range for anesthesia. Thus THC may be regarded as a partial anesthetic since some of its actions are similar to those of the classical anesthetics, yet it possesses selective action at the neuronal membrane or tissue level.", "contents": "Stereospecific presynaptic inhibitory effect of delta9-tetrahydrocannabinol on cholinergic transmission in the myenteric plexus of the guinea pig. delta9-Tetrahydrocannabinol (THC) is very lipid soluble, as are many anesthetic agents. The action of anesthetics is nonspecific; isomers are equieffective. THC is optically active; therefore, the effects of its stereoisomers were studied on the electrically and chemically stimulated longitudinal muscle strip of guinea pig ileum. The results demonstrate that both isomers depress the response to electrical stimulation in a dose-related manner. The maximum effect is gradually reached in approximately 20 min. The (-) isomer is 24.6-fold more active than the (+) isomer (ED50 for (-) THC is 1.25 X 10(-7) M, for (+) THC, 3.08 X 10(-6) M) and the site of action appears to be presynaptic because responses to ACh are not significantly depressed. The depressant effects are relatively nonreversible. Membrane concentrations calculated at the ED50 values for the (-) isomer are of the order of 0.5 mM/kg dry membrane, well within the range for anesthesia. Thus THC may be regarded as a partial anesthetic since some of its actions are similar to those of the classical anesthetics, yet it possesses selective action at the neuronal membrane or tissue level."}
{"id": "PMID:217513", "title": "Effect of ovine prolactin on serum somatomedin bioactivity in hypophysectomized female rats.", "content": "Ovine prolactin (oPRL) increased serum somatomedin (SM) bioactivity in hypophysectomized female rats. ACTH, in small but not large doses, augmented this oPRL effect. These results suggest that in the female rat PRL may regulate SM production. Adrenal factors may variably modulate SM production or serum SM bioactivity.", "contents": "Effect of ovine prolactin on serum somatomedin bioactivity in hypophysectomized female rats. Ovine prolactin (oPRL) increased serum somatomedin (SM) bioactivity in hypophysectomized female rats. ACTH, in small but not large doses, augmented this oPRL effect. These results suggest that in the female rat PRL may regulate SM production. Adrenal factors may variably modulate SM production or serum SM bioactivity."}
{"id": "PMID:217514", "title": "5-Fluoroorotate-resistant mutants of Salmonella typhimurium.", "content": "Spontaneously occurring mutants of Salmonella typhimurium resistant to 5-fluoroorotate (5-FOA) were isolated. One class of mutant showed marked derepression of pyrimidine biosynthetic enzymes and had the unusual property of being unable to grow on nutrient agar. However, when the osmotic strength of nutrient agar was increased, the mutants were able to grow. The genetic basis for the osmotic fragility and elevated pyr enzyme synthesis was the result of mutations affecting pyrH, encoding the enzyme uridine 5'-monophosphate kinase.", "contents": "5-Fluoroorotate-resistant mutants of Salmonella typhimurium. Spontaneously occurring mutants of Salmonella typhimurium resistant to 5-fluoroorotate (5-FOA) were isolated. One class of mutant showed marked derepression of pyrimidine biosynthetic enzymes and had the unusual property of being unable to grow on nutrient agar. However, when the osmotic strength of nutrient agar was increased, the mutants were able to grow. The genetic basis for the osmotic fragility and elevated pyr enzyme synthesis was the result of mutations affecting pyrH, encoding the enzyme uridine 5'-monophosphate kinase."}
{"id": "PMID:217515", "title": "Construction of an Escherichia coli strain which excretes abnormally large amounts of adenosine 3',5'-cyclic monophosphate.", "content": "It has previously been shown that an Escherichia coli CRP- strain 5333 accumulates abnormally large amounts of adenosine 3',5'-cyclic monophosphate (cAMP). Using P1 transduction, the CRP- character was transferred to E. coli Crookes strain which is deficient for cAMP phophodiesterase (CPD-). The resulting strain HY22 (CRP-, CPD-) accumulates greater amounts of cAMP both intracellularly and extracellularly than does 5333. In glucose minimal medium, an HY22 cell accumulates 100 times more cAMP intracellularly and excretes cAMP 150 times faster than does a wild-type E. coli cell.", "contents": "Construction of an Escherichia coli strain which excretes abnormally large amounts of adenosine 3',5'-cyclic monophosphate. It has previously been shown that an Escherichia coli CRP- strain 5333 accumulates abnormally large amounts of adenosine 3',5'-cyclic monophosphate (cAMP). Using P1 transduction, the CRP- character was transferred to E. coli Crookes strain which is deficient for cAMP phophodiesterase (CPD-). The resulting strain HY22 (CRP-, CPD-) accumulates greater amounts of cAMP both intracellularly and extracellularly than does 5333. In glucose minimal medium, an HY22 cell accumulates 100 times more cAMP intracellularly and excretes cAMP 150 times faster than does a wild-type E. coli cell."}
{"id": "PMID:217516", "title": "Automatic quantitative analysis of the electromyogram in partially denervated distal muscles: comparison with motor unit counting.", "content": "Using the ANOPS-101 minicomputer, an automatic analysis of muscle action potentials (MAP) was performed on a total of 53 extensor digitorum brevis (EDB) and abductor pollicis brevis (APB) muscles in patients with other evidence of denervation. The results were compared with observations made on 27 control subjects and they were also matched against estimates of functioning motor units made by the incremental stimulating technique of McComas et al (1971). Although the incidence of abnormal MAP parameters was relatively low in both muscles, it was possible to improve the diagnostic yield by combining the results for individual muscles. The relative merits and disadvantages of motor unit counting and automatic MAP analysis are discussed.", "contents": "Automatic quantitative analysis of the electromyogram in partially denervated distal muscles: comparison with motor unit counting. Using the ANOPS-101 minicomputer, an automatic analysis of muscle action potentials (MAP) was performed on a total of 53 extensor digitorum brevis (EDB) and abductor pollicis brevis (APB) muscles in patients with other evidence of denervation. The results were compared with observations made on 27 control subjects and they were also matched against estimates of functioning motor units made by the incremental stimulating technique of McComas et al (1971). Although the incidence of abnormal MAP parameters was relatively low in both muscles, it was possible to improve the diagnostic yield by combining the results for individual muscles. The relative merits and disadvantages of motor unit counting and automatic MAP analysis are discussed."}
{"id": "PMID:217517", "title": "Accumulation and removal of Hg203 in different regions of the rat brain.", "content": "We have studied the brain regional distribution of methyl mercury following intravenous administration of CH3 203HgCl in rat. Early peak levels were obtained in cerebellum, medulla oblongata and midbrain. The efficacy of removal of 203Hg by different chelators is also region dependent. The most efficient chelator for brain mercury proved to be mesodimercaptosuccinic acid.", "contents": "Accumulation and removal of Hg203 in different regions of the rat brain. We have studied the brain regional distribution of methyl mercury following intravenous administration of CH3 203HgCl in rat. Early peak levels were obtained in cerebellum, medulla oblongata and midbrain. The efficacy of removal of 203Hg by different chelators is also region dependent. The most efficient chelator for brain mercury proved to be mesodimercaptosuccinic acid."}
{"id": "PMID:217518", "title": "Virology and histopathology of the trigeminal ganglia of Americans and Japanese.", "content": "Herpes simplex virus in the trigeminal ganglia of humans was studied in Philadelphia, Pennsylvania, United States of America, and in Kyoto, Japan. The prevalence of recurrent herpes labialis and of clinically latent herpes simplex virus within trigeminal ganglia was determined in inhabitants of the two cities. In addition, a comparison was made of the prevalence of mononuclear cell infiltration in the trigeminal ganglia of Americans and Japanese. Recurrent herpes labialis was found to be significantly less common in the Japanese city than in the American city. Herpes simplex virus was rescued less commonly from the trigeminal ganglia of cadavers in Japan than in America. The difference was significant. The frequency of mononuclear cell infiltration in the trigeminal ganglia of Americans and Japanese is not significantly different. These observations, as well as previously reported serological studies, suggest that despite the ubiquitous nature of herpes simplex virus in America and Japan, the Japanese have less clinically overt disease caused by this virus.", "contents": "Virology and histopathology of the trigeminal ganglia of Americans and Japanese. Herpes simplex virus in the trigeminal ganglia of humans was studied in Philadelphia, Pennsylvania, United States of America, and in Kyoto, Japan. The prevalence of recurrent herpes labialis and of clinically latent herpes simplex virus within trigeminal ganglia was determined in inhabitants of the two cities. In addition, a comparison was made of the prevalence of mononuclear cell infiltration in the trigeminal ganglia of Americans and Japanese. Recurrent herpes labialis was found to be significantly less common in the Japanese city than in the American city. Herpes simplex virus was rescued less commonly from the trigeminal ganglia of cadavers in Japan than in America. The difference was significant. The frequency of mononuclear cell infiltration in the trigeminal ganglia of Americans and Japanese is not significantly different. These observations, as well as previously reported serological studies, suggest that despite the ubiquitous nature of herpes simplex virus in America and Japan, the Japanese have less clinically overt disease caused by this virus."}
{"id": "PMID:217519", "title": "Anabolic steroid therapy and intrahepatic cholangiocarcinoma.", "content": "A 47-year-old man who had been treated with an anabolic steroid for refractory anemia developed an intrahepatic cholangiocarcinoma with metastases to abdominal lymph nodes and lungs. Microscopically, the tumor showed mucin production and was devoid of hepatocellular elements. Previous reports have suggested a possible relationship between anabolic steroid therapy and hepatocellular carcinoma. In many such cases, there are doubts about the histological diagnosis, malignant potential, and the nature of the association between the steroids and the tumors. The presence of distant metastases attests to the malignant nature of the tumor in the present case. Despite the apparent temporal eligibility of the steroid as an etiologic agent, a causative relationship between therapy and tumor is not established.", "contents": "Anabolic steroid therapy and intrahepatic cholangiocarcinoma. A 47-year-old man who had been treated with an anabolic steroid for refractory anemia developed an intrahepatic cholangiocarcinoma with metastases to abdominal lymph nodes and lungs. Microscopically, the tumor showed mucin production and was devoid of hepatocellular elements. Previous reports have suggested a possible relationship between anabolic steroid therapy and hepatocellular carcinoma. In many such cases, there are doubts about the histological diagnosis, malignant potential, and the nature of the association between the steroids and the tumors. The presence of distant metastases attests to the malignant nature of the tumor in the present case. Despite the apparent temporal eligibility of the steroid as an etiologic agent, a causative relationship between therapy and tumor is not established."}
{"id": "PMID:217520", "title": "Severe pulmonary hemorrhage following lymphography.", "content": "The hemoptysis which occurs following lymphography typically consists of one or more episodes of blood-tinged sputum, and generally requires no treatment. In contradistinction to this \"mild\" form of hemoptysis, the current report describes a case of hemoptysis following lymphography--hemoptysis so severe as to require multiple transfusions. Time course and possible etiologic factors are discussed.", "contents": "Severe pulmonary hemorrhage following lymphography. The hemoptysis which occurs following lymphography typically consists of one or more episodes of blood-tinged sputum, and generally requires no treatment. In contradistinction to this \"mild\" form of hemoptysis, the current report describes a case of hemoptysis following lymphography--hemoptysis so severe as to require multiple transfusions. Time course and possible etiologic factors are discussed."}
{"id": "PMID:217521", "title": "Myxoid variant of malignant fibrous histiocytoma: ultrastructural observations.", "content": "The ultrastructural findings in 4 cases of the myxoid variant of malignant fibrous histiocytoma (MFH) are described. Although this neoplasm is characterized by a high rate of local recurrence, the overall prognosis is considerably better than the usual nonmyxoid MFH. The neoplasm is composed of an admixture of round, stellate and multinucleated giant cells within a myxoid and well-vascularized stroma. Electron microscopy demonstrated four principal cell types: a primitive mesenchymal cell, spindle cells of fibroblastic and histiocytic nature, and multinucleated giant cells. These observations complement the light microscopic features but probably are insufficient to differentiate critically this entity from other myxomatous lesions of mesenchymal soft tissue such as myxoma, pseudosarcomatous fasciitis, myxoid liposarcoma. The polymorphic cellular composition lends support to the concept that the neoplasm is probably derived from a primitive multipotent mesenchymal cell capable of structural and functional modulation toward more cytodifferentiated forms.", "contents": "Myxoid variant of malignant fibrous histiocytoma: ultrastructural observations. The ultrastructural findings in 4 cases of the myxoid variant of malignant fibrous histiocytoma (MFH) are described. Although this neoplasm is characterized by a high rate of local recurrence, the overall prognosis is considerably better than the usual nonmyxoid MFH. The neoplasm is composed of an admixture of round, stellate and multinucleated giant cells within a myxoid and well-vascularized stroma. Electron microscopy demonstrated four principal cell types: a primitive mesenchymal cell, spindle cells of fibroblastic and histiocytic nature, and multinucleated giant cells. These observations complement the light microscopic features but probably are insufficient to differentiate critically this entity from other myxomatous lesions of mesenchymal soft tissue such as myxoma, pseudosarcomatous fasciitis, myxoid liposarcoma. The polymorphic cellular composition lends support to the concept that the neoplasm is probably derived from a primitive multipotent mesenchymal cell capable of structural and functional modulation toward more cytodifferentiated forms."}
{"id": "PMID:217522", "title": "The problem of carcinoma developing in a fibroadenoma: recent experience at Memorial Hospital.", "content": "Fourteen new cases of unsuspected carcinoma developing in fibroadenomas are reported with a detailed analysis of their preoperative findings; histopathology, the results of varying surgical procedures and a three month to twenty-six year follow-up. The majority of lesions were lobular carcinoma in situ (71%) and 29% of all cases were found to have carcinoma of the contralateral breast. Our study suggests that for invasive carcinoma within a fibroadenoma complete mastectomy is warranted in virtually all instances while noninvasive disease treated by complete mastectomy is essentially curative. Contralateral breast biopsy at the time of diagnosis with a careful life-time follow-up are appropriate because of the high risk of contralateral invasive coarcinoma. There seemed to be no evidence of striking or unusual epithelial hyperplasia in the breast tissue adjacent to fibroadenomas that contained carcinoma suggesting that the carcinomas are not intrinsically different from those not related to fibroadenomas.", "contents": "The problem of carcinoma developing in a fibroadenoma: recent experience at Memorial Hospital. Fourteen new cases of unsuspected carcinoma developing in fibroadenomas are reported with a detailed analysis of their preoperative findings; histopathology, the results of varying surgical procedures and a three month to twenty-six year follow-up. The majority of lesions were lobular carcinoma in situ (71%) and 29% of all cases were found to have carcinoma of the contralateral breast. Our study suggests that for invasive carcinoma within a fibroadenoma complete mastectomy is warranted in virtually all instances while noninvasive disease treated by complete mastectomy is essentially curative. Contralateral breast biopsy at the time of diagnosis with a careful life-time follow-up are appropriate because of the high risk of contralateral invasive coarcinoma. There seemed to be no evidence of striking or unusual epithelial hyperplasia in the breast tissue adjacent to fibroadenomas that contained carcinoma suggesting that the carcinomas are not intrinsically different from those not related to fibroadenomas."}
{"id": "PMID:217523", "title": "Scar cancer of the lung: increase over a 21 year period.", "content": "In a review of 1,186 cases of lung cancer found amoung 7,629 autopsied cases over a 21 year period a total of 82 peripheral cancers related to scars were found, constituting 1% of the autopsied cases and 7% of the lung tumors. 15% of all lung tumors were peripheral (vs. bronchogenic) and the percentage rose from less than 7 in the time period of 1955 to 1960 to a little more than 23 in the 1970 to 1976 time period. 45% of all peripheral lung cancers originated in a scar. Less than 2% of all lung cancers were found associated with scars in the 1955 through 1959 time period. This increased to nearly 16% in the 1970 through 1975 time period. 72% of the scar cancers were adenocarcinomas and 18% were of squamous cell type. The rest were large cell undifferentiated carcinomas and none was oat cell or small cell type. Over three-quarters of these scar cancers were found in the upper lobes and more than half were related to infarcts. Less than a quarter were related to tuberculosis scars. No relationship was found between smoking habits and scar cancer.", "contents": "Scar cancer of the lung: increase over a 21 year period. In a review of 1,186 cases of lung cancer found amoung 7,629 autopsied cases over a 21 year period a total of 82 peripheral cancers related to scars were found, constituting 1% of the autopsied cases and 7% of the lung tumors. 15% of all lung tumors were peripheral (vs. bronchogenic) and the percentage rose from less than 7 in the time period of 1955 to 1960 to a little more than 23 in the 1970 to 1976 time period. 45% of all peripheral lung cancers originated in a scar. Less than 2% of all lung cancers were found associated with scars in the 1955 through 1959 time period. This increased to nearly 16% in the 1970 through 1975 time period. 72% of the scar cancers were adenocarcinomas and 18% were of squamous cell type. The rest were large cell undifferentiated carcinomas and none was oat cell or small cell type. Over three-quarters of these scar cancers were found in the upper lobes and more than half were related to infarcts. Less than a quarter were related to tuberculosis scars. No relationship was found between smoking habits and scar cancer."}
{"id": "PMID:217524", "title": "Prolactin receptors in human breast carcinoma.", "content": "A preliminary investigation into prolactin receptors in human breast carcinomas provided strong evidence that specific binding of prolactin was occurring in at least three of the nine specimens examined (eight human breast carcinomas and one scalp metastasis). These \"prolactin receptor positive\" tumors were all from premenopausal patients. Three of the tumors of postmenopausal women also suggested the occurrence of specific prolactin binding but, as saturation of the receptors had not been achieved in these assays, the results require confirmation. Some general trends in the binding characteristics of the tumors of premenopausal and postmenopausal patients were also observed.", "contents": "Prolactin receptors in human breast carcinoma. A preliminary investigation into prolactin receptors in human breast carcinomas provided strong evidence that specific binding of prolactin was occurring in at least three of the nine specimens examined (eight human breast carcinomas and one scalp metastasis). These \"prolactin receptor positive\" tumors were all from premenopausal patients. Three of the tumors of postmenopausal women also suggested the occurrence of specific prolactin binding but, as saturation of the receptors had not been achieved in these assays, the results require confirmation. Some general trends in the binding characteristics of the tumors of premenopausal and postmenopausal patients were also observed."}
{"id": "PMID:217525", "title": "Endometrial findings in postmenopausal women receiving long-term estrogen therapy.", "content": "An histological study of the endometrium of 43 postmenopausal women under the chronic effect of cyclically administered conjugated estrogens was performed. Four atypical hyperplasias and one adenocarcinoma in situ were found. The frequency of these findings is similar to the one found in a sample of the population consulting the gynecologic clinic of our Hospital that never received estrogen therapy.", "contents": "Endometrial findings in postmenopausal women receiving long-term estrogen therapy. An histological study of the endometrium of 43 postmenopausal women under the chronic effect of cyclically administered conjugated estrogens was performed. Four atypical hyperplasias and one adenocarcinoma in situ were found. The frequency of these findings is similar to the one found in a sample of the population consulting the gynecologic clinic of our Hospital that never received estrogen therapy."}
{"id": "PMID:217526", "title": "Genetic mechanisms in cancer predisposition: report of a cancer family.", "content": "A family is described in which four children developed cancer affecting different organs:lymphoma, meningeal sarcoma, osteogenic sarcoma, and adenocarcinoma of the cecum. Since there was only one other case of cancer in previous generations of this family, an hypothesis is put forth to explain this unusual aggregation on the basis of recombination of common genes. It is postulated that each parent carried a different combination of genes which, though not associated with increased cancer predisposition in the combinations in which they were present in the parents, due to independent assortment resulted in a combination producing cancer susceptibility in half of the offspring. Such genetic loci could include factors similar to an oncogene which is normally held in control by genes at another locus; thus the dominant oncogene without the dominant controlling genes would make for cancer susceptibility, while the controlling genes without the oncogene would be associated with cancer resistance since two mutations would then be required for malignant development. To explain the occurrence of lymphoma in one of the children in this family, a third set of genes is included in this model--genes affecting immunocompetence, in which the normal allele is dominant. This three locus model has the advantage of being able to explain not only the occasional cancer family, but also the distribution of cancer susceptibility and resistance in the general population.", "contents": "Genetic mechanisms in cancer predisposition: report of a cancer family. A family is described in which four children developed cancer affecting different organs:lymphoma, meningeal sarcoma, osteogenic sarcoma, and adenocarcinoma of the cecum. Since there was only one other case of cancer in previous generations of this family, an hypothesis is put forth to explain this unusual aggregation on the basis of recombination of common genes. It is postulated that each parent carried a different combination of genes which, though not associated with increased cancer predisposition in the combinations in which they were present in the parents, due to independent assortment resulted in a combination producing cancer susceptibility in half of the offspring. Such genetic loci could include factors similar to an oncogene which is normally held in control by genes at another locus; thus the dominant oncogene without the dominant controlling genes would make for cancer susceptibility, while the controlling genes without the oncogene would be associated with cancer resistance since two mutations would then be required for malignant development. To explain the occurrence of lymphoma in one of the children in this family, a third set of genes is included in this model--genes affecting immunocompetence, in which the normal allele is dominant. This three locus model has the advantage of being able to explain not only the occasional cancer family, but also the distribution of cancer susceptibility and resistance in the general population."}
{"id": "PMID:217527", "title": "The triad of hemochromatosis, hepatoma and erythrocytosis.", "content": "The triad of hemochromatosis, hepatoma and erythrocytosis is a rare combination. Hemochromatosis is often not recognized until the patient presents with the symptoms of hepatocellular carcinoma and erythrocytosis, and the development of erythrocytosis is an important clue to the under-lying hepatoma. The high serum iron concentration and the high saturation of the iron-binding protein, as well as the typical bone marrow hemosiderin pattern, are important aids in the recognition of hemochromatosis. To date, all patients with this triad have been elderly males. The clinical course is usually one of rapid deterioration and death. The seven previously reported cases have been reviewed and the relationship of the erythrocytosis to the increased production of erythropoietin is discussed.", "contents": "The triad of hemochromatosis, hepatoma and erythrocytosis. The triad of hemochromatosis, hepatoma and erythrocytosis is a rare combination. Hemochromatosis is often not recognized until the patient presents with the symptoms of hepatocellular carcinoma and erythrocytosis, and the development of erythrocytosis is an important clue to the under-lying hepatoma. The high serum iron concentration and the high saturation of the iron-binding protein, as well as the typical bone marrow hemosiderin pattern, are important aids in the recognition of hemochromatosis. To date, all patients with this triad have been elderly males. The clinical course is usually one of rapid deterioration and death. The seven previously reported cases have been reviewed and the relationship of the erythrocytosis to the increased production of erythropoietin is discussed."}
{"id": "PMID:217528", "title": "Primary oat cell carcinoma of the larynx: a case report and review of the literature.", "content": "A case of an extrapulmonary oat cell carcinoma arising in the larynx of a 45-year-old male is described. Ultrastructural study demonstrated numerous neurosecretory granules in the tumor cells identical to those described in oat cell carcinomas of the lung. Primary oat cell carcinomas of the larynx are highly malignant neoplasms. Of six previously reported acceptable cases of this rare entity, with adequate followup, all but one has died of tumor within 14 months of diagnosis. The present patient is alive without evidence of tumor 15 months following diagnosis. Aggressive therapy consisting of a combination of surgery, radiation therapy and systemic chemotherapy was utilized in this case. The use of such aggressive combination therapy appears indicated in cases of primary oat cell carcinoma of the larynx if improved survival is to be achieved.", "contents": "Primary oat cell carcinoma of the larynx: a case report and review of the literature. A case of an extrapulmonary oat cell carcinoma arising in the larynx of a 45-year-old male is described. Ultrastructural study demonstrated numerous neurosecretory granules in the tumor cells identical to those described in oat cell carcinomas of the lung. Primary oat cell carcinomas of the larynx are highly malignant neoplasms. Of six previously reported acceptable cases of this rare entity, with adequate followup, all but one has died of tumor within 14 months of diagnosis. The present patient is alive without evidence of tumor 15 months following diagnosis. Aggressive therapy consisting of a combination of surgery, radiation therapy and systemic chemotherapy was utilized in this case. The use of such aggressive combination therapy appears indicated in cases of primary oat cell carcinoma of the larynx if improved survival is to be achieved."}
{"id": "PMID:217529", "title": "The value of percutaneous needle biopsy in the management of primary bone tumors.", "content": "Thirty-four suspected primary bone neoplasms were evaluated by needle biopsy at M. D. Anderson Hospital and Tumor Institute between September 1976 and February 1978. Adequate material for evaluation was obtained in 31 cases. The accuracy rate of the procedure was 93%. Needle biopsy is a rapid, effective and safe method of evaluating unsuspected primary lesions of bone. The indications, contraindications, and technique are emphasized. The benefits over open biopsy are indicated.", "contents": "The value of percutaneous needle biopsy in the management of primary bone tumors. Thirty-four suspected primary bone neoplasms were evaluated by needle biopsy at M. D. Anderson Hospital and Tumor Institute between September 1976 and February 1978. Adequate material for evaluation was obtained in 31 cases. The accuracy rate of the procedure was 93%. Needle biopsy is a rapid, effective and safe method of evaluating unsuspected primary lesions of bone. The indications, contraindications, and technique are emphasized. The benefits over open biopsy are indicated."}
{"id": "PMID:217531", "title": "Role of superoxide dismutase in cancer: a review.", "content": "Diminished amounts of manganese-containing superoxide dismutase have been found in all the tumors examined to date. Lowered amounts of the copper-zinc-containing superoxide dismutase have been found in many, but not all, tumors. At the same time, tumors have been shown to produce superoxide radicals. It is shown how diminished enzyme activities along with radical production may lead to many of the observed properties of cancer cells. The apparent exploitation of the differences between normal and cancer cell superoxide dismutase activity in the treatment of cancer is discussed.", "contents": "Role of superoxide dismutase in cancer: a review. Diminished amounts of manganese-containing superoxide dismutase have been found in all the tumors examined to date. Lowered amounts of the copper-zinc-containing superoxide dismutase have been found in many, but not all, tumors. At the same time, tumors have been shown to produce superoxide radicals. It is shown how diminished enzyme activities along with radical production may lead to many of the observed properties of cancer cells. The apparent exploitation of the differences between normal and cancer cell superoxide dismutase activity in the treatment of cancer is discussed."}
{"id": "PMID:217534", "title": "Effect of 1-methyl-1-nitrosourea on poly(adenosine diphosphate-ribose) polymerase activity at the nucleosomal level.", "content": "The stimulation of poly(adenosine diphosphate ribose) [poly(ADP-ribose)] polymerase activity at the nuclear level after damage of HeLa cells by 1-methyl-1-nitrosourea has been previously reported. We have observed a similar activation of the enzyme after treatment of cells with MNU at the nucleosomal level of chromatin (greater than 1N). This stimulation of enzyme activity did not occur through an inhibition of the glycohydrolase enzyme which cleaves poly(ADP-ribose), or elongation of poly(ADP-ribose) chains, or an increased biosynthesis of enzyme protein. The increased activity appears to be a consequence of the generation of more acceptor sites on nuclear proteins for initiation of poly(ADP-ribose) synthesis. The data indicate that MNU increased the accessibility of nucleosome core histones for modification by poly(ADP) ribosylation.", "contents": "Effect of 1-methyl-1-nitrosourea on poly(adenosine diphosphate-ribose) polymerase activity at the nucleosomal level. The stimulation of poly(adenosine diphosphate ribose) [poly(ADP-ribose)] polymerase activity at the nuclear level after damage of HeLa cells by 1-methyl-1-nitrosourea has been previously reported. We have observed a similar activation of the enzyme after treatment of cells with MNU at the nucleosomal level of chromatin (greater than 1N). This stimulation of enzyme activity did not occur through an inhibition of the glycohydrolase enzyme which cleaves poly(ADP-ribose), or elongation of poly(ADP-ribose) chains, or an increased biosynthesis of enzyme protein. The increased activity appears to be a consequence of the generation of more acceptor sites on nuclear proteins for initiation of poly(ADP-ribose) synthesis. The data indicate that MNU increased the accessibility of nucleosome core histones for modification by poly(ADP) ribosylation."}
{"id": "PMID:217535", "title": "Nitrosourea interaction with chromatin and effect on poly(adenosine diphosphate ribose) polymerase activity.", "content": "Poly(adenosine diphosphate ribose) polymerase, a chromatin-bound enzyme, was stimulated 150 to 200% after treatment of HeLa cells with methylnitrosourea (MNU). In contrast, a slight inhibitory effect on enzyme activity was observed after treatment of cells with various concentrations of chloroethylnitrosoureas. To define precisely the differential effects of nitrosoureas on the enzyme activity, their interactions with chromatin substructure were studied. A nonrandom, in vivo alkylation of chromatin DNA by equimolar concentrations of MNU and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) was revealed by digestion of nuclei from drug-treated cells with micrococcal nuclease and DNase I. [methyl-14C]MNU interacted preferentially with the more accessible regions of chromatin, the internucleosome linkers, whereas, the [chloroethyl-14C]CCNU alkylated the nucleosomal core DNA to a greater extent. These two drugs also differed in their extent of covalent modification of histone and nonhistone chromosomal protein. The binding of MNU to histones was greater than of CCNU.  CCNU mainly affected nonhistone proteins. This difference in the reactivity of methyl and chloroethyl nitrosoureas with chromatin may relate to their differential effect on poly(adenosine diphosphate ribose) polymerase activity, as well as to their carcinogenic and antitumor properties.", "contents": "Nitrosourea interaction with chromatin and effect on poly(adenosine diphosphate ribose) polymerase activity. Poly(adenosine diphosphate ribose) polymerase, a chromatin-bound enzyme, was stimulated 150 to 200% after treatment of HeLa cells with methylnitrosourea (MNU). In contrast, a slight inhibitory effect on enzyme activity was observed after treatment of cells with various concentrations of chloroethylnitrosoureas. To define precisely the differential effects of nitrosoureas on the enzyme activity, their interactions with chromatin substructure were studied. A nonrandom, in vivo alkylation of chromatin DNA by equimolar concentrations of MNU and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) was revealed by digestion of nuclei from drug-treated cells with micrococcal nuclease and DNase I. [methyl-14C]MNU interacted preferentially with the more accessible regions of chromatin, the internucleosome linkers, whereas, the [chloroethyl-14C]CCNU alkylated the nucleosomal core DNA to a greater extent. These two drugs also differed in their extent of covalent modification of histone and nonhistone chromosomal protein. The binding of MNU to histones was greater than of CCNU.  CCNU mainly affected nonhistone proteins. This difference in the reactivity of methyl and chloroethyl nitrosoureas with chromatin may relate to their differential effect on poly(adenosine diphosphate ribose) polymerase activity, as well as to their carcinogenic and antitumor properties."}
{"id": "PMID:217536", "title": "New side effect of the hypoxic cell sensitizer, misonidazole.", "content": "As part of a phase II study with the hypoxic cell radiosensitizer, misonidazole, we have encountered two cases of dermatitis. When all drugs were withdrawn and the patients were challenged with a small single dose of misonidazole, identical adverse reactions reappeared demonstrating a drug-related skin hypersensitivity.", "contents": "New side effect of the hypoxic cell sensitizer, misonidazole. As part of a phase II study with the hypoxic cell radiosensitizer, misonidazole, we have encountered two cases of dermatitis. When all drugs were withdrawn and the patients were challenged with a small single dose of misonidazole, identical adverse reactions reappeared demonstrating a drug-related skin hypersensitivity."}
{"id": "PMID:217538", "title": "Selective pancreatic vein catheterization for hormone assay in endocrine tumors of the pancreas.", "content": "To evaluate its potential as an alternative to angiography in the diagnosis of pancreatic tumors, we performed selective vein catheterization for hormone assay on 11 patients with islet cell tumors and islet cell hyperplasias. In all patients, the abnormal pancreatic tissue was correctly localized preoperatively by this method.", "contents": "Selective pancreatic vein catheterization for hormone assay in endocrine tumors of the pancreas. To evaluate its potential as an alternative to angiography in the diagnosis of pancreatic tumors, we performed selective vein catheterization for hormone assay on 11 patients with islet cell tumors and islet cell hyperplasias. In all patients, the abnormal pancreatic tissue was correctly localized preoperatively by this method."}
{"id": "PMID:217540", "title": "Ultrastructure and cytochemistry of the yolk syncytial layer in the alevin of trout (Salmo fario trutta L. and Salmo gairdneri R.) after hatching. II. The cytoplasmic zone.", "content": "In contrast to the vitellolysis zone which is involved in the degradation of the yolk, the cytoplasmic zone of the yolk syncytial layer, composed of many cytoplasmic organelles, is implicated in a secretory process. The granular endoplasmic reticulum of the latter is extremely well developed and organized into trabeculae. The yolk nuclei show a RNA positive reaction. The Golgi apparatus is implicated in the elaboration of very low density lipoproteins (VLDL) and of acid phosphatase. The numerous mitochondria seem to suggest an important energy metabolism in the solubilisation area. The appearance of certain special structures (crystalline bodies, pseudovesicular structures, lipochondria) as well as their relation with the organelles of the cytoplasmic zone, re-inforces the impression of a layer with a secretory nature and suggests its participation in the remodelling of the yolk products produced in the vitellolysis zone. The results of the investigations concerning the acid phosphatase activity suggest that this enzyme plays a role on the one hand in the degradation of certain platelets which penetrate into the cytoplasmic zone, and on the other hand in the regulation of VLDL, in the lysis of secretory products elaborated by the cytoplasmic zone. The possible presence of microperoxisomes is discussed as well as the positive detection of glucose-6-phosphate dehydrogenase.", "contents": "Ultrastructure and cytochemistry of the yolk syncytial layer in the alevin of trout (Salmo fario trutta L. and Salmo gairdneri R.) after hatching. II. The cytoplasmic zone. In contrast to the vitellolysis zone which is involved in the degradation of the yolk, the cytoplasmic zone of the yolk syncytial layer, composed of many cytoplasmic organelles, is implicated in a secretory process. The granular endoplasmic reticulum of the latter is extremely well developed and organized into trabeculae. The yolk nuclei show a RNA positive reaction. The Golgi apparatus is implicated in the elaboration of very low density lipoproteins (VLDL) and of acid phosphatase. The numerous mitochondria seem to suggest an important energy metabolism in the solubilisation area. The appearance of certain special structures (crystalline bodies, pseudovesicular structures, lipochondria) as well as their relation with the organelles of the cytoplasmic zone, re-inforces the impression of a layer with a secretory nature and suggests its participation in the remodelling of the yolk products produced in the vitellolysis zone. The results of the investigations concerning the acid phosphatase activity suggest that this enzyme plays a role on the one hand in the degradation of certain platelets which penetrate into the cytoplasmic zone, and on the other hand in the regulation of VLDL, in the lysis of secretory products elaborated by the cytoplasmic zone. The possible presence of microperoxisomes is discussed as well as the positive detection of glucose-6-phosphate dehydrogenase."}
{"id": "PMID:217541", "title": "Localization of corticotropin- and endorphin-related peptides in the intermediate lobe of the rat pituitary.", "content": "The question is examined whether alpha-melanocyte stimulating hormone (alpha-MSH), adrenocorticotropic hormone (ACTH), met-enkephalin and beta-endorphin are detectable by enzyme immunocytochemistry in the cells of the intermediate lobe (PI) of the rat pituitary. By applying antibodies against alpha-MSH, ACTH and beta-endorphin on light microscopic sections, intense immunostaining was found in all PI-cells. At the ultrastructural level, after treatment of consecutive serial sections with these three antibodies the immunoreactivity was localized in the same secretory granules. No specific metenkephalin immunoreactivity could be detected in the cells of the intermediate lobe.", "contents": "Localization of corticotropin- and endorphin-related peptides in the intermediate lobe of the rat pituitary. The question is examined whether alpha-melanocyte stimulating hormone (alpha-MSH), adrenocorticotropic hormone (ACTH), met-enkephalin and beta-endorphin are detectable by enzyme immunocytochemistry in the cells of the intermediate lobe (PI) of the rat pituitary. By applying antibodies against alpha-MSH, ACTH and beta-endorphin on light microscopic sections, intense immunostaining was found in all PI-cells. At the ultrastructural level, after treatment of consecutive serial sections with these three antibodies the immunoreactivity was localized in the same secretory granules. No specific metenkephalin immunoreactivity could be detected in the cells of the intermediate lobe."}
{"id": "PMID:217542", "title": "Immunofluorescence on avian sarcoma virus-transformed cells: localization of the src gene product.", "content": "The localization of the avian sarcoma virus src gene product (termed p60src) was examined by indirect immunofluorescence in cells transformed by the Schmidt-Ruppin strain of Rous sarcoma virus, subgroup D (SR-RSV-D). Antiserum to p60src was obtained from rabbits bearing SR-RSV-D-induced tumors, and immunofluorescence was performed on chicken embryo fibroblasts (CEF) transformed with SR-RSV-D, as well as normal rat kidney (NRK) cells transformed by the same virus (termed SR-RK cells). Both acetone and formaldehyde fixation were used for the immunofluorescence tests. The specificity of the anti-tumor serum was first demonstrated in both cell systems by gel electrophoresis of immunoprecipitates prepared from 35S--methionine-labeled cells. Anti-tumor serum precipitated p60src from SR-RSV-D-transformed CEF but not from CEF infected with a transformation-defective mutant of SR-RSV-D. All viral structural proteins and precursors contained in these immunoprecipitates could be eliminated by competition with unlabeled virus. Similar experiments on SR-RK cells indicated that no viral proteins other than p60src were expressed in these cells, and this observation was supported by immunofluorescence tests using antiserum to whole virus. For immunofluorescence localization of p60src, reactions with viral structural proteins were blocked with unlabeled virus. This presaturation step, obligatory for p60src detection in the SR-RSV-D-transformed CEF, was unnecessary when antitumor serum was tested on SR-RK cells, since p60src was the only viral protein detectable in these cells. With acetone-fixed cells, p60src-specific immunofluorescence revealed a characteristic fluorescence pattern which was similar in both cell systems. The principal pattern was diffuse and situated in the cytoplasm. A clear nuclear fluorescence was never observed. Immunofluorescence on formaldehyde-fixed cells also indicated the cytoplasmic location of p60src and revealed a specific subcytoplasmic concentration of the fluorescence. With both fixation methods, an additional fluorescence pattern was seen between cells in contact, and was also found in both SR-RK cells and SR-RSV-D-transformed CEF. Immunofluorescence on viable cells suggested that p60src was not on the surface of these transformed cells. The fluorescence patterns were specific for avian sarcoma virus-transformed cells and were not found in uninfected cells, cells infected with a transformation-defective mutant of SR-RSV-D or cells transformed by an antigenically unrelated murine sarcoma virus. Furthermore, anti-tumor serum did not contain antibodies to proteins of the microtubules or intermediate filaments.", "contents": "Immunofluorescence on avian sarcoma virus-transformed cells: localization of the src gene product. The localization of the avian sarcoma virus src gene product (termed p60src) was examined by indirect immunofluorescence in cells transformed by the Schmidt-Ruppin strain of Rous sarcoma virus, subgroup D (SR-RSV-D). Antiserum to p60src was obtained from rabbits bearing SR-RSV-D-induced tumors, and immunofluorescence was performed on chicken embryo fibroblasts (CEF) transformed with SR-RSV-D, as well as normal rat kidney (NRK) cells transformed by the same virus (termed SR-RK cells). Both acetone and formaldehyde fixation were used for the immunofluorescence tests. The specificity of the anti-tumor serum was first demonstrated in both cell systems by gel electrophoresis of immunoprecipitates prepared from 35S--methionine-labeled cells. Anti-tumor serum precipitated p60src from SR-RSV-D-transformed CEF but not from CEF infected with a transformation-defective mutant of SR-RSV-D. All viral structural proteins and precursors contained in these immunoprecipitates could be eliminated by competition with unlabeled virus. Similar experiments on SR-RK cells indicated that no viral proteins other than p60src were expressed in these cells, and this observation was supported by immunofluorescence tests using antiserum to whole virus. For immunofluorescence localization of p60src, reactions with viral structural proteins were blocked with unlabeled virus. This presaturation step, obligatory for p60src detection in the SR-RSV-D-transformed CEF, was unnecessary when antitumor serum was tested on SR-RK cells, since p60src was the only viral protein detectable in these cells. With acetone-fixed cells, p60src-specific immunofluorescence revealed a characteristic fluorescence pattern which was similar in both cell systems. The principal pattern was diffuse and situated in the cytoplasm. A clear nuclear fluorescence was never observed. Immunofluorescence on formaldehyde-fixed cells also indicated the cytoplasmic location of p60src and revealed a specific subcytoplasmic concentration of the fluorescence. With both fixation methods, an additional fluorescence pattern was seen between cells in contact, and was also found in both SR-RK cells and SR-RSV-D-transformed CEF. Immunofluorescence on viable cells suggested that p60src was not on the surface of these transformed cells. The fluorescence patterns were specific for avian sarcoma virus-transformed cells and were not found in uninfected cells, cells infected with a transformation-defective mutant of SR-RSV-D or cells transformed by an antigenically unrelated murine sarcoma virus. Furthermore, anti-tumor serum did not contain antibodies to proteins of the microtubules or intermediate filaments."}
{"id": "PMID:217544", "title": "Characterization of cross-reacting antigens on the Epstein-Barr virus envelope and plasma membranes of producer cells.", "content": "A rabbit antiserum has been prepared against the B95-8 transforming strain of EBV. The antiserum has a high virus neutralizing titer (approximately 1:1000) against both the marmoset B95-8 EBV and the human P3HR-1 EBV. The neutralizing antibodies may be absorbed completely with EBV producer cell lines, but not with nonproducer cell lines or producer cell lines treated with phosphonoacetic acid (PAA) so as to be nonproducer. After repeated absorption with PAA-treated B95-8, the serum remains reactive with the membranes of producer cell lines as judged by immunofluorescence or the 125I--Staphylococcal protein A radioimmunoassay. Thus the neutralizing antigens are expressed on the membranes of producer cell lines and may be purified from this source using the serum and 125I--Staph A binding as an assay. The ability of the serum to differentiate between producer and nonproducer cells by means of cell surface determinants has been exploited to achieve a separation of these two populations from the same culture. Immunoprecipitation by the protein A technique shows that the serum recognizes two polypeptides from producer cells of approximate molecular weights 150,000 and 75,000.", "contents": "Characterization of cross-reacting antigens on the Epstein-Barr virus envelope and plasma membranes of producer cells. A rabbit antiserum has been prepared against the B95-8 transforming strain of EBV. The antiserum has a high virus neutralizing titer (approximately 1:1000) against both the marmoset B95-8 EBV and the human P3HR-1 EBV. The neutralizing antibodies may be absorbed completely with EBV producer cell lines, but not with nonproducer cell lines or producer cell lines treated with phosphonoacetic acid (PAA) so as to be nonproducer. After repeated absorption with PAA-treated B95-8, the serum remains reactive with the membranes of producer cell lines as judged by immunofluorescence or the 125I--Staphylococcal protein A radioimmunoassay. Thus the neutralizing antigens are expressed on the membranes of producer cell lines and may be purified from this source using the serum and 125I--Staph A binding as an assay. The ability of the serum to differentiate between producer and nonproducer cells by means of cell surface determinants has been exploited to achieve a separation of these two populations from the same culture. Immunoprecipitation by the protein A technique shows that the serum recognizes two polypeptides from producer cells of approximate molecular weights 150,000 and 75,000."}
{"id": "PMID:217545", "title": "RNA sequencing provides evidence for allelism of determinants of the N-, B- or NB-tropism of murine leukemia viruses.", "content": "Previous genetic and biochemical studies identified three large RNAase T1-resistant oligonucleotides, each associated with either the N-, B- or NB-tropism of murine C-type viruses of BALB/c origin. These oligonucleotides were shown to lie in the 5' third of the oligonucleotide maps of their respective viruses. We sequenced the three oligonucleotides and found that they share a 10 base sequence. Together these observations provide good evidence that the determinants of N-, B- or NB-tropism monitored by the three oligonucleotides are allelic. The oligonucleotides associated with N- and B-tropism differ in sequence at four of sixteen nucleotides, while the B- and NB-tropism-associated oligonucleotides differ in sequence by only one base out of sixteen. These results are consistent with the possibilities that B-tropic viruses may arise from N-tropic viruses by recombination, while NB-tropic viruses may arise from B-tropic virus by mutation. An unexplained finding was that a 10 base sequence present in the oligonucleotide associated with N-tropism is also found in the 3' third of the genomes of the N-, B- and NB-tropic viruses studied.", "contents": "RNA sequencing provides evidence for allelism of determinants of the N-, B- or NB-tropism of murine leukemia viruses. Previous genetic and biochemical studies identified three large RNAase T1-resistant oligonucleotides, each associated with either the N-, B- or NB-tropism of murine C-type viruses of BALB/c origin. These oligonucleotides were shown to lie in the 5' third of the oligonucleotide maps of their respective viruses. We sequenced the three oligonucleotides and found that they share a 10 base sequence. Together these observations provide good evidence that the determinants of N-, B- or NB-tropism monitored by the three oligonucleotides are allelic. The oligonucleotides associated with N- and B-tropism differ in sequence at four of sixteen nucleotides, while the B- and NB-tropism-associated oligonucleotides differ in sequence by only one base out of sixteen. These results are consistent with the possibilities that B-tropic viruses may arise from N-tropic viruses by recombination, while NB-tropic viruses may arise from B-tropic virus by mutation. An unexplained finding was that a 10 base sequence present in the oligonucleotide associated with N-tropism is also found in the 3' third of the genomes of the N-, B- and NB-tropic viruses studied."}
{"id": "PMID:217546", "title": "DNA of noninfectious and infectious integrated spleen necrosis virus (SNV) is colinear with unintegrated SNV DNA and not grossly abnormal.", "content": "The cleavage sites of eight restriction endonucleases in linear spleen necrosis virus (SNV) DNA were mapped, and the map was oriented with respect to viral RNA. With the aid of this map, several structural features of the viral DNA were elucidated: unintegrated linear SNV DNA is terminally redundant; the majority of SNV DNA molecules integrated in chicken DNA, which were previously shown to be present in many sites in cellular DNA, are colinear with unintegrated viral DNA; no tandem integration of proviral molecules is detectable; and the majority of integrated SNV DNA molecules, including integrated SNV DNA molecules previously shown to be noninfectious, do not have an altered restriction enzyme digestion pattern.", "contents": "DNA of noninfectious and infectious integrated spleen necrosis virus (SNV) is colinear with unintegrated SNV DNA and not grossly abnormal. The cleavage sites of eight restriction endonucleases in linear spleen necrosis virus (SNV) DNA were mapped, and the map was oriented with respect to viral RNA. With the aid of this map, several structural features of the viral DNA were elucidated: unintegrated linear SNV DNA is terminally redundant; the majority of SNV DNA molecules integrated in chicken DNA, which were previously shown to be present in many sites in cellular DNA, are colinear with unintegrated viral DNA; no tandem integration of proviral molecules is detectable; and the majority of integrated SNV DNA molecules, including integrated SNV DNA molecules previously shown to be noninfectious, do not have an altered restriction enzyme digestion pattern."}
{"id": "PMID:217552", "title": "[Opiate receptor sites in neuronal and glial cell lines in culture].", "content": "A stereospecific saturable high affinity binding of 3H-naloxone has been found in 3 glial and 2 neuronal cell lines. Kinetic study of binding seems to indicate only one class of receptor sites in the 5 cell lines. Acute exposure to morphine (1 X 10(-5)M) concurrent with PGE1-induced stimulation of adenylate cyclase did not result in a decrease of the cAMP level in any cell line tested.", "contents": "[Opiate receptor sites in neuronal and glial cell lines in culture]. A stereospecific saturable high affinity binding of 3H-naloxone has been found in 3 glial and 2 neuronal cell lines. Kinetic study of binding seems to indicate only one class of receptor sites in the 5 cell lines. Acute exposure to morphine (1 X 10(-5)M) concurrent with PGE1-induced stimulation of adenylate cyclase did not result in a decrease of the cAMP level in any cell line tested."}
{"id": "PMID:217553", "title": "[Experimental dissociation between hippocampal theta activity in wakefulness and hippocampal theta activity in paradoxal sleep in the rat].", "content": "The effects of electrolytic lesion of the septum on the theta activity of the dorsal hippocampus were studied in the chronically implanted Rat during wakefulness and paradoxical sleep. The experimental results show that depending on its localization, septal lesion can either: (1) eliminate the wakefulness theta rhythm without suppressing that of paradoxical sleep; (2) eliminate the paradoxical sleep theta rhythm without suppressing that of wakefulness. These results suggest that there are two kinds of theta activity having different anatomophysiological bases and a different functional significance: one associated with wakefulness and the other with paradoxical sleep.", "contents": "[Experimental dissociation between hippocampal theta activity in wakefulness and hippocampal theta activity in paradoxal sleep in the rat]. The effects of electrolytic lesion of the septum on the theta activity of the dorsal hippocampus were studied in the chronically implanted Rat during wakefulness and paradoxical sleep. The experimental results show that depending on its localization, septal lesion can either: (1) eliminate the wakefulness theta rhythm without suppressing that of paradoxical sleep; (2) eliminate the paradoxical sleep theta rhythm without suppressing that of wakefulness. These results suggest that there are two kinds of theta activity having different anatomophysiological bases and a different functional significance: one associated with wakefulness and the other with paradoxical sleep."}
{"id": "PMID:217550", "title": "[Epidemiological study of pulmonary hydatid cyst in the Ivory Coast. 3 cases].", "content": "No cases of echinococcus have been reported up to this time in Ivory Coast, where it has been considered non-existant in either pulmonary or hepatic form. The three cases of pulmonary echinococcus reported here show the classic paucity of clinical symptoms  associated with classical radiological findings. The epidemiological research confirms in one case definite infection occurring in Ivory Coast and the other two either in the Ivory Coast or in closely neighbouring areas.", "contents": "[Epidemiological study of pulmonary hydatid cyst in the Ivory Coast. 3 cases]. No cases of echinococcus have been reported up to this time in Ivory Coast, where it has been considered non-existant in either pulmonary or hepatic form. The three cases of pulmonary echinococcus reported here show the classic paucity of clinical symptoms  associated with classical radiological findings. The epidemiological research confirms in one case definite infection occurring in Ivory Coast and the other two either in the Ivory Coast or in closely neighbouring areas."}
{"id": "PMID:217555", "title": "[Cyclic AMP and control of ion exchanges in the fish intestine].", "content": "In isolated intestine of the European Flounder, cyclic AMP and theophylline induce a reduction of the negative transmural potential difference and short circuit current, increase severalfold the passive permeability for chloride and abolish the active transport of this ion. These effects are very different from those described in mammals.", "contents": "[Cyclic AMP and control of ion exchanges in the fish intestine]. In isolated intestine of the European Flounder, cyclic AMP and theophylline induce a reduction of the negative transmural potential difference and short circuit current, increase severalfold the passive permeability for chloride and abolish the active transport of this ion. These effects are very different from those described in mammals."}
{"id": "PMID:217556", "title": "Toluene di-isocyanate-induced asthma. I. Reactions to TDI, MDI, HDI and histamine.", "content": "A group of twenty four workers handling di-isocyanates and with respiratory disease were investigated by occupational-type bronchial provocation tests for sensitivity to toluene di-isocyanate (TDI), to which all were exposed, and to diphenylmethane di-isocyanate (MDI) and hexamethylene di-isocyanate (HDI). Sixteen gave asthmatic reactions to TDI and eight of these also reacted to MDI. Four of the eight TDI and MDI reactors had histories of exposure only to TDI, and of them two reacted also to HDI. Of nine subjects tested with HDI, three gave asthmatic reactions, and all three also reacted to TDI and MDI. Thus reactions to MDI and HDI were elicited only in the TDI reactors. The possibility of specific sensitivity to these and other di-isocyanates requires tests in subjects exposed to them and not to TDI.", "contents": "Toluene di-isocyanate-induced asthma. I. Reactions to TDI, MDI, HDI and histamine. A group of twenty four workers handling di-isocyanates and with respiratory disease were investigated by occupational-type bronchial provocation tests for sensitivity to toluene di-isocyanate (TDI), to which all were exposed, and to diphenylmethane di-isocyanate (MDI) and hexamethylene di-isocyanate (HDI). Sixteen gave asthmatic reactions to TDI and eight of these also reacted to MDI. Four of the eight TDI and MDI reactors had histories of exposure only to TDI, and of them two reacted also to HDI. Of nine subjects tested with HDI, three gave asthmatic reactions, and all three also reacted to TDI and MDI. Thus reactions to MDI and HDI were elicited only in the TDI reactors. The possibility of specific sensitivity to these and other di-isocyanates requires tests in subjects exposed to them and not to TDI."}
{"id": "PMID:217557", "title": "Toluene di-isocyanate-induced asthma. II. Inhalation challenge tests and bronchial reactivity studies.", "content": "In sixty-three workers exposed to toluene di-isocyanate (TDI), no overall differences in bronchial reactivity to histamine inhalation and to exercise testing were found between the total groups of positive and negative TDI reactors to provocation tests. A subgroup of TDI highly sensitive subjects reacting to very low concentrations (less than or equal to 0.001 p.p.m.) were more sensitive to both histamine and exercise than the group who were less sensitive to TDI, and who reacted to higher concentrations (0.002--0.02 p.p.m.) than the group of non-reactors. There were, however, in the last group a number of subjects with high degrees of histamine reactivity who did not react to the TDI. These findings suggest that, on the one hand, the asthmatic reactions to TDI cannot be attributed solely to non-specific mechanisms and, on the other, that in subjects with high degrees of specific sensitivity non-specific mechanisms may also be playing a part.", "contents": "Toluene di-isocyanate-induced asthma. II. Inhalation challenge tests and bronchial reactivity studies. In sixty-three workers exposed to toluene di-isocyanate (TDI), no overall differences in bronchial reactivity to histamine inhalation and to exercise testing were found between the total groups of positive and negative TDI reactors to provocation tests. A subgroup of TDI highly sensitive subjects reacting to very low concentrations (less than or equal to 0.001 p.p.m.) were more sensitive to both histamine and exercise than the group who were less sensitive to TDI, and who reacted to higher concentrations (0.002--0.02 p.p.m.) than the group of non-reactors. There were, however, in the last group a number of subjects with high degrees of histamine reactivity who did not react to the TDI. These findings suggest that, on the one hand, the asthmatic reactions to TDI cannot be attributed solely to non-specific mechanisms and, on the other, that in subjects with high degrees of specific sensitivity non-specific mechanisms may also be playing a part."}
{"id": "PMID:217566", "title": "Renal function studies using 99mTc-dimercaptosuccinic acid.", "content": "99mTc-dimercaptosuccinic acid (DMSA), provides both a well defined renal image via preferential cortical accumulation, and a quantitative assessment of separate kidney function, correlating well with renal plasma flow obtained from the 131I-Hippuran renogram of each kidney. 99mTc-DMSA is capable of labeling the functioning nephrons in the cortex without interference by the activity of urine flow, suggesting that DMSA should be termed a cortical tubular marker. 99mTc-DMSA scintigraphy has advantages over conventional methods in that it can be performed repeatedly with little discomfort to the patients, as a routine clinical examination.", "contents": "Renal function studies using 99mTc-dimercaptosuccinic acid. 99mTc-dimercaptosuccinic acid (DMSA), provides both a well defined renal image via preferential cortical accumulation, and a quantitative assessment of separate kidney function, correlating well with renal plasma flow obtained from the 131I-Hippuran renogram of each kidney. 99mTc-DMSA is capable of labeling the functioning nephrons in the cortex without interference by the activity of urine flow, suggesting that DMSA should be termed a cortical tubular marker. 99mTc-DMSA scintigraphy has advantages over conventional methods in that it can be performed repeatedly with little discomfort to the patients, as a routine clinical examination."}
{"id": "PMID:217567", "title": "Treatment of pompholyx due to nickel allergy with chelating agents.", "content": "Ingestion of nickel is important for the chronicity of hand eczema in nickel-sensitive patients. We have tried the effect of chelating agents. Diethyldithiocarbamate (DDC) and tetraethyl thiuramdisulfide (TETD) have proved effective in the treatment of nickel carbonyl poisoning. A 66-year-old woman suffering from severe nickel dermatitis has been treated in three periods, first with DDC 100 mg Q. I. D. for 20 days, and later with TETD 100 mg T. I. D. for two  periods. An improvement has been observed in all three experiments.", "contents": "Treatment of pompholyx due to nickel allergy with chelating agents. Ingestion of nickel is important for the chronicity of hand eczema in nickel-sensitive patients. We have tried the effect of chelating agents. Diethyldithiocarbamate (DDC) and tetraethyl thiuramdisulfide (TETD) have proved effective in the treatment of nickel carbonyl poisoning. A 66-year-old woman suffering from severe nickel dermatitis has been treated in three periods, first with DDC 100 mg Q. I. D. for 20 days, and later with TETD 100 mg T. I. D. for two  periods. An improvement has been observed in all three experiments."}
{"id": "PMID:217570", "title": "Hypothalamic-pituitary-adrenal function in extrinsic asthma.", "content": "Hypothalamic-pituitary-adrenal function in a well-defined, carefully selected group of 25 patients with extrinsic asthma was assessed by measuring plasma levels of adrenocorticotropic hormone (ACTH) and of 11-deoxycorticol after administration of metyrapone and by measuring the level of cortisol following stimulation with cosyntropin. No difference was demonstrated between asthmatic subjects and 20 normal age-matched controls. In addition, neither the response of the level of ACTH nor of 11-deoxycortisol correlated with the duration of asthma or the severity as assessed in 23 patients by tests of pulmonary function. We conclude that there is no abnormality in hypothalamic-pituitary-adrenal function in patients with extrinsic asthma, and we suggest that previous data suggesting such an abnormality may reflect heterogeneous groups of patients, inaccurate methods, and the variability of normal responses to ACTH and stimulation with metyrapone.", "contents": "Hypothalamic-pituitary-adrenal function in extrinsic asthma. Hypothalamic-pituitary-adrenal function in a well-defined, carefully selected group of 25 patients with extrinsic asthma was assessed by measuring plasma levels of adrenocorticotropic hormone (ACTH) and of 11-deoxycorticol after administration of metyrapone and by measuring the level of cortisol following stimulation with cosyntropin. No difference was demonstrated between asthmatic subjects and 20 normal age-matched controls. In addition, neither the response of the level of ACTH nor of 11-deoxycortisol correlated with the duration of asthma or the severity as assessed in 23 patients by tests of pulmonary function. We conclude that there is no abnormality in hypothalamic-pituitary-adrenal function in patients with extrinsic asthma, and we suggest that previous data suggesting such an abnormality may reflect heterogeneous groups of patients, inaccurate methods, and the variability of normal responses to ACTH and stimulation with metyrapone."}
{"id": "PMID:217571", "title": "Pulmonary malignant fibrous histiocytoma. Light and electron microscopic studies of one case.", "content": "A malignant fibrous histiocytoma (MFH) arising in the lungs of a 51-year-old man was studied by light and electron microscopy. Features observed were identical to those of MFHs which occur in the skin and subcutaneous tissue and less commonly in other deep locations. By light microscopy, a storiform pattern with admixture of fibroblasts and histiocytes, as well as xanthomatous and giant cells, was noted. Undifferentiated tumor cells along with fibroblasts and histiocytes in different degrees of differentiation were identified ultrastructurally. These findings lend support to the concept that MFH is a sarcoma of primitive mesenchymal cell origin. The addition of the lung as another primary site for the development of this tumor is consistent with the view that MFHs may potentially arise in any part of the body.", "contents": "Pulmonary malignant fibrous histiocytoma. Light and electron microscopic studies of one case. A malignant fibrous histiocytoma (MFH) arising in the lungs of a 51-year-old man was studied by light and electron microscopy. Features observed were identical to those of MFHs which occur in the skin and subcutaneous tissue and less commonly in other deep locations. By light microscopy, a storiform pattern with admixture of fibroblasts and histiocytes, as well as xanthomatous and giant cells, was noted. Undifferentiated tumor cells along with fibroblasts and histiocytes in different degrees of differentiation were identified ultrastructurally. These findings lend support to the concept that MFH is a sarcoma of primitive mesenchymal cell origin. The addition of the lung as another primary site for the development of this tumor is consistent with the view that MFHs may potentially arise in any part of the body."}
{"id": "PMID:217572", "title": "Urinary excretion of mecillinam by volunteers receiving film-coated tablets of pivmecillinam hydrochloride.", "content": "Mecillinam is a new amidinopenicillin which is taken orally as its ester pivmecillinam. 10 healthy volunteers were each given 200 mg of pivmecillinam hydrochloride four times daily and all urine was collected and cooled to -20 degrees C to minimize antibiotic degradation. 43% of the ingested antibiotic was recovered from the urine in its microbiologically active form, during the first 12 h and 34% during the subsequent 24 h. The corresponding figures for 10 volunteers receiving double this dose of antibiotic was 30 and 34%. The mean half life of mecillinam in urine due to spontaneous breakdown at 37 degrees C was 17 h. There was evidence that stearate-film-coated pivmecillinam hydrochloride tablets may be less likely to cause dyspepsia than gelatine capsules.", "contents": "Urinary excretion of mecillinam by volunteers receiving film-coated tablets of pivmecillinam hydrochloride. Mecillinam is a new amidinopenicillin which is taken orally as its ester pivmecillinam. 10 healthy volunteers were each given 200 mg of pivmecillinam hydrochloride four times daily and all urine was collected and cooled to -20 degrees C to minimize antibiotic degradation. 43% of the ingested antibiotic was recovered from the urine in its microbiologically active form, during the first 12 h and 34% during the subsequent 24 h. The corresponding figures for 10 volunteers receiving double this dose of antibiotic was 30 and 34%. The mean half life of mecillinam in urine due to spontaneous breakdown at 37 degrees C was 17 h. There was evidence that stearate-film-coated pivmecillinam hydrochloride tablets may be less likely to cause dyspepsia than gelatine capsules."}
{"id": "PMID:217582", "title": "Effect of thyrotoxicosis on gluconeogenesis from alanine in the perfused rat liver.", "content": "The influence and mechanism of action of T4 treatment on hepatic gluconeogenesis from alanine was studied in isolated rat livers. Conversion of alanine into glucose was increased markedly in livers of thyrotoxic rats compared to that in normal rats. Estimation of metabolic intermediates of the gluconeogenic pathway showed that T4 treatment produced forward cross-over between pyruvate and phosphoenolpyruvate, which suggests that this point is a control site. Alanine transport into the liver cells was apparently active since the alanine level was higher within the hepatocytes than in the extracellular space. Furthermore, T4 treatment stimulated the transport of alanine into the liver cells. alpha-Aminoisobutyric acid uptake was significantly higher by liver of thyrotoxic animals than of normal rats. The hepatic level of cAMP was also higher in experimental livers than control livers. These studies suggest that T4 stimulates hepatic gluconeogenesis from alanine and the underlying mechanism involves an increase in both the transport of amino acid into the liver cell and the conversion pyruvate to phosphoenolpyruvate.", "contents": "Effect of thyrotoxicosis on gluconeogenesis from alanine in the perfused rat liver. The influence and mechanism of action of T4 treatment on hepatic gluconeogenesis from alanine was studied in isolated rat livers. Conversion of alanine into glucose was increased markedly in livers of thyrotoxic rats compared to that in normal rats. Estimation of metabolic intermediates of the gluconeogenic pathway showed that T4 treatment produced forward cross-over between pyruvate and phosphoenolpyruvate, which suggests that this point is a control site. Alanine transport into the liver cells was apparently active since the alanine level was higher within the hepatocytes than in the extracellular space. Furthermore, T4 treatment stimulated the transport of alanine into the liver cells. alpha-Aminoisobutyric acid uptake was significantly higher by liver of thyrotoxic animals than of normal rats. The hepatic level of cAMP was also higher in experimental livers than control livers. These studies suggest that T4 stimulates hepatic gluconeogenesis from alanine and the underlying mechanism involves an increase in both the transport of amino acid into the liver cell and the conversion pyruvate to phosphoenolpyruvate."}
{"id": "PMID:217583", "title": "Reversal of dexamethasone inhibition of adrenocorticotropin release in a mouse pituitary tumor cell line either by growing cells in the absence of dexamethasone or by addition of hypothalamic extract.", "content": "Release of ACTH by a mouse pituitary tumor cell line )AtT-20/D-16v) is inhibited by 10(-8)-10(-6) M 9 alpha-fluoro-16 alpha-methyl-11 beta, 17 alpha, 21-trihydroxy-1,4-pregnadiene-3,20-dione (dexamethasone). Dexamethasone does not inhibit cell growth in this concentration range. Cortisol and corticosterone are almost as potent as dexamethasone in inhibiting ACTH release, whereas 17 beta-estradiol and testosterone have no effect. In rapidly growing cultures of tumor cells removal of dexamethasone leads to complete reversal of the inhibitory effect of the steroid on ACTH accumulation in culture medium within 4-5 days (3.5-4 generation times). The extent of reversal of the dexamethasone effect in slowly growing cultures (generation time 96-150 h) and in rapidly growing cultures (24-30 h) is proportional to the amount of growth that takes place in the absence of dexamethasone. Addition of hypothalamic extract to dexamethasone-treated cultures and to untreated cultures stimulates the release of ACTH 4- to 8-fold. The response occurs within 15 min after the addition of the extract and is dependent on the dose of the extract.", "contents": "Reversal of dexamethasone inhibition of adrenocorticotropin release in a mouse pituitary tumor cell line either by growing cells in the absence of dexamethasone or by addition of hypothalamic extract. Release of ACTH by a mouse pituitary tumor cell line )AtT-20/D-16v) is inhibited by 10(-8)-10(-6) M 9 alpha-fluoro-16 alpha-methyl-11 beta, 17 alpha, 21-trihydroxy-1,4-pregnadiene-3,20-dione (dexamethasone). Dexamethasone does not inhibit cell growth in this concentration range. Cortisol and corticosterone are almost as potent as dexamethasone in inhibiting ACTH release, whereas 17 beta-estradiol and testosterone have no effect. In rapidly growing cultures of tumor cells removal of dexamethasone leads to complete reversal of the inhibitory effect of the steroid on ACTH accumulation in culture medium within 4-5 days (3.5-4 generation times). The extent of reversal of the dexamethasone effect in slowly growing cultures (generation time 96-150 h) and in rapidly growing cultures (24-30 h) is proportional to the amount of growth that takes place in the absence of dexamethasone. Addition of hypothalamic extract to dexamethasone-treated cultures and to untreated cultures stimulates the release of ACTH 4- to 8-fold. The response occurs within 15 min after the addition of the extract and is dependent on the dose of the extract."}
{"id": "PMID:217586", "title": "Stimulation of prostaglandin accumulation in preovulatory rat follicles by adenosine 3',5'-monophosphate.", "content": "LH stimulates an increase in prostaglandins in vitro in preovulatory follicles from rats pretreated with PMS gonadotropin. The role of cAMP in this action of LH was examined by incubating preovulatory follicles with various substances and determining the resultant prostaglandin (PG) E accumulation by radioimmunoassay. LH (5 microgram/ml) increased PGE accumulation to approximately 4 times the control (181 +/- 23 to 886 +/- 83 pg/follicle). The addition of 20 mM cAMP also stimulated PGE accumulation, and the addition of 20 mM cAMP in the presence of 0.5 mM 1-methyl-3-isobutylxanthine was as effective as LH. Other nucleotides such as ATP, ADP, 3'-AMP, 5'-AMP, cGMP, and O2'-monobutyryl-cAMP did not stimulate PGE accumulation. On the other hand, (Bu)2cAMP, 8-bromo-cAMP, and N6-monobutyryl-cAMP produced an increase in PGE accumulation similar to that observed with LH. In addition, 10 microgram/ml cholera toxin was shown to increase both cAMP and PGE accumulation in preovulatory follicles. These results indicate that the prostaglandin response of follicles is specific for cAMP-like nucleotides or substances capable of increasing intracellular cAMP. The data support the concept that cAMP mediates the effect of LH on PGE accumulation in preovulatory follicles in the rat.", "contents": "Stimulation of prostaglandin accumulation in preovulatory rat follicles by adenosine 3',5'-monophosphate. LH stimulates an increase in prostaglandins in vitro in preovulatory follicles from rats pretreated with PMS gonadotropin. The role of cAMP in this action of LH was examined by incubating preovulatory follicles with various substances and determining the resultant prostaglandin (PG) E accumulation by radioimmunoassay. LH (5 microgram/ml) increased PGE accumulation to approximately 4 times the control (181 +/- 23 to 886 +/- 83 pg/follicle). The addition of 20 mM cAMP also stimulated PGE accumulation, and the addition of 20 mM cAMP in the presence of 0.5 mM 1-methyl-3-isobutylxanthine was as effective as LH. Other nucleotides such as ATP, ADP, 3'-AMP, 5'-AMP, cGMP, and O2'-monobutyryl-cAMP did not stimulate PGE accumulation. On the other hand, (Bu)2cAMP, 8-bromo-cAMP, and N6-monobutyryl-cAMP produced an increase in PGE accumulation similar to that observed with LH. In addition, 10 microgram/ml cholera toxin was shown to increase both cAMP and PGE accumulation in preovulatory follicles. These results indicate that the prostaglandin response of follicles is specific for cAMP-like nucleotides or substances capable of increasing intracellular cAMP. The data support the concept that cAMP mediates the effect of LH on PGE accumulation in preovulatory follicles in the rat."}
{"id": "PMID:217588", "title": "Specificity of the immunocytochemical luteinizing hormone-releasing hormone receptor reaction.", "content": "Affinity-purified anti-LHRH, affinity-purified LHRH-anti-LHRH complex, as well as antisera depleted of anti-LHRH by solid phase immunoabsorption were used to test the specificity of the immunocytochemical approach for detection of receptor-bound LHRH. The solid phase immunoabsorbent was prepared by attaching LHRH to Sepharose via an RNase spacer. Purified anti-LHRH was eluted from the immunoabsorbent by acidification. Unabsorbed antisera as well as purified antibody conferred moderate immunocytochemical staining to the secretion granules of rat pituitary gonadotrophs. Staining intensity became greatly increased upon treatment of the electron microscopic sections with LHRH before immunocytochemical staining. All gonadotroph staining was abolished when absorbed antisera were used. The specificity of the immunoabsorbent was tested on mixtures of anti-LHRH and anti-ACTH17-39. On absorption of such mixtures with insolubilized LHRH, all gonadotroph staining disappeared, but the optical density indices of ACTH staining remained unaffected. It is concluded that gonadotroph secretion granules contain, in addition to an LHRH receptor reacting with LHRH in vitro, stable complexes of endogenous LHRH with receptor.", "contents": "Specificity of the immunocytochemical luteinizing hormone-releasing hormone receptor reaction. Affinity-purified anti-LHRH, affinity-purified LHRH-anti-LHRH complex, as well as antisera depleted of anti-LHRH by solid phase immunoabsorption were used to test the specificity of the immunocytochemical approach for detection of receptor-bound LHRH. The solid phase immunoabsorbent was prepared by attaching LHRH to Sepharose via an RNase spacer. Purified anti-LHRH was eluted from the immunoabsorbent by acidification. Unabsorbed antisera as well as purified antibody conferred moderate immunocytochemical staining to the secretion granules of rat pituitary gonadotrophs. Staining intensity became greatly increased upon treatment of the electron microscopic sections with LHRH before immunocytochemical staining. All gonadotroph staining was abolished when absorbed antisera were used. The specificity of the immunoabsorbent was tested on mixtures of anti-LHRH and anti-ACTH17-39. On absorption of such mixtures with insolubilized LHRH, all gonadotroph staining disappeared, but the optical density indices of ACTH staining remained unaffected. It is concluded that gonadotroph secretion granules contain, in addition to an LHRH receptor reacting with LHRH in vitro, stable complexes of endogenous LHRH with receptor."}
{"id": "PMID:217589", "title": "Effect of gonadal steroids on the luteinizing hormone and follicle-stimulating hormone response to 8-bromo-adenosine 3',5'-monophosphate in anterior pituitary cells in culture.", "content": "-8-Bromo-cAMP stimulated the release of LH (approximately 20-fold) and FSH (approximately 2-fold) in control rat anterior pituitary cells in primary culture. 8-Bromo-cAMP-induced LH release was 2-3 times greater in cells preincubated for 48 h in the presence of 10(-8) M 17 beta-estradiol (E2). The LH response to 10(-10) M LHRH was similarly increased by E2 pretreatment whereas progesterone (P), which had no effect on the response to 8-bromo-cAMP, led to a reduction of the stimulatory effect of E2 on the LH response to the neurohormone. Preincubation with 10(-8) M testosterone (T) decreased the LH response to 8-bromo-cAMP by about 40%, whereas the response to LHRH was 80% inhibited. 8-Bromo-cAMP-induced FSH release was slightly increased in cells preincubated with E2 but was greatly augmented in cells treated with E2 + P. Basal FSH release was slightly increased (40%) after preincubation with P or T whereas the response to 8-bromo-cAMP was not significantly affected. The sensitivity of the FSH response to LHRH was increased by E2 whereas P and T led to a stimulation of the maximal FSH response to LHRH with no significant effect on the LHRH ED50 value. The present data indicate that P and E2 exert their effects on LH and FSH release at steps before and after cAMP formation, respectively. T appears to act at both steps on the release of the two gonadotropins.", "contents": "Effect of gonadal steroids on the luteinizing hormone and follicle-stimulating hormone response to 8-bromo-adenosine 3',5'-monophosphate in anterior pituitary cells in culture. -8-Bromo-cAMP stimulated the release of LH (approximately 20-fold) and FSH (approximately 2-fold) in control rat anterior pituitary cells in primary culture. 8-Bromo-cAMP-induced LH release was 2-3 times greater in cells preincubated for 48 h in the presence of 10(-8) M 17 beta-estradiol (E2). The LH response to 10(-10) M LHRH was similarly increased by E2 pretreatment whereas progesterone (P), which had no effect on the response to 8-bromo-cAMP, led to a reduction of the stimulatory effect of E2 on the LH response to the neurohormone. Preincubation with 10(-8) M testosterone (T) decreased the LH response to 8-bromo-cAMP by about 40%, whereas the response to LHRH was 80% inhibited. 8-Bromo-cAMP-induced FSH release was slightly increased in cells preincubated with E2 but was greatly augmented in cells treated with E2 + P. Basal FSH release was slightly increased (40%) after preincubation with P or T whereas the response to 8-bromo-cAMP was not significantly affected. The sensitivity of the FSH response to LHRH was increased by E2 whereas P and T led to a stimulation of the maximal FSH response to LHRH with no significant effect on the LHRH ED50 value. The present data indicate that P and E2 exert their effects on LH and FSH release at steps before and after cAMP formation, respectively. T appears to act at both steps on the release of the two gonadotropins."}
{"id": "PMID:217593", "title": "Effects of thyrotropin on thyroglobulin exocytosis and iodination in the rat thyroid gland.", "content": "Rats, pretreated with thyroxine for 2 days, were given one or two iv injections of 500 mU of TSH; in some groups the second TSH dose was replaced by 0.75 micronmol isoproternol. The effects of the thyroid stimulators on the following parameters were studied: the number of exocytotic vesicles in the follicle cells; the incorporation of 125I into thyroid proteins, measured over periods of 5 min; and the thyroidal cAMP contents. At 2 h after TSH administration, a second dose of TSH failed to stimulate iodination while at 8 h the iodination response was \"normal\". Two hours after TSH the follicle cells contained practically no exocytotic vesicles but at 8 h they had a full supply of vesicles, and this was emptied by the second TSH injection. THE CAMP content was less increased by the second TSH injection than by the first one, but the stimulatory effect of the second TSH dose on cAMP was the same at 2 h and at 8 h; this indicates that the lack of iodination response at 2 h was not simply due to blocking of TSH receptors. Isoproternol, which acts on other receptors than does TSH, cause a similar cAMP increase incontrols and at 2 h and 8 h after TSH, but stimulated iodination only in controls and at 8 h after TSH; this supported the conclusion that the lack of iodination response to a second TSH dose at 2 h was not due to impairment of the adenylate cyclase-cAMP system. These observations taken together strongly indicate that a rapid iodination response to TSH depends on stimulated exocytosis which, in turn, requires a pool of exocytotic vesicles in the follicle cells. Such a coupling between exocytosis and iodination seems appropriate since by exocytosis uniodinated thyroglobulin and membrane, showing peroxidase activity histochemically, are delivered to the site of iodination, the apical cell surface.", "contents": "Effects of thyrotropin on thyroglobulin exocytosis and iodination in the rat thyroid gland. Rats, pretreated with thyroxine for 2 days, were given one or two iv injections of 500 mU of TSH; in some groups the second TSH dose was replaced by 0.75 micronmol isoproternol. The effects of the thyroid stimulators on the following parameters were studied: the number of exocytotic vesicles in the follicle cells; the incorporation of 125I into thyroid proteins, measured over periods of 5 min; and the thyroidal cAMP contents. At 2 h after TSH administration, a second dose of TSH failed to stimulate iodination while at 8 h the iodination response was \"normal\". Two hours after TSH the follicle cells contained practically no exocytotic vesicles but at 8 h they had a full supply of vesicles, and this was emptied by the second TSH injection. THE CAMP content was less increased by the second TSH injection than by the first one, but the stimulatory effect of the second TSH dose on cAMP was the same at 2 h and at 8 h; this indicates that the lack of iodination response at 2 h was not simply due to blocking of TSH receptors. Isoproternol, which acts on other receptors than does TSH, cause a similar cAMP increase incontrols and at 2 h and 8 h after TSH, but stimulated iodination only in controls and at 8 h after TSH; this supported the conclusion that the lack of iodination response to a second TSH dose at 2 h was not due to impairment of the adenylate cyclase-cAMP system. These observations taken together strongly indicate that a rapid iodination response to TSH depends on stimulated exocytosis which, in turn, requires a pool of exocytotic vesicles in the follicle cells. Such a coupling between exocytosis and iodination seems appropriate since by exocytosis uniodinated thyroglobulin and membrane, showing peroxidase activity histochemically, are delivered to the site of iodination, the apical cell surface."}
{"id": "PMID:217594", "title": "Enriched populations of rat pituitary thyrotrophs in monolayer culture.", "content": "Rat anterior pituitary cells were dissociated and subjected to 4 h of unit gravity sedimentation. Eighty-five 8-ml fractions were collected, and nine pooled fractions were placed in monolayer culture for 1 week. The attached cells were immunocytochemically stained for TSH using an antiserum previously shown to be specific for the beta subunit of TSH and all culture media saved for subsequent assay of TSH. Thyrotrophs were localized both immunocytochemically and by radioimmunoassay to 1-2 fractions from the top of the sedimentation chamber. Typically, it was found that 60-80% of the cells in these fractions were immunocytochemically identified as thyrotrophs. Electron microscopic observations indicated that such cells displayed the classical morphological features associated with thyrotrophs. The enriched thyrotroph cultures responded to 1.0 mM dibutyryl cyclic AMP with an increased release of TSH indicating that the intracellular secretory machinery was not altered by the procedures employed. In all cases, the basal TSH secretion decreased with time in culture. In addition, the fractions containing the most TSH in the culture media were usually one fraction lighter (lower sedimentation rate) than the fractions which were found immunocytochemically to contain the highest percentage of thyrotrophs. The results suggest the possibility of two functionally distinct thyrotroph cell types as has been suggested for the pituitary somatotrophs.", "contents": "Enriched populations of rat pituitary thyrotrophs in monolayer culture. Rat anterior pituitary cells were dissociated and subjected to 4 h of unit gravity sedimentation. Eighty-five 8-ml fractions were collected, and nine pooled fractions were placed in monolayer culture for 1 week. The attached cells were immunocytochemically stained for TSH using an antiserum previously shown to be specific for the beta subunit of TSH and all culture media saved for subsequent assay of TSH. Thyrotrophs were localized both immunocytochemically and by radioimmunoassay to 1-2 fractions from the top of the sedimentation chamber. Typically, it was found that 60-80% of the cells in these fractions were immunocytochemically identified as thyrotrophs. Electron microscopic observations indicated that such cells displayed the classical morphological features associated with thyrotrophs. The enriched thyrotroph cultures responded to 1.0 mM dibutyryl cyclic AMP with an increased release of TSH indicating that the intracellular secretory machinery was not altered by the procedures employed. In all cases, the basal TSH secretion decreased with time in culture. In addition, the fractions containing the most TSH in the culture media were usually one fraction lighter (lower sedimentation rate) than the fractions which were found immunocytochemically to contain the highest percentage of thyrotrophs. The results suggest the possibility of two functionally distinct thyrotroph cell types as has been suggested for the pituitary somatotrophs."}
{"id": "PMID:217595", "title": "Uncoupling by cooling of secretion and adenosine 3',5'-monophosphate accumulation in stimulated dog thyroid slices.", "content": "Thyroid metabolism undergoes general activation in the presence of TSH. Secretion, [1-14C]-glucose oxidation, protein iodination, and cyclic AMP (cAMP) accumulation are stimulated. In intact tissue, it is difficult to dissociate effects of cAMP itself and effects secondary to cAMP-induced secretion. We report herein that cooling to 20 C dissociates the action of TSH on secretion from all its other effects. At this temperature, TSH stimulation of secretion was completely inhibited whereas cAMP accumulation was enhanced. The TSH effect on [1-14C]glucose oxidation was maintained and its action on protein iodination was diminished but not abolished. The ATP content was not decreased. The mechanism of action of cooling was investigated. No pseudopod formation of intracellular colloid droplets were observed by scanning electron microscopy and transmission electron microscopy, thus indicating that the inhibition affects the first step of secretion, i.e., colloid phagocytosis. Microtubules were not seen at 2 C but were normally present at 20 C. The data are compatible with the hypothesis that inhibition of phagocytosis at 20 C could be a consequence of a lipid phase transition in the membrane.", "contents": "Uncoupling by cooling of secretion and adenosine 3',5'-monophosphate accumulation in stimulated dog thyroid slices. Thyroid metabolism undergoes general activation in the presence of TSH. Secretion, [1-14C]-glucose oxidation, protein iodination, and cyclic AMP (cAMP) accumulation are stimulated. In intact tissue, it is difficult to dissociate effects of cAMP itself and effects secondary to cAMP-induced secretion. We report herein that cooling to 20 C dissociates the action of TSH on secretion from all its other effects. At this temperature, TSH stimulation of secretion was completely inhibited whereas cAMP accumulation was enhanced. The TSH effect on [1-14C]glucose oxidation was maintained and its action on protein iodination was diminished but not abolished. The ATP content was not decreased. The mechanism of action of cooling was investigated. No pseudopod formation of intracellular colloid droplets were observed by scanning electron microscopy and transmission electron microscopy, thus indicating that the inhibition affects the first step of secretion, i.e., colloid phagocytosis. Microtubules were not seen at 2 C but were normally present at 20 C. The data are compatible with the hypothesis that inhibition of phagocytosis at 20 C could be a consequence of a lipid phase transition in the membrane."}
{"id": "PMID:217598", "title": "Angiotensin II receptors and aldosterone production in rat adrenal glomerulosa cells.", "content": "Specific receptors for angiotensin II (A II) were demonstrated in membrane fractions and collagenase-dispersed cells from the zona glomerulosa of the rat adrenal gland. The equilibrium association constant (Ka) of the A II binding sites was similar in particulate fractions (2.0 +/- 0.4 (SE) X 10(9) M-1) and intact glomerulosa cells (1.8 +/- 0.3 X 10(9) M-1). Specific binding of [125I]iodo-A II was enhanced by increasing sodium concentration, and in the presence of dithiothreitol, EDTA, and EGTA. Plasma membrane fractions prepared by density gradient centrifugation showed increased binding of [125I]iodo-A II, and were correspondingly enriched in adenylate cyclase and sodium-potassium-dependent ATPase. Steroid production by collagenase-dispersed adrenal glomerulosa cells was highly responsive to A II and ACTH. Significant increases in aldosterone and corticosterone production were elicited by A II concentrations as low as 3 X 10(-11) M, equivalent to normal blood levels of A II in rats (5 X 10(-11) M). The maximum increase in aldosterone production, of 6--7 times the basal value, was obtained at 10(-9) M A II. Dispersed capsular cells were also highly sensitive to ACTH, responding to concentrations down to 3 X 10(-12) M with increased aldosterone production, reaching a maximum aldosterone response of 20-fold above the basal value. The magnitudes of the aldosterone and corticosterone responses to A II in capsular and fasciculata-reticularis cells were commensurate with the distribution of A II receptors, which were 11-fold more concentrated in capsular cells. The ability of A II to evoke aldosterone production at physiological concentrations, and the correspondence between A II binding and steroidogenesis in capsular cells, demonstrate the functional importance of A II receptor sites in the zona glomerulosa of the rat adrenal cortex.", "contents": "Angiotensin II receptors and aldosterone production in rat adrenal glomerulosa cells. Specific receptors for angiotensin II (A II) were demonstrated in membrane fractions and collagenase-dispersed cells from the zona glomerulosa of the rat adrenal gland. The equilibrium association constant (Ka) of the A II binding sites was similar in particulate fractions (2.0 +/- 0.4 (SE) X 10(9) M-1) and intact glomerulosa cells (1.8 +/- 0.3 X 10(9) M-1). Specific binding of [125I]iodo-A II was enhanced by increasing sodium concentration, and in the presence of dithiothreitol, EDTA, and EGTA. Plasma membrane fractions prepared by density gradient centrifugation showed increased binding of [125I]iodo-A II, and were correspondingly enriched in adenylate cyclase and sodium-potassium-dependent ATPase. Steroid production by collagenase-dispersed adrenal glomerulosa cells was highly responsive to A II and ACTH. Significant increases in aldosterone and corticosterone production were elicited by A II concentrations as low as 3 X 10(-11) M, equivalent to normal blood levels of A II in rats (5 X 10(-11) M). The maximum increase in aldosterone production, of 6--7 times the basal value, was obtained at 10(-9) M A II. Dispersed capsular cells were also highly sensitive to ACTH, responding to concentrations down to 3 X 10(-12) M with increased aldosterone production, reaching a maximum aldosterone response of 20-fold above the basal value. The magnitudes of the aldosterone and corticosterone responses to A II in capsular and fasciculata-reticularis cells were commensurate with the distribution of A II receptors, which were 11-fold more concentrated in capsular cells. The ability of A II to evoke aldosterone production at physiological concentrations, and the correspondence between A II binding and steroidogenesis in capsular cells, demonstrate the functional importance of A II receptor sites in the zona glomerulosa of the rat adrenal cortex."}
{"id": "PMID:217599", "title": "Effects of a thyroid hormone analog on fetal rat hepatocyte ultrastructure and microsomal function.", "content": "The effects of an analog of thyroxine, 3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT), on fetal rat hepatocyte ultrastructure and microsomal function were investigated by using the techniques of quantitative electron microscopy and enzyme assays. Rats were injected with DIMIT (10 microgram/100 g BW) or vehicle daily from the 15th through the 19th day of pregnancy. Fetuses were sacrificed on the 20th day of gestation. In comparison with controls, DIMIT-treated livers 1) were devoid of glycogen; 2) contained smaller hepatocytes; 3) contained a greater number of hepatocytes; 4) had an increased volume density of mitochondria; and 5) had increased NADPH-cytochrome c reductase and glucose-6-phosphatase activities. Surface areas of rough and smooth surfaced endoplasmic reticulum were unaffected by the hormone analog, and cytochrome P-450 was not induced. All of the changes that were produced by DIMIT in the 20-day-old fetal rat, as well as smooth endoplasmic reticulum and cytochrome P-450 development, are observed in normal animals within the first 3 days after birth. The data suggest that thyroid hormone may be a physiological stimulus for certain aspects of early hepatic development, but that it acts in combination or in sequence with other factor(s) to produce the full complement of structural and functional changes that occur perinatally in the rat.", "contents": "Effects of a thyroid hormone analog on fetal rat hepatocyte ultrastructure and microsomal function. The effects of an analog of thyroxine, 3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT), on fetal rat hepatocyte ultrastructure and microsomal function were investigated by using the techniques of quantitative electron microscopy and enzyme assays. Rats were injected with DIMIT (10 microgram/100 g BW) or vehicle daily from the 15th through the 19th day of pregnancy. Fetuses were sacrificed on the 20th day of gestation. In comparison with controls, DIMIT-treated livers 1) were devoid of glycogen; 2) contained smaller hepatocytes; 3) contained a greater number of hepatocytes; 4) had an increased volume density of mitochondria; and 5) had increased NADPH-cytochrome c reductase and glucose-6-phosphatase activities. Surface areas of rough and smooth surfaced endoplasmic reticulum were unaffected by the hormone analog, and cytochrome P-450 was not induced. All of the changes that were produced by DIMIT in the 20-day-old fetal rat, as well as smooth endoplasmic reticulum and cytochrome P-450 development, are observed in normal animals within the first 3 days after birth. The data suggest that thyroid hormone may be a physiological stimulus for certain aspects of early hepatic development, but that it acts in combination or in sequence with other factor(s) to produce the full complement of structural and functional changes that occur perinatally in the rat."}
{"id": "PMID:217603", "title": "Tetanus toxin interactions with the thyroid: decreased toxin binding to membranes from a thyroid tumor with a thyrotropin receptor defect and in vivo stimulation of thyroid function.", "content": "Normal rat thyroid membranes adsorb neurotoxicity when incubated with purified tetanus toxin. Membranes from a rat thyroid tumor with a thyrotropin receptor defect adsorb very little neurotoxicity when similarly evaluated. This inability of the tumor membranes to adsorb neurotoxicity is correlated with a defect in their ability to bind both 125I-labeled tetanus toxin and [125I]iodothyrotropin. The effect of tetanus toxin on the release of radioiodine from the thyroids of appropriately prepared mice has been measured by adapting methods used for the bioassay of thyrotropin. One minimum lethal dose of tetanus toxin given sc caused a significant release of radioiodine into the blood of mice 48 h after injection. In mice subjected to the stress of prior bleedings or anesthesia, the release of radioiodine from the thyroid by tetanus toxin was accelerated, i.e., the increase in blood radioiodine could be measured 24 h after injection. These results again suggest that tetanus toxin may interact with thyrotropin receptors on thyroid plasma membranes. The \"sympathetic overactivity syndrome\" seen in some patients with tetanus and the syndrome characterized as \"thyroid storm\" in patients with Graves' disease are discussed as they may relate to these observations.", "contents": "Tetanus toxin interactions with the thyroid: decreased toxin binding to membranes from a thyroid tumor with a thyrotropin receptor defect and in vivo stimulation of thyroid function. Normal rat thyroid membranes adsorb neurotoxicity when incubated with purified tetanus toxin. Membranes from a rat thyroid tumor with a thyrotropin receptor defect adsorb very little neurotoxicity when similarly evaluated. This inability of the tumor membranes to adsorb neurotoxicity is correlated with a defect in their ability to bind both 125I-labeled tetanus toxin and [125I]iodothyrotropin. The effect of tetanus toxin on the release of radioiodine from the thyroids of appropriately prepared mice has been measured by adapting methods used for the bioassay of thyrotropin. One minimum lethal dose of tetanus toxin given sc caused a significant release of radioiodine into the blood of mice 48 h after injection. In mice subjected to the stress of prior bleedings or anesthesia, the release of radioiodine from the thyroid by tetanus toxin was accelerated, i.e., the increase in blood radioiodine could be measured 24 h after injection. These results again suggest that tetanus toxin may interact with thyrotropin receptors on thyroid plasma membranes. The \"sympathetic overactivity syndrome\" seen in some patients with tetanus and the syndrome characterized as \"thyroid storm\" in patients with Graves' disease are discussed as they may relate to these observations."}
{"id": "PMID:217606", "title": "Impaired inner medullary production of prostaglandin E2 in the kidney of the myxedematous rat.", "content": "Renal cAMP concentration and renal prostaglandin (PG) E2 and PGF2alpha production were determined in control rats and rats with surgically induced myxedema. Slices from the kidneys of each group were incubated in vitro. cAMP concentration of inner medullary slices from the kidneys of myxedematous rats was decreased in comparison to slices from control rats. There was no difference between the two groups when slices from outer medulla and cortex were compared for cAMP level. In myxedema, there was decreased inner medullary production of PGE2, but not PGF2alpha. The difference in PGE2 production between myxedema and control rat kidneys was not corrected by addition of either arachidonic acid (170 micronM) or phospholipase A2 (5 microgram/ml). Arachidonic acid, however, increased inner medullary cAMP concentration in myxedema kidneys to a value not measurably different from control. Thus, there appears to be a decreased PGE2 production in the renal inner medulla of rats with myxedema. In view of the fact that PGE2 has previously been shown to increase inner medullary cAMP content, the reduced inner medullary content of cAMP would appear to be attributable to reduced PGE2 production.", "contents": "Impaired inner medullary production of prostaglandin E2 in the kidney of the myxedematous rat. Renal cAMP concentration and renal prostaglandin (PG) E2 and PGF2alpha production were determined in control rats and rats with surgically induced myxedema. Slices from the kidneys of each group were incubated in vitro. cAMP concentration of inner medullary slices from the kidneys of myxedematous rats was decreased in comparison to slices from control rats. There was no difference between the two groups when slices from outer medulla and cortex were compared for cAMP level. In myxedema, there was decreased inner medullary production of PGE2, but not PGF2alpha. The difference in PGE2 production between myxedema and control rat kidneys was not corrected by addition of either arachidonic acid (170 micronM) or phospholipase A2 (5 microgram/ml). Arachidonic acid, however, increased inner medullary cAMP concentration in myxedema kidneys to a value not measurably different from control. Thus, there appears to be a decreased PGE2 production in the renal inner medulla of rats with myxedema. In view of the fact that PGE2 has previously been shown to increase inner medullary cAMP content, the reduced inner medullary content of cAMP would appear to be attributable to reduced PGE2 production."}
{"id": "PMID:217607", "title": "Effects of thyrotropin on iodine metabolism of dog thyroid cells in tissue culture.", "content": "When grown in the presence of thyrotropin, dog thyroid cells in culture from follicle-like structures, take up labeled iodide, and iodinate macromolecular components in the cell. When grown in the absence of thyrotropin, dog thyroid cells in culture form a monolayer, take up only 6% of the iodide of follicular cells, and do not iodinate macromolelcular components in the cell. The iodide uptake in monolayer cells does, however, reflect an incorporation process unique to thyroid cells because hepatocytes and fibroblasts do not have the capacity of the monolayer cells to take up iodide. Thyrotropin stimulation of monolayer cells for a prolonged period (3-8 days) causes the cAMP levels of these cells to return to levels identical to those in follicular cells. The increased cAMP levels are not due to the induction of an adenylate cyclase enzyme, because homogenates of monolayer cells have a thyrotropin-stimulable adenylate cyclase activity. The low level of cAMP, thus, seems to be a problem of receptor coupling to the adenylate cyclase enzyme. The return of cAMP to normal levels is accompanied by an increase in iodide uptake and by macromolecular organification; the return of cAMP levels to normal values is not accompanied by follicular development. The majority (75%) of the iodinated macromolecular product accumulated by follicular thyroid cells, by monolayer thyroid cells stimulated with thyrotropin for a prolonged period, or by thyroid cells treated with dibutyryl cAMP from the onset of culture has the characteristics of 19 S thyroglobulin. The remainder appears to be low mol wt material which may be thyroglobulin-related i.e., be either precursor or biodegraded material.", "contents": "Effects of thyrotropin on iodine metabolism of dog thyroid cells in tissue culture. When grown in the presence of thyrotropin, dog thyroid cells in culture from follicle-like structures, take up labeled iodide, and iodinate macromolecular components in the cell. When grown in the absence of thyrotropin, dog thyroid cells in culture form a monolayer, take up only 6% of the iodide of follicular cells, and do not iodinate macromolelcular components in the cell. The iodide uptake in monolayer cells does, however, reflect an incorporation process unique to thyroid cells because hepatocytes and fibroblasts do not have the capacity of the monolayer cells to take up iodide. Thyrotropin stimulation of monolayer cells for a prolonged period (3-8 days) causes the cAMP levels of these cells to return to levels identical to those in follicular cells. The increased cAMP levels are not due to the induction of an adenylate cyclase enzyme, because homogenates of monolayer cells have a thyrotropin-stimulable adenylate cyclase activity. The low level of cAMP, thus, seems to be a problem of receptor coupling to the adenylate cyclase enzyme. The return of cAMP to normal levels is accompanied by an increase in iodide uptake and by macromolecular organification; the return of cAMP levels to normal values is not accompanied by follicular development. The majority (75%) of the iodinated macromolecular product accumulated by follicular thyroid cells, by monolayer thyroid cells stimulated with thyrotropin for a prolonged period, or by thyroid cells treated with dibutyryl cAMP from the onset of culture has the characteristics of 19 S thyroglobulin. The remainder appears to be low mol wt material which may be thyroglobulin-related i.e., be either precursor or biodegraded material."}
{"id": "PMID:217609", "title": "Characterization of adult bovine adrenocortical cells throughout their life span in tissue culture.", "content": "The characteristics of adult bovine adrenocortical cells were studied throughout their life span of 55-65 generations in monolayer culture. Over this period, the cells maintained the capacity to synthesize steroids when tested with repeated maximal doses of ACTH, prostaglandin E1, monobutyryl cAMP, or cholera toxin. Prostaglandin E1 stimulated cAMP production and steroidogenesis, and inhibited DNA synthesis, as measured by incorporation of [3H]thymidine, with dose-response characteristics that did not vary over the first 50 generations in culture. In contrast, the maximal rate of cAMP production stimulated by ACTH declined exponentially at a rate of 7% per generation. In primary and secondary cultures, ACTH stimulated steroidogenesis maximally and inhibited [3H]thymidine incorporation into DNA completely at a half-maximal effective concentration (ED50) of 0.08 nM which was two orders of magnitude less than the ED50 of 8 nM for stimulation of cAMP production. As the ACTH-stimulated maximal rate of cAMP production fell with increasing generation number, the ED50 for ACTH stimulation of steroidogenesis and inhibition of DNA synthesis increased. From about the 20th generation onward, the ability of ACTH to inhibit DNA synthesis maximally declined so that by the 40th generation, cells were completely resistant to the growth-inhibitory effects of ACTH. High-dose ACTH continued, however, to stimulate steroid production maximally over the 50 generations studied. In late passage cells, the ED50 for ACTH stimulation of steroidogenesis was 8 nM, identical to that for cAMP production. Although ACTH-stimulated cAMP production was related to both stimulation of steroidogenesis and inhibition of DNA synthesis, higher cAMP levels appeared required for inhibition of DNA synthesis than for stimulation of steroidogenesis. Mitogenic responses to fibroblast growth factor and to angiotensin II were retained throughout long term growth in culture. The progressive loss of ACTH-responsiveness was specific and a function of aging of bovine adrenocortical cells in culture.", "contents": "Characterization of adult bovine adrenocortical cells throughout their life span in tissue culture. The characteristics of adult bovine adrenocortical cells were studied throughout their life span of 55-65 generations in monolayer culture. Over this period, the cells maintained the capacity to synthesize steroids when tested with repeated maximal doses of ACTH, prostaglandin E1, monobutyryl cAMP, or cholera toxin. Prostaglandin E1 stimulated cAMP production and steroidogenesis, and inhibited DNA synthesis, as measured by incorporation of [3H]thymidine, with dose-response characteristics that did not vary over the first 50 generations in culture. In contrast, the maximal rate of cAMP production stimulated by ACTH declined exponentially at a rate of 7% per generation. In primary and secondary cultures, ACTH stimulated steroidogenesis maximally and inhibited [3H]thymidine incorporation into DNA completely at a half-maximal effective concentration (ED50) of 0.08 nM which was two orders of magnitude less than the ED50 of 8 nM for stimulation of cAMP production. As the ACTH-stimulated maximal rate of cAMP production fell with increasing generation number, the ED50 for ACTH stimulation of steroidogenesis and inhibition of DNA synthesis increased. From about the 20th generation onward, the ability of ACTH to inhibit DNA synthesis maximally declined so that by the 40th generation, cells were completely resistant to the growth-inhibitory effects of ACTH. High-dose ACTH continued, however, to stimulate steroid production maximally over the 50 generations studied. In late passage cells, the ED50 for ACTH stimulation of steroidogenesis was 8 nM, identical to that for cAMP production. Although ACTH-stimulated cAMP production was related to both stimulation of steroidogenesis and inhibition of DNA synthesis, higher cAMP levels appeared required for inhibition of DNA synthesis than for stimulation of steroidogenesis. Mitogenic responses to fibroblast growth factor and to angiotensin II were retained throughout long term growth in culture. The progressive loss of ACTH-responsiveness was specific and a function of aging of bovine adrenocortical cells in culture."}
{"id": "PMID:217610", "title": "Independence of steroidogenic capacity and luteinizing hormone receptor induction in developing granulosa cells.", "content": "The relationship between FSH-induced acquisition of LH/hCG receptors and the steroidogenic capacity of granulosa cells from estrogen-primed hypophysectomized rat ovaries has been examined. Granulosa cells harvested from the immature preantral follicles of animals not treated with FSH (controls) displayed negligible specific human [125I]iodo-hCG binding and produced only minimal amounts of progesterone during 48 h of culture in vitro. Addition of highly purified hFSH or prostaglandin-E2 (PGE2) to the culture medium elicited substantial increases in progesterone production which were not accompanied by measurable increases in [125I]iodo-hCG binding. Treatment with oFSH in vivo for 24 h led to the initiation of antrum formation in many follicles and was accompanied by an 8-10-fold increase in hCG binding by freshly isolated granulosa cells. Basal, hFSH-, and PGE2-stimulated progesterone production during culture was also greater than controls. In contrast, cells from animals receiving oFSH in vivo for only 12 h showed no increase in hCG binding either before or after culture, yet basal and stimulated progesterone production in vitro was significantly greater than controls, indicating that the initiation of steroidogenesis was antecedent to LH/hCG receptor induction. Only those cells obtained after the 24-h in vivo treatment with oFSH produced elevated amounts of progesterone when incubated in the presence of hCG, thereby showing that the observed increases in [125I]iodo-hCG binding reflected the induction of functionally active LH/hCG receptors. Pharmacological stimulation of steroidogenesis by cell suspensions with N,O'-dibutyryl cAMP resulted in consistently high levels of progesterone production irrespective of previous treatment with FSH in vivo. This uniform expression of in vitro steroidogenic capacity occurred in the complete absence of measurable increases in LH/hCG receptors, suggesting that these two fundamental developmental processes are independent phenomena which may be under separate regulation in vivo.", "contents": "Independence of steroidogenic capacity and luteinizing hormone receptor induction in developing granulosa cells. The relationship between FSH-induced acquisition of LH/hCG receptors and the steroidogenic capacity of granulosa cells from estrogen-primed hypophysectomized rat ovaries has been examined. Granulosa cells harvested from the immature preantral follicles of animals not treated with FSH (controls) displayed negligible specific human [125I]iodo-hCG binding and produced only minimal amounts of progesterone during 48 h of culture in vitro. Addition of highly purified hFSH or prostaglandin-E2 (PGE2) to the culture medium elicited substantial increases in progesterone production which were not accompanied by measurable increases in [125I]iodo-hCG binding. Treatment with oFSH in vivo for 24 h led to the initiation of antrum formation in many follicles and was accompanied by an 8-10-fold increase in hCG binding by freshly isolated granulosa cells. Basal, hFSH-, and PGE2-stimulated progesterone production during culture was also greater than controls. In contrast, cells from animals receiving oFSH in vivo for only 12 h showed no increase in hCG binding either before or after culture, yet basal and stimulated progesterone production in vitro was significantly greater than controls, indicating that the initiation of steroidogenesis was antecedent to LH/hCG receptor induction. Only those cells obtained after the 24-h in vivo treatment with oFSH produced elevated amounts of progesterone when incubated in the presence of hCG, thereby showing that the observed increases in [125I]iodo-hCG binding reflected the induction of functionally active LH/hCG receptors. Pharmacological stimulation of steroidogenesis by cell suspensions with N,O'-dibutyryl cAMP resulted in consistently high levels of progesterone production irrespective of previous treatment with FSH in vivo. This uniform expression of in vitro steroidogenic capacity occurred in the complete absence of measurable increases in LH/hCG receptors, suggesting that these two fundamental developmental processes are independent phenomena which may be under separate regulation in vivo."}
{"id": "PMID:217611", "title": "Evidence that the hypothalamus mediates endotoxin stimulation of adrenocorticotropic hormone secretion.", "content": "The site of action of Escherichia coli endotoxin in inducing ACTH secretion was studied in vivo and in vitro. Hypophysectomized rats, bearing two to three transplanted pituitaries under the kidney capsule and \"primed\" with exogenous ACTH, responded to 2.0-7.5 microgram/100 g BW ip or iv endotoxin with a several-fold increase of plasma corticosterone. This response was markedly reduced by hypothalamic lesions and completely abolished by removing the entire forebrain. Endotoxin added directly to cultured rat adenohypophyseal cells in a concentration up to 10 microgram/ml did not induce significant ACTH secretion. We conclude that endotoxin-induced ACTH secretion from heterotopically transplanted pituitaries is mediated primarily by the hypothalamus, presumably through hypothalamic CRF that reaches the transplanted pituitaries via the systemic circulation.", "contents": "Evidence that the hypothalamus mediates endotoxin stimulation of adrenocorticotropic hormone secretion. The site of action of Escherichia coli endotoxin in inducing ACTH secretion was studied in vivo and in vitro. Hypophysectomized rats, bearing two to three transplanted pituitaries under the kidney capsule and \"primed\" with exogenous ACTH, responded to 2.0-7.5 microgram/100 g BW ip or iv endotoxin with a several-fold increase of plasma corticosterone. This response was markedly reduced by hypothalamic lesions and completely abolished by removing the entire forebrain. Endotoxin added directly to cultured rat adenohypophyseal cells in a concentration up to 10 microgram/ml did not induce significant ACTH secretion. We conclude that endotoxin-induced ACTH secretion from heterotopically transplanted pituitaries is mediated primarily by the hypothalamus, presumably through hypothalamic CRF that reaches the transplanted pituitaries via the systemic circulation."}
{"id": "PMID:217612", "title": "Decreased Leydig cell responsiveness in the testicular feminized male rat.", "content": "The Stanley-Gumbreck pseudohermaphrodite or testicular feminized male (tfm) rat exhibits a decreased Leydig cell sensitivity to human CG (hCG) measured by androgen and cyclic-3',5',-adenosine monophosphate production in vitro. These changes were associated with an 80% reduction in the number of LH receptors in the tfm testis, when compared on the basis of equivalent amounts of testis particle protein or per 10(6) isolated Leydig cells. Androstenedione and not testosterone is the major androgen secreted by the tfm Leydig cell and androstenedione secretion is, therefore, a more appropriate end point than testosterone secretion for Leydig cell function in tfm animals. A dose of hCG (3 ng/2 ml) which elicited a near maximal response in androgen production from the decapsulated testes and Leydig cell suspensions of normals rats, did not significantly stimulate androgen production from Leydig cells of the tfm animals. A much higher dose of hCG (200 ng/2 ml) gave a response from the tfm Leydig cells which was comparable to that obtained with 3 ng from Leydig cells of normal littermates. This indicates that the small number of LH receptors on the tfm Leydig cell membrane are functional and that the reduction in receptor number results in a decrease in the sensitivity of response to LH rather than a reduction in the maximum steroid response.", "contents": "Decreased Leydig cell responsiveness in the testicular feminized male rat. The Stanley-Gumbreck pseudohermaphrodite or testicular feminized male (tfm) rat exhibits a decreased Leydig cell sensitivity to human CG (hCG) measured by androgen and cyclic-3',5',-adenosine monophosphate production in vitro. These changes were associated with an 80% reduction in the number of LH receptors in the tfm testis, when compared on the basis of equivalent amounts of testis particle protein or per 10(6) isolated Leydig cells. Androstenedione and not testosterone is the major androgen secreted by the tfm Leydig cell and androstenedione secretion is, therefore, a more appropriate end point than testosterone secretion for Leydig cell function in tfm animals. A dose of hCG (3 ng/2 ml) which elicited a near maximal response in androgen production from the decapsulated testes and Leydig cell suspensions of normals rats, did not significantly stimulate androgen production from Leydig cells of the tfm animals. A much higher dose of hCG (200 ng/2 ml) gave a response from the tfm Leydig cells which was comparable to that obtained with 3 ng from Leydig cells of normal littermates. This indicates that the small number of LH receptors on the tfm Leydig cell membrane are functional and that the reduction in receptor number results in a decrease in the sensitivity of response to LH rather than a reduction in the maximum steroid response."}
{"id": "PMID:217613", "title": "Interaction of cyanoketone and other steroid nitriles with cytochrome oxidase, hemoglobin, and cytochrome P-450.", "content": "The inhibitory activity of cyanoketone (CNK; 2alpha-cyano-4,4,17alpha-trimethyl-17beta-hydroxy-5-androsten-3-one), was investigated for enzymes of the respiratory chain and cholesterol side chain cleavage (CSCC). In bovine corpus luteum mitochondria incubated with [26-14C]cholesterol, 500 micron CNK caused 90% inhibition of pregnenolone synthesis. Comparable results were obtained with adrenal and placental mitochondria. Addition of CNK to bovine corpus luteum mitochondria or to cytochrome P-450 purified from this source elicited a concentration-dependent, reverse type I difference spectrum with an absorption maximum at about 423 nm and a minimum at about 395 nm, confirming binding to oxidized cytochrome P-450. This spectral change resembles those of steroids which inhibit CSCC. In mitochondrial preparations, CNK induced a second peak at about 445 nm. This peak was similar to that elicited by the interaction of potassium cyanide with cytochrome a3 when the former is added to rabbit heart mitochondria which are devoid of P-450. Like cyanide, CNK block mitochondrial respiration at the cytochrome oxidase site, and induced spectral changes in human hemoglobin. Therefore, this peak at 445 nm probably represents the interaction of CNK with oxidized cytochrome a3. Several other steroid nitriles had little, if any, effect on CSCC activity, nor did they induce spectral changes with cytochrome oxidase or hemoglobin. It appears that the steroid configuration of CNK is responsible for the binding to P-450 and inhibition of CSCC, whereas the binding to cytochrome a3 and hemoglobin and the inhibitory effect on electron transfer are probably related to the cyano group of CNK.", "contents": "Interaction of cyanoketone and other steroid nitriles with cytochrome oxidase, hemoglobin, and cytochrome P-450. The inhibitory activity of cyanoketone (CNK; 2alpha-cyano-4,4,17alpha-trimethyl-17beta-hydroxy-5-androsten-3-one), was investigated for enzymes of the respiratory chain and cholesterol side chain cleavage (CSCC). In bovine corpus luteum mitochondria incubated with [26-14C]cholesterol, 500 micron CNK caused 90% inhibition of pregnenolone synthesis. Comparable results were obtained with adrenal and placental mitochondria. Addition of CNK to bovine corpus luteum mitochondria or to cytochrome P-450 purified from this source elicited a concentration-dependent, reverse type I difference spectrum with an absorption maximum at about 423 nm and a minimum at about 395 nm, confirming binding to oxidized cytochrome P-450. This spectral change resembles those of steroids which inhibit CSCC. In mitochondrial preparations, CNK induced a second peak at about 445 nm. This peak was similar to that elicited by the interaction of potassium cyanide with cytochrome a3 when the former is added to rabbit heart mitochondria which are devoid of P-450. Like cyanide, CNK block mitochondrial respiration at the cytochrome oxidase site, and induced spectral changes in human hemoglobin. Therefore, this peak at 445 nm probably represents the interaction of CNK with oxidized cytochrome a3. Several other steroid nitriles had little, if any, effect on CSCC activity, nor did they induce spectral changes with cytochrome oxidase or hemoglobin. It appears that the steroid configuration of CNK is responsible for the binding to P-450 and inhibition of CSCC, whereas the binding to cytochrome a3 and hemoglobin and the inhibitory effect on electron transfer are probably related to the cyano group of CNK."}
{"id": "PMID:217614", "title": "Regulation of 18-hydroxydeoxycorticosterone in the rat.", "content": "Simultaneous measurements of plasma 18-hydroxydeoxycorticosterone (18 OH-DOC), corticosterone, and aldosterone were performed in the rat by using RIA. Under basal conditions, 18 OH-DOC levels averaged 11.3 +/- 3.7 (SE) ng/ml. Plasma concentrations were increased 8-fold (86.8 +/- 8.0 ng/ml) 1 h after 1 U sc ACTH. Dexamethasone suppressed 18 OH-DOC to less than 1.5 ng/ml, irrespective of Na+ intake. Neither Na+ depletion nor Na+ loading had any influence on 18 OH-DOC levels. Excellent correlation between 18 OH-DOC and corticosterone (r = 0.90, P less than 0.001) was observed, whereas there was none between 18 OH-DOC and aldosterone (r = 0.061, P greater than 0.6). In the rat, 18 OH-DOC is an ACTH-dependent steroid which does not appear to be under the influence of the renin-angiotensin system.", "contents": "Regulation of 18-hydroxydeoxycorticosterone in the rat. Simultaneous measurements of plasma 18-hydroxydeoxycorticosterone (18 OH-DOC), corticosterone, and aldosterone were performed in the rat by using RIA. Under basal conditions, 18 OH-DOC levels averaged 11.3 +/- 3.7 (SE) ng/ml. Plasma concentrations were increased 8-fold (86.8 +/- 8.0 ng/ml) 1 h after 1 U sc ACTH. Dexamethasone suppressed 18 OH-DOC to less than 1.5 ng/ml, irrespective of Na+ intake. Neither Na+ depletion nor Na+ loading had any influence on 18 OH-DOC levels. Excellent correlation between 18 OH-DOC and corticosterone (r = 0.90, P less than 0.001) was observed, whereas there was none between 18 OH-DOC and aldosterone (r = 0.061, P greater than 0.6). In the rat, 18 OH-DOC is an ACTH-dependent steroid which does not appear to be under the influence of the renin-angiotensin system."}
{"id": "PMID:217615", "title": "Hypothyroidism-induced changes in triiodothyronine binding to nuclei and cytosol-binding proteins in rat liver.", "content": "A tracer dose of [125I]T3 was given iv to normal, thyroidectomized, and propylthiouracil-fed rats and the distribution of radioactivity in serum and liver fractions was studied over 1 h. Total liver homogenate and serum 125I were higher at all times in hypothyroid rats and, in all groups, showed a continuous fall over the period studied. Hepatic nuclear 125I was maximal at 20 min in all and was greater in hypothyroid rats; there was more 125I in the hepatic cytosol of normal rats than in that from either thyroidectomized or propylthiouracil-fed animals. Binding studies with [125I]T3 and purified hepatic neclear preparations in vitro indicated that both the association constant, Ka (1.08-9.0 x 10(9) M-1) and the capacity (500-600 pg/mg DNA) in thyroidectomized and goitrogen-treated rats were similar to those obtained with normal animals. Cytosol, on the other hand, showed a decrease in binding capacity without change in affinity in livers of hypothyroid rats. Analysis of binding data by Hill plots indicated the presence of both positive and negative cooperativity in binding of T3 by rat liver cytosol proteins. In the in vitro experiments, higher serum radioactivity alone could not account for increases in the hepatic nuclear 125I in the hypothyroid rats because cytosol 125I (presumably in dynamic exchange with both blood and nuclei) was less. Consequently, cytosol T3-binding proteins may regulate the free T3 concentration in the cell and, thus influence the distribution of the hormone in other cellular compartments.", "contents": "Hypothyroidism-induced changes in triiodothyronine binding to nuclei and cytosol-binding proteins in rat liver. A tracer dose of [125I]T3 was given iv to normal, thyroidectomized, and propylthiouracil-fed rats and the distribution of radioactivity in serum and liver fractions was studied over 1 h. Total liver homogenate and serum 125I were higher at all times in hypothyroid rats and, in all groups, showed a continuous fall over the period studied. Hepatic nuclear 125I was maximal at 20 min in all and was greater in hypothyroid rats; there was more 125I in the hepatic cytosol of normal rats than in that from either thyroidectomized or propylthiouracil-fed animals. Binding studies with [125I]T3 and purified hepatic neclear preparations in vitro indicated that both the association constant, Ka (1.08-9.0 x 10(9) M-1) and the capacity (500-600 pg/mg DNA) in thyroidectomized and goitrogen-treated rats were similar to those obtained with normal animals. Cytosol, on the other hand, showed a decrease in binding capacity without change in affinity in livers of hypothyroid rats. Analysis of binding data by Hill plots indicated the presence of both positive and negative cooperativity in binding of T3 by rat liver cytosol proteins. In the in vitro experiments, higher serum radioactivity alone could not account for increases in the hepatic nuclear 125I in the hypothyroid rats because cytosol 125I (presumably in dynamic exchange with both blood and nuclei) was less. Consequently, cytosol T3-binding proteins may regulate the free T3 concentration in the cell and, thus influence the distribution of the hormone in other cellular compartments."}
{"id": "PMID:217616", "title": "Inhibitory and facilitatory areas of the ventral midbrain mediating release of corticotropin in the cat.", "content": "To examine the role of the ventral midbrain in the control of release of ACTH, we stimulated electrically 92 sites in the mesencephalon of 15 cats anesthetized with chloralose/urethane. Responses of arterial pressure could not account for change of release of ACTH. Three active areas were identified. First, in a dorsal facilitatory area that includes the dorsal longitudinal fasciculus, electrical stimulation led to changes in ACTH of +106, +117, and +90 pg/ml at 1.5, 3.5,  and 6.5 min, respectively (P less than 0.05). Second, in a more ventral inhibitory area that includes the mammillary peduncle, electrical stimulation led to changes in ACTH of -63, -72, and -47 pg/ml, respectively (P less than 0.05). Third, in a ventral facilitatory area that includes the ventral tegmental area of Tsai, electrical stimulation led to changes in ACTH of +57, +56, and +59 pg/ml, respectively (P less than 0.01). The inhibitory and facilitatory areas of the ventral midbrain appeared to be continuous, respectively, with the inhibitory and facilitatory areas mediating control of ACTH in the dorsal rostral pons and in the hypothalamus. Anatomical evidence indicates projections from these ACTH-active areas of the midbrain and of the pons to ACTH-active areas of the hypothalamus. Thus, the present results suggest that the midbrain areas identified may represent pathways from ACTH-active areas of the pons to the hypothalamus.", "contents": "Inhibitory and facilitatory areas of the ventral midbrain mediating release of corticotropin in the cat. To examine the role of the ventral midbrain in the control of release of ACTH, we stimulated electrically 92 sites in the mesencephalon of 15 cats anesthetized with chloralose/urethane. Responses of arterial pressure could not account for change of release of ACTH. Three active areas were identified. First, in a dorsal facilitatory area that includes the dorsal longitudinal fasciculus, electrical stimulation led to changes in ACTH of +106, +117, and +90 pg/ml at 1.5, 3.5,  and 6.5 min, respectively (P less than 0.05). Second, in a more ventral inhibitory area that includes the mammillary peduncle, electrical stimulation led to changes in ACTH of -63, -72, and -47 pg/ml, respectively (P less than 0.05). Third, in a ventral facilitatory area that includes the ventral tegmental area of Tsai, electrical stimulation led to changes in ACTH of +57, +56, and +59 pg/ml, respectively (P less than 0.01). The inhibitory and facilitatory areas of the ventral midbrain appeared to be continuous, respectively, with the inhibitory and facilitatory areas mediating control of ACTH in the dorsal rostral pons and in the hypothalamus. Anatomical evidence indicates projections from these ACTH-active areas of the midbrain and of the pons to ACTH-active areas of the hypothalamus. Thus, the present results suggest that the midbrain areas identified may represent pathways from ACTH-active areas of the pons to the hypothalamus."}
{"id": "PMID:217617", "title": "Effect of piperoxane on serum prolactin: possible role of epinephrine-mediated synapses in the inhibition of prolactin secretion.", "content": "Intravenous administration of 2,5 mg/kg piperoxane produced a rapid and significant increase in serum PRL concentrations in four non-human primates. This PRL increase was maximal 15 min after piperoxane infusion and significant, when compared with baseline levels, in the +15, +30, +45, +60, and +90-min samples. The iv administration of 5 mg/kg piperoxane also produced a rapid and significant increase, whereas saline 0.5 mg/kg or 1.0 mg/kg, did not change serum PRL levels. The iv administration of 10 microgram/kg clonidine, but not saline, produced a rapid and significant reduction in serum PRL levels. PRL levels were significantly reduced +15, +30, and +60 min after the clonidine infusion. Pretreatment with a bolus of 10 microgram/kg clonidine at -15 min caused a significant attenuation of the piperoxane-induced elevation in serum PRL in two monkeys. These data support the hypothesis that alpha-adrenergic receptors are involved in the inhibition of PRL secretion. These data are compatible with noradrenergic or adrenergic mechanisms which remain to be defined.", "contents": "Effect of piperoxane on serum prolactin: possible role of epinephrine-mediated synapses in the inhibition of prolactin secretion. Intravenous administration of 2,5 mg/kg piperoxane produced a rapid and significant increase in serum PRL concentrations in four non-human primates. This PRL increase was maximal 15 min after piperoxane infusion and significant, when compared with baseline levels, in the +15, +30, +45, +60, and +90-min samples. The iv administration of 5 mg/kg piperoxane also produced a rapid and significant increase, whereas saline 0.5 mg/kg or 1.0 mg/kg, did not change serum PRL levels. The iv administration of 10 microgram/kg clonidine, but not saline, produced a rapid and significant reduction in serum PRL levels. PRL levels were significantly reduced +15, +30, and +60 min after the clonidine infusion. Pretreatment with a bolus of 10 microgram/kg clonidine at -15 min caused a significant attenuation of the piperoxane-induced elevation in serum PRL in two monkeys. These data support the hypothesis that alpha-adrenergic receptors are involved in the inhibition of PRL secretion. These data are compatible with noradrenergic or adrenergic mechanisms which remain to be defined."}
{"id": "PMID:217618", "title": "Membrane receptor function and the loss of glucagon-stimulated adenylate cyclase activity in hepatomas.", "content": "Plasma membranes were prepared from homogenates of two well differentiated hepatomas (Morris rat 7787 and Dalton mouse 9815), two poorly differentiated hepatomas (Morris rat 7288-C and Dalton mouse 129), and normal liver. Adenylate cyclase activity and [125I]iodoglucagon binding were measured in the plasma membrane preparations over a wide range of glucagon concentrations. Nether glucagon-stimulated adenylate cyclase activity nor [125I]iodoglucagon binding could be detected in the poorly differentiated hepatomas. Fluoride and epinephrine stimulated adenylate cyclase activity in all hepatomas. Maximum activity of glucagon-stimulated adenylate cyclase and maximum binding of glucagon in the wall differentiated hepatomas were less than those of normal liver. Plasma membranes from liver and hepatomas were solubilized with Lubrol-PX and, after reducing the concentration of detergent, were incubated with [125I]iodoglucagon and then chromatographed on a column of Bio-Gel A 1,5 m. Two peaks containing both protein and [125I]iodoglucagon were found for normal liver but not for the poorly differentiated hepatomas. Fractions from the Bio-Gel column containing the greatest concentration of protein were also subjected to a binding microassay. Material from the poorly differentiated tumors did not bind glucagon in this system, whereas the solubilized normal liver membranes bound up to 1.4 pmol [125I]iodoglucagon/mg protein. This indicates that there is no detectable glucagon receptor in these undifferentiated tumors.", "contents": "Membrane receptor function and the loss of glucagon-stimulated adenylate cyclase activity in hepatomas. Plasma membranes were prepared from homogenates of two well differentiated hepatomas (Morris rat 7787 and Dalton mouse 9815), two poorly differentiated hepatomas (Morris rat 7288-C and Dalton mouse 129), and normal liver. Adenylate cyclase activity and [125I]iodoglucagon binding were measured in the plasma membrane preparations over a wide range of glucagon concentrations. Nether glucagon-stimulated adenylate cyclase activity nor [125I]iodoglucagon binding could be detected in the poorly differentiated hepatomas. Fluoride and epinephrine stimulated adenylate cyclase activity in all hepatomas. Maximum activity of glucagon-stimulated adenylate cyclase and maximum binding of glucagon in the wall differentiated hepatomas were less than those of normal liver. Plasma membranes from liver and hepatomas were solubilized with Lubrol-PX and, after reducing the concentration of detergent, were incubated with [125I]iodoglucagon and then chromatographed on a column of Bio-Gel A 1,5 m. Two peaks containing both protein and [125I]iodoglucagon were found for normal liver but not for the poorly differentiated hepatomas. Fractions from the Bio-Gel column containing the greatest concentration of protein were also subjected to a binding microassay. Material from the poorly differentiated tumors did not bind glucagon in this system, whereas the solubilized normal liver membranes bound up to 1.4 pmol [125I]iodoglucagon/mg protein. This indicates that there is no detectable glucagon receptor in these undifferentiated tumors."}
{"id": "PMID:217619", "title": "Relaxin-dependent adenosine 6',5'-monophosphate concentration changes in the mouse pubic symphysis.", "content": "The amount of cAMP in the pubic symphyses of estrogen-primed mice increases after injection of the hormone relaxin. This relaxin-induced increase in symphyseal cAMP was observed in immature, mature, and ovariectomized mature mice and could be prevented by prior ip injection of rabbit antibodies to porcine relaxin or by treatment of relaxin with dithiothreitol. The highest level of cAMP was measured 30 min after relaxin injection; the level of measurable cMAP then diminished rapidly. Estrogen-priming of the mice was not a prerequisite for a relaxin-induced response to occur. Relaxin administration did not increase the level of cAMP in a non-target tissue such as liver, nor could an increase in cAMP in the pubic symphysis be elicited by injection of insulin, a protein of similar size and structure, or glucagon, a known stimulator of liver cAMP levels.", "contents": "Relaxin-dependent adenosine 6',5'-monophosphate concentration changes in the mouse pubic symphysis. The amount of cAMP in the pubic symphyses of estrogen-primed mice increases after injection of the hormone relaxin. This relaxin-induced increase in symphyseal cAMP was observed in immature, mature, and ovariectomized mature mice and could be prevented by prior ip injection of rabbit antibodies to porcine relaxin or by treatment of relaxin with dithiothreitol. The highest level of cAMP was measured 30 min after relaxin injection; the level of measurable cMAP then diminished rapidly. Estrogen-priming of the mice was not a prerequisite for a relaxin-induced response to occur. Relaxin administration did not increase the level of cAMP in a non-target tissue such as liver, nor could an increase in cAMP in the pubic symphysis be elicited by injection of insulin, a protein of similar size and structure, or glucagon, a known stimulator of liver cAMP levels."}
{"id": "PMID:217621", "title": "Failure of angiotensin II to inhibit corticotropin-stimulated cortisol secretion.", "content": "In view of the reported inhibitory effect of angiotensin II on cortisol secretion in human subjects, the effect of local angiotensin infusions on steroid secretion maintained by ACTH was examined by using sheep with cervical autotransplanted adrenal glands. During sustained submaximal stimulation by exogenous ACTH (40--80 microunit/min), the addition of local infusions of angiotensin II (1.6--160.0 ng/min) caused increased aldosterone and smaller increments in cortisol secretion in most experients. There was no evidence of inhibition of cortisol secretion by angiotensin. When similar experiments were undertaken during maximum stimulation by ACTH (16.6 mU/min), increments in aldosterone, but not in cortisol secretion, were observed. These studies exclude an acute inhibitory effect of angiotensin on cortisol biosynthesis, at least in ovine adrenal glands, during stimulation by ACTH.", "contents": "Failure of angiotensin II to inhibit corticotropin-stimulated cortisol secretion. In view of the reported inhibitory effect of angiotensin II on cortisol secretion in human subjects, the effect of local angiotensin infusions on steroid secretion maintained by ACTH was examined by using sheep with cervical autotransplanted adrenal glands. During sustained submaximal stimulation by exogenous ACTH (40--80 microunit/min), the addition of local infusions of angiotensin II (1.6--160.0 ng/min) caused increased aldosterone and smaller increments in cortisol secretion in most experients. There was no evidence of inhibition of cortisol secretion by angiotensin. When similar experiments were undertaken during maximum stimulation by ACTH (16.6 mU/min), increments in aldosterone, but not in cortisol secretion, were observed. These studies exclude an acute inhibitory effect of angiotensin on cortisol biosynthesis, at least in ovine adrenal glands, during stimulation by ACTH."}
{"id": "PMID:217623", "title": "The biphasic stimulatory and inhibitory effects of concanavalin A on thyroid activation induced by thyrotropin.", "content": "Concanavalin A (Con A) was tested for its ability to affect thyroid activation induced by TSH in mouse thyroid lobes. Pretreatment of thyroid lobes with Con A at concentrations from 1.55--400 microgram/ml was found to have biphasic stimulatory and inhibitory effects of the TSH-induced accumulation of cAMP and formation of colloid droplets. Low concentrations of Con A potentiated TSH activation of thyroidal formation of cAMP and endocytosis. In contrast, higher concentrations of Con A markedly inhibited these TSH effects. The inhibitory effects observed after preincubation with Con A were abolished by the addition of alpha-methyl-D-glucoside to the incubation medium. A high concentration of Con A also inhibited cAMP formation induced either by prostaglandin E2 or the long-acting thyroid stimulator. However, the basal and TSH-stimulated glucose oxidation in mouse thyroid lobes was not depressed by a high concentration of Con A. Uptake of 125 I-labeled Con A by thyroid tissues increased with time up to 1 h and was directly proportional to tissue weight. These findings suggest that the specific interaction between Con A and its receptors may lead to conformational changes in the structure of the membranes of the thyroid follicular cells which facilitate TSH-induced thyroid hormone secretion via the adenylate cyclase-cAMP system.", "contents": "The biphasic stimulatory and inhibitory effects of concanavalin A on thyroid activation induced by thyrotropin. Concanavalin A (Con A) was tested for its ability to affect thyroid activation induced by TSH in mouse thyroid lobes. Pretreatment of thyroid lobes with Con A at concentrations from 1.55--400 microgram/ml was found to have biphasic stimulatory and inhibitory effects of the TSH-induced accumulation of cAMP and formation of colloid droplets. Low concentrations of Con A potentiated TSH activation of thyroidal formation of cAMP and endocytosis. In contrast, higher concentrations of Con A markedly inhibited these TSH effects. The inhibitory effects observed after preincubation with Con A were abolished by the addition of alpha-methyl-D-glucoside to the incubation medium. A high concentration of Con A also inhibited cAMP formation induced either by prostaglandin E2 or the long-acting thyroid stimulator. However, the basal and TSH-stimulated glucose oxidation in mouse thyroid lobes was not depressed by a high concentration of Con A. Uptake of 125 I-labeled Con A by thyroid tissues increased with time up to 1 h and was directly proportional to tissue weight. These findings suggest that the specific interaction between Con A and its receptors may lead to conformational changes in the structure of the membranes of the thyroid follicular cells which facilitate TSH-induced thyroid hormone secretion via the adenylate cyclase-cAMP system."}
{"id": "PMID:217625", "title": "Granules and Golgi vesicles with differential reactivity to ACTH antiserum in the corticotroph of the rat anterior pituitary.", "content": "Slices of unembedded rat anterior pituitaries, fixed with a periodate-lysine-paraformaldehyde (PLP) fixative, were incubated with guinea pig antiserum to ACTH and stained with a peroxidase-conjugated IgG fraction of anti-guinea pig gamma-globulin serum from rabbits. The fine structure of the stained cells was identical to that of the ACTH-secreting cell, as described by Siperstein and coworkers. Immunoreactive granules were mainly located at the periphery of the cell. Numerous granules of the inner cytoplasm and also the Golgi complex were nonreactive to the antiserum. The differential labeling for granules and Golgi apparatus peptide.", "contents": "Granules and Golgi vesicles with differential reactivity to ACTH antiserum in the corticotroph of the rat anterior pituitary. Slices of unembedded rat anterior pituitaries, fixed with a periodate-lysine-paraformaldehyde (PLP) fixative, were incubated with guinea pig antiserum to ACTH and stained with a peroxidase-conjugated IgG fraction of anti-guinea pig gamma-globulin serum from rabbits. The fine structure of the stained cells was identical to that of the ACTH-secreting cell, as described by Siperstein and coworkers. Immunoreactive granules were mainly located at the periphery of the cell. Numerous granules of the inner cytoplasm and also the Golgi complex were nonreactive to the antiserum. The differential labeling for granules and Golgi apparatus peptide."}
{"id": "PMID:217627", "title": "Parathyroid hormone stimulation of adenylate cyclase activity and lactic acid accumulation in calvaria of osteopetrotic (ia) rats.", "content": "We have examined the effect of parathyroid hormone (PTH) on the adenylate cyclase activity of newborn osteopetrotic rat calvaria, to study a possible molecular basis for the reduced response of this mutant to PTH. Phenotypically normal littermates served as controls. We also measured the effect of PTH on kidney adenylate cyclase activity and on lactic acid accumulation in short term cultures of calvaria. PTH stimulated calvarial adenylate cyclase activity in a dose-dependent manner in both mutant rats and normal littermates. Lactic acid production was also enhanced by PTH, and no significant difference between mutants and normal littermates was observed. These findings indicate that the reduced response of the young osteopetrotic rats to PTH is not due to an absence of PTH receptors coupled to adenylate cyclase.", "contents": "Parathyroid hormone stimulation of adenylate cyclase activity and lactic acid accumulation in calvaria of osteopetrotic (ia) rats. We have examined the effect of parathyroid hormone (PTH) on the adenylate cyclase activity of newborn osteopetrotic rat calvaria, to study a possible molecular basis for the reduced response of this mutant to PTH. Phenotypically normal littermates served as controls. We also measured the effect of PTH on kidney adenylate cyclase activity and on lactic acid accumulation in short term cultures of calvaria. PTH stimulated calvarial adenylate cyclase activity in a dose-dependent manner in both mutant rats and normal littermates. Lactic acid production was also enhanced by PTH, and no significant difference between mutants and normal littermates was observed. These findings indicate that the reduced response of the young osteopetrotic rats to PTH is not due to an absence of PTH receptors coupled to adenylate cyclase."}
{"id": "PMID:217630", "title": "Triiodothyronine receptors in rat lung.", "content": "Specific triiodothyronine receptor activity has been detected in rat lung nuclei isolated by Triton X-100, which was sensitive to pH and exhibited temperature-dependent association kinetics. This activity represented a single order of high affinity binding sites, with an apparent dissociation constant for 3,3',5-triiodo-L-thyronine (L-T3) of 0.254 +/- 0.027 nM and an apparent capacity of 249.4 +/- 15.5 fmol 3,3',5-triiodo-L-thyronine/mg DNA. Its specificity was such that triiodothyronine derivatives were bound at least 10 times more avidly than were the tetraiodothyronines. The presence of specific triiodothyronine receptors in lung nuclei suggests that the effect of thyroid hormones on pulmonary surfactant metabolism may be mediated through these binding sites.", "contents": "Triiodothyronine receptors in rat lung. Specific triiodothyronine receptor activity has been detected in rat lung nuclei isolated by Triton X-100, which was sensitive to pH and exhibited temperature-dependent association kinetics. This activity represented a single order of high affinity binding sites, with an apparent dissociation constant for 3,3',5-triiodo-L-thyronine (L-T3) of 0.254 +/- 0.027 nM and an apparent capacity of 249.4 +/- 15.5 fmol 3,3',5-triiodo-L-thyronine/mg DNA. Its specificity was such that triiodothyronine derivatives were bound at least 10 times more avidly than were the tetraiodothyronines. The presence of specific triiodothyronine receptors in lung nuclei suggests that the effect of thyroid hormones on pulmonary surfactant metabolism may be mediated through these binding sites."}
{"id": "PMID:217631", "title": "Glucagon administration decreases hepatic nuclear triiodothyronine binding capacity.", "content": "The maximal binding capacity (MBC) of nuclear triiodothyronine (T3) receptor sites in rat liver decreases markedly after glucagon administration. Administration of serial doses of glucagon (2.5 microgram/100 g BW) resulted in a 33% decrease in MBC in 3.5 h and MBC was reduced by 45% in 6.25 h. The individual doses used were in the same order of magnitude as those used in the treatment of hypoglycemic human subjects (1.5 microgram/100 g BW). This report presents the first evidence that a peptide hormone can change the number of nuclear T3 receptor sites. The physiological significance of these findings remains to be clarified.", "contents": "Glucagon administration decreases hepatic nuclear triiodothyronine binding capacity. The maximal binding capacity (MBC) of nuclear triiodothyronine (T3) receptor sites in rat liver decreases markedly after glucagon administration. Administration of serial doses of glucagon (2.5 microgram/100 g BW) resulted in a 33% decrease in MBC in 3.5 h and MBC was reduced by 45% in 6.25 h. The individual doses used were in the same order of magnitude as those used in the treatment of hypoglycemic human subjects (1.5 microgram/100 g BW). This report presents the first evidence that a peptide hormone can change the number of nuclear T3 receptor sites. The physiological significance of these findings remains to be clarified."}
{"id": "PMID:217632", "title": "In vivo effects of antisera to prolactin receptors in female rats.", "content": "Antisera generated in guinea pigs against partially purified PRL receptors derived from rabbit mammary glands were tested for their effect on PRL binding and the biological effects of PRL in vitro and in vivo. Several dilutions of either normal guinea pig serum or anti-PRL receptor serum were incubated in vitro with homogenates of rat ovaries. Although specific binding of PRL was inhibited as much as 90% by the anti-serum, normal guinea pig serum had little effect. There was no inhibition of binding of LH and FSH to ovaries by these antisera. When these antisera were administered to normal cycling rats, the most pronounced effect was an increase in the number of corpora lutea, presumably due to the prevention of the luteolytic effect of PRL. When one of these antisera was given to adult rats immediately after parturition, weight gain of their pups decreased significantly, possibly reflecting a decrease of milk yield. Thus, passive immunization of animals with anti-PRL receptor sera modifies the actions of PRL on some of its target tissues.", "contents": "In vivo effects of antisera to prolactin receptors in female rats. Antisera generated in guinea pigs against partially purified PRL receptors derived from rabbit mammary glands were tested for their effect on PRL binding and the biological effects of PRL in vitro and in vivo. Several dilutions of either normal guinea pig serum or anti-PRL receptor serum were incubated in vitro with homogenates of rat ovaries. Although specific binding of PRL was inhibited as much as 90% by the anti-serum, normal guinea pig serum had little effect. There was no inhibition of binding of LH and FSH to ovaries by these antisera. When these antisera were administered to normal cycling rats, the most pronounced effect was an increase in the number of corpora lutea, presumably due to the prevention of the luteolytic effect of PRL. When one of these antisera was given to adult rats immediately after parturition, weight gain of their pups decreased significantly, possibly reflecting a decrease of milk yield. Thus, passive immunization of animals with anti-PRL receptor sera modifies the actions of PRL on some of its target tissues."}
{"id": "PMID:217634", "title": "Immunochemical measurement of the vitamin D-binding protein in rat serum.", "content": "The vitamin D-binding protein (DBP) was measured in rat serum using a single radial immunodiffusion technique. Normal serum levels at birth (74 +/- 11 mg/liter, mean +/- SD) were lower than during the last day of fetal life (130 +/- 14 mg/liter) and much lower than in adult rats. A marked sex difference in DBP occurred after puberty: male values (656 +/- 52 mg/liter) were significantly higher than female values (472 +/- 46 mg/liter). The sex difference could be abolished by either adult gonadectomy or transpharyngeal hypophysectomy. Implantation of a pituitary gland under the renal capsule in hypophysectomized male rats further decreased the DBP concentration, suggesting that PRL suppresses the DBP level. A similar decrease was also observed at the end of pregnancy and during lactation. Administration of androgens to either normal female or gonadectomized male rats increased their DBP concentration to the normal adult male level. The serum levels of total 25-hydroxyvitamin D did not fluctuate according to the concentration of DBP, indicating that the concentration of \"free 25-hydroxyvitamin D\" is not regulated at a constant level.", "contents": "Immunochemical measurement of the vitamin D-binding protein in rat serum. The vitamin D-binding protein (DBP) was measured in rat serum using a single radial immunodiffusion technique. Normal serum levels at birth (74 +/- 11 mg/liter, mean +/- SD) were lower than during the last day of fetal life (130 +/- 14 mg/liter) and much lower than in adult rats. A marked sex difference in DBP occurred after puberty: male values (656 +/- 52 mg/liter) were significantly higher than female values (472 +/- 46 mg/liter). The sex difference could be abolished by either adult gonadectomy or transpharyngeal hypophysectomy. Implantation of a pituitary gland under the renal capsule in hypophysectomized male rats further decreased the DBP concentration, suggesting that PRL suppresses the DBP level. A similar decrease was also observed at the end of pregnancy and during lactation. Administration of androgens to either normal female or gonadectomized male rats increased their DBP concentration to the normal adult male level. The serum levels of total 25-hydroxyvitamin D did not fluctuate according to the concentration of DBP, indicating that the concentration of \"free 25-hydroxyvitamin D\" is not regulated at a constant level."}
{"id": "PMID:217636", "title": "Binding of bovine thyrotropin to receptors in rat testis and its interaction with gonadotropins.", "content": "Previously, we have shown that preparations of hCG bind to bovine thyroid membranes, as judged from their ability both to inhibit the binding of 125I-labeled bovine TSH (bTSH) and to activate adenylate cyclase (Amir, S.M., H. Uchimura, and S.H. Ingbar, J Clin Endocrinol Metab 45: 280, 1977). In the present studies, 125I-labeled, highly purified bTSH ([125I]bTSH) has been shown to bind specifically and saturably to receptors in a particulate fraction from rat testis. At 37 C, binding was rapid, reaching a maximum level in less than 15 min, but then declining markedly during the next several hours. At 22 C, binding reached a steady state after 2 h and remained unchanged for another 22 h. Binding of [125I]bTSH was greatest at pH 5.5, at which pH more than 50% of [125I]bTSH was bound in the presence of 330 microgram/ml particulate protein, the concentration of protein that yielded maximum binding. Nevertheless, the majority of experiments were conducted at lesser protein concentrations and at physiological pH (7.45), under which conditions total binding was only 25% of that measured at pH 5.5. Scatchard plots indicated the presence of a single binding site with a dissociation constant of 5.8 X 10(-8) M and a binding capacity of 0.22 nmol/mg protein on the basis of data obtained at 22 C and pH 7.45. Both crude and highly purified preparations of hCG inhibited the binding of [125I]bTSH to testis particulate fraction; crude hCG had 46 times the activity, and purified hCG had only one-tenth the activity of bTSH itself in this respect. This was true despite the fact that with respect to the displacement of [125I]hCG, crude and purified hCG were almost equally active. Bovine LH had one-third the activity of bTSH in displacing [125I]bTSH. Human FSH inhibited [125I]bTSH binding only slightly at the highest concentration tested, while glucagon, insulin, PRL, and GH were inactive. Purified bTSH inhibited the binding of [125I]hCG to testis particulate fraction but contained only about 2% of the activity of purified hCG. Lineweaver-Burk analysis suggested that inhibition of [125I]hCG binding by bTSH was competitive in nature. Purified bTSH stimulated cAMP production in Leydig cells, but with only about 0.1% of the activity of purified hCG. It is concluded that bTSH binds reversibly, saturably, and with relatively high affinity to receptors in rat testis that are either the same as receptors for hCG and LH or that interact therewith. bTSH, like hCG, is capable of stimulating the production of cAMP in rat Leydig cells, but is much less potent than hCG in this regard. Preparations of crude hCG contain a factor lacking hCG activity in bioassay, immunoassay, and receptor assay that is especially potent in displacing [125I]bTSH from receptors in testis, as has earlier been described for bTSH receptors in bovine thyroid membranes.", "contents": "Binding of bovine thyrotropin to receptors in rat testis and its interaction with gonadotropins. Previously, we have shown that preparations of hCG bind to bovine thyroid membranes, as judged from their ability both to inhibit the binding of 125I-labeled bovine TSH (bTSH) and to activate adenylate cyclase (Amir, S.M., H. Uchimura, and S.H. Ingbar, J Clin Endocrinol Metab 45: 280, 1977). In the present studies, 125I-labeled, highly purified bTSH ([125I]bTSH) has been shown to bind specifically and saturably to receptors in a particulate fraction from rat testis. At 37 C, binding was rapid, reaching a maximum level in less than 15 min, but then declining markedly during the next several hours. At 22 C, binding reached a steady state after 2 h and remained unchanged for another 22 h. Binding of [125I]bTSH was greatest at pH 5.5, at which pH more than 50% of [125I]bTSH was bound in the presence of 330 microgram/ml particulate protein, the concentration of protein that yielded maximum binding. Nevertheless, the majority of experiments were conducted at lesser protein concentrations and at physiological pH (7.45), under which conditions total binding was only 25% of that measured at pH 5.5. Scatchard plots indicated the presence of a single binding site with a dissociation constant of 5.8 X 10(-8) M and a binding capacity of 0.22 nmol/mg protein on the basis of data obtained at 22 C and pH 7.45. Both crude and highly purified preparations of hCG inhibited the binding of [125I]bTSH to testis particulate fraction; crude hCG had 46 times the activity, and purified hCG had only one-tenth the activity of bTSH itself in this respect. This was true despite the fact that with respect to the displacement of [125I]hCG, crude and purified hCG were almost equally active. Bovine LH had one-third the activity of bTSH in displacing [125I]bTSH. Human FSH inhibited [125I]bTSH binding only slightly at the highest concentration tested, while glucagon, insulin, PRL, and GH were inactive. Purified bTSH inhibited the binding of [125I]hCG to testis particulate fraction but contained only about 2% of the activity of purified hCG. Lineweaver-Burk analysis suggested that inhibition of [125I]hCG binding by bTSH was competitive in nature. Purified bTSH stimulated cAMP production in Leydig cells, but with only about 0.1% of the activity of purified hCG. It is concluded that bTSH binds reversibly, saturably, and with relatively high affinity to receptors in rat testis that are either the same as receptors for hCG and LH or that interact therewith. bTSH, like hCG, is capable of stimulating the production of cAMP in rat Leydig cells, but is much less potent than hCG in this regard. Preparations of crude hCG contain a factor lacking hCG activity in bioassay, immunoassay, and receptor assay that is especially potent in displacing [125I]bTSH from receptors in testis, as has earlier been described for bTSH receptors in bovine thyroid membranes."}
{"id": "PMID:217637", "title": "Developmental changes in testicular gonadotropin receptors: plasma gonadotropins and plasma testosterone in the rat.", "content": "The relationships between plasma gonadotropins, testicular gonadotropin receptors, and plasma testosterone were examined during neonatal life and throughout sexual maturation in the rat. The binding affinity of testicular LH receptors (2.4 X 10(10) M-1) was significantly higher than that of FSH receptors (2.1 X 10(9) M-1) at all stages of development. The concentration of FSH receptors in the testis reached a peak between 10-15 days of age, then fell to a constant level from 25-90 days. However, the testis content of FSH receptors increased continually with age and reached a plateau at day 60. Plasma FSH declined after birth to a nadir at 15 days, then rose rapidly to a peak at day 38, and fell to a plateau from day 50 through adult life. In contrast to the rapidly changing profile of plasma FSH during early maturation, alterations in plasma LH were less marked throughout development. Although a progressive rise in plasma LH concentration was observed between days 36-51, the simultaneous changes in testicular LH receptors and plasma testosterone were much more prominent. Testicular LH receptors showed a continuous increase in concentration and total number with advancing age and testis growth. The major rise in LH receptor concentration occurred between 15-38 days age, at the same time as the rise in plasma FSH concentration and the phase of rapid testicular growth. Plasma testosterone fell during the 8th-24th days after birth, then rose rapidly between days 35-55. The pubertal rise in plasma testosterone occurred about 15 days after testicular LH receptors began to increase and was coincident with the continuing rise in LH receptor content from day 35 until day 55 and with the progressive increase in plasma LH during this period. These observations have demonstrated that the early development of testicular FSH receptors in followed by a prominent rise in plasma FSH, with concomitant increases in testicular growth and LH receptor concentration. The resulting increase in gonadal sensitivity to LH could be responsible for the marked increase in secretion of testosterone which occurs during puberty in the presence of a relatively small change in the circulating LH concentration. The sequence of changes observed in gonadotropins and their testicular receptors is consistent with the view that FSH-induced testicular sensitivity to LH is an important factor in sexual maturation in the male rat.", "contents": "Developmental changes in testicular gonadotropin receptors: plasma gonadotropins and plasma testosterone in the rat. The relationships between plasma gonadotropins, testicular gonadotropin receptors, and plasma testosterone were examined during neonatal life and throughout sexual maturation in the rat. The binding affinity of testicular LH receptors (2.4 X 10(10) M-1) was significantly higher than that of FSH receptors (2.1 X 10(9) M-1) at all stages of development. The concentration of FSH receptors in the testis reached a peak between 10-15 days of age, then fell to a constant level from 25-90 days. However, the testis content of FSH receptors increased continually with age and reached a plateau at day 60. Plasma FSH declined after birth to a nadir at 15 days, then rose rapidly to a peak at day 38, and fell to a plateau from day 50 through adult life. In contrast to the rapidly changing profile of plasma FSH during early maturation, alterations in plasma LH were less marked throughout development. Although a progressive rise in plasma LH concentration was observed between days 36-51, the simultaneous changes in testicular LH receptors and plasma testosterone were much more prominent. Testicular LH receptors showed a continuous increase in concentration and total number with advancing age and testis growth. The major rise in LH receptor concentration occurred between 15-38 days age, at the same time as the rise in plasma FSH concentration and the phase of rapid testicular growth. Plasma testosterone fell during the 8th-24th days after birth, then rose rapidly between days 35-55. The pubertal rise in plasma testosterone occurred about 15 days after testicular LH receptors began to increase and was coincident with the continuing rise in LH receptor content from day 35 until day 55 and with the progressive increase in plasma LH during this period. These observations have demonstrated that the early development of testicular FSH receptors in followed by a prominent rise in plasma FSH, with concomitant increases in testicular growth and LH receptor concentration. The resulting increase in gonadal sensitivity to LH could be responsible for the marked increase in secretion of testosterone which occurs during puberty in the presence of a relatively small change in the circulating LH concentration. The sequence of changes observed in gonadotropins and their testicular receptors is consistent with the view that FSH-induced testicular sensitivity to LH is an important factor in sexual maturation in the male rat."}
{"id": "PMID:217640", "title": "Binding of thyroid stimulators to guinea pig testis and thyroid.", "content": "We have demonstrated TSH binding sites in membranes prepared from guinea pig testis. The binding of TSH to testicular homogenate was localized to the interstitial tissue and showed similar characteristics to the binding of TSH to thyroid membranes with high affinity (Ka = 2.5 X 10(10) M-1) but limited capacity (approximately 0.9-1.7 pg/mg equivalent testis homogenate). In addition, thyroid-stimulating antibodies inhibited the binding of TSH to both testicular and thyroid homogenate but failed to inhibit the binding of hCG to the testis preparation. These data suggested that the TSH-binding site was distinct from the hCG/LH binding site. Testicular and thyroid TSH-binding sites also appeared to demonstrate a similar degree of cross-reactivity with a crude preparation of hCG. In conclusion, our findings suggest that thyroid-stimulators may influence gonadal function. Furthermore, the ability of hCG to inhibit the binding of TSH to thyroid membranes provides a possible mechanism for the known thyroid-stimulating properties of hCG.", "contents": "Binding of thyroid stimulators to guinea pig testis and thyroid. We have demonstrated TSH binding sites in membranes prepared from guinea pig testis. The binding of TSH to testicular homogenate was localized to the interstitial tissue and showed similar characteristics to the binding of TSH to thyroid membranes with high affinity (Ka = 2.5 X 10(10) M-1) but limited capacity (approximately 0.9-1.7 pg/mg equivalent testis homogenate). In addition, thyroid-stimulating antibodies inhibited the binding of TSH to both testicular and thyroid homogenate but failed to inhibit the binding of hCG to the testis preparation. These data suggested that the TSH-binding site was distinct from the hCG/LH binding site. Testicular and thyroid TSH-binding sites also appeared to demonstrate a similar degree of cross-reactivity with a crude preparation of hCG. In conclusion, our findings suggest that thyroid-stimulators may influence gonadal function. Furthermore, the ability of hCG to inhibit the binding of TSH to thyroid membranes provides a possible mechanism for the known thyroid-stimulating properties of hCG."}
{"id": "PMID:217642", "title": "Role of the carbohydrate residues of human chorionic gonadotropin in binding and stimulation of adenosine 3',5'-monophosphate accumulation by porcine granulosa cells.", "content": "Removal of the sugar residues internal to sialic acid from the hCG molecule markedly diminished the ability of hCG to stimulate cAMP accumulation by porcine granulosa cells during a 30-min incubation period. At the same time, removal of sugars internal to sialic acid enabled the resulting hCG derivatives to become competitive inhibitors of hCG stimulation of cAMP accumulation. This contrasts with the finding that removal of sugars internal to sialic acid residues has a lesser effect on the ability of hCG to inhibit the binding of human [125I]iodo-CG to granulosa cells, provided the hCG derivatives were added before the tracer. It would, therefore, seem that hCG with sugars internal to sialic acid removed is able to bind to the receptor, but that, once bound, it is unable to activate adenylate cyclase. Under these conditions, it can also act as a competitive inhibitor of hCG stimulation of cAMP accumulation.", "contents": "Role of the carbohydrate residues of human chorionic gonadotropin in binding and stimulation of adenosine 3',5'-monophosphate accumulation by porcine granulosa cells. Removal of the sugar residues internal to sialic acid from the hCG molecule markedly diminished the ability of hCG to stimulate cAMP accumulation by porcine granulosa cells during a 30-min incubation period. At the same time, removal of sugars internal to sialic acid enabled the resulting hCG derivatives to become competitive inhibitors of hCG stimulation of cAMP accumulation. This contrasts with the finding that removal of sugars internal to sialic acid residues has a lesser effect on the ability of hCG to inhibit the binding of human [125I]iodo-CG to granulosa cells, provided the hCG derivatives were added before the tracer. It would, therefore, seem that hCG with sugars internal to sialic acid removed is able to bind to the receptor, but that, once bound, it is unable to activate adenylate cyclase. Under these conditions, it can also act as a competitive inhibitor of hCG stimulation of cAMP accumulation."}
{"id": "PMID:217646", "title": "Thyroid hormone receptors from liver nuclei: characteristics of receptor from normal, thyroidectomized, and triiodothyronine-treated rats; measurement of occupied and unoccupied receptors, and chromatin binding of receptors.", "content": "The capacity and characteristics of liver nuclear receptors for T3 have been compared in normal rats, thyroidectomized rats, and thyroidectomized rats treated with different doses of T3. Receptor capacity was unchanged, with the exception of a decrease of total nuclear receptors in rats treated with 15 microgram T3/day, which is believed due to lack of complete dissociation of the endogenously bound hormone during incubation in vitro. During incubation of the isolated nuclei in 0.32 M sucrose plus 1 mM MgCl2 plus 20 mM Tris-Cl buffer, pH 7.85, about 50% of the nuclear receptors were released to the medium and no effect of T3 treatment on the amount released was found. The affinity of the receptors free in solution was 50% higher than that of receptors retained in the nuclei. Receptors from normal and thyroidectomized rats were studied by ultracentrifugation through sucrose gradients. No difference in sedimentation coefficient was found between the groups of rats, whether the receptors were filled with the labeled hormone before or after centrifugation and separation of the gradient fractions. Occupied and unoccupied receptor capacity was estimated by incubation of receptor preparations at 20 and 0 C for 2 h. Observed capacity at 20 C represents unoccupied plus approximately 80% of occupied sites, while observed capacity at 0 C represents unoccupied plus 10% of occupied site. Binding of receptors to the chromatin was studied by incubating nuclear extract from normal rats with chromatin and measuring the amount of receptor that was not bound and remained free in the supernatant. Receptor not bound to chromatin was incubated at 0 and 20 C, with a saturating concentration of [125I]T3, to measure occupied and unoccupied sites. Both occupied and unoccupied receptor decrease in the supernatant after incubation with the chromatin when the concentration of chromatin in the incubation medium is increased. No saturation of the chromatin-binding sites was achieved by increasing the concentration of receptor several-fold, and no difference in the binding of occupied and unoccupied receptors to chromatin was observed. These data rule out the possibility that the concentration of receptors in the nucleus is under control of the hormone. Major molecular changes of the receptor that could be induced by T3, such as dissociation into subunits, are also ruled out. Binding studies to the chromatin are not necessarily conclusive, as nonspecific binding may be masking the physiological binding of the receptors to a limited number of acceptor sites.", "contents": "Thyroid hormone receptors from liver nuclei: characteristics of receptor from normal, thyroidectomized, and triiodothyronine-treated rats; measurement of occupied and unoccupied receptors, and chromatin binding of receptors. The capacity and characteristics of liver nuclear receptors for T3 have been compared in normal rats, thyroidectomized rats, and thyroidectomized rats treated with different doses of T3. Receptor capacity was unchanged, with the exception of a decrease of total nuclear receptors in rats treated with 15 microgram T3/day, which is believed due to lack of complete dissociation of the endogenously bound hormone during incubation in vitro. During incubation of the isolated nuclei in 0.32 M sucrose plus 1 mM MgCl2 plus 20 mM Tris-Cl buffer, pH 7.85, about 50% of the nuclear receptors were released to the medium and no effect of T3 treatment on the amount released was found. The affinity of the receptors free in solution was 50% higher than that of receptors retained in the nuclei. Receptors from normal and thyroidectomized rats were studied by ultracentrifugation through sucrose gradients. No difference in sedimentation coefficient was found between the groups of rats, whether the receptors were filled with the labeled hormone before or after centrifugation and separation of the gradient fractions. Occupied and unoccupied receptor capacity was estimated by incubation of receptor preparations at 20 and 0 C for 2 h. Observed capacity at 20 C represents unoccupied plus approximately 80% of occupied sites, while observed capacity at 0 C represents unoccupied plus 10% of occupied site. Binding of receptors to the chromatin was studied by incubating nuclear extract from normal rats with chromatin and measuring the amount of receptor that was not bound and remained free in the supernatant. Receptor not bound to chromatin was incubated at 0 and 20 C, with a saturating concentration of [125I]T3, to measure occupied and unoccupied sites. Both occupied and unoccupied receptor decrease in the supernatant after incubation with the chromatin when the concentration of chromatin in the incubation medium is increased. No saturation of the chromatin-binding sites was achieved by increasing the concentration of receptor several-fold, and no difference in the binding of occupied and unoccupied receptors to chromatin was observed. These data rule out the possibility that the concentration of receptors in the nucleus is under control of the hormone. Major molecular changes of the receptor that could be induced by T3, such as dissociation into subunits, are also ruled out. Binding studies to the chromatin are not necessarily conclusive, as nonspecific binding may be masking the physiological binding of the receptors to a limited number of acceptor sites."}
{"id": "PMID:217647", "title": "Rabbit ovarian protein kinases. I. Effect of an ovulatory dose of human chorionic gonadotropin or luteinizing hormone on the subcellular distribution of follicular and luteal protein kinases.", "content": "Studies on the subcellular distribution of protein kinase activity in popped estrous follicles from rabbit ovaries revealed that 15% of the total cellular protein kinase activity was compartmentalized in the nuclear, mitochondrial, and microsomal fractions. About 50% of the particulate protein kinase activity was unaffected by the heat-stable protein kinase inhibitor and was thus cAMP-independent. The majority of cellular protein kinase activity was identified in the 105,000 X g supernatant fraction as cAMP-dependent. hCG- or coital-induced ovulation and subsequent corpus luteum (CL) formation, and hCG-induced luteal regression promoted changes and a redistribution of protein kinase activity among the subcellular fractions. In follicles, hCG promoted a transient decline of nuclear protein kinase activity as well as transient increases of the relative amount of protein kinases localized in the microsomal fractions before ovulation. In CL induced by a fertile mating, the specific activity as well as the total amount of protein kinases in the nuclear fraction were reduced 2-fold. Mitochondrial protein kinase activity from CL of pseudopregnancy and pregnancy was reduced 2-fold. The relative amount of protein kinase activity in microsomes of CL was increased 2-fold, but the specific activity was not affected. hCG-induced luteal regression resulted in a transient decline of the nuclear protein kinase activity in CL of 4-day pseudopregnant rabbits. In interstitial tissue, the specific activity of the nuclear protein kinase was increased over luteal levels, the mitochondrial-specific protein kinase remained at the reduced luteal levels, and the microsomal and cytosol protein kinase specific activities increased 2-fold. Studies with the heat-stable protein kinase inhibitor revealed that the hCG- or coital-induced redistribution of intracellular protein kinase affected both the cAMP-dependent and cAMP-independent activity to a similar degree and no changes of the relative distribution of cAMP-dependent vs. cAMP-independent activity were observed. These results indicate that the intracellular distribution and enzymatic activity of cAMP-dependent protein kinases in ovarian structures are subject to regulation by LH (hCG) and depend upon the various reproductive stages of the rabbit.", "contents": "Rabbit ovarian protein kinases. I. Effect of an ovulatory dose of human chorionic gonadotropin or luteinizing hormone on the subcellular distribution of follicular and luteal protein kinases. Studies on the subcellular distribution of protein kinase activity in popped estrous follicles from rabbit ovaries revealed that 15% of the total cellular protein kinase activity was compartmentalized in the nuclear, mitochondrial, and microsomal fractions. About 50% of the particulate protein kinase activity was unaffected by the heat-stable protein kinase inhibitor and was thus cAMP-independent. The majority of cellular protein kinase activity was identified in the 105,000 X g supernatant fraction as cAMP-dependent. hCG- or coital-induced ovulation and subsequent corpus luteum (CL) formation, and hCG-induced luteal regression promoted changes and a redistribution of protein kinase activity among the subcellular fractions. In follicles, hCG promoted a transient decline of nuclear protein kinase activity as well as transient increases of the relative amount of protein kinases localized in the microsomal fractions before ovulation. In CL induced by a fertile mating, the specific activity as well as the total amount of protein kinases in the nuclear fraction were reduced 2-fold. Mitochondrial protein kinase activity from CL of pseudopregnancy and pregnancy was reduced 2-fold. The relative amount of protein kinase activity in microsomes of CL was increased 2-fold, but the specific activity was not affected. hCG-induced luteal regression resulted in a transient decline of the nuclear protein kinase activity in CL of 4-day pseudopregnant rabbits. In interstitial tissue, the specific activity of the nuclear protein kinase was increased over luteal levels, the mitochondrial-specific protein kinase remained at the reduced luteal levels, and the microsomal and cytosol protein kinase specific activities increased 2-fold. Studies with the heat-stable protein kinase inhibitor revealed that the hCG- or coital-induced redistribution of intracellular protein kinase affected both the cAMP-dependent and cAMP-independent activity to a similar degree and no changes of the relative distribution of cAMP-dependent vs. cAMP-independent activity were observed. These results indicate that the intracellular distribution and enzymatic activity of cAMP-dependent protein kinases in ovarian structures are subject to regulation by LH (hCG) and depend upon the various reproductive stages of the rabbit."}
{"id": "PMID:217648", "title": "Rabbit ovarian protein kinases. III. Gonadotrophin-induced activation of soluble adenosine 3',5'-monophosphate-dependent protein kinases.", "content": "Cytosol of mature estrous rabbit follicles contains a single species of protein kinase, protein kinase 3, which can be classified as a type II cAMP-dependent protein kinase. Cytosol of functional rabbit corpora lutea (CL) contains, in addition to protein kinase 3, a second species of kinase activity, protein kinase 2, which can be classified as a type I cAMP-dependent protein kinase. These conclusions are based upon the relative dissociation and reassociation characteristics of the two holoenzymes in the presence and absence of 0.5 M NaCl after in vitro dissociation by cAMP, upon the effect of MgATP on salt- and basic protein-induced dissociation, and upon their relative elution from DEAE-cellulose. Protein kinase 3 in mature estrous rabbit follicles was rapidly activated after an iv injection of hCG. The activation was demonstrated by an increase of the protein kinase activity ratio as well as by the appearance of the free catalytic subunit of protein kinase upon Sephadex gel filtration. Maximal activation occurred within 10 min of in vivo hormone administration and required ovulatory doses of hormones with LH-like activity. Neither PRL, ACTH, epinephrine, nor a highly purified preparation of FSH promoted activation of the follicular protein kinase 3. Demonstration of protein kinase activation in follicles was achieved in the presence of 0.5 M NaCl in the homogenization media. After an iv injection of hCG, a partial activation of luteal protein kinases 2 and 3 was demonstrated, as reflected by the increase of the protein kinase activity ratio. These results implicate an important role for cAMP-dependent protein kinase 3 in LH action in rabbit ovarian follicles and for cAMP-dependent protein kinases 2 and 3 in LH action in rabbit CL.", "contents": "Rabbit ovarian protein kinases. III. Gonadotrophin-induced activation of soluble adenosine 3',5'-monophosphate-dependent protein kinases. Cytosol of mature estrous rabbit follicles contains a single species of protein kinase, protein kinase 3, which can be classified as a type II cAMP-dependent protein kinase. Cytosol of functional rabbit corpora lutea (CL) contains, in addition to protein kinase 3, a second species of kinase activity, protein kinase 2, which can be classified as a type I cAMP-dependent protein kinase. These conclusions are based upon the relative dissociation and reassociation characteristics of the two holoenzymes in the presence and absence of 0.5 M NaCl after in vitro dissociation by cAMP, upon the effect of MgATP on salt- and basic protein-induced dissociation, and upon their relative elution from DEAE-cellulose. Protein kinase 3 in mature estrous rabbit follicles was rapidly activated after an iv injection of hCG. The activation was demonstrated by an increase of the protein kinase activity ratio as well as by the appearance of the free catalytic subunit of protein kinase upon Sephadex gel filtration. Maximal activation occurred within 10 min of in vivo hormone administration and required ovulatory doses of hormones with LH-like activity. Neither PRL, ACTH, epinephrine, nor a highly purified preparation of FSH promoted activation of the follicular protein kinase 3. Demonstration of protein kinase activation in follicles was achieved in the presence of 0.5 M NaCl in the homogenization media. After an iv injection of hCG, a partial activation of luteal protein kinases 2 and 3 was demonstrated, as reflected by the increase of the protein kinase activity ratio. These results implicate an important role for cAMP-dependent protein kinase 3 in LH action in rabbit ovarian follicles and for cAMP-dependent protein kinases 2 and 3 in LH action in rabbit CL."}
{"id": "PMID:217654", "title": "Converting enzyme inhibition augments and competitive inhibition of angiotensin II partially restores reflex adrenal catecholamine release in anephric dogs.", "content": "Adrenal epinephrine (E) release after hemorrhage in anesthetized dogs is blunted by acute nephrectomy and restored by angiotensin II infusion. In the present study, we report the effect of converting enzyme inhibition by SQ 20881, a decapeptide, and of competition inhibition of angiotensin II by saralasin (1-Sar-8-Ala-Ang-II) on reflexly stimulated adrenal release of E and norepinephrine (NE) in three groups of acutely anephric dogs. Aortic catheters and adrenal vein to femoral vein Silastic shunts were placed in dogs anesthetized with pentobarbital and mechanically ventilated. Adrenal secretion rates were calculated from adrenal vein to aorta catecholamine concentration differences divided by measured adrenal venous flow. Catecholamine concentrations were determined with trihydroxyindole technique. Blood samples were obtained before and 15, 30, and 60 min after rapid hemorrhage to a stable mean arterial pressure of 50 mm Hg. Saralasin infusion (10 microgram/kg/min) supported adrenal E release in anephric hemorrhaged dogs toward secretion rates comparable to those seen in intact dogs. Anephric SQ 20881 (approximately 0.5 microgram/kg) recipients had delayed (60 min) augmented adrenal E and NE release after hemorrhage. In resting animals not reflexly stimulated by hypovolemia, neither drug provoked adrenal E or NE release. These results suggest an agonist effect of saralasin on reflex adrenal E release and increased responsiveness of the stimulated adrenal medulla under the influence of converting enzyme inhibition.", "contents": "Converting enzyme inhibition augments and competitive inhibition of angiotensin II partially restores reflex adrenal catecholamine release in anephric dogs. Adrenal epinephrine (E) release after hemorrhage in anesthetized dogs is blunted by acute nephrectomy and restored by angiotensin II infusion. In the present study, we report the effect of converting enzyme inhibition by SQ 20881, a decapeptide, and of competition inhibition of angiotensin II by saralasin (1-Sar-8-Ala-Ang-II) on reflexly stimulated adrenal release of E and norepinephrine (NE) in three groups of acutely anephric dogs. Aortic catheters and adrenal vein to femoral vein Silastic shunts were placed in dogs anesthetized with pentobarbital and mechanically ventilated. Adrenal secretion rates were calculated from adrenal vein to aorta catecholamine concentration differences divided by measured adrenal venous flow. Catecholamine concentrations were determined with trihydroxyindole technique. Blood samples were obtained before and 15, 30, and 60 min after rapid hemorrhage to a stable mean arterial pressure of 50 mm Hg. Saralasin infusion (10 microgram/kg/min) supported adrenal E release in anephric hemorrhaged dogs toward secretion rates comparable to those seen in intact dogs. Anephric SQ 20881 (approximately 0.5 microgram/kg) recipients had delayed (60 min) augmented adrenal E and NE release after hemorrhage. In resting animals not reflexly stimulated by hypovolemia, neither drug provoked adrenal E or NE release. These results suggest an agonist effect of saralasin on reflex adrenal E release and increased responsiveness of the stimulated adrenal medulla under the influence of converting enzyme inhibition."}
{"id": "PMID:217655", "title": "Studies on the dissociation of prolactin from mammary tumor membranes.", "content": "The dissociation of [125I]iodo-PRL from crude membrane preparations of two transplantable rat mammary carcinomas was studied. At least 1/2 of the specifically bound PRL remains undissociated when membrane pellets are resuspended in buffer. The apparent irreversibly bound fraction can be removed at least partially upon incubation with 6 M urea, but not with 1 M urea. By all the criteria used, the dissociated PRL was undamaged. The physiological importance of this phenomenon may relate to the presence of more than one type of binding site which current techniques do not allow us to distinguish.", "contents": "Studies on the dissociation of prolactin from mammary tumor membranes. The dissociation of [125I]iodo-PRL from crude membrane preparations of two transplantable rat mammary carcinomas was studied. At least 1/2 of the specifically bound PRL remains undissociated when membrane pellets are resuspended in buffer. The apparent irreversibly bound fraction can be removed at least partially upon incubation with 6 M urea, but not with 1 M urea. By all the criteria used, the dissociated PRL was undamaged. The physiological importance of this phenomenon may relate to the presence of more than one type of binding site which current techniques do not allow us to distinguish."}
{"id": "PMID:217656", "title": "Interactions of gonadotropins with corpus luteum membranes. I. Properties and distributions of some marker enzyme activities after subcellular fractionation of the superovulated rat ovary.", "content": "The properties of a number of enzyme activities of the superovulated rat ovary have been studied to establish optimal assay conditions and specific assay procedures for each activity. The activities were chosen on the basis of their extensive use in other tissues of the rat as marker enzymes for the major cell organelles. Homogenates of superovulated rat ovaries were subjected to fractionation by differential rate centrifugation, and sedimentation profiles were constructed for each marker enzyme activity. The various subcellular fractions were also monitored by electron microscopy. The enrichment of fractions with particular organelles by electron microscopy, and enrichment of the appropriate organelle marker enzyme activities correlated well. Sedimentation profiles of a number of plasma membrane marker enzymes demonstrated a marked discrepancy between hCG-binding activity, and 5'-nucleotidase-, alkaline phosphatase-, and Mg2+-dependent ATP-ase on the one hand, and basal, hCG-stimulated, and fluoride-stimulated adenylate cyclase activities on the other hand. Fractions enriched in hCG-binding and adenylate cyclase activities were subjected to further fractionation on discontinuous sucrose density gradients. The distributions of the various plasma membrane markers again indicated a partial dissociations between hCG-binding and adenylate cyclase activities of luteinized rat ovaries, suggesting the existence of two distinct major plasma membrane populations, with different buoyant densities, marker enzyme profiles and adenylate cyclase and hormone-binding levels.", "contents": "Interactions of gonadotropins with corpus luteum membranes. I. Properties and distributions of some marker enzyme activities after subcellular fractionation of the superovulated rat ovary. The properties of a number of enzyme activities of the superovulated rat ovary have been studied to establish optimal assay conditions and specific assay procedures for each activity. The activities were chosen on the basis of their extensive use in other tissues of the rat as marker enzymes for the major cell organelles. Homogenates of superovulated rat ovaries were subjected to fractionation by differential rate centrifugation, and sedimentation profiles were constructed for each marker enzyme activity. The various subcellular fractions were also monitored by electron microscopy. The enrichment of fractions with particular organelles by electron microscopy, and enrichment of the appropriate organelle marker enzyme activities correlated well. Sedimentation profiles of a number of plasma membrane marker enzymes demonstrated a marked discrepancy between hCG-binding activity, and 5'-nucleotidase-, alkaline phosphatase-, and Mg2+-dependent ATP-ase on the one hand, and basal, hCG-stimulated, and fluoride-stimulated adenylate cyclase activities on the other hand. Fractions enriched in hCG-binding and adenylate cyclase activities were subjected to further fractionation on discontinuous sucrose density gradients. The distributions of the various plasma membrane markers again indicated a partial dissociations between hCG-binding and adenylate cyclase activities of luteinized rat ovaries, suggesting the existence of two distinct major plasma membrane populations, with different buoyant densities, marker enzyme profiles and adenylate cyclase and hormone-binding levels."}
{"id": "PMID:217657", "title": "Interactions of gonadotropins with corpus luteum membranes. II. The identification of two distinct surface membrane fractions from superovulated rat ovaries.", "content": "Fractions enriched in hCG-binding activity were prepared by differential rate centrifugation of superovulated rat ovarian homogenates and were applied to continuous sucrose density gradients (20-55%). After centrifugation at 63,000 x gav for 3.5 h, fractions of each gradient were collected and assayed for a range of marker enzyme activities characteristic of surface membranes and subcellular organelles. Mitochondria, lysosomes, and rough and smooth endoplasmic reticulum membranes accumulated in the gradient between 38-41% sucrose (1.165-1.180 g/cm3). Nuclei passed through the gradient. However, the various surface membrane markers concentrated in two distinct regions of the gradient. Alkaline phosphatase, phosphodiesterase, (Na+ + K+)ATPase I, and hCG-binding activity concentrated at 29-32% sucrose (1.120-1.135 g/cm3), whereas 5'-nucleotidase, Mg2+-dependent ATPase, and adenylate cyclase activities (and minor peaks of hCG-binding and phosphodiesterase activities) were enriched at 36-38% sucrose (1.16-1.17 g/cm3). A second ATPase, [(Na+ + K+)ATPase II], was also observed in this region of the gradient, which could be distinguished from (Na+ + K+)ATPase I of the light membrane fraction by its sensitivity to the Ca2+-chelating agent, ethylene glycol bis-(aminoethyl)tetraacetic acid (EGTA). The kinetics of binding of radioiodinated hCG to the gonadotropin receptors of the light and heavy membrane fractions were very similar. It is suggested that fractionation of superovulated rat ovaries yields two distinct populations of surface membrane material which have distinct densities and marker enzyme profiles. Furthermore, in contrast to the heavy membrane fraction, light membranes seem to possess considerable amounts of hCG receptor activity but very little adenylate cyclase.", "contents": "Interactions of gonadotropins with corpus luteum membranes. II. The identification of two distinct surface membrane fractions from superovulated rat ovaries. Fractions enriched in hCG-binding activity were prepared by differential rate centrifugation of superovulated rat ovarian homogenates and were applied to continuous sucrose density gradients (20-55%). After centrifugation at 63,000 x gav for 3.5 h, fractions of each gradient were collected and assayed for a range of marker enzyme activities characteristic of surface membranes and subcellular organelles. Mitochondria, lysosomes, and rough and smooth endoplasmic reticulum membranes accumulated in the gradient between 38-41% sucrose (1.165-1.180 g/cm3). Nuclei passed through the gradient. However, the various surface membrane markers concentrated in two distinct regions of the gradient. Alkaline phosphatase, phosphodiesterase, (Na+ + K+)ATPase I, and hCG-binding activity concentrated at 29-32% sucrose (1.120-1.135 g/cm3), whereas 5'-nucleotidase, Mg2+-dependent ATPase, and adenylate cyclase activities (and minor peaks of hCG-binding and phosphodiesterase activities) were enriched at 36-38% sucrose (1.16-1.17 g/cm3). A second ATPase, [(Na+ + K+)ATPase II], was also observed in this region of the gradient, which could be distinguished from (Na+ + K+)ATPase I of the light membrane fraction by its sensitivity to the Ca2+-chelating agent, ethylene glycol bis-(aminoethyl)tetraacetic acid (EGTA). The kinetics of binding of radioiodinated hCG to the gonadotropin receptors of the light and heavy membrane fractions were very similar. It is suggested that fractionation of superovulated rat ovaries yields two distinct populations of surface membrane material which have distinct densities and marker enzyme profiles. Furthermore, in contrast to the heavy membrane fraction, light membranes seem to possess considerable amounts of hCG receptor activity but very little adenylate cyclase."}
{"id": "PMID:217659", "title": "alpha-Adrenergic inhibition of adenosine 3',5'-monophosphate accumulation and parathyroid hormone release from dispersed bovine parathyroid cells.", "content": "The possibility of alpha-adrenergic modulation of cAMP accumulation and parathyroid hormone (PTH) release was investigated in dispersed bovine parathyroid cells. cAMP accumulation due to the mixed alpha- and beta-adrenergic agonists, (-)epinephrine and (-)norepinephrine, was significantly enhanced by the alpha-adrenergic inhibitor phentolamine; that due to the \"pure\" beta-adrenergic agonist, (-)isoproterenol, was not altered significantly. Direct inhibition of agonist-stimulated cAMP accumulation was effected by adding increasing concentrations of (-)epinephrine to concentrations of (-)isoproterenol maximally stimulating cAMP accumulation. A 50-75% inhibition of cAMP was observed which was specifically blocked by phentolamine. This inhibition was not specific for beta-adrenergic stimulation, as (-)epinephrine also inhibited dopamine-stimulated cAMP accumulation. The inhibition of (-)isoproterenol-stimulated cAMP accumulation by (-)epinephrine was unaffected by ambient calcium concentration. Stimulation of PTH release by (-)epinephrine and (-)norepinephrine was potentiated by phentolamine and inhibited by the beta-adrenergic blocker, (-)propranolol, demonstrating alpha-adrenergic modulation of hormone release and confirming the close relationship between cAMP accumulation and PTH release previously shown in this system. These results demonstrate the presence of an alpha-adrenergic receptor in dispersed bovine parathyroid cells which inhibits agonist-stimulated cAMP accumulation and PTH release by a mechanism independent of extracellular calcium.", "contents": "alpha-Adrenergic inhibition of adenosine 3',5'-monophosphate accumulation and parathyroid hormone release from dispersed bovine parathyroid cells. The possibility of alpha-adrenergic modulation of cAMP accumulation and parathyroid hormone (PTH) release was investigated in dispersed bovine parathyroid cells. cAMP accumulation due to the mixed alpha- and beta-adrenergic agonists, (-)epinephrine and (-)norepinephrine, was significantly enhanced by the alpha-adrenergic inhibitor phentolamine; that due to the \"pure\" beta-adrenergic agonist, (-)isoproterenol, was not altered significantly. Direct inhibition of agonist-stimulated cAMP accumulation was effected by adding increasing concentrations of (-)epinephrine to concentrations of (-)isoproterenol maximally stimulating cAMP accumulation. A 50-75% inhibition of cAMP was observed which was specifically blocked by phentolamine. This inhibition was not specific for beta-adrenergic stimulation, as (-)epinephrine also inhibited dopamine-stimulated cAMP accumulation. The inhibition of (-)isoproterenol-stimulated cAMP accumulation by (-)epinephrine was unaffected by ambient calcium concentration. Stimulation of PTH release by (-)epinephrine and (-)norepinephrine was potentiated by phentolamine and inhibited by the beta-adrenergic blocker, (-)propranolol, demonstrating alpha-adrenergic modulation of hormone release and confirming the close relationship between cAMP accumulation and PTH release previously shown in this system. These results demonstrate the presence of an alpha-adrenergic receptor in dispersed bovine parathyroid cells which inhibits agonist-stimulated cAMP accumulation and PTH release by a mechanism independent of extracellular calcium."}
{"id": "PMID:217660", "title": "Studies on the site of action of vasopressin in inducing adrenocorticotropin secretion.", "content": "Hypophysectomized rats bearing three transplanted pituitaries under the kidney capsule responded to synthetic lysine vasopressin or pitressin with a significant elevation of plasma corticosterone, whereas hypophysectomized rats with no grafts did not. This response was completely abolished by pretreatment of animals with dexamethasone but was unaltered by central hypothalamic destruction. Corticotropin-releasing factor content of the hypothalamic median eminence, hypophyseal stal-, or pars nervosa of the posterior pituitary of intact rats was unchanged 5 or 10 min after ip injection of vasopressin compared to the basal level. We conclude that vasopressin and dexamethasone act directly on the adenohypophysis in vivo to exert their stimulatory or inhibitory effect on ACTH secretion.", "contents": "Studies on the site of action of vasopressin in inducing adrenocorticotropin secretion. Hypophysectomized rats bearing three transplanted pituitaries under the kidney capsule responded to synthetic lysine vasopressin or pitressin with a significant elevation of plasma corticosterone, whereas hypophysectomized rats with no grafts did not. This response was completely abolished by pretreatment of animals with dexamethasone but was unaltered by central hypothalamic destruction. Corticotropin-releasing factor content of the hypothalamic median eminence, hypophyseal stal-, or pars nervosa of the posterior pituitary of intact rats was unchanged 5 or 10 min after ip injection of vasopressin compared to the basal level. We conclude that vasopressin and dexamethasone act directly on the adenohypophysis in vivo to exert their stimulatory or inhibitory effect on ACTH secretion."}
{"id": "PMID:217662", "title": "Organization of the medial hypothalamus for control of adrenocorticotropin in the cat.", "content": "To examine the role and interrelations of areas of the medial hypothalamus in the control of release of ACTH, we stimulated electrically (20-sec train, 200-microamperemeter amplitude at 100 Hz) 695 sites in the hypothalamus of 91 cats anesthetized with chloralose-urethane. Changes in ACTH were measured by RIA. Responses of arterial pressure could not account for changes of release of ACTH. Several ACTH-active areas were defined. The anatomical relations of these areas with known nuclei and pathways then were considered. Two ACTH facilitatory areas and one ACTH inhibitory area were identified in the lateral aspect of the medial hypothalamus. The dorsal facilitatory area appears to be an extension of the lateral division of the dorsolongitudinal fasciculus and to extend medially to join the Fields of Forel, the ventral tegmental area of Tsai, and the parvocellular, paraventricular, and periventricular nuclei. The ACTH inhibitory area appears to be an extension of portions of the central tegmental tract and to extend medially to the posterior hypothalamic area and the dorsal hypothalamic area and ventrally toward the basal hypothalamus. The ventral ACTH facilitatory area appears to be coincident with the medial forebrain bundle and to extend anteroventrally and medially through the supraoptic decussation to the suprachiasmatic, ventromedial, dorsomedial, periventricular, infundibular, and premammillary nuclei. Stimulation of the median eminence led to increased release of ACTH. The results suggest that ascending pathways from the lower brainstem mediating control of ACTH project to discrete areas of the hypothalamus and then converge on the medial basal hypothalamus.", "contents": "Organization of the medial hypothalamus for control of adrenocorticotropin in the cat. To examine the role and interrelations of areas of the medial hypothalamus in the control of release of ACTH, we stimulated electrically (20-sec train, 200-microamperemeter amplitude at 100 Hz) 695 sites in the hypothalamus of 91 cats anesthetized with chloralose-urethane. Changes in ACTH were measured by RIA. Responses of arterial pressure could not account for changes of release of ACTH. Several ACTH-active areas were defined. The anatomical relations of these areas with known nuclei and pathways then were considered. Two ACTH facilitatory areas and one ACTH inhibitory area were identified in the lateral aspect of the medial hypothalamus. The dorsal facilitatory area appears to be an extension of the lateral division of the dorsolongitudinal fasciculus and to extend medially to join the Fields of Forel, the ventral tegmental area of Tsai, and the parvocellular, paraventricular, and periventricular nuclei. The ACTH inhibitory area appears to be an extension of portions of the central tegmental tract and to extend medially to the posterior hypothalamic area and the dorsal hypothalamic area and ventrally toward the basal hypothalamus. The ventral ACTH facilitatory area appears to be coincident with the medial forebrain bundle and to extend anteroventrally and medially through the supraoptic decussation to the suprachiasmatic, ventromedial, dorsomedial, periventricular, infundibular, and premammillary nuclei. Stimulation of the median eminence led to increased release of ACTH. The results suggest that ascending pathways from the lower brainstem mediating control of ACTH project to discrete areas of the hypothalamus and then converge on the medial basal hypothalamus."}
{"id": "PMID:217664", "title": "The response of adenosine 3',5'-monophosphate to norepinephrine in the hypothalamus and pineal organ of female rats in proestrus or diestrus.", "content": "The response of cAMP to norepinephrine (NE) was measured in hypothalamic tissue and pineal glands of cycling female rats killed on the mornings of proestrus and diestrus (in 4-day cycles) or diestrus II (in 5-day cycles). The results from 4- or 5-day cycles were similar in all cases. The report of Weiss and Crayton that the response of adenylate cyclase in pineal homogenates to NE is reduced on proestrus was confirmed, and a similar but lesser reduction was also detected with intact pineal glands incubated in vitro. Chopped hypothalamic tissue incubated in vitro revealed a greater response of cAMP levels to NE on proestrus compared to diestrus in the anterior hypothalamic-preoptic area, but no significant changes in the middle or posterior hypothalamus. In an effort to reproduce the changes noted on proestrus, ovariectomized animals were injected with estradiol benzoate for 2 days, but no effects of the treatment on the cAMP response to NE were found. If the animals were also given reserpine, however, the estrogen was effective in reducing the response of pineal adenylate cyclase to NE. Possible explanations for these results and the potential significance of alterations in NE receptor systems for the control of gonadotropin release are discussed.", "contents": "The response of adenosine 3',5'-monophosphate to norepinephrine in the hypothalamus and pineal organ of female rats in proestrus or diestrus. The response of cAMP to norepinephrine (NE) was measured in hypothalamic tissue and pineal glands of cycling female rats killed on the mornings of proestrus and diestrus (in 4-day cycles) or diestrus II (in 5-day cycles). The results from 4- or 5-day cycles were similar in all cases. The report of Weiss and Crayton that the response of adenylate cyclase in pineal homogenates to NE is reduced on proestrus was confirmed, and a similar but lesser reduction was also detected with intact pineal glands incubated in vitro. Chopped hypothalamic tissue incubated in vitro revealed a greater response of cAMP levels to NE on proestrus compared to diestrus in the anterior hypothalamic-preoptic area, but no significant changes in the middle or posterior hypothalamus. In an effort to reproduce the changes noted on proestrus, ovariectomized animals were injected with estradiol benzoate for 2 days, but no effects of the treatment on the cAMP response to NE were found. If the animals were also given reserpine, however, the estrogen was effective in reducing the response of pineal adenylate cyclase to NE. Possible explanations for these results and the potential significance of alterations in NE receptor systems for the control of gonadotropin release are discussed."}
{"id": "PMID:217665", "title": "Alterations in insulin binding induced by changes in vivo in the levels of glucocorticoids and growth hormone.", "content": "Previous studies have shown that the sensitivity of tissues to insulin is diminished in states of glucocorticoid and GH excess and is increased when these hormones are deficient. To evaluate the role of the insulin receptor in these states, we have studied [125I]insulin binding to purified liver plasma membranes obtained from rats with a variety of perturbations of both glucocorticoids and GH. Glucocorticoid excess was produced in rats by administration of ACTH (40 U/day for 4 days) or dexamethasone (1 mg/day for 4 days). This resulted in an insulin-resistant state. Associated with this insulin resistance, there was a 50-60% decrease in insulin binding to its specific receptors in liver. Conversely, adrenalectomy, which produces an increase in insulin sensitivity, was associated with an increase in insulin binding to liver. Computer-assisted Scatchard analysis using a negative cooperative model for the inulin-receptor interaction indicated that, in contrast to our findings with obesity, the changes in insulin binding in these states were most likely due entirely to changes in receptor affinity, with no change in receptor concentration. GH administration also produced mild insulin resistance and a decrease in receptor concentration. This was associated with a reciprocal increase in receptor affinity and thus, no major alteration in insulin binding occurred at low physiological insulin concentrations. Hypophysectomized rats, on the other hand, showed an increase in receptor concentration and a decrease in affinity, and GH treatment only partially corrected these changes. Rats implanted with the MtT tumor (which secretes ACTH, GH, and PRL) have the combined effects of excess glucocorticoids and GH and are very insulin resistant. Liver membranes prepared from these rats showed a decrease in insulin binding and receptor affinity similar to that observed in other states of glucocorticoid excess. Further, adrenalectomy of the tumor-bearing rats resulted in an increase in insulin binding despite the persistence of the elevated levels of GH, ACTH, and PRL. These findings suggest that alterations in insulin receptor affinity and number may play a major role in the states of altered insulin sensitivity which accompany glucocorticoid excess and deficiency, and follow hypophysectomy. In contrast, the insulin resistance associated with GH excess is mediated at either a site on the receptor distal to the insulin-binding site (i.e. transduction) or at one or more of the intracellular reactions important in insulin action.", "contents": "Alterations in insulin binding induced by changes in vivo in the levels of glucocorticoids and growth hormone. Previous studies have shown that the sensitivity of tissues to insulin is diminished in states of glucocorticoid and GH excess and is increased when these hormones are deficient. To evaluate the role of the insulin receptor in these states, we have studied [125I]insulin binding to purified liver plasma membranes obtained from rats with a variety of perturbations of both glucocorticoids and GH. Glucocorticoid excess was produced in rats by administration of ACTH (40 U/day for 4 days) or dexamethasone (1 mg/day for 4 days). This resulted in an insulin-resistant state. Associated with this insulin resistance, there was a 50-60% decrease in insulin binding to its specific receptors in liver. Conversely, adrenalectomy, which produces an increase in insulin sensitivity, was associated with an increase in insulin binding to liver. Computer-assisted Scatchard analysis using a negative cooperative model for the inulin-receptor interaction indicated that, in contrast to our findings with obesity, the changes in insulin binding in these states were most likely due entirely to changes in receptor affinity, with no change in receptor concentration. GH administration also produced mild insulin resistance and a decrease in receptor concentration. This was associated with a reciprocal increase in receptor affinity and thus, no major alteration in insulin binding occurred at low physiological insulin concentrations. Hypophysectomized rats, on the other hand, showed an increase in receptor concentration and a decrease in affinity, and GH treatment only partially corrected these changes. Rats implanted with the MtT tumor (which secretes ACTH, GH, and PRL) have the combined effects of excess glucocorticoids and GH and are very insulin resistant. Liver membranes prepared from these rats showed a decrease in insulin binding and receptor affinity similar to that observed in other states of glucocorticoid excess. Further, adrenalectomy of the tumor-bearing rats resulted in an increase in insulin binding despite the persistence of the elevated levels of GH, ACTH, and PRL. These findings suggest that alterations in insulin receptor affinity and number may play a major role in the states of altered insulin sensitivity which accompany glucocorticoid excess and deficiency, and follow hypophysectomy. In contrast, the insulin resistance associated with GH excess is mediated at either a site on the receptor distal to the insulin-binding site (i.e. transduction) or at one or more of the intracellular reactions important in insulin action."}
{"id": "PMID:217667", "title": "Rat adrenal androgen receptor: a possible mediator of androgen-induced decreased in rat adrenal weight.", "content": "Many previous studies have demonstrated effects of gonadal steroids on adrenal weight in the rat. Most of these effects are indirect, depending upon alterations in the pituitary-adrenal axis for their expression. In this study we have attempted to examine the direct effects of gonadal steroids on adrenal weight in the rat. This was done using hypophysectomized, castrated male rats receiving ACTH replacement, a model which excludes pituitary-adrenal feedback effects. Estradiol-treated rats did not differ from controls, whereas testosterone-treated rats exhibited a small but statistically significant decrease in adrenal weight. As a first step in exploring the mechanism of this androgen effect, we have identified a specific dihydrotestosterone-binding protein in the rat adrenal gland. A single class of high affinity (Kd = 0.6-2.0 x 10(-8) M), saturable (28 fmol/mg cytosol protein), cytoplasmic binding sites was found using both protamine sulfate precipitation and dextran-coated charcoal assays. The specificity, sedimentation coefficient on sucrose gradient, and sensitivity to sulfhydryl reagents and heat of this dihydrotestosterone-binding protein are typical of the cytoplasmic androgen receptor from other androgen target tissues such as prostrate. We conclude that testosterone can decrease rat adrenal weight directly, and that the mechanism may involve a high affinity binding protein, as has been shown in other androgen-responsive systems.", "contents": "Rat adrenal androgen receptor: a possible mediator of androgen-induced decreased in rat adrenal weight. Many previous studies have demonstrated effects of gonadal steroids on adrenal weight in the rat. Most of these effects are indirect, depending upon alterations in the pituitary-adrenal axis for their expression. In this study we have attempted to examine the direct effects of gonadal steroids on adrenal weight in the rat. This was done using hypophysectomized, castrated male rats receiving ACTH replacement, a model which excludes pituitary-adrenal feedback effects. Estradiol-treated rats did not differ from controls, whereas testosterone-treated rats exhibited a small but statistically significant decrease in adrenal weight. As a first step in exploring the mechanism of this androgen effect, we have identified a specific dihydrotestosterone-binding protein in the rat adrenal gland. A single class of high affinity (Kd = 0.6-2.0 x 10(-8) M), saturable (28 fmol/mg cytosol protein), cytoplasmic binding sites was found using both protamine sulfate precipitation and dextran-coated charcoal assays. The specificity, sedimentation coefficient on sucrose gradient, and sensitivity to sulfhydryl reagents and heat of this dihydrotestosterone-binding protein are typical of the cytoplasmic androgen receptor from other androgen target tissues such as prostrate. We conclude that testosterone can decrease rat adrenal weight directly, and that the mechanism may involve a high affinity binding protein, as has been shown in other androgen-responsive systems."}
{"id": "PMID:217668", "title": "Evidence for activation by beta2-adrenergic receptors of adenosine 3',5'-monophosphate formation in Ehrlich ascites tumor cells.", "content": "The existence of aminergic receptors in mouse Ehrlich ascites tumor cells was studied. L-Isoproterenol in vitro stimulated the formation of cAMP in isolated Ehrlich ascites tumor cells. Stimulation by isoproterenol of cAMP formation was not significantly inhibited by practolol, a beta1-adrenoceptor antagonist-Salbutamol, a beta2-adrenoceptor agonist, markedly stimulated the formation of cAMP in Ehrlich ascites tumor cells at concentrations from 10(-8)-10(-3) M. After the addition of salbutamol, cAMP levels reached a maximum in 10 min and declined to about 2-fold of the basal level to 30 min. The stimulation by salbutamol of cAMP formation was markedly inhibited by butoxamine, a beta2-adrenoceptor antagonist, but not by practolol. Furthermore, the effect of a maximal dose of salbutamol was additive to that of prostaglandin E2. Histamine and 4-methylhistamine, a histamine H2 receptor agonist, had no significant effects. Therefore, it is suggested that a beta2-adrenergic receptor exists in the membranes of Ehrlich ascites tumor cells in terms of the adenylate cyclase-cAMP system.", "contents": "Evidence for activation by beta2-adrenergic receptors of adenosine 3',5'-monophosphate formation in Ehrlich ascites tumor cells. The existence of aminergic receptors in mouse Ehrlich ascites tumor cells was studied. L-Isoproterenol in vitro stimulated the formation of cAMP in isolated Ehrlich ascites tumor cells. Stimulation by isoproterenol of cAMP formation was not significantly inhibited by practolol, a beta1-adrenoceptor antagonist-Salbutamol, a beta2-adrenoceptor agonist, markedly stimulated the formation of cAMP in Ehrlich ascites tumor cells at concentrations from 10(-8)-10(-3) M. After the addition of salbutamol, cAMP levels reached a maximum in 10 min and declined to about 2-fold of the basal level to 30 min. The stimulation by salbutamol of cAMP formation was markedly inhibited by butoxamine, a beta2-adrenoceptor antagonist, but not by practolol. Furthermore, the effect of a maximal dose of salbutamol was additive to that of prostaglandin E2. Histamine and 4-methylhistamine, a histamine H2 receptor agonist, had no significant effects. Therefore, it is suggested that a beta2-adrenergic receptor exists in the membranes of Ehrlich ascites tumor cells in terms of the adenylate cyclase-cAMP system."}
{"id": "PMID:217669", "title": "Progressive suppression of adrenocorticotropin secretion in resting adrenalectomized dogs by low stepwise infusions of cortisol.", "content": "Ten male mongrel dogs of 8.3-14.3 kg were bilaterally adrenalectomized and maintained on replacement steroids for 1 week. No exogenous steroids were detectable at the time of the experiment. Each dog, under light Nembutal anesthesia, received two stepwise primed constant infusions of cortisol (iv), each lasting 90 min (except in one dog with three infusions of 60 min). A recovery period of 80 min without cortisol infusion followed. Twenty-three venous blood samples were withdrawn for determination of plasma ACTH by adrenal cell suspension bioassay and 25 were withdrawn for plasma cortisol by fluorimetry at various times before, during, and after the cortisol infusions. ACTH secretion rates were calculated continuously from functions fitted to ACTH concentration and time data, using a validated single compartment approach with previously determined clearances and volumes. Initial high ACTH secretion rates of 1.0 +/- 0.2 mU/kg . min (range, 0.3-2.4) were reduced by 67.4 +/- 4.6% and 94.6 +/- 2.1% by the two cortisol infusions, which yielded cortisol plateau concentrations in plasma of 4.24 +/- 0.41 and 6.09 +/- 0.68 microgram/100 ml, respectively. This sensitive feedback response to low cortisol concentrations was delayed, with no effect for about 20 min and maximal effect reached within 1 h. There was no evidence of a fast rate-sensitive feedback. Some increases in ACTH secretion were seen during the recovery period (errors are +/- SEM).", "contents": "Progressive suppression of adrenocorticotropin secretion in resting adrenalectomized dogs by low stepwise infusions of cortisol. Ten male mongrel dogs of 8.3-14.3 kg were bilaterally adrenalectomized and maintained on replacement steroids for 1 week. No exogenous steroids were detectable at the time of the experiment. Each dog, under light Nembutal anesthesia, received two stepwise primed constant infusions of cortisol (iv), each lasting 90 min (except in one dog with three infusions of 60 min). A recovery period of 80 min without cortisol infusion followed. Twenty-three venous blood samples were withdrawn for determination of plasma ACTH by adrenal cell suspension bioassay and 25 were withdrawn for plasma cortisol by fluorimetry at various times before, during, and after the cortisol infusions. ACTH secretion rates were calculated continuously from functions fitted to ACTH concentration and time data, using a validated single compartment approach with previously determined clearances and volumes. Initial high ACTH secretion rates of 1.0 +/- 0.2 mU/kg . min (range, 0.3-2.4) were reduced by 67.4 +/- 4.6% and 94.6 +/- 2.1% by the two cortisol infusions, which yielded cortisol plateau concentrations in plasma of 4.24 +/- 0.41 and 6.09 +/- 0.68 microgram/100 ml, respectively. This sensitive feedback response to low cortisol concentrations was delayed, with no effect for about 20 min and maximal effect reached within 1 h. There was no evidence of a fast rate-sensitive feedback. Some increases in ACTH secretion were seen during the recovery period (errors are +/- SEM)."}
{"id": "PMID:217670", "title": "Specific binding of iodinated growth hormone to rat liver in vivo.", "content": "The specific uptake by rat liver of human (hGH) and bovine (bGH) GHs labeled with 125I was studied by an in vivo procedure. A significant reduction of the uptake was observed when labeled hormones were injected together with different amounts of the corresponding native GH. This reduction was dose dependent, and the concentration of native hormone that prevents 50% of the liver uptake of the labeled hormone was close to 12 microgram/100 g BW. In normal rats, only native hGH or bGH significantly decreased the liver uptake of [125I]iodo-bGH, while bovine PRL (oPRL) or heat-denatured bGH were inactive. The highest inhibition of the uptake of [125I]iodo-hGH by rat liver was obtained when this labeled hormone was injected either together with hGH or with bGH plus oPRL while partial displacement was observed with bGH or oPRL. These data suggest that hGH binds to both somatotropic and lactogenic sites in the liver of normal rats. In hypophysectomized animals, only the somatogenic binding sites could be detected.", "contents": "Specific binding of iodinated growth hormone to rat liver in vivo. The specific uptake by rat liver of human (hGH) and bovine (bGH) GHs labeled with 125I was studied by an in vivo procedure. A significant reduction of the uptake was observed when labeled hormones were injected together with different amounts of the corresponding native GH. This reduction was dose dependent, and the concentration of native hormone that prevents 50% of the liver uptake of the labeled hormone was close to 12 microgram/100 g BW. In normal rats, only native hGH or bGH significantly decreased the liver uptake of [125I]iodo-bGH, while bovine PRL (oPRL) or heat-denatured bGH were inactive. The highest inhibition of the uptake of [125I]iodo-hGH by rat liver was obtained when this labeled hormone was injected either together with hGH or with bGH plus oPRL while partial displacement was observed with bGH or oPRL. These data suggest that hGH binds to both somatotropic and lactogenic sites in the liver of normal rats. In hypophysectomized animals, only the somatogenic binding sites could be detected."}
{"id": "PMID:217671", "title": "The contribution of local tissue thyroxine monodeiodination to the nuclear 3,5,3'-triiodothyronine in pituitary, liver, and kidney of euthyroid rats.", "content": "The contributions of local T4 monodeiodination and plasma T3 to the nuclear T3 of anterior pituitary, liver, and kidney were measured in euthyroid rats. After injection of [125I]T4, there was a gradual increase in the quantity of plasma [125I]T3 in excess of injected contaminant, which peaked at approximately 12 h after injection and remained a constant fraction of plasma [125I]T4 (2.8 X 10(-3) after that time. In the nuclei of anterior pituitary tissue, there was also a slow increase in locally produced [125I]T3 (in excess of that which could be accounted for by plasma [125I]T3) which appeared to peak at about 16 h after [125I]T4 administration. The ratio of nuclear [125I]T3 generated intracellularly to plasma [125I]T4 was constant at 18 and 24 h after T4 injection and was 13 +/- 2 X 10(-3) in nuclei of pituitary, 2.0 +/- 0.4 x 10(-3) in liver, and 0.47 +/- 0.1 x 10(-3) in kidney (all values are mean +/- SD). This locally generated T3 resulted in a markedly higher nuclear to plasma (N:P) ratio for [125I]T3 than for injected [131I]T3 in the same animals. The N:P ratio for [125I]T3 at equilibrium after injected T4 was 2.4 +/- 0.6, 0.47 +/- 0.09, and 0.10 +/- 0.03 (nanograms of T3 (mg DNA)-1/ng T3 ml-1) in pituitary, liver, and kidney. Comparable values for [131I]T3 N:P ratios were 0.47 +/- 0.14 (pituitary), 0.18 +/- 0.01 (liver), and 0.036 +/- 0.008 (kidney). Using RIA values for plasma T4 and T3 concentrations in these rats and maximal nuclear T3-binding capacities estimated in parallel experiments, the gravimetric quantities of nuclear T3 derived from plasma T3 and from local T4 to T3 monodeiodination were estimated and expressed as the percentage of saturation of T3 receptors. Seventy-eight percent of nuclear T3 receptor sites in anterior pituitary were occupied with one-half of the nuclear T3 derived directly from plasma T3 and the other half from intrapituitary T4 monodeiodination. Local T4 monodeiodination provided only 28% and 14%, respectively, of the nuclear T3 in liver and kidney, and the nuclear receptors of these tissues were about 50% saturated. Since our previous studies have shown that the occupancy of the pituitary nuclear T3 receptors may regulate TSH release, these data provide a mechanism by which TSH secretion could be altered by changes in either plasma T3 or T4, whereas nuclear T3 in liver and kidney is predominantly a function of the plasma T3 concentration.", "contents": "The contribution of local tissue thyroxine monodeiodination to the nuclear 3,5,3'-triiodothyronine in pituitary, liver, and kidney of euthyroid rats. The contributions of local T4 monodeiodination and plasma T3 to the nuclear T3 of anterior pituitary, liver, and kidney were measured in euthyroid rats. After injection of [125I]T4, there was a gradual increase in the quantity of plasma [125I]T3 in excess of injected contaminant, which peaked at approximately 12 h after injection and remained a constant fraction of plasma [125I]T4 (2.8 X 10(-3) after that time. In the nuclei of anterior pituitary tissue, there was also a slow increase in locally produced [125I]T3 (in excess of that which could be accounted for by plasma [125I]T3) which appeared to peak at about 16 h after [125I]T4 administration. The ratio of nuclear [125I]T3 generated intracellularly to plasma [125I]T4 was constant at 18 and 24 h after T4 injection and was 13 +/- 2 X 10(-3) in nuclei of pituitary, 2.0 +/- 0.4 x 10(-3) in liver, and 0.47 +/- 0.1 x 10(-3) in kidney (all values are mean +/- SD). This locally generated T3 resulted in a markedly higher nuclear to plasma (N:P) ratio for [125I]T3 than for injected [131I]T3 in the same animals. The N:P ratio for [125I]T3 at equilibrium after injected T4 was 2.4 +/- 0.6, 0.47 +/- 0.09, and 0.10 +/- 0.03 (nanograms of T3 (mg DNA)-1/ng T3 ml-1) in pituitary, liver, and kidney. Comparable values for [131I]T3 N:P ratios were 0.47 +/- 0.14 (pituitary), 0.18 +/- 0.01 (liver), and 0.036 +/- 0.008 (kidney). Using RIA values for plasma T4 and T3 concentrations in these rats and maximal nuclear T3-binding capacities estimated in parallel experiments, the gravimetric quantities of nuclear T3 derived from plasma T3 and from local T4 to T3 monodeiodination were estimated and expressed as the percentage of saturation of T3 receptors. Seventy-eight percent of nuclear T3 receptor sites in anterior pituitary were occupied with one-half of the nuclear T3 derived directly from plasma T3 and the other half from intrapituitary T4 monodeiodination. Local T4 monodeiodination provided only 28% and 14%, respectively, of the nuclear T3 in liver and kidney, and the nuclear receptors of these tissues were about 50% saturated. Since our previous studies have shown that the occupancy of the pituitary nuclear T3 receptors may regulate TSH release, these data provide a mechanism by which TSH secretion could be altered by changes in either plasma T3 or T4, whereas nuclear T3 in liver and kidney is predominantly a function of the plasma T3 concentration."}
{"id": "PMID:217672", "title": "16-Hydroxylation of estrone-3-sulfate and estrone in the guinea pig in vivo.", "content": "[6,7-3H]Estrone-3-sulfate or [6,7-3H]-estrone of high specific activity was injected into adult female English Shorthair guinea pigs. Blood, liver, kidney, gall bladder bile, and urine were obtained and investigated for metabolites. Chromatographic procedures followed by enzymatic or solvolytic cleavage of conjugates and subsequent crystallization with appropriate carrier steroids revealed the pattern of metabolites formed. Injected estrone sulfate was partially hydrolyzed and reconjugated, resulting in the production of estrone and estradiol glucuronides. The main metabolites, however, were monosulfates of 16alpha-hydroxyestrone, 16-keto-17beta-estradiol, and estriol as well as disulfates of 16alpha-hydroxyestrone, estriol, and 16beta-hydroxyestrone. Particularly high amounts of these were found in urine. By far the main metabolites of injected estrone were glucuronides of estrone and estradiol, although the pattern of mono- and disulfated steroids was qualitatively similar to that found after estrone sulfate injection. It is concluded that the guinea pigs employed in the study hydroxylated estrogen in the 16alpha- and 16beta-configurations and that this activity was much more pronounced after injection of estrone sulfate than after estrone.", "contents": "16-Hydroxylation of estrone-3-sulfate and estrone in the guinea pig in vivo. [6,7-3H]Estrone-3-sulfate or [6,7-3H]-estrone of high specific activity was injected into adult female English Shorthair guinea pigs. Blood, liver, kidney, gall bladder bile, and urine were obtained and investigated for metabolites. Chromatographic procedures followed by enzymatic or solvolytic cleavage of conjugates and subsequent crystallization with appropriate carrier steroids revealed the pattern of metabolites formed. Injected estrone sulfate was partially hydrolyzed and reconjugated, resulting in the production of estrone and estradiol glucuronides. The main metabolites, however, were monosulfates of 16alpha-hydroxyestrone, 16-keto-17beta-estradiol, and estriol as well as disulfates of 16alpha-hydroxyestrone, estriol, and 16beta-hydroxyestrone. Particularly high amounts of these were found in urine. By far the main metabolites of injected estrone were glucuronides of estrone and estradiol, although the pattern of mono- and disulfated steroids was qualitatively similar to that found after estrone sulfate injection. It is concluded that the guinea pigs employed in the study hydroxylated estrogen in the 16alpha- and 16beta-configurations and that this activity was much more pronounced after injection of estrone sulfate than after estrone."}
{"id": "PMID:217676", "title": "Studies on cyclic nucleotides in the adrenal gland. VIII. Effects of angiotensin on adenosine 3',5'-monophosphate and steroidogenesis in the adrenal cortex.", "content": "Effects of angiotensin II on corticoid biogenesis and cAMP levels in the zona fasciculata-reticularis (the decapsulated fraction) and the zona glomerulosa (the capsular fraction) from the rat adrenal gland have been studied. Angiotensin II exclusively stimulated steroidogenesis in the zona glomerulosa without stimulation of the cAMP system, suggesting that steroidogenic action of this polypeptide does not involve the adenylate cyclase system. Angiotensin II was also found to stimulate cAMP-phosphodiesterase activity in the zona glomerulosa. An elevation of calcium concentration in the incubation medium has been observed to be effective in stimulating the production of aldosterone and cAMP by the capsular fraction. Angiotensin II caused a significant enhancement of the steroidogenic response of the capsular fraction to increasing calcium concentration regardless of the response of the cAMP system to calcium. This steroidogenic effect of angiotensin II was completely abolished by calcium antagonists added to the incubation medium without any inhibitory effect on the calcium-induced accumulation of tissue cAMP. These results suggest that angiotensin II acts on the adrenal II acts on the adrenal glomerulosa cell to increase intracellular calcium, which in turn directly stimulates steroidogenesis concomitant with the increased activity of phosphodiesterase.", "contents": "Studies on cyclic nucleotides in the adrenal gland. VIII. Effects of angiotensin on adenosine 3',5'-monophosphate and steroidogenesis in the adrenal cortex. Effects of angiotensin II on corticoid biogenesis and cAMP levels in the zona fasciculata-reticularis (the decapsulated fraction) and the zona glomerulosa (the capsular fraction) from the rat adrenal gland have been studied. Angiotensin II exclusively stimulated steroidogenesis in the zona glomerulosa without stimulation of the cAMP system, suggesting that steroidogenic action of this polypeptide does not involve the adenylate cyclase system. Angiotensin II was also found to stimulate cAMP-phosphodiesterase activity in the zona glomerulosa. An elevation of calcium concentration in the incubation medium has been observed to be effective in stimulating the production of aldosterone and cAMP by the capsular fraction. Angiotensin II caused a significant enhancement of the steroidogenic response of the capsular fraction to increasing calcium concentration regardless of the response of the cAMP system to calcium. This steroidogenic effect of angiotensin II was completely abolished by calcium antagonists added to the incubation medium without any inhibitory effect on the calcium-induced accumulation of tissue cAMP. These results suggest that angiotensin II acts on the adrenal II acts on the adrenal glomerulosa cell to increase intracellular calcium, which in turn directly stimulates steroidogenesis concomitant with the increased activity of phosphodiesterase."}
{"id": "PMID:217678", "title": "Studies on the metabolism of steroid hormones in a virilizing adrenal cortex adenoma.", "content": "Slices of an adreno-cortical adenoma which had been obtained at operation from an 11-year-old girl with clinical signs of virilism were incubated with each of the following steroids: [1,2-3H]progesterone, [4-14C]pregnenolone, [1,2-3H]testosterone, [4-14C]androstenedione and [7-3H]dehydroepiandrosterone, respectively. Isolation and identification of the free radioactive metabolites were achieved by gel column chromatography on Sephadex LH-20, thin-layer chromatography, radio gas chromatography and isotope dilution. After incubation of progesterone, the following metabolites were identified: 11beta-hydroxyprogesterone, 16alpha-hydroxyprogesterone, 17alpha-hydroxyprogesterone, 21-deoxycortisol, corticosterone and cortisol. Pregnenolone was metabolized to 17alpha-hydroxypregnenolone, progesterone, dehydroepiandrosterone, androstenedione and 11beta-hydroxyandrostenedione. When testosterone was used as substrate, 11beta-hydroxytestosterone, androstenedione and 11beta-hydroxyandrostenedione were found as metabolites, whereas androstenedione was metabolized to testosterone and 11beta-hydroxyandrostenedione. After incubation of dehydroepiandrosterone, only androstenedione and 11beta-hydroxyandrostenedione were isolated and identified. From these results, it appears that cortisol was formed in the adenoma tissue via 21-deoxycortisol and corticosterone. Delta4-3oxo steroids of the C19-series arose exclusively from pregnenolone via 17alpha-hydroxypregnenolone and dehydroepiandrosterone, and not from progesterone and 17alpha-hydroxyprogesterone. Calculated on the amounts of metabolites formed, the highest enzyme activities were those of the 11beta-hydroxylase and the 17alpha-hydroxylase. It is interesting to note that only traces of testosterone were detected after incubation of androstenedione, whereas testosterone yielded large amounts of androstenedione.", "contents": "Studies on the metabolism of steroid hormones in a virilizing adrenal cortex adenoma. Slices of an adreno-cortical adenoma which had been obtained at operation from an 11-year-old girl with clinical signs of virilism were incubated with each of the following steroids: [1,2-3H]progesterone, [4-14C]pregnenolone, [1,2-3H]testosterone, [4-14C]androstenedione and [7-3H]dehydroepiandrosterone, respectively. Isolation and identification of the free radioactive metabolites were achieved by gel column chromatography on Sephadex LH-20, thin-layer chromatography, radio gas chromatography and isotope dilution. After incubation of progesterone, the following metabolites were identified: 11beta-hydroxyprogesterone, 16alpha-hydroxyprogesterone, 17alpha-hydroxyprogesterone, 21-deoxycortisol, corticosterone and cortisol. Pregnenolone was metabolized to 17alpha-hydroxypregnenolone, progesterone, dehydroepiandrosterone, androstenedione and 11beta-hydroxyandrostenedione. When testosterone was used as substrate, 11beta-hydroxytestosterone, androstenedione and 11beta-hydroxyandrostenedione were found as metabolites, whereas androstenedione was metabolized to testosterone and 11beta-hydroxyandrostenedione. After incubation of dehydroepiandrosterone, only androstenedione and 11beta-hydroxyandrostenedione were isolated and identified. From these results, it appears that cortisol was formed in the adenoma tissue via 21-deoxycortisol and corticosterone. Delta4-3oxo steroids of the C19-series arose exclusively from pregnenolone via 17alpha-hydroxypregnenolone and dehydroepiandrosterone, and not from progesterone and 17alpha-hydroxyprogesterone. Calculated on the amounts of metabolites formed, the highest enzyme activities were those of the 11beta-hydroxylase and the 17alpha-hydroxylase. It is interesting to note that only traces of testosterone were detected after incubation of androstenedione, whereas testosterone yielded large amounts of androstenedione."}
{"id": "PMID:217679", "title": "Specificity of action of neuraminidase, according to its bacteriological origin.", "content": "Neuraminidase from Vibrio Cholerae selectively cleaves sialic acid from FSH, but leaves the LH sialic acid, not influencing the biological activity of the latter hormone. On the other hand, Neuraminidase from Clostridium perfringens does not possess this specific action and destroys the biological activity of LH as is suggested by Parlow's OAAD-test.", "contents": "Specificity of action of neuraminidase, according to its bacteriological origin. Neuraminidase from Vibrio Cholerae selectively cleaves sialic acid from FSH, but leaves the LH sialic acid, not influencing the biological activity of the latter hormone. On the other hand, Neuraminidase from Clostridium perfringens does not possess this specific action and destroys the biological activity of LH as is suggested by Parlow's OAAD-test."}
{"id": "PMID:217680", "title": "Antiepileptic drugs and vitamin D supplementation.", "content": "The incidence of biochemical signs of vitamin D deficiency and the effects of vitamin D supplementation were investigated in 83 children and 95 adults on chronic antiepileptic therapy and 40 mentally retarded controls living under comparable conditions. Low 25-hydroxyvitamin D and serum calcium, and elevated immunoreactive parathyroid hormone and alkaline phosphatase was a common finding in all groups, but in patients on antiepileptic drugs, signs of vitamin D deficiency were recorded more frequently. Supplementation of 125 microgram or 250 microgram vitamin D3 per week for 9 months normalized the laboratory findings in most patients; the effect of 37.5 microgram/week only slightly exceeded the influences of season observed in the controls and in epileptic patients without vitamin D. It is suggested that a dose between 37.5 and 125 microgram vitamin D3/week might be most suitable to avoid biochemical signs of vitamin D deficiency in children and adults on antiepileptic drugs.", "contents": "Antiepileptic drugs and vitamin D supplementation. The incidence of biochemical signs of vitamin D deficiency and the effects of vitamin D supplementation were investigated in 83 children and 95 adults on chronic antiepileptic therapy and 40 mentally retarded controls living under comparable conditions. Low 25-hydroxyvitamin D and serum calcium, and elevated immunoreactive parathyroid hormone and alkaline phosphatase was a common finding in all groups, but in patients on antiepileptic drugs, signs of vitamin D deficiency were recorded more frequently. Supplementation of 125 microgram or 250 microgram vitamin D3 per week for 9 months normalized the laboratory findings in most patients; the effect of 37.5 microgram/week only slightly exceeded the influences of season observed in the controls and in epileptic patients without vitamin D. It is suggested that a dose between 37.5 and 125 microgram vitamin D3/week might be most suitable to avoid biochemical signs of vitamin D deficiency in children and adults on antiepileptic drugs."}
{"id": "PMID:217681", "title": "Translation of alfalfa-mosaic-virus RNA 1 in the mRNA-dependent translation system from rabbit reticulocyte lysates.", "content": "Translation of alfalfa mosaic virus (AMV) RNAs in the mRNA-dependent rabbit reticulocyte cell-free system was examined using different RNA concentrations. The pattern of products synthesized under the direction of AMV RNA 2, 3 and 4 was not or almost not influenced by their concentration. However, depending on the RNA 1 concentration either a very large protein of Mr 115,000 or a mixture of two smaller proteins, Mr 58,000 and 62,000 respectively, was formed. These three proteins represent overlapping peptide chains with identical N-termini. Addition of the cap analogue 7-methylguanosine 5'-monophosphate (m7GMP) or AMV RNA 3 stimulated the production of the 115,000-Mr protein at the expense of the 58,000-Mr and 62,000-Mr proteins. Both m7GMP and RNA 3 probably reduce the active concentration of RNA 1 by competing for (a) cellular component(s) necessary for translation. These experimental results suggest that the rate of translation beyond the C termini of the 58,000-Mr and 62,000-Mr proteins is reduced or completely inhibited owing to the limited availability of the succeeding tRNA(s).", "contents": "Translation of alfalfa-mosaic-virus RNA 1 in the mRNA-dependent translation system from rabbit reticulocyte lysates. Translation of alfalfa mosaic virus (AMV) RNAs in the mRNA-dependent rabbit reticulocyte cell-free system was examined using different RNA concentrations. The pattern of products synthesized under the direction of AMV RNA 2, 3 and 4 was not or almost not influenced by their concentration. However, depending on the RNA 1 concentration either a very large protein of Mr 115,000 or a mixture of two smaller proteins, Mr 58,000 and 62,000 respectively, was formed. These three proteins represent overlapping peptide chains with identical N-termini. Addition of the cap analogue 7-methylguanosine 5'-monophosphate (m7GMP) or AMV RNA 3 stimulated the production of the 115,000-Mr protein at the expense of the 58,000-Mr and 62,000-Mr proteins. Both m7GMP and RNA 3 probably reduce the active concentration of RNA 1 by competing for (a) cellular component(s) necessary for translation. These experimental results suggest that the rate of translation beyond the C termini of the 58,000-Mr and 62,000-Mr proteins is reduced or completely inhibited owing to the limited availability of the succeeding tRNA(s)."}
{"id": "PMID:217685", "title": "Effects of spin-labeled stearates on duck erythrocyte adenylate cyclase.", "content": "The effects of various spin-labeled stearates on duck erythrocyte adenylate cyclase were investigated. Only 2-(3-carboxypropyl)-4,4-dimethyl-2-tridecyl-3-oxazolidinyloxyl caused an increase in adenylate cyclase activity. It increased the basal rate by about 50%, and the activities stimulated by isoproterenol and isoproterenol plus guanosine 5'-[beta,gamma-imido]triphosphate by 35%. Upon analysis of the width parameter delta1 in the electron spin resonance spectra for both the basal enzyme activity and the stimulation obtained with effectors such as guanosine 5'-[beta,gamma-imido]triphosphate, isoproterenol, isoproterenol plus guanosine 5'-[beta,gamma-imido]triphosphate and NaF, a correlation of the changes of modification in adenylate cyclase activities was found. These findings suggest that the molecular environment of the enzyme has been modified.", "contents": "Effects of spin-labeled stearates on duck erythrocyte adenylate cyclase. The effects of various spin-labeled stearates on duck erythrocyte adenylate cyclase were investigated. Only 2-(3-carboxypropyl)-4,4-dimethyl-2-tridecyl-3-oxazolidinyloxyl caused an increase in adenylate cyclase activity. It increased the basal rate by about 50%, and the activities stimulated by isoproterenol and isoproterenol plus guanosine 5'-[beta,gamma-imido]triphosphate by 35%. Upon analysis of the width parameter delta1 in the electron spin resonance spectra for both the basal enzyme activity and the stimulation obtained with effectors such as guanosine 5'-[beta,gamma-imido]triphosphate, isoproterenol, isoproterenol plus guanosine 5'-[beta,gamma-imido]triphosphate and NaF, a correlation of the changes of modification in adenylate cyclase activities was found. These findings suggest that the molecular environment of the enzyme has been modified."}
{"id": "PMID:217686", "title": "Parathyroid hormone and calcitonin levels in vitamin D deficient rickets.", "content": "In six infants aged between 5 and 8 months with vitamin D deficient rickets, we have studied blood levels of calcium (Ca), phosphorus (P), alkaline phosphatase, immunoreactive parathyroid hormone (PTH) and calcitonin (CT), as well as urinary excretion of Ca, P, hydroxyproline and cyclic AMP, both under basal conditions and during a 4h infusion of 20 mg/kg 10% Ca gluconate in normal saline. Under basal conditions all the infants had high alkaline phosphatase (range: 470--770 U.I./1); PTH (range: 620--1200 pg Eq/ml) and CT (range: 440--750 pg/ml) but two infants had hypocalcaemia and four had normocalcaemia and hypophosphataemia. The urinary Ca excretion was low whereas the urinary P, hydroxyproline and cyclic AMP excretions were high. During Ca infusion the total serum Ca and CT levels increased, while alkaline phosphatase and PTH fell. After the end of the infusion, CT levels fell perceptibly; phosphaturia, hydroxyprolinuria and cyclic AMP decreased on the day of the infusion.", "contents": "Parathyroid hormone and calcitonin levels in vitamin D deficient rickets. In six infants aged between 5 and 8 months with vitamin D deficient rickets, we have studied blood levels of calcium (Ca), phosphorus (P), alkaline phosphatase, immunoreactive parathyroid hormone (PTH) and calcitonin (CT), as well as urinary excretion of Ca, P, hydroxyproline and cyclic AMP, both under basal conditions and during a 4h infusion of 20 mg/kg 10% Ca gluconate in normal saline. Under basal conditions all the infants had high alkaline phosphatase (range: 470--770 U.I./1); PTH (range: 620--1200 pg Eq/ml) and CT (range: 440--750 pg/ml) but two infants had hypocalcaemia and four had normocalcaemia and hypophosphataemia. The urinary Ca excretion was low whereas the urinary P, hydroxyproline and cyclic AMP excretions were high. During Ca infusion the total serum Ca and CT levels increased, while alkaline phosphatase and PTH fell. After the end of the infusion, CT levels fell perceptibly; phosphaturia, hydroxyprolinuria and cyclic AMP decreased on the day of the infusion."}
{"id": "PMID:217687", "title": "Prolactin-producing pituitary adenoma in a 9 year old boy.", "content": "A boy aged 9 years and 8 months was evaluated for headache and an enlarged sella. His neurological status and visual fields were normal. After injection of radiographic contrast agent, computerized axial tomography showed evidence of an intrasellar tumor. The most striking endocrine abnormalities were growth hormone insufficiency after arginine infusion and after insulin-induced hypoglycemia, and excessively elevated prolactin levels ranging between 1220 ng/ml and 1560 ng/ml. A slightly granulated, acidophilic pituitary adenoma was selectively removed by the trans-sphenoidal approach. The function of the anterior pituitary improved post-operatively. Growth hormone secretion after insulin-induced hypoglycemia returned to normal, and the basal serum prolactin levels decreased, but are still three times higher than normal.", "contents": "Prolactin-producing pituitary adenoma in a 9 year old boy. A boy aged 9 years and 8 months was evaluated for headache and an enlarged sella. His neurological status and visual fields were normal. After injection of radiographic contrast agent, computerized axial tomography showed evidence of an intrasellar tumor. The most striking endocrine abnormalities were growth hormone insufficiency after arginine infusion and after insulin-induced hypoglycemia, and excessively elevated prolactin levels ranging between 1220 ng/ml and 1560 ng/ml. A slightly granulated, acidophilic pituitary adenoma was selectively removed by the trans-sphenoidal approach. The function of the anterior pituitary improved post-operatively. Growth hormone secretion after insulin-induced hypoglycemia returned to normal, and the basal serum prolactin levels decreased, but are still three times higher than normal."}
{"id": "PMID:217693", "title": "Humoral hypercalcaemia in a patient with renal-cell carcinoma.", "content": "In a patient with hypercalcaemia secondary to a renal-cell carcinoma, a concentration gradient of bioactivity was detected between the tumour effluent vein and the peripheral venous blood that was capable of stimulating adenylate cyclase in bone cells. Immuno-reactive PTH was undetectable in the tumour effluent and in the peripheral blood. It is concluded that a non-parathyroid humoral factor whose action involved cyclic AMP stimulation was responsible for the hypercalcaemia.", "contents": "Humoral hypercalcaemia in a patient with renal-cell carcinoma. In a patient with hypercalcaemia secondary to a renal-cell carcinoma, a concentration gradient of bioactivity was detected between the tumour effluent vein and the peripheral venous blood that was capable of stimulating adenylate cyclase in bone cells. Immuno-reactive PTH was undetectable in the tumour effluent and in the peripheral blood. It is concluded that a non-parathyroid humoral factor whose action involved cyclic AMP stimulation was responsible for the hypercalcaemia."}
{"id": "PMID:217694", "title": "Effect of polyenyl phosphatidyl choline on clofibrate-induced increase in LDL cholesterol.", "content": "In a double-blind, randomised, cross-over trial clofibrate and a combination of polyenyl phosphatidyl choline (PPC) plus clofibrate were tested in 67 patients with hyperlipoproteinemia. Each treatment lasted for 4 weeks and was separated by a 4 week placebo period. The daily doses were clofibrate 1.2 g and PPC 1.8 g + clofibrate 1.2 g. respectively. The results revealed that polypenyl phosphatidyl choline prevented the elevation of LDL-cholesterol induced by clofibrate treatment, and that the lipid-lowering potency of the combination did not differ significantly from that of clofibrate. Since elevation of LDL-cholesterol is considered to increase the risk of coronary heart disease, the combination appears to offer a therapeutic advantage. Despite the significance of this clinical observation, a final decision may only be obtained from a prospective, long term investigation in patients with coronary heart diseases and hyperlipoproteinemia.", "contents": "Effect of polyenyl phosphatidyl choline on clofibrate-induced increase in LDL cholesterol. In a double-blind, randomised, cross-over trial clofibrate and a combination of polyenyl phosphatidyl choline (PPC) plus clofibrate were tested in 67 patients with hyperlipoproteinemia. Each treatment lasted for 4 weeks and was separated by a 4 week placebo period. The daily doses were clofibrate 1.2 g and PPC 1.8 g + clofibrate 1.2 g. respectively. The results revealed that polypenyl phosphatidyl choline prevented the elevation of LDL-cholesterol induced by clofibrate treatment, and that the lipid-lowering potency of the combination did not differ significantly from that of clofibrate. Since elevation of LDL-cholesterol is considered to increase the risk of coronary heart disease, the combination appears to offer a therapeutic advantage. Despite the significance of this clinical observation, a final decision may only be obtained from a prospective, long term investigation in patients with coronary heart diseases and hyperlipoproteinemia."}
{"id": "PMID:217696", "title": "Effects of adenosine on neurally mediated norepinephrine release from the cat spleen.", "content": "The effects of adenosine on the release of 3H-norepinephrine (3H-NE) from the isolated, perfused cat spleen consequent to nerve stimulation were evaluated. Electrical stimulation of the splenic nerve (5 Hz/100 impulses total) caused a release of 3H-NE and a rise in perfusion pressure. Adenosine added to the perfusion fluid (final concentrations 1 X 10(-6), 1 X 10(-5), and 1 X 10(-4) M) significantly reduced the pressure response elicited by nerve stimulation. In addition, adenosine (1 X 10(-4) M) slightly increased the release of total 3H consequent to nerve stimulation. Theophylline (1 X 10(-4) M) produced both a slight increase in the release of total 3H and a diminished pressure response. The effects of adenosine were effectively antagonized by this concentration of theophylline. Neither substance had any effect on the spontaneous release of total 3H. Adenosine (1 X 10(-4) M) also antagonized the pressure response elicited by perfusion of NE.", "contents": "Effects of adenosine on neurally mediated norepinephrine release from the cat spleen. The effects of adenosine on the release of 3H-norepinephrine (3H-NE) from the isolated, perfused cat spleen consequent to nerve stimulation were evaluated. Electrical stimulation of the splenic nerve (5 Hz/100 impulses total) caused a release of 3H-NE and a rise in perfusion pressure. Adenosine added to the perfusion fluid (final concentrations 1 X 10(-6), 1 X 10(-5), and 1 X 10(-4) M) significantly reduced the pressure response elicited by nerve stimulation. In addition, adenosine (1 X 10(-4) M) slightly increased the release of total 3H consequent to nerve stimulation. Theophylline (1 X 10(-4) M) produced both a slight increase in the release of total 3H and a diminished pressure response. The effects of adenosine were effectively antagonized by this concentration of theophylline. Neither substance had any effect on the spontaneous release of total 3H. Adenosine (1 X 10(-4) M) also antagonized the pressure response elicited by perfusion of NE."}
{"id": "PMID:217697", "title": "The natural tolerance of the afghan pika (Ochotona rufescens) to morphine.", "content": "A lagomorph, the afghan pika, Ochotona rufescens showed no effect whatever following the subcutaneous injection of morphine in doses up to 50 mg per 100 g of body weight, i.e. 250 times the ED50 for the rat. Higher doses were toxic and induced convulsions. However, the pika is responsive to synthetic opiates such as etorphine, pentazocine and phenoperidine. Interestingly enough, morphine antagonized the opiate response elicited by those narcotics to which the animal is sensitive. Pharmacokinetic analysis demonstrated that morphine enters the pika's brain as readily as it does the rat's. In addition, opiate receptor sites, which are present in normal amounts in pika brain retained their high affinity for 3H-etorphine (KD = 0.3 nM), 3H-naloxone (KD = 1.2 nM) and morphine. Moreover, binding of morphine to pika brain homogenates was inhibited in the presence of sodium ions (agonist response). Therefore, the antagonism of phenoperidine action by morphine appeared not to occur at the opiate receptor site; the mechanism of the pika's natural tolerance to morphine may reside in molecular events that normally preceed (metabolism?) or follow (enzyme activation?) the interaction between the drug and its specific recognition sites.", "contents": "The natural tolerance of the afghan pika (Ochotona rufescens) to morphine. A lagomorph, the afghan pika, Ochotona rufescens showed no effect whatever following the subcutaneous injection of morphine in doses up to 50 mg per 100 g of body weight, i.e. 250 times the ED50 for the rat. Higher doses were toxic and induced convulsions. However, the pika is responsive to synthetic opiates such as etorphine, pentazocine and phenoperidine. Interestingly enough, morphine antagonized the opiate response elicited by those narcotics to which the animal is sensitive. Pharmacokinetic analysis demonstrated that morphine enters the pika's brain as readily as it does the rat's. In addition, opiate receptor sites, which are present in normal amounts in pika brain retained their high affinity for 3H-etorphine (KD = 0.3 nM), 3H-naloxone (KD = 1.2 nM) and morphine. Moreover, binding of morphine to pika brain homogenates was inhibited in the presence of sodium ions (agonist response). Therefore, the antagonism of phenoperidine action by morphine appeared not to occur at the opiate receptor site; the mechanism of the pika's natural tolerance to morphine may reside in molecular events that normally preceed (metabolism?) or follow (enzyme activation?) the interaction between the drug and its specific recognition sites."}
{"id": "PMID:217698", "title": "Inhibition of nigral and neocortical cells by gamma-hydroxybutyrate: a microiontophoretic investigation.", "content": "gamma-Hydroxybutyrate (GHB) and gamma-aminobutyrate (GABA) were applied microiontophoretically near spontaneously active cells in the substantia nigra and the neocortex of chloral hydrate-anaesthetized rats. Whereas GABA in \"low doses\" (i.e. 20 nA ejection currents) depressed the activity of cells in both areas, GBH reduced the firing rate only when the compound was expelled with two to three times higher ejection currents. Under these conditions GHB depressed about half of the nigral but the majority of the neocortical cells tested. The depressant action of GABA was readily antagonized by microiontophoretic bicuculline methiodide whereas the effects of GHB were resistant to this alkaloid. Intraperitoneally administered GHB in doses of 300 and 600 mg/kg reduced the firing rate of the majority of spontaneously active neocortical cells. In conclusion, GHB inhibits the firing of nigral and neocortical neurons. However its effects are not mediated through the activation of bicuculline-sensitive GABA receptors.", "contents": "Inhibition of nigral and neocortical cells by gamma-hydroxybutyrate: a microiontophoretic investigation. gamma-Hydroxybutyrate (GHB) and gamma-aminobutyrate (GABA) were applied microiontophoretically near spontaneously active cells in the substantia nigra and the neocortex of chloral hydrate-anaesthetized rats. Whereas GABA in \"low doses\" (i.e. 20 nA ejection currents) depressed the activity of cells in both areas, GBH reduced the firing rate only when the compound was expelled with two to three times higher ejection currents. Under these conditions GHB depressed about half of the nigral but the majority of the neocortical cells tested. The depressant action of GABA was readily antagonized by microiontophoretic bicuculline methiodide whereas the effects of GHB were resistant to this alkaloid. Intraperitoneally administered GHB in doses of 300 and 600 mg/kg reduced the firing rate of the majority of spontaneously active neocortical cells. In conclusion, GHB inhibits the firing of nigral and neocortical neurons. However its effects are not mediated through the activation of bicuculline-sensitive GABA receptors."}
{"id": "PMID:217699", "title": "Mechanism of quasi-morphine withdrawal behaviour induced by methylxanthines.", "content": "Of 7 phosphodiesterase inhibitors tested for ability to induce a quasi-morphine withdrawal syndrome (QMWS) in opiate-naive rats, five were effective in a dose-related way. These, in descending order of potency, were IBMX, ICI-63197, RO-201724, theophylline and caffeine. Their potencies in inducing a QMWS correlated significantly (P less than 0.05) with those in inhibiting low Km cyclic AMP phosphodiesterase of rat brain homogenate. There was no correlation with potencies in inhibiting cyclic GMP phosphodiesterase.", "contents": "Mechanism of quasi-morphine withdrawal behaviour induced by methylxanthines. Of 7 phosphodiesterase inhibitors tested for ability to induce a quasi-morphine withdrawal syndrome (QMWS) in opiate-naive rats, five were effective in a dose-related way. These, in descending order of potency, were IBMX, ICI-63197, RO-201724, theophylline and caffeine. Their potencies in inducing a QMWS correlated significantly (P less than 0.05) with those in inhibiting low Km cyclic AMP phosphodiesterase of rat brain homogenate. There was no correlation with potencies in inhibiting cyclic GMP phosphodiesterase."}
{"id": "PMID:217700", "title": "Effects of intravenous baclofen on dorsal horn neurons of spinal cats.", "content": "Intravenous baclofen (1 mg/kg) abolished or severely attenuated the high threshold late component (but not the low threshold early component of long duration (greater than 150 msec) discharges evoked in cat dorsal horn neurons by intense transcutaneous electrical stimulation. Baclofen similarly reduced the spontaneous activities and discharges evoked by intra-arterial bradykinin in these same cells. These powerful inhibitions of dorsal horn interneurons may be the basis of baclofen's reported analgesic actions and could contribute to depression in reflex excitability of motoneurons.", "contents": "Effects of intravenous baclofen on dorsal horn neurons of spinal cats. Intravenous baclofen (1 mg/kg) abolished or severely attenuated the high threshold late component (but not the low threshold early component of long duration (greater than 150 msec) discharges evoked in cat dorsal horn neurons by intense transcutaneous electrical stimulation. Baclofen similarly reduced the spontaneous activities and discharges evoked by intra-arterial bradykinin in these same cells. These powerful inhibitions of dorsal horn interneurons may be the basis of baclofen's reported analgesic actions and could contribute to depression in reflex excitability of motoneurons."}
{"id": "PMID:217701", "title": "ACTH4--10 antagonism of morphine-induced behavioral activation in the mouse.", "content": "The 4--10 fragment of adrenocorticotrophic hormone (ACTH4--10; Met-Glu-His-Phe-Arg-Trp-Gly) was administered intracerebroventricularly to C57Bl mice with and without concurrent systemic injection of a standard dose of morphine sulfate. Morphine produced stereotyped behavioral activation (running, environmental oblivion, Straub tail) which was antagonized in a dose related fashion by the ACTH fragment. This extends the range of opiate--ACTH4--10 interactions to a novel species and behavioral model, and is consistent with previous findings.", "contents": "ACTH4--10 antagonism of morphine-induced behavioral activation in the mouse. The 4--10 fragment of adrenocorticotrophic hormone (ACTH4--10; Met-Glu-His-Phe-Arg-Trp-Gly) was administered intracerebroventricularly to C57Bl mice with and without concurrent systemic injection of a standard dose of morphine sulfate. Morphine produced stereotyped behavioral activation (running, environmental oblivion, Straub tail) which was antagonized in a dose related fashion by the ACTH fragment. This extends the range of opiate--ACTH4--10 interactions to a novel species and behavioral model, and is consistent with previous findings."}
{"id": "PMID:217702", "title": "Effect of L-glutamate and kainate on rat cerebellar cGMP levels in vivo.", "content": "L-glutamate and kainate administered intracerebroventricularly (i.c.v.) both produced dose-dependent increases in rat cerebellar cGMP. The increased cGMP produced by L-glutamate, but not that produced by kainate, could be completely abolished by the glutamate antagonist glutamate diethylester which had no effect alone. The data suggest that L-glutamate and kainate may be acting upon different sub-populations of glutamate receptors, both of which may be involved in the regulation of cerebellar cGMP levels.", "contents": "Effect of L-glutamate and kainate on rat cerebellar cGMP levels in vivo. L-glutamate and kainate administered intracerebroventricularly (i.c.v.) both produced dose-dependent increases in rat cerebellar cGMP. The increased cGMP produced by L-glutamate, but not that produced by kainate, could be completely abolished by the glutamate antagonist glutamate diethylester which had no effect alone. The data suggest that L-glutamate and kainate may be acting upon different sub-populations of glutamate receptors, both of which may be involved in the regulation of cerebellar cGMP levels."}
{"id": "PMID:217703", "title": "The effect of sleep upon the transmission of afferent activity in the somatic afferent system.", "content": "Macaque monkeys were trained to fall asleep while sitting in a primate chair with their heads restrained. A gentle vibratory stimulus was delivered to the glabrous skin of the hand; it did not provoke awakening or change the sleep cycle of the macaque.  Postcentral neuronal response to the amplitude of a sine wave mechanical stimulus and neuronal spontaneous activity were observed repetitively during all the phases of normal night sleep cycles. One hundred six neurons which could be entrained by  a cutaneous mechanical stimulus were studied during both waking and sleep. At threshold, cyclic entrainment of the discharges of postcentral neurons decreased to 81 +/- 0.25% during light sleep (S1 + S2), to 64 +/- 0.26% during deep sleep (S3 + S4), and to 9 +/- 0.98% during desynchronized sleep with rapid eye movements (REMs).", "contents": "The effect of sleep upon the transmission of afferent activity in the somatic afferent system. Macaque monkeys were trained to fall asleep while sitting in a primate chair with their heads restrained. A gentle vibratory stimulus was delivered to the glabrous skin of the hand; it did not provoke awakening or change the sleep cycle of the macaque.  Postcentral neuronal response to the amplitude of a sine wave mechanical stimulus and neuronal spontaneous activity were observed repetitively during all the phases of normal night sleep cycles. One hundred six neurons which could be entrained by  a cutaneous mechanical stimulus were studied during both waking and sleep. At threshold, cyclic entrainment of the discharges of postcentral neurons decreased to 81 +/- 0.25% during light sleep (S1 + S2), to 64 +/- 0.26% during deep sleep (S3 + S4), and to 9 +/- 0.98% during desynchronized sleep with rapid eye movements (REMs)."}
{"id": "PMID:217704", "title": "Responses to stimulation of marginal fibers in the teleostean optic tectum.", "content": "The marginal fibers (mf) constitute a major fiber component of the teleostean optic tectum, and this report deals with the physiological properties of these fibers and their postsynaptic elements. The mf are unmyelinated axons which originate at the torus longitudinalis and run lateralwards, parallel to one another, along the tectum's most superficial layer (stratum marginale). Here they synapse upon the dendritic arborizations of the pyramidal (p) neurons. These arborizations originate from a single apical dendritic shaft which, near the soma, receives retinofugal axon terminals. The p-neurons also have a basal dendritic shaft and a descending axon, both of which branch out horizontally at the stratum griseum centrale (SGC). The mf were stimulated through surface microelectrodes, and field potentials were recorded on-beam throughout the tectal thickness by means of micropipettes. The mf action potential (M-spike) may show two negative subpeaks which propagate at 0.20 and 0.16 m/s. Its refractory period is followed by a period of increased amplitude and decreased latency. The M-spike is followed by a series of slow waves, namely: (a) The S-wave, which probably represents the monosynaptic depolarization of the p-neuron's apical arbor; (b) The N-wave which possibly represents an active current sink at the point where these dendritic arborizations merge into the apical dendritic shaft; (c) The D-wave, recorded at the SGC, which possibly represents the activation of the p-neuron's axon and terminals (and perhpas also basal dendritic shaft and branches); and (d) the L-wave, which might represent a later depolarization of the p-neuron's apical arborizations. Morphologically and electrophysiologically, there are several similarities between the tectal mf/p-neuron system and the cerebellar parallel fiber/Purkinje cell system.", "contents": "Responses to stimulation of marginal fibers in the teleostean optic tectum. The marginal fibers (mf) constitute a major fiber component of the teleostean optic tectum, and this report deals with the physiological properties of these fibers and their postsynaptic elements. The mf are unmyelinated axons which originate at the torus longitudinalis and run lateralwards, parallel to one another, along the tectum's most superficial layer (stratum marginale). Here they synapse upon the dendritic arborizations of the pyramidal (p) neurons. These arborizations originate from a single apical dendritic shaft which, near the soma, receives retinofugal axon terminals. The p-neurons also have a basal dendritic shaft and a descending axon, both of which branch out horizontally at the stratum griseum centrale (SGC). The mf were stimulated through surface microelectrodes, and field potentials were recorded on-beam throughout the tectal thickness by means of micropipettes. The mf action potential (M-spike) may show two negative subpeaks which propagate at 0.20 and 0.16 m/s. Its refractory period is followed by a period of increased amplitude and decreased latency. The M-spike is followed by a series of slow waves, namely: (a) The S-wave, which probably represents the monosynaptic depolarization of the p-neuron's apical arbor; (b) The N-wave which possibly represents an active current sink at the point where these dendritic arborizations merge into the apical dendritic shaft; (c) The D-wave, recorded at the SGC, which possibly represents the activation of the p-neuron's axon and terminals (and perhpas also basal dendritic shaft and branches); and (d) the L-wave, which might represent a later depolarization of the p-neuron's apical arborizations. Morphologically and electrophysiologically, there are several similarities between the tectal mf/p-neuron system and the cerebellar parallel fiber/Purkinje cell system."}
{"id": "PMID:217706", "title": "Glutamate and aspartate mimic the afferent transmitter in the cochlea.", "content": "Glutamate (50 mM) and aspartate (50 mM) applied intracochlearly increase the spontaneous activity of ganglion cells of the auditory nerve. This activity may account for the decreased magnitude of the compound action potential observed with these substances in previous studies, and also may be additional evidence that these substances have a role in synaptic transmission between the hair cells and primary auditory afferent nerve cells.", "contents": "Glutamate and aspartate mimic the afferent transmitter in the cochlea. Glutamate (50 mM) and aspartate (50 mM) applied intracochlearly increase the spontaneous activity of ganglion cells of the auditory nerve. This activity may account for the decreased magnitude of the compound action potential observed with these substances in previous studies, and also may be additional evidence that these substances have a role in synaptic transmission between the hair cells and primary auditory afferent nerve cells."}
{"id": "PMID:217707", "title": "Monocular deprivation and the signal transmission by X- and Y-neurons of the cat lateral geniculate nucleus.", "content": "1. In adult cats deprived monocularly from the second week of life, single neurons were recorded from the optic tract (OT), the lateral geniculate body (pars dorsalis, LGN) and the optic radiation (OR). The neurons were classified according to their visual response properties (Y/X) or their latencies to OT electrical stimulation (class I/II). 2. A close positive correlation (greater than 95%) was found between the visual classification and the latency classification (Y = I, X =  II). 3. The relative frequency of class I/Y-neurons was reduced in the group of pattern-deprived LGN neurons, but normal in the pattern-deprived OR neurons. 4. The ratio of the r1 and r2 wave amplitude of the OR-evoked potentials elicited by electrical stimulation of the normal or the deprived eye optic nerve was not affected by pattern deprivation. 5. The activity pattern of neurons recorded from the LGN or the OR did not differ in normal and pattern-deprived neurons belonging to the same class (on-center/off-center; Y/X). The same was true for the neuronal responses to electrical stimulation of the OT at different stimulus frequencies (1-200 stimuli/s). 6. The average maintained activity of pattern-deprived OT or OR neurons recorded while the eyelids of the deprived eye were still closed was either equal to or even somewhat higher than the average activity of the corresponding normal neurons. This was true when the patterned stimuli were presented stationary or were moved at random within the visual field simulating the effect of eye and head movements. The pattern deprivation effects found morphologically and physiologically in the visual cortex are, therefore, not induced by a diminished average activity of the input neurons from the deprived eye.", "contents": "Monocular deprivation and the signal transmission by X- and Y-neurons of the cat lateral geniculate nucleus. 1. In adult cats deprived monocularly from the second week of life, single neurons were recorded from the optic tract (OT), the lateral geniculate body (pars dorsalis, LGN) and the optic radiation (OR). The neurons were classified according to their visual response properties (Y/X) or their latencies to OT electrical stimulation (class I/II). 2. A close positive correlation (greater than 95%) was found between the visual classification and the latency classification (Y = I, X =  II). 3. The relative frequency of class I/Y-neurons was reduced in the group of pattern-deprived LGN neurons, but normal in the pattern-deprived OR neurons. 4. The ratio of the r1 and r2 wave amplitude of the OR-evoked potentials elicited by electrical stimulation of the normal or the deprived eye optic nerve was not affected by pattern deprivation. 5. The activity pattern of neurons recorded from the LGN or the OR did not differ in normal and pattern-deprived neurons belonging to the same class (on-center/off-center; Y/X). The same was true for the neuronal responses to electrical stimulation of the OT at different stimulus frequencies (1-200 stimuli/s). 6. The average maintained activity of pattern-deprived OT or OR neurons recorded while the eyelids of the deprived eye were still closed was either equal to or even somewhat higher than the average activity of the corresponding normal neurons. This was true when the patterned stimuli were presented stationary or were moved at random within the visual field simulating the effect of eye and head movements. The pattern deprivation effects found morphologically and physiologically in the visual cortex are, therefore, not induced by a diminished average activity of the input neurons from the deprived eye."}
{"id": "PMID:217708", "title": "Locally evoked potentials in slices of rat neostriatum: a tool for the investigation of intrinsic excitatory processes.", "content": "Field potentials, extracellular unitary discharges and intracellular potentials evoked by intrastriatal stimulation were recorded from slices (thickness 200-400 micron) of rat neostriatum maintained in an artificial medium. The field potentials consisted of two negative waves appearing at latencies of 0.5-1.5 ms (N-1) and 2-4 ms (N-2). Extracellular unitary records showed two typed of discharges, one with short but constant latencies at threshold level stimulation and the other with longer and variable latencies. In intracellular recordings the late discharge was seen to arise from EPSPs. Based on the intra- and extracellular unitary records, N-1 was identified as the population spike of antidromically or directly activated unitary discharges and N-2 as that of orthodromically activated discharges. This interpretation was substantiated by the fact that the N-2 potential was blocked in a perfusion medium containing a lower Ca++ or a higher Mg++ concentration than the standard solution. Neither interruption of ascending neostriatal inputs nor decortication 14 days prior to recording altered the configuration of the locally evoked potentials or the probability of synaptically driven discharge occurrence. Thus by intrastriatal stimulation, neostriatal neurons are activated antidromically or directly and/or orthodromically through intrinsic excitatroy synapses. Since the intracellular recordings showed that neostriatal neurons can be well preserved, this preparation can be regarded as a useful tool for electrophysiological and neuropharmacological investigations on intrinsic excitatory processes in the neostriatum.", "contents": "Locally evoked potentials in slices of rat neostriatum: a tool for the investigation of intrinsic excitatory processes. Field potentials, extracellular unitary discharges and intracellular potentials evoked by intrastriatal stimulation were recorded from slices (thickness 200-400 micron) of rat neostriatum maintained in an artificial medium. The field potentials consisted of two negative waves appearing at latencies of 0.5-1.5 ms (N-1) and 2-4 ms (N-2). Extracellular unitary records showed two typed of discharges, one with short but constant latencies at threshold level stimulation and the other with longer and variable latencies. In intracellular recordings the late discharge was seen to arise from EPSPs. Based on the intra- and extracellular unitary records, N-1 was identified as the population spike of antidromically or directly activated unitary discharges and N-2 as that of orthodromically activated discharges. This interpretation was substantiated by the fact that the N-2 potential was blocked in a perfusion medium containing a lower Ca++ or a higher Mg++ concentration than the standard solution. Neither interruption of ascending neostriatal inputs nor decortication 14 days prior to recording altered the configuration of the locally evoked potentials or the probability of synaptically driven discharge occurrence. Thus by intrastriatal stimulation, neostriatal neurons are activated antidromically or directly and/or orthodromically through intrinsic excitatroy synapses. Since the intracellular recordings showed that neostriatal neurons can be well preserved, this preparation can be regarded as a useful tool for electrophysiological and neuropharmacological investigations on intrinsic excitatory processes in the neostriatum."}
{"id": "PMID:217710", "title": "Ultrastructural organization of thrombocytes in normal monkeys (Macaca arctoides) and in those with experimental viral malignant lymphoma.", "content": "Data on platelet ultrastructure of 6 M. arctoides monkeys investigated before and during experimental viral malignant lymphoma are presented. It has been established that the inner structure of thrombocytes in healthy monkeys was almost similar to that of man. In experimental malignant lymphoma, irrespective of the clinical period of the disease, a decrease of alpha-, beta- and sigma-granules, a decrease of the functional activity of thrombocytes and an increase of delta-granules and glycogen granulation content were observed. The above mentioned disturbances can be a result of changes of megakaryocytes in malignant lymphoma. No viral particles in thrombocytes of neither healthy nor sick monkeys have been revealed.", "contents": "Ultrastructural organization of thrombocytes in normal monkeys (Macaca arctoides) and in those with experimental viral malignant lymphoma. Data on platelet ultrastructure of 6 M. arctoides monkeys investigated before and during experimental viral malignant lymphoma are presented. It has been established that the inner structure of thrombocytes in healthy monkeys was almost similar to that of man. In experimental malignant lymphoma, irrespective of the clinical period of the disease, a decrease of alpha-, beta- and sigma-granules, a decrease of the functional activity of thrombocytes and an increase of delta-granules and glycogen granulation content were observed. The above mentioned disturbances can be a result of changes of megakaryocytes in malignant lymphoma. No viral particles in thrombocytes of neither healthy nor sick monkeys have been revealed."}
{"id": "PMID:217711", "title": "Effect of various solubilizers on angiotensinII receptors in bovine adrenocortical plasma membranes.", "content": "3 nonionic detergents, Triton X-100, Lubrol WX and NP-40, inhibited binding of [3H]-ATII to bovine adrenocortical plasma membranes. This effect appeared to be direct and not due to solubilization of the ATII receptor by these agents. Sodium deoxycholate and the chaotropic ions, ClO4- and Br-, produced effects similar to the nonionic detergents.", "contents": "Effect of various solubilizers on angiotensinII receptors in bovine adrenocortical plasma membranes. 3 nonionic detergents, Triton X-100, Lubrol WX and NP-40, inhibited binding of [3H]-ATII to bovine adrenocortical plasma membranes. This effect appeared to be direct and not due to solubilization of the ATII receptor by these agents. Sodium deoxycholate and the chaotropic ions, ClO4- and Br-, produced effects similar to the nonionic detergents."}
{"id": "PMID:217712", "title": "Influence of alpha-MSH and ACTH on cortical bone remodelling in hypophysectomized rats.", "content": "Hypophysectomy increases both periosteal resorption and endosteal apposition along the femur diaphysis in rat. Administration of alpha-MSH decreased the periosteal resorption but had no effect on the endosteal apposition. ACTH had only minor effects on the endosteum. Thus, alpha-MSH and ACTH, in the doses used, have different effects on cortical bone in rat. The effect of alpha-MSH on cortical bone could be an effect of the hormone alone or by its stimulation of other factors.", "contents": "Influence of alpha-MSH and ACTH on cortical bone remodelling in hypophysectomized rats. Hypophysectomy increases both periosteal resorption and endosteal apposition along the femur diaphysis in rat. Administration of alpha-MSH decreased the periosteal resorption but had no effect on the endosteal apposition. ACTH had only minor effects on the endosteum. Thus, alpha-MSH and ACTH, in the doses used, have different effects on cortical bone in rat. The effect of alpha-MSH on cortical bone could be an effect of the hormone alone or by its stimulation of other factors."}
{"id": "PMID:217713", "title": "[Adenylate cyclase activation and its effects on intracellular cAMP in infected KB cells during trypsin-induced infectious Senda\u00ef virus production (author's transl)].", "content": "KB cells infected by Senda\u00ef virus can produce infectious virus if they are trypsinated twice over 24 h. Adenylate cyclase activity in infected KB cells is higher and more strongly activated by trypsin than that of control cells, but intracellular concentration of cAMP is the same, except during a short time after trypsinations, especially after the second trypsination which causes infectious virus production. During this short time, intracellular cAMP is slightly higher in infected cells. This miseffect of adenylate cyclase activation on intracellular cAMP concentrations might be related to an increased cell permeability caused by trypsin.", "contents": "[Adenylate cyclase activation and its effects on intracellular cAMP in infected KB cells during trypsin-induced infectious Senda\u00ef virus production (author's transl)]. KB cells infected by Senda\u00ef virus can produce infectious virus if they are trypsinated twice over 24 h. Adenylate cyclase activity in infected KB cells is higher and more strongly activated by trypsin than that of control cells, but intracellular concentration of cAMP is the same, except during a short time after trypsinations, especially after the second trypsination which causes infectious virus production. During this short time, intracellular cAMP is slightly higher in infected cells. This miseffect of adenylate cyclase activation on intracellular cAMP concentrations might be related to an increased cell permeability caused by trypsin."}
{"id": "PMID:217714", "title": "The effect of bisamidines of 2,6-diaminoanthraquinone on Entamoeba histolytica infections in rats and hamsters.", "content": "Bisamidines of 2,6-diaminoanthraquinone have demonstrated potent activity against cecal and hepatic Entamoeba histolytica infections in rats and hamsters, respectively. A number of these compounds compared favorably, in overall drug efficacy, with metronidazole and other standard agents.", "contents": "The effect of bisamidines of 2,6-diaminoanthraquinone on Entamoeba histolytica infections in rats and hamsters. Bisamidines of 2,6-diaminoanthraquinone have demonstrated potent activity against cecal and hepatic Entamoeba histolytica infections in rats and hamsters, respectively. A number of these compounds compared favorably, in overall drug efficacy, with metronidazole and other standard agents."}
{"id": "PMID:217715", "title": "The anticonvulsant effects of propranolol and beta-adrenergic blockade.", "content": "The anticonvulsant activity of racemic and (+)-propranolol was studied in rats. Neither drug changed the current to produce a minimal seizure in 50% of animals. Both drugs were effective in the maximal electroshock seizure test, the (+) isomer being more potent than the racemic form. Since the (+) isomer is practically devoid of beta-adrenergic blocking activity, the anticonvulsant effects of propranolol do not result from beta-adrenergic blockade.", "contents": "The anticonvulsant effects of propranolol and beta-adrenergic blockade. The anticonvulsant activity of racemic and (+)-propranolol was studied in rats. Neither drug changed the current to produce a minimal seizure in 50% of animals. Both drugs were effective in the maximal electroshock seizure test, the (+) isomer being more potent than the racemic form. Since the (+) isomer is practically devoid of beta-adrenergic blocking activity, the anticonvulsant effects of propranolol do not result from beta-adrenergic blockade."}
{"id": "PMID:217716", "title": "Effects of [N-(2-oxo-3,5,7-cycloheptatrien-1-yl)] aminooxoacetic acid ethyl ester (AY-25,674) on cyclic 3',5'-nucleotide formation and phosphodiesterase activity.", "content": "The orally-effective antiallergic compound [N-(2-oxo-3,5,7-cycloheptatrien-1-yl)] aminooxoacetic acid ethyl ester (AY-25,674) exhibited a potency equivalent to or 3 times less than theophylline in inhibiting guinea-pig lung and beef heart PDE, respectively, AY-25,674 did not affect the basal activity of guinea-pig lung adenyl cyclase. Although part of the antiallergic activity of AY-25,674 may be due to the ability to elevate cyclic AMP levels by PDE inhibition, other modes of action appear to be of greater relevance.", "contents": "Effects of [N-(2-oxo-3,5,7-cycloheptatrien-1-yl)] aminooxoacetic acid ethyl ester (AY-25,674) on cyclic 3',5'-nucleotide formation and phosphodiesterase activity. The orally-effective antiallergic compound [N-(2-oxo-3,5,7-cycloheptatrien-1-yl)] aminooxoacetic acid ethyl ester (AY-25,674) exhibited a potency equivalent to or 3 times less than theophylline in inhibiting guinea-pig lung and beef heart PDE, respectively, AY-25,674 did not affect the basal activity of guinea-pig lung adenyl cyclase. Although part of the antiallergic activity of AY-25,674 may be due to the ability to elevate cyclic AMP levels by PDE inhibition, other modes of action appear to be of greater relevance."}
{"id": "PMID:217717", "title": "Effects of lithium chloride on peripheral acetylcholine release and brain acetylcholine levels in the guinea-pig.", "content": "Lithium chloride administered acutely or chronically to guinea-pigs had no effect on brain level of acetylcholine or on peripheral release of acetylcholine from longitudinal muscle of the ileum. The results suggest differences between in vitro and in vivo action of lithium.", "contents": "Effects of lithium chloride on peripheral acetylcholine release and brain acetylcholine levels in the guinea-pig. Lithium chloride administered acutely or chronically to guinea-pigs had no effect on brain level of acetylcholine or on peripheral release of acetylcholine from longitudinal muscle of the ileum. The results suggest differences between in vitro and in vivo action of lithium."}
{"id": "PMID:217718", "title": "Ontogenetic changes in relative levels of cyclic AMP-dependent and cyclic GMP-dependent protein kinases in prostates, epididymides and testes from guinea-pigs.", "content": "Changes in relative levels of cyclic AMP-dependent protein kinase (A-PK) and cyclic GMP-dependent protein kinase (G-PK) in prostates, epidymides and testes from guinea-pigs were examined at 3 different ages. During postnatal development, a decrease in the ratio of the 2 classes of protein kinases was seen in prostates, whereas increases of the ratios of the enzymes were found in epididymides and testes.", "contents": "Ontogenetic changes in relative levels of cyclic AMP-dependent and cyclic GMP-dependent protein kinases in prostates, epididymides and testes from guinea-pigs. Changes in relative levels of cyclic AMP-dependent protein kinase (A-PK) and cyclic GMP-dependent protein kinase (G-PK) in prostates, epidymides and testes from guinea-pigs were examined at 3 different ages. During postnatal development, a decrease in the ratio of the 2 classes of protein kinases was seen in prostates, whereas increases of the ratios of the enzymes were found in epididymides and testes."}
{"id": "PMID:217719", "title": "Prostaglandin-like substances in Propionibacterium acnes II. Stimulatory effect on ovarian cyclic AMP.", "content": "The prostaglandin-like substances (PLS) from Propionibacterium acnes increased the ovarian tissue levels of cyclic AMP (cAMP) approximately 2-fold. The lipid material extracted from P. acnes thus behaved like PG's of the E-type, and since it is unlikely that other known stimulators of the ovarian cAMP system can be present in the bacterial lipid fraction, these experiments give further evidence in favour of the occurrence of PLS in P. acnes.", "contents": "Prostaglandin-like substances in Propionibacterium acnes II. Stimulatory effect on ovarian cyclic AMP. The prostaglandin-like substances (PLS) from Propionibacterium acnes increased the ovarian tissue levels of cyclic AMP (cAMP) approximately 2-fold. The lipid material extracted from P. acnes thus behaved like PG's of the E-type, and since it is unlikely that other known stimulators of the ovarian cAMP system can be present in the bacterial lipid fraction, these experiments give further evidence in favour of the occurrence of PLS in P. acnes."}
{"id": "PMID:217720", "title": "Decreased cyclic GMP levels in rat cecum mucosa during adaptive stimulation of Na-K-ATPase.", "content": "In rat cecal mucosa, Na-K-ATPase specific activity and sodium and fluid absorption were increased by giving polyethylene glycol administration with the drinking water. Whereas cyclic AMP levels were unchanged, cyclic GMP was reduced by about 50%. This finding suggests a regulatory role of cyclic GMP in intestinal sodium and fluid absorption.", "contents": "Decreased cyclic GMP levels in rat cecum mucosa during adaptive stimulation of Na-K-ATPase. In rat cecal mucosa, Na-K-ATPase specific activity and sodium and fluid absorption were increased by giving polyethylene glycol administration with the drinking water. Whereas cyclic AMP levels were unchanged, cyclic GMP was reduced by about 50%. This finding suggests a regulatory role of cyclic GMP in intestinal sodium and fluid absorption."}
{"id": "PMID:217721", "title": "Zinc deficiency and lung converting enzyme activity in rats.", "content": "Angiotensin converting enzyme activity was found to be significantly decreased in the isolated perfused lung from zinc-deficient rats when compared with that of controls. Addition of zinc ion to the superfusion medium did not cause a recovery in this decreased activity of the enzyme. It is postulated that zinc deficiency probably produces a structural change in the lung angiotensin converting enzyme.", "contents": "Zinc deficiency and lung converting enzyme activity in rats. Angiotensin converting enzyme activity was found to be significantly decreased in the isolated perfused lung from zinc-deficient rats when compared with that of controls. Addition of zinc ion to the superfusion medium did not cause a recovery in this decreased activity of the enzyme. It is postulated that zinc deficiency probably produces a structural change in the lung angiotensin converting enzyme."}
{"id": "PMID:217722", "title": "Anticonvulsant activity of farnesylacetone epoxide--a novel marine natural product.", "content": "A marine natural product, farnesylacetone epoxide, which is chemically related to juvenile hormone, has anticonvulsant properties at nonsedative doses in mice.", "contents": "Anticonvulsant activity of farnesylacetone epoxide--a novel marine natural product. A marine natural product, farnesylacetone epoxide, which is chemically related to juvenile hormone, has anticonvulsant properties at nonsedative doses in mice."}
{"id": "PMID:217723", "title": "Reappearance of HCG-receptors in immature rat ovary after HCG-treatment is not due to receptor synthesis.", "content": "In 24-day-old rats the reappearance of ovarian HCG-receptors after the injection of 200 IU HCG in independent of protein synthesis. The reutilization of occupied receptors in immature female rats is due to dissociation of the receptor-hormone complex.", "contents": "Reappearance of HCG-receptors in immature rat ovary after HCG-treatment is not due to receptor synthesis. In 24-day-old rats the reappearance of ovarian HCG-receptors after the injection of 200 IU HCG in independent of protein synthesis. The reutilization of occupied receptors in immature female rats is due to dissociation of the receptor-hormone complex."}
{"id": "PMID:217729", "title": "[Substances having antiviral activity. IX. Synthesis and antiviral activity of 1-acyl-2-halo-3-formylindole thiosemicarbazones].", "content": "Some thiosemicarbazones of 1-acyl-2-chloro-3-formylindoles were synthesized and investigated for antiviral activity against vaccinia virus, HID stock and parainfluenza virus type 3 HA-I/CR-8 stock. Evidence of antiviral activity was found only against vaccinia virus, and was particular significant with the m-substituted 1-benzoyl-2-chloro-3-formylindoles. The first results of 2-substitution of chlorine by bromine in the indole skeleton, are reported.", "contents": "[Substances having antiviral activity. IX. Synthesis and antiviral activity of 1-acyl-2-halo-3-formylindole thiosemicarbazones]. Some thiosemicarbazones of 1-acyl-2-chloro-3-formylindoles were synthesized and investigated for antiviral activity against vaccinia virus, HID stock and parainfluenza virus type 3 HA-I/CR-8 stock. Evidence of antiviral activity was found only against vaccinia virus, and was particular significant with the m-substituted 1-benzoyl-2-chloro-3-formylindoles. The first results of 2-substitution of chlorine by bromine in the indole skeleton, are reported."}
{"id": "PMID:217728", "title": "[Comparative effect of psychotropic agents on orienting-motor responses and cerebral Na,K-ATPase activity in vivo].", "content": "Levomepromazine, chlorpromazine (10 and 30 mg/kg), etaperaxine, haloperidol (3 and 10 mg/kg) inhibited the exploratory-motor reactions of rats and the brain Na, K-ATPase activity an hour after their administration. The effects of tranquilizers as well as of antidepressants on the exploratory reactions and on the enzyme activity were not found to stand in a clearcut relation to each other. The stimulating effect of amphethamine (3 mg/kg) was accompanied by activation and suppressive action (10 mg/kg)--by inhibition of the enzyme. It is suggested that the inhibition of the brain Na, K-ATPase activity by psychotropic drugs may play a role in the mechanism of their sedative action.", "contents": "[Comparative effect of psychotropic agents on orienting-motor responses and cerebral Na,K-ATPase activity in vivo]. Levomepromazine, chlorpromazine (10 and 30 mg/kg), etaperaxine, haloperidol (3 and 10 mg/kg) inhibited the exploratory-motor reactions of rats and the brain Na, K-ATPase activity an hour after their administration. The effects of tranquilizers as well as of antidepressants on the exploratory reactions and on the enzyme activity were not found to stand in a clearcut relation to each other. The stimulating effect of amphethamine (3 mg/kg) was accompanied by activation and suppressive action (10 mg/kg)--by inhibition of the enzyme. It is suggested that the inhibition of the brain Na, K-ATPase activity by psychotropic drugs may play a role in the mechanism of their sedative action."}
{"id": "PMID:217789", "title": "A study of premarin intravenous and its influence on blood loss during transurethral prostatectomy.", "content": "In a double-blind comparative study conjugated equine oestrogens (USP) (Premarin Intravenous) and saline were administered intravenously to patients undergoing transurethral prostatectomy. This paper proves that the placebo group (saline) displays a tendency, as indicated by two statistical tests, towards a significant increase in the red blood cells lost in the 24-hours after the operation. The Premarin Intravenous group showed no such tendency.", "contents": "A study of premarin intravenous and its influence on blood loss during transurethral prostatectomy. In a double-blind comparative study conjugated equine oestrogens (USP) (Premarin Intravenous) and saline were administered intravenously to patients undergoing transurethral prostatectomy. This paper proves that the placebo group (saline) displays a tendency, as indicated by two statistical tests, towards a significant increase in the red blood cells lost in the 24-hours after the operation. The Premarin Intravenous group showed no such tendency."}
{"id": "PMID:217790", "title": "Autoantibodies to islet cells in diabetes mellitus.", "content": "Numerous reports have confirmed the presence of islet cell antibodies in diabetic patients. These are found mostly in newly diagnosed insulin-dependent diabetic patients and in patients who have autoimmune polyendocrine disorders. Antibodies to beta cells, somatostatin, and glucagon-producing cells have been described as well. All these antibodies give strictly intracytoplasmic staining. It is therefore difficult to understand their role in the pathogenesis of pancreatic damage. The presence of another antibody is thus postulated.", "contents": "Autoantibodies to islet cells in diabetes mellitus. Numerous reports have confirmed the presence of islet cell antibodies in diabetic patients. These are found mostly in newly diagnosed insulin-dependent diabetic patients and in patients who have autoimmune polyendocrine disorders. Antibodies to beta cells, somatostatin, and glucagon-producing cells have been described as well. All these antibodies give strictly intracytoplasmic staining. It is therefore difficult to understand their role in the pathogenesis of pancreatic damage. The presence of another antibody is thus postulated."}
{"id": "PMID:217791", "title": "Insulin secretion and cyclic adenosine 3', 5'-monophosphate levels in pancreatic islets of fed and fasted rats. Time course and dose kinetics during glucose stimulation.", "content": "Incubation of pancreatic islets of fed rats at glucose 10 and 15 mM induced a rapid rise of the islet cyclic adenosine 3',5'-monophosphate (cAMP) content. Maximum levels were attained at 15 min and lasted until 30 min, after which cAMP declined again. Insulin secretion increased most rapidly from 15 min onward, i.e. after the rapid rise of cAMP. Islet cAMP at either 15 or 30 min showed its major concentration-dependent increase between glucose 7.5 and 10 mM. Glucose 15 mM did not further enhance the cAMP response, although this concentration increased insulin secretion more than two-fold over values observed at glucose 10 mM. Thus, the glucose dose-response relations for cAMP levels and insulin secretion appear to be different, indicating that factors other than cAMP alone determine the secretory response to glucose. Fasting for 24 and 72 h progressively inhibited glucose-induced insulin secretion. At glucose 15 mM the secretory inhibition disappeared after 30-45 min, but at glucose 10 mM it persisted for at least 90 min. Increasing periods of fasting also progressively delayed and inhibited the cAMP response to glucose, most strongly at glucose 10 mM. Fasting for 24 h shifted the glucose dose-response curves for cAMP and insulin secretion to the right, but the maximum responses at glucose 37.5 mM were not significantly inhibited. The secretory inhibition appeared to be linearly related with the cAMP content in two different ways: (a) At fixed concentrations of glucose, the increasing of the cAMP response (at 15 min) as induced by 24 and 72 h of fasting correlated with the secretory inhibition over the initial 30 min. (b) At one fixed period of fasting (24 h), the variable percent inhibition of the cAMP response to graded concentrations of glucose (5-37.5 mM) correlated with the percent secretory inhibition at these concentrations. These correlations were no longer apparent after 30 min of incubation. The results support the view that inhibition of the adenylate cyclase-cAMP system is a major determinant factor in fasting-induced impairment of insulin secretion during the initial 30 min of glucose stimulation.", "contents": "Insulin secretion and cyclic adenosine 3', 5'-monophosphate levels in pancreatic islets of fed and fasted rats. Time course and dose kinetics during glucose stimulation. Incubation of pancreatic islets of fed rats at glucose 10 and 15 mM induced a rapid rise of the islet cyclic adenosine 3',5'-monophosphate (cAMP) content. Maximum levels were attained at 15 min and lasted until 30 min, after which cAMP declined again. Insulin secretion increased most rapidly from 15 min onward, i.e. after the rapid rise of cAMP. Islet cAMP at either 15 or 30 min showed its major concentration-dependent increase between glucose 7.5 and 10 mM. Glucose 15 mM did not further enhance the cAMP response, although this concentration increased insulin secretion more than two-fold over values observed at glucose 10 mM. Thus, the glucose dose-response relations for cAMP levels and insulin secretion appear to be different, indicating that factors other than cAMP alone determine the secretory response to glucose. Fasting for 24 and 72 h progressively inhibited glucose-induced insulin secretion. At glucose 15 mM the secretory inhibition disappeared after 30-45 min, but at glucose 10 mM it persisted for at least 90 min. Increasing periods of fasting also progressively delayed and inhibited the cAMP response to glucose, most strongly at glucose 10 mM. Fasting for 24 h shifted the glucose dose-response curves for cAMP and insulin secretion to the right, but the maximum responses at glucose 37.5 mM were not significantly inhibited. The secretory inhibition appeared to be linearly related with the cAMP content in two different ways: (a) At fixed concentrations of glucose, the increasing of the cAMP response (at 15 min) as induced by 24 and 72 h of fasting correlated with the secretory inhibition over the initial 30 min. (b) At one fixed period of fasting (24 h), the variable percent inhibition of the cAMP response to graded concentrations of glucose (5-37.5 mM) correlated with the percent secretory inhibition at these concentrations. These correlations were no longer apparent after 30 min of incubation. The results support the view that inhibition of the adenylate cyclase-cAMP system is a major determinant factor in fasting-induced impairment of insulin secretion during the initial 30 min of glucose stimulation."}
{"id": "PMID:217792", "title": "Mononeuropathy in diabetes mellitus.", "content": "Fifty-one diabetic patients with mononeuropathies wereoneuropathy were studied to examine possible etiological factors, to determine the relationship with other diabetic complications, and to correlate with the presence and severity of background peripheral and autonomic neuropathy. The median, ulnar, and lateral popliteal nerves were most commonly affected and cranial neuropathy was relatively uncommon. When bilateral involvement of the same nerve was excluded, multiple mononeuropathies were found in only five patients. Median and ulnar mononeuropathy were gradual in onset and affected the dominant limb whereas other types of mononeuropathies were acute in onset with no predilection for either side. No consistent relationship was shown between the onset of mononeuropathy and age, sex, diabetic treatment, duration of diabetes, diabetic control, or other diabetic complications. In particular, there was no significant background peripheral and autonomic neuropathy, as assessed clinically and by objective tests, in almost one-half of the patients studied. It is concluded that diabetic mononeuropathy may occur independently of peripheral and autonomic neuropathy. It is possible, however, that a minimal degree of background damage, known to be present in all diabetic patients, may render them more susceptible than the general population to the various factors causing mononeuropathy.", "contents": "Mononeuropathy in diabetes mellitus. Fifty-one diabetic patients with mononeuropathies wereoneuropathy were studied to examine possible etiological factors, to determine the relationship with other diabetic complications, and to correlate with the presence and severity of background peripheral and autonomic neuropathy. The median, ulnar, and lateral popliteal nerves were most commonly affected and cranial neuropathy was relatively uncommon. When bilateral involvement of the same nerve was excluded, multiple mononeuropathies were found in only five patients. Median and ulnar mononeuropathy were gradual in onset and affected the dominant limb whereas other types of mononeuropathies were acute in onset with no predilection for either side. No consistent relationship was shown between the onset of mononeuropathy and age, sex, diabetic treatment, duration of diabetes, diabetic control, or other diabetic complications. In particular, there was no significant background peripheral and autonomic neuropathy, as assessed clinically and by objective tests, in almost one-half of the patients studied. It is concluded that diabetic mononeuropathy may occur independently of peripheral and autonomic neuropathy. It is possible, however, that a minimal degree of background damage, known to be present in all diabetic patients, may render them more susceptible than the general population to the various factors causing mononeuropathy."}
{"id": "PMID:217796", "title": "An enzymecytochemical study on the adrenal of the freshwater teleost, Clarias batrachus (L.).", "content": "The adrenal homologue of C. batrachus is distributed around the postcardinal vein in the pronephric head kidney. The cortical cells are round or oval in shape. They showed positive reaction for total lipid, glycogen and ascorbic acid. Their intense delta5-3beta HSDH activity indicates their capacity for steroid biosynthesis. In addition, the cortical cells of C. batrachus exhibited strong G-6-PD, NADPH diaphorase, NADH diaphorase, MAO and weak SDH and LDH activity. The presence of MAO suggests the aminergic control of the adrenal in this species and the silver positive fibres seen the cortical cells were hypertrophied, degranulated and the lipid content was also decreased. The chromaffin or medullary cells were distributed in groups among the cortical cells. They are largely oval or angular in shape. They react positively to ferric ferricyanide, chromaffin and argentaffin reactions and ascorbic acid test.", "contents": "An enzymecytochemical study on the adrenal of the freshwater teleost, Clarias batrachus (L.). The adrenal homologue of C. batrachus is distributed around the postcardinal vein in the pronephric head kidney. The cortical cells are round or oval in shape. They showed positive reaction for total lipid, glycogen and ascorbic acid. Their intense delta5-3beta HSDH activity indicates their capacity for steroid biosynthesis. In addition, the cortical cells of C. batrachus exhibited strong G-6-PD, NADPH diaphorase, NADH diaphorase, MAO and weak SDH and LDH activity. The presence of MAO suggests the aminergic control of the adrenal in this species and the silver positive fibres seen the cortical cells were hypertrophied, degranulated and the lipid content was also decreased. The chromaffin or medullary cells were distributed in groups among the cortical cells. They are largely oval or angular in shape. They react positively to ferric ferricyanide, chromaffin and argentaffin reactions and ascorbic acid test."}
{"id": "PMID:217797", "title": "[Follow-up and management of patients with incomplete cone biopsies for dysplasias (author's transl)].", "content": "Report of 86 cone biopsies for dysplasias of the cervix. In 11 of these cases the cone biopsy did not show a clearly dysplasia free margin. These patients were followed from 1 to 6 years without further treatment and none showed a suspicious or positive pap smear. In young patients who desire further pregnancies it appears to be justified to follow without further treatment even after incomplete cone biopsies for dysplasia. Two patients with complete removal of the dysplasia and a normal margin in the cone biopsy later showed positive pap smears. The importance of further follow-up of the cases is stressed.", "contents": "[Follow-up and management of patients with incomplete cone biopsies for dysplasias (author's transl)]. Report of 86 cone biopsies for dysplasias of the cervix. In 11 of these cases the cone biopsy did not show a clearly dysplasia free margin. These patients were followed from 1 to 6 years without further treatment and none showed a suspicious or positive pap smear. In young patients who desire further pregnancies it appears to be justified to follow without further treatment even after incomplete cone biopsies for dysplasia. Two patients with complete removal of the dysplasia and a normal margin in the cone biopsy later showed positive pap smears. The importance of further follow-up of the cases is stressed."}
{"id": "PMID:217798", "title": "[Report on the clinical findings, the treatment, and the course of a case of hemangiofibroma of the adnexa (author's transl)].", "content": "The case of a hemangiofibroma of the right adnexa with locally infiltrative growth is described. The complete operative removal was not possible. A local recurrence was stopped from progressing by ligation of the most important arteries feeding the tumor. Progressive growth was stopped for two years and the patient wihch was an invalid became ambulatory following the operation.", "contents": "[Report on the clinical findings, the treatment, and the course of a case of hemangiofibroma of the adnexa (author's transl)]. The case of a hemangiofibroma of the right adnexa with locally infiltrative growth is described. The complete operative removal was not possible. A local recurrence was stopped from progressing by ligation of the most important arteries feeding the tumor. Progressive growth was stopped for two years and the patient wihch was an invalid became ambulatory following the operation."}
{"id": "PMID:217801", "title": "[Modelling of a modification of chemical mutagenesis in human cells. II. The dependence of the effect on the time of culture treatment].", "content": "The influence of 2,3-aminopropylaminoethylthiophosphoric acid (2,3-APAETP) on the effect of the alkylating agent, thio TEPA, is investigated at different times of cultivation of human peripheral lymphocyte culture. The analysis of correlation equations shows that the results are described by the polynomes of 4-degree in variants treated with thioTEPA and 2,3-APAETP. The protector effect of 2,3-APAETP is determined not by the time from the culture stimulation but the time between the moment of culture treatment with 2,3-APAETP and thioTEPA and the moment of the fixation. It is shown that the points of maximal sensitivity of the cell cycle to thioTEPA and to the protective effect of 2,3-APAETP are similar.", "contents": "[Modelling of a modification of chemical mutagenesis in human cells. II. The dependence of the effect on the time of culture treatment]. The influence of 2,3-aminopropylaminoethylthiophosphoric acid (2,3-APAETP) on the effect of the alkylating agent, thio TEPA, is investigated at different times of cultivation of human peripheral lymphocyte culture. The analysis of correlation equations shows that the results are described by the polynomes of 4-degree in variants treated with thioTEPA and 2,3-APAETP. The protector effect of 2,3-APAETP is determined not by the time from the culture stimulation but the time between the moment of culture treatment with 2,3-APAETP and thioTEPA and the moment of the fixation. It is shown that the points of maximal sensitivity of the cell cycle to thioTEPA and to the protective effect of 2,3-APAETP are similar."}
{"id": "PMID:217802", "title": "Transformation of normal diploid cells by isolated metaphase chromosomes of virus-transformed or spontaneous tumor cells.", "content": "Normal diploid human cells with a limited life-span in culture, as well as primary or secondary cell cultures of mouse or rat embryos, can be transformed in vitro (i.e. grow in soft-agar or low-serum medium) after a single exposure to metaphase chromosomes from SV40-transformed human or rat cells, Ad5-transformed human cells and several spontaneous human or mouse tumor cells. Chromosomes from normal diploid cells do not show any such transforming activity. As judged from the number of colonies formed in selective medium, the efficiency of transformation is, with some exceptions, of the order of 10(-5)--10(-6) and is generally higher for homologous than for heterologous transfers. A fraction of the colonies demonstrate abortive transformation. Nevertheless, using chromosomes from all but one donor cell population, at least one transferent cell line expressing a stable transformed phenotype has been established. Our results demonstrate that transformation of normal diploid cells by a presumptive chromosome-mediated gene transfer can be obtained with a variety of donor and recipient cells.", "contents": "Transformation of normal diploid cells by isolated metaphase chromosomes of virus-transformed or spontaneous tumor cells. Normal diploid human cells with a limited life-span in culture, as well as primary or secondary cell cultures of mouse or rat embryos, can be transformed in vitro (i.e. grow in soft-agar or low-serum medium) after a single exposure to metaphase chromosomes from SV40-transformed human or rat cells, Ad5-transformed human cells and several spontaneous human or mouse tumor cells. Chromosomes from normal diploid cells do not show any such transforming activity. As judged from the number of colonies formed in selective medium, the efficiency of transformation is, with some exceptions, of the order of 10(-5)--10(-6) and is generally higher for homologous than for heterologous transfers. A fraction of the colonies demonstrate abortive transformation. Nevertheless, using chromosomes from all but one donor cell population, at least one transferent cell line expressing a stable transformed phenotype has been established. Our results demonstrate that transformation of normal diploid cells by a presumptive chromosome-mediated gene transfer can be obtained with a variety of donor and recipient cells."}
{"id": "PMID:217804", "title": "Hypercalcaemia, hyperphosphataemia and cytoplasmic inclusions in a patient with chronic lymphocytic leukaemia.", "content": "The history of a patient with chronic lymphocytic leukaemia (CLL), known for ten years, is presented. During the terminal stage of the disease, she developed hypercalcaemia and hyperphosphataemia. The peripheral blood and lymph node lymphocytes contained crystalline inclusions in the dilated cisterns of the endoplasmic reticulum. The possible mechanism of hypercalcaemia and hyperphosphataemia and the significance of the crystalline inclusion are discussed.", "contents": "Hypercalcaemia, hyperphosphataemia and cytoplasmic inclusions in a patient with chronic lymphocytic leukaemia. The history of a patient with chronic lymphocytic leukaemia (CLL), known for ten years, is presented. During the terminal stage of the disease, she developed hypercalcaemia and hyperphosphataemia. The peripheral blood and lymph node lymphocytes contained crystalline inclusions in the dilated cisterns of the endoplasmic reticulum. The possible mechanism of hypercalcaemia and hyperphosphataemia and the significance of the crystalline inclusion are discussed."}
{"id": "PMID:217805", "title": "Identification and characterization of melanin in tissues and body fluids.", "content": "A new method for the unambiguous identification of melanin in biological materials has been developed. It may also be used to differentiate between melanins from various tissues and with various properties. The method is based on the detection and characterization of the free radicals in melanin by Electron Spin Resonance Spectroscopy. Applications of this approach include the identification of microscopically undetectable melanin in amelanotic melanomas and identification of the nature of the pigment in the Dubin-Johnson Syndrome.", "contents": "Identification and characterization of melanin in tissues and body fluids. A new method for the unambiguous identification of melanin in biological materials has been developed. It may also be used to differentiate between melanins from various tissues and with various properties. The method is based on the detection and characterization of the free radicals in melanin by Electron Spin Resonance Spectroscopy. Applications of this approach include the identification of microscopically undetectable melanin in amelanotic melanomas and identification of the nature of the pigment in the Dubin-Johnson Syndrome."}
{"id": "PMID:217806", "title": "The nucleoside phosphatase method as a marker for the recognition of the autochthonous plexuses in blood vessel walls and the possible connection of the latter with acupuncture mechanisms.", "content": "The innervation of the blood vessels of the palatal mucosa of the frog is investigated histochemically. Besides vaso-motor nerves, fibers from the autochthonous plexuses also invest the vessels. Electron microscope studies of the latter show them to be non-nervous in structure contrary to previous belief. It is suggested they may influence vessels in a humoral manner and possibly play a part in acupuncture effector mechanisms. The electron micrographs are considered to reveal structure previously designated \"terminal reticulum\".", "contents": "The nucleoside phosphatase method as a marker for the recognition of the autochthonous plexuses in blood vessel walls and the possible connection of the latter with acupuncture mechanisms. The innervation of the blood vessels of the palatal mucosa of the frog is investigated histochemically. Besides vaso-motor nerves, fibers from the autochthonous plexuses also invest the vessels. Electron microscope studies of the latter show them to be non-nervous in structure contrary to previous belief. It is suggested they may influence vessels in a humoral manner and possibly play a part in acupuncture effector mechanisms. The electron micrographs are considered to reveal structure previously designated \"terminal reticulum\"."}
{"id": "PMID:217807", "title": "Contribution to the problem of the so-called nonpathogenic amoebae in the intestine of man.", "content": "Among 10,418 patients of a Prague hospital, a plain infection with intestinal parasitic protozoans was identified in 1,319 persons (12.7%). Of these, 3.5% were  infested with Giardia intestinalis, 0.3% with Entamoeba histolytica forma minuta, 5.7% with Endolimax nana. We evaluated the frequency of findings of protozoans in various clinical diagnoses. A statistically significant increase in frequency was recorded for E. nana in diagnoses of eosinophilia, giardiasis, amoebiasis and helminthiasis. A slight increase above the average was found for Entamoeba coli in diagnoses of giardiasis and helminthiasis. Most cases of infection with Entamoeba histolytica were associated with a stay abroad. No increase in the frequency of these protozoans was recorded for patients with diarrhea. An analysis of the results indicated that a nonpathogenic amoeba might participate in the origin of intestinal disorders in man.", "contents": "Contribution to the problem of the so-called nonpathogenic amoebae in the intestine of man. Among 10,418 patients of a Prague hospital, a plain infection with intestinal parasitic protozoans was identified in 1,319 persons (12.7%). Of these, 3.5% were  infested with Giardia intestinalis, 0.3% with Entamoeba histolytica forma minuta, 5.7% with Endolimax nana. We evaluated the frequency of findings of protozoans in various clinical diagnoses. A statistically significant increase in frequency was recorded for E. nana in diagnoses of eosinophilia, giardiasis, amoebiasis and helminthiasis. A slight increase above the average was found for Entamoeba coli in diagnoses of giardiasis and helminthiasis. Most cases of infection with Entamoeba histolytica were associated with a stay abroad. No increase in the frequency of these protozoans was recorded for patients with diarrhea. An analysis of the results indicated that a nonpathogenic amoeba might participate in the origin of intestinal disorders in man."}
{"id": "PMID:217809", "title": "[Anti-D prophylaxis after abortions and interruptions].", "content": "In almost every pregnancy feto-maternal transfusions occur. From the 6th week of pregnancy, blood containing Rhesus antigens may be infused into the maternal circulation and cause sensitization. In case of miscarriage, abortion, ectopic pregnancy and cystic mole the chance of fetomaternal transfusion followed by sensitization of the mother is significantly increased. Therefore immunoprophylaxis with anti-D-immunoglobins should be performed in all these cases.", "contents": "[Anti-D prophylaxis after abortions and interruptions]. In almost every pregnancy feto-maternal transfusions occur. From the 6th week of pregnancy, blood containing Rhesus antigens may be infused into the maternal circulation and cause sensitization. In case of miscarriage, abortion, ectopic pregnancy and cystic mole the chance of fetomaternal transfusion followed by sensitization of the mother is significantly increased. Therefore immunoprophylaxis with anti-D-immunoglobins should be performed in all these cases."}
{"id": "PMID:217810", "title": "Antilipolytic nature of gut GLI, and mode of action of two highly potent intestinal lipolytic species in birds.", "content": "Three major lipolytic factors, termed peaks 1, 2 and 3, according to their elution sequence from Biogel P6 columns, have been identified in duck intestinal extracts. The small molecular weight peaks 2 and 3, were even more lipolytically potent on chick adipocytes than pancreatic glucagon; peak 1, called gut GLI, because of its cross-reactivity in a radioimmunoassay for glucagon, modified the lipolytic activity of peak 2 and pancreatic glucagon. It did so by modifying their capacity to stimulate cyclic AMP production. Peaks 2 and 3 exert their lipolytic effects via different intermediary pathways: only peak 2 induced the formation of cyclic AMP. Insulin in birds is devoid of any antilipolytic activity; this fundamental role may be assumed by gut GLI.", "contents": "Antilipolytic nature of gut GLI, and mode of action of two highly potent intestinal lipolytic species in birds. Three major lipolytic factors, termed peaks 1, 2 and 3, according to their elution sequence from Biogel P6 columns, have been identified in duck intestinal extracts. The small molecular weight peaks 2 and 3, were even more lipolytically potent on chick adipocytes than pancreatic glucagon; peak 1, called gut GLI, because of its cross-reactivity in a radioimmunoassay for glucagon, modified the lipolytic activity of peak 2 and pancreatic glucagon. It did so by modifying their capacity to stimulate cyclic AMP production. Peaks 2 and 3 exert their lipolytic effects via different intermediary pathways: only peak 2 induced the formation of cyclic AMP. Insulin in birds is devoid of any antilipolytic activity; this fundamental role may be assumed by gut GLI."}
{"id": "PMID:217811", "title": "Development of hyperlipidemia associated with increased lipolytic response of isolated adipose tissue cells following prolonged stimulation by an ectopic pituitary tumor.", "content": "Implantation of MtT-F4 tumor, a mammotropic tumor that secretes large quantities of ACTH, GH and prolactin, into male Fisher rats induced the development of hyperlipidemia. Free fatty acid, triglyceride and cholesterol levels in the plasma were significantly increased at 31 days after tumor implantation. Blood glucose and glycerol levels remained normal, while uric acid concentration in the blood was significantly decreased. The lipolytic response of isolated adipose tissue cells to ACTH was significantly higher in cells derived from rats bearing an MtT-F4 tumor for 31 days than from their corresponding controls. However, the activity of adenylate cyclase in fat cells stimulated with ACTH was not significantly higher in cells derived from tumor bearing rats than in cells from control rats.", "contents": "Development of hyperlipidemia associated with increased lipolytic response of isolated adipose tissue cells following prolonged stimulation by an ectopic pituitary tumor. Implantation of MtT-F4 tumor, a mammotropic tumor that secretes large quantities of ACTH, GH and prolactin, into male Fisher rats induced the development of hyperlipidemia. Free fatty acid, triglyceride and cholesterol levels in the plasma were significantly increased at 31 days after tumor implantation. Blood glucose and glycerol levels remained normal, while uric acid concentration in the blood was significantly decreased. The lipolytic response of isolated adipose tissue cells to ACTH was significantly higher in cells derived from rats bearing an MtT-F4 tumor for 31 days than from their corresponding controls. However, the activity of adenylate cyclase in fat cells stimulated with ACTH was not significantly higher in cells derived from tumor bearing rats than in cells from control rats."}
{"id": "PMID:217814", "title": "Isolation of the globular region of the subcomponent q of the C1 component of complement.", "content": "Digestion after heat treatment of the subcomponent q of the C1 component of complement by collagenase leads to the isolation of the globular region of the protein. This product ('heads') is composed of three chains giving an overall molecular weight of about 57000. About half of the collagen-like region present in C1 q is lost after digestion. The 'heads' are shown to be soluble and hemolytically active products.", "contents": "Isolation of the globular region of the subcomponent q of the C1 component of complement. Digestion after heat treatment of the subcomponent q of the C1 component of complement by collagenase leads to the isolation of the globular region of the protein. This product ('heads') is composed of three chains giving an overall molecular weight of about 57000. About half of the collagen-like region present in C1 q is lost after digestion. The 'heads' are shown to be soluble and hemolytically active products."}
{"id": "PMID:217815", "title": "Covalent cross-linking of photosensitive phospholipids to human serum high density apolipoproteins (apoHDL).", "content": "Human serum high density apolipoproteins were reassociated with three different lecithin species substituted with radioactively labelled photosensitive azido fatty acids, bis([3H]-16-azidopalmitoyl)-, bis([3H]12-azidooleoyl)- and bis([3H]18-azidolinoleoyl)glycerophosphocholine. The lipoprotein particles were reconstituted from a mixture of azido-labelled phosphatidylcholine and non-labelled dioleoylglycerophosphocholine (1:9). Excess lipid was separated from the homogeneous particles by Bio-Gel A-5m. The molecular weight, stoichiometry, fluorescence and circular dichroism of the reconstituted particles were determined before and after photoactivation with covalent cross-linking of the phospholipids with the apoproteins. The physical parameters of the reconstituted lipoproteins remained unperturbed by the cross-linking reaction between the generated nitrenes and apolipoprotein A-I and A-II. Thus the hydrophobic interactions of the phospholipid molecules with the apoproteins have been proved for the first time by a chemical method.", "contents": "Covalent cross-linking of photosensitive phospholipids to human serum high density apolipoproteins (apoHDL). Human serum high density apolipoproteins were reassociated with three different lecithin species substituted with radioactively labelled photosensitive azido fatty acids, bis([3H]-16-azidopalmitoyl)-, bis([3H]12-azidooleoyl)- and bis([3H]18-azidolinoleoyl)glycerophosphocholine. The lipoprotein particles were reconstituted from a mixture of azido-labelled phosphatidylcholine and non-labelled dioleoylglycerophosphocholine (1:9). Excess lipid was separated from the homogeneous particles by Bio-Gel A-5m. The molecular weight, stoichiometry, fluorescence and circular dichroism of the reconstituted particles were determined before and after photoactivation with covalent cross-linking of the phospholipids with the apoproteins. The physical parameters of the reconstituted lipoproteins remained unperturbed by the cross-linking reaction between the generated nitrenes and apolipoprotein A-I and A-II. Thus the hydrophobic interactions of the phospholipid molecules with the apoproteins have been proved for the first time by a chemical method."}
{"id": "PMID:217818", "title": "Guinea pig cell-mediated tumor immunity: the chromium release assay detects both cytolysis and serum blocking for syngeneic chemically-induced tumors.", "content": "The chromium release test (CRT) was used to assess cell-mediated immunity to syngeneic, chemically-induced tumors in guinea pigs. The animal models were Sewall Wright strain 13 guinea pigs with 3-methyl-cholanthrene (MCA)-induced fibrosarcomas and strain 2 guinea pigs with diethylnitrosamine (DEN)-induced hepatocarcinomas. Regional lymph node cells were significantly cytolytic for the immunizing tumors, specifically so for three of the four tumors, and tumor-bearer sera could significantly block cytolysis. The two DEN-induced strain 2 hepatomas, line 1 and line 10, are antigenically distinct by the CRT but the two MCA-induced tumors have tumor specific antigens as well as a common, cross-reactive antigen.", "contents": "Guinea pig cell-mediated tumor immunity: the chromium release assay detects both cytolysis and serum blocking for syngeneic chemically-induced tumors. The chromium release test (CRT) was used to assess cell-mediated immunity to syngeneic, chemically-induced tumors in guinea pigs. The animal models were Sewall Wright strain 13 guinea pigs with 3-methyl-cholanthrene (MCA)-induced fibrosarcomas and strain 2 guinea pigs with diethylnitrosamine (DEN)-induced hepatocarcinomas. Regional lymph node cells were significantly cytolytic for the immunizing tumors, specifically so for three of the four tumors, and tumor-bearer sera could significantly block cytolysis. The two DEN-induced strain 2 hepatomas, line 1 and line 10, are antigenically distinct by the CRT but the two MCA-induced tumors have tumor specific antigens as well as a common, cross-reactive antigen."}
{"id": "PMID:217825", "title": "Effect of chronic Trypanosoma brucei infection on the course of louping ill virus infection in mice.", "content": "The course of louping-ill virus infection in mice chronically infected with Trypanosoma brucei was investigated. The mean survival time of mice infected with virus alone was 10.2 days, compared to 12.8 days in mice infected with T. brucei 14 days before virus challenge, and the cumulative mortality in the two groups was 62.5 and 90%, respectively. Virus was only inconsistently detected in the blood of mice given virus alone but was regularly present at high titers for up to 12 days in the blood of mice previously infected with T. brucei. Titers of virus in brains were also higher in dually infected mice, and encephalitis was of greater severity. These results indicate that the immunosuppressive effect of chronic trypanosomiasis may markedly increase susceptibility to acute virus infection. In addition, it is concluded that vector-vertebrate relationships of arthropod-transmitted viruses may be altered by concurrent trypanosome infection.", "contents": "Effect of chronic Trypanosoma brucei infection on the course of louping ill virus infection in mice. The course of louping-ill virus infection in mice chronically infected with Trypanosoma brucei was investigated. The mean survival time of mice infected with virus alone was 10.2 days, compared to 12.8 days in mice infected with T. brucei 14 days before virus challenge, and the cumulative mortality in the two groups was 62.5 and 90%, respectively. Virus was only inconsistently detected in the blood of mice given virus alone but was regularly present at high titers for up to 12 days in the blood of mice previously infected with T. brucei. Titers of virus in brains were also higher in dually infected mice, and encephalitis was of greater severity. These results indicate that the immunosuppressive effect of chronic trypanosomiasis may markedly increase susceptibility to acute virus infection. In addition, it is concluded that vector-vertebrate relationships of arthropod-transmitted viruses may be altered by concurrent trypanosome infection."}
{"id": "PMID:217826", "title": "Lymphocyte proliferative response to viral antigen in pigs infected with transmissible gastroenteritis virus.", "content": "Development and sequence of lymphocytes reactive to viral antigen in Peyer's patches, mesenteric lymph nodes, spleen, and peripheral blood of pigs orally inoculated with transmissible gastroenteritis virus were investigated by a lymphocyte proliferative assay. Lymphocytes reactive to the viral antigen were first detected in all the tissues of pigs tested on postinoculation day 7. Thereafter, they increased in proliferative reactivity and reached a maximal amount on postinoculation days 10 to 14. Antigen-reactive cells were persistently demonstrated in Peyer's patches and mesenteric lymph nodes for at least 110 days after inoculation, although lymphocytes decreased a little in reactivity to the viral antigen with the lapse of time. On the other hand, splenic and peripheral blood cells were found to have only transient proliferative reactivity. No antigen-reactive cells were detected in spleen or peripheral blood after postinoculation days 20 to 30. Lymphocytes decreased remarkably in reactivity to the viral antigen and phytohemagglutinin when treated with anti-porcine thymocyte serum and complement. Their reactivity to lipopolysaccharides was hardly affected by the treatment. Cells harvested on postinoculation days 45 to 60, however, responded a little to the viral antigen even after they were treated with anti-porcine thymocyte serum and complement. Lymphocytes reactive to the viral antigen and phytohemagglutinin belonged mainly to the erythrocyte rosette-forming cell fraction, whereas those reactive to lipopolysaccharides were mostly found in the rosette-nonforming cell fraction.", "contents": "Lymphocyte proliferative response to viral antigen in pigs infected with transmissible gastroenteritis virus. Development and sequence of lymphocytes reactive to viral antigen in Peyer's patches, mesenteric lymph nodes, spleen, and peripheral blood of pigs orally inoculated with transmissible gastroenteritis virus were investigated by a lymphocyte proliferative assay. Lymphocytes reactive to the viral antigen were first detected in all the tissues of pigs tested on postinoculation day 7. Thereafter, they increased in proliferative reactivity and reached a maximal amount on postinoculation days 10 to 14. Antigen-reactive cells were persistently demonstrated in Peyer's patches and mesenteric lymph nodes for at least 110 days after inoculation, although lymphocytes decreased a little in reactivity to the viral antigen with the lapse of time. On the other hand, splenic and peripheral blood cells were found to have only transient proliferative reactivity. No antigen-reactive cells were detected in spleen or peripheral blood after postinoculation days 20 to 30. Lymphocytes decreased remarkably in reactivity to the viral antigen and phytohemagglutinin when treated with anti-porcine thymocyte serum and complement. Their reactivity to lipopolysaccharides was hardly affected by the treatment. Cells harvested on postinoculation days 45 to 60, however, responded a little to the viral antigen even after they were treated with anti-porcine thymocyte serum and complement. Lymphocytes reactive to the viral antigen and phytohemagglutinin belonged mainly to the erythrocyte rosette-forming cell fraction, whereas those reactive to lipopolysaccharides were mostly found in the rosette-nonforming cell fraction."}
{"id": "PMID:217827", "title": "Persistence of avian oncoviruses in chicken macrophages.", "content": "Inoculation of avian oncoviruses into 1- to 2-month old chickens led to a rapid production of antiviral humoral antibodies. Under these conditions it was found that avian leukosis viruses are sequestered in macrophages of peripheral blood, in which they can persist for a long period of time (up to about 3 years). In contrast, avian sarcoma viruses were never found in macrophages from chickens during the progression of sarcomas or after regression of the tumors.", "contents": "Persistence of avian oncoviruses in chicken macrophages. Inoculation of avian oncoviruses into 1- to 2-month old chickens led to a rapid production of antiviral humoral antibodies. Under these conditions it was found that avian leukosis viruses are sequestered in macrophages of peripheral blood, in which they can persist for a long period of time (up to about 3 years). In contrast, avian sarcoma viruses were never found in macrophages from chickens during the progression of sarcomas or after regression of the tumors."}
{"id": "PMID:217828", "title": "Host defenses in herpes simplex infections of the nervous system: effect of antibody on disease and viral spread.", "content": "BALB/c mice passively immunized with antibody to herpes simplex virus type 1 and challenged in the footpad with 10(5.7) plaque-forming units of herpes simplex virus type 1 were shown to be protected from neurological disease and death compared with control mice treated with normal serum or antibody to Sindbis virus. One hundred percent of untreated mice had virus recoverable from dorsal root ganglia by 48 h after infection. Whereas amputation of the infected limb at 48 h had no effect, antibody administration (resulting in titers of 1:8 and 1:16) was found to prevent acute neurological disease if administered no later than 48 h after infection. Antibody also restricted the extent of latent infection in the lumbosacral ganglia. The data provide strong evidence that antibody is effective in preventing spread of virus both in the peripheral nervous system and in central nervous system (spinal cord) tissue.", "contents": "Host defenses in herpes simplex infections of the nervous system: effect of antibody on disease and viral spread. BALB/c mice passively immunized with antibody to herpes simplex virus type 1 and challenged in the footpad with 10(5.7) plaque-forming units of herpes simplex virus type 1 were shown to be protected from neurological disease and death compared with control mice treated with normal serum or antibody to Sindbis virus. One hundred percent of untreated mice had virus recoverable from dorsal root ganglia by 48 h after infection. Whereas amputation of the infected limb at 48 h had no effect, antibody administration (resulting in titers of 1:8 and 1:16) was found to prevent acute neurological disease if administered no later than 48 h after infection. Antibody also restricted the extent of latent infection in the lumbosacral ganglia. The data provide strong evidence that antibody is effective in preventing spread of virus both in the peripheral nervous system and in central nervous system (spinal cord) tissue."}
{"id": "PMID:217829", "title": "Susceptibility of lymphoblastoid cells to infection with human cytomegalovirus.", "content": "Human lymphoblastoid cells of B- and T-cell origin were examined for their in vitro susceptibility to infection with human cytomegalovirus (CMV). Results of infectious-center assays, at virus to cell ratios of 10, indicated that in each of the lymphoblastoid cell lines tested less than 1% of the cells produced infectious virus. Under these conditions, CMV specific antigens were undetectable. Infection of lymphoblastoid cells with CMV resulted in atypical virus growth curves similar to those obtained with persistently infected human embryonic kidney cells. Although some variation existed in the relative sensitivity of lymphoblasts, cells of B (Raji, P3J-HR-1, RPMI 8226) and T (CCRF-CEM) origin were susceptible to infection with CMV. Variation in the sensitivity of lymphoblasts to CMV infection did not correlate with differences in virus adsorption or the presence of Epstein-Barr virus deoxyribonucleic acid. These studies suggest that human lymphoblastoid cells could serve as a model to examine persistent CMV infection in lymphoid cells of various origin.", "contents": "Susceptibility of lymphoblastoid cells to infection with human cytomegalovirus. Human lymphoblastoid cells of B- and T-cell origin were examined for their in vitro susceptibility to infection with human cytomegalovirus (CMV). Results of infectious-center assays, at virus to cell ratios of 10, indicated that in each of the lymphoblastoid cell lines tested less than 1% of the cells produced infectious virus. Under these conditions, CMV specific antigens were undetectable. Infection of lymphoblastoid cells with CMV resulted in atypical virus growth curves similar to those obtained with persistently infected human embryonic kidney cells. Although some variation existed in the relative sensitivity of lymphoblasts, cells of B (Raji, P3J-HR-1, RPMI 8226) and T (CCRF-CEM) origin were susceptible to infection with CMV. Variation in the sensitivity of lymphoblasts to CMV infection did not correlate with differences in virus adsorption or the presence of Epstein-Barr virus deoxyribonucleic acid. These studies suggest that human lymphoblastoid cells could serve as a model to examine persistent CMV infection in lymphoid cells of various origin."}
{"id": "PMID:217830", "title": "Replication of herpes simplex virus type 1 in macrophages from resistant and susceptible mice.", "content": "Studies were carried out to determine whether the in vitro capacity of adherent peritoneal cells to replicate herpes simplex virus type 1 (HSV-1) might correlate with the in vivo susceptibility of mice genetically resistant, moderately susceptible, or very susceptible to HSV-1 infection. Unstimulated and proteose peptone-stimulated monolayers restricted viral replication when infected immediately, but replicated HSV-1 when infected after 3 to 7 days of culture. Macrophages from resistant C57Bl/6 mice restricted HSV-1 replication significantly better than cells from susceptible mice. This function did not segregate with resistance, since macrophages from resistant F1 mice failed to restrict HSV-1 replication. Induction of peritoneal exudate cells with thioglycolate yielded cells capable of replicating HSV-1 when infected immediately after plating and after 4 days of culture.", "contents": "Replication of herpes simplex virus type 1 in macrophages from resistant and susceptible mice. Studies were carried out to determine whether the in vitro capacity of adherent peritoneal cells to replicate herpes simplex virus type 1 (HSV-1) might correlate with the in vivo susceptibility of mice genetically resistant, moderately susceptible, or very susceptible to HSV-1 infection. Unstimulated and proteose peptone-stimulated monolayers restricted viral replication when infected immediately, but replicated HSV-1 when infected after 3 to 7 days of culture. Macrophages from resistant C57Bl/6 mice restricted HSV-1 replication significantly better than cells from susceptible mice. This function did not segregate with resistance, since macrophages from resistant F1 mice failed to restrict HSV-1 replication. Induction of peritoneal exudate cells with thioglycolate yielded cells capable of replicating HSV-1 when infected immediately after plating and after 4 days of culture."}
{"id": "PMID:217831", "title": "Specificity of response to viral proteins in horses infected with equine infectious anemia virus.", "content": "Three structural proteins of equine infectious anemia virus were purified, labeled with 125I, and utilized in radioimmunoassays with horse sera and antisera to heterologous retroviruses. Whereas radioimmunoassay titers for the major protein, p25, were 500- to 1,000-fold higher than titers in immunodiffusion, for clinical purposes these two procedures were equivalent. Antibodies to two low-molecular-weight proteins, p12 and p10, were also found in infected horses, but with a lower frequency and lower titers. As a rule, only sera positive for p25 also contained antibody to p12 and p10. Antisera to the major structural protein of other retroviruses did not precipitate equine infectious anemia virus p25. These sera include antibody to mammalian type C viruses, bovine leukemia virus, visna virus, mouse mammary tumor virus, squirrel monkey retrovirus, and Mason-Pfizer monkey virus.", "contents": "Specificity of response to viral proteins in horses infected with equine infectious anemia virus. Three structural proteins of equine infectious anemia virus were purified, labeled with 125I, and utilized in radioimmunoassays with horse sera and antisera to heterologous retroviruses. Whereas radioimmunoassay titers for the major protein, p25, were 500- to 1,000-fold higher than titers in immunodiffusion, for clinical purposes these two procedures were equivalent. Antibodies to two low-molecular-weight proteins, p12 and p10, were also found in infected horses, but with a lower frequency and lower titers. As a rule, only sera positive for p25 also contained antibody to p12 and p10. Antisera to the major structural protein of other retroviruses did not precipitate equine infectious anemia virus p25. These sera include antibody to mammalian type C viruses, bovine leukemia virus, visna virus, mouse mammary tumor virus, squirrel monkey retrovirus, and Mason-Pfizer monkey virus."}
{"id": "PMID:217832", "title": "Assessment of coxsackievirus B3 ts mutants for induction of myocarditis in a murine model.", "content": "Ten temperature-sensitive (ts) mutants isolated from a myocarditis-inducing wild-type (WT) coxsackievirus B3 parent did not induce myocarditis in adolescent CD-1 mice. An avirulent prototype ts mutant from one of the three complementation groups adsorbed to murine cardiac tissue, as did WT virus. Heart tissues from mice inoculated with WT virus contained 100- to 1,000-fold more virus than heart tissues from mice inoculated with any of the three prototype ts mutants. WT virus exhibited a greater capsid stability and a higher efficiency of replication at 37 degrees C than any of the three prototype ts mutants. All three prototype ts mutants induced less interferon in vivo than WT virus. Cell-mediated immune responses, assessed by the cell migration inhibition assay, were different in mice inoculated with WT virus when compared to ts 5 mutant virus. Peritoneal exudate cells from mice inoculated with WT but not ts 5 virus reacted specifically against antigens in WT virus HeLa cell lysates and antigens extracted with KCl from cardiac tissues of mice inoculated with WT virus. Cardiac tissues of mice inoculated with WT but not ts 5 virus contained KCl-extractable antigens which were able to specifically inhibit the migration of peritoneal exudate cells taken from mice immunized with WT virus. Therefore, ts 5 neither elicited a measurable cell-mediated immune response nor induced antigens in cardiac tissues which were immunoreactive with sensitized-(WT virus)-peritoneal exudate cells. Of 9 revertant viruses isolated from the 10 ts mutants, 5 showed covariance in ability to replicate at 39.5 degrees C and capacity for induction of myocarditis. Some revertants exhibited a reduced capsid thermostability compared to WT virus but yet retained the capacity for induction of myocarditis. The data suggest that induction of myocarditis by coxsackievirus B3 variants depends on a combination of several variables, including capsid stability, capacity for replication at 37 degrees C, and expression of the three identified genes. All three prototype ts mutants served as vaccine viruses in preventing myocarditis in adolescent mice subsequently challenged with WT virus. However, all three prototype ts mutants and their revertant variants retained partial to complete lethality in CD-1 neonates.", "contents": "Assessment of coxsackievirus B3 ts mutants for induction of myocarditis in a murine model. Ten temperature-sensitive (ts) mutants isolated from a myocarditis-inducing wild-type (WT) coxsackievirus B3 parent did not induce myocarditis in adolescent CD-1 mice. An avirulent prototype ts mutant from one of the three complementation groups adsorbed to murine cardiac tissue, as did WT virus. Heart tissues from mice inoculated with WT virus contained 100- to 1,000-fold more virus than heart tissues from mice inoculated with any of the three prototype ts mutants. WT virus exhibited a greater capsid stability and a higher efficiency of replication at 37 degrees C than any of the three prototype ts mutants. All three prototype ts mutants induced less interferon in vivo than WT virus. Cell-mediated immune responses, assessed by the cell migration inhibition assay, were different in mice inoculated with WT virus when compared to ts 5 mutant virus. Peritoneal exudate cells from mice inoculated with WT but not ts 5 virus reacted specifically against antigens in WT virus HeLa cell lysates and antigens extracted with KCl from cardiac tissues of mice inoculated with WT virus. Cardiac tissues of mice inoculated with WT but not ts 5 virus contained KCl-extractable antigens which were able to specifically inhibit the migration of peritoneal exudate cells taken from mice immunized with WT virus. Therefore, ts 5 neither elicited a measurable cell-mediated immune response nor induced antigens in cardiac tissues which were immunoreactive with sensitized-(WT virus)-peritoneal exudate cells. Of 9 revertant viruses isolated from the 10 ts mutants, 5 showed covariance in ability to replicate at 39.5 degrees C and capacity for induction of myocarditis. Some revertants exhibited a reduced capsid thermostability compared to WT virus but yet retained the capacity for induction of myocarditis. The data suggest that induction of myocarditis by coxsackievirus B3 variants depends on a combination of several variables, including capsid stability, capacity for replication at 37 degrees C, and expression of the three identified genes. All three prototype ts mutants served as vaccine viruses in preventing myocarditis in adolescent mice subsequently challenged with WT virus. However, all three prototype ts mutants and their revertant variants retained partial to complete lethality in CD-1 neonates."}
{"id": "PMID:217833", "title": "Cellular interactions determine the rate and degree of interferon action.", "content": "The rate and degree of interferon action on mouse embryo (ME), mouse L, and human amnion (WISH) cells were found to be dependent on the cell density. The most precipitous drop in interferon action occurred just below cell confluency. This effect was shown with both vesicular stomatitis virus and Sindbis virus and at both constant and variable input multiplicities of infection. At both \"high\" and \"low\" cell densities, cells attached to a surface develop viral resistance faster than suspended cells. These data indicate that either cell contact or close cell proximity is required for maximal interferon activity. These results are discussed in relation to interferon-induced transfer of viral resistance.", "contents": "Cellular interactions determine the rate and degree of interferon action. The rate and degree of interferon action on mouse embryo (ME), mouse L, and human amnion (WISH) cells were found to be dependent on the cell density. The most precipitous drop in interferon action occurred just below cell confluency. This effect was shown with both vesicular stomatitis virus and Sindbis virus and at both constant and variable input multiplicities of infection. At both \"high\" and \"low\" cell densities, cells attached to a surface develop viral resistance faster than suspended cells. These data indicate that either cell contact or close cell proximity is required for maximal interferon activity. These results are discussed in relation to interferon-induced transfer of viral resistance."}
{"id": "PMID:217834", "title": "Myeloperoxidase, hydrogen peroxide, chloride antimicrobial system: nitrogen-chlorine derivatives of bacterial components in bactericidal action against Escherichia coli.", "content": "In the presence of Escherichia coli, myeloperoxidase-catalyzed oxidation of chloride ion resulted in formation of long-lived chloramine and/or chloramide derivatives of bacterial components. The same amount of these nitrogen-chlorine (N-Cl) derivatives was obtained with either hypochlorous acid (HOCl) or the myeloperoxidase system, indicating that myeloperoxidase catalyzed the oxidation of chloride to HOCl. Identical killing was obtained with HOCl or the myeloperoxidase system. About 30 to 50% of the oxidizing equivalents of HOCl were detected as N-Cl derivatives of peptides or peptide fragments that were released from the bacteria. The apparent molecular weight distribution of the peptides decreased with increasing amounts of HOCl, suggesting that peptides were fragmented by oxidative cleavage of chloramide derivatives of peptide bonds. The remaining 50 to 70% of the oxidizing equivalents of HOCl were rapidly consumed in peptide bond cleavage or the oxidation of other bacterial components. There was a close correspondence between the oxidation of bacterial sulfhydryls and bactericidal action. The N-Cl derivatives were lost and the oxidation of bacterial sulfhydryls increased over a period of several h at 37 degrees C. These changes were accompanied by increased killing. The increase in sulfhydryl oxidation and killing could be prevented by washing the bacteria to remove the N-Cl derivatives. Therefore, the N-Cl derivatives could oxidize bacterial components long after the myeloperoxidase-catalyzed oxidation of chloride was complete.", "contents": "Myeloperoxidase, hydrogen peroxide, chloride antimicrobial system: nitrogen-chlorine derivatives of bacterial components in bactericidal action against Escherichia coli. In the presence of Escherichia coli, myeloperoxidase-catalyzed oxidation of chloride ion resulted in formation of long-lived chloramine and/or chloramide derivatives of bacterial components. The same amount of these nitrogen-chlorine (N-Cl) derivatives was obtained with either hypochlorous acid (HOCl) or the myeloperoxidase system, indicating that myeloperoxidase catalyzed the oxidation of chloride to HOCl. Identical killing was obtained with HOCl or the myeloperoxidase system. About 30 to 50% of the oxidizing equivalents of HOCl were detected as N-Cl derivatives of peptides or peptide fragments that were released from the bacteria. The apparent molecular weight distribution of the peptides decreased with increasing amounts of HOCl, suggesting that peptides were fragmented by oxidative cleavage of chloramide derivatives of peptide bonds. The remaining 50 to 70% of the oxidizing equivalents of HOCl were rapidly consumed in peptide bond cleavage or the oxidation of other bacterial components. There was a close correspondence between the oxidation of bacterial sulfhydryls and bactericidal action. The N-Cl derivatives were lost and the oxidation of bacterial sulfhydryls increased over a period of several h at 37 degrees C. These changes were accompanied by increased killing. The increase in sulfhydryl oxidation and killing could be prevented by washing the bacteria to remove the N-Cl derivatives. Therefore, the N-Cl derivatives could oxidize bacterial components long after the myeloperoxidase-catalyzed oxidation of chloride was complete."}
{"id": "PMID:217835", "title": "Murine neurotropic retrovirus spongiform polioencephalomyelopathy: acceleration of disease by virus inoculum concentration.", "content": "A 10-fold reduction in the incubation period of murine neurotropic retrovirus spongiform polioencephalomyelopathy was effected by a 1,000-fold concentration of the cloned virus inoculum.", "contents": "Murine neurotropic retrovirus spongiform polioencephalomyelopathy: acceleration of disease by virus inoculum concentration. A 10-fold reduction in the incubation period of murine neurotropic retrovirus spongiform polioencephalomyelopathy was effected by a 1,000-fold concentration of the cloned virus inoculum."}
{"id": "PMID:217836", "title": "Mecillinam in urinary tract infections and in septicaemia.", "content": "The clinical and bacteriological efficacy as well as the tolerance of mecillinam, a new beta-lactam antibiotic, administered parenterally in a dose of 40 mg/kg body weight, was investigated in 21 hospitalized patients with urinary tract infections or septicaemia. Success, defined as eradication of infecting organisms two to five days after treatment, was found in eight of 16 patients with urinary tract infections. Persistence of the original pathogen after treatment was seen in four patients, all with complicated urinary tract infection. Reinfection was seen in two patients, while the results were unevaluable in two cases. The five patients with septicaemia were all cured of their infection, this result being attributed solely to mecillinam in two cases, while a combined action of mecillinam and another antibiotic produced a cure in the other three cases. Escherichia coli resistant to mecillinam were isolated from two patients with persistence of bacteriuria following mecillinam treatment. Impairment of renal function may have been a contributory factor to the poor treatment response in patients with complicated urinary tract infection. Inasmuch as no important side-effects were recorded and mecillinam appears safe in patients with impaired renal and liver function, a higher dose may be indicated in these more complicated cases.", "contents": "Mecillinam in urinary tract infections and in septicaemia. The clinical and bacteriological efficacy as well as the tolerance of mecillinam, a new beta-lactam antibiotic, administered parenterally in a dose of 40 mg/kg body weight, was investigated in 21 hospitalized patients with urinary tract infections or septicaemia. Success, defined as eradication of infecting organisms two to five days after treatment, was found in eight of 16 patients with urinary tract infections. Persistence of the original pathogen after treatment was seen in four patients, all with complicated urinary tract infection. Reinfection was seen in two patients, while the results were unevaluable in two cases. The five patients with septicaemia were all cured of their infection, this result being attributed solely to mecillinam in two cases, while a combined action of mecillinam and another antibiotic produced a cure in the other three cases. Escherichia coli resistant to mecillinam were isolated from two patients with persistence of bacteriuria following mecillinam treatment. Impairment of renal function may have been a contributory factor to the poor treatment response in patients with complicated urinary tract infection. Inasmuch as no important side-effects were recorded and mecillinam appears safe in patients with impaired renal and liver function, a higher dose may be indicated in these more complicated cases."}
{"id": "PMID:217837", "title": "Rotavirus gastroenteritis in infants and young children.", "content": "The electronmicroscopic examination of stool samples from 18 infants and young children with gastroenteritis, hospitalized at the Clinic of Infectious Diseases in Prague, was carried out. In ten children rotavirus was found in the faeces and the bacteriological findings were negative. Rotavirus particles were aggregated by convalescent child sera and by normal human gamma globulin. The clinical picture was characterized by the sudden onset of vomiting and fever, in one case with febrile convulsions. Diarrhoea was watery and yellow-green, and usually persisted for four to five days. The condition of the children improved rapidly after rehydration and a special diet. Older siblings, and in one family also adult members, were frequently affected.", "contents": "Rotavirus gastroenteritis in infants and young children. The electronmicroscopic examination of stool samples from 18 infants and young children with gastroenteritis, hospitalized at the Clinic of Infectious Diseases in Prague, was carried out. In ten children rotavirus was found in the faeces and the bacteriological findings were negative. Rotavirus particles were aggregated by convalescent child sera and by normal human gamma globulin. The clinical picture was characterized by the sudden onset of vomiting and fever, in one case with febrile convulsions. Diarrhoea was watery and yellow-green, and usually persisted for four to five days. The condition of the children improved rapidly after rehydration and a special diet. Older siblings, and in one family also adult members, were frequently affected."}
{"id": "PMID:217840", "title": "Antigens in penicillin allergy. III. Antigen and antibody levels in mice treated with pure and contaminated penicillins.", "content": "Using a radioimmunoassay, it was shown that commercially available ampicillin preparations often contain penicilloylated high molecular weight impurities. These possess immunological activities and stimulate penicilloyl-specific antibody formation in mice treated according to a therapeutic schedule. Using purified and experimentally contaminated preparations it was also found that exposure of the animals to Escherichia coli and Bordetella pertussis bacteria could increase the antibody formation to small amounts of impurities. In addition, penicilloylated antigen could be recorded in serum from treated animals. The antigen formed by penicilloylation in vivo, however, was very weak and did not induce much antibody formation when injected together with Freund's adjuvant in mice or rabbits.", "contents": "Antigens in penicillin allergy. III. Antigen and antibody levels in mice treated with pure and contaminated penicillins. Using a radioimmunoassay, it was shown that commercially available ampicillin preparations often contain penicilloylated high molecular weight impurities. These possess immunological activities and stimulate penicilloyl-specific antibody formation in mice treated according to a therapeutic schedule. Using purified and experimentally contaminated preparations it was also found that exposure of the animals to Escherichia coli and Bordetella pertussis bacteria could increase the antibody formation to small amounts of impurities. In addition, penicilloylated antigen could be recorded in serum from treated animals. The antigen formed by penicilloylation in vivo, however, was very weak and did not induce much antibody formation when injected together with Freund's adjuvant in mice or rabbits."}
{"id": "PMID:217841", "title": "In vivo suppression of allograft rejection by cyclic AMP increasing agents.", "content": "This study was undertaken to elucidate the possibilities of modulating the survival of allogeneic tissue grafts by administration of cyclic AMP-increasing agents to the graft recipients. Heterotopic grafting of split mouse hearts across a strong H-2 barrier was used. It was found that Vibrio cholerae enterotoxin, which activates adenylate cyclase in mammalian cells, gave a marked prolongation of the graft survival time when given shortly before (but not after) transplantation. Also the administration of a combination of cyclic AMP and theophylline prior to or around transplantation increased graft survival time significantly. In contrast, no effect was obtained with choleragenoid, a membrane-binding cholera toxin analogue devoid of cyclic AMP-increasing activity.", "contents": "In vivo suppression of allograft rejection by cyclic AMP increasing agents. This study was undertaken to elucidate the possibilities of modulating the survival of allogeneic tissue grafts by administration of cyclic AMP-increasing agents to the graft recipients. Heterotopic grafting of split mouse hearts across a strong H-2 barrier was used. It was found that Vibrio cholerae enterotoxin, which activates adenylate cyclase in mammalian cells, gave a marked prolongation of the graft survival time when given shortly before (but not after) transplantation. Also the administration of a combination of cyclic AMP and theophylline prior to or around transplantation increased graft survival time significantly. In contrast, no effect was obtained with choleragenoid, a membrane-binding cholera toxin analogue devoid of cyclic AMP-increasing activity."}
{"id": "PMID:217842", "title": "Stimulatory and inhibitory effects of cyclic AMP on lymphocytes from atopic children.", "content": "The effect of cholera toxin and dibutyryl cAMP on mitogen-activated lymphocytes from atopic and non-atopic individuals was studied. Cholera toxin enhanced stimulation by phytohemagglutinin of cells from small children but not from adults. Dibutyryl cAMP at low concentration (less than 10(-5) M) significantly enhanced the lymphocyte response to mitogens in some, but not all individuals. High concentrations, on the other hand, were consistently inhibitory. In atopic children, the lymphocyte response to T cell mitogen was significantly less stimulated by cholera toxin, and more inhibited by dibutyryl cAMP than the response of cells from non-atopic matched controls. Thus, T cells from atopic individuals appear to have an altered sensitivity to the action of cAMP, possibly resulting in an impaired balance between helper and suppressor T cells. The hypothesis is advanced, that such an altered balance is causally related to hyperproduction of IgE resulting in atopic disease.", "contents": "Stimulatory and inhibitory effects of cyclic AMP on lymphocytes from atopic children. The effect of cholera toxin and dibutyryl cAMP on mitogen-activated lymphocytes from atopic and non-atopic individuals was studied. Cholera toxin enhanced stimulation by phytohemagglutinin of cells from small children but not from adults. Dibutyryl cAMP at low concentration (less than 10(-5) M) significantly enhanced the lymphocyte response to mitogens in some, but not all individuals. High concentrations, on the other hand, were consistently inhibitory. In atopic children, the lymphocyte response to T cell mitogen was significantly less stimulated by cholera toxin, and more inhibited by dibutyryl cAMP than the response of cells from non-atopic matched controls. Thus, T cells from atopic individuals appear to have an altered sensitivity to the action of cAMP, possibly resulting in an impaired balance between helper and suppressor T cells. The hypothesis is advanced, that such an altered balance is causally related to hyperproduction of IgE resulting in atopic disease."}
{"id": "PMID:217843", "title": "Suppression of IgE antibody formation in mice: requirement for T-T lymphocyte interaction.", "content": "Norman SWR mice injected with syngeneic spleen cells from ovalbumin (Ov)-primed mice were unable to make IgE anti-Ov antibodies when challenged with alum-pertussis-Ov. Immune T lymphocytes were shown to be responsible for the inhibitory effects of adoptively transferred spleen cells. Treatment of recipient mice with mild x-irradiation or with cyclophosphamide 2 or 3 days before cell transfer resulted in abrogation of the suppressor effect of immune cells. The injection of T lymphocytes into x-irradiated milce restored the suppressive effect of immune cells. It thus appears that immune T cells provide the stimulus for activation of suppressor T cells of the host. Although the generation of suppression is antigen-specific, the expression of suppression appears to be nonspecific.", "contents": "Suppression of IgE antibody formation in mice: requirement for T-T lymphocyte interaction. Norman SWR mice injected with syngeneic spleen cells from ovalbumin (Ov)-primed mice were unable to make IgE anti-Ov antibodies when challenged with alum-pertussis-Ov. Immune T lymphocytes were shown to be responsible for the inhibitory effects of adoptively transferred spleen cells. Treatment of recipient mice with mild x-irradiation or with cyclophosphamide 2 or 3 days before cell transfer resulted in abrogation of the suppressor effect of immune cells. The injection of T lymphocytes into x-irradiated milce restored the suppressive effect of immune cells. It thus appears that immune T cells provide the stimulus for activation of suppressor T cells of the host. Although the generation of suppression is antigen-specific, the expression of suppression appears to be nonspecific."}
{"id": "PMID:217844", "title": "Alkaline isomerization of horse and yeast cytochromes C. Spectrophotometric and circular dichroism studies.", "content": "Spectrophotometric studies of the alkaline isomerization of horse heart and yeast cytochrome c show that the haemoproteins from Saccharomyces cerevisiae differ significantly from the mammalian cytochrome c. Apparent pKa values of 8.41, 8.40 and 8.73 for isol-1-(the methylated and unmethylated forms) and iso-2-cytochrome c respectively, from baker's yeast were determined and compared with the value of 9.40 found for horse heart cytochrome c. The transitions, measured by observing the decrease of the absorbance at 695 nm as the pH increases, have been found to strictly parallel the decrease in amplitude of the negative circular dichroism band centered at 417 nm. This observation gives additional evidence that this negative band is closely related to the ligation of the heme iron by the sulfur atom of methionine 8u for each of the four haemoproteins examined.", "contents": "Alkaline isomerization of horse and yeast cytochromes C. Spectrophotometric and circular dichroism studies. Spectrophotometric studies of the alkaline isomerization of horse heart and yeast cytochrome c show that the haemoproteins from Saccharomyces cerevisiae differ significantly from the mammalian cytochrome c. Apparent pKa values of 8.41, 8.40 and 8.73 for isol-1-(the methylated and unmethylated forms) and iso-2-cytochrome c respectively, from baker's yeast were determined and compared with the value of 9.40 found for horse heart cytochrome c. The transitions, measured by observing the decrease of the absorbance at 695 nm as the pH increases, have been found to strictly parallel the decrease in amplitude of the negative circular dichroism band centered at 417 nm. This observation gives additional evidence that this negative band is closely related to the ligation of the heme iron by the sulfur atom of methionine 8u for each of the four haemoproteins examined."}
{"id": "PMID:217845", "title": "Volume and polarity changes accompanied by amino acid substitutions in protein evolution.", "content": "We evaluated the volume and polarity changes accompanied by amino acid substitutions along branches of the phylogenetic trees of cytochrome c, myoglobin and hemoglobin alpha and beta chains. In most cases the volume changes accompanied by the substitutions were found to be much larger than the volume of cavities existing in the interior of X-ray-analysed proteins. This implies that the interior of the proteins is very flexible and the necessary space for a larger amino acid residue substitution can be provided by adjusting nearby structures. Also, the volume and polarity changes are not particularly dependent on whether the substituted site is located in the exterior or interior of the proteins. This result supports the concept of the covarions by Fitch and Markowitz, when combined with the known fact that the exterior sites are more variable than the interior ones during protein evolution.", "contents": "Volume and polarity changes accompanied by amino acid substitutions in protein evolution. We evaluated the volume and polarity changes accompanied by amino acid substitutions along branches of the phylogenetic trees of cytochrome c, myoglobin and hemoglobin alpha and beta chains. In most cases the volume changes accompanied by the substitutions were found to be much larger than the volume of cavities existing in the interior of X-ray-analysed proteins. This implies that the interior of the proteins is very flexible and the necessary space for a larger amino acid residue substitution can be provided by adjusting nearby structures. Also, the volume and polarity changes are not particularly dependent on whether the substituted site is located in the exterior or interior of the proteins. This result supports the concept of the covarions by Fitch and Markowitz, when combined with the known fact that the exterior sites are more variable than the interior ones during protein evolution."}
{"id": "PMID:217846", "title": "Isolation and primary structure of adrenocorticotropin from several species of whale.", "content": "The isolation of adrenocorticotropin (ACTH) from fin (Balaenoptera physalus), sei (Blaenoptera borelis) and sperm (Physeter catodon) whale pituitaries is described. Their primary structures have been elucidated by the fluorescein isothiocyanate method and revealed to be identical to the structure of the human hormone. Fin whale exhibited an identical steroidogenic activity to that of the porcine hormone.", "contents": "Isolation and primary structure of adrenocorticotropin from several species of whale. The isolation of adrenocorticotropin (ACTH) from fin (Balaenoptera physalus), sei (Blaenoptera borelis) and sperm (Physeter catodon) whale pituitaries is described. Their primary structures have been elucidated by the fluorescein isothiocyanate method and revealed to be identical to the structure of the human hormone. Fin whale exhibited an identical steroidogenic activity to that of the porcine hormone."}
{"id": "PMID:217847", "title": "Purification and receptor binding properties of complexes between lutropin and monovalent antibodies against its alpha subunit.", "content": "A complex between bovine lutropin (LH) and monovalent antibodies (Fab fragments) directed against its alpha subunit, which is common to the glycoprotein hormones, has been purified by gel filtration and chromatography on concanavalin A-Sepharose. The complex is heterogenous with respect to molecular size; 70--80% of the hormone is complexed with either two or three Fab fragments. The LH-Fab alpha complexes retain only about 13% receptor binding activity as compared to LH when measured in a radioligand receptor assay in which the radiolabeled ligand is human choriogonadotropin. (Use of the human hormone as labeled ligand permits direct measurement of competition between receptor and the bovine complex because the alpha portion of the human hormone does not cross react significantly with antibodies directed against bovine alpha subunits.) Complex formation does not lead to dissociation of the lutropin into its subunits, as shown with a homologous LH-beta immunoassay which distinguishes free beta subunit from intact LH. Complexing of LH with Fab-alpha fragments also causes little or no change in the affinity of the hormone's beta subunit for anti-LH-beta antibodies indicating that significant changes in beta subunit conformation did not occur. The data show that at least two well-separated antigenic regions on the alpha subunit are exposed to the surface in the intact hormone. They are also in agreement with the proposal that the loss of binding activity to receptor is due to steric effects rather than to changes in conformation or dissociation, and that there may be sites on the alpha subunit which interact directly with the receptor.", "contents": "Purification and receptor binding properties of complexes between lutropin and monovalent antibodies against its alpha subunit. A complex between bovine lutropin (LH) and monovalent antibodies (Fab fragments) directed against its alpha subunit, which is common to the glycoprotein hormones, has been purified by gel filtration and chromatography on concanavalin A-Sepharose. The complex is heterogenous with respect to molecular size; 70--80% of the hormone is complexed with either two or three Fab fragments. The LH-Fab alpha complexes retain only about 13% receptor binding activity as compared to LH when measured in a radioligand receptor assay in which the radiolabeled ligand is human choriogonadotropin. (Use of the human hormone as labeled ligand permits direct measurement of competition between receptor and the bovine complex because the alpha portion of the human hormone does not cross react significantly with antibodies directed against bovine alpha subunits.) Complex formation does not lead to dissociation of the lutropin into its subunits, as shown with a homologous LH-beta immunoassay which distinguishes free beta subunit from intact LH. Complexing of LH with Fab-alpha fragments also causes little or no change in the affinity of the hormone's beta subunit for anti-LH-beta antibodies indicating that significant changes in beta subunit conformation did not occur. The data show that at least two well-separated antigenic regions on the alpha subunit are exposed to the surface in the intact hormone. They are also in agreement with the proposal that the loss of binding activity to receptor is due to steric effects rather than to changes in conformation or dissociation, and that there may be sites on the alpha subunit which interact directly with the receptor."}
{"id": "PMID:217850", "title": "[Generalized herpes simplex].", "content": "This report is about a 58-year-old female patient with generalized herpes simplex virus exanthema. The virus was detected not only in the skin eruptions but also in rinsing liquid from the throat. Its typical feature revealed it to be herpes simplex virus Type I. On the basis of similar cases which have been described in literature, we point out that it is necessary to carry out virological and serological tests in cases of uncertain vesico-pustular or erythema exsudativum multiforme like exanthemas. These exanthemas must be separated from the postherpetic erythema exsudativum multiforme because of the identified virus.", "contents": "[Generalized herpes simplex]. This report is about a 58-year-old female patient with generalized herpes simplex virus exanthema. The virus was detected not only in the skin eruptions but also in rinsing liquid from the throat. Its typical feature revealed it to be herpes simplex virus Type I. On the basis of similar cases which have been described in literature, we point out that it is necessary to carry out virological and serological tests in cases of uncertain vesico-pustular or erythema exsudativum multiforme like exanthemas. These exanthemas must be separated from the postherpetic erythema exsudativum multiforme because of the identified virus."}
{"id": "PMID:217851", "title": "[The effect of collagenase inhibition on bullous eruption and healing process in epidermolysis bullosa].", "content": "The collagenase inhibiting effect of erythromycin already observed in vitro was demonstrated also after oral administration of the drug in vivo in one child with epidermolysis bullosa letalis and one child with epidermolysis bullosa dystrophica. Despite inhibition of skin collagenase activity during administration of the drug the frequency of bullous eruptions and healing process of affected skin areas remained unchanged. This suggests no direct causal relation existing between skin collagenase activity and epidermolysis bullosa. Whether increased collagenase activity reflects a secondary reaction of the organism cannot be concluded from this study.", "contents": "[The effect of collagenase inhibition on bullous eruption and healing process in epidermolysis bullosa]. The collagenase inhibiting effect of erythromycin already observed in vitro was demonstrated also after oral administration of the drug in vivo in one child with epidermolysis bullosa letalis and one child with epidermolysis bullosa dystrophica. Despite inhibition of skin collagenase activity during administration of the drug the frequency of bullous eruptions and healing process of affected skin areas remained unchanged. This suggests no direct causal relation existing between skin collagenase activity and epidermolysis bullosa. Whether increased collagenase activity reflects a secondary reaction of the organism cannot be concluded from this study."}
{"id": "PMID:217852", "title": "Association of osteopetrosis and vitamin D-resistant rickets.", "content": "The following report concerns a case of malignant osteopetrosis associated with hypocalcemic rickets unresponsive to vitamin D. Parathyroid hormone (PTH) and Calcitonin (CT) secretions were studied in basal conditions and under calcium gluconate infusion, before and after high doses of vitamin D. Basal values (PTH: 690 pg Eq/ml; CT: 560 pg/ml) were found to be much higher than in five control subjects of the same age group, even after vitamin D therapy (PTH: 990 pg Eq/ml; CT:450 pg/ml). Like rickets, PTH and CT secretions do not seem, therefore, to be notably influenced by vitamin D therapy.", "contents": "Association of osteopetrosis and vitamin D-resistant rickets. The following report concerns a case of malignant osteopetrosis associated with hypocalcemic rickets unresponsive to vitamin D. Parathyroid hormone (PTH) and Calcitonin (CT) secretions were studied in basal conditions and under calcium gluconate infusion, before and after high doses of vitamin D. Basal values (PTH: 690 pg Eq/ml; CT: 560 pg/ml) were found to be much higher than in five control subjects of the same age group, even after vitamin D therapy (PTH: 990 pg Eq/ml; CT:450 pg/ml). Like rickets, PTH and CT secretions do not seem, therefore, to be notably influenced by vitamin D therapy."}
{"id": "PMID:217853", "title": "Simultaneous occurrence of hypopituitarism and adrenal medullary insufficiency in a boy with hypoglycemia.", "content": "The case of a 6-year-old mentally retarded boy is described, who was delivered by breech presentation and who was later found to have adrenal calcifications. He presented with severe hypoglycemia during infancy and early childhood. Subsequent examinations revealed the coexistence of pituitary growth hormone and ACTH-deficiency and of adrenal medullary insufficiency. The hypothalamus-pituitary-thyroid and -gonadal axes were apparently normal. It is concluded that both, the pituitary and adrenal medullary insufficiency are probably due to the same complications at birth (hypothalamic or pituitary asphyxia and adrenal hemorrhage) and that both conditions contributed to the development of hypoglycemia.", "contents": "Simultaneous occurrence of hypopituitarism and adrenal medullary insufficiency in a boy with hypoglycemia. The case of a 6-year-old mentally retarded boy is described, who was delivered by breech presentation and who was later found to have adrenal calcifications. He presented with severe hypoglycemia during infancy and early childhood. Subsequent examinations revealed the coexistence of pituitary growth hormone and ACTH-deficiency and of adrenal medullary insufficiency. The hypothalamus-pituitary-thyroid and -gonadal axes were apparently normal. It is concluded that both, the pituitary and adrenal medullary insufficiency are probably due to the same complications at birth (hypothalamic or pituitary asphyxia and adrenal hemorrhage) and that both conditions contributed to the development of hypoglycemia."}
{"id": "PMID:217854", "title": "Inhibition of converting enzyme activity by acute hypoxia in dogs.", "content": "We studied the effect of a change in oxygen tension on converting enzyme activity in anesthetized, paralyzed, catheterized dogs ventilated with room air, 100% O2, and hypoxic gas mixtures. Bradykinin was continuously infused into the femoral vein and simultaneous samples drawn from the pulmonary artery and left atrium; bradykinin was extracted into ethanol and measured by radioimmunoassay. Clearance of bradykinin by lung converting enzyme decreased from 96% at PaO2 levels above 95 Torr to 0% below 26 Torr. Inhibition of enzyme activity was rapid in onset (less than 2 min), closely correlated with PaO2 (r = 0.92, P less than 0.001), and reversible within 2 min after return to room air breathing. Converting enzyme activity of the systemic vascular bed was also inhibited by hypoxia; kininase I activity was unaffected by oxygen tension. Although arterial bradykinin concentrations in the range of 0.5 ng/ml produced hypotension in normoxic animals, elevations to 30 ng/ml had no hypotensive effect in hypoxic dogs. During acute hypoxia, venous bradykinin will pass through the lung unmetabolized, and local levels of angiotensin II and bradykinin will vary in vascular beds with different oxygen tensions, providing a finely-graded mechanism for blood flow regulation.", "contents": "Inhibition of converting enzyme activity by acute hypoxia in dogs. We studied the effect of a change in oxygen tension on converting enzyme activity in anesthetized, paralyzed, catheterized dogs ventilated with room air, 100% O2, and hypoxic gas mixtures. Bradykinin was continuously infused into the femoral vein and simultaneous samples drawn from the pulmonary artery and left atrium; bradykinin was extracted into ethanol and measured by radioimmunoassay. Clearance of bradykinin by lung converting enzyme decreased from 96% at PaO2 levels above 95 Torr to 0% below 26 Torr. Inhibition of enzyme activity was rapid in onset (less than 2 min), closely correlated with PaO2 (r = 0.92, P less than 0.001), and reversible within 2 min after return to room air breathing. Converting enzyme activity of the systemic vascular bed was also inhibited by hypoxia; kininase I activity was unaffected by oxygen tension. Although arterial bradykinin concentrations in the range of 0.5 ng/ml produced hypotension in normoxic animals, elevations to 30 ng/ml had no hypotensive effect in hypoxic dogs. During acute hypoxia, venous bradykinin will pass through the lung unmetabolized, and local levels of angiotensin II and bradykinin will vary in vascular beds with different oxygen tensions, providing a finely-graded mechanism for blood flow regulation."}
{"id": "PMID:217855", "title": "Effect of intrapulmonary hematocrit maldistribution on O2, CO2, and inert gas exchange.", "content": "The potential effect of intrapulmonary variations in hematocrit on gas exchange has been studied in theoretical models of the lung containing maldistribution of both hematocrit (Hct) and ventilation-perfusion (VA/Q) ratio. Hematocrit inequality enhanced gas exchange when units of low VA/Q were given a low Hct, arterial PO2 rising by as much as 14 Torr and PCO2 falling by up to 2 Torr depending on the particular distributions of Hct and VA/Q, whereas gas exchange was depressed when units of low VA/Q had a high Hct. After measuring inert gas solubilities in both dog and human blood of different Hct, the effect of Hct inequality on inert gas exchange was similarly assessed. Solubility was found to increase with HCT for less soluble gases. Because of this, conditions for enhancement of inert and O2 exchange by HCt inequality coincided, and it was found that in general the effects on O2 and inert gas transfer were quantitatively internally consistent. Even when Hct inequality was extreme, the resulting perturbation of inert gas concentrations was sufficiently small that the main features of the recovered VA/Q distributions were unaltered.", "contents": "Effect of intrapulmonary hematocrit maldistribution on O2, CO2, and inert gas exchange. The potential effect of intrapulmonary variations in hematocrit on gas exchange has been studied in theoretical models of the lung containing maldistribution of both hematocrit (Hct) and ventilation-perfusion (VA/Q) ratio. Hematocrit inequality enhanced gas exchange when units of low VA/Q were given a low Hct, arterial PO2 rising by as much as 14 Torr and PCO2 falling by up to 2 Torr depending on the particular distributions of Hct and VA/Q, whereas gas exchange was depressed when units of low VA/Q had a high Hct. After measuring inert gas solubilities in both dog and human blood of different Hct, the effect of Hct inequality on inert gas exchange was similarly assessed. Solubility was found to increase with HCT for less soluble gases. Because of this, conditions for enhancement of inert and O2 exchange by HCt inequality coincided, and it was found that in general the effects on O2 and inert gas transfer were quantitatively internally consistent. Even when Hct inequality was extreme, the resulting perturbation of inert gas concentrations was sufficiently small that the main features of the recovered VA/Q distributions were unaltered."}
{"id": "PMID:217856", "title": "Susceptibility of different gases to ventilation-perfusion inequality.", "content": "Calculations of O2 and CO2 transfer in lung models of both series and parallel ventilation-perfusion (VA/Q) inequality have been performed by several investigators. In some cases, O2 uptake was found to be depressed more than CO2 output but in other examples CO2 elimination was interfered with to a greater extent. To understand the fundamental basis of differential susceptibility of various gases to VA/Q inequality, an algebraic analysis of inert gas exchange in two-compartment models of both series and parallel inequality is presented. For both types of inequality, the result is remarkably simple, in that the gas most affected is one whose partition coefficient is the geometric mean of the ventilation-to-perfusion ratios of the two compartments. Transfer of O2 and CO2 in these models was predicted well by the inert gas results not only qualitatively but even quantitatively. Similarly good quantitative predictions were obtained in more complicated multicompartment VA/Q distributions. The results therefore explain and reconcile the findings of various reported studies and in particular account for the observation that CO2 transfer is compromised in many examples of series inequality.", "contents": "Susceptibility of different gases to ventilation-perfusion inequality. Calculations of O2 and CO2 transfer in lung models of both series and parallel ventilation-perfusion (VA/Q) inequality have been performed by several investigators. In some cases, O2 uptake was found to be depressed more than CO2 output but in other examples CO2 elimination was interfered with to a greater extent. To understand the fundamental basis of differential susceptibility of various gases to VA/Q inequality, an algebraic analysis of inert gas exchange in two-compartment models of both series and parallel inequality is presented. For both types of inequality, the result is remarkably simple, in that the gas most affected is one whose partition coefficient is the geometric mean of the ventilation-to-perfusion ratios of the two compartments. Transfer of O2 and CO2 in these models was predicted well by the inert gas results not only qualitatively but even quantitatively. Similarly good quantitative predictions were obtained in more complicated multicompartment VA/Q distributions. The results therefore explain and reconcile the findings of various reported studies and in particular account for the observation that CO2 transfer is compromised in many examples of series inequality."}
{"id": "PMID:217858", "title": "Rotaviral diarrhea in pigs: brief review.", "content": "Rotavirus is a name given to a group of viruses that have similar characteristics and are generally capable of causing diarrhea in the young. Infection of pigs with porcine rotavirus is common and widespread and can result in diarrhea, especially in 1- to 4-week-old pigs. This virus is frequently associated with a diarrheal syndrome popularity known as \"white scours,\" \"milk scours,\" or \"3-week-old scours.\" Pigs less than 1 week old are infrequently infected, presumably because of adequate passive immunity. The infection resembles enzootic transmissible gastroenteritis. Diagnosis can be made by immunofluorescent staining of mucosal scrappings from the small intestines.", "contents": "Rotaviral diarrhea in pigs: brief review. Rotavirus is a name given to a group of viruses that have similar characteristics and are generally capable of causing diarrhea in the young. Infection of pigs with porcine rotavirus is common and widespread and can result in diarrhea, especially in 1- to 4-week-old pigs. This virus is frequently associated with a diarrheal syndrome popularity known as \"white scours,\" \"milk scours,\" or \"3-week-old scours.\" Pigs less than 1 week old are infrequently infected, presumably because of adequate passive immunity. The infection resembles enzootic transmissible gastroenteritis. Diagnosis can be made by immunofluorescent staining of mucosal scrappings from the small intestines."}
{"id": "PMID:217859", "title": "The structure and ultrastructure of the renal tubule of the urodele amphibian, Amphiuma means.", "content": "The renal corpuscle and segments of the renal tubule of the urodele amphibian Amphiuma means have been described and studied by light and electron microscopy as a background for investigations on the effects of hormones, drugs, toxins and carcinogens on cell structure and function in long-term organ cultures of kidney explants. Notable features of the A. means kidney include the number and variety of cytoplasmic inclusions in the cells of the proximal segment, the comparatively thick glomerular filter, and the presence of possible renin granules in the endothelial cells lining the afferent arteriole near its point of entry to the glomerular capsule.", "contents": "The structure and ultrastructure of the renal tubule of the urodele amphibian, Amphiuma means. The renal corpuscle and segments of the renal tubule of the urodele amphibian Amphiuma means have been described and studied by light and electron microscopy as a background for investigations on the effects of hormones, drugs, toxins and carcinogens on cell structure and function in long-term organ cultures of kidney explants. Notable features of the A. means kidney include the number and variety of cytoplasmic inclusions in the cells of the proximal segment, the comparatively thick glomerular filter, and the presence of possible renin granules in the endothelial cells lining the afferent arteriole near its point of entry to the glomerular capsule."}
{"id": "PMID:217860", "title": "Analysis of fat-soluble vitamins. XXI. High pressure liquid chromatographic assay methods for vitamin D in vitamin D concentrates.", "content": "Two high pressure liquid chromatographic methods, a straight and a reverse phase system, were developed and compared with the official (chemical) AOAC method for vitamin D concentrates. The effects of the systematic error and the reproducibility of using an internal or external standard were studied, as well as the effect of using peak height or peak height X retention time for calculating the potential vitamin D content. A method is given for determining the conversion factor to calculate previtamin D as vitamin D. Based on the results of the comparison, the following conditions were selected for collaborative study: straight phase, amyl alcohol-hexane mobile phase, external standard, and calculation of potency by peak height.", "contents": "Analysis of fat-soluble vitamins. XXI. High pressure liquid chromatographic assay methods for vitamin D in vitamin D concentrates. Two high pressure liquid chromatographic methods, a straight and a reverse phase system, were developed and compared with the official (chemical) AOAC method for vitamin D concentrates. The effects of the systematic error and the reproducibility of using an internal or external standard were studied, as well as the effect of using peak height or peak height X retention time for calculating the potential vitamin D content. A method is given for determining the conversion factor to calculate previtamin D as vitamin D. Based on the results of the comparison, the following conditions were selected for collaborative study: straight phase, amyl alcohol-hexane mobile phase, external standard, and calculation of potency by peak height."}
{"id": "PMID:217862", "title": "\"Self-catabolite repression\" of pectate lyase in Erwinia carotovora.", "content": "The induction of pectate lyase of Erwinia carotovora was repressed by a high concentration of its inducer. The concomitant addition of cyclic adenosine 3',5'-monophosphate reversed this repression.", "contents": "\"Self-catabolite repression\" of pectate lyase in Erwinia carotovora. The induction of pectate lyase of Erwinia carotovora was repressed by a high concentration of its inducer. The concomitant addition of cyclic adenosine 3',5'-monophosphate reversed this repression."}
{"id": "PMID:217863", "title": "Transport of alpha-p-nitrophenylgalactoside by the lactose carrier of Escherichia coli.", "content": "alpha-p-Nitrophenylgalactoside was found to be accumulated by the lactose transport-system of Escherichia coli. This fact may help to resolve the differences in the reported number of sugar binding sites of the lactose transport protein in nonenergized and energized membrane vesicles.", "contents": "Transport of alpha-p-nitrophenylgalactoside by the lactose carrier of Escherichia coli. alpha-p-Nitrophenylgalactoside was found to be accumulated by the lactose transport-system of Escherichia coli. This fact may help to resolve the differences in the reported number of sugar binding sites of the lactose transport protein in nonenergized and energized membrane vesicles."}
{"id": "PMID:217864", "title": "Lipid and lipopolysaccharide composition of Escherichia coli surface-altered mutants selected for resistance to levallorphan, tetracaine, and polymyxin.", "content": "Certain mutants of Escherichia coli with an altered permeability barrier have an essentially normal lipopolysaccharide, fatty acid, and phospholipid content, with a slight increase in the membrane protein:lipid ratio. The phospholipid metabolism of the lev and tec strains shows an abnormal response to growth in the selective agents levallorphan and tetracaine, respectively.", "contents": "Lipid and lipopolysaccharide composition of Escherichia coli surface-altered mutants selected for resistance to levallorphan, tetracaine, and polymyxin. Certain mutants of Escherichia coli with an altered permeability barrier have an essentially normal lipopolysaccharide, fatty acid, and phospholipid content, with a slight increase in the membrane protein:lipid ratio. The phospholipid metabolism of the lev and tec strains shows an abnormal response to growth in the selective agents levallorphan and tetracaine, respectively."}
{"id": "PMID:217865", "title": "Purification and properties of acetate kinase from Acholeplasma laidlawii.", "content": "Acetate kinase (EC 2.7.2.1) was purified from Acholeplasma laidlawii cytoplasm by a combination of ammonium sulfate fractionation, gel filtration, diethylaminoethyl-cellulose chromatography, and affinity chromatography on 8-(6-aminohexylamino)-adenosine 5'-triphosphate conjugated to Sepharose 4B. The enzyme was composed of polypeptide chains of about 50,000 molecular weight as estimated from sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Under nondenaturating conditions, apparent molecular weights between 64,000 and 130,000 were obtained, depending upon mainly the ionic strength of the test solution. The enzyme had a narrow specificity for phosphate acceptor acids, whereas both purine and pyrimidine nucleoside triphosphates were suitable phosphate donors. Na(+) and K(+) inhibited both acetyl phosphate and adenosine 5'-triphosphate synthesis, and the latter was also inhibited by high concentrations of adenosine 5'-diphosphate and acetyl phosphate. This substrate inhibition was partially abolished by 0.5 M NaCl. The enzyme catalyzed the independent adenosine 5'-diphosphate<-->adenosine 5'-triphosphate and acetate<-->acetyl phosphate exchanges. The rate of the latter was enhanced by the addition of cosubstrate Mg(2+)-adenosine 5'-triphosphate. The high affinity for substrates, except for acetate, indicated that under physiological conditions the direction of the enzymic reaction favors adenosine 5'-triphosphate synthesis. Thus, a mechanism for adenosine 5'-triphosphate generation in mycoplasmas is suggested.", "contents": "Purification and properties of acetate kinase from Acholeplasma laidlawii. Acetate kinase (EC 2.7.2.1) was purified from Acholeplasma laidlawii cytoplasm by a combination of ammonium sulfate fractionation, gel filtration, diethylaminoethyl-cellulose chromatography, and affinity chromatography on 8-(6-aminohexylamino)-adenosine 5'-triphosphate conjugated to Sepharose 4B. The enzyme was composed of polypeptide chains of about 50,000 molecular weight as estimated from sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Under nondenaturating conditions, apparent molecular weights between 64,000 and 130,000 were obtained, depending upon mainly the ionic strength of the test solution. The enzyme had a narrow specificity for phosphate acceptor acids, whereas both purine and pyrimidine nucleoside triphosphates were suitable phosphate donors. Na(+) and K(+) inhibited both acetyl phosphate and adenosine 5'-triphosphate synthesis, and the latter was also inhibited by high concentrations of adenosine 5'-diphosphate and acetyl phosphate. This substrate inhibition was partially abolished by 0.5 M NaCl. The enzyme catalyzed the independent adenosine 5'-diphosphate<-->adenosine 5'-triphosphate and acetate<-->acetyl phosphate exchanges. The rate of the latter was enhanced by the addition of cosubstrate Mg(2+)-adenosine 5'-triphosphate. The high affinity for substrates, except for acetate, indicated that under physiological conditions the direction of the enzymic reaction favors adenosine 5'-triphosphate synthesis. Thus, a mechanism for adenosine 5'-triphosphate generation in mycoplasmas is suggested."}
{"id": "PMID:217866", "title": "High and selective resistance to mecillinam in adenylate cyclase-deficient or cyclic adenosine 3',5'-monophosphate receptor protein-deficient mutants of Escherichia coli.", "content": "Adenylate cyclase-deficient (cya) mutants of Escherichia coli K-12 were selectively and highly resistant to mecillinam (FL1060) among several beta-lactam antibiotics in the absence of cyclic adenosine 3',5'-monophosphate (cAMP). They became sensitive to the drug in the presence of cAMP. Also, cAMP receptor protein-negative (crp) mutants, with the exception of strain 5333, were highly resistant to mecillinam in the presence and in the absence of cAMP. Mecillinam exerted two distinct and sequential effects in both cya+ strains and cya strains supplemented with cAMP: (i) rounding of cells and (ii) cessation of cell division. The first effect was accompanied by a decrease in growth rate, whereas the second effect was accompanied by enlargement and lysis of the rounded cells. The second effect of mecillinam was dependent on inoculum size and cAMP. When the cell density was above about 10(6) cells per ml, the rounded cells stopped dividing but did not lyse. In the absence of cAMP, cya strains neither stopped dividing nor lysed; they were resistant to the second, lethal effect of mecillinam.", "contents": "High and selective resistance to mecillinam in adenylate cyclase-deficient or cyclic adenosine 3',5'-monophosphate receptor protein-deficient mutants of Escherichia coli. Adenylate cyclase-deficient (cya) mutants of Escherichia coli K-12 were selectively and highly resistant to mecillinam (FL1060) among several beta-lactam antibiotics in the absence of cyclic adenosine 3',5'-monophosphate (cAMP). They became sensitive to the drug in the presence of cAMP. Also, cAMP receptor protein-negative (crp) mutants, with the exception of strain 5333, were highly resistant to mecillinam in the presence and in the absence of cAMP. Mecillinam exerted two distinct and sequential effects in both cya+ strains and cya strains supplemented with cAMP: (i) rounding of cells and (ii) cessation of cell division. The first effect was accompanied by a decrease in growth rate, whereas the second effect was accompanied by enlargement and lysis of the rounded cells. The second effect of mecillinam was dependent on inoculum size and cAMP. When the cell density was above about 10(6) cells per ml, the rounded cells stopped dividing but did not lyse. In the absence of cAMP, cya strains neither stopped dividing nor lysed; they were resistant to the second, lethal effect of mecillinam."}
{"id": "PMID:217867", "title": "Diglyceride kinase mutants of Escherichia coli: inner membrane association of 1,2-diglyceride and its relation to synthesis of membrane-derived oligosaccharides.", "content": "Mutants of Escherichia coli defective in diglyceride kinase contain 10 to 20 times more sn-1,2-diglyceride than normal cells. This material constitutes about 8% of the total lipid in such strains. We now report that this excess diglyceride is recovered in the particulate fraction, primarily in association with the inner, cytoplasmic membrane. The diglyceride kinase of wild-type cells was recovered in the same inner membrane fractions. The conditions employed for the preparation of the membranes did not appear to cause significant redistribution of lipids and proteins. The biochemical reactions leading to the formation of diglyceride in E. coli are not known. To determine whether diglyceride formation requires concurrent synthesis of the membrane-derived oligosaccharides (H. Schulman and E. P. Kennedy, J. Biol. Chem. 252:4250-4255, 1977), we have constructed a double mutant defective in both the kinase (dgk) and phosphoglucose isomerase (pgi). When oligosaccharide synthesis was inhibited in this organism by growing the cells on amino acids as the sole carbon source, the diglyceride was no longer present in large amounts. When glucose was also added to the medium, the pgi mutation was bypassed, oligosaccharide synthesis resumed, and diglyceride again accumulated. These findings suggest that diglyceride may arise during the transfer of the sn-glycero-1-P moiety from phosphatidylglycerol (and possibly cardiolipin) to the oligosaccharides. In wild-type cells the kinase permits the cyclical reutilization of diglyceride molecules for phospholipid biosynthesis.", "contents": "Diglyceride kinase mutants of Escherichia coli: inner membrane association of 1,2-diglyceride and its relation to synthesis of membrane-derived oligosaccharides. Mutants of Escherichia coli defective in diglyceride kinase contain 10 to 20 times more sn-1,2-diglyceride than normal cells. This material constitutes about 8% of the total lipid in such strains. We now report that this excess diglyceride is recovered in the particulate fraction, primarily in association with the inner, cytoplasmic membrane. The diglyceride kinase of wild-type cells was recovered in the same inner membrane fractions. The conditions employed for the preparation of the membranes did not appear to cause significant redistribution of lipids and proteins. The biochemical reactions leading to the formation of diglyceride in E. coli are not known. To determine whether diglyceride formation requires concurrent synthesis of the membrane-derived oligosaccharides (H. Schulman and E. P. Kennedy, J. Biol. Chem. 252:4250-4255, 1977), we have constructed a double mutant defective in both the kinase (dgk) and phosphoglucose isomerase (pgi). When oligosaccharide synthesis was inhibited in this organism by growing the cells on amino acids as the sole carbon source, the diglyceride was no longer present in large amounts. When glucose was also added to the medium, the pgi mutation was bypassed, oligosaccharide synthesis resumed, and diglyceride again accumulated. These findings suggest that diglyceride may arise during the transfer of the sn-glycero-1-P moiety from phosphatidylglycerol (and possibly cardiolipin) to the oligosaccharides. In wild-type cells the kinase permits the cyclical reutilization of diglyceride molecules for phospholipid biosynthesis."}
{"id": "PMID:217868", "title": "The use of multivariate personality strategies in predicting attrition from alcoholism treatment.", "content": "This study attempted to replicate previous work which used discriminant analysis to predict attrition from an outpatient alcoholism treatment program. The MMPI-168 and Rotter's locus of control scale were administered to a sample of inpatient male alcoholics who later entered outpatient treatment. The MMPI-168 was scored using 5 factor-analytically derived measures, Depression, Somatization, Low Morale, Psychotic Distortion and Acting Out. Both studies found Depression to be the strongest predictor of attrition after controlling for Somatization. Internal locus of control was also related to attrition. The utility of discriminant analysis in predicting outcome from personality data and the ramifications for treatment is discussed.", "contents": "The use of multivariate personality strategies in predicting attrition from alcoholism treatment. This study attempted to replicate previous work which used discriminant analysis to predict attrition from an outpatient alcoholism treatment program. The MMPI-168 and Rotter's locus of control scale were administered to a sample of inpatient male alcoholics who later entered outpatient treatment. The MMPI-168 was scored using 5 factor-analytically derived measures, Depression, Somatization, Low Morale, Psychotic Distortion and Acting Out. Both studies found Depression to be the strongest predictor of attrition after controlling for Somatization. Internal locus of control was also related to attrition. The utility of discriminant analysis in predicting outcome from personality data and the ramifications for treatment is discussed."}
{"id": "PMID:217869", "title": "Interaction of iodinated human [D-Ala2]beta-endorphin with opitate receptors.", "content": "The interaction of beta-endorphin with opiate receptors was studied by using the radioiodinated, metabolically stable D-Ala2 derivative of human beta-endorphin. This analog binds specifically to rat brain membrane preparations with an apparent Kd of about 2.5 x 10-9 M. The ability of various enkephalin analogs, as well as opiate agonists and antagonists, to inhibit the binding of beta-endorphin clearly demonstrates that this peptide can bind to opiate receptors. However, the effects of various cations on the binding of 125I-[D-Ala2]beta-endorphin are markedly different from those found for enkephalin binding. Sodium ion at physiological concentrations decreases substantially the binding of enkephalins but only slightly decreases endorphin binding, whereas manganese enhances enkephalin binding but has no effect on endorphin binding. Moreover, potassium (100 mM) decreases the binding of beta-endorphin but does not affect enkephalin binding. These results suggest that beta-endorphin and enkephalin bind differently to the same receptor or bind to different receptors with overlapping specificity.", "contents": "Interaction of iodinated human [D-Ala2]beta-endorphin with opitate receptors. The interaction of beta-endorphin with opiate receptors was studied by using the radioiodinated, metabolically stable D-Ala2 derivative of human beta-endorphin. This analog binds specifically to rat brain membrane preparations with an apparent Kd of about 2.5 x 10-9 M. The ability of various enkephalin analogs, as well as opiate agonists and antagonists, to inhibit the binding of beta-endorphin clearly demonstrates that this peptide can bind to opiate receptors. However, the effects of various cations on the binding of 125I-[D-Ala2]beta-endorphin are markedly different from those found for enkephalin binding. Sodium ion at physiological concentrations decreases substantially the binding of enkephalins but only slightly decreases endorphin binding, whereas manganese enhances enkephalin binding but has no effect on endorphin binding. Moreover, potassium (100 mM) decreases the binding of beta-endorphin but does not affect enkephalin binding. These results suggest that beta-endorphin and enkephalin bind differently to the same receptor or bind to different receptors with overlapping specificity."}
{"id": "PMID:217870", "title": "The fate of cytoplasmic vanadium. Implications on (NA,K)-ATPase inhibition.", "content": "The fate of vanadate (+5 oxidation state of vanadium) taken up by the red cell was studied using EPR spectroscopy. The appearance of an EPR signal indicated that most of the cytoplasmic vanadate is reduced to the +4 oxidation state with axial symmetry characteristic of vanadyl ions. The signal at 23 degrees C was characteristic of an immobilized system indicating that the vanadyl ions in the cytoplasm are associated with a large molecule. [48V]Vanadium eluted with hemoglobin when the lysate from Na3[48V[O4-treated red cells was passed through a Sephadex G-100 column and rabbit anti-human hemoglobin serum caused a hemoglobin-specific precipitation of 48V when added to the red cell lysate. Both results indicate that hemoglobin is the protein which binds cytoplasmic vanadyl ions. However, neither sodium vanadate nor vanadyl sulfate bound to purified hemoglobin in vitro. Finally, transient kinetics of vanadyl sulfate interaction with the sodium-and potassium-stimulated adenosine triphosphatase showed that the +4 oxidation state of vanadium is less effective than the +5 oxidation state in inhibiting this enzyme. These results indicate that oxidation-reduction reactions in the cytoplasm are capable of relieving vanadate inhibition of cation transport.", "contents": "The fate of cytoplasmic vanadium. Implications on (NA,K)-ATPase inhibition. The fate of vanadate (+5 oxidation state of vanadium) taken up by the red cell was studied using EPR spectroscopy. The appearance of an EPR signal indicated that most of the cytoplasmic vanadate is reduced to the +4 oxidation state with axial symmetry characteristic of vanadyl ions. The signal at 23 degrees C was characteristic of an immobilized system indicating that the vanadyl ions in the cytoplasm are associated with a large molecule. [48V]Vanadium eluted with hemoglobin when the lysate from Na3[48V[O4-treated red cells was passed through a Sephadex G-100 column and rabbit anti-human hemoglobin serum caused a hemoglobin-specific precipitation of 48V when added to the red cell lysate. Both results indicate that hemoglobin is the protein which binds cytoplasmic vanadyl ions. However, neither sodium vanadate nor vanadyl sulfate bound to purified hemoglobin in vitro. Finally, transient kinetics of vanadyl sulfate interaction with the sodium-and potassium-stimulated adenosine triphosphatase showed that the +4 oxidation state of vanadium is less effective than the +5 oxidation state in inhibiting this enzyme. These results indicate that oxidation-reduction reactions in the cytoplasm are capable of relieving vanadate inhibition of cation transport."}
{"id": "PMID:217871", "title": "The hydrolysis of cholesterol esters in plasma lipoproteins by hormone-sensitive cholesterol esterase from adipose tissue.", "content": "Adipose tissue contains a high level of neutral esterase active against emulsions of cholesteryl oleate. The present studies show that this enzyme can also effectively hydrolyze the cholesterol esters in native rat plasma high density lipoproteins (HDL) and low density lipoproteins (LDL). The hydrolysis of lipoprotein cholesterol esters by a pH 5.2 isoelectric precipitate fraction from the freshly prepared 100,000 X g supernatant of chicken adipose tissue was low, but increased more than 50-fold on activation with cyclic AMP-dependent protein kinase. Rat adipose tissue homogenates were also very active against lipoprotein cholesterol esters, hydrolyzing as much as 60% of the total labeled cholesterol ester in HDL or LDL in 1 h. Activity was optimal at pH 7 and very low at pH 4. No protease activity was detected at pH 7 and, since assays were done in 2 mM EDTA, phospholipase A activity was presumably negligible. The results show that hormone-sensitive cholesterol esterase of adipose tissue has ready access to the neutral lipid core of plasma lipoproteins, either because the enzyme penetrates the polar shell or because the cholesterol ester in the core is exposed, at least intermittently, to allow enzyme-substrate complex formation. Whether or not this enzyme activity plays a role in lipoprotein degradation by adipose tissue remains to be determined.", "contents": "The hydrolysis of cholesterol esters in plasma lipoproteins by hormone-sensitive cholesterol esterase from adipose tissue. Adipose tissue contains a high level of neutral esterase active against emulsions of cholesteryl oleate. The present studies show that this enzyme can also effectively hydrolyze the cholesterol esters in native rat plasma high density lipoproteins (HDL) and low density lipoproteins (LDL). The hydrolysis of lipoprotein cholesterol esters by a pH 5.2 isoelectric precipitate fraction from the freshly prepared 100,000 X g supernatant of chicken adipose tissue was low, but increased more than 50-fold on activation with cyclic AMP-dependent protein kinase. Rat adipose tissue homogenates were also very active against lipoprotein cholesterol esters, hydrolyzing as much as 60% of the total labeled cholesterol ester in HDL or LDL in 1 h. Activity was optimal at pH 7 and very low at pH 4. No protease activity was detected at pH 7 and, since assays were done in 2 mM EDTA, phospholipase A activity was presumably negligible. The results show that hormone-sensitive cholesterol esterase of adipose tissue has ready access to the neutral lipid core of plasma lipoproteins, either because the enzyme penetrates the polar shell or because the cholesterol ester in the core is exposed, at least intermittently, to allow enzyme-substrate complex formation. Whether or not this enzyme activity plays a role in lipoprotein degradation by adipose tissue remains to be determined."}
{"id": "PMID:217872", "title": "Succinic semialdehyde dehydrogenase. Reactivity of lysyl residues.", "content": "The enzyme succinic semialdehyde dehydrogenase from pig brain has been 2000-fold purified by a combination of DEAE-cellulose, hydroxyapatite, and AMP-Sepharose chromatography. This preparation has a molecular weight of 160,000 and a specific activity of 5.3 mumol/min.mg at 25 degrees C. The inhibition of succinic semialdehyde dehydrogenase by carbonyl compounds, i.e. P-pyridoxal and o-phthalaldehyde was investigated in detail. The enzyme is reversible, inhibited by preincubation with P-pyridoxal (mixing molar ratio, 300:1) at either 25 degrees or 37 degrees C. Reduction with NaBH1 results in the incorporation of approximately 4 mol of P-pyridoxyl residues/mol of enzyme. NAD+ protects the enzyme against inactivation by P-pyridoxal, whereas the substrate succinic semialdehyde failed to prevent the reaction of P-pyridoxal with lysine residues of the protein. The binding of approximately 10 mol of o-phthalaldehyde/mol of enzyme results in irreversible loss of catalytic activity. The reaction is fast and easily monitored by absorption and fluorescence spectroscopy.", "contents": "Succinic semialdehyde dehydrogenase. Reactivity of lysyl residues. The enzyme succinic semialdehyde dehydrogenase from pig brain has been 2000-fold purified by a combination of DEAE-cellulose, hydroxyapatite, and AMP-Sepharose chromatography. This preparation has a molecular weight of 160,000 and a specific activity of 5.3 mumol/min.mg at 25 degrees C. The inhibition of succinic semialdehyde dehydrogenase by carbonyl compounds, i.e. P-pyridoxal and o-phthalaldehyde was investigated in detail. The enzyme is reversible, inhibited by preincubation with P-pyridoxal (mixing molar ratio, 300:1) at either 25 degrees or 37 degrees C. Reduction with NaBH1 results in the incorporation of approximately 4 mol of P-pyridoxyl residues/mol of enzyme. NAD+ protects the enzyme against inactivation by P-pyridoxal, whereas the substrate succinic semialdehyde failed to prevent the reaction of P-pyridoxal with lysine residues of the protein. The binding of approximately 10 mol of o-phthalaldehyde/mol of enzyme results in irreversible loss of catalytic activity. The reaction is fast and easily monitored by absorption and fluorescence spectroscopy."}
{"id": "PMID:217877", "title": "Initiation of RNA synthesis in vitro by vesicular stomatitis virus. Role of ATP.", "content": "The ATP requirement during RNA transcription by the RNA-dependent RNA polymerase associated with purified vesicular stomatitis virus was studied during chain initiation and chain elongation steps. Initiation of transcription in vitro has an apparent Km for ATP of approximately 500 micron, whereas the apparent Km for ATP during chain elongation is almost identical with those for the other three ribonucleoside triphosphates, i.e. 20 to 30 micron. Further analysis of the transcription process demonstrated that the beta-gamma imido analogue of ATP cannot be used for the initiation step. However, it can be incorporated into RNA during chain elongation. These results indicate that a hydrolyzable form of the beta-gamma phosphodiester bond in ATP is required for the initiation process and also support the hypothesis for a single promoter site for the initiation of transcription on the genome of vesicular stomatitis virus.", "contents": "Initiation of RNA synthesis in vitro by vesicular stomatitis virus. Role of ATP. The ATP requirement during RNA transcription by the RNA-dependent RNA polymerase associated with purified vesicular stomatitis virus was studied during chain initiation and chain elongation steps. Initiation of transcription in vitro has an apparent Km for ATP of approximately 500 micron, whereas the apparent Km for ATP during chain elongation is almost identical with those for the other three ribonucleoside triphosphates, i.e. 20 to 30 micron. Further analysis of the transcription process demonstrated that the beta-gamma imido analogue of ATP cannot be used for the initiation step. However, it can be incorporated into RNA during chain elongation. These results indicate that a hydrolyzable form of the beta-gamma phosphodiester bond in ATP is required for the initiation process and also support the hypothesis for a single promoter site for the initiation of transcription on the genome of vesicular stomatitis virus."}
{"id": "PMID:217880", "title": "Reconstitution of lipid vesicles associated with HVJ (Sendai virus) sikes. Purification and some properties of vesicles containing nontoxic fragment A of diphtheria toxin.", "content": "A mixture of HVJ (Sendai virus) spike proteins, the nontoxic fragment A of diphtheria toxin, lecithin, and cholesterol was solubilized in sucrose solution containing a nonionic neutral detergent. The liposomal vesicles which formed on removal of the detergent by dialysis were purified by gel filtration and centrifugation on a sucrose gradient. The resulting purified vesicles had hemagglutinating activity, hemolytic activity and, after solubilization, the enzymic activity of fragment A. The vesicles had no cell fusion activity. Electron microscopy showed that both the outside and inside of membranes of the vesicles were associated with the spikes. When the vesicles were freeze-fractured, no large aggregates of particles were seen on either face. Such fragment A-containing lipid vesicles (liposomes) with HVJ spikes bound to mamalian cell membrane and released their fragment A into the cytoplasm causing cell death. Neither fragment A-containing liposomes without spikes nor empty liposomes with spikes were toxic.", "contents": "Reconstitution of lipid vesicles associated with HVJ (Sendai virus) sikes. Purification and some properties of vesicles containing nontoxic fragment A of diphtheria toxin. A mixture of HVJ (Sendai virus) spike proteins, the nontoxic fragment A of diphtheria toxin, lecithin, and cholesterol was solubilized in sucrose solution containing a nonionic neutral detergent. The liposomal vesicles which formed on removal of the detergent by dialysis were purified by gel filtration and centrifugation on a sucrose gradient. The resulting purified vesicles had hemagglutinating activity, hemolytic activity and, after solubilization, the enzymic activity of fragment A. The vesicles had no cell fusion activity. Electron microscopy showed that both the outside and inside of membranes of the vesicles were associated with the spikes. When the vesicles were freeze-fractured, no large aggregates of particles were seen on either face. Such fragment A-containing lipid vesicles (liposomes) with HVJ spikes bound to mamalian cell membrane and released their fragment A into the cytoplasm causing cell death. Neither fragment A-containing liposomes without spikes nor empty liposomes with spikes were toxic."}
{"id": "PMID:217881", "title": "Hormonally induced cell shape changes in cultured rat ovarian granulosa cells.", "content": "Cultured rat ovarian granulosa cells undergo a dramatic morphological change when exposed to follicle-stimulating hormone (FSH). Exposure to FSH causes the flattened epithelioid granulosa cells to assume a nearly spherical shape while retaining cytoplasmic processes which contact the substrate as well as adjacent cells. This effect of FSH is preceded by a dose-dependent increase in intracellular cAMP, is potentiated by cyclic nucleotide phosphodiesterase inhibitors, and is mimicked by dibutyryl cAMP. Prostaglandins E1 or E2 and cholera enterotoxin also cause the cells to change shape. A subpopulation of the cells responds to luteinizing hormone. These morphological changes, which are blocked by 2,4-dinitrophenol, resemble those produced by treating cultures with cytochalasin B. Electron microscopy shows that the unstimulated, flattened cells contain bundles of microfilaments particularly in the cortical and basal regions. After FSH stimulation, microfilament bundles are not found in the rounded granulosa cell bodies but they are present in the thin cytoplasmic processes. These data suggest that the morphological change results from a cAMP-mediated, energy-dependent mechanism that may involve the alteration of microfilaments in these cells.", "contents": "Hormonally induced cell shape changes in cultured rat ovarian granulosa cells. Cultured rat ovarian granulosa cells undergo a dramatic morphological change when exposed to follicle-stimulating hormone (FSH). Exposure to FSH causes the flattened epithelioid granulosa cells to assume a nearly spherical shape while retaining cytoplasmic processes which contact the substrate as well as adjacent cells. This effect of FSH is preceded by a dose-dependent increase in intracellular cAMP, is potentiated by cyclic nucleotide phosphodiesterase inhibitors, and is mimicked by dibutyryl cAMP. Prostaglandins E1 or E2 and cholera enterotoxin also cause the cells to change shape. A subpopulation of the cells responds to luteinizing hormone. These morphological changes, which are blocked by 2,4-dinitrophenol, resemble those produced by treating cultures with cytochalasin B. Electron microscopy shows that the unstimulated, flattened cells contain bundles of microfilaments particularly in the cortical and basal regions. After FSH stimulation, microfilament bundles are not found in the rounded granulosa cell bodies but they are present in the thin cytoplasmic processes. These data suggest that the morphological change results from a cAMP-mediated, energy-dependent mechanism that may involve the alteration of microfilaments in these cells."}
{"id": "PMID:217882", "title": "Calcium-binding modulator protein from the unfertilized egg of the sea urchin Arbacia punctulata.", "content": "We have purified and partly characterized a calcium-binding protein from the unfertilized egg of the sea urchin Arbacia punctulata. This protein closely resembles the calcium-binding modulator protein of bovine brain in its molecular weight, electrophoretic mobility, amino acid analysis, and peptide map. It activates bovine brain phosphodiesterase in the presence of calcium but has no effect on the phosphodiesterase of the Arbacia egg. Densitometric scanning of acrylamide gels of arbacia egg homogenates shows the modulator protein to represent 0.1% of the total protein of the egg. At 10(-4) M free calcium, the protein binds four calcium ions per 17,000-dalton molecule. We have used a column of rabbit skeletal muscle troponin-I covalently coupled to Sepharose 4B as an affinity column to selectively purify the Arbacia egg calcium-binding protein. This column has also been used to purify bovine brain modulator protein and may prove of general use in isolating similar proteins from other sources. The technique may be particularly helpful when only small quantities of starting material are available.", "contents": "Calcium-binding modulator protein from the unfertilized egg of the sea urchin Arbacia punctulata. We have purified and partly characterized a calcium-binding protein from the unfertilized egg of the sea urchin Arbacia punctulata. This protein closely resembles the calcium-binding modulator protein of bovine brain in its molecular weight, electrophoretic mobility, amino acid analysis, and peptide map. It activates bovine brain phosphodiesterase in the presence of calcium but has no effect on the phosphodiesterase of the Arbacia egg. Densitometric scanning of acrylamide gels of arbacia egg homogenates shows the modulator protein to represent 0.1% of the total protein of the egg. At 10(-4) M free calcium, the protein binds four calcium ions per 17,000-dalton molecule. We have used a column of rabbit skeletal muscle troponin-I covalently coupled to Sepharose 4B as an affinity column to selectively purify the Arbacia egg calcium-binding protein. This column has also been used to purify bovine brain modulator protein and may prove of general use in isolating similar proteins from other sources. The technique may be particularly helpful when only small quantities of starting material are available."}
{"id": "PMID:217883", "title": "Lipid-saccharide intermediates and glycoprotein biosynthesis in a temperature-sensitive Chinese hamster cell mutant.", "content": "The characterization of a temperature-sensitive Chinese hamster cell mutant has been continued with the aim of localizing the apparent defect in glycoprotein synthesis (Tenner et al., '77). Although the mutation is lethal, a demonstration of the ability of the mutant cells to support proliferation of Mengo virus at the nonpermissive temperature indicates that the general metabolic processes of the cells remain intact at a time when glycoprotein synthesis is severely depressed. A quantitative study of protein synthesis on membrane-associated polysomes suggests that the synthesis of the polypeptide portion of the glycoproteins at 40.8 degrees C may be normal. The investigation of lipid-saccharide molecules which have been implicated in the formation and transfer of the oligosaccharide \"core\" to polypeptide acceptors shows that mutant cells at the nonpermissive temperature are capable of synthesizing these lipid saccharides normally, and that the pool of the dolichyl oligosaccharides is maintained at a constant level independent of the temperature. The rate of formation of the lipid-oligosaccharide, however, is reduced in intact mutant cells at the nonpermissive temperature. Further investigations show this decreased rate to be the result of an increased half life of the lipid-oligosaccharide at 40.8 degrees C. These data indicate that the temperature-sensitive step in glycoprotein biosynthesis is the transfer of the oligosaccharide core from the lipid-oligosaccharide intermediates to the nascent polypeptide chain. The data presented also provide evidence that the lipid-saccharide intermediates, previously described mainly in in vitro systems, are in fact involved in the glycosylation of a majority, if not all, of the mannose-containing glycoproteins in intact, growing hamster cells.", "contents": "Lipid-saccharide intermediates and glycoprotein biosynthesis in a temperature-sensitive Chinese hamster cell mutant. The characterization of a temperature-sensitive Chinese hamster cell mutant has been continued with the aim of localizing the apparent defect in glycoprotein synthesis (Tenner et al., '77). Although the mutation is lethal, a demonstration of the ability of the mutant cells to support proliferation of Mengo virus at the nonpermissive temperature indicates that the general metabolic processes of the cells remain intact at a time when glycoprotein synthesis is severely depressed. A quantitative study of protein synthesis on membrane-associated polysomes suggests that the synthesis of the polypeptide portion of the glycoproteins at 40.8 degrees C may be normal. The investigation of lipid-saccharide molecules which have been implicated in the formation and transfer of the oligosaccharide \"core\" to polypeptide acceptors shows that mutant cells at the nonpermissive temperature are capable of synthesizing these lipid saccharides normally, and that the pool of the dolichyl oligosaccharides is maintained at a constant level independent of the temperature. The rate of formation of the lipid-oligosaccharide, however, is reduced in intact mutant cells at the nonpermissive temperature. Further investigations show this decreased rate to be the result of an increased half life of the lipid-oligosaccharide at 40.8 degrees C. These data indicate that the temperature-sensitive step in glycoprotein biosynthesis is the transfer of the oligosaccharide core from the lipid-oligosaccharide intermediates to the nascent polypeptide chain. The data presented also provide evidence that the lipid-saccharide intermediates, previously described mainly in in vitro systems, are in fact involved in the glycosylation of a majority, if not all, of the mannose-containing glycoproteins in intact, growing hamster cells."}
{"id": "PMID:217885", "title": "Production of serum proteins in normal diploid fibroblast-hepatoma cell hybrids and in A9-normal liver cell hybrids.", "content": "Two series of interspecific hybrids have been generated between liver cells (which actively secrete several serum proteins) and fibroblasts (which do not). In each series, one of the parental cells was a normal diploid cell: mouse hepatoma cells were fused with normal diploid rat fibroblasts, and normal rat liver cells were fused with mouse fibroblasts of the permanent line A9. The production of albumin, alpha-fetoprotein (AFP) transferrin and the third component of complement (C3) was analysed in these hybrids. Most hepatoma cell hybrids exhibit extinction of albumin, AFP and (to a lesser extent) transferrin; they retain the capacity to secrete C3. Normal liver cell hybrids are also characterized by the absence of albumin and transferrin production and by retention of C3 secretion. These results, when compared to previous results obtained with hybrids derived exclusively from different differentiated cells of permanent and transformed lines show that the phenotype of such hybrids is not determined by the abnormal character per se of the aneuploid parental cells. Amongst the rat fibroblast-mouse hepatoma cell hybrids, a few clones retain the capacity to actively secrete mouse albumin, AFP and transferrin, without the concomitant production of the rat serum proteins. These hybrids have lost more rat (fibroblast) chromosomes than the other clones and also have an increased number of mouse (hepatoma) chromosomes. Thus, their phenotype must result from either the complete loss of 'extinguisher' chromosomes, or gene dosage effects. The significance of the lack of rat serum protein production is also discussed, and it is suggested that retention, without concomitant activation, could be explained in terms of diffusible regulators and heritable differences in chromatin conformation.", "contents": "Production of serum proteins in normal diploid fibroblast-hepatoma cell hybrids and in A9-normal liver cell hybrids. Two series of interspecific hybrids have been generated between liver cells (which actively secrete several serum proteins) and fibroblasts (which do not). In each series, one of the parental cells was a normal diploid cell: mouse hepatoma cells were fused with normal diploid rat fibroblasts, and normal rat liver cells were fused with mouse fibroblasts of the permanent line A9. The production of albumin, alpha-fetoprotein (AFP) transferrin and the third component of complement (C3) was analysed in these hybrids. Most hepatoma cell hybrids exhibit extinction of albumin, AFP and (to a lesser extent) transferrin; they retain the capacity to secrete C3. Normal liver cell hybrids are also characterized by the absence of albumin and transferrin production and by retention of C3 secretion. These results, when compared to previous results obtained with hybrids derived exclusively from different differentiated cells of permanent and transformed lines show that the phenotype of such hybrids is not determined by the abnormal character per se of the aneuploid parental cells. Amongst the rat fibroblast-mouse hepatoma cell hybrids, a few clones retain the capacity to actively secrete mouse albumin, AFP and transferrin, without the concomitant production of the rat serum proteins. These hybrids have lost more rat (fibroblast) chromosomes than the other clones and also have an increased number of mouse (hepatoma) chromosomes. Thus, their phenotype must result from either the complete loss of 'extinguisher' chromosomes, or gene dosage effects. The significance of the lack of rat serum protein production is also discussed, and it is suggested that retention, without concomitant activation, could be explained in terms of diffusible regulators and heritable differences in chromatin conformation."}
{"id": "PMID:217886", "title": "Action of a slowly hydrolysable cyclic AMP analogue on developing cells of Dictyostelium discoideum.", "content": "Adenosine 3',5'-cyclic phosphorothioate (cAMP-S) is a cyclic AMP (cAMP) analogue which is only slowly hydrolysed by phosphodiesterases of Dictyostelium discoideum. The affinity of cAMP-S to cAMP receptors at the cell surface is only one order of magnitude lower than that of cAMP. cAMP-S can replace cAMP as a stimulant with respect to all receptor-mediated responses tested, including chemotaxis and the induction of cAMP pulses. cAMP-S does not affect growth of D. discoideum but it blocks cell aggregation at a uniform concentration of 5 x 10(-7) M in agar plate cultures of strain NC-4 as well as its axenically growing derivative, Ax-2. Another wild-type strain of D. discoideum, v-12, is able to aggregate on agar plates supplemented with 1 mM cAMP-S. The development of Polysphondylium pallidum and P. violaceum is also highly cAMP-S resistant. In Ax-2 both differentiation from the growth phase to the aggregation-competent stage and chemotaxis are cAMP-S sensitive, whereas in v-12 only chemotaxis is inhibited. v-12 can still form streams of cohering cells and fruiting bodies when chemotaxis is inhibited by cAMP-S. Whereas cAMP induces differentiation into stalk cells at concentrations of 10(-3) or 10(-4) M, cAMP-S has the same effect in strain v-12 at the much lower concentration of 10(-6) M.", "contents": "Action of a slowly hydrolysable cyclic AMP analogue on developing cells of Dictyostelium discoideum. Adenosine 3',5'-cyclic phosphorothioate (cAMP-S) is a cyclic AMP (cAMP) analogue which is only slowly hydrolysed by phosphodiesterases of Dictyostelium discoideum. The affinity of cAMP-S to cAMP receptors at the cell surface is only one order of magnitude lower than that of cAMP. cAMP-S can replace cAMP as a stimulant with respect to all receptor-mediated responses tested, including chemotaxis and the induction of cAMP pulses. cAMP-S does not affect growth of D. discoideum but it blocks cell aggregation at a uniform concentration of 5 x 10(-7) M in agar plate cultures of strain NC-4 as well as its axenically growing derivative, Ax-2. Another wild-type strain of D. discoideum, v-12, is able to aggregate on agar plates supplemented with 1 mM cAMP-S. The development of Polysphondylium pallidum and P. violaceum is also highly cAMP-S resistant. In Ax-2 both differentiation from the growth phase to the aggregation-competent stage and chemotaxis are cAMP-S sensitive, whereas in v-12 only chemotaxis is inhibited. v-12 can still form streams of cohering cells and fruiting bodies when chemotaxis is inhibited by cAMP-S. Whereas cAMP induces differentiation into stalk cells at concentrations of 10(-3) or 10(-4) M, cAMP-S has the same effect in strain v-12 at the much lower concentration of 10(-6) M."}
{"id": "PMID:217888", "title": "Pseudocorpus luteum insufficiency: a local defect of progesterone action on endometrial stroma.", "content": "A 23-yr-old woman whose initial complaint was infertility demonstrated glandular stromal dissociation with failure of the endometrial stroma to undergo pseudodecidualization in repeated endometrial biopsies taken late in the luteal phase. As the clinical presentation was consistent with the inadequate corpus luteum syndrome, hormone measurements were performed. The endometrial biopsy was abnormal during cycles in which the serum pattern of progesterone, estradiol, FSH, and LH was normal. Exogenous progesterone did not correct the abnormality. The patient, by in vitro studies, has approximately one half the number of high affinity progesterone-binding sites in the cytosol fraction of her endometrium compared to preparations from two normal control subjects. Since her cytosol-binding protein was qualitatively identical to two control subjects, the incomplete maturation of her endometrial stroma may represent an absence or reduced number of stromal cytosol receptors and/or a resistance to specific hormone action in an individual target tissue.", "contents": "Pseudocorpus luteum insufficiency: a local defect of progesterone action on endometrial stroma. A 23-yr-old woman whose initial complaint was infertility demonstrated glandular stromal dissociation with failure of the endometrial stroma to undergo pseudodecidualization in repeated endometrial biopsies taken late in the luteal phase. As the clinical presentation was consistent with the inadequate corpus luteum syndrome, hormone measurements were performed. The endometrial biopsy was abnormal during cycles in which the serum pattern of progesterone, estradiol, FSH, and LH was normal. Exogenous progesterone did not correct the abnormality. The patient, by in vitro studies, has approximately one half the number of high affinity progesterone-binding sites in the cytosol fraction of her endometrium compared to preparations from two normal control subjects. Since her cytosol-binding protein was qualitatively identical to two control subjects, the incomplete maturation of her endometrial stroma may represent an absence or reduced number of stromal cytosol receptors and/or a resistance to specific hormone action in an individual target tissue."}
{"id": "PMID:217890", "title": "Heterogeneity of the human chorionic gonadotropin alpha-subunit secreted by cultured choriocarcinoma (JEG) cells.", "content": "The cultured human choriocarcinoma cell line, JEG-clone 3, secretes substantial quantities of both biologically active hCG and an immunoreactive alpha-subunit (JEG-alpha). This study is concerned with a comparative characterization, using RIA, of the chromatographic properties (via gel exclusion and isoelectric focusing) of JEG-alpha and standard urinary hCG-alpha. Most of the molecules comprising the JEG-alpha fraction have an apparent molecular weight greater than that of hCG-alpha. Both hCG-alpha and JEG-alpha exhibit heterogeneity on electrofocusing. However, JEG-alpha contains a major component with an isoelectric pH (pI) of 4.8; this is a minor component, if present at all, in hCG-alpha. The JEG-alpha pI 4.8 component chromatographs with an apparent molecular weight greater than hCG-alpha, while a minor JEG-alpha pI 7.0 component chromatographs with an apparent molecular weight similar to that of the standard. Heterogeneity is expected in the carbohydrate moieties of the glycoprotein hormone subunits. Results of studies on the incorporation of 14C- and 3H labeled amino acids into JEG-alpha suggest that heterogeneity also exists in the protein moiety of JEG-alpha. An interesting possibility is that the form(s) of JEG-alpha with larger apparent molecular weight represents a precursor of the alpha-subunit used to form hCG.", "contents": "Heterogeneity of the human chorionic gonadotropin alpha-subunit secreted by cultured choriocarcinoma (JEG) cells. The cultured human choriocarcinoma cell line, JEG-clone 3, secretes substantial quantities of both biologically active hCG and an immunoreactive alpha-subunit (JEG-alpha). This study is concerned with a comparative characterization, using RIA, of the chromatographic properties (via gel exclusion and isoelectric focusing) of JEG-alpha and standard urinary hCG-alpha. Most of the molecules comprising the JEG-alpha fraction have an apparent molecular weight greater than that of hCG-alpha. Both hCG-alpha and JEG-alpha exhibit heterogeneity on electrofocusing. However, JEG-alpha contains a major component with an isoelectric pH (pI) of 4.8; this is a minor component, if present at all, in hCG-alpha. The JEG-alpha pI 4.8 component chromatographs with an apparent molecular weight greater than hCG-alpha, while a minor JEG-alpha pI 7.0 component chromatographs with an apparent molecular weight similar to that of the standard. Heterogeneity is expected in the carbohydrate moieties of the glycoprotein hormone subunits. Results of studies on the incorporation of 14C- and 3H labeled amino acids into JEG-alpha suggest that heterogeneity also exists in the protein moiety of JEG-alpha. An interesting possibility is that the form(s) of JEG-alpha with larger apparent molecular weight represents a precursor of the alpha-subunit used to form hCG."}
{"id": "PMID:217891", "title": "Adrenocorticotropin-cortisol axis abnormalities in hemodialysis patients.", "content": "The ACTH-cortisol axis was studied in 15 hemodialysis patients. Basal plasma cortisol concentrations were found to be elevated and ACTH to be in the high normal range. Cortisol responded normally to exogenous ACTH, but neither cortisol nor ACTH were suppressed in response to oral dexamethasone. 11-Deoxycortisol and ACTH concentrations did not rise normally in response to either oral or iv metyrapone. We conclude that standard testing of the ACTH-cortisol axis in dialysis patients yields results suggesting Cushing's syndrome.", "contents": "Adrenocorticotropin-cortisol axis abnormalities in hemodialysis patients. The ACTH-cortisol axis was studied in 15 hemodialysis patients. Basal plasma cortisol concentrations were found to be elevated and ACTH to be in the high normal range. Cortisol responded normally to exogenous ACTH, but neither cortisol nor ACTH were suppressed in response to oral dexamethasone. 11-Deoxycortisol and ACTH concentrations did not rise normally in response to either oral or iv metyrapone. We conclude that standard testing of the ACTH-cortisol axis in dialysis patients yields results suggesting Cushing's syndrome."}
{"id": "PMID:217892", "title": "Enzyme-linked immunosorbent assay for detection of antibodies to influenza A and B and parainfluenza type 1 in sera of patients.", "content": "An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of antibodies to influenza A/Hong Kong/1/68, influenza A/Victoria/3/75, influenza B/Hong Kong/5/72, and parainfluenza type 1 viruses. Development and standardization of the method indicated that an acetone-ethyl alcohol mixture was a suitable fixative for the preparation of the solid-phase coupled antigen. The addition of sodium azide to the enzyme-conjugated solution and the concentrations of the enzyme-conjugate antiglobulin and test sera employed were all critical factors in the success of the ELISA procedure. The ELISA test was specific; there was no cross-reaction between influenza A and B or parainfluenza type 1 viruses. The concordance between ELISA and hemagglutination inhibition results suggested that both tests probably detected the same type of antibodies. The ELISA procedure was 8 to 64 times more sensitive than complement fixation and/or hemagglutination inhibition tests. Low levels of antibody in patients' sera were detected only by the ELISA test. During the course of the testing period false positive reactions were not encountered. The results of ELISA could be obtained within 3 h. The ELISA test required a very small amount of serum and, therefore, offered an opportunity to detect the presence of maternal antibodies to influenza viruses in blood collected from infants by heel prick.", "contents": "Enzyme-linked immunosorbent assay for detection of antibodies to influenza A and B and parainfluenza type 1 in sera of patients. An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of antibodies to influenza A/Hong Kong/1/68, influenza A/Victoria/3/75, influenza B/Hong Kong/5/72, and parainfluenza type 1 viruses. Development and standardization of the method indicated that an acetone-ethyl alcohol mixture was a suitable fixative for the preparation of the solid-phase coupled antigen. The addition of sodium azide to the enzyme-conjugated solution and the concentrations of the enzyme-conjugate antiglobulin and test sera employed were all critical factors in the success of the ELISA procedure. The ELISA test was specific; there was no cross-reaction between influenza A and B or parainfluenza type 1 viruses. The concordance between ELISA and hemagglutination inhibition results suggested that both tests probably detected the same type of antibodies. The ELISA procedure was 8 to 64 times more sensitive than complement fixation and/or hemagglutination inhibition tests. Low levels of antibody in patients' sera were detected only by the ELISA test. During the course of the testing period false positive reactions were not encountered. The results of ELISA could be obtained within 3 h. The ELISA test required a very small amount of serum and, therefore, offered an opportunity to detect the presence of maternal antibodies to influenza viruses in blood collected from infants by heel prick."}
{"id": "PMID:217893", "title": "Antibody to varicella-zoster virus after passive immunization against chickenpox.", "content": "Antibody titers to varicella-zoster virus were measured in varicella-susceptible immunocompromised children 48 h after they received either one of two lots of zoster immune globulin (ZIG) or a selected lot of immune serum globulin (ISG). Globulin was given to modify varicella in these children after exposure to varicella or zoster. Indirect immunofluorescence antibody titers (FAMA) of children after receipt of globulin ranged from less than 1:2 to 1:32. Geometric mean FAMA titers were highest after 1.2 ml of ISG per kg (FAMA titer 1:128) and 0.16 ml of ZIG lot A per kg (FAMA titer 1:1,024). Selected batches of ISG titering 1:128 or greater by FAMA, at a dose of 1.2 ml/kg, may be used to attempt to modify varicella in susceptible high-risk individuals when ZIG is not available.", "contents": "Antibody to varicella-zoster virus after passive immunization against chickenpox. Antibody titers to varicella-zoster virus were measured in varicella-susceptible immunocompromised children 48 h after they received either one of two lots of zoster immune globulin (ZIG) or a selected lot of immune serum globulin (ISG). Globulin was given to modify varicella in these children after exposure to varicella or zoster. Indirect immunofluorescence antibody titers (FAMA) of children after receipt of globulin ranged from less than 1:2 to 1:32. Geometric mean FAMA titers were highest after 1.2 ml of ISG per kg (FAMA titer 1:128) and 0.16 ml of ZIG lot A per kg (FAMA titer 1:1,024). Selected batches of ISG titering 1:128 or greater by FAMA, at a dose of 1.2 ml/kg, may be used to attempt to modify varicella in susceptible high-risk individuals when ZIG is not available."}
{"id": "PMID:217895", "title": "The use of iodolipids in hepatosplenic computed tomography.", "content": "Iodolipids have been used as a contrast medium for hepatosplenic computed tomography (CT) in 148 patients. In all but two of these cases, the contrast material was injected by the intravenous route. The method appears to be safe due to the marked reduction of dosage in CT compared with conventional radiographic iodolipid hepatography. This decreased dosage is made possible by the improved density and spatial resolution of CT. Pictorial and histographic densitometric analysis of normal and abnormal liver after iodolipid administration yields considerable diagnostic improvement.", "contents": "The use of iodolipids in hepatosplenic computed tomography. Iodolipids have been used as a contrast medium for hepatosplenic computed tomography (CT) in 148 patients. In all but two of these cases, the contrast material was injected by the intravenous route. The method appears to be safe due to the marked reduction of dosage in CT compared with conventional radiographic iodolipid hepatography. This decreased dosage is made possible by the improved density and spatial resolution of CT. Pictorial and histographic densitometric analysis of normal and abnormal liver after iodolipid administration yields considerable diagnostic improvement."}
{"id": "PMID:217896", "title": "Development and experimental evaluation of a contrast medium for computed tomographic examination of the liver and spleen.", "content": "A lipoid based contrast material containing 53% of ethiodized oil in emulsion form was developed for computed tomography (CT) of the liver and spleen and tested in rabbits and monkeys. An intravenous dose of 0.2 ml/kg selectively opacified the liver and spleen, resulting in an average increase of 23 EMI units (500 scales) in the attenuation of the liver and a higher increase in the attenuation of the spleen. When injected into rhesus monkeys with carcinogen induced hepatomas there was a significant improvement in the visualization of the tumor, and small lesions, undetectable on the preliminary CT scan, became visible. Toxicity studies are in progress.", "contents": "Development and experimental evaluation of a contrast medium for computed tomographic examination of the liver and spleen. A lipoid based contrast material containing 53% of ethiodized oil in emulsion form was developed for computed tomography (CT) of the liver and spleen and tested in rabbits and monkeys. An intravenous dose of 0.2 ml/kg selectively opacified the liver and spleen, resulting in an average increase of 23 EMI units (500 scales) in the attenuation of the liver and a higher increase in the attenuation of the spleen. When injected into rhesus monkeys with carcinogen induced hepatomas there was a significant improvement in the visualization of the tumor, and small lesions, undetectable on the preliminary CT scan, became visible. Toxicity studies are in progress."}
{"id": "PMID:217897", "title": "Primary malignant fibrous histiocytoma of skin.", "content": "Three fibrous histiocytomas, primary in skin, were studied by light and electron microscopy and by frozen section histochemistry. The term malignant was applied to cutaneous tumors which demonstrated aggressive multinodular local growth, including angioinvasion and/or extension into bone, muscle, and fascia. Metastases were not found. Strongly positive reactions for hydrolytic enzymes, particularly acid phosphatase will help differentiate malignant fibrous histiocytoma from most other primary soft tissue malignancies of skin. Electron microscopic studies reaffirm the presence of both histiocyte-like and fibroblast-like cells. Langerhans' granules were not identified. Primary malignant fibrous histiocytoma of skin may have a prognosis superior to homologous tumors arising in deeper soft tissue and the retroperitoneum.", "contents": "Primary malignant fibrous histiocytoma of skin. Three fibrous histiocytomas, primary in skin, were studied by light and electron microscopy and by frozen section histochemistry. The term malignant was applied to cutaneous tumors which demonstrated aggressive multinodular local growth, including angioinvasion and/or extension into bone, muscle, and fascia. Metastases were not found. Strongly positive reactions for hydrolytic enzymes, particularly acid phosphatase will help differentiate malignant fibrous histiocytoma from most other primary soft tissue malignancies of skin. Electron microscopic studies reaffirm the presence of both histiocyte-like and fibroblast-like cells. Langerhans' granules were not identified. Primary malignant fibrous histiocytoma of skin may have a prognosis superior to homologous tumors arising in deeper soft tissue and the retroperitoneum."}
{"id": "PMID:217898", "title": "Adrenal responsiveness in pre- and postpartum dairy cows.", "content": "Adrenal responsiveness was evaluated by injecting 10 multiparous dairy cows with 200 IU adrenocorticotropin between -13 and -2 days prepartum (I) and postpartum between 24 and 40 h (II) and 21 and 24 days (III). Concentrations of glucocorticoids following injection were influenced by day of injection, temperature, and minimum percent relative humidity but not by breed, breed X injection day interaction, or age of cow. Likewise differences in regressions for adrenal response and mean response (ng/ml) for the three injections were nil. Mean concentrations at peak (45, 60, and 120 min postinjection samples) adjusted for preinjection concentrations also did not differ for the three periods of injection. Mean concentrations of glucocorticoids in plasma for daily samples between -13 and -2 days prepartum were 5.3 +/- .4 (n = 61), reached a peak of 14.8 +/- .3 ng/ml the day of calving, and remained high for 2 days postpartum. Estradiol increased through prepartum sampling from 23.3 to 339.6 +/- 94.1 pg/ml the day of calving, then declined abruptly. Progestins began to decline about -5 days prepartum from mean concentration of 4.09 +/- .62 (n = 25) and attained low concentrations (.30 +/- .06 ng/ml) 2 days postpartum. Although there was a surge of glucocorticoids at parturition, this was not associated with a modification in adrenal responsiveness or with prepartum concentrations of other steroid hormones of plasma. Adrenal potential in prepartum and postpartum dairy cows appears well maintained.", "contents": "Adrenal responsiveness in pre- and postpartum dairy cows. Adrenal responsiveness was evaluated by injecting 10 multiparous dairy cows with 200 IU adrenocorticotropin between -13 and -2 days prepartum (I) and postpartum between 24 and 40 h (II) and 21 and 24 days (III). Concentrations of glucocorticoids following injection were influenced by day of injection, temperature, and minimum percent relative humidity but not by breed, breed X injection day interaction, or age of cow. Likewise differences in regressions for adrenal response and mean response (ng/ml) for the three injections were nil. Mean concentrations at peak (45, 60, and 120 min postinjection samples) adjusted for preinjection concentrations also did not differ for the three periods of injection. Mean concentrations of glucocorticoids in plasma for daily samples between -13 and -2 days prepartum were 5.3 +/- .4 (n = 61), reached a peak of 14.8 +/- .3 ng/ml the day of calving, and remained high for 2 days postpartum. Estradiol increased through prepartum sampling from 23.3 to 339.6 +/- 94.1 pg/ml the day of calving, then declined abruptly. Progestins began to decline about -5 days prepartum from mean concentration of 4.09 +/- .62 (n = 25) and attained low concentrations (.30 +/- .06 ng/ml) 2 days postpartum. Although there was a surge of glucocorticoids at parturition, this was not associated with a modification in adrenal responsiveness or with prepartum concentrations of other steroid hormones of plasma. Adrenal potential in prepartum and postpartum dairy cows appears well maintained."}
{"id": "PMID:217894", "title": "Effects of 3-hydroxy-3-methylglutaric acid on plasma and low-density lipoprotein cholesterol levels in familial hypercholesterolemia.", "content": "Different doses of 3-hydroxy-3-methyl-glutaric acid (HMG) on plasma lipids were studied in a double-blind trial in 36 patients with familial hypercholesterolemia (type IIa or hyper-beta-lipoproteinemia). The patients were randomly assigned to five groups, and each group received one of the following treatments: placebo, or HMG 750 mg, 1500 mg, 2250 mg, or 3000 mg per day. As compared to placebo, the mean plasma cholesterol levels during the eight-week treatment period were 11 and 13 per cent lower in the 2250-mg and 3000-mg HMG-treated groups (P less than 0.034 and less than 0.021, respectively). At the same dosage levels LDL cholesterol was decreased by 8 per cent. HMG had no significant effect on plasma triglycerides as compared to placebo. Discontinuation of the medication did not result in a rebound of plasma cholesterol. There were no clinical or biologic adverse effects due to the administration of HMG, and all patients maintained excellent compliance to the medication. Because of its lack of toxicity, HMG may be useful as an adjunct to diet in the treatment of familial hypercholesterolemia.", "contents": "Effects of 3-hydroxy-3-methylglutaric acid on plasma and low-density lipoprotein cholesterol levels in familial hypercholesterolemia. Different doses of 3-hydroxy-3-methyl-glutaric acid (HMG) on plasma lipids were studied in a double-blind trial in 36 patients with familial hypercholesterolemia (type IIa or hyper-beta-lipoproteinemia). The patients were randomly assigned to five groups, and each group received one of the following treatments: placebo, or HMG 750 mg, 1500 mg, 2250 mg, or 3000 mg per day. As compared to placebo, the mean plasma cholesterol levels during the eight-week treatment period were 11 and 13 per cent lower in the 2250-mg and 3000-mg HMG-treated groups (P less than 0.034 and less than 0.021, respectively). At the same dosage levels LDL cholesterol was decreased by 8 per cent. HMG had no significant effect on plasma triglycerides as compared to placebo. Discontinuation of the medication did not result in a rebound of plasma cholesterol. There were no clinical or biologic adverse effects due to the administration of HMG, and all patients maintained excellent compliance to the medication. Because of its lack of toxicity, HMG may be useful as an adjunct to diet in the treatment of familial hypercholesterolemia."}
{"id": "PMID:217899", "title": "The fate of amalgam implanted in soft tissues -- an experimental study.", "content": "The soft tissue reaction to amalgam depended on whether it was finely ground or a solid mass. Finely ground amalgam was actively digested within macrophages and giant-cells with loss of mercury and the formation of the fine particles of silver and sulphur. Larger masses became surrounded by a fibrous capsule.", "contents": "The fate of amalgam implanted in soft tissues -- an experimental study. The soft tissue reaction to amalgam depended on whether it was finely ground or a solid mass. Finely ground amalgam was actively digested within macrophages and giant-cells with loss of mercury and the formation of the fine particles of silver and sulphur. Larger masses became surrounded by a fibrous capsule."}
{"id": "PMID:217903", "title": "Quantitation of mitochondrial DNA and protein in the liver of Fischer 344 rats during aging.", "content": "Mitochondria from liver whole homogenates of Fischer 344 rats, 3,6, 12 and 24 mo of age were separated by reorienting rate-zonal centrifugation on sucrose gradients. Employing this method, mitochondria can be harvested nearly quantitatively and subjected to a number of biochemical analyses. Separation and recovery of the mitochondria from young and old rats was monitored by assaying each fraction from the gradient for cytochrome oxidase and lipoamide dehydrogenase, two mitochondrial specific enzymes. In addition, several regions of the gradient were studied by transmission electron microscopy. In this study, mitochondrial DNA and protein were quantitated from the livers of the animals at each age group. It was demonstrated that between the ages of 12 and 24 mo these macromolecules decreased significantly. These data would seem to indicate that the number of mitochondria is decreased in this tissue in aged animals.", "contents": "Quantitation of mitochondrial DNA and protein in the liver of Fischer 344 rats during aging. Mitochondria from liver whole homogenates of Fischer 344 rats, 3,6, 12 and 24 mo of age were separated by reorienting rate-zonal centrifugation on sucrose gradients. Employing this method, mitochondria can be harvested nearly quantitatively and subjected to a number of biochemical analyses. Separation and recovery of the mitochondria from young and old rats was monitored by assaying each fraction from the gradient for cytochrome oxidase and lipoamide dehydrogenase, two mitochondrial specific enzymes. In addition, several regions of the gradient were studied by transmission electron microscopy. In this study, mitochondrial DNA and protein were quantitated from the livers of the animals at each age group. It was demonstrated that between the ages of 12 and 24 mo these macromolecules decreased significantly. These data would seem to indicate that the number of mitochondria is decreased in this tissue in aged animals."}
{"id": "PMID:217905", "title": "An unusual complication following surgical treatment of deQuervain's disease.", "content": "Symptoms of deQuervain's disease were relieved by incision of the first dorsal compartment sheath in a 43-year-old hospital employee. Three months after the operation she developed dysaesthesias in the distribution of the superficial radial nerve with wrist extension and thumb abduction. At reoperation the tendons of the first dorsal compartment were found to glide dorsally onto a fibrous remnant of the sheath and to elevate the overlying superficial radial nerve. Excision of the fibrous ridge resulted in relief of symptoms. The complication could have been avoided, in retrospect, by excising the sheath or by incising it at its dorsal attachment.", "contents": "An unusual complication following surgical treatment of deQuervain's disease. Symptoms of deQuervain's disease were relieved by incision of the first dorsal compartment sheath in a 43-year-old hospital employee. Three months after the operation she developed dysaesthesias in the distribution of the superficial radial nerve with wrist extension and thumb abduction. At reoperation the tendons of the first dorsal compartment were found to glide dorsally onto a fibrous remnant of the sheath and to elevate the overlying superficial radial nerve. Excision of the fibrous ridge resulted in relief of symptoms. The complication could have been avoided, in retrospect, by excising the sheath or by incising it at its dorsal attachment."}
{"id": "PMID:217906", "title": "Syndactyly with Larsen's syndrome.", "content": "The association of syndactyly with Larsen's syndrome is reported. A revised listing of syndromes which may be associated with syndactyly is presented.", "contents": "Syndactyly with Larsen's syndrome. The association of syndactyly with Larsen's syndrome is reported. A revised listing of syndromes which may be associated with syndactyly is presented."}
{"id": "PMID:217927", "title": "Coping with cancer through self-instruction: a hypothesis.", "content": "Because most cancer patients seem to cope well with the stresses of their illness, including the psychosocial ramifications, it is important to understand what good copers manage to do, as opposed to those patients who simply defend themselves against persistent problems. This requires making a radical distinction between coping and defending, as well as between healthy adaptive resources and latent pathological dispositions. A case report is presented to illustrate how one \"supercoper\" solved problems by self-instruction. While cognitive self-instruction may not be applicable for every cancer patient and all problems, it is a working hypothesis deserving of further investigation, since self-control and personal responsibility are essential elements in rehabilitation on all levels. One intervention model for \"high distress\" cancer patients is outlined.", "contents": "Coping with cancer through self-instruction: a hypothesis. Because most cancer patients seem to cope well with the stresses of their illness, including the psychosocial ramifications, it is important to understand what good copers manage to do, as opposed to those patients who simply defend themselves against persistent problems. This requires making a radical distinction between coping and defending, as well as between healthy adaptive resources and latent pathological dispositions. A case report is presented to illustrate how one \"supercoper\" solved problems by self-instruction. While cognitive self-instruction may not be applicable for every cancer patient and all problems, it is a working hypothesis deserving of further investigation, since self-control and personal responsibility are essential elements in rehabilitation on all levels. One intervention model for \"high distress\" cancer patients is outlined."}
{"id": "PMID:217928", "title": "Enteric viruses in the Danube river water and sludge.", "content": "A study of the viral pollution of the Roumanian course of the Danube river was carried out from 1972 to 1974. The presence of enteric viruses was investigated in 123 water samples, taken by the gauze swab method and in 116 sludge samples from the bottom of the river. The samples were collected from 20 sampling points along the river from Moldova Veche to Br\u0103ila, in accordance with the water use and the main pollution sources. Viruses were recovered from 17.5% of the samples. The frequency of virus isolations from water samples was similar to that observed in sludge samples. Therefore, the viral pollution of the Romanian course of the Danube showed a low level in comparison with other rivers, though two concentration techniques into suckling mice and into tissue cultures, were used for each sample.", "contents": "Enteric viruses in the Danube river water and sludge. A study of the viral pollution of the Roumanian course of the Danube river was carried out from 1972 to 1974. The presence of enteric viruses was investigated in 123 water samples, taken by the gauze swab method and in 116 sludge samples from the bottom of the river. The samples were collected from 20 sampling points along the river from Moldova Veche to Br\u0103ila, in accordance with the water use and the main pollution sources. Viruses were recovered from 17.5% of the samples. The frequency of virus isolations from water samples was similar to that observed in sludge samples. Therefore, the viral pollution of the Romanian course of the Danube showed a low level in comparison with other rivers, though two concentration techniques into suckling mice and into tissue cultures, were used for each sample."}
{"id": "PMID:217904", "title": "[The radio immune level of total serum oestriol during pregnancy. An examination of the method and comparison of the concentrations of total serum oestriol, non-conjugated serum oestriol and the excretion of total urinary oestrogens (author's transl)].", "content": "The authors report on a preliminary study of the level of total serum oestriol in the third trimester of pregnancy by the bundle method of estimating this with \"oestriol 1251 RIA Kit\" (Amersham, Buchler). The criteria on which the quality of the method depends, viz, sensitivity, specificity, reliability, and accuracy, together with its practicability are satisfactory. Correlations between total serum oestriol and free serum oestriol and total urinary oestrogens are good and correspond with those given in the literature. This method therefore can be used in clinical practice. All the same, it still has to be established which parameter better reflects the feto-placental state. Is it the free serum oestriol or the total serum oestriol?", "contents": "[The radio immune level of total serum oestriol during pregnancy. An examination of the method and comparison of the concentrations of total serum oestriol, non-conjugated serum oestriol and the excretion of total urinary oestrogens (author's transl)]. The authors report on a preliminary study of the level of total serum oestriol in the third trimester of pregnancy by the bundle method of estimating this with \"oestriol 1251 RIA Kit\" (Amersham, Buchler). The criteria on which the quality of the method depends, viz, sensitivity, specificity, reliability, and accuracy, together with its practicability are satisfactory. Correlations between total serum oestriol and free serum oestriol and total urinary oestrogens are good and correspond with those given in the literature. This method therefore can be used in clinical practice. All the same, it still has to be established which parameter better reflects the feto-placental state. Is it the free serum oestriol or the total serum oestriol?"}
{"id": "PMID:217929", "title": "Comparison of the efficiency of two methods for virus concentration from river water environment in a model experiment.", "content": "Two of the methodical approaches for detection of virus contamination of surface waters were experimentally tested, i.e., the method of adsorption of virus particles to an inorganic salt (CaHPO4)  and the ultrafiltration method using the Amicon apparatus. Under the given experimental conditions, the two methods showed practically identical factors of efficiency of virus concentration; the Danube river water proved to be a more suitable medium for the model of Coxsackie A4 virus than the physiological saline used as the control. In view of the feasibility, inexpensiveness and adequate effectivity of the precipitation method and with respect to good results obtained with it in field studies, the mentioned method of concentration could be recommended as the method of choice in field virological practice for aimed examination of surface waters.", "contents": "Comparison of the efficiency of two methods for virus concentration from river water environment in a model experiment. Two of the methodical approaches for detection of virus contamination of surface waters were experimentally tested, i.e., the method of adsorption of virus particles to an inorganic salt (CaHPO4)  and the ultrafiltration method using the Amicon apparatus. Under the given experimental conditions, the two methods showed practically identical factors of efficiency of virus concentration; the Danube river water proved to be a more suitable medium for the model of Coxsackie A4 virus than the physiological saline used as the control. In view of the feasibility, inexpensiveness and adequate effectivity of the precipitation method and with respect to good results obtained with it in field studies, the mentioned method of concentration could be recommended as the method of choice in field virological practice for aimed examination of surface waters."}
{"id": "PMID:217930", "title": "Coxsackie A 13 virus in the foci of rheumatism.", "content": "Faeces and nasopharyngeal washing were examined in 12 patients and 27 contacts of these patients in family foci (primary foci) of rheumatism and in 37 patients and 32 contacts of these patients in secondary foci of rheumatism (in hospitals). Results of stimultaneous examinations of 127 children of the control groups served as the control. An analysis of the results of the investigation showed the Coxsackie A 13 virus was found considerably more frequently in both the patients (83.3%) and their contacts (148.1%) in the primary foci of rheumatism than outside these foci (11.9--15.3%). The difference is statistically significant. Wide distribution of Coxsackie A 13 virus was also observed in clinical departments in which children were hospitalized at the acute stage of rheumatism. We failed to establish marked differences in the rate of detection of other viruses in the foci of rheumatism in comparison with the control groups.", "contents": "Coxsackie A 13 virus in the foci of rheumatism. Faeces and nasopharyngeal washing were examined in 12 patients and 27 contacts of these patients in family foci (primary foci) of rheumatism and in 37 patients and 32 contacts of these patients in secondary foci of rheumatism (in hospitals). Results of stimultaneous examinations of 127 children of the control groups served as the control. An analysis of the results of the investigation showed the Coxsackie A 13 virus was found considerably more frequently in both the patients (83.3%) and their contacts (148.1%) in the primary foci of rheumatism than outside these foci (11.9--15.3%). The difference is statistically significant. Wide distribution of Coxsackie A 13 virus was also observed in clinical departments in which children were hospitalized at the acute stage of rheumatism. We failed to establish marked differences in the rate of detection of other viruses in the foci of rheumatism in comparison with the control groups."}
{"id": "PMID:217931", "title": "Production of toxic enzymes of Clostridium perfringens BP6K on technologically important media including a medium with Tween 80.", "content": "The addition of 0.05--0.1%  of Tween 80 to casein hydrolysate medium of Adams and Hendee raises and production of Clostridium perfringens BP6K lecithinase by approximately 50%. The use of the silicon antifoam Lukosan makes the medium particularly suitable for cultivation in large volumes. Higher levels of theta haemolysin and lecithinase are formed on the casein hydrolysate medium than on the meat medium. All factors except the theta and lambda components are farily stable during cultivation.", "contents": "Production of toxic enzymes of Clostridium perfringens BP6K on technologically important media including a medium with Tween 80. The addition of 0.05--0.1%  of Tween 80 to casein hydrolysate medium of Adams and Hendee raises and production of Clostridium perfringens BP6K lecithinase by approximately 50%. The use of the silicon antifoam Lukosan makes the medium particularly suitable for cultivation in large volumes. Higher levels of theta haemolysin and lecithinase are formed on the casein hydrolysate medium than on the meat medium. All factors except the theta and lambda components are farily stable during cultivation."}
{"id": "PMID:217932", "title": "Purification of hepatitis A virus by affinity chromatography.", "content": "Hepatitis A virus was purified from faeces by immunoaffinity chromatography.", "contents": "Purification of hepatitis A virus by affinity chromatography. Hepatitis A virus was purified from faeces by immunoaffinity chromatography."}
{"id": "PMID:217936", "title": "Epidermodysplasia verruciformis versus disseminated verrucae planae: is epidermodysplasia verruciformis a generalized infection with wart virus?", "content": "Recently it has been shown that epidermodysplasia verruciformis is induced by human papilloma/virus different from the papilloma/virus of warts, and that 2 distinct viruses-designated HPV-3 and HP-4--are responsible for it. Ten cases of epidermodysplasia verruciformis were found to have been caused by HPV-3. Clinically and histologically, as well as in the often depressed cell-mediated immunity they closely resembled long-standing verrucae planae, also caused by HPV-3. Contrariwise, in epidermodysplasia verruciformis caused by HPV-4 there are characteristic red, red-brown, and depigmented, pityriasis versicolor-like plaques, and malignant transformation seems almost inevitable. Cases due to HPV-3 may be abortive or even regressive, or stationary, and hard to distinguish from flat warts. No malignant conversion was seen in patients infected only with HPV-3, whereas it occurred in 2 patients infected with both viruses: HPV-3 and HPV-4. Pigmented plaques are the most important adverse prognostic sign in EV induced by HPV-3.", "contents": "Epidermodysplasia verruciformis versus disseminated verrucae planae: is epidermodysplasia verruciformis a generalized infection with wart virus? Recently it has been shown that epidermodysplasia verruciformis is induced by human papilloma/virus different from the papilloma/virus of warts, and that 2 distinct viruses-designated HPV-3 and HP-4--are responsible for it. Ten cases of epidermodysplasia verruciformis were found to have been caused by HPV-3. Clinically and histologically, as well as in the often depressed cell-mediated immunity they closely resembled long-standing verrucae planae, also caused by HPV-3. Contrariwise, in epidermodysplasia verruciformis caused by HPV-4 there are characteristic red, red-brown, and depigmented, pityriasis versicolor-like plaques, and malignant transformation seems almost inevitable. Cases due to HPV-3 may be abortive or even regressive, or stationary, and hard to distinguish from flat warts. No malignant conversion was seen in patients infected only with HPV-3, whereas it occurred in 2 patients infected with both viruses: HPV-3 and HPV-4. Pigmented plaques are the most important adverse prognostic sign in EV induced by HPV-3."}
{"id": "PMID:217937", "title": "The effect of 8-methoxypsoralen-plus ultraviolet light on cell-virus interaction: the transforming infection; effect of PUVA on the transformation of baby hamster kidney cells by polyoma virus.", "content": "Pre-treatment of baby hamster kidney (BHK) cells with 8-methoxypsoralen (8-MOP) plus ultraviolet (UV) light enhances the frequency of their transformation by polyoma (Py) virus. Of the doses tested, 0.5 microgram/ml 8-MOP plus 0.3 J/cm2 UV-light results in maximal (30-fold) stimulation of viral transformation. 8-MOP alone does not affect viral transformation and UV-light alone causes only a slight increase in the transformation frequency. Thus the drug and light act synergistically in promoting the effect. Treatment of BHK cells with drug plus light without Py infection does not lead to a transformed morphology. A drug-light combination (0.01 microgram/ml 8-MOP plus 1.2 J/cm2 UV) that inhibits cellular DNA synthesis to 75% of control at 28 hr after treatment results in a 6-fold stimulation of the transformation frequency.", "contents": "The effect of 8-methoxypsoralen-plus ultraviolet light on cell-virus interaction: the transforming infection; effect of PUVA on the transformation of baby hamster kidney cells by polyoma virus. Pre-treatment of baby hamster kidney (BHK) cells with 8-methoxypsoralen (8-MOP) plus ultraviolet (UV) light enhances the frequency of their transformation by polyoma (Py) virus. Of the doses tested, 0.5 microgram/ml 8-MOP plus 0.3 J/cm2 UV-light results in maximal (30-fold) stimulation of viral transformation. 8-MOP alone does not affect viral transformation and UV-light alone causes only a slight increase in the transformation frequency. Thus the drug and light act synergistically in promoting the effect. Treatment of BHK cells with drug plus light without Py infection does not lead to a transformed morphology. A drug-light combination (0.01 microgram/ml 8-MOP plus 1.2 J/cm2 UV) that inhibits cellular DNA synthesis to 75% of control at 28 hr after treatment results in a 6-fold stimulation of the transformation frequency."}
{"id": "PMID:217939", "title": "Serum proteins in heavily burnt patients.", "content": "Several serum proteins, such as prealbumin, protease inhibitors, immunoglobulins, metalloproteins and inflammatory glycoproteins were determined in the sera of heavily burnt patients by radial immunodiffusion. An increase of acute phase reactant glycoproteins (orsomucoid, haptoglobin, haemopexin, C-reactive protein), C3-complement, immunoglobulins, prealbumin and of the protease inhibitors (a1-antitrypsin, a2-macroglobulin) was found. For some proteins, such as prealbumin, haemopexin, immunoglobulins, this increase was preceeded by a decrease  on days 3 to 5 post-burn. The time course of the increase was variable, faster for some patients and slower for others: orosomucoid, C-reactive protein, C3-complement reached peak values between days 6 and 8; immunoglobulins and hemopexin decreased then towards normal values. No significant increase was found for ceruloplasmin, transferrin, beta2-glycoprotein, a2-SH glycoprotein and GC-globulin. It is proposed that the selective overproduction of the above mentioned proteins may be related to the stimulation of acute-phase reactant protein synthesis by the liver as a result of tissue breakdown produced by the circulating proteases and especially by elastases and collagenases as was shown previously (Miskulin et al., 1978; Moati et al., 1978a).", "contents": "Serum proteins in heavily burnt patients. Several serum proteins, such as prealbumin, protease inhibitors, immunoglobulins, metalloproteins and inflammatory glycoproteins were determined in the sera of heavily burnt patients by radial immunodiffusion. An increase of acute phase reactant glycoproteins (orsomucoid, haptoglobin, haemopexin, C-reactive protein), C3-complement, immunoglobulins, prealbumin and of the protease inhibitors (a1-antitrypsin, a2-macroglobulin) was found. For some proteins, such as prealbumin, haemopexin, immunoglobulins, this increase was preceeded by a decrease  on days 3 to 5 post-burn. The time course of the increase was variable, faster for some patients and slower for others: orosomucoid, C-reactive protein, C3-complement reached peak values between days 6 and 8; immunoglobulins and hemopexin decreased then towards normal values. No significant increase was found for ceruloplasmin, transferrin, beta2-glycoprotein, a2-SH glycoprotein and GC-globulin. It is proposed that the selective overproduction of the above mentioned proteins may be related to the stimulation of acute-phase reactant protein synthesis by the liver as a result of tissue breakdown produced by the circulating proteases and especially by elastases and collagenases as was shown previously (Miskulin et al., 1978; Moati et al., 1978a)."}
{"id": "PMID:217940", "title": "Study on the mutagenicity of conjugated estrogens in human, animal and bacterial systems.", "content": "Conjugated estrogens were studied for mutagenicity (and implied carcinogenicity) in two strains of S. typhimurium, two normal and three neoplastic human lymphoid cell lines (the latter from Burkitt's lymphoma patients) in cell culture and a Chinese hamster cell line in diffusion chambers implanted into mice. No significant increase in mutation rate or chromosome aberrations were noticed after exposure to conjugated estrogens.", "contents": "Study on the mutagenicity of conjugated estrogens in human, animal and bacterial systems. Conjugated estrogens were studied for mutagenicity (and implied carcinogenicity) in two strains of S. typhimurium, two normal and three neoplastic human lymphoid cell lines (the latter from Burkitt's lymphoma patients) in cell culture and a Chinese hamster cell line in diffusion chambers implanted into mice. No significant increase in mutation rate or chromosome aberrations were noticed after exposure to conjugated estrogens."}
{"id": "PMID:217942", "title": "Refractoriness of the pituitary gland after continuous exposure to luteinizing hormone releasing hormone.", "content": "The refractoriness of LH release by pituitary glands from intact female rats was studied during stimulation by luteinizing hormone releasing hormone (LH-RH), monobutyryl cyclic AMP+theophylline or potassium in vitro. Various concentrations of LH-RH (0.1, 0.3 and 10 ng/ml) all caused refractoriness within 24 h. Subsequent exposure to a supramaximally active concentration of LH-RH for 6 h also resulted in a depressed response; the degree of inhibition depended on the concentration of LH-RH to which the glands had been exposed previously. Glands made refractory to LH-RH also showed a depressed response to monobutyryl cyclic AMP+theophylline, although these agents by themselves were unable to induce refractoriness. Incubation in medium containing a high concentration of potassium also resulted in the release of LH, which in all respects was similar to that caused by LH-RH. Glands made refractory to LH-RH showed a decreased response to potassium and, conversely, the release of LH in response to LH-RH was reduced after exposure of glands to potassium. It is concluded that the LH releasing activity of LH-RH, which is mimicked by potassium, deteriorates during continuous exposure to the secretagogue.", "contents": "Refractoriness of the pituitary gland after continuous exposure to luteinizing hormone releasing hormone. The refractoriness of LH release by pituitary glands from intact female rats was studied during stimulation by luteinizing hormone releasing hormone (LH-RH), monobutyryl cyclic AMP+theophylline or potassium in vitro. Various concentrations of LH-RH (0.1, 0.3 and 10 ng/ml) all caused refractoriness within 24 h. Subsequent exposure to a supramaximally active concentration of LH-RH for 6 h also resulted in a depressed response; the degree of inhibition depended on the concentration of LH-RH to which the glands had been exposed previously. Glands made refractory to LH-RH also showed a depressed response to monobutyryl cyclic AMP+theophylline, although these agents by themselves were unable to induce refractoriness. Incubation in medium containing a high concentration of potassium also resulted in the release of LH, which in all respects was similar to that caused by LH-RH. Glands made refractory to LH-RH showed a decreased response to potassium and, conversely, the release of LH in response to LH-RH was reduced after exposure of glands to potassium. It is concluded that the LH releasing activity of LH-RH, which is mimicked by potassium, deteriorates during continuous exposure to the secretagogue."}
{"id": "PMID:217943", "title": "A pigeon crop sac radioreceptor assay for prolactin.", "content": "Ovine prolactin, labelled with 125I by either lactoperoxidase or a mild chloramine T method, bound to receptors from the pigeon crop sac mucosa cells of prolactin-injected pigeons. Binding was demonstrated in a crude homogenate of mucosal cells removed from the crop by scraping and in a subcellular fraction in which 5'-nucleotidase activity was enhanced two- to threefold. The binding was specific, dependent on time, temperature and the concentration of receptors and had a dissociation constant of 7 X 10(-10) mol/l. The binding capacity of the crop tissue was 71 fmol/mg membrane protein. Nine purified preparations of prolactin from four species were assayed by local pigeon crop sac bioassay and by radioreceptor assay. The two methods were highly correlated (r = 0.934). The regression equation was radioreceptor assay = 1.22 bioassay--0.18 indicating a 1 : 1 correspondence between the two methods for prolactin purified from sheep, rat, horse and pig anterior pituitary glands.", "contents": "A pigeon crop sac radioreceptor assay for prolactin. Ovine prolactin, labelled with 125I by either lactoperoxidase or a mild chloramine T method, bound to receptors from the pigeon crop sac mucosa cells of prolactin-injected pigeons. Binding was demonstrated in a crude homogenate of mucosal cells removed from the crop by scraping and in a subcellular fraction in which 5'-nucleotidase activity was enhanced two- to threefold. The binding was specific, dependent on time, temperature and the concentration of receptors and had a dissociation constant of 7 X 10(-10) mol/l. The binding capacity of the crop tissue was 71 fmol/mg membrane protein. Nine purified preparations of prolactin from four species were assayed by local pigeon crop sac bioassay and by radioreceptor assay. The two methods were highly correlated (r = 0.934). The regression equation was radioreceptor assay = 1.22 bioassay--0.18 indicating a 1 : 1 correspondence between the two methods for prolactin purified from sheep, rat, horse and pig anterior pituitary glands."}
{"id": "PMID:217945", "title": "A comparison of the borate-celite column screening technique with other extraction methods in forensic toxicology.", "content": "The comparison of five different extraction techniques from postmortem tissues was reported. The borate/celite column chromatography technique generally gave the best yields and its use as a screening method in forensic toxicology was discussed.", "contents": "A comparison of the borate-celite column screening technique with other extraction methods in forensic toxicology. The comparison of five different extraction techniques from postmortem tissues was reported. The borate/celite column chromatography technique generally gave the best yields and its use as a screening method in forensic toxicology was discussed."}
{"id": "PMID:217947", "title": "Effect of herpes simplex virus type 1 infection on the cellular DNA polymerase activities of mouse cell cultures.", "content": "Thymidine kinase-deficient mouse cell cultures infected with herpes simplex virus type 1 exhibited a maximum of virus DNA synthesis around 8 h post-infection as determined by pulse labelling with 3H-thymidine. Cellular DNA synthesis was progressively inhibited, but still appreciable until 8 h post-infection and not completely abolished at any time during the infectious cycle. Phosphonoacetic acid was found to be a potent and selective inhibitor of virus DNA synthesis only when added to infected cultures before the onset of virus DNA synthesis. During the interval of increasing virus DNA synthesis the activity of cellular alpha polymerase decreased rapidly, whereas the beta polymerase activity increased significantly; a slight increase was observed for the gamma polymerase activity. When infected cells were kept in the presence of phosphonoacetic acid following virus adsorption the effect on cellular DNA polymerases was less pronounced.", "contents": "Effect of herpes simplex virus type 1 infection on the cellular DNA polymerase activities of mouse cell cultures. Thymidine kinase-deficient mouse cell cultures infected with herpes simplex virus type 1 exhibited a maximum of virus DNA synthesis around 8 h post-infection as determined by pulse labelling with 3H-thymidine. Cellular DNA synthesis was progressively inhibited, but still appreciable until 8 h post-infection and not completely abolished at any time during the infectious cycle. Phosphonoacetic acid was found to be a potent and selective inhibitor of virus DNA synthesis only when added to infected cultures before the onset of virus DNA synthesis. During the interval of increasing virus DNA synthesis the activity of cellular alpha polymerase decreased rapidly, whereas the beta polymerase activity increased significantly; a slight increase was observed for the gamma polymerase activity. When infected cells were kept in the presence of phosphonoacetic acid following virus adsorption the effect on cellular DNA polymerases was less pronounced."}
{"id": "PMID:217948", "title": "Excess of interfering over infectious particles in herpes simplex virus passaged at high m.o.i. and their effect on single-cell survival.", "content": "The capacity of herpes simplex virus to kill cells and to form both infectious centres and progeny virus was studied in cell culture. Two virus stocks were compared at various m.o.i.: (i) a standard virus stock and (ii) a stock which contained interfering virus particles (I particles). The formation of infectious progeny virus as well as of infectious centres appeared to be reduced by the action of I particles. In the examined virus stock I particles exceeded infectious particles by at least a factor of 5 to 10. More than 50% of cells which could be demonstrated to be hit by I particles survived and formed colonies.", "contents": "Excess of interfering over infectious particles in herpes simplex virus passaged at high m.o.i. and their effect on single-cell survival. The capacity of herpes simplex virus to kill cells and to form both infectious centres and progeny virus was studied in cell culture. Two virus stocks were compared at various m.o.i.: (i) a standard virus stock and (ii) a stock which contained interfering virus particles (I particles). The formation of infectious progeny virus as well as of infectious centres appeared to be reduced by the action of I particles. In the examined virus stock I particles exceeded infectious particles by at least a factor of 5 to 10. More than 50% of cells which could be demonstrated to be hit by I particles survived and formed colonies."}
{"id": "PMID:217949", "title": "Structural polypeptides of mumps virus.", "content": "The structural polypeptides of egg grown mumps virus were analysed by SDS-polyacrylamide-slab-gel electrophoresis. Mumps virions contained eight major polypeptides with mol. wt. of 75, 73, 71, 61, 47, 44, 42 and 40 X 10(3). The 75 K and 61 K polypeptides were glycosylated. In virions treated with pronase and trypsin, the 75 K glycoprotein was removed more readily from the virus than the 61 K glycoprotein. The gradual removal of the 75 K glycoprotein was paralleled by a decrease of haemagglutinating activity. The large glycoprotein was cleaved into a 40 K glycoprotein by trypsin treatment. Pronase and trypsin treatment also removed the smallest 40 K non-glycosylated polypeptide. Thus this polypeptide appears to be located on the outside of the virion and probably represents a cleavage product of the large glycoprotein. Treatment of virions with 2% Triton-X 100 under alkaline conditions in the absence or presence of 2 M-KCl solubilized the two glycoproteins and a fraction of the 71 and 44 K polypeptides, but not the 73 and 47 K polypeptides. The two smallest polypeptides were solubilized by treatment with 2% Triton X-100 in the presence of 2 M-KCl. Since the 40 K polypeptide was interpreted to represent a cleavage product of the large surface glycoprotein the 42 K polypeptide was proposed to represent the membrane protein of mumps virus. The 44 K polypeptide co-migrated with Vero cell actin. The nature of the 47 K polypeptide could not be determined, but it is probably located in the central part of the virus. The 73 K polypeptide and in some experiments also the 71 K polypeptide were found in purified nucleocapsid preparations. It is concluded that mumps virus has a general polypeptide composition similar to other paramyxoviruses. However, the molecular weights of the different polypeptides of mumps virus differ markedly from the corresponding polypeptides in Newcastle disease virus and Sendai virus.", "contents": "Structural polypeptides of mumps virus. The structural polypeptides of egg grown mumps virus were analysed by SDS-polyacrylamide-slab-gel electrophoresis. Mumps virions contained eight major polypeptides with mol. wt. of 75, 73, 71, 61, 47, 44, 42 and 40 X 10(3). The 75 K and 61 K polypeptides were glycosylated. In virions treated with pronase and trypsin, the 75 K glycoprotein was removed more readily from the virus than the 61 K glycoprotein. The gradual removal of the 75 K glycoprotein was paralleled by a decrease of haemagglutinating activity. The large glycoprotein was cleaved into a 40 K glycoprotein by trypsin treatment. Pronase and trypsin treatment also removed the smallest 40 K non-glycosylated polypeptide. Thus this polypeptide appears to be located on the outside of the virion and probably represents a cleavage product of the large glycoprotein. Treatment of virions with 2% Triton-X 100 under alkaline conditions in the absence or presence of 2 M-KCl solubilized the two glycoproteins and a fraction of the 71 and 44 K polypeptides, but not the 73 and 47 K polypeptides. The two smallest polypeptides were solubilized by treatment with 2% Triton X-100 in the presence of 2 M-KCl. Since the 40 K polypeptide was interpreted to represent a cleavage product of the large surface glycoprotein the 42 K polypeptide was proposed to represent the membrane protein of mumps virus. The 44 K polypeptide co-migrated with Vero cell actin. The nature of the 47 K polypeptide could not be determined, but it is probably located in the central part of the virus. The 73 K polypeptide and in some experiments also the 71 K polypeptide were found in purified nucleocapsid preparations. It is concluded that mumps virus has a general polypeptide composition similar to other paramyxoviruses. However, the molecular weights of the different polypeptides of mumps virus differ markedly from the corresponding polypeptides in Newcastle disease virus and Sendai virus."}
{"id": "PMID:217944", "title": "Structural modification of polyfunctional rubratoxin B: effects on mammalian adenosine triphosphatase.", "content": "Rubratoxin B, an alpha, beta unsaturated lactone containing bisanhydride metabolite of certain toxigenic strains of penicillium molds, significantly inhibited in vitro brain microsomal Na+ - K+ adenosine triphosphatase from swine, mouse, and rat with IC50's of 6.76, 6.67, and 6.80 x 10(-6) M, respectively. Mitochondrial Mg++ oligomycin-sensitive ATPase from mouse liver was also inhibited with an IC50 of 6.30 x 10(-6) M rubratoxin B. Structural modification of the polyfunctional parent compound (rubratoxin B) to rubratoxin A (a gamma lactol replaces one of the anhydride moieties) or formation of the dihydro analogs of rubratoxins A and B (2,3 saturated delta lactone) decreased inhibition to all ATPase systems. The structure-activity relationship relative to ATPase inhibition was rubratoxin B greater than dihydrorubratoxin B greater than rubratoxin A greater than dihydrorubratoxin A. The order of reactivity by these analogs to brain microsomal Na+ -K+ ATPase from 3 mammalian species and to mouse hepatic mitochondrial Mg++ ATPase was similar, indicating no significant species variations. These results suggest that the previously demonstrated in vivo inhibition of adenosine triphosphatase preparations by rubratoxin B was the result of the intact parent compound, because chemical alteration of any one of the functional moieties (either the maleic anhydride ring or conjugated lactone) resulted in significantly decreased inhibition of ATPase activity.", "contents": "Structural modification of polyfunctional rubratoxin B: effects on mammalian adenosine triphosphatase. Rubratoxin B, an alpha, beta unsaturated lactone containing bisanhydride metabolite of certain toxigenic strains of penicillium molds, significantly inhibited in vitro brain microsomal Na+ - K+ adenosine triphosphatase from swine, mouse, and rat with IC50's of 6.76, 6.67, and 6.80 x 10(-6) M, respectively. Mitochondrial Mg++ oligomycin-sensitive ATPase from mouse liver was also inhibited with an IC50 of 6.30 x 10(-6) M rubratoxin B. Structural modification of the polyfunctional parent compound (rubratoxin B) to rubratoxin A (a gamma lactol replaces one of the anhydride moieties) or formation of the dihydro analogs of rubratoxins A and B (2,3 saturated delta lactone) decreased inhibition to all ATPase systems. The structure-activity relationship relative to ATPase inhibition was rubratoxin B greater than dihydrorubratoxin B greater than rubratoxin A greater than dihydrorubratoxin A. The order of reactivity by these analogs to brain microsomal Na+ -K+ ATPase from 3 mammalian species and to mouse hepatic mitochondrial Mg++ ATPase was similar, indicating no significant species variations. These results suggest that the previously demonstrated in vivo inhibition of adenosine triphosphatase preparations by rubratoxin B was the result of the intact parent compound, because chemical alteration of any one of the functional moieties (either the maleic anhydride ring or conjugated lactone) resulted in significantly decreased inhibition of ATPase activity."}
{"id": "PMID:217950", "title": "Effect of ammonium salts on the interferon-induced antiviral state in mouse L cells.", "content": "The addition of ammonium salts to cells treated with interferon prevents the development of the antiviral state and destroys it when already established. This treatment does not seem to act on the binding of interferon to the cells but blocks a further step of activation on the cell membrane. The anti-interferon effect of ammonium salts is reversible with a complete recovery of the antiviral state. It is postulated that these salts may stabilize the interferon-receptor complex and thus prevent the changes in configuration necessary for the establishment and maintenance of its biological functions.", "contents": "Effect of ammonium salts on the interferon-induced antiviral state in mouse L cells. The addition of ammonium salts to cells treated with interferon prevents the development of the antiviral state and destroys it when already established. This treatment does not seem to act on the binding of interferon to the cells but blocks a further step of activation on the cell membrane. The anti-interferon effect of ammonium salts is reversible with a complete recovery of the antiviral state. It is postulated that these salts may stabilize the interferon-receptor complex and thus prevent the changes in configuration necessary for the establishment and maintenance of its biological functions."}
{"id": "PMID:217951", "title": "Neutralization of Mason-Pfizer virus by sera from patients treated for renal disease.", "content": "Sera from 67 patients treated for renal diseases were assayed by as many as three different tests for activities against Mason-Pfizer virus (M-P V) antigens. Firstly, in patients studied before kidney transplantation, neutralizing activity against syncytium-forming units of M-P V was found in 50% of 24 cases of chronic glomerulonephritis but in only 10% of 20 cases with other diseases (P less than 0.01). These proportions were higher after treatments accompanying transplantation since, of the 19 patients without antibodies before graft, 53% showed a sero-conversion after this treatment. The incidence of M-P V antibodies did not correlate with the number of transfusions received by the patients. Neither did these antibodies correlate with the presence of antibodies to antigens associated with baboon endogenous virus or simian sarcoma virus; antibodies to the latter two viruses were found in 6 to 21% of the sera, with no specific distribution among the sera. Secondly, pseudotypes of vesicular stomatitis virus with M-P V antigens in their envelope were prepared; they were inactivated by 90% of the sera which neutralized M-P V syncytium forming units and by none of the negative sera. Thirdly, specific complement-dependent cytotoxic antibodies to HeLa cells producing M-P V were also found in 61% of the sera with neutralizing activity to M-P V and only in 12% of the sera which did not neutralize M-P V. Absorption experiments indicated that the serum activities against M-P V associated antigens were not due to anticellular antibodies directed against normal constituents of human cells. However, no evidence has been provided that the M-P V associated antigens reacting with the human sera were virus coded.", "contents": "Neutralization of Mason-Pfizer virus by sera from patients treated for renal disease. Sera from 67 patients treated for renal diseases were assayed by as many as three different tests for activities against Mason-Pfizer virus (M-P V) antigens. Firstly, in patients studied before kidney transplantation, neutralizing activity against syncytium-forming units of M-P V was found in 50% of 24 cases of chronic glomerulonephritis but in only 10% of 20 cases with other diseases (P less than 0.01). These proportions were higher after treatments accompanying transplantation since, of the 19 patients without antibodies before graft, 53% showed a sero-conversion after this treatment. The incidence of M-P V antibodies did not correlate with the number of transfusions received by the patients. Neither did these antibodies correlate with the presence of antibodies to antigens associated with baboon endogenous virus or simian sarcoma virus; antibodies to the latter two viruses were found in 6 to 21% of the sera, with no specific distribution among the sera. Secondly, pseudotypes of vesicular stomatitis virus with M-P V antigens in their envelope were prepared; they were inactivated by 90% of the sera which neutralized M-P V syncytium forming units and by none of the negative sera. Thirdly, specific complement-dependent cytotoxic antibodies to HeLa cells producing M-P V were also found in 61% of the sera with neutralizing activity to M-P V and only in 12% of the sera which did not neutralize M-P V. Absorption experiments indicated that the serum activities against M-P V associated antigens were not due to anticellular antibodies directed against normal constituents of human cells. However, no evidence has been provided that the M-P V associated antigens reacting with the human sera were virus coded."}
{"id": "PMID:217952", "title": "Circular, circular-linear and branched herpes simplex virus DNA molecules from arginine deprived cells.", "content": "Analysis of the virus DNA isolated from arginine deprived cells revealed that the majority of DNA molecules are linear, with some molecules having one or more short branches. In addition, circular and circular-linear DNA molecules of genome size and smaller were observed.", "contents": "Circular, circular-linear and branched herpes simplex virus DNA molecules from arginine deprived cells. Analysis of the virus DNA isolated from arginine deprived cells revealed that the majority of DNA molecules are linear, with some molecules having one or more short branches. In addition, circular and circular-linear DNA molecules of genome size and smaller were observed."}
{"id": "PMID:217953", "title": "Replication of animal viruses in differentiating muscle cells: vaccinia and herpes simplex virus type 1.", "content": "Cells cultured from the breast muscles of 11 to 12-day-old chick embryos were infected in the undifferentiated mitotic myoblast stage or in the terminally differentiated non-mitotic myotube stage with one of two DNA viruses, vaccinia and herpes simplex virus type 1 (HSV-1). DNA synthesis was measured and production ov virus-specific DNA detected in cells infected as myoblasts or myotubes by isotope labelling, autoradiographic and buoyant density centrifugation techniques. Furthermore, fully fused myotubes resemble myoblasts in their ability to support productive infection by these DNA viruses although DNA replication and nuclear division have ceased in myotubes and only minimum levels of host-cell DNA polymerase activity are present.", "contents": "Replication of animal viruses in differentiating muscle cells: vaccinia and herpes simplex virus type 1. Cells cultured from the breast muscles of 11 to 12-day-old chick embryos were infected in the undifferentiated mitotic myoblast stage or in the terminally differentiated non-mitotic myotube stage with one of two DNA viruses, vaccinia and herpes simplex virus type 1 (HSV-1). DNA synthesis was measured and production ov virus-specific DNA detected in cells infected as myoblasts or myotubes by isotope labelling, autoradiographic and buoyant density centrifugation techniques. Furthermore, fully fused myotubes resemble myoblasts in their ability to support productive infection by these DNA viruses although DNA replication and nuclear division have ceased in myotubes and only minimum levels of host-cell DNA polymerase activity are present."}
{"id": "PMID:217954", "title": "Protease activation of Sendai virus infectivity; studies in non-permissive and permissive cells.", "content": "Non-infectious virus particles are produced by BSC-1 cells after infection with Sendai virus. Trypsin treatment of these particles activates their infectivity. The studies reported here show that such non-infectious virus particles adsorb normally to cells but cannot initiate infection even after very long adsorption periods. Secondary Rhesus monkey kidney cells support the growth of Sendai virus but cannot activate the infectivity of virus grown in BSC-1 cells. The significance of these results is discussed.", "contents": "Protease activation of Sendai virus infectivity; studies in non-permissive and permissive cells. Non-infectious virus particles are produced by BSC-1 cells after infection with Sendai virus. Trypsin treatment of these particles activates their infectivity. The studies reported here show that such non-infectious virus particles adsorb normally to cells but cannot initiate infection even after very long adsorption periods. Secondary Rhesus monkey kidney cells support the growth of Sendai virus but cannot activate the infectivity of virus grown in BSC-1 cells. The significance of these results is discussed."}
{"id": "PMID:217955", "title": "Decreased production of transforming virus and altered antigenic behaviour in cultured avian sarcoma cells.", "content": "Tumours induced in chickens by inoculation of avian sarcoma viruses are frequently capable of undergoing spontaneous regression. It is only those tumour cells which have been derived from progressively growing neoplasms that are able to produce transforming progeny virus in vitro and to shed into the culture medium antigens which are specifically reactive with the peripheral lymphocytes of sarcoma-bearing hosts. Following multiple passages and extended growth in culture, however, the ability of these tumour cell fluids to stimulate the lymphocytes of sensitized hosts diminishes in concert with the declining capacity of these cells to continue to synthesize fully transforming progeny virus. In certain instances, however, aged tumour cells are able to synthesize particles which contain the enzyme RNA-dependent DNA polymerase yet lack detectable envelope glycoprotein.", "contents": "Decreased production of transforming virus and altered antigenic behaviour in cultured avian sarcoma cells. Tumours induced in chickens by inoculation of avian sarcoma viruses are frequently capable of undergoing spontaneous regression. It is only those tumour cells which have been derived from progressively growing neoplasms that are able to produce transforming progeny virus in vitro and to shed into the culture medium antigens which are specifically reactive with the peripheral lymphocytes of sarcoma-bearing hosts. Following multiple passages and extended growth in culture, however, the ability of these tumour cell fluids to stimulate the lymphocytes of sensitized hosts diminishes in concert with the declining capacity of these cells to continue to synthesize fully transforming progeny virus. In certain instances, however, aged tumour cells are able to synthesize particles which contain the enzyme RNA-dependent DNA polymerase yet lack detectable envelope glycoprotein."}
{"id": "PMID:217956", "title": "Stimulation of ornithine decarboxylase by human cytomegalovirus.", "content": "Human cytomegalovirus (HCMV) infection of low serum-arrested confluent whole human embryo (Flow 5000) cells markedly stimulated ornithine decarboxylase (ODC) activity. Increased ODC activity was apparent by 12 h post-infection. The capacity of HCMV to stimulate ODC was: (1) dependent upon multiplicity of infection; (2) eliminated when the virus was neutralized with specific antiserum; and (3) sensitive to ultraviolet irradiation. Virus-mediated induction, in contrast to high serum induction of ODC, was not subject to inhibition by polyamines added to the growth medium. Phosphonoacetic acid (PAA) which blocks HCMV replication by inhibiting the activity of HCMV-specific DNA polymerase and which does not prevent HCMV induced stimulation of cell DNA synthesis, reversibly inhibited HCMV-induced stimulation of ODC activity by 74%. Studies with PAA indicated that HCMV-induced stimulation of ODC activity is independent of cell DNA synthesis and that the mechanism regulating virus-induced stimulation may be related to the HCMV-specific DNA polymerase.", "contents": "Stimulation of ornithine decarboxylase by human cytomegalovirus. Human cytomegalovirus (HCMV) infection of low serum-arrested confluent whole human embryo (Flow 5000) cells markedly stimulated ornithine decarboxylase (ODC) activity. Increased ODC activity was apparent by 12 h post-infection. The capacity of HCMV to stimulate ODC was: (1) dependent upon multiplicity of infection; (2) eliminated when the virus was neutralized with specific antiserum; and (3) sensitive to ultraviolet irradiation. Virus-mediated induction, in contrast to high serum induction of ODC, was not subject to inhibition by polyamines added to the growth medium. Phosphonoacetic acid (PAA) which blocks HCMV replication by inhibiting the activity of HCMV-specific DNA polymerase and which does not prevent HCMV induced stimulation of cell DNA synthesis, reversibly inhibited HCMV-induced stimulation of ODC activity by 74%. Studies with PAA indicated that HCMV-induced stimulation of ODC activity is independent of cell DNA synthesis and that the mechanism regulating virus-induced stimulation may be related to the HCMV-specific DNA polymerase."}
{"id": "PMID:217957", "title": "The neutralization of transmissible gastroenteritis virus by normal heterotypic serum.", "content": "Exposure of transmissible gastroenteritis virus of pigs to unheated normal heterotypic serum resulted in a drop in infectivity, an effect which was lost after heating the serum to 56 degrees C for 30 min or by treatments inactivating complement. Analysis of virus proteins, RNA and lipids, and centrifugation studies showed little difference between inactivated and control virus, but electron microscopy of negatively stained particles after treatment with serum revealed holes in the virus envelope, characteristic of those caused by complement in the presence of antibody.", "contents": "The neutralization of transmissible gastroenteritis virus by normal heterotypic serum. Exposure of transmissible gastroenteritis virus of pigs to unheated normal heterotypic serum resulted in a drop in infectivity, an effect which was lost after heating the serum to 56 degrees C for 30 min or by treatments inactivating complement. Analysis of virus proteins, RNA and lipids, and centrifugation studies showed little difference between inactivated and control virus, but electron microscopy of negatively stained particles after treatment with serum revealed holes in the virus envelope, characteristic of those caused by complement in the presence of antibody."}
{"id": "PMID:217958", "title": "Establishment and characterization of Indian muntjak cell lines transformed with simian virus 40.", "content": "Kidney cells of an Indian muntjak were transformed with simian virus 40 (SV40). The transformation efficiency of the tertiary cultures was very high when estimated by the agar suspension culture method. The efficiency was about 0.015% when infected at an input multiplicity of 0.4 p.f.u./cell. Clonal cell lines were established from the colonies in soft agar medium. Most of the cell lines and their subclones produced a small amount of infectious SV40. The SV40 virion antigen-positive cells in a clone increased from 0.2% to about 40% by the treatment with mitomycin C. More than 70% of the cells in two cell lines were normal in G- and C-banded karyotypes, indicating that chromosomal change is not a necessary step in the process of transformation of the Indian muntjak cells with SV40.", "contents": "Establishment and characterization of Indian muntjak cell lines transformed with simian virus 40. Kidney cells of an Indian muntjak were transformed with simian virus 40 (SV40). The transformation efficiency of the tertiary cultures was very high when estimated by the agar suspension culture method. The efficiency was about 0.015% when infected at an input multiplicity of 0.4 p.f.u./cell. Clonal cell lines were established from the colonies in soft agar medium. Most of the cell lines and their subclones produced a small amount of infectious SV40. The SV40 virion antigen-positive cells in a clone increased from 0.2% to about 40% by the treatment with mitomycin C. More than 70% of the cells in two cell lines were normal in G- and C-banded karyotypes, indicating that chromosomal change is not a necessary step in the process of transformation of the Indian muntjak cells with SV40."}
{"id": "PMID:217959", "title": "Enhancement of infectivity of encephalomyocarditis virus RNA by amphotericin B methyl ester.", "content": "The methyl ester of amphotericin B (AmBME), a macrolide polyene antibiotic, enhanced the infectivity of encephalomyocarditis (EMC) virus RNA for L929 cells. AmBME alone (100 microgram/ml) resulted in increases in EMC virus RNA infectivity of 10- to 100-fold. Addition of DEAE dextran at concentrations (5 microgram/ml), which alone slightly suppressed EMC virus RNA infectivity, further augmented the effects of AmBME (augmentation in infectivity up to 750-fold). AmBME did not inhibit RNase, did not enhance EMC virus infectivity and increased infectivity of EMC virus RNA which was already cell-associated. The polyenes are probably acting by increasing intracellular penetration of polyribonucleotides.", "contents": "Enhancement of infectivity of encephalomyocarditis virus RNA by amphotericin B methyl ester. The methyl ester of amphotericin B (AmBME), a macrolide polyene antibiotic, enhanced the infectivity of encephalomyocarditis (EMC) virus RNA for L929 cells. AmBME alone (100 microgram/ml) resulted in increases in EMC virus RNA infectivity of 10- to 100-fold. Addition of DEAE dextran at concentrations (5 microgram/ml), which alone slightly suppressed EMC virus RNA infectivity, further augmented the effects of AmBME (augmentation in infectivity up to 750-fold). AmBME did not inhibit RNase, did not enhance EMC virus infectivity and increased infectivity of EMC virus RNA which was already cell-associated. The polyenes are probably acting by increasing intracellular penetration of polyribonucleotides."}
{"id": "PMID:217960", "title": "Transformation of rat cells by the hybrid virus Ad2(2+) HEY.", "content": "A set of four isogenic rat cell lines transformed by Ad22+ HEY have been studied. While all of the cell lines synthesize SV40 T antigen, only one expresses adenovirus 2 T antigen: none expresses SV40 V antigen or adenovirus 2 fibre antigen. Three cell lines contain 1 to 2 virus equivalents of SV40 and adenoviral sequences per diploid quantity of rate cell DNA and the fourth line contains five copies of SV40 and 20 copies of the adenovirus genome. At least three of the cell lines contain DNA sequences from the helper adenovirus 2 in addition to sequences from the Ad2+ HEY genome. The patterns of integrated virus sequences are complex suggesting multiple insertions of both adenovirus and SV40 DNA sequences. SV40 can be rescued from three cell lines by fusion with permissive cells.", "contents": "Transformation of rat cells by the hybrid virus Ad2(2+) HEY. A set of four isogenic rat cell lines transformed by Ad22+ HEY have been studied. While all of the cell lines synthesize SV40 T antigen, only one expresses adenovirus 2 T antigen: none expresses SV40 V antigen or adenovirus 2 fibre antigen. Three cell lines contain 1 to 2 virus equivalents of SV40 and adenoviral sequences per diploid quantity of rate cell DNA and the fourth line contains five copies of SV40 and 20 copies of the adenovirus genome. At least three of the cell lines contain DNA sequences from the helper adenovirus 2 in addition to sequences from the Ad2+ HEY genome. The patterns of integrated virus sequences are complex suggesting multiple insertions of both adenovirus and SV40 DNA sequences. SV40 can be rescued from three cell lines by fusion with permissive cells."}
{"id": "PMID:217961", "title": "Mechanisms of interferon induced transfer of viral resistance between animal cells.", "content": "The sequence of events initiated by interferon and leading to the antiviral state were studied as possible sites for the cell-to-cell transfer of interferon induced viral resistance. The possible role of interferon produced by recipient cells was negated by the demonstration of transfer of resistance in the presence of anti-human interferon antibody and under conditions of a single cycle of VSV growth. Transfer of sensitivity of WISH cells to mouse interferon, possibly through transfer of a membrane receptor, seems unlikely since resistance was transferred in the absence of mouse interferon. From kinetic data and the fact that actinomycin D blocked resistance in human cells for 3 h longer than in mouse cells, it seems unlikely that the mouse antiviral protein itself or its mRNA alone is a likely candidate for the transfer of resistance. Thus, by a process of elimination, we suggest that secondary messenger molecules which transmit the interferon signal from the membrane to the nucleus are the effector substance(s) for the transfer process.", "contents": "Mechanisms of interferon induced transfer of viral resistance between animal cells. The sequence of events initiated by interferon and leading to the antiviral state were studied as possible sites for the cell-to-cell transfer of interferon induced viral resistance. The possible role of interferon produced by recipient cells was negated by the demonstration of transfer of resistance in the presence of anti-human interferon antibody and under conditions of a single cycle of VSV growth. Transfer of sensitivity of WISH cells to mouse interferon, possibly through transfer of a membrane receptor, seems unlikely since resistance was transferred in the absence of mouse interferon. From kinetic data and the fact that actinomycin D blocked resistance in human cells for 3 h longer than in mouse cells, it seems unlikely that the mouse antiviral protein itself or its mRNA alone is a likely candidate for the transfer of resistance. Thus, by a process of elimination, we suggest that secondary messenger molecules which transmit the interferon signal from the membrane to the nucleus are the effector substance(s) for the transfer process."}
{"id": "PMID:217962", "title": "Variant lines of mouse kidney cells transformed by an SV40tsA mutant with growth properties of wild-type transformed cells at nonpermissive temperature.", "content": "MKSA207 cells, a BALB/c mouse kidney line transformed by a tsA mutant of SV40, are temperature-dependent for the expression of the 'standard transformed phenotype'. At the permissive temperature (33.5 degrees C), the mKSA207 cells resembled wild-type (wt) SV40 transformants; they contained the intranuclear SV40 T antigen, grew to high saturation density in monolayer culture in either 10% or 0.5% serum, and also in methylcellulose suspension culture and became multinucleate in cytochalasin B. At the nonpermissive temperature (39.8 degrees C), the mKSA207 cells lost some of their transformed properties; they grew only to low density in 10% serum, hardly grew at all in 0.5% serum or in methylcellulose suspension culture, and remained mono- or binucleate in cytochalasin B. At 40 degrees C in low serum, mKSA207 cells lost the intranuclear T antigen and when fed 10% serum at 39.8 degrees C, accumulated large amounts of T antigen in the cytoplasm. Derivatives of mKSA207 have been selected at 39.8 degrees C in liquid medium and methylcellulose suspension culture. The heat adapted lines, like wt SV40 transformants, exhibited the standard transformed phenotype at both 33.5 and 39.8 degrees C. It is unlikely that acquisition of temperature-independence for the transformed phenotype was due to reversion of the tsA gene to wild-type because the heat-adapted cell lines displayed the cytoplasmic T antigen at 39.8 degrees C, characteristic of the parental mKSA207 cells and SV40 rescued from one of the heat-adapted lines was temperature sensitive for growth. The T antigen levels (complement fixation units per 10(6) cells) of heat-adapted lines grown at 39.8 degrees C were comparable to those of mKSA207 cells grown at 33.5 or 39.8 degrees C.", "contents": "Variant lines of mouse kidney cells transformed by an SV40tsA mutant with growth properties of wild-type transformed cells at nonpermissive temperature. MKSA207 cells, a BALB/c mouse kidney line transformed by a tsA mutant of SV40, are temperature-dependent for the expression of the 'standard transformed phenotype'. At the permissive temperature (33.5 degrees C), the mKSA207 cells resembled wild-type (wt) SV40 transformants; they contained the intranuclear SV40 T antigen, grew to high saturation density in monolayer culture in either 10% or 0.5% serum, and also in methylcellulose suspension culture and became multinucleate in cytochalasin B. At the nonpermissive temperature (39.8 degrees C), the mKSA207 cells lost some of their transformed properties; they grew only to low density in 10% serum, hardly grew at all in 0.5% serum or in methylcellulose suspension culture, and remained mono- or binucleate in cytochalasin B. At 40 degrees C in low serum, mKSA207 cells lost the intranuclear T antigen and when fed 10% serum at 39.8 degrees C, accumulated large amounts of T antigen in the cytoplasm. Derivatives of mKSA207 have been selected at 39.8 degrees C in liquid medium and methylcellulose suspension culture. The heat adapted lines, like wt SV40 transformants, exhibited the standard transformed phenotype at both 33.5 and 39.8 degrees C. It is unlikely that acquisition of temperature-independence for the transformed phenotype was due to reversion of the tsA gene to wild-type because the heat-adapted cell lines displayed the cytoplasmic T antigen at 39.8 degrees C, characteristic of the parental mKSA207 cells and SV40 rescued from one of the heat-adapted lines was temperature sensitive for growth. The T antigen levels (complement fixation units per 10(6) cells) of heat-adapted lines grown at 39.8 degrees C were comparable to those of mKSA207 cells grown at 33.5 or 39.8 degrees C."}
{"id": "PMID:217963", "title": "Type C virus induced by iododeoxyuridine in the human embryonic cell strain HEL-12.", "content": "The induction of a type C virus from a strain of human embryonic lung cells (HEL-12) by iododeoxyuridine (IdUrd) was examined at various times during in vitro propagation. IdUrd did not elicit type C virus production immediately following initiation of cultures from frozen primary HEL-12 cells. After overnight treatment with 30 microgram/ml IdUrd the cells expressed viral antigens and produced a type  C virus between the 25th and 80th day of in vitro growth. Production of the induced type C virus was transient. Single-cell clones of the parental HEL-12 strain were likewise susceptible to type C virus production by IdUrd. The ability of IdUrd to induce virus terminated with the onset of spontaneous type C virus production from HEL-12 cells at between 80 and 120 days of in vitro growth.", "contents": "Type C virus induced by iododeoxyuridine in the human embryonic cell strain HEL-12. The induction of a type C virus from a strain of human embryonic lung cells (HEL-12) by iododeoxyuridine (IdUrd) was examined at various times during in vitro propagation. IdUrd did not elicit type C virus production immediately following initiation of cultures from frozen primary HEL-12 cells. After overnight treatment with 30 microgram/ml IdUrd the cells expressed viral antigens and produced a type  C virus between the 25th and 80th day of in vitro growth. Production of the induced type C virus was transient. Single-cell clones of the parental HEL-12 strain were likewise susceptible to type C virus production by IdUrd. The ability of IdUrd to induce virus terminated with the onset of spontaneous type C virus production from HEL-12 cells at between 80 and 120 days of in vitro growth."}
{"id": "PMID:217964", "title": "Differentiation between SV40 large-T and U antigenic sites.", "content": "Radioimmune precipitation, SDS-polyacrylamide slab gel electrophoresis and fluorography were used to investigate the SV40 large-T and U antigenic sites on species of proteins synthesized during wild type and tsA58 mutant infections in TC7 monkey cells. Wild type infection at 33 and 41.5 degrees C and the A58 infection at 33 degrees C produced similar profiles of three species ranging in mol. wt. from 84000 to 94000, all of which had both the large-T and U antigenic sites. The A58 infection at 41.5 degrees C, however, produced an additional four discrete species ranging in mol. wt. from 60000 to 74000 that contained the large-T site(s), but not the U site(s). A subpopulation of the 74000 mol. wt. species contained both sites. Therefore, the region of the A58 mutant 94000 mol. wt. species containing the U antigenic site(s), the COOH-terminal region, appears to be more sensitive to processing, probably proteolytic cleavage, than does the region containing the large-T antigenic site(s).", "contents": "Differentiation between SV40 large-T and U antigenic sites. Radioimmune precipitation, SDS-polyacrylamide slab gel electrophoresis and fluorography were used to investigate the SV40 large-T and U antigenic sites on species of proteins synthesized during wild type and tsA58 mutant infections in TC7 monkey cells. Wild type infection at 33 and 41.5 degrees C and the A58 infection at 33 degrees C produced similar profiles of three species ranging in mol. wt. from 84000 to 94000, all of which had both the large-T and U antigenic sites. The A58 infection at 41.5 degrees C, however, produced an additional four discrete species ranging in mol. wt. from 60000 to 74000 that contained the large-T site(s), but not the U site(s). A subpopulation of the 74000 mol. wt. species contained both sites. Therefore, the region of the A58 mutant 94000 mol. wt. species containing the U antigenic site(s), the COOH-terminal region, appears to be more sensitive to processing, probably proteolytic cleavage, than does the region containing the large-T antigenic site(s)."}
{"id": "PMID:217965", "title": "SV40-transformed human diploid cells that remain transformed throughout their limited lifespan.", "content": "Of ninety-one subcultured foci of SV40-transformed WI-38 human diploid fibroblasts, none yielded cells that grew indefinitely, but all cells in each subculture continued to produce T antigen and to look morphologically transformed throughout their lifespan. These results are consistent with the commitment theory of fibroblast senescence, but predict that a special transformation event is necessary to accout for the rare survivors.", "contents": "SV40-transformed human diploid cells that remain transformed throughout their limited lifespan. Of ninety-one subcultured foci of SV40-transformed WI-38 human diploid fibroblasts, none yielded cells that grew indefinitely, but all cells in each subculture continued to produce T antigen and to look morphologically transformed throughout their lifespan. These results are consistent with the commitment theory of fibroblast senescence, but predict that a special transformation event is necessary to accout for the rare survivors."}
{"id": "PMID:217966", "title": "Inhibition of a complete replication cycle of human cytomegalovirus in actinomycin pre-treated cells.", "content": "The study of human cytomegalovirus (HCMV) in cultures of human embryo lung fibroblasts, pre-treated with actinomycin D, has shown that under these conditions the virus infection does not proceed beyond the 'early' events of the virus replication cycle. In the same experimental conditions the growth of poliovirus type I, vaccinia virus and herpes simplex type I virus, was completely unaffected. These results suggest that the complete HCMV replication cycle requires some cellular function(s) between early transcription of the input virus genome and virus DNA synthesis.", "contents": "Inhibition of a complete replication cycle of human cytomegalovirus in actinomycin pre-treated cells. The study of human cytomegalovirus (HCMV) in cultures of human embryo lung fibroblasts, pre-treated with actinomycin D, has shown that under these conditions the virus infection does not proceed beyond the 'early' events of the virus replication cycle. In the same experimental conditions the growth of poliovirus type I, vaccinia virus and herpes simplex type I virus, was completely unaffected. These results suggest that the complete HCMV replication cycle requires some cellular function(s) between early transcription of the input virus genome and virus DNA synthesis."}
{"id": "PMID:217967", "title": "Studies on polyoma virus DNA replication in synchronized C3H2K cells.", "content": "In G1-arrested cells infected between 1 and 12 h after having been stimulated by fresh serum to progress to S phase, polyoma virus DNA synthesis proceeded in the first half of S phase, and virus and whole cellular DNA accumulated at about the same time. However, in cells infected later than 14 h after serum stimulation, virus DNA synthesis was shifted to the next S phase. Thus, a permissive cell attains competence for polyoma virus DNA replication at a precise moment during an S phase initiated by fresh serum, which can efficiently replace the early virus host DNA stimulation function. When cells were incubated in serum that had lost its capacity to stimulate host DNA synthesis by pre-absorption with growing cells, normal yields of polyoma DNA could nevertheless be observed, which shows that extensive replication of host DNA does not seem to be an obligatory condition for virus DNA replication.", "contents": "Studies on polyoma virus DNA replication in synchronized C3H2K cells. In G1-arrested cells infected between 1 and 12 h after having been stimulated by fresh serum to progress to S phase, polyoma virus DNA synthesis proceeded in the first half of S phase, and virus and whole cellular DNA accumulated at about the same time. However, in cells infected later than 14 h after serum stimulation, virus DNA synthesis was shifted to the next S phase. Thus, a permissive cell attains competence for polyoma virus DNA replication at a precise moment during an S phase initiated by fresh serum, which can efficiently replace the early virus host DNA stimulation function. When cells were incubated in serum that had lost its capacity to stimulate host DNA synthesis by pre-absorption with growing cells, normal yields of polyoma DNA could nevertheless be observed, which shows that extensive replication of host DNA does not seem to be an obligatory condition for virus DNA replication."}
{"id": "PMID:217968", "title": "The effect of 1-beta-D-arabinofuranosylthymine on the growth of herpes simplex virus types 1 and 2.", "content": "The influence of araT on the synthesis of HSV of types 1 and 2 including a TK(--) variant, on the activity  of the dThd and the dCyd kinases and on the incorporation of radioactivity into insoluble or soluble material after infection was studied. AraT inhibited different parameters of the replication of a TK(--) variant; it is possibly phosphorylated by enzymes other than the deoxypyrimidine kinase and therefore it is less selectively phosphorylated than dThd. The mode of action of araT on herpes replication must be studied in more detail.", "contents": "The effect of 1-beta-D-arabinofuranosylthymine on the growth of herpes simplex virus types 1 and 2. The influence of araT on the synthesis of HSV of types 1 and 2 including a TK(--) variant, on the activity  of the dThd and the dCyd kinases and on the incorporation of radioactivity into insoluble or soluble material after infection was studied. AraT inhibited different parameters of the replication of a TK(--) variant; it is possibly phosphorylated by enzymes other than the deoxypyrimidine kinase and therefore it is less selectively phosphorylated than dThd. The mode of action of araT on herpes replication must be studied in more detail."}
{"id": "PMID:217969", "title": "Mengovirus-induced capping of virus receptors on the plasma membrane of Ehrlich ascites tumour cells.", "content": "Mengovirus particles adsorbed to Ehrlich ascites tumour cells are redistributed into patches and caps without the action of antibodies. Thus capping may be an early signal in picornavirus infection.", "contents": "Mengovirus-induced capping of virus receptors on the plasma membrane of Ehrlich ascites tumour cells. Mengovirus particles adsorbed to Ehrlich ascites tumour cells are redistributed into patches and caps without the action of antibodies. Thus capping may be an early signal in picornavirus infection."}
{"id": "PMID:217970", "title": "Transcranial management of pituitary tumours with suprasellar extension.", "content": "A consecutive series of 101 pituitary tumours treated in the 10 year period 1968-78 has been examined, giant lesions being excluded. There were 48 female cases and 53 male, women predominating in the ratio of three to two in the age group 40-50 years and men showing a slight predominance in the age group 50-60 years. Most cases presented with visual deterioration which in 22 cases had been present for between one and two years, and in a further 22 for an even longer period, between two and 10 years. All patients underwent subfrontal craniotomy with mainly radical excision of the tumour followed by radiotherapy. The operative mortality was 0.99%. A system of grading of visual field defect has been described and used to compare preoperatively visual loss with postoperative visual recovery. Fifty-six per cent of cases returned to normal vision over the first two years, and a further 37% showed appreciable improvement in visual fields or acuity or both. Six per cent of cases showed no improvement in visual fields, and one patient died of postoperative deep vein thrombosis and pulmonary embolism. The degree of visual improvement has been correlated with the extent of visual defect, length of visual complaint, and size of the tumour. The importance of central and peripheral visual field analysis is emphasised yet again.", "contents": "Transcranial management of pituitary tumours with suprasellar extension. A consecutive series of 101 pituitary tumours treated in the 10 year period 1968-78 has been examined, giant lesions being excluded. There were 48 female cases and 53 male, women predominating in the ratio of three to two in the age group 40-50 years and men showing a slight predominance in the age group 50-60 years. Most cases presented with visual deterioration which in 22 cases had been present for between one and two years, and in a further 22 for an even longer period, between two and 10 years. All patients underwent subfrontal craniotomy with mainly radical excision of the tumour followed by radiotherapy. The operative mortality was 0.99%. A system of grading of visual field defect has been described and used to compare preoperatively visual loss with postoperative visual recovery. Fifty-six per cent of cases returned to normal vision over the first two years, and a further 37% showed appreciable improvement in visual fields or acuity or both. Six per cent of cases showed no improvement in visual fields, and one patient died of postoperative deep vein thrombosis and pulmonary embolism. The degree of visual improvement has been correlated with the extent of visual defect, length of visual complaint, and size of the tumour. The importance of central and peripheral visual field analysis is emphasised yet again."}
{"id": "PMID:217971", "title": "Significance of immunoglobulin deposition in peripheral nerve in neuropathies associated with paraproteinaemia.", "content": "Direct and indirect immunofluorescent studies of sural nerves were carried out in two patients with paraproteinaemia and neuropathy, in four other patients with axonal or demyelinating neuropathies, and in one normal sural nerve. IgM was demonstrated directly in the two cases of paraproteinaemia and neuropathy, and indirectly, using the serum of one of these cases, in a case of axonal neuropathy and in one case of chronic Guillain-Barr\u00e9 syndrome. In the latter case, IgM deposition also occurred after exposure to normal serum. These results suggest that the paraprotein itself did not directly cause neuropathy, but that immunoglobulin deposition is probably a secondary process, caused by diffusion into damaged nerves.", "contents": "Significance of immunoglobulin deposition in peripheral nerve in neuropathies associated with paraproteinaemia. Direct and indirect immunofluorescent studies of sural nerves were carried out in two patients with paraproteinaemia and neuropathy, in four other patients with axonal or demyelinating neuropathies, and in one normal sural nerve. IgM was demonstrated directly in the two cases of paraproteinaemia and neuropathy, and indirectly, using the serum of one of these cases, in a case of axonal neuropathy and in one case of chronic Guillain-Barr\u00e9 syndrome. In the latter case, IgM deposition also occurred after exposure to normal serum. These results suggest that the paraprotein itself did not directly cause neuropathy, but that immunoglobulin deposition is probably a secondary process, caused by diffusion into damaged nerves."}
{"id": "PMID:217972", "title": "Electrotonic coupling among neuroendocrine cells in Aplysia.", "content": "1. We have discovered and characterized direct electrotonic synaptic coupling among a population of neuroendocrine (bag) cells in the parietovisceral ganglion of the marine gastropod Aplysia dactylomela. Pairs of ipsilateral and contralateral bag cells were impaled in vitro with microelectrodes. Current pulses applied through the electrometer amplifier to either cell influenced the other cell via electrotonic connections. 2. The coupling between bag cells was relatively weak when measured at the somata; the mean ratio of postsynaptic/presynaptic response amplitudes is 0.0075. Junctional rectification was not detected. The latency between pre- and postjunctional responses was long, up to 50 ms, a delay comparable to that for chemical synaptic transmission among neurons in this ganglion. Low-Ca2+/high-Mg2+ bathing solutions did not block transmission between bag cells, but did block chemical synaptic potentials in other identified neurons. 3. Postjunctional electrotonic responses had markedly slow time courses compared to the prejunctional responses, a characteristic that permitted summation of otherwise undetectable electrotonic PSPs and the demonstration of coupling between the two (bilateral) clusters of bag cells. 4. Based on extracellular recordings of their compound action potentials, the neurites of A. dactylomela bag cells extended a shorter distance (approximately 3 mm) along the connective than the neurites of A. californica or A. brasiliana. 5. Electrolytic lesions made along the neurites during intrasomatic coupling measurements significantly shortened the duration of postjuctional electrotonic responses, indicating that the neurites are widely electrically interconnected and, as a population, have a large effective membrane capacitance. The lesions furthermore revealed that an important site of electrotonic coupling is at the base of the pleurovisceral connective just rostral to the bag cell cluster. 6. The small-amplitude, long-latency and prolonged time course of postjunctional responses are interpreted to indicate remote and widespread coupling sites among the bag cells. This electrotonic coupling underlies the synchronized firing of the bag cells.", "contents": "Electrotonic coupling among neuroendocrine cells in Aplysia. 1. We have discovered and characterized direct electrotonic synaptic coupling among a population of neuroendocrine (bag) cells in the parietovisceral ganglion of the marine gastropod Aplysia dactylomela. Pairs of ipsilateral and contralateral bag cells were impaled in vitro with microelectrodes. Current pulses applied through the electrometer amplifier to either cell influenced the other cell via electrotonic connections. 2. The coupling between bag cells was relatively weak when measured at the somata; the mean ratio of postsynaptic/presynaptic response amplitudes is 0.0075. Junctional rectification was not detected. The latency between pre- and postjunctional responses was long, up to 50 ms, a delay comparable to that for chemical synaptic transmission among neurons in this ganglion. Low-Ca2+/high-Mg2+ bathing solutions did not block transmission between bag cells, but did block chemical synaptic potentials in other identified neurons. 3. Postjunctional electrotonic responses had markedly slow time courses compared to the prejunctional responses, a characteristic that permitted summation of otherwise undetectable electrotonic PSPs and the demonstration of coupling between the two (bilateral) clusters of bag cells. 4. Based on extracellular recordings of their compound action potentials, the neurites of A. dactylomela bag cells extended a shorter distance (approximately 3 mm) along the connective than the neurites of A. californica or A. brasiliana. 5. Electrolytic lesions made along the neurites during intrasomatic coupling measurements significantly shortened the duration of postjuctional electrotonic responses, indicating that the neurites are widely electrically interconnected and, as a population, have a large effective membrane capacitance. The lesions furthermore revealed that an important site of electrotonic coupling is at the base of the pleurovisceral connective just rostral to the bag cell cluster. 6. The small-amplitude, long-latency and prolonged time course of postjunctional responses are interpreted to indicate remote and widespread coupling sites among the bag cells. This electrotonic coupling underlies the synchronized firing of the bag cells."}
{"id": "PMID:217973", "title": "Interactions between bilateral clusters of neuroendocrine cells in Aplysia.", "content": "1. Activity of bilateral clusters of electrotonically coupled neuroendocrine cells (the bag cells) was studied using multiple-site intracellular and extracellular recording techniques in isolated parietovisceral ganglia of three species of Aplysia. Bilateral afterdischarges typically began with spike initiation on one side near the neurite terminals along the pleurovisceral connective; propagation of action potentials then proceeded toward the somata with potentiation to full somatic invasion in the ipsilateral bag cell cluster. This activity potentiated across the parietovisceral ganglion until contralateral spikes were initiated at a point near the bag cell somata (designated site A) and compound bag cell activity was then propagated both inward toward the somata and outward toward the circumesophageal ring of head ganglia. This sequence of events, i.e., \"in one side, out the other,\" could occur several times during an afterdischarge, although outward propagation of activity was rarely maintained for more than 20 spikes. Synchrony between clusters was best during these periods of activity. Usually after a few episodes of this sequence, the sites of spike initiation spontaneously shifted to near the neurite terminals of each side and activity was initiated distally and propagated inward. Asychrony between clusters commonly developed when the sites for spike initiation were near the neurite terminals of each side. 2. Waveforms and temporal sequence of recorded events indicate that at least two sites for spike initiation exist within the neuritic tree of each bag cell cluster. These are the distal terminations of the neurites and a proximal site near the somata. Action potentials could be generated at this proximal site spontaneously or when electrotonically driven by contralateral activity. Removal of the bag cell somata did not interfere with bilateral behavior of the bag cell system. The proximal site is, therefore, not somatic. Activity initiated there was always more synchronous and propagated with a higher conduction velocity than activity initiated at the distal ends of the neurites. 3. Experiments were performed with and without the circumesophageal ring of head ganglia intact. Removal of the head ganglia had no effect on bilaterality of or synchrony within the bag cell system. Systematic stimulations and cuts of head ring connectives suggested that the cerebral ganglion may participate in orthodromic activation of the bag cells. 4. Our findings indicate the bag cells of Aplysia are a homogeneous population of neuroendocrine cells with multiple sites for spike initiation. Either cluster can serve as a pacemaker for the other through potentiation and electrotonic activation of the contralateral cluster at proximal sites on the neurites.", "contents": "Interactions between bilateral clusters of neuroendocrine cells in Aplysia. 1. Activity of bilateral clusters of electrotonically coupled neuroendocrine cells (the bag cells) was studied using multiple-site intracellular and extracellular recording techniques in isolated parietovisceral ganglia of three species of Aplysia. Bilateral afterdischarges typically began with spike initiation on one side near the neurite terminals along the pleurovisceral connective; propagation of action potentials then proceeded toward the somata with potentiation to full somatic invasion in the ipsilateral bag cell cluster. This activity potentiated across the parietovisceral ganglion until contralateral spikes were initiated at a point near the bag cell somata (designated site A) and compound bag cell activity was then propagated both inward toward the somata and outward toward the circumesophageal ring of head ganglia. This sequence of events, i.e., \"in one side, out the other,\" could occur several times during an afterdischarge, although outward propagation of activity was rarely maintained for more than 20 spikes. Synchrony between clusters was best during these periods of activity. Usually after a few episodes of this sequence, the sites of spike initiation spontaneously shifted to near the neurite terminals of each side and activity was initiated distally and propagated inward. Asychrony between clusters commonly developed when the sites for spike initiation were near the neurite terminals of each side. 2. Waveforms and temporal sequence of recorded events indicate that at least two sites for spike initiation exist within the neuritic tree of each bag cell cluster. These are the distal terminations of the neurites and a proximal site near the somata. Action potentials could be generated at this proximal site spontaneously or when electrotonically driven by contralateral activity. Removal of the bag cell somata did not interfere with bilateral behavior of the bag cell system. The proximal site is, therefore, not somatic. Activity initiated there was always more synchronous and propagated with a higher conduction velocity than activity initiated at the distal ends of the neurites. 3. Experiments were performed with and without the circumesophageal ring of head ganglia intact. Removal of the head ganglia had no effect on bilaterality of or synchrony within the bag cell system. Systematic stimulations and cuts of head ring connectives suggested that the cerebral ganglion may participate in orthodromic activation of the bag cells. 4. Our findings indicate the bag cells of Aplysia are a homogeneous population of neuroendocrine cells with multiple sites for spike initiation. Either cluster can serve as a pacemaker for the other through potentiation and electrotonic activation of the contralateral cluster at proximal sites on the neurites."}
{"id": "PMID:217974", "title": "Central and peripheral control of siphon-withdrawal reflex in Aplysia californica.", "content": "1. The defensive withdrawal reflex of the siphon of Aplysia is a local response (exhibited by the organ that is stimulated) mediated by the conjoint action of both the central and peripheral nervous systems. 2. Three independent methods were used to determine the contribution of the central and peripheral nervous systems to the siphon-withdrawal reflex: 1) acute reversible deganglionation, 2) chronic deganglionation, and 3) a selective reversible hyperpolarization. With each of these techniques, the central nervous system was found to contribute about 55% of the total reflex. 3. Seven motor neurons were identified and characterized with respect to their electrophysiological properties and the motor actions. Three of the central motor cells belong to the LD clusters of cells (LDS1, LDS2, LDS3) and one is an RD cell (RDS). These four cells all receive excitatory synaptic input from siphon stimulation, excitatory synaptic input from the activity of the respiratory command cells network (interneuron II). large spontaneous IPSPs, and exhibit hyperpolarizing responses (H response) to iontophoretically applied acetylcholine (ACh). These cells all participate in the siphon-withdrawal component of a centrally commanded fixed-action pattern: spontaneous pumping movements of the mantle organs driven by the respiratory command cells. They receive an EPSP burst during the activity of the respiratory command cells and are competent to mediate the siphon motion. Three central siphon motor cells belong to the LB cluster (LBS1, LBS2, LBS3). These cells also receive excitatory input following stimulation of the siphon, a spontaneously occurring IPSP, and have H response to iontophoretically applied ACh. These cells, however, receive an IPSP burst during spontaneous pumping movement and thus do not participate in the active contraction phase of this behavior. LBS1 and LDS1 were examined with respect to their transmitter biochemistry and were found to be noncholinergic. 4. The siphon-withdrawal reflex habituates with comparable kinetics to repeated tactile stimulation when it is under central and peripheral control and when it is under peripheral control only. Thus, not only do both systems act conjointly to produce the defensive withdrawal reflex, but also they have similar response properties and are well matched to mediate the two parts of this siphon behavior.", "contents": "Central and peripheral control of siphon-withdrawal reflex in Aplysia californica. 1. The defensive withdrawal reflex of the siphon of Aplysia is a local response (exhibited by the organ that is stimulated) mediated by the conjoint action of both the central and peripheral nervous systems. 2. Three independent methods were used to determine the contribution of the central and peripheral nervous systems to the siphon-withdrawal reflex: 1) acute reversible deganglionation, 2) chronic deganglionation, and 3) a selective reversible hyperpolarization. With each of these techniques, the central nervous system was found to contribute about 55% of the total reflex. 3. Seven motor neurons were identified and characterized with respect to their electrophysiological properties and the motor actions. Three of the central motor cells belong to the LD clusters of cells (LDS1, LDS2, LDS3) and one is an RD cell (RDS). These four cells all receive excitatory synaptic input from siphon stimulation, excitatory synaptic input from the activity of the respiratory command cells network (interneuron II). large spontaneous IPSPs, and exhibit hyperpolarizing responses (H response) to iontophoretically applied acetylcholine (ACh). These cells all participate in the siphon-withdrawal component of a centrally commanded fixed-action pattern: spontaneous pumping movements of the mantle organs driven by the respiratory command cells. They receive an EPSP burst during the activity of the respiratory command cells and are competent to mediate the siphon motion. Three central siphon motor cells belong to the LB cluster (LBS1, LBS2, LBS3). These cells also receive excitatory input following stimulation of the siphon, a spontaneously occurring IPSP, and have H response to iontophoretically applied ACh. These cells, however, receive an IPSP burst during spontaneous pumping movement and thus do not participate in the active contraction phase of this behavior. LBS1 and LDS1 were examined with respect to their transmitter biochemistry and were found to be noncholinergic. 4. The siphon-withdrawal reflex habituates with comparable kinetics to repeated tactile stimulation when it is under central and peripheral control and when it is under peripheral control only. Thus, not only do both systems act conjointly to produce the defensive withdrawal reflex, but also they have similar response properties and are well matched to mediate the two parts of this siphon behavior."}
{"id": "PMID:217975", "title": "Intracellular study of tonic-type enteric neurons in guinea pig small intestine.", "content": "1. Intracellular recording revealed a population of myenteric neurons with electrical behavior that appeared to be equivalent to the tonic-type mechanosensitive neurons found in earlier studies that utilized extracellular recording of single units. 2. Electrical stimulation of the interganglionic fiber tracts evoked a slowly rising excitatory postsynaptic potential (slow EPSP) that was prolonged for several seconds after termination of the stimulus in these cells. The slow EPSP was associated with increased input resistance and augmented excitability of the somal membrane. The somal membranes had relatively low excitability in the absence of fiber tract stimulation. This was indicated by: 1) failure of depolarizing current pulses to elicit spike discharge in some cells; 2) when spikes were elicited by depolarizing current pulses, one to three spikes occurred, and these were seen only at the onset of the pulse; 3) passive invasion of the soma by current from spikes in the cell's processes did not trigger spikes; 4) the spikes were followed by prolonged hyperpolarizing afterpotentials associated with decreased input resistance. 3. Characteristics of the augmented excitability during the slow EPSP were: 1) endogenous discharge of trains of spikes, 2) spike discharge throughout 200 ms duration depolarizing current pulses, 3) electrotonic spike potentials from the processes triggered somal spikes, 4) postspike afterhyperpolarization was reduced or abolished. 4. The slow EPSP was reduced or abolished in Krebs solution with 16 mM Mg+2 and in HEPES-buffered Krebs with 1 mM Mn2+. It was enhanced in Krebs solution with 3 times normal Ca2+. Spike discharge in elevated Ca2+ eliminated the increase in input resistance associated with the slow EPSP. 5. Calcium availability was an important factor in regulation of membrane conductance and excitability in the perikaryon. The slow EPSP provides a mechanism whereby the soma of a multipolar neuron gates the spread of excitation between its dendrites and axon.", "contents": "Intracellular study of tonic-type enteric neurons in guinea pig small intestine. 1. Intracellular recording revealed a population of myenteric neurons with electrical behavior that appeared to be equivalent to the tonic-type mechanosensitive neurons found in earlier studies that utilized extracellular recording of single units. 2. Electrical stimulation of the interganglionic fiber tracts evoked a slowly rising excitatory postsynaptic potential (slow EPSP) that was prolonged for several seconds after termination of the stimulus in these cells. The slow EPSP was associated with increased input resistance and augmented excitability of the somal membrane. The somal membranes had relatively low excitability in the absence of fiber tract stimulation. This was indicated by: 1) failure of depolarizing current pulses to elicit spike discharge in some cells; 2) when spikes were elicited by depolarizing current pulses, one to three spikes occurred, and these were seen only at the onset of the pulse; 3) passive invasion of the soma by current from spikes in the cell's processes did not trigger spikes; 4) the spikes were followed by prolonged hyperpolarizing afterpotentials associated with decreased input resistance. 3. Characteristics of the augmented excitability during the slow EPSP were: 1) endogenous discharge of trains of spikes, 2) spike discharge throughout 200 ms duration depolarizing current pulses, 3) electrotonic spike potentials from the processes triggered somal spikes, 4) postspike afterhyperpolarization was reduced or abolished. 4. The slow EPSP was reduced or abolished in Krebs solution with 16 mM Mg+2 and in HEPES-buffered Krebs with 1 mM Mn2+. It was enhanced in Krebs solution with 3 times normal Ca2+. Spike discharge in elevated Ca2+ eliminated the increase in input resistance associated with the slow EPSP. 5. Calcium availability was an important factor in regulation of membrane conductance and excitability in the perikaryon. The slow EPSP provides a mechanism whereby the soma of a multipolar neuron gates the spread of excitation between its dendrites and axon."}
{"id": "PMID:217976", "title": "Serotonergic activation of tonic-type enteric neurons in guinea pig small bowel.", "content": "1. Electrical stimulation of interganglionic fiber tracts of Auerbach's plexus released a chemical substance, which produced a slow EPSP associated with an increase in input resistance in the postsynaptic neuron. 2. This effect of fiber tract stimulation was mimicked by microiontophoretic application of serotonin (5-HT) to the neurons. Both the endogenous transmitter substance and exogenous 5-HT produced membrane depolarization, both increased the input resistance of the neuron, both reduced or abolished hyperpolarizing afterpotentials of the action potentials, and both augmented membrane excitability. 3. During tachyphylaxis to excess 5-HT (1 micron) in the perfusion solution, the response to fiber tract stimulation was also reversibly blocked. 4. Methysergide (30 micron) blocked both the response to fiber tract stimulation and to exogenous 5-HT. 5. Cholinergic agonists and antagonists did not alter the slow EPSP and the response to exogenous 5-HT. 6. The evidence suggests that 5-HT is the neurotransmitter substance that produces the slow EPSP in myenteric neurons.", "contents": "Serotonergic activation of tonic-type enteric neurons in guinea pig small bowel. 1. Electrical stimulation of interganglionic fiber tracts of Auerbach's plexus released a chemical substance, which produced a slow EPSP associated with an increase in input resistance in the postsynaptic neuron. 2. This effect of fiber tract stimulation was mimicked by microiontophoretic application of serotonin (5-HT) to the neurons. Both the endogenous transmitter substance and exogenous 5-HT produced membrane depolarization, both increased the input resistance of the neuron, both reduced or abolished hyperpolarizing afterpotentials of the action potentials, and both augmented membrane excitability. 3. During tachyphylaxis to excess 5-HT (1 micron) in the perfusion solution, the response to fiber tract stimulation was also reversibly blocked. 4. Methysergide (30 micron) blocked both the response to fiber tract stimulation and to exogenous 5-HT. 5. Cholinergic agonists and antagonists did not alter the slow EPSP and the response to exogenous 5-HT. 6. The evidence suggests that 5-HT is the neurotransmitter substance that produces the slow EPSP in myenteric neurons."}
{"id": "PMID:217977", "title": "Macrophages in experimental and human brain tumors. Part 1: Studies of the macrophage content of experimental rat brain tumors of varying immunogenicity.", "content": "Although the presence of lymphoreticular cells within tumors has been recognized for over 100 years, it is only within the last decade that the concept has arisen that standard histological examination techniques may lead to an underestimation of the true extent of tumor infiltration by lymphoreticular cells, and particularly by macrophages. The macrophage content of certain systemic tumors has been correlated with their immunogenicity and growth characteristics. Since the central nervous system is to some extent an \"immunologically privileged site\" and contains within it specialized reticuloendothelial cells called microglia, the authors determined the macrophage content of three rodent brain-tumor cell lines, and attempted to correlate this macrophage content with their immunogenicity and growth characteristics. Their findings indicate a direct correlation between the immunogenicity and macrophage content of these three neural tumor cell lines.", "contents": "Macrophages in experimental and human brain tumors. Part 1: Studies of the macrophage content of experimental rat brain tumors of varying immunogenicity. Although the presence of lymphoreticular cells within tumors has been recognized for over 100 years, it is only within the last decade that the concept has arisen that standard histological examination techniques may lead to an underestimation of the true extent of tumor infiltration by lymphoreticular cells, and particularly by macrophages. The macrophage content of certain systemic tumors has been correlated with their immunogenicity and growth characteristics. Since the central nervous system is to some extent an \"immunologically privileged site\" and contains within it specialized reticuloendothelial cells called microglia, the authors determined the macrophage content of three rodent brain-tumor cell lines, and attempted to correlate this macrophage content with their immunogenicity and growth characteristics. Their findings indicate a direct correlation between the immunogenicity and macrophage content of these three neural tumor cell lines."}
{"id": "PMID:217979", "title": "The psychiatric clinical specialist in the general hospital.", "content": "The author describes her experience as a psychiatric clinical nurse specialist functioning independently in a general hospital in a variety of roles. Seven areas of involvement illustrate the wide range of patient, staff, and other needs which this nurse specialist can meet. The author wishes to thank Joanne Damon, R.N., Sandra Zion, R.N., Dorothy Markay, R.N., and Rachel Rotkovitch, R.N., for their advice, encouragement, and support, and Florence Williams, R.N., who provided clinical supervision.", "contents": "The psychiatric clinical specialist in the general hospital. The author describes her experience as a psychiatric clinical nurse specialist functioning independently in a general hospital in a variety of roles. Seven areas of involvement illustrate the wide range of patient, staff, and other needs which this nurse specialist can meet. The author wishes to thank Joanne Damon, R.N., Sandra Zion, R.N., Dorothy Markay, R.N., and Rachel Rotkovitch, R.N., for their advice, encouragement, and support, and Florence Williams, R.N., who provided clinical supervision."}
{"id": "PMID:217983", "title": "Factors affecting the rate of incorporation of a false transmitter into mammalian motor nerve terminals.", "content": "1. The incorporation of acetylmonoethylcholine (AMECh) into transmitter store at the mammalian neuromuscular junction has been studied using electrophysiological techniques. 2. Incubation of rat muscle in the presence of 0.1 mM-monoethylcholine (MECh) and 40 mM-K+ for 60-90 min produced a maximal reduction in the time constant of decay of synaptic currents and potentials, indicating that acetylcholine (ACh) had been replaced by AMECh in the released quanta. 3. Under resting conditions, muscles incubated for up to 24 hr in the presence of MECh showed no incorporation of AMECh into the released transmitter. In contrast, muscles pre-loaded with AMECh and then incubated in choline-containing medium showed a substantial reversion to ACh in the released transmitter within 4 hr. 4. It is suggested that this difference results from the rate of synthesis or packaging of transmitter being considerably slower with MECh than with choline, so that stimulation in the presence of MECh causes an over-all depletion of transmitter stores that does not occur with choline as the precursor. Measurements of m.e.p.c. amplitude following K+-evoked release in the presence of MECh or choline confirmed this interpretation. 5. In order to test whether newly formed AMECh is incorporated into a single homogeneous pool of transmitter from which the released quanta are derived, the rate of incorporation of AMECh into the released transmitter was measured as a function of the number of quanta released when transmitter output was increased by various methods. 6. The number of quanta released before 63% conversion of the released transmitter to AMECh was brought about varied from 1.3 X 10(5) (nerve stimulation at 3 Hz) to about 4 X 10(5) (release by high-K+ solution). With nerve stimulation in Mg2+-blocked muscles the value was 2.5 X 10(5). 7. Incorporation of AMECh into the quanta released by nerve stimulation appeared to take place more rapidly than its incorporation into spontaneously released quanta. 8. These results are discussed in terms of the compartmentation of transmitter stores in the nerve terminals.", "contents": "Factors affecting the rate of incorporation of a false transmitter into mammalian motor nerve terminals. 1. The incorporation of acetylmonoethylcholine (AMECh) into transmitter store at the mammalian neuromuscular junction has been studied using electrophysiological techniques. 2. Incubation of rat muscle in the presence of 0.1 mM-monoethylcholine (MECh) and 40 mM-K+ for 60-90 min produced a maximal reduction in the time constant of decay of synaptic currents and potentials, indicating that acetylcholine (ACh) had been replaced by AMECh in the released quanta. 3. Under resting conditions, muscles incubated for up to 24 hr in the presence of MECh showed no incorporation of AMECh into the released transmitter. In contrast, muscles pre-loaded with AMECh and then incubated in choline-containing medium showed a substantial reversion to ACh in the released transmitter within 4 hr. 4. It is suggested that this difference results from the rate of synthesis or packaging of transmitter being considerably slower with MECh than with choline, so that stimulation in the presence of MECh causes an over-all depletion of transmitter stores that does not occur with choline as the precursor. Measurements of m.e.p.c. amplitude following K+-evoked release in the presence of MECh or choline confirmed this interpretation. 5. In order to test whether newly formed AMECh is incorporated into a single homogeneous pool of transmitter from which the released quanta are derived, the rate of incorporation of AMECh into the released transmitter was measured as a function of the number of quanta released when transmitter output was increased by various methods. 6. The number of quanta released before 63% conversion of the released transmitter to AMECh was brought about varied from 1.3 X 10(5) (nerve stimulation at 3 Hz) to about 4 X 10(5) (release by high-K+ solution). With nerve stimulation in Mg2+-blocked muscles the value was 2.5 X 10(5). 7. Incorporation of AMECh into the quanta released by nerve stimulation appeared to take place more rapidly than its incorporation into spontaneously released quanta. 8. These results are discussed in terms of the compartmentation of transmitter stores in the nerve terminals."}
{"id": "PMID:217984", "title": "Transmitter release from normal and degenerating locust motor nerve terminals.", "content": "1. An analysis has been made of spontaneous and evoked transmitter release from terminals of 'fast' excitatory motor axons on locust muscle fibres using intra- and extracellular recording together with a Ca-electrode technique for activating transmitter release from single nerve terminals on multiterminally innervated muscle fibres. 2. Spontaneous intracellular miniature excitatory junction potentials (m.e.j.p.s), recorded at active spots on these muscle fibres, occurred non-randomly with frequent bursts of m.e.j.p.s. 3. M.e.j.p.s of subnormal amplitude were also seen but contributed only a small fraction of the minature discharge. 4. The amplitude distribution of intracellularly recorded excitatory junction potentials (e.j.p.s) evoked during ionophoretic application of Ca onto single nerve terminals was adequately predicted by Poisson statistics. 5. During the course of nerve terminal degeneration m.e.j.p.s of subnormal amplitude became more frequent and eventually formed the major part of the miniature discharge. Transmitter quanta responsible for 'small' m.e.j.p.s did not contribute to evoked release either at normal or degenerating terminals. Evoked transmitter release from degenerating axon terminals before excitation-secretion coupling failure conformed to Poisson statistics. 6. It is concluded that more than one release mechanism operates on the transmitter pool or pools in locust motor nerve terminals.", "contents": "Transmitter release from normal and degenerating locust motor nerve terminals. 1. An analysis has been made of spontaneous and evoked transmitter release from terminals of 'fast' excitatory motor axons on locust muscle fibres using intra- and extracellular recording together with a Ca-electrode technique for activating transmitter release from single nerve terminals on multiterminally innervated muscle fibres. 2. Spontaneous intracellular miniature excitatory junction potentials (m.e.j.p.s), recorded at active spots on these muscle fibres, occurred non-randomly with frequent bursts of m.e.j.p.s. 3. M.e.j.p.s of subnormal amplitude were also seen but contributed only a small fraction of the minature discharge. 4. The amplitude distribution of intracellularly recorded excitatory junction potentials (e.j.p.s) evoked during ionophoretic application of Ca onto single nerve terminals was adequately predicted by Poisson statistics. 5. During the course of nerve terminal degeneration m.e.j.p.s of subnormal amplitude became more frequent and eventually formed the major part of the miniature discharge. Transmitter quanta responsible for 'small' m.e.j.p.s did not contribute to evoked release either at normal or degenerating terminals. Evoked transmitter release from degenerating axon terminals before excitation-secretion coupling failure conformed to Poisson statistics. 6. It is concluded that more than one release mechanism operates on the transmitter pool or pools in locust motor nerve terminals."}
{"id": "PMID:217985", "title": "Graded synaptic transmission between local interneurones and motor neurones in the metathoracic ganglion of the locust.", "content": "1. In the metathoracic ganglion of the locust some neurones can effect changes in the membrane potential of identified post-synaptic motor neurones without themselves spiking. 2. These 'non-spiking' neurones have processes only within the metathoracic ganglion, and therefore are local intraganglionic interneurones. 3. The absence of spikes in the interneurones reflects their normal physiological state and is not due to the experimental conditions. 4. When the interneurones are depolarized by the injection of current pulses lasting several hundred milliseconds, post-synaptic motor neurones are either depolarized, or hyperpolarized, for the duration of the pulse. 5. The magnitude of the change in post-synaptic voltage is graded according to the amount of presynaptic current. 6. A number of physiological tests indicate that the graded effects upon motor neurones are mediated by chemical synaptic transmission. For example, an evoked hyperpolarization of a motor neurone can be reversed in polarity by simultaneously hyperpolarizing the motor neurone with injected current. 7. At their resting potential some interneurones tonically release sufficient transmitter to have a measurable post-synaptic effect. The injection of depolarizing and hyperpolarizing currents into these interneurones effects opposite changes in post-synaptic potential. 8. Other interneurones must be depolarized from resting potential before a post-synaptic effect is observed, and hyperpolarizing currents have no post-synaptic effect. In these interneurones it is estimated that a depolarization of only 2 mV is sufficient to effect the release of transmitter. 9. The membrane potentials of non-spiking interneurones can fluctuate by as much as 15 mV during active movements of the hind legs and individual p.s.p.s as large as 5 mV can be recorded. Therefore, summed p.s.p.s or even single ones are expected to be the electrophysiological signals effecting transmitter release from these interneurones.", "contents": "Graded synaptic transmission between local interneurones and motor neurones in the metathoracic ganglion of the locust. 1. In the metathoracic ganglion of the locust some neurones can effect changes in the membrane potential of identified post-synaptic motor neurones without themselves spiking. 2. These 'non-spiking' neurones have processes only within the metathoracic ganglion, and therefore are local intraganglionic interneurones. 3. The absence of spikes in the interneurones reflects their normal physiological state and is not due to the experimental conditions. 4. When the interneurones are depolarized by the injection of current pulses lasting several hundred milliseconds, post-synaptic motor neurones are either depolarized, or hyperpolarized, for the duration of the pulse. 5. The magnitude of the change in post-synaptic voltage is graded according to the amount of presynaptic current. 6. A number of physiological tests indicate that the graded effects upon motor neurones are mediated by chemical synaptic transmission. For example, an evoked hyperpolarization of a motor neurone can be reversed in polarity by simultaneously hyperpolarizing the motor neurone with injected current. 7. At their resting potential some interneurones tonically release sufficient transmitter to have a measurable post-synaptic effect. The injection of depolarizing and hyperpolarizing currents into these interneurones effects opposite changes in post-synaptic potential. 8. Other interneurones must be depolarized from resting potential before a post-synaptic effect is observed, and hyperpolarizing currents have no post-synaptic effect. In these interneurones it is estimated that a depolarization of only 2 mV is sufficient to effect the release of transmitter. 9. The membrane potentials of non-spiking interneurones can fluctuate by as much as 15 mV during active movements of the hind legs and individual p.s.p.s as large as 5 mV can be recorded. Therefore, summed p.s.p.s or even single ones are expected to be the electrophysiological signals effecting transmitter release from these interneurones."}
{"id": "PMID:217986", "title": "Variability of transmitter quanta released during incorporation of a false transmitter into cholinergic nerve terminals.", "content": "1. Electrophysiological techniques have been used to investigate the variability of quanta released during various stages of the incorporation of acetylmonoethylcholine (AMECh) into the transmitter store at the neuromuscular junction.2. Stimulation of the rat phrenic nerve-diaphragm preparation at 3 Hz for 15-25 min reduced the time constant of decay tau(m.e.p.c.) of miniature end-plate currents from 1.61 +/- 0.08 (mean +/- S.E. of mean) msec to 1.32 +/- 0.09 msec; this represents 45% replacement of acetylcholine (ACh) by AMECh. Total replacement of ACh was achieved by a further 30-60 min stimulation which reduced tau(m.e.p.c.) to 0.93 +/- 0.06-msec.3. At the intermediate stage of exchange, the coefficient of variation c.v.(tau) of tau(m.e.p.c.) increased from the control value of 0.094 +/- 0.005 to 0.154 +/- 0.012. The latter value was less than the value (0.29) calculated for two distinct populations of quanta (i.e. pure ACh and pure AMECh quanta). Moreover, frequency distribution histograms of tau(m.e.p.c.) did not reveal a bimodal distribution. Total replacement of ACh by AMECh achieved by the second period of stimulation decreased c.v.(tau) towards the control value.4. Pre-incubation of muscles with MECh (to replace any stored choline) or stimulation in the presence of a cholinesterase inhibitor (to prevent ACh destruction and hence re-uptake of choline) did not produce any greater degree of heterogeneity than was seen in the absence of these procedures.5. The increase in c.v.(tau) observed at the intermediate stage of replacement disappeared spontaneously with a half-time of about 1 hr at 20 degrees C.6. These results are discussed in terms of the vesicle hypothesis.", "contents": "Variability of transmitter quanta released during incorporation of a false transmitter into cholinergic nerve terminals. 1. Electrophysiological techniques have been used to investigate the variability of quanta released during various stages of the incorporation of acetylmonoethylcholine (AMECh) into the transmitter store at the neuromuscular junction.2. Stimulation of the rat phrenic nerve-diaphragm preparation at 3 Hz for 15-25 min reduced the time constant of decay tau(m.e.p.c.) of miniature end-plate currents from 1.61 +/- 0.08 (mean +/- S.E. of mean) msec to 1.32 +/- 0.09 msec; this represents 45% replacement of acetylcholine (ACh) by AMECh. Total replacement of ACh was achieved by a further 30-60 min stimulation which reduced tau(m.e.p.c.) to 0.93 +/- 0.06-msec.3. At the intermediate stage of exchange, the coefficient of variation c.v.(tau) of tau(m.e.p.c.) increased from the control value of 0.094 +/- 0.005 to 0.154 +/- 0.012. The latter value was less than the value (0.29) calculated for two distinct populations of quanta (i.e. pure ACh and pure AMECh quanta). Moreover, frequency distribution histograms of tau(m.e.p.c.) did not reveal a bimodal distribution. Total replacement of ACh by AMECh achieved by the second period of stimulation decreased c.v.(tau) towards the control value.4. Pre-incubation of muscles with MECh (to replace any stored choline) or stimulation in the presence of a cholinesterase inhibitor (to prevent ACh destruction and hence re-uptake of choline) did not produce any greater degree of heterogeneity than was seen in the absence of these procedures.5. The increase in c.v.(tau) observed at the intermediate stage of replacement disappeared spontaneously with a half-time of about 1 hr at 20 degrees C.6. These results are discussed in terms of the vesicle hypothesis."}
{"id": "PMID:217988", "title": "The metabolic and endocrine effects of circulating catecholamines in fetal sheep.", "content": "1. Adrenaline and noradrenaline have been infused into the fetal sheep to produce plasma concentrations comparable to those seen during hypoxia. The effects have been compared with those of isoprenaline and methoxamine and the sensitivity to beta- and alpha-adrenergic antagonists has been followed. 2. Adrenaline caused an alpha-mediated increase in blood glucose that is associated with a fall in plasma insulin concentration. It also caused a beta-mediated increase in plasma lactate, free fatty acid and amino acid concentrations. 3. Noradrenaline was much less effective than adrenaline at eliciting metabolic responses. It had not cause a significant change in plasma glucose concentration, although this was associated with a small increase in plasma insulin concentration. It caused a small rise in the concentration of lactate and free fatty acids in fetal plasma but had no effect on plasma amino acids. 4. The beta- and alpha-adrenergic antagonists propranolol and phentolamine alone were without effect on any of the plasma metabolites or hormones assayed. Isoprenaline increased plasma glucose, lactate, free fatty acid, alanine and insulin concentrations, while methoxamine only increased plasma glucose and lactate, and this was associated with a fall in insulin concentration. 5. The concentration of ACTH in fetal plasma was increased by adrenaline and to a lesser extent by noradrenaline and methoxamine; these were blocked by phentolamine. Isoprenaline also caused a small increase in ACTH. There were no corticosteroid changes associated with the increase in ACTH. 6. The results have been discussed in relation to the adrenergic and pancreatic control of metabolism in the fetal sheep.", "contents": "The metabolic and endocrine effects of circulating catecholamines in fetal sheep. 1. Adrenaline and noradrenaline have been infused into the fetal sheep to produce plasma concentrations comparable to those seen during hypoxia. The effects have been compared with those of isoprenaline and methoxamine and the sensitivity to beta- and alpha-adrenergic antagonists has been followed. 2. Adrenaline caused an alpha-mediated increase in blood glucose that is associated with a fall in plasma insulin concentration. It also caused a beta-mediated increase in plasma lactate, free fatty acid and amino acid concentrations. 3. Noradrenaline was much less effective than adrenaline at eliciting metabolic responses. It had not cause a significant change in plasma glucose concentration, although this was associated with a small increase in plasma insulin concentration. It caused a small rise in the concentration of lactate and free fatty acids in fetal plasma but had no effect on plasma amino acids. 4. The beta- and alpha-adrenergic antagonists propranolol and phentolamine alone were without effect on any of the plasma metabolites or hormones assayed. Isoprenaline increased plasma glucose, lactate, free fatty acid, alanine and insulin concentrations, while methoxamine only increased plasma glucose and lactate, and this was associated with a fall in insulin concentration. 5. The concentration of ACTH in fetal plasma was increased by adrenaline and to a lesser extent by noradrenaline and methoxamine; these were blocked by phentolamine. Isoprenaline also caused a small increase in ACTH. There were no corticosteroid changes associated with the increase in ACTH. 6. The results have been discussed in relation to the adrenergic and pancreatic control of metabolism in the fetal sheep."}
{"id": "PMID:217992", "title": "Contacts between receptors and electrophysiologically identified neurones in the retina of the larval tiger salamander.", "content": "1. Following the intracellular recording of bipolar and horizontal cell responses, each unit was injected with horseradish peroxidase and a histochemical staining used to identify it at the level of the light and electron microscopes.2. Centre-depolarizing bipolar cells made contact with rods and cones at basal and ribbon junctions, the latter being fewer. Centre-hyperpolarizing bipolar cells made the same types of contacts with the receptors, but ribbon junctions predominated.3. It appears, therefore, that there is no fixed relationship between the sign of synaptic transmission from receptors to bipolar cells and the junctional features revealed by present methods for electron microscopy of tissue sections. Accordingly, the reason for the existence of more than one type of contact between receptors and bipolar cells remains to be determined.4. Light microscopy of the peroxidase-injected horizontal cells gave further support to the notion that type B responses are recorded from the cell body, and type A responses from the axon terminal, of a single type of horizontal cell. Electron microscopy showed that the processes (dendrites) originating from the cell body make ribbon and distal junctions with rods and cones, just as shown before for the axon terminals.5. As a result of these observations, it is possible to exclude one of two alternative hypotheses previously proposed to account for the properties of the surround responses recorded from the horizontal cell bodies.", "contents": "Contacts between receptors and electrophysiologically identified neurones in the retina of the larval tiger salamander. 1. Following the intracellular recording of bipolar and horizontal cell responses, each unit was injected with horseradish peroxidase and a histochemical staining used to identify it at the level of the light and electron microscopes.2. Centre-depolarizing bipolar cells made contact with rods and cones at basal and ribbon junctions, the latter being fewer. Centre-hyperpolarizing bipolar cells made the same types of contacts with the receptors, but ribbon junctions predominated.3. It appears, therefore, that there is no fixed relationship between the sign of synaptic transmission from receptors to bipolar cells and the junctional features revealed by present methods for electron microscopy of tissue sections. Accordingly, the reason for the existence of more than one type of contact between receptors and bipolar cells remains to be determined.4. Light microscopy of the peroxidase-injected horizontal cells gave further support to the notion that type B responses are recorded from the cell body, and type A responses from the axon terminal, of a single type of horizontal cell. Electron microscopy showed that the processes (dendrites) originating from the cell body make ribbon and distal junctions with rods and cones, just as shown before for the axon terminals.5. As a result of these observations, it is possible to exclude one of two alternative hypotheses previously proposed to account for the properties of the surround responses recorded from the horizontal cell bodies."}
{"id": "PMID:217994", "title": "Physiological roles of adenosine derivatives which are released during neurotransmission in mammalian brain.", "content": "1. Experiments using synaptosome beds suggested that ATP was released from presynaptic sites and degraded to adenosine in the synaptic cleft and that the resulting adenosine was taken up again into nerve endings where it was re-phosphorylated to ATP. 2. Adenosine derivatives in the synaptic cleft inhibited the postsynaptic potentials in olfactory cortex slices in vitro, presumably by the inhibition of Ca2+ influx into nerve endings which resulted in the reduction of transmitter release. 3. The adenosine derivatives also increased the level of cyclic AMP in the slices under the same conditions as above. 4. Although the nature of the \"adenosine receptors\" for both functions was remarkably similar, the increase of cyclic AMP did not mediate the inhibitory action, but the presynaptic increase of cyclic AMP induced by adenosine derivatives might mediate the facilitation observed in the olfactory cortex. 5. Possible physiological roles of extracellular adenosine derivatives in mammalian brain were classified, at different sites of action around the synapses, with different time courses and modes of action, directly or via the increase of intracellular cyclic AMP.", "contents": "Physiological roles of adenosine derivatives which are released during neurotransmission in mammalian brain. 1. Experiments using synaptosome beds suggested that ATP was released from presynaptic sites and degraded to adenosine in the synaptic cleft and that the resulting adenosine was taken up again into nerve endings where it was re-phosphorylated to ATP. 2. Adenosine derivatives in the synaptic cleft inhibited the postsynaptic potentials in olfactory cortex slices in vitro, presumably by the inhibition of Ca2+ influx into nerve endings which resulted in the reduction of transmitter release. 3. The adenosine derivatives also increased the level of cyclic AMP in the slices under the same conditions as above. 4. Although the nature of the \"adenosine receptors\" for both functions was remarkably similar, the increase of cyclic AMP did not mediate the inhibitory action, but the presynaptic increase of cyclic AMP induced by adenosine derivatives might mediate the facilitation observed in the olfactory cortex. 5. Possible physiological roles of extracellular adenosine derivatives in mammalian brain were classified, at different sites of action around the synapses, with different time courses and modes of action, directly or via the increase of intracellular cyclic AMP."}
{"id": "PMID:217995", "title": "5'-adenine mononucleotides in preparations from guinea pig cerebral cortex. Accumulation, translocation and release.", "content": "Isolated nerve terminals (synaptosome beds) were prepared from the neocortex of guinea pig and their ability to accumulate and release adenine nucleotides was studied. Synaptosome beds prelabelled with [14C]adenosine released newly synthesized [14C] adenine derivatives on superfusion. Electrical stimulation and K+ depolarization gave augmented output of both [14C] adenine derivatives and lactate from the preparations. Action of metabolic inhibitors on this output was examined. During incubation and superfusion, the synaptosomes displayed glycolysis and synthesis of ATP. Supply of adenine derivatives to the nerve terminals also occurred by translocation from other parts of the tissue.", "contents": "5'-adenine mononucleotides in preparations from guinea pig cerebral cortex. Accumulation, translocation and release. Isolated nerve terminals (synaptosome beds) were prepared from the neocortex of guinea pig and their ability to accumulate and release adenine nucleotides was studied. Synaptosome beds prelabelled with [14C]adenosine released newly synthesized [14C] adenine derivatives on superfusion. Electrical stimulation and K+ depolarization gave augmented output of both [14C] adenine derivatives and lactate from the preparations. Action of metabolic inhibitors on this output was examined. During incubation and superfusion, the synaptosomes displayed glycolysis and synthesis of ATP. Supply of adenine derivatives to the nerve terminals also occurred by translocation from other parts of the tissue."}
{"id": "PMID:217996", "title": "The release of ATP triggered by transmitter action and its possible physiological significance: retrograde transmission.", "content": "1. When a slice of electric organ of Torpedo is stimulated and superfused with a solution containing a firefly lantern extract, it is possible to measure the release of ATP after each nerve impulse as a light emission. 2. The postsynaptic action of released ACh induces the release of ATP by the postsynaptic cell. Most of the released ATP is of postsynaptic origin. 3. Ion fluxes associated with depolarization, or depolarization itself, trigger the release of ATP from postsynaptic and presynaptic membranes (synaptosomes). 4. ATP is able to block ACh release; a postsynaptic \"retrograde transmission\" able to control presynaptic transmitter release is possible.", "contents": "The release of ATP triggered by transmitter action and its possible physiological significance: retrograde transmission. 1. When a slice of electric organ of Torpedo is stimulated and superfused with a solution containing a firefly lantern extract, it is possible to measure the release of ATP after each nerve impulse as a light emission. 2. The postsynaptic action of released ACh induces the release of ATP by the postsynaptic cell. Most of the released ATP is of postsynaptic origin. 3. Ion fluxes associated with depolarization, or depolarization itself, trigger the release of ATP from postsynaptic and presynaptic membranes (synaptosomes). 4. ATP is able to block ACh release; a postsynaptic \"retrograde transmission\" able to control presynaptic transmitter release is possible."}
{"id": "PMID:217997", "title": "Mechanisms of depression of neuromuscular transmission by ATP and adenosine.", "content": "1. The effects of ATP in the presence of theophylline and imidazole were investigated on the twitch tension of a partially magnesium blocked rat phrenic nerve-diaphragm preparation. Both theophylline and imidazole facilitate the neuromuscular transmission and prevent the effects of ATP. 2. The effects of adenosine in solutions with low calcium concentrations in the frog-sartorius and in solutions with very low calcium concentrations in the rat-diaphragm were studied on the miniature end-plate potentials. Adenosine caused a similar reduction of the frequency of the miniature end-plate potentials in both low and very low calcium concentrations. 3. The results are discussed in relation to the cyclic AMP and calcium hypothesis.", "contents": "Mechanisms of depression of neuromuscular transmission by ATP and adenosine. 1. The effects of ATP in the presence of theophylline and imidazole were investigated on the twitch tension of a partially magnesium blocked rat phrenic nerve-diaphragm preparation. Both theophylline and imidazole facilitate the neuromuscular transmission and prevent the effects of ATP. 2. The effects of adenosine in solutions with low calcium concentrations in the frog-sartorius and in solutions with very low calcium concentrations in the rat-diaphragm were studied on the miniature end-plate potentials. Adenosine caused a similar reduction of the frequency of the miniature end-plate potentials in both low and very low calcium concentrations. 3. The results are discussed in relation to the cyclic AMP and calcium hypothesis."}
{"id": "PMID:217998", "title": "Adenine nucleotides in cholinergic transmission: presynaptic aspects.", "content": "1. Isolated nerve terminals (T-sacs and synaptosomes) prepared from the purely cholinergic Torpedo electric organ have been studied for their ability to incorporate and metabolise [2-3H] adenosine and to degrade 5'-AMP to adenosine. 2. A temperature-dependent, saturable uptake system for adenosine was found with kinetic properties similar to nucleoside transport systems in other cells. The uptake system in Torpedo nerve terminals was inhibited by 2'-deoxyadenosine, a known inhibitor of adenosine transport. 3. Intraterminal adenosine is rapidly metabolised to a number of products including AMP, ADP and ATP. 4. Isolated nerve terminals contain considerable 5'-nucleotidase activity, most of which resides on the outer face of the external membrane. The Km of the enzyme is congruent to 5 micron and it is inhibited by a phosphonate analogue of ADP, alpha-beta-methylene-ADP. It is suggested that this 5'-nucleotidase plays an important role in the production of adenosine from a nucleotide pool in the synaptic cleft.", "contents": "Adenine nucleotides in cholinergic transmission: presynaptic aspects. 1. Isolated nerve terminals (T-sacs and synaptosomes) prepared from the purely cholinergic Torpedo electric organ have been studied for their ability to incorporate and metabolise [2-3H] adenosine and to degrade 5'-AMP to adenosine. 2. A temperature-dependent, saturable uptake system for adenosine was found with kinetic properties similar to nucleoside transport systems in other cells. The uptake system in Torpedo nerve terminals was inhibited by 2'-deoxyadenosine, a known inhibitor of adenosine transport. 3. Intraterminal adenosine is rapidly metabolised to a number of products including AMP, ADP and ATP. 4. Isolated nerve terminals contain considerable 5'-nucleotidase activity, most of which resides on the outer face of the external membrane. The Km of the enzyme is congruent to 5 micron and it is inhibited by a phosphonate analogue of ADP, alpha-beta-methylene-ADP. It is suggested that this 5'-nucleotidase plays an important role in the production of adenosine from a nucleotide pool in the synaptic cleft."}
{"id": "PMID:218001", "title": "[The role of beta and alpha adrenergic receptors in the lipolytic effect of catecholamines on dog adipocytes (author's transl)].", "content": "Pharmacological properties of adrenergic receptors have been investigated in fat cells isolated from omental adipose tissue of the Dog. From the results, the following points can be stated. 1. Lipolysis is markedly enhanced by isoproterenol. This effect is competitively inhibited by  propranolol (a beta-adrenoceptor blocking agent). (Fig 1). 2. The beta 2-sympathomimetic salbutamol is found to have only a slight effect on lipolysis rate (Fig. 2). 3. The epinephrine-induced lipolysis is potentiated by phentolamine (an alpha-adrenoceptor blocking agent) only on large sized adipose cells (mean fat cell size 96.7 +/- 5.3 micrometer; Fig. 5). 4. The isoproterenol-induced lipolysis is partially inhibited by phenylephrine (an alpha-adrenomimetic drug) (Table I). These findings show that beta 1 nature of the receptors involved in the adrenergic control of lipolysis in Dog adipose tissue. Moreover an antilipolytic effect of epinephrine, via alpha-adrenergic receptors, is observed, especially in large adipose cells.", "contents": "[The role of beta and alpha adrenergic receptors in the lipolytic effect of catecholamines on dog adipocytes (author's transl)]. Pharmacological properties of adrenergic receptors have been investigated in fat cells isolated from omental adipose tissue of the Dog. From the results, the following points can be stated. 1. Lipolysis is markedly enhanced by isoproterenol. This effect is competitively inhibited by  propranolol (a beta-adrenoceptor blocking agent). (Fig 1). 2. The beta 2-sympathomimetic salbutamol is found to have only a slight effect on lipolysis rate (Fig. 2). 3. The epinephrine-induced lipolysis is potentiated by phentolamine (an alpha-adrenoceptor blocking agent) only on large sized adipose cells (mean fat cell size 96.7 +/- 5.3 micrometer; Fig. 5). 4. The isoproterenol-induced lipolysis is partially inhibited by phenylephrine (an alpha-adrenomimetic drug) (Table I). These findings show that beta 1 nature of the receptors involved in the adrenergic control of lipolysis in Dog adipose tissue. Moreover an antilipolytic effect of epinephrine, via alpha-adrenergic receptors, is observed, especially in large adipose cells."}
{"id": "PMID:218003", "title": "Surface smoothness and marginal fit with phosphate-bonded investments.", "content": "Two phosphate-bonded investments and one calcium sulfate investment were evaluated for the surface smoothness and marginal fit they impart to gold castings. A modified technique was also evaluated for each phosphate-bonded investment, where the silica sol was not diluted and the spatulation time was reduced. The results of this study lead to the following conclusions: 1. The marginal fits obtained with all four phosphate-bonded methods were comparable to each other and superior to that obtained with the calcium sulfate investment. 2. The presence of nodules on the surface of the castings was more prevalent with the phosphate-bonded investments. However, this effect was not statistically significant. 3. Clinical assessment of the roughness of the castings revealed that all the methods tested produced clinically acceptable castings. 4. Visual observation by five dentists revealed that both the recommended and modified techniques for one of the phosphate-bonded investments (Ceramigold) produced a smoother surface than any other investment tested. Rating of scanning electron microscope photographs (X600) revealed no difference in the surface roughness between any of the castings. Consequently, no definitive relation between investment type or technique and surface roughness was established. 5. No correlation was demonstrated between surface roughness, as evaluated by either clinical observation or scanning electron microscope photography, and marginal fit of the castings.", "contents": "Surface smoothness and marginal fit with phosphate-bonded investments. Two phosphate-bonded investments and one calcium sulfate investment were evaluated for the surface smoothness and marginal fit they impart to gold castings. A modified technique was also evaluated for each phosphate-bonded investment, where the silica sol was not diluted and the spatulation time was reduced. The results of this study lead to the following conclusions: 1. The marginal fits obtained with all four phosphate-bonded methods were comparable to each other and superior to that obtained with the calcium sulfate investment. 2. The presence of nodules on the surface of the castings was more prevalent with the phosphate-bonded investments. However, this effect was not statistically significant. 3. Clinical assessment of the roughness of the castings revealed that all the methods tested produced clinically acceptable castings. 4. Visual observation by five dentists revealed that both the recommended and modified techniques for one of the phosphate-bonded investments (Ceramigold) produced a smoother surface than any other investment tested. Rating of scanning electron microscope photographs (X600) revealed no difference in the surface roughness between any of the castings. Consequently, no definitive relation between investment type or technique and surface roughness was established. 5. No correlation was demonstrated between surface roughness, as evaluated by either clinical observation or scanning electron microscope photography, and marginal fit of the castings."}
{"id": "PMID:218005", "title": "Some infectious diseases of wild vervet monkeys (Cercopithecus aethiops pygerythrus) in South Africa.", "content": "Our surveys indicate that nearly all batches of vervet monkeys arriving at the National Institute for Virology from various areas of South Africa, are infected with foamy viruses and there is evidence that intra-urterine infection also occurs. Monkeys from certain areas of South Africa are apparently infected with the protozoal parasite Entopolypoides macaci in a sub-clinical state which becomes active when the monkeys are splenectomised. Serological studies indicate that infections with schistosomes, tick-bite fever (Rickettsia conori), chlamydsiae and occasionally by leptospirae, occur in monkeys in the Kruger National Park. Complement fixation tests for antibodies to R. mooseri and R. prowazeki were also sometimes positive; a finding of doubtful importance. There was a high percentage with positive antibody tests to chikungunya virus in a certain age group suggesting that there had been an outbreak of this disease in the Kruger Park in the late summer and autumn of 1976. This coincided with a human outbreak. Large numbers of vervet and baboon sera were tested for antibodies against SA 12 virus, a polyoma virus. A high percentage of baboons but only a small number of monkeys was found to be positive and it is concluded that SA 12 is probably a baboon virus which is occasionally transmitted to monkeys by contact. It is pointed out that these studies only indicate diseases from which monkeys recover and they do not indicate prevalence of severe disease causing grave illness or death.", "contents": "Some infectious diseases of wild vervet monkeys (Cercopithecus aethiops pygerythrus) in South Africa. Our surveys indicate that nearly all batches of vervet monkeys arriving at the National Institute for Virology from various areas of South Africa, are infected with foamy viruses and there is evidence that intra-urterine infection also occurs. Monkeys from certain areas of South Africa are apparently infected with the protozoal parasite Entopolypoides macaci in a sub-clinical state which becomes active when the monkeys are splenectomised. Serological studies indicate that infections with schistosomes, tick-bite fever (Rickettsia conori), chlamydsiae and occasionally by leptospirae, occur in monkeys in the Kruger National Park. Complement fixation tests for antibodies to R. mooseri and R. prowazeki were also sometimes positive; a finding of doubtful importance. There was a high percentage with positive antibody tests to chikungunya virus in a certain age group suggesting that there had been an outbreak of this disease in the Kruger Park in the late summer and autumn of 1976. This coincided with a human outbreak. Large numbers of vervet and baboon sera were tested for antibodies against SA 12 virus, a polyoma virus. A high percentage of baboons but only a small number of monkeys was found to be positive and it is concluded that SA 12 is probably a baboon virus which is occasionally transmitted to monkeys by contact. It is pointed out that these studies only indicate diseases from which monkeys recover and they do not indicate prevalence of severe disease causing grave illness or death."}
{"id": "PMID:218006", "title": "Nucleosides. 110. Synthesis and antiherpes virus activity of some 2'-fluoro-2'-deoxyarabinofuranosylpyrimidine nucleosides.", "content": "A series of 5-substituted 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)cytosines 7a-d and their corresponding uracils 9a-d,f were prepared by condensation of 3-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-D-arabinosyl bromide (5) with appropriately trimethylsilylated pyrimidines followed by saponification of the protected nucleosides 6 or 8. 1-(2-Deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine (7e) was obtained by iodination of 7a. Iodination of 8a followed by removal of the protecting acyl-protecting groups afforded the 5-iodo nucleoside 9e. Several of these 2'-fluoro-substituted nucleosides completely obviated replication of herpes simplex virus type 1 (HSV-1) in monolayers of Vero cells at concentrations of 10-100 microgram/mL. The 5-iodocytosine analogue 7e was the most effective, showing 99.5% suppression of viral replication even at concentrations of 0.1 microgram/mL. The cytotoxicity of 7e to L5178Y or P815 cells in culture was minimal. A comparison of the efficacy of 7e against HSV-1 with other known nucleoside antiviral agents indicates that further in vitro and in vivo evaluation of 7e is warranted.", "contents": "Nucleosides. 110. Synthesis and antiherpes virus activity of some 2'-fluoro-2'-deoxyarabinofuranosylpyrimidine nucleosides. A series of 5-substituted 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)cytosines 7a-d and their corresponding uracils 9a-d,f were prepared by condensation of 3-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-D-arabinosyl bromide (5) with appropriately trimethylsilylated pyrimidines followed by saponification of the protected nucleosides 6 or 8. 1-(2-Deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine (7e) was obtained by iodination of 7a. Iodination of 8a followed by removal of the protecting acyl-protecting groups afforded the 5-iodo nucleoside 9e. Several of these 2'-fluoro-substituted nucleosides completely obviated replication of herpes simplex virus type 1 (HSV-1) in monolayers of Vero cells at concentrations of 10-100 microgram/mL. The 5-iodocytosine analogue 7e was the most effective, showing 99.5% suppression of viral replication even at concentrations of 0.1 microgram/mL. The cytotoxicity of 7e to L5178Y or P815 cells in culture was minimal. A comparison of the efficacy of 7e against HSV-1 with other known nucleoside antiviral agents indicates that further in vitro and in vivo evaluation of 7e is warranted."}
{"id": "PMID:218007", "title": "Hypobetalipoproteinemic agents. 2. Compounds related to 4-(1-adamantyloxy)aniline.", "content": "While the previously used displacement reaction of sodim 1-adamantyl oxide on 4-fluoronitrobenzene was applicable to the preparation of 4-(1-adamantyloxy)aniline and several related compounds, certain derivatives were not easily accessible by this route. Thus the recently reported ortho alkylation of anilines and the dicyclohexylcarbodiimide-promoted coupling of 1-adamantanol with phenols were useful in the preparation of aromatic-substituted derivatives. Furthermore, addition of phenylmagnesium bromide to 1-cyanoadamantane provided entry to the 4-(1-adamantylmethyl)aniline series. 4-(1-Adamantyloxy)aniline (3) is herein reported to be a more potent hypobetalipoproteinemic agent than the previously reported bicyclooctyloxy analogue. Replacement of the oxygen atom of 3 with sulfur (74) or methylene (62), but not nitrogen (71), results in active compounds. In the oxygen series derived from 3, the widest scope of substitution on nitrogen resulting in activity is found. The N-ethoxycarbonyl (5), acetyl (6), methyl (12), ethyl (13), N-methyl-N-(2-hydroxyethyl) (19), N-methyl-N-formyl (22), N,N-dimethyl (26), pyrrolidine (14), and piperidine (15) derivatives are active. Aromatic ring substitution also provided the active 3-chloro (44b), 2-fluoro (41b, 42, and 43), and 2-methylthiomethyl (48) compounds. Thus these active compounds are identified for further development as hypobetalipoproteinemic agents.", "contents": "Hypobetalipoproteinemic agents. 2. Compounds related to 4-(1-adamantyloxy)aniline. While the previously used displacement reaction of sodim 1-adamantyl oxide on 4-fluoronitrobenzene was applicable to the preparation of 4-(1-adamantyloxy)aniline and several related compounds, certain derivatives were not easily accessible by this route. Thus the recently reported ortho alkylation of anilines and the dicyclohexylcarbodiimide-promoted coupling of 1-adamantanol with phenols were useful in the preparation of aromatic-substituted derivatives. Furthermore, addition of phenylmagnesium bromide to 1-cyanoadamantane provided entry to the 4-(1-adamantylmethyl)aniline series. 4-(1-Adamantyloxy)aniline (3) is herein reported to be a more potent hypobetalipoproteinemic agent than the previously reported bicyclooctyloxy analogue. Replacement of the oxygen atom of 3 with sulfur (74) or methylene (62), but not nitrogen (71), results in active compounds. In the oxygen series derived from 3, the widest scope of substitution on nitrogen resulting in activity is found. The N-ethoxycarbonyl (5), acetyl (6), methyl (12), ethyl (13), N-methyl-N-(2-hydroxyethyl) (19), N-methyl-N-formyl (22), N,N-dimethyl (26), pyrrolidine (14), and piperidine (15) derivatives are active. Aromatic ring substitution also provided the active 3-chloro (44b), 2-fluoro (41b, 42, and 43), and 2-methylthiomethyl (48) compounds. Thus these active compounds are identified for further development as hypobetalipoproteinemic agents."}
{"id": "PMID:218008", "title": "3-Substituted adenines. In vitro enzyme inhibition and antiviral activity.", "content": "The direct alkylation of adenine at the 3 position has been extended to produce series of 3-alkyl-, 3-allyl-, and 3-(substituted benzyl)adenines. When these compounds were tested for enzyme inhibition and antiviral activity in vitro, 3-n-pentyladenine was found to be the most active compound in inhibiting the enzyme dopamine-beta-hydroxylase, and 3-(2-bromobenzyl)adenine showed the most striking inhibition of multiplication of Vaccinia virus and of Herpes simplex virus in tissue culture.", "contents": "3-Substituted adenines. In vitro enzyme inhibition and antiviral activity. The direct alkylation of adenine at the 3 position has been extended to produce series of 3-alkyl-, 3-allyl-, and 3-(substituted benzyl)adenines. When these compounds were tested for enzyme inhibition and antiviral activity in vitro, 3-n-pentyladenine was found to be the most active compound in inhibiting the enzyme dopamine-beta-hydroxylase, and 3-(2-bromobenzyl)adenine showed the most striking inhibition of multiplication of Vaccinia virus and of Herpes simplex virus in tissue culture."}
{"id": "PMID:218009", "title": "Synthesis and pharmacologic characterization of an alkylating analogue (chlornaltrexamine) of naltrexone with ultralong-lasting narcotic antagonist properties.", "content": "Chlornaltrexamine (CNA) produces ultralong-lasting (3--6 days) narcotic antagonism in mice and persistent stereospecific binding to rat-brain homogenate. Protection studies in mice suggest that CNA mediates its narcotic antagonist effects by interacting with the same receptors that are occupied by naloxone. A single icv dose of CNA also has been found to inhibit the development of physical dependence in mice for at least 3 days. These studies suggest that CNA exerts its sustained effects by selective covalent association with opioid receptors.", "contents": "Synthesis and pharmacologic characterization of an alkylating analogue (chlornaltrexamine) of naltrexone with ultralong-lasting narcotic antagonist properties. Chlornaltrexamine (CNA) produces ultralong-lasting (3--6 days) narcotic antagonism in mice and persistent stereospecific binding to rat-brain homogenate. Protection studies in mice suggest that CNA mediates its narcotic antagonist effects by interacting with the same receptors that are occupied by naloxone. A single icv dose of CNA also has been found to inhibit the development of physical dependence in mice for at least 3 days. These studies suggest that CNA exerts its sustained effects by selective covalent association with opioid receptors."}
{"id": "PMID:218010", "title": "Easily hydrolyzable, water-soluble derivatives of (+/-)-alpha-5-[1-(indol-3-yl)ethyl]-2-methylamino-delta2-thiazoline-4-one, a novel antiviral compound.", "content": "The preparation of a series of indole N-acyl and N-carbamic esters of (+/-)-alpha-5-[1-(indol-3-yl)ethyl]-2-methylamino-delta2-thiazolin-4-one (1) is reported. These derivatives were synthesized as potential water-soluble precursors of the antiviral thiazolinone 1, for evaluation by intranasal administration against influenza and other respiratory infections caused by viruses. Salts of the basic carbamic esters (16--19) possess the required water solubility, undergo rapid hydrolysis and decarboxylation at pH values greater than 6, and have high activity against influenza A2 and Coxsackie B1 viruses in vitro. In influenza A2 infected ferrets a representative ester (16) reduced the severity and duration of disease symptoms and reduced nasal wash virus titres but caused local irritancy.", "contents": "Easily hydrolyzable, water-soluble derivatives of (+/-)-alpha-5-[1-(indol-3-yl)ethyl]-2-methylamino-delta2-thiazoline-4-one, a novel antiviral compound. The preparation of a series of indole N-acyl and N-carbamic esters of (+/-)-alpha-5-[1-(indol-3-yl)ethyl]-2-methylamino-delta2-thiazolin-4-one (1) is reported. These derivatives were synthesized as potential water-soluble precursors of the antiviral thiazolinone 1, for evaluation by intranasal administration against influenza and other respiratory infections caused by viruses. Salts of the basic carbamic esters (16--19) possess the required water solubility, undergo rapid hydrolysis and decarboxylation at pH values greater than 6, and have high activity against influenza A2 and Coxsackie B1 viruses in vitro. In influenza A2 infected ferrets a representative ester (16) reduced the severity and duration of disease symptoms and reduced nasal wash virus titres but caused local irritancy."}
{"id": "PMID:218011", "title": "A model for thyroid hormone--receptor interactions.", "content": "Theoretical electronic structure calculations on the thyroid hormones and analogues, as well as model hormone--receptor interactions, have been carried out. These studies (a) support the concept that the 4'-OH group is a H-bond donor to the in vivo nuclear receptor and suggest that at the receptor this OH group is trans to the 3' (distal) substituent; (b) indicate that there is an important intramolecular interaction between 3' and 4' substituents, and those 3' substituents that most favor both 4' OH orientation trans to the 3' group and a more acidic OH group substantially increase binding and biological activity; and (c) support the concept that there is a direct correlation between the conformational free energy of the aromatic rings and biological activity.", "contents": "A model for thyroid hormone--receptor interactions. Theoretical electronic structure calculations on the thyroid hormones and analogues, as well as model hormone--receptor interactions, have been carried out. These studies (a) support the concept that the 4'-OH group is a H-bond donor to the in vivo nuclear receptor and suggest that at the receptor this OH group is trans to the 3' (distal) substituent; (b) indicate that there is an important intramolecular interaction between 3' and 4' substituents, and those 3' substituents that most favor both 4' OH orientation trans to the 3' group and a more acidic OH group substantially increase binding and biological activity; and (c) support the concept that there is a direct correlation between the conformational free energy of the aromatic rings and biological activity."}
{"id": "PMID:218012", "title": "Deoxymorphines: role of the phenolic hydroxyl in antinociception and opiate receptor interactions.", "content": "Several 3-deoxy opioids and 3,6-dideoxydihydromorphine was synthesized to ascertain the effect of the phenolic hydroxyl group on antinociceptive potency and receptor binding affinity. Catalytic reduction of the 3-tetrazolyl ether derivatives of dihydromorphine provided the entry into the 3-deoxydihydro series. The prototype, 3-deoxymorphine, was prepared by lithium aluminum hydride reduction of 3-deoxy-N-carbethoxymorphinone, obtained via its 7-(phenylseleno) derivative. 3-Deoxydihydromorphinone and 3,6-dideoxydihydromorphine were found to be about as potent as, or more potent than, morphine in standard antiociceptive assays. Each of them, however, was less potent than the comparable 3-hydroxy analogue, and their binding affinity to the opiate receptor was substantially decreased. The epoxy ring in 3.6-dideoxydihydromorphine was found to increase the antinociceptive potency of the compound.", "contents": "Deoxymorphines: role of the phenolic hydroxyl in antinociception and opiate receptor interactions. Several 3-deoxy opioids and 3,6-dideoxydihydromorphine was synthesized to ascertain the effect of the phenolic hydroxyl group on antinociceptive potency and receptor binding affinity. Catalytic reduction of the 3-tetrazolyl ether derivatives of dihydromorphine provided the entry into the 3-deoxydihydro series. The prototype, 3-deoxymorphine, was prepared by lithium aluminum hydride reduction of 3-deoxy-N-carbethoxymorphinone, obtained via its 7-(phenylseleno) derivative. 3-Deoxydihydromorphinone and 3,6-dideoxydihydromorphine were found to be about as potent as, or more potent than, morphine in standard antiociceptive assays. Each of them, however, was less potent than the comparable 3-hydroxy analogue, and their binding affinity to the opiate receptor was substantially decreased. The epoxy ring in 3.6-dideoxydihydromorphine was found to increase the antinociceptive potency of the compound."}
{"id": "PMID:218013", "title": "Prodrugs of 9-(beta-D-arabinofuranosyl)adenine 2. Synthesis and evaluation of a number of 2',3'- and 3',5'-di-O-acyl derivatives.", "content": "A number of 2',3'- and 3',5'-di-O-acyl derivatives of 9-beta-D-arabinofuranosyladenine (1) were prepared and evaluated as antivirals. These compounds, designed as prodrugs of 1, offer a range of solubilities and lipophilicities, as well as a resistance to adenosine deaminase, that render some as being attractive as possibly useful antiviral agents. Of particular note is 9-(2,3-di-O-acetyl-beta-D-arabinofuranosyl)adenine that was found to be effective as a topical agent in a guinea pig model of genital herpes.", "contents": "Prodrugs of 9-(beta-D-arabinofuranosyl)adenine 2. Synthesis and evaluation of a number of 2',3'- and 3',5'-di-O-acyl derivatives. A number of 2',3'- and 3',5'-di-O-acyl derivatives of 9-beta-D-arabinofuranosyladenine (1) were prepared and evaluated as antivirals. These compounds, designed as prodrugs of 1, offer a range of solubilities and lipophilicities, as well as a resistance to adenosine deaminase, that render some as being attractive as possibly useful antiviral agents. Of particular note is 9-(2,3-di-O-acetyl-beta-D-arabinofuranosyl)adenine that was found to be effective as a topical agent in a guinea pig model of genital herpes."}
{"id": "PMID:218015", "title": "Paradoxical effects of N-cyanoalkyl substituents upon the activities of several classes of opioids.", "content": "The pharmacological effect of the N-(beta-cyanoethyl) moiety is dependent on the opioid on which it is substituted. It caused a large increase in antinociceptive potency, in (--)-3-hydroxymorphinan and (--)-normetazocine, as compared with the N-methyl opioid. These cyanoethyl compounds do not substitute for morphine in morphine-dependent monkeys. This moiety also appears to greatly increase the ability of the opiate receptor to differentiate enantiomers. An ca. 100,000-fold difference in binding was noted between the epimeric N-(beta-cyanoethyl)-3-hydroxymorphinans and the normetazocines. The levo enantiomers have little acute toxicity and showed excellent therapeutic ratios. In contrast, the N-(beta-cyanoethyl) moiety on normorphine, norcodeine, and noroxymorphone did not appear to improve their pharmacological properties. Homologous N-cyanoalkyl opioids were less potent antinociceptives.", "contents": "Paradoxical effects of N-cyanoalkyl substituents upon the activities of several classes of opioids. The pharmacological effect of the N-(beta-cyanoethyl) moiety is dependent on the opioid on which it is substituted. It caused a large increase in antinociceptive potency, in (--)-3-hydroxymorphinan and (--)-normetazocine, as compared with the N-methyl opioid. These cyanoethyl compounds do not substitute for morphine in morphine-dependent monkeys. This moiety also appears to greatly increase the ability of the opiate receptor to differentiate enantiomers. An ca. 100,000-fold difference in binding was noted between the epimeric N-(beta-cyanoethyl)-3-hydroxymorphinans and the normetazocines. The levo enantiomers have little acute toxicity and showed excellent therapeutic ratios. In contrast, the N-(beta-cyanoethyl) moiety on normorphine, norcodeine, and noroxymorphone did not appear to improve their pharmacological properties. Homologous N-cyanoalkyl opioids were less potent antinociceptives."}
{"id": "PMID:218016", "title": "Angiokeratoma corporis diffusum (Anderson-Fabry disease) in a single large family in Nova Scotia.", "content": "Eighteen males, 17 of whom were members of a single family, affected with angiokeratoma corporis diffusum were examined in detail to determine the extent of clinical variation of the expression of what was almost certainly the same X-linked mutation in each. The commonest symptom was episodic bouts of severe, painful dysaesthesia in hands and feet. This was a major complaint of 12, a minor complaint of 5, and absent in 1. In over half the subjects, the skin rash that is considered a characteristic sign of the disease was absent or inconspicuous. All exhibited mild clubbing of fingers and toes, and 15 showed variable limitation of active and passive extension of the 5th fingers bilaterally. Only 2 (age 36 and 47) had evidence of significant renal disease. Electrocardiograms showed abnormally short PR intervals in 4, and right ventricular conduction disturbances in 5. Echocardiograms on 9 showed no evidence of myocardial dysfunction. The marked variation of the expression of some features of the disease indicates that the clinical expression of the mutation is likely to be subject to considerable genetic or environmental modification in each individual.", "contents": "Angiokeratoma corporis diffusum (Anderson-Fabry disease) in a single large family in Nova Scotia. Eighteen males, 17 of whom were members of a single family, affected with angiokeratoma corporis diffusum were examined in detail to determine the extent of clinical variation of the expression of what was almost certainly the same X-linked mutation in each. The commonest symptom was episodic bouts of severe, painful dysaesthesia in hands and feet. This was a major complaint of 12, a minor complaint of 5, and absent in 1. In over half the subjects, the skin rash that is considered a characteristic sign of the disease was absent or inconspicuous. All exhibited mild clubbing of fingers and toes, and 15 showed variable limitation of active and passive extension of the 5th fingers bilaterally. Only 2 (age 36 and 47) had evidence of significant renal disease. Electrocardiograms showed abnormally short PR intervals in 4, and right ventricular conduction disturbances in 5. Echocardiograms on 9 showed no evidence of myocardial dysfunction. The marked variation of the expression of some features of the disease indicates that the clinical expression of the mutation is likely to be subject to considerable genetic or environmental modification in each individual."}
{"id": "PMID:218027", "title": "The treatment of ACTH Paraneoplastic syndrome with aminoglutethimide.", "content": "A 60-year-old white female with oat-cell carcinoma of the lung presents with a recurrent pulmonary nodule and Cushing syndrome. The tumor is uncontrollable with MeCCNU and cyclophosphamide (Cytoxan), consequently the symptoms of Cushing disease become severe. Cushing syndrome is documented by laboratory examinations. Aminoglutethimide, an anticonvulsant, is used to reverse the symptomatology and also the laboratory values. When aminoglutethimide is discontinued, the laboratory findings return to pretreatment levels.", "contents": "The treatment of ACTH Paraneoplastic syndrome with aminoglutethimide. A 60-year-old white female with oat-cell carcinoma of the lung presents with a recurrent pulmonary nodule and Cushing syndrome. The tumor is uncontrollable with MeCCNU and cyclophosphamide (Cytoxan), consequently the symptoms of Cushing disease become severe. Cushing syndrome is documented by laboratory examinations. Aminoglutethimide, an anticonvulsant, is used to reverse the symptomatology and also the laboratory values. When aminoglutethimide is discontinued, the laboratory findings return to pretreatment levels."}
{"id": "PMID:218031", "title": "Lipid peroxidation activity mediated by NADPH-cytochrome C reductase purified from rabbit liver microsomes.", "content": "Purified NADPH-cytochrome c reductase of rabbit liver microsomes was examined to determine whether or not the reported low lipid peroxidation activity of rabbit liver microsomes is due to the enzyme, NADPH-cytochrome c reductase. NADPH-cytochrome c reductase was purified from phenobarbital-treated rabbit liver microsomes to a specific activity of 14.9 to 21.4 unit per mg of protein with a yield of 15.2 to 16.4%. The purified sample (21.4 unit/mg of protein) was almost homogenous as determined by sodium dodecylsulfate gel electrophoresis. This sample was used for determining lipid peroxidation activity. EDTA and ferrous ion but not ADP were essential requirements for the activity. FMN enhanced the activity when low concentrations of the NADPH-cytochrome c reductase were used for the assay. NADP and 2'-AMP, which are inhibitors of NADPH-cytochrome c reductase, inhibited the lipid peroxidation activity. a-Tocopherol and p-chloromercuribenzoate (PCMB) also inhibited the activity. From these results, we confirmed the rabbit liver microsomal enzyme NADPH-cytochrome c reductase plays a role in lipid peroxidation activity. The reported low lipid peroxidation activity in rabbit liver microsomes does not appear to be caused by the NADPH-cytochrome c reductase.", "contents": "Lipid peroxidation activity mediated by NADPH-cytochrome C reductase purified from rabbit liver microsomes. Purified NADPH-cytochrome c reductase of rabbit liver microsomes was examined to determine whether or not the reported low lipid peroxidation activity of rabbit liver microsomes is due to the enzyme, NADPH-cytochrome c reductase. NADPH-cytochrome c reductase was purified from phenobarbital-treated rabbit liver microsomes to a specific activity of 14.9 to 21.4 unit per mg of protein with a yield of 15.2 to 16.4%. The purified sample (21.4 unit/mg of protein) was almost homogenous as determined by sodium dodecylsulfate gel electrophoresis. This sample was used for determining lipid peroxidation activity. EDTA and ferrous ion but not ADP were essential requirements for the activity. FMN enhanced the activity when low concentrations of the NADPH-cytochrome c reductase were used for the assay. NADP and 2'-AMP, which are inhibitors of NADPH-cytochrome c reductase, inhibited the lipid peroxidation activity. a-Tocopherol and p-chloromercuribenzoate (PCMB) also inhibited the activity. From these results, we confirmed the rabbit liver microsomal enzyme NADPH-cytochrome c reductase plays a role in lipid peroxidation activity. The reported low lipid peroxidation activity in rabbit liver microsomes does not appear to be caused by the NADPH-cytochrome c reductase."}
{"id": "PMID:218036", "title": "[Kidney function and Na+-K+-ATPase and succinate dehydrogenase activity in the cells of the renal tubules of rats with constriction of the thoracic portion of the vena cava inferior].", "content": "Circulatory insufficiency in rats was induced by constriction of the thoracic portion of vena cava inferior. Two-three days after the operation renal function was studied and the activity of succinate dehydrogenase and Na+K+-ATPase in the cells of the renal tubules was determined cytochemically. On infusion of 0.9% NaCl solution into the stomach, the filtration in the \"caval\" rats did not change whereas the excretion of sodium and its concentration in the urine were much lower than in the sham operated rats. At the same time, the activity of Na+K+-ATPase and succinate dehydrogenase in the \"caval\" rats increased in the cells of the proximal tubule, diminished in Henle's loop, and remained unchanged in the cells of the distal convoluted tubule. Comparison of the results of functional and cytochemical study of the kidneys in caval rats allows the conclusion that intensified proximal reabsorption may be the main cause of antinatriuresis in these animals. The lesser load experienced by the distal segment promotes fuller reabsorption of sodium in this part of the nephron too.", "contents": "[Kidney function and Na+-K+-ATPase and succinate dehydrogenase activity in the cells of the renal tubules of rats with constriction of the thoracic portion of the vena cava inferior]. Circulatory insufficiency in rats was induced by constriction of the thoracic portion of vena cava inferior. Two-three days after the operation renal function was studied and the activity of succinate dehydrogenase and Na+K+-ATPase in the cells of the renal tubules was determined cytochemically. On infusion of 0.9% NaCl solution into the stomach, the filtration in the \"caval\" rats did not change whereas the excretion of sodium and its concentration in the urine were much lower than in the sham operated rats. At the same time, the activity of Na+K+-ATPase and succinate dehydrogenase in the \"caval\" rats increased in the cells of the proximal tubule, diminished in Henle's loop, and remained unchanged in the cells of the distal convoluted tubule. Comparison of the results of functional and cytochemical study of the kidneys in caval rats allows the conclusion that intensified proximal reabsorption may be the main cause of antinatriuresis in these animals. The lesser load experienced by the distal segment promotes fuller reabsorption of sodium in this part of the nephron too."}
{"id": "PMID:218037", "title": "[Sodium-potassium-adenosine triphosphatase-activity in red cell ghosts of patients with essential hypertension (author's transl)].", "content": "Increased sodium concentration and high influx of Na22 are reported in erythrocytes of patients with essential hypertension. It was speculated, that these findings are due to a disturbed transport for sodium across red cell membranes. We found a significantly increased activity of the ouabainsensitive Na-K-ATP'ase in red cell ghosts of 27 patients with essential hypertension compaired with 32 normotensive controls. There existed no difference in Mg-ATP'ase-activity between the two groups. These findings suggest an increased activity of the Na-pump in red cell membranes of patients with essential hypertension.", "contents": "[Sodium-potassium-adenosine triphosphatase-activity in red cell ghosts of patients with essential hypertension (author's transl)]. Increased sodium concentration and high influx of Na22 are reported in erythrocytes of patients with essential hypertension. It was speculated, that these findings are due to a disturbed transport for sodium across red cell membranes. We found a significantly increased activity of the ouabainsensitive Na-K-ATP'ase in red cell ghosts of 27 patients with essential hypertension compaired with 32 normotensive controls. There existed no difference in Mg-ATP'ase-activity between the two groups. These findings suggest an increased activity of the Na-pump in red cell membranes of patients with essential hypertension."}
{"id": "PMID:218052", "title": "Glomus tumor of the middle ear: origin, symptomatology, and treatment.", "content": "The glomus tumor is considered to be the most common of all tumors that involve the middle ear. This report defines the glomus tumor and discusses the symptomatology of the tumor with respect to the various developmental courses it may follow. Forty clinical cases of glomus tumor are reviewed, with emphasis upon the incidence of the tumor and its symptoms, including the audiological manifestations noted in this series of cases. Current medical management of the glomus tumor recommends surgical removal of the lesion when possible; however, irradiation and embolization of the tumor may also be considered when its invasion into surrounding structures has been extensive. The pathology and its treatment may have marked temporary or permanent effects upon the hearing of the patient, and the importance of ongoing audiological management is therefore emphasized.", "contents": "Glomus tumor of the middle ear: origin, symptomatology, and treatment. The glomus tumor is considered to be the most common of all tumors that involve the middle ear. This report defines the glomus tumor and discusses the symptomatology of the tumor with respect to the various developmental courses it may follow. Forty clinical cases of glomus tumor are reviewed, with emphasis upon the incidence of the tumor and its symptoms, including the audiological manifestations noted in this series of cases. Current medical management of the glomus tumor recommends surgical removal of the lesion when possible; however, irradiation and embolization of the tumor may also be considered when its invasion into surrounding structures has been extensive. The pathology and its treatment may have marked temporary or permanent effects upon the hearing of the patient, and the importance of ongoing audiological management is therefore emphasized."}
{"id": "PMID:218061", "title": "Lymphatic dynamics of liver by hepatic lymphography using lipiodol ultra fluid.", "content": "Hepatic lymphography by intra-parenchymal injection of four to ten millilitres (ml) of lipiodol ultrafluid, our modification of functional hepatography, performed on sixty one patients helped study lymphatic dynamics of liver. In conditions associated with significant hepatic venous outflow obstructions, such as hepatic cirrhosis, inflammatory diseases of liver and primary or secondary malignant lesions of the liver, this study delineated liver lymphatics and portal and para aortic lymph nodes. In one case mediastinal nodes were also delineated by flow of lipiodol from the bare area of the liver via trans-diaphragmatic and pleural lymphatic. The lymphangio-architecture of the opacified nodes depicted the nature of pathology inflicting them and the liver. Lipiodol in the lymphatic system, staying longer than the freely diffusible aqueous contrast, provided more detail and better information.", "contents": "Lymphatic dynamics of liver by hepatic lymphography using lipiodol ultra fluid. Hepatic lymphography by intra-parenchymal injection of four to ten millilitres (ml) of lipiodol ultrafluid, our modification of functional hepatography, performed on sixty one patients helped study lymphatic dynamics of liver. In conditions associated with significant hepatic venous outflow obstructions, such as hepatic cirrhosis, inflammatory diseases of liver and primary or secondary malignant lesions of the liver, this study delineated liver lymphatics and portal and para aortic lymph nodes. In one case mediastinal nodes were also delineated by flow of lipiodol from the bare area of the liver via trans-diaphragmatic and pleural lymphatic. The lymphangio-architecture of the opacified nodes depicted the nature of pathology inflicting them and the liver. Lipiodol in the lymphatic system, staying longer than the freely diffusible aqueous contrast, provided more detail and better information."}
{"id": "PMID:218066", "title": "Activation of sterol ester hydrolase of bovine corpus luteum by N6,O2'-dibutyryl cyclic adenosine 3':5'-phosphate.", "content": "The direct activation of sterol ester hydrolase (E.C. 3.1.1.13) in homogenates of bovine corpus luteum by N6O2'-dibutyryl cyclic adenosine 3':5'-phosphate, (dibutyryl cAMP), adenosine triphosphate (ATP), and Mg2+ has been demonstrated. Variability in the extent of activation by the additions was minimized by homogenization of the tissue in 5 mM Mg2+'. Baseline sterol ester hydrolase activity was primarily associated with the 105,000 X g soluble fraction, and significant activation of the enzyme preparation preincubated with dibutyryl cAMP, ATP and Mg2+ occurred within the first 15 min, prior to addition of substrate. A requirement for protein kinase in the system was demonstrated by blocking the cofactor-dependent enzyme activation with commercial protein kinase inhibitor.", "contents": "Activation of sterol ester hydrolase of bovine corpus luteum by N6,O2'-dibutyryl cyclic adenosine 3':5'-phosphate. The direct activation of sterol ester hydrolase (E.C. 3.1.1.13) in homogenates of bovine corpus luteum by N6O2'-dibutyryl cyclic adenosine 3':5'-phosphate, (dibutyryl cAMP), adenosine triphosphate (ATP), and Mg2+ has been demonstrated. Variability in the extent of activation by the additions was minimized by homogenization of the tissue in 5 mM Mg2+'. Baseline sterol ester hydrolase activity was primarily associated with the 105,000 X g soluble fraction, and significant activation of the enzyme preparation preincubated with dibutyryl cAMP, ATP and Mg2+ occurred within the first 15 min, prior to addition of substrate. A requirement for protein kinase in the system was demonstrated by blocking the cofactor-dependent enzyme activation with commercial protein kinase inhibitor."}
{"id": "PMID:218067", "title": "Distribution of high density and other lipoproteins in selected LRC prevalence study populations: a brief survey.", "content": "Selected lipid and lipoprotein data from the Lipid Research Clinics (LRC) Prevalence Study are presented, with particular emphasis given to high-density lipoprotein (HDL) values. Cross-sectional age- and sex-specific mean values are shown for 7007 white participants in the ten North American LRCs. Comparisons are drawn for males and females (including the pediatric group) and for females using or not using sex hormones. The US-USSR Collaborative Program is summarized, and selected comparisons are noted for the Soviet and United States samples.", "contents": "Distribution of high density and other lipoproteins in selected LRC prevalence study populations: a brief survey. Selected lipid and lipoprotein data from the Lipid Research Clinics (LRC) Prevalence Study are presented, with particular emphasis given to high-density lipoprotein (HDL) values. Cross-sectional age- and sex-specific mean values are shown for 7007 white participants in the ten North American LRCs. Comparisons are drawn for males and females (including the pediatric group) and for females using or not using sex hormones. The US-USSR Collaborative Program is summarized, and selected comparisons are noted for the Soviet and United States samples."}
{"id": "PMID:218069", "title": "HDL-cholesterol levels in the Multiple Risk Factor Intervention Trial (MRFIT) by the MRFIT Research Group 1,2.", "content": "Preliminary data from the Multiple Risk Factor Intervention Trial (MRFIT) have been examined for evidence that the program has an influence on plasma HDL-cholesterol. The overall mean level of this lipoprotein in the initial cohort of 1,084 men was not altered by two years of participation in this risk factor reduction project. However, changes did occur, both upwards and downwards, in some individuals. There were significant negative associations between change in HDL-cholesterol and changes in body mass, VLDL-cholesterol, LDL-cholesterol, and serum thiocyanate (a measure of cigarette smoking exposure); and there was a small positive association with change in reported alcohol intake. Multiple regression analysis revealed each of these associations to be independent of the others. The fat-controlled diet designed to lower total serum cholesterol did not decrease HDL-cholesterol levels. We conclude that conventional risk reduction programs are not likely to lower circulating HDL-cholesterol, and that program components such as weight reduction and smoking cessation may increase the levels.", "contents": "HDL-cholesterol levels in the Multiple Risk Factor Intervention Trial (MRFIT) by the MRFIT Research Group 1,2. Preliminary data from the Multiple Risk Factor Intervention Trial (MRFIT) have been examined for evidence that the program has an influence on plasma HDL-cholesterol. The overall mean level of this lipoprotein in the initial cohort of 1,084 men was not altered by two years of participation in this risk factor reduction project. However, changes did occur, both upwards and downwards, in some individuals. There were significant negative associations between change in HDL-cholesterol and changes in body mass, VLDL-cholesterol, LDL-cholesterol, and serum thiocyanate (a measure of cigarette smoking exposure); and there was a small positive association with change in reported alcohol intake. Multiple regression analysis revealed each of these associations to be independent of the others. The fat-controlled diet designed to lower total serum cholesterol did not decrease HDL-cholesterol levels. We conclude that conventional risk reduction programs are not likely to lower circulating HDL-cholesterol, and that program components such as weight reduction and smoking cessation may increase the levels."}
{"id": "PMID:218070", "title": "Serum high density lipoprotein and its relationship to cardiovascular disease risk factor variables in children--the Bogalusa heart study.", "content": "Serum high density lipoprotein is increasingly recognized as a negative risk for cardiovascular disease. The distribution and interrelationship of serum lipids, lipoproteins, anthropometric measurements and blood pressures were determined in some 5,000 children. Children had mean +/- S.D. alpha-lipoprotein cholesterol levels (mg/100 ml) of 36 +/- 15 at birth, 51 +/- 22 at 6 mo, 53 +/- 18 at 1 yr, 60 +/- 19 at preschool age (2 1/2-5 1/2 yr) and 68 +/- 22 at school age (5-14 yr), reflecting a sharp increase in alpha-lipoprotein between birth and school-age years, when these levels remained relatively stable through age 14. Although white children tended to have higher levels of total cholesterol and alpha-lipoprotein at birth than black children, during childhood this trend was reversed and the differences were pronounced in school-age children (p less than 0.0001). Unlike in adulthood, boys had slightly higher levels of alpha-lipoprotein than girls. The alpha-lipoprotein was negatively correlated with pre-beta-lipoprotein and to a lesser extent with beta-lipoprotein classes. There was an inverse relationship between alpha-lipoprotein and obesity with a consistently significant relationship (p less than 0.01) in older children (10-14 yr). Children with higher levels of alpha-lipoprotein have lower levels of blood pressure, beta-lipoprotein and a lower obesity index.", "contents": "Serum high density lipoprotein and its relationship to cardiovascular disease risk factor variables in children--the Bogalusa heart study. Serum high density lipoprotein is increasingly recognized as a negative risk for cardiovascular disease. The distribution and interrelationship of serum lipids, lipoproteins, anthropometric measurements and blood pressures were determined in some 5,000 children. Children had mean +/- S.D. alpha-lipoprotein cholesterol levels (mg/100 ml) of 36 +/- 15 at birth, 51 +/- 22 at 6 mo, 53 +/- 18 at 1 yr, 60 +/- 19 at preschool age (2 1/2-5 1/2 yr) and 68 +/- 22 at school age (5-14 yr), reflecting a sharp increase in alpha-lipoprotein between birth and school-age years, when these levels remained relatively stable through age 14. Although white children tended to have higher levels of total cholesterol and alpha-lipoprotein at birth than black children, during childhood this trend was reversed and the differences were pronounced in school-age children (p less than 0.0001). Unlike in adulthood, boys had slightly higher levels of alpha-lipoprotein than girls. The alpha-lipoprotein was negatively correlated with pre-beta-lipoprotein and to a lesser extent with beta-lipoprotein classes. There was an inverse relationship between alpha-lipoprotein and obesity with a consistently significant relationship (p less than 0.01) in older children (10-14 yr). Children with higher levels of alpha-lipoprotein have lower levels of blood pressure, beta-lipoprotein and a lower obesity index."}
{"id": "PMID:218072", "title": "Membrane-bound phospholipid desaturases.", "content": "This review covers studies on membrane-bound phospholipid desaturases in yeast and rat liver carried out in this laboratory. In yeast the desaturase system was shown to effect the direct desaturation of dioleoyl-lecithin to dilinoleoyl-lecithin. In rat liver the desaturase was capable of converting 2-eicosatrienoyl-lecithin to 2-arachidonoyl-lecithin. Both systems required reduced pyridine nucleotides, O2 and cytochrome b5. Eicosatrienoyl-lecithin desaturase along with eicosatrienoyl-CoA desaturase of rat liver microsomes was solubilized with detergents and purified 7-8-fold from the microsomal pellets. Both activities were reconstituted in the presence of deoxycholate on addition of the other components of the cytochrome b5-electron transport chain (cytochrome b5 and NADH-cytochrome b5 reductase) to the solubilized desaturase; addition of lecithin further stimulated the activities. The demonstration of desaturation of eicosatrienoyl-lecithin by a solubilized and partially purified desaturase provides strong evidence for the direct desaturation of the lecithin substrate without prior conversion to the acyl-CoA thiolester.", "contents": "Membrane-bound phospholipid desaturases. This review covers studies on membrane-bound phospholipid desaturases in yeast and rat liver carried out in this laboratory. In yeast the desaturase system was shown to effect the direct desaturation of dioleoyl-lecithin to dilinoleoyl-lecithin. In rat liver the desaturase was capable of converting 2-eicosatrienoyl-lecithin to 2-arachidonoyl-lecithin. Both systems required reduced pyridine nucleotides, O2 and cytochrome b5. Eicosatrienoyl-lecithin desaturase along with eicosatrienoyl-CoA desaturase of rat liver microsomes was solubilized with detergents and purified 7-8-fold from the microsomal pellets. Both activities were reconstituted in the presence of deoxycholate on addition of the other components of the cytochrome b5-electron transport chain (cytochrome b5 and NADH-cytochrome b5 reductase) to the solubilized desaturase; addition of lecithin further stimulated the activities. The demonstration of desaturation of eicosatrienoyl-lecithin by a solubilized and partially purified desaturase provides strong evidence for the direct desaturation of the lecithin substrate without prior conversion to the acyl-CoA thiolester."}
{"id": "PMID:218083", "title": "[Effect of phosphate and glucose on the growth kinetics and phsophohydrolase activity of Penicillium brevi-compactum].", "content": "The kinetics of growth of Penicillium brevi-compactum and the activity of exocellular phosphohydrolases were studied on media with different concentrations of glucose and phosphate. Exocellular phosphohydrolases were synthesized when the growth was decelerated due to the deficiency of phosphate rather than that of glucose. These enzymes were not synthesized if the growth was not limited by phosphate. Synthesis of exocellular phosphohydrolases was repressed by phosphate when the growth was limited by glucose. Apparently, a complex of exocellular phosphohydrolases is synthesized by the culture if its growth is limited by phosphate.", "contents": "[Effect of phosphate and glucose on the growth kinetics and phsophohydrolase activity of Penicillium brevi-compactum]. The kinetics of growth of Penicillium brevi-compactum and the activity of exocellular phosphohydrolases were studied on media with different concentrations of glucose and phosphate. Exocellular phosphohydrolases were synthesized when the growth was decelerated due to the deficiency of phosphate rather than that of glucose. These enzymes were not synthesized if the growth was not limited by phosphate. Synthesis of exocellular phosphohydrolases was repressed by phosphate when the growth was limited by glucose. Apparently, a complex of exocellular phosphohydrolases is synthesized by the culture if its growth is limited by phosphate."}
{"id": "PMID:218084", "title": "[Alternative oxidation pathways in the respiratory chain of Brevibacterium flavum].", "content": "A scheme is proposed for the branched respiratory chain in Brevibacterium flavum 22 LD. Three branching sites in the main electron transport pathway are suggested: at the initial stage of NADH2 oxidation (before menaquinone) and at the levels of cytochromes b and c. Up to 40% out of the total oxygen is consumed in the NADH2-dependent alternative oxidative pathway in the presence of 5.10(-3) M cyanide or after the near UV treatment. This bypass differs from the main electron flow with a lower P/O ratio. Exogenous NADH2 catalyses the univalent reduction of oxygen through superoxide production in the bacterial membranes. Alternative oxidation pathways are discussed regarding their regulatory role in the bacterial energy metabolism.", "contents": "[Alternative oxidation pathways in the respiratory chain of Brevibacterium flavum]. A scheme is proposed for the branched respiratory chain in Brevibacterium flavum 22 LD. Three branching sites in the main electron transport pathway are suggested: at the initial stage of NADH2 oxidation (before menaquinone) and at the levels of cytochromes b and c. Up to 40% out of the total oxygen is consumed in the NADH2-dependent alternative oxidative pathway in the presence of 5.10(-3) M cyanide or after the near UV treatment. This bypass differs from the main electron flow with a lower P/O ratio. Exogenous NADH2 catalyses the univalent reduction of oxygen through superoxide production in the bacterial membranes. Alternative oxidation pathways are discussed regarding their regulatory role in the bacterial energy metabolism."}
{"id": "PMID:218087", "title": "Nephroblastoma (Wilms tumor): tubule density and prognosis.", "content": "Relative differences in tubules density of the primary tumors have been suggested to be prognostically useful in nephroblastoma (Wilms tumor). Forty cases from our institution were retrospectively graded according to tubule density. There were significant differences in disease-free survivals between histologic grades. When compared to other clinical and pathologic staging criteria, tubule density was not more useful prognostically than the staging systems tested. However, when used in conjunction with clinical or pathologic stage, tumor grade improved prognostic sensitivity. Regardless of grade or stage, patients less than 24-months-old at diagnosis had better disease-free survival.", "contents": "Nephroblastoma (Wilms tumor): tubule density and prognosis. Relative differences in tubules density of the primary tumors have been suggested to be prognostically useful in nephroblastoma (Wilms tumor). Forty cases from our institution were retrospectively graded according to tubule density. There were significant differences in disease-free survivals between histologic grades. When compared to other clinical and pathologic staging criteria, tubule density was not more useful prognostically than the staging systems tested. However, when used in conjunction with clinical or pathologic stage, tumor grade improved prognostic sensitivity. Regardless of grade or stage, patients less than 24-months-old at diagnosis had better disease-free survival."}
{"id": "PMID:218085", "title": "[Localization of hydrogenase in the cells of the thermophilic hydrogen bacterium, Pseudomonas thermophila].", "content": "Spheroplasts that were osmotically stable in 0.2M Tris-HCl--0.02M EDTA were prepared from the autotrophically grown cells of Pseudomonas thermophila K-2. The spheroplasts possessed 90--95% of the hydrogenase activity of the whole cells. The half-life time of hydrogenase in the spheroplasts at 80 degrees C was 8.5 min. A spectrophotometric technique was developed for determining the membrane-bound hydrogenase in the presence of sulfhydryl compounds with methylene blue as electron acceptor. The maximal specific activity of hydrogenase in extracts prepared in the anaerobic conditions in the presence of dithiothreitol and Mg2+ and Mn2+ ions was 10 +/- 3 units per 1 mg of protein, which closely corresponded with the activity of hydrogenase in the whole cells. Almost all activity of hydrogenase assayed with methylene blue was localized in the membrane fraction. The activity of soluble NAD-specific hydrogenase was not detected. Large particles located in 60-70% sucrose had the highest hydrogenase activity upon fractionation in a continuous sucrose concentration gradient. The second, lower peak of the hydrogenase activity was detected in fractions of 40--50% sucrose. As was found by electron microscopy, the size of membrane vesicles with the hydrogenase activity varied within the range of 68--156 nm. The membrane preparations possessed the activity of NADH-dehydrogenase, NADH-oxidase and succinate dehydrogenase as well.", "contents": "[Localization of hydrogenase in the cells of the thermophilic hydrogen bacterium, Pseudomonas thermophila]. Spheroplasts that were osmotically stable in 0.2M Tris-HCl--0.02M EDTA were prepared from the autotrophically grown cells of Pseudomonas thermophila K-2. The spheroplasts possessed 90--95% of the hydrogenase activity of the whole cells. The half-life time of hydrogenase in the spheroplasts at 80 degrees C was 8.5 min. A spectrophotometric technique was developed for determining the membrane-bound hydrogenase in the presence of sulfhydryl compounds with methylene blue as electron acceptor. The maximal specific activity of hydrogenase in extracts prepared in the anaerobic conditions in the presence of dithiothreitol and Mg2+ and Mn2+ ions was 10 +/- 3 units per 1 mg of protein, which closely corresponded with the activity of hydrogenase in the whole cells. Almost all activity of hydrogenase assayed with methylene blue was localized in the membrane fraction. The activity of soluble NAD-specific hydrogenase was not detected. Large particles located in 60-70% sucrose had the highest hydrogenase activity upon fractionation in a continuous sucrose concentration gradient. The second, lower peak of the hydrogenase activity was detected in fractions of 40--50% sucrose. As was found by electron microscopy, the size of membrane vesicles with the hydrogenase activity varied within the range of 68--156 nm. The membrane preparations possessed the activity of NADH-dehydrogenase, NADH-oxidase and succinate dehydrogenase as well."}
{"id": "PMID:218088", "title": "[Clinico-statistical study of the period of formation and mineralization of the 3d molar].", "content": "Examination of 540 Italians indicated that the third molar may form between the 6th and 13th year of life. The statistical possibilities of forecasting agenesis of this tooth at different periods of life are evaluated in this light of the data obtained.", "contents": "[Clinico-statistical study of the period of formation and mineralization of the 3d molar]. Examination of 540 Italians indicated that the third molar may form between the 6th and 13th year of life. The statistical possibilities of forecasting agenesis of this tooth at different periods of life are evaluated in this light of the data obtained."}
{"id": "PMID:218095", "title": "[Absorption and magnetic circular dichroism spectra of heme proteins in nonequilibrium states. IV. Cytochrome c and its derivatives].", "content": "Absorption and magnetic circular dichroism spectra (77 degrees K) of nonequilibrium cytochrome c and its derivatives reduced by thermolysed electrons was studied. The low temperature spectral characteristics of reduced cytochrome c (pH 7.0, 1.6 and 10.0), dimer, carboxymetylated and formylated derivatives at netral and acid pH, also fluoride complexes differ from the characteristics of equilibrium reduced forms. The temperature increase (up to 177 degrees K) induces relaxation of nonequilibrium states. These effects are due to structural differences in the heme vicinity of the reduced and oxidized forms.", "contents": "[Absorption and magnetic circular dichroism spectra of heme proteins in nonequilibrium states. IV. Cytochrome c and its derivatives]. Absorption and magnetic circular dichroism spectra (77 degrees K) of nonequilibrium cytochrome c and its derivatives reduced by thermolysed electrons was studied. The low temperature spectral characteristics of reduced cytochrome c (pH 7.0, 1.6 and 10.0), dimer, carboxymetylated and formylated derivatives at netral and acid pH, also fluoride complexes differ from the characteristics of equilibrium reduced forms. The temperature increase (up to 177 degrees K) induces relaxation of nonequilibrium states. These effects are due to structural differences in the heme vicinity of the reduced and oxidized forms."}
{"id": "PMID:218100", "title": "The induction of dominant lethal mutations in Tilapia mossambica by alkane sulphonic esters.", "content": "A serial mating system has been used to enable study of the effect of chemical mutagens in Tilapia mossambica. Embryopathies incompatible with survival are attributed to dominant lethal mutations induced in developing male germ cells by methyl methanesulphonate and the isomeric forms of dimethyl-myleran.", "contents": "The induction of dominant lethal mutations in Tilapia mossambica by alkane sulphonic esters. A serial mating system has been used to enable study of the effect of chemical mutagens in Tilapia mossambica. Embryopathies incompatible with survival are attributed to dominant lethal mutations induced in developing male germ cells by methyl methanesulphonate and the isomeric forms of dimethyl-myleran."}
{"id": "PMID:218107", "title": "Update of naltrexone treatment.", "content": "To summarize, then, our work with naltrexone in a multi-modality treatment program indicates that it appeals to about 5-10 percent of narcotic addicts--those who conciously want to obtain drug-free status. It does significantly attentuate the effect of narcotics to the extent that they lose their reinforcing properties, and it has minimal side effects. Although we treated a self-selected population, it is noteworthy that about 10 percent of those who remained on naltrexone for more than a week were still opiate free 6 months after cessation of treatment. For some it appeared to be a turning point in their lives. It was the first time in years that they could live in their neighborhood and not be either intoxicated or occupied with the pursuit of narcotics. Our behavioral studies have identified a number of conditioned psychophysiological responses associated with the self-injection ritual. So far, although we have succeeded in extinguishing some of these responses, this has not resulted in an improved clinical outcome. We are currently working on more comprehensive behavioral treatments, but the clinical significance of these conditioned responses is uncertain at present.", "contents": "Update of naltrexone treatment. To summarize, then, our work with naltrexone in a multi-modality treatment program indicates that it appeals to about 5-10 percent of narcotic addicts--those who conciously want to obtain drug-free status. It does significantly attentuate the effect of narcotics to the extent that they lose their reinforcing properties, and it has minimal side effects. Although we treated a self-selected population, it is noteworthy that about 10 percent of those who remained on naltrexone for more than a week were still opiate free 6 months after cessation of treatment. For some it appeared to be a turning point in their lives. It was the first time in years that they could live in their neighborhood and not be either intoxicated or occupied with the pursuit of narcotics. Our behavioral studies have identified a number of conditioned psychophysiological responses associated with the self-injection ritual. So far, although we have succeeded in extinguishing some of these responses, this has not resulted in an improved clinical outcome. We are currently working on more comprehensive behavioral treatments, but the clinical significance of these conditioned responses is uncertain at present."}
{"id": "PMID:218115", "title": "[Chemical mechanism of the effect of alcohol].", "content": "The formation of tetrahydro-isoquinoline alkaloids in human and animal metabolisms subsequent to alcohol consumption is reported. The spectrum of identified products ranges from simple structures such as salsolinol to the complicated skeleton of protoberberines. These substances, hitherto found exclusively in plants, interfere with the biosynthesis, biodegradation and neurotransmission of the structurally closely related biogenic amines from which they are formed, and thus affect the vegetative nervous system.", "contents": "[Chemical mechanism of the effect of alcohol]. The formation of tetrahydro-isoquinoline alkaloids in human and animal metabolisms subsequent to alcohol consumption is reported. The spectrum of identified products ranges from simple structures such as salsolinol to the complicated skeleton of protoberberines. These substances, hitherto found exclusively in plants, interfere with the biosynthesis, biodegradation and neurotransmission of the structurally closely related biogenic amines from which they are formed, and thus affect the vegetative nervous system."}
{"id": "PMID:218118", "title": "Prostacyclin (PGI2) decreases the cyclic AMP level in coronary arteries.", "content": "The effects of prostacyclin (PGI2) on vascular tension and cAMP content were measured in isolated bovine coronary artery strips. 3 nM PGI2 did not alter the tension but diminished the cAMP content by 56% of the control level (P less than 0.005). 30 and 300 nM PGI2 diminished the tension and further reduced the cAMP content, which amounted to only 5% of the control at 300 nM PGI2. These results are in contrast to the increase in cAMP level by PGI2 in blood platelets and might indicate a different mechanism of action of PGI2 in platelets and vascular tissue.", "contents": "Prostacyclin (PGI2) decreases the cyclic AMP level in coronary arteries. The effects of prostacyclin (PGI2) on vascular tension and cAMP content were measured in isolated bovine coronary artery strips. 3 nM PGI2 did not alter the tension but diminished the cAMP content by 56% of the control level (P less than 0.005). 30 and 300 nM PGI2 diminished the tension and further reduced the cAMP content, which amounted to only 5% of the control at 300 nM PGI2. These results are in contrast to the increase in cAMP level by PGI2 in blood platelets and might indicate a different mechanism of action of PGI2 in platelets and vascular tissue."}
{"id": "PMID:218119", "title": "Dehydro-digitoxosides of digitoxigenin and digoxigenin: binding to beef heart (Na+ + K+)-ATPase in relation to unchanged digitoxosides.", "content": "Dehydro-digitoxosides are metabolites of digitalis glycosides. In order to study their possible biological activity their affinity to (Na+ + K+)-activated ATPase was determined and compared with unchanged glycosides. Based on the dissociation constants of glycoside-enzyme-complexes, the affinity of the dehydro-digitoxosides ranged in the same order of magnitude as that of the native glycosides. Comparing mono-, bis-, and tris-digitoxosides of digitoxigenin (dt-1, dt-2, dt-3) and of digoxin (dg-1, dg-2, dg-3) with the corresponding dehydrodigitoxosides (3'-dehydro-dt-1, 9'-dehydro-dt-2, 15'-dehydro-dt3, 3'-dehydro-dg-1 and 9'-dehydro-dg-2, respectively) the dehydro-digitoxosides had lower affinities to the enzyme. The highest dissociation constants (KD) were found for 3'-dehydro-dt-1 and 3'-dehydro-dg-1. The half maximal inhibition of (Na+ + K+)-ATPase activity (I50) coresponded to affinity measurements in all but two cases: dehydro-dt-3 and dehydro-dt-2 showed very low I50 values.", "contents": "Dehydro-digitoxosides of digitoxigenin and digoxigenin: binding to beef heart (Na+ + K+)-ATPase in relation to unchanged digitoxosides. Dehydro-digitoxosides are metabolites of digitalis glycosides. In order to study their possible biological activity their affinity to (Na+ + K+)-activated ATPase was determined and compared with unchanged glycosides. Based on the dissociation constants of glycoside-enzyme-complexes, the affinity of the dehydro-digitoxosides ranged in the same order of magnitude as that of the native glycosides. Comparing mono-, bis-, and tris-digitoxosides of digitoxigenin (dt-1, dt-2, dt-3) and of digoxin (dg-1, dg-2, dg-3) with the corresponding dehydrodigitoxosides (3'-dehydro-dt-1, 9'-dehydro-dt-2, 15'-dehydro-dt3, 3'-dehydro-dg-1 and 9'-dehydro-dg-2, respectively) the dehydro-digitoxosides had lower affinities to the enzyme. The highest dissociation constants (KD) were found for 3'-dehydro-dt-1 and 3'-dehydro-dg-1. The half maximal inhibition of (Na+ + K+)-ATPase activity (I50) coresponded to affinity measurements in all but two cases: dehydro-dt-3 and dehydro-dt-2 showed very low I50 values."}
{"id": "PMID:218120", "title": "Presynaptic inhibitory actions of 2-substituted adenosine derivatives on neurotransmission in rat vas deferens: effects of inhibitors of adenosine uptake and deamination.", "content": "In the isolated rat vas deferens, various 2-substituted adenosine derivatives and adenosine inhibited contractions elicited by field stimulation but had little effect on responses to exogenous noradrenaline. 2-Chloroadenosine, 2-bromoadenosine, 2-hydroxyadenosine and 2-fluoroadenosine were all more potent than adenosine. Theophylline antagonized the action of the 2-substituted derivatives. The inhibitory action of adenosine was potentiated by dipyridamole, 2-amino-6-[(2-hydroxy-5-nitro)benzylthio]-9-beta-D-ribofuranosylpurine (HNBTG) or 2'-deoxycoformycin while that of 2-choloroadenosine was not altered by any of these drugs or by phenoxybenzamine, atropine or indomethacin. Pretreatment of the vas deferens with both HNBTG and 2'-deoxycoformycin eliminated the difference in inhibitory potency between adenosine and 2-chloroadenosine. These results indicate that 2-substituted adenosine derivatives, like adenosine, produce inhibition of transmission by acting on a presynaptic site which can be blocked by theophylline. The high apparent potency of 2-chloroadenosine compared to adenosine appears to be due to the former being neither taken up nor deaminated, while the apparent potency of adenosine is masked by uptake and deamination in this tissue.", "contents": "Presynaptic inhibitory actions of 2-substituted adenosine derivatives on neurotransmission in rat vas deferens: effects of inhibitors of adenosine uptake and deamination. In the isolated rat vas deferens, various 2-substituted adenosine derivatives and adenosine inhibited contractions elicited by field stimulation but had little effect on responses to exogenous noradrenaline. 2-Chloroadenosine, 2-bromoadenosine, 2-hydroxyadenosine and 2-fluoroadenosine were all more potent than adenosine. Theophylline antagonized the action of the 2-substituted derivatives. The inhibitory action of adenosine was potentiated by dipyridamole, 2-amino-6-[(2-hydroxy-5-nitro)benzylthio]-9-beta-D-ribofuranosylpurine (HNBTG) or 2'-deoxycoformycin while that of 2-choloroadenosine was not altered by any of these drugs or by phenoxybenzamine, atropine or indomethacin. Pretreatment of the vas deferens with both HNBTG and 2'-deoxycoformycin eliminated the difference in inhibitory potency between adenosine and 2-chloroadenosine. These results indicate that 2-substituted adenosine derivatives, like adenosine, produce inhibition of transmission by acting on a presynaptic site which can be blocked by theophylline. The high apparent potency of 2-chloroadenosine compared to adenosine appears to be due to the former being neither taken up nor deaminated, while the apparent potency of adenosine is masked by uptake and deamination in this tissue."}
{"id": "PMID:218124", "title": "A characterization of the nature and control of cellular allograft rejection.", "content": "The mechanism of cellular rejection has been analyzed. The cells infiltrating rat cardiac allografts have been recovered and identified. An important role for cytotoxic T lymphocytes in cellular rejection has been discerned. The entrapment of cytotoxic T lymphocytes within rejecting grafts is not rigorously dependent upon antigen recognition. The cellular processes by which cytotoxic T lymphocytes destroy target cells have been determined in part. Cellular levels of the 3',5' cyclic nucleotides modulate this process. Elevations in cellular levels of cyclic AMP inhibit cytotoxicity whereas increased cyclic GMP stimulates augmented cytotoxicity.", "contents": "A characterization of the nature and control of cellular allograft rejection. The mechanism of cellular rejection has been analyzed. The cells infiltrating rat cardiac allografts have been recovered and identified. An important role for cytotoxic T lymphocytes in cellular rejection has been discerned. The entrapment of cytotoxic T lymphocytes within rejecting grafts is not rigorously dependent upon antigen recognition. The cellular processes by which cytotoxic T lymphocytes destroy target cells have been determined in part. Cellular levels of the 3',5' cyclic nucleotides modulate this process. Elevations in cellular levels of cyclic AMP inhibit cytotoxicity whereas increased cyclic GMP stimulates augmented cytotoxicity."}
{"id": "PMID:218125", "title": "Post-obstructive nephropathy in the rat: relationship between NA-K-ATPase activity and renal function.", "content": "Na-K-ATPase activity and renal function were compared in rats studied after relief of 24 h of unilateral or bilateral ureteral ligation (UUL or BUL), that is, in the absence or presence of post-obstructive diuresis. Na-K-ATPase activity in the outer medulla of the rat kidney after relief of UUL was not significantly altered immediately but was markedly reduced 1 and 3 days post-obstruction. The decrease in medullary Na-K-ATPase activity was not significantly different from that observed after relief of BUL. These results indicate that decreased Na-K-ATPase activity in the post-obstructive kidney is not responsible for post-obstructive diuresis and is not due to uremia, but is a local phenomenon which is probably secondary to altered renal structure or function. It may be due to decreased filtered sodium load or direct tubular damage, but other data suggests that the decreased medullary solute concentration gradient in the post-obstructive kidney (UUL or BUL) may influence Na-K-ATPase activity which, in turn, contributes to the decreased ability to conserve sodium and water.", "contents": "Post-obstructive nephropathy in the rat: relationship between NA-K-ATPase activity and renal function. Na-K-ATPase activity and renal function were compared in rats studied after relief of 24 h of unilateral or bilateral ureteral ligation (UUL or BUL), that is, in the absence or presence of post-obstructive diuresis. Na-K-ATPase activity in the outer medulla of the rat kidney after relief of UUL was not significantly altered immediately but was markedly reduced 1 and 3 days post-obstruction. The decrease in medullary Na-K-ATPase activity was not significantly different from that observed after relief of BUL. These results indicate that decreased Na-K-ATPase activity in the post-obstructive kidney is not responsible for post-obstructive diuresis and is not due to uremia, but is a local phenomenon which is probably secondary to altered renal structure or function. It may be due to decreased filtered sodium load or direct tubular damage, but other data suggests that the decreased medullary solute concentration gradient in the post-obstructive kidney (UUL or BUL) may influence Na-K-ATPase activity which, in turn, contributes to the decreased ability to conserve sodium and water."}
{"id": "PMID:218126", "title": "The influence of brain cytosol on RNA synthesis and RNA products of isolated mouse brain nuclei.", "content": "The incubation of isolated nuclei obtained from 10-day-old mouse brain in the presence of brain cell cytosol resulted in an increase in the synthesis of RNA. Under conditions of saturating concentrations of nucleoside triphosphates, the influence of cytosol could not be duplicated by the addition of cyclic nucleotides. The stimulatory activity of cytosol on brain nuclear RNA synthesis could not be attributed to either alterations in the permeability of the nuclear envelope or an increased uptake of radioactively-labeled precursors. Sucrose gradient analysis demonstrated that the RNA products synthesized by nuclei isolated from 10-day-old and adult mouse brain were of a relatively low molecular weight. However, the addition of cytosol resulted in a significant increase in the size of the RNA transcripts. In contrast to the observations with 10-day-old and adult brain nuclei, the RNA from 2-day-old mouse brain nuclei was larger in size and relatively unaffected by the presence of cytosol. Although cytosol caused an increase in the amounts of poly[A]-RNA in nuclei of 2-day-old and adult animals, no comparable effect could be measured in nuclei from 10-day-old brain tissue.", "contents": "The influence of brain cytosol on RNA synthesis and RNA products of isolated mouse brain nuclei. The incubation of isolated nuclei obtained from 10-day-old mouse brain in the presence of brain cell cytosol resulted in an increase in the synthesis of RNA. Under conditions of saturating concentrations of nucleoside triphosphates, the influence of cytosol could not be duplicated by the addition of cyclic nucleotides. The stimulatory activity of cytosol on brain nuclear RNA synthesis could not be attributed to either alterations in the permeability of the nuclear envelope or an increased uptake of radioactively-labeled precursors. Sucrose gradient analysis demonstrated that the RNA products synthesized by nuclei isolated from 10-day-old and adult mouse brain were of a relatively low molecular weight. However, the addition of cytosol resulted in a significant increase in the size of the RNA transcripts. In contrast to the observations with 10-day-old and adult brain nuclei, the RNA from 2-day-old mouse brain nuclei was larger in size and relatively unaffected by the presence of cytosol. Although cytosol caused an increase in the amounts of poly[A]-RNA in nuclei of 2-day-old and adult animals, no comparable effect could be measured in nuclei from 10-day-old brain tissue."}
{"id": "PMID:218127", "title": "Met-enkephalin: rapid separation from brain extracts using high-pressure liquid chromatography, and quantitation by binding assay.", "content": "Met-enkephalin can be rapidly separated with high recovery from leu-enkephalin, beta-endorphin, and enkephalin metabolites by high-pressure liquid chromatography on a Dupont SCX column. The technique permits separation of endogenous enkephalins from brain extracts for measurement by opiate-receptor binding assay, immunoassay, or for study of the incorporation of radiolabeled amino acids into enkephalin. Using this technique, met-enkephalin was separated from striatal extracts of rats killed by focused microwave irradiation and quantitated by the opiate-receptor binding assay. The concentration of met-enkephalin in the column eluate was 1.3 micron/g tissue. This value is comparable to that obtained by radioimmunoassay without purification of the extracts.", "contents": "Met-enkephalin: rapid separation from brain extracts using high-pressure liquid chromatography, and quantitation by binding assay. Met-enkephalin can be rapidly separated with high recovery from leu-enkephalin, beta-endorphin, and enkephalin metabolites by high-pressure liquid chromatography on a Dupont SCX column. The technique permits separation of endogenous enkephalins from brain extracts for measurement by opiate-receptor binding assay, immunoassay, or for study of the incorporation of radiolabeled amino acids into enkephalin. Using this technique, met-enkephalin was separated from striatal extracts of rats killed by focused microwave irradiation and quantitated by the opiate-receptor binding assay. The concentration of met-enkephalin in the column eluate was 1.3 micron/g tissue. This value is comparable to that obtained by radioimmunoassay without purification of the extracts."}
{"id": "PMID:218128", "title": "ACTH-induced inhibition of endogenous rat brain protein phosphorylation in vitro: structure activity.", "content": "ACTH1--24 inhibits the endogenous phosphorylation in vitro of distinct SPM protein bands. Using N-terminal fragments of ACTH, the structure-activity requirements for this effect were studied. A rather complex interaction of the ACTH fragments with endogenous SPM phosphorylation was observed. The effects were not only dependent on the primary structure of the peptide used, but also on the protein band studied and the ATP/SPM ratio used in the incubation system. ACTH1--24 did not interfere with the ATP-hydrolyzing activity of the SPM preparation, nor did it influence the endogenous phosphatase activity. Therefore, a direct interaction of ACTH with SPM protein kinase(s) is likely to be responsible for its effect on phosphorylation.", "contents": "ACTH-induced inhibition of endogenous rat brain protein phosphorylation in vitro: structure activity. ACTH1--24 inhibits the endogenous phosphorylation in vitro of distinct SPM protein bands. Using N-terminal fragments of ACTH, the structure-activity requirements for this effect were studied. A rather complex interaction of the ACTH fragments with endogenous SPM phosphorylation was observed. The effects were not only dependent on the primary structure of the peptide used, but also on the protein band studied and the ATP/SPM ratio used in the incubation system. ACTH1--24 did not interfere with the ATP-hydrolyzing activity of the SPM preparation, nor did it influence the endogenous phosphatase activity. Therefore, a direct interaction of ACTH with SPM protein kinase(s) is likely to be responsible for its effect on phosphorylation."}
{"id": "PMID:218133", "title": "Relationship between ACTH secretion and corticoid binding to specific receptors in perifused adenohypophyses.", "content": "This study reports on the kinetics of glucocorticoid-induced inhibition of ACTH release, together with steroid binding to specific pituitary receptors. It was shown that corticosterone (CORT) inhibited ACTH output provoked by either corticotropin-releasing factor (CRF) extracts or dbcAMP, in a manner which was both dose- and time-dependent. A close correlation appeared to exist between the degree of ACTH blockade and the percentage of filled steroid-binding sites. However, exposure of hypophyses to CORT for a critical period of time was a prerequisite for such a relationship to develop. Furthermore, it was found that dexamethasone (DEX) was more potent than CORT in inhibiting ACTH secretion and, in addition, bound to a greater extent to nuclei of pituitary cells. These data suggest the existence of a close correlation between occupancy of pituitary glucocorticoid receptors and modulation of ACTH secretion.", "contents": "Relationship between ACTH secretion and corticoid binding to specific receptors in perifused adenohypophyses. This study reports on the kinetics of glucocorticoid-induced inhibition of ACTH release, together with steroid binding to specific pituitary receptors. It was shown that corticosterone (CORT) inhibited ACTH output provoked by either corticotropin-releasing factor (CRF) extracts or dbcAMP, in a manner which was both dose- and time-dependent. A close correlation appeared to exist between the degree of ACTH blockade and the percentage of filled steroid-binding sites. However, exposure of hypophyses to CORT for a critical period of time was a prerequisite for such a relationship to develop. Furthermore, it was found that dexamethasone (DEX) was more potent than CORT in inhibiting ACTH secretion and, in addition, bound to a greater extent to nuclei of pituitary cells. These data suggest the existence of a close correlation between occupancy of pituitary glucocorticoid receptors and modulation of ACTH secretion."}
{"id": "PMID:218130", "title": "[Results of polygraphic nocturnal sleep recording in patients with supratentorial brain tumors prior to and following surgery].", "content": "The purpose of the study was to establish the influence exerted by a supratentorial brain tumour on the EEG correlates of sleep, and to compare the results before and after operation. Five patients were studied (aged 38 to 59 years) who were treated surgically for supratentorial expanding lesions: two cases of meningioma (in left parietal area), two cases of glioma (right parietal area and occipital area) and one case of intracerebral haematoma. The control group comprised 5 patients operated upon for lesions of the peripheral nerves of extremities. In the patients with supratentorial brain tumours and after their removal the following sleep parameters were unchanged: total sleep duration, number of awakening during sleep, latency time of the first REM phase and stage 3 NREM (deep and superficial sleep). The amount of REM sleep increased after tumour removal. REM-sleep density was selectively and permanently disturbed. In presence of tumour REM-sleep density was found in traces only, after tumour removal it increased but showed a permanent high-grade deficit in relation to controls.", "contents": "[Results of polygraphic nocturnal sleep recording in patients with supratentorial brain tumors prior to and following surgery]. The purpose of the study was to establish the influence exerted by a supratentorial brain tumour on the EEG correlates of sleep, and to compare the results before and after operation. Five patients were studied (aged 38 to 59 years) who were treated surgically for supratentorial expanding lesions: two cases of meningioma (in left parietal area), two cases of glioma (right parietal area and occipital area) and one case of intracerebral haematoma. The control group comprised 5 patients operated upon for lesions of the peripheral nerves of extremities. In the patients with supratentorial brain tumours and after their removal the following sleep parameters were unchanged: total sleep duration, number of awakening during sleep, latency time of the first REM phase and stage 3 NREM (deep and superficial sleep). The amount of REM sleep increased after tumour removal. REM-sleep density was selectively and permanently disturbed. In presence of tumour REM-sleep density was found in traces only, after tumour removal it increased but showed a permanent high-grade deficit in relation to controls."}
{"id": "PMID:218131", "title": "Studies of cultured human and simian fetal brain cells. II. Infections with human (BK) and simian (SV40) papovaviruses.", "content": "Both simian virus 40 (SV40) and BK viruses infected and lysed not only oligodendroblasts and astrocytes, but also neuroblasts and epithelioid or mesenchymal cells in cultures of fetal brain cells derived from human, rhesus, and cynomolgus hosts. Lytic infections of these four cell types differed ultrastructurally in the amount and arrangement of virions in the nucleus, the extent of nuclear membrane redundancy, the presence of nuclear virion arrays, and the amounts of virions in the cytoplasm. However, major differences were not noted between SV40 and BK viruses, nor between different species of origin or region of brain explanted. Modified astrocytic cells persisted in cultures from all three sources after infection by either virus. These cells stained for glial fibrillary acidic protein (GFAP) and polyomavirus tumour (T) antigen, but did not subculture indefinitely.", "contents": "Studies of cultured human and simian fetal brain cells. II. Infections with human (BK) and simian (SV40) papovaviruses. Both simian virus 40 (SV40) and BK viruses infected and lysed not only oligodendroblasts and astrocytes, but also neuroblasts and epithelioid or mesenchymal cells in cultures of fetal brain cells derived from human, rhesus, and cynomolgus hosts. Lytic infections of these four cell types differed ultrastructurally in the amount and arrangement of virions in the nucleus, the extent of nuclear membrane redundancy, the presence of nuclear virion arrays, and the amounts of virions in the cytoplasm. However, major differences were not noted between SV40 and BK viruses, nor between different species of origin or region of brain explanted. Modified astrocytic cells persisted in cultures from all three sources after infection by either virus. These cells stained for glial fibrillary acidic protein (GFAP) and polyomavirus tumour (T) antigen, but did not subculture indefinitely."}
{"id": "PMID:218136", "title": "The accuracy of predicting histologic grades of supratentorial astrocytomas on the basis of computerized tomography and cerebral angiography.", "content": "This report concerns a group of 49 patients who had been diagnosed as having gliomas on the basis of CT scans plus angiograms and for whom histologic proof was available. Ninety percent were found to be gliomas, 4% were metastases, and histology was unclear in the rest. Combining the CT criteria of inhomogeneous enhancement and surrounding edema with one or more of three angiographic signs (early venous drainage, stain, abnormal vessels) allowed a more confident diagnosis of glioblastoma.", "contents": "The accuracy of predicting histologic grades of supratentorial astrocytomas on the basis of computerized tomography and cerebral angiography. This report concerns a group of 49 patients who had been diagnosed as having gliomas on the basis of CT scans plus angiograms and for whom histologic proof was available. Ninety percent were found to be gliomas, 4% were metastases, and histology was unclear in the rest. Combining the CT criteria of inhomogeneous enhancement and surrounding edema with one or more of three angiographic signs (early venous drainage, stain, abnormal vessels) allowed a more confident diagnosis of glioblastoma."}
{"id": "PMID:218132", "title": "Progression of herpes encephalitis in rabbits following the intra-ocular injection of type I virus.", "content": "The injection of HSV type I into the vitreous body of the eye in the 18-day-old albino rabbits consistently induces herpes encephalitis with 90% survival. The longterm observations up to 64 days post-inculation indicate that HSV travels slowly by cell-to-cell infection of neuroglia. The lesions follow a defined anatomical pathway producing a progressive disease not dissimilar to the natural human disease. Semiserial (1 micron) sections show that as the infection progresses tissue repair follows. It appears that HSV does not become latent, repeated episodes of viral activity cause further damage with which the repair does not keep pace. By the sixteenth day virus particles and lesions are found in contralateral side of the chiasma, lateral geniculate body and both optic nerves, but not in the ipsilateral geniculate body. This suggests that the virus does not follow the axonal route.", "contents": "Progression of herpes encephalitis in rabbits following the intra-ocular injection of type I virus. The injection of HSV type I into the vitreous body of the eye in the 18-day-old albino rabbits consistently induces herpes encephalitis with 90% survival. The longterm observations up to 64 days post-inculation indicate that HSV travels slowly by cell-to-cell infection of neuroglia. The lesions follow a defined anatomical pathway producing a progressive disease not dissimilar to the natural human disease. Semiserial (1 micron) sections show that as the infection progresses tissue repair follows. It appears that HSV does not become latent, repeated episodes of viral activity cause further damage with which the repair does not keep pace. By the sixteenth day virus particles and lesions are found in contralateral side of the chiasma, lateral geniculate body and both optic nerves, but not in the ipsilateral geniculate body. This suggests that the virus does not follow the axonal route."}
{"id": "PMID:218137", "title": "[Embolization and balloon occlusions in tumoral processes: seven years' experience (author's transl)].", "content": "The authors report 169 therapeutic embolizations in cases of tumoral lesions in the craniocerebral, ENT, and vertebrospinal territories. Most endovascular occlusions performed for tumoral processes are presurgical indications, with the aim of reducing hemorrhage at operation. Embolization becomes practically mandatory for nasopharyngeal angiofibromas, considerably reducing the peroperative bleeding. Indications of embolization for meningiomas must be discussed according to the size and location of the tumors: embolization is especially useful in large tumors or those inserted on the base of the skull, mainly in the middle fossa. In chemodectomas, embolization can be used presurgically or on its own when surgery becomes impossible; angiographic follow-up shows that secondary repermeabilization is frequent in spite of clinical improvement. In malignant tumors of the craniofacial region, indications of embolization must be considered with care because failure of vascularization tends to make radiotherapy less efficient; in these cases, embolization can be useful in reducing pain or to contend with cataclysmal hemorrhages.", "contents": "[Embolization and balloon occlusions in tumoral processes: seven years' experience (author's transl)]. The authors report 169 therapeutic embolizations in cases of tumoral lesions in the craniocerebral, ENT, and vertebrospinal territories. Most endovascular occlusions performed for tumoral processes are presurgical indications, with the aim of reducing hemorrhage at operation. Embolization becomes practically mandatory for nasopharyngeal angiofibromas, considerably reducing the peroperative bleeding. Indications of embolization for meningiomas must be discussed according to the size and location of the tumors: embolization is especially useful in large tumors or those inserted on the base of the skull, mainly in the middle fossa. In chemodectomas, embolization can be used presurgically or on its own when surgery becomes impossible; angiographic follow-up shows that secondary repermeabilization is frequent in spite of clinical improvement. In malignant tumors of the craniofacial region, indications of embolization must be considered with care because failure of vascularization tends to make radiotherapy less efficient; in these cases, embolization can be useful in reducing pain or to contend with cataclysmal hemorrhages."}
{"id": "PMID:218139", "title": "Embolization and surgical removal of nasopharyngeal angiofibroma.", "content": "The usefulness of embolization of one or several feeding arteries before surgical removal of nasopharyngeal angiofibroma has been proven. However, there are two questions which remain: (a) At what point should the embolization stop? (B) What is the optimal delay between embolization and operation? These questions are discussed but not resolved.", "contents": "Embolization and surgical removal of nasopharyngeal angiofibroma. The usefulness of embolization of one or several feeding arteries before surgical removal of nasopharyngeal angiofibroma has been proven. However, there are two questions which remain: (a) At what point should the embolization stop? (B) What is the optimal delay between embolization and operation? These questions are discussed but not resolved."}
{"id": "PMID:218140", "title": "[Comparison of CT, scintigraphy, and angiography in the topographic and pathological diagnosis of 300 supratentorial tumors (author's transl)].", "content": "The results of CT, scintigraphy (CSS), and angiography in 300 supratentorial cerebral tumors were compared with regard to the topographic and pathological diagnosis proposed in the initial reports. CT elucidated the topography in 98% of the cases and the pathology in variable percentages, depending on the type of tumor. The use of scintigraphy provided a high accuracy of pathological diagnosis. Except for meningiomas, arteriography was less accurate than the two other methods of examination. A radiological management of supratentorial cerebral tumors is proposed based on clinical and CT data.", "contents": "[Comparison of CT, scintigraphy, and angiography in the topographic and pathological diagnosis of 300 supratentorial tumors (author's transl)]. The results of CT, scintigraphy (CSS), and angiography in 300 supratentorial cerebral tumors were compared with regard to the topographic and pathological diagnosis proposed in the initial reports. CT elucidated the topography in 98% of the cases and the pathology in variable percentages, depending on the type of tumor. The use of scintigraphy provided a high accuracy of pathological diagnosis. Except for meningiomas, arteriography was less accurate than the two other methods of examination. A radiological management of supratentorial cerebral tumors is proposed based on clinical and CT data."}
{"id": "PMID:218141", "title": "Impact of CT in the neurosurgical management of intracranial tumors.", "content": "A total of 103 brain tumor patients examined with CT, radionuclide brain scan, and angiography or pneumoencephalography, and all surgically verified, were studied to evaluate the impact of CT on the neurosurgical handling of brain tumors. CT alone was usually sufficient for optimal handling of astrocytoma patients, angiography in most meningioma cases, and pneumoencephalography in cases with sellar, suprasellar, and some other midline tumors. Information obtained only through CT sometimes altered the therapy. Sometimes it led to biopsy instead of a meaningless attempt at a 'radical' excision: in other cases it permitted a 'radical' excision otherwise not possible.", "contents": "Impact of CT in the neurosurgical management of intracranial tumors. A total of 103 brain tumor patients examined with CT, radionuclide brain scan, and angiography or pneumoencephalography, and all surgically verified, were studied to evaluate the impact of CT on the neurosurgical handling of brain tumors. CT alone was usually sufficient for optimal handling of astrocytoma patients, angiography in most meningioma cases, and pneumoencephalography in cases with sellar, suprasellar, and some other midline tumors. Information obtained only through CT sometimes altered the therapy. Sometimes it led to biopsy instead of a meaningless attempt at a 'radical' excision: in other cases it permitted a 'radical' excision otherwise not possible."}
{"id": "PMID:218143", "title": "Parainfluenza 1 (6/94) virus-induced white matter degeneration: enhancement by adoptive transfer of virus-sensitized immunocytes.", "content": "Intracerebral (i.c.) inoculation of parainfluenza 1 (6/94) virus into weanling Lewis rats produced meningitis, choroiditis, ependymitis, and a rare noninflammatory white matter degeneration (WMD). Adoptive transfer of immune spleen cells (ISC), 3 to 5 days after virus infection, significantly increased the incidence of WMD. Conversely ISC given 2 days prior to virus infection not only protected rats from developing WMD, but also from developing meningitis, choroiditis, or ependymitis. Thus the temporal relationship of 6/94 virus inoculation to the virus-specific immune response appears critical in determining whether WMD will develop in association with 6/94 virus infection. Although sensitized immunocytes may prevent pathologic changes if given prior to virus inoculation, such immunocytes enhance the production of WMD if given after such inoculation. These studies underline the dual role of the immune response in 6/94 virus infection, and indicate that 6/94 virus-induced WMD is, in part, immunemediated.", "contents": "Parainfluenza 1 (6/94) virus-induced white matter degeneration: enhancement by adoptive transfer of virus-sensitized immunocytes. Intracerebral (i.c.) inoculation of parainfluenza 1 (6/94) virus into weanling Lewis rats produced meningitis, choroiditis, ependymitis, and a rare noninflammatory white matter degeneration (WMD). Adoptive transfer of immune spleen cells (ISC), 3 to 5 days after virus infection, significantly increased the incidence of WMD. Conversely ISC given 2 days prior to virus infection not only protected rats from developing WMD, but also from developing meningitis, choroiditis, or ependymitis. Thus the temporal relationship of 6/94 virus inoculation to the virus-specific immune response appears critical in determining whether WMD will develop in association with 6/94 virus infection. Although sensitized immunocytes may prevent pathologic changes if given prior to virus inoculation, such immunocytes enhance the production of WMD if given after such inoculation. These studies underline the dual role of the immune response in 6/94 virus infection, and indicate that 6/94 virus-induced WMD is, in part, immunemediated."}
{"id": "PMID:218144", "title": "Subacute sclerosing panencephalitis with unusual ocular movements: polygraphic studies.", "content": "A 5-year-old child with subacute sclerosing panencephalitis had continuous involuntary ocular movements while awake. At this stage of illness, stereotyped periodic EEG complexes over the two hemispheres were asynchronous. Polygraphic studies showed three diffrent types of ocular movements, each apparently related to the degree of phase shift between the EEG complexes from the two hemispheres. The involuntary ocular movements in one direction were always preceded by periodic EEG complexes from the contralateral hemisphere. Overnight polygraphic studies revealed early disruption of non-rapid eye movement (NREM) sleep patterns and preservation of rapid eye movement (REM) sleep, even in a late stage of illness.", "contents": "Subacute sclerosing panencephalitis with unusual ocular movements: polygraphic studies. A 5-year-old child with subacute sclerosing panencephalitis had continuous involuntary ocular movements while awake. At this stage of illness, stereotyped periodic EEG complexes over the two hemispheres were asynchronous. Polygraphic studies showed three diffrent types of ocular movements, each apparently related to the degree of phase shift between the EEG complexes from the two hemispheres. The involuntary ocular movements in one direction were always preceded by periodic EEG complexes from the contralateral hemisphere. Overnight polygraphic studies revealed early disruption of non-rapid eye movement (NREM) sleep patterns and preservation of rapid eye movement (REM) sleep, even in a late stage of illness."}
{"id": "PMID:218145", "title": "Narcolepsy: regional cerebral blood flow during sleep and wakefulness.", "content": "Serial measurements of regional cerebral blood flow were made by the 135Xe inhalation method during the early stages of sleep and wakefulness in eight normal volunteers and 12 patients with narcolepsy. Electroencephalogram, electro-oculogram, and submental electromyogram were recorded simultaneously. In normals, mean hemispheric gray matter blood flow (Fg) during stages I and II sleep was significantly less (-9.2 percent) than waking values (84.3 +/- 13 ml per 100 gm brain per minute). Maximum regional blood flow decreases during sleep occurred in the brainstem-cerebellar (-25.1 percent), right inferior temporal (-23.1 percent) and bilateral frontal (-18.9 percent) regions (p less than 0.05). In patients with narcolepsy, mean hemispheric Fg while awake was 80.5 +/- 13 ml per 100 gm brain per minute. During REM sleep (n = 2), mean hemispheric Fg increased by 9.8 percent concurrently with large increases (+34.6 percent) in brainstem-cerebellar region flow. During stages I and II sleep without REM (n = 6), there were significant increases in mean hemispheric Fg of +/-20.2 percent (p less than 0.01) and brainstem-cerebellar Fg of 38.0 percent (p less than 0.01), just the opposite of changes in normals. In narcolepsy, there appears to be a reversal of normal cerebral deactivation patterns, particularly involving the brainstem, during stages I and II sleep.", "contents": "Narcolepsy: regional cerebral blood flow during sleep and wakefulness. Serial measurements of regional cerebral blood flow were made by the 135Xe inhalation method during the early stages of sleep and wakefulness in eight normal volunteers and 12 patients with narcolepsy. Electroencephalogram, electro-oculogram, and submental electromyogram were recorded simultaneously. In normals, mean hemispheric gray matter blood flow (Fg) during stages I and II sleep was significantly less (-9.2 percent) than waking values (84.3 +/- 13 ml per 100 gm brain per minute). Maximum regional blood flow decreases during sleep occurred in the brainstem-cerebellar (-25.1 percent), right inferior temporal (-23.1 percent) and bilateral frontal (-18.9 percent) regions (p less than 0.05). In patients with narcolepsy, mean hemispheric Fg while awake was 80.5 +/- 13 ml per 100 gm brain per minute. During REM sleep (n = 2), mean hemispheric Fg increased by 9.8 percent concurrently with large increases (+34.6 percent) in brainstem-cerebellar region flow. During stages I and II sleep without REM (n = 6), there were significant increases in mean hemispheric Fg of +/-20.2 percent (p less than 0.01) and brainstem-cerebellar Fg of 38.0 percent (p less than 0.01), just the opposite of changes in normals. In narcolepsy, there appears to be a reversal of normal cerebral deactivation patterns, particularly involving the brainstem, during stages I and II sleep."}
{"id": "PMID:218146", "title": "Single-fiber electromyography in myasthenia gravis.", "content": "One-hundred-sixty single-fiber EMG studies of the extensor digitorum communis muscle were performed on 127 patients with myasthenia gravis; 131 demonstrated defective neuromuscular transmission. Jitter determinations in the biceps, deltoid or frontalis muscles increased the diagnostic yield significantly. Evoked-potential EMG studies were abnormal in less than 50 percent of patients in whom they were performed. The most sensitive criterion of abnormality was the percentage of fibers with increased jitter; the sensitivity of the test was enhanced, however, if the mean jitter of the tested muscle was also used as a criterion of abnormality. Since increased jitter may also be seen in primary muscle and nerve disease, these disorders must be excluded by other means before diagnosing myasthenia gravis on the basis of the single-fiber studies.", "contents": "Single-fiber electromyography in myasthenia gravis. One-hundred-sixty single-fiber EMG studies of the extensor digitorum communis muscle were performed on 127 patients with myasthenia gravis; 131 demonstrated defective neuromuscular transmission. Jitter determinations in the biceps, deltoid or frontalis muscles increased the diagnostic yield significantly. Evoked-potential EMG studies were abnormal in less than 50 percent of patients in whom they were performed. The most sensitive criterion of abnormality was the percentage of fibers with increased jitter; the sensitivity of the test was enhanced, however, if the mean jitter of the tested muscle was also used as a criterion of abnormality. Since increased jitter may also be seen in primary muscle and nerve disease, these disorders must be excluded by other means before diagnosing myasthenia gravis on the basis of the single-fiber studies."}
{"id": "PMID:218147", "title": "Metachromatic leukodystrophy: a comparative study of the ultrastructural findings in the peripheral nervous system of three cases, one of the late infantile, one of the juvenile and one of the adult form of the disease.", "content": "The ultrastructural findings in the peripheral nerve of three cases of M. L. D., namely of the late infantile, the juvenile and the adult form are described. The pathological changes consist of two phenomena: segmental demyelination and lysosomal storage of sulfatides, both probably separate results of a deficiency of the enzyme Arylsulfatase A. Some differences are found in the degree of segmental demyelination and the type of lysosomal storage products. A possible relation between these differences and the supposed difference in the defect of the enzyme Arylsulfatase A, responsible for the different subtypes of the disease, is postulated.", "contents": "Metachromatic leukodystrophy: a comparative study of the ultrastructural findings in the peripheral nervous system of three cases, one of the late infantile, one of the juvenile and one of the adult form of the disease. The ultrastructural findings in the peripheral nerve of three cases of M. L. D., namely of the late infantile, the juvenile and the adult form are described. The pathological changes consist of two phenomena: segmental demyelination and lysosomal storage of sulfatides, both probably separate results of a deficiency of the enzyme Arylsulfatase A. Some differences are found in the degree of segmental demyelination and the type of lysosomal storage products. A possible relation between these differences and the supposed difference in the defect of the enzyme Arylsulfatase A, responsible for the different subtypes of the disease, is postulated."}
{"id": "PMID:218151", "title": "Estrogen replacement therapy I: a 10-year prospective study in the relationship to osteoporosis.", "content": "A 10-year, double-blind prospective study was undertaken to evaluate the effects of estrogen replacement therapy. The sample population consisted of 84 pairs of randomly chosen postmenopausal patients who were matched for age and diagnosis. One half of the patients received conjugated estrogens and cyclic progesterone, while the other half received placebo. Estrogen-treated patients whose therapy started within 3 years of menopause showed improvement or no increase in osteoporosis. Control patients demonstrate an increase in their osteoporosis.", "contents": "Estrogen replacement therapy I: a 10-year prospective study in the relationship to osteoporosis. A 10-year, double-blind prospective study was undertaken to evaluate the effects of estrogen replacement therapy. The sample population consisted of 84 pairs of randomly chosen postmenopausal patients who were matched for age and diagnosis. One half of the patients received conjugated estrogens and cyclic progesterone, while the other half received placebo. Estrogen-treated patients whose therapy started within 3 years of menopause showed improvement or no increase in osteoporosis. Control patients demonstrate an increase in their osteoporosis."}
{"id": "PMID:218152", "title": "Genital herpes simplex virus (HSV) isolation during pregnancy.", "content": "Eight patients with laboratory-confirmed herpes simplex virus (HSV) infection were cultured repeatedly during their pregnancies. Two of the 8 patients did not have typical HSV lesions. All patients became culture negative and all delivered normal infants vaginally. Because asymptomatic women can transmit HSV to neonates at parturition, it is important to do viral cultures as well as to clinically assess the mother.", "contents": "Genital herpes simplex virus (HSV) isolation during pregnancy. Eight patients with laboratory-confirmed herpes simplex virus (HSV) infection were cultured repeatedly during their pregnancies. Two of the 8 patients did not have typical HSV lesions. All patients became culture negative and all delivered normal infants vaginally. Because asymptomatic women can transmit HSV to neonates at parturition, it is important to do viral cultures as well as to clinically assess the mother."}
{"id": "PMID:218153", "title": "In vitro cultivation of human tumor tissues. II. Morphological and virological characterization of three cell lines.", "content": "Nineteen human tumors, mostly of sarcomatous nature, were cultured in vitro. Three cell lines were isolated and further characterized: MG-57 derived from a giant cell tumor, MG-63 derived from an osteosarcoma and MG-72 derived from a xanthohistiocytoma. The cell lines varied in morphology and growth pattern. An abnormal karyotype with marker chromosomes was present in Mg-63 and MG-72. None of the cell lines spontaneously produced detectable C-type virus particles. Stimulation with IUDR and dexamethasone also failed to induce detectable particle release.", "contents": "In vitro cultivation of human tumor tissues. II. Morphological and virological characterization of three cell lines. Nineteen human tumors, mostly of sarcomatous nature, were cultured in vitro. Three cell lines were isolated and further characterized: MG-57 derived from a giant cell tumor, MG-63 derived from an osteosarcoma and MG-72 derived from a xanthohistiocytoma. The cell lines varied in morphology and growth pattern. An abnormal karyotype with marker chromosomes was present in Mg-63 and MG-72. None of the cell lines spontaneously produced detectable C-type virus particles. Stimulation with IUDR and dexamethasone also failed to induce detectable particle release."}
{"id": "PMID:218154", "title": "A clinical trial of topically applied 3 percent vidarabine against recurrent herpes labialis.", "content": "Seventy-six participants were enrolled in a clinical trial to determine therapeutic effectiveness of 3 percent vidarabine applied topically to recurrent perioral herpetic lesions. Following a 6- to- 12-month natural history phase, a 12-month clinical trial was conducted. Seventy participants developed 463 lesions during 361 episodes. Three percent vidarabine in a water-miscible gel was applied six times daily for 7 days to each lesion in the experimental group. Identically packaged placebo was used by the control group. Group assignment was by computer-generated randomization. Lesion size was reduced when vidarabine, rather than placebo, was applied. The difference was statistically significant (Student's t test, P = 0.02). Vesiculation followed tingling more rapidly when vidarabine, rather than placebo, was applied prior to vesiculation (P = 0.05). No significant difference between the two groups was found in episode frequency or lesion duration. Adverse reactions to vidarabine were not experienced.", "contents": "A clinical trial of topically applied 3 percent vidarabine against recurrent herpes labialis. Seventy-six participants were enrolled in a clinical trial to determine therapeutic effectiveness of 3 percent vidarabine applied topically to recurrent perioral herpetic lesions. Following a 6- to- 12-month natural history phase, a 12-month clinical trial was conducted. Seventy participants developed 463 lesions during 361 episodes. Three percent vidarabine in a water-miscible gel was applied six times daily for 7 days to each lesion in the experimental group. Identically packaged placebo was used by the control group. Group assignment was by computer-generated randomization. Lesion size was reduced when vidarabine, rather than placebo, was applied. The difference was statistically significant (Student's t test, P = 0.02). Vesiculation followed tingling more rapidly when vidarabine, rather than placebo, was applied prior to vesiculation (P = 0.05). No significant difference between the two groups was found in episode frequency or lesion duration. Adverse reactions to vidarabine were not experienced."}
{"id": "PMID:218163", "title": "[Renal receptors of parathyroid hormone and calcitonin (author's transl)].", "content": "The two first steps of the renal cellular action of parathyroid hormone and of calcitonin are the hormonal binding onto specific receptors and the stimulation of adenylate cyclase by the hormone-receptor complex producing an increase in the intra-cellular concentration of 3'-5' cyclic adenosine monophosphate (cyclic AMP). Specific glomerular and tubular receptors for parathyroid hormone have been demonstrated using either tritiated parathyroid hormone or an indirect technique with 125 I labelled specific antibodies. Tubular receptors are localized both in the proximal and distal segments of the nephron. Parathyroid hormone stimulates glomerular and tubular adenylate cyclase. The main unsolved problem is the difficulty for demonstrating high affinity binding sites and stimulation of adenylate cyclase at low physiological concentrations of parathyroid hormone. In man, administration of parathyroid hormone produces a marked increase in the urinary excretion of cyclic AMP chiefly concerning its nephrogenous fraction. The peak of excretion is early and precedes the decrease in phosphate tubular reabsorption. Tubular receptors for calcitonin have been demonstrated using 125 I labelled salmon calcitonin. Calcitonin stimulates renal adenylate cyclase in only some segments of the nephron allowing receptors for calcitonin to be localized in the wide ascending branch of Henle's loop and the initial part of the convoluted distal tubule. In the presence of guanylnucleotides, binding of calcitonin onto its receptors and activation of adenylate cyclase are observed in the range of physiological concentrations of calcitonin in the rat. In man, administration of calcitonin produces a moderate increase in the urinary excretion of cyclic AMP coming from a non renal tissue.", "contents": "[Renal receptors of parathyroid hormone and calcitonin (author's transl)]. The two first steps of the renal cellular action of parathyroid hormone and of calcitonin are the hormonal binding onto specific receptors and the stimulation of adenylate cyclase by the hormone-receptor complex producing an increase in the intra-cellular concentration of 3'-5' cyclic adenosine monophosphate (cyclic AMP). Specific glomerular and tubular receptors for parathyroid hormone have been demonstrated using either tritiated parathyroid hormone or an indirect technique with 125 I labelled specific antibodies. Tubular receptors are localized both in the proximal and distal segments of the nephron. Parathyroid hormone stimulates glomerular and tubular adenylate cyclase. The main unsolved problem is the difficulty for demonstrating high affinity binding sites and stimulation of adenylate cyclase at low physiological concentrations of parathyroid hormone. In man, administration of parathyroid hormone produces a marked increase in the urinary excretion of cyclic AMP chiefly concerning its nephrogenous fraction. The peak of excretion is early and precedes the decrease in phosphate tubular reabsorption. Tubular receptors for calcitonin have been demonstrated using 125 I labelled salmon calcitonin. Calcitonin stimulates renal adenylate cyclase in only some segments of the nephron allowing receptors for calcitonin to be localized in the wide ascending branch of Henle's loop and the initial part of the convoluted distal tubule. In the presence of guanylnucleotides, binding of calcitonin onto its receptors and activation of adenylate cyclase are observed in the range of physiological concentrations of calcitonin in the rat. In man, administration of calcitonin produces a moderate increase in the urinary excretion of cyclic AMP coming from a non renal tissue."}
{"id": "PMID:218167", "title": "Polyoma infected cells contain at least three spliced late RNAs.", "content": "Poly(A)-containing polyoma cytoplasmic RNA was hybridized with linear double-stranded polyoma DNA and RNA displacement loops (R-loops) were formed. The structures visualized in the electron microscope are consistent with the conclusion that there are at least three late polyoma specific RNAs and that the leader sequences at the 5' ends of these viral RNAs are not coded immediately adjacent to the bodies of the RNAs. Measurements carried out on the R-loop structures have provided the locations on the physical map of polyoma DNA, for the bodies and leaders of the RNAs and the length of the bodies, leaders and the corresponding intervening DNA sequences.", "contents": "Polyoma infected cells contain at least three spliced late RNAs. Poly(A)-containing polyoma cytoplasmic RNA was hybridized with linear double-stranded polyoma DNA and RNA displacement loops (R-loops) were formed. The structures visualized in the electron microscope are consistent with the conclusion that there are at least three late polyoma specific RNAs and that the leader sequences at the 5' ends of these viral RNAs are not coded immediately adjacent to the bodies of the RNAs. Measurements carried out on the R-loop structures have provided the locations on the physical map of polyoma DNA, for the bodies and leaders of the RNAs and the length of the bodies, leaders and the corresponding intervening DNA sequences."}
{"id": "PMID:218168", "title": "An electron microscope study of the proteins attached to polio virus RNA and its replicative form (RF).", "content": "A recently described method (Wu, M. and Davidson, N. (1978), Nucleic Acids Research 5, in press) for visualizing proteins attached to nucleic acids in the electron microscope has been applied to study proteins attached to poliovirion RNA and to the viral double-stranded intracellular RF form. A protein is found at the 5' end of the plus strand virion RNA, and protein components are found at both ends of the duplex RF. In the RF as usually extracted, there is frequently a larger or compound protein aggregate at the end which contains the 3' end of the plus strand and the 5' end of the minus strand. Banding in CsCl-guanidinium hydrochloride in the presence of sarkosyl causes dissociation of some components of this aggregate, leaving both ends labeled with the covalently bound VPg. These results confirm and extend previous biochemical studies of proteins bound to poliovirion RNA and to the RF form.", "contents": "An electron microscope study of the proteins attached to polio virus RNA and its replicative form (RF). A recently described method (Wu, M. and Davidson, N. (1978), Nucleic Acids Research 5, in press) for visualizing proteins attached to nucleic acids in the electron microscope has been applied to study proteins attached to poliovirion RNA and to the viral double-stranded intracellular RF form. A protein is found at the 5' end of the plus strand virion RNA, and protein components are found at both ends of the duplex RF. In the RF as usually extracted, there is frequently a larger or compound protein aggregate at the end which contains the 3' end of the plus strand and the 5' end of the minus strand. Banding in CsCl-guanidinium hydrochloride in the presence of sarkosyl causes dissociation of some components of this aggregate, leaving both ends labeled with the covalently bound VPg. These results confirm and extend previous biochemical studies of proteins bound to poliovirion RNA and to the RF form."}
{"id": "PMID:218169", "title": "Selection of methionine tRNAs by avian oncornaviruses.", "content": "The free 4S RNA of avian RNA tumor viruses is greatly enriched in one of the four methionine tRNAs of the host cells, tRNA4Met. On the assumption that viral tRNAMet forms are identical to the corresponding tRNAs of mouse or chick cells, the following conclusions were drawn concerning the tRNAMet content of oncornaviruses: (1) tRNAMet species may be compartmentalised within the host cells, and the viral tRNA pool could reflect the cellular compartment in which viral maturation takes place since tRNAMet forms distribute unevenly between different fractions of a cell homogenate. (2) tRNA4Met appears to have no special role in the modulation of protein synthesis in as much as no functional difference between tRNA2Met and tRNA3Met, tRNA4Met could be demonstrated in in vitro protein synthesising systems. (3) tRNA4Met differs in nucleotide sequence from all other host cell tRNAMet forms except possibly tRNA2Met. The nucleotide sequences of two tRNAMet species, tRNA1Met and tRNA4Met, have already been determined and the sequence of another host cell tRNAMet, tRNA3Met, was derived from the analogy of its sequence to that of tRNA4Met since the two molecules differ in only 6 nucleotides out of 76. (4) Avian myeloblastosis virus reverse transcriptase has been shown to bind specifically tRNA4Met and tRNATrp in whole cell tRNA and therefore the free tRNA4Met in the virion particle may exist substantially bound to virion-associated transcriptase.", "contents": "Selection of methionine tRNAs by avian oncornaviruses. The free 4S RNA of avian RNA tumor viruses is greatly enriched in one of the four methionine tRNAs of the host cells, tRNA4Met. On the assumption that viral tRNAMet forms are identical to the corresponding tRNAs of mouse or chick cells, the following conclusions were drawn concerning the tRNAMet content of oncornaviruses: (1) tRNAMet species may be compartmentalised within the host cells, and the viral tRNA pool could reflect the cellular compartment in which viral maturation takes place since tRNAMet forms distribute unevenly between different fractions of a cell homogenate. (2) tRNA4Met appears to have no special role in the modulation of protein synthesis in as much as no functional difference between tRNA2Met and tRNA3Met, tRNA4Met could be demonstrated in in vitro protein synthesising systems. (3) tRNA4Met differs in nucleotide sequence from all other host cell tRNAMet forms except possibly tRNA2Met. The nucleotide sequences of two tRNAMet species, tRNA1Met and tRNA4Met, have already been determined and the sequence of another host cell tRNAMet, tRNA3Met, was derived from the analogy of its sequence to that of tRNA4Met since the two molecules differ in only 6 nucleotides out of 76. (4) Avian myeloblastosis virus reverse transcriptase has been shown to bind specifically tRNA4Met and tRNATrp in whole cell tRNA and therefore the free tRNA4Met in the virion particle may exist substantially bound to virion-associated transcriptase."}
{"id": "PMID:218170", "title": "Quantitative analysis of specific labelled RNA'S using DNA covalently linked to diazobenzyloxymethyl-paper.", "content": "Substantial amounts of DNA (at least 25 microgram per cm2) can be stably bound to diazobenzyloxymethyl (DBM)-paper. Complementary RNA will hybridize to the DNA paper almost completely in 24 hours. Using several different conditions of hybridization and washing, the background of RNA bound non-specifically is very low (between 0.01 and 0.02%) and the efficiency of hybridization is very high (75 to 50% of complementary RNA is bound and retained through the washing procedure). Because the DNA is bound to the paper convalently, it is retained through all the washing and elution steps, and the DNA papers can be re-used many times.", "contents": "Quantitative analysis of specific labelled RNA'S using DNA covalently linked to diazobenzyloxymethyl-paper. Substantial amounts of DNA (at least 25 microgram per cm2) can be stably bound to diazobenzyloxymethyl (DBM)-paper. Complementary RNA will hybridize to the DNA paper almost completely in 24 hours. Using several different conditions of hybridization and washing, the background of RNA bound non-specifically is very low (between 0.01 and 0.02%) and the efficiency of hybridization is very high (75 to 50% of complementary RNA is bound and retained through the washing procedure). Because the DNA is bound to the paper convalently, it is retained through all the washing and elution steps, and the DNA papers can be re-used many times."}
{"id": "PMID:218171", "title": "A method for the enzymatic synthesis and purification of [alpha-32P] nucleoside triphosphates.", "content": "A simplified method is described for the enzymatic synthesis and purification of [alpha-32P]ribo- and deoxyribonucleoside triphosphates. The products are obtained at greater than 97% radiochemical purity with yields of 50--70% (relative to 32Pi) by a two-step elution from DEAE-Sephadex. All reactions are done in one vessel as there is no need for intermediate product purifications. This method is therefore suitable for the synthesis of these radioactive compounds on a relatively large scale. The sequential steps of the method involve first the synthesis of [gamma-32P]ATP and the subsequent phosphorylation of nucleoside 3' monophosphate with T4 polynucleotide kinase to yield nucleoside 3', [5'-32P]diphosphate. Hexokinase is used after the T4 reaction to remove any remaining [gamma-32P]ATP. Nucleoside 3',[5'-32P]diphosphate is treated with nuclease P-1 to produce the nucleoside [5'-32P]monophosphate which is phosphorylated to the [alpha-32P]nucleoside triphosphate with pyruvate kinase and nucleoside monophosphate kinase. Adenosine triphosphate used as the phosphate donor for [alpha-32P]deoxynucleoside triphosphate syntheses is readily removed in a second purification step involving affinity chromatography on boronate-polyacrylamide. [alpha-32P]Ribonucleoside triphosphates can be similarly purified when deoxyadenosine triphosphate is used as the phosphate donor.", "contents": "A method for the enzymatic synthesis and purification of [alpha-32P] nucleoside triphosphates. A simplified method is described for the enzymatic synthesis and purification of [alpha-32P]ribo- and deoxyribonucleoside triphosphates. The products are obtained at greater than 97% radiochemical purity with yields of 50--70% (relative to 32Pi) by a two-step elution from DEAE-Sephadex. All reactions are done in one vessel as there is no need for intermediate product purifications. This method is therefore suitable for the synthesis of these radioactive compounds on a relatively large scale. The sequential steps of the method involve first the synthesis of [gamma-32P]ATP and the subsequent phosphorylation of nucleoside 3' monophosphate with T4 polynucleotide kinase to yield nucleoside 3', [5'-32P]diphosphate. Hexokinase is used after the T4 reaction to remove any remaining [gamma-32P]ATP. Nucleoside 3',[5'-32P]diphosphate is treated with nuclease P-1 to produce the nucleoside [5'-32P]monophosphate which is phosphorylated to the [alpha-32P]nucleoside triphosphate with pyruvate kinase and nucleoside monophosphate kinase. Adenosine triphosphate used as the phosphate donor for [alpha-32P]deoxynucleoside triphosphate syntheses is readily removed in a second purification step involving affinity chromatography on boronate-polyacrylamide. [alpha-32P]Ribonucleoside triphosphates can be similarly purified when deoxyadenosine triphosphate is used as the phosphate donor."}
{"id": "PMID:218172", "title": "Characterization of the genomic RNA from a Rous sarcoma virus mutant temperature sensitive for cell transformation.", "content": "We have found that the LA23 t/s mutant of Rous sarcoma virus (phenotype Prague B), even when passaged repeatedly at high multiplicity of infection, does not give rise to transformation defective deletion mutants comparable to those derived from RSV. In view of this fact and of the high rate of production of this mutant at 41 degrees C, we have undertaken a detailed analysis of the genome of this virus by ordering all large T1 oligonucleotides and by determining their nucleotide sequences. The results indicate a high degree of mutation in the onc gene as compared to that of Pr-A or Pr-B.", "contents": "Characterization of the genomic RNA from a Rous sarcoma virus mutant temperature sensitive for cell transformation. We have found that the LA23 t/s mutant of Rous sarcoma virus (phenotype Prague B), even when passaged repeatedly at high multiplicity of infection, does not give rise to transformation defective deletion mutants comparable to those derived from RSV. In view of this fact and of the high rate of production of this mutant at 41 degrees C, we have undertaken a detailed analysis of the genome of this virus by ordering all large T1 oligonucleotides and by determining their nucleotide sequences. The results indicate a high degree of mutation in the onc gene as compared to that of Pr-A or Pr-B."}
{"id": "PMID:218173", "title": "Aminonucleosides and their derivatives. IV. Synthesis of the 3'-amino-3'-deoxynucleoside 5'-phosphates.", "content": "A new procedure has been developed for the synthesis of 3'-amino-3'-deoxyribonucleosides of adenine, cytosine and uracil by condensing the trimethylsilylated bases with peracylated 3-azido-3-deoxyribose derivative. The azido group could subsequently be reduced to amino. The 5'-phosphates of these nucleosides have been prepared and the analogues have been tested for their ability to stimulate the ribosome-catalyzed reaction of 3'(2')-O-(N-formylmethionyl) adenosine 5'-phosphate with phenylalanyl-tRNA.", "contents": "Aminonucleosides and their derivatives. IV. Synthesis of the 3'-amino-3'-deoxynucleoside 5'-phosphates. A new procedure has been developed for the synthesis of 3'-amino-3'-deoxyribonucleosides of adenine, cytosine and uracil by condensing the trimethylsilylated bases with peracylated 3-azido-3-deoxyribose derivative. The azido group could subsequently be reduced to amino. The 5'-phosphates of these nucleosides have been prepared and the analogues have been tested for their ability to stimulate the ribosome-catalyzed reaction of 3'(2')-O-(N-formylmethionyl) adenosine 5'-phosphate with phenylalanyl-tRNA."}
{"id": "PMID:218180", "title": "A combined neurofibroma-granular cell tumor of the middle cranial fossa.", "content": "A case of a combined neurofibroma-granular cell tumor in a 52 years old gunsmith is presented. The tumor developed after an intracranial trigeminal nerve operation 25 years previously. The solid tumor in the left middle cranial fossa had displaced and infiltrated the temporal lobe. It had expanded via the optic nerve into the left orbit, and further the apex partis petrosae was destroyed. The neurofibroma part shows histological aspects of malignancy, the granular cell tumor, considering its infiltrating and destructive growth, may be regarded as malignant as well. In intermingling portions of the tumor, transitional types of fiber-like and granular cells are prominent. In the peripheral zone of the tumor apparently reactively proliferated polynuclear astrocytes are seen with occasionally intracytoplasmatic lymphocytes (emperipolesis?). A short review of the literature and the theories concerning the histogenesis of the granular cell tumor is given. Whereas most authors in recent years suggest a Schwann cell origin, based on electron microscopic findings, this intermediate tumor type motivates us to postulate a mesodermal origin of the granular cell tumor. The question of viral influence is discussed briefly.", "contents": "A combined neurofibroma-granular cell tumor of the middle cranial fossa. A case of a combined neurofibroma-granular cell tumor in a 52 years old gunsmith is presented. The tumor developed after an intracranial trigeminal nerve operation 25 years previously. The solid tumor in the left middle cranial fossa had displaced and infiltrated the temporal lobe. It had expanded via the optic nerve into the left orbit, and further the apex partis petrosae was destroyed. The neurofibroma part shows histological aspects of malignancy, the granular cell tumor, considering its infiltrating and destructive growth, may be regarded as malignant as well. In intermingling portions of the tumor, transitional types of fiber-like and granular cells are prominent. In the peripheral zone of the tumor apparently reactively proliferated polynuclear astrocytes are seen with occasionally intracytoplasmatic lymphocytes (emperipolesis?). A short review of the literature and the theories concerning the histogenesis of the granular cell tumor is given. Whereas most authors in recent years suggest a Schwann cell origin, based on electron microscopic findings, this intermediate tumor type motivates us to postulate a mesodermal origin of the granular cell tumor. The question of viral influence is discussed briefly."}
{"id": "PMID:218186", "title": "[Mechanism of the diuretic action of epiphyseal extracts].", "content": "Experiments on dogs demonstrated that intravenous administration of the epiphysis extracts prevented the antidiuretic action of both the endogenous (traumatic stress) and exogenous (pituitrin) antidiuretic hormone (ADH). Injection of the extract into the renal artery gave a unilateral diuretic effect. The diuretic action of the preparation was eliminated by the block of the alpha-adrenergic receptors, whereas beta-adrenoblockers were ineffective. A conclusion was drawn that the mechanism of the diuretic action of the epiphysis extracts consisted in the competitive suppression of the ADH action at the renal tubules level on account of excitation of the alpha-adrenoceptors and inhibition of the adenylcyclase activity.", "contents": "[Mechanism of the diuretic action of epiphyseal extracts]. Experiments on dogs demonstrated that intravenous administration of the epiphysis extracts prevented the antidiuretic action of both the endogenous (traumatic stress) and exogenous (pituitrin) antidiuretic hormone (ADH). Injection of the extract into the renal artery gave a unilateral diuretic effect. The diuretic action of the preparation was eliminated by the block of the alpha-adrenergic receptors, whereas beta-adrenoblockers were ineffective. A conclusion was drawn that the mechanism of the diuretic action of the epiphysis extracts consisted in the competitive suppression of the ADH action at the renal tubules level on account of excitation of the alpha-adrenoceptors and inhibition of the adenylcyclase activity."}
{"id": "PMID:218187", "title": "[Adrenal cortex and vitamin PP. The effect of corticosteroids on the NAD level in the rat liver after the administration of excess nicotinic acid or nicotinamide].", "content": "The NAD content in the liver was experimentally studied in intact, adrenalectomized rats and those given hydrocortisone following nicotinic acid and nicotinamide administration. The NAD concentration in the liver rose linearly and equally during the first 4 experimental hours after the nicotinamide administration (200 mg/kg). A conclusion was drawn that in administration of exogenous precursors the coenzyme biosynthesis did not depend on the initial hormonal background.", "contents": "[Adrenal cortex and vitamin PP. The effect of corticosteroids on the NAD level in the rat liver after the administration of excess nicotinic acid or nicotinamide]. The NAD content in the liver was experimentally studied in intact, adrenalectomized rats and those given hydrocortisone following nicotinic acid and nicotinamide administration. The NAD concentration in the liver rose linearly and equally during the first 4 experimental hours after the nicotinamide administration (200 mg/kg). A conclusion was drawn that in administration of exogenous precursors the coenzyme biosynthesis did not depend on the initial hormonal background."}
{"id": "PMID:218188", "title": "[Effect of thyroxine on oxidative enzymatic activity in the rat aorta].", "content": "The activity of hexokinase, dehydrogenases of pentose cycle, total lactate dehydrogenase, and cytochrome-C-oxidase level was determined in the aorta of rats with hyperthyroidism caused by the intraperitoneal administration of L-thyroxin. In the administration of hormone doses approaching the physiological ones there was an increase in the activity of cytochrome-C-oxidase and a tendency to the increase of 6-phosphogluconate dehydrogenase. Elevation of the activity of all the enzymes under study, excluding lactate dehydrogenase, and in increase of the amount of extractable protein occurred in the administration of moderate thyroxin doses. An increase of hexokinase and particularly of cytochrome-C-oxidase activity was revealed in hyperthyroidism with phenomena of thyrotoxicosis. The activity of the rest of the enzymes approached control. The data obtained are discussed from the point of view of the role played by thyroid hormones in the pathogenesis of atherosclerosis.", "contents": "[Effect of thyroxine on oxidative enzymatic activity in the rat aorta]. The activity of hexokinase, dehydrogenases of pentose cycle, total lactate dehydrogenase, and cytochrome-C-oxidase level was determined in the aorta of rats with hyperthyroidism caused by the intraperitoneal administration of L-thyroxin. In the administration of hormone doses approaching the physiological ones there was an increase in the activity of cytochrome-C-oxidase and a tendency to the increase of 6-phosphogluconate dehydrogenase. Elevation of the activity of all the enzymes under study, excluding lactate dehydrogenase, and in increase of the amount of extractable protein occurred in the administration of moderate thyroxin doses. An increase of hexokinase and particularly of cytochrome-C-oxidase activity was revealed in hyperthyroidism with phenomena of thyrotoxicosis. The activity of the rest of the enzymes approached control. The data obtained are discussed from the point of view of the role played by thyroid hormones in the pathogenesis of atherosclerosis."}
{"id": "PMID:218191", "title": "Rapid inactivation of cyclooxygenase activity after stimulation of intact platelets.", "content": "Trypsin, thrombin, and ionophore A23187 activate phospholipid breakdown of platelets that have been labeled with [(14)C]arachidonate, releasing their cyclooxygenase and lipoxygenase products. Intact platelets can also very effectively directly degrade low concentrations of exogenous, free [(14)C]arachidonate. Pretreatment of platelets with trypsin, thrombin, or ionophore A23187 for a minimum time of 30 sec leads to complete inactivation of cyclooxygenase activity, as demonstrated by subsequent exposure to [(14)C]arachidonate. Lipoxygenase activity is lost after 5 min. The thrombin-induced inactivation of cyclooxygenase and lipoxygenase is prevented by cyclic AMP (which inhibits the stimulated activity of phospholipase A(2)), although cyclic AMP does not affect the degradation of exogenous [(14)C]arachidonate. Exposure of platelets labeled with [(14)C]arachidonate to unlabeled arachidonate under conditions that lead to use of the latter also results in a similarly rapid inhibition of cyclooxygenase activity, as determined by subsequent challenge with thrombin. Under these conditions lipoxygenase activity is much less markedly inactivated. The arachidonate-induced inhibition of cyclooxygenase activity is not prevented by cyclic AMP. Trypsin does not induce platelet aggregation, and platelets whose cyclooxygenase activity has been inactivated are intact insofar as they are still able to undergo aggregation. These studies demonstrate that operation in intact platelets of the cyclooxygenase pathway, through use of endogenous or exogenous substrate, leads to a very rapid, irreversible inactivation of this enzyme. The lipoxygenase pathway is also progressively impaired, but much less rapidly than the cyclooxygenase enzyme and much less markedly on use of exogenous compared to endogenous substrate. The possible consequences of these physiological processes of spontaneous inactivation are considered.", "contents": "Rapid inactivation of cyclooxygenase activity after stimulation of intact platelets. Trypsin, thrombin, and ionophore A23187 activate phospholipid breakdown of platelets that have been labeled with [(14)C]arachidonate, releasing their cyclooxygenase and lipoxygenase products. Intact platelets can also very effectively directly degrade low concentrations of exogenous, free [(14)C]arachidonate. Pretreatment of platelets with trypsin, thrombin, or ionophore A23187 for a minimum time of 30 sec leads to complete inactivation of cyclooxygenase activity, as demonstrated by subsequent exposure to [(14)C]arachidonate. Lipoxygenase activity is lost after 5 min. The thrombin-induced inactivation of cyclooxygenase and lipoxygenase is prevented by cyclic AMP (which inhibits the stimulated activity of phospholipase A(2)), although cyclic AMP does not affect the degradation of exogenous [(14)C]arachidonate. Exposure of platelets labeled with [(14)C]arachidonate to unlabeled arachidonate under conditions that lead to use of the latter also results in a similarly rapid inhibition of cyclooxygenase activity, as determined by subsequent challenge with thrombin. Under these conditions lipoxygenase activity is much less markedly inactivated. The arachidonate-induced inhibition of cyclooxygenase activity is not prevented by cyclic AMP. Trypsin does not induce platelet aggregation, and platelets whose cyclooxygenase activity has been inactivated are intact insofar as they are still able to undergo aggregation. These studies demonstrate that operation in intact platelets of the cyclooxygenase pathway, through use of endogenous or exogenous substrate, leads to a very rapid, irreversible inactivation of this enzyme. The lipoxygenase pathway is also progressively impaired, but much less rapidly than the cyclooxygenase enzyme and much less markedly on use of exogenous compared to endogenous substrate. The possible consequences of these physiological processes of spontaneous inactivation are considered."}
{"id": "PMID:218192", "title": "DNA binding activity from cultured human fibrolasts that is specific for partially depurinated DNA and that inserts purines into apurinic sites.", "content": "A protein of molecular weight approximately 120,000 was isolated from cultured human fibroblasts and HeLa cells on the basis of its ability to bind specifically to apurinic DNA. After separation from apurinic endonuclease activity, the protein was found to incorporate purine, but not pyrimidine, bases specifically into depurinated DNA so as to protect the apurinic sites from alkali. Purine base insertion activity was sensitive to heating and freezing as well as to caffeine and EDTA; it required K+ but not a divalent cation. Guanine, but not adenine, was incorporated into depurinated poly(dG-dC), whereas adenine, but not guanine, was incorporated into poly(dA-dT). After incorporation into depurinated DNA, guanine could be reisolated as dGMP. Although this activity suggests an alternative pathway for DNA repair that is independent of nucleotide excision, other functions for such an enzyme are possible.", "contents": "DNA binding activity from cultured human fibrolasts that is specific for partially depurinated DNA and that inserts purines into apurinic sites. A protein of molecular weight approximately 120,000 was isolated from cultured human fibroblasts and HeLa cells on the basis of its ability to bind specifically to apurinic DNA. After separation from apurinic endonuclease activity, the protein was found to incorporate purine, but not pyrimidine, bases specifically into depurinated DNA so as to protect the apurinic sites from alkali. Purine base insertion activity was sensitive to heating and freezing as well as to caffeine and EDTA; it required K+ but not a divalent cation. Guanine, but not adenine, was incorporated into depurinated poly(dG-dC), whereas adenine, but not guanine, was incorporated into poly(dA-dT). After incorporation into depurinated DNA, guanine could be reisolated as dGMP. Although this activity suggests an alternative pathway for DNA repair that is independent of nucleotide excision, other functions for such an enzyme are possible."}
{"id": "PMID:218193", "title": "Definition of cytochrome c binding domains by chemical modification: kinetics of reaction with beef mitochondrial reductase and functional organization of the respiratory chain.", "content": "An assay has been developed to study the steady-state kinetics of the reduction of cytochrome c by purified beef heart mitochondrial cytochrome c reductase (cytochrome bc(1) complex, complex III). An analogue of coenzyme Q(2) (2,3-dimethoxy-5-methyl-6-decylhydroquinone) was employed as an antimycin-sensitive reductant. The kinetics of reaction of ten different mono(4-carboxy-2,6-dinitrophenyl) derivatives of horse cytochrome c were determined. The modified proteins showed higher apparent K(m) values than the native protein and greater sensitivity to ionic strength, defining an interaction domain on cytochrome c for purified cytochrome c reductase. This interaction site is located on the front surface of the molecule (which contains the exposed heme edge) and surrounds the point at which the positive end of the dipole axis crosses the surface of the protein. The site is similar to that previously determined for mitochondrial cytochrome c oxidase and yeast cytochrome c peroxidase, suggesting that the primary interaction with redox partners is directed by the dipolar charge distribution on cytochrome c. The extensive overlapping of the interaction domains for the mitochondrial cytochrome c oxidase and reductase indicates that cytochrome c must be mobile in order to transfer electrons between them, depending on their relative positions in the membrane. Whether such mobility is necessary in intact mitochondria depends on whether the interactions with the complete membrane-bound system are the same as with the purified components.", "contents": "Definition of cytochrome c binding domains by chemical modification: kinetics of reaction with beef mitochondrial reductase and functional organization of the respiratory chain. An assay has been developed to study the steady-state kinetics of the reduction of cytochrome c by purified beef heart mitochondrial cytochrome c reductase (cytochrome bc(1) complex, complex III). An analogue of coenzyme Q(2) (2,3-dimethoxy-5-methyl-6-decylhydroquinone) was employed as an antimycin-sensitive reductant. The kinetics of reaction of ten different mono(4-carboxy-2,6-dinitrophenyl) derivatives of horse cytochrome c were determined. The modified proteins showed higher apparent K(m) values than the native protein and greater sensitivity to ionic strength, defining an interaction domain on cytochrome c for purified cytochrome c reductase. This interaction site is located on the front surface of the molecule (which contains the exposed heme edge) and surrounds the point at which the positive end of the dipole axis crosses the surface of the protein. The site is similar to that previously determined for mitochondrial cytochrome c oxidase and yeast cytochrome c peroxidase, suggesting that the primary interaction with redox partners is directed by the dipolar charge distribution on cytochrome c. The extensive overlapping of the interaction domains for the mitochondrial cytochrome c oxidase and reductase indicates that cytochrome c must be mobile in order to transfer electrons between them, depending on their relative positions in the membrane. Whether such mobility is necessary in intact mitochondria depends on whether the interactions with the complete membrane-bound system are the same as with the purified components."}
{"id": "PMID:218194", "title": "Low and high density lipoproteins and chylomicrons as regulators of rate of cholesterol synthesis in rat liver in vivo.", "content": "The steady-state levels of plasma cholesterol carried in high and low density lipoproteins and in chylomicrons were varied over a wide range by use of a constant-infusion technique. After 40 hr, the rates of hepatic cholesterol synthesis and levels of hepatic cholesterol esters were measured and were related to the plasma level of each of the lipoprotein fractions. From the rates of infusion and the steady-state plasma levels attained, the whole animal clearance rates for cholesterol carried in low density and high density lipoproteins and in chylomicrons were calculated to be 0.53, 0.61, and 42.6 ml/hr, respectively. Hepatic cholesterol ester content increased by 0.8 mug/g for each 1.0 mg/dl increase in the steady-state level of plasma low density lipoprotein cholesterol and by 1.4 mug/g for a similar elevation in plasma high density lipoprotein cholesterol. In contrast, the increase in ester content was 300-fold greater when chylomicrons were infused (330 mug/g). The rate of hepatic cholesterol synthesis was inhibited by a factor of 0.004 and 0.007, respectively, per 1.0 mg/dl increase in the steady-state level of plasma cholesterol carried in either low density or high density lipoprotein but the inhibition was by a factor of 0.255, 50-fold greater, when chylomicrons were infused. Thus, in the steady state, cholesterol carried in either low density or high density lipoproteins is apparently taken up by the liver and regulates the rate of hepatic cholesterol synthesis; however, cholesterol carried in chylomicrons is at least 50-fold more effective in this regard. This marked difference can be attributed to the much higher rates of transport of chylomicron cholesterol into the hepatocyte than of cholesterol carried in either low density or high density plasma lipoproteins.", "contents": "Low and high density lipoproteins and chylomicrons as regulators of rate of cholesterol synthesis in rat liver in vivo. The steady-state levels of plasma cholesterol carried in high and low density lipoproteins and in chylomicrons were varied over a wide range by use of a constant-infusion technique. After 40 hr, the rates of hepatic cholesterol synthesis and levels of hepatic cholesterol esters were measured and were related to the plasma level of each of the lipoprotein fractions. From the rates of infusion and the steady-state plasma levels attained, the whole animal clearance rates for cholesterol carried in low density and high density lipoproteins and in chylomicrons were calculated to be 0.53, 0.61, and 42.6 ml/hr, respectively. Hepatic cholesterol ester content increased by 0.8 mug/g for each 1.0 mg/dl increase in the steady-state level of plasma low density lipoprotein cholesterol and by 1.4 mug/g for a similar elevation in plasma high density lipoprotein cholesterol. In contrast, the increase in ester content was 300-fold greater when chylomicrons were infused (330 mug/g). The rate of hepatic cholesterol synthesis was inhibited by a factor of 0.004 and 0.007, respectively, per 1.0 mg/dl increase in the steady-state level of plasma cholesterol carried in either low density or high density lipoprotein but the inhibition was by a factor of 0.255, 50-fold greater, when chylomicrons were infused. Thus, in the steady state, cholesterol carried in either low density or high density lipoproteins is apparently taken up by the liver and regulates the rate of hepatic cholesterol synthesis; however, cholesterol carried in chylomicrons is at least 50-fold more effective in this regard. This marked difference can be attributed to the much higher rates of transport of chylomicron cholesterol into the hepatocyte than of cholesterol carried in either low density or high density plasma lipoproteins."}
{"id": "PMID:218195", "title": "An oligosaccharide-containing factor that induces cell differentiation in Dictyostelium discoideum.", "content": "When Dictyostelium discoideum amoebae (strain V12 M2) are spread at high density on agar containing 1 mM cyclic AMP, essentially all the cells differentiate into stalk cells after 2-3 days. We showed previously that isolated amoebae plated at low density on agar containing cyclic AMP do not differentiate, but can be induced to do so by a layer of high density helper cells from which they are separated by a thin cellophane membrane. We now show that the high density cell population releases a dialyzable factor that, in the presence of cyclic AMP, is capable of inducing isolated amoebae to differentiate into stalk cells. Sugar inhibition, sensitivity to glycosidases, and lectin affinity suggest that the differentiation-inducing activity requires the integrity of an oligosaccharide group containing sialic acid, L-fucose, and N-acetylgalactosamine. In addition, a phosphate group appears to be necessary for biological activity.", "contents": "An oligosaccharide-containing factor that induces cell differentiation in Dictyostelium discoideum. When Dictyostelium discoideum amoebae (strain V12 M2) are spread at high density on agar containing 1 mM cyclic AMP, essentially all the cells differentiate into stalk cells after 2-3 days. We showed previously that isolated amoebae plated at low density on agar containing cyclic AMP do not differentiate, but can be induced to do so by a layer of high density helper cells from which they are separated by a thin cellophane membrane. We now show that the high density cell population releases a dialyzable factor that, in the presence of cyclic AMP, is capable of inducing isolated amoebae to differentiate into stalk cells. Sugar inhibition, sensitivity to glycosidases, and lectin affinity suggest that the differentiation-inducing activity requires the integrity of an oligosaccharide group containing sialic acid, L-fucose, and N-acetylgalactosamine. In addition, a phosphate group appears to be necessary for biological activity."}
{"id": "PMID:218196", "title": "Involvement of spectrin in membrane fusion: induction of fusion in human erythrocyte ghosts by proteolytic enzymes and its inhibition by antispectrin antibody.", "content": "In contrast to intact human erythrocytes, human erythrocyte ghosts can be agglutinated but not fused by Sendai virus. Membrane fusion can, however, be induced in virus-agglutinated erythrocyte ghosts by addition of proteolytic enzymes such as trypsin, papain, or Pronase. When erythrocyte ghosts were reacted with antispectrin antiserum, the antiserum inhibited both the induction of fusion and the proteolysis of the membrane spectrin. The correlation between the membrane fusion process and the membrane cytoskeleton is discussed.", "contents": "Involvement of spectrin in membrane fusion: induction of fusion in human erythrocyte ghosts by proteolytic enzymes and its inhibition by antispectrin antibody. In contrast to intact human erythrocytes, human erythrocyte ghosts can be agglutinated but not fused by Sendai virus. Membrane fusion can, however, be induced in virus-agglutinated erythrocyte ghosts by addition of proteolytic enzymes such as trypsin, papain, or Pronase. When erythrocyte ghosts were reacted with antispectrin antiserum, the antiserum inhibited both the induction of fusion and the proteolysis of the membrane spectrin. The correlation between the membrane fusion process and the membrane cytoskeleton is discussed."}
{"id": "PMID:218197", "title": "Regulation of alkaline phosphatase expression in human choriocarcinoma cell lines.", "content": "The coincident expression of two structurally distinct isoenzymes of human alkaline phosphatase was demonstrated in two independently derived gestational choriocarcinoma cell lines. These proteins were shown to have enzymatic, antigenic, and physical-chemical properties resembling those of isoenzymes from term placenta and adult liver. The regulation of these isoenzymes has been studied during the exposure of both cell lines to 5-bromodeoxyuridine and dibutyryl cyclic AMP. The responses of the alkaline phosphatase isoenzymes to these agents have also been compared with the response of another protein phenotypic to placenta, the alpha subunit of chorionic gonadotropin. The results show that (i) the separate structural genes coding for placental and liver alkaline phosphatases are regulated in a noncoordinate fashion; (ii) both alkaline phosphatase genes respond independently of the alpha subunit; and (iii) the induction of the placental type isoenzyme occurs via at least two independent pathways.", "contents": "Regulation of alkaline phosphatase expression in human choriocarcinoma cell lines. The coincident expression of two structurally distinct isoenzymes of human alkaline phosphatase was demonstrated in two independently derived gestational choriocarcinoma cell lines. These proteins were shown to have enzymatic, antigenic, and physical-chemical properties resembling those of isoenzymes from term placenta and adult liver. The regulation of these isoenzymes has been studied during the exposure of both cell lines to 5-bromodeoxyuridine and dibutyryl cyclic AMP. The responses of the alkaline phosphatase isoenzymes to these agents have also been compared with the response of another protein phenotypic to placenta, the alpha subunit of chorionic gonadotropin. The results show that (i) the separate structural genes coding for placental and liver alkaline phosphatases are regulated in a noncoordinate fashion; (ii) both alkaline phosphatase genes respond independently of the alpha subunit; and (iii) the induction of the placental type isoenzyme occurs via at least two independent pathways."}
{"id": "PMID:218198", "title": "Binding site on macrophages that mediates uptake and degradation of acetylated low density lipoprotein, producing massive cholesterol deposition.", "content": "Resident mouse peritoneal macrophages were shown to take up and degrade acetylated (125)I-labeled low density lipoprotein ((125)I-acetyl-LDL) in vitro at rates that were 20-fold greater than those for the uptake and degradation of (125)I-LDL. The uptake of (125)I-acetyl-LDL and its subsequent degradation in lysosomes were attributable to a high-affinity, trypsin-sensitive, surface binding site that recognized acetyl-LDL but not native LDL. When (125)I-acetyl-LDL was bound to this site at 4 degrees C and the macrophages were subsequently warmed to 37 degrees C, 75% of the cell-bound radioactivity was degraded to mono[(125)I]iodotyrosine within 1 hr. The macrophage binding site also recognized maleylated LDL, maleylated albumin, and two sulfated polysaccharides (fucoidin and dextran sulfate) indicating that negative charges were important in the binding reaction. A similar binding site was present on rat peritoneal macrophages, guinea pig Kupffer cells, and cultured human monocytes but not on human lymphocytes or fibroblasts, mouse L cells or Y-1 adrenal cells, or Chinese hamster ovary cells. Uptake and degradation of acetyl-LDL via this binding site stimulated cholesterol esterification 100-fold and produced a 38-fold increase in the cellular content of cholesterol in mouse peritoneal macrophages. Although the physiologic significance, if any, of this macrophage uptake mechanism is not yet known, we hypothesize that it may mediate the degradation of denatured LDL in the body and thus serve as a \"backup\" mechanism for the previously described receptor-mediated degradation of native LDL that occurs in parenchymal cells. Such a scavenger pathway might account for the widespread deposition of LDL-derived cholesteryl esters in macrophages of patients with familial hypercholesterolemia in whom the parenchymal cell pathway for LDL degradation is blocked, owing to a genetic deficiency of receptors for native LDL.", "contents": "Binding site on macrophages that mediates uptake and degradation of acetylated low density lipoprotein, producing massive cholesterol deposition. Resident mouse peritoneal macrophages were shown to take up and degrade acetylated (125)I-labeled low density lipoprotein ((125)I-acetyl-LDL) in vitro at rates that were 20-fold greater than those for the uptake and degradation of (125)I-LDL. The uptake of (125)I-acetyl-LDL and its subsequent degradation in lysosomes were attributable to a high-affinity, trypsin-sensitive, surface binding site that recognized acetyl-LDL but not native LDL. When (125)I-acetyl-LDL was bound to this site at 4 degrees C and the macrophages were subsequently warmed to 37 degrees C, 75% of the cell-bound radioactivity was degraded to mono[(125)I]iodotyrosine within 1 hr. The macrophage binding site also recognized maleylated LDL, maleylated albumin, and two sulfated polysaccharides (fucoidin and dextran sulfate) indicating that negative charges were important in the binding reaction. A similar binding site was present on rat peritoneal macrophages, guinea pig Kupffer cells, and cultured human monocytes but not on human lymphocytes or fibroblasts, mouse L cells or Y-1 adrenal cells, or Chinese hamster ovary cells. Uptake and degradation of acetyl-LDL via this binding site stimulated cholesterol esterification 100-fold and produced a 38-fold increase in the cellular content of cholesterol in mouse peritoneal macrophages. Although the physiologic significance, if any, of this macrophage uptake mechanism is not yet known, we hypothesize that it may mediate the degradation of denatured LDL in the body and thus serve as a \"backup\" mechanism for the previously described receptor-mediated degradation of native LDL that occurs in parenchymal cells. Such a scavenger pathway might account for the widespread deposition of LDL-derived cholesteryl esters in macrophages of patients with familial hypercholesterolemia in whom the parenchymal cell pathway for LDL degradation is blocked, owing to a genetic deficiency of receptors for native LDL."}
{"id": "PMID:218199", "title": "Is the product of the src gene a promoter?", "content": "Addition of a potent promoter, 12-O-tetradecanoylphorbol 13-acetate (TPA), to primary avian tendon or chicken embryo fibroblast cells infected with a temperature-sensitive mutant of Rous sarcoma virus produced a complete transformed phenocopy at the nonpermissive temperature by the criteria tested. While normal, uninfected cultures also shifted towards a transformed phenotype after TPA addition, they did not achieve the same degree of morphological and biochemical alteration seen in virus-infected, TPA-treated cells. It is proposed that viral carcinogenesis, despite its rapidity, may occur in two stages: an \"initiation\" step caused by expression of a part of viral genome other than src (or by integration) and a promotion step (itself a multistep process) caused by the activation of the src gene. The src gene product could be enhanced or replaced by other promoting agents.", "contents": "Is the product of the src gene a promoter? Addition of a potent promoter, 12-O-tetradecanoylphorbol 13-acetate (TPA), to primary avian tendon or chicken embryo fibroblast cells infected with a temperature-sensitive mutant of Rous sarcoma virus produced a complete transformed phenocopy at the nonpermissive temperature by the criteria tested. While normal, uninfected cultures also shifted towards a transformed phenotype after TPA addition, they did not achieve the same degree of morphological and biochemical alteration seen in virus-infected, TPA-treated cells. It is proposed that viral carcinogenesis, despite its rapidity, may occur in two stages: an \"initiation\" step caused by expression of a part of viral genome other than src (or by integration) and a promotion step (itself a multistep process) caused by the activation of the src gene. The src gene product could be enhanced or replaced by other promoting agents."}
{"id": "PMID:218200", "title": "Recognition of differentiation antigens of spermatogenesis in the mouse by using antibodies from spleen cell-myeloma hybrids after syngeneic immunization.", "content": "Two differentiation antigens of spermatogenesis in the mouse are defined by monoclonal antibodies from hybridomas produced between the myeloma P3-X63Ag8 and spleen lymphocytes immunized with syngeneic testis cells. These antigens are on testis cells, and not liver, kidney, brain, spleen, or whole ovary. They are species but not strain specific and trypsin sensitive but collagenase insensitive. On the basis of their appearance during the onset of spermatogenesis they appear to be differentiation antigens expressed during different but overlapping time windows during spermatogenesis.", "contents": "Recognition of differentiation antigens of spermatogenesis in the mouse by using antibodies from spleen cell-myeloma hybrids after syngeneic immunization. Two differentiation antigens of spermatogenesis in the mouse are defined by monoclonal antibodies from hybridomas produced between the myeloma P3-X63Ag8 and spleen lymphocytes immunized with syngeneic testis cells. These antigens are on testis cells, and not liver, kidney, brain, spleen, or whole ovary. They are species but not strain specific and trypsin sensitive but collagenase insensitive. On the basis of their appearance during the onset of spermatogenesis they appear to be differentiation antigens expressed during different but overlapping time windows during spermatogenesis."}
{"id": "PMID:218201", "title": "In vitro suppression of UAG and UGA mutants in the thymidine kinase gene of herpes simplex virus.", "content": "We have studied the in vitro translation, in nuclease-treated reticulocyte lysates, of mRNA from cells infected with several thymidine kinase-deficient mutants of herpes simplex virus type I. The addition of suppressor tRNAs from yeast resulted in suppression of the mutant property in the case of two mutants. Synthesis of enzymatically active viral thymidine kinase was restored by serine-inserting amber suppressor tRNA in the case of HSV TK4- and synthesis of the intact, but inactive, thymidine kinase protein was restored by serine- and leucine-inserting UGA suppressor tRNAs in the case of HSV TK43-. Read-through of the normal termination at the end of the thymidine kinase gene was promoted by UGA suppressor tRNAs. We conclude that HSV-TK4- is an amber (UAG) mutant and that HSV-TK43- is an opal (UGA) mutant.", "contents": "In vitro suppression of UAG and UGA mutants in the thymidine kinase gene of herpes simplex virus. We have studied the in vitro translation, in nuclease-treated reticulocyte lysates, of mRNA from cells infected with several thymidine kinase-deficient mutants of herpes simplex virus type I. The addition of suppressor tRNAs from yeast resulted in suppression of the mutant property in the case of two mutants. Synthesis of enzymatically active viral thymidine kinase was restored by serine-inserting amber suppressor tRNA in the case of HSV TK4- and synthesis of the intact, but inactive, thymidine kinase protein was restored by serine- and leucine-inserting UGA suppressor tRNAs in the case of HSV TK43-. Read-through of the normal termination at the end of the thymidine kinase gene was promoted by UGA suppressor tRNAs. We conclude that HSV-TK4- is an amber (UAG) mutant and that HSV-TK43- is an opal (UGA) mutant."}
{"id": "PMID:218202", "title": "Generation of cytolytic T lymphocytes after reovirus infection: role of S1 gene.", "content": "Cytotoxic T lymphocytes (CTLs) can be generated if spleen cells from reovirus-infected mice are stimulated in vitro with syngeneic reovirus-infected cells. These cytolytic effector cells demonstrate: (i) serotype specificity (i.e., maximal cytolytic activity is observed on target cells infected with the serotype used to induce the CTLs) and (ii) H-2 restriction. The SI gene was shown to be the predominant viral gene determining the specificity of the cytotoxic T cells. This genome segment has previously been demonstrated to encode the viral hemagglutinin and determines reovirus cell tropism in the nervous system.", "contents": "Generation of cytolytic T lymphocytes after reovirus infection: role of S1 gene. Cytotoxic T lymphocytes (CTLs) can be generated if spleen cells from reovirus-infected mice are stimulated in vitro with syngeneic reovirus-infected cells. These cytolytic effector cells demonstrate: (i) serotype specificity (i.e., maximal cytolytic activity is observed on target cells infected with the serotype used to induce the CTLs) and (ii) H-2 restriction. The SI gene was shown to be the predominant viral gene determining the specificity of the cytotoxic T cells. This genome segment has previously been demonstrated to encode the viral hemagglutinin and determines reovirus cell tropism in the nervous system."}
{"id": "PMID:218203", "title": "Rapid turnover of acetyl groups in the four core histones of simian virus 40 minichromosomes.", "content": "The four core histones (H2a, H2b, H3, and H4) bound to simian virus 40 minichromosomes isolated from infected cells contain rapidly labeled acetyl groups in internal positions of the histone polypeptide chain. Upon chase, these acetyl residues decay with a half-life of less than 15 min. The acetyl groups are incorporated in histones bound to mature chromosomes and not in newly synthesized histones bound to replicating viral chromosomes. The rate of acetate incorporation is not related to the degree of steady state acetylation of the individual viral or cellular histones. This rate is 4-fold higher for the viral chromatin than for its cellular counterpart isolated from the same nuclei. The possible role for histone acetylation in viral genome expression is discussed.", "contents": "Rapid turnover of acetyl groups in the four core histones of simian virus 40 minichromosomes. The four core histones (H2a, H2b, H3, and H4) bound to simian virus 40 minichromosomes isolated from infected cells contain rapidly labeled acetyl groups in internal positions of the histone polypeptide chain. Upon chase, these acetyl residues decay with a half-life of less than 15 min. The acetyl groups are incorporated in histones bound to mature chromosomes and not in newly synthesized histones bound to replicating viral chromosomes. The rate of acetate incorporation is not related to the degree of steady state acetylation of the individual viral or cellular histones. This rate is 4-fold higher for the viral chromatin than for its cellular counterpart isolated from the same nuclei. The possible role for histone acetylation in viral genome expression is discussed."}
{"id": "PMID:218204", "title": "Enkephalin inhibits release of substance P from sensory neurons in culture and decreases action potential duration.", "content": "Sensory neurons grown in dispersed cell culture in the absence of non-neuronal cell types contain immunoreactive substance P that is chemically similar to synthetic substance P. When depolarized in high-K+ media (30-120 mM), the neurons release this peptide by a Ca2+-dependent mechanism. An enkephalin analogue, [D-Ala2]enkephalin amide, at 10 micron inhibits the K+-evoked release of substance P. At the same or lower concentrations, [D-Ala2]enkephalin amide and enkephalin decrease the duration of the Ca2+ action potential evoked and recorded in dorsal root ganglion cell bodies without affecting the resting membrane potential or resting membrane conductance. This modulation of voltage-sensitive channels may account for the inhibition of substance P release.", "contents": "Enkephalin inhibits release of substance P from sensory neurons in culture and decreases action potential duration. Sensory neurons grown in dispersed cell culture in the absence of non-neuronal cell types contain immunoreactive substance P that is chemically similar to synthetic substance P. When depolarized in high-K+ media (30-120 mM), the neurons release this peptide by a Ca2+-dependent mechanism. An enkephalin analogue, [D-Ala2]enkephalin amide, at 10 micron inhibits the K+-evoked release of substance P. At the same or lower concentrations, [D-Ala2]enkephalin amide and enkephalin decrease the duration of the Ca2+ action potential evoked and recorded in dorsal root ganglion cell bodies without affecting the resting membrane potential or resting membrane conductance. This modulation of voltage-sensitive channels may account for the inhibition of substance P release."}
{"id": "PMID:218205", "title": "Semisynthetic horse heart [65-homoserine]cytochrome c from three fragments.", "content": "Horse heart cytochrome c was treated with methylsulfonylethyloxycarbonyl succinimide (Msc-ONSu) to give fully N(epsilon)-protected cytochrome c. Treatment of this derivative with a hard base for 15 sec regenerated the native tetrahectapeptide chain. CNBr degradation of the protected compound produced three fragments bearing only protective Msc functions on epsilon-amino groups. The fragment comprising the sequence 81-104 was isolated from the mixture and acylated with N-hydroxysuccinimidyl-t-butyloxycarbonyl-L-methioninate. The resulting pentacosapeptide derivative was partially deprotected by treatment with acid and condensed in good yield (65%) with fully synthetic N(alpha66), N(epsilon72,73,79)- tetra-Msc-cytochrome-c-(66-79)-tetradecapeptide azide. This pathway is preferred because the pentadecapeptide azide derivative 66-80 acylated the N(epsilon)-protected tetracosapeptide sequence 81-104 in an unpredictable manner. Subsequent treatment of the product with a base produced unprotected semisynthetic cytochrome-c-(66-104)-nonatriacontapeptide, which is known to undergo acylation by unprotected [Hse(65)]cytochrome-c-(1-65)-pentahexacontapeptide lactone. The high specificity of this condensation is ascribed to \"conformation direction.\" Semisynthetic [Hse(65)]cytochrome c thus prepared reacts like native cytochrome c with a succinate cytochrome c reductase preparation and with cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1). This semisynthetic strategy may provide a rapid route for the production of cytochrome c analogs modified in the highly conservative sequence 66-80.", "contents": "Semisynthetic horse heart [65-homoserine]cytochrome c from three fragments. Horse heart cytochrome c was treated with methylsulfonylethyloxycarbonyl succinimide (Msc-ONSu) to give fully N(epsilon)-protected cytochrome c. Treatment of this derivative with a hard base for 15 sec regenerated the native tetrahectapeptide chain. CNBr degradation of the protected compound produced three fragments bearing only protective Msc functions on epsilon-amino groups. The fragment comprising the sequence 81-104 was isolated from the mixture and acylated with N-hydroxysuccinimidyl-t-butyloxycarbonyl-L-methioninate. The resulting pentacosapeptide derivative was partially deprotected by treatment with acid and condensed in good yield (65%) with fully synthetic N(alpha66), N(epsilon72,73,79)- tetra-Msc-cytochrome-c-(66-79)-tetradecapeptide azide. This pathway is preferred because the pentadecapeptide azide derivative 66-80 acylated the N(epsilon)-protected tetracosapeptide sequence 81-104 in an unpredictable manner. Subsequent treatment of the product with a base produced unprotected semisynthetic cytochrome-c-(66-104)-nonatriacontapeptide, which is known to undergo acylation by unprotected [Hse(65)]cytochrome-c-(1-65)-pentahexacontapeptide lactone. The high specificity of this condensation is ascribed to \"conformation direction.\" Semisynthetic [Hse(65)]cytochrome c thus prepared reacts like native cytochrome c with a succinate cytochrome c reductase preparation and with cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1). This semisynthetic strategy may provide a rapid route for the production of cytochrome c analogs modified in the highly conservative sequence 66-80."}
{"id": "PMID:218206", "title": "Novel protein kinase, AUT-PK 85, isolated from adrenocortical carcinoma: purification and characterization.", "content": "We describe the purification to apparent homogeneity of a protein kinase (designated AUT-PK 85) from adrenocortical carcinoma 494, as evidenced by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The enzyme binds cyclic AMP (cAMP) and autophosphorylates but does not use histone, casein, or polysomes as substrates in the presence or absence of cAMP. Stoichiometry of phosphate incorporation was 0.71 mol/mol of enzyme. The enzyme was found to have a molecular weight of 85,000 based on gel filtration. The protein was composed of polypeptides having the same molecular weight 42,000, and thus it appears to consist of two subunits of equal size. The enzyme bound two cAMP molecules, indicating that each subunit binds one molecule of cAMP. The homogeneous enzyme did not inhibit the protein kinase activity of the free catalytic subunit of normal adrenal cAMP-dependent protein kinase under conditions such that recombination with the free regulatory subunit occurred. cAMP bound specifically to the enzyme with an apparent dissociation constant (cfKd) of 1.2 X 10(-8) M. Scatchard plot data indicated one type of binding sites for cAMP. The enzyme did not bind adenosine. This novel autophosphorylating, cAMP-binding, protein kinase may be a characteristic of certain adrenal neoplasms.", "contents": "Novel protein kinase, AUT-PK 85, isolated from adrenocortical carcinoma: purification and characterization. We describe the purification to apparent homogeneity of a protein kinase (designated AUT-PK 85) from adrenocortical carcinoma 494, as evidenced by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The enzyme binds cyclic AMP (cAMP) and autophosphorylates but does not use histone, casein, or polysomes as substrates in the presence or absence of cAMP. Stoichiometry of phosphate incorporation was 0.71 mol/mol of enzyme. The enzyme was found to have a molecular weight of 85,000 based on gel filtration. The protein was composed of polypeptides having the same molecular weight 42,000, and thus it appears to consist of two subunits of equal size. The enzyme bound two cAMP molecules, indicating that each subunit binds one molecule of cAMP. The homogeneous enzyme did not inhibit the protein kinase activity of the free catalytic subunit of normal adrenal cAMP-dependent protein kinase under conditions such that recombination with the free regulatory subunit occurred. cAMP bound specifically to the enzyme with an apparent dissociation constant (cfKd) of 1.2 X 10(-8) M. Scatchard plot data indicated one type of binding sites for cAMP. The enzyme did not bind adenosine. This novel autophosphorylating, cAMP-binding, protein kinase may be a characteristic of certain adrenal neoplasms."}
{"id": "PMID:218207", "title": "Deletion mutants of simian virus 40 defective in biosynthesis of late viral mRNA.", "content": "Deletion mutants of simian virus 40 defective in late gene functions have been examined for genetic elements that control the biosynthesis of the viral mRNAs. Mutant-specific RNA from infected cells was identified by CH3Hg/(OH)/agarose gel electrophoresis and mapped by the nuclease S1 technique. Altered RNA species, shortened by a size equivalent to the deletion region, can be detected in cells infected with these mutants lacking sequences within the body RNA segments. On the other hand, mutants that lack the 5'-end of the body sequences (a splice junction) fail to accumulate the respective shortened RNA species. In particular, mutant dl-2301 whose deletion includes both the leader and body splice junctions plus the intervening sequences, exhibits a polar effect on a distal gene. Whereas the late region of dl-2301 can be transcribed normally, the mutant defect appears to be associated with little or no accumulation of the mutant-specific late RNA in the infected cells. These results suggest that splice junctions or the intervening sequences, or both, in the viral genome are control signals for post-transcriptional processing of the viral RNA.", "contents": "Deletion mutants of simian virus 40 defective in biosynthesis of late viral mRNA. Deletion mutants of simian virus 40 defective in late gene functions have been examined for genetic elements that control the biosynthesis of the viral mRNAs. Mutant-specific RNA from infected cells was identified by CH3Hg/(OH)/agarose gel electrophoresis and mapped by the nuclease S1 technique. Altered RNA species, shortened by a size equivalent to the deletion region, can be detected in cells infected with these mutants lacking sequences within the body RNA segments. On the other hand, mutants that lack the 5'-end of the body sequences (a splice junction) fail to accumulate the respective shortened RNA species. In particular, mutant dl-2301 whose deletion includes both the leader and body splice junctions plus the intervening sequences, exhibits a polar effect on a distal gene. Whereas the late region of dl-2301 can be transcribed normally, the mutant defect appears to be associated with little or no accumulation of the mutant-specific late RNA in the infected cells. These results suggest that splice junctions or the intervening sequences, or both, in the viral genome are control signals for post-transcriptional processing of the viral RNA."}
{"id": "PMID:218208", "title": "Nucleotide sequence of the BK virus DNA segment encoding small t antigen.", "content": "The nucleotide sequence from 0.64 to 0.53 map units in the BK virus genome coding for the small t protein has been determined. There is only one open reading frame that can code for a polypeptide of 172 amino acids, the putative small t protein. Beyond this segment, multiple termination codons are present in all three reading frames. There is considerable nucleotide and amino acid sequence homology between this region of BK virus and the analogous region of simian virus 40, especially in the proximal portion from 0.64 to 0.60 map units which is most likely common to the small t and large T BK virus proteins. A comparison of the conserved sequences within the early papovavirus genes both confirms the evolutionary relationship between these viruses and suggests the amino acid composition of the regions required for T antigen functions.", "contents": "Nucleotide sequence of the BK virus DNA segment encoding small t antigen. The nucleotide sequence from 0.64 to 0.53 map units in the BK virus genome coding for the small t protein has been determined. There is only one open reading frame that can code for a polypeptide of 172 amino acids, the putative small t protein. Beyond this segment, multiple termination codons are present in all three reading frames. There is considerable nucleotide and amino acid sequence homology between this region of BK virus and the analogous region of simian virus 40, especially in the proximal portion from 0.64 to 0.60 map units which is most likely common to the small t and large T BK virus proteins. A comparison of the conserved sequences within the early papovavirus genes both confirms the evolutionary relationship between these viruses and suggests the amino acid composition of the regions required for T antigen functions."}
{"id": "PMID:218209", "title": "Synthesis and assembly of membrane glycoproteins: presence of leader peptide in nonglycosylated precursor of membrane glycoprotein of vesicular stomatitis virus.", "content": "Translation of mRNA encoding vesicular stomatitis virus envelope glycoprotein G by as membrane-free ribosomal extract obtained from HeLa cells yielded a nonglycosylated protein (G1 (Mr 63,000). In the presence of added microsomal membranes, G1 was converted to the glycosylated protein (G2 (Mr 67,000) which is inserted in the membrane vesicles as a transmembrane protein. Labeling with methionine donated by wheat germ initiator tRNA1Met showed that G1 but not G2 contains methionine in the NH2-terminal position. Determination of the NH2-terminal sequence of G1, G2, and G showed that a leader peptide of 16 amino acids is present in G1 but absent from the glycosylated proteins G2 and G. This leader peptide contains at least 62% hydrophobic amino acids and is removed presumably during insertion of G1 into the membrane.", "contents": "Synthesis and assembly of membrane glycoproteins: presence of leader peptide in nonglycosylated precursor of membrane glycoprotein of vesicular stomatitis virus. Translation of mRNA encoding vesicular stomatitis virus envelope glycoprotein G by as membrane-free ribosomal extract obtained from HeLa cells yielded a nonglycosylated protein (G1 (Mr 63,000). In the presence of added microsomal membranes, G1 was converted to the glycosylated protein (G2 (Mr 67,000) which is inserted in the membrane vesicles as a transmembrane protein. Labeling with methionine donated by wheat germ initiator tRNA1Met showed that G1 but not G2 contains methionine in the NH2-terminal position. Determination of the NH2-terminal sequence of G1, G2, and G showed that a leader peptide of 16 amino acids is present in G1 but absent from the glycosylated proteins G2 and G. This leader peptide contains at least 62% hydrophobic amino acids and is removed presumably during insertion of G1 into the membrane."}
{"id": "PMID:218210", "title": "Structure of poly(adenosine diphosphate ribose): identification of 2'-[1''-ribosyl-2''-(or 3''-)(1'''-ribosyl)]adenosine-5',5'',5'''-tris(phosphate) as a branch linkage.", "content": "Poly([14C]adenosine diphosphate ribose) was synthesized from [14C]NAD+ with calf thymus nuclei. The fraction containing poly(adenosine diphosphate ribose) eluted with 0.22--0.40 M phosphate buffer (pH 6.8) from a hydroxylapatite column, was completely hydrolyzed with venom phosphodiesterase, and was separated by DEAE-Sephadex A-25 column chromatography in 7 M urea. A new compound, which constituted 2% of the products from poly(adenosine diphosphate ribose), was found in addition to the expected products--i.e., 5'-AMP, 2'-(1''-ribosyl)adenosine-5',5''-bis(phosphate), and its derivatives. This compound was identified as 2'-[1''-ribosyl 2''-(or 3''-)(1'''-ribosyl)]adenosine-5',5'',5'''-tris(phosphate). The existence of this compound is evidence of a branching structure of poly(adenosine diphosphate ribose), which was previously thought to be a linear molecule. The content of this compound suggests that the frequency of branching is about 1 per 20--30 adenosine diphosphate ribose residues of high molecular weight poly(adenosine diphosphate ribose).", "contents": "Structure of poly(adenosine diphosphate ribose): identification of 2'-[1''-ribosyl-2''-(or 3''-)(1'''-ribosyl)]adenosine-5',5'',5'''-tris(phosphate) as a branch linkage. Poly([14C]adenosine diphosphate ribose) was synthesized from [14C]NAD+ with calf thymus nuclei. The fraction containing poly(adenosine diphosphate ribose) eluted with 0.22--0.40 M phosphate buffer (pH 6.8) from a hydroxylapatite column, was completely hydrolyzed with venom phosphodiesterase, and was separated by DEAE-Sephadex A-25 column chromatography in 7 M urea. A new compound, which constituted 2% of the products from poly(adenosine diphosphate ribose), was found in addition to the expected products--i.e., 5'-AMP, 2'-(1''-ribosyl)adenosine-5',5''-bis(phosphate), and its derivatives. This compound was identified as 2'-[1''-ribosyl 2''-(or 3''-)(1'''-ribosyl)]adenosine-5',5'',5'''-tris(phosphate). The existence of this compound is evidence of a branching structure of poly(adenosine diphosphate ribose), which was previously thought to be a linear molecule. The content of this compound suggests that the frequency of branching is about 1 per 20--30 adenosine diphosphate ribose residues of high molecular weight poly(adenosine diphosphate ribose)."}
{"id": "PMID:218211", "title": "Opiates and enkephalins inhibit synthesis of gangliosides and membrane glycoproteins in mouse neuroblastoma cell line N4TG1.", "content": "When mouse neuroblastoma clonal cell line N4TG1 cells were cultured in the presence of opiates or enkephalins, in the range 10(-6)-10(-10) M for 24 hr, a dose-dependent inhibition of the incorporation of [3H]glucosamine and [14C]-galactose into sialoglycosphingolipids and glycoproteins was observed. The gangliosides most affected comigrated in thinlayer chromatographic systems with GM2 (GalNAc[AcNeu]-Gal-Glc-ceramide), GM1 (Gal-GalNAc[AcNeu]Gal-Glc-ceramide), and GDla (AcNeu-Gal-GalNAc[AcNeu]Gal-Glc-ceramide). The effects were stereospecific and naloxone-reversible. Polyacrylamide gel electrophoresis revealed that the synthesis of a large number of membrane glycoproteins was also stereospecifically inhibited. Synthesis of other proteins and glycoproteins, proteoglycans, DNA, and membrane phospholipids and the rate of cell division were not altered in any specific or stereospecific manner. Moreover, clonal cell lines (neuroblastomas and oligodendroglioma) and human skin fibroblasts, which do not possess opiate receptors, did not respond to opiates or enkephalins in a stereospecific manner.", "contents": "Opiates and enkephalins inhibit synthesis of gangliosides and membrane glycoproteins in mouse neuroblastoma cell line N4TG1. When mouse neuroblastoma clonal cell line N4TG1 cells were cultured in the presence of opiates or enkephalins, in the range 10(-6)-10(-10) M for 24 hr, a dose-dependent inhibition of the incorporation of [3H]glucosamine and [14C]-galactose into sialoglycosphingolipids and glycoproteins was observed. The gangliosides most affected comigrated in thinlayer chromatographic systems with GM2 (GalNAc[AcNeu]-Gal-Glc-ceramide), GM1 (Gal-GalNAc[AcNeu]Gal-Glc-ceramide), and GDla (AcNeu-Gal-GalNAc[AcNeu]Gal-Glc-ceramide). The effects were stereospecific and naloxone-reversible. Polyacrylamide gel electrophoresis revealed that the synthesis of a large number of membrane glycoproteins was also stereospecifically inhibited. Synthesis of other proteins and glycoproteins, proteoglycans, DNA, and membrane phospholipids and the rate of cell division were not altered in any specific or stereospecific manner. Moreover, clonal cell lines (neuroblastomas and oligodendroglioma) and human skin fibroblasts, which do not possess opiate receptors, did not respond to opiates or enkephalins in a stereospecific manner."}
{"id": "PMID:218212", "title": "Enzymatic activities associated with a purified simian virus 40 T antigen-related protein.", "content": "A protein antigenically related to the simian virus (SV 40) A gene product has been purified to near homogeneity from cells infected with the adenovirus-SV 40 hybrid virus Ad2(+)D2 and shown to contain ATPase (ATP phosphohydrolase, EC 3.6.1.3) and protein kinase (ATP:phosphotransferase, EC 2.7.1.37) activity. Both enzymatic activities copurify with the protein through six stages including one gel filtration column, two ion exchange columns, and a heparin affinity column. Analogous fractions from extracts of cells uninfected or infected with adenovirus 2 alone do not contain these enzymatic activities. The D2 hybrid protein resolves into two forms (I and II) during ion exchange chromatography. Form I, the major species (85%) of the D2 hybrid protein, elutes from DEAE-Sephadex in 0.37 M NaCl and is able to catalyze the hydrolysis of ATP to ADP + P(i) at a rate of 3 mumol/hr per mg. The remaining 10-15% of the D2 hybrid protein consists of form II which elutes from DEAE-Sephadex in 0.29 M NaCl and is able to hydrolyze ATP as well as to incorporate phosphorus from ATP into either the D2 hybrid protein itself or other protein acceptors such as phosvitin. Although both forms are able to bind DNA, the ATPase activity of form I cosediments with SV 40 DNA more efficiently than does the protein kinase activity of form II during glycerol gradient centrifugation. The ATPase activity of form I is efficiently inhibited by addition of anti-T gamma globulin to the reaction mixture whereas control gamma globulin has no effect. Similarly, the phosphorylation of the D2 hybrid protein by form II is inhibited by anti-T gamma globulin. By contrast, phosphorylation of phosvitin is specifically inhibited by antibody only when the immune complex is removed from the reaction mixture. Thus, it appears likely that one and possibly two enzymatic activities are carried out by the D2 hybrid protein. These findings are discussed in terms of mechanisms of SV 40 DNA replication and virally induced transformation.", "contents": "Enzymatic activities associated with a purified simian virus 40 T antigen-related protein. A protein antigenically related to the simian virus (SV 40) A gene product has been purified to near homogeneity from cells infected with the adenovirus-SV 40 hybrid virus Ad2(+)D2 and shown to contain ATPase (ATP phosphohydrolase, EC 3.6.1.3) and protein kinase (ATP:phosphotransferase, EC 2.7.1.37) activity. Both enzymatic activities copurify with the protein through six stages including one gel filtration column, two ion exchange columns, and a heparin affinity column. Analogous fractions from extracts of cells uninfected or infected with adenovirus 2 alone do not contain these enzymatic activities. The D2 hybrid protein resolves into two forms (I and II) during ion exchange chromatography. Form I, the major species (85%) of the D2 hybrid protein, elutes from DEAE-Sephadex in 0.37 M NaCl and is able to catalyze the hydrolysis of ATP to ADP + P(i) at a rate of 3 mumol/hr per mg. The remaining 10-15% of the D2 hybrid protein consists of form II which elutes from DEAE-Sephadex in 0.29 M NaCl and is able to hydrolyze ATP as well as to incorporate phosphorus from ATP into either the D2 hybrid protein itself or other protein acceptors such as phosvitin. Although both forms are able to bind DNA, the ATPase activity of form I cosediments with SV 40 DNA more efficiently than does the protein kinase activity of form II during glycerol gradient centrifugation. The ATPase activity of form I is efficiently inhibited by addition of anti-T gamma globulin to the reaction mixture whereas control gamma globulin has no effect. Similarly, the phosphorylation of the D2 hybrid protein by form II is inhibited by anti-T gamma globulin. By contrast, phosphorylation of phosvitin is specifically inhibited by antibody only when the immune complex is removed from the reaction mixture. Thus, it appears likely that one and possibly two enzymatic activities are carried out by the D2 hybrid protein. These findings are discussed in terms of mechanisms of SV 40 DNA replication and virally induced transformation."}
{"id": "PMID:218213", "title": "Parvovirus RNA transcripts containing sequences not present in mature mRNA: a method for isolation of putative mRNA precursor sequences.", "content": "We report here a method of RNA preparation that may enrich for precursor RNA sequences and the results of an investigation of adeno-associated virus (AAV) RNA transcription that used this method. Whole cells were lysed with detergent and high salt and separated into supernatant and pellet (crude chromatin) fractions. These fractions were then separately deproteinized by proteolytic digestion and phenol extractions. DNA was removed from the preparation by two cycles of pancreatic DNase digestion and phenol extraction. Hybridization analyses of the RNA obtained from AAV/adenovirus-infected KB (human) cells revealed some AAV-specific RNA sequences that were not present in the mature 20S mRNA. These additional sequences were contained in AAV RNA molecules present in the pellet fraction, whereas the 20S AAV mRNA accumulated in the supernatant. A species of AAV-specific RNA (about 22S), which was associated only with the pellet fraction and was labeled only after a short pulse, appeared to have a kinetic relationship with the more stable cytoplasmic 20S mRNA. These putative AAV mRNA \"precursors\" and precursor sequences were not observed previously when conventional methods were used to obtain RNA from either whole cells or isolated nuclei.", "contents": "Parvovirus RNA transcripts containing sequences not present in mature mRNA: a method for isolation of putative mRNA precursor sequences. We report here a method of RNA preparation that may enrich for precursor RNA sequences and the results of an investigation of adeno-associated virus (AAV) RNA transcription that used this method. Whole cells were lysed with detergent and high salt and separated into supernatant and pellet (crude chromatin) fractions. These fractions were then separately deproteinized by proteolytic digestion and phenol extractions. DNA was removed from the preparation by two cycles of pancreatic DNase digestion and phenol extraction. Hybridization analyses of the RNA obtained from AAV/adenovirus-infected KB (human) cells revealed some AAV-specific RNA sequences that were not present in the mature 20S mRNA. These additional sequences were contained in AAV RNA molecules present in the pellet fraction, whereas the 20S AAV mRNA accumulated in the supernatant. A species of AAV-specific RNA (about 22S), which was associated only with the pellet fraction and was labeled only after a short pulse, appeared to have a kinetic relationship with the more stable cytoplasmic 20S mRNA. These putative AAV mRNA \"precursors\" and precursor sequences were not observed previously when conventional methods were used to obtain RNA from either whole cells or isolated nuclei."}
{"id": "PMID:218214", "title": "Vasoactive intestinal polypeptide: specific binding to rat brain membranes.", "content": "The binding of radiolabeled vasoactive intestinal polypeptide (VIP) to rat brain membranes was investigated. Specific binding of 125I-labeled VIP was reversible and saturable (Bmax = 2.2 pmol/g of wet tissue). Brain membranes exhibited a high affinity for 125I-labeled VIP (KD = 1 nM) at a single class of noninteracting sites. Binding of 125I-labeled VIP paralleled its immunohistochemical localization, being enriched in cerebral cortex, hippocampus, striatum, and thalamus, with the notable exception of the hypothalamus, which had low levels of binding. The density of sites was greater in synaptosomal fractions relative to mitochondrial or nuclear fractions. Secretin and partial sequences of it and VIP inhibited binding to brain membranes with an order of potency similar to that found in other systems. The findings suggest the existence of a unique new class of brain receptors.", "contents": "Vasoactive intestinal polypeptide: specific binding to rat brain membranes. The binding of radiolabeled vasoactive intestinal polypeptide (VIP) to rat brain membranes was investigated. Specific binding of 125I-labeled VIP was reversible and saturable (Bmax = 2.2 pmol/g of wet tissue). Brain membranes exhibited a high affinity for 125I-labeled VIP (KD = 1 nM) at a single class of noninteracting sites. Binding of 125I-labeled VIP paralleled its immunohistochemical localization, being enriched in cerebral cortex, hippocampus, striatum, and thalamus, with the notable exception of the hypothalamus, which had low levels of binding. The density of sites was greater in synaptosomal fractions relative to mitochondrial or nuclear fractions. Secretin and partial sequences of it and VIP inhibited binding to brain membranes with an order of potency similar to that found in other systems. The findings suggest the existence of a unique new class of brain receptors."}
{"id": "PMID:218215", "title": "Integration and transcription of mouse mammary tumor virus DNA in rat hepatoma cells.", "content": "Rat hepatoma cells infected with mouse mammary tumor virus (MMTV) acquire viral DNA that becomes covalently linked to the cell DNA. Using restriction endonucleases and the DNA transfer procedure of Southern [Southern , E.M. (1975) J. Mol. Biol. 98, 503--517], we have studied the sites in cellular DNA into which MMTV DNA inserts. These experiments indicate that: (i) there are many sites in cell DNA into which MMTV DNA integrates; (ii) the junctions between viral and cellular DNA occur within a limited portion of the viral genome, (iii) clones that contain MMTV DNA do not necessarily produce viral RNA; and (iv) the extent of transcription and glucocorticoid responsiveness of MMTV proviruses may be dependent on the site(s) in cell DNA in which the viral DNA resides.", "contents": "Integration and transcription of mouse mammary tumor virus DNA in rat hepatoma cells. Rat hepatoma cells infected with mouse mammary tumor virus (MMTV) acquire viral DNA that becomes covalently linked to the cell DNA. Using restriction endonucleases and the DNA transfer procedure of Southern [Southern , E.M. (1975) J. Mol. Biol. 98, 503--517], we have studied the sites in cellular DNA into which MMTV DNA inserts. These experiments indicate that: (i) there are many sites in cell DNA into which MMTV DNA integrates; (ii) the junctions between viral and cellular DNA occur within a limited portion of the viral genome, (iii) clones that contain MMTV DNA do not necessarily produce viral RNA; and (iv) the extent of transcription and glucocorticoid responsiveness of MMTV proviruses may be dependent on the site(s) in cell DNA in which the viral DNA resides."}
{"id": "PMID:218216", "title": "Strand-specific attachment of avidin-spheres to double-stranded poliovirus RNA.", "content": "Poliovirus-specific double-stranded RNA molecules containing covalently attached protein were coupled with a biotin ester through the protein moiety. Subsequent interaction of the RNA-biotin with avidin attached to electronopaque plastic spheres led to the formation of complexes that were easily visualized in the electron microscope. Avidinspheres were associated only with one end of the RNA-biotin molecules, as seen in the electron microscope. Avidin-sphere attachment to poliovirus double-stranded RNA is strand specific, as shown by molecular hybridization of strand-specific probes to the separated strands of denatured complexes. [3H]DNA complementary to polio virion RNA hybridized exclusively to the strands bearing associated spheres [(+) strands] whereas 125I-labeled virion RNA hybridized predominantly with strands without spheres [(-)strands]. This biotin-avidin labeling technique provides a means for the isolation of full-length poliovirus (-) strands and may provide a general means for isolation of double-stranded polynucleotides containing tightly attached protein.", "contents": "Strand-specific attachment of avidin-spheres to double-stranded poliovirus RNA. Poliovirus-specific double-stranded RNA molecules containing covalently attached protein were coupled with a biotin ester through the protein moiety. Subsequent interaction of the RNA-biotin with avidin attached to electronopaque plastic spheres led to the formation of complexes that were easily visualized in the electron microscope. Avidinspheres were associated only with one end of the RNA-biotin molecules, as seen in the electron microscope. Avidin-sphere attachment to poliovirus double-stranded RNA is strand specific, as shown by molecular hybridization of strand-specific probes to the separated strands of denatured complexes. [3H]DNA complementary to polio virion RNA hybridized exclusively to the strands bearing associated spheres [(+) strands] whereas 125I-labeled virion RNA hybridized predominantly with strands without spheres [(-)strands]. This biotin-avidin labeling technique provides a means for the isolation of full-length poliovirus (-) strands and may provide a general means for isolation of double-stranded polynucleotides containing tightly attached protein."}
{"id": "PMID:218217", "title": "Contribution of negative cooperativity to the thyrotropin-receptor interaction in normal human thyroid: kinetic evaluation.", "content": "The kinetics of 125I-labeled thyrotropin (125I-TSH) binding to human thyroid receptors are presented. At pH 6.0, binding was maximal (30--35%) and there was one class of binding sites [Kd = 6.8 X 10(-9) M; binding capacity (Ro) = 57 pmol/mg of protein]. At pH 7.4, Scatchard plots of binding were nonlinear, indicating either a single class of negatively cooperative sites (Kd = 3.7 X 10(-9) M; Ro = 26 pmol/mg of protein) or, alternatively, independent high- (Kd = 5.0 X 10(-10) M; Ro = 3 pmol/mg of protein) and low-affinity (Kd = 1.7 X 10(-8) M; Ro = 26 pmol/mg of protein) binding sites. The role of negative cooperativity was evaluated from the rates of association and dissociation at pH 7.4. The kinetically determined binding constants (Kd = 1.7 X 10(-11) M; Ro = 2 pmol/mg of protein) were more similar to those determined for the high-affinity component than to those predicted from the negative cooperativity model. Dissociation of bound TSH was independent of initial site occupancy over a 40-fold range, corresponding to a 100-fold range of free TSH concentration. The dissociation rate of 125I-TSH was enhanced by unlabeled TSH to a similar degree, irrespective of initial binding site occupancy. Because the negative cooperativity model does not accommodate these data, it is concluded that TSH receptors in human thyroid behave kinetically and at equilibrium as a single class of high-affinity sites up to TSH concentrations well above the physiological range.", "contents": "Contribution of negative cooperativity to the thyrotropin-receptor interaction in normal human thyroid: kinetic evaluation. The kinetics of 125I-labeled thyrotropin (125I-TSH) binding to human thyroid receptors are presented. At pH 6.0, binding was maximal (30--35%) and there was one class of binding sites [Kd = 6.8 X 10(-9) M; binding capacity (Ro) = 57 pmol/mg of protein]. At pH 7.4, Scatchard plots of binding were nonlinear, indicating either a single class of negatively cooperative sites (Kd = 3.7 X 10(-9) M; Ro = 26 pmol/mg of protein) or, alternatively, independent high- (Kd = 5.0 X 10(-10) M; Ro = 3 pmol/mg of protein) and low-affinity (Kd = 1.7 X 10(-8) M; Ro = 26 pmol/mg of protein) binding sites. The role of negative cooperativity was evaluated from the rates of association and dissociation at pH 7.4. The kinetically determined binding constants (Kd = 1.7 X 10(-11) M; Ro = 2 pmol/mg of protein) were more similar to those determined for the high-affinity component than to those predicted from the negative cooperativity model. Dissociation of bound TSH was independent of initial site occupancy over a 40-fold range, corresponding to a 100-fold range of free TSH concentration. The dissociation rate of 125I-TSH was enhanced by unlabeled TSH to a similar degree, irrespective of initial binding site occupancy. Because the negative cooperativity model does not accommodate these data, it is concluded that TSH receptors in human thyroid behave kinetically and at equilibrium as a single class of high-affinity sites up to TSH concentrations well above the physiological range."}
{"id": "PMID:218218", "title": "Cyclic AMP-dependent ATPase activity of bovine heart protein kinase.", "content": "The adenosine 3\",5\"-monophosphate (cAMP)-dependent ATPase (ATP phosphohydrolase, EC 3.6.1.3) activity of cAMP-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37) from bovine heart is characterized. That the ATPase activity is intimately associated with the catalytic subunit of the enzyme is suggested by the following: (i) the similar dependences of ATPase and protein kinase activities on cAMP; (ii) the dissociation of ATPase activity from the holoenzyme on addition of cAMP and its co-elution with the catalytic subunit on gel filtration chromatography; (iii) the similarity of the relative effectiveness of divalent metal ions in ATPase and protein kinase catalysis; and (iv) the correspondence of kinetically determined Km(MgATP) and Ki(MgADP) values with thermodynamic dissociation constants determined by equilibrium dialysis. The hydrolysis of ATP is stimulated 10- to 20-fold by cAMP in the holoenzyme. The molar specific activity of the catalytic subunit ATPase is approximately 0.7 min-1 with Km(MgATP) = 5 muM. MgADP is a competitive inhibitor of the reaction with a Ki value of approximately muM. The order of the relative effectiveness of metal ions for both ATPase and peptide kinase activities is Mg2+ greater than Mn2+ greater than Ca2+. A possible interpretation of these observations is that the role that the metal ion plays is more directly manifested in bond-breaking than in bond-forming.", "contents": "Cyclic AMP-dependent ATPase activity of bovine heart protein kinase. The adenosine 3\",5\"-monophosphate (cAMP)-dependent ATPase (ATP phosphohydrolase, EC 3.6.1.3) activity of cAMP-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37) from bovine heart is characterized. That the ATPase activity is intimately associated with the catalytic subunit of the enzyme is suggested by the following: (i) the similar dependences of ATPase and protein kinase activities on cAMP; (ii) the dissociation of ATPase activity from the holoenzyme on addition of cAMP and its co-elution with the catalytic subunit on gel filtration chromatography; (iii) the similarity of the relative effectiveness of divalent metal ions in ATPase and protein kinase catalysis; and (iv) the correspondence of kinetically determined Km(MgATP) and Ki(MgADP) values with thermodynamic dissociation constants determined by equilibrium dialysis. The hydrolysis of ATP is stimulated 10- to 20-fold by cAMP in the holoenzyme. The molar specific activity of the catalytic subunit ATPase is approximately 0.7 min-1 with Km(MgATP) = 5 muM. MgADP is a competitive inhibitor of the reaction with a Ki value of approximately muM. The order of the relative effectiveness of metal ions for both ATPase and peptide kinase activities is Mg2+ greater than Mn2+ greater than Ca2+. A possible interpretation of these observations is that the role that the metal ion plays is more directly manifested in bond-breaking than in bond-forming."}
{"id": "PMID:218219", "title": "Tumor initiators and promoters in the induction of Epstein-Barr virus.", "content": "The effect of various tumor initiators and promoters on induction of persisting Epstein-Barr virus (EBV) in different lines of lymphoblastoid cells was analyzed. Neither five polycyclic aromatic hydrocarbons, amongst them potent tumor initiators (e.g., 7,12-dimethylbenz[a]anthracene), nor the potent (ultimate) liver carcinogen N-acetoxy-N-2-acetylamino-fluorene induced EBV. A series of compounds, representing three classes of tumor-promoting diterpene esters (e.g., 12-O-tetradecanoylphorbol-13-acetate), efficiently induced EBV in persistently infected cells. The concentration required for maximal induction ranged between 0.5 and 100 nM. Some nonpromoting diterpenes (phorbol, 4alpha-phorbol-12,13-didecanoate, and ingenol) did not induce EBV. However, the nonpromoters, resiniferatoxin and 12-deoxyphorbol-13-decatrienoate, were effective, whereas anthralin, a tumor promoter, did not induce EBV. In three lines of EBV genome-carrying cells (Raji, NC-37, and RPMI 64-10) only abortive induction was noted, leading exclusively to synthesis of early antigen. In cells of lines with low spontaneous virus release (P3HR-1, B95-8, and QIMR-Wil), upon treatment with tetradecanoylphorbol acetate, approximately 20-40 times more viral DNA was recovered as compared to untreated controls. Viral DNA from tetradeca-noylphorbol acetate-induced cultures revealed the same restriction endonuclease cleavage pattern as viral DNA obtained from noninduced cells. Within 10 days after induction, release of infectious virus increased approximately by one order of magnitude. Prostaglandins, reported to be released after treatment with tumor promoters, were ineffective in virus induction under the conditions tested.", "contents": "Tumor initiators and promoters in the induction of Epstein-Barr virus. The effect of various tumor initiators and promoters on induction of persisting Epstein-Barr virus (EBV) in different lines of lymphoblastoid cells was analyzed. Neither five polycyclic aromatic hydrocarbons, amongst them potent tumor initiators (e.g., 7,12-dimethylbenz[a]anthracene), nor the potent (ultimate) liver carcinogen N-acetoxy-N-2-acetylamino-fluorene induced EBV. A series of compounds, representing three classes of tumor-promoting diterpene esters (e.g., 12-O-tetradecanoylphorbol-13-acetate), efficiently induced EBV in persistently infected cells. The concentration required for maximal induction ranged between 0.5 and 100 nM. Some nonpromoting diterpenes (phorbol, 4alpha-phorbol-12,13-didecanoate, and ingenol) did not induce EBV. However, the nonpromoters, resiniferatoxin and 12-deoxyphorbol-13-decatrienoate, were effective, whereas anthralin, a tumor promoter, did not induce EBV. In three lines of EBV genome-carrying cells (Raji, NC-37, and RPMI 64-10) only abortive induction was noted, leading exclusively to synthesis of early antigen. In cells of lines with low spontaneous virus release (P3HR-1, B95-8, and QIMR-Wil), upon treatment with tetradecanoylphorbol acetate, approximately 20-40 times more viral DNA was recovered as compared to untreated controls. Viral DNA from tetradeca-noylphorbol acetate-induced cultures revealed the same restriction endonuclease cleavage pattern as viral DNA obtained from noninduced cells. Within 10 days after induction, release of infectious virus increased approximately by one order of magnitude. Prostaglandins, reported to be released after treatment with tumor promoters, were ineffective in virus induction under the conditions tested."}
{"id": "PMID:218220", "title": "Evidence for role of glycoprotein carbohydrates in membrane transport: specific inhibition by tunicamycin.", "content": "Using tunicamycin, we have investigated the role of glycoproteins in membrane transport. Tunicamycin is a glucosamine-containing antibiotic that specifically inhibits dolichol pyrophosphate-mediated glycosylation of asparaginyl residues of glycoproteins. Inhibition of protein glycosylation in chick embryo fibroblasts by tunicamycin or other inhibitors of glycosylation resulted in defective transport of glucose, uridine, and amino acid analogs (alpha-aminoisobutyrate and cycloleucine). The defect in glucose transport is accompanied by decreased glucose metabolism, as determined by rates of CO2 and lactate production. In contrast, tunicamycin treatment did not affect other membrane-associated processes, such as secretion of fibronectin and procollagen, uptake of glucose by passive diffusion, Na+/K+ ATPase and adenylate cyclase activities, or stimulation of adenylate cyclase by prostaglandin and cholera toxin. Two glucose/glycosylation-regulated membrane proteins with apparent subunit molecular weights of 95,000 and 75,000 were induced by tunicamycin treatment. Our results indicate that glycoprotein glycosylation is required for membrane transport.", "contents": "Evidence for role of glycoprotein carbohydrates in membrane transport: specific inhibition by tunicamycin. Using tunicamycin, we have investigated the role of glycoproteins in membrane transport. Tunicamycin is a glucosamine-containing antibiotic that specifically inhibits dolichol pyrophosphate-mediated glycosylation of asparaginyl residues of glycoproteins. Inhibition of protein glycosylation in chick embryo fibroblasts by tunicamycin or other inhibitors of glycosylation resulted in defective transport of glucose, uridine, and amino acid analogs (alpha-aminoisobutyrate and cycloleucine). The defect in glucose transport is accompanied by decreased glucose metabolism, as determined by rates of CO2 and lactate production. In contrast, tunicamycin treatment did not affect other membrane-associated processes, such as secretion of fibronectin and procollagen, uptake of glucose by passive diffusion, Na+/K+ ATPase and adenylate cyclase activities, or stimulation of adenylate cyclase by prostaglandin and cholera toxin. Two glucose/glycosylation-regulated membrane proteins with apparent subunit molecular weights of 95,000 and 75,000 were induced by tunicamycin treatment. Our results indicate that glycoprotein glycosylation is required for membrane transport."}
{"id": "PMID:218221", "title": "Immunological evidence for two common precursors to corticotropins, endorphins, and melanotropin in the neurointermediate lobe of the toad pituitary.", "content": "The biosynthesis of corticotropin (ACTH1--39), beta-endorphin [beta(61--91)-lipotropin] and alpha-melanotropin in the toad intermediate lobe was studied by using immunoprecipitation procedures with antisera specific for these peptides. Intermediate lobes were pulse-incubated with [3H]phenylalanine and then chase-incubated for varying periods; the radioactive proteins were immunoprecipitated. Immunoprecipitates were separated by acidic urea or sodium dodecyl sulfate polyacrylamide gel electrophoresis. Evidence from the pulse-chase and sequential immunoprecipitation studies using antisera to ACTH and beta-endorphin suggests that the toad intermediate lobe synthesizes two common precursors (apparent Mr 32,000 and 29,500) containing both the ACTH and beta-endorphin sequences. These precursors are processed to yield several forms of immunoreactive corticotropin (apparent Mr 23,000, 21,000, 13,000, and 4300), immunoreactive endorphin (apparent Mr 11,700 and 3500), and immunoreactive alpha-melanotropin. The 4300 Mr form of corticotropin and the 11,700 and 3500 Mr forms of endorphins were found to comigrate with synthetic ACTH1--39, beta-lipotropin and beta-endorphin, respectively, on both acidic urea and sodium dodecyl sulfate gels.", "contents": "Immunological evidence for two common precursors to corticotropins, endorphins, and melanotropin in the neurointermediate lobe of the toad pituitary. The biosynthesis of corticotropin (ACTH1--39), beta-endorphin [beta(61--91)-lipotropin] and alpha-melanotropin in the toad intermediate lobe was studied by using immunoprecipitation procedures with antisera specific for these peptides. Intermediate lobes were pulse-incubated with [3H]phenylalanine and then chase-incubated for varying periods; the radioactive proteins were immunoprecipitated. Immunoprecipitates were separated by acidic urea or sodium dodecyl sulfate polyacrylamide gel electrophoresis. Evidence from the pulse-chase and sequential immunoprecipitation studies using antisera to ACTH and beta-endorphin suggests that the toad intermediate lobe synthesizes two common precursors (apparent Mr 32,000 and 29,500) containing both the ACTH and beta-endorphin sequences. These precursors are processed to yield several forms of immunoreactive corticotropin (apparent Mr 23,000, 21,000, 13,000, and 4300), immunoreactive endorphin (apparent Mr 11,700 and 3500), and immunoreactive alpha-melanotropin. The 4300 Mr form of corticotropin and the 11,700 and 3500 Mr forms of endorphins were found to comigrate with synthetic ACTH1--39, beta-lipotropin and beta-endorphin, respectively, on both acidic urea and sodium dodecyl sulfate gels."}
{"id": "PMID:218222", "title": "Altered pattern of growth and differentiation in human keratinocytes infected by simian virus 40.", "content": "Human epidermal keratinocytes were infected by simian virus 40 in vitro. The structure of the developing keratinocyte colony reflects the spatial separation of cell division and keratinization in intact skin; thymidine-incorporating cells were primarily localized at the colony periphery whereas nondividing, histologically differentiated cells accumulated in the interior. Viral infection produced a dramatic increase in the size of the proliferative population as, simultaneously, differentiation was reduced in the colony interior. These changes were manifest when simian virus 40 T-antigen synthesis was detectable in only a small percentage of the cells; differentiation became increasingly density dependent as the percentage of T-antigen-positive cells rose over serial passage. The disruption of the normal pattern of growth/differentiation localization coincided with a loss of dependence on serum for growth, but preceded the appearance of other virus-induced properties associated with transformation; i.e., the ability to form colonies in soft agar and independence of growth from fibroblasts.", "contents": "Altered pattern of growth and differentiation in human keratinocytes infected by simian virus 40. Human epidermal keratinocytes were infected by simian virus 40 in vitro. The structure of the developing keratinocyte colony reflects the spatial separation of cell division and keratinization in intact skin; thymidine-incorporating cells were primarily localized at the colony periphery whereas nondividing, histologically differentiated cells accumulated in the interior. Viral infection produced a dramatic increase in the size of the proliferative population as, simultaneously, differentiation was reduced in the colony interior. These changes were manifest when simian virus 40 T-antigen synthesis was detectable in only a small percentage of the cells; differentiation became increasingly density dependent as the percentage of T-antigen-positive cells rose over serial passage. The disruption of the normal pattern of growth/differentiation localization coincided with a loss of dependence on serum for growth, but preceded the appearance of other virus-induced properties associated with transformation; i.e., the ability to form colonies in soft agar and independence of growth from fibroblasts."}
{"id": "PMID:218223", "title": "Triene prostaglandins: prostacyclin and thromboxane biosynthesis and unique biological properties.", "content": "Platelets enzymatically convert prostaglandin H(3) (PGH(3)) into thromboxane A(3). Both PGH(2) and thromboxane A(2) aggregate human platelet-rich plasma. In contrast, PGH(3) and thromboxane A(3) do not. PGH(3) and thromboxane A(3) increase platelet cyclic AMP in platelet-rich plasma and thereby: (i) inhibit aggregation by other agonists, (ii) block the ADP-induced release reaction, and (iii) suppress platelet phospholipase-A(2) activity or events leading to its activation. PGI(3) (Delta(17)-prostacyclin; synthesized from PGH(3) by blood vessel enzyme) and PGI(2) (prostacyclin) exert similar effects. Both compounds are potent coronary relaxants that also inhibit aggregation in human platelet-rich plasma and increase platelet adenylate cyclase activity. Radioactive eicosapentaenoate and arachidonate are readily and comparably acylated into platelet phospholipids. In addition, stimulation of prelabeled platelets with thrombin releases comparable amounts of eicosapentaenoate and arachidonate, respectively. Although eicosapentaenoic acid is a relatively poor substrate for platelet cyclooxygenase, it appears to have a high binding affinity and thereby inhibits arachidonic acid conversion by platelet cyclooxygenase and lipoxygenase. It is therefore possible that the triene prostaglandins are potential antithrombotic agents because their precursor fatty acids, as well as their transformation products, PGH(3), thromboxane A(3), and PGI(3), are capable of interfering with aggregation of platelets in platelet-rich plasma.", "contents": "Triene prostaglandins: prostacyclin and thromboxane biosynthesis and unique biological properties. Platelets enzymatically convert prostaglandin H(3) (PGH(3)) into thromboxane A(3). Both PGH(2) and thromboxane A(2) aggregate human platelet-rich plasma. In contrast, PGH(3) and thromboxane A(3) do not. PGH(3) and thromboxane A(3) increase platelet cyclic AMP in platelet-rich plasma and thereby: (i) inhibit aggregation by other agonists, (ii) block the ADP-induced release reaction, and (iii) suppress platelet phospholipase-A(2) activity or events leading to its activation. PGI(3) (Delta(17)-prostacyclin; synthesized from PGH(3) by blood vessel enzyme) and PGI(2) (prostacyclin) exert similar effects. Both compounds are potent coronary relaxants that also inhibit aggregation in human platelet-rich plasma and increase platelet adenylate cyclase activity. Radioactive eicosapentaenoate and arachidonate are readily and comparably acylated into platelet phospholipids. In addition, stimulation of prelabeled platelets with thrombin releases comparable amounts of eicosapentaenoate and arachidonate, respectively. Although eicosapentaenoic acid is a relatively poor substrate for platelet cyclooxygenase, it appears to have a high binding affinity and thereby inhibits arachidonic acid conversion by platelet cyclooxygenase and lipoxygenase. It is therefore possible that the triene prostaglandins are potential antithrombotic agents because their precursor fatty acids, as well as their transformation products, PGH(3), thromboxane A(3), and PGI(3), are capable of interfering with aggregation of platelets in platelet-rich plasma."}
{"id": "PMID:218224", "title": "Transfection of human lymphoblastoid cells with herpes simplex viral DNA.", "content": "The \"calcium/dimethyl sulfoxide shock\" method of transfection was adapted for use in human lymphoid cell cultures. One microgram of herpes simplex virus type 1 DNA regularly initiated virus replication in four lymphoblastoid cell lines. Per 10(5) cells exposed to 1 microgram of DNA, 0.5--5 cells formed an infectious center. The minimal infective dose of DNA was approximately 500 ng.", "contents": "Transfection of human lymphoblastoid cells with herpes simplex viral DNA. The \"calcium/dimethyl sulfoxide shock\" method of transfection was adapted for use in human lymphoid cell cultures. One microgram of herpes simplex virus type 1 DNA regularly initiated virus replication in four lymphoblastoid cell lines. Per 10(5) cells exposed to 1 microgram of DNA, 0.5--5 cells formed an infectious center. The minimal infective dose of DNA was approximately 500 ng."}
{"id": "PMID:218225", "title": "Src Gene product from different strains of avian sarcoma virus: Kinetics and possible mechanism of heat inactivation of protein kinase activity from cells infected by transformation-defective, temperature-sensitive mutant and wild-type virus.", "content": "Sera from certain rabbits bearing Schmidt-Ruppin strain Rous sarcoma virus (RSV)-induced tumors precipitated p60(src) from chicken cells transformed by the homologous virus as well as by other strains [Prague strain RSV, Bryan high-titer strain RSV, and Bratislava 77 strain of avain sarcoma virus (ASV)], the molecular weights (M(r)s) ranging from 60,000 to 64,000. The p60(src) immunoprecipitated from cells transformed by each of these strains incorporated [gamma-(32)P]ATP into the M(r) 53,000 subunit of IgG, though with differing activities. No such protein kinase activity (ATP:protein phosphotransferase, EC 2.7.1.37) was observed when the following immunoprecipitates were used: from uninfected cells, from untransformed cells infected by Rous-associated virus, or from cells transformed by acute leukosis viruses, avian erythroblastosis virus, or myelocytoma virus 29. The kinase reaction had a pH optimum at pH 5.9 and an apparent K(m) for ATP of 4.9 +/- 2 muM, and was dependent on Mg(2+) (K(b) = 46 +/- 12 mM), for which Ca(2+) was no substitute. The kinase was cyclic AMP independent. In order to test whether the protein kinase reaction is directly catalyzed by p60(src), we compared the in vitro temperature sensitivities of the kinase activities from cells infected by transformation-temperature-sensitive mutant and parental wild-type virus. The first-order rate constant for the inactivation of the kinase from extracts of cells infected by the mutant virus was 2-fold greater than that from cells infected by wild-type virus. This result implicates the protein kinase as an enzymatic activity of the src gene product, the p60(src). Concomitant with the loss of the kinase activity by heat inactivation, p60(src) loses 60-70% of its phosphate content. The kinetics of dephosphorylation exactly parallel those for the inactivation of the kinase activity, suggesting that the p60(src) kinase is itself dependent on phosphorylation for its activity.", "contents": "Src Gene product from different strains of avian sarcoma virus: Kinetics and possible mechanism of heat inactivation of protein kinase activity from cells infected by transformation-defective, temperature-sensitive mutant and wild-type virus. Sera from certain rabbits bearing Schmidt-Ruppin strain Rous sarcoma virus (RSV)-induced tumors precipitated p60(src) from chicken cells transformed by the homologous virus as well as by other strains [Prague strain RSV, Bryan high-titer strain RSV, and Bratislava 77 strain of avain sarcoma virus (ASV)], the molecular weights (M(r)s) ranging from 60,000 to 64,000. The p60(src) immunoprecipitated from cells transformed by each of these strains incorporated [gamma-(32)P]ATP into the M(r) 53,000 subunit of IgG, though with differing activities. No such protein kinase activity (ATP:protein phosphotransferase, EC 2.7.1.37) was observed when the following immunoprecipitates were used: from uninfected cells, from untransformed cells infected by Rous-associated virus, or from cells transformed by acute leukosis viruses, avian erythroblastosis virus, or myelocytoma virus 29. The kinase reaction had a pH optimum at pH 5.9 and an apparent K(m) for ATP of 4.9 +/- 2 muM, and was dependent on Mg(2+) (K(b) = 46 +/- 12 mM), for which Ca(2+) was no substitute. The kinase was cyclic AMP independent. In order to test whether the protein kinase reaction is directly catalyzed by p60(src), we compared the in vitro temperature sensitivities of the kinase activities from cells infected by transformation-temperature-sensitive mutant and parental wild-type virus. The first-order rate constant for the inactivation of the kinase from extracts of cells infected by the mutant virus was 2-fold greater than that from cells infected by wild-type virus. This result implicates the protein kinase as an enzymatic activity of the src gene product, the p60(src). Concomitant with the loss of the kinase activity by heat inactivation, p60(src) loses 60-70% of its phosphate content. The kinetics of dephosphorylation exactly parallel those for the inactivation of the kinase activity, suggesting that the p60(src) kinase is itself dependent on phosphorylation for its activity."}
{"id": "PMID:218235", "title": "Effects of chronic parenteral carbohydrate administration on hepatic drug metabolism in the rat.", "content": "Effects of chronic parenteral carbohydrate administration on hepatic microsomal enzyme activity were studied in the rat. Intraperitoneal injections of either glucose or fructose (2.88 g daily for 7 days) significantly decreased hepatic cytochrome P-450 content and ethylmorphine N-demethylase and aniline hydroxylase activities. By the 5th day, cytochrome P-450 content decreased to 70-76% and ethylmorphine N-demethylase activity to 66-69% of control values. Aniline hydroxylase activity was not significantly altered until the 7th day, by which time it was 77-79% of control values. In vivo assessment of hepatic drug-metabolizing capacity using antipyrine as a test drug confirmed these decreases observed in vitro. Two major conclusions of these experiments are that such variables as time and dose of carbohydrate administration can affect the magnitude of the changes produced and that each parameter measured exhibited a distinctive pattern of change with time. Chronic carbohydrate administration produced hepatic fatty infiltration and glycogen depletion. Since all groups received identical amounts of specific nutrients, fatty infiltration was probably due to increased lipogenesis with decreased hepatic oxidative metabolism of fat. During these experiments neither hypoinsulinemia nor increased levels of cyclic AMP were observed. The molecular mechanisms responsible for hepatic glycogen depletion and decreased MFO activities remain to be established.", "contents": "Effects of chronic parenteral carbohydrate administration on hepatic drug metabolism in the rat. Effects of chronic parenteral carbohydrate administration on hepatic microsomal enzyme activity were studied in the rat. Intraperitoneal injections of either glucose or fructose (2.88 g daily for 7 days) significantly decreased hepatic cytochrome P-450 content and ethylmorphine N-demethylase and aniline hydroxylase activities. By the 5th day, cytochrome P-450 content decreased to 70-76% and ethylmorphine N-demethylase activity to 66-69% of control values. Aniline hydroxylase activity was not significantly altered until the 7th day, by which time it was 77-79% of control values. In vivo assessment of hepatic drug-metabolizing capacity using antipyrine as a test drug confirmed these decreases observed in vitro. Two major conclusions of these experiments are that such variables as time and dose of carbohydrate administration can affect the magnitude of the changes produced and that each parameter measured exhibited a distinctive pattern of change with time. Chronic carbohydrate administration produced hepatic fatty infiltration and glycogen depletion. Since all groups received identical amounts of specific nutrients, fatty infiltration was probably due to increased lipogenesis with decreased hepatic oxidative metabolism of fat. During these experiments neither hypoinsulinemia nor increased levels of cyclic AMP were observed. The molecular mechanisms responsible for hepatic glycogen depletion and decreased MFO activities remain to be established."}
{"id": "PMID:218237", "title": "Investigation of the mechanism of decreased sensitivity of the rat seminal vesicle to norepinephrine by lithium.", "content": "Li+ is reported to reduce sensitivity of alpha-adrenergic receptors to NE. The present investigation was designed to investigate the mechanism of this decreased sensitivity on the rat isolated seminal vesicle. In innervated preparations, 1.35 X 10(-3) M Li+ (i) shifted the concentration-response curves of NE, methoxamine, ACh and BaCl2 to the right and reduced their maximum responses; (ii) antagonized the leftward shift and the enhancement of maximum responses to NE by cocaine (2.9 X 10(-4) M), and (iii) reduced only the maximum responses to KCl. In denervated preparations, 1.35 X 10 (-3) M Li+ shifted the concentration response curve of NE to the left without any change in the maximum responses. The antagonistic effects of Li+ on maximal responses to NE, ACh and KCl observed in innervated preparations were significantly increased in Ca++-free medium. Li+ (1.35 X 10(-3) M) increased NE uptake by the seminal vesicle significantly. It is concluded that decreased sensitivity of the seminal vesicle to NE by Li+ could be due to an increase in the uptake of NE and to a nonspecific postsynaptic spasmolytic action.", "contents": "Investigation of the mechanism of decreased sensitivity of the rat seminal vesicle to norepinephrine by lithium. Li+ is reported to reduce sensitivity of alpha-adrenergic receptors to NE. The present investigation was designed to investigate the mechanism of this decreased sensitivity on the rat isolated seminal vesicle. In innervated preparations, 1.35 X 10(-3) M Li+ (i) shifted the concentration-response curves of NE, methoxamine, ACh and BaCl2 to the right and reduced their maximum responses; (ii) antagonized the leftward shift and the enhancement of maximum responses to NE by cocaine (2.9 X 10(-4) M), and (iii) reduced only the maximum responses to KCl. In denervated preparations, 1.35 X 10 (-3) M Li+ shifted the concentration response curve of NE to the left without any change in the maximum responses. The antagonistic effects of Li+ on maximal responses to NE, ACh and KCl observed in innervated preparations were significantly increased in Ca++-free medium. Li+ (1.35 X 10(-3) M) increased NE uptake by the seminal vesicle significantly. It is concluded that decreased sensitivity of the seminal vesicle to NE by Li+ could be due to an increase in the uptake of NE and to a nonspecific postsynaptic spasmolytic action."}
{"id": "PMID:218239", "title": "Use of dermal grafts to cover implants in breast reconstructions.", "content": "The use of dermal grafts for the reinforcement of the cover over implants in breast reconstructions after radical mastectomy is illustrated in several cases. By carefully selecting the patients, we feel that this relatively minor procedure may replace the use of local of distant flaps in a good many breast reconstructions.", "contents": "Use of dermal grafts to cover implants in breast reconstructions. The use of dermal grafts for the reinforcement of the cover over implants in breast reconstructions after radical mastectomy is illustrated in several cases. By carefully selecting the patients, we feel that this relatively minor procedure may replace the use of local of distant flaps in a good many breast reconstructions."}
{"id": "PMID:218240", "title": "Imipramine and EEG sleep in children with depressive symptoms.", "content": "Depression in children is currently an area of considerable controversy, as is the use of potent psychopharmacologic agents in children. Since EEG sleep techniques have proven to be useful in understanding the mechanisms of depression in adults and in predicting their response to antidepressants, a pilot study employing these techniques was undertaken in a population of hospitalized children. The EEG sleep of 12 children with significant depressive symptomatology was first examined after a two-week drug-free period and again approximately three weeks later when an optimum dose of imipramine had been maintained for at least 7 -- 10 days. Changes in sleep continuity, as reflected in increased wakefulness and a decreased sleep efficiency, as well as an increase in Stage 2 and a decrease in Stage 4 sleep, were observed throughout the entire sample. REM suppression was also noted, but tended to be most pronounced in those children who improved on imipramine.", "contents": "Imipramine and EEG sleep in children with depressive symptoms. Depression in children is currently an area of considerable controversy, as is the use of potent psychopharmacologic agents in children. Since EEG sleep techniques have proven to be useful in understanding the mechanisms of depression in adults and in predicting their response to antidepressants, a pilot study employing these techniques was undertaken in a population of hospitalized children. The EEG sleep of 12 children with significant depressive symptomatology was first examined after a two-week drug-free period and again approximately three weeks later when an optimum dose of imipramine had been maintained for at least 7 -- 10 days. Changes in sleep continuity, as reflected in increased wakefulness and a decreased sleep efficiency, as well as an increase in Stage 2 and a decrease in Stage 4 sleep, were observed throughout the entire sample. REM suppression was also noted, but tended to be most pronounced in those children who improved on imipramine."}
{"id": "PMID:218242", "title": "Computed tomographic arteriography of the liver.", "content": "Computed tomographic arteriography (CTA) of the liver performed during intra-arterial infusion of contrast material improved the detection of hepatic lesions in 10 of 12 patients and was the only method that accurately determined the extent of disease in 6. This technique has significant advantages over conventional hepatic computed tomography with or without intravenous contrast enhancement, or selective hepatic angiography. It is recommended in the evaluation of selected patients, especially when there is a discrepancy between the findings obtained by other methods.", "contents": "Computed tomographic arteriography of the liver. Computed tomographic arteriography (CTA) of the liver performed during intra-arterial infusion of contrast material improved the detection of hepatic lesions in 10 of 12 patients and was the only method that accurately determined the extent of disease in 6. This technique has significant advantages over conventional hepatic computed tomography with or without intravenous contrast enhancement, or selective hepatic angiography. It is recommended in the evaluation of selected patients, especially when there is a discrepancy between the findings obtained by other methods."}
{"id": "PMID:218243", "title": "Aberrant jugular bulb presenting as a middle ear mass.", "content": "Case reports of 3 patients seen with a bluish mass behind the tympanic membrane are presented. The initial diagnosis was probable glomus tumor. In 1 patient, middle ear exploration confirmed the presence of a high-lying jugular bulb. In the other 2, venography demonstrated that the jugular bulb projected superiorly into the middle ear cavity. In all 3, polytomography demonstrated a dehiscence of the bony septum which normally separates the jugular bulb from the hypotympanum. When a bony dehiscence is seen in the absence of destructive changes, a diagnosis of aberrant jugular bulb is strongly suggested.", "contents": "Aberrant jugular bulb presenting as a middle ear mass. Case reports of 3 patients seen with a bluish mass behind the tympanic membrane are presented. The initial diagnosis was probable glomus tumor. In 1 patient, middle ear exploration confirmed the presence of a high-lying jugular bulb. In the other 2, venography demonstrated that the jugular bulb projected superiorly into the middle ear cavity. In all 3, polytomography demonstrated a dehiscence of the bony septum which normally separates the jugular bulb from the hypotympanum. When a bony dehiscence is seen in the absence of destructive changes, a diagnosis of aberrant jugular bulb is strongly suggested."}
{"id": "PMID:218244", "title": "Computed tomography in the evaluation of hepatocellular carcinoma.", "content": "Computed tomography (CT) was used to evaluate 47 cases of hepatocellular carcinoma: it was definite in 37, equivocal in 5 and negative in 5 cases. No specific patterns of CT images were recognized. Pre- and postcontrast scans were necessary because several tumors could only be detected on one or the other scan. CT may reveal the exact extent of tumor and show additional tumors in case of multiple lesions. However, false negative results are possible in isodense or very small tumors.", "contents": "Computed tomography in the evaluation of hepatocellular carcinoma. Computed tomography (CT) was used to evaluate 47 cases of hepatocellular carcinoma: it was definite in 37, equivocal in 5 and negative in 5 cases. No specific patterns of CT images were recognized. Pre- and postcontrast scans were necessary because several tumors could only be detected on one or the other scan. CT may reveal the exact extent of tumor and show additional tumors in case of multiple lesions. However, false negative results are possible in isodense or very small tumors."}
{"id": "PMID:218245", "title": "Transcatheter occlusion of the gastroduodenal artery.", "content": "The gastroduodenal arteries of 7 patients were occluded for treatment of duodenal bleeding in 4, hepatic devascularization in 2, and redistribution of blood flow for intra-arterial chemotherapy in one patient. In 6 patients, occlusion was performed with Gianturco coils, and with Gelfoam in one. No major complication was encountered. This approach was successful in the control of bleeding from peptic ulcers, arteriovenous malformation and invasion of duodenum by retroperitoneal metastatic lymph nodes from carcinoma of the testicle. Occlusion of the gastroduodenal artery was utilized for further dearterialization of hepatic neoplasms. Redistribution of hepatic blood flow was accomplished by the occlusion of the gastroduodenal and replaced right hepatic arteries allowing infusion of chemotherapeutic agents into the entire liver through the left hepatic artery.", "contents": "Transcatheter occlusion of the gastroduodenal artery. The gastroduodenal arteries of 7 patients were occluded for treatment of duodenal bleeding in 4, hepatic devascularization in 2, and redistribution of blood flow for intra-arterial chemotherapy in one patient. In 6 patients, occlusion was performed with Gianturco coils, and with Gelfoam in one. No major complication was encountered. This approach was successful in the control of bleeding from peptic ulcers, arteriovenous malformation and invasion of duodenum by retroperitoneal metastatic lymph nodes from carcinoma of the testicle. Occlusion of the gastroduodenal artery was utilized for further dearterialization of hepatic neoplasms. Redistribution of hepatic blood flow was accomplished by the occlusion of the gastroduodenal and replaced right hepatic arteries allowing infusion of chemotherapeutic agents into the entire liver through the left hepatic artery."}
{"id": "PMID:218246", "title": "Angiography of malignant fibrous histiocytoma of bone.", "content": "Angiograms of 10 cases of malignant fibrous histiocytoma of bone were reviewed and correlated with surgical and pathological findings. Nine tumors were hypervascular. Seven demonstrated malignant characteristics (laking in one and coarse tumor vessels in 6). Seven tumors displaced adjacent normal vessels. All angiograms accurately delineated soft-tissue masses and cortical breakthrough but intraosseous extent was less clearly defined. Tumor thrombi within draining veins were evident retrospectively in one instance. Angiography in these cases contributed substantially to surgical management.", "contents": "Angiography of malignant fibrous histiocytoma of bone. Angiograms of 10 cases of malignant fibrous histiocytoma of bone were reviewed and correlated with surgical and pathological findings. Nine tumors were hypervascular. Seven demonstrated malignant characteristics (laking in one and coarse tumor vessels in 6). Seven tumors displaced adjacent normal vessels. All angiograms accurately delineated soft-tissue masses and cortical breakthrough but intraosseous extent was less clearly defined. Tumor thrombi within draining veins were evident retrospectively in one instance. Angiography in these cases contributed substantially to surgical management."}
{"id": "PMID:218255", "title": "[The radiological symptomatology of primary malignant neoplasia of the kidney (author's transl)].", "content": "The radiological signs characteristic of various forms of renal neoplasia are described and the diagnostic value of different radiological techniques is discussed. A rational procedure for the study of primary tumours of the renal parenchyma is proposed, and several cases are presented by way of illustration.", "contents": "[The radiological symptomatology of primary malignant neoplasia of the kidney (author's transl)]. The radiological signs characteristic of various forms of renal neoplasia are described and the diagnostic value of different radiological techniques is discussed. A rational procedure for the study of primary tumours of the renal parenchyma is proposed, and several cases are presented by way of illustration."}
{"id": "PMID:218258", "title": "[Cancer epidemiology and French medical data (author's transl)].", "content": "The authors remind: cancerous disease's possibilities of description before any treatment through its topography, its morphology and its clinical medicine; the modalities for taking surgical, actinic, chemical, immunologic therapeutics in account; the technics of the cancerous disease supervision after treatment, from the vital points of view (study of observed and relative survival, and of recovery) and from the carcinologic and fonctionnal points of view. They insist on the possibilities of these languages that go from the simple notation of information to the taking of these sundries modalities in account. The disposable datums in France are schematicly described. They concern: the study of survival from hospitable series; mortality by cancer for the whole of the country. The authors consider that no entry must be undertaken without the purposes, in the same way as the considered modalities for analysis, being precisely fixed. They insist on the notion of information level, of which three levels are schematicly defined, according as descriptive epidemiology or epidemiologic research or clinical research is in question.", "contents": "[Cancer epidemiology and French medical data (author's transl)]. The authors remind: cancerous disease's possibilities of description before any treatment through its topography, its morphology and its clinical medicine; the modalities for taking surgical, actinic, chemical, immunologic therapeutics in account; the technics of the cancerous disease supervision after treatment, from the vital points of view (study of observed and relative survival, and of recovery) and from the carcinologic and fonctionnal points of view. They insist on the possibilities of these languages that go from the simple notation of information to the taking of these sundries modalities in account. The disposable datums in France are schematicly described. They concern: the study of survival from hospitable series; mortality by cancer for the whole of the country. The authors consider that no entry must be undertaken without the purposes, in the same way as the considered modalities for analysis, being precisely fixed. They insist on the notion of information level, of which three levels are schematicly defined, according as descriptive epidemiology or epidemiologic research or clinical research is in question."}
{"id": "PMID:218259", "title": "[Modern methods for surveillance of communicable disease: general introduction (author's transl)].", "content": "Epidemiological surveillance has now become a fully developed discipline, to which several technical specialties contribute. All kinds of new problems resulting from present conditions of life have enlarged the field of surveillance beyond the old concept of morbidity-mortality. This has necessitated the application of new methodology--a stimulating challenge for those who are engaged in epidemiological surveillance.", "contents": "[Modern methods for surveillance of communicable disease: general introduction (author's transl)]. Epidemiological surveillance has now become a fully developed discipline, to which several technical specialties contribute. All kinds of new problems resulting from present conditions of life have enlarged the field of surveillance beyond the old concept of morbidity-mortality. This has necessitated the application of new methodology--a stimulating challenge for those who are engaged in epidemiological surveillance."}
{"id": "PMID:218260", "title": "[International influenza surveillance (author's transl)].", "content": "Influenza may be considered a convenient model to set up a methodology for surveillance in a country, which can further be extended to other diseases. The solidarity which exists among Directors of National Influenza Centres is one of the reasons for its success. On positive result, and one which is not negligible, has been the stimulating effect which influenza surveillance had on the development of virus laboratories in tropical regions.", "contents": "[International influenza surveillance (author's transl)]. Influenza may be considered a convenient model to set up a methodology for surveillance in a country, which can further be extended to other diseases. The solidarity which exists among Directors of National Influenza Centres is one of the reasons for its success. On positive result, and one which is not negligible, has been the stimulating effect which influenza surveillance had on the development of virus laboratories in tropical regions."}
{"id": "PMID:218261", "title": "[Network for the epidemiological survey of the enteroviruses in sewage (author's transl)].", "content": "Poliomyelitis still occurs each year in France: 27 cases in 1973, 21 cases in each of 1974 and 1975, 8 cases in 1976. Because of the risk, a survey of the spread of poliovirus in healthy populations and in sewage was organized by the Ministry of Health according to the departmental note DGS/HP/1st/250, 9-2-73. The Laboratoire d'Epid\u00e9miologie Virale of the Laboratoire National de la Sant\u00e9 was in charge of the technical aspects of the survey. A preliminary questionnaire was sent to each D.D.A.S.S. (Direction D\u00e9partementale de l'Action Sanitaire et Sociale) in order to find out the local possibilities for sampling and preliminary treatment of the sewage samples. In 1974, all the samples were sent to the Laboratoire d'Epid\u00e9miologie Virale. Since 1975, samples have been sent to a local virology laboratory when available. The sewage samples were concentrated according to SHUVAL's or LUND's methods depending on the local conditions. Both methods tested in our laboratory were found equally efficient. In order to improve their technical laboratory methods, the virologists collaborating in this survey joined together in a working group \"Virus et Eaux\". For isolating the enteroviruses, we recommend the inoculation of each concentrated sample into primary monkey kidney cells grown in vials; an overlay of agar is added after inoculation. This plaque method allowed us to isolate several strains from one sample. It was possible to demonstrate that polioviruses differing in serotypes and thermosensitivity might be detectable in the same sample. Few of the isolated polioviruses (11/272) showed the same thermoresistance as did the wild strains. Certain enterovirus serotypes are known to be responsible for epidemics of meningitis and neurological disorders. It was of interest to identify non-poliomyelitic enteroviruses isolated from sewage. The study of enterovirus spread in sewage in comparison with that in healthy children is in progress.", "contents": "[Network for the epidemiological survey of the enteroviruses in sewage (author's transl)]. Poliomyelitis still occurs each year in France: 27 cases in 1973, 21 cases in each of 1974 and 1975, 8 cases in 1976. Because of the risk, a survey of the spread of poliovirus in healthy populations and in sewage was organized by the Ministry of Health according to the departmental note DGS/HP/1st/250, 9-2-73. The Laboratoire d'Epid\u00e9miologie Virale of the Laboratoire National de la Sant\u00e9 was in charge of the technical aspects of the survey. A preliminary questionnaire was sent to each D.D.A.S.S. (Direction D\u00e9partementale de l'Action Sanitaire et Sociale) in order to find out the local possibilities for sampling and preliminary treatment of the sewage samples. In 1974, all the samples were sent to the Laboratoire d'Epid\u00e9miologie Virale. Since 1975, samples have been sent to a local virology laboratory when available. The sewage samples were concentrated according to SHUVAL's or LUND's methods depending on the local conditions. Both methods tested in our laboratory were found equally efficient. In order to improve their technical laboratory methods, the virologists collaborating in this survey joined together in a working group \"Virus et Eaux\". For isolating the enteroviruses, we recommend the inoculation of each concentrated sample into primary monkey kidney cells grown in vials; an overlay of agar is added after inoculation. This plaque method allowed us to isolate several strains from one sample. It was possible to demonstrate that polioviruses differing in serotypes and thermosensitivity might be detectable in the same sample. Few of the isolated polioviruses (11/272) showed the same thermoresistance as did the wild strains. Certain enterovirus serotypes are known to be responsible for epidemics of meningitis and neurological disorders. It was of interest to identify non-poliomyelitic enteroviruses isolated from sewage. The study of enterovirus spread in sewage in comparison with that in healthy children is in progress."}
{"id": "PMID:218263", "title": "[Experimental investigations of the content of glycogen in the adrenal gland of the rat after application of dexamethasone, ACTH and a combination of both (author's transl)].", "content": "The influence of dexamethasone, ACTH and the combination of both on the glycogen content of the rat adrenal gland was studied. Dexamethasone induces a transient increase of the adrenal glycogen content in a time and dose-dependent manner. The application of ACTH has no effect on the glycogen content. Surprisingly, the increase of the glycogen content induced by dexamethasone is completely blocked by the simultaneous application of ACTH.", "contents": "[Experimental investigations of the content of glycogen in the adrenal gland of the rat after application of dexamethasone, ACTH and a combination of both (author's transl)]. The influence of dexamethasone, ACTH and the combination of both on the glycogen content of the rat adrenal gland was studied. Dexamethasone induces a transient increase of the adrenal glycogen content in a time and dose-dependent manner. The application of ACTH has no effect on the glycogen content. Surprisingly, the increase of the glycogen content induced by dexamethasone is completely blocked by the simultaneous application of ACTH."}
{"id": "PMID:218269", "title": "The integrative role of lecithin:cholesterol acyl transferase in triglyceride clearance.", "content": "There is evidence that not only lipoprotein lipase (LPL) but also lecithin:cholesterol acyl transferase (LCAT) are involved in the directional flow of triglyceride (TG) from endogenous very low density lipoproteins (VLDL) and chylomicrons as part of a general energy storage pathway. Evidence is given to suggest that LCAT plays an integrative role in this process.", "contents": "The integrative role of lecithin:cholesterol acyl transferase in triglyceride clearance. There is evidence that not only lipoprotein lipase (LPL) but also lecithin:cholesterol acyl transferase (LCAT) are involved in the directional flow of triglyceride (TG) from endogenous very low density lipoproteins (VLDL) and chylomicrons as part of a general energy storage pathway. Evidence is given to suggest that LCAT plays an integrative role in this process."}
{"id": "PMID:218270", "title": "Relationship between plasma lecithin:cholesterol acyltransferase activity and plasma triglyceride concentration in non-pregnant and pregnant Brazilian women.", "content": "Plasma concentrations of total, esterified and unesterified cholesterol, total phospholipid and triglyceride (TG) and lecithin:cholesterol acyltransferase (LCAT) activity were measured for 28 young non-pregnant women and for 31 young pregnant women from the city of Campina Grande, Brazil. During pregnancy plasma lipid levels and LCAT activity were successively increased and subsequently fell in post-partum samples. For both non-pregnant women and during each trimester of pregnancy and post-partum the activity of LCAT was significantly and positively correlated with the plasma concentrations of each lipid, the highest degree of correlation being found between LCAT and TG. No significant increase in plasma high density lipoprotein cholesterol occurred during pregnancy, and this parameter was not significantly correlated with LCAT activity in either pregnant or non-pregnant women. Instead low density lipoprotein (LDL) cholesterol was significantly increased in pregnancy and was significantly, positively, correlated with LCAT activity in both pregnant and non-pregnant women. The results emphasize the probable importance of LCAT in the metabolism of LDL and triglyceride-rich very low density lipoproteins, and pregnancy may provide a useful model for further studies of the physiological role of LCAT.", "contents": "Relationship between plasma lecithin:cholesterol acyltransferase activity and plasma triglyceride concentration in non-pregnant and pregnant Brazilian women. Plasma concentrations of total, esterified and unesterified cholesterol, total phospholipid and triglyceride (TG) and lecithin:cholesterol acyltransferase (LCAT) activity were measured for 28 young non-pregnant women and for 31 young pregnant women from the city of Campina Grande, Brazil. During pregnancy plasma lipid levels and LCAT activity were successively increased and subsequently fell in post-partum samples. For both non-pregnant women and during each trimester of pregnancy and post-partum the activity of LCAT was significantly and positively correlated with the plasma concentrations of each lipid, the highest degree of correlation being found between LCAT and TG. No significant increase in plasma high density lipoprotein cholesterol occurred during pregnancy, and this parameter was not significantly correlated with LCAT activity in either pregnant or non-pregnant women. Instead low density lipoprotein (LDL) cholesterol was significantly increased in pregnancy and was significantly, positively, correlated with LCAT activity in both pregnant and non-pregnant women. The results emphasize the probable importance of LCAT in the metabolism of LDL and triglyceride-rich very low density lipoproteins, and pregnancy may provide a useful model for further studies of the physiological role of LCAT."}
{"id": "PMID:218271", "title": "Failure of orotic acid to suppress activity of plasma lecithin:cholesterol acyltransferase.", "content": "There are theoretical reasons for postulating a relationship between turnover of triglyceride-rich lipoproteins and plasma cholesterol esterifying activity, and some experimental evidence exists to support such a hypothesis. Orotic acid has been given to rats to determine whether blocking the hepatic release of very-low-density lipoproteins would also reduce hepatic secretion of lecithin:cholesterol acyltransferase (LCAT). No evidence of such an effect was found. In a single human experiment orotic acid exerted only minimal effects on serum concentrations of lipoproteins, and LCAT activity was apparently unaffected.", "contents": "Failure of orotic acid to suppress activity of plasma lecithin:cholesterol acyltransferase. There are theoretical reasons for postulating a relationship between turnover of triglyceride-rich lipoproteins and plasma cholesterol esterifying activity, and some experimental evidence exists to support such a hypothesis. Orotic acid has been given to rats to determine whether blocking the hepatic release of very-low-density lipoproteins would also reduce hepatic secretion of lecithin:cholesterol acyltransferase (LCAT). No evidence of such an effect was found. In a single human experiment orotic acid exerted only minimal effects on serum concentrations of lipoproteins, and LCAT activity was apparently unaffected."}
{"id": "PMID:218272", "title": "Lecithin:cholesterol acyltransferase in partial ileal bypass rats.", "content": "In cholesterol-fed rats 6 weeks after partial ileal bypass, there was a significant (56%) decrease in serum cholesterol. Also, the concentration of very low density lipoprotein (VLDL) cholesterol was dramatically reduced after operation. However, after the operation, the percentage of high density lipoprotein (HDL) cholesterol was very high, i.e., 45% of the total lipoprotein cholesterol, whereas it was only 25% before operation. The initial rate of lecithin:cholesterol acyltransferase (LCAT), when assayed according to Stokke & Norum, showed an increase from 29 +/- 2 mumole/ml/h for non-operated cholesterol-fed controls to 121 +/- 7 mumole/ml/h after operation (p less than 0.01). After intestinal bypass the extrahepatic triglyceride lipase activity in serum was reduced by 60%, and there was no significant difference in hepatic triglyceride lipase. These observations indicate that in partial ileal bypass, the low serum cholesterol is due to the high HDL cholesterol and the high LCAT activity.", "contents": "Lecithin:cholesterol acyltransferase in partial ileal bypass rats. In cholesterol-fed rats 6 weeks after partial ileal bypass, there was a significant (56%) decrease in serum cholesterol. Also, the concentration of very low density lipoprotein (VLDL) cholesterol was dramatically reduced after operation. However, after the operation, the percentage of high density lipoprotein (HDL) cholesterol was very high, i.e., 45% of the total lipoprotein cholesterol, whereas it was only 25% before operation. The initial rate of lecithin:cholesterol acyltransferase (LCAT), when assayed according to Stokke & Norum, showed an increase from 29 +/- 2 mumole/ml/h for non-operated cholesterol-fed controls to 121 +/- 7 mumole/ml/h after operation (p less than 0.01). After intestinal bypass the extrahepatic triglyceride lipase activity in serum was reduced by 60%, and there was no significant difference in hepatic triglyceride lipase. These observations indicate that in partial ileal bypass, the low serum cholesterol is due to the high HDL cholesterol and the high LCAT activity."}
{"id": "PMID:218273", "title": "Plasma lecithin:cholesterol acyltransferase activity in hypophysectomized rats.", "content": "Hypophysectomy in rats induces a decrease in VLDL and HDL and an increase in LDL. To investigate the importance of lecithin:cholesterol acyltransferase (LCAT) for these changes, plasma LCAT activity was determined, both according to the methods of Stokke-Norum and Glomset-Wright. Plasma LCAT activity as assessed by both these methods decreased significantly after hypophysectomy, indicating a reduction in plasma enzyme concentration. Plasma total and free cholesterol increased slightly, while the concentration of cholesteryl esters and triglycerides remained unchanged. Blood sugar and FFA decreased. The osmotic resistance of the red cells was increased, and target cells were seen. There was a decrease in blood haemoglobin and haematocrit. Serum total protein concentration, electrophoresis, and plasma ALAT activity did not change. The observed changes in lipoproteins and LCAT following hypophysectomy can be partly explained by decreased liver secretion of both LCAT and VLDL. Because of the complex relationship between lipoproteins and LCAT, no clear-cut conclusions about the association between decreased HDL and LCAT can be drawn. The precise hormonal mechanisms controlling LCAT activity and lipoprotein metabolism remain to be solved.", "contents": "Plasma lecithin:cholesterol acyltransferase activity in hypophysectomized rats. Hypophysectomy in rats induces a decrease in VLDL and HDL and an increase in LDL. To investigate the importance of lecithin:cholesterol acyltransferase (LCAT) for these changes, plasma LCAT activity was determined, both according to the methods of Stokke-Norum and Glomset-Wright. Plasma LCAT activity as assessed by both these methods decreased significantly after hypophysectomy, indicating a reduction in plasma enzyme concentration. Plasma total and free cholesterol increased slightly, while the concentration of cholesteryl esters and triglycerides remained unchanged. Blood sugar and FFA decreased. The osmotic resistance of the red cells was increased, and target cells were seen. There was a decrease in blood haemoglobin and haematocrit. Serum total protein concentration, electrophoresis, and plasma ALAT activity did not change. The observed changes in lipoproteins and LCAT following hypophysectomy can be partly explained by decreased liver secretion of both LCAT and VLDL. Because of the complex relationship between lipoproteins and LCAT, no clear-cut conclusions about the association between decreased HDL and LCAT can be drawn. The precise hormonal mechanisms controlling LCAT activity and lipoprotein metabolism remain to be solved."}
{"id": "PMID:218274", "title": "Erythrocyte membrane alterations in lecithin:cholesterol acyltransferase deficiency.", "content": "Structural, compositional, and functional abnormalities were found in the erythrocyte membranes of homozygotes for LCAT deficiency. Similar but less pronounced abnormalities were also present in the heterozygotes for this disorder. Some of the membrane alterations, which included decreased osmotic fragility, changes in phospholipid composition, and membrane sulfydryl group latency, as well as changes in the activity of membrane p-nitrophenylphosphatases and acetylcholinesterase, may be secondary to the changes in plasma lipids. However, since plasma lipids (and LCAT activity) were normal in the hereozygotes, the existence in both the homo- and the heterozygotes of erythrocyte membrane abnormalities unrelated to plasma LCAT activity seems likely.", "contents": "Erythrocyte membrane alterations in lecithin:cholesterol acyltransferase deficiency. Structural, compositional, and functional abnormalities were found in the erythrocyte membranes of homozygotes for LCAT deficiency. Similar but less pronounced abnormalities were also present in the heterozygotes for this disorder. Some of the membrane alterations, which included decreased osmotic fragility, changes in phospholipid composition, and membrane sulfydryl group latency, as well as changes in the activity of membrane p-nitrophenylphosphatases and acetylcholinesterase, may be secondary to the changes in plasma lipids. However, since plasma lipids (and LCAT activity) were normal in the hereozygotes, the existence in both the homo- and the heterozygotes of erythrocyte membrane abnormalities unrelated to plasma LCAT activity seems likely."}
{"id": "PMID:218275", "title": "Familial lecithin:cholesterol acyltransferase deficiency. Further studies on plasma lipoproteins and plasma postheparin lipase activity of a patient with normal renal function.", "content": "Plasma lipoproteins and postheparin plasma were investigated in a patient with familial LCAT deficiency with normal renal function and without proteinuria. As revealed by gelfiltration the large molecular weight LDL2 was not present, and myelin structures were not found in LDL1 or LDL2 when she was on her ordinary diet. After 60--65% fat diet for one week the large molecular LDL2 was found, but only in low concentration. We have no explanation for the difference in the lipoprotein abnormalities of this patient and others with this disease. There is no major difference in the fat content in the ordinary diet of the Norwegian patients with familial LCAT deficiency, nor has our patient any clinical signs of malabsorption. Furthermore, there was no difference in lipoprotein lipase or hepatic lipase activity in postheparin plasma between our patient and others with the same disease. However, whereas hepatic lipase activity was within the reference values, lipoprotein lipase activity was rather low in all patients investigated. We suggest that impaired VLDL catabolism in plasma, because of LCAT deficiency and low lipoprotein lipase activity, may partly explain the low HDL concentration consistently found in  patients with familial LCAT deficiency.", "contents": "Familial lecithin:cholesterol acyltransferase deficiency. Further studies on plasma lipoproteins and plasma postheparin lipase activity of a patient with normal renal function. Plasma lipoproteins and postheparin plasma were investigated in a patient with familial LCAT deficiency with normal renal function and without proteinuria. As revealed by gelfiltration the large molecular weight LDL2 was not present, and myelin structures were not found in LDL1 or LDL2 when she was on her ordinary diet. After 60--65% fat diet for one week the large molecular LDL2 was found, but only in low concentration. We have no explanation for the difference in the lipoprotein abnormalities of this patient and others with this disease. There is no major difference in the fat content in the ordinary diet of the Norwegian patients with familial LCAT deficiency, nor has our patient any clinical signs of malabsorption. Furthermore, there was no difference in lipoprotein lipase or hepatic lipase activity in postheparin plasma between our patient and others with the same disease. However, whereas hepatic lipase activity was within the reference values, lipoprotein lipase activity was rather low in all patients investigated. We suggest that impaired VLDL catabolism in plasma, because of LCAT deficiency and low lipoprotein lipase activity, may partly explain the low HDL concentration consistently found in  patients with familial LCAT deficiency."}
{"id": "PMID:218276", "title": "Lipoproteins in plasma from patients with low LCAT activity due to biliary obstruction.", "content": "A high density lipoprotein (HDL) fraction, designated cholestatic HDL1, has been isolated by zonal ultracentrifugation from patients with long-standing biliary obstruction. This lipoprotein fraction consists exclusively of disc-shaped particles rich in phospholipid and unesterified cholesterol. The fatty acid composition of the minor cholesteryl ester fraction was characterized by a low content of linoleic acid. Apoprotein E was the dominating protein' component, while only small amounts of apolipoprotein A-I were found. Immunochemical studies of cholestatic HDL1 indicate that a considerable proportion of the particles contained apo E as its only protein constituent. All patients had a markedly reduced endogenous cholesterol-esterifying ability. The finding of apparently primary LpE particles in biliary obstruction may be related to this secondary LCAT deficiency.", "contents": "Lipoproteins in plasma from patients with low LCAT activity due to biliary obstruction. A high density lipoprotein (HDL) fraction, designated cholestatic HDL1, has been isolated by zonal ultracentrifugation from patients with long-standing biliary obstruction. This lipoprotein fraction consists exclusively of disc-shaped particles rich in phospholipid and unesterified cholesterol. The fatty acid composition of the minor cholesteryl ester fraction was characterized by a low content of linoleic acid. Apoprotein E was the dominating protein' component, while only small amounts of apolipoprotein A-I were found. Immunochemical studies of cholestatic HDL1 indicate that a considerable proportion of the particles contained apo E as its only protein constituent. All patients had a markedly reduced endogenous cholesterol-esterifying ability. The finding of apparently primary LpE particles in biliary obstruction may be related to this secondary LCAT deficiency."}
{"id": "PMID:218278", "title": "Relationship between high density lipoproteins and the rate of in vitro serum cholesterol esterification.", "content": "The rate of in vitro esterification of serum cholesterol and the concentrations of serum high density lipoprotein cholesterol (HDL-C) were measured in 18 women and 9 men, 74--95 years of age. Subjects in this age group can have HDL-C levels below accepted limits of normal. The subjects were divided into two groups, one with HDL-C less than 40 mg/dl and the other with HDL-C 40 mg/dl or higher. The rate of in vitro serum cholesterol esterification in the former group was 2.00 n. moles/ml/min, significantly higher (p less than 0.02) than 1.62 n. moles/ml/min present in the latter group. There was no correlation between the cholesterol esterification and a protein (s), which can produce an immune gamma globulin that completely inhibits in vitro serum cholesterol esterification. These findings are discussed with reference to the putative relationships between HDL-C and atherosclerosis.", "contents": "Relationship between high density lipoproteins and the rate of in vitro serum cholesterol esterification. The rate of in vitro esterification of serum cholesterol and the concentrations of serum high density lipoprotein cholesterol (HDL-C) were measured in 18 women and 9 men, 74--95 years of age. Subjects in this age group can have HDL-C levels below accepted limits of normal. The subjects were divided into two groups, one with HDL-C less than 40 mg/dl and the other with HDL-C 40 mg/dl or higher. The rate of in vitro serum cholesterol esterification in the former group was 2.00 n. moles/ml/min, significantly higher (p less than 0.02) than 1.62 n. moles/ml/min present in the latter group. There was no correlation between the cholesterol esterification and a protein (s), which can produce an immune gamma globulin that completely inhibits in vitro serum cholesterol esterification. These findings are discussed with reference to the putative relationships between HDL-C and atherosclerosis."}
{"id": "PMID:218281", "title": "Transfer and equilibration of LCAT-generated cholesteryl esters in human lipoproteins.", "content": "Non-enzymatic net transport of cholesteryl esters (CE) from HDL to VLDL in exchange for triglycerides has been reported in vitro. Likewise, in vivo observations have been adduced favoring the same process in human subjects and implicating LCAT product lipoproteins as carriers. Exchange of CE among lipoproteins is thought not to occur. In experiments in which LCAT-generated radioactive CE are formed from cholesterol dispersion in plasma, exchange to near equilibrium is observed. To better define this process, a labeling procedure employing lecithin: 3H-unesterified cholesterol single bilayer vesicles was devised. The order of lipoprotein labeling with isotopic CE is HDL greater than VLDL greater than LDL. After 19 hours of incubation, esters reached equilibrium. Control experiments with vesicles treated by purified LCAT showed that this result could not be explained by distribution of discrete ester-rich vesicle products or their binding to lipoproteins. Subfractionation of labeled lipoproteins on agarose columns confirmed completeness of equilibration, except for the HDL subfraction of smallest size, which is incompletely equilibrated. These results indicate that LCAT-generated CE are capable of equilibration among human lipoproteins.", "contents": "Transfer and equilibration of LCAT-generated cholesteryl esters in human lipoproteins. Non-enzymatic net transport of cholesteryl esters (CE) from HDL to VLDL in exchange for triglycerides has been reported in vitro. Likewise, in vivo observations have been adduced favoring the same process in human subjects and implicating LCAT product lipoproteins as carriers. Exchange of CE among lipoproteins is thought not to occur. In experiments in which LCAT-generated radioactive CE are formed from cholesterol dispersion in plasma, exchange to near equilibrium is observed. To better define this process, a labeling procedure employing lecithin: 3H-unesterified cholesterol single bilayer vesicles was devised. The order of lipoprotein labeling with isotopic CE is HDL greater than VLDL greater than LDL. After 19 hours of incubation, esters reached equilibrium. Control experiments with vesicles treated by purified LCAT showed that this result could not be explained by distribution of discrete ester-rich vesicle products or their binding to lipoproteins. Subfractionation of labeled lipoproteins on agarose columns confirmed completeness of equilibration, except for the HDL subfraction of smallest size, which is incompletely equilibrated. These results indicate that LCAT-generated CE are capable of equilibration among human lipoproteins."}
{"id": "PMID:218282", "title": "The role of high density lipoproteins in lecithin:cholesterol acyltransferase activity: perspectives from Tangier disease.", "content": "Lecithin:cholesterol acyltransferase activity and the lipid composition of VLDL and LDL were examined in five patients homozygous for Tangier disease. The following results were obtained: I. The percentage of cholesterol that was esterified was similar in Taniger and control lipoproteins. II. Linoleic acid was the predominant fatty acid constituent of cholesteryl esters in Tangier plasma. III. Molar cholesterol esterification rates in Tangier plasma were reduced; however, fractional rates of cholesterol esterification were equal to or exceeded those of control plasma. IV. In vitro addition of apoprotein A-I and isolated lipoproteins led to a concentration-dependent increase in the initial rates of cholesterol esterification in Tangier plasma. It is concluded that HDL is not an exclusive substrate for the LCAT reaction, and that cholesterol esterification is not impaired in Tangier plasma.", "contents": "The role of high density lipoproteins in lecithin:cholesterol acyltransferase activity: perspectives from Tangier disease. Lecithin:cholesterol acyltransferase activity and the lipid composition of VLDL and LDL were examined in five patients homozygous for Tangier disease. The following results were obtained: I. The percentage of cholesterol that was esterified was similar in Taniger and control lipoproteins. II. Linoleic acid was the predominant fatty acid constituent of cholesteryl esters in Tangier plasma. III. Molar cholesterol esterification rates in Tangier plasma were reduced; however, fractional rates of cholesterol esterification were equal to or exceeded those of control plasma. IV. In vitro addition of apoprotein A-I and isolated lipoproteins led to a concentration-dependent increase in the initial rates of cholesterol esterification in Tangier plasma. It is concluded that HDL is not an exclusive substrate for the LCAT reaction, and that cholesterol esterification is not impaired in Tangier plasma."}
{"id": "PMID:218284", "title": "Regional localization of the gene for human phosphoribosylpyrophosphate synthetase on the X chromosome.", "content": "Sixty-eight independent hybrid clones were isolated after irradiated normal human lymphocytes were fused with Chinese hamster fibroblasts lacking hypoxanthine-guanine phosphoribosyltransferase activity. The cells were grown under selective conditions requiring retention of the X chromosome-linked locus for human hypoxanthine-guanine phosphoribosyltransferase. The frequency and patterns of cotransference of human phosphoribosylpyrophosphate synthetase with the selected marker and with additional X-linked enzymatic markers confirm X linkage of the structural gene for human phosphoribosylpyrophosphate synthetase and support assignment of this gene to a position on the long arm of the X, between the loci for alpha-galactosidase and hypoxanthine-guanine phosphoribosyltransferase.", "contents": "Regional localization of the gene for human phosphoribosylpyrophosphate synthetase on the X chromosome. Sixty-eight independent hybrid clones were isolated after irradiated normal human lymphocytes were fused with Chinese hamster fibroblasts lacking hypoxanthine-guanine phosphoribosyltransferase activity. The cells were grown under selective conditions requiring retention of the X chromosome-linked locus for human hypoxanthine-guanine phosphoribosyltransferase. The frequency and patterns of cotransference of human phosphoribosylpyrophosphate synthetase with the selected marker and with additional X-linked enzymatic markers confirm X linkage of the structural gene for human phosphoribosylpyrophosphate synthetase and support assignment of this gene to a position on the long arm of the X, between the loci for alpha-galactosidase and hypoxanthine-guanine phosphoribosyltransferase."}
{"id": "PMID:218285", "title": "Thyroid hormone action at the cellular level.", "content": "A large body of circumstantial evidence suggests that the basic unit of thyroid hormone action is the triiodothyronine nuclear receptor complex. This complex stimulates the formation, directly or indirectly, of a diversity of messenger RNA (mRNA) sequences. A generalized increase in mRNA as well as a disproportionate increase in a limited number of RNA sequences have been demonstrated. Regulation of thyroid hormone effects may be carried out largely at a local cellular level. Highly selective alterations in sensitivity to the triiodothyronine nuclear receptor complex may occur at specific target genes. Metabolic factors and hormones participate in such regulation. In a given tissue, alterations in the total number of receptor sites has not been shown to be useful as an index of thyroid hormone response, and local modulation of the response to the triiodothyronine receptor complex by a variety of factors other than triiodothyronine may be carried out at a postreceptor level.", "contents": "Thyroid hormone action at the cellular level. A large body of circumstantial evidence suggests that the basic unit of thyroid hormone action is the triiodothyronine nuclear receptor complex. This complex stimulates the formation, directly or indirectly, of a diversity of messenger RNA (mRNA) sequences. A generalized increase in mRNA as well as a disproportionate increase in a limited number of RNA sequences have been demonstrated. Regulation of thyroid hormone effects may be carried out largely at a local cellular level. Highly selective alterations in sensitivity to the triiodothyronine nuclear receptor complex may occur at specific target genes. Metabolic factors and hormones participate in such regulation. In a given tissue, alterations in the total number of receptor sites has not been shown to be useful as an index of thyroid hormone response, and local modulation of the response to the triiodothyronine receptor complex by a variety of factors other than triiodothyronine may be carried out at a postreceptor level."}
{"id": "PMID:218286", "title": "Polyoma virion and capsid crystal structures.", "content": "X-ray diffraction shows that complete virus particles and empty capsids crystallize isomorphously. The surface morphology of the protein coat, as revealed by electron microscopy, is the dominant structural feature determining the intensity of x-ray reflections to a resolution of approximately 30 angstroms. The structure and variability of the viral chromatin core can now be analyzed by comparison of electron density maps.", "contents": "Polyoma virion and capsid crystal structures. X-ray diffraction shows that complete virus particles and empty capsids crystallize isomorphously. The surface morphology of the protein coat, as revealed by electron microscopy, is the dominant structural feature determining the intensity of x-ray reflections to a resolution of approximately 30 angstroms. The structure and variability of the viral chromatin core can now be analyzed by comparison of electron density maps."}
{"id": "PMID:218289", "title": "Amino acid sequence homology between histone H5 and murine leukemia virus phosphoprotein p12.", "content": "The amino terminal acid sequences of several mouse leukemia virus phosphoproteins (p12) show definite homology with the amino terminal conserved region of H5 histones, the phosphorylated nuclear proteins of nucleated erythrocytes. Differences in the amino acid compositions of the two groups of proteins seem to rule out the possibility that they evolved from a single common ancestral gene. The finding of sequence homology between viral p12's and cellular histones, however, is consistent with evolution of retrovirus structural proteins by a process of differentiation from preexisting cellular genes. The conserved primary and secondary structure at the amino terminal region, common to both groups of proteins, may be related to their common function of nucleic acid binding modulated by phosphorylation.", "contents": "Amino acid sequence homology between histone H5 and murine leukemia virus phosphoprotein p12. The amino terminal acid sequences of several mouse leukemia virus phosphoproteins (p12) show definite homology with the amino terminal conserved region of H5 histones, the phosphorylated nuclear proteins of nucleated erythrocytes. Differences in the amino acid compositions of the two groups of proteins seem to rule out the possibility that they evolved from a single common ancestral gene. The finding of sequence homology between viral p12's and cellular histones, however, is consistent with evolution of retrovirus structural proteins by a process of differentiation from preexisting cellular genes. The conserved primary and secondary structure at the amino terminal region, common to both groups of proteins, may be related to their common function of nucleic acid binding modulated by phosphorylation."}
{"id": "PMID:218290", "title": "[Contribution to the study of endocrinopathies in black Africans (author's transl)].", "content": "For a long time endocrine pathology was unrecognized or even denied to exist in Black Africans, but this is not true. It seems to be recognized more frequently since medicalization has increased. This pathology does not present any particularities. Hyperthyroidism appears frequently, at least in urban areas. A series of 87 personal cases has permitted a review of the principal clinical and biological aspects; myasthenia seems to be particularly important; radical treatment is preferred over prolonged medical treatment which is not within the financial possibilities of our patients. There have been 30 observations of cortico-adrenal anomalies of which 7 known personally. It must be noted that the Black living in his traditional rural environment presents a certain degree of physiological hypocorticism with respect to whites and especially Blacks of higher social standing. Pathological hypocorticism is essentially due to tuberculosis; the melanodermia is evident to an alert observer. Metabolic hypercorticism produces the usual manifestations. Only 9 cases of Sheehan syndrome have been reported (5 personal). In the Black African woman, it appears earlier than in Europe often due to premature nuptiulity and the higher incidence of tachyparity. One is surprised that this syndrome is detected so rarely; it is, without a doubt, often well tolerated during a long period of time therefore goes undetected.", "contents": "[Contribution to the study of endocrinopathies in black Africans (author's transl)]. For a long time endocrine pathology was unrecognized or even denied to exist in Black Africans, but this is not true. It seems to be recognized more frequently since medicalization has increased. This pathology does not present any particularities. Hyperthyroidism appears frequently, at least in urban areas. A series of 87 personal cases has permitted a review of the principal clinical and biological aspects; myasthenia seems to be particularly important; radical treatment is preferred over prolonged medical treatment which is not within the financial possibilities of our patients. There have been 30 observations of cortico-adrenal anomalies of which 7 known personally. It must be noted that the Black living in his traditional rural environment presents a certain degree of physiological hypocorticism with respect to whites and especially Blacks of higher social standing. Pathological hypocorticism is essentially due to tuberculosis; the melanodermia is evident to an alert observer. Metabolic hypercorticism produces the usual manifestations. Only 9 cases of Sheehan syndrome have been reported (5 personal). In the Black African woman, it appears earlier than in Europe often due to premature nuptiulity and the higher incidence of tachyparity. One is surprised that this syndrome is detected so rarely; it is, without a doubt, often well tolerated during a long period of time therefore goes undetected."}
{"id": "PMID:218291", "title": "[Early and unusual presentation of temporal arteritis. A report of 7 cases (author's transl)].", "content": "The authors report 7 cases of temporal arteritis, proved by biopsy, with unusual early symptoms. They emphasize dental extraction as a possible incitant of the disease. Diagnosis is very often overlooked when local symptoms of involvment of temporal arteries are lacking. Various head and neck pain, fever of unexplained origin, weight loss, when associated with erythrocyte sedimentation rate greater than 50 mm, should convince the physician to biopsy the temporal artery of people over the age of 60. Steroid therapy must begin as soon as diagnosis is made.", "contents": "[Early and unusual presentation of temporal arteritis. A report of 7 cases (author's transl)]. The authors report 7 cases of temporal arteritis, proved by biopsy, with unusual early symptoms. They emphasize dental extraction as a possible incitant of the disease. Diagnosis is very often overlooked when local symptoms of involvment of temporal arteries are lacking. Various head and neck pain, fever of unexplained origin, weight loss, when associated with erythrocyte sedimentation rate greater than 50 mm, should convince the physician to biopsy the temporal artery of people over the age of 60. Steroid therapy must begin as soon as diagnosis is made."}
{"id": "PMID:218292", "title": "[Thrombocytosis and primary bronchial carcinoma. Study about 164 patients with bronchial carcinoma (author's transl)].", "content": "This paper is relating the study of 164 patients with primary and proved bronchial carcinoma. A thrombocytosis superior to 400,000/mm3 was observed in 36.6 p. cent of cases. But no statistic relation was found between the histological type of tumor, a biological inflammatory state, the existence of metastasis and thrombocytosis. However thrombocytosis was more frequently observed among anaemic and hyposideremic patients. No significantly changes of paO2 and paCO2 were noted in patients with thrombocytosis. The systematic platelet count could be of an interest in the interpretation of some thoracic radiography.", "contents": "[Thrombocytosis and primary bronchial carcinoma. Study about 164 patients with bronchial carcinoma (author's transl)]. This paper is relating the study of 164 patients with primary and proved bronchial carcinoma. A thrombocytosis superior to 400,000/mm3 was observed in 36.6 p. cent of cases. But no statistic relation was found between the histological type of tumor, a biological inflammatory state, the existence of metastasis and thrombocytosis. However thrombocytosis was more frequently observed among anaemic and hyposideremic patients. No significantly changes of paO2 and paCO2 were noted in patients with thrombocytosis. The systematic platelet count could be of an interest in the interpretation of some thoracic radiography."}
{"id": "PMID:218293", "title": "[The clinical course of late cutaneous porphyria (author's transl)].", "content": "Study of the course of 23 patients, with late cutaneous porphyria, after 3 to 8 years. So, we remark: the clear improvement of the majority of the patients, from whom a quarter appear entirely cured, the more satisfactory affects of bleeding and alkali-therapy, the absence of reference with the course of chronic alcoholism the absence of visceral complication of porphyria.", "contents": "[The clinical course of late cutaneous porphyria (author's transl)]. Study of the course of 23 patients, with late cutaneous porphyria, after 3 to 8 years. So, we remark: the clear improvement of the majority of the patients, from whom a quarter appear entirely cured, the more satisfactory affects of bleeding and alkali-therapy, the absence of reference with the course of chronic alcoholism the absence of visceral complication of porphyria."}
{"id": "PMID:218294", "title": "[Fine needle aspiration biopsy in pneumology. 351 punctures].", "content": "From 351 transthoracic punctures with a fine needle, the authors determine their method of exam. The cytologic study of the samples permits a positive diagnosis of pulmonary opacity for 60 p. cent to 70 p. cent of the cases. The rentability reaches 89 p. cent for malignant lesions. The complications with the fine needle are very unusual comparatively to the technics allowing a histologic study, although rentability is equal for these two methods.", "contents": "[Fine needle aspiration biopsy in pneumology. 351 punctures]. From 351 transthoracic punctures with a fine needle, the authors determine their method of exam. The cytologic study of the samples permits a positive diagnosis of pulmonary opacity for 60 p. cent to 70 p. cent of the cases. The rentability reaches 89 p. cent for malignant lesions. The complications with the fine needle are very unusual comparatively to the technics allowing a histologic study, although rentability is equal for these two methods."}
{"id": "PMID:218295", "title": "[Preventive treatment of thromboembolic disease in thoracic surgery (author's transl)].", "content": "The aim of the present work is twofold: 1) to find a simple method of diagnosing a genuine risk of post operative thromboembolic disease: the level of platellets and of fibrine, the cephaline-kaolin test, the thromboelastogram and the para-coagulation tests were not considered satisfactory by authors. Only the isotopic detection of venous thrombosis is able to confirm the value of a given preventive treatment; 2) to achieve an effective prevemtive treatment: the pre and post-operative heparin therapy (an adaptation of Kakkar's method) eliminates the clinical accidents, reduces the number of isotopic venous thrombosis, but might increase the incidence of hemorrage.", "contents": "[Preventive treatment of thromboembolic disease in thoracic surgery (author's transl)]. The aim of the present work is twofold: 1) to find a simple method of diagnosing a genuine risk of post operative thromboembolic disease: the level of platellets and of fibrine, the cephaline-kaolin test, the thromboelastogram and the para-coagulation tests were not considered satisfactory by authors. Only the isotopic detection of venous thrombosis is able to confirm the value of a given preventive treatment; 2) to achieve an effective prevemtive treatment: the pre and post-operative heparin therapy (an adaptation of Kakkar's method) eliminates the clinical accidents, reduces the number of isotopic venous thrombosis, but might increase the incidence of hemorrage."}
{"id": "PMID:218296", "title": "[Local tolerance of subcutaneous heparin. Double-blind comparison of calcium and sodium heparins (author's transl)].", "content": "One hundred and twelve subcutaneous injections of concentrated heparin (25,000 IU/ml), half in sodium heparin and half in calciparine, both with an identical heparin cation, were given in doses varying from 0.2 ml to 0.5 ml by a single operator in a double-blind study to assess the comparative local tolerance of the two heparin salts. The occurrence of bruising at the point of injection, more frequent with sodium heparin than with Calciparine, proved to be the distinguishing factor. Overall after 48 hours, 31 hematomas were observed with the sodium salt versus 20 with calciparine. McNemar's test of comparing matched proportions confirms this result (p = 0.03) and, with the order of the two treatments taken into consideration, J.J. Gart's exact test gives p = 0.0101.", "contents": "[Local tolerance of subcutaneous heparin. Double-blind comparison of calcium and sodium heparins (author's transl)]. One hundred and twelve subcutaneous injections of concentrated heparin (25,000 IU/ml), half in sodium heparin and half in calciparine, both with an identical heparin cation, were given in doses varying from 0.2 ml to 0.5 ml by a single operator in a double-blind study to assess the comparative local tolerance of the two heparin salts. The occurrence of bruising at the point of injection, more frequent with sodium heparin than with Calciparine, proved to be the distinguishing factor. Overall after 48 hours, 31 hematomas were observed with the sodium salt versus 20 with calciparine. McNemar's test of comparing matched proportions confirms this result (p = 0.03) and, with the order of the two treatments taken into consideration, J.J. Gart's exact test gives p = 0.0101."}
{"id": "PMID:218297", "title": "[Surgical treatment of Wolff-Parkinson-White syndrome (author's transl)].", "content": "This report relates the surgical experience with 75 patients with WPW. The patients' symptoms were either SVT alone or SVT associated with a pathway with a lethal potential. In some, the Kent pathway caused SVT but did not cause cause pre-excitation. In others, multiple pathways were found. Success has been achieved in 35 of the last 36 patients with freewall pathways treated by surgery. Problems still remain with the posterior septal group. The indications for operation have been broadened to include all patients with significant symptoms.", "contents": "[Surgical treatment of Wolff-Parkinson-White syndrome (author's transl)]. This report relates the surgical experience with 75 patients with WPW. The patients' symptoms were either SVT alone or SVT associated with a pathway with a lethal potential. In some, the Kent pathway caused SVT but did not cause cause pre-excitation. In others, multiple pathways were found. Success has been achieved in 35 of the last 36 patients with freewall pathways treated by surgery. Problems still remain with the posterior septal group. The indications for operation have been broadened to include all patients with significant symptoms."}
{"id": "PMID:218298", "title": "[Bi-tissular malignant tumors of the lung. 2 cases].", "content": "Two new cases of multiple components pulmonary carcinoma are described: a pneumoblastoma and a epitheliosarcoma. Differenciating clinical features and nosological problems are recelled, allowing to discuss the classification of these two observations.", "contents": "[Bi-tissular malignant tumors of the lung. 2 cases]. Two new cases of multiple components pulmonary carcinoma are described: a pneumoblastoma and a epitheliosarcoma. Differenciating clinical features and nosological problems are recelled, allowing to discuss the classification of these two observations."}
{"id": "PMID:218299", "title": "[Paraneoplastic syndromes in carcinoma of the kidney (author's transl)].", "content": "The authors present a group of patients with renal carcinoma in whom there were paraneoplastic signs such as fever, liver failure, hypertension and polycythemia. They noted, moreover, the most important clinical aspects, evaluating the incidence of these signs in relation to the course and diagnosis. They discuss also the frequency of presentation of each of these paraneoplastic manifestations, commenting on the various theories which have been suggested to explain them.", "contents": "[Paraneoplastic syndromes in carcinoma of the kidney (author's transl)]. The authors present a group of patients with renal carcinoma in whom there were paraneoplastic signs such as fever, liver failure, hypertension and polycythemia. They noted, moreover, the most important clinical aspects, evaluating the incidence of these signs in relation to the course and diagnosis. They discuss also the frequency of presentation of each of these paraneoplastic manifestations, commenting on the various theories which have been suggested to explain them."}
{"id": "PMID:218300", "title": "[Second malignacies complicating Hodgkin's disease. 1 case].", "content": "It is reported a case of long-term Hodgkin's disease treated with several courses of radiotherapy and chemotherapy and complicated with acute myeloblastic leukemia. Authors discuss the responsability of treatment immunosuppression, viral infections, levamizole and genetic factor.", "contents": "[Second malignacies complicating Hodgkin's disease. 1 case]. It is reported a case of long-term Hodgkin's disease treated with several courses of radiotherapy and chemotherapy and complicated with acute myeloblastic leukemia. Authors discuss the responsability of treatment immunosuppression, viral infections, levamizole and genetic factor."}
{"id": "PMID:218301", "title": "[Acute ulcerative colitis associated with cytomegalic inclusion virus in a non-immunodepressed patient (author's transl)].", "content": "A new case of acute ulcerative colitis associated with cytomegalic inclusion virus within the colonic wall is reported. Some unusual features are discussed, such as the absent defect in cellular or humoral immunity, the location of the lesion which were limited to the sigmoid colon, and the fatal outcome of the disease. The possible pathogenic relationship between cytomegalic infection and acute a chronic ulcerative colitis are reviewed.", "contents": "[Acute ulcerative colitis associated with cytomegalic inclusion virus in a non-immunodepressed patient (author's transl)]. A new case of acute ulcerative colitis associated with cytomegalic inclusion virus within the colonic wall is reported. Some unusual features are discussed, such as the absent defect in cellular or humoral immunity, the location of the lesion which were limited to the sigmoid colon, and the fatal outcome of the disease. The possible pathogenic relationship between cytomegalic infection and acute a chronic ulcerative colitis are reviewed."}
{"id": "PMID:218302", "title": "[The treatment of acute myeloblastic leukemia in the elderly patients (author's transl)].", "content": "Thirty eight patients over 60 years with acute myeloblastic leukemia are studied. 16 p. cent (3 out 19) of the patients 60--69 year-old and 42 p. cent (8 out 19) over 70 died before any treatment or effective chemotherapy. Among the patients who received and effective chemotherapy, 48 p. cent responded and 7 complete remissions were obtained. The rate of responders is lower in oldest patients; nevertheless when a response whether complete or partial is observed, the survival of responders is dramatically improved. This invites to treat with effective chemotherapies every patients suffering from acute myeloblastic leukemia in the elderly. However, the comfort and the quality of survival must not be omitted.", "contents": "[The treatment of acute myeloblastic leukemia in the elderly patients (author's transl)]. Thirty eight patients over 60 years with acute myeloblastic leukemia are studied. 16 p. cent (3 out 19) of the patients 60--69 year-old and 42 p. cent (8 out 19) over 70 died before any treatment or effective chemotherapy. Among the patients who received and effective chemotherapy, 48 p. cent responded and 7 complete remissions were obtained. The rate of responders is lower in oldest patients; nevertheless when a response whether complete or partial is observed, the survival of responders is dramatically improved. This invites to treat with effective chemotherapies every patients suffering from acute myeloblastic leukemia in the elderly. However, the comfort and the quality of survival must not be omitted."}
{"id": "PMID:218303", "title": "[A useful addition to the cyto-diagnosis of hemorraegic pleural fluids: the histological examination of the clot (author's transl)].", "content": "As an addition to classical cytology, the authors propose this histological examination of the clot, which is frequently observed in pleural fluids. This clot is taken before any centrifugation which might alter the former cellular groups. This method has been undertaken on 98 cases out of 196. Only 61 clots were prepared according to the histological technique, out of which 24 were positive. The only criteria taken under consideration were the histioid, trabecular or glandular groups. This technique enables the authors to a precise diagnosis in about one third of the suspicious cases and, besides, to discover a few positive cases which had escaped the routine technique.", "contents": "[A useful addition to the cyto-diagnosis of hemorraegic pleural fluids: the histological examination of the clot (author's transl)]. As an addition to classical cytology, the authors propose this histological examination of the clot, which is frequently observed in pleural fluids. This clot is taken before any centrifugation which might alter the former cellular groups. This method has been undertaken on 98 cases out of 196. Only 61 clots were prepared according to the histological technique, out of which 24 were positive. The only criteria taken under consideration were the histioid, trabecular or glandular groups. This technique enables the authors to a precise diagnosis in about one third of the suspicious cases and, besides, to discover a few positive cases which had escaped the routine technique."}
{"id": "PMID:218304", "title": "[Hospitalisation at home of children seen in a pediatric outpatients (author's transl)].", "content": "The authors relate their experience of hospitalisation at home of 74 children selected in a pediatric outpatients over a period of 5 years. They show the advantages of this method of care which are much greater than the few disadvantages and regret that it is not used more often.", "contents": "[Hospitalisation at home of children seen in a pediatric outpatients (author's transl)]. The authors relate their experience of hospitalisation at home of 74 children selected in a pediatric outpatients over a period of 5 years. They show the advantages of this method of care which are much greater than the few disadvantages and regret that it is not used more often."}
{"id": "PMID:218312", "title": "Obstruction of the abdominal aorta by a primary retroperitoneal tumor.", "content": "An angiographically demonstrated case of total occlusion of the abdominal aorta by a malignant retroperitoneal tumor is presented. Surgical exploration revealed a diffuse tumor of the retroperitoneum involving the wall and lumen of the abdominal aorta and vena cava, respectively. Histologic and ultrastructural evaluation of the tumor established a diagnosis of malignant fibrous histiocytoma. Total occlusion of the abdominal aorta thus represents another angiographic finding in retroperitoneal tumors.", "contents": "Obstruction of the abdominal aorta by a primary retroperitoneal tumor. An angiographically demonstrated case of total occlusion of the abdominal aorta by a malignant retroperitoneal tumor is presented. Surgical exploration revealed a diffuse tumor of the retroperitoneum involving the wall and lumen of the abdominal aorta and vena cava, respectively. Histologic and ultrastructural evaluation of the tumor established a diagnosis of malignant fibrous histiocytoma. Total occlusion of the abdominal aorta thus represents another angiographic finding in retroperitoneal tumors."}
{"id": "PMID:218314", "title": "Ultrasonography in trophoblastic disease.", "content": "Five cases of trophoblastic disease evaluated by gray scale ultrasonography were reviewed. The ultrasonographic findings of trophoblastic disease are discussed and illustrated. Theca-lutein cyst is reported to be associated with high levels of human chorionic gonadotropin (HCG). From our limited study, there was no correlation between theca-lutein cyst formation or size and the HCG titers of the patients at the time of examination. Molar evacuation must be followed in correlation with abdominal ultrasound and frequent monitoring of HCG levels.", "contents": "Ultrasonography in trophoblastic disease. Five cases of trophoblastic disease evaluated by gray scale ultrasonography were reviewed. The ultrasonographic findings of trophoblastic disease are discussed and illustrated. Theca-lutein cyst is reported to be associated with high levels of human chorionic gonadotropin (HCG). From our limited study, there was no correlation between theca-lutein cyst formation or size and the HCG titers of the patients at the time of examination. Molar evacuation must be followed in correlation with abdominal ultrasound and frequent monitoring of HCG levels."}
{"id": "PMID:218315", "title": "Antibody to hepatitis B surface antigen is not cytotoxic to antigen-secreting hepatocytes.", "content": "A continuously growing cell line which produces hepatitis B surface antigen was grown in the presence of antibody to the surface antigen. Antibody from animal and human sources was used. Neither growth rate nor cell morphology was affected and the cells did not inactivate the antibody over a 4-day incubation period. The surface antigen produced was specifically neutralized. These results suggest that hepatic injury occurring in response to hepatitis B virus infection is not mediated by humoral immunity to the surface antigen.", "contents": "Antibody to hepatitis B surface antigen is not cytotoxic to antigen-secreting hepatocytes. A continuously growing cell line which produces hepatitis B surface antigen was grown in the presence of antibody to the surface antigen. Antibody from animal and human sources was used. Neither growth rate nor cell morphology was affected and the cells did not inactivate the antibody over a 4-day incubation period. The surface antigen produced was specifically neutralized. These results suggest that hepatic injury occurring in response to hepatitis B virus infection is not mediated by humoral immunity to the surface antigen."}
{"id": "PMID:218319", "title": "\"Blue bodies\" in a case of cryptogenic fibrosing alveolitis (desquamative type) an ultra-structural study.", "content": "A patient with cryptogenic fibrosing alveolitis, with both mural and desquamative features, had two lung biopsies at the times of coronary artery surgery. These lung specimens were studied, using light and electron microscopy, with immunofluorescence techniques and electron microanalysis. In addition to the typical changes of cryptogenic fibrosing alveolitis previously reported, we found \"blue-staining bodies\" within alveolar macrophages and giant cells. These bodies were 15--25 micrometer in diameter with an iron rich outer rim and core of connective tissue mucin--possibly chondroitin sulphate or dermatan sulphate. It seems unlikely that these \"blue bodies\" were due to fibreglass dust to which the patients had had a trivial exposure, but their exact nature and significance remains unclear.", "contents": "\"Blue bodies\" in a case of cryptogenic fibrosing alveolitis (desquamative type) an ultra-structural study. A patient with cryptogenic fibrosing alveolitis, with both mural and desquamative features, had two lung biopsies at the times of coronary artery surgery. These lung specimens were studied, using light and electron microscopy, with immunofluorescence techniques and electron microanalysis. In addition to the typical changes of cryptogenic fibrosing alveolitis previously reported, we found \"blue-staining bodies\" within alveolar macrophages and giant cells. These bodies were 15--25 micrometer in diameter with an iron rich outer rim and core of connective tissue mucin--possibly chondroitin sulphate or dermatan sulphate. It seems unlikely that these \"blue bodies\" were due to fibreglass dust to which the patients had had a trivial exposure, but their exact nature and significance remains unclear."}
{"id": "PMID:218320", "title": "[Vaccination using an inactivated vaccine on a pig-breeding farm infected with the virus causing Aujeszky's disease (author's transl)].", "content": "When Aujeszky's disease was detected on a large pig-breeding farm, all normal sows and boars were vaccinated with an ethyl-ethylene-imine (EEI) vaccine produced in the Bundesforschungsanstalt f\u00fcr Viruskrankheiten der Tiere (Federal Research Institute for Viruses Diseases in Animals) in T\u00fcbbingen, Western Germany. The vaccine contained DEAE dextran as an adjuvant. The vaccine was inoculated twice by intramuscular route at a three weeks' interval, 5 ml. being inoculated at one time. Hyperimmune serum was inoculated in young pigs. In addition, hygienic procedures were adopted, consisting in disinfection and isolation. The disease was successfully controlled within eight weeks. Sows which developed Aujeszky's disease showed hardly any symptoms suggesting lesions of the central nervous system. Pulmonary lesions were the outstanding clinical feature. The semen quality of the affected male swine had markedly deteriorated. This was resorted to normal, however, within from five to ten weeks. The incidence of abortion and piglet mortality were low. In view of the results of virological and serological studies, it was concluded that the persistence of this strain of virus (causing Aujeszky's disease) was very slight.", "contents": "[Vaccination using an inactivated vaccine on a pig-breeding farm infected with the virus causing Aujeszky's disease (author's transl)]. When Aujeszky's disease was detected on a large pig-breeding farm, all normal sows and boars were vaccinated with an ethyl-ethylene-imine (EEI) vaccine produced in the Bundesforschungsanstalt f\u00fcr Viruskrankheiten der Tiere (Federal Research Institute for Viruses Diseases in Animals) in T\u00fcbbingen, Western Germany. The vaccine contained DEAE dextran as an adjuvant. The vaccine was inoculated twice by intramuscular route at a three weeks' interval, 5 ml. being inoculated at one time. Hyperimmune serum was inoculated in young pigs. In addition, hygienic procedures were adopted, consisting in disinfection and isolation. The disease was successfully controlled within eight weeks. Sows which developed Aujeszky's disease showed hardly any symptoms suggesting lesions of the central nervous system. Pulmonary lesions were the outstanding clinical feature. The semen quality of the affected male swine had markedly deteriorated. This was resorted to normal, however, within from five to ten weeks. The incidence of abortion and piglet mortality were low. In view of the results of virological and serological studies, it was concluded that the persistence of this strain of virus (causing Aujeszky's disease) was very slight."}
{"id": "PMID:218327", "title": "The 1977 outbreak of bluetongue in Cyprus.", "content": "Bluetongue outbreaks, ranging from isolated cases to widespread infections, have occurred in Cyprus in about half of the years since 1924. Serious outbreaks occurred in 1924, 1939, 1943, 1946, 1951, and 1965. Most cases occurred in September, October, November and December. The last outbreak prior to 1977 was in 1969. Virus types isolated in the past were types 3 and 4. In 1977 the outbreak was serious, affecting 13.1 per cent of 27,837 in-contact sheep; these were scattered in 303 flocks of 65 villages throughout the Government-controlled area. The virus type isolated was type 4. Culicoides were involved in bluetongue transmission in the island.", "contents": "The 1977 outbreak of bluetongue in Cyprus. Bluetongue outbreaks, ranging from isolated cases to widespread infections, have occurred in Cyprus in about half of the years since 1924. Serious outbreaks occurred in 1924, 1939, 1943, 1946, 1951, and 1965. Most cases occurred in September, October, November and December. The last outbreak prior to 1977 was in 1969. Virus types isolated in the past were types 3 and 4. In 1977 the outbreak was serious, affecting 13.1 per cent of 27,837 in-contact sheep; these were scattered in 303 flocks of 65 villages throughout the Government-controlled area. The virus type isolated was type 4. Culicoides were involved in bluetongue transmission in the island."}
{"id": "PMID:218328", "title": "Possible histologic markers for early and late stages of breast cancer.", "content": "The degree of productive fibrosis, amount of lymphoid infiltrate and nuclear grade have been studied in 492 consecutive cases of duct-infiltrating breast cancer. It has been found that highly significant relationships exist between these morphologic parameters of breast cancer: lymphoid infiltrate is directly related to nuclear anaplasia and antagonized by productive fibrosis; conversely, productive fibrosis is inversely related to nuclear anaplasia and antagonized by lymphoid infiltrate. Significant inverse relationships between productive fibrosis and lymphoid infiltrate persist in tumors that have the same nuclear grade. It is suggested that lymphoid infiltrate and productive fibrosis are suitable candidates as morphologic markers to estimate the age of breast cancer, while the nuclear grade is a suitable tool to identify subgroups with different behaviour in the NOS (not otherwise specified) category of breast cancer.", "contents": "Possible histologic markers for early and late stages of breast cancer. The degree of productive fibrosis, amount of lymphoid infiltrate and nuclear grade have been studied in 492 consecutive cases of duct-infiltrating breast cancer. It has been found that highly significant relationships exist between these morphologic parameters of breast cancer: lymphoid infiltrate is directly related to nuclear anaplasia and antagonized by productive fibrosis; conversely, productive fibrosis is inversely related to nuclear anaplasia and antagonized by lymphoid infiltrate. Significant inverse relationships between productive fibrosis and lymphoid infiltrate persist in tumors that have the same nuclear grade. It is suggested that lymphoid infiltrate and productive fibrosis are suitable candidates as morphologic markers to estimate the age of breast cancer, while the nuclear grade is a suitable tool to identify subgroups with different behaviour in the NOS (not otherwise specified) category of breast cancer."}
{"id": "PMID:218332", "title": "Studies on intrarenal prostaglandins. Effect of unilateral renal artery constriction on lipid droplets in the medullary interstitial cells of the 'opposite' kidney in rabbits.", "content": "The unilateral renal artery in rabbits was constricted, and lipid droplet count in the medullary interstitial cells of the 'opposite' kidney was performed 1 week after surgery. Lipid droplet count in hypertensive rabbits was less than that in both nonhypertensive and normal rabbits and was inversely proportional to the mean blood pressure. Lipid droplet count was significantly correlated with the juxtaglomerular granulation index and the sodium content in the inner medulla. The present results suggest that, in the opposite kidney of rabbits hypertensive due to unilateral constriction of the renal artery, the enhanced release of prostaglandins and the washout of solute in the renal medulla may be induced as a response to increased perfusion pressure and elevated circulating angiotensin.", "contents": "Studies on intrarenal prostaglandins. Effect of unilateral renal artery constriction on lipid droplets in the medullary interstitial cells of the 'opposite' kidney in rabbits. The unilateral renal artery in rabbits was constricted, and lipid droplet count in the medullary interstitial cells of the 'opposite' kidney was performed 1 week after surgery. Lipid droplet count in hypertensive rabbits was less than that in both nonhypertensive and normal rabbits and was inversely proportional to the mean blood pressure. Lipid droplet count was significantly correlated with the juxtaglomerular granulation index and the sodium content in the inner medulla. The present results suggest that, in the opposite kidney of rabbits hypertensive due to unilateral constriction of the renal artery, the enhanced release of prostaglandins and the washout of solute in the renal medulla may be induced as a response to increased perfusion pressure and elevated circulating angiotensin."}
{"id": "PMID:218329", "title": "[Effect of dichloroethane on the hydroxylating and conjugating activity of the membranes of the cytoplasmic network of liver tissue].", "content": "The hydroxylating and conjugating activities of the cytoplasmic network membranes in the rat liver tissues were studied as affected by dichloroethane. Administration of this substance decreases the monooxygenase and uridine diphosphate glucuronyl transferase activities in the tissue under study. The reduced content of cytochrome P450 is the earliest index of a decrease in the hydroxylating activity of the liver tissue. This fall in the hydroxylating and conjugating activity in the cytoplasmic network membranes of the liver tissues testifies to the fact that the intensity of the metabolism and detoxication of certain foreign substances in this organ under the effect of dichlorethane is reduced.", "contents": "[Effect of dichloroethane on the hydroxylating and conjugating activity of the membranes of the cytoplasmic network of liver tissue]. The hydroxylating and conjugating activities of the cytoplasmic network membranes in the rat liver tissues were studied as affected by dichloroethane. Administration of this substance decreases the monooxygenase and uridine diphosphate glucuronyl transferase activities in the tissue under study. The reduced content of cytochrome P450 is the earliest index of a decrease in the hydroxylating activity of the liver tissue. This fall in the hydroxylating and conjugating activity in the cytoplasmic network membranes of the liver tissues testifies to the fact that the intensity of the metabolism and detoxication of certain foreign substances in this organ under the effect of dichlorethane is reduced."}
{"id": "PMID:218333", "title": "[Biological characteristics of the plaque variants of the swine vesicular disease virus].", "content": "The Swine Vesicular Disease virus yields a heterogenic plaque population consisting of large round plaques of 8-10 mm, small uniform plaques with slightly indented contours, measuring 1-3 mm, and single plaques of transient form and size. The reisolates of the large (Lpf) plaques give a population that is similar to the initial virus, while the cloning of the small (Mpf) plaques leads to a homogenic population of such plaques. In vivo, the virus of the large plaques manifests enhanced virulence for swine. On the other hand, the selected small-plaque variant is apathogenic, which makes it possible to produce a live avirulent vaccine.", "contents": "[Biological characteristics of the plaque variants of the swine vesicular disease virus]. The Swine Vesicular Disease virus yields a heterogenic plaque population consisting of large round plaques of 8-10 mm, small uniform plaques with slightly indented contours, measuring 1-3 mm, and single plaques of transient form and size. The reisolates of the large (Lpf) plaques give a population that is similar to the initial virus, while the cloning of the small (Mpf) plaques leads to a homogenic population of such plaques. In vivo, the virus of the large plaques manifests enhanced virulence for swine. On the other hand, the selected small-plaque variant is apathogenic, which makes it possible to produce a live avirulent vaccine."}
{"id": "PMID:218330", "title": "[Properties of 3':5'-AMP- and 3':5'-GMP-phosphodiesterases in the retina].", "content": "The activity of 3':5'-AMP and 3':5'-GMP phosphodiesterase was determined in retina of some animals. In all cases the enzymic activity with the presence of 3':5'-GMP is higher than with utilization of 3':5'-AMP. About 60% of the enzyme activity with 3':5' GMP as a substrate is lost in the process of obtaining the outer segments extracted from the bovine retina. The enzyme activity was completely detected with 3':5' AMP as a substrate. The both enzymes are equally extracted from the photoreceptory membranes by a weak ionic buffer. Differences are found in the stability of 3':5'-AMP and 3':5-GMP-phosphodiesterase during storage. The form of the enzyme splitting 3':5'-GMP is more unstable.", "contents": "[Properties of 3':5'-AMP- and 3':5'-GMP-phosphodiesterases in the retina]. The activity of 3':5'-AMP and 3':5'-GMP phosphodiesterase was determined in retina of some animals. In all cases the enzymic activity with the presence of 3':5'-GMP is higher than with utilization of 3':5'-AMP. About 60% of the enzyme activity with 3':5' GMP as a substrate is lost in the process of obtaining the outer segments extracted from the bovine retina. The enzyme activity was completely detected with 3':5' AMP as a substrate. The both enzymes are equally extracted from the photoreceptory membranes by a weak ionic buffer. Differences are found in the stability of 3':5'-AMP and 3':5-GMP-phosphodiesterase during storage. The form of the enzyme splitting 3':5'-GMP is more unstable."}
{"id": "PMID:218334", "title": "[Micromethod of determining the complement-binding properties of commercial series of the foot-and-mouth disease virus].", "content": "Investigations were carried out to establish the possibility of using a micromethod of the complement-fixation test to determine the complement-fixing properties of productional series of the foot-and-mouth disease virus. It was found that the micromethod referred to is an economically profitable and practically simple one. It is readily applicable requiring no particular apparatuses and equipment, is specific, and can successfully be used instead of the routinely employed CFT method. The micromethod suggested is economical, requiring minimal amounts (0.025 cu.c7) of the components taking part.", "contents": "[Micromethod of determining the complement-binding properties of commercial series of the foot-and-mouth disease virus]. Investigations were carried out to establish the possibility of using a micromethod of the complement-fixation test to determine the complement-fixing properties of productional series of the foot-and-mouth disease virus. It was found that the micromethod referred to is an economically profitable and practically simple one. It is readily applicable requiring no particular apparatuses and equipment, is specific, and can successfully be used instead of the routinely employed CFT method. The micromethod suggested is economical, requiring minimal amounts (0.025 cu.c7) of the components taking part."}
{"id": "PMID:218336", "title": "Giant cell tumor of bone. Variations in patterns of appearance of different cell types.", "content": "Eleven benign giant cell tumors of bone were studied in the electron microscope, and the fine structural localization of acid phosphatase was elucidated. Three distinct cell types are always present in these tumors: stromal cells type 1; stromal cells type 2; and multinucleated giant cells. Small mononuclear cells may also occur, but are not likely to be actively participating in the neoplastic process. The range of variability in the fine structure of the different cell types constituting this tumor has been established. Variations in appearances include: a) presence of nuclear pseudoinclusions in stromal cells type 1 and multinucleated giant cells; b) aberrations in the structure of the rough surfaced endoplasmic reticulum in the same cell types; c) occurrence of ruffled borders, ectoplasmic layers and cytoplasmic labyrinths containing acid phosphatase in the giant cells. Some giant cells show evidence of marked phagocytic activity and contain large and numerous residual bodies carrying acid phosphatase. The significance of the interrelations between the different cell types are discussed and the possible role of stromal cells type 2 in immunological mechanisms directed against the tumor cells are mentioned.", "contents": "Giant cell tumor of bone. Variations in patterns of appearance of different cell types. Eleven benign giant cell tumors of bone were studied in the electron microscope, and the fine structural localization of acid phosphatase was elucidated. Three distinct cell types are always present in these tumors: stromal cells type 1; stromal cells type 2; and multinucleated giant cells. Small mononuclear cells may also occur, but are not likely to be actively participating in the neoplastic process. The range of variability in the fine structure of the different cell types constituting this tumor has been established. Variations in appearances include: a) presence of nuclear pseudoinclusions in stromal cells type 1 and multinucleated giant cells; b) aberrations in the structure of the rough surfaced endoplasmic reticulum in the same cell types; c) occurrence of ruffled borders, ectoplasmic layers and cytoplasmic labyrinths containing acid phosphatase in the giant cells. Some giant cells show evidence of marked phagocytic activity and contain large and numerous residual bodies carrying acid phosphatase. The significance of the interrelations between the different cell types are discussed and the possible role of stromal cells type 2 in immunological mechanisms directed against the tumor cells are mentioned."}
{"id": "PMID:218337", "title": "Pituitary adenoma, primary parathyroid hyperplasia and papillary (non-medullary) thyroid carcinoma. A case of multiple endocrine neoplasia (MEN).", "content": "An acidophilic pituitary adenoma associated with primary nodular parathyroid hyperplasia and a small papillary thyroid carcinoma was discovered at the autopsy of a 44 year old female acromegalic. The thyroid carcinoma showed evidence of lymphatic spread. Several etiopathogenetic mechanisms for the non-medullary thyroid carcinomata associated with Multiple Endocrine Neoplasia (MEN) have been postulated, since the follicular epithelium of the thyroid does not belong to the neural ectoderm derivates unlike the C-cells of the thyroid, the adenohypophysis and probably the parathyroid glands. Apart from genetic influence, or coincidence, one has to rule out carcinogenic exposure or hormonal influence. Clinically speaking, one should always consider whether malignant thyroid disease coexists with hyperplastic or neoplastic parathyroid tissue.", "contents": "Pituitary adenoma, primary parathyroid hyperplasia and papillary (non-medullary) thyroid carcinoma. A case of multiple endocrine neoplasia (MEN). An acidophilic pituitary adenoma associated with primary nodular parathyroid hyperplasia and a small papillary thyroid carcinoma was discovered at the autopsy of a 44 year old female acromegalic. The thyroid carcinoma showed evidence of lymphatic spread. Several etiopathogenetic mechanisms for the non-medullary thyroid carcinomata associated with Multiple Endocrine Neoplasia (MEN) have been postulated, since the follicular epithelium of the thyroid does not belong to the neural ectoderm derivates unlike the C-cells of the thyroid, the adenohypophysis and probably the parathyroid glands. Apart from genetic influence, or coincidence, one has to rule out carcinogenic exposure or hormonal influence. Clinically speaking, one should always consider whether malignant thyroid disease coexists with hyperplastic or neoplastic parathyroid tissue."}
{"id": "PMID:218363", "title": "[Proliferation of hamster embryo fibroblast cultures infected with the herpes simplex virus].", "content": "In the HEF system in logarythmic and stationary phases of the culture growth the type-2 herpes simplex virus serves as a stimulator of proliferative processes in the cell (there is an increase of the labelled cells index, mitotic index and the intensity of labelling). The capacity of herpes virus not to suppress the cell DNA synthesis, as infestious viruses do, but to stimulate poliferative abilities of the cell indicates a presumable potential oncogenicity of this virus.", "contents": "[Proliferation of hamster embryo fibroblast cultures infected with the herpes simplex virus]. In the HEF system in logarythmic and stationary phases of the culture growth the type-2 herpes simplex virus serves as a stimulator of proliferative processes in the cell (there is an increase of the labelled cells index, mitotic index and the intensity of labelling). The capacity of herpes virus not to suppress the cell DNA synthesis, as infestious viruses do, but to stimulate poliferative abilities of the cell indicates a presumable potential oncogenicity of this virus."}
{"id": "PMID:218361", "title": "[Inhibitory effect of cerebrospinal fluid on the activity of sodium-, potassium-ATPase in animal brain synaptic membranes].", "content": "Liquor cerebrospinalis, obtained from patients with various diseases, inhibited Na, K-ATPase from rat and bovine synaptic membranes and did not influence on the activity of Mg-ATPase. The inhibition was independent on the type of disease. The inhibitory effect of liquor cerebrospinalis disappeared after dyalisis of it against Krebs-Ringer solution. Liquor cerebrospinalis appears to contain an endogenous inhibitor of synaptic Na,K-ATPase, which controls the enzymatic activity in vivo.", "contents": "[Inhibitory effect of cerebrospinal fluid on the activity of sodium-, potassium-ATPase in animal brain synaptic membranes]. Liquor cerebrospinalis, obtained from patients with various diseases, inhibited Na, K-ATPase from rat and bovine synaptic membranes and did not influence on the activity of Mg-ATPase. The inhibition was independent on the type of disease. The inhibitory effect of liquor cerebrospinalis disappeared after dyalisis of it against Krebs-Ringer solution. Liquor cerebrospinalis appears to contain an endogenous inhibitor of synaptic Na,K-ATPase, which controls the enzymatic activity in vivo."}
{"id": "PMID:218368", "title": "[Three decades' experience in the treatment of bronchogenic carcinoma by pulmonary resection (author's transl)].", "content": "A review of the development of thoracic surgery is followed by a description of the results obtained by us in the surgical treatment of bronchogenic carcinoma from the difficult beginnings in 1947 up to the present day. The diagnostic investigations, indications for operation and the operative risks are discussed on the basis of 1532 pulmonary resections. The subsequent fate of this patients is known to us almost without exception over a period of three decades. Diagrams show the ten-year survival rates. The importance of early diagnosis and the priority of surgical treatment are two basic conclusions which still hold true today.", "contents": "[Three decades' experience in the treatment of bronchogenic carcinoma by pulmonary resection (author's transl)]. A review of the development of thoracic surgery is followed by a description of the results obtained by us in the surgical treatment of bronchogenic carcinoma from the difficult beginnings in 1947 up to the present day. The diagnostic investigations, indications for operation and the operative risks are discussed on the basis of 1532 pulmonary resections. The subsequent fate of this patients is known to us almost without exception over a period of three decades. Diagrams show the ten-year survival rates. The importance of early diagnosis and the priority of surgical treatment are two basic conclusions which still hold true today."}
{"id": "PMID:218372", "title": "[The role of the adenohypophysis in connection with changes in the thyroid caused by old age (author's transl)].", "content": "The findings indicate that changes caused by old age in the mechanism of the TSH action on the thyroid occur in the phases which are connected with the storage of adenosine triphosphate. That leads one to assume that changes caused by old age in the thyroid responsiveness to the action of TSH are probably conditioned by the following phenomena: 1. the decrease in the receptors \"pro tropes\" hormone and/or the disturbance of the correlations between TSH and the receptor 2. disturbance of the activity of the adenylocyclase 3. the phospho-diesterase activation.", "contents": "[The role of the adenohypophysis in connection with changes in the thyroid caused by old age (author's transl)]. The findings indicate that changes caused by old age in the mechanism of the TSH action on the thyroid occur in the phases which are connected with the storage of adenosine triphosphate. That leads one to assume that changes caused by old age in the thyroid responsiveness to the action of TSH are probably conditioned by the following phenomena: 1. the decrease in the receptors \"pro tropes\" hormone and/or the disturbance of the correlations between TSH and the receptor 2. disturbance of the activity of the adenylocyclase 3. the phospho-diesterase activation."}
{"id": "PMID:218373", "title": "Cooperative pathway induction of T lymphocyte mitogen stimulation.", "content": "Isolated peritoneal mouse macrophages pretreated with the mitogenic enzyme combination neuraminidase (EC 3.2.1.18) plus galactose oxidase (EC 1.1.3.9.) (NAGO), or with NaIO4, stimulate macrophage-depleted lymphocytes mitogenically by a macrophage-derived signal, different from the originally used mitogen. Polyethylene glycol (PEG) treatment of the cultures, although itself nonmitogenic, strongly enhances the mitogenic response of the lymphocytes. Under culture conditions the macrophage-derived signal is transmitted to lymphocytes by direct cell contact, a finding which explains the need of a critical cell density for T lymphocyte stimulation. In the absence of macrophages, lysates from mitogen-preteated macrophages stimulate column-purified lymphocytes in the presence of PEG. Our results indicate that mitogenic activation of lymphocytes is mediated through two sequential triggering events, induction (by mitogen treatment) of a macrophage-derived signal and commitment (by nonmitogenic PEG treatment) of lymphocytes to react to the signal. Reconstitution of the mitogenic response can be achieved by a sequential induction of both these events.", "contents": "Cooperative pathway induction of T lymphocyte mitogen stimulation. Isolated peritoneal mouse macrophages pretreated with the mitogenic enzyme combination neuraminidase (EC 3.2.1.18) plus galactose oxidase (EC 1.1.3.9.) (NAGO), or with NaIO4, stimulate macrophage-depleted lymphocytes mitogenically by a macrophage-derived signal, different from the originally used mitogen. Polyethylene glycol (PEG) treatment of the cultures, although itself nonmitogenic, strongly enhances the mitogenic response of the lymphocytes. Under culture conditions the macrophage-derived signal is transmitted to lymphocytes by direct cell contact, a finding which explains the need of a critical cell density for T lymphocyte stimulation. In the absence of macrophages, lysates from mitogen-preteated macrophages stimulate column-purified lymphocytes in the presence of PEG. Our results indicate that mitogenic activation of lymphocytes is mediated through two sequential triggering events, induction (by mitogen treatment) of a macrophage-derived signal and commitment (by nonmitogenic PEG treatment) of lymphocytes to react to the signal. Reconstitution of the mitogenic response can be achieved by a sequential induction of both these events."}
{"id": "PMID:218374", "title": "Depressed prostaglandin release from peritoneal cells induced by a T cell adjuvant, lentinan.", "content": "PGE and PGF release from peritoneal exudate cells was studied in mice after injection with two beta (1-3) glucans, the antitumor active lentinan and the inactive pachyman, 4 days after injection of both polysaccharides, the spontaneous and phagocytosis-induced PGE and PGF release was markedly suppressed. However, only the immunopotentiator lentinan induced peritoneal exudate cells which exhibited a longer lasting diminished PG release. The data suggest that the T cell adjuvant lentinan may potentiate cellular immune responses by reducing synthesis of immune suppressive prostaglandins from peritoneal exudate cells.", "contents": "Depressed prostaglandin release from peritoneal cells induced by a T cell adjuvant, lentinan. PGE and PGF release from peritoneal exudate cells was studied in mice after injection with two beta (1-3) glucans, the antitumor active lentinan and the inactive pachyman, 4 days after injection of both polysaccharides, the spontaneous and phagocytosis-induced PGE and PGF release was markedly suppressed. However, only the immunopotentiator lentinan induced peritoneal exudate cells which exhibited a longer lasting diminished PG release. The data suggest that the T cell adjuvant lentinan may potentiate cellular immune responses by reducing synthesis of immune suppressive prostaglandins from peritoneal exudate cells."}
{"id": "PMID:218375", "title": "[Spasm of the adductor muscles, pre-dislocation and dislocations of the hip joints in children and adolescents with cerebral palsy. Clinical observations on aetiology, pathogenesis, therapy and rehabilitation. Part I: The effect of open myotenotomy of the gracilis muscle and of the long and short adductor muscles in connection with total extrapelvine resection of the obturator nerve, on the hip joints and static function (author's transl)].", "content": "Spasm and contraction of the adductor muscles involve, on the one hand, danger in respect of the development of a dislocation of the hip, and are a serious impediment to a walking ability on the other. Hence, surgery is often necessary. The article reports on the results of consequent weakening of the adductor muscles as a result of open myotenotomy in association with complete extrapelvine resection of the obturator nerve. 27 patients were subjected to surgery--in most cases bilaterally--at an age between 2 years and 5 months and 18 years, with a follow-up period of up to 15 years. The study does not include patients with spastic dislocation of the hip in whom this method was applied on the non-dislocated side and on the dislocated side in combination with iliopsoas tenotomy. This method makes it possible to achieve regression of existing defective positions of the hip joints. In a few cases, the valgus position of the neck of the femur was corrected to some extent. In two patients it was not possible to prevent the progress of a developing dislocation of the hip. These results show that, whereas the adductor muscles represent an essential factor for the occurrence of a spastic dislocation of the hip, other forces are most probably also involved. In the majority of cases, results were favourable in respect of the static function, although in some cases the success became evident after several years only, especially in mentally retarded patients and in apathetic individuals. Important for therapeutic success is the follow-up. The principles of its therapy are thoroughly discussed. Surgery is indicated only in special cases. Indications must be observed very strictly, since the risk of excessive weakening of the adductor muscles should not be underestimated.", "contents": "[Spasm of the adductor muscles, pre-dislocation and dislocations of the hip joints in children and adolescents with cerebral palsy. Clinical observations on aetiology, pathogenesis, therapy and rehabilitation. Part I: The effect of open myotenotomy of the gracilis muscle and of the long and short adductor muscles in connection with total extrapelvine resection of the obturator nerve, on the hip joints and static function (author's transl)]. Spasm and contraction of the adductor muscles involve, on the one hand, danger in respect of the development of a dislocation of the hip, and are a serious impediment to a walking ability on the other. Hence, surgery is often necessary. The article reports on the results of consequent weakening of the adductor muscles as a result of open myotenotomy in association with complete extrapelvine resection of the obturator nerve. 27 patients were subjected to surgery--in most cases bilaterally--at an age between 2 years and 5 months and 18 years, with a follow-up period of up to 15 years. The study does not include patients with spastic dislocation of the hip in whom this method was applied on the non-dislocated side and on the dislocated side in combination with iliopsoas tenotomy. This method makes it possible to achieve regression of existing defective positions of the hip joints. In a few cases, the valgus position of the neck of the femur was corrected to some extent. In two patients it was not possible to prevent the progress of a developing dislocation of the hip. These results show that, whereas the adductor muscles represent an essential factor for the occurrence of a spastic dislocation of the hip, other forces are most probably also involved. In the majority of cases, results were favourable in respect of the static function, although in some cases the success became evident after several years only, especially in mentally retarded patients and in apathetic individuals. Important for therapeutic success is the follow-up. The principles of its therapy are thoroughly discussed. Surgery is indicated only in special cases. Indications must be observed very strictly, since the risk of excessive weakening of the adductor muscles should not be underestimated."}
{"id": "PMID:218397", "title": "[Suicide risk and care of suicide attempters].", "content": "Starting from the notion of suicidal risk and a critique of its usage, it is possible to distinguish groups whose suicidal risk is particularly high. The suicidal group-composed of persons who have already attempted to commit suicide once-is in this paper the subject of general considerations as well as personal research. The latter shows that it is still difficult to detect those persons who are about to commit suicide and that tell-tale signs-be they clinical or resulting from tests-are still not very reliable. The difficulties encountered by secondary prevention are made obvious by two pieces of research done on the taking in charge of suicide-prone persons in a university general hospital. the timely recognition of the pre-suicidal syndrome and of the self-denial syndrome is very important for suicide prevention. Self-depreciation, and consequently the narcissistic blow is, as are the aggression phenomena, one of the psychological cores which lead to an act of suicide. Medical attitudes concerning the suicidal person are analyzed, and the difficulty in the psychotherapeutic relationship is stressed. Pratical considerations on the psychotherapeutic approach to the suicidal person close up the article.", "contents": "[Suicide risk and care of suicide attempters]. Starting from the notion of suicidal risk and a critique of its usage, it is possible to distinguish groups whose suicidal risk is particularly high. The suicidal group-composed of persons who have already attempted to commit suicide once-is in this paper the subject of general considerations as well as personal research. The latter shows that it is still difficult to detect those persons who are about to commit suicide and that tell-tale signs-be they clinical or resulting from tests-are still not very reliable. The difficulties encountered by secondary prevention are made obvious by two pieces of research done on the taking in charge of suicide-prone persons in a university general hospital. the timely recognition of the pre-suicidal syndrome and of the self-denial syndrome is very important for suicide prevention. Self-depreciation, and consequently the narcissistic blow is, as are the aggression phenomena, one of the psychological cores which lead to an act of suicide. Medical attitudes concerning the suicidal person are analyzed, and the difficulty in the psychotherapeutic relationship is stressed. Pratical considerations on the psychotherapeutic approach to the suicidal person close up the article."}
{"id": "PMID:218400", "title": "Comparison of Fusobacterium sp. versus Bacteroides sp. in the monoxenic cultivation of E. histolytica.", "content": "By means of the performed studies it was established that 6 Fusobacteria strains enhanced the growth of E. histolytica while 4 Bacteroides strains did not possess this property.", "contents": "Comparison of Fusobacterium sp. versus Bacteroides sp. in the monoxenic cultivation of E. histolytica. By means of the performed studies it was established that 6 Fusobacteria strains enhanced the growth of E. histolytica while 4 Bacteroides strains did not possess this property."}
{"id": "PMID:218402", "title": "[Electron microscopic study of several features of spore formation in type B Clostridium perfringens].", "content": "The authors carried out electron microscopy of the thin sections of Cl. perfringens, type B (strain No. 89). Material of middle electron density was revealed on the cell wall surface from the first hours of the culture growing; the cytoplasm displayed both rod-like incorporations with transverse striations, and phage particles. Different spore formation disturbances were revealed in the strain under study. In the majority of cells spore formation was blocked at the III--V stage. Besides, there were pseudospores, whereas mature spores were rarely encountered, and even those which did occur, were at the stage of growing.", "contents": "[Electron microscopic study of several features of spore formation in type B Clostridium perfringens]. The authors carried out electron microscopy of the thin sections of Cl. perfringens, type B (strain No. 89). Material of middle electron density was revealed on the cell wall surface from the first hours of the culture growing; the cytoplasm displayed both rod-like incorporations with transverse striations, and phage particles. Different spore formation disturbances were revealed in the strain under study. In the majority of cells spore formation was blocked at the III--V stage. Besides, there were pseudospores, whereas mature spores were rarely encountered, and even those which did occur, were at the stage of growing."}
{"id": "PMID:218403", "title": "[Effect of small doses of diphtheria exotoxin on cell cultures].", "content": "High diphtheria exotoxin concentrations induced irreversible injuries to all the cultures under study (L, HeLa, spcv pzM). However, its final titres in the mentioned cells differed. HeLa and pzM cells, being highly sensitive, can be recommended for titration of dipheria exotoxin, instead of the expensive guinea pig tests. Low (subtoxic) doses produced cytoproliferative action and caused changes of the cell properties.", "contents": "[Effect of small doses of diphtheria exotoxin on cell cultures]. High diphtheria exotoxin concentrations induced irreversible injuries to all the cultures under study (L, HeLa, spcv pzM). However, its final titres in the mentioned cells differed. HeLa and pzM cells, being highly sensitive, can be recommended for titration of dipheria exotoxin, instead of the expensive guinea pig tests. Low (subtoxic) doses produced cytoproliferative action and caused changes of the cell properties."}
{"id": "PMID:218404", "title": "[Action of cyclic adenosine monophosphate on the spleen antibody--forming cells of rabbits immunized with Escherichia coli].", "content": "Cyclic adenosine monophosphate (cAMP) parenterally injected to rabbits (immunized intraperitoneally with thymus-independent antigen of killed E. coli 0127/545) during January--April inhibited production of antibody-forming cells (AFC) in the spleen of these animals, and during May--June it increased the AFC count. Both the stimulating and inhibitory effect of cAMP was associated with the administration of the same doses of 25--250 microgram/kg. The nature of the cAMP effect on the production of the AFC depends on the initial immune response level. At the maximum immune response and in the absence of the dose-effect dependence cAMP inhibited the antibody formation, but when the immunological reaction was below the maximal level and in the presence of the dose-effect relationship cAMP increased the AFC production.", "contents": "[Action of cyclic adenosine monophosphate on the spleen antibody--forming cells of rabbits immunized with Escherichia coli]. Cyclic adenosine monophosphate (cAMP) parenterally injected to rabbits (immunized intraperitoneally with thymus-independent antigen of killed E. coli 0127/545) during January--April inhibited production of antibody-forming cells (AFC) in the spleen of these animals, and during May--June it increased the AFC count. Both the stimulating and inhibitory effect of cAMP was associated with the administration of the same doses of 25--250 microgram/kg. The nature of the cAMP effect on the production of the AFC depends on the initial immune response level. At the maximum immune response and in the absence of the dose-effect dependence cAMP inhibited the antibody formation, but when the immunological reaction was below the maximal level and in the presence of the dose-effect relationship cAMP increased the AFC production."}
{"id": "PMID:218405", "title": "[Clinical immunological characteristics of herpes zoster].", "content": "Changes of antibody formation of 96 patients with various clinical forms of herpes zoster were traced by indirect hemagglutination inhibition test. Four variants of the immunological response were distinguished; clinical characteristics of each of these groups is presented. The initial antibody level failed to determine the severity of the course of the disease in herpes zoster.", "contents": "[Clinical immunological characteristics of herpes zoster]. Changes of antibody formation of 96 patients with various clinical forms of herpes zoster were traced by indirect hemagglutination inhibition test. Four variants of the immunological response were distinguished; clinical characteristics of each of these groups is presented. The initial antibody level failed to determine the severity of the course of the disease in herpes zoster."}
{"id": "PMID:218406", "title": "[Comparative study of the smallpox vaccines from B-51, EM-63 and L-IVP in a controlled epidemiological experiment. II. The characteristiics of the immunogenicity of the smallpox vaccines].", "content": "Immunogenicity of smallpox vaccines prepared of EM-63, L-IVP, and B-51 strains was studied under conditions of strict controlled epidemiological trial. Skin reactions to revaccination and vaccines antigenic activity indices were detemined in the persons vaccinated. Changes in the virus-neutralizing and antibodies suppressing hemagglutination was the same in persons vaccinated with any of the preparations tested. The maximal virus-neutralizing antibodies level was determined 1 month after the vaccination and persisted without any essential changes for one year. The titre of hemagglutination inhibiting antibodies also reached the maximum in one month, but diminished gradually by the end of one year after the vaccination. There were found no significant differences in the antigenic activity of the vaccines. The vaccines studied also displayed no difference in the number and character of skin reactions to revaccination. In comparing the antibodies level and the character of skin reactions to revaccination it was found that the titres of hemagglutination inhibiting antibodies and virus-neutralizing antibodies of 1:40 and over were in the great majority of cases determined in the blood sera of the vaccinated persons with the immediate and negative reactions to revaccination, i. e. in those with intensive postvaccinal immunity.", "contents": "[Comparative study of the smallpox vaccines from B-51, EM-63 and L-IVP in a controlled epidemiological experiment. II. The characteristiics of the immunogenicity of the smallpox vaccines]. Immunogenicity of smallpox vaccines prepared of EM-63, L-IVP, and B-51 strains was studied under conditions of strict controlled epidemiological trial. Skin reactions to revaccination and vaccines antigenic activity indices were detemined in the persons vaccinated. Changes in the virus-neutralizing and antibodies suppressing hemagglutination was the same in persons vaccinated with any of the preparations tested. The maximal virus-neutralizing antibodies level was determined 1 month after the vaccination and persisted without any essential changes for one year. The titre of hemagglutination inhibiting antibodies also reached the maximum in one month, but diminished gradually by the end of one year after the vaccination. There were found no significant differences in the antigenic activity of the vaccines. The vaccines studied also displayed no difference in the number and character of skin reactions to revaccination. In comparing the antibodies level and the character of skin reactions to revaccination it was found that the titres of hemagglutination inhibiting antibodies and virus-neutralizing antibodies of 1:40 and over were in the great majority of cases determined in the blood sera of the vaccinated persons with the immediate and negative reactions to revaccination, i. e. in those with intensive postvaccinal immunity."}
{"id": "PMID:218407", "title": "[Nonspecific means of increasing the sensitivity of the passive hemagglutination reaction].", "content": "The effect of some methods of preliminary treatment of erythrocytes on the PHAT depended on the sensitin n\u00e1ture and the method of erythrocyte load. In case of erythrocyte load with nonprotein and immunoglobulin sensitins without any conjugating agents the simulating effect of heating and periodate treatment was caused not by increase of stable sensitin binding, but by the reduction of physico-chemical resistance of erythrocytes. This effect of erythrocyte treatment permitted to increase the sensitivity of the antibodies and antigens determination. In loading the erythrocytes with the aid of conjugating agents and in sensitization with protein antigens after Boyden no stimuating effect of the treatment was noted.", "contents": "[Nonspecific means of increasing the sensitivity of the passive hemagglutination reaction]. The effect of some methods of preliminary treatment of erythrocytes on the PHAT depended on the sensitin n\u00e1ture and the method of erythrocyte load. In case of erythrocyte load with nonprotein and immunoglobulin sensitins without any conjugating agents the simulating effect of heating and periodate treatment was caused not by increase of stable sensitin binding, but by the reduction of physico-chemical resistance of erythrocytes. This effect of erythrocyte treatment permitted to increase the sensitivity of the antibodies and antigens determination. In loading the erythrocytes with the aid of conjugating agents and in sensitization with protein antigens after Boyden no stimuating effect of the treatment was noted."}
{"id": "PMID:218408", "title": "[Course of the hypertensive syndrome in spongioblastoma multiforme].", "content": "Of 140 patients with brain tumors of a supratentorial localization, in 50 cases a multiform spongioblastoma was established; it was verified either by a surgical operation, or during section. Three variants of the hypertensive syndrome were distinguished: tumorous, pseudovascular, pseudoinflammatory. The morphological brain studies determined an expressed vascular and cellular reaction to the malignant tumorous process. In a pseudoinflammatory clinical variant inflammatory changes were more expressed, while in pseudovascular--vascular changes. An atypical clinical development of multiform spongioblastoma is determined by the localization of the tumor, its histological structure, infiltrating growth and intoxication stemming from the tumor.", "contents": "[Course of the hypertensive syndrome in spongioblastoma multiforme]. Of 140 patients with brain tumors of a supratentorial localization, in 50 cases a multiform spongioblastoma was established; it was verified either by a surgical operation, or during section. Three variants of the hypertensive syndrome were distinguished: tumorous, pseudovascular, pseudoinflammatory. The morphological brain studies determined an expressed vascular and cellular reaction to the malignant tumorous process. In a pseudoinflammatory clinical variant inflammatory changes were more expressed, while in pseudovascular--vascular changes. An atypical clinical development of multiform spongioblastoma is determined by the localization of the tumor, its histological structure, infiltrating growth and intoxication stemming from the tumor."}
{"id": "PMID:218409", "title": "[Study of muscle excitability in response to currents of different duration in the diagnosis of nerve injuries].", "content": "The \"strength-duration\" curve was studied in 154 patients in different periods after injury to the median nerve, ulnar nerve or both nerves. The most probable mean values of strength (U) in changes of the duration (t) of the current 1--6, 7--11 months and more than 12 months after injury were obtained by means of the equation U=a0 + a1t +a2t2 by the least squares method. It was established that the excitability of muscles diminishes continuously but persists more than 15 years after total anatomical interruption of the nerve. Absence of electroexcitability of the forearm muscles as a result of ischemia is not a contraindication for nerve suturation. Suturation of the nerve leads to restoration of sensibility and active contractions of the hand muscles. The deviations in the \"strength-duration\" curve are signs of partial injury to the nerve. It was found that the more the number of deviations in the \"strength-duration\" curve and the more its left part on the side of the injury resembles the curve recorded from the symmetrical healthy muscle, the more rapidly is the nerve conduction restored and the more rapidly it improves after nonoperative treatment.", "contents": "[Study of muscle excitability in response to currents of different duration in the diagnosis of nerve injuries]. The \"strength-duration\" curve was studied in 154 patients in different periods after injury to the median nerve, ulnar nerve or both nerves. The most probable mean values of strength (U) in changes of the duration (t) of the current 1--6, 7--11 months and more than 12 months after injury were obtained by means of the equation U=a0 + a1t +a2t2 by the least squares method. It was established that the excitability of muscles diminishes continuously but persists more than 15 years after total anatomical interruption of the nerve. Absence of electroexcitability of the forearm muscles as a result of ischemia is not a contraindication for nerve suturation. Suturation of the nerve leads to restoration of sensibility and active contractions of the hand muscles. The deviations in the \"strength-duration\" curve are signs of partial injury to the nerve. It was found that the more the number of deviations in the \"strength-duration\" curve and the more its left part on the side of the injury resembles the curve recorded from the symmetrical healthy muscle, the more rapidly is the nerve conduction restored and the more rapidly it improves after nonoperative treatment."}
{"id": "PMID:218410", "title": "Kinetic studies of the interaction of uranyl ions with inorganic pyrophosphatase from baker's yeast.", "content": "Kinetic measurements were performed to test the effect of uranyl ions on the enzymatic hydrolysis of pyrophosphate. A strong inhibition of the enzyme was found. From a Dixon-plot an inhibition competitive to the substrate magnesium pyrophosphate and an inhibitory constant of Ki = 3 . 10(-7) M was deduced.", "contents": "Kinetic studies of the interaction of uranyl ions with inorganic pyrophosphatase from baker's yeast. Kinetic measurements were performed to test the effect of uranyl ions on the enzymatic hydrolysis of pyrophosphate. A strong inhibition of the enzyme was found. From a Dixon-plot an inhibition competitive to the substrate magnesium pyrophosphate and an inhibitory constant of Ki = 3 . 10(-7) M was deduced."}
{"id": "PMID:218412", "title": "Varicose veins in congenital angiodysplasias.", "content": "Three cases of Klippel--Trenaunay--Weber's syndrome are presented. The syndrome is characterized by cutaneous hemangioma, hypertrophy of an extremity and varicose veins. It is combined with angiodysplasias, either in the form of aplasia/hypoplasia of deep veins and/or in the form of arteriovenous shunts. The varicose veins will frequently be the dominant symptom, and it is emphasized that surgical treatment should not be instituted until the patient has been examined angiographically, with both phlebography and arteriography. The methods and the classification are discussed and the possibilities of treatment are outlined.", "contents": "Varicose veins in congenital angiodysplasias. Three cases of Klippel--Trenaunay--Weber's syndrome are presented. The syndrome is characterized by cutaneous hemangioma, hypertrophy of an extremity and varicose veins. It is combined with angiodysplasias, either in the form of aplasia/hypoplasia of deep veins and/or in the form of arteriovenous shunts. The varicose veins will frequently be the dominant symptom, and it is emphasized that surgical treatment should not be instituted until the patient has been examined angiographically, with both phlebography and arteriography. The methods and the classification are discussed and the possibilities of treatment are outlined."}
{"id": "PMID:218413", "title": "Tissue culture studies on human pituitary tumours: long term release of anterior pituitary hormones into the culture medium.", "content": "A study was undertaken to determine the length of time that human pituitary tumours are capable of releasing anterior pituitary polypeptide hormones in vitro under basal conditions and to study the spectrum of hormone release by functioning and \"non-functioning\" pituitary neoplasms. Fragments from the pituitary tumours of 10 patients in the following categories: 1 Cushing's disease, 2 with amenorrhoea-galactorrhoea, 3 with acromegaly, and 4 with \"non-functioning\" pituitary tumours and from 2 normal human anterior pituitary glands were placed in primary culture immediately after surgery. The in vitro release of human growth hormone (hGH), prolactin (Prl), thyrotrophin (TSH), adrenocorticotrophin (ACTH), luteinizing hormone (LH), and follicle stimulating hormone (FSH) was measured by specific radioimmunoassays at the end of each week in culture. Hormone release was surveyed from 6 weeks to 6 months depending upon the survival of the culture. Hormone release patterns were compared with clinical and pathological data. In the initial week of the study, all 6 anterior pituitary polypeptides were detected in the media from the 2 control pituitaries and from 4 of the tumours (1 amenorrhoea-galactorrhoea and 3 acromegaly) in concentrations up to 100 ng/ml of medium while 5 of the 6 hormones were readily detectable in the media from 2 additional tumour samples (Cushing's disease and 1 \"non-functioning\" pituitary tumour). The media of the remaining 4 tumours contained at least 3 of the 6 hormones (1 amenorrhoea-galactorrhoea and 3 \"non-functioning\" pituitary tumours). After 6 months in culture, the 6 hormones were readily detectable in at least 1 of the 5 surviving cultures and hGH (up to 800 ng/ml) and LH were each detectable in the media from 2 cultures. Although most of the hormone concentrations in the media decreased with length of time in culture, there were 2 exceptions. First in the media from 5 of the 12 cultures from both controls and tumours, Prl concentrations increased after 50 to 80 days culture. This increase usually lasted for several weeks before Prl levels again began to decline. The second unusual finding occurred in a tumour from a patient with acromegaly in the media of which hGH levels rose from 60 ng/ml to 800 ng/ml between days 125 and 174. These findings of prolonged hormone release in vitro give promise of future usefulness of tissue culture methods for study of polypeptide hormone releasing mechanisms and long-term production of human anterior pituitary hormones for use in research and possible therapy.", "contents": "Tissue culture studies on human pituitary tumours: long term release of anterior pituitary hormones into the culture medium. A study was undertaken to determine the length of time that human pituitary tumours are capable of releasing anterior pituitary polypeptide hormones in vitro under basal conditions and to study the spectrum of hormone release by functioning and \"non-functioning\" pituitary neoplasms. Fragments from the pituitary tumours of 10 patients in the following categories: 1 Cushing's disease, 2 with amenorrhoea-galactorrhoea, 3 with acromegaly, and 4 with \"non-functioning\" pituitary tumours and from 2 normal human anterior pituitary glands were placed in primary culture immediately after surgery. The in vitro release of human growth hormone (hGH), prolactin (Prl), thyrotrophin (TSH), adrenocorticotrophin (ACTH), luteinizing hormone (LH), and follicle stimulating hormone (FSH) was measured by specific radioimmunoassays at the end of each week in culture. Hormone release was surveyed from 6 weeks to 6 months depending upon the survival of the culture. Hormone release patterns were compared with clinical and pathological data. In the initial week of the study, all 6 anterior pituitary polypeptides were detected in the media from the 2 control pituitaries and from 4 of the tumours (1 amenorrhoea-galactorrhoea and 3 acromegaly) in concentrations up to 100 ng/ml of medium while 5 of the 6 hormones were readily detectable in the media from 2 additional tumour samples (Cushing's disease and 1 \"non-functioning\" pituitary tumour). The media of the remaining 4 tumours contained at least 3 of the 6 hormones (1 amenorrhoea-galactorrhoea and 3 \"non-functioning\" pituitary tumours). After 6 months in culture, the 6 hormones were readily detectable in at least 1 of the 5 surviving cultures and hGH (up to 800 ng/ml) and LH were each detectable in the media from 2 cultures. Although most of the hormone concentrations in the media decreased with length of time in culture, there were 2 exceptions. First in the media from 5 of the 12 cultures from both controls and tumours, Prl concentrations increased after 50 to 80 days culture. This increase usually lasted for several weeks before Prl levels again began to decline. The second unusual finding occurred in a tumour from a patient with acromegaly in the media of which hGH levels rose from 60 ng/ml to 800 ng/ml between days 125 and 174. These findings of prolonged hormone release in vitro give promise of future usefulness of tissue culture methods for study of polypeptide hormone releasing mechanisms and long-term production of human anterior pituitary hormones for use in research and possible therapy."}
{"id": "PMID:218414", "title": "17-Hydroxyprogesterone in the cosyntropin test: results in normal and hirsute women and in mild congenital adrenal hyperplasia.", "content": "The variations in plasma cortisol, testosterone and 17-hydroxyprogesterone (17-OHP) induced by an im injection of 0.25 mg cosyntrophin were studied in three groups of subjects: 16 healthy women, 16 hirsute women (HW) and 10 mild cases of congenital adrenal hyperplasia (CAH). The basal values of cortisol and testosterone were comparable between the three groups. In the patients with mild CAH, the mean 17-OHP concentration was increased: 483.9 ng/100 ml (113-1200 ng), but it should be noted that the individual values could overlap with the normal concentrations found in the controls and the HW during the luteal phase of the cycle. One hour after the injection of cosyntropin, a massive response of 17-OHP was observed in the mild cases of CAH, the mean basal concentration was multiplied by ten: 4843 ng/100 ml. The minimum concentration reached was 1740 ng/100 ml which is still 3-fold the highest level seen either in normal women (400 ng/ml) or in hirsute women (550 ng/100 ml). Determination of 17-OHP following a short-term ACTH stimulation, therefore provides evidence of partial 21-hydroxylase deficiency.", "contents": "17-Hydroxyprogesterone in the cosyntropin test: results in normal and hirsute women and in mild congenital adrenal hyperplasia. The variations in plasma cortisol, testosterone and 17-hydroxyprogesterone (17-OHP) induced by an im injection of 0.25 mg cosyntrophin were studied in three groups of subjects: 16 healthy women, 16 hirsute women (HW) and 10 mild cases of congenital adrenal hyperplasia (CAH). The basal values of cortisol and testosterone were comparable between the three groups. In the patients with mild CAH, the mean 17-OHP concentration was increased: 483.9 ng/100 ml (113-1200 ng), but it should be noted that the individual values could overlap with the normal concentrations found in the controls and the HW during the luteal phase of the cycle. One hour after the injection of cosyntropin, a massive response of 17-OHP was observed in the mild cases of CAH, the mean basal concentration was multiplied by ten: 4843 ng/100 ml. The minimum concentration reached was 1740 ng/100 ml which is still 3-fold the highest level seen either in normal women (400 ng/ml) or in hirsute women (550 ng/100 ml). Determination of 17-OHP following a short-term ACTH stimulation, therefore provides evidence of partial 21-hydroxylase deficiency."}
{"id": "PMID:218415", "title": "17 alpha-Hydroxylase deficiency. A combination of hydroxylation defect and reversible blockade in aldosterone biosynthesis.", "content": "We have studied the hormonal secretion and excretion patterns in a patient with the XX type of 17 alpha-hydroxylase deficiency. In the untreated state, the patient's urine contained only those steroids which do not require 17-hydroxylation in their biosynthesis. Aldosterone was not produced in the patient and the metabolic product of its immediate precursor, 18-hydroxy-11-dehydro-tetrahydrocorticosterone, was excreted in markedly elevated amounts. This apparent complete block in 18 oxidation was reversible upon long-term ACTH suppression within 27 days. Direct in vitro incubation of the patient's adrenal gland removed at operation demonstrated, 1) the complete lack of 17 alpha-hydroxylase activity, 2) the functional block in the ability to oxidize the hydroxyl group at the 18 methyl side chain. The addition of physiological concentrations of angiotensin to the incubation medium further showed, 3) angiotensin mildly stimulated the entire aldosterone biosynthetic pathway, 4) angiotensin directly stimulated the conversion of 18-hydroxycorticosterone to aldosterone. We propose that in this patient, 17-hydroxylase deficiency produced a decreased plasma concentration of cortisol, followed by stimulation of deoxycorticosterone production by ACTH. The resultant increase in extracellular fluid volume suppressed plasma renin activity. This resulted in a low plasma concentration of angiotensin II which directly suppressed oxidation of 18-hydroxycorticosterone to aldosterone. This defect has been called corticosterone methyl oxidase defect type 2.", "contents": "17 alpha-Hydroxylase deficiency. A combination of hydroxylation defect and reversible blockade in aldosterone biosynthesis. We have studied the hormonal secretion and excretion patterns in a patient with the XX type of 17 alpha-hydroxylase deficiency. In the untreated state, the patient's urine contained only those steroids which do not require 17-hydroxylation in their biosynthesis. Aldosterone was not produced in the patient and the metabolic product of its immediate precursor, 18-hydroxy-11-dehydro-tetrahydrocorticosterone, was excreted in markedly elevated amounts. This apparent complete block in 18 oxidation was reversible upon long-term ACTH suppression within 27 days. Direct in vitro incubation of the patient's adrenal gland removed at operation demonstrated, 1) the complete lack of 17 alpha-hydroxylase activity, 2) the functional block in the ability to oxidize the hydroxyl group at the 18 methyl side chain. The addition of physiological concentrations of angiotensin to the incubation medium further showed, 3) angiotensin mildly stimulated the entire aldosterone biosynthetic pathway, 4) angiotensin directly stimulated the conversion of 18-hydroxycorticosterone to aldosterone. We propose that in this patient, 17-hydroxylase deficiency produced a decreased plasma concentration of cortisol, followed by stimulation of deoxycorticosterone production by ACTH. The resultant increase in extracellular fluid volume suppressed plasma renin activity. This resulted in a low plasma concentration of angiotensin II which directly suppressed oxidation of 18-hydroxycorticosterone to aldosterone. This defect has been called corticosterone methyl oxidase defect type 2."}
{"id": "PMID:218416", "title": "Response of plasma non-conjugated oestradiol to manipulated adrenal function by ACTH and dexamethasone.", "content": "The present study is concerned with the regulation of free plasma oestradiol in relation to maternal adrenal function during late human pregnancy. Blood was collected in 9 patients at short time intervals of 30 min from 17 h to 3 h. In order to exclude endogenous ACTH-secretion 5 patients received 12 mg dexamethasone over 48 h. Between 20 h and 2 h 0.25 mg ACTH1-24 (Synacthen) was infused into the subjects. Non-conjugated oestradiol was determined by radioimmunoassay and total plasma cortisol by protein binding method. During the application of ACTH free oestradiol increased from 21.3 +/- 5.7 to 25.5 +/- 7.1 ng/ml (P less than 0.025) in the patients without dexamethasone. The increase was moderately correlated to rising cortisol (r = 0.58, P less than 0.001). Plasma oestradiol reached its maximum level after 90 min, followed by a tendency to decline despite persisting stimulation of maternal adrenals. The patients receiving dexamethasone exhibited during ACTH-infusion a rise of oestradiol from 3.8 +/- 1.9 to 7.8 +/- 3.1 ng/ml (P less than 0.001). Increasing oestradiol was strongly correlated to plasma cortisol (r = 0.67, P less than 0.001). The phenomenon of earlier declining oestradiol levels did not occur. These results suggest that maternal adrenals predominantly regulate the formation of free oestradiol. Plasma cortisol indicating maternal precursor production balances the increase of oestradiol by suppressing foetal precursor supply.", "contents": "Response of plasma non-conjugated oestradiol to manipulated adrenal function by ACTH and dexamethasone. The present study is concerned with the regulation of free plasma oestradiol in relation to maternal adrenal function during late human pregnancy. Blood was collected in 9 patients at short time intervals of 30 min from 17 h to 3 h. In order to exclude endogenous ACTH-secretion 5 patients received 12 mg dexamethasone over 48 h. Between 20 h and 2 h 0.25 mg ACTH1-24 (Synacthen) was infused into the subjects. Non-conjugated oestradiol was determined by radioimmunoassay and total plasma cortisol by protein binding method. During the application of ACTH free oestradiol increased from 21.3 +/- 5.7 to 25.5 +/- 7.1 ng/ml (P less than 0.025) in the patients without dexamethasone. The increase was moderately correlated to rising cortisol (r = 0.58, P less than 0.001). Plasma oestradiol reached its maximum level after 90 min, followed by a tendency to decline despite persisting stimulation of maternal adrenals. The patients receiving dexamethasone exhibited during ACTH-infusion a rise of oestradiol from 3.8 +/- 1.9 to 7.8 +/- 3.1 ng/ml (P less than 0.001). Increasing oestradiol was strongly correlated to plasma cortisol (r = 0.67, P less than 0.001). The phenomenon of earlier declining oestradiol levels did not occur. These results suggest that maternal adrenals predominantly regulate the formation of free oestradiol. Plasma cortisol indicating maternal precursor production balances the increase of oestradiol by suppressing foetal precursor supply."}
{"id": "PMID:218419", "title": "Effect of propranolol on the plasma cyclic AMP and cyclic GMP levels to massive doses of glucagon in euthyroid and hyperthyroid subjects.", "content": "The plasma c-AMP level increases significantly in response to pharmacologica doses (1 mg i. v.) of glucaton. Beta blocking agents somewhat inhibit this increase in both euthyroid and hyperthyroid subjects. Catecholamine release elicited by glucagon thus plays some part in the response. In euthyroid subjects 2 microgram/kg glucagon still produces a significant increase in the plasma c-AMP concentration and propranolol fails to counteract this response. The c-AMP response elicited by identical doses of glucagon is more marked in hyperthyroid than in euthyroid subjects and can be somewhat reduced by propranolol. This indicates that in hyperthyroid patients even low doses of glucagon stimulate the release of catecholamines or enhance the responsiveness of beta receptors. The plasma c-GMP level increases in response to glucagon loading but in a lesser degree than does the c-AMP concentration. The response of c-GMP to glucagon is more protracted than the response of c-AMP and propranolol fails to counteract it.", "contents": "Effect of propranolol on the plasma cyclic AMP and cyclic GMP levels to massive doses of glucagon in euthyroid and hyperthyroid subjects. The plasma c-AMP level increases significantly in response to pharmacologica doses (1 mg i. v.) of glucaton. Beta blocking agents somewhat inhibit this increase in both euthyroid and hyperthyroid subjects. Catecholamine release elicited by glucagon thus plays some part in the response. In euthyroid subjects 2 microgram/kg glucagon still produces a significant increase in the plasma c-AMP concentration and propranolol fails to counteract this response. The c-AMP response elicited by identical doses of glucagon is more marked in hyperthyroid than in euthyroid subjects and can be somewhat reduced by propranolol. This indicates that in hyperthyroid patients even low doses of glucagon stimulate the release of catecholamines or enhance the responsiveness of beta receptors. The plasma c-GMP level increases in response to glucagon loading but in a lesser degree than does the c-AMP concentration. The response of c-GMP to glucagon is more protracted than the response of c-AMP and propranolol fails to counteract it."}
{"id": "PMID:218420", "title": "Comparison of pituitary-adrenocortical response to hypoglycaemia and surgery.", "content": "The hypothalamic-pituitary-adrenocortical (HPA) responses to the hypoglycaemic stimulus and to operation (laparotomy) are compared. The studies were carried out in eight patients who were subjected to insulin-induced hypoglycaemia on the day before elective abdominal surgery. Plasma corticotrophin (ACTH) and plasma cortisol concentration increases were virtually indentical during the two procedures, which suggests that hypoglycaemia and surgical trauma are comparable stress factors and that the hypoglycaemia test is reliable in predicting the HPA responses to major surgical trauma.", "contents": "Comparison of pituitary-adrenocortical response to hypoglycaemia and surgery. The hypothalamic-pituitary-adrenocortical (HPA) responses to the hypoglycaemic stimulus and to operation (laparotomy) are compared. The studies were carried out in eight patients who were subjected to insulin-induced hypoglycaemia on the day before elective abdominal surgery. Plasma corticotrophin (ACTH) and plasma cortisol concentration increases were virtually indentical during the two procedures, which suggests that hypoglycaemia and surgical trauma are comparable stress factors and that the hypoglycaemia test is reliable in predicting the HPA responses to major surgical trauma."}
{"id": "PMID:218421", "title": "Origin and function of 'rod-like structures' in mitochondria.", "content": "Both organ culture (choriallantoic membrane) of striped muscle from mouse diaphragm and freeze-drying of myocardial cells presented very characteristic structures in mitochondria. The organ culture evidence 'rod-like structures' in the intracristal spaces of the cristae mitochondriales. It is believed that these structures are the central apparatus responsible for mitochondrial division. On the other hand, the freeze-dried mitochondria presented neither intracristal spaces nor a space in the outer mitochondrial membrane. Because these spaces appeared only after fixation and dehydration, it is discussed if they are really artifacts. The mitochondrial cristae appearing as united structures after the freeze-drying process have been compared to the rod-like structures appearing intracristally after organ culture and conventional preparation techniques.", "contents": "Origin and function of 'rod-like structures' in mitochondria. Both organ culture (choriallantoic membrane) of striped muscle from mouse diaphragm and freeze-drying of myocardial cells presented very characteristic structures in mitochondria. The organ culture evidence 'rod-like structures' in the intracristal spaces of the cristae mitochondriales. It is believed that these structures are the central apparatus responsible for mitochondrial division. On the other hand, the freeze-dried mitochondria presented neither intracristal spaces nor a space in the outer mitochondrial membrane. Because these spaces appeared only after fixation and dehydration, it is discussed if they are really artifacts. The mitochondrial cristae appearing as united structures after the freeze-drying process have been compared to the rod-like structures appearing intracristally after organ culture and conventional preparation techniques."}
{"id": "PMID:218422", "title": "Ultrastructure of the nerve cells and fibres in the urinary bladder wall of the cat.", "content": "The nerve elements in the urinary bladder of the cat were studied by electron microscopy. According to their ultrastructure, nerve cell somata can be classified into three types: the large cells with a cytoplasm rich in organelles, several processes and numerous synaptic contacts on their surface; the cytoplasm contained 80- 120-nm granulated vesicles. The second type is poor in cytoplasmic organelles and has very few processes and virtually no synaptic contacts on the soma. The third type contains numerous large 160- to 220-nm 'neurosecretory' vesicles in the cytoplasm. According to the morphology of the vesicle population, four types of nerve processes could be distinguished: Type a, with a dominant population of small (40-60 nm) agranular vesicles. These are thought to be sacral parasympathetic fibres. Type b, with small (40-60 nm) granular vesicles, which may be the noradrenergic sympathetic fibres. Type c, with 80- to 120-nm granulated vesicles, probably of local origin. Typed d, with large 160- to 220-nm 'neurosecretory' vesicles also of local origin. Different types of nerve fibres are converging on the local nerve cells. This suggests that the local circuits can play an important role in coordinating the function of the bladder. Therefore, ganglia may be considered as an elementary functional unit.", "contents": "Ultrastructure of the nerve cells and fibres in the urinary bladder wall of the cat. The nerve elements in the urinary bladder of the cat were studied by electron microscopy. According to their ultrastructure, nerve cell somata can be classified into three types: the large cells with a cytoplasm rich in organelles, several processes and numerous synaptic contacts on their surface; the cytoplasm contained 80- 120-nm granulated vesicles. The second type is poor in cytoplasmic organelles and has very few processes and virtually no synaptic contacts on the soma. The third type contains numerous large 160- to 220-nm 'neurosecretory' vesicles in the cytoplasm. According to the morphology of the vesicle population, four types of nerve processes could be distinguished: Type a, with a dominant population of small (40-60 nm) agranular vesicles. These are thought to be sacral parasympathetic fibres. Type b, with small (40-60 nm) granular vesicles, which may be the noradrenergic sympathetic fibres. Type c, with 80- to 120-nm granulated vesicles, probably of local origin. Typed d, with large 160- to 220-nm 'neurosecretory' vesicles also of local origin. Different types of nerve fibres are converging on the local nerve cells. This suggests that the local circuits can play an important role in coordinating the function of the bladder. Therefore, ganglia may be considered as an elementary functional unit."}
{"id": "PMID:218425", "title": "A simple large-scale method for separating closed circular form DNA by gel electrophoresis.", "content": "The covalently closed form of circular duplex SV40 DNA was separated from the open and linear form of SV40 DNA by agarose gel electrophoresis in a large-scale gel system. The closed circular DNA was recovered from agarose gels by re-electrophoresing the gel slices. The recovery of DNA was about 70%. Electron microscopic analysis showed that the recovered DNA did not have doube- or single-stranded breaks. The recovered DNA can be used without further purification for electron microscopy, as a substrate for experiments using restriction endonuclease and as a template for in vitro RNA synthesis.", "contents": "A simple large-scale method for separating closed circular form DNA by gel electrophoresis. The covalently closed form of circular duplex SV40 DNA was separated from the open and linear form of SV40 DNA by agarose gel electrophoresis in a large-scale gel system. The closed circular DNA was recovered from agarose gels by re-electrophoresing the gel slices. The recovery of DNA was about 70%. Electron microscopic analysis showed that the recovered DNA did not have doube- or single-stranded breaks. The recovered DNA can be used without further purification for electron microscopy, as a substrate for experiments using restriction endonuclease and as a template for in vitro RNA synthesis."}
{"id": "PMID:218426", "title": "Metabolic studies and glucagon gel filtration pattern before and after surgery in a case of glucagonoma syndrome.", "content": "A case of glucagonoma syndrome with necrolytic migratory erythema, glossitis, anemia, hyperglucagonemia and a malignant, pancreatic A-cell tumour in a 68-year-old male is described. Gel filtration of the highly elevated circulating glucagon immunoreactivity (2200 pg/ml) demonstrated 60% pancreatic glucagon and 30% \"proglucagon\". Metabolic studies before operation demonstrated suppression of the total plasma glucagon concentration on oral glucose tolerance test, unchanged total plasma glucagon concentration during intravenous glucose tolerance test and insulin-induced hypoglycemia. Administration of arginine was followed by a rise in both the pancreatic glucagon and the \"proglucagon\", whereas alanine increased only the pancreatic glucagon. The plasma somatostatin level was immeasurable preoperatively. Somatostatin infusion completely suppressed the release of the pancreatic glucagon but did not significantly affect the \"proglucagon\". After removal of the tumour the skin lesions disappeared and the total plasma glucagon values fell to normal levels (120 pg/ml). Also, other abnormal laboratory findings returned to normal, including the preoperatively observed renal glucosuria.", "contents": "Metabolic studies and glucagon gel filtration pattern before and after surgery in a case of glucagonoma syndrome. A case of glucagonoma syndrome with necrolytic migratory erythema, glossitis, anemia, hyperglucagonemia and a malignant, pancreatic A-cell tumour in a 68-year-old male is described. Gel filtration of the highly elevated circulating glucagon immunoreactivity (2200 pg/ml) demonstrated 60% pancreatic glucagon and 30% \"proglucagon\". Metabolic studies before operation demonstrated suppression of the total plasma glucagon concentration on oral glucose tolerance test, unchanged total plasma glucagon concentration during intravenous glucose tolerance test and insulin-induced hypoglycemia. Administration of arginine was followed by a rise in both the pancreatic glucagon and the \"proglucagon\", whereas alanine increased only the pancreatic glucagon. The plasma somatostatin level was immeasurable preoperatively. Somatostatin infusion completely suppressed the release of the pancreatic glucagon but did not significantly affect the \"proglucagon\". After removal of the tumour the skin lesions disappeared and the total plasma glucagon values fell to normal levels (120 pg/ml). Also, other abnormal laboratory findings returned to normal, including the preoperatively observed renal glucosuria."}
{"id": "PMID:218427", "title": "Differences in metabolic responses to beta-adrenergic stimulation after propranolol or metoprolol administration.", "content": "Isoprenaline, or the beta 2-agonist terbutaline, was infused in healthy male volunteers and the plasma levels of insulin, glucose and free fatty acids (FFA) were determined. Saline, propranolol, or the selective beta 1-receptor antagonist, metoprolol, was administered i.v. prior to the infusion of the beta-stimulants. The two beta-receptor blockers inhibited isoprenaline-induced increase in chronotropy to about the same extent, while the effects on systolic and diastolic blood pressure were in accordance with a selective beta1-blocking effect of metoprolol and a non-selective beta-blocking action of propranolol. Quantitative differences were found between metoprolol and propranolol on the metabolic parameters. The effects can best be described in terms of beta 1- or beta 2-receptors, where effects on plasma FFA and glycerol levels seem to be mainly beta1-mediated. An apparent beta 2-mediated effect was found for insulin release and hepatic glucose output.", "contents": "Differences in metabolic responses to beta-adrenergic stimulation after propranolol or metoprolol administration. Isoprenaline, or the beta 2-agonist terbutaline, was infused in healthy male volunteers and the plasma levels of insulin, glucose and free fatty acids (FFA) were determined. Saline, propranolol, or the selective beta 1-receptor antagonist, metoprolol, was administered i.v. prior to the infusion of the beta-stimulants. The two beta-receptor blockers inhibited isoprenaline-induced increase in chronotropy to about the same extent, while the effects on systolic and diastolic blood pressure were in accordance with a selective beta1-blocking effect of metoprolol and a non-selective beta-blocking action of propranolol. Quantitative differences were found between metoprolol and propranolol on the metabolic parameters. The effects can best be described in terms of beta 1- or beta 2-receptors, where effects on plasma FFA and glycerol levels seem to be mainly beta1-mediated. An apparent beta 2-mediated effect was found for insulin release and hepatic glucose output."}
{"id": "PMID:218428", "title": "Peripheral neuropathy in monoclonal gammapathy with cryoglobulinemia and arteritis.", "content": "We report a patient with IgM gammapathy, cryoglobulinemia, Raynaud's phenomena, purpura hyperglobulinemica of the legs and polyneuropathy. Endoneural vasculitis with infiltrations of eosinophilic and neutrophilic granulocytes and an extensive loss or Wallerian degeneration of myelinated nerve fibers were seen on histopathologic examination of a sural nerve biopsy specimen. The microscopic picture differed somewhat from that observed previously in cryoglobulinemic vasculitis. Although vasculitis is most often believed to represent an immunologically mediated lesion, we propose an alternate explanation, namely, that the disease manifestations in the present case were secondary to cold-induced effects of the cryoglobulin on the microcirculation.", "contents": "Peripheral neuropathy in monoclonal gammapathy with cryoglobulinemia and arteritis. We report a patient with IgM gammapathy, cryoglobulinemia, Raynaud's phenomena, purpura hyperglobulinemica of the legs and polyneuropathy. Endoneural vasculitis with infiltrations of eosinophilic and neutrophilic granulocytes and an extensive loss or Wallerian degeneration of myelinated nerve fibers were seen on histopathologic examination of a sural nerve biopsy specimen. The microscopic picture differed somewhat from that observed previously in cryoglobulinemic vasculitis. Although vasculitis is most often believed to represent an immunologically mediated lesion, we propose an alternate explanation, namely, that the disease manifestations in the present case were secondary to cold-induced effects of the cryoglobulin on the microcirculation."}
{"id": "PMID:218430", "title": "Hormonal control of glycogen metabolism.", "content": "In summary, we have presented evidence which relates to the action pathway of hormonal control of glycogen metabolism. In the case of insulin, there are changes demonstrable in the cyclic AMP-dependent protein kinase and also in the phosphoprotein phosphatase, under conditions where no direct relationship to either cyclic AMP or cyclic GMP levels are measurable. Therefore, a new unknown intermediate or second messenger system is again proposed. An insulin-generated labile compound(s) which inhibits the protein kinase has been discovered. This may function as an intermediate. Finally, the fact that the glycogen synthase system clearly differs from phosphorylase in its regulation by covalent phosphorylation is discussed. Synthase is now accepted as a multiply phosphorylated subunit, in contrast to phosphorylase which is singly phosphorylated. The inherent theoretical advantages of multiple phosphorylation over single phosphorylation are considered. The advantages of a multistate over a two-state model of enzyme interconversion are mentioned. The importance of the multiple phosphorylations interacting in a nonlinear manner with the control by cellular metabolites is in the explanation of how a small change in covalent phosphorylation signalled by a hormone can be translated in the cell milieu into a much larger change in rate.", "contents": "Hormonal control of glycogen metabolism. In summary, we have presented evidence which relates to the action pathway of hormonal control of glycogen metabolism. In the case of insulin, there are changes demonstrable in the cyclic AMP-dependent protein kinase and also in the phosphoprotein phosphatase, under conditions where no direct relationship to either cyclic AMP or cyclic GMP levels are measurable. Therefore, a new unknown intermediate or second messenger system is again proposed. An insulin-generated labile compound(s) which inhibits the protein kinase has been discovered. This may function as an intermediate. Finally, the fact that the glycogen synthase system clearly differs from phosphorylase in its regulation by covalent phosphorylation is discussed. Synthase is now accepted as a multiply phosphorylated subunit, in contrast to phosphorylase which is singly phosphorylated. The inherent theoretical advantages of multiple phosphorylation over single phosphorylation are considered. The advantages of a multistate over a two-state model of enzyme interconversion are mentioned. The importance of the multiple phosphorylations interacting in a nonlinear manner with the control by cellular metabolites is in the explanation of how a small change in covalent phosphorylation signalled by a hormone can be translated in the cell milieu into a much larger change in rate."}
{"id": "PMID:218432", "title": "Regulation of insulin receptors in normal and abnormal physiology in humans.", "content": "Insulin receptors in human tissue undergo marked changes in both their concentration and their affinity for insulin. In general, alterations in receptor affinity are associated with rapidly changing metabolic environments and can occur within hours, whereas alterations in receptor concentration appear to require longer time periods for their induction. The association of a given type of receptor alteration (i.e., change in affinity or concentration) with a given clinical state indicates the presence of distinct modulators of the insulin-receptor interaction. We have presented evidence for 2 specific modulators, i.e., insulin itself and anti-insulin-receptor antibodies. In several clinical states, especially those associated with changes in receptor affinity, receptor alterations are unrelated to either ambient insulin levels or anti-receptor antibodies, suggesting the presence of several as yet unknown mediators of the insulin receptor. The direct metabolic consequences of these receptor events are not well established. In several states, the receptor alteration correlated quite well with the clinical sensitivity of the whole organism to insulin, indirectly implicating the receptor as the major control point for insulin sensitivity. In contrast, specific examples were cited in which receptor events are not consonant with observed biologic responses to insulin, thereby suggesting a predominance of postreceptor processes. Finally, it should be emphasized that the study of hormone receptors and their relationship to disease states is in the formative stage. With new and improved methodology we hope we will be able to investigate the entire pathway of insulin action at its target tissues, from the initial receptor binding to the final biologic effect.", "contents": "Regulation of insulin receptors in normal and abnormal physiology in humans. Insulin receptors in human tissue undergo marked changes in both their concentration and their affinity for insulin. In general, alterations in receptor affinity are associated with rapidly changing metabolic environments and can occur within hours, whereas alterations in receptor concentration appear to require longer time periods for their induction. The association of a given type of receptor alteration (i.e., change in affinity or concentration) with a given clinical state indicates the presence of distinct modulators of the insulin-receptor interaction. We have presented evidence for 2 specific modulators, i.e., insulin itself and anti-insulin-receptor antibodies. In several clinical states, especially those associated with changes in receptor affinity, receptor alterations are unrelated to either ambient insulin levels or anti-receptor antibodies, suggesting the presence of several as yet unknown mediators of the insulin receptor. The direct metabolic consequences of these receptor events are not well established. In several states, the receptor alteration correlated quite well with the clinical sensitivity of the whole organism to insulin, indirectly implicating the receptor as the major control point for insulin sensitivity. In contrast, specific examples were cited in which receptor events are not consonant with observed biologic responses to insulin, thereby suggesting a predominance of postreceptor processes. Finally, it should be emphasized that the study of hormone receptors and their relationship to disease states is in the formative stage. With new and improved methodology we hope we will be able to investigate the entire pathway of insulin action at its target tissues, from the initial receptor binding to the final biologic effect."}
{"id": "PMID:218435", "title": "Contrast enhanced CT scan and radionuclide brain scan in supratentorial gliomas.", "content": "The preoperative contrast enhanced CT and radionuclide brain scans of 60 patients with surgically verified supratentorial astrocytomas were evaluated and compared. Results indicated that the mechanisms of contrast enhancement and radionuclide uptake are identical in the detection of supratentorial gliomas. These diagnostic methods apparently mirror the integrity of the blood-brain barrier and therefore can be useful in assessing the degree of malignancy of supratentorial gliomas. However, lesions with an intact blood-brain barrier will be missed with radionuclide imaging. These parenchymal abnormalities and/or the associated mass effect will be detected with contrast enhanced computed tomography. These findings firmly establish contrast enhanced computed tomography. These findings firmly establish contrast enhanced CT as the primary investigate tool in the suspected brain tumor.", "contents": "Contrast enhanced CT scan and radionuclide brain scan in supratentorial gliomas. The preoperative contrast enhanced CT and radionuclide brain scans of 60 patients with surgically verified supratentorial astrocytomas were evaluated and compared. Results indicated that the mechanisms of contrast enhancement and radionuclide uptake are identical in the detection of supratentorial gliomas. These diagnostic methods apparently mirror the integrity of the blood-brain barrier and therefore can be useful in assessing the degree of malignancy of supratentorial gliomas. However, lesions with an intact blood-brain barrier will be missed with radionuclide imaging. These parenchymal abnormalities and/or the associated mass effect will be detected with contrast enhanced computed tomography. These findings firmly establish contrast enhanced computed tomography. These findings firmly establish contrast enhanced CT as the primary investigate tool in the suspected brain tumor."}
{"id": "PMID:218439", "title": "Viral type A and type B hepatitis: morphology, biology, immunology and epidemiology--a review.", "content": "Viral hepatitis is one of the most serious infectious diseases in the United States and is of great concern to the public health agencies, hospitals and research laboratories. Progress in our knowledge of this disease has been based on cooperation between specialists in many diverse scientific disciplines employing sophisticated scientific instruments and technics. Close cooperation between clinical pathologists and clinicians is of great importance in diagnosis. Biologic, immunologic, epidemiologic and morphologic studies have resulted in the demonstration that the disease is the result of infection with at least two different viruses, described as type A and type B hepatitis viruses. The first induces type A hepatitis (infectious or epidemic, or MS-2 strain) of longer incubation period, is transmitted parenterally and apparently by inhalation or ingestion of virus-containing material, by venereal means as well as by other means. Extremely sensitive methods are now available for the detection of hepatitis type B infection, based on the results of biochemical, biophysical and immunoelectronmicroscopic studies that resulted in our knowledge of structure and composition of type B virus, and our knowledge of host immune responses to the various components of this virus. Thus it is now known that two antigen-antibody systems are associated with viral hepatitis type B: hepatitis B surface antigen (HBsAg) and antibody (HBsAb) and hepatitis B core antigen (HBcAg) and antibody to it (HBcAb). The test for antibody to HBcAg appears to be a sensitive indicator of viral replication when only subdetectable amounts of HBsAg are circulated. Since the recent discovery and characterization of type A hepatitis virus, great progress has been made in our understanding of the relationship between type A and type B hepatitis viruses. There is no cross immunity between the two viruses, and as is now suspected, there may be at least another virus, described as type C virus, which may play an etiologic role in viral hepatitis. There is no doubt now that type A and type B hepatitis viruses can be transmitted to monkeys; type A to marmosets and chimpanzees, type B to chimpanzees and rhesus monkeys. The two viruses are serologically and immunologically distinct. This knowledge and the results of biologic experiments have laid a solid foundation of meaningful diagnostic procedures for the two types of viral hepatitis. Advances in biophysical and biochemical procedures of treatment of sera of hepatitis B patients have resulted in availability of viral material, noninfectious but immunogenic, for vaccination of chimpanzees. Protective efficacy trials of the vaccine in chimpanzees have demonstrated the vaccine to be fully protective against high doses of infectious hepatitis B virus...", "contents": "Viral type A and type B hepatitis: morphology, biology, immunology and epidemiology--a review. Viral hepatitis is one of the most serious infectious diseases in the United States and is of great concern to the public health agencies, hospitals and research laboratories. Progress in our knowledge of this disease has been based on cooperation between specialists in many diverse scientific disciplines employing sophisticated scientific instruments and technics. Close cooperation between clinical pathologists and clinicians is of great importance in diagnosis. Biologic, immunologic, epidemiologic and morphologic studies have resulted in the demonstration that the disease is the result of infection with at least two different viruses, described as type A and type B hepatitis viruses. The first induces type A hepatitis (infectious or epidemic, or MS-2 strain) of longer incubation period, is transmitted parenterally and apparently by inhalation or ingestion of virus-containing material, by venereal means as well as by other means. Extremely sensitive methods are now available for the detection of hepatitis type B infection, based on the results of biochemical, biophysical and immunoelectronmicroscopic studies that resulted in our knowledge of structure and composition of type B virus, and our knowledge of host immune responses to the various components of this virus. Thus it is now known that two antigen-antibody systems are associated with viral hepatitis type B: hepatitis B surface antigen (HBsAg) and antibody (HBsAb) and hepatitis B core antigen (HBcAg) and antibody to it (HBcAb). The test for antibody to HBcAg appears to be a sensitive indicator of viral replication when only subdetectable amounts of HBsAg are circulated. Since the recent discovery and characterization of type A hepatitis virus, great progress has been made in our understanding of the relationship between type A and type B hepatitis viruses. There is no cross immunity between the two viruses, and as is now suspected, there may be at least another virus, described as type C virus, which may play an etiologic role in viral hepatitis. There is no doubt now that type A and type B hepatitis viruses can be transmitted to monkeys; type A to marmosets and chimpanzees, type B to chimpanzees and rhesus monkeys. The two viruses are serologically and immunologically distinct. This knowledge and the results of biologic experiments have laid a solid foundation of meaningful diagnostic procedures for the two types of viral hepatitis. Advances in biophysical and biochemical procedures of treatment of sera of hepatitis B patients have resulted in availability of viral material, noninfectious but immunogenic, for vaccination of chimpanzees. Protective efficacy trials of the vaccine in chimpanzees have demonstrated the vaccine to be fully protective against high doses of infectious hepatitis B virus..."}
{"id": "PMID:218440", "title": "Detection of viral hepatitis type A.", "content": "Several technics are currently being used to detect hepatitis type A antigen or its antibody. These include immunoelectronmicroscopy, immune adherence, and complement fixation. This paper describes another promising technic, a microtiter solid-phase immunoradiometric assay, in which hepatitis A antigen and antibody are detected. Such a method can be utilized for biochemical and biophysical analysis of purified particles, for the seroepidemiology of type A hepatitis, and as a means for monitoring hepatitis A antigen in cell cultures.", "contents": "Detection of viral hepatitis type A. Several technics are currently being used to detect hepatitis type A antigen or its antibody. These include immunoelectronmicroscopy, immune adherence, and complement fixation. This paper describes another promising technic, a microtiter solid-phase immunoradiometric assay, in which hepatitis A antigen and antibody are detected. Such a method can be utilized for biochemical and biophysical analysis of purified particles, for the seroepidemiology of type A hepatitis, and as a means for monitoring hepatitis A antigen in cell cultures."}
{"id": "PMID:218441", "title": "Genetic factors and autoimmunity in viral hepatitis.", "content": "Whether a patient develops the HBsAg carrier state may depend on his genome. HBsAg subtypes may reflect the viral genome and may be of prognostic significance. Different subtypes predominate in different populations throughout the world. Altered immune response, as in patients with Down's syndrome, may increase the HBsAg carrier rate. Autoantibodies have been used to differentiate various types of hepatitis. There is an increased incidence of histocompatibility antigen HL-A1 and HL-A8 in patients who have chronic aggressive hepatitis. In primary hepatic carcinoma, the HBsAg carrier rate is increased. Because of the suggestion that neonatal hepatitis, biliary atresia and choledochal cyst may all result from infantile obstructive cholangiopathy, with the precise outcome depending on whether other conditions such as alpha 1-antitrypsin deficiency are also present, we have determined HBsAg in 166 children with a variety of diseases, among them Reye's syndrome, alpha 1-antitrypsin deficiency, and renal disorders. The HBsAg carrier rate in the sera of these patients was normal.", "contents": "Genetic factors and autoimmunity in viral hepatitis. Whether a patient develops the HBsAg carrier state may depend on his genome. HBsAg subtypes may reflect the viral genome and may be of prognostic significance. Different subtypes predominate in different populations throughout the world. Altered immune response, as in patients with Down's syndrome, may increase the HBsAg carrier rate. Autoantibodies have been used to differentiate various types of hepatitis. There is an increased incidence of histocompatibility antigen HL-A1 and HL-A8 in patients who have chronic aggressive hepatitis. In primary hepatic carcinoma, the HBsAg carrier rate is increased. Because of the suggestion that neonatal hepatitis, biliary atresia and choledochal cyst may all result from infantile obstructive cholangiopathy, with the precise outcome depending on whether other conditions such as alpha 1-antitrypsin deficiency are also present, we have determined HBsAg in 166 children with a variety of diseases, among them Reye's syndrome, alpha 1-antitrypsin deficiency, and renal disorders. The HBsAg carrier rate in the sera of these patients was normal."}
{"id": "PMID:218442", "title": "Isolation and characterization of hepatitis A virus.", "content": "This paper presents current isolation technics of hepatitis A virus (HAV) from human and chimpanzee stool, liver, and bile specimens, as well as comparative characterizations of HAV buoyant density properties of human and chimpanzee stool-derived particles. In addition, methods designed for the extraction and purification of HAV from large samples of stool and liver tissues, including agar gel filtration, are discussed in detail.", "contents": "Isolation and characterization of hepatitis A virus. This paper presents current isolation technics of hepatitis A virus (HAV) from human and chimpanzee stool, liver, and bile specimens, as well as comparative characterizations of HAV buoyant density properties of human and chimpanzee stool-derived particles. In addition, methods designed for the extraction and purification of HAV from large samples of stool and liver tissues, including agar gel filtration, are discussed in detail."}
{"id": "PMID:218443", "title": "Blast cell leukemia with IgM monoclonal gammopathy and intracytoplasmic vacuoles and Auer-body-like inclusions.", "content": "A patient with acute leukemia and an IgM, kappa (IgMkappa) monoclonal gammopathy, Bence-Jones proteinuria, and blasts containing intracytoplasmic vacuoles with peroxidase-positive inclusions is discussed. Special stains, immunofluorescence, and electron microscopy suggested that the vacuoles were autophagosomes containing Auer-body-like inclusions, and that the blast cells did not synthesize the paraprotein. Chemotherapy with cyclophosphamide, vincristine, and prednisone resulted in transient improvement of the leukemia, but the level of the paraprotein was unchanged. Other case reports involving monoclonal gammopathy in association with acute leukemia are reviewed and contrasted with this case.", "contents": "Blast cell leukemia with IgM monoclonal gammopathy and intracytoplasmic vacuoles and Auer-body-like inclusions. A patient with acute leukemia and an IgM, kappa (IgMkappa) monoclonal gammopathy, Bence-Jones proteinuria, and blasts containing intracytoplasmic vacuoles with peroxidase-positive inclusions is discussed. Special stains, immunofluorescence, and electron microscopy suggested that the vacuoles were autophagosomes containing Auer-body-like inclusions, and that the blast cells did not synthesize the paraprotein. Chemotherapy with cyclophosphamide, vincristine, and prednisone resulted in transient improvement of the leukemia, but the level of the paraprotein was unchanged. Other case reports involving monoclonal gammopathy in association with acute leukemia are reviewed and contrasted with this case."}
{"id": "PMID:218444", "title": "Radiometric detection of Haemophilus in simulated blood cultures.", "content": "The radiometric detection of various Haemophilus species was studied in simulated blood cultures and in blood culture media without added blood, but supplemented with nicotinamide-adenine dinucleotide (NAD) or hemin, or both. Haemophilus aphrophilus was the only species studied that was radiometrically detectable without added blood or NAD. All other species studied (Haemophilus influenzae, Haemophilus parainfluenzae, Haemophilus haemolyticus, and Haemophilus parahaemolyticus) required either added NAD, whole blood, or washed blood cells for growth and radiometric detection. The results of this study and extensive experience with clinical specimens show that the radiometric system is an effective means of rapidly detecting Haemophilus in blood cultures, but it is essential that it be used in conjunction with a subculture three to five days after inoculation.", "contents": "Radiometric detection of Haemophilus in simulated blood cultures. The radiometric detection of various Haemophilus species was studied in simulated blood cultures and in blood culture media without added blood, but supplemented with nicotinamide-adenine dinucleotide (NAD) or hemin, or both. Haemophilus aphrophilus was the only species studied that was radiometrically detectable without added blood or NAD. All other species studied (Haemophilus influenzae, Haemophilus parainfluenzae, Haemophilus haemolyticus, and Haemophilus parahaemolyticus) required either added NAD, whole blood, or washed blood cells for growth and radiometric detection. The results of this study and extensive experience with clinical specimens show that the radiometric system is an effective means of rapidly detecting Haemophilus in blood cultures, but it is essential that it be used in conjunction with a subculture three to five days after inoculation."}
{"id": "PMID:218445", "title": "Cytoplasmic hepatitis B surface antigen and the ground-glass appearance in hepatocellular carcinoma.", "content": "Hepatitis B surface antigen (HBsAg) was identified with aldehyde fuchsin and immunoperoxidase stain and by immunofluorescence in malignant hepatocytes with a ground-glass appearance in only one needle biopsy specimen of a series of biopsies from 130 consecutive cases of hepatocellular carcinoma. The patient was 14 years old. HBsAg was identified by aldehyde fuchsin stain in nonmalignant hepatocytes of 48 (58%) of 83 biopsy specimens that contained nonmalignant liver tissue. The antigen was demonstrable in significantly greater proportions of cases in younger age groups. A similar but not identical age relationship has been found for hepatitis B antigenemia in Hong Kong. It appears that the ability to produce HBsAg declines with age. The usual absence of demonstrable HBsAg in cells of hepatocellular carcinoma may be due to a failure of this characteristic to survive into the malignant cell line, and so does not invalidate the possibility that the hepatitis B virus (HBV) plays a direct role in the pathogenesis of hepatocellular carcinoma. In exceptional circumstances, as when hepatocellular carcinoma appears at an unusually early age, this marker is identifiable in cells of the tumor.", "contents": "Cytoplasmic hepatitis B surface antigen and the ground-glass appearance in hepatocellular carcinoma. Hepatitis B surface antigen (HBsAg) was identified with aldehyde fuchsin and immunoperoxidase stain and by immunofluorescence in malignant hepatocytes with a ground-glass appearance in only one needle biopsy specimen of a series of biopsies from 130 consecutive cases of hepatocellular carcinoma. The patient was 14 years old. HBsAg was identified by aldehyde fuchsin stain in nonmalignant hepatocytes of 48 (58%) of 83 biopsy specimens that contained nonmalignant liver tissue. The antigen was demonstrable in significantly greater proportions of cases in younger age groups. A similar but not identical age relationship has been found for hepatitis B antigenemia in Hong Kong. It appears that the ability to produce HBsAg declines with age. The usual absence of demonstrable HBsAg in cells of hepatocellular carcinoma may be due to a failure of this characteristic to survive into the malignant cell line, and so does not invalidate the possibility that the hepatitis B virus (HBV) plays a direct role in the pathogenesis of hepatocellular carcinoma. In exceptional circumstances, as when hepatocellular carcinoma appears at an unusually early age, this marker is identifiable in cells of the tumor."}
{"id": "PMID:218446", "title": "Seasonality and the requirements for perpetuation and eradication of viruses in populations.", "content": "Perpetuation of a virus in a population is distinct from the ability to persist in a cell culture or individual host. Parameters which determine perpetuation include: 1) the size of the population; 2) the turnover of the population; 3) the proportion of immunes in the population; 4) the transmissibility of the infection; and 5) the generation time between sequential infections. These parameters may be grouped into two composite factors which most directly affect transmission dynamics and perpetuation: (a) population turnover per generation period, and (b) transmissibility or the fraction of susceptibles infected per existing infection. Perpetuation in small populations usually requires either the ability to persist in individuals or rapid population turnover. Conversely, human viruses which initiate only acute infections require larger populations to persist. Seasonal variation in transmissibility can greatly increase the minimum population size in which persistence is possible, and we argue that the population size of 500,000 for measles persistence (described by Bartlett) is primarily a consequence of seasonal variation. Computer modelling can be used to examine the effect of changes in parameters which determine the seasonal cycle of virus perpetuation and fadeout. Finally, human infections are reviewed to indicate those which have been eradicated (smallpox), are on the threshold of eradication (poliomyelitis), are possibly eradicable (measles), or could be candidates for future efforts (hepatitis A and hepatitis B). In developing a strategy for eradication two points are of great potential utility: first, the seasonal trough should be exploited as a time for effective intervention; and, second, containment efforts should be directed at epidemiologically important population groupings such as schools.", "contents": "Seasonality and the requirements for perpetuation and eradication of viruses in populations. Perpetuation of a virus in a population is distinct from the ability to persist in a cell culture or individual host. Parameters which determine perpetuation include: 1) the size of the population; 2) the turnover of the population; 3) the proportion of immunes in the population; 4) the transmissibility of the infection; and 5) the generation time between sequential infections. These parameters may be grouped into two composite factors which most directly affect transmission dynamics and perpetuation: (a) population turnover per generation period, and (b) transmissibility or the fraction of susceptibles infected per existing infection. Perpetuation in small populations usually requires either the ability to persist in individuals or rapid population turnover. Conversely, human viruses which initiate only acute infections require larger populations to persist. Seasonal variation in transmissibility can greatly increase the minimum population size in which persistence is possible, and we argue that the population size of 500,000 for measles persistence (described by Bartlett) is primarily a consequence of seasonal variation. Computer modelling can be used to examine the effect of changes in parameters which determine the seasonal cycle of virus perpetuation and fadeout. Finally, human infections are reviewed to indicate those which have been eradicated (smallpox), are on the threshold of eradication (poliomyelitis), are possibly eradicable (measles), or could be candidates for future efforts (hepatitis A and hepatitis B). In developing a strategy for eradication two points are of great potential utility: first, the seasonal trough should be exploited as a time for effective intervention; and, second, containment efforts should be directed at epidemiologically important population groupings such as schools."}
{"id": "PMID:218447", "title": "Serologically active clinically quiescent systemic lupus erythematosus: a discordance between clinical and serologic features.", "content": "The significance of abnormal serologic tests in systemic lupus erythematosus (SLE) in the absence of active clinical disease is unclear. In this report we describe a group of 14 patients with SLE in whom a discordance between clinical and serologic features was apparent. These patients had persistently positive lupus erythematosus preparations and antinuclear antibody tests, low serum complement levels and high levels of DNA binding. Their lymphocyte response to concanavalin A (Con A) mitogen was suppressed. They have been asymptomatic and have remained untreated for a mean of four and a quarter years.", "contents": "Serologically active clinically quiescent systemic lupus erythematosus: a discordance between clinical and serologic features. The significance of abnormal serologic tests in systemic lupus erythematosus (SLE) in the absence of active clinical disease is unclear. In this report we describe a group of 14 patients with SLE in whom a discordance between clinical and serologic features was apparent. These patients had persistently positive lupus erythematosus preparations and antinuclear antibody tests, low serum complement levels and high levels of DNA binding. Their lymphocyte response to concanavalin A (Con A) mitogen was suppressed. They have been asymptomatic and have remained untreated for a mean of four and a quarter years."}
{"id": "PMID:218448", "title": "Hormonal hyperthermia: endocrinologic causes of fever.", "content": "Although hyperthermia is a component of many endocrine diseases, it is uncommon for fever to be the presenting manifestation of hormonal disorders. During a four year period we encountered six patients, hospitalized principally because of fever, who were found to have endocrine causes for the fever. In all, the admitting diagnosis was infection; three were suspected of having tuberculosis, two of gram-negative bacteremia and one of endocarditis. Except for asymptomatic bacteriuria in one patient (who remained febrile despite appropriate antibiotic therapy) infection was ruled out in all cases, and fever was attributed to \"masked\" thyrotoxicosis, triiodothyronine (T3) toxicosis, subacute thyroiditis, primary adrenal insufficiency, secondary adrenal insufficiency and pheochromocytoma. In a seventh patient, extreme pyrexia developed in the setting of the thyroid storm. The importance of hormonal mechanisms in thermoregulation is discussed.", "contents": "Hormonal hyperthermia: endocrinologic causes of fever. Although hyperthermia is a component of many endocrine diseases, it is uncommon for fever to be the presenting manifestation of hormonal disorders. During a four year period we encountered six patients, hospitalized principally because of fever, who were found to have endocrine causes for the fever. In all, the admitting diagnosis was infection; three were suspected of having tuberculosis, two of gram-negative bacteremia and one of endocarditis. Except for asymptomatic bacteriuria in one patient (who remained febrile despite appropriate antibiotic therapy) infection was ruled out in all cases, and fever was attributed to \"masked\" thyrotoxicosis, triiodothyronine (T3) toxicosis, subacute thyroiditis, primary adrenal insufficiency, secondary adrenal insufficiency and pheochromocytoma. In a seventh patient, extreme pyrexia developed in the setting of the thyroid storm. The importance of hormonal mechanisms in thermoregulation is discussed."}
{"id": "PMID:218449", "title": "Cytomegalovirus granulomatous hepatitis.", "content": "Three patients with granulomatous hepatitis due to cytomegalovirus are described. They are compared to the three previously described patients with this disease, and their clinical and serologic characteristics are discussed. Similarities and differences between infectious mononucleosis (Epstein-Barr virus) and cytomegalovirus infections are adduced. That cytomegalovirus may be a cause of granulomatous hepatitis in the adult is stressed.", "contents": "Cytomegalovirus granulomatous hepatitis. Three patients with granulomatous hepatitis due to cytomegalovirus are described. They are compared to the three previously described patients with this disease, and their clinical and serologic characteristics are discussed. Similarities and differences between infectious mononucleosis (Epstein-Barr virus) and cytomegalovirus infections are adduced. That cytomegalovirus may be a cause of granulomatous hepatitis in the adult is stressed."}
{"id": "PMID:218452", "title": "Prostaglandin E and hypercalcemia in breast carcinoma: only a tumor marker? A need for perspective.", "content": "Prostaglandin E concentrations were measured in a patiet with breast carcinoma, hypercalcemia, undetectable parathyroid hormone (PTH) and no evidence of bone metastases. Catheterization of the drainage bed of her tumor documented production of E series prostaglandins. Treatment with the largest recommended doses of indomethacin for 10 days failed to lower her plasma prostaglandin E (PGE) concentrations or to correct the hypercalcemia, but it normalized urinary excretion of PGE. Subsequent chemotherapy reduced prostaglandin concentrations toward normal values concomitant with a reduction of clinically estimated tumor burden. During this period of time, serum calcium concentrations had no consistent relationship to the plasma PGE levels. We suggest that PGE merely reflected the tumor burden of this patient and did not directly contribute to the genesis of her hypercalcemia. The pertinent literature relating PGE and hypercalcemia is reviewed.", "contents": "Prostaglandin E and hypercalcemia in breast carcinoma: only a tumor marker? A need for perspective. Prostaglandin E concentrations were measured in a patiet with breast carcinoma, hypercalcemia, undetectable parathyroid hormone (PTH) and no evidence of bone metastases. Catheterization of the drainage bed of her tumor documented production of E series prostaglandins. Treatment with the largest recommended doses of indomethacin for 10 days failed to lower her plasma prostaglandin E (PGE) concentrations or to correct the hypercalcemia, but it normalized urinary excretion of PGE. Subsequent chemotherapy reduced prostaglandin concentrations toward normal values concomitant with a reduction of clinically estimated tumor burden. During this period of time, serum calcium concentrations had no consistent relationship to the plasma PGE levels. We suggest that PGE merely reflected the tumor burden of this patient and did not directly contribute to the genesis of her hypercalcemia. The pertinent literature relating PGE and hypercalcemia is reviewed."}
{"id": "PMID:218453", "title": "Adrenoleukodystrophy and adrenomyeloneuropathy associated with partial adrenal insufficiency in three generations of a kindred.", "content": "Four cases of adrenoleukodystrophy (ALD) and one case of adrenomyeloneuropathy (AMN) have developed in a kindred over three generations demonstrating that AMN is a clinical variant of ALD. Pituitary-adrenal function studies were performed in 10 family members, including two affected males and four females identified as carriers of ALD/AMN. No pituitary-adrenal abnormality was found in the carriers. However, basal morning plasma adrenocorticotropic hormone (ACTH) levels were markedly elevated in the two males with ALD and AMN, despite the fact that they had no clinical signs of adrenal insufficiency and that morning plasma cortisol levels and their response to maximal exogenous ACTH stimulation appeared to be normal. In addition, the integrated 24-hour response to the administration were also subnormal in these two cases. Thus, people with ALD and AMN may have subclinical partial adrenocrotical insufficiency. No other endocrinologic dysfunction was identified.", "contents": "Adrenoleukodystrophy and adrenomyeloneuropathy associated with partial adrenal insufficiency in three generations of a kindred. Four cases of adrenoleukodystrophy (ALD) and one case of adrenomyeloneuropathy (AMN) have developed in a kindred over three generations demonstrating that AMN is a clinical variant of ALD. Pituitary-adrenal function studies were performed in 10 family members, including two affected males and four females identified as carriers of ALD/AMN. No pituitary-adrenal abnormality was found in the carriers. However, basal morning plasma adrenocorticotropic hormone (ACTH) levels were markedly elevated in the two males with ALD and AMN, despite the fact that they had no clinical signs of adrenal insufficiency and that morning plasma cortisol levels and their response to maximal exogenous ACTH stimulation appeared to be normal. In addition, the integrated 24-hour response to the administration were also subnormal in these two cases. Thus, people with ALD and AMN may have subclinical partial adrenocrotical insufficiency. No other endocrinologic dysfunction was identified."}
{"id": "PMID:218455", "title": "Adrenocorticotropin and glucocorticoid concentrations in fetal and maternal plasma of rabbit does continuously infused with cortisol from day 21 to day 24 of gestation.", "content": "Previous studies have suggested that suppression of fetal rabbit adrenocorticotropin (ACTH) secretion results in impaired development of ACTH-specific adenylate cyclase activity. In order to test this hypothesis we measured fetal and maternal plasma ACTH, cortisol, and corticosterone concentrations in control does and does infused with 0.3 mg of cortisol/hour at 21 to 24 days of gestation. This cortisol infusion regimen significantly depressed maternal and fetal plasma ACTH and corticosterone concentrations but did not change fetal serum cortisol concentrations. These findings further support the hypothesis that fetal ACTH plays a role in the normal development of the adenylate cyclase catalytic portion of the ACTH receptor complex and adrenal differentiation during this critical period of fetal life.", "contents": "Adrenocorticotropin and glucocorticoid concentrations in fetal and maternal plasma of rabbit does continuously infused with cortisol from day 21 to day 24 of gestation. Previous studies have suggested that suppression of fetal rabbit adrenocorticotropin (ACTH) secretion results in impaired development of ACTH-specific adenylate cyclase activity. In order to test this hypothesis we measured fetal and maternal plasma ACTH, cortisol, and corticosterone concentrations in control does and does infused with 0.3 mg of cortisol/hour at 21 to 24 days of gestation. This cortisol infusion regimen significantly depressed maternal and fetal plasma ACTH and corticosterone concentrations but did not change fetal serum cortisol concentrations. These findings further support the hypothesis that fetal ACTH plays a role in the normal development of the adenylate cyclase catalytic portion of the ACTH receptor complex and adrenal differentiation during this critical period of fetal life."}
{"id": "PMID:218456", "title": "Desoxycorticosterone in normal pregnancy. II. Cortisol-dependent fluctuations in free plasma desoxycorticosterone.", "content": "Desoxycorticosterone (DOC) secretion increases during pregnancy. Administration of adrenocorticotropic hormone (ACTH) to women during the third trimester of pregnancy was noted previously to result in marked sodium retention, while aldosterone excretion declined. Since urinary tetrahydrodesoxycorticosterone increased substantially, sodium retention resulting from ACTH was ascribed to enhanced DOC secretion. Surprisingly, the elevated plasma DOC in late pregnancy failed to respond consistently to ACTH. Effects of ACTH upon total plasma concentrations and free indexes of DOC and cortisol were studied in pregnant women in the third trimester. As a result of ACTH, plasma cortisol and the free cortisol index increased strikingly; the plasma free DOC index rose markedly in those subjects in whom the total plasma DOC level was not altered appreciably and was unchanged or even increased slightly in the few subjects in whom the total DOC level decreased. The results support the proposition that the plasma free DOC fraction is increased because of displacement from corticosteroid-binding globulin by the ACTH-induced increment in cortisol. Resultant elevations of free DOC would not be evident from customary measurements of the total DOC concentration but, nonetheless, could contribute to sodium retention and also would be available for hepatic metabolism.", "contents": "Desoxycorticosterone in normal pregnancy. II. Cortisol-dependent fluctuations in free plasma desoxycorticosterone. Desoxycorticosterone (DOC) secretion increases during pregnancy. Administration of adrenocorticotropic hormone (ACTH) to women during the third trimester of pregnancy was noted previously to result in marked sodium retention, while aldosterone excretion declined. Since urinary tetrahydrodesoxycorticosterone increased substantially, sodium retention resulting from ACTH was ascribed to enhanced DOC secretion. Surprisingly, the elevated plasma DOC in late pregnancy failed to respond consistently to ACTH. Effects of ACTH upon total plasma concentrations and free indexes of DOC and cortisol were studied in pregnant women in the third trimester. As a result of ACTH, plasma cortisol and the free cortisol index increased strikingly; the plasma free DOC index rose markedly in those subjects in whom the total plasma DOC level was not altered appreciably and was unchanged or even increased slightly in the few subjects in whom the total DOC level decreased. The results support the proposition that the plasma free DOC fraction is increased because of displacement from corticosteroid-binding globulin by the ACTH-induced increment in cortisol. Resultant elevations of free DOC would not be evident from customary measurements of the total DOC concentration but, nonetheless, could contribute to sodium retention and also would be available for hepatic metabolism."}
{"id": "PMID:218457", "title": "In vitro stimulation of human colostral lymphocytes by cytomegalovirus.", "content": "Lymphocytes isolated from the peripheral blood and colostrum of 17 healthy donors, 1 to 3 days post partum, were cultured with cytomegalovirus (CMV), strain AD169, as stimulating antigen in a lymphocyte transformation test. The test was performed in microculture utilizing the cell-free supernatant of CMV-infected human fibroblasts and isolated peripheral blood and colostral lymphocytes showing normal reactivity to phytohemagglutinin. Lymphocytes from CMV-seropositive donors were stimulated by the CMV antigen, whereas lymphocytes from both male and female CMV-seronegative donors failed to respond, as measured by incorporation of tritiated thymidine. In those donors from whom utilizable colostrum samples were obtained, two donors lacking peripheral blood lymphocyte (PBL) CMV reactivity also lacked colostral lymphocyte CMV reactivity. The remaining five colostrum donors showed both PBL and colostral lymphocyte reactivity to the CMV antigen, with colostral lymphocyte reactivity in four of five donors exceeding PBL-cytomegalovirus reactivity. There was no clear-cut correlation between the titer of CMV antibody by complement fixation and the amount of tritiated thymidine incorporated into the lymphocytes stimulated with the CMV antigen. These results highlight current knowledge that milk and colostrum contain large numbers of specifically sensitized T-lymphocytes, expressing a selective quota of maternal cell-mediated immunities. We are currently investigating the possibility that CMV-reactive colostral lymphocytes obtained during suckling may be of some protective value to the immunologically inexperienced neonate by transferring an adoptive immunity. This assumes special significance in the light of known transmission of CMV via mothers' milk to neonates.", "contents": "In vitro stimulation of human colostral lymphocytes by cytomegalovirus. Lymphocytes isolated from the peripheral blood and colostrum of 17 healthy donors, 1 to 3 days post partum, were cultured with cytomegalovirus (CMV), strain AD169, as stimulating antigen in a lymphocyte transformation test. The test was performed in microculture utilizing the cell-free supernatant of CMV-infected human fibroblasts and isolated peripheral blood and colostral lymphocytes showing normal reactivity to phytohemagglutinin. Lymphocytes from CMV-seropositive donors were stimulated by the CMV antigen, whereas lymphocytes from both male and female CMV-seronegative donors failed to respond, as measured by incorporation of tritiated thymidine. In those donors from whom utilizable colostrum samples were obtained, two donors lacking peripheral blood lymphocyte (PBL) CMV reactivity also lacked colostral lymphocyte CMV reactivity. The remaining five colostrum donors showed both PBL and colostral lymphocyte reactivity to the CMV antigen, with colostral lymphocyte reactivity in four of five donors exceeding PBL-cytomegalovirus reactivity. There was no clear-cut correlation between the titer of CMV antibody by complement fixation and the amount of tritiated thymidine incorporated into the lymphocytes stimulated with the CMV antigen. These results highlight current knowledge that milk and colostrum contain large numbers of specifically sensitized T-lymphocytes, expressing a selective quota of maternal cell-mediated immunities. We are currently investigating the possibility that CMV-reactive colostral lymphocytes obtained during suckling may be of some protective value to the immunologically inexperienced neonate by transferring an adoptive immunity. This assumes special significance in the light of known transmission of CMV via mothers' milk to neonates."}
{"id": "PMID:218459", "title": "Reproductive function in aged female chimpanzees.", "content": "Reproductive function was evaluated in ten female chimpanzees (Pan troglodytes) aged 35-48 years. Forty-eight years is the longevity record for the chimpanzee. Data on cycle frequency and duration was available for seven animals. Most were cycling regularly until death, and all had experienced at least one menstrual cycle within one year of death. After exclusion of periods when the animals were pregnant or in postpartum amenorrhea, the mean cycle frequency (+/- standard error)/year was 9.54 +/- 0.20 in seven animals aged 15-25 (432 cycles analyzed) compared to 8.6 +/- 0.76 in the same animals at age 35 + years (405 cycles analyzed); this effect approached significance (p = 0.072, Mann-Whitney U-test). Cycle length of 16 cycles in each of seven animals aged 15-25 was 32.23 +/- 0.38 days. The same animals when aged over 35 had mean cycle lengths of 35.59 +/- 0.73. This difference was not significant, although cycle lengths clearly increased with age in some individual animals. In five aged animals for which mating data was available, appropriate exposure to a male occurred in 52 cycles, but only two pregnancies occurred; one pregnancy resulted in a live birth at age 38, the other in a stillbirth at age 40. This conception rate was 3.85% compared with 20% in the same animals aged 15-25. These data suggest greatly reduced fertility after age 35, although menstrual cycle frequency remained high. The persistence of menstrual cyclicity until death, which occurred due to natural causes at latest in the fifth decade, is in striking contrast to the human female in which menopause occurs in the fifth decade and death is often postponed for several more decades.", "contents": "Reproductive function in aged female chimpanzees. Reproductive function was evaluated in ten female chimpanzees (Pan troglodytes) aged 35-48 years. Forty-eight years is the longevity record for the chimpanzee. Data on cycle frequency and duration was available for seven animals. Most were cycling regularly until death, and all had experienced at least one menstrual cycle within one year of death. After exclusion of periods when the animals were pregnant or in postpartum amenorrhea, the mean cycle frequency (+/- standard error)/year was 9.54 +/- 0.20 in seven animals aged 15-25 (432 cycles analyzed) compared to 8.6 +/- 0.76 in the same animals at age 35 + years (405 cycles analyzed); this effect approached significance (p = 0.072, Mann-Whitney U-test). Cycle length of 16 cycles in each of seven animals aged 15-25 was 32.23 +/- 0.38 days. The same animals when aged over 35 had mean cycle lengths of 35.59 +/- 0.73. This difference was not significant, although cycle lengths clearly increased with age in some individual animals. In five aged animals for which mating data was available, appropriate exposure to a male occurred in 52 cycles, but only two pregnancies occurred; one pregnancy resulted in a live birth at age 38, the other in a stillbirth at age 40. This conception rate was 3.85% compared with 20% in the same animals aged 15-25. These data suggest greatly reduced fertility after age 35, although menstrual cycle frequency remained high. The persistence of menstrual cyclicity until death, which occurred due to natural causes at latest in the fifth decade, is in striking contrast to the human female in which menopause occurs in the fifth decade and death is often postponed for several more decades."}
{"id": "PMID:218460", "title": "Thyroxine and Na+ transport in toad: role in transition from poikilo- to homeothermy.", "content": "The effects of thyroxine (T4) on Na+ transport, oxygen consumption (QO2), and Na+-K+-ATPase activity were studied in the urinary bladder and liver of the toad Bufo marinus. In the bladder, T4 in vitro (10(-8) to 10(-6) M) had no significant effect on these parameters during 15 h of incubation. When injected intraperitoneally (approximately 20 microgram/(kg body wt.day) for 6 days), T4 lowered base-line, short-circuit current by 62% (P less than 0.0025) and potential difference by 37% (P less than 0.001), increasing tissue resistance by 40% (P less than 0.02). T4 depressed QO2/DNA (-25%, P less than 0.05) with no significant effect on Na+-K+-ATPase activity. In liver, T4 increased the recovery per cell DNA of mitochondrial proteins by 32% (P less than 0.025), corresponding to an increased QO2 (stage IV) of isolated mitochondria per cell DNA (+54%, P less than 0.01). There was no significant effect on Na+-K+-ATPase activity. These results suggest that, unlike its function in the rat, T4 in the toad does not regulate cellular thermogenesis by inducing Na+-K+-ATPase. This major difference could account at least in part for the transition from poikilothermy to homeothermy. In addition, T4 has a distinct inhibitory effect on Na+ transport in the urinary bladder, which suggests an antagonism to the action of aldosterone.", "contents": "Thyroxine and Na+ transport in toad: role in transition from poikilo- to homeothermy. The effects of thyroxine (T4) on Na+ transport, oxygen consumption (QO2), and Na+-K+-ATPase activity were studied in the urinary bladder and liver of the toad Bufo marinus. In the bladder, T4 in vitro (10(-8) to 10(-6) M) had no significant effect on these parameters during 15 h of incubation. When injected intraperitoneally (approximately 20 microgram/(kg body wt.day) for 6 days), T4 lowered base-line, short-circuit current by 62% (P less than 0.0025) and potential difference by 37% (P less than 0.001), increasing tissue resistance by 40% (P less than 0.02). T4 depressed QO2/DNA (-25%, P less than 0.05) with no significant effect on Na+-K+-ATPase activity. In liver, T4 increased the recovery per cell DNA of mitochondrial proteins by 32% (P less than 0.025), corresponding to an increased QO2 (stage IV) of isolated mitochondria per cell DNA (+54%, P less than 0.01). There was no significant effect on Na+-K+-ATPase activity. These results suggest that, unlike its function in the rat, T4 in the toad does not regulate cellular thermogenesis by inducing Na+-K+-ATPase. This major difference could account at least in part for the transition from poikilothermy to homeothermy. In addition, T4 has a distinct inhibitory effect on Na+ transport in the urinary bladder, which suggests an antagonism to the action of aldosterone."}
{"id": "PMID:218461", "title": "Time course of the T3- and T4-induced increase in rat soleus muscle mitochondria.", "content": "Citrate synthase and cytochrome c increase in soleus muscle of rats in response to excess thyroid hormones. The half times of the increase in the levels of citrate synthase and cytochrome c in soleus muscle during induction are greater than the half times of the decline in enzyme levels after cessation of treatment (15 days vs. 7 days for citrate synthase). Denervation of the soleus does not prevent the increase in citrate synthase in response to thyrotoxicosis. This provides evidence that thyroid hormones affect the muscle directly and not via the motor nerves. ATP concentration is reduced in liver, but not in soleus muscle in response to thyrotoxicosis. Creatine phosphate is not significantly altered in soleus muscle. Cyclic AMP is slightly lower in thyrotoxic soleus muscle. Simultaneous treatment with thyroid hormones and propranolol does not affect the increase in citrate synthase in response to excess thyroid hormones. It is concluded that the increase in muscle mitochondria associated with thyrotoxicosis is not mediated via the nervous system or by a cAMP-regulated process.", "contents": "Time course of the T3- and T4-induced increase in rat soleus muscle mitochondria. Citrate synthase and cytochrome c increase in soleus muscle of rats in response to excess thyroid hormones. The half times of the increase in the levels of citrate synthase and cytochrome c in soleus muscle during induction are greater than the half times of the decline in enzyme levels after cessation of treatment (15 days vs. 7 days for citrate synthase). Denervation of the soleus does not prevent the increase in citrate synthase in response to thyrotoxicosis. This provides evidence that thyroid hormones affect the muscle directly and not via the motor nerves. ATP concentration is reduced in liver, but not in soleus muscle in response to thyrotoxicosis. Creatine phosphate is not significantly altered in soleus muscle. Cyclic AMP is slightly lower in thyrotoxic soleus muscle. Simultaneous treatment with thyroid hormones and propranolol does not affect the increase in citrate synthase in response to excess thyroid hormones. It is concluded that the increase in muscle mitochondria associated with thyrotoxicosis is not mediated via the nervous system or by a cAMP-regulated process."}
{"id": "PMID:218464", "title": "Induction of delta-aminolevulinic acid synthetase in muscle by exercise or thyroxine.", "content": "There is evidence that delta-aminolevulinic acid (ALA) synthetase is the rate-limiting enzyme in heme biosynthesis. Accumulation of the apoproteins of the mitochondrial cytochromes appears to be regulated by availability of heme. Exercise and thyrotoxicosis bring about increases in the cytochromes, and in other mitochondrial enzymes, in muscle. In this context, we have examined the effects of exercise and of thyroid hormones on ALA synthetase activity in skeletal muscle. Treadmill running and injection of thyroid hormones both resulted in significant increases in muscle ALA synthetase activity. A rise in ALA synthetase activity was evident within 17 h after a bout of vigorous exercise and 14 h after a single injection of thyroid hormones. The increase in ALA synthetase preceded the increase in cytochrome c, which was used as a mitochondrial marker. These results are compatible with the hypothesis that a relationship exists between heme synthesis and mitochondrial growth in which the rate-controlling step is ALA synthetase activity.", "contents": "Induction of delta-aminolevulinic acid synthetase in muscle by exercise or thyroxine. There is evidence that delta-aminolevulinic acid (ALA) synthetase is the rate-limiting enzyme in heme biosynthesis. Accumulation of the apoproteins of the mitochondrial cytochromes appears to be regulated by availability of heme. Exercise and thyrotoxicosis bring about increases in the cytochromes, and in other mitochondrial enzymes, in muscle. In this context, we have examined the effects of exercise and of thyroid hormones on ALA synthetase activity in skeletal muscle. Treadmill running and injection of thyroid hormones both resulted in significant increases in muscle ALA synthetase activity. A rise in ALA synthetase activity was evident within 17 h after a bout of vigorous exercise and 14 h after a single injection of thyroid hormones. The increase in ALA synthetase preceded the increase in cytochrome c, which was used as a mitochondrial marker. These results are compatible with the hypothesis that a relationship exists between heme synthesis and mitochondrial growth in which the rate-controlling step is ALA synthetase activity."}
{"id": "PMID:218465", "title": "Some aspects of temperature regulation in newborn harp seal pups.", "content": "Harp seals are born on the drifting ice of the North Atlantic Ocean during arctic winter when temperatures of -20 degrees C, occasionally in combination with wind of 10 m/s, might prevail for days. At birth the pups lack subcutaneous blubber and the wet infantile fur has a conductance value of 30.0 W . m-2 . degrees C-1, as compared with only 2.0 W . m-2 . degrees C-1 when dry. While still wet immediately after birth the pups are nevertheless able to retain body core temperature by shivering. This activity leads to reduction of muscle fat and glycogen stores. Nonshivering thermogenesis commences in thermogenic adipose tissue by virtue of loosely coupled mitochondria. Thermogenic adipose tissue is found at birth both as a subcutaneous layer along the back and as internal deposits around venous plexuses in the neck, on the pericardium, on the kidneys, and the abdominal walls. After about 3 days of suckling the subcutaneous adipose tissue loses its thermogenic function being gradually transformed into blubber, whereas the internal deposits persist at least until the pups venture into water at the age of 3-4 wk.", "contents": "Some aspects of temperature regulation in newborn harp seal pups. Harp seals are born on the drifting ice of the North Atlantic Ocean during arctic winter when temperatures of -20 degrees C, occasionally in combination with wind of 10 m/s, might prevail for days. At birth the pups lack subcutaneous blubber and the wet infantile fur has a conductance value of 30.0 W . m-2 . degrees C-1, as compared with only 2.0 W . m-2 . degrees C-1 when dry. While still wet immediately after birth the pups are nevertheless able to retain body core temperature by shivering. This activity leads to reduction of muscle fat and glycogen stores. Nonshivering thermogenesis commences in thermogenic adipose tissue by virtue of loosely coupled mitochondria. Thermogenic adipose tissue is found at birth both as a subcutaneous layer along the back and as internal deposits around venous plexuses in the neck, on the pericardium, on the kidneys, and the abdominal walls. After about 3 days of suckling the subcutaneous adipose tissue loses its thermogenic function being gradually transformed into blubber, whereas the internal deposits persist at least until the pups venture into water at the age of 3-4 wk."}
{"id": "PMID:218466", "title": "Physical activity and plasma cyclic adenosine monophosphate levels in manic-depressive patients and healthy adults.", "content": "Intense exercise for one hour induced a significant increase in plasma cyclic adenosine monophosphate (cAMP) in 5 healthy volunteers. In 44 manic-depressive patients, cAMP levels correlated more strongly with mood ratings than with activity scores. The authors conclude that physical activity is one of the factors which contribute to changes of cAMP levels in affective illness.", "contents": "Physical activity and plasma cyclic adenosine monophosphate levels in manic-depressive patients and healthy adults. Intense exercise for one hour induced a significant increase in plasma cyclic adenosine monophosphate (cAMP) in 5 healthy volunteers. In 44 manic-depressive patients, cAMP levels correlated more strongly with mood ratings than with activity scores. The authors conclude that physical activity is one of the factors which contribute to changes of cAMP levels in affective illness."}
{"id": "PMID:218467", "title": "A possible cardiovascular effect of lithium.", "content": "Heart rate rises associated with performance of mental arithmetic tasks were compared in 22 euthymic manic-depressive patients receiving lithium carbonate and 17 drug-free normal controls. The lithium-treated subjects showed a markedly lower heart rate response to the mental arithmetic stimulus. No effect was observed on basal heart rate. The results are consistent with lithium's reported inhibition of noradrenaline-induced rises in adenylate cyclase activity but lack of inhibition of basal adenylate cyclase activity. The biochemical and psychophysiological findings may parallel lithium's unique ability to calm excited behavior without sedating normal behavior.", "contents": "A possible cardiovascular effect of lithium. Heart rate rises associated with performance of mental arithmetic tasks were compared in 22 euthymic manic-depressive patients receiving lithium carbonate and 17 drug-free normal controls. The lithium-treated subjects showed a markedly lower heart rate response to the mental arithmetic stimulus. No effect was observed on basal heart rate. The results are consistent with lithium's reported inhibition of noradrenaline-induced rises in adenylate cyclase activity but lack of inhibition of basal adenylate cyclase activity. The biochemical and psychophysiological findings may parallel lithium's unique ability to calm excited behavior without sedating normal behavior."}
{"id": "PMID:218469", "title": "Adenoid cystic carcinoma of the salivary glands. A study of ninety-three cases.", "content": "The present study reviews ninety-three cases of adenoid cystic carcinoma of the major (80 cases) and minor (13 cases) salivary glands occuring in ninety-one patients. This tumor is insidious in its presentation and subsequent clinical course with early perineural lymphatic invasion and late metastases. Many patients remain alive but with recurrent disease. The high incidence of recurrent disease (parotid gland 20 of 47, submaxillary gland 20 of 33, and minor salivary glands 7 of 11) suggests inadequate initial surgery at all anatomic sites. Misdiagnosis (16 cases) on frozen or permanent section has led to less than optimum primary treatment. The frequency of perineural lymphatic involvement with recurrence (11 of 19 cases) suggests that the tumor may be extending along the nerve roots in an anatomic area with extensive nerve distribution (the head and neck). Radical neck dissection, in our studies, has contributed to improved survival rates when the primary site has been the submaxillary gland. The treatment of recurrent disease has been primarily surgical (3 operations per patient), and palliation with prolonged survival has been achieved with radical excision of recurrence. The fifteen year determinate cure rate of 19 per cent in comparable to that reported in the world literature. Radiation therapy has been helpful in palliation but has not been curative. Radiation treatment was used for recurrence in twenty-seven patients, and the average time from radiation treatment to death was 3.8 years.", "contents": "Adenoid cystic carcinoma of the salivary glands. A study of ninety-three cases. The present study reviews ninety-three cases of adenoid cystic carcinoma of the major (80 cases) and minor (13 cases) salivary glands occuring in ninety-one patients. This tumor is insidious in its presentation and subsequent clinical course with early perineural lymphatic invasion and late metastases. Many patients remain alive but with recurrent disease. The high incidence of recurrent disease (parotid gland 20 of 47, submaxillary gland 20 of 33, and minor salivary glands 7 of 11) suggests inadequate initial surgery at all anatomic sites. Misdiagnosis (16 cases) on frozen or permanent section has led to less than optimum primary treatment. The frequency of perineural lymphatic involvement with recurrence (11 of 19 cases) suggests that the tumor may be extending along the nerve roots in an anatomic area with extensive nerve distribution (the head and neck). Radical neck dissection, in our studies, has contributed to improved survival rates when the primary site has been the submaxillary gland. The treatment of recurrent disease has been primarily surgical (3 operations per patient), and palliation with prolonged survival has been achieved with radical excision of recurrence. The fifteen year determinate cure rate of 19 per cent in comparable to that reported in the world literature. Radiation therapy has been helpful in palliation but has not been curative. Radiation treatment was used for recurrence in twenty-seven patients, and the average time from radiation treatment to death was 3.8 years."}
{"id": "PMID:218470", "title": "Elective hepatic resection.", "content": "Significant salvage of patients with a wide variety of cysts and benign tumors of the liver and of some patients with biliary strictures can be achieved by hepatic resection in carefully selected clinical situations with a low operative mortality rate and an acceptable postoperative complication rate. Still to be determined is the role of hepatic resection in metastatic carcinoma and sarcoma of the liver, where survival is modest but measurable, but important palliation can be achieved. Hepatomas should be resected when possible, but hepatic resection for aid in resection of bile duct carcinoma has proved generally unrewarding.", "contents": "Elective hepatic resection. Significant salvage of patients with a wide variety of cysts and benign tumors of the liver and of some patients with biliary strictures can be achieved by hepatic resection in carefully selected clinical situations with a low operative mortality rate and an acceptable postoperative complication rate. Still to be determined is the role of hepatic resection in metastatic carcinoma and sarcoma of the liver, where survival is modest but measurable, but important palliation can be achieved. Hepatomas should be resected when possible, but hepatic resection for aid in resection of bile duct carcinoma has proved generally unrewarding."}
{"id": "PMID:218471", "title": "Fluidity and lipid composition of mouse biomembranes during adaptation to ethanol.", "content": "Showing that ethanol added in vitro increased the fluidity of mouse erythrocyte and synaptosomal membranes and that the same membranes isolated from mice after chronic treatment with ethanol had increased cholesterol and were resistant to ethanol in vitro, the study suggests that the animals had adapted to the chronic presence of the drug by changing their membrane lipid composition to offset the fluidizing effects of ethanol.", "contents": "Fluidity and lipid composition of mouse biomembranes during adaptation to ethanol. Showing that ethanol added in vitro increased the fluidity of mouse erythrocyte and synaptosomal membranes and that the same membranes isolated from mice after chronic treatment with ethanol had increased cholesterol and were resistant to ethanol in vitro, the study suggests that the animals had adapted to the chronic presence of the drug by changing their membrane lipid composition to offset the fluidizing effects of ethanol."}
{"id": "PMID:218472", "title": "Chronic degeneration of aminergic nerve endings and blood-aqueous barrier.", "content": "Chemical sympathectomy of the anterior segment of the eye was performed in rabbits with 6-hydroxydopamine (6-OHDA) intravitreously injected. The response of the pupillary diameter (PD) and intraocular pressure (IOP) to NE, E and Isoproterenol was determined through instillation of the drugs in the pretreated and control eyes. The results were as follows: 1) Both PD and IOP at different intervals of time from the injection show a sharp decrease in the treated eye. 2) About four weeks after the injection, the instillation of NE and E increases the PD only in the 6-OHDA pretreated eyes, while IP administration is not effective on both control and pretreated eyes. 3) The instillation of the three drugs, while decreasing IOP in the control eyes, does not modify the already low IOP in the pretreated eyes. The authors suggest the presence of a postdenervation supersensitivity affecting only the alpha receptors, since the beta stimulant IP is inactive in both treated and untreated eyes.", "contents": "Chronic degeneration of aminergic nerve endings and blood-aqueous barrier. Chemical sympathectomy of the anterior segment of the eye was performed in rabbits with 6-hydroxydopamine (6-OHDA) intravitreously injected. The response of the pupillary diameter (PD) and intraocular pressure (IOP) to NE, E and Isoproterenol was determined through instillation of the drugs in the pretreated and control eyes. The results were as follows: 1) Both PD and IOP at different intervals of time from the injection show a sharp decrease in the treated eye. 2) About four weeks after the injection, the instillation of NE and E increases the PD only in the 6-OHDA pretreated eyes, while IP administration is not effective on both control and pretreated eyes. 3) The instillation of the three drugs, while decreasing IOP in the control eyes, does not modify the already low IOP in the pretreated eyes. The authors suggest the presence of a postdenervation supersensitivity affecting only the alpha receptors, since the beta stimulant IP is inactive in both treated and untreated eyes."}
{"id": "PMID:218476", "title": "The occurrence of uterine stromal and intraepithelial monocytes and heterophils during normal late pregnancy in the rat.", "content": "The steady decline in plasma progesterone level that occurs during the last week of pregnancy in the normal rat (Wiest, '70) provides good opportunity to study the effect of withdrawal of progesterone on uterine differentiation. Evidence is presented that tissue monocytes, heterophils, and eosinophils are regular components of the normal late gestational uterus and that their number increases as term approaches. Uterine monocytes and heterophils are located in the endometrial and myometrial stroma as well as within the basal intercellular compartment of the luminal epithelium. Stromal monocytes are distributed throughout the attenuated endometrium of late gestation, but are more common immediately beneath the luminal epithelium. In the myometrium, monocytes and heterophils occur, often as perivascular, clusters in the connective tissue septum that separates the two layers of smooth muscle. Eosinophils are present especially in the deep endometrial and myometrial stroma, and increase in number as plasma estrogen rises immediately before parturition. A small population of lymphocytes is regularly present. An important feature of the prepartum uterine stroma is the sparseness of macrophages. Near term, however, the beginnings of monocytic-macrophagic transformation are noticeable as the cell surface becomes more irregular and organelles associated with endocytic activity arise. The prepartum monocytes are positioned in the same histological sites that during the postpartum period of regression will be occupied by macrophages (Padykula and Campbell, '76). Since it is generally accepted that monocytes are precursors of macrophages, this spatial correlation raises the possibility that cellular preparations for regression commence before birth. The possible significance of prepartum monocytic infiltration is discussed in relation to the effect of changing plasma and uterine concentrations of progesterone on uterine collagenase activity. The steady increase in uterine leucocytes which occurs concomitantly with decreasing uterine binding capacity for progesterone supports the hypothesis by Siiteri et al. ('77) that progesterone in high local concentrations has an anti-inflammatory effect.", "contents": "The occurrence of uterine stromal and intraepithelial monocytes and heterophils during normal late pregnancy in the rat. The steady decline in plasma progesterone level that occurs during the last week of pregnancy in the normal rat (Wiest, '70) provides good opportunity to study the effect of withdrawal of progesterone on uterine differentiation. Evidence is presented that tissue monocytes, heterophils, and eosinophils are regular components of the normal late gestational uterus and that their number increases as term approaches. Uterine monocytes and heterophils are located in the endometrial and myometrial stroma as well as within the basal intercellular compartment of the luminal epithelium. Stromal monocytes are distributed throughout the attenuated endometrium of late gestation, but are more common immediately beneath the luminal epithelium. In the myometrium, monocytes and heterophils occur, often as perivascular, clusters in the connective tissue septum that separates the two layers of smooth muscle. Eosinophils are present especially in the deep endometrial and myometrial stroma, and increase in number as plasma estrogen rises immediately before parturition. A small population of lymphocytes is regularly present. An important feature of the prepartum uterine stroma is the sparseness of macrophages. Near term, however, the beginnings of monocytic-macrophagic transformation are noticeable as the cell surface becomes more irregular and organelles associated with endocytic activity arise. The prepartum monocytes are positioned in the same histological sites that during the postpartum period of regression will be occupied by macrophages (Padykula and Campbell, '76). Since it is generally accepted that monocytes are precursors of macrophages, this spatial correlation raises the possibility that cellular preparations for regression commence before birth. The possible significance of prepartum monocytic infiltration is discussed in relation to the effect of changing plasma and uterine concentrations of progesterone on uterine collagenase activity. The steady increase in uterine leucocytes which occurs concomitantly with decreasing uterine binding capacity for progesterone supports the hypothesis by Siiteri et al. ('77) that progesterone in high local concentrations has an anti-inflammatory effect."}
{"id": "PMID:218477", "title": "Formation of concentric saccules in murine parietal cells after injection of diazo-oxo-norleucine.", "content": "After treatment with various chemical and physical agents, flattened or ring-like saccules may occur in the cytoplasm of parietal cells of the gastric glands of several species of mammals. In the current investigation, similar structures appeared after treatment with high dosages of diazo-oxo-norleucine (DON), a glutamine antagonist. A tentative sequence for their formation is suggested. Saccules formed of unit membrane became abundant in some parietal cells of the treated mice. Single saccules often had narrow lumens and peripheral distensions. The saccules, either singular or several stacked together, became progressively more curved, enclosing a region of cytoplasm that often contained glycogen-like particles and occasionally vesicles or other organelles. Many of the concentric saccules were close to an intracellular canaliculus. Membrane bound cytoplasm containing glycogen-like particles occasionally occurred in the canaliculi, suggesting that exocytosis had occurred. Cytochemistry revealed that glycoproteins were associated with the concentric saccules, probably located on the luminal surface. The glycogen-like particles in all locations stained in a manner characteristic of glycogen. It is suggested that the concentric saccules may form from vesicles of the tubulovesicular system.", "contents": "Formation of concentric saccules in murine parietal cells after injection of diazo-oxo-norleucine. After treatment with various chemical and physical agents, flattened or ring-like saccules may occur in the cytoplasm of parietal cells of the gastric glands of several species of mammals. In the current investigation, similar structures appeared after treatment with high dosages of diazo-oxo-norleucine (DON), a glutamine antagonist. A tentative sequence for their formation is suggested. Saccules formed of unit membrane became abundant in some parietal cells of the treated mice. Single saccules often had narrow lumens and peripheral distensions. The saccules, either singular or several stacked together, became progressively more curved, enclosing a region of cytoplasm that often contained glycogen-like particles and occasionally vesicles or other organelles. Many of the concentric saccules were close to an intracellular canaliculus. Membrane bound cytoplasm containing glycogen-like particles occasionally occurred in the canaliculi, suggesting that exocytosis had occurred. Cytochemistry revealed that glycoproteins were associated with the concentric saccules, probably located on the luminal surface. The glycogen-like particles in all locations stained in a manner characteristic of glycogen. It is suggested that the concentric saccules may form from vesicles of the tubulovesicular system."}
{"id": "PMID:218479", "title": "Intramammary granular cell myoblastoma.", "content": "Two female patients, age 15 and 21 years, with intramammary granular cell myoblastoma who were without recurrence of the development of additional lesions after one year and eight years, nine months respectively, are reported. Electron microscopic examination of one of our cases disclosed the typical osomphilic granules but no features to support a particular cell of origin. Review of the 52 previously reported cases indicates that this unusual intramammary neoplasm has been encountered with relatively few exceptions in the 20 to 59 year age group and in the upper quadrants. It clinically mimics fibroadenoma or carcinoma and on frozen section examination may be misinterpreted as malignant. None have recurred following adequate excision.", "contents": "Intramammary granular cell myoblastoma. Two female patients, age 15 and 21 years, with intramammary granular cell myoblastoma who were without recurrence of the development of additional lesions after one year and eight years, nine months respectively, are reported. Electron microscopic examination of one of our cases disclosed the typical osomphilic granules but no features to support a particular cell of origin. Review of the 52 previously reported cases indicates that this unusual intramammary neoplasm has been encountered with relatively few exceptions in the 20 to 59 year age group and in the upper quadrants. It clinically mimics fibroadenoma or carcinoma and on frozen section examination may be misinterpreted as malignant. None have recurred following adequate excision."}
{"id": "PMID:218481", "title": "Angiotensin-I-converting enzyme and gallium scan in noninvasive evaluation of sarcoidosis.", "content": "Angiotensin-converting enzyme assays and gallium-scan results were obtained from 27 patients with biopsy-proven, clinically active sarcoidosis. Twenty-three of these patients had elevated converting enzyme levels, and 22 had positive gallium-scan results. Three of four patients with normal or borderline-elevated levels of angiotensin-converting enzyme also had positive gallium-scan results. Of 156 nonsarcoid patients (pulmonary and other diseases), 27 were found to have elevated serum converting enzyme levels, and 25 of these had negative gallium-scan results. These results indicate that the combination of an assay of angiotensin-converting enzyme and gallium scan increases diagnostic specificity from 83% to 99% without sacrificing sensitivity. We conclude that the concurrent use of angiotensin-converting enzyme assay and gallium scan is of value in the diagnosis of sarcoidosis.", "contents": "Angiotensin-I-converting enzyme and gallium scan in noninvasive evaluation of sarcoidosis. Angiotensin-converting enzyme assays and gallium-scan results were obtained from 27 patients with biopsy-proven, clinically active sarcoidosis. Twenty-three of these patients had elevated converting enzyme levels, and 22 had positive gallium-scan results. Three of four patients with normal or borderline-elevated levels of angiotensin-converting enzyme also had positive gallium-scan results. Of 156 nonsarcoid patients (pulmonary and other diseases), 27 were found to have elevated serum converting enzyme levels, and 25 of these had negative gallium-scan results. These results indicate that the combination of an assay of angiotensin-converting enzyme and gallium scan increases diagnostic specificity from 83% to 99% without sacrificing sensitivity. We conclude that the concurrent use of angiotensin-converting enzyme assay and gallium scan is of value in the diagnosis of sarcoidosis."}
{"id": "PMID:218482", "title": "Primary aldosteronism: diagnosis, localization, and treatment.", "content": "New diagnostic techniques have enhanced the detection of primary aldosteronism. However, the response of blood pressure after operation in unilateral and bilateral adrenal disease is different. We have compared four localizing techniques--adrenal venography, adrenal isotopic scanning, a modified adrenal venous sampling for steroid measurements, and the anomalous postural decrease in plasma aldosterone concentration--in 51 patients with primary aldosteronism, all of whom had undergone operative confirmation. Adrenalectomy resulted in normal blood pressure in 59%, improvement in 25%, and no change in 16%. Correct localization of the lesion was obtained in 47% by the adrenal isotopic scan, in 66% by adrenal venography, and in 91% by the modified adrenal venous hormone technique despite four false-positives. Of the 26 patients with an anomalous postural decrease in plasma aldosterone, 88% had a unilateral lesion.", "contents": "Primary aldosteronism: diagnosis, localization, and treatment. New diagnostic techniques have enhanced the detection of primary aldosteronism. However, the response of blood pressure after operation in unilateral and bilateral adrenal disease is different. We have compared four localizing techniques--adrenal venography, adrenal isotopic scanning, a modified adrenal venous sampling for steroid measurements, and the anomalous postural decrease in plasma aldosterone concentration--in 51 patients with primary aldosteronism, all of whom had undergone operative confirmation. Adrenalectomy resulted in normal blood pressure in 59%, improvement in 25%, and no change in 16%. Correct localization of the lesion was obtained in 47% by the adrenal isotopic scan, in 66% by adrenal venography, and in 91% by the modified adrenal venous hormone technique despite four false-positives. Of the 26 patients with an anomalous postural decrease in plasma aldosterone, 88% had a unilateral lesion."}
{"id": "PMID:218485", "title": "[Adenylate cyclase activation in KB cells infected by Senda\u00ef virus (author's transl)].", "content": "Adenylate cyclase activity is increased in KB cells infected by a little dose of Senda\u00ef virus. The apparent Km for ATP substrate is decreased from 0.7 to 0.4 mM and the activity regulation is changed. This activation may be related to interactions between virus and cell membrane where adenylate cyclase is located.", "contents": "[Adenylate cyclase activation in KB cells infected by Senda\u00ef virus (author's transl)]. Adenylate cyclase activity is increased in KB cells infected by a little dose of Senda\u00ef virus. The apparent Km for ATP substrate is decreased from 0.7 to 0.4 mM and the activity regulation is changed. This activation may be related to interactions between virus and cell membrane where adenylate cyclase is located."}
{"id": "PMID:218488", "title": "[Crosti's reticulosis. Report on three cases, one with ultrastructural study (author's transl)].", "content": "Crosti's reticulosis is defined as a peculiar form of well-circumscribed, slow developing lymphomas in adults, with a malignant histological picture. Three cases with typical dorsal localisation according to Crosti's first description are reported and the cardinal features of this type of tumour are recalled. One observation includes an ultrastructural study which confirms the malignant nature of histiocytes in this disease. Localisation in back seems not to be exclusive and a study of 32 cases of the literature about other localised cutaneous reticulum cell lymphomas show them similar to Crosti's reticulosis-which authorizes their classification, as was proposed by Thiers in a single group of slow developing circumscribed reticuloses.", "contents": "[Crosti's reticulosis. Report on three cases, one with ultrastructural study (author's transl)]. Crosti's reticulosis is defined as a peculiar form of well-circumscribed, slow developing lymphomas in adults, with a malignant histological picture. Three cases with typical dorsal localisation according to Crosti's first description are reported and the cardinal features of this type of tumour are recalled. One observation includes an ultrastructural study which confirms the malignant nature of histiocytes in this disease. Localisation in back seems not to be exclusive and a study of 32 cases of the literature about other localised cutaneous reticulum cell lymphomas show them similar to Crosti's reticulosis-which authorizes their classification, as was proposed by Thiers in a single group of slow developing circumscribed reticuloses."}
{"id": "PMID:218489", "title": "Carcinoma of Stensen's duct.", "content": "The authors present 2 cases of carcinoma primary in Stensen's duct, one a mucoepidermoid carcinoma and the other an adenoid cystic carcinoma. This is an unusual site for a primary carcinoma and these are apparently the thirteenth and fourteenth cases to be reported in the English literature. The authors review the diagnosis and treatment for primary carcinoma of Stensen's duct.", "contents": "Carcinoma of Stensen's duct. The authors present 2 cases of carcinoma primary in Stensen's duct, one a mucoepidermoid carcinoma and the other an adenoid cystic carcinoma. This is an unusual site for a primary carcinoma and these are apparently the thirteenth and fourteenth cases to be reported in the English literature. The authors review the diagnosis and treatment for primary carcinoma of Stensen's duct."}
{"id": "PMID:218490", "title": "The effect of vaccination on titres of antibody to rotavirus in colostrum and milk.", "content": "The continued presence of antibody to rotavirus in the gut of the neonatal ruminant has been shown to be important in protecting against clinical disease associated with rotavirus infections. This effect is dependant upon the amount of antibody included in the diet. Titres of antibody to rotavirus may be relatively high in ruminant mammary secretions immediately after parturition but decline rapidly over the course of the first day. The influence of vaccination on the titres of antibody, the concentrations of immunoglobulin and their respective of decline in the mammary secretion following parturition has been studied. Ewes vaccinated two to three weeks prior to mating with an inactivated preparation of lamb rotavirus produced colostrum and milk after the subsequent pregnancy which contained significantly higher titres of antibody to the virus than did the mammary secretions from non-vaccinates. The antibody activity appears to be associated with IgG and it is suggested that vaccination may be of value in the alleviation of neonatal diarrhoea associated with rotavirus infection in cattle and sheep.", "contents": "The effect of vaccination on titres of antibody to rotavirus in colostrum and milk. The continued presence of antibody to rotavirus in the gut of the neonatal ruminant has been shown to be important in protecting against clinical disease associated with rotavirus infections. This effect is dependant upon the amount of antibody included in the diet. Titres of antibody to rotavirus may be relatively high in ruminant mammary secretions immediately after parturition but decline rapidly over the course of the first day. The influence of vaccination on the titres of antibody, the concentrations of immunoglobulin and their respective of decline in the mammary secretion following parturition has been studied. Ewes vaccinated two to three weeks prior to mating with an inactivated preparation of lamb rotavirus produced colostrum and milk after the subsequent pregnancy which contained significantly higher titres of antibody to the virus than did the mammary secretions from non-vaccinates. The antibody activity appears to be associated with IgG and it is suggested that vaccination may be of value in the alleviation of neonatal diarrhoea associated with rotavirus infection in cattle and sheep."}
{"id": "PMID:218487", "title": "Benign pleomorphic adenoma of the larynx. A case report.", "content": "Minor salivary gland tumors of the larynx are relatively rare. Morphologically the majority of them are adenoid cystic carcinomas and the overwhelming location is the subglottic larynx. Benign pleomorphic adenomas are rare minor salivary gland tumors of the larynx which usually occur at the glottic and subglottic levels. We present only the sixth case of a supraglottic benign pleomorphic adenoma that we could find in the literature. A preoperative laryngogram localized the tumor to the supraglottic larynx and the intact mucosa suggested a specific differential diagnosis. The tumor was removed by a lateral pharyngotomy with retention of good laryngeal function. The relatively asymptomatic presentation of our case is a somewhat unusual finding which, however, was previously noted in similar case reports.", "contents": "Benign pleomorphic adenoma of the larynx. A case report. Minor salivary gland tumors of the larynx are relatively rare. Morphologically the majority of them are adenoid cystic carcinomas and the overwhelming location is the subglottic larynx. Benign pleomorphic adenomas are rare minor salivary gland tumors of the larynx which usually occur at the glottic and subglottic levels. We present only the sixth case of a supraglottic benign pleomorphic adenoma that we could find in the literature. A preoperative laryngogram localized the tumor to the supraglottic larynx and the intact mucosa suggested a specific differential diagnosis. The tumor was removed by a lateral pharyngotomy with retention of good laryngeal function. The relatively asymptomatic presentation of our case is a somewhat unusual finding which, however, was previously noted in similar case reports."}
{"id": "PMID:218492", "title": "The detection of rotavirus specific antibody in colostrum and milk by ELISA.", "content": "The blocking method of ELISA for the detection and titration of rotavirus-specific antibody in colostrum is described. The results obtained were positively correlated with those of a neutralizing antibody test. On one farm colostrum samples were obtained over a period of 18 months. No relationship was found between the titer of colostrum obtained shortly after calving, and the development of rotavirus-associated diarrhoea in calves. On a second farm only samples obtained during the calving season were tested. Within this restricted period high colostral antibody titers appeared to reduce the incidence of diarrhoea among calves and to delay the onset of rotavirus excretion in the faeces. These results are discussed in relation to the rapid decline in antibody content of colostrum after calving.", "contents": "The detection of rotavirus specific antibody in colostrum and milk by ELISA. The blocking method of ELISA for the detection and titration of rotavirus-specific antibody in colostrum is described. The results obtained were positively correlated with those of a neutralizing antibody test. On one farm colostrum samples were obtained over a period of 18 months. No relationship was found between the titer of colostrum obtained shortly after calving, and the development of rotavirus-associated diarrhoea in calves. On a second farm only samples obtained during the calving season were tested. Within this restricted period high colostral antibody titers appeared to reduce the incidence of diarrhoea among calves and to delay the onset of rotavirus excretion in the faeces. These results are discussed in relation to the rapid decline in antibody content of colostrum after calving."}
{"id": "PMID:218494", "title": "[Response to ACTH of human adrenocortical cells isolated from normal glands and from adrenocortical adenoma (author's transl)].", "content": "The low sensitivity of adrenocortical adenoma to ACTH, documented in vivo, and in vitro, results from decreased cAMP generation in response to ACTH while distal steps of biosynthesis of cortisol are even more active in these tumoral cells than in normal adrenocortical cells.", "contents": "[Response to ACTH of human adrenocortical cells isolated from normal glands and from adrenocortical adenoma (author's transl)]. The low sensitivity of adrenocortical adenoma to ACTH, documented in vivo, and in vitro, results from decreased cAMP generation in response to ACTH while distal steps of biosynthesis of cortisol are even more active in these tumoral cells than in normal adrenocortical cells."}
{"id": "PMID:218495", "title": "Inhibition of the evoked release of acetylcholine by the porphyrin precursor delta-aminolevulinic acid.", "content": "The effect of delta-aminolevulinic acid (ALA) on neuromuscular transmission were studied. High concentrations (0.6 to 18 mM) of ALA caused significant reductions in the amplitudes of curarized end-plate potentials (epps). Changing the ratio of calcium to magnesium in the bathing solution allowed the quantal content of the epps to be directly measured. Under these conditions, ALA reduced the quantal content of epps without affecting the depolarization produced by a single quantum of acetylcholine. It was concluded that ALA, in high concentrations, inhibits the release of acetylcholine evoked by a nerve impulse but is unlikely to be the cause of the neurological defects of acute porphyria.", "contents": "Inhibition of the evoked release of acetylcholine by the porphyrin precursor delta-aminolevulinic acid. The effect of delta-aminolevulinic acid (ALA) on neuromuscular transmission were studied. High concentrations (0.6 to 18 mM) of ALA caused significant reductions in the amplitudes of curarized end-plate potentials (epps). Changing the ratio of calcium to magnesium in the bathing solution allowed the quantal content of the epps to be directly measured. Under these conditions, ALA reduced the quantal content of epps without affecting the depolarization produced by a single quantum of acetylcholine. It was concluded that ALA, in high concentrations, inhibits the release of acetylcholine evoked by a nerve impulse but is unlikely to be the cause of the neurological defects of acute porphyria."}
{"id": "PMID:218496", "title": "Low trimethoprim susceptibility of anaerobic bacteria due to insensitive dihydrofolate reductases.", "content": "All the 28 Bacteroides fragilis strains investigated were susceptible to sulfamethoxazole (minimal inhibitory concentration < 16 mug/ml) and resistant to trimethoprim (TMP; minimal inhibitory concentration > 4 mug/ml). Synergism between sulfamethoxazole and TMP was present in all strains at a ratio of 1:1. The few clostridia investigated proved more resistant to both compounds. Dihydrofolate reductases from B. fragilis, C. perfringens, and some other anaerobic species were isolated. Inhibition profiles with six structurally different inhibitors revealed major differences in all enzymes. For 50% inhibition, the enzyme from B. fragilis and all clostridia required concentrations of TMP which were between several hundredfold and 1,000-fold higher than those required for the enzyme of Escherichia coli, whereas the enzyme from Propionibacterium acnes only needed a threefold higher concentration. In vitro activities of TMP were seen to correspond to the activity at the enzymatic level in B. fragilis and P. acnes, but correspond to a much lesser extent to the activity at the enzymatic level in clostridia, where a poor penetration is assumed to be involved. Dihydrofolate reductase inhibitors other than TMP were found to be as active as TMP both at the enzyme and in vitro. In B. fragilis, higher concentrations of exogenous thymidine were required for increasing the minimal inhibitory concentration of TMP than in E. coli and probably also in C. perfringens.", "contents": "Low trimethoprim susceptibility of anaerobic bacteria due to insensitive dihydrofolate reductases. All the 28 Bacteroides fragilis strains investigated were susceptible to sulfamethoxazole (minimal inhibitory concentration < 16 mug/ml) and resistant to trimethoprim (TMP; minimal inhibitory concentration > 4 mug/ml). Synergism between sulfamethoxazole and TMP was present in all strains at a ratio of 1:1. The few clostridia investigated proved more resistant to both compounds. Dihydrofolate reductases from B. fragilis, C. perfringens, and some other anaerobic species were isolated. Inhibition profiles with six structurally different inhibitors revealed major differences in all enzymes. For 50% inhibition, the enzyme from B. fragilis and all clostridia required concentrations of TMP which were between several hundredfold and 1,000-fold higher than those required for the enzyme of Escherichia coli, whereas the enzyme from Propionibacterium acnes only needed a threefold higher concentration. In vitro activities of TMP were seen to correspond to the activity at the enzymatic level in B. fragilis and P. acnes, but correspond to a much lesser extent to the activity at the enzymatic level in clostridia, where a poor penetration is assumed to be involved. Dihydrofolate reductase inhibitors other than TMP were found to be as active as TMP both at the enzyme and in vitro. In B. fragilis, higher concentrations of exogenous thymidine were required for increasing the minimal inhibitory concentration of TMP than in E. coli and probably also in C. perfringens."}
{"id": "PMID:218497", "title": "Effects of nucleoside analogs on Epstein-Barr virus-induced transformation of human umbilical cord leukocytes and Epstein-Barr virus expression in transformed cells.", "content": "Two methods of assay, measuring (i) stimulation of host cell DNA synthesis by [(3)H]thymidine incorporation and (ii) morphological transformation in microtiter plates, were employed to determine what effect treatment during infection with adenine arabinoside or 5-iodo-5'-amino-2',5'-dideoxyuridine has on Epstein-Barr virus (EBV) (B95-8)-induced transformation of human umbilical cord leukocytes. It was found that adenine arabinoside inhibited EBV-induced transformation in a dose-dependent manner in both assays, beginning at drug concentrations (<2 mug/ml) which had little effect on either spontaneous or phytohemagglutinin-induced host cell DNA synthesis. Adenine arabinoside was more effective in inhibiting morphological transformation than EBV-induced host DNA synthesis. Adenine arabinoside treatment was also effective in reducing both EB viral capsid antigen expression and production of biologically active extracellular transforming virus in EBV-transformed cells. In contrast, 5-iodo-5'-amino-2',5'-dideoxyuridine, which inhibited herpes simplex virus replication, had little effect on EBV-induced transformation as measured by either method of assay. However, 5-iodo-5'-amino-2',5'-dideoxyuridine was found to be effective in inhibiting viral capsid antigen expression and production of extracellular transforming virus in EBV-transformed cells.", "contents": "Effects of nucleoside analogs on Epstein-Barr virus-induced transformation of human umbilical cord leukocytes and Epstein-Barr virus expression in transformed cells. Two methods of assay, measuring (i) stimulation of host cell DNA synthesis by [(3)H]thymidine incorporation and (ii) morphological transformation in microtiter plates, were employed to determine what effect treatment during infection with adenine arabinoside or 5-iodo-5'-amino-2',5'-dideoxyuridine has on Epstein-Barr virus (EBV) (B95-8)-induced transformation of human umbilical cord leukocytes. It was found that adenine arabinoside inhibited EBV-induced transformation in a dose-dependent manner in both assays, beginning at drug concentrations (<2 mug/ml) which had little effect on either spontaneous or phytohemagglutinin-induced host cell DNA synthesis. Adenine arabinoside was more effective in inhibiting morphological transformation than EBV-induced host DNA synthesis. Adenine arabinoside treatment was also effective in reducing both EB viral capsid antigen expression and production of biologically active extracellular transforming virus in EBV-transformed cells. In contrast, 5-iodo-5'-amino-2',5'-dideoxyuridine, which inhibited herpes simplex virus replication, had little effect on EBV-induced transformation as measured by either method of assay. However, 5-iodo-5'-amino-2',5'-dideoxyuridine was found to be effective in inhibiting viral capsid antigen expression and production of extracellular transforming virus in EBV-transformed cells."}
{"id": "PMID:218498", "title": "Enveloped virus inactivation by fatty acid derivatives.", "content": "The enveloped bacteriophage phi6 has been shown to be a valuable model system for the preliminary screening of compounds that might be expected to inactivate herpes simplex virus and other enveloped mammalian viruses. A variety of fatty acid derivatives that form fluid micelles in aqueous media have been found to be potent inactivators of phi6. The chemical nature of the polar head group, the length of the alkyl chain(s), and the extent and geometry of unsaturation are all important parameters in determining the antiviral effectiveness of this class of compounds.", "contents": "Enveloped virus inactivation by fatty acid derivatives. The enveloped bacteriophage phi6 has been shown to be a valuable model system for the preliminary screening of compounds that might be expected to inactivate herpes simplex virus and other enveloped mammalian viruses. A variety of fatty acid derivatives that form fluid micelles in aqueous media have been found to be potent inactivators of phi6. The chemical nature of the polar head group, the length of the alkyl chain(s), and the extent and geometry of unsaturation are all important parameters in determining the antiviral effectiveness of this class of compounds."}
{"id": "PMID:218499", "title": "Extreme sensitivity of enveloped viruses, including herpes simplex, to long-chain unsaturated monoglycerides and alcohols.", "content": "Unsaturated monoglycerides and alcohols of chain lengths of 16 or 18 carbons were found to be extremely potent inactivators of two enveloped viruses, herpes simplex virus type 2 and bacteriophage phi6. The lipid-containing bacteriophage PM2 was also inactivated by some of these amphiphilic molecules. Treatment of herpes simplex virus type 2 with these compounds at concentrations as low as 0.2 muM reduced virus survival to 50% in 30 min, making these agents the most potent inactivators of herpes simplex viruses discovered that are not cytotoxic to mammalian cells. Detailed characterizations of the effects of unsaturated monoglycerides and alcohols on bacteriophages phi6 and PM2 showed that the inactivated phi6 virion remained nearly intact but that PM2 was almost completely disrupted by the inactivating treatment. Some of the compounds inactivate the viruses even at low temperature (0 degrees C). Excess amounts of diglycerides and phospholipids interfere with the inactivating abilities of some of the unsaturated monoglycerides and alcohols against phi6 and PM2. Our findings suggest that the unsaturated monoglycerides and some of the unsaturated alcohols should be further studied as potential antiviral agents, particularly for application to herpesvirus-infected areas of the skin and accessible epithelium.", "contents": "Extreme sensitivity of enveloped viruses, including herpes simplex, to long-chain unsaturated monoglycerides and alcohols. Unsaturated monoglycerides and alcohols of chain lengths of 16 or 18 carbons were found to be extremely potent inactivators of two enveloped viruses, herpes simplex virus type 2 and bacteriophage phi6. The lipid-containing bacteriophage PM2 was also inactivated by some of these amphiphilic molecules. Treatment of herpes simplex virus type 2 with these compounds at concentrations as low as 0.2 muM reduced virus survival to 50% in 30 min, making these agents the most potent inactivators of herpes simplex viruses discovered that are not cytotoxic to mammalian cells. Detailed characterizations of the effects of unsaturated monoglycerides and alcohols on bacteriophages phi6 and PM2 showed that the inactivated phi6 virion remained nearly intact but that PM2 was almost completely disrupted by the inactivating treatment. Some of the compounds inactivate the viruses even at low temperature (0 degrees C). Excess amounts of diglycerides and phospholipids interfere with the inactivating abilities of some of the unsaturated monoglycerides and alcohols against phi6 and PM2. Our findings suggest that the unsaturated monoglycerides and some of the unsaturated alcohols should be further studied as potential antiviral agents, particularly for application to herpesvirus-infected areas of the skin and accessible epithelium."}
{"id": "PMID:218500", "title": "Mechanism of aminoglycoside antibiotic resistance in anaerobic bacteria: Clostridium perfringens and Bacteroides fragilis.", "content": "Cell-free amino acid incorporation using ribosomes from strains of either Clostridium perfringens or Bacteroides fragilis was shown to be susceptible to inhibition by streptomycin and gentamicin. Ribosomes bound dihydrostreptomycin as effectively as ribosomes from Escherichia coli. No inactivation of streptomycin or gentamicin was detected by cell extracts of either anaerobic bacterial species. B. fragilis, grown without added hemin, menadione, and fumarate, and C. perfringens did not show any time-dependent accumulation of dihydrostreptomycin or gentamicin at concentrations tested. Decreased resistance to aminoglycosides and time-dependent uptake of dihydrostreptomycin at 500 mug/ml was observed with B. fragilis grown with hemin, menadione, and fumarate. With the last additions, cytochrome b was detected by cytochrome spectra of B. fragilis. These results demonstrate that anaerobic bacteria unable to carry out oxygen- or nitrate-dependent electron transport are resistant to streptomycin and gentamicin because of failure to transport aminoglycosides. The induction of fumarate-dependent electron transport in B. fragilis is associated with some aminoglycoside transport that is of poor efficiency relative to bacteria with electron transport to oxygen or nitrate.", "contents": "Mechanism of aminoglycoside antibiotic resistance in anaerobic bacteria: Clostridium perfringens and Bacteroides fragilis. Cell-free amino acid incorporation using ribosomes from strains of either Clostridium perfringens or Bacteroides fragilis was shown to be susceptible to inhibition by streptomycin and gentamicin. Ribosomes bound dihydrostreptomycin as effectively as ribosomes from Escherichia coli. No inactivation of streptomycin or gentamicin was detected by cell extracts of either anaerobic bacterial species. B. fragilis, grown without added hemin, menadione, and fumarate, and C. perfringens did not show any time-dependent accumulation of dihydrostreptomycin or gentamicin at concentrations tested. Decreased resistance to aminoglycosides and time-dependent uptake of dihydrostreptomycin at 500 mug/ml was observed with B. fragilis grown with hemin, menadione, and fumarate. With the last additions, cytochrome b was detected by cytochrome spectra of B. fragilis. These results demonstrate that anaerobic bacteria unable to carry out oxygen- or nitrate-dependent electron transport are resistant to streptomycin and gentamicin because of failure to transport aminoglycosides. The induction of fumarate-dependent electron transport in B. fragilis is associated with some aminoglycoside transport that is of poor efficiency relative to bacteria with electron transport to oxygen or nitrate."}
{"id": "PMID:218501", "title": "Influence of suspending media upon the susceptibility of Pseudomonas aeruginosa NCTC 6750 and its spheroplasts to polymyxin B.", "content": "The lytic and bactericidal actions of polymyxin B on whole cells and spheroplasts of Pseudomonas aeruginosa varied markedly with the suspending media, and there was little correlation between them. Relative rates of lysis of these preparations and also of Bacillus megaterium protoplasts suggested that polymyxin causes progressive damage to the cytoplasmic membrane, such that membrane permeability towards various ions increased as follows: K(+) > Na(+) > NO(3) (-) > Cl(-), Ca(2+), H(2)PO(4) (-)/HPO(4) (2-). Impermeant compounds, such as NaCl and sucrose, protected whole cells against lysis but not against death. It is suggested that lysis of whole cells by polymyxin is a secondary effect, resulting from entry of solutes normally excluded by the cytoplasmic membrane and the fragility of the damaged outer membrane. Because the degree of lysis varies with the external solutes, it should be treated with caution as a descriptor of polymyxin activity.", "contents": "Influence of suspending media upon the susceptibility of Pseudomonas aeruginosa NCTC 6750 and its spheroplasts to polymyxin B. The lytic and bactericidal actions of polymyxin B on whole cells and spheroplasts of Pseudomonas aeruginosa varied markedly with the suspending media, and there was little correlation between them. Relative rates of lysis of these preparations and also of Bacillus megaterium protoplasts suggested that polymyxin causes progressive damage to the cytoplasmic membrane, such that membrane permeability towards various ions increased as follows: K(+) > Na(+) > NO(3) (-) > Cl(-), Ca(2+), H(2)PO(4) (-)/HPO(4) (2-). Impermeant compounds, such as NaCl and sucrose, protected whole cells against lysis but not against death. It is suggested that lysis of whole cells by polymyxin is a secondary effect, resulting from entry of solutes normally excluded by the cytoplasmic membrane and the fragility of the damaged outer membrane. Because the degree of lysis varies with the external solutes, it should be treated with caution as a descriptor of polymyxin activity."}
{"id": "PMID:218505", "title": "Spread to the nipple and areola in carcinoma of the breast.", "content": "In 40 breasts with primary carcinoma, the nipple and areola were cut horizontally in order to investigate the frequency of intraductal and invasive cancer. In 20 of these breasts the nipple and/or areola were found to be involved at a depth of 1 cm (50%; 95% confidence limits: 33.8-66.2%). Eleven neoplasms were purely intraductal, eight intraductal as well as stromal, and only one purely stromal. By means of clinical or physical findings, it was not possible to select the breasts in which the nipple and/or areola were not involved. It is concluded that the general use of surgical methods preserving the nipple and areola in treating breast cancer leaves a focus of invasive or intraductal carcinoma in about half the patients. The implications of this are not known.", "contents": "Spread to the nipple and areola in carcinoma of the breast. In 40 breasts with primary carcinoma, the nipple and areola were cut horizontally in order to investigate the frequency of intraductal and invasive cancer. In 20 of these breasts the nipple and/or areola were found to be involved at a depth of 1 cm (50%; 95% confidence limits: 33.8-66.2%). Eleven neoplasms were purely intraductal, eight intraductal as well as stromal, and only one purely stromal. By means of clinical or physical findings, it was not possible to select the breasts in which the nipple and/or areola were not involved. It is concluded that the general use of surgical methods preserving the nipple and areola in treating breast cancer leaves a focus of invasive or intraductal carcinoma in about half the patients. The implications of this are not known."}
{"id": "PMID:218506", "title": "Noninvasive breast carcinoma: frequency of unsuspected invasion and implications for treatment.", "content": "One hundred twenty-nine biopsies from 121 patients with a frozen or paraffin section diagnosis of noninvasive breast carcinoma were studied. Eight women had bilateral noninvasive carcinoma. Seven biopsies reported as intraductal on frozen section contained invasive carcinoma on paraffin section. Of the remaining 122 biopsies proven to have noninvasive carcinoma on paraffin section, 39 (34%) were reported at frozen section and as noninvasive carcinoma, 24 (20%) as atypical and 59 (48%) as benign. Intraductal carcinoma (IDC) was identified more often at frozen section (45%) than was lobular carcinoma in situ (19%). Among 41 patients who had bilateral carcinoma with invasive disease in one breast, 76% of contralateral noninvasive carcinoma was LCIS. After excisional biopsy, carcinoma was found in 56% of 103 mastectomy specimens, including invasive carcinoma in 6% of breasts with IDC and 4% with LCIS. Residual noninvasive carcinoma was usually of the same type found at biopsy (90% IDC and 88% LCIS) and involved quadrants other than the biopsy site in 33% with IDC and in 80% with LCIS. When the frozen or paraffin section diagnosis of a generous excisional biopsy was noninvasive breast carcinoma, there was a substantial risk that foci of the same type of noninvasive carcinoma were also present in other quadrants. However, occult foci of invasive carcinoma were quite infrequent and the risk of axillary metastases was very low. Adequate treatment for noninvasive carcinoma requires elimination of all residual foci of noninvasive disease. At present this can best be accomplished by total mastectomy if the operation is properly performed. To insure removal of the axillary extension of the breast and for staging, in continuity dissection of the lowest axillary lymph nodes is also prudent.", "contents": "Noninvasive breast carcinoma: frequency of unsuspected invasion and implications for treatment. One hundred twenty-nine biopsies from 121 patients with a frozen or paraffin section diagnosis of noninvasive breast carcinoma were studied. Eight women had bilateral noninvasive carcinoma. Seven biopsies reported as intraductal on frozen section contained invasive carcinoma on paraffin section. Of the remaining 122 biopsies proven to have noninvasive carcinoma on paraffin section, 39 (34%) were reported at frozen section and as noninvasive carcinoma, 24 (20%) as atypical and 59 (48%) as benign. Intraductal carcinoma (IDC) was identified more often at frozen section (45%) than was lobular carcinoma in situ (19%). Among 41 patients who had bilateral carcinoma with invasive disease in one breast, 76% of contralateral noninvasive carcinoma was LCIS. After excisional biopsy, carcinoma was found in 56% of 103 mastectomy specimens, including invasive carcinoma in 6% of breasts with IDC and 4% with LCIS. Residual noninvasive carcinoma was usually of the same type found at biopsy (90% IDC and 88% LCIS) and involved quadrants other than the biopsy site in 33% with IDC and in 80% with LCIS. When the frozen or paraffin section diagnosis of a generous excisional biopsy was noninvasive breast carcinoma, there was a substantial risk that foci of the same type of noninvasive carcinoma were also present in other quadrants. However, occult foci of invasive carcinoma were quite infrequent and the risk of axillary metastases was very low. Adequate treatment for noninvasive carcinoma requires elimination of all residual foci of noninvasive disease. At present this can best be accomplished by total mastectomy if the operation is properly performed. To insure removal of the axillary extension of the breast and for staging, in continuity dissection of the lowest axillary lymph nodes is also prudent."}
{"id": "PMID:218507", "title": "[First Madagascan myxovirus B isolated during an influenza epidemic in Antananarivo (June-August 1977)].", "content": "The authors study an influenza epidemic at Antananarivo, during the austral winter 1977. A virologic work confirmed the diagnostic of influenza with the isolation of two influenza B virus strains. An epidemiologic survey was also carried out in consultant people at the Work Medecine Department and Hygiene Municipal Service to evaluate its influency on morbidity and mortality.", "contents": "[First Madagascan myxovirus B isolated during an influenza epidemic in Antananarivo (June-August 1977)]. The authors study an influenza epidemic at Antananarivo, during the austral winter 1977. A virologic work confirmed the diagnostic of influenza with the isolation of two influenza B virus strains. An epidemiologic survey was also carried out in consultant people at the Work Medecine Department and Hygiene Municipal Service to evaluate its influency on morbidity and mortality."}
{"id": "PMID:218508", "title": "Facilitatory effect of naloxone and involvement of specific ligand-opiate receptor system in the antinociceptive effects of non-opioid drugs.", "content": "The facilitatory effects exerted by naloxone on a nociceptive reaction (jumping) in the hot plate test was not modified by three phosphodiesterase inhibitors, theophylline, Ro-20-1724 and I.C.I. 63197 which had on themselves different effects on the latency of jumping. The facilitatory effects of naloxone were not diminished by neuroleptics, cholinergic agonists or miscellaneous drugs (baclofen, indomethacin, ketoprofen, n-dipropylacetate, diazepam and potassium chlorazepate). Naloxone antagonized the antinocieceptive effects of neuroleptics in different patterns. No competitive component could be observed with haloperidol, whereas such a phenomenon was apparent with benperidol. Pimozide was an intermediary case. The antinociceptive effects of two cholinergic agonists, arecoline and eserine were antagonized by naloxone and stereospecifically by the (-) isomer, Mr 2266. The (+) isomer, Mr 2267 was inactive. The antagonism by the opioid antagonists of the antinociceptive effects of cholinergic agonists appeared to be of a competitive type. Thus the facilitatory effects of naloxone did not apparently involve activation of adenyl cyclase or the mediation of dopaminergic or cholinergic (neural) structures. The antinociceptive effects of benperidol and pimozide but not of haloperidol might result from the triggering of specific opiate receptors and those of cholinergic agonists from such a triggering and/or from release of endogenous ligands.", "contents": "Facilitatory effect of naloxone and involvement of specific ligand-opiate receptor system in the antinociceptive effects of non-opioid drugs. The facilitatory effects exerted by naloxone on a nociceptive reaction (jumping) in the hot plate test was not modified by three phosphodiesterase inhibitors, theophylline, Ro-20-1724 and I.C.I. 63197 which had on themselves different effects on the latency of jumping. The facilitatory effects of naloxone were not diminished by neuroleptics, cholinergic agonists or miscellaneous drugs (baclofen, indomethacin, ketoprofen, n-dipropylacetate, diazepam and potassium chlorazepate). Naloxone antagonized the antinocieceptive effects of neuroleptics in different patterns. No competitive component could be observed with haloperidol, whereas such a phenomenon was apparent with benperidol. Pimozide was an intermediary case. The antinociceptive effects of two cholinergic agonists, arecoline and eserine were antagonized by naloxone and stereospecifically by the (-) isomer, Mr 2266. The (+) isomer, Mr 2267 was inactive. The antagonism by the opioid antagonists of the antinociceptive effects of cholinergic agonists appeared to be of a competitive type. Thus the facilitatory effects of naloxone did not apparently involve activation of adenyl cyclase or the mediation of dopaminergic or cholinergic (neural) structures. The antinociceptive effects of benperidol and pimozide but not of haloperidol might result from the triggering of specific opiate receptors and those of cholinergic agonists from such a triggering and/or from release of endogenous ligands."}
{"id": "PMID:218509", "title": "Effects of cyclic AMP and of protein kinase on the calcium uptake by various tracheal smooth muscle organelles.", "content": "The role of cyclic AMP, if any, in the regulation of smooth muscle tone is not understood. In the present study the effects of cyclic AMP and of protein kinase on the uptake of calcium by \"microsomal\", \"plasma\" and \"mitochondrial\" preparations obtained from bovine tracheal smooth muscle were examined. Cyclic AMP and protein kinase had only a slight and variable effect on the uptake of calcium by microsomes, and no effect on the uptake of calcium by the plasma membrane or the mitochondria. These findings are not compatible with a role of cyclic AMP and protein kinase in the control of the uptake of calcium by the subcellular organelles of tracheal smooth muscle.", "contents": "Effects of cyclic AMP and of protein kinase on the calcium uptake by various tracheal smooth muscle organelles. The role of cyclic AMP, if any, in the regulation of smooth muscle tone is not understood. In the present study the effects of cyclic AMP and of protein kinase on the uptake of calcium by \"microsomal\", \"plasma\" and \"mitochondrial\" preparations obtained from bovine tracheal smooth muscle were examined. Cyclic AMP and protein kinase had only a slight and variable effect on the uptake of calcium by microsomes, and no effect on the uptake of calcium by the plasma membrane or the mitochondria. These findings are not compatible with a role of cyclic AMP and protein kinase in the control of the uptake of calcium by the subcellular organelles of tracheal smooth muscle."}
{"id": "PMID:218512", "title": "Pulmonary cytomegalovirus infection: detection by Gallium 67 imaging in the transplant patient.", "content": "Cytomegalovirus (CMV) infeciton is a frequent complication during the first few months following renal transplantation. The diagnosis is sometimes difficult but may be made by viral culture, a fourfold rise in the CMV antibody titer, or by demonstration of the CMV inclusions in the affected tissue. An increased pulmonary uptake of galliulm citrate Ga 67 has been demonstrated following renal transplantation in two patients, each of whom had a fourfold rise in CMV complement fixing antibody titer, one of whom additionally had CMV inclusion bodies in a lung biopsy specimen prior to clinical or radiological demonstration of the pulmonary involvement. Gallium imaging, therefore, appears to be a valuable noninvasive test for early diagnosis of CMV pulmonary infections.", "contents": "Pulmonary cytomegalovirus infection: detection by Gallium 67 imaging in the transplant patient. Cytomegalovirus (CMV) infeciton is a frequent complication during the first few months following renal transplantation. The diagnosis is sometimes difficult but may be made by viral culture, a fourfold rise in the CMV antibody titer, or by demonstration of the CMV inclusions in the affected tissue. An increased pulmonary uptake of galliulm citrate Ga 67 has been demonstrated following renal transplantation in two patients, each of whom had a fourfold rise in CMV complement fixing antibody titer, one of whom additionally had CMV inclusion bodies in a lung biopsy specimen prior to clinical or radiological demonstration of the pulmonary involvement. Gallium imaging, therefore, appears to be a valuable noninvasive test for early diagnosis of CMV pulmonary infections."}
{"id": "PMID:218513", "title": "Viral pericarditis in patients receiving hemodialysis.", "content": "Four patients with end-stage renal disease in whom pericarditis developed while they received intermittent hemodialysis therapy were evaluated for viral infection. We found high or rising serum antibody titers to influenza virus A (three patients) and coxsackievirus B (one patient). Cardiac tamponade occurred in three patients, requiring pericardiectomy in two; each patient eventually recovered. Viral pericarditis may be an important cause of \"uremic\" pericarditis in chronically dialyzed patients.", "contents": "Viral pericarditis in patients receiving hemodialysis. Four patients with end-stage renal disease in whom pericarditis developed while they received intermittent hemodialysis therapy were evaluated for viral infection. We found high or rising serum antibody titers to influenza virus A (three patients) and coxsackievirus B (one patient). Cardiac tamponade occurred in three patients, requiring pericardiectomy in two; each patient eventually recovered. Viral pericarditis may be an important cause of \"uremic\" pericarditis in chronically dialyzed patients."}
{"id": "PMID:218514", "title": "Inappropriate antidiuretic hormone complicating histiocytic lymphoma.", "content": "The syndrome of inappropriate antidiuretic hormone (IADH) often causes the hyponatremia that may be seen in patients with malignant disorders. Most physicians correctly associate IADH with small cell carcinoma of the lung. We describe two patients in whom IADH was caused by histiocytic lymphoma. One patient was thought to have small cell carcinoma of the lung on the basis of marrow infiltration and the IADH. When the proper diagnosis was made and therapy instituted, both patients responded, with rapid resolution of their disease and the IADH. The identification of the neoplasm that produces the IADH is important, since histiocytic lymphoma may mimic small cell carcinoma of the lung, yet may be very responsive with newer treatment regimens.", "contents": "Inappropriate antidiuretic hormone complicating histiocytic lymphoma. The syndrome of inappropriate antidiuretic hormone (IADH) often causes the hyponatremia that may be seen in patients with malignant disorders. Most physicians correctly associate IADH with small cell carcinoma of the lung. We describe two patients in whom IADH was caused by histiocytic lymphoma. One patient was thought to have small cell carcinoma of the lung on the basis of marrow infiltration and the IADH. When the proper diagnosis was made and therapy instituted, both patients responded, with rapid resolution of their disease and the IADH. The identification of the neoplasm that produces the IADH is important, since histiocytic lymphoma may mimic small cell carcinoma of the lung, yet may be very responsive with newer treatment regimens."}
{"id": "PMID:218515", "title": "Metabolism of cyclic AMP in non-pathogenic Mycobacterium smegmatis.", "content": "The intracellular concentration of cyclic AMP reached a maximum in 3.5-day old cultures of Mycobacterium smegmatis grown in the presence of glycerol as the main source of carbon. Glucose-grown cells exhibited decreased cyclic AMP levels at all stages of growth. When M. smegmatis cells were incubated with various metabolites, pyruvate increased whereas glucose, ctric acid, succinic acid and lactic acid decreased intracellular cyclic AMP levels. No cyclic AMP was detected in the incubation medium. The presence of a cyclic AMP-binding protein was demonstrated in cell-free extracts of M. smegmatis.", "contents": "Metabolism of cyclic AMP in non-pathogenic Mycobacterium smegmatis. The intracellular concentration of cyclic AMP reached a maximum in 3.5-day old cultures of Mycobacterium smegmatis grown in the presence of glycerol as the main source of carbon. Glucose-grown cells exhibited decreased cyclic AMP levels at all stages of growth. When M. smegmatis cells were incubated with various metabolites, pyruvate increased whereas glucose, ctric acid, succinic acid and lactic acid decreased intracellular cyclic AMP levels. No cyclic AMP was detected in the incubation medium. The presence of a cyclic AMP-binding protein was demonstrated in cell-free extracts of M. smegmatis."}
{"id": "PMID:218516", "title": "[Hypertrophic and exudative gastropathy in the child].", "content": "A case of transient hypertrophic and exsudative gastritis, diagnosed in a 4 year-old female is reported. In the light of the recent data published, the authors comment on the particularities of the disease in childhood. The disparity of symptoms, the frequency of mild anaemia and of eosinophilia, a past history of allergy or a concomittant viral infection, the diffuse anatomic changes without polyps and lastly, a transient course of the disease with spontaneous recovery are the most striking features which characterize this entity in childhood.", "contents": "[Hypertrophic and exudative gastropathy in the child]. A case of transient hypertrophic and exsudative gastritis, diagnosed in a 4 year-old female is reported. In the light of the recent data published, the authors comment on the particularities of the disease in childhood. The disparity of symptoms, the frequency of mild anaemia and of eosinophilia, a past history of allergy or a concomittant viral infection, the diffuse anatomic changes without polyps and lastly, a transient course of the disease with spontaneous recovery are the most striking features which characterize this entity in childhood."}
{"id": "PMID:218518", "title": "Pulmonary alveolar proteinosis and cytomegalovirus infection.", "content": "We report a case of pulmonary alveolar proteinosis (PAP) and cytomegalovirus (CMV) infection occurring in a 5-year-old boy with acute lymphoblastic leukemia. The association of PAP and CMV infection is rare, but the possible etiologic role of CMV in the production of PAP is raised. Pulmonary alveolar proteinosis is being reported with increasing frequency in immunocompromised patients, and this disease may be difficult to distinguish from other causes of diffuse lung disease both clinically and radiologically. Pulmonary alveolar proteinosis, either alone or in combination with CMV infection, should therefore be considered in the differential diagnosis of diffuse lung disease in these cases.", "contents": "Pulmonary alveolar proteinosis and cytomegalovirus infection. We report a case of pulmonary alveolar proteinosis (PAP) and cytomegalovirus (CMV) infection occurring in a 5-year-old boy with acute lymphoblastic leukemia. The association of PAP and CMV infection is rare, but the possible etiologic role of CMV in the production of PAP is raised. Pulmonary alveolar proteinosis is being reported with increasing frequency in immunocompromised patients, and this disease may be difficult to distinguish from other causes of diffuse lung disease both clinically and radiologically. Pulmonary alveolar proteinosis, either alone or in combination with CMV infection, should therefore be considered in the differential diagnosis of diffuse lung disease in these cases."}
{"id": "PMID:218519", "title": "Goblet cell carcinoid tumor of the appendix. Report of five cases and review of the literature.", "content": "Five cases of goblet cell carcinoid tumor of the appendix showed characteristic histologic features that justified classification of these lesions as mucinous variants of carcinoid tumor. The tumor has low-grade malignancy, and metastases are uncommon. Resemblance to mucinous adenocarcinoma of the appendix is striking, and the features that help to differentiate the two lesions are delineated.", "contents": "Goblet cell carcinoid tumor of the appendix. Report of five cases and review of the literature. Five cases of goblet cell carcinoid tumor of the appendix showed characteristic histologic features that justified classification of these lesions as mucinous variants of carcinoid tumor. The tumor has low-grade malignancy, and metastases are uncommon. Resemblance to mucinous adenocarcinoma of the appendix is striking, and the features that help to differentiate the two lesions are delineated."}
{"id": "PMID:218520", "title": "Diffuse metanephric adenoma after in utero aspirin intoxication. A unique case of progressive renal failure.", "content": "Diffuse persistent glomerular immaturity and focal proximal tubular ectasia were seen in bilateral open renal biopsy specimens for an infant with fluid and salt depletion and slowly progressive renal failure. Subsequently, diffuse tubulopapillary renal adenoma subtotally replaced each kidney, thereby, necessitating renal transplantation. Origin of diffuse metanephric adenoma from persistent primitive epithelium of the proximal nephron is postulated and partly substantiated. We propose that this case of persistent proximal nephronic epithelial immaturity and diffuse metanephric adenoma is a variant of nephroblastomatosis and that in this case, a first trimester suicide attempt with aspirin may have initiated the maturation defect that preceded neoplastic transformation.", "contents": "Diffuse metanephric adenoma after in utero aspirin intoxication. A unique case of progressive renal failure. Diffuse persistent glomerular immaturity and focal proximal tubular ectasia were seen in bilateral open renal biopsy specimens for an infant with fluid and salt depletion and slowly progressive renal failure. Subsequently, diffuse tubulopapillary renal adenoma subtotally replaced each kidney, thereby, necessitating renal transplantation. Origin of diffuse metanephric adenoma from persistent primitive epithelium of the proximal nephron is postulated and partly substantiated. We propose that this case of persistent proximal nephronic epithelial immaturity and diffuse metanephric adenoma is a variant of nephroblastomatosis and that in this case, a first trimester suicide attempt with aspirin may have initiated the maturation defect that preceded neoplastic transformation."}
{"id": "PMID:218521", "title": "Male breast carcinoma. An ultrastructural study.", "content": "A case of infiltrating ductal carcinoma of the male breast was studied by electron microscopy. The ultrastructure of the tumor is similar to that described in the female breast. Myofibroblasts are the preponderant cells in the stroma. Their significance and possible relation to hormonal stimuli are discussed.", "contents": "Male breast carcinoma. An ultrastructural study. A case of infiltrating ductal carcinoma of the male breast was studied by electron microscopy. The ultrastructure of the tumor is similar to that described in the female breast. Myofibroblasts are the preponderant cells in the stroma. Their significance and possible relation to hormonal stimuli are discussed."}
{"id": "PMID:218522", "title": "Low-grade mucoepidermoid carcinoma of the breast.", "content": "Two cases of primary breast carcinoma morphologically identical to low-grade mucoepidermoid carcinoma of salivary gland origin occurred. To our knowledge, this article represents the first description of this tumor type in the breast. Both lesions were well circumscribed, wholly or partially cystic, and composed of intimately associated, well-differentiated, squamous and mucinous glandular epithelium. It is suggested that these may represent an indolent tumor type in the breast analogous to their behavior in the salivary gland.", "contents": "Low-grade mucoepidermoid carcinoma of the breast. Two cases of primary breast carcinoma morphologically identical to low-grade mucoepidermoid carcinoma of salivary gland origin occurred. To our knowledge, this article represents the first description of this tumor type in the breast. Both lesions were well circumscribed, wholly or partially cystic, and composed of intimately associated, well-differentiated, squamous and mucinous glandular epithelium. It is suggested that these may represent an indolent tumor type in the breast analogous to their behavior in the salivary gland."}
{"id": "PMID:218526", "title": "Percutaneous decompression of benign and malignant biliary obstruction.", "content": "Percutaneous transhepatic catheterization of the biliary tree was performed in 41 patients with obstructive jaundice. In 39 patients, the catheter was successfully advanced past the obstructing lesion into the distal common duct and duodenum to establish internal biliary drainage. The remaining two patients had the obstructed biliary tract drained externally. Chronic internal catheter drainage was instituted in five patients with stricture and ten with malignant obstruction as a means of palliating symptomatic jaundice. Twenty-two patients had marked reduction in serum bilirubin levels and pruritus, eight patients had moderate decreases in serum bilirubin levels, and six patients did not improve despite adequate catheterization due to hepatic parenchymal disease. This procedure effectively decompresses the severely obstructed biliary tree prior to surgery and can also palliate patients with unresectable malignant biliary obstruction and stent high-risk, benign strictures.", "contents": "Percutaneous decompression of benign and malignant biliary obstruction. Percutaneous transhepatic catheterization of the biliary tree was performed in 41 patients with obstructive jaundice. In 39 patients, the catheter was successfully advanced past the obstructing lesion into the distal common duct and duodenum to establish internal biliary drainage. The remaining two patients had the obstructed biliary tract drained externally. Chronic internal catheter drainage was instituted in five patients with stricture and ten with malignant obstruction as a means of palliating symptomatic jaundice. Twenty-two patients had marked reduction in serum bilirubin levels and pruritus, eight patients had moderate decreases in serum bilirubin levels, and six patients did not improve despite adequate catheterization due to hepatic parenchymal disease. This procedure effectively decompresses the severely obstructed biliary tree prior to surgery and can also palliate patients with unresectable malignant biliary obstruction and stent high-risk, benign strictures."}
{"id": "PMID:218524", "title": "Research on cholesterol, steroidal hormones and liposoluble vitamins by thin layer chromatography in some adipose organs of anuran amphibians. II. Liposoluble vitamins.", "content": "By means of thin layer chromatography and selective detection, vitamin A acetate, vitamin E and vitamin E acetate, vitamin D3 and cholesterol were identified in the prepericardic body, adrenal tissue, fat bodies and testis of Bubo bufo, as well as in the prepericardic body of Rana esculenta. On the contrary, liposoluble vitamins could not be isolated from the adipose tissue occurring in the thoracic cavity of Rana esculenta, or in Bufo bufo muscles. The results are discussed in correlation with the histological structure of the prepericardic body and the presumptive identification therein of steroid hormones. Lastly, the functional analogy between the prepericardic body and fat bodies in anuran amphibians and the brown adipose tissue of mammals is also postulated.", "contents": "Research on cholesterol, steroidal hormones and liposoluble vitamins by thin layer chromatography in some adipose organs of anuran amphibians. II. Liposoluble vitamins. By means of thin layer chromatography and selective detection, vitamin A acetate, vitamin E and vitamin E acetate, vitamin D3 and cholesterol were identified in the prepericardic body, adrenal tissue, fat bodies and testis of Bubo bufo, as well as in the prepericardic body of Rana esculenta. On the contrary, liposoluble vitamins could not be isolated from the adipose tissue occurring in the thoracic cavity of Rana esculenta, or in Bufo bufo muscles. The results are discussed in correlation with the histological structure of the prepericardic body and the presumptive identification therein of steroid hormones. Lastly, the functional analogy between the prepericardic body and fat bodies in anuran amphibians and the brown adipose tissue of mammals is also postulated."}
{"id": "PMID:218527", "title": "Liver resection for hepatic adenoma.", "content": "Between 1970 and 1978, eight hepatic adenomas were resected. Four of the eight patients took oral contraceptive pills before the hepatic adenoma was identified; one patient was male. Four patients had evidence of bleeding at the time of presentation. The original histologic diagnosis in the first five patients was malignant hepatoma. There has been no known recurrence of tumor and all patients are well. The use of oral contraceptives in these patients has been prohibited. Formal anatomic resection is recommended for hepatic adenoma when this procedure can be done without mortality or serious morbidity; however, in the future, less drastic treatments, such as occlusion of the hepatic arterial circulation to the tumor or discontinuation of oral contraceptives, may prove as effective as tumor resection.", "contents": "Liver resection for hepatic adenoma. Between 1970 and 1978, eight hepatic adenomas were resected. Four of the eight patients took oral contraceptive pills before the hepatic adenoma was identified; one patient was male. Four patients had evidence of bleeding at the time of presentation. The original histologic diagnosis in the first five patients was malignant hepatoma. There has been no known recurrence of tumor and all patients are well. The use of oral contraceptives in these patients has been prohibited. Formal anatomic resection is recommended for hepatic adenoma when this procedure can be done without mortality or serious morbidity; however, in the future, less drastic treatments, such as occlusion of the hepatic arterial circulation to the tumor or discontinuation of oral contraceptives, may prove as effective as tumor resection."}
{"id": "PMID:218525", "title": "Biochemical data on subtotally hypophysectomized Xenopus laevis (Daudin) adult specimens treated or not with prolactin.", "content": "Xenopus laevis (Daudin) adult specimens were submitted to hypophysectomy. Although the operation resulted subtotal, it served the purpose of removing the prolactin-producing cells, whereby the involvement of endogenous prolactin in osmoregulation phenomena was excluded. In the operated animals treated with ovine prolactin the following metabolic parameters, which are closely dependent upon interrenal activity, were estimated: 1) intestine alkaline phosphomonoesterase activity (E.C. 3.1.3.1); 2) liver glycogen level; 3) glucose-6-phosphatase (E.C. 3.1.3.9.) and phosphoenolpyruvate carboxykinase (E.C. 4.1.1.32.) in the liver; 4) blood glucose level; 5) blood ammonia and urea levels; 6) carbamoylphosphate synthetase activity in the liver (E.C. 2.7.2.a); 7) muscle sodium and potassium levels. The above metabolic parameters were found to be pressed by subtotal hypophysectomy and after subsequent prolactin treatment showed the tendency to go back to values similar to those of control animals.", "contents": "Biochemical data on subtotally hypophysectomized Xenopus laevis (Daudin) adult specimens treated or not with prolactin. Xenopus laevis (Daudin) adult specimens were submitted to hypophysectomy. Although the operation resulted subtotal, it served the purpose of removing the prolactin-producing cells, whereby the involvement of endogenous prolactin in osmoregulation phenomena was excluded. In the operated animals treated with ovine prolactin the following metabolic parameters, which are closely dependent upon interrenal activity, were estimated: 1) intestine alkaline phosphomonoesterase activity (E.C. 3.1.3.1); 2) liver glycogen level; 3) glucose-6-phosphatase (E.C. 3.1.3.9.) and phosphoenolpyruvate carboxykinase (E.C. 4.1.1.32.) in the liver; 4) blood glucose level; 5) blood ammonia and urea levels; 6) carbamoylphosphate synthetase activity in the liver (E.C. 2.7.2.a); 7) muscle sodium and potassium levels. The above metabolic parameters were found to be pressed by subtotal hypophysectomy and after subsequent prolactin treatment showed the tendency to go back to values similar to those of control animals."}
{"id": "PMID:218529", "title": "The susceptibility of cell lines of Aedes aegypti (Linn.), Aedes albopictus (Skuse) and Aedes pseudoscutellaris (Therobald) to infection with blutongue virus.", "content": "Bluetongue virus multiplied in cell lines derived from Aedes albopictus and Aedes pseudoscutellaris cells. Virus reached a maximum titre in the Ae. pseudoscutellaris cells three days post inoculation, and in Ae. albopictus cells six days p.i. Virus growth was demonstrated in both cell lines at 27 degrees C and 37 degrees C. Significant titres of virus were still present in the Ae. albopictus cells after five subcultures at 27 degrees C over a period of six weeks. No cytopathic effect was observed in either cell line. A third cell line derived from the mosquito Ae. aegypti did not support the growth of Bluetongue virus.", "contents": "The susceptibility of cell lines of Aedes aegypti (Linn.), Aedes albopictus (Skuse) and Aedes pseudoscutellaris (Therobald) to infection with blutongue virus. Bluetongue virus multiplied in cell lines derived from Aedes albopictus and Aedes pseudoscutellaris cells. Virus reached a maximum titre in the Ae. pseudoscutellaris cells three days post inoculation, and in Ae. albopictus cells six days p.i. Virus growth was demonstrated in both cell lines at 27 degrees C and 37 degrees C. Significant titres of virus were still present in the Ae. albopictus cells after five subcultures at 27 degrees C over a period of six weeks. No cytopathic effect was observed in either cell line. A third cell line derived from the mosquito Ae. aegypti did not support the growth of Bluetongue virus."}
{"id": "PMID:218530", "title": "Ultrastructural changes in small intestinal epithelium of neonatal pigs infected with pig rotavirus.", "content": "The small intestine of piglets orally infected with rotavirus was examined by electron microscopy 18, 24, 48 and 60 hours after infection. At 18 and 24 hours after infection columnar epithelial cells covered the villi. Infected epithelial cells tended to be less electron-dense than uninfected cells and were more numerous at 24 hours after infection. Two types of rotavirus particle were seen, usually within dilated cisternae of the RER: non-enveloped particles measuring 50 to 60 nm and enveloped particles measuring 65 to 75 nm. Non-membrane bound viroplasm containing electron-dense cores was encountered outside the cisternae 18 and 24 hours after infection. Tubular structures measuring 44 to 56 nm were often found in nuclei of infected cells. Single-membraned (44 to 55 nm) and double-membraned tubules (70 to 80 nm) associated with viral manufacture were found in the cytoplasm of infected cells. At 48 and 60 hours after infection a proportion of villous epithelial cells were cuboidal. Virus particles were detected in only a few epithelial cells and nuclear and cytoplasmic tubules were not seen. At all times after infection some infected cells showed a reduction in the number and size of the microvilli comprising the brush border.", "contents": "Ultrastructural changes in small intestinal epithelium of neonatal pigs infected with pig rotavirus. The small intestine of piglets orally infected with rotavirus was examined by electron microscopy 18, 24, 48 and 60 hours after infection. At 18 and 24 hours after infection columnar epithelial cells covered the villi. Infected epithelial cells tended to be less electron-dense than uninfected cells and were more numerous at 24 hours after infection. Two types of rotavirus particle were seen, usually within dilated cisternae of the RER: non-enveloped particles measuring 50 to 60 nm and enveloped particles measuring 65 to 75 nm. Non-membrane bound viroplasm containing electron-dense cores was encountered outside the cisternae 18 and 24 hours after infection. Tubular structures measuring 44 to 56 nm were often found in nuclei of infected cells. Single-membraned (44 to 55 nm) and double-membraned tubules (70 to 80 nm) associated with viral manufacture were found in the cytoplasm of infected cells. At 48 and 60 hours after infection a proportion of villous epithelial cells were cuboidal. Virus particles were detected in only a few epithelial cells and nuclear and cytoplasmic tubules were not seen. At all times after infection some infected cells showed a reduction in the number and size of the microvilli comprising the brush border."}
{"id": "PMID:218531", "title": "Further study on the three-dimensional structure of the core of Marek's disease virus and herpesvirus of turkey.", "content": "Three-dimensional structures of the core of Marek's disease virus and herpesvirus of turkey were examined by the tilting apparatus of an electron microscope. Various types of the core found in the infected cells were considered to represent developmental stages of the viruses. The basic structure of the core consisted of a toroid surrounding a cylindrical mass, which was clearly demonstrated by tilting the core in two directions. A cylindrical mass spooled by more than two toroids, which seemed to constitute a spiral band of 10 to 20 nm, was demonstrated. The maturation process of the cores of the viruses was also discussed.", "contents": "Further study on the three-dimensional structure of the core of Marek's disease virus and herpesvirus of turkey. Three-dimensional structures of the core of Marek's disease virus and herpesvirus of turkey were examined by the tilting apparatus of an electron microscope. Various types of the core found in the infected cells were considered to represent developmental stages of the viruses. The basic structure of the core consisted of a toroid surrounding a cylindrical mass, which was clearly demonstrated by tilting the core in two directions. A cylindrical mass spooled by more than two toroids, which seemed to constitute a spiral band of 10 to 20 nm, was demonstrated. The maturation process of the cores of the viruses was also discussed."}
{"id": "PMID:218532", "title": "Physical characterization of a stomatitis papulosa virus genome: a cleavage map for the restriction endonucleases HindIII and EcoRI.", "content": "The genome of stomatitis papulosa virus (a parapoxvirus) was cleaved with the restriction endonucleases HindIII and EcoRI, each giving rise to 6 fragments respectively. Double digestion with both enzymes resulted in 8 bands, two of which contained DNA fragments in double molar concentrations as revealed by reciprocal digests of isolated DNA fragments. The genome size, estimated by summation of the molecular weights of the fragments, is approximately 86 X 10(6) daltons, some 30 X 10(6) daltons smaller than vaccinia virus (an orthopoxvirus) DNA. The cleavage sites of HindIII and EcoRI endonucleases were mapped on the genome by analysis of reciprocal digests of isolated DNA fragments and by cross-hybridization experiments. This yielded two mapped segments which were then oriented relative to one another by cleavage of isolated partial digestion products. The terminal restriction fragments show rapid renaturation after alkali denaturation and subsequent neutralization, indicating that stomatitis papulosa virus DNA contains terminal cross-links analogous to those found in vaccinia virus DNA.", "contents": "Physical characterization of a stomatitis papulosa virus genome: a cleavage map for the restriction endonucleases HindIII and EcoRI. The genome of stomatitis papulosa virus (a parapoxvirus) was cleaved with the restriction endonucleases HindIII and EcoRI, each giving rise to 6 fragments respectively. Double digestion with both enzymes resulted in 8 bands, two of which contained DNA fragments in double molar concentrations as revealed by reciprocal digests of isolated DNA fragments. The genome size, estimated by summation of the molecular weights of the fragments, is approximately 86 X 10(6) daltons, some 30 X 10(6) daltons smaller than vaccinia virus (an orthopoxvirus) DNA. The cleavage sites of HindIII and EcoRI endonucleases were mapped on the genome by analysis of reciprocal digests of isolated DNA fragments and by cross-hybridization experiments. This yielded two mapped segments which were then oriented relative to one another by cleavage of isolated partial digestion products. The terminal restriction fragments show rapid renaturation after alkali denaturation and subsequent neutralization, indicating that stomatitis papulosa virus DNA contains terminal cross-links analogous to those found in vaccinia virus DNA."}
{"id": "PMID:218533", "title": "Cell mediated immunity to bovine rhinovirus type 1 in calves.", "content": "Calves experimentally infected with bovine rhinovirus type 1 developed a mild respiratory disease and exhibited a cell mediated immune (CMI) response, as determined by leukocyte migration inhibition (LMI) and lymphocyte blastogenesis tests. The CMI response to the virus was detected by day 3 post-inoculation using direct and indirect LMI tests. It persisted through day 28, with maximal responses occurring between days 4 and 14. Measurement of cellular immunity by blast transformation, however, was not evidenced until day 12. The humoral antibody response was minimal with serum neutralizing titers ranging from 1:4 to 1:16 and this response was not evident until 3 weeks after inoculation.", "contents": "Cell mediated immunity to bovine rhinovirus type 1 in calves. Calves experimentally infected with bovine rhinovirus type 1 developed a mild respiratory disease and exhibited a cell mediated immune (CMI) response, as determined by leukocyte migration inhibition (LMI) and lymphocyte blastogenesis tests. The CMI response to the virus was detected by day 3 post-inoculation using direct and indirect LMI tests. It persisted through day 28, with maximal responses occurring between days 4 and 14. Measurement of cellular immunity by blast transformation, however, was not evidenced until day 12. The humoral antibody response was minimal with serum neutralizing titers ranging from 1:4 to 1:16 and this response was not evident until 3 weeks after inoculation."}
{"id": "PMID:218534", "title": "Comparison of the morphology of three coronaviruses.", "content": "The morphology of three coronaviruses, avian infectious bronchitis virus strain Connecticut (IBV Conn), human coronavirus strain 229E (HCV 229E) and mouse hepatitis virus strain 3 (MHV3), were examined by negative staining. Significant differences were found in the sizes of the three coronaviruses. Furthermore, three types of surface projection of the same lengths, but varying widths and morphology, were observed. Both IBV Conn and HCV 229E had bulbous projections characteristic of coronaviruses, although the projections of HCV 229E were somewhat thinner than those of IBV Conn. On the other hand, MHV3 particles had thin, cone-shaped surface projections, that were completely unlike typical coronavirus projections. The significance of these results is discussed.", "contents": "Comparison of the morphology of three coronaviruses. The morphology of three coronaviruses, avian infectious bronchitis virus strain Connecticut (IBV Conn), human coronavirus strain 229E (HCV 229E) and mouse hepatitis virus strain 3 (MHV3), were examined by negative staining. Significant differences were found in the sizes of the three coronaviruses. Furthermore, three types of surface projection of the same lengths, but varying widths and morphology, were observed. Both IBV Conn and HCV 229E had bulbous projections characteristic of coronaviruses, although the projections of HCV 229E were somewhat thinner than those of IBV Conn. On the other hand, MHV3 particles had thin, cone-shaped surface projections, that were completely unlike typical coronavirus projections. The significance of these results is discussed."}
{"id": "PMID:218535", "title": "Loss of virulence in a small plaque mutant of the infectious bursal disease virus.", "content": "A variant strain Cu-1 M was established from the infectious bursal disease virus strain Cu-1. This variant strain forms smaller plaques than the wild type; it has a retarded growth rate, does not lead to an overt disease in chickens and causes only minor lesions in the bursa of Fabricius. Infection with this strain induces solid protective immunity against infection with the virulent virus.", "contents": "Loss of virulence in a small plaque mutant of the infectious bursal disease virus. A variant strain Cu-1 M was established from the infectious bursal disease virus strain Cu-1. This variant strain forms smaller plaques than the wild type; it has a retarded growth rate, does not lead to an overt disease in chickens and causes only minor lesions in the bursa of Fabricius. Infection with this strain induces solid protective immunity against infection with the virulent virus."}
{"id": "PMID:218536", "title": "Structural polypeptides of the enteropathogenic bovine coronavirus strain LY-138.", "content": "The bovine coronavirus strain LY-138 was purified by differential as well as velocity and isopycnic centrifugation in sucrose or CsCl gradients. The substrate for purification was contents of the small intestine of experimentally inoculated calves. This strain is highly enteropathogenic, but it could not yet be propagated in cultured cells. Intact virions had a density of 1.245 g/cm3 in CsCl and 1.185 g/cm3 in sucrose. A spherical core-like structure with an average diameter of 82 nm remaining after treatment with chloroform had a density of 1.299 g/cm3 in CsCl and 1.201 g/cm3 in sucrose. Seven distinct bands of polypeptides and 4 shoulders were detected after electrophoresis of SDS-solubilized virions in polyacrylamide gels. The approximate molecular weights ranged from 110,000 to 36,000. Four of the bands gave a PAS positive reaction. These 4 glycoproteins and an additional protein with an approximate molecular weight of 70,000 were removed by chloroform treatment. The remaining core-like structure contained the 2 polypeptides VP3 and VP7.", "contents": "Structural polypeptides of the enteropathogenic bovine coronavirus strain LY-138. The bovine coronavirus strain LY-138 was purified by differential as well as velocity and isopycnic centrifugation in sucrose or CsCl gradients. The substrate for purification was contents of the small intestine of experimentally inoculated calves. This strain is highly enteropathogenic, but it could not yet be propagated in cultured cells. Intact virions had a density of 1.245 g/cm3 in CsCl and 1.185 g/cm3 in sucrose. A spherical core-like structure with an average diameter of 82 nm remaining after treatment with chloroform had a density of 1.299 g/cm3 in CsCl and 1.201 g/cm3 in sucrose. Seven distinct bands of polypeptides and 4 shoulders were detected after electrophoresis of SDS-solubilized virions in polyacrylamide gels. The approximate molecular weights ranged from 110,000 to 36,000. Four of the bands gave a PAS positive reaction. These 4 glycoproteins and an additional protein with an approximate molecular weight of 70,000 were removed by chloroform treatment. The remaining core-like structure contained the 2 polypeptides VP3 and VP7."}
{"id": "PMID:218537", "title": "Differences in antibody responses in varicella, herpes zoster and after vaccination.", "content": "Difference in antibody responses between varicella and herpes zoster was reconfirmed by complement fixation (CF) test and by platelet aggregation (PA) test. Rise in PA antibody level was observed only in patients with herpes zoster, but not in patients with varicella, while the increase in CF antibody was demonstrated in both types of the diseases. Among 235 healthy children, CF antibody was detected in 42 children and out of these 25 also had PA antibody. Sera of 116 individuals who were vaccinated with a live vaccine comprised of varicella-herpes zoster virus (VZV) were tested for CF and PA antibodies. Within six months after vaccination, 81.3 per cent of the vaccinees demonstrated the rise in CF antibody alone, and only one vaccinee possessed low level of PA antibody. Six months to 1 year after vaccination, CF antibody in 12 out of 13 vaccinees fell to undetectable level. Later than 1 year after vaccination, 9 out of 28 vaccinees possessed CF antibody. Two out of these 9 vaccinees also had PA antibody. The PA antigens prepared from viruses isolated either from a varicella patient or a herpes zoster patient responded similarly to the sera of herpes zoster patients, but no response was detected with sera of varicella patients. PA and CF antibody titers of herpes zoster patients showed a high degree of correlation.", "contents": "Differences in antibody responses in varicella, herpes zoster and after vaccination. Difference in antibody responses between varicella and herpes zoster was reconfirmed by complement fixation (CF) test and by platelet aggregation (PA) test. Rise in PA antibody level was observed only in patients with herpes zoster, but not in patients with varicella, while the increase in CF antibody was demonstrated in both types of the diseases. Among 235 healthy children, CF antibody was detected in 42 children and out of these 25 also had PA antibody. Sera of 116 individuals who were vaccinated with a live vaccine comprised of varicella-herpes zoster virus (VZV) were tested for CF and PA antibodies. Within six months after vaccination, 81.3 per cent of the vaccinees demonstrated the rise in CF antibody alone, and only one vaccinee possessed low level of PA antibody. Six months to 1 year after vaccination, CF antibody in 12 out of 13 vaccinees fell to undetectable level. Later than 1 year after vaccination, 9 out of 28 vaccinees possessed CF antibody. Two out of these 9 vaccinees also had PA antibody. The PA antigens prepared from viruses isolated either from a varicella patient or a herpes zoster patient responded similarly to the sera of herpes zoster patients, but no response was detected with sera of varicella patients. PA and CF antibody titers of herpes zoster patients showed a high degree of correlation."}
{"id": "PMID:218538", "title": "Stability and immunogenicity of empty particles of foot-and-mouth disease virus.", "content": "Three strains of foot-and-mouth disease virus were shown to contain significant amounts of naturally occurring 75S, empty particles as well as the infectious, 140S full particles. One of these strains--A Pando (1970)--was studied in detail. The empty particles from this virus strain were shown to have an observed sedimentation coefficient of 67S in 0.04 M phosphate buffer; they were labile in SDS, non-infectious and probably RNA-free and, on heating, they broke down to 12S subunits as did the 140S particles. The empty particles differed from the full particles in their polypeptide composition since they contained VP0, but there was no evidence for a diminished content of VP4. The 75S particles were shown to be present in significant amounts and to be stable to AEI inactivation. At 4 degrees C they were stable for at least two years. In guinea pigs they were as immunogenic as the 140S particles. The antisera raised against the 75S particles had the same serological specificity in neutralization tests as sera prepared against the 140S particle. It was concluded that the 75S particles from the A Pando (1970) strain of FMD virus may provide as important a contribution as 140S particles to the immunogenicity of inactivated vaccines prepared from this virus strain.", "contents": "Stability and immunogenicity of empty particles of foot-and-mouth disease virus. Three strains of foot-and-mouth disease virus were shown to contain significant amounts of naturally occurring 75S, empty particles as well as the infectious, 140S full particles. One of these strains--A Pando (1970)--was studied in detail. The empty particles from this virus strain were shown to have an observed sedimentation coefficient of 67S in 0.04 M phosphate buffer; they were labile in SDS, non-infectious and probably RNA-free and, on heating, they broke down to 12S subunits as did the 140S particles. The empty particles differed from the full particles in their polypeptide composition since they contained VP0, but there was no evidence for a diminished content of VP4. The 75S particles were shown to be present in significant amounts and to be stable to AEI inactivation. At 4 degrees C they were stable for at least two years. In guinea pigs they were as immunogenic as the 140S particles. The antisera raised against the 75S particles had the same serological specificity in neutralization tests as sera prepared against the 140S particle. It was concluded that the 75S particles from the A Pando (1970) strain of FMD virus may provide as important a contribution as 140S particles to the immunogenicity of inactivated vaccines prepared from this virus strain."}
{"id": "PMID:218539", "title": "Enhanced antiglobulin-mediated neutralization of herpes simplex virus-IgG complexes by complement and heterologous anti-immunoglobulin.", "content": "The ability of IgG anti-Fc and anti-Fab to neutralize infectious herpes simplex virus-IgG (HSV-IgG) complexes was determined. When limiting amounts of antiglobulin were used, antibody directed against the Fab portion of human IgG was significantly more effective than anti-Fc antibodies in neutralizing the HSV-IgG complexes. The detection of viral bound antibody was enhanced by the incorporation of heterologous antiglobulin or complement in the antiglobulin neutralization test. Specifically, HSV-IgG which had been incubated with rabbit antihuman globulin was further neutralized by goat antirabbit IgG or guinea pig serum complement. This augmented neutralization test could prove useful in detecting small amounts of antibody bound to virus in infectious isolates from patients or experimental animals with viral diseases.", "contents": "Enhanced antiglobulin-mediated neutralization of herpes simplex virus-IgG complexes by complement and heterologous anti-immunoglobulin. The ability of IgG anti-Fc and anti-Fab to neutralize infectious herpes simplex virus-IgG (HSV-IgG) complexes was determined. When limiting amounts of antiglobulin were used, antibody directed against the Fab portion of human IgG was significantly more effective than anti-Fc antibodies in neutralizing the HSV-IgG complexes. The detection of viral bound antibody was enhanced by the incorporation of heterologous antiglobulin or complement in the antiglobulin neutralization test. Specifically, HSV-IgG which had been incubated with rabbit antihuman globulin was further neutralized by goat antirabbit IgG or guinea pig serum complement. This augmented neutralization test could prove useful in detecting small amounts of antibody bound to virus in infectious isolates from patients or experimental animals with viral diseases."}
{"id": "PMID:218540", "title": "Amyotrophic lateral sclerosis. Impairment of neuromuscular transmission.", "content": "Neuromuscular transmission was studied in the ulnar-hypothenar group in 55 patients with amyotrophic lateral sclerosis. A decremental response was found in 67.0%. The decrement was larger and present more often in muscles showing atrophy. In addition, muscles with frequent fasciculations showed a larger decrement than the ones with rare fasciculation. A temperature effect similar to that in myasthenia gravis was observed, with a reduction of the decrement following local cooling of the muscles. Administration of edrophonium chloride improved the synaptic defect. Posttetanic exhaustion was observed as well. It is thought that the defect of neuromuscular transmission is due to a decreased trophic function of the neuron followed by morphological changes at the endplate.", "contents": "Amyotrophic lateral sclerosis. Impairment of neuromuscular transmission. Neuromuscular transmission was studied in the ulnar-hypothenar group in 55 patients with amyotrophic lateral sclerosis. A decremental response was found in 67.0%. The decrement was larger and present more often in muscles showing atrophy. In addition, muscles with frequent fasciculations showed a larger decrement than the ones with rare fasciculation. A temperature effect similar to that in myasthenia gravis was observed, with a reduction of the decrement following local cooling of the muscles. Administration of edrophonium chloride improved the synaptic defect. Posttetanic exhaustion was observed as well. It is thought that the defect of neuromuscular transmission is due to a decreased trophic function of the neuron followed by morphological changes at the endplate."}
{"id": "PMID:218541", "title": "Facial myokymia. Pathological features.", "content": "Pathologic examination in a case of facial myokymia showed edema and mild astroglial proliferation of the ipsilateral seventh nerve nucleus; gliomatous tumor involvement occurred rostral to this nucleus. These findings give circumstantial support to functional deafferentation as the cause of facial myokymia.", "contents": "Facial myokymia. Pathological features. Pathologic examination in a case of facial myokymia showed edema and mild astroglial proliferation of the ipsilateral seventh nerve nucleus; gliomatous tumor involvement occurred rostral to this nucleus. These findings give circumstantial support to functional deafferentation as the cause of facial myokymia."}
{"id": "PMID:218542", "title": "Clostridium perfringens corneal ulcer.", "content": "A corneal ulcer caused by Clostridium perfringens developed in a 76-year-old woman with Sj\u00f6gren's syndrome. Experimental C perfringens keratitis was induced in rabbits by the intrastromal injection of 10(7) organisms. In both our patient and the experimental animals, a bullous lesion overlay the affected area of the cornea. This may be a specific lesion in clostridial infections of the cornea. Clostridium perfringens should be regarded as an opportunistic corneal pathogen, and anaerobic cultures should be performed in all cases of suspected bacterial corneal ulcer.", "contents": "Clostridium perfringens corneal ulcer. A corneal ulcer caused by Clostridium perfringens developed in a 76-year-old woman with Sj\u00f6gren's syndrome. Experimental C perfringens keratitis was induced in rabbits by the intrastromal injection of 10(7) organisms. In both our patient and the experimental animals, a bullous lesion overlay the affected area of the cornea. This may be a specific lesion in clostridial infections of the cornea. Clostridium perfringens should be regarded as an opportunistic corneal pathogen, and anaerobic cultures should be performed in all cases of suspected bacterial corneal ulcer."}
{"id": "PMID:218543", "title": "Congenital fibrous lesion of the temporal bone.", "content": "A neonate had a destructive, fibrous lesion of the temporal bone. There was x-ray evidence of disseminated, lytic disease. A histologic diagnosis of malignant fibrous histiocytoma was made. No treatment was given, yet the child survived with spontaneous resolution of her lesions. We briefly discuss malignant fibrous histiocytoma and propose congenital generalized fibromatosis as an alternative diagnosis to explain the child's recovery.", "contents": "Congenital fibrous lesion of the temporal bone. A neonate had a destructive, fibrous lesion of the temporal bone. There was x-ray evidence of disseminated, lytic disease. A histologic diagnosis of malignant fibrous histiocytoma was made. No treatment was given, yet the child survived with spontaneous resolution of her lesions. We briefly discuss malignant fibrous histiocytoma and propose congenital generalized fibromatosis as an alternative diagnosis to explain the child's recovery."}
{"id": "PMID:218544", "title": "Alcoholic neuropathies.", "content": "Peripheral neuropathy is a common and potentially incapacitating complication of prolonged overuse of alcohol. As a relatively early feature of chronic alcoholism, its early identification is of value in the prevention of other and more dangerous consequences of alcohol abuse. With vigilance, peripheral neuropathy is easily diagnosed before gross incapacity has resulted, but its management entails all the problems encountered in the treatment of chronic alcoholism.", "contents": "Alcoholic neuropathies. Peripheral neuropathy is a common and potentially incapacitating complication of prolonged overuse of alcohol. As a relatively early feature of chronic alcoholism, its early identification is of value in the prevention of other and more dangerous consequences of alcohol abuse. With vigilance, peripheral neuropathy is easily diagnosed before gross incapacity has resulted, but its management entails all the problems encountered in the treatment of chronic alcoholism."}
{"id": "PMID:218550", "title": "Thyroid-hormone modulation of the number of beta-adrenergic receptors in rat fat-cell membranes.", "content": "Adipocytes from thyroidectomized rats contain 3 times less [3H]dihydroalprenolol-binding sites (beta-adrenergic receptors) than adipocytes from euthyroid animals. This alteration is not solely due to cell-size differences, but also to a thyroidectomy-induced defect in beta-adrenergic receptor density per adipocyte surface area, a defect that is furthermore corrected by tri-iodothyronine treatment.", "contents": "Thyroid-hormone modulation of the number of beta-adrenergic receptors in rat fat-cell membranes. Adipocytes from thyroidectomized rats contain 3 times less [3H]dihydroalprenolol-binding sites (beta-adrenergic receptors) than adipocytes from euthyroid animals. This alteration is not solely due to cell-size differences, but also to a thyroidectomy-induced defect in beta-adrenergic receptor density per adipocyte surface area, a defect that is furthermore corrected by tri-iodothyronine treatment."}
{"id": "PMID:218547", "title": "Changes in cAMP concentrations during chronic cardiac hypertrophy.", "content": "Mild pulmonic stenosis in the dog, where right ventricular peak systolic pressure was increased approximately 150% at the time of sacrifice, induced 100% or more increase in right ventricular free wall weight by 3 weeks postoperative. Accompanying cardiac hypertrophy at these postoperative times, there was a decrease in both tissue PO2 levels and cAMP concentrations in the hemodynamically stressed ventricle, the right ventricle. Myosin ATPase activity was elevated as well as the velocity of contractile element shortening. The hemodynamically nonstressed left ventricle did not hypertrophy at these early postoperative times.", "contents": "Changes in cAMP concentrations during chronic cardiac hypertrophy. Mild pulmonic stenosis in the dog, where right ventricular peak systolic pressure was increased approximately 150% at the time of sacrifice, induced 100% or more increase in right ventricular free wall weight by 3 weeks postoperative. Accompanying cardiac hypertrophy at these postoperative times, there was a decrease in both tissue PO2 levels and cAMP concentrations in the hemodynamically stressed ventricle, the right ventricle. Myosin ATPase activity was elevated as well as the velocity of contractile element shortening. The hemodynamically nonstressed left ventricle did not hypertrophy at these early postoperative times."}
{"id": "PMID:218551", "title": "Growth and metabolism of fucosylated plasma-membrane glycoproteins in mouse neuroblastoma N2a cells.", "content": "The presence of 1.0mm-dibutyryl cyclic AMP (N(6),O(2')-dibutyryladenosine 3':5'-cyclic monophosphate) and 1.5mm-theophylline completely inhibits the growth of mouse neuroblastoma N2a cells by 24-36h. When compared with N2a cultures without inhibitors (controls), the proportion of cells in S phase, measured by radioautography with [(3)H]-thymidine, was decreased from 55 to 12%. In addition, the presence of the inhibitors decreased apparent [(3)H]fucose incorporation into glycoproteins by 50%, and removing the inhibitors resulted in a rapid recovery of both DNA synthesis and glycoprotein metabolism. Measurement of intracellular acid-soluble radioactive fucose revealed that decreased fucose uptake could account for the apparent change in incorporation. Removing dibutyryl cyclic AMP and theophylline from the medium resulted in a rapid uptake of radioactive fucose to within control values, which illustrated that the inhibitors decreased transport of the carbohydrate, although the cells remained viable. Treatment with dibutyryl cyclic AMP and theophylline also reversibly inhibited glycoprotein degradation. Plasma membranes isolated from growing cells and from growth-inhibited cells labelled with [(14)C]fucose and [(3)H]fucose respectively were co-electrophoresed on sodium dodecyl sulphate/polyacrylamide gels. These displayed no apparent differences in synthesis of specific membrane glycoproteins. Electrophoresis of plasma membranes isolated from cultures pulse-chased with [(14)C]fucose and [(3)H]fucose was used to discern turnover patterns of specific plasma-membrane glycoproteins. High-molecular-weight glycoproteins exhibited rapid rates of turnover in membranes from growing cells, but moderate turnover rates in growth-inhibited cells and cells reversed from growth inhibition. These data indicate that growth arrest of N2a cells results in alterations in the metabolic turnover of plasma-membrane glycoproteins.", "contents": "Growth and metabolism of fucosylated plasma-membrane glycoproteins in mouse neuroblastoma N2a cells. The presence of 1.0mm-dibutyryl cyclic AMP (N(6),O(2')-dibutyryladenosine 3':5'-cyclic monophosphate) and 1.5mm-theophylline completely inhibits the growth of mouse neuroblastoma N2a cells by 24-36h. When compared with N2a cultures without inhibitors (controls), the proportion of cells in S phase, measured by radioautography with [(3)H]-thymidine, was decreased from 55 to 12%. In addition, the presence of the inhibitors decreased apparent [(3)H]fucose incorporation into glycoproteins by 50%, and removing the inhibitors resulted in a rapid recovery of both DNA synthesis and glycoprotein metabolism. Measurement of intracellular acid-soluble radioactive fucose revealed that decreased fucose uptake could account for the apparent change in incorporation. Removing dibutyryl cyclic AMP and theophylline from the medium resulted in a rapid uptake of radioactive fucose to within control values, which illustrated that the inhibitors decreased transport of the carbohydrate, although the cells remained viable. Treatment with dibutyryl cyclic AMP and theophylline also reversibly inhibited glycoprotein degradation. Plasma membranes isolated from growing cells and from growth-inhibited cells labelled with [(14)C]fucose and [(3)H]fucose respectively were co-electrophoresed on sodium dodecyl sulphate/polyacrylamide gels. These displayed no apparent differences in synthesis of specific membrane glycoproteins. Electrophoresis of plasma membranes isolated from cultures pulse-chased with [(14)C]fucose and [(3)H]fucose was used to discern turnover patterns of specific plasma-membrane glycoproteins. High-molecular-weight glycoproteins exhibited rapid rates of turnover in membranes from growing cells, but moderate turnover rates in growth-inhibited cells and cells reversed from growth inhibition. These data indicate that growth arrest of N2a cells results in alterations in the metabolic turnover of plasma-membrane glycoproteins."}
{"id": "PMID:218552", "title": "Calcium-dependent protein modulator of cyclic nucleotide phosphodiesterases from mouse epidermis.", "content": "1. A heat-stable modulator protein was partially purified from mouse epidermis. The protein stimulated modulator-depleted cyclic AMP phosphodiesterase from bovine brain in the presence of Ca2+. 2. DEAE-cellulose chromatography of epidermal extracts demonstrated the presence of two main phosphodiesterase activities that hydrolysed both cyclic AMP and cyclic GMP. A minor peak was eluted between 0.1 and 0.3 M-sodium acetate and a major peak was eluted between 0.3 and 0.45 M-sodium acetate. 3. Cyclic AMP phosphodiesterase activity eluted at low salt concentrations was markedly activated by the epidermal modulator protein in the presence of Ca2+. Storage of the enzyme led to a decrease in its sensitivity to the protein modulator. 4. Treatment of mouse skin with the tumour promoter 12-O-tetradecanoylphorbol 13-acetate, which leads to an increase in epidermal cyclic nucleotide phosphodiesterase activity, did not alter the amount of modulator present in soluble epidermal extracts. The tumour promoter decreased the amount of modulator extractable from particulate epidermal preparations with Triton X-100.", "contents": "Calcium-dependent protein modulator of cyclic nucleotide phosphodiesterases from mouse epidermis. 1. A heat-stable modulator protein was partially purified from mouse epidermis. The protein stimulated modulator-depleted cyclic AMP phosphodiesterase from bovine brain in the presence of Ca2+. 2. DEAE-cellulose chromatography of epidermal extracts demonstrated the presence of two main phosphodiesterase activities that hydrolysed both cyclic AMP and cyclic GMP. A minor peak was eluted between 0.1 and 0.3 M-sodium acetate and a major peak was eluted between 0.3 and 0.45 M-sodium acetate. 3. Cyclic AMP phosphodiesterase activity eluted at low salt concentrations was markedly activated by the epidermal modulator protein in the presence of Ca2+. Storage of the enzyme led to a decrease in its sensitivity to the protein modulator. 4. Treatment of mouse skin with the tumour promoter 12-O-tetradecanoylphorbol 13-acetate, which leads to an increase in epidermal cyclic nucleotide phosphodiesterase activity, did not alter the amount of modulator present in soluble epidermal extracts. The tumour promoter decreased the amount of modulator extractable from particulate epidermal preparations with Triton X-100."}
{"id": "PMID:218553", "title": "The effects of cortisol, corticotropin and thyroxine on the synthesis of glycerolipids and on the phosphatidate phosphohydrolase activity in rat liver.", "content": "1. Male rats were injected daily for 5 days with 0.15m-NaCl, corticotropin, cortisol or l-thyroxine and the rates of glycerolipid synthesis were measured in the livers after intraportal injection of [(14)C]palmitate and [(3)H]glycerol. 2. Injection of all three hormones decreased the rates of body-weight gain. 3. Cortisol treatment increased the weight of the liver relative to body weight. 4. Thyroxine treatment increased the relative rate of triacylglycerol synthesis from [(3)H]glycerol and decreased the relative accumulation of (3)H and (14)C in diacylglycerol. It did not significantly alter the accumulation of these isotopes in phosphatidate nor the activity of the soluble phosphatidate phosphohydrolase in the total liver. However, this activity increased by 1.5-fold when expressed relative to the soluble protein of the liver. The increased triacylglycerol synthesis appears to be related to a general increase in the turnover of fatty acids in the liver. 5. Treatment with cortisol and corticotropin increased the relative rate of triacylglycerol synthesis from [(3)H]glycerol, decreased the accumulation of (3)H in phosphatidate and increased the flux of both isotopes from phosphatidate to diacylglycerol. This appeared to be caused by the increased activity of the soluble phosphatidate phosphohydrolase that was observed in the livers of the cortisol-treated rats. 6. It is proposed that cortisol could be directly or indirectly involved in increasing the activity of hepatic phosphatidate phosphohydrolase in starvation, diabetes, laparotomy, subtotal hepatectomy, liver damage, ethanol feeding and in obesity. This enzyme adaptation could contribute to the potential of the liver to increase its synthesis and accumulation of triacylglycerols or to secrete very-low-density lipoproteins.", "contents": "The effects of cortisol, corticotropin and thyroxine on the synthesis of glycerolipids and on the phosphatidate phosphohydrolase activity in rat liver. 1. Male rats were injected daily for 5 days with 0.15m-NaCl, corticotropin, cortisol or l-thyroxine and the rates of glycerolipid synthesis were measured in the livers after intraportal injection of [(14)C]palmitate and [(3)H]glycerol. 2. Injection of all three hormones decreased the rates of body-weight gain. 3. Cortisol treatment increased the weight of the liver relative to body weight. 4. Thyroxine treatment increased the relative rate of triacylglycerol synthesis from [(3)H]glycerol and decreased the relative accumulation of (3)H and (14)C in diacylglycerol. It did not significantly alter the accumulation of these isotopes in phosphatidate nor the activity of the soluble phosphatidate phosphohydrolase in the total liver. However, this activity increased by 1.5-fold when expressed relative to the soluble protein of the liver. The increased triacylglycerol synthesis appears to be related to a general increase in the turnover of fatty acids in the liver. 5. Treatment with cortisol and corticotropin increased the relative rate of triacylglycerol synthesis from [(3)H]glycerol, decreased the accumulation of (3)H in phosphatidate and increased the flux of both isotopes from phosphatidate to diacylglycerol. This appeared to be caused by the increased activity of the soluble phosphatidate phosphohydrolase that was observed in the livers of the cortisol-treated rats. 6. It is proposed that cortisol could be directly or indirectly involved in increasing the activity of hepatic phosphatidate phosphohydrolase in starvation, diabetes, laparotomy, subtotal hepatectomy, liver damage, ethanol feeding and in obesity. This enzyme adaptation could contribute to the potential of the liver to increase its synthesis and accumulation of triacylglycerols or to secrete very-low-density lipoproteins."}
{"id": "PMID:218554", "title": "Responsiveness to glucagon by isolated rat hepatocytes controlled by the redox state of the cytosolic nicotinamide--adenine dinucleotide couple acting on adenosine 3':5'-cyclic monophosphate phosphodiesterase.", "content": "1. The effects of changes in the cytoplasmic [NADH]/[NAD+] ratio on the efficacy of glucagon to alter rates of metabolism in isolated rat hepatocytes were examined. 2. Under reduced conditions (with 10mM-lactate), 10nM-glucagon stimulated both gluconeogenesis and urea synthesis in isolated hepatocytes from 48h-starved rats; under oxidized conditions (with 10mM-pyruvate), 10nM-glucagon had no effect on either of these rates. 3. The ability of glucagon to alter the concentration of 3':5'-cyclic AMP and the rates of glucose output, glycogen breakdown and glycolysis in cells from fed rats were each affected by a change in the extracellular [lactate]/[pyruvate] ratio; minimal effects of glucagon occurred at low [lactate]/[pyruvate] ratios. 4. Dose-response curves for glucagon-mediated changes in cyclic AMP concentration and glucose output indicated that under oxidized conditions the ability of glucagon to alter each parameter was decreased without affecting the concentration of hormone at which half-maximal effects occurred. 5. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (0.05 mM) significantly reversed the inhibitory effects of pyruvate on glucagon-stimulated glucose output. 6. For exogenously added cyclic [3H]AMP(0.1 mM), oxidized conditions decreased the stimulatory effect on glucose output as well as the intracellular concentration of cyclic AMP attained, but did not alter the amount of cyclic [3H]AMP taken up. 7. The effects of lactate, pyruvate, NAD+ and NADH on cyclic AMP phosphodiesterase activities of rat hepatocytes were examined. 8. NADH (0.01--1 MM) inhibited the low-Km enzyme, particularly that which was associated with the plasma membrane. 9. The inhibition of membrane-bound cyclic AMP phosphodiesterase by NADH was specific, reversible and resulted in a decrease in the maximal velocity of the enzyme. 10. It is proposed that regulation of the membrane-bound low-Km cyclic AMP phosphodiesterase by nicotinamide nucleotides provides the molecular basis for the effect of redox state on the hormonal control of hepatocyte metabolism by glucagon.", "contents": "Responsiveness to glucagon by isolated rat hepatocytes controlled by the redox state of the cytosolic nicotinamide--adenine dinucleotide couple acting on adenosine 3':5'-cyclic monophosphate phosphodiesterase. 1. The effects of changes in the cytoplasmic [NADH]/[NAD+] ratio on the efficacy of glucagon to alter rates of metabolism in isolated rat hepatocytes were examined. 2. Under reduced conditions (with 10mM-lactate), 10nM-glucagon stimulated both gluconeogenesis and urea synthesis in isolated hepatocytes from 48h-starved rats; under oxidized conditions (with 10mM-pyruvate), 10nM-glucagon had no effect on either of these rates. 3. The ability of glucagon to alter the concentration of 3':5'-cyclic AMP and the rates of glucose output, glycogen breakdown and glycolysis in cells from fed rats were each affected by a change in the extracellular [lactate]/[pyruvate] ratio; minimal effects of glucagon occurred at low [lactate]/[pyruvate] ratios. 4. Dose-response curves for glucagon-mediated changes in cyclic AMP concentration and glucose output indicated that under oxidized conditions the ability of glucagon to alter each parameter was decreased without affecting the concentration of hormone at which half-maximal effects occurred. 5. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (0.05 mM) significantly reversed the inhibitory effects of pyruvate on glucagon-stimulated glucose output. 6. For exogenously added cyclic [3H]AMP(0.1 mM), oxidized conditions decreased the stimulatory effect on glucose output as well as the intracellular concentration of cyclic AMP attained, but did not alter the amount of cyclic [3H]AMP taken up. 7. The effects of lactate, pyruvate, NAD+ and NADH on cyclic AMP phosphodiesterase activities of rat hepatocytes were examined. 8. NADH (0.01--1 MM) inhibited the low-Km enzyme, particularly that which was associated with the plasma membrane. 9. The inhibition of membrane-bound cyclic AMP phosphodiesterase by NADH was specific, reversible and resulted in a decrease in the maximal velocity of the enzyme. 10. It is proposed that regulation of the membrane-bound low-Km cyclic AMP phosphodiesterase by nicotinamide nucleotides provides the molecular basis for the effect of redox state on the hormonal control of hepatocyte metabolism by glucagon."}
{"id": "PMID:218555", "title": "Control of amylase biosynthesis and release in the parotid gland of the rat.", "content": "1. Amylase biosynthesis and release in the rat parotid were studied under various conditions. Incorporation of [(3)H]leucine into amylase, extracted from the tissue by immunoadsorbent, was measured and found to be time-dependent and totally inhibited by the protein synthesis inhibitor puromycin. 2. Adrenaline, at a concentration (10mum) that gave maximum stimulation of release, inhibited [(3)H]leucine incorporation into both total protein and amylase. This effect was reversed by phentolamine. 3. Adrenaline (1mum) and isoproterenol (10mum) stimulated biosynthesis of total protein and amylase. These effects were blocked by propranolol, as were the effects on release. Dibutyryl cyclic AMP (2mm) mimicked the effects of isoproterenol and adrenaline (1mum) on both amylase biosynthesis and release. All the above stimulatory effects on amylase biosynthesis were only observed if the tissue was pretreated with effector before pulse-labelling with [(3)H]leucine. 4. Insulin (625muunits/ml initial concentration, 150muunits/ml final concentration) stimulated incorporation of [(3)H]leucine into total protein and amylase when added to the tissue at the same time as the leucine. 5. Carbamoylcholine (10mum) decreased [(3)H]leucine incorporation into total protein and amylase when both were added to the tissue simultaneously, but this effect was prevented by removal of effector and washing the tissue before addition of [(3)H]leucine. 6. Stimulation of beta-adrenergic receptors increased both amylase release and biosynthesis, but stimulation of alpha-receptors can inhibit biosynthesis without inhibiting release. Cholinergic agents can also inhibit amylase biosynthesis, but stimulate release. Insulin at approximately physiological concentration can increase incorporation of leucine into amylase without stimulating release. The system described therefore provides an excellent model for the further investigation of the mechanisms of these diverse effects.", "contents": "Control of amylase biosynthesis and release in the parotid gland of the rat. 1. Amylase biosynthesis and release in the rat parotid were studied under various conditions. Incorporation of [(3)H]leucine into amylase, extracted from the tissue by immunoadsorbent, was measured and found to be time-dependent and totally inhibited by the protein synthesis inhibitor puromycin. 2. Adrenaline, at a concentration (10mum) that gave maximum stimulation of release, inhibited [(3)H]leucine incorporation into both total protein and amylase. This effect was reversed by phentolamine. 3. Adrenaline (1mum) and isoproterenol (10mum) stimulated biosynthesis of total protein and amylase. These effects were blocked by propranolol, as were the effects on release. Dibutyryl cyclic AMP (2mm) mimicked the effects of isoproterenol and adrenaline (1mum) on both amylase biosynthesis and release. All the above stimulatory effects on amylase biosynthesis were only observed if the tissue was pretreated with effector before pulse-labelling with [(3)H]leucine. 4. Insulin (625muunits/ml initial concentration, 150muunits/ml final concentration) stimulated incorporation of [(3)H]leucine into total protein and amylase when added to the tissue at the same time as the leucine. 5. Carbamoylcholine (10mum) decreased [(3)H]leucine incorporation into total protein and amylase when both were added to the tissue simultaneously, but this effect was prevented by removal of effector and washing the tissue before addition of [(3)H]leucine. 6. Stimulation of beta-adrenergic receptors increased both amylase release and biosynthesis, but stimulation of alpha-receptors can inhibit biosynthesis without inhibiting release. Cholinergic agents can also inhibit amylase biosynthesis, but stimulate release. Insulin at approximately physiological concentration can increase incorporation of leucine into amylase without stimulating release. The system described therefore provides an excellent model for the further investigation of the mechanisms of these diverse effects."}
{"id": "PMID:218556", "title": "Mechanisms for the effects of ethanol on hepatic phosphatidate phosphohydrolase.", "content": "1. The effects of the intramuscular administration of glycerol and dihydroxyacetone (40mmol per kg body wt.), sorbitol and glucose (20mmol per kg body wt.) or NaCl (1.5mmol per kg body wt. in 10ml of water per kg body wt.) were investigated on soluble phosphatidate phosphohydrolase and certain metabolites in rat liver. 2. The effects of ethanol and glycerol on phosphatidate phosphohydrolase were also studied in isolated perfused livers. 3. The administration of glycerol, sorbitol and dihydroxyacetone in vivo increased hepatic phosphatidate phosphohydrolase activity by 137, 63 and 32% respectively in 4h. 4. A significant positive correlation was found between the hepatic sn-glycerol 3-phosphate concentration and phosphatidate phosphohydrolase after the administration of various substrates in vivo. 5. The soluble phosphatidate phosphohydrolase activity tended to increase during perfusions of isolated rat livers without added substrates, and neither ethanol nor glycerol produced additional effects. 6. The activity of soluble phosphatidate phosphohydrolase was 2.5 times higher in the livers of hyperthyroid rats than in normal rats. This activity was not influenced by intragastric ethanol or glycerol administration, nor was the concentration of sn-glycerol 3-phosphate changed by these compounds. 7. It is concluded that the ethanol-induced increase in hepatic phosphatidate phosphohydrolase may at least in part be mediated by the hepatic concentration of metabolites, probably by the concentration of sn-glycerol 3-phosphate.", "contents": "Mechanisms for the effects of ethanol on hepatic phosphatidate phosphohydrolase. 1. The effects of the intramuscular administration of glycerol and dihydroxyacetone (40mmol per kg body wt.), sorbitol and glucose (20mmol per kg body wt.) or NaCl (1.5mmol per kg body wt. in 10ml of water per kg body wt.) were investigated on soluble phosphatidate phosphohydrolase and certain metabolites in rat liver. 2. The effects of ethanol and glycerol on phosphatidate phosphohydrolase were also studied in isolated perfused livers. 3. The administration of glycerol, sorbitol and dihydroxyacetone in vivo increased hepatic phosphatidate phosphohydrolase activity by 137, 63 and 32% respectively in 4h. 4. A significant positive correlation was found between the hepatic sn-glycerol 3-phosphate concentration and phosphatidate phosphohydrolase after the administration of various substrates in vivo. 5. The soluble phosphatidate phosphohydrolase activity tended to increase during perfusions of isolated rat livers without added substrates, and neither ethanol nor glycerol produced additional effects. 6. The activity of soluble phosphatidate phosphohydrolase was 2.5 times higher in the livers of hyperthyroid rats than in normal rats. This activity was not influenced by intragastric ethanol or glycerol administration, nor was the concentration of sn-glycerol 3-phosphate changed by these compounds. 7. It is concluded that the ethanol-induced increase in hepatic phosphatidate phosphohydrolase may at least in part be mediated by the hepatic concentration of metabolites, probably by the concentration of sn-glycerol 3-phosphate."}
{"id": "PMID:218557", "title": "Calcium ions and the regulation of NAD+-linked isocitrate dehydrogenase from the mitochondria of rat heart and other tissues.", "content": "The effects of Ca2+ on the activity of isocitrate dehydrogenase (NAD+) in extracts of rat heart mitochondria were explored in the presence of MgCl2 by using EGTA buffers. In the absence of ADP, Ca2+ (about 30 micrometer) resulted in a slight increase in apparent Km for threo-Ds-isocitrate; in the presence of ADP, Ca2+ (about 25 micrometer) greatly lowered the apparent Km for threo-Ds-isocitrate from 227 micrometer to 53 micrometer without changing the maximum velocity. At 100 micrometer-threo-Ds-isocitrate and 1 mM-ADP, there was an 8-fold activation by Ca2+, with a Km for Ca2+ of 1.2 micrometer. This activation was also observed with Sr2+ (Km 3.1 micrometer), but not with Mn2+ (at concentrations below 2.5 micrometer). Similar effects of Ca2+ were also observed on isocitrate dehydrogenase (NAD+) activity in extracts of mitochondria from liver, kidney, brown adipose tissue and white adipose tissue of the rat. The possible regulatory role of changes in the intramitochondrial concentration of Ca2+ is discussed.", "contents": "Calcium ions and the regulation of NAD+-linked isocitrate dehydrogenase from the mitochondria of rat heart and other tissues. The effects of Ca2+ on the activity of isocitrate dehydrogenase (NAD+) in extracts of rat heart mitochondria were explored in the presence of MgCl2 by using EGTA buffers. In the absence of ADP, Ca2+ (about 30 micrometer) resulted in a slight increase in apparent Km for threo-Ds-isocitrate; in the presence of ADP, Ca2+ (about 25 micrometer) greatly lowered the apparent Km for threo-Ds-isocitrate from 227 micrometer to 53 micrometer without changing the maximum velocity. At 100 micrometer-threo-Ds-isocitrate and 1 mM-ADP, there was an 8-fold activation by Ca2+, with a Km for Ca2+ of 1.2 micrometer. This activation was also observed with Sr2+ (Km 3.1 micrometer), but not with Mn2+ (at concentrations below 2.5 micrometer). Similar effects of Ca2+ were also observed on isocitrate dehydrogenase (NAD+) activity in extracts of mitochondria from liver, kidney, brown adipose tissue and white adipose tissue of the rat. The possible regulatory role of changes in the intramitochondrial concentration of Ca2+ is discussed."}
{"id": "PMID:218558", "title": "Relative rates of turnover of subunits of mitochondrial proteins.", "content": "1. The double-isotope concept [Arias, Doyle & Schimke (1969) J. Biol. Chem. 244, 3303--3315] for the measurement of protein turnover was used to estimate the turnover rates of protein subunits from rat liver submitochondrial fractions resolved by means of polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate. NaH14CO3 and [5-3H]arginine were used as first and second precursors respectively. 2. Marked heterogeneity of protein subunit turnover rates is seen for protein subunits from water-soluble, salt-soluble and Tween 20-soluble mitochondrial proteins. 3. Much lower heterogeneity is seen in the turnover of protein subunits in Triton X-100-soluble material not binding to DEAE-cellulose at low ionic strength. The relative rates of turnover of proteins in this fraction are lower than for proteins in any other submitochondrial fraction. This fraction contains the integral membrane proteins. 4. Incorporation of [3H]arginine into subunits of the cytochrome oxidase complex is greatest for subunits with molecular weights in excess of 20000. 5. No correlation is seen between protein subunit size and the rate of turnover of the protein subunits in any of the submitochondrial fractions.", "contents": "Relative rates of turnover of subunits of mitochondrial proteins. 1. The double-isotope concept [Arias, Doyle & Schimke (1969) J. Biol. Chem. 244, 3303--3315] for the measurement of protein turnover was used to estimate the turnover rates of protein subunits from rat liver submitochondrial fractions resolved by means of polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate. NaH14CO3 and [5-3H]arginine were used as first and second precursors respectively. 2. Marked heterogeneity of protein subunit turnover rates is seen for protein subunits from water-soluble, salt-soluble and Tween 20-soluble mitochondrial proteins. 3. Much lower heterogeneity is seen in the turnover of protein subunits in Triton X-100-soluble material not binding to DEAE-cellulose at low ionic strength. The relative rates of turnover of proteins in this fraction are lower than for proteins in any other submitochondrial fraction. This fraction contains the integral membrane proteins. 4. Incorporation of [3H]arginine into subunits of the cytochrome oxidase complex is greatest for subunits with molecular weights in excess of 20000. 5. No correlation is seen between protein subunit size and the rate of turnover of the protein subunits in any of the submitochondrial fractions."}
{"id": "PMID:218559", "title": "Requirement for negatively charged dispersions of phospholipids for interaction with lipid-depleted adenosine triphosphatase.", "content": "The basis of the requirement for a net negative charge on phospholipid dispersions able to re-activate lipid-depleted (Na++K+)-dependent adenosine triphosphatase was studied. The origin and density of the charge in phospholipid dispersions were varied before interaction with the adenosine triphosphatase protein, and the charge density on restored phospholipid-adenosine triphosphatase complexes was changed after interaction. The results indicated that: (a) re-activation requires a lamellar arrangement of the lipid molecules with sufficient density of negative charge, but not necessarily negatively charged phospholipid molecules; (b) the net charge appears to be necessary for the correct interaction between the enzyme protein and the phospholipids, although the amount of phospholipid that binds to the protein is also a function of the nature of the acyl chains; (c) it is not possible on the basis of these findings and those in the literature to decide unequivocally if the charge is also required for the enzyme reaction itself. The possible relevance of the findings to the situation in vivo is discussed in terms of the charge being concerned only with lipid-protein interaction.", "contents": "Requirement for negatively charged dispersions of phospholipids for interaction with lipid-depleted adenosine triphosphatase. The basis of the requirement for a net negative charge on phospholipid dispersions able to re-activate lipid-depleted (Na++K+)-dependent adenosine triphosphatase was studied. The origin and density of the charge in phospholipid dispersions were varied before interaction with the adenosine triphosphatase protein, and the charge density on restored phospholipid-adenosine triphosphatase complexes was changed after interaction. The results indicated that: (a) re-activation requires a lamellar arrangement of the lipid molecules with sufficient density of negative charge, but not necessarily negatively charged phospholipid molecules; (b) the net charge appears to be necessary for the correct interaction between the enzyme protein and the phospholipids, although the amount of phospholipid that binds to the protein is also a function of the nature of the acyl chains; (c) it is not possible on the basis of these findings and those in the literature to decide unequivocally if the charge is also required for the enzyme reaction itself. The possible relevance of the findings to the situation in vivo is discussed in terms of the charge being concerned only with lipid-protein interaction."}
{"id": "PMID:218560", "title": "Properties of cupric ions in benzylamine oxidase from pig plasma as studied by magnetic-resonance and kinetic methods.", "content": "Benzylamine oxidase from pig plasma has been studied by a variety of chemical and physical techniques. 1. Analytical ultracentrifugation, gel electrophoresis and isoelectric-focusing studies suggest that the enzyme is composed of two subunits with closely similar primary structures. 2. E.s.r. and n.m.r. measurements show that the enzyme contains two well-separated (greater than 0.6 nm) Cu2+ ions at chemically distinct sites. Each Cu2+ ion is coordinated by two water molecules, one 'axial' and the other 'equatorial'. Both water molecules undergo fast exchange (10(5)--10(8) s-1) with solvent and are deprotonated in the pH range 8--9, but only the equatorial water molecule is displaced by the inhibitors N3- and CN-. 3. Kinetic and e.s.r. measurements show that azide and cyanide compete against O2 binding and also make the two Cu2+ sites identical. It is concluded that Cu2+ must participate in the re-oxidation of reduced enzyme by molecular O2.", "contents": "Properties of cupric ions in benzylamine oxidase from pig plasma as studied by magnetic-resonance and kinetic methods. Benzylamine oxidase from pig plasma has been studied by a variety of chemical and physical techniques. 1. Analytical ultracentrifugation, gel electrophoresis and isoelectric-focusing studies suggest that the enzyme is composed of two subunits with closely similar primary structures. 2. E.s.r. and n.m.r. measurements show that the enzyme contains two well-separated (greater than 0.6 nm) Cu2+ ions at chemically distinct sites. Each Cu2+ ion is coordinated by two water molecules, one 'axial' and the other 'equatorial'. Both water molecules undergo fast exchange (10(5)--10(8) s-1) with solvent and are deprotonated in the pH range 8--9, but only the equatorial water molecule is displaced by the inhibitors N3- and CN-. 3. Kinetic and e.s.r. measurements show that azide and cyanide compete against O2 binding and also make the two Cu2+ sites identical. It is concluded that Cu2+ must participate in the re-oxidation of reduced enzyme by molecular O2."}
{"id": "PMID:218561", "title": "Some magnetic properties of Pseudomonas cytochrome oxidase.", "content": "The magnetic properties of the haem groups of Pseudomonas cytochrome oxidase and its cyanide-bound derivatives were studied in both the oxidized and reduced states by means of m.c.d. (magnetic circular dichroism) at low temperatures. In addition, the oxidized forms of the enzyme were also investigated by e.p.r. (electron-paramagnetic-resonance) spectroscopy, and a parallel study, using both e.p.r. and m.c.d., was made on Pseudomonas cytochrome c-551 to aid spectral assignments. For ascorbate-reduced Pseudomonas cytochrome oxidase, the temperature-independence of those features in the m.c.d. spectrum corresponding to the haem c, and the temperature-dependence of those signals corresponding to the haem d1, showed the former to be low-spin and the latter to be high-spin (s = 2). However, addition of cyanide to the reduced enzyme gave a form of the protein that was completely low-spin. The e.p.r. and m.c.d. sectra of oxidized Pseudomonas cytochrome oxidase and its cyanide derivative were consistent with the haem c and d1 components being low-spin in both cases. Pseudomonas cytochrome c-551 was found to be low-spin in both its oxidized and reduced redox states.", "contents": "Some magnetic properties of Pseudomonas cytochrome oxidase. The magnetic properties of the haem groups of Pseudomonas cytochrome oxidase and its cyanide-bound derivatives were studied in both the oxidized and reduced states by means of m.c.d. (magnetic circular dichroism) at low temperatures. In addition, the oxidized forms of the enzyme were also investigated by e.p.r. (electron-paramagnetic-resonance) spectroscopy, and a parallel study, using both e.p.r. and m.c.d., was made on Pseudomonas cytochrome c-551 to aid spectral assignments. For ascorbate-reduced Pseudomonas cytochrome oxidase, the temperature-independence of those features in the m.c.d. spectrum corresponding to the haem c, and the temperature-dependence of those signals corresponding to the haem d1, showed the former to be low-spin and the latter to be high-spin (s = 2). However, addition of cyanide to the reduced enzyme gave a form of the protein that was completely low-spin. The e.p.r. and m.c.d. sectra of oxidized Pseudomonas cytochrome oxidase and its cyanide derivative were consistent with the haem c and d1 components being low-spin in both cases. Pseudomonas cytochrome c-551 was found to be low-spin in both its oxidized and reduced redox states."}
{"id": "PMID:218562", "title": "The mechanism of action of xanthine oxidase. The relationship between the rapid and very rapid molybdenum electron-paramagnetic-resonance signals.", "content": "On the basis of the work of Gutteridge, Tanner & Bray [Biochem. J. (1978) 175, 887-897] and of other data in the literature, a mechanism for the reaction of xanthine oxidase with reducing substrates is proposed. In the Michaelis complex, xanthine is bound to molybdenum via the N-9 nitrogen atom. Coupled transfer of two electrons to molybdenum and the C-8 proton to the enzyme yields (Enzyme)-Mo-SH. Concerted with this process, reaction of the xanthine residue with a nucleophile in the active centre yields a covalent intermediate that breaks down to give the product by alternative pathways at high and at low pH values.", "contents": "The mechanism of action of xanthine oxidase. The relationship between the rapid and very rapid molybdenum electron-paramagnetic-resonance signals. On the basis of the work of Gutteridge, Tanner & Bray [Biochem. J. (1978) 175, 887-897] and of other data in the literature, a mechanism for the reaction of xanthine oxidase with reducing substrates is proposed. In the Michaelis complex, xanthine is bound to molybdenum via the N-9 nitrogen atom. Coupled transfer of two electrons to molybdenum and the C-8 proton to the enzyme yields (Enzyme)-Mo-SH. Concerted with this process, reaction of the xanthine residue with a nucleophile in the active centre yields a covalent intermediate that breaks down to give the product by alternative pathways at high and at low pH values."}
{"id": "PMID:218563", "title": "6 beta-Bromopenicillanic acid inactivates beta-lactamase I.", "content": "The inactivation of beta-lactamase I by preparations of 6alpha-bromopenicillanic acid showed unexpected kinetic features that indicated that the active species was the 6beta-epimer. Samples containing 6beta-bromopenicillanic acid have been synthesized and shown to inactivate the enzyme in a rapid stoicheiometric reaction.", "contents": "6 beta-Bromopenicillanic acid inactivates beta-lactamase I. The inactivation of beta-lactamase I by preparations of 6alpha-bromopenicillanic acid showed unexpected kinetic features that indicated that the active species was the 6beta-epimer. Samples containing 6beta-bromopenicillanic acid have been synthesized and shown to inactivate the enzyme in a rapid stoicheiometric reaction."}
{"id": "PMID:218564", "title": "The preparation of stable enzyme-coenzyme complexes with endogenous catalytic activity.", "content": "N6-(6-Aminohexylcarbamoylmethyl)-NAD+ was coupled to lactate dehydrogenase by using glutaraldehyde to form an active complex. The stability of this complex could be considerably improved by reduction with KBH4, although this treatment caused a partial decrease in specific activity. NAD+ was also coupled directly to the enzyme by this method. All of these complexes exhibited an intrinsic activity in the absence of exogenous NAD+.", "contents": "The preparation of stable enzyme-coenzyme complexes with endogenous catalytic activity. N6-(6-Aminohexylcarbamoylmethyl)-NAD+ was coupled to lactate dehydrogenase by using glutaraldehyde to form an active complex. The stability of this complex could be considerably improved by reduction with KBH4, although this treatment caused a partial decrease in specific activity. NAD+ was also coupled directly to the enzyme by this method. All of these complexes exhibited an intrinsic activity in the absence of exogenous NAD+."}
{"id": "PMID:218595", "title": "HLA-D locus typing in ankylosing spondylitis and Reiter's syndrome.", "content": "HLA-D typing of 44 patients with ankylosing spondylitis (AS) and 31 patients with Reiter's syndrome (RS) did not show increased frequency of any particular Dw allele in either population of patients as compared to controls. Such studies also allowed each patient's general response to be compared with other general responses within each experiment. Contrary to reports of diminished lymphocyte responses in AS patients, hyperresponsiveness in both AS and RS patients was found.", "contents": "HLA-D locus typing in ankylosing spondylitis and Reiter's syndrome. HLA-D typing of 44 patients with ankylosing spondylitis (AS) and 31 patients with Reiter's syndrome (RS) did not show increased frequency of any particular Dw allele in either population of patients as compared to controls. Such studies also allowed each patient's general response to be compared with other general responses within each experiment. Contrary to reports of diminished lymphocyte responses in AS patients, hyperresponsiveness in both AS and RS patients was found."}
{"id": "PMID:218596", "title": "Induction of myeloperoxidase deficiency in granulocytes in lead-intoxicated dogs.", "content": "Lead interferes with heme synthesis in erythrocytes and has a deleterious effect on red cell membranes. We measured myeloperoxidase (MPO) enzyme activity in the granulocytes of dogs fed increasing quantities of lead. Concurrently, iodination capability and in vitro bactericidal activity were measured. Blood lead levels were monitored. Three of 4 dogs poisoned with lead developed significant decreases in MPO enzyme activity in their granulocytes. The decline in MPO activity correlated with cumulative lead toxicity as judged by blood lead levels and clinical signs of lead poisoning. Iodination ability in all 4 dogs decreased with cumulative lead toxicity. After discontinuation of lead administration, recovery of granulocyte MPO activity preceded recovery of iodination ability. This observation suggests the possibility of separate effects of lead on iodination ability and MPO activity. Moderate impairment of bactericidal capacity developed in 3 of 4 dogs with severe lead poisoning. Clinical infections were not observed during the course of the study.", "contents": "Induction of myeloperoxidase deficiency in granulocytes in lead-intoxicated dogs. Lead interferes with heme synthesis in erythrocytes and has a deleterious effect on red cell membranes. We measured myeloperoxidase (MPO) enzyme activity in the granulocytes of dogs fed increasing quantities of lead. Concurrently, iodination capability and in vitro bactericidal activity were measured. Blood lead levels were monitored. Three of 4 dogs poisoned with lead developed significant decreases in MPO enzyme activity in their granulocytes. The decline in MPO activity correlated with cumulative lead toxicity as judged by blood lead levels and clinical signs of lead poisoning. Iodination ability in all 4 dogs decreased with cumulative lead toxicity. After discontinuation of lead administration, recovery of granulocyte MPO activity preceded recovery of iodination ability. This observation suggests the possibility of separate effects of lead on iodination ability and MPO activity. Moderate impairment of bactericidal capacity developed in 3 of 4 dogs with severe lead poisoning. Clinical infections were not observed during the course of the study."}
{"id": "PMID:218602", "title": "Alterations in the expression of the cytomegalovirus-induced cytopathogenic effect in fibroblasts by aflatoxin B1.", "content": "Aflatoxin B1 has been shown both to promote and to alter the expression of the cytopathogenic effect observed when human fibroblasts are challenged with human cytomegalovirus (CMV). Although the cells become round, as is the characteristic effect of this virus on fibroblasts, multinucleate cells are seen to arise from cell fusion within 48 h after virus addition.", "contents": "Alterations in the expression of the cytomegalovirus-induced cytopathogenic effect in fibroblasts by aflatoxin B1. Aflatoxin B1 has been shown both to promote and to alter the expression of the cytopathogenic effect observed when human fibroblasts are challenged with human cytomegalovirus (CMV). Although the cells become round, as is the characteristic effect of this virus on fibroblasts, multinucleate cells are seen to arise from cell fusion within 48 h after virus addition."}
{"id": "PMID:218598", "title": "[Association on Sturge Weber and Klippel Trenaunay Weber syndromes. Apropos of 2 cases].", "content": "The present paper describes two patients with Sturge-Weber and Klippel Tr\u00e9naunay-Weber syndromes. Some etiopathogenic factors are analyzed. We suggest that the association of both diseases in the same patient may be due to a single autosomal dominant gene.", "contents": "[Association on Sturge Weber and Klippel Trenaunay Weber syndromes. Apropos of 2 cases]. The present paper describes two patients with Sturge-Weber and Klippel Tr\u00e9naunay-Weber syndromes. Some etiopathogenic factors are analyzed. We suggest that the association of both diseases in the same patient may be due to a single autosomal dominant gene."}
{"id": "PMID:218603", "title": "Microcylinders of endoplasmic reticulum in histiocytes in patients suffering from Degos' syndrome and dermatomyositis.", "content": "Rare intracytoplasmic membranous inclusions derived from the endoplasmic reticulum were observed in the histiocytes of one case of Dego' syndrome and one case of dermatomyositis. Cross-section and longitudinal sections made it possible to establish a three-dimensional model in which both microcylinders and layers of rolled-up double membranes appear.", "contents": "Microcylinders of endoplasmic reticulum in histiocytes in patients suffering from Degos' syndrome and dermatomyositis. Rare intracytoplasmic membranous inclusions derived from the endoplasmic reticulum were observed in the histiocytes of one case of Dego' syndrome and one case of dermatomyositis. Cross-section and longitudinal sections made it possible to establish a three-dimensional model in which both microcylinders and layers of rolled-up double membranes appear."}
{"id": "PMID:218604", "title": "Studies on 2', 3'-cyclic AMP 3'-phosphohydrolase in rabbit skin.", "content": "Previous studies indicated that 2', 3'-cyclic AMP 3'-phosphohydrolase, an enzyme which splits the 3'-phosphate bond of the 2', 3'-cyclic AMP, is primarily confined to nervous tissue. The physiological function of this enzyme is still unknown. In the present study this enzyme was found to be active in various organs of rabbit, i.e. liver, kidney, heart and skin, although to a much lesser extent than in brain and sciatic nerve. The finding of this enzyme in the skin generated further studies to measure the enzyme activity in normal and diseased skin. Chemically induced (surfactant-treated) skin disorder was used as a model for the present study. Topical application of Polysorbate 85 resulted in a two fold increase of the enzyme activity in rabbit skin. The results suggest that this enzyme may have some role in the repair mechanisms, particularly in the regeneration of damaged membranes.", "contents": "Studies on 2', 3'-cyclic AMP 3'-phosphohydrolase in rabbit skin. Previous studies indicated that 2', 3'-cyclic AMP 3'-phosphohydrolase, an enzyme which splits the 3'-phosphate bond of the 2', 3'-cyclic AMP, is primarily confined to nervous tissue. The physiological function of this enzyme is still unknown. In the present study this enzyme was found to be active in various organs of rabbit, i.e. liver, kidney, heart and skin, although to a much lesser extent than in brain and sciatic nerve. The finding of this enzyme in the skin generated further studies to measure the enzyme activity in normal and diseased skin. Chemically induced (surfactant-treated) skin disorder was used as a model for the present study. Topical application of Polysorbate 85 resulted in a two fold increase of the enzyme activity in rabbit skin. The results suggest that this enzyme may have some role in the repair mechanisms, particularly in the regeneration of damaged membranes."}
{"id": "PMID:218605", "title": "The 2', 3'-cyclic AMP 3'-phosphohydrolase in normal and psoriatic epidermis.", "content": "The activity of the enzyme 2', 3'-cyclic AMP 3'-phosphohydrolase is significantly greater in the 'involved' psoriatic skin than in the 'uninvolved' psoriatic skin or in skin samples taken from persons having clinically normal skin. Although the physiological function of this enzyme is not established, it is possible that, besides being associated with myelin, it may also play some role in cell proliferation and maturation, probably at the membrane level.", "contents": "The 2', 3'-cyclic AMP 3'-phosphohydrolase in normal and psoriatic epidermis. The activity of the enzyme 2', 3'-cyclic AMP 3'-phosphohydrolase is significantly greater in the 'involved' psoriatic skin than in the 'uninvolved' psoriatic skin or in skin samples taken from persons having clinically normal skin. Although the physiological function of this enzyme is not established, it is possible that, besides being associated with myelin, it may also play some role in cell proliferation and maturation, probably at the membrane level."}
{"id": "PMID:218606", "title": "Ethanol inhibition of rabbit reticulocyte haem synthesis at the level of delta-aminolaevulinic acid synthetase.", "content": "Ethanol inhibition of rabbit reticulocyte synthesis occurs as a result of a decrease in haem synthesis. The present study therefore was undertaken in order to localize the inhibitory site of ethanol on the haem biosynthetic pathway. Ethanol (0.05--0.15 M) inhibition of reticulocyte protein synthesis was prevented by simultaneous incubation with 0.025--1 mM delta-aminolaevulinic acid (ALA). Ethanol inhibited both 14C-glycine and 14C-ALA incorporation into haem. However, the extent of haem formation with 14C-ALA as substrate in the presence of ethanol was still equal to that when 14C-glycine was used. These data suggest that ethanol inhibits the haem synthetic pathway at several loci, but that the decrease in haem synthesis, responsible for the decrease in protein synthesis, is due to the inhibition at the rate-limiting enzyme, delta-aminolaevulinic acid synthetase (ALA-S). To confirm this, ALA-S activity was then directly measured in intact reticulocytes, and it was shown that ethanol indeed inhibited its activity. The inhibition of ALA-S was prevented by 10(-4) M dibutyryl cyclic AMP (db cAMP) or theophylline, agents which elevate intracellular cAMP and which have previously been shown to prevent and reverse ethanol inhibition of haem and protein synthesis. Thus, it appears that cAMP protects against ethanol toxicity by preventing inhibition of ALA-S.", "contents": "Ethanol inhibition of rabbit reticulocyte haem synthesis at the level of delta-aminolaevulinic acid synthetase. Ethanol inhibition of rabbit reticulocyte synthesis occurs as a result of a decrease in haem synthesis. The present study therefore was undertaken in order to localize the inhibitory site of ethanol on the haem biosynthetic pathway. Ethanol (0.05--0.15 M) inhibition of reticulocyte protein synthesis was prevented by simultaneous incubation with 0.025--1 mM delta-aminolaevulinic acid (ALA). Ethanol inhibited both 14C-glycine and 14C-ALA incorporation into haem. However, the extent of haem formation with 14C-ALA as substrate in the presence of ethanol was still equal to that when 14C-glycine was used. These data suggest that ethanol inhibits the haem synthetic pathway at several loci, but that the decrease in haem synthesis, responsible for the decrease in protein synthesis, is due to the inhibition at the rate-limiting enzyme, delta-aminolaevulinic acid synthetase (ALA-S). To confirm this, ALA-S activity was then directly measured in intact reticulocytes, and it was shown that ethanol indeed inhibited its activity. The inhibition of ALA-S was prevented by 10(-4) M dibutyryl cyclic AMP (db cAMP) or theophylline, agents which elevate intracellular cAMP and which have previously been shown to prevent and reverse ethanol inhibition of haem and protein synthesis. Thus, it appears that cAMP protects against ethanol toxicity by preventing inhibition of ALA-S."}
{"id": "PMID:218607", "title": "Thromboplastic and fibrinolytic activity of hydatidiform molar tissue and vesicular fluid.", "content": "We found similar levels of thromboplastic activity in molar tissue, vesicular fluid and normal placental tissue from pregnancies matched for gestational age. The fibrinolytic activity of molar tissue and vesicular fluid was, however, increased and vaginal haemorrhage tended to be heavier when fibrinolytic activity was high (p = 0.06). Subsequent choriocarcinoma occurred more frequently in patients with molar tissue which had low fibrinolytic activity (p = 0.08).", "contents": "Thromboplastic and fibrinolytic activity of hydatidiform molar tissue and vesicular fluid. We found similar levels of thromboplastic activity in molar tissue, vesicular fluid and normal placental tissue from pregnancies matched for gestational age. The fibrinolytic activity of molar tissue and vesicular fluid was, however, increased and vaginal haemorrhage tended to be heavier when fibrinolytic activity was high (p = 0.06). Subsequent choriocarcinoma occurred more frequently in patients with molar tissue which had low fibrinolytic activity (p = 0.08)."}
{"id": "PMID:218608", "title": "Ankyloblepharon filiforme adnatum.", "content": "Two cases of ankyloblepharon filiforme adnatum in siblings are presented. One sib had associated cleft lip and palate, the other had bilateral syndactyly of the second and third toes. Father, paternal grandmother, and great-grandmother all had bilateral syndactyly of the second and third toes. Cases of ankyloblepharon filiforme adnatum reported in the ophthalmic literature are reviewed as are cases of ankyloblepharon occurring as part of the popliteal pterygium syndrome. It is postulated that the association of ankyloblepharon with other abnormalities may be part of the spectrum of the popliteal pterygium syndrome with autosomal dominant inheritance, incomplete penetrance, and variable expressivity.", "contents": "Ankyloblepharon filiforme adnatum. Two cases of ankyloblepharon filiforme adnatum in siblings are presented. One sib had associated cleft lip and palate, the other had bilateral syndactyly of the second and third toes. Father, paternal grandmother, and great-grandmother all had bilateral syndactyly of the second and third toes. Cases of ankyloblepharon filiforme adnatum reported in the ophthalmic literature are reviewed as are cases of ankyloblepharon occurring as part of the popliteal pterygium syndrome. It is postulated that the association of ankyloblepharon with other abnormalities may be part of the spectrum of the popliteal pterygium syndrome with autosomal dominant inheritance, incomplete penetrance, and variable expressivity."}
{"id": "PMID:218609", "title": "Isolation and identification of previtamin D3 from the skin of rats exposed to ultraviolet irradiation.", "content": "The process of the photolytic activation of vitamin D precursor(s) in the skin has been elucidated by a detailed analysis of the products formed after ultraviolet light exposure. The photolytic product isolated from the skin of rats exposed to ultraviolet irradiation was identified as previtamin D3 by several criteria including its (a) characteristic ultraviolet absorption spectrum, (b) mass spectrum, and (c) thermal isomerization to vitamin D3, which itself was identified also by mass spectroscopy. Vitamin D3 per se was not formed by ultraviolet irradiation--vitamin D3 arises exclusively from the thermal conversion of previtamin D3. Detectable amounts of lumisterol3 or tachysterol3 were not seen.", "contents": "Isolation and identification of previtamin D3 from the skin of rats exposed to ultraviolet irradiation. The process of the photolytic activation of vitamin D precursor(s) in the skin has been elucidated by a detailed analysis of the products formed after ultraviolet light exposure. The photolytic product isolated from the skin of rats exposed to ultraviolet irradiation was identified as previtamin D3 by several criteria including its (a) characteristic ultraviolet absorption spectrum, (b) mass spectrum, and (c) thermal isomerization to vitamin D3, which itself was identified also by mass spectroscopy. Vitamin D3 per se was not formed by ultraviolet irradiation--vitamin D3 arises exclusively from the thermal conversion of previtamin D3. Detectable amounts of lumisterol3 or tachysterol3 were not seen."}
{"id": "PMID:218611", "title": "Apoproteins of avian very low density lipoprotein: demonstration of a single high molecular weight apoprotein.", "content": "The high molecular weight apoproteins of very low density lipoprotein (VLDL) were compared after preparation of VLDL from plasma and sera of diethylstilbestrol-treated roosters. When prepared from plasma with adequate control of endogenous proteolytic activity, VLDL contained a single high molecular weight apoprotein (apo-VLDL-B) as judged by electrophoresis in polyacrylamide gels containing sodium dodecyl sulfate. Serum VLDL contained multiple apoprotein species, the largest of which corresponded to apo-VLDL-B. Immunological analyses showed that the multiple apoproteins of serum VLDL were quantitatively and qualitatively indistinguishable from plasma apo-VLDL-B. These data indicate that apo-VLDL-B can be cleaved during VLDL isolation to produce an apparent heterogeneity of high molecular weight apoproteins. The molecular weight of plasma apo-VLDL-B was estimated to be 350 000. This protein was stable to reduction and S-carboxymethylation and showed no association with apo-VLDL-II [Chan, L., Jackson, R.L., O'Malley, B. W., & Means, A.R. (1976) J. Clin. Invest. 58, 368] through disulfide linkage. Apo-VLDL-B and apo-VLDL-II represented 54% and 46%, respectively, of the total VLDL protein recovered following gel filtration chromatography in sodium dodecyl sulfate. Protein recovery in the chromatographic analyses (92%) was sufficient to conclude that apo-VLDL-B and apo-VLDL-II are the major and possibly the only apoproteins of chicken VLDL. The molar ratio of the apo-VLDL-II monomer to apo-VLDL-B was estimated to be 32.", "contents": "Apoproteins of avian very low density lipoprotein: demonstration of a single high molecular weight apoprotein. The high molecular weight apoproteins of very low density lipoprotein (VLDL) were compared after preparation of VLDL from plasma and sera of diethylstilbestrol-treated roosters. When prepared from plasma with adequate control of endogenous proteolytic activity, VLDL contained a single high molecular weight apoprotein (apo-VLDL-B) as judged by electrophoresis in polyacrylamide gels containing sodium dodecyl sulfate. Serum VLDL contained multiple apoprotein species, the largest of which corresponded to apo-VLDL-B. Immunological analyses showed that the multiple apoproteins of serum VLDL were quantitatively and qualitatively indistinguishable from plasma apo-VLDL-B. These data indicate that apo-VLDL-B can be cleaved during VLDL isolation to produce an apparent heterogeneity of high molecular weight apoproteins. The molecular weight of plasma apo-VLDL-B was estimated to be 350 000. This protein was stable to reduction and S-carboxymethylation and showed no association with apo-VLDL-II [Chan, L., Jackson, R.L., O'Malley, B. W., & Means, A.R. (1976) J. Clin. Invest. 58, 368] through disulfide linkage. Apo-VLDL-B and apo-VLDL-II represented 54% and 46%, respectively, of the total VLDL protein recovered following gel filtration chromatography in sodium dodecyl sulfate. Protein recovery in the chromatographic analyses (92%) was sufficient to conclude that apo-VLDL-B and apo-VLDL-II are the major and possibly the only apoproteins of chicken VLDL. The molar ratio of the apo-VLDL-II monomer to apo-VLDL-B was estimated to be 32."}
{"id": "PMID:218614", "title": "Phospholipid composition of substrate adhesion sites of normal, virus-transformed, and revertant murine cells.", "content": "The phospholipid composition of cell-substratum adhesion sites, obtained after EGTA-mediated detachment of cells from the tissue-culture substratum, was determined for [32P]orthophosphate radiolabeled Balb/c 3T3, SV40-transformed (SVT2), and concanavalin A selected revertant variant cell lines. All of the major phospholipid classes were found in the substrate-attached material, but there was an enrichment for specific phospholipid species in this adhesive material as compared to whole-cell and surface-enriched membranes. The phospholipid composition was remarkable similar for the whole-cell and surface-enriched membrane fractions from the three cell lines. However, pronounced differences in the phospholipid composition of the adhesion sites were observed as a result of viral transformation--SVT2 sites were clearly enriched in phosphatidylethanolamine and depleted in phosphatidylcholine when compared to 3T3 sites. This alteration in adhesion site phospholipids of transformed cells reverted to 3T3-like values in the adhesive material of revertant cells. The composition of adhesive material of newly attaching cells was also examined to differentiate compositional differences between \"footpad\" adhesion sites and \"footprints\", adhesive material pinched off from the posterior of cells as they move across the substratum. Pulse and pulse-chase analyses of the [32P]phospholipids revealed some differences in synthesis and turnover rates in the three cell lines; in addition, altered rates of deposition of newly synthesized material into adhesion sites of transformed cells were observed. These data afford further evidence that the cell-substratum adhesion sites are highly specialized areas of the cell surface enriched in components which are intricately involved in the adhesive process. The transformation-dependent changes in adhesion site phospholipids may help to determine the basis for the altered adhesive properties of transformed cells.", "contents": "Phospholipid composition of substrate adhesion sites of normal, virus-transformed, and revertant murine cells. The phospholipid composition of cell-substratum adhesion sites, obtained after EGTA-mediated detachment of cells from the tissue-culture substratum, was determined for [32P]orthophosphate radiolabeled Balb/c 3T3, SV40-transformed (SVT2), and concanavalin A selected revertant variant cell lines. All of the major phospholipid classes were found in the substrate-attached material, but there was an enrichment for specific phospholipid species in this adhesive material as compared to whole-cell and surface-enriched membranes. The phospholipid composition was remarkable similar for the whole-cell and surface-enriched membrane fractions from the three cell lines. However, pronounced differences in the phospholipid composition of the adhesion sites were observed as a result of viral transformation--SVT2 sites were clearly enriched in phosphatidylethanolamine and depleted in phosphatidylcholine when compared to 3T3 sites. This alteration in adhesion site phospholipids of transformed cells reverted to 3T3-like values in the adhesive material of revertant cells. The composition of adhesive material of newly attaching cells was also examined to differentiate compositional differences between \"footpad\" adhesion sites and \"footprints\", adhesive material pinched off from the posterior of cells as they move across the substratum. Pulse and pulse-chase analyses of the [32P]phospholipids revealed some differences in synthesis and turnover rates in the three cell lines; in addition, altered rates of deposition of newly synthesized material into adhesion sites of transformed cells were observed. These data afford further evidence that the cell-substratum adhesion sites are highly specialized areas of the cell surface enriched in components which are intricately involved in the adhesive process. The transformation-dependent changes in adhesion site phospholipids may help to determine the basis for the altered adhesive properties of transformed cells."}
{"id": "PMID:218615", "title": "Carbon-13-enriched carbohydrates: preparation of triose, tetrose, and pentose phosphates.", "content": "Three-, four-, and five-carbon aldononitrile phosphates were prepared, purified, and catalyticlly reduced with palladium--barium sulfate (5%) to the corresponding aldose phosphates in high yields at pH 1.7 +/- 0.1 and atmopsheric pressure. DL-Glyceraldehyde 3-phosphate and the tetrose 4-phosphates were prepared with carbon-13 enrichment at C-1, while the pentose 5-phosphates were prepared with enrichment at C-1 and C-2. Preparations of glycolaldehyde phosphate and d-glyceraldehyde 3-phosphate by lead tetra-acetate oxidation of glycerol phosphate and fructose 6-phosphate, respectively, are described. The proportions of cyclic hemiacetals and linear gem-diol forms of the two- to five-carbon aldose phosphates in aqueous solution are reported. Carbon-13 chemical shifts and carbon--phosphorus and carbon--hydrogen coupling constants for the furanose phosphate ring and linear gem-diol phosphates are reported and discussed. d-[2(-13)C]Ribulose 1,5-bisphosphate and L-[3,4(-13)C]sorbose 1,6-bisphosphate were prepared enzymatically from D-[2(-13)C]ribose 5-phosphate and dl-[1(-13)C]glyceraldehyde 3-phosphate, respectively.", "contents": "Carbon-13-enriched carbohydrates: preparation of triose, tetrose, and pentose phosphates. Three-, four-, and five-carbon aldononitrile phosphates were prepared, purified, and catalyticlly reduced with palladium--barium sulfate (5%) to the corresponding aldose phosphates in high yields at pH 1.7 +/- 0.1 and atmopsheric pressure. DL-Glyceraldehyde 3-phosphate and the tetrose 4-phosphates were prepared with carbon-13 enrichment at C-1, while the pentose 5-phosphates were prepared with enrichment at C-1 and C-2. Preparations of glycolaldehyde phosphate and d-glyceraldehyde 3-phosphate by lead tetra-acetate oxidation of glycerol phosphate and fructose 6-phosphate, respectively, are described. The proportions of cyclic hemiacetals and linear gem-diol forms of the two- to five-carbon aldose phosphates in aqueous solution are reported. Carbon-13 chemical shifts and carbon--phosphorus and carbon--hydrogen coupling constants for the furanose phosphate ring and linear gem-diol phosphates are reported and discussed. d-[2(-13)C]Ribulose 1,5-bisphosphate and L-[3,4(-13)C]sorbose 1,6-bisphosphate were prepared enzymatically from D-[2(-13)C]ribose 5-phosphate and dl-[1(-13)C]glyceraldehyde 3-phosphate, respectively."}
{"id": "PMID:218616", "title": "Structure of lactate dehydrogenase inhibitor generated from coenzyme.", "content": "Two inhibitors of lactate dehydrogenase generated during NADH storage have been isolated by chromatography. One is a dimer of the dinucleotide where the AMP moiety is unmodified. The other is also generated from NAD+ in the presence of a high concentration of phosphate ions at alkaline pH. This inhibitor was proved to be the addition compound of one phosphate group to position C-4 of the nicotinamide ring of NAD+ by NMR spectroscopy, enzymatic cleavage, and dissociation to NAD+ at neutral pH. This compound is a competitive inhibitor with respect to NAD+ in the presence of the lactate dehydrogenase with a Ki of 2 X 10(-7) M. The interaction of this inhibitor with lactate dehydrogenase is discussed relative to the structure of this enzyme.", "contents": "Structure of lactate dehydrogenase inhibitor generated from coenzyme. Two inhibitors of lactate dehydrogenase generated during NADH storage have been isolated by chromatography. One is a dimer of the dinucleotide where the AMP moiety is unmodified. The other is also generated from NAD+ in the presence of a high concentration of phosphate ions at alkaline pH. This inhibitor was proved to be the addition compound of one phosphate group to position C-4 of the nicotinamide ring of NAD+ by NMR spectroscopy, enzymatic cleavage, and dissociation to NAD+ at neutral pH. This compound is a competitive inhibitor with respect to NAD+ in the presence of the lactate dehydrogenase with a Ki of 2 X 10(-7) M. The interaction of this inhibitor with lactate dehydrogenase is discussed relative to the structure of this enzyme."}
{"id": "PMID:218619", "title": "Labeling of cytochrome c oxidase with [35S]diazobenzenesulfonate. Orientation of this electron transfer complex in the inner mitochondrial membrane.", "content": "Isolated cytochrome c oxidase was fractionated by native-gel electrophoresis in Triton X-100, and a preparation of enzyme almost completely free of the usual impurities was recovered. This fraction was used to generate antibodies specific to cytochrome c oxidase. These antibodies inhibited cytochrome c oxidase activity rapidly and completely and immunoprecipitated an enzyme containing seven different subunits from detergent-solubilized mitochondria or submitochondrial particles. Reaction of detergent-solubilized cytochrome c oxidase with [35S]diazobenzenesulfonate labeled all seven subunits although I and VI were much less reactive than the other five components. When cytochrome c oxidase was immunoprecipitated from mitochondria which had been reacted with [35S]DABS, subunits II and III were the only components labeled. When the complex was immunoprecipitated from labeled submitochondrial particles, II, III, IV, V, and VII were all labeled. Polypeptides I and VI were not labeled from either side of the membrane. These results confirm earlier studies which showed that cytochrome c oxidase spans the mitochondrial inner membrane and is asymmetrically arranged across this permeability barrier.", "contents": "Labeling of cytochrome c oxidase with [35S]diazobenzenesulfonate. Orientation of this electron transfer complex in the inner mitochondrial membrane. Isolated cytochrome c oxidase was fractionated by native-gel electrophoresis in Triton X-100, and a preparation of enzyme almost completely free of the usual impurities was recovered. This fraction was used to generate antibodies specific to cytochrome c oxidase. These antibodies inhibited cytochrome c oxidase activity rapidly and completely and immunoprecipitated an enzyme containing seven different subunits from detergent-solubilized mitochondria or submitochondrial particles. Reaction of detergent-solubilized cytochrome c oxidase with [35S]diazobenzenesulfonate labeled all seven subunits although I and VI were much less reactive than the other five components. When cytochrome c oxidase was immunoprecipitated from mitochondria which had been reacted with [35S]DABS, subunits II and III were the only components labeled. When the complex was immunoprecipitated from labeled submitochondrial particles, II, III, IV, V, and VII were all labeled. Polypeptides I and VI were not labeled from either side of the membrane. These results confirm earlier studies which showed that cytochrome c oxidase spans the mitochondrial inner membrane and is asymmetrically arranged across this permeability barrier."}
{"id": "PMID:218620", "title": "Immunochemical analysis of membrane vesicles from Escherichia coli.", "content": "Membrane vesicles isolated from Escherichia coli ML 308--225 have been analyzed by crossed immunoelectrophoresis, and immunoprecipitates corresponding to the following cellular components have been identified: ATPase (EC 3.6.1,3), two or three NADH dehydrogenases (EC 1.6.99.3), D-lactate dehydrogenase (EC 1.1.1.27), glutamate dehydrogenase (EC 1.4.1.4), dihydro-orotate dehydrogenase (EC 1.3.3.1), 6-phosphogluconate dehydrogenase (EC 1.1.1.43), polynucleotide phosphorylase (EC 2.3.7.8), beta-galactosidase (EC 3.2.1.23), lipopolysaccharide, and Braun's lipoprotein. The cellular origin of many of the vesicle immunogens is determined, and Braun's lipoprotein is used as a marker to quantitate the extent of outer membrane contamination (less than 3%). Membrane antigens are also characterized with regard to their amphiphilic or hydrophilic properties by charge-shift crossed immunoelectrophoresis. Furthermore, the following immunogens cross-react with components in membrane vesicles prepared from Salmonella typhimurium: one of the three NADH dehydrogenases, ATPase, polynucleotide phosphorylase, 6-phosphogluconate dehydrogenase, Braun's lipoprotein, and three unidentified antigens. In the accompanying paper [Owen, P., & Kaback, H. R. (1979) Biochemistry 18 (following paper in this issue)] quantitative immunoadsorption is utilized to establish the topology of the vesicles with respect to the distribution of antigens on the inner and outer faces of the membrane.", "contents": "Immunochemical analysis of membrane vesicles from Escherichia coli. Membrane vesicles isolated from Escherichia coli ML 308--225 have been analyzed by crossed immunoelectrophoresis, and immunoprecipitates corresponding to the following cellular components have been identified: ATPase (EC 3.6.1,3), two or three NADH dehydrogenases (EC 1.6.99.3), D-lactate dehydrogenase (EC 1.1.1.27), glutamate dehydrogenase (EC 1.4.1.4), dihydro-orotate dehydrogenase (EC 1.3.3.1), 6-phosphogluconate dehydrogenase (EC 1.1.1.43), polynucleotide phosphorylase (EC 2.3.7.8), beta-galactosidase (EC 3.2.1.23), lipopolysaccharide, and Braun's lipoprotein. The cellular origin of many of the vesicle immunogens is determined, and Braun's lipoprotein is used as a marker to quantitate the extent of outer membrane contamination (less than 3%). Membrane antigens are also characterized with regard to their amphiphilic or hydrophilic properties by charge-shift crossed immunoelectrophoresis. Furthermore, the following immunogens cross-react with components in membrane vesicles prepared from Salmonella typhimurium: one of the three NADH dehydrogenases, ATPase, polynucleotide phosphorylase, 6-phosphogluconate dehydrogenase, Braun's lipoprotein, and three unidentified antigens. In the accompanying paper [Owen, P., & Kaback, H. R. (1979) Biochemistry 18 (following paper in this issue)] quantitative immunoadsorption is utilized to establish the topology of the vesicles with respect to the distribution of antigens on the inner and outer faces of the membrane."}
{"id": "PMID:218621", "title": "Antigenic architecture of membrane vesicles from Escherichia coli.", "content": "The antigenic architecture of membrane vesicles prepared from Escherichia coli ML 308--225 has been studied using crossed immunoelectrophoresis. Progressive immunoadsorption experiments conducted with control vesicles and with physically disrupted vesicles were used to monitor and quantitate the expression of 14 different immunogens. Eleven immunogens, including NADH dehydrogenase (EC 1.6.33.3), D-lactate dehydrogenase (EC 1.1.1.27), dihydro-orotate dehydrogenase (EC 1.3.3.1), 6-phosphogluconate dehydrogenase (EC 1.1.1.43), polynucleotide phosphorylase (EC 2.3.7.8), and beta-galactosidase (EC 3.2.1.23), exhibit minimal expression (10% or less) unless the vesicles are disrupted. Three unidentified antigens are expressed to a similar extent in untreated and disrupted vesicles. Consideration of these and other results [Owen, P., & Kaback, H. R. (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 3148] in terms of membrane polarity, dislocation of antigens, and possible transmembrane orientation of some immunogens reveals that over 95% of the membrane in the vesicle preparations is in the form of sealed sacculi with the same orientation as the intact cell. Furthermore, antigens are distributed across the membrane in a highly asymmetric manner, indicating that dislocation of components from the inner to the outer surface of the membrane during vesicle preparation does not occur to an extent exceeding 10%.", "contents": "Antigenic architecture of membrane vesicles from Escherichia coli. The antigenic architecture of membrane vesicles prepared from Escherichia coli ML 308--225 has been studied using crossed immunoelectrophoresis. Progressive immunoadsorption experiments conducted with control vesicles and with physically disrupted vesicles were used to monitor and quantitate the expression of 14 different immunogens. Eleven immunogens, including NADH dehydrogenase (EC 1.6.33.3), D-lactate dehydrogenase (EC 1.1.1.27), dihydro-orotate dehydrogenase (EC 1.3.3.1), 6-phosphogluconate dehydrogenase (EC 1.1.1.43), polynucleotide phosphorylase (EC 2.3.7.8), and beta-galactosidase (EC 3.2.1.23), exhibit minimal expression (10% or less) unless the vesicles are disrupted. Three unidentified antigens are expressed to a similar extent in untreated and disrupted vesicles. Consideration of these and other results [Owen, P., & Kaback, H. R. (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 3148] in terms of membrane polarity, dislocation of antigens, and possible transmembrane orientation of some immunogens reveals that over 95% of the membrane in the vesicle preparations is in the form of sealed sacculi with the same orientation as the intact cell. Furthermore, antigens are distributed across the membrane in a highly asymmetric manner, indicating that dislocation of components from the inner to the outer surface of the membrane during vesicle preparation does not occur to an extent exceeding 10%."}
{"id": "PMID:218622", "title": "Cross-linking of the cAMP receptor protein of Escherichia coli by o-phenylenedimaleimide as a probe of conformation.", "content": "Reaction of the cAMP (cyclic adenosine 3'--5'-monophosphate) receptor protein (CRP) of Escherichia coli with the bifunctional reagent o-phenylenedimaleimide (oPDM) results in the cross-linking of the two subunits of a CRP protomer. In the presence of cAMP the rate of cross-linking increases. CRP modified with oPDM retains [3H]cAMP binding activity but loses [3H]d(I-C)n binding activity. Proteolysis of cross-linked CRP gives distinct sodium dodecyl sulfate-polyacrylamide gel electrophoretic patterns depending upon whether cAMP was present during the reaction with oPDM. CRP cross-linked in the absence of cAMP retains the same relative resistance to proteolysis as unmodified CRP. The presence of 0.1 mM cAMP during proteolysis results in the production of two fragments, one of approximately 13 000 daltons and a second of approximately 20 000 daltons. CRP cross-linked with oPDM in the presence of cAMP (then dialyzed to remove cAMP) remains sensitive to alpha-chymotrypsin digestion even in the absence of added cAMP producing only the 13 000-dalton fragment. It is suggested that the nature of the oPDM cross-link is a consequence of the conformational state of CRP.", "contents": "Cross-linking of the cAMP receptor protein of Escherichia coli by o-phenylenedimaleimide as a probe of conformation. Reaction of the cAMP (cyclic adenosine 3'--5'-monophosphate) receptor protein (CRP) of Escherichia coli with the bifunctional reagent o-phenylenedimaleimide (oPDM) results in the cross-linking of the two subunits of a CRP protomer. In the presence of cAMP the rate of cross-linking increases. CRP modified with oPDM retains [3H]cAMP binding activity but loses [3H]d(I-C)n binding activity. Proteolysis of cross-linked CRP gives distinct sodium dodecyl sulfate-polyacrylamide gel electrophoretic patterns depending upon whether cAMP was present during the reaction with oPDM. CRP cross-linked in the absence of cAMP retains the same relative resistance to proteolysis as unmodified CRP. The presence of 0.1 mM cAMP during proteolysis results in the production of two fragments, one of approximately 13 000 daltons and a second of approximately 20 000 daltons. CRP cross-linked with oPDM in the presence of cAMP (then dialyzed to remove cAMP) remains sensitive to alpha-chymotrypsin digestion even in the absence of added cAMP producing only the 13 000-dalton fragment. It is suggested that the nature of the oPDM cross-link is a consequence of the conformational state of CRP."}
{"id": "PMID:218623", "title": "Accessibility of adenine binding sites in dehydrogenases to small molecules studied by fluorescence quenching.", "content": "Quenching of the fluorescence of ethenoadenine derivatives by iodide ions and by methionine was studied in solution and when the nucleotides were bound to several dehydrogenases. The fluorescence of epsilonADPR in neutral aqueous solution is dynamically quenched by both quenching agents. The quenching of free epsilonNAD+ by methionine was found to be predominantly static and was satisfactorily described to result from complex formation between quencher and dinucleotide. The rat constant for quenching by iodide of epsilonNAD+ in the ternary complex with LADH and pyrazole is comparable to that of free epsilonADPR or epsilonADP. it is concluded that the bound epsilon-adenine ring is partially exposed to the solvent. The opening, to the solvent, of the adenine binding site is not large enough to allow free methionine diffusion since the rate constant for quenching of bound coenzyme by this quenching agent is relatively small. The difference between the rate constants for quenching of free and enzyme bound nucleotide was used to evaluate the binding constants of epsilonADPR to GPDH, epsilonNAD+ to LDH, and oxalate to the LDH:epsilonNAD+ complex. This technique may prove to be particularly useful when the binding of a fluorescent ligand to a protein is not accompanied by significant changes in its fluorescence.", "contents": "Accessibility of adenine binding sites in dehydrogenases to small molecules studied by fluorescence quenching. Quenching of the fluorescence of ethenoadenine derivatives by iodide ions and by methionine was studied in solution and when the nucleotides were bound to several dehydrogenases. The fluorescence of epsilonADPR in neutral aqueous solution is dynamically quenched by both quenching agents. The quenching of free epsilonNAD+ by methionine was found to be predominantly static and was satisfactorily described to result from complex formation between quencher and dinucleotide. The rat constant for quenching by iodide of epsilonNAD+ in the ternary complex with LADH and pyrazole is comparable to that of free epsilonADPR or epsilonADP. it is concluded that the bound epsilon-adenine ring is partially exposed to the solvent. The opening, to the solvent, of the adenine binding site is not large enough to allow free methionine diffusion since the rate constant for quenching of bound coenzyme by this quenching agent is relatively small. The difference between the rate constants for quenching of free and enzyme bound nucleotide was used to evaluate the binding constants of epsilonADPR to GPDH, epsilonNAD+ to LDH, and oxalate to the LDH:epsilonNAD+ complex. This technique may prove to be particularly useful when the binding of a fluorescent ligand to a protein is not accompanied by significant changes in its fluorescence."}
{"id": "PMID:218625", "title": "Apolipoprotein A-II: chemical synthesis and biophysical properties of three peptides corresponding to fragments in the amino-terminal half.", "content": "Three peptide fragments of apolipoprotein A-II corresponding to residues 17--31, 12--31, and 7--31 have been synthesized by solid-phase techniques and purified to apparent homogeneity. Each of these fragments contains residues 18--30, a region previously proposed to possess potential amphipathic helical properties. Secondary structural changes of these synthetic fragments accompanying their interaction with phospholipid have been studied by circular dichroism. The magnitude of this interaction has been evaluated from the yields and stoichiometry of lipid-protein complexes isolated by density gradient ultracentrifugation. Fragment 17--31, the smallest peptide containing the proposed amphipathic helix, did not interact with dimyristoylphosphatidylcholine (DMPC) single bilayer vesicles at 24 degrees C; upon addition of DMPC, no ellipticity change could be detected nor could a stable lipid-peptide complex be isolated. However, fragments 12--31 and 7--31 did interact with phosphilipid; in the absence of lipid, both fragments had primarily disordered structures, but when isolated as DMPC-peptide complexes, both fragments possessed increased helical structure. The phospholipid:peptide molar ratio was 14:1 for fragment 12--31 and 27:1 for fragment 7--31. Studies of space-filling models of these fragments suggest that hydrophobicity and/or length are important properties of phospholipid binding apoproteins.", "contents": "Apolipoprotein A-II: chemical synthesis and biophysical properties of three peptides corresponding to fragments in the amino-terminal half. Three peptide fragments of apolipoprotein A-II corresponding to residues 17--31, 12--31, and 7--31 have been synthesized by solid-phase techniques and purified to apparent homogeneity. Each of these fragments contains residues 18--30, a region previously proposed to possess potential amphipathic helical properties. Secondary structural changes of these synthetic fragments accompanying their interaction with phospholipid have been studied by circular dichroism. The magnitude of this interaction has been evaluated from the yields and stoichiometry of lipid-protein complexes isolated by density gradient ultracentrifugation. Fragment 17--31, the smallest peptide containing the proposed amphipathic helix, did not interact with dimyristoylphosphatidylcholine (DMPC) single bilayer vesicles at 24 degrees C; upon addition of DMPC, no ellipticity change could be detected nor could a stable lipid-peptide complex be isolated. However, fragments 12--31 and 7--31 did interact with phosphilipid; in the absence of lipid, both fragments had primarily disordered structures, but when isolated as DMPC-peptide complexes, both fragments possessed increased helical structure. The phospholipid:peptide molar ratio was 14:1 for fragment 12--31 and 27:1 for fragment 7--31. Studies of space-filling models of these fragments suggest that hydrophobicity and/or length are important properties of phospholipid binding apoproteins."}
{"id": "PMID:218626", "title": "Isolation of Desulfuromonas acetoxidans cytochrome c-551.5 from the mixed culture 'Chloropseudomonas ethylica'.", "content": "The mixed culture 'Chloropseudomonas ethylica' strain 2K has been grown on a medium which enhanced the yield of cytochrome c-551.5 from Desulfuromonas acetoxidans. The cytochrome was purified to homogeneity and an isoelectric point of 8.40 was determined. A determination of the amide content indicated that the cytochrome contains two more amides than previously reported.", "contents": "Isolation of Desulfuromonas acetoxidans cytochrome c-551.5 from the mixed culture 'Chloropseudomonas ethylica'. The mixed culture 'Chloropseudomonas ethylica' strain 2K has been grown on a medium which enhanced the yield of cytochrome c-551.5 from Desulfuromonas acetoxidans. The cytochrome was purified to homogeneity and an isoelectric point of 8.40 was determined. A determination of the amide content indicated that the cytochrome contains two more amides than previously reported."}
{"id": "PMID:218627", "title": "A temperature-induced absorption band centered in the region of 666 nm related to the configuration of the active site in frozen cytochrome oxidase.", "content": "The existence of a temperature-induced absorption band centred in the region of 666 nm is demonstrated for both membrane-bound and soluble cytochrome oxidase in the frozen state. The 666 nm band is generated solely by an increase in temperature of both fully reduced and mixed valence state cytochrome oxidase in the presence of CO or O2 within the 'pocket' containing the active site; it is not formed in the absence of both CO and O2 from the sample. The formation of the 666 nm band is entirely reversible when the temperature is decreased again and its formation is not dependent on the presence of liganded CO at the sixth coordination site of haem a3 in the low temperature range (below --120 degrees C) prior to photolysis. The shape and intensity of the 666 nm band are not affected by the extent of CO recombination following flash and photolysis and temperature increase and are not affected by changes in the valence states of the four metal centres when the O2 reaction is in progress.", "contents": "A temperature-induced absorption band centered in the region of 666 nm related to the configuration of the active site in frozen cytochrome oxidase. The existence of a temperature-induced absorption band centred in the region of 666 nm is demonstrated for both membrane-bound and soluble cytochrome oxidase in the frozen state. The 666 nm band is generated solely by an increase in temperature of both fully reduced and mixed valence state cytochrome oxidase in the presence of CO or O2 within the 'pocket' containing the active site; it is not formed in the absence of both CO and O2 from the sample. The formation of the 666 nm band is entirely reversible when the temperature is decreased again and its formation is not dependent on the presence of liganded CO at the sixth coordination site of haem a3 in the low temperature range (below --120 degrees C) prior to photolysis. The shape and intensity of the 666 nm band are not affected by the extent of CO recombination following flash and photolysis and temperature increase and are not affected by changes in the valence states of the four metal centres when the O2 reaction is in progress."}
{"id": "PMID:218628", "title": "The kinetic dissection of transport from metabolic trapping during substrate uptake by intact cells. Uridine uptake by quiescent and serum-activated Nil 8 hamster cells and their murine sarcoma virus-transformed counterparts.", "content": "1. We present a theoretical analysis of the tandem processes of transport and metabolic trapping which together constitute uptake of a substrate by intact cells. 2. Transport is assumed to occur by means of a simple carrier here analysed in its general form. Trapping is assumed to occur by a simple enzymic reaction. 3. We show how to obtain the separate parameters of the steps by analysing uptake data over a range of uptake times and substrate concentrations. 4. We present uptake data for uridine and cytosine-beta-D-arabinoside entering Nil 8 hamster fibroblasts, normal and murine sarcoma virus transformed, in the quiescent condition and after stimulation by added serum. We analyse the data in terms of the theory for tandem processes. 5. Transport is characterised by a system having a high Km and a high V for entry. The data for cytosine-beta-D-arabinoside suggest that the cytosine-beta-D-arabinoside system is not far from a symmetric one. The data for uridine transport do not differ when quiescent and serum-activated cells are compared. Transformed cells transport uridine at half the maximum velocity of normal cells, with or without added serum. 6. Trapping of cytosine-beta-D-arabinoside is insignificant. Trapping of uridine occurs by a system with both V and Km at least an order of magnitude smaller than are these parameters for transport. Trapping of uridine by non-transformed cells activated by serum, has twice the V of such cells in the quiescent state. 7. In the virus-transformed cells, the control of uridine trapping by added serum is lost, along with control of growth by this stimulant.", "contents": "The kinetic dissection of transport from metabolic trapping during substrate uptake by intact cells. Uridine uptake by quiescent and serum-activated Nil 8 hamster cells and their murine sarcoma virus-transformed counterparts. 1. We present a theoretical analysis of the tandem processes of transport and metabolic trapping which together constitute uptake of a substrate by intact cells. 2. Transport is assumed to occur by means of a simple carrier here analysed in its general form. Trapping is assumed to occur by a simple enzymic reaction. 3. We show how to obtain the separate parameters of the steps by analysing uptake data over a range of uptake times and substrate concentrations. 4. We present uptake data for uridine and cytosine-beta-D-arabinoside entering Nil 8 hamster fibroblasts, normal and murine sarcoma virus transformed, in the quiescent condition and after stimulation by added serum. We analyse the data in terms of the theory for tandem processes. 5. Transport is characterised by a system having a high Km and a high V for entry. The data for cytosine-beta-D-arabinoside suggest that the cytosine-beta-D-arabinoside system is not far from a symmetric one. The data for uridine transport do not differ when quiescent and serum-activated cells are compared. Transformed cells transport uridine at half the maximum velocity of normal cells, with or without added serum. 6. Trapping of cytosine-beta-D-arabinoside is insignificant. Trapping of uridine occurs by a system with both V and Km at least an order of magnitude smaller than are these parameters for transport. Trapping of uridine by non-transformed cells activated by serum, has twice the V of such cells in the quiescent state. 7. In the virus-transformed cells, the control of uridine trapping by added serum is lost, along with control of growth by this stimulant."}
{"id": "PMID:218629", "title": "An analysis of concanavalin A-mediated agglutination in two Chinese hamster ovary subclones whose surface phenotypes respond to maintenance in medium supplemented with dibutyryl cyclic AMP. V. Biochemical composition of the plasma membrane.", "content": "We have used two Chinese hamster ovary subclones whose surface phenotype has been extensively investigated with regard concanavalin A-mediated cell-cell agglutination and concanavalin A-induced receptor site clustering to investigate what changes in membrane composition, if any, can be correlated with the concanavalin A-detected changes in surface phenotype. These cell clones are uniquely disposed for this purpose since maintenance of the cells under different growth conditions produces changes in agglutinability and receptor site mobility in one cell clone (H-7W) but not the other (K-1). After extensive characterization of the surface membranes of these two subclones we have been unable to identify any change in the membrane peptides, glycopeptide, cholesterol, or fatty acid composition which can be directly correlated with the concanavalin A-detected surface phenotypes. It is of particular interest to note that we have been unable to correlate the presence or absence of the large external transformation-sensitive glycoprotein with the relative mobility of the lectin receptors or with the degree of concanavalin A-mediated cell agglutination. Furthermore we have been unable, in this system, to corroborate earlier data suggesting a role for cholesterol in determining the relative mobility of the lectin receptors. Thus using a cell system consisting of genetically matched cell clones, we have been unable to identify any changes in the biochemical composition of the plasma membrane which might be associated with the surface phenotypes detected by concanavalin A.", "contents": "An analysis of concanavalin A-mediated agglutination in two Chinese hamster ovary subclones whose surface phenotypes respond to maintenance in medium supplemented with dibutyryl cyclic AMP. V. Biochemical composition of the plasma membrane. We have used two Chinese hamster ovary subclones whose surface phenotype has been extensively investigated with regard concanavalin A-mediated cell-cell agglutination and concanavalin A-induced receptor site clustering to investigate what changes in membrane composition, if any, can be correlated with the concanavalin A-detected changes in surface phenotype. These cell clones are uniquely disposed for this purpose since maintenance of the cells under different growth conditions produces changes in agglutinability and receptor site mobility in one cell clone (H-7W) but not the other (K-1). After extensive characterization of the surface membranes of these two subclones we have been unable to identify any change in the membrane peptides, glycopeptide, cholesterol, or fatty acid composition which can be directly correlated with the concanavalin A-detected surface phenotypes. It is of particular interest to note that we have been unable to correlate the presence or absence of the large external transformation-sensitive glycoprotein with the relative mobility of the lectin receptors or with the degree of concanavalin A-mediated cell agglutination. Furthermore we have been unable, in this system, to corroborate earlier data suggesting a role for cholesterol in determining the relative mobility of the lectin receptors. Thus using a cell system consisting of genetically matched cell clones, we have been unable to identify any changes in the biochemical composition of the plasma membrane which might be associated with the surface phenotypes detected by concanavalin A."}
{"id": "PMID:218630", "title": "Studies on the filtration properties of isolated renal basement membranes.", "content": "1. The filtration properties of films of renal basement membrane were studied in vitro using pressure filtration chambers. 2. Retention of cytochrome c by the films was found to be dependent upon the filtration pressure indicating that it was transferred across the films by convective as well as diffusive flow. In contrast, serum albumin was transferred by diffusive movement only. 3. When solutions containing both cytochrome c and IgG were filtered it was found that increasing the filtration pressure reduced the flux of cytochrome c across the films. A similar phenomenon occurred when serum was filtered, less protein passed through the films at high filtration pressures. These phenomena are explained by concentration-polarisation effects. 4. The flux of cytochrome c through the films was found to decrease in a non-linear manner as the films thickness was increased. With thin films, the flux of cytochrome c increased in a non-linear manner as the concentration of the protein in the overstanding solution was increased. With thicker films the flux was linearly dependent on concentration. These findings are interpreted as supporting the view that movement of cytochrome c occurs, at least in part, by convective flow.", "contents": "Studies on the filtration properties of isolated renal basement membranes. 1. The filtration properties of films of renal basement membrane were studied in vitro using pressure filtration chambers. 2. Retention of cytochrome c by the films was found to be dependent upon the filtration pressure indicating that it was transferred across the films by convective as well as diffusive flow. In contrast, serum albumin was transferred by diffusive movement only. 3. When solutions containing both cytochrome c and IgG were filtered it was found that increasing the filtration pressure reduced the flux of cytochrome c across the films. A similar phenomenon occurred when serum was filtered, less protein passed through the films at high filtration pressures. These phenomena are explained by concentration-polarisation effects. 4. The flux of cytochrome c through the films was found to decrease in a non-linear manner as the films thickness was increased. With thin films, the flux of cytochrome c increased in a non-linear manner as the concentration of the protein in the overstanding solution was increased. With thicker films the flux was linearly dependent on concentration. These findings are interpreted as supporting the view that movement of cytochrome c occurs, at least in part, by convective flow."}
{"id": "PMID:218631", "title": "Activation and inhibition of lipoprotein lipase. Studies with artificial lipoproteins.", "content": "Human plasma very low density apolipoproteins C-I, C-II and C-III were recombined in vitro with triolein. The lipid-protein complexes were analyzed by ultracentrifugal flotation, agarose gel electrophoresis, immunoelectrophoresis and electron microscopy. Maximal protein/triolein ratios for apoprotein C-I, C-II, C-III-1 and C-III-2 were 50, 45, 95 and 55 microgram/mg, respectively. Electron micrographs exhibited spherical particles with diameters ranging from 200--2000 A comparable to native VLDL and chylomicrons. On agarose gel electrophoresis these complexes showed alpha-mobility. Kinetics of triolein hydrolysis by purified human plasma lipoprotein lipase were studied using these artificial lipoprotein substrates with different apoprotein/triolein ratios. The reaction followed the Michaelis-Menten equation. With increasing amounts of apo C-II, the apparent Km decreased from 0.60 to 0.11 mM. Incubation of the substrate with either rabbit anti-apo C-II gamma-globulins or digestion with trypsin prior to hydrolysis reversed this lowering effect on apparent Km. V was not altered significantly. Increasing amounts of apo C-I, apo C-III-1 or apo C-III-2 without apo C-II caused inhibition of triolein hydrolysis. In the presence of apo C-II, however, similar kinetic parameters were obtained as described above.", "contents": "Activation and inhibition of lipoprotein lipase. Studies with artificial lipoproteins. Human plasma very low density apolipoproteins C-I, C-II and C-III were recombined in vitro with triolein. The lipid-protein complexes were analyzed by ultracentrifugal flotation, agarose gel electrophoresis, immunoelectrophoresis and electron microscopy. Maximal protein/triolein ratios for apoprotein C-I, C-II, C-III-1 and C-III-2 were 50, 45, 95 and 55 microgram/mg, respectively. Electron micrographs exhibited spherical particles with diameters ranging from 200--2000 A comparable to native VLDL and chylomicrons. On agarose gel electrophoresis these complexes showed alpha-mobility. Kinetics of triolein hydrolysis by purified human plasma lipoprotein lipase were studied using these artificial lipoprotein substrates with different apoprotein/triolein ratios. The reaction followed the Michaelis-Menten equation. With increasing amounts of apo C-II, the apparent Km decreased from 0.60 to 0.11 mM. Incubation of the substrate with either rabbit anti-apo C-II gamma-globulins or digestion with trypsin prior to hydrolysis reversed this lowering effect on apparent Km. V was not altered significantly. Increasing amounts of apo C-I, apo C-III-1 or apo C-III-2 without apo C-II caused inhibition of triolein hydrolysis. In the presence of apo C-II, however, similar kinetic parameters were obtained as described above."}
{"id": "PMID:218632", "title": "Effects of estrogen administration on the lipoproteins and apoproteins of the chicken.", "content": "The plasma lipoproteins of estrogen-treated and untreated sexually immature hens have been compared with respect to their concentration in plasma, protein and lipid composition, particle size, and and apoprotein composition. Administration of diethylstilbestrol resulted in a 400-fold rise in the concentration of very low density lipoprotein (VLDL), a 70-fold rise in low density lipoprotein (LDL), and a marked reduction in high density lipoprotein (HDL) protein. It also resulted in the production of LDL and HDL which were enriched in triacylglycerol, while the proportion of cholesterol in all three lipoprotein fractions decreased. In contrast to the lipoproteins from untreated birds, lipoproteins of density less than 1.06 g/ml from estrogen-treated birds were not clearly separable into discrete VLDL and LDL fractions, but appeared to be a single ultracentrifugal class. The apoprotein composition of VLDL and LDL from untreated birds differed from each other; however, the apoprotein patterns of VLDL and LDL from estrogen-treated birds were indistinguishable: both contained a large amount of low molecular weight protein in addition to the high molecular weight component that predominates in the untreated state. The apoprotein composition of HDL was also markedly altered by estrogen administration: the 28,000 mol. wt. protein (apo A-I) decreased in amount from 65% to less than 5% of the total, while a low molecular weight (Mr = 14,000) protein and as yet poorly defined high molecular weight components became predominant. These observations indicate that the hyperlipidemia induced by estrogen administration is accompanied by marked alterations, both qualitative and quantitative, in the plasma lipoproteins.", "contents": "Effects of estrogen administration on the lipoproteins and apoproteins of the chicken. The plasma lipoproteins of estrogen-treated and untreated sexually immature hens have been compared with respect to their concentration in plasma, protein and lipid composition, particle size, and and apoprotein composition. Administration of diethylstilbestrol resulted in a 400-fold rise in the concentration of very low density lipoprotein (VLDL), a 70-fold rise in low density lipoprotein (LDL), and a marked reduction in high density lipoprotein (HDL) protein. It also resulted in the production of LDL and HDL which were enriched in triacylglycerol, while the proportion of cholesterol in all three lipoprotein fractions decreased. In contrast to the lipoproteins from untreated birds, lipoproteins of density less than 1.06 g/ml from estrogen-treated birds were not clearly separable into discrete VLDL and LDL fractions, but appeared to be a single ultracentrifugal class. The apoprotein composition of VLDL and LDL from untreated birds differed from each other; however, the apoprotein patterns of VLDL and LDL from estrogen-treated birds were indistinguishable: both contained a large amount of low molecular weight protein in addition to the high molecular weight component that predominates in the untreated state. The apoprotein composition of HDL was also markedly altered by estrogen administration: the 28,000 mol. wt. protein (apo A-I) decreased in amount from 65% to less than 5% of the total, while a low molecular weight (Mr = 14,000) protein and as yet poorly defined high molecular weight components became predominant. These observations indicate that the hyperlipidemia induced by estrogen administration is accompanied by marked alterations, both qualitative and quantitative, in the plasma lipoproteins."}
{"id": "PMID:218633", "title": "Very low density and low density lipoprotein subfractions in type III and type IV hyperlipoproteinemia. Chemical and physical properties.", "content": "Subfractions of CLDL (VLDL), Sf 100-400; CLDL2, Sf 60--100; VLDL3, Sf 20--60) and LDL (LDL), Sf 12--20; LDL2, Sf 6--12; LDL3, Sf 3--6) were isolated from the plasma of three normal, three type III and four type IV hyperlipoproteinemic subjects. In the type IV group, all VLDL subspecies were of normal composition but were increased in concentration in the order VLDL1 greater than VLDL2 greater than VLDL3. In the same subjects, although LDL2 was lowered and LDL3 increased, the total plasma LDL concentration was normal. All VLDL subfractions were elevated in the type III group, but in this case VLDL3 predominated. These subfractions were enriched in cholesteryl esters and depleted in triglyceride. In the LDL density range there was a shift of mass towards the least dense fraction, LDL1, which was of normal composition. EPR studies of the VLDL and LDL subfractions in a type IV subject demonstrated a decrease in fluidity with increasing density. The major change occurred between VLDL3 and LDL1 and was attributed to a substantial alteration in the cholesteryl ester : triglyceride ratio in the particle. A similar argument was used to explain thction in normal or type IV subjects. Particle diameters, determined by laser light-scattering spectroscopy were in good agreement with the values obtained by electron microscopy. This study provides a baseline for the examination of the relationship between the physical and metabolic properties of VLDL and LDL subfractions in type III and IV hyperlipoproteinemia.", "contents": "Very low density and low density lipoprotein subfractions in type III and type IV hyperlipoproteinemia. Chemical and physical properties. Subfractions of CLDL (VLDL), Sf 100-400; CLDL2, Sf 60--100; VLDL3, Sf 20--60) and LDL (LDL), Sf 12--20; LDL2, Sf 6--12; LDL3, Sf 3--6) were isolated from the plasma of three normal, three type III and four type IV hyperlipoproteinemic subjects. In the type IV group, all VLDL subspecies were of normal composition but were increased in concentration in the order VLDL1 greater than VLDL2 greater than VLDL3. In the same subjects, although LDL2 was lowered and LDL3 increased, the total plasma LDL concentration was normal. All VLDL subfractions were elevated in the type III group, but in this case VLDL3 predominated. These subfractions were enriched in cholesteryl esters and depleted in triglyceride. In the LDL density range there was a shift of mass towards the least dense fraction, LDL1, which was of normal composition. EPR studies of the VLDL and LDL subfractions in a type IV subject demonstrated a decrease in fluidity with increasing density. The major change occurred between VLDL3 and LDL1 and was attributed to a substantial alteration in the cholesteryl ester : triglyceride ratio in the particle. A similar argument was used to explain thction in normal or type IV subjects. Particle diameters, determined by laser light-scattering spectroscopy were in good agreement with the values obtained by electron microscopy. This study provides a baseline for the examination of the relationship between the physical and metabolic properties of VLDL and LDL subfractions in type III and IV hyperlipoproteinemia."}
{"id": "PMID:218634", "title": "An oxygen-binding flavohemoprotein from Alcaligenes eutrophus.", "content": "A procedure is described for the purification of a soluble flavohemoprotein from the hydrogen bacterium Alcaligenes eutrophus. The isolated protein exists as a monomer with a molecular weight of approx. 43,000. The molecule contains two prosthetic groups, 1 mol each of noncovalently bound FAD and protoheme per monomer. The absorption spectra of the protein in its ferric, ferrous-deoxy and ferrous-carboxy forms are similar to those of hemoglobins, with the exception of the flavin contribution (absorption maxima--ferric form: 395, 456, 483, 645 nm; ferrous-deoxy form: 436, 560 nm; ferrour-CO form: 423, 539, 569 nm). The flavohemoprotein when reduced by NADH in aerobic solution is capable of binding oxygen reversibly. The stable oxygenated complex exhibits absorption maxima at 414, 541, and 576 nm. The protein catalyzes the reduction of various dyes and cytochrome c by NADH.", "contents": "An oxygen-binding flavohemoprotein from Alcaligenes eutrophus. A procedure is described for the purification of a soluble flavohemoprotein from the hydrogen bacterium Alcaligenes eutrophus. The isolated protein exists as a monomer with a molecular weight of approx. 43,000. The molecule contains two prosthetic groups, 1 mol each of noncovalently bound FAD and protoheme per monomer. The absorption spectra of the protein in its ferric, ferrous-deoxy and ferrous-carboxy forms are similar to those of hemoglobins, with the exception of the flavin contribution (absorption maxima--ferric form: 395, 456, 483, 645 nm; ferrous-deoxy form: 436, 560 nm; ferrour-CO form: 423, 539, 569 nm). The flavohemoprotein when reduced by NADH in aerobic solution is capable of binding oxygen reversibly. The stable oxygenated complex exhibits absorption maxima at 414, 541, and 576 nm. The protein catalyzes the reduction of various dyes and cytochrome c by NADH."}
{"id": "PMID:218635", "title": "M\u00f6ssbauer studies of cytochrome c-551. Intrinsic heterogeneity related to g-strain.", "content": "The M\u00f6ssbauer spectra of oxidized and reduced cytochrome c-551 from Pseudomonas aeruginosa are analyzed. Excess broadening is observed in the 4.2 K spectra of oxidized c-551 which is consistent with a Gaussian distribution of the crystal field parameters delta and R as inferred from the g-strain model of EPR line shapes.", "contents": "M\u00f6ssbauer studies of cytochrome c-551. Intrinsic heterogeneity related to g-strain. The M\u00f6ssbauer spectra of oxidized and reduced cytochrome c-551 from Pseudomonas aeruginosa are analyzed. Excess broadening is observed in the 4.2 K spectra of oxidized c-551 which is consistent with a Gaussian distribution of the crystal field parameters delta and R as inferred from the g-strain model of EPR line shapes."}
{"id": "PMID:218636", "title": "Electron paramagnetic resonance studies of the purified cytochrome P-450scc and P-45011beta from bovine adrenocortical mitochondria.", "content": "Electron paramagnetic resonance studies have been carried out on two species of cytochrome P-450 (P-450scc and P-45011beta) purified from bovine adrenocortical mitochondria. The g values of the steroid-bound cytochromes in the high spin form were determined at 4.2 degrees K to be 8.07, 3.60 and 1.70 for P-450scc and 8.00, 3.65 and 1.71 for P-45011beta. The E/D values were estimated to be 0.103 for P-450scc and 0.099 for P-45011beta. Either high spin P-450 was converted into the low spin form by the treatment with an NADPH dependent electron donating system and subsequent gel filtration in order to remove the steroid. The g values of the low spin ferric cytochromes were 2.423, 2.247 and 1.914 for P-450scc and 2.430, 2.251 and 1.919 for P-45011beta at 77 degrees K. The values for magnitude of delta/gamma, magnitude of V/gamma and k were 5.69, 5.21 and 1.11 for P-450scc and 5.94, 5.38 and 1.16 for P-45011beta. These studies indicate that there are some differences in the ferric heme environment between P-450scc and P-45011beta.", "contents": "Electron paramagnetic resonance studies of the purified cytochrome P-450scc and P-45011beta from bovine adrenocortical mitochondria. Electron paramagnetic resonance studies have been carried out on two species of cytochrome P-450 (P-450scc and P-45011beta) purified from bovine adrenocortical mitochondria. The g values of the steroid-bound cytochromes in the high spin form were determined at 4.2 degrees K to be 8.07, 3.60 and 1.70 for P-450scc and 8.00, 3.65 and 1.71 for P-45011beta. The E/D values were estimated to be 0.103 for P-450scc and 0.099 for P-45011beta. Either high spin P-450 was converted into the low spin form by the treatment with an NADPH dependent electron donating system and subsequent gel filtration in order to remove the steroid. The g values of the low spin ferric cytochromes were 2.423, 2.247 and 1.914 for P-450scc and 2.430, 2.251 and 1.919 for P-45011beta at 77 degrees K. The values for magnitude of delta/gamma, magnitude of V/gamma and k were 5.69, 5.21 and 1.11 for P-450scc and 5.94, 5.38 and 1.16 for P-45011beta. These studies indicate that there are some differences in the ferric heme environment between P-450scc and P-45011beta."}
{"id": "PMID:218637", "title": "An assessment of the role of protein kinase and zymogen granule phosphorylation during secretion by the rat exocrine pancreas.", "content": "1. The levels of protein kinase activity and zymogen granule phosphorylation were studied in the adult rat during stimulus-coupled secretion in vitro. 2. The specific activity of protein kinase associated with intact zymogen granules was 11 pmol [32P]phosphate transferred to histone per min per mg protein. Most of this activity was recovered in purified granule membranes. 2. The addition of 10(-6) M cyclic AMP to a mixture of zymogen granules and the postmicrosomal supernatant resulted in a 5-fold increase in protein kinase activity associated with zymogen granules. The adsorbed activity was eluted from granules by 0.15 M NaCl. Cyclic GMP did not promote protein kinase binding to isolated granules. 4. Incubation of tissues with carbachol (10(-5) M), pancreozymin (0.1 unit/ml), caerulein (10(-8) M) or dibutyryl cyclic AMP (2.10(-4) M) between 2.5 and 60 min did not increase the levels of protein kinase activity in isolated zymogen granules above control values. 5. Protein phosphorylation of zymogen granule membranes and granule content was not detectable in tissues incubated with carbachol, pancreozymin-C-octapeptide, or caerulein. 6. These results suggest that neither the phosphorylation of zymogen granule membrane protein nor the adsorption of protein kinase activity to zymogen granules is an obligatory step in secretion.", "contents": "An assessment of the role of protein kinase and zymogen granule phosphorylation during secretion by the rat exocrine pancreas. 1. The levels of protein kinase activity and zymogen granule phosphorylation were studied in the adult rat during stimulus-coupled secretion in vitro. 2. The specific activity of protein kinase associated with intact zymogen granules was 11 pmol [32P]phosphate transferred to histone per min per mg protein. Most of this activity was recovered in purified granule membranes. 2. The addition of 10(-6) M cyclic AMP to a mixture of zymogen granules and the postmicrosomal supernatant resulted in a 5-fold increase in protein kinase activity associated with zymogen granules. The adsorbed activity was eluted from granules by 0.15 M NaCl. Cyclic GMP did not promote protein kinase binding to isolated granules. 4. Incubation of tissues with carbachol (10(-5) M), pancreozymin (0.1 unit/ml), caerulein (10(-8) M) or dibutyryl cyclic AMP (2.10(-4) M) between 2.5 and 60 min did not increase the levels of protein kinase activity in isolated zymogen granules above control values. 5. Protein phosphorylation of zymogen granule membranes and granule content was not detectable in tissues incubated with carbachol, pancreozymin-C-octapeptide, or caerulein. 6. These results suggest that neither the phosphorylation of zymogen granule membrane protein nor the adsorption of protein kinase activity to zymogen granules is an obligatory step in secretion."}
{"id": "PMID:218638", "title": "Investigation of the subcellular distribution of cyclic-AMP phosphodiesterase in rat hepatocytes, using a rapid immunological procedure for the isolation of plasma membrane.", "content": "The distribution of cyclic-AMP phosphodiesterase was investigated in subcellular fractions prepared from homogenates of rat liver or isolated hepatocytes. When measured at 1 mM or 1 microM substrate concentration, approx. 35% or 50%, respectively, of enzyme activity was particulate. The soluble activity appeared to be predominantly a 'high Km' form, whereas the particulate activity had both 'high Km' and 'low Km' components. The recovery of cyclic-AMP phosphodiesterase was measured using 1 microM substrate concentraiton, in plasma membrane-containing fractions prepared either by centrifugation or by the use of specific immunoadsorbents. The recovery of phosphodiesterase was lower than that of marker enzymes for plasma membrane, and comparable with the recovery of markers for intracellular membranes. It was concluded that regulation of both 'high Km' and 'low Km' phosphodiesterase could potentially make a significant contribution to the control of cyclic AMP concentration, even at microM levels, in the liver. the 'low Km' enzyme, for which activation by hormones has been previously described, appears to be located predominantly in intracellular membranes in hepatocytes. The immunological procedure for membrane isolation allowed the rapid preparation of plasma membranes in high yield. Liver cells were incubated with rabbit anti-(rat erythrocyte) serum and homogenized. The antibody-coated membrane fragments were then extracted onto an immunoadsorbent consisting of sheep anti-(rabbit IgG) immunoglobulin covalently bound to aminocellulose. Plasma membrane was obtained in approx. 40% yield within 50 min of homogenizing cells.", "contents": "Investigation of the subcellular distribution of cyclic-AMP phosphodiesterase in rat hepatocytes, using a rapid immunological procedure for the isolation of plasma membrane. The distribution of cyclic-AMP phosphodiesterase was investigated in subcellular fractions prepared from homogenates of rat liver or isolated hepatocytes. When measured at 1 mM or 1 microM substrate concentration, approx. 35% or 50%, respectively, of enzyme activity was particulate. The soluble activity appeared to be predominantly a 'high Km' form, whereas the particulate activity had both 'high Km' and 'low Km' components. The recovery of cyclic-AMP phosphodiesterase was measured using 1 microM substrate concentraiton, in plasma membrane-containing fractions prepared either by centrifugation or by the use of specific immunoadsorbents. The recovery of phosphodiesterase was lower than that of marker enzymes for plasma membrane, and comparable with the recovery of markers for intracellular membranes. It was concluded that regulation of both 'high Km' and 'low Km' phosphodiesterase could potentially make a significant contribution to the control of cyclic AMP concentration, even at microM levels, in the liver. the 'low Km' enzyme, for which activation by hormones has been previously described, appears to be located predominantly in intracellular membranes in hepatocytes. The immunological procedure for membrane isolation allowed the rapid preparation of plasma membranes in high yield. Liver cells were incubated with rabbit anti-(rat erythrocyte) serum and homogenized. The antibody-coated membrane fragments were then extracted onto an immunoadsorbent consisting of sheep anti-(rabbit IgG) immunoglobulin covalently bound to aminocellulose. Plasma membrane was obtained in approx. 40% yield within 50 min of homogenizing cells."}
{"id": "PMID:218639", "title": "Transferrin receptors on human B and T lymphoblastoid cell lines.", "content": "Experiments demonstrating the existence of receptors for iron-saturated transferrin on both B and T lymphoblastoid cell lines of human origin are described. Binding of 125I-labeled transferrin is rapid, saturable and reversible. It can be specifically inhibited by unlabeled transferrin but not by other proteins. The number of receptors on T cell lines determined by Scatchard analysis is almost double the number on B cell lines but the binding affinities are equal. The putative transferrin receptor can be removed from the cell by the proteolytic enzymes papain and trypsin, and is re-expressed during overnight incubation at 37 degrees C. Resynthesis is inhibited by puromycin. The receptor can be solubilized by deoxycholate, and retains transferrin binding capacity when non-covalently attached to an amphipathic matrix consisting of deoxycholate-coupled poly(L-lysyl) Agarose.", "contents": "Transferrin receptors on human B and T lymphoblastoid cell lines. Experiments demonstrating the existence of receptors for iron-saturated transferrin on both B and T lymphoblastoid cell lines of human origin are described. Binding of 125I-labeled transferrin is rapid, saturable and reversible. It can be specifically inhibited by unlabeled transferrin but not by other proteins. The number of receptors on T cell lines determined by Scatchard analysis is almost double the number on B cell lines but the binding affinities are equal. The putative transferrin receptor can be removed from the cell by the proteolytic enzymes papain and trypsin, and is re-expressed during overnight incubation at 37 degrees C. Resynthesis is inhibited by puromycin. The receptor can be solubilized by deoxycholate, and retains transferrin binding capacity when non-covalently attached to an amphipathic matrix consisting of deoxycholate-coupled poly(L-lysyl) Agarose."}
{"id": "PMID:218640", "title": "Interaction of secretin5-27 and its analogues with hormone receptors on pancreatic acini.", "content": "The C-terminal tricosapeptide of secretin (S5-27) and two analogues, one with asparagine replacing aspartic acid in position 15 (15-Asn-S5--27) and one with lysine replacing aspartic acid in position 15 (15-Lys-S5-27) were tested for their abilities to interact with hormone receptors on pancreatic acinar cells. In interacting with the receptors which prefer vasoactive intestinal peptide (vasoactive intestinal peptide-preferring receptors), the apparent affinity of 15-Asn S5-27 was equal to that of 15-Lys-S5-27 and was greater than that of S5-27. In interacting with secretin-preferring receptors, the apparent affinity of 15-Asn-S5--27 was equal to that of S5-27 and was greater than that of 15-Lys-S5-27. In interacting with the secretin-preferring receptors each of the secretin fragments was approximately 2% as effective as secretin in causing an increase in cellular cyclic AMP. None of these fragments was able to cause a detectable increase in cyclic AMP mediated by the vasoactive intestinal peptide-preferring receptors. The dose vs. response curves for the action of secretin and vasoactive intestinal peptide on cellular cyclic AMP and on amylase secretion as well as the pattern of effects of secretin fragments on these actions indicated that the increase in amylase secretion caused by vasoactive intestinal peptide and secretin is mediated exclusively by the vasoactive intestinal peptide-preferring receptors. Furthermore, occupation of approximately 50% of the vasoactive intestinal peptide-preferring receptors is sufficient to cause maximal stimulation of amylase secretion.", "contents": "Interaction of secretin5-27 and its analogues with hormone receptors on pancreatic acini. The C-terminal tricosapeptide of secretin (S5-27) and two analogues, one with asparagine replacing aspartic acid in position 15 (15-Asn-S5--27) and one with lysine replacing aspartic acid in position 15 (15-Lys-S5-27) were tested for their abilities to interact with hormone receptors on pancreatic acinar cells. In interacting with the receptors which prefer vasoactive intestinal peptide (vasoactive intestinal peptide-preferring receptors), the apparent affinity of 15-Asn S5-27 was equal to that of 15-Lys-S5-27 and was greater than that of S5-27. In interacting with secretin-preferring receptors, the apparent affinity of 15-Asn-S5--27 was equal to that of S5-27 and was greater than that of 15-Lys-S5-27. In interacting with the secretin-preferring receptors each of the secretin fragments was approximately 2% as effective as secretin in causing an increase in cellular cyclic AMP. None of these fragments was able to cause a detectable increase in cyclic AMP mediated by the vasoactive intestinal peptide-preferring receptors. The dose vs. response curves for the action of secretin and vasoactive intestinal peptide on cellular cyclic AMP and on amylase secretion as well as the pattern of effects of secretin fragments on these actions indicated that the increase in amylase secretion caused by vasoactive intestinal peptide and secretin is mediated exclusively by the vasoactive intestinal peptide-preferring receptors. Furthermore, occupation of approximately 50% of the vasoactive intestinal peptide-preferring receptors is sufficient to cause maximal stimulation of amylase secretion."}
{"id": "PMID:218641", "title": "Anomalies of cyclic AMP excretion in some abnormal offenders.", "content": "It is now well established that the metabolic sequeale of catecholamine secretion are mediated via cyclic nucleotides. Recent studies have indicated changes in the pattern of catecholamine secretion correlating with convictions for violence in maximum security hospital detainees. This study of the excretion rate of urinary cyclic AMP in this group of patients failed to show a correlation between adrenaline or noradrenaline and cyclic AMP secretion. However, subjects convicted of sexual offences showed a significantly greater cyclic AMP excretion than other patients and normal controls. These results are discussed in terms of the possible modification of receptor sensitivity and influence of alternative agonists such as testosterone.", "contents": "Anomalies of cyclic AMP excretion in some abnormal offenders. It is now well established that the metabolic sequeale of catecholamine secretion are mediated via cyclic nucleotides. Recent studies have indicated changes in the pattern of catecholamine secretion correlating with convictions for violence in maximum security hospital detainees. This study of the excretion rate of urinary cyclic AMP in this group of patients failed to show a correlation between adrenaline or noradrenaline and cyclic AMP secretion. However, subjects convicted of sexual offences showed a significantly greater cyclic AMP excretion than other patients and normal controls. These results are discussed in terms of the possible modification of receptor sensitivity and influence of alternative agonists such as testosterone."}
{"id": "PMID:218642", "title": "Behavioral and psychophysiological correlates of irregularity in chronic sleep routines.", "content": "Behavioral and psychophysiological correlates of irregularity in chronic sleep routines were studied. Two groups each of 18 healthy male university students were classified as either irregular sleepers or control subjects according to retrospective questionnaires, and sleep chart criteria. The control group was composed of persons who slept naturally from 12-8:00 a.m. for 7-8 hr. Irregular sleepers were defined as those whose retiring and awakening times varied by about 2-4 hr. Measurements were obtained from an auditory reaction time task, a mood adjective check list, of sublingual temperature and pulse rate 30 min. after awakening in the (a) morning, at (b) noon, in the (c) afternoon and (d) early evening following an electroencephalographically recorded 12-8:00 a.m. sleep night. At various points in the diurnal cycle irregular sleepers compared with the control group had significantly lower levels of pulse rate and body temperature, but significantly longer reaction times. During the four time periods negative affects (deactivation-sleep, depression, general deactivation, inert-fatigued) were significantly greater and positive mood states (cheerful, energetic, general activation--significantly less in the irregular sleepers. The irregular sleepers averaged significantly less stage 4, and REM, but more stage 2 and transitions between sleep stages. The present results indicate that relatively lowered levels of physiological arousal indexes, psychomotor performance and subjective mood are associated with irregularity in chronic sleep routines of young adult males. These psychobehavioral correlates of chronically maintained sleep pattern variations complement and extend previous findings on degradations in waking functions following acute 2-4 hr temporal shifts of habitual sleep periods. It is postulated that there were psychobehavioral deficits in the irregular sleepers attributable either to selective sleep stage (REM and/or stage 4) deprivation or to the more general consequence of disturbed sleeping patterns per se or to both of these factors.", "contents": "Behavioral and psychophysiological correlates of irregularity in chronic sleep routines. Behavioral and psychophysiological correlates of irregularity in chronic sleep routines were studied. Two groups each of 18 healthy male university students were classified as either irregular sleepers or control subjects according to retrospective questionnaires, and sleep chart criteria. The control group was composed of persons who slept naturally from 12-8:00 a.m. for 7-8 hr. Irregular sleepers were defined as those whose retiring and awakening times varied by about 2-4 hr. Measurements were obtained from an auditory reaction time task, a mood adjective check list, of sublingual temperature and pulse rate 30 min. after awakening in the (a) morning, at (b) noon, in the (c) afternoon and (d) early evening following an electroencephalographically recorded 12-8:00 a.m. sleep night. At various points in the diurnal cycle irregular sleepers compared with the control group had significantly lower levels of pulse rate and body temperature, but significantly longer reaction times. During the four time periods negative affects (deactivation-sleep, depression, general deactivation, inert-fatigued) were significantly greater and positive mood states (cheerful, energetic, general activation--significantly less in the irregular sleepers. The irregular sleepers averaged significantly less stage 4, and REM, but more stage 2 and transitions between sleep stages. The present results indicate that relatively lowered levels of physiological arousal indexes, psychomotor performance and subjective mood are associated with irregularity in chronic sleep routines of young adult males. These psychobehavioral correlates of chronically maintained sleep pattern variations complement and extend previous findings on degradations in waking functions following acute 2-4 hr temporal shifts of habitual sleep periods. It is postulated that there were psychobehavioral deficits in the irregular sleepers attributable either to selective sleep stage (REM and/or stage 4) deprivation or to the more general consequence of disturbed sleeping patterns per se or to both of these factors."}
{"id": "PMID:218643", "title": "Adult coeliac disease, osteomalacia, hyperparathyroidism and acromegaly. Evidence for urinary losses of hydrosoluble metabolites of vitamin D3.", "content": "Vitamin D-deficient osteomalacia with pronounced secondary hyperparathyroidism was observed in an acromegalic patient suffering from adult celiac disease. Two oral tests with tritiated vitamin D3 showed a nearly normal absorption coefficient, contrasting with a marked steatorrhea mainly due to functional and reversible pancreatic insufficiency. The urinary excretion of the radioactive label was strikingly increased and accounted for the completely flat curve of plasma radioactivity. This urinary loss of mainly water-soluble metabolite(s) of vitamin D3 represents a unique and presently unexplained feature.", "contents": "Adult coeliac disease, osteomalacia, hyperparathyroidism and acromegaly. Evidence for urinary losses of hydrosoluble metabolites of vitamin D3. Vitamin D-deficient osteomalacia with pronounced secondary hyperparathyroidism was observed in an acromegalic patient suffering from adult celiac disease. Two oral tests with tritiated vitamin D3 showed a nearly normal absorption coefficient, contrasting with a marked steatorrhea mainly due to functional and reversible pancreatic insufficiency. The urinary excretion of the radioactive label was strikingly increased and accounted for the completely flat curve of plasma radioactivity. This urinary loss of mainly water-soluble metabolite(s) of vitamin D3 represents a unique and presently unexplained feature."}
{"id": "PMID:218644", "title": "Action of dopamine on cyclic AMP-tissue level in the rat pancreas. Interaction with secretin.", "content": "Dopamine increased the cyclic AMP content of rat pancreas slices. It only partially displayed the agonist activity of secretin. Haloperidol 10(-4)M, a dopamine blocking agent almost completely inhibited the response to dopamine but had no effect on the response to secretin. Dopamine 10(-3)M, increased the cyclic AMP level induced by a low concentration of secretin and inhibited the production of cyclic AMP observed with a high concentration of secretin. Our data suggest that dopamine in the rat pancreatic tissue does not interfere with the secretin receptor but might act on the same adenylate cyclase.", "contents": "Action of dopamine on cyclic AMP-tissue level in the rat pancreas. Interaction with secretin. Dopamine increased the cyclic AMP content of rat pancreas slices. It only partially displayed the agonist activity of secretin. Haloperidol 10(-4)M, a dopamine blocking agent almost completely inhibited the response to dopamine but had no effect on the response to secretin. Dopamine 10(-3)M, increased the cyclic AMP level induced by a low concentration of secretin and inhibited the production of cyclic AMP observed with a high concentration of secretin. Our data suggest that dopamine in the rat pancreatic tissue does not interfere with the secretin receptor but might act on the same adenylate cyclase."}
{"id": "PMID:218645", "title": "Fluorescence studies of the interaction between 1,N6-ethenoadenosine monophosphate and nucleotides.", "content": "AMP, GMP, TMP and CMP quench the fluorescence of 1,N6-ethenoadenosine monophosphate (epsilon-AMP). The fluorescence spectrum of epsilon-AMP-nucleotide system is identical with that of epsilon-AMP itself, and the fluorescence decay kinetics follow a single-exponential decay law. The dependence of fluorescence yields and lifetimes upon the concentration of nucleotides shows that the fluorescence of epsilon-AMP is principally quenched in a dynamic process by AMP, TMP and CMP, while it is quenched in both dynamic and static processes by GMP. The quenching constants increase in the following order: GMP greater than AMP greater than TMP greater than CMP.", "contents": "Fluorescence studies of the interaction between 1,N6-ethenoadenosine monophosphate and nucleotides. AMP, GMP, TMP and CMP quench the fluorescence of 1,N6-ethenoadenosine monophosphate (epsilon-AMP). The fluorescence spectrum of epsilon-AMP-nucleotide system is identical with that of epsilon-AMP itself, and the fluorescence decay kinetics follow a single-exponential decay law. The dependence of fluorescence yields and lifetimes upon the concentration of nucleotides shows that the fluorescence of epsilon-AMP is principally quenched in a dynamic process by AMP, TMP and CMP, while it is quenched in both dynamic and static processes by GMP. The quenching constants increase in the following order: GMP greater than AMP greater than TMP greater than CMP."}
{"id": "PMID:218646", "title": "Quantitative aspects of a unified model of diffusion mediated receptor--cyclase coupling.", "content": "A quantitative model is presented of diffusion mediated coupling of adenylate cyclase to multivalent plasma membrane receptors which accounts for a wide range of phenomena including non linear occupation-activation plots with either positive or negative second derivatives, spare receptors, silent receptors, and negative and positive binding cooperativity. A non linear least square fit of the predicted equation for cyclase activation to available data predicts translational diffusion coefficients in the range of (10(-10) - 10(-11))cm2/s.", "contents": "Quantitative aspects of a unified model of diffusion mediated receptor--cyclase coupling. A quantitative model is presented of diffusion mediated coupling of adenylate cyclase to multivalent plasma membrane receptors which accounts for a wide range of phenomena including non linear occupation-activation plots with either positive or negative second derivatives, spare receptors, silent receptors, and negative and positive binding cooperativity. A non linear least square fit of the predicted equation for cyclase activation to available data predicts translational diffusion coefficients in the range of (10(-10) - 10(-11))cm2/s."}
{"id": "PMID:218647", "title": "Early molecular events in the interaction of enveloped viruses with cells. I. A fluorescence and radioactivity study.", "content": "The fluorescence depolarization of 1,6-diphenyl-hexatriene was used to study the dynamic properties of the hydrophobic regions of the lipid envelopes of ortho- and paramyxoviruses as well as of the Rous sarcoma virus and of the membrane lipids of susceptible and nonsusceptible cells. The systems investigated where active and inactive influenza viruses, and NDV virus acting on chick embryo fibroblasts and Rous sarcoma virus acting on susceptible (C/E) and nonsusceptible (C/B) chicken-cell. Polarization degrees and mean rotational correlation times of DPH embedded in viral lipids were significantly higher than those of DPH in the cell membranes, due to a higher rigidity of the virus envelopes. When suspensions of labelled viruses and unlabelled cells or unlabelled viruses and labelled cells were mixed, a characteristic change of the fluorescence polarization degrees with time was observed. This behaviour was ascribed to label transfer from virus to cell membranes or vice versa. While the rate constants of label transfer from virus to cells and cells to virus were about the same for the penetrating viruses the rate constants of label release from inactive virus to cells were much larger than for the migration in the opposite direction.", "contents": "Early molecular events in the interaction of enveloped viruses with cells. I. A fluorescence and radioactivity study. The fluorescence depolarization of 1,6-diphenyl-hexatriene was used to study the dynamic properties of the hydrophobic regions of the lipid envelopes of ortho- and paramyxoviruses as well as of the Rous sarcoma virus and of the membrane lipids of susceptible and nonsusceptible cells. The systems investigated where active and inactive influenza viruses, and NDV virus acting on chick embryo fibroblasts and Rous sarcoma virus acting on susceptible (C/E) and nonsusceptible (C/B) chicken-cell. Polarization degrees and mean rotational correlation times of DPH embedded in viral lipids were significantly higher than those of DPH in the cell membranes, due to a higher rigidity of the virus envelopes. When suspensions of labelled viruses and unlabelled cells or unlabelled viruses and labelled cells were mixed, a characteristic change of the fluorescence polarization degrees with time was observed. This behaviour was ascribed to label transfer from virus to cell membranes or vice versa. While the rate constants of label transfer from virus to cells and cells to virus were about the same for the penetrating viruses the rate constants of label release from inactive virus to cells were much larger than for the migration in the opposite direction."}
{"id": "PMID:218648", "title": "Early molecular events during the interaction of enveloped riboviruses with cells. II. A kinetic study.", "content": "A kinetic model was constructed and partly solved to describe the migration of the fluorescence label 1,6-diphenylhexatriene (DPH) in both directions when enveloped viruses, labelled with DPH in their envelopes are in contact with unlabelled cells or cell labelled in their membranes are in contact with unlabelled enveloped viruses. The central assumption is that two types of receptor sites exist on the cell surface, i.e., physical adsorption sites (P-sites), available to all the viruses studied in these papers and binding sites (B-sites) available only to the viruses which penetrate into the specific cells. The differential equations for the label migration, for different values of the ratio number of viruses number of sites were numerically solved, assuming different fractions of P- and B-sites. The equations also describe, appropriately the mechanism of rapid label migration in the system and substantiate the magnitude \"time of residence\" of the nonpenetrating viruses adsorbed on the cell surface. The resulting curves match satisfactorily those for the label release by the viruses and account well for the steady state values of the kinetics of label migration in the virus-cell system.", "contents": "Early molecular events during the interaction of enveloped riboviruses with cells. II. A kinetic study. A kinetic model was constructed and partly solved to describe the migration of the fluorescence label 1,6-diphenylhexatriene (DPH) in both directions when enveloped viruses, labelled with DPH in their envelopes are in contact with unlabelled cells or cell labelled in their membranes are in contact with unlabelled enveloped viruses. The central assumption is that two types of receptor sites exist on the cell surface, i.e., physical adsorption sites (P-sites), available to all the viruses studied in these papers and binding sites (B-sites) available only to the viruses which penetrate into the specific cells. The differential equations for the label migration, for different values of the ratio number of viruses number of sites were numerically solved, assuming different fractions of P- and B-sites. The equations also describe, appropriately the mechanism of rapid label migration in the system and substantiate the magnitude \"time of residence\" of the nonpenetrating viruses adsorbed on the cell surface. The resulting curves match satisfactorily those for the label release by the viruses and account well for the steady state values of the kinetics of label migration in the virus-cell system."}
{"id": "PMID:218650", "title": "[Bioelectrical analysis of the regulatory interaction of sympathetic and parasympathetic nervous influences on the heart rhythm].", "content": "The changes of chronotropic effect on the isolated sinus node of the frog heart were studied during the separate and simultaneous stimulation of the sympathetic and intracardiac reflex parasympathetic pathways. Intracellular activity of the pacemaker cells was recorded. The separate stimulation of the intracardiac reflex system resulted in bradycardia (in winter) or tachycardia (in summer). Stimulation of sympathetic chain supervening the activation of the intracardiac pathways induced an intensification of both the parasympathetic bradycardia and tachycardia; these effects were cholinergic in nature. The recording of the intracellular pacemaker activity showed the existence of the complicated interaction between the sympathetic and parasympathetic pulse-mediator actions on the heart pacemaker both on the prepulase process and on the membrane polarization and other action potential parameters. Possible mechanisms of this interaction are discussed.", "contents": "[Bioelectrical analysis of the regulatory interaction of sympathetic and parasympathetic nervous influences on the heart rhythm]. The changes of chronotropic effect on the isolated sinus node of the frog heart were studied during the separate and simultaneous stimulation of the sympathetic and intracardiac reflex parasympathetic pathways. Intracellular activity of the pacemaker cells was recorded. The separate stimulation of the intracardiac reflex system resulted in bradycardia (in winter) or tachycardia (in summer). Stimulation of sympathetic chain supervening the activation of the intracardiac pathways induced an intensification of both the parasympathetic bradycardia and tachycardia; these effects were cholinergic in nature. The recording of the intracellular pacemaker activity showed the existence of the complicated interaction between the sympathetic and parasympathetic pulse-mediator actions on the heart pacemaker both on the prepulase process and on the membrane polarization and other action potential parameters. Possible mechanisms of this interaction are discussed."}
{"id": "PMID:218651", "title": "[Na, K-ATPase activity of the meninges in electroshock and the action of the anticonvulsant agent, diazepam].", "content": "It was shown that the phenomenon of inactivation of Na, K-ATPase of the non-purified fraction of the rat cortical synaptosomes under electroshock may be related to \"modification\" of the potassium active center of the enzyme. The anticonvulsant diazepam injected intramuscularly also inhibits Na, K-ATPase of the cerebral membranes. However, in subsequent electrical stimulation of the brain the drug activates Na, K-ATPase as compared to controls. Diazepam also abolishes clonic convulsions induced by electrical stimulation of the brain. At the same time it does not eliminate compensatory shifts in the activity of acetyl-cholinesterase of the rat cerebral and spinal synaptosomes, characteristic of electroshock. The results are discussed from the standpoint that inhibition of the activity of Na, K-ATPase of the nerve endings membranes may underlie the pathogenetic mechanism of the convulsive activity.", "contents": "[Na, K-ATPase activity of the meninges in electroshock and the action of the anticonvulsant agent, diazepam]. It was shown that the phenomenon of inactivation of Na, K-ATPase of the non-purified fraction of the rat cortical synaptosomes under electroshock may be related to \"modification\" of the potassium active center of the enzyme. The anticonvulsant diazepam injected intramuscularly also inhibits Na, K-ATPase of the cerebral membranes. However, in subsequent electrical stimulation of the brain the drug activates Na, K-ATPase as compared to controls. Diazepam also abolishes clonic convulsions induced by electrical stimulation of the brain. At the same time it does not eliminate compensatory shifts in the activity of acetyl-cholinesterase of the rat cerebral and spinal synaptosomes, characteristic of electroshock. The results are discussed from the standpoint that inhibition of the activity of Na, K-ATPase of the nerve endings membranes may underlie the pathogenetic mechanism of the convulsive activity."}
{"id": "PMID:218652", "title": "[Brain and kidney, Na, K-ATPase activation in the rat in adaptation to cold].", "content": "The activity of Na,K-ATPase of the rat brain and kidney is 1.5--2-fold as increased during intermittent and prolonged (16 weeks) adaptation to cold, without changes in the enzyme affinity to ATP. It is suggested that adaptive increase in the power of the Na pump, triidothyronine-dependent in the kidneys and triiodothyronine-independent in the brain, ensures elevation in thermal production to body cooling.", "contents": "[Brain and kidney, Na, K-ATPase activation in the rat in adaptation to cold]. The activity of Na,K-ATPase of the rat brain and kidney is 1.5--2-fold as increased during intermittent and prolonged (16 weeks) adaptation to cold, without changes in the enzyme affinity to ATP. It is suggested that adaptive increase in the power of the Na pump, triidothyronine-dependent in the kidneys and triiodothyronine-independent in the brain, ensures elevation in thermal production to body cooling."}
{"id": "PMID:218653", "title": "[Action of luliberine on the Na,K-ATPase and Ca-ATPase activity of the sarcolemma of the rat heart].", "content": "The effect of luliberine, one of the hypothalamic releasing-factors, upon the ATPase activity in the rat heart sarcolemma was investigated. A decrease in the (Na+-K+)-ATPase activity and stimulation of Ca-ATPase activity under the influence of luliberine were demonstrated. Inhibition of (Na+-K+)-ATPase by cAMP and noradrenaline was also revealed. A possibility of the direct and cAMP-mediated action of luliberine on the Na+-K+)-ATPase activity is suggested.", "contents": "[Action of luliberine on the Na,K-ATPase and Ca-ATPase activity of the sarcolemma of the rat heart]. The effect of luliberine, one of the hypothalamic releasing-factors, upon the ATPase activity in the rat heart sarcolemma was investigated. A decrease in the (Na+-K+)-ATPase activity and stimulation of Ca-ATPase activity under the influence of luliberine were demonstrated. Inhibition of (Na+-K+)-ATPase by cAMP and noradrenaline was also revealed. A possibility of the direct and cAMP-mediated action of luliberine on the Na+-K+)-ATPase activity is suggested."}
{"id": "PMID:218654", "title": "[Prostaglandin E binding by plasmatic membranes of thyroid gland cells].", "content": "The binding of prostaglandins E (PGE) with human and bovine thyrocyte plasmatic membranes was investigated by the new method with material from the kit for radioimmunoassay of PGE. There was a high affinity and a low affinity site for the specific PGE binding on human and bovine thyrocytes plasmic membranes. The effect of thyrotropin and cyclic nucleotides on the PGE binding by the membranes was revealed.", "contents": "[Prostaglandin E binding by plasmatic membranes of thyroid gland cells]. The binding of prostaglandins E (PGE) with human and bovine thyrocyte plasmatic membranes was investigated by the new method with material from the kit for radioimmunoassay of PGE. There was a high affinity and a low affinity site for the specific PGE binding on human and bovine thyrocytes plasmic membranes. The effect of thyrotropin and cyclic nucleotides on the PGE binding by the membranes was revealed."}
{"id": "PMID:218655", "title": "[Effect of 6N2'O-dibutyryl adenosine-3',5'-cyclomonophosphate on the protein synthesis of the subpharyngeal ganglia complex in the mollusk, Helix pomatia].", "content": "Proteins of the Helix pomatia abdominal complex were separated by electrophoresis. The electrophoretic mobility of most of the proteins was RF = 0.2--0.6. The abdominal ganglion was incubated in the medium with 1 = (4.5H3)-leucine and 2.10(-6) M 6N2'O-dibutyryladenosine-3',5'-cyclomonophosphate for 3, 6 and 24 hours. It was shown that radioactivity of specific low-mol wt neuronal proteins was increased by the former, but the latter inhibited this process.", "contents": "[Effect of 6N2'O-dibutyryl adenosine-3',5'-cyclomonophosphate on the protein synthesis of the subpharyngeal ganglia complex in the mollusk, Helix pomatia]. Proteins of the Helix pomatia abdominal complex were separated by electrophoresis. The electrophoretic mobility of most of the proteins was RF = 0.2--0.6. The abdominal ganglion was incubated in the medium with 1 = (4.5H3)-leucine and 2.10(-6) M 6N2'O-dibutyryladenosine-3',5'-cyclomonophosphate for 3, 6 and 24 hours. It was shown that radioactivity of specific low-mol wt neuronal proteins was increased by the former, but the latter inhibited this process."}
{"id": "PMID:218656", "title": "[Effect of radioprotectors on cAMP-dependent protein phosphorylation].", "content": "The capacity of radioprotectors (serotonin, aminoethylisothiuronium) to stimulate in radioprotective doses cAMP-dependent protein phosphorylation of the cytozol and nuclei of the mouse liver and of the spleen cytozol was shown in vivo. Radioprotectors were incapable of modulating in vitro the activity of protein kinases and the stimulating effect of cAMP. The data presented and previous investigations suggest that the activation of cAMP-dependent phosphorylation by radioprotectors was due to the increase of intracellular cAMP concentration under the effect of radioprotectors.", "contents": "[Effect of radioprotectors on cAMP-dependent protein phosphorylation]. The capacity of radioprotectors (serotonin, aminoethylisothiuronium) to stimulate in radioprotective doses cAMP-dependent protein phosphorylation of the cytozol and nuclei of the mouse liver and of the spleen cytozol was shown in vivo. Radioprotectors were incapable of modulating in vitro the activity of protein kinases and the stimulating effect of cAMP. The data presented and previous investigations suggest that the activation of cAMP-dependent phosphorylation by radioprotectors was due to the increase of intracellular cAMP concentration under the effect of radioprotectors."}
{"id": "PMID:218657", "title": "An inherited anomaly of human eosinophils and basophils.", "content": "Inclusions staining gray or blue-gray in Romanowsky treated films were found in eosinophils and basophils in a family as an autosomal dominant anomaly without overt clinical effects. Associated with the inclusions were distinctive crystals which were different from the crystalloids of eosinophil granules and from Charcot-Leyden crystals. The restriction of the anomaly to eosinophils and basophils indicates that these are related more closely to each other than to neutrophils and mast cells, and suggests the existence of a separate stem cell for eosinophils and basophils.", "contents": "An inherited anomaly of human eosinophils and basophils. Inclusions staining gray or blue-gray in Romanowsky treated films were found in eosinophils and basophils in a family as an autosomal dominant anomaly without overt clinical effects. Associated with the inclusions were distinctive crystals which were different from the crystalloids of eosinophil granules and from Charcot-Leyden crystals. The restriction of the anomaly to eosinophils and basophils indicates that these are related more closely to each other than to neutrophils and mast cells, and suggests the existence of a separate stem cell for eosinophils and basophils."}
{"id": "PMID:218658", "title": "Requirements of drug-induced endocytosis by intact human erythrocytes.", "content": "Study of drug-induced endocytosis in intact human erythrocytes continues to provide an opportunity for correlating membrane functions such as invagination and fusion with erythrocytic energetics and other determinants of plasma membrane function like Ca++. The studies reported indicate that high concentrations of vinblastine and chlorpromazine can produce endocytic vacuoles, albeit in reduced amounts, even in severely ATP depleted erythrocytes. In contrast, primaquine-induced endocytosis seems definitely dependent upon persistence of erythrocytic ATP stores. The ionophore mediated entry of Ca++ into erythrocytes potentiates primaquine endocytosis, inhibits vinblastine endocytosis, and has no regular effect on chlorpromazine endocytosis. Sodium lactate enhances primaquine endocytosis, probably by causing an increase in the entry of primaquine into erythrocytes. Cytochalasin B neither enhances nor inhibits erythrocytic endocytosis, thereby suggesting that microfibrils or analogues of microfibrils in erythrocytes are not involved in endocytosis. Cyclic nucleotide inhibition of endocytosis is confined to a very high concentration range of nucleotides in the medium. Primaquine and chlorpromazine endocytosis are inhibited by cyclic nucleotides as is vinblastine endocytosis.", "contents": "Requirements of drug-induced endocytosis by intact human erythrocytes. Study of drug-induced endocytosis in intact human erythrocytes continues to provide an opportunity for correlating membrane functions such as invagination and fusion with erythrocytic energetics and other determinants of plasma membrane function like Ca++. The studies reported indicate that high concentrations of vinblastine and chlorpromazine can produce endocytic vacuoles, albeit in reduced amounts, even in severely ATP depleted erythrocytes. In contrast, primaquine-induced endocytosis seems definitely dependent upon persistence of erythrocytic ATP stores. The ionophore mediated entry of Ca++ into erythrocytes potentiates primaquine endocytosis, inhibits vinblastine endocytosis, and has no regular effect on chlorpromazine endocytosis. Sodium lactate enhances primaquine endocytosis, probably by causing an increase in the entry of primaquine into erythrocytes. Cytochalasin B neither enhances nor inhibits erythrocytic endocytosis, thereby suggesting that microfibrils or analogues of microfibrils in erythrocytes are not involved in endocytosis. Cyclic nucleotide inhibition of endocytosis is confined to a very high concentration range of nucleotides in the medium. Primaquine and chlorpromazine endocytosis are inhibited by cyclic nucleotides as is vinblastine endocytosis."}
{"id": "PMID:218659", "title": "Potassium relaxation of vascular smooth muscle from spontaneously hypertensive rats.", "content": "Helical strips of tail artery from spontaneously hypertensive (SHR) and Kyoto Wistar normotensive rats (WKY) were observed to relax in response to potassium after contraction induced by norepinephrine in potassium-free solution. Helical strips from SHR consistently showed greater relaxation in response to the addition of potassium than did those from WKY. The amplitude of potassium-induced relaxation is believed to be an index of the activity of electrogenic sodium-potassium transport and hence of sodium-potassium ATPase. Thus, the sodium-potassium ATPase activity of SHR vascular smooth muscle is increased as compared to WKY. This interpretation is supported by the observation that ouabain eliminated potassium-induced relaxation in both SHR and WKY strips. Potassium-induced relaxation in SHR was more sensitive to ouabain inhibition than in WKY. Relaxation induced by potassium in SHR and WKY strips was also shown to vary with: (1) the length of incubation in potassium-free solution, and (2) the concentration of potassium added back. The results of these experiments on potassium-induced relaxation serve as evidence that SHR have either an increased intrinsic sodium-potassium ATPase activity, or an enzyme activity that has been stimulated to a greater degree by an elevated intracellular sodium concentration which resulted from the incubation in potassium-free solution.", "contents": "Potassium relaxation of vascular smooth muscle from spontaneously hypertensive rats. Helical strips of tail artery from spontaneously hypertensive (SHR) and Kyoto Wistar normotensive rats (WKY) were observed to relax in response to potassium after contraction induced by norepinephrine in potassium-free solution. Helical strips from SHR consistently showed greater relaxation in response to the addition of potassium than did those from WKY. The amplitude of potassium-induced relaxation is believed to be an index of the activity of electrogenic sodium-potassium transport and hence of sodium-potassium ATPase. Thus, the sodium-potassium ATPase activity of SHR vascular smooth muscle is increased as compared to WKY. This interpretation is supported by the observation that ouabain eliminated potassium-induced relaxation in both SHR and WKY strips. Potassium-induced relaxation in SHR was more sensitive to ouabain inhibition than in WKY. Relaxation induced by potassium in SHR and WKY strips was also shown to vary with: (1) the length of incubation in potassium-free solution, and (2) the concentration of potassium added back. The results of these experiments on potassium-induced relaxation serve as evidence that SHR have either an increased intrinsic sodium-potassium ATPase activity, or an enzyme activity that has been stimulated to a greater degree by an elevated intracellular sodium concentration which resulted from the incubation in potassium-free solution."}
{"id": "PMID:218660", "title": "Stimulation of resistance against local tumor growth, of hosts pretreated by combined local hyperthermia and X-irradiation.", "content": "The relationships involved in host resistance to tumor development were studied. Animals were pretreated by local hyperthermia, local irradiation and combined local hyperthermia and x-irradiation. After treatment, the animals were inoculated with tumor cells 0--96 or 0--120 hours post treatment. (BALB/c X C57B1/6)F1 mice were inoculated with the SV40 local fibrosarcoma, and (C3H/eB/B1)F1 mice were inoculated with the metastatic Lewis lung carcinoma. The results show an enhanced resistance to tumor development in animals pretreated by the combined simultaneous local heat and x-irradiation, as compared to animals only preirradiated, only preheated, or to control untreated tumor-bearing animals.", "contents": "Stimulation of resistance against local tumor growth, of hosts pretreated by combined local hyperthermia and X-irradiation. The relationships involved in host resistance to tumor development were studied. Animals were pretreated by local hyperthermia, local irradiation and combined local hyperthermia and x-irradiation. After treatment, the animals were inoculated with tumor cells 0--96 or 0--120 hours post treatment. (BALB/c X C57B1/6)F1 mice were inoculated with the SV40 local fibrosarcoma, and (C3H/eB/B1)F1 mice were inoculated with the metastatic Lewis lung carcinoma. The results show an enhanced resistance to tumor development in animals pretreated by the combined simultaneous local heat and x-irradiation, as compared to animals only preirradiated, only preheated, or to control untreated tumor-bearing animals."}
{"id": "PMID:218665", "title": "Recurrent facial fibrous histiocytoma.", "content": "A case of fibrous histiocytoma required 4 surgical excisions over an 11-year period. The technique of frequent observation and early excision of recurrences is probably the best approach to established histiocytomas. Complete primary excision seems to offer the best chance of definitive cure.", "contents": "Recurrent facial fibrous histiocytoma. A case of fibrous histiocytoma required 4 surgical excisions over an 11-year period. The technique of frequent observation and early excision of recurrences is probably the best approach to established histiocytomas. Complete primary excision seems to offer the best chance of definitive cure."}
{"id": "PMID:218666", "title": "Saturable adenosine 5'-triphosphate-independent binding of [3H]-ouabain to brain and cardiac tissue in vitro.", "content": "1. Several investigators have proposed that membrane Na+, K+-adenosine 5'-triphosphatase (Na+, K+-ATPase) is a mechanism for the transmembrane transport of cardiac glycosides, rather than the receptor for pharmacological actions of these agents. This implies that the glycosides bind to an intracellular constituent (receptor) other than Na+, K+-ATPase. 2. In search for such a receptor site, saturable ATP-independent [3H]-ouabain binding was studied in rat brain and dog and guinea-pig heart homogenates. The binding of the glucoside to this site results in a relatively unstable complex which is stabilized by K+ to a lesser extent than is the complex formed with the ATP-dependent binding to Na+, K+-ATPase. 3. The ATP-independent ouabain binding sites are more abundant in rat brain tissue than in cardiac tissue, and have a lower ouabain affinity compared to the binding sites on Na+, K+-ATPase. 4. These results do not support the contention that there are intracellular inotropic receptors for digitalis.", "contents": "Saturable adenosine 5'-triphosphate-independent binding of [3H]-ouabain to brain and cardiac tissue in vitro. 1. Several investigators have proposed that membrane Na+, K+-adenosine 5'-triphosphatase (Na+, K+-ATPase) is a mechanism for the transmembrane transport of cardiac glycosides, rather than the receptor for pharmacological actions of these agents. This implies that the glycosides bind to an intracellular constituent (receptor) other than Na+, K+-ATPase. 2. In search for such a receptor site, saturable ATP-independent [3H]-ouabain binding was studied in rat brain and dog and guinea-pig heart homogenates. The binding of the glucoside to this site results in a relatively unstable complex which is stabilized by K+ to a lesser extent than is the complex formed with the ATP-dependent binding to Na+, K+-ATPase. 3. The ATP-independent ouabain binding sites are more abundant in rat brain tissue than in cardiac tissue, and have a lower ouabain affinity compared to the binding sites on Na+, K+-ATPase. 4. These results do not support the contention that there are intracellular inotropic receptors for digitalis."}
{"id": "PMID:218667", "title": "Pharmacological aspects of neuromuscular transmission in the isolated diaphragm of the dystrophic (Rej 129) mouse.", "content": "1. Some aspects of the pharmacology of neuromuscular transmission have been studied in the isolated diaphragm of the normal and dystrophic mouse. 2. The effects of (+)-tubocurarine and atropine on the indirectly elicited twitch responses of the dystrophic diaphragm were indistinguishable from normal. 3. Intracellular recording techniques revealed no significant differences between the rise time, time to half decay, frequency and amplitude of miniature endplate potentials (m.e.p.ps) recorded in dystrophic muscle fibres, compared to those recorded in normal muscle fibres. 4. Transmitter null potential, the size of the available store of transmitter, the probability of release of the transmitter, and the characteristics of endplate potentials (e.p.ps) of dystrophic muscle fibres did not differ from normal. 5. The quantum contents of e.p.ps generated in response to nerve stimulation of 0.1 to 100 HZ were consistently larger in dystrophic muscle fibres than in normal muscle fibres, but the differences were not statistically significant under the conditions of the experiment.", "contents": "Pharmacological aspects of neuromuscular transmission in the isolated diaphragm of the dystrophic (Rej 129) mouse. 1. Some aspects of the pharmacology of neuromuscular transmission have been studied in the isolated diaphragm of the normal and dystrophic mouse. 2. The effects of (+)-tubocurarine and atropine on the indirectly elicited twitch responses of the dystrophic diaphragm were indistinguishable from normal. 3. Intracellular recording techniques revealed no significant differences between the rise time, time to half decay, frequency and amplitude of miniature endplate potentials (m.e.p.ps) recorded in dystrophic muscle fibres, compared to those recorded in normal muscle fibres. 4. Transmitter null potential, the size of the available store of transmitter, the probability of release of the transmitter, and the characteristics of endplate potentials (e.p.ps) of dystrophic muscle fibres did not differ from normal. 5. The quantum contents of e.p.ps generated in response to nerve stimulation of 0.1 to 100 HZ were consistently larger in dystrophic muscle fibres than in normal muscle fibres, but the differences were not statistically significant under the conditions of the experiment."}
{"id": "PMID:218668", "title": "Hyperpolarizing 'alpha 2'-adrenoceptors in rat sympathetic ganglia.", "content": "1 Receptors mediating catecholamine-induced hyperpolarization of isolated superior cervical sympathetic ganglia of the rat have been characterized by means of an extracellular recording method.2 (-)-Noradrenaline (EC(50), 1.7 +/- 0.6 muM) produced an immediate low-amplitude (< 400 muV) hyperpolarization. The hyperpolarization was increased on removal of external Ca(2+) or on reduction of external K(+) from 6 to 2 mM. Hyperpolarization was unaffected by changing the temperature from 25 degrees to 37 degrees C.3 Hyperpolarization was also produced by the following agonists (potencies relative to (-)-noradrenaline): (-)-noradrenaline 1; (+/-)-isoprenaline 0.41; (-)-phenylephrine 0.40; (+)-noradrenaline 0.13; 2-amino-6,7-dihydroxy tetrahydronaphthalene (ADTN) 0.25; dopamine 0.1; methoxamine 0.012; amidephrine 0.0015.4 Responses were antagonized by phentolamine (1 muM) but not by (+/-)-propranolol (1 muM), haloperidol (10 muM) or alpha-flupenthixol (1 muM). This suggested that hyperpolarization was mediated solely through alpha-receptor stimulation not through stimulation of beta-receptors or dopamine-receptors.5 Dose-ratio shifts produced by phentolamine varied with different agonists. The shift increased in inverse proportion to the ability of the agonists to inhibit [(3)H]-(-)-noradrenaline uptake, suggesting that uptake of agonists limited the dose-ratio shift. Cocaine and nortriptyline reduced catecholamine-induced hyperpolarization in concentrations (10 muM and 1 muM respectively) necessary to inhibit [(3)H]-(-)-noradrenaline uptake.6 Clonidine (0.01 to 1 muM), oxymetazoline (0.01 to 1 muM) and ergometrine (0.1 to 10 muM) produced a persistent, low-amplitude hyperpolarization, as though they were partial agonists. Responses to the agonists were blocked by yohimbine (1 muM) but not be prazosin (1 muM).7 It is concluded that the adrenergic cell bodies in the ganglion were hyperpolarized through activation of the same type of alpha-receptor (;alpha(2)-receptors') as those present at adrenergic nerve terminals.", "contents": "Hyperpolarizing 'alpha 2'-adrenoceptors in rat sympathetic ganglia. 1 Receptors mediating catecholamine-induced hyperpolarization of isolated superior cervical sympathetic ganglia of the rat have been characterized by means of an extracellular recording method.2 (-)-Noradrenaline (EC(50), 1.7 +/- 0.6 muM) produced an immediate low-amplitude (< 400 muV) hyperpolarization. The hyperpolarization was increased on removal of external Ca(2+) or on reduction of external K(+) from 6 to 2 mM. Hyperpolarization was unaffected by changing the temperature from 25 degrees to 37 degrees C.3 Hyperpolarization was also produced by the following agonists (potencies relative to (-)-noradrenaline): (-)-noradrenaline 1; (+/-)-isoprenaline 0.41; (-)-phenylephrine 0.40; (+)-noradrenaline 0.13; 2-amino-6,7-dihydroxy tetrahydronaphthalene (ADTN) 0.25; dopamine 0.1; methoxamine 0.012; amidephrine 0.0015.4 Responses were antagonized by phentolamine (1 muM) but not by (+/-)-propranolol (1 muM), haloperidol (10 muM) or alpha-flupenthixol (1 muM). This suggested that hyperpolarization was mediated solely through alpha-receptor stimulation not through stimulation of beta-receptors or dopamine-receptors.5 Dose-ratio shifts produced by phentolamine varied with different agonists. The shift increased in inverse proportion to the ability of the agonists to inhibit [(3)H]-(-)-noradrenaline uptake, suggesting that uptake of agonists limited the dose-ratio shift. Cocaine and nortriptyline reduced catecholamine-induced hyperpolarization in concentrations (10 muM and 1 muM respectively) necessary to inhibit [(3)H]-(-)-noradrenaline uptake.6 Clonidine (0.01 to 1 muM), oxymetazoline (0.01 to 1 muM) and ergometrine (0.1 to 10 muM) produced a persistent, low-amplitude hyperpolarization, as though they were partial agonists. Responses to the agonists were blocked by yohimbine (1 muM) but not be prazosin (1 muM).7 It is concluded that the adrenergic cell bodies in the ganglion were hyperpolarized through activation of the same type of alpha-receptor (;alpha(2)-receptors') as those present at adrenergic nerve terminals."}
{"id": "PMID:218669", "title": "Spontaneous rupture of a liver cell adenoma after long term methyltestosterone: report of a case successfully treated by emergency right hepatic lobectomy.", "content": "A case of spontaneous rupture of a liver cell adenoma is reported in a female transexual treated with methyltestosterone 150 mg daily for 7 years. Emergency right hepatic lobectomy was performed successfully. Histology showed peliosis hepatis also. Emergency resection of a liver cell adenoma has been reported in a young woman taking oral contraceptives, and an elective resection in another female transexual treated with methyltestosterone. However, to the best of our knowledge this is the first case of emergency resection of a spontaneously ruptured liver cell adenoma in a transexual treated with long term methyltestosterone. Since there are numerous other patients similarly treated, it may be expected that this complication will be seen again.", "contents": "Spontaneous rupture of a liver cell adenoma after long term methyltestosterone: report of a case successfully treated by emergency right hepatic lobectomy. A case of spontaneous rupture of a liver cell adenoma is reported in a female transexual treated with methyltestosterone 150 mg daily for 7 years. Emergency right hepatic lobectomy was performed successfully. Histology showed peliosis hepatis also. Emergency resection of a liver cell adenoma has been reported in a young woman taking oral contraceptives, and an elective resection in another female transexual treated with methyltestosterone. However, to the best of our knowledge this is the first case of emergency resection of a spontaneously ruptured liver cell adenoma in a transexual treated with long term methyltestosterone. Since there are numerous other patients similarly treated, it may be expected that this complication will be seen again."}
{"id": "PMID:218670", "title": "Mecillinam in enteric fever.", "content": "Twelve consecutive patients with enteric fever entered a trial of 14 days' treatment with mecillinam. Only three patients became afebrile within three days; four continued unimproved with fever and toxaemia for seven to nine days, when treatment was changed to chloramphenicol with good results. In one case the fever did not settle until the 13th day, and five days later the patient had a clinical relapse. Although all organisms recovered were fully sensitive to mecillinam, this drug is not an effective or consistent treatment for enteric fever.", "contents": "Mecillinam in enteric fever. Twelve consecutive patients with enteric fever entered a trial of 14 days' treatment with mecillinam. Only three patients became afebrile within three days; four continued unimproved with fever and toxaemia for seven to nine days, when treatment was changed to chloramphenicol with good results. In one case the fever did not settle until the 13th day, and five days later the patient had a clinical relapse. Although all organisms recovered were fully sensitive to mecillinam, this drug is not an effective or consistent treatment for enteric fever."}
{"id": "PMID:218671", "title": "Herpesvirus hominis antibodies among children and young adults in Ibadan.", "content": "A total of 422 sera collected from children and young adults living in Ibadan, Nigeria, has been examined for the presence of antibodies to type 1 and type 2 herpesvirus hominis. Type 1 antibodies were rapidly acquired from the age of 1 year onwards, reflecting the relatively poor living standards and the overcrowded accommodation among the population studied. Type 2 antibodies were acquired between the ages of 3 and 5 years. It is suggested that non-venereal spread of the virus must be responsible; prolonged survival of the virus on fomites, owing to the high environmental humidity, possibly accounts for this.", "contents": "Herpesvirus hominis antibodies among children and young adults in Ibadan. A total of 422 sera collected from children and young adults living in Ibadan, Nigeria, has been examined for the presence of antibodies to type 1 and type 2 herpesvirus hominis. Type 1 antibodies were rapidly acquired from the age of 1 year onwards, reflecting the relatively poor living standards and the overcrowded accommodation among the population studied. Type 2 antibodies were acquired between the ages of 3 and 5 years. It is suggested that non-venereal spread of the virus must be responsible; prolonged survival of the virus on fomites, owing to the high environmental humidity, possibly accounts for this."}
{"id": "PMID:218673", "title": "Hereditary sensory neuropathy with spastic paraplegia.", "content": "Five cases of spastic paraplegia with a progressive symmetrical sensory neuropathy producing ulceration and osteomyelitis of the hands and feet are reported. The pathology in one patient, who died of secondary amyloidosis, was similar to that found by Denny-Brown in hereditary sensory radicular neuropathy with severe loss of posterior root ganglion cells and loss of myelinated fibres in both peripheral nerves and posterior columns of the spinal cord. A sural nerve biopsy in another case showed a striking loss of both myelinated and unmyelinated fibres, with some evidence of degeneration and regeneration. The inheritance is probably by an autosomal recessive gene. The prognosis in the more severe form of the disorder is poor.", "contents": "Hereditary sensory neuropathy with spastic paraplegia. Five cases of spastic paraplegia with a progressive symmetrical sensory neuropathy producing ulceration and osteomyelitis of the hands and feet are reported. The pathology in one patient, who died of secondary amyloidosis, was similar to that found by Denny-Brown in hereditary sensory radicular neuropathy with severe loss of posterior root ganglion cells and loss of myelinated fibres in both peripheral nerves and posterior columns of the spinal cord. A sural nerve biopsy in another case showed a striking loss of both myelinated and unmyelinated fibres, with some evidence of degeneration and regeneration. The inheritance is probably by an autosomal recessive gene. The prognosis in the more severe form of the disorder is poor."}
{"id": "PMID:218674", "title": "Interaction of optic tract and visual wulst impulses on single units of the pigeon's optic tectum.", "content": "The influences of visual wulst and optic tract (OTr) stimulation on units recorded from the pigeon's optic tectum (OT) were studied. 127 tectal units were excited with short latency by a single OTr volley. Excitation was followed by a long-lasting inhibition. On 54 of the OTr-excited units, single-shock visual wulst stimulation exerted a long-lasting inhibitory effect. On 34 units, the effect was purely excitatory and, on 28 units, excitation was followed by prolonged inhibition. No effect was exerted by wulst stimulation on 24 units. These results are discussed in terms of convergence of wulst and retinal input on OT neurons, and the role of the integration of visual information from both peripheral and central origins is suggested for the OT neurons.", "contents": "Interaction of optic tract and visual wulst impulses on single units of the pigeon's optic tectum. The influences of visual wulst and optic tract (OTr) stimulation on units recorded from the pigeon's optic tectum (OT) were studied. 127 tectal units were excited with short latency by a single OTr volley. Excitation was followed by a long-lasting inhibition. On 54 of the OTr-excited units, single-shock visual wulst stimulation exerted a long-lasting inhibitory effect. On 34 units, the effect was purely excitatory and, on 28 units, excitation was followed by prolonged inhibition. No effect was exerted by wulst stimulation on 24 units. These results are discussed in terms of convergence of wulst and retinal input on OT neurons, and the role of the integration of visual information from both peripheral and central origins is suggested for the OT neurons."}
{"id": "PMID:218675", "title": "Wheel running sleep in two strains of mice: plasticity and rigidity in the expression of circadian rhythmicity.", "content": "The effects of 12--12 h, 6--6 h, 3--3 h and 1--1 h light--dark (L-D) cycles and of constant light (L--L) on wheel-running activity and electrograhically defined sleep were studied in two strains of mice, C57BL/6 and SEC/1Re. Wheel-running activity was inhibited by light and enhanced by darkness; however, in the C57 strain the L-D-induced changes were less pronounced and superimposed to a clear circadian rhythm. Under the L-L schedule clear patterns of daily rhythmicity were evident in the C57 strain but not in the SEC strain. Sleep was enhanced by light and inhibited by darkness. The L-D-induced changes of sleep were superimposed on the circadian rhythm in both strains; however, in the C57 strain these changes were larger in the circadian phase in which the animals were active. Under the L-L-schedule the C57 strain was characterized by more clear-cut patterns of daily rhythmicity than SEC mice. These phenomena are discussed in terms of plasticity of free-running rhythms of sleep and activity and of the genetic factors involved in the expression of circadian rhythmicity.", "contents": "Wheel running sleep in two strains of mice: plasticity and rigidity in the expression of circadian rhythmicity. The effects of 12--12 h, 6--6 h, 3--3 h and 1--1 h light--dark (L-D) cycles and of constant light (L--L) on wheel-running activity and electrograhically defined sleep were studied in two strains of mice, C57BL/6 and SEC/1Re. Wheel-running activity was inhibited by light and enhanced by darkness; however, in the C57 strain the L-D-induced changes were less pronounced and superimposed to a clear circadian rhythm. Under the L-L schedule clear patterns of daily rhythmicity were evident in the C57 strain but not in the SEC strain. Sleep was enhanced by light and inhibited by darkness. The L-D-induced changes of sleep were superimposed on the circadian rhythm in both strains; however, in the C57 strain these changes were larger in the circadian phase in which the animals were active. Under the L-L-schedule the C57 strain was characterized by more clear-cut patterns of daily rhythmicity than SEC mice. These phenomena are discussed in terms of plasticity of free-running rhythms of sleep and activity and of the genetic factors involved in the expression of circadian rhythmicity."}
{"id": "PMID:218676", "title": "Raphe unit activity in freely moving cats: correlation with level of behavioral arousal.", "content": "Dorsal raphe unit activity in freely moving cats showed a slow, rhythmic discharge rate during quiet waking (X=2.82 +/- 0.17 spikes/sec), and displayed a strong positive correlation with level of behavioral arousal. Presentation of an auditory stimulus during quiet waking resulted in significant increases in unit activity of 112% and 39% during the first sec and first 10 sec after the stimulus, respectively. This effect rapidly habituated with repeated stimulus presentations. During active waking, unit activity was significantly increased by 22% as compared to quiet waking, but there was no correlation between unit activity and gross body movements. Raphe unit activity showed a significant decrease of 17% during drowsiness (first appearance of EEG synchronization) as compared to quiet waking, and then progressive decreases during the early (--34%), middle (--52%) and late (--68%) phases of slow wave sleep. During all phases of slow wave sleep, the occurrence of sleep spindles was frequently associated with a transitory decrease in unit activity. The discharge rate would typically decrease during the few seconds immediately preceding the spindle, remains at this low level during the occurrence of the spindle, and then increase immediately after the spindle. Raphe unit activity showed decreases of 81% during pre-REM (the 60 sec immediately before REM onset) and 98% during REM, as compared to quiet waking. Unit activity reappeared 3.2 sec before the end of REM, with significant increases in unit activity of 83% and 17% during the first sec and first 10 sec of unit activity, respectively, as compared to quiet waking. The results of these studies are discussed in relation to the hypothesis that serotonin may play a modulatory, rather than mediative, role in behavioral and physiological processes.", "contents": "Raphe unit activity in freely moving cats: correlation with level of behavioral arousal. Dorsal raphe unit activity in freely moving cats showed a slow, rhythmic discharge rate during quiet waking (X=2.82 +/- 0.17 spikes/sec), and displayed a strong positive correlation with level of behavioral arousal. Presentation of an auditory stimulus during quiet waking resulted in significant increases in unit activity of 112% and 39% during the first sec and first 10 sec after the stimulus, respectively. This effect rapidly habituated with repeated stimulus presentations. During active waking, unit activity was significantly increased by 22% as compared to quiet waking, but there was no correlation between unit activity and gross body movements. Raphe unit activity showed a significant decrease of 17% during drowsiness (first appearance of EEG synchronization) as compared to quiet waking, and then progressive decreases during the early (--34%), middle (--52%) and late (--68%) phases of slow wave sleep. During all phases of slow wave sleep, the occurrence of sleep spindles was frequently associated with a transitory decrease in unit activity. The discharge rate would typically decrease during the few seconds immediately preceding the spindle, remains at this low level during the occurrence of the spindle, and then increase immediately after the spindle. Raphe unit activity showed decreases of 81% during pre-REM (the 60 sec immediately before REM onset) and 98% during REM, as compared to quiet waking. Unit activity reappeared 3.2 sec before the end of REM, with significant increases in unit activity of 83% and 17% during the first sec and first 10 sec of unit activity, respectively, as compared to quiet waking. The results of these studies are discussed in relation to the hypothesis that serotonin may play a modulatory, rather than mediative, role in behavioral and physiological processes."}
{"id": "PMID:218678", "title": "Mechanisms of augmented field potential responses in the rat olfactory bulb.", "content": "Olfactory bulb field potential and single unit responses to paired pulse stimulation of the lateral olfactory tract were observed in the rat. In agreement with previous reports, surgical levels of barbiturate anesthesia prolonged the period of diminution of the field potential responses to the test pulse relative to the effect seen under light anesthesia. Very deep barbiturate anesthesia (sufficient to depress the EEG) led to decreased responses to the primary pulse but augmented responses to the test pulse. Urethane and ether anesthesia produced augmented test responses without severely depressing the EEG and without producing a period of diminished test responses. Single unit recordings failed to show external plexiform layer units excited at the time of maximal augmentation of the field potential. Simultaneous single unit and field potential recordings showed that prolonged diminution of the field potential response was associated with prolonged suppression of unit responses to the test pulse, while augmented field potential responses were associated with decreased suppression of unit responses to the test pulse. These observations are most easily explained by the assumption of temporal facilitation in the synaptic output of mitral and tufted cells. This facilitation is masked by feedback inhibition under some conditions, particularly under barbiturate anesthesia.", "contents": "Mechanisms of augmented field potential responses in the rat olfactory bulb. Olfactory bulb field potential and single unit responses to paired pulse stimulation of the lateral olfactory tract were observed in the rat. In agreement with previous reports, surgical levels of barbiturate anesthesia prolonged the period of diminution of the field potential responses to the test pulse relative to the effect seen under light anesthesia. Very deep barbiturate anesthesia (sufficient to depress the EEG) led to decreased responses to the primary pulse but augmented responses to the test pulse. Urethane and ether anesthesia produced augmented test responses without severely depressing the EEG and without producing a period of diminished test responses. Single unit recordings failed to show external plexiform layer units excited at the time of maximal augmentation of the field potential. Simultaneous single unit and field potential recordings showed that prolonged diminution of the field potential response was associated with prolonged suppression of unit responses to the test pulse, while augmented field potential responses were associated with decreased suppression of unit responses to the test pulse. These observations are most easily explained by the assumption of temporal facilitation in the synaptic output of mitral and tufted cells. This facilitation is masked by feedback inhibition under some conditions, particularly under barbiturate anesthesia."}
{"id": "PMID:218679", "title": "An analysis of [3H]gamma-aminobutyric acid (GABA) binding in the human brain.", "content": "The binding of [3H]GABA to membranes prepared from human brains obtained post morten was examined. This binding was independent of patient sex, age (16--80 years), postmortem interval (4--33 h) or storage time when frozen (0-64 months). In preparations from cerebellar cortex various compounds displaced [3H]GABA binding with the following order of potency: muscimol greater than 3-aminopropanesulfonic acid greater than GABA greater than imidazoleacet acid greater than delta-amino-n-valeric acid greater than 3-hydroxyGABA greater than bicuculline. Other compounds active 'in vitro' included strychnine, homocarnosine and some (e.g. clozapine, thioridazine, pimozide) but not all (chlorpromazine, haloperiodol) neuroleptics. Compounds inactive 'in vitro' included aminooxyacetic acid, baclofen, picrotoxin, anticholinergics, metrazole, anticonvulsants and naloxone. Triton X-100 augmented the [3H]GABA binding (25 nM) by about 10--20-fold in most brain regions. [3H]GABA binding (IC50) was altered in Huntington's chorea and Reye's syndrome, but not in schizophrenics (4-neuroleptic-treated patients) or sudden infant death syndrome. The data presented strongly support the proposal that the measurement of [3H]GABA binding in postmortem human brain offers a reflection of the state of the physiologically relevant GABA receptor.", "contents": "An analysis of [3H]gamma-aminobutyric acid (GABA) binding in the human brain. The binding of [3H]GABA to membranes prepared from human brains obtained post morten was examined. This binding was independent of patient sex, age (16--80 years), postmortem interval (4--33 h) or storage time when frozen (0-64 months). In preparations from cerebellar cortex various compounds displaced [3H]GABA binding with the following order of potency: muscimol greater than 3-aminopropanesulfonic acid greater than GABA greater than imidazoleacet acid greater than delta-amino-n-valeric acid greater than 3-hydroxyGABA greater than bicuculline. Other compounds active 'in vitro' included strychnine, homocarnosine and some (e.g. clozapine, thioridazine, pimozide) but not all (chlorpromazine, haloperiodol) neuroleptics. Compounds inactive 'in vitro' included aminooxyacetic acid, baclofen, picrotoxin, anticholinergics, metrazole, anticonvulsants and naloxone. Triton X-100 augmented the [3H]GABA binding (25 nM) by about 10--20-fold in most brain regions. [3H]GABA binding (IC50) was altered in Huntington's chorea and Reye's syndrome, but not in schizophrenics (4-neuroleptic-treated patients) or sudden infant death syndrome. The data presented strongly support the proposal that the measurement of [3H]GABA binding in postmortem human brain offers a reflection of the state of the physiologically relevant GABA receptor."}
{"id": "PMID:218680", "title": "L9 modulation of L7's elicited gill withdrawal response in Aplysia.", "content": "The effects of induced L9 activity on gill motor neuron L7's ability to elicit a gill withdrawal response were studied. It was found that L9 was a modulator of L7's effectiveness to elicit gill movements. Following L9 activity, L7's ability to elicit a gill withdrawal response was significantly potentiated by up to 240% of control. L9 activity potentiated L7's elicited gill withdrawal response when frequencies of L7 activity were used which would result in decrement of the response or when frequencies were used in which decrement does not occur. Induced L9 activity may also have a minor potentiating effect on LDG1's ability to elicit gill movements. L9 was the only neuron found to possess these modulatory abilities. The interposition of the activity in the other gill motor neurons failed to have any effect. L9's modulatory role is separate and independent from its role as a gill motor neuron. L9's modulation of L7 is mediated peripherally in the gill and not in the CNS.", "contents": "L9 modulation of L7's elicited gill withdrawal response in Aplysia. The effects of induced L9 activity on gill motor neuron L7's ability to elicit a gill withdrawal response were studied. It was found that L9 was a modulator of L7's effectiveness to elicit gill movements. Following L9 activity, L7's ability to elicit a gill withdrawal response was significantly potentiated by up to 240% of control. L9 activity potentiated L7's elicited gill withdrawal response when frequencies of L7 activity were used which would result in decrement of the response or when frequencies were used in which decrement does not occur. Induced L9 activity may also have a minor potentiating effect on LDG1's ability to elicit gill movements. L9 was the only neuron found to possess these modulatory abilities. The interposition of the activity in the other gill motor neurons failed to have any effect. L9's modulatory role is separate and independent from its role as a gill motor neuron. L9's modulation of L7 is mediated peripherally in the gill and not in the CNS."}
{"id": "PMID:218681", "title": "Effects of median raphe nucleus lesions on hippocampal EEG in the freely moving rat.", "content": "The effects of median raphe lesions on the hippocampal EEG were examined in freely moving rats. First, median raphe lesions, including those restricted to the median raphe nucleus, unequivocally produced hippocampal low-frequency theta activity (5.8 Hz, SD = 0.47 Hz) during relaxed immobility which was not observed under normal conditions. This lesion-induced theta activity during immobiliy continued for at least 20 days, and was markedly suppressed by atropine sulfate (10 mg/kg, i.p.). On the other hand, reticular formation lesions had little effect on either hippocampal EEG patterns during immobility, movement or PS. Second, the mean frequency of theta activity was significantly reduced during movement and PS on the day following the median raphe lesion. These findings suggest a raphe-hippocampal pathway in which the median raphe mucleus plays a major role in hippocampal desynchronization (irregular pattern) by exerting an inhibitory influence on the hippocompal theta generating or facilitating mechanism. Thus the theta activity will be induced by the disinhibition following median raphe lesions.", "contents": "Effects of median raphe nucleus lesions on hippocampal EEG in the freely moving rat. The effects of median raphe lesions on the hippocampal EEG were examined in freely moving rats. First, median raphe lesions, including those restricted to the median raphe nucleus, unequivocally produced hippocampal low-frequency theta activity (5.8 Hz, SD = 0.47 Hz) during relaxed immobility which was not observed under normal conditions. This lesion-induced theta activity during immobiliy continued for at least 20 days, and was markedly suppressed by atropine sulfate (10 mg/kg, i.p.). On the other hand, reticular formation lesions had little effect on either hippocampal EEG patterns during immobility, movement or PS. Second, the mean frequency of theta activity was significantly reduced during movement and PS on the day following the median raphe lesion. These findings suggest a raphe-hippocampal pathway in which the median raphe mucleus plays a major role in hippocampal desynchronization (irregular pattern) by exerting an inhibitory influence on the hippocompal theta generating or facilitating mechanism. Thus the theta activity will be induced by the disinhibition following median raphe lesions."}
{"id": "PMID:218682", "title": "Specific versus non-specific actions of opioids on hippocampal neurones in the rat brain.", "content": "An investigation has been made into the pharmacological specificity of the actions of microelectrophoretically applied opioids on neurones in the rat hippocampus, a structure containing a low concentration of specific receptors for these substances. The majority of hippocampal neurones remained unaffected by morphine or enkephalin. Some neurones, however, displayed either inhibitory or excitatory responses to the opioids. Of the inhibitory effects, a few appeared to be specific, in that they could be antagonized by naloxone, but most of the other inhibitory responses were found to be potentiated by this drug. Similarly, naloxone not only failed to antagonize, but frequently potentiated the excitatory responses to the opioids. Further evidence for the predominantly non-specific nature of the responses of hippocampal neurones to opioids was provided by experiments with the stereoisomers levorphanol and dextrorphan. Neurones could be found which were either inhibited or excited by both enantiomers. Stereospecific responses, when observed, were inhibitory. Although non-specific, the excitatory effects of enkephalin and morphine on hippocampal neurones were greatly reduced in morphine tolerant/dependent rats. Indeed, in the hippocampus of these animals, the opioids had predominantly inhibitory effects which were potentiated, not antagonized, by naloxone. It is concluded that the low concentration of opiate receptors in the rat hippocampus renders neurones within this structure sensitive to a variety of nonspecific opioid actions.", "contents": "Specific versus non-specific actions of opioids on hippocampal neurones in the rat brain. An investigation has been made into the pharmacological specificity of the actions of microelectrophoretically applied opioids on neurones in the rat hippocampus, a structure containing a low concentration of specific receptors for these substances. The majority of hippocampal neurones remained unaffected by morphine or enkephalin. Some neurones, however, displayed either inhibitory or excitatory responses to the opioids. Of the inhibitory effects, a few appeared to be specific, in that they could be antagonized by naloxone, but most of the other inhibitory responses were found to be potentiated by this drug. Similarly, naloxone not only failed to antagonize, but frequently potentiated the excitatory responses to the opioids. Further evidence for the predominantly non-specific nature of the responses of hippocampal neurones to opioids was provided by experiments with the stereoisomers levorphanol and dextrorphan. Neurones could be found which were either inhibited or excited by both enantiomers. Stereospecific responses, when observed, were inhibitory. Although non-specific, the excitatory effects of enkephalin and morphine on hippocampal neurones were greatly reduced in morphine tolerant/dependent rats. Indeed, in the hippocampus of these animals, the opioids had predominantly inhibitory effects which were potentiated, not antagonized, by naloxone. It is concluded that the low concentration of opiate receptors in the rat hippocampus renders neurones within this structure sensitive to a variety of nonspecific opioid actions."}
{"id": "PMID:218684", "title": "Subcellular fractionation of rat cerebellum: separation of synaptosomal populations and heterogeneity of mitochondria.", "content": "A crude mitochondrial fraction (M) derived from manually disrupted cerebellar tissue and enriched in choline acetyltransferase (ChAT) activity was fractionated by centrifugation in discontinuous and continuous sucrose gradients. Further purification of 'cholinergic' synaptosomes was achieved (relative specific activity (RSA) of ChAT greater than 3), but the overlap with other synaptosomal populations was still considerable. Hand-homogenized cerebella processed through the full fractionation procedure described here and in previous papers yielded preparations enriched in certain neuronal structures and a fraction in which 'heavy' free mitochondria was concentrated. To characterize these preparations the activities of two transmitter enzymes (CHAT and glutamate decarboxylase, GAD) and 6 mitochondrial enzymes (succinate dehydrogenase (SDH), glutamate dehydrogenase (GDH), monoamine oxidase, citrate synthase, fumarase and GABA-aminotransferase) were determined. The distribution of the transmitter enzymes was clearly different in the preparations containing various neuronal structures. The GAD:ChAT RSA ratio was 2.4 for the glomerulus particles, 1.3 for the molecular layer fragments, 0.6 for the myelinated axon segments, and 0.2 for the 'cholinergic' synaptosomes. The mitochondrial enzyme profile of the preparations comprising mainly neuronal structures differed markedly from that of the 'free' mitochondrial fraction. Notably the latter was greatly enriched in GDH (RSA 5.6), whereas the SDH:GDH RSA ratio was relatively high in the former preparations. Nevertheless there were notable differences in the enzyme profile of the fractions of predominantly neuronal origin indicating that the enzyme composition of mitochondria of neuronal processes is not uniform.", "contents": "Subcellular fractionation of rat cerebellum: separation of synaptosomal populations and heterogeneity of mitochondria. A crude mitochondrial fraction (M) derived from manually disrupted cerebellar tissue and enriched in choline acetyltransferase (ChAT) activity was fractionated by centrifugation in discontinuous and continuous sucrose gradients. Further purification of 'cholinergic' synaptosomes was achieved (relative specific activity (RSA) of ChAT greater than 3), but the overlap with other synaptosomal populations was still considerable. Hand-homogenized cerebella processed through the full fractionation procedure described here and in previous papers yielded preparations enriched in certain neuronal structures and a fraction in which 'heavy' free mitochondria was concentrated. To characterize these preparations the activities of two transmitter enzymes (CHAT and glutamate decarboxylase, GAD) and 6 mitochondrial enzymes (succinate dehydrogenase (SDH), glutamate dehydrogenase (GDH), monoamine oxidase, citrate synthase, fumarase and GABA-aminotransferase) were determined. The distribution of the transmitter enzymes was clearly different in the preparations containing various neuronal structures. The GAD:ChAT RSA ratio was 2.4 for the glomerulus particles, 1.3 for the molecular layer fragments, 0.6 for the myelinated axon segments, and 0.2 for the 'cholinergic' synaptosomes. The mitochondrial enzyme profile of the preparations comprising mainly neuronal structures differed markedly from that of the 'free' mitochondrial fraction. Notably the latter was greatly enriched in GDH (RSA 5.6), whereas the SDH:GDH RSA ratio was relatively high in the former preparations. Nevertheless there were notable differences in the enzyme profile of the fractions of predominantly neuronal origin indicating that the enzyme composition of mitochondria of neuronal processes is not uniform."}
{"id": "PMID:218685", "title": "The effect of acidic amino acid antagonists on synaptic transmission in the hippocampal formation in vitro.", "content": "The effects on synaptic efficacy of the putative acidic amino acid antagonists, 2-amino-4-phosphonobutyric acid (APB), 2-amino-3-phosphonopropionic acid (APP), 1-hydroxy-3-amino-pyrrolidone-2 (HA-966) and glutamic acid diethyl ester (GDEE), were tested by bath application to the hippocampal slice preparation. On the basis of previous work, we hypothesized that APB, HA-966 and GDEE might antagonize synaptic responses to either glutamate or aspartate, but APP should antagonize only synaptic responses to aspartate. APB and HA-966 reduced the amplitude of the extracellular EPSP recorded during stimulation of the perforant path fibers, but APP and GDEE were without effect. APB, APP and HA-966, but not GDEE, consistently inhibited transmission at Schaffer collateral and commissural synapses. The mossy fiber evoked extracellular EPSP was unaffected by these agents. At the concentrations used in this study (usually 2.5 mM) none of these drugs affected the amplitude of presynaptic fiber potentials or antidromic responses, indicating that they probably acted at synapses. The spontaneous activity of hippocampal pyramidal cells, but not of dentate granule cells, increased in the presence of 2.5 mM APB. The amplitude of the population spike generated by Schaffer commissural stimulation initially increased following introduction of APB into the medium and then declined in parallel with the extracellular EPSP. In addition, APB reduced the duration of recurrent inhibition during the period when pyramidal cell firing was enhanced. These results can be explained by an antagonism at the synapse between pyramidal cell and inhibitory interneuron.", "contents": "The effect of acidic amino acid antagonists on synaptic transmission in the hippocampal formation in vitro. The effects on synaptic efficacy of the putative acidic amino acid antagonists, 2-amino-4-phosphonobutyric acid (APB), 2-amino-3-phosphonopropionic acid (APP), 1-hydroxy-3-amino-pyrrolidone-2 (HA-966) and glutamic acid diethyl ester (GDEE), were tested by bath application to the hippocampal slice preparation. On the basis of previous work, we hypothesized that APB, HA-966 and GDEE might antagonize synaptic responses to either glutamate or aspartate, but APP should antagonize only synaptic responses to aspartate. APB and HA-966 reduced the amplitude of the extracellular EPSP recorded during stimulation of the perforant path fibers, but APP and GDEE were without effect. APB, APP and HA-966, but not GDEE, consistently inhibited transmission at Schaffer collateral and commissural synapses. The mossy fiber evoked extracellular EPSP was unaffected by these agents. At the concentrations used in this study (usually 2.5 mM) none of these drugs affected the amplitude of presynaptic fiber potentials or antidromic responses, indicating that they probably acted at synapses. The spontaneous activity of hippocampal pyramidal cells, but not of dentate granule cells, increased in the presence of 2.5 mM APB. The amplitude of the population spike generated by Schaffer commissural stimulation initially increased following introduction of APB into the medium and then declined in parallel with the extracellular EPSP. In addition, APB reduced the duration of recurrent inhibition during the period when pyramidal cell firing was enhanced. These results can be explained by an antagonism at the synapse between pyramidal cell and inhibitory interneuron."}
{"id": "PMID:218686", "title": "The action of chlorpromazine at an isolated cholinergic synapse.", "content": "The effects of chlorpromazine (CPZ) on cholinergic transmission were studied at the isolated neuromuscular synapse of the frog. It was found that 5 x 10(-6) M CPZ produces the following effects: (1) a reduction in end-plate potential amplitude, mainly through inhibition of transmitter release at presynaptic nerve terminals; (2) a reduction in amplitude of focally recorded end-plate current without detectable change in nerve terminal potential: (3) a decrease in amplitude of miniature end-plate potentials; and (4) an increase in the frequency of spontaneous liberation of transmitter both in normal and calcium-free Ringer's solution. It is concluded that CPZ inhibits cholinergic transmission by a complex action on presynaptic and postsynaptic elements. The relation of these findings to central cholinergic activities of CPZ is discussed.", "contents": "The action of chlorpromazine at an isolated cholinergic synapse. The effects of chlorpromazine (CPZ) on cholinergic transmission were studied at the isolated neuromuscular synapse of the frog. It was found that 5 x 10(-6) M CPZ produces the following effects: (1) a reduction in end-plate potential amplitude, mainly through inhibition of transmitter release at presynaptic nerve terminals; (2) a reduction in amplitude of focally recorded end-plate current without detectable change in nerve terminal potential: (3) a decrease in amplitude of miniature end-plate potentials; and (4) an increase in the frequency of spontaneous liberation of transmitter both in normal and calcium-free Ringer's solution. It is concluded that CPZ inhibits cholinergic transmission by a complex action on presynaptic and postsynaptic elements. The relation of these findings to central cholinergic activities of CPZ is discussed."}
{"id": "PMID:218690", "title": "On the mechanism and site of action of enkephalin on single myenteric neurons.", "content": "Intracellular recordings were made from neurons in the isolated myenteric plexus of the guinea-pig ileum. Methionine- and leucine-enkephalin were applied to the neurons either by adding them to the perfusing solution in known concentrations or be ejecting them by microiontophoresis. When applied in the perfusion solution, the enkephalin (1 nM-1micron) hyperpolarized the soma membrane of less than half the neurons. The hyperpolarization was of rapid onset and reversed fully when the enkephalin was washed out; in a proportion of cells the hyperpolarization was associated with a fall in neuronal input resistance. This hyperpolarization was reversed or prevented by naloxone. When applied by iontophoresis to the soma membrane, enkephalin never hyperpolarized the myenteric neurons. Hyperpolarization in response to iontophoretic application of enkephalin was observed only when the enkephalin was applied to the surface of the ganglion away from the soma membrane; such hyperpolarization was prevented by addition of naloxone to the perfusion solution. The results indicate that the site at which enkephalin causes the naloxone-reversible hyperpolarization is not the soma membrane. The possibility is discussed that enkephalin may cuase presynaptic inhibition in this preparation by hyperpolarizing or increasing the conductance sites on the cellular processes from which acetylcholine is released.", "contents": "On the mechanism and site of action of enkephalin on single myenteric neurons. Intracellular recordings were made from neurons in the isolated myenteric plexus of the guinea-pig ileum. Methionine- and leucine-enkephalin were applied to the neurons either by adding them to the perfusing solution in known concentrations or be ejecting them by microiontophoresis. When applied in the perfusion solution, the enkephalin (1 nM-1micron) hyperpolarized the soma membrane of less than half the neurons. The hyperpolarization was of rapid onset and reversed fully when the enkephalin was washed out; in a proportion of cells the hyperpolarization was associated with a fall in neuronal input resistance. This hyperpolarization was reversed or prevented by naloxone. When applied by iontophoresis to the soma membrane, enkephalin never hyperpolarized the myenteric neurons. Hyperpolarization in response to iontophoretic application of enkephalin was observed only when the enkephalin was applied to the surface of the ganglion away from the soma membrane; such hyperpolarization was prevented by addition of naloxone to the perfusion solution. The results indicate that the site at which enkephalin causes the naloxone-reversible hyperpolarization is not the soma membrane. The possibility is discussed that enkephalin may cuase presynaptic inhibition in this preparation by hyperpolarizing or increasing the conductance sites on the cellular processes from which acetylcholine is released."}
{"id": "PMID:218691", "title": "Effect of K+ ions on kinetic properties of the (Na+, K+)-ATPase (EC 3.6.1.3) of bulk isolated glial cells, perikarya and synaptosomes from rabbit brain cortex.", "content": "Progress curves of the enzymatic reactions show that ATPases of bulk isolated glial cells, perikarya and synaptosomes exhibit hysteretic change. Initial velocities of enzyme activities were therefore obtained according to the equation valid for the hysteretic model. The (Na+, K+)-ATPase activities of the same brain fractions were measured before or after NaI treatment. Only glial and synaptosomal enzyme could be adequately extracted by using this procedure. Attempts to purify the (Na+, K+)-ATPase from brain perikarya by NaI extraction were unsuccessful. In order to determine the effect of the K+ ions on enzymic physiological efficiency (phys. eff.; i.e., the ratio Vmax/Kmapp) the variation of (Na+, K+)-ATPase activities from each brain fraction was measured as a function of Mg.ATP2- concentration in the presence of 5 and 20 mM K+ ions. High K+ ion concentrations (20 mM) increased the physiological efficiency of glial enzyme and decreased the same kinetic parameter in neuronal (perikaryal as well as synaptosomal) enzyme preparations. Results are discussed in relation to a possible distribution of distinct enzyme in different brain cell populations as well as a possible role of glial cells in an active regulation of K+ ion extracellular fluid in the CNS.", "contents": "Effect of K+ ions on kinetic properties of the (Na+, K+)-ATPase (EC 3.6.1.3) of bulk isolated glial cells, perikarya and synaptosomes from rabbit brain cortex. Progress curves of the enzymatic reactions show that ATPases of bulk isolated glial cells, perikarya and synaptosomes exhibit hysteretic change. Initial velocities of enzyme activities were therefore obtained according to the equation valid for the hysteretic model. The (Na+, K+)-ATPase activities of the same brain fractions were measured before or after NaI treatment. Only glial and synaptosomal enzyme could be adequately extracted by using this procedure. Attempts to purify the (Na+, K+)-ATPase from brain perikarya by NaI extraction were unsuccessful. In order to determine the effect of the K+ ions on enzymic physiological efficiency (phys. eff.; i.e., the ratio Vmax/Kmapp) the variation of (Na+, K+)-ATPase activities from each brain fraction was measured as a function of Mg.ATP2- concentration in the presence of 5 and 20 mM K+ ions. High K+ ion concentrations (20 mM) increased the physiological efficiency of glial enzyme and decreased the same kinetic parameter in neuronal (perikaryal as well as synaptosomal) enzyme preparations. Results are discussed in relation to a possible distribution of distinct enzyme in different brain cell populations as well as a possible role of glial cells in an active regulation of K+ ion extracellular fluid in the CNS."}
{"id": "PMID:218692", "title": "Maintained activity, excitation and inhibition of lateral geniculate neurons after monocular deafferentation in the adult cat.", "content": "Monocular deafferentation of the lateral geniculate nucleus (LGN) was accomplished by photocoagulation of the retinal vessels and the optic disc of one eye. Single cells with normal excitatory innervation from the intact eye (N-cells) and deafferented (D-) cells were recorded extracellularly with glass micropipettes from layers A and A1 of the LGN 10 days and 10 weeks after visual deafferentation. The maintained activity of D-cells was severely reduced after 10 days but had recovered significantly after 10 weeks. Different interspike interval distributions indicated a change in the main input source for the reactivated cells after 10 weeks. Stimulation of the intact retina with diffuse, high-intensity light flashes revealed missing or very small responses in the acutely deafferented cells. A still weak influence of the non-dominant eye on the deafferented cells after 10 days developed after 10 weeks into a biphasic response with an initial inhibitory period followed by a post-inhibitory exciation. Electrical stimulation of the optic chiasm revealed an increased inhibition during chronic deafferentation. Excitation following this inhibitory period was rare after 10 days but occurred frequently after 10 weeks. An enhanced excitability following stimulation of the visual cortex and the mesencephalic reticular formation was also observed after 10 weeks of deafferentation. An increased efficiency of all remaining inputs to the visually deafferented cells is concluded from the augmented inhibition and non-retinal excitation.", "contents": "Maintained activity, excitation and inhibition of lateral geniculate neurons after monocular deafferentation in the adult cat. Monocular deafferentation of the lateral geniculate nucleus (LGN) was accomplished by photocoagulation of the retinal vessels and the optic disc of one eye. Single cells with normal excitatory innervation from the intact eye (N-cells) and deafferented (D-) cells were recorded extracellularly with glass micropipettes from layers A and A1 of the LGN 10 days and 10 weeks after visual deafferentation. The maintained activity of D-cells was severely reduced after 10 days but had recovered significantly after 10 weeks. Different interspike interval distributions indicated a change in the main input source for the reactivated cells after 10 weeks. Stimulation of the intact retina with diffuse, high-intensity light flashes revealed missing or very small responses in the acutely deafferented cells. A still weak influence of the non-dominant eye on the deafferented cells after 10 days developed after 10 weeks into a biphasic response with an initial inhibitory period followed by a post-inhibitory exciation. Electrical stimulation of the optic chiasm revealed an increased inhibition during chronic deafferentation. Excitation following this inhibitory period was rare after 10 days but occurred frequently after 10 weeks. An enhanced excitability following stimulation of the visual cortex and the mesencephalic reticular formation was also observed after 10 weeks of deafferentation. An increased efficiency of all remaining inputs to the visually deafferented cells is concluded from the augmented inhibition and non-retinal excitation."}
{"id": "PMID:218693", "title": "Effects of substance P on neurones in the dorsal horn of the spinal cord of the cat.", "content": "The activity of single, physiologically identified neurones has been recorded both extra- and intracellularly in the 6th and 7th lumbar segments of the pentobarbitone-anaesthetized cat. In the majority of dorsal horn neurones studies (laminae 4 and 5 of Rexed) microiontophoretically applied synthetic substance P and the active fragment, substance P (4--11), were found to cause a slow and prolonged increase of the spontaneous firing rate and/or an enhancement of L-glutamate induced activity. Intracellular studies revealed that substance P caused a reversible depolarization of both dorsal horn neurones and motoneurones without a detectable alteration of the membrane resistance, antidromic action potential or postsynaptic potentials. These results are compatible with a possible role of substance P in sensory transmission in the spinal cord of the cat.", "contents": "Effects of substance P on neurones in the dorsal horn of the spinal cord of the cat. The activity of single, physiologically identified neurones has been recorded both extra- and intracellularly in the 6th and 7th lumbar segments of the pentobarbitone-anaesthetized cat. In the majority of dorsal horn neurones studies (laminae 4 and 5 of Rexed) microiontophoretically applied synthetic substance P and the active fragment, substance P (4--11), were found to cause a slow and prolonged increase of the spontaneous firing rate and/or an enhancement of L-glutamate induced activity. Intracellular studies revealed that substance P caused a reversible depolarization of both dorsal horn neurones and motoneurones without a detectable alteration of the membrane resistance, antidromic action potential or postsynaptic potentials. These results are compatible with a possible role of substance P in sensory transmission in the spinal cord of the cat."}
{"id": "PMID:218695", "title": "Noradrenergic transmission and female sexual behavior of guinea pigs.", "content": "Treatment with the dopamine beta-hydroxylase (DBH) inhibitor U-14,624 (50, 100, or 150 mg/kg) blocked the induction of lordosis behavior be estradiol benzoate (EB) and progesterone (P) in ovariectomized guinea pigs. After treatment with U-14,624 (100 mg/kg), norepinephrine (NE) content of medial basal hypothalamus, preoptic area and cortex was reduced (by 55%) and dopamine (DA) content of medial basal hypothalamus was increased (by 155%) during the period when females treated with EB and P normally display lordosis. Treatment with the NE receptor stimulator clonidine (1.0 mg/kg) restored lordosis behavior in females treated with EB, P, and U-14,624 (100 mg/kg), but the putative DA and serotonin (5-HT) receptor blockers pimozide (1.0 mg/kg) and methysergide (20.0 mg/kg) were ineffective in this respect. Thus, inhibition of lordosis after treatment with U-14,624 appeared to be attributable primarily to a reduction in NE neurotransmission, rather than to increase in DA or 5-HT activity. Because clonidine induced lordosis in females treated with EB, P, and U-14,624, it seemed unlikely that the facilitatory effects of clonidine on lordosis were mediated by activation of presynaptic alpha-adrenergic receptors (i.e. inhibitory NE autoreceptors) rather than by postsynaptic alpha-receptors. In addition, pretreatment with the postsynaptic alpha-adrenergic antagonist phenoxybenzamine (20.0 mg/kg) blocked the facilitation of lordosis by clonidine (1.0 mg/kg) in females primed with EB alone and with EB plus P. Thus, the facilitatory effects of clonidine on lordosis appear to be mediated by activation of postsynaptic alpha-adrenergic (i.e. NE) receptors. The results of this study provide further evidence that NE neurotransmission facilitates the expression of female sexual behavior in guinea pigs.", "contents": "Noradrenergic transmission and female sexual behavior of guinea pigs. Treatment with the dopamine beta-hydroxylase (DBH) inhibitor U-14,624 (50, 100, or 150 mg/kg) blocked the induction of lordosis behavior be estradiol benzoate (EB) and progesterone (P) in ovariectomized guinea pigs. After treatment with U-14,624 (100 mg/kg), norepinephrine (NE) content of medial basal hypothalamus, preoptic area and cortex was reduced (by 55%) and dopamine (DA) content of medial basal hypothalamus was increased (by 155%) during the period when females treated with EB and P normally display lordosis. Treatment with the NE receptor stimulator clonidine (1.0 mg/kg) restored lordosis behavior in females treated with EB, P, and U-14,624 (100 mg/kg), but the putative DA and serotonin (5-HT) receptor blockers pimozide (1.0 mg/kg) and methysergide (20.0 mg/kg) were ineffective in this respect. Thus, inhibition of lordosis after treatment with U-14,624 appeared to be attributable primarily to a reduction in NE neurotransmission, rather than to increase in DA or 5-HT activity. Because clonidine induced lordosis in females treated with EB, P, and U-14,624, it seemed unlikely that the facilitatory effects of clonidine on lordosis were mediated by activation of presynaptic alpha-adrenergic receptors (i.e. inhibitory NE autoreceptors) rather than by postsynaptic alpha-receptors. In addition, pretreatment with the postsynaptic alpha-adrenergic antagonist phenoxybenzamine (20.0 mg/kg) blocked the facilitation of lordosis by clonidine (1.0 mg/kg) in females primed with EB alone and with EB plus P. Thus, the facilitatory effects of clonidine on lordosis appear to be mediated by activation of postsynaptic alpha-adrenergic (i.e. NE) receptors. The results of this study provide further evidence that NE neurotransmission facilitates the expression of female sexual behavior in guinea pigs."}
{"id": "PMID:218700", "title": "[Effect of sodium n-dipropylacetate (sodium valproate) on GABA level of neuronal and glial cells in culture].", "content": "The effect of sodium n dipropylacetate (nDPA), a competitive GABA-T inhibitor with respect to GABA, has been investigated on glial and neuronal cellular GABA level. After 1 to 4 days incubation with nDPA in the culture medium, a decrease of GABA level in M5 neuroblastoma clonal cell lines and no modification of GABA level in C6 astrocytoma cells has been observed. The combined addition of nDPA 4 micrometer with dibutyryl cyclic AMP (1 mM) to the culture medium induces the same decrease in GABA level in C6 astrocytoma cells as the addition of DB-c-AMP alone. After shorter incubation time with nDPA (5-150 min), we observed a decreased GABA level in C6 astrocytoma glial cells.", "contents": "[Effect of sodium n-dipropylacetate (sodium valproate) on GABA level of neuronal and glial cells in culture]. The effect of sodium n dipropylacetate (nDPA), a competitive GABA-T inhibitor with respect to GABA, has been investigated on glial and neuronal cellular GABA level. After 1 to 4 days incubation with nDPA in the culture medium, a decrease of GABA level in M5 neuroblastoma clonal cell lines and no modification of GABA level in C6 astrocytoma cells has been observed. The combined addition of nDPA 4 micrometer with dibutyryl cyclic AMP (1 mM) to the culture medium induces the same decrease in GABA level in C6 astrocytoma cells as the addition of DB-c-AMP alone. After shorter incubation time with nDPA (5-150 min), we observed a decreased GABA level in C6 astrocytoma glial cells."}
{"id": "PMID:218701", "title": "[Effects of fasting and of ACTH on renal compensatory hypertrophy in the 48 hour uninephrectomized rat].", "content": "Renal compensatory hypertrophy (R.C.H.) is determined 48 h. after uninephrectomy in fed and fasting rats having free access to a NaCl solution. ACTH (18 gamma/100 g BW/d/2d) enhances R.C.H. in the fed animals. R.C.H. is severely impaired by food deprivation and the remaining kidney looses weight; a normal kidney weight can be maintained if the fasted, uninephrectomized rat is treated with ACTH. These experiments suggest that the stimulation of the adrenal cortex by ACTH has a renotrophic effect. This action may be related to the elevation of blood glucose or/and to the fall of the concentration of plasma K+.", "contents": "[Effects of fasting and of ACTH on renal compensatory hypertrophy in the 48 hour uninephrectomized rat]. Renal compensatory hypertrophy (R.C.H.) is determined 48 h. after uninephrectomy in fed and fasting rats having free access to a NaCl solution. ACTH (18 gamma/100 g BW/d/2d) enhances R.C.H. in the fed animals. R.C.H. is severely impaired by food deprivation and the remaining kidney looses weight; a normal kidney weight can be maintained if the fasted, uninephrectomized rat is treated with ACTH. These experiments suggest that the stimulation of the adrenal cortex by ACTH has a renotrophic effect. This action may be related to the elevation of blood glucose or/and to the fall of the concentration of plasma K+."}
{"id": "PMID:218702", "title": "[Proteasic polyseritis: effects of intraperitoneal injections of collagenase, alone or together with the administration of trypsin].", "content": "The authors showed previously that the effusions of the experimental polyseritis after intraperitoneal injections of trypsin and elastase, go from peritoneum to the pleural cavities and never from thorax to the peritoneum. The intraperitoneal injections of collagenase or of collagenase and trypsin can also cause polyseritis in the rat; but more often they provoke heavy hemorrhagic lesions of the wall of the abdomen and the diaphragm. Perforations of the diaphragm were observed in 8 rats of 32, with in 6, a intrathoracic hernia of the liver or the stomach. After the intrapleural injection of collagenase or of collagenase and trypsin, hemorrhagic lesions were seen in the thorax, but not in the abdomen. These facts are a new proof for the transdiaphragmatic propagation of the proteasic solutions injected in the peritoneum.", "contents": "[Proteasic polyseritis: effects of intraperitoneal injections of collagenase, alone or together with the administration of trypsin]. The authors showed previously that the effusions of the experimental polyseritis after intraperitoneal injections of trypsin and elastase, go from peritoneum to the pleural cavities and never from thorax to the peritoneum. The intraperitoneal injections of collagenase or of collagenase and trypsin can also cause polyseritis in the rat; but more often they provoke heavy hemorrhagic lesions of the wall of the abdomen and the diaphragm. Perforations of the diaphragm were observed in 8 rats of 32, with in 6, a intrathoracic hernia of the liver or the stomach. After the intrapleural injection of collagenase or of collagenase and trypsin, hemorrhagic lesions were seen in the thorax, but not in the abdomen. These facts are a new proof for the transdiaphragmatic propagation of the proteasic solutions injected in the peritoneum."}
{"id": "PMID:218703", "title": "[Modification of the response of nude mice to mouse hepatitis virus by transfer of heterozygote splenic cells].", "content": "The course of infection with low-virulence mouse hepatitis virus in nude mice was modified by transfer of sensitized or non-sensitized heterozygous spleen cells after the infection had been established. Infected nude mice having received the transfer of heterozygous spleen cells seem to have more severe signs of illness at early stage of infection than those without the heterozygous cell transfer, while they resisted against the infection.", "contents": "[Modification of the response of nude mice to mouse hepatitis virus by transfer of heterozygote splenic cells]. The course of infection with low-virulence mouse hepatitis virus in nude mice was modified by transfer of sensitized or non-sensitized heterozygous spleen cells after the infection had been established. Infected nude mice having received the transfer of heterozygous spleen cells seem to have more severe signs of illness at early stage of infection than those without the heterozygous cell transfer, while they resisted against the infection."}
{"id": "PMID:218705", "title": "Epidemiology of equine upper respiratory tract disease on standardbred racetracks.", "content": "The outbreaks of upper respiratory tract infections in horses at Standardbred racetracks were investigated over a three year period. The most serious epidemics of respiratory disease occurred in the winter and spring seasons. Both influenza viruses and equine herpesvirus 1 were shown to be present in the horse population. The herpesvirus was associated with respiratory disease particularly in the winter but the equine influenza viruses apparently were responsible for the major epidemics of respiratory disease at these tracks. Younger horses, two or three years of age, were particularly susceptible to upper respiratory disease and showed the greatest rate of seroconversion to influenza viruses. Major outbreaks of respiratory disease occurred when the proportion of young horses which had not previously been exposed to epidemics of respiratory disease reached 30 to 40% of the population at the track. Most horses over four years of age appeared to develop resistance to the infections.", "contents": "Epidemiology of equine upper respiratory tract disease on standardbred racetracks. The outbreaks of upper respiratory tract infections in horses at Standardbred racetracks were investigated over a three year period. The most serious epidemics of respiratory disease occurred in the winter and spring seasons. Both influenza viruses and equine herpesvirus 1 were shown to be present in the horse population. The herpesvirus was associated with respiratory disease particularly in the winter but the equine influenza viruses apparently were responsible for the major epidemics of respiratory disease at these tracks. Younger horses, two or three years of age, were particularly susceptible to upper respiratory disease and showed the greatest rate of seroconversion to influenza viruses. Major outbreaks of respiratory disease occurred when the proportion of young horses which had not previously been exposed to epidemics of respiratory disease reached 30 to 40% of the population at the track. Most horses over four years of age appeared to develop resistance to the infections."}
{"id": "PMID:218706", "title": "Experimental swine vesicular disease, pathology and immunofluorescence studies.", "content": "Two day old piglets were inoculated intravenously with 1 ml of swine vesicular disease virus UK-G 27-72 isolate. Using infectivity tests, immunofluorescent staining and gross and histopathological examination, pathogenesis of the infection was studied in tissue specimens collected daily from one through seven days postinoculation. Swine vesicular disease virus had a strong affinity for the epithelia of the tongue, snout, coronary band and lips, the myocardium and the lymphoid elements of the tonsil and the brain stem. The virus had the greatest affinity for the epithelium of the tongue. However, there was no evidence that the tongue was the initial replication site for swine vesicular disease virus. Prickle cells in the stratum spinosum appear to be the primary targets for the virus. The necrotic foci in the stratum spinosum appeared first, followed the next day by reticular degeneration and multilocular intraepidermal vesicular formation. In the digestive tract and most of the other visceral organs the short duration and sudden drop of the virus titres and the negative fluorescence and pathological findings suggest that these are not important sites for the replication of swine vesicular disease virus in this experiment. The virus was recovered from most of the central nervous tissue specimens. Although the piglets had significant central nervous system lesions, signs of impaired central nervous system function were not detected. However, subtle nervous signs could have been obscured by difficulties in locomotion resulting from severe lesions of the feet.", "contents": "Experimental swine vesicular disease, pathology and immunofluorescence studies. Two day old piglets were inoculated intravenously with 1 ml of swine vesicular disease virus UK-G 27-72 isolate. Using infectivity tests, immunofluorescent staining and gross and histopathological examination, pathogenesis of the infection was studied in tissue specimens collected daily from one through seven days postinoculation. Swine vesicular disease virus had a strong affinity for the epithelia of the tongue, snout, coronary band and lips, the myocardium and the lymphoid elements of the tonsil and the brain stem. The virus had the greatest affinity for the epithelium of the tongue. However, there was no evidence that the tongue was the initial replication site for swine vesicular disease virus. Prickle cells in the stratum spinosum appear to be the primary targets for the virus. The necrotic foci in the stratum spinosum appeared first, followed the next day by reticular degeneration and multilocular intraepidermal vesicular formation. In the digestive tract and most of the other visceral organs the short duration and sudden drop of the virus titres and the negative fluorescence and pathological findings suggest that these are not important sites for the replication of swine vesicular disease virus in this experiment. The virus was recovered from most of the central nervous tissue specimens. Although the piglets had significant central nervous system lesions, signs of impaired central nervous system function were not detected. However, subtle nervous signs could have been obscured by difficulties in locomotion resulting from severe lesions of the feet."}
{"id": "PMID:218707", "title": "Alteration in testicular cyclic AMP system in the rat following vasectomy.", "content": "Endogenous cyclic AMP levels and the activities of adenylate cyclase, cyclic AMP-dependent and independent protein kinases were examined in testes of mature rats bilaterally vasectomized for one, three and seven months. Although no significant alteration in testicular cyclic AMP was detected one month following vasectomy, marked decreases (by 55% and 32%, respectively) were seen three and seven months postvasectomy. Likewise, vasectomy also resulted in a significant decrease (by 25%) in the activity of testicular adenylate cyclase three and seven months after vasectomy. Although soluble cyclic AMP-dependent protein kinase activity remained unaffected three months postvasectomy, the activity of the cyclic nucleotide-dependent enzyme was significantly increased (by 21%) when compared to the sham-operated controls. Furthermore, while the protein kinase ratio (--cyclic AMP/+cyclic AMP) was decreased in animals vasectomized for three months, the ability of the enzyme to bind (3H) cyclic AMP in vitro was significantly enhanced (18%). Rats vasectomized for seven months showed similar biochemical alterations but the effects of this procedure were more pronounced. Moreover, while short-term vasectomy increased the responsiveness of seminiferous tubular adenylate cyclase to in vitro stimulation by follicle stimulating hormone, the activity of the enzyme was also increased (by 100%) in the presence of luteinizing hormone in vasectomized rats. These data raise the possibility that changes in testicular function seen following vasectomy may be related to the alterations in cyclic AMP metabolism as well as in the sensitivity of testicular adenylate cyclase to regulation by gonadotropins.", "contents": "Alteration in testicular cyclic AMP system in the rat following vasectomy. Endogenous cyclic AMP levels and the activities of adenylate cyclase, cyclic AMP-dependent and independent protein kinases were examined in testes of mature rats bilaterally vasectomized for one, three and seven months. Although no significant alteration in testicular cyclic AMP was detected one month following vasectomy, marked decreases (by 55% and 32%, respectively) were seen three and seven months postvasectomy. Likewise, vasectomy also resulted in a significant decrease (by 25%) in the activity of testicular adenylate cyclase three and seven months after vasectomy. Although soluble cyclic AMP-dependent protein kinase activity remained unaffected three months postvasectomy, the activity of the cyclic nucleotide-dependent enzyme was significantly increased (by 21%) when compared to the sham-operated controls. Furthermore, while the protein kinase ratio (--cyclic AMP/+cyclic AMP) was decreased in animals vasectomized for three months, the ability of the enzyme to bind (3H) cyclic AMP in vitro was significantly enhanced (18%). Rats vasectomized for seven months showed similar biochemical alterations but the effects of this procedure were more pronounced. Moreover, while short-term vasectomy increased the responsiveness of seminiferous tubular adenylate cyclase to in vitro stimulation by follicle stimulating hormone, the activity of the enzyme was also increased (by 100%) in the presence of luteinizing hormone in vasectomized rats. These data raise the possibility that changes in testicular function seen following vasectomy may be related to the alterations in cyclic AMP metabolism as well as in the sensitivity of testicular adenylate cyclase to regulation by gonadotropins."}
{"id": "PMID:218708", "title": "Comparison of results using electron microscope, immunodiffusion and fluorescent antibody analyses to detect rotavirus in diarrheic fecal samples of calves.", "content": "Seventy-nine diarrheic calf fecal samples were examined by electron microscopy, immunodiffusion and the fluorescent antibody technique for the presence of rotavirus (reovirus-like agent). Thirty-eight (48%) of the samples were positive by electron microscopy, 59% by immunodiffusion and 20% positive by fluorescent antibody technique analyses. Another 9% were suspect-positive by fluorescent antibody technique. Chymotrypsin treatment of the fecal samples increased the ease of observing the viral particles by electron microscopy and also intensified the immunodiffusion arcs obtained. Immunodiffusion analyses using specific antisera to the virus would appear to be a practical method of detecting rotavirus in diarrheic fecal samples.", "contents": "Comparison of results using electron microscope, immunodiffusion and fluorescent antibody analyses to detect rotavirus in diarrheic fecal samples of calves. Seventy-nine diarrheic calf fecal samples were examined by electron microscopy, immunodiffusion and the fluorescent antibody technique for the presence of rotavirus (reovirus-like agent). Thirty-eight (48%) of the samples were positive by electron microscopy, 59% by immunodiffusion and 20% positive by fluorescent antibody technique analyses. Another 9% were suspect-positive by fluorescent antibody technique. Chymotrypsin treatment of the fecal samples increased the ease of observing the viral particles by electron microscopy and also intensified the immunodiffusion arcs obtained. Immunodiffusion analyses using specific antisera to the virus would appear to be a practical method of detecting rotavirus in diarrheic fecal samples."}
{"id": "PMID:218709", "title": "The calf reo-like virus (rotavirus) vaccine: an ineffective immunization agent for rotaviral diarrhea of piglets.", "content": "Rotavirus, in a commercially available calf vaccine, did not replicate in newborn colostrum-free piglets inoculated orally with one half of a calf dose. Gross and microscopic examination of these vaccinated piglets revealed no lesions consistent with rotaviral infection and vaccinated piglets were susceptible to challenge by porcine rotavirus. Challenged piglets vomited, had diarrhea and became severely dehydrated. Rotavirus was visualized in their gut fluid. Villi in the small intestines were shortened, blunted and fused. Rotaviral antigens were seen in enterocytes.", "contents": "The calf reo-like virus (rotavirus) vaccine: an ineffective immunization agent for rotaviral diarrhea of piglets. Rotavirus, in a commercially available calf vaccine, did not replicate in newborn colostrum-free piglets inoculated orally with one half of a calf dose. Gross and microscopic examination of these vaccinated piglets revealed no lesions consistent with rotaviral infection and vaccinated piglets were susceptible to challenge by porcine rotavirus. Challenged piglets vomited, had diarrhea and became severely dehydrated. Rotavirus was visualized in their gut fluid. Villi in the small intestines were shortened, blunted and fused. Rotaviral antigens were seen in enterocytes."}
{"id": "PMID:218710", "title": "A comparative study of bovine herpesvirus 1247 and equine herpesvirus 1 in ponies.", "content": "The clinical and immunological response of ponies exposed to a bovine herpesvirus isolate and equine herpesvirus 1 were compared. Each virus was inoculated into two ponies by the intranasal route. One uninoculated pony was used with each group as a contact control. The four inoculated ponies developed a mild rhinitis with an increase in rectal temperature. Virus was recovered from nasal secretions collected from the four inoculated and one contact pony. All ponies developed a serum neutralizing antibody to each virus. The data show that the two viruses are similar.", "contents": "A comparative study of bovine herpesvirus 1247 and equine herpesvirus 1 in ponies. The clinical and immunological response of ponies exposed to a bovine herpesvirus isolate and equine herpesvirus 1 were compared. Each virus was inoculated into two ponies by the intranasal route. One uninoculated pony was used with each group as a contact control. The four inoculated ponies developed a mild rhinitis with an increase in rectal temperature. Virus was recovered from nasal secretions collected from the four inoculated and one contact pony. All ponies developed a serum neutralizing antibody to each virus. The data show that the two viruses are similar."}
{"id": "PMID:218711", "title": "Identification of enterotoxigenic Clostridium perfringens type A in mixed cultures.", "content": "Three known enterotoxigenic Clostridium perfringens type A strains were mixed in various combinations with three nonenterotoxigenic strains and three lots of animal intestinal contents. They were grown as mixed cultures and tested for the presence of enterotoxin by the fluorescent antibody, reversed passive hemagglutination and immunodiffusion techniques. The fluorescent antibody and reversed passive hemagglutination tests detected enterotoxin in all 16 cultures prepared but the immunodiffusion test failed on two cultures. Attempts to reisolate the enterotoxigenic strains from the mixed cultures was successful in 12 cases when two of five isolated colonies were selected.", "contents": "Identification of enterotoxigenic Clostridium perfringens type A in mixed cultures. Three known enterotoxigenic Clostridium perfringens type A strains were mixed in various combinations with three nonenterotoxigenic strains and three lots of animal intestinal contents. They were grown as mixed cultures and tested for the presence of enterotoxin by the fluorescent antibody, reversed passive hemagglutination and immunodiffusion techniques. The fluorescent antibody and reversed passive hemagglutination tests detected enterotoxin in all 16 cultures prepared but the immunodiffusion test failed on two cultures. Attempts to reisolate the enterotoxigenic strains from the mixed cultures was successful in 12 cases when two of five isolated colonies were selected."}
{"id": "PMID:218712", "title": "Cyclic nucleotides, cyclic nucleotide phosphodiesterase, and development in Myxococcus xanthus.", "content": "Exogenous cyclic nucleotide phosphodiesterase (PD) accelerated fruiting body (FB) formation and increased territory size of aggregates in Myxococcus xanthus. Both guanosine 3'5'-monophosphate (cGMP) and guanosine 5'-monophosphate (GMP) were antagonistic to the PD effect. Adenosine 3'5'-monophosphate (cAMP) increases FB numbers twofold in the absence but not in the presence of PD. PD induction is not affected by methionine or isoleucine, which inhibit, or by threonine, which stimulates, FB formation. There is an increase and subsequent decrease in cAMP levels during early glycerol-induced microcyst development but 10 mM theophylline or caffeine not only inhibited microcyst development but induced germination in the presence of glycerol. On the basis of these results and the reports of other investigators a tentative model is proposed based on a dual role for cyclic nucleotides in the development in M. xanthus.", "contents": "Cyclic nucleotides, cyclic nucleotide phosphodiesterase, and development in Myxococcus xanthus. Exogenous cyclic nucleotide phosphodiesterase (PD) accelerated fruiting body (FB) formation and increased territory size of aggregates in Myxococcus xanthus. Both guanosine 3'5'-monophosphate (cGMP) and guanosine 5'-monophosphate (GMP) were antagonistic to the PD effect. Adenosine 3'5'-monophosphate (cAMP) increases FB numbers twofold in the absence but not in the presence of PD. PD induction is not affected by methionine or isoleucine, which inhibit, or by threonine, which stimulates, FB formation. There is an increase and subsequent decrease in cAMP levels during early glycerol-induced microcyst development but 10 mM theophylline or caffeine not only inhibited microcyst development but induced germination in the presence of glycerol. On the basis of these results and the reports of other investigators a tentative model is proposed based on a dual role for cyclic nucleotides in the development in M. xanthus."}
{"id": "PMID:218714", "title": "Effect of serum-antigen incubation times on the expression of non-specific inhibitors of rubella hemagglutination.", "content": "Under certain conditions, serum very low-density lipoproteins (VLDL) and high-density lipoproteins (HDL) can inhibit rubella hemagglutination. The level of this non-specific hemagglutination-inhibition (HI) activity increases as the incubation period between serum and antigen is increased. Treatment of serum with heparin-MnCl2 does not precipitate HDL, and may not effect complete removal of all VLDL. This treatment method, therefore, should be considered a source of false-positive reactions, especially when extended serum-antigen incubation periods are used to enhance HI activity and to detect low levels of IgM.", "contents": "Effect of serum-antigen incubation times on the expression of non-specific inhibitors of rubella hemagglutination. Under certain conditions, serum very low-density lipoproteins (VLDL) and high-density lipoproteins (HDL) can inhibit rubella hemagglutination. The level of this non-specific hemagglutination-inhibition (HI) activity increases as the incubation period between serum and antigen is increased. Treatment of serum with heparin-MnCl2 does not precipitate HDL, and may not effect complete removal of all VLDL. This treatment method, therefore, should be considered a source of false-positive reactions, especially when extended serum-antigen incubation periods are used to enhance HI activity and to detect low levels of IgM."}
{"id": "PMID:218715", "title": "Studies of the microaerophilic nature of Campylobacter fetus subsp. jejuni. II. Role of exogenous superoxide anions and hydrogen peroxide.", "content": "The addition of bovine superoxide dismutase to Brucella broth or Brucellar agar greatly echanced the oxygen tolerance of Campylobacter fetus subsp. jejuni strain H840 (ATCC 29428). Catalase also enhanced oxygen tolerance, but to a lesser extent. These enzymes must act externally to the bacteria. All of the diverse compounds which enhance oxygen tolerance of C. fetus, including nor-epinephrine and a combination of ferrous sulfate, sodium metabisulfite, and sodium pyruvate, share the ability to quench either superoxide anions or hydrogen peroxide. On the basis of these and other data, we propose that C. fetus is more sensitive to exogenous superoxide anions and hydrogen peroxide than are aerotolerant bacteria, despite the occurrence of superoxide dismutase and catalse activities in C. fetus. Compounds that enhance oxygen tolerance in C. fetus appear to act by quenching superoxide anions and hydrogen peroxide which occur spontaneously in the culture medium.", "contents": "Studies of the microaerophilic nature of Campylobacter fetus subsp. jejuni. II. Role of exogenous superoxide anions and hydrogen peroxide. The addition of bovine superoxide dismutase to Brucella broth or Brucellar agar greatly echanced the oxygen tolerance of Campylobacter fetus subsp. jejuni strain H840 (ATCC 29428). Catalase also enhanced oxygen tolerance, but to a lesser extent. These enzymes must act externally to the bacteria. All of the diverse compounds which enhance oxygen tolerance of C. fetus, including nor-epinephrine and a combination of ferrous sulfate, sodium metabisulfite, and sodium pyruvate, share the ability to quench either superoxide anions or hydrogen peroxide. On the basis of these and other data, we propose that C. fetus is more sensitive to exogenous superoxide anions and hydrogen peroxide than are aerotolerant bacteria, despite the occurrence of superoxide dismutase and catalse activities in C. fetus. Compounds that enhance oxygen tolerance in C. fetus appear to act by quenching superoxide anions and hydrogen peroxide which occur spontaneously in the culture medium."}
{"id": "PMID:218718", "title": "Surgical treatment of tendosynovial sarcoma.", "content": "Tendosynovial sarcoma is notorious for its high rates of local recurrence and metastases after surgical treatment. A retrospective study was made of 109 cases of monobloc wide soft part resection and amputation for primary tumors, and 29 patients who underwent resection of pulmonary metastases. Actuarial five-year survival rates after soft part resection was 70% for untreated, and 61% for previously treated, locally recurrent neoplasms. Corresponding rates after amputation were 47% and 64%. Local tumor recurrence developed in 18% of the primary soft part resections and 4% of the amputations, usually when some basic surgical principle had been violated. 35% five-year survival was achieved with judicious resection of solitary and multiple lung metastases in most cases without chemotherapy. Local control of a tendosynovial sarcoma can be achieved with properly executed surgical procedures which adhere to established tenets of cancer surgery. Resection of pulmonary metastases merits an important position in the management of these patients.", "contents": "Surgical treatment of tendosynovial sarcoma. Tendosynovial sarcoma is notorious for its high rates of local recurrence and metastases after surgical treatment. A retrospective study was made of 109 cases of monobloc wide soft part resection and amputation for primary tumors, and 29 patients who underwent resection of pulmonary metastases. Actuarial five-year survival rates after soft part resection was 70% for untreated, and 61% for previously treated, locally recurrent neoplasms. Corresponding rates after amputation were 47% and 64%. Local tumor recurrence developed in 18% of the primary soft part resections and 4% of the amputations, usually when some basic surgical principle had been violated. 35% five-year survival was achieved with judicious resection of solitary and multiple lung metastases in most cases without chemotherapy. Local control of a tendosynovial sarcoma can be achieved with properly executed surgical procedures which adhere to established tenets of cancer surgery. Resection of pulmonary metastases merits an important position in the management of these patients."}
{"id": "PMID:218719", "title": "Cytotoxic drugs and the human adrenal cortex: a cell culture study.", "content": "Primary monolayer cultures of nonproliferating adult human adrenocortical cells have been used to screen 18 cytotoxic drugs used in cancer chemotherapy for direct effects on corticosteroidogenesis. None of the drugs tested, with the exception of 5-fluorouracil (5-FU) and its metabolite 5-fluorodeoxyuridine, showed significant activity at levels compatible with cortical cell viability and/or likely to be encountered during therapy. These two antimetabolites, however, resulted in a slow but long-lived reversible suppression of corticosteroidogenesis in both ACTH- and monobutyryl cyclic AMP-stimulated, as well as unstimulated cultures of human cells. Thus 10 micrograms/ml resulted in less than 80% inhibition after seven days treatment without any evidence of overt cytotoxicity. High-pressure liquid chromatography showed a suppression of all UV-absorbing steroids secreted. Examination of the ultrastructure of the treated cells showed significant changes in mitochondrial morphology, suggesting a possible site of action for the antisteroidogenic effects of 5-fluorouracil. These in vitro results suggest the possibility of adrenal suppression in vivo during long-term or high dose infusion 5-FU chemotherapy.", "contents": "Cytotoxic drugs and the human adrenal cortex: a cell culture study. Primary monolayer cultures of nonproliferating adult human adrenocortical cells have been used to screen 18 cytotoxic drugs used in cancer chemotherapy for direct effects on corticosteroidogenesis. None of the drugs tested, with the exception of 5-fluorouracil (5-FU) and its metabolite 5-fluorodeoxyuridine, showed significant activity at levels compatible with cortical cell viability and/or likely to be encountered during therapy. These two antimetabolites, however, resulted in a slow but long-lived reversible suppression of corticosteroidogenesis in both ACTH- and monobutyryl cyclic AMP-stimulated, as well as unstimulated cultures of human cells. Thus 10 micrograms/ml resulted in less than 80% inhibition after seven days treatment without any evidence of overt cytotoxicity. High-pressure liquid chromatography showed a suppression of all UV-absorbing steroids secreted. Examination of the ultrastructure of the treated cells showed significant changes in mitochondrial morphology, suggesting a possible site of action for the antisteroidogenic effects of 5-fluorouracil. These in vitro results suggest the possibility of adrenal suppression in vivo during long-term or high dose infusion 5-FU chemotherapy."}
{"id": "PMID:218720", "title": "Enhancement of biochemical transformation of mammalian cells by herpes simplex virus following nitrosomethylurea treatment.", "content": "A quantitative assay for the biochemical transformation of thymidine kinaseless mouse cells (N cIA cI10 cells) to an enzyme-positive phenotype by herpes simplex virus has been used to examine the effect of the carcinogen nitrosomethylurea on cell transformation. Exposure of cells to the chemical carcinogen, followed by virus infection, resulted in enhancement of transformation when compared to that seen with virus or chemical alone. Enhancement occurred after doses of nitrosomethylurea that were nontoxic to treated cells. A strong time dependence after treatment was demonstrated for enhancement which was correlated with the presence and excision-repair of alkylated DNA in treated cells.", "contents": "Enhancement of biochemical transformation of mammalian cells by herpes simplex virus following nitrosomethylurea treatment. A quantitative assay for the biochemical transformation of thymidine kinaseless mouse cells (N cIA cI10 cells) to an enzyme-positive phenotype by herpes simplex virus has been used to examine the effect of the carcinogen nitrosomethylurea on cell transformation. Exposure of cells to the chemical carcinogen, followed by virus infection, resulted in enhancement of transformation when compared to that seen with virus or chemical alone. Enhancement occurred after doses of nitrosomethylurea that were nontoxic to treated cells. A strong time dependence after treatment was demonstrated for enhancement which was correlated with the presence and excision-repair of alkylated DNA in treated cells."}
{"id": "PMID:218722", "title": "Humoral antibody response to bovine leukemia virus infection in cattle and sheep.", "content": "In this study, 345 cattle from 7 herds with a history of lymphosarcoma were tested for antibody to BLV antigens by three serological methods, namely immunodiffusion using a bovine leukemia virus glycoprotein with a molecular weight of 60,000 as antigen, and radioimmunoassay using a bovine leukemia virus glycoprotein with a molecular weight of 60,000 and a bovine leukemia virus protein with a molecular weight of 24,000 as antigen. The three tests under comparison agreed for 335 animals, 240 being negative in the three tests, and 95 being positive. Results were variable in ten cases only. Glycoprotein with a molecular weight of 60,000 antibody titers were systematically higher than were protein with a molecular weight of 24,000 antibody titers in bovine sera and milk, as well as in sera of experimentally infected sheep. In the latter case, antibodies to bovine leukemia virus antigens reached maximal values at the animal death in the tumor phase of the disease. Ratios of serum antiglycoprotein titer to milk titer varied between 4 and 117, showing that, if milk pools are to be used in surveys of bovine leukemia virus infection, use of very sensitive techniques of detection is mandatory.", "contents": "Humoral antibody response to bovine leukemia virus infection in cattle and sheep. In this study, 345 cattle from 7 herds with a history of lymphosarcoma were tested for antibody to BLV antigens by three serological methods, namely immunodiffusion using a bovine leukemia virus glycoprotein with a molecular weight of 60,000 as antigen, and radioimmunoassay using a bovine leukemia virus glycoprotein with a molecular weight of 60,000 and a bovine leukemia virus protein with a molecular weight of 24,000 as antigen. The three tests under comparison agreed for 335 animals, 240 being negative in the three tests, and 95 being positive. Results were variable in ten cases only. Glycoprotein with a molecular weight of 60,000 antibody titers were systematically higher than were protein with a molecular weight of 24,000 antibody titers in bovine sera and milk, as well as in sera of experimentally infected sheep. In the latter case, antibodies to bovine leukemia virus antigens reached maximal values at the animal death in the tumor phase of the disease. Ratios of serum antiglycoprotein titer to milk titer varied between 4 and 117, showing that, if milk pools are to be used in surveys of bovine leukemia virus infection, use of very sensitive techniques of detection is mandatory."}
{"id": "PMID:218725", "title": "Immunosuppressive properties of a virion polypeptide, a 15,000-dalton protein, from feline leukemia virus.", "content": "The 15,000-molecular-weight polypeptide (p15) of feline leukemia virus (FeLV) was shown to impair normal lymphocyte function in vitro and to abrogate immunity to feline oncornavirus disease in vivo. FeLVp15 suppressed concanavalin A-induced blast transformation of normal feline lymphocytes by 68%, while other virion proteins had no effect. p15 suppression was not due to toxicity, nor was p15 a competitive inhibitor of concanavalin A binding. Capping of receptors for concanavalin A on normal feline lymphocytes also was inhibited by either inactivated FeLV or FeLV p15. Groups of cats were immunized with either killed feline oncornavirus-associated cell membrane antigen bearing tumor cells or tumor cells plus FeLV p15. After challenge with feline sarcoma virus, three of four p15-treated cats developed progressive fatal fibrosarcoma as compared to one of five non-p15-treated cats. The cats receiving p15 also had lower cytotoxic antibody titers against feline oncornavirus-associated cell membrane antigen (mean peak titer, 1:6) than did the non-p15 group (1:74). These data support the hypothesis that the immunosuppression in cats infected with FeLV is mediated by FeLV p15.", "contents": "Immunosuppressive properties of a virion polypeptide, a 15,000-dalton protein, from feline leukemia virus. The 15,000-molecular-weight polypeptide (p15) of feline leukemia virus (FeLV) was shown to impair normal lymphocyte function in vitro and to abrogate immunity to feline oncornavirus disease in vivo. FeLVp15 suppressed concanavalin A-induced blast transformation of normal feline lymphocytes by 68%, while other virion proteins had no effect. p15 suppression was not due to toxicity, nor was p15 a competitive inhibitor of concanavalin A binding. Capping of receptors for concanavalin A on normal feline lymphocytes also was inhibited by either inactivated FeLV or FeLV p15. Groups of cats were immunized with either killed feline oncornavirus-associated cell membrane antigen bearing tumor cells or tumor cells plus FeLV p15. After challenge with feline sarcoma virus, three of four p15-treated cats developed progressive fatal fibrosarcoma as compared to one of five non-p15-treated cats. The cats receiving p15 also had lower cytotoxic antibody titers against feline oncornavirus-associated cell membrane antigen (mean peak titer, 1:6) than did the non-p15 group (1:74). These data support the hypothesis that the immunosuppression in cats infected with FeLV is mediated by FeLV p15."}
{"id": "PMID:218726", "title": "Mobility of lymphocyte surface membrane concanavalin A receptors of normal and feline leukemia virus-infected viremic felines.", "content": "The virus-associated depression of concanavalin A mitogenesis which accompanies feline leukemia virus-induced cat lymphoma was investigated by comparing lymphocyte surface receptor mobility of normal cats to that of viremic diseased animals. The mechanics of feline lymphocyte receptor mobility were studied using fluorescein-conjugated concanavalin A to quantitate lymphocyte capping. The results of a study of 21 disease-free animals showed that cat lymphocytes undergo appreciable concanavalin A capping, with a mean capping rate of 17% under conditions developed in this study. In contrast, morphologically normal peripheral blood lymphocytes of six feline leukemia virus-infected viremic cats, with or without lymphoma, exhibited a mean capping of only 7%, significantly less than that of the control animals (p less than 0.005). These findings suggest that a membrane-related lymphocyte deficiency accompanies the development of virus-induced lymphoma in the cat.", "contents": "Mobility of lymphocyte surface membrane concanavalin A receptors of normal and feline leukemia virus-infected viremic felines. The virus-associated depression of concanavalin A mitogenesis which accompanies feline leukemia virus-induced cat lymphoma was investigated by comparing lymphocyte surface receptor mobility of normal cats to that of viremic diseased animals. The mechanics of feline lymphocyte receptor mobility were studied using fluorescein-conjugated concanavalin A to quantitate lymphocyte capping. The results of a study of 21 disease-free animals showed that cat lymphocytes undergo appreciable concanavalin A capping, with a mean capping rate of 17% under conditions developed in this study. In contrast, morphologically normal peripheral blood lymphocytes of six feline leukemia virus-infected viremic cats, with or without lymphoma, exhibited a mean capping of only 7%, significantly less than that of the control animals (p less than 0.005). These findings suggest that a membrane-related lymphocyte deficiency accompanies the development of virus-induced lymphoma in the cat."}
{"id": "PMID:218727", "title": "Insulin and glucagon receptors in Morris hepatomas of varying growth rates.", "content": "The binding of both insulin and glucagon to receptors in plasma membranes from five hepatomas of varying growth rates was diminished when compared to plasma membranes from normal liver. Scatchard analyses of the binding data suggested that the decrease in glucagon binding was due to a decrease in binding capacity, whereas the decrease in insulin binding was due either to a decrease in binding affinity or to site-site interactions. The decreased binding of insulin, but not of glucagon, showed a significant correlation with increasing growth rate of the tumors. These data suggest, therefore, that decreased binding of insulin to receptors could be a feature of increasing growth rate in hepatomas.", "contents": "Insulin and glucagon receptors in Morris hepatomas of varying growth rates. The binding of both insulin and glucagon to receptors in plasma membranes from five hepatomas of varying growth rates was diminished when compared to plasma membranes from normal liver. Scatchard analyses of the binding data suggested that the decrease in glucagon binding was due to a decrease in binding capacity, whereas the decrease in insulin binding was due either to a decrease in binding affinity or to site-site interactions. The decreased binding of insulin, but not of glucagon, showed a significant correlation with increasing growth rate of the tumors. These data suggest, therefore, that decreased binding of insulin to receptors could be a feature of increasing growth rate in hepatomas."}
{"id": "PMID:218729", "title": "High incidence of mammary tumors in mice with inherited asplenia carriers for the nude gene.", "content": "A colony of mice suffering from dominant hemimelia associated with agenesis of the spleen has been developed and characterized during the past 7 years. The hereditarily asplenic (Dh/+) mice have a very low incidence (9%) of spontaneous mammary tumors (SMT). Asplenic (Dh/+) females were mated with mice homozygous (nu/nu) for hereditary athymia (nude) having a BALB/c background. BALB/c females heterozygous for the nu gene and with spleen (nu/+,+/+) have a moderate incidence (12%) of SMT, whereas nu/+,Dh/+ breeders have a drastic increase in the incidence of SMT to 46% when bred under identical conditions. Since all parent strains have a very low incidence of SMT, it appears that the spleen agenesis is a major factor accounting for an earlier and higher incidence of SMT in hereditarily asplenic (nu/+,Dh/+) mice than in normal (nu/+,+/+) siblings. The SMT express mammary tumor virus antigen(s) and possess estrogen, progesterone, and glucocorticoid receptors. The SMT rapidly metastasize and kill the host within 30 to 45 days. The BALB/c asplenic mice with SMT represent a unique model relevant to human breast cancer and for study of the function of the spleen in the development of solid tumors in general and of SMT in particular.", "contents": "High incidence of mammary tumors in mice with inherited asplenia carriers for the nude gene. A colony of mice suffering from dominant hemimelia associated with agenesis of the spleen has been developed and characterized during the past 7 years. The hereditarily asplenic (Dh/+) mice have a very low incidence (9%) of spontaneous mammary tumors (SMT). Asplenic (Dh/+) females were mated with mice homozygous (nu/nu) for hereditary athymia (nude) having a BALB/c background. BALB/c females heterozygous for the nu gene and with spleen (nu/+,+/+) have a moderate incidence (12%) of SMT, whereas nu/+,Dh/+ breeders have a drastic increase in the incidence of SMT to 46% when bred under identical conditions. Since all parent strains have a very low incidence of SMT, it appears that the spleen agenesis is a major factor accounting for an earlier and higher incidence of SMT in hereditarily asplenic (nu/+,Dh/+) mice than in normal (nu/+,+/+) siblings. The SMT express mammary tumor virus antigen(s) and possess estrogen, progesterone, and glucocorticoid receptors. The SMT rapidly metastasize and kill the host within 30 to 45 days. The BALB/c asplenic mice with SMT represent a unique model relevant to human breast cancer and for study of the function of the spleen in the development of solid tumors in general and of SMT in particular."}
{"id": "PMID:218730", "title": "Correlation of the induction of transcription of the AKR mouse genome 5-lododeoxyuridine with the activation of an endogenous murine leukemia virus.", "content": "5-iododeoxyuridine (IdUrd) is highly effective in inducing the production of endogenous viruses (e.g., RNA-containing murine leukemia virus) from a variety of cell lines that normally do not release such viruses. For the activation of murine leukemia virus by IdUrd, its incorporation into cellular DNA is necessary. We have explored the possibility that incorporated IdUrd qualitatively alters the transcription of cell DNA. Nucleic acid hybridization between radioactive mouse unique DNA and RNA from the highly activatable mouse AKR-2B cell line indicates that the normal extent of transcription in AKR-2B cells is considerably lower than that observed in other lines of mouse cells studied. Treatment of AKR-2B cells with IdUrd increases the extent of transcription of unique DNA by 60%, which corresponds to an induction of approximately 2.5 X 10(4) gene equivalents. Included among this new set of RNA's are sequences that are transcribed from the DNA genome of the endogenous AKR-type murine leukemia virus present in AKR-2B cells. IdUrd treatment also markedly increases the synthesis and/or the accumulation of those RNA transcripts which are normally expressed in untreated cells. These results suggest that IdUrd stimulates the overall transcription activity of AKR-2B cells. It is possible that IdUrd-induced activation of endogenous murine leukemia virus is a consequence of this stimulation.", "contents": "Correlation of the induction of transcription of the AKR mouse genome 5-lododeoxyuridine with the activation of an endogenous murine leukemia virus. 5-iododeoxyuridine (IdUrd) is highly effective in inducing the production of endogenous viruses (e.g., RNA-containing murine leukemia virus) from a variety of cell lines that normally do not release such viruses. For the activation of murine leukemia virus by IdUrd, its incorporation into cellular DNA is necessary. We have explored the possibility that incorporated IdUrd qualitatively alters the transcription of cell DNA. Nucleic acid hybridization between radioactive mouse unique DNA and RNA from the highly activatable mouse AKR-2B cell line indicates that the normal extent of transcription in AKR-2B cells is considerably lower than that observed in other lines of mouse cells studied. Treatment of AKR-2B cells with IdUrd increases the extent of transcription of unique DNA by 60%, which corresponds to an induction of approximately 2.5 X 10(4) gene equivalents. Included among this new set of RNA's are sequences that are transcribed from the DNA genome of the endogenous AKR-type murine leukemia virus present in AKR-2B cells. IdUrd treatment also markedly increases the synthesis and/or the accumulation of those RNA transcripts which are normally expressed in untreated cells. These results suggest that IdUrd stimulates the overall transcription activity of AKR-2B cells. It is possible that IdUrd-induced activation of endogenous murine leukemia virus is a consequence of this stimulation."}
{"id": "PMID:218731", "title": "Modulation of plasminogen activator synthesis in chick embryo fibroblasts by cyclic nucleotides and phorobol myristate acetate.", "content": "To explore the interaction of tumor promoters and sarcoma virus transformation with cellular regulatory mechanisms, we have studied induction of plasminogen activator synthesis by these agents in a background of changing cyclic nucleotide concentrations. We have confirmed the original report of Wigler and Weinstein (Nature, 259: 232, 1976) that phorbol-12-myristate-13-acetate (PMA), a potent tumor promoter, induces high levels of plasminogen activator production by chick embryo fibroblasts. Sarcoma virus transformation sensitizes the fibroblasts by lowering the threshold concentration for response to the action of PMA, and the effects of transformation and PMA on plasminogen activator synthesis are synergistic rather than additive. The plasminogen activators produced in the PMA-, virus-induced, or synergistically stimulated cultures are indistinguishable. Enzyme production in all three conditions is strongly but reversibly inhibited when cyclic nucleotide levels are raised by exposure to cyclic adenosine-3':5'-monophosphate or cholera toxin. A substantial fraction of the morphological effect that accompanies transformation is not affected by concentrations of cyclic nucleotides that suppress plasminogen activator production, and the two phenomena are therefore at least partially independent expressions of transformation in this system.", "contents": "Modulation of plasminogen activator synthesis in chick embryo fibroblasts by cyclic nucleotides and phorobol myristate acetate. To explore the interaction of tumor promoters and sarcoma virus transformation with cellular regulatory mechanisms, we have studied induction of plasminogen activator synthesis by these agents in a background of changing cyclic nucleotide concentrations. We have confirmed the original report of Wigler and Weinstein (Nature, 259: 232, 1976) that phorbol-12-myristate-13-acetate (PMA), a potent tumor promoter, induces high levels of plasminogen activator production by chick embryo fibroblasts. Sarcoma virus transformation sensitizes the fibroblasts by lowering the threshold concentration for response to the action of PMA, and the effects of transformation and PMA on plasminogen activator synthesis are synergistic rather than additive. The plasminogen activators produced in the PMA-, virus-induced, or synergistically stimulated cultures are indistinguishable. Enzyme production in all three conditions is strongly but reversibly inhibited when cyclic nucleotide levels are raised by exposure to cyclic adenosine-3':5'-monophosphate or cholera toxin. A substantial fraction of the morphological effect that accompanies transformation is not affected by concentrations of cyclic nucleotides that suppress plasminogen activator production, and the two phenomena are therefore at least partially independent expressions of transformation in this system."}
{"id": "PMID:218732", "title": "Decrease in collagen production in normal and Rous sarcoma virus-transformed chick embryo fibroblasts induced by phorbol myristate acetate.", "content": "The effect of the potent tumor promoter phorbol 12-myristate 13-acetate (PMA) on collagen synthesis, a differentiated property of chick embryo fibroblasts, was examined. Collagen synthesis, as measured by the rate of formation of [3H]hydroxyproline from [3H]proline, was found to be decreased in cells treated with PMA but not in cells treated with the parent alcohol phorbol. The decrease in collagenase-sensitive proteins was confirmed by polyacrylamide gel electrophoresis of cell lysates, indicating that the decrease could not be ascribed simply to an effect on prolyl hydroxylase. Although a decrease in collagen synthesis was observed after one day, five days were required for a maximal reduction to 20% of that of dimethyl sulfoxide-treated controls. The effect of PMA on collagen synthesis was reversible. It was therefore not the result of a permanent transformation of the cells or of the selection of a population of cells with a reduced capacity for collagen synthesis. Collagen synthesis was decreased in chick embryo fibroblasts transformed by Rous sarcoma virus. Treatment of these cells with PMA for 5 days brought about a further decrease to 50% of the level in dimethyl sulfoxide-treated transformed controls.", "contents": "Decrease in collagen production in normal and Rous sarcoma virus-transformed chick embryo fibroblasts induced by phorbol myristate acetate. The effect of the potent tumor promoter phorbol 12-myristate 13-acetate (PMA) on collagen synthesis, a differentiated property of chick embryo fibroblasts, was examined. Collagen synthesis, as measured by the rate of formation of [3H]hydroxyproline from [3H]proline, was found to be decreased in cells treated with PMA but not in cells treated with the parent alcohol phorbol. The decrease in collagenase-sensitive proteins was confirmed by polyacrylamide gel electrophoresis of cell lysates, indicating that the decrease could not be ascribed simply to an effect on prolyl hydroxylase. Although a decrease in collagen synthesis was observed after one day, five days were required for a maximal reduction to 20% of that of dimethyl sulfoxide-treated controls. The effect of PMA on collagen synthesis was reversible. It was therefore not the result of a permanent transformation of the cells or of the selection of a population of cells with a reduced capacity for collagen synthesis. Collagen synthesis was decreased in chick embryo fibroblasts transformed by Rous sarcoma virus. Treatment of these cells with PMA for 5 days brought about a further decrease to 50% of the level in dimethyl sulfoxide-treated transformed controls."}
{"id": "PMID:218734", "title": "Virus particles in the basal plate of rhesus monkey and baboon placenta.", "content": "C-type virus particles and particles, approximately 35 nm in diameter, were present in the region of the basal plate from the placenta of a rhesus monkey and two baboons. Both particles appeared to bud from the plasma membrane of the cytotrophoblast: large, pleomorphic cells with cytoplasmic extensions, indented nuclei, well-developed endoplasmic reticulum, and glycogen deposits. Extracellular particles were enmeshed within a fibrous matrix. Particles were also observed in the junctional zone, but not in the decidua. C-type virus particles from the rhesus monkey and baboons differed in ultrastructure from each other and from C-type mouse leukemia virus particles. The 35-nm-type particle was spherical with a dense central core.", "contents": "Virus particles in the basal plate of rhesus monkey and baboon placenta. C-type virus particles and particles, approximately 35 nm in diameter, were present in the region of the basal plate from the placenta of a rhesus monkey and two baboons. Both particles appeared to bud from the plasma membrane of the cytotrophoblast: large, pleomorphic cells with cytoplasmic extensions, indented nuclei, well-developed endoplasmic reticulum, and glycogen deposits. Extracellular particles were enmeshed within a fibrous matrix. Particles were also observed in the junctional zone, but not in the decidua. C-type virus particles from the rhesus monkey and baboons differed in ultrastructure from each other and from C-type mouse leukemia virus particles. The 35-nm-type particle was spherical with a dense central core."}
{"id": "PMID:218735", "title": "Thymidine and hypoxanthine requirements for the proliferation of normal and Rous sarcoma virus-infected chicken fibroblasts in the presence of methotrexate.", "content": "Cultured normal and Rous sarcoma virus-infected chicken fibroblasts do not differ in the concentrations of thymidine or of hypoxanthine that they require to proliferate in the presence of a methotrexate block. For maximal proliferation, thymidine is required at 10(-6) M, while hypoxanthine is required at 10(-5) M. The normal and Rous-infected fibroblasts show very similar, if not identical, decreases in proliferation rates at suboptimal concentrations of thymidine or hypoxanthine. These results suggest that conversion of fibroblasts to the neoplastic state does not alter their capacity to salvage thymidine or purines from the extracellular fluid or to metabolize these compounds.", "contents": "Thymidine and hypoxanthine requirements for the proliferation of normal and Rous sarcoma virus-infected chicken fibroblasts in the presence of methotrexate. Cultured normal and Rous sarcoma virus-infected chicken fibroblasts do not differ in the concentrations of thymidine or of hypoxanthine that they require to proliferate in the presence of a methotrexate block. For maximal proliferation, thymidine is required at 10(-6) M, while hypoxanthine is required at 10(-5) M. The normal and Rous-infected fibroblasts show very similar, if not identical, decreases in proliferation rates at suboptimal concentrations of thymidine or hypoxanthine. These results suggest that conversion of fibroblasts to the neoplastic state does not alter their capacity to salvage thymidine or purines from the extracellular fluid or to metabolize these compounds."}
{"id": "PMID:218736", "title": "Patterns of relapse in patients with small cell carcinoma of the lung treated with adriamycin-cyclophosphamide chemotherapy and radiation therapy.", "content": "Twenty-seven patients with small cell carcinoma of the lung were treated sequentially with induction chemotherapy (adriamycin and cyclophosphamide), radiation therapy (chest and whole-brain), and then maintenance chemotherapy for 2 years. Twenty responding patients were followed to relapse and patterns of recurrence were observed. This combined treatment resulted in a complete remission rate of 80% and a median survival of 565 days in limited-disease patients. Relapse overwhelmingly occurred in the chest, but patients receiving higher-dose radiation (4000-4500 rads in split-course) had a significant prolongation of time to recurrence compared to patients receiving 3000 rads in a single course of radiation (540 versus 270 days). Despite a long mean survival, only one limited-disease patient relapsed outside of the brain or chest, suggesting that chemotherapy had a good protective effect against micrometastatic disease. Three patients relapsed in the brain at 330, 450, and 520 days, suggesting that in future studies the prophylactic whole-brain radiation (3000 rads) should be intensified.", "contents": "Patterns of relapse in patients with small cell carcinoma of the lung treated with adriamycin-cyclophosphamide chemotherapy and radiation therapy. Twenty-seven patients with small cell carcinoma of the lung were treated sequentially with induction chemotherapy (adriamycin and cyclophosphamide), radiation therapy (chest and whole-brain), and then maintenance chemotherapy for 2 years. Twenty responding patients were followed to relapse and patterns of recurrence were observed. This combined treatment resulted in a complete remission rate of 80% and a median survival of 565 days in limited-disease patients. Relapse overwhelmingly occurred in the chest, but patients receiving higher-dose radiation (4000-4500 rads in split-course) had a significant prolongation of time to recurrence compared to patients receiving 3000 rads in a single course of radiation (540 versus 270 days). Despite a long mean survival, only one limited-disease patient relapsed outside of the brain or chest, suggesting that chemotherapy had a good protective effect against micrometastatic disease. Three patients relapsed in the brain at 330, 450, and 520 days, suggesting that in future studies the prophylactic whole-brain radiation (3000 rads) should be intensified."}
{"id": "PMID:218737", "title": "Action of 2-acetamido-2-deoxy-beta-D-hexosidase from Turbo cornutus on periodate-oxidized and Smith-degraded, blood-group HLeb and Lea substances from human, ovarian-cyst fluids.", "content": "Immunochemical and chemical studies were used to monitor and evaluate the structural changes produced by an enzyme from Turbo cornutus in periodate-oxidized and Smith-degraded, human blood-group substances from ovarian cysts. After the first step of periodate oxidation and Smith degradation, two blood-group substances, JS (HLeb and N-1 (Lea), were precipitated by mouse-myeloma S117 serum, specific for terminal, nonreducing, beta-D-linked 2-acetamido-2-deoxy-D-glucosyl groups, but not by type XIV antipneumococcal horse serum specific for terminal, nonreducing, beta-D-linked D-galactosyl groups. An exoglycosidase, 2-acetamido-2-deoxy-beta-D-hexosidase (beta-N-acetylhexosaminidase) from Turbo cornutus, split off 2-acetamido-2-deoxy-D-glucose amounting to 22.5 and 20.4% of the total weight of JS and N-1 blood-group substances, respectively. After enzymic digestion, both blood-group substances precipitated with type XIV serum, and did not precipitate with S117 serum. The findings are in agreement with the structure propsed for the water-soluble, blood-group substances [Lloyd and Kabat, Proc. Natl. Acad. Sci. U.S.A., 61 (1968) 1477]. Specific enzymes can be of value in structural studies when used in conjunction with sequential periodate oxidation and Smith degradation.", "contents": "Action of 2-acetamido-2-deoxy-beta-D-hexosidase from Turbo cornutus on periodate-oxidized and Smith-degraded, blood-group HLeb and Lea substances from human, ovarian-cyst fluids. Immunochemical and chemical studies were used to monitor and evaluate the structural changes produced by an enzyme from Turbo cornutus in periodate-oxidized and Smith-degraded, human blood-group substances from ovarian cysts. After the first step of periodate oxidation and Smith degradation, two blood-group substances, JS (HLeb and N-1 (Lea), were precipitated by mouse-myeloma S117 serum, specific for terminal, nonreducing, beta-D-linked 2-acetamido-2-deoxy-D-glucosyl groups, but not by type XIV antipneumococcal horse serum specific for terminal, nonreducing, beta-D-linked D-galactosyl groups. An exoglycosidase, 2-acetamido-2-deoxy-beta-D-hexosidase (beta-N-acetylhexosaminidase) from Turbo cornutus, split off 2-acetamido-2-deoxy-D-glucose amounting to 22.5 and 20.4% of the total weight of JS and N-1 blood-group substances, respectively. After enzymic digestion, both blood-group substances precipitated with type XIV serum, and did not precipitate with S117 serum. The findings are in agreement with the structure propsed for the water-soluble, blood-group substances [Lloyd and Kabat, Proc. Natl. Acad. Sci. U.S.A., 61 (1968) 1477]. Specific enzymes can be of value in structural studies when used in conjunction with sequential periodate oxidation and Smith degradation."}
{"id": "PMID:218742", "title": "The effect of DDT on vitamin D metabolism and calcium binding activity in the chick.", "content": "The mechanism of DDT impaired calcium absorption was studied in control, DDT fed and starved chicks. The metabolism of [3H]cholecalciferol was the same in the 3 groups, but the DDT fed and starved chicks had less intestinal calcium binding activity than the control chicks. These results suggest that DDT impaired calcium absorption and intestinal calcium binding activity may be a result of DDT induced anorexia.", "contents": "The effect of DDT on vitamin D metabolism and calcium binding activity in the chick. The mechanism of DDT impaired calcium absorption was studied in control, DDT fed and starved chicks. The metabolism of [3H]cholecalciferol was the same in the 3 groups, but the DDT fed and starved chicks had less intestinal calcium binding activity than the control chicks. These results suggest that DDT impaired calcium absorption and intestinal calcium binding activity may be a result of DDT induced anorexia."}
{"id": "PMID:218743", "title": "Studies on the nephrotoxicity of p-nitrophenylarsonic acid: changes in rat kidney and urinary enzyme activities following the administration of p-nitrophenylarsonic acid.", "content": "Histological studies showed that the administration of p-nitrophenylarsonic acid to rats resulted in renal tubular necrosis. The nephrotoxin was administered intraperitoneally and doses greater than 30 mg/kg were found to be fatal. The severity of the renal lesion depended on the amount of the nephrotoxin used. Elevated serum urea levels, urinary protein and volume were recorded over an 8-day period following the injection of the nephrotoxin. These changes were paralleled by an increase in the activity of lactate dehydrogenase, acid and alkaline phosphatase, N-acetyl-beta-glucosaminidase and beta-glucosidase in the urine. beta-Glycosidase activities increased in kidney homogenates, immediately after the injection of the nephrotoxin, but this eventually fell to well below the normal range. Subcellular fractions were prepared from sucrose homogenates by differential centrifugation and beta-glycosidases and cytochrome oxidase were used as enzyme markers. Only minor changes in the activity of cytochrome oxidase activity resulted from the administration of p-nitrophenylarsonic acid. One of the earliest indications of renal damage was a decrease in lysosomal latency. The activities of the lysosomal and soluble enzymes were elevated above normal during the first two days after the injection of p-nitrophenylarsonic acid, but they fell to values, significantly lower than normal, on the third day. The isoenzymic forms of beta-galactosidase, beta-glucosidase and N-acetyl-beta-glucosaminidase in normal and damaged kidneys were studied, using starch gel electrophoresis. The activities of both the lysosomal and the soluble forms of these enzymes decreased following the injection of the nephrotoxin, confirming the results obtained with whole homogenates. The relationship between the changes in renal enzyme activity and urinary enzyme excretion during the nephrotoxic process is discussed.", "contents": "Studies on the nephrotoxicity of p-nitrophenylarsonic acid: changes in rat kidney and urinary enzyme activities following the administration of p-nitrophenylarsonic acid. Histological studies showed that the administration of p-nitrophenylarsonic acid to rats resulted in renal tubular necrosis. The nephrotoxin was administered intraperitoneally and doses greater than 30 mg/kg were found to be fatal. The severity of the renal lesion depended on the amount of the nephrotoxin used. Elevated serum urea levels, urinary protein and volume were recorded over an 8-day period following the injection of the nephrotoxin. These changes were paralleled by an increase in the activity of lactate dehydrogenase, acid and alkaline phosphatase, N-acetyl-beta-glucosaminidase and beta-glucosidase in the urine. beta-Glycosidase activities increased in kidney homogenates, immediately after the injection of the nephrotoxin, but this eventually fell to well below the normal range. Subcellular fractions were prepared from sucrose homogenates by differential centrifugation and beta-glycosidases and cytochrome oxidase were used as enzyme markers. Only minor changes in the activity of cytochrome oxidase activity resulted from the administration of p-nitrophenylarsonic acid. One of the earliest indications of renal damage was a decrease in lysosomal latency. The activities of the lysosomal and soluble enzymes were elevated above normal during the first two days after the injection of p-nitrophenylarsonic acid, but they fell to values, significantly lower than normal, on the third day. The isoenzymic forms of beta-galactosidase, beta-glucosidase and N-acetyl-beta-glucosaminidase in normal and damaged kidneys were studied, using starch gel electrophoresis. The activities of both the lysosomal and the soluble forms of these enzymes decreased following the injection of the nephrotoxin, confirming the results obtained with whole homogenates. The relationship between the changes in renal enzyme activity and urinary enzyme excretion during the nephrotoxic process is discussed."}
{"id": "PMID:218745", "title": "Evaluation of smallpox vaccination policy.", "content": "During 1978 and 1979 the Global Commission for the Certification of Smallpox Eradication will proceed with verification of smallpox eradication in 31 countries. If current surveillance activities do not discover any further cases before the end of 1979, the world will be declared smallpox free. However, the recent occurrence of two laboratory associated smallpox cases in Birmingham, England, revealed that the stocks of variola virus held in at least 12 laboratories in the world pose a real danger to the achievement of smallpox eradication and efforts are being made to reduce the number of laboratories retaining the virus to not more than 4-all WHO collaborating centres-by 1980. Scientific data indicate the unlikelihood of smallpox recurring once it has been eradicated from the human population, although further confirmatory studies are continuing. If the Global Commission verifies the eradication of smallpox, continuation of smallpox vaccination will be unjustifiable in view of its severe complications, however infrequent, and the expected global savings that would result from the termination of vaccination programmes.", "contents": "Evaluation of smallpox vaccination policy. During 1978 and 1979 the Global Commission for the Certification of Smallpox Eradication will proceed with verification of smallpox eradication in 31 countries. If current surveillance activities do not discover any further cases before the end of 1979, the world will be declared smallpox free. However, the recent occurrence of two laboratory associated smallpox cases in Birmingham, England, revealed that the stocks of variola virus held in at least 12 laboratories in the world pose a real danger to the achievement of smallpox eradication and efforts are being made to reduce the number of laboratories retaining the virus to not more than 4-all WHO collaborating centres-by 1980. Scientific data indicate the unlikelihood of smallpox recurring once it has been eradicated from the human population, although further confirmatory studies are continuing. If the Global Commission verifies the eradication of smallpox, continuation of smallpox vaccination will be unjustifiable in view of its severe complications, however infrequent, and the expected global savings that would result from the termination of vaccination programmes."}
{"id": "PMID:218746", "title": "Epidemiological events surrounding a paralytic case of poliomyelitis in Sweden.", "content": "A case of clinical poliomyelitis occurred in Sweden in January 1977; it was the first indigenous case in Sweden since 1962. This incident was of particular interest as it provided an opportunity to study the spread of virus in a cluster of unvaccinated persons and in individuals more or less fully vaccinated with inactivated vaccine. The patient excreted wild type 2 virus and the same type was isolated from 25 other individuals, all of whom were close contacts of virus excretors. Among the close contacts, 14 of 20 unvaccinated preschool children were found to excrete virus, but excretion was not found in any of the 7 vaccinated children examined.", "contents": "Epidemiological events surrounding a paralytic case of poliomyelitis in Sweden. A case of clinical poliomyelitis occurred in Sweden in January 1977; it was the first indigenous case in Sweden since 1962. This incident was of particular interest as it provided an opportunity to study the spread of virus in a cluster of unvaccinated persons and in individuals more or less fully vaccinated with inactivated vaccine. The patient excreted wild type 2 virus and the same type was isolated from 25 other individuals, all of whom were close contacts of virus excretors. Among the close contacts, 14 of 20 unvaccinated preschool children were found to excrete virus, but excretion was not found in any of the 7 vaccinated children examined."}
{"id": "PMID:218748", "title": "Direct evidence for the presence of a different converting enzyme in the hamster cheek pouch.", "content": "Kininase II (angiotensin I-converting enzyme) is generally accepted to be the enzyme responsible for the conversion of angiotensin I (A I) to angiotensin II (A II). This study examined the response of the microvasculature of the hamster cheek pouch to the local application of A I, A II, and the renin substrate, tetradecapeptide (TDP). A I and TDP caused a localized vasoconstriction that was not blocked by converting enzyme inhibitors (CEI: BPF5a for A I and BPF5a and the nonapeptide inhibitor for TDP). However, both the A II antagonist [Sar1, Ala8]angiotensin II and the antiserum to A II blocked completely the A I- and TDP-induced vasoconstriction. Sixty-eight percent of the applied A I was converted to A II in the presence of CEI as well as in its absence. It is concluded that the vasculature of the hamster cheek pouch converts significant amounts of A I to A II by a route that does not involve kininase II.", "contents": "Direct evidence for the presence of a different converting enzyme in the hamster cheek pouch. Kininase II (angiotensin I-converting enzyme) is generally accepted to be the enzyme responsible for the conversion of angiotensin I (A I) to angiotensin II (A II). This study examined the response of the microvasculature of the hamster cheek pouch to the local application of A I, A II, and the renin substrate, tetradecapeptide (TDP). A I and TDP caused a localized vasoconstriction that was not blocked by converting enzyme inhibitors (CEI: BPF5a for A I and BPF5a and the nonapeptide inhibitor for TDP). However, both the A II antagonist [Sar1, Ala8]angiotensin II and the antiserum to A II blocked completely the A I- and TDP-induced vasoconstriction. Sixty-eight percent of the applied A I was converted to A II in the presence of CEI as well as in its absence. It is concluded that the vasculature of the hamster cheek pouch converts significant amounts of A I to A II by a route that does not involve kininase II."}
{"id": "PMID:218749", "title": "Reduction of plasma renin activity by inhibition of the fatty acid cyclooxygenase in human subjects: independence of sodium retention.", "content": "We carried out the present studies to determine whether the suppression of plasma renin activity (PRA) that follows inhibition of prostaglandin (PG) synthesis can be dissociated from the sodium-retaining effects of these drugs. In an initial investigation we studied the effect of indomethacin on PRA in normal subjects in balance on a 10 mM Na+ diet to prevent Na+ retention. Under these experimental conditions indomethacin did not lower PRA even though the fatty acid cyclooxygenase was inhibited, as indicated by a greater than 70% reduction in the major urinary metabolite of prostaglandin E (PGE-M). Sodium depletion leads to enhanced sympathetic activity. We therefore studied the effect of indomethacin on a group of subjects in 10 mM Na+ balance in whom the effect of increased beta-sympathetic activity was blocked by the administration of propranolol. In this group, indomethacin caused 65% suppression of PGE-M and had no effect on Na+ balance, but reversibly reduced PRA in the supine and upright positions by 84% and 70%, respectively. In normal subjects in 10 mM Na+ balance, the isoproterenol-induced increase in PRA also was unaffected by indomethacin. These data establish that inhibition of the cyclooxygenase can result in a reduction of PRA that is independent of changes in Na+ balance or beta-sympathetic tone.", "contents": "Reduction of plasma renin activity by inhibition of the fatty acid cyclooxygenase in human subjects: independence of sodium retention. We carried out the present studies to determine whether the suppression of plasma renin activity (PRA) that follows inhibition of prostaglandin (PG) synthesis can be dissociated from the sodium-retaining effects of these drugs. In an initial investigation we studied the effect of indomethacin on PRA in normal subjects in balance on a 10 mM Na+ diet to prevent Na+ retention. Under these experimental conditions indomethacin did not lower PRA even though the fatty acid cyclooxygenase was inhibited, as indicated by a greater than 70% reduction in the major urinary metabolite of prostaglandin E (PGE-M). Sodium depletion leads to enhanced sympathetic activity. We therefore studied the effect of indomethacin on a group of subjects in 10 mM Na+ balance in whom the effect of increased beta-sympathetic activity was blocked by the administration of propranolol. In this group, indomethacin caused 65% suppression of PGE-M and had no effect on Na+ balance, but reversibly reduced PRA in the supine and upright positions by 84% and 70%, respectively. In normal subjects in 10 mM Na+ balance, the isoproterenol-induced increase in PRA also was unaffected by indomethacin. These data establish that inhibition of the cyclooxygenase can result in a reduction of PRA that is independent of changes in Na+ balance or beta-sympathetic tone."}
{"id": "PMID:218750", "title": "Suppression of plasma ACTH concentration by angiotensin II infusion in normal humans and in a subject with a steroid 17 alpha-hydroxylase defect.", "content": "Six healthy subjects were infused with angiotensin II and plasma concentrations of angiotensin, ACTH and cortisol were measured before, during and after the infusion. In all cases the plasma ACTH concentration fell as plasma angiotensin increased and rose again, sometimes to higher than basal levels, when the angiotensin infusion was terminated. These effects were most marked at the highest rate of infusion (8 pmol/kg/min) and, at the lower rates (2 and 4 pmol/kg/min), there was some recovery of ACTH levels during the infusion period in some subjects. Plasma ACTH concentrations also fell when angiotensin was infused into a patient with high ACTH levels due to a steroid 17 alpha-hydroxylation defect. The inhibition of ACTH secretion is not due to a rise in plasma cortisol operating a negative feedback inhibition. It could be a direct effect of the infused angiotensin on the brain-hypothalamus-pituitary complex or an effect on the metabolism of ACTH.", "contents": "Suppression of plasma ACTH concentration by angiotensin II infusion in normal humans and in a subject with a steroid 17 alpha-hydroxylase defect. Six healthy subjects were infused with angiotensin II and plasma concentrations of angiotensin, ACTH and cortisol were measured before, during and after the infusion. In all cases the plasma ACTH concentration fell as plasma angiotensin increased and rose again, sometimes to higher than basal levels, when the angiotensin infusion was terminated. These effects were most marked at the highest rate of infusion (8 pmol/kg/min) and, at the lower rates (2 and 4 pmol/kg/min), there was some recovery of ACTH levels during the infusion period in some subjects. Plasma ACTH concentrations also fell when angiotensin was infused into a patient with high ACTH levels due to a steroid 17 alpha-hydroxylation defect. The inhibition of ACTH secretion is not due to a rise in plasma cortisol operating a negative feedback inhibition. It could be a direct effect of the infused angiotensin on the brain-hypothalamus-pituitary complex or an effect on the metabolism of ACTH."}
{"id": "PMID:218752", "title": "Lipodystrophy with hyperlipidaemia: the role of insulin in very low density lipoprotein over-synthesis.", "content": "A patient with partial lipodystrophy is described in whom hypertriglyceridaemia was accompanied by marked hyperinsulinaemia. The hyperlipidaemia was due to increased plasma levels of very low density lipoprotein (VLDL). Kinetic studies, performed after injection of autologous radioiodinated VLDL, indicated that the raised VLDL levels were associated with over-production of this lipoprotein. Administration of diazoxide led to a substantial fall in serum insulin levels, accompanied by reduction in VLDL production and in serum triglyceride concentration. The possible role of insulin in inducing hyperlipidaemia by causing over-production of VLDL is discussed.", "contents": "Lipodystrophy with hyperlipidaemia: the role of insulin in very low density lipoprotein over-synthesis. A patient with partial lipodystrophy is described in whom hypertriglyceridaemia was accompanied by marked hyperinsulinaemia. The hyperlipidaemia was due to increased plasma levels of very low density lipoprotein (VLDL). Kinetic studies, performed after injection of autologous radioiodinated VLDL, indicated that the raised VLDL levels were associated with over-production of this lipoprotein. Administration of diazoxide led to a substantial fall in serum insulin levels, accompanied by reduction in VLDL production and in serum triglyceride concentration. The possible role of insulin in inducing hyperlipidaemia by causing over-production of VLDL is discussed."}
{"id": "PMID:218753", "title": "Testicular function following irradiation of the human prepubertal testis.", "content": "Testicular function was studied in ten men, aged between 17 and 36 years, who had received irradiation for a nephroblastoma during childhood. The dose of scattered irradiation to the testes ranged from 268 to 983 rad. Eight subjects had either oligo- or azoospermia (0 to 5.6 million/ml), seven of whom had an elevated serum follicle-stimulating hormone (FSH) level. One subject showed evidence of Leydig cell dysfunction with a raised serum luteinizing hormone level (LH) and a low plasma testosterone concentration. A second group of eight prepubertal males, aged between 8 and 14 years, were studied. These had also been irradiated for abdominal malignancies during childhood and received a similar dose of irradiation to the testis as the first group studied. The plasma testosterone levels were within the normal range for prepubertal boys in all eight. The mean gonadotrophin levels were not significantly different from the mean levels of normal prepubertal males. Thus irradiation-induced damage to the germinal epithelium in prepubertal boys produces raised FSH levels after puberty but not before it. We conclude, therefore, that inhibition has a minor role in the control of the prepubertal hypothalamic-pituitary testicular axis and its contribution to gonadal control of gonadotrophin secretion changes with sexual maturation.", "contents": "Testicular function following irradiation of the human prepubertal testis. Testicular function was studied in ten men, aged between 17 and 36 years, who had received irradiation for a nephroblastoma during childhood. The dose of scattered irradiation to the testes ranged from 268 to 983 rad. Eight subjects had either oligo- or azoospermia (0 to 5.6 million/ml), seven of whom had an elevated serum follicle-stimulating hormone (FSH) level. One subject showed evidence of Leydig cell dysfunction with a raised serum luteinizing hormone level (LH) and a low plasma testosterone concentration. A second group of eight prepubertal males, aged between 8 and 14 years, were studied. These had also been irradiated for abdominal malignancies during childhood and received a similar dose of irradiation to the testis as the first group studied. The plasma testosterone levels were within the normal range for prepubertal boys in all eight. The mean gonadotrophin levels were not significantly different from the mean levels of normal prepubertal males. Thus irradiation-induced damage to the germinal epithelium in prepubertal boys produces raised FSH levels after puberty but not before it. We conclude, therefore, that inhibition has a minor role in the control of the prepubertal hypothalamic-pituitary testicular axis and its contribution to gonadal control of gonadotrophin secretion changes with sexual maturation."}
{"id": "PMID:218754", "title": "Plasma ACTH and cortisol profiles in Addisonian patients receiving conventional substitution therapy.", "content": "Plasma ACTH and cortisol profiles were studied over 24 h in five Addisonian patients maintained in good health by conventional gluco- and mineralocorticoid treatment. Patients received their usual treatment (15--30 mg cortisol daily) in divided doses at 08.00 and 16.00 hours. Plasma cortisol concentrations differed from those of control subjects in being higher from 08.00 hours-noon and 17.00-18.00 hours and were unmeasurable (less than 20 nmol/l) during the period of active cortisol secretion (03.00-08.00 hours) observed in normal subjects. Peak plasma ACTH levels (618- greater than 1600 ng/l) occurred at 08.00-09.00 hours in the Addisonian patients and were much greater than those seen in control subjects (60-220 ng/l). Despite this, plasma ACTH fell promptly within 3 h of the morning dose to less than 100 ng/l and levels were indistinguishable from those seen in normal subjects over the period 12.00-02.00 hours. These results show that there are substantial differences between treated Addisonian and control subjects in respect of plasma cortisol and ACTH concentrations. The findings may lead to a better understanding of ACTH-cortisol relationships in disease states, including congenital adrenal hyperplasia where control of excessive ACTH secretion is clinically desirable.", "contents": "Plasma ACTH and cortisol profiles in Addisonian patients receiving conventional substitution therapy. Plasma ACTH and cortisol profiles were studied over 24 h in five Addisonian patients maintained in good health by conventional gluco- and mineralocorticoid treatment. Patients received their usual treatment (15--30 mg cortisol daily) in divided doses at 08.00 and 16.00 hours. Plasma cortisol concentrations differed from those of control subjects in being higher from 08.00 hours-noon and 17.00-18.00 hours and were unmeasurable (less than 20 nmol/l) during the period of active cortisol secretion (03.00-08.00 hours) observed in normal subjects. Peak plasma ACTH levels (618- greater than 1600 ng/l) occurred at 08.00-09.00 hours in the Addisonian patients and were much greater than those seen in control subjects (60-220 ng/l). Despite this, plasma ACTH fell promptly within 3 h of the morning dose to less than 100 ng/l and levels were indistinguishable from those seen in normal subjects over the period 12.00-02.00 hours. These results show that there are substantial differences between treated Addisonian and control subjects in respect of plasma cortisol and ACTH concentrations. The findings may lead to a better understanding of ACTH-cortisol relationships in disease states, including congenital adrenal hyperplasia where control of excessive ACTH secretion is clinically desirable."}
{"id": "PMID:218759", "title": "Cytomegalovirus infection and chronic hemodialysis.", "content": "Serologic and virologic studies of cytomegalovirus (CMV), a virus infection often disseminated in immunosuppressed patients, were initiated among hemodialysis patients, home dialysis partners, hemodialysis center personnel, and several groups of patients. No evidence was found of activation or persistence of CMV infections in connection with chronic renal disease or in association with hemodialysis. Evidence of increased CMV activation and/or infection was found among individuals who had re-entered the dialysis program following renal allograft rejection. The data indicate that dialysis personnel and home dialysis partners are not at increased risk for CMV infection. The findings of this study, which contrast with those pertaining to hepatitis B infection, suggest that different mechanisms are responsible for establishing both infection and persistence of CMV and hepatitis B.", "contents": "Cytomegalovirus infection and chronic hemodialysis. Serologic and virologic studies of cytomegalovirus (CMV), a virus infection often disseminated in immunosuppressed patients, were initiated among hemodialysis patients, home dialysis partners, hemodialysis center personnel, and several groups of patients. No evidence was found of activation or persistence of CMV infections in connection with chronic renal disease or in association with hemodialysis. Evidence of increased CMV activation and/or infection was found among individuals who had re-entered the dialysis program following renal allograft rejection. The data indicate that dialysis personnel and home dialysis partners are not at increased risk for CMV infection. The findings of this study, which contrast with those pertaining to hepatitis B infection, suggest that different mechanisms are responsible for establishing both infection and persistence of CMV and hepatitis B."}
{"id": "PMID:218761", "title": "Biparietal osteodystrophy.", "content": "Following an exhaustive literature review of 126 cases, a personal series of 8 instances is presented. The following inferences are drawn: 1) the condition is not an anatomical variant, but a pathological lesion. 2) the lesion occurs in all races, and at all latitudes; its prevalence can be estimated to range between 0.4 and 0.5%. 3) the lesion occurs predominantly in females (sex ratio male: female = 1 : 2.5) and after the age of 60. 4) histological evidence indicated erosion of the external table, compensated by remodeling of the diploe, with resultant loss of the diploe. 5) Neither senility nor senescence, nor chronic trauma, nor muscular traction, nor inflammation, can explain the lesion, its symmetry, its site or its age/sex predilection.", "contents": "Biparietal osteodystrophy. Following an exhaustive literature review of 126 cases, a personal series of 8 instances is presented. The following inferences are drawn: 1) the condition is not an anatomical variant, but a pathological lesion. 2) the lesion occurs in all races, and at all latitudes; its prevalence can be estimated to range between 0.4 and 0.5%. 3) the lesion occurs predominantly in females (sex ratio male: female = 1 : 2.5) and after the age of 60. 4) histological evidence indicated erosion of the external table, compensated by remodeling of the diploe, with resultant loss of the diploe. 5) Neither senility nor senescence, nor chronic trauma, nor muscular traction, nor inflammation, can explain the lesion, its symmetry, its site or its age/sex predilection."}
{"id": "PMID:218763", "title": "Computed tomography of supratentorial astrocytoma.", "content": "In a group of 40 astrocytomas the C.T. appearance was correlated with the grade of malignancy. On the plain scan the majority presented an irregular, nonhomogeneous low density lesion, better demarcatable in high than in low grade astrocytomas. Contrast enhancement was seen in 28 of the 32 high grade astrocytomas, 50% of the annular, 25% of the nodular and 25% of the mixed type. Six of the 8 low grade astrocytomas showed no contrast enhancement and 1 showed an annular type lesion. A relationship was found between the degree of contrast enhancement and the vascularity. Mass effect was observed in all but 1 patient, but more pronounced in high grade astrocytomas. At the first interpretation 98% were recognized as a lesion, 93% as a tumor and 68% as an astrocytoma. One false negative and no false postive C.T.scans were obtained. In review, high and low grade malignancies were correctly differentiated in 90%. As a screening method, the combination of EEG and echo equalled C.T.; in establishing a definite diagnosis angiography was inferior to C.T. Solely on the basis of the C.T. appearance, astrocytomas can hardly be differentiated from the other malignant brain tumors, but the grade of malignancy can be predicted reliably.", "contents": "Computed tomography of supratentorial astrocytoma. In a group of 40 astrocytomas the C.T. appearance was correlated with the grade of malignancy. On the plain scan the majority presented an irregular, nonhomogeneous low density lesion, better demarcatable in high than in low grade astrocytomas. Contrast enhancement was seen in 28 of the 32 high grade astrocytomas, 50% of the annular, 25% of the nodular and 25% of the mixed type. Six of the 8 low grade astrocytomas showed no contrast enhancement and 1 showed an annular type lesion. A relationship was found between the degree of contrast enhancement and the vascularity. Mass effect was observed in all but 1 patient, but more pronounced in high grade astrocytomas. At the first interpretation 98% were recognized as a lesion, 93% as a tumor and 68% as an astrocytoma. One false negative and no false postive C.T.scans were obtained. In review, high and low grade malignancies were correctly differentiated in 90%. As a screening method, the combination of EEG and echo equalled C.T.; in establishing a definite diagnosis angiography was inferior to C.T. Solely on the basis of the C.T. appearance, astrocytomas can hardly be differentiated from the other malignant brain tumors, but the grade of malignancy can be predicted reliably."}
{"id": "PMID:218764", "title": "A study of the anatomy of the anterior communicating artery with the aid of the operating microscope.", "content": "The anatomy of the Anterior Communicating Artery complex is studied with the aid of the Zeiss operating microscope in 75 human brains removed at autopsy. The variations in the structure of the Anterior Communicating Artery and the A1 and A2 segments of the Anterior Cerebral Artery are reported. Special attention is given to the site of origin and number of branches from the Anterior Communicating Artery and the site of origin of Heubner's arteries. The necessity of using the operating microscope during surgical treatment of aneurysms of the Anterior Communicating Artery complex is stressed.", "contents": "A study of the anatomy of the anterior communicating artery with the aid of the operating microscope. The anatomy of the Anterior Communicating Artery complex is studied with the aid of the Zeiss operating microscope in 75 human brains removed at autopsy. The variations in the structure of the Anterior Communicating Artery and the A1 and A2 segments of the Anterior Cerebral Artery are reported. Special attention is given to the site of origin and number of branches from the Anterior Communicating Artery and the site of origin of Heubner's arteries. The necessity of using the operating microscope during surgical treatment of aneurysms of the Anterior Communicating Artery complex is stressed."}
{"id": "PMID:218765", "title": "A tumour in the cerebellopontine angle region: an unusual case.", "content": "This paper describes a nearly 60-year old patient with unilateral hearing loss, developed in one year, and complaints of tinnitus and dizziness. Additional findings were unilateral peripheral facial paresis and a diminished corneal reflex. The cause was found to be a metastasis of an anaplastic carcinoma, localized at the site of the internal acoustic porus.", "contents": "A tumour in the cerebellopontine angle region: an unusual case. This paper describes a nearly 60-year old patient with unilateral hearing loss, developed in one year, and complaints of tinnitus and dizziness. Additional findings were unilateral peripheral facial paresis and a diminished corneal reflex. The cause was found to be a metastasis of an anaplastic carcinoma, localized at the site of the internal acoustic porus."}
{"id": "PMID:218766", "title": "Cerebral metastasis without known primary tumour: a retrospective study.", "content": "A retrospective study was made of 19 patients who underwent operation for an intracerebral metastasis of an unknown primary tumour. Most patients survived for a few months only, with 2 remarkable ecceptions. In only 8 of them, the primary tumour became manifest in the further course of the illness.", "contents": "Cerebral metastasis without known primary tumour: a retrospective study. A retrospective study was made of 19 patients who underwent operation for an intracerebral metastasis of an unknown primary tumour. Most patients survived for a few months only, with 2 remarkable ecceptions. In only 8 of them, the primary tumour became manifest in the further course of the illness."}
{"id": "PMID:218768", "title": "Atlas of 99mTc-methylene diphosphonate renal images in pediatric oncology.", "content": "We describe the urinary tract abnormalities observed with bone scintigraphy during the evaluation of malignant disease. The possible abnormal renal patterns are discussed.", "contents": "Atlas of 99mTc-methylene diphosphonate renal images in pediatric oncology. We describe the urinary tract abnormalities observed with bone scintigraphy during the evaluation of malignant disease. The possible abnormal renal patterns are discussed."}
{"id": "PMID:218770", "title": "Myocardial infarct imaging with 99mTc-pyrophosphate and 99mTc-methylene diphosphonate: lack of correlation.", "content": "A prospective study of eight patients with recent transmural myocardial infarction was performed using 99mTc-Sn-pyrophosphate and 99mTc-Sn-methylene diphosphonate in each patient. All pyrophosphate scans were strongly positive whereas the diphosphonate scan was strongly positive in only one case. We conclude that 99mTc-Sn-pyrophosphate is preferable to 99mTc-Sn-methylene diphosphonate for myocardial imaging.", "contents": "Myocardial infarct imaging with 99mTc-pyrophosphate and 99mTc-methylene diphosphonate: lack of correlation. A prospective study of eight patients with recent transmural myocardial infarction was performed using 99mTc-Sn-pyrophosphate and 99mTc-Sn-methylene diphosphonate in each patient. All pyrophosphate scans were strongly positive whereas the diphosphonate scan was strongly positive in only one case. We conclude that 99mTc-Sn-pyrophosphate is preferable to 99mTc-Sn-methylene diphosphonate for myocardial imaging."}
{"id": "PMID:218772", "title": "Circadian rhythms of the functions of thrombocytes and basophils in the blood of healthy volunteers and of patients with ischaemic heart disease.", "content": "The circadian rhythms of the functions of the cellular components of haemostasis, and their response to administration of ACTH, were studied in 30 healthy volunteers and in 17 patients with cardiosclerosis secondary to past myocardial infarction. A biphasic periodicity was found of the counts and functional activities of thrombocytes and basophilic leukocytes during 24-h periods. The phase of peak activities of both formed blood elements was established between 11.00 and 14.00 hours; in the night their functional capacities were lower than in the morning. Administration of ACTH elicited analogous shifts in the above mentioned indicators, but with a faster development of the first phase. In ischaemic heart disease the normal circadian rhythm of functions of the specified indicators was disturbed, and they exhibited signs of inertia, which phenomenon, in the author's opinion, reflects a lowered reliability of function of the haemostatic system.", "contents": "Circadian rhythms of the functions of thrombocytes and basophils in the blood of healthy volunteers and of patients with ischaemic heart disease. The circadian rhythms of the functions of the cellular components of haemostasis, and their response to administration of ACTH, were studied in 30 healthy volunteers and in 17 patients with cardiosclerosis secondary to past myocardial infarction. A biphasic periodicity was found of the counts and functional activities of thrombocytes and basophilic leukocytes during 24-h periods. The phase of peak activities of both formed blood elements was established between 11.00 and 14.00 hours; in the night their functional capacities were lower than in the morning. Administration of ACTH elicited analogous shifts in the above mentioned indicators, but with a faster development of the first phase. In ischaemic heart disease the normal circadian rhythm of functions of the specified indicators was disturbed, and they exhibited signs of inertia, which phenomenon, in the author's opinion, reflects a lowered reliability of function of the haemostatic system."}
{"id": "PMID:218777", "title": "[Macro-electrode recording in man's brain-stem 1. Electrical activity during wakefulness and nightsleep (author's transl)].", "content": "In the context of a functional treatment for pain five patients had electrodes chronically implanted in the periaqueductal gray matter (PGM) and at the same time in thalamic nuclei. The spontaneous activity of these structures was analyzed in comparison with the simultaneously recorded scalp-EEG. The structure-specific differences between the activity of the PGM and the thalamic nuclei were pointed out. In waking state a close functional relation between the alpha-activity of the PGM and the scalp-EEG was found. Physiological sleep patterns were recorded in the mesencephalon earleir than at the surface. REM-phases were initiated by 4/sec rhythms in the PGM. During rapid eye movements sharp waves in the PGM appeared which are evidently related to the eye movements themselves. The findings are discussed in reference to the literature. Special emphasis is placed on the anatomical connexions between the explored mesencephalic and thalamic structures and the temporo-occipital cortex and on the role of ponto-mesencephalic structures in slow-wave-sleep and REM-sleep.", "contents": "[Macro-electrode recording in man's brain-stem 1. Electrical activity during wakefulness and nightsleep (author's transl)]. In the context of a functional treatment for pain five patients had electrodes chronically implanted in the periaqueductal gray matter (PGM) and at the same time in thalamic nuclei. The spontaneous activity of these structures was analyzed in comparison with the simultaneously recorded scalp-EEG. The structure-specific differences between the activity of the PGM and the thalamic nuclei were pointed out. In waking state a close functional relation between the alpha-activity of the PGM and the scalp-EEG was found. Physiological sleep patterns were recorded in the mesencephalon earleir than at the surface. REM-phases were initiated by 4/sec rhythms in the PGM. During rapid eye movements sharp waves in the PGM appeared which are evidently related to the eye movements themselves. The findings are discussed in reference to the literature. Special emphasis is placed on the anatomical connexions between the explored mesencephalic and thalamic structures and the temporo-occipital cortex and on the role of ponto-mesencephalic structures in slow-wave-sleep and REM-sleep."}
{"id": "PMID:218778", "title": "Increase of ceruloplasmin level in blood of rats after ACTH.", "content": "The level of ceruloplasmin in plasma was measured as polyphenol oxidase activity in following groups of rats: 1. controls; 2. adrenalectomized; 3. shamadrenalectomized; 4. formalin arthritis; 5. ACTH treated (25 micrograms ACTH daily for 5 days); 6. adrenalectomized and ACTH treated (as in a previous group). The level of ceruloplasmin was markedly increased after formalin arthritis, after ACTH treatment in controls and in adrenalectomized animals.", "contents": "Increase of ceruloplasmin level in blood of rats after ACTH. The level of ceruloplasmin in plasma was measured as polyphenol oxidase activity in following groups of rats: 1. controls; 2. adrenalectomized; 3. shamadrenalectomized; 4. formalin arthritis; 5. ACTH treated (25 micrograms ACTH daily for 5 days); 6. adrenalectomized and ACTH treated (as in a previous group). The level of ceruloplasmin was markedly increased after formalin arthritis, after ACTH treatment in controls and in adrenalectomized animals."}
{"id": "PMID:218779", "title": "Evidence for the involvement of guanosine 3',5'-cyclic monophosphate in the regulation of gonadotropin release.", "content": "Addition of dibutyryl adenosine 3'-5'-cyclic monophosphate (DBcAMP) or dibutyryl guanosine 3',5'-cyclic monophosphate (DBcGMP; 1--6mM) to to enzymatically dispersed, overnight-cultured rat anterior pituitary cell preparations stimulated the release of gonadotropins (LH and FSH) from the cells into the incubation medium. Stimulation of gonadotropin release by DBcGMP was observed after only 10 min of incubation, whereas that caused by DBcAMP appeared at 180 min. Synthetic LHRH (2.5 X 10(-9) M) induced a small, transient increase in intracellular cAMP content (+16%, P less than 0.05, after 5 min coincubation), while levels of cGMP in the same cells were rapidly and markedly low for 2 h. The decrease in cGMP content was accompanied by a discharge of gonadotropins lasting for 2 h, which was detectable after 5 min in the case of LH and after 10 min in the case of FSH. These results strongly suggest that cGMP might be an intracellular mediator in the process of LHRH-stimulated release of gonadotropins.", "contents": "Evidence for the involvement of guanosine 3',5'-cyclic monophosphate in the regulation of gonadotropin release. Addition of dibutyryl adenosine 3'-5'-cyclic monophosphate (DBcAMP) or dibutyryl guanosine 3',5'-cyclic monophosphate (DBcGMP; 1--6mM) to to enzymatically dispersed, overnight-cultured rat anterior pituitary cell preparations stimulated the release of gonadotropins (LH and FSH) from the cells into the incubation medium. Stimulation of gonadotropin release by DBcGMP was observed after only 10 min of incubation, whereas that caused by DBcAMP appeared at 180 min. Synthetic LHRH (2.5 X 10(-9) M) induced a small, transient increase in intracellular cAMP content (+16%, P less than 0.05, after 5 min coincubation), while levels of cGMP in the same cells were rapidly and markedly low for 2 h. The decrease in cGMP content was accompanied by a discharge of gonadotropins lasting for 2 h, which was detectable after 5 min in the case of LH and after 10 min in the case of FSH. These results strongly suggest that cGMP might be an intracellular mediator in the process of LHRH-stimulated release of gonadotropins."}
{"id": "PMID:218780", "title": "Phosphodiesterase and its Ca2+-dependent activating factor in bovine thyroid.", "content": "Properties of cyclic 3',5'-nucleotide phosphodiesterase in the 100,500 X g supernatant of the bovine thyroid were investigated. The enzyme activity was measured by a radioisotopic method using an anionic-exchange resin, and it was found that the activity was stimulated by Mg2+. Sephadex G-200 gel filtration separated the supernatant into an activating factor, which required the presence of Ca2+, and an enzyme form dependent on the factor. The molecular weights were estimated to be 25,000 and 130,000, respectively. There appeared to be another enzyme form of cAMP phosphodiesterase with different dependence on the activating factor as suggested by gel filtration, but this enzyme form could not be clearly separated. cGMP phosphodiesterase purified by gel filtration showed biphasic kinetic behavior in the absence of Ca2+ and the activating factor, whereas, in their presence, the Lineweaver-Burk plot gave a single Km. The activating mechanism of phosphodiesterase may play a role in the control of concentrations of intracellular cyclic 3',5'-nucleotides in the bovine thyroid.", "contents": "Phosphodiesterase and its Ca2+-dependent activating factor in bovine thyroid. Properties of cyclic 3',5'-nucleotide phosphodiesterase in the 100,500 X g supernatant of the bovine thyroid were investigated. The enzyme activity was measured by a radioisotopic method using an anionic-exchange resin, and it was found that the activity was stimulated by Mg2+. Sephadex G-200 gel filtration separated the supernatant into an activating factor, which required the presence of Ca2+, and an enzyme form dependent on the factor. The molecular weights were estimated to be 25,000 and 130,000, respectively. There appeared to be another enzyme form of cAMP phosphodiesterase with different dependence on the activating factor as suggested by gel filtration, but this enzyme form could not be clearly separated. cGMP phosphodiesterase purified by gel filtration showed biphasic kinetic behavior in the absence of Ca2+ and the activating factor, whereas, in their presence, the Lineweaver-Burk plot gave a single Km. The activating mechanism of phosphodiesterase may play a role in the control of concentrations of intracellular cyclic 3',5'-nucleotides in the bovine thyroid."}
{"id": "PMID:218781", "title": "Biochemical studies on rats with insulin-secreting islet cell tumors induced by streptozotocin: with special reference to physiological response to oral glucose load in the course of and after tumor induction.", "content": "Pancreatic islet cell tumors were induced in 32 of 49 male Wistar rats (73%) surviving 9 months or longer following treatment with streptozotocin alone, with streptozotocin and nicotinamide, or with streptozotocin and picolinamide. Serial oral glucose tolerance tests in rats treated with streptozotocin and nicotinamide showed that the elevation of blood glucose levels after oral glucose load was depressed significantly 7 months after treatment. Plasma insulin responses were distinctly elevated 9 months after treatment. Blood glucose levels remained lower and plasma insulin levels rose markedly after a glucose load in tumor-bearing rats as compared to the response of tumor-free rats. These findings suggest that pancreatic islet cell tumors induced by streptozotocin with and without combined treatment are insulin-secreting, and that streptozotocin itself has oncogenic effects on the rat pancreas. Mean insulin concentration in islet cell tumors amounted to 401 U/g wet wt, whereas the concentration was 14 U/g wet wt in the pancreatic tissue from tumor-free rats.", "contents": "Biochemical studies on rats with insulin-secreting islet cell tumors induced by streptozotocin: with special reference to physiological response to oral glucose load in the course of and after tumor induction. Pancreatic islet cell tumors were induced in 32 of 49 male Wistar rats (73%) surviving 9 months or longer following treatment with streptozotocin alone, with streptozotocin and nicotinamide, or with streptozotocin and picolinamide. Serial oral glucose tolerance tests in rats treated with streptozotocin and nicotinamide showed that the elevation of blood glucose levels after oral glucose load was depressed significantly 7 months after treatment. Plasma insulin responses were distinctly elevated 9 months after treatment. Blood glucose levels remained lower and plasma insulin levels rose markedly after a glucose load in tumor-bearing rats as compared to the response of tumor-free rats. These findings suggest that pancreatic islet cell tumors induced by streptozotocin with and without combined treatment are insulin-secreting, and that streptozotocin itself has oncogenic effects on the rat pancreas. Mean insulin concentration in islet cell tumors amounted to 401 U/g wet wt, whereas the concentration was 14 U/g wet wt in the pancreatic tissue from tumor-free rats."}
{"id": "PMID:218783", "title": "Growth hormone causes rapid induction of lactogenic receptor activity in the Snell dwarf mouse liver.", "content": "The Snell dwarf mouse (dw/dw) has no detectable PRL-binding sites in the microsomal fractions of its liver. Both bGH and bPRL, purified by preparative gel electrophoresis, induce PRL-binding sites when injected into dw/dw. Intraperitoneal injection of 100 micrograms bGH every 8 h results in the appearance of a high affinity PRL receptor 8--16 h after initiation of treatment. This induced binding capacity plateaus after 32 h of treatment and subsequently decreases to nondetectable levels 48 h after the last injection. [125I]Iodo-ovine PRL is displaced from the induced receptor equally well by similar concentrations of ovine PRL, human GH, and bovine PRL, but is displaced by bovine GH (bGH) only at approximately 100-fold higher concentrations. While untreated dw/dw livers do possess high affinity bGH-binding sites, treatment with bGH did not alter the bGH-binding activity. Treatment of dw/dw with cycloheximide does not prevent induction of PRL receptors by bGH injections. These observations indicate that bGH induces the PRL receptor by interacting with the cell at some point distal to the induced receptor site and does not require the synthesis of new proteins.", "contents": "Growth hormone causes rapid induction of lactogenic receptor activity in the Snell dwarf mouse liver. The Snell dwarf mouse (dw/dw) has no detectable PRL-binding sites in the microsomal fractions of its liver. Both bGH and bPRL, purified by preparative gel electrophoresis, induce PRL-binding sites when injected into dw/dw. Intraperitoneal injection of 100 micrograms bGH every 8 h results in the appearance of a high affinity PRL receptor 8--16 h after initiation of treatment. This induced binding capacity plateaus after 32 h of treatment and subsequently decreases to nondetectable levels 48 h after the last injection. [125I]Iodo-ovine PRL is displaced from the induced receptor equally well by similar concentrations of ovine PRL, human GH, and bovine PRL, but is displaced by bovine GH (bGH) only at approximately 100-fold higher concentrations. While untreated dw/dw livers do possess high affinity bGH-binding sites, treatment with bGH did not alter the bGH-binding activity. Treatment of dw/dw with cycloheximide does not prevent induction of PRL receptors by bGH injections. These observations indicate that bGH induces the PRL receptor by interacting with the cell at some point distal to the induced receptor site and does not require the synthesis of new proteins."}
{"id": "PMID:218784", "title": "Kinetics of dog thyroid secretion in vitro.", "content": "The time sequence of radioiodine sequestration and secretion (BE131I) have been compared in dog thyroid slices prelabeled with 131I in vivo and incubated in vitro with or without TSH. Sequestration has been taken to be the amount of radioiodine present in phagocytic vacuoles or colloid droplets; the TSH or (Bu)2cAMP stimulation of the basal values was suppressed by endocytosis blocking drugs. TSH induced a sequestrated radioactivity (S) after 5 min and a stimulated secretion after 20 min. The secretion rate was constant: 1%/h (mean +/- SD = 1.0 +/- 0.4; n = 7) of the total radioactivity of the slices. At equilibrium, S was constant and equal to less than 1% of the total radioactivity. The half-life of S, assuming a disappearance rate proportional to S, was 26 min (26 +/- 4; n = 5); assuming a disappearance rate independent of S, the lifetime was 44 min (44 +/- 7; n = 6). At the steady state, the limiting step of maximally stimulated secretion was the hydrolysis of the sequestrated radioactivity and endocytosis rate was equal to secretion rate. Without TSH, a constant BEI release (0.23% +/- 0.07%/h; n = 7), insensitive to cytochalasin B, was observed, which corresponded to basal secretion.", "contents": "Kinetics of dog thyroid secretion in vitro. The time sequence of radioiodine sequestration and secretion (BE131I) have been compared in dog thyroid slices prelabeled with 131I in vivo and incubated in vitro with or without TSH. Sequestration has been taken to be the amount of radioiodine present in phagocytic vacuoles or colloid droplets; the TSH or (Bu)2cAMP stimulation of the basal values was suppressed by endocytosis blocking drugs. TSH induced a sequestrated radioactivity (S) after 5 min and a stimulated secretion after 20 min. The secretion rate was constant: 1%/h (mean +/- SD = 1.0 +/- 0.4; n = 7) of the total radioactivity of the slices. At equilibrium, S was constant and equal to less than 1% of the total radioactivity. The half-life of S, assuming a disappearance rate proportional to S, was 26 min (26 +/- 4; n = 5); assuming a disappearance rate independent of S, the lifetime was 44 min (44 +/- 7; n = 6). At the steady state, the limiting step of maximally stimulated secretion was the hydrolysis of the sequestrated radioactivity and endocytosis rate was equal to secretion rate. Without TSH, a constant BEI release (0.23% +/- 0.07%/h; n = 7), insensitive to cytochalasin B, was observed, which corresponded to basal secretion."}
{"id": "PMID:218785", "title": "Estradiol inhibition of luteinizing hormone-stimulated progesterone synthesis in isolated bovine luteal cells.", "content": "The effects of several steroid hormones on progesterone synthesis and cAMP accumulation in isolated bovine corpora luteal cells were investigated in an attempt to determine if any of the steroids would affect the basal level of these processes or their response to gonadotropin. Isolated bovine corpora luteal cells responded to LH with a significant (P less than 0.05) increase in progesterone synthesis and cAMP accumulation when incubated at 37 C for up to 1 h. Exogenous cAMP and analogs of cAMP also significantly stimulated steroidogenesis in these incubated cells. Stimulation of progesterone synthesis by 1 microgram/ml LH was significantly suppressed (P less than 0.05) in the presence of 5--10 microgram/ml estradiol. This inhibition appeared to be largely specific for 17beta-estradiol, in that other steroids such as estrone, estriol, 17alpha-estradiol, cortisol, and dihydrotestosterone were not inhibitory. Testosterone was found to be inhibitory, but it is uncertain if this effect was due to the androgen itself or to its conversion to estradiol. Estradiol did not affect the increase in endogenous cAMP caused by LH in these cells, but did inhibit the effect of exogenous dibutyryl cAMP on progesterone synthesis. The magnitude of this inhibition of the effect of dibutyryl cAMP was not, however, equal to the estradiol inhibition of the stimulation of progesterone synthesis by LH. These data indicate that estradiol, a possible physiological luteolytic agent, has a direct inhibitory action on the corpus luteum and produces its suppression by blocking the stimulatory effect of LH at a step after cAMP.", "contents": "Estradiol inhibition of luteinizing hormone-stimulated progesterone synthesis in isolated bovine luteal cells. The effects of several steroid hormones on progesterone synthesis and cAMP accumulation in isolated bovine corpora luteal cells were investigated in an attempt to determine if any of the steroids would affect the basal level of these processes or their response to gonadotropin. Isolated bovine corpora luteal cells responded to LH with a significant (P less than 0.05) increase in progesterone synthesis and cAMP accumulation when incubated at 37 C for up to 1 h. Exogenous cAMP and analogs of cAMP also significantly stimulated steroidogenesis in these incubated cells. Stimulation of progesterone synthesis by 1 microgram/ml LH was significantly suppressed (P less than 0.05) in the presence of 5--10 microgram/ml estradiol. This inhibition appeared to be largely specific for 17beta-estradiol, in that other steroids such as estrone, estriol, 17alpha-estradiol, cortisol, and dihydrotestosterone were not inhibitory. Testosterone was found to be inhibitory, but it is uncertain if this effect was due to the androgen itself or to its conversion to estradiol. Estradiol did not affect the increase in endogenous cAMP caused by LH in these cells, but did inhibit the effect of exogenous dibutyryl cAMP on progesterone synthesis. The magnitude of this inhibition of the effect of dibutyryl cAMP was not, however, equal to the estradiol inhibition of the stimulation of progesterone synthesis by LH. These data indicate that estradiol, a possible physiological luteolytic agent, has a direct inhibitory action on the corpus luteum and produces its suppression by blocking the stimulatory effect of LH at a step after cAMP."}
{"id": "PMID:218786", "title": "Triiodothyronine nuclear binding in fetal and adult rabbit lung and cultured lung cells.", "content": "To investigate the possible mechanism of thyroid hormone action in the lung, we examined fetal and adult rabbit lung, and cell lines derived from lung, for specific nuclear binding sites for T3. Using incubation of isolated nuclei with L-[125I]T3 at 37 C, we found approximately 2400 specific binding sites/cell in fetal lung and 1120 sites/cell in adult lung, with a similar dissociation constant (approximately 500 pm) for both tissues. The L-2 and A549 cell lines, which may have originated from pulmonary type II alveolar cells, contained 2280 and 1580 nuclear sites/cell, and the dissociation constants were 280 and 200 pm, respectively. In fetal lung, the ability of various analogs to compete for L-T3 (100%) binding was: 3,5-diiodo-3'-isopropylthyronine, 81%; D-T3, 73%; L-T4, 6.7%; 3,3'-diiodothyronine, 0.19%; 3,5-dimethyl-3'-isopropyl-L-thyronine, 0.15%; and rT3, 0.08%. These findings indicate that both fetal and adult lung, and cultured lung cells, contain specific nuclear binding sites for T3, suggesting that these tissues and their type II alveolar cells may be directly influenced by thyroid hormones.", "contents": "Triiodothyronine nuclear binding in fetal and adult rabbit lung and cultured lung cells. To investigate the possible mechanism of thyroid hormone action in the lung, we examined fetal and adult rabbit lung, and cell lines derived from lung, for specific nuclear binding sites for T3. Using incubation of isolated nuclei with L-[125I]T3 at 37 C, we found approximately 2400 specific binding sites/cell in fetal lung and 1120 sites/cell in adult lung, with a similar dissociation constant (approximately 500 pm) for both tissues. The L-2 and A549 cell lines, which may have originated from pulmonary type II alveolar cells, contained 2280 and 1580 nuclear sites/cell, and the dissociation constants were 280 and 200 pm, respectively. In fetal lung, the ability of various analogs to compete for L-T3 (100%) binding was: 3,5-diiodo-3'-isopropylthyronine, 81%; D-T3, 73%; L-T4, 6.7%; 3,3'-diiodothyronine, 0.19%; 3,5-dimethyl-3'-isopropyl-L-thyronine, 0.15%; and rT3, 0.08%. These findings indicate that both fetal and adult lung, and cultured lung cells, contain specific nuclear binding sites for T3, suggesting that these tissues and their type II alveolar cells may be directly influenced by thyroid hormones."}
{"id": "PMID:218787", "title": "Thyroid plasma membrane-associated protein kinases: properties and substrates of solubilized and insoluble enzymes.", "content": "The protein kinase activities of thyroid plasma membranes were characterized after treatment by the nonionic detergent, Triton X-100. With endogenous substrate the protein kinase activity of intact plasma membranes appeared to be cAMP independent, whereas the solubilized plasma membranes contained a cAMP-dependent protein kinase. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of intact plasma membranes demonstrated approximately 30 protein bands, of which several were substrates for endogenous protein kinase, cAMP had a slight, but reproducible, stimulatory effect on some of these. In solubilized plasma membranes cAMP significantly augmented phosphorylation of at least seven of these proteins. Solubilized plasma membranes bound significantly more cAMP per mg protein than intact plasma membranes. The inability to unequivocally detect cAMP-dependent protein kinase in intact membranes using endogenous substrate probably reflects the much greater activity of the cAMP-independent enzyme activity. The protein kinase activity of intact plasma membranes which was stimulated by cAMP when histone was the substrate was primarily recovered in the solubilized plasma membranes. Most of the protein kinase activity of the intact plasma membranes was insoluble and was not augmented by cAMP. The solubilized protein kinase demonstrated the same Km values for ATP, cAMP, and MgCl2 as did the cytosolic protein kinase of the thyroid. Cytosolic and solubilized protein kinase activities were more sensitive to cAMP and cGMP stimulation when histone and protamine were used as substrates. Both enzyme activities were depressed by protein kinase modulator when histone, but not protamine and casein, were used as substrates. The protein kinase activity of insoluble plasma membranes was not inhibited by the protein kinase modulator.", "contents": "Thyroid plasma membrane-associated protein kinases: properties and substrates of solubilized and insoluble enzymes. The protein kinase activities of thyroid plasma membranes were characterized after treatment by the nonionic detergent, Triton X-100. With endogenous substrate the protein kinase activity of intact plasma membranes appeared to be cAMP independent, whereas the solubilized plasma membranes contained a cAMP-dependent protein kinase. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of intact plasma membranes demonstrated approximately 30 protein bands, of which several were substrates for endogenous protein kinase, cAMP had a slight, but reproducible, stimulatory effect on some of these. In solubilized plasma membranes cAMP significantly augmented phosphorylation of at least seven of these proteins. Solubilized plasma membranes bound significantly more cAMP per mg protein than intact plasma membranes. The inability to unequivocally detect cAMP-dependent protein kinase in intact membranes using endogenous substrate probably reflects the much greater activity of the cAMP-independent enzyme activity. The protein kinase activity of intact plasma membranes which was stimulated by cAMP when histone was the substrate was primarily recovered in the solubilized plasma membranes. Most of the protein kinase activity of the intact plasma membranes was insoluble and was not augmented by cAMP. The solubilized protein kinase demonstrated the same Km values for ATP, cAMP, and MgCl2 as did the cytosolic protein kinase of the thyroid. Cytosolic and solubilized protein kinase activities were more sensitive to cAMP and cGMP stimulation when histone and protamine were used as substrates. Both enzyme activities were depressed by protein kinase modulator when histone, but not protamine and casein, were used as substrates. The protein kinase activity of insoluble plasma membranes was not inhibited by the protein kinase modulator."}
{"id": "PMID:218788", "title": "Steroid induction of gonadotropin surges in the immature rat. I. Priming effects of androgens.", "content": "Sexually immature female rats were either primed with estradiol benzoate on day 23 or given daily injections of various androgens on days 23--25. Plasma for LH and FSH determinations was collected on day 26, 5 h after an injection of progesterone. Massive gonadotropin surges were found after priming with estradiol benzoate or treatment with dehydroepiandrosterone (DHEA), delta 4-androstenedione, and testosterone, but not with ring A-reduced androgens (5 alpha-dihydrotestosterone, 5 alpha-androstane-3 alpha,17 beta-diol, its 3 beta-epimer, and androsterone) or the nonaromatizable 11 beta-hydroxy- and 11-ketoderivatives of delta 4-androstenedione. Rats bearing DHEA-containing Silastic implants also produced LH surges in response to progesterone. A single injection of an antiestrogen antiserum abolished gonadotropin surges in rats primed with estradiol benzoate or DHEA and greatly reduced the accompanying uterine hypertrophy. DHEA and delta 4-androstenedione were barely uterotrophic in ovariectomized rats but sustained progesterone-induced gonadotropin surges. The results indicate that certain (adrenal?) androgens are able to induce maturation of the steroid-sensitive surge system via extragonadal aromatization, whereas their uterotrophic effect is largely mediated by the ovaries. Coordinated increased conversion of androgens at central and peripheral sites may be of physiological importance for the triggering of puberty.", "contents": "Steroid induction of gonadotropin surges in the immature rat. I. Priming effects of androgens. Sexually immature female rats were either primed with estradiol benzoate on day 23 or given daily injections of various androgens on days 23--25. Plasma for LH and FSH determinations was collected on day 26, 5 h after an injection of progesterone. Massive gonadotropin surges were found after priming with estradiol benzoate or treatment with dehydroepiandrosterone (DHEA), delta 4-androstenedione, and testosterone, but not with ring A-reduced androgens (5 alpha-dihydrotestosterone, 5 alpha-androstane-3 alpha,17 beta-diol, its 3 beta-epimer, and androsterone) or the nonaromatizable 11 beta-hydroxy- and 11-ketoderivatives of delta 4-androstenedione. Rats bearing DHEA-containing Silastic implants also produced LH surges in response to progesterone. A single injection of an antiestrogen antiserum abolished gonadotropin surges in rats primed with estradiol benzoate or DHEA and greatly reduced the accompanying uterine hypertrophy. DHEA and delta 4-androstenedione were barely uterotrophic in ovariectomized rats but sustained progesterone-induced gonadotropin surges. The results indicate that certain (adrenal?) androgens are able to induce maturation of the steroid-sensitive surge system via extragonadal aromatization, whereas their uterotrophic effect is largely mediated by the ovaries. Coordinated increased conversion of androgens at central and peripheral sites may be of physiological importance for the triggering of puberty."}
{"id": "PMID:218789", "title": "Steroid induction of gonadotropin surges in the immature rat. II. Triggering ability of progesterone metabolites, adrenocortical hormones, and adrenocorticotropin.", "content": "Several adrenocortical steroids were tested for their ability to trigger LH release in estrogen-primed sexually immature female rats. Massive LH surges, approaching these known to be triggered by progesterone (P), followed the injection of depot ACTH1-24 and also of the adrenal steroids deoxycorticosterone (DOC) and 4-pregnen-21-ol-3,20-dione 21-acetate, but not of 5 alpha- and 5 beta-pregnan-21-of-3,20-dione, corticosterone, or aldosterone. Estrogen-primed adrenalectomized/ovariectomized rats also responded to DOC, albeit to a lesser extent. The P metabolites 5 alpha-pregnana-3,20-dione, 4-pregnen-20 alpha-ol-3-one, and 3 alpha-hydroxy-5 alpha-pregnan-20-one proved ineffective, although their triggering ability in adults was confirmed. It is concluded that adrenal P and DOC are potent activators of the gonadotropin surge system underlying pubertal ovulation and that P metabolites may acquire biological properties during sexual maturation.", "contents": "Steroid induction of gonadotropin surges in the immature rat. II. Triggering ability of progesterone metabolites, adrenocortical hormones, and adrenocorticotropin. Several adrenocortical steroids were tested for their ability to trigger LH release in estrogen-primed sexually immature female rats. Massive LH surges, approaching these known to be triggered by progesterone (P), followed the injection of depot ACTH1-24 and also of the adrenal steroids deoxycorticosterone (DOC) and 4-pregnen-21-ol-3,20-dione 21-acetate, but not of 5 alpha- and 5 beta-pregnan-21-of-3,20-dione, corticosterone, or aldosterone. Estrogen-primed adrenalectomized/ovariectomized rats also responded to DOC, albeit to a lesser extent. The P metabolites 5 alpha-pregnana-3,20-dione, 4-pregnen-20 alpha-ol-3-one, and 3 alpha-hydroxy-5 alpha-pregnan-20-one proved ineffective, although their triggering ability in adults was confirmed. It is concluded that adrenal P and DOC are potent activators of the gonadotropin surge system underlying pubertal ovulation and that P metabolites may acquire biological properties during sexual maturation."}
{"id": "PMID:218790", "title": "Extrapituitary regulation of the circadian rhythm of plasma corticosteroid concentration in rats.", "content": "Intravascular injections of adrenocorticotropic hormone in hypophysectomized rats were approximately 3 times more effective in stimulating increases in plasma corticosteroid concentration when given at the offset rather than the onset of the daily photoperiod (12 h:12 h light-dark cycle). Reversal of the photoperiodic schedule produced a reversal in the corticosteroid response after 5 days. Similar temporal variations in androgen and T4 responses to LH and TSH were not obtained. Although plasma corticosteroid concentrations were maintained at normal intermediate levels in rats with adrenal autotransplants, daily variations were not demonstrable. These results indicate that the circadian rhythm of plasma corticosteroid concentration is regulated by way of neural pathways to the adrenal.", "contents": "Extrapituitary regulation of the circadian rhythm of plasma corticosteroid concentration in rats. Intravascular injections of adrenocorticotropic hormone in hypophysectomized rats were approximately 3 times more effective in stimulating increases in plasma corticosteroid concentration when given at the offset rather than the onset of the daily photoperiod (12 h:12 h light-dark cycle). Reversal of the photoperiodic schedule produced a reversal in the corticosteroid response after 5 days. Similar temporal variations in androgen and T4 responses to LH and TSH were not obtained. Although plasma corticosteroid concentrations were maintained at normal intermediate levels in rats with adrenal autotransplants, daily variations were not demonstrable. These results indicate that the circadian rhythm of plasma corticosteroid concentration is regulated by way of neural pathways to the adrenal."}
{"id": "PMID:218792", "title": "Mitochondrial binding sites for triiodothyronine.", "content": "Metabolic effects upon rat liver mitochondria have been observed by others within 2 min of injection of massive amounts of L-T4. Reported here is the subcellular distribution of 2--5 ng high specific activity [125I]L-T3 2 min after ip injection with and without a loading dose of 30 micrograms unlabeled T3. The loading dose did not change the hormone concentration in the livers of normal or thyroidectomized rats, but it decreased the amount of hormone found in the nuclei in both groups and it increased the mitochondrial hormone only in the normals. The amounts of hormone in the nuclear and mitochondrial fractions were considerably higher in hypothyroid animals than in normals. By chromatography, over 90% of mitochondrial 125I was T3. The 125I content of Triton X-100 extracts of mitochondrial membranes was not affected by stable T3 in vivo or in vitro. It was concluded that specific high affinity, low capacity mitochondrial binding sites could not be found 2 min after hormone injection when specific nuclear binding sites are already evident. Specific binding may not be essential for the rapid effects of thyroid hormones upon rat liver mitochondria.", "contents": "Mitochondrial binding sites for triiodothyronine. Metabolic effects upon rat liver mitochondria have been observed by others within 2 min of injection of massive amounts of L-T4. Reported here is the subcellular distribution of 2--5 ng high specific activity [125I]L-T3 2 min after ip injection with and without a loading dose of 30 micrograms unlabeled T3. The loading dose did not change the hormone concentration in the livers of normal or thyroidectomized rats, but it decreased the amount of hormone found in the nuclei in both groups and it increased the mitochondrial hormone only in the normals. The amounts of hormone in the nuclear and mitochondrial fractions were considerably higher in hypothyroid animals than in normals. By chromatography, over 90% of mitochondrial 125I was T3. The 125I content of Triton X-100 extracts of mitochondrial membranes was not affected by stable T3 in vivo or in vitro. It was concluded that specific high affinity, low capacity mitochondrial binding sites could not be found 2 min after hormone injection when specific nuclear binding sites are already evident. Specific binding may not be essential for the rapid effects of thyroid hormones upon rat liver mitochondria."}
{"id": "PMID:218794", "title": "Some effects of adrenalectomy in the fatty rat.", "content": "Function of the pituitary-adrenal axis was examined in lean and genetically obese fatty (Zucker) rats. The diurnal rhythms of plasma corticosterone and plasma ACTH were similar in both groups. The secretion of corticosterone by adrenal glands incubated in vitro with graded doses of ACTH was also comparable in lean and fatty rats. Adrenalectomy reduced food intake and weight gain in the fatty rats to levels similar to those in the lean animals and raised plasma ACTH to the same level. The injection of corticosterone (2 and 10 mg/day) increased food intake more in adrenalectomized fatty rats than in the corresponding lean ones. Progesterone increased food intake similarly in both groups. The enhanced responsiveness to corticosterone could account for many of the metabolical defects in the fatty rat.", "contents": "Some effects of adrenalectomy in the fatty rat. Function of the pituitary-adrenal axis was examined in lean and genetically obese fatty (Zucker) rats. The diurnal rhythms of plasma corticosterone and plasma ACTH were similar in both groups. The secretion of corticosterone by adrenal glands incubated in vitro with graded doses of ACTH was also comparable in lean and fatty rats. Adrenalectomy reduced food intake and weight gain in the fatty rats to levels similar to those in the lean animals and raised plasma ACTH to the same level. The injection of corticosterone (2 and 10 mg/day) increased food intake more in adrenalectomized fatty rats than in the corresponding lean ones. Progesterone increased food intake similarly in both groups. The enhanced responsiveness to corticosterone could account for many of the metabolical defects in the fatty rat."}
{"id": "PMID:218798", "title": "Effect of gastrointestinal hormones on isolated bovine parathyroid cells.", "content": "The effects of gastrointestinal hormones on cAMP accumulation and parathyroid hormone (PTH) release were investigated in dispersed bovine parathyroid cells. Secretin (10 (-7) M) caused a 4- to 6-fold increase in cAMP accumulation, while glucagon, vasoactive intestinal peptide, and gastrin caused little if any stimulation. Cholecystokinin caused a 2- to 3-fold increase in cAMP accumulation at 10(-6) M, but this effect may be related to contamination with endogenous secretin since synthetic cholecystokinin octapeptide had no effect. Maximal intracellular cAMP accumulation due to 10(-7) M secretin was reached within 5 min and returned to control over the next 30-60 min, concomitant with a progressive rise in extracellular cyclic nucleotide. cAMP accumulation was half-maximally stimulated by 5 x 10(-9) to 1 x 10(-8) M secretin and was unaffected by alpha- or beta-adrenergic or dopaminergic blockers. Parallel effects were noted on PTH release : 10(-8) M secretin caused a 20-50% increment in PTH release at 15 min which persisted for up to 2 h; PTH release was stimulated half-maximally by approximately 6--8 x 10(-9) m secretin. The specificity of the observed results for secretin and the lack of effect of adrenergic antagonists suggest the presence of a receptor for secretin on dispersed bovine parathyroid cells. These results also suggest the possibility that secretin may modulate parathyroid function in vivo in the cow.", "contents": "Effect of gastrointestinal hormones on isolated bovine parathyroid cells. The effects of gastrointestinal hormones on cAMP accumulation and parathyroid hormone (PTH) release were investigated in dispersed bovine parathyroid cells. Secretin (10 (-7) M) caused a 4- to 6-fold increase in cAMP accumulation, while glucagon, vasoactive intestinal peptide, and gastrin caused little if any stimulation. Cholecystokinin caused a 2- to 3-fold increase in cAMP accumulation at 10(-6) M, but this effect may be related to contamination with endogenous secretin since synthetic cholecystokinin octapeptide had no effect. Maximal intracellular cAMP accumulation due to 10(-7) M secretin was reached within 5 min and returned to control over the next 30-60 min, concomitant with a progressive rise in extracellular cyclic nucleotide. cAMP accumulation was half-maximally stimulated by 5 x 10(-9) to 1 x 10(-8) M secretin and was unaffected by alpha- or beta-adrenergic or dopaminergic blockers. Parallel effects were noted on PTH release : 10(-8) M secretin caused a 20-50% increment in PTH release at 15 min which persisted for up to 2 h; PTH release was stimulated half-maximally by approximately 6--8 x 10(-9) m secretin. The specificity of the observed results for secretin and the lack of effect of adrenergic antagonists suggest the presence of a receptor for secretin on dispersed bovine parathyroid cells. These results also suggest the possibility that secretin may modulate parathyroid function in vivo in the cow."}
{"id": "PMID:218799", "title": "Purification and properties of 17 beta-hydroxy-C19-steroid dehydrogenases of adult male guinea pig kidney.", "content": "The 17 beta-hydroxy-C19-steroid dehydrogenase activity of adult male guinea pig kidney was separated into one isolated and two contiguous enzymatically pure fractions by submitting the cytosol to (NH4)2SO4 (40-80% saturation) precipitation, Sephadex G-75 filtration, and DEAE-Sephadex A-50 and CM-Sephadex C-50 chromatography. Further DEAE-Sephadex A-50 and CM-Sephadex C-50 chromatography separated eight isozymes, which were divided into four groups in accordance with their behavior on chromatography and mobility on gel electrophoresis. The molecular weights of the purified enzymes were identical by Sephadex filtration (33,000) and SDS gel electrophoresis (34,000). Two of the enzymes were separated by SDS gel electrophoresis into two subcomponents of 23,000 and 11,000 daltons. The amino acid composition, Km values, and coenzyme and substrate specificities of the enzymes (except one) were very similar. The pI values varied from 5.1-6.4 HgCl2 and PCMB inhibited enzyme activity, but prior addition of cysteine prevented the inhibition.  The presence of phosphate or pyrophosphate greatly enhanced the trace of DPN+ -linked activity. The heterogeneity was due to at least two factors. Rapid (within 3 h) preparation of the cytosol in 7 mM 2-mercaptoethanol yielded one intense and one minor enzyme band on gel electrophoresis. Omission of the mercaptoethanol resulted in the appearance of three enzyme bands, which were reversible on the addition of 2-mercaptoethanol. Storage of the cytosol at 4 or -20 C in the absence or presence of 7 mM 2-mercaptoethanol and of the kidney before extraction also resulted in the exhibition of enzyme bands which were not reversible on addition of 2-mercaptoethanol. The purified enzymes exhibited only a single form on storage at -20 C with 2-mercaptoethanol, but multiple forms appeared when the mercaptoethanol was removed by dialysis. The multiple forms were reverted to a single form on addition of mercaptoethanol.", "contents": "Purification and properties of 17 beta-hydroxy-C19-steroid dehydrogenases of adult male guinea pig kidney. The 17 beta-hydroxy-C19-steroid dehydrogenase activity of adult male guinea pig kidney was separated into one isolated and two contiguous enzymatically pure fractions by submitting the cytosol to (NH4)2SO4 (40-80% saturation) precipitation, Sephadex G-75 filtration, and DEAE-Sephadex A-50 and CM-Sephadex C-50 chromatography. Further DEAE-Sephadex A-50 and CM-Sephadex C-50 chromatography separated eight isozymes, which were divided into four groups in accordance with their behavior on chromatography and mobility on gel electrophoresis. The molecular weights of the purified enzymes were identical by Sephadex filtration (33,000) and SDS gel electrophoresis (34,000). Two of the enzymes were separated by SDS gel electrophoresis into two subcomponents of 23,000 and 11,000 daltons. The amino acid composition, Km values, and coenzyme and substrate specificities of the enzymes (except one) were very similar. The pI values varied from 5.1-6.4 HgCl2 and PCMB inhibited enzyme activity, but prior addition of cysteine prevented the inhibition.  The presence of phosphate or pyrophosphate greatly enhanced the trace of DPN+ -linked activity. The heterogeneity was due to at least two factors. Rapid (within 3 h) preparation of the cytosol in 7 mM 2-mercaptoethanol yielded one intense and one minor enzyme band on gel electrophoresis. Omission of the mercaptoethanol resulted in the appearance of three enzyme bands, which were reversible on the addition of 2-mercaptoethanol. Storage of the cytosol at 4 or -20 C in the absence or presence of 7 mM 2-mercaptoethanol and of the kidney before extraction also resulted in the exhibition of enzyme bands which were not reversible on addition of 2-mercaptoethanol. The purified enzymes exhibited only a single form on storage at -20 C with 2-mercaptoethanol, but multiple forms appeared when the mercaptoethanol was removed by dialysis. The multiple forms were reverted to a single form on addition of mercaptoethanol."}
{"id": "PMID:218800", "title": "Hormone receptors in livers of GH3 tumor-bearing rats: the predominant effect of growth hormone and testosterone.", "content": "The relationship between serum levels of rat GH (rGH), rat PRL (rPRL), corticosterone, estrogen, and testosterone and the liver-binding sites specific to [125I]iodo-human GH (hGH), -human PRL (hPRL), and -rPRL were investigated in normal rats, in rats bearing the GH- and PRL-secreting tumor (GH3), and in rats 14 days after tumor removal. The GH3 tumor elevated serum levels of rGH and rPRL and concomitantly increased the hepatic binding of radioiodinated hGH, hPRL, and rPRL; male rats had a greater increase than female rats. The increased binding was due to an increase in the specific membrane-binding sites, the receptors, whereas the affinity constant of binding (Ka) was not altered. In both male and female rats, the specific binding of receptors and the total binding capacities of livers correlated positively with serum levels of rGH (P less than 0.02) and inversely with serum levels of testosterone (P less than 0.05). There was insignificant or no correlation between rPRL or other steroids and the total liver-binding capacities. These results suggested that GH was the primary inducer and testosterone was the predominant regulator of the hepatic receptors in rats. The observed sex difference in the increase of receptors by GH3 tumor indicated that in normal and tumor-removed male rats, testosterone had suppressed the induction of hepatic receptors.", "contents": "Hormone receptors in livers of GH3 tumor-bearing rats: the predominant effect of growth hormone and testosterone. The relationship between serum levels of rat GH (rGH), rat PRL (rPRL), corticosterone, estrogen, and testosterone and the liver-binding sites specific to [125I]iodo-human GH (hGH), -human PRL (hPRL), and -rPRL were investigated in normal rats, in rats bearing the GH- and PRL-secreting tumor (GH3), and in rats 14 days after tumor removal. The GH3 tumor elevated serum levels of rGH and rPRL and concomitantly increased the hepatic binding of radioiodinated hGH, hPRL, and rPRL; male rats had a greater increase than female rats. The increased binding was due to an increase in the specific membrane-binding sites, the receptors, whereas the affinity constant of binding (Ka) was not altered. In both male and female rats, the specific binding of receptors and the total binding capacities of livers correlated positively with serum levels of rGH (P less than 0.02) and inversely with serum levels of testosterone (P less than 0.05). There was insignificant or no correlation between rPRL or other steroids and the total liver-binding capacities. These results suggested that GH was the primary inducer and testosterone was the predominant regulator of the hepatic receptors in rats. The observed sex difference in the increase of receptors by GH3 tumor indicated that in normal and tumor-removed male rats, testosterone had suppressed the induction of hepatic receptors."}
{"id": "PMID:218801", "title": "Suppression of aldosterone biosynthesis by treatment of rats with adrenocorticotropin: comparison with glucocorticoid effects.", "content": "The treatment of rats with a high dose of ACTH resulted within 4 days in a marked suppression of aldosterone and deoxycorticosterone outputs by capsular adrenal tissue (\"zona glomerulosa\") incubated with and without serotonin and in decreased conversions of tritiated corticosterone and deoxycorticosterone to aldosterone and 18-hydroxycorticosterone, but in strikingly increased capsular adrenal conversions of tritiated deoxycorticosterone to corticosterone and 18-hydroxy deoxycorticosterone. ACTH also suppressed aldosterone biosynthesis in rats kept on a sodium-deficient diet. Corticosterone or dexamethasone, when added to the drinking fluid for 2 weeks, induced only small decreases in aldosterone biosynthesis from endogenous or exogenous precursors. Moreover, they significantly decreased the capsular adrenal conversion of added deoxycorticosterone to corticosterone and 18-hydroxydeoxycorticosterone. These results indicate that during prolonged ACTH treatment, the zona glomerulosa cell may be converted to a functional zona fasciculata type of cell. High levels of circulating mineralocorticoids and glucocorticoids seem to be minor contributory factors in the long term suppression of aldosterone biosynthesis by ACTH.", "contents": "Suppression of aldosterone biosynthesis by treatment of rats with adrenocorticotropin: comparison with glucocorticoid effects. The treatment of rats with a high dose of ACTH resulted within 4 days in a marked suppression of aldosterone and deoxycorticosterone outputs by capsular adrenal tissue (\"zona glomerulosa\") incubated with and without serotonin and in decreased conversions of tritiated corticosterone and deoxycorticosterone to aldosterone and 18-hydroxycorticosterone, but in strikingly increased capsular adrenal conversions of tritiated deoxycorticosterone to corticosterone and 18-hydroxy deoxycorticosterone. ACTH also suppressed aldosterone biosynthesis in rats kept on a sodium-deficient diet. Corticosterone or dexamethasone, when added to the drinking fluid for 2 weeks, induced only small decreases in aldosterone biosynthesis from endogenous or exogenous precursors. Moreover, they significantly decreased the capsular adrenal conversion of added deoxycorticosterone to corticosterone and 18-hydroxydeoxycorticosterone. These results indicate that during prolonged ACTH treatment, the zona glomerulosa cell may be converted to a functional zona fasciculata type of cell. High levels of circulating mineralocorticoids and glucocorticoids seem to be minor contributory factors in the long term suppression of aldosterone biosynthesis by ACTH."}
{"id": "PMID:218802", "title": "Prolactin, growth hormone, luteinizing hormone receptors, and seasonal changes in testicular activity in the golden hamster.", "content": "In adult male hamsters, 2 months of exposure to a short photoperiod (5 h of light:19 h of darkness) caused testicular regression and a precipitous decline in plasma PRL, in agreement with earlier reports from other laboratories. Depressed release of PRL cannot be explained by a reduction in testicular steroidogenesis, because castration of males kept in a long photoperiod did not reduce PRL levels and administration of testosterone to males kept in a short photoperiod failed to reverse the decline in plasma PRL concentration. Treatment of such \"regressed\" animals with PRL, GH, or ectopic pituitary transplants stimulated growth of the testes and the accessory reproductive glands, increased the concentration of LH receptors in the testes, and elevated plasma testosterone levels. A single injection of 250 microgram PRL was sufficient to increase testicular LH binding, and chronic treatment with pituitary grafts completely reversed testicular regression. The effectiveness of exogenous PRL in stimulating testicular growth and LH receptors was significantly influenced by the timing of the injection. In some experiments, gonadotropin levels appeared elevated in animals injected with PRL, but these differences were not statistically significant. In hamsters with gonadal regression induced by exposure to a short photoperiod, daily administration of 20 microgram H and/or 150 microgram FSH had no apparent effect on testicular function. However, treatment with large doses of hCG and/or PMS gonadotropin resulted in significant stimulation of testicular growth and steroidogenesis. Chronic treatment of males maintained in a long photoperiod (14 h of light:10 h of darkness) with an inhibitor of PRL release, 2-Br-alpha-ergocryptine, resulted in a decreased weight of the testes and seminal vesicles. Administration of this inhibitor for a longer period (2 months) produced a significant increase in body weight but had little effect on testicular function. These results indicate that changes in the release of PRL (and possibly also GH) may plan an important role in mediating the effects of the photoperiod on testicular function in the golden hamster.", "contents": "Prolactin, growth hormone, luteinizing hormone receptors, and seasonal changes in testicular activity in the golden hamster. In adult male hamsters, 2 months of exposure to a short photoperiod (5 h of light:19 h of darkness) caused testicular regression and a precipitous decline in plasma PRL, in agreement with earlier reports from other laboratories. Depressed release of PRL cannot be explained by a reduction in testicular steroidogenesis, because castration of males kept in a long photoperiod did not reduce PRL levels and administration of testosterone to males kept in a short photoperiod failed to reverse the decline in plasma PRL concentration. Treatment of such \"regressed\" animals with PRL, GH, or ectopic pituitary transplants stimulated growth of the testes and the accessory reproductive glands, increased the concentration of LH receptors in the testes, and elevated plasma testosterone levels. A single injection of 250 microgram PRL was sufficient to increase testicular LH binding, and chronic treatment with pituitary grafts completely reversed testicular regression. The effectiveness of exogenous PRL in stimulating testicular growth and LH receptors was significantly influenced by the timing of the injection. In some experiments, gonadotropin levels appeared elevated in animals injected with PRL, but these differences were not statistically significant. In hamsters with gonadal regression induced by exposure to a short photoperiod, daily administration of 20 microgram H and/or 150 microgram FSH had no apparent effect on testicular function. However, treatment with large doses of hCG and/or PMS gonadotropin resulted in significant stimulation of testicular growth and steroidogenesis. Chronic treatment of males maintained in a long photoperiod (14 h of light:10 h of darkness) with an inhibitor of PRL release, 2-Br-alpha-ergocryptine, resulted in a decreased weight of the testes and seminal vesicles. Administration of this inhibitor for a longer period (2 months) produced a significant increase in body weight but had little effect on testicular function. These results indicate that changes in the release of PRL (and possibly also GH) may plan an important role in mediating the effects of the photoperiod on testicular function in the golden hamster."}
{"id": "PMID:218804", "title": "Prolactin induces its own receptors in rat liver.", "content": "Attempts to restore PRL receptors (PRL-R) in liver membranes of hypophysectomized rats with injections of PRL have so far been only partly successful. In the present study, bovine PRL (bPRL) was mixed with polyvinylpyrrolidone (PVP) in order to sustain PRL blood levels with a single injection a day. PRL-R were measured by displacement of the binding of [125I]ovine PRL (lactoperoxidase oxidation) to a 5000 x g particulate fraction of liver by unlabeled ovine PRL. The number of binding sites was calculated by Scatchard analysis and expressed as femtomoles per mg protein. PRL-R were 85 +/- 12 fmol/mg in normal intact female rats. Seven days posthypophysectomy, PRL-R were undetectable. Daily injections of bPRL with PVP for 10 days fully restored  PRL-R (117 +/- 32 fmol/mg). No significant change in PRL-R was noted when bPRL was injected with bovine GH (bGH; 120 +/- 23 fmol/mg), bovine LH (bLH; 84 +/- 14 fmol/mg), bGH plus bLH (90 +/- 12 fmol/mg), or estrogens (79 +/- 12 fmol/mg). Daily injections of bGH or bLH, alone or in combination, or estrogens with PVP failed to restore PRL-R. These results demonstrate a direct role of PRL in stimulating the production of its own receptors when a sustained blood level of the hormone is achieved.", "contents": "Prolactin induces its own receptors in rat liver. Attempts to restore PRL receptors (PRL-R) in liver membranes of hypophysectomized rats with injections of PRL have so far been only partly successful. In the present study, bovine PRL (bPRL) was mixed with polyvinylpyrrolidone (PVP) in order to sustain PRL blood levels with a single injection a day. PRL-R were measured by displacement of the binding of [125I]ovine PRL (lactoperoxidase oxidation) to a 5000 x g particulate fraction of liver by unlabeled ovine PRL. The number of binding sites was calculated by Scatchard analysis and expressed as femtomoles per mg protein. PRL-R were 85 +/- 12 fmol/mg in normal intact female rats. Seven days posthypophysectomy, PRL-R were undetectable. Daily injections of bPRL with PVP for 10 days fully restored  PRL-R (117 +/- 32 fmol/mg). No significant change in PRL-R was noted when bPRL was injected with bovine GH (bGH; 120 +/- 23 fmol/mg), bovine LH (bLH; 84 +/- 14 fmol/mg), bGH plus bLH (90 +/- 12 fmol/mg), or estrogens (79 +/- 12 fmol/mg). Daily injections of bGH or bLH, alone or in combination, or estrogens with PVP failed to restore PRL-R. These results demonstrate a direct role of PRL in stimulating the production of its own receptors when a sustained blood level of the hormone is achieved."}
{"id": "PMID:218805", "title": "The effect of adrenocorticotropin and nucleotides on Ca2+ uptake in adrenal cortical microsomal vesicles.", "content": "Rat and bovine adrenal cortical microsomal fractions isolated at 27,000 x g and 105,000 x g accumulated Ca2+ by a nonmitochondrial, ATP-dependent uptake system that was stimulated by ammonium oxalate. ACTH (2 mU/ml) significantly increased Ca2+ uptake in bovine adrenal cortical microsomes and in adrenal microsomes from acutely hypophysectomized rats, but only when the hormone was preincubated with intact tissue and not when it was added after homogenization. ACTH did not stimulate C2+ uptake in adrenal microsomes isolated from nonhypophysectomized, ether-stressed rats, in which basal Ca2+ uptake was higher than that observed in microsomes from hypophysectomized animals. The peptides oxytocin, insulin, and TSH did not stimulate Ca2+ uptake by adrenal cortical microsomes. ACTH preincubated with intact tissue had no effect on Ca2+ uptake in microsomes from liver, kidney, esophagus, or aorta. cAMP, 5'-AMP, and several other nucleotides, nucleosides, and related compounds stimulated adrenal cortical microsomal Ca2+ uptake by as much as 540% of control. The stimulatory effects of nucleotides, unlike those of ACTH, were apparent even when the agents were added after homogenization. However, like ACTH, the nucleotides were unable to stimulate Ca2+ uptake when they were added to isolated membrane vesicles during Ca2+ uptake measurements. It is suggested that the microsomal Ca2+ uptake system may respond to physiological stimulants and regulate Ca2+ availability in the intact cell.", "contents": "The effect of adrenocorticotropin and nucleotides on Ca2+ uptake in adrenal cortical microsomal vesicles. Rat and bovine adrenal cortical microsomal fractions isolated at 27,000 x g and 105,000 x g accumulated Ca2+ by a nonmitochondrial, ATP-dependent uptake system that was stimulated by ammonium oxalate. ACTH (2 mU/ml) significantly increased Ca2+ uptake in bovine adrenal cortical microsomes and in adrenal microsomes from acutely hypophysectomized rats, but only when the hormone was preincubated with intact tissue and not when it was added after homogenization. ACTH did not stimulate C2+ uptake in adrenal microsomes isolated from nonhypophysectomized, ether-stressed rats, in which basal Ca2+ uptake was higher than that observed in microsomes from hypophysectomized animals. The peptides oxytocin, insulin, and TSH did not stimulate Ca2+ uptake by adrenal cortical microsomes. ACTH preincubated with intact tissue had no effect on Ca2+ uptake in microsomes from liver, kidney, esophagus, or aorta. cAMP, 5'-AMP, and several other nucleotides, nucleosides, and related compounds stimulated adrenal cortical microsomal Ca2+ uptake by as much as 540% of control. The stimulatory effects of nucleotides, unlike those of ACTH, were apparent even when the agents were added after homogenization. However, like ACTH, the nucleotides were unable to stimulate Ca2+ uptake when they were added to isolated membrane vesicles during Ca2+ uptake measurements. It is suggested that the microsomal Ca2+ uptake system may respond to physiological stimulants and regulate Ca2+ availability in the intact cell."}
{"id": "PMID:218806", "title": "Thyroid hormone modulation of epinephrine-induced lipolysis in rat adipocytes: a possible role of calcium.", "content": "Adipocytes isolated from normal, hypothyroid, and hyperthyroid rats were characterized with respect to their lipolytic activity (assessed by glycerol release) and beta-adrenergic receptors (assessed by binding of (--) [3H]alprenolol). Fat cells from hypo- and hyperthyroid rats showed the same affinity (K = 1.4 X 10(10) M(-1) and binding capacity (N = 1.21 X 10(-13) mol/microgram DNA) toward alprenolol as those from normal animals. Adipocytes from hypothyroid rats were unresponsive to epinephrine in a concentration range of 0.1-10 micron, with moderate responses at higher concentrations; injection of T3 in hypothyroid rats restored lipolytic responsiveness of the adipocytes to normal levels. Quabain (1 mM) inhibited lipolytic responses to epinephrine by 40--45% in normal and hyperthyroid rats; the lipolytic increment due to the hyperthyroid state was uninfluenced by ouabain. The lipolytic refractoriness to epinephrine of hypothyroid adipocytes was restored to normal levels by theophylline (1 mM) or EGTA  (1 mM); the theophylline and EGTA effects were not additive, suggesting that they stimulated lipolysis via a common mechanism. Epinephrine-induced lipolysis in all groups was progressively inhibited by increasing concentrations of Ca2+ in the medium. The Ca ionophore, A23187, showed a concentration-dependent inhibitory action. Theophylline (1mM) almost completely overcame the inhibitory action of the ionophore; in the presence of lower concentrations of theophylline, the inhibitory effect of the ionophore was least in hypothyroid and greatest in hyperthyroid fat cells. The findings suggest that the differences in the lipolytic response to epinephrine observed in hyperthyroid, euthyroid, and hypothyroid adipocytes are not due to alterations in the number or affinity of beta-adrenergic receptors nor to a membrane mechanism that might show differential ouabain sensitivity, but may be related to altered cellular Ca2+ concentrations which may indirectly alter cellular phosphodiesterase activity.", "contents": "Thyroid hormone modulation of epinephrine-induced lipolysis in rat adipocytes: a possible role of calcium. Adipocytes isolated from normal, hypothyroid, and hyperthyroid rats were characterized with respect to their lipolytic activity (assessed by glycerol release) and beta-adrenergic receptors (assessed by binding of (--) [3H]alprenolol). Fat cells from hypo- and hyperthyroid rats showed the same affinity (K = 1.4 X 10(10) M(-1) and binding capacity (N = 1.21 X 10(-13) mol/microgram DNA) toward alprenolol as those from normal animals. Adipocytes from hypothyroid rats were unresponsive to epinephrine in a concentration range of 0.1-10 micron, with moderate responses at higher concentrations; injection of T3 in hypothyroid rats restored lipolytic responsiveness of the adipocytes to normal levels. Quabain (1 mM) inhibited lipolytic responses to epinephrine by 40--45% in normal and hyperthyroid rats; the lipolytic increment due to the hyperthyroid state was uninfluenced by ouabain. The lipolytic refractoriness to epinephrine of hypothyroid adipocytes was restored to normal levels by theophylline (1 mM) or EGTA  (1 mM); the theophylline and EGTA effects were not additive, suggesting that they stimulated lipolysis via a common mechanism. Epinephrine-induced lipolysis in all groups was progressively inhibited by increasing concentrations of Ca2+ in the medium. The Ca ionophore, A23187, showed a concentration-dependent inhibitory action. Theophylline (1mM) almost completely overcame the inhibitory action of the ionophore; in the presence of lower concentrations of theophylline, the inhibitory effect of the ionophore was least in hypothyroid and greatest in hyperthyroid fat cells. The findings suggest that the differences in the lipolytic response to epinephrine observed in hyperthyroid, euthyroid, and hypothyroid adipocytes are not due to alterations in the number or affinity of beta-adrenergic receptors nor to a membrane mechanism that might show differential ouabain sensitivity, but may be related to altered cellular Ca2+ concentrations which may indirectly alter cellular phosphodiesterase activity."}
{"id": "PMID:218807", "title": "Decreased hepatic nuclear L-triiodothyronine receptors in rats and mice bearing transplantable neoplasms.", "content": "The concentration of hepatic nuclear T3 receptors was measured in isolated nuclei from athyreotic mice bearing thyrotrophic tumors and intact rats with Walker 256 carcinoma. Receptor concentration was reduced in all tumor-bearing animals. The mean receptor capacity of the Walker tumor-bearing rats [0.31 +/- 0.05 (SEM) ng/mg DNA] was significantly decreased from simultaneously assayed controls (0.47 +/- 0.04 ng/mg DNA; P less than 0.01). No change in the apparent equilibrium association constant was observed. In individual rats, the magnitude of the decrease in nuclear T3 receptor concentration was highly correlated with the decrease in tumor-free body weight. Additional studies showed that the decrease in nuclear receptors was not due to delayed equilibration of added T3 with nuclear sites in vitro or to an increase in endogenous hepatic T3 concentration. The plasma concentration of total and free T4 and T3 was decreased in tumor-bearing rats. Plasma TSH concentration, however, remained unchanged. Thus, these transplantable neoplasms seem to be associated with decreased hepatic nuclear receptors and low concentrations of plasma thyroid hormones. The unchanged plasma TSH suggests that the animals remained euthyroid.", "contents": "Decreased hepatic nuclear L-triiodothyronine receptors in rats and mice bearing transplantable neoplasms. The concentration of hepatic nuclear T3 receptors was measured in isolated nuclei from athyreotic mice bearing thyrotrophic tumors and intact rats with Walker 256 carcinoma. Receptor concentration was reduced in all tumor-bearing animals. The mean receptor capacity of the Walker tumor-bearing rats [0.31 +/- 0.05 (SEM) ng/mg DNA] was significantly decreased from simultaneously assayed controls (0.47 +/- 0.04 ng/mg DNA; P less than 0.01). No change in the apparent equilibrium association constant was observed. In individual rats, the magnitude of the decrease in nuclear T3 receptor concentration was highly correlated with the decrease in tumor-free body weight. Additional studies showed that the decrease in nuclear receptors was not due to delayed equilibration of added T3 with nuclear sites in vitro or to an increase in endogenous hepatic T3 concentration. The plasma concentration of total and free T4 and T3 was decreased in tumor-bearing rats. Plasma TSH concentration, however, remained unchanged. Thus, these transplantable neoplasms seem to be associated with decreased hepatic nuclear receptors and low concentrations of plasma thyroid hormones. The unchanged plasma TSH suggests that the animals remained euthyroid."}
{"id": "PMID:218808", "title": "Time course of thyrotropin-dependent protein phosphorylation in thyroid slices.", "content": "The time course of TSH-dependent protein phosphorylation was studied in calf thyroid slices labeled in vitro with 32Pi. Several of the proteins identified by two-dimensional electrophoresis displayed striking increases in 32P labeling in the presence of TSH. Phosphorylation of histones H3 and H1 (two subgroups) was enhanced about 3.7-and 10-fold, respectively, after incubation with TSH (15 mu/ml) for 70 min. Histone phosphorylation showed a lag after exposure to TSH; a major increase occurred only after 30-min incubation but then increased progressively up to 2 h. The lag in histone phosphorylation was also observed with slices prelabeled with 32P before the addition of TSH. In contrast, phosphorylation of a minor basic protein, A5 was also increased by 15 mU/ml TSH but displayed different kinetics, increasing substantially at 10 min. This time course correlates well with the rise in intracellular cAMP levels and protein kinase activity in thyroid slices after TSH.", "contents": "Time course of thyrotropin-dependent protein phosphorylation in thyroid slices. The time course of TSH-dependent protein phosphorylation was studied in calf thyroid slices labeled in vitro with 32Pi. Several of the proteins identified by two-dimensional electrophoresis displayed striking increases in 32P labeling in the presence of TSH. Phosphorylation of histones H3 and H1 (two subgroups) was enhanced about 3.7-and 10-fold, respectively, after incubation with TSH (15 mu/ml) for 70 min. Histone phosphorylation showed a lag after exposure to TSH; a major increase occurred only after 30-min incubation but then increased progressively up to 2 h. The lag in histone phosphorylation was also observed with slices prelabeled with 32P before the addition of TSH. In contrast, phosphorylation of a minor basic protein, A5 was also increased by 15 mU/ml TSH but displayed different kinetics, increasing substantially at 10 min. This time course correlates well with the rise in intracellular cAMP levels and protein kinase activity in thyroid slices after TSH."}
{"id": "PMID:218809", "title": "Purification and characterization of the messenger RNA coding for bovine corticotropin/beta-lipotropin precursor.", "content": "The mRNA coding for the common precursor of corticotropin and beta-lipotropin has been purified to homogeneity from neurointermediate lobes of bovine pituitaries. The homogeneity of the mRNA preparation is evidenced by analysis of its translation product, electrophoresis on polyacrylamide gel in the presence of formamide and analysis of the kinetics of hybridization with its cDNA. The purification procedure involves the isolation of RNA from membrane-bound polysomes, chromatography on oligo(dT)-cellulose and on poly(U)-Sepharose and sucrose density gradient centrifugation. The mRNA has a molecular weight of approximately 450000, equivalent to approximately 1360 nucleotides in length, and contains a polyadenylate sequence with an average length of 68 nucleotides. The size of the mRNA is sufficiently large to encode the corticotropin/beta-lipotropin precursor.", "contents": "Purification and characterization of the messenger RNA coding for bovine corticotropin/beta-lipotropin precursor. The mRNA coding for the common precursor of corticotropin and beta-lipotropin has been purified to homogeneity from neurointermediate lobes of bovine pituitaries. The homogeneity of the mRNA preparation is evidenced by analysis of its translation product, electrophoresis on polyacrylamide gel in the presence of formamide and analysis of the kinetics of hybridization with its cDNA. The purification procedure involves the isolation of RNA from membrane-bound polysomes, chromatography on oligo(dT)-cellulose and on poly(U)-Sepharose and sucrose density gradient centrifugation. The mRNA has a molecular weight of approximately 450000, equivalent to approximately 1360 nucleotides in length, and contains a polyadenylate sequence with an average length of 68 nucleotides. The size of the mRNA is sufficiently large to encode the corticotropin/beta-lipotropin precursor."}
{"id": "PMID:218810", "title": "Brain pyridoxal kinase. Mobility of the substrate pyridoxal and binding of inhibitors to the nucleotide site.", "content": "Pyridoxal kinase has been purified 2000-fold from pig brain. The enzyme preparation migrates as a single protein and activity band on analytical gel electrophoresis. The interactions of the substrate pyridoxal and the inhibitor N-dansyl-2-oxopyrrolidine (dansyl = 5-dimethylaminonaphthalene-1-sulfonyl) with the catalytic site were examined by means of fluorescence spectroscopy. The increase in emission anisotropy that follows the binding of pyridoxal to the kinase was used to determine the equilibrium dissociation constant. Pyridoxal kinase binds one molecule of substrate with a Kd = 11 microns at pH 6. The emission anisotropy spectrum of bound pyridoxal reveals that the substrate is not rigidly trapped by the protein matrix. N-Dansyl-2-oxopyrrolidine is a competitive inhibitor with respect to ATP at saturating concentrations of pyridoxal. It binds to the enzyme with a dissociation constant of 6 microns. N-Dansyl-2-oxopyrrolidine is immobilized by strong interactions with the enzyme, but it is displaced from the catalytic site by ATP. The results are consistent with the hypothesis that N-dansyl-2-oxopyrrolidine binds at the nucleotide binding site of pyridoxal kinase.", "contents": "Brain pyridoxal kinase. Mobility of the substrate pyridoxal and binding of inhibitors to the nucleotide site. Pyridoxal kinase has been purified 2000-fold from pig brain. The enzyme preparation migrates as a single protein and activity band on analytical gel electrophoresis. The interactions of the substrate pyridoxal and the inhibitor N-dansyl-2-oxopyrrolidine (dansyl = 5-dimethylaminonaphthalene-1-sulfonyl) with the catalytic site were examined by means of fluorescence spectroscopy. The increase in emission anisotropy that follows the binding of pyridoxal to the kinase was used to determine the equilibrium dissociation constant. Pyridoxal kinase binds one molecule of substrate with a Kd = 11 microns at pH 6. The emission anisotropy spectrum of bound pyridoxal reveals that the substrate is not rigidly trapped by the protein matrix. N-Dansyl-2-oxopyrrolidine is a competitive inhibitor with respect to ATP at saturating concentrations of pyridoxal. It binds to the enzyme with a dissociation constant of 6 microns. N-Dansyl-2-oxopyrrolidine is immobilized by strong interactions with the enzyme, but it is displaced from the catalytic site by ATP. The results are consistent with the hypothesis that N-dansyl-2-oxopyrrolidine binds at the nucleotide binding site of pyridoxal kinase."}
{"id": "PMID:218811", "title": "Mechanism of carbamoyl-phosphate synthetase. Binding of ATP by the rat-liver mitochondrial enzyme.", "content": "This paper demonstrates, by pulse-chase techniques, the binding to rat liver mitochondrial carbamoyl phosphate synthetase of the ATP molecule (ATPB) which transfers its gamma-phosphoryl group to carbamoyl phosphate. This bound APTB can react with NH3, HCO-3 and ATP (see below) to produce carbamoyl phosphate before it exchanges with free ATP. Mg2+ and N-acetylglutamate, but not NH3 or HCO-3, are required for this binding; the amount bound depends on the concentration of ATP (Kapp = 10--30 microns ATP) and the amount of enzyme. At saturation at least one ATPB molecule binds per enzyme dimer. Binding of ATPB follows a slow exponential time course (t1/2 8--16 s, 22 degrees C), independent of ATP concentration and little affected by NH3, NCO-3 or by incubation of the enzyme with unlabelled ATP prior to the pulse of [gamma-32P]ATP. Formation of carbamoyl phosphate from traces of NH3 and HCO-3 when the enzyme is incubated with ATP follows the kinetics expected if it were generated from the bound ATPB, indicating that the latter is a precursor of carbamoyl phosphate ('Cbm-P precursor') in the normal enzyme reaction. This indicates that the site for ATPB is usually inaccessible to ATP in solution but becomes accessible when the enzyme undergoes a periodical conformational change. Bound ATP becomes Cbm-P precursor when the enzyme reverts to the inaccessible conformation. Pulse-chase experiments in the absence of NH3 and HCO-3 (less than 0.2 mM) also demonstrate binding of ATPA (the molecule which yields Pi in the normal enzyme reaction), as shown by a 'burst' in 32Pi production. Therefore, (in accordance with our previous findings) both ATPA and ATPB can bind simultaneously to the enzyme and react with NH3 and HCO-3 in the chase solution before they can exchange with free ATP. However, at low ATP concentration (18 micron) in the pulse incubation, only ATPB binds since ATP is required in the chase (see above). Despite the presence of two ATP binding sites, the bifunctional inhibitor adenosine(5')pentaphospho(5')adenosine(Ap5A) fails to inhibit the enzyme significantly. A more detailed modification of the scheme previously published [Rubio, V. & Grisolia, S. (1977) Biochemistry, 16, 321--329] is proposed; it is suggested that ATPB gains access to the active centre when the products leave the enzyme and the active centre is in an accessible configuration. The transformation from accessible to inaccessible configuration appears to be part of the normal enzyme reaction and may represent to conformational change postulated by others from steady-state kinetics. The properties of the intermediates also indicate that hydrolysis of ATPA must be largely responsible for the HCO-3-dependent ATPase activity of the enzyme. The lack of inhibition of the enzyme by Ap5A indicates substantial differences between the Escherichia coli and the rat liver synthetase.", "contents": "Mechanism of carbamoyl-phosphate synthetase. Binding of ATP by the rat-liver mitochondrial enzyme. This paper demonstrates, by pulse-chase techniques, the binding to rat liver mitochondrial carbamoyl phosphate synthetase of the ATP molecule (ATPB) which transfers its gamma-phosphoryl group to carbamoyl phosphate. This bound APTB can react with NH3, HCO-3 and ATP (see below) to produce carbamoyl phosphate before it exchanges with free ATP. Mg2+ and N-acetylglutamate, but not NH3 or HCO-3, are required for this binding; the amount bound depends on the concentration of ATP (Kapp = 10--30 microns ATP) and the amount of enzyme. At saturation at least one ATPB molecule binds per enzyme dimer. Binding of ATPB follows a slow exponential time course (t1/2 8--16 s, 22 degrees C), independent of ATP concentration and little affected by NH3, NCO-3 or by incubation of the enzyme with unlabelled ATP prior to the pulse of [gamma-32P]ATP. Formation of carbamoyl phosphate from traces of NH3 and HCO-3 when the enzyme is incubated with ATP follows the kinetics expected if it were generated from the bound ATPB, indicating that the latter is a precursor of carbamoyl phosphate ('Cbm-P precursor') in the normal enzyme reaction. This indicates that the site for ATPB is usually inaccessible to ATP in solution but becomes accessible when the enzyme undergoes a periodical conformational change. Bound ATP becomes Cbm-P precursor when the enzyme reverts to the inaccessible conformation. Pulse-chase experiments in the absence of NH3 and HCO-3 (less than 0.2 mM) also demonstrate binding of ATPA (the molecule which yields Pi in the normal enzyme reaction), as shown by a 'burst' in 32Pi production. Therefore, (in accordance with our previous findings) both ATPA and ATPB can bind simultaneously to the enzyme and react with NH3 and HCO-3 in the chase solution before they can exchange with free ATP. However, at low ATP concentration (18 micron) in the pulse incubation, only ATPB binds since ATP is required in the chase (see above). Despite the presence of two ATP binding sites, the bifunctional inhibitor adenosine(5')pentaphospho(5')adenosine(Ap5A) fails to inhibit the enzyme significantly. A more detailed modification of the scheme previously published [Rubio, V. & Grisolia, S. (1977) Biochemistry, 16, 321--329] is proposed; it is suggested that ATPB gains access to the active centre when the products leave the enzyme and the active centre is in an accessible configuration. The transformation from accessible to inaccessible configuration appears to be part of the normal enzyme reaction and may represent to conformational change postulated by others from steady-state kinetics. The properties of the intermediates also indicate that hydrolysis of ATPA must be largely responsible for the HCO-3-dependent ATPase activity of the enzyme. The lack of inhibition of the enzyme by Ap5A indicates substantial differences between the Escherichia coli and the rat liver synthetase."}
{"id": "PMID:218812", "title": "Mitochondrial GTP-AMP phosphotransferase. 1. Purification and properties.", "content": "GTP-AMP phosphotransferase has been purified 116-fold with a yield of 24% from beef heart mitochondria using freeze-thawing, alkali and acid treatment and successive column chromatography on phosphocellulose, Sephadex G-100 and blue-dextran--Sepharose. It has crystallized from poly-(ethylene glycol) and is essential homogeneous by sodium dodecylsulfate electrophoresis and isoelectrofocusing. The specific activity of the crystalline preparation was 290 U/mg. The molecular weight was found to be 26000 and the isoelectric point to be 9.8. Amino acid analysis showed 21 aspartic acid or asparagine, 19 threonine, 12 serine, 26 glutamic acid or glutamine, 15 proline, 16 glycine, 14 alanine, 15 valine, 4 methionine, 12 isoleucine, 28 leucine, 7 tyrosine, 7 phenylalanine, 5 histidine, 14 lysine, 16 arginine, 2 tryptophan, no --SS-- bonds or free --SH. Guanosine(5')pentaphospho(5')adenosine is a very strong inhibitor similar to adenosine(5')pentaphospho(5')adenosine as an inhibitor of cytosolic adenylate kinase.", "contents": "Mitochondrial GTP-AMP phosphotransferase. 1. Purification and properties. GTP-AMP phosphotransferase has been purified 116-fold with a yield of 24% from beef heart mitochondria using freeze-thawing, alkali and acid treatment and successive column chromatography on phosphocellulose, Sephadex G-100 and blue-dextran--Sepharose. It has crystallized from poly-(ethylene glycol) and is essential homogeneous by sodium dodecylsulfate electrophoresis and isoelectrofocusing. The specific activity of the crystalline preparation was 290 U/mg. The molecular weight was found to be 26000 and the isoelectric point to be 9.8. Amino acid analysis showed 21 aspartic acid or asparagine, 19 threonine, 12 serine, 26 glutamic acid or glutamine, 15 proline, 16 glycine, 14 alanine, 15 valine, 4 methionine, 12 isoleucine, 28 leucine, 7 tyrosine, 7 phenylalanine, 5 histidine, 14 lysine, 16 arginine, 2 tryptophan, no --SS-- bonds or free --SH. Guanosine(5')pentaphospho(5')adenosine is a very strong inhibitor similar to adenosine(5')pentaphospho(5')adenosine as an inhibitor of cytosolic adenylate kinase."}
{"id": "PMID:218813", "title": "Mitochondrial GTP-AMP phosphotransferase. 2. Kinetic and equilibrium dialysis studies.", "content": "Kinetic and equilibrium dialysis substrate binding studies have been done to investigate the properties of mitochondrial GTP-AMP phosphotransferase. The results show that the enzyme has a specific requirement for divalent metal ions, namely Mg2+, Mn2+ or Ca2+ (Ca2+ is active only in the forward direction, the direction of formation of ADP). The reaction rate depends upon the ratio [Mg2+]:[substrate] rather than on the metal ion concentration alone. The enzymatic activity is influenced by NaCl (or KCl) and optimum pH occurs at 11.5 and 9.5 for guanosine and inosine nucleotides respectively. Examination of binding of substrates to the enzyme showed that there is one binding site (GTP site) for MgGTP, GTP, MgGDP or GDP per molecule of enzyme, with dissociation constants of 4.5, 4.4, 3.0, 2.2 micron respectively and one binding site (AMP site) for AMP, ADP or ATP per molecule of enzyme with dissociation constants of 20.9, 33.4 and 33.4 microns respectively. Since, within the limitations of equilibrium dialysis used in the present studies, AMP binding to one site of the enzyme could be detected only when GDP or GTP is present, the mechanism of the forward reaction may be assumed to be nearly ordered. For the reverse reaction there is no requirement of order of binding of the two nucleotides and so the mechanism of reaction may be assumed to be random.", "contents": "Mitochondrial GTP-AMP phosphotransferase. 2. Kinetic and equilibrium dialysis studies. Kinetic and equilibrium dialysis substrate binding studies have been done to investigate the properties of mitochondrial GTP-AMP phosphotransferase. The results show that the enzyme has a specific requirement for divalent metal ions, namely Mg2+, Mn2+ or Ca2+ (Ca2+ is active only in the forward direction, the direction of formation of ADP). The reaction rate depends upon the ratio [Mg2+]:[substrate] rather than on the metal ion concentration alone. The enzymatic activity is influenced by NaCl (or KCl) and optimum pH occurs at 11.5 and 9.5 for guanosine and inosine nucleotides respectively. Examination of binding of substrates to the enzyme showed that there is one binding site (GTP site) for MgGTP, GTP, MgGDP or GDP per molecule of enzyme, with dissociation constants of 4.5, 4.4, 3.0, 2.2 micron respectively and one binding site (AMP site) for AMP, ADP or ATP per molecule of enzyme with dissociation constants of 20.9, 33.4 and 33.4 microns respectively. Since, within the limitations of equilibrium dialysis used in the present studies, AMP binding to one site of the enzyme could be detected only when GDP or GTP is present, the mechanism of the forward reaction may be assumed to be nearly ordered. For the reverse reaction there is no requirement of order of binding of the two nucleotides and so the mechanism of reaction may be assumed to be random."}
{"id": "PMID:218815", "title": "A DNA-unwinding enzyme induced in bacteriophage-T4-infected Escherichia coli cells.", "content": "A single-stranded DNA-dependent ATP gamma-phosphohydrolase of Mr 56000 induced after infection of Escherichia coli cells with bacteriophage T4, probably the ATPase dependent on gene dda of the phage, was isolated. Studies on the enzyme show that in the presence of ATP and M2+ ions it is capable of dissociating partially double-stranded fd bacteriophage DNA into the single strands and that some 3000 enzyme copies are required to unwind the 6400-nucleotides-long DNA. Unwinding is inhibited by reducing the length of the single-stranded portion of DNA to two nucleotides. In addition it can be inhibited by sulfhydryl reagents which block the ATPase or by trapping free enzyme molecules in the assay system. The results suggest that unwinding is initiated near the single-stranded portion of the DNA and is driven by the ATPase. It further appears that the enzyme unwinds by adsorbing to the DNA. Affinity of the enzyme for double-standed DNA is not detectable by DNA binding assay.", "contents": "A DNA-unwinding enzyme induced in bacteriophage-T4-infected Escherichia coli cells. A single-stranded DNA-dependent ATP gamma-phosphohydrolase of Mr 56000 induced after infection of Escherichia coli cells with bacteriophage T4, probably the ATPase dependent on gene dda of the phage, was isolated. Studies on the enzyme show that in the presence of ATP and M2+ ions it is capable of dissociating partially double-stranded fd bacteriophage DNA into the single strands and that some 3000 enzyme copies are required to unwind the 6400-nucleotides-long DNA. Unwinding is inhibited by reducing the length of the single-stranded portion of DNA to two nucleotides. In addition it can be inhibited by sulfhydryl reagents which block the ATPase or by trapping free enzyme molecules in the assay system. The results suggest that unwinding is initiated near the single-stranded portion of the DNA and is driven by the ATPase. It further appears that the enzyme unwinds by adsorbing to the DNA. Affinity of the enzyme for double-standed DNA is not detectable by DNA binding assay."}
{"id": "PMID:218816", "title": "Diglyceride kinase from Escherichia coli. Purification in organic solvent and some properties of the enzyme.", "content": "The diglyceride kinase activity of membranes from Escherichia coli was extracted into acidic butan-1-ol. The enzyme was purified in organic solvent by precipitation at -20 degrees C, chromatography on DEAE-cellulose and repeated chromatography on Sephadex LH-60. The final 1460-fold purified enzyme preparation gave a single protein band upon isoelectric focusing in the presence of Triton X-100 (pI, 4.0) and upon polyacrylamide-gel electrophoresis in the presence of sodium dodecylsulphate. The latter method as well as gel chromatography on Sephadex LH-60 indicated a molecular weight of about 15400. The purified enzyme was devoid of lipid, and it required re-addition of lipid for activity. sn-1,2-Dipalmitate and ceramide were phosphorylated, whereas the C55-isoprenoid alcohol, ficaprenol, did not serve as a substrate under the same conditions. Conversely, the butanol-soluble C55-isoprenoid-alcohol kinase from Staphylococcus aureus did not phosphorylate sn-1,2-dipalmitate.", "contents": "Diglyceride kinase from Escherichia coli. Purification in organic solvent and some properties of the enzyme. The diglyceride kinase activity of membranes from Escherichia coli was extracted into acidic butan-1-ol. The enzyme was purified in organic solvent by precipitation at -20 degrees C, chromatography on DEAE-cellulose and repeated chromatography on Sephadex LH-60. The final 1460-fold purified enzyme preparation gave a single protein band upon isoelectric focusing in the presence of Triton X-100 (pI, 4.0) and upon polyacrylamide-gel electrophoresis in the presence of sodium dodecylsulphate. The latter method as well as gel chromatography on Sephadex LH-60 indicated a molecular weight of about 15400. The purified enzyme was devoid of lipid, and it required re-addition of lipid for activity. sn-1,2-Dipalmitate and ceramide were phosphorylated, whereas the C55-isoprenoid alcohol, ficaprenol, did not serve as a substrate under the same conditions. Conversely, the butanol-soluble C55-isoprenoid-alcohol kinase from Staphylococcus aureus did not phosphorylate sn-1,2-dipalmitate."}
{"id": "PMID:218817", "title": "Replication of M13 duplex DNA in soluble extracts of Escherichia coli. Effect of helix-destabilising proteins.", "content": "Soluble extracts of M13-am5-infected Escherichia coli cells can carry out multiple rounds of M13 duplex DNA replication when supplemented with helix-destabilising protein of E. coli. Similarly addition of the helix-destabilising M13 gene 5 protein in low concentrations (up to 30 micrograms/ml) stimulates the replication of double-stranded M13 DNA. In contrast, higher concentrations of gene 5 protein (but not of E. coli helix-destabilising protein) cause a preferential inhibition of complementary strand synthesis resulting in a switch from double-strand replication to single-strand synthesis. Depending on the addition of the appropriate amounts of these two helix-destabilising proteins either stage of M13 DNA replication can now be studied with cell-free preparations.", "contents": "Replication of M13 duplex DNA in soluble extracts of Escherichia coli. Effect of helix-destabilising proteins. Soluble extracts of M13-am5-infected Escherichia coli cells can carry out multiple rounds of M13 duplex DNA replication when supplemented with helix-destabilising protein of E. coli. Similarly addition of the helix-destabilising M13 gene 5 protein in low concentrations (up to 30 micrograms/ml) stimulates the replication of double-stranded M13 DNA. In contrast, higher concentrations of gene 5 protein (but not of E. coli helix-destabilising protein) cause a preferential inhibition of complementary strand synthesis resulting in a switch from double-strand replication to single-strand synthesis. Depending on the addition of the appropriate amounts of these two helix-destabilising proteins either stage of M13 DNA replication can now be studied with cell-free preparations."}
{"id": "PMID:218818", "title": "Spin transition of camphor-bound cytochrome P-450. 1. local paH and electrostatic interactions.", "content": "Variations of the spin state in camphor-bound cytochrome P-450 are interpreted in the light of the polyelectrolyte theory and its implications on the microenvironment of the heme. The ratio of high-spin to low-spin iron can serve as a tool to determine the local paH in the microenvironment of a group (pK0, app approximately 5.4) which governs the spin state. The local paH depends on the electrostatic potential created by negatively charged groups (pKa = 5.6), modulated in turn by paH and by the screening effect of ionic strength. A model is given for the proton-coupled spin state change.", "contents": "Spin transition of camphor-bound cytochrome P-450. 1. local paH and electrostatic interactions. Variations of the spin state in camphor-bound cytochrome P-450 are interpreted in the light of the polyelectrolyte theory and its implications on the microenvironment of the heme. The ratio of high-spin to low-spin iron can serve as a tool to determine the local paH in the microenvironment of a group (pK0, app approximately 5.4) which governs the spin state. The local paH depends on the electrostatic potential created by negatively charged groups (pKa = 5.6), modulated in turn by paH and by the screening effect of ionic strength. A model is given for the proton-coupled spin state change."}
{"id": "PMID:218821", "title": "Effect of triamcinolone on renal and hepatic phosphoenolpyruvate carboxykinase in the newborn rat. Changes in the rate of synthesis of the enzyme and in the activity of its translatable messenger RNA.", "content": "The effects of triamcinolone on renal and hepatic phosphoenolpyruvate carboxykinase activity in the developing rat were investigated. The hormone induced increases in pre-existing enzyme activity of both tissues in fetal and neonatal rats, yet did not cause the primary appearance of phosphoenolpyruvate carboxykinase activity in utero. Neonatal hepatic phosphoenolpyruvate carboxykinase activity was increased 2--3 fold by triamcinolone form the 3rd to the 15th postnatal day. This was shown to be additive to the effect of Bt2cAMP on enzyme activity. The increases in phosphoenolpyruvate carboxykinase activity were demonstrated to be due to increased synthesis of the enzyme, which was accompanied by a proportionate increase in the amount of functional phosphoenolpyruvate carboxykinase mRNA, as measured by the polyribosomal and poly(A)-containing RNA directed cell-free synthesis of the enzyme. The demonstration of a triamcinolone effect on kidney and liver phosphoenolpyruvate carboxykinase activity in fetal and neonatal rats provides support for a possible role of glucocorticoids in the regulation of phosphoenolpyruvate carboxykinase activity during development.", "contents": "Effect of triamcinolone on renal and hepatic phosphoenolpyruvate carboxykinase in the newborn rat. Changes in the rate of synthesis of the enzyme and in the activity of its translatable messenger RNA. The effects of triamcinolone on renal and hepatic phosphoenolpyruvate carboxykinase activity in the developing rat were investigated. The hormone induced increases in pre-existing enzyme activity of both tissues in fetal and neonatal rats, yet did not cause the primary appearance of phosphoenolpyruvate carboxykinase activity in utero. Neonatal hepatic phosphoenolpyruvate carboxykinase activity was increased 2--3 fold by triamcinolone form the 3rd to the 15th postnatal day. This was shown to be additive to the effect of Bt2cAMP on enzyme activity. The increases in phosphoenolpyruvate carboxykinase activity were demonstrated to be due to increased synthesis of the enzyme, which was accompanied by a proportionate increase in the amount of functional phosphoenolpyruvate carboxykinase mRNA, as measured by the polyribosomal and poly(A)-containing RNA directed cell-free synthesis of the enzyme. The demonstration of a triamcinolone effect on kidney and liver phosphoenolpyruvate carboxykinase activity in fetal and neonatal rats provides support for a possible role of glucocorticoids in the regulation of phosphoenolpyruvate carboxykinase activity during development."}
{"id": "PMID:218822", "title": "Congenital mesoblastic nephroma.", "content": "A case of mesoblastic nephroma in an infant with a 3-year, disease-free, postoperative survival period is reported. The histological aspects, with emphasis on differential diagnosis from Wilm's tumour are described.", "contents": "Congenital mesoblastic nephroma. A case of mesoblastic nephroma in an infant with a 3-year, disease-free, postoperative survival period is reported. The histological aspects, with emphasis on differential diagnosis from Wilm's tumour are described."}
{"id": "PMID:218823", "title": "(7-Ile) angiotensin III: a relatively selective antagonist of angiotensin steroidogenesis.", "content": "The effects of (7Ile) angiotensin III (AIII) and (1-Sar-8-Ile) angiotensin II (AII) on the pressor and steroidogenic effects of angiotensin were compared in conscious rats. (1-Sar-8-Ile) AII (500 ng/kg/min) equally inhibited the pressor responses of AII, AIII and (des-1-Asp) AI by 99% (P less than 0.0001) while (7-Ile) AIII (500 ng/kg/min) was without effect. The steroidogenic effects of AII, AIII and (des-1-Asp) AI (300 ng/kg/min) were inhibited by (1-Sar-8-Ile) AII by 83%, 69% and 50%, respectively, whereas (7-Ile) AIII inhibited their steroidogenic effects by 35%, 62% and 25%. respectively. In contrast, ACTH or potassium stimulated aldosterone release was not altered by either antagonist. In sodium depleted rats, (7-Ile) AII reduced the elevated serum aldosterone levels by 64% without altering the blood pressure, while (1-Sar-8-Ile) AII lowered the blood pressure without altering the concentration of aldosterone present in the serum. Thus, (7-Ile) AIII is relatively selective in its ability to antagonize the adrenal actions of endogenous and exogenous angiontensins when compared to the pressor actions of these peptides. Furthermore, these angiotensin antagonists appear to be useful as pharmacologic tools in assessing the characteristics of the angiotensin receptors in a particular tissue.", "contents": "(7-Ile) angiotensin III: a relatively selective antagonist of angiotensin steroidogenesis. The effects of (7Ile) angiotensin III (AIII) and (1-Sar-8-Ile) angiotensin II (AII) on the pressor and steroidogenic effects of angiotensin were compared in conscious rats. (1-Sar-8-Ile) AII (500 ng/kg/min) equally inhibited the pressor responses of AII, AIII and (des-1-Asp) AI by 99% (P less than 0.0001) while (7-Ile) AIII (500 ng/kg/min) was without effect. The steroidogenic effects of AII, AIII and (des-1-Asp) AI (300 ng/kg/min) were inhibited by (1-Sar-8-Ile) AII by 83%, 69% and 50%, respectively, whereas (7-Ile) AIII inhibited their steroidogenic effects by 35%, 62% and 25%. respectively. In contrast, ACTH or potassium stimulated aldosterone release was not altered by either antagonist. In sodium depleted rats, (7-Ile) AII reduced the elevated serum aldosterone levels by 64% without altering the blood pressure, while (1-Sar-8-Ile) AII lowered the blood pressure without altering the concentration of aldosterone present in the serum. Thus, (7-Ile) AIII is relatively selective in its ability to antagonize the adrenal actions of endogenous and exogenous angiontensins when compared to the pressor actions of these peptides. Furthermore, these angiotensin antagonists appear to be useful as pharmacologic tools in assessing the characteristics of the angiotensin receptors in a particular tissue."}
{"id": "PMID:218824", "title": "The effects of kininase II inhibition by SQ 14225 on kidney kallikrein-kinin and prostaglandin systems in conscious dogs.", "content": "The novel kininase II inhibitor SQ 14225 was intravenously administered to normal conscious dogs at the dose of 0.1 mg/kg. Urine kinin excretion increased from 14 +/- 6 ng/h to 163 +/- 18 ng/h. Separation by column chromatography showed that the increased urine kinin excretion was due to increased excretion of bradykinin. The enhanced urinary kinin excretion was associated by increased sodium (70%) and decreased kallikrein (27%) excretion. Urine volume and urinary prostaglandin excretion were not significantly affected by SQ 14225 treatment.", "contents": "The effects of kininase II inhibition by SQ 14225 on kidney kallikrein-kinin and prostaglandin systems in conscious dogs. The novel kininase II inhibitor SQ 14225 was intravenously administered to normal conscious dogs at the dose of 0.1 mg/kg. Urine kinin excretion increased from 14 +/- 6 ng/h to 163 +/- 18 ng/h. Separation by column chromatography showed that the increased urine kinin excretion was due to increased excretion of bradykinin. The enhanced urinary kinin excretion was associated by increased sodium (70%) and decreased kallikrein (27%) excretion. Urine volume and urinary prostaglandin excretion were not significantly affected by SQ 14225 treatment."}
{"id": "PMID:218825", "title": "Effects of calcium on a cyclic nucleotide system in soleus motor nerve terminals.", "content": "The effects of increased extracellular calcium levels on the responses of the motor nerve terminal to agents that increased intracellular levels of cyclic AMP was studied on the in vivo cat soleus muscle preparation. The neural and muscle responses to intra-arterially administered NaF, an activator of adenylate cyclase, and dbcAMP progressively increased as blood calcium levels rose. These results provide additional support for the hypothesis of an interaction between calcium and cyclic AMP in motor nerve endings.", "contents": "Effects of calcium on a cyclic nucleotide system in soleus motor nerve terminals. The effects of increased extracellular calcium levels on the responses of the motor nerve terminal to agents that increased intracellular levels of cyclic AMP was studied on the in vivo cat soleus muscle preparation. The neural and muscle responses to intra-arterially administered NaF, an activator of adenylate cyclase, and dbcAMP progressively increased as blood calcium levels rose. These results provide additional support for the hypothesis of an interaction between calcium and cyclic AMP in motor nerve endings."}
{"id": "PMID:218826", "title": "Maturation process of secondary ossification centers in the rat and assessment of bone age.", "content": "The maturation process from the appearance to the fusion of the secondary ossification centers of extremities was studied in Wistar rats aged 0 to 134 weeks. The examination of the secondary ossification centers made by radiography. The assessment of the stage of development was made in accordance with the criteria proposed by Ohwada and Sutow. The secondary ossification center was found to be take one of the following three types of maturation processes : (1) the acute ossification, (2) the delayed ossification, and (3) the incomplete ossification. No fusion was observed up to 134 weeks in certain epiphyses of the rat. This type of ossification designated as the incomplete ossification may be specific to the mouse and rat. The relative lengths of time required for appearance and fusion in the average prospective life were obtained for the rat. They were compared with those of the mouse and man. The relative length of time necessary for maturity of the secondary ossification centers was shown to be the shortest in the rat and the longest in man. The results suggested that the rat may reach maturity in the bone age at 17 to 21 weeks of age. The rat at this age may be regarded as being adult corresponding to age 17 weeks in mice and 18 to 24 years in man.", "contents": "Maturation process of secondary ossification centers in the rat and assessment of bone age. The maturation process from the appearance to the fusion of the secondary ossification centers of extremities was studied in Wistar rats aged 0 to 134 weeks. The examination of the secondary ossification centers made by radiography. The assessment of the stage of development was made in accordance with the criteria proposed by Ohwada and Sutow. The secondary ossification center was found to be take one of the following three types of maturation processes : (1) the acute ossification, (2) the delayed ossification, and (3) the incomplete ossification. No fusion was observed up to 134 weeks in certain epiphyses of the rat. This type of ossification designated as the incomplete ossification may be specific to the mouse and rat. The relative lengths of time required for appearance and fusion in the average prospective life were obtained for the rat. They were compared with those of the mouse and man. The relative length of time necessary for maturity of the secondary ossification centers was shown to be the shortest in the rat and the longest in man. The results suggested that the rat may reach maturity in the bone age at 17 to 21 weeks of age. The rat at this age may be regarded as being adult corresponding to age 17 weeks in mice and 18 to 24 years in man."}
{"id": "PMID:218829", "title": "Examination of latent infection in germfree mice for some murine viruses.", "content": "Sera from some groups of germfree mice were examined for reactivity against Sendai, reo 3, Theiler's GD VII, ectromelia, and mouse hepatitis virus antigens. Of 51 sera collected in September and October 1976 and in August and September 1977 from one germfree mouse breeding colony, there was no positive reaction against all the antigens tested. Moreover, the attempt of virus isolation from homogenates of various organs including lungs, liver, kidneys, and intestines of 6 germfree mice was unsuccessful.", "contents": "Examination of latent infection in germfree mice for some murine viruses. Sera from some groups of germfree mice were examined for reactivity against Sendai, reo 3, Theiler's GD VII, ectromelia, and mouse hepatitis virus antigens. Of 51 sera collected in September and October 1976 and in August and September 1977 from one germfree mouse breeding colony, there was no positive reaction against all the antigens tested. Moreover, the attempt of virus isolation from homogenates of various organs including lungs, liver, kidneys, and intestines of 6 germfree mice was unsuccessful."}
{"id": "PMID:218833", "title": "Serum lipoprotein inhibitors of granulopoiesis in human bone marrow cultures.", "content": "Ammonium sulphate fractionation of human serum showed that two fractions contained an inhibitor of cluster and colony formation in agar cultures of human bone marrow cells. Further investigations demonstrated this inhibition to be caused by lipoproteins. When freshly prepared, only light density lipoproteins (LDL) were found to be inhibitory. During storage, very light density lipoproteins (VLDL) acquired inhibitory activity, while high density lipoproteins (HDL) did not show any inhibition of human bone marrow cultures. The possibility of toxic degradation of lipoproteins as an explanation for the inhibition was investigated by preincubation of human marrow cells with lipoproteins for 6 hours (37 degrees C) after storage of the lipoproteins under nitrogen (4 degrees C) for various intervals up to 48 days. Preincubation was found to be non-toxic (viable cell counts) and without colony/cluster-reducing ability for incubated marrow cells compared to controls. Addition of lipoproteins to mouse marrow cells and Ehrlich ascites tumour cells resulted in no change in colony formation by Ehrlich cells, whereas mouse marrow cells were inhibited, but to a lesser degree than human marrow cells.", "contents": "Serum lipoprotein inhibitors of granulopoiesis in human bone marrow cultures. Ammonium sulphate fractionation of human serum showed that two fractions contained an inhibitor of cluster and colony formation in agar cultures of human bone marrow cells. Further investigations demonstrated this inhibition to be caused by lipoproteins. When freshly prepared, only light density lipoproteins (LDL) were found to be inhibitory. During storage, very light density lipoproteins (VLDL) acquired inhibitory activity, while high density lipoproteins (HDL) did not show any inhibition of human bone marrow cultures. The possibility of toxic degradation of lipoproteins as an explanation for the inhibition was investigated by preincubation of human marrow cells with lipoproteins for 6 hours (37 degrees C) after storage of the lipoproteins under nitrogen (4 degrees C) for various intervals up to 48 days. Preincubation was found to be non-toxic (viable cell counts) and without colony/cluster-reducing ability for incubated marrow cells compared to controls. Addition of lipoproteins to mouse marrow cells and Ehrlich ascites tumour cells resulted in no change in colony formation by Ehrlich cells, whereas mouse marrow cells were inhibited, but to a lesser degree than human marrow cells."}
{"id": "PMID:218848", "title": "Hormone receptor changes during adulthood and senescence: significance for aging research.", "content": "Receptors for various hormones have been examined throughout the adult life span. In most of these studies receptor concentrations were found to decrease with increasing age, either during senescence or earlier in adulthood. In contrast, binding affinities did not change with age. Tissues and cells examined have included liver, brain, adipose tissue, skeletal muscle, prostate, fibroblasts, and lymphocytes. Receptors for steroids as well as membrane-active hormones such as insulin, glucagon, catecholamines, and prolactin were studied. Rats, mice, dogs, and humans have been employed. Changes in hormone receptor levels appear to constitute a common manifestation of the aging process, and offer interesting model systems in which to study the control of genetic expression during senescence.", "contents": "Hormone receptor changes during adulthood and senescence: significance for aging research. Receptors for various hormones have been examined throughout the adult life span. In most of these studies receptor concentrations were found to decrease with increasing age, either during senescence or earlier in adulthood. In contrast, binding affinities did not change with age. Tissues and cells examined have included liver, brain, adipose tissue, skeletal muscle, prostate, fibroblasts, and lymphocytes. Receptors for steroids as well as membrane-active hormones such as insulin, glucagon, catecholamines, and prolactin were studied. Rats, mice, dogs, and humans have been employed. Changes in hormone receptor levels appear to constitute a common manifestation of the aging process, and offer interesting model systems in which to study the control of genetic expression during senescence."}
{"id": "PMID:218849", "title": "Age-related alterations in the development of adrenergic denervation supersensitivity.", "content": "The density of beta-adrenergic receptors in the central nervous system exhibits marked age-related changes. In general, there is an initial increase in receptors soon after birth followed by a decline with advancing age; the specific pattern of the development and loss of receptors is dependent upon the brain area. The ontogenetic increase in the density of adrenergic receptors coincides temporally with the development of responsiveness to catecholamines but can proceed without an adrenergic innervation. This suggests that the biosynthesis of receptors is genetically predetermined and does not require an adrenergic input for initiation. Decreasing adrenergic activity produces an increased number of beta-receptors and a supersensitive response to adrenergic agonists. The decline in beta-receptors with advanced age appears to be related to this phenomenon of denervation supersensitivity since certain aged tissues have a diminished capacity to develop an increased number of receptors in response to a reduced sympathetic input. We conclude that the decline in beta-adrenergic receptors with age may explain the age-related decrease in the sensitivity of adenylate cyclase to catecholamines, and, consequently, the reduced physiological response to adrenergic stimuli. The mechanism for this loss of receptors may be the inability of aged tissue to develop a supersensitivity response in reaction to diminished sympathetic activity.", "contents": "Age-related alterations in the development of adrenergic denervation supersensitivity. The density of beta-adrenergic receptors in the central nervous system exhibits marked age-related changes. In general, there is an initial increase in receptors soon after birth followed by a decline with advancing age; the specific pattern of the development and loss of receptors is dependent upon the brain area. The ontogenetic increase in the density of adrenergic receptors coincides temporally with the development of responsiveness to catecholamines but can proceed without an adrenergic innervation. This suggests that the biosynthesis of receptors is genetically predetermined and does not require an adrenergic input for initiation. Decreasing adrenergic activity produces an increased number of beta-receptors and a supersensitive response to adrenergic agonists. The decline in beta-receptors with advanced age appears to be related to this phenomenon of denervation supersensitivity since certain aged tissues have a diminished capacity to develop an increased number of receptors in response to a reduced sympathetic input. We conclude that the decline in beta-adrenergic receptors with age may explain the age-related decrease in the sensitivity of adenylate cyclase to catecholamines, and, consequently, the reduced physiological response to adrenergic stimuli. The mechanism for this loss of receptors may be the inability of aged tissue to develop a supersensitivity response in reaction to diminished sympathetic activity."}
{"id": "PMID:218850", "title": "Aging and monoamine receptors in brain.", "content": "Biochemical evidence is presented for selective decreases in biogenic amine receptor systems with age in the rabbit. Dopamine-stimulated adenylate cyclase activity in striatum, hypothalamus, frontal cortex, and anterior limbic cortex declined by about 50% as rabbits aged from less than 1 to 5 years of age. Similar decreases were found for histamine-stimulated activity in hypothalamus and the cortical regions. These changes were in maximal response rather than in affinity for amine. In contrast, dopamine-stimulated adenylate cyclase of retina and both basal and Gpp(NH)p-stimulated activity in these regions were not altered with age. In addition, with age the number of binding sites for [3H]spiroperidol, a dopamine antagonist, decreased by 30--40% without change in ligand affinity in striatum and limbic cortex. These changes in striatum and  cortex occurred in the absence of decreases in either dopamine concentration or choline acetylase activity. It is proposed that selective age-dependent decreases in the functional number of biogenic amine receptors occur in the absence of, or independent from neuronal cell loss, possibly by a mechanism of desensitization. These changes occurred in brain regions that in man are thought to be of importance in the age-related loss of cerebral function.", "contents": "Aging and monoamine receptors in brain. Biochemical evidence is presented for selective decreases in biogenic amine receptor systems with age in the rabbit. Dopamine-stimulated adenylate cyclase activity in striatum, hypothalamus, frontal cortex, and anterior limbic cortex declined by about 50% as rabbits aged from less than 1 to 5 years of age. Similar decreases were found for histamine-stimulated activity in hypothalamus and the cortical regions. These changes were in maximal response rather than in affinity for amine. In contrast, dopamine-stimulated adenylate cyclase of retina and both basal and Gpp(NH)p-stimulated activity in these regions were not altered with age. In addition, with age the number of binding sites for [3H]spiroperidol, a dopamine antagonist, decreased by 30--40% without change in ligand affinity in striatum and limbic cortex. These changes in striatum and  cortex occurred in the absence of decreases in either dopamine concentration or choline acetylase activity. It is proposed that selective age-dependent decreases in the functional number of biogenic amine receptors occur in the absence of, or independent from neuronal cell loss, possibly by a mechanism of desensitization. These changes occurred in brain regions that in man are thought to be of importance in the age-related loss of cerebral function."}
{"id": "PMID:218855", "title": "Lipoprotein secretion by rat liver Golgi apparatus. Lipoprotein particles and lipase activity.", "content": "Lipoprotein particles of the size range of very low density lipoproteins in smooth endoplasmic reticulum, peripheral elements of the Golgi apparatus, and secretory vesicles of the immature Golgi apparatus face are 55 to 80 nm in diameter. Particles in mature secretory vesicles are smaller (45 nm). Concomitant with the change in particle size, the lumina of mature vesicles increase in electron density. A technique to fractionate immature and mature secretory vesicles was based on precipitation of a cupric-ferrocyanide complex (Hatchett's brown) through the action of a NADH-ferricyanide oxido-reductase resistant to glutaraldehyde which is characteristic of the membranes of mature secretory vesicles and of the plasma membrane of liver. Mature secretory vesicle fractions so isolated were enriched in cholesterol and depleted in triglycerides relative to immature vesicles on a phospholipid basis. Lipase activity was present in secretory vesicle fractions of the Golgi apparatus as shown by biochemical analysis and by cytochemistry. Cytochemical studies showed lipase to be present in both mature and immature vesicles but most evident in immature vesicles. The findings suggest that some very low density lipoprotein particles are converted to particles of smaller diameter during transit through Golgi apparatus. A lipase-mediated hydrolysis of triglycerides may relate to the transformation.", "contents": "Lipoprotein secretion by rat liver Golgi apparatus. Lipoprotein particles and lipase activity. Lipoprotein particles of the size range of very low density lipoproteins in smooth endoplasmic reticulum, peripheral elements of the Golgi apparatus, and secretory vesicles of the immature Golgi apparatus face are 55 to 80 nm in diameter. Particles in mature secretory vesicles are smaller (45 nm). Concomitant with the change in particle size, the lumina of mature vesicles increase in electron density. A technique to fractionate immature and mature secretory vesicles was based on precipitation of a cupric-ferrocyanide complex (Hatchett's brown) through the action of a NADH-ferricyanide oxido-reductase resistant to glutaraldehyde which is characteristic of the membranes of mature secretory vesicles and of the plasma membrane of liver. Mature secretory vesicle fractions so isolated were enriched in cholesterol and depleted in triglycerides relative to immature vesicles on a phospholipid basis. Lipase activity was present in secretory vesicle fractions of the Golgi apparatus as shown by biochemical analysis and by cytochemistry. Cytochemical studies showed lipase to be present in both mature and immature vesicles but most evident in immature vesicles. The findings suggest that some very low density lipoprotein particles are converted to particles of smaller diameter during transit through Golgi apparatus. A lipase-mediated hydrolysis of triglycerides may relate to the transformation."}
{"id": "PMID:218856", "title": "Dependence of intracellular alkali-ion concentrations of 3T3 and SV 40-3T3 cells on growth density.", "content": "Intracellular contents of potassium and of sodium are determined for 3T3 and SV 40-3T3 cells in dependence of growth density. In parallel, total cell volume and volume of intracellular water is determined for these cells suspended in physiological buffer. Intracellular potassium concentration thus evaluated for suspended 3T3 cells exhibits a sharp decrease at cellular growth densities which lead to density dependent inhibition of cell proliferation. In the case of SV 40-3T3 cells, this drop of potassium concentration with increasing cellular growth density is not observed, which correlates well with the absence of cell density dependent inhibition of cell growth in the transformed cell line. These results support the notion that processes of stimulation of quiescent 3T3 cells or of cell density dependent inhibition of their proliferation are mediated by processes including changes of potassium transport characteristics leading to increase or decrease respectively of their intracellular potassium concentration. Furthermore, these and other results suggest, that a difference between normal and transformed cells most relevant to their different proliferation behaviour might reside in different transport characteristics for potassium of the plasma membranes of these cells.", "contents": "Dependence of intracellular alkali-ion concentrations of 3T3 and SV 40-3T3 cells on growth density. Intracellular contents of potassium and of sodium are determined for 3T3 and SV 40-3T3 cells in dependence of growth density. In parallel, total cell volume and volume of intracellular water is determined for these cells suspended in physiological buffer. Intracellular potassium concentration thus evaluated for suspended 3T3 cells exhibits a sharp decrease at cellular growth densities which lead to density dependent inhibition of cell proliferation. In the case of SV 40-3T3 cells, this drop of potassium concentration with increasing cellular growth density is not observed, which correlates well with the absence of cell density dependent inhibition of cell growth in the transformed cell line. These results support the notion that processes of stimulation of quiescent 3T3 cells or of cell density dependent inhibition of their proliferation are mediated by processes including changes of potassium transport characteristics leading to increase or decrease respectively of their intracellular potassium concentration. Furthermore, these and other results suggest, that a difference between normal and transformed cells most relevant to their different proliferation behaviour might reside in different transport characteristics for potassium of the plasma membranes of these cells."}
{"id": "PMID:218863", "title": "Hepatocellular transplantation --morphological study on hepatocytes transplanted into rat spleen--.", "content": "Hepatocellular transplantation into the spleen was investigated as a new attempt in utilizing isolated hepatocytes to compensate for impaired liver function. Present study was undertaken to evaluate morphological and histochemical alterations up to 6 weeks following transplantation in hepatocytes transplanted into the splenic parenchyma. Light microscopic studies revealed viable hepatocellular islets in the splenic parenchyma up to 6 weeks, although minimal cytoplasmic changes were observed. Electron microscopic studies demonstrated moderate changes in organelles, which developed gradually as the time after transplantation proceeded. Distortion and fragmentation of the membranes around the cytoplasm and organelles were not recognized. Moreover, newly formed bile canaliculi and tight junctions which indicate reconstruction of hepatic plates were observed between adjacent cell membranes, and enzyme activities were detected by cytochemical determination of glucose-6-phosphatase in the hepatocytes even 6 weeks after transplantation. The transplanted hepatocytes preserved their characteristic enzyme and fine structures as hepatocytes up to 6 weeks. Our present study based on the persistence of cellular viability suggests that inoculated hepatocytes do maintain their hepatocellular functions after transplantation.", "contents": "Hepatocellular transplantation --morphological study on hepatocytes transplanted into rat spleen--. Hepatocellular transplantation into the spleen was investigated as a new attempt in utilizing isolated hepatocytes to compensate for impaired liver function. Present study was undertaken to evaluate morphological and histochemical alterations up to 6 weeks following transplantation in hepatocytes transplanted into the splenic parenchyma. Light microscopic studies revealed viable hepatocellular islets in the splenic parenchyma up to 6 weeks, although minimal cytoplasmic changes were observed. Electron microscopic studies demonstrated moderate changes in organelles, which developed gradually as the time after transplantation proceeded. Distortion and fragmentation of the membranes around the cytoplasm and organelles were not recognized. Moreover, newly formed bile canaliculi and tight junctions which indicate reconstruction of hepatic plates were observed between adjacent cell membranes, and enzyme activities were detected by cytochemical determination of glucose-6-phosphatase in the hepatocytes even 6 weeks after transplantation. The transplanted hepatocytes preserved their characteristic enzyme and fine structures as hepatocytes up to 6 weeks. Our present study based on the persistence of cellular viability suggests that inoculated hepatocytes do maintain their hepatocellular functions after transplantation."}
{"id": "PMID:218864", "title": "Small intestinal morphology and epithelial cell kinetics in lamb rotavirus infections.", "content": "Morphologic changes in the small intestine of rotavirus-infected gnotobiotic lambs were investigated by measurement of villi and crypts in histologic sections of jejunum, midgut, and posterior ileum. In midgut, villus atrophy developed within 12 hr of infection and was apparent until 72 hr after infection. Crypt hypertrophy was evident from 42 hr after infection until the end of the observation period (6 days after infection). Changes in posterior ileum were similar in extent, but jejunal changes were much less marked. The relatively mild effect in the jejunum is in accord with reports from other species, and provides a basis for questioning the assumption that human rotavirus affects mainly the foregut. Studies of epithelial cell kinetics were made on midgut using a microdissection and metaphase accumulation technique on sequential samples from anesthetized lambs. An increase in the cell production rate per crypt per hour from the overall control level of 5.8 was detected by 48 hr after infection. The maximum level of 21.2 was reached 8 days after infection, and this had returned to near normal by 15 days after infection. This large and sustained increase in crypt cell production probably underlies other previously described functional abnormalities.", "contents": "Small intestinal morphology and epithelial cell kinetics in lamb rotavirus infections. Morphologic changes in the small intestine of rotavirus-infected gnotobiotic lambs were investigated by measurement of villi and crypts in histologic sections of jejunum, midgut, and posterior ileum. In midgut, villus atrophy developed within 12 hr of infection and was apparent until 72 hr after infection. Crypt hypertrophy was evident from 42 hr after infection until the end of the observation period (6 days after infection). Changes in posterior ileum were similar in extent, but jejunal changes were much less marked. The relatively mild effect in the jejunum is in accord with reports from other species, and provides a basis for questioning the assumption that human rotavirus affects mainly the foregut. Studies of epithelial cell kinetics were made on midgut using a microdissection and metaphase accumulation technique on sequential samples from anesthetized lambs. An increase in the cell production rate per crypt per hour from the overall control level of 5.8 was detected by 48 hr after infection. The maximum level of 21.2 was reached 8 days after infection, and this had returned to near normal by 15 days after infection. This large and sustained increase in crypt cell production probably underlies other previously described functional abnormalities."}
{"id": "PMID:218866", "title": "Lethal herpes simplex virus type 1 hepatitis in a normal adult.", "content": "A fatal case of human herpes simplex type 1 hepatitis is presented and compared with cases previously reported. The patient presented with fulminant hepatic necrosis, coagulopathy, leukopenia, thrombocytopenia, and absence of typical herpetic mucocutaneous lesions. Liver biopsy helped to establish a presumptive diagnosis in this patient and in one previously reported case. Theoretically, early diagnosis might enable application of specific antiviral therapy in future cases of this usually fatal infection.", "contents": "Lethal herpes simplex virus type 1 hepatitis in a normal adult. A fatal case of human herpes simplex type 1 hepatitis is presented and compared with cases previously reported. The patient presented with fulminant hepatic necrosis, coagulopathy, leukopenia, thrombocytopenia, and absence of typical herpetic mucocutaneous lesions. Liver biopsy helped to establish a presumptive diagnosis in this patient and in one previously reported case. Theoretically, early diagnosis might enable application of specific antiviral therapy in future cases of this usually fatal infection."}
{"id": "PMID:218872", "title": "[Differential diagnosis of pigmented tumors].", "content": "Some frequent diagnostic problems and the most important clinical and histologic criteria in differential diagnosis of malignant melanomas, benign pigment cell nevi, melanotic epithelial neoplastic lesions and frequent haemosiderotic tumors are delineated in a condensed survey. Considering the variety of diagnostic errors, one should never treat respectively destroy pigmented tumors of the skin without histologic investigation.", "contents": "[Differential diagnosis of pigmented tumors]. Some frequent diagnostic problems and the most important clinical and histologic criteria in differential diagnosis of malignant melanomas, benign pigment cell nevi, melanotic epithelial neoplastic lesions and frequent haemosiderotic tumors are delineated in a condensed survey. Considering the variety of diagnostic errors, one should never treat respectively destroy pigmented tumors of the skin without histologic investigation."}
{"id": "PMID:218873", "title": "[Hormonal regulation and hormone therapy in childhood and adolescence. Part 1: development of endocrine glands, hormone production, menarche and secondary sex characteristics].", "content": "The growth curves of the endocrine glands in female puberty are described. Adrenarche with an elevated production of adrenal dehydroepiandrosterone marks the beginning of prepuberty. By decrease of hypothalamic sensitivity to sexual steroids begins the deviation of FSH and LH levels. Significant increases of gonadotrophins and prolactin occur during sleep. There is a good correlation between bone age, Tanner-stages of breast and pubic hair development and steroid hormone levels. Criteria of maturity for young girls including menarche and ovulation are given.", "contents": "[Hormonal regulation and hormone therapy in childhood and adolescence. Part 1: development of endocrine glands, hormone production, menarche and secondary sex characteristics]. The growth curves of the endocrine glands in female puberty are described. Adrenarche with an elevated production of adrenal dehydroepiandrosterone marks the beginning of prepuberty. By decrease of hypothalamic sensitivity to sexual steroids begins the deviation of FSH and LH levels. Significant increases of gonadotrophins and prolactin occur during sleep. There is a good correlation between bone age, Tanner-stages of breast and pubic hair development and steroid hormone levels. Criteria of maturity for young girls including menarche and ovulation are given."}
{"id": "PMID:218874", "title": "[Clinical and urological after care in gynecologic neoplasms].", "content": "Patients after operative and/or radiological therapy for cervical cancer should have gynecological follow-up examinations every two months in the first year. In cases of urological complications after irradiation therapy, radionephrography, infusion urogram, blood count, cystoscopy, and cystometry should also be carried out after two months. Depending on the clinical picture, radionephrography, blood count and urinalysis are to be repeated in regular intervals. After lymphography with positive findings, x-ray controls are necessary after two and four months. In cases of increasing hydronephrosis and hydroureter due to fibrostenosis of the ureter plastic surgery is recommended. Most urological complications are to be expected after radical operation and postoperative irradiation. In patients with endometrial uterine cancer, metastases mostly occur paraurethrally and in the lungs. Chest x-ray is to be taken every six months. Suspicious paraurethral hardening is cytologically diagnosed by needle biopsy. In ovarian carcinoma stage III and IV repeated x-ray controls of the lungs during longterm polychemotherapy are advisable. Prior to second look operations after combined treatment a second look laparoscopy is particularly important. Urological complications are more frequent after therapy of cervical cancer while ovarian carcinoma is more likely to develop complications of the small bowel.", "contents": "[Clinical and urological after care in gynecologic neoplasms]. Patients after operative and/or radiological therapy for cervical cancer should have gynecological follow-up examinations every two months in the first year. In cases of urological complications after irradiation therapy, radionephrography, infusion urogram, blood count, cystoscopy, and cystometry should also be carried out after two months. Depending on the clinical picture, radionephrography, blood count and urinalysis are to be repeated in regular intervals. After lymphography with positive findings, x-ray controls are necessary after two and four months. In cases of increasing hydronephrosis and hydroureter due to fibrostenosis of the ureter plastic surgery is recommended. Most urological complications are to be expected after radical operation and postoperative irradiation. In patients with endometrial uterine cancer, metastases mostly occur paraurethrally and in the lungs. Chest x-ray is to be taken every six months. Suspicious paraurethral hardening is cytologically diagnosed by needle biopsy. In ovarian carcinoma stage III and IV repeated x-ray controls of the lungs during longterm polychemotherapy are advisable. Prior to second look operations after combined treatment a second look laparoscopy is particularly important. Urological complications are more frequent after therapy of cervical cancer while ovarian carcinoma is more likely to develop complications of the small bowel."}
{"id": "PMID:218878", "title": "Multihormonal pituitary adenomas.", "content": "66 pituitary tumors detected at autopsy were investigated for the presence of corticotropin, beta-lipotrophin, growth hormone, prolactin, thyrotropin and gonadotropins by immunocytochemistry. 56 tumors contained hormone-producing cells; 45 were found to contain 2 or more hormones. This finding confirms and extends previous morphologic and clinical observations. The majority of pituitary tumors are mixed and they probably arise from impaired regulation at the hypothalamic and/or pituitary level.", "contents": "Multihormonal pituitary adenomas. 66 pituitary tumors detected at autopsy were investigated for the presence of corticotropin, beta-lipotrophin, growth hormone, prolactin, thyrotropin and gonadotropins by immunocytochemistry. 56 tumors contained hormone-producing cells; 45 were found to contain 2 or more hormones. This finding confirms and extends previous morphologic and clinical observations. The majority of pituitary tumors are mixed and they probably arise from impaired regulation at the hypothalamic and/or pituitary level."}
{"id": "PMID:218879", "title": "Preservation of the effects of pregnancy on rat islets of Langerhans in tissue culture.", "content": "Islets of Langerhans, isolated from normal or 19-day pregnant rats, were cultured for 20 h at 37 degrees C in tissue culture medium 199. When islets were cultured in medium containing low glucose (5.5 mM), the higher adenylate cyclase activity and insulin secretory responses characteristic of islets from pregnant rats were maintained during the test period of 29 h. Islets from normal and pregnant rats were also cultured for 20 h in medium containing a very high glucose concentration (83.3 mM) in order to load the B cells with glycogen. It was found, after glycogen loading, that, while adenylate cyclase activity increased to a greater extent in islets from pregnant rats than controls, this activity was not increased in proportion to the striking changes in insulin release rate observed in pregnant rat islets. The results show that the difference in insulin secretory response between islets from normal and pregnant rats may be preserved when the islets are cultured for 20 h, and that these differences are enhanced for a variety of reasons after culture of islets in 83.3 mM glucose.", "contents": "Preservation of the effects of pregnancy on rat islets of Langerhans in tissue culture. Islets of Langerhans, isolated from normal or 19-day pregnant rats, were cultured for 20 h at 37 degrees C in tissue culture medium 199. When islets were cultured in medium containing low glucose (5.5 mM), the higher adenylate cyclase activity and insulin secretory responses characteristic of islets from pregnant rats were maintained during the test period of 29 h. Islets from normal and pregnant rats were also cultured for 20 h in medium containing a very high glucose concentration (83.3 mM) in order to load the B cells with glycogen. It was found, after glycogen loading, that, while adenylate cyclase activity increased to a greater extent in islets from pregnant rats than controls, this activity was not increased in proportion to the striking changes in insulin release rate observed in pregnant rat islets. The results show that the difference in insulin secretory response between islets from normal and pregnant rats may be preserved when the islets are cultured for 20 h, and that these differences are enhanced for a variety of reasons after culture of islets in 83.3 mM glucose."}
{"id": "PMID:218880", "title": "Cytomegalovirus vaccine: a realistic appraisal.", "content": "The possible benefits and dangers of a vaccine program for CMV infection, especially congenital infection, cannot be rationally analyzed until more is known about the virus itself, including its manner of spread and the nature of host responses. Until then, trials with the experimental vaccines under development should be limited to patients at unusually high risk, such as those receiving renal transplants.", "contents": "Cytomegalovirus vaccine: a realistic appraisal. The possible benefits and dangers of a vaccine program for CMV infection, especially congenital infection, cannot be rationally analyzed until more is known about the virus itself, including its manner of spread and the nature of host responses. Until then, trials with the experimental vaccines under development should be limited to patients at unusually high risk, such as those receiving renal transplants."}
{"id": "PMID:218881", "title": "Neurofibrillary tangles induced by a sclerosing angioma.", "content": "A sclerosing angioma in the frontal cortex of a 40 year old woman produced local pressure, with resulting alteration of the blood-brain barrier. In the narrow cortical zone affected by chronic pressure, the level of aluminum was significantly elevated; and all neurons had neurofibrillary tangles of the Alzheimer type.", "contents": "Neurofibrillary tangles induced by a sclerosing angioma. A sclerosing angioma in the frontal cortex of a 40 year old woman produced local pressure, with resulting alteration of the blood-brain barrier. In the narrow cortical zone affected by chronic pressure, the level of aluminum was significantly elevated; and all neurons had neurofibrillary tangles of the Alzheimer type."}
{"id": "PMID:218882", "title": "Thorotrast induced hepatic cholangiocarcinoma and angiosarcoma.", "content": "A 49 year old woman developed hepatic cholangiocarcinoma and angiosarcoma 22 years after the administration of Thorotrast. The etiologic association between Thorotrast and a variety of malignant hepatic neoplasms is well known, but the simultaneous occurrence of two different hepatic neoplasms has not been previously reported.", "contents": "Thorotrast induced hepatic cholangiocarcinoma and angiosarcoma. A 49 year old woman developed hepatic cholangiocarcinoma and angiosarcoma 22 years after the administration of Thorotrast. The etiologic association between Thorotrast and a variety of malignant hepatic neoplasms is well known, but the simultaneous occurrence of two different hepatic neoplasms has not been previously reported."}
{"id": "PMID:218883", "title": "Malignant fibrous histiocytoma of bone: a study of 35 cases.", "content": "Thirty-five cases of primary malignant fibrous histiocytoma of bone are reported. Twenty of these cases were collected from a retrospective analysis of other malignant bone tumors. The age range was from 11 to 69 years; the average age was 34 years. The tumor occurred most commonly in the distal femur and proximal tibia. The distinguishing histologic feature was a storiform arrangement of spindle cells. The differential diagnosis included fibrosarcoma, osteogenic sarcoma, malignant giant cell tumor, malignant lymphoma, and metastatic carcinoma. Follow-up of at least three years was available in 21 cases. Of these, nine patients were alive and free of metastases three and one-half to 12 years after treatment. Two were alive with solitary metastases at three years, and 10 patients died between three months and three years after treatment. In four cases the lesions were multicentric at the time of diagnosis and in four cases were associated with bone infarction. This tumor must be recognized as an important complication of bone infarction and should be suspected when a patient with a known history of bone infarction develops a change in symptoms. Because the prognosis of this tumor is significantly better than that in those tumors with which it had been previously grouped, and in view of its association with bone infarction, it deserves to be maintained as a distinct clinicopathologic entity. Amputation is the treatment of choice.", "contents": "Malignant fibrous histiocytoma of bone: a study of 35 cases. Thirty-five cases of primary malignant fibrous histiocytoma of bone are reported. Twenty of these cases were collected from a retrospective analysis of other malignant bone tumors. The age range was from 11 to 69 years; the average age was 34 years. The tumor occurred most commonly in the distal femur and proximal tibia. The distinguishing histologic feature was a storiform arrangement of spindle cells. The differential diagnosis included fibrosarcoma, osteogenic sarcoma, malignant giant cell tumor, malignant lymphoma, and metastatic carcinoma. Follow-up of at least three years was available in 21 cases. Of these, nine patients were alive and free of metastases three and one-half to 12 years after treatment. Two were alive with solitary metastases at three years, and 10 patients died between three months and three years after treatment. In four cases the lesions were multicentric at the time of diagnosis and in four cases were associated with bone infarction. This tumor must be recognized as an important complication of bone infarction and should be suspected when a patient with a known history of bone infarction develops a change in symptoms. Because the prognosis of this tumor is significantly better than that in those tumors with which it had been previously grouped, and in view of its association with bone infarction, it deserves to be maintained as a distinct clinicopathologic entity. Amputation is the treatment of choice."}
{"id": "PMID:218889", "title": "Enzymatic methyl esterification of pituitary polypeptides.", "content": "Methyl esterification of pituitary polypeptides by protein methylase II (S-adenosylmethionine:protein-carboxyl O-methyltransferase, EC. 2.1.1.24) has been investigated. Ovine lutropin and adrenocorticotropin (alpha1-39-ACTH) were found to be good methyl acceptor substrates, followed by beta-lipotropin. While the alpha-subunit of lutropin had nearly equal the methyl accepting activity of lutropin, the beta-subunit was devoid of accepting activity. The maximum amount of esterification occurred between 15 and 30 min at 37 degrees C) depending on the methyl acceptor molecule. The rate of the methyl esterification of adrenocorticotropin fragments was also studied. While alpha7-38-ACTH had less than half of alpha1-37-ACTH methyl accepting capacity, alpha1-17-ACTH did not serve as methyl acceptor. However, when a mixture of the two fragments was preincubated, the resulting mixture had full alpha1-39-ACTH activity.", "contents": "Enzymatic methyl esterification of pituitary polypeptides. Methyl esterification of pituitary polypeptides by protein methylase II (S-adenosylmethionine:protein-carboxyl O-methyltransferase, EC. 2.1.1.24) has been investigated. Ovine lutropin and adrenocorticotropin (alpha1-39-ACTH) were found to be good methyl acceptor substrates, followed by beta-lipotropin. While the alpha-subunit of lutropin had nearly equal the methyl accepting activity of lutropin, the beta-subunit was devoid of accepting activity. The maximum amount of esterification occurred between 15 and 30 min at 37 degrees C) depending on the methyl acceptor molecule. The rate of the methyl esterification of adrenocorticotropin fragments was also studied. While alpha7-38-ACTH had less than half of alpha1-37-ACTH methyl accepting capacity, alpha1-17-ACTH did not serve as methyl acceptor. However, when a mixture of the two fragments was preincubated, the resulting mixture had full alpha1-39-ACTH activity."}
{"id": "PMID:218890", "title": "Adrenocorticotropin. 52 Synthesis and biological activity of adrenocorticotropic peptides with cystine bridges.", "content": "Three analogs of the amino terminal nonadecopeptide of adrenocorticotropin which incorporate cystine cystine bridges between positions (5, 10), (3, 10), or (2, 10) have been synthesized. All of the peptide analogs showed reduced biological activity; however, the peptide with the 5, 10 cystine bridge was shown to possess significantly higher lipolytic activity in rat fat cells than the peptides with a 3, 10 or 2, 10 cystine bridge.", "contents": "Adrenocorticotropin. 52 Synthesis and biological activity of adrenocorticotropic peptides with cystine bridges. Three analogs of the amino terminal nonadecopeptide of adrenocorticotropin which incorporate cystine cystine bridges between positions (5, 10), (3, 10), or (2, 10) have been synthesized. All of the peptide analogs showed reduced biological activity; however, the peptide with the 5, 10 cystine bridge was shown to possess significantly higher lipolytic activity in rat fat cells than the peptides with a 3, 10 or 2, 10 cystine bridge."}
{"id": "PMID:218891", "title": "Intratypic serodifferentiation of poliomyelitis virus strains by strain-specific antisera.", "content": "Strain-specific antisera against non-Sabin-like and Sabin-like poliovirus strains were prepared by cross-absorption of the antisera with the heterologous strain. Isolates from different parts of the world were differentiated intratypically as non-Sabin-like and Sabin-like strains with the aid of these sera in the immunodiffusion test and neutralization test. In comparison with other marker tests, intratypic differentiation can be performed more easily. Further, fewer intermediate strains were found and, in our opinion, the results are more reliable.", "contents": "Intratypic serodifferentiation of poliomyelitis virus strains by strain-specific antisera. Strain-specific antisera against non-Sabin-like and Sabin-like poliovirus strains were prepared by cross-absorption of the antisera with the heterologous strain. Isolates from different parts of the world were differentiated intratypically as non-Sabin-like and Sabin-like strains with the aid of these sera in the immunodiffusion test and neutralization test. In comparison with other marker tests, intratypic differentiation can be performed more easily. Further, fewer intermediate strains were found and, in our opinion, the results are more reliable."}
{"id": "PMID:218892", "title": "Analysis of the transformation of human lymphocytes by Epstein-Barr virus. I. Sequential occurrence from the virus-determined nuclear antigen synthesis, to blastogenesis, to DNA synthesis.", "content": "A B-cell population of human cord blood lymphocytes was exposed to the B95-8 strain of Epstein-Barr virus (EBV), and simultaneous observations of immunofluorescence, cellular morphology and autoradiography were carried out in each individual cell. It was evident that EBV-determined nuclear antigen (EBNA) synthesis occurred prior to blastogenic response and DNA synthesis. EBNA-positive cells could be observed as early as 12 h after infection and reached a maximum of 17% at 24 h, followed by a plateau for a subsequent 12 h. The positive cells were seen exclusively as morphologically normal lymphocytes until 18 h; at 24 h, blastogenesis became evident, without cell division. DNA synthesis was detected at 36 h in EBNA-positive blast cells, after which these cells increased rapidly. EBNA synthesis was similarly evident in the presence of cytosine arabinoside, but was significantly inhibited by a short-term exposure to cycloheximide immediately after infection. These findings suggest that the early events in EBV-induced transformation of human lymphocytes occur sequentially from EBNA synthesis, to blastogenesis, to DNA synthesis and that the crucial step of such transformation is probably involved in protein synthesis occurring in the very early stage of EBV infection.", "contents": "Analysis of the transformation of human lymphocytes by Epstein-Barr virus. I. Sequential occurrence from the virus-determined nuclear antigen synthesis, to blastogenesis, to DNA synthesis. A B-cell population of human cord blood lymphocytes was exposed to the B95-8 strain of Epstein-Barr virus (EBV), and simultaneous observations of immunofluorescence, cellular morphology and autoradiography were carried out in each individual cell. It was evident that EBV-determined nuclear antigen (EBNA) synthesis occurred prior to blastogenic response and DNA synthesis. EBNA-positive cells could be observed as early as 12 h after infection and reached a maximum of 17% at 24 h, followed by a plateau for a subsequent 12 h. The positive cells were seen exclusively as morphologically normal lymphocytes until 18 h; at 24 h, blastogenesis became evident, without cell division. DNA synthesis was detected at 36 h in EBNA-positive blast cells, after which these cells increased rapidly. EBNA synthesis was similarly evident in the presence of cytosine arabinoside, but was significantly inhibited by a short-term exposure to cycloheximide immediately after infection. These findings suggest that the early events in EBV-induced transformation of human lymphocytes occur sequentially from EBNA synthesis, to blastogenesis, to DNA synthesis and that the crucial step of such transformation is probably involved in protein synthesis occurring in the very early stage of EBV infection."}
{"id": "PMID:218893", "title": "Replication of herpes simplex virus in human B lymphocytes stimulated by Epstein-Barr virus.", "content": "Human B lymphocytes prepared from adult blood or cord blood by the use of neuraminidase-treated sheep red blood cells which did not respond mitogenically to phytohemagglutinin or pokeweed mitogen, responded well to the B95-8 strain of Epstein-Barr virus, but not to the P3HR-1 strain, with increased incorporation of tritiated thymidine. Replication of herpes simplex virus could be demonstrated in cultures of B lymphocytes preincubated with the B95-8 strain.", "contents": "Replication of herpes simplex virus in human B lymphocytes stimulated by Epstein-Barr virus. Human B lymphocytes prepared from adult blood or cord blood by the use of neuraminidase-treated sheep red blood cells which did not respond mitogenically to phytohemagglutinin or pokeweed mitogen, responded well to the B95-8 strain of Epstein-Barr virus, but not to the P3HR-1 strain, with increased incorporation of tritiated thymidine. Replication of herpes simplex virus could be demonstrated in cultures of B lymphocytes preincubated with the B95-8 strain."}
{"id": "PMID:218894", "title": "Geographical distribution of swine (Hsw1N1) and Hong Kong (H3N2) influenza virus variants in pigs in Southeast Asia.", "content": "Influenza viruses of the Hsw1N1 and H3N2 subtypes were isolated in Hong Kong from pigs originating from Hong Kong, People's Republic of China (PRC), Singapore, and Taiwan. The H3N2 isolates were from pigs from Hong Kong and PRC, whereas the Hsw1N1 isolates were from pigs from Hong Kong, PRC, Singapore and Taiwan. The hemagglutinins of the H3N2 isolates were similar to those of the earlier A/Hong Kong/1/68 and A/Port Chalmers/1/73 variants from man. The Hsw1N1 isolates were similar to the human A/New Jersey/8/76 virus. These studies extend the geographical range of Hsw1N1 influenza virus and suggest that pigs in southeast Asia, like those in North America, harbor Hsw1N1 influenza viruses. These findings underline the importance of pigs as potential reservoirs for future human pandemics by the continued isolation (in Asia) of H3N2 and Hsw1N1 influenza viruses.", "contents": "Geographical distribution of swine (Hsw1N1) and Hong Kong (H3N2) influenza virus variants in pigs in Southeast Asia. Influenza viruses of the Hsw1N1 and H3N2 subtypes were isolated in Hong Kong from pigs originating from Hong Kong, People's Republic of China (PRC), Singapore, and Taiwan. The H3N2 isolates were from pigs from Hong Kong and PRC, whereas the Hsw1N1 isolates were from pigs from Hong Kong, PRC, Singapore and Taiwan. The hemagglutinins of the H3N2 isolates were similar to those of the earlier A/Hong Kong/1/68 and A/Port Chalmers/1/73 variants from man. The Hsw1N1 isolates were similar to the human A/New Jersey/8/76 virus. These studies extend the geographical range of Hsw1N1 influenza virus and suggest that pigs in southeast Asia, like those in North America, harbor Hsw1N1 influenza viruses. These findings underline the importance of pigs as potential reservoirs for future human pandemics by the continued isolation (in Asia) of H3N2 and Hsw1N1 influenza viruses."}
{"id": "PMID:218895", "title": "Presence of viral particles in the salivary gland of Calomys musculinus infected with Junin virus by a natural route.", "content": "Calomys musculinus, a wild cricetid rodent, is one of the main reservoirs of Junin virus. Six of these animals were infected by being placed in close contact with animals that had been experimentally infected with the virus. They were sacrificed at 10, 15 and 20 months after contact, and their salivary glands were studied by ultrastructural, immunohistochemical and virological methods. Two animals developed chronic viremia and low titers of complement-fixing antibodies. These animals were the only ones that had high viral titers in salivary glands and blood and viral antigen and particles in salivary glands. Although some of the other animals had viremia at the beginning of the experiment, it was absent 5 months later. Complement-fixing antibodies developed in all animals. On the basis of these findings, we assumed that the salivary gland is an important site of viral synthesis and excretion. This type of chronic infection, with persistent viremia and virus shedding, is possibly important for virus perpetuation in nature and transmission to man.", "contents": "Presence of viral particles in the salivary gland of Calomys musculinus infected with Junin virus by a natural route. Calomys musculinus, a wild cricetid rodent, is one of the main reservoirs of Junin virus. Six of these animals were infected by being placed in close contact with animals that had been experimentally infected with the virus. They were sacrificed at 10, 15 and 20 months after contact, and their salivary glands were studied by ultrastructural, immunohistochemical and virological methods. Two animals developed chronic viremia and low titers of complement-fixing antibodies. These animals were the only ones that had high viral titers in salivary glands and blood and viral antigen and particles in salivary glands. Although some of the other animals had viremia at the beginning of the experiment, it was absent 5 months later. Complement-fixing antibodies developed in all animals. On the basis of these findings, we assumed that the salivary gland is an important site of viral synthesis and excretion. This type of chronic infection, with persistent viremia and virus shedding, is possibly important for virus perpetuation in nature and transmission to man."}
{"id": "PMID:218896", "title": "Growth of type 2 herpes simplex virus in newborn and adult mononuclear leukocytes.", "content": "Growth of type 2 herpes simplex virus (HSV) in newborn and adult human mononuclear leukocytes (MNL) was compared. Phytohemagglutinin stimulation of cultures for 3 days yielded comparable peak titers in newborn (10(5.3) PFU) and adult (10(5.1) PFU) MNL. Unexpectedly, 3-day cultures of unstimulated newborn MNL also substantially replicated HSV (10(4.7) PFU), whereas similarly treated unstimulated adult cells did not. Growth of HSV in freshly isolated human MNL was next investigated. MNL from 4 mothers and 6 nonpregnant adults showed no evidence of virus growth; however, leukocytes from 11 of 24 newborns (46%) supported replication. Newborn MNL manifested an increased ability to replicate HSV within 1 day of culture, whereas comparable growth in adult MNL was not achieved until the 4th day of culture. The significance of the above observations as it relates to visceral dissemination of HSV in the neonate is discussed.", "contents": "Growth of type 2 herpes simplex virus in newborn and adult mononuclear leukocytes. Growth of type 2 herpes simplex virus (HSV) in newborn and adult human mononuclear leukocytes (MNL) was compared. Phytohemagglutinin stimulation of cultures for 3 days yielded comparable peak titers in newborn (10(5.3) PFU) and adult (10(5.1) PFU) MNL. Unexpectedly, 3-day cultures of unstimulated newborn MNL also substantially replicated HSV (10(4.7) PFU), whereas similarly treated unstimulated adult cells did not. Growth of HSV in freshly isolated human MNL was next investigated. MNL from 4 mothers and 6 nonpregnant adults showed no evidence of virus growth; however, leukocytes from 11 of 24 newborns (46%) supported replication. Newborn MNL manifested an increased ability to replicate HSV within 1 day of culture, whereas comparable growth in adult MNL was not achieved until the 4th day of culture. The significance of the above observations as it relates to visceral dissemination of HSV in the neonate is discussed."}
{"id": "PMID:218897", "title": "Induction of lytic plaques by murine leukemia virus in murine sarcoma virus-transformed nonproducer mouse cells persistently infected with mouse hepatitis virus MHV-S.", "content": "Kirsten murine sarcoma virus-transformed, nonproducer BALB3T3 (K-BALB) cells were persistently infected with mouse hepatitis virus, MHV-S. The cultures developed plaques after infection with murine leukemia viruses. If the murine leukemia virus-infected cultures were further submitted to the UV-XC assay, comparable numbers of XC plaques were obtained. The sensitivity to murine leukemia viruses, as determined by the UV-XC assay, was higher in MHV-S-infected cells as compared to uninfected K-BALB cells.", "contents": "Induction of lytic plaques by murine leukemia virus in murine sarcoma virus-transformed nonproducer mouse cells persistently infected with mouse hepatitis virus MHV-S. Kirsten murine sarcoma virus-transformed, nonproducer BALB3T3 (K-BALB) cells were persistently infected with mouse hepatitis virus, MHV-S. The cultures developed plaques after infection with murine leukemia viruses. If the murine leukemia virus-infected cultures were further submitted to the UV-XC assay, comparable numbers of XC plaques were obtained. The sensitivity to murine leukemia viruses, as determined by the UV-XC assay, was higher in MHV-S-infected cells as compared to uninfected K-BALB cells."}
{"id": "PMID:218898", "title": "Reduction of 51Cr-permeability of tissue culture cells by infection with herpes simplex virus type 1.", "content": "Infection of different strains of tissue culture cells with herpes simplex virus type 1 (HSV-1) resulted in a reduced 51Cr-permeability. A stability of the cellular membrane to Triton X-100, toxic sera and HSV-specific complement-mediated immune-cytolysis could be observed simultaneously. The results differed with respect to the cell strain used in the experiments.", "contents": "Reduction of 51Cr-permeability of tissue culture cells by infection with herpes simplex virus type 1. Infection of different strains of tissue culture cells with herpes simplex virus type 1 (HSV-1) resulted in a reduced 51Cr-permeability. A stability of the cellular membrane to Triton X-100, toxic sera and HSV-specific complement-mediated immune-cytolysis could be observed simultaneously. The results differed with respect to the cell strain used in the experiments."}
{"id": "PMID:218899", "title": "Poly(adenosine diphosphate ribose) synthesis during herpes simplex virus infection.", "content": "Immediately after infection of baby hamster kidney cells with herpes simplex virus (HSV), cellular DNA synthesis was blocked, while extensive HSV DNA synthesis began. These dramatic alterations of the control mechanisms for these two DNA synthesizing systems were not accompanied by a change in the poly(adenosine diphosphate ribose) polymerase activity.", "contents": "Poly(adenosine diphosphate ribose) synthesis during herpes simplex virus infection. Immediately after infection of baby hamster kidney cells with herpes simplex virus (HSV), cellular DNA synthesis was blocked, while extensive HSV DNA synthesis began. These dramatic alterations of the control mechanisms for these two DNA synthesizing systems were not accompanied by a change in the poly(adenosine diphosphate ribose) polymerase activity."}
{"id": "PMID:218900", "title": "Effect of glucosamine on the replication of the arenavirus Jun\u00edn in Vero cells.", "content": "When Vero cells infected with Jun\u00edn virus are cultured in the presence of 16 mM glucosamine, no infectious virus is produced and no surface antigens or virions are detected. Cytoplasmic viral antigen, however, is synthesized normally.", "contents": "Effect of glucosamine on the replication of the arenavirus Jun\u00edn in Vero cells. When Vero cells infected with Jun\u00edn virus are cultured in the presence of 16 mM glucosamine, no infectious virus is produced and no surface antigens or virions are detected. Cytoplasmic viral antigen, however, is synthesized normally."}
{"id": "PMID:218901", "title": "Absence of interferon production in a newly established human cell line.", "content": "A cell line established from human embryonic lung, HEL-R66, was demonstrated to be highly susceptible to herpes simplex virus types 1 and 2, vaccinia virus, Newcastle disease virus (NDV), Japanese encephalitis virus (JEV), western equine encephalitis (WEE) virus, Sindbis virus, vesicular stomatitis virus (VSV), and rabies virus. The maximal yields of NDV, JEV, WEE virus, and rabies virus in this cell line exceeded by 2--4 logs those in control human embryonic lung cells. Inability of this cell line to produce interferon upon treatment with native and UV-irradiated forms of virogenic and lentogenic strains of NDV and with poly I:C was revealed. A refractory state to challenging VSV did not develop in HEL-R66 cells treated with the inducers. Furthermore, pretreatment of HEL-R66 cells with interferon did not potentiate the capacity to produce interferon in response to the addition of poly I:C, whereas the same treatment enhanced the production of interferon in normal human embryonic lung cells.", "contents": "Absence of interferon production in a newly established human cell line. A cell line established from human embryonic lung, HEL-R66, was demonstrated to be highly susceptible to herpes simplex virus types 1 and 2, vaccinia virus, Newcastle disease virus (NDV), Japanese encephalitis virus (JEV), western equine encephalitis (WEE) virus, Sindbis virus, vesicular stomatitis virus (VSV), and rabies virus. The maximal yields of NDV, JEV, WEE virus, and rabies virus in this cell line exceeded by 2--4 logs those in control human embryonic lung cells. Inability of this cell line to produce interferon upon treatment with native and UV-irradiated forms of virogenic and lentogenic strains of NDV and with poly I:C was revealed. A refractory state to challenging VSV did not develop in HEL-R66 cells treated with the inducers. Furthermore, pretreatment of HEL-R66 cells with interferon did not potentiate the capacity to produce interferon in response to the addition of poly I:C, whereas the same treatment enhanced the production of interferon in normal human embryonic lung cells."}
{"id": "PMID:218902", "title": "Hybridization of bovine papilloma virus type 1 and type 2 DNA to DNA from virus-induced hamster tumors and naturally occurring equine tumors.", "content": "DNAs from bovine papilloma virus(BPV)-induced hamster tumors and from equine connective tissue tumors of unknown etiology were examined for BPV DNA sequences by molecular hybridization. DNA from two distinct classes of BPV (type 1 and type 2) was labeled in vitro and used as probes. Analysis of DNA-DNA reassociation kinetics indicated that both virus types were capable of tumor induction in the hamster. DNA isolated from 6 of 7 equine tumors accelerated the reassociation of the BPV DNA probes. BPV type 1 or type 2 DNA hybridized extensively to DNA from 3 tumors, while 3 other tumors contained DNA sequences to which only a portion of the probes hybridized. Partial hybridization of probe DNAs to tumor DNA suggested the possible existence of a third BPV class.", "contents": "Hybridization of bovine papilloma virus type 1 and type 2 DNA to DNA from virus-induced hamster tumors and naturally occurring equine tumors. DNAs from bovine papilloma virus(BPV)-induced hamster tumors and from equine connective tissue tumors of unknown etiology were examined for BPV DNA sequences by molecular hybridization. DNA from two distinct classes of BPV (type 1 and type 2) was labeled in vitro and used as probes. Analysis of DNA-DNA reassociation kinetics indicated that both virus types were capable of tumor induction in the hamster. DNA isolated from 6 of 7 equine tumors accelerated the reassociation of the BPV DNA probes. BPV type 1 or type 2 DNA hybridized extensively to DNA from 3 tumors, while 3 other tumors contained DNA sequences to which only a portion of the probes hybridized. Partial hybridization of probe DNAs to tumor DNA suggested the possible existence of a third BPV class."}
{"id": "PMID:218903", "title": "Bovine enterovirus CPE at different multiplicities of infection in the absence of viral RNA synthesis.", "content": "When bovine enterovirus (BEV) RNA synthesis was inhibited by 2-(alpha-hydroxybenzyl)-benzimidazole (HBB), an increase in MOI was accompanied by an enhancement of cytopathology. Since BEV RNA synthesis is inhibited and BEV protein synthesis is allowed to proceed in the presence of HBB, these results support the concept that proteins play a role in the development of cytopathology independently of viral double-stranded RNA.", "contents": "Bovine enterovirus CPE at different multiplicities of infection in the absence of viral RNA synthesis. When bovine enterovirus (BEV) RNA synthesis was inhibited by 2-(alpha-hydroxybenzyl)-benzimidazole (HBB), an increase in MOI was accompanied by an enhancement of cytopathology. Since BEV RNA synthesis is inhibited and BEV protein synthesis is allowed to proceed in the presence of HBB, these results support the concept that proteins play a role in the development of cytopathology independently of viral double-stranded RNA."}
{"id": "PMID:218906", "title": "A case of McCune-Albright syndrome with hyperthyroidism and vitamin D-resistant rickets.", "content": "A girl aged 1 11/12 year with the unusual combination of McCune-Albright syndrome (polyostotic fibrous dysplasia, cutaneous pigmentation and precocious puberty), hyperthyroidism and vitamin D-resistant rickets is described. Urinary estrogens are increased, while serum LH and FSH responses to LH-RH are subnormal. Thyroid hormone levels in serum and 131I thyroidal uptake are increased, while TSH response to TRH is decreased. Serum phosphorus level is low and phosphate clearance high, while PTH is within normal range. Basal GH level and GH responses to various stimulations are high, but high basal GH is suppressed by oral glucose. The oral glucose tolerance test shows normal blood glucose with hypersecretion of insulin. These data suggest that the common pathogenesis of the various aspects of the syndrome is a hypersensitivity of the target organs, which include the pituitary, the thyroid, the gonads, the pancreatic islet cells and the proximal tubules of the kidney.", "contents": "A case of McCune-Albright syndrome with hyperthyroidism and vitamin D-resistant rickets. A girl aged 1 11/12 year with the unusual combination of McCune-Albright syndrome (polyostotic fibrous dysplasia, cutaneous pigmentation and precocious puberty), hyperthyroidism and vitamin D-resistant rickets is described. Urinary estrogens are increased, while serum LH and FSH responses to LH-RH are subnormal. Thyroid hormone levels in serum and 131I thyroidal uptake are increased, while TSH response to TRH is decreased. Serum phosphorus level is low and phosphate clearance high, while PTH is within normal range. Basal GH level and GH responses to various stimulations are high, but high basal GH is suppressed by oral glucose. The oral glucose tolerance test shows normal blood glucose with hypersecretion of insulin. These data suggest that the common pathogenesis of the various aspects of the syndrome is a hypersensitivity of the target organs, which include the pituitary, the thyroid, the gonads, the pancreatic islet cells and the proximal tubules of the kidney."}
{"id": "PMID:218909", "title": "Electron microscopic and cytochemical studies of rat aorta. Intracellular vesicles containing elastin- and collagen-like material.", "content": "Small, rounded vesicles with a dense core of amorphous material were observed in all cell types in the young rat aorta, that is, endothelial cells, smooth muscle cells and fibroblasts. They were particularly numerous in the Golgi complex but were also found in the cell periphery. The content of the vesicles had staining characteristics identical to those of elastin. Material of the same type was also found in cisternae on the maturing side of the dictyosomes and in vesicles budding from them. Reaction product for thiamine pyrophosphatase was present in both these structures, indicating that the Golgi complex is responsible for the formation of the dense-cored vesicles. This was further supported by the absence of reaction product for acid phosphatase in the cisternae and in the vesicles. Moreover, no uptake of exogenous markers was noted in the latter. On the basis of these findings it is suggested that the dense-cored vesicles have a secretory function and contain precursors of elastin. Elongated vesicles or profiles containing collagen fibrils were observed in smooth muscle cells and fibroblasts. In the cell periphery, these vesicles were often found to communicate with the extracellular space. Further inside the cells, they showed a close spatial relationship to the Golgi complex. Neither thiamine pyrophosphatase nor acid phosphatase activity was demonstrated in the elongated vesicles. Like the plasma membrane, their limiting membrane was positively stained for alkaline phosphatase. On the basis of these findings and the absence of uptake of exogenous markers in them, it is suggested that the elongated vesicles represent a means for collagen secretion in the growing aortic wall. The Golgi complex is believed to be involved in the transfer of collagen to these vesicles.", "contents": "Electron microscopic and cytochemical studies of rat aorta. Intracellular vesicles containing elastin- and collagen-like material. Small, rounded vesicles with a dense core of amorphous material were observed in all cell types in the young rat aorta, that is, endothelial cells, smooth muscle cells and fibroblasts. They were particularly numerous in the Golgi complex but were also found in the cell periphery. The content of the vesicles had staining characteristics identical to those of elastin. Material of the same type was also found in cisternae on the maturing side of the dictyosomes and in vesicles budding from them. Reaction product for thiamine pyrophosphatase was present in both these structures, indicating that the Golgi complex is responsible for the formation of the dense-cored vesicles. This was further supported by the absence of reaction product for acid phosphatase in the cisternae and in the vesicles. Moreover, no uptake of exogenous markers was noted in the latter. On the basis of these findings it is suggested that the dense-cored vesicles have a secretory function and contain precursors of elastin. Elongated vesicles or profiles containing collagen fibrils were observed in smooth muscle cells and fibroblasts. In the cell periphery, these vesicles were often found to communicate with the extracellular space. Further inside the cells, they showed a close spatial relationship to the Golgi complex. Neither thiamine pyrophosphatase nor acid phosphatase activity was demonstrated in the elongated vesicles. Like the plasma membrane, their limiting membrane was positively stained for alkaline phosphatase. On the basis of these findings and the absence of uptake of exogenous markers in them, it is suggested that the elongated vesicles represent a means for collagen secretion in the growing aortic wall. The Golgi complex is believed to be involved in the transfer of collagen to these vesicles."}
{"id": "PMID:218910", "title": "Phosphatases in the central nervous system of spiders (Arachnida, Araneae).", "content": "The central nervous systems of web-building spiders (Araneidae, Agelenidae) and hunting spiders (Lycosidae, Salticidae) were tested for non-specific and specific phosphatases. Acid phosphatase exhibited weakly to moderately positive reactions in the neuronal cell bodies and in the neuropile fibre mass of all species investigated. Alkaline phosphatase could only be demonstrated in the external and internal neural lamellae of the brain and ventral cord of several specimens of the araneid species investigated. Tests for thiamine pyrophosphatase were negative with both the lead and calcium-cobalt methods. Distinctive positive reactions for adenosine triphosphatase were visible in the nervous system of all the species used, being especially strong in the optic ganglia of the hunting spiders. The demonstration of adenosine triphosphatase was only possible when applying the calcium-cobalt method after Padykula and Herman, while the lead method after Wachstein and Meisel did not produce any staining reaction at all. Controls of the histochemical reaction showed that the enzyme was activated by Ca2+ and inhibited by sulphydryl destroying reagents (e.g. PCMB), but was insensitive to ouabain. It could be probably classified as a mitochondrial proton-translocating adenosine triphosphatase.", "contents": "Phosphatases in the central nervous system of spiders (Arachnida, Araneae). The central nervous systems of web-building spiders (Araneidae, Agelenidae) and hunting spiders (Lycosidae, Salticidae) were tested for non-specific and specific phosphatases. Acid phosphatase exhibited weakly to moderately positive reactions in the neuronal cell bodies and in the neuropile fibre mass of all species investigated. Alkaline phosphatase could only be demonstrated in the external and internal neural lamellae of the brain and ventral cord of several specimens of the araneid species investigated. Tests for thiamine pyrophosphatase were negative with both the lead and calcium-cobalt methods. Distinctive positive reactions for adenosine triphosphatase were visible in the nervous system of all the species used, being especially strong in the optic ganglia of the hunting spiders. The demonstration of adenosine triphosphatase was only possible when applying the calcium-cobalt method after Padykula and Herman, while the lead method after Wachstein and Meisel did not produce any staining reaction at all. Controls of the histochemical reaction showed that the enzyme was activated by Ca2+ and inhibited by sulphydryl destroying reagents (e.g. PCMB), but was insensitive to ouabain. It could be probably classified as a mitochondrial proton-translocating adenosine triphosphatase."}
{"id": "PMID:218911", "title": "ACTH radioimmunocytochemistry (RICH) on rat anterior pituitary cells.", "content": "Radioimmunocytochemistry (RICH) was applied to detect corticotrophs in adult rat pituitaries and 8-day-old anterior pituitary monolayers by incubating sections and cultures with 125I-ACTH-anti ACTH immune complexes. After incubations autoradiography was made. In comparison, \"conventional\" immunostaining was carried out on adjacent sections and parallel cultures. It has been established that RICH is suitable for detection of corticotrophs.", "contents": "ACTH radioimmunocytochemistry (RICH) on rat anterior pituitary cells. Radioimmunocytochemistry (RICH) was applied to detect corticotrophs in adult rat pituitaries and 8-day-old anterior pituitary monolayers by incubating sections and cultures with 125I-ACTH-anti ACTH immune complexes. After incubations autoradiography was made. In comparison, \"conventional\" immunostaining was carried out on adjacent sections and parallel cultures. It has been established that RICH is suitable for detection of corticotrophs."}
{"id": "PMID:218912", "title": "Cytochemical analysis of organelle degradation in phagosomes and apoptotic cells of the mucoid epithelium of mice.", "content": "The activity of mitochondrial cytochrome oxidase and peroxisomal catalase in the phagolysosomes and apoptotic bodies of mucoid epithelial cells was analysed. Tissue from 2-6 day old mice was used. The activity of acid phosphatase in lysosomes was also estimated. Cytochrome oxidase was demonstrated in well-preserved mitochondria inside phagosomes. Mitochondria in cells exhibiting apoptotic death also show activity of cytochrome oxidase. The enzyme activity in swollen mitochondria ceases before the membranes of the cristae disappear completely. Apoptotic bodies are phagocytosed by sister mucoid cells and, later on, they are digested inside the cell. Phagosomes which contain already degraded mitochondria show still active catalase in sequestered peroxisomes. The acid phosphatase involved in degradation of phagocytosed material originates from endocytosed lysosomes and primary and secondary lysosomes which fuse with the membranes of phagosomes.", "contents": "Cytochemical analysis of organelle degradation in phagosomes and apoptotic cells of the mucoid epithelium of mice. The activity of mitochondrial cytochrome oxidase and peroxisomal catalase in the phagolysosomes and apoptotic bodies of mucoid epithelial cells was analysed. Tissue from 2-6 day old mice was used. The activity of acid phosphatase in lysosomes was also estimated. Cytochrome oxidase was demonstrated in well-preserved mitochondria inside phagosomes. Mitochondria in cells exhibiting apoptotic death also show activity of cytochrome oxidase. The enzyme activity in swollen mitochondria ceases before the membranes of the cristae disappear completely. Apoptotic bodies are phagocytosed by sister mucoid cells and, later on, they are digested inside the cell. Phagosomes which contain already degraded mitochondria show still active catalase in sequestered peroxisomes. The acid phosphatase involved in degradation of phagocytosed material originates from endocytosed lysosomes and primary and secondary lysosomes which fuse with the membranes of phagosomes."}
{"id": "PMID:218913", "title": "Isolation of intramitochondrial bodies in bovine adrenocortical cells by density gradient centrifugation.", "content": "Two method for isolating the intramitochondrial bodies from bovine adrenocortical cells are proposed. Electron microscopic examination shows that discontinuous sucrose density gradient centrifugation can separate the fraction rich in intramitochondrial bodies, but some indistinguishable fragments remain among them. Continuous sucrose density gradient centrifugation is probably superior to the former method in obtaining a highly purified fraction of the bodies. The amido black positive granules, presumed to be intramitochondrial bodies, are collected in the fractions of the sucrose density of around 1.27 (1.23--1.30), which lack cytochrome c oxidase activity.", "contents": "Isolation of intramitochondrial bodies in bovine adrenocortical cells by density gradient centrifugation. Two method for isolating the intramitochondrial bodies from bovine adrenocortical cells are proposed. Electron microscopic examination shows that discontinuous sucrose density gradient centrifugation can separate the fraction rich in intramitochondrial bodies, but some indistinguishable fragments remain among them. Continuous sucrose density gradient centrifugation is probably superior to the former method in obtaining a highly purified fraction of the bodies. The amido black positive granules, presumed to be intramitochondrial bodies, are collected in the fractions of the sucrose density of around 1.27 (1.23--1.30), which lack cytochrome c oxidase activity."}
{"id": "PMID:218914", "title": "Histochemical demonstration of mercury induced changes in rat neurons.", "content": "A histochemical method modified for ultrastructural studies of mercury induced changes is described. Rat neurons from areas known to be influenced by mercury are used as examples. The histochemical reaction, suggested to be caused by polymercury sulphide complexes, is localized to \"dense bodies\" where it is visible 14 days after initiation of peroral mercury treatment (20 mg HgCl2/l drinking water).", "contents": "Histochemical demonstration of mercury induced changes in rat neurons. A histochemical method modified for ultrastructural studies of mercury induced changes is described. Rat neurons from areas known to be influenced by mercury are used as examples. The histochemical reaction, suggested to be caused by polymercury sulphide complexes, is localized to \"dense bodies\" where it is visible 14 days after initiation of peroral mercury treatment (20 mg HgCl2/l drinking water)."}
{"id": "PMID:218915", "title": "Activities of malate dehydrogenase, 3-hydroxyacyl-CoA dehydrogenase and fructose-1,6-diphosphatase with regard to metabolic subpopulations of fast- and slow-twitch fibres in rabbit muscles.", "content": "Activities of malate dehydrogenase (MDH), 3-hydroxyacyl-CoA dehydrogenase (HAD) and fructose-1,6-diphosphatase (FDPase) were determined in single fibres dissected from freeze-dried rabbit psoas and soleus muscles. Slow-twitch fibres as determined by qualitative ATPase reaction represent a rather uniform population with regard to HAD and MDH activities. In these fibres the two enzymes are in constant proportions. FDPase is found at extremely low activities in slow-twitch fibres and because of its relatively high activity in fast-twitch fibres of soleus and psoas muscle it might be used as a marker enzyme. Fast-twitch fibres in psoas muscle represent a heterogeneous population with regard to activities of MDH as well as of HAD. The two enzyme activities are not proportional in fast-twitch psoas fibres. These findings suggest the existence of metabolic subpopulations of fast-twitch fibres having a wide range of aerobic oxidative capacities and having differences in their capacity to oxidizing fatty acids.", "contents": "Activities of malate dehydrogenase, 3-hydroxyacyl-CoA dehydrogenase and fructose-1,6-diphosphatase with regard to metabolic subpopulations of fast- and slow-twitch fibres in rabbit muscles. Activities of malate dehydrogenase (MDH), 3-hydroxyacyl-CoA dehydrogenase (HAD) and fructose-1,6-diphosphatase (FDPase) were determined in single fibres dissected from freeze-dried rabbit psoas and soleus muscles. Slow-twitch fibres as determined by qualitative ATPase reaction represent a rather uniform population with regard to HAD and MDH activities. In these fibres the two enzymes are in constant proportions. FDPase is found at extremely low activities in slow-twitch fibres and because of its relatively high activity in fast-twitch fibres of soleus and psoas muscle it might be used as a marker enzyme. Fast-twitch fibres in psoas muscle represent a heterogeneous population with regard to activities of MDH as well as of HAD. The two enzyme activities are not proportional in fast-twitch psoas fibres. These findings suggest the existence of metabolic subpopulations of fast-twitch fibres having a wide range of aerobic oxidative capacities and having differences in their capacity to oxidizing fatty acids."}
{"id": "PMID:218916", "title": "Bent-limb syndrome in lambs raised in total confinement.", "content": "A bent-limb syndrome in lambs raised in total confinement was characterized by curvature of the forelimbs. Radiographic findings included flaring of the affected long bone and thinning of the growth plate. The main histologic change was endochondral dysplasia of the long bone. In feed samples, all trace minerals analyzed were within recommended concentrations except iron, which was much higher (400 ppm dry matter) than the normal requirement of lambs (70 ppm). All mineral concentrations in serum were normal except those of inorganic phosphorus and iron, which were higher. Results of soft tissue and bone mineral analyses were normal. Altering the ratio of calcium and phosphorus did not affect the incidence of disease, but intramuscular administration of massive doses of vitamin D3 and reducing the amount of dietary iron had a prophylactic effect. The increase in serum phosphorus was probably related to the dietary excess of iron, which probably decreased vitamin D metabolite formation in the kidney, which in turn could be prevented by massive doses of vitamin D3.", "contents": "Bent-limb syndrome in lambs raised in total confinement. A bent-limb syndrome in lambs raised in total confinement was characterized by curvature of the forelimbs. Radiographic findings included flaring of the affected long bone and thinning of the growth plate. The main histologic change was endochondral dysplasia of the long bone. In feed samples, all trace minerals analyzed were within recommended concentrations except iron, which was much higher (400 ppm dry matter) than the normal requirement of lambs (70 ppm). All mineral concentrations in serum were normal except those of inorganic phosphorus and iron, which were higher. Results of soft tissue and bone mineral analyses were normal. Altering the ratio of calcium and phosphorus did not affect the incidence of disease, but intramuscular administration of massive doses of vitamin D3 and reducing the amount of dietary iron had a prophylactic effect. The increase in serum phosphorus was probably related to the dietary excess of iron, which probably decreased vitamin D metabolite formation in the kidney, which in turn could be prevented by massive doses of vitamin D3."}
{"id": "PMID:218917", "title": "Serologic survey of prevalence of ovine progressive pneumonia in Idaho range sheep.", "content": "Blood samples from 2,310 mature sheep in 3 Idaho range flocks were examined by agar gel immunodiffusion to determine the prevalence of ovine progressive pneumonia. The prevalence ranged from 58% for all ages combined in one flock to 90% of cull ewes in another flock. Age-specific prevalence rates increased from 16% in yearlings to 83% in ewes greater than or equal to 7 years old. Rambouillet sheep had a significantly (P less than 0.01) lower prevalence than sheep of 5 other breeds, whereas one-half Finnsheep crosses had a significantly (P less than 0.01) higher prevalence than sheep of other breeds. Within breed and age, there was no significant difference in reproductive performance between seropositive and seronegative ewes.", "contents": "Serologic survey of prevalence of ovine progressive pneumonia in Idaho range sheep. Blood samples from 2,310 mature sheep in 3 Idaho range flocks were examined by agar gel immunodiffusion to determine the prevalence of ovine progressive pneumonia. The prevalence ranged from 58% for all ages combined in one flock to 90% of cull ewes in another flock. Age-specific prevalence rates increased from 16% in yearlings to 83% in ewes greater than or equal to 7 years old. Rambouillet sheep had a significantly (P less than 0.01) lower prevalence than sheep of 5 other breeds, whereas one-half Finnsheep crosses had a significantly (P less than 0.01) higher prevalence than sheep of other breeds. Within breed and age, there was no significant difference in reproductive performance between seropositive and seronegative ewes."}
{"id": "PMID:218918", "title": "Diagnostic features of ovine progressive pneumonia.", "content": "Ovine progressive pneumonia, a chronic, insidious disease of adult sheep, has a relentless course leading to dyspnea, emaciation, and death. Clinical observations and serologic tests are adequate for making a tentative diagnosis. The agar gel immunodiffusion test seems to be the best serologic procedure for indicating infection with the virus but cannot be used to predict morphologic changes or clinical disease, inasmuch as many clinically unaffected animals carry the virus. A definitive diagnosis is based on finding lesions and isolating virus. Affected lungs are large and heavy as a result of interstitial accumulation of lymphoid cells and fibromuscular tissue. Frequently, interstitial lesions are accompanied by bronchopneumonia from secondary bacterial infection. The causal virus can be isolated from infected lungs by cocultivation with primary ovine or bovine cells.", "contents": "Diagnostic features of ovine progressive pneumonia. Ovine progressive pneumonia, a chronic, insidious disease of adult sheep, has a relentless course leading to dyspnea, emaciation, and death. Clinical observations and serologic tests are adequate for making a tentative diagnosis. The agar gel immunodiffusion test seems to be the best serologic procedure for indicating infection with the virus but cannot be used to predict morphologic changes or clinical disease, inasmuch as many clinically unaffected animals carry the virus. A definitive diagnosis is based on finding lesions and isolating virus. Affected lungs are large and heavy as a result of interstitial accumulation of lymphoid cells and fibromuscular tissue. Frequently, interstitial lesions are accompanied by bronchopneumonia from secondary bacterial infection. The causal virus can be isolated from infected lungs by cocultivation with primary ovine or bovine cells."}
{"id": "PMID:218919", "title": "Pancreatic islet cell adenocarcinoma: clinical and diagnostic features of six cases.", "content": "The clinicopathologic aspects of pancreatic islet cell adenocarcinoma in 6 dogs were compared. Diagnosis was based on insulin-glucose ratios in 5 dogs. Surgical excision of the tumor resulted in absence of clinical signs for at least 1 year in 3 dogs.", "contents": "Pancreatic islet cell adenocarcinoma: clinical and diagnostic features of six cases. The clinicopathologic aspects of pancreatic islet cell adenocarcinoma in 6 dogs were compared. Diagnosis was based on insulin-glucose ratios in 5 dogs. Surgical excision of the tumor resulted in absence of clinical signs for at least 1 year in 3 dogs."}
{"id": "PMID:218921", "title": "Structure of bonito heart ferricytochrome c and some remarks on molecular interaction in its crystalline state.", "content": "The structure analysis of bonito heart ferricytochrome c was carried out at 2.8 A resolution by X-ray diffraction. The overall features of the molecule are virtually identical with those of bonito ferrocytochromes c and other cytochromes c. In the present work, the modes of molecular packing among cytochromes c were also compared by means of intermolecular distance maps. Some differences in the structures of ferro- and ferricytochrome c may exist on the surface of the molecules.", "contents": "Structure of bonito heart ferricytochrome c and some remarks on molecular interaction in its crystalline state. The structure analysis of bonito heart ferricytochrome c was carried out at 2.8 A resolution by X-ray diffraction. The overall features of the molecule are virtually identical with those of bonito ferrocytochromes c and other cytochromes c. In the present work, the modes of molecular packing among cytochromes c were also compared by means of intermolecular distance maps. Some differences in the structures of ferro- and ferricytochrome c may exist on the surface of the molecules."}
{"id": "PMID:218923", "title": "Phosphodiesterase-phosphomonesterases from Fusarium moniliforme. Separation and properties of four isozymes.", "content": "Purified phosphodiesterase-phosphomonoesterase was found to be composed of four isozymes with different isoelectric points. These isozymes, phosphodiesterase-phosphomonoesterases 1-4, were separated from one another by repeated isoelectric focusing. Very little difference in amino acid composition, enzymic properties or circular dichroism spectra was detected among the isozymes. Far-ultraviolet circular dichroism spectra showed that the enzyme contained about 10% alpha-helix and 40% beta-structure. Phosphodiesterase-phosphomonesterase is a glycoprotein, because it was adsorbed on concanavalin A-Sepharose 4B and gave a band of carbohydrate coincident with that of protein or enzymic activity on polyacrylamide disc gel electrophoresis. Carbohydrate analyses revealed that the enzyme contained 37 micron of N-acetylglucosamine and 358 micron of mannose per mg of protein. The carbohydrate contents of the four isozymes were almost the same.", "contents": "Phosphodiesterase-phosphomonesterases from Fusarium moniliforme. Separation and properties of four isozymes. Purified phosphodiesterase-phosphomonoesterase was found to be composed of four isozymes with different isoelectric points. These isozymes, phosphodiesterase-phosphomonoesterases 1-4, were separated from one another by repeated isoelectric focusing. Very little difference in amino acid composition, enzymic properties or circular dichroism spectra was detected among the isozymes. Far-ultraviolet circular dichroism spectra showed that the enzyme contained about 10% alpha-helix and 40% beta-structure. Phosphodiesterase-phosphomonesterase is a glycoprotein, because it was adsorbed on concanavalin A-Sepharose 4B and gave a band of carbohydrate coincident with that of protein or enzymic activity on polyacrylamide disc gel electrophoresis. Carbohydrate analyses revealed that the enzyme contained 37 micron of N-acetylglucosamine and 358 micron of mannose per mg of protein. The carbohydrate contents of the four isozymes were almost the same."}
{"id": "PMID:218925", "title": "Studies on nitrate reductase of Clostridium perfringens. II. Purification and some properties of ferredoxin.", "content": "A ferredoxin was purified from Clostridium perfringens by DEAE-cellulose chromatography and Sephadex G-50 gel filtration. It had absorption maxima at 390 and 280 nm. The molecular weight was estimated to be 6,000 by Sephadex gel filtration and from the results of amino acid analysis. The isoelectric point was 3.0. It contained four atoms of iron, four atoms of labile sulfur, and six cysteine residues. This ferredoxin as well as ferredoxin from C. pasteurianum acted as an electron donor for nitrate reductase from C. perfringens. The ferredoxin could also act as an electron donor for the hydrogenase from C. pasteurianum in hydrogen evolution.", "contents": "Studies on nitrate reductase of Clostridium perfringens. II. Purification and some properties of ferredoxin. A ferredoxin was purified from Clostridium perfringens by DEAE-cellulose chromatography and Sephadex G-50 gel filtration. It had absorption maxima at 390 and 280 nm. The molecular weight was estimated to be 6,000 by Sephadex gel filtration and from the results of amino acid analysis. The isoelectric point was 3.0. It contained four atoms of iron, four atoms of labile sulfur, and six cysteine residues. This ferredoxin as well as ferredoxin from C. pasteurianum acted as an electron donor for nitrate reductase from C. perfringens. The ferredoxin could also act as an electron donor for the hydrogenase from C. pasteurianum in hydrogen evolution."}
{"id": "PMID:218926", "title": "ADP ribosylation of rat liver nucleosomal core histones.", "content": "When nucleosomal core histones were isolated from rat liver nuclei incubated with [14C]NAD+ and fractionated into the individual components (H2A, H2B, H3, and H4), [14C]adenosine diphosphate ribose (ADP-Rib) was found to be associated with all of them. However, while about 15% of the H2B molecules were modified, less than 2% of the other fractions contained radioactive ADP-Rib. The nucleotide attached to H2B was identified as a single monomer of ADP-Rib. On subjectint H2B to electrophoresis in polyacrylamide gels containing 2.5 M urea and 0.9 N acetic acid, one single band of H2B with 5% less mobility than the unomdified control was obtained. The linkage between H2B and ADP-Rib was rapidly hydrolyzed with 0.1 N NaOH or with 1 M neutral hydroxylamine. Hydrolysis of ADP-ribosylated H2B with trypsin generated a single peptide linked to ADP-Rib, which corresponded to the sequence Pro-Glu-Pro-Ala-Lys. We were able to dansylate the NH2-terminal proline, which proved that the imino group of this amino acid was not substituted. These findings, together with the chemical properties of the linkage, which were typical of those of an ester-like bond, strongly suggest that the ADP-Rib residue was linked to the gamma-COOH group of the glutamic acid in position 2 of H2B.", "contents": "ADP ribosylation of rat liver nucleosomal core histones. When nucleosomal core histones were isolated from rat liver nuclei incubated with [14C]NAD+ and fractionated into the individual components (H2A, H2B, H3, and H4), [14C]adenosine diphosphate ribose (ADP-Rib) was found to be associated with all of them. However, while about 15% of the H2B molecules were modified, less than 2% of the other fractions contained radioactive ADP-Rib. The nucleotide attached to H2B was identified as a single monomer of ADP-Rib. On subjectint H2B to electrophoresis in polyacrylamide gels containing 2.5 M urea and 0.9 N acetic acid, one single band of H2B with 5% less mobility than the unomdified control was obtained. The linkage between H2B and ADP-Rib was rapidly hydrolyzed with 0.1 N NaOH or with 1 M neutral hydroxylamine. Hydrolysis of ADP-ribosylated H2B with trypsin generated a single peptide linked to ADP-Rib, which corresponded to the sequence Pro-Glu-Pro-Ala-Lys. We were able to dansylate the NH2-terminal proline, which proved that the imino group of this amino acid was not substituted. These findings, together with the chemical properties of the linkage, which were typical of those of an ester-like bond, strongly suggest that the ADP-Rib residue was linked to the gamma-COOH group of the glutamic acid in position 2 of H2B."}
{"id": "PMID:218927", "title": "Cell-free synthesis of mouse corticotropin. Evidence for two high molecular weight gene products.", "content": "Polysomes or mRNA prepared from cultured AtT-20/D16v mouse pituitary adenocarcinoma cells direct the efficient incorporation of amino acid into newly synthesized material in the presence of wheat germ translational factors. A significant franction of the total cell-free product is specifically immunoprecipitable with corticotropin antibody purified by immune affinity chromatography. Analysis of the cell-free synthesized immunoreactive products by sodium dodecyl sulfate-polyacrylamide gel electrophoresis reveals that two high molecular weight corticotropin species (Mr congruent to 32,500 and 28,000) are synthesized in an approximate 2:1 ratio. Neither product contains carbohydrate based upon concanavalin A chromatography or exposure to polysaccharidases. The smaller molecular weight product does not appear to arise from proteolytic processing since both species are synthesized in approximately the same ratio in cell-free reaction mixtures directed by either polysomes or mRNA. These results suggest that AtT-20/D16v cells contain two distinct mRNA poluations specifying the synthesis of two different high molecular weight forms of mouse corticotropin.", "contents": "Cell-free synthesis of mouse corticotropin. Evidence for two high molecular weight gene products. Polysomes or mRNA prepared from cultured AtT-20/D16v mouse pituitary adenocarcinoma cells direct the efficient incorporation of amino acid into newly synthesized material in the presence of wheat germ translational factors. A significant franction of the total cell-free product is specifically immunoprecipitable with corticotropin antibody purified by immune affinity chromatography. Analysis of the cell-free synthesized immunoreactive products by sodium dodecyl sulfate-polyacrylamide gel electrophoresis reveals that two high molecular weight corticotropin species (Mr congruent to 32,500 and 28,000) are synthesized in an approximate 2:1 ratio. Neither product contains carbohydrate based upon concanavalin A chromatography or exposure to polysaccharidases. The smaller molecular weight product does not appear to arise from proteolytic processing since both species are synthesized in approximately the same ratio in cell-free reaction mixtures directed by either polysomes or mRNA. These results suggest that AtT-20/D16v cells contain two distinct mRNA poluations specifying the synthesis of two different high molecular weight forms of mouse corticotropin."}
{"id": "PMID:218928", "title": "Deoxyguanosine kinase. Distinct molecular forms in mitochondria and cytosol.", "content": "Two distinct deoxyguanosine kinase activities have been identified in calf thymus tissue. They can be differentiated by subcellular location, electrophoretic mobility, chromatographic behavior, nucleoside specificity, apparent Km values, and end product inhibition. After a 130-fold purification from mitochondrial extract, the newly discovered kinase was specific primarily for deoxyguanosine and deoxyinosine. Unlike the cytosol enzyme, which proved to be the broadly specific deoxycytidine kinase studied previously, the mitochondrial enzyme does not phosphorylate deoxycytidine. Its apparent Km for deoxyguanosine, 6 micromolar, is 2 orders of magnitude lower than that of the cytosol enzyme. The mitochondrial enzyme is strongly inhibited by dGTP and dITP and activated up to 6-fold by dTDP and UDP, whereas neither dCTP nor dATP had much effect.", "contents": "Deoxyguanosine kinase. Distinct molecular forms in mitochondria and cytosol. Two distinct deoxyguanosine kinase activities have been identified in calf thymus tissue. They can be differentiated by subcellular location, electrophoretic mobility, chromatographic behavior, nucleoside specificity, apparent Km values, and end product inhibition. After a 130-fold purification from mitochondrial extract, the newly discovered kinase was specific primarily for deoxyguanosine and deoxyinosine. Unlike the cytosol enzyme, which proved to be the broadly specific deoxycytidine kinase studied previously, the mitochondrial enzyme does not phosphorylate deoxycytidine. Its apparent Km for deoxyguanosine, 6 micromolar, is 2 orders of magnitude lower than that of the cytosol enzyme. The mitochondrial enzyme is strongly inhibited by dGTP and dITP and activated up to 6-fold by dTDP and UDP, whereas neither dCTP nor dATP had much effect."}
{"id": "PMID:218931", "title": "Modification of human placental lactogen with plasmin. Preparation and characterization of a modified hormone with increased biologic activity.", "content": "To determine the structure needed for the biologic activity of human placental lactogen (hPL), we have cleaved hPL with the proteolytic enzyme plasmin. Plasmin modified hPL (PL-hPL) was purified by gel chromatography. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis before and after reduction showed that cleavage had occurred within the Cys53-Cys165 loop and tryptic peptide maps revealed that a single peptide consisting of residues 135 to 140 had been removed. 5-Dimethylaminonaphthalene-1-sulfonyl end group analysis and digestion with carboxypeptidase B confirmed that cleavage was complete and only the single hexapeptide was removed. In a membrane binding assay for lactogenic activity PL-hPL was 2- to 3-fold more potent than hPL. Using growth hormone receptors from rabbit liver membranes, PL-hPL was also more potent than hPL, but still much less potent than growth hormone. The lactogenic activity of PL-hPL in an in vitro bioassay was 75% above that of unmodified hormone. It is concluded that plasmin cleaves homologous peptides from hPL and growth hormone and that removal of the hexapeptide from hPL results in enhanced biologic activity.", "contents": "Modification of human placental lactogen with plasmin. Preparation and characterization of a modified hormone with increased biologic activity. To determine the structure needed for the biologic activity of human placental lactogen (hPL), we have cleaved hPL with the proteolytic enzyme plasmin. Plasmin modified hPL (PL-hPL) was purified by gel chromatography. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis before and after reduction showed that cleavage had occurred within the Cys53-Cys165 loop and tryptic peptide maps revealed that a single peptide consisting of residues 135 to 140 had been removed. 5-Dimethylaminonaphthalene-1-sulfonyl end group analysis and digestion with carboxypeptidase B confirmed that cleavage was complete and only the single hexapeptide was removed. In a membrane binding assay for lactogenic activity PL-hPL was 2- to 3-fold more potent than hPL. Using growth hormone receptors from rabbit liver membranes, PL-hPL was also more potent than hPL, but still much less potent than growth hormone. The lactogenic activity of PL-hPL in an in vitro bioassay was 75% above that of unmodified hormone. It is concluded that plasmin cleaves homologous peptides from hPL and growth hormone and that removal of the hexapeptide from hPL results in enhanced biologic activity."}
{"id": "PMID:218939", "title": "Regulatory interactions between mitochondrial genes. I. Genetic and biochemical characterization of some mutant types affecting apocytochrome b and cytochrome oxidase.", "content": "The region of the mtDNA containing the structural gene for apocytochrome b is called the cob or box region. There is evidence that the same region is also involved in the regulation of cytochrome oxidase. We have isolated eight mit- mutants in this region and have ordered them using petite deletion mapping. Four of these mutants appear to map outside the boxII region on the oli2-proximal end. Analysis of restriction endonuclease fragments of the mtDNA from peptides used in the deletion mapping suggests a minimum size of 3.1 x 10(3) base pairs for the whole cob region. Although none of our mutants contained any cytochrome b or cytochrome b-linked activities, polypeptides apparently related to apocytochrome b were present in some but not all mutants. Additional regulatory effects (both positive and negative) on cytochrome oxidase by virtue of control of its subunit I were also observed. In addition to these phenotypic traits, some of the mutants accumulated novel, mitochondrially translated polypeptides not seen in wild type.", "contents": "Regulatory interactions between mitochondrial genes. I. Genetic and biochemical characterization of some mutant types affecting apocytochrome b and cytochrome oxidase. The region of the mtDNA containing the structural gene for apocytochrome b is called the cob or box region. There is evidence that the same region is also involved in the regulation of cytochrome oxidase. We have isolated eight mit- mutants in this region and have ordered them using petite deletion mapping. Four of these mutants appear to map outside the boxII region on the oli2-proximal end. Analysis of restriction endonuclease fragments of the mtDNA from peptides used in the deletion mapping suggests a minimum size of 3.1 x 10(3) base pairs for the whole cob region. Although none of our mutants contained any cytochrome b or cytochrome b-linked activities, polypeptides apparently related to apocytochrome b were present in some but not all mutants. Additional regulatory effects (both positive and negative) on cytochrome oxidase by virtue of control of its subunit I were also observed. In addition to these phenotypic traits, some of the mutants accumulated novel, mitochondrially translated polypeptides not seen in wild type."}
{"id": "PMID:218940", "title": "Regulatory interaction between mitochondrial genes. II. Detailed characterization of novel mutants mapping within one cluster in the cob2 region.", "content": "These studies describe the properties of three mit- mutants designated EM17, EM25, and PZ1, all mapping at two closely linked sites near one of the boundaries of the region of the mitochondrial genome concerned with the specification of cytochrome b. They all exhibit complex phenotypes affecting cytochrome b, cytochrome aa3, and additional polypeptides not found in the wild type. In the case of EM 17 this complexity can be ascribed to the presence of two mutations induced in the course of the initial mutagenic treatment: one, the cob2 mutation proper, is responsible for the loss of cytochrome b which is replaced by an altered, functionally inactive polypeptide, cytochrome b. This polypeptide can be further modified, or even eliminated, by the controlled introduction of another mutation in the cob1 segment of the cob region. The reduction in cytochrome oxidase subunit I, responsible for the effects on cytochrome aa3 and enzymatic activity in EM17, is due to a second (not mit-) mutation that has been located in the par1-proximal segment of the oxi3 region. This second mutation as well as the cob mutation can be overcome, and the respective aspect of wild type function restored to EM17, by recombination with rho- strains retaining the appropriate segment(s) of the wild type genome. The phenotype of the other two mutants is due to a single mutagenic event. This conclusion is confirmed by their ability to restore wild type functions by reversion. The mutation in EM25 appears to be due to a frameshift, which has led to premature chain termination, producing a polypeptide of Mr = 15,000 related to apocytochrome b. This change is accompanied by a decrease in the amount of subunit I of cytochrome oxidase. Revertants fall into three classes: on galactose two produce a polypeptide indistinguishable from apocytochrome b, but vary in its amount, while the third fails to increase apocytochrome b above mutant levels. Production of subunit I is increased but fails to reach wild type levels. Complete restoration of wild type functions can, however, be obtained by recombination of EM25 with rho- (cob2+) strains. Mutation PZ1 results in a complete absence of any polypeptide related to apocytochrome b and of cytochrome oxidase subunit I. These cells produce a novel polypeptide with a Mr = 45,000 not found in the wild type, and unrelated to all its normal polypeptides. Reversion or recombination with rho- (cob2+) strains results in virtually complete restoration of all wild type functions and the elimination of the novel polypeptide.", "contents": "Regulatory interaction between mitochondrial genes. II. Detailed characterization of novel mutants mapping within one cluster in the cob2 region. These studies describe the properties of three mit- mutants designated EM17, EM25, and PZ1, all mapping at two closely linked sites near one of the boundaries of the region of the mitochondrial genome concerned with the specification of cytochrome b. They all exhibit complex phenotypes affecting cytochrome b, cytochrome aa3, and additional polypeptides not found in the wild type. In the case of EM 17 this complexity can be ascribed to the presence of two mutations induced in the course of the initial mutagenic treatment: one, the cob2 mutation proper, is responsible for the loss of cytochrome b which is replaced by an altered, functionally inactive polypeptide, cytochrome b. This polypeptide can be further modified, or even eliminated, by the controlled introduction of another mutation in the cob1 segment of the cob region. The reduction in cytochrome oxidase subunit I, responsible for the effects on cytochrome aa3 and enzymatic activity in EM17, is due to a second (not mit-) mutation that has been located in the par1-proximal segment of the oxi3 region. This second mutation as well as the cob mutation can be overcome, and the respective aspect of wild type function restored to EM17, by recombination with rho- strains retaining the appropriate segment(s) of the wild type genome. The phenotype of the other two mutants is due to a single mutagenic event. This conclusion is confirmed by their ability to restore wild type functions by reversion. The mutation in EM25 appears to be due to a frameshift, which has led to premature chain termination, producing a polypeptide of Mr = 15,000 related to apocytochrome b. This change is accompanied by a decrease in the amount of subunit I of cytochrome oxidase. Revertants fall into three classes: on galactose two produce a polypeptide indistinguishable from apocytochrome b, but vary in its amount, while the third fails to increase apocytochrome b above mutant levels. Production of subunit I is increased but fails to reach wild type levels. Complete restoration of wild type functions can, however, be obtained by recombination of EM25 with rho- (cob2+) strains. Mutation PZ1 results in a complete absence of any polypeptide related to apocytochrome b and of cytochrome oxidase subunit I. These cells produce a novel polypeptide with a Mr = 45,000 not found in the wild type, and unrelated to all its normal polypeptides. Reversion or recombination with rho- (cob2+) strains results in virtually complete restoration of all wild type functions and the elimination of the novel polypeptide."}
{"id": "PMID:218941", "title": "Resolution of the phosphorylated and dephosphorylated cAMP-binding proteins of bovine cardiac muscle by affinity labeling and two-dimensional electrophoresis.", "content": "The photoaffinity label 8-azido[32P]adenosine 3':5'-monophosphate (8-azido-cyclic [32P]AMP) was used to analyze both the cAMP-binding component of the purified cAMP-dependent protein kinase, and the cAMP-binding proteins present in crude tissue extracts of bovine cardiac muscle. 8-Azido-cyclic [32P]AMP reacted specifically and in stoichiometric amounts with the cAMP-binding proteins of bovine cardiac muscle. Upon phosphorylation, the purified cAMP-binding protein from bovine cardiac muscle changed its electrophoretic mobility on sodium dodecyl sulfate-polyacrylamide gels from an apparent molecular weight of 54,000 to an apparent molecular weight of 56,000. In tissue extracts of bovine cardiac muscle, most of the 8-azido-cyclic [32P]AMP was incorporated into a protein band with an apparent molecular weight of 56,000 which shifted to 54,000 upon treatment with a phosphoprotein phosphatase. Thus a substantial amount of the cAMP-binding protein appeared to be in the phosphorylated form. Autoradiograms following sodium dodecyl sulfate-polyacrylamide gel electrophoresis of both the pure and impure cAMP-binding proteins labeled with 8-azido-cyclic [32P]AMP revealed another binding component with a molecular weight of 52,000 which incorporated 32P from [gamma-32P]ATP without changing its electrophoretic mobility. Limited proteolysis of the 56,000- and 52,000-dalton proteins labeled with 32P from either [gamma-32P]ATP.Mg2+ or 8-azido-cyclic [32P]AMP showed patterns indicating homology. On the other hand, peptide maps of the major 8-azido-cyclic [32P]AMP-labeled proteins from tissue extracts of bovine cardiac muscle (Mr = 56,000) and rabbit skeletal muscle (Mr = 48,000) displayed completely different patterns as expected for the cAMP-binding components of types II and I protein kinases. Both phospho- and dephospho-cAMP-binding components from the purified bovine cardiac muscle protein kinase were also resolved by isoelectric focusing on polyacrylamide slab gels containing 8 M urea. The phosphorylated forms labeled with 32P from either [gamma-32P]ATP or 8-azido-cyclic [32P]AMP migrated as a doublet with a pI of 5.35. The 8-azido-cyclic [32P]AMP-labeled dephosphorylated form also migrated as a doublet with a pI of 5.40. The phosphorylated and dephosphorylated cAMP-binding proteins migrated with molecular weights of 56,000 and 54,000, respectively, following a second dimension electrophoresis in sodium dodecyl sulfate. The lower molecular weight cAMP-binding component (Mr = 52,000) was also apparent in these gels. Similar experiments with the cAMP-binding proteins present in tissue extracts of bovine cardiac muscle indicate that they are predominantly in the phosphorylated form.", "contents": "Resolution of the phosphorylated and dephosphorylated cAMP-binding proteins of bovine cardiac muscle by affinity labeling and two-dimensional electrophoresis. The photoaffinity label 8-azido[32P]adenosine 3':5'-monophosphate (8-azido-cyclic [32P]AMP) was used to analyze both the cAMP-binding component of the purified cAMP-dependent protein kinase, and the cAMP-binding proteins present in crude tissue extracts of bovine cardiac muscle. 8-Azido-cyclic [32P]AMP reacted specifically and in stoichiometric amounts with the cAMP-binding proteins of bovine cardiac muscle. Upon phosphorylation, the purified cAMP-binding protein from bovine cardiac muscle changed its electrophoretic mobility on sodium dodecyl sulfate-polyacrylamide gels from an apparent molecular weight of 54,000 to an apparent molecular weight of 56,000. In tissue extracts of bovine cardiac muscle, most of the 8-azido-cyclic [32P]AMP was incorporated into a protein band with an apparent molecular weight of 56,000 which shifted to 54,000 upon treatment with a phosphoprotein phosphatase. Thus a substantial amount of the cAMP-binding protein appeared to be in the phosphorylated form. Autoradiograms following sodium dodecyl sulfate-polyacrylamide gel electrophoresis of both the pure and impure cAMP-binding proteins labeled with 8-azido-cyclic [32P]AMP revealed another binding component with a molecular weight of 52,000 which incorporated 32P from [gamma-32P]ATP without changing its electrophoretic mobility. Limited proteolysis of the 56,000- and 52,000-dalton proteins labeled with 32P from either [gamma-32P]ATP.Mg2+ or 8-azido-cyclic [32P]AMP showed patterns indicating homology. On the other hand, peptide maps of the major 8-azido-cyclic [32P]AMP-labeled proteins from tissue extracts of bovine cardiac muscle (Mr = 56,000) and rabbit skeletal muscle (Mr = 48,000) displayed completely different patterns as expected for the cAMP-binding components of types II and I protein kinases. Both phospho- and dephospho-cAMP-binding components from the purified bovine cardiac muscle protein kinase were also resolved by isoelectric focusing on polyacrylamide slab gels containing 8 M urea. The phosphorylated forms labeled with 32P from either [gamma-32P]ATP or 8-azido-cyclic [32P]AMP migrated as a doublet with a pI of 5.35. The 8-azido-cyclic [32P]AMP-labeled dephosphorylated form also migrated as a doublet with a pI of 5.40. The phosphorylated and dephosphorylated cAMP-binding proteins migrated with molecular weights of 56,000 and 54,000, respectively, following a second dimension electrophoresis in sodium dodecyl sulfate. The lower molecular weight cAMP-binding component (Mr = 52,000) was also apparent in these gels. Similar experiments with the cAMP-binding proteins present in tissue extracts of bovine cardiac muscle indicate that they are predominantly in the phosphorylated form."}
{"id": "PMID:218943", "title": "Quantitation of the various termini generated by type II restriction endonucleases using the polynucleotide kinase exchange reaction.", "content": "Parameters of the polynucleotide kinase-catalyzed exchange reaction between [gamma-32P]ATP and 5'-phosphoryl DNAs have been measured with the termini generated by the following endonucleases: EcoRI (Berkner, K. L., and Folk, W. R. (1977) J. Biol. Chem. 252, 3176-3184), Hpa II, BamHI, and HindIII (external termini); HindII and Hpa I (blunt terminal); Hae II and Hha I (internal termini). In every case, exchange is reproducible and proportional to the number of termini. However, in most cases, the exchange reaction does not proceed to the theoretical maximum. External termini and single-stranded DNAs are labeled more rapidly and to approximately 5-fold higher levels than blunt or internal termini. Concentrations of 100 to 200 microns ADP and 12 microns ATP are optimal for labeling all types of termini with the exchange reaction.", "contents": "Quantitation of the various termini generated by type II restriction endonucleases using the polynucleotide kinase exchange reaction. Parameters of the polynucleotide kinase-catalyzed exchange reaction between [gamma-32P]ATP and 5'-phosphoryl DNAs have been measured with the termini generated by the following endonucleases: EcoRI (Berkner, K. L., and Folk, W. R. (1977) J. Biol. Chem. 252, 3176-3184), Hpa II, BamHI, and HindIII (external termini); HindII and Hpa I (blunt terminal); Hae II and Hha I (internal termini). In every case, exchange is reproducible and proportional to the number of termini. However, in most cases, the exchange reaction does not proceed to the theoretical maximum. External termini and single-stranded DNAs are labeled more rapidly and to approximately 5-fold higher levels than blunt or internal termini. Concentrations of 100 to 200 microns ADP and 12 microns ATP are optimal for labeling all types of termini with the exchange reaction."}
{"id": "PMID:218944", "title": "The effect of beta-xylosides on heparan sulfate synthesis by SV40-transformed Swiss mouse 3T3 cells.", "content": "The medium and cell surface heparan sulfates isolated from SV40-transformed Swiss mouse 3T3 cells were examined in the presence and absence of 1.0 mM p-nitrophenyl-beta-D-xyloside. Incubation of the SV3T3 cells with this beta-xyloside resulted in: (a) a 4- to 5-fold reduction in the molecular weight distribution of medium heparan sulfate, (b) a 10-fold increase in the total synthesis of medium heparan sulfate, and (c) a small reduction in cell growth. There was little, if any, change in either the total level of synthesis or the molecular weight distribution of cell surface heparan sulfate. The covalent association of the beta-xyloside to the medium heparan sulfate was demonstrated by an analysis of the medium heparan sulfate produced by cells grown in the presence of [35S]sulfate and the fluorogenic beta-xyloside, 4-methylumbelliferyl-beta-D-xyloside. Treatment of the purified radiolabeled and fluorogenic heparan sulfate with either nitrous acid or heparitinase resulted in a decrease in the molecular weight of both radiolabeled and fluorogenic material. The data presented in this paper are discussed with respect to both the structure of heparan sulfate and the putative role of heparan sulfate in cell social behavior.", "contents": "The effect of beta-xylosides on heparan sulfate synthesis by SV40-transformed Swiss mouse 3T3 cells. The medium and cell surface heparan sulfates isolated from SV40-transformed Swiss mouse 3T3 cells were examined in the presence and absence of 1.0 mM p-nitrophenyl-beta-D-xyloside. Incubation of the SV3T3 cells with this beta-xyloside resulted in: (a) a 4- to 5-fold reduction in the molecular weight distribution of medium heparan sulfate, (b) a 10-fold increase in the total synthesis of medium heparan sulfate, and (c) a small reduction in cell growth. There was little, if any, change in either the total level of synthesis or the molecular weight distribution of cell surface heparan sulfate. The covalent association of the beta-xyloside to the medium heparan sulfate was demonstrated by an analysis of the medium heparan sulfate produced by cells grown in the presence of [35S]sulfate and the fluorogenic beta-xyloside, 4-methylumbelliferyl-beta-D-xyloside. Treatment of the purified radiolabeled and fluorogenic heparan sulfate with either nitrous acid or heparitinase resulted in a decrease in the molecular weight of both radiolabeled and fluorogenic material. The data presented in this paper are discussed with respect to both the structure of heparan sulfate and the putative role of heparan sulfate in cell social behavior."}
{"id": "PMID:218945", "title": "Spectral evidence for tyrosine ionization linked to a conformational change in liver alcohol dehydrogenase ternary complexes.", "content": "Resonance energy transfer from Trp-314 to ionized Tyr-286 was proposed (Laws, W. R., and Shore, J. D. (1978) J. Biol. Chem. 253, 8593-8597) as the mechanism for the observed decrease in protein fluorescence of liver alcohol dehydrogenase seen with alkaline pH, or with the formation of a ternary complex with NAD+ and trifluoroethanol. In the present study, ultraviolet difference spectra confirm the presence of ionized tyrosine not only in these two cases but also in the ternary complex with NADH and isobutyramide. Our results indicate that ternary complex formation, with either oxidized or reduced coenzyme, causes a conformational change leading to partial ionization of tyrosine residues in regions of the enzyme far from the active site.", "contents": "Spectral evidence for tyrosine ionization linked to a conformational change in liver alcohol dehydrogenase ternary complexes. Resonance energy transfer from Trp-314 to ionized Tyr-286 was proposed (Laws, W. R., and Shore, J. D. (1978) J. Biol. Chem. 253, 8593-8597) as the mechanism for the observed decrease in protein fluorescence of liver alcohol dehydrogenase seen with alkaline pH, or with the formation of a ternary complex with NAD+ and trifluoroethanol. In the present study, ultraviolet difference spectra confirm the presence of ionized tyrosine not only in these two cases but also in the ternary complex with NADH and isobutyramide. Our results indicate that ternary complex formation, with either oxidized or reduced coenzyme, causes a conformational change leading to partial ionization of tyrosine residues in regions of the enzyme far from the active site."}
{"id": "PMID:218946", "title": "Use of heme spin-labeling to probe heme environments of alpha and beta chains of hemoglobin.", "content": "A spin label attached to a propionic acid group of the heme has been used to probe the heme environment of the alpha and beta chains of hemoglobin in both the subunit and tetrameric forms. The electron paramagnetic resonance (EPR) studies of hemoglobin hybrids in which the spin label is attached to either the alpha- or beta-heme (alpha2SLbeta 2 or alpha2beta2SL) and spin-labeled isolated chains (alphaSL and betaSL) show that: 1) alpha- and beta-hemes have different environments in the tetrameric forms of oxy-, deoxy-, and methemoglobins as well as in isolated single chains; 2) when isolated subunits associate to form hemoglobin tetramers, the environment of the alpha-heme changes more drastically than that of the beta-heme; 3) upon deoxygenation of hemoglobin, the structure in the vicinity of the alpha-heme changes more drastically than that of the beta-heme; and 4) upon the addition of organic phosphates to methemoglobin, the change in the spin state of the heme irons mainly arises from beta-heme. The results demonstrate conclusively that the alpha and the beta subunits of hemoglobin are structurally nonequivalent as are their structural changes as the result of ligation. The relationship of EPR spectrum and structure of hemoglobin is discussed.", "contents": "Use of heme spin-labeling to probe heme environments of alpha and beta chains of hemoglobin. A spin label attached to a propionic acid group of the heme has been used to probe the heme environment of the alpha and beta chains of hemoglobin in both the subunit and tetrameric forms. The electron paramagnetic resonance (EPR) studies of hemoglobin hybrids in which the spin label is attached to either the alpha- or beta-heme (alpha2SLbeta 2 or alpha2beta2SL) and spin-labeled isolated chains (alphaSL and betaSL) show that: 1) alpha- and beta-hemes have different environments in the tetrameric forms of oxy-, deoxy-, and methemoglobins as well as in isolated single chains; 2) when isolated subunits associate to form hemoglobin tetramers, the environment of the alpha-heme changes more drastically than that of the beta-heme; 3) upon deoxygenation of hemoglobin, the structure in the vicinity of the alpha-heme changes more drastically than that of the beta-heme; and 4) upon the addition of organic phosphates to methemoglobin, the change in the spin state of the heme irons mainly arises from beta-heme. The results demonstrate conclusively that the alpha and the beta subunits of hemoglobin are structurally nonequivalent as are their structural changes as the result of ligation. The relationship of EPR spectrum and structure of hemoglobin is discussed."}
{"id": "PMID:218949", "title": "Phosphorylation of synthetic peptide analogs of rabbit cardiac troponin inhibitory subunit by the cyclic AMP-dependent protein kinase.", "content": "A series of synthetic peptide analogs of the cardiac troponin inhibitory subunit (TN-1) phosphorylation site sequence, Arg12-Pro-Ala-Pro-Ala-Val-Arg18-Arg19-Ser20-Asp21-Arg22-Ala, have been tested as substrates for the catalytic subunit of the cyclic AMP-dependent protein kinase (EC 2.7.1.37, ATP:protein phosphotransferase). As substrates, these peptides were generally inferior to the pyruvate kinase analog peptide Leu-Arg-Arg-Ala-Ser-Leu-Gly or its COOH-terminal amide analog. Replacing Arg-19 with alanine had only a minor effect on the kinetics of phosphorylation of the TN-1 peptide analog. In contrast, replacement of Arg-22 and Arg-18 with alanine resulted in marked enhancement and reduction of the Vmax, respectively. The results of this study have demonstrated that synthetic peptide analogs of the local phosphorylation site sequences of natural substrates may differ widely in their capacity to act as substrates for this protein kinase. In the case of the TN-1 peptide analogs, the contribution of the 4 arginine residues can be distinguished in terms of their influence on the kinetics of phosphorylation.", "contents": "Phosphorylation of synthetic peptide analogs of rabbit cardiac troponin inhibitory subunit by the cyclic AMP-dependent protein kinase. A series of synthetic peptide analogs of the cardiac troponin inhibitory subunit (TN-1) phosphorylation site sequence, Arg12-Pro-Ala-Pro-Ala-Val-Arg18-Arg19-Ser20-Asp21-Arg22-Ala, have been tested as substrates for the catalytic subunit of the cyclic AMP-dependent protein kinase (EC 2.7.1.37, ATP:protein phosphotransferase). As substrates, these peptides were generally inferior to the pyruvate kinase analog peptide Leu-Arg-Arg-Ala-Ser-Leu-Gly or its COOH-terminal amide analog. Replacing Arg-19 with alanine had only a minor effect on the kinetics of phosphorylation of the TN-1 peptide analog. In contrast, replacement of Arg-22 and Arg-18 with alanine resulted in marked enhancement and reduction of the Vmax, respectively. The results of this study have demonstrated that synthetic peptide analogs of the local phosphorylation site sequences of natural substrates may differ widely in their capacity to act as substrates for this protein kinase. In the case of the TN-1 peptide analogs, the contribution of the 4 arginine residues can be distinguished in terms of their influence on the kinetics of phosphorylation."}
{"id": "PMID:218952", "title": "Inhibition of erythrocyte membrane (Na+ + K+)-activated ATPase by ozone-treated phospholipids.", "content": "Ozone-treated aqueous suspensions of natural phospholipids yield at least two types of inhibitors of human erythrocyte membrane (Na+ + K+)-ATPase. The more labile ones appear to be carbonyl-containing substances whose inhibitory properties are enhanced if ozonolysis takes place in the presence of putrescine or glycine. Other amines of similar structure are much less effective as potentiators. Semicarbazide destroys the inhibitory properties of the more labile substances and can release putrescine from the complexes it forms with the carbonyl products of ozonolysis. 3the more stable inhibitors are unaffected by putrescine, glycine, or semicarbazide. Synthetic, saturated phospholipids do not produce these inhibitors during ozonolysis.", "contents": "Inhibition of erythrocyte membrane (Na+ + K+)-activated ATPase by ozone-treated phospholipids. Ozone-treated aqueous suspensions of natural phospholipids yield at least two types of inhibitors of human erythrocyte membrane (Na+ + K+)-ATPase. The more labile ones appear to be carbonyl-containing substances whose inhibitory properties are enhanced if ozonolysis takes place in the presence of putrescine or glycine. Other amines of similar structure are much less effective as potentiators. Semicarbazide destroys the inhibitory properties of the more labile substances and can release putrescine from the complexes it forms with the carbonyl products of ozonolysis. 3the more stable inhibitors are unaffected by putrescine, glycine, or semicarbazide. Synthetic, saturated phospholipids do not produce these inhibitors during ozonolysis."}
{"id": "PMID:218953", "title": "Biosynthesis of lipid-linked oligosaccharides. Isolation and structure of a second lipid-linked oligosaccharide in Chinese hamster ovary cells.", "content": "Previous work has shown that vesicular stomatitis virus-infected Chinese hamster ovary cells contain a major high molecular weight lipid-linked oligosaccharide which is transferred en bloc to protein during the formation of the asparagine-linked complex-type oligosaccharides of the vesicular stomatitis virus G protein (Tabas, I., Schlesinger, S., and Kornfeld, S. (1978) J. Biol. Chem. 253, 716-722). We now report the characterization of a second, lower molecular weight lipid-linked oligosaccharide. The oligosaccharide portion of this molecule was isolated and its structure was determined by methylation analysis, digestion with exoglycosidases, acetolysis and Smith periodate degradation to be: (formula: see text). Several lines of evidence are presented which indicate that this lipid-linked oligosaccharide is primarily involved in the assembly of the major lipid-linked oligosaccharide rather than in the direct glycosylation of proteins.", "contents": "Biosynthesis of lipid-linked oligosaccharides. Isolation and structure of a second lipid-linked oligosaccharide in Chinese hamster ovary cells. Previous work has shown that vesicular stomatitis virus-infected Chinese hamster ovary cells contain a major high molecular weight lipid-linked oligosaccharide which is transferred en bloc to protein during the formation of the asparagine-linked complex-type oligosaccharides of the vesicular stomatitis virus G protein (Tabas, I., Schlesinger, S., and Kornfeld, S. (1978) J. Biol. Chem. 253, 716-722). We now report the characterization of a second, lower molecular weight lipid-linked oligosaccharide. The oligosaccharide portion of this molecule was isolated and its structure was determined by methylation analysis, digestion with exoglycosidases, acetolysis and Smith periodate degradation to be: (formula: see text). Several lines of evidence are presented which indicate that this lipid-linked oligosaccharide is primarily involved in the assembly of the major lipid-linked oligosaccharide rather than in the direct glycosylation of proteins."}
{"id": "PMID:218958", "title": "Modulation of glucose uptake in animal cells. Studies using plasma membrane vesicles isolated from nontransformed and simian virus 40-transformed mouse fibroblast cultures.", "content": "Plasma membrane vesicles isolated from nontransformed and Simian virus 40-transformed mouse fibroblast cultures catalyzed carrier-mediated D-glucose transport without detectable metabolic conversion to glucose 6-phosphate. Glucose transport activity was stereospecific, temperature-dependent, sensitive to inactivation by p-chloromercuriphenylsulfonate, and accompanied plasma membrane material during subcellular fractionation. D-Glucose efflux from vesicles was inhibited by phloretin, an inhibitor of glucose uptake in intact cells. Cytochalasin B, a potent inhibitor of glucose uptake when tested with the intact cells used for vesicle isolation did not inhibit glucose transport in vesicles despite the presence of high affinity cytochalasin binding sites in isolated membranes. The enhanced glucose uptake observed in intact cells after viral transformation was not expressed in vesicles: no significant differences in glucose transport specific activity could be detected in vesicle preparations from nontransformed and transformed mouse fibroblast cultures. These findings indicate that cellular components distinct from glucose carriers can mediate changes in glucose uptake in mouse fibroblast cultures in at least two cases: sensitivity to inhibition by cytochalasin B and the enhanced cellular sugar uptake observed after viral transformation.", "contents": "Modulation of glucose uptake in animal cells. Studies using plasma membrane vesicles isolated from nontransformed and simian virus 40-transformed mouse fibroblast cultures. Plasma membrane vesicles isolated from nontransformed and Simian virus 40-transformed mouse fibroblast cultures catalyzed carrier-mediated D-glucose transport without detectable metabolic conversion to glucose 6-phosphate. Glucose transport activity was stereospecific, temperature-dependent, sensitive to inactivation by p-chloromercuriphenylsulfonate, and accompanied plasma membrane material during subcellular fractionation. D-Glucose efflux from vesicles was inhibited by phloretin, an inhibitor of glucose uptake in intact cells. Cytochalasin B, a potent inhibitor of glucose uptake when tested with the intact cells used for vesicle isolation did not inhibit glucose transport in vesicles despite the presence of high affinity cytochalasin binding sites in isolated membranes. The enhanced glucose uptake observed in intact cells after viral transformation was not expressed in vesicles: no significant differences in glucose transport specific activity could be detected in vesicle preparations from nontransformed and transformed mouse fibroblast cultures. These findings indicate that cellular components distinct from glucose carriers can mediate changes in glucose uptake in mouse fibroblast cultures in at least two cases: sensitivity to inhibition by cytochalasin B and the enhanced cellular sugar uptake observed after viral transformation."}
{"id": "PMID:218960", "title": "ADP ribosylation of rat liver lysine-rich histone in vitro.", "content": "Purified rat liver nuclei were incubated with [14C]-NAD+ and the various nuclear protein fractions were separated. Forty per cent of the total radioactivity incorporated was associated with the histone fraction. Of this, about 50% was extracted with H1, in 0.5 N perchloric acid. When crude H1 was purified and fractionated into five different subfractions by chromatography on Bio-Rex 70, it was found that all the H1 subfractions contained radioactivity. This radioactive material was identified as oligomers of adenosine diphosphate ribose (ADP-Rib) with an average chain length which corresponded to trimers. The extent of the modification was dependent on the concentration of NAD+. About 60% of the H1 molecules were modified with a concentration of 1 mM NAD+. The presence of these oligomers of ADP-Rib introduced a large degree of microheterogeneity to H1 as detected by electrophoresis in polyacrylamide gels containing 2.5 M urea and 0.9 N acetic acid. Bands of H1 with 10 to 20% less mobility than the unmodified H1 were present. Also, as a consequence of large content of ADP-Rib, the absorption maximum shifted from 275 to 259 nm. The half-life of the bond between the oligomers of ADP-Rib and H1 was about 3 min at 37 degrees C in the presence of 0.1 N NaOH, and 10 m1 were modified. The site of ADP ribosylation in the NH2-terminal half was localized in the tryptic peptide extending from the NH2-terminal end to lysine 15. The site of modification of the COOH-erminal half was localized in the tryptic peptide which contained the only glutamic acid residue in this fragment of H1...", "contents": "ADP ribosylation of rat liver lysine-rich histone in vitro. Purified rat liver nuclei were incubated with [14C]-NAD+ and the various nuclear protein fractions were separated. Forty per cent of the total radioactivity incorporated was associated with the histone fraction. Of this, about 50% was extracted with H1, in 0.5 N perchloric acid. When crude H1 was purified and fractionated into five different subfractions by chromatography on Bio-Rex 70, it was found that all the H1 subfractions contained radioactivity. This radioactive material was identified as oligomers of adenosine diphosphate ribose (ADP-Rib) with an average chain length which corresponded to trimers. The extent of the modification was dependent on the concentration of NAD+. About 60% of the H1 molecules were modified with a concentration of 1 mM NAD+. The presence of these oligomers of ADP-Rib introduced a large degree of microheterogeneity to H1 as detected by electrophoresis in polyacrylamide gels containing 2.5 M urea and 0.9 N acetic acid. Bands of H1 with 10 to 20% less mobility than the unmodified H1 were present. Also, as a consequence of large content of ADP-Rib, the absorption maximum shifted from 275 to 259 nm. The half-life of the bond between the oligomers of ADP-Rib and H1 was about 3 min at 37 degrees C in the presence of 0.1 N NaOH, and 10 m1 were modified. The site of ADP ribosylation in the NH2-terminal half was localized in the tryptic peptide extending from the NH2-terminal end to lysine 15. The site of modification of the COOH-erminal half was localized in the tryptic peptide which contained the only glutamic acid residue in this fragment of H1..."}
{"id": "PMID:218961", "title": "Inhibitor of human collagenase from cultures of human tendon.", "content": "A potent inhibitor of human collagenases, released from human tendon explants in culture, has been purified and partially characterized. The tendon inhibitor has an estimated molecular weight of 25,000. It is relatively heat-stable but undergoes loss of activity following exposure to trypsin. It inhibits trypsin-activated rheumatoid synovial collagenase as well as the enzyme obtained from polymorphonuclear leukocytes. No inhibition of collagenase from Clostridium histolyticum (clostridiopeptidase A, EC 3.4.24.3) was noted. This collagenase inhibitor may be a factor in the regulation of extracellular connective tissue catabolism.", "contents": "Inhibitor of human collagenase from cultures of human tendon. A potent inhibitor of human collagenases, released from human tendon explants in culture, has been purified and partially characterized. The tendon inhibitor has an estimated molecular weight of 25,000. It is relatively heat-stable but undergoes loss of activity following exposure to trypsin. It inhibits trypsin-activated rheumatoid synovial collagenase as well as the enzyme obtained from polymorphonuclear leukocytes. No inhibition of collagenase from Clostridium histolyticum (clostridiopeptidase A, EC 3.4.24.3) was noted. This collagenase inhibitor may be a factor in the regulation of extracellular connective tissue catabolism."}
{"id": "PMID:218962", "title": "Single strand DNA binding of simian virus 40 tumor antigen.", "content": "Simian virus 40 T antigen binds to both single and double strand DNA. The single and double strand DNA binding activity of crude T antigen preparations was evaluated by chromatography of the antigen on DNA-cellulose columns. Crude T antigen was retained on both native and denatured DNA-cellulos columns and was eluted from both columns under similar conditions. The interaction of highly purified T antigen with single and double strand DNA was evaluated by competition experiments using a DNA filter binding assay. These experiments showed that T antigen binds preferentially to single strand calf thymus DNA by more than an order of magnitude when compared to double strand calf thymus DNA.", "contents": "Single strand DNA binding of simian virus 40 tumor antigen. Simian virus 40 T antigen binds to both single and double strand DNA. The single and double strand DNA binding activity of crude T antigen preparations was evaluated by chromatography of the antigen on DNA-cellulose columns. Crude T antigen was retained on both native and denatured DNA-cellulos columns and was eluted from both columns under similar conditions. The interaction of highly purified T antigen with single and double strand DNA was evaluated by competition experiments using a DNA filter binding assay. These experiments showed that T antigen binds preferentially to single strand calf thymus DNA by more than an order of magnitude when compared to double strand calf thymus DNA."}
{"id": "PMID:218964", "title": "In vitro synthesis of a putative precursor to the mitochondrial enzyme, carbamyl phosphate synthetase.", "content": "A simple and rapid procedure is described for purification of carbamyl phosphate synthetase from the matrix fraction of rat liver mitochondria. Antibodies to the enzyme were raised in sheep and purified from antiserum by affinity chromatography on enzyme-bound Sepharose columns. When membrane-free polyribosomes, isolated from a cytosolic fraction of rat liver, were incubated in a messenger-dependent rabbit reticulocyte protein-synthesizing system in the presence of [35S]methionine, the purified antibody precipitated a product of translation representing 0.2% of total trichloroacetic acid-insoluble radioactivity. It demonstrated mobility characteristics in sodium dodecyl sulfate-polyacrylamide gels expected for a polypeptide of molecular mass approximately 5500 daltons larger than the mature mitochondrial form of the enzyme (160,000 daltons). Proteolysis of both the mature and presumptive in vitro precursor forms of the enzyme yielded respective sets of peptide fragments which gave similar patterns upon gel electrophoresis. Excess mitochondrial enzyme effectively competed with the in vitro product for interaction with anti-carbamyl phosphate synthetase antibody.", "contents": "In vitro synthesis of a putative precursor to the mitochondrial enzyme, carbamyl phosphate synthetase. A simple and rapid procedure is described for purification of carbamyl phosphate synthetase from the matrix fraction of rat liver mitochondria. Antibodies to the enzyme were raised in sheep and purified from antiserum by affinity chromatography on enzyme-bound Sepharose columns. When membrane-free polyribosomes, isolated from a cytosolic fraction of rat liver, were incubated in a messenger-dependent rabbit reticulocyte protein-synthesizing system in the presence of [35S]methionine, the purified antibody precipitated a product of translation representing 0.2% of total trichloroacetic acid-insoluble radioactivity. It demonstrated mobility characteristics in sodium dodecyl sulfate-polyacrylamide gels expected for a polypeptide of molecular mass approximately 5500 daltons larger than the mature mitochondrial form of the enzyme (160,000 daltons). Proteolysis of both the mature and presumptive in vitro precursor forms of the enzyme yielded respective sets of peptide fragments which gave similar patterns upon gel electrophoresis. Excess mitochondrial enzyme effectively competed with the in vitro product for interaction with anti-carbamyl phosphate synthetase antibody."}
{"id": "PMID:218965", "title": "No effect of cAMP on protein synthesis in reticulocyte lysates.", "content": "The results of a series of experiments are interpreted to indicate that protein synthesis in reticulocyte lysates is not affected by the reticulocyte cAMP-dependent protein kinase. The catalytic subunit of this enzyme was isolated to apparent homogeneity. Also, the protein inhibitor of this protein kinase was isolated from muscle. Neither physiological concentrations of cAMP nor any of these protein components had a detectable effect on protein synthesis in reticulocyte lysates in the presence or absence of exogenous heme. Phosphorylation of the smallest subunit of eukaryotic initiation factor 2 or the 90,000 to 100,000-dalton peptide associated with eukaryotic initiation factor 2 kinase activity were not affected by the activity of the cAMP-dependent protein kinase under conditions in which exogenous heme has a pronounced effect on these reactions.", "contents": "No effect of cAMP on protein synthesis in reticulocyte lysates. The results of a series of experiments are interpreted to indicate that protein synthesis in reticulocyte lysates is not affected by the reticulocyte cAMP-dependent protein kinase. The catalytic subunit of this enzyme was isolated to apparent homogeneity. Also, the protein inhibitor of this protein kinase was isolated from muscle. Neither physiological concentrations of cAMP nor any of these protein components had a detectable effect on protein synthesis in reticulocyte lysates in the presence or absence of exogenous heme. Phosphorylation of the smallest subunit of eukaryotic initiation factor 2 or the 90,000 to 100,000-dalton peptide associated with eukaryotic initiation factor 2 kinase activity were not affected by the activity of the cAMP-dependent protein kinase under conditions in which exogenous heme has a pronounced effect on these reactions."}
{"id": "PMID:218966", "title": "Identification of histidine-119 as the target in the site-specific inactivation of ribonuclease A by ferrate ion.", "content": "Ferrate ion, a powerful oxidant which is an analog of orthophosphate ion, has previously shown some promise as a site-specific probe of enzymes which interact with phosphate compounds. In order to explore the general applicability of this reagent, it has been tested against ribonuclease A, an enzyme whose structure and active center have been well described. Treatment with a molar ratio of ferrate to enzyme of less than 20 leads to a loss of 87% of the activity. The known competitive inhibitors, 2'-cytidylic acid, inorganic pyrophosphate, and orthophosphate all protect the enzyme from inactivation. Inactivation is accompanied by a loss of the capacity to bind 2'-cytidylic acid. Ferrate inactivation at pH 5.0 is accompanied by the modification of only one amino acid. The amino acid which was identified by amino acid and sequence analyses of peptide fragments obtained by cyanogen bromide treatment and selective proteolysis proved to be histidine-119, whose essential role at the active center has long been established.", "contents": "Identification of histidine-119 as the target in the site-specific inactivation of ribonuclease A by ferrate ion. Ferrate ion, a powerful oxidant which is an analog of orthophosphate ion, has previously shown some promise as a site-specific probe of enzymes which interact with phosphate compounds. In order to explore the general applicability of this reagent, it has been tested against ribonuclease A, an enzyme whose structure and active center have been well described. Treatment with a molar ratio of ferrate to enzyme of less than 20 leads to a loss of 87% of the activity. The known competitive inhibitors, 2'-cytidylic acid, inorganic pyrophosphate, and orthophosphate all protect the enzyme from inactivation. Inactivation is accompanied by a loss of the capacity to bind 2'-cytidylic acid. Ferrate inactivation at pH 5.0 is accompanied by the modification of only one amino acid. The amino acid which was identified by amino acid and sequence analyses of peptide fragments obtained by cyanogen bromide treatment and selective proteolysis proved to be histidine-119, whose essential role at the active center has long been established."}
{"id": "PMID:218969", "title": "Structural differences between apo- and holoenzyme of horse liver alcohol dehydrogenase.", "content": "The three-dimensional structure of a ternary complex of horse liver alcohol dehydrogenase with reduced nicotinamide adenine dinucleotide and the inhibitor dimethyl sulfoxide has been determined to 4.5 A resolution independently of the apoenzyme structure. The electron density maps of both structures have been compared. The two coenzyme binding domains which form the center of the dimer molecular have retained their conformation and orientation within the molecule whereas the catalytic domains rotate and narrow the cleft between the domains. The active site becomes shielded from the solution by a combination of this rotation, local movements of a loop from residues 53 to 57 and coenzyme and substrate binding. Both subunits bind coenzyme and inhibitor to the same extent. The nicotinamide ring of the coenzyme is positioned close to the active zinc atom and the inhibitor is bound to this zinc atom. The difference between the two crystallographically independent subunits is small. The proposed mechanisms of action for the enzyme based on the apoenzyme structure are confirmed by the present investigation.", "contents": "Structural differences between apo- and holoenzyme of horse liver alcohol dehydrogenase. The three-dimensional structure of a ternary complex of horse liver alcohol dehydrogenase with reduced nicotinamide adenine dinucleotide and the inhibitor dimethyl sulfoxide has been determined to 4.5 A resolution independently of the apoenzyme structure. The electron density maps of both structures have been compared. The two coenzyme binding domains which form the center of the dimer molecular have retained their conformation and orientation within the molecule whereas the catalytic domains rotate and narrow the cleft between the domains. The active site becomes shielded from the solution by a combination of this rotation, local movements of a loop from residues 53 to 57 and coenzyme and substrate binding. Both subunits bind coenzyme and inhibitor to the same extent. The nicotinamide ring of the coenzyme is positioned close to the active zinc atom and the inhibitor is bound to this zinc atom. The difference between the two crystallographically independent subunits is small. The proposed mechanisms of action for the enzyme based on the apoenzyme structure are confirmed by the present investigation."}
{"id": "PMID:218970", "title": "25-Azavitamin D3, an inhibitor of vitamin D metabolism and action.", "content": "25-Azavitamin D3 inhibited both the bone calcium mobilization and intestinal calcium transport responses of rats to vitamin D3 but not to 25-hydroxyvitamin D3. Although 25-azavitamin D3 had no effect on the response of bone to 1alpha,25-dihydroxyvitamin D3, it did diminish the response of the intestine to that metabolite. 25-Azavitamin D3 increased liver vitamin D content and reduced the concentration of 25-hydroxyvitamin D3 required to inhibit the metabolism of vitamin D3 (75 and 200 microgram) were similar to the doses of 25-azavitamin D3 required to inhibit the action of vitamin D3 in vivo (50 and 150 microgram). 25-Azavitamin D3 is thus a vitamin D antagonist, acting for the most part via inhibition of the liver 25-hydroxylation of vitamin D3.", "contents": "25-Azavitamin D3, an inhibitor of vitamin D metabolism and action. 25-Azavitamin D3 inhibited both the bone calcium mobilization and intestinal calcium transport responses of rats to vitamin D3 but not to 25-hydroxyvitamin D3. Although 25-azavitamin D3 had no effect on the response of bone to 1alpha,25-dihydroxyvitamin D3, it did diminish the response of the intestine to that metabolite. 25-Azavitamin D3 increased liver vitamin D content and reduced the concentration of 25-hydroxyvitamin D3 required to inhibit the metabolism of vitamin D3 (75 and 200 microgram) were similar to the doses of 25-azavitamin D3 required to inhibit the action of vitamin D3 in vivo (50 and 150 microgram). 25-Azavitamin D3 is thus a vitamin D antagonist, acting for the most part via inhibition of the liver 25-hydroxylation of vitamin D3."}
{"id": "PMID:218972", "title": "Lifetimes and NADH quenching of tryptophan fluorescence in pig heart cytoplasmic malate dehydrogenase.", "content": "The time-resolved and steady state fluorescence properties were measured for pig heart cytoplasmic malate dehydrogenase at pH 6.0 and 8.0. The fluorescence decay can be described by two rate processes, according to the functions: I(t) = 0.7e(-t/1.0) + 0.3e(-t/4.4) for the free enzyme and I(t) = 0.7e(-t/0.8) + 0.3e(-t/2.0 for the enzyme . NADH complex. Quenching by NADH of the tryptophan fluorescence is linear. The only effect of pH is to change the association constant for NADH binding; the fluorescence of the free enzyme and the fluorescence quenching by NADH, I-, and acrylamide are unaffected by pH. Thus there are no changes in conformation of the free enzyme or of the NADH complex over the range of pH 6 to 8.", "contents": "Lifetimes and NADH quenching of tryptophan fluorescence in pig heart cytoplasmic malate dehydrogenase. The time-resolved and steady state fluorescence properties were measured for pig heart cytoplasmic malate dehydrogenase at pH 6.0 and 8.0. The fluorescence decay can be described by two rate processes, according to the functions: I(t) = 0.7e(-t/1.0) + 0.3e(-t/4.4) for the free enzyme and I(t) = 0.7e(-t/0.8) + 0.3e(-t/2.0 for the enzyme . NADH complex. Quenching by NADH of the tryptophan fluorescence is linear. The only effect of pH is to change the association constant for NADH binding; the fluorescence of the free enzyme and the fluorescence quenching by NADH, I-, and acrylamide are unaffected by pH. Thus there are no changes in conformation of the free enzyme or of the NADH complex over the range of pH 6 to 8."}
{"id": "PMID:218974", "title": "Structure of simian virus 40 recombinants that contain both host and viral DNA sequences. I. The structure of variant CVPS/1/P2 (EcoRI res).", "content": "The entire nucleotide sequence (1210-base-pair repeating units) of a defective variant of simian virus 40 is presented. Within this variant there are deletions of large portions of the wild type genome and an inversion within the remaining wild type viral sequences. In addition, the defective variant contains DNA sequences derived from the permissive monkey cells in which the virus was propagated. The monkey sequences include a portion that is homologous to sequences within highly repeated monkey DNA (alpha component) as well as portions derived from sequences that are infrequently repeated in the monkey genome. One out of every three to four of the tandem 1210-base-pair repeat units contains in addition, a duplication of a part of the monkey sequences. The sequence information defines the structures of a number of recombinational joints which result from deletions, inversions, duplications, and insertions of host sequences into the viral genome. The data demonstrate that the various recombinational events that resulted in the formation of this defective variant did not depend on extensive homology between recombining segments.", "contents": "Structure of simian virus 40 recombinants that contain both host and viral DNA sequences. I. The structure of variant CVPS/1/P2 (EcoRI res). The entire nucleotide sequence (1210-base-pair repeating units) of a defective variant of simian virus 40 is presented. Within this variant there are deletions of large portions of the wild type genome and an inversion within the remaining wild type viral sequences. In addition, the defective variant contains DNA sequences derived from the permissive monkey cells in which the virus was propagated. The monkey sequences include a portion that is homologous to sequences within highly repeated monkey DNA (alpha component) as well as portions derived from sequences that are infrequently repeated in the monkey genome. One out of every three to four of the tandem 1210-base-pair repeat units contains in addition, a duplication of a part of the monkey sequences. The sequence information defines the structures of a number of recombinational joints which result from deletions, inversions, duplications, and insertions of host sequences into the viral genome. The data demonstrate that the various recombinational events that resulted in the formation of this defective variant did not depend on extensive homology between recombining segments."}
{"id": "PMID:218975", "title": "Structure of simian virus 40 recombinants that contain both host and viral DNA sequences. II. The structure of variant 1103 and its comparison to variant CVPS/1P2 (EcoRI res).", "content": "In an effort to characterize sites of recombination between SV40 and monkey DNA, we have determined the primary sequence of a large portion of the SV40 variant, designated 1103. This virus contains DNA sequences derived both from the wild type SV40 genome and from the permissive monkey cell in which the virus was propagated. Further, the monkey sequences included in the defective genome are homologous to both highly repeated monkey DNA (alpha component) and sequences that are infrequently repeated in the monkey genome. The regions of the 1103 genome where DNA sequences were determined include 1) the segments of the variant that surround joints connecting SV40 and monkey sequences, 2) the segment that contains the joint between monkey sequences of high and low reiteration frequency, and 3) the DNA segment of the variant that is homologous to monkey alpha component DNA. Comparison of the data obtained from the sequences analysis of the SV40 variants 1103 and CVP8/1/P2 (EcoRI res) (described in Wakamiya, T., McCutchan, T., Rosenberg, M., and Singer, M. (1979) J. Biol. Chem 254, 3584-3591) reveals certain similarities between the two that may be involved in eukaryotic recombination and defective variant formation.", "contents": "Structure of simian virus 40 recombinants that contain both host and viral DNA sequences. II. The structure of variant 1103 and its comparison to variant CVPS/1P2 (EcoRI res). In an effort to characterize sites of recombination between SV40 and monkey DNA, we have determined the primary sequence of a large portion of the SV40 variant, designated 1103. This virus contains DNA sequences derived both from the wild type SV40 genome and from the permissive monkey cell in which the virus was propagated. Further, the monkey sequences included in the defective genome are homologous to both highly repeated monkey DNA (alpha component) and sequences that are infrequently repeated in the monkey genome. The regions of the 1103 genome where DNA sequences were determined include 1) the segments of the variant that surround joints connecting SV40 and monkey sequences, 2) the segment that contains the joint between monkey sequences of high and low reiteration frequency, and 3) the DNA segment of the variant that is homologous to monkey alpha component DNA. Comparison of the data obtained from the sequences analysis of the SV40 variants 1103 and CVP8/1/P2 (EcoRI res) (described in Wakamiya, T., McCutchan, T., Rosenberg, M., and Singer, M. (1979) J. Biol. Chem 254, 3584-3591) reveals certain similarities between the two that may be involved in eukaryotic recombination and defective variant formation."}
{"id": "PMID:218977", "title": "Purification and characterization of poly(ADP-ribose) synthetase from calf thymus.", "content": "Poly(ADP-ribose) synthetase from calf thymus has been purified to apparent homogeneity by a simple and rapid method with a recovery of 10 to 20%. The enzyme activity absolutely requires the presence of DNA. Histone further stimulates the reaction. The Km for NAD and the maximal velocity at 25 degrees C and pH 8.0 in the presence of both compounds are 55 micron and 1,400 nmol/min/mg, respectively. The sedimentation coefficient (s020,w) of the enzyme is 5.80 S. The molecular weight is calculated to be 108,000 by sedimentation equilibrium method using a partial specific volume of 0.736 ml/g. This value is in good agreement with the molecular weight values of 115,000 and 120,000 determined by gel filtration on Sephadex G-200 and gel electrophoresis in the presence of sodium dodecyl sulfate, respectively. The enzyme is colorless and its absorption spectrum shows a maximum at 280 nm. From a CD spectrum, alpha helical content is estimated to be approximately 30%. The enzyme is a basic protein having a pI value of 9.8 and is rich in lysine rather than arginine. Neutral sugar, phospholipid, and DNA are not detected in the final preparation. These data indicate that the purified enzyme is a simple globular protein composed of a single polypeptide having an approximate molecular weight of 110,000.", "contents": "Purification and characterization of poly(ADP-ribose) synthetase from calf thymus. Poly(ADP-ribose) synthetase from calf thymus has been purified to apparent homogeneity by a simple and rapid method with a recovery of 10 to 20%. The enzyme activity absolutely requires the presence of DNA. Histone further stimulates the reaction. The Km for NAD and the maximal velocity at 25 degrees C and pH 8.0 in the presence of both compounds are 55 micron and 1,400 nmol/min/mg, respectively. The sedimentation coefficient (s020,w) of the enzyme is 5.80 S. The molecular weight is calculated to be 108,000 by sedimentation equilibrium method using a partial specific volume of 0.736 ml/g. This value is in good agreement with the molecular weight values of 115,000 and 120,000 determined by gel filtration on Sephadex G-200 and gel electrophoresis in the presence of sodium dodecyl sulfate, respectively. The enzyme is colorless and its absorption spectrum shows a maximum at 280 nm. From a CD spectrum, alpha helical content is estimated to be approximately 30%. The enzyme is a basic protein having a pI value of 9.8 and is rich in lysine rather than arginine. Neutral sugar, phospholipid, and DNA are not detected in the final preparation. These data indicate that the purified enzyme is a simple globular protein composed of a single polypeptide having an approximate molecular weight of 110,000."}
{"id": "PMID:218979", "title": "Alveolar cell carcinoma on CT scanning. The value of the air bronchogram sign.", "content": "The computed tomography findings in alveolar disease are described in a patient with alveolar cell carcinoma. The recognition of an air bronchogram on CT scanning may be useful in establishing the alveolar nature of diffuse or focal lung disease.", "contents": "Alveolar cell carcinoma on CT scanning. The value of the air bronchogram sign. The computed tomography findings in alveolar disease are described in a patient with alveolar cell carcinoma. The recognition of an air bronchogram on CT scanning may be useful in establishing the alveolar nature of diffuse or focal lung disease."}
{"id": "PMID:218980", "title": "An analysis of Con A-mediated agglutination in a Chinese hamster ovary subclone which responds morphologically to growth in dibutyryl cyclic AMP. III. The role of microvilli in the agglutination process.", "content": "We have used the H-7w subclone of a Chinese hamster ovary cell line (K1) to investigate the role of cell surface architecture (specifically microvilli, blebs, and sheets) in determining the relative agglutinability of a cell line with Con A. Our evidence clearly demonstrates that no specific, immediately recognizable surface architecture is associated with the agglutinable or non-agglutinable phenotype. Our data suggest that the expression of microvilli on the cell surface is neither necessary to nor sufficient for the phenotype described by enhanced agglutinability with Con A. Furthermore our work demonstrates that cells covered with blebs are as agglutinable as cells covered with microvilli thereby suggesting that the intertwining of microvilli may not be an essential facet of the agglutination phenomenon.", "contents": "An analysis of Con A-mediated agglutination in a Chinese hamster ovary subclone which responds morphologically to growth in dibutyryl cyclic AMP. III. The role of microvilli in the agglutination process. We have used the H-7w subclone of a Chinese hamster ovary cell line (K1) to investigate the role of cell surface architecture (specifically microvilli, blebs, and sheets) in determining the relative agglutinability of a cell line with Con A. Our evidence clearly demonstrates that no specific, immediately recognizable surface architecture is associated with the agglutinable or non-agglutinable phenotype. Our data suggest that the expression of microvilli on the cell surface is neither necessary to nor sufficient for the phenotype described by enhanced agglutinability with Con A. Furthermore our work demonstrates that cells covered with blebs are as agglutinable as cells covered with microvilli thereby suggesting that the intertwining of microvilli may not be an essential facet of the agglutination phenomenon."}
{"id": "PMID:218981", "title": "The pattern of appearance of enzymic activity during the development of the Golgi apparatus in amoebae.", "content": "The appearance of enzymic activity during the development of the Golgi apparatus was studied by cytochemical staining of renucleated amoebae. In cells enucleated for 4 days, there was a great decline in size and number of Golgi bodies, or dictyosomes. Subsequent renucleation by nuclear transplantation resulted in a regeneration of Golgi bodies. Samples of amoebae were fixed and incubated for cytochemical staining at intervals of 1, 6, or 24 h after renucleation. Enzymes selected for study were guanosine diphosphatase (GDPase), esterase, and thiamine pyrophosphatase (TPPase). All three were found in the Golgi apparatus of normal amoebae but they differed in their overall intracellular distribution. GDPase was normally present at the convex pole of the Golgi apparatus, in rough endoplasmic reticulum, and in the nuclear envelope. In amoebae renucleated for 1 h, light reaction product for GDPase was present throughout the small stacks of cisternae that represented the forming Golgi apparatus. By 6 h following the operation GDPase reaction product was concentrated at the convex pole of the Golgi apparatus. Esterase, which was distributed throughout the stacks of normal Golgi cisternae, displayed a similar distribution in the forming Golgi bodies as soon as they were visible. TPPase was normally present in the Golgi apparatus but was not found in the endoplasmic reticulum. In contrast to the other enzymes, TPPase reaction product was absent from the forming Golgi apparatus 1 and 6 h after renucleation, and did not appear in the Golgi apparatus until 24 h after operation. Thus, enzymes held in common between the rough endoplasmic reticulum and the Golgi apparatus were present in the forming Golgi apparatus as soon as it was detectable, but an enzyme cytochemically localized to the Golgi apparatus only appeared later in development of the organelle. It is suggested that Golgi membranes might be derived from the endoplasmic reticulum and thus immediately contain endoplasmic reticulum enzymes, while Golgi-specific enzymes are added later in development.", "contents": "The pattern of appearance of enzymic activity during the development of the Golgi apparatus in amoebae. The appearance of enzymic activity during the development of the Golgi apparatus was studied by cytochemical staining of renucleated amoebae. In cells enucleated for 4 days, there was a great decline in size and number of Golgi bodies, or dictyosomes. Subsequent renucleation by nuclear transplantation resulted in a regeneration of Golgi bodies. Samples of amoebae were fixed and incubated for cytochemical staining at intervals of 1, 6, or 24 h after renucleation. Enzymes selected for study were guanosine diphosphatase (GDPase), esterase, and thiamine pyrophosphatase (TPPase). All three were found in the Golgi apparatus of normal amoebae but they differed in their overall intracellular distribution. GDPase was normally present at the convex pole of the Golgi apparatus, in rough endoplasmic reticulum, and in the nuclear envelope. In amoebae renucleated for 1 h, light reaction product for GDPase was present throughout the small stacks of cisternae that represented the forming Golgi apparatus. By 6 h following the operation GDPase reaction product was concentrated at the convex pole of the Golgi apparatus. Esterase, which was distributed throughout the stacks of normal Golgi cisternae, displayed a similar distribution in the forming Golgi bodies as soon as they were visible. TPPase was normally present in the Golgi apparatus but was not found in the endoplasmic reticulum. In contrast to the other enzymes, TPPase reaction product was absent from the forming Golgi apparatus 1 and 6 h after renucleation, and did not appear in the Golgi apparatus until 24 h after operation. Thus, enzymes held in common between the rough endoplasmic reticulum and the Golgi apparatus were present in the forming Golgi apparatus as soon as it was detectable, but an enzyme cytochemically localized to the Golgi apparatus only appeared later in development of the organelle. It is suggested that Golgi membranes might be derived from the endoplasmic reticulum and thus immediately contain endoplasmic reticulum enzymes, while Golgi-specific enzymes are added later in development."}
{"id": "PMID:218983", "title": "Pseudohypoaldosteronism: multiple target organ unresponsiveness to mineralocorticoid hormones.", "content": "The first report of a 7-month-old male with pseudohypoaldosteronism in which unresponsiveness to mineralocorticoids has been demonstrated in the kidney, colon, and sweat and salivary glands is presented here. This is documented by urinary, salivary, and sweat sodium wasting in the presence of elevated urinary aldosterone excretion, plasma aldosterone concentration, and PRA. There was no mineralocorticoid response in the kidney or salivary or sweat glands to the administration of high doses of 9 alpha-flurocortisol. Furthermore, in this patient, the colonic mucosal cells failed to respond to exogenous aldosterone administration. Repeat evaluation at 25 months of age showed persistence of the sodium wasting and multiple target organ insensitivity to administered mineralocorticoid. Since this patient has defective mineralocorticoid response in the major sodium-conserving organs, the only therapy possible was administration of sodium to compensate for total sodium loss.", "contents": "Pseudohypoaldosteronism: multiple target organ unresponsiveness to mineralocorticoid hormones. The first report of a 7-month-old male with pseudohypoaldosteronism in which unresponsiveness to mineralocorticoids has been demonstrated in the kidney, colon, and sweat and salivary glands is presented here. This is documented by urinary, salivary, and sweat sodium wasting in the presence of elevated urinary aldosterone excretion, plasma aldosterone concentration, and PRA. There was no mineralocorticoid response in the kidney or salivary or sweat glands to the administration of high doses of 9 alpha-flurocortisol. Furthermore, in this patient, the colonic mucosal cells failed to respond to exogenous aldosterone administration. Repeat evaluation at 25 months of age showed persistence of the sodium wasting and multiple target organ insensitivity to administered mineralocorticoid. Since this patient has defective mineralocorticoid response in the major sodium-conserving organs, the only therapy possible was administration of sodium to compensate for total sodium loss."}
{"id": "PMID:218985", "title": "Immunoreactive somatomedin A in human serum.", "content": "A RIA has been developed for somatomedin A (SM-A) utilizing Sepharose-bound antibodies. This assay, measuring SM-A, the insulin-like growth factors 1 and 2, and somatomedin C, allows determination in serum samples. In comparison with a serum standard, the mean serum levels in patients with acromegaly or GH deficiency and healthy subjects were 8.7 %/- 0.7 (n = 25), 0.24 +/- 0.02 (n = 25), and 1.15 +/- 0.11 U/ml, respectively. The correlation coefficient between immunoreactive SM-A and SM-A by radioreceptor assay was highly significant (r = 0.93), although the potency ratio of SM-A between the two groups of patients was higher in the RIA than in the radioreceptor assay. Gel chromatography revealed that SM-A in acromegalic serum is bound to a carrier protein which is absent in patients with GH deficiency. After gel chromatography at low pH, 90% of applied immunoreactive SM-A was recovered in the low molecular weight fraction and consisted mainly of neutral polypeptides.", "contents": "Immunoreactive somatomedin A in human serum. A RIA has been developed for somatomedin A (SM-A) utilizing Sepharose-bound antibodies. This assay, measuring SM-A, the insulin-like growth factors 1 and 2, and somatomedin C, allows determination in serum samples. In comparison with a serum standard, the mean serum levels in patients with acromegaly or GH deficiency and healthy subjects were 8.7 %/- 0.7 (n = 25), 0.24 +/- 0.02 (n = 25), and 1.15 +/- 0.11 U/ml, respectively. The correlation coefficient between immunoreactive SM-A and SM-A by radioreceptor assay was highly significant (r = 0.93), although the potency ratio of SM-A between the two groups of patients was higher in the RIA than in the radioreceptor assay. Gel chromatography revealed that SM-A in acromegalic serum is bound to a carrier protein which is absent in patients with GH deficiency. After gel chromatography at low pH, 90% of applied immunoreactive SM-A was recovered in the low molecular weight fraction and consisted mainly of neutral polypeptides."}
{"id": "PMID:218987", "title": "Plasma corticotropin and cortisol in patients with pituitary adenomas.", "content": "Plasma ACTH and cortisol were measured during insulin-induced hypoglycemia in 39 patients with a pituitary adenoma or after hypophysectomy and in 26 healthy persons. Adrenocortical insufficiency was defined as failure to increase plasma cortisol to at least 500 nmol/liter (18 microgram/dl) during hypoglycemia. No proper distinction was possible between patients with normal and impaired cortisol response to hypoglycemia on the basis of the ACTH results. When all 39 patients were compared to the 26 controls, the cortisol results differed significantly, but those of ACTH did not. These results demonstrate a limited value of ACTH measurements in secondary adrenocortical failure.", "contents": "Plasma corticotropin and cortisol in patients with pituitary adenomas. Plasma ACTH and cortisol were measured during insulin-induced hypoglycemia in 39 patients with a pituitary adenoma or after hypophysectomy and in 26 healthy persons. Adrenocortical insufficiency was defined as failure to increase plasma cortisol to at least 500 nmol/liter (18 microgram/dl) during hypoglycemia. No proper distinction was possible between patients with normal and impaired cortisol response to hypoglycemia on the basis of the ACTH results. When all 39 patients were compared to the 26 controls, the cortisol results differed significantly, but those of ACTH did not. These results demonstrate a limited value of ACTH measurements in secondary adrenocortical failure."}
{"id": "PMID:218988", "title": "\"Acquired\" adrenal hyperplasia with 21-hydroxylase deficiency is not the same genetic disorders as congenital adrenal hyperplasia.", "content": "Hormonal studies and HLA genotyping were performed on the family of a patient with \"acquired\" adrenal hyperplasia (AAH) due to 21-hydroxylase deficiency. The results of these studies suggest that \"AAH\", is not the same genetic disease as CAH.", "contents": "\"Acquired\" adrenal hyperplasia with 21-hydroxylase deficiency is not the same genetic disorders as congenital adrenal hyperplasia. Hormonal studies and HLA genotyping were performed on the family of a patient with \"acquired\" adrenal hyperplasia (AAH) due to 21-hydroxylase deficiency. The results of these studies suggest that \"AAH\", is not the same genetic disease as CAH."}
{"id": "PMID:218989", "title": "Serum somatomedin A in chronic renal failure.", "content": "The serum levels of somatomedin A, determined by radioreceptor assay, were significantly higher in 57 adult patients with chronic renal failure (X = 2.57 +/- 0.12 U/ml) than in healthy subjects (n = 131; X = 0.77 +/- 0.02 U/ml). A positive correlation was found between somatomedin A and creatinine levels (r = 0.33), but somatomedin A levels did not decrease after hemodialysis. A reduction was only observed after successful renal allografting. Immunoreactive somatomedin A was also found to be increased in patients with chronic renal failure (X = 2.61 +/- 0.21 U/ml), whereas low levels were obtained by the chick bioassay. However, after separating the inhibitory factors from the stimulatory factors by gel chromatography at neutral pH, uremic serum was shown to contain increased levels of somatomedin activity. Although all somatomedin A, determined by different techniques, was present in high molecular forms, the elution pattern differed from that seen in patients with acromegaly.", "contents": "Serum somatomedin A in chronic renal failure. The serum levels of somatomedin A, determined by radioreceptor assay, were significantly higher in 57 adult patients with chronic renal failure (X = 2.57 +/- 0.12 U/ml) than in healthy subjects (n = 131; X = 0.77 +/- 0.02 U/ml). A positive correlation was found between somatomedin A and creatinine levels (r = 0.33), but somatomedin A levels did not decrease after hemodialysis. A reduction was only observed after successful renal allografting. Immunoreactive somatomedin A was also found to be increased in patients with chronic renal failure (X = 2.61 +/- 0.21 U/ml), whereas low levels were obtained by the chick bioassay. However, after separating the inhibitory factors from the stimulatory factors by gel chromatography at neutral pH, uremic serum was shown to contain increased levels of somatomedin activity. Although all somatomedin A, determined by different techniques, was present in high molecular forms, the elution pattern differed from that seen in patients with acromegaly."}
{"id": "PMID:218990", "title": "Correlation between thyrotropin-displacing activity and human thyroid-stimulating activity by immunoglobulins from patients with Graves' disease and other thyroid disorders.", "content": "Several reports have been published on the anti-TSH receptor antibody in putative autoimmune thyroid disorders using a radioreceptor assay. We have carried out correlative studies between the ability of serum immunoglobulins to displace radiolabeled TSH from the thyroid plasma membrane receptor [TSH-displacing activity (TDA)] and that of actual stimulation of the human thyroid gland [human thyroid-stimulating activity (hTSA)] in Graves' and other thyroid diseases and in control subjects. TDA was assayed by the use of a radioligand technique, while the activation of adenylate cyclase in human thyroid slices was measured as an index of hTSA. The same immunoglobulins were employed for both assays. In this series, positive TDA and hTSA values were found in 70.4% and 81.5% of the samples in active untreated Graves' disease, respectively. Samples from normal persons and from several patients with toxic nodular goiter gave generally negative results in both assays; in a small proportion of patients with either subacute thyroiditis or Hashimoto's thyroiditis, the TDA was positive but hTSA proved to be negative. In Graves' disease (including those patients on propylthiouracil) in remission and treated with 131I, the correlation between TDA and hTSA was not significant (r = 0.309; P greater than 0.1); even when the procedures were compared in the untreated group alone, there was no significant correlation between the two activities (r = 0.309, P greater than 0.1). These studies indicate that 1) significant TDA and hTSA are observed in Graves' disease; nevertheless, the correlation between them is not significant; 2) the hTSA assay appears to be more sensitive and specific than the TDA assay; and 3) TDA may not be synonymous with thyroid stimulation.", "contents": "Correlation between thyrotropin-displacing activity and human thyroid-stimulating activity by immunoglobulins from patients with Graves' disease and other thyroid disorders. Several reports have been published on the anti-TSH receptor antibody in putative autoimmune thyroid disorders using a radioreceptor assay. We have carried out correlative studies between the ability of serum immunoglobulins to displace radiolabeled TSH from the thyroid plasma membrane receptor [TSH-displacing activity (TDA)] and that of actual stimulation of the human thyroid gland [human thyroid-stimulating activity (hTSA)] in Graves' and other thyroid diseases and in control subjects. TDA was assayed by the use of a radioligand technique, while the activation of adenylate cyclase in human thyroid slices was measured as an index of hTSA. The same immunoglobulins were employed for both assays. In this series, positive TDA and hTSA values were found in 70.4% and 81.5% of the samples in active untreated Graves' disease, respectively. Samples from normal persons and from several patients with toxic nodular goiter gave generally negative results in both assays; in a small proportion of patients with either subacute thyroiditis or Hashimoto's thyroiditis, the TDA was positive but hTSA proved to be negative. In Graves' disease (including those patients on propylthiouracil) in remission and treated with 131I, the correlation between TDA and hTSA was not significant (r = 0.309; P greater than 0.1); even when the procedures were compared in the untreated group alone, there was no significant correlation between the two activities (r = 0.309, P greater than 0.1). These studies indicate that 1) significant TDA and hTSA are observed in Graves' disease; nevertheless, the correlation between them is not significant; 2) the hTSA assay appears to be more sensitive and specific than the TDA assay; and 3) TDA may not be synonymous with thyroid stimulation."}
{"id": "PMID:218991", "title": "The effects of L-dopa on in vitro and in vivo calcitonin release from medullary thyroid carcinoma.", "content": "The in vivo and in vitro effects of the dopamine precursor L-dopa on basal and stimulated calcitonin release from medullary thyroid carcinoma have been studied. In six studies of five patients, including 7- to 8-h control and test periods, oral L-dopa depressed basal calcitonin secretion by an average of 35%; the peak effects occurred within 30 min of drug administration and lasted for as long as 4 h. In seven of eight patients with medullary thyroid carcinoma (three infused with calcium and five with pentagastrin), L-dopa inhibited to varying degrees peak levels of stimulated calcitonin release and total calcitonin secretion; basal calcitonin levels, where directly tested, also again generally fell after L-dopa by an average of 50%. In a short term organ culture system using medullary thyroid carcinoma tissues, calcitonin secretion into the medium was linear with time for 2 h and could be stimulated by dibutyryl cAMP and pentagastrin. L-Dopa, in concentrations from 0.5--3.0 mM, inhibited basal calcitonin secretion (ranging from 25--55%). Addition of the L-dopa decarboxylase inhibitor, alpha-methyldopa, abolished the inhibitory effects of L-dopa. Another L-dopa decarboxylase inhibitor, carbidopa, stimulated calcitonin secretion in vitro; this effect may be independent of the L-dopa decarboxylase-inhibiting properties of this drug since alpha-methyldopa alone did not stimulate calcitonin secretion. It is concluded that the amine precursor L-dopa inhibits calcitonin release in patients with medullary thyroid carcinoma; the in vitro studies suggest that a portion of this effect may involve direct metabolism of L-dopa to dopamine in the tumor tissue itself. The importance of considering the uptake of amine precursors and the subsequent metabolism of these compounds as a modulating site for peptide hormone release from peripheral endocrine tissues is stressed.", "contents": "The effects of L-dopa on in vitro and in vivo calcitonin release from medullary thyroid carcinoma. The in vivo and in vitro effects of the dopamine precursor L-dopa on basal and stimulated calcitonin release from medullary thyroid carcinoma have been studied. In six studies of five patients, including 7- to 8-h control and test periods, oral L-dopa depressed basal calcitonin secretion by an average of 35%; the peak effects occurred within 30 min of drug administration and lasted for as long as 4 h. In seven of eight patients with medullary thyroid carcinoma (three infused with calcium and five with pentagastrin), L-dopa inhibited to varying degrees peak levels of stimulated calcitonin release and total calcitonin secretion; basal calcitonin levels, where directly tested, also again generally fell after L-dopa by an average of 50%. In a short term organ culture system using medullary thyroid carcinoma tissues, calcitonin secretion into the medium was linear with time for 2 h and could be stimulated by dibutyryl cAMP and pentagastrin. L-Dopa, in concentrations from 0.5--3.0 mM, inhibited basal calcitonin secretion (ranging from 25--55%). Addition of the L-dopa decarboxylase inhibitor, alpha-methyldopa, abolished the inhibitory effects of L-dopa. Another L-dopa decarboxylase inhibitor, carbidopa, stimulated calcitonin secretion in vitro; this effect may be independent of the L-dopa decarboxylase-inhibiting properties of this drug since alpha-methyldopa alone did not stimulate calcitonin secretion. It is concluded that the amine precursor L-dopa inhibits calcitonin release in patients with medullary thyroid carcinoma; the in vitro studies suggest that a portion of this effect may involve direct metabolism of L-dopa to dopamine in the tumor tissue itself. The importance of considering the uptake of amine precursors and the subsequent metabolism of these compounds as a modulating site for peptide hormone release from peripheral endocrine tissues is stressed."}
{"id": "PMID:218992", "title": "Regulation of lipolysis by human adipose tissue in hyperthyroidism.", "content": "The effects of noradrenaline (NA) and isopropyl-noradrenaline (ISNA) on glycerol release and cAMP levels in sc adipose tissue were studied in vitro in 27 patients with hyperthyroidism. In 11 patients, the studies were repeated after 6--12 months of treatment for hyperthyroidism. A third group comprised 21 euthyroid patients otherwise healthy except for morbid obesity. The lipolytic response to ISNA, observed in untreated thyrotoxic patients, was found to be reduced by 30% when the patients were reexamined after treatment for thyrotoxicosis. This reduction was attributable to a decrease in the cAMP level. This was observed whether adipose tissue was incubated in the presence or absence of a phosphodiesterase inhibitor, theophylline. Both NA and ISNA induced 50% more rapid glycerol release and 4 times higher cAMP levels in adipose tissue of the thyrotoxic subjects than in the obese euthyroid patients. A positive correlation between tissue cAMP and glycerol release, on one hand, and mean fat cell size, on the other hand, was observed in treated thyrotoxic patients and obese euthyroid patients but was not recorded in the untreated hyperthyroid patients. The basal rate of lipolysis was not altered in thyrotoxicosis. The results suggest that the enhanced lipolytic response to catecholamines in adipose tissue of hyperthyroid patients is due to increased beta-adrenergic responsiveness. In addition, a disruption in subsequent stages of the regulatory pathway at the level of protein kinase or hormone-sensitive lipase also seems possible.", "contents": "Regulation of lipolysis by human adipose tissue in hyperthyroidism. The effects of noradrenaline (NA) and isopropyl-noradrenaline (ISNA) on glycerol release and cAMP levels in sc adipose tissue were studied in vitro in 27 patients with hyperthyroidism. In 11 patients, the studies were repeated after 6--12 months of treatment for hyperthyroidism. A third group comprised 21 euthyroid patients otherwise healthy except for morbid obesity. The lipolytic response to ISNA, observed in untreated thyrotoxic patients, was found to be reduced by 30% when the patients were reexamined after treatment for thyrotoxicosis. This reduction was attributable to a decrease in the cAMP level. This was observed whether adipose tissue was incubated in the presence or absence of a phosphodiesterase inhibitor, theophylline. Both NA and ISNA induced 50% more rapid glycerol release and 4 times higher cAMP levels in adipose tissue of the thyrotoxic subjects than in the obese euthyroid patients. A positive correlation between tissue cAMP and glycerol release, on one hand, and mean fat cell size, on the other hand, was observed in treated thyrotoxic patients and obese euthyroid patients but was not recorded in the untreated hyperthyroid patients. The basal rate of lipolysis was not altered in thyrotoxicosis. The results suggest that the enhanced lipolytic response to catecholamines in adipose tissue of hyperthyroid patients is due to increased beta-adrenergic responsiveness. In addition, a disruption in subsequent stages of the regulatory pathway at the level of protein kinase or hormone-sensitive lipase also seems possible."}
{"id": "PMID:218993", "title": "Inhibition of human chorionic gonadotropin-induced progesterone synthesis by estradiol in isolated human luteal cells.", "content": "The purpose of this study was to determine whether estrogens exerted a direct inhibitory effect on progesterone synthesis in isolated human luteal cells in vitro. It was found that hCG stimulated progesterone synthesis by luteal cells, obtained from corpora lutea of the menstrual cycle, whereas cells isolated from corpora lutea of pregnancy were unresponsive to exogenous hCG. Estradiol markedly inhibited (P less than 0.001) this hCG effect in luteal cells of the menstrual cycle, and this inhibition was dose dependent. Estradiol did not block the stimulation of cAMP accumulated by hCG in the luteal cells of the cycle but did inhibit the stimulatory effect of dibutyryl cAMP on progesterone synthesis. These data suggest that estrogens may directly cause functional luteolysis in the human and that its site of action may be after the accumulation of cAMP.", "contents": "Inhibition of human chorionic gonadotropin-induced progesterone synthesis by estradiol in isolated human luteal cells. The purpose of this study was to determine whether estrogens exerted a direct inhibitory effect on progesterone synthesis in isolated human luteal cells in vitro. It was found that hCG stimulated progesterone synthesis by luteal cells, obtained from corpora lutea of the menstrual cycle, whereas cells isolated from corpora lutea of pregnancy were unresponsive to exogenous hCG. Estradiol markedly inhibited (P less than 0.001) this hCG effect in luteal cells of the menstrual cycle, and this inhibition was dose dependent. Estradiol did not block the stimulation of cAMP accumulated by hCG in the luteal cells of the cycle but did inhibit the stimulatory effect of dibutyryl cAMP on progesterone synthesis. These data suggest that estrogens may directly cause functional luteolysis in the human and that its site of action may be after the accumulation of cAMP."}
{"id": "PMID:218994", "title": "Adrenocorticotropin-stimulated secretion of aldosterone and cortisol, computed from plasma and red blood cell measurements.", "content": "The dynamic response of the adrenal cortex to ACTH infusion is analyzed by simulating the distribution, binding, and metabolism of cortisol and aldosterone in a multicompartmental model. The model includes the effects of temperature and cortisol concentration on aldosterone binding in plasma and the distribution between plasma and red blood cells, as verified by new observations. The secretion rates of cortisol and aldosterone were computed from serial measurements of plasma concentrations of endogenous steroids and infused tracers. The model was validated by observations after iv injection of a bolus of cortisol. Nineteen normal volunteers were studied on the fourth day on a diet containing 10 meq sodium. Endogenous ACTH was suppressed by dexamethasone, and alpha-1-24ACTH was infused at two different rates in various sequences over a 4-h period. During each hour of constant ACTH infusion, plasma cortisol continued to increase, while plasma aldosterone rose quickly, reaching a plateau within 20--30 min. Cortisol secretion approached a maximim rate after 20--30 min of ACTH infusion; the continued increase of plasma cortisol resulted from the slow equilibrium with other compartments. Aldosterone secretion rose quickly to a peak and then declined to a lower level after 20 min of ACTH infusion; the lower rate of secretion was maintained for the duration of the constant infusion of ACTH, falling abruptly within a few minutes after stopping the infusion. The characteristic differences in plasma steroid responses to various sequences of ACTH infusions can be explained by the more rapid changes in aldosterone secretion and the different clearance rates of cortisol and aldosterone, which vary with plasma cortisol concentration. The temperature at which blood is separated significantly affects plasma aldosterone measurements.", "contents": "Adrenocorticotropin-stimulated secretion of aldosterone and cortisol, computed from plasma and red blood cell measurements. The dynamic response of the adrenal cortex to ACTH infusion is analyzed by simulating the distribution, binding, and metabolism of cortisol and aldosterone in a multicompartmental model. The model includes the effects of temperature and cortisol concentration on aldosterone binding in plasma and the distribution between plasma and red blood cells, as verified by new observations. The secretion rates of cortisol and aldosterone were computed from serial measurements of plasma concentrations of endogenous steroids and infused tracers. The model was validated by observations after iv injection of a bolus of cortisol. Nineteen normal volunteers were studied on the fourth day on a diet containing 10 meq sodium. Endogenous ACTH was suppressed by dexamethasone, and alpha-1-24ACTH was infused at two different rates in various sequences over a 4-h period. During each hour of constant ACTH infusion, plasma cortisol continued to increase, while plasma aldosterone rose quickly, reaching a plateau within 20--30 min. Cortisol secretion approached a maximim rate after 20--30 min of ACTH infusion; the continued increase of plasma cortisol resulted from the slow equilibrium with other compartments. Aldosterone secretion rose quickly to a peak and then declined to a lower level after 20 min of ACTH infusion; the lower rate of secretion was maintained for the duration of the constant infusion of ACTH, falling abruptly within a few minutes after stopping the infusion. The characteristic differences in plasma steroid responses to various sequences of ACTH infusions can be explained by the more rapid changes in aldosterone secretion and the different clearance rates of cortisol and aldosterone, which vary with plasma cortisol concentration. The temperature at which blood is separated significantly affects plasma aldosterone measurements."}
{"id": "PMID:218995", "title": "Increased somatomedin receptor sites in newborn circulating mononuclear cells.", "content": "To evaluate the potential role of somatomedin as a growth factor in fetal development, we studied somatomedin receptors on circulating mononuclear cells from placental cord blood from 13 normal term newborns. Twelve healthy young adults served as controls. By radioreceptor assay of acid-chromatographed plasma, total somatomedin peptide content of cord blood was 0.30 +/- 0.02 U/ml (mean +/- SEM) compared to 1.12 +/- 0.08 U/ml for adults. Specific binding of [125I]somatomedin C to 50 X 10(6) mononuclear cells was 11.38 +/- 0.74% for newborns and 6.67 +/- 0.51% for adults. This increase in specific binding appears to be due to an increased number of receptor sites per cell. These data support a hypothesis of increased fetal sensitivity to somatomedin.", "contents": "Increased somatomedin receptor sites in newborn circulating mononuclear cells. To evaluate the potential role of somatomedin as a growth factor in fetal development, we studied somatomedin receptors on circulating mononuclear cells from placental cord blood from 13 normal term newborns. Twelve healthy young adults served as controls. By radioreceptor assay of acid-chromatographed plasma, total somatomedin peptide content of cord blood was 0.30 +/- 0.02 U/ml (mean +/- SEM) compared to 1.12 +/- 0.08 U/ml for adults. Specific binding of [125I]somatomedin C to 50 X 10(6) mononuclear cells was 11.38 +/- 0.74% for newborns and 6.67 +/- 0.51% for adults. This increase in specific binding appears to be due to an increased number of receptor sites per cell. These data support a hypothesis of increased fetal sensitivity to somatomedin."}
{"id": "PMID:218996", "title": "6 beta-Hydroxycortisol excretion in hypercortisolemic states.", "content": "Urinary 6beta-hydroxycortisol (6betaOHF) excretion was measured and compared with free cortisol and 17-hydroxycorticosteroid (17OH) excretion in normal children, patients with Cushing's syndrome or disease (CSD), and patients during cortisol therapy. Normal 6betaOHF excretion in children was 0.23 +/- 0.03 mg/m2/24 h (mean +/- SE). No sex difference was found. ACTH infusion (40 U/day for 5 days) and high dose cortisol altered the 6 betaOHF:17OH ratio so that it was indistinguishable from the ratio seen in CSD. The fact that both Cushing's disease and high dose cortisol therapy caused the same change in the 6 betaOHF:17OH ratio suggests that cortisol and not ACTH induced 6beta-hydroxylase in hypercortisolemic subjects. Since the 6betaOHF:17OH ratio in CSD patients was always well above the normal range, measurement of 6betaOHF excretion was a better and more rapid test for chronic hypercortisolemia than urinary 17OH or free cortisol. Thus, measurement of urinary 6betaOHF is suggested as a good diagnostic test for hypercortisolemic states.", "contents": "6 beta-Hydroxycortisol excretion in hypercortisolemic states. Urinary 6beta-hydroxycortisol (6betaOHF) excretion was measured and compared with free cortisol and 17-hydroxycorticosteroid (17OH) excretion in normal children, patients with Cushing's syndrome or disease (CSD), and patients during cortisol therapy. Normal 6betaOHF excretion in children was 0.23 +/- 0.03 mg/m2/24 h (mean +/- SE). No sex difference was found. ACTH infusion (40 U/day for 5 days) and high dose cortisol altered the 6 betaOHF:17OH ratio so that it was indistinguishable from the ratio seen in CSD. The fact that both Cushing's disease and high dose cortisol therapy caused the same change in the 6 betaOHF:17OH ratio suggests that cortisol and not ACTH induced 6beta-hydroxylase in hypercortisolemic subjects. Since the 6betaOHF:17OH ratio in CSD patients was always well above the normal range, measurement of 6betaOHF excretion was a better and more rapid test for chronic hypercortisolemia than urinary 17OH or free cortisol. Thus, measurement of urinary 6betaOHF is suggested as a good diagnostic test for hypercortisolemic states."}
{"id": "PMID:218997", "title": "Predicting the response of growth hormone-deficient children to long term treatment with human growth hormone.", "content": "A previous study showed that when GH-deficient children below the third percentile in height are treated with 0.168 U human GH (hGH)/kg BW3/4 for 10 days, their height increases by 0.3--1.9 cm during the next 8 weeks. The present study determined whether this acute response would predict the child's long term response to 1 yr of treatment with the same dose of hGH given three times a week. Eighteen GH-deficient children and adolescents, aged 8--16 yr, were measured every 2 weeks over 108 weeks. After a control period of 12 weeks (period 1), the patient received hGH for 10 days. During the remainder of the 12 weeks of period 2 and during the next 12 weeks (period 3), hGH was not given. Patients recieved hGH three times a week during periods 4 and 5 (24 weeks each). Periods 6 and 7 (12 weeks each) were posttreatment control periods. During periods 1, 3, 6, and 7, rate of growth was less than 0.2 cm/month. During period 2, the rate ranged between 0.1--0.8 cm/month. During periods 4 and 5, the growth rate ranged from 0.2--1.0 cm/month. Rate of growth during periods 4 and 5 (y) was related to rate during period 2 (x) by the equation y = 0.027 + 1.17 x. The correlation coefficient between y and x was 0.91 (P less than 0.001). The increment in height which will occur during 48 weeks of treatment can be predicted from the response to 10 days of treatment by this equation. The SE of the prediction averages +/- 1.2 cm/yr.", "contents": "Predicting the response of growth hormone-deficient children to long term treatment with human growth hormone. A previous study showed that when GH-deficient children below the third percentile in height are treated with 0.168 U human GH (hGH)/kg BW3/4 for 10 days, their height increases by 0.3--1.9 cm during the next 8 weeks. The present study determined whether this acute response would predict the child's long term response to 1 yr of treatment with the same dose of hGH given three times a week. Eighteen GH-deficient children and adolescents, aged 8--16 yr, were measured every 2 weeks over 108 weeks. After a control period of 12 weeks (period 1), the patient received hGH for 10 days. During the remainder of the 12 weeks of period 2 and during the next 12 weeks (period 3), hGH was not given. Patients recieved hGH three times a week during periods 4 and 5 (24 weeks each). Periods 6 and 7 (12 weeks each) were posttreatment control periods. During periods 1, 3, 6, and 7, rate of growth was less than 0.2 cm/month. During period 2, the rate ranged between 0.1--0.8 cm/month. During periods 4 and 5, the growth rate ranged from 0.2--1.0 cm/month. Rate of growth during periods 4 and 5 (y) was related to rate during period 2 (x) by the equation y = 0.027 + 1.17 x. The correlation coefficient between y and x was 0.91 (P less than 0.001). The increment in height which will occur during 48 weeks of treatment can be predicted from the response to 10 days of treatment by this equation. The SE of the prediction averages +/- 1.2 cm/yr."}
{"id": "PMID:218998", "title": "Beta-Adrenergic receptors of human lymphocytes are unaltered by hyperthyroidism.", "content": "Lymphocytes from 12 patients with untreated hyperthyroidism were compared to lymphocytes from age- and sex-matched euthyroid control subjects to test the hypothesis that alterations in beta-adrenergic response mechanisms occur in human hyperthyroidism. The binding of (-)[3H]dihydroalprenolol, a compound previously shown in these cells to label binding sites having the characteristics of beta-adrenergic receptors, was assayed and no significant difference was found between the two groups. In addition, the accumulation of cAMP in response to isoproterenol was determined by RIA and, again, no difference was found.", "contents": "Beta-Adrenergic receptors of human lymphocytes are unaltered by hyperthyroidism. Lymphocytes from 12 patients with untreated hyperthyroidism were compared to lymphocytes from age- and sex-matched euthyroid control subjects to test the hypothesis that alterations in beta-adrenergic response mechanisms occur in human hyperthyroidism. The binding of (-)[3H]dihydroalprenolol, a compound previously shown in these cells to label binding sites having the characteristics of beta-adrenergic receptors, was assayed and no significant difference was found between the two groups. In addition, the accumulation of cAMP in response to isoproterenol was determined by RIA and, again, no difference was found."}
{"id": "PMID:219005", "title": "Virilizing adrenal adenoma stimulated by dexamethasone in a middle-aged woman.", "content": "In a middle-aged woman with virilizing adenoma, 2 mg dexamethasone increased urinary excretion of 17-ketosteroids (17-KS) and 17-hydroxycorticosteroids, whereas 8 mg dexamethasone increased urinary excretion only of 17-KS. With discontinuation of dexamethasone, 17-KS excretion returned to the predexamethasone level. Dexamethasone depressed the basal level of cAMP synthesis and basal testosterone production by the normal adrenal tissue in vitro. Dexamethasone also depressed the increase of cAMP produced by ACTH in the normal tissue. In contrast, dexamethasone increased basal cAMP synthesis and stimulated testosterone secretion in the tumor tissue. ACTH and dexamethasone were additive in their effects on cAMP and testosterone in the tumor tissue. It is suggested that dexamethasone acted directly on the adrenal tumor to stimulate steroid secretion in this patients.", "contents": "Virilizing adrenal adenoma stimulated by dexamethasone in a middle-aged woman. In a middle-aged woman with virilizing adenoma, 2 mg dexamethasone increased urinary excretion of 17-ketosteroids (17-KS) and 17-hydroxycorticosteroids, whereas 8 mg dexamethasone increased urinary excretion only of 17-KS. With discontinuation of dexamethasone, 17-KS excretion returned to the predexamethasone level. Dexamethasone depressed the basal level of cAMP synthesis and basal testosterone production by the normal adrenal tissue in vitro. Dexamethasone also depressed the increase of cAMP produced by ACTH in the normal tissue. In contrast, dexamethasone increased basal cAMP synthesis and stimulated testosterone secretion in the tumor tissue. ACTH and dexamethasone were additive in their effects on cAMP and testosterone in the tumor tissue. It is suggested that dexamethasone acted directly on the adrenal tumor to stimulate steroid secretion in this patients."}
{"id": "PMID:219006", "title": "Epidermal growth factor (urogastrone) in human tissues.", "content": "Human epidermal growth factor (hEGF), which stimulates the growth of a variety of tissues, was first isolated from mouse submandibular glands, but is also excreted in large amounts (about 50 micrograms/day) in human urine and is probably identical to human beta-urogastrone (hUG), a potent inhibitor of stimulated gastric acid secretion. However, the primary tissue source of hEGF/hUG is as yet unknown. The hEGF/hUG in homogenates of human salivary glands and a wide variety of other endocrine and nonendocrine tissues was extracted by Amberlite CG-50 cation exchange chromatography and immune affinity chromatography using the immunoglobulin fraction of rabbit anti-hEGF serum covalently bound to agarose. The extracts were subjected to homologous hEGF RIA. Immunoreactive hEGF was found in extracts of adult submandibular gland, thyroid gland, duodenum, jejunum, and kidney, but not in several fetal tissues. The tissue immunoreactive hEGF was similar to standard hEGF in terms of immunoreactivity and elution from Sephadex G-50 Fine resin, but its concentrations were very low (1.3-5.5 ng/g wet tissue). Thus, it is not certain that these tissues represent the only source of the large amounts of hEGF/hUG that appear to be filtered by the kidneys each day.", "contents": "Epidermal growth factor (urogastrone) in human tissues. Human epidermal growth factor (hEGF), which stimulates the growth of a variety of tissues, was first isolated from mouse submandibular glands, but is also excreted in large amounts (about 50 micrograms/day) in human urine and is probably identical to human beta-urogastrone (hUG), a potent inhibitor of stimulated gastric acid secretion. However, the primary tissue source of hEGF/hUG is as yet unknown. The hEGF/hUG in homogenates of human salivary glands and a wide variety of other endocrine and nonendocrine tissues was extracted by Amberlite CG-50 cation exchange chromatography and immune affinity chromatography using the immunoglobulin fraction of rabbit anti-hEGF serum covalently bound to agarose. The extracts were subjected to homologous hEGF RIA. Immunoreactive hEGF was found in extracts of adult submandibular gland, thyroid gland, duodenum, jejunum, and kidney, but not in several fetal tissues. The tissue immunoreactive hEGF was similar to standard hEGF in terms of immunoreactivity and elution from Sephadex G-50 Fine resin, but its concentrations were very low (1.3-5.5 ng/g wet tissue). Thus, it is not certain that these tissues represent the only source of the large amounts of hEGF/hUG that appear to be filtered by the kidneys each day."}
{"id": "PMID:219007", "title": "Circadian cortisol secretory rhythms in Cushing's disease.", "content": "Plasma cortisol was measured at 20-min intervals for 24 h in eight patients with Cushing's disease and ACTH-secreting pituitary tumors. The 24-h mean (+/- SD) cortisol level was 25.6 +/- 11.3 microgram/dl (range, 15.5--40.6), which was significantly higher than the level of normal control subjects (P less than 0.01). The 24-h mean ACTH level varied between 22--107 pg/ml, with a mean +/- SD of 63.4 +/- 27.2. The mean ACTH level was higher than that of the control subjects but the difference was not statistically significant. The 24-h cortisol secretory pattern was characterized by an absence of the normal circadian variation and a failure of the plasma cortisol level to fall to less than 2 microgram/dl between 2300--0300 h. The coefficient of variation, an expression of the amplitude of cortisol secretory episodes, was significantly decreased in patients with Cushing's disease compared to normal control subjects; there was no significant difference in the number of cortisol secretory episodes in the patients vs. control subjects. Three of the patients were restudied after successful resection of their ACTH-secreting pituitary tumors. Two showed normalization of their 24-h circadian cortisol patterns and normal metyrapone responses. In the third, the 24-h mean cortisol level was normal, but the circadian cortisol rhythm remained abnormal. This patient had diminished ACTH reserve, demonstrated by a subnormal response to metyrapone. Additional studies will be required to determine if normalization of the circadian cortisol rhythm occurs in all patients with Cushing's disease who are cured after transsphenoidal microsurgery and who also show normal ACTH reserve.", "contents": "Circadian cortisol secretory rhythms in Cushing's disease. Plasma cortisol was measured at 20-min intervals for 24 h in eight patients with Cushing's disease and ACTH-secreting pituitary tumors. The 24-h mean (+/- SD) cortisol level was 25.6 +/- 11.3 microgram/dl (range, 15.5--40.6), which was significantly higher than the level of normal control subjects (P less than 0.01). The 24-h mean ACTH level varied between 22--107 pg/ml, with a mean +/- SD of 63.4 +/- 27.2. The mean ACTH level was higher than that of the control subjects but the difference was not statistically significant. The 24-h cortisol secretory pattern was characterized by an absence of the normal circadian variation and a failure of the plasma cortisol level to fall to less than 2 microgram/dl between 2300--0300 h. The coefficient of variation, an expression of the amplitude of cortisol secretory episodes, was significantly decreased in patients with Cushing's disease compared to normal control subjects; there was no significant difference in the number of cortisol secretory episodes in the patients vs. control subjects. Three of the patients were restudied after successful resection of their ACTH-secreting pituitary tumors. Two showed normalization of their 24-h circadian cortisol patterns and normal metyrapone responses. In the third, the 24-h mean cortisol level was normal, but the circadian cortisol rhythm remained abnormal. This patient had diminished ACTH reserve, demonstrated by a subnormal response to metyrapone. Additional studies will be required to determine if normalization of the circadian cortisol rhythm occurs in all patients with Cushing's disease who are cured after transsphenoidal microsurgery and who also show normal ACTH reserve."}
{"id": "PMID:219010", "title": "Direct inhibitory effect of dexamethasone on steroidogenesis of human adrenal in vivo.", "content": "A rapid ACTH test was used to investigate the direct effect of glucocorticoid on the steroidogenesis by the adrenal cortex in man. The plasma cortisol response to 250 microgram iv synthetic alpha-ACTH-(1--24) (Cortrosyn) was determined in normal subjects pretreated with 2 and 12 mg dexamethasone. The 15- and 30-min increments in plasma cortisol levels in response to ACTH injection after pretreatment with 12 mg dexamethasone were significantly suppressed compared to values obtained after pretreatment with 2 mg dexamethasone. The present study suggests that there is a direct inhibitory effect of glucocorticoid on adrenocortical steroidogenesis in man.", "contents": "Direct inhibitory effect of dexamethasone on steroidogenesis of human adrenal in vivo. A rapid ACTH test was used to investigate the direct effect of glucocorticoid on the steroidogenesis by the adrenal cortex in man. The plasma cortisol response to 250 microgram iv synthetic alpha-ACTH-(1--24) (Cortrosyn) was determined in normal subjects pretreated with 2 and 12 mg dexamethasone. The 15- and 30-min increments in plasma cortisol levels in response to ACTH injection after pretreatment with 12 mg dexamethasone were significantly suppressed compared to values obtained after pretreatment with 2 mg dexamethasone. The present study suggests that there is a direct inhibitory effect of glucocorticoid on adrenocortical steroidogenesis in man."}
{"id": "PMID:219011", "title": "Hemodialysis-resistant hypertension: control with an orally active inhibitor of angiotensin-converting enzyme.", "content": "In two patients with end stage renal disease and dialysis-resistant hypertension, the orally active inhibitor of angiotensin-converting enzyme, captopril (SQ14,225; 2-D-methyl-3-mercaptopropranoyl-L-proline, dramatically lowered blood pressure both before and during dialysis. This agent holds promise as an alternate to bilateral nephrectomy in such patients.", "contents": "Hemodialysis-resistant hypertension: control with an orally active inhibitor of angiotensin-converting enzyme. In two patients with end stage renal disease and dialysis-resistant hypertension, the orally active inhibitor of angiotensin-converting enzyme, captopril (SQ14,225; 2-D-methyl-3-mercaptopropranoyl-L-proline, dramatically lowered blood pressure both before and during dialysis. This agent holds promise as an alternate to bilateral nephrectomy in such patients."}
{"id": "PMID:219012", "title": "Lack of a diurnal plasma adenosine 3',5'-monophosphate rhythm.", "content": "Plasma cAMP levels were measured using a protein-binding radioassay in nine healthy volunteer subjects over a period of 24 h under standardized conditions and also after an hour of orthostatism. No circadian variations of cAMP in plasma were observed. After orthostatism, however, there was a significant rise in cAMP concentrations.", "contents": "Lack of a diurnal plasma adenosine 3',5'-monophosphate rhythm. Plasma cAMP levels were measured using a protein-binding radioassay in nine healthy volunteer subjects over a period of 24 h under standardized conditions and also after an hour of orthostatism. No circadian variations of cAMP in plasma were observed. After orthostatism, however, there was a significant rise in cAMP concentrations."}
{"id": "PMID:219013", "title": "Phentolamine and the action of somatostatin in man.", "content": "The inhibition by somatostatin (SRIF) of basal and arginine-stimulated glucagon, insulin, and glucose levels was compared with that obtained when SRIF was preceded by alpha-adrenergic blockade with phentolamine. No noteworthy differences were observed, except that the characteristic rebound of insulin upon discontinuation of SRIF was significantly lower with phentolamine (P less than 0.01). These results indicate that inhibition of basal and arginine-stimulated glucagon and insulin secretion by SRIF in man is not mediated through activation by alpha-adrenergic receptors.", "contents": "Phentolamine and the action of somatostatin in man. The inhibition by somatostatin (SRIF) of basal and arginine-stimulated glucagon, insulin, and glucose levels was compared with that obtained when SRIF was preceded by alpha-adrenergic blockade with phentolamine. No noteworthy differences were observed, except that the characteristic rebound of insulin upon discontinuation of SRIF was significantly lower with phentolamine (P less than 0.01). These results indicate that inhibition of basal and arginine-stimulated glucagon and insulin secretion by SRIF in man is not mediated through activation by alpha-adrenergic receptors."}
{"id": "PMID:219014", "title": "Regulatory role of triiodothyronine in the degradation of low density lipoprotein by cultured human skin fibroblasts.", "content": "Degradation of [125I]-labeled low density lipoprotein (LDL) by cultured normal human skin fibroblasts was enhanced by exposure to concentrations of L-triiodothyronine (T3) spanning the physiological range. Analysis of LDL concentration curves suggests that T3 may increase LDL receptor number rather than alter the affinity of LDL for its receptor. No effect of T3 on LDL degradation was observed in receptor negative cells. Thus thyroid hormone appears to regulate receptor-mediated LDL degradation by increasing the binding of the lipoprotein to its cell-surface receptor.", "contents": "Regulatory role of triiodothyronine in the degradation of low density lipoprotein by cultured human skin fibroblasts. Degradation of [125I]-labeled low density lipoprotein (LDL) by cultured normal human skin fibroblasts was enhanced by exposure to concentrations of L-triiodothyronine (T3) spanning the physiological range. Analysis of LDL concentration curves suggests that T3 may increase LDL receptor number rather than alter the affinity of LDL for its receptor. No effect of T3 on LDL degradation was observed in receptor negative cells. Thus thyroid hormone appears to regulate receptor-mediated LDL degradation by increasing the binding of the lipoprotein to its cell-surface receptor."}
{"id": "PMID:219015", "title": "Sensitive solid-phase radioimmunoassay for detection of human immunoglobulin G antibodies to varicella-zoster virus.", "content": "A sensitive solid-phase radioimmunoassay for detection of antibodies to varicella-zoster virus (VZV) is described. The antigen consisted of a sonically disrupted extract of VZV-infected human embryo cells. 125I-labeled rabbit anti-human immunoglobulin G (IgG) specific for the Fc portion of human IgG was used to detect human IgG bound to viral antigen. With this technique, 193 human sera were evaluated for their IgG antibody titer against ZVZ. Subjects included 62 healthy adults, 33 young children (12 healthy), and 49 patients. Titers obtained by the radioimmunoassay were compared with those obtained by indirect fluoresence antibody staining of membrane antigen. The radioimmunoassay technique described gave titers approximately 5 X 10(4) times higher than those shown by indirect fluorescence. It can be used for routine diagnosis, but is especially suited to determining immune status to VZV, as defined by presence or absence of antibodies to the virus; for epidemiological studies; or for determining patients at risk who are exposed to the virus. No heterotypic titer rises to VZV were observed in sera with fourfold or greater rises to Epstein-Barr virus or cytomegalovirus. Sera of eight subjects with fourfold or greater titer rises to herpes simplex virus reacted in various ways: in six cases no significant change occurred in titer to VZV; one had a significant decrease in titer by the radioimmunoassay; and one had a significant increase. Possible reasons for these titer changes are discussed.", "contents": "Sensitive solid-phase radioimmunoassay for detection of human immunoglobulin G antibodies to varicella-zoster virus. A sensitive solid-phase radioimmunoassay for detection of antibodies to varicella-zoster virus (VZV) is described. The antigen consisted of a sonically disrupted extract of VZV-infected human embryo cells. 125I-labeled rabbit anti-human immunoglobulin G (IgG) specific for the Fc portion of human IgG was used to detect human IgG bound to viral antigen. With this technique, 193 human sera were evaluated for their IgG antibody titer against ZVZ. Subjects included 62 healthy adults, 33 young children (12 healthy), and 49 patients. Titers obtained by the radioimmunoassay were compared with those obtained by indirect fluoresence antibody staining of membrane antigen. The radioimmunoassay technique described gave titers approximately 5 X 10(4) times higher than those shown by indirect fluorescence. It can be used for routine diagnosis, but is especially suited to determining immune status to VZV, as defined by presence or absence of antibodies to the virus; for epidemiological studies; or for determining patients at risk who are exposed to the virus. No heterotypic titer rises to VZV were observed in sera with fourfold or greater rises to Epstein-Barr virus or cytomegalovirus. Sera of eight subjects with fourfold or greater titer rises to herpes simplex virus reacted in various ways: in six cases no significant change occurred in titer to VZV; one had a significant decrease in titer by the radioimmunoassay; and one had a significant increase. Possible reasons for these titer changes are discussed."}
{"id": "PMID:219016", "title": "Serodiagnosis of viral hepatitis A by a modified competitive binding radioimmunoassay for immunoglobulin M anti-hepatitis A virus.", "content": "A competitive binding radioimmunoassay (CBA) for antibody to hepatitis A virus (HAV) was evaluated and compared with a standard solid-phase radioimmunoassay for anti-HAV, CBA was found to be sensitive and specific for the detection of anti-HAV, as demonstrated by the 98% concordance of CBA and solid-phase radioimmunoassay test results. The standard CBA test was modified for the differential detection of acute (immunoglobulin M) and convalescent (immunoglobulin G) anti-HAV by incorporation of a step in which immunoglobulin G anti-HAV was preferentially absorbed with S. aureus cells (protein A). The modified CBA test was shown to be capable of differentiating between acute- and convalescent-phase sera. The modified CBAM test was able to detect immunoglobulin M anti-HAV up to approximately 4 weeks after the onset of illness.", "contents": "Serodiagnosis of viral hepatitis A by a modified competitive binding radioimmunoassay for immunoglobulin M anti-hepatitis A virus. A competitive binding radioimmunoassay (CBA) for antibody to hepatitis A virus (HAV) was evaluated and compared with a standard solid-phase radioimmunoassay for anti-HAV, CBA was found to be sensitive and specific for the detection of anti-HAV, as demonstrated by the 98% concordance of CBA and solid-phase radioimmunoassay test results. The standard CBA test was modified for the differential detection of acute (immunoglobulin M) and convalescent (immunoglobulin G) anti-HAV by incorporation of a step in which immunoglobulin G anti-HAV was preferentially absorbed with S. aureus cells (protein A). The modified CBA test was shown to be capable of differentiating between acute- and convalescent-phase sera. The modified CBAM test was able to detect immunoglobulin M anti-HAV up to approximately 4 weeks after the onset of illness."}
{"id": "PMID:219017", "title": "Antibody reactivity to human and vervet cytomegalovirus early antigen(s) in sera from patients with active cytomegalovirus infections and from asymptomatic donors.", "content": "Human fibroblasts were infected with vervet cytomegalovirus (VCMV) and cultured in medium containing 50 micrograms of cytosine arabinoside per ml for 72 h. Early antigens (EAg) were detected in the nuclei of infected cells by an indirect fluorescent antibody test with human sera having antibody to EAg of human cytomegalovirus (HCMV). Sera from patients with serological and/or virological evidence of active HCMV infection and from asymptomatic blood donors were examined for antibody activity with the HCMV and VCMV EAg's. The HCMV and VCMV EAg's were comparable in detecting levels of antibody activity and fluctuations in antibody titer of paired sera from patients. A total of 81% of patient sera reactive with HCMV EAg were also reactive with VCMV EAg. In contrast, only 14% of the asymptomatic donor sera reactive with HCMV EAg were also reactive with VCMV EAg. The VCMV EAg, therefore, appeared to differentiate latent from active infections in humans more effectively than did HCMV EAg.", "contents": "Antibody reactivity to human and vervet cytomegalovirus early antigen(s) in sera from patients with active cytomegalovirus infections and from asymptomatic donors. Human fibroblasts were infected with vervet cytomegalovirus (VCMV) and cultured in medium containing 50 micrograms of cytosine arabinoside per ml for 72 h. Early antigens (EAg) were detected in the nuclei of infected cells by an indirect fluorescent antibody test with human sera having antibody to EAg of human cytomegalovirus (HCMV). Sera from patients with serological and/or virological evidence of active HCMV infection and from asymptomatic blood donors were examined for antibody activity with the HCMV and VCMV EAg's. The HCMV and VCMV EAg's were comparable in detecting levels of antibody activity and fluctuations in antibody titer of paired sera from patients. A total of 81% of patient sera reactive with HCMV EAg were also reactive with VCMV EAg. In contrast, only 14% of the asymptomatic donor sera reactive with HCMV EAg were also reactive with VCMV EAg. The VCMV EAg, therefore, appeared to differentiate latent from active infections in humans more effectively than did HCMV EAg."}
{"id": "PMID:219018", "title": "Comparison of occurrence of antibodies to human cytomegalovirus as demonstrated by immunofluorescence and indirect hemagglutination techniques.", "content": "Indirect immunofluorescence and hemagglutination study of reactivity to human cytomegalovirus immediate early, early, and late antigens revealed that antibody responses to these antigens varies greatly and that hemagglutination is positive when sera contain only antibody to one or both early antigens.", "contents": "Comparison of occurrence of antibodies to human cytomegalovirus as demonstrated by immunofluorescence and indirect hemagglutination techniques. Indirect immunofluorescence and hemagglutination study of reactivity to human cytomegalovirus immediate early, early, and late antigens revealed that antibody responses to these antigens varies greatly and that hemagglutination is positive when sera contain only antibody to one or both early antigens."}
{"id": "PMID:219019", "title": "Feline leukemia virus: survival under home and laboratory conditions.", "content": "Feline leukemia virus maintained its infectiousness in cell culture medium at 37 degrees C or lower for at least 48 h. However, virus in saliva or medium was inactivated within a few hours if allowed to dry.", "contents": "Feline leukemia virus: survival under home and laboratory conditions. Feline leukemia virus maintained its infectiousness in cell culture medium at 37 degrees C or lower for at least 48 h. However, virus in saliva or medium was inactivated within a few hours if allowed to dry."}
{"id": "PMID:219020", "title": "Persistence of antibodies to rotavirus in human milk.", "content": "Human milk obtained from 21 American nursing mothers was studied for the presence of secretory immunoglobulin A antibody to rotavirus, the most common etiological agent of infantile gastroenteritis. Antibody was quantitated by adaptation of a recently described solid-phase radioimmunoassay technique that employs simian rotavirus as a convenient substitute antigen for human rotavirus. Of the mothers tested, 80% (12 of 15) possessed milk antibody within a week of parturition, whereas 56% of those tested (5 of 9) secreted milk antibody as late as 6 or 9 months postpartum. Specificity of the radioimmunoassay was demonstrated by absorption of antibody with purified rotavirus. Our detection by radioimmunoassay of antibody to rotavirus in milk samples collected past the colostrum stage is in contrast to other studies that have failed to detect antibody in human milk by immunofluorescence or neutralization tests. The present study also suggested that the appearance of secretory immunoglobulin A antibody in the milk of mothers previously lacking milk antibody may be correlated with subclinical infection of the mother with rotavirus.", "contents": "Persistence of antibodies to rotavirus in human milk. Human milk obtained from 21 American nursing mothers was studied for the presence of secretory immunoglobulin A antibody to rotavirus, the most common etiological agent of infantile gastroenteritis. Antibody was quantitated by adaptation of a recently described solid-phase radioimmunoassay technique that employs simian rotavirus as a convenient substitute antigen for human rotavirus. Of the mothers tested, 80% (12 of 15) possessed milk antibody within a week of parturition, whereas 56% of those tested (5 of 9) secreted milk antibody as late as 6 or 9 months postpartum. Specificity of the radioimmunoassay was demonstrated by absorption of antibody with purified rotavirus. Our detection by radioimmunoassay of antibody to rotavirus in milk samples collected past the colostrum stage is in contrast to other studies that have failed to detect antibody in human milk by immunofluorescence or neutralization tests. The present study also suggested that the appearance of secretory immunoglobulin A antibody in the milk of mothers previously lacking milk antibody may be correlated with subclinical infection of the mother with rotavirus."}
{"id": "PMID:219021", "title": "Canine kidney cell line for isolation of respiratory viruses.", "content": "By means of a continuous canine kidney cell line (MDCK), influenza viruses were rapidly isolated from specimens collected from patients with respiratory disease. The cell line proved more sensitive than either eggs or rhesus monkey cells for currently circulating influenza A and B strains. Influenza viruses caused a distinct cytopathology within 5 days of inoculation if trypsin-ethylenediamine-tetraacetic acid was incorporated into the medium. Sufficient hemagglutinin was produced on the initial tissue culture passage to allow direct identification of isolates by hemagglutinin inhibition tests. A variety of other respiratory viruses replicated in MDCK, and over a 10-month period 211 of 600 specimens (35%) yielded viruses.", "contents": "Canine kidney cell line for isolation of respiratory viruses. By means of a continuous canine kidney cell line (MDCK), influenza viruses were rapidly isolated from specimens collected from patients with respiratory disease. The cell line proved more sensitive than either eggs or rhesus monkey cells for currently circulating influenza A and B strains. Influenza viruses caused a distinct cytopathology within 5 days of inoculation if trypsin-ethylenediamine-tetraacetic acid was incorporated into the medium. Sufficient hemagglutinin was produced on the initial tissue culture passage to allow direct identification of isolates by hemagglutinin inhibition tests. A variety of other respiratory viruses replicated in MDCK, and over a 10-month period 211 of 600 specimens (35%) yielded viruses."}
{"id": "PMID:219022", "title": "Effect of blood dilution on recovery of organisms from clinical blood cultures in medium containing sodium polyanethol sulfonate.", "content": "This clinical study was designed to evaluate the standard laboratory protocol that requires blood specimens be diluted with greater than or equal to 10 volumes of media. Blood was collected from hospitalized patients, and 1 ml was inoculated into each of three vials containing 2.3, 7.3, and 24 ml of BACTEC 6B aerobic medium resulting in dilutions of 1:4, 1:10, and 1:30, respectively. The three test vials were treated identically, and the study was carried out at four hospitals. Of the 2,550 sets of vials inoculated, 174 were positive with clinically significant isolates from 105 patients. There was no difference in the number of positive cultures recovered by 24 h (67%) or 48 h (90%) from any dilution. These percentages agreed with other reports from BACTEC users. The number of positive vials (139, 144, 147, respectively) at each dilution was not significantly different, indicating that all three dilutions showed equal recovery of pathogenic microorganisms. Despite this overall equality, two patients, one on antibiotic therapy, were found to have correlated cultures which failed to grow at the 1:4 dilution. This finding implies that a 1:4 dilution of blood cannot be recommended unequivocably despite the higher overall recovery rate of positive cultures.", "contents": "Effect of blood dilution on recovery of organisms from clinical blood cultures in medium containing sodium polyanethol sulfonate. This clinical study was designed to evaluate the standard laboratory protocol that requires blood specimens be diluted with greater than or equal to 10 volumes of media. Blood was collected from hospitalized patients, and 1 ml was inoculated into each of three vials containing 2.3, 7.3, and 24 ml of BACTEC 6B aerobic medium resulting in dilutions of 1:4, 1:10, and 1:30, respectively. The three test vials were treated identically, and the study was carried out at four hospitals. Of the 2,550 sets of vials inoculated, 174 were positive with clinically significant isolates from 105 patients. There was no difference in the number of positive cultures recovered by 24 h (67%) or 48 h (90%) from any dilution. These percentages agreed with other reports from BACTEC users. The number of positive vials (139, 144, 147, respectively) at each dilution was not significantly different, indicating that all three dilutions showed equal recovery of pathogenic microorganisms. Despite this overall equality, two patients, one on antibiotic therapy, were found to have correlated cultures which failed to grow at the 1:4 dilution. This finding implies that a 1:4 dilution of blood cannot be recommended unequivocably despite the higher overall recovery rate of positive cultures."}
{"id": "PMID:219023", "title": "Complement-fixing immunoglobulin M antibody response in patients with infantile gastroenteritis.", "content": "Complement-fixing immunoglobulin M antibody to infantile gastroenteritis virus (a rotavirus) was detected with highest sensitivity when the antibody-antigen-complement mixture was incubated at 37 degrees C for 1 h prior to the addition of sensitized sheep erythrocytes. Sucrose gradient centrifugation of sera collected sequentially from four patients after infection detected 19S complement-fixing antibody up to 5 weeks, with highest titers at 1 week, after the onset of illness. Treatment of the whole sera with 2-mercaptoethanol decreased complement-fixing titers only up to 2 weeks after onset of illness.", "contents": "Complement-fixing immunoglobulin M antibody response in patients with infantile gastroenteritis. Complement-fixing immunoglobulin M antibody to infantile gastroenteritis virus (a rotavirus) was detected with highest sensitivity when the antibody-antigen-complement mixture was incubated at 37 degrees C for 1 h prior to the addition of sensitized sheep erythrocytes. Sucrose gradient centrifugation of sera collected sequentially from four patients after infection detected 19S complement-fixing antibody up to 5 weeks, with highest titers at 1 week, after the onset of illness. Treatment of the whole sera with 2-mercaptoethanol decreased complement-fixing titers only up to 2 weeks after onset of illness."}
{"id": "PMID:219024", "title": "Antiherpesvirus activity in human sera and urines after administration of adenine arabinoside: in vitro and in vivo synergy of adenine arabinoside and arabinosylhypoxanthine in combination.", "content": "The minimum inhibitory concentration (MIC) of adenine arabinoside (ara-A) in rabbit kidney microtiter tissue cultures (RK-13) to a prototype strain of herpes simplex virus, type 1 (E115) based upon inhibition of cytopathic effects is 1.5 mug/ml. In this system, the MIC of arabinosylhypoxanthine (ara-Hx), the major in vivo metabolic derivative of ara-A, is 75 mug/ml. Inhibition of cytopathic effects of herpes simplex virus, type 1 (HSV-1) in microtiter wells of RK-13 cells varies directly with the concentrations of ara-A or ara-Hx, and inversely with residual HSV-1. The MIC of ara-A for HSV-1 in RK-13 cells is 5-20 times lower than similar measures with vero renal, mouse embryo, or human foreskin cultures. With RK-13 tissue cultures in microtiter plates, an assay for \"ara-A equivalents\" in human body fluids was developed which compares in sensitivity with high pressure liquid chromatography and has the advantage of simultaneously measuring combined antiherpesvirus effects of ara-A and its major metabolic derivative, ara-Hx. In vitro checkerboard studies in RK-13 cells confirmed that ara-A and ara-Hx in combination had antiviral effects which are synergistic. The total of the fractional MIC of ara-A plus ara-Hx in combination also varies inversely with residual HSV-1 in microtiter wells. Because virus adsorption is complete at 2 h before specimens to be tested are added in this assay, and because human interferon is not measured in rabbit cells, the antiviral assay is not affected by the presence of type-specific antiherpesvirus antibody or human interferon.Antiviral activity (AVA) was assayed as ara-A equivalents in sera and urines from 10 patients with serious herpesvirus infections who received 2.5-20 mg/kg daily of ara-A by intramuscular or intravenous routes. When a dosage schedule of 10 mg/kg per day or more was used, sustained concentrations of AVA that ranged from 0.8 to 14.4 mug/ml were found. When an inhibitor of adenosine deaminase (covidarabine) was not added to the specimens, mean serum concentrations were congruent with3.0 mug/ml (10 mg/kg per day, i.v.), and 4.1 mug/ml (20 mg/kg per day). However, in a single patient given 20 mg/kg of ara-A daily with covidarabine immediately added to the sera, the mean concentration of AVA was 12.9 mug/ml. Urines contained even higher AVA. Assays of 19 sera were performed both by microbiologic assay for AVA and by high pressure liquid chromatography for ara-A and ara-Hx. AVA was greater by microbiologic assay, and was greater than that which could be accounted for by stoichiometric chromatographic measures of ara-A and ara-Hx. These results with sera of treated patients are consistent both with the in vitro synergy of ara-A and ara-Hx found by checkerboard titrations, and with the beneficial responses to ara-A of patients with herpesvirus infections reported here and elsewhere.", "contents": "Antiherpesvirus activity in human sera and urines after administration of adenine arabinoside: in vitro and in vivo synergy of adenine arabinoside and arabinosylhypoxanthine in combination. The minimum inhibitory concentration (MIC) of adenine arabinoside (ara-A) in rabbit kidney microtiter tissue cultures (RK-13) to a prototype strain of herpes simplex virus, type 1 (E115) based upon inhibition of cytopathic effects is 1.5 mug/ml. In this system, the MIC of arabinosylhypoxanthine (ara-Hx), the major in vivo metabolic derivative of ara-A, is 75 mug/ml. Inhibition of cytopathic effects of herpes simplex virus, type 1 (HSV-1) in microtiter wells of RK-13 cells varies directly with the concentrations of ara-A or ara-Hx, and inversely with residual HSV-1. The MIC of ara-A for HSV-1 in RK-13 cells is 5-20 times lower than similar measures with vero renal, mouse embryo, or human foreskin cultures. With RK-13 tissue cultures in microtiter plates, an assay for \"ara-A equivalents\" in human body fluids was developed which compares in sensitivity with high pressure liquid chromatography and has the advantage of simultaneously measuring combined antiherpesvirus effects of ara-A and its major metabolic derivative, ara-Hx. In vitro checkerboard studies in RK-13 cells confirmed that ara-A and ara-Hx in combination had antiviral effects which are synergistic. The total of the fractional MIC of ara-A plus ara-Hx in combination also varies inversely with residual HSV-1 in microtiter wells. Because virus adsorption is complete at 2 h before specimens to be tested are added in this assay, and because human interferon is not measured in rabbit cells, the antiviral assay is not affected by the presence of type-specific antiherpesvirus antibody or human interferon.Antiviral activity (AVA) was assayed as ara-A equivalents in sera and urines from 10 patients with serious herpesvirus infections who received 2.5-20 mg/kg daily of ara-A by intramuscular or intravenous routes. When a dosage schedule of 10 mg/kg per day or more was used, sustained concentrations of AVA that ranged from 0.8 to 14.4 mug/ml were found. When an inhibitor of adenosine deaminase (covidarabine) was not added to the specimens, mean serum concentrations were congruent with3.0 mug/ml (10 mg/kg per day, i.v.), and 4.1 mug/ml (20 mg/kg per day). However, in a single patient given 20 mg/kg of ara-A daily with covidarabine immediately added to the sera, the mean concentration of AVA was 12.9 mug/ml. Urines contained even higher AVA. Assays of 19 sera were performed both by microbiologic assay for AVA and by high pressure liquid chromatography for ara-A and ara-Hx. AVA was greater by microbiologic assay, and was greater than that which could be accounted for by stoichiometric chromatographic measures of ara-A and ara-Hx. These results with sera of treated patients are consistent both with the in vitro synergy of ara-A and ara-Hx found by checkerboard titrations, and with the beneficial responses to ara-A of patients with herpesvirus infections reported here and elsewhere."}
{"id": "PMID:219025", "title": "Effects of osmolality and oxygen availability on soluble cyclic AMP-dependent protein kinase activity of rat renal inner medulla.", "content": "The renal inner medulla is ordinarily exposed to osmolalities that are much higher and to O2 tensions that are lower than those in other tissues. The effects of media osmolality and O2 availability on basal and arginine vasopressin(AVP)-responsive soluble cyclic (c)AMP-dependent protein kinase activity were examined in slices of rat inner medulla. Increasing total media osmolality from 305 to 750 or 1,650 mosM by addition of urea plas NaCl to standard Krebs-Ringer bicarbonate buffer significantly reduced basal cAMP content and protein kinase activity ratios. This occurred in the presence or absence of O2. Incubation of slices in high osmolality buffer also blunted increases in inner medullary slice cAMP and protein kinase activity ratios induced by O2. These changes reflected predominantly an action of the urea rather than the NaCl content of high osmolality buffers. In contrast to effects on basal activity, high media osmolality significantly enhanced activation of inner medullary protein kinase by AVP. Conversely, increases in media O2 content suppressed AVP stimulation of enzyme activity. This inhibitory effect of O2 was best expressed at low osmolality. Naproxen and ibuprofen, inhibitors of prostaglandin biosynthesis, reduced basal kinase activity ratios and increased AVP responsiveness in the presence, but not in the absence, of O2. Exogenous prostaglandins (PG) modestly increased (PGE2 and PGE1) or did not change (PGF2alpha) cAMP and protein kinase activity ratios in O2-deprived inner medullary slices. Protein kinase activation by PGE2 was not observed in oxygenated inner medulla with high basal activity ratios. The stimulatory effects of PGE2 and PGE1 on protein kinase activity observed in O2-deprived slices were additive with those of submaximal or maximal AVP. PGE2, PGE1, and PGF2alpha all failed to suppress AVP activation of protein kinase. Thus, enhanced endogenous PGE production may contribute to the higher basal protein kinase activity ratios induced by O2. However, the results do not support a role for PGE2, PGE1, or PGF2alpha in O2-mediated inhibition of AVP responsiveness. The present data indicate that both solute content and O2 availability can alter the expression of AVP action on cAMP-dependent protein kinase activity in inner medulla. AVP activation of protein kinase is best expressed when osmolality is high and O2 availability is low, conditions that pertain in inner medulla during hydropenia.", "contents": "Effects of osmolality and oxygen availability on soluble cyclic AMP-dependent protein kinase activity of rat renal inner medulla. The renal inner medulla is ordinarily exposed to osmolalities that are much higher and to O2 tensions that are lower than those in other tissues. The effects of media osmolality and O2 availability on basal and arginine vasopressin(AVP)-responsive soluble cyclic (c)AMP-dependent protein kinase activity were examined in slices of rat inner medulla. Increasing total media osmolality from 305 to 750 or 1,650 mosM by addition of urea plas NaCl to standard Krebs-Ringer bicarbonate buffer significantly reduced basal cAMP content and protein kinase activity ratios. This occurred in the presence or absence of O2. Incubation of slices in high osmolality buffer also blunted increases in inner medullary slice cAMP and protein kinase activity ratios induced by O2. These changes reflected predominantly an action of the urea rather than the NaCl content of high osmolality buffers. In contrast to effects on basal activity, high media osmolality significantly enhanced activation of inner medullary protein kinase by AVP. Conversely, increases in media O2 content suppressed AVP stimulation of enzyme activity. This inhibitory effect of O2 was best expressed at low osmolality. Naproxen and ibuprofen, inhibitors of prostaglandin biosynthesis, reduced basal kinase activity ratios and increased AVP responsiveness in the presence, but not in the absence, of O2. Exogenous prostaglandins (PG) modestly increased (PGE2 and PGE1) or did not change (PGF2alpha) cAMP and protein kinase activity ratios in O2-deprived inner medullary slices. Protein kinase activation by PGE2 was not observed in oxygenated inner medulla with high basal activity ratios. The stimulatory effects of PGE2 and PGE1 on protein kinase activity observed in O2-deprived slices were additive with those of submaximal or maximal AVP. PGE2, PGE1, and PGF2alpha all failed to suppress AVP activation of protein kinase. Thus, enhanced endogenous PGE production may contribute to the higher basal protein kinase activity ratios induced by O2. However, the results do not support a role for PGE2, PGE1, or PGF2alpha in O2-mediated inhibition of AVP responsiveness. The present data indicate that both solute content and O2 availability can alter the expression of AVP action on cAMP-dependent protein kinase activity in inner medulla. AVP activation of protein kinase is best expressed when osmolality is high and O2 availability is low, conditions that pertain in inner medulla during hydropenia."}
{"id": "PMID:219026", "title": "Altered activity of the nucleotide regulatory site in the parathyroid hormone-sensitive adenylate cyclase from the renal cortex of a patient with pseudohypoparathyroidism.", "content": "A series of clinical studies suggest that the primary defect underlying pseudohypoparathyroidism is an abnormality of the parathyroid hormone-receptor-adenylate cyclase complex of the renal cortical cell plasma membrane. In the present study we compared parathyroid hormone-stimulated adenylate cyclase activity in membrane preparations from the renal cortex of three controls and a patient with pseudohypoparathyroidism. In the pseudohypoparathyroid preparation the Km for ATP was significantly greater and parathyroid hormone elicited markedly diminished adenylate cyclase activity at a subsaturating concentration of ATP. In contrast, the dose-response effect of enzyme activity to parathyroid hormone was the same in the control preparations, and that of the pseudohypoparathyroidism kidney, at a saturating concentration of ATP. The apparent alteration in enzyme kinetics, however, was normalized upon addition of guanosine 5'-triphosphate to the reaction mixtures. These results indicate that the defect in the parathyroid hormone-receptor-adenylate cyclase complex of the renal cell membranes, in our patient with pseudohypoparathyroidism, is an abnormal nucleotide receptor site of decreased activity. Such a defect may result in partial uncoupling of the parathyroid hormone receptor and adenylate cyclase, rendering the organ refractory to hormonal stimulation.", "contents": "Altered activity of the nucleotide regulatory site in the parathyroid hormone-sensitive adenylate cyclase from the renal cortex of a patient with pseudohypoparathyroidism. A series of clinical studies suggest that the primary defect underlying pseudohypoparathyroidism is an abnormality of the parathyroid hormone-receptor-adenylate cyclase complex of the renal cortical cell plasma membrane. In the present study we compared parathyroid hormone-stimulated adenylate cyclase activity in membrane preparations from the renal cortex of three controls and a patient with pseudohypoparathyroidism. In the pseudohypoparathyroid preparation the Km for ATP was significantly greater and parathyroid hormone elicited markedly diminished adenylate cyclase activity at a subsaturating concentration of ATP. In contrast, the dose-response effect of enzyme activity to parathyroid hormone was the same in the control preparations, and that of the pseudohypoparathyroidism kidney, at a saturating concentration of ATP. The apparent alteration in enzyme kinetics, however, was normalized upon addition of guanosine 5'-triphosphate to the reaction mixtures. These results indicate that the defect in the parathyroid hormone-receptor-adenylate cyclase complex of the renal cell membranes, in our patient with pseudohypoparathyroidism, is an abnormal nucleotide receptor site of decreased activity. Such a defect may result in partial uncoupling of the parathyroid hormone receptor and adenylate cyclase, rendering the organ refractory to hormonal stimulation."}
{"id": "PMID:219027", "title": "Viral infection-homograft interactions in a murine model.", "content": "The effects on some host defenses of murine cytomegalovirus (MCMV) and(or) EL(4), a mouse ascites homograft, were studied in mice. Assays of cellular and humoral immunity in response to either or both of these perturbations were carried out by quantitation of various immune activities.Limited studies demonstrated no effect of EL(4) inoculation on the host response to MCMV by organ viral titer, duration of viral persistence, or anti MCMV complement-fixing antibody titer. Prior infection with MCMV, however, resulted in greatly reduced numbers of splenocytes, the source in this study of immune effector cells. Residual splenocytes demonstrated less response to both phyto-hemagglutinin and lipopolysaccharide, particularly in the 2-3-wk interval after infection. Similarly, responder cells in mixed lymphocyte cultures were less reactive when derived from infected animals. Lymphocyte-mediated cytolysis of EL(4) was significantly less in mice infected on the day of and 7, 14, and 21 days before the tumor homograft with a return to control levels by 28 days. 90% of the cell-mediated cytolysis could be eliminated by treatment with anti-theta serum. Serum-mediated cytolysis of EL(4) was also reduced in infected animals. No suppressor cells or serum inhibitory factors could be identified in infected animals. Although alternative explanations exist, this study suggests that in infected animals there is a significant reduction in both the number and function of bone marrow-derived and thymus-derived cells directed against the alloantigens in EL(4).", "contents": "Viral infection-homograft interactions in a murine model. The effects on some host defenses of murine cytomegalovirus (MCMV) and(or) EL(4), a mouse ascites homograft, were studied in mice. Assays of cellular and humoral immunity in response to either or both of these perturbations were carried out by quantitation of various immune activities.Limited studies demonstrated no effect of EL(4) inoculation on the host response to MCMV by organ viral titer, duration of viral persistence, or anti MCMV complement-fixing antibody titer. Prior infection with MCMV, however, resulted in greatly reduced numbers of splenocytes, the source in this study of immune effector cells. Residual splenocytes demonstrated less response to both phyto-hemagglutinin and lipopolysaccharide, particularly in the 2-3-wk interval after infection. Similarly, responder cells in mixed lymphocyte cultures were less reactive when derived from infected animals. Lymphocyte-mediated cytolysis of EL(4) was significantly less in mice infected on the day of and 7, 14, and 21 days before the tumor homograft with a return to control levels by 28 days. 90% of the cell-mediated cytolysis could be eliminated by treatment with anti-theta serum. Serum-mediated cytolysis of EL(4) was also reduced in infected animals. No suppressor cells or serum inhibitory factors could be identified in infected animals. Although alternative explanations exist, this study suggests that in infected animals there is a significant reduction in both the number and function of bone marrow-derived and thymus-derived cells directed against the alloantigens in EL(4)."}
{"id": "PMID:219028", "title": "Modulation of cyclic nucleotides in islated rat glomeruli: role of histamine, carbamylcholine, parathyroid hormone, and angiotensin-II.", "content": "Because glomerular functions are modulated by numerous humoral agents, probably acting through cyclic nucleotides, the effects of some polypeptide hormones and biogenic amines on cyclic AMP (cAMP) and cyclic 3',5'-guanosine monophosphate (cGMP) were studied in glomeruli isolated from rat renal cortex. Glomeruli and cortical tubules were prepared by a combination of sieving and density-gradient centrifugation. Under basal conditions, the contents of cAMP and cGMP in glomeruli were significantly higher than in tubules and unfractionated renal cortical tissue.Histamine caused a striking increase in cAMP in glomeruli (+Delta% 675+/-87) and, to a lesser degree, increased cAMP in tubules (+Delta% 103+/-25) or in tissue slices. This stimulation was dose-dependent in the range of 1 muM-1 mM histamine. Metiamide (an H(2)-antagonist), but not pyrilamine (an H(1)-antagonist) blocked the effect of histamine on cAMP, which indicates that histamine causes its effect via interaction with H(2) receptors. Histamine caused less extensive increases in cGMP in both glomeruli and tubules. Carbamylcholine caused a marked increase in cGMP in glomeruli (+Delta 295+/-7) and a much lower increase in tubules (+Delta% 70+/-20); these effects were blocked by atropine. Parathyroid hormone (1 mug/ml) increased cAMP and, to a much lesser degree, also cGMP in glomeruli. In tubules, parathyroid hormone caused much more extensive increases in cAMP than in glomeruli; no changes, or rather a small decline in cGMP, was observed. Angiotensin-II (2 muM) markedly lowered cAMP in glomeruli (-Delta% -45+/-8) and in tubules (-Delta% 33+/-7) but had no effect on cGMP. Bradykinin (20 muM) did not consistently influence either cAMP or cGMP in glomeruli or tubules. Present results demonstrate that cAMP and cGMP metabolism in glomeruli are controlled independently by humoral agents known to alter glomerular functions in vivo. Our findings are consistent with the view that histamine and cholinergic agents generated and (or) released locally in glomeruli or in their vicinity may play important roles as mediators of immunopathological injury of glomeruli, and that these effects are mediated by cAMP and (or) cGMP through interaction with H(2) receptors and muscarinic receptors. Likewise, our results suggest that the effects of angiotensin-II and parathyroid hormone on glomerular dynamics may be mediated by cyclic nucleotides.Thus, we surmise that extrarenal as well as intrarenal humoral agents may play an important role in the pathology and physiology of glomeruli through mediation of either cAMP, cGMP, or both.", "contents": "Modulation of cyclic nucleotides in islated rat glomeruli: role of histamine, carbamylcholine, parathyroid hormone, and angiotensin-II. Because glomerular functions are modulated by numerous humoral agents, probably acting through cyclic nucleotides, the effects of some polypeptide hormones and biogenic amines on cyclic AMP (cAMP) and cyclic 3',5'-guanosine monophosphate (cGMP) were studied in glomeruli isolated from rat renal cortex. Glomeruli and cortical tubules were prepared by a combination of sieving and density-gradient centrifugation. Under basal conditions, the contents of cAMP and cGMP in glomeruli were significantly higher than in tubules and unfractionated renal cortical tissue.Histamine caused a striking increase in cAMP in glomeruli (+Delta% 675+/-87) and, to a lesser degree, increased cAMP in tubules (+Delta% 103+/-25) or in tissue slices. This stimulation was dose-dependent in the range of 1 muM-1 mM histamine. Metiamide (an H(2)-antagonist), but not pyrilamine (an H(1)-antagonist) blocked the effect of histamine on cAMP, which indicates that histamine causes its effect via interaction with H(2) receptors. Histamine caused less extensive increases in cGMP in both glomeruli and tubules. Carbamylcholine caused a marked increase in cGMP in glomeruli (+Delta 295+/-7) and a much lower increase in tubules (+Delta% 70+/-20); these effects were blocked by atropine. Parathyroid hormone (1 mug/ml) increased cAMP and, to a much lesser degree, also cGMP in glomeruli. In tubules, parathyroid hormone caused much more extensive increases in cAMP than in glomeruli; no changes, or rather a small decline in cGMP, was observed. Angiotensin-II (2 muM) markedly lowered cAMP in glomeruli (-Delta% -45+/-8) and in tubules (-Delta% 33+/-7) but had no effect on cGMP. Bradykinin (20 muM) did not consistently influence either cAMP or cGMP in glomeruli or tubules. Present results demonstrate that cAMP and cGMP metabolism in glomeruli are controlled independently by humoral agents known to alter glomerular functions in vivo. Our findings are consistent with the view that histamine and cholinergic agents generated and (or) released locally in glomeruli or in their vicinity may play important roles as mediators of immunopathological injury of glomeruli, and that these effects are mediated by cAMP and (or) cGMP through interaction with H(2) receptors and muscarinic receptors. Likewise, our results suggest that the effects of angiotensin-II and parathyroid hormone on glomerular dynamics may be mediated by cyclic nucleotides.Thus, we surmise that extrarenal as well as intrarenal humoral agents may play an important role in the pathology and physiology of glomeruli through mediation of either cAMP, cGMP, or both."}
{"id": "PMID:219029", "title": "Studies on the structure of low density lipoproteins isolated from Macaca fascicularis fed an atherogenic diet.", "content": "Cynomolgus monkeys, Macaca fascicularis, fed cholesterol-containing saturated-fat diets develop increased levels of high molecular weight plasma low density lipoproteins (LDL), associated with accelerated atherosclerosis. To study the composition and structure of these abnormal particles, LDL from monkeys, fed atherogenic and control diets, were characterized chemically and examined by differential scanning calorimetry and low-angle X-ray scattering. LDL from animals on the experimental diet showed an increase in molecular weight (4.0 to 7.0 x 10(6), experimental diet compared with 3.0 to 3.7 x 10(6), control diet) associated with a large increase in cholesterol ester content and concomitant smaller increases in protein, phospholipid, and free cholesterol. There was a strong positive correlation between molecular weight and the number of saturated and monounsaturated cholesterol esters in the particle. In contrast, particle content of polyunsaturated cholesterol esters remained constant despite large changes in total particle cholesterol esters.When examined by calorimetry and X-ray scattering, LDL from monkeys on both diets diplayed a reversible transition of cholesterol esters from an ordered smeticlike (layered) structure to a more disordered state. For all animals on the experimental diet, the peak temperature of the cholesterol-ester transition (42-48 degrees C) was above body temperature (39 degrees C), but below body temperature on the control diet (34-38.5 degrees C). In the experimental group, the transition temperature was correlated with the LDL molecular weight. However, after thermal disruption of LDL, liquid-crystalline transitions of LDL cholesterol esters were observed in the same temperature range as in the intact lipoprotein, which shows that changes in particle size had little effect on the cholesterol-ester transition temperature. Rather, the transition temperature was determined by the degree of saturation of the LDL cholesterol ester fatty acids and the LDL cholesterol ester: triglyceride ratio, both of which correlated with increased LDL molecular weight.The existence of smectic-like cholesterol ester in LDL at body temperature was clearly a discriminating feature between monkeys on control and experimental diets. Diet-induced changes in the lipid composition of precursor lipoproteins of LDL appeared to lead to the existence of smectic-like cholesterol ester in LDL above body temperature. The altered composition and structure of the core lipids of high molecular weight LDL probably account, in part, for the previously documented correlation between increased LDL molecular weight and atherosclerosis in this species.", "contents": "Studies on the structure of low density lipoproteins isolated from Macaca fascicularis fed an atherogenic diet. Cynomolgus monkeys, Macaca fascicularis, fed cholesterol-containing saturated-fat diets develop increased levels of high molecular weight plasma low density lipoproteins (LDL), associated with accelerated atherosclerosis. To study the composition and structure of these abnormal particles, LDL from monkeys, fed atherogenic and control diets, were characterized chemically and examined by differential scanning calorimetry and low-angle X-ray scattering. LDL from animals on the experimental diet showed an increase in molecular weight (4.0 to 7.0 x 10(6), experimental diet compared with 3.0 to 3.7 x 10(6), control diet) associated with a large increase in cholesterol ester content and concomitant smaller increases in protein, phospholipid, and free cholesterol. There was a strong positive correlation between molecular weight and the number of saturated and monounsaturated cholesterol esters in the particle. In contrast, particle content of polyunsaturated cholesterol esters remained constant despite large changes in total particle cholesterol esters.When examined by calorimetry and X-ray scattering, LDL from monkeys on both diets diplayed a reversible transition of cholesterol esters from an ordered smeticlike (layered) structure to a more disordered state. For all animals on the experimental diet, the peak temperature of the cholesterol-ester transition (42-48 degrees C) was above body temperature (39 degrees C), but below body temperature on the control diet (34-38.5 degrees C). In the experimental group, the transition temperature was correlated with the LDL molecular weight. However, after thermal disruption of LDL, liquid-crystalline transitions of LDL cholesterol esters were observed in the same temperature range as in the intact lipoprotein, which shows that changes in particle size had little effect on the cholesterol-ester transition temperature. Rather, the transition temperature was determined by the degree of saturation of the LDL cholesterol ester fatty acids and the LDL cholesterol ester: triglyceride ratio, both of which correlated with increased LDL molecular weight.The existence of smectic-like cholesterol ester in LDL at body temperature was clearly a discriminating feature between monkeys on control and experimental diets. Diet-induced changes in the lipid composition of precursor lipoproteins of LDL appeared to lead to the existence of smectic-like cholesterol ester in LDL above body temperature. The altered composition and structure of the core lipids of high molecular weight LDL probably account, in part, for the previously documented correlation between increased LDL molecular weight and atherosclerosis in this species."}
{"id": "PMID:219030", "title": "Presence of immunoreactive beta-endorphin in normal human plasma: a concomitant release of beta-endorphin with adrenocorticotropin after metyrapone administration.", "content": "To elucidate whether or not beta-endorphin exists in plasma of normal subjects, plasma extracts obtained before and after metyrapone administration were subjected to gel exclusion chromatography, and fractions obtained were assayed by a sensitive radioimmunoassay for beta-endorphin. The basal plasma level of beta-endorphin was 5.8 +/- 1.1 pg/ml (mean +/- SE, n = 5), which rose significantly to the level of 48.9 +/- 3.8 pg/ml after a single oral dose (30 mg/kg of body wt) of metyrapone administration (P less than 0.001). Plasma ACTH levels also increased from the mean basal level of 73 +/- 4 pg/ml to 269 +/- 41 pg/ml after metyrapone administration. These results indicate that beta-endorphin, distinct from beta-lipotropin, exists in normal human plasma and that it is released from the pituitary concomitantly with ACTH.", "contents": "Presence of immunoreactive beta-endorphin in normal human plasma: a concomitant release of beta-endorphin with adrenocorticotropin after metyrapone administration. To elucidate whether or not beta-endorphin exists in plasma of normal subjects, plasma extracts obtained before and after metyrapone administration were subjected to gel exclusion chromatography, and fractions obtained were assayed by a sensitive radioimmunoassay for beta-endorphin. The basal plasma level of beta-endorphin was 5.8 +/- 1.1 pg/ml (mean +/- SE, n = 5), which rose significantly to the level of 48.9 +/- 3.8 pg/ml after a single oral dose (30 mg/kg of body wt) of metyrapone administration (P less than 0.001). Plasma ACTH levels also increased from the mean basal level of 73 +/- 4 pg/ml to 269 +/- 41 pg/ml after metyrapone administration. These results indicate that beta-endorphin, distinct from beta-lipotropin, exists in normal human plasma and that it is released from the pituitary concomitantly with ACTH."}
{"id": "PMID:219031", "title": "Myeloperoxidase-mediated platelet release reaction.", "content": "The ability of the neutrophil myeloperoxidase-hydrogen peroxide-halide system to induce the release of human platelet constituents was examined. Both lytic and nonlytic effects on platelets were assessed by comparison of the simultaneously measured release of a dense-granule marker, [(3)H]serotonin, and a cytoplasmic marker, [(14)C]adenine. Incubation of platelets with H(2)O(2) alone (20 muM H(2)O(2) for 10 min) resulted in a small, although significant, release of both serotonin and adenine, suggesting some platelet lysis. Substantial release of these markers was observed only with increased H(2)O(2) concentrations (>0.1 mM) or prolonged incubation (1-2 h). Serotonin release by H(2)O(2) was markedly enhanced by the addition of myeloperoxidase and a halide. Under these conditions, there was a predominance of release of serotonin (50%) vs. adenine (13%), suggesting, in part, a nonlytic mechanism. Serotonin release by the complete peroxidase system was rapid, reaching maximal levels in 2-5 min, and was active at H(2)O(2) concentrations as low as 10 muM. It was blocked by agents which inhibit peroxidase (azide, cyanide), degrade H(2)O(2) (catalase), chelate Mg(2+) (EDTA, but not EGTA), or inhibit platelet metabolic activity (dinitrophenol, deoxyglucose).These results suggest that the myeloperoxidase system initiates the release of platelet constituents primarily by a nonlytic process analogous to the platelet release reaction. Because components of the peroxidase system (myeloperoxidase, H(2)O(2)) are secreted by activated neutrophils, the reactions described here may have implications for neutrophilplatelet interaction in sites of thrombus formation.", "contents": "Myeloperoxidase-mediated platelet release reaction. The ability of the neutrophil myeloperoxidase-hydrogen peroxide-halide system to induce the release of human platelet constituents was examined. Both lytic and nonlytic effects on platelets were assessed by comparison of the simultaneously measured release of a dense-granule marker, [(3)H]serotonin, and a cytoplasmic marker, [(14)C]adenine. Incubation of platelets with H(2)O(2) alone (20 muM H(2)O(2) for 10 min) resulted in a small, although significant, release of both serotonin and adenine, suggesting some platelet lysis. Substantial release of these markers was observed only with increased H(2)O(2) concentrations (>0.1 mM) or prolonged incubation (1-2 h). Serotonin release by H(2)O(2) was markedly enhanced by the addition of myeloperoxidase and a halide. Under these conditions, there was a predominance of release of serotonin (50%) vs. adenine (13%), suggesting, in part, a nonlytic mechanism. Serotonin release by the complete peroxidase system was rapid, reaching maximal levels in 2-5 min, and was active at H(2)O(2) concentrations as low as 10 muM. It was blocked by agents which inhibit peroxidase (azide, cyanide), degrade H(2)O(2) (catalase), chelate Mg(2+) (EDTA, but not EGTA), or inhibit platelet metabolic activity (dinitrophenol, deoxyglucose).These results suggest that the myeloperoxidase system initiates the release of platelet constituents primarily by a nonlytic process analogous to the platelet release reaction. Because components of the peroxidase system (myeloperoxidase, H(2)O(2)) are secreted by activated neutrophils, the reactions described here may have implications for neutrophilplatelet interaction in sites of thrombus formation."}
{"id": "PMID:219032", "title": "The influence of hyperthyroidism and hypothyroidism on the beta-adrenergic responsiveness of the turkey erythrocyte.", "content": "The mechanisms responsible for altered adrenergic tone in hyperthyroidism and hypothyroidism are not fully understood. To investigate these mechanisms, the beta-adrenergic receptor-cyclic AMP complex of the turkey erythrocyte was studied among groups of normal, hyperthyroid, and hypothyroid turkeys. In erythrocytes obtained from hypothyroid turkeys, there were fewer beta-adrenergic receptors than in normal cells as determined by the specific binding of [(125)I]iodohydroxybenzylpindolol, as well as associated decreases both in catecholamine-responsive adenylate cyclase activity and in cellular cyclic AMP content. In contrast, erythrocytes obtained from hyperthyroid turkeys contained the same number of beta-receptors and had the same catecholamine-responsive adenylate cyclase activity as cells from normal birds. Other characteristics of the beta-receptors in cells from hyperthyroid birds were indistinguishable from those present in normal erythrocytes. However, within the range of circulating catecholamine concentrations, 5-50 nM, the erythrocytes of the hyperthyroid turkeys generated substantially more cyclic AMP after exposure to isoproterenol than did normal cells. These results suggest that thyroid hormone affects beta-receptor-cyclic AMP interrelationships in the turkey erythrocyte by two distinct mechanisms: (a) In hypothyroidism, both beta-receptors and catecholamine-dependent cyclic AMP formation are coordinately decreased; (b) in hyperthyroidism, beta-receptors are unchanged but there is an amplification of the hormonal signal so that occupation of a given number of receptors at physiological concentrations of catecholamines leads to increased levels of cyclic AMP.", "contents": "The influence of hyperthyroidism and hypothyroidism on the beta-adrenergic responsiveness of the turkey erythrocyte. The mechanisms responsible for altered adrenergic tone in hyperthyroidism and hypothyroidism are not fully understood. To investigate these mechanisms, the beta-adrenergic receptor-cyclic AMP complex of the turkey erythrocyte was studied among groups of normal, hyperthyroid, and hypothyroid turkeys. In erythrocytes obtained from hypothyroid turkeys, there were fewer beta-adrenergic receptors than in normal cells as determined by the specific binding of [(125)I]iodohydroxybenzylpindolol, as well as associated decreases both in catecholamine-responsive adenylate cyclase activity and in cellular cyclic AMP content. In contrast, erythrocytes obtained from hyperthyroid turkeys contained the same number of beta-receptors and had the same catecholamine-responsive adenylate cyclase activity as cells from normal birds. Other characteristics of the beta-receptors in cells from hyperthyroid birds were indistinguishable from those present in normal erythrocytes. However, within the range of circulating catecholamine concentrations, 5-50 nM, the erythrocytes of the hyperthyroid turkeys generated substantially more cyclic AMP after exposure to isoproterenol than did normal cells. These results suggest that thyroid hormone affects beta-receptor-cyclic AMP interrelationships in the turkey erythrocyte by two distinct mechanisms: (a) In hypothyroidism, both beta-receptors and catecholamine-dependent cyclic AMP formation are coordinately decreased; (b) in hyperthyroidism, beta-receptors are unchanged but there is an amplification of the hormonal signal so that occupation of a given number of receptors at physiological concentrations of catecholamines leads to increased levels of cyclic AMP."}
{"id": "PMID:219033", "title": "Differential sensitivity of lymphocyte subpopulations to suppression by low density lipoprotein inhibitor, an immunoregulatory human serum low density lipoprotein.", "content": "Reports by a number of investigators have described the thymus-derived (T)-cell dependence of immunoglobulin synthesis by pokeweed mitogen (PWM) stimulated human peripheral blood bone marrow-derived (B) cells. Because of the cooperative nature of this in vitro system, it was chosen for examination of the differential effects of low density lipoprotein inhibitor (LDL-In) on B- and T-cell functions. Supernates from 7-d cultures that contained either peripheral blood mononuclear cells (PBM) or combinations of isolated lymphocyte populations were assayed for immunoglobulin (Ig)G by competitive inhibition radio-immunoassay. LDL-In suppression of whole PBM IgG synthesis occurred at 5-20 mug protein/ml and was independent of PWM concentration. Maximal suppression required preincubation of cells with LDL-In before stimulation. Suppression was also observed when B cells alone were exposed for 24 h to LDL-In before PWM stimulation; these suppressed B cells were not rescued by normal T cells. Exposure of T cells alone to low doses of LDL-In for 24 h augmented, but high doses suppressed, IgG synthesis, suggesting a differential effect on T-helper vs T-suppressor cell populations. Independent LDL-In exposure of T-helper or T-suppressor cell enriched populations, separated by rosetting with IgG- or IgM-coated ox erythrocytes, identified the T-suppressor cell populations as the most sensitive of the lymphocyte populations tested. The sensitivities of lymphocyte subpopulations to LDL-In, relative to PBM, were 2.8, 1.2, and 0.3 for the T-suppressor cells, B cells and T-helper cells, respectively. Thus, both B and T lymphocytes are sensitive to and can be regulated by LDL-In. In addition, the biologic activity observed when unseparated PBM are exposed to LDL-In appears to represent a composite of the sensitivity of each of the lymphocyte subpopulations.", "contents": "Differential sensitivity of lymphocyte subpopulations to suppression by low density lipoprotein inhibitor, an immunoregulatory human serum low density lipoprotein. Reports by a number of investigators have described the thymus-derived (T)-cell dependence of immunoglobulin synthesis by pokeweed mitogen (PWM) stimulated human peripheral blood bone marrow-derived (B) cells. Because of the cooperative nature of this in vitro system, it was chosen for examination of the differential effects of low density lipoprotein inhibitor (LDL-In) on B- and T-cell functions. Supernates from 7-d cultures that contained either peripheral blood mononuclear cells (PBM) or combinations of isolated lymphocyte populations were assayed for immunoglobulin (Ig)G by competitive inhibition radio-immunoassay. LDL-In suppression of whole PBM IgG synthesis occurred at 5-20 mug protein/ml and was independent of PWM concentration. Maximal suppression required preincubation of cells with LDL-In before stimulation. Suppression was also observed when B cells alone were exposed for 24 h to LDL-In before PWM stimulation; these suppressed B cells were not rescued by normal T cells. Exposure of T cells alone to low doses of LDL-In for 24 h augmented, but high doses suppressed, IgG synthesis, suggesting a differential effect on T-helper vs T-suppressor cell populations. Independent LDL-In exposure of T-helper or T-suppressor cell enriched populations, separated by rosetting with IgG- or IgM-coated ox erythrocytes, identified the T-suppressor cell populations as the most sensitive of the lymphocyte populations tested. The sensitivities of lymphocyte subpopulations to LDL-In, relative to PBM, were 2.8, 1.2, and 0.3 for the T-suppressor cells, B cells and T-helper cells, respectively. Thus, both B and T lymphocytes are sensitive to and can be regulated by LDL-In. In addition, the biologic activity observed when unseparated PBM are exposed to LDL-In appears to represent a composite of the sensitivity of each of the lymphocyte subpopulations."}
{"id": "PMID:219034", "title": "Differential and integral corticosteroid feedback effects on ACTH secretion in hypoadrenocorticism.", "content": "Recent work suggests the existence of a dual corticosteroid feedback mechanism of stress-induced ACTH secretion in the rat. This possibility led us to study the kinetics of suppression of ACTH levels by corticosteroid administration in patients with nonstress ACTH hypersecretion secondary to hypoadrenocorticism. Cortisol was administered according to different protocols, which were chosen to provide extreme variations of the input signal. By this means, two phases of suppression of ACTH levels could be differentiated. A first decrease occurred without latency whenever, and as long as, plasma cortisol levels were rising. There was a linear regression between the logarithm of the increments in cortisol concentrations and the decrease in ACTH levels per minute (r = 0.951) (differential or rate-sensitive feedback mechanism). Neither the absolute doses of cortisol, nor plasma cortisol concentrations were closely correlated with the degree of suppression of ACTH by this rapid mechanism. A second decrease in ACTH levels began congruent with30 min after corticosteroid administration. In this case there was a significant linear regression between the degree of inhibition of ACTH levels and the cortisol doses (r = 0.997) (integral or dose-sensitive feedback mechanism). The dose-sensitive feedback effects of dexamethasone were less than might have been predicted from its relative anti-inflammatory potency. No rate-sensitive effects were seen with dexamethasone doses of 1.0 or 1.25 mg.", "contents": "Differential and integral corticosteroid feedback effects on ACTH secretion in hypoadrenocorticism. Recent work suggests the existence of a dual corticosteroid feedback mechanism of stress-induced ACTH secretion in the rat. This possibility led us to study the kinetics of suppression of ACTH levels by corticosteroid administration in patients with nonstress ACTH hypersecretion secondary to hypoadrenocorticism. Cortisol was administered according to different protocols, which were chosen to provide extreme variations of the input signal. By this means, two phases of suppression of ACTH levels could be differentiated. A first decrease occurred without latency whenever, and as long as, plasma cortisol levels were rising. There was a linear regression between the logarithm of the increments in cortisol concentrations and the decrease in ACTH levels per minute (r = 0.951) (differential or rate-sensitive feedback mechanism). Neither the absolute doses of cortisol, nor plasma cortisol concentrations were closely correlated with the degree of suppression of ACTH by this rapid mechanism. A second decrease in ACTH levels began congruent with30 min after corticosteroid administration. In this case there was a significant linear regression between the degree of inhibition of ACTH levels and the cortisol doses (r = 0.997) (integral or dose-sensitive feedback mechanism). The dose-sensitive feedback effects of dexamethasone were less than might have been predicted from its relative anti-inflammatory potency. No rate-sensitive effects were seen with dexamethasone doses of 1.0 or 1.25 mg."}
{"id": "PMID:219035", "title": "Interactions between vitamin D deficiency and phosphorus depletion in the rat.", "content": "To evaluate the role of vitamin D in the physiologic response to phosphorus depletion (P depleton) and the response to vitamin D administration in P depletion, we studied vitamin D-deficient (-D) rats, fed either a normal or low phosphorus diet and then injected intraperitoneally on alternate days with replacement vitamin D(3), 1.25 mug qod (D(3)); 1.25-dihydroxy-vitamin D(3)[1,25(OH)(2)D(3)] in physiologic, 54 ng qod (LD), and pharmacologic doses, 400 ng qod (HD); or vehicle alone (-D). The following results were obtained: (a) With P depletion, urinary excretion of inorganic phosphorus (Pi) fell to almost undetectable levels in -D rats, and two physiologic features of P depletion a calcemic effect and hypercalciuria, ensued. (b) With administration of vitamin D(3) or 1,25(OH)(2)D(3) in either doses to P-depleted rats, the renal retention of Pi was unaltered despite a significant elevation of serum Pi. (c) The calcemic response to P depletion was accentuated by vitamin D sterols, and the hypercalciuria of P depletion was reduced by 1,25(OH)(2)D(3), HD > LD > D(3). (d) In -D animals receiving normal Pi (+P), D(3), and 1,25(OH)(2)D(3), both LD and HD produced a significant calcemic and phosphatemic effect. (e) Urinary Pi excretion in +P animals was reduced slightly by vitamin D(3) whereas 1,25(OH)(2)D(3), both LD and HD, lowered urinary Pi markedly despite an increased serum Pi. (f) The serial values of serum Ca and Pi and urinary Ca in PD rats and the sequential values for urinary and serum Pi in +P rats indicated more rapid effects of 1,25(OH)(2)D(3), both HD and LD, compared with D(3). We conclude that: (a) The renal adaptation and physiologic response to PD does not require the presence of vitamin D. (b) 1,25(OH)(2)D(3) may directly enhance the renal tubular reabsorption of Pi even as serum Pi rises. (c) A hypocalciuric action of 1,25(OH)(2)D(3) in rats on low phosphorus diet could be direct or occur as a consequence of an increase in serum Pi produced by 1,25(OH)(2)D(3). The different sequential renal response to D(3) compared with 1,25-(OH)(2)D(3) raises the possibility that other natural forms of vitamin D(3) [i.e., 25(OH)D(3), 24,25(OH)(2)D(3), etc.] which may be present in vitamin D-fed rats but not those given only 1,25(OH)(2)D(3), could modify the actions of 1,25(OH)(2)D(3).", "contents": "Interactions between vitamin D deficiency and phosphorus depletion in the rat. To evaluate the role of vitamin D in the physiologic response to phosphorus depletion (P depleton) and the response to vitamin D administration in P depletion, we studied vitamin D-deficient (-D) rats, fed either a normal or low phosphorus diet and then injected intraperitoneally on alternate days with replacement vitamin D(3), 1.25 mug qod (D(3)); 1.25-dihydroxy-vitamin D(3)[1,25(OH)(2)D(3)] in physiologic, 54 ng qod (LD), and pharmacologic doses, 400 ng qod (HD); or vehicle alone (-D). The following results were obtained: (a) With P depletion, urinary excretion of inorganic phosphorus (Pi) fell to almost undetectable levels in -D rats, and two physiologic features of P depletion a calcemic effect and hypercalciuria, ensued. (b) With administration of vitamin D(3) or 1,25(OH)(2)D(3) in either doses to P-depleted rats, the renal retention of Pi was unaltered despite a significant elevation of serum Pi. (c) The calcemic response to P depletion was accentuated by vitamin D sterols, and the hypercalciuria of P depletion was reduced by 1,25(OH)(2)D(3), HD > LD > D(3). (d) In -D animals receiving normal Pi (+P), D(3), and 1,25(OH)(2)D(3), both LD and HD produced a significant calcemic and phosphatemic effect. (e) Urinary Pi excretion in +P animals was reduced slightly by vitamin D(3) whereas 1,25(OH)(2)D(3), both LD and HD, lowered urinary Pi markedly despite an increased serum Pi. (f) The serial values of serum Ca and Pi and urinary Ca in PD rats and the sequential values for urinary and serum Pi in +P rats indicated more rapid effects of 1,25(OH)(2)D(3), both HD and LD, compared with D(3). We conclude that: (a) The renal adaptation and physiologic response to PD does not require the presence of vitamin D. (b) 1,25(OH)(2)D(3) may directly enhance the renal tubular reabsorption of Pi even as serum Pi rises. (c) A hypocalciuric action of 1,25(OH)(2)D(3) in rats on low phosphorus diet could be direct or occur as a consequence of an increase in serum Pi produced by 1,25(OH)(2)D(3). The different sequential renal response to D(3) compared with 1,25-(OH)(2)D(3) raises the possibility that other natural forms of vitamin D(3) [i.e., 25(OH)D(3), 24,25(OH)(2)D(3), etc.] which may be present in vitamin D-fed rats but not those given only 1,25(OH)(2)D(3), could modify the actions of 1,25(OH)(2)D(3)."}
{"id": "PMID:219036", "title": "Regulation of cytoplasmic dihydrotestosterone binding in dog prostate by 17 beta-estradiol.", "content": "17 beta-estradiol enchances androgen-induced prostate growth in the castrate dog to a degree comparable to that seen in spontaneous prostatic hypertrophy. To investigate the mechanism of this synergism, cytosol androgen binding was measured by a density gradient technique in prostates of control and 17 beta-estradiol-treated castrate dogs. [3H]Dihydrotestosterone was bound principally to a moiety that averaged 8.6S in size. Approximately twofold enhancement of this binding by 17 beta-estradiol was demonstrable after 1 wk of treatment with 750 microgram/wk and after 3 wk with 75 microgram/wk. Under conditions in which binding in the 8S region was demonstrable with dihydrotestosterone and testosterone no binding of 3 alpha-androstanediol or progesterone was detectable. Thus, enhancement by 17 beta-estradiol of a prostate cytosol androgen-binding protein occurs under circumstances in which 17 beta-estradiol enhances androgen-mediated prostatic growth.", "contents": "Regulation of cytoplasmic dihydrotestosterone binding in dog prostate by 17 beta-estradiol. 17 beta-estradiol enchances androgen-induced prostate growth in the castrate dog to a degree comparable to that seen in spontaneous prostatic hypertrophy. To investigate the mechanism of this synergism, cytosol androgen binding was measured by a density gradient technique in prostates of control and 17 beta-estradiol-treated castrate dogs. [3H]Dihydrotestosterone was bound principally to a moiety that averaged 8.6S in size. Approximately twofold enhancement of this binding by 17 beta-estradiol was demonstrable after 1 wk of treatment with 750 microgram/wk and after 3 wk with 75 microgram/wk. Under conditions in which binding in the 8S region was demonstrable with dihydrotestosterone and testosterone no binding of 3 alpha-androstanediol or progesterone was detectable. Thus, enhancement by 17 beta-estradiol of a prostate cytosol androgen-binding protein occurs under circumstances in which 17 beta-estradiol enhances androgen-mediated prostatic growth."}
{"id": "PMID:219037", "title": "The adrenal receptor for angiotensin II is altered in essential hypertension.", "content": "To determine the mechanism underlying altered adrenal responsiveness in patients with essential hypertension, the renin-angiotensin-aldosterone axis was assessed in normotensive and hypertensive subjects using three pharmacological probes: SQ 20881, a converting enzyme inhibitor; saralasin, a competitive angiotensin antagonist with prominent agonist properties; and angiotensin itself. All subjects were studied while supine and in balance on a 10 meq Na/100 meq K intake. The decrement in plasma aldosterone with SQ 20881 in 26 hypertensive subjects (15+/-3 ng/dl) was normal (13+/-4 ng/dl), suggesting that the altered adrenal responsiveness in hypertensives is not because of a change in a postreceptor event or in the relative contribution of angiotensin to the control of aldosterone secretion. Saralasin at a dose (0.1 mug/kg per min) that reduced aldosterone levels in all normals produced a normal aldosterone decrement (14+/-3 ng/dl) in 19 patients with renovascular hypertension (12+/-4 ng/dl). The same dose, however, had no net effect on plasma aldosterone levels in 70 patients with normal or high renin essential hypertension (-1+/-1 ng/dl) despite identical metabolic balance and control renin and angiotensin levels. The altered response could be explained by an agonist effect, aldosterone rising in 45 of the essential hypertensives. There were no significant differences between normal and abnormal responders in pre- and postcortisol, -potassium, -renin and -angiotensin concentrations. Angiotensin was infused (0.1-3 ng/kg per min) in 15 patients with normal renin essential hypertension, previously studied with saralasin. A probit transformation defined the dose required to induce a 50% increase in aldosterone (ED50). In the patients in whom aldosterone rose with saralasin, the dose required to induce a 50% increase was significantly greater (P < 0.001) than in those in whom aldosterone fell normally (1.02+/-0.06 [SD] vs. 0.38+/-0.07 ng/kg per min). Vascular responses were similar in the various groups. We conclude that altered adrenal responsiveness to angiotensin in some essential hypertensive patients is secondary to a change in the interaction of angiotensin with its adrenal receptor.", "contents": "The adrenal receptor for angiotensin II is altered in essential hypertension. To determine the mechanism underlying altered adrenal responsiveness in patients with essential hypertension, the renin-angiotensin-aldosterone axis was assessed in normotensive and hypertensive subjects using three pharmacological probes: SQ 20881, a converting enzyme inhibitor; saralasin, a competitive angiotensin antagonist with prominent agonist properties; and angiotensin itself. All subjects were studied while supine and in balance on a 10 meq Na/100 meq K intake. The decrement in plasma aldosterone with SQ 20881 in 26 hypertensive subjects (15+/-3 ng/dl) was normal (13+/-4 ng/dl), suggesting that the altered adrenal responsiveness in hypertensives is not because of a change in a postreceptor event or in the relative contribution of angiotensin to the control of aldosterone secretion. Saralasin at a dose (0.1 mug/kg per min) that reduced aldosterone levels in all normals produced a normal aldosterone decrement (14+/-3 ng/dl) in 19 patients with renovascular hypertension (12+/-4 ng/dl). The same dose, however, had no net effect on plasma aldosterone levels in 70 patients with normal or high renin essential hypertension (-1+/-1 ng/dl) despite identical metabolic balance and control renin and angiotensin levels. The altered response could be explained by an agonist effect, aldosterone rising in 45 of the essential hypertensives. There were no significant differences between normal and abnormal responders in pre- and postcortisol, -potassium, -renin and -angiotensin concentrations. Angiotensin was infused (0.1-3 ng/kg per min) in 15 patients with normal renin essential hypertension, previously studied with saralasin. A probit transformation defined the dose required to induce a 50% increase in aldosterone (ED50). In the patients in whom aldosterone rose with saralasin, the dose required to induce a 50% increase was significantly greater (P < 0.001) than in those in whom aldosterone fell normally (1.02+/-0.06 [SD] vs. 0.38+/-0.07 ng/kg per min). Vascular responses were similar in the various groups. We conclude that altered adrenal responsiveness to angiotensin in some essential hypertensive patients is secondary to a change in the interaction of angiotensin with its adrenal receptor."}
{"id": "PMID:219038", "title": "Hepatitis B virus antigens in primary hepatic carcinoma: immunofluorescent techniques on fixed liver tissue.", "content": "The presence of hepatitis B surface (HBsAg) and core (HBcAg) antigens was investigated by immunofluorescence in specimens of liver tissue obtained at necrospy in 107 patients with primary hepatic carcinoma. HBsAg was detected in the cytoplasm of liver cells in 16 cases, and in eight of them the antigen was also found in malignant cells. HBcAg, which was present in the nuclei of liver cells in eight cases, was detected in the nuclei of tumour cells in six of these and also in two other cases showing HBsAg, but not HBcAg, in the nonneoplastic tissue. Although most of the primary hepatic carcinomas studied were associated with cirrhotic changes in the non-neoplastic tissue, HBsAg and HBcAg were also detected in the absence of underlying cirrhosis. Hepatitis B virus markers were demonstrated in non-neoplastic tissue, mainly in patients with a well-differentiated carcinoma, and only in these cases were they found also in the neoplastic tissue. These results show that hepatitis B virus antigens, including HBcAg, can be detected in the neoplastic cells of well-differentiated carcinoma of the liver. Although these cells could have been infected after the malignant transformation, a direct oncogenic role of the virus cannot be excluded.", "contents": "Hepatitis B virus antigens in primary hepatic carcinoma: immunofluorescent techniques on fixed liver tissue. The presence of hepatitis B surface (HBsAg) and core (HBcAg) antigens was investigated by immunofluorescence in specimens of liver tissue obtained at necrospy in 107 patients with primary hepatic carcinoma. HBsAg was detected in the cytoplasm of liver cells in 16 cases, and in eight of them the antigen was also found in malignant cells. HBcAg, which was present in the nuclei of liver cells in eight cases, was detected in the nuclei of tumour cells in six of these and also in two other cases showing HBsAg, but not HBcAg, in the nonneoplastic tissue. Although most of the primary hepatic carcinomas studied were associated with cirrhotic changes in the non-neoplastic tissue, HBsAg and HBcAg were also detected in the absence of underlying cirrhosis. Hepatitis B virus markers were demonstrated in non-neoplastic tissue, mainly in patients with a well-differentiated carcinoma, and only in these cases were they found also in the neoplastic tissue. These results show that hepatitis B virus antigens, including HBcAg, can be detected in the neoplastic cells of well-differentiated carcinoma of the liver. Although these cells could have been infected after the malignant transformation, a direct oncogenic role of the virus cannot be excluded."}
{"id": "PMID:219039", "title": "Continuous-flow analysis of ammonia in perchloric acid supernate of blood or plasma using an ammonia-selective electrode.", "content": "A simple automated method for the estimation of ammonia in perchloric acid supernate of blood or plasma using an ion-selective electrode (Orion Ammonia-selective electrode, Model 95-10) is described. The reliability of the proposed method has been checked against an ion-exchange resin procedure, which has been chosen as a standard procedure. Regression equation and correlation coefficient for the proposed method are y = 0.7 X + 10 and 0.945, respectively, as compared with the chosen standard method. Within-run and between-run precision are 2.1% and 3.5% respectively. The average percent recovery is 97.5% and a tentative range is 13-73 microgram/dl (9-52 micronmol/l) ammonia nitrogen.", "contents": "Continuous-flow analysis of ammonia in perchloric acid supernate of blood or plasma using an ammonia-selective electrode. A simple automated method for the estimation of ammonia in perchloric acid supernate of blood or plasma using an ion-selective electrode (Orion Ammonia-selective electrode, Model 95-10) is described. The reliability of the proposed method has been checked against an ion-exchange resin procedure, which has been chosen as a standard procedure. Regression equation and correlation coefficient for the proposed method are y = 0.7 X + 10 and 0.945, respectively, as compared with the chosen standard method. Within-run and between-run precision are 2.1% and 3.5% respectively. The average percent recovery is 97.5% and a tentative range is 13-73 microgram/dl (9-52 micronmol/l) ammonia nitrogen."}
{"id": "PMID:219040", "title": "Mucin-producing atypical bronchial carcinoid.", "content": "In a case of atypical mucin-producing bronchial carcinoid in a 40-year-old man covert metastases were present at the time of lobectomy and were revealed at necropsy--a feature highlighting the malignant potential of the atypical carcinoid.", "contents": "Mucin-producing atypical bronchial carcinoid. In a case of atypical mucin-producing bronchial carcinoid in a 40-year-old man covert metastases were present at the time of lobectomy and were revealed at necropsy--a feature highlighting the malignant potential of the atypical carcinoid."}
{"id": "PMID:219041", "title": "Viruses in the stools.", "content": "It has long been possible to isolate viruses from the stools by culture, though the viruses found are rarely implicated in disease of the gut. In contrast, only recently has it been possible to identify viruses in the stools of patients with diarrhoea. Initially, such identifications were made by electron microscopy but the unsuitability of the microscope for large-scale screening has led to the development of other methods. The new methods have concentrated on rotaviruses but other viruses are also implicated and an overall view of the significance of finding a virus in any stool specimen has to take into account the evidence about all viruses, old and new.", "contents": "Viruses in the stools. It has long been possible to isolate viruses from the stools by culture, though the viruses found are rarely implicated in disease of the gut. In contrast, only recently has it been possible to identify viruses in the stools of patients with diarrhoea. Initially, such identifications were made by electron microscopy but the unsuitability of the microscope for large-scale screening has led to the development of other methods. The new methods have concentrated on rotaviruses but other viruses are also implicated and an overall view of the significance of finding a virus in any stool specimen has to take into account the evidence about all viruses, old and new."}
{"id": "PMID:219042", "title": "Granular cell myoblastoma: positive staining for carcinoembryonic antigen.", "content": "An immunoperoxidase technique for the detection of carcinoembryonic antigen was applied to 10 cases of granular cell myoblastoma. Consistent, strong, intracytoplasmic granular staining, which can be easily interpreted, was obtained in all cases. Schwannomas, neurofibromas, dermatofibromas, and leiomyomas were negative. The test is helpful in confirming doubtful cases. The results tend to support the suggestion that granular cell myoblastoma is derived from perineural rather than endoneural cells.", "contents": "Granular cell myoblastoma: positive staining for carcinoembryonic antigen. An immunoperoxidase technique for the detection of carcinoembryonic antigen was applied to 10 cases of granular cell myoblastoma. Consistent, strong, intracytoplasmic granular staining, which can be easily interpreted, was obtained in all cases. Schwannomas, neurofibromas, dermatofibromas, and leiomyomas were negative. The test is helpful in confirming doubtful cases. The results tend to support the suggestion that granular cell myoblastoma is derived from perineural rather than endoneural cells."}
{"id": "PMID:219043", "title": "Detection of inferior vena cava abnormalities by computed tomography.", "content": "The diagnostically useful computed tomography (CT) findings in five new cases of inferior vena cava thrombosis are reported. These findings include: (a) inhomogeneous density of the inferior vena cava, usually best demonstrated after contrast medium injection; (b) caval density less than aortic density; (c) rim enhancement which may be seen with both caval thrombosis and tumor invasion; and (d) enlargement of the vena cava if accompanied by at least one or more of the above findings. A bolus injection of contrast medium followed immediately by CT helps to make some of the above described findings more prominent. In selected patients, this injection should be made into the femoral vein.", "contents": "Detection of inferior vena cava abnormalities by computed tomography. The diagnostically useful computed tomography (CT) findings in five new cases of inferior vena cava thrombosis are reported. These findings include: (a) inhomogeneous density of the inferior vena cava, usually best demonstrated after contrast medium injection; (b) caval density less than aortic density; (c) rim enhancement which may be seen with both caval thrombosis and tumor invasion; and (d) enlargement of the vena cava if accompanied by at least one or more of the above findings. A bolus injection of contrast medium followed immediately by CT helps to make some of the above described findings more prominent. In selected patients, this injection should be made into the femoral vein."}
{"id": "PMID:219044", "title": "Decreased cAMP levels in human diploid cells exposed to cholinergic stimuli.", "content": "Carbachol at a concentration of 1 micron caused very significant decreases in PGE1 stimulated cAMP levels in three human diploid lung fibroblasts, WI-38, MRC-5, and IMR-90. Detailed studies with WI-38 cells showed that carbachol acted at low concentrations and very rapidly, cAMP levels being reduced by 50% in about 1 minute. The effect was moderately reduced but still very significant in Ca++ free medium containing 10(-5)M EGTA. Acetylcholine (in the presence of physostigmine), pilocarpine, and muscarine lowered cAMP levels at concentrations of 1 or 10 micron. The effects of carbachol were exquisitely sensitive to atropine but were unaffected by hexomethonium or d-tubocurarine. These data suggested that the cholinergic response of WI-38 cells was of the muscarinic type.", "contents": "Decreased cAMP levels in human diploid cells exposed to cholinergic stimuli. Carbachol at a concentration of 1 micron caused very significant decreases in PGE1 stimulated cAMP levels in three human diploid lung fibroblasts, WI-38, MRC-5, and IMR-90. Detailed studies with WI-38 cells showed that carbachol acted at low concentrations and very rapidly, cAMP levels being reduced by 50% in about 1 minute. The effect was moderately reduced but still very significant in Ca++ free medium containing 10(-5)M EGTA. Acetylcholine (in the presence of physostigmine), pilocarpine, and muscarine lowered cAMP levels at concentrations of 1 or 10 micron. The effects of carbachol were exquisitely sensitive to atropine but were unaffected by hexomethonium or d-tubocurarine. These data suggested that the cholinergic response of WI-38 cells was of the muscarinic type."}
{"id": "PMID:219045", "title": "Quantitative labeling of the regulatory subunit of type II cAMP-dependent protein kinase from bovine heart by a photoaffinity analog.", "content": "Several methods were compared for estimating the amount of regulatory subunit of an 800-fold purified Type II cAMP-dependent protein kinase from bovine heart. These methods included a reversable binding assay using either cAMP, or 8-N3-[32P]cAMP, photoaffinity labeling with 8-N3-[32P]cAMP, and autophosphorylation of the regulatory subunit of the enzyme. Although the regulatory subunit had a slightly lower affinity for 8-N3-cAMP than for cAMP, the total amount of regulatory subunit could be determined by each of the procedures examined. The results indicate that the photoaffinity analog 8-N3-[32P]cAMP is able to label quantitatively all cAMP-binding sites of the regulatory subunit of this cAMP-dependent protein kinase.", "contents": "Quantitative labeling of the regulatory subunit of type II cAMP-dependent protein kinase from bovine heart by a photoaffinity analog. Several methods were compared for estimating the amount of regulatory subunit of an 800-fold purified Type II cAMP-dependent protein kinase from bovine heart. These methods included a reversable binding assay using either cAMP, or 8-N3-[32P]cAMP, photoaffinity labeling with 8-N3-[32P]cAMP, and autophosphorylation of the regulatory subunit of the enzyme. Although the regulatory subunit had a slightly lower affinity for 8-N3-cAMP than for cAMP, the total amount of regulatory subunit could be determined by each of the procedures examined. The results indicate that the photoaffinity analog 8-N3-[32P]cAMP is able to label quantitatively all cAMP-binding sites of the regulatory subunit of this cAMP-dependent protein kinase."}
{"id": "PMID:219046", "title": "Protein kinases in developing rat brain.", "content": "The levels of cAMP-dependent protein kinases were measured in developing rat brain by a variety of methods. The regulatory subunit (R) was measured both by [3H]cAMP binding and by 8-N3-[32P]cAMP incorporation. The catalytic subunit (C) was measured by an assay of histone kinase activity. Data were calculated per mg protein. Neither R nor C levels changed significantly in either membranes or cytosol during development. The ratio of R to C was essentially unity in the cerebra of both newborn (2-day-old) and adult (40-day-old) rats. Polyacrylamide-gel electrophoresis resolved two regulatory subunits (R-I) and (R-II) which were derived from the Type I and Type II cAMP-dependent protein kinases, respectively. 8-N3-[32P]cAMP incorporation into Proteins R-I and R-II indicated that the amounts of Proteins R-I and R-II did not change significantly in either membranes or cytosol during development.", "contents": "Protein kinases in developing rat brain. The levels of cAMP-dependent protein kinases were measured in developing rat brain by a variety of methods. The regulatory subunit (R) was measured both by [3H]cAMP binding and by 8-N3-[32P]cAMP incorporation. The catalytic subunit (C) was measured by an assay of histone kinase activity. Data were calculated per mg protein. Neither R nor C levels changed significantly in either membranes or cytosol during development. The ratio of R to C was essentially unity in the cerebra of both newborn (2-day-old) and adult (40-day-old) rats. Polyacrylamide-gel electrophoresis resolved two regulatory subunits (R-I) and (R-II) which were derived from the Type I and Type II cAMP-dependent protein kinases, respectively. 8-N3-[32P]cAMP incorporation into Proteins R-I and R-II indicated that the amounts of Proteins R-I and R-II did not change significantly in either membranes or cytosol during development."}
{"id": "PMID:219047", "title": "Actomyosin from mammary myoepithelial cells and phosphorylation by myosin light chain kinase.", "content": "The oxytocin-sensitive myoepithelial cells of the mammary gland form a system with characteristics of a potentially useful model for studying the mechanism of action of oxytocin and coupling phenomena of excitation-contraction. Our objectives were to develop a method for isolating mammary actomyosin, to determine the amount of actomyosin in the glands of lactating and nonlactating animals, and to investigate control of contractile protein interaction. Actomyosin in mammary glands represented a substantial portion of the soluble protein in the gland ranging from 9% of the total in lactating to 17% in weaned rats. The isolated actomyosin had a molecular composition like that of actomyosin of smooth muscle and the isolated actomyosin contained a light chain kinase that phosphorylated the 20,000 dalton light chain of myosin (L20). The kinase isolated as a component of actomyosin preparations did not show calcium control, but it did when isolated from mammary cytosol. Strips of involuted mammary tissue from rats developed tension when oxytocin was added to the bathing medium; thus, the myoepithelial cells appeared to retain their sensitivity to oxytocin even in nonlactating animals and may be a useful model for studying the action of oxytocin. We suggest that one of the final steps in the milk-ejection reflex is phosphorylation of myosin causing a contraction of the myoepithelial cells of the mammary gland.", "contents": "Actomyosin from mammary myoepithelial cells and phosphorylation by myosin light chain kinase. The oxytocin-sensitive myoepithelial cells of the mammary gland form a system with characteristics of a potentially useful model for studying the mechanism of action of oxytocin and coupling phenomena of excitation-contraction. Our objectives were to develop a method for isolating mammary actomyosin, to determine the amount of actomyosin in the glands of lactating and nonlactating animals, and to investigate control of contractile protein interaction. Actomyosin in mammary glands represented a substantial portion of the soluble protein in the gland ranging from 9% of the total in lactating to 17% in weaned rats. The isolated actomyosin had a molecular composition like that of actomyosin of smooth muscle and the isolated actomyosin contained a light chain kinase that phosphorylated the 20,000 dalton light chain of myosin (L20). The kinase isolated as a component of actomyosin preparations did not show calcium control, but it did when isolated from mammary cytosol. Strips of involuted mammary tissue from rats developed tension when oxytocin was added to the bathing medium; thus, the myoepithelial cells appeared to retain their sensitivity to oxytocin even in nonlactating animals and may be a useful model for studying the action of oxytocin. We suggest that one of the final steps in the milk-ejection reflex is phosphorylation of myosin causing a contraction of the myoepithelial cells of the mammary gland."}
{"id": "PMID:219050", "title": "Mobilizing nursing skills.", "content": "The author argues that the practice of nursing should be based on the \"nursing model\" related to care not the \"medical model\" related to cure. Using the nursing model entails making an assessment of the patient's needs and an individualized nursing care plan to meet them. It is conceded that the historical development of nursing practice as a series of stereotyped, ritualized activities within a hierarchical profession militates against implementing the nursing model; but the author illustrates how to Royal Marsden Hospital, a specialist hospital for the treatment of cancer patients, has innovated and developed the concept, as well as creating specialist roles for nurses who maintain continuity of patient care from the first appointment in the hospital's outpatients' clinic through to this after-care following his discharge home.", "contents": "Mobilizing nursing skills. The author argues that the practice of nursing should be based on the \"nursing model\" related to care not the \"medical model\" related to cure. Using the nursing model entails making an assessment of the patient's needs and an individualized nursing care plan to meet them. It is conceded that the historical development of nursing practice as a series of stereotyped, ritualized activities within a hierarchical profession militates against implementing the nursing model; but the author illustrates how to Royal Marsden Hospital, a specialist hospital for the treatment of cancer patients, has innovated and developed the concept, as well as creating specialist roles for nurses who maintain continuity of patient care from the first appointment in the hospital's outpatients' clinic through to this after-care following his discharge home."}
{"id": "PMID:219051", "title": "Changes in hormonal activities relative to the severity of essential hypertension.", "content": "Endocrine activity in patients with essential hypertension was studied by measuring the urinary excretion of catecholamines, prostaglandin E (PGE) and cyclic adenosine monophosphate (cAMP). Simultaneously, plasma renin activity, concentrations of serum sodium, potassium, blood urea nitrogen (BUN) and creatinine were determined. Systolic blood pressure and BUN increased progressively with age until the sixth decade. Urinary excretion of norepinephrine was correlated with the systolic blood pressure. In contrast, plasma renin activity and urinary excretion of PGE decreased progressively with the increase in systolic blood pressure. Although the cause of essential hypertension is not known, it is suggested that hypertension accelerates the aging process in the kidney and thus decreases renal PGE synthesis. This decrease of PGE in turn causes a reduction of plasma renin activity, possibly either by accelerating the retention of sodium and water or by failing to stimulate renin synthesis. A decrease of PGE may also potentiate the vasopressor action of norepinephrine.", "contents": "Changes in hormonal activities relative to the severity of essential hypertension. Endocrine activity in patients with essential hypertension was studied by measuring the urinary excretion of catecholamines, prostaglandin E (PGE) and cyclic adenosine monophosphate (cAMP). Simultaneously, plasma renin activity, concentrations of serum sodium, potassium, blood urea nitrogen (BUN) and creatinine were determined. Systolic blood pressure and BUN increased progressively with age until the sixth decade. Urinary excretion of norepinephrine was correlated with the systolic blood pressure. In contrast, plasma renin activity and urinary excretion of PGE decreased progressively with the increase in systolic blood pressure. Although the cause of essential hypertension is not known, it is suggested that hypertension accelerates the aging process in the kidney and thus decreases renal PGE synthesis. This decrease of PGE in turn causes a reduction of plasma renin activity, possibly either by accelerating the retention of sodium and water or by failing to stimulate renin synthesis. A decrease of PGE may also potentiate the vasopressor action of norepinephrine."}
{"id": "PMID:219053", "title": "[Ocular herpes : clinical variations and virus antigenic type (author's transl)].", "content": "Fifty-seven herpes simplex virus strains, isolated from ocular herpes, were screened by complement fixation, seroneutralization and thermosensitivity tests. They were distributed as follows : 44 type 1, 3 type 2, 7 intermediate type ; 3 had a type 2 thermosensitivity and a type 1 neutralization. Discrepancies in these results, with the three tests, show that there is, in each typed group, strains of virus which react differently, and this could indicate a continuity from one type to another. As the strain progressively reacts more like the type 2, clinical symptoms become more severe. In a certain number of cases where several simultaneous or successive samples were performed, there was a hypothetic possibility of change in the behaviour of herpes simplex virus strains in the eye.", "contents": "[Ocular herpes : clinical variations and virus antigenic type (author's transl)]. Fifty-seven herpes simplex virus strains, isolated from ocular herpes, were screened by complement fixation, seroneutralization and thermosensitivity tests. They were distributed as follows : 44 type 1, 3 type 2, 7 intermediate type ; 3 had a type 2 thermosensitivity and a type 1 neutralization. Discrepancies in these results, with the three tests, show that there is, in each typed group, strains of virus which react differently, and this could indicate a continuity from one type to another. As the strain progressively reacts more like the type 2, clinical symptoms become more severe. In a certain number of cases where several simultaneous or successive samples were performed, there was a hypothetic possibility of change in the behaviour of herpes simplex virus strains in the eye."}
{"id": "PMID:219054", "title": "Effect of age and sex on triglyceride metabolism in the rat.", "content": "The effect of age and sex on triglyceride metabolism were investigated in 3-mo- and 1-year-old rats. Although 3-mo-old female rats produce as much triglyceride as comparably aged male rats, their plasma triglyceride levels are lower. This suggests that 3-mo-old female rats remove triglycerides from plasma more efficiently than do similar aged male rats, and this is supported by the observation that the t1/2 of very low density lipoprotein triglyceride removal is somewhat faster in female rats of this age (p less than 0.1 greater than 0.5). As rats grow to 1 year of age, the ability of both sexes to remove triglycerides from plasma deteriorates, resulting in a rise in plasma triglyceride levels. The decrease in efficiency of triglyceride removal from plasma in female rats is coupled with an increase in triglyceride production rate, leading to an even greater increase in triglyceride levels. These results indicate that both age and sex modify triglyceride metabolism in the rat.", "contents": "Effect of age and sex on triglyceride metabolism in the rat. The effect of age and sex on triglyceride metabolism were investigated in 3-mo- and 1-year-old rats. Although 3-mo-old female rats produce as much triglyceride as comparably aged male rats, their plasma triglyceride levels are lower. This suggests that 3-mo-old female rats remove triglycerides from plasma more efficiently than do similar aged male rats, and this is supported by the observation that the t1/2 of very low density lipoprotein triglyceride removal is somewhat faster in female rats of this age (p less than 0.1 greater than 0.5). As rats grow to 1 year of age, the ability of both sexes to remove triglycerides from plasma deteriorates, resulting in a rise in plasma triglyceride levels. The decrease in efficiency of triglyceride removal from plasma in female rats is coupled with an increase in triglyceride production rate, leading to an even greater increase in triglyceride levels. These results indicate that both age and sex modify triglyceride metabolism in the rat."}
{"id": "PMID:219055", "title": "Some age-related changes in pituitary-adrenal function in the male laboratory rat.", "content": "Changes in the pituitary-adrenal axis have been investigated as a function of age (2 1/2 to 26 mo) in the male laboratory rat (CFY-Sprague Dawley). Ether stress was used to challenge the pituitary-adrenal axis and blood samples (peripheral and adrenal venous effluent) taken for measurement of corticosterone using the competitive protein-binding assay and ACTH by the increase in corticosteroidogenesis in isolated rat adrenal cells. The results show that there was an increase of basal ACTH levels with increase in age which might be correlated with the degenerative changes in the adrenal cortex at old age. No age difference was observed in the 2 1/2-min stress levels. However, 15-min stress resulted in a further increment of ACTH levels, which was not found in old animals. No age-related differences in the basal and stress levels of corticosterone was observed, and, hence, adrenocortical function would seem not to be impaired in old age.", "contents": "Some age-related changes in pituitary-adrenal function in the male laboratory rat. Changes in the pituitary-adrenal axis have been investigated as a function of age (2 1/2 to 26 mo) in the male laboratory rat (CFY-Sprague Dawley). Ether stress was used to challenge the pituitary-adrenal axis and blood samples (peripheral and adrenal venous effluent) taken for measurement of corticosterone using the competitive protein-binding assay and ACTH by the increase in corticosteroidogenesis in isolated rat adrenal cells. The results show that there was an increase of basal ACTH levels with increase in age which might be correlated with the degenerative changes in the adrenal cortex at old age. No age difference was observed in the 2 1/2-min stress levels. However, 15-min stress resulted in a further increment of ACTH levels, which was not found in old animals. No age-related differences in the basal and stress levels of corticosterone was observed, and, hence, adrenocortical function would seem not to be impaired in old age."}
{"id": "PMID:219108", "title": "The effect of relative humidity on swine vesicular disease virus in dried films before and during formaldehyde fumigation.", "content": "Swine Vesicular Disease virus (SVDV) did not survive drying at high relative humidities (r.h.) but there was little virus loss at low r.h. Purified virus dried in films was inactivated by formaldehyde fumigation only at high r.h. Inactivation was also influenced by the suspending medium from which the virus was dried. Purified virus resuspended in distilled water and then dried, was rapidly killed, but that in tissue culture fluid survived.", "contents": "The effect of relative humidity on swine vesicular disease virus in dried films before and during formaldehyde fumigation. Swine Vesicular Disease virus (SVDV) did not survive drying at high relative humidities (r.h.) but there was little virus loss at low r.h. Purified virus dried in films was inactivated by formaldehyde fumigation only at high r.h. Inactivation was also influenced by the suspending medium from which the virus was dried. Purified virus resuspended in distilled water and then dried, was rapidly killed, but that in tissue culture fluid survived."}
{"id": "PMID:219109", "title": "The inactivation of viruses in cattle and pig slurry by aeration or treatment with calcium hydroxide.", "content": "Porcine enterovirus type 2 or porcine adenovirus type 3 were seeded into samples of pig slurry, and a bovine enterovirus was seeded into cattle slurry, and samples of the slurry were aerated in the laboratory for 21 days. The viruses were inactivated more rapidly in the aerated slurry than in control slurry which was not aerated. The difference in inactivation rate was greatest for the porcine adenovirus and least for the bovine enterovirus. Inactivation of the porcine enterovirus in aerated distilled water and in aerated, autoclaved pig slurry proceeded at a similar rate as in the same materials which were not aerated. Ten samples of aerated slurry were collected from an aeration tank which received weekly additions of raw pig slurry which was sampled at the same times. Each sample yielded a porcine enterovirus after concentration with the polyelectrolyte PE-60, but in three comparative titrations the viral infectivity titre in concentrates of the raw slurry was at least 1000 times greater than in the aerated slurry. Porcine enterovirus type 2 and porcine adenovirus type 3, which were seeded into pig slurry, and a bovine enterovirus seeded into cattle slurry, were inactivated by treatment of the slurry with calcium hydroxide at pH 11.5. The inactivation rate was highest for the bovine enterovirus and lowest for the porcine adenovirus.", "contents": "The inactivation of viruses in cattle and pig slurry by aeration or treatment with calcium hydroxide. Porcine enterovirus type 2 or porcine adenovirus type 3 were seeded into samples of pig slurry, and a bovine enterovirus was seeded into cattle slurry, and samples of the slurry were aerated in the laboratory for 21 days. The viruses were inactivated more rapidly in the aerated slurry than in control slurry which was not aerated. The difference in inactivation rate was greatest for the porcine adenovirus and least for the bovine enterovirus. Inactivation of the porcine enterovirus in aerated distilled water and in aerated, autoclaved pig slurry proceeded at a similar rate as in the same materials which were not aerated. Ten samples of aerated slurry were collected from an aeration tank which received weekly additions of raw pig slurry which was sampled at the same times. Each sample yielded a porcine enterovirus after concentration with the polyelectrolyte PE-60, but in three comparative titrations the viral infectivity titre in concentrates of the raw slurry was at least 1000 times greater than in the aerated slurry. Porcine enterovirus type 2 and porcine adenovirus type 3, which were seeded into pig slurry, and a bovine enterovirus seeded into cattle slurry, were inactivated by treatment of the slurry with calcium hydroxide at pH 11.5. The inactivation rate was highest for the bovine enterovirus and lowest for the porcine adenovirus."}
{"id": "PMID:219111", "title": "Improved performance of a double antibody radioimmunoassay for carcinoembryonic antigen.", "content": "A new double antibody solid-phase radioimmunoassay (RIA) for carcinoembryonic antigen (CEA) is critically analyzed. The aim of the study was 4-fold: (a) to define the level of sensitivity (a comparison of 3 different assay procedures revealed that our sequential assay was more sensitive than most previously reported RIAs, while competitive and non-equilibrium assay had wider measuring ranges); (b) to analyze recoveries of CEA in either serum, plasma or urine (the recovery, even in urine, was very close to expected values, indicating that no CEA is lost or degraded during brief storage or in the extraction procedure); (c) to evaluate inter- and intra-assay variations, since most clinical management is dependent on serial assays rather than single determinations. The coefficients of variation were low both within and between assays. A change of 3 ng CEA is required for significant change (greater than 2 S.D.) at the normal serum level which is 16 ng CEA/ml in our assay. At levels above normal, a change of 4 ng is required; (d) the assay was also developed for determination of CEA levels in a large series of perchlorid acid treated serum, plasma or urine samples. This forms the basis for an assay suitable for serial assays with high sensitivity and accuracy in various neoplastic diseases.", "contents": "Improved performance of a double antibody radioimmunoassay for carcinoembryonic antigen. A new double antibody solid-phase radioimmunoassay (RIA) for carcinoembryonic antigen (CEA) is critically analyzed. The aim of the study was 4-fold: (a) to define the level of sensitivity (a comparison of 3 different assay procedures revealed that our sequential assay was more sensitive than most previously reported RIAs, while competitive and non-equilibrium assay had wider measuring ranges); (b) to analyze recoveries of CEA in either serum, plasma or urine (the recovery, even in urine, was very close to expected values, indicating that no CEA is lost or degraded during brief storage or in the extraction procedure); (c) to evaluate inter- and intra-assay variations, since most clinical management is dependent on serial assays rather than single determinations. The coefficients of variation were low both within and between assays. A change of 3 ng CEA is required for significant change (greater than 2 S.D.) at the normal serum level which is 16 ng CEA/ml in our assay. At levels above normal, a change of 4 ng is required; (d) the assay was also developed for determination of CEA levels in a large series of perchlorid acid treated serum, plasma or urine samples. This forms the basis for an assay suitable for serial assays with high sensitivity and accuracy in various neoplastic diseases."}
{"id": "PMID:219110", "title": "Specific immunoglobulin responses after varicella and herpes zoster.", "content": "The indirect immunofluorescence technique has been used to titrate the specific immunoglobulins in 200 sera from 64 patients with varicella, and 195 sera from 67 patients with herpes zoster. IgG and IgM antibodies were detected in all patients with varicella, and IgA in 59 (92%). All three classes of antibody appeared 2--5 days after the onset of the rash, increased virtually simultaneously and reached maximum titres during the second and third weeks. IgG then declined slowly, but never became undetectable and was still present in five subjects who were retested after 2--4 years; it was present in 88 out of 100 healthy young adults and probably persists indefinitely after varicella. IgA and IgM antibodies declined more rapidly and were not detected in specimens taken more than a year after the illness. IgA, however, may possibly persist in some cases since low titres were found in 8 out of 88 young adults who possessed IgG antibody and had presumably had varicella in the past. IgA responses were significantly weaker in children under the age of 6 years than in older children and adults. Six out of 67 patients with zoster were tested at various times before the onset of the rash: IgG antibody was detected in all. IgG was present in all sera taken after the onset of the rash, increased rapidly after 2--5 days, reached maximum titres during the second and third weeks and then declined slowly. IgA antibody was detected in 66 patients (99%) and IgM in 52 (78%); both types of antibody followed transient courses, as in varicella. Maximum titres of IgG and complement-fixing antibodies were greater after zoster than after varicella, but the differences were not significant. IgA and IgM titres in young adults with zoster were significantly lower than in older patients, and also lower than in young adults with varicella. Increases in varicella-zoster antibody in patients with herpes simplex virus infections consisted mainly of IgG, sometimes IgA, but never IgM.", "contents": "Specific immunoglobulin responses after varicella and herpes zoster. The indirect immunofluorescence technique has been used to titrate the specific immunoglobulins in 200 sera from 64 patients with varicella, and 195 sera from 67 patients with herpes zoster. IgG and IgM antibodies were detected in all patients with varicella, and IgA in 59 (92%). All three classes of antibody appeared 2--5 days after the onset of the rash, increased virtually simultaneously and reached maximum titres during the second and third weeks. IgG then declined slowly, but never became undetectable and was still present in five subjects who were retested after 2--4 years; it was present in 88 out of 100 healthy young adults and probably persists indefinitely after varicella. IgA and IgM antibodies declined more rapidly and were not detected in specimens taken more than a year after the illness. IgA, however, may possibly persist in some cases since low titres were found in 8 out of 88 young adults who possessed IgG antibody and had presumably had varicella in the past. IgA responses were significantly weaker in children under the age of 6 years than in older children and adults. Six out of 67 patients with zoster were tested at various times before the onset of the rash: IgG antibody was detected in all. IgG was present in all sera taken after the onset of the rash, increased rapidly after 2--5 days, reached maximum titres during the second and third weeks and then declined slowly. IgA antibody was detected in 66 patients (99%) and IgM in 52 (78%); both types of antibody followed transient courses, as in varicella. Maximum titres of IgG and complement-fixing antibodies were greater after zoster than after varicella, but the differences were not significant. IgA and IgM titres in young adults with zoster were significantly lower than in older patients, and also lower than in young adults with varicella. Increases in varicella-zoster antibody in patients with herpes simplex virus infections consisted mainly of IgG, sometimes IgA, but never IgM."}
{"id": "PMID:219116", "title": "Neutrophil myeloperoxidase: a simple, reproducible technique to determine activity.", "content": "Neutrophil MPO deficiency has been rarely documented. This is because of the low incidence of infections in these individuals and the lack of use of various screening techniques which would detect them. Using the Hemalog D, we have identified one completely deficient and 18 partially deficient subjects. These subjects were studied by staining their peripheral blood smears for MPO and grading the intensity of the stain on 100 consecutive neutrophils (MPO score) as well as by chemically quantifying the MPO activity. There is an excellent correlation between MPO score and quantitated MPO activity. The MPO score is a simple semiquantitative method to estimate MPO activity.", "contents": "Neutrophil myeloperoxidase: a simple, reproducible technique to determine activity. Neutrophil MPO deficiency has been rarely documented. This is because of the low incidence of infections in these individuals and the lack of use of various screening techniques which would detect them. Using the Hemalog D, we have identified one completely deficient and 18 partially deficient subjects. These subjects were studied by staining their peripheral blood smears for MPO and grading the intensity of the stain on 100 consecutive neutrophils (MPO score) as well as by chemically quantifying the MPO activity. There is an excellent correlation between MPO score and quantitated MPO activity. The MPO score is a simple semiquantitative method to estimate MPO activity."}
{"id": "PMID:219117", "title": "Structure activity relationships between catecholamines and the alpha-adrenergic receptor responsible for the aggregation of human platelets by epinephrine.", "content": "PEA is a potent inhibitor (Ki approximately 13 microM) of human platelet aggregation induced by epinephrine. This led us to perform an SAR study of a congeneric series of compounds in an effort to identify the molecular components of epinephrine critical to its aggregating effect upon human platelets. Phenylethanolamine was similar to PEA in inhibitory potency. However, hydroxylation of the phenyl ring diminished the inhibitory effect (Ki tyramine approximately 87 microM; Ki octopamine approximately 88 microM). Dopamine, the weakest inhibitor (Ki approximately 150 microM), was a partial agonist capable of inducing platelet aggregation in some samples of PRP. The order of potency of catecholamines as aggregating agents was epinephrine greater than norepinephrine greater than Epinine greater than dopamine. Phenylephrine, the prototype alpha-agonist, did not induce aggregation but was a potent inhibitor (Ki approximately 12 microM) of the aggregation induced by epinephrine. Isoproterenol, the prototype beta-agonist, was neither an aggregant nor an inhibitor of epinephrine-induced platelet aggregation. These findings suggest that the binding of epinephrine to the alpha-adrenergic receptor responsible for platelet aggregation is accomplished by the N-methyl amino group whereas intrinsic aggregating activity is a function of the catechol moiety.", "contents": "Structure activity relationships between catecholamines and the alpha-adrenergic receptor responsible for the aggregation of human platelets by epinephrine. PEA is a potent inhibitor (Ki approximately 13 microM) of human platelet aggregation induced by epinephrine. This led us to perform an SAR study of a congeneric series of compounds in an effort to identify the molecular components of epinephrine critical to its aggregating effect upon human platelets. Phenylethanolamine was similar to PEA in inhibitory potency. However, hydroxylation of the phenyl ring diminished the inhibitory effect (Ki tyramine approximately 87 microM; Ki octopamine approximately 88 microM). Dopamine, the weakest inhibitor (Ki approximately 150 microM), was a partial agonist capable of inducing platelet aggregation in some samples of PRP. The order of potency of catecholamines as aggregating agents was epinephrine greater than norepinephrine greater than Epinine greater than dopamine. Phenylephrine, the prototype alpha-agonist, did not induce aggregation but was a potent inhibitor (Ki approximately 12 microM) of the aggregation induced by epinephrine. Isoproterenol, the prototype beta-agonist, was neither an aggregant nor an inhibitor of epinephrine-induced platelet aggregation. These findings suggest that the binding of epinephrine to the alpha-adrenergic receptor responsible for platelet aggregation is accomplished by the N-methyl amino group whereas intrinsic aggregating activity is a function of the catechol moiety."}
{"id": "PMID:219119", "title": "Effects of a chemotactic factor, N-formylmethionyl peptide, on adherence, superoxide anion generation, phagocytosis, and microtubule assembly of human polymorphonuclear leukocytes.", "content": "FMLP promoted microtubule assembly in PMNs at concentrations which were chemotactic for the cells. At higher concentrations than those required for chemotaxis, FMLP enhanced the adherence of PMNs to nylon glass fibers. With colchicine, PMN adherence was inhibited, but upon exposure to FMLP, PMN adherence could be restored. The effect of FMLP on PMN adherence was transitory and was no longer evident by 5 min. At concentrations similar to those employed in the adherence studies. FMLP induced the cells to briefly generate O-2, since ferricytochrome C reduction was no longer evident by 5 min. Pretreatment of the PMNs with cytochalasin B enhanced the release of O-2 by PMNs exposed to FMLP. On the other hand, there was no effect of FMLP on phagocytosis of C3-coated particles. These results suggest that FMLP induces responsive cells to develop a hyperadherent plasma membrane which is largely independent on microtubule control. Since oligopeptides similar of AMLP are formed in bacteria, it is likely that the action of N-formylated peptides is important in regulating the inflammatory response.", "contents": "Effects of a chemotactic factor, N-formylmethionyl peptide, on adherence, superoxide anion generation, phagocytosis, and microtubule assembly of human polymorphonuclear leukocytes. FMLP promoted microtubule assembly in PMNs at concentrations which were chemotactic for the cells. At higher concentrations than those required for chemotaxis, FMLP enhanced the adherence of PMNs to nylon glass fibers. With colchicine, PMN adherence was inhibited, but upon exposure to FMLP, PMN adherence could be restored. The effect of FMLP on PMN adherence was transitory and was no longer evident by 5 min. At concentrations similar to those employed in the adherence studies. FMLP induced the cells to briefly generate O-2, since ferricytochrome C reduction was no longer evident by 5 min. Pretreatment of the PMNs with cytochalasin B enhanced the release of O-2 by PMNs exposed to FMLP. On the other hand, there was no effect of FMLP on phagocytosis of C3-coated particles. These results suggest that FMLP induces responsive cells to develop a hyperadherent plasma membrane which is largely independent on microtubule control. Since oligopeptides similar of AMLP are formed in bacteria, it is likely that the action of N-formylated peptides is important in regulating the inflammatory response."}
{"id": "PMID:219121", "title": "The in vivo metabolism of esterified cholesterol in the plasma high-density lipoproteins of rabbits.", "content": "The in vivo metabolism of esterified cholesterol in plasma HDL has been studied in rabbits injected with preparations of HDL which had been labeled with 3H in the esterified and free cholesterol moieties. These labeled HDL preparations had been isolated either from the serum of donor rabbits which had been previously injected with 3H-mevalonic acid or from rabbit serum which had been incubated in vitro at 37 degrees with 3H-cholesterol. In terms of subsequent in vivo metabolism, there were no significant differences between the in vivo labeled and in vitro labeled HDL preparations. It was also found that the presence of free 3H-cholesterol in the injected HDL had very little effect on the recipient esterified 3H-cholesterol results. The removal of esterified 3H-cholesterol from the recipient HDL fraction was biphasic, with the initial phase largely reflecting a transfer into the plasma VLDL and LDL fractions rather than a removal from the plasma compartment. In fact, the initial rate of removal from HDL was very much influenced by the distribution of esterified cholesterol mass in the different lipoprotein fractions; the greater the proportion in VLDL and LDL, the more rapid was the initial rate of removal from HDL. A transfer of esterified cholesterol from HDL to VLDL and LDL was estimated to be of the order of 150 to 200 mumol/L of plasma per hour, a value much greater than the reported rate of production of esterified cholesterol in rabbit plasma. The implication that such transfers might therefore have been partially reversible was confirmed in in vitro incubations of labeled HDL and unlabeled rabbit serum.", "contents": "The in vivo metabolism of esterified cholesterol in the plasma high-density lipoproteins of rabbits. The in vivo metabolism of esterified cholesterol in plasma HDL has been studied in rabbits injected with preparations of HDL which had been labeled with 3H in the esterified and free cholesterol moieties. These labeled HDL preparations had been isolated either from the serum of donor rabbits which had been previously injected with 3H-mevalonic acid or from rabbit serum which had been incubated in vitro at 37 degrees with 3H-cholesterol. In terms of subsequent in vivo metabolism, there were no significant differences between the in vivo labeled and in vitro labeled HDL preparations. It was also found that the presence of free 3H-cholesterol in the injected HDL had very little effect on the recipient esterified 3H-cholesterol results. The removal of esterified 3H-cholesterol from the recipient HDL fraction was biphasic, with the initial phase largely reflecting a transfer into the plasma VLDL and LDL fractions rather than a removal from the plasma compartment. In fact, the initial rate of removal from HDL was very much influenced by the distribution of esterified cholesterol mass in the different lipoprotein fractions; the greater the proportion in VLDL and LDL, the more rapid was the initial rate of removal from HDL. A transfer of esterified cholesterol from HDL to VLDL and LDL was estimated to be of the order of 150 to 200 mumol/L of plasma per hour, a value much greater than the reported rate of production of esterified cholesterol in rabbit plasma. The implication that such transfers might therefore have been partially reversible was confirmed in in vitro incubations of labeled HDL and unlabeled rabbit serum."}
{"id": "PMID:219122", "title": "Generation of superoxide radicals by human peripheral neutrophils activated by chemotactic factor. Evidence for the role of calcium.", "content": "In response to activation by the synthetic chemotactic factor FMLP, human peripheral neutrophils generated superoxide radicals as assessed by ferricytochrome C reduction. A dose-dependent increase in the amount of superoxide induced by FMLP over the concentration range of 1 X 10(-8) M to 1.6 X 10(-7) M was observed. Examination of the kinetics of the response revealed large amounts of superoxide generated by 1 min of incubation at 37 degrees C at an optimal dose of FMLP and a plateau effect after 5 min of incubation. Divalent cations did not influence the binding of 3H-FMLP to the cell, but superoxide generation by FMLP-activated neutrophils was observed to be dependent on the presence of divalent cations in the medium. In the absence of Mg2+, increasing Ca2+ ion concentration in the medium led to progressive increases in superoxide generation up to 4 mM, after which the response declined slightly. Mg2+, 0.25 to 4 mM, increased FMLP-induced superoxide generation to a much lower extent than did Ca2+. Lanthanum ion, 0.1 to 1 mM, in the presence of 1 mM Ca2+ inhibited the production of superoxide by FMLP 4 X 10(-8 ) M. Over the concentration range 3.3 X 10(-5 M to 3 X 10(-4 M, verapamil, a drug which selectively blocks the calcium channel, caused a dose-dependent inhibition of superoxide production and calcium-45 uptake in response to FMLP. This effect of verapamil could be overcome by increasing the concentration of Ca2+ in the medium. These observations suggest that a calcium influx plays an important role in the superoxide-generating capacity of the neutrophil.", "contents": "Generation of superoxide radicals by human peripheral neutrophils activated by chemotactic factor. Evidence for the role of calcium. In response to activation by the synthetic chemotactic factor FMLP, human peripheral neutrophils generated superoxide radicals as assessed by ferricytochrome C reduction. A dose-dependent increase in the amount of superoxide induced by FMLP over the concentration range of 1 X 10(-8) M to 1.6 X 10(-7) M was observed. Examination of the kinetics of the response revealed large amounts of superoxide generated by 1 min of incubation at 37 degrees C at an optimal dose of FMLP and a plateau effect after 5 min of incubation. Divalent cations did not influence the binding of 3H-FMLP to the cell, but superoxide generation by FMLP-activated neutrophils was observed to be dependent on the presence of divalent cations in the medium. In the absence of Mg2+, increasing Ca2+ ion concentration in the medium led to progressive increases in superoxide generation up to 4 mM, after which the response declined slightly. Mg2+, 0.25 to 4 mM, increased FMLP-induced superoxide generation to a much lower extent than did Ca2+. Lanthanum ion, 0.1 to 1 mM, in the presence of 1 mM Ca2+ inhibited the production of superoxide by FMLP 4 X 10(-8 ) M. Over the concentration range 3.3 X 10(-5 M to 3 X 10(-4 M, verapamil, a drug which selectively blocks the calcium channel, caused a dose-dependent inhibition of superoxide production and calcium-45 uptake in response to FMLP. This effect of verapamil could be overcome by increasing the concentration of Ca2+ in the medium. These observations suggest that a calcium influx plays an important role in the superoxide-generating capacity of the neutrophil."}
{"id": "PMID:219123", "title": "The effect of homologous thrombin and fibrinogen degradation products on fibrinogen synthesis in rabbits.", "content": "The effect of intravenous infusions of purified homologous FDP and thrombin on fibrinogen synthesis was evaluated in rabbits. De novo fibrinogen production was measured by the rate of incorporation of 75SeM into circulating fibrinogen. After receiving either 100 or 200 NIH U/kg purified homologous thrombin over 1 hr, rabbits demonstrated threefold and fivefold increases in fibrinogen synthesis, respectively. A correlation between the titers of FDP-fdp and the degree of fibrinogen synthesis was evident. Prior administration of epsilon-ACA prevented the accelerated synthesis of fibrinogen induced by thrombin and inhibited the appearance of FDP-fdp in serum. epsilon-ACA did not interfere with normal fibrinogen production. Fibrinogen synthesis was assessed following infusions of FDP prepared by vitro by digestion of rabbit fibrinogen with plasmin and subsequently identified on SDS-polyacrylamide gels. Preparations which contained predominantly stage 2 intermediate (X, Y, D, and E) or stage 3 final (D and E) fragments accelerated fibrinogen synthesis, whereas those containing predominantly stage 1 fragment X did not. Prior treatment with epsilon-ACA did not alter these results. Infusion of the supernatants derived from immunoprecipitation of the FDP by either anti-rabbit fibrinogen antibody or specific anti-human D and E antibodies significantly diminished the enhanced fibrinogen synthesis induced by the unadsorbed materials. These experiments suggest that the accelerated fibrinogen synthesis induced by thrombin is mediated by FDP, with fragments D and E appearing to be the most potent.", "contents": "The effect of homologous thrombin and fibrinogen degradation products on fibrinogen synthesis in rabbits. The effect of intravenous infusions of purified homologous FDP and thrombin on fibrinogen synthesis was evaluated in rabbits. De novo fibrinogen production was measured by the rate of incorporation of 75SeM into circulating fibrinogen. After receiving either 100 or 200 NIH U/kg purified homologous thrombin over 1 hr, rabbits demonstrated threefold and fivefold increases in fibrinogen synthesis, respectively. A correlation between the titers of FDP-fdp and the degree of fibrinogen synthesis was evident. Prior administration of epsilon-ACA prevented the accelerated synthesis of fibrinogen induced by thrombin and inhibited the appearance of FDP-fdp in serum. epsilon-ACA did not interfere with normal fibrinogen production. Fibrinogen synthesis was assessed following infusions of FDP prepared by vitro by digestion of rabbit fibrinogen with plasmin and subsequently identified on SDS-polyacrylamide gels. Preparations which contained predominantly stage 2 intermediate (X, Y, D, and E) or stage 3 final (D and E) fragments accelerated fibrinogen synthesis, whereas those containing predominantly stage 1 fragment X did not. Prior treatment with epsilon-ACA did not alter these results. Infusion of the supernatants derived from immunoprecipitation of the FDP by either anti-rabbit fibrinogen antibody or specific anti-human D and E antibodies significantly diminished the enhanced fibrinogen synthesis induced by the unadsorbed materials. These experiments suggest that the accelerated fibrinogen synthesis induced by thrombin is mediated by FDP, with fragments D and E appearing to be the most potent."}
{"id": "PMID:219124", "title": "Validation of a recording spectrophotometric method for measurement of membrane-associated Mg- and NaK-ATPase activity.", "content": "Conventional methods for determination of membrane-associated Mg- and NaK-ATPase activity typically involve a timed incubation of enzyme with ATP followed by measurement of released Pi. They are time-consuming, require a large amount of enzyme protein, and show considerable variability induplicate samples. These problems can be largely eliminated with a coupled enzyme assay in which formation of ADP by ATPase is coupled to NADH oxidation with the intermediate enzymes PK and LDH and the intermediate substrate phosphoenolpyruvate present in excess. NADH oxidation is continuously recorded at 340 nm, and NaK-ATPase represents the ouabain suppressible fraction of total ATPase. This method allows accurate determinatin of initial reaction rates which vary linearly with respect to enzyme protein. Furthermore, it eliminates the need to measure Pi and prevents accumulation of inhibitory ADP. In over 100 preparations of LPM prepared from rats pretreated with agents known to alter ATPase activity or exposed in vitro to ATPase inhibitors. ATPase activity by the coupled-enzyme assay paralleled results obtained with the conventional method. Moreover, the coupled-enzyme assay required less membrane protein, showed less variability in duplicate samples, required half the time, and also yielded accurate values in brain, kidney, and heart tissue. This improved assay should find broad application in the study of membrane ATPase as they relate to a variety of cellular functions.", "contents": "Validation of a recording spectrophotometric method for measurement of membrane-associated Mg- and NaK-ATPase activity. Conventional methods for determination of membrane-associated Mg- and NaK-ATPase activity typically involve a timed incubation of enzyme with ATP followed by measurement of released Pi. They are time-consuming, require a large amount of enzyme protein, and show considerable variability induplicate samples. These problems can be largely eliminated with a coupled enzyme assay in which formation of ADP by ATPase is coupled to NADH oxidation with the intermediate enzymes PK and LDH and the intermediate substrate phosphoenolpyruvate present in excess. NADH oxidation is continuously recorded at 340 nm, and NaK-ATPase represents the ouabain suppressible fraction of total ATPase. This method allows accurate determinatin of initial reaction rates which vary linearly with respect to enzyme protein. Furthermore, it eliminates the need to measure Pi and prevents accumulation of inhibitory ADP. In over 100 preparations of LPM prepared from rats pretreated with agents known to alter ATPase activity or exposed in vitro to ATPase inhibitors. ATPase activity by the coupled-enzyme assay paralleled results obtained with the conventional method. Moreover, the coupled-enzyme assay required less membrane protein, showed less variability in duplicate samples, required half the time, and also yielded accurate values in brain, kidney, and heart tissue. This improved assay should find broad application in the study of membrane ATPase as they relate to a variety of cellular functions."}
{"id": "PMID:219125", "title": "Influence of cationic local anesthetics on the metabolism and ultrastructure of human alveolar macrophages.", "content": "The concentrations of cationic local anesthetics present in effluents from subsegmental bronchoscopic lavage were determined. Subsequently, the effect of these agents on lavaged human AM was evaluated in vitro. The results indicate that concentrations of LDC that may alter human AM function are present in effluents during routine subsegmental bronchopulmonary lavage. LDC and TRC in a dose-dependent fashion rapidly inhibited oxygen consumption and superoxide anion (O-2.) release by unstimulated human AM or AM stimulated by bacteria or the membrane-active chemical PMA. Concentrations of 2 mM TRC or 16 mM LDC reduced O2 consumption and O-2. release by unstimulated AM by more than 70% and blocked the usual spurt in O2 uptake and O-2. release observed for stimulated AM. This inhibition was not due to cytotoxicity, since washing n a balanced salt solution restored the metabolic function of treated AM. TRC or LDC also had effects on the morphology of washed human AM, causing rounding of the cell surface (scanning electron microscopy). In summary, the findings show that anesthetic agents routinely present in lavage effluents have the capacity to alter the function and structure of human AM. Although the effect must be considered in the design and interpretation of studies using AM obtained by bronchopulmonary lavage, the cationic anesthetics may also prove to be valuable agents for evaluating cell membrane-related events of human AM.", "contents": "Influence of cationic local anesthetics on the metabolism and ultrastructure of human alveolar macrophages. The concentrations of cationic local anesthetics present in effluents from subsegmental bronchoscopic lavage were determined. Subsequently, the effect of these agents on lavaged human AM was evaluated in vitro. The results indicate that concentrations of LDC that may alter human AM function are present in effluents during routine subsegmental bronchopulmonary lavage. LDC and TRC in a dose-dependent fashion rapidly inhibited oxygen consumption and superoxide anion (O-2.) release by unstimulated human AM or AM stimulated by bacteria or the membrane-active chemical PMA. Concentrations of 2 mM TRC or 16 mM LDC reduced O2 consumption and O-2. release by unstimulated AM by more than 70% and blocked the usual spurt in O2 uptake and O-2. release observed for stimulated AM. This inhibition was not due to cytotoxicity, since washing n a balanced salt solution restored the metabolic function of treated AM. TRC or LDC also had effects on the morphology of washed human AM, causing rounding of the cell surface (scanning electron microscopy). In summary, the findings show that anesthetic agents routinely present in lavage effluents have the capacity to alter the function and structure of human AM. Although the effect must be considered in the design and interpretation of studies using AM obtained by bronchopulmonary lavage, the cationic anesthetics may also prove to be valuable agents for evaluating cell membrane-related events of human AM."}
{"id": "PMID:219127", "title": "Inhibition of aldosterone production in adrenal cell suspensions by serum from patients with manic-depressive psychosis.", "content": "A method of preparing a suspension of cells of the zona glomerulosa from rat adrenal capsules treated with crude collagenase is described. The cells responded to ACTH, angiotensin II and serotonin by increased production of aldosterone. Pooled human sera or individual human sera (from healthy normal or non-psychiatric in-patients) to a final concentration of 30% had no effect on ACTH-stimulated production of aldosterone. Many serum samples from five patients with manic-depressive psychosis, however, caused a reduction in aldosterone production; 65% of those samples taken during depression, 44% of the samples taken during manic episodes and 23% of the samples taken when the mood was normal. Sera from manic-depressive patients also reduced the production of aldosterone caused by angiotensin II or serotonin. This effect of serum from manic-depressives in vitro may be related to the abnormalities of aldosterone control in such patients.", "contents": "Inhibition of aldosterone production in adrenal cell suspensions by serum from patients with manic-depressive psychosis. A method of preparing a suspension of cells of the zona glomerulosa from rat adrenal capsules treated with crude collagenase is described. The cells responded to ACTH, angiotensin II and serotonin by increased production of aldosterone. Pooled human sera or individual human sera (from healthy normal or non-psychiatric in-patients) to a final concentration of 30% had no effect on ACTH-stimulated production of aldosterone. Many serum samples from five patients with manic-depressive psychosis, however, caused a reduction in aldosterone production; 65% of those samples taken during depression, 44% of the samples taken during manic episodes and 23% of the samples taken when the mood was normal. Sera from manic-depressive patients also reduced the production of aldosterone caused by angiotensin II or serotonin. This effect of serum from manic-depressives in vitro may be related to the abnormalities of aldosterone control in such patients."}
{"id": "PMID:219128", "title": "Comparison of the stimulatory effects of ovine, porcine and human follicle-stimulating hormone and of ovine and human luteinizing hormone on the accumulation of cyclic AMP by porcine granulosa cells.", "content": "The effects of ovine, porcine and human FSH, and ovine and human LH on the accumulation of cyclic AMP by porcine granulosa cells obtained from follicles at various stages of maturation were investigated. During incubation periods of 15 min, 10 micrograms ovine FSH pretreated with antiserum to LH or 10 micrograms human FSH resulted in an 11- to 18-fold, five- to ninefold, and less than a twofold increase in intracellular accumulation of cyclic AMP by granulosa cells from small (1--2 mm), medium (3--5 mm) and large (6--12 mm) follicles respectively. Similar patterns of response occurred with addition of porcine FSH. After incubation for 30 and 60 min with ovine, porcine or human FSH, significant accumulation of cyclic AMP in the incubation medium occurred with cells obtained from small and medium-sized follicles. After 60 min of incubation with FSH the accumulation of cyclic AMP in the incubation medium exceeded the intracellular cyclic AMP levels in granulosa cells from small and medium-sized follicles. During incubation periods of 15 min, 1.0 micrograms ovine LH resulted in less than a twofold, a fourfold and greater than a tenfold increase in intracellular accumulation of cyclic AMP by granulosa cells from small, medium and large follicles respectively. Addition of human LH brought about a similar response. Incubation periods of 30 and 60 min with 1.0 micrograms ovine or human LH resulted in significant accumulation of cyclic AMP in the incubation medium by granulosa cells from large follicles; cyclic AMP content in the incubation medium was greater after 60 min compared with 30 min of incubation. It was concluded that ovine FSH pretreated with an antiserum to LH had similar effects on cyclic AMP levels as did purified human and porcine FSH, and that the stimulatory effects of the less pure ovine FSH were probably not due to an impurity in the FSH preparation. Porcine granulosa cells obtained from small follicles should be suitable as an in-vitro FSH bioassay while granulosa cells obtained from large follicles should be suitable as an in-vitro LH bioassay.", "contents": "Comparison of the stimulatory effects of ovine, porcine and human follicle-stimulating hormone and of ovine and human luteinizing hormone on the accumulation of cyclic AMP by porcine granulosa cells. The effects of ovine, porcine and human FSH, and ovine and human LH on the accumulation of cyclic AMP by porcine granulosa cells obtained from follicles at various stages of maturation were investigated. During incubation periods of 15 min, 10 micrograms ovine FSH pretreated with antiserum to LH or 10 micrograms human FSH resulted in an 11- to 18-fold, five- to ninefold, and less than a twofold increase in intracellular accumulation of cyclic AMP by granulosa cells from small (1--2 mm), medium (3--5 mm) and large (6--12 mm) follicles respectively. Similar patterns of response occurred with addition of porcine FSH. After incubation for 30 and 60 min with ovine, porcine or human FSH, significant accumulation of cyclic AMP in the incubation medium occurred with cells obtained from small and medium-sized follicles. After 60 min of incubation with FSH the accumulation of cyclic AMP in the incubation medium exceeded the intracellular cyclic AMP levels in granulosa cells from small and medium-sized follicles. During incubation periods of 15 min, 1.0 micrograms ovine LH resulted in less than a twofold, a fourfold and greater than a tenfold increase in intracellular accumulation of cyclic AMP by granulosa cells from small, medium and large follicles respectively. Addition of human LH brought about a similar response. Incubation periods of 30 and 60 min with 1.0 micrograms ovine or human LH resulted in significant accumulation of cyclic AMP in the incubation medium by granulosa cells from large follicles; cyclic AMP content in the incubation medium was greater after 60 min compared with 30 min of incubation. It was concluded that ovine FSH pretreated with an antiserum to LH had similar effects on cyclic AMP levels as did purified human and porcine FSH, and that the stimulatory effects of the less pure ovine FSH were probably not due to an impurity in the FSH preparation. Porcine granulosa cells obtained from small follicles should be suitable as an in-vitro FSH bioassay while granulosa cells obtained from large follicles should be suitable as an in-vitro LH bioassay."}
{"id": "PMID:219129", "title": "Regulation of specific cell-mediated cytotoxic response against SV40-induced tumor associated antigens by depletion of suppressor T cells with cyclophosphamide in mice.", "content": "When cyclophosphamide was administered to mice before immunization with syngeneic SV40 transformed cells, the specific immune response elicited, as was measured by in vitro 51Cr release assay was stronger and lasted longer when compared to the response generated in noncyclophosphamide-treated mice. The augmentation effect of the drug was dependent on cyclophosphamide concentration being optimal at 100 mg/kg and on the time of drug administration in relation to antigen immunization being optimal at 2 d before antigen administration. Transfer of T cells from normal syngeneic mice to drug-treated animals abolished the cyclophosphamide-induced augmentation of immune response. These results implied that cyclophosphamide sensitive T cells suppressed the in vivo generation of specific effector T cells against SV40-induced tumor-associated antigens.", "contents": "Regulation of specific cell-mediated cytotoxic response against SV40-induced tumor associated antigens by depletion of suppressor T cells with cyclophosphamide in mice. When cyclophosphamide was administered to mice before immunization with syngeneic SV40 transformed cells, the specific immune response elicited, as was measured by in vitro 51Cr release assay was stronger and lasted longer when compared to the response generated in noncyclophosphamide-treated mice. The augmentation effect of the drug was dependent on cyclophosphamide concentration being optimal at 100 mg/kg and on the time of drug administration in relation to antigen immunization being optimal at 2 d before antigen administration. Transfer of T cells from normal syngeneic mice to drug-treated animals abolished the cyclophosphamide-induced augmentation of immune response. These results implied that cyclophosphamide sensitive T cells suppressed the in vivo generation of specific effector T cells against SV40-induced tumor-associated antigens."}
{"id": "PMID:219130", "title": "A role for elevated H-2 antigen expression in resistance to neoplasia caused by radiation-induced leukemia virus. Enhancement of effective tumor surveillance by killer lymphocytes.", "content": "Resistance to neoplasia caused by radiation-induced leukemia virus (RadLV) is mediated by gene(s) in the H-2D region of the major histocompatibility complex. The previous observation that rapid increases in cellular synthesis and cell-surface expression of H-2 antigens are detectable immediately after virus inoculation has suggested that altered expression of H-2 antigens may play a significant role in the mechanism(s) of host defense to virus infection. This concept is supported by the following observations. First, cell-mediated immunity against RadLV transformed or infected cells can be detected with ease when H-2-positive target cells are used in the cell-mediated lympholysis (CML) assay. (Although RadLV transformed cells obtained from overtly leukemic animals and maintained in tissue culture are H-2 negative, these cells can regain their H-2 phenotype by in vivo passage in normal animals. The H-2-negative cells are poor targets in a CML assay.) Second, resistant mice develop greater numbers of effectors when infected with RadLV than do susceptible mice. Third, injection of normal (uninfected) thymocytes into syngeneic recipients of resistant or susceptible H-2 type does not stimulate a CML response. However, injection of RadLV infected thymocytes from resistant mice produces a vigorous CMI response, and such thymocytes elicit the strongest response at a time when both H-2 and viral antigen expression is elevated. By contrast, injection of infected thymocytes from susceptible mice, which express viral antigens, but low levels of H-2 antigens, does not stimulate a CML reaction. These findings may explain the easier induction of leukemia found by many investigators when virus is inoculated into neonatal mice and the preferential thymus tropism of some oncogenic type-C RNA virus. Cells expressing very low levels of H-2, such as thymocytes, may serve as permissive targets for virus infection because they lack an important component (H-2 antigens) of the dual or altered recognition signal required to trigger a defensive host immune response.", "contents": "A role for elevated H-2 antigen expression in resistance to neoplasia caused by radiation-induced leukemia virus. Enhancement of effective tumor surveillance by killer lymphocytes. Resistance to neoplasia caused by radiation-induced leukemia virus (RadLV) is mediated by gene(s) in the H-2D region of the major histocompatibility complex. The previous observation that rapid increases in cellular synthesis and cell-surface expression of H-2 antigens are detectable immediately after virus inoculation has suggested that altered expression of H-2 antigens may play a significant role in the mechanism(s) of host defense to virus infection. This concept is supported by the following observations. First, cell-mediated immunity against RadLV transformed or infected cells can be detected with ease when H-2-positive target cells are used in the cell-mediated lympholysis (CML) assay. (Although RadLV transformed cells obtained from overtly leukemic animals and maintained in tissue culture are H-2 negative, these cells can regain their H-2 phenotype by in vivo passage in normal animals. The H-2-negative cells are poor targets in a CML assay.) Second, resistant mice develop greater numbers of effectors when infected with RadLV than do susceptible mice. Third, injection of normal (uninfected) thymocytes into syngeneic recipients of resistant or susceptible H-2 type does not stimulate a CML response. However, injection of RadLV infected thymocytes from resistant mice produces a vigorous CMI response, and such thymocytes elicit the strongest response at a time when both H-2 and viral antigen expression is elevated. By contrast, injection of infected thymocytes from susceptible mice, which express viral antigens, but low levels of H-2 antigens, does not stimulate a CML reaction. These findings may explain the easier induction of leukemia found by many investigators when virus is inoculated into neonatal mice and the preferential thymus tropism of some oncogenic type-C RNA virus. Cells expressing very low levels of H-2, such as thymocytes, may serve as permissive targets for virus infection because they lack an important component (H-2 antigens) of the dual or altered recognition signal required to trigger a defensive host immune response."}
{"id": "PMID:219131", "title": "Normal functional characteristics of cultured human promyelocytic leukemia cells (HL-60) after induction of differentiation by dimethylsulfoxide.", "content": "The HL-60 human promyelocytic leukemia cell line can be induced to terminally differentiate to mature myeloid cells sharing a number of functional characteristics with normal granulocytes including response to chemoattractants, development of complement receptors, phagocytosis, superoxide production, and nitroblue tetrazolium dye reduction. Hence the Me2SO-induced HL-60 cells provide a unique in vitro model for studying various important aspects of human myeloid cell differentiation.", "contents": "Normal functional characteristics of cultured human promyelocytic leukemia cells (HL-60) after induction of differentiation by dimethylsulfoxide. The HL-60 human promyelocytic leukemia cell line can be induced to terminally differentiate to mature myeloid cells sharing a number of functional characteristics with normal granulocytes including response to chemoattractants, development of complement receptors, phagocytosis, superoxide production, and nitroblue tetrazolium dye reduction. Hence the Me2SO-induced HL-60 cells provide a unique in vitro model for studying various important aspects of human myeloid cell differentiation."}
{"id": "PMID:219132", "title": "The family and cardiac rehabilitation.", "content": "Family resources and needs are often overlooked in planning for rehabilitation of the individual following myocardial infarction. The acute ischemic event presents a massive disruption in the psychodynamic balance of the family, but it can provide an unparalleled opportunity for increased awareness and growth for all members of the family. An integrated program of emotional support, education, and physical activity is recommended to facilitate restoration of the individual's self-esteem. Formal family counseling provides a forum for resolution of fears and misconceptions and permits redefinition of roles within the family.", "contents": "The family and cardiac rehabilitation. Family resources and needs are often overlooked in planning for rehabilitation of the individual following myocardial infarction. The acute ischemic event presents a massive disruption in the psychodynamic balance of the family, but it can provide an unparalleled opportunity for increased awareness and growth for all members of the family. An integrated program of emotional support, education, and physical activity is recommended to facilitate restoration of the individual's self-esteem. Formal family counseling provides a forum for resolution of fears and misconceptions and permits redefinition of roles within the family."}
{"id": "PMID:219135", "title": "Relationship between virus neutralization and serum protection bioassays for IgG and IgM antibodies to foot-and-mouth disease virus.", "content": "The time interval between administering the serum and the virus was found to influence the results of the in vivo mouse protection test for foot-and-mouth disease antibodies. In particular, for both IgG and IgM antibodies to strain A12 virus, the mouse protection index increased from zero to a maximum at about 6 h and remained high for at least five days. Variations in the antiserum concentration, on a log scale, had a proportional effect on the mouse protection index, if between 1 and 3. The constant of proportionality was unity for IgM and 2 for IgG antibody. Comparison with in vitro neutralization tests revealed essentially parallel neutralization curves. The lower serum titre in the protection test, if computed for less than 10(3) LD50/dose, was accounted for by the simple dilution of the inoculated serum into the volume of the mouse. Consequently, in the low titre range, the same virus-antibody reaction and its effect are operable in each of the two tests. Analysis of literature data in which both the in vivo protection test and the in vitro neutralization test results were available on the same sera showed consistency with the above conclusions for both cattle and swine sera. The protection test had a highly atypical survival pattern occurring at antibody concentrations expected to neutralize more than 10(3) LD50/dose. The resulting in vivo dampening effect on virus titre is postulated to be caused by the excess antibody of the passive immunity test interfering with the spread of infection. The effect is analogous to an anomaly caused by not removing the inoculum in quantal tissue culture assays and it prevents quantification of antibody levels in strong sera.", "contents": "Relationship between virus neutralization and serum protection bioassays for IgG and IgM antibodies to foot-and-mouth disease virus. The time interval between administering the serum and the virus was found to influence the results of the in vivo mouse protection test for foot-and-mouth disease antibodies. In particular, for both IgG and IgM antibodies to strain A12 virus, the mouse protection index increased from zero to a maximum at about 6 h and remained high for at least five days. Variations in the antiserum concentration, on a log scale, had a proportional effect on the mouse protection index, if between 1 and 3. The constant of proportionality was unity for IgM and 2 for IgG antibody. Comparison with in vitro neutralization tests revealed essentially parallel neutralization curves. The lower serum titre in the protection test, if computed for less than 10(3) LD50/dose, was accounted for by the simple dilution of the inoculated serum into the volume of the mouse. Consequently, in the low titre range, the same virus-antibody reaction and its effect are operable in each of the two tests. Analysis of literature data in which both the in vivo protection test and the in vitro neutralization test results were available on the same sera showed consistency with the above conclusions for both cattle and swine sera. The protection test had a highly atypical survival pattern occurring at antibody concentrations expected to neutralize more than 10(3) LD50/dose. The resulting in vivo dampening effect on virus titre is postulated to be caused by the excess antibody of the passive immunity test interfering with the spread of infection. The effect is analogous to an anomaly caused by not removing the inoculum in quantal tissue culture assays and it prevents quantification of antibody levels in strong sera."}
{"id": "PMID:219136", "title": "Isolation and characterization of BK virus-transformed rat and mouse cells.", "content": "The isolation and characterization of four groups of BK virus (BKV)-transformed rat embryo fibroblast (RE) and mouse kidney (MK) cells are described. They consist of (1) seven RE lines transformed with a BKV pool containing a high proportion of defective virions, and (2) 16 RE, (3) 14 Balb/c-MK and (4) 2 Swiss ICR-MK lines, all transformed, at different input multiplicities, with a pool of BKV free of defective virions. None of the lines produces BKV, all contain BKV T antigen and all grow to higher saturation densities and have higher plating efficiencies than do the corresponding control cells. Cells of the RE lines, transformed with the BKV pool containing defective virions, form colonies in soft agar and produce tumours in irradiated weanling rats, while those of the RE lines transformed with the defective virion-free pool do neither. Cells of the Balb/c-MK, but not of the ICR-MK lines are tumorigenic, although cells of both groups form colonies in soft agar. In general, those lines transformed at higher multiplicities express the biological properties associated with transformation more strongly than do those transformed at lower multiplicities.", "contents": "Isolation and characterization of BK virus-transformed rat and mouse cells. The isolation and characterization of four groups of BK virus (BKV)-transformed rat embryo fibroblast (RE) and mouse kidney (MK) cells are described. They consist of (1) seven RE lines transformed with a BKV pool containing a high proportion of defective virions, and (2) 16 RE, (3) 14 Balb/c-MK and (4) 2 Swiss ICR-MK lines, all transformed, at different input multiplicities, with a pool of BKV free of defective virions. None of the lines produces BKV, all contain BKV T antigen and all grow to higher saturation densities and have higher plating efficiencies than do the corresponding control cells. Cells of the RE lines, transformed with the BKV pool containing defective virions, form colonies in soft agar and produce tumours in irradiated weanling rats, while those of the RE lines transformed with the defective virion-free pool do neither. Cells of the Balb/c-MK, but not of the ICR-MK lines are tumorigenic, although cells of both groups form colonies in soft agar. In general, those lines transformed at higher multiplicities express the biological properties associated with transformation more strongly than do those transformed at lower multiplicities."}
{"id": "PMID:219137", "title": "Detection and quantification of foot and mouth disease virus by enzyme labelled immunosorbent assay techniques.", "content": "Enzyme labelled immunosorbent assays (ELISA) have been developed to detect and quantify foot and mouth disease (FMD) virus using flexible plastic microtitre plates. The methods were successful for the specific detection of FMD virus and were 50 to 100 times more sensitive than the complement fixation test. The application of the ELISA techniques to FMD virus typing and subtyping, and to the assay of antigen concentration during manufacture of vaccines is discussed.", "contents": "Detection and quantification of foot and mouth disease virus by enzyme labelled immunosorbent assay techniques. Enzyme labelled immunosorbent assays (ELISA) have been developed to detect and quantify foot and mouth disease (FMD) virus using flexible plastic microtitre plates. The methods were successful for the specific detection of FMD virus and were 50 to 100 times more sensitive than the complement fixation test. The application of the ELISA techniques to FMD virus typing and subtyping, and to the assay of antigen concentration during manufacture of vaccines is discussed."}
{"id": "PMID:219138", "title": "Virus carrier state suppresses tumorigenicity of tumor cells in athymic (nude) mice.", "content": "Nude mice injected subcutaneously with normal uninfected BHK 21 cells or HeLa cells regularly develop large, rapidly-growing tumours at the subcutaneous site of inoculation. However, these same tumour cell lines when persistently infected with VSV or other enveloped RNA viruses are either rejected or form small nodules in nude mice. This rejection phenomenon probably involves some type of immunocyte since heavily-irradiated nude mice (500 rads) cannot reject persistently infected cells but develop large, rapidly-growing tumours which shed virus and defective interfering virus (DI) and which do not exhibit the lymphocytic infiltration observed in the nodules of unirradiated mice given persistently infected cells. Finally, it was possible to select a subline of BHK 21-VSV carrier cells which regularly produces large rapidly-growing tumours in normal unirradiated nude mice, although all these carrier cells express virus antigen and shed large amounts of mature infectious virus and DI both in vivo and in vitro.", "contents": "Virus carrier state suppresses tumorigenicity of tumor cells in athymic (nude) mice. Nude mice injected subcutaneously with normal uninfected BHK 21 cells or HeLa cells regularly develop large, rapidly-growing tumours at the subcutaneous site of inoculation. However, these same tumour cell lines when persistently infected with VSV or other enveloped RNA viruses are either rejected or form small nodules in nude mice. This rejection phenomenon probably involves some type of immunocyte since heavily-irradiated nude mice (500 rads) cannot reject persistently infected cells but develop large, rapidly-growing tumours which shed virus and defective interfering virus (DI) and which do not exhibit the lymphocytic infiltration observed in the nodules of unirradiated mice given persistently infected cells. Finally, it was possible to select a subline of BHK 21-VSV carrier cells which regularly produces large rapidly-growing tumours in normal unirradiated nude mice, although all these carrier cells express virus antigen and shed large amounts of mature infectious virus and DI both in vivo and in vitro."}
{"id": "PMID:219139", "title": "Impairment of hormone dependent signal transfer by chronic SSPE virus infection.", "content": "In a CNS-derived cell line, the cellular response to hormonal stimulation, represented by the rise of intracellular cAMP levels, is impaired under the influence of a persisting neurotropic virus infection. This dysfunction is caused by the decrease in adenylate cyclase activity, most probably due to the virus-induced loss of active catalytic units.", "contents": "Impairment of hormone dependent signal transfer by chronic SSPE virus infection. In a CNS-derived cell line, the cellular response to hormonal stimulation, represented by the rise of intracellular cAMP levels, is impaired under the influence of a persisting neurotropic virus infection. This dysfunction is caused by the decrease in adenylate cyclase activity, most probably due to the virus-induced loss of active catalytic units."}
{"id": "PMID:219140", "title": "Vertical transmission of murine cytomegalovirus.", "content": "Congenital abnormalities induced by murine cytomegalovirus have previously been suggested to be an indirect effect of maternal illness as no infectious virus has been isolated from the foetus. However, in this article we report that latent virus detectable by immunofluorescence and in situ hybridization, may frequently be present in foetal tissues.", "contents": "Vertical transmission of murine cytomegalovirus. Congenital abnormalities induced by murine cytomegalovirus have previously been suggested to be an indirect effect of maternal illness as no infectious virus has been isolated from the foetus. However, in this article we report that latent virus detectable by immunofluorescence and in situ hybridization, may frequently be present in foetal tissues."}
{"id": "PMID:219141", "title": "Rabies virus infection selectively impairs membrane receptor functions in neuronal model cells.", "content": "A persistent infection with rabies virus (HEP-Flury) was established in the CNS-derived hybrid cell line 108CC15 which possesses specific membrane receptors for prostaglandins, catecholamines and acetylcholine. We report a differential virus influence on the specific receptor response to PGE, isoproterenol and acetycholine as indicated by typical changes of the intracellular cyclic AMP levels. As the adenylate cyclase activity was unchanged in infected cells in vitro, a selective virus influence on specific receptors themselves or their coupling to the cAMP synthesizing system must be considered.", "contents": "Rabies virus infection selectively impairs membrane receptor functions in neuronal model cells. A persistent infection with rabies virus (HEP-Flury) was established in the CNS-derived hybrid cell line 108CC15 which possesses specific membrane receptors for prostaglandins, catecholamines and acetylcholine. We report a differential virus influence on the specific receptor response to PGE, isoproterenol and acetycholine as indicated by typical changes of the intracellular cyclic AMP levels. As the adenylate cyclase activity was unchanged in infected cells in vitro, a selective virus influence on specific receptors themselves or their coupling to the cAMP synthesizing system must be considered."}
{"id": "PMID:219152", "title": "Fine structure of contrasting choroid plexus lesions caused by tertiary amines or cyclophosphamide.", "content": "Hydropic alterations of the fine structure of the choroid plexus epithelium following administration of three different tertiary amines to rats were compared with alterations produced by cyclophosphamide and with normal choroid plexus. Single doses of 2,7-bis(2-diethylamino)-ethoxy)-4-methyl-1,8-naphthyridine HCl or 2,6-di-(omega-dimethyl aminoethoxy)-pyridine produced dramatic accumulations of membrane-limited vacuoles. Multiple doses of 2,7-bis-(diethylaminoethoxy)fluoren-9-one HCl (tilorone) produced accumulations of dense cytoplasmic bodies in choroid epithelial cells in addition to the hydropic vacuoles. Differential responses to these agents suggested functional specialization or temporal variation in function among adjacent choroidal cells. Despite the occurrence of pronounced plasma exudation in the plexitis following cyclophosphamide treatment, there was no hydropic vacuolization.", "contents": "Fine structure of contrasting choroid plexus lesions caused by tertiary amines or cyclophosphamide. Hydropic alterations of the fine structure of the choroid plexus epithelium following administration of three different tertiary amines to rats were compared with alterations produced by cyclophosphamide and with normal choroid plexus. Single doses of 2,7-bis(2-diethylamino)-ethoxy)-4-methyl-1,8-naphthyridine HCl or 2,6-di-(omega-dimethyl aminoethoxy)-pyridine produced dramatic accumulations of membrane-limited vacuoles. Multiple doses of 2,7-bis-(diethylaminoethoxy)fluoren-9-one HCl (tilorone) produced accumulations of dense cytoplasmic bodies in choroid epithelial cells in addition to the hydropic vacuoles. Differential responses to these agents suggested functional specialization or temporal variation in function among adjacent choroidal cells. Despite the occurrence of pronounced plasma exudation in the plexitis following cyclophosphamide treatment, there was no hydropic vacuolization."}
{"id": "PMID:219153", "title": "Herpes simplex virus types 1 and 2 in organotypic cultures of mouse central and peripheral nervous system. 2. Electron microscopic observations of myelin degeneration.", "content": "Organotypic cultures of mouse spinal cord with attached dorsal root ganglia, which contain both central and peripheral myelin in the one unit of tissue, were infected with HSV 1 or HSV 2 and studied using electron microscopy. Intranuclear viral nucleocapsids and intracytoplasmic enveloped particles were found in the Schwann cells associated with peripheral myelin and in oligodendroglia associated with central myelin. Degeneration of peripheral myelin most commonly involved an asymmetrical swelling of the myelin lamellae, whereas degeneration of central myelin was characterized by a more generalized swelling resulting in separation of the myelin lamellae. Degeneration of both central and peripheral myelin was found in the presence of intact axons which were indistinguishable from those in controls.", "contents": "Herpes simplex virus types 1 and 2 in organotypic cultures of mouse central and peripheral nervous system. 2. Electron microscopic observations of myelin degeneration. Organotypic cultures of mouse spinal cord with attached dorsal root ganglia, which contain both central and peripheral myelin in the one unit of tissue, were infected with HSV 1 or HSV 2 and studied using electron microscopy. Intranuclear viral nucleocapsids and intracytoplasmic enveloped particles were found in the Schwann cells associated with peripheral myelin and in oligodendroglia associated with central myelin. Degeneration of peripheral myelin most commonly involved an asymmetrical swelling of the myelin lamellae, whereas degeneration of central myelin was characterized by a more generalized swelling resulting in separation of the myelin lamellae. Degeneration of both central and peripheral myelin was found in the presence of intact axons which were indistinguishable from those in controls."}
{"id": "PMID:219154", "title": "Cerebellar ganglioglioma in a child.", "content": "A cerebellar ganglioglioma was surgically removed from a two-year old boy, who had developed manifestations of increased intracranial pressure and cerebellar symptoms. At surgery, the tumor presented as a firm nodular mass displacing the cerebellar cortex. By light microscopy, its architecture differed distinctly from that of hamartomatous diffuse hypertrophy of the cerebellar cortex (Lhermitte-Duclos' disease). Mature ganglion cells were grouped in clusters and linked by thick bundles of nerve cell processes. Nerve cells and processes were enmeshed in a rich network of fibrillary connective tissue. Electron microscopy disclosed typical neuronal perikarya as well as numerous asymmetric chemical synapses. The bulk of the tumor consisted of tightly grouped, (non-myelinated) nerve cell processes arranged in parallel. One of the most prominent features of the tumor consisted of numerous dilatations of these processes. The largest ones contained microfilaments, while the smaller ones were entirely filled with dense bodies (most probably derived from degenerating mitochondria). Only scattered dense core vesicles were seen, which probably did not represent neurosecretory granules. A second cell type consisted probably of astrocytes. Most neuroepithelial cell processes could not be identified with certainty as being of either neuronal or glial origin. A third cell type consisted of numerous slender cells which were probably mesenchymal. They were surrounded by a network of basement membrane which extended between the surrounding nerve cell processes.", "contents": "Cerebellar ganglioglioma in a child. A cerebellar ganglioglioma was surgically removed from a two-year old boy, who had developed manifestations of increased intracranial pressure and cerebellar symptoms. At surgery, the tumor presented as a firm nodular mass displacing the cerebellar cortex. By light microscopy, its architecture differed distinctly from that of hamartomatous diffuse hypertrophy of the cerebellar cortex (Lhermitte-Duclos' disease). Mature ganglion cells were grouped in clusters and linked by thick bundles of nerve cell processes. Nerve cells and processes were enmeshed in a rich network of fibrillary connective tissue. Electron microscopy disclosed typical neuronal perikarya as well as numerous asymmetric chemical synapses. The bulk of the tumor consisted of tightly grouped, (non-myelinated) nerve cell processes arranged in parallel. One of the most prominent features of the tumor consisted of numerous dilatations of these processes. The largest ones contained microfilaments, while the smaller ones were entirely filled with dense bodies (most probably derived from degenerating mitochondria). Only scattered dense core vesicles were seen, which probably did not represent neurosecretory granules. A second cell type consisted probably of astrocytes. Most neuroepithelial cell processes could not be identified with certainty as being of either neuronal or glial origin. A third cell type consisted of numerous slender cells which were probably mesenchymal. They were surrounded by a network of basement membrane which extended between the surrounding nerve cell processes."}
{"id": "PMID:219155", "title": "Acoustic input to single neurons in pulvinar-posterior complex of cat thalamus.", "content": "1. Extracellular microelectrode recordings have been made of 429 single neurons in the pulvinar-posterior (Pul-PO) complex and adjacent regions of the thalamus of cats anesthetized with either sodium pentobarbital or alpha-chloralose. Controlled acoustic stimuli were presented by sealed systems incorporating probe microphone assemblies. 2. Neurons in pulvinar, lateralis posterior, and nucleus posterior were unresponsive to acoustic stimulation. Few cells in medial PO were observed to receive acoustic input, while sensitivity to tonal stimuli was a general feature of driven cells in other PO divisions. 3. Cells in lateral PO were generally sharply tuned to stimulus frequency, while the majority of cells in magnocellular medial geniculate and intermediate division of PO were broadly tuned. 4. Neurons in lateral PO and magnocellular medial geniculate had short response latencies to acoustic stimulation. Cells in intermediate division of PO were more often long latency. 5. Divisions of PO could not be differentiated on the basis of their binaural properties. Cells receiving excitatory input from solely the contralateral ear (E/O) or fros with onset discharge patterns showed occlusive binaural interaction properties. For cells with multiple-component discharge patterns, individual response components frequently had different patterns of binaural input and/or interaction. 6. On the basis of their discharge patterns, short latency, and frequency-tuning properties, it is suggested that lateral PO and magnocellular medial geniculate might derive their acoustic input from different divisions of the inferior colliculus. In contrast, the long latencies of units in PO intermediate division suggests a corticofugal input. 7. These data support anatomical parcelations of the Pul-PO complex, and the suggestion that this complex might provide acoustic input to the association cortices is evaluated.", "contents": "Acoustic input to single neurons in pulvinar-posterior complex of cat thalamus. 1. Extracellular microelectrode recordings have been made of 429 single neurons in the pulvinar-posterior (Pul-PO) complex and adjacent regions of the thalamus of cats anesthetized with either sodium pentobarbital or alpha-chloralose. Controlled acoustic stimuli were presented by sealed systems incorporating probe microphone assemblies. 2. Neurons in pulvinar, lateralis posterior, and nucleus posterior were unresponsive to acoustic stimulation. Few cells in medial PO were observed to receive acoustic input, while sensitivity to tonal stimuli was a general feature of driven cells in other PO divisions. 3. Cells in lateral PO were generally sharply tuned to stimulus frequency, while the majority of cells in magnocellular medial geniculate and intermediate division of PO were broadly tuned. 4. Neurons in lateral PO and magnocellular medial geniculate had short response latencies to acoustic stimulation. Cells in intermediate division of PO were more often long latency. 5. Divisions of PO could not be differentiated on the basis of their binaural properties. Cells receiving excitatory input from solely the contralateral ear (E/O) or fros with onset discharge patterns showed occlusive binaural interaction properties. For cells with multiple-component discharge patterns, individual response components frequently had different patterns of binaural input and/or interaction. 6. On the basis of their discharge patterns, short latency, and frequency-tuning properties, it is suggested that lateral PO and magnocellular medial geniculate might derive their acoustic input from different divisions of the inferior colliculus. In contrast, the long latencies of units in PO intermediate division suggests a corticofugal input. 7. These data support anatomical parcelations of the Pul-PO complex, and the suggestion that this complex might provide acoustic input to the association cortices is evaluated."}
{"id": "PMID:219156", "title": "Effects of stimulating in raphe nuclei and in reticular formation on response of spinothalamic neurons to mechanical stimuli.", "content": "1. The purpose of these experiments was to compare effects of electrical stimuli applied in two regions of the brain stem that are the sites of origin of descending bulbospinal systems; namely, the nucleus gigantocellularis of Brodal (7) and the nucleus raphe magnus, on the responses of lumbosacral spinothalamic neurons to mechanical stimuli. 2. In cats anesthetized with alpha-chloralose, stimulating in either of these structures with single pulses of current while the spinothalamic neuron was tonically activated by a sustained mechanical pressure resulted in an increase in the excitability of the cell followed by a prolonged suppression of its impulse activity. 3. For different neurons, the latency of the excitation ranged from 4 to 18 ms following the brain stem stimulus, while the latency of the suppression ranged from 16 to 34 ms. 4. In general, the effects of stimulating in the reticular formation and in the raphe nuclei were similar. although quantitative differences were found in the effects of each on different spinothalamic neurons. On the basis of these two studies, it is argued that the reticulospinal and raphe-spinal systems exert qualitatively similar effects on the responses of spinothalamic neurons evaluated in this experiment. 5. A comparison of the magnitudes of the suppression phase evoked from several different sites in the ipsilateral reticular formation and nucleus raphe magnus suggests that the descending systems arising from both these structures may be quite heterogeneous. 6. Stimulation of both regions of the brain stem produced a much greater suppression of the response of the spinothalamic neurons to slowly changing or sustained mechanical stimuli than to transient stimuli. It is suggested that the effects of descending systems arising both in the raphe nuclei and in the reticular formation on the responses of spinothalamic neurons to a mechanical stimulus are at least as dependent on the time course of the mechanical stimulus as they are on its intensity.", "contents": "Effects of stimulating in raphe nuclei and in reticular formation on response of spinothalamic neurons to mechanical stimuli. 1. The purpose of these experiments was to compare effects of electrical stimuli applied in two regions of the brain stem that are the sites of origin of descending bulbospinal systems; namely, the nucleus gigantocellularis of Brodal (7) and the nucleus raphe magnus, on the responses of lumbosacral spinothalamic neurons to mechanical stimuli. 2. In cats anesthetized with alpha-chloralose, stimulating in either of these structures with single pulses of current while the spinothalamic neuron was tonically activated by a sustained mechanical pressure resulted in an increase in the excitability of the cell followed by a prolonged suppression of its impulse activity. 3. For different neurons, the latency of the excitation ranged from 4 to 18 ms following the brain stem stimulus, while the latency of the suppression ranged from 16 to 34 ms. 4. In general, the effects of stimulating in the reticular formation and in the raphe nuclei were similar. although quantitative differences were found in the effects of each on different spinothalamic neurons. On the basis of these two studies, it is argued that the reticulospinal and raphe-spinal systems exert qualitatively similar effects on the responses of spinothalamic neurons evaluated in this experiment. 5. A comparison of the magnitudes of the suppression phase evoked from several different sites in the ipsilateral reticular formation and nucleus raphe magnus suggests that the descending systems arising from both these structures may be quite heterogeneous. 6. Stimulation of both regions of the brain stem produced a much greater suppression of the response of the spinothalamic neurons to slowly changing or sustained mechanical stimuli than to transient stimuli. It is suggested that the effects of descending systems arising both in the raphe nuclei and in the reticular formation on the responses of spinothalamic neurons to a mechanical stimulus are at least as dependent on the time course of the mechanical stimulus as they are on its intensity."}
{"id": "PMID:219157", "title": "Brain stem gigantocellular neurons: patterns of activity during behavior and sleep in the freely moving rat.", "content": "1. The activity of 44 single brain stem gigantocellular neurons was recorded in the freely moving rat during the following four states: quiet waking (W), waking with movement (W-M), slow-wave sleep (SWS), and rapid eye movement (REM) sleep. 2. Cells were classified into three groups on the basis of the states in which they maintained their highest rate of discharge. The three cell categories were: movement-REM (MOV-REM), movement (MOV), and quiet waking (QW) neurons. The MOV-REM neurons, comprising 68% of the cell population, discharged significantly more during waking-movement and REM sleep than during either W or SWS. The MOV neurons, 16% of the cells, showed significant increases in activity only when the rat moved. The QW neurons, also 16% of the cells, typically maintained high rates of discharge in the absence of movement. 3. The MOV-REM neurons were further divided into two subclasses of cells--phasically and tonically discharging neurons. The phasic MOV-REM cells appeared to participate in phasic motor events of REM sleep and corresponding movements during waking. The pattern of activity of the tonic MOV-REM neurons suggested that they may be involved in the generation and maintenance of the theta rhythm of the hippocampus during waking-movement and REM sleep. 4. No cells were found to discharge significantly more in REM sleep or SWS sleep than in the other states, (i.e., no REM or SWS selective cells were seen).", "contents": "Brain stem gigantocellular neurons: patterns of activity during behavior and sleep in the freely moving rat. 1. The activity of 44 single brain stem gigantocellular neurons was recorded in the freely moving rat during the following four states: quiet waking (W), waking with movement (W-M), slow-wave sleep (SWS), and rapid eye movement (REM) sleep. 2. Cells were classified into three groups on the basis of the states in which they maintained their highest rate of discharge. The three cell categories were: movement-REM (MOV-REM), movement (MOV), and quiet waking (QW) neurons. The MOV-REM neurons, comprising 68% of the cell population, discharged significantly more during waking-movement and REM sleep than during either W or SWS. The MOV neurons, 16% of the cells, showed significant increases in activity only when the rat moved. The QW neurons, also 16% of the cells, typically maintained high rates of discharge in the absence of movement. 3. The MOV-REM neurons were further divided into two subclasses of cells--phasically and tonically discharging neurons. The phasic MOV-REM cells appeared to participate in phasic motor events of REM sleep and corresponding movements during waking. The pattern of activity of the tonic MOV-REM neurons suggested that they may be involved in the generation and maintenance of the theta rhythm of the hippocampus during waking-movement and REM sleep. 4. No cells were found to discharge significantly more in REM sleep or SWS sleep than in the other states, (i.e., no REM or SWS selective cells were seen)."}
{"id": "PMID:219159", "title": "Comparison of receptive-field properties of X and Y ganglion cells with X and Y lateral geniculate cells in the cat.", "content": "1. To examine the transmission of visual information through the lateral geniculate nucleus, we have studied the receptive-field properties of 65 X and Y optic tract axons and compared them with the receptive-field properties of X and Y LGN cells in paralyzed cats anesthetized with N2O/O2 (70/30%). The same experimental conditions and quantitative methods have been used as in the preceding study of LGN cells (2). 2. The spatiotemporal organization of the receptive fields of X and Y retinal axons are similar to those of X and Y LGN cells. X ganglion cell receptive fields show a simple center-surround organization, whereas Y ganglion cell receptive fields show a more complex organization with three concentric regions: a central region of center-type response, a region of mixed center-type and surround-type responses, and a region of surround-type response. 3. The inhibitory strengh of the surrounding region was tested with a centrally located flashing light spot of successively increased diameter. As in the LGN, the inhibitory strenght of the surrounding region was stronger in retinal X-cells than in retinal Y-cells, and the strength of the inhibition decreased as the diameter of the receptive-field center increased. 4. The decrease of the inhibitory strength of the surrounding region with increasing distance from the receptive-field center was similar in the retina and in the LGN for cells belonging to the same class (X or Y) and having the same receptive-field center size. 5. The differences in properties in the LGN between small-field X-, large-field X-, and Y-cells are best explained by assuming that they are driven, respectively, by small-field X, large-field X, and Y retinal ganglion cells. There does not appear to be a significant mixing of properties either between cells having different receptive-field center sizes. 6. The principal transformation we found between retinal and LGN units is that X LGN cells have sharply lower spontaneous activities and driven activities, as compared with X ganglion cells. Y LGN units show only a small decrease in spontaneous activity in comparison with Y ganglion cells. 7. We conclude that there is a significant alteration in the LGN only in the properties of X-cells, possibly by way of a strong inhibitory pool converging on X LGN units. We further suggest that this inhibitory pool plays a role in the modulation of transmission of information through the LGN only in the X channel, while the Y channel appears to be relatively unaffected.", "contents": "Comparison of receptive-field properties of X and Y ganglion cells with X and Y lateral geniculate cells in the cat. 1. To examine the transmission of visual information through the lateral geniculate nucleus, we have studied the receptive-field properties of 65 X and Y optic tract axons and compared them with the receptive-field properties of X and Y LGN cells in paralyzed cats anesthetized with N2O/O2 (70/30%). The same experimental conditions and quantitative methods have been used as in the preceding study of LGN cells (2). 2. The spatiotemporal organization of the receptive fields of X and Y retinal axons are similar to those of X and Y LGN cells. X ganglion cell receptive fields show a simple center-surround organization, whereas Y ganglion cell receptive fields show a more complex organization with three concentric regions: a central region of center-type response, a region of mixed center-type and surround-type responses, and a region of surround-type response. 3. The inhibitory strengh of the surrounding region was tested with a centrally located flashing light spot of successively increased diameter. As in the LGN, the inhibitory strenght of the surrounding region was stronger in retinal X-cells than in retinal Y-cells, and the strength of the inhibition decreased as the diameter of the receptive-field center increased. 4. The decrease of the inhibitory strength of the surrounding region with increasing distance from the receptive-field center was similar in the retina and in the LGN for cells belonging to the same class (X or Y) and having the same receptive-field center size. 5. The differences in properties in the LGN between small-field X-, large-field X-, and Y-cells are best explained by assuming that they are driven, respectively, by small-field X, large-field X, and Y retinal ganglion cells. There does not appear to be a significant mixing of properties either between cells having different receptive-field center sizes. 6. The principal transformation we found between retinal and LGN units is that X LGN cells have sharply lower spontaneous activities and driven activities, as compared with X ganglion cells. Y LGN units show only a small decrease in spontaneous activity in comparison with Y ganglion cells. 7. We conclude that there is a significant alteration in the LGN only in the properties of X-cells, possibly by way of a strong inhibitory pool converging on X LGN units. We further suggest that this inhibitory pool plays a role in the modulation of transmission of information through the LGN only in the X channel, while the Y channel appears to be relatively unaffected."}
{"id": "PMID:219160", "title": "Electrical interaction between motoneurons and afferent terminals in cat spinal cord.", "content": "1. The electrical threshold of the terminations of single group Ia and II afferent fibers was transiently reduced by the antidromic discharge of the initial segment of spinal motoneurons in the cat. 2. This depolarization of the terminals of afferent fibers known to synapse on motoneurons confirms previous observations of antidromic electrical interaction between these structures.", "contents": "Electrical interaction between motoneurons and afferent terminals in cat spinal cord. 1. The electrical threshold of the terminations of single group Ia and II afferent fibers was transiently reduced by the antidromic discharge of the initial segment of spinal motoneurons in the cat. 2. This depolarization of the terminals of afferent fibers known to synapse on motoneurons confirms previous observations of antidromic electrical interaction between these structures."}
{"id": "PMID:219165", "title": "Emission-computed tomography and its application to imaging of acute myocardial infarction in intact dogs using Tc-99m pyrophosphate.", "content": "The techniques of emission-computed tomography have been used to obtain in vivo quantitative estimates of the three-dimensional distribution of gamma-emitting radionuclides in dog hearts. Conjugate views, obtained for 60 equiangular projections around 360 degrees by rotating the object in front of a gamma camera, were used to reconstruct multiple-level emission transaxial images for various test objects, and for dogs with surgically induced acute myocardial infarcts. Corrections for attenuation were performed in the backprojection step of the convolution algorithm used for reconstruction. Quantitative estimates of the spatial extent and concentration of activity were obtained to within 10--15% rms error. Correlations were obtained between the radionuclide and histopathologic estimates of the extent and location of infarction.", "contents": "Emission-computed tomography and its application to imaging of acute myocardial infarction in intact dogs using Tc-99m pyrophosphate. The techniques of emission-computed tomography have been used to obtain in vivo quantitative estimates of the three-dimensional distribution of gamma-emitting radionuclides in dog hearts. Conjugate views, obtained for 60 equiangular projections around 360 degrees by rotating the object in front of a gamma camera, were used to reconstruct multiple-level emission transaxial images for various test objects, and for dogs with surgically induced acute myocardial infarcts. Corrections for attenuation were performed in the backprojection step of the convolution algorithm used for reconstruction. Quantitative estimates of the spatial extent and concentration of activity were obtained to within 10--15% rms error. Correlations were obtained between the radionuclide and histopathologic estimates of the extent and location of infarction."}
{"id": "PMID:219166", "title": "Differential renal function using technetium-99m dimercaptosuccinic acid (DMSA): in vitro correlation.", "content": "The relationship between differential renal uptake of Tc-99m 2-3 dimercaptosuccinic acid (DMSA) and differential renal function was examined in normal and abnormal dogs by correlating Tc-99m DMSA localization with relative renal blood flow and creatining clearance. There was close correlation of fractional Tc-99m DMSA localization with relative renal function.", "contents": "Differential renal function using technetium-99m dimercaptosuccinic acid (DMSA): in vitro correlation. The relationship between differential renal uptake of Tc-99m 2-3 dimercaptosuccinic acid (DMSA) and differential renal function was examined in normal and abnormal dogs by correlating Tc-99m DMSA localization with relative renal blood flow and creatining clearance. There was close correlation of fractional Tc-99m DMSA localization with relative renal function."}
{"id": "PMID:219168", "title": "Radiation decomposition of technetium-99m radiopharmaceuticals.", "content": "Technetium-99m radiopharmaceuticals are shown to be subject to autoradiation-induced decomposition, which results in increasing abundance of pertechnetate in the preparation. This autodecomposition is catalyzed by the presence of oxygen, although the removal of oxygen does not prevent its occurrence. The initial appearance of pretechnetate in the radiopharmaceutical is shown to be a function of the amount of radioactivity, the quantity of stannous ion used, and the ratio of Tc-99m to total technetium in the preparation.", "contents": "Radiation decomposition of technetium-99m radiopharmaceuticals. Technetium-99m radiopharmaceuticals are shown to be subject to autoradiation-induced decomposition, which results in increasing abundance of pertechnetate in the preparation. This autodecomposition is catalyzed by the presence of oxygen, although the removal of oxygen does not prevent its occurrence. The initial appearance of pretechnetate in the radiopharmaceutical is shown to be a function of the amount of radioactivity, the quantity of stannous ion used, and the ratio of Tc-99m to total technetium in the preparation."}
{"id": "PMID:219171", "title": "Juvenile oral angiofibroma in a female.", "content": "A case of oral angiofibroma in a 14-year-old girl is presented. Unlike in earlier reports, the patient was confirmed as female by gynecological examination and other specific examinations. The possibility of the origin of the angiofibroma from the Meckel's cartilage is postulated. Any exuberant, sessile growth with a tendency toward spontaneous bleeding should be viewed with suspicion in terms of angiofibroma. Lesions such as pyogenic granulomas, hemangiomas, myxomas, and fibromyxomas should be kept in mind while making a diagnosis of angiofibroma. A biopsy examination as a routine office procedure should not be done on benign-looking masses with tendencies to bleeding.", "contents": "Juvenile oral angiofibroma in a female. A case of oral angiofibroma in a 14-year-old girl is presented. Unlike in earlier reports, the patient was confirmed as female by gynecological examination and other specific examinations. The possibility of the origin of the angiofibroma from the Meckel's cartilage is postulated. Any exuberant, sessile growth with a tendency toward spontaneous bleeding should be viewed with suspicion in terms of angiofibroma. Lesions such as pyogenic granulomas, hemangiomas, myxomas, and fibromyxomas should be kept in mind while making a diagnosis of angiofibroma. A biopsy examination as a routine office procedure should not be done on benign-looking masses with tendencies to bleeding."}
{"id": "PMID:219176", "title": "Enhancement by disulfiram (Antabuse) of toxic effects of 95 to 97% O2 on the rat lung.", "content": "Disulfiram (Antabuse), a drug used in alcohol aversion therapy, has been demonstrated to protect various species against hyperbaric O2 toxicity. In contrast, we have found that disulfiram accelerates the onset of pulmonary edema and death of rats exposed to normobaric 95 to 97% O2. When rats were given 200 mg of disulfiram per kg b.wt., 100% of the rats died at 24 to 48 hr of O2 exposure whereas only 5% of the rats died when exposed to O2 without disulfiram. This effect was not seen with an equal dose of diethyldithiocarbamate, the reduced monomer of disulfiram. The toxic effect was not due to an inhibition of superoxide dismutase, nor did disulfiram significantly affect the level of glutathione or change the reduced to oxidized glutathione ratio in the lung. Concurrent administration of 200 mg per kg b.wt. of ascorbate, vitamin E or reduced glutathione or 100 mg/kg of catalase did not affect the toxic response.", "contents": "Enhancement by disulfiram (Antabuse) of toxic effects of 95 to 97% O2 on the rat lung. Disulfiram (Antabuse), a drug used in alcohol aversion therapy, has been demonstrated to protect various species against hyperbaric O2 toxicity. In contrast, we have found that disulfiram accelerates the onset of pulmonary edema and death of rats exposed to normobaric 95 to 97% O2. When rats were given 200 mg of disulfiram per kg b.wt., 100% of the rats died at 24 to 48 hr of O2 exposure whereas only 5% of the rats died when exposed to O2 without disulfiram. This effect was not seen with an equal dose of diethyldithiocarbamate, the reduced monomer of disulfiram. The toxic effect was not due to an inhibition of superoxide dismutase, nor did disulfiram significantly affect the level of glutathione or change the reduced to oxidized glutathione ratio in the lung. Concurrent administration of 200 mg per kg b.wt. of ascorbate, vitamin E or reduced glutathione or 100 mg/kg of catalase did not affect the toxic response."}
{"id": "PMID:219178", "title": "Effect of polybrominated biphenyls on the development of hepatic excretory function.", "content": "Polybrominated biphenyls (PBBs) stimulate hepatic drug metabolism in adult and developing rats. The purpose of this investigation was to determine the influence of PBBs on the development of the liver as an organ for chemical excretion. Exposure of developing rats to polybrominated biphenyls (PBBs) by feeding 50 ppm of PBBs to pregnant or lactating mothers and rat weanlings did not produce overt toxicity when compared to controls over a 49-day postnatal period. However, prenatal and postnatal dietary exposure to PBBs resulted in elevated liver weight. In 15-day-old rats, increased liver weight after PBBs was correlated with enhanced ouabain transport from plasma into bile. Liver weight was also elevated in 21-, 35- and 49-day-old rats treated with PBBs, but this effect was not associated with stimulation of ouabain transport in these animals. Stimulation of ouabain transport after PBBs in 15-day-old rats was associated with increased hepatic uptake of ouabain. Stimulation in 15-day-old rats and not older rats may be attributed to the relative importance of uptake for ouabain transport in 15-day-old rats.", "contents": "Effect of polybrominated biphenyls on the development of hepatic excretory function. Polybrominated biphenyls (PBBs) stimulate hepatic drug metabolism in adult and developing rats. The purpose of this investigation was to determine the influence of PBBs on the development of the liver as an organ for chemical excretion. Exposure of developing rats to polybrominated biphenyls (PBBs) by feeding 50 ppm of PBBs to pregnant or lactating mothers and rat weanlings did not produce overt toxicity when compared to controls over a 49-day postnatal period. However, prenatal and postnatal dietary exposure to PBBs resulted in elevated liver weight. In 15-day-old rats, increased liver weight after PBBs was correlated with enhanced ouabain transport from plasma into bile. Liver weight was also elevated in 21-, 35- and 49-day-old rats treated with PBBs, but this effect was not associated with stimulation of ouabain transport in these animals. Stimulation of ouabain transport after PBBs in 15-day-old rats was associated with increased hepatic uptake of ouabain. Stimulation in 15-day-old rats and not older rats may be attributed to the relative importance of uptake for ouabain transport in 15-day-old rats."}
{"id": "PMID:219180", "title": "Control of phenylethanolamine N-methyltransferase by glucocorticoids in cultured bovine adrenal medullary cells.", "content": "A procedure for the disaggregation of bovine adrenal medullary cells and a system for their maintenance in primary culture is described. The effect of glucocorticoids on the epinephrine-synthesizing enzyme, phenylethanolamine N-methyltransferase (PNMT), was examined. The initial level of PNMT activity in cultured cells was maintained by cortisol for 5 days. PNMT activity in untreated cultures declined steadily. After 5 days in culture the response of PNMT activity to cortisol was lost. The EC50 for maintenance of PNMT activity was about 15 ng/ml or 4 x 10(-8) M cortisol. Steroid structural and stereochemical requirements were similar to other glucocorticoid responses. Changes in the functional group or steric configuration of position 11 of cortisol abolished activity. Progesterone inhibited the maintenance of PNMT activity by cortisol in a competitive fashion. It was concluded that the response of PNMT activity to glucocorticoids is specific and sensitive, with strict structural and stereochemical requirements.", "contents": "Control of phenylethanolamine N-methyltransferase by glucocorticoids in cultured bovine adrenal medullary cells. A procedure for the disaggregation of bovine adrenal medullary cells and a system for their maintenance in primary culture is described. The effect of glucocorticoids on the epinephrine-synthesizing enzyme, phenylethanolamine N-methyltransferase (PNMT), was examined. The initial level of PNMT activity in cultured cells was maintained by cortisol for 5 days. PNMT activity in untreated cultures declined steadily. After 5 days in culture the response of PNMT activity to cortisol was lost. The EC50 for maintenance of PNMT activity was about 15 ng/ml or 4 x 10(-8) M cortisol. Steroid structural and stereochemical requirements were similar to other glucocorticoid responses. Changes in the functional group or steric configuration of position 11 of cortisol abolished activity. Progesterone inhibited the maintenance of PNMT activity by cortisol in a competitive fashion. It was concluded that the response of PNMT activity to glucocorticoids is specific and sensitive, with strict structural and stereochemical requirements."}
{"id": "PMID:219181", "title": "Modulation of the turnover rate of hippocampal acetylcholine by neuropeptides: possible site of action of alpha-melanocyte-stimulating hormone, adrenocorticotrophic hormone and somatostatin.", "content": "The intraventricular injection of alpha-melanocyte-stimulating hormone (alpha-MSH), adrenocorticotrophic hormone (ACTH1--24) or somatostatin increases the acetylcholine turnover rate (TRACh) in the hippocampus of rats. Two to 3 weeks after surgical transection of the projections from the cingulum of the entorhinal cortex to the hippocampus the injections of these peptides can still activate hippocampal TRACh. alpha-MSH, ACTH1--24 and somatostatin also increase hippocampal TRACh when injected two to 3 hr after section of the fimbria. In contrast, the intraseptal administration of these peptides fails to change the hippocampal TRACh. The results suggest that the increase in hippocampal TRACh elicited by the three polypeptides may be caused by their interaction with receptors located in the hippocampus. Moreover, the data exclude the possibility that these peptide receptors may be located in septum or in other telencephalic areas that contain neurons projecting to the hippocampus. In addition, this study shows that the septal-hippocampal cholinergic pathway is necessary to elicit a specific stretching-yawning syndrome described by Ferrari et al. (Ann. N.Y. Acad. Sci. 104: 330--345,  1963) after injection of alpha-MSH or ACTH1--24.", "contents": "Modulation of the turnover rate of hippocampal acetylcholine by neuropeptides: possible site of action of alpha-melanocyte-stimulating hormone, adrenocorticotrophic hormone and somatostatin. The intraventricular injection of alpha-melanocyte-stimulating hormone (alpha-MSH), adrenocorticotrophic hormone (ACTH1--24) or somatostatin increases the acetylcholine turnover rate (TRACh) in the hippocampus of rats. Two to 3 weeks after surgical transection of the projections from the cingulum of the entorhinal cortex to the hippocampus the injections of these peptides can still activate hippocampal TRACh. alpha-MSH, ACTH1--24 and somatostatin also increase hippocampal TRACh when injected two to 3 hr after section of the fimbria. In contrast, the intraseptal administration of these peptides fails to change the hippocampal TRACh. The results suggest that the increase in hippocampal TRACh elicited by the three polypeptides may be caused by their interaction with receptors located in the hippocampus. Moreover, the data exclude the possibility that these peptide receptors may be located in septum or in other telencephalic areas that contain neurons projecting to the hippocampus. In addition, this study shows that the septal-hippocampal cholinergic pathway is necessary to elicit a specific stretching-yawning syndrome described by Ferrari et al. (Ann. N.Y. Acad. Sci. 104: 330--345,  1963) after injection of alpha-MSH or ACTH1--24."}
{"id": "PMID:219182", "title": "Acute renal haemodynamic and renin-angiotensin system responses to graded renal artery stenosis in the dog.", "content": "1. The acute renal haemodynamic and renin-angiotensin system responses to graded renal artery stenosis were studied in chronically instrumented, unanaesthetized dogs. 2. Stenosis was induced over 30 sec by inflation of a cuff around the renal artery to lower distal pressure to 60, 40 or 20 mmHg, with stenosis maintained for 1 hr. This resulted in an immediate fall in renal vascular resistance, but over the next 5--30 min both resistance and renal artery pressure were restored back towards prestenosis values. Only transient increases in systemic arterial blood pressure and plasma renin and angiotensin levels were seen with the two milder stenoses. Despite restoration of renal artery pressure, renal blood flow remained reduced at all grades of stenosis. 3. Pre-treatment with angiotensin I converting enzyme inhibitor or sarosine1, isoleucone8 angiotensin II greatly attenuated or abolished the restoration of renal artery pressure and renal vascular resistance after stenosis, and plasma renin and angiotensin II levels remained high. Renal dilatation was indefinitely maintained, but the normal restoration of resistance and pressure could be simulated by infusing angiotensin II into the renal artery. 4. The effective resistance to blood flow by the stenosis did not remain constant but varied with changes in the renal vascular resistance.", "contents": "Acute renal haemodynamic and renin-angiotensin system responses to graded renal artery stenosis in the dog. 1. The acute renal haemodynamic and renin-angiotensin system responses to graded renal artery stenosis were studied in chronically instrumented, unanaesthetized dogs. 2. Stenosis was induced over 30 sec by inflation of a cuff around the renal artery to lower distal pressure to 60, 40 or 20 mmHg, with stenosis maintained for 1 hr. This resulted in an immediate fall in renal vascular resistance, but over the next 5--30 min both resistance and renal artery pressure were restored back towards prestenosis values. Only transient increases in systemic arterial blood pressure and plasma renin and angiotensin levels were seen with the two milder stenoses. Despite restoration of renal artery pressure, renal blood flow remained reduced at all grades of stenosis. 3. Pre-treatment with angiotensin I converting enzyme inhibitor or sarosine1, isoleucone8 angiotensin II greatly attenuated or abolished the restoration of renal artery pressure and renal vascular resistance after stenosis, and plasma renin and angiotensin II levels remained high. Renal dilatation was indefinitely maintained, but the normal restoration of resistance and pressure could be simulated by infusing angiotensin II into the renal artery. 4. The effective resistance to blood flow by the stenosis did not remain constant but varied with changes in the renal vascular resistance."}
{"id": "PMID:219184", "title": "The effect of hypoxia on evoked potentials in the in vitro hippocampus.", "content": "1. We have studied the effect of hypoxia on transmission of electrical activity between the perforant path and the dentate granule cells in the in vitro guinea-pig hippocampus. 2. Hypoxia abolishes the evoked field potential within about 3 min, a time similar to that occurring in vivo (Andersen, 1960). 3. The evoked potential is very rapidly abolished by extracellular K+ concentrations greater than 13.4 mM; it is abolished by ouabain concentrations greater than 10(-5) M. The rate at which it is abolished increases with increasing ouabain concentrations: concentrations of about 8 x 10(-5) M abolish the evoked potential at the same rate as does hypoxia. 4. The time required to abolish the evoked potential during hypoxia decreases markedly as the extracellular K+ concentration is elevated from 4.4 to 13.4 mM. The time to abolish the potential during hypoxia is also decreased by partial replacement of the Cl- in the bathing medium by less permeant anions and by the presence of a low (10(-7) M) concentration of ouabain. All these are conditions which are expected to depolarize neuronal cell membranes. None of these alterations in the perfusing medium affect the concentrations of ATP or creatine phosphate in the hippocampal slice. Increasing extracellular Mg2+/Ca2+ to levels which reduce the evoked response by about 50% has no effect upon the time required to abolish the evoked potential during hypoxia at any concentration of extracellular [K+]. 5. These results provide evidence that the basis for the hypoxic block of the evoked potential is a depolarization of neuronal processes. They are consistent with the hypothesis that this depolarization is a result of inhibition of the Na+/K+ pump.", "contents": "The effect of hypoxia on evoked potentials in the in vitro hippocampus. 1. We have studied the effect of hypoxia on transmission of electrical activity between the perforant path and the dentate granule cells in the in vitro guinea-pig hippocampus. 2. Hypoxia abolishes the evoked field potential within about 3 min, a time similar to that occurring in vivo (Andersen, 1960). 3. The evoked potential is very rapidly abolished by extracellular K+ concentrations greater than 13.4 mM; it is abolished by ouabain concentrations greater than 10(-5) M. The rate at which it is abolished increases with increasing ouabain concentrations: concentrations of about 8 x 10(-5) M abolish the evoked potential at the same rate as does hypoxia. 4. The time required to abolish the evoked potential during hypoxia decreases markedly as the extracellular K+ concentration is elevated from 4.4 to 13.4 mM. The time to abolish the potential during hypoxia is also decreased by partial replacement of the Cl- in the bathing medium by less permeant anions and by the presence of a low (10(-7) M) concentration of ouabain. All these are conditions which are expected to depolarize neuronal cell membranes. None of these alterations in the perfusing medium affect the concentrations of ATP or creatine phosphate in the hippocampal slice. Increasing extracellular Mg2+/Ca2+ to levels which reduce the evoked response by about 50% has no effect upon the time required to abolish the evoked potential during hypoxia at any concentration of extracellular [K+]. 5. These results provide evidence that the basis for the hypoxic block of the evoked potential is a depolarization of neuronal processes. They are consistent with the hypothesis that this depolarization is a result of inhibition of the Na+/K+ pump."}
{"id": "PMID:219185", "title": "On the effect of ionophoretically applied dopamine on salivary gland cells of Nauphoeta cinerea.", "content": "1. Responses to ionophoretically applied dopamine ('ionophoretic responses') have been recorded with an intracellular micro-electrode from acini of isolated salivary glands of the cockroach, Nauphoeta cinerea. They resembled responses to nerve stimulation ('neural responses') but they usually decayed more slowly and were sometimes more rapid in onset. 2. As already described for neural resonses, ionophoretic responses (i) included a secondary phase of depolarization (although more rarely than neural responses), (ii) increased in duration with increased amplitude and (iii) when small, added superlinearly. These features therefore reflect post-synaptic processes. By contrast, tachyphylaxis was much more marked for neural responses and is therefore mainly of presynaptic origin. 3. Ionophoretic and neural responses were affected similarly by increase in temperature. The times-to-peak of both decreased with values for Q10 of about 3. 4. The differences between the onset and decay of ionophoretic and neural responses can probably be explained by the inherently different conditions of application of the agonist. The similarities therfore provide further support for dopamine as the neurotransmitter.", "contents": "On the effect of ionophoretically applied dopamine on salivary gland cells of Nauphoeta cinerea. 1. Responses to ionophoretically applied dopamine ('ionophoretic responses') have been recorded with an intracellular micro-electrode from acini of isolated salivary glands of the cockroach, Nauphoeta cinerea. They resembled responses to nerve stimulation ('neural responses') but they usually decayed more slowly and were sometimes more rapid in onset. 2. As already described for neural resonses, ionophoretic responses (i) included a secondary phase of depolarization (although more rarely than neural responses), (ii) increased in duration with increased amplitude and (iii) when small, added superlinearly. These features therefore reflect post-synaptic processes. By contrast, tachyphylaxis was much more marked for neural responses and is therefore mainly of presynaptic origin. 3. Ionophoretic and neural responses were affected similarly by increase in temperature. The times-to-peak of both decreased with values for Q10 of about 3. 4. The differences between the onset and decay of ionophoretic and neural responses can probably be explained by the inherently different conditions of application of the agonist. The similarities therfore provide further support for dopamine as the neurotransmitter."}
{"id": "PMID:219186", "title": "On the time course of the electrical response of salivary gland cells of Nauphoeta cinerea to ionophoretically applied dopamine.", "content": "1. An attempt has been made to account for the latency and slow time course of the electrical responses of salivary gland cells of Nauphoeta cinerea (Olivier) to nerve stimulation and ionophoretically applied dopamine from a pipette placed as close as possible to the acinar surface. 2. The effects have been investigated on the time course of the ionophoretic response of changes in the distance of the pipette from the acinar surface and of the amount of dopamine ejected. 3. The observed changes were smaller than those predicted by models in which the rate limiting step was assumed to be diffusion or slow receptor kinetics. Indirect evidence suggests that the time course of the response is determined by processes subsequent to receptor activation.", "contents": "On the time course of the electrical response of salivary gland cells of Nauphoeta cinerea to ionophoretically applied dopamine. 1. An attempt has been made to account for the latency and slow time course of the electrical responses of salivary gland cells of Nauphoeta cinerea (Olivier) to nerve stimulation and ionophoretically applied dopamine from a pipette placed as close as possible to the acinar surface. 2. The effects have been investigated on the time course of the ionophoretic response of changes in the distance of the pipette from the acinar surface and of the amount of dopamine ejected. 3. The observed changes were smaller than those predicted by models in which the rate limiting step was assumed to be diffusion or slow receptor kinetics. Indirect evidence suggests that the time course of the response is determined by processes subsequent to receptor activation."}
{"id": "PMID:219196", "title": "3-Substituted pyrazole derivatives as inhibitors and inactivators of liver alcohol dehydrogenase.", "content": "3-Substituted pyrazoles, HOCH2 (1), HOCH2CH2 (2), HOCH2CH2CH2 (3), ClCH2 (4), ClCH2CH2 (5), ClCH2CH2CH2 (6), and CH3CO (7), were synthesized and evaluated in vitro on horse liver alcohol dehydrogenase for their potential as inhibitors of ethanol metabolism. 1 to 6 bound to the enzyme-NAD+ complex with dissociation constants of 40 to 200 microM, much higher than the constants for the corresponding 4-substituted pyrazoles, but with the same absorption maximum at 295 nm. 4 inactivated the enzyme within a few minutes, but NAD+ protected against reaction, and 4 nonspecifically alkylated many sulfur atoms in the protein. The isomer, 4-(chloromethyl)pyrazole, behaved similarly, 5 and 6 strongly inhibited the enzyme in the presence of NAD+, due to formation of the slowly dissociable (10(-3)s-1) enzyme-NAD+-pyrazole complex, but did not irreversibly inactivate the enzyme. 7 inhibits the enzyme weakly (Kp = 5 mM). It appears that the 3-substituted pyrazoles bind to the enzyme-NAD+ complex with the reactive functional group improperly positioned for specific irreversible reaction.", "contents": "3-Substituted pyrazole derivatives as inhibitors and inactivators of liver alcohol dehydrogenase. 3-Substituted pyrazoles, HOCH2 (1), HOCH2CH2 (2), HOCH2CH2CH2 (3), ClCH2 (4), ClCH2CH2 (5), ClCH2CH2CH2 (6), and CH3CO (7), were synthesized and evaluated in vitro on horse liver alcohol dehydrogenase for their potential as inhibitors of ethanol metabolism. 1 to 6 bound to the enzyme-NAD+ complex with dissociation constants of 40 to 200 microM, much higher than the constants for the corresponding 4-substituted pyrazoles, but with the same absorption maximum at 295 nm. 4 inactivated the enzyme within a few minutes, but NAD+ protected against reaction, and 4 nonspecifically alkylated many sulfur atoms in the protein. The isomer, 4-(chloromethyl)pyrazole, behaved similarly, 5 and 6 strongly inhibited the enzyme in the presence of NAD+, due to formation of the slowly dissociable (10(-3)s-1) enzyme-NAD+-pyrazole complex, but did not irreversibly inactivate the enzyme. 7 inhibits the enzyme weakly (Kp = 5 mM). It appears that the 3-substituted pyrazoles bind to the enzyme-NAD+ complex with the reactive functional group improperly positioned for specific irreversible reaction."}
{"id": "PMID:219197", "title": "Effects of amorphous silicon dioxides on drug dissolution.", "content": "The dissolution profiles of prednisone, digoxin, and griseofulvin in simulated GI fluids were determined after solvent deposition or ball milling with three commercially available grades of amorphous silicon dioxide. The former procedure resulted in adsorbates showing evidence of drug entrapment by the two grades with larger average pore diameters. Ball milling the drugs with the grade possessing the largest average particle diameter produced triturations with the slowest dissolution rates. A relationship between drug dissolution and extent of dilution with the amorphous silicon dioxides was shown. Particle-size measurements revealed that the ball milling procedure was more apt to broaden the size distribution as compared with the solvent-deposition method of drug incorporation.", "contents": "Effects of amorphous silicon dioxides on drug dissolution. The dissolution profiles of prednisone, digoxin, and griseofulvin in simulated GI fluids were determined after solvent deposition or ball milling with three commercially available grades of amorphous silicon dioxide. The former procedure resulted in adsorbates showing evidence of drug entrapment by the two grades with larger average pore diameters. Ball milling the drugs with the grade possessing the largest average particle diameter produced triturations with the slowest dissolution rates. A relationship between drug dissolution and extent of dilution with the amorphous silicon dioxides was shown. Particle-size measurements revealed that the ball milling procedure was more apt to broaden the size distribution as compared with the solvent-deposition method of drug incorporation."}
{"id": "PMID:219198", "title": "Differential pulse polarographic determination of 2,3-dimercaptosuccinic acid and tin (II) in radiopharmaceuticals.", "content": "A differential pulse polarographic procedure was developed for the assay of dimercaptosuccinic acid and tin(II), components of a commercially available pharmaceutical kit for kidney scintigraphy. The method is quantitative and qualitative for both the chelated and unchelated forms of dimercaptosuccinic acid and tin(II) in a mixture of the two.", "contents": "Differential pulse polarographic determination of 2,3-dimercaptosuccinic acid and tin (II) in radiopharmaceuticals. A differential pulse polarographic procedure was developed for the assay of dimercaptosuccinic acid and tin(II), components of a commercially available pharmaceutical kit for kidney scintigraphy. The method is quantitative and qualitative for both the chelated and unchelated forms of dimercaptosuccinic acid and tin(II) in a mixture of the two."}
{"id": "PMID:219205", "title": "[Topographic diagnosis of lesions of the acoustico-facial nerve complex using the winking reflex].", "content": "An electrophysiological study in close to 1,500 cases of various lesions of the trigeminal nerve, the acoustico-facial complex and the brain stem was presented. It was concluded that following a detailed clinical examination which, most often, allows precise topographical diagnosis, the study of the trigemino-facial and facial reflexes appears to be an essential diagnostic tool to determine the topography of a lesion. Moreover, this method may give prognostic evaluation as well as facilitate the choice of surgical approach to the lesions of the acoustico-facial complex.", "contents": "[Topographic diagnosis of lesions of the acoustico-facial nerve complex using the winking reflex]. An electrophysiological study in close to 1,500 cases of various lesions of the trigeminal nerve, the acoustico-facial complex and the brain stem was presented. It was concluded that following a detailed clinical examination which, most often, allows precise topographical diagnosis, the study of the trigemino-facial and facial reflexes appears to be an essential diagnostic tool to determine the topography of a lesion. Moreover, this method may give prognostic evaluation as well as facilitate the choice of surgical approach to the lesions of the acoustico-facial complex."}
{"id": "PMID:219209", "title": "Characterization of an Epstein-Barr virus-induced DNA polymerase.", "content": "The addition of iododeoxyuridine to P3HR-I cell cultures led to a large increase in both Epstein-Barr virus (EBV)-induced DNA polymerase activity and early antigen-positive cells. This EBV-induced DNA polymerase was separated from the cellular alpha- and beta-polymerases by sequential column chromatography on Sepharose 6B, DEAE-cellulose, and phosphocellulose, resulting in partial purification of about 320-fold. The partially purified-EBV DNA polymerase could be distinguished from the cellular DNA polymerases by its activation by salts, its catalytic properties, and its degree of sensitivity to N-ethylmaleimide, phosphonoacetic acid, araATP, and araCTP. The viral polymerase showed properteis similar to those reported for other herpesvirus DNA polymerases. The enzyme exhibited optimal activity for copying activated calf DNA in the presence of 50 mH (NH4)2SO4 and was resistant to 150 mM (NH4)2SO4. It utilized with high efficiency template-primer poly(dC)-oligo(dG)12-18 or poly(dA)-oligo(dT)12-18, but failed to copy poly(rA)-oligo(dT)10 and oligo(dT)10, indicating that this enzyme has characters distinct from DNA polymerase gamma, reverse transcriptase, and terminal deoxynucleotidyl transferase. Phosphonacetic acid inhibited not only EBV DNA polymerase, but also, to a lesser degree, the cellular polymerase alpha. AraATP did not severely inhibit viral activity, whereas the polymerase alpha was inhibited most effectively. Both EBV polymerase and polymerase alpha were inhibited at a comparable level by araCTP.", "contents": "Characterization of an Epstein-Barr virus-induced DNA polymerase. The addition of iododeoxyuridine to P3HR-I cell cultures led to a large increase in both Epstein-Barr virus (EBV)-induced DNA polymerase activity and early antigen-positive cells. This EBV-induced DNA polymerase was separated from the cellular alpha- and beta-polymerases by sequential column chromatography on Sepharose 6B, DEAE-cellulose, and phosphocellulose, resulting in partial purification of about 320-fold. The partially purified-EBV DNA polymerase could be distinguished from the cellular DNA polymerases by its activation by salts, its catalytic properties, and its degree of sensitivity to N-ethylmaleimide, phosphonoacetic acid, araATP, and araCTP. The viral polymerase showed properteis similar to those reported for other herpesvirus DNA polymerases. The enzyme exhibited optimal activity for copying activated calf DNA in the presence of 50 mH (NH4)2SO4 and was resistant to 150 mM (NH4)2SO4. It utilized with high efficiency template-primer poly(dC)-oligo(dG)12-18 or poly(dA)-oligo(dT)12-18, but failed to copy poly(rA)-oligo(dT)10 and oligo(dT)10, indicating that this enzyme has characters distinct from DNA polymerase gamma, reverse transcriptase, and terminal deoxynucleotidyl transferase. Phosphonacetic acid inhibited not only EBV DNA polymerase, but also, to a lesser degree, the cellular polymerase alpha. AraATP did not severely inhibit viral activity, whereas the polymerase alpha was inhibited most effectively. Both EBV polymerase and polymerase alpha were inhibited at a comparable level by araCTP."}
{"id": "PMID:219210", "title": "Tryptic peptide analysis of gag gene proteins of endogenous mouse type C viruses.", "content": "Tryptic digests of the internal proteins p30, p15, p12, and p10 of mouse xenotropic, ecotropic, and amphotropic type C viruses were subjected to cation-exchange chromatography. Analysis of these maps revealed that the p30 proteins from representative isolates of all three viral subgroups were distinguishable. The p15 proteins were all unique. The p12 proteins of NZB xenotropic and wild-mouse amphotropic viruses were not identical and yielded peptide maps remarkably different from that of the ecotropic virus. The p10 proteins of xenotropic and ecotropic viruses were identical and were dissimilar to that of the wild-mouse amphotropic virus.", "contents": "Tryptic peptide analysis of gag gene proteins of endogenous mouse type C viruses. Tryptic digests of the internal proteins p30, p15, p12, and p10 of mouse xenotropic, ecotropic, and amphotropic type C viruses were subjected to cation-exchange chromatography. Analysis of these maps revealed that the p30 proteins from representative isolates of all three viral subgroups were distinguishable. The p15 proteins were all unique. The p12 proteins of NZB xenotropic and wild-mouse amphotropic viruses were not identical and yielded peptide maps remarkably different from that of the ecotropic virus. The p10 proteins of xenotropic and ecotropic viruses were identical and were dissimilar to that of the wild-mouse amphotropic virus."}
{"id": "PMID:219211", "title": "Selective inhibition of protein synthesis in virus-infected mammalian cells.", "content": "A number of translation inhibitors were tested for their effects on both control and encephalomyocarditis virus-infected mouse 3T6 cells. The virus-infected cells were specifically inhibited by gougerotin, edeine, and blasticidin S, whereas these drugs failed to penetrate into uninfected cells. Inhibition of infected cells by gougerotin became apparent when the synthesis of viral proteins commenced, suggesting that the latter process is accompanied by a permeability change in the cells that allows uptake of the drug. This permeability change was not observed in cells treated with cycloheximide soon after viral infection, although treatment with actinomycin D did not prevent inhibition of gougerotin. It is possible, therefore, that a specific viral protein is involved in the permeability change of the plasma membrane. Moreover, gougerotin was unable to inhibit protein synthesis in the presence of zinc ions, thus preventing gougerotin from entering into the infected cell. Membrane leakiness was not restricted to the encephalomyocarditis virus-3T6 system; it was also observed in mengovirus-infected 3T6 cells, Semliki Forest virus-infected BHK cells, and simian virus 40-infected CVI1 cells at the time in which the synthesis of late proteins is maximal.", "contents": "Selective inhibition of protein synthesis in virus-infected mammalian cells. A number of translation inhibitors were tested for their effects on both control and encephalomyocarditis virus-infected mouse 3T6 cells. The virus-infected cells were specifically inhibited by gougerotin, edeine, and blasticidin S, whereas these drugs failed to penetrate into uninfected cells. Inhibition of infected cells by gougerotin became apparent when the synthesis of viral proteins commenced, suggesting that the latter process is accompanied by a permeability change in the cells that allows uptake of the drug. This permeability change was not observed in cells treated with cycloheximide soon after viral infection, although treatment with actinomycin D did not prevent inhibition of gougerotin. It is possible, therefore, that a specific viral protein is involved in the permeability change of the plasma membrane. Moreover, gougerotin was unable to inhibit protein synthesis in the presence of zinc ions, thus preventing gougerotin from entering into the infected cell. Membrane leakiness was not restricted to the encephalomyocarditis virus-3T6 system; it was also observed in mengovirus-infected 3T6 cells, Semliki Forest virus-infected BHK cells, and simian virus 40-infected CVI1 cells at the time in which the synthesis of late proteins is maximal."}
{"id": "PMID:219212", "title": "Envelope proteins and replication of vesicular stomatitis virus: in vivo effects of RNA+ temperature-sensitive mutations on viral RNA synthesis.", "content": "Temperature-sensitive (ts) mutants of vesicular stomatitis virus belonging to complementation groups III and V were investigated for their in vivo RNA synthesis. The sucrose gradient patterns of the RNA species which they produced at nonpermissive temperature (39.2 degrees C) were systematically compared under different experimental conditions: variation of input multiplicity and of time of infection, superinfection with T particles, and temperature shifts. Finally, a more precise analysis of the various RNA species synthesized was carried out. It appeared that the characteristics of RNA synthesis specified at 39.2 degrees C by tsIII or tsV mutants differed from the normal RNA synthesis of vesicular stomatitis virus wild type. Their common depression at 39.2 degrees C in virion-like RNA (38S) production--i.e., so-called genome replication--was tentatively paralleled with the concomitant ts events which have been previously shown to affect the two viral envelope proteins. An overproduction of the RNA transcripts was described for mutants in group III and posed the question of a regulation process to determine the amount of RNA to be transcribed.", "contents": "Envelope proteins and replication of vesicular stomatitis virus: in vivo effects of RNA+ temperature-sensitive mutations on viral RNA synthesis. Temperature-sensitive (ts) mutants of vesicular stomatitis virus belonging to complementation groups III and V were investigated for their in vivo RNA synthesis. The sucrose gradient patterns of the RNA species which they produced at nonpermissive temperature (39.2 degrees C) were systematically compared under different experimental conditions: variation of input multiplicity and of time of infection, superinfection with T particles, and temperature shifts. Finally, a more precise analysis of the various RNA species synthesized was carried out. It appeared that the characteristics of RNA synthesis specified at 39.2 degrees C by tsIII or tsV mutants differed from the normal RNA synthesis of vesicular stomatitis virus wild type. Their common depression at 39.2 degrees C in virion-like RNA (38S) production--i.e., so-called genome replication--was tentatively paralleled with the concomitant ts events which have been previously shown to affect the two viral envelope proteins. An overproduction of the RNA transcripts was described for mutants in group III and posed the question of a regulation process to determine the amount of RNA to be transcribed."}
{"id": "PMID:219213", "title": "Role of the membrane (M) protein in endogenous inhibition of in vitro transcription by vesicular stomatitis virus.", "content": "An endogenous transcriptase inhibitor active at high concentrations of vesicular stomatitis (VS) virus was present in trypsinized whole virions but was absent from ribonucleoprotein cores containing only the L, N, and NS proteins. Poly(L-glutamic acid) effectively reversed the transcriptase inhibition. Transcription under noninhibited, inhibited, and poly(L-glutamic acid)-reversed conditions did not appear to greatly affect the nature of the RNA transcription product. The VS virion matrix (M) protein was purified to greater than 98% homogeneity and was found to have an isoelectric point of approximately 9.0. Purified M protein inhibited transcription by ribonucleoprotein cores, an effect that was partially reversed by poly(L-glutamic acid). Two group III temperature-sensitive (ts) mutants of VS virus (tsO23 and ts G31) with lesions in the M protein exhibited little or no endogenous inhibitor activity compared with two wild-type strains and a group V mutant (tsO45) with a lesion in the G protein. The data presented strongly suggest that the virion M protein is responsible for the endogenous inhibition of in vitro RNA synthesis seen at high concentrations of VS virus.", "contents": "Role of the membrane (M) protein in endogenous inhibition of in vitro transcription by vesicular stomatitis virus. An endogenous transcriptase inhibitor active at high concentrations of vesicular stomatitis (VS) virus was present in trypsinized whole virions but was absent from ribonucleoprotein cores containing only the L, N, and NS proteins. Poly(L-glutamic acid) effectively reversed the transcriptase inhibition. Transcription under noninhibited, inhibited, and poly(L-glutamic acid)-reversed conditions did not appear to greatly affect the nature of the RNA transcription product. The VS virion matrix (M) protein was purified to greater than 98% homogeneity and was found to have an isoelectric point of approximately 9.0. Purified M protein inhibited transcription by ribonucleoprotein cores, an effect that was partially reversed by poly(L-glutamic acid). Two group III temperature-sensitive (ts) mutants of VS virus (tsO23 and ts G31) with lesions in the M protein exhibited little or no endogenous inhibitor activity compared with two wild-type strains and a group V mutant (tsO45) with a lesion in the G protein. The data presented strongly suggest that the virion M protein is responsible for the endogenous inhibition of in vitro RNA synthesis seen at high concentrations of VS virus."}
{"id": "PMID:219214", "title": "Altered restriction endonuclease cleavage pattern of simian virus 40 DNA.", "content": "Three different groups of temperature-sensitive mutants of simian virus 40, isolated and characterized by Chou and Martin (J. Virol. 13:1101--1109, 1974), have been analyzed by using restriction endonucleases. Differences between the restriction endonuclease cleavage pattern of these mutants and that of the standard simian virus 40 strain have been mapped. These include the following observations: (i) tsD202 carries a defective HaeIII cleavage site at position 0.9 map units; (ii) tsB204 exhibits a defective HaIII site at position 0.21 and a defective HinIII site at 0.655 map units, and (iii) tsC219 carries a new HinIII site at position 0.15. We have isolated a few wild-type revertants from each of the temperature-sensitive mutant strains; each displays the endonuclease cleavage pattern of its parental temperature-sensitive strain.", "contents": "Altered restriction endonuclease cleavage pattern of simian virus 40 DNA. Three different groups of temperature-sensitive mutants of simian virus 40, isolated and characterized by Chou and Martin (J. Virol. 13:1101--1109, 1974), have been analyzed by using restriction endonucleases. Differences between the restriction endonuclease cleavage pattern of these mutants and that of the standard simian virus 40 strain have been mapped. These include the following observations: (i) tsD202 carries a defective HaeIII cleavage site at position 0.9 map units; (ii) tsB204 exhibits a defective HaIII site at position 0.21 and a defective HinIII site at 0.655 map units, and (iii) tsC219 carries a new HinIII site at position 0.15. We have isolated a few wild-type revertants from each of the temperature-sensitive mutant strains; each displays the endonuclease cleavage pattern of its parental temperature-sensitive strain."}
{"id": "PMID:219215", "title": "Effect of actinomycin D on the expression of herpes simplex virus-common surface antigen in cells transformed by herpes simplex virus type 2.", "content": "Using rabbit antiserum hyperimmune to herpes simplex virus (HSV) type 1, the expression of HSV-common surface antigen(s) was studied by indirect immunofluorescence tests in cells transformed by HSV type 2 and in derived tumor cells. The following results were obtained. (i) Antiserum to HSV type 1 reacted specifically with surface antigen present on the plasma membrane of both HSV type 2-infected and HSV type 2-transformed hamster cells. (ii) The expression of this antigen was enhanced in the absence of active protein synthesis in transformed cells, but not in tumor cells, after culture for 3 to 5 h at 37 degrees C. (iii) This enhancement of expression was maintained for 20 h in the presence of actinomycin D, but this prolonged expression required active protein synthesis. (iv) The enhancing effect observed in the presence of actinomycin D continued for some time after removal of the drug, for example, for 20 h after 5 h of treatment with 2 microgram/ml of actinomycin D per ml. Actinomycin D had no detectable effect on antigen expression in tumor cells. (v) The protease inhibitor antipain inhibited the actinomycin D-enhanced expression without causing significant cell damage but did not modify the transient enhanced expression of antigen when cells were seeded in the absence of actinomycin D. These results indicate that in transformed cells antigen expression can be enhanced in at least two ways.", "contents": "Effect of actinomycin D on the expression of herpes simplex virus-common surface antigen in cells transformed by herpes simplex virus type 2. Using rabbit antiserum hyperimmune to herpes simplex virus (HSV) type 1, the expression of HSV-common surface antigen(s) was studied by indirect immunofluorescence tests in cells transformed by HSV type 2 and in derived tumor cells. The following results were obtained. (i) Antiserum to HSV type 1 reacted specifically with surface antigen present on the plasma membrane of both HSV type 2-infected and HSV type 2-transformed hamster cells. (ii) The expression of this antigen was enhanced in the absence of active protein synthesis in transformed cells, but not in tumor cells, after culture for 3 to 5 h at 37 degrees C. (iii) This enhancement of expression was maintained for 20 h in the presence of actinomycin D, but this prolonged expression required active protein synthesis. (iv) The enhancing effect observed in the presence of actinomycin D continued for some time after removal of the drug, for example, for 20 h after 5 h of treatment with 2 microgram/ml of actinomycin D per ml. Actinomycin D had no detectable effect on antigen expression in tumor cells. (v) The protease inhibitor antipain inhibited the actinomycin D-enhanced expression without causing significant cell damage but did not modify the transient enhanced expression of antigen when cells were seeded in the absence of actinomycin D. These results indicate that in transformed cells antigen expression can be enhanced in at least two ways."}
{"id": "PMID:219216", "title": "Analysis of integrated avian RNA tumor virus DNA in transformed chicken, duck and quail fibroblasts.", "content": "The state of integration of avian sarcoma virus DNA in the genomes of transformed chicken, duck, and quail fibroblasts was deduced by means of restriction enzyme digestion of total cell DNA, gel electrophoresis, and subsequent analysis by the procedure of Southern. The cells used in these studies were either mass-infected cultures or clones of infected cells selected by their ability to form colonies in agar. For both mass-infected cultures and clones of cells of all three species, we found that integration occurred at a specific site on the viral genome but appeared to occur at many sites on the cell genome. At least some of the integrated viral DNA existed as intact nonpermuted species flanked by direct terminal repeats of at least 0.134 megadalton (217 base pairs). For each of 12 transformed quail clones studied, it was possible to detect, after digestion with Kpn I, unique junctions between viral and cellular DNA. That is, at our level of analysis, the integration site on the cell genome for each clone was different. However, within each of the 17 chicken and 9 duck clones of transformed cells, a heterogeneity presumably occurred during the outgrowth of the cell clone population, in that we could not readily detect identifiable cell-virus junction fragments.", "contents": "Analysis of integrated avian RNA tumor virus DNA in transformed chicken, duck and quail fibroblasts. The state of integration of avian sarcoma virus DNA in the genomes of transformed chicken, duck, and quail fibroblasts was deduced by means of restriction enzyme digestion of total cell DNA, gel electrophoresis, and subsequent analysis by the procedure of Southern. The cells used in these studies were either mass-infected cultures or clones of infected cells selected by their ability to form colonies in agar. For both mass-infected cultures and clones of cells of all three species, we found that integration occurred at a specific site on the viral genome but appeared to occur at many sites on the cell genome. At least some of the integrated viral DNA existed as intact nonpermuted species flanked by direct terminal repeats of at least 0.134 megadalton (217 base pairs). For each of 12 transformed quail clones studied, it was possible to detect, after digestion with Kpn I, unique junctions between viral and cellular DNA. That is, at our level of analysis, the integration site on the cell genome for each clone was different. However, within each of the 17 chicken and 9 duck clones of transformed cells, a heterogeneity presumably occurred during the outgrowth of the cell clone population, in that we could not readily detect identifiable cell-virus junction fragments."}
{"id": "PMID:219217", "title": "Morphological and biochemical characterization of viral particles produced by the tsO45 mutant of vesicular stomatitis virus at restrictive temperature.", "content": "The growth at restrictive temperature of tsO45, a group V (glycoprotein) conditional lethal mutant of vesicular stomatitis virus (VSV), was demonstrated to result in the production of large numbers of noninfectious viral particles. The infectivity of these tsO45 particles could be enhanced by procedures known to promote membrane fusion. Morphologically and biochemically these particles differed from wild-type VSV by their lack of viral glycoprotein. The other structural proteins of VSV were present and indistinguishable by size and relative proportion from those of virus grown at the permissive temperature. Examination of glycoprotein maturation at the restrictive temperature (39.5 degrees C) in tsO45-infected cells demonstrated the synthesis of normal viral glycoprotein but failed to demonstrate the presence of this glycoprotein in either the cell membrane or the envelope of free virions. The further absence of soluble viral glycoprotein from the supernatants of such cells strongly suggests that viral glycoprotein may not be necessary for the successful budding of VSV.", "contents": "Morphological and biochemical characterization of viral particles produced by the tsO45 mutant of vesicular stomatitis virus at restrictive temperature. The growth at restrictive temperature of tsO45, a group V (glycoprotein) conditional lethal mutant of vesicular stomatitis virus (VSV), was demonstrated to result in the production of large numbers of noninfectious viral particles. The infectivity of these tsO45 particles could be enhanced by procedures known to promote membrane fusion. Morphologically and biochemically these particles differed from wild-type VSV by their lack of viral glycoprotein. The other structural proteins of VSV were present and indistinguishable by size and relative proportion from those of virus grown at the permissive temperature. Examination of glycoprotein maturation at the restrictive temperature (39.5 degrees C) in tsO45-infected cells demonstrated the synthesis of normal viral glycoprotein but failed to demonstrate the presence of this glycoprotein in either the cell membrane or the envelope of free virions. The further absence of soluble viral glycoprotein from the supernatants of such cells strongly suggests that viral glycoprotein may not be necessary for the successful budding of VSV."}
{"id": "PMID:219218", "title": "Mutational alterations within the simian virus 40 leader segment generate altered 16S and 19S mRNA's.", "content": "We have analyzed the structure of the late cytoplasmic RNAs made after infection with wild-type simian virus 40 and a set of viable mutants, four of which have deletions and one an insertion within the nucleotide sequence specifying the leader segment of the 16S and 19S mRNA's. The principal findings are: (i) simian virus 40 16S and 19S mRNA's made during infections with wild-type virnds and possibly in the nucleotide sequence comprising the \"leader\" segments. (II) \"Spliced\" 16S and 19S mRNA's are made during infections with each of the mutants although, in some cases, the ratio of 19S to 16S mRNA species is reduced. (iii) The deletion or insertion of nucleotides within the DNA segment defined by map position 0.70 to 0.75 causes striking alterations in the types of leader structures in the late mRNAs. (iv) Many of the late RNA leader segments produced after infection with the mutants appear to be multiply spliced, i.e., instead of the major 200- to 205-nucleotide-long leader segment present in wild-type 16S mRNA, the RNAs produced by several of the deletion mutants have leaders with whort discontiguous segments.", "contents": "Mutational alterations within the simian virus 40 leader segment generate altered 16S and 19S mRNA's. We have analyzed the structure of the late cytoplasmic RNAs made after infection with wild-type simian virus 40 and a set of viable mutants, four of which have deletions and one an insertion within the nucleotide sequence specifying the leader segment of the 16S and 19S mRNA's. The principal findings are: (i) simian virus 40 16S and 19S mRNA's made during infections with wild-type virnds and possibly in the nucleotide sequence comprising the \"leader\" segments. (II) \"Spliced\" 16S and 19S mRNA's are made during infections with each of the mutants although, in some cases, the ratio of 19S to 16S mRNA species is reduced. (iii) The deletion or insertion of nucleotides within the DNA segment defined by map position 0.70 to 0.75 causes striking alterations in the types of leader structures in the late mRNAs. (iv) Many of the late RNA leader segments produced after infection with the mutants appear to be multiply spliced, i.e., instead of the major 200- to 205-nucleotide-long leader segment present in wild-type 16S mRNA, the RNAs produced by several of the deletion mutants have leaders with whort discontiguous segments."}
{"id": "PMID:219219", "title": "Association of simian virus 40 T antigen with simian virus 40 nucleoprotein complexes.", "content": "Viral nucleoprotein complexes were extracted from the nuclei of simian virus 40 (SV40)-infected TC7 cells by low-salt treatment in the absence of detergent, followed by sedimentation on neutral sucrose gradients. Two forms of SV40 nucleoprotein complexes, those containing SV40 replicative intermediate DNA and those containing SV40 (I) DNA, were separated from one another and were found to have sedimentation values of 125 and 93S, respectively. [(35)S]methioninelabeled proteins in the nucleoprotein complexes were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In addition to VP1, VP3, and histones, a protein with a molecular weight of 100,000 (100K) is present in the nucleoprotein complexes containing SV40 (I) DNA. The 100K protein was confirmed as SV40 100K T antigen, both by immunoprecipitation with SV40 anti-T serum and by tryptic peptide mapping. The 100K T antigen is predominantly associated with the SV40 (I) DNA-containing complexes. The 17K T antigen, however, is not associated with the SV40 (I) DNA-containing nucleoprotein complexes. The functional significance of the SV40 100K T antigen in the SV40 (I) DNA-containing nucleoprotein complexes was examined by immunoprecipitation of complexes from tsA58-infected TC7 cells. The 100K T antigen is present in nucleoprotein complexes extracted from cells grown at the permissive temperature but is clearly absent from complexes extracted from cells grown at the permissive temperature and shifted up to the nonpermissive temperature for 1 h before extraction, suggesting that the association of the 100K T antigen with the SV40 nucleoprotein complexes is involved in the initiation of SV40 DNA synthesis.", "contents": "Association of simian virus 40 T antigen with simian virus 40 nucleoprotein complexes. Viral nucleoprotein complexes were extracted from the nuclei of simian virus 40 (SV40)-infected TC7 cells by low-salt treatment in the absence of detergent, followed by sedimentation on neutral sucrose gradients. Two forms of SV40 nucleoprotein complexes, those containing SV40 replicative intermediate DNA and those containing SV40 (I) DNA, were separated from one another and were found to have sedimentation values of 125 and 93S, respectively. [(35)S]methioninelabeled proteins in the nucleoprotein complexes were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In addition to VP1, VP3, and histones, a protein with a molecular weight of 100,000 (100K) is present in the nucleoprotein complexes containing SV40 (I) DNA. The 100K protein was confirmed as SV40 100K T antigen, both by immunoprecipitation with SV40 anti-T serum and by tryptic peptide mapping. The 100K T antigen is predominantly associated with the SV40 (I) DNA-containing complexes. The 17K T antigen, however, is not associated with the SV40 (I) DNA-containing nucleoprotein complexes. The functional significance of the SV40 100K T antigen in the SV40 (I) DNA-containing nucleoprotein complexes was examined by immunoprecipitation of complexes from tsA58-infected TC7 cells. The 100K T antigen is present in nucleoprotein complexes extracted from cells grown at the permissive temperature but is clearly absent from complexes extracted from cells grown at the permissive temperature and shifted up to the nonpermissive temperature for 1 h before extraction, suggesting that the association of the 100K T antigen with the SV40 nucleoprotein complexes is involved in the initiation of SV40 DNA synthesis."}
{"id": "PMID:219220", "title": "Adenovirus type 12 gene 401 function and maintenance of transformation.", "content": "Rat (3Y1) and hamster embryo brain cells were transformed by wild-type adenovirus type 12 or the DNA-minus temperature-sensitive mutant ts401. The ts401-transformed 3Y1 cells, but not the wild-type transformants, displayed a temperature-sensitive response with respect to the following characteristics of the transformed phenotype: morphology, saturation density, growth rate, cloning in soft agar, colony formation on plastic at low cell densities in 1% serum medium, and the T antigen(s). Temperature shift-down experiments showed that the density-dependent inhibition of growth of the ts401-transformed cells was reversible, as was, to some extent, the low efficiency of colony formation at low cell densities in 1% serum. Examination of hamster transformants for their ability to clone in soft agar at permissive and nonpermissive temperatures showed that this property was temperature dependent, again only in the ts401 transformants and not in the wild-type transformants. Alteration in uptake of 2-deoxyglucose or in intracellular cyclic AMP content was not a characteristic of the adenovirus-transformed phenotype in the 3Y1 cells. The findings suggest that an active 401 function is required for maintenance of the adenovirus-transformed cell pheno-type.", "contents": "Adenovirus type 12 gene 401 function and maintenance of transformation. Rat (3Y1) and hamster embryo brain cells were transformed by wild-type adenovirus type 12 or the DNA-minus temperature-sensitive mutant ts401. The ts401-transformed 3Y1 cells, but not the wild-type transformants, displayed a temperature-sensitive response with respect to the following characteristics of the transformed phenotype: morphology, saturation density, growth rate, cloning in soft agar, colony formation on plastic at low cell densities in 1% serum medium, and the T antigen(s). Temperature shift-down experiments showed that the density-dependent inhibition of growth of the ts401-transformed cells was reversible, as was, to some extent, the low efficiency of colony formation at low cell densities in 1% serum. Examination of hamster transformants for their ability to clone in soft agar at permissive and nonpermissive temperatures showed that this property was temperature dependent, again only in the ts401 transformants and not in the wild-type transformants. Alteration in uptake of 2-deoxyglucose or in intracellular cyclic AMP content was not a characteristic of the adenovirus-transformed phenotype in the 3Y1 cells. The findings suggest that an active 401 function is required for maintenance of the adenovirus-transformed cell pheno-type."}
{"id": "PMID:219221", "title": "Epstein-Barr virus-specific RNA. III. Mapping of DNA encoding viral RNA in restringent infection.", "content": "Namalwa and Raji cells, originally obtained from a Burkitt tumor biopsy, grow as continuous cell lines in vitro and contain the Epstein-Barr virus (EBV)-related nuclear antigen EBNA (B. M. Reedman and G. Klein, Int. J. Cancer 11:499-520, 1973) and RNA homologous to at least 17 and 30% of the EBV genome, respectively (S. D. Hayward and E. Kieff, J. Virol. 18:518-525, 1976; T. Orellana and E. Kieff, J. Virol. 22:321-330, 1977). The polyribosomal and polyadenylated [poly(A)+] RNA fractions of Namalwa and Raji cells are enriched for a class of viral RNA homologous to 5 to 7% of EBV DNA (Hayward and Kieff, J. Virol. 18:518-525, 1976; Orellana and Kieff, J. Virol. 22:321-330, 1977). The objective of the experiments described in this communication was to determine the location within the map of the EBV genome (D. Given and E. Kieff, J. Virol. 28:524-542, 1978) of the DNA which encodes the viral RNA in the poly(A)+ and non-polyadenylated [poly(A)-] RNA fractions of Namalwa cells. Hybridization of labeled DNA homologous to Namalwa poly(A)+ or poly(A)- RNA to blots containing EcoRI, Hsu I, or Hsu I/EcoRI double-cut fragments of EBV (B95-8) or (W91) DNA indicated that these RNAs are encoded by DNA contained primarily in the Hsu I A/EcoRI A and Hsu I B/EcoRI A fragments and, to a lesser extent, in other fragments of the EBV genome. Hybridizations of Namalwa poly(A)+ and poly(A)- RNA in solution to denatured labeled EcoRI A or B fragments, Hsu I A, B, or D fragments, and Hsu I A/EcoRI A or Bam I S fragments and of Raji polyribosomal poly(A)+ RNA to the EcoRI A fragment indicated that (i) Namalwa poly(A)+ RNA is encoded primarily by 6 x 10(5) daltons of a 2 x 10(6)-dalton segment of DNA, Bam I S, which is tandemly reiterated, approximately 10 times, in the Hsu I A/EcoRI A fragment and is encoded to a lesser extent by DNA in the Hsu I B, EcoRI B, and Hsu I D fragments. Raji polyribosomal poly(A)+ RNA is encoded by a similar fraction of the EcoRI A fragment as that which encodes Namalwa poly(A)+ RNA. (ii) The fraction of the Bam I S fragment homologous to Namalwa poly(A)- RNA is similar to the fraction homologous to Namalwa poly(A)+ RNA. However, Namalwa poly(A)- RNA is homologous to a larger fraction of the DNA in the Hsu I B, Hsu I D, and EcoRI B fragments.", "contents": "Epstein-Barr virus-specific RNA. III. Mapping of DNA encoding viral RNA in restringent infection. Namalwa and Raji cells, originally obtained from a Burkitt tumor biopsy, grow as continuous cell lines in vitro and contain the Epstein-Barr virus (EBV)-related nuclear antigen EBNA (B. M. Reedman and G. Klein, Int. J. Cancer 11:499-520, 1973) and RNA homologous to at least 17 and 30% of the EBV genome, respectively (S. D. Hayward and E. Kieff, J. Virol. 18:518-525, 1976; T. Orellana and E. Kieff, J. Virol. 22:321-330, 1977). The polyribosomal and polyadenylated [poly(A)+] RNA fractions of Namalwa and Raji cells are enriched for a class of viral RNA homologous to 5 to 7% of EBV DNA (Hayward and Kieff, J. Virol. 18:518-525, 1976; Orellana and Kieff, J. Virol. 22:321-330, 1977). The objective of the experiments described in this communication was to determine the location within the map of the EBV genome (D. Given and E. Kieff, J. Virol. 28:524-542, 1978) of the DNA which encodes the viral RNA in the poly(A)+ and non-polyadenylated [poly(A)-] RNA fractions of Namalwa cells. Hybridization of labeled DNA homologous to Namalwa poly(A)+ or poly(A)- RNA to blots containing EcoRI, Hsu I, or Hsu I/EcoRI double-cut fragments of EBV (B95-8) or (W91) DNA indicated that these RNAs are encoded by DNA contained primarily in the Hsu I A/EcoRI A and Hsu I B/EcoRI A fragments and, to a lesser extent, in other fragments of the EBV genome. Hybridizations of Namalwa poly(A)+ and poly(A)- RNA in solution to denatured labeled EcoRI A or B fragments, Hsu I A, B, or D fragments, and Hsu I A/EcoRI A or Bam I S fragments and of Raji polyribosomal poly(A)+ RNA to the EcoRI A fragment indicated that (i) Namalwa poly(A)+ RNA is encoded primarily by 6 x 10(5) daltons of a 2 x 10(6)-dalton segment of DNA, Bam I S, which is tandemly reiterated, approximately 10 times, in the Hsu I A/EcoRI A fragment and is encoded to a lesser extent by DNA in the Hsu I B, EcoRI B, and Hsu I D fragments. Raji polyribosomal poly(A)+ RNA is encoded by a similar fraction of the EcoRI A fragment as that which encodes Namalwa poly(A)+ RNA. (ii) The fraction of the Bam I S fragment homologous to Namalwa poly(A)- RNA is similar to the fraction homologous to Namalwa poly(A)+ RNA. However, Namalwa poly(A)- RNA is homologous to a larger fraction of the DNA in the Hsu I B, Hsu I D, and EcoRI B fragments."}
{"id": "PMID:219222", "title": "Control of herpes simplex virus type 1 mRNA synthesis in cells infected with wild-type virus or the temperature-sensitive mutant tsK.", "content": "This paper deals with control of mRNA levels, assayed by in vitro translation, in cells infected with herpes simplex virus type 1 (HSV-1). A particularly useful marker has been pyrimidine deoxyribonucleoside kinase (dPyK) mRNA, for which the enzymatically active product can be assayed quantitatively. Cells infected with the HSV-1 temperature-sensitive mutant tsK at the nonpermissive temperature (38.5 degrees C) or with wild-type HSV-1 in the continuous presence of cycloheximide contained no detectable dPyK mRNA. Upon temperature shift-down of tsK-infected cells to 31 degrees C, dPyK mRNA was produced, and this event was inhibited by actinomycin D but not cycloheximide. This result demonstrated that the defective polypeptide in tsK-infected cells was involved in transcription of the dPyK gene and could regain activity at 31 degrees C. Because tsK-infected cells synthesized mainly immediate early polypeptides at 38.5 degrees C, the involvement of this polypeptide class in synthesis of dPyK mRNA was investigated. Analysis of the kinetics of inductions of dPyK mRNA indicated that the temperature-sensitive lesion in tsK lies in an immediate early polypeptide which is directly responsible for activation of the dPyK gene at the transcriptional level.", "contents": "Control of herpes simplex virus type 1 mRNA synthesis in cells infected with wild-type virus or the temperature-sensitive mutant tsK. This paper deals with control of mRNA levels, assayed by in vitro translation, in cells infected with herpes simplex virus type 1 (HSV-1). A particularly useful marker has been pyrimidine deoxyribonucleoside kinase (dPyK) mRNA, for which the enzymatically active product can be assayed quantitatively. Cells infected with the HSV-1 temperature-sensitive mutant tsK at the nonpermissive temperature (38.5 degrees C) or with wild-type HSV-1 in the continuous presence of cycloheximide contained no detectable dPyK mRNA. Upon temperature shift-down of tsK-infected cells to 31 degrees C, dPyK mRNA was produced, and this event was inhibited by actinomycin D but not cycloheximide. This result demonstrated that the defective polypeptide in tsK-infected cells was involved in transcription of the dPyK gene and could regain activity at 31 degrees C. Because tsK-infected cells synthesized mainly immediate early polypeptides at 38.5 degrees C, the involvement of this polypeptide class in synthesis of dPyK mRNA was investigated. Analysis of the kinetics of inductions of dPyK mRNA indicated that the temperature-sensitive lesion in tsK lies in an immediate early polypeptide which is directly responsible for activation of the dPyK gene at the transcriptional level."}
{"id": "PMID:219223", "title": "Extracellular cleavage of the glycoprotein precursor of Rous sarcoma virus.", "content": "The kinetics of cleavage of pr92gp, the precursor of the two glycoproteins of Rous sarcoma virus gp85 and gp35, were followed. Viral glycoproteins were detected by immunoprecipitation with anti-gp85 and anti-gp35 serum. It could be shown in pulse-chase experiments that little or no intracellular cleavage of the precursor took place during the time in which the majority of newly synthesized viral glycoprotein was exported from the cells. Soon after its synthesis, however, pr92gp underwent some modification that made it migrate slightly faster on sodium dodecyl sulfate-polyacrylamide gels. Under steady state conditions the precursor was shown to be the predominant form of intracellular viral glycoprotein. Virus which was harvested every 2 min from infected cells prelabeled for 90 min with [3H]mannose contained mostly uncleaved and only a little mature glycoprotein. By incubation of this freshly released virus in serum-free buffer, the majority of the glycoprotein precursor could be cleaved into mature gp85 and gp35. Virus harvested every 10 min contained only mature glycoproteins.", "contents": "Extracellular cleavage of the glycoprotein precursor of Rous sarcoma virus. The kinetics of cleavage of pr92gp, the precursor of the two glycoproteins of Rous sarcoma virus gp85 and gp35, were followed. Viral glycoproteins were detected by immunoprecipitation with anti-gp85 and anti-gp35 serum. It could be shown in pulse-chase experiments that little or no intracellular cleavage of the precursor took place during the time in which the majority of newly synthesized viral glycoprotein was exported from the cells. Soon after its synthesis, however, pr92gp underwent some modification that made it migrate slightly faster on sodium dodecyl sulfate-polyacrylamide gels. Under steady state conditions the precursor was shown to be the predominant form of intracellular viral glycoprotein. Virus which was harvested every 2 min from infected cells prelabeled for 90 min with [3H]mannose contained mostly uncleaved and only a little mature glycoprotein. By incubation of this freshly released virus in serum-free buffer, the majority of the glycoprotein precursor could be cleaved into mature gp85 and gp35. Virus harvested every 10 min contained only mature glycoproteins."}
{"id": "PMID:219224", "title": "Specific protein phosphorylation in interferon-treated uninfected and virus-infected mouse L929 cells: enhancement by double-stranded RNA.", "content": "The enhanced phosphorylation of specific protein(s) observed in extracts from interferon-treated cells (in the presence of ATP and double-stranded [ds] RNA) was also seen in intact mouse L929 cells upon treatment with dsRNA, polyriboinosinic.polyribocytidylic acid [poly(rI.rC)] or reovirus dsRNA, using 32Pi as radiolabel. Labeling of a 65,000-dalton protein(s) with 32P was greatly increased in interferon-treated cells in the presence of added dsRNA, suggesting that the expression in vivo of the kinase activity involved is regulated by dsRNA. This was used as a test system to investigate whether the activity of interferon-induced enzyme(s) is stimulated following virus infection, possibly owing to the accumulation of dsRNA. No obvious increase in 32P-labeling of 65,000-dalton protein(s) was observed upon infection of interferon-treated cells with mengovirus or vesicular stomatitis virus. A basal level of 32P-labeling of the 65,000-dalton protein(s) was detected in interferon-treated cells in the absence of added dsRNA, indicating a basal level of expression of the kinase activity involved. The possible implications of these results are discussed.", "contents": "Specific protein phosphorylation in interferon-treated uninfected and virus-infected mouse L929 cells: enhancement by double-stranded RNA. The enhanced phosphorylation of specific protein(s) observed in extracts from interferon-treated cells (in the presence of ATP and double-stranded [ds] RNA) was also seen in intact mouse L929 cells upon treatment with dsRNA, polyriboinosinic.polyribocytidylic acid [poly(rI.rC)] or reovirus dsRNA, using 32Pi as radiolabel. Labeling of a 65,000-dalton protein(s) with 32P was greatly increased in interferon-treated cells in the presence of added dsRNA, suggesting that the expression in vivo of the kinase activity involved is regulated by dsRNA. This was used as a test system to investigate whether the activity of interferon-induced enzyme(s) is stimulated following virus infection, possibly owing to the accumulation of dsRNA. No obvious increase in 32P-labeling of 65,000-dalton protein(s) was observed upon infection of interferon-treated cells with mengovirus or vesicular stomatitis virus. A basal level of 32P-labeling of the 65,000-dalton protein(s) was detected in interferon-treated cells in the absence of added dsRNA, indicating a basal level of expression of the kinase activity involved. The possible implications of these results are discussed."}
{"id": "PMID:219225", "title": "Growth and maturation of a vesicular stomatitis virus temperature-sensitive mutant and its central nervous system isolate.", "content": "A temperature-sensitive (ts) mutant of vesicular stomatitis virus (VSV), tsG31, produces a prolonged central nervous system disease in mice with pathological features similar to those of slow viral diseases. tsG31 and the subsequent virus recovered from the central nervous system (tsG31BP) of mice infected with tsG31 were compared with the parental wild-type (WT) VSV for plaque morphology, growth kinetics, thermal sensitivity of the virions, and viral protein synthesis and maturation. Several properties of the central nervous system isolate distinguished this virus from the original tsG31 and the WT VSV. The WT VSV produced clear plaques with complete cell lysis, and the tsG31 produced diffuse plaques and incomplete cell lysis, whereas the tsG31BP had clear plaques similar to those of the WT VSV. Although plaque morphology suggested that tsG31BP virus was a revertant to the WT, growth kinetics in either BHK-21 or neuroblastoma (N-18) cells indicated that this virus was similar to tsG31, with a productive cycle at 31 degrees C and no infectious virus at 39 degrees C. At 37 degrees C, however, the tsG31BP matured much slower than did the original tsG31 (and produced only 1% of the yield measured at 31 degrees C). WT VSV produced similar quantities of infectious virions at 31, 37, and 39 degrees C. The lack of infectious virions at 39 degrees C for the ts mutants was presumably not due to a greater rate of inactivation at 39 degrees C. Unlike WT VSV, which synthesized viral proteins equally well at all three temperatures, tsG31 had a reduced synthesis of all the structural proteins at 37 and 39 degrees C, compared with that at 31 degrees C; the formation of the M protein was most temperature sensitive. In addition, fractionation of the infected cells indicated that the incorporation of the M and N proteins into the cellular membranes was also disrupted at the higher, nonpermissive temperatures. Several characteristics of protein synthesis during tsG31BP infection at 39 degrees C distinguished this virus from tsG31: (i) no mature viral proteins were detected at 39 degrees C; (ii) several host proteins were [ill], suggesting that the virus was incapable of completely depressing host macromolecular synthesis; and (iii) a great proportion of the incorporated radioactivity was found in unusually high-molecular-weight proteins. In addition, at 37 degrees C, the tsG31BP virus showed a decreased synthesis of viral proteins and reduced assembly of the viral structural proteins.", "contents": "Growth and maturation of a vesicular stomatitis virus temperature-sensitive mutant and its central nervous system isolate. A temperature-sensitive (ts) mutant of vesicular stomatitis virus (VSV), tsG31, produces a prolonged central nervous system disease in mice with pathological features similar to those of slow viral diseases. tsG31 and the subsequent virus recovered from the central nervous system (tsG31BP) of mice infected with tsG31 were compared with the parental wild-type (WT) VSV for plaque morphology, growth kinetics, thermal sensitivity of the virions, and viral protein synthesis and maturation. Several properties of the central nervous system isolate distinguished this virus from the original tsG31 and the WT VSV. The WT VSV produced clear plaques with complete cell lysis, and the tsG31 produced diffuse plaques and incomplete cell lysis, whereas the tsG31BP had clear plaques similar to those of the WT VSV. Although plaque morphology suggested that tsG31BP virus was a revertant to the WT, growth kinetics in either BHK-21 or neuroblastoma (N-18) cells indicated that this virus was similar to tsG31, with a productive cycle at 31 degrees C and no infectious virus at 39 degrees C. At 37 degrees C, however, the tsG31BP matured much slower than did the original tsG31 (and produced only 1% of the yield measured at 31 degrees C). WT VSV produced similar quantities of infectious virions at 31, 37, and 39 degrees C. The lack of infectious virions at 39 degrees C for the ts mutants was presumably not due to a greater rate of inactivation at 39 degrees C. Unlike WT VSV, which synthesized viral proteins equally well at all three temperatures, tsG31 had a reduced synthesis of all the structural proteins at 37 and 39 degrees C, compared with that at 31 degrees C; the formation of the M protein was most temperature sensitive. In addition, fractionation of the infected cells indicated that the incorporation of the M and N proteins into the cellular membranes was also disrupted at the higher, nonpermissive temperatures. Several characteristics of protein synthesis during tsG31BP infection at 39 degrees C distinguished this virus from tsG31: (i) no mature viral proteins were detected at 39 degrees C; (ii) several host proteins were [ill], suggesting that the virus was incapable of completely depressing host macromolecular synthesis; and (iii) a great proportion of the incorporated radioactivity was found in unusually high-molecular-weight proteins. In addition, at 37 degrees C, the tsG31BP virus showed a decreased synthesis of viral proteins and reduced assembly of the viral structural proteins."}
{"id": "PMID:219226", "title": "Gene D5 product of bacteriophage T5: DNA-binding protein affecting DNA replication and late gene expression.", "content": "Gene D5 is not only necessary for replication of bacteriophage T5 DNA and for shutoff of expression of some early genes, but has been found to be necessary also for the expression of late T5 genes. The polypeptide product of gene D5 has been identified, an intragenic map of gene D5 has been constructed, and the direction of transcription of gene D5 has been established. The polypeptide coded by gene D5 has been shown to be a DNA-binding protein with affinity for both double- and single-stranded DNA.", "contents": "Gene D5 product of bacteriophage T5: DNA-binding protein affecting DNA replication and late gene expression. Gene D5 is not only necessary for replication of bacteriophage T5 DNA and for shutoff of expression of some early genes, but has been found to be necessary also for the expression of late T5 genes. The polypeptide product of gene D5 has been identified, an intragenic map of gene D5 has been constructed, and the direction of transcription of gene D5 has been established. The polypeptide coded by gene D5 has been shown to be a DNA-binding protein with affinity for both double- and single-stranded DNA."}
{"id": "PMID:219227", "title": "Selective packaging of host tRNA's by murine leukemia virus particles does not require genomic RNA.", "content": "The 4S RNA contained in RNA tumor virus particles consists of a selected population of host tRNA's. However, the mechanism by which virions select host tRNA's has not been elucidated. We have considered a model which specifies that 35S genomic RNA determines which tRNA's are to be encapsidated as well as the relative amounts of these tRNA's within the virion. The model was tested by comparing the free 4S RNA composition of normal murine leukemia virus (MuLV) particles and noninfectious virions from actinomycin D (ActD)-treated cells, which are deficient in genomic RNA (ActD virions). Viral 4S RNA was analyzed by two-dimensional polyacrylamide gel electrophoresis. Surprisingly, the patterns obtained for control and ActD 4S RNA were identical to each other and were clearly distinct from the cell 4S RNA pattern. The viral patterns had three prominent areas of radioactivity. One of the spots was identified on the basis of its oligonucleotide fingerprint as tRNA (Pro), the primer for MuLV RNA-directed DNA synthesis. These results were obtained with two different MuLV strains, AKR and Moloney, each grown in SC-1 cells. The demonstration that ActD virions contain primer tRNA and in general exhibit the characteristic MuLV tRNA pattern rather than the complete representation of cell 4S RNA leads to the conclusion that genomic RNA is not the major determinant in selective packaging of host tRNA's. A possible role for one or more viral proteins, including reverse transcriptase, is suggested.", "contents": "Selective packaging of host tRNA's by murine leukemia virus particles does not require genomic RNA. The 4S RNA contained in RNA tumor virus particles consists of a selected population of host tRNA's. However, the mechanism by which virions select host tRNA's has not been elucidated. We have considered a model which specifies that 35S genomic RNA determines which tRNA's are to be encapsidated as well as the relative amounts of these tRNA's within the virion. The model was tested by comparing the free 4S RNA composition of normal murine leukemia virus (MuLV) particles and noninfectious virions from actinomycin D (ActD)-treated cells, which are deficient in genomic RNA (ActD virions). Viral 4S RNA was analyzed by two-dimensional polyacrylamide gel electrophoresis. Surprisingly, the patterns obtained for control and ActD 4S RNA were identical to each other and were clearly distinct from the cell 4S RNA pattern. The viral patterns had three prominent areas of radioactivity. One of the spots was identified on the basis of its oligonucleotide fingerprint as tRNA (Pro), the primer for MuLV RNA-directed DNA synthesis. These results were obtained with two different MuLV strains, AKR and Moloney, each grown in SC-1 cells. The demonstration that ActD virions contain primer tRNA and in general exhibit the characteristic MuLV tRNA pattern rather than the complete representation of cell 4S RNA leads to the conclusion that genomic RNA is not the major determinant in selective packaging of host tRNA's. A possible role for one or more viral proteins, including reverse transcriptase, is suggested."}
{"id": "PMID:219228", "title": "Oligosaccharide chains of avian RNA tumor virus glycoproteins contain heterogeneous oligomannosyl cores.", "content": "Chicken embryo fibroblasts (C/E phenotype) infected with subgroups B and C of the Prague strain of Rous sarcoma virus were radiolabeled with either [6-(3)H]-glucosamine or [2-(3)H]mannose, and virus was purified from the growth medium. The large envelope glycoprotein, gp85, was the only major radiolabeled component of purified virus. Pronase-digested glycopeptides from purified virus were analyzed by a combination of (i) gel filtration with columns of Sephadex G15/G50 and Bio-Gel P4 and (ii) enzymatic digestion of the oligosaccharide chains with specific exoglycosidases and endo-beta-N-acetylglucosaminidases. The rather broad molecular weight distribution (approximately 2,000 to 4,000) for glycopeptides in these studies and previous studies in other laboratories was shown to represent actual heterogeneity in the carbohydrate moieties: (i) the glycopeptides contained both mannose-rich, neutral chains and complex, acidic chains with terminal sialic acid; and (ii) both classes of asparagine-linked carbohydrate structures exhibited heterogeneity in the size of the oligomannosyl core (a mixture of approximately 5 to 9 mannose units for the neutral structures, and 3 or 5 mannose units for the acidic structures). With the [2-(3)H]mannose-labeled glycopeptides from Rous sarcoma virus, Prague strain subgroup C, most of the oligosaccharide chains were high-molecular-weight, acidic structures, with similar numbers of 3-mannose and 5-mannose core structures.", "contents": "Oligosaccharide chains of avian RNA tumor virus glycoproteins contain heterogeneous oligomannosyl cores. Chicken embryo fibroblasts (C/E phenotype) infected with subgroups B and C of the Prague strain of Rous sarcoma virus were radiolabeled with either [6-(3)H]-glucosamine or [2-(3)H]mannose, and virus was purified from the growth medium. The large envelope glycoprotein, gp85, was the only major radiolabeled component of purified virus. Pronase-digested glycopeptides from purified virus were analyzed by a combination of (i) gel filtration with columns of Sephadex G15/G50 and Bio-Gel P4 and (ii) enzymatic digestion of the oligosaccharide chains with specific exoglycosidases and endo-beta-N-acetylglucosaminidases. The rather broad molecular weight distribution (approximately 2,000 to 4,000) for glycopeptides in these studies and previous studies in other laboratories was shown to represent actual heterogeneity in the carbohydrate moieties: (i) the glycopeptides contained both mannose-rich, neutral chains and complex, acidic chains with terminal sialic acid; and (ii) both classes of asparagine-linked carbohydrate structures exhibited heterogeneity in the size of the oligomannosyl core (a mixture of approximately 5 to 9 mannose units for the neutral structures, and 3 or 5 mannose units for the acidic structures). With the [2-(3)H]mannose-labeled glycopeptides from Rous sarcoma virus, Prague strain subgroup C, most of the oligosaccharide chains were high-molecular-weight, acidic structures, with similar numbers of 3-mannose and 5-mannose core structures."}
{"id": "PMID:219229", "title": "Restricted replication of two alphaviruses in ricin-resistant mouse L cells with altered glycosyltransferase activities.", "content": "Two mouse L cell variant lines (CL 3 and CL 6) selected for resistance to the toxic plant lectin ricin were restricted in their ability to replicate the two alphaviruses Sindbis virus and Semliki Forest virus. CL 3 cells have been shown to exhibit increased CMP-sialic acid:glycoprotein sialyltransferase and GM3 synthetase activities, whereas CL 6 cells have been shown to contain decreased UDPgalactose:glycoprotein galactosyltransferase and UDP-N-acetylglucosamine:glycoprotein N-acetylglucosaminyltransferase activities. The adsorption of Sindbis virus to CL 6 cells was considerably reduced, suggesting that the loss or inaccessibility of the receptors for Sindbis virus accounted for a major defect in virus production in these cells. In contrast, CL 3 synthesized Sindbis viral RNA and proteins but were unable to convert the precursor glycoprotein PE2 to the structural protein E2. The cleavage of PE2 to E2 was also blocked in both CL 3 and CL 6 cells infected with Semliki Forest virus.", "contents": "Restricted replication of two alphaviruses in ricin-resistant mouse L cells with altered glycosyltransferase activities. Two mouse L cell variant lines (CL 3 and CL 6) selected for resistance to the toxic plant lectin ricin were restricted in their ability to replicate the two alphaviruses Sindbis virus and Semliki Forest virus. CL 3 cells have been shown to exhibit increased CMP-sialic acid:glycoprotein sialyltransferase and GM3 synthetase activities, whereas CL 6 cells have been shown to contain decreased UDPgalactose:glycoprotein galactosyltransferase and UDP-N-acetylglucosamine:glycoprotein N-acetylglucosaminyltransferase activities. The adsorption of Sindbis virus to CL 6 cells was considerably reduced, suggesting that the loss or inaccessibility of the receptors for Sindbis virus accounted for a major defect in virus production in these cells. In contrast, CL 3 synthesized Sindbis viral RNA and proteins but were unable to convert the precursor glycoprotein PE2 to the structural protein E2. The cleavage of PE2 to E2 was also blocked in both CL 3 and CL 6 cells infected with Semliki Forest virus."}
{"id": "PMID:219230", "title": "Poliovirus polyuridylic acid polymerase and RNA replicase have the same viral polypeptide.", "content": "A poliovirus-specific polyuridylic acid [poly(U)] polymerase that copies a polyadenylic acid template complexed to an oligouridylic acid primer was isolated from the membrane fraction of infected HeLa cells and was found to sediment at 4 to 5S on a linear 5 to 20% glycerol gradient. When the poly(U) polymerase was isolated from cells labeled with [(35)S]methionine and was analyzed by glycerol gradient centrifugation and polyacrylamide gel electrophoresis, the position of only one viral protein was found to correlate with the location of enzyme activity. This protein had an apparent molecular weight of 62,500 based on its electrophoretic mobility relative to that of several molecular weight standards and was designated p63. When the poly(U) polymerase was isolated from the soluble fraction of a cytoplasmic extract, the activity was found to sediment at about 7S. In this case, however, both p63 and NCVP2 (77,000-dalton precursor of p63) cosedimented with the 7S activity peak. When the 7S polymerase activity was purified by phosphocellulose chromatography, both p63 and NCVP2 were found to co-chromatograph with poly(U) polymerase activity. The poliovirus replicase complexed with its endogenous RNA template was isolated from infected cells labeled with [(35)S]methionine and was centrifuged through a linear 15 to 30% glycerol gradient. The major viral polypeptide component in a 26S peak of replicase activity was p63, but small amounts of other poliovirus proteins were also present. When the replicase-template complex was treated with RNase T1 before centrifugation, a single peak of activity was found that sedimented at 20S and contained only labeled p63. Thus, p63 was found to be the only viral polypeptide in the replicase bound to its endogenous RNA template, and appears to be active as a poly(U) polymerase either as a monomer protein or as a 7S complex.", "contents": "Poliovirus polyuridylic acid polymerase and RNA replicase have the same viral polypeptide. A poliovirus-specific polyuridylic acid [poly(U)] polymerase that copies a polyadenylic acid template complexed to an oligouridylic acid primer was isolated from the membrane fraction of infected HeLa cells and was found to sediment at 4 to 5S on a linear 5 to 20% glycerol gradient. When the poly(U) polymerase was isolated from cells labeled with [(35)S]methionine and was analyzed by glycerol gradient centrifugation and polyacrylamide gel electrophoresis, the position of only one viral protein was found to correlate with the location of enzyme activity. This protein had an apparent molecular weight of 62,500 based on its electrophoretic mobility relative to that of several molecular weight standards and was designated p63. When the poly(U) polymerase was isolated from the soluble fraction of a cytoplasmic extract, the activity was found to sediment at about 7S. In this case, however, both p63 and NCVP2 (77,000-dalton precursor of p63) cosedimented with the 7S activity peak. When the 7S polymerase activity was purified by phosphocellulose chromatography, both p63 and NCVP2 were found to co-chromatograph with poly(U) polymerase activity. The poliovirus replicase complexed with its endogenous RNA template was isolated from infected cells labeled with [(35)S]methionine and was centrifuged through a linear 15 to 30% glycerol gradient. The major viral polypeptide component in a 26S peak of replicase activity was p63, but small amounts of other poliovirus proteins were also present. When the replicase-template complex was treated with RNase T1 before centrifugation, a single peak of activity was found that sedimented at 20S and contained only labeled p63. Thus, p63 was found to be the only viral polypeptide in the replicase bound to its endogenous RNA template, and appears to be active as a poly(U) polymerase either as a monomer protein or as a 7S complex."}
{"id": "PMID:219231", "title": "Structural relationship between the 100,000- and 17,000- molecular-weight T antigens of simian virus 40 (SV40) as deduced by comparison with the SV40-specific proteins coded by the nondefective adenovirus type 2-SV40 hybrid viruses.", "content": "The two-dimensional peptide maps of the methionine-containing tryptic peptides of the 100,000-molecular-weight (100K) and 17K T antigens of simian virus 40 (SV40) have been compared. The two proteins share nine methionine-containing tryptic peptides in common. The 17K T antigen has two peptides not found in the 100K T antigen, and the 100K T antigen has 14 unique peptides. The peptide maps of the 100 K and 17K T antigens were also compared with those of the SV40-specific proteins found in cells infected by the nondefective adenovirus type 2-SV40 hybrid viruses, which we have previously shown are encoded by defined sequences within the early region of SV40 (K. Mann, T. Hunter, G. Walter, and H.K. Linke, J. Virol. 24:151-169, 1977). This comparison shows that the 100K and 17K T antigens share common N-terminal sequences coded for between 0.65 and 0.59 map units on the SV40 genome. Furthermore, none of the sequences in the 17K T antigen arises from the region between 0.54 and 0.18 map units. We deduce that the sequences unique to the 17K T antigen originate between 0.59 and 0.54 map units. This type of structural relationship between the 100K and 17K T antigens fits well with the proposed model (L.V. Crawford, C.N. Cole, A. E. Smith, E. Paucha, P. Tegtmeyer, K. Rundell, and P. Berg, Proc. Natl. Acad. Sci. U.S.A. 75:117-121, 1978) for the expression of the early region of SV40.", "contents": "Structural relationship between the 100,000- and 17,000- molecular-weight T antigens of simian virus 40 (SV40) as deduced by comparison with the SV40-specific proteins coded by the nondefective adenovirus type 2-SV40 hybrid viruses. The two-dimensional peptide maps of the methionine-containing tryptic peptides of the 100,000-molecular-weight (100K) and 17K T antigens of simian virus 40 (SV40) have been compared. The two proteins share nine methionine-containing tryptic peptides in common. The 17K T antigen has two peptides not found in the 100K T antigen, and the 100K T antigen has 14 unique peptides. The peptide maps of the 100 K and 17K T antigens were also compared with those of the SV40-specific proteins found in cells infected by the nondefective adenovirus type 2-SV40 hybrid viruses, which we have previously shown are encoded by defined sequences within the early region of SV40 (K. Mann, T. Hunter, G. Walter, and H.K. Linke, J. Virol. 24:151-169, 1977). This comparison shows that the 100K and 17K T antigens share common N-terminal sequences coded for between 0.65 and 0.59 map units on the SV40 genome. Furthermore, none of the sequences in the 17K T antigen arises from the region between 0.54 and 0.18 map units. We deduce that the sequences unique to the 17K T antigen originate between 0.59 and 0.54 map units. This type of structural relationship between the 100K and 17K T antigens fits well with the proposed model (L.V. Crawford, C.N. Cole, A. E. Smith, E. Paucha, P. Tegtmeyer, K. Rundell, and P. Berg, Proc. Natl. Acad. Sci. U.S.A. 75:117-121, 1978) for the expression of the early region of SV40."}
{"id": "PMID:219232", "title": "Gibbon ape leukemia virus-Hall's Island: new strain of gibbon ape leukemia virus.", "content": "Gibbon ape leukemia virus-Hall's Island (GaLV-H), a type C virus related to previous isolates of GaLV and simian sarcoma virus, was isolated from a gibbon ape with lymphocytic leukemia from a small colony of free-ranging gibbon apes on Hall's Island near Bermuda. We show here by molecular hybridization experiments that GaLV-H is approximately 60% related to three previous isolates of GaLV (GaLV-SF, GaLV-SEATO, and GaLV-Br) and is less closely related to simian sarcoma virus. The oligopyrimidine pattern of a transcript of the terminal 135 +/- 5 nucleotides of the viral RNA of GaLV-H is similar to that of GALV-Br but distinct from that of GaLV-SF and simian sarcoma virus. GaLV-H thus represents a fifth distinct strain of the infectious primate type C viruses, which among the previously described isolates of GaLV is most closely related to GaLV-Br.", "contents": "Gibbon ape leukemia virus-Hall's Island: new strain of gibbon ape leukemia virus. Gibbon ape leukemia virus-Hall's Island (GaLV-H), a type C virus related to previous isolates of GaLV and simian sarcoma virus, was isolated from a gibbon ape with lymphocytic leukemia from a small colony of free-ranging gibbon apes on Hall's Island near Bermuda. We show here by molecular hybridization experiments that GaLV-H is approximately 60% related to three previous isolates of GaLV (GaLV-SF, GaLV-SEATO, and GaLV-Br) and is less closely related to simian sarcoma virus. The oligopyrimidine pattern of a transcript of the terminal 135 +/- 5 nucleotides of the viral RNA of GaLV-H is similar to that of GALV-Br but distinct from that of GaLV-SF and simian sarcoma virus. GaLV-H thus represents a fifth distinct strain of the infectious primate type C viruses, which among the previously described isolates of GaLV is most closely related to GaLV-Br."}
{"id": "PMID:219233", "title": "Integration of Rous-associated virus type O provirus in susceptible chicken cells.", "content": "The number of viral genome equivalents per haploid cell genome was determined in normal chicken embryos from three selected chicken lines and in cultured fibroblasts (CEF) from these embryos. The cellular concentration of endogenous proviral DNA is similar in embryos from chickens of lines SPAFAS, 7, 15, 7 x 15, and 100. The concentration of proviral DNA is not affected by in vitro cultivation in CEF from lines that do not spontaneously produce virus, nor in CEF from line 7, which lacks receptors for Rous-associated virus type 0 (RAV-0). There is, however, a restricted increase in the number of integrated proviral genome equivalents in CEF from line 7 x 15, which produces RAV-0 and can support replication of this virus, and in CEF from line 15 experimentally infected with RAV-0.", "contents": "Integration of Rous-associated virus type O provirus in susceptible chicken cells. The number of viral genome equivalents per haploid cell genome was determined in normal chicken embryos from three selected chicken lines and in cultured fibroblasts (CEF) from these embryos. The cellular concentration of endogenous proviral DNA is similar in embryos from chickens of lines SPAFAS, 7, 15, 7 x 15, and 100. The concentration of proviral DNA is not affected by in vitro cultivation in CEF from lines that do not spontaneously produce virus, nor in CEF from line 7, which lacks receptors for Rous-associated virus type 0 (RAV-0). There is, however, a restricted increase in the number of integrated proviral genome equivalents in CEF from line 7 x 15, which produces RAV-0 and can support replication of this virus, and in CEF from line 15 experimentally infected with RAV-0."}
{"id": "PMID:219234", "title": "Persistence of herpes simplex virus type 1 in rat neurotumor cells.", "content": "Herpes simplex virus type 1 (HSV-1) infection of a rat central nervous system tumor cell line led to almost complete destruction of the cells. Cells that survived the infection could be isolated and shown to produce infectious HSV particles for variable lengths of time in culture ranging from 20 to 57 passages. Even though infectious virus production eventually ceased, the cell lines continued to produce herpes-specified proteins as measured by immunological techniques. These cells also showed herpesvirus-like structures in the electron microscope. The persistently infected cells that produced HSV antigens and bore HSV sequences were resistant to superinfection by HSV-1. The resistance was not due to failure of adsorption of the virus or to the production of interferon by the cells. The nature of the block in HSV replication in these neurotumor cells, which contain and partially express the HSV genome, is unknown, but may offer an interesting parallel to the known latency of HSV in neural tissues.", "contents": "Persistence of herpes simplex virus type 1 in rat neurotumor cells. Herpes simplex virus type 1 (HSV-1) infection of a rat central nervous system tumor cell line led to almost complete destruction of the cells. Cells that survived the infection could be isolated and shown to produce infectious HSV particles for variable lengths of time in culture ranging from 20 to 57 passages. Even though infectious virus production eventually ceased, the cell lines continued to produce herpes-specified proteins as measured by immunological techniques. These cells also showed herpesvirus-like structures in the electron microscope. The persistently infected cells that produced HSV antigens and bore HSV sequences were resistant to superinfection by HSV-1. The resistance was not due to failure of adsorption of the virus or to the production of interferon by the cells. The nature of the block in HSV replication in these neurotumor cells, which contain and partially express the HSV genome, is unknown, but may offer an interesting parallel to the known latency of HSV in neural tissues."}
{"id": "PMID:219235", "title": "Relationship between T-antigen and tumor-specific transplantation antigen in simian virus 40-transformed cells.", "content": "The simian virus 40 (sv40) tumor antigen (T-antigen) and tumor-specific transplantation antigen (TSTA) have been partially purified and studied to clarify their relationship. The T-antigen and the TSTA were partially purified from nuclei of SV AL/N cells, and SV40-transformed mouse embryo fibroblast line, by precipitation with ammonium sulfate and chromatography on DEAE- and DNA-cellulose. The T-antigen was assayed by complement fixation, and the TSTA was assayed by its ability to immunize mice against SV40-containing ascites tumor cells. When T-antigen- and TSTA-containing preparations were sedimented through sucrose gradients, each antigen had a major peak of activity at a sedimentation coefficient of 6.7 and minor peaks in other regions. Antiserum against T-antigen (from tumor-bearing hamsters) immunoprecipitated the TSTA activity. A preparation of T-antigen from human SV80 cells, which exhibited only one protein band after sodium dodecylsulfate-polyacrylamide gel electrophoresis, had TSTA activity when as little as 0.6 microgram of protein per mouse was used for immunization. These experiments demonstrate that the T-antigen, the product of the SV40 early A gene is capable of inducing specific immunity against transplantation of SV40-transformed tumor cells in mice.", "contents": "Relationship between T-antigen and tumor-specific transplantation antigen in simian virus 40-transformed cells. The simian virus 40 (sv40) tumor antigen (T-antigen) and tumor-specific transplantation antigen (TSTA) have been partially purified and studied to clarify their relationship. The T-antigen and the TSTA were partially purified from nuclei of SV AL/N cells, and SV40-transformed mouse embryo fibroblast line, by precipitation with ammonium sulfate and chromatography on DEAE- and DNA-cellulose. The T-antigen was assayed by complement fixation, and the TSTA was assayed by its ability to immunize mice against SV40-containing ascites tumor cells. When T-antigen- and TSTA-containing preparations were sedimented through sucrose gradients, each antigen had a major peak of activity at a sedimentation coefficient of 6.7 and minor peaks in other regions. Antiserum against T-antigen (from tumor-bearing hamsters) immunoprecipitated the TSTA activity. A preparation of T-antigen from human SV80 cells, which exhibited only one protein band after sodium dodecylsulfate-polyacrylamide gel electrophoresis, had TSTA activity when as little as 0.6 microgram of protein per mouse was used for immunization. These experiments demonstrate that the T-antigen, the product of the SV40 early A gene is capable of inducing specific immunity against transplantation of SV40-transformed tumor cells in mice."}
{"id": "PMID:219236", "title": "Herpes simplex virus type 2 functions expressed during stimulation of human cell DNA synthesis.", "content": "Experiments were designed to identify herpes simplex virus type 2 (HSV-2)-specific functions expressed during stimulation of human embryo fibroblast DNA synthesis. Cultures were partially arrested in DNA synthesis by pretreatment with 5-fluorouracil and maintenance in low-serum (0.2%) medium during virus infection. Results showed that continuous [methyl-(3)H]thymidine uptake into cellular DNA was ninefold greater in HSV-2-infected than in mock-infected cultures measured after 24 h of incubation at 42 degrees C. Shifting mock-infected cultures from low- to high-serum (10%) medium also caused some stimulation, but [methyl-(3)H]thymidine uptake was only twofold greater than in cells maintained with low serum. Plating efficiencies of both HSV-2-infected and mock-infected cells at 42 degrees C were essentially the same and ranged from 37 to 76% between zero time and 72 h of incubation. De novo RNA and protein syntheses were continuously required for HSV-2 stimulation of cellular DNA synthesis. HSV-2 infection markedly enhanced transport, phosphorylation, and rate of incorporation of [methyl-(3)H]thymidine into cellular DNA, starting at 3 h and reaching a maximum by 12 h; after 12 h, these processes gradually declined to low levels. In mock-infected cells these processes remained at low levels throughout the observation period. Pretreatment of cells with interferon or addition of arabinofuranosylthymine at the time of virus infection inhibited stimulation caused by HSV-2. 5-Bromodeoxyuridine density-labeled experiments revealed that HSV-2 stimulates predominantly semiconservative DNA replication and some DNA repair. Stimulation of [methyl-(3)H]thymidine into cellular DNA correlated with detection of virus-specific thymidine kinase activity. In conclusion, HSV-2 stimulation of cellular DNA synthesis appeared to involve at least four virus-specific functions: induction of thymidine transport, HSV-2 thymidine kinase activity, semiconservative replication, and repair of cellular DNA.", "contents": "Herpes simplex virus type 2 functions expressed during stimulation of human cell DNA synthesis. Experiments were designed to identify herpes simplex virus type 2 (HSV-2)-specific functions expressed during stimulation of human embryo fibroblast DNA synthesis. Cultures were partially arrested in DNA synthesis by pretreatment with 5-fluorouracil and maintenance in low-serum (0.2%) medium during virus infection. Results showed that continuous [methyl-(3)H]thymidine uptake into cellular DNA was ninefold greater in HSV-2-infected than in mock-infected cultures measured after 24 h of incubation at 42 degrees C. Shifting mock-infected cultures from low- to high-serum (10%) medium also caused some stimulation, but [methyl-(3)H]thymidine uptake was only twofold greater than in cells maintained with low serum. Plating efficiencies of both HSV-2-infected and mock-infected cells at 42 degrees C were essentially the same and ranged from 37 to 76% between zero time and 72 h of incubation. De novo RNA and protein syntheses were continuously required for HSV-2 stimulation of cellular DNA synthesis. HSV-2 infection markedly enhanced transport, phosphorylation, and rate of incorporation of [methyl-(3)H]thymidine into cellular DNA, starting at 3 h and reaching a maximum by 12 h; after 12 h, these processes gradually declined to low levels. In mock-infected cells these processes remained at low levels throughout the observation period. Pretreatment of cells with interferon or addition of arabinofuranosylthymine at the time of virus infection inhibited stimulation caused by HSV-2. 5-Bromodeoxyuridine density-labeled experiments revealed that HSV-2 stimulates predominantly semiconservative DNA replication and some DNA repair. Stimulation of [methyl-(3)H]thymidine into cellular DNA correlated with detection of virus-specific thymidine kinase activity. In conclusion, HSV-2 stimulation of cellular DNA synthesis appeared to involve at least four virus-specific functions: induction of thymidine transport, HSV-2 thymidine kinase activity, semiconservative replication, and repair of cellular DNA."}
{"id": "PMID:219237", "title": "Characterization of some isolates of newly recovered avian sarcoma virus.", "content": "We previously reported the isolation of a newly recovered avian sarcoma virus (rASV) from tumors of chickens injected with transformation-defective (td) mutants of the Schmidt-Ruppin strain of Rous sarcoma virus (SR-RSV). In this paper, we present further biological and biochemical characterization of the recovered sarcoma viruses. High titers of rASV's were generally obtained by cocultivation of tumor cells with normal chicken embryo fibroblasts or by homogenization of tumor tissues. Most rASV isolates were similar to SR-RSV, subgroup A (SR-RSV-A), in their growth characteristics and were nondefective in replication. The subgroup specificity of rASV's and the electrophoretic mobilities of their structural proteins were the same as those parental td viruses. The nondefectiveness of rASV's was further substantiated by the size of their genomic RNA, which was indistinguishable from that of SR-RSV-A and substantially larger than that of parental td RNA. Molecular hybridization using complementary DNA specific to the src gene of SR-RSV (cDNAsrc) showed that the RNAs of td mutants used in this study contained extensive deletions within the src gene (7 to 30% hybridization with cDNAsrc); the same probe hybridized up to 90% with RNA from two isolates of rASV. These data indicate that rASV has regained genetic information which had been deleted in the td mutants and strongly suggest that the generation of rASV involves a genetic interaction between td virus and host cell genetic information.", "contents": "Characterization of some isolates of newly recovered avian sarcoma virus. We previously reported the isolation of a newly recovered avian sarcoma virus (rASV) from tumors of chickens injected with transformation-defective (td) mutants of the Schmidt-Ruppin strain of Rous sarcoma virus (SR-RSV). In this paper, we present further biological and biochemical characterization of the recovered sarcoma viruses. High titers of rASV's were generally obtained by cocultivation of tumor cells with normal chicken embryo fibroblasts or by homogenization of tumor tissues. Most rASV isolates were similar to SR-RSV, subgroup A (SR-RSV-A), in their growth characteristics and were nondefective in replication. The subgroup specificity of rASV's and the electrophoretic mobilities of their structural proteins were the same as those parental td viruses. The nondefectiveness of rASV's was further substantiated by the size of their genomic RNA, which was indistinguishable from that of SR-RSV-A and substantially larger than that of parental td RNA. Molecular hybridization using complementary DNA specific to the src gene of SR-RSV (cDNAsrc) showed that the RNAs of td mutants used in this study contained extensive deletions within the src gene (7 to 30% hybridization with cDNAsrc); the same probe hybridized up to 90% with RNA from two isolates of rASV. These data indicate that rASV has regained genetic information which had been deleted in the td mutants and strongly suggest that the generation of rASV involves a genetic interaction between td virus and host cell genetic information."}
{"id": "PMID:219238", "title": "Herpes simplex virus type 1 Angelotti and a defective viral genotype: analysis of genome structures and genetic relatedness by DNA-DNA reassociation kinetics.", "content": "DNA-DNA reassociation kinetics of herpes simplex virus type 1 Angelotti DNA and a class of defective viral DNA revealed that the viral standard genome has a total sequence complexity of about 93 X 10(6) daltons and that a portion of 11 X 10(6) daltons occurs twice on the viral genome. These results agree with structural features of herpes simplex virus type 1 DNA derived from electron microscopic studies and restriction enzyme analyses by several investigators. The defective viral DNA (molecular weight, about 97 X 10(6)) displays a sequence complexity of about 11 X 10(6) daltons, suggesting that the molecule is built up by repetitions of standard DNA sequences comprising about 15,000 base pairs. A 2 X 10(6)-dalton portion of these sequences maps in the redundant region and a 9 X 10(6)-dalton portion maps in the unique part of the standard herpes simplex virus type 1 Angelotti DNA, as could be shown by reassociation of viral standard DNA in the presence of defective DNA and vice versa. No cellular DNA sequences could be detected in defective DNA. A 12% molar fraction of the defective DNA consists of highly repetitive sequences of about 350 to 500 base pairs in length.", "contents": "Herpes simplex virus type 1 Angelotti and a defective viral genotype: analysis of genome structures and genetic relatedness by DNA-DNA reassociation kinetics. DNA-DNA reassociation kinetics of herpes simplex virus type 1 Angelotti DNA and a class of defective viral DNA revealed that the viral standard genome has a total sequence complexity of about 93 X 10(6) daltons and that a portion of 11 X 10(6) daltons occurs twice on the viral genome. These results agree with structural features of herpes simplex virus type 1 DNA derived from electron microscopic studies and restriction enzyme analyses by several investigators. The defective viral DNA (molecular weight, about 97 X 10(6)) displays a sequence complexity of about 11 X 10(6) daltons, suggesting that the molecule is built up by repetitions of standard DNA sequences comprising about 15,000 base pairs. A 2 X 10(6)-dalton portion of these sequences maps in the redundant region and a 9 X 10(6)-dalton portion maps in the unique part of the standard herpes simplex virus type 1 Angelotti DNA, as could be shown by reassociation of viral standard DNA in the presence of defective DNA and vice versa. No cellular DNA sequences could be detected in defective DNA. A 12% molar fraction of the defective DNA consists of highly repetitive sequences of about 350 to 500 base pairs in length."}
{"id": "PMID:219239", "title": "Noninfectious vesicular stomatitis virus particles deficient in the viral nucleocapsid.", "content": "Several temperature-sensitive mutants of vesicular stomatitis virus in complementation group III produce, at nonpermissive temperature, noninfectious particles which contain the viral M (matrix) and G (glycoprotein) proteins but less than 10% of the normal proportion of N protein or RNA. Since group III mutants are thought to be defective in the structural gene for the virus M protein, these findings demonstrate that an interaction between M and the nucleocapsid is of importance in virus budding. Taken together with earlier results, they suggest that M is the key protein in bud formation.", "contents": "Noninfectious vesicular stomatitis virus particles deficient in the viral nucleocapsid. Several temperature-sensitive mutants of vesicular stomatitis virus in complementation group III produce, at nonpermissive temperature, noninfectious particles which contain the viral M (matrix) and G (glycoprotein) proteins but less than 10% of the normal proportion of N protein or RNA. Since group III mutants are thought to be defective in the structural gene for the virus M protein, these findings demonstrate that an interaction between M and the nucleocapsid is of importance in virus budding. Taken together with earlier results, they suggest that M is the key protein in bud formation."}
{"id": "PMID:219240", "title": "Anatomy of herpes simplex virus DNA. XII. Accumulation of head-to-tail concatemers in nuclei of infected cells and their role in the generation of the four isomeric arrangements of viral DNA.", "content": "Previous reports (H. Delius and J. B. Clements, J. Gen. Virol. 33:125-134, 1976; G. S. Hayward, R. J. Jacob, S. C. Wadsworth, and B. Roizman, Proc. Natl. Acad. Sci. U.S.A. 72:4243-4247, 1975; B. Roizman, G. S. Hayward, R. Jacob, S. W. Wadsworth, and R. W. Honess, Excerpta Med. Int. Congr. Ser. 2:188-198, 1974) have shown that herpes simplex virus DNA extracted from virions accumulating in the cytoplasm of infected cells consists of four populations of linear molecules differing in the orientation of the covalently linked large (L) and small (S) components relative to each other. Together, these four isomeric arrangements of viral DNA display four different termini and four different L-S component junctions. In the studies reported in this paper, we analyzed with restriction endonucleases the newly replicated viral DNA shortly after the onset of viral DNA synthesis, the progeny DNA accumulating in the nuclei late in infection, and rapidly sedimenting DNA present in nuclei of infected cells at 8 h after infection. In each instance the nuclear viral DNA contained a decreased concentration of all four terminal fragments and an increase in the concentration of fragments spanning the junction of L and S components relative to the concentration of other DNA fragments. The results are consistent with the hypothesis that the viral DNA accumulating in the nuclei consists of head-to-tail concatemers arising from the replication of DNA by a rolling-circle mechanism. A model is presented for generation of all four isomeric arrangements of herpes simplex virus DNA from one arrangement based on excision and repair of unit length DNA from head-to-tail concatemers and known features of the sequence arrangement of viral DNA.", "contents": "Anatomy of herpes simplex virus DNA. XII. Accumulation of head-to-tail concatemers in nuclei of infected cells and their role in the generation of the four isomeric arrangements of viral DNA. Previous reports (H. Delius and J. B. Clements, J. Gen. Virol. 33:125-134, 1976; G. S. Hayward, R. J. Jacob, S. C. Wadsworth, and B. Roizman, Proc. Natl. Acad. Sci. U.S.A. 72:4243-4247, 1975; B. Roizman, G. S. Hayward, R. Jacob, S. W. Wadsworth, and R. W. Honess, Excerpta Med. Int. Congr. Ser. 2:188-198, 1974) have shown that herpes simplex virus DNA extracted from virions accumulating in the cytoplasm of infected cells consists of four populations of linear molecules differing in the orientation of the covalently linked large (L) and small (S) components relative to each other. Together, these four isomeric arrangements of viral DNA display four different termini and four different L-S component junctions. In the studies reported in this paper, we analyzed with restriction endonucleases the newly replicated viral DNA shortly after the onset of viral DNA synthesis, the progeny DNA accumulating in the nuclei late in infection, and rapidly sedimenting DNA present in nuclei of infected cells at 8 h after infection. In each instance the nuclear viral DNA contained a decreased concentration of all four terminal fragments and an increase in the concentration of fragments spanning the junction of L and S components relative to the concentration of other DNA fragments. The results are consistent with the hypothesis that the viral DNA accumulating in the nuclei consists of head-to-tail concatemers arising from the replication of DNA by a rolling-circle mechanism. A model is presented for generation of all four isomeric arrangements of herpes simplex virus DNA from one arrangement based on excision and repair of unit length DNA from head-to-tail concatemers and known features of the sequence arrangement of viral DNA."}
{"id": "PMID:219241", "title": "Evidence that the RNA polymerase usually does not make a complete transcript of the late strand of simian virus 40 DNA.", "content": "An important model for the transcription of the late (L) strand of simian virus 40 DNA is that, late after infection of permissive monkey cells, the RNA polymerase makes a complete transcript of the L DNA strand before terminating transcription. The purpose of the current work was to test a prediction of this model, namely, that the rate of synthesis of all RNA sequences from the L DNA strand should be equal. About one-half of the L DNA strand is transcribed into late mRNA sequences and the other half into late dRNA sequences, which do not leave the nucleus. Using glucosamine to reduce the size of the intracellular UTP pool before and after a pulse-label with radioactive uridine, a pulse-chase experiment was performed to determine the half-lives of these sequences. The half-life of the late dRNA sequences was determined to be 4 min. The late mRNA sequences were degraded more slowly, on the average, than the late dRNA sequences. In a parallel experiment with similarly treated cells, it was shown that after a 2-min label with radioactive uridine there was only 0.2 times as much radioactivity in the late dRNA sequences as in the late mRNA sequences in the total cellular RNA population. The results could be combined to calculate that the rate of synthesis of the late dRNA sequences was at most 0.3 times that of the late mRNA sequences. Consequently they provide strong evidence that when the RNA polymerase transcribes the late mRNA sequences, it usually terminates transcription before all the late dRNA sequences are transcribed.", "contents": "Evidence that the RNA polymerase usually does not make a complete transcript of the late strand of simian virus 40 DNA. An important model for the transcription of the late (L) strand of simian virus 40 DNA is that, late after infection of permissive monkey cells, the RNA polymerase makes a complete transcript of the L DNA strand before terminating transcription. The purpose of the current work was to test a prediction of this model, namely, that the rate of synthesis of all RNA sequences from the L DNA strand should be equal. About one-half of the L DNA strand is transcribed into late mRNA sequences and the other half into late dRNA sequences, which do not leave the nucleus. Using glucosamine to reduce the size of the intracellular UTP pool before and after a pulse-label with radioactive uridine, a pulse-chase experiment was performed to determine the half-lives of these sequences. The half-life of the late dRNA sequences was determined to be 4 min. The late mRNA sequences were degraded more slowly, on the average, than the late dRNA sequences. In a parallel experiment with similarly treated cells, it was shown that after a 2-min label with radioactive uridine there was only 0.2 times as much radioactivity in the late dRNA sequences as in the late mRNA sequences in the total cellular RNA population. The results could be combined to calculate that the rate of synthesis of the late dRNA sequences was at most 0.3 times that of the late mRNA sequences. Consequently they provide strong evidence that when the RNA polymerase transcribes the late mRNA sequences, it usually terminates transcription before all the late dRNA sequences are transcribed."}
{"id": "PMID:219242", "title": "Effect of 5-methylcytidine on virus production in avian sarcoma virus-infected chicken embryo cells.", "content": "5-Methylcytidine (5mC) is a minor constituent of RNA in procaryotes as well as eucaryotes. The function of this modified nucleoside is not known. We studied the effect of this compound on virus production in avian sarcoma virus-infected chicken embryo fibroblasts. We found, surprisingly, that virus release into the medium was severely reduced in cultures treated with 5mC. In contrast to the effect of 5mC on virus release, intracellular levels of virus-specific RNA transcripts as well as the proteins were slightly elevated. Analysis of intracellular RNA transcripts on velocity gradients and virus-specific proteins in polyacrylamide gels did not reveal any qualitative differences in 5mC-treated cells compared to cytidine-treated cells. From these results we conclude that the effect of 5mC is probably at the level of virus maturation or packaging.", "contents": "Effect of 5-methylcytidine on virus production in avian sarcoma virus-infected chicken embryo cells. 5-Methylcytidine (5mC) is a minor constituent of RNA in procaryotes as well as eucaryotes. The function of this modified nucleoside is not known. We studied the effect of this compound on virus production in avian sarcoma virus-infected chicken embryo fibroblasts. We found, surprisingly, that virus release into the medium was severely reduced in cultures treated with 5mC. In contrast to the effect of 5mC on virus release, intracellular levels of virus-specific RNA transcripts as well as the proteins were slightly elevated. Analysis of intracellular RNA transcripts on velocity gradients and virus-specific proteins in polyacrylamide gels did not reveal any qualitative differences in 5mC-treated cells compared to cytidine-treated cells. From these results we conclude that the effect of 5mC is probably at the level of virus maturation or packaging."}
{"id": "PMID:219243", "title": "Murine mammary tumor virus expression during mammary tumorigenesis in BALB/c mice.", "content": "Steady-state levels of murine mammary tumor virus (MuMTV) RNA were quantitated during mammary tumorigenesis in BALB/c mice by molecular hybridization with a representative MuMTV complementary DNA (cDNA) probe. Hyperplastic alveolar nodule (HAN) lines are preneoplastic mammary lesions that were induced in BALB/c mice by hormones alone or in combination with 7,12-dimethylbenz(a)anthracene and give rise to mammary tumors. The hormone-induced HAN lines D1 and D2 contained detectable amounts of hybridizable MuMTV sequences. MuMTV RNA sequences were also observed in five of the six transplanted BALB/c mammary tumors that were examined. Similar levels of hybridizable MuMTV RNA were observed between the D1 or D2 HAN line and mammary tumors derived from each HAN line. The D2 HAN line as well as D2, C4, and CD8 mammary tumors accumulated RNA that was apparently homologous to most of the MuMTV genome. Thermal denaturation of hybrids indicated extensive sequence homology between the MuMTV cDNA and hybridizable RNA in the BALB/c HAN lines and mammary tumors. A low level of type C viral RNA was observed in the BALB/c HAN lines and most mammary tumors by molecular hybridization with a cDNA to Moloney murine leukemia virus. These data demonstrate that MuMTV sequences are frequently expressed in hormone-induced BALB/c HAN lines and mammary tumors derived from HAN lines or ductal hyperplasias induced in BALB/c mice by hormones and/or a chemical carcinogen. The transition from the preneoplastic to the neoplastic state in BALB/c mice does not appear to be due to a change in the steady-state levels of MuMTV RNA since the hormone-induced HAN lines and mammary tumors had similar levels of hybridizable MuMTV RNA.", "contents": "Murine mammary tumor virus expression during mammary tumorigenesis in BALB/c mice. Steady-state levels of murine mammary tumor virus (MuMTV) RNA were quantitated during mammary tumorigenesis in BALB/c mice by molecular hybridization with a representative MuMTV complementary DNA (cDNA) probe. Hyperplastic alveolar nodule (HAN) lines are preneoplastic mammary lesions that were induced in BALB/c mice by hormones alone or in combination with 7,12-dimethylbenz(a)anthracene and give rise to mammary tumors. The hormone-induced HAN lines D1 and D2 contained detectable amounts of hybridizable MuMTV sequences. MuMTV RNA sequences were also observed in five of the six transplanted BALB/c mammary tumors that were examined. Similar levels of hybridizable MuMTV RNA were observed between the D1 or D2 HAN line and mammary tumors derived from each HAN line. The D2 HAN line as well as D2, C4, and CD8 mammary tumors accumulated RNA that was apparently homologous to most of the MuMTV genome. Thermal denaturation of hybrids indicated extensive sequence homology between the MuMTV cDNA and hybridizable RNA in the BALB/c HAN lines and mammary tumors. A low level of type C viral RNA was observed in the BALB/c HAN lines and most mammary tumors by molecular hybridization with a cDNA to Moloney murine leukemia virus. These data demonstrate that MuMTV sequences are frequently expressed in hormone-induced BALB/c HAN lines and mammary tumors derived from HAN lines or ductal hyperplasias induced in BALB/c mice by hormones and/or a chemical carcinogen. The transition from the preneoplastic to the neoplastic state in BALB/c mice does not appear to be due to a change in the steady-state levels of MuMTV RNA since the hormone-induced HAN lines and mammary tumors had similar levels of hybridizable MuMTV RNA."}
{"id": "PMID:219244", "title": "Rescue and transmission of a replication-defective variant of moloney murine leukemia virus.", "content": "We have described a clone of mouse cells, termed \"8A,\" which appears to be infected with a replication-defective variant of Moloney murine leukemia virus (MuLV) (Rein et al., J. Virol. 25:146-156, 1978). Clone 8A cells release virus particles which do not form plaques in the standard XC test. However, approximately 10(2) particles per ml of clone 8A supernatant do form plaques in a modified XC test (the \"complementation plaque assay\"), in which the assay cells are coinfected with the XC-negative, nondefective amphotropic MuLV as well as the test virus. Superinfection of clone 8A cells themselves with amphotropic MuLV results in the production of approximately 10(5), rather than approximately 10(2), particles per ml which register in the complementation plaque assay. This increase is due to the rescue of replication-defective ecotropic MuLV from clone 8A cells by amphotropic MuLV since (i) this ecotropic MuLV can only form XC plaques in cells which are coinfected with amphotropic MuLV; and (ii) it is possible to transmit this defective variant, rescued from superinfected clone 8A cells, to a fresh clone of normal mouse cells. The time course of production of the rescued MuLV particles by superinfected clone 8A cells is virtually identical to that of rescue from these cells of murine sarcoma virus. Amphotropic MuLV superinfection of \"NP-N\" cells, which contain a \"non-plaque-forming\" variant of N-tropic MuLV (Hopkins and Jolicoeur, J. Virol. 16:991-999, 1975), also increases the titer of particles registering in the complementation plaque assay; thus, NP-N cells, like clone 8A cells, contain a rescuable defective variant of ecotropic MuLV.", "contents": "Rescue and transmission of a replication-defective variant of moloney murine leukemia virus. We have described a clone of mouse cells, termed \"8A,\" which appears to be infected with a replication-defective variant of Moloney murine leukemia virus (MuLV) (Rein et al., J. Virol. 25:146-156, 1978). Clone 8A cells release virus particles which do not form plaques in the standard XC test. However, approximately 10(2) particles per ml of clone 8A supernatant do form plaques in a modified XC test (the \"complementation plaque assay\"), in which the assay cells are coinfected with the XC-negative, nondefective amphotropic MuLV as well as the test virus. Superinfection of clone 8A cells themselves with amphotropic MuLV results in the production of approximately 10(5), rather than approximately 10(2), particles per ml which register in the complementation plaque assay. This increase is due to the rescue of replication-defective ecotropic MuLV from clone 8A cells by amphotropic MuLV since (i) this ecotropic MuLV can only form XC plaques in cells which are coinfected with amphotropic MuLV; and (ii) it is possible to transmit this defective variant, rescued from superinfected clone 8A cells, to a fresh clone of normal mouse cells. The time course of production of the rescued MuLV particles by superinfected clone 8A cells is virtually identical to that of rescue from these cells of murine sarcoma virus. Amphotropic MuLV superinfection of \"NP-N\" cells, which contain a \"non-plaque-forming\" variant of N-tropic MuLV (Hopkins and Jolicoeur, J. Virol. 16:991-999, 1975), also increases the titer of particles registering in the complementation plaque assay; thus, NP-N cells, like clone 8A cells, contain a rescuable defective variant of ecotropic MuLV."}
{"id": "PMID:219245", "title": "Genes controlling receptors for ecotropic and xenotropic type C virus in Mus cervicolor and Mus musculus.", "content": "Gene loci controlling cell surface receptors for murine leukemia virus were studied by using murine X Chinese hamster hybrid cells. Hybrids which exclusively segregate murine chromosomes were made by fusing Mus cervicolor and Mus musculus lymphocytes to hamster fibroblasts. Sensitivity to Moloney murine leukemia virus infecotion and specific binding of the envelope glycoprotein of Rauscher murine leukemia virus (gp70) cosegregate and isozyme analysis show an association with chromosome 5 in both species. With the possible exception of one clone, no evidence was found for a proviral integration site independent of chromosome 5. Evidence is presented for additional unlinked ectropic and xenotropic receptors independent of chromosome 5.", "contents": "Genes controlling receptors for ecotropic and xenotropic type C virus in Mus cervicolor and Mus musculus. Gene loci controlling cell surface receptors for murine leukemia virus were studied by using murine X Chinese hamster hybrid cells. Hybrids which exclusively segregate murine chromosomes were made by fusing Mus cervicolor and Mus musculus lymphocytes to hamster fibroblasts. Sensitivity to Moloney murine leukemia virus infecotion and specific binding of the envelope glycoprotein of Rauscher murine leukemia virus (gp70) cosegregate and isozyme analysis show an association with chromosome 5 in both species. With the possible exception of one clone, no evidence was found for a proviral integration site independent of chromosome 5. Evidence is presented for additional unlinked ectropic and xenotropic receptors independent of chromosome 5."}
{"id": "PMID:219246", "title": "Nature of Rous sarcoma virus-specific RNA in transformed and revertant field vole cells.", "content": "Cytoplasmic and polyribosomal RNAs from Rous sarcoma virus-transformed and phenotypically reverted field vole cells were fractionated by rate-zonal sedimentation and hybridized with a (3)H-labeled complementary DNA viral probe to determine the size classes of virus-specific RNA present in these cell types. In contrast to Rous sarcoma virus-infected permissive avian cells, only two of three discrete species of virus-specific RNA were detected in the cytoplasm of these vole cells. These included genome-length 35S RNA and a 21S RNA. However, viral 28S RNA, routinely detected in the cytoplasm of productively infected avian cells, could not be found in cytoplasmic RNA from vole cells. In addition, a low-molecular-weight viral RNA sedimenting less than 16S was detected in both infected avian and vole cells. Because of its heterogeneity this latter species is most likely generated from the intracellular degradation of the larger viral RNAs. Both the viral 35S and 21S RNA were also found to be associated with total polyribosomes from these vole cells. Studies were also performed to determine the distribution of both total viral genomic and sarcoma-specific RNA sequences among the size classes of fractionated total polyribosomes. In both vole cell types the majority of cytoplasmic viral RNA sequences were also associated with polyribosomes and were similarly distributed among the size classes of total polyribosomes. Sarcoma-specific sequences were present on both the 35S and 21S RNA species. These data suggest that the expression of the viral transforming gene in revertant field vole cells may be controlled at some stage subsequent to translation of the viral RNA.", "contents": "Nature of Rous sarcoma virus-specific RNA in transformed and revertant field vole cells. Cytoplasmic and polyribosomal RNAs from Rous sarcoma virus-transformed and phenotypically reverted field vole cells were fractionated by rate-zonal sedimentation and hybridized with a (3)H-labeled complementary DNA viral probe to determine the size classes of virus-specific RNA present in these cell types. In contrast to Rous sarcoma virus-infected permissive avian cells, only two of three discrete species of virus-specific RNA were detected in the cytoplasm of these vole cells. These included genome-length 35S RNA and a 21S RNA. However, viral 28S RNA, routinely detected in the cytoplasm of productively infected avian cells, could not be found in cytoplasmic RNA from vole cells. In addition, a low-molecular-weight viral RNA sedimenting less than 16S was detected in both infected avian and vole cells. Because of its heterogeneity this latter species is most likely generated from the intracellular degradation of the larger viral RNAs. Both the viral 35S and 21S RNA were also found to be associated with total polyribosomes from these vole cells. Studies were also performed to determine the distribution of both total viral genomic and sarcoma-specific RNA sequences among the size classes of fractionated total polyribosomes. In both vole cell types the majority of cytoplasmic viral RNA sequences were also associated with polyribosomes and were similarly distributed among the size classes of total polyribosomes. Sarcoma-specific sequences were present on both the 35S and 21S RNA species. These data suggest that the expression of the viral transforming gene in revertant field vole cells may be controlled at some stage subsequent to translation of the viral RNA."}
{"id": "PMID:219247", "title": "Precipitation of visna viral proteins by immune sera of rabbits and sheep.", "content": "Eighteen polypeptides equivalent to 1.2 x 10(6) daltons of visna virus were specifically precipitated by immune sera from rabbits and sheep. The hyperimmunized rabbit antisera contained high concentrations of antibodies against p25 and p14, whereas the sera from sheep actively infected with visna virus showed a large quantity of anti-gp115 antibody. The results indicate that almost all the polypeptides reported previously (F. H. Lin, J. Virol. 25:207--214, 1978) are virus-specific components of visna. The presence of anti-gp115 antibody in sera of infected sheep may offer a simple and sensitive diagnostic procedure for visna.", "contents": "Precipitation of visna viral proteins by immune sera of rabbits and sheep. Eighteen polypeptides equivalent to 1.2 x 10(6) daltons of visna virus were specifically precipitated by immune sera from rabbits and sheep. The hyperimmunized rabbit antisera contained high concentrations of antibodies against p25 and p14, whereas the sera from sheep actively infected with visna virus showed a large quantity of anti-gp115 antibody. The results indicate that almost all the polypeptides reported previously (F. H. Lin, J. Virol. 25:207--214, 1978) are virus-specific components of visna. The presence of anti-gp115 antibody in sera of infected sheep may offer a simple and sensitive diagnostic procedure for visna."}
{"id": "PMID:219248", "title": "Effect of alkylation on the physical properties of simian virus 40 T-antigen species.", "content": "We analyzed large and small species of T-antigen by immunoprecipitation and two-dimensional gel electrophoresis. The T-antigen species were subjected to electrophoresis either directly or after reduction and alkylation with N-ethylmaleimide. Treatment with N-ethylmaleimide improved the resolution of large-T by two-dimensional gel electrophoresis and was a requirement for the resolution of small-t antigen on two dimensional gels. Large-T did not form a discrete protein spot, but rather formed a streak from approximately pH 6.5 to 6.9 on isoelectric focusing gels. Small-t formed a sharp protein spot at approximately pH 7.2 when subjected to electrophoresis under non-equilibrium conditions which extended the pH gradient to include proteins with basic isoelectric points. Treatment with N-ethylmaleimide decreased the mobility of the T-antigen species during sodium dodecyl sulfate gel electrophoresis. We suggest that the apparent increase in molecular weight was due to the association of N-ethylmaleimide with cysteine-rich regions of these proteins. Viable deletion mutants of simian virus 40 which do not induce the synthesis of small-t but product small-t-related polypeptides were used to localize the cysteine-rich region of small-t to between 0.54 and 0.59 on the genetic map of simian virus 40.", "contents": "Effect of alkylation on the physical properties of simian virus 40 T-antigen species. We analyzed large and small species of T-antigen by immunoprecipitation and two-dimensional gel electrophoresis. The T-antigen species were subjected to electrophoresis either directly or after reduction and alkylation with N-ethylmaleimide. Treatment with N-ethylmaleimide improved the resolution of large-T by two-dimensional gel electrophoresis and was a requirement for the resolution of small-t antigen on two dimensional gels. Large-T did not form a discrete protein spot, but rather formed a streak from approximately pH 6.5 to 6.9 on isoelectric focusing gels. Small-t formed a sharp protein spot at approximately pH 7.2 when subjected to electrophoresis under non-equilibrium conditions which extended the pH gradient to include proteins with basic isoelectric points. Treatment with N-ethylmaleimide decreased the mobility of the T-antigen species during sodium dodecyl sulfate gel electrophoresis. We suggest that the apparent increase in molecular weight was due to the association of N-ethylmaleimide with cysteine-rich regions of these proteins. Viable deletion mutants of simian virus 40 which do not induce the synthesis of small-t but product small-t-related polypeptides were used to localize the cysteine-rich region of small-t to between 0.54 and 0.59 on the genetic map of simian virus 40."}
{"id": "PMID:219249", "title": "In vitro, the major ribosome binding site on Rous sarcoma virus RNA does not contain the nucleotide sequence coding for the N-terminal amino acids of the gag gene product.", "content": "Ribosomes from the reticulocyte lysate bind strongly and mainly to a region located in the 5' end of the Rous sarcoma virus RNA molecule between residues 9 and 53. This binding involves the participation of initiator tRNA and is sensitive to inhibitors of initiation of protein synthesis such as 7-methyl-GMP and aurintricarboxylic acid. The nucleotide sequence of this ribosome binding site has been determined: it conatains a GUG codon centered at position 26 that is not in phase with any termination codon within the 5' end nucleotide sequence of the RNA that we have analyzed (101 residues). However, the predicted N-terminal amino acid sequence starting from this GUG codon (or even from any AUG or GUG codon in the 5' end of the RNA) does not coincide with that of the in vitro-synthesized product of the 5' end proximal gag gene. Nevertheless, inhibition of ribosome binding to this site is accompanied by an inhibition of the in vitro translation of the gag gene.", "contents": "In vitro, the major ribosome binding site on Rous sarcoma virus RNA does not contain the nucleotide sequence coding for the N-terminal amino acids of the gag gene product. Ribosomes from the reticulocyte lysate bind strongly and mainly to a region located in the 5' end of the Rous sarcoma virus RNA molecule between residues 9 and 53. This binding involves the participation of initiator tRNA and is sensitive to inhibitors of initiation of protein synthesis such as 7-methyl-GMP and aurintricarboxylic acid. The nucleotide sequence of this ribosome binding site has been determined: it conatains a GUG codon centered at position 26 that is not in phase with any termination codon within the 5' end nucleotide sequence of the RNA that we have analyzed (101 residues). However, the predicted N-terminal amino acid sequence starting from this GUG codon (or even from any AUG or GUG codon in the 5' end of the RNA) does not coincide with that of the in vitro-synthesized product of the 5' end proximal gag gene. Nevertheless, inhibition of ribosome binding to this site is accompanied by an inhibition of the in vitro translation of the gag gene."}
{"id": "PMID:219250", "title": "Intracellular forms of simian virus 40 nucleoprotein complexes. I. Methods of isolation and characterization in CV-1 cells.", "content": "A new method was developed for isolation of intracellular forms of simian virus 40 (SV40) nucleoprotein complexes from SV40-infected CV-1 cells late in the infectious cycle. In contrast to the Triton extraction method, which yields only a 60-70S complex, this new procedure yielded three forms of SV40 nucleoprotein complexes: complex I, complex II, and the nature virion (V). The three nucleoprotein complexes differed in physical as well as biochemical properties. Complex I, which is only a small portion of the total SV42 nucleoprotein complexes late during infection, was active in synthesizing both SV40-specific DNA and RNA. Pulse-labeling experiments suggest the following metabolic pathway: I leads to II leads to V. Conversion of complex I to II occurred shortly after the completion of SV40 DNA replication and resulted in the inactivation of the biosynthetic activities of I.", "contents": "Intracellular forms of simian virus 40 nucleoprotein complexes. I. Methods of isolation and characterization in CV-1 cells. A new method was developed for isolation of intracellular forms of simian virus 40 (SV40) nucleoprotein complexes from SV40-infected CV-1 cells late in the infectious cycle. In contrast to the Triton extraction method, which yields only a 60-70S complex, this new procedure yielded three forms of SV40 nucleoprotein complexes: complex I, complex II, and the nature virion (V). The three nucleoprotein complexes differed in physical as well as biochemical properties. Complex I, which is only a small portion of the total SV42 nucleoprotein complexes late during infection, was active in synthesizing both SV40-specific DNA and RNA. Pulse-labeling experiments suggest the following metabolic pathway: I leads to II leads to V. Conversion of complex I to II occurred shortly after the completion of SV40 DNA replication and resulted in the inactivation of the biosynthetic activities of I."}
{"id": "PMID:219251", "title": "State and organization of polyoma virus DNA sequences in transformed rat cell lines.", "content": "Polyoma virus-transformed rat cell lines were isolated as colonies growing in agar after infection of F2408 cells with low multiplicities of wild-type virus. Viral DNA present in the transformed cells was analyzed by fractionating the cellular DNA on agarose gels before and after digestion with various restriction endonucleases, followed by detection of the DNA fragments containing viral sequences using the procedure described by Southern (E. Southern, J. Mol. Biol., 98:503--515, 1975). Five lines, independently derived, were studied in detail. All five lines, when examined after a minimum number of passages in culture, contained both free and apparently integrated viral DNA. The free polyoma DNA in three of the lines was indistinguishable, by restriction enzyme analysis, from wild-type viral DNA, whereas the two other lines also contained smaller free DNA molecules which lacked parts of the wild-type genome. The integrated DNA in the five lines studies existed as head-to-tail tandem repeats of unit-length polyoma DNA covalently attached to nonviral DNA. The same five polyoma-transformed rat lines were examined after further passage in culture. Free viral DNA was then either undetectable or greatly reduced in amounts, whereas the high-molecular-weight, integrated units persisted after passage of the cells. The subclones, derived from one of the five lines selected for detailed analysis, showed some variations in the quantity and size of the free viral DNA as well as minor alterations in the pattern of the apparently integrated sequences.", "contents": "State and organization of polyoma virus DNA sequences in transformed rat cell lines. Polyoma virus-transformed rat cell lines were isolated as colonies growing in agar after infection of F2408 cells with low multiplicities of wild-type virus. Viral DNA present in the transformed cells was analyzed by fractionating the cellular DNA on agarose gels before and after digestion with various restriction endonucleases, followed by detection of the DNA fragments containing viral sequences using the procedure described by Southern (E. Southern, J. Mol. Biol., 98:503--515, 1975). Five lines, independently derived, were studied in detail. All five lines, when examined after a minimum number of passages in culture, contained both free and apparently integrated viral DNA. The free polyoma DNA in three of the lines was indistinguishable, by restriction enzyme analysis, from wild-type viral DNA, whereas the two other lines also contained smaller free DNA molecules which lacked parts of the wild-type genome. The integrated DNA in the five lines studies existed as head-to-tail tandem repeats of unit-length polyoma DNA covalently attached to nonviral DNA. The same five polyoma-transformed rat lines were examined after further passage in culture. Free viral DNA was then either undetectable or greatly reduced in amounts, whereas the high-molecular-weight, integrated units persisted after passage of the cells. The subclones, derived from one of the five lines selected for detailed analysis, showed some variations in the quantity and size of the free viral DNA as well as minor alterations in the pattern of the apparently integrated sequences."}
{"id": "PMID:219252", "title": "Feline sarcoma virus-coded polyprotein: enzymatic cleavage by a type C virus-coded structural protein.", "content": "A purified 15,000-molecular-weight (Mr) Prague strain Rous sarcoma virus gag gene-coded structural protein, p15, was shown to enzymatically cleave the previously described 130,000 Mr feline sarcoma virus-coded polyprotein, Pr130. Cleavage products included proteins ranging in molecular weight from 12,000 to 110,000. The specificity of this cleavage reactivity was indicated by the fact that, under similar conditions, neither purified type C viral structural proteins nor nonviral proteins such as bovine serum albumin were cleaved to significant extents. Moreover, feline leukemia virus Pr65gag was efficiently cleaved, resulting in the generations of proteins of 30,000 (p30), 15,000 (p15), 12,000 (p12), and 10,000 (p10) Mr. Using enzymatically (p15) treated feline sarcoma virus Pr130 as starting material, we were able to purify a major 72,000 Mr cleavage product and to show it to contain the previously described feline sarcoma virus-coded nonstructural component.", "contents": "Feline sarcoma virus-coded polyprotein: enzymatic cleavage by a type C virus-coded structural protein. A purified 15,000-molecular-weight (Mr) Prague strain Rous sarcoma virus gag gene-coded structural protein, p15, was shown to enzymatically cleave the previously described 130,000 Mr feline sarcoma virus-coded polyprotein, Pr130. Cleavage products included proteins ranging in molecular weight from 12,000 to 110,000. The specificity of this cleavage reactivity was indicated by the fact that, under similar conditions, neither purified type C viral structural proteins nor nonviral proteins such as bovine serum albumin were cleaved to significant extents. Moreover, feline leukemia virus Pr65gag was efficiently cleaved, resulting in the generations of proteins of 30,000 (p30), 15,000 (p15), 12,000 (p12), and 10,000 (p10) Mr. Using enzymatically (p15) treated feline sarcoma virus Pr130 as starting material, we were able to purify a major 72,000 Mr cleavage product and to show it to contain the previously described feline sarcoma virus-coded nonstructural component."}
{"id": "PMID:219253", "title": "Nucleosomal structure of Epstein-Barr virus DNA in transformed cell lines.", "content": "Micrococcal nuclease digestion was used to analyze Epstein-Barr virus (EBV) DNA structure in nuclei of transformed cells. Digests of virus-producing (P3HR-1), non-virus-producing (Raji), and superinfected Rajii cell nuclei were fractionated by electrophoresis on agarose gels, transferred to nitrocellulose, and hybridized to 32P-labeled EBV DNA. The viral DNA of Raji nuclei produced a series of bands on electrophoresis whose lengths were integral multiples of a unit size, which was the same as the repeat length of host DNA. Viral DNA in nuclei of P3HR-1 and superinfected Raji cells produced faintly visible bands superimposed on a smear of viral DNA which dominated the hybridization pattern. No differences were detected in the patterns when total DNA digests from Raji, P3HR-1, and an EBV DNA-negative cell line (U-698M) were analyzed by ethidium bromide staining or by hybridization with the use of 32P-labeled lymphoblastoid cell DNA as probe. We conclude that the EBV episomal DNA of Raji cells is folded into nucleosomes, whereas most of the viral DNA of P3HR-1 and superinfected Raji cells is not. This pattern of DNA organization differs signficantly from that in papova group viruses.", "contents": "Nucleosomal structure of Epstein-Barr virus DNA in transformed cell lines. Micrococcal nuclease digestion was used to analyze Epstein-Barr virus (EBV) DNA structure in nuclei of transformed cells. Digests of virus-producing (P3HR-1), non-virus-producing (Raji), and superinfected Rajii cell nuclei were fractionated by electrophoresis on agarose gels, transferred to nitrocellulose, and hybridized to 32P-labeled EBV DNA. The viral DNA of Raji nuclei produced a series of bands on electrophoresis whose lengths were integral multiples of a unit size, which was the same as the repeat length of host DNA. Viral DNA in nuclei of P3HR-1 and superinfected Raji cells produced faintly visible bands superimposed on a smear of viral DNA which dominated the hybridization pattern. No differences were detected in the patterns when total DNA digests from Raji, P3HR-1, and an EBV DNA-negative cell line (U-698M) were analyzed by ethidium bromide staining or by hybridization with the use of 32P-labeled lymphoblastoid cell DNA as probe. We conclude that the EBV episomal DNA of Raji cells is folded into nucleosomes, whereas most of the viral DNA of P3HR-1 and superinfected Raji cells is not. This pattern of DNA organization differs signficantly from that in papova group viruses."}
{"id": "PMID:219254", "title": "Molecular genetics of herpes simplex virus. II. Mapping of the major viral glycoproteins and of the genetic loci specifying the social behavior of infected cells.", "content": "We have mapped the location in herpes simplex virus (HSV) DNA of (i) three mutations at different loci (syn loci) which alter the social behavior of infected cells from clumping of rounded cells to polykaryocytosis, (ii) a mutation which determines the accumulation of one major glycoprotein [VP8.0(C(2))], and (iii) the sequences encoding four major virus glycoproteins [VP8.0(C(2)), VP7(B(2)), VP8.5(A), and VP19E(D(2))]. The experimental design and results were as follows. (i) Analysis of HSV-1 x HSV-2 recombinants showed that the sequences encoding the VP19E(D(2)) glycoprotein map in the S component, whereas the sequences encoding the other three major glycoproteins are in two locations in the L component of HSV DNA. The templates specifying the HSV-1 and HSV-2 glycoprotein VP8.0(C(2)) appear not to be colinear; we isolated recombinants specifying glycoproteins comigrating in sodium dodecyl sulfate-polyacrylamide gels with VP8.0(C(2)) of both HSV-1 and HSV-2. (ii) Marker rescue of a ts mutant defective in accumulation of glycoprotein VP7(B(2)) showed that the mutation maps within a region containing the sequences encoding that glycoprotein. (iii) Marker transfer experiments involving transfection of rabbit skin cells with donor HSV-1(F) DNA and fragments from several donor strains causing fusion of Vero or both Vero and HEp-2 cells revealed the existence of three syn loci specifying the social behavior of cells and one locus (Cr) determining the accumulation of glycoprotein VP8.0(C(2)). The Cr locus maps to the right of the template specifying VP8.0(C(2)) glycoprotein. Loci syn 1 and syn 2 map at or near the Cr locus but can be segregated from it. Locus syn 3 maps at or near the template specifying glycoproteins VP7(B(2)) and VP8.5(A). The expression of mutations in the syn 1 and syn 3 loci appear to be cell type dependent, in that recombinants with these mutations fuse Vero cells but not HEp-2 cells. Recipients of the syn 2 locus or of both syn 2 and syn 1 loci fuse both Vero and HEp-2 cells.", "contents": "Molecular genetics of herpes simplex virus. II. Mapping of the major viral glycoproteins and of the genetic loci specifying the social behavior of infected cells. We have mapped the location in herpes simplex virus (HSV) DNA of (i) three mutations at different loci (syn loci) which alter the social behavior of infected cells from clumping of rounded cells to polykaryocytosis, (ii) a mutation which determines the accumulation of one major glycoprotein [VP8.0(C(2))], and (iii) the sequences encoding four major virus glycoproteins [VP8.0(C(2)), VP7(B(2)), VP8.5(A), and VP19E(D(2))]. The experimental design and results were as follows. (i) Analysis of HSV-1 x HSV-2 recombinants showed that the sequences encoding the VP19E(D(2)) glycoprotein map in the S component, whereas the sequences encoding the other three major glycoproteins are in two locations in the L component of HSV DNA. The templates specifying the HSV-1 and HSV-2 glycoprotein VP8.0(C(2)) appear not to be colinear; we isolated recombinants specifying glycoproteins comigrating in sodium dodecyl sulfate-polyacrylamide gels with VP8.0(C(2)) of both HSV-1 and HSV-2. (ii) Marker rescue of a ts mutant defective in accumulation of glycoprotein VP7(B(2)) showed that the mutation maps within a region containing the sequences encoding that glycoprotein. (iii) Marker transfer experiments involving transfection of rabbit skin cells with donor HSV-1(F) DNA and fragments from several donor strains causing fusion of Vero or both Vero and HEp-2 cells revealed the existence of three syn loci specifying the social behavior of cells and one locus (Cr) determining the accumulation of glycoprotein VP8.0(C(2)). The Cr locus maps to the right of the template specifying VP8.0(C(2)) glycoprotein. Loci syn 1 and syn 2 map at or near the Cr locus but can be segregated from it. Locus syn 3 maps at or near the template specifying glycoproteins VP7(B(2)) and VP8.5(A). The expression of mutations in the syn 1 and syn 3 loci appear to be cell type dependent, in that recombinants with these mutations fuse Vero cells but not HEp-2 cells. Recipients of the syn 2 locus or of both syn 2 and syn 1 loci fuse both Vero and HEp-2 cells."}
{"id": "PMID:219255", "title": "Molecular genetics of herpes simplex virus. III. Fine mapping of a genetic locus determining resistance to phosphonoacetate by two methods of marker transfer.", "content": "We have transferred a genetic locus determining resistance to phosphonoacetic acid (PAAr) from one herpes simplex viral genome to another by two methods of marker transfer. One method requires recombination between an intact DNA molecule and a restriction endonuclease DNA fragment, whereas the other requires repair of a partial heteroduplex formed between the two DNA molecules. These two methods mapped the PAAr locus between positions 0.45 and 0.53 map units on the physical map of the viral DNA. Fine mapping of the PAAr locus showed that it maps at or near an EcoRI restriction endonuclease site at either 0.46 or 0.49 map units. We also describe and compare the two methods of marker transfer.", "contents": "Molecular genetics of herpes simplex virus. III. Fine mapping of a genetic locus determining resistance to phosphonoacetate by two methods of marker transfer. We have transferred a genetic locus determining resistance to phosphonoacetic acid (PAAr) from one herpes simplex viral genome to another by two methods of marker transfer. One method requires recombination between an intact DNA molecule and a restriction endonuclease DNA fragment, whereas the other requires repair of a partial heteroduplex formed between the two DNA molecules. These two methods mapped the PAAr locus between positions 0.45 and 0.53 map units on the physical map of the viral DNA. Fine mapping of the PAAr locus showed that it maps at or near an EcoRI restriction endonuclease site at either 0.46 or 0.49 map units. We also describe and compare the two methods of marker transfer."}
{"id": "PMID:219256", "title": "Phosphorylation of T-antigen and control T-antigen expression in cells transformed by wild-type and tsA mutants of simian virus 40.", "content": "Chinese hamster lung (CHL) cells transformed by wild-type simian virus 40 (cell line CHLWT15) or transformed by the simian virus 40 mutants tsA30 (cell lines CHLA30L1 and CHLA30L2) or tsA239 (cell line CHLA239L1) were used to determine the rates of turnover and synthesis of the T-antigen protein and the rate of turnover of the phosphate group(s) attached to the T-antigen at both the permissive and restrictive temperatures. The phosphate group turned over several times within the lifetime of the protein to which it was attached, with the exception of the phosphate group in the tsA transformants at 40 degrees C, which turned over at the same rate as the T-antigen protein. The steady-state levels of the T-antigens (molecular weights, 92,000 [92K] and 17K) and the amount of simian virus 40-specific RNA was also determined in each of the lines. The CHLA30L1 line contained two to three times more early simian virus 40 RNA than the CHLA30L2 line; although neither line formed colonies in agar at 40 degrees C, CHLA30L1 overgrew a normal monolayer at 40 degrees C. The rate of 92K-T-antigen synthesis was 1.5 times faster in CHLA30L1 than in CHLA30L2 at 33 degrees C and 4 times faster at 40 degrees C. The different phenotype of these two presumably isogenic cell lines seem to be related to the levels of the T-antigens. The ratios of the 92K T-antigen to the 17K T-antigens were similar in the two lines. Transformed CHL cell lines, unlike transformed mouse 3T3 cell lines, were found to contain very small amounts of the 56K T-antigen.", "contents": "Phosphorylation of T-antigen and control T-antigen expression in cells transformed by wild-type and tsA mutants of simian virus 40. Chinese hamster lung (CHL) cells transformed by wild-type simian virus 40 (cell line CHLWT15) or transformed by the simian virus 40 mutants tsA30 (cell lines CHLA30L1 and CHLA30L2) or tsA239 (cell line CHLA239L1) were used to determine the rates of turnover and synthesis of the T-antigen protein and the rate of turnover of the phosphate group(s) attached to the T-antigen at both the permissive and restrictive temperatures. The phosphate group turned over several times within the lifetime of the protein to which it was attached, with the exception of the phosphate group in the tsA transformants at 40 degrees C, which turned over at the same rate as the T-antigen protein. The steady-state levels of the T-antigens (molecular weights, 92,000 [92K] and 17K) and the amount of simian virus 40-specific RNA was also determined in each of the lines. The CHLA30L1 line contained two to three times more early simian virus 40 RNA than the CHLA30L2 line; although neither line formed colonies in agar at 40 degrees C, CHLA30L1 overgrew a normal monolayer at 40 degrees C. The rate of 92K-T-antigen synthesis was 1.5 times faster in CHLA30L1 than in CHLA30L2 at 33 degrees C and 4 times faster at 40 degrees C. The different phenotype of these two presumably isogenic cell lines seem to be related to the levels of the T-antigens. The ratios of the 92K T-antigen to the 17K T-antigens were similar in the two lines. Transformed CHL cell lines, unlike transformed mouse 3T3 cell lines, were found to contain very small amounts of the 56K T-antigen."}
{"id": "PMID:219257", "title": "Transformation of human embryonic kidney cells by human papovarirus BK.", "content": "Infection of secondary human embryonic kidney (HEK) cells with human papovavirus BK (BKV) resulted in cellular lysis and degeneration within 7 days. After 30 days, multilayered colonies of transformed cells were found and subcultured for analyses. These BK-HEK cells uniformly expressed the BKV T-antigen but were only 1% V-antigen positive. They produced infectious virus and were resistant to superinfection by BKV. They reached a saturation density of 1.3 x 10(5) cells per cm2 in medium with 5% fetal calf serum, were able to grow in medium containing 2% serum, and did not form colonies in soft agar or tumors in nude mice. Nonintegrated, superhelical BKV DNA was detected in the noncloned cells as expected because they were persistently infected and contained RNA transcripts complementary to both early and late regions of the BKV genome. Analysis of T-antigen-positive clonal isolates of these BK-HEK cells by the Southern technique revealed an absence of free viral DNA and the presencce of integrated BKV DNA sequences corresponding to the early region of the BKV genome. These studies demonstrate the stable transformation of human cells by BKV. However, the transformed human cells which retain and express part of the BKV genome do not fully manifest the growth properties of other papovarirus-transformed cells.", "contents": "Transformation of human embryonic kidney cells by human papovarirus BK. Infection of secondary human embryonic kidney (HEK) cells with human papovavirus BK (BKV) resulted in cellular lysis and degeneration within 7 days. After 30 days, multilayered colonies of transformed cells were found and subcultured for analyses. These BK-HEK cells uniformly expressed the BKV T-antigen but were only 1% V-antigen positive. They produced infectious virus and were resistant to superinfection by BKV. They reached a saturation density of 1.3 x 10(5) cells per cm2 in medium with 5% fetal calf serum, were able to grow in medium containing 2% serum, and did not form colonies in soft agar or tumors in nude mice. Nonintegrated, superhelical BKV DNA was detected in the noncloned cells as expected because they were persistently infected and contained RNA transcripts complementary to both early and late regions of the BKV genome. Analysis of T-antigen-positive clonal isolates of these BK-HEK cells by the Southern technique revealed an absence of free viral DNA and the presencce of integrated BKV DNA sequences corresponding to the early region of the BKV genome. These studies demonstrate the stable transformation of human cells by BKV. However, the transformed human cells which retain and express part of the BKV genome do not fully manifest the growth properties of other papovarirus-transformed cells."}
{"id": "PMID:219258", "title": "Structural analysis of the avian sarcoma virus transforming protein: sites of phosphorylation.", "content": "The avian sarcoma virus (ASV) protein responsible for cellular transformation in vitro and sarcomagenesis in animals was studied structurally with special reference to the sites of phosphorylation on the polypeptide. The product of the ASV src gene, pp60src, is a phosphoprotein of 60,000 daltons. We found that pp60src contained two major sites of phosphorylation, one involving phosphoserine and the other involving phosphothreonine and possible addtional minor sites of phosphorylation. By using N-formyl[35S]methionyl-tRNAf as a radiolabeled precursor in the cell-free synthesis of the src protein in conjunction with partial proteolysis mapping, we determined that the major phosphoserine residue was located on the amino-terminal two-thirds of the molecule and that the phosphothreonine was located on the carboxy-terminal third. We further determined that the phosphorylation of pp60src in cell extracts involved at least two protein kinases, the one that phosphorylated the major serine site being cyclic AMP dependent and the other, acting on the threonine residue, being a cyclic nucleotide-independnet phosphotransferase. Finally, analysis of the pp60src isolated from cells infected with a temperature-sensitive src gene mutant of ASV revealed that phosphorylation of the major threonine residue was severely reduced when infected cells were grown at the nonpermissive temperature, whereas a phosphorylation pattern characteristic of the wild-type pp60src was observed at the permissive temperature. As pp60src has an associated protein kinase activity, the possible involvement of phosphorylation-dephosphorylation reactions in the functional regulation of ASV transforming protein enzymatic activity is discussed.", "contents": "Structural analysis of the avian sarcoma virus transforming protein: sites of phosphorylation. The avian sarcoma virus (ASV) protein responsible for cellular transformation in vitro and sarcomagenesis in animals was studied structurally with special reference to the sites of phosphorylation on the polypeptide. The product of the ASV src gene, pp60src, is a phosphoprotein of 60,000 daltons. We found that pp60src contained two major sites of phosphorylation, one involving phosphoserine and the other involving phosphothreonine and possible addtional minor sites of phosphorylation. By using N-formyl[35S]methionyl-tRNAf as a radiolabeled precursor in the cell-free synthesis of the src protein in conjunction with partial proteolysis mapping, we determined that the major phosphoserine residue was located on the amino-terminal two-thirds of the molecule and that the phosphothreonine was located on the carboxy-terminal third. We further determined that the phosphorylation of pp60src in cell extracts involved at least two protein kinases, the one that phosphorylated the major serine site being cyclic AMP dependent and the other, acting on the threonine residue, being a cyclic nucleotide-independnet phosphotransferase. Finally, analysis of the pp60src isolated from cells infected with a temperature-sensitive src gene mutant of ASV revealed that phosphorylation of the major threonine residue was severely reduced when infected cells were grown at the nonpermissive temperature, whereas a phosphorylation pattern characteristic of the wild-type pp60src was observed at the permissive temperature. As pp60src has an associated protein kinase activity, the possible involvement of phosphorylation-dephosphorylation reactions in the functional regulation of ASV transforming protein enzymatic activity is discussed."}
{"id": "PMID:219259", "title": "Nucleotide sequence analysis of two simian virus 40 mutants with deletions in the late region of the genome.", "content": "Two mutants of simian virus 40, dl-1261 and dl-1262, have deletions that map between coordinated 0.90 and 0.95 (Cole et al., J. Virol 24:277--294, 1977). Both affect the structure of the two minor proteins VP2 and VP3. The precise location and size of the deletions have now been determined by nucleotide sequence analysis. Mutant dl-1261 is deleted of 54 base pairs, is temperature sensitive for the protein defined by the D complementation group, and promotes the synthesis of shorter VP2 and VP3 polypeptides. Mutant dl-1262 is viable irrespective of temperature and has a deletion of 36 base pairs, 23 of which overlap the deletion in dl-1261. Since these mutants produce normal VP1, the deleted regions probably have no function in the splicing of precursor RNA to the VP1 mRNA.", "contents": "Nucleotide sequence analysis of two simian virus 40 mutants with deletions in the late region of the genome. Two mutants of simian virus 40, dl-1261 and dl-1262, have deletions that map between coordinated 0.90 and 0.95 (Cole et al., J. Virol 24:277--294, 1977). Both affect the structure of the two minor proteins VP2 and VP3. The precise location and size of the deletions have now been determined by nucleotide sequence analysis. Mutant dl-1261 is deleted of 54 base pairs, is temperature sensitive for the protein defined by the D complementation group, and promotes the synthesis of shorter VP2 and VP3 polypeptides. Mutant dl-1262 is viable irrespective of temperature and has a deletion of 36 base pairs, 23 of which overlap the deletion in dl-1261. Since these mutants produce normal VP1, the deleted regions probably have no function in the splicing of precursor RNA to the VP1 mRNA."}
{"id": "PMID:219260", "title": "Monomer and multimer covalently closed circular forms of Rous sarcoma virus DNA.", "content": "Covalently closed circular molecules of viral DNA synthesized in virus-infected cells are composed mainly of monomers sedimenting at 22 to 27S in neutral sucrose gradients. These monomers are detected by annealing with complementary DNA or transfection assay. However, 11% of the infectious circles sediment faster than monomers. There is a peak at 32S which may correspond to dimer molecules. Traces of infectivity (about 3%) found between 32S and 65S suggest the presence of higher oligomers. In alkaline sucrose gradients, covalently closed monomers are found at 64 to 71S. Infectivity of these monomers is reduced by alkali treatment to less than one-tenth, and, perhaps for this reason, no infectious dimers or higher oligomers are observed. It has been shown that upon resedimentation the dimers of 95 can be separated from monomers and detected by hybridization.", "contents": "Monomer and multimer covalently closed circular forms of Rous sarcoma virus DNA. Covalently closed circular molecules of viral DNA synthesized in virus-infected cells are composed mainly of monomers sedimenting at 22 to 27S in neutral sucrose gradients. These monomers are detected by annealing with complementary DNA or transfection assay. However, 11% of the infectious circles sediment faster than monomers. There is a peak at 32S which may correspond to dimer molecules. Traces of infectivity (about 3%) found between 32S and 65S suggest the presence of higher oligomers. In alkaline sucrose gradients, covalently closed monomers are found at 64 to 71S. Infectivity of these monomers is reduced by alkali treatment to less than one-tenth, and, perhaps for this reason, no infectious dimers or higher oligomers are observed. It has been shown that upon resedimentation the dimers of 95 can be separated from monomers and detected by hybridization."}
{"id": "PMID:219261", "title": "Size of the intracellular circular Epstein-Barr virus DNA molecules in infectious mononucleosis-derived human lymphoid cell lines.", "content": "The size of non-integrated circular Epstein-Barr virus (EBV) DNA molecules isolated from seven different human lymphoblastoid cell lines of infectious mononucleosis origin has been determined by sedimentation analysis and by direct contour length measurements on electron micrographs. Six lines had intracellular circular EBV genomes of the same size as linear virion DNA molecules. The seventh line, established with the B95-8 strain of EBV, was the only one found to have circular EBV DNA molecules significantly smaller than virion DNA. The data show that intracellular EBV DNA circles of reduced size do not generally occur in infectious mononucleosis-derived cell lines.", "contents": "Size of the intracellular circular Epstein-Barr virus DNA molecules in infectious mononucleosis-derived human lymphoid cell lines. The size of non-integrated circular Epstein-Barr virus (EBV) DNA molecules isolated from seven different human lymphoblastoid cell lines of infectious mononucleosis origin has been determined by sedimentation analysis and by direct contour length measurements on electron micrographs. Six lines had intracellular circular EBV genomes of the same size as linear virion DNA molecules. The seventh line, established with the B95-8 strain of EBV, was the only one found to have circular EBV DNA molecules significantly smaller than virion DNA. The data show that intracellular EBV DNA circles of reduced size do not generally occur in infectious mononucleosis-derived cell lines."}
{"id": "PMID:219262", "title": "Anatomy of herpes simplex virus DNA. XI. Apparent clustering of functions effecting rapid inhibition of host DNA and protein synthesis.", "content": "Herpes simplex virus type 2 (HSV-2) strains inhibit the synthesis of both DNA and protein of the host cell more rapidly than HSV-1 strains. Several intertypic HSV-1 X HSV-2 recombinants and parental strains were examined for their ability to inhibit rapidly the synthesis of host protein and DNA. The two functions cosegregated in all of eight recombinants tested and are therefore controlled by the same gene or by different genes in the same region of the viral DNA.", "contents": "Anatomy of herpes simplex virus DNA. XI. Apparent clustering of functions effecting rapid inhibition of host DNA and protein synthesis. Herpes simplex virus type 2 (HSV-2) strains inhibit the synthesis of both DNA and protein of the host cell more rapidly than HSV-1 strains. Several intertypic HSV-1 X HSV-2 recombinants and parental strains were examined for their ability to inhibit rapidly the synthesis of host protein and DNA. The two functions cosegregated in all of eight recombinants tested and are therefore controlled by the same gene or by different genes in the same region of the viral DNA."}
{"id": "PMID:219263", "title": "Prostatic adenocarcinoma of ductal origin.", "content": "Adenocarcinomas that arise from primary or secondary prostatic ducts have distinctive histopathologic features. The age of patients, symptoms, findings on digital rectal examination and determinations of serum acid and alkaline phosphatase are similar to those of patients with acinic carcinomas. Carcinomas of secondary ducts may be less responsive to endocrine manipulation and of greater malignancy than carcinomas of primary ducts. The course and survival of patients with ductal carcinomas treated conservatively are poor.", "contents": "Prostatic adenocarcinoma of ductal origin. Adenocarcinomas that arise from primary or secondary prostatic ducts have distinctive histopathologic features. The age of patients, symptoms, findings on digital rectal examination and determinations of serum acid and alkaline phosphatase are similar to those of patients with acinic carcinomas. Carcinomas of secondary ducts may be less responsive to endocrine manipulation and of greater malignancy than carcinomas of primary ducts. The course and survival of patients with ductal carcinomas treated conservatively are poor."}
{"id": "PMID:219264", "title": "Case report: cystic partially differentiated nephroblastoma (Wilms tumor).", "content": "A case of a cystic partially differentiated nephroblastoma treated with combined chemotherapy after removal in a 2-month old newborn is reported. Cystic partially differentiated nephroblastoma is a newly described clinicopathologic entity, involving elements of a nephroblastoma and cystic disease, and it is believed to be a pathologic derivative of the metanephric blastema and not related to renal dysplasia. Cystic partially differentiated nephroblastoma is distinguished from multilocular cysts of the kidney by the presence of partially differentiated renal elements in the septa of cysts. The aggressive appearance of the cells led to the treatment of this tumor as potentially malignant.", "contents": "Case report: cystic partially differentiated nephroblastoma (Wilms tumor). A case of a cystic partially differentiated nephroblastoma treated with combined chemotherapy after removal in a 2-month old newborn is reported. Cystic partially differentiated nephroblastoma is a newly described clinicopathologic entity, involving elements of a nephroblastoma and cystic disease, and it is believed to be a pathologic derivative of the metanephric blastema and not related to renal dysplasia. Cystic partially differentiated nephroblastoma is distinguished from multilocular cysts of the kidney by the presence of partially differentiated renal elements in the septa of cysts. The aggressive appearance of the cells led to the treatment of this tumor as potentially malignant."}
{"id": "PMID:219265", "title": "Wilms tumor in adolescence.", "content": "A review of the literature reveals that Wilms tumor is rare in adolescence. At the time of diagnosis 78 per cent of children are less than 5 years old. Of 17 cases of Wilms tumor seen at the Ontario Cancer Foundation Clinic in Kingston from 1973 to 1975, 3 children were between 16 and 17 years old. Of 316 cases registered in Ontario with the Ontario Cancer Treatment and Research Foundation only 5 were in the 15 to 19-year age group. The possibility of Wilms tumor in patients beyond the usual age group is not considered as a differential diagnosis because of its relative rarity. Patients may present with features suggestive of neuroblastoma, renal cell carcinoma, hydronephrosis, cholecystitis, appendicitis and twisted ovarian cyst as seen in our 3 patients. In comparison, a review of 84 reported cases of renal cell carcinoma in children from 1934 to 1974 showed 5 cases in the 15 to 18-year age group.", "contents": "Wilms tumor in adolescence. A review of the literature reveals that Wilms tumor is rare in adolescence. At the time of diagnosis 78 per cent of children are less than 5 years old. Of 17 cases of Wilms tumor seen at the Ontario Cancer Foundation Clinic in Kingston from 1973 to 1975, 3 children were between 16 and 17 years old. Of 316 cases registered in Ontario with the Ontario Cancer Treatment and Research Foundation only 5 were in the 15 to 19-year age group. The possibility of Wilms tumor in patients beyond the usual age group is not considered as a differential diagnosis because of its relative rarity. Patients may present with features suggestive of neuroblastoma, renal cell carcinoma, hydronephrosis, cholecystitis, appendicitis and twisted ovarian cyst as seen in our 3 patients. In comparison, a review of 84 reported cases of renal cell carcinoma in children from 1934 to 1974 showed 5 cases in the 15 to 18-year age group."}
{"id": "PMID:219266", "title": "Stress-induced cortisol release in hypothalamic hypoadrenalism.", "content": "A 52-year-old woman experienced hypoadrenalism (mean 8 AM plasma cortisol level, 3.7 microgram/dL) after hypothalamic surgery and radiotherapy for craniopharyngioma. Despite low plasma adrenocorticotropic hormone levels (less than 25 pg/mL), absent diurnal variation of the plasma cortisol level, and subnormal urinary 17-hydroxycorticosteroid response to metyrapone, she had normal plasma cortisol responses to insulin-induced hypoglycemia and to administration of vasopressin or synthetic adrenocorticotropic hormone. Stress-induced cortical release may be preserved despite notable abnormalities in regulation of cortisol secretion by diurnal and feedback-mediated mechanisms.", "contents": "Stress-induced cortisol release in hypothalamic hypoadrenalism. A 52-year-old woman experienced hypoadrenalism (mean 8 AM plasma cortisol level, 3.7 microgram/dL) after hypothalamic surgery and radiotherapy for craniopharyngioma. Despite low plasma adrenocorticotropic hormone levels (less than 25 pg/mL), absent diurnal variation of the plasma cortisol level, and subnormal urinary 17-hydroxycorticosteroid response to metyrapone, she had normal plasma cortisol responses to insulin-induced hypoglycemia and to administration of vasopressin or synthetic adrenocorticotropic hormone. Stress-induced cortical release may be preserved despite notable abnormalities in regulation of cortisol secretion by diurnal and feedback-mediated mechanisms."}
{"id": "PMID:219267", "title": "Thymosin fraction V and intensive combination chemotherapy. Prolonging the survival of patients with small-cell lung cancer.", "content": "Patients with small-cell bronchogenic carcinoma who received intensive remission-induction chemotherapy randomly received either thymosin fraction V, 60 mg/sq m or 20 mg/sq m twice weekly, or no thymosin treatment during the initial six weeks of chemotherapy. Chemotherapy was then continued for two years. Thymosin administration did not increase the complete response rate. Patients receiving thymosin, 60 mg/sq m, had significantly prolonged survival times relative to the other treatment groups. This benefit was due to prolonged relapse-free survival in complete responders to treatment. The mechanism by which thymosin increased survival duration is unclear but may relate to restoration of immune deficits due to disease or treatment.", "contents": "Thymosin fraction V and intensive combination chemotherapy. Prolonging the survival of patients with small-cell lung cancer. Patients with small-cell bronchogenic carcinoma who received intensive remission-induction chemotherapy randomly received either thymosin fraction V, 60 mg/sq m or 20 mg/sq m twice weekly, or no thymosin treatment during the initial six weeks of chemotherapy. Chemotherapy was then continued for two years. Thymosin administration did not increase the complete response rate. Patients receiving thymosin, 60 mg/sq m, had significantly prolonged survival times relative to the other treatment groups. This benefit was due to prolonged relapse-free survival in complete responders to treatment. The mechanism by which thymosin increased survival duration is unclear but may relate to restoration of immune deficits due to disease or treatment."}
{"id": "PMID:219269", "title": "Dianhydrogalactitol and radiation therapy. Treatment of supratentorial glioma.", "content": "Dianhydrogalactitol was the most active of 177 agents tested against a mouse ependymoblastoma tumor. We conducted a prospectively randomized trial comparing whole-brain irradiation alone vs identical irradiation plus dianhydrogalactitol in 42 patients with grade 3 and 4 supratentorial astrocytomas. Patients receiving dianhydrogalactitol in addition to irradiation had a significantly longer median survival time (67 vs 35 weeks) than did patients receiving only irradiation. The major toxic effect of dianhydrogalactitol is hematologic suppression of a cumulative nature. Dianhydrogalactitol may play an important role (in conjunction with radiation therapy) in the initial treatment of patients with supratentorial glioma. Our data may indicate that the mouse ependymoblastoma system is a useful screen for agents to be used in the treatment of human glioma.", "contents": "Dianhydrogalactitol and radiation therapy. Treatment of supratentorial glioma. Dianhydrogalactitol was the most active of 177 agents tested against a mouse ependymoblastoma tumor. We conducted a prospectively randomized trial comparing whole-brain irradiation alone vs identical irradiation plus dianhydrogalactitol in 42 patients with grade 3 and 4 supratentorial astrocytomas. Patients receiving dianhydrogalactitol in addition to irradiation had a significantly longer median survival time (67 vs 35 weeks) than did patients receiving only irradiation. The major toxic effect of dianhydrogalactitol is hematologic suppression of a cumulative nature. Dianhydrogalactitol may play an important role (in conjunction with radiation therapy) in the initial treatment of patients with supratentorial glioma. Our data may indicate that the mouse ependymoblastoma system is a useful screen for agents to be used in the treatment of human glioma."}
{"id": "PMID:219274", "title": "Reactivation of herpes simplex virus (type 2) infection in trigeminal ganglia and oral lips with cyclophosphamide treatment.", "content": "Age-dependent resistance in trigeminal nerve against type 2 herpes simplex virus infection through oral lips and reactivation of the latent virus infection with cyclophosphamide in the ganglion in correlation to theprimary infected part were studied in mice with immunofluorescent and histopathological methods. The mice acquired resistance in the nervous tissue after 8 weeks of age. The viral antigen appeared in all trigeminal ganglia immediately after infection, but not found at 4 weeks later. Reactivation of the latent infection was tried by using 8-week-old mice with cyclophosphamide treatment. Four to five times administration of the drug produced the leasions of herpes simplex virus infection in the ganglia and also in the primary infected areas, but viral antigen-bearing neurons in the ganglia were very few.", "contents": "Reactivation of herpes simplex virus (type 2) infection in trigeminal ganglia and oral lips with cyclophosphamide treatment. Age-dependent resistance in trigeminal nerve against type 2 herpes simplex virus infection through oral lips and reactivation of the latent virus infection with cyclophosphamide in the ganglion in correlation to theprimary infected part were studied in mice with immunofluorescent and histopathological methods. The mice acquired resistance in the nervous tissue after 8 weeks of age. The viral antigen appeared in all trigeminal ganglia immediately after infection, but not found at 4 weeks later. Reactivation of the latent infection was tried by using 8-week-old mice with cyclophosphamide treatment. Four to five times administration of the drug produced the leasions of herpes simplex virus infection in the ganglia and also in the primary infected areas, but viral antigen-bearing neurons in the ganglia were very few."}
{"id": "PMID:219275", "title": "Vertical transmission of type 2 herpes simplex virus infection in immunosuppressed hamsters.", "content": "The effect of immunosuppressive procedure with cyclophosphamide on the vertical transmission of the type 2 herpes simplex virus in hamsters was investigated. Single injection of the cyclophoshamide one day before virus inoculation in various stages of pregnant course caused high rate of placental and fetal infection of the virus. Immunofluorescence technique revealed the presence of viral antigen in more than 90% of placentas and 29% of fetuses with treatment at the middle of late stage of gestation. The drug treatment alone without viral infection brought no detectable changes in placentas or fetuses, whereas slight depletion of mononuclear cells in perifollicular area of the spleen was found. The drug could destroy easily the defense mechanism of the placenta.", "contents": "Vertical transmission of type 2 herpes simplex virus infection in immunosuppressed hamsters. The effect of immunosuppressive procedure with cyclophosphamide on the vertical transmission of the type 2 herpes simplex virus in hamsters was investigated. Single injection of the cyclophoshamide one day before virus inoculation in various stages of pregnant course caused high rate of placental and fetal infection of the virus. Immunofluorescence technique revealed the presence of viral antigen in more than 90% of placentas and 29% of fetuses with treatment at the middle of late stage of gestation. The drug treatment alone without viral infection brought no detectable changes in placentas or fetuses, whereas slight depletion of mononuclear cells in perifollicular area of the spleen was found. The drug could destroy easily the defense mechanism of the placenta."}
{"id": "PMID:219276", "title": "The resistance of G mouse fibroblasts to murine leukemia virus infection.", "content": "In vitro resistance of G mouse cells was not expressed in the initial cycle of MuLV infection but in the propagation of virus to the surrounding cells.", "contents": "The resistance of G mouse fibroblasts to murine leukemia virus infection. In vitro resistance of G mouse cells was not expressed in the initial cycle of MuLV infection but in the propagation of virus to the surrounding cells."}
{"id": "PMID:219282", "title": "Morphologic and biochemical characteristics of transplantable neurogenic tumors induced by N-ethyl-N-nitrosourea in inbred BD IX rats.", "content": "Brain and nerve tumors were induced transplacentally in inbred BD IX rats by systemic application of N-ethyl-N-nitrosourea. Because primary gliomas and neurinomas produced in this way are composed of heterogeneous cell populations, changes in tumor morphology were expected to occur during serial transplantation in syngeneic hosts. In this study such changes in morphology were correlated with the expression of two biochemical nervous system markers, S-100 protein and 2',3'-cyclic nucleotide 3'-phosphohydrolase. Several changes were observed during serial transplantation, including increased growth rate (even after one passage), preferential growth of anaplastic versus differentiated glial and Schwann's cells, varying degrees of fibrosarcomatous changes after prolonged serial transplantation, and reduced levels of S-100 protein. In contrast, tumors derived from biochemically differentiated clonal cell lines retained their morphologic and biochemical characteristics to a much greater extent, even after prolonged periods of sc transplantation.", "contents": "Morphologic and biochemical characteristics of transplantable neurogenic tumors induced by N-ethyl-N-nitrosourea in inbred BD IX rats. Brain and nerve tumors were induced transplacentally in inbred BD IX rats by systemic application of N-ethyl-N-nitrosourea. Because primary gliomas and neurinomas produced in this way are composed of heterogeneous cell populations, changes in tumor morphology were expected to occur during serial transplantation in syngeneic hosts. In this study such changes in morphology were correlated with the expression of two biochemical nervous system markers, S-100 protein and 2',3'-cyclic nucleotide 3'-phosphohydrolase. Several changes were observed during serial transplantation, including increased growth rate (even after one passage), preferential growth of anaplastic versus differentiated glial and Schwann's cells, varying degrees of fibrosarcomatous changes after prolonged serial transplantation, and reduced levels of S-100 protein. In contrast, tumors derived from biochemically differentiated clonal cell lines retained their morphologic and biochemical characteristics to a much greater extent, even after prolonged periods of sc transplantation."}
{"id": "PMID:219283", "title": "Autogenous antibodies against the murine mammary tumor virus in strains of mice with low incidences of mammary tumors.", "content": "The radioimmunoprecipitation assay for the murine mammary tumor virus (MuMTV) was used to detect naturally occurring antibodies against MuMTV in 3 groups of highly inbred mouse strains. 1) Some strains had high incidences of mammary tumors, such as strains GR and C3H. Antibodies against MuMTV were detected in the sera of females of these strains at early ages. 2) Some mouse strains had low incidences of mammary tumors with an intermediate MuMTV expression, such as strains C3Hf, RIIIf, and BALB/c. Some females of these strains developed antibodies against MuMTV. Hormone treatment of these mice resulted in an increase in the proportion of mice carrying antibodies against MuMTV. 3) Some mouse strains were MuMTV-free, such as strains O20, C57BL, and Gr-Mtv2-. No antibodies against MuMTV were detected in the sera of these mice. However, antibodies against MuMTV appeared in the sera of these animals after hormone treatment. The presence of a natural humoral immunity toward MuMTV appeared to be related to the expression of MuMTV in the animals.", "contents": "Autogenous antibodies against the murine mammary tumor virus in strains of mice with low incidences of mammary tumors. The radioimmunoprecipitation assay for the murine mammary tumor virus (MuMTV) was used to detect naturally occurring antibodies against MuMTV in 3 groups of highly inbred mouse strains. 1) Some strains had high incidences of mammary tumors, such as strains GR and C3H. Antibodies against MuMTV were detected in the sera of females of these strains at early ages. 2) Some mouse strains had low incidences of mammary tumors with an intermediate MuMTV expression, such as strains C3Hf, RIIIf, and BALB/c. Some females of these strains developed antibodies against MuMTV. Hormone treatment of these mice resulted in an increase in the proportion of mice carrying antibodies against MuMTV. 3) Some mouse strains were MuMTV-free, such as strains O20, C57BL, and Gr-Mtv2-. No antibodies against MuMTV were detected in the sera of these mice. However, antibodies against MuMTV appeared in the sera of these animals after hormone treatment. The presence of a natural humoral immunity toward MuMTV appeared to be related to the expression of MuMTV in the animals."}
{"id": "PMID:219284", "title": "Prevention of spontaneous leukemia in AKR mice by passive immunization and type specificity of this protection.", "content": "AKR mice were given sc injections of goat antiviral immune globulin from birth through 14 or 31 days of age. Although the shorter immunization schedule greatly reduced expression of spontaneous leukemia, the longer immunization period was required for essentially complete prevention of leukemia. Immune globulin with a high neutralization titer for ecotropic virus provided this protection, whereas antibody with a high neutralization titer for murine xenotropic virus did not.", "contents": "Prevention of spontaneous leukemia in AKR mice by passive immunization and type specificity of this protection. AKR mice were given sc injections of goat antiviral immune globulin from birth through 14 or 31 days of age. Although the shorter immunization schedule greatly reduced expression of spontaneous leukemia, the longer immunization period was required for essentially complete prevention of leukemia. Immune globulin with a high neutralization titer for ecotropic virus provided this protection, whereas antibody with a high neutralization titer for murine xenotropic virus did not."}
{"id": "PMID:219286", "title": "[Role of the kinin and sympathetic-adrenal systems in the early stages of hypertension].", "content": "Changes in the kinin and sympatheticoadrenal systems in the early stages of hypertensive disease were studied in children and adolescents. It was shown that the kinin and sympatheticoadrenal systems take part in the development and formation of primary arterial hypertension; the degree of their changes depends on the stage of the disease. A definite connection was discovered between the kinin, sympatheticoadrenal, and enterochromaffin systems. A change in the activity of one of these systems is attended with a change in the activity of another system.", "contents": "[Role of the kinin and sympathetic-adrenal systems in the early stages of hypertension]. Changes in the kinin and sympatheticoadrenal systems in the early stages of hypertensive disease were studied in children and adolescents. It was shown that the kinin and sympatheticoadrenal systems take part in the development and formation of primary arterial hypertension; the degree of their changes depends on the stage of the disease. A definite connection was discovered between the kinin, sympatheticoadrenal, and enterochromaffin systems. A change in the activity of one of these systems is attended with a change in the activity of another system."}
{"id": "PMID:219289", "title": "Morphology of central nervous system disease in immunosuppressed mice after peripheral herpes simplex virus inoculation. Trigeminal root entry zone.", "content": "Inoculation of mice and rabbits on the cornea with herpes simplex type 1 virus has been shown to cause an ascending infection of the trigeminal nerve, ganglion, and descending tract within the brainstem (2, 3, 7). A discrete, destructive, and primarily demyelinative lesion is seen on the central nervous system side of the trigeminal root entry zone 5 to 8 days after infection (8, 15, 16). This study, utilizing Swiss mice, demonstrated that immunosuppression with cyclophosphamide prior to infection with herpes simplex type virus causes a marked reduction of the mononuclear infiltrate within the central nervous system and a significant decrease in myelin destruction when compared with the infected, nonimmunosuppressed control animals. The content of virus in the brainstem was similar in both groups by day 8 as were the neutralizing antibody titers to herpes simplex type 1 virus. These results suggest that the cellular response plays a definitive role in the destruction of central nervous system tissue after peripheral infection with herpes simplex type 1 virus.", "contents": "Morphology of central nervous system disease in immunosuppressed mice after peripheral herpes simplex virus inoculation. Trigeminal root entry zone. Inoculation of mice and rabbits on the cornea with herpes simplex type 1 virus has been shown to cause an ascending infection of the trigeminal nerve, ganglion, and descending tract within the brainstem (2, 3, 7). A discrete, destructive, and primarily demyelinative lesion is seen on the central nervous system side of the trigeminal root entry zone 5 to 8 days after infection (8, 15, 16). This study, utilizing Swiss mice, demonstrated that immunosuppression with cyclophosphamide prior to infection with herpes simplex type virus causes a marked reduction of the mononuclear infiltrate within the central nervous system and a significant decrease in myelin destruction when compared with the infected, nonimmunosuppressed control animals. The content of virus in the brainstem was similar in both groups by day 8 as were the neutralizing antibody titers to herpes simplex type 1 virus. These results suggest that the cellular response plays a definitive role in the destruction of central nervous system tissue after peripheral infection with herpes simplex type 1 virus."}
{"id": "PMID:219290", "title": "Ultrastructural, biochemical, and immunologic characterization of Mallory bodies in livers of griseofulvin-treated mice. Fimbriated rods of filaments containing prekeratin-like polypeptides.", "content": "Mallory bodies (MBs) induced in hepatocytes by long term feeding of mice with griseofulvin were isolated, purified, and examined by electron microscopy in ultrathin sections and negatively stained preparations. The major structural component of the MBs was randomly oriented, unbranched rods of filaments; these were usually 175 to 250 nm. long and 14 to 20 nm. thick and covered by a dense fimbriate coat of laterally projecting 1.5- to 3-nm. thick threads. Such lateral threads could extend for more than 20 nm. and seemed to be involved in the interconnection of adjacent filaments and their association and aggregation into MBs. Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the purified filament material showed six major polypeptide bands with apparent molecular weights ranging from 48,000 to 66,000. When the portion of the MB filament material that was soluble in solutions containing 8 M urea was allowed to reaggregate upon removal of the urea, an enrichment of one of the polypeptide components (approximate molecular weight, 64,000) was observed. When frozen sections of liver tissue MBs were subjected to indirect immunofluorescence microscopy, they were specifically revealed by guinea pig antibodies directed against purified bovine prekeratin. No significant accumulation of MBs was observed with a series of other antisera, including those containing antibodies against tubulin, actin, and vimentin, the major protein of the intermediate sized filaments predominant in mesenchymal cells. The observations suggest that MBs in livers of griseofulvin-treated mice, and probably also of human alcoholic hepatitis, contain large amounts of prekeratin-like polypeptides which are assembled into a special form of fimbriated rods of 14- to 20-nm. filaments. These filaments are morphologically different from other forms of intermediate sized and thick filaments, including the prekeratin-containing 6- to 11-nm. tonofilament-like filaments present in various epithelial cells.", "contents": "Ultrastructural, biochemical, and immunologic characterization of Mallory bodies in livers of griseofulvin-treated mice. Fimbriated rods of filaments containing prekeratin-like polypeptides. Mallory bodies (MBs) induced in hepatocytes by long term feeding of mice with griseofulvin were isolated, purified, and examined by electron microscopy in ultrathin sections and negatively stained preparations. The major structural component of the MBs was randomly oriented, unbranched rods of filaments; these were usually 175 to 250 nm. long and 14 to 20 nm. thick and covered by a dense fimbriate coat of laterally projecting 1.5- to 3-nm. thick threads. Such lateral threads could extend for more than 20 nm. and seemed to be involved in the interconnection of adjacent filaments and their association and aggregation into MBs. Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the purified filament material showed six major polypeptide bands with apparent molecular weights ranging from 48,000 to 66,000. When the portion of the MB filament material that was soluble in solutions containing 8 M urea was allowed to reaggregate upon removal of the urea, an enrichment of one of the polypeptide components (approximate molecular weight, 64,000) was observed. When frozen sections of liver tissue MBs were subjected to indirect immunofluorescence microscopy, they were specifically revealed by guinea pig antibodies directed against purified bovine prekeratin. No significant accumulation of MBs was observed with a series of other antisera, including those containing antibodies against tubulin, actin, and vimentin, the major protein of the intermediate sized filaments predominant in mesenchymal cells. The observations suggest that MBs in livers of griseofulvin-treated mice, and probably also of human alcoholic hepatitis, contain large amounts of prekeratin-like polypeptides which are assembled into a special form of fimbriated rods of 14- to 20-nm. filaments. These filaments are morphologically different from other forms of intermediate sized and thick filaments, including the prekeratin-containing 6- to 11-nm. tonofilament-like filaments present in various epithelial cells."}
{"id": "PMID:219292", "title": "Regulation of the receptor-mediated cyclic AMP response of kidney to parathyroid hormone in the vitamin D-deficient rat.", "content": "Rats fed a diet deficient in vitamin D were found to exhibit a refractory cyclic AMP response of kidney slices to parathyroid hormone and a marked decrease in membrane parathyroid hormone-dependent adenylate cyclase activity. Both the characteristic calcium deficiency (hypocalcemia) and secondary elevation of circulating parathyroid hormone appeared before the first noticeable decrease in hormone-dependent enzyme activity. After repletion of D-deficient rats with vitamin D2, we found that serum calcium and parathyroid hormone were both restored to normal levels before the depressed enzyme response to the hormone was reversed. Moreover, infusion of parthyroid hormone into vitamin D-replete rats led to a marked reduction in parathyroid hormone-dependent adenylate cyclase activity, which was partly restored to control level 3 hours after discontinuing the hormone infusion. Taken as a whole, this study suggests that the elevated endogenous parathyroid hormone in the vitamin D-deficient rat is involved in the \"down-regulation\" of renal cyclic AMP responsiveness to the hormone. However, these experiments do not rule out the possibility that calcium deficiency and/or vitamin D per se participate in the regulation of the renal cyclic AMP response to parathyroid hormone.", "contents": "Regulation of the receptor-mediated cyclic AMP response of kidney to parathyroid hormone in the vitamin D-deficient rat. Rats fed a diet deficient in vitamin D were found to exhibit a refractory cyclic AMP response of kidney slices to parathyroid hormone and a marked decrease in membrane parathyroid hormone-dependent adenylate cyclase activity. Both the characteristic calcium deficiency (hypocalcemia) and secondary elevation of circulating parathyroid hormone appeared before the first noticeable decrease in hormone-dependent enzyme activity. After repletion of D-deficient rats with vitamin D2, we found that serum calcium and parathyroid hormone were both restored to normal levels before the depressed enzyme response to the hormone was reversed. Moreover, infusion of parthyroid hormone into vitamin D-replete rats led to a marked reduction in parathyroid hormone-dependent adenylate cyclase activity, which was partly restored to control level 3 hours after discontinuing the hormone infusion. Taken as a whole, this study suggests that the elevated endogenous parathyroid hormone in the vitamin D-deficient rat is involved in the \"down-regulation\" of renal cyclic AMP responsiveness to the hormone. However, these experiments do not rule out the possibility that calcium deficiency and/or vitamin D per se participate in the regulation of the renal cyclic AMP response to parathyroid hormone."}
{"id": "PMID:219293", "title": "Catecholamine binding to CNS adrenergic receptors.", "content": "The properties of 3H-catecholamine binding to alpha- and beta-adrenergic receptors in CNS are reviewed. 3H-epinephrine and 3H-norepinephrine label one class of alpha-receptors throughout the brain, with high affinities for agonists and some antagonists. Agonist affinities at this site are increased in low temperature conditions but are reduced by guanine nucleotides and monovalent cations. Divalent cations reverse both effects. This alpha-receptor may be coupled to adenylate cyclase by GTP and/or sodium, and uncoupled by divalent cations. 3H-epinephrine labels beta2, but not beta1, receptors in CNS, especially in bovine cerebellum. The same beta-receptor does not show agonist-specific GTP-sensitivity, but does exhibit Na+-sensitivity. This receptor appears to be linked to adenylate cyclase, and sodium rather than GTP may be the coupling agent.", "contents": "Catecholamine binding to CNS adrenergic receptors. The properties of 3H-catecholamine binding to alpha- and beta-adrenergic receptors in CNS are reviewed. 3H-epinephrine and 3H-norepinephrine label one class of alpha-receptors throughout the brain, with high affinities for agonists and some antagonists. Agonist affinities at this site are increased in low temperature conditions but are reduced by guanine nucleotides and monovalent cations. Divalent cations reverse both effects. This alpha-receptor may be coupled to adenylate cyclase by GTP and/or sodium, and uncoupled by divalent cations. 3H-epinephrine labels beta2, but not beta1, receptors in CNS, especially in bovine cerebellum. The same beta-receptor does not show agonist-specific GTP-sensitivity, but does exhibit Na+-sensitivity. This receptor appears to be linked to adenylate cyclase, and sodium rather than GTP may be the coupling agent."}
{"id": "PMID:219294", "title": "The Escherichia coli adenylate cyclase complex: activation by phosphoenolpyruvate.", "content": "A model for the regulation of the activity of Escherichia coli adenylate cyclase is presented. It is proposed that Enzyme I of the phosphoenolpyruvate:sugar phosphotransferase system (PTS) interacts in a regulatory sense with the catalytic unit of adenylate cyclase. The phosphoenolpyruvate (PEP)-dependent phosphorylation of Enzyme I is assumed to be associated with a high activity state of adenylate cyclase. The pyruvate or sugar-dependent dephosphorylation of Enzyme I is correlated with a low activity state of adenylate cyclase. Evidence in support of the proposed model involves the observation that Enzyme I mutants have low cAMP levels and that PEP increases cellular cAMP levels and, under certain conditions, activates adenylate cyclase, Kinetic studies indicate that various ligands have opposing effects on adenylate cyclase. While PEP activates the enzyme, either glucose or pyruvate inhibit it. The unique relationships of PEP and Enzyme I to adenylate cyclase activity are discussed.", "contents": "The Escherichia coli adenylate cyclase complex: activation by phosphoenolpyruvate. A model for the regulation of the activity of Escherichia coli adenylate cyclase is presented. It is proposed that Enzyme I of the phosphoenolpyruvate:sugar phosphotransferase system (PTS) interacts in a regulatory sense with the catalytic unit of adenylate cyclase. The phosphoenolpyruvate (PEP)-dependent phosphorylation of Enzyme I is assumed to be associated with a high activity state of adenylate cyclase. The pyruvate or sugar-dependent dephosphorylation of Enzyme I is correlated with a low activity state of adenylate cyclase. Evidence in support of the proposed model involves the observation that Enzyme I mutants have low cAMP levels and that PEP increases cellular cAMP levels and, under certain conditions, activates adenylate cyclase, Kinetic studies indicate that various ligands have opposing effects on adenylate cyclase. While PEP activates the enzyme, either glucose or pyruvate inhibit it. The unique relationships of PEP and Enzyme I to adenylate cyclase activity are discussed."}
{"id": "PMID:219295", "title": "An avidin-biotinyl-propranolol complex for beta-adrenergic receptor characterization.", "content": "The synthesis of biotinyl-hexaglycyl-NEDA (abbreviation:BGN), a biotinyl derivative of propranolol, is described. This bifunctional molecule binds with high affinity to the biotin-binding protein, avidin. The duck erythrocyte was used as a model beta-receptor system. Formation of an avidin-BGN-beta-receptor complex was demonstrated in intact erythrocytes, in erythrocyte ghosts, and in the digitonin-solubilized beta-receptor. The avidin-BGN complex will be used for localization and purification of the beta-receptor.", "contents": "An avidin-biotinyl-propranolol complex for beta-adrenergic receptor characterization. The synthesis of biotinyl-hexaglycyl-NEDA (abbreviation:BGN), a biotinyl derivative of propranolol, is described. This bifunctional molecule binds with high affinity to the biotin-binding protein, avidin. The duck erythrocyte was used as a model beta-receptor system. Formation of an avidin-BGN-beta-receptor complex was demonstrated in intact erythrocytes, in erythrocyte ghosts, and in the digitonin-solubilized beta-receptor. The avidin-BGN complex will be used for localization and purification of the beta-receptor."}
{"id": "PMID:219296", "title": "Spin label studies on rat liver and heart plasma membranes: effects of temperature, calcium, and lanthanum on membrane fluidity.", "content": "The structures of rat liver and heart plasma membranes were studied with the 5-nitroxide stearic acid spin probe, I(12,3). The polarity-corrected order parameters (S) of liver and heart plasma membranes were independent of probe concentration only if experimentally determined low I(12,3)/lipid ratios were employed. At higher probe/lipid ratios, the order parameters of both membrane systems decreased with increasing probe concentration, and these effects were attributed to enhanced nitroxide radical interactions. Examination of the temperature dependence of approximate and polarity-corrected order parameters indicated that lipid phase separations occur in liver (between 19 degrees and 28 degrees C) and heart (between 21 degrees and 32 degrees C) plasma membranes. The possibility that a wide variety of membrane-associated functions may be influenced by these thermotropic phase separations is considered. Addition of 3.9 mM CaCl2 to I(12,3)-labeled liver plasma membrane decreased the fluidity as indicated by a 5% increase in S at 37 degrees C. Similarly, titrating I(12,3)-labeled heart plasma membranes with either CaCl2 or LaCl3 decreased the lipid fluidity at 37 degrees C, although the magnitude of the La3+ effect was larger and occurred at lower concentrations than that induced by Ca2+; addition of 0.2 mM La3+ or 3.2 mM Ca2+ increased S by approximately 7% and 5%, respectively. The above cation effects reflected only alterations in the membrane fluidity and were not due to changes in probe--probe interactions. Ca2+ and La3+ at these concentrations decrease the activities of such plasma membrane enzymes as Na+, K+-ATPase and adenylyl cyclase, and it is suggested that the inhibition of these enzymes may be due in part to cation-mediated decreases in the lipid fluidity.", "contents": "Spin label studies on rat liver and heart plasma membranes: effects of temperature, calcium, and lanthanum on membrane fluidity. The structures of rat liver and heart plasma membranes were studied with the 5-nitroxide stearic acid spin probe, I(12,3). The polarity-corrected order parameters (S) of liver and heart plasma membranes were independent of probe concentration only if experimentally determined low I(12,3)/lipid ratios were employed. At higher probe/lipid ratios, the order parameters of both membrane systems decreased with increasing probe concentration, and these effects were attributed to enhanced nitroxide radical interactions. Examination of the temperature dependence of approximate and polarity-corrected order parameters indicated that lipid phase separations occur in liver (between 19 degrees and 28 degrees C) and heart (between 21 degrees and 32 degrees C) plasma membranes. The possibility that a wide variety of membrane-associated functions may be influenced by these thermotropic phase separations is considered. Addition of 3.9 mM CaCl2 to I(12,3)-labeled liver plasma membrane decreased the fluidity as indicated by a 5% increase in S at 37 degrees C. Similarly, titrating I(12,3)-labeled heart plasma membranes with either CaCl2 or LaCl3 decreased the lipid fluidity at 37 degrees C, although the magnitude of the La3+ effect was larger and occurred at lower concentrations than that induced by Ca2+; addition of 0.2 mM La3+ or 3.2 mM Ca2+ increased S by approximately 7% and 5%, respectively. The above cation effects reflected only alterations in the membrane fluidity and were not due to changes in probe--probe interactions. Ca2+ and La3+ at these concentrations decrease the activities of such plasma membrane enzymes as Na+, K+-ATPase and adenylyl cyclase, and it is suggested that the inhibition of these enzymes may be due in part to cation-mediated decreases in the lipid fluidity."}
{"id": "PMID:219297", "title": "A serological assay for the detection of cell surface receptors of nerve growth factor.", "content": "When single-cell suspensions prepared from embryonic day 8 (E8) chick sensory ganglia are incubated with nerve growth factor (NGF), anti-NGF antiserum, and complement, an NGF-dependent cytotoxic kill of 20 (+/- 3)% of the ganglia cells is observed. This percentage is increased by a factor of two when only the neuronal cells are tested. No kill is observed on the nonneuronal cell population representing 50% of the ganglia dissociate. When E8 sensory ganglia cells are cultured in the presence of NGF following cytotoxic kill, the large, phase-bright NGF-reponsive neurons are missing from the culture. These results indicate that the cells recognized in the cytotoxicity assay have to carry NGF-binding sites of type I, which is the one with the higher affinity of the two types of NGF-binding sites (I and II) present on sensory ganglia cells. This conclusion is further supported by the following data: a) half maximal cytotoxicity is reached already at a concentration of NGF which is below the KD of binding site I; b) a washing step which removes all NGF bound to type II receptors while leaving a high percentage of type I receptors occupied has no effect on the percentage of ganglia cells killed. Using the cytotoxicity assay the presence of high-affinity binding sites of type I can be demonstrated on sensory ganglia cells from E8 chick embryos but not from E4 embryos and not on liver and heart cells from E8 embryos. Further, type I receptor-bearing cells were detectable in the brain using this assay. At E8, NGF receptors could be detected on cells of the forebrain and the tectum but not on brain stem cells. Cytotoxic kill of forebrain cells was found to be especially high at E8 and E9, and decreased by E10.", "contents": "A serological assay for the detection of cell surface receptors of nerve growth factor. When single-cell suspensions prepared from embryonic day 8 (E8) chick sensory ganglia are incubated with nerve growth factor (NGF), anti-NGF antiserum, and complement, an NGF-dependent cytotoxic kill of 20 (+/- 3)% of the ganglia cells is observed. This percentage is increased by a factor of two when only the neuronal cells are tested. No kill is observed on the nonneuronal cell population representing 50% of the ganglia dissociate. When E8 sensory ganglia cells are cultured in the presence of NGF following cytotoxic kill, the large, phase-bright NGF-reponsive neurons are missing from the culture. These results indicate that the cells recognized in the cytotoxicity assay have to carry NGF-binding sites of type I, which is the one with the higher affinity of the two types of NGF-binding sites (I and II) present on sensory ganglia cells. This conclusion is further supported by the following data: a) half maximal cytotoxicity is reached already at a concentration of NGF which is below the KD of binding site I; b) a washing step which removes all NGF bound to type II receptors while leaving a high percentage of type I receptors occupied has no effect on the percentage of ganglia cells killed. Using the cytotoxicity assay the presence of high-affinity binding sites of type I can be demonstrated on sensory ganglia cells from E8 chick embryos but not from E4 embryos and not on liver and heart cells from E8 embryos. Further, type I receptor-bearing cells were detectable in the brain using this assay. At E8, NGF receptors could be detected on cells of the forebrain and the tectum but not on brain stem cells. Cytotoxic kill of forebrain cells was found to be especially high at E8 and E9, and decreased by E10."}
{"id": "PMID:219298", "title": "Photolabile and paramagnetic reagents for the investigation of transmembrane signaling events.", "content": "To investigate the dynamics of membrane processes that may be integral components of specific transmembrane signaling events we have synthesized several novel paramagnetic probes and their photoreactive counterparts. The structure of these probes was designed to (1) restrict \"flipping\" across the membrane bilayer; (2) contain paramagnetic or photoreactive moieties that could be placed at specific depths within the bilayer; (3) provide information about membrane structure as well as dynamics of protein movement; and (4) in the case of the photoreactive probes, be of high specific radioactivity. The molecules described in this paper consist of amino acid, dipeptide, or carbohydrate groups attached to arylazide- or nitroxide-bearing fatty acids. The synthesis and initial characterization of these membrane probes is described.", "contents": "Photolabile and paramagnetic reagents for the investigation of transmembrane signaling events. To investigate the dynamics of membrane processes that may be integral components of specific transmembrane signaling events we have synthesized several novel paramagnetic probes and their photoreactive counterparts. The structure of these probes was designed to (1) restrict \"flipping\" across the membrane bilayer; (2) contain paramagnetic or photoreactive moieties that could be placed at specific depths within the bilayer; (3) provide information about membrane structure as well as dynamics of protein movement; and (4) in the case of the photoreactive probes, be of high specific radioactivity. The molecules described in this paper consist of amino acid, dipeptide, or carbohydrate groups attached to arylazide- or nitroxide-bearing fatty acids. The synthesis and initial characterization of these membrane probes is described."}
{"id": "PMID:219299", "title": "Redistribution of intramembrane particles of human erythrocytes induced by HVJ (Sendai virus): a prerequisite for the virus-induced cell fusion.", "content": "Aggregation of intramembrane particles of human erythrocytes was found to be induced by HVJ (Sendai virus) under conditions which lead to cell fusion. Degree of polyerythrocyte formation was compared under a variety of conditions with extent of cluster formation observed with the same preparations. Both structural changes of the membranes, ie, fusion and clustering of the particles, behaved very similarly under widely different virus-to-cell ratios and over the time course of cell fusion. Furthermore, by inclusion of high concentrations of antispectrin antibodies within the ghosts, inhibition of clustering of intramembrane particles and hindrance of virus-induced cell fusion were found to occur simultaneously. Antibodies by themselves did not induce aggregation of particles under isotonic conditions, whereas particle clustering could be induced under hypotonic conditions at antibody concentrations causing partial cross-linking of spectrin molecules. In conclusion, clustering of intramembrane particles seems to be required for virus-induced fusion of human erythrocytes.", "contents": "Redistribution of intramembrane particles of human erythrocytes induced by HVJ (Sendai virus): a prerequisite for the virus-induced cell fusion. Aggregation of intramembrane particles of human erythrocytes was found to be induced by HVJ (Sendai virus) under conditions which lead to cell fusion. Degree of polyerythrocyte formation was compared under a variety of conditions with extent of cluster formation observed with the same preparations. Both structural changes of the membranes, ie, fusion and clustering of the particles, behaved very similarly under widely different virus-to-cell ratios and over the time course of cell fusion. Furthermore, by inclusion of high concentrations of antispectrin antibodies within the ghosts, inhibition of clustering of intramembrane particles and hindrance of virus-induced cell fusion were found to occur simultaneously. Antibodies by themselves did not induce aggregation of particles under isotonic conditions, whereas particle clustering could be induced under hypotonic conditions at antibody concentrations causing partial cross-linking of spectrin molecules. In conclusion, clustering of intramembrane particles seems to be required for virus-induced fusion of human erythrocytes."}
{"id": "PMID:219300", "title": "Development of carcinoma of the breast at the site of an implanted pacemaker in two patients.", "content": "We report here on two female patients who had permanent pacemakers implanted in their chests and who developed carcinoma of the breast subsequently. An association is suspected between the breast cancer and the pacemaker, which is implanted in an area which borders with the mammary gland or is even right within it. This suspicion led us lately to change in female patients the site of the subcutaneous pocket for the implantation of the pacemaker to a position higher in the chest than before. Moreover, we advocate frequent breast examinations in all female patients with implanted pacemakers.", "contents": "Development of carcinoma of the breast at the site of an implanted pacemaker in two patients. We report here on two female patients who had permanent pacemakers implanted in their chests and who developed carcinoma of the breast subsequently. An association is suspected between the breast cancer and the pacemaker, which is implanted in an area which borders with the mammary gland or is even right within it. This suspicion led us lately to change in female patients the site of the subcutaneous pocket for the implantation of the pacemaker to a position higher in the chest than before. Moreover, we advocate frequent breast examinations in all female patients with implanted pacemakers."}
{"id": "PMID:219301", "title": "The relationship between sIgM positive lymph-node lymphocytes and breast cancer metastasis.", "content": "The relative frequency of lymphocytes with surface immunoglobulins (sIgM, sIgG, sIgA) was studied in breast-cancer patients' axillary lymph nodes by the immunofluorescence technique. The study encompassed a total of 105 patients, most of whom had infiltrating ductal carcinoma (IDC). The results have indicated a significantly higher (p less than 0.005) average percentage of sIgM positive lymphocytes in lymph nodes in the group of IDC patients with lymph-node metastasis. Short-term followup was available for a limited number of patients, but no conclusions were reached with respect to sIgM positive lymphocytes. It is suggested that evaluation of axillary lymph-node and peripheral blood lymphocyte subpopulations for each cancer patient would provide new information which could aid in determining the extent of the disease process. Moreover, such information may be of assistance in decisions of therapeutic modalities, detection of occult metastasis, and prediction of prognosis.", "contents": "The relationship between sIgM positive lymph-node lymphocytes and breast cancer metastasis. The relative frequency of lymphocytes with surface immunoglobulins (sIgM, sIgG, sIgA) was studied in breast-cancer patients' axillary lymph nodes by the immunofluorescence technique. The study encompassed a total of 105 patients, most of whom had infiltrating ductal carcinoma (IDC). The results have indicated a significantly higher (p less than 0.005) average percentage of sIgM positive lymphocytes in lymph nodes in the group of IDC patients with lymph-node metastasis. Short-term followup was available for a limited number of patients, but no conclusions were reached with respect to sIgM positive lymphocytes. It is suggested that evaluation of axillary lymph-node and peripheral blood lymphocyte subpopulations for each cancer patient would provide new information which could aid in determining the extent of the disease process. Moreover, such information may be of assistance in decisions of therapeutic modalities, detection of occult metastasis, and prediction of prognosis."}
{"id": "PMID:219302", "title": "Etiology of pediatric gastroenteritis in Rochester, Minnesota.", "content": "The cause of diarrhea in a Rochester, Minnesota, pediatric population was studied by examining specimens for the presence of enterotoxigenic strains of Escherichia coli and reovirus-like agents, in addition to parasites and other bacteria and viruses. Reovirus-like agents were detected by electron microscopy in the feces of 11 of 31 patients, but none was found from specimens collected during convalescence or from 16 asymptomatic matched controls (P less than 0.01). Infection due to reovirus-like agents occurred significantly more often during the winter months in patients 6 to 18 months of age. Vomiting and diarrhea most often occurred simultaneously. All patients recovered without significant complications or sequelae, although one child was hospitalized for 3 days. Mean duration of illness was 9 days. No enterotoxigenic strains of E. coli were detected from symptomatic or control groups. Our results show that of the 16 organisms detected in stool specimens (11 reovirus-like agents, 3 salmonellae, and single isolates of adenovirus and enterovirus), the reovirus-like agent was the most frequent (69%) and was the probable etiologic agent in 35% of the cases of diarrhea in Rochester children.", "contents": "Etiology of pediatric gastroenteritis in Rochester, Minnesota. The cause of diarrhea in a Rochester, Minnesota, pediatric population was studied by examining specimens for the presence of enterotoxigenic strains of Escherichia coli and reovirus-like agents, in addition to parasites and other bacteria and viruses. Reovirus-like agents were detected by electron microscopy in the feces of 11 of 31 patients, but none was found from specimens collected during convalescence or from 16 asymptomatic matched controls (P less than 0.01). Infection due to reovirus-like agents occurred significantly more often during the winter months in patients 6 to 18 months of age. Vomiting and diarrhea most often occurred simultaneously. All patients recovered without significant complications or sequelae, although one child was hospitalized for 3 days. Mean duration of illness was 9 days. No enterotoxigenic strains of E. coli were detected from symptomatic or control groups. Our results show that of the 16 organisms detected in stool specimens (11 reovirus-like agents, 3 salmonellae, and single isolates of adenovirus and enterovirus), the reovirus-like agent was the most frequent (69%) and was the probable etiologic agent in 35% of the cases of diarrhea in Rochester children."}
{"id": "PMID:219303", "title": "[Ectopic ACTH syndrome in bronchopulmonary tumors (author's transl)].", "content": "Thirteen cases of bronchopulmonary carcinomas without symptoms of hypercorticoidism, hypopotassemic alkalosis, or intolerance to an overdose of glucose are described. Repeated circadian rhythm and the suppression test with small doses of dexamethasone were practiced on each one. In 7 cases the secretion of cortisol was supressed normally with oral administration of dexametahsone. In the other 6 cases the circadian rhythm was lost and it was imposible to reduce the plasma level of cortisol with dexamethasone. The results help to point out the usefulness of these easy to perform dynamic tests as a means of diagnosing the ectopic production of ACTH by bronchopulmonary tumors. At the same time they show the relatively high incidence of production of this hormone by this type of tumors in patients who have no symptoms of classical hypercorticoidism. The determination of plasma cortisol levels using this test could be valuable in establishing the prognosis and clinical course of the disease. A normalization of the endogenous adrenal secretion of glucocorticoids would indicate a regression of the tumor in response to treatment.", "contents": "[Ectopic ACTH syndrome in bronchopulmonary tumors (author's transl)]. Thirteen cases of bronchopulmonary carcinomas without symptoms of hypercorticoidism, hypopotassemic alkalosis, or intolerance to an overdose of glucose are described. Repeated circadian rhythm and the suppression test with small doses of dexamethasone were practiced on each one. In 7 cases the secretion of cortisol was supressed normally with oral administration of dexametahsone. In the other 6 cases the circadian rhythm was lost and it was imposible to reduce the plasma level of cortisol with dexamethasone. The results help to point out the usefulness of these easy to perform dynamic tests as a means of diagnosing the ectopic production of ACTH by bronchopulmonary tumors. At the same time they show the relatively high incidence of production of this hormone by this type of tumors in patients who have no symptoms of classical hypercorticoidism. The determination of plasma cortisol levels using this test could be valuable in establishing the prognosis and clinical course of the disease. A normalization of the endogenous adrenal secretion of glucocorticoids would indicate a regression of the tumor in response to treatment."}
{"id": "PMID:219304", "title": "[Acute abdomen due to hemoperitoneum as the first manifestation of a liver tumor. Report of four cases (author's transl)].", "content": "Four cases of spontaneous acute hemoperitoneum due to rupture of a liver tumor are presented. The resulting acute abdomen was the first manifestation of the neoplasia. The four tumors corresponded histopathologically to a cavernous hemangioma, a bening adenoma related to anabolizing androgens, and two hepatocarcinomas in cirrhotic livers. All of the patients presented abdominal pain and shock, the characteristics of which are described in this report. One of the patients died due to cardiac arrest before surgical treatment. Emergency surgery was performed on the other three, consisting of left hepatic lobectomy and ligature of the hepatic artery for the hemengioma, and segmented hepatectomy for the adenoma and the hepatocarcinoma. Only the patient with benign tumor survived. Lastly, the authors review the literature, commenting on the clinical, physiopathologic, therapeutic, and prognostic aspects.", "contents": "[Acute abdomen due to hemoperitoneum as the first manifestation of a liver tumor. Report of four cases (author's transl)]. Four cases of spontaneous acute hemoperitoneum due to rupture of a liver tumor are presented. The resulting acute abdomen was the first manifestation of the neoplasia. The four tumors corresponded histopathologically to a cavernous hemangioma, a bening adenoma related to anabolizing androgens, and two hepatocarcinomas in cirrhotic livers. All of the patients presented abdominal pain and shock, the characteristics of which are described in this report. One of the patients died due to cardiac arrest before surgical treatment. Emergency surgery was performed on the other three, consisting of left hepatic lobectomy and ligature of the hepatic artery for the hemengioma, and segmented hepatectomy for the adenoma and the hepatocarcinoma. Only the patient with benign tumor survived. Lastly, the authors review the literature, commenting on the clinical, physiopathologic, therapeutic, and prognostic aspects."}
{"id": "PMID:219305", "title": "[Immunoblastic sarcoma (author's transl)].", "content": "A case of immunoblastic sarcoma in a 56-year-old man is presented. He had no history of predisposing diseases. His clinical condition was typical of a highly aggressive disseminated malignant lymphoma and he presented important heterogenous hypergammaglobulinemia. The patient died 9 months after the onset of the disease, following brief and incomplete response to various chemotherapeutic associations. The importance of cytological and cytochemical studies of lymph node by touch prep is stressed, since this condition could have been misdiagnosed, in our case, with a malignant histiocytosis. The cell proliferation was shown cytochemically to be of B-lymphoid origin, not histiocytic. It was a monomorphic and nearly massive proliferation of large, intensely basophilic, nonphagocytolytic cells; reactions to naphthol-As-D-acetate esterase, acid phosphatase, beta-glucuronidase, and Perl's stain were negative. The relatively few phagocytolytic cells were shown cytochemically to be normal, true histiocytes, not identifiable with the atypical proliferating cells. This was an essential fact in establishing the diagnosis of immunoblastic sarcoma. In light of today's knowledge, the authors believe that immunoblastic sarcoma is a lymphomatous condition which should be distinguished from centroblastic lymphadenopathy. Lastly, they comment on a retropsective study of lymphomas previously catalogued as reticulo-sarcomas, which has shown that the majority of cases were centroblastic lymphomas and some were immunoblastic sarcomas.", "contents": "[Immunoblastic sarcoma (author's transl)]. A case of immunoblastic sarcoma in a 56-year-old man is presented. He had no history of predisposing diseases. His clinical condition was typical of a highly aggressive disseminated malignant lymphoma and he presented important heterogenous hypergammaglobulinemia. The patient died 9 months after the onset of the disease, following brief and incomplete response to various chemotherapeutic associations. The importance of cytological and cytochemical studies of lymph node by touch prep is stressed, since this condition could have been misdiagnosed, in our case, with a malignant histiocytosis. The cell proliferation was shown cytochemically to be of B-lymphoid origin, not histiocytic. It was a monomorphic and nearly massive proliferation of large, intensely basophilic, nonphagocytolytic cells; reactions to naphthol-As-D-acetate esterase, acid phosphatase, beta-glucuronidase, and Perl's stain were negative. The relatively few phagocytolytic cells were shown cytochemically to be normal, true histiocytes, not identifiable with the atypical proliferating cells. This was an essential fact in establishing the diagnosis of immunoblastic sarcoma. In light of today's knowledge, the authors believe that immunoblastic sarcoma is a lymphomatous condition which should be distinguished from centroblastic lymphadenopathy. Lastly, they comment on a retropsective study of lymphomas previously catalogued as reticulo-sarcomas, which has shown that the majority of cases were centroblastic lymphomas and some were immunoblastic sarcomas."}
{"id": "PMID:219319", "title": "Progressive systemic sclerosis (PSS) and malignancy, pulmonary and non-pulmonary.", "content": "In contrast to the 15-20% incidence of the coexistence of acute dermatomyositis-polymyositis and malignancy, it has been accepted traditionally that the association of progressive systemic sclerosis, a disease with several features that may overlap the former condition, and malignancy is purely fortuitous. This experience has not been altered by the material presented in this review. However, the factual coexistence has been illuminated by a review of the pertinent literature and presentation of 12 previously unpublished case reports. Four cases concern pulmonary malignancies in PSS; eight are of an associated non-pulmonary malignancy. In the first group, the development of a malignancy superimposed on the chronic fibrosing changes in the lungs of PSS does not seem so strange, particularly in view of a possible immunologic reaction by collagen in considering pathogenesis. This immunologic process might be similar to a related immunologic process responsible for the development of malignant cells in pulmonary and other tissue, where normal cells usually are found. The high incidence of males is related to the high incidence of males in Veterans Administration Hospitals, the principal population source of these cases.", "contents": "Progressive systemic sclerosis (PSS) and malignancy, pulmonary and non-pulmonary. In contrast to the 15-20% incidence of the coexistence of acute dermatomyositis-polymyositis and malignancy, it has been accepted traditionally that the association of progressive systemic sclerosis, a disease with several features that may overlap the former condition, and malignancy is purely fortuitous. This experience has not been altered by the material presented in this review. However, the factual coexistence has been illuminated by a review of the pertinent literature and presentation of 12 previously unpublished case reports. Four cases concern pulmonary malignancies in PSS; eight are of an associated non-pulmonary malignancy. In the first group, the development of a malignancy superimposed on the chronic fibrosing changes in the lungs of PSS does not seem so strange, particularly in view of a possible immunologic reaction by collagen in considering pathogenesis. This immunologic process might be similar to a related immunologic process responsible for the development of malignant cells in pulmonary and other tissue, where normal cells usually are found. The high incidence of males is related to the high incidence of males in Veterans Administration Hospitals, the principal population source of these cases."}
{"id": "PMID:219321", "title": "The penetration of the embedding medium methyl methacrylate in undecalcified bone.", "content": "Cutting artifacts in microtome sections prepared from undemineralized methyl methacrylate embedded bone are due to the almost complete absence of methacrylate in the intercellular compartment of the bone tissue, the soft tissues being fully impregnated with the polymer. The osteocyte system is only partially penetrated by methacrylate.", "contents": "The penetration of the embedding medium methyl methacrylate in undecalcified bone. Cutting artifacts in microtome sections prepared from undemineralized methyl methacrylate embedded bone are due to the almost complete absence of methacrylate in the intercellular compartment of the bone tissue, the soft tissues being fully impregnated with the polymer. The osteocyte system is only partially penetrated by methacrylate."}
{"id": "PMID:219322", "title": "Recognition of viral antigens in 6/94 virus-induced T-cell-mediated cytotoxicity.", "content": "Distinct events in the virus-stimulated T-cell-mediated cytotoxicity (V-CMC) have been investigated: 1.) The induction of V-CMC is possible by immunizing mice with infectious as well as UV-inactivated virus (parainfluenza type 1 strain 6/94), or with virus-infected cells either compatible or imcompatible with the recipient. 2). Recognition of viral antigens by the effector cells occurs independently of the H2 environment: Fractionation of effector cells on columns loaded with virus-infected cells eliminates virus-specific cytotoxic cells. Effector cells and cells on the column need not share H-2 antigens. The findings are discussed with regard to the H2 restriction of the virus induced T-cells mediated cytotoxicity.", "contents": "Recognition of viral antigens in 6/94 virus-induced T-cell-mediated cytotoxicity. Distinct events in the virus-stimulated T-cell-mediated cytotoxicity (V-CMC) have been investigated: 1.) The induction of V-CMC is possible by immunizing mice with infectious as well as UV-inactivated virus (parainfluenza type 1 strain 6/94), or with virus-infected cells either compatible or imcompatible with the recipient. 2). Recognition of viral antigens by the effector cells occurs independently of the H2 environment: Fractionation of effector cells on columns loaded with virus-infected cells eliminates virus-specific cytotoxic cells. Effector cells and cells on the column need not share H-2 antigens. The findings are discussed with regard to the H2 restriction of the virus induced T-cells mediated cytotoxicity."}
{"id": "PMID:219323", "title": "No homology detectable between Marek's disease virus (MDV) DNA and herpesvirus of the turkey (HVT) DNA.", "content": "The relation of four different strains of MDV and two strains of HVT was analyzed by gel electrophoresis of viral DNA digested by various restriction endonucleases and by filter hybridization of viral DNA with complementary RNA. The four MDV strains showed fragment patterns completely different from those of HVT upon digestion of the viral DNA with Bam H I, Eco R I, Hind III, Hpa, I, and Xho and separation of fragments on agarose gels. The cleavage patterns of the four MDV strains showed great similarities among each other as well as some differences between the individual strains. In the cleavage patterns of HVT a similar close relationship was observed between the two HVT strains with slight divergence between both. Filter hybridizations of viral DNA with labelled complementary RNA prepared from the DNA of the GA strain of MDV or from the DNA of the PH-THV1 strain of HVT revealed no cross-hybridization between the MDV and the HVT strains. cRNA prepared from the DNA of an MDV strain hybridized only to restriction enzyme fragments of the MDV strains transferred to nitrocellulose filters, but not to fragments of HVT DNA, and vice versa.", "contents": "No homology detectable between Marek's disease virus (MDV) DNA and herpesvirus of the turkey (HVT) DNA. The relation of four different strains of MDV and two strains of HVT was analyzed by gel electrophoresis of viral DNA digested by various restriction endonucleases and by filter hybridization of viral DNA with complementary RNA. The four MDV strains showed fragment patterns completely different from those of HVT upon digestion of the viral DNA with Bam H I, Eco R I, Hind III, Hpa, I, and Xho and separation of fragments on agarose gels. The cleavage patterns of the four MDV strains showed great similarities among each other as well as some differences between the individual strains. In the cleavage patterns of HVT a similar close relationship was observed between the two HVT strains with slight divergence between both. Filter hybridizations of viral DNA with labelled complementary RNA prepared from the DNA of the GA strain of MDV or from the DNA of the PH-THV1 strain of HVT revealed no cross-hybridization between the MDV and the HVT strains. cRNA prepared from the DNA of an MDV strain hybridized only to restriction enzyme fragments of the MDV strains transferred to nitrocellulose filters, but not to fragments of HVT DNA, and vice versa."}
{"id": "PMID:219324", "title": "[Ductal carcinoma of the salivary glands. Case report].", "content": "A rare case of carcinoma of the salivary gland ducts highlights potential clinical malignity and the need for adequate therapeutic action, aimed above all at preventing the onset of recurrences and metastasis, including cases which have been clearly differentiated histologically.", "contents": "[Ductal carcinoma of the salivary glands. Case report]. A rare case of carcinoma of the salivary gland ducts highlights potential clinical malignity and the need for adequate therapeutic action, aimed above all at preventing the onset of recurrences and metastasis, including cases which have been clearly differentiated histologically."}
{"id": "PMID:219328", "title": "[Morphogenesis of intracytoplasmic oncornaviruses].", "content": "Intracytoplasmic oncorna viruses type-A are de novo formed in the cytoplasma, independently of the organella. In the early phase of the morphologenesis an electrondense patch-like area and the disappearence of the ribosomes can be observed. Double-membrane structures consisting of gylcoprotein can be seen in form of segments, horseshoes or rings. In the centre of the viruses ribosoma-like inclusions may be observed. Viruses of tubular structure appear to be of peculiar forms of the formation of crystals, the mechanism of which is yet unknown.", "contents": "[Morphogenesis of intracytoplasmic oncornaviruses]. Intracytoplasmic oncorna viruses type-A are de novo formed in the cytoplasma, independently of the organella. In the early phase of the morphologenesis an electrondense patch-like area and the disappearence of the ribosomes can be observed. Double-membrane structures consisting of gylcoprotein can be seen in form of segments, horseshoes or rings. In the centre of the viruses ribosoma-like inclusions may be observed. Viruses of tubular structure appear to be of peculiar forms of the formation of crystals, the mechanism of which is yet unknown."}
{"id": "PMID:219329", "title": "[Similarities between cultured human fetal glia cells and cell types from gliomas; cell culture studies].", "content": "Authors carried out a comparative study of cell-cultures of human fetal brain tissue and gliomas of various histological structures. In 180-days long cultures of fetal brain tissue four types of cells could be distinguished: 1. large, polygonal cells, 2. small, round, immature glia-cells, 3. bipolar spongioblasts, 4. gliant astrocytes. These types of cells could not be identified with the cell types of adult human brain culture, but similar types of cells were found in cultures prepared of gliomas of different degree of malignancy. There is some evidence to suggest, that among these types of cells the most important are immature glial cells, since they seem to be multipotent and may play a part in the gliogenesis and in the formation of gliomas as well.", "contents": "[Similarities between cultured human fetal glia cells and cell types from gliomas; cell culture studies]. Authors carried out a comparative study of cell-cultures of human fetal brain tissue and gliomas of various histological structures. In 180-days long cultures of fetal brain tissue four types of cells could be distinguished: 1. large, polygonal cells, 2. small, round, immature glia-cells, 3. bipolar spongioblasts, 4. gliant astrocytes. These types of cells could not be identified with the cell types of adult human brain culture, but similar types of cells were found in cultures prepared of gliomas of different degree of malignancy. There is some evidence to suggest, that among these types of cells the most important are immature glial cells, since they seem to be multipotent and may play a part in the gliogenesis and in the formation of gliomas as well."}
{"id": "PMID:219325", "title": "[Study of ganglioside therapy in maxillofacial surgery].", "content": "56 patients have been treated with cerebral gangliosides by the Authors. They underwent a maxillo-facial operation due to various pathological reasons (traumas, tumors, malformations). They presented secondary symptoms such as neurological deficits of the V and VII paired cranial nerves. The recovery from neurological sensitive, motor deficit have been positive, and the Authors have been encouraged to the therapeutical use of gangliosides in the mentioned pathology and to a wider experiment of the test product.", "contents": "[Study of ganglioside therapy in maxillofacial surgery]. 56 patients have been treated with cerebral gangliosides by the Authors. They underwent a maxillo-facial operation due to various pathological reasons (traumas, tumors, malformations). They presented secondary symptoms such as neurological deficits of the V and VII paired cranial nerves. The recovery from neurological sensitive, motor deficit have been positive, and the Authors have been encouraged to the therapeutical use of gangliosides in the mentioned pathology and to a wider experiment of the test product."}
{"id": "PMID:219330", "title": "[Development of ossification centers in childhood. A supplement to diagnosis and therapy (author's transl)].", "content": "The development of ossification centers in the region of the knee, the head of the femur, in the hand and the ossification of the iliac apophyses is of great significance in childhood. Timely or delayed appearance of the distal femoral and proximal tibial epiphyseal centers is an aid to confirming the diagnosis of a neonatal hypothyrosis. The normal range of variation of the appearance of the center in the head of the femur is therefore important to avoid unnecessary treatment when other parameters of hip dysplasia are lacking. Excessive growth in length, prospective calculation in differences in leg length and therapeutic measures for scoliosis are indications for the determination of the bone age.", "contents": "[Development of ossification centers in childhood. A supplement to diagnosis and therapy (author's transl)]. The development of ossification centers in the region of the knee, the head of the femur, in the hand and the ossification of the iliac apophyses is of great significance in childhood. Timely or delayed appearance of the distal femoral and proximal tibial epiphyseal centers is an aid to confirming the diagnosis of a neonatal hypothyrosis. The normal range of variation of the appearance of the center in the head of the femur is therefore important to avoid unnecessary treatment when other parameters of hip dysplasia are lacking. Excessive growth in length, prospective calculation in differences in leg length and therapeutic measures for scoliosis are indications for the determination of the bone age."}
{"id": "PMID:219339", "title": "Defective initiation of oxidative metabolism in polymorphonuclear leukocytes.", "content": "The polymorphonuclear leukocytes of a two-year-old boy who had multiple episodes of bacterial infections demonstrated defective oxidative metabolism with phagocytic, but not with soluble (non-phagocytic), metabolic stimuli. We used a chemiluminescence assay to examine the patient's polymorphonuclear leukocyte responses to numerous particulate and soluble stimuli. The patient's polymorphonuclear leukocytes had substantially depressed chemiluminescent responses during phagocytosis of opsonized particles (latex, pneumococci, pseudomonas, streptococci and zymosan); however, we observed normal chemiluminescent responses when these leukocytes were stimulated with soluble agents (sodium fluoride, concanavalin A, cytochalasin E, calcium ionophore A23187 or phorbol myristate acetate). Polymorphonuclear leukocyte oxygen consumption and superoxide production were impaired during phagocytosis, even though phagocytosis was normal. In addition to the metabolic defect, this patient's polymorphonuclear leukocytes had depressed chemotactic and bactericidal activities. This study provides evidence that polymorphonuclear leukocytes have more than one mechanism for initiating oxidative metabolism.", "contents": "Defective initiation of oxidative metabolism in polymorphonuclear leukocytes. The polymorphonuclear leukocytes of a two-year-old boy who had multiple episodes of bacterial infections demonstrated defective oxidative metabolism with phagocytic, but not with soluble (non-phagocytic), metabolic stimuli. We used a chemiluminescence assay to examine the patient's polymorphonuclear leukocyte responses to numerous particulate and soluble stimuli. The patient's polymorphonuclear leukocytes had substantially depressed chemiluminescent responses during phagocytosis of opsonized particles (latex, pneumococci, pseudomonas, streptococci and zymosan); however, we observed normal chemiluminescent responses when these leukocytes were stimulated with soluble agents (sodium fluoride, concanavalin A, cytochalasin E, calcium ionophore A23187 or phorbol myristate acetate). Polymorphonuclear leukocyte oxygen consumption and superoxide production were impaired during phagocytosis, even though phagocytosis was normal. In addition to the metabolic defect, this patient's polymorphonuclear leukocytes had depressed chemotactic and bactericidal activities. This study provides evidence that polymorphonuclear leukocytes have more than one mechanism for initiating oxidative metabolism."}
{"id": "PMID:219345", "title": "Isolation of a virus from the pancreas of a child with diabetic ketoacidosis.", "content": "A healthy 10-year-old boy was admitted to the hospital in diabetic ketoacidosis within three days of onset of symptoms of a flu-like illness. He died seven days later and post-mortem examination showed lymphocytic infiltration of the islets of Langerhans and necrosis of beta cells. Inoculation of mouse, monkey and human cell cultures with homogenates from the patient's pancreas led to isolation of a virus. Serologic studies revealed a rise in the titer of neutralizing antibody to this virus from less than 4 on the second hospital day to 32 on the day of death. Neutralization data showed that the virus was related to a diabetogenic variant derived from Coxsackievirus B4. Inoculation of mice with the human isolate produced hyperglycemia, inflammatory cells in the islets of Langerhans and beta-cell necrosis. Staining of mouse pancreatic sections with fluorescein-labeled antiviral antibody revealed viral antigens in beta cells. Both the clinical picture and animal studies suggested that the patient's diabetes was virus induced.", "contents": "Isolation of a virus from the pancreas of a child with diabetic ketoacidosis. A healthy 10-year-old boy was admitted to the hospital in diabetic ketoacidosis within three days of onset of symptoms of a flu-like illness. He died seven days later and post-mortem examination showed lymphocytic infiltration of the islets of Langerhans and necrosis of beta cells. Inoculation of mouse, monkey and human cell cultures with homogenates from the patient's pancreas led to isolation of a virus. Serologic studies revealed a rise in the titer of neutralizing antibody to this virus from less than 4 on the second hospital day to 32 on the day of death. Neutralization data showed that the virus was related to a diabetogenic variant derived from Coxsackievirus B4. Inoculation of mice with the human isolate produced hyperglycemia, inflammatory cells in the islets of Langerhans and beta-cell necrosis. Staining of mouse pancreatic sections with fluorescein-labeled antiviral antibody revealed viral antigens in beta cells. Both the clinical picture and animal studies suggested that the patient's diabetes was virus induced."}
{"id": "PMID:219348", "title": "[Behavior of certain parameters of lipid and energy metabolism. 5. Effects of high-fat and low-fat diets on certain biochemical parameters in rat livers before and after change of diet].", "content": "Typical metabolic patterns are detectable in the livers of growing rats after feeding diets with high (25%) or low (2%) fat contents. In view of the elucidation of problems related to the regulation of the metabolic processes, it is of interest to know in what way these metabolic patterns change after short-time change from the one diet to the other and if there are hierarchies. Within 2 days after change of diet, the enzymes glucose-6-phosphate dehydrogenase, NAD-malate dehydrogenase, lactate dehydrogenase, citrate synthase and fatty acid synthase were affected, only the 3'.5'-c AMP-splitting phosphodieterase showed no change. The metabolites lactate and pyruvate also changed, inversely to lactate dehydrogenase activity, the lactate-pyruvate ratio remaining almost constant. Acetyl CoA also responded in a characteristic manner. The single parameters were differently affected by the kind of the change of diet (from high-fat to low-fat diet or inversely). For example, glucose-6-phosphate dehydrogenase responded very rapidly to the change from the high-fat to the low-fat diet, malate dehydrogenase behaved inversely, and citrate synthase responded to both changes. Consequently, the regulatory processes after change of diet start from different sides. It is thinkable that this behaviour is related to the different roles of the determined parameters in fat and energy metabolism.", "contents": "[Behavior of certain parameters of lipid and energy metabolism. 5. Effects of high-fat and low-fat diets on certain biochemical parameters in rat livers before and after change of diet]. Typical metabolic patterns are detectable in the livers of growing rats after feeding diets with high (25%) or low (2%) fat contents. In view of the elucidation of problems related to the regulation of the metabolic processes, it is of interest to know in what way these metabolic patterns change after short-time change from the one diet to the other and if there are hierarchies. Within 2 days after change of diet, the enzymes glucose-6-phosphate dehydrogenase, NAD-malate dehydrogenase, lactate dehydrogenase, citrate synthase and fatty acid synthase were affected, only the 3'.5'-c AMP-splitting phosphodieterase showed no change. The metabolites lactate and pyruvate also changed, inversely to lactate dehydrogenase activity, the lactate-pyruvate ratio remaining almost constant. Acetyl CoA also responded in a characteristic manner. The single parameters were differently affected by the kind of the change of diet (from high-fat to low-fat diet or inversely). For example, glucose-6-phosphate dehydrogenase responded very rapidly to the change from the high-fat to the low-fat diet, malate dehydrogenase behaved inversely, and citrate synthase responded to both changes. Consequently, the regulatory processes after change of diet start from different sides. It is thinkable that this behaviour is related to the different roles of the determined parameters in fat and energy metabolism."}
{"id": "PMID:219349", "title": "Control of cellular proliferation by the fibroblast and epidermal growth factors.", "content": "Recent studies on the effect of the fibroblast and epidermal growth factors (FGF and EGF, respectively) on the proliferation of ovarian cells and vascular endothelial cells are reviewed. During the ovarian cycle, luteal cells are derived from granulosa cells by a process of cytomorphosis. These two cell types thus allow a study of the changes that occur in growth control when one cell type is converted into another. Also described is the control of vascular endothelial cell proliferation by FGF (but not by EGF). We discuss the effects of FGF and EGF on cells derived from the embryonic ectoderm, mesoderm, and endoderm and examine the hypothesis that cellular specificity for various growth factors is conferred during embryo development. Finally, since antagonists of growth factors are probably as important as the mitogens in the overall control of cell proliferation, we review certain mechanisms and agents through which the mitogenic effect of FGF can be repressed, i.e., cell-cell interaction at confluence, trophic hormones, and a diffusible factor(s) from cartilage.", "contents": "Control of cellular proliferation by the fibroblast and epidermal growth factors. Recent studies on the effect of the fibroblast and epidermal growth factors (FGF and EGF, respectively) on the proliferation of ovarian cells and vascular endothelial cells are reviewed. During the ovarian cycle, luteal cells are derived from granulosa cells by a process of cytomorphosis. These two cell types thus allow a study of the changes that occur in growth control when one cell type is converted into another. Also described is the control of vascular endothelial cell proliferation by FGF (but not by EGF). We discuss the effects of FGF and EGF on cells derived from the embryonic ectoderm, mesoderm, and endoderm and examine the hypothesis that cellular specificity for various growth factors is conferred during embryo development. Finally, since antagonists of growth factors are probably as important as the mitogens in the overall control of cell proliferation, we review certain mechanisms and agents through which the mitogenic effect of FGF can be repressed, i.e., cell-cell interaction at confluence, trophic hormones, and a diffusible factor(s) from cartilage."}
{"id": "PMID:219350", "title": "Why cell biologists should be aware of genetically transmitted viruses.", "content": "Retrovirus genomes exist as endogenous genetic elements in the cells of many species used in biomedical research. Many cell lines spontaneously release virus, and other cells are induced to do so by procedures commonly used in research laboratories. The expression of endogenous retroviruses can affect the results of seemingly unrelated experiments. Some retroviruses endogenous to animals grow avidly in human cells. They are not known to be hazardous to man, but further studies are necessary.", "contents": "Why cell biologists should be aware of genetically transmitted viruses. Retrovirus genomes exist as endogenous genetic elements in the cells of many species used in biomedical research. Many cell lines spontaneously release virus, and other cells are induced to do so by procedures commonly used in research laboratories. The expression of endogenous retroviruses can affect the results of seemingly unrelated experiments. Some retroviruses endogenous to animals grow avidly in human cells. They are not known to be hazardous to man, but further studies are necessary."}
{"id": "PMID:219351", "title": "Genetic control of mouse leukemia virus replication.", "content": "The Fv-1 gene of the mouse is a cellular gene, which prevents the replication of murine leukemia viruses. We investigated its intracellular site of action and found that the Fv-1 gene product blocks the appearance of virus-specific RNA in nonpermissive cells, which suggested a transcriptional or a preintegration block. Experiments performed to distinguish between these two possibilities revealed that the Fv-I gene restriction prevents integration of the reverse transcribed proviral DNA into the cell genome. However, we also found that the levels of unintegrated proviral DNA were not significantly affected by the Fv-1 gene restriction soon after infection. These data show that the Fv-1 gene product inhibits a step of the virus life cycle after the synthesis of proviral DNA but before its integration.", "contents": "Genetic control of mouse leukemia virus replication. The Fv-1 gene of the mouse is a cellular gene, which prevents the replication of murine leukemia viruses. We investigated its intracellular site of action and found that the Fv-1 gene product blocks the appearance of virus-specific RNA in nonpermissive cells, which suggested a transcriptional or a preintegration block. Experiments performed to distinguish between these two possibilities revealed that the Fv-I gene restriction prevents integration of the reverse transcribed proviral DNA into the cell genome. However, we also found that the levels of unintegrated proviral DNA were not significantly affected by the Fv-1 gene restriction soon after infection. These data show that the Fv-1 gene product inhibits a step of the virus life cycle after the synthesis of proviral DNA but before its integration."}
{"id": "PMID:219352", "title": "RNA tumor virus genes and the transforming genes: genetic transmission, infectious spread, and modes of expression.", "content": "The genetic conservation and evolution of virogenes in mammalian species are described in relation to the horizontal, vertical, and congenital transmission of type C RNA oncogenic viruses within members of a given species, or among members of near and/or distantly related species. Examples of oncogenic virus infection between ancestors of the mouse, cat, pig, and primates as well as the integration of the virus into the host's genome are documented. The possible normal functions of the virogenes as a part of the cellular genome of many species are explored. Recent evidence of genetic recombination (genetic mixing) among distinct type C viruses is also reviewed, thus completing an overview of the evolutionary past, present, and complex future relationships of oncogenic RNA viruses and mammalian species.", "contents": "RNA tumor virus genes and the transforming genes: genetic transmission, infectious spread, and modes of expression. The genetic conservation and evolution of virogenes in mammalian species are described in relation to the horizontal, vertical, and congenital transmission of type C RNA oncogenic viruses within members of a given species, or among members of near and/or distantly related species. Examples of oncogenic virus infection between ancestors of the mouse, cat, pig, and primates as well as the integration of the virus into the host's genome are documented. The possible normal functions of the virogenes as a part of the cellular genome of many species are explored. Recent evidence of genetic recombination (genetic mixing) among distinct type C viruses is also reviewed, thus completing an overview of the evolutionary past, present, and complex future relationships of oncogenic RNA viruses and mammalian species."}
{"id": "PMID:219353", "title": "Eukaryotic gene regulation studies with mouse mammary tumor virus in tissue culture cells.", "content": "The transcriptional regulation of mouse mammary tumor virus has been investigated in cell culture systems. These systems offer several insights into mechanisms of gene control including tenfold stimulation by glucocorticoids and spontaneous alterations in levels of constitutive transcription.", "contents": "Eukaryotic gene regulation studies with mouse mammary tumor virus in tissue culture cells. The transcriptional regulation of mouse mammary tumor virus has been investigated in cell culture systems. These systems offer several insights into mechanisms of gene control including tenfold stimulation by glucocorticoids and spontaneous alterations in levels of constitutive transcription."}
{"id": "PMID:219354", "title": "Genesis of a virus-transforming gene.", "content": "The gene src responsible for neoplastic transformation of fibroblasts by avian sarcoma viruses was apparently derived from highly conserved nucleotide sequences in the normal avian genome. The cellular homologue of src is unlinked to the genome of an endogenous virus in chicken cells and functions in an unknown manner during normal cell metabolism.", "contents": "Genesis of a virus-transforming gene. The gene src responsible for neoplastic transformation of fibroblasts by avian sarcoma viruses was apparently derived from highly conserved nucleotide sequences in the normal avian genome. The cellular homologue of src is unlinked to the genome of an endogenous virus in chicken cells and functions in an unknown manner during normal cell metabolism."}
{"id": "PMID:219355", "title": "Transformation by viruses: simian virus 40 as a model system.", "content": "Simian virus 40 (SV40), a DNA-containing tumor virus in the papovavirus group, represents an ideal model system for the analysis of the mechanism of viral-induced tumorigenesis because of the small size of its genome and its broad range of oncogenic potential. Viral genes persist and are expressed in SV40-transformed cells. Temperature-sensitive (ts) mutants of the virus have proved to be valuable tools for the identification and analysis of viral gene expression in transformed cells. Through the use of such mutants, it has been determined that a specific gene product (A-protein) is required to initiate cellular transformation. The role of virus genes in the maintenance of the transformed state was determined by transformation of the cells of mouse, hamster, and human origin by ts virus containing A-gene mutations. These cells were then examined under permissive and nonpermissive conditions for the presence of a variety of intracellular and surface alterations commonly associated with neoplastic transformation. From the results of such experiments, it has been concluded that an SV40-specific function is also necessary for the maintenance of at least some of the phenotypic properties of the transformed state. Indirect evidence, derived from a comparison of the biological and biochemical properties of the SV40-induced tumor (T) antigen and the gene A-protein, supports the idea that T-antigen is a product of the A-gene. One model devised to explain the mechanism by which the gene A-protein might function as an effector of transformation is presented.", "contents": "Transformation by viruses: simian virus 40 as a model system. Simian virus 40 (SV40), a DNA-containing tumor virus in the papovavirus group, represents an ideal model system for the analysis of the mechanism of viral-induced tumorigenesis because of the small size of its genome and its broad range of oncogenic potential. Viral genes persist and are expressed in SV40-transformed cells. Temperature-sensitive (ts) mutants of the virus have proved to be valuable tools for the identification and analysis of viral gene expression in transformed cells. Through the use of such mutants, it has been determined that a specific gene product (A-protein) is required to initiate cellular transformation. The role of virus genes in the maintenance of the transformed state was determined by transformation of the cells of mouse, hamster, and human origin by ts virus containing A-gene mutations. These cells were then examined under permissive and nonpermissive conditions for the presence of a variety of intracellular and surface alterations commonly associated with neoplastic transformation. From the results of such experiments, it has been concluded that an SV40-specific function is also necessary for the maintenance of at least some of the phenotypic properties of the transformed state. Indirect evidence, derived from a comparison of the biological and biochemical properties of the SV40-induced tumor (T) antigen and the gene A-protein, supports the idea that T-antigen is a product of the A-gene. One model devised to explain the mechanism by which the gene A-protein might function as an effector of transformation is presented."}
{"id": "PMID:219356", "title": "Regulation of viral functions in simian virus 40-transformed cells.", "content": "To define the relationship between simian virus 40 (SV40)-specific T-antigen and cell growth and to look for regulatory mechanisms that might control T-antigen synthesis in transformed cells, we studied the expression of T-antigen and the viral transcription in SV40-transformed cells that were exponentially growing or arrested in the G1-phase of the cell cycle. We took advantage of the behavior of two lines of SV40-transformed mouse 3T3 cells (ts SV3T3), which, although transformed by wild-type SV40, are temperature sensitive for the expression of the transformed phenotype. At 32 degrees C, ts SV3T3 cells behave like standard transformants, whereas at 39 degrees C, they become arrested in G1 after reaching saturatio n density or under serum starvation. At 32 degrees C or growing at 39 degrees C, ts SV3T3 were 100% T-antigen positive and contained virus-specific mRNA. However, after G1 arrest at 39 degrees C, most of the cells became T-antigen negative. This seems to be caused by a lack of transcription of the integrated viral DNA, since these cells contain no appreciable amounts of SV40-specific RNA. Induction of proliferation in resting, T-antigen-negative ts SV3T3 cultures results in the reappearance of T-antigen a few hours before the cells enter DNA synthesis. These results suggest that transcription of the viral genome and T-antigen expression in SV40-transformed cells is subjected to a cell cycle control.", "contents": "Regulation of viral functions in simian virus 40-transformed cells. To define the relationship between simian virus 40 (SV40)-specific T-antigen and cell growth and to look for regulatory mechanisms that might control T-antigen synthesis in transformed cells, we studied the expression of T-antigen and the viral transcription in SV40-transformed cells that were exponentially growing or arrested in the G1-phase of the cell cycle. We took advantage of the behavior of two lines of SV40-transformed mouse 3T3 cells (ts SV3T3), which, although transformed by wild-type SV40, are temperature sensitive for the expression of the transformed phenotype. At 32 degrees C, ts SV3T3 cells behave like standard transformants, whereas at 39 degrees C, they become arrested in G1 after reaching saturatio n density or under serum starvation. At 32 degrees C or growing at 39 degrees C, ts SV3T3 were 100% T-antigen positive and contained virus-specific mRNA. However, after G1 arrest at 39 degrees C, most of the cells became T-antigen negative. This seems to be caused by a lack of transcription of the integrated viral DNA, since these cells contain no appreciable amounts of SV40-specific RNA. Induction of proliferation in resting, T-antigen-negative ts SV3T3 cultures results in the reappearance of T-antigen a few hours before the cells enter DNA synthesis. These results suggest that transcription of the viral genome and T-antigen expression in SV40-transformed cells is subjected to a cell cycle control."}
{"id": "PMID:219357", "title": "The actions of hormones on adenylate cyclase systems.", "content": "The glucagon-sensitive adenylate cyclase system, viewed from the perspective of its behavior with isolated membrane preparations, displays far more complex regulatory characteristics than could have been envisioned from its behavior in the intact cell. What has emerged from our studies with isolated hepatic membranes is that glucagon can exert at least three actions which we believe are interdependent: desentization of the receptor, activation of adenylate cyclase, and promotion of adenosine inhibition of adenylate cyclase activity. Although the molecular basis remains unknown, GTP is intimately involved in the three processes. Undoubtedly, further levels of complexity will develop when the enzyme system is dissected and its components become amenable to study at the molecular level. At the moment, it is clear that adenylate cyclase systems are provided with a plethora of regulatory processes for controlling cyclic AMP production both in the absence and presence of hormones.", "contents": "The actions of hormones on adenylate cyclase systems. The glucagon-sensitive adenylate cyclase system, viewed from the perspective of its behavior with isolated membrane preparations, displays far more complex regulatory characteristics than could have been envisioned from its behavior in the intact cell. What has emerged from our studies with isolated hepatic membranes is that glucagon can exert at least three actions which we believe are interdependent: desentization of the receptor, activation of adenylate cyclase, and promotion of adenosine inhibition of adenylate cyclase activity. Although the molecular basis remains unknown, GTP is intimately involved in the three processes. Undoubtedly, further levels of complexity will develop when the enzyme system is dissected and its components become amenable to study at the molecular level. At the moment, it is clear that adenylate cyclase systems are provided with a plethora of regulatory processes for controlling cyclic AMP production both in the absence and presence of hormones."}
{"id": "PMID:219358", "title": "Reconstruction of cells by Sendai virus-induced fusion of cell fragments.", "content": "Large numbers of animal cells can be enucleated by centrifugation in the presence of cytochalasin. The nuclei (minicells) obtained by this technique are surrounded by a thin rim of cytoplasm and a cell membrane. The cytoplasms (anucleate cells) contain cytoplasmic organelles and are capable of protein synthesis. By themselves, these cell fragments are not viable under usual culture conditions for longer than 2 days after enucleation. They can, however, be fused by UV-inactivated Sendai virus to form reconstituted cells. Nuclei from rat myoblasts have been combined with cytoplasms from mouse fibroblasts. The resulting reconstituted cells are viable and multiply rapidly in vitro. Enucleation or disruption of \"micronucleated\" cells, cells in which the genome has been fragmented into many small micronuclei by prolonged exposure to antimitotic agents results in microcells. These cell fragments are subdiploid and may contain as little as a single chromosome. Fusion of microcells from normal cells with intact mutant cells offers a method of transferring complementing chromosomes into genetically defective cells. Specific areas in which reconstitution techniques should prove useful include studies of gene expression, cell differentiation, and the dependence of mitochondria on nuclear genes. Microcell hybrids could be useful in chromosome mapping and gene complementation analysis.", "contents": "Reconstruction of cells by Sendai virus-induced fusion of cell fragments. Large numbers of animal cells can be enucleated by centrifugation in the presence of cytochalasin. The nuclei (minicells) obtained by this technique are surrounded by a thin rim of cytoplasm and a cell membrane. The cytoplasms (anucleate cells) contain cytoplasmic organelles and are capable of protein synthesis. By themselves, these cell fragments are not viable under usual culture conditions for longer than 2 days after enucleation. They can, however, be fused by UV-inactivated Sendai virus to form reconstituted cells. Nuclei from rat myoblasts have been combined with cytoplasms from mouse fibroblasts. The resulting reconstituted cells are viable and multiply rapidly in vitro. Enucleation or disruption of \"micronucleated\" cells, cells in which the genome has been fragmented into many small micronuclei by prolonged exposure to antimitotic agents results in microcells. These cell fragments are subdiploid and may contain as little as a single chromosome. Fusion of microcells from normal cells with intact mutant cells offers a method of transferring complementing chromosomes into genetically defective cells. Specific areas in which reconstitution techniques should prove useful include studies of gene expression, cell differentiation, and the dependence of mitochondria on nuclear genes. Microcell hybrids could be useful in chromosome mapping and gene complementation analysis."}
{"id": "PMID:219359", "title": "Immunoglobulin production by lymphosarcomas induced by Abelson virus in mice.", "content": "A brief review of the origin and tumor-inducing properties of Abelson murine leukemia virus is given. The most common neoplasm induced by this virus in vivo is a nonthymic lymphocytic tumor of bone marrow and lymph node origin. Two morphologic types of lymphosarcomas are the undifferentiated lymphosarcoma (LS) and the plasmacytic lymphosarcoma (PL). With the electron microscope, both tumor cell types may be mixed and contain undifferentiated cells or cells with a moderate amount of rough endoplasmic reticulum and polysomes. PL tumors are composed predominantly of the latter. In biosynthetic studies, PL tumors produce more immunoglobulin (Ig) than LS and more of the Ig-heavy chain, which is thought to be the murine counterpart of IgD. PL-cells sensitized with rabbit antisera to mouse kappa chains formed rosettes with formalinized protein-A producing Staphylococcus aureus Cowan I strain. The rabbit antisera were specific for kappa chains by absorption. The failure of lymphosarcoma cells to secrete Ig indicates their differentiation is blocked by the transformation process. Lymphosarcoma cells appear then to be derived from B-lymphocytes.", "contents": "Immunoglobulin production by lymphosarcomas induced by Abelson virus in mice. A brief review of the origin and tumor-inducing properties of Abelson murine leukemia virus is given. The most common neoplasm induced by this virus in vivo is a nonthymic lymphocytic tumor of bone marrow and lymph node origin. Two morphologic types of lymphosarcomas are the undifferentiated lymphosarcoma (LS) and the plasmacytic lymphosarcoma (PL). With the electron microscope, both tumor cell types may be mixed and contain undifferentiated cells or cells with a moderate amount of rough endoplasmic reticulum and polysomes. PL tumors are composed predominantly of the latter. In biosynthetic studies, PL tumors produce more immunoglobulin (Ig) than LS and more of the Ig-heavy chain, which is thought to be the murine counterpart of IgD. PL-cells sensitized with rabbit antisera to mouse kappa chains formed rosettes with formalinized protein-A producing Staphylococcus aureus Cowan I strain. The rabbit antisera were specific for kappa chains by absorption. The failure of lymphosarcoma cells to secrete Ig indicates their differentiation is blocked by the transformation process. Lymphosarcoma cells appear then to be derived from B-lymphocytes."}
{"id": "PMID:219360", "title": "Studies on synapse formation and opiate dependence.", "content": "Neuroblastoma x glioma in NG108-15 cells possess opiate, alpha-adrenergic, and muscarinic acetylcholine receptors, which mediate an inhibition of adenylate cyclase. Growth of cells for 12--48 hours in the presence of a receptor--activator gradually results in a compensatory increase in adenylate cyclase activity. Withdrawal of the receptor ligand then results in relatively long-lived increases in adenylate cyclase activity and intracellular cAMP levels. Thus cells grown in the presence of morphine, norepinephrine, or acetylcholine seem to become dependent on the compound to maintain normal cAMP levels.", "contents": "Studies on synapse formation and opiate dependence. Neuroblastoma x glioma in NG108-15 cells possess opiate, alpha-adrenergic, and muscarinic acetylcholine receptors, which mediate an inhibition of adenylate cyclase. Growth of cells for 12--48 hours in the presence of a receptor--activator gradually results in a compensatory increase in adenylate cyclase activity. Withdrawal of the receptor ligand then results in relatively long-lived increases in adenylate cyclase activity and intracellular cAMP levels. Thus cells grown in the presence of morphine, norepinephrine, or acetylcholine seem to become dependent on the compound to maintain normal cAMP levels."}
{"id": "PMID:219362", "title": "Mouse lymphoma cells with mutations of cyclic AMP-dependent protein kinase.", "content": "Because S49 cells are senstivie to killing by cyclic AMP (cAMP), mutants can be selected which have a variety of defects in their ability to generate or respond to cAMP. One class of mutants, that with deficiencies in cAMP-dependent protein kinase, has been extensively characterized genetically and biochemically.", "contents": "Mouse lymphoma cells with mutations of cyclic AMP-dependent protein kinase. Because S49 cells are senstivie to killing by cyclic AMP (cAMP), mutants can be selected which have a variety of defects in their ability to generate or respond to cAMP. One class of mutants, that with deficiencies in cAMP-dependent protein kinase, has been extensively characterized genetically and biochemically."}
{"id": "PMID:219363", "title": "Paradox of the dose response to polypeptide hormones.", "content": "Highest concentrations of follicle-stimulating hormone (FSH) are required to elicit maximal increases in cAMP formation by isolated Sertoli cells in culture, and progressively lower concentrations are required to increase three late responses maximally (estradiol synthesis from testosterone, DNA synthesis, and synthesis of androgen-binding protein, respectively). Identical dose-response curve relations are observed when cholera toxin is used as the stimulatory agent. Results do not rule out the possibility that cAMP could mediate the various responses of Sertoli cells to FSH.", "contents": "Paradox of the dose response to polypeptide hormones. Highest concentrations of follicle-stimulating hormone (FSH) are required to elicit maximal increases in cAMP formation by isolated Sertoli cells in culture, and progressively lower concentrations are required to increase three late responses maximally (estradiol synthesis from testosterone, DNA synthesis, and synthesis of androgen-binding protein, respectively). Identical dose-response curve relations are observed when cholera toxin is used as the stimulatory agent. Results do not rule out the possibility that cAMP could mediate the various responses of Sertoli cells to FSH."}
{"id": "PMID:219364", "title": "Resting-proliferative transition in cultured mammalian cells.", "content": "Cell lines established in culture have been tested for their ability to enter a resting state upon serum step-down. The reentry of resting cells into a proliferative state has been studied. This transition between states of resting and of proliferation is considered a manifestation in cell cultures of physiologic growth regulatory mechanisms. The regulatory effects of hormones and hormone-like peptide growth factors on the resting-proliferative transition are analyzed.", "contents": "Resting-proliferative transition in cultured mammalian cells. Cell lines established in culture have been tested for their ability to enter a resting state upon serum step-down. The reentry of resting cells into a proliferative state has been studied. This transition between states of resting and of proliferation is considered a manifestation in cell cultures of physiologic growth regulatory mechanisms. The regulatory effects of hormones and hormone-like peptide growth factors on the resting-proliferative transition are analyzed."}
{"id": "PMID:219365", "title": "Hepatocyte growth control: in vitro approach to problems of liver regeneration and function.", "content": "Primary monolayer fetal and adult rat hepatocyte culture systems, which are being used to help analyze in vivo mechanisms controlling liver regeneration, proliferation, and differentiation are described. With results from animal studies of normal or genetically altered rats subjected to partial hepatectomy, to chemical infusions, or to specific dietary deficiency regimens, an apparently complex growth regulatory pattern has emerged. The data suggest a working hypothesis postulating interactions among hormone, nutritional, lipoprotein, and novel nucleotide factors at multiple regulatory sites. These findings may provide some conceptual and experimental basis for future research regarding the development of hepatic cancer, as it may arise spontaneously or from exposure to environmental carcinogens.", "contents": "Hepatocyte growth control: in vitro approach to problems of liver regeneration and function. Primary monolayer fetal and adult rat hepatocyte culture systems, which are being used to help analyze in vivo mechanisms controlling liver regeneration, proliferation, and differentiation are described. With results from animal studies of normal or genetically altered rats subjected to partial hepatectomy, to chemical infusions, or to specific dietary deficiency regimens, an apparently complex growth regulatory pattern has emerged. The data suggest a working hypothesis postulating interactions among hormone, nutritional, lipoprotein, and novel nucleotide factors at multiple regulatory sites. These findings may provide some conceptual and experimental basis for future research regarding the development of hepatic cancer, as it may arise spontaneously or from exposure to environmental carcinogens."}
{"id": "PMID:219366", "title": "Preliminary studies of sera and urine from patients with bladder cancer.", "content": "Some preliminary observations may be helpful as we proceed with studies of the humoral and cellular reactions in body fluids. 1) In the reactions with TAA from primary bladder cancers and from bladder cancer cell lines, we must be aware of complexing when we study sera or tumors from patients with more invasive tumors. 2) Earlier stage patient sera can react to antigens present in urine but may not react with antigens present on tumor cells. These reactions are mainly related to cell sediments or partially insoluble material present in the urine; it is difficult to interpret these reactions in a controlled study. 3) Using sera from patients with different stages of bladder cancer, we can test normal bladder cell lines (e.g., HCV-29, which has no CF reactivity with sera from patients with bladder cancer) for comparison with the patterns of TAA present in cancer cell lines (e.g., RT-4 and T-24). 4) There is no relationship between HSV and bladder TCC. 5) Cytomegalovirus and its components are associated with normal or cancer-related cell and urine components. We can study differentiation of such antigens from TAA, which produce cell-mediated immune responses.", "contents": "Preliminary studies of sera and urine from patients with bladder cancer. Some preliminary observations may be helpful as we proceed with studies of the humoral and cellular reactions in body fluids. 1) In the reactions with TAA from primary bladder cancers and from bladder cancer cell lines, we must be aware of complexing when we study sera or tumors from patients with more invasive tumors. 2) Earlier stage patient sera can react to antigens present in urine but may not react with antigens present on tumor cells. These reactions are mainly related to cell sediments or partially insoluble material present in the urine; it is difficult to interpret these reactions in a controlled study. 3) Using sera from patients with different stages of bladder cancer, we can test normal bladder cell lines (e.g., HCV-29, which has no CF reactivity with sera from patients with bladder cancer) for comparison with the patterns of TAA present in cancer cell lines (e.g., RT-4 and T-24). 4) There is no relationship between HSV and bladder TCC. 5) Cytomegalovirus and its components are associated with normal or cancer-related cell and urine components. We can study differentiation of such antigens from TAA, which produce cell-mediated immune responses."}
{"id": "PMID:219377", "title": "Synaptic plasticity.", "content": "Synaptic plasticity is manifested by long-lasting changes in synaptic potency. Increased potency is of special importance in relation to the neural basis of memory. Even mild repetitive stimulation evokes large and prolonged potentiations of hippocampal synapses, as is revealed by electrical recording either in vivo or in vitro. More importantly there is a matching hypertrophy of the synaptic spines on the dendrites of hippocampal granule cells, as is shown by most convincing electronmicrographs. The increase is to about 40% some 2 h after a mild stimulation (900 impulses) and there was relatively little decline by 23 h. There is brief reference to the metabolic processes that could be involved in this plastic response.", "contents": "Synaptic plasticity. Synaptic plasticity is manifested by long-lasting changes in synaptic potency. Increased potency is of special importance in relation to the neural basis of memory. Even mild repetitive stimulation evokes large and prolonged potentiations of hippocampal synapses, as is revealed by electrical recording either in vivo or in vitro. More importantly there is a matching hypertrophy of the synaptic spines on the dendrites of hippocampal granule cells, as is shown by most convincing electronmicrographs. The increase is to about 40% some 2 h after a mild stimulation (900 impulses) and there was relatively little decline by 23 h. There is brief reference to the metabolic processes that could be involved in this plastic response."}
{"id": "PMID:219380", "title": "Investigations on the methods of clinical application of a soluble BCG fraction (F70) in lung cancer.", "content": "Several parameters for an optimal treatment scheme of a soluble BCG fraction (F70) were investigated. Among lung cancer patients treated with F70 a restricted selection was made of patients treated with small doses (5--10 U) every second or third month (sparing scheme) and of patients treated every month with sharply increasing doses up to tens of thousands units (aggressive scheme). It was found that the survival rate and the rate of marked X-ray regressions were higher in the former group. As it was previously established for lung cancer patients treated with living BCG, in the group of sparing scheme-treated patients the longest survival period pertained to patients treated once and patients treated twice or three times and an inverse correlation existed between the number of applications of F70 and the mean survival period. It was concluded that, as with living BCG, a sparing approach to the immunotherapy of lung cancer with F70 is to be preferred to an aggressive approach. Illustrative cases treated once, twice and three times are presented.", "contents": "Investigations on the methods of clinical application of a soluble BCG fraction (F70) in lung cancer. Several parameters for an optimal treatment scheme of a soluble BCG fraction (F70) were investigated. Among lung cancer patients treated with F70 a restricted selection was made of patients treated with small doses (5--10 U) every second or third month (sparing scheme) and of patients treated every month with sharply increasing doses up to tens of thousands units (aggressive scheme). It was found that the survival rate and the rate of marked X-ray regressions were higher in the former group. As it was previously established for lung cancer patients treated with living BCG, in the group of sparing scheme-treated patients the longest survival period pertained to patients treated once and patients treated twice or three times and an inverse correlation existed between the number of applications of F70 and the mean survival period. It was concluded that, as with living BCG, a sparing approach to the immunotherapy of lung cancer with F70 is to be preferred to an aggressive approach. Illustrative cases treated once, twice and three times are presented."}
{"id": "PMID:219381", "title": "Oncogenicity in newborn and adult Syrian hamsters of SV40 temperature-sensitive (ts) mutants.", "content": "Newborn and adult Syrian hamsters were injected with wild-type SV40 and its temperature-sensitive (ts) mutants A30, A209, A239, B201 and BC210. In contrast to wild-type SV40, ts A30, ts A 239 and ts BC210 were oncogenic in adult hamsters inducing tumors after almost the same latent period as wild type SV40 in newborns but in lower number of animals. Study of TSTA in some tumors (1 generation) induced in newborn and adult hamsters by wild type SV40 and its ts mutants (with the use of immunogenicity and immunosensitivity tests) revealed no significant difference among compared tumors: most of them were immunogenic and immunosensitive. In contrast hamster embryo cells in vitro transformed by SV40 ts A30, ts A239 and ts A209 mutants, studied at different passage levels were all immunoresistant during about 30 in vitro passages and in most cases 10--100 times less immunogenic than hamster embryo cells in vitro transformed by wild type SV40. At higher passage level in some of these lines expression of TSTA improved. The data obtained are discussed in connection with the recently demonstrated [5] significant quantitative difference in tumor specific transplantation antigen activity in hamster cells in vivo and vitro infected, or transformed by wild type SV40 and its ts A mutants.", "contents": "Oncogenicity in newborn and adult Syrian hamsters of SV40 temperature-sensitive (ts) mutants. Newborn and adult Syrian hamsters were injected with wild-type SV40 and its temperature-sensitive (ts) mutants A30, A209, A239, B201 and BC210. In contrast to wild-type SV40, ts A30, ts A 239 and ts BC210 were oncogenic in adult hamsters inducing tumors after almost the same latent period as wild type SV40 in newborns but in lower number of animals. Study of TSTA in some tumors (1 generation) induced in newborn and adult hamsters by wild type SV40 and its ts mutants (with the use of immunogenicity and immunosensitivity tests) revealed no significant difference among compared tumors: most of them were immunogenic and immunosensitive. In contrast hamster embryo cells in vitro transformed by SV40 ts A30, ts A239 and ts A209 mutants, studied at different passage levels were all immunoresistant during about 30 in vitro passages and in most cases 10--100 times less immunogenic than hamster embryo cells in vitro transformed by wild type SV40. At higher passage level in some of these lines expression of TSTA improved. The data obtained are discussed in connection with the recently demonstrated [5] significant quantitative difference in tumor specific transplantation antigen activity in hamster cells in vivo and vitro infected, or transformed by wild type SV40 and its ts A mutants."}
{"id": "PMID:219383", "title": "Action of gonadotropin-releasing hormone and its superactive analogues on the anterior pituitary: the mechanism of release and synthesis of gonadotropins.", "content": "The role of prostaglandins (PG), their active intermediates or the adenylcyclase-cyclic AMP system for gonadotropin release and/or synthesis was evaluated by administering gonadotropin-releasing hormone (Gn-RH) and its superactive analog to normal and aspirin-treated rats. Serum LH levels, anterior pituitary malondialdehyde (MDA) content and cyclic AMP (cAMP) levels were followed. The pituitaries stimulated with Gn-RH or its superactive analog yielded more MDA and cAMP than the controls. Stimulation of the pituitary with the releasing hormones, after aspirin treatment, yielded 40--70% less MDA and lower LH values than the nontreated animals. The cAMP levels were not significantly lowered by the aspirin treatment. These studies suggest that the activation of the PG biosynthesis and the adenyl-cyclase-cyclic AMP system are not sequential but 2 separate physiological events. The active PG intermediates may only be responsible for the release of LH. It is not clear whether the activation of cAMP initiates also the processes preparatory to the synthesis of LH in the endoplasmic reticulum. In vivo studies in rats showed that the analogs (I and II) were 30 times more potent and had a more prolonged action on the pituitary (3 h) than Gn-RH. Ultrastructural studies on the anterior pituitary after hypophyseal stalk portal vessel infusion of Gn-RH and the analog (I and II) provided ample morphological evidence for both Gn-RH and analog induced gonadotropin-release and synthesis. The prolonged action of the superactive analog (I and II) on the gonadotrophs was also indicated by ultrastructural studies.", "contents": "Action of gonadotropin-releasing hormone and its superactive analogues on the anterior pituitary: the mechanism of release and synthesis of gonadotropins. The role of prostaglandins (PG), their active intermediates or the adenylcyclase-cyclic AMP system for gonadotropin release and/or synthesis was evaluated by administering gonadotropin-releasing hormone (Gn-RH) and its superactive analog to normal and aspirin-treated rats. Serum LH levels, anterior pituitary malondialdehyde (MDA) content and cyclic AMP (cAMP) levels were followed. The pituitaries stimulated with Gn-RH or its superactive analog yielded more MDA and cAMP than the controls. Stimulation of the pituitary with the releasing hormones, after aspirin treatment, yielded 40--70% less MDA and lower LH values than the nontreated animals. The cAMP levels were not significantly lowered by the aspirin treatment. These studies suggest that the activation of the PG biosynthesis and the adenyl-cyclase-cyclic AMP system are not sequential but 2 separate physiological events. The active PG intermediates may only be responsible for the release of LH. It is not clear whether the activation of cAMP initiates also the processes preparatory to the synthesis of LH in the endoplasmic reticulum. In vivo studies in rats showed that the analogs (I and II) were 30 times more potent and had a more prolonged action on the pituitary (3 h) than Gn-RH. Ultrastructural studies on the anterior pituitary after hypophyseal stalk portal vessel infusion of Gn-RH and the analog (I and II) provided ample morphological evidence for both Gn-RH and analog induced gonadotropin-release and synthesis. The prolonged action of the superactive analog (I and II) on the gonadotrophs was also indicated by ultrastructural studies."}
{"id": "PMID:219382", "title": "Peripheral nervous system in a case of canine giant axonal neuropathy.", "content": "The pathology of the peripheral nerves in a dog with naturally occurring giant axonal neuropathy (GAN) is described. Axonal swellings were found predominantly in the distal portions of the tibial and recurrent laryngeal nerves. Excess neurofilaments, often arranged in whorls, were present in the swellings which were found in both myelinated and non-myelinated fibres. Other axonal organelles tended to be isolated in small pockets and on occasions adaxonal Schwann cell processes partially separated these organelles from the axoplasm. The myelin sheath was attenuated over the swellings and short lengths of demyelinated axon were often seen adjacent to the enlargements. Some Schwann cells also contained excessive microfilaments. The peripheral nerve pathology in the dog appear closely similar to that of human GAN and to certain experimental toxic neuropathies, particularly those produced by n-hexane and methyl-butyl ketone.", "contents": "Peripheral nervous system in a case of canine giant axonal neuropathy. The pathology of the peripheral nerves in a dog with naturally occurring giant axonal neuropathy (GAN) is described. Axonal swellings were found predominantly in the distal portions of the tibial and recurrent laryngeal nerves. Excess neurofilaments, often arranged in whorls, were present in the swellings which were found in both myelinated and non-myelinated fibres. Other axonal organelles tended to be isolated in small pockets and on occasions adaxonal Schwann cell processes partially separated these organelles from the axoplasm. The myelin sheath was attenuated over the swellings and short lengths of demyelinated axon were often seen adjacent to the enlargements. Some Schwann cells also contained excessive microfilaments. The peripheral nerve pathology in the dog appear closely similar to that of human GAN and to certain experimental toxic neuropathies, particularly those produced by n-hexane and methyl-butyl ketone."}
{"id": "PMID:219388", "title": "Cord to cortex conduction in multiple sclerosis.", "content": "We studied 30 controls and 28 patients with multiple sclerosis (MS). M-waves, F-waves, and somatosensory responses evoked by median and peroneal nerve stimulation were used to estimate conduction times from the lumbar cord to the cortex; the cervical cord to the cortex; through the spinal cord; and in proximal segments of peripheral nerve. The central conduction times were significantly prolonged in the MS patients, giving an overall 79 percent incidence of abnormalities. Several patients who were asymptomatic in the tested arm (36 percent) or leg (16 percent) showed electrophysiologic abnormalities. By comparing conduction time from the lumbar cord to the cortex with the conduction time from the cervical cord to the cortex, the site of the lesion could be deduced, but not proven. The diagnostic yield from measuring the latencies of the somatosensory responses was 68 percent. We concluded that measuring central conduction times indirectly by use of M- and F-waves adds little to simple measurement of somatosensory responses.", "contents": "Cord to cortex conduction in multiple sclerosis. We studied 30 controls and 28 patients with multiple sclerosis (MS). M-waves, F-waves, and somatosensory responses evoked by median and peroneal nerve stimulation were used to estimate conduction times from the lumbar cord to the cortex; the cervical cord to the cortex; through the spinal cord; and in proximal segments of peripheral nerve. The central conduction times were significantly prolonged in the MS patients, giving an overall 79 percent incidence of abnormalities. Several patients who were asymptomatic in the tested arm (36 percent) or leg (16 percent) showed electrophysiologic abnormalities. By comparing conduction time from the lumbar cord to the cortex with the conduction time from the cervical cord to the cortex, the site of the lesion could be deduced, but not proven. The diagnostic yield from measuring the latencies of the somatosensory responses was 68 percent. We concluded that measuring central conduction times indirectly by use of M- and F-waves adds little to simple measurement of somatosensory responses."}
{"id": "PMID:219385", "title": "Characteristics of excitation and inhibition of the receptive fields of the retina and lateral geniculate body.", "content": "The process of excitation and inhibition in the receptive fields (RF) of the ganglion cells and lateral geniculate body (LGB) of the cat were examined. The extent of the dependence of the magnitude of excitation and inhibition in RF on stimulus intensity was determined. This dependence is a power function with power indices of 0.15--0.20 (LGB) and 0.3--0.5 (retina) for excitation and 0.2--0.3 (LGB) and 0.5--0.6 (retina) for inhibition.", "contents": "Characteristics of excitation and inhibition of the receptive fields of the retina and lateral geniculate body. The process of excitation and inhibition in the receptive fields (RF) of the ganglion cells and lateral geniculate body (LGB) of the cat were examined. The extent of the dependence of the magnitude of excitation and inhibition in RF on stimulus intensity was determined. This dependence is a power function with power indices of 0.15--0.20 (LGB) and 0.3--0.5 (retina) for excitation and 0.2--0.3 (LGB) and 0.5--0.6 (retina) for inhibition."}
{"id": "PMID:219389", "title": "Factors influencing the response of the cerebral circulation to phenylethylamine.", "content": "The cerebrovascular actions of phenylethylamine, an amine that has been implicated in the pathogenesis of migraine, were investigated in 16 anesthetized baboons. The influence of monoaminergic blocking agents and of a specific inhibitor of monoamine oxidase upon the cerebral circulatory and metabolic actions of phenylethylamine were examined. The reductions in cerebral blood flow (28 percent) and cerebral oxygen consumption (31 percent) that accompany the intracarotid administration of phenylethylamine (2 X 10(-6) moles per kilogram per minute) were unaffected by the prior administration of either phenoxybenzamine (1.5 mg per kilogram, IV) or pimozide (0.5 mg per kilogram, IV). The administration of phenoxybenzamine and pimozide per se did not significantly disturb cerebral blood flow or oxygen consumption. The ability of migraine patients to oxidatively deaminate phenylethylamine is reduced at the time of their attacks. In the present experiments, the administration of the monoamine oxidase type B inhibitor, deprenyl (1 mg per kilogram, IV), did not effect significant changes in cerebral blood flow or cerebral oxygen consumption. However, following deprenyl, the administration of phenylethylamine (4 X 10(-8) moles per kilogram per minute), a concentration which was without effect in normal animals, significantly reduced cerebral blood flow. Some of the possible mechanisms influencing the sensitivity of the cerebral circulation to phenylethylamine, and their relationship to migraine, are considered.", "contents": "Factors influencing the response of the cerebral circulation to phenylethylamine. The cerebrovascular actions of phenylethylamine, an amine that has been implicated in the pathogenesis of migraine, were investigated in 16 anesthetized baboons. The influence of monoaminergic blocking agents and of a specific inhibitor of monoamine oxidase upon the cerebral circulatory and metabolic actions of phenylethylamine were examined. The reductions in cerebral blood flow (28 percent) and cerebral oxygen consumption (31 percent) that accompany the intracarotid administration of phenylethylamine (2 X 10(-6) moles per kilogram per minute) were unaffected by the prior administration of either phenoxybenzamine (1.5 mg per kilogram, IV) or pimozide (0.5 mg per kilogram, IV). The administration of phenoxybenzamine and pimozide per se did not significantly disturb cerebral blood flow or oxygen consumption. The ability of migraine patients to oxidatively deaminate phenylethylamine is reduced at the time of their attacks. In the present experiments, the administration of the monoamine oxidase type B inhibitor, deprenyl (1 mg per kilogram, IV), did not effect significant changes in cerebral blood flow or cerebral oxygen consumption. However, following deprenyl, the administration of phenylethylamine (4 X 10(-8) moles per kilogram per minute), a concentration which was without effect in normal animals, significantly reduced cerebral blood flow. Some of the possible mechanisms influencing the sensitivity of the cerebral circulation to phenylethylamine, and their relationship to migraine, are considered."}
{"id": "PMID:219390", "title": "Glycine and experimental spinal spasticity.", "content": "Spasticity may result in part from segmental spinal disinhibition. We determined the content and specific activity of glycine (the putative neurotransmitter thought to mediate spinal postsynaptic inhibition) and serine (the probable precursor of glycine) in feline spastic spinal cord following the intra-aortic administration of two labelled precursors of glycine--14C-D-glucose and 14C-L-serine. The specific activities of both glycine and serine were significantly reduced in the ventromedial, central, and dorsal spinal gray matter in spastic animals. Glycine content remained at control values but serine content increased in spastic spinal cord. This study suggests that glycine turnover decreases in spasticity, owing to its diminished release, and supports neurophysiologic evidence of a decrement in postsynaptic inhibition.", "contents": "Glycine and experimental spinal spasticity. Spasticity may result in part from segmental spinal disinhibition. We determined the content and specific activity of glycine (the putative neurotransmitter thought to mediate spinal postsynaptic inhibition) and serine (the probable precursor of glycine) in feline spastic spinal cord following the intra-aortic administration of two labelled precursors of glycine--14C-D-glucose and 14C-L-serine. The specific activities of both glycine and serine were significantly reduced in the ventromedial, central, and dorsal spinal gray matter in spastic animals. Glycine content remained at control values but serine content increased in spastic spinal cord. This study suggests that glycine turnover decreases in spasticity, owing to its diminished release, and supports neurophysiologic evidence of a decrement in postsynaptic inhibition."}
{"id": "PMID:219391", "title": "The fine structure of blood cells in ceroid-lipofuscinosis (Spielmeyer-Vogt's disease).", "content": "Peripheral blood and bone marrow in a case of juvenile type of Spielmeyer-Vogt's disease were examined with the light and electron microscope for the occurrence of curvilinear profile (CLP), rectilinear profile (RLP), finger-print profile (FPP) and other inclusions. A large quantity of parallel tubular arrays (PTAs) and a few CLPs, RLPs and FPPs were present in the cytoplasm of the lymphocytes. In addition, many plasma cells in the bone marrow contained FPPs, RLPs and CLPs in the vacuoles of their cytoplasm. The other relevant inclusions were observed in the cytoplasm of the bone marrow cells. Moreover, amorphous or membranous inclusions with rectilinear or curvilinear profiles were seen in some vacuoles in the cytoplasm of many erythrocytes. The incidence of these characteristic inclusions in the plasma cells or the erythrocytes were not described nor the present. The correlation and the diagnostic significance of these characteristic inclusions were discussed.", "contents": "The fine structure of blood cells in ceroid-lipofuscinosis (Spielmeyer-Vogt's disease). Peripheral blood and bone marrow in a case of juvenile type of Spielmeyer-Vogt's disease were examined with the light and electron microscope for the occurrence of curvilinear profile (CLP), rectilinear profile (RLP), finger-print profile (FPP) and other inclusions. A large quantity of parallel tubular arrays (PTAs) and a few CLPs, RLPs and FPPs were present in the cytoplasm of the lymphocytes. In addition, many plasma cells in the bone marrow contained FPPs, RLPs and CLPs in the vacuoles of their cytoplasm. The other relevant inclusions were observed in the cytoplasm of the bone marrow cells. Moreover, amorphous or membranous inclusions with rectilinear or curvilinear profiles were seen in some vacuoles in the cytoplasm of many erythrocytes. The incidence of these characteristic inclusions in the plasma cells or the erythrocytes were not described nor the present. The correlation and the diagnostic significance of these characteristic inclusions were discussed."}
{"id": "PMID:219392", "title": "Neurocutaneous syndrome with excessive macrohydrocephalus. (Sturge-Weber/Klippel-Trenaunay syndrome).", "content": "2.5 years of follow-up of a boy with progressive macrohydrocephalus possibly as a consequence of an intracranial vascular malformation. There are prominent features of a Sturge-Weber as well as a Klippel-Trenaunary-syndrome.", "contents": "Neurocutaneous syndrome with excessive macrohydrocephalus. (Sturge-Weber/Klippel-Trenaunay syndrome). 2.5 years of follow-up of a boy with progressive macrohydrocephalus possibly as a consequence of an intracranial vascular malformation. There are prominent features of a Sturge-Weber as well as a Klippel-Trenaunary-syndrome."}
{"id": "PMID:219386", "title": "Spread of excitation along neuron chains of the frog tectum opticum in response to various visual stimuli.", "content": "The construction of \"chains of excitation\" based on latent periods of responses of silent neurons of the frog tectum opticum to repetitive visual stimuli revealed significant differences in the course of excitation of the neuronal structures during the action of simple (flashes) and complex (movement of a visual object) stimuli. Movement of excitation over tectal neurons is shown to be very complex in character, for whereas the excitation wave develops comparatively quickly in response to simple stimuli and narrowing of the pathway of excitation soon arises, in response to a stimulus of definite shape it lasts longer and the pathway of excitation remains comparatively constant in width for much longer.", "contents": "Spread of excitation along neuron chains of the frog tectum opticum in response to various visual stimuli. The construction of \"chains of excitation\" based on latent periods of responses of silent neurons of the frog tectum opticum to repetitive visual stimuli revealed significant differences in the course of excitation of the neuronal structures during the action of simple (flashes) and complex (movement of a visual object) stimuli. Movement of excitation over tectal neurons is shown to be very complex in character, for whereas the excitation wave develops comparatively quickly in response to simple stimuli and narrowing of the pathway of excitation soon arises, in response to a stimulus of definite shape it lasts longer and the pathway of excitation remains comparatively constant in width for much longer."}
{"id": "PMID:219394", "title": "[The effect of estrogens in the etiopathogenesis of endometrial adenocarcinoma].", "content": "Recent data suggesting that oestrogens also encourage the onset of adenocarcinoma of the endometrium in man are reviewed. Emphasis is placed on the fact that this is most likely to occur when prolonged oestrogeni stimulation is not suitably opposed by progesterone. It is felt that the latter, or its synthetic homologues, should be employed in all long-standing cases of exogenous or endogenous hyperoestrogenism.", "contents": "[The effect of estrogens in the etiopathogenesis of endometrial adenocarcinoma]. Recent data suggesting that oestrogens also encourage the onset of adenocarcinoma of the endometrium in man are reviewed. Emphasis is placed on the fact that this is most likely to occur when prolonged oestrogeni stimulation is not suitably opposed by progesterone. It is felt that the latter, or its synthetic homologues, should be employed in all long-standing cases of exogenous or endogenous hyperoestrogenism."}
{"id": "PMID:219399", "title": "[Blood transfusion and viral diseases. Recent acquisitions concerning viral hepatitis viruses, cytomegaloviruses and Epstein-Barr virus].", "content": "In recent years, an increasingly clear picture has been formed of the virus-induced syndromes that may follow a blood transfusion or the use of blood derivatives. Up to about 10 years ago, post-infusion infection was predominantly due to serum hepatitis. Blumberg's discovery of HBsAg (formerly known as Australia antigen) has made it possible to check and prevent viral hepatitis, type B, and to recognise such distinct forms as the mononucleosis-like syndrome caused by cytomegalic virus, infectious mononucleosis caused by EB virus, and so-called non A/non B hepatitis. A brief account of recent advances with respect to the biological features of the viruses responsible for type A and type B hepatitis, CMV and EB virus, and their behaviour in man is followed by an examination of the transfusional aspects, the methods used in their study, and the difficulties involved. The soundness of existing methods and the need for their standardisation are discussed.", "contents": "[Blood transfusion and viral diseases. Recent acquisitions concerning viral hepatitis viruses, cytomegaloviruses and Epstein-Barr virus]. In recent years, an increasingly clear picture has been formed of the virus-induced syndromes that may follow a blood transfusion or the use of blood derivatives. Up to about 10 years ago, post-infusion infection was predominantly due to serum hepatitis. Blumberg's discovery of HBsAg (formerly known as Australia antigen) has made it possible to check and prevent viral hepatitis, type B, and to recognise such distinct forms as the mononucleosis-like syndrome caused by cytomegalic virus, infectious mononucleosis caused by EB virus, and so-called non A/non B hepatitis. A brief account of recent advances with respect to the biological features of the viruses responsible for type A and type B hepatitis, CMV and EB virus, and their behaviour in man is followed by an examination of the transfusional aspects, the methods used in their study, and the difficulties involved. The soundness of existing methods and the need for their standardisation are discussed."}
{"id": "PMID:219400", "title": "Vasopressin modulates the activity of catecholamine containing neurons in specific brain regions.", "content": "Following the i.c.v. administration of antivasopressin serum the alpha-MPT-induced disappearance of noradrenaline was decreased in the dorsal septal nucleus, parafascicular nucleus and the rostral part of the nucleus tractus solitarii, whereas that of dopamine was lowered in the caudate nucleus and in the A2 region of the medulla oblongata. In general the effects are opposite to those previously found following the i.c.v. administration of vasopressin. The results support the hypothesis that vasopressin modulates catecholamine neurotransmission in specific brain regions of the rat.", "contents": "Vasopressin modulates the activity of catecholamine containing neurons in specific brain regions. Following the i.c.v. administration of antivasopressin serum the alpha-MPT-induced disappearance of noradrenaline was decreased in the dorsal septal nucleus, parafascicular nucleus and the rostral part of the nucleus tractus solitarii, whereas that of dopamine was lowered in the caudate nucleus and in the A2 region of the medulla oblongata. In general the effects are opposite to those previously found following the i.c.v. administration of vasopressin. The results support the hypothesis that vasopressin modulates catecholamine neurotransmission in specific brain regions of the rat."}
{"id": "PMID:219405", "title": "Focal odontodysgenesis of the maxillary second premolars in a child.", "content": "A few months before her sixth birthday, a Caucasian girl suffered progressively worse episodes of painful, nontender, erythematous swellings of the palate lingual to apparently healthy primary second molars. Neither of the developing maxillary second premolars was discerned clearly in radiographs, but, upon surgical exploration, incomplete crowns were found in both follicles. All the other premolars appeared to be developing normally. Histologic, histochemical, and chemical analyses showed that the enamel was hypocalcified, apparently as a result of hypomaturation; the dentin was essentially normal; and morphogenesis had ceased when the heights of contour of the crowns had not yet been reached. This pattern of developmental defects differs from those of well-characterized odontogenic disorders, such as regional odontodysplasia and amelogenesis imperfecta. We suggest that focal odontodysgenesis might be an appropriate term for it. The bilateral symmetry suggests a genetic component in the etiology.", "contents": "Focal odontodysgenesis of the maxillary second premolars in a child. A few months before her sixth birthday, a Caucasian girl suffered progressively worse episodes of painful, nontender, erythematous swellings of the palate lingual to apparently healthy primary second molars. Neither of the developing maxillary second premolars was discerned clearly in radiographs, but, upon surgical exploration, incomplete crowns were found in both follicles. All the other premolars appeared to be developing normally. Histologic, histochemical, and chemical analyses showed that the enamel was hypocalcified, apparently as a result of hypomaturation; the dentin was essentially normal; and morphogenesis had ceased when the heights of contour of the crowns had not yet been reached. This pattern of developmental defects differs from those of well-characterized odontogenic disorders, such as regional odontodysplasia and amelogenesis imperfecta. We suggest that focal odontodysgenesis might be an appropriate term for it. The bilateral symmetry suggests a genetic component in the etiology."}
{"id": "PMID:219410", "title": "Effect of polymyxin B sulfate on endotoxin activity in a gram-negative septicemia model.", "content": "The antiendotoxin effect of polymyxin B was investigated in experimentally induced septicemia in rabbits. The Pasteurella multocida organisms were sensitive to the antibacterial action of penicillin but not to polymyxin B. Animals pre-treated with polymyxin showed positive blood cultures and significantly reduced plasma endotoxin levels (Limulus test) with normal white blood cell and platelet counts when analyzed 6 hr after the injection of live organisms. Polymyxin therapy given after the animals had established septicemia-endotoxemia reduced the plasma endotoxin levels and improved the survival, but had no effect on the leukopenia and thrombocytopenia. The best survival data were obtained in rabbits who were treated with both penicillin and polymyxin. The data suggest that polymyxin is effective in neutralizing the endotoxic effects from live organisms and that the timing and perhaps duration of the polymyxin treatment is of critical importance. In addition, a modified Limulus lysate method was developed which showed that quantitative plasma endotoxin determination could be made more sensitive by prior heating of the plasma to remove the natural inhibitors.", "contents": "Effect of polymyxin B sulfate on endotoxin activity in a gram-negative septicemia model. The antiendotoxin effect of polymyxin B was investigated in experimentally induced septicemia in rabbits. The Pasteurella multocida organisms were sensitive to the antibacterial action of penicillin but not to polymyxin B. Animals pre-treated with polymyxin showed positive blood cultures and significantly reduced plasma endotoxin levels (Limulus test) with normal white blood cell and platelet counts when analyzed 6 hr after the injection of live organisms. Polymyxin therapy given after the animals had established septicemia-endotoxemia reduced the plasma endotoxin levels and improved the survival, but had no effect on the leukopenia and thrombocytopenia. The best survival data were obtained in rabbits who were treated with both penicillin and polymyxin. The data suggest that polymyxin is effective in neutralizing the endotoxic effects from live organisms and that the timing and perhaps duration of the polymyxin treatment is of critical importance. In addition, a modified Limulus lysate method was developed which showed that quantitative plasma endotoxin determination could be made more sensitive by prior heating of the plasma to remove the natural inhibitors."}
{"id": "PMID:219411", "title": "Pyruvate carboxylase deficiency and lactic acidosis in a retarded child without Leigh's disease.", "content": "A child with lactic acidosis, severe mental and developmental retardation, and proximal renal tubular acidosis is presented. Biopsy and autopsy studies show severe hepatic, renal cortical, and cerebral deficiencies in pyruvate carboxylase (EC 6.4.1.1) activity. The patient had 1.81 +/- 0.20 units/g fresh weight at biopsy and 0.75 +/- 0.07 units/g fresh weight hepatic pyruvate carboxylase activity at autopsy compared with 10.9, 11.3, and 9.5 units/g fresh weight in two autopsy and one biopsy controls, respectively. The patient's renal cortical pyruvate carboxylase activity at autopsy was 0.008 +/- 0.004 units/g fresh weight compared with 5.05 units/g in the autopsy control. The patient had no detectable (less than 0.018 units/g fresh weight) cerebral pyruvate carboxylase activity at autopsy compared with 0.44, 0.53, and 0.695 units/g in the autopsy cerebrum of one human and two rhesus monkeys, respectively. Pyruvate dehydrogenase complex, phosphoenolpyruvate carboxykinase (PEPCK, EC 4.1.1.32), and fructose-1,6-bisphosphatase (EC 3.1.3.11) activities were in the normal range. The patient's urine pH was above 7.9 when the total serum CO2 was greater than 7.8 mM. However, the patient was able to acidify the urine to pH 5.1 when the total serum CO2 was 1.6 mM. The neuropathologic examination of the brain at autopsy revealed no sign of Leigh's disease, although developmental and degenerative lesions were observed. This is the first reported patient with a primary deficiency in hepatic, renal, and cerebral pyruvate carboxylase deficiency in whom the neuropathologic lesions, distinct from those of Leigh's disease, and proximal renal tubular acidosis have both been documented.", "contents": "Pyruvate carboxylase deficiency and lactic acidosis in a retarded child without Leigh's disease. A child with lactic acidosis, severe mental and developmental retardation, and proximal renal tubular acidosis is presented. Biopsy and autopsy studies show severe hepatic, renal cortical, and cerebral deficiencies in pyruvate carboxylase (EC 6.4.1.1) activity. The patient had 1.81 +/- 0.20 units/g fresh weight at biopsy and 0.75 +/- 0.07 units/g fresh weight hepatic pyruvate carboxylase activity at autopsy compared with 10.9, 11.3, and 9.5 units/g fresh weight in two autopsy and one biopsy controls, respectively. The patient's renal cortical pyruvate carboxylase activity at autopsy was 0.008 +/- 0.004 units/g fresh weight compared with 5.05 units/g in the autopsy control. The patient had no detectable (less than 0.018 units/g fresh weight) cerebral pyruvate carboxylase activity at autopsy compared with 0.44, 0.53, and 0.695 units/g in the autopsy cerebrum of one human and two rhesus monkeys, respectively. Pyruvate dehydrogenase complex, phosphoenolpyruvate carboxykinase (PEPCK, EC 4.1.1.32), and fructose-1,6-bisphosphatase (EC 3.1.3.11) activities were in the normal range. The patient's urine pH was above 7.9 when the total serum CO2 was greater than 7.8 mM. However, the patient was able to acidify the urine to pH 5.1 when the total serum CO2 was 1.6 mM. The neuropathologic examination of the brain at autopsy revealed no sign of Leigh's disease, although developmental and degenerative lesions were observed. This is the first reported patient with a primary deficiency in hepatic, renal, and cerebral pyruvate carboxylase deficiency in whom the neuropathologic lesions, distinct from those of Leigh's disease, and proximal renal tubular acidosis have both been documented."}
{"id": "PMID:219408", "title": "Aversive conditioning in the sociopath.", "content": "Results of two experiments on differential conditioning of the skin conductance (SCR) in sociopaths and normal control subjects are described. In the first experiment it was found that an equal number of sociopaths and control subjects were aware of the conditioning contingency. However, only the normal subjects displayed reliable differential SCR conditioning. Sociopaths showed a dissociation between verbal learning and conditioning of a physiological change. The second experiment examined the differential conditioning of normal subjects and sociopaths in partial remission. The number of aware subjects in the two groups did not differ. Aware subjects in both groups showed differential SCR conditioning. Differential conditioning in sociopaths did not persist over trials as it did in control subjects. A deficiency in ACTH 4--10 as well as neurological dysfunctions were considered possible factors in the etiology of sociopathy. Further research on the relation of neuropeptides to the etiology and treatment of sociopathy is suggested.", "contents": "Aversive conditioning in the sociopath. Results of two experiments on differential conditioning of the skin conductance (SCR) in sociopaths and normal control subjects are described. In the first experiment it was found that an equal number of sociopaths and control subjects were aware of the conditioning contingency. However, only the normal subjects displayed reliable differential SCR conditioning. Sociopaths showed a dissociation between verbal learning and conditioning of a physiological change. The second experiment examined the differential conditioning of normal subjects and sociopaths in partial remission. The number of aware subjects in the two groups did not differ. Aware subjects in both groups showed differential SCR conditioning. Differential conditioning in sociopaths did not persist over trials as it did in control subjects. A deficiency in ACTH 4--10 as well as neurological dysfunctions were considered possible factors in the etiology of sociopathy. Further research on the relation of neuropeptides to the etiology and treatment of sociopathy is suggested."}
{"id": "PMID:219412", "title": "The QT interval in aborted sudden infant death syndrome infants.", "content": "The QT interval was measured in 12 normal and 7 aborted sudden infant death syndrome (SIDS) infants in rapid eye movement (REM) and quiet sleep at monthly intervals through the age of 4 months. An accuracy of better than 2 msec was assured by high resolution of the digitized signal and calibration of each QT measurement with an accurately generated time code. In contrast to current speculations, the QT index was significantly smaller in the infants with aborted SIDS than in the normal infants in both REM and quiet sleep (P less than 0.05). In addition, as in normal infants, the QTc was smaller in REM than in quiet sleep (P less than 0.01). Although these results offer no support for the hypothesis that SIDS results from prolongation of the QT interval, they suggest that aborted SIDS infants have a functional abnormality in the autonomic nervous system.", "contents": "The QT interval in aborted sudden infant death syndrome infants. The QT interval was measured in 12 normal and 7 aborted sudden infant death syndrome (SIDS) infants in rapid eye movement (REM) and quiet sleep at monthly intervals through the age of 4 months. An accuracy of better than 2 msec was assured by high resolution of the digitized signal and calibration of each QT measurement with an accurately generated time code. In contrast to current speculations, the QT index was significantly smaller in the infants with aborted SIDS than in the normal infants in both REM and quiet sleep (P less than 0.05). In addition, as in normal infants, the QTc was smaller in REM than in quiet sleep (P less than 0.01). Although these results offer no support for the hypothesis that SIDS results from prolongation of the QT interval, they suggest that aborted SIDS infants have a functional abnormality in the autonomic nervous system."}
{"id": "PMID:219413", "title": "Effect of sleep state on the QT interval in normal infants.", "content": "Twenty QT intervals selected at random from the middle periods of rapid eye movement (REM) and quiet sleep were measured in 12 normal infants studied at 2 weeks and 1, 2, 3, and 4 months of life. A digitizing system, consisting of a precision rotational potentiometer mounted on a pair of calipers and an A/D converter, was used for measurements. An accuracy of +/- 2 msec was achieved by high resolution of the digitized signal and calibration of each QT measurement with an accurately generated time code. Sleep staging was done visually using an electroencephalogram (EEG), an electrooculogram (EOG), a submental electromyogram (EMG), and behavioral criteria. Our results show that the QT index (QTc = QT/square rootRR) was significantly greater during quiet sleep (mean = 0.439) than during REM sleep (mean = 0.433) (P less than 0.01) and that this difference existed at all ages studied.", "contents": "Effect of sleep state on the QT interval in normal infants. Twenty QT intervals selected at random from the middle periods of rapid eye movement (REM) and quiet sleep were measured in 12 normal infants studied at 2 weeks and 1, 2, 3, and 4 months of life. A digitizing system, consisting of a precision rotational potentiometer mounted on a pair of calipers and an A/D converter, was used for measurements. An accuracy of +/- 2 msec was achieved by high resolution of the digitized signal and calibration of each QT measurement with an accurately generated time code. Sleep staging was done visually using an electroencephalogram (EEG), an electrooculogram (EOG), a submental electromyogram (EMG), and behavioral criteria. Our results show that the QT index (QTc = QT/square rootRR) was significantly greater during quiet sleep (mean = 0.439) than during REM sleep (mean = 0.433) (P less than 0.01) and that this difference existed at all ages studied."}
{"id": "PMID:219416", "title": "Development of ammonia and glucose productions from glutamine in foetal rat kidney; effects of metabolic acidosis.", "content": "Ammoniagenesis and gluconeogenesis have been studied in foetal rat kidneys during the five last days of gestation by measuring in vitro NH3 and glucose productions from glutamine and by assaying activities of soluble phosphoenolpyruvate carboxykinase(PEPCK) and glucose 6-phosphatase (G6Pase). These studies were carried out in normal (mean blood pH: 7.30) and acidotic (pH: 7.12) foetuses. In normal foetuses, NH3 production by kidney cortex slices remains constant throughout the studied period of development, at a level 10-fold lower than the maternal one. On day 20 of gestation, a low glucose production (20-fold lower than the maternal one) appears for the first time. This may be related to an increase of PEPCK and G6Pase activities which occurs between day 19 and 20. In 20 days old foetuses, NH4Cl induced acidosis stimulates NH3 production but has no effect on PEPCK activity and glucose production. A response of gluconeogenesis to acidosis is observed one day later (day 21).", "contents": "Development of ammonia and glucose productions from glutamine in foetal rat kidney; effects of metabolic acidosis. Ammoniagenesis and gluconeogenesis have been studied in foetal rat kidneys during the five last days of gestation by measuring in vitro NH3 and glucose productions from glutamine and by assaying activities of soluble phosphoenolpyruvate carboxykinase(PEPCK) and glucose 6-phosphatase (G6Pase). These studies were carried out in normal (mean blood pH: 7.30) and acidotic (pH: 7.12) foetuses. In normal foetuses, NH3 production by kidney cortex slices remains constant throughout the studied period of development, at a level 10-fold lower than the maternal one. On day 20 of gestation, a low glucose production (20-fold lower than the maternal one) appears for the first time. This may be related to an increase of PEPCK and G6Pase activities which occurs between day 19 and 20. In 20 days old foetuses, NH4Cl induced acidosis stimulates NH3 production but has no effect on PEPCK activity and glucose production. A response of gluconeogenesis to acidosis is observed one day later (day 21)."}
{"id": "PMID:219417", "title": "Anion dependence of the contractions of skinned cardiac cells.", "content": "Cardiac muscle fragments with disrupted sarcolemmas were prepared by homogenization of mouse ventricles. The rate of spontaneous contractions was increased when a solution containing isobutyrate as the main anion was substituted with a solution rich in chloride. At low calcium concentrations preparations which were quiescent in the isobutyrate solution responded to the chloride with a strong single contraction.", "contents": "Anion dependence of the contractions of skinned cardiac cells. Cardiac muscle fragments with disrupted sarcolemmas were prepared by homogenization of mouse ventricles. The rate of spontaneous contractions was increased when a solution containing isobutyrate as the main anion was substituted with a solution rich in chloride. At low calcium concentrations preparations which were quiescent in the isobutyrate solution responded to the chloride with a strong single contraction."}
{"id": "PMID:219418", "title": "Phosphorylation of molluscan paramyosin.", "content": "1. In Mytilus edulis two proteins of the contractile apparatus can be phosphorylated by cyclic AMP dependent protein kinases: a 295,000 d protein of unknown function, and paramyosin. 2. Paramyosin isolated from thick filaments by the selective extraction method contains the 106,000 d monomer only, whereas paramyosin extracted from ethanol ether dried powder contains equal amounts of the 108,000 d, and the 106,000 d monomers, and traces of the 104,000 d monomer. 3. Paramyosin isolated from ethanol ether dried powder incorporates up to four times the amount of 32P than paramyosin isolated by the selective extraction method. 4. Cytoplasmatic protein kinases show a higher affinity towards paramyosin as a phosphoryl acceptor than protein kinases associated with paramyosin. 5. Paramyosin of 5-HT treated catch muscles is phosphorylated 2 to 4 times better than paramyosin of ACh treated or untreated catch muscles.", "contents": "Phosphorylation of molluscan paramyosin. 1. In Mytilus edulis two proteins of the contractile apparatus can be phosphorylated by cyclic AMP dependent protein kinases: a 295,000 d protein of unknown function, and paramyosin. 2. Paramyosin isolated from thick filaments by the selective extraction method contains the 106,000 d monomer only, whereas paramyosin extracted from ethanol ether dried powder contains equal amounts of the 108,000 d, and the 106,000 d monomers, and traces of the 104,000 d monomer. 3. Paramyosin isolated from ethanol ether dried powder incorporates up to four times the amount of 32P than paramyosin isolated by the selective extraction method. 4. Cytoplasmatic protein kinases show a higher affinity towards paramyosin as a phosphoryl acceptor than protein kinases associated with paramyosin. 5. Paramyosin of 5-HT treated catch muscles is phosphorylated 2 to 4 times better than paramyosin of ACh treated or untreated catch muscles."}
{"id": "PMID:219419", "title": "Comparative chemical, biological and clinical studies of 99mtc-glucoheptonate and 99mtc-dimercaptosuccinate as used in renal scintigraphy.", "content": "The renal radiopharmaceutical preparations 99mTc-DMS and 99mTc-GH were examined chemically, biologically and clinically. Both preparations are of high radiochemical purity. The biodistribution of both preparations was examined in experimental animals at different time intervals, from 15 min to 4 hr; the precentage of incorporation of 99mTc-DMS into kindeys is much higher (29.4% to 52.0%) than that of 99mTc-GH (12.80% to 22.20%). Both preparations accumulate to a greater extent in the renal cortex than in the medulla. The most suitable time for renal scintigraphy for 99mTc-DMS is 90--150 min while for 99mTc-GH it is 60--90 min. It is concluded that 99mTc-DMS is more suitable for static scintigrams on the scanner and 99mTc-GH for dynamic studies with the gamma camera.", "contents": "Comparative chemical, biological and clinical studies of 99mtc-glucoheptonate and 99mtc-dimercaptosuccinate as used in renal scintigraphy. The renal radiopharmaceutical preparations 99mTc-DMS and 99mTc-GH were examined chemically, biologically and clinically. Both preparations are of high radiochemical purity. The biodistribution of both preparations was examined in experimental animals at different time intervals, from 15 min to 4 hr; the precentage of incorporation of 99mTc-DMS into kindeys is much higher (29.4% to 52.0%) than that of 99mTc-GH (12.80% to 22.20%). Both preparations accumulate to a greater extent in the renal cortex than in the medulla. The most suitable time for renal scintigraphy for 99mTc-DMS is 90--150 min while for 99mTc-GH it is 60--90 min. It is concluded that 99mTc-DMS is more suitable for static scintigrams on the scanner and 99mTc-GH for dynamic studies with the gamma camera."}
{"id": "PMID:219422", "title": "Mononeuropathy in diabetes mellitus: a phenomenon easily overlooked.", "content": "In patients with diabetes, a carefully taken history and meticulously performed neurologic examination enable the clinician to separate superimposed mononeuropathy from more generalized symmetric polyneuropathy. Recognition of mononeuroparhy is important, since often it is reversible.", "contents": "Mononeuropathy in diabetes mellitus: a phenomenon easily overlooked. In patients with diabetes, a carefully taken history and meticulously performed neurologic examination enable the clinician to separate superimposed mononeuropathy from more generalized symmetric polyneuropathy. Recognition of mononeuroparhy is important, since often it is reversible."}
{"id": "PMID:219425", "title": "A method of the rapid preparation of adenosine 5'-gamma-[32P] triphosphate by chemical synthesis.", "content": "A new chemical method for the synthesis of adenosine 5'-gamma-[32P] triphosphate has been developed based on the reaction of adenosine 5'-diphosphate with ethyl chloroformate. The resulting active mixed anhydride was able to react with [32P]-triethylammonium orthophosphate to give gamma-[32P]ATP.", "contents": "A method of the rapid preparation of adenosine 5'-gamma-[32P] triphosphate by chemical synthesis. A new chemical method for the synthesis of adenosine 5'-gamma-[32P] triphosphate has been developed based on the reaction of adenosine 5'-diphosphate with ethyl chloroformate. The resulting active mixed anhydride was able to react with [32P]-triethylammonium orthophosphate to give gamma-[32P]ATP."}
{"id": "PMID:219426", "title": "Purification of acetate kinase by affinity chromatography.", "content": "A one-step procedure using affinity chromatography has been shown to purify to apparent homogeneity acetate kinase from a commercially available preparation and to partially purify the enzyme from a crude, cell-free extract. Since the gel's capacity for enzyme adsorption is controlled by the thermodynamics of ligand-enzyme interaction, maximization of the adsorption isotherm was attempted. Enzyme adsorption decreased logarithmically with increasing ionic strength but increased with increasing concentration of MgCl2. These competing effects caused the net adsorption of enzyme to increase to a maximum and then to decrease as the MgCl2 concentration was raised. The results allow a significant improvement in affinity column performance and have important implications for scale-up procedures.", "contents": "Purification of acetate kinase by affinity chromatography. A one-step procedure using affinity chromatography has been shown to purify to apparent homogeneity acetate kinase from a commercially available preparation and to partially purify the enzyme from a crude, cell-free extract. Since the gel's capacity for enzyme adsorption is controlled by the thermodynamics of ligand-enzyme interaction, maximization of the adsorption isotherm was attempted. Enzyme adsorption decreased logarithmically with increasing ionic strength but increased with increasing concentration of MgCl2. These competing effects caused the net adsorption of enzyme to increase to a maximum and then to decrease as the MgCl2 concentration was raised. The results allow a significant improvement in affinity column performance and have important implications for scale-up procedures."}
{"id": "PMID:219427", "title": "[Glucose catabolite repression of glucoamylase biosynthesis by the yeast Endomycopsis fibuligera].", "content": "The effect of glucose, sucrose, fructose, maltose, alpha-methyl glucoside, glycerol, nonmetabolizing glucose analog--2-deoxy-D-glucose, and cyclic 3',5'-adenosine monophosphate (cAMP) on the glucoamylase biosynthesis by the yeast Endomycopsis fibuligera 20-9 was investigated. The sugars tested induced repression of the enzyme synthesis. The repressive effect of glucose, sucrose and maltose was reversed partially or completely by cAMP. The strongest derepressive effect of cAMP was noted in the presence of 2-deoxy-D-glucose. The transport of glucose and 2-deoxy-D-glucose in yeast cells was also investigated. Those compounds were found to compete for the entry into the cell. It is concluded that glucoamylase synthesis in Endomycopsis fibuligera 20-9 was susceptible to catabolite repression. Its possible mechanism discussed.", "contents": "[Glucose catabolite repression of glucoamylase biosynthesis by the yeast Endomycopsis fibuligera]. The effect of glucose, sucrose, fructose, maltose, alpha-methyl glucoside, glycerol, nonmetabolizing glucose analog--2-deoxy-D-glucose, and cyclic 3',5'-adenosine monophosphate (cAMP) on the glucoamylase biosynthesis by the yeast Endomycopsis fibuligera 20-9 was investigated. The sugars tested induced repression of the enzyme synthesis. The repressive effect of glucose, sucrose and maltose was reversed partially or completely by cAMP. The strongest derepressive effect of cAMP was noted in the presence of 2-deoxy-D-glucose. The transport of glucose and 2-deoxy-D-glucose in yeast cells was also investigated. Those compounds were found to compete for the entry into the cell. It is concluded that glucoamylase synthesis in Endomycopsis fibuligera 20-9 was susceptible to catabolite repression. Its possible mechanism discussed."}
{"id": "PMID:219437", "title": "Studies of whole-body retention and clearance of inhaled noble gases.", "content": "The in vivo measurements of 127Xe and 79Kr clearance from the whole body indicate five components, with biologic half-times ranging from 13 sec to 17.04 h. The slowest component correlated highly with percent total-body fat, the half-time varying between 7.59 and 17.04 for xenon and between 4.20 and 9.62 h for krypton. The long-term retention was localized to regions of high fat content as determined by the coincidence mode of the whole-body counter and images obtained with the scintillation camera. The estimated dose based on the retention data of this study would indicate increased doses to body fat and gonads as compared with those previously calculated. These increased doses are due to the longer retention of noble gases in fat. After 10-min inhalations of a mixture of 127Xe and air and 79Kr and air, approximately one third of the total 127Xe and one fifth of the total 79Kr were transferred to the body tissues, extrapolated back to the start of gas washout. Of this amount, approximately 13% of the 127Xe and approximately 9% of the 79Kr were associated with the slowest component.", "contents": "Studies of whole-body retention and clearance of inhaled noble gases. The in vivo measurements of 127Xe and 79Kr clearance from the whole body indicate five components, with biologic half-times ranging from 13 sec to 17.04 h. The slowest component correlated highly with percent total-body fat, the half-time varying between 7.59 and 17.04 for xenon and between 4.20 and 9.62 h for krypton. The long-term retention was localized to regions of high fat content as determined by the coincidence mode of the whole-body counter and images obtained with the scintillation camera. The estimated dose based on the retention data of this study would indicate increased doses to body fat and gonads as compared with those previously calculated. These increased doses are due to the longer retention of noble gases in fat. After 10-min inhalations of a mixture of 127Xe and air and 79Kr and air, approximately one third of the total 127Xe and one fifth of the total 79Kr were transferred to the body tissues, extrapolated back to the start of gas washout. Of this amount, approximately 13% of the 127Xe and approximately 9% of the 79Kr were associated with the slowest component."}
{"id": "PMID:219443", "title": "Studies of the mechanisms involved in the fate of prostacyclin (PGI2) and 6-keto-PGF1alpha in the pulmonary circulation.", "content": "We have investigated the metabolism of [3]H-prostaglandin (PG)I2 and its non-enzymatic breakdown product [3]H-6-keto-PGF1alpha by rat pulmonary tissue and their possible uptake and metabolism upon passage through the isolated perfused rat lung. When incubated with rat lung homogenate in the presence of beta-NAD, [3]H-PGI2 was extensively degraded into at least one metabolite, while [3]H-6-keto-PGF1alpha was only minimally metabolized. However, on passage through isolated perfused rat lungs, neither [3]H-PGI2 nor [3]H-6-keto-PGF1alpha were removed from the circulation into the lung or degraded. This demonstration that PGI2 is not a substrate for the transport system for the removal of PGs from the circulation into the lung further illustrates that this system is a critical determinant for the pulmonary inactivation of circulating prostaglandins. The experimental findings are discussed in reference ot the structure-activity requirements necessary for pulmonary transport and subsequent metabolism.", "contents": "Studies of the mechanisms involved in the fate of prostacyclin (PGI2) and 6-keto-PGF1alpha in the pulmonary circulation. We have investigated the metabolism of [3]H-prostaglandin (PG)I2 and its non-enzymatic breakdown product [3]H-6-keto-PGF1alpha by rat pulmonary tissue and their possible uptake and metabolism upon passage through the isolated perfused rat lung. When incubated with rat lung homogenate in the presence of beta-NAD, [3]H-PGI2 was extensively degraded into at least one metabolite, while [3]H-6-keto-PGF1alpha was only minimally metabolized. However, on passage through isolated perfused rat lungs, neither [3]H-PGI2 nor [3]H-6-keto-PGF1alpha were removed from the circulation into the lung or degraded. This demonstration that PGI2 is not a substrate for the transport system for the removal of PGs from the circulation into the lung further illustrates that this system is a critical determinant for the pulmonary inactivation of circulating prostaglandins. The experimental findings are discussed in reference ot the structure-activity requirements necessary for pulmonary transport and subsequent metabolism."}
{"id": "PMID:219444", "title": "Effect of prostacyclin on myogenic activity and adrenergic neuroeffector interaction in canine isolated veins.", "content": "In isolated strips of canine mesenteric vein prostacyclin (PGI2) causes a dose-dependent depression of the amplitude of the spontaneous rhythmic contractions without influencing their frequency. This suggests that prostacyclin affects the events leading from the depolarization of the smooth muscle cells to their contractions, rather than the induction of the myogenic activity itself. Furthermore, prostacyclin reduces the noradrenaline-induced contraction of the canine saphenous vein without affecting the electrically induced responses, suggesting a possible dual effect of the drug: at the smooth muscle it causes depression of the responsiveness to noradrenaline whereas at the adrenergic nerve endings it enhances the evoked release of the adrenergic transmitter.", "contents": "Effect of prostacyclin on myogenic activity and adrenergic neuroeffector interaction in canine isolated veins. In isolated strips of canine mesenteric vein prostacyclin (PGI2) causes a dose-dependent depression of the amplitude of the spontaneous rhythmic contractions without influencing their frequency. This suggests that prostacyclin affects the events leading from the depolarization of the smooth muscle cells to their contractions, rather than the induction of the myogenic activity itself. Furthermore, prostacyclin reduces the noradrenaline-induced contraction of the canine saphenous vein without affecting the electrically induced responses, suggesting a possible dual effect of the drug: at the smooth muscle it causes depression of the responsiveness to noradrenaline whereas at the adrenergic nerve endings it enhances the evoked release of the adrenergic transmitter."}
{"id": "PMID:219445", "title": "The role of various prostaglandins on the correlation between permeability to albumin and cAMP levels in the isolated mesentery.", "content": "Prostaglandins (PG) have been shown to raise the level of cyclic AMP (cAMP) in various tissues, and to increase permeability. Whether both events are linked, is at present a matter of speculation. We have investigated the effects of PGE1, E2, A1, A2, F1alpha and F2alpha on an isolated rat mesentery placed in a diffusion cell (surface area : 2 sq.cm). The PGs (5 microgram/ml) increased the passage of (I 125) - Albumin across the mesentery. In other experiments, diks of rat mesentery (surface area : 2 sq.cm) have been incubated in assay tubes, and cAMP levels measured by a binding protein assay. We have observed an excellent correlation between increases in permeability and cAMP levels (r=0.961). In order of increasing potency on both parameters, the PGs may be classified as follows : PGF, PGA and PGE. In the rat mesentery, under the influence of prostaglandins, increases in permeability and in cAMP levels are apparently connected.", "contents": "The role of various prostaglandins on the correlation between permeability to albumin and cAMP levels in the isolated mesentery. Prostaglandins (PG) have been shown to raise the level of cyclic AMP (cAMP) in various tissues, and to increase permeability. Whether both events are linked, is at present a matter of speculation. We have investigated the effects of PGE1, E2, A1, A2, F1alpha and F2alpha on an isolated rat mesentery placed in a diffusion cell (surface area : 2 sq.cm). The PGs (5 microgram/ml) increased the passage of (I 125) - Albumin across the mesentery. In other experiments, diks of rat mesentery (surface area : 2 sq.cm) have been incubated in assay tubes, and cAMP levels measured by a binding protein assay. We have observed an excellent correlation between increases in permeability and cAMP levels (r=0.961). In order of increasing potency on both parameters, the PGs may be classified as follows : PGF, PGA and PGE. In the rat mesentery, under the influence of prostaglandins, increases in permeability and in cAMP levels are apparently connected."}
{"id": "PMID:219448", "title": "[Hepato-cellular carcinoma associated with HBs antigen: a study of 25 cases from Vietnam (author's transl)].", "content": "Using orcein staining and indirect immunofluorescence on paraffin sections, the authors demonstrated HBs Ag in 64% of 25 hepatocellular carcinomas (including \"bone metastasis\") in Vietnam. The main findings in the literature suggesting a causal role for hepatitis B virus in primary liver cancer are discussed.", "contents": "[Hepato-cellular carcinoma associated with HBs antigen: a study of 25 cases from Vietnam (author's transl)]. Using orcein staining and indirect immunofluorescence on paraffin sections, the authors demonstrated HBs Ag in 64% of 25 hepatocellular carcinomas (including \"bone metastasis\") in Vietnam. The main findings in the literature suggesting a causal role for hepatitis B virus in primary liver cancer are discussed."}
{"id": "PMID:219454", "title": "Effects of cyclic AMP altering drugs on endotoxin-induced termination of pregnancy.", "content": "The effects of dibutyryl-cyclic AMP (DBcAMP), propranolol, and theophylline on endotoxin (LPS) challenged pregnant mice was determined by comparing the patterns of termination and times of fetal expulsion. Endotoxin isolated from wild type (WT) and Re chemotype mutant cells of Salmonella typhimurium was used. Wild type LPS caused the expulsion of the fetuses, while Re LPS primarily caused the resorption of the fetuses. The major change in pattern occurred in the propranolol treated Re LPS challenged group with a trend toward more expulsions and a decrease in uterine cyclic AMP (cAMP) levels to that approaching the group challenged with wild type LPS. The time of expulsion was also affected in the wild type LPS treated group, with propranolol hastening and DBcAMP and theophylline delaying the expulsion. These results support the hypothesis that uterine cAMP is involved in the expulsion of the fetuses.", "contents": "Effects of cyclic AMP altering drugs on endotoxin-induced termination of pregnancy. The effects of dibutyryl-cyclic AMP (DBcAMP), propranolol, and theophylline on endotoxin (LPS) challenged pregnant mice was determined by comparing the patterns of termination and times of fetal expulsion. Endotoxin isolated from wild type (WT) and Re chemotype mutant cells of Salmonella typhimurium was used. Wild type LPS caused the expulsion of the fetuses, while Re LPS primarily caused the resorption of the fetuses. The major change in pattern occurred in the propranolol treated Re LPS challenged group with a trend toward more expulsions and a decrease in uterine cyclic AMP (cAMP) levels to that approaching the group challenged with wild type LPS. The time of expulsion was also affected in the wild type LPS treated group, with propranolol hastening and DBcAMP and theophylline delaying the expulsion. These results support the hypothesis that uterine cAMP is involved in the expulsion of the fetuses."}
{"id": "PMID:219455", "title": "Ethanol inhibits testosterone biosynthesis by direct action on Leydig cells.", "content": "Ethanol was found to suppress gonadotropin-stimulated testosterone biosynthesis in sexually mature male rats in vivo and in intact Leydig cells in vitro. A similar ethanol dose-response inhibition curve was also observed when either whole or homogenized cells were stimulated by dibutyryl cyclic AMP. In the presence of pharmacologically relevant ethanol concentrations, added NAD+ restored testosterone production to stimulated control levels. These results demonstrate a direct inhibitory effect of ethanol on testicular testosterone synthesis. The site of inhibition is primarily intracellular and the mechanism is probably through a decrease in the NAD+/NADH ratio caused by ethanol oxidation.", "contents": "Ethanol inhibits testosterone biosynthesis by direct action on Leydig cells. Ethanol was found to suppress gonadotropin-stimulated testosterone biosynthesis in sexually mature male rats in vivo and in intact Leydig cells in vitro. A similar ethanol dose-response inhibition curve was also observed when either whole or homogenized cells were stimulated by dibutyryl cyclic AMP. In the presence of pharmacologically relevant ethanol concentrations, added NAD+ restored testosterone production to stimulated control levels. These results demonstrate a direct inhibitory effect of ethanol on testicular testosterone synthesis. The site of inhibition is primarily intracellular and the mechanism is probably through a decrease in the NAD+/NADH ratio caused by ethanol oxidation."}
{"id": "PMID:219460", "title": "[Bilateral isolated trigeminal neuropathy (author's transl)].", "content": "Spillane and Wells (1959) were the first to describe the syndrome known as isolated trigeminal neuropathy in which deficit in the trigeminal nerve occurs either unilaterally or bilaterally without evidence of any local lesion. It may be a truly isolated disorder but can also be the predominant element of a more diffuse neuropathy provoking, more particularly, ageusia and anosmia. The bilateral forms are fairly frequently related to connective tissue diseases but many are of unknown aetiology. A case is reported of the bilateral form with ageusia and anosmia, cubital deficit, and slowing of the conduction rate in the limbs. No aetiology was found.", "contents": "[Bilateral isolated trigeminal neuropathy (author's transl)]. Spillane and Wells (1959) were the first to describe the syndrome known as isolated trigeminal neuropathy in which deficit in the trigeminal nerve occurs either unilaterally or bilaterally without evidence of any local lesion. It may be a truly isolated disorder but can also be the predominant element of a more diffuse neuropathy provoking, more particularly, ageusia and anosmia. The bilateral forms are fairly frequently related to connective tissue diseases but many are of unknown aetiology. A case is reported of the bilateral form with ageusia and anosmia, cubital deficit, and slowing of the conduction rate in the limbs. No aetiology was found."}
{"id": "PMID:219461", "title": "[Isolated sensory trigeminal neuropathy (author's transl)].", "content": "Three cases of the disease are reported by the author. Clinical observations showed them to be unilateral lesions, not affecting the Vth motor nerve fibers, and without any other neurological disorder. The lesions had been present for 16, 8, and 2 years respectively. Radiography and tomography of the petrous bone was normal, as was tomodensitometry in the third case. The three patient developed a syndrome with dysesthesia and hypoesthesia after several weeks or months, and this remained fairly constant. In such cases which progress over a long period of time, in which there is no anatomical basis, and in which no aetiology can be found, the only conclusions to be drawn are clinical ones: that this is a true syndrome of chronic isolated sensory neuropathy of the trigeminal nerve.", "contents": "[Isolated sensory trigeminal neuropathy (author's transl)]. Three cases of the disease are reported by the author. Clinical observations showed them to be unilateral lesions, not affecting the Vth motor nerve fibers, and without any other neurological disorder. The lesions had been present for 16, 8, and 2 years respectively. Radiography and tomography of the petrous bone was normal, as was tomodensitometry in the third case. The three patient developed a syndrome with dysesthesia and hypoesthesia after several weeks or months, and this remained fairly constant. In such cases which progress over a long period of time, in which there is no anatomical basis, and in which no aetiology can be found, the only conclusions to be drawn are clinical ones: that this is a true syndrome of chronic isolated sensory neuropathy of the trigeminal nerve."}
{"id": "PMID:219462", "title": "[Clinical and laboratory aspects of 2 cases of cutaneous leishmaniasis].", "content": "Two cases of cutaneous leishmaniasis in a mother and her son, contracted during a trip in Libya, are reported. The diagnosis was established on the basis of the clinical aspect and epidemiological data, and confirmed by laboratory tests. A specific treatment with Fuadin was applied.", "contents": "[Clinical and laboratory aspects of 2 cases of cutaneous leishmaniasis]. Two cases of cutaneous leishmaniasis in a mother and her son, contracted during a trip in Libya, are reported. The diagnosis was established on the basis of the clinical aspect and epidemiological data, and confirmed by laboratory tests. A specific treatment with Fuadin was applied."}
{"id": "PMID:219466", "title": "Relationship between life stress factors and viral antibody levels in patients with juvenile rheumatoid arthritis.", "content": "Serum specimens from 46 patients with JRA were tested for measles CF, HI, HLI, and RNP-GP antibodies, for rubella HI antibodies, and for adenovirus and herpes simplex virus CF antibodies. The mean antibody titres of the 16 JRA patients of the major conflict group (14) were generally higher than those of the 30 patients of the non-conflict group, although the differences do not reach the level of statistical significance. The interrelationships between life stress, emotions and immunological changes in JRA are discussed.", "contents": "Relationship between life stress factors and viral antibody levels in patients with juvenile rheumatoid arthritis. Serum specimens from 46 patients with JRA were tested for measles CF, HI, HLI, and RNP-GP antibodies, for rubella HI antibodies, and for adenovirus and herpes simplex virus CF antibodies. The mean antibody titres of the 16 JRA patients of the major conflict group (14) were generally higher than those of the 30 patients of the non-conflict group, although the differences do not reach the level of statistical significance. The interrelationships between life stress, emotions and immunological changes in JRA are discussed."}
{"id": "PMID:219468", "title": "[Curability of malignant neoplasms: value and limitations of chemotherapy].", "content": "Cancer chemotherapy was purely palliative until the early sixties. Tumor cures have been since obtained, first in malignant trophoblastoma and Burkitt's lymphoma, and more recently in Hodgkin's disease, diffuse histiocytic lymphoma, acute lymphocytic leukemia in children, Wilms's tumor and osteosarcoma. Preliminary data are suggestive of tumor cures in testicular teratomas and, possibly, in small cell carcinoma of the lung. Five patients with trophoblastoma, Hodgkin's disease, melanoma, chronic myelocytic leukemia and anaplastic carcinoma of the lung are briefly presented, all without evidence of tumor relapse 3 years or more after chemotherapy. Theoretical bases for improvement of the curative effect of cancer chemotherapy are discussed, including the development of new agents, and new pharmacological problems concerning drug interactions, complexes of drugs with macromolecules or immunoglobulins and liposomes are considered.", "contents": "[Curability of malignant neoplasms: value and limitations of chemotherapy]. Cancer chemotherapy was purely palliative until the early sixties. Tumor cures have been since obtained, first in malignant trophoblastoma and Burkitt's lymphoma, and more recently in Hodgkin's disease, diffuse histiocytic lymphoma, acute lymphocytic leukemia in children, Wilms's tumor and osteosarcoma. Preliminary data are suggestive of tumor cures in testicular teratomas and, possibly, in small cell carcinoma of the lung. Five patients with trophoblastoma, Hodgkin's disease, melanoma, chronic myelocytic leukemia and anaplastic carcinoma of the lung are briefly presented, all without evidence of tumor relapse 3 years or more after chemotherapy. Theoretical bases for improvement of the curative effect of cancer chemotherapy are discussed, including the development of new agents, and new pharmacological problems concerning drug interactions, complexes of drugs with macromolecules or immunoglobulins and liposomes are considered."}
{"id": "PMID:219469", "title": "[Chronic treatment of hypertension by an inhibitor of angiotensin converting enzyme].", "content": "Captopril, or SQ 14,225 an orally active inhibitor of angiotensin-converting enzyme, produced a significant blood pressure reduction in 26 hypertensives. This new drug, alone or combined with a diuretic, has normalized the blood pressure of the 22 patients on long-term treatment.", "contents": "[Chronic treatment of hypertension by an inhibitor of angiotensin converting enzyme]. Captopril, or SQ 14,225 an orally active inhibitor of angiotensin-converting enzyme, produced a significant blood pressure reduction in 26 hypertensives. This new drug, alone or combined with a diuretic, has normalized the blood pressure of the 22 patients on long-term treatment."}
{"id": "PMID:219470", "title": "[Effect of the lipid-lowering agent, procetofen, on the makeup of human biliary lipids].", "content": "The effect of lipid-lowering treatment with procetofen (3 x 100 mg/day for 4-6 weeks) on the cholesterol saturation index (S.I.) of bile has been studied in 6 patients with type IIa or IIb pattern hyperlipoproteinemia. Compared with a control period with placebo, the S.I. was increased by more than 20% during active treatment in 2 patients. Oversaturation was reached in one case. In the other 4 patients, the changes did not exceed 20% of the control value. Thus, increased lithogenicity of bile does not appear to be a frequent effect of procetofen. A larger number of patients should therefore be studied to establish its true incidence.", "contents": "[Effect of the lipid-lowering agent, procetofen, on the makeup of human biliary lipids]. The effect of lipid-lowering treatment with procetofen (3 x 100 mg/day for 4-6 weeks) on the cholesterol saturation index (S.I.) of bile has been studied in 6 patients with type IIa or IIb pattern hyperlipoproteinemia. Compared with a control period with placebo, the S.I. was increased by more than 20% during active treatment in 2 patients. Oversaturation was reached in one case. In the other 4 patients, the changes did not exceed 20% of the control value. Thus, increased lithogenicity of bile does not appear to be a frequent effect of procetofen. A larger number of patients should therefore be studied to establish its true incidence."}
{"id": "PMID:219471", "title": "[The effect of diuretic therapy on serum lipoproteins: an undesirable effect?].", "content": "The effect of diuretics on serum lipids and lipoproteins was evaluated in 23 patients with essential hypertension treated with chlorthalidone for six weeks. Compared to placebo conditions, diuretic therapy significantly increased serum beta (+8%, p less than 0.05) or low-density-lipoprotein (LP) cholesterol (+17%, p less than 0.025). Since alpha-LP or high-density-LP cholesterol was unchanged or tended to decrease slightly, there was also an increase in the beta/alpha-LP (+26%, p less than 0.025) or low/high-density-LP cholesterol (21%, p less than 0.025) ratio. Serum cholesterol (+4%), triglycerides (+3%), phospholipids and the Apo-LP A-I, A-II and B were not changed significantly. Blood pressure and plasma potassium were decreased (p less than 0.01), blood volume and serum insulin were not changed significantly, and serum glucose was increased mildly. Plasma renin, aldosterone and norepinephrine levels rose significantly (p less than 0.05), while circulating epinephrine was unaltered. Alterations in LP were not related to variations in blood pressure, blood volume, plasma electrolytes or serum glucose or insulin; and they did not correlate with chlorthalidone-induced increases in plasma renin, aldosterone or norepinephrine. Treatment with certain diuretics may have an adverse influence on lipoprotein metabolism.", "contents": "[The effect of diuretic therapy on serum lipoproteins: an undesirable effect?]. The effect of diuretics on serum lipids and lipoproteins was evaluated in 23 patients with essential hypertension treated with chlorthalidone for six weeks. Compared to placebo conditions, diuretic therapy significantly increased serum beta (+8%, p less than 0.05) or low-density-lipoprotein (LP) cholesterol (+17%, p less than 0.025). Since alpha-LP or high-density-LP cholesterol was unchanged or tended to decrease slightly, there was also an increase in the beta/alpha-LP (+26%, p less than 0.025) or low/high-density-LP cholesterol (21%, p less than 0.025) ratio. Serum cholesterol (+4%), triglycerides (+3%), phospholipids and the Apo-LP A-I, A-II and B were not changed significantly. Blood pressure and plasma potassium were decreased (p less than 0.01), blood volume and serum insulin were not changed significantly, and serum glucose was increased mildly. Plasma renin, aldosterone and norepinephrine levels rose significantly (p less than 0.05), while circulating epinephrine was unaltered. Alterations in LP were not related to variations in blood pressure, blood volume, plasma electrolytes or serum glucose or insulin; and they did not correlate with chlorthalidone-induced increases in plasma renin, aldosterone or norepinephrine. Treatment with certain diuretics may have an adverse influence on lipoprotein metabolism."}
{"id": "PMID:219472", "title": "[Lead poisoning. Apropos of a case of acute encephalopathy in an adult].", "content": "Although acute lead encephalopathy is rare in adults, the authors had the opportunity to observe a case in a patient who had been exposed to lead occupationally for 25 years. This patient was also seen to be suffering from anemia and polyneuropathy. The blood lead level was 591 micrograms/100 ml (28,52 mumol/l). A review of the literature concerning the principal sources of lead poisoning, routes of absorption, metabolism and consequences of poisoning is conducted. Treatment by chelating agents is discussed. CaNa2-EDTA was administered by i.v. infusion over 24 hours and a favorable evolution was rapidly observable in the encephalopathy and anemia. On the other hand, the polyneuropathy was intensified, a fact which may have been caused by redistribution of lead in the soft tissues.", "contents": "[Lead poisoning. Apropos of a case of acute encephalopathy in an adult]. Although acute lead encephalopathy is rare in adults, the authors had the opportunity to observe a case in a patient who had been exposed to lead occupationally for 25 years. This patient was also seen to be suffering from anemia and polyneuropathy. The blood lead level was 591 micrograms/100 ml (28,52 mumol/l). A review of the literature concerning the principal sources of lead poisoning, routes of absorption, metabolism and consequences of poisoning is conducted. Treatment by chelating agents is discussed. CaNa2-EDTA was administered by i.v. infusion over 24 hours and a favorable evolution was rapidly observable in the encephalopathy and anemia. On the other hand, the polyneuropathy was intensified, a fact which may have been caused by redistribution of lead in the soft tissues."}
{"id": "PMID:219473", "title": "[Kala-azar; clinical and physiopathological study a propos of a new case studied in Switzerland].", "content": "Kala-azar, a parasitic disease caused by Leishmania donovani, is usually found in tropical areas but may occasionally occur in other regions such as the Mediterranean. A case of kala-azar in a women who had been on a holiday in Greece is reported. The parasite was demonstrated in lymph node biopsies and bone marrow smears and treatment with stibogluconate was begun. High levels of circulating immune complexes were demonstrable before and during the demonstration of parasites; the immune complexes were partially characterized. The diminution of complexes in serum paralleled the regression of clinical symptoms, suggesting a relationship between the clinical course and levels of circulating immune complexes. The disease may be a serum sickness-like syndrome induced by the parasite.", "contents": "[Kala-azar; clinical and physiopathological study a propos of a new case studied in Switzerland]. Kala-azar, a parasitic disease caused by Leishmania donovani, is usually found in tropical areas but may occasionally occur in other regions such as the Mediterranean. A case of kala-azar in a women who had been on a holiday in Greece is reported. The parasite was demonstrated in lymph node biopsies and bone marrow smears and treatment with stibogluconate was begun. High levels of circulating immune complexes were demonstrable before and during the demonstration of parasites; the immune complexes were partially characterized. The diminution of complexes in serum paralleled the regression of clinical symptoms, suggesting a relationship between the clinical course and levels of circulating immune complexes. The disease may be a serum sickness-like syndrome induced by the parasite."}
{"id": "PMID:219475", "title": "Genetic mapping of the ecotropic murine leukemia virus-inducing locus of BALB/c mouse to chromosome 5.", "content": "By means of an approach that combined the techniques of somatic cell genetics and Mendelian breeding studies, the inducibility locus, designated Cv, for ecotropic murine leukemia virus in BALB/c mice, was mapped to chromosome 5, 23 units from the locus for phosphoglucomutase-1, with gene order Cv-Pgm-1-Gus. This low-efficiency inducibility locus is therefore not allelic with the chromosome 7 loci previously described for two other mouse strains with high virus inducibility. These studies provide further evidence that endogenous ecotropic viruses represent viral genomes inserted at different chromosomal sites in the various mouse strains.", "contents": "Genetic mapping of the ecotropic murine leukemia virus-inducing locus of BALB/c mouse to chromosome 5. By means of an approach that combined the techniques of somatic cell genetics and Mendelian breeding studies, the inducibility locus, designated Cv, for ecotropic murine leukemia virus in BALB/c mice, was mapped to chromosome 5, 23 units from the locus for phosphoglucomutase-1, with gene order Cv-Pgm-1-Gus. This low-efficiency inducibility locus is therefore not allelic with the chromosome 7 loci previously described for two other mouse strains with high virus inducibility. These studies provide further evidence that endogenous ecotropic viruses represent viral genomes inserted at different chromosomal sites in the various mouse strains."}
{"id": "PMID:219476", "title": "Genetic linkage of C3H/HeJ and BALB/c endogenous ecotropic C-type viruses to phosphoglucomutase-1 on chromosome 5.", "content": "The genetic linkage of the endogenous C3H/HeJ C-type ecotropic virus to phosphoglucomutase-1 (0.28, recombinant fraction) on chromosome 5 was established by means of serological assays of backcrossed mice. With a combination of serological techniques and DNA-DNA hybridization the BALB/c endogenous ecotropic virus was shown to be either closely linked or allelic with the C3H/HeJ locus.", "contents": "Genetic linkage of C3H/HeJ and BALB/c endogenous ecotropic C-type viruses to phosphoglucomutase-1 on chromosome 5. The genetic linkage of the endogenous C3H/HeJ C-type ecotropic virus to phosphoglucomutase-1 (0.28, recombinant fraction) on chromosome 5 was established by means of serological assays of backcrossed mice. With a combination of serological techniques and DNA-DNA hybridization the BALB/c endogenous ecotropic virus was shown to be either closely linked or allelic with the C3H/HeJ locus."}
{"id": "PMID:219477", "title": "A source of nonshivering thermogenesis in fur seal skeletal muscle.", "content": "The mitochondria from the subscapular muscle of naturally cold-stressed 10- to 15-year-old northern fur seals (Callorhinus ursinus) were loosely coupled upon isolation, whereas the mitochondria from the same muscle of warm-acclimated pups of the same age were tightly coupled. Thus, loose-coupled muscle mitochondria might provide an important vehicle for nonshivering thermogenesis in this species.", "contents": "A source of nonshivering thermogenesis in fur seal skeletal muscle. The mitochondria from the subscapular muscle of naturally cold-stressed 10- to 15-year-old northern fur seals (Callorhinus ursinus) were loosely coupled upon isolation, whereas the mitochondria from the same muscle of warm-acclimated pups of the same age were tightly coupled. Thus, loose-coupled muscle mitochondria might provide an important vehicle for nonshivering thermogenesis in this species."}
{"id": "PMID:219478", "title": "Ingested mineral fibers: elimination in human urine.", "content": "Sediment in human urine examined by transmission electron microscopy contains amphibole fibers which originate from the ingestion of drinking water contaminated with these mineral fibers. The ingestion of filtered water results in the eventual disappearance of amphibole fibers from urine. These observations provide the first direct evidence for the passage of mineral fibers through the human gastro-intestinal mucosa under normal conditions of the alimentary canal.", "contents": "Ingested mineral fibers: elimination in human urine. Sediment in human urine examined by transmission electron microscopy contains amphibole fibers which originate from the ingestion of drinking water contaminated with these mineral fibers. The ingestion of filtered water results in the eventual disappearance of amphibole fibers from urine. These observations provide the first direct evidence for the passage of mineral fibers through the human gastro-intestinal mucosa under normal conditions of the alimentary canal."}
{"id": "PMID:219480", "title": "Evolutionary relatedness of viper and primate endogenous retroviruses.", "content": "A retrovirus previously isolated from a tumored Russell's viper is shown by molecular hybridization to be an endogenous virus of this reptilian species. Radio-immunologic techniques revealed that the viper retrovirus is immunologically and, hence, evolutionarily related to endogenous type D retorviruses of Old World primates. These findings extend the number of vertebrate classes possessing endogenous retroviruses and suggest that type D retroviruses may even be more widely distributed in nature than type C retroviruses.", "contents": "Evolutionary relatedness of viper and primate endogenous retroviruses. A retrovirus previously isolated from a tumored Russell's viper is shown by molecular hybridization to be an endogenous virus of this reptilian species. Radio-immunologic techniques revealed that the viper retrovirus is immunologically and, hence, evolutionarily related to endogenous type D retorviruses of Old World primates. These findings extend the number of vertebrate classes possessing endogenous retroviruses and suggest that type D retroviruses may even be more widely distributed in nature than type C retroviruses."}
{"id": "PMID:219481", "title": "Localization of the neurally mediated arrhythmogenic properties of digitalis.", "content": "Available evidence suggests that the propensity of digitalis glycosides to produce cardiac arrhythmias is due in part to their neuroexictatory effects. We have performed experiments in cats which support the existence of a neurogenic component in the etiology of digitalis-induced ventricular arrhythmias. Our data further indicate that the locus of this neural effect lies within an area of the medulla 2 millimeters above to 2 millimeters below the obex. These findings, when considered with the effects of polar cardiac glycosides that do not cross the blood-brain barrier, suggest that the area postrema may be the site of neural activation.", "contents": "Localization of the neurally mediated arrhythmogenic properties of digitalis. Available evidence suggests that the propensity of digitalis glycosides to produce cardiac arrhythmias is due in part to their neuroexictatory effects. We have performed experiments in cats which support the existence of a neurogenic component in the etiology of digitalis-induced ventricular arrhythmias. Our data further indicate that the locus of this neural effect lies within an area of the medulla 2 millimeters above to 2 millimeters below the obex. These findings, when considered with the effects of polar cardiac glycosides that do not cross the blood-brain barrier, suggest that the area postrema may be the site of neural activation."}
{"id": "PMID:219483", "title": "[Needle biopsy of the liver in an internal medicine department].", "content": "The authors presents 1 129 liver biopsies done during 7 years in a service of general medicine. Three accidents has been encountered representing a 0,17% mortality. Histologically, 50% of patients presented alterations due to ethylism, 25% presented a normal liver picture, which can be a diagnosis argument; 20% presented various lesions, of which tuberculosis is predominant, as well as acute, parasitary or hematological livers. Only 5% of the histological pictures are ininterpretable. The liver biopsy done very early in the evolution of a disease is sometimes a diagnosis argument which superior to others, allowing the rapid installation of the necessary treatment.", "contents": "[Needle biopsy of the liver in an internal medicine department]. The authors presents 1 129 liver biopsies done during 7 years in a service of general medicine. Three accidents has been encountered representing a 0,17% mortality. Histologically, 50% of patients presented alterations due to ethylism, 25% presented a normal liver picture, which can be a diagnosis argument; 20% presented various lesions, of which tuberculosis is predominant, as well as acute, parasitary or hematological livers. Only 5% of the histological pictures are ininterpretable. The liver biopsy done very early in the evolution of a disease is sometimes a diagnosis argument which superior to others, allowing the rapid installation of the necessary treatment."}
{"id": "PMID:219485", "title": "[Degenerative angiodysplasia of the ascending colon: a new entity frequently responsible for intestinal hemorrhage in the elderly].", "content": "The authors report a case of degenerative angiodysplasia of the right side of the colon. Regarding this they describe the two clinical features peculiar to this new nosological anatomo-clinical entity: hypochromic anaemia associated with low iron, and intestinal haemorrhage. The improvement of selective arteriography is the method which permits its description and underlines the frequence. But the authors believe that coloscopy in the presence of these lesions, should become beneficial and hold a place of special importance: in the diagnosis and concerning treatment of this disease. In effect the patients most prone to this condition are, by definition, elderly and hardly suitable subjects for surgery.", "contents": "[Degenerative angiodysplasia of the ascending colon: a new entity frequently responsible for intestinal hemorrhage in the elderly]. The authors report a case of degenerative angiodysplasia of the right side of the colon. Regarding this they describe the two clinical features peculiar to this new nosological anatomo-clinical entity: hypochromic anaemia associated with low iron, and intestinal haemorrhage. The improvement of selective arteriography is the method which permits its description and underlines the frequence. But the authors believe that coloscopy in the presence of these lesions, should become beneficial and hold a place of special importance: in the diagnosis and concerning treatment of this disease. In effect the patients most prone to this condition are, by definition, elderly and hardly suitable subjects for surgery."}
{"id": "PMID:219486", "title": "[Passive hemagglutination test for individual or epidemiologic diagnosis of human brucellosis].", "content": "Coupling of an extract from B. abortus strain 99 to sheep red blood cells by chromium chloride allowed to develop a highly specific and reliable passive hemagglutination test (H). Indeed, H was positive in 99.8 per cent sera from 968 known Brucella-infected heifers, while tube agglutination revealed only 59 per cent and complement fixation 90.9 per cent positive cases. H was positive in 153 sera from 778 proven or suspected human brucellosis where agglutination and/or complement fixation tests were positive, and in 21 sera negative to conventional tests. H demonstreated remote or undiagnosed human B. abortus infections in 28.6 per cent of 18 367 human sera randomly examined in a rural area. Therefore, a simple easy-to-perform passive hemagglutination test could replace a battery of conventional tests for the diagnosis of individual brucellosis, and epidemiologic surveys. The present study points to a high prevalence of undiagnosed brucellosis in man, specially in those area where cattle are raised.", "contents": "[Passive hemagglutination test for individual or epidemiologic diagnosis of human brucellosis]. Coupling of an extract from B. abortus strain 99 to sheep red blood cells by chromium chloride allowed to develop a highly specific and reliable passive hemagglutination test (H). Indeed, H was positive in 99.8 per cent sera from 968 known Brucella-infected heifers, while tube agglutination revealed only 59 per cent and complement fixation 90.9 per cent positive cases. H was positive in 153 sera from 778 proven or suspected human brucellosis where agglutination and/or complement fixation tests were positive, and in 21 sera negative to conventional tests. H demonstreated remote or undiagnosed human B. abortus infections in 28.6 per cent of 18 367 human sera randomly examined in a rural area. Therefore, a simple easy-to-perform passive hemagglutination test could replace a battery of conventional tests for the diagnosis of individual brucellosis, and epidemiologic surveys. The present study points to a high prevalence of undiagnosed brucellosis in man, specially in those area where cattle are raised."}
{"id": "PMID:219487", "title": "[Hemoglobinopathies in West-African immigrant workers in France (author's transl)].", "content": "In this paper are brought the results obtained in two Parisian hospitals during a survey of abnormal hemoglobins in 540 immigrant workers coming from Africa, mostly from Mali, Mauritania and Senegal. All the subjects investigated were male and between 20 and 40 years old. The studies were performed following internationally standardized technics. The most frequent abnormalities were: Hb S found in 16.3%, Hb C (6.6%), alpha-thalassemia trait (3.1%) and beta-thalassemia trait (3.1%). Some rare abnormalities were also found: delta-chain variants, hereditary persistance of foetal hemoglobin, Hb Hope and Hb Grady. This work emphasizes the high frequency of the different hemoglobin disorders in this population. The easy diagnostic of electrophoretically detectable variants is compared to the more complex situation of thalassemia leading probably to an under estimation of the percentage.", "contents": "[Hemoglobinopathies in West-African immigrant workers in France (author's transl)]. In this paper are brought the results obtained in two Parisian hospitals during a survey of abnormal hemoglobins in 540 immigrant workers coming from Africa, mostly from Mali, Mauritania and Senegal. All the subjects investigated were male and between 20 and 40 years old. The studies were performed following internationally standardized technics. The most frequent abnormalities were: Hb S found in 16.3%, Hb C (6.6%), alpha-thalassemia trait (3.1%) and beta-thalassemia trait (3.1%). Some rare abnormalities were also found: delta-chain variants, hereditary persistance of foetal hemoglobin, Hb Hope and Hb Grady. This work emphasizes the high frequency of the different hemoglobin disorders in this population. The easy diagnostic of electrophoretically detectable variants is compared to the more complex situation of thalassemia leading probably to an under estimation of the percentage."}
{"id": "PMID:219484", "title": "[Splenic lympho-plasmocytic sarcomas discovered by exploratory laparotomy in 2 cases of cold agglutinin disease].", "content": "The 2 patients have cold agglutinin disease with lymphoid nodules in the bone marrow. A splenectomy was done because of the severity of the hemolytic anemia and because of the increasing splenomegaly. Tumoral nodules with the aspect of lymphoplasmocytic sarcoma or immunocytoma were discovered in the spleen. Those tumors can be considered either as a morphologic aspect of the cold agglutinin disease which is yet considered as a kind of chronic lymphoproliferative syndrom or as the proliferation of an other clone. In this hypothesis, the lymphoplasmocytic sarcoma habe the same signification that the Richter's syndrome in chronic lymphoid leukemia and that the sarcoma appearing in Waldenstr\u00f6m's macroglobulinemia or in alpha heavy chain disease.", "contents": "[Splenic lympho-plasmocytic sarcomas discovered by exploratory laparotomy in 2 cases of cold agglutinin disease]. The 2 patients have cold agglutinin disease with lymphoid nodules in the bone marrow. A splenectomy was done because of the severity of the hemolytic anemia and because of the increasing splenomegaly. Tumoral nodules with the aspect of lymphoplasmocytic sarcoma or immunocytoma were discovered in the spleen. Those tumors can be considered either as a morphologic aspect of the cold agglutinin disease which is yet considered as a kind of chronic lymphoproliferative syndrom or as the proliferation of an other clone. In this hypothesis, the lymphoplasmocytic sarcoma habe the same signification that the Richter's syndrome in chronic lymphoid leukemia and that the sarcoma appearing in Waldenstr\u00f6m's macroglobulinemia or in alpha heavy chain disease."}
{"id": "PMID:219488", "title": "[Pharmacokinetics and metabolism of sultopride in the dog. Qualitative and quantitative analysis in various organs].", "content": "After oral administration of a single dose of 45 mg/kg of sultopride in the dog, concentrations in different organs were determined after 1, 6 and 24 hours. Sultopride and his deethly metabolite have been identified and determined. The maximal concentration of the benzamides were found in the organs one hour after administration.", "contents": "[Pharmacokinetics and metabolism of sultopride in the dog. Qualitative and quantitative analysis in various organs]. After oral administration of a single dose of 45 mg/kg of sultopride in the dog, concentrations in different organs were determined after 1, 6 and 24 hours. Sultopride and his deethly metabolite have been identified and determined. The maximal concentration of the benzamides were found in the organs one hour after administration."}
{"id": "PMID:219489", "title": "[Systematic cardiologic study in 37 schistosomiasis patients].", "content": "1) A systematic search was made for cardiac abnormalities (clinical, radiological and EKG) and for haemodynamic disorders (catheterisation of the right side of the heart and pulmonary artery). It was generally found that: -- 14 patients (37.8%) had no symptoms; -- 8 patients (21.6%) had pulmonary arterial hypertension (PAHT) with the corresponding cardiac signs; -- 15 patients (40.5%) had cardiac signs with no evidence of PAHT. 2) The 8 patients with PAHT (21.6%) had precapillary type of PAHT with an arteriocapillary gradient. The symptoms were those of PAHT and of the right ventricular failure; but this desorder could be latent. PAHT can be in relation with inflammatory lesions. In these 8 patients, S. Mansoni was to blame in 6 cases and 5 S. Hematobium in 2. 3) In 9 patients (24.3%), cardiac signs were connected indirectly with bilharziasis by anemia, iatrogenic injury or hypertensive myocardial disease of renal origin. 4) In 3 patients (8.1%), cardiac signs were found because of coexistant disease. 5) In 3 patients (8.1%), cardiac signs could have been due to bilharzia myocarditis. The authors reviewed the experimental and clinical discussions for such a possibility.", "contents": "[Systematic cardiologic study in 37 schistosomiasis patients]. 1) A systematic search was made for cardiac abnormalities (clinical, radiological and EKG) and for haemodynamic disorders (catheterisation of the right side of the heart and pulmonary artery). It was generally found that: -- 14 patients (37.8%) had no symptoms; -- 8 patients (21.6%) had pulmonary arterial hypertension (PAHT) with the corresponding cardiac signs; -- 15 patients (40.5%) had cardiac signs with no evidence of PAHT. 2) The 8 patients with PAHT (21.6%) had precapillary type of PAHT with an arteriocapillary gradient. The symptoms were those of PAHT and of the right ventricular failure; but this desorder could be latent. PAHT can be in relation with inflammatory lesions. In these 8 patients, S. Mansoni was to blame in 6 cases and 5 S. Hematobium in 2. 3) In 9 patients (24.3%), cardiac signs were connected indirectly with bilharziasis by anemia, iatrogenic injury or hypertensive myocardial disease of renal origin. 4) In 3 patients (8.1%), cardiac signs were found because of coexistant disease. 5) In 3 patients (8.1%), cardiac signs could have been due to bilharzia myocarditis. The authors reviewed the experimental and clinical discussions for such a possibility."}
{"id": "PMID:219491", "title": "[Results of a national therapeutic trial in 10,000 hypertensive patients conducted by 2000 general practitioners (author's transl)].", "content": "Multicenter study in 10294 hypertensive patients conducted by 2000 G.P.'s throughout France. This trial permitted to compare the effectiveness and tolerance of 3 types of antihypertensive therapy: a beta-blocker, a diuretic and a central antihypertensive agent. It also permitted to study a certain number of socio-epidemiological characteristics in that patient population, in particular with regard to cardio-vascular risk factors.", "contents": "[Results of a national therapeutic trial in 10,000 hypertensive patients conducted by 2000 general practitioners (author's transl)]. Multicenter study in 10294 hypertensive patients conducted by 2000 G.P.'s throughout France. This trial permitted to compare the effectiveness and tolerance of 3 types of antihypertensive therapy: a beta-blocker, a diuretic and a central antihypertensive agent. It also permitted to study a certain number of socio-epidemiological characteristics in that patient population, in particular with regard to cardio-vascular risk factors."}
{"id": "PMID:219490", "title": "[Tolerance and short-term results of the systematic laparotomy-chemotherapy-radiotherapy sequence in Hodgkin's disease in adults].", "content": "Twenty five cases of Hodgkin disease were treated by chemotherapy and radiotherapy after staging laparotomy. The safety and the utility of staging laparotomy are discussed. Staging laparotomy seems to be usefull in stage II with involvement of at least three lymphatic territories and in stage III.", "contents": "[Tolerance and short-term results of the systematic laparotomy-chemotherapy-radiotherapy sequence in Hodgkin's disease in adults]. Twenty five cases of Hodgkin disease were treated by chemotherapy and radiotherapy after staging laparotomy. The safety and the utility of staging laparotomy are discussed. Staging laparotomy seems to be usefull in stage II with involvement of at least three lymphatic territories and in stage III."}
{"id": "PMID:219492", "title": "[Treatment of headache in neuro-radiological investigations (author's transl)].", "content": "The aim of this study was to try the efficiency of tiapridal in preventing headache during neuro-radiological procedures. In spite of indiscutable curative effect, this drug does not prove to be efficient in preventive effect. The authors described a new protocol using IV infusion at the end of the radiological procedure, followed by pills per os. No side effect was observed.", "contents": "[Treatment of headache in neuro-radiological investigations (author's transl)]. The aim of this study was to try the efficiency of tiapridal in preventing headache during neuro-radiological procedures. In spite of indiscutable curative effect, this drug does not prove to be efficient in preventive effect. The authors described a new protocol using IV infusion at the end of the radiological procedure, followed by pills per os. No side effect was observed."}
{"id": "PMID:219493", "title": "[Does mastoiditis still exist? (author's transl)].", "content": "The authors report 382 cases of mastoidectomy verified by histological examination and draw certain conclusions: There were 5 errors in diagnosis, i.e. 1.3 per cent. Most cases were aged between 4 and 12 months. Below the age of two years it was usually bilateral, exceptionally so after the age of two years. Diagnosis was mainly clinical and based on the following axiom: \"All infants with acute otitis who, in spite of proper medical treatment, have at the end of one month of a weight curve either stationary or falling, and eardrums not strictly normal, have mastoiditis\". This therefore implies close and prolonged supervision by the same observer throughout the period antibiotic treatment and at least one week after stopping the latter. The treatment is still mastoidectomy and not antrotomy but one may hope with more accurate diagnosis that new methods of treatment may be developed to the extent where immediate and long term supervision of the child may be ensured.", "contents": "[Does mastoiditis still exist? (author's transl)]. The authors report 382 cases of mastoidectomy verified by histological examination and draw certain conclusions: There were 5 errors in diagnosis, i.e. 1.3 per cent. Most cases were aged between 4 and 12 months. Below the age of two years it was usually bilateral, exceptionally so after the age of two years. Diagnosis was mainly clinical and based on the following axiom: \"All infants with acute otitis who, in spite of proper medical treatment, have at the end of one month of a weight curve either stationary or falling, and eardrums not strictly normal, have mastoiditis\". This therefore implies close and prolonged supervision by the same observer throughout the period antibiotic treatment and at least one week after stopping the latter. The treatment is still mastoidectomy and not antrotomy but one may hope with more accurate diagnosis that new methods of treatment may be developed to the extent where immediate and long term supervision of the child may be ensured."}
{"id": "PMID:219494", "title": "[The child's gastroduodenal ulcer (author's transl)].", "content": "The child's gastroduodenal ulcer is not uncommon. Its symptomatology is notably different from the adult's and gives it a rather original aspect. The pain is often atypical, almost permanent and its rythm is not necessarily related to the meals. The psychological context and the family background are almost always disclosed. The digestive hemorrhage is easily revealing. Radiological traps are to be known. The treatment is virtually always medical. Cimetidine has been used only in complications, in which it has appeared very useful. Surgery is not called for but in case of perforation or hemorrhage; then it is essentially preserving.", "contents": "[The child's gastroduodenal ulcer (author's transl)]. The child's gastroduodenal ulcer is not uncommon. Its symptomatology is notably different from the adult's and gives it a rather original aspect. The pain is often atypical, almost permanent and its rythm is not necessarily related to the meals. The psychological context and the family background are almost always disclosed. The digestive hemorrhage is easily revealing. Radiological traps are to be known. The treatment is virtually always medical. Cimetidine has been used only in complications, in which it has appeared very useful. Surgery is not called for but in case of perforation or hemorrhage; then it is essentially preserving."}
{"id": "PMID:219495", "title": "[Long survival periods after therapy for metastatic or reccurrent cancer (author's transl)].", "content": "Out of 671 cases of various cancers, first seen for growing metastases and or recurrences (resectable cases being excluded) the 3 years survival rate has been 18 per cent (121 cases). This result was obtained by various combinations of chemotherapy and radiotherapy. It follows that advanced cases should not be abandoned without any attempt at control, and that earlier treatments in cases being at high risk for metastases would probably further increase such results.", "contents": "[Long survival periods after therapy for metastatic or reccurrent cancer (author's transl)]. Out of 671 cases of various cancers, first seen for growing metastases and or recurrences (resectable cases being excluded) the 3 years survival rate has been 18 per cent (121 cases). This result was obtained by various combinations of chemotherapy and radiotherapy. It follows that advanced cases should not be abandoned without any attempt at control, and that earlier treatments in cases being at high risk for metastases would probably further increase such results."}
{"id": "PMID:219497", "title": "[Costal echinococcosis. Report of one case and review of the literature (author's transl)].", "content": "Following the report of a case of costal echinococcosis, a review of the published literature showed that 32 identical cases have been the subject of publications in the Occident. A further 6 cases were found in the records of the University Hospitals in Teheran, which brings the total to 39 published cases, including our patient, known at the present time. It is important to make the diagnosis in these cases so that the surgeon can take the necessary precautions to avoid the anaphylactic shock which can follow dissemination of the parasite.", "contents": "[Costal echinococcosis. Report of one case and review of the literature (author's transl)]. Following the report of a case of costal echinococcosis, a review of the published literature showed that 32 identical cases have been the subject of publications in the Occident. A further 6 cases were found in the records of the University Hospitals in Teheran, which brings the total to 39 published cases, including our patient, known at the present time. It is important to make the diagnosis in these cases so that the surgeon can take the necessary precautions to avoid the anaphylactic shock which can follow dissemination of the parasite."}
{"id": "PMID:219498", "title": "[Bilateral breast localization of Kahler's disease: cytological and histological aspects].", "content": "Breast localisation of multiple myeloma is quite unfrequent. In one case of a 69 years old man, the diagnosis was suspected by a cytological aspiration biopsy of the lesion, and later confirmed by histological and biological investigations. The analysis of the literature has enabled the authors to gather 7 other cases and to describe the characters of this peculiar tumoral localisation. The breast involvement is mostly observed in women. The average is 38 years old. Only 2 cases deal with men, both treated with estrogens. The lesion is usually bilateral and nearly always associated with other visceral and bone localisations. It is not modified by chemiotherapy and appears shortly before death.", "contents": "[Bilateral breast localization of Kahler's disease: cytological and histological aspects]. Breast localisation of multiple myeloma is quite unfrequent. In one case of a 69 years old man, the diagnosis was suspected by a cytological aspiration biopsy of the lesion, and later confirmed by histological and biological investigations. The analysis of the literature has enabled the authors to gather 7 other cases and to describe the characters of this peculiar tumoral localisation. The breast involvement is mostly observed in women. The average is 38 years old. Only 2 cases deal with men, both treated with estrogens. The lesion is usually bilateral and nearly always associated with other visceral and bone localisations. It is not modified by chemiotherapy and appears shortly before death."}
{"id": "PMID:219499", "title": "[Plasma cell granuloma of the lung. Report of two cases (author's transl)].", "content": "The authors report two cases of inflammatory pseudotumour of the lung, one discovered by chance in a 15 year old boy and the other following a hemoptysis in a 48 year old man. In both cases, the granuloma was mainly fibroblastic but also included lymphocytes and plasma cells, macrophages and mast cells. The histology, age of onset, the sex and the pulmonary localisations are different for plasma cell granulomas and fibrosing hemangiomas.", "contents": "[Plasma cell granuloma of the lung. Report of two cases (author's transl)]. The authors report two cases of inflammatory pseudotumour of the lung, one discovered by chance in a 15 year old boy and the other following a hemoptysis in a 48 year old man. In both cases, the granuloma was mainly fibroblastic but also included lymphocytes and plasma cells, macrophages and mast cells. The histology, age of onset, the sex and the pulmonary localisations are different for plasma cell granulomas and fibrosing hemangiomas."}
{"id": "PMID:219496", "title": "[Athletic activities and prevention of vascular risk factors].", "content": "Vascular accidents represent one of the most important causes of morbidity and mortality in France at the present time, and factors increasing the risk of such lesions are well documented: hypertension, smoking, and metabolic disorders (lipids, glucides, uric acid). Though genetic factors are definitely involved, most of them are acquired and related to our way of life, our type of civilisation, and, more particularly, to overeating and a sedentary life. Regular physical exercise of sufficient degree can considerably reduce the various factors which increase risk and, at the same time, diminish the frequency of these very serious vascular accidents.", "contents": "[Athletic activities and prevention of vascular risk factors]. Vascular accidents represent one of the most important causes of morbidity and mortality in France at the present time, and factors increasing the risk of such lesions are well documented: hypertension, smoking, and metabolic disorders (lipids, glucides, uric acid). Though genetic factors are definitely involved, most of them are acquired and related to our way of life, our type of civilisation, and, more particularly, to overeating and a sedentary life. Regular physical exercise of sufficient degree can considerably reduce the various factors which increase risk and, at the same time, diminish the frequency of these very serious vascular accidents."}
{"id": "PMID:219500", "title": "[Treatment of duodenal ulcers with antacid mixtures and sulpiride. A double-blind controlled study (author's transl)].", "content": "A total of 108 patients with duodenal ulcers were divided into 4 groups in a double-blind study controlled by endoscopic examinations. Patients in each group were given either an antacid mixture or sulpiride alone, antacid mixture plus sulpiride, or a placebo. The highest complete recovery rate (84 per cent) was noted in the antacid mixture plus sulpiride group, while partial healing (more than 50 per cent reduction in ulcer size) was highest in the sulpiride group (84,6 per cent). As sulpiride has both healing effects on the ulcer and an analgesic effect against pain it can be prescribed in association with antacid mixtures for the treatment of duodenal ulcers.", "contents": "[Treatment of duodenal ulcers with antacid mixtures and sulpiride. A double-blind controlled study (author's transl)]. A total of 108 patients with duodenal ulcers were divided into 4 groups in a double-blind study controlled by endoscopic examinations. Patients in each group were given either an antacid mixture or sulpiride alone, antacid mixture plus sulpiride, or a placebo. The highest complete recovery rate (84 per cent) was noted in the antacid mixture plus sulpiride group, while partial healing (more than 50 per cent reduction in ulcer size) was highest in the sulpiride group (84,6 per cent). As sulpiride has both healing effects on the ulcer and an analgesic effect against pain it can be prescribed in association with antacid mixtures for the treatment of duodenal ulcers."}
{"id": "PMID:219501", "title": "[Complete atrio-ventricular block caused by a metastatic tumor of the heart. Apropos of a case].", "content": "Metastatic tumors of the heart are often asymptomatic but they may dominate the clinical picture. The location in the interventricular septum can account for conduction disturbances. The authors report a case of esophagus neoplasm with septal metastasis responsible for a complete atrioventricular block. The histologic study of the bundle of His by serial sections showing the destruction of the conduction fibres by malignant elements has not been carried out till now except in some observations. The prognostic of the atrioventricular metastatic block is very poor; the ten months' survival which was observed in the reported case is one of the most extended in literature.", "contents": "[Complete atrio-ventricular block caused by a metastatic tumor of the heart. Apropos of a case]. Metastatic tumors of the heart are often asymptomatic but they may dominate the clinical picture. The location in the interventricular septum can account for conduction disturbances. The authors report a case of esophagus neoplasm with septal metastasis responsible for a complete atrioventricular block. The histologic study of the bundle of His by serial sections showing the destruction of the conduction fibres by malignant elements has not been carried out till now except in some observations. The prognostic of the atrioventricular metastatic block is very poor; the ten months' survival which was observed in the reported case is one of the most extended in literature."}
{"id": "PMID:219502", "title": "[Hyperthyroidism and atrioventricular heart block (author's transl)].", "content": "Two cases of thyrotoxicosis including a first-degree heart block are reported; a study of action potentials of the bundle of His was achieved in the second case. The association atrioventricular block-hyperthyroidism is unusual but does not seem to be a pure coincidence. The direct effect of thyroid hormon on the myocardium is supposed to be responsible for the conduction disturbance; its disappearance with the cure of the thyrotoxicosis is a favourable argument for a relation of causality. The therapeutic consequence of this association is to exclude completely the use of betablockers.", "contents": "[Hyperthyroidism and atrioventricular heart block (author's transl)]. Two cases of thyrotoxicosis including a first-degree heart block are reported; a study of action potentials of the bundle of His was achieved in the second case. The association atrioventricular block-hyperthyroidism is unusual but does not seem to be a pure coincidence. The direct effect of thyroid hormon on the myocardium is supposed to be responsible for the conduction disturbance; its disappearance with the cure of the thyrotoxicosis is a favourable argument for a relation of causality. The therapeutic consequence of this association is to exclude completely the use of betablockers."}
{"id": "PMID:219503", "title": "[Williams-Beuren syndrome and renovascular arterial hypertension].", "content": "The Williams and Beuren's syndrome associates a particuliar facies, a mental debility, a supravalvular aortic stenosis, and frequent vascular anomalies of pulmonary artery as well as  aorta and its branches. Relations between this syndrome and congenital idiopathic hypercalcemia seem now determined; the hypertension which has been frequently observed in this last case, seems more unusual in the case of Williams and Beuren's syndrome. The authors report a case about this syndrome in which the hypertension seemed linked to a stenosis of the left renal artery and which has been treated surgically. A year later the result is satisfactory but the evolutive potential of arterial lesions described in this syndrome does not necessory lead to a final recovery. Besides there are in this disease hypertensions which are relevant to an other etiology (more especially aortic hypoplasia) and stenosis of renal arteries without hypertension.", "contents": "[Williams-Beuren syndrome and renovascular arterial hypertension]. The Williams and Beuren's syndrome associates a particuliar facies, a mental debility, a supravalvular aortic stenosis, and frequent vascular anomalies of pulmonary artery as well as  aorta and its branches. Relations between this syndrome and congenital idiopathic hypercalcemia seem now determined; the hypertension which has been frequently observed in this last case, seems more unusual in the case of Williams and Beuren's syndrome. The authors report a case about this syndrome in which the hypertension seemed linked to a stenosis of the left renal artery and which has been treated surgically. A year later the result is satisfactory but the evolutive potential of arterial lesions described in this syndrome does not necessory lead to a final recovery. Besides there are in this disease hypertensions which are relevant to an other etiology (more especially aortic hypoplasia) and stenosis of renal arteries without hypertension."}
{"id": "PMID:219504", "title": "[Horseshoe kidney and hypertension (author's transl)].", "content": "The authors report a case of horseshoe kidney responsible for hypertension through a one-sided renal dysplasia. The part of the renal malformation in the development of the hypertension is attested by the activities of renin from renal veins, by the isotopic nephrogram and by the disappearance of the hypertension following the heminephrectomy. The hypertension seems an exceptionnal complication of the horseshoe kidney, which can be surprising given the frequency of this malformation and associated urologic anomalies.", "contents": "[Horseshoe kidney and hypertension (author's transl)]. The authors report a case of horseshoe kidney responsible for hypertension through a one-sided renal dysplasia. The part of the renal malformation in the development of the hypertension is attested by the activities of renin from renal veins, by the isotopic nephrogram and by the disappearance of the hypertension following the heminephrectomy. The hypertension seems an exceptionnal complication of the horseshoe kidney, which can be surprising given the frequency of this malformation and associated urologic anomalies."}
{"id": "PMID:219505", "title": "[Carcinoma in situ of the bladder. Apropos of 10 cases].", "content": "10 cases of primary carcinoma in situ are described and the symptomatology of the disease is analysed. The role of cytodiagnosis is emphasised. The evolution is variable. In  2 cases the bladder became totally retracted and total cystectomy had to be performed in spite of the fact that the lesion remained intra-urothelial. Invasive cancer developped only in 2 cases: 7 and 6 years after diagnosis. Conservative treatment by Tur seems logical whilst the carcinoma remains strictly \"in situ\".", "contents": "[Carcinoma in situ of the bladder. Apropos of 10 cases]. 10 cases of primary carcinoma in situ are described and the symptomatology of the disease is analysed. The role of cytodiagnosis is emphasised. The evolution is variable. In  2 cases the bladder became totally retracted and total cystectomy had to be performed in spite of the fact that the lesion remained intra-urothelial. Invasive cancer developped only in 2 cases: 7 and 6 years after diagnosis. Conservative treatment by Tur seems logical whilst the carcinoma remains strictly \"in situ\"."}
{"id": "PMID:219506", "title": "[Strangulated or impacted diaphragmatic hernias. Treatment of six cases (author's transl)].", "content": "The authors report the cure of six recent cases of strangulated or impacted diaphragmatic hernia: 3 post-traumatic, 2 hiatal, one congenital. Strangulation or simple impaction are responsible for ischemic phenomena with necrosis and intrathoracic visceral perforation. Intensive care for respiratory, cardio-vascular and metabolic complications, including gastric aspiration, has transformed the prognosis which was recently so poor in this condition. The thoracic approach is advised for the usual reasons and owing to frequent intrathoracic adhesions. It is also advised for ease of treatment of the strangulated viscus and local septic complications.", "contents": "[Strangulated or impacted diaphragmatic hernias. Treatment of six cases (author's transl)]. The authors report the cure of six recent cases of strangulated or impacted diaphragmatic hernia: 3 post-traumatic, 2 hiatal, one congenital. Strangulation or simple impaction are responsible for ischemic phenomena with necrosis and intrathoracic visceral perforation. Intensive care for respiratory, cardio-vascular and metabolic complications, including gastric aspiration, has transformed the prognosis which was recently so poor in this condition. The thoracic approach is advised for the usual reasons and owing to frequent intrathoracic adhesions. It is also advised for ease of treatment of the strangulated viscus and local septic complications."}
{"id": "PMID:219507", "title": "[Contraception in diabetic women (author's transl)].", "content": "Contraception in diabetic women is necessary in order to plane pregnancies. Patients with chemical diabetes or family story of diabetes, babys with birth's weight over four kilogrammes, pregnancy's diabetes, may not use oestroprogestative pills. In this group progestins minipills can be used. Insulin-treated women may use oestroprogestative minipills as well as progestins minipills. In both groups, metabolic-controls must be performed every three months. It is also necessary to look at the funduns regarding to the unknown effects of contraceptives on diabetic microangiopathy. One or more other contrindication to oral contraceptives obliged to use intra-uterine device.", "contents": "[Contraception in diabetic women (author's transl)]. Contraception in diabetic women is necessary in order to plane pregnancies. Patients with chemical diabetes or family story of diabetes, babys with birth's weight over four kilogrammes, pregnancy's diabetes, may not use oestroprogestative pills. In this group progestins minipills can be used. Insulin-treated women may use oestroprogestative minipills as well as progestins minipills. In both groups, metabolic-controls must be performed every three months. It is also necessary to look at the funduns regarding to the unknown effects of contraceptives on diabetic microangiopathy. One or more other contrindication to oral contraceptives obliged to use intra-uterine device."}
{"id": "PMID:219508", "title": "[Study of 52 cases of diphtheria observed over a period of ten years in the North of France (author's transl)].", "content": "Over a period of ten years, 88 cases of diphtheria were diagnosed in the North of France especially in the area of Lille, Roubaix and Tourcoing. 25 p. cent of the patients had been correctly vaccinated within less than five years, and among the latter 25 p. cent died from their diphtheria. The clinical presentation was typical but delay in diagnosis is frequent.", "contents": "[Study of 52 cases of diphtheria observed over a period of ten years in the North of France (author's transl)]. Over a period of ten years, 88 cases of diphtheria were diagnosed in the North of France especially in the area of Lille, Roubaix and Tourcoing. 25 p. cent of the patients had been correctly vaccinated within less than five years, and among the latter 25 p. cent died from their diphtheria. The clinical presentation was typical but delay in diagnosis is frequent."}
{"id": "PMID:219509", "title": "[Value of the timolol-hydrochlorothiazide-amiloride hydrochloride combination in the mass treatment of arterial hypertension. Results of a multinational study].", "content": "In a 10-week double-blind study, 283 hypertensive patients were treated with a beta-blocker (timolol) alone, a combination of two diuretics (hydrochlorothiazide + amiloride) or a combination of both types of treatment. The results on blood pressure figures were very much in favor of the combination therapy as compared to monotherapy. In a second step, the trial was unblinded and all patients continued with the beta-blocker/diuretic combination for a total of 24 weeks. The medium-term results confirmed those obtained during the double-blind study with regard to the effectiveness and good tolerance of the combination treatment.", "contents": "[Value of the timolol-hydrochlorothiazide-amiloride hydrochloride combination in the mass treatment of arterial hypertension. Results of a multinational study]. In a 10-week double-blind study, 283 hypertensive patients were treated with a beta-blocker (timolol) alone, a combination of two diuretics (hydrochlorothiazide + amiloride) or a combination of both types of treatment. The results on blood pressure figures were very much in favor of the combination therapy as compared to monotherapy. In a second step, the trial was unblinded and all patients continued with the beta-blocker/diuretic combination for a total of 24 weeks. The medium-term results confirmed those obtained during the double-blind study with regard to the effectiveness and good tolerance of the combination treatment."}
{"id": "PMID:219510", "title": "[Primary hyperparathyroidism. Current aspects of its diagnosis apropos of a case with digestive and neuropsychiatric manifestations].", "content": "On the basis of a dramatic hypercalcemia revealed by digestive and neuropsychic symptoms and related to a primary hyperparathyroidism, the authors recall all the clinical circumstances which should lead to determination of plasma calcium as well as the clinical and biological particularities which, in front of a hypercalcemia, suggest a primary hyperparathyroidism. The stress the usefulness and the limits of the dosage of plasma immunoreactive parathyroid hormone as well as the difficulties to differentiale primary from paraneoplasic hyperparathyroidism. The recent pathophysiological concepts of malignant hypercalcemia reviewed.", "contents": "[Primary hyperparathyroidism. Current aspects of its diagnosis apropos of a case with digestive and neuropsychiatric manifestations]. On the basis of a dramatic hypercalcemia revealed by digestive and neuropsychic symptoms and related to a primary hyperparathyroidism, the authors recall all the clinical circumstances which should lead to determination of plasma calcium as well as the clinical and biological particularities which, in front of a hypercalcemia, suggest a primary hyperparathyroidism. The stress the usefulness and the limits of the dosage of plasma immunoreactive parathyroid hormone as well as the difficulties to differentiale primary from paraneoplasic hyperparathyroidism. The recent pathophysiological concepts of malignant hypercalcemia reviewed."}
{"id": "PMID:219511", "title": "[Hypopituitarism in the aged. Report of a case revealed by hypoglycemic coma (author's transl)].", "content": "The diagnosis of anterior pituitary insufficiency is difficult in the elderly and frequently made when the patient become comatose. At this age hypoglycemia is rarely the exclusive factor of this coma. The authors report a case revealed by hypoglycemic coma and supported by the lack of stimulation by the releasing factors. None etiology was found. With hormone treatment the patient recovered a normal life.", "contents": "[Hypopituitarism in the aged. Report of a case revealed by hypoglycemic coma (author's transl)]. The diagnosis of anterior pituitary insufficiency is difficult in the elderly and frequently made when the patient become comatose. At this age hypoglycemia is rarely the exclusive factor of this coma. The authors report a case revealed by hypoglycemic coma and supported by the lack of stimulation by the releasing factors. None etiology was found. With hormone treatment the patient recovered a normal life."}
{"id": "PMID:219513", "title": "[Remarks about twelve cases of pneumococcal septicemias (author's transl)].", "content": "Twelve cases of pneumococcal septicemias are studied in a department of internal medicine. These septicemias involved pneumonias often large, multilobular and bilateral, with often pleural effusion purulent or not and in one occurrence meningitis. There was three deaths by acute respiratory failure in one case of liver cirrhosis and in another case of chronic lymphocytic leukemia. Conditions of antibiotherapy and possible intensive care are discussed, prognosis factors as splenic insufficiency (in sickle cell anemia and after splenectomy) and immune defense against pneuococcus are recalled.", "contents": "[Remarks about twelve cases of pneumococcal septicemias (author's transl)]. Twelve cases of pneumococcal septicemias are studied in a department of internal medicine. These septicemias involved pneumonias often large, multilobular and bilateral, with often pleural effusion purulent or not and in one occurrence meningitis. There was three deaths by acute respiratory failure in one case of liver cirrhosis and in another case of chronic lymphocytic leukemia. Conditions of antibiotherapy and possible intensive care are discussed, prognosis factors as splenic insufficiency (in sickle cell anemia and after splenectomy) and immune defense against pneuococcus are recalled."}
{"id": "PMID:219514", "title": "[Lymphography in tuberculosis in black African immigrants].", "content": "Lymphographic data in 23 negro immigrants with lymph nodes tuberculosis almost always mediastinal and/or superficial are reported. In six cases, including two cases with abdominal latero-aortic lymph nodes clinically obvious, lymphography showed abnormalities without doubt. These aspects are compared with data of literature and discussed according to interpretation and significance in tuberculosis very peculiar in negro immigrants.20", "contents": "[Lymphography in tuberculosis in black African immigrants]. Lymphographic data in 23 negro immigrants with lymph nodes tuberculosis almost always mediastinal and/or superficial are reported. In six cases, including two cases with abdominal latero-aortic lymph nodes clinically obvious, lymphography showed abnormalities without doubt. These aspects are compared with data of literature and discussed according to interpretation and significance in tuberculosis very peculiar in negro immigrants.20"}
{"id": "PMID:219515", "title": "[Laparoscopy in black African immigrants. Apropos of 60 cases].", "content": "Authors give results about 60 laparoscopies in negro immigrants. If one excepts isolated cases of liver cirrhosis, hepatoma, staphylococcic liver abscess, lymphosarcoma or schistosomiasis of the peritoneum and twelve normal laparoscopies, the most frequent diagnosis in this peculiar group is peritoneal and/or liver tuberculosis (21 cases). Endoscopic aspects of hepato-splenic schistosomiasis are summarized. Interest of liver and/or peritoneal biopsies is underlined. Problem of liver granulomatosis may be ambiguous between schistosomiasis and tuberculosis.", "contents": "[Laparoscopy in black African immigrants. Apropos of 60 cases]. Authors give results about 60 laparoscopies in negro immigrants. If one excepts isolated cases of liver cirrhosis, hepatoma, staphylococcic liver abscess, lymphosarcoma or schistosomiasis of the peritoneum and twelve normal laparoscopies, the most frequent diagnosis in this peculiar group is peritoneal and/or liver tuberculosis (21 cases). Endoscopic aspects of hepato-splenic schistosomiasis are summarized. Interest of liver and/or peritoneal biopsies is underlined. Problem of liver granulomatosis may be ambiguous between schistosomiasis and tuberculosis."}
{"id": "PMID:219516", "title": "[Optic neuritis and sarcoidosis (author's transl)].", "content": "Case report of a sarcoidosis in a young west-indies feurale: ganglio-mediastinal and lung lesions, liver and salivary glands right optic nerve with retrobulbar optic neuritis. This lesions were quickly and totally reversible with tetracosactide and prednisone therapy.", "contents": "[Optic neuritis and sarcoidosis (author's transl)]. Case report of a sarcoidosis in a young west-indies feurale: ganglio-mediastinal and lung lesions, liver and salivary glands right optic nerve with retrobulbar optic neuritis. This lesions were quickly and totally reversible with tetracosactide and prednisone therapy."}
{"id": "PMID:219517", "title": "[Pleural biopsy: benefits of a new needle (author's transl)].", "content": "Authors compare results shown by Abrams needle and a new needle in pleural biopsies. With the new needle, Abrams-derived, out of 102 biopsies, there are 30 percent of unquestionable diagnosis and 10 percent of failure, though handlers were not in training. These results are statistically significant better than those of 244 biopsies with Abrams needle and recorded by the same pathologist (M.J.). They are comparable with those of handlers well trained.", "contents": "[Pleural biopsy: benefits of a new needle (author's transl)]. Authors compare results shown by Abrams needle and a new needle in pleural biopsies. With the new needle, Abrams-derived, out of 102 biopsies, there are 30 percent of unquestionable diagnosis and 10 percent of failure, though handlers were not in training. These results are statistically significant better than those of 244 biopsies with Abrams needle and recorded by the same pathologist (M.J.). They are comparable with those of handlers well trained."}
{"id": "PMID:219518", "title": "[Spontaneous perirenal hematoma in infants. Apropos of 2 cases].", "content": "The authors report two personal cases and note the special appearance of perirenal hematomas in infants. The pathogenesis is often obscure but this condition should be classified with the spontaneous perirenal hematomas and retroperitoneal tumour masses in infants.", "contents": "[Spontaneous perirenal hematoma in infants. Apropos of 2 cases]. The authors report two personal cases and note the special appearance of perirenal hematomas in infants. The pathogenesis is often obscure but this condition should be classified with the spontaneous perirenal hematomas and retroperitoneal tumour masses in infants."}
{"id": "PMID:219520", "title": "[Sacrococcygeal malformations: a report on 67 cases (author's transl)].", "content": "A series of 67 personal observations of sacrococcygeal malformation are reported, and these are reviewed together with the 249 cases in the published literature. The clinical picture and pathogenic mechanisms are discussed, and the frequent association of other congenital abnormalities, more particularly of the ano-rectal type, is stressed. The functional results obtained depend on the severity of the neurological lesions, associated malformations, and the quality of the treatments used.", "contents": "[Sacrococcygeal malformations: a report on 67 cases (author's transl)]. A series of 67 personal observations of sacrococcygeal malformation are reported, and these are reviewed together with the 249 cases in the published literature. The clinical picture and pathogenic mechanisms are discussed, and the frequent association of other congenital abnormalities, more particularly of the ano-rectal type, is stressed. The functional results obtained depend on the severity of the neurological lesions, associated malformations, and the quality of the treatments used."}
{"id": "PMID:219519", "title": "[The value of needle biopsy of the liver in the differential diagnosis of cholestatic jaundice. A clinico-pathologic study of 101 cases (author's transl)].", "content": "The examination of needle biopsy of the liver has permitted the identification of the aetiology of cholestatic jaundice in eighty five cases out of a series of one hundred-and-one patients, leaving eight without definite diagnosis and eight false diagnosis. The characteristic histopathologic lesions of lobular hepatitis and of obstructive jaundice are reviewed. The problems of identification of particular microscopic forms (obstructive jaundice with minimal portal tracts alterations, residual stage of hepatitis, cholangiolitic and hypercholestatic forms of hepatitis) are discussed.", "contents": "[The value of needle biopsy of the liver in the differential diagnosis of cholestatic jaundice. A clinico-pathologic study of 101 cases (author's transl)]. The examination of needle biopsy of the liver has permitted the identification of the aetiology of cholestatic jaundice in eighty five cases out of a series of one hundred-and-one patients, leaving eight without definite diagnosis and eight false diagnosis. The characteristic histopathologic lesions of lobular hepatitis and of obstructive jaundice are reviewed. The problems of identification of particular microscopic forms (obstructive jaundice with minimal portal tracts alterations, residual stage of hepatitis, cholangiolitic and hypercholestatic forms of hepatitis) are discussed."}
{"id": "PMID:219521", "title": "[Value of a new treatment of alcoholics in pneumology (author's transl)].", "content": "The efficiency and the tolerance of the tiapride have been studied in a group of 16 subjects. This new molecule help to treat the deficiency of alcohol without taking proceedings on the blood gas and without creation of a respiratory encephalopathy.", "contents": "[Value of a new treatment of alcoholics in pneumology (author's transl)]. The efficiency and the tolerance of the tiapride have been studied in a group of 16 subjects. This new molecule help to treat the deficiency of alcohol without taking proceedings on the blood gas and without creation of a respiratory encephalopathy."}
{"id": "PMID:219522", "title": "[Kinetics of bone uptake of 99m Tc-labeled diphosphonates. Preliminary results].", "content": "The bone fixation of diphosphonates depends on the degree of osteogenesis, the blood bone flow and the capillary permeability. The precise characteristics of the fixation kinetic are not very well known. The authors propose a new method which makes possible to study them and expose their results. For average persons the fixation curves present an ascending line, an apex, reach within 40 mn and a descending line. Any affection don't seem to have characteristic curves; on the contrary it is possible to have different curves for a same affection which implies doubtless various anatomic and metabolic data.", "contents": "[Kinetics of bone uptake of 99m Tc-labeled diphosphonates. Preliminary results]. The bone fixation of diphosphonates depends on the degree of osteogenesis, the blood bone flow and the capillary permeability. The precise characteristics of the fixation kinetic are not very well known. The authors propose a new method which makes possible to study them and expose their results. For average persons the fixation curves present an ascending line, an apex, reach within 40 mn and a descending line. Any affection don't seem to have characteristic curves; on the contrary it is possible to have different curves for a same affection which implies doubtless various anatomic and metabolic data."}
{"id": "PMID:219524", "title": "[Etiologic diagnosis of a digital necrosis: essential thrombocythemia. Review of the literature].", "content": "The author relates the disease of a man with a digital necrotizing in keeping with an excess of platelets. Clinical, biological and histological study may evolve diagnosis of idiopathic thrombocythemia. The check of concerned literature may specify profile of this disease which agree with platelet side of a myeloproliferative syndrome. Coagulation study is often disappointing but may involve interference of prostaglandins as an intimate mechanism for aggregation and adhesivity of platelets. Clinical course may very easily be supervised with standard medical treatment.", "contents": "[Etiologic diagnosis of a digital necrosis: essential thrombocythemia. Review of the literature]. The author relates the disease of a man with a digital necrotizing in keeping with an excess of platelets. Clinical, biological and histological study may evolve diagnosis of idiopathic thrombocythemia. The check of concerned literature may specify profile of this disease which agree with platelet side of a myeloproliferative syndrome. Coagulation study is often disappointing but may involve interference of prostaglandins as an intimate mechanism for aggregation and adhesivity of platelets. Clinical course may very easily be supervised with standard medical treatment."}
{"id": "PMID:219526", "title": "[Endocrine secretions by bronchial tumors].", "content": "Frequency of ectopic hormonal secretions by lung carcinomas is evaluated about 10 percent. Clinical and biological manifestations are less frequently registered than circulating hormonal products which can be considered as evolution markers of the disease. The main secretions and their clinical consequences are described: parathyroid hormone (PTH), calcitonin (CT), growth hormone (GH), antidiuretic hormone (ADH), corticotrophin hormone (ACTH) and gonadotrophins (HCG, LH, FSH). Problems raised by detection of these hormone-like acting products are studied and different hypothesis are suggested as explanation of these secretions.", "contents": "[Endocrine secretions by bronchial tumors]. Frequency of ectopic hormonal secretions by lung carcinomas is evaluated about 10 percent. Clinical and biological manifestations are less frequently registered than circulating hormonal products which can be considered as evolution markers of the disease. The main secretions and their clinical consequences are described: parathyroid hormone (PTH), calcitonin (CT), growth hormone (GH), antidiuretic hormone (ADH), corticotrophin hormone (ACTH) and gonadotrophins (HCG, LH, FSH). Problems raised by detection of these hormone-like acting products are studied and different hypothesis are suggested as explanation of these secretions."}
{"id": "PMID:219525", "title": "[A case of hemiballism].", "content": "When an hemiballism case occurs to a 73 year old patient having obtained few results of chlorpromazine, a tiapridal treatment is tried. First, by the means of an injection during twelve days, then by an oral way, the results are spectacular since the first week, without any disclosing secondary effect. In spite of an unperceivable shivering of both, the lower member and the right leg, the immediate results by tiapridal are further more positive, compared to those obtained by the neuroleptic treatments.", "contents": "[A case of hemiballism]. When an hemiballism case occurs to a 73 year old patient having obtained few results of chlorpromazine, a tiapridal treatment is tried. First, by the means of an injection during twelve days, then by an oral way, the results are spectacular since the first week, without any disclosing secondary effect. In spite of an unperceivable shivering of both, the lower member and the right leg, the immediate results by tiapridal are further more positive, compared to those obtained by the neuroleptic treatments."}
{"id": "PMID:219527", "title": "[Treatment of severe urinary infection in the elderly. Clinical and bacteriological study of 130 cases (author's transl)].", "content": "Strict criteria were applied in the choice of the 130 patients with severe urinary infections included in the study: men or women over 65 years of age presenting with clinical signs and symptoms, a bacterial count greater than or equal to 10(6)/mm3, one type of germ found on urine culture. The results of an antibiogram showed the frequency with which each germ was involved and their sensitivity to antibiotics, more particularly gentamicin, minocyclin, sulphamethoxazole-trimethoprime, oxolinic acid. Based on sensitivity and tolerance criteria, the choice of antibiotic was : oxolinic acid orally ; gentamicin parenterally, after evaluation of renal function. These results can assist the physician, when confronted with cases of severe urinary infection, and before the results of the antibiogram are available, in choosing effective therapy adapted to each case.", "contents": "[Treatment of severe urinary infection in the elderly. Clinical and bacteriological study of 130 cases (author's transl)]. Strict criteria were applied in the choice of the 130 patients with severe urinary infections included in the study: men or women over 65 years of age presenting with clinical signs and symptoms, a bacterial count greater than or equal to 10(6)/mm3, one type of germ found on urine culture. The results of an antibiogram showed the frequency with which each germ was involved and their sensitivity to antibiotics, more particularly gentamicin, minocyclin, sulphamethoxazole-trimethoprime, oxolinic acid. Based on sensitivity and tolerance criteria, the choice of antibiotic was : oxolinic acid orally ; gentamicin parenterally, after evaluation of renal function. These results can assist the physician, when confronted with cases of severe urinary infection, and before the results of the antibiogram are available, in choosing effective therapy adapted to each case."}
{"id": "PMID:219528", "title": "[Lipid particles agglutinated in hyperlipidemias with opalescent sera (author's transl)].", "content": "During the last five years, we observed under the microscope all the hyperlipidemic sera received in our laboratory, to search a lipid particle agglutination. We have retained 24 sera with obvious agglutination (9 types V, 9 types IV and 6 types IIb), the lipidemia of which was compared, type to type, to 56 control sera (16 types V, 16 types IV and 24 types IIb), in which no agglutination has been found. We observed significant differences in the means of cholesterol (CT) triglycerides (TG), vitamin A (VA) and CT/TG, VA/TG and VA/CT ratios, comparing agglutinated and control sera. These differences suggest that the agglutination phenomenon is in relation with the nature of the lipid particles present in the hyperlipidemic sera, which could be \"chylomicron remnants\" in type V hyperlipidemias, and other forms of \"remnants\" in type IV and IIb hyperlipidemias. These \"remnants\" could result from a blockade of lipolysis. This blockade of lipolysis in the agglutinated sera might be related to what is known about the authentificated autoimmune hyperlipidemia (AIH). Thus we can suppose that hyperlipidemias with obvious serum lipid particle agglutination are autoimmune hyperlipidemias.", "contents": "[Lipid particles agglutinated in hyperlipidemias with opalescent sera (author's transl)]. During the last five years, we observed under the microscope all the hyperlipidemic sera received in our laboratory, to search a lipid particle agglutination. We have retained 24 sera with obvious agglutination (9 types V, 9 types IV and 6 types IIb), the lipidemia of which was compared, type to type, to 56 control sera (16 types V, 16 types IV and 24 types IIb), in which no agglutination has been found. We observed significant differences in the means of cholesterol (CT) triglycerides (TG), vitamin A (VA) and CT/TG, VA/TG and VA/CT ratios, comparing agglutinated and control sera. These differences suggest that the agglutination phenomenon is in relation with the nature of the lipid particles present in the hyperlipidemic sera, which could be \"chylomicron remnants\" in type V hyperlipidemias, and other forms of \"remnants\" in type IV and IIb hyperlipidemias. These \"remnants\" could result from a blockade of lipolysis. This blockade of lipolysis in the agglutinated sera might be related to what is known about the authentificated autoimmune hyperlipidemia (AIH). Thus we can suppose that hyperlipidemias with obvious serum lipid particle agglutination are autoimmune hyperlipidemias."}
{"id": "PMID:219529", "title": "[Investigation of circulating immune complexes in some diseases associated with platelets hyperdestruction process (author's transl)].", "content": "A possible relationship between the presence of circulating immune complexes (CIC) and the platelet-bound IgG levels was investigated in 38 patients with some diseases associated with a no drug-related platelets hyperdestruction process of which 33 had idiopathic thrombopenic purpura (ITP). By using the 125I-C1q binding test, these CIC were only detected in 4 of the 42 tested sera. No correlation was noticed between the percentage of C1q binding and the platelet IgG levels evaluated by the quantitative hemolysis inhibition test. These results do not allow to consider the involvement of CIC in the thrombocytopenia genesis observed in these diseases.", "contents": "[Investigation of circulating immune complexes in some diseases associated with platelets hyperdestruction process (author's transl)]. A possible relationship between the presence of circulating immune complexes (CIC) and the platelet-bound IgG levels was investigated in 38 patients with some diseases associated with a no drug-related platelets hyperdestruction process of which 33 had idiopathic thrombopenic purpura (ITP). By using the 125I-C1q binding test, these CIC were only detected in 4 of the 42 tested sera. No correlation was noticed between the percentage of C1q binding and the platelet IgG levels evaluated by the quantitative hemolysis inhibition test. These results do not allow to consider the involvement of CIC in the thrombocytopenia genesis observed in these diseases."}
{"id": "PMID:219530", "title": "[Human cysticercosis. Four cases (First part) (author's transl)].", "content": "Produced by the larval form of Taenia solium, human cysticercosis is especially redoutable because of its great affinity for the nervous system and the eyes. In France, the isolated cases, apparently autochtons, are very seldom; cysticercosis is discovered, more frequently, among immigrated people. After an historical recall, the authors describe the lesions and, among clinical manifestations, the epileptogenic, ventricular and diffuse cerebral forms.", "contents": "[Human cysticercosis. Four cases (First part) (author's transl)]. Produced by the larval form of Taenia solium, human cysticercosis is especially redoutable because of its great affinity for the nervous system and the eyes. In France, the isolated cases, apparently autochtons, are very seldom; cysticercosis is discovered, more frequently, among immigrated people. After an historical recall, the authors describe the lesions and, among clinical manifestations, the epileptogenic, ventricular and diffuse cerebral forms."}
{"id": "PMID:219531", "title": "[Extraskeletal plasma cell tumors (author's transl)].", "content": "Extraskeletal plasmacytomas are very rare malignant plasma cell tumors. They often seem to arise from a pathologic plasma cell reaction to an antigenic stimulation and are characterized by the variety of their locations and the frequent absence of monoclonal dysproteinemia. The authors are reporting three new observations of extraskeletal plasma cell tumors. Some pathological, biological and pathogenic features of these tumors are emphasized.", "contents": "[Extraskeletal plasma cell tumors (author's transl)]. Extraskeletal plasmacytomas are very rare malignant plasma cell tumors. They often seem to arise from a pathologic plasma cell reaction to an antigenic stimulation and are characterized by the variety of their locations and the frequent absence of monoclonal dysproteinemia. The authors are reporting three new observations of extraskeletal plasma cell tumors. Some pathological, biological and pathogenic features of these tumors are emphasized."}
{"id": "PMID:219532", "title": "[Eosinophilia and respiratory function in the asthmatic (author's transl)].", "content": "Total eosinophil count (TEC) was done in 13 normal subjects, in 8 subjects before and 90 mn after a \"French\" breakfast and in 29 asthmatic patients. The geometric mean is higher (p less than 0,001) in asthmatic than in normal subjects: 304 (231--391) versus 144 (101--197). The breakfast does not interfer with the result of the TEC. In asthmatic subjects, a significant inverse correlation appears (r = 0,57, p less than 0,01) between the logarithm of TEC and the quotient: formula; see text. This correlation persists whatever may be the subject's age, the duration of the asthma or age at which he first contracted the illness. Asthma appeared after 40 years in 4 of the subjects: their TEC was higher (p less than 0,01) than in subjects who had become asthmatic before the age of forty. The respiratory function was lowered more in these 4 patients than in others who had been ill for the same time (p less than 0,001). The TEC is not related to results of skin testine with usuel inhalant allergens (grass pollen, house dust, cat's or dog's dander) or by result of a provocation test (by inhalation of allergen). Eosinophilia and bronchial obstruction are connected by one (or more) factors that may be inhalant allergens in extrinsec asthma and circulating immune complexes in intrinsec asthma.", "contents": "[Eosinophilia and respiratory function in the asthmatic (author's transl)]. Total eosinophil count (TEC) was done in 13 normal subjects, in 8 subjects before and 90 mn after a \"French\" breakfast and in 29 asthmatic patients. The geometric mean is higher (p less than 0,001) in asthmatic than in normal subjects: 304 (231--391) versus 144 (101--197). The breakfast does not interfer with the result of the TEC. In asthmatic subjects, a significant inverse correlation appears (r = 0,57, p less than 0,01) between the logarithm of TEC and the quotient: formula; see text. This correlation persists whatever may be the subject's age, the duration of the asthma or age at which he first contracted the illness. Asthma appeared after 40 years in 4 of the subjects: their TEC was higher (p less than 0,01) than in subjects who had become asthmatic before the age of forty. The respiratory function was lowered more in these 4 patients than in others who had been ill for the same time (p less than 0,001). The TEC is not related to results of skin testine with usuel inhalant allergens (grass pollen, house dust, cat's or dog's dander) or by result of a provocation test (by inhalation of allergen). Eosinophilia and bronchial obstruction are connected by one (or more) factors that may be inhalant allergens in extrinsec asthma and circulating immune complexes in intrinsec asthma."}
{"id": "PMID:219533", "title": "[Distribution and correlations of serum uric-acid in two French adult populations: 13,885 men and 6,861 women (author's transl)].", "content": "Distributions and correlations of serum uric acid (SUA) were studied in 13,885 men and 6,861 women who were between the ages of 20 and 90. In men and women the distribution of SUA is unimodal. The average SUA value is 6,28 mg/100 ml SD: 1,19) in men and 5,05 mg/100 ml (SD: 1,10) in women, 27% of the men and 4% of the women have a SUA level above 7 mg/100 ml. In men and in women correlations of SUA with an obesity index is strong (r = 0,272; r = 0,311). In men partial correlations between SUA and age, blood pressure, cholesterolemia, glycemia and hemoglobinemia diminish when obesity index is fixed. In women these correlations are stronger and do not vary when obesity index is fixed. In men and women the correlation between SUA and creatininemia is strong and do not vary when obesity index is fixed.", "contents": "[Distribution and correlations of serum uric-acid in two French adult populations: 13,885 men and 6,861 women (author's transl)]. Distributions and correlations of serum uric acid (SUA) were studied in 13,885 men and 6,861 women who were between the ages of 20 and 90. In men and women the distribution of SUA is unimodal. The average SUA value is 6,28 mg/100 ml SD: 1,19) in men and 5,05 mg/100 ml (SD: 1,10) in women, 27% of the men and 4% of the women have a SUA level above 7 mg/100 ml. In men and in women correlations of SUA with an obesity index is strong (r = 0,272; r = 0,311). In men partial correlations between SUA and age, blood pressure, cholesterolemia, glycemia and hemoglobinemia diminish when obesity index is fixed. In women these correlations are stronger and do not vary when obesity index is fixed. In men and women the correlation between SUA and creatininemia is strong and do not vary when obesity index is fixed."}
{"id": "PMID:219534", "title": "[Clinical and biological alarm signs of drug allergy (author's transl)].", "content": "Allergic symptoms to medications, which cause treatment to be interrupted in order to prevent more serious accidents such as anaphylactic shock, are reviewed and their practical importance discussed. They are of small significance if functional as they can be produced by placebos, but are more disturbing if cutaneous and due to various non-specific and sometimes vague immuno-allergic mechanisms. Isolated fever of the allergic type has to be interpreted within the framework of the affection being treated. Raised blood eosinophil levels are a valid sign of an allergic antibody-type reaction. The value of detailed observation of symptoms and signs in such cases is demonstrated.", "contents": "[Clinical and biological alarm signs of drug allergy (author's transl)]. Allergic symptoms to medications, which cause treatment to be interrupted in order to prevent more serious accidents such as anaphylactic shock, are reviewed and their practical importance discussed. They are of small significance if functional as they can be produced by placebos, but are more disturbing if cutaneous and due to various non-specific and sometimes vague immuno-allergic mechanisms. Isolated fever of the allergic type has to be interpreted within the framework of the affection being treated. Raised blood eosinophil levels are a valid sign of an allergic antibody-type reaction. The value of detailed observation of symptoms and signs in such cases is demonstrated."}
{"id": "PMID:219535", "title": "[Oral cholecystography: is the fatty meal compulsory (author's transl)].", "content": "An investigation on 1000 cases of oral cholecystography allowed us to collect 640 non pathologic opacifications of the gallblader and among them only 3 cases of pathological common bile ducts (0,47 percent). Consequently when the gallbladder appears normal on the oral cholecystography, the fatty meal seems to be non compulsory but only when clinical findings are in favor of a pancreatic disease or if there are pancreatic calcifications or if surgery has been performed anteriorly on the bile ducts, the liver or the pancreas.", "contents": "[Oral cholecystography: is the fatty meal compulsory (author's transl)]. An investigation on 1000 cases of oral cholecystography allowed us to collect 640 non pathologic opacifications of the gallblader and among them only 3 cases of pathological common bile ducts (0,47 percent). Consequently when the gallbladder appears normal on the oral cholecystography, the fatty meal seems to be non compulsory but only when clinical findings are in favor of a pancreatic disease or if there are pancreatic calcifications or if surgery has been performed anteriorly on the bile ducts, the liver or the pancreas."}
{"id": "PMID:219536", "title": "[Study of an homogeneous population of obese people and of its regression of weight under hypocaloric diet in hospital. I.--Characteristics of the population (author's transl)].", "content": "The study of a population of 79 obese people (62 women and 17 men) allowed to find out, and to specify a certain number of data shown through questionning, clinical examination and biological observations: the predominance of female application for weight regression treatments; the much more important number of major overweight with men; the idea of a \"certain\" age after which the micrease in weight is less important; the relation between the weigth after birth and overweight; the relation between how long you been futting on weight and the importance of your overweight; the frequency of overweight among your relatives. As for as spontaneous nutrition is concerned the frequency of normal food intake or even of hypocaloric intake, the immoderate proportion of fat intake and the frequency of the few, daily meals. As far as the biological aspect is concerned, the frequency of chemical diabetes and the possibility to distinguish from the oral glucose tolerance test together with the proportion of insulinemy, four groups of subjects ranging from the state of normal sugar regulation to proved diabetes, the frequency of hyperlipemy and hypercholesterolemy; the little difference between the free fat acids in the plasma, or an empty stomach as well as during the oral glucose tolerance test, with regard to normal subjects, with nevertheless, an important relation between the importance of the overweight and the average of fat acids.", "contents": "[Study of an homogeneous population of obese people and of its regression of weight under hypocaloric diet in hospital. I.--Characteristics of the population (author's transl)]. The study of a population of 79 obese people (62 women and 17 men) allowed to find out, and to specify a certain number of data shown through questionning, clinical examination and biological observations: the predominance of female application for weight regression treatments; the much more important number of major overweight with men; the idea of a \"certain\" age after which the micrease in weight is less important; the relation between the weigth after birth and overweight; the relation between how long you been futting on weight and the importance of your overweight; the frequency of overweight among your relatives. As for as spontaneous nutrition is concerned the frequency of normal food intake or even of hypocaloric intake, the immoderate proportion of fat intake and the frequency of the few, daily meals. As far as the biological aspect is concerned, the frequency of chemical diabetes and the possibility to distinguish from the oral glucose tolerance test together with the proportion of insulinemy, four groups of subjects ranging from the state of normal sugar regulation to proved diabetes, the frequency of hyperlipemy and hypercholesterolemy; the little difference between the free fat acids in the plasma, or an empty stomach as well as during the oral glucose tolerance test, with regard to normal subjects, with nevertheless, an important relation between the importance of the overweight and the average of fat acids."}
{"id": "PMID:219537", "title": "[Therapeutical approach to involuntary movements (author's transl)].", "content": "Thirty-three patients presenting an extra-pyramidal pathology with important involuntary movements have been treated with tiapride. The main beneficial results have been obtained in Huntington's chorea and in certain types of myoclony. The association with L-dopa, must be discussed. Only some L-dopa induced dyskinesias are improved; moreover tiaprid may antagonize L-dopa. The essential familial tremor is never improved.", "contents": "[Therapeutical approach to involuntary movements (author's transl)]. Thirty-three patients presenting an extra-pyramidal pathology with important involuntary movements have been treated with tiapride. The main beneficial results have been obtained in Huntington's chorea and in certain types of myoclony. The association with L-dopa, must be discussed. Only some L-dopa induced dyskinesias are improved; moreover tiaprid may antagonize L-dopa. The essential familial tremor is never improved."}
{"id": "PMID:219538", "title": "[Gastroparesis diabeticorum and bezoar (author's transl)].", "content": "Gastroparesis diabeticorum has been isolated by Kassander in 1958. Since that time, 65 well documented cases have been published. Very often the patients are asymptomatic and the disorder is discovered by an occasional X-ray examination of the G-I tract. But, sometimes, the diabetes of these patients becomes brittle and they loose weight; bezoar, gastroplegia and hemorrhages may occur. We report two additional cases with severe undernutrition and bezoar. The gastroparesis may be related to a vagal neuropathie. The treatment is disappointing; metoclopramide gives the best improvement.", "contents": "[Gastroparesis diabeticorum and bezoar (author's transl)]. Gastroparesis diabeticorum has been isolated by Kassander in 1958. Since that time, 65 well documented cases have been published. Very often the patients are asymptomatic and the disorder is discovered by an occasional X-ray examination of the G-I tract. But, sometimes, the diabetes of these patients becomes brittle and they loose weight; bezoar, gastroplegia and hemorrhages may occur. We report two additional cases with severe undernutrition and bezoar. The gastroparesis may be related to a vagal neuropathie. The treatment is disappointing; metoclopramide gives the best improvement."}
{"id": "PMID:219539", "title": "[Multicentric clinical trial of a new combination of a broad spectrum antimycotic and a dermocorticoid (author's transl)].", "content": "After having reviewed the conditions of use of an antimycotic-corticoid combination, the authors are reporting their clinical results on 183 patients of a new drug combining econazole and triamcinolon. This clinical trial demonstrates that the own activity of each component of the combination is entirely maintained, and that the new combination shows an original interest in the treatment of all inflammatory dermatomycoses, as well as inflammatory supra-infected dermatoses.", "contents": "[Multicentric clinical trial of a new combination of a broad spectrum antimycotic and a dermocorticoid (author's transl)]. After having reviewed the conditions of use of an antimycotic-corticoid combination, the authors are reporting their clinical results on 183 patients of a new drug combining econazole and triamcinolon. This clinical trial demonstrates that the own activity of each component of the combination is entirely maintained, and that the new combination shows an original interest in the treatment of all inflammatory dermatomycoses, as well as inflammatory supra-infected dermatoses."}
{"id": "PMID:219540", "title": "[Pathophysiology of chronic, bronchial hypersecretion (author's transl)].", "content": "The biochemical and rheological analysis of sputum allows one to detect abnormalities of the bronchial secretion and to describe the development of the bronchial disease. The main biochemical components of sputum and their biological activities are first described. The fibrillar structure of the mucus is related to heavy weight glycoproteins and these macromolecules contribute to the viscoelastic properties of the bronchial secretion, by their capacity to combine with other proteins such as secretory immunoglobulin A (S-IgA). As the chronic bronchial hypersecretory state progresses, the glandular synthesis of mucins and/or secretory proteins decreases while the passive filtration of blood-derived proteins, such as serumalbumin, increases. Such biochemical changes are frequently associated with a rise in viscosity and a loss in elasticity of sputum. These rheological modifications result in an impairment of the mucociliary clearance and therefore contribute to airway obstruction. The assessment of different indices such as the equilibrium in mucin secretion, S-IgA/serum-albumin ratio, viscosity and elasticity of sputum and its mucociliary transport rate, should lead to a better knowledge of the defense properties of the bronchial mucosa.", "contents": "[Pathophysiology of chronic, bronchial hypersecretion (author's transl)]. The biochemical and rheological analysis of sputum allows one to detect abnormalities of the bronchial secretion and to describe the development of the bronchial disease. The main biochemical components of sputum and their biological activities are first described. The fibrillar structure of the mucus is related to heavy weight glycoproteins and these macromolecules contribute to the viscoelastic properties of the bronchial secretion, by their capacity to combine with other proteins such as secretory immunoglobulin A (S-IgA). As the chronic bronchial hypersecretory state progresses, the glandular synthesis of mucins and/or secretory proteins decreases while the passive filtration of blood-derived proteins, such as serumalbumin, increases. Such biochemical changes are frequently associated with a rise in viscosity and a loss in elasticity of sputum. These rheological modifications result in an impairment of the mucociliary clearance and therefore contribute to airway obstruction. The assessment of different indices such as the equilibrium in mucin secretion, S-IgA/serum-albumin ratio, viscosity and elasticity of sputum and its mucociliary transport rate, should lead to a better knowledge of the defense properties of the bronchial mucosa."}
{"id": "PMID:219541", "title": "[Populational speciation or chromosomal speciation? About the book of Jean de Grouchy \"From the birth of species to the aberrations of life\" (author's transl)].", "content": "According to Jean de Grouchy, the emergence of a new species is dependent on an \"acceptable\" chromosomic rearrangement, which passing from the heterozygous state (in the original bearer) to the homozygous state (in some of his enbred offspring) becomes definitively established and creates a population sexually isolated from its acestors. He is thus using the idea of karyotype to develop the typological theory put forward at the beginning of the century which postulates that a single mutant is at the origin of a new species. Although he gives an important place to chromosomic rearrangements in the sexual isolation of a new species, J. Ruffi\u00e9 demonstrates by arguments taken from population genetics and from the immunological polymorphism of wild populations that speciation is almost always the result of the evolution of an entire group, which, because of geographic isolation, drift, and differential selection, diverges from the ancestral branch and finally becomes totally incapable of breeding with it. He proposes a model of speciation which includes the two processes population and cytologic. At a first step, the group is isolated geographically and continues its independent evolution; the second step consists of chromosomic recombinations which render the sexual isolation complete. The modifications of the karyotype make the process of speciation irreversible.", "contents": "[Populational speciation or chromosomal speciation? About the book of Jean de Grouchy \"From the birth of species to the aberrations of life\" (author's transl)]. According to Jean de Grouchy, the emergence of a new species is dependent on an \"acceptable\" chromosomic rearrangement, which passing from the heterozygous state (in the original bearer) to the homozygous state (in some of his enbred offspring) becomes definitively established and creates a population sexually isolated from its acestors. He is thus using the idea of karyotype to develop the typological theory put forward at the beginning of the century which postulates that a single mutant is at the origin of a new species. Although he gives an important place to chromosomic rearrangements in the sexual isolation of a new species, J. Ruffi\u00e9 demonstrates by arguments taken from population genetics and from the immunological polymorphism of wild populations that speciation is almost always the result of the evolution of an entire group, which, because of geographic isolation, drift, and differential selection, diverges from the ancestral branch and finally becomes totally incapable of breeding with it. He proposes a model of speciation which includes the two processes population and cytologic. At a first step, the group is isolated geographically and continues its independent evolution; the second step consists of chromosomic recombinations which render the sexual isolation complete. The modifications of the karyotype make the process of speciation irreversible."}
{"id": "PMID:219546", "title": "Detection of red and green flashes: evidence for cancellation and facilitation.", "content": "Green and red flashes of light will differentially stimulate the middle- and long-wavelength sensitive cones. Interaction of cone signals was studied by measuring increment thresholds for combinations of green and red flashes on a yellow adapting field. When the yellow adapting field was at 10.000 trolands (td), green and red incremental flashes (1 degree, 200-msec duration) produced cancellation when presented simultaneously and facilitation when presented sequentially. A green incremental flash (1.15 degrees, 200 msec, 5000-td adaptation field) and red decremental flash, or vice versa, produced facilitation when presented simultaneously. The results can be explained by color-differencing, opponent-mechanisms. The cancellation effect for the simultaneous incremental flashes largely disappeared when the flashes were exposed briefly (10 msec) or reduced in size (0.04 degrees). It is unlikely that the stimuli were exclusively detected by achromatic, luminance channels, as suggested by previous work, since observers could partially distinguish the hue of threshold flashes of 570- and 590-nm light (0.04 degrees, 10 msec) on a bright yellow field.", "contents": "Detection of red and green flashes: evidence for cancellation and facilitation. Green and red flashes of light will differentially stimulate the middle- and long-wavelength sensitive cones. Interaction of cone signals was studied by measuring increment thresholds for combinations of green and red flashes on a yellow adapting field. When the yellow adapting field was at 10.000 trolands (td), green and red incremental flashes (1 degree, 200-msec duration) produced cancellation when presented simultaneously and facilitation when presented sequentially. A green incremental flash (1.15 degrees, 200 msec, 5000-td adaptation field) and red decremental flash, or vice versa, produced facilitation when presented simultaneously. The results can be explained by color-differencing, opponent-mechanisms. The cancellation effect for the simultaneous incremental flashes largely disappeared when the flashes were exposed briefly (10 msec) or reduced in size (0.04 degrees). It is unlikely that the stimuli were exclusively detected by achromatic, luminance channels, as suggested by previous work, since observers could partially distinguish the hue of threshold flashes of 570- and 590-nm light (0.04 degrees, 10 msec) on a bright yellow field."}
{"id": "PMID:219542", "title": "[Iliac arteriopathy and Ehlers-Danlos disease (author's transl)].", "content": "A man of 40 years of age with the Ehlers-Danlos syndrome was noted to have an arteriopathy characterized by a rectilinear aspect of the iliac trunks with stenosis of the external iliac. Macroscopic examination showed thickening of the tunica of the arterial walls, while an increase in the elastic fibers in the intima was observed on histological examination. This type of arteriopathy appears to be extremely rare in the Ehlers-Danlos syndrome but these findings show similarities between this case and certain arterial affections of systematized elastorrhexis. The possible relationships between arteriopathy and elastic dysplasia are discussed as well as the classification of this very particular type of arteriopathy reported.", "contents": "[Iliac arteriopathy and Ehlers-Danlos disease (author's transl)]. A man of 40 years of age with the Ehlers-Danlos syndrome was noted to have an arteriopathy characterized by a rectilinear aspect of the iliac trunks with stenosis of the external iliac. Macroscopic examination showed thickening of the tunica of the arterial walls, while an increase in the elastic fibers in the intima was observed on histological examination. This type of arteriopathy appears to be extremely rare in the Ehlers-Danlos syndrome but these findings show similarities between this case and certain arterial affections of systematized elastorrhexis. The possible relationships between arteriopathy and elastic dysplasia are discussed as well as the classification of this very particular type of arteriopathy reported."}
{"id": "PMID:219547", "title": "Cushing's disease: megadose dexamethasone suppression in a case refractory to medical therapy.", "content": "A patient with Cushing's disease failed to show complete suppressibility of adrenal function with conventional \"high\" doses of dexamethasone (8 mg per day). Higher doses were required to achieve suppression. Pituitary irradiation and medical therapy (cyproheptadine, metyrapone, and aminoglutethimide) failed to control the disease, necessitating bilateral adrenalectomy. The diagnostic and therapeutic implications of megadose dexamethasone suppression have not been clearly addressed in the medical literature. It is possible that adrenal suppression achieved only with unconventionally high doses of steroids may be predictive of refractoriness to nonsurgical therapy.", "contents": "Cushing's disease: megadose dexamethasone suppression in a case refractory to medical therapy. A patient with Cushing's disease failed to show complete suppressibility of adrenal function with conventional \"high\" doses of dexamethasone (8 mg per day). Higher doses were required to achieve suppression. Pituitary irradiation and medical therapy (cyproheptadine, metyrapone, and aminoglutethimide) failed to control the disease, necessitating bilateral adrenalectomy. The diagnostic and therapeutic implications of megadose dexamethasone suppression have not been clearly addressed in the medical literature. It is possible that adrenal suppression achieved only with unconventionally high doses of steroids may be predictive of refractoriness to nonsurgical therapy."}
{"id": "PMID:219548", "title": "Identification of cytomegalovirus in bone marrow biopsy.", "content": "The bone marrow trephine biopsy has become a common procedure for evaluating hematopoietic abnormalities. Occasionally, the first clue to an infectious process is obtained from this source. A bone marrow biopsy, done to evaluate pancytopenia in a patient who had received a renal transplant, revealed large intranuclear inclusions diagnostic of cytomegalovirus. Antibody titers were initially negative but rose over the next few weeks to confirm the diagnosis. Even though the bone marrow biopsy may not be the best site for finding CMV inclusions, the careful examination of a random bone marrow biopsy, particularly in an immunosuppressed individual, may contribute to the diagnosis.", "contents": "Identification of cytomegalovirus in bone marrow biopsy. The bone marrow trephine biopsy has become a common procedure for evaluating hematopoietic abnormalities. Occasionally, the first clue to an infectious process is obtained from this source. A bone marrow biopsy, done to evaluate pancytopenia in a patient who had received a renal transplant, revealed large intranuclear inclusions diagnostic of cytomegalovirus. Antibody titers were initially negative but rose over the next few weeks to confirm the diagnosis. Even though the bone marrow biopsy may not be the best site for finding CMV inclusions, the careful examination of a random bone marrow biopsy, particularly in an immunosuppressed individual, may contribute to the diagnosis."}
{"id": "PMID:219543", "title": "[A case of sterility treated with sulpiride (author's transl)].", "content": "Oligospermia associated with asthenia is a frequent cause of sterility. Sulpiride, which is a regulator of autonomic nervous system function, was prescribed alone in such a case and pregnancy resulted on two occasions. The relationship between the normal duration of spermatogenesis and the periods during which sulpiride was prescribed was such that the hypothesis of a hormonal effect could be rejected and strongly suggests the existence of psychological factors in some patients with oligospermia.", "contents": "[A case of sterility treated with sulpiride (author's transl)]. Oligospermia associated with asthenia is a frequent cause of sterility. Sulpiride, which is a regulator of autonomic nervous system function, was prescribed alone in such a case and pregnancy resulted on two occasions. The relationship between the normal duration of spermatogenesis and the periods during which sulpiride was prescribed was such that the hypothesis of a hormonal effect could be rejected and strongly suggests the existence of psychological factors in some patients with oligospermia."}
{"id": "PMID:219544", "title": "[Isolated adenocarcinomatous transformation of uterine adenomyosis].", "content": "A case of epithelia malignant changes in uterine adenomyosis is reported. The adenocarcinomatous transformation in uterine adenomyosis is rare. It is necessary to identify exactly the lesion to detect several histological tests specially the integrity of endometrium. An initial phase by atypic hyperplasia and the eventual hormonal incidence are considered.", "contents": "[Isolated adenocarcinomatous transformation of uterine adenomyosis]. A case of epithelia malignant changes in uterine adenomyosis is reported. The adenocarcinomatous transformation in uterine adenomyosis is rare. It is necessary to identify exactly the lesion to detect several histological tests specially the integrity of endometrium. An initial phase by atypic hyperplasia and the eventual hormonal incidence are considered."}
{"id": "PMID:219545", "title": "[Tiapride in dermatology].", "content": "The action of tiapride was studied in various dermatological conditions with predominant psychosomatic features. A total of 36 cases were evaluated and results were satisfactory in 23 patients and poor in the other 13 cases. The indications which responded best were the lichens, eczemas, psoriatic affections and neurodermatoses. Tolerance was generally satisfactory.", "contents": "[Tiapride in dermatology]. The action of tiapride was studied in various dermatological conditions with predominant psychosomatic features. A total of 36 cases were evaluated and results were satisfactory in 23 patients and poor in the other 13 cases. The indications which responded best were the lichens, eczemas, psoriatic affections and neurodermatoses. Tolerance was generally satisfactory."}
{"id": "PMID:219550", "title": "Enterovirus survey before and after poliomyelitis vaccination in Kuala Lumpur, Malaysia.", "content": "Stool samples from healthy children mainly of the low income group aged 0 to 7 years of age from five Maternal and Child Health Centres in Kuala Lumpur were obtained for isolation of enteroviruses. The specimens were collected before and after the mass vaccination given in the face of polio type 1 epidemic which started in October, 1971. The prevelance rate of enteroviruses was 11.9% (3.0% polioviruses, 8.9% non-polio enteroviruses) before the vaccination and essentially the same after. Coxsackie A viruses predominated over the other enteroviruses in the pre- and post-vaccination phases. The highest isolation rate of enteroviruses was observed in children 0 to 2 years age. No significant differences in distribution by sex, race and month were noted. A sharp fall in the prevalence rates of total enteroviruses and polioviruses was noted shortly after the mass vaccination campaign However, the rates reverted to the pre-vaccination state during the next successive years.", "contents": "Enterovirus survey before and after poliomyelitis vaccination in Kuala Lumpur, Malaysia. Stool samples from healthy children mainly of the low income group aged 0 to 7 years of age from five Maternal and Child Health Centres in Kuala Lumpur were obtained for isolation of enteroviruses. The specimens were collected before and after the mass vaccination given in the face of polio type 1 epidemic which started in October, 1971. The prevelance rate of enteroviruses was 11.9% (3.0% polioviruses, 8.9% non-polio enteroviruses) before the vaccination and essentially the same after. Coxsackie A viruses predominated over the other enteroviruses in the pre- and post-vaccination phases. The highest isolation rate of enteroviruses was observed in children 0 to 2 years age. No significant differences in distribution by sex, race and month were noted. A sharp fall in the prevalence rates of total enteroviruses and polioviruses was noted shortly after the mass vaccination campaign However, the rates reverted to the pre-vaccination state during the next successive years."}
{"id": "PMID:219551", "title": "Respiratory viruses in hospital patients on the Witwatersrand. A 7-year study.", "content": "Virological investigations were carried out on 4 151 patients with respiratory disease hospitalized between May 1966 and April 1972. The groups examined were Black and White children and Black miners. Influenza viruses were more common among malnourished Black children and tended to cause more severe disease. This was also true of adenovirus and Herpesvirus hominis type 1 infections. Adenoviruses appear to be secondary invaders, frequently after a measles or influenza attack. A generalized epidemic of adenovirus type 7 occurred in 1967, the longest, coldest and most humid winter during the survey. The season of peak occurrence for respiratory syncytial (RS) virus is autumn, not winter as found elsewhere. The parainfluenza viruses differ from each other, types 1 and 2 being commoner in older children (12--48 months), mainly causing laryngotracheobronchitis (LTB), whereas type 3 is commoner in younger children (0--23 months), mainly causing pneumonia. The miners showed a preponderance of influenza A infections. The miners' origin from remote villages and high turnover rate create a situation where a given strain will persist at a moderate level for long periods, unlike in the general population where an outbreak lasts for only about 6--8 weeks. As opposed to other closed communities, adenovirus infections were rare. The reason for this is obscure.", "contents": "Respiratory viruses in hospital patients on the Witwatersrand. A 7-year study. Virological investigations were carried out on 4 151 patients with respiratory disease hospitalized between May 1966 and April 1972. The groups examined were Black and White children and Black miners. Influenza viruses were more common among malnourished Black children and tended to cause more severe disease. This was also true of adenovirus and Herpesvirus hominis type 1 infections. Adenoviruses appear to be secondary invaders, frequently after a measles or influenza attack. A generalized epidemic of adenovirus type 7 occurred in 1967, the longest, coldest and most humid winter during the survey. The season of peak occurrence for respiratory syncytial (RS) virus is autumn, not winter as found elsewhere. The parainfluenza viruses differ from each other, types 1 and 2 being commoner in older children (12--48 months), mainly causing laryngotracheobronchitis (LTB), whereas type 3 is commoner in younger children (0--23 months), mainly causing pneumonia. The miners showed a preponderance of influenza A infections. The miners' origin from remote villages and high turnover rate create a situation where a given strain will persist at a moderate level for long periods, unlike in the general population where an outbreak lasts for only about 6--8 weeks. As opposed to other closed communities, adenovirus infections were rare. The reason for this is obscure."}
{"id": "PMID:219552", "title": "Noncoordinate expression of SV40-induced transformation and tumorigenicity in mouse cell hybrids.", "content": "Somatic mouse cells hybrids formed by fusion of nontumorigenic 3T3 closely related SV40-transformed SVT2 cells were analyzed in a study designed to probe the genetic basis of the multiple phenotypic changes induced by SV40 transformation. These hybrids showed noncoordinate expression of the transformation phenotype. Although they cloned at high efficiency in medium with low serum and expressed the SV40 T-antigen of the SVT2 parent, hybrid cells grew poorly without anchorage and exhibited a cell and colony morphology intermediate between that of the parents. Tumorigenicity was assayed quantitatively by subcutaneous coinjection into athymic nude mice of serial dilutions of 10(2) to 10(5) hybrid cells with 10(7) lethally irradiated 3T3 cells. The results showed that 100--1000 times more hybrid cells had to be injected for tumor formation than were required with SVT2. These and other observations show that most 3T3/SVT2 hybrid cells are not tumorigenic but that each population contains a rare subset of tumorigenic cells.", "contents": "Noncoordinate expression of SV40-induced transformation and tumorigenicity in mouse cell hybrids. Somatic mouse cells hybrids formed by fusion of nontumorigenic 3T3 closely related SV40-transformed SVT2 cells were analyzed in a study designed to probe the genetic basis of the multiple phenotypic changes induced by SV40 transformation. These hybrids showed noncoordinate expression of the transformation phenotype. Although they cloned at high efficiency in medium with low serum and expressed the SV40 T-antigen of the SVT2 parent, hybrid cells grew poorly without anchorage and exhibited a cell and colony morphology intermediate between that of the parents. Tumorigenicity was assayed quantitatively by subcutaneous coinjection into athymic nude mice of serial dilutions of 10(2) to 10(5) hybrid cells with 10(7) lethally irradiated 3T3 cells. The results showed that 100--1000 times more hybrid cells had to be injected for tumor formation than were required with SVT2. These and other observations show that most 3T3/SVT2 hybrid cells are not tumorigenic but that each population contains a rare subset of tumorigenic cells."}
{"id": "PMID:219553", "title": "Cholesterol pool sizes and turnover following portacaval shunt in the dog.", "content": "Portacaval shunt has been shown to be effective in lowering the plasma cholesterol level of both man and experimental animal. However, the primary mechanism which effects this reduction is unclear. We have measured the rapidly, and the slowly, miscible cholesterol pool sizes and the cholesterol production rate in mongrel dogs, with the animals in the cholesterol steady state, using 14C-cholesterol plasma decay curve analysis. Five control animals and three one year postoperative portacaval shunt animals with a 50 per cent plasma cholesterol level reduction were studied. No differences were demonstrated in either the cholesterol pool sizes or the production rate. These data have led us to postulate two hypotheses to explain the mechanism of the hypocholesterolemic effect of the portacaval shunt.", "contents": "Cholesterol pool sizes and turnover following portacaval shunt in the dog. Portacaval shunt has been shown to be effective in lowering the plasma cholesterol level of both man and experimental animal. However, the primary mechanism which effects this reduction is unclear. We have measured the rapidly, and the slowly, miscible cholesterol pool sizes and the cholesterol production rate in mongrel dogs, with the animals in the cholesterol steady state, using 14C-cholesterol plasma decay curve analysis. Five control animals and three one year postoperative portacaval shunt animals with a 50 per cent plasma cholesterol level reduction were studied. No differences were demonstrated in either the cholesterol pool sizes or the production rate. These data have led us to postulate two hypotheses to explain the mechanism of the hypocholesterolemic effect of the portacaval shunt."}
{"id": "PMID:219555", "title": "Arteriovenous fistula and portal hypertension secondary to islet-cell tumor of the pancreas.", "content": "A case of portal hypertension secondary to an arteriovenous fistula in a pancreatic tumor is presented. Recurrent gastrointestinal hemorrhage prompted endoscopy which revealed esophageal varices and an abnormal papilla of Vater. Ultrasonography and arteriography were instrumental in demonstrating the nature of the pathological process. In this situation portal hypertension resulted from increased portal venous flow rather than portal obstruction. Correction must include obliteration of systemic arterial to portal venous communication.", "contents": "Arteriovenous fistula and portal hypertension secondary to islet-cell tumor of the pancreas. A case of portal hypertension secondary to an arteriovenous fistula in a pancreatic tumor is presented. Recurrent gastrointestinal hemorrhage prompted endoscopy which revealed esophageal varices and an abnormal papilla of Vater. Ultrasonography and arteriography were instrumental in demonstrating the nature of the pathological process. In this situation portal hypertension resulted from increased portal venous flow rather than portal obstruction. Correction must include obliteration of systemic arterial to portal venous communication."}
{"id": "PMID:219556", "title": "Epstein-Barr virus antibody responses and clinical illness in renal transplant recipients.", "content": "Among 88 renal transplant recipients evaluated for a change in Epstein-Barr virus (EBV) antibody status in the period after transplant, 22 showed a 4-fold rise and eight showed an 8-fold or greater rise in EBV antibody. Among the patients with an 8-fold or greater EBV ANTIBODY RISE, THE OCCURRENCE OF FEVER WAS FREQUENT, ONE PATIENT DEVELOPED A LYMPHOPROLIFERATIVE reaction, and one died with a malignant EBV infection. Patients without pretransplant antibody showed a longer mean time to antibody rise (104 +/- 23 days) than did those patients with pretransplant antibody (19 +/- 7 days). The longer incubation period in patients without pretransplant antibody was in the expected range for primary EBV infections. Both primary and secondary (reactivation) EBV infections occur in renal transplant patients. These infections may be assoicated with prolonged fever, and in unusual circumstances, may cause dramatic lymphoproliferative disease.", "contents": "Epstein-Barr virus antibody responses and clinical illness in renal transplant recipients. Among 88 renal transplant recipients evaluated for a change in Epstein-Barr virus (EBV) antibody status in the period after transplant, 22 showed a 4-fold rise and eight showed an 8-fold or greater rise in EBV antibody. Among the patients with an 8-fold or greater EBV ANTIBODY RISE, THE OCCURRENCE OF FEVER WAS FREQUENT, ONE PATIENT DEVELOPED A LYMPHOPROLIFERATIVE reaction, and one died with a malignant EBV infection. Patients without pretransplant antibody showed a longer mean time to antibody rise (104 +/- 23 days) than did those patients with pretransplant antibody (19 +/- 7 days). The longer incubation period in patients without pretransplant antibody was in the expected range for primary EBV infections. Both primary and secondary (reactivation) EBV infections occur in renal transplant patients. These infections may be assoicated with prolonged fever, and in unusual circumstances, may cause dramatic lymphoproliferative disease."}
{"id": "PMID:219557", "title": "Hepatoma with obstructive jaundice due to the migration of a tumor mass in the biliary tract: report of a successful resection.", "content": "A 51-year-old man underwent extended right lobectomy for hepatoma of the right lobe with obstructive jaundice due to migration of the tumor mass in the common and bilateral hepatic ducts. Severe jaundice amounting to 32.6 mg% and suppurative cholangitis were relieved by drainage through the cannulation into the hepatic ducts of the bilateral lobes. Although hepatoma was combined with liver cirrhosis, the patient could tolerate extended right lobectomy. The patient is doing relatively well without jaundice 2 years after operation, but a recurrent tumor appeared on the celiac angiogram taken 1 year and 6 months following operation. This is the fourth report on hepatic resection of such cases, and difficult problems involved with that procedure are presented and discussed.", "contents": "Hepatoma with obstructive jaundice due to the migration of a tumor mass in the biliary tract: report of a successful resection. A 51-year-old man underwent extended right lobectomy for hepatoma of the right lobe with obstructive jaundice due to migration of the tumor mass in the common and bilateral hepatic ducts. Severe jaundice amounting to 32.6 mg% and suppurative cholangitis were relieved by drainage through the cannulation into the hepatic ducts of the bilateral lobes. Although hepatoma was combined with liver cirrhosis, the patient could tolerate extended right lobectomy. The patient is doing relatively well without jaundice 2 years after operation, but a recurrent tumor appeared on the celiac angiogram taken 1 year and 6 months following operation. This is the fourth report on hepatic resection of such cases, and difficult problems involved with that procedure are presented and discussed."}
{"id": "PMID:219560", "title": "Prevalence of antibodies to equine viruses in the Netherlands.", "content": "The prevalence of antibodies to various viruses was investigated in a series of serum samples collected from horses in the Netherlands between 1963 and 1966 and from 1972 onwards. Neutralizing antibodies to equine rhinopneumonitis virus, equine arteritis virus and to equine rhinovirus types 1 and 2 were detected in respectively 76%, 14%, 66% and 59% of the equine serum samples tested. The observed incidence of serum samples positive to equine adenovirus in the complement fixation test was 39%. Precipitating antibodies to equine infectious anaemia virus were detected only in serum samples from two horses imported from abroad. Haemagglutination inhibiting antibodies to Myxovirus influenzae A/equi-1, M. Influenzae A/equi-2, and Reovirus types 1, 2, and 3 were present in respectively 82%, 50%, 10%, 33% and 3.6% of the serum samples tested. The most frequently observed incidence of antibodies to the various equine respiratory viruses occurred in the groups of horses having repeatedly contact with other horses.", "contents": "Prevalence of antibodies to equine viruses in the Netherlands. The prevalence of antibodies to various viruses was investigated in a series of serum samples collected from horses in the Netherlands between 1963 and 1966 and from 1972 onwards. Neutralizing antibodies to equine rhinopneumonitis virus, equine arteritis virus and to equine rhinovirus types 1 and 2 were detected in respectively 76%, 14%, 66% and 59% of the equine serum samples tested. The observed incidence of serum samples positive to equine adenovirus in the complement fixation test was 39%. Precipitating antibodies to equine infectious anaemia virus were detected only in serum samples from two horses imported from abroad. Haemagglutination inhibiting antibodies to Myxovirus influenzae A/equi-1, M. Influenzae A/equi-2, and Reovirus types 1, 2, and 3 were present in respectively 82%, 50%, 10%, 33% and 3.6% of the serum samples tested. The most frequently observed incidence of antibodies to the various equine respiratory viruses occurred in the groups of horses having repeatedly contact with other horses."}
{"id": "PMID:219561", "title": "Effect of polybrominated biphenyls on drug metabolizing enzymes in different tissues of C57 mice.", "content": "Polybrominated biphenyls (PBBs) are structurally very close to polychlorinated biphenyls (PCBs) which are known to be potent inducers of xenobiotic biotransformation reactions. We have studied the effects of 2 industrial PBB-mixtures, \"hexabromobiphenyl\" (HBB) and \"octabromobiphenyl\" (OBB), on enzymes catalyzing drug hydroxylation, epoxide hydration, and conjugation reactions in different tissues of C57 mice. The enzyme activities were measured 10 days after a single i.p. injection of PBBs (75 mg/kg). HBB enhanced the activities of hepatic AHH (1.9-fold), ethoxycoumarin deethylase (5.7-fold), epoxide hydratase (1.5-fold), glutathione S-transferase (1.7-fold) and UDP-glucuronosyltransferase (1.5-fold). In the kidney HBB enhanced the activity of UDP-blucuronosyltransferase 1.5-fold. OBB caused in increase in the activities of liver AHH (1.5-fold), ethoxycoumarin deethylase (2.4-fold) and glutathione S-transferase (1.4-fold). A slight increase was also seen in the activity of UDP-glucuronosyltransferase in digitoninactivated liver microsomes of OBB-treated mice. In the kidney OBB caused a slight but statistically significant decrease in glutathione S-transferase activity. Intraperitoneally injected bromobiphenyls had no effects on these drug metabolizing enzymes in the lung of C57 mice. These results were similar to the effects caused by a mixture of PCBs.", "contents": "Effect of polybrominated biphenyls on drug metabolizing enzymes in different tissues of C57 mice. Polybrominated biphenyls (PBBs) are structurally very close to polychlorinated biphenyls (PCBs) which are known to be potent inducers of xenobiotic biotransformation reactions. We have studied the effects of 2 industrial PBB-mixtures, \"hexabromobiphenyl\" (HBB) and \"octabromobiphenyl\" (OBB), on enzymes catalyzing drug hydroxylation, epoxide hydration, and conjugation reactions in different tissues of C57 mice. The enzyme activities were measured 10 days after a single i.p. injection of PBBs (75 mg/kg). HBB enhanced the activities of hepatic AHH (1.9-fold), ethoxycoumarin deethylase (5.7-fold), epoxide hydratase (1.5-fold), glutathione S-transferase (1.7-fold) and UDP-glucuronosyltransferase (1.5-fold). In the kidney HBB enhanced the activity of UDP-blucuronosyltransferase 1.5-fold. OBB caused in increase in the activities of liver AHH (1.5-fold), ethoxycoumarin deethylase (2.4-fold) and glutathione S-transferase (1.4-fold). A slight increase was also seen in the activity of UDP-glucuronosyltransferase in digitoninactivated liver microsomes of OBB-treated mice. In the kidney OBB caused a slight but statistically significant decrease in glutathione S-transferase activity. Intraperitoneally injected bromobiphenyls had no effects on these drug metabolizing enzymes in the lung of C57 mice. These results were similar to the effects caused by a mixture of PCBs."}
{"id": "PMID:219562", "title": "Adenosine triphosphatase activity in few tissues of a fresh water teleost, Channa gachua following in vivo exposure to endosulfan.", "content": "Fresh water teleost fish, Channa gachua, were chronically exposed to various sublethal concentrations of endosulfan (0.00534, 0.00355, 0.00213 and 0.00174 mg/1) at 25 +/- 4 degrees C for 30 and 60 days respectively. The study shows enzyme inhibitions, greatest in oligomycin-insensitive Mg2+ ATPase in brain, gill and liver tissues, with pronounced effects at highest endosulfan concentration for 60 days exposure. However, in kidney the highest inhibition was of oligomycin-sensitive (mitochondrial) Mg2+ ATPase. The study indicates that endosulfan interferes with energy metabolism in vivo. The marked sensitivity of mitochondrial Mg2+ ATPase to endosulfan is suggestive of the potential for endosulfan to interfere markedly with various energy requiring processes in the fish body.", "contents": "Adenosine triphosphatase activity in few tissues of a fresh water teleost, Channa gachua following in vivo exposure to endosulfan. Fresh water teleost fish, Channa gachua, were chronically exposed to various sublethal concentrations of endosulfan (0.00534, 0.00355, 0.00213 and 0.00174 mg/1) at 25 +/- 4 degrees C for 30 and 60 days respectively. The study shows enzyme inhibitions, greatest in oligomycin-insensitive Mg2+ ATPase in brain, gill and liver tissues, with pronounced effects at highest endosulfan concentration for 60 days exposure. However, in kidney the highest inhibition was of oligomycin-sensitive (mitochondrial) Mg2+ ATPase. The study indicates that endosulfan interferes with energy metabolism in vivo. The marked sensitivity of mitochondrial Mg2+ ATPase to endosulfan is suggestive of the potential for endosulfan to interfere markedly with various energy requiring processes in the fish body."}
{"id": "PMID:219566", "title": "Prolongation of islet allograft survival.", "content": "Pretreatment of donor rats with irradiation and silica followed by in vitro culture of the islets for 1 to 2 days prolonged survival of allografts across a minor histocompatibility barrier if \"hand-picked,\" clean islets were used for transplantation. Pretreatment of donor rats with irradiation and silica in conjunction with a single injection of antilymphocyte serum (ALS) into the recipient produced a prolongation of survival of hand-picked islets transplanted across a major histocompatibility barrier.", "contents": "Prolongation of islet allograft survival. Pretreatment of donor rats with irradiation and silica followed by in vitro culture of the islets for 1 to 2 days prolonged survival of allografts across a minor histocompatibility barrier if \"hand-picked,\" clean islets were used for transplantation. Pretreatment of donor rats with irradiation and silica in conjunction with a single injection of antilymphocyte serum (ALS) into the recipient produced a prolongation of survival of hand-picked islets transplanted across a major histocompatibility barrier."}
{"id": "PMID:219567", "title": "Encephalomyocarditis virus-induced diabetes mellitus treated by islet transplantation.", "content": "There is considerable evidence that at least some cases of juvenile onset diabetes mellitus in humans are a result of viral infection. Viral-induced diabetes in mice may provide an experimental counterpart more similar to the clinical situation than chemical-induced diabetes. Our experiments in such mice indicate that islet transplantation is effective in ameliorating viral-induced diabetes and is encouraging for ultimate clinical application of islet transplantation to juvenile onset insulin-dependent diabetics. In addition, our results show that islets in ectopic sites outside of the pancreas are resistant to damage induced by primary viral infection. The mechanism of this resistance is obscure and will be the subject of future investigations.", "contents": "Encephalomyocarditis virus-induced diabetes mellitus treated by islet transplantation. There is considerable evidence that at least some cases of juvenile onset diabetes mellitus in humans are a result of viral infection. Viral-induced diabetes in mice may provide an experimental counterpart more similar to the clinical situation than chemical-induced diabetes. Our experiments in such mice indicate that islet transplantation is effective in ameliorating viral-induced diabetes and is encouraging for ultimate clinical application of islet transplantation to juvenile onset insulin-dependent diabetics. In addition, our results show that islets in ectopic sites outside of the pancreas are resistant to damage induced by primary viral infection. The mechanism of this resistance is obscure and will be the subject of future investigations."}
{"id": "PMID:219563", "title": "Adenine compounds: cerebrovascular effects in vitro with reference to their possible involvement in migraine.", "content": "Adenosine and adenine compounds (AMP, cyclic AMP, ADP and ATP) markedly dilated feline and human pial arteries in vitro, the effect being more prominent with increasing tone of the vessel (active tonic contraction induced by prostaglandin F 2 alpha or serotonin). In contrast, the various adenine compounds were unable to produce any dilation of extracranial arteries tested (branches of lingual, external maxillary, and superficial temporal arteries). The degree of dilatation depended upon the perivascular potassium concentration, so that low potassium increased Emax and reduced ED50 values. Possible involvement of adenine compounds in the vasodilatory phase of the migraine attack is discussed.", "contents": "Adenine compounds: cerebrovascular effects in vitro with reference to their possible involvement in migraine. Adenosine and adenine compounds (AMP, cyclic AMP, ADP and ATP) markedly dilated feline and human pial arteries in vitro, the effect being more prominent with increasing tone of the vessel (active tonic contraction induced by prostaglandin F 2 alpha or serotonin). In contrast, the various adenine compounds were unable to produce any dilation of extracranial arteries tested (branches of lingual, external maxillary, and superficial temporal arteries). The degree of dilatation depended upon the perivascular potassium concentration, so that low potassium increased Emax and reduced ED50 values. Possible involvement of adenine compounds in the vasodilatory phase of the migraine attack is discussed."}
{"id": "PMID:219569", "title": "Agents affecting health of mother and child in a rural area of Kenya. XI. Antibodies against rotavirus in sera from children living in the Machakos District of Kenya.", "content": "207 sera from children under 5 years of age and living in the Machakos District in Kenya were tested in the Complement Fixation Test for antibodies against rotavirus. Two different antigens were used. The superiority of 'O' antigen over Nebraska calf diarrhoea virus antigen was confirmed. After a fall to 29 percent in the 6-8 months age group, the percentage of children with antibodies quickly rises with age to 80 percent at the age of 24 months and to practically 100 percent at the age of 30 months. This age-immunity curve suggests that the majority of children contract infections with rotavirus between 6 and 23 months of age. This is conform the pattern usually found in temperate climate countries.", "contents": "Agents affecting health of mother and child in a rural area of Kenya. XI. Antibodies against rotavirus in sera from children living in the Machakos District of Kenya. 207 sera from children under 5 years of age and living in the Machakos District in Kenya were tested in the Complement Fixation Test for antibodies against rotavirus. Two different antigens were used. The superiority of 'O' antigen over Nebraska calf diarrhoea virus antigen was confirmed. After a fall to 29 percent in the 6-8 months age group, the percentage of children with antibodies quickly rises with age to 80 percent at the age of 24 months and to practically 100 percent at the age of 30 months. This age-immunity curve suggests that the majority of children contract infections with rotavirus between 6 and 23 months of age. This is conform the pattern usually found in temperate climate countries."}
{"id": "PMID:219565", "title": "Occurrence of HBsAg, anti-HBs, the anti-CMV following the transfusion of blood products.", "content": "A retrospective study of the serum of 104 patients treated at Chelsea Naval Hospital between 1969 and 1972 was done. The donor blood products were not tested for the hepatitis B antigen before transfusion. The incidence of hepatitis B antigen following transfusion was about 2.8 per cent. The incidence of antibody to HBsAg prior to transfusion was 16 per cent, and about 27 per cent of the patients developed antibody to HBsAg following transfusion. The incidence of antibody to cytomegalovirus was about 22 per cent before transfusion, and 22 per cent of the patients developed complement fixing antibody against cytomegalovirus after transfusion. Since the patients received a variety of blood products it was not possible to determine retrsopectively which product, if any, produced the lowest incidence of hepatitis B antigen and transmission of cytomegalovirus.", "contents": "Occurrence of HBsAg, anti-HBs, the anti-CMV following the transfusion of blood products. A retrospective study of the serum of 104 patients treated at Chelsea Naval Hospital between 1969 and 1972 was done. The donor blood products were not tested for the hepatitis B antigen before transfusion. The incidence of hepatitis B antigen following transfusion was about 2.8 per cent. The incidence of antibody to HBsAg prior to transfusion was 16 per cent, and about 27 per cent of the patients developed antibody to HBsAg following transfusion. The incidence of antibody to cytomegalovirus was about 22 per cent before transfusion, and 22 per cent of the patients developed complement fixing antibody against cytomegalovirus after transfusion. Since the patients received a variety of blood products it was not possible to determine retrsopectively which product, if any, produced the lowest incidence of hepatitis B antigen and transmission of cytomegalovirus."}
{"id": "PMID:219570", "title": "[Effect of biologically active agents on the feeding response of Dileptus anser].", "content": "A study was made of the effects of pharmacological agents--adrenaline, noradrenaline, serotonine, dibenamine, theophylline, and emidazole--on the phagocytar activity of Dileptus anser. These effects were estimated in terms of food response changes towards chemical food models (CFM) made in cysteine, lecithine or tween-40 solutions. The above pharmacological agents were also tested as phagocytosis inductors. Of these, only adrenalin appeared to be an effective inductor of the food response. The CFM, made in adrenaline, was stimulated by 10(-6) M theophylline, and inhibited with 10(-4)--10(-8) M imidazole. The addition of 10(-3)--10(-12) M adrenaline or 10(-8)--10(-10) M serotonine to the Dileptus-containing medium stimulated phagocytosis of CFM. 5.10(-6) M dibenamin decreased phagocytotic intensity of CFM. 10(-6) M theophylline stimulated, while 10(-4) M inhibited the food response. It is proposed that protozoans have receptors capable of accepting hormones. A possible role of the system of cyclic AMP in transporting hormonal and food stimules in protozoans is discussed.", "contents": "[Effect of biologically active agents on the feeding response of Dileptus anser]. A study was made of the effects of pharmacological agents--adrenaline, noradrenaline, serotonine, dibenamine, theophylline, and emidazole--on the phagocytar activity of Dileptus anser. These effects were estimated in terms of food response changes towards chemical food models (CFM) made in cysteine, lecithine or tween-40 solutions. The above pharmacological agents were also tested as phagocytosis inductors. Of these, only adrenalin appeared to be an effective inductor of the food response. The CFM, made in adrenaline, was stimulated by 10(-6) M theophylline, and inhibited with 10(-4)--10(-8) M imidazole. The addition of 10(-3)--10(-12) M adrenaline or 10(-8)--10(-10) M serotonine to the Dileptus-containing medium stimulated phagocytosis of CFM. 5.10(-6) M dibenamin decreased phagocytotic intensity of CFM. 10(-6) M theophylline stimulated, while 10(-4) M inhibited the food response. It is proposed that protozoans have receptors capable of accepting hormones. A possible role of the system of cyclic AMP in transporting hormonal and food stimules in protozoans is discussed."}
{"id": "PMID:219571", "title": "[Role of phospholipids in the realization of catecholamine action].", "content": "The involvement of phospholipids into the function of the hormonoreactive system realizing the catecholamine action on the skeletal muscle metabolism was studied at different stages of chicken ontogenetic development. The phospholipase \"D\" treatment of the chicken muscle homogenate removed the epinephrine activating effect on phosphorylase. Phosphatidylserine and phosphatidylinositol not only completely restore the epinephrine responsiveness of this system but also slightly intensify it. The cAMP and Ca2+ effects on muscle phosphorylase are also removed after the phospholipase \"D\" treatment. But they are not restored by phosphatidylserine and phosphatidylinositol. It is shown that these membrane phospholipids do not accelerate the origination of catecholamine reactivity of the above-mentioned hormonecompetent system in the process of embryonic development.", "contents": "[Role of phospholipids in the realization of catecholamine action]. The involvement of phospholipids into the function of the hormonoreactive system realizing the catecholamine action on the skeletal muscle metabolism was studied at different stages of chicken ontogenetic development. The phospholipase \"D\" treatment of the chicken muscle homogenate removed the epinephrine activating effect on phosphorylase. Phosphatidylserine and phosphatidylinositol not only completely restore the epinephrine responsiveness of this system but also slightly intensify it. The cAMP and Ca2+ effects on muscle phosphorylase are also removed after the phospholipase \"D\" treatment. But they are not restored by phosphatidylserine and phosphatidylinositol. It is shown that these membrane phospholipids do not accelerate the origination of catecholamine reactivity of the above-mentioned hormonecompetent system in the process of embryonic development."}
{"id": "PMID:219572", "title": "[Lactate dehydrogenase isoenzyme in Rous sarcoma and muscle tissue of tumor-bearing hens].", "content": "The isoenzymic spectrum and lactate dehydrogenase activity (LDH) were studied in tumor and pectoral muscle of both chicken and adult hens on the 6th, 10th and 15th day after their infection with the Rous sarcoma virus. On the 14th day, unlike the muscles of intact hens, in the tumour the content of LDH-5 increases and that of rapidly migrating fraction LDG-1 and LDG-2 decreases. In pectoral muscles unaffected by the tumour (on the opposite side of the sternum) there is a tendency to an increase in LDH-4 content and to a decrease in LDH-1 and LDG-2 content, which is followed by a decreasing proportion of N/M subunits.", "contents": "[Lactate dehydrogenase isoenzyme in Rous sarcoma and muscle tissue of tumor-bearing hens]. The isoenzymic spectrum and lactate dehydrogenase activity (LDH) were studied in tumor and pectoral muscle of both chicken and adult hens on the 6th, 10th and 15th day after their infection with the Rous sarcoma virus. On the 14th day, unlike the muscles of intact hens, in the tumour the content of LDH-5 increases and that of rapidly migrating fraction LDG-1 and LDG-2 decreases. In pectoral muscles unaffected by the tumour (on the opposite side of the sternum) there is a tendency to an increase in LDH-4 content and to a decrease in LDH-1 and LDG-2 content, which is followed by a decreasing proportion of N/M subunits."}
{"id": "PMID:219577", "title": "[Nephroblastoma, partly appearing as a sarcoma botryoides of the renal pelvis (author's transl)].", "content": "A renal tumour in a 4-year old girl morphologically appeared as both a nephroblastoma and, in parts, as a sarcoma botryoides of the renal pelvis. The histogenesis of this dysontogenetic tumour is most probably due to a disturbance of growth and differentiation both of the metanephrogenic blastema as well as partly of the urethral bud. This type of dysontogenetic tumour is extremely rare. Problems of diagnosis and operative therapy and the possibility of postoperative radiation therapy and cystostatic treatment are discussed.", "contents": "[Nephroblastoma, partly appearing as a sarcoma botryoides of the renal pelvis (author's transl)]. A renal tumour in a 4-year old girl morphologically appeared as both a nephroblastoma and, in parts, as a sarcoma botryoides of the renal pelvis. The histogenesis of this dysontogenetic tumour is most probably due to a disturbance of growth and differentiation both of the metanephrogenic blastema as well as partly of the urethral bud. This type of dysontogenetic tumour is extremely rare. Problems of diagnosis and operative therapy and the possibility of postoperative radiation therapy and cystostatic treatment are discussed."}
{"id": "PMID:219573", "title": "[Succinate dehydrogenase and cytochrome oxidase activity in rat liver tissue under the influence of valexon].", "content": "The cytochrome oxidase and succinate dehydrogenase activities were studied in the liver supernatant fraction and homogenate of rats whom different amounts of valexon, organophosphoric pesticide with a hepatotoxic effect, were administered to. A significant increase in the enzymic activity in the supernatant fraction and the resulted rise in the value of the ratio of the activity in the supernatant fraction to that in the homogenate were found five days after a single administration of the preparation in a dose of 310 mg per 1 kg of body weight and after its three-month administration in a dose of 31 mg/kg. These changes may be believed to result from disturbances of the structural-functional state of the mitochondria due to penetration of valexon and its accumulation in them.", "contents": "[Succinate dehydrogenase and cytochrome oxidase activity in rat liver tissue under the influence of valexon]. The cytochrome oxidase and succinate dehydrogenase activities were studied in the liver supernatant fraction and homogenate of rats whom different amounts of valexon, organophosphoric pesticide with a hepatotoxic effect, were administered to. A significant increase in the enzymic activity in the supernatant fraction and the resulted rise in the value of the ratio of the activity in the supernatant fraction to that in the homogenate were found five days after a single administration of the preparation in a dose of 310 mg per 1 kg of body weight and after its three-month administration in a dose of 31 mg/kg. These changes may be believed to result from disturbances of the structural-functional state of the mitochondria due to penetration of valexon and its accumulation in them."}
{"id": "PMID:219578", "title": "Complication of Clorpactin WCS90 therapy for interstitial cystitis.", "content": "A case of ureteral fibrosis complicating Clorpactin WCS90 treatment for interstitial cystitis in a patient with vesicoureteral reflux is presented. The results of a laboratory experiment designed to study the effects of Clorpactin WCS90 on refluxing ureters are discussed.", "contents": "Complication of Clorpactin WCS90 therapy for interstitial cystitis. A case of ureteral fibrosis complicating Clorpactin WCS90 treatment for interstitial cystitis in a patient with vesicoureteral reflux is presented. The results of a laboratory experiment designed to study the effects of Clorpactin WCS90 on refluxing ureters are discussed."}
{"id": "PMID:219574", "title": "[Effect of a variable magnetic field on activity of enzymes of carbohydrate metabolism and tissue respiration in testicular tissue].", "content": "The 200 Oe magnetic field of power frequency produces an essential effect on metabolism in the tissue of the testicles which are highly sensitive to this factor. A single effect of the field for 24 h results in an increase in the glucose-6-phosphate dehydrogenase activity. 24-28 h after the cessation of the field action it lowers considerably as well as the cytochrome oxidase and hexokinase activities in mitochondria. The lactate dehydrogenase and succinate dehydrogenase activities increased in this case. Restoration of the initial level is marked on the 7th-14th days. Under repeated actions of the stimulation phase the enzymic activities under study (except the lactate dehydrogenase one) are decreased. The mentioned indices restore the initial level on the 14th-28th days. These changes correlates with dynamics of the testosterone level in the testicles and plasm.", "contents": "[Effect of a variable magnetic field on activity of enzymes of carbohydrate metabolism and tissue respiration in testicular tissue]. The 200 Oe magnetic field of power frequency produces an essential effect on metabolism in the tissue of the testicles which are highly sensitive to this factor. A single effect of the field for 24 h results in an increase in the glucose-6-phosphate dehydrogenase activity. 24-28 h after the cessation of the field action it lowers considerably as well as the cytochrome oxidase and hexokinase activities in mitochondria. The lactate dehydrogenase and succinate dehydrogenase activities increased in this case. Restoration of the initial level is marked on the 7th-14th days. Under repeated actions of the stimulation phase the enzymic activities under study (except the lactate dehydrogenase one) are decreased. The mentioned indices restore the initial level on the 14th-28th days. These changes correlates with dynamics of the testosterone level in the testicles and plasm."}
{"id": "PMID:219575", "title": "[Catalytic properties of solubilized brain Na+,K+-ATPase].", "content": "The results are presented of a kinetic study of solubilized Na+, K+-ATPase obtained by 0.2+ digitonin from the NaI treated microsome fraction of the bull brain. It is shown that in main kinetic parameters (KmATP, V, pH-optimum, optimal [Na+]/[K+] ratio, etc.) the solubilized Na+, K+-ATPase does not differ essentially from membrane-bound enzyme. These results evidence for the absence of changes in principle for the kinetic behaviour of Na+,K+-ATPase when solubilized with digitonin. Simultaneously there are certain differences for a temperature dependence (the bend position in the Arrhenius anamorphosis) of the solubilized enzyme and its sensitivity to the action of strophanthin K.", "contents": "[Catalytic properties of solubilized brain Na+,K+-ATPase]. The results are presented of a kinetic study of solubilized Na+, K+-ATPase obtained by 0.2+ digitonin from the NaI treated microsome fraction of the bull brain. It is shown that in main kinetic parameters (KmATP, V, pH-optimum, optimal [Na+]/[K+] ratio, etc.) the solubilized Na+, K+-ATPase does not differ essentially from membrane-bound enzyme. These results evidence for the absence of changes in principle for the kinetic behaviour of Na+,K+-ATPase when solubilized with digitonin. Simultaneously there are certain differences for a temperature dependence (the bend position in the Arrhenius anamorphosis) of the solubilized enzyme and its sensitivity to the action of strophanthin K."}
{"id": "PMID:219580", "title": "Pseudotumor of kidney.", "content": "Hypertrophy of the renal columns of Bertin may present as a mass, at times difficult to distinguish from neoplasia or cyst. Herein, we present a case characterized by the inability of this lesion to absorb 99mTc DTPA (99mTechnetium diethylenetriaminepentaacetic acid) isotope on two separate renal studies.", "contents": "Pseudotumor of kidney. Hypertrophy of the renal columns of Bertin may present as a mass, at times difficult to distinguish from neoplasia or cyst. Herein, we present a case characterized by the inability of this lesion to absorb 99mTc DTPA (99mTechnetium diethylenetriaminepentaacetic acid) isotope on two separate renal studies."}
{"id": "PMID:219582", "title": "Observations on outbreaks of respiratory disease in housed calves--(1) Epidemiological, clinical and microbiological findings.", "content": "In 47 of 50 outbreaks of respiratory disease in indoor calves which had never been to grass there was clinical evidence of pneumonia in all animals examined. Calf housing was in most cases considered unsatisfactory. Virus activity was detected in 70 per cent of outbreaks investigated within a few days post onset of respiratory signs. Parainfluenza (PI) 3 and respiratory syncitial virus (RSV) were the viruses most frequently involved. In the majority of outbreaks Mycoplasma species and Pasteurella multocida were present in the upper respiratory tract of affected calves.", "contents": "Observations on outbreaks of respiratory disease in housed calves--(1) Epidemiological, clinical and microbiological findings. In 47 of 50 outbreaks of respiratory disease in indoor calves which had never been to grass there was clinical evidence of pneumonia in all animals examined. Calf housing was in most cases considered unsatisfactory. Virus activity was detected in 70 per cent of outbreaks investigated within a few days post onset of respiratory signs. Parainfluenza (PI) 3 and respiratory syncitial virus (RSV) were the viruses most frequently involved. In the majority of outbreaks Mycoplasma species and Pasteurella multocida were present in the upper respiratory tract of affected calves."}
{"id": "PMID:219584", "title": "Observations on outbreaks of respiratory disease in calves associated with parainfluenza type 3 virus and respiratory syncytial virus infection.", "content": "In four outbreaks of indoor calf pneumonia, dyspnoea was a prominent clinical finding. At necropsy it was associated with pneumonia involving the cranial lobes of the lung and severe pulmonary emphysema. Histological examination of lung tissue revealed bronchiolitis and alveolitis with alveolar epithelial cell hyperplasia and multinucleate syncytium formation. Intraalveolar haemorrhage, intra-alveolar oedema and hyaline membrane formation were also noted. In all cases parainfluenza type 3 (PI3) virus was isolated from the lungs. In each of the four outbreaks there was evidence of PI3 virus and respiratory syncitial virus (RSV) infection.", "contents": "Observations on outbreaks of respiratory disease in calves associated with parainfluenza type 3 virus and respiratory syncytial virus infection. In four outbreaks of indoor calf pneumonia, dyspnoea was a prominent clinical finding. At necropsy it was associated with pneumonia involving the cranial lobes of the lung and severe pulmonary emphysema. Histological examination of lung tissue revealed bronchiolitis and alveolitis with alveolar epithelial cell hyperplasia and multinucleate syncytium formation. Intraalveolar haemorrhage, intra-alveolar oedema and hyaline membrane formation were also noted. In all cases parainfluenza type 3 (PI3) virus was isolated from the lungs. In each of the four outbreaks there was evidence of PI3 virus and respiratory syncitial virus (RSV) infection."}
{"id": "PMID:219586", "title": "[Experiments with the simultaneous or combined vaccination of chicks against Marek's disease and Newcastle disease].", "content": "Simultaneous vaccination was carried out of day-old chicks against Marek's disease (strain C3--1) and Newcastle disease (strains B1 and La Sota) which did not prove to be effective in conferring a lasting immunity to Newcastle disease though it was tolerated without any disturbances whatever. One could resort to it by way of an exception only, with an obligatory revaccination 15 days later, when the unfavourable epizootic status made it necessary. The immunity built up against Marek's disease did not seem to be affected by the simultaneous or succeeding vaccination against Newcastle disease with live lentogenic strains. Effective in conferring solid immunity against Newcastle disease proved the combined application of the two vaccines in the following order: treatment of day-old chicks with a vaccine against Marek's disease and vaccination of the same chicks at the age of 8 days with a vaccine against Newcastle disease (strain B1) at a half rate, employing the spray method, followed by revaccination 15 days later with the La Sota vaccine at a full rate, employing the aerosol method.", "contents": "[Experiments with the simultaneous or combined vaccination of chicks against Marek's disease and Newcastle disease]. Simultaneous vaccination was carried out of day-old chicks against Marek's disease (strain C3--1) and Newcastle disease (strains B1 and La Sota) which did not prove to be effective in conferring a lasting immunity to Newcastle disease though it was tolerated without any disturbances whatever. One could resort to it by way of an exception only, with an obligatory revaccination 15 days later, when the unfavourable epizootic status made it necessary. The immunity built up against Marek's disease did not seem to be affected by the simultaneous or succeeding vaccination against Newcastle disease with live lentogenic strains. Effective in conferring solid immunity against Newcastle disease proved the combined application of the two vaccines in the following order: treatment of day-old chicks with a vaccine against Marek's disease and vaccination of the same chicks at the age of 8 days with a vaccine against Newcastle disease (strain B1) at a half rate, employing the spray method, followed by revaccination 15 days later with the La Sota vaccine at a full rate, employing the aerosol method."}
{"id": "PMID:219587", "title": "[Radial immunodiffusion study of foot-and-mouth disease virus type A].", "content": "The radial immunodiffusion(RI), was used to study F. M. D. viruses, type A. It was found that the specific linkage between F. M. D. antigens and antibodies could be demonstrated through RI with the formation of precipitation circles. It was demonstrated that specific reactions were produced when homologus or heterologus antigens and sera of one and the same F. M. D. virus type interacted. The size of the precipitation circles proved inversely proportional to the concentration of antibodies in the homologous systems. It was also established that RI could be made use of in the demonstration of some subtype differences between the F. M. D. antigens of type A. Discussed is the problem of RI sensitivity as well as the possibility of using this technique for the early diagnosis of the F. M. D. infection and the study of the F. M. D. viruses.", "contents": "[Radial immunodiffusion study of foot-and-mouth disease virus type A]. The radial immunodiffusion(RI), was used to study F. M. D. viruses, type A. It was found that the specific linkage between F. M. D. antigens and antibodies could be demonstrated through RI with the formation of precipitation circles. It was demonstrated that specific reactions were produced when homologus or heterologus antigens and sera of one and the same F. M. D. virus type interacted. The size of the precipitation circles proved inversely proportional to the concentration of antibodies in the homologous systems. It was also established that RI could be made use of in the demonstration of some subtype differences between the F. M. D. antigens of type A. Discussed is the problem of RI sensitivity as well as the possibility of using this technique for the early diagnosis of the F. M. D. infection and the study of the F. M. D. viruses."}
{"id": "PMID:219591", "title": "Study of host antigens in the envelopes of different myxo- and paramyxoviruses cultivated in the embryonated hen egg.", "content": "By immunoelectrophoretic analysis it was shown that different viruses--such as myxo- (influenza A0PR8) and paramyxoviruses (Sendai, SV5, NDV, mumps)--cultivated in the same host cells (chorioallantoic membranes) incorporate similar host antigens into their envelopes. The amount of host cell antigens incorporated into the virus envelopes differs from one virus to another. The fact that incorporation of host cell antigens occurs only after a virus-induced modification seems to be a general characteristic of enveloped viruses such as myxo- and paramyxoviruses.", "contents": "Study of host antigens in the envelopes of different myxo- and paramyxoviruses cultivated in the embryonated hen egg. By immunoelectrophoretic analysis it was shown that different viruses--such as myxo- (influenza A0PR8) and paramyxoviruses (Sendai, SV5, NDV, mumps)--cultivated in the same host cells (chorioallantoic membranes) incorporate similar host antigens into their envelopes. The amount of host cell antigens incorporated into the virus envelopes differs from one virus to another. The fact that incorporation of host cell antigens occurs only after a virus-induced modification seems to be a general characteristic of enveloped viruses such as myxo- and paramyxoviruses."}
{"id": "PMID:219589", "title": "Serum antibodies to some oncogenic viruses in the child.", "content": "The presence of complement fixing antibodies to four viruses with oncogenic potential for animals was studied in children (including neonates and infants). Antibodies to herpes, adenovirus and avian \"gs\" sarcoma-leukosis antigens were detected, but there were no antibodies to SV-40. Positivity percentages varied with age and with the antigen used. Possible explanations of the appearance of these antibodies in the child are provided.", "contents": "Serum antibodies to some oncogenic viruses in the child. The presence of complement fixing antibodies to four viruses with oncogenic potential for animals was studied in children (including neonates and infants). Antibodies to herpes, adenovirus and avian \"gs\" sarcoma-leukosis antigens were detected, but there were no antibodies to SV-40. Positivity percentages varied with age and with the antigen used. Possible explanations of the appearance of these antibodies in the child are provided."}
{"id": "PMID:219592", "title": "Incidence of viral antibodies in patients with various forms of cancer.", "content": "The results of over 13,500 serological reactions performed in about 3,400 human sera collected from patients with various forms of cancer and from apparently healthy subjects have shown that the humoral immune reactivity of cancer patients as regards their viral antibody response is similar to that of apparently healthy subjects (blood donors or workers exposed to the risk of occupational contact with animal tumor viruses). The authors also remark the presence in the population of antibodies to some viruses with oncogenic potential proved so far only for mammals (adenovirus, SV-40, RSV) or to ubiquitous viruses (e.g. herpes virus) whose transforming activity has been demonstrated for several cell types in vitro and is suspected for some human tumors in vivo.", "contents": "Incidence of viral antibodies in patients with various forms of cancer. The results of over 13,500 serological reactions performed in about 3,400 human sera collected from patients with various forms of cancer and from apparently healthy subjects have shown that the humoral immune reactivity of cancer patients as regards their viral antibody response is similar to that of apparently healthy subjects (blood donors or workers exposed to the risk of occupational contact with animal tumor viruses). The authors also remark the presence in the population of antibodies to some viruses with oncogenic potential proved so far only for mammals (adenovirus, SV-40, RSV) or to ubiquitous viruses (e.g. herpes virus) whose transforming activity has been demonstrated for several cell types in vitro and is suspected for some human tumors in vivo."}
{"id": "PMID:219590", "title": "Immunofluorescence study of the presence of herpes type 1 and type 2 antigens in patients with cancer of the uterine cervix.", "content": "The presence of herpes simplex virus (HSV) antigens was tested by direct immunofluorescence in 24 cases of cervical carcinoma and in 1 case of uterine leiomyosarcoma, in comparison with 34 uterine fibroma preparations that served as controls. HSV antigens type 1 and type 2 were detected in 8 cervical carcinoma cases and in the patient with uterine leiomyosarcoma.", "contents": "Immunofluorescence study of the presence of herpes type 1 and type 2 antigens in patients with cancer of the uterine cervix. The presence of herpes simplex virus (HSV) antigens was tested by direct immunofluorescence in 24 cases of cervical carcinoma and in 1 case of uterine leiomyosarcoma, in comparison with 34 uterine fibroma preparations that served as controls. HSV antigens type 1 and type 2 were detected in 8 cervical carcinoma cases and in the patient with uterine leiomyosarcoma."}
{"id": "PMID:219611", "title": "[Comparative study of the effectiveness of the purification and concentration of herpes simplex virus types 1 and 2].", "content": "The results of comparative studies on concentration and purification of herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) by ficol density gradient centrifugation are presented. A two-phase distribution of extracellular HSV was established in phycol density gradient centrifugation: in zones with density of 1.110-1.114 and 1.088-1.085 g/ml. The effectiveness of purification of HSV preparations recovered from the corresponding gradient zones was determined by electron microscopy and quantitation of the contaminating cellular (radioactive) proteins in virus purification from a mixture of the culture fluid from infected cultures and the culture fluid from uninfected labeled human embryo skin-muscle tissue cultures (HESM) and a mixture of unlabeled extracellular HSV and a homogenate of labeled uninfected HESM cultures. In HSV purification from the virus-containing culture fluid the amount of cellular proteins was shown to decrease 500-fold in 150-fold virus concentration. In purification of extracellular HSV from the mixture with cell homogenate the amount of cellular proteins decreased 70- and 100-fold for HSV-2 and HSV-1, respectively. The infectious virus yield in phycol gradient centrifugation of a precipitate obtained by the addition of polyethylene glycol-6000 to the culture fluid for HSV-1 was 34.7% (in titrations in HESM cultures) and 38.4% (by intracerebral inoculation of mice weighing 5-6 g), and for HSV-2 20.2% and 26.3%, respectively.", "contents": "[Comparative study of the effectiveness of the purification and concentration of herpes simplex virus types 1 and 2]. The results of comparative studies on concentration and purification of herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) by ficol density gradient centrifugation are presented. A two-phase distribution of extracellular HSV was established in phycol density gradient centrifugation: in zones with density of 1.110-1.114 and 1.088-1.085 g/ml. The effectiveness of purification of HSV preparations recovered from the corresponding gradient zones was determined by electron microscopy and quantitation of the contaminating cellular (radioactive) proteins in virus purification from a mixture of the culture fluid from infected cultures and the culture fluid from uninfected labeled human embryo skin-muscle tissue cultures (HESM) and a mixture of unlabeled extracellular HSV and a homogenate of labeled uninfected HESM cultures. In HSV purification from the virus-containing culture fluid the amount of cellular proteins was shown to decrease 500-fold in 150-fold virus concentration. In purification of extracellular HSV from the mixture with cell homogenate the amount of cellular proteins decreased 70- and 100-fold for HSV-2 and HSV-1, respectively. The infectious virus yield in phycol gradient centrifugation of a precipitate obtained by the addition of polyethylene glycol-6000 to the culture fluid for HSV-1 was 34.7% (in titrations in HESM cultures) and 38.4% (by intracerebral inoculation of mice weighing 5-6 g), and for HSV-2 20.2% and 26.3%, respectively."}
{"id": "PMID:219610", "title": "[Further study of the leukocyte virus isolated in hepatitis A].", "content": "Two strains of leukocyte hepatitis virus (LHV) which had undergone 13 and 16 passages, respectively, in phytohemagglutinin-stimulated cultures of leukocytes from normal donors were studied in experiments with labelled precursors (3H-uridine and 14C-amino acids). The buoyant density of the virus (1,26 g/ml) and sedimentation constant of RNA (46 S) were determined. LHV was shown to be capable of reproduction in human kidney cell culture. The immunofluorescence test could be used with labeled convalescent sera for examinations of blood smears from patients for diagnosis of hepatitis A in foci of infection. In these tests, fluorescence was detected in the cytoplasm of lymphocytes and granulocytes but not in the nucleus. The immunofluorescence test with convalescent sera was successfully used for the examinations of smears of cultures of PHA-stimulated leukocytes of normal donors infected with LHV in order to prove the specificity of this virus in hepatitis A.", "contents": "[Further study of the leukocyte virus isolated in hepatitis A]. Two strains of leukocyte hepatitis virus (LHV) which had undergone 13 and 16 passages, respectively, in phytohemagglutinin-stimulated cultures of leukocytes from normal donors were studied in experiments with labelled precursors (3H-uridine and 14C-amino acids). The buoyant density of the virus (1,26 g/ml) and sedimentation constant of RNA (46 S) were determined. LHV was shown to be capable of reproduction in human kidney cell culture. The immunofluorescence test could be used with labeled convalescent sera for examinations of blood smears from patients for diagnosis of hepatitis A in foci of infection. In these tests, fluorescence was detected in the cytoplasm of lymphocytes and granulocytes but not in the nucleus. The immunofluorescence test with convalescent sera was successfully used for the examinations of smears of cultures of PHA-stimulated leukocytes of normal donors infected with LHV in order to prove the specificity of this virus in hepatitis A."}
{"id": "PMID:219612", "title": "[Adaptation of the type I poliomyelitis virus to cotton rats].", "content": "Adaptation of poliomyelitis virus type I (Mahoney strain) to the CNS of cotton rats which at the time of inoculation had been temporarily immunosuppressed with cyclophosphane is described. In the course of passages the virus properties were observed to change. The virus became pathogenic for cotton rats with normal immunologic responsiveness by the intracerebral, intraperitoneal and subcutaneous routes, as well as for white mice intracerebrally. Virions pathogenic for cotton rats were predominant in the adapted strain population.", "contents": "[Adaptation of the type I poliomyelitis virus to cotton rats]. Adaptation of poliomyelitis virus type I (Mahoney strain) to the CNS of cotton rats which at the time of inoculation had been temporarily immunosuppressed with cyclophosphane is described. In the course of passages the virus properties were observed to change. The virus became pathogenic for cotton rats with normal immunologic responsiveness by the intracerebral, intraperitoneal and subcutaneous routes, as well as for white mice intracerebrally. Virions pathogenic for cotton rats were predominant in the adapted strain population."}
{"id": "PMID:219615", "title": "[Experimental model of associated influenza-para-influenza infection].", "content": "An experimental model of associated influenza-parainfluenza infection has been developed. Simultaneous inoculation of mice with influenza A2/21/65 and parainfluenza type 3 or inoculation with these viruses at an interval of 24 hours was shown to produce a considerably more severe disease as manifested by the development of severe confluent pneumonias involving both lungs and death of the inoculated animals. The animals with the associated infection showed no significant difference in antibody titers or the intensity of immunity as compared with control groups (influenza or parainfluenza monoinfection). The development of the mixed infection was accompanied by the inhibition of neutrophilic and macrophage phagocytosis and inhibition of interferon production.", "contents": "[Experimental model of associated influenza-para-influenza infection]. An experimental model of associated influenza-parainfluenza infection has been developed. Simultaneous inoculation of mice with influenza A2/21/65 and parainfluenza type 3 or inoculation with these viruses at an interval of 24 hours was shown to produce a considerably more severe disease as manifested by the development of severe confluent pneumonias involving both lungs and death of the inoculated animals. The animals with the associated infection showed no significant difference in antibody titers or the intensity of immunity as compared with control groups (influenza or parainfluenza monoinfection). The development of the mixed infection was accompanied by the inhibition of neutrophilic and macrophage phagocytosis and inhibition of interferon production."}
{"id": "PMID:219616", "title": "[Change in the level of immunoglobulins A in the intestines of children after administration of live trivalent poliomyelitis vaccine by different methods].", "content": "It was shown that titers of the neutralizing activity of fecal extracts (coproantibody, CA) to poliomyelitis virus type II in the course of four administrations of live trivalent poliovaccine in drops directly into the mouth and in capsules were higher than CA titers to poliomyelitis virus types I and III. Particularly low CA titers to poliovirus types I and III were in children given the vaccine in the capsule, that is directly into the gastro-intestinal tract. Accordingly IgA levels in fecal extracts in this group of children were lower than in those given the vaccine in drops. In children of both groups no IgG of IgM (0.24 IU/ml) could be found in fecal extracts.", "contents": "[Change in the level of immunoglobulins A in the intestines of children after administration of live trivalent poliomyelitis vaccine by different methods]. It was shown that titers of the neutralizing activity of fecal extracts (coproantibody, CA) to poliomyelitis virus type II in the course of four administrations of live trivalent poliovaccine in drops directly into the mouth and in capsules were higher than CA titers to poliomyelitis virus types I and III. Particularly low CA titers to poliovirus types I and III were in children given the vaccine in the capsule, that is directly into the gastro-intestinal tract. Accordingly IgA levels in fecal extracts in this group of children were lower than in those given the vaccine in drops. In children of both groups no IgG of IgM (0.24 IU/ml) could be found in fecal extracts."}
{"id": "PMID:219617", "title": "[Cellular immunity reactions in herpetic eye infection].", "content": "The dynamics of leukocyte migration inhibition test (LMIT) and blast-transformation (BT) with herpes antigen were studied in 132 patients with ophthalmoherpes, 40 patients with obscure etiology of the eye disease and 40 normal donors. The specific response in LMTT was manifested by both inhibition and stimulation of leukocyte migration. Specific inhibition of leukocyte migration is detected mostly in exacerbations of the clinical process and may serve as a diagnostic sign of activation of herpetic infection in the patient. The specific blast-transformation in the group of patients with ophthalmoherpes was much higher by the rate and level if reaction than in control groups. The maximum level of BTT (up to 25%) was demonstrated in the favourable course of the disease; in severe processes the level was low (up to 2.7%) or the capacity of blast formation was lacking. The test may be prognostic in herpes infections of the eyes.", "contents": "[Cellular immunity reactions in herpetic eye infection]. The dynamics of leukocyte migration inhibition test (LMIT) and blast-transformation (BT) with herpes antigen were studied in 132 patients with ophthalmoherpes, 40 patients with obscure etiology of the eye disease and 40 normal donors. The specific response in LMTT was manifested by both inhibition and stimulation of leukocyte migration. Specific inhibition of leukocyte migration is detected mostly in exacerbations of the clinical process and may serve as a diagnostic sign of activation of herpetic infection in the patient. The specific blast-transformation in the group of patients with ophthalmoherpes was much higher by the rate and level if reaction than in control groups. The maximum level of BTT (up to 25%) was demonstrated in the favourable course of the disease; in severe processes the level was low (up to 2.7%) or the capacity of blast formation was lacking. The test may be prognostic in herpes infections of the eyes."}
{"id": "PMID:219618", "title": "[Herpes simplex in acute viral respiratory diseases].", "content": "Herpes in main viral acute respiratory diseases (ARD) in adults (influenza, parainfluenza, adenovirus and mixed infections) was studied by different laboratory methods of diagnosis. It was found that in 44.5% viral ARD were accompanied by herpes in the clinically overt or latent form. Herpes was detected with varying frequencies depending on the nosological forms of ARD as well as on the nature of the infection: more frequently in monoinfections than in mixed infections.", "contents": "[Herpes simplex in acute viral respiratory diseases]. Herpes in main viral acute respiratory diseases (ARD) in adults (influenza, parainfluenza, adenovirus and mixed infections) was studied by different laboratory methods of diagnosis. It was found that in 44.5% viral ARD were accompanied by herpes in the clinically overt or latent form. Herpes was detected with varying frequencies depending on the nosological forms of ARD as well as on the nature of the infection: more frequently in monoinfections than in mixed infections."}
{"id": "PMID:219620", "title": "[Method of determination of the number of enteroviruses present in natural waters].", "content": "The effectiveness of concentratin of enteroviruses present in water by adsorption on membrane filters, ion-exchange resin AB-17-8 and bentonite was compared with set concentrations of virus in water (0.05-0.1-0.5-2.5 and 12.5 PFU/ml). The effectiveness of concentration was shown to depend upon the initial dose of virus present in water. With virus adsorption on membrane filters and ionexchange resin the effectiveness of concentration was the higher (100 and 74%) the lower the virus dose in water (0.05 PFU/ml), with bentonite the effectiveness was the higher (60%) the higher virus dose in water (12.5 PFU/ml). A method is proposed for sufficiently accurate determination of virus concentration in water by simultaneous and parallel removal of virus particles in two ways one of which gives a maximum  effect with low doses of virus and the other with large doses.", "contents": "[Method of determination of the number of enteroviruses present in natural waters]. The effectiveness of concentratin of enteroviruses present in water by adsorption on membrane filters, ion-exchange resin AB-17-8 and bentonite was compared with set concentrations of virus in water (0.05-0.1-0.5-2.5 and 12.5 PFU/ml). The effectiveness of concentration was shown to depend upon the initial dose of virus present in water. With virus adsorption on membrane filters and ionexchange resin the effectiveness of concentration was the higher (100 and 74%) the lower the virus dose in water (0.05 PFU/ml), with bentonite the effectiveness was the higher (60%) the higher virus dose in water (12.5 PFU/ml). A method is proposed for sufficiently accurate determination of virus concentration in water by simultaneous and parallel removal of virus particles in two ways one of which gives a maximum  effect with low doses of virus and the other with large doses."}
{"id": "PMID:219625", "title": "[Experimental study of Coxsackie-streptococcal infection].", "content": "The pathological process due to Coxsackie A18 virus and hemolytic streptococcus infection was studied in adult white mice. Their synergistic effect was established as manifested by longer periods of virus detection in the blood and heart and the detection of the streptococcus in animals infected with an 8-fold lower dose. In cases of combined infection, signs of dystrophy, destruction and proliferation developed in the myocardium reaching the highest intensity when the virus and the microbe had been inoculated simultaneously.", "contents": "[Experimental study of Coxsackie-streptococcal infection]. The pathological process due to Coxsackie A18 virus and hemolytic streptococcus infection was studied in adult white mice. Their synergistic effect was established as manifested by longer periods of virus detection in the blood and heart and the detection of the streptococcus in animals infected with an 8-fold lower dose. In cases of combined infection, signs of dystrophy, destruction and proliferation developed in the myocardium reaching the highest intensity when the virus and the microbe had been inoculated simultaneously."}
{"id": "PMID:219629", "title": "[Corticotropic action of a new, synthetic analogue of ACTH (ACTH1-17) in man after intravenous, intramuscular and intranasal administration (author's transl)].", "content": "Ala1-lys17-ACTH(1-17)-4-amino-n-butylamide (ACTH1-17), a synthetic analogue of ACTH with shortened amino acid sequence exerts a corticotropic action of at least 8 hours duration in healthy male subjects after either intravenous or intramuscular administration. After intranasal administration of the compound an increased production of cortisol was observed only for three hours. The prolonged action of this new analogue of ACTH following intramuscular administration suggests that it may be of value for therapeutic purposes.", "contents": "[Corticotropic action of a new, synthetic analogue of ACTH (ACTH1-17) in man after intravenous, intramuscular and intranasal administration (author's transl)]. Ala1-lys17-ACTH(1-17)-4-amino-n-butylamide (ACTH1-17), a synthetic analogue of ACTH with shortened amino acid sequence exerts a corticotropic action of at least 8 hours duration in healthy male subjects after either intravenous or intramuscular administration. After intranasal administration of the compound an increased production of cortisol was observed only for three hours. The prolonged action of this new analogue of ACTH following intramuscular administration suggests that it may be of value for therapeutic purposes."}
{"id": "PMID:219623", "title": "[Virus-specific structures in Sendai virus infected Ehrlich ascitic carcinoma cells].", "content": "A virus-specific structure representing a ribonucleoprotein (RNP) associated with cell membranes was found in the cytoplasm of Sendai virus-infected cells of Ehrlich ascitic carcinoma. RNP could be separated from the membranes by recentrifugation of this structure in cesium chloride density gradient. In the liquid fraction, a structure with the same buoyant density possessing infectious activity was found. All structural polypeptides of virions with the exception of the membrane protein are found in the composition of the intracellular and extracellular structures.", "contents": "[Virus-specific structures in Sendai virus infected Ehrlich ascitic carcinoma cells]. A virus-specific structure representing a ribonucleoprotein (RNP) associated with cell membranes was found in the cytoplasm of Sendai virus-infected cells of Ehrlich ascitic carcinoma. RNP could be separated from the membranes by recentrifugation of this structure in cesium chloride density gradient. In the liquid fraction, a structure with the same buoyant density possessing infectious activity was found. All structural polypeptides of virions with the exception of the membrane protein are found in the composition of the intracellular and extracellular structures."}
{"id": "PMID:219630", "title": "[The incidence of antibodies to hepatitis A virus in people from Vienna and certain Austrian provinces (author's transl)].", "content": "The prevalence of antibodies to hepatitis A virus was measured by solid-phase radioimmunoassay in sera of 651 persons from Vienna, Lower Austria, Upper Austria, Carinthia and Burgenland. On subdivision of the subjects according to age groups, a curve resulted which showed a steep rise in persons between 20 and 40 years. In the age groups over 40 more than 80% of the test-persons possessed the specific antibody. In all age groups the population of Vienna showed a higher incidence of hepatitis A antibody than the people from rural areas.", "contents": "[The incidence of antibodies to hepatitis A virus in people from Vienna and certain Austrian provinces (author's transl)]. The prevalence of antibodies to hepatitis A virus was measured by solid-phase radioimmunoassay in sera of 651 persons from Vienna, Lower Austria, Upper Austria, Carinthia and Burgenland. On subdivision of the subjects according to age groups, a curve resulted which showed a steep rise in persons between 20 and 40 years. In the age groups over 40 more than 80% of the test-persons possessed the specific antibody. In all age groups the population of Vienna showed a higher incidence of hepatitis A antibody than the people from rural areas."}
{"id": "PMID:219626", "title": "[Effect of host cells on the course of chronic rabies virus infection in cell cultures].", "content": "Different patterns of rabies virus infection were observed in BHK-21/13S and HEp-2 cell cultures at late stages of persistent infections. The infection of BHK-21/13S cells was characterized by periodical increases and declines in the portion of the antigen-containing cells (from 100% to less than 1%) and low infectivity titers which did not correspond to fluctuations in the antigen production and occasional resistance to challenge with vesicular stomatitis virus. In contrast, persistently infected HEp-2 cell culture exhibited a more constant course of antigen production which never reached extreme points; the infectivity titers generally correlated with the portion of the antigen-containing cells. Cultivation in the presence of antirabies serum did not \"cure\" either of the cultures.", "contents": "[Effect of host cells on the course of chronic rabies virus infection in cell cultures]. Different patterns of rabies virus infection were observed in BHK-21/13S and HEp-2 cell cultures at late stages of persistent infections. The infection of BHK-21/13S cells was characterized by periodical increases and declines in the portion of the antigen-containing cells (from 100% to less than 1%) and low infectivity titers which did not correspond to fluctuations in the antigen production and occasional resistance to challenge with vesicular stomatitis virus. In contrast, persistently infected HEp-2 cell culture exhibited a more constant course of antigen production which never reached extreme points; the infectivity titers generally correlated with the portion of the antigen-containing cells. Cultivation in the presence of antirabies serum did not \"cure\" either of the cultures."}
{"id": "PMID:219633", "title": "A micromorphological and histoenzymological study on the third ventricular ependyma of the teleost Clarias batrachus (L.).", "content": "The circum ventricular region of C. batrachus is highly vascular and the ependymal cells appear differently when stained with haematoxylin, silver impregnation and Golgi-Cox techniques. The ventricule has PAS and AF positive material and some ependymal cells themselves are PAS positive. Few AF positive peptidergic and several AF negative small neurons have liquor contacting terminals. Golgi-Cox preparations reveal a variety of forms among the tanycytes. Their basal processes which are barbed or studded with varicosities, usually end on blood vessels and other neuronal elements. These basal processes themselves are often seen in direct morphological contact. Smaller silver positive cells without basal processes are also evident. Some tanycytes have apical processes resembling broadened endfeet. Few neurosecretory tracts are Golgi-Cox positive and can be differentiated from the tanycytic processes by their smooth surface. Varying degrees of ascorbic acid activity are noticed inside the ventricle, among the tanycytes and in the neurons of the NLT. Some of the latter neurons have liquor contacting terminals as well. The ChE activity noticed in some parts of the ependyma and in some NLT cells suggest their probable differential cholinergic control. Presence of SDH, NADPH and NADH diaphorases and cytochrome oxidase in varying quantities in the ependymal cells suggests that they are metabolically active. Presence of MAO positive tracts bridging the subependyma and ventricle suggests the degradation of monoamines at these sites. The presence of various enzymes and the morphological relationship of the tanycytes described in this species are comparable to those of the mammals. It is significant as this species is reported to have a median eminence morphologically resembling the tetrapods.", "contents": "A micromorphological and histoenzymological study on the third ventricular ependyma of the teleost Clarias batrachus (L.). The circum ventricular region of C. batrachus is highly vascular and the ependymal cells appear differently when stained with haematoxylin, silver impregnation and Golgi-Cox techniques. The ventricule has PAS and AF positive material and some ependymal cells themselves are PAS positive. Few AF positive peptidergic and several AF negative small neurons have liquor contacting terminals. Golgi-Cox preparations reveal a variety of forms among the tanycytes. Their basal processes which are barbed or studded with varicosities, usually end on blood vessels and other neuronal elements. These basal processes themselves are often seen in direct morphological contact. Smaller silver positive cells without basal processes are also evident. Some tanycytes have apical processes resembling broadened endfeet. Few neurosecretory tracts are Golgi-Cox positive and can be differentiated from the tanycytic processes by their smooth surface. Varying degrees of ascorbic acid activity are noticed inside the ventricle, among the tanycytes and in the neurons of the NLT. Some of the latter neurons have liquor contacting terminals as well. The ChE activity noticed in some parts of the ependyma and in some NLT cells suggest their probable differential cholinergic control. Presence of SDH, NADPH and NADH diaphorases and cytochrome oxidase in varying quantities in the ependymal cells suggests that they are metabolically active. Presence of MAO positive tracts bridging the subependyma and ventricle suggests the degradation of monoamines at these sites. The presence of various enzymes and the morphological relationship of the tanycytes described in this species are comparable to those of the mammals. It is significant as this species is reported to have a median eminence morphologically resembling the tetrapods."}
{"id": "PMID:219635", "title": "[\"Possessedness\" and exorcism in the year 1976 (author's transl)].", "content": "A 23 year-old woman died as a result of deficient food and liquid intake as well as of physical exhaustion brought about by an unchecked pathological displacement impulse. Finally pneumonia developed in a typical manner. During the previous 9 months exorcism had been carried out a total of 60 to 70 times, the last time being on the eve of her death, to \"expel demons\" and to heal the \"possessed\". Summarized the medical diagnosis of \"possession\" was: Parnoid-hallucinatory psychosis with epilepsy in the background of special psycho-social factors. During the time of influence by the priests who carried out the exorcism all medical treatment was denied. This, it was pointed out by the participants, occurred at the express wish of the \"possessed\" and also due to the conviction that medical aid would be ineffective. This fateful development took place in a milieu of belief in demons fostered by the priests and uncritical rejection of medico-scientific treatment methods. According to the results of the hearing of witnesses during the now legally valid proceedings ending with the exorcists and the deceased's parents being convicted for accidental homicide a doctor probably also participated in what happend in a reprehensible manner.", "contents": "[\"Possessedness\" and exorcism in the year 1976 (author's transl)]. A 23 year-old woman died as a result of deficient food and liquid intake as well as of physical exhaustion brought about by an unchecked pathological displacement impulse. Finally pneumonia developed in a typical manner. During the previous 9 months exorcism had been carried out a total of 60 to 70 times, the last time being on the eve of her death, to \"expel demons\" and to heal the \"possessed\". Summarized the medical diagnosis of \"possession\" was: Parnoid-hallucinatory psychosis with epilepsy in the background of special psycho-social factors. During the time of influence by the priests who carried out the exorcism all medical treatment was denied. This, it was pointed out by the participants, occurred at the express wish of the \"possessed\" and also due to the conviction that medical aid would be ineffective. This fateful development took place in a milieu of belief in demons fostered by the priests and uncritical rejection of medico-scientific treatment methods. According to the results of the hearing of witnesses during the now legally valid proceedings ending with the exorcists and the deceased's parents being convicted for accidental homicide a doctor probably also participated in what happend in a reprehensible manner."}
{"id": "PMID:219636", "title": "Effects of testosterone propionate and pituitary-adrenal hormones on the social behaviour of male ducklings (Anas platyrhynchos L.) in two test situations.", "content": "This experiment was designed to study in male ducklings the behavioural influence of testosterone propionate (= TP) injections, combined with pituitary-adrenal hormones administration, in two test situations: in groups of birds from the same residence cage or from visually isolated cages. It appears from the results that TP administration increased sexual but not aggressive behaviour, while pituitary-adrenal hormones induced very few effects. The responses of the birds were however modulated to a large extent by the type of test situation.", "contents": "Effects of testosterone propionate and pituitary-adrenal hormones on the social behaviour of male ducklings (Anas platyrhynchos L.) in two test situations. This experiment was designed to study in male ducklings the behavioural influence of testosterone propionate (= TP) injections, combined with pituitary-adrenal hormones administration, in two test situations: in groups of birds from the same residence cage or from visually isolated cages. It appears from the results that TP administration increased sexual but not aggressive behaviour, while pituitary-adrenal hormones induced very few effects. The responses of the birds were however modulated to a large extent by the type of test situation."}
{"id": "PMID:219637", "title": "[Qualitative and quantitative determinations of staphylokinase-activity (author's transl)].", "content": "Staphylokinase (SAK)-activated plasminogen reacted specifically with nitroanilide (N-benzoyl-DL-lysine-4-nitroanilide) to form intensively yellow 4-nitroaniline. This reaction did not occur with staphylococcal proteases. For qualitative SAK-determinations nitroanilide was incorporated in an agar medium. SAK diffused into the medium and caused a distinct change in color from white to yellow. For quantitative SAK-determination the conversion of colorless nitroanilide to yellow 4-nitroaniline was recorded photometrically at 405 nm. The optical density correlated well with SAK-activity of preparations with different degrees of purity (fig. 1, 2). Another quantitative procedure for SAK-activity could be conducted with fibrin in microtiter-plates (Fib-MTT). In this method, after 2-fold dilutions of SAK-preparations fibrinogen (stained blue with astrazonblue) and subsequently thrombin were added. SAK-activity was indicated by lysis of the blue-colored fibrin clots in the microtiter-plates (fig. 3). The Fib-MTT was particularly suitable for measuring wide ranges of SAK-activities.", "contents": "[Qualitative and quantitative determinations of staphylokinase-activity (author's transl)]. Staphylokinase (SAK)-activated plasminogen reacted specifically with nitroanilide (N-benzoyl-DL-lysine-4-nitroanilide) to form intensively yellow 4-nitroaniline. This reaction did not occur with staphylococcal proteases. For qualitative SAK-determinations nitroanilide was incorporated in an agar medium. SAK diffused into the medium and caused a distinct change in color from white to yellow. For quantitative SAK-determination the conversion of colorless nitroanilide to yellow 4-nitroaniline was recorded photometrically at 405 nm. The optical density correlated well with SAK-activity of preparations with different degrees of purity (fig. 1, 2). Another quantitative procedure for SAK-activity could be conducted with fibrin in microtiter-plates (Fib-MTT). In this method, after 2-fold dilutions of SAK-preparations fibrinogen (stained blue with astrazonblue) and subsequently thrombin were added. SAK-activity was indicated by lysis of the blue-colored fibrin clots in the microtiter-plates (fig. 3). The Fib-MTT was particularly suitable for measuring wide ranges of SAK-activities."}
{"id": "PMID:219638", "title": "Anticomplementarity in complement-fixation test with soluble antigens of the spotted fever group rickettsiae.", "content": "Anticomplementarity occurring in the complement-fixation (CF) test with soluble antigens of rickettsiae of the spotted fever (SF) group is caused by interaction of soluble antigens with guinea pig sera serving as the source of complement. The serum factor responsible for anticomplementarity is thermostable and cannot be removed by treatment of guinea pig serum with CO2 or nitrogen. An adverse effect of such serum was also observed upon its mixing with other guinea pig sera lacking anticomplementarity properties. An anticomplementarity factor present in the soluble rickettsial antigens was sensitive to treatment with potassium periodate.", "contents": "Anticomplementarity in complement-fixation test with soluble antigens of the spotted fever group rickettsiae. Anticomplementarity occurring in the complement-fixation (CF) test with soluble antigens of rickettsiae of the spotted fever (SF) group is caused by interaction of soluble antigens with guinea pig sera serving as the source of complement. The serum factor responsible for anticomplementarity is thermostable and cannot be removed by treatment of guinea pig serum with CO2 or nitrogen. An adverse effect of such serum was also observed upon its mixing with other guinea pig sera lacking anticomplementarity properties. An anticomplementarity factor present in the soluble rickettsial antigens was sensitive to treatment with potassium periodate."}
{"id": "PMID:219631", "title": "[Effect of age on the activity of Mg-Na-K-ATPase, as well as on the K and Na concentration in human erythrocytes].", "content": "42 persons of two age groups (14--28 years and 70--87 years) free of liver and hematological diseases without treatment with cardiac glycosides were investigated in this study. The activities of Mg++-ATPase and Na+-K+-ATPase were measured in red cell membranes. Furthermore the intracellular concentration of sodium and potassium was measured in erythrocytes of 10 persons. These results display a significant age dependent decrease of enzyme activities. Contrary to this, measurements of intracellular sodium and potassium concentrations disclosed no age dependent changes. There was no positive or negative correlation between the enzyme activities and the intracellular concentrations of sodium and potassium. The influence of 8 different drugs on Mg++-ATPase activities was proofed. The results displayed changes dependent on age and drug concentrations. The results were discussed with those of the literature.", "contents": "[Effect of age on the activity of Mg-Na-K-ATPase, as well as on the K and Na concentration in human erythrocytes]. 42 persons of two age groups (14--28 years and 70--87 years) free of liver and hematological diseases without treatment with cardiac glycosides were investigated in this study. The activities of Mg++-ATPase and Na+-K+-ATPase were measured in red cell membranes. Furthermore the intracellular concentration of sodium and potassium was measured in erythrocytes of 10 persons. These results display a significant age dependent decrease of enzyme activities. Contrary to this, measurements of intracellular sodium and potassium concentrations disclosed no age dependent changes. There was no positive or negative correlation between the enzyme activities and the intracellular concentrations of sodium and potassium. The influence of 8 different drugs on Mg++-ATPase activities was proofed. The results displayed changes dependent on age and drug concentrations. The results were discussed with those of the literature."}
{"id": "PMID:219632", "title": "Influence of age on thermotropic kinetics of enzymes involved in mitochondrial energy-metabolism.", "content": "Aging has recently been shown to promote lipid peroxidation of mitochondrial membranes by a mechanism involving chaotropic oxidants (5). The present paper reports on the relationship between these membrane alterations and the activities of lipid-dependent enzymes of isolated heart mitochondria from 3 month and 24 month old rats. 1. Temperature breaks of Arrhenius plots reveal age-dependent shifts to higher temperatures for the succinate oxidase system (delta t = 1,7 degrees C), the beta-hydroxybutyrate dehydrogenase, the succinate dehydrogenase and the ATP-ase (delta t = 3,0 degrees C). 2. Specific activities of the above enzymes are distinctly lowered in preparation from aged rats. 3. Thermotropic differences of the particular enzyme activities completely disappeared after solubilization of the lipid components by Triton X-100. 4. ESR studies exhibit a clear decrease in the fluidity of membrane lipids as a function of age. 5. Analysis of the membrane lipids by gas-liquid chromatography reveals a distinct age-dependent fall in the content of polyunsaturated fatty acids accompanied by a slow increase in the degree of fatty acid saturation. 6. It is concluded from the results that aging influences enzyme-protein-lipid interactions by radical-induced peroxidation of the surrounding membrane lipids, but does not affect the intrinsic properties of the membrane-bound enzymes themselves.", "contents": "Influence of age on thermotropic kinetics of enzymes involved in mitochondrial energy-metabolism. Aging has recently been shown to promote lipid peroxidation of mitochondrial membranes by a mechanism involving chaotropic oxidants (5). The present paper reports on the relationship between these membrane alterations and the activities of lipid-dependent enzymes of isolated heart mitochondria from 3 month and 24 month old rats. 1. Temperature breaks of Arrhenius plots reveal age-dependent shifts to higher temperatures for the succinate oxidase system (delta t = 1,7 degrees C), the beta-hydroxybutyrate dehydrogenase, the succinate dehydrogenase and the ATP-ase (delta t = 3,0 degrees C). 2. Specific activities of the above enzymes are distinctly lowered in preparation from aged rats. 3. Thermotropic differences of the particular enzyme activities completely disappeared after solubilization of the lipid components by Triton X-100. 4. ESR studies exhibit a clear decrease in the fluidity of membrane lipids as a function of age. 5. Analysis of the membrane lipids by gas-liquid chromatography reveals a distinct age-dependent fall in the content of polyunsaturated fatty acids accompanied by a slow increase in the degree of fatty acid saturation. 6. It is concluded from the results that aging influences enzyme-protein-lipid interactions by radical-induced peroxidation of the surrounding membrane lipids, but does not affect the intrinsic properties of the membrane-bound enzymes themselves."}
{"id": "PMID:219639", "title": "[Investigations on bloodcultures with three culture media containing Na-polyanetholsulfonate (aerobic iso- and hypertonic and anaerobic isotonic (author's transl)].", "content": "By using parallel culture techniques 330 blood specimens steming from patients of an intensive care unit were cultured simultanously in 3 media containing 0.05% Na-Poly-anetholsulfonate. Otherwise having an identical composition the media differed in the following respects : the isotonic medium A and the - by additional content of 10% sucrose - hypertonic medium B were used for aerobic culture. The anaerobic and isotonic medium C contained 2% Proteose-peptone, additionally. Without regards to the isolation of strictly anaerobic bacteria a total of 114 positive bloodcultures was obtained (tab. 1). The use of medium A resulted in 81 positive bloodcultures, that of medium B and C in 93 and 50, respectively (tab. 2). With the combined use of media A + B 103 positive bloodcultures would have been detected, with B + C 102, but with A + C 92 only (tab. 2). Of all 3 media the hypertonic medium B promotes bacterial growth most efficiently, but 13 strains grown in A did not grow in B (tab. 3), a fact that leads to the conclusion that isotonic as well as hypertonic aerobic media are employed in parallel advantageously. The effect of the hypertonic medium was expressed most distinctly with the isolation of grampositive bacteria (tab. 4). As during the period of this investigation the intensive care unit was afflicted by an outbreak of Serratia marcescens the predominance of this species among the other isolated microbes (tab. 5) is not surprising. While no difference of detection-time was observed between A and B, microbial growth in medium C seemed to be slower (fig). It was concluded that the use of 3 media, aerobic isotonic and hypertonic as well as anaerobic isotonic should be employed whenever possible.", "contents": "[Investigations on bloodcultures with three culture media containing Na-polyanetholsulfonate (aerobic iso- and hypertonic and anaerobic isotonic (author's transl)]. By using parallel culture techniques 330 blood specimens steming from patients of an intensive care unit were cultured simultanously in 3 media containing 0.05% Na-Poly-anetholsulfonate. Otherwise having an identical composition the media differed in the following respects : the isotonic medium A and the - by additional content of 10% sucrose - hypertonic medium B were used for aerobic culture. The anaerobic and isotonic medium C contained 2% Proteose-peptone, additionally. Without regards to the isolation of strictly anaerobic bacteria a total of 114 positive bloodcultures was obtained (tab. 1). The use of medium A resulted in 81 positive bloodcultures, that of medium B and C in 93 and 50, respectively (tab. 2). With the combined use of media A + B 103 positive bloodcultures would have been detected, with B + C 102, but with A + C 92 only (tab. 2). Of all 3 media the hypertonic medium B promotes bacterial growth most efficiently, but 13 strains grown in A did not grow in B (tab. 3), a fact that leads to the conclusion that isotonic as well as hypertonic aerobic media are employed in parallel advantageously. The effect of the hypertonic medium was expressed most distinctly with the isolation of grampositive bacteria (tab. 4). As during the period of this investigation the intensive care unit was afflicted by an outbreak of Serratia marcescens the predominance of this species among the other isolated microbes (tab. 5) is not surprising. While no difference of detection-time was observed between A and B, microbial growth in medium C seemed to be slower (fig). It was concluded that the use of 3 media, aerobic isotonic and hypertonic as well as anaerobic isotonic should be employed whenever possible."}
{"id": "PMID:219640", "title": "[The smallpox vaccination strain MVA: marker, genetic structure, experience gained with the parenteral vaccination and behavior in organisms with a debilitated defence mechanism (author's transl)].", "content": "The MVA virus is a lab virus ideally suited for vaccination of both man and animal which can be differentiated from the known Vaccinia strains by the use of numerous biological markers. Its reduced virulence for the chick embryo, for experimental animals and for man is a particularly characteristic feature. With the exception of chick embryo fibroblasts, the MVA virus grows in cell cultures only abortively. This applies particularly to cells of human origin in which the cytopathic effect and plaque formation are completely missing. The restriction analysis of the DNS of the MVA virus demonstrates that its genetic structure differs from that of the CVA basic virus and other orthopox viruses. In contrast to the WHO reference strain Elstree, the MVA virus has a genome shortened by about 9 per cent. The use of the MVA virus for human vaccination is particularly indicated in persons to be vaccinated for the first time and likely to entail a risk (on account of allergies etc.) because it brings about a state of revaccination without complications. The MVA virus can be administered in intracutaneous, subcutaneous or intramuscular injections. Innocuoursness and successful vaccination have been demonstrated in more than 120000 persons. While other Vaccinia strains, such as the Elstree virus, experience a drastic increase of virulence in the immunosuppressed organism (subjected to whole-body irradiation), the MVA virus cannot be activated not even in this situation.", "contents": "[The smallpox vaccination strain MVA: marker, genetic structure, experience gained with the parenteral vaccination and behavior in organisms with a debilitated defence mechanism (author's transl)]. The MVA virus is a lab virus ideally suited for vaccination of both man and animal which can be differentiated from the known Vaccinia strains by the use of numerous biological markers. Its reduced virulence for the chick embryo, for experimental animals and for man is a particularly characteristic feature. With the exception of chick embryo fibroblasts, the MVA virus grows in cell cultures only abortively. This applies particularly to cells of human origin in which the cytopathic effect and plaque formation are completely missing. The restriction analysis of the DNS of the MVA virus demonstrates that its genetic structure differs from that of the CVA basic virus and other orthopox viruses. In contrast to the WHO reference strain Elstree, the MVA virus has a genome shortened by about 9 per cent. The use of the MVA virus for human vaccination is particularly indicated in persons to be vaccinated for the first time and likely to entail a risk (on account of allergies etc.) because it brings about a state of revaccination without complications. The MVA virus can be administered in intracutaneous, subcutaneous or intramuscular injections. Innocuoursness and successful vaccination have been demonstrated in more than 120000 persons. While other Vaccinia strains, such as the Elstree virus, experience a drastic increase of virulence in the immunosuppressed organism (subjected to whole-body irradiation), the MVA virus cannot be activated not even in this situation."}
{"id": "PMID:219641", "title": "[Detection and persistence of human-pathogenic viruses in chemical sludge (author's transl)].", "content": "Virological investigations, using poliovirus type I, were carried out on the detection of enterovirus and their persistence in the chemical sludge from a tertiary treatment process, which could be suitable for agricultural and horticultural applications.--A comparison of six eluents showed that tryptose phosphate broth yielded best results allowing approximately 30% overall recovery with the method described. With sludge of low virus content a concentration was possible with alginate filters and the phase separation method.--Examinations on the persistence of poliovirus show that at 5 degrees C and 10 degrees C the inactivation was slow and that virus was detectable over a 15 week period at 5 degrees C.", "contents": "[Detection and persistence of human-pathogenic viruses in chemical sludge (author's transl)]. Virological investigations, using poliovirus type I, were carried out on the detection of enterovirus and their persistence in the chemical sludge from a tertiary treatment process, which could be suitable for agricultural and horticultural applications.--A comparison of six eluents showed that tryptose phosphate broth yielded best results allowing approximately 30% overall recovery with the method described. With sludge of low virus content a concentration was possible with alginate filters and the phase separation method.--Examinations on the persistence of poliovirus show that at 5 degrees C and 10 degrees C the inactivation was slow and that virus was detectable over a 15 week period at 5 degrees C."}
{"id": "PMID:219642", "title": "Isolation and biological characterization of an adenovirus of rhesus macaques.", "content": "The etiology of a disease in rhesus monkeys the main clinical manifestation of which was acute conjunctivitis of an epizootic character has been studied. The cytopathogenic agent well propagating in primarily trypsinized kidney cells of monkeys has been isolated when investigating the affected eye mucosa. It was not pathogenic for laboratory animals. The mean diameter of the virions is 75 nm, the buoyant density in CsCl is 1.34 g/cm3, the viral DNA density is 1.706 g/cm3. The biological properties and findings of physicochemical, electron-microscopic, and serologic investigations allow one to allocate the isolated agent to the SV-37 strain, a representative of the adenovirus group.", "contents": "Isolation and biological characterization of an adenovirus of rhesus macaques. The etiology of a disease in rhesus monkeys the main clinical manifestation of which was acute conjunctivitis of an epizootic character has been studied. The cytopathogenic agent well propagating in primarily trypsinized kidney cells of monkeys has been isolated when investigating the affected eye mucosa. It was not pathogenic for laboratory animals. The mean diameter of the virions is 75 nm, the buoyant density in CsCl is 1.34 g/cm3, the viral DNA density is 1.706 g/cm3. The biological properties and findings of physicochemical, electron-microscopic, and serologic investigations allow one to allocate the isolated agent to the SV-37 strain, a representative of the adenovirus group."}
{"id": "PMID:219643", "title": "Preparation and properties of a Met-tRNAf binding factor from rat liver and rat hepatoma.", "content": "A Met-tRNAf binding factor (IF-2) from the microsomal fraction of rat liver and rat hepatoma ascites cells was partially purified by ammonium sulphate fractionation, DEAE-cellulose and phosphocellulose chromatography. The factor binds [3H]Met-tRNAf only in the presence of either GTP or GMPPCP. Maximal binding takes place at 37 degrees C and in the absence of Mg++. The factor is specific for Met-tRNAf and does not bind Phe-tRNA from rat liver or from E. coli. The ternary complex [Met-tRNAf . IF-2 . GTP1 binds to 40 S ribosomal subunits from rat liver in the absence of mRNA or poly(A, G, U) without GTP hydrolysis. GDP as well as aurintricarboxylic acid inhibit the ternary complex formation. Both factors are rapidly inactivated by N-ethylmaleimide treatment and by preincubation at 45 degrees C. Heat inactivation is partially prevented by GTP and GDP. With regard to the functional properties there are no significant differences between IF-2 from normal liver and hepatoma cells. On the other hand heat denaturation compared to the rat liver factor, which may be due to differences in contaminating proteins.", "contents": "Preparation and properties of a Met-tRNAf binding factor from rat liver and rat hepatoma. A Met-tRNAf binding factor (IF-2) from the microsomal fraction of rat liver and rat hepatoma ascites cells was partially purified by ammonium sulphate fractionation, DEAE-cellulose and phosphocellulose chromatography. The factor binds [3H]Met-tRNAf only in the presence of either GTP or GMPPCP. Maximal binding takes place at 37 degrees C and in the absence of Mg++. The factor is specific for Met-tRNAf and does not bind Phe-tRNA from rat liver or from E. coli. The ternary complex [Met-tRNAf . IF-2 . GTP1 binds to 40 S ribosomal subunits from rat liver in the absence of mRNA or poly(A, G, U) without GTP hydrolysis. GDP as well as aurintricarboxylic acid inhibit the ternary complex formation. Both factors are rapidly inactivated by N-ethylmaleimide treatment and by preincubation at 45 degrees C. Heat inactivation is partially prevented by GTP and GDP. With regard to the functional properties there are no significant differences between IF-2 from normal liver and hepatoma cells. On the other hand heat denaturation compared to the rat liver factor, which may be due to differences in contaminating proteins."}
{"id": "PMID:219644", "title": "Identification of the soluble HVP-associated antigen of the lymphoblastoid cell line established from lymphomatous baboon (Papio hamadryas).", "content": "A new technique (indirect double immunodiffusion) for detection of EBV-associated soluble antigen and corresponding antibodies has been developed. This technique includes three steps: 1) simple double immunodiffusion with extracts of Raji cells (or other EBV-genome positive cells) and human sera containing antibodies against EBV-associated soluble antigen; 2) extensive washing and treatment with anti-human globulin; 3) extensive washing and treatment with tannic acid. Using this test it was shown that the soluble antigen indistinguishable from EBV-associated soluble antigen was present in KMPG-1 cells producing HVP.", "contents": "Identification of the soluble HVP-associated antigen of the lymphoblastoid cell line established from lymphomatous baboon (Papio hamadryas). A new technique (indirect double immunodiffusion) for detection of EBV-associated soluble antigen and corresponding antibodies has been developed. This technique includes three steps: 1) simple double immunodiffusion with extracts of Raji cells (or other EBV-genome positive cells) and human sera containing antibodies against EBV-associated soluble antigen; 2) extensive washing and treatment with anti-human globulin; 3) extensive washing and treatment with tannic acid. Using this test it was shown that the soluble antigen indistinguishable from EBV-associated soluble antigen was present in KMPG-1 cells producing HVP."}
{"id": "PMID:219645", "title": "Shuttles for translocation of NADH in isolated liver cells from fed rats during oxidation of xylitol.", "content": "Translocation of xylitol-derived NADH via malate-aspartate and alpha-glycerophosphate shuttles was studied in liver cells isolated from fed rats. In bicarbonate medium amino-oxyacetate, rotenone and antimycin A, were equally efficient in depressing the xylitol removal. Incubation of cells in nonbicarbonate medium did not affect the rate of xylitol removal. In this medium amino-oxyacetate and antimycin A, but not rotenone, inhibited xylitol removal. Xylitol inhibited the lactate accumulation found when the cells were incubated without any exogenous substrates. Glucose was the main end product of xylitol oxidation. In nonbicarbonate medium ketogenesis was high, whereas in bicarbonate medium a low rate of ketone body formation was found. Xylitol had no effect on the rate of ketone body formation in either medium tested. Xylitol markedly decreased the ATP and Pi contents of the cells, but no change in the ATP/ADP x Pi ratio or the rate of oxygen consumption was found. The results suggest that NADH formed during xylitol oxidation is translocated to the mitochondria mainly through the malate-aspartate shuttle and only when this shuttle is inhibited does the alpha-glycerophosphate shuttle transfer NADH. Intramitochondrial reactions which form NADH and FADH2 are also suggested to be important regulators of the activity of the alpha-glycerophosphate shuttle.", "contents": "Shuttles for translocation of NADH in isolated liver cells from fed rats during oxidation of xylitol. Translocation of xylitol-derived NADH via malate-aspartate and alpha-glycerophosphate shuttles was studied in liver cells isolated from fed rats. In bicarbonate medium amino-oxyacetate, rotenone and antimycin A, were equally efficient in depressing the xylitol removal. Incubation of cells in nonbicarbonate medium did not affect the rate of xylitol removal. In this medium amino-oxyacetate and antimycin A, but not rotenone, inhibited xylitol removal. Xylitol inhibited the lactate accumulation found when the cells were incubated without any exogenous substrates. Glucose was the main end product of xylitol oxidation. In nonbicarbonate medium ketogenesis was high, whereas in bicarbonate medium a low rate of ketone body formation was found. Xylitol had no effect on the rate of ketone body formation in either medium tested. Xylitol markedly decreased the ATP and Pi contents of the cells, but no change in the ATP/ADP x Pi ratio or the rate of oxygen consumption was found. The results suggest that NADH formed during xylitol oxidation is translocated to the mitochondria mainly through the malate-aspartate shuttle and only when this shuttle is inhibited does the alpha-glycerophosphate shuttle transfer NADH. Intramitochondrial reactions which form NADH and FADH2 are also suggested to be important regulators of the activity of the alpha-glycerophosphate shuttle."}
{"id": "PMID:219647", "title": "Electron microscopic detection of papilloma virus particles in selected koilocytotic cells in a routine cervical smear.", "content": "A routine cervical smear from a 56-year-old postmenopausal woman showed appearances indicative of papilloma virus infection with atypia. In an attempt to prove the diagnosis, the smear was reprocessed for electron microscopic examination. The reprocessing technique is described. Ultrastructural preservation was poor, and significant shrinkage was observed. In spite of these technical difficulties it was possible to prove that the selected cells in the smear contained papilloma virus particles. The virus particles seen were intranuclear in location and spherical in shape with a diameter of 40 to 50 nm. As was demonstrated in this case, the technique described will prove useful in evaluating the reliability of various diagnostic criteria for identifying viral infections in routine smears. This will apply particularly in cases where cultural confirmation of a reported viral infection is not possible.", "contents": "Electron microscopic detection of papilloma virus particles in selected koilocytotic cells in a routine cervical smear. A routine cervical smear from a 56-year-old postmenopausal woman showed appearances indicative of papilloma virus infection with atypia. In an attempt to prove the diagnosis, the smear was reprocessed for electron microscopic examination. The reprocessing technique is described. Ultrastructural preservation was poor, and significant shrinkage was observed. In spite of these technical difficulties it was possible to prove that the selected cells in the smear contained papilloma virus particles. The virus particles seen were intranuclear in location and spherical in shape with a diameter of 40 to 50 nm. As was demonstrated in this case, the technique described will prove useful in evaluating the reliability of various diagnostic criteria for identifying viral infections in routine smears. This will apply particularly in cases where cultural confirmation of a reported viral infection is not possible."}
{"id": "PMID:219648", "title": "Diagnosis of a papillary hidradenoma of the vulva by simultaneous cytology and colposcopy.", "content": "A case of papillary hidradenoma of the vulva is reported, and the simultaneous use of cytology and colposcopy as diagnostic aids is suggested. The cytologic and colposcopic findings are described in detail. The cytologic findings correspond with the histologic pattern of these benign growths.", "contents": "Diagnosis of a papillary hidradenoma of the vulva by simultaneous cytology and colposcopy. A case of papillary hidradenoma of the vulva is reported, and the simultaneous use of cytology and colposcopy as diagnostic aids is suggested. The cytologic and colposcopic findings are described in detail. The cytologic findings correspond with the histologic pattern of these benign growths."}
{"id": "PMID:219649", "title": "Malignant cystosarcoma phyllodes a case report with cytologic presentation.", "content": "The cytologic findings in a fine-needle aspirate of a malignant cystosarcoma phyllodes of the breast are presented. They are characterized by the presence of mononucleated and multinucleated sarcoma cells and clusters of normal or hyperplastic duct epithelial cells. The histogenesis and subclassification of the stromal portion of this rare neoplasm are discussed.", "contents": "Malignant cystosarcoma phyllodes a case report with cytologic presentation. The cytologic findings in a fine-needle aspirate of a malignant cystosarcoma phyllodes of the breast are presented. They are characterized by the presence of mononucleated and multinucleated sarcoma cells and clusters of normal or hyperplastic duct epithelial cells. The histogenesis and subclassification of the stromal portion of this rare neoplasm are discussed."}
{"id": "PMID:219653", "title": "Effects of prolonged infusions of potassium chloride, adrenocorticotrophin or angiotensin II upon serum aldosterone concentration and the conversion of corticosterone to aldosterone in rats.", "content": "The temporal relation between alterations in serum aldosterone and in the conversion of labelled corticosterone to aldosterone by incubated adrenal tissue was studied in conscious rats receiving long-term infusions of KCl, ACTH or angiotensin II. When potassium-deficient rats were given KCl, a marked increase in serum aldosterone was observed only after 12 h, i.e. at a time when the conversion of corticosterone to aldosterone had become normal. After 24 h of ACTH infusion into sodium- and potassium-replete rats the serum aldosterone was markedly elevated, whereas the conversion of corticosterone to aldosterone was significantly decreased. After 48 h of continued ACTH infusion the serum aldosterone returned to normal and there was a further decrease in the conversion rate. A 24-h angiotensin II infusion into sodium- and potassium-replete rats induced significant increases in both the serum aldosterone and the conversion. After 48 h of continued angiotensin infusion the serum aldosterone returned to normal while the conversion and the blood pressure remained elevated. These results indicate that the activity of the enzymes involved in the final steps of aldosterone biosynthesis may become rate-limiting for the secretion of aldosterone during potassium deficiency and during prolonged ACTH treatment. On the other hand, the observed transiency of aldosterone stimulation by exogenous angiotensin II was not due to a suppression of the final steps of aldosterone biosynthesis and remains unexplained.", "contents": "Effects of prolonged infusions of potassium chloride, adrenocorticotrophin or angiotensin II upon serum aldosterone concentration and the conversion of corticosterone to aldosterone in rats. The temporal relation between alterations in serum aldosterone and in the conversion of labelled corticosterone to aldosterone by incubated adrenal tissue was studied in conscious rats receiving long-term infusions of KCl, ACTH or angiotensin II. When potassium-deficient rats were given KCl, a marked increase in serum aldosterone was observed only after 12 h, i.e. at a time when the conversion of corticosterone to aldosterone had become normal. After 24 h of ACTH infusion into sodium- and potassium-replete rats the serum aldosterone was markedly elevated, whereas the conversion of corticosterone to aldosterone was significantly decreased. After 48 h of continued ACTH infusion the serum aldosterone returned to normal and there was a further decrease in the conversion rate. A 24-h angiotensin II infusion into sodium- and potassium-replete rats induced significant increases in both the serum aldosterone and the conversion. After 48 h of continued angiotensin infusion the serum aldosterone returned to normal while the conversion and the blood pressure remained elevated. These results indicate that the activity of the enzymes involved in the final steps of aldosterone biosynthesis may become rate-limiting for the secretion of aldosterone during potassium deficiency and during prolonged ACTH treatment. On the other hand, the observed transiency of aldosterone stimulation by exogenous angiotensin II was not due to a suppression of the final steps of aldosterone biosynthesis and remains unexplained."}
{"id": "PMID:219650", "title": "Metabolic effects of glucagon in endogenous hypertriglyceridemia.", "content": "The metabolic effects of glucagon, administered i.v. in doses of 1 microgram/kg, were evaluated in two groups of patients with endogenous hypertriglyceridemia (Types IV and V according to Fredrickson) with normal and reduced glucose tolerance and in a control group. Glucagon had a lipolytic effect, evaluated as the plasma increase of free fatty acids (FFA) during the first 20 min in normal subjects, but not in the two hyperlipemic groups. A negative correlation was observed between fasting IRI level and FFA mobilization. The ketogenic and hypotriglyceridemic effects of glucagon were demonstrated in normal and hyperlipemic groups. It would seem, therefore, that at the pharmacological doses injected, there is no resistance to the hypotriglyceridemic effect of glucagon in endogenous hypertriglyceridemia.", "contents": "Metabolic effects of glucagon in endogenous hypertriglyceridemia. The metabolic effects of glucagon, administered i.v. in doses of 1 microgram/kg, were evaluated in two groups of patients with endogenous hypertriglyceridemia (Types IV and V according to Fredrickson) with normal and reduced glucose tolerance and in a control group. Glucagon had a lipolytic effect, evaluated as the plasma increase of free fatty acids (FFA) during the first 20 min in normal subjects, but not in the two hyperlipemic groups. A negative correlation was observed between fasting IRI level and FFA mobilization. The ketogenic and hypotriglyceridemic effects of glucagon were demonstrated in normal and hyperlipemic groups. It would seem, therefore, that at the pharmacological doses injected, there is no resistance to the hypotriglyceridemic effect of glucagon in endogenous hypertriglyceridemia."}
{"id": "PMID:219651", "title": "Changes in mitochondrial redox state following an oral glucose load.", "content": "Changes in cytosol and mitochondrial redox state after an oral glucose load were studied in the liver of rats. The [NAD+]/[NADH] ratios increased 4-fold in the cytoplasm and 1.5-fold in the mitochondria 60 min after an oral glucose load, when serum IRI was maximally increased. It is suggested that an increase in mitochondrial redox state following an oral glucose load is due to an enhanced rate of removal of NADH by the respiratory chain, possibly due to an elevated level of insulin available to hepatocytes, and that an increase in cytosol redox state depends on an enhancement in mitochondrial oxidation of cytosol reducing equivalent.", "contents": "Changes in mitochondrial redox state following an oral glucose load. Changes in cytosol and mitochondrial redox state after an oral glucose load were studied in the liver of rats. The [NAD+]/[NADH] ratios increased 4-fold in the cytoplasm and 1.5-fold in the mitochondria 60 min after an oral glucose load, when serum IRI was maximally increased. It is suggested that an increase in mitochondrial redox state following an oral glucose load is due to an enhanced rate of removal of NADH by the respiratory chain, possibly due to an elevated level of insulin available to hepatocytes, and that an increase in cytosol redox state depends on an enhancement in mitochondrial oxidation of cytosol reducing equivalent."}
{"id": "PMID:219655", "title": "[Comparative histoenzymological demonstration of certain digestive enzymes in the intestinal epithelium of the mouse and the chicken during a 24-h-period (author's transl)].", "content": "At different times of the day activities of hydrolytic (alkaline and acid phosphatase, esterase) and oxydative (succinodehydrogenase, cytochromoxidase, monoaminoxidase) enzymes were studied in the epithelium of the upper part of the jejunum in the adult female mouse and the adult laying chicken. In both species the activities of the intestinal enzymes showed marked circadian variations with respect to their activity and distribution pattern. The variations did not principally differ in both species. The species' differences were mainly expressed by phase shifts of about 12 h in the occurrence of maximal and minimal activities according to the different phases of the locomotor activity of the mainly night-active mice and day-active chickens.", "contents": "[Comparative histoenzymological demonstration of certain digestive enzymes in the intestinal epithelium of the mouse and the chicken during a 24-h-period (author's transl)]. At different times of the day activities of hydrolytic (alkaline and acid phosphatase, esterase) and oxydative (succinodehydrogenase, cytochromoxidase, monoaminoxidase) enzymes were studied in the epithelium of the upper part of the jejunum in the adult female mouse and the adult laying chicken. In both species the activities of the intestinal enzymes showed marked circadian variations with respect to their activity and distribution pattern. The variations did not principally differ in both species. The species' differences were mainly expressed by phase shifts of about 12 h in the occurrence of maximal and minimal activities according to the different phases of the locomotor activity of the mainly night-active mice and day-active chickens."}
{"id": "PMID:219652", "title": "The effect of acute alloxan diabetes on the sensitivity of the rat skeletal neuromuscular junction to drugs.", "content": "Preparations from alloxan diabetic rats showed a reduced sensitivity to the neuromuscular blocking action of (+)-tubocurarine but no alteration in sensitivity to the depolarizing neuromuscular blocking drug decamethonium. Physostigmine was less effective in augmenting twitch height in preparations from alloxan diabetic rats and such preparations had a significantly lowered total cholinesterase activity compared with control preparations. An additional observation was a reduction in the effectiveness of the pre-junctionally active agent beta-bungarotoxin in producing neuromuscular blockade in physostigmine-treated preparations from alloxan diabetic rats. All the changes produced by alloxan administration were prevented by treatment with insulin.", "contents": "The effect of acute alloxan diabetes on the sensitivity of the rat skeletal neuromuscular junction to drugs. Preparations from alloxan diabetic rats showed a reduced sensitivity to the neuromuscular blocking action of (+)-tubocurarine but no alteration in sensitivity to the depolarizing neuromuscular blocking drug decamethonium. Physostigmine was less effective in augmenting twitch height in preparations from alloxan diabetic rats and such preparations had a significantly lowered total cholinesterase activity compared with control preparations. An additional observation was a reduction in the effectiveness of the pre-junctionally active agent beta-bungarotoxin in producing neuromuscular blockade in physostigmine-treated preparations from alloxan diabetic rats. All the changes produced by alloxan administration were prevented by treatment with insulin."}
{"id": "PMID:219658", "title": "Farber's disease (disseminated lipogranulomatosis)--a pathological, histochemical and ultrastructural study--.", "content": "The first case of Farber's disease in Japan was reported, which was confirmed clinically, biochemically and pathologically. Soon after birth, the patient started developing hoarseness, stridor, fever, muscle hypotonous with retarded psychomotor functions including incapability of sitting alone and head control, joint swelling, subcutaneous nodules, albuminocytologic dissociation in cerebrospinal fluid, nodular corneal opacity, and abnormal findings in electroencephalogram. Lipid analysis on the material obtained from a subcutaneous nodule confirmed the presence of ceramide. Pathologically, the subcutanoues nodules were made up of granulomatous lesions displaying varied histological pictures, i.e., from cellular to fibrous areas depending on the disease progress. In the beginning, cells were mostly spindle-shaped, and as these cells were getting more round and larger, cells manifested the morphology of foam cells. Spindle-shaped cells were positive for periodic acid-Schiff and acid mucopolysaccharide stainings. This particular substance disappeared almost entirely in typical foam cells. Electron microscopically, the cytoplasm of foam cells was filled with membrane-bound storage inclusions which consisted of so-called curvilinear tubular structures. Morphogenesis of the granulomatous lesions and histochemical and ultrastructural correlation of storage cells in this disorder were discussed.", "contents": "Farber's disease (disseminated lipogranulomatosis)--a pathological, histochemical and ultrastructural study--. The first case of Farber's disease in Japan was reported, which was confirmed clinically, biochemically and pathologically. Soon after birth, the patient started developing hoarseness, stridor, fever, muscle hypotonous with retarded psychomotor functions including incapability of sitting alone and head control, joint swelling, subcutaneous nodules, albuminocytologic dissociation in cerebrospinal fluid, nodular corneal opacity, and abnormal findings in electroencephalogram. Lipid analysis on the material obtained from a subcutaneous nodule confirmed the presence of ceramide. Pathologically, the subcutanoues nodules were made up of granulomatous lesions displaying varied histological pictures, i.e., from cellular to fibrous areas depending on the disease progress. In the beginning, cells were mostly spindle-shaped, and as these cells were getting more round and larger, cells manifested the morphology of foam cells. Spindle-shaped cells were positive for periodic acid-Schiff and acid mucopolysaccharide stainings. This particular substance disappeared almost entirely in typical foam cells. Electron microscopically, the cytoplasm of foam cells was filled with membrane-bound storage inclusions which consisted of so-called curvilinear tubular structures. Morphogenesis of the granulomatous lesions and histochemical and ultrastructural correlation of storage cells in this disorder were discussed."}
{"id": "PMID:219659", "title": "Electron microscopic studies of the effect of ACTH and flavin-adenine dinucleotide on adrenocortical atrophy of rats treated with dexamethasone phosphate.", "content": "In a previous paper the authors described the morphologic observations that the concomitant administration of ACTH and flavin-adenine dinucleotide (FAD) to hypophysectomized rats exerted a more potent preventive effect on atrophy of the adrenal cortex of the animals than the single administration of ACTH. The present study was made to electron-microscopically observe the effect of concomitant administration of ACTH and FAD on atrophy of the adrenal cortex induced with the administration of dexamethasone (Dx). The zona fasciculata of the adrenal gland of rats treated with Dx+ACTH+FAD was morphologically closer in cell organelles such as smooth-surfaced endoplasmic reticulum, mitochondria and chylomicrons to that of control animals than the counterpart of animals treated with Dx+ACTH only. The zona fasciculata of the adrenal cortex of animals treated with Dx+FAD was morphologically similar to that of animals treated with Dx only. These findings suggested that FAD would potentiate the adrenocorticotropic action of ACTH through its physiologic action.", "contents": "Electron microscopic studies of the effect of ACTH and flavin-adenine dinucleotide on adrenocortical atrophy of rats treated with dexamethasone phosphate. In a previous paper the authors described the morphologic observations that the concomitant administration of ACTH and flavin-adenine dinucleotide (FAD) to hypophysectomized rats exerted a more potent preventive effect on atrophy of the adrenal cortex of the animals than the single administration of ACTH. The present study was made to electron-microscopically observe the effect of concomitant administration of ACTH and FAD on atrophy of the adrenal cortex induced with the administration of dexamethasone (Dx). The zona fasciculata of the adrenal gland of rats treated with Dx+ACTH+FAD was morphologically closer in cell organelles such as smooth-surfaced endoplasmic reticulum, mitochondria and chylomicrons to that of control animals than the counterpart of animals treated with Dx+ACTH only. The zona fasciculata of the adrenal cortex of animals treated with Dx+FAD was morphologically similar to that of animals treated with Dx only. These findings suggested that FAD would potentiate the adrenocorticotropic action of ACTH through its physiologic action."}
{"id": "PMID:219660", "title": "Syndrome of the sea-blue histiocyte--the first case report in Japan and review of the literature--.", "content": "A case of the syndrome of sea-blue histiocyte is presented in a 53-year-old Japanese woman, which is the first recorded case in Japan. The patient had hepatosplenomegaly, bleeding manifestations, mild thrombocytopenia, fatty metamorphosis and cirrhosis of the liver, as well as abnormal serum lipid profiles. Her parents were consanguineous and her maternal grandmother with hepatomegaly died of hepatic failure. Histologically, peculiar histiocytes containing numerous, intracytoplasmic sea-blue stained granules on May-Giemsa stain were demonstrated in biopsy materials of the bone marrow, lymph node and liver. The sea-blue granules in these histiocytes proved to have histochemical staining characteristics of lipogenic ceroid-like pigment. Ultrastructurally, these granules showed membrane-bound, pleomorphic inclusions of heterogeneous nature, including electron-dense amorphous or variegatedly osmiophilic, frequently laminated materials. Enzyme cytochemically, localization of acid phosphatase activity was demonstrated in and around the intracytoplasmic inclusions. With regard to the pathogenesis of the sea-blue histiocytes in this case, it may be suggested that the existence of the abnormality in lipid metabolism plays an important role in intralysosomal ceroidogenesis in these histiocytes.", "contents": "Syndrome of the sea-blue histiocyte--the first case report in Japan and review of the literature--. A case of the syndrome of sea-blue histiocyte is presented in a 53-year-old Japanese woman, which is the first recorded case in Japan. The patient had hepatosplenomegaly, bleeding manifestations, mild thrombocytopenia, fatty metamorphosis and cirrhosis of the liver, as well as abnormal serum lipid profiles. Her parents were consanguineous and her maternal grandmother with hepatomegaly died of hepatic failure. Histologically, peculiar histiocytes containing numerous, intracytoplasmic sea-blue stained granules on May-Giemsa stain were demonstrated in biopsy materials of the bone marrow, lymph node and liver. The sea-blue granules in these histiocytes proved to have histochemical staining characteristics of lipogenic ceroid-like pigment. Ultrastructurally, these granules showed membrane-bound, pleomorphic inclusions of heterogeneous nature, including electron-dense amorphous or variegatedly osmiophilic, frequently laminated materials. Enzyme cytochemically, localization of acid phosphatase activity was demonstrated in and around the intracytoplasmic inclusions. With regard to the pathogenesis of the sea-blue histiocytes in this case, it may be suggested that the existence of the abnormality in lipid metabolism plays an important role in intralysosomal ceroidogenesis in these histiocytes."}
{"id": "PMID:219661", "title": "Density determinations of human parathyroid glands by density gradients.", "content": "The densities of human parathyroid glands were measured in density gradient columns of various media. Percoll (an aqueous colloidal solution of polyvinylpyrrolidone-coated silica), equilibrated to 300 mOsm with sodium chloride, was found to be the ideal gradient medium for density measurements of tissues with a density greater than 1.0 g/ml. which includes most parathyroid glands. The densities of the glands varied between 0.96 and 1.06 g/ml. Density measurements in gradients of Percoll were simple and reproducible and were made with an accuracy of approximately 0.001 g/ml. In other gradient media (aqueous solutions of sucrose and Ficoll, and organic solvents) there was a drift in density caused by osmotic or lipid-solving effects of the media. For measurements of densities less than 1.0 g/ml no ideal gradient medium was found, but a silicon oil or carbon tetrachloride/kerosone gradient could be used with somewhat reduced accuracy. It is concluded that the density gradient technique with the use of Percoll is potentially useful as a complement to routine histopathological parathyroid diagnosis, as glandular density is a good indicator of the relative proportions of parenchymal and fat tissue.", "contents": "Density determinations of human parathyroid glands by density gradients. The densities of human parathyroid glands were measured in density gradient columns of various media. Percoll (an aqueous colloidal solution of polyvinylpyrrolidone-coated silica), equilibrated to 300 mOsm with sodium chloride, was found to be the ideal gradient medium for density measurements of tissues with a density greater than 1.0 g/ml. which includes most parathyroid glands. The densities of the glands varied between 0.96 and 1.06 g/ml. Density measurements in gradients of Percoll were simple and reproducible and were made with an accuracy of approximately 0.001 g/ml. In other gradient media (aqueous solutions of sucrose and Ficoll, and organic solvents) there was a drift in density caused by osmotic or lipid-solving effects of the media. For measurements of densities less than 1.0 g/ml no ideal gradient medium was found, but a silicon oil or carbon tetrachloride/kerosone gradient could be used with somewhat reduced accuracy. It is concluded that the density gradient technique with the use of Percoll is potentially useful as a complement to routine histopathological parathyroid diagnosis, as glandular density is a good indicator of the relative proportions of parenchymal and fat tissue."}
{"id": "PMID:219662", "title": "Neutralization of aggregated strains of enterovirus 71 and echovirus type 4 in RD and Vero or GMK-AH1 cells.", "content": "Strains of enterovirus 71 and echovirus type 4 containing aggregates which were poorly neutralized by antibody in cell lines of green monkey kidney origin such as Vero and GMK-AH1, were as easily neutralized as non-aggregated strains when grown in human RD cells, The explanation for this may be a lesser degree of aggregation of viral materials originating from RD cells and/or the use of lower doses of virus for neutralization tests in such cells. The latter was a consequence of a higher sensitivity of RD cells to minimal amounts of virus than that shown by Vero and GMK-AH1 cells. Thus, virus grown in RD, Vero or GMK-AH1 cells reached a titre 10 to 100 times higher in RD cells than in the other cell lines.", "contents": "Neutralization of aggregated strains of enterovirus 71 and echovirus type 4 in RD and Vero or GMK-AH1 cells. Strains of enterovirus 71 and echovirus type 4 containing aggregates which were poorly neutralized by antibody in cell lines of green monkey kidney origin such as Vero and GMK-AH1, were as easily neutralized as non-aggregated strains when grown in human RD cells, The explanation for this may be a lesser degree of aggregation of viral materials originating from RD cells and/or the use of lower doses of virus for neutralization tests in such cells. The latter was a consequence of a higher sensitivity of RD cells to minimal amounts of virus than that shown by Vero and GMK-AH1 cells. Thus, virus grown in RD, Vero or GMK-AH1 cells reached a titre 10 to 100 times higher in RD cells than in the other cell lines."}
{"id": "PMID:219664", "title": "Effect of di-(2-ethylhexyl) phthalate on rat liver injured by chronic carbon tetrachloride treatment.", "content": "The effect of Di-(2-ethylhexyl) phthalate (DEPH), a widely used plasticizer, was studied using histopathological and biochemical parameters on rat liver injured by carbon tetrachloride (CCl4). The mild centrilobular necrosis observed with CCl4 (7.7 mmol/kg subcutaneously and biweekly up to 38 days) and mild congestion and bile duct proliferation produced by DEHP (2.5 mmol/kg intraperitoneally daily for ten days after the day 28 of experiment) were modified into extensive necrosis of the parenchymal cells when the animals received both chemicals. Groups of hepatocytes mostly at the periphery of the lobules also showed coagulative necrosis and some central and portal veins were completely occluded. Alterations in the activity of serum and liver enzymes of the animals receiving both chemicals were not significantly different from those treated with CCl4 alone, except in case of glucose-6-phosphatase (G-6Pase) and SGPT. The characteristic decrease of G-6-Pase and increase of SGPT was less marked. Although the exact mechanism of the chemical interaction between CCl4 and DEHP is not known, the results indicate their combined toxic potentiality.", "contents": "Effect of di-(2-ethylhexyl) phthalate on rat liver injured by chronic carbon tetrachloride treatment. The effect of Di-(2-ethylhexyl) phthalate (DEPH), a widely used plasticizer, was studied using histopathological and biochemical parameters on rat liver injured by carbon tetrachloride (CCl4). The mild centrilobular necrosis observed with CCl4 (7.7 mmol/kg subcutaneously and biweekly up to 38 days) and mild congestion and bile duct proliferation produced by DEHP (2.5 mmol/kg intraperitoneally daily for ten days after the day 28 of experiment) were modified into extensive necrosis of the parenchymal cells when the animals received both chemicals. Groups of hepatocytes mostly at the periphery of the lobules also showed coagulative necrosis and some central and portal veins were completely occluded. Alterations in the activity of serum and liver enzymes of the animals receiving both chemicals were not significantly different from those treated with CCl4 alone, except in case of glucose-6-phosphatase (G-6Pase) and SGPT. The characteristic decrease of G-6-Pase and increase of SGPT was less marked. Although the exact mechanism of the chemical interaction between CCl4 and DEHP is not known, the results indicate their combined toxic potentiality."}
{"id": "PMID:219672", "title": "Primary and metastatic scirrrhous carcinoma of the rectum.", "content": "Eight cases of scirrhous carcinoma of the rectum are described. Five patients had primary lesions and three had metastases from stomach and breast. Radiographic features were severe rectal narrowing, rigidity, and smooth contours or, more commonly, moderate narrowing, distorted nodular folds, and an irregular serrated contour mimicking inflammatory disease. Difficulties in the radiologic and histologic diagnosis and a short review of pertinent literature are reported.", "contents": "Primary and metastatic scirrrhous carcinoma of the rectum. Eight cases of scirrhous carcinoma of the rectum are described. Five patients had primary lesions and three had metastases from stomach and breast. Radiographic features were severe rectal narrowing, rigidity, and smooth contours or, more commonly, moderate narrowing, distorted nodular folds, and an irregular serrated contour mimicking inflammatory disease. Difficulties in the radiologic and histologic diagnosis and a short review of pertinent literature are reported."}
{"id": "PMID:219674", "title": "Prognostic value of a persistently positive technetium-99m stannous pyrophosphate myocardial scintigram after myocardial infarction.", "content": "Technetium-99m stannous pyrophosphate myocardial scintigrams were obtained in 138 clinically stable patients 32.7 +/- 47.3 weeks (range 6 to 260) after acute myocardial infarction. Of the 138 patients, 74 (54 percent) had a persistently positive scintigram. Patients with such a scintigram were more likely to have severe angina pectoris, compensated congestive heart failure, anterior location of acute myocardial infarction, Q waves and S-T segment elevation in the electrocardiograms, cardiomegaly, left ventricular dyssynergy (dyskinesia or global dyssynergy), and an ejection fraction of less than 50 percent. During a follow-up period of 11.6 +/- 6.9 months after scintigraphy, 42 percent of the patients with a persistently positive scintigram had either a cardiac death, a nonfatal myocardial infarction, unstable angina pectoris or decompensated congestive heart failure compared with 13 percent of the patients with a negative scintigram (P less than 0.001). Of the 14 patients with cardiac death, 13 (93 percent) had a persistently positive scintigram. A persistently positive scintigram not only was the best single predictor of cardiac death and combined end points, but also added significantly to the predictive ability of the other clinical variables, including age, location of acute myocardial infarct, clinical status, electrocardiographic findings, and chest X-ray findings. It is concluded that technetium-99m stannous pyrophosphate myocardial scintigraphy has prognostic value in patients after acute myocardial infarction.", "contents": "Prognostic value of a persistently positive technetium-99m stannous pyrophosphate myocardial scintigram after myocardial infarction. Technetium-99m stannous pyrophosphate myocardial scintigrams were obtained in 138 clinically stable patients 32.7 +/- 47.3 weeks (range 6 to 260) after acute myocardial infarction. Of the 138 patients, 74 (54 percent) had a persistently positive scintigram. Patients with such a scintigram were more likely to have severe angina pectoris, compensated congestive heart failure, anterior location of acute myocardial infarction, Q waves and S-T segment elevation in the electrocardiograms, cardiomegaly, left ventricular dyssynergy (dyskinesia or global dyssynergy), and an ejection fraction of less than 50 percent. During a follow-up period of 11.6 +/- 6.9 months after scintigraphy, 42 percent of the patients with a persistently positive scintigram had either a cardiac death, a nonfatal myocardial infarction, unstable angina pectoris or decompensated congestive heart failure compared with 13 percent of the patients with a negative scintigram (P less than 0.001). Of the 14 patients with cardiac death, 13 (93 percent) had a persistently positive scintigram. A persistently positive scintigram not only was the best single predictor of cardiac death and combined end points, but also added significantly to the predictive ability of the other clinical variables, including age, location of acute myocardial infarct, clinical status, electrocardiographic findings, and chest X-ray findings. It is concluded that technetium-99m stannous pyrophosphate myocardial scintigraphy has prognostic value in patients after acute myocardial infarction."}
{"id": "PMID:219675", "title": "Changes in the fine structure of tanycytes during the annual reproductive cycle of the male little brown bat Myotis lucifugus lucifugus.", "content": "The hypothalamic arcuate nucleus in the male little brown bat Myotis lucifugus lucifugus was studied with the electron microscope. Animals were killed by intracardial perfusion at each season throughout the year so that the arcuate nucleus could be examined for seasonal variations in morphology. Striking seasonal changes in the fine structure of ependymal tanycytes lining the arcuate nucleus were observed. Tanycytes in animals collected in the fall and early winter exhibited pale processes characterized by a scant internal framework of microtubules and fine filaments. These processes, which were found throughout the arcuate nucleus, exhibited simple irregular shapes. In animals collected between January and June, tanycyte processes contained dense accumulations of fine filaments intermingled with microtubules, and projected long attenuated extensions that often formed multilamellar sheets around axodendritic terminals or other neuronal elements. Tanycyte processes of animals collected in July and August were densely packed with microtubules and fine filaments. The processes radiated elaborate multilamellar extensions that encapsulated axons, dendrites and even entire neuronal perikarya. Multilamellar sheets consisted of as many as 10 or 12 closely spaced gyres. The seasonal variations in tanycyte structure are suggestive of astrocyte-like behaviour. These changes are discussed with respect to seasonal changes in hypothalamic neuroendocrine activity.", "contents": "Changes in the fine structure of tanycytes during the annual reproductive cycle of the male little brown bat Myotis lucifugus lucifugus. The hypothalamic arcuate nucleus in the male little brown bat Myotis lucifugus lucifugus was studied with the electron microscope. Animals were killed by intracardial perfusion at each season throughout the year so that the arcuate nucleus could be examined for seasonal variations in morphology. Striking seasonal changes in the fine structure of ependymal tanycytes lining the arcuate nucleus were observed. Tanycytes in animals collected in the fall and early winter exhibited pale processes characterized by a scant internal framework of microtubules and fine filaments. These processes, which were found throughout the arcuate nucleus, exhibited simple irregular shapes. In animals collected between January and June, tanycyte processes contained dense accumulations of fine filaments intermingled with microtubules, and projected long attenuated extensions that often formed multilamellar sheets around axodendritic terminals or other neuronal elements. Tanycyte processes of animals collected in July and August were densely packed with microtubules and fine filaments. The processes radiated elaborate multilamellar extensions that encapsulated axons, dendrites and even entire neuronal perikarya. Multilamellar sheets consisted of as many as 10 or 12 closely spaced gyres. The seasonal variations in tanycyte structure are suggestive of astrocyte-like behaviour. These changes are discussed with respect to seasonal changes in hypothalamic neuroendocrine activity."}
{"id": "PMID:219677", "title": "Effect of a standardized wheat bran preparation on serum lipids in young healthy males.", "content": "Feeding of a chemically standardized coarse wheat bran product in a dose of 0.5 g/kg body weight per day over a period of 4 weeks in young healthy male volunteers did cause a significant reduction in total serum cholesterol as well as in total serum triglycerides of 10 and 24%, respectively. Very low density lipoprotein-, high density lipoprotein-, and low density lipoprotein-cholesterol levels tended to diminish during bran feeding. The most marked reduction was observed in the high density lipoprotein- cholesterol fraction. Although the duration of this study was relatively short, it is concluded, that these results could have therapeutic consequences for the dietary management of hyperlipidemia. However, the lowering of high density lipoprotein-cholesterol could also be interpreted as unfavorable since an inverse relationship between high density lipoprotien-cholesterol levels and the occurrence of coronary heart disease has been established.", "contents": "Effect of a standardized wheat bran preparation on serum lipids in young healthy males. Feeding of a chemically standardized coarse wheat bran product in a dose of 0.5 g/kg body weight per day over a period of 4 weeks in young healthy male volunteers did cause a significant reduction in total serum cholesterol as well as in total serum triglycerides of 10 and 24%, respectively. Very low density lipoprotein-, high density lipoprotein-, and low density lipoprotein-cholesterol levels tended to diminish during bran feeding. The most marked reduction was observed in the high density lipoprotein- cholesterol fraction. Although the duration of this study was relatively short, it is concluded, that these results could have therapeutic consequences for the dietary management of hyperlipidemia. However, the lowering of high density lipoprotein-cholesterol could also be interpreted as unfavorable since an inverse relationship between high density lipoprotien-cholesterol levels and the occurrence of coronary heart disease has been established."}
{"id": "PMID:219678", "title": "The effect of coffee consumption on plasma lipids, lipoproteins, and the development of aortic atherosclerosis in rhesus monkeys fed an atherogenic diet.", "content": "Rhesus monkeys (seven females and six males) were fed ad libitum a diet comparable to that consumed by humans, containing 25% by weight fat (40% of calories) and 0.15% cholesterol (0.3 mg/kcal) for 12 months (phase 1). From the 13th month all monkeys were continued on the diet while four females and three males were given 50% coffee as their fluid intake and the remainder were water controls (phase 2). Major changes in total plasma lipids and lipoprotein profiles occurred within 3 months and generally plateaued thereafter. Total plasma protein remained constant while total plasma cholesterol, phospholipids, triglycerides, and free fatty acid levels increased. After the initiation of coffee, there was no difference between the diet-water group and the diet-coffee group with respect to total protein and lipids in plasma. Total concentrations of plasma lipoproteins varied throughout the study. The pre-beta (very low density lipoproteins) fraction remained constant while the beta (low density lipoprotein) and alpha (high density lipoprotein) fractions, along with their major components, increased within 3 to 6 months, then fluctuated in absolute weight thereafter. The introduction of 50% coffee was without effect on the dynamic changes in these fractions as fluctuations were found in both groups and to the same magnitude. This leads the authors to suspect that such variations are \"normal\" or are in response to the diet per se. The atherogenic diet induced fatty streaks in the aortas of all monkeys to a greater extent in males than females. However, there were no gross differences in the quantity or distribution of the streaks between control and coffee-drinking monkeys.", "contents": "The effect of coffee consumption on plasma lipids, lipoproteins, and the development of aortic atherosclerosis in rhesus monkeys fed an atherogenic diet. Rhesus monkeys (seven females and six males) were fed ad libitum a diet comparable to that consumed by humans, containing 25% by weight fat (40% of calories) and 0.15% cholesterol (0.3 mg/kcal) for 12 months (phase 1). From the 13th month all monkeys were continued on the diet while four females and three males were given 50% coffee as their fluid intake and the remainder were water controls (phase 2). Major changes in total plasma lipids and lipoprotein profiles occurred within 3 months and generally plateaued thereafter. Total plasma protein remained constant while total plasma cholesterol, phospholipids, triglycerides, and free fatty acid levels increased. After the initiation of coffee, there was no difference between the diet-water group and the diet-coffee group with respect to total protein and lipids in plasma. Total concentrations of plasma lipoproteins varied throughout the study. The pre-beta (very low density lipoproteins) fraction remained constant while the beta (low density lipoprotein) and alpha (high density lipoprotein) fractions, along with their major components, increased within 3 to 6 months, then fluctuated in absolute weight thereafter. The introduction of 50% coffee was without effect on the dynamic changes in these fractions as fluctuations were found in both groups and to the same magnitude. This leads the authors to suspect that such variations are \"normal\" or are in response to the diet per se. The atherogenic diet induced fatty streaks in the aortas of all monkeys to a greater extent in males than females. However, there were no gross differences in the quantity or distribution of the streaks between control and coffee-drinking monkeys."}
{"id": "PMID:219681", "title": "Studies on the quality of breast milk during 23 months of lactation in a rural community of the Ivory Coast.", "content": "Milk samples from 33 women from a rural area of the Ivory Coast were analyzed once a month. In two longitudinal studies covering 23 months of breast feeding, analyses of lipid components and protein were performed. The compositions remained virtually constant over 23 months of lactation except for a decrease of protein concentration during the first 6 months, a rising trend of myristic acid (14:0) and a falling trend of oleic acid (18:1). Infants were growing well on breast milk with nothing else for the first 5 months, but thereafter their growth curves were no longer satisfactory as judged by Western standards: weight for age (percentage of Harvard standards) decreased from 5 to 10 months of age to level off thereafter at a value of 80%. The mothers' weight for height remained constant. In a cross-sectional study, additional determinations were performed: aminograms, lactose, calories, iron, copper, manganese, zinc, and vitamin E. All data were compared with those of the literature. Lauric (12:0) and myristic (14:0) acids were higher, total lipids and polyunsaturated fatty acids lower than those published for Western countries. Plasma composition of the mothers showed lower levels of albumin, lipids, and polyunsaturated fatty acids as well as blood hemoglobin. Possible correlations between various variables such as milk composition, plasma levels, and anthropometry were calculated and discussed.", "contents": "Studies on the quality of breast milk during 23 months of lactation in a rural community of the Ivory Coast. Milk samples from 33 women from a rural area of the Ivory Coast were analyzed once a month. In two longitudinal studies covering 23 months of breast feeding, analyses of lipid components and protein were performed. The compositions remained virtually constant over 23 months of lactation except for a decrease of protein concentration during the first 6 months, a rising trend of myristic acid (14:0) and a falling trend of oleic acid (18:1). Infants were growing well on breast milk with nothing else for the first 5 months, but thereafter their growth curves were no longer satisfactory as judged by Western standards: weight for age (percentage of Harvard standards) decreased from 5 to 10 months of age to level off thereafter at a value of 80%. The mothers' weight for height remained constant. In a cross-sectional study, additional determinations were performed: aminograms, lactose, calories, iron, copper, manganese, zinc, and vitamin E. All data were compared with those of the literature. Lauric (12:0) and myristic (14:0) acids were higher, total lipids and polyunsaturated fatty acids lower than those published for Western countries. Plasma composition of the mothers showed lower levels of albumin, lipids, and polyunsaturated fatty acids as well as blood hemoglobin. Possible correlations between various variables such as milk composition, plasma levels, and anthropometry were calculated and discussed."}
{"id": "PMID:219682", "title": "A nonencapsulated sclerosing lesion of the breast.", "content": "A histological study of 15 examples of a unique proliferative and tubular lesion (Fenoglio and Lattes) of the breast was performed. Although it consistently lacked infiltration of adipose tissue, the commonality of some of its morphologic features and those of tubular cancer provokes the possibility that these lesions may represent incipient tubular cancers. Nevertheless, such lesions may be satisfactorily treated by simple excision. Since we are certain only about its topographic and clinical behavior, but not its precise biologic nature, we regard the designation nonencapsulated sclerosing lesion most appropriate. Stromal and periductal elastosis was not infrequently encountered in examples of overt sclerosing and blunt ductal adenosis which may mimic, but can readily be distinguished from, the nonencapsulated sclerosing lesion.", "contents": "A nonencapsulated sclerosing lesion of the breast. A histological study of 15 examples of a unique proliferative and tubular lesion (Fenoglio and Lattes) of the breast was performed. Although it consistently lacked infiltration of adipose tissue, the commonality of some of its morphologic features and those of tubular cancer provokes the possibility that these lesions may represent incipient tubular cancers. Nevertheless, such lesions may be satisfactorily treated by simple excision. Since we are certain only about its topographic and clinical behavior, but not its precise biologic nature, we regard the designation nonencapsulated sclerosing lesion most appropriate. Stromal and periductal elastosis was not infrequently encountered in examples of overt sclerosing and blunt ductal adenosis which may mimic, but can readily be distinguished from, the nonencapsulated sclerosing lesion."}
{"id": "PMID:219683", "title": "Adenovirus hepatitis in an immunosuppressed adult patient.", "content": "The role of adenovirus as an etiologic agent of hepatic damage has been controversial. A fatal case of adenovirus infection with fulminant hepatitis in a young immunosuppressed adult patient is presented. Intranuclear inclusions were confined to the liver. Electron microscopy revealed crystalline arrays of virions within hepatocytes. This is apparently the first reported case of adenovirus hepatitis occurring in an adult. Adenovirus hepatitis represents another hazard for the immunosuppressed patient.", "contents": "Adenovirus hepatitis in an immunosuppressed adult patient. The role of adenovirus as an etiologic agent of hepatic damage has been controversial. A fatal case of adenovirus infection with fulminant hepatitis in a young immunosuppressed adult patient is presented. Intranuclear inclusions were confined to the liver. Electron microscopy revealed crystalline arrays of virions within hepatocytes. This is apparently the first reported case of adenovirus hepatitis occurring in an adult. Adenovirus hepatitis represents another hazard for the immunosuppressed patient."}
{"id": "PMID:219685", "title": "Acquired cytomegalovirus infection in preterm infants.", "content": "Small sick preterm infants requiring care in a neonatal intensive care unit for more than 28 days were cultured for cytomegalovirus in urine and/or nasopharynx during two periods lasting a total of 13 months. Sixteen of 51 such infants began excreting the virus at 28 to 148 days of age (mean, 55 days). In 14 of the 16, a recognizable, self-limited symptom complex developed that consisted of respiratory deterioration, hepatosplenomegaly, a remarkable gray pallor, and both an atypical and absolute lymphocytosis. All of the infants with the clinical symptom complex had underlying chronic lung disease and all had received multiple blood transfusions during their hospitalization. Acquired cytomegalovirus may be relatively common in sick preterm infants and should be distinguished from other causes of rapid deterioration.", "contents": "Acquired cytomegalovirus infection in preterm infants. Small sick preterm infants requiring care in a neonatal intensive care unit for more than 28 days were cultured for cytomegalovirus in urine and/or nasopharynx during two periods lasting a total of 13 months. Sixteen of 51 such infants began excreting the virus at 28 to 148 days of age (mean, 55 days). In 14 of the 16, a recognizable, self-limited symptom complex developed that consisted of respiratory deterioration, hepatosplenomegaly, a remarkable gray pallor, and both an atypical and absolute lymphocytosis. All of the infants with the clinical symptom complex had underlying chronic lung disease and all had received multiple blood transfusions during their hospitalization. Acquired cytomegalovirus may be relatively common in sick preterm infants and should be distinguished from other causes of rapid deterioration."}
{"id": "PMID:219686", "title": "Preoperative embolization of Wilms' tumors.", "content": "In two patients with Wilms' tumors, the ipsilateral kidney was nonfunctional. To facilitate initial surgical removal of the tumors, a preoperative transcatheter embolization was performed following diagnostic arteriography. Preoperative embolization of a renal tumor reduces the vascularity of the lesion prior to surgery, and a patient in whom primary surgical removal of the tumor would carry unacceptable risk may be converted into one in whom primary surgical removal is safe.", "contents": "Preoperative embolization of Wilms' tumors. In two patients with Wilms' tumors, the ipsilateral kidney was nonfunctional. To facilitate initial surgical removal of the tumors, a preoperative transcatheter embolization was performed following diagnostic arteriography. Preoperative embolization of a renal tumor reduces the vascularity of the lesion prior to surgery, and a patient in whom primary surgical removal of the tumor would carry unacceptable risk may be converted into one in whom primary surgical removal is safe."}
{"id": "PMID:219687", "title": "Hepatoma in a child with neurofibromatosis.", "content": "A 6-year-old girl had neurofibromatosis and hepatocellular carcinoma (hepatoma). Although neurofibromatosis is a common disorder, hepatic cancers are rare in childhood. Hepatic cancer, Wilms' tumor, and adrenocortical neoplasia are all seen with increased frequency in association with certain congenital anomalies, particularly with hemihypertrophy and various hamartomas. Neurofibromatosis, a hamartomatous disorder, is also seen with these congenital anomalies and it is reported with an unusually high incidence in patients with Wilms' tumor. We therefore suggest that these disorders may be related.", "contents": "Hepatoma in a child with neurofibromatosis. A 6-year-old girl had neurofibromatosis and hepatocellular carcinoma (hepatoma). Although neurofibromatosis is a common disorder, hepatic cancers are rare in childhood. Hepatic cancer, Wilms' tumor, and adrenocortical neoplasia are all seen with increased frequency in association with certain congenital anomalies, particularly with hemihypertrophy and various hamartomas. Neurofibromatosis, a hamartomatous disorder, is also seen with these congenital anomalies and it is reported with an unusually high incidence in patients with Wilms' tumor. We therefore suggest that these disorders may be related."}
{"id": "PMID:219688", "title": "Impact of swine influenza vaccine on serum antibody.", "content": "Comparison of a 1976 serum survey with one of 1977 has permitted an assessment of the impact of the national swine influenza vaccine program of 1976-1977 on the antibody status of the Michigan population. Prevalence of HI influenza virus antibody in premarital sera collected in 1976 prior to the vaccine program was compared to that in similar sera collected in 1977. Overall prevalence of A/New Jersey antibody (titers greater than or equal to 1:10) in 1976 sera was 22.3%. Little antibody was detected in sera from persons less than 40 years of age and prevalence peaked at age 50. Increased antibody prevalence was found for all age groups in sera collected in 1977 following the vaccine program, and the overall prevalence was 41.6%. Only 3.5% of those under 19 years of age were vaccinated, and post-vaccine prevalence for this group was 10%. This age group, comprising about 30% of the state population, appears to have had least exposure to swine influenza virus, and may be the population segment at greatest risk of infection should strains of this antigenic composition reappear. In contrast, highest prevalence of A/Victoria antibody was found in the 15 to 19 age group, where prevalence was 52%, compared to an overall prevalence at 40%.", "contents": "Impact of swine influenza vaccine on serum antibody. Comparison of a 1976 serum survey with one of 1977 has permitted an assessment of the impact of the national swine influenza vaccine program of 1976-1977 on the antibody status of the Michigan population. Prevalence of HI influenza virus antibody in premarital sera collected in 1976 prior to the vaccine program was compared to that in similar sera collected in 1977. Overall prevalence of A/New Jersey antibody (titers greater than or equal to 1:10) in 1976 sera was 22.3%. Little antibody was detected in sera from persons less than 40 years of age and prevalence peaked at age 50. Increased antibody prevalence was found for all age groups in sera collected in 1977 following the vaccine program, and the overall prevalence was 41.6%. Only 3.5% of those under 19 years of age were vaccinated, and post-vaccine prevalence for this group was 10%. This age group, comprising about 30% of the state population, appears to have had least exposure to swine influenza virus, and may be the population segment at greatest risk of infection should strains of this antigenic composition reappear. In contrast, highest prevalence of A/Victoria antibody was found in the 15 to 19 age group, where prevalence was 52%, compared to an overall prevalence at 40%."}
{"id": "PMID:219690", "title": "Small cell lung cancer. Complete remission and improved survival.", "content": "Thirty-two patients with limited-stage small cell lung cancer were treated with combined supervoltage radiotherapy and a combination of cyclophosphamide, doxorubicin and vincristine chemotherapy. The goal of obtaining a complete remission, the necessary step which precedes improved survival, was successful in 26 of 27 of completely re-evaluated patients. Fiberoptic bronchoscopy was useful in substantiating complete remission status. Seventeen of the 32 patients remain alive from 8+ to 28+ months (median 16+ months). Ten patients are alive and relapse-free from 12+ to 28+ months (median 19+ months). Transient granulocytopenia (mean nadir 650 cells/mm3) during induction therapy and the associated risk of infection were the most serious toxicities encountered. This therapy produces complete remission on roentgenography and bronchoscopy, symtomatic improvement and improved survival in the majority of patients with limited-stage small cell lung cancer. A portion of these patients may have their disease eradicated.", "contents": "Small cell lung cancer. Complete remission and improved survival. Thirty-two patients with limited-stage small cell lung cancer were treated with combined supervoltage radiotherapy and a combination of cyclophosphamide, doxorubicin and vincristine chemotherapy. The goal of obtaining a complete remission, the necessary step which precedes improved survival, was successful in 26 of 27 of completely re-evaluated patients. Fiberoptic bronchoscopy was useful in substantiating complete remission status. Seventeen of the 32 patients remain alive from 8+ to 28+ months (median 16+ months). Ten patients are alive and relapse-free from 12+ to 28+ months (median 19+ months). Transient granulocytopenia (mean nadir 650 cells/mm3) during induction therapy and the associated risk of infection were the most serious toxicities encountered. This therapy produces complete remission on roentgenography and bronchoscopy, symtomatic improvement and improved survival in the majority of patients with limited-stage small cell lung cancer. A portion of these patients may have their disease eradicated."}
{"id": "PMID:219691", "title": "Feedback-controlled dextrose infusion during surgical management of insulinomas.", "content": "Through the use of a feedback-controlled dextrose infusion system, we obtained continuous monitoring of the blood glucose level in a patient undergoing surgery for multiple pancreatic beta-cell tumors. In addition, this device infused dextrose at variable rates to maintain a predetermined euglycemic level of 90 mg/dl. Before locating the source of excessive insulin production, the maximum dextrose infusion rate of 400 mg/min was required; but after extirpation of multiple insulinomas, the dextrose-infusion rate declined whereas the blood glucose level rose above the preselected level. These results emphasize the usefulness of a monitoring and infusion system not only in protecting the patient from the hazard of hypoglycemia under anesthesia but also as an aid in determining whether all insulin-secreting tumors have been removed.", "contents": "Feedback-controlled dextrose infusion during surgical management of insulinomas. Through the use of a feedback-controlled dextrose infusion system, we obtained continuous monitoring of the blood glucose level in a patient undergoing surgery for multiple pancreatic beta-cell tumors. In addition, this device infused dextrose at variable rates to maintain a predetermined euglycemic level of 90 mg/dl. Before locating the source of excessive insulin production, the maximum dextrose infusion rate of 400 mg/min was required; but after extirpation of multiple insulinomas, the dextrose-infusion rate declined whereas the blood glucose level rose above the preselected level. These results emphasize the usefulness of a monitoring and infusion system not only in protecting the patient from the hazard of hypoglycemia under anesthesia but also as an aid in determining whether all insulin-secreting tumors have been removed."}
{"id": "PMID:219695", "title": "Hexamethylmelamine: an evaluation of its role in the treatment of ovarian cancer.", "content": "Hexamethylmelamine (HMM), NSC 13875, a synthetic agent structurally related to triethylenemelamine, has clinical antitumor activity and a role in the treatment of ovarian cancers of epithelial origin. Fifty-four patients, with International Federation of Gynecology and Obstetrics Stage III or IV carcinomas, previously untreated with chemotherapy or irradiation therapy, were treated with HMM (8 mg/kg/day) as a single agent at the M. D. Anderson Hospital and Tumor Institute in Houston, Texas, between January, 1973, and May, 1976. The response end points analyzed were complete plus partial response rate, duration of remission, and survival time. The complete and partial responses were verified whenever possible by \"second-look\" operation. Seventeen patients (31.8%) responded to HMM and three had no evidence of cancer, determined by multiple biopsies at second-look operation. Gastrointestinal, hematologic, and nervous system toxic effects were severe in 10 patients, requiring discontinuation of HMM. This study shows that HMM can induce a complete response and provide an extended disease-free interval without maintenance  chemotherapy.", "contents": "Hexamethylmelamine: an evaluation of its role in the treatment of ovarian cancer. Hexamethylmelamine (HMM), NSC 13875, a synthetic agent structurally related to triethylenemelamine, has clinical antitumor activity and a role in the treatment of ovarian cancers of epithelial origin. Fifty-four patients, with International Federation of Gynecology and Obstetrics Stage III or IV carcinomas, previously untreated with chemotherapy or irradiation therapy, were treated with HMM (8 mg/kg/day) as a single agent at the M. D. Anderson Hospital and Tumor Institute in Houston, Texas, between January, 1973, and May, 1976. The response end points analyzed were complete plus partial response rate, duration of remission, and survival time. The complete and partial responses were verified whenever possible by \"second-look\" operation. Seventeen patients (31.8%) responded to HMM and three had no evidence of cancer, determined by multiple biopsies at second-look operation. Gastrointestinal, hematologic, and nervous system toxic effects were severe in 10 patients, requiring discontinuation of HMM. This study shows that HMM can induce a complete response and provide an extended disease-free interval without maintenance  chemotherapy."}
{"id": "PMID:219696", "title": "Primary mucinous sweat gland carcinoma of the eyelid simulating metastatic carcinoma.", "content": "A 78-year-old man suffered an unusual variant of sweat gland carcinoma of the eyelid. This disorder is seldom recognized, and is frequently confused with inflammation, benign neoplasms, and metastatic carcinomas. On the basis of clinicopathologic and ultrastructural features found by both light and electron microscopy, we diagnosed sweat gland carcinoma of the eyelid. We considered the possibility of metastasis from a primary carcinoma elsewhere in the patient.", "contents": "Primary mucinous sweat gland carcinoma of the eyelid simulating metastatic carcinoma. A 78-year-old man suffered an unusual variant of sweat gland carcinoma of the eyelid. This disorder is seldom recognized, and is frequently confused with inflammation, benign neoplasms, and metastatic carcinomas. On the basis of clinicopathologic and ultrastructural features found by both light and electron microscopy, we diagnosed sweat gland carcinoma of the eyelid. We considered the possibility of metastasis from a primary carcinoma elsewhere in the patient."}
{"id": "PMID:219697", "title": "Multiple choroidal metastasis from bronchial carcinoid treated with photocoagulation and proton beam irradiation.", "content": "A 23-year-old man had bilateral multiple choroidal lesions eight years after removal of a bronchial carcinoid tumor. Choroidal biopsy confirmed that the clinical diagnosis and conventional radiotherapy to one eye resulted in rubeosis iridis, neovascular glaucoma, cataract, and vitreous hemorrhage. We were able to destroy the tumors in the other eye by photocoagulation and proton beam irradiation without any adverse effects. The patient is in good health 1 1/2 years after therapy and he has 6/6 (20/20) vision in the eye that was treated.", "contents": "Multiple choroidal metastasis from bronchial carcinoid treated with photocoagulation and proton beam irradiation. A 23-year-old man had bilateral multiple choroidal lesions eight years after removal of a bronchial carcinoid tumor. Choroidal biopsy confirmed that the clinical diagnosis and conventional radiotherapy to one eye resulted in rubeosis iridis, neovascular glaucoma, cataract, and vitreous hemorrhage. We were able to destroy the tumors in the other eye by photocoagulation and proton beam irradiation without any adverse effects. The patient is in good health 1 1/2 years after therapy and he has 6/6 (20/20) vision in the eye that was treated."}
{"id": "PMID:219698", "title": "Cellular toxicity of gentamicin.", "content": "Subconjunctival injections of gentamicin induced a lysosomal storage process within the conjunctival fibroblasts in rats, rabbits, and humans. Under electron microscopy, the accumulated substance was composed of a granular material and pleomorphic lamellar structures, corresponding to the presence of complex lipids. In animals, the other ocular tissues as well as the cells reached through the bloodstream remained unaffected, except the proximal convoluted tubules of the kidneys, where important lesions were evident. Although human kidneys were not examined in our study, we believe they might present similar alterations.", "contents": "Cellular toxicity of gentamicin. Subconjunctival injections of gentamicin induced a lysosomal storage process within the conjunctival fibroblasts in rats, rabbits, and humans. Under electron microscopy, the accumulated substance was composed of a granular material and pleomorphic lamellar structures, corresponding to the presence of complex lipids. In animals, the other ocular tissues as well as the cells reached through the bloodstream remained unaffected, except the proximal convoluted tubules of the kidneys, where important lesions were evident. Although human kidneys were not examined in our study, we believe they might present similar alterations."}
{"id": "PMID:219699", "title": "Monocyte and granulocyte defect in chronic lymphocytic leukemia.", "content": "Enzymatically homogeneous populations of lymphocytes, monocytes, and neutrophils were isolated by zonal centrifugation from 5 untreated patients with chronic lymphocytic leukemia (CLL) and 2 patients with CLL in full remission. The cells were then quantitatively analyzed for six leukocytic enzymes and compared with cells from normal subjects. CLL monocytes were deficient in beta-glucuronidase (0.06 units; normal, 0.16), myeloperoxidase (0.07 mg; normal, 0.5 mg), and lysozyme (0.7 mg; normal, 3.3 mg). In 2 cases, CLL neutrophils were severely deficient in lysozyme (1 to 2 mg; normal, 7 mg) and myeloperoxidase (2 to 3 mg; normal, 7 mg). Neutrophil alkaline phosphatase and neutral protease were unaffected. CLL lymphocytes shared with the monocytes the deficiency of beta-glucuronidase (0.03 units; normal, 0.09 units). The 2 CLL patients in full remission carried normal enzyme levels in leukocytes of all three cell lines. The CLL lymphocytes of untreated patients were unresponsive to mitogens but became responsive in remission. The CLL monocytes from both untreated and treated patients transformed into macrophages. The pattern of shared enzyme deficiency among lymphocytes, monocytes, and neutrophils of CLL patients and its normalization in all three cell types under remission suggest that the differentiation of the three leukocytic cell lines may be an enzymatically interlinked process and that the deficiency of these enzymes in leukemia may reflect an interrelated aberrant differentiation of the leukemic cells.", "contents": "Monocyte and granulocyte defect in chronic lymphocytic leukemia. Enzymatically homogeneous populations of lymphocytes, monocytes, and neutrophils were isolated by zonal centrifugation from 5 untreated patients with chronic lymphocytic leukemia (CLL) and 2 patients with CLL in full remission. The cells were then quantitatively analyzed for six leukocytic enzymes and compared with cells from normal subjects. CLL monocytes were deficient in beta-glucuronidase (0.06 units; normal, 0.16), myeloperoxidase (0.07 mg; normal, 0.5 mg), and lysozyme (0.7 mg; normal, 3.3 mg). In 2 cases, CLL neutrophils were severely deficient in lysozyme (1 to 2 mg; normal, 7 mg) and myeloperoxidase (2 to 3 mg; normal, 7 mg). Neutrophil alkaline phosphatase and neutral protease were unaffected. CLL lymphocytes shared with the monocytes the deficiency of beta-glucuronidase (0.03 units; normal, 0.09 units). The 2 CLL patients in full remission carried normal enzyme levels in leukocytes of all three cell lines. The CLL lymphocytes of untreated patients were unresponsive to mitogens but became responsive in remission. The CLL monocytes from both untreated and treated patients transformed into macrophages. The pattern of shared enzyme deficiency among lymphocytes, monocytes, and neutrophils of CLL patients and its normalization in all three cell types under remission suggest that the differentiation of the three leukocytic cell lines may be an enzymatically interlinked process and that the deficiency of these enzymes in leukemia may reflect an interrelated aberrant differentiation of the leukemic cells."}
{"id": "PMID:219700", "title": "Pathogenesis of reactivated latent murine cytomegalovirus infection.", "content": "Sixteen weeks after inoculation, murine cytomegalovirus (MCMV) can no longer be detected in the tissues of mice. However, a 2-week course of immunosuppression with antilymphocyte serum and cortisone acetate results in reactivation and dissemination of the latent virus in all animals. In this study of reactivation, MCMV was first detected in the liver, usually during the first week of immunosuppression, and virus replication was shown to be restricted to hepatocytes. Subsequently, a viremia occurred, with spread of infection to other organs. The highest titers of virus were reached in salivary glands in which replication occurred in serous acinar cells. In the lung, virus-specific abnormalities were difficult to detect because of superimposed bacterial and fungal infections. However, interstitial pneumonitis could be produced when cortisone acetate was deleted from the immunosuppressive regimen. Although the site of virus latency has not been defined, this model system will be useful for study of reactivation of latent cytomegalovirus infection.", "contents": "Pathogenesis of reactivated latent murine cytomegalovirus infection. Sixteen weeks after inoculation, murine cytomegalovirus (MCMV) can no longer be detected in the tissues of mice. However, a 2-week course of immunosuppression with antilymphocyte serum and cortisone acetate results in reactivation and dissemination of the latent virus in all animals. In this study of reactivation, MCMV was first detected in the liver, usually during the first week of immunosuppression, and virus replication was shown to be restricted to hepatocytes. Subsequently, a viremia occurred, with spread of infection to other organs. The highest titers of virus were reached in salivary glands in which replication occurred in serous acinar cells. In the lung, virus-specific abnormalities were difficult to detect because of superimposed bacterial and fungal infections. However, interstitial pneumonitis could be produced when cortisone acetate was deleted from the immunosuppressive regimen. Although the site of virus latency has not been defined, this model system will be useful for study of reactivation of latent cytomegalovirus infection."}
{"id": "PMID:219701", "title": "Superoxide production induced in rabbit polymorphonuclear leukocytes by synthetic chemotactic peptides and A23187.", "content": "SYNTHETIC FORMYL METHIONYL CHEMOTACTIC PEPTIDES INDUCE THE VARIOUS MANIFESTATIONS OFTHE RESPIRATORY BURST: increased 0(2) consumption, activation of the hexose mono-phosphate shunt, and increased production of superoxide (0(2) (-)) and H(2)0(2). They do soalone but to a much greater extent when in the presence of cytochalasin B. Superoxidegeneration by the chemotactic peptides in the presence of cytochalasin B shows thesame relationship of structure to activity as does the stimulation of chemokinesis andchemotaxis, granule enzyme secretion, and neutrophil aggregation by these sameagents. Carbobenzoxy-phenylalanyl-methionine, CBZ-Phe-Met, competitively inhibitsthe induced stimulation of locomotion, granule enzyme secretion, and neutrophilaggregation caused by the synthetic peptides. It also is a competitive inhibitor of O(2) (-) generation by the same peptides. The structure-activity and the competitive inhibitor studies lead to the conclusion that in polymorphonuclear leukocytes the chemotactic peptides induce superoxide formation and presumably the other manifestations of the respiratory burst by interacting with the same membrane receptor responsible for the stimulation of chemokinesis, chemotaxis, granule enzyme secretion, and neutrophil aggregation. The effectiveness of formyl-methionyl-leucyl-phenylalanine, F-Met-Leu-Phe, in generating 0(2) (-) is greatly reduced but not abolished by removing calcium from the external medium. The calcium ionophore A23187 induces 0(2) (-) generation that requires external calcium and is greatly enhanced by cytochalasin B. From these findings we hypothesize that the proximate cause of the induction of 0(2) (-) formation and other manifestations of the respiratory burst by the chemotactic peptides is the influx into the neutrophil of Ca(2+) and/or possibly Na(+) previously shown to be induced by the peptides.", "contents": "Superoxide production induced in rabbit polymorphonuclear leukocytes by synthetic chemotactic peptides and A23187. SYNTHETIC FORMYL METHIONYL CHEMOTACTIC PEPTIDES INDUCE THE VARIOUS MANIFESTATIONS OFTHE RESPIRATORY BURST: increased 0(2) consumption, activation of the hexose mono-phosphate shunt, and increased production of superoxide (0(2) (-)) and H(2)0(2). They do soalone but to a much greater extent when in the presence of cytochalasin B. Superoxidegeneration by the chemotactic peptides in the presence of cytochalasin B shows thesame relationship of structure to activity as does the stimulation of chemokinesis andchemotaxis, granule enzyme secretion, and neutrophil aggregation by these sameagents. Carbobenzoxy-phenylalanyl-methionine, CBZ-Phe-Met, competitively inhibitsthe induced stimulation of locomotion, granule enzyme secretion, and neutrophilaggregation caused by the synthetic peptides. It also is a competitive inhibitor of O(2) (-) generation by the same peptides. The structure-activity and the competitive inhibitor studies lead to the conclusion that in polymorphonuclear leukocytes the chemotactic peptides induce superoxide formation and presumably the other manifestations of the respiratory burst by interacting with the same membrane receptor responsible for the stimulation of chemokinesis, chemotaxis, granule enzyme secretion, and neutrophil aggregation. The effectiveness of formyl-methionyl-leucyl-phenylalanine, F-Met-Leu-Phe, in generating 0(2) (-) is greatly reduced but not abolished by removing calcium from the external medium. The calcium ionophore A23187 induces 0(2) (-) generation that requires external calcium and is greatly enhanced by cytochalasin B. From these findings we hypothesize that the proximate cause of the induction of 0(2) (-) formation and other manifestations of the respiratory burst by the chemotactic peptides is the influx into the neutrophil of Ca(2+) and/or possibly Na(+) previously shown to be induced by the peptides."}
{"id": "PMID:219702", "title": "Effects of thyroid deficiency and sympathectomy on cardiac enzymes.", "content": "The effects of thyroid deficiency (Td) and of chemical sympathectomy (Sx) were studied on marker enzymes of energy metabolism in cardiac muscle of neonatal and of adult rats. Td prevented the normal development of neonatal body weight, relative heart mass, and cardiac levels of cytochrome c (-22%), citrate synthase (-27%), phosphofructokinase (-20%) and Mg2+- and Ca2+-ATPase activity of purified myofibrils (-33%, -44%). Exogenous thyroxin replacement restored those parameters studied to normal with the exception that it persistently elevated citrate synthase activity significantly above normal control levels. Responses similar to those of Td neonates occurred when adult rats were similarly treated. Sx produced no consistent effects on respiratory and glycogenolytic marker enzymes, but caused a 20% reduction in Ca2+-ATPase activity of both neonatal and adult cardiac myofibrils. These findings suggest that cardiac muscle cells require thyroxin for normal growth and enzyme development. Also, Sx may impair cardiac functional capacity by altering Ca2+ activity of actomyosin ATPase.", "contents": "Effects of thyroid deficiency and sympathectomy on cardiac enzymes. The effects of thyroid deficiency (Td) and of chemical sympathectomy (Sx) were studied on marker enzymes of energy metabolism in cardiac muscle of neonatal and of adult rats. Td prevented the normal development of neonatal body weight, relative heart mass, and cardiac levels of cytochrome c (-22%), citrate synthase (-27%), phosphofructokinase (-20%) and Mg2+- and Ca2+-ATPase activity of purified myofibrils (-33%, -44%). Exogenous thyroxin replacement restored those parameters studied to normal with the exception that it persistently elevated citrate synthase activity significantly above normal control levels. Responses similar to those of Td neonates occurred when adult rats were similarly treated. Sx produced no consistent effects on respiratory and glycogenolytic marker enzymes, but caused a 20% reduction in Ca2+-ATPase activity of both neonatal and adult cardiac myofibrils. These findings suggest that cardiac muscle cells require thyroxin for normal growth and enzyme development. Also, Sx may impair cardiac functional capacity by altering Ca2+ activity of actomyosin ATPase."}
{"id": "PMID:219703", "title": "Myasthenia in frogs immunized against cholinergic-receptor protein.", "content": "Frogs immunized with cholinergic-receptor protein developed myasthenia in 116--175 days. The muscular weakness was overcome by subcutaneous administration of 20 microgram of neostigmine. Electromyograms showed a decline in action potential amplitude during a 2-Hz train. Nerve stimulation evoked subthreshold end-plate potentials (EPPs) averaging 10.4 +/- 7.4 mV, but at many junctions no EPP was obtained. Miniature EPP amplitude had a modal value of 0.15 mV compared with 0.35 mV for the controls. The corresponding means were 0.24 +/- 0.23 mV and 0.48 +/- 0.23 mV. Microperfusion with edrophonium (5 mg/l) increased the amplitude of EPPs and miniature end-plate potentials (MEPPS). Postjunctional response tested with 20 muM carbamylcholine was 56% of control. Postjunctional response by carbamylcholine iontophoresis gave 19 +/- 22 mV/nC compared with 76 +/- 50 mV/nC for the controls. The data indicate that the neuromuscular transmission deficits in receptor-immunized frogs are mainly postsynaptic in origin, but there may be additional presynaptic contributions. This amphibian model of myasthenia gravis offers many opportunities and advantages in the study of receptor-immunized animals.", "contents": "Myasthenia in frogs immunized against cholinergic-receptor protein. Frogs immunized with cholinergic-receptor protein developed myasthenia in 116--175 days. The muscular weakness was overcome by subcutaneous administration of 20 microgram of neostigmine. Electromyograms showed a decline in action potential amplitude during a 2-Hz train. Nerve stimulation evoked subthreshold end-plate potentials (EPPs) averaging 10.4 +/- 7.4 mV, but at many junctions no EPP was obtained. Miniature EPP amplitude had a modal value of 0.15 mV compared with 0.35 mV for the controls. The corresponding means were 0.24 +/- 0.23 mV and 0.48 +/- 0.23 mV. Microperfusion with edrophonium (5 mg/l) increased the amplitude of EPPs and miniature end-plate potentials (MEPPS). Postjunctional response tested with 20 muM carbamylcholine was 56% of control. Postjunctional response by carbamylcholine iontophoresis gave 19 +/- 22 mV/nC compared with 76 +/- 50 mV/nC for the controls. The data indicate that the neuromuscular transmission deficits in receptor-immunized frogs are mainly postsynaptic in origin, but there may be additional presynaptic contributions. This amphibian model of myasthenia gravis offers many opportunities and advantages in the study of receptor-immunized animals."}
{"id": "PMID:219704", "title": "Effect of tolbutamide on plasma renin activity.", "content": "The effect of tolbutamide on renin secretion in rats was studied in vivo, and in vitro. Administration of tolbutamide in doses of 12.5 and 25 mg/kg body wt ip to two groups of rats produced no significant change in plasma renin activity compared to the control group. In the in vitro experiments renal cortical slices were incubated with increasing concentrations of tolbutamide (0--4 mg/ml). No significant increase in the net renin production was observed, whereas the concentration of cyclic AMP increased significantly in the incubation medium. These findings suggest that in the intact rats tolbutamide does not increase plasma renin activity. In the renal cortical experiments although tolbutamide increased cyclic AMP production, the increase may not have been sufficient to stimulate the net renin production. These results are of biological significance because of the possible effects of tolbutamide and increased plasma renin activity on the cardiovascular system.", "contents": "Effect of tolbutamide on plasma renin activity. The effect of tolbutamide on renin secretion in rats was studied in vivo, and in vitro. Administration of tolbutamide in doses of 12.5 and 25 mg/kg body wt ip to two groups of rats produced no significant change in plasma renin activity compared to the control group. In the in vitro experiments renal cortical slices were incubated with increasing concentrations of tolbutamide (0--4 mg/ml). No significant increase in the net renin production was observed, whereas the concentration of cyclic AMP increased significantly in the incubation medium. These findings suggest that in the intact rats tolbutamide does not increase plasma renin activity. In the renal cortical experiments although tolbutamide increased cyclic AMP production, the increase may not have been sufficient to stimulate the net renin production. These results are of biological significance because of the possible effects of tolbutamide and increased plasma renin activity on the cardiovascular system."}
{"id": "PMID:219705", "title": "Sodium-coupled chloride transport by epithelial tissues.", "content": "There is compelling evidence that active Cl absorption by a variety of epithelia, widely distributed throughout the animal kingdom, is the result of an electrically neutral Na-coupled transport process at the luminal membrane and that the energy for transcellular Cl movement is derived from the Na gradient across that barrier. These co-transport processes are found predominantly in \"leaky\" or \"moderately leaky\" epithelia and permit these tissues to absorb Na and Cl with high degrees of efficacy. In addition, there is a growing body of evidence that cyclic AMP and Ca-induced electrogenic Cl secretion by a wide variety of epithelia may involve electrically neutral, Na-coupled Cl entry across the contraluminal membrane and that the energy for these secretory processes is derived from the Na-gradient across that barrier. A model for electrogenic Cl secretion that accounts for the available data is presented.", "contents": "Sodium-coupled chloride transport by epithelial tissues. There is compelling evidence that active Cl absorption by a variety of epithelia, widely distributed throughout the animal kingdom, is the result of an electrically neutral Na-coupled transport process at the luminal membrane and that the energy for transcellular Cl movement is derived from the Na gradient across that barrier. These co-transport processes are found predominantly in \"leaky\" or \"moderately leaky\" epithelia and permit these tissues to absorb Na and Cl with high degrees of efficacy. In addition, there is a growing body of evidence that cyclic AMP and Ca-induced electrogenic Cl secretion by a wide variety of epithelia may involve electrically neutral, Na-coupled Cl entry across the contraluminal membrane and that the energy for these secretory processes is derived from the Na-gradient across that barrier. A model for electrogenic Cl secretion that accounts for the available data is presented."}
{"id": "PMID:219708", "title": "Time course of the renal response to triiodothyronine in the rat.", "content": "Experiments were carried out to compare temporal changes in glomerular filtration rate (GFR), filtered Na+ load, and renal cortical (Na+ + K+)-adenosine triphosphatase (Na-K-ATPase) activity in the hypothyroid rat after administration of a single dose of triiodothyronine (T3) (50 microgram/100 g body wt). The cortex showed an increase in Na-K-ATPase at 24 h and progressive increases to a peak of 62% at 48 h. GFR and filtered Na+ load showed no changes at 24 and 48 h. At 72h, however, significant increases of 62 and 63% (per rat) were observed in GFR and filtered Na+ load, respectively. The results show that the early increase in Na-K-ATPase activity upon T3 treatment precedes the increases in GFR and filtered Na+ load, suggesting a direct effect of T3 on the regulation of Na-K-ATPase activity in the hypothyroid rat kidney cortex, rather than a secondary response to a primary increase in filtered Na+ load as proposed previously.", "contents": "Time course of the renal response to triiodothyronine in the rat. Experiments were carried out to compare temporal changes in glomerular filtration rate (GFR), filtered Na+ load, and renal cortical (Na+ + K+)-adenosine triphosphatase (Na-K-ATPase) activity in the hypothyroid rat after administration of a single dose of triiodothyronine (T3) (50 microgram/100 g body wt). The cortex showed an increase in Na-K-ATPase at 24 h and progressive increases to a peak of 62% at 48 h. GFR and filtered Na+ load showed no changes at 24 and 48 h. At 72h, however, significant increases of 62 and 63% (per rat) were observed in GFR and filtered Na+ load, respectively. The results show that the early increase in Na-K-ATPase activity upon T3 treatment precedes the increases in GFR and filtered Na+ load, suggesting a direct effect of T3 on the regulation of Na-K-ATPase activity in the hypothyroid rat kidney cortex, rather than a secondary response to a primary increase in filtered Na+ load as proposed previously."}
{"id": "PMID:219709", "title": "Development of angiotensin-converting enzyme in fetal rat lungs.", "content": "Angiotensin-converting enzyme (ACE) catalyzes rapid hydrolytic cleavage of angiotensin I to form angiotensin II (AII). Inasmuch as converting enzyme activity is present at birth and increases postnatally to adult values it was of interest to determine the prenatal development of ACE. Converting enzyme activity was determined in the 20,000 x g supernatant fraction of lung homogenates using hippuryl-L-histidyl-L-leucine (HHL) as substrate. Hippuric acid liberated by the hydrolysis of HHL was quantified spectrophotometrically. ACE activity was first detectable at 18 days of gestation and increased fourfold prior to birth (21 days gestation). Pulmonary ACE activity of 1-day-old animals was twice that of fetuses at day 20 of gestation; however, this increase did not appear to result from ventilation alone. The Michaelis-Menten constant for fetal ACE (2.0 mM HHL) was not different from that calculated for ACE of adult rat lungs (2.6 mM). These data were interpreted to indicate that the age-related increase in ACE activity was due to greater ACE content as opposed to further activation of preexisting enzyme. This increase in fetal ACE activity may play an important role in preparing the renin-angiotensin system for postnatal function.", "contents": "Development of angiotensin-converting enzyme in fetal rat lungs. Angiotensin-converting enzyme (ACE) catalyzes rapid hydrolytic cleavage of angiotensin I to form angiotensin II (AII). Inasmuch as converting enzyme activity is present at birth and increases postnatally to adult values it was of interest to determine the prenatal development of ACE. Converting enzyme activity was determined in the 20,000 x g supernatant fraction of lung homogenates using hippuryl-L-histidyl-L-leucine (HHL) as substrate. Hippuric acid liberated by the hydrolysis of HHL was quantified spectrophotometrically. ACE activity was first detectable at 18 days of gestation and increased fourfold prior to birth (21 days gestation). Pulmonary ACE activity of 1-day-old animals was twice that of fetuses at day 20 of gestation; however, this increase did not appear to result from ventilation alone. The Michaelis-Menten constant for fetal ACE (2.0 mM HHL) was not different from that calculated for ACE of adult rat lungs (2.6 mM). These data were interpreted to indicate that the age-related increase in ACE activity was due to greater ACE content as opposed to further activation of preexisting enzyme. This increase in fetal ACE activity may play an important role in preparing the renin-angiotensin system for postnatal function."}
{"id": "PMID:219710", "title": "alpha-Sympathetic control of glucose output of mouse liver perfused in situ.", "content": "Electrical stimulation of perivascular nerve bundles of mouse liver perfused in situ at constant flow resulted in an increase of glucose production that was maximal at 20 Hz. The neurally induced glucose output was inhibited significantly by the beta-blocker propranolol, and to a considerably greater extent by the alpha-blockers, phenoxybenzamine and phentolamine. The effect of 20-Hz electrical stimulation could be matched by an infusion of norepinephrine at a concentration of 5 X 10(-7) M. It is suggested that the carbohydrate metabolism of the liver is controlled by its own nerve supply rather than by circulating catecholamines and that alpha-adrenergic receptors have a greater effect than beta-receptors on hepatic glucose production resulting from electrical and catecholamine stimulation.", "contents": "alpha-Sympathetic control of glucose output of mouse liver perfused in situ. Electrical stimulation of perivascular nerve bundles of mouse liver perfused in situ at constant flow resulted in an increase of glucose production that was maximal at 20 Hz. The neurally induced glucose output was inhibited significantly by the beta-blocker propranolol, and to a considerably greater extent by the alpha-blockers, phenoxybenzamine and phentolamine. The effect of 20-Hz electrical stimulation could be matched by an infusion of norepinephrine at a concentration of 5 X 10(-7) M. It is suggested that the carbohydrate metabolism of the liver is controlled by its own nerve supply rather than by circulating catecholamines and that alpha-adrenergic receptors have a greater effect than beta-receptors on hepatic glucose production resulting from electrical and catecholamine stimulation."}
{"id": "PMID:219711", "title": "Effects on rat parotid amylase and Ca of alpha- and beta-adrenergic sympathetic stimulation.", "content": "The roles of alpha- and beta-adrenergic receptors in the regulation of the secretion of amylase and calcium from rat parotid gland were studied by using direct electrical stimulation of the sympathetic innervation to the gland in the presence of selective adrenergic blocking agents. When phenoxybenzamine was administered intraperitoneally 25 min prior to nerve stimulation, the highest [Ca] (12-14 meq/liter) and amylase activity (1,000 mg/microliter) in the evoked saliva were observed. On the other hand, stimulation of the nerve in the presence of propranolol evoked a saliva that contained the lowest [Ca] (5-6 meq/liter) and amylase activity (170 mg/microliter). Furthermore, salivary flow (4.27 +/- 0.42 microliter/min X g) induced by sympathetic nerve stimulation in the presence of phenoxybenzamine was higher than that induced by sympathetic nerve stimulation in the presence of propranolol (2.55 +/- 0.39 microliter/min X g). Therefore, it was concluded that beta-adrenergic receptors play the major role in the regulation of salivary flow and the secretion of amylase and calcium, whereas alpha-adrenergic receptors play a minor role in the regulation of these parameters.", "contents": "Effects on rat parotid amylase and Ca of alpha- and beta-adrenergic sympathetic stimulation. The roles of alpha- and beta-adrenergic receptors in the regulation of the secretion of amylase and calcium from rat parotid gland were studied by using direct electrical stimulation of the sympathetic innervation to the gland in the presence of selective adrenergic blocking agents. When phenoxybenzamine was administered intraperitoneally 25 min prior to nerve stimulation, the highest [Ca] (12-14 meq/liter) and amylase activity (1,000 mg/microliter) in the evoked saliva were observed. On the other hand, stimulation of the nerve in the presence of propranolol evoked a saliva that contained the lowest [Ca] (5-6 meq/liter) and amylase activity (170 mg/microliter). Furthermore, salivary flow (4.27 +/- 0.42 microliter/min X g) induced by sympathetic nerve stimulation in the presence of phenoxybenzamine was higher than that induced by sympathetic nerve stimulation in the presence of propranolol (2.55 +/- 0.39 microliter/min X g). Therefore, it was concluded that beta-adrenergic receptors play the major role in the regulation of salivary flow and the secretion of amylase and calcium, whereas alpha-adrenergic receptors play a minor role in the regulation of these parameters."}
{"id": "PMID:219714", "title": "Cation-anion gap and choleretic properties of rat bile.", "content": "To investigate whether bile contains choleretic anion(s) other than bile salts (BS) that could account for the observed cation-anion gap in bile, the choleretic properties of bile were investigated in the rat. Infusion of bile increased bile flow significantly more than did taurocholate (TC) (P less than 0.005). By contrast, TC increased BS excretion more substantially (P less than 0.01). This effect was dose dependent for both bile and TC. The choleretic principle had a molecular weight of less than 1,000 as estimated by ultrafiltration of bile. Infusion of bile that had been chromatographed on BioBeads SM-2 still elicited choleresis, whereas bile that had been chromatographed on Dowex 1 x 50W did not. Administration of bile in vivo did not affect Na+-K+-stimulated ATPase activity in liver plasma membrane fractions. These results suggest that bile contains anion(s) other than 3-hydroxy-BS, which increase bile flow in a dose-dependent fashion without affecting the permeability of the biliary tree. This putative choleretic appears to be anionic in nature, heat stable, and has an apparent molecular weight of less than 1,000. This finding suggested that bile salt-independent bile flow partly depends on the excretion of a currently undefined anion.", "contents": "Cation-anion gap and choleretic properties of rat bile. To investigate whether bile contains choleretic anion(s) other than bile salts (BS) that could account for the observed cation-anion gap in bile, the choleretic properties of bile were investigated in the rat. Infusion of bile increased bile flow significantly more than did taurocholate (TC) (P less than 0.005). By contrast, TC increased BS excretion more substantially (P less than 0.01). This effect was dose dependent for both bile and TC. The choleretic principle had a molecular weight of less than 1,000 as estimated by ultrafiltration of bile. Infusion of bile that had been chromatographed on BioBeads SM-2 still elicited choleresis, whereas bile that had been chromatographed on Dowex 1 x 50W did not. Administration of bile in vivo did not affect Na+-K+-stimulated ATPase activity in liver plasma membrane fractions. These results suggest that bile contains anion(s) other than 3-hydroxy-BS, which increase bile flow in a dose-dependent fashion without affecting the permeability of the biliary tree. This putative choleretic appears to be anionic in nature, heat stable, and has an apparent molecular weight of less than 1,000. This finding suggested that bile salt-independent bile flow partly depends on the excretion of a currently undefined anion."}
{"id": "PMID:219715", "title": "Development of secretory mechanisms in rat pancreas.", "content": "Mechanisms and development of secretory function were studied in rat pancreas in vitro. Amylase release from term fetal pancreas was refractory to stimulation by carbamylcholine chloride (carbachol) and cholecystokinin-octapeptide (CCK-OP), but was significantly augmented by calcium ionophore (A23187), DBcAMP, 8-Br-cGMP, and theophylline. The latter agent when combined with either cyclic nucleotide analogue further increased secretory responses. At 1 day and 8 days postnatally, responsiveness to carbachol and CCK-OP had been acquired because amylase secretion stimulated by these agents was brisk and at a level comparable to that found in mature tissue. Increasing extracellular calcium concentrations from 1.23 to 5.28 mM had no effect on basal amylase release in either the fetal or 8-day pancreas. No changes in intracellular cAMP concentrations were found at any age under experimental conditions used. Similarily, in fetal tissue, no changes in cGMP concentrations were found in response to carbachol or A23187. However, at 8 days of age, both agents produced two- to four-fold increases in tissue cGMP levels at 1, 2, and 5 min of incubation. These studies confirm that responsiveness to carbachol and CCK-OP is a maturational process in the pancreas that lags behind the development of intracellular processes involved in stimulus-secretion coupling.", "contents": "Development of secretory mechanisms in rat pancreas. Mechanisms and development of secretory function were studied in rat pancreas in vitro. Amylase release from term fetal pancreas was refractory to stimulation by carbamylcholine chloride (carbachol) and cholecystokinin-octapeptide (CCK-OP), but was significantly augmented by calcium ionophore (A23187), DBcAMP, 8-Br-cGMP, and theophylline. The latter agent when combined with either cyclic nucleotide analogue further increased secretory responses. At 1 day and 8 days postnatally, responsiveness to carbachol and CCK-OP had been acquired because amylase secretion stimulated by these agents was brisk and at a level comparable to that found in mature tissue. Increasing extracellular calcium concentrations from 1.23 to 5.28 mM had no effect on basal amylase release in either the fetal or 8-day pancreas. No changes in intracellular cAMP concentrations were found at any age under experimental conditions used. Similarily, in fetal tissue, no changes in cGMP concentrations were found in response to carbachol or A23187. However, at 8 days of age, both agents produced two- to four-fold increases in tissue cGMP levels at 1, 2, and 5 min of incubation. These studies confirm that responsiveness to carbachol and CCK-OP is a maturational process in the pancreas that lags behind the development of intracellular processes involved in stimulus-secretion coupling."}
{"id": "PMID:219716", "title": "Effect of altered intestinal water transport on rabbit ileal blood flow.", "content": "A method is described for measuring ileal blood flow in the anesthetized (pentobarbital sodium) rabbit by the intraventricular injection of microspheres (15 micrometer) labeled with cerium-141 or chromium-51; with this method the amount of labeled microspheres lodging in the tissue is proportional to the blood flow. Blood flow to the ileal mucosa plus submucosa could be separated from flow to the ileal muscularis propria plus serosa by this technique. Simultaneous and sequential injections of radiolabeled microspheres gave similar measurements of ileal blood flow and did not affect ileal water absorption. Increasing ileal water absorption by treatment with the glucocorticoid methylprednisolone (3 mg/100 g per day for 3 days) increased blood flow to both compartments of the ileum and also to the colon, liver, and kidneys; methylprednisolone treatment did not alter blood flow when studies were performed before the methylprednisolone-induced increase in ileal water absorption had occurred. In contrast, intestinal secretagogues that induced both active ileal secretion (purified cholera toxin and serotonin) and passive ileal secretion (hypertonic mannitol) did not affect ileal blood flow. These studies indicate that increased ileal water absorption is associated with increased ileal blood flow, whereas intestinal secretion is not necessarily associated with an alteration in ileal blood flow.", "contents": "Effect of altered intestinal water transport on rabbit ileal blood flow. A method is described for measuring ileal blood flow in the anesthetized (pentobarbital sodium) rabbit by the intraventricular injection of microspheres (15 micrometer) labeled with cerium-141 or chromium-51; with this method the amount of labeled microspheres lodging in the tissue is proportional to the blood flow. Blood flow to the ileal mucosa plus submucosa could be separated from flow to the ileal muscularis propria plus serosa by this technique. Simultaneous and sequential injections of radiolabeled microspheres gave similar measurements of ileal blood flow and did not affect ileal water absorption. Increasing ileal water absorption by treatment with the glucocorticoid methylprednisolone (3 mg/100 g per day for 3 days) increased blood flow to both compartments of the ileum and also to the colon, liver, and kidneys; methylprednisolone treatment did not alter blood flow when studies were performed before the methylprednisolone-induced increase in ileal water absorption had occurred. In contrast, intestinal secretagogues that induced both active ileal secretion (purified cholera toxin and serotonin) and passive ileal secretion (hypertonic mannitol) did not affect ileal blood flow. These studies indicate that increased ileal water absorption is associated with increased ileal blood flow, whereas intestinal secretion is not necessarily associated with an alteration in ileal blood flow."}
{"id": "PMID:219717", "title": "Involvement of renal alpha- and beta-adrenoceptors in release of renin by carotid baroreflex.", "content": "In anesthetized vagotomized dogs with renal arterial pressure constant, carotid sinus hypotension (BCO) caused a reflex rise in systemic arterial pressure, a fall in renal blood flow, and a similar increase in renin release from both kidneys. Unilateral alpha-adrenoceptor blockade with phenoxybenzamine resulted in an increase in basal renal blood flow, a depression of basal renin release, and an abolition of the responses to BCO in the treated kidney. The untreated kidney responsed to BCO as before. Nonblocked and alpha-blocked kidneys released similar amounts of renin when renal blood flow was mechanically reduced by aortic constriction. Administration of propranolol to the nonblocked kidney prevented the release of renin but not the hemodynamic changes resulting from BCO. The experiments demonstrated that under certain conditions carotid sinus hypotension produced alpha-adrenoceptor-mediated changes in the kidney sufficient to cause increased renin release. A step in the renin release mechanism subsequent to the alpha-adrenoceptor-mediated changes in sensitive to propranolol.", "contents": "Involvement of renal alpha- and beta-adrenoceptors in release of renin by carotid baroreflex. In anesthetized vagotomized dogs with renal arterial pressure constant, carotid sinus hypotension (BCO) caused a reflex rise in systemic arterial pressure, a fall in renal blood flow, and a similar increase in renin release from both kidneys. Unilateral alpha-adrenoceptor blockade with phenoxybenzamine resulted in an increase in basal renal blood flow, a depression of basal renin release, and an abolition of the responses to BCO in the treated kidney. The untreated kidney responsed to BCO as before. Nonblocked and alpha-blocked kidneys released similar amounts of renin when renal blood flow was mechanically reduced by aortic constriction. Administration of propranolol to the nonblocked kidney prevented the release of renin but not the hemodynamic changes resulting from BCO. The experiments demonstrated that under certain conditions carotid sinus hypotension produced alpha-adrenoceptor-mediated changes in the kidney sufficient to cause increased renin release. A step in the renin release mechanism subsequent to the alpha-adrenoceptor-mediated changes in sensitive to propranolol."}
{"id": "PMID:219718", "title": "Research on the psychosocial treatment of schizophrenia: a summary report.", "content": "The authors present an overview of research on psychosocial treatments for schizophrenia. Findings from studies of five therapeutic approaches--individual psychotherapy, group psychotherapy, family therapy, milieu therapy, and community support systems--are discussed in detail. The usefulness of each type of therapy is critically assessed on the basis of available data from controlled outcome studies. The authors make recommendations regarding high-priority areas to be addressed in future studies of psychosocial treatment.", "contents": "Research on the psychosocial treatment of schizophrenia: a summary report. The authors present an overview of research on psychosocial treatments for schizophrenia. Findings from studies of five therapeutic approaches--individual psychotherapy, group psychotherapy, family therapy, milieu therapy, and community support systems--are discussed in detail. The usefulness of each type of therapy is critically assessed on the basis of available data from controlled outcome studies. The authors make recommendations regarding high-priority areas to be addressed in future studies of psychosocial treatment."}
{"id": "PMID:219719", "title": "Beta-adrenergic receptor function in affective illness.", "content": "In a study of beta-adrenergic receptor sensitivity, the authors determined the response of cyclic AMP synthesis to in vitro addition of norepinephrine (NE) and isoproterenol (IP) in leukocytes of patients with affective illness and schizophrenia and of normal controls. IP-stimulated increase in 3H-cyclic AMP synthesis in depressed patients was significantly lower than in normal subjects and schizophrenic patients. These results suggest that beta-adrenergic receptor sensitivity is reduced in depressive illness.", "contents": "Beta-adrenergic receptor function in affective illness. In a study of beta-adrenergic receptor sensitivity, the authors determined the response of cyclic AMP synthesis to in vitro addition of norepinephrine (NE) and isoproterenol (IP) in leukocytes of patients with affective illness and schizophrenia and of normal controls. IP-stimulated increase in 3H-cyclic AMP synthesis in depressed patients was significantly lower than in normal subjects and schizophrenic patients. These results suggest that beta-adrenergic receptor sensitivity is reduced in depressive illness."}
{"id": "PMID:219720", "title": "Reduced cyclic AMP production in the blood platelets from schizophrenic patients.", "content": "The authors assessed alpha-adrenergic receptor function in blood platelets from chronic schizophrenic patients and normal control subjects. The number of receptors was measured by the specific binding of the alpha-adrenergic antagonist [3H]dihydroergocryptine to the platelets. A physiological response of the platelets to agonist occupancy of the alpha-adrenergic receptors was measured by the norepinephrine inhibition of prostaglandin E1(PGE1)-stimulated cyclic AMP (cAMP) production. cAMP production in male schizophrenic patients was lower than in normal male subjects. alpha-Adrenergic receptor function was similar in patients and normal control subjects of both sexes. Normal male subjects had about 1.5 times the number of alpha-adrenergic receptors as normal females and generated about 1.8 times the quantity of PGE1-stimulated cAMP.", "contents": "Reduced cyclic AMP production in the blood platelets from schizophrenic patients. The authors assessed alpha-adrenergic receptor function in blood platelets from chronic schizophrenic patients and normal control subjects. The number of receptors was measured by the specific binding of the alpha-adrenergic antagonist [3H]dihydroergocryptine to the platelets. A physiological response of the platelets to agonist occupancy of the alpha-adrenergic receptors was measured by the norepinephrine inhibition of prostaglandin E1(PGE1)-stimulated cyclic AMP (cAMP) production. cAMP production in male schizophrenic patients was lower than in normal male subjects. alpha-Adrenergic receptor function was similar in patients and normal control subjects of both sexes. Normal male subjects had about 1.5 times the number of alpha-adrenergic receptors as normal females and generated about 1.8 times the quantity of PGE1-stimulated cAMP."}
{"id": "PMID:219722", "title": "Japanese encephalitis virus in mosquito salivary glands.", "content": "Culex tritaeniorhynchus and C. pipiens mosquitoes were infected with Japanese encephalitis virus either by intrathoracic injection or by membrane feeding. The virus maturation sites and the process of virus particle concentration in salivary gland cells were studied by electron microscopy. Occurrence of mature virions was primarily associated with intracytoplasmic viral matrices which were extraordinarily large and had a perinuclear location in C. pipiens mosquitoes. The other sign of virus replication was the proliferation of small spherical vesicles throughout the cytoplasm. It appeared that mature virions were entrapped in intracellular vacuoles and later released into the apical cavity of salivary gland cells through the fusion of these vacuoles with the apical plasma membrane. This process seemed to be associated with primary resynthesis of saliva in mosquitoes following blood feeding activity. Another type of shedding involved virus particles either singly or in mass being released directly through the apical plasma membrane. All of these events occurred only in cells of the lateral lobes of the salivary glands, which fact was confirmed by immunofluorescent staining of infected glands. The median lobe of mosquito salivary glands may have a minor or no role in the transmission of Japanese encephalitis virus.", "contents": "Japanese encephalitis virus in mosquito salivary glands. Culex tritaeniorhynchus and C. pipiens mosquitoes were infected with Japanese encephalitis virus either by intrathoracic injection or by membrane feeding. The virus maturation sites and the process of virus particle concentration in salivary gland cells were studied by electron microscopy. Occurrence of mature virions was primarily associated with intracytoplasmic viral matrices which were extraordinarily large and had a perinuclear location in C. pipiens mosquitoes. The other sign of virus replication was the proliferation of small spherical vesicles throughout the cytoplasm. It appeared that mature virions were entrapped in intracellular vacuoles and later released into the apical cavity of salivary gland cells through the fusion of these vacuoles with the apical plasma membrane. This process seemed to be associated with primary resynthesis of saliva in mosquitoes following blood feeding activity. Another type of shedding involved virus particles either singly or in mass being released directly through the apical plasma membrane. All of these events occurred only in cells of the lateral lobes of the salivary glands, which fact was confirmed by immunofluorescent staining of infected glands. The median lobe of mosquito salivary glands may have a minor or no role in the transmission of Japanese encephalitis virus."}
{"id": "PMID:219723", "title": "Clinical and laboratory features and treatment of visceral leishmaniasis in hospitalized patients in Northwestern Ethiopia.", "content": "The clinical and laboratory features, and the response to treatment of visceral leishmaniasis were studied in 18 hospitalized patients. Clinical and laboratory findings were similar to those in patients with kala-azar in the Sudan and East Africa. Fever, heptosplenomegaly, relative lymphocytosis, leukopenia, low platelet counts, and severe anemia were common findings. Pentostam (sodium stibogluconate) was used to treat 17 patients and Neostibosam (ethylstibamine) for one. Three patients died. Four out of the 18 patients had not visited any known endemic area but the significance of this finding has not been fully evaluated.", "contents": "Clinical and laboratory features and treatment of visceral leishmaniasis in hospitalized patients in Northwestern Ethiopia. The clinical and laboratory features, and the response to treatment of visceral leishmaniasis were studied in 18 hospitalized patients. Clinical and laboratory findings were similar to those in patients with kala-azar in the Sudan and East Africa. Fever, heptosplenomegaly, relative lymphocytosis, leukopenia, low platelet counts, and severe anemia were common findings. Pentostam (sodium stibogluconate) was used to treat 17 patients and Neostibosam (ethylstibamine) for one. Three patients died. Four out of the 18 patients had not visited any known endemic area but the significance of this finding has not been fully evaluated."}
{"id": "PMID:219730", "title": "Interaction of neuromuscular blocking effects of neomycin and polymyxin B.", "content": "Neomycin and polymyxin B produce neuromuscular blocks with distinct features by different mechanisms of action. In eight anesthetized cats the authors studied their interaction by examining the neuromuscular block produced by an equipotent mixture. Values of onset, potency, dose-response relations, duration and reversibility of block, the train-of-four and tetanic responses during block, the frequency-block relationships, and the posttetanic twitch behavior were well approximated by averaging the corresponding values previously reported for each antibiotic. Edrophonium, 0.2 mg/kg, reversed the block by 8 to 35 per cent. 4-Aminopyridine, 0.6 mg/kg, completely reversed the block and caused a long-lasting overshoot of the twitch response. The authors conclude that neomycin and polymyxin B are additive in neuromuscular effects, not only in terms of potency and duration, but also in terms of the characteristics of the blocks produced.", "contents": "Interaction of neuromuscular blocking effects of neomycin and polymyxin B. Neomycin and polymyxin B produce neuromuscular blocks with distinct features by different mechanisms of action. In eight anesthetized cats the authors studied their interaction by examining the neuromuscular block produced by an equipotent mixture. Values of onset, potency, dose-response relations, duration and reversibility of block, the train-of-four and tetanic responses during block, the frequency-block relationships, and the posttetanic twitch behavior were well approximated by averaging the corresponding values previously reported for each antibiotic. Edrophonium, 0.2 mg/kg, reversed the block by 8 to 35 per cent. 4-Aminopyridine, 0.6 mg/kg, completely reversed the block and caused a long-lasting overshoot of the twitch response. The authors conclude that neomycin and polymyxin B are additive in neuromuscular effects, not only in terms of potency and duration, but also in terms of the characteristics of the blocks produced."}
{"id": "PMID:219728", "title": "Failure of naloxone and naltrexone to antagonize halothane anesthesia in the dog.", "content": "The effects of two narcotic antagonists, naloxone and naltrexone, on minimum alveolar anesthetic concentration (MAC) were studied during halothane anesthesia in the dog. Following induction of anesthesia, MAC was determined in duplicate. Each dog was then given one of the two narcotic antagonists and MAC was redetermined in duplicate: five dogs were given naloxone, 3 mg/kg IV, followed by an intravenous infusion of naloxone, 0.025 mg/kg/min; five dogs received naltrexone, 5 mg/kg IV. MAC was unaffected by the narcotic antagonists. Failure of narcotic antagonists to reverse halothane anesthesia suggests that the endogenous opioid peptides are not involved in the anesthetic state produced by halothane.", "contents": "Failure of naloxone and naltrexone to antagonize halothane anesthesia in the dog. The effects of two narcotic antagonists, naloxone and naltrexone, on minimum alveolar anesthetic concentration (MAC) were studied during halothane anesthesia in the dog. Following induction of anesthesia, MAC was determined in duplicate. Each dog was then given one of the two narcotic antagonists and MAC was redetermined in duplicate: five dogs were given naloxone, 3 mg/kg IV, followed by an intravenous infusion of naloxone, 0.025 mg/kg/min; five dogs received naltrexone, 5 mg/kg IV. MAC was unaffected by the narcotic antagonists. Failure of narcotic antagonists to reverse halothane anesthesia suggests that the endogenous opioid peptides are not involved in the anesthetic state produced by halothane."}
{"id": "PMID:219732", "title": "Modifications of the immunofluorescence assay for feline leukemia virus group-specific antigens.", "content": "Observations and minor modifications are presented concerning the immunofluorescence assay for feline leukemia virus (FeLV) group-specific antigens (GSA) in blood cells of cats. Data are given regarding absorption of goat FeLV GSA antiserum in vivo in cats, absorption of the antiserum in vitro with feline blood cells, and the comparative efficacy of various chemical fixatives in preservation of FeLV GSA for immunofluorescent staining. The best results were obtained with in vitro absorption of antiserum and methanol fixation of FeLV GSA in blood smears.", "contents": "Modifications of the immunofluorescence assay for feline leukemia virus group-specific antigens. Observations and minor modifications are presented concerning the immunofluorescence assay for feline leukemia virus (FeLV) group-specific antigens (GSA) in blood cells of cats. Data are given regarding absorption of goat FeLV GSA antiserum in vivo in cats, absorption of the antiserum in vitro with feline blood cells, and the comparative efficacy of various chemical fixatives in preservation of FeLV GSA for immunofluorescent staining. The best results were obtained with in vitro absorption of antiserum and methanol fixation of FeLV GSA in blood smears."}
{"id": "PMID:219733", "title": "Isolation and identification of a bovine adenovirus type 3 with an adenovirus-associated virus.", "content": "A bovine adenovirus with agglutinating activity was isolated from feedlot calves and classified as serotype 3. The agglutinating activity was shown to be the property of an adenovirus-associated virus (AAV). The AAV was isolated from the bovine adenovirus by isopycnic centrifugation in CsCl; the AAV had a density of 1.4 g/cm2. This AAV is serologically related to bovine AAV-TR-15, but is distinct from bovine parvovirus-1 and primate AAV types 1 to 4, using counterimmunoelectrophoresis and hemagglutination-inhibition.", "contents": "Isolation and identification of a bovine adenovirus type 3 with an adenovirus-associated virus. A bovine adenovirus with agglutinating activity was isolated from feedlot calves and classified as serotype 3. The agglutinating activity was shown to be the property of an adenovirus-associated virus (AAV). The AAV was isolated from the bovine adenovirus by isopycnic centrifugation in CsCl; the AAV had a density of 1.4 g/cm2. This AAV is serologically related to bovine AAV-TR-15, but is distinct from bovine parvovirus-1 and primate AAV types 1 to 4, using counterimmunoelectrophoresis and hemagglutination-inhibition."}
{"id": "PMID:219734", "title": "Indirect solid-phase microradioimmunoassay for detection of pseudorabies virus antibody in swine sera.", "content": "An indirect solid-phase microradioimmunoassay (IRIA) was developed for detection and quantitation of antibodies to pseudorabies virus (PRV) in swine serum. Qualitative results of the IRIA compared closely with results of the serum neutralization test (NT) and the microimmunodiffusion test (MIDT). The IRIA was more sensitive than the NT for detection of antibodies to PRV in swine serum. The IRIA result is expressed numerically. With the IRIA and NT, antibody to PRV was first detectable in 3 experimentally infected pigs at 9 days after inoculation. With MIDT, antibody was detected in the 3 experimentally infected pigs at 9 days after inoculation. With the MIDT, antibody was detected in the 3 experimentally infected pigs at 7, 8, and 9 days after inoculation. The IRIA results are obtainable within a few hours; the NT and MIDT require 48 hours for completion.", "contents": "Indirect solid-phase microradioimmunoassay for detection of pseudorabies virus antibody in swine sera. An indirect solid-phase microradioimmunoassay (IRIA) was developed for detection and quantitation of antibodies to pseudorabies virus (PRV) in swine serum. Qualitative results of the IRIA compared closely with results of the serum neutralization test (NT) and the microimmunodiffusion test (MIDT). The IRIA was more sensitive than the NT for detection of antibodies to PRV in swine serum. The IRIA result is expressed numerically. With the IRIA and NT, antibody to PRV was first detectable in 3 experimentally infected pigs at 9 days after inoculation. With MIDT, antibody was detected in the 3 experimentally infected pigs at 9 days after inoculation. With the MIDT, antibody was detected in the 3 experimentally infected pigs at 7, 8, and 9 days after inoculation. The IRIA results are obtainable within a few hours; the NT and MIDT require 48 hours for completion."}
{"id": "PMID:219735", "title": "Isolation of bovine adenovirus type 7 from calves with pneumonia and enteritis.", "content": "Bovine adenovirus type 7 was isolated from a 10-month-old calf with fibrinopurulent pneumonia and from 2 newborn calves with pneumoenteritis. The viruses were isolated on calf lung and adrenal gland cell cultures and were identified as serotype 7 by immunoelectron microscopy and serum-neutralization tests.", "contents": "Isolation of bovine adenovirus type 7 from calves with pneumonia and enteritis. Bovine adenovirus type 7 was isolated from a 10-month-old calf with fibrinopurulent pneumonia and from 2 newborn calves with pneumoenteritis. The viruses were isolated on calf lung and adrenal gland cell cultures and were identified as serotype 7 by immunoelectron microscopy and serum-neutralization tests."}
{"id": "PMID:219736", "title": "The influence of cell type and lymph node metastases on survival of patients with carcinoma of the lung undergoing thoracotomy.", "content": "We studied 202 cases of bronchogenic carcinoma treated surgically between January 1, 1966 and December 31, 1970. Over all, adenocarcinoma was the most common cell type (36.1 per cent). Of 151 patients whose carcinomas were successfully resected, and who lived for at least 30 days postoperatively, 88 had lymph nodes free of cancer. Not surprisingly, 5-year survival was related to lymph node metatases and cell type. The best over-all 5-year survival rate was for large cell carcinoma; it was 52.0 per cent without nodal involvement. Similar figures for epidermoid carcinoma were 29.0 per cent over all, and 26.3 per cent without lymph node involvement; for adenocarcinoma, 19.3 per cent over all, and 32.0 per cent without nodal involvement. For the entire group of 151 patients, the 5-year survival rate was 27.8 per cent over all, and 36.4 per cent without nodal metastases. Among resected patients with mediastinal lymph nodes positive for cancer, the 5-year survival rates were 1 of 10 patients with large cell carcinoma, 1 of 19 patients with adenocarcinoma, and 3 of 12 patients with epidermoid carcinoma. This suggests that in patients with epidermoid carcinoma, the presence of mediastinal lymph node metastases is not, in itself, an absolute contraindication to resectional therapy.", "contents": "The influence of cell type and lymph node metastases on survival of patients with carcinoma of the lung undergoing thoracotomy. We studied 202 cases of bronchogenic carcinoma treated surgically between January 1, 1966 and December 31, 1970. Over all, adenocarcinoma was the most common cell type (36.1 per cent). Of 151 patients whose carcinomas were successfully resected, and who lived for at least 30 days postoperatively, 88 had lymph nodes free of cancer. Not surprisingly, 5-year survival was related to lymph node metatases and cell type. The best over-all 5-year survival rate was for large cell carcinoma; it was 52.0 per cent without nodal involvement. Similar figures for epidermoid carcinoma were 29.0 per cent over all, and 26.3 per cent without lymph node involvement; for adenocarcinoma, 19.3 per cent over all, and 32.0 per cent without nodal involvement. For the entire group of 151 patients, the 5-year survival rate was 27.8 per cent over all, and 36.4 per cent without nodal metastases. Among resected patients with mediastinal lymph nodes positive for cancer, the 5-year survival rates were 1 of 10 patients with large cell carcinoma, 1 of 19 patients with adenocarcinoma, and 3 of 12 patients with epidermoid carcinoma. This suggests that in patients with epidermoid carcinoma, the presence of mediastinal lymph node metastases is not, in itself, an absolute contraindication to resectional therapy."}
{"id": "PMID:219737", "title": "Growth of herpes simplex and cytomegalovirus in cultured human alveolar macrophages.", "content": "In laboratory animals, macrophages play a central role in controlling certain viral infections. Because the adult human lung is more susceptible to infection with cytomegalovirus than herpes simplex virus, we compared the replication of these two viruses in vitro in human alveolar macrophages. The growth of herpes simplex virus in alveolar macrophages was extremely limited, peak titers being only 1.8-fold greater than adsorbed virus titers. Cytomegalovirus, on the other hand, replicated in normal adult alveolar macrophages to the same extent as in permissive tissue culture cell. These data suggest that the human alveolar macrophage may play a central role in the control of lung infection with herpes simplex virus.", "contents": "Growth of herpes simplex and cytomegalovirus in cultured human alveolar macrophages. In laboratory animals, macrophages play a central role in controlling certain viral infections. Because the adult human lung is more susceptible to infection with cytomegalovirus than herpes simplex virus, we compared the replication of these two viruses in vitro in human alveolar macrophages. The growth of herpes simplex virus in alveolar macrophages was extremely limited, peak titers being only 1.8-fold greater than adsorbed virus titers. Cytomegalovirus, on the other hand, replicated in normal adult alveolar macrophages to the same extent as in permissive tissue culture cell. These data suggest that the human alveolar macrophage may play a central role in the control of lung infection with herpes simplex virus."}
{"id": "PMID:219738", "title": "Fine structure of the Legionnaires' disease bacterium. In-vitro and in-vivo studies of four isolates.", "content": "We obtained four bacterial isolates from patients with Legionnaires' disease and examined them for in-vitro and in-vivo fine-structure characteristics. All isolates had an outer membrane, cytoplasmic membrane, and intracellular membrane structure. Numerous intracellular inclusions were seen, particularly from in-vivo specimens, and appeared membrane-limited. Fine-structure analysis did not reveal the presence of a definitive peptidoglycan structure. Isolation, purification, and chemical analysis of Legionnaires' disease bacterium pepdoglycan established molar ratios of alanine-glutamic acid and muramic acid-glucosamine. Diaminopimelic acid was absent in the Legionnaires' disease bacterium peptidoglycan. The Kellenberger procedure for fixation appears to be the best method for the fine-structure determination of Legionnaires' disease bacteria.", "contents": "Fine structure of the Legionnaires' disease bacterium. In-vitro and in-vivo studies of four isolates. We obtained four bacterial isolates from patients with Legionnaires' disease and examined them for in-vitro and in-vivo fine-structure characteristics. All isolates had an outer membrane, cytoplasmic membrane, and intracellular membrane structure. Numerous intracellular inclusions were seen, particularly from in-vivo specimens, and appeared membrane-limited. Fine-structure analysis did not reveal the presence of a definitive peptidoglycan structure. Isolation, purification, and chemical analysis of Legionnaires' disease bacterium pepdoglycan established molar ratios of alanine-glutamic acid and muramic acid-glucosamine. Diaminopimelic acid was absent in the Legionnaires' disease bacterium peptidoglycan. The Kellenberger procedure for fixation appears to be the best method for the fine-structure determination of Legionnaires' disease bacteria."}
{"id": "PMID:219742", "title": "Gastrointestinal hormones in clinical disease: recent developments.", "content": "With the advent of radioimmunoassay and immunocytochemical methods, the peptides of the gastrointestinal tract have been identified and measured. Gastrinoma and insulinoma syndromes have been wall characterized. The pancreatic cholera syndrome and some of the evidence that the major manifestations of this disease may be mediated by vasoactive intestinal peptide have been re-examined. Pancreatic polypeptide seems to be an ideal peptide for study of vagal-cholinergic mechanisms that regulate hormone release; it also appears to be a tumor marker for several types of pancreatic endocrine tumors, particularly those of pancreatic cholera. Secretin and cholecystokinin are important regulators of pancreatic exocrine secretion and have been used to test pancreatic function, but there is little evidence that they account for clinical disease. Glucagon-secreting tumors produce a clinical syndrome of diabetes mellitus and distinctive skin lesions, which can be cured by tumor resection. Hormone-secreting tumors may provide insight into normal gut physiology.", "contents": "Gastrointestinal hormones in clinical disease: recent developments. With the advent of radioimmunoassay and immunocytochemical methods, the peptides of the gastrointestinal tract have been identified and measured. Gastrinoma and insulinoma syndromes have been wall characterized. The pancreatic cholera syndrome and some of the evidence that the major manifestations of this disease may be mediated by vasoactive intestinal peptide have been re-examined. Pancreatic polypeptide seems to be an ideal peptide for study of vagal-cholinergic mechanisms that regulate hormone release; it also appears to be a tumor marker for several types of pancreatic endocrine tumors, particularly those of pancreatic cholera. Secretin and cholecystokinin are important regulators of pancreatic exocrine secretion and have been used to test pancreatic function, but there is little evidence that they account for clinical disease. Glucagon-secreting tumors produce a clinical syndrome of diabetes mellitus and distinctive skin lesions, which can be cured by tumor resection. Hormone-secreting tumors may provide insight into normal gut physiology."}
{"id": "PMID:219743", "title": "The Cushing syndromes: changing views of diagnosis and treatment.", "content": "Cushing's syndrome is the common clinical presentation of three unique disorders that give rise to hypercortisolism. In most cases neoplasms underly each of these disorders. Clinical features are highly variable and not accounted for by cortisol alone; indeed, the multihormonal basis for much of the clinical syndrome remains uncertain. Demonstration of sustained, excessive cortisol production is essential and depends on a pattern of repeated measurements and several different procedures. Plasma adrenocorticotropin, although not helpful in establishing the diagnosis, has proved valuable in differentiating the three major entities that cause hypercortisolism. The renewed significance of pituitary microadenomas and their improved detection by sella tomography has accompanied recent, impressive advances in transsphenoidal microsurgery. This may become the preferred treatment for pituitary Cushing's syndrome in the adult, particularly where the appropriate equipment and skills are available; for children, external pituitary irradiation seems to offer safe and effective therapy.", "contents": "The Cushing syndromes: changing views of diagnosis and treatment. Cushing's syndrome is the common clinical presentation of three unique disorders that give rise to hypercortisolism. In most cases neoplasms underly each of these disorders. Clinical features are highly variable and not accounted for by cortisol alone; indeed, the multihormonal basis for much of the clinical syndrome remains uncertain. Demonstration of sustained, excessive cortisol production is essential and depends on a pattern of repeated measurements and several different procedures. Plasma adrenocorticotropin, although not helpful in establishing the diagnosis, has proved valuable in differentiating the three major entities that cause hypercortisolism. The renewed significance of pituitary microadenomas and their improved detection by sella tomography has accompanied recent, impressive advances in transsphenoidal microsurgery. This may become the preferred treatment for pituitary Cushing's syndrome in the adult, particularly where the appropriate equipment and skills are available; for children, external pituitary irradiation seems to offer safe and effective therapy."}
{"id": "PMID:219746", "title": "Clinical conditions mistaken for metastatic cancer to the choroid.", "content": "Thirteen patients who were referred to the Oncology Unit with the diagnosis of metastatic cancer to the choroid were studied and found to have other conditions. All of the patients were female. Nine of the 13 had a history of systemic cancer of which 6 were breast cancer. Five patients were currently being treated with chemotherapeutic agents for their systemic cancer. Three of the 13 patients had bilateral fundus lesions. The most common diagnostic entities confused with metastatic disease were either inflammatory or hemorrhagic lesions of the retina. The preceding history of cancer in the patient with a puzzling fundus lesion may predispose the referring ophthalmologist to suggest a diagnosis of metastatic cancer to the choroid.", "contents": "Clinical conditions mistaken for metastatic cancer to the choroid. Thirteen patients who were referred to the Oncology Unit with the diagnosis of metastatic cancer to the choroid were studied and found to have other conditions. All of the patients were female. Nine of the 13 had a history of systemic cancer of which 6 were breast cancer. Five patients were currently being treated with chemotherapeutic agents for their systemic cancer. Three of the 13 patients had bilateral fundus lesions. The most common diagnostic entities confused with metastatic disease were either inflammatory or hemorrhagic lesions of the retina. The preceding history of cancer in the patient with a puzzling fundus lesion may predispose the referring ophthalmologist to suggest a diagnosis of metastatic cancer to the choroid."}
{"id": "PMID:219749", "title": "Fibrous histiocytoma: benign and malignant variants.", "content": "Twenty cases of benign and malignant fibrous histiocytoma are presented. Six were benign, 11 malignant fibrous, and 3 pure malignant histiocytomas. These tumours arise from tissue histiocytes and have a wide range of histological appearances. The characteristic histological features are described and the variable clinical picture and different lines of treatment and management are discussed.", "contents": "Fibrous histiocytoma: benign and malignant variants. Twenty cases of benign and malignant fibrous histiocytoma are presented. Six were benign, 11 malignant fibrous, and 3 pure malignant histiocytomas. These tumours arise from tissue histiocytes and have a wide range of histological appearances. The characteristic histological features are described and the variable clinical picture and different lines of treatment and management are discussed."}
{"id": "PMID:219751", "title": "The experimental production of diarrhoea in colostrum deprived axenic and gnotoxenic calves with enteropathogenic Escherichia coli, rotavirus, coronavirus and in a combined infection of rotavirus and E. coli.", "content": "We attempted to produce diarrhoea experimentally in the newborn calf by orally injecting 17 colostrum-deprived calves with two serotypes of Escherichia coli Ent+ K99+, a rotavirus and a coronavirus. With E. coli alone, a dose of 2 x 10(8) bacteria administered 24 hours after birth causes a mild attack of diarrhoea, whereas 1 x 10(10) bacteria leads to dehydration and death. An inoculation of rotavirus is followed by diarrhoea which always contains large quantities of rotavirus. These animals were anorectic for a time, but none was dehydrated or died. With coronavirus, there were large quantities of watery diarrhoea, which led to dehydration and death. The inoculation of rotavirus, not lethal in itself, followed by a similarly non lethal inoculation of E. coli in doses of 3 x 10(8) to 2 x 10(9) led to dehydration and death. The authors conclude that dehydration and death of the animal can caused by large doses of E. coli or coronavirus or by two non-lethal doses of rotavirus and E. coli administered one after the other.", "contents": "The experimental production of diarrhoea in colostrum deprived axenic and gnotoxenic calves with enteropathogenic Escherichia coli, rotavirus, coronavirus and in a combined infection of rotavirus and E. coli. We attempted to produce diarrhoea experimentally in the newborn calf by orally injecting 17 colostrum-deprived calves with two serotypes of Escherichia coli Ent+ K99+, a rotavirus and a coronavirus. With E. coli alone, a dose of 2 x 10(8) bacteria administered 24 hours after birth causes a mild attack of diarrhoea, whereas 1 x 10(10) bacteria leads to dehydration and death. An inoculation of rotavirus is followed by diarrhoea which always contains large quantities of rotavirus. These animals were anorectic for a time, but none was dehydrated or died. With coronavirus, there were large quantities of watery diarrhoea, which led to dehydration and death. The inoculation of rotavirus, not lethal in itself, followed by a similarly non lethal inoculation of E. coli in doses of 3 x 10(8) to 2 x 10(9) led to dehydration and death. The authors conclude that dehydration and death of the animal can caused by large doses of E. coli or coronavirus or by two non-lethal doses of rotavirus and E. coli administered one after the other."}
{"id": "PMID:219747", "title": "[Lesions of the auditory nerve in leprosy (author's transl)].", "content": "A study of 260 male patients in the Alexandria leper colony showed that 15% of them had uni- or bilateral perception deafness. The lesion was of the retro-cochlear type and has to be related to lesions of the peripheral nerves.", "contents": "[Lesions of the auditory nerve in leprosy (author's transl)]. A study of 260 male patients in the Alexandria leper colony showed that 15% of them had uni- or bilateral perception deafness. The lesion was of the retro-cochlear type and has to be related to lesions of the peripheral nerves."}
{"id": "PMID:219752", "title": "Scanning electron microscopy of abomasium and intestine of gnotoxenic calves infected either with rotavirus, coronarivus or enteropathogenic Escherichia coli or with rotavirus and E. coli.", "content": "Neonatal calf diarrhoea induced with several agents of infection was studied by scanning electron microscopy. In a gnotoxenic calf infected with E. coli K99+ Ent+, slight lesions of the small intestine were observed and desquamation or puffiness of microvilli occurred. In rotavirus-infected calves, the abomasum was covered with abudant mucous film and appeared to be desquamated. In the small intestine, no desquamation of epithelium was observed. Inoculation of the rotavirus and E. coli induced severe diarrhoea. The whole digestive tract, even the abomasum and colon, was eroded. Coronavirus induced marked lesions in all levels of the intestine. These results demonstrate unequivocally the pathogenic properties of the three infectious agnets, the synergistic effect of E. coli and rotavirus. Furthermore, the importance of the abomasum in neonatal diarrhoea is emphasized.", "contents": "Scanning electron microscopy of abomasium and intestine of gnotoxenic calves infected either with rotavirus, coronarivus or enteropathogenic Escherichia coli or with rotavirus and E. coli. Neonatal calf diarrhoea induced with several agents of infection was studied by scanning electron microscopy. In a gnotoxenic calf infected with E. coli K99+ Ent+, slight lesions of the small intestine were observed and desquamation or puffiness of microvilli occurred. In rotavirus-infected calves, the abomasum was covered with abudant mucous film and appeared to be desquamated. In the small intestine, no desquamation of epithelium was observed. Inoculation of the rotavirus and E. coli induced severe diarrhoea. The whole digestive tract, even the abomasum and colon, was eroded. Coronavirus induced marked lesions in all levels of the intestine. These results demonstrate unequivocally the pathogenic properties of the three infectious agnets, the synergistic effect of E. coli and rotavirus. Furthermore, the importance of the abomasum in neonatal diarrhoea is emphasized."}
{"id": "PMID:219753", "title": "Cell-mediated cytotoxicity against hamster cells transformed by avian sarcoma viruses. 1. Description of the reaction.", "content": "The presence of new antigens on hamster cells transformed by avian sarcoma viruses was investigated by in vitro cellular microcytotoxicity assays using spleen cells obtained from immunized hamsters as effector cells and monolayers of transformed cells as targets. The effect of a number of variables was studied especially the concentration of effector cells and of target cells. Probit analysis has been used to statistical interpretation of data. Spleen cells obtained from hamsters immunized with RSV transformed rat cells have allowed the demonstration of new antigens on transformed hamster cells. These antigens have been also detected, in certain conditions, using effector cells obtained from hamsters immunized with RSV transformed hamster cells.", "contents": "Cell-mediated cytotoxicity against hamster cells transformed by avian sarcoma viruses. 1. Description of the reaction. The presence of new antigens on hamster cells transformed by avian sarcoma viruses was investigated by in vitro cellular microcytotoxicity assays using spleen cells obtained from immunized hamsters as effector cells and monolayers of transformed cells as targets. The effect of a number of variables was studied especially the concentration of effector cells and of target cells. Probit analysis has been used to statistical interpretation of data. Spleen cells obtained from hamsters immunized with RSV transformed rat cells have allowed the demonstration of new antigens on transformed hamster cells. These antigens have been also detected, in certain conditions, using effector cells obtained from hamsters immunized with RSV transformed hamster cells."}
{"id": "PMID:219754", "title": "Cell-mediated cytotoxicity against hamster cells transformed by avian sarcoma viruses. 2. Sensitivity of different subclones.", "content": "The presence of new antigens on different subclones of hamster cells transformed by avian sarcoma viruses was investigated by an in vitro cellular microcytotoxicity assay. The RS 2/3 and RS 2/10 subclones derived from the RS 2 clone, transformed with a Schmidt-Ruppin strain of RSV were highly sensitive to the cytotoxic action of spleen effector cells obtainled from hamsters immunized with RSV-transformed rat cells. The RS 2/6 subclone was sensitive only when 1,000 target cells were seeded and the RS 2/7 subclone was not susceptible to the cytotoxic action of effector cells. The RB 12/1 subclone, derived from the clone RB 12, transformed with a Bryan strain of RSV was poorly sensitive. The comparison between the sensitivity to XC-sensitized spleen cells of the different subclones and their other known properties was discussed.", "contents": "Cell-mediated cytotoxicity against hamster cells transformed by avian sarcoma viruses. 2. Sensitivity of different subclones. The presence of new antigens on different subclones of hamster cells transformed by avian sarcoma viruses was investigated by an in vitro cellular microcytotoxicity assay. The RS 2/3 and RS 2/10 subclones derived from the RS 2 clone, transformed with a Schmidt-Ruppin strain of RSV were highly sensitive to the cytotoxic action of spleen effector cells obtainled from hamsters immunized with RSV-transformed rat cells. The RS 2/6 subclone was sensitive only when 1,000 target cells were seeded and the RS 2/7 subclone was not susceptible to the cytotoxic action of effector cells. The RB 12/1 subclone, derived from the clone RB 12, transformed with a Bryan strain of RSV was poorly sensitive. The comparison between the sensitivity to XC-sensitized spleen cells of the different subclones and their other known properties was discussed."}
{"id": "PMID:219755", "title": "Behavioural and pituitary-adrenal characteristics of pigs differing by their susceptibility to the malignant hyperthermia syndrome induced by halothane anesthesia. 2. Pituitary-adrenal function.", "content": "Pituitary-adrenal function was investigated in two groups of Pietrain pigs differing by their susceptibility to the malignant hyperthermia syndrome induced by halothane, and in Large White pigs (LW). Plasma basal levels of glucocorticoids, measured by a protein binding technique, and plasma ACTH concentrations, determined by radioimmunoassay, did not differ according to halothane susceptibility but were higher in LW pigs compared with Pietrain pigs. The reactivity of the pituitary-adrenal axis to such stressors as exposition to a novel environment or shaking was the same for all experimental groups. The same was true concerning plasma levels of glucocorticoids and ACTH after injection of dexamethasone and response of the adrenal cortex to a standard dose of ACTH. These results demonstrate that LW pigs have a higher tonic secretion of ACTH than Pietrain pigs, but with identical phasic response to stimulations. Halothane susceptibility by itself appears to have no influence of pituitary-adrenal function.", "contents": "Behavioural and pituitary-adrenal characteristics of pigs differing by their susceptibility to the malignant hyperthermia syndrome induced by halothane anesthesia. 2. Pituitary-adrenal function. Pituitary-adrenal function was investigated in two groups of Pietrain pigs differing by their susceptibility to the malignant hyperthermia syndrome induced by halothane, and in Large White pigs (LW). Plasma basal levels of glucocorticoids, measured by a protein binding technique, and plasma ACTH concentrations, determined by radioimmunoassay, did not differ according to halothane susceptibility but were higher in LW pigs compared with Pietrain pigs. The reactivity of the pituitary-adrenal axis to such stressors as exposition to a novel environment or shaking was the same for all experimental groups. The same was true concerning plasma levels of glucocorticoids and ACTH after injection of dexamethasone and response of the adrenal cortex to a standard dose of ACTH. These results demonstrate that LW pigs have a higher tonic secretion of ACTH than Pietrain pigs, but with identical phasic response to stimulations. Halothane susceptibility by itself appears to have no influence of pituitary-adrenal function."}
{"id": "PMID:219762", "title": "Regulation of gastric acid secretion.", "content": "The three stimulants of gastric acid secretion likely to have physiological roles in regulation of secretion are acetylcholine, gastrin, and histamine. Acetylcholine is released by vagal and intramucosal reflex stimulation, acting directly on the parietal cell. Gastrin is released by peptides and free amino acids in the stomach and is the only known hormonal stimulant of acid secretion. Release of gastrin by acetylcholine may occur. However, cholinergic control of gastrin release is complex since under certain conditions anticholinergic drugs may actually enhance gastrin release. Factors regulating histamine release have not been defined, but studies with H2-receptor antagonists leave little doubt that histamine has an important role in acid secretion. Studies with isolated parietal cells indicate that histamine, gastrin, and acetylcholine each appear to act at separate receptors on the parietal cell. Anticholinergic agents specifically prevent the cellular actions of acetylcholine, cimetidine specifically inhibits stimulation by histamine, and neither inhibitor blocks the small direct response to gastrin. Furthermore potentiating interactions occur between histamine, gastrin, and cholinergic agents which may account for the interdependence of secretagogue action observed in vivo. Direct potentiating interactions occur between histamine and gastrin and histamine and carbachol but not between carbachol and gastrin. However, in the presence of histamine, carbachol, and gastrin, a three-way potentiation does occur. By interfering with the potentiating interactions between stimulants, anticholinergic agents and cimetidine display an apparent cross-specificity in vitro that resembles the effects of these agents in intact mucosa. The mechanisms underlying these interactions are unknown, but the actions of histamine appear to be mediated through increased production of cyclic AMP and cyclic AMP analogs, which mimic the interactions involving histamine itself. The secondary effectors for acetylcholine and gastrin and the mechanisms for amplification of the response to combinations of stimulants remain to be elucidated.", "contents": "Regulation of gastric acid secretion. The three stimulants of gastric acid secretion likely to have physiological roles in regulation of secretion are acetylcholine, gastrin, and histamine. Acetylcholine is released by vagal and intramucosal reflex stimulation, acting directly on the parietal cell. Gastrin is released by peptides and free amino acids in the stomach and is the only known hormonal stimulant of acid secretion. Release of gastrin by acetylcholine may occur. However, cholinergic control of gastrin release is complex since under certain conditions anticholinergic drugs may actually enhance gastrin release. Factors regulating histamine release have not been defined, but studies with H2-receptor antagonists leave little doubt that histamine has an important role in acid secretion. Studies with isolated parietal cells indicate that histamine, gastrin, and acetylcholine each appear to act at separate receptors on the parietal cell. Anticholinergic agents specifically prevent the cellular actions of acetylcholine, cimetidine specifically inhibits stimulation by histamine, and neither inhibitor blocks the small direct response to gastrin. Furthermore potentiating interactions occur between histamine, gastrin, and cholinergic agents which may account for the interdependence of secretagogue action observed in vivo. Direct potentiating interactions occur between histamine and gastrin and histamine and carbachol but not between carbachol and gastrin. However, in the presence of histamine, carbachol, and gastrin, a three-way potentiation does occur. By interfering with the potentiating interactions between stimulants, anticholinergic agents and cimetidine display an apparent cross-specificity in vitro that resembles the effects of these agents in intact mucosa. The mechanisms underlying these interactions are unknown, but the actions of histamine appear to be mediated through increased production of cyclic AMP and cyclic AMP analogs, which mimic the interactions involving histamine itself. The secondary effectors for acetylcholine and gastrin and the mechanisms for amplification of the response to combinations of stimulants remain to be elucidated."}
{"id": "PMID:219764", "title": "Cardiac heat production.", "content": "The energy production (heat + work) of cardiac muscle must be interpreted in terms of the major ATPases underwriting cardiac contraction; these are the Ca2+ and Na+-K+ transport ATPases and actomyosin ATPase. It is possible to apply the classical phenomenological subdivisions to cardiac energy production; when this is done, certain properties immediately distinguish cardiac muscle from skeletal muscle. Little or no temporal distinction exists between initial (anaerobic) and recovery (oxidative) metabolism. Even at temperatures as low as 20 degrees C most of the recovery heat is released within the time course of a single contraction. Cardiac muscle is characterized by a high resting heat rate, the magnitude of which varies between species and depends on the metabolic substrate. In isometric contractions there is a slightly curvilinear relationship between developed force and heat production. There is a tension-independent or activation component, the magnitude of which reflects the prevailing level of contractility and is probably associated with calcium release and retrieval. In isotonic contractions energy production is maximal when the muscle is heavily loaded but falls steeply when the size of the load is reduced. The enthalpy:load relation is probably similar to that found in twitch contractions of skeletal muscle working at room temperature or above; but, unlike for skeletal muscle, there are families of such curves: At any instant of time the relation depends upon the prevailing physiological conditions (e.g. stimulus rate, substrate supply, humoral agents, extracellular ionic concentrations, initial length). Cardiac energy production can be estimated by a variety of other techniques (such as high-energy phosphate utilization, oxygen consumption, and changes in tissue fluorescence related to pyridine nucleotide oxidation levels). At the present time there is considerable agreement between heat measurements and results obtained with these different techniques. We should like to conclude on a cautionary note. First, there is considerable variability in the properties of cardiac muscle from different species. Significant variations occur at nearly all levels of cellular function--e.g. shape of action potential, electrical and mechanical dependence upon stimulus history, mechanisms of excitation-contraction coupling, actomyosin ATPase activity, metabolic regulation, and differential sensitivity to anoxia or ischemia. Second, the types of contractions readily studied in isolated papillary muscles (i.e. isometric or isotonic twitches) may not necessarily be the best mechanical paradigms for understanding myocardial energetics in vivo. The particular geometric demands of individual research techniques require the use of a wide variety of myocardial preparations from a wide variety of species. This necessarily produces a pastiche view of cardiac muscle rather than an integrated picture of some hypothetically typical mammalian myocardium.", "contents": "Cardiac heat production. The energy production (heat + work) of cardiac muscle must be interpreted in terms of the major ATPases underwriting cardiac contraction; these are the Ca2+ and Na+-K+ transport ATPases and actomyosin ATPase. It is possible to apply the classical phenomenological subdivisions to cardiac energy production; when this is done, certain properties immediately distinguish cardiac muscle from skeletal muscle. Little or no temporal distinction exists between initial (anaerobic) and recovery (oxidative) metabolism. Even at temperatures as low as 20 degrees C most of the recovery heat is released within the time course of a single contraction. Cardiac muscle is characterized by a high resting heat rate, the magnitude of which varies between species and depends on the metabolic substrate. In isometric contractions there is a slightly curvilinear relationship between developed force and heat production. There is a tension-independent or activation component, the magnitude of which reflects the prevailing level of contractility and is probably associated with calcium release and retrieval. In isotonic contractions energy production is maximal when the muscle is heavily loaded but falls steeply when the size of the load is reduced. The enthalpy:load relation is probably similar to that found in twitch contractions of skeletal muscle working at room temperature or above; but, unlike for skeletal muscle, there are families of such curves: At any instant of time the relation depends upon the prevailing physiological conditions (e.g. stimulus rate, substrate supply, humoral agents, extracellular ionic concentrations, initial length). Cardiac energy production can be estimated by a variety of other techniques (such as high-energy phosphate utilization, oxygen consumption, and changes in tissue fluorescence related to pyridine nucleotide oxidation levels). At the present time there is considerable agreement between heat measurements and results obtained with these different techniques. We should like to conclude on a cautionary note. First, there is considerable variability in the properties of cardiac muscle from different species. Significant variations occur at nearly all levels of cellular function--e.g. shape of action potential, electrical and mechanical dependence upon stimulus history, mechanisms of excitation-contraction coupling, actomyosin ATPase activity, metabolic regulation, and differential sensitivity to anoxia or ischemia. Second, the types of contractions readily studied in isolated papillary muscles (i.e. isometric or isotonic twitches) may not necessarily be the best mechanical paradigms for understanding myocardial energetics in vivo. The particular geometric demands of individual research techniques require the use of a wide variety of myocardial preparations from a wide variety of species. This necessarily produces a pastiche view of cardiac muscle rather than an integrated picture of some hypothetically typical mammalian myocardium."}
{"id": "PMID:219761", "title": "The influence of different adjuvants on the production of IgD and IgE antibodies.", "content": "The aim of this study was to investigate the relationship between the synthesis of IgD and IgE antibodies upon the administration of antigen. Different adjuvants were used in order to find the optimal way of inducing in rats the synthesis of IgD and IgE antibodies. Ovalbumin was used as antigen. Fair amounts of IgE antibodies were produced using Al(OH)3 or Bordetella pertussis and Al(OH)3 as adjuvant. Only small quantities of IgE antibodies were formed when either Freund's complete adjuvant (FCA) or no adjuvant were used. IgD antibodies are formed upon the immunization with ovalbumin and FCA or B. pertussis in combination with Al(OH)3. Using Al(OH)3 alone as adjuvant or antigen alone resulted in only very minute quantities of specific IgD. Total serum IgE levels raised in the rats immunized with Al(OH)3 or B. pertussis and Al(OH)3. Total serum IgD was increased after immunization with ovalbumin and B. pertussis in combination with Al(OH)3.", "contents": "The influence of different adjuvants on the production of IgD and IgE antibodies. The aim of this study was to investigate the relationship between the synthesis of IgD and IgE antibodies upon the administration of antigen. Different adjuvants were used in order to find the optimal way of inducing in rats the synthesis of IgD and IgE antibodies. Ovalbumin was used as antigen. Fair amounts of IgE antibodies were produced using Al(OH)3 or Bordetella pertussis and Al(OH)3 as adjuvant. Only small quantities of IgE antibodies were formed when either Freund's complete adjuvant (FCA) or no adjuvant were used. IgD antibodies are formed upon the immunization with ovalbumin and FCA or B. pertussis in combination with Al(OH)3. Using Al(OH)3 alone as adjuvant or antigen alone resulted in only very minute quantities of specific IgD. Total serum IgE levels raised in the rats immunized with Al(OH)3 or B. pertussis and Al(OH)3. Total serum IgD was increased after immunization with ovalbumin and B. pertussis in combination with Al(OH)3."}
{"id": "PMID:219768", "title": "The biosynthesis and metabolism of prostaglandins.", "content": "With improved techniques for isolation and identification of materials, thromboxane (TXA2) and prostacyclin (PGI2) derivatives are now recognized as more abundant in some tissues and more potent than PGE2 and PGF2alpha. The rapid appearance and disappearance of these autacoids can be regulated at many points along the enzymatic path. Two important features affecting the rate of overall prostaglandin formation are the availability of non-esterified substrate and the availability of hydroperoxide activator for the cyclooxygenase. The fate of the endoperoxide formed by this reaction then depends upon the different relative amounts of the synthases and dehydrogenases in each type of synthesizing cell. Important future developments will indicate ways in which the amounts of these enzyme activities are altered and the ways in which the prostaglandin receptors interact with cellular adenyl cyclase and adrenergic receptors.", "contents": "The biosynthesis and metabolism of prostaglandins. With improved techniques for isolation and identification of materials, thromboxane (TXA2) and prostacyclin (PGI2) derivatives are now recognized as more abundant in some tissues and more potent than PGE2 and PGF2alpha. The rapid appearance and disappearance of these autacoids can be regulated at many points along the enzymatic path. Two important features affecting the rate of overall prostaglandin formation are the availability of non-esterified substrate and the availability of hydroperoxide activator for the cyclooxygenase. The fate of the endoperoxide formed by this reaction then depends upon the different relative amounts of the synthases and dehydrogenases in each type of synthesizing cell. Important future developments will indicate ways in which the amounts of these enzyme activities are altered and the ways in which the prostaglandin receptors interact with cellular adenyl cyclase and adrenergic receptors."}
{"id": "PMID:219769", "title": "Cellular mechanisms of prostaglandin action.", "content": "The human platelet and erythrocyte differ quite dramatically in relation to the arachidonic acid cascade. The platelet synthesizes its own characteristic products, while the erythrocyte lacks cyclo-oxygenase activity but possesses other metabolic enzymes. In these and other cell types the metabolites are potentially determined by the cascade enzymes, the availability of cofactors, the presence of specific activators and inhibitors, and the selective binding or transport of intermediates. Endogenously synthesized metabolites may have intracellular actions or may be released and exert their effects extracellularly. Study of the cellular mechanisms mediating these effects, like study of the fast-acting hormones, has focused primarily on the cyclic nucleotides and calcium. Considering the diverse activities of several metabolites in the platelet however, these mechanisms seem to need reevaluation or refining. The released cascade metabolites may also act as intercellular signals over a short range. The range depends on their chemical stability in the absence of protective carriers and their selective uptake and metabolism by surrounding cells. Additionally, the effects will reflect the selective interaction of responsive cells with the spectrum of metabolites released. Answering these questions of complex intercellular interactions requires the identification and classification of characteristic responses and the metabolic profile of individual cell types in each tissue. Consequently, this type of analysis may best be done with isolated cells, such as the platelet and erythrocyte.", "contents": "Cellular mechanisms of prostaglandin action. The human platelet and erythrocyte differ quite dramatically in relation to the arachidonic acid cascade. The platelet synthesizes its own characteristic products, while the erythrocyte lacks cyclo-oxygenase activity but possesses other metabolic enzymes. In these and other cell types the metabolites are potentially determined by the cascade enzymes, the availability of cofactors, the presence of specific activators and inhibitors, and the selective binding or transport of intermediates. Endogenously synthesized metabolites may have intracellular actions or may be released and exert their effects extracellularly. Study of the cellular mechanisms mediating these effects, like study of the fast-acting hormones, has focused primarily on the cyclic nucleotides and calcium. Considering the diverse activities of several metabolites in the platelet however, these mechanisms seem to need reevaluation or refining. The released cascade metabolites may also act as intercellular signals over a short range. The range depends on their chemical stability in the absence of protective carriers and their selective uptake and metabolism by surrounding cells. Additionally, the effects will reflect the selective interaction of responsive cells with the spectrum of metabolites released. Answering these questions of complex intercellular interactions requires the identification and classification of characteristic responses and the metabolic profile of individual cell types in each tissue. Consequently, this type of analysis may best be done with isolated cells, such as the platelet and erythrocyte."}
{"id": "PMID:219770", "title": "[Development of an accelerated method of determining the antibiotic sensitivity of Cl. perfringens type A].", "content": "An express method for determination of antibiotic sensitivity in the strains of Cl. perfringens of type A using Soviet dry nutrient media and antibiotics is proposed. The criteria for estimation of the level of the antibiotic sensitivity of the causative agent of gas gangrene in short periods on the basis of comparison of the data of the antibiotic agar diffusion procedure and the antibiotic MIC were worked out. Twelve antibiotics and 45 collection strains of Cl. perfringens of type A were used in the experiment. The antibiotic agar diffusion method with the use of the nutrient media, microbial load and cultivation conditions developed by the authors is recommended for tentative determination of the antibiotic sensitivity in Cl. perfringens of type A for 4 hours. The use of the agar diffusion method and determination of the antibiotic MIC provided complete estimation of tha antibiotic sensitivity of Cl. perfringens of type A within not more than 24 hours.", "contents": "[Development of an accelerated method of determining the antibiotic sensitivity of Cl. perfringens type A]. An express method for determination of antibiotic sensitivity in the strains of Cl. perfringens of type A using Soviet dry nutrient media and antibiotics is proposed. The criteria for estimation of the level of the antibiotic sensitivity of the causative agent of gas gangrene in short periods on the basis of comparison of the data of the antibiotic agar diffusion procedure and the antibiotic MIC were worked out. Twelve antibiotics and 45 collection strains of Cl. perfringens of type A were used in the experiment. The antibiotic agar diffusion method with the use of the nutrient media, microbial load and cultivation conditions developed by the authors is recommended for tentative determination of the antibiotic sensitivity in Cl. perfringens of type A for 4 hours. The use of the agar diffusion method and determination of the antibiotic MIC provided complete estimation of tha antibiotic sensitivity of Cl. perfringens of type A within not more than 24 hours."}
{"id": "PMID:219772", "title": "Fluid accumulation in mouse ligated intestine inoculated with Clostridium perfringens enterotoxin.", "content": "Clostridium perfringens enterotoxin, when inoculated into the ligated intestinal loop of mice, caused marked distension due to fluid accumulation. The increase in weight of the intestinal loop was proportional to the log dose of enterotoxin within a range from 1 to 16 micrograms. The fluid accumulation was arrested by washing the loop with saline or by injection of the specific anti-enterotoxin serum into the loop 5 or even 30 min after inoculation of the enterotoxin. A significant increase in weight of the loop was found as early as 10 min after inoculation of the toxin. These results may suggest that entergotoxin is neither bound firmly to the mucosal membrane nor permeates into the cells of the intestinal wall. The mouse intestinal loop test is economical, simple to perform, and applicable for quantitative determination of the enteropathogenic activity of C. perfringens enterotoxin.", "contents": "Fluid accumulation in mouse ligated intestine inoculated with Clostridium perfringens enterotoxin. Clostridium perfringens enterotoxin, when inoculated into the ligated intestinal loop of mice, caused marked distension due to fluid accumulation. The increase in weight of the intestinal loop was proportional to the log dose of enterotoxin within a range from 1 to 16 micrograms. The fluid accumulation was arrested by washing the loop with saline or by injection of the specific anti-enterotoxin serum into the loop 5 or even 30 min after inoculation of the enterotoxin. A significant increase in weight of the loop was found as early as 10 min after inoculation of the toxin. These results may suggest that entergotoxin is neither bound firmly to the mucosal membrane nor permeates into the cells of the intestinal wall. The mouse intestinal loop test is economical, simple to perform, and applicable for quantitative determination of the enteropathogenic activity of C. perfringens enterotoxin."}
{"id": "PMID:219773", "title": "Unsuitability of polioviruses as indicators of virological quality of water.", "content": "Polioviruses could not be detected in about 50% of sewage samples despite routine administration of live attenuated poliovirus vaccine to the infant population.", "contents": "Unsuitability of polioviruses as indicators of virological quality of water. Polioviruses could not be detected in about 50% of sewage samples despite routine administration of live attenuated poliovirus vaccine to the infant population."}
{"id": "PMID:219784", "title": "Persistence of herpes simplex virus types 1 and 2 in infected individuals.", "content": "During a 23-month period, 18 patients with facial or genital herpetic lesions were examined; culture specimens from each patient were obtained three times per week for virologic studies. The isolated viruses were identified, and the average duration of herpesvirus in lesions was determined. Herpes simplex virus type 1 (HSV-1) was isolated from facial lesions for a mean duration of 3 1/2 days. In contrast, herpes simplex virus type 2 (HSV-2) was isolated from genital lesions for a mean duration of 5 1/2 days. The duration of viral persistence in lesions of patients with mild primary infection did not seem to differ from that in patients with recurrent infection.", "contents": "Persistence of herpes simplex virus types 1 and 2 in infected individuals. During a 23-month period, 18 patients with facial or genital herpetic lesions were examined; culture specimens from each patient were obtained three times per week for virologic studies. The isolated viruses were identified, and the average duration of herpesvirus in lesions was determined. Herpes simplex virus type 1 (HSV-1) was isolated from facial lesions for a mean duration of 3 1/2 days. In contrast, herpes simplex virus type 2 (HSV-2) was isolated from genital lesions for a mean duration of 5 1/2 days. The duration of viral persistence in lesions of patients with mild primary infection did not seem to differ from that in patients with recurrent infection."}
{"id": "PMID:219787", "title": "Mitochondrial oxidative activity in human rheumatoid synovial lining cells.", "content": "The activities of two mitochondrial enzymes, succinate dehydrogenase and cytochrome oxidase, have been measured by quantitative cytochemistry and microdensitometry in the synoviocytes of rheumatoid and non-rheumatoid synovial lining cells. Although both tended to be higher in the former, there was no statistically significant difference in the activities of either enzyme in these tissues. However, when cytochrome oxidase activity was measured without exogenous cytochrome c, the activity in the rheumatoid synoviocytes was highly significantly elevated. It is suggested that these findings may indicate only that the cytochrome c-cytochrome oxidase complex in the rheumatoid cells is more stable, possibly because of the increased availability of phospholipids in these cells.", "contents": "Mitochondrial oxidative activity in human rheumatoid synovial lining cells. The activities of two mitochondrial enzymes, succinate dehydrogenase and cytochrome oxidase, have been measured by quantitative cytochemistry and microdensitometry in the synoviocytes of rheumatoid and non-rheumatoid synovial lining cells. Although both tended to be higher in the former, there was no statistically significant difference in the activities of either enzyme in these tissues. However, when cytochrome oxidase activity was measured without exogenous cytochrome c, the activity in the rheumatoid synoviocytes was highly significantly elevated. It is suggested that these findings may indicate only that the cytochrome c-cytochrome oxidase complex in the rheumatoid cells is more stable, possibly because of the increased availability of phospholipids in these cells."}
{"id": "PMID:219789", "title": "Cerebrospinal fluid lymphocyte transformations in meningitis.", "content": "Cerebrospinal fluid lymphocytes from 13 patients with nonsuppurative meningitis were cultured with antigens derived from Mycobacterium tuberculosis, Sporotrichum schenckii, and herpes simplex. When CSF lymphocytes from five patients with infections associated with these organisms were incubated with \"correct\" antigen there was increased incorporation of thymidine. The levels were higher than those seen when the cells were incubated with different antigens or when CSF lymphocytes from patients with other causes for their meningitis were cultured with these antigens. A compartmentalization of antigen-specific cells was suggested as CSF lymphocytes had greater stimulation than did peripheral blood lymphocytes from the same patient when incubated with the correct antigen. Transformational assays of CSF lymphocytes may provide a valuable diagnostic aid in certain cases of chronic meningitis.", "contents": "Cerebrospinal fluid lymphocyte transformations in meningitis. Cerebrospinal fluid lymphocytes from 13 patients with nonsuppurative meningitis were cultured with antigens derived from Mycobacterium tuberculosis, Sporotrichum schenckii, and herpes simplex. When CSF lymphocytes from five patients with infections associated with these organisms were incubated with \"correct\" antigen there was increased incorporation of thymidine. The levels were higher than those seen when the cells were incubated with different antigens or when CSF lymphocytes from patients with other causes for their meningitis were cultured with these antigens. A compartmentalization of antigen-specific cells was suggested as CSF lymphocytes had greater stimulation than did peripheral blood lymphocytes from the same patient when incubated with the correct antigen. Transformational assays of CSF lymphocytes may provide a valuable diagnostic aid in certain cases of chronic meningitis."}
{"id": "PMID:219786", "title": "Enzyme inhibition by tobacco smoke: a comparison of the effects of four filters.", "content": "The effects of four types of cigarette filters on the inhibition of glyceraldehyde-3-phosphate dehydrogenase by aqueous solutions of the free gas phase of tobacco smoke have been studied. Commercial cellulose acetate-charcoal filters or experimental wool filters containing a polyethyleneimine-quaternary ammonium additive were particularly effective in removing the inhibitor(s) from smoke under prescribed experimental conditions. Inhibition was dependent in all cases on both the age and the amount of free gas phase solution as well as contact time. Transient enzyme activation was observed. It is suggested that hydrogen sulfide is the main inhibitor present in the gas phase of cigarette smoke.", "contents": "Enzyme inhibition by tobacco smoke: a comparison of the effects of four filters. The effects of four types of cigarette filters on the inhibition of glyceraldehyde-3-phosphate dehydrogenase by aqueous solutions of the free gas phase of tobacco smoke have been studied. Commercial cellulose acetate-charcoal filters or experimental wool filters containing a polyethyleneimine-quaternary ammonium additive were particularly effective in removing the inhibitor(s) from smoke under prescribed experimental conditions. Inhibition was dependent in all cases on both the age and the amount of free gas phase solution as well as contact time. Transient enzyme activation was observed. It is suggested that hydrogen sulfide is the main inhibitor present in the gas phase of cigarette smoke."}
{"id": "PMID:219790", "title": "Pseudohypoparathyroidism: report on a family with four affected sisters.", "content": "A family consisting of a mother, a father with probable pseudopseudohypoparathyroidism (PPHP), two normal daughters, and four daughters with pseudohypoparathyroidism (PHP) have been observed for more than 15 years at North Carolina Memorial Hospital (NCMH). The studies performed on family members included (1) roentgenographic examinations of the chest, skull, hands, and soft tissues; (2) serum calcium, phosphorus, and immunoreactive parathyroid hormone measurements; (3) urinary cyclic adenosine 3'5'-monophosphate determinations following parathyroid injection; and (4) HLA and blood-type determinations. We review the genetic aspects of PHP. The findings in this family suggest an autosomal dominant mode of transmission in PHP.", "contents": "Pseudohypoparathyroidism: report on a family with four affected sisters. A family consisting of a mother, a father with probable pseudopseudohypoparathyroidism (PPHP), two normal daughters, and four daughters with pseudohypoparathyroidism (PHP) have been observed for more than 15 years at North Carolina Memorial Hospital (NCMH). The studies performed on family members included (1) roentgenographic examinations of the chest, skull, hands, and soft tissues; (2) serum calcium, phosphorus, and immunoreactive parathyroid hormone measurements; (3) urinary cyclic adenosine 3'5'-monophosphate determinations following parathyroid injection; and (4) HLA and blood-type determinations. We review the genetic aspects of PHP. The findings in this family suggest an autosomal dominant mode of transmission in PHP."}
{"id": "PMID:219793", "title": "Changes in signal transmission by neurons of the cat lateral geniculate nucleus by acute deafferentation and early degeneration.", "content": "1. The responses of single principal cells of the cat lateral geniculate nucleus (LGN) were recorded extracellulary from the optic radiation (OR) axons or intracellularly from the LGN. Electrical stimuli at different frequencies were applied to the optic tract (OT) to test the transneuronal and the synaptic signal transmission in the LGN. 2. The effect of acute deafferentation (by photocoagulation of the retinal receptive field) or of synaptic degeneration induced 2-4 days prior to the recording time on the LGN neuron signal transfer was studied. Immediately after deafferentation, the synaptic signal transfer by LGN neurons exhibits signs of hyperexcitability leading to multiple neuronal discharges. This acute deafferentation hyperexicitability is probably caused mainly by the disapperance of lateral inhibition mediated by LGN interneurons. The deafferentation hyperexcitability disappeared during electrical stimulation of the OT at frequencies greater than 10/sec. 3. With progressing degeneration of the synaptic terminals during the 2nd to 4th day after interruption of the optic nerve axoplasmic flow, the synaptic signal transfer by LGN neurons gradually deteriorates and ceases at the end of the fourth day. The signs of this deterioration (larger temporal scatter, increased exhaustability and reduced upper frequency limit of the transneuronal signal transmission and gradual reduction of the EPSP amplitude in D-neurons) were quantitatively investigated. 4. The neurophysiological data obtained at different levels of synaptic terminal degeneration are well correlated with morphological changes found within the degenerating synaptic terminals.", "contents": "Changes in signal transmission by neurons of the cat lateral geniculate nucleus by acute deafferentation and early degeneration. 1. The responses of single principal cells of the cat lateral geniculate nucleus (LGN) were recorded extracellulary from the optic radiation (OR) axons or intracellularly from the LGN. Electrical stimuli at different frequencies were applied to the optic tract (OT) to test the transneuronal and the synaptic signal transmission in the LGN. 2. The effect of acute deafferentation (by photocoagulation of the retinal receptive field) or of synaptic degeneration induced 2-4 days prior to the recording time on the LGN neuron signal transfer was studied. Immediately after deafferentation, the synaptic signal transfer by LGN neurons exhibits signs of hyperexcitability leading to multiple neuronal discharges. This acute deafferentation hyperexicitability is probably caused mainly by the disapperance of lateral inhibition mediated by LGN interneurons. The deafferentation hyperexcitability disappeared during electrical stimulation of the OT at frequencies greater than 10/sec. 3. With progressing degeneration of the synaptic terminals during the 2nd to 4th day after interruption of the optic nerve axoplasmic flow, the synaptic signal transfer by LGN neurons gradually deteriorates and ceases at the end of the fourth day. The signs of this deterioration (larger temporal scatter, increased exhaustability and reduced upper frequency limit of the transneuronal signal transmission and gradual reduction of the EPSP amplitude in D-neurons) were quantitatively investigated. 4. The neurophysiological data obtained at different levels of synaptic terminal degeneration are well correlated with morphological changes found within the degenerating synaptic terminals."}
{"id": "PMID:219796", "title": "[Structure of inclusion bodies and electron microscopic virus detection in naturally occurring inclusion body hepatitis in chickens].", "content": "Electron microscopy was used to examine the liver of chickens with spontaneous inclusion body hepatitis. Eosinophilic inclusion bodies only were established from two flocks, mainly amphophilic from one flock, and primarily basophilic from another two flocks. Eosinophilic inclusion bodies were predominant in broiler chickens with dystrophic fatty degeneration of the liver, while basophile inclusion bodies were recorded primarily from parental or laying-hen chickens with reduced metabolic stress of the liver and more focal necrosis. The eosinophilic inclusion bodies consitsed of a filamentous matrix, with virus particles not safely detectable. The amphophilic inclusion bodies contained parvovirus particles, most likely adenoassociated virus, while the basophilic inclusion bodies inclused parvoviruses or adenoviruses (in flock NO. IV) or adenoviruses only (in flock No. V) in an amorphous chromatin matrix. The presence of parvoviruses in field material was taken to suggest a possible role of those pathogens in inclusion body hepatitis.", "contents": "[Structure of inclusion bodies and electron microscopic virus detection in naturally occurring inclusion body hepatitis in chickens]. Electron microscopy was used to examine the liver of chickens with spontaneous inclusion body hepatitis. Eosinophilic inclusion bodies only were established from two flocks, mainly amphophilic from one flock, and primarily basophilic from another two flocks. Eosinophilic inclusion bodies were predominant in broiler chickens with dystrophic fatty degeneration of the liver, while basophile inclusion bodies were recorded primarily from parental or laying-hen chickens with reduced metabolic stress of the liver and more focal necrosis. The eosinophilic inclusion bodies consitsed of a filamentous matrix, with virus particles not safely detectable. The amphophilic inclusion bodies contained parvovirus particles, most likely adenoassociated virus, while the basophilic inclusion bodies inclused parvoviruses or adenoviruses (in flock NO. IV) or adenoviruses only (in flock No. V) in an amorphous chromatin matrix. The presence of parvoviruses in field material was taken to suggest a possible role of those pathogens in inclusion body hepatitis."}
{"id": "PMID:219797", "title": "[Necrotizing enteritis in suckling pigs (Clostridium perfringens type C enterotoxemia). II. Toxin formation, heat and drug resistance of Clostridium perfringens strains isolated from suckling pigs and broilers with necrotizing enteritis].", "content": "Nineteen Clostridium perfringens Type C strains and ten foreign control strains of subtypes C1, C3, and C4 were tested for their toxin formation and spore resistance to heat. The 19 Type C strains had been isolated from unweaned piglets in the context of necrotising enteritis outbreaks in the GDR. The Clostridium perfringens Type C strains formed beta-toxin, but they failed to form epsilon-toxin or gamma-toxin, alpha-toxin was successfully recorded from 15 of the 19 strains tested from unweaned piglets. The minor-lethal toxin fractions were also tested, with delta-toxin being recorded from all strains, non-alpha-delta-theta-toxin from six, theta-toxin from five, and K-toxin from one. Tests for delta-toxin, lambda-toxin, and mu-toxin were negative. The Clostridium perfringens Type C strains isolated in the GDR from unweaned piglets with necrotising enteritis were, basically, identical with those described in Denmark by von Hogh (1967) with regard to toxin formation. Clostridium perfringens strains cultured in broilers with necrotising enteritis were characterised by regular toxin production in the context of alpha, theta, delta as well as non-alpha-delta-theta. They failed to form beta, epsilon, gamma and lambda, while mu-toxin was formed by them quite irregularly. They, consequently, are Type A strains. Resistance to chloramphenicol and/or oxytetracycline was exhibited by 78.5 per cent of 237 tested Clostridium perfringens strains which had been isolated from unweaned piglets and broilers with necrotosing enteritis. Multiple resistance was recorded from 33.9 per cent. All strains were susceptible to penicillin, nitrofurantoin, and erythromycin.", "contents": "[Necrotizing enteritis in suckling pigs (Clostridium perfringens type C enterotoxemia). II. Toxin formation, heat and drug resistance of Clostridium perfringens strains isolated from suckling pigs and broilers with necrotizing enteritis]. Nineteen Clostridium perfringens Type C strains and ten foreign control strains of subtypes C1, C3, and C4 were tested for their toxin formation and spore resistance to heat. The 19 Type C strains had been isolated from unweaned piglets in the context of necrotising enteritis outbreaks in the GDR. The Clostridium perfringens Type C strains formed beta-toxin, but they failed to form epsilon-toxin or gamma-toxin, alpha-toxin was successfully recorded from 15 of the 19 strains tested from unweaned piglets. The minor-lethal toxin fractions were also tested, with delta-toxin being recorded from all strains, non-alpha-delta-theta-toxin from six, theta-toxin from five, and K-toxin from one. Tests for delta-toxin, lambda-toxin, and mu-toxin were negative. The Clostridium perfringens Type C strains isolated in the GDR from unweaned piglets with necrotising enteritis were, basically, identical with those described in Denmark by von Hogh (1967) with regard to toxin formation. Clostridium perfringens strains cultured in broilers with necrotising enteritis were characterised by regular toxin production in the context of alpha, theta, delta as well as non-alpha-delta-theta. They failed to form beta, epsilon, gamma and lambda, while mu-toxin was formed by them quite irregularly. They, consequently, are Type A strains. Resistance to chloramphenicol and/or oxytetracycline was exhibited by 78.5 per cent of 237 tested Clostridium perfringens strains which had been isolated from unweaned piglets and broilers with necrotosing enteritis. Multiple resistance was recorded from 33.9 per cent. All strains were susceptible to penicillin, nitrofurantoin, and erythromycin."}
{"id": "PMID:219798", "title": "[Electrocardiographic functional diagnosis of the vegitative nervous system in cattle. 2. Determination of the propranolol blockade effect on cardiac beta-receptors under application of maximum isoprenaline doses].", "content": "The blocking effects of 50 mg and 100 mg of propanolol, a beta-receptor blocker, upon the beta-adrenergic receptors of cattle heart were verified by means of 250 microgram of isoprenaline, a maximum dose. The 50-mg-propanolol dose inhibited between 77 and 80 per cent of the isoprenaline-caused QT reduction, whic action was considered as being sufficiently safe to rule out any beta-adrenergic cardiac effect. Blockade was further increased to the order of between 89 and 92 per cent by using 100 mg of propanolol, but certain side-effects occurred (expiratory dyspnoe, quinidinlike action in terms of PQ extension, and vagovasal collapse). Therefore, 50 mg of propanolol are recommended as the proper dosage with which to examine cardiac and extracardiac beta-adrenergic receptors in cattle. Application of propanolol to non-anaesthetised, nonatropinised cattle resulted in higher bloackade of isoprenaline-caused QT reduction, as compared to the parameters PQ, TP, TQ, time of cardiac action, PP, and momentary heart rate. This phenomenon is being analysed. With reference being made to the peculiarities of sympathico-parasympathetic interactions on the heart, QT time is considered as a more safe parameter by which to assess substrate competition between propanolol and isoprenaline at cardiac beta-receptors, while the ventriculodiastolic ECG recordings TQ, TP, and PQ as well as time of cardiac action, PP and momentary heart rate might come under a somewhat stronger influence of the parasympathetic system.", "contents": "[Electrocardiographic functional diagnosis of the vegitative nervous system in cattle. 2. Determination of the propranolol blockade effect on cardiac beta-receptors under application of maximum isoprenaline doses]. The blocking effects of 50 mg and 100 mg of propanolol, a beta-receptor blocker, upon the beta-adrenergic receptors of cattle heart were verified by means of 250 microgram of isoprenaline, a maximum dose. The 50-mg-propanolol dose inhibited between 77 and 80 per cent of the isoprenaline-caused QT reduction, whic action was considered as being sufficiently safe to rule out any beta-adrenergic cardiac effect. Blockade was further increased to the order of between 89 and 92 per cent by using 100 mg of propanolol, but certain side-effects occurred (expiratory dyspnoe, quinidinlike action in terms of PQ extension, and vagovasal collapse). Therefore, 50 mg of propanolol are recommended as the proper dosage with which to examine cardiac and extracardiac beta-adrenergic receptors in cattle. Application of propanolol to non-anaesthetised, nonatropinised cattle resulted in higher bloackade of isoprenaline-caused QT reduction, as compared to the parameters PQ, TP, TQ, time of cardiac action, PP, and momentary heart rate. This phenomenon is being analysed. With reference being made to the peculiarities of sympathico-parasympathetic interactions on the heart, QT time is considered as a more safe parameter by which to assess substrate competition between propanolol and isoprenaline at cardiac beta-receptors, while the ventriculodiastolic ECG recordings TQ, TP, and PQ as well as time of cardiac action, PP and momentary heart rate might come under a somewhat stronger influence of the parasympathetic system."}
{"id": "PMID:219799", "title": "[Effects of the main derivatives of vitmain D in 3 siblings with \"pseudo-deficiency\" rickets].", "content": "Three siblings, respectively 20, 16 and 12 years old, presented with hypocalcemic vitamin D resistant rickets (Prader's type). Their clinical history included several periods of spontaneous cessation of therapy, with severe relapses. Since 1973, treatment was strictly observed, allowing to test the therapeutic effects of 25 OH D3, 1-25 (OH) 2 D3 and 1-alpha (OH) D3. The clinical effects are reported as well as biochemical data. Among them, an inactive form of hyperparathyroidism is emphasized, which may resemble some cases of pseudohypoparathyroidism. Simultaneous resistance to exogenous PTE was also demonstraded.", "contents": "[Effects of the main derivatives of vitmain D in 3 siblings with \"pseudo-deficiency\" rickets]. Three siblings, respectively 20, 16 and 12 years old, presented with hypocalcemic vitamin D resistant rickets (Prader's type). Their clinical history included several periods of spontaneous cessation of therapy, with severe relapses. Since 1973, treatment was strictly observed, allowing to test the therapeutic effects of 25 OH D3, 1-25 (OH) 2 D3 and 1-alpha (OH) D3. The clinical effects are reported as well as biochemical data. Among them, an inactive form of hyperparathyroidism is emphasized, which may resemble some cases of pseudohypoparathyroidism. Simultaneous resistance to exogenous PTE was also demonstraded."}
{"id": "PMID:219800", "title": "[Herpetic meningoencephalitis in infants. Study of 7 cases].", "content": "Seven children with herpes meningoencephalitis aged between 14 days and 13 months were studied. The herpes infection was confirmed by isolation of herpes virus from the CSF (one case), from the brain (one case), and in the 5 remaining cases by serology. The strains isolated were herpes type 2. The clinical features of herpes meningoencephalitis in the first year of life and the laboratory data are described.", "contents": "[Herpetic meningoencephalitis in infants. Study of 7 cases]. Seven children with herpes meningoencephalitis aged between 14 days and 13 months were studied. The herpes infection was confirmed by isolation of herpes virus from the CSF (one case), from the brain (one case), and in the 5 remaining cases by serology. The strains isolated were herpes type 2. The clinical features of herpes meningoencephalitis in the first year of life and the laboratory data are described."}
{"id": "PMID:219801", "title": "[Characterization and solubilization of specific growth hormone binding sites in the rat liver].", "content": "The interaction of 125I-labeled human growth hormone (HGH) with microsomal membranes of female rat liver is a specific, saturable and reversible process; at saturation, about 0.9 picomoles of 125I-HGH are bound per mg of membrane proteins. Equilibrium is achieved after 90 minutes of incubation. The binding is dependent on membrane concentration and pH of the incubation medium. Membrane treatment by phospholipase A causes a 1.5 fold increase in binding capacity. 125I-HGH exposed to membranes or eluted from the membrane-receptor complex retains biological activity as tested by binding to liver membranes. The variation in binding with the age of the female rat is probably related to a change in the binding capacity and not in the binding affinity. Microsomal membranes can be solubilized by the use of Triton X-100; solubilized membranes retain their capacity to bind HGH and the properties of the interaction are similar to the ones of the particulate membranes. Lactogenic and somatogenic receptors are eluted from an acrylamide-agarose column in the same position; their apparent molecular weight is 350,000.", "contents": "[Characterization and solubilization of specific growth hormone binding sites in the rat liver]. The interaction of 125I-labeled human growth hormone (HGH) with microsomal membranes of female rat liver is a specific, saturable and reversible process; at saturation, about 0.9 picomoles of 125I-HGH are bound per mg of membrane proteins. Equilibrium is achieved after 90 minutes of incubation. The binding is dependent on membrane concentration and pH of the incubation medium. Membrane treatment by phospholipase A causes a 1.5 fold increase in binding capacity. 125I-HGH exposed to membranes or eluted from the membrane-receptor complex retains biological activity as tested by binding to liver membranes. The variation in binding with the age of the female rat is probably related to a change in the binding capacity and not in the binding affinity. Microsomal membranes can be solubilized by the use of Triton X-100; solubilized membranes retain their capacity to bind HGH and the properties of the interaction are similar to the ones of the particulate membranes. Lactogenic and somatogenic receptors are eluted from an acrylamide-agarose column in the same position; their apparent molecular weight is 350,000."}
{"id": "PMID:219802", "title": "Estrogen therapy for severe persistent depressions in women.", "content": "Positive results are reported from a double-blind study of estrogen therapy administered to severely depressed, inpatient women who had failed to respond to various conventional treatments of depression. Large doses of oral conjugated estrogen were administered for a three-month period to 23 premenopausal and postmenopausal inpatient women. Placebos were administered for a comparable period to 17 similar patients. The posttreatment Hamilton ratings of depression were significantly reduced in the estrogen-treated group, but not in the placebo group. Possible physiological mechanisms are discussed. The risk-benefit ratio for estrogen therapy of depression in these patients was judged to be favorable. However, periodic endometrial biopsies are required to monitor the endometrial response of women receiving high doses of estrogens.", "contents": "Estrogen therapy for severe persistent depressions in women. Positive results are reported from a double-blind study of estrogen therapy administered to severely depressed, inpatient women who had failed to respond to various conventional treatments of depression. Large doses of oral conjugated estrogen were administered for a three-month period to 23 premenopausal and postmenopausal inpatient women. Placebos were administered for a comparable period to 17 similar patients. The posttreatment Hamilton ratings of depression were significantly reduced in the estrogen-treated group, but not in the placebo group. Possible physiological mechanisms are discussed. The risk-benefit ratio for estrogen therapy of depression in these patients was judged to be favorable. However, periodic endometrial biopsies are required to monitor the endometrial response of women receiving high doses of estrogens."}
{"id": "PMID:219803", "title": "Cytochemical studies of ameloblasts and the surface layer of enamel of the rat incisor at the maturation stage.", "content": "In order to elucidate the cytochemical properties of the membranous structure between enamel and ameloblasts of the rat incisor at the maturation stage, chromic phosphotungstic acid (Cr-PTA) and periodic acid-silver methenamine (PA-silver) techniques for electron microscopy were employed in combination with a digestion test with hyaluronidase, neuraminidase, collagenase or trypsin. Also, acid phosphatase activity of ameloblasts at the maturation stage was examined with a modified GOMORI's metal salt method. An intensely Cr-PTA reactive band approximately 0.1 micron thick appeared along the surface layer of enamel at the transitional stage, and at the very beginning of the maturation stage another intensely Cr-PTA reactive band which was seen by uran-lead stain to be a delicate electron-dense membranous structure appeared as well between enamel and ameloblasts. A lot of cytoplasmic small vesicles or tubular structures, both intensely reactive to Cr-PTA, were observed near the apical membranes of the overlying ameloblasts indicating that those organelles must have been responsible for the secretion of the latter band. Acid phosphatase activity was clearly demonstrated at Cr-PTA reactive large vesicles in the cytoplasm of those cells. The PA-silver staining technique manifested a band heavily deposited with silver grains along the surface layer of enamel, i.e., where the former band existed, but showed no particular reaction at the latter, the band-like layer between enamel and ameloblasts. Hyaluronidase or neuraminidase treatment remarkably decreased the Cr-PTA reaction of the latter band. Trypsin or collagenase treatment, on the other hand, not only eliminated the Cr-PTA reaction but digested the band itself. These results suggest that the membranous structure between enamel and ameloblasts of a rat incisor is not so-called enamel cuticle but a basal lamina produced by overlying ameloblasts and that the basal lamina contains collagenous components even though it lies on enamel.", "contents": "Cytochemical studies of ameloblasts and the surface layer of enamel of the rat incisor at the maturation stage. In order to elucidate the cytochemical properties of the membranous structure between enamel and ameloblasts of the rat incisor at the maturation stage, chromic phosphotungstic acid (Cr-PTA) and periodic acid-silver methenamine (PA-silver) techniques for electron microscopy were employed in combination with a digestion test with hyaluronidase, neuraminidase, collagenase or trypsin. Also, acid phosphatase activity of ameloblasts at the maturation stage was examined with a modified GOMORI's metal salt method. An intensely Cr-PTA reactive band approximately 0.1 micron thick appeared along the surface layer of enamel at the transitional stage, and at the very beginning of the maturation stage another intensely Cr-PTA reactive band which was seen by uran-lead stain to be a delicate electron-dense membranous structure appeared as well between enamel and ameloblasts. A lot of cytoplasmic small vesicles or tubular structures, both intensely reactive to Cr-PTA, were observed near the apical membranes of the overlying ameloblasts indicating that those organelles must have been responsible for the secretion of the latter band. Acid phosphatase activity was clearly demonstrated at Cr-PTA reactive large vesicles in the cytoplasm of those cells. The PA-silver staining technique manifested a band heavily deposited with silver grains along the surface layer of enamel, i.e., where the former band existed, but showed no particular reaction at the latter, the band-like layer between enamel and ameloblasts. Hyaluronidase or neuraminidase treatment remarkably decreased the Cr-PTA reaction of the latter band. Trypsin or collagenase treatment, on the other hand, not only eliminated the Cr-PTA reaction but digested the band itself. These results suggest that the membranous structure between enamel and ameloblasts of a rat incisor is not so-called enamel cuticle but a basal lamina produced by overlying ameloblasts and that the basal lamina contains collagenous components even though it lies on enamel."}
{"id": "PMID:219804", "title": "Anti-Gm and anti-Inv antibodies in children during the course of clinical infectious mononucleosis syndrome.", "content": "Forty-eight children with the symptoms of infectious mononucleosis were examined. In six of then anti-Gm(1) antibodies were discovered, in two anti-Gm (21), in one child anti-Inv (1).", "contents": "Anti-Gm and anti-Inv antibodies in children during the course of clinical infectious mononucleosis syndrome. Forty-eight children with the symptoms of infectious mononucleosis were examined. In six of then anti-Gm(1) antibodies were discovered, in two anti-Gm (21), in one child anti-Inv (1)."}
{"id": "PMID:219805", "title": "Studies on cyclic AMP-cyclic GMP cooperation and on the influence of acetylcholine, adrenaline and thiols in lymphocyte reactivity.", "content": "In rat's lymph node lymphocytes, maximal stimulation of the response after suboptimal doses of PHA (1/2 of the optimal dose), measured by the incorporation of 3H-thymidine, after 10(-6) M acetylcholine and after 10 min interval between PHA and acetylcholine application was obtained. In these experiments inhibition of acetylcholine action by its muscarainic antagonists was not observed. It was shown that exogeneous cAMP as well as other factors, which increase cAMP level in lymphocytes had opposite effects to those, which could be caused by increasing of cGMP. Acetylcholine in optimal concentration (10(-6) M) as well as thiols, did not increase the level of endogeneous cAMP in rat lymphocytes.", "contents": "Studies on cyclic AMP-cyclic GMP cooperation and on the influence of acetylcholine, adrenaline and thiols in lymphocyte reactivity. In rat's lymph node lymphocytes, maximal stimulation of the response after suboptimal doses of PHA (1/2 of the optimal dose), measured by the incorporation of 3H-thymidine, after 10(-6) M acetylcholine and after 10 min interval between PHA and acetylcholine application was obtained. In these experiments inhibition of acetylcholine action by its muscarainic antagonists was not observed. It was shown that exogeneous cAMP as well as other factors, which increase cAMP level in lymphocytes had opposite effects to those, which could be caused by increasing of cGMP. Acetylcholine in optimal concentration (10(-6) M) as well as thiols, did not increase the level of endogeneous cAMP in rat lymphocytes."}
{"id": "PMID:219806", "title": "Heterospecific activity of rat interferon.", "content": "In the experiments performed in vitro and in vivo it has been found that the rat and rat embryo fibroblasts cultured in vitro after the induction with virus produce interferon which displays the antiviral activity not only in the homologous cells but also in the heterologous ones. When analysed by chromatography on Sephadex G-100 it was shown that the rat serum contains two interferon populations differing in the molecular weight and both active in the homologous and heterologous cells. The interferon with the heterospecific activity has been used in the experimental therapy of mice infected with Encephalomyocarditis Virus (EMC), Vesicular Stomatitis Virus (VSV) and Influenza Virus, and was found to be effective.", "contents": "Heterospecific activity of rat interferon. In the experiments performed in vitro and in vivo it has been found that the rat and rat embryo fibroblasts cultured in vitro after the induction with virus produce interferon which displays the antiviral activity not only in the homologous cells but also in the heterologous ones. When analysed by chromatography on Sephadex G-100 it was shown that the rat serum contains two interferon populations differing in the molecular weight and both active in the homologous and heterologous cells. The interferon with the heterospecific activity has been used in the experimental therapy of mice infected with Encephalomyocarditis Virus (EMC), Vesicular Stomatitis Virus (VSV) and Influenza Virus, and was found to be effective."}
{"id": "PMID:219807", "title": "Studies on the mode of action of IME--an inhibitor of interferon activity from mouse embryo tissues.", "content": "IME--inhibitor of interferon activity from mouse embryo tissues does not inactive interferon by direct contact; it does not inhibit the production of interferon and it does not affect the replication of challenge virus. IME shows no species-specific activity since it exhibits anti-interferon action not only in homologous interferon system but also in the heterologous rat, chick and human interferon systems. The interferon-induced antiviral state as well as the efficient cell's metabolism appear to be necessary for the expression of activity of IME.", "contents": "Studies on the mode of action of IME--an inhibitor of interferon activity from mouse embryo tissues. IME--inhibitor of interferon activity from mouse embryo tissues does not inactive interferon by direct contact; it does not inhibit the production of interferon and it does not affect the replication of challenge virus. IME shows no species-specific activity since it exhibits anti-interferon action not only in homologous interferon system but also in the heterologous rat, chick and human interferon systems. The interferon-induced antiviral state as well as the efficient cell's metabolism appear to be necessary for the expression of activity of IME."}
{"id": "PMID:219808", "title": "Studies of RNA isolated from Piptoporus betulinus as interferon inducer.", "content": "Crude RNA isolated from Piptoporus betulinus and two fractions of it obtained after the chromatography contain single-stranded RNA. The crude RNA, but not its chromatographic fractions, are resistant to the pancreatic RNA-ase. The crude preparation of RNA from P. betulinus contains beside ribose, considerable amounts of glucose, galactose and mannose. The crude RNA from P. betulinus induces in the human fibroblasts interferon with specific activity of 400 units per mg of protein.", "contents": "Studies of RNA isolated from Piptoporus betulinus as interferon inducer. Crude RNA isolated from Piptoporus betulinus and two fractions of it obtained after the chromatography contain single-stranded RNA. The crude RNA, but not its chromatographic fractions, are resistant to the pancreatic RNA-ase. The crude preparation of RNA from P. betulinus contains beside ribose, considerable amounts of glucose, galactose and mannose. The crude RNA from P. betulinus induces in the human fibroblasts interferon with specific activity of 400 units per mg of protein."}
{"id": "PMID:219809", "title": "Application of antisera to interferon in studying oncogenic viruses.", "content": "Susceptibility of BALB/c mice to infection with Moloney sarcoma virus (MSV) and to Herpes simplex virus type 2 (HSV-2) was considerably increased by administration of sheep anti-mouse interferon (anti-IF) serum. The regression of the MSV-induced tumors was inhibited when the weanling (three-to-four-week-old) mice were injected with the anti-IF serum. Using the anti-IF serum it has been found that the antagonism between HSV-2 and Rauscher leukemia virus in the mouse is not mediated by interferon. It is suggested that interferon is an important factor controlling growth of virus and/or virus induced tumor cells in the mouse before it develops a strong immunological response.", "contents": "Application of antisera to interferon in studying oncogenic viruses. Susceptibility of BALB/c mice to infection with Moloney sarcoma virus (MSV) and to Herpes simplex virus type 2 (HSV-2) was considerably increased by administration of sheep anti-mouse interferon (anti-IF) serum. The regression of the MSV-induced tumors was inhibited when the weanling (three-to-four-week-old) mice were injected with the anti-IF serum. Using the anti-IF serum it has been found that the antagonism between HSV-2 and Rauscher leukemia virus in the mouse is not mediated by interferon. It is suggested that interferon is an important factor controlling growth of virus and/or virus induced tumor cells in the mouse before it develops a strong immunological response."}
{"id": "PMID:219810", "title": "Immunological experimental arthritis in pigs. I. Propagation dynamics of the attenuated strain of Aujeszky's disease virus in the pig organism and the humoral immunity formation.", "content": "Studies on the propagation dynamics of Aujeszky's disease virus and the formation of general and local joint immunity were to provide information explaining the mechanism of experimental rheumatoid arthritis in animals. It was shown that: Aujeszky's disease virus administered intramuscularly caused viremy on 3-4th day after its application and disappeared from the blood circulation on 5-6th day, introduced into the pig ankle joint, the virus was eliminated from the articular fluid two hours after injection, but it appeared again 3-7 days later probably due to the propagation in the cells of the synovial membrane, and that first parenteral administration of the virus induced the formation of neutralizing antibodies in low titer (5-10 units); application of the virus for the second time brought about a considerable increase of antibodies titer within 40-80 units.", "contents": "Immunological experimental arthritis in pigs. I. Propagation dynamics of the attenuated strain of Aujeszky's disease virus in the pig organism and the humoral immunity formation. Studies on the propagation dynamics of Aujeszky's disease virus and the formation of general and local joint immunity were to provide information explaining the mechanism of experimental rheumatoid arthritis in animals. It was shown that: Aujeszky's disease virus administered intramuscularly caused viremy on 3-4th day after its application and disappeared from the blood circulation on 5-6th day, introduced into the pig ankle joint, the virus was eliminated from the articular fluid two hours after injection, but it appeared again 3-7 days later probably due to the propagation in the cells of the synovial membrane, and that first parenteral administration of the virus induced the formation of neutralizing antibodies in low titer (5-10 units); application of the virus for the second time brought about a considerable increase of antibodies titer within 40-80 units."}
{"id": "PMID:219811", "title": "Immunological experimental arthritis in pigs. II. The level of complement in the pigs immunized with the Erysipelothrix rhusiopathiae and virus of Aujeszky's disease.", "content": "The level of complement was studied in 3 groups of pigs. One group was immunized with Erysipelothrix rhusiopathiae and two remaining groups with virus of Aujeszky's disease. The lowest titers, irrespective of the starting level were shown to exist in all the studied groups in the third week after the last dose of the virus.", "contents": "Immunological experimental arthritis in pigs. II. The level of complement in the pigs immunized with the Erysipelothrix rhusiopathiae and virus of Aujeszky's disease. The level of complement was studied in 3 groups of pigs. One group was immunized with Erysipelothrix rhusiopathiae and two remaining groups with virus of Aujeszky's disease. The lowest titers, irrespective of the starting level were shown to exist in all the studied groups in the third week after the last dose of the virus."}
{"id": "PMID:219812", "title": "Immunological experimental arthritis in pigs. III. Inflammatory reactions in the brain of pigs immunized with the attenuated virus of Aujeszky's disease.", "content": "Histopathological brains and spinal cords of pigs were examined at different times of immunization with the virus of Aujeszky's disease (AD). Temporary inflammatory reaction was found to have the features of non-suppurative disseminated inflammation in the second week after the second virus dose had been given. Perivascular and subependymal lymphocytic infiltrations were observed and the focal multiplication of microglia.", "contents": "Immunological experimental arthritis in pigs. III. Inflammatory reactions in the brain of pigs immunized with the attenuated virus of Aujeszky's disease. Histopathological brains and spinal cords of pigs were examined at different times of immunization with the virus of Aujeszky's disease (AD). Temporary inflammatory reaction was found to have the features of non-suppurative disseminated inflammation in the second week after the second virus dose had been given. Perivascular and subependymal lymphocytic infiltrations were observed and the focal multiplication of microglia."}
{"id": "PMID:219813", "title": "Immunological experimental arthritis in pigs. IV. Reaction of the synovial membrane of the non-immunized and immunized pigs after intraarticular administration of the virus of Aujeszky's disease.", "content": "7 days after intramuscular administration of the attenuated virus of Aujeszky's disease, strain TK 300 L, it was found: in non-immunized animals--immunological arthritis with fibrinoid necrosis and abundant infiltrations from lymphoid cells; in animals of low antibodies titer--only few infiltrations from lymphoid and plasmic cells round the sub-synovial vessels; in animals of high antibodies titer--vast areas of fibrinoid necrosis, abundant infiltrations from lymphoid cells and presence of gigantic cells.", "contents": "Immunological experimental arthritis in pigs. IV. Reaction of the synovial membrane of the non-immunized and immunized pigs after intraarticular administration of the virus of Aujeszky's disease. 7 days after intramuscular administration of the attenuated virus of Aujeszky's disease, strain TK 300 L, it was found: in non-immunized animals--immunological arthritis with fibrinoid necrosis and abundant infiltrations from lymphoid cells; in animals of low antibodies titer--only few infiltrations from lymphoid and plasmic cells round the sub-synovial vessels; in animals of high antibodies titer--vast areas of fibrinoid necrosis, abundant infiltrations from lymphoid cells and presence of gigantic cells."}
{"id": "PMID:219814", "title": "Immunological experimental arthritis in pigs. V. Reaction of the synovial membrane in the pigs non-immunized and immunized with the virus of Aujeszky's disease after the intraarticular administration of the immunological complexes.", "content": "Immunized animals were given intraarticular complexes formed in vitro from the autologous serum and virus AD. 7 days after complex administration with excess of the virus, weak inflammatory reactions of the immunological type were noted. After neutral complex administration virulent immunological inflammation of the synovial membrane took place. The histological picture resembled rheumatoid arthritis in the man and the changes obtained after the virus administration to the joints with a high level of antibodies. Administration of complexes and homological serum alone to the joints of the nonimmunized animals caused the occurrence of superficial focuses of fibrinoid necrosis, but there was a lack of cellular reactions.", "contents": "Immunological experimental arthritis in pigs. V. Reaction of the synovial membrane in the pigs non-immunized and immunized with the virus of Aujeszky's disease after the intraarticular administration of the immunological complexes. Immunized animals were given intraarticular complexes formed in vitro from the autologous serum and virus AD. 7 days after complex administration with excess of the virus, weak inflammatory reactions of the immunological type were noted. After neutral complex administration virulent immunological inflammation of the synovial membrane took place. The histological picture resembled rheumatoid arthritis in the man and the changes obtained after the virus administration to the joints with a high level of antibodies. Administration of complexes and homological serum alone to the joints of the nonimmunized animals caused the occurrence of superficial focuses of fibrinoid necrosis, but there was a lack of cellular reactions."}
{"id": "PMID:219815", "title": "Studies on cell surface antigens of mouse leukemic and normal lymphocytes. II. Relationships between mammary leukemia, gross virus related and major histocompatibility antigens on L1210 leukemic lymphocytes.", "content": "The presence of ML antigen on leukemia L1210 cells was confirmed by different procedures. In addition, by applying appropriate absorptions and blocking techniques combined with ferritin labelled antibodies in electron microscopy (EM), the independent localization of ML antigen and murine leukemia virus Gross (MuLV-Gross) cellular antigen on L1210 cells was demonstrated. The ferritin labeled antigenic sites appeared to be free from budding viral particles. In further studies the 3M KCI extracts of L1210 leukemia cells purified by polyacrylamide gel electrophoresis (PAGE) and the antigenic material from leukemia L1210 cells purified by affinity chromatography were characterized. Their identity was verified by anti ML-sera. Using the modified lyso-strip method, the presence of ML antigen and H-2K and H-2D gene products on independent molecules on the surface of L1210 cells was shown. In addition, in preparative polyacrylamide gel electrophoresis (PAGE) of 3M KCL extracts of L1210 cells, ML and H-2d antigenic products were found in separate fractions.", "contents": "Studies on cell surface antigens of mouse leukemic and normal lymphocytes. II. Relationships between mammary leukemia, gross virus related and major histocompatibility antigens on L1210 leukemic lymphocytes. The presence of ML antigen on leukemia L1210 cells was confirmed by different procedures. In addition, by applying appropriate absorptions and blocking techniques combined with ferritin labelled antibodies in electron microscopy (EM), the independent localization of ML antigen and murine leukemia virus Gross (MuLV-Gross) cellular antigen on L1210 cells was demonstrated. The ferritin labeled antigenic sites appeared to be free from budding viral particles. In further studies the 3M KCI extracts of L1210 leukemia cells purified by polyacrylamide gel electrophoresis (PAGE) and the antigenic material from leukemia L1210 cells purified by affinity chromatography were characterized. Their identity was verified by anti ML-sera. Using the modified lyso-strip method, the presence of ML antigen and H-2K and H-2D gene products on independent molecules on the surface of L1210 cells was shown. In addition, in preparative polyacrylamide gel electrophoresis (PAGE) of 3M KCL extracts of L1210 cells, ML and H-2d antigenic products were found in separate fractions."}
{"id": "PMID:219816", "title": "Intestinal strangulation in germfree and monocontaminated dogs.", "content": "Earlier studies in the germfree rat demonstrated that the common intestinal bacteria vary greatly in their ability to cause death after intestinal strangulation. Some of these experiments were repeated in adult, germfree and monocontaminated beagles. Neither short closed-loop hemorrhagic nor long closed-loop ischemic strangulation killed the germfree dog. Either procedure rapidly killed the dog with a conventional bacterial flora or a dog monocontaminated with Clostridium perfringens. The dogs monocontaminated with Bacteroides fragilis died after several days, whereas Escherichia coli killed only one of three animals. These experiments demonstrate the usefulness of the germfree dog as a unique research subject, confirm our earlier studies on intestinal strangulation in germfree rats, and further emphasize the differing lethal potentials of the intestinal bacteria in intestinal strangulation.", "contents": "Intestinal strangulation in germfree and monocontaminated dogs. Earlier studies in the germfree rat demonstrated that the common intestinal bacteria vary greatly in their ability to cause death after intestinal strangulation. Some of these experiments were repeated in adult, germfree and monocontaminated beagles. Neither short closed-loop hemorrhagic nor long closed-loop ischemic strangulation killed the germfree dog. Either procedure rapidly killed the dog with a conventional bacterial flora or a dog monocontaminated with Clostridium perfringens. The dogs monocontaminated with Bacteroides fragilis died after several days, whereas Escherichia coli killed only one of three animals. These experiments demonstrate the usefulness of the germfree dog as a unique research subject, confirm our earlier studies on intestinal strangulation in germfree rats, and further emphasize the differing lethal potentials of the intestinal bacteria in intestinal strangulation."}
{"id": "PMID:219817", "title": "Lewy bodies in the presence of Alzheimer's disease.", "content": "Large numbers of Lewy bodies in the substantia nigra were found in a case of Alzheimer's disease. Parkinsonian symptoms were not recognized. The patient appears to be an example of an association recognized by Woodard but not yet understood. The case is discussed in the context of reported relationships between Parkinson's disease or \"Lewy body disease\" and dementia, on the one hand, and reports linking various forms of psychoses with an unusually high incidence of Lewy bodies, on the other.", "contents": "Lewy bodies in the presence of Alzheimer's disease. Large numbers of Lewy bodies in the substantia nigra were found in a case of Alzheimer's disease. Parkinsonian symptoms were not recognized. The patient appears to be an example of an association recognized by Woodard but not yet understood. The case is discussed in the context of reported relationships between Parkinson's disease or \"Lewy body disease\" and dementia, on the one hand, and reports linking various forms of psychoses with an unusually high incidence of Lewy bodies, on the other."}
{"id": "PMID:219819", "title": "Facial nerve in recurrent benign pleomorphic adenoma.", "content": "Improvements in the treatment of benign and malignant tumors in the parotid gland have substantially reduced the incidence of recurrence. This has come about primarily be the abandonment of the enucleation techniques and the development of lateral lobectomy operation. The recurrence rate for benign mixed tumor in the parotid gland is variously reported in the ranges of 0.5% to 10%. Because the benign mixed tumor comprises approximately 65% of the tumors in this gland, this complication assumes an important and specific role. A review of this problem establishes the principles of management, extending from simple reexcision through total parotidectomy with preservation of the facial nerve, and radical parotidectomy with resection of the facial nerve and immediate nerve grafting.", "contents": "Facial nerve in recurrent benign pleomorphic adenoma. Improvements in the treatment of benign and malignant tumors in the parotid gland have substantially reduced the incidence of recurrence. This has come about primarily be the abandonment of the enucleation techniques and the development of lateral lobectomy operation. The recurrence rate for benign mixed tumor in the parotid gland is variously reported in the ranges of 0.5% to 10%. Because the benign mixed tumor comprises approximately 65% of the tumors in this gland, this complication assumes an important and specific role. A review of this problem establishes the principles of management, extending from simple reexcision through total parotidectomy with preservation of the facial nerve, and radical parotidectomy with resection of the facial nerve and immediate nerve grafting."}
{"id": "PMID:219822", "title": "[Morphology of a malignant parotideal lymphoma with paraproteinaceous cytoplasmic inclusions (author's transl)].", "content": "A female patient presented with a lump in the right parotedeal region. A needle aspiration biopsy was performed which revealed numerous monomorphous atypical lymphoid cells with PAS-negative cytoplasmic inclusions. This raised the suspicion of malignancy. Therefore, the tumour was excised. Histologically, a nodular lymphoma of low grade of malignancy was diagnosed. The tumour contained many epithelioid histiocytes, sometimes with PAS-positive material. The case was difficult to classify after the Kiel-nomenclature, whilst classification on the basis of Rappaport's system was much easier.", "contents": "[Morphology of a malignant parotideal lymphoma with paraproteinaceous cytoplasmic inclusions (author's transl)]. A female patient presented with a lump in the right parotedeal region. A needle aspiration biopsy was performed which revealed numerous monomorphous atypical lymphoid cells with PAS-negative cytoplasmic inclusions. This raised the suspicion of malignancy. Therefore, the tumour was excised. Histologically, a nodular lymphoma of low grade of malignancy was diagnosed. The tumour contained many epithelioid histiocytes, sometimes with PAS-positive material. The case was difficult to classify after the Kiel-nomenclature, whilst classification on the basis of Rappaport's system was much easier."}
{"id": "PMID:219823", "title": "Idiopathic facial palsy. Viral, hereditary, or both?", "content": "Two cases of acute peripheral facial paralysis occurring in two siblings in a family of six members, who all developed influenza-like symptoms, are reported. Both patients with facial paralysis, as well as two other members of the family had elevated titers against herpes simplex virus, even though it was not possible to demonstrate any raise in titers between the acute and convalescent phase. The \"epidemic\" occurrence is from a statistical point of view more than just a coincidence, and it is concluded that these findings support the hypothesis that Bell's palsy may be caused by reactivation of herpes simplex virus, probably facilitated by some hereditary component. The authors suggest that a combination of infectious (most likely viral) and hereditary factors may be etiologically important for the occurrence of acute peripheral facial paralysis.", "contents": "Idiopathic facial palsy. Viral, hereditary, or both? Two cases of acute peripheral facial paralysis occurring in two siblings in a family of six members, who all developed influenza-like symptoms, are reported. Both patients with facial paralysis, as well as two other members of the family had elevated titers against herpes simplex virus, even though it was not possible to demonstrate any raise in titers between the acute and convalescent phase. The \"epidemic\" occurrence is from a statistical point of view more than just a coincidence, and it is concluded that these findings support the hypothesis that Bell's palsy may be caused by reactivation of herpes simplex virus, probably facilitated by some hereditary component. The authors suggest that a combination of infectious (most likely viral) and hereditary factors may be etiologically important for the occurrence of acute peripheral facial paralysis."}
{"id": "PMID:219828", "title": "Infectious bursal disease virus infection attempts in turkeys and Coturnix quail.", "content": "Attempts failed to infect Coturnix quail with infectious bursal disease (IBD) virus by exposure at 7, 14, 21, and 31 days old. There were no clinical signs or gross and microscopic changes in the bursa of Fabricius, and serologic tests and virus isolation attempts from cloacal swabs were negative. Turkeys of two breeds exposed to IBD virus at 6 or 8 weeks old showed no clinical signs or lesions in the bursa of Fabricius, and the virus could not be isolated from cloacal swabs. They did respond serologically, however, by developing both precipitin and virus-neutralizing antibodies.", "contents": "Infectious bursal disease virus infection attempts in turkeys and Coturnix quail. Attempts failed to infect Coturnix quail with infectious bursal disease (IBD) virus by exposure at 7, 14, 21, and 31 days old. There were no clinical signs or gross and microscopic changes in the bursa of Fabricius, and serologic tests and virus isolation attempts from cloacal swabs were negative. Turkeys of two breeds exposed to IBD virus at 6 or 8 weeks old showed no clinical signs or lesions in the bursa of Fabricius, and the virus could not be isolated from cloacal swabs. They did respond serologically, however, by developing both precipitin and virus-neutralizing antibodies."}
{"id": "PMID:219827", "title": "Virus-neutralization versus agar-gel precipitin tests for detecting serological response to infectious bursal disease virus.", "content": "The virus-neutralization (VN) test was found much more sensitive than the agar-gel precipitin (AGP) test for detecting prior exposure to infectious bursal disease (IBD). Many sera that were negative in the AGP test were found to have VN antibodies, and virtually all sera in a commercial flock were free of precipitin but had VN titers. VN titers varied widely on a flock basis, and revaccination of an 8-month-old flock through the drinking water did not alter the antibody titers. Inoculation of maternally immune chicks at 7 days of age with IBD virus resulted in a good serologic response by both the AGP and VN tests.", "contents": "Virus-neutralization versus agar-gel precipitin tests for detecting serological response to infectious bursal disease virus. The virus-neutralization (VN) test was found much more sensitive than the agar-gel precipitin (AGP) test for detecting prior exposure to infectious bursal disease (IBD). Many sera that were negative in the AGP test were found to have VN antibodies, and virtually all sera in a commercial flock were free of precipitin but had VN titers. VN titers varied widely on a flock basis, and revaccination of an 8-month-old flock through the drinking water did not alter the antibody titers. Inoculation of maternally immune chicks at 7 days of age with IBD virus resulted in a good serologic response by both the AGP and VN tests."}
{"id": "PMID:219830", "title": "Preparation of inactivated oil-emulsion vaccines with avian viral or Mycoplasma antigens.", "content": "The influence of the composition of water-in-oil emulsions on their physical characteristics was determined by preparing experimental emulsions with various water-to-oil ratios and various emulsifiers. Emulsions containing Tween 80 in the aqueous phase and Arlacel A or Arlacel 80 in the oil phase were lower in viscosity than emulsions containing only an oil-phase emulsifier. Viscosity decreased as the concentration of oil increased. Oil-emulsion vaccines prepared with aqueous- and oil-phase emulsifiers had low viscosity, were stable for more than 12 weeks at 37 C, and induced a marked primary antibody response in chickens.", "contents": "Preparation of inactivated oil-emulsion vaccines with avian viral or Mycoplasma antigens. The influence of the composition of water-in-oil emulsions on their physical characteristics was determined by preparing experimental emulsions with various water-to-oil ratios and various emulsifiers. Emulsions containing Tween 80 in the aqueous phase and Arlacel A or Arlacel 80 in the oil phase were lower in viscosity than emulsions containing only an oil-phase emulsifier. Viscosity decreased as the concentration of oil increased. Oil-emulsion vaccines prepared with aqueous- and oil-phase emulsifiers had low viscosity, were stable for more than 12 weeks at 37 C, and induced a marked primary antibody response in chickens."}
{"id": "PMID:219831", "title": "Experimental induction of hemorrhagic-aplastic anemia in chickens. I. Etiology.", "content": "Exposure to infectious bursal disease virus (IBDV) at 1 day old followed by inclusion body hepatitis virus (IBHV) inoculation at 36 days produced typical lesions of hemorrhagic-aplastic anemia syndrome (HAS). The lesions included severe anemia, widespread hemorrhages, and dermatitis. HAS could not be induced in the first 4 weeks of life in chickens inoculated at one day old with IBHV alone or in combination with IBDV. It was concluded that the immunosuppressive effects of IBDV failed to alter the pathogenicity of IBHV in chicks less than 4 weeks old. This resistance was considered to be age-related. Subcutaneous inoculation of day-old chicks with IBDV produced a more severe infection than did oral exposure. Serial passage of IBHV in day-old chicks had no significant effect on the viral pathogenicity.", "contents": "Experimental induction of hemorrhagic-aplastic anemia in chickens. I. Etiology. Exposure to infectious bursal disease virus (IBDV) at 1 day old followed by inclusion body hepatitis virus (IBHV) inoculation at 36 days produced typical lesions of hemorrhagic-aplastic anemia syndrome (HAS). The lesions included severe anemia, widespread hemorrhages, and dermatitis. HAS could not be induced in the first 4 weeks of life in chickens inoculated at one day old with IBHV alone or in combination with IBDV. It was concluded that the immunosuppressive effects of IBDV failed to alter the pathogenicity of IBHV in chicks less than 4 weeks old. This resistance was considered to be age-related. Subcutaneous inoculation of day-old chicks with IBDV produced a more severe infection than did oral exposure. Serial passage of IBHV in day-old chicks had no significant effect on the viral pathogenicity."}
{"id": "PMID:219829", "title": "Comparative pathogenicity of six avian adenovirus isolants in the liver.", "content": "The comparative pathogenicity of six avian adenovirus isolants for chickens was determined. The most virulent isolant was DPI-1, causing focal to massive hepatic necrosis with hemorrhage, while Tipton (Conn), Tipton (Purdue), GAL-1, and DPI-2 isolants were considered less pathogenic and produced only mild focal hepatic necrosis. The Indiana-C isolant was the least pathogenic and failed to produce any significant hepatic lesions. Intranuclear inclusions were observed in hepatocytes of all but the Indiana-C inoculated chickens on the third day postinoculation (PI), disappearing by the seventh day PI.", "contents": "Comparative pathogenicity of six avian adenovirus isolants in the liver. The comparative pathogenicity of six avian adenovirus isolants for chickens was determined. The most virulent isolant was DPI-1, causing focal to massive hepatic necrosis with hemorrhage, while Tipton (Conn), Tipton (Purdue), GAL-1, and DPI-2 isolants were considered less pathogenic and produced only mild focal hepatic necrosis. The Indiana-C isolant was the least pathogenic and failed to produce any significant hepatic lesions. Intranuclear inclusions were observed in hepatocytes of all but the Indiana-C inoculated chickens on the third day postinoculation (PI), disappearing by the seventh day PI."}
{"id": "PMID:219833", "title": "In vitro inactivation of cell-free Marek's disease herpesvirus by immune peripheral blood lymphocytes.", "content": "The effect of peripheral blood lymphocytes (PBL) on cell-free Marek's disease virus (MDV) was studied in vitro in PBL from intact or embryonal bursectomized (Bx) chicks infected with the apathogenic SB-1 isolate of MDV. The PBL were harvested purified and were mixed, 200 or 2,000 to 1, with cell-free GA-5 of MDV. Virus survival was assayed after incubation for 1 hour at 36 C by the standard assay for cell-free MDV. PBL from intact but not Bx chickens were able to inactivate virus. When the effective suspension of PBL was depleted of macrophages, inactivation no longer occurred, suggesting that it resulted from cooperation between macrophages and B-cells.", "contents": "In vitro inactivation of cell-free Marek's disease herpesvirus by immune peripheral blood lymphocytes. The effect of peripheral blood lymphocytes (PBL) on cell-free Marek's disease virus (MDV) was studied in vitro in PBL from intact or embryonal bursectomized (Bx) chicks infected with the apathogenic SB-1 isolate of MDV. The PBL were harvested purified and were mixed, 200 or 2,000 to 1, with cell-free GA-5 of MDV. Virus survival was assayed after incubation for 1 hour at 36 C by the standard assay for cell-free MDV. PBL from intact but not Bx chickens were able to inactivate virus. When the effective suspension of PBL was depleted of macrophages, inactivation no longer occurred, suggesting that it resulted from cooperation between macrophages and B-cells."}
{"id": "PMID:219832", "title": "Experimental induction of hemorrhagic-aplastic anemia in chickens. II. Serum protein changes.", "content": "The serologic response of chickens to infectious bursal disease virus (IBDV) and inclusion body hepatitis virus (IBHV) was analyzed. Inoculation at one day old with either IBDV or IBHV significantly (P less than 0.05) reduced levels of serum gamma-globulins at 4 weeks postinoculation. This response was not elicited by inoculation of IBDV together with IBHV. Birds with experimentally induced or naturally occurring hemorrhagic anemia syndrome (HAS) had serum proteins quantitatively and qualitatively changed from those of controls. Serum protein profiles did not coincide, however, in experimentally infected and naturally infected chickens. Among naturally infected chickens, those that were IBHV-positive upon culture had significantly (P less than 0.05) lower hematocrit values.", "contents": "Experimental induction of hemorrhagic-aplastic anemia in chickens. II. Serum protein changes. The serologic response of chickens to infectious bursal disease virus (IBDV) and inclusion body hepatitis virus (IBHV) was analyzed. Inoculation at one day old with either IBDV or IBHV significantly (P less than 0.05) reduced levels of serum gamma-globulins at 4 weeks postinoculation. This response was not elicited by inoculation of IBDV together with IBHV. Birds with experimentally induced or naturally occurring hemorrhagic anemia syndrome (HAS) had serum proteins quantitatively and qualitatively changed from those of controls. Serum protein profiles did not coincide, however, in experimentally infected and naturally infected chickens. Among naturally infected chickens, those that were IBHV-positive upon culture had significantly (P less than 0.05) lower hematocrit values."}
{"id": "PMID:219834", "title": "Airsacculitis induced in broilers with a combination of Mycoplasma gallinarum and respiratory viruses.", "content": "Mycoplasma gallinarum was isolated from tracheas and air-sac lesions from broilers in flocks having higher than normal condemnations due to airsacculitis. A representative M. gallinarum isolant, given by aerosol or by air-sac inoculation, produced air-sac lesions in young chickens when given in combination with a vaccine combining Newcastle disease and infectious bronchitis or with a field strain of infectious bronchitis virus.", "contents": "Airsacculitis induced in broilers with a combination of Mycoplasma gallinarum and respiratory viruses. Mycoplasma gallinarum was isolated from tracheas and air-sac lesions from broilers in flocks having higher than normal condemnations due to airsacculitis. A representative M. gallinarum isolant, given by aerosol or by air-sac inoculation, produced air-sac lesions in young chickens when given in combination with a vaccine combining Newcastle disease and infectious bronchitis or with a field strain of infectious bronchitis virus."}
{"id": "PMID:219835", "title": "Immune response and pathogenicity of different strains of infectious bursal disease virus applied as vaccines.", "content": "Eight strains of infectious bursal disease virus (IBDV) were characterized by the criteria of immunity and pathogenicity engendered in young chickens. Some strains have been used commercially, and the others are potential candidates for vaccines. They were administered by drinking water, eyedrop, vent drop, and subcutaneous and aerosol routes. The viruses varied widely in pathogenicity in terms of bursal damage, morbidity, and mortality. Immunity induced with different routes of administration also differed markedly when measured by challenge, virus serum-neutralizing antibody titers, and the agargel precipitin test. Maternally derived immunity interfered with stimulation of active immunity by some of the less pathogenic strains. The more virulent strains, however, were able to provide protection under similar circumstances, although bursal damage was frequently severe. Two strains proved relatively virulent by the criteria employed. Characteristics desirable for IBDV strains to be given as vaccines under field conditions to young chickens are discussed briefly.", "contents": "Immune response and pathogenicity of different strains of infectious bursal disease virus applied as vaccines. Eight strains of infectious bursal disease virus (IBDV) were characterized by the criteria of immunity and pathogenicity engendered in young chickens. Some strains have been used commercially, and the others are potential candidates for vaccines. They were administered by drinking water, eyedrop, vent drop, and subcutaneous and aerosol routes. The viruses varied widely in pathogenicity in terms of bursal damage, morbidity, and mortality. Immunity induced with different routes of administration also differed markedly when measured by challenge, virus serum-neutralizing antibody titers, and the agargel precipitin test. Maternally derived immunity interfered with stimulation of active immunity by some of the less pathogenic strains. The more virulent strains, however, were able to provide protection under similar circumstances, although bursal damage was frequently severe. Two strains proved relatively virulent by the criteria employed. Characteristics desirable for IBDV strains to be given as vaccines under field conditions to young chickens are discussed briefly."}
{"id": "PMID:219840", "title": "Studies on the polypeptides of poxvirus. I. Comparison of structural polypeptides in vaccina, cowpox and Shope fibroma viruses.", "content": "Radioactively labeled vaccinia, cowpox and Shope fibroma virions free from any detectable contamination with host cell protein, were dissociated into their constituent polypeptides, and these were then analyzed by SDS-polyacrylamide gel electrophoresis and autoradiography. The profiles of constituent polypeptide bands of four strains of vaccinia virus (IHD-W, IHD-J, Lister and DIs) were almost the same, except that a polypeptide of about 41,000 daltons was not detectable in the autoradiogram of strain IHD-W which has no hemagglutinin. The profile of polypeptide bands of cowpox virions was also almost the same as that of vaccinia virions, except for several polypeptides of about 40,000 to 50,000 daltons, but the profile of Shope fibroma virions differed considerably from that of vaccinia or cowpox virions.", "contents": "Studies on the polypeptides of poxvirus. I. Comparison of structural polypeptides in vaccina, cowpox and Shope fibroma viruses. Radioactively labeled vaccinia, cowpox and Shope fibroma virions free from any detectable contamination with host cell protein, were dissociated into their constituent polypeptides, and these were then analyzed by SDS-polyacrylamide gel electrophoresis and autoradiography. The profiles of constituent polypeptide bands of four strains of vaccinia virus (IHD-W, IHD-J, Lister and DIs) were almost the same, except that a polypeptide of about 41,000 daltons was not detectable in the autoradiogram of strain IHD-W which has no hemagglutinin. The profile of polypeptide bands of cowpox virions was also almost the same as that of vaccinia virions, except for several polypeptides of about 40,000 to 50,000 daltons, but the profile of Shope fibroma virions differed considerably from that of vaccinia or cowpox virions."}
{"id": "PMID:219836", "title": "Status of endogenous avian RNA tumor virus in Marek's disease lymphoblastoid cell lines and susceptibility of those lines to exogenous RNA tumor viruses.", "content": "Three lymphoblastoid cell lines from Marek's disease (MD) tumors, two MD virus (MDV) producer lines (MSB-1 and HPRS-1), and a nonproducer line (RPL-1) were studied for the expression of avian leukosis sarcoma (ALS) viruses. The MSB-1 line was free of all known endogenous expressions, including replicating virus (RAV-O), group-specific (gs) antigens, and chick helper factor (chf). The RPL-1 and HPRS-1 were positive for gs antigens and chf. The RPL-1 and MSB-1 lines showed no evidence of an exogenous DNA provirus by nucleic acid hybridization (HPRS-1 line was not tested for that DNA). All three lymphoblastoid cell lines were susceptible to exogenous infection with both sarcoma and leukosis viruses of subgroup A but varied in susceptibility to subgroups B and C. All were resistant to subgroups D and E.", "contents": "Status of endogenous avian RNA tumor virus in Marek's disease lymphoblastoid cell lines and susceptibility of those lines to exogenous RNA tumor viruses. Three lymphoblastoid cell lines from Marek's disease (MD) tumors, two MD virus (MDV) producer lines (MSB-1 and HPRS-1), and a nonproducer line (RPL-1) were studied for the expression of avian leukosis sarcoma (ALS) viruses. The MSB-1 line was free of all known endogenous expressions, including replicating virus (RAV-O), group-specific (gs) antigens, and chick helper factor (chf). The RPL-1 and HPRS-1 were positive for gs antigens and chf. The RPL-1 and MSB-1 lines showed no evidence of an exogenous DNA provirus by nucleic acid hybridization (HPRS-1 line was not tested for that DNA). All three lymphoblastoid cell lines were susceptible to exogenous infection with both sarcoma and leukosis viruses of subgroup A but varied in susceptibility to subgroups B and C. All were resistant to subgroups D and E."}
{"id": "PMID:219837", "title": "Avian adenoviruses--distribution of infection in commercial flocks of fowls in Argentina.", "content": "Group-specific avian adenovirus antibodies were surveyed in broiler, layer, and breeder chickens in three poultry-producing areas of Argentina: north, middle, and south. The method used was the agar double-immunodiffusion test. Of the flocks examined, 89% had antibodies to avian adenovirus, with the percentages higher in layers and breeders than in broiler chickens. A close relation was found between poorer hygienic condition and high adenovirus antibodies values.", "contents": "Avian adenoviruses--distribution of infection in commercial flocks of fowls in Argentina. Group-specific avian adenovirus antibodies were surveyed in broiler, layer, and breeder chickens in three poultry-producing areas of Argentina: north, middle, and south. The method used was the agar double-immunodiffusion test. Of the flocks examined, 89% had antibodies to avian adenovirus, with the percentages higher in layers and breeders than in broiler chickens. A close relation was found between poorer hygienic condition and high adenovirus antibodies values."}
{"id": "PMID:219843", "title": "Studies on the polypeptides of poxvirus. II. Comparison of virus-induced polypeptides in cells infected with vaccinia, cowpox and Shope fibroma viruses.", "content": "Virus-induced polypeptides in cells infected with vaccinia, cowpox and Shope fibroma viruses were examined by SDS-polyacrylamide gel electrophoresis followed by autoradiography. At least 42 vaccinia virus-induced polypeptides were identified among the polypeptides of cells pulse-labeled with [35S]-methionine and/or of fractionated cells labeled with [14C]-leucine for 24 hr. They consisted of 15 polypeptides (early polypeptides) which were synthesized even in the presence of cytosine-1-beta-D-arabinofuranosyl-HCl, and 27 polypeptides (late polypeptides) which were synthesized only in the absence of cytosine-1-beta-D-arabinofuranosyl-HCl. By the same procedure at least 40 cowpox virus-induced polypeptides (14 early polypeptides and 26 late polypeptides) and at least 31 Shope fibroma virus-induced polypeptides (13 early polypeptides and 18 late polypeptides) were identified. Comparative studies of virus-induced polypeptides on the basis of migration in SDS-polyacrylamide gel electrophoresis revealed that 11 polypeptides were early polypeptides common to both vaccinia and cowpox viruses; 21 were late polypeptides common to both vaccinia and cowpox viruses; 4 were early polypeptides common to both vaccinia and Shope fibroma viruses; 7 were late polypeptides common to both vaccinia and Shope fibroma viruses; 5 were early polypeptides common to both cowpox and Shope fibroma viruses; 9 were late polypeptides common to both cowpox and Shope fibroma viruses; 4 were early polypeptides common to all three viruses; and 7 were late polypeptides common to all three viruses.", "contents": "Studies on the polypeptides of poxvirus. II. Comparison of virus-induced polypeptides in cells infected with vaccinia, cowpox and Shope fibroma viruses. Virus-induced polypeptides in cells infected with vaccinia, cowpox and Shope fibroma viruses were examined by SDS-polyacrylamide gel electrophoresis followed by autoradiography. At least 42 vaccinia virus-induced polypeptides were identified among the polypeptides of cells pulse-labeled with [35S]-methionine and/or of fractionated cells labeled with [14C]-leucine for 24 hr. They consisted of 15 polypeptides (early polypeptides) which were synthesized even in the presence of cytosine-1-beta-D-arabinofuranosyl-HCl, and 27 polypeptides (late polypeptides) which were synthesized only in the absence of cytosine-1-beta-D-arabinofuranosyl-HCl. By the same procedure at least 40 cowpox virus-induced polypeptides (14 early polypeptides and 26 late polypeptides) and at least 31 Shope fibroma virus-induced polypeptides (13 early polypeptides and 18 late polypeptides) were identified. Comparative studies of virus-induced polypeptides on the basis of migration in SDS-polyacrylamide gel electrophoresis revealed that 11 polypeptides were early polypeptides common to both vaccinia and cowpox viruses; 21 were late polypeptides common to both vaccinia and cowpox viruses; 4 were early polypeptides common to both vaccinia and Shope fibroma viruses; 7 were late polypeptides common to both vaccinia and Shope fibroma viruses; 5 were early polypeptides common to both cowpox and Shope fibroma viruses; 9 were late polypeptides common to both cowpox and Shope fibroma viruses; 4 were early polypeptides common to all three viruses; and 7 were late polypeptides common to all three viruses."}
{"id": "PMID:219844", "title": "Field experiments on live attenuated Japanese encephalitis virus vaccine for swine.", "content": "The efficacy of a live attenuated Japanese encephalitis virus (JEV) vaccine was examined in swine under conditions where natural infection could occur. The pigs immunized with the vaccine produced antibodies within one week after vaccination, and the antibody was retained until the end of the experiment, i.e. 36 days. However, the antibody titers in this group were lower than that in control group naturally infected with JEV. No virus was isolated from the five vaccinated pigs, but virus was isolated from all four untreated control pigs after natural infection, i.e., viremia was detected in all these animals. The duration of viremia in control pigs varied from one to four days. From these findings, it is concluded that immunization of swine with live attentuated JEV vaccine is useful in control of Japanese encephalitis (JE) in humans and some susceptible domestic animals.", "contents": "Field experiments on live attenuated Japanese encephalitis virus vaccine for swine. The efficacy of a live attenuated Japanese encephalitis virus (JEV) vaccine was examined in swine under conditions where natural infection could occur. The pigs immunized with the vaccine produced antibodies within one week after vaccination, and the antibody was retained until the end of the experiment, i.e. 36 days. However, the antibody titers in this group were lower than that in control group naturally infected with JEV. No virus was isolated from the five vaccinated pigs, but virus was isolated from all four untreated control pigs after natural infection, i.e., viremia was detected in all these animals. The duration of viremia in control pigs varied from one to four days. From these findings, it is concluded that immunization of swine with live attentuated JEV vaccine is useful in control of Japanese encephalitis (JE) in humans and some susceptible domestic animals."}
{"id": "PMID:219845", "title": "Purification and characterization of subcomponent C1q of the first component of bovine complement.", "content": "Bovine C1q, a subcomponent of the first component of complement, was purified in high yield by a combination of euglobulin precipitation, and ion-exchange and molecularsieve chromatography on CM-cellulose and Ultrogel AcA 34. Approx. 12-16mg can be isolated from 1 litre of serum, representing a yield of 13-18%. The molecular weight of undissociated subcomponent C1q, as determined by equilibrium sedimentation, is 430000. On sodium dodecyl sulphate/polyacrylamide gels under non-reducing conditions, subcomponent C1q was shown to consist of two subunits of mol.wts. 69000 and 62000 in a molar ratio of 2:1. On reduction, the 69000-mol.wt. subunit gave chains of mol.wts. 30000 and 25000 in equimolar ratio, and the 62000-mol.wt. subunit decreased to 25000. The amino acid composition, with a high value for glycine, and the presence of hydroxyproline and hydroxylysine, suggests that there is a region of collagen-like sequence in the molecule. This is supported by the loss of haemolytic activity and the degradation of the polypeptide chains of subcomponent C1q when digested by collagenase. All of these molecular characteristics support the structure of six subunits, each containing three different polypeptide chains, with globular heads connected by collagen triple helices as proposed by Reid & Porter (1976) (Biochem. J.155, 19-23) for human subcomponent C1q. Subcomponent C1q contains approx. 9% carbohydrate; analysis of the degree of substitution of the hydroxylysine residues revealed that 91% are modified by the addition of the disaccharide unit Gal-Glc. Bovine subcomponent C1q generates full C1 haemolytic activity when assayed with human subcomponents C1r and C1s.", "contents": "Purification and characterization of subcomponent C1q of the first component of bovine complement. Bovine C1q, a subcomponent of the first component of complement, was purified in high yield by a combination of euglobulin precipitation, and ion-exchange and molecularsieve chromatography on CM-cellulose and Ultrogel AcA 34. Approx. 12-16mg can be isolated from 1 litre of serum, representing a yield of 13-18%. The molecular weight of undissociated subcomponent C1q, as determined by equilibrium sedimentation, is 430000. On sodium dodecyl sulphate/polyacrylamide gels under non-reducing conditions, subcomponent C1q was shown to consist of two subunits of mol.wts. 69000 and 62000 in a molar ratio of 2:1. On reduction, the 69000-mol.wt. subunit gave chains of mol.wts. 30000 and 25000 in equimolar ratio, and the 62000-mol.wt. subunit decreased to 25000. The amino acid composition, with a high value for glycine, and the presence of hydroxyproline and hydroxylysine, suggests that there is a region of collagen-like sequence in the molecule. This is supported by the loss of haemolytic activity and the degradation of the polypeptide chains of subcomponent C1q when digested by collagenase. All of these molecular characteristics support the structure of six subunits, each containing three different polypeptide chains, with globular heads connected by collagen triple helices as proposed by Reid & Porter (1976) (Biochem. J.155, 19-23) for human subcomponent C1q. Subcomponent C1q contains approx. 9% carbohydrate; analysis of the degree of substitution of the hydroxylysine residues revealed that 91% are modified by the addition of the disaccharide unit Gal-Glc. Bovine subcomponent C1q generates full C1 haemolytic activity when assayed with human subcomponents C1r and C1s."}
{"id": "PMID:219846", "title": "The assay of xylosyltransferase in cartilage extracts. A modified procedure for preparation of Smith-degraded proteoglycan.", "content": "A modification of the published method [Baker, Rod\u00e9n & Stoolmiller (1972) J. Biol. Chem. 247, 3838--3847] for preparation of Smith-degraded proteoglycan is described. The new method is based on the finding that most of the chondroitin sulphate is cleaved from proteoglycan core protein by periodate oxidation. The borohydride reduction procedure was modified because the periodate-oxidized core protein is extensively degraded under the highly alkaline conditions previously used. The new method involves the separation of periodate-oxidized core protein from chondroitin sulphate by gel filtration on Sepharose 6B, and the reduction of the former in H3BO3/NaBH4 at pH 8.5 to produce the reduced species. Smith-degraded proteoglycan prepared by this method exhibited high acceptor activity for xylosyltransferase from embryonic-chick cartilage and had an apparent Km of 160 microgram/ml or 45 micrometer on a serine basis. In this assay system an apparent Km of 19 micrometer was obtained for UDP-xylose. The intermediate products periodate-oxidized core protein and reduced proteoglycen were inactive as xylosyltransferase acceptor substrates.", "contents": "The assay of xylosyltransferase in cartilage extracts. A modified procedure for preparation of Smith-degraded proteoglycan. A modification of the published method [Baker, Rod\u00e9n & Stoolmiller (1972) J. Biol. Chem. 247, 3838--3847] for preparation of Smith-degraded proteoglycan is described. The new method is based on the finding that most of the chondroitin sulphate is cleaved from proteoglycan core protein by periodate oxidation. The borohydride reduction procedure was modified because the periodate-oxidized core protein is extensively degraded under the highly alkaline conditions previously used. The new method involves the separation of periodate-oxidized core protein from chondroitin sulphate by gel filtration on Sepharose 6B, and the reduction of the former in H3BO3/NaBH4 at pH 8.5 to produce the reduced species. Smith-degraded proteoglycan prepared by this method exhibited high acceptor activity for xylosyltransferase from embryonic-chick cartilage and had an apparent Km of 160 microgram/ml or 45 micrometer on a serine basis. In this assay system an apparent Km of 19 micrometer was obtained for UDP-xylose. The intermediate products periodate-oxidized core protein and reduced proteoglycen were inactive as xylosyltransferase acceptor substrates."}
{"id": "PMID:219847", "title": "Low-temperature kinetics of the reactions of fully reduced membrane-bound cytochrome oxidase with oxygen in the Soret, alpha and near-infrared regions.", "content": "The kinetics of the reaction of fully reduced membrane-bound cytochrome oxidase with O2 obtained in the Soret, alpha and near-i.r. regions were analysed, and the contributions of the three intermediates of the reaction [Clore & Chance (1978) Biochem. J. 173, 799--810] to seven wavelength pairs (430--463, 444--463, 590--630, 608--630, 740--940, 790--940 and 830--940 nm) were determined. The nature of the intermediates is discussed on the basis of the data in the present paper together with data in the literature from optical wavelength scanning, e.p.r., i.r. and magnetic-susceptibility studies.", "contents": "Low-temperature kinetics of the reactions of fully reduced membrane-bound cytochrome oxidase with oxygen in the Soret, alpha and near-infrared regions. The kinetics of the reaction of fully reduced membrane-bound cytochrome oxidase with O2 obtained in the Soret, alpha and near-i.r. regions were analysed, and the contributions of the three intermediates of the reaction [Clore & Chance (1978) Biochem. J. 173, 799--810] to seven wavelength pairs (430--463, 444--463, 590--630, 608--630, 740--940, 790--940 and 830--940 nm) were determined. The nature of the intermediates is discussed on the basis of the data in the present paper together with data in the literature from optical wavelength scanning, e.p.r., i.r. and magnetic-susceptibility studies."}
{"id": "PMID:219848", "title": "Purification and characterization of the ferredoxin component of 25-hydroxycholecalciferol 1 alpha-hydroxylase.", "content": "The chick kidney mitochondrial iron--sulphur protein (ferredoxin), a component of the NADPH--cytochrome P-450 reductase functional in the 1 alpha-hydroxylation of 25-hydroxycholecalciferol, was purified to homogeneity by chromatography on DEAE-cellulose, gel filtration on Sephadex G-100 and preparative electrophoresis on polyacrylamide gel. A novel NADPH--cytochrome c reductase assay utilizing crude renal NADPH--ferredoxin reductase was used for the detection of the ferredoxin. A mol. wt. of 53 000 was determined by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis and by Sephadex G-100 gel filtration of the 125I-labelled ferredoxin. The ferredoxin has a sedimentation constant (S 20, w) of 2.66S, an A411/A280 of 0.4, and a molar absorptivity of 7300 cm-1 . M-1. The electron-paramagnetic-resonance spectrum after reduction with Methyl Viologen and dithionite was characteristic of ferredoxins with signals at g = 1.956 and 2.025. Two iron and two labile sulphur atoms per molecule of ferredoxin were released by acid. Ouchterlony immunodiffusion tests by using goat anti-(bovine adrenal ferredoxin) antiserum showed precipitin reactions with the bovine adrenal ferredoxin and the chick renal ferredoxin as antigens, suggesting that the renal ferredoxin shares antigenic determinants(s) with the natural adrenal antigen. Amino acid analysis showed that of the total number of residues per molecule of ferredoxin, glutamic acid and aspartic acid are the most abundant residues, comprising 17 and 15% respectively.", "contents": "Purification and characterization of the ferredoxin component of 25-hydroxycholecalciferol 1 alpha-hydroxylase. The chick kidney mitochondrial iron--sulphur protein (ferredoxin), a component of the NADPH--cytochrome P-450 reductase functional in the 1 alpha-hydroxylation of 25-hydroxycholecalciferol, was purified to homogeneity by chromatography on DEAE-cellulose, gel filtration on Sephadex G-100 and preparative electrophoresis on polyacrylamide gel. A novel NADPH--cytochrome c reductase assay utilizing crude renal NADPH--ferredoxin reductase was used for the detection of the ferredoxin. A mol. wt. of 53 000 was determined by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis and by Sephadex G-100 gel filtration of the 125I-labelled ferredoxin. The ferredoxin has a sedimentation constant (S 20, w) of 2.66S, an A411/A280 of 0.4, and a molar absorptivity of 7300 cm-1 . M-1. The electron-paramagnetic-resonance spectrum after reduction with Methyl Viologen and dithionite was characteristic of ferredoxins with signals at g = 1.956 and 2.025. Two iron and two labile sulphur atoms per molecule of ferredoxin were released by acid. Ouchterlony immunodiffusion tests by using goat anti-(bovine adrenal ferredoxin) antiserum showed precipitin reactions with the bovine adrenal ferredoxin and the chick renal ferredoxin as antigens, suggesting that the renal ferredoxin shares antigenic determinants(s) with the natural adrenal antigen. Amino acid analysis showed that of the total number of residues per molecule of ferredoxin, glutamic acid and aspartic acid are the most abundant residues, comprising 17 and 15% respectively."}
{"id": "PMID:219849", "title": "Prolyl 3-hydroxylase and 4-hydroxylase activities in certain rat and chick-embryo tissues and age-related changes in their activities in the rat.", "content": "Prolyl 3-hydroxylase activity, expressed per unit of extract protein, was much higher in rat kidney cortex than in the lung, liver or skin. A marked decrease in activity was found in the kidney cortex, liver and skin beyond 10 days of age. The ratio of prolyl 3-hydroxylase to 4-hydroxylase activity in the kidney cortex was 13--17 times that in the skin, that in the liver 6--8 times, and that in the lung about twice the value for the skin, there being no changes in this ratio with age. In 16-day chick embryos the highest ratios of prolyl 3-hydroxylase to 4-hydroxylase activity were found in the liver, heart, lens, aorta and kidney, and the lowest ratios in tendon, cartilage, cartilaginous and membranous bone and skin. The results suggest that the differences in the extent of prolyl 3-hydroxylation between various collagens can in part be explained by differences in the amount of prolyl e-hydroxylase activity among different cells.", "contents": "Prolyl 3-hydroxylase and 4-hydroxylase activities in certain rat and chick-embryo tissues and age-related changes in their activities in the rat. Prolyl 3-hydroxylase activity, expressed per unit of extract protein, was much higher in rat kidney cortex than in the lung, liver or skin. A marked decrease in activity was found in the kidney cortex, liver and skin beyond 10 days of age. The ratio of prolyl 3-hydroxylase to 4-hydroxylase activity in the kidney cortex was 13--17 times that in the skin, that in the liver 6--8 times, and that in the lung about twice the value for the skin, there being no changes in this ratio with age. In 16-day chick embryos the highest ratios of prolyl 3-hydroxylase to 4-hydroxylase activity were found in the liver, heart, lens, aorta and kidney, and the lowest ratios in tendon, cartilage, cartilaginous and membranous bone and skin. The results suggest that the differences in the extent of prolyl 3-hydroxylation between various collagens can in part be explained by differences in the amount of prolyl e-hydroxylase activity among different cells."}
{"id": "PMID:219850", "title": "Effects of food deprivation on ketonaemia, ketogenesis and hepatic intermediary metabolism in the non-lactating dairy cow.", "content": "1. The aim of this work was to investigate why non-lactating dairy cows are less susceptible to the development of ketonaemia during food deprivation than are dairy cows in early lactation. 2. The first experiment (Expt. A) consisted of determining the effect of 6 days of food deprivation on the concentrations of ketone bodies, and of metabolites related to the regulation of ketogenesis, in jugular blood and liver of non-lactating cows. 3. During the food deprivation, blood ketone-body concentrations rose significantly, but to a value that was only 16% of that achieved in lactating cows deprived of food for 6 days [Baird, Heitzman & Hibbitt (1972) Biochem. J. 128, 1311--1318]. 4. In the liver, food deprivation caused: a rise in ketone-body concentrations; a fall in the concentration of glycogen and of various intermediates of the Embden-Meyerhof pathway and the tricarboxylic acid cycle; an increase in cytoplasmic reduction; a decrease in the [total NAD+]/[total NADH] ratio; a decrease in energy charge. These changes were all qualitatively similar to those previously observed in the livers of the food-deprived lactating cows. 5. There appeared therefore to be a discrepancy in the food-deprived non-lactating cows between the absence of marked ketonaemia and the occurrence of metabolic changes within the liver suggesting increased hepatic ketogenesis. This discrepancy was partially resolved in Expt. B by the observation in two catheterized non-lactating cows that, although there was a 2-fold increase in hepatic ketogenesis during 6 days of food deprivation, ketogenesis from the splanchnic bed as a whole (i.e. gut and liver combined) declined slightly owing to cessation of gut ketogenesis.", "contents": "Effects of food deprivation on ketonaemia, ketogenesis and hepatic intermediary metabolism in the non-lactating dairy cow. 1. The aim of this work was to investigate why non-lactating dairy cows are less susceptible to the development of ketonaemia during food deprivation than are dairy cows in early lactation. 2. The first experiment (Expt. A) consisted of determining the effect of 6 days of food deprivation on the concentrations of ketone bodies, and of metabolites related to the regulation of ketogenesis, in jugular blood and liver of non-lactating cows. 3. During the food deprivation, blood ketone-body concentrations rose significantly, but to a value that was only 16% of that achieved in lactating cows deprived of food for 6 days [Baird, Heitzman & Hibbitt (1972) Biochem. J. 128, 1311--1318]. 4. In the liver, food deprivation caused: a rise in ketone-body concentrations; a fall in the concentration of glycogen and of various intermediates of the Embden-Meyerhof pathway and the tricarboxylic acid cycle; an increase in cytoplasmic reduction; a decrease in the [total NAD+]/[total NADH] ratio; a decrease in energy charge. These changes were all qualitatively similar to those previously observed in the livers of the food-deprived lactating cows. 5. There appeared therefore to be a discrepancy in the food-deprived non-lactating cows between the absence of marked ketonaemia and the occurrence of metabolic changes within the liver suggesting increased hepatic ketogenesis. This discrepancy was partially resolved in Expt. B by the observation in two catheterized non-lactating cows that, although there was a 2-fold increase in hepatic ketogenesis during 6 days of food deprivation, ketogenesis from the splanchnic bed as a whole (i.e. gut and liver combined) declined slightly owing to cessation of gut ketogenesis."}
{"id": "PMID:219851", "title": "Relationship between hormonal activation of phosphatidylinositol hydrolysis, fluid secretion and calcium flux in the blowfly salivary gland.", "content": "The addition of 5-hydroxytryptamine to the isolated blowfly salivary gland stimulates fluid secretion, transepithelial calcium transport and the breakdown of 32P- or 3H-labelled phosphatidylinositol The breakdown of [32P]phosphatidylcholine and [32P]-phosphatidylethanolamine was not stimulated by 5-hydroxytryptamine. In salivary glands incubated with myo-[2-3H]inositol for 1--3 h, more than 95% of the label retained by the tissue was in the form of phosphatidylinositol. The addition of 5-hydroxytryptamine resulted in an increase in the accumulation of label in intracellular inositol 1:2-cyclic phosphate, inositol 1-phosphate and free inositol along with an increase in the release of [3H]inositol to the medium and saliva. The release of [3H]inositol to the medium served as a sensitive indicator of phosphatidylinositol breakdown. The release of [3H]inositol was not increased by cyclic AMP or the bivalent-cation ionophore A23187 under conditions in which salivary secretion was accelerated. The stimulation of fluid secretion by low concentrations of 5-hydroxytryptamine was potentiated by 3-isobutyl-1-methylxanthine, which had no effect on inositol release. The stimulation of fluid secretion by 5-hydroxytryptamine was greatly reduced in calcium-free buffer, but the breakdown of phosphatidylinositol continued at the same rate in the absence of calcium. These results support the hypothesis that breakdown of phosphatidylinositol by 5-hydroxytryptamine is involved in the gating of calcium.", "contents": "Relationship between hormonal activation of phosphatidylinositol hydrolysis, fluid secretion and calcium flux in the blowfly salivary gland. The addition of 5-hydroxytryptamine to the isolated blowfly salivary gland stimulates fluid secretion, transepithelial calcium transport and the breakdown of 32P- or 3H-labelled phosphatidylinositol The breakdown of [32P]phosphatidylcholine and [32P]-phosphatidylethanolamine was not stimulated by 5-hydroxytryptamine. In salivary glands incubated with myo-[2-3H]inositol for 1--3 h, more than 95% of the label retained by the tissue was in the form of phosphatidylinositol. The addition of 5-hydroxytryptamine resulted in an increase in the accumulation of label in intracellular inositol 1:2-cyclic phosphate, inositol 1-phosphate and free inositol along with an increase in the release of [3H]inositol to the medium and saliva. The release of [3H]inositol to the medium served as a sensitive indicator of phosphatidylinositol breakdown. The release of [3H]inositol was not increased by cyclic AMP or the bivalent-cation ionophore A23187 under conditions in which salivary secretion was accelerated. The stimulation of fluid secretion by low concentrations of 5-hydroxytryptamine was potentiated by 3-isobutyl-1-methylxanthine, which had no effect on inositol release. The stimulation of fluid secretion by 5-hydroxytryptamine was greatly reduced in calcium-free buffer, but the breakdown of phosphatidylinositol continued at the same rate in the absence of calcium. These results support the hypothesis that breakdown of phosphatidylinositol by 5-hydroxytryptamine is involved in the gating of calcium."}
{"id": "PMID:219866", "title": "How does insulin stimulate glycogen synthesis?", "content": "One of the important effects of insulin on intracellular metabolism is its ability to stimulate the synthesis of glycogen in muscle and liver. It does this by promoting a net decrease in the extent of phosphorylation of glycogen synthase, the rate-limiting enzyme in the pathway of glycogen synthesis, which increases its activity. Several years ago glycogen synthase was shown to be phosphorylated and inactivated by cyclic AMP-dependent protein kinase in vitro, suggesting that the effect of insulin on glycogen synthesis, and perhaps other intracellular processes, might be explainable in terms of the ability of the hormone to decrease the concentration of tissue cyclic AMP. However, the subsequent failure to detect a decrease in cyclic AMP concentration in muscle under conditions where glycogen synthase activity was stimulated by insulin, coupled with the discovery of a second glycogen synthase kinase whose activity is unaffected by cyclic nucleotides, now suggests the possibility that insulin may regulate the activity of a different class of protein kinase, through its own \"second messenger\". The identification and characterization of glycogen synthase kinase-2 and recent information about the regulation of glycogen synthase by phosphorylation-dephosphorylation in vitro and in vivo are presented.", "contents": "How does insulin stimulate glycogen synthesis? One of the important effects of insulin on intracellular metabolism is its ability to stimulate the synthesis of glycogen in muscle and liver. It does this by promoting a net decrease in the extent of phosphorylation of glycogen synthase, the rate-limiting enzyme in the pathway of glycogen synthesis, which increases its activity. Several years ago glycogen synthase was shown to be phosphorylated and inactivated by cyclic AMP-dependent protein kinase in vitro, suggesting that the effect of insulin on glycogen synthesis, and perhaps other intracellular processes, might be explainable in terms of the ability of the hormone to decrease the concentration of tissue cyclic AMP. However, the subsequent failure to detect a decrease in cyclic AMP concentration in muscle under conditions where glycogen synthase activity was stimulated by insulin, coupled with the discovery of a second glycogen synthase kinase whose activity is unaffected by cyclic nucleotides, now suggests the possibility that insulin may regulate the activity of a different class of protein kinase, through its own \"second messenger\". The identification and characterization of glycogen synthase kinase-2 and recent information about the regulation of glycogen synthase by phosphorylation-dephosphorylation in vitro and in vivo are presented."}
{"id": "PMID:219867", "title": "Hormonal control of adipose-tissue lipolysis.", "content": "Adipose-tissue triacylglycerol is the major energy store in man. The physiological importance and biochemical mechanism of the hormonal control of lipolysis in white adipose tissue is reviewed. Rates of lipolysis and fatty acid release observed when adipose tissue is incubated in vitro are compared with rates of triacylglycerol turnover in man. It appears that enhanced rates of lipolysis in vivo, for example during fasting and exercise, may be a substantial fraction of the maximum obtainable by hormone stimulation in vitro. There is considerable species variation in the hormonal sensitivity of adipose tissue. Some hormones that stimulate lipolysis in vitro may not be significant lipolytic agents at physiological concentrations in vivo. In man and rat, the most important acutely acting lipolytic and anti-lipolytic hormones are catecholamines and insulin respectively. The sympathetic nervous system may play a role at least as important as circulating catecholamines in the mobilization of stored triacylglycerol. The effects of acute lipolytic hormones are modulated in the long term by corticosteroids and thyroid hormone. Stimulation of lipolysis is believed to be mediated by the increased intracellular cyclic AMP concentration that occurs after interaction of hormones with specific receptors in the plasma membrane. The properties of membrane receptors, adenylate cyclase, cyclic AMP phosphodiesterase, cyclic AMP-dependent protein kinase and triacylglycerol lipase, as studied in rat and human adipose tissue, are discussed. Several features of the action of lipolytic hormones in vitro are difficult to account for by the hypothesis that cyclic AMP is the only \"second messenger\" regulating lipase activity. These include anomalous effects of hormones at high concentrations and the possible existence of feedback inhibition limiting the accumulation of cyclic AMP and the stimulation of lipolysis. The mechanism of the anti-lipolytic action of insulin is at present unknown.", "contents": "Hormonal control of adipose-tissue lipolysis. Adipose-tissue triacylglycerol is the major energy store in man. The physiological importance and biochemical mechanism of the hormonal control of lipolysis in white adipose tissue is reviewed. Rates of lipolysis and fatty acid release observed when adipose tissue is incubated in vitro are compared with rates of triacylglycerol turnover in man. It appears that enhanced rates of lipolysis in vivo, for example during fasting and exercise, may be a substantial fraction of the maximum obtainable by hormone stimulation in vitro. There is considerable species variation in the hormonal sensitivity of adipose tissue. Some hormones that stimulate lipolysis in vitro may not be significant lipolytic agents at physiological concentrations in vivo. In man and rat, the most important acutely acting lipolytic and anti-lipolytic hormones are catecholamines and insulin respectively. The sympathetic nervous system may play a role at least as important as circulating catecholamines in the mobilization of stored triacylglycerol. The effects of acute lipolytic hormones are modulated in the long term by corticosteroids and thyroid hormone. Stimulation of lipolysis is believed to be mediated by the increased intracellular cyclic AMP concentration that occurs after interaction of hormones with specific receptors in the plasma membrane. The properties of membrane receptors, adenylate cyclase, cyclic AMP phosphodiesterase, cyclic AMP-dependent protein kinase and triacylglycerol lipase, as studied in rat and human adipose tissue, are discussed. Several features of the action of lipolytic hormones in vitro are difficult to account for by the hypothesis that cyclic AMP is the only \"second messenger\" regulating lipase activity. These include anomalous effects of hormones at high concentrations and the possible existence of feedback inhibition limiting the accumulation of cyclic AMP and the stimulation of lipolysis. The mechanism of the anti-lipolytic action of insulin is at present unknown."}
{"id": "PMID:219868", "title": "Effect of proxyphylline and benzopyrones on the cerebrocortical NAD/NADH redox state and reflectance in haemorrhagic shock.", "content": "The effect of 7-(2-hydroxypropyl)theophylline (proxyphylline) and coumarin (Theokal) on cerebrocortical NAD/NADH redox state and vascular volume was investigated in cats in haemorrhagic shock. The influence of these drugs on cortical NADH and UV reflectance responses induced by nitrogen breathing and electrical stimulation of the cortex was also studied. The results are summarized as follows: 1. Proxyphylline administration does not change the cortical vascular volume but shifts the NAD/NADH redox state towards oxidation. This occurs in spite of the significant arterial blood pressure drop. 2. Coumarin dilates the cerebrocortical vessels and increases the cerebral blood flow. Since NAD reduction was obtained though CBF increased, it is presumed that coumarin increased the rate of glycolysis and the lactate/pyruvate ratio. 3. Proxyphylline increased, coumarin decreased the amplitude of the anoxic NAD reduction. The stimulation induced NAD and reflectance reactions were not effected by coumarin. 4. Finally it is concluded that the beneficial effect of Theokal on brain circulation and metabolism in haemorrhagic shock is related with different mechanisms to both substances, proxyphylline and 5,6-benzo-alpha-pyrone.", "contents": "Effect of proxyphylline and benzopyrones on the cerebrocortical NAD/NADH redox state and reflectance in haemorrhagic shock. The effect of 7-(2-hydroxypropyl)theophylline (proxyphylline) and coumarin (Theokal) on cerebrocortical NAD/NADH redox state and vascular volume was investigated in cats in haemorrhagic shock. The influence of these drugs on cortical NADH and UV reflectance responses induced by nitrogen breathing and electrical stimulation of the cortex was also studied. The results are summarized as follows: 1. Proxyphylline administration does not change the cortical vascular volume but shifts the NAD/NADH redox state towards oxidation. This occurs in spite of the significant arterial blood pressure drop. 2. Coumarin dilates the cerebrocortical vessels and increases the cerebral blood flow. Since NAD reduction was obtained though CBF increased, it is presumed that coumarin increased the rate of glycolysis and the lactate/pyruvate ratio. 3. Proxyphylline increased, coumarin decreased the amplitude of the anoxic NAD reduction. The stimulation induced NAD and reflectance reactions were not effected by coumarin. 4. Finally it is concluded that the beneficial effect of Theokal on brain circulation and metabolism in haemorrhagic shock is related with different mechanisms to both substances, proxyphylline and 5,6-benzo-alpha-pyrone."}
{"id": "PMID:219869", "title": "[Biochemical and clinical studies on the influence of 2-mercaptopropionylglycine on liver cell function (author's transl)].", "content": "2-Mercaptopropionylglycine was used for the treatment of chronic hepatitis. The drugs showed very good clinical results. In biochemical studies it was found that there was no effect on phosphate transport. Instead, there was an increase of reactive SH-groups sensitive to oligomycin in the membrane of rat liver mitochondria. The ATPase activity in mitochondria was diminished, while ATP-contents of the mitochondrial suspensions were increased by the drug. In the presence of ATP-MG++ there was an increase of oligomycin-sensitive contraction of the mitochondria. In aged mitochondria, the P/O ratios were improved. Reversal of electron transport with formation of NADH by succinate in the presence of rotenone and ATP was, concentration dependently, improved by MPG. Thus, MGP obviously acts at some specific sulfhydryl groups of the mitochondrion. It is concluded that the action of the drug in chronic hepatitis may be interpreted via an improvement of mitochondrial function.", "contents": "[Biochemical and clinical studies on the influence of 2-mercaptopropionylglycine on liver cell function (author's transl)]. 2-Mercaptopropionylglycine was used for the treatment of chronic hepatitis. The drugs showed very good clinical results. In biochemical studies it was found that there was no effect on phosphate transport. Instead, there was an increase of reactive SH-groups sensitive to oligomycin in the membrane of rat liver mitochondria. The ATPase activity in mitochondria was diminished, while ATP-contents of the mitochondrial suspensions were increased by the drug. In the presence of ATP-MG++ there was an increase of oligomycin-sensitive contraction of the mitochondria. In aged mitochondria, the P/O ratios were improved. Reversal of electron transport with formation of NADH by succinate in the presence of rotenone and ATP was, concentration dependently, improved by MPG. Thus, MGP obviously acts at some specific sulfhydryl groups of the mitochondrion. It is concluded that the action of the drug in chronic hepatitis may be interpreted via an improvement of mitochondrial function."}
{"id": "PMID:219871", "title": "[Effect of metoclopramide on growth hormone (GH) release induced with ACTH].", "content": "We examined 10 volunteers subjects, sound and exempt from endocrine disease. The rapid injection of 0,25 mg of ACTH (Synacten) was followed by a distinct increase of plasma Growth Hormone (GH) within 30 or 60 min in 9 of 10 normal volunteers. The test were then repeated in the 12 \"responders\" after previous subministration of Metoclopramide and the GH response was totally abolished.", "contents": "[Effect of metoclopramide on growth hormone (GH) release induced with ACTH]. We examined 10 volunteers subjects, sound and exempt from endocrine disease. The rapid injection of 0,25 mg of ACTH (Synacten) was followed by a distinct increase of plasma Growth Hormone (GH) within 30 or 60 min in 9 of 10 normal volunteers. The test were then repeated in the 12 \"responders\" after previous subministration of Metoclopramide and the GH response was totally abolished."}
{"id": "PMID:219872", "title": "[Effect of TRH on growth hormone (GH) release induced with ACTH].", "content": "We examined 14 volunteers subjects sound and exempt from en docrine disease. The rapid injection of 0,25 mg of ACTH (Synacten) was followed by a distinct increase of plasma Hormone (GH) within 30 or 60 min in 12 of 14 normal volunteers. The test were the 12 \"responders after previous subministration of 200 g of TRH and the GH response was totally abolished.", "contents": "[Effect of TRH on growth hormone (GH) release induced with ACTH]. We examined 14 volunteers subjects sound and exempt from en docrine disease. The rapid injection of 0,25 mg of ACTH (Synacten) was followed by a distinct increase of plasma Hormone (GH) within 30 or 60 min in 12 of 14 normal volunteers. The test were the 12 \"responders after previous subministration of 200 g of TRH and the GH response was totally abolished."}
{"id": "PMID:219877", "title": "Further studies on antitumour responses induced by short-term pretreatment with syngeneic tumour cells.", "content": "The ability of s.c. injected tumour cells to specifically inhibit the growth of similar cells injected i.v. 2 days later has been confirmed. The capacity of tumour cells to elicit this effect varies form tumour to tumour. Furthermore, it is more readily achieved with cultured than with freshly excised tumour cells. The superior effect elicited by cultured tumour cells was not overcome by treating them with trypsin or pronase. The protection achieved was impaired in T-cell-depleted mice and mice which had been irradiated (400 rad) prior to pretreatment. In contrast, it was not affected by administration of silica, sodium aurothiomolate or cortisone acetate. The results imply that T-cell-dependent responses are involved in the protection conferred by pre-injecting tumour cells shortly before i.v. challenge.", "contents": "Further studies on antitumour responses induced by short-term pretreatment with syngeneic tumour cells. The ability of s.c. injected tumour cells to specifically inhibit the growth of similar cells injected i.v. 2 days later has been confirmed. The capacity of tumour cells to elicit this effect varies form tumour to tumour. Furthermore, it is more readily achieved with cultured than with freshly excised tumour cells. The superior effect elicited by cultured tumour cells was not overcome by treating them with trypsin or pronase. The protection achieved was impaired in T-cell-depleted mice and mice which had been irradiated (400 rad) prior to pretreatment. In contrast, it was not affected by administration of silica, sodium aurothiomolate or cortisone acetate. The results imply that T-cell-dependent responses are involved in the protection conferred by pre-injecting tumour cells shortly before i.v. challenge."}
{"id": "PMID:219878", "title": "Ablation of murine jejunal crypts by alkylating agents.", "content": "The gut microcolony assay has been used to measure damage to intestinal crypts by single and split doses of 3 alkylating agents: mechlorethamine hydrochloride (HN2), bis-chloroethyl-nitrosourea (BCNU) and isopropyl methane sulphonate (IMS). The single-dose survival curves for whole crypts were distinguished by extrapolation numbers (3.0, 176 and 1.5 respectively) that were lower than most previously published values for assay by irradiation. Significant sparing of crypts occurred when doses of HN2 or BCNU, but not IMS, were given in 2 equal fractions separated by more than 2 h. Deduced D0 values for those cells from which crypts regenerate were 1.9 mg/kg HN2, 19 mg/kg BCNU and 487 mg/kg IMS.", "contents": "Ablation of murine jejunal crypts by alkylating agents. The gut microcolony assay has been used to measure damage to intestinal crypts by single and split doses of 3 alkylating agents: mechlorethamine hydrochloride (HN2), bis-chloroethyl-nitrosourea (BCNU) and isopropyl methane sulphonate (IMS). The single-dose survival curves for whole crypts were distinguished by extrapolation numbers (3.0, 176 and 1.5 respectively) that were lower than most previously published values for assay by irradiation. Significant sparing of crypts occurred when doses of HN2 or BCNU, but not IMS, were given in 2 equal fractions separated by more than 2 h. Deduced D0 values for those cells from which crypts regenerate were 1.9 mg/kg HN2, 19 mg/kg BCNU and 487 mg/kg IMS."}
{"id": "PMID:219885", "title": "Synthesis of herpes simplex virus DNA in isolated chromatin.", "content": "Herpes simplex virus DNA synthesis was studied in isolated chromatin (HSV chromatin) of African green monkey kidney (RC-37) cells after HSV type 1 infection. After optimizing the in vitro system, HSV chromatin was shown to synthesize both viral and cellular DNA at ratios identical with those seen in vivo. After 30 min of DNA synthesis in vitro, the DNA products were identical in size to the prelabeled parental DNA. More than 60% of the newly synthesized single-stranded DNA fragments sedimented with a sedimentation constant of greater than 10 S. HSV DNA polymerase was found to be responsible for the synthesis of 80% of all in vitro made viral and most likely also cellular DNA sequences.", "contents": "Synthesis of herpes simplex virus DNA in isolated chromatin. Herpes simplex virus DNA synthesis was studied in isolated chromatin (HSV chromatin) of African green monkey kidney (RC-37) cells after HSV type 1 infection. After optimizing the in vitro system, HSV chromatin was shown to synthesize both viral and cellular DNA at ratios identical with those seen in vivo. After 30 min of DNA synthesis in vitro, the DNA products were identical in size to the prelabeled parental DNA. More than 60% of the newly synthesized single-stranded DNA fragments sedimented with a sedimentation constant of greater than 10 S. HSV DNA polymerase was found to be responsible for the synthesis of 80% of all in vitro made viral and most likely also cellular DNA sequences."}
{"id": "PMID:219887", "title": "Photoreductive titration of the resonance Raman spectra of cytochrome oxidase in whole mitochondria.", "content": "A photoreductive titration of the resonance Raman (RR) spectra of cytochrome c oxidase in whole mitochondria was recorded by exploiting the preferential enhancement of the Raman signals of reduced cytochrome oxidase excited at 441.6 nm. When the sample was cooled to about--10 degrees C, it was possible to slow down the photoreductive effect of the laser and to record RR spectra at various states of reduction. Compared to the earliest recorded scan (most oxidized), the dithionite-reduced sample shows the appearance of new bands at 216, 363, 560, and 1665 cm-1. At intermediate stages of photoreduction, the 216- and 560-cm-1 bands appear before the 363- and 1665-cm-1 bands; photoreduction induces full intensity in the former bands, whereas the latter bands are photoreduced to 50% of the dithionite-reduced intensity. The relative intensities of a doublet at 1609--1623 cm-1 are affected by reduction: the band at 1609 cm-1 is weaker in the earlier scans; in later scans this band has grown to equal intensity with the 1623-cm-1 band. We conclude that this reductive titration of the RR spectrum of cytochrome c oxidase reflects three states in its reduction. The behavior of the doublet at 1609--1623 cm-1 suggests that the two hemes are nonequivalent but interacting. The band at 216 cm-1 may be indicative of an iron-copper interaction that is affected by the presence of external ligands.", "contents": "Photoreductive titration of the resonance Raman spectra of cytochrome oxidase in whole mitochondria. A photoreductive titration of the resonance Raman (RR) spectra of cytochrome c oxidase in whole mitochondria was recorded by exploiting the preferential enhancement of the Raman signals of reduced cytochrome oxidase excited at 441.6 nm. When the sample was cooled to about--10 degrees C, it was possible to slow down the photoreductive effect of the laser and to record RR spectra at various states of reduction. Compared to the earliest recorded scan (most oxidized), the dithionite-reduced sample shows the appearance of new bands at 216, 363, 560, and 1665 cm-1. At intermediate stages of photoreduction, the 216- and 560-cm-1 bands appear before the 363- and 1665-cm-1 bands; photoreduction induces full intensity in the former bands, whereas the latter bands are photoreduced to 50% of the dithionite-reduced intensity. The relative intensities of a doublet at 1609--1623 cm-1 are affected by reduction: the band at 1609 cm-1 is weaker in the earlier scans; in later scans this band has grown to equal intensity with the 1623-cm-1 band. We conclude that this reductive titration of the RR spectrum of cytochrome c oxidase reflects three states in its reduction. The behavior of the doublet at 1609--1623 cm-1 suggests that the two hemes are nonequivalent but interacting. The band at 216 cm-1 may be indicative of an iron-copper interaction that is affected by the presence of external ligands."}
{"id": "PMID:219889", "title": "Quenching of intrinsic tryptophan fluorescence in membranes of rat pituitary cells.", "content": "The GH4C1 strain of hormone-producing rat pituitary cells has specific receptors for the tripeptide thyrotropin-releasing hormone (TRH). Membranes prepared from GH4C1 cells show intrinsic tryptophan fluorescence which was quenched by low concentrations (10--100 nM) of TRH and Ntau-methyl TRH but not by biologically inactive analogs of TRH. Membranes from GH4C1 cells were subjected to thermal denaturation. A conformational transition was noted above 40 degrees C and an irreversible denaturation was observed at 52 degrees C. TRH-induced quenching of intrinsic fluorescence was lost completely in membranes previously incubated for 10 min at 30 degrees C while loss of [3H]-TRH binding was only about 20% at this temperature. Collisional quenching by iodide revealed that about 38% of the tryptophanyl residues in GH4C1 membranes were exposed to solvent. Quenching by TRH occurred with a shift in wavelength maximum from 336 to 342 nm suggesting that few of the tryptophanyl residues quenched by the tripeptide are totally exposed. Membranes prepared from cells preincubated with 20 nM TRH for 48 h, in which TRH receptors were decreased to 30% of control values, showed no quenching of tryptophan fluorescence in response to freshly added TRH. We conclude that the TRH-receptor interaction in GH4C1 cells is associated with a change in membrane conformation that can be measured by differential spectrofluorometry of intrinsic tryptophan fluorescence.", "contents": "Quenching of intrinsic tryptophan fluorescence in membranes of rat pituitary cells. The GH4C1 strain of hormone-producing rat pituitary cells has specific receptors for the tripeptide thyrotropin-releasing hormone (TRH). Membranes prepared from GH4C1 cells show intrinsic tryptophan fluorescence which was quenched by low concentrations (10--100 nM) of TRH and Ntau-methyl TRH but not by biologically inactive analogs of TRH. Membranes from GH4C1 cells were subjected to thermal denaturation. A conformational transition was noted above 40 degrees C and an irreversible denaturation was observed at 52 degrees C. TRH-induced quenching of intrinsic fluorescence was lost completely in membranes previously incubated for 10 min at 30 degrees C while loss of [3H]-TRH binding was only about 20% at this temperature. Collisional quenching by iodide revealed that about 38% of the tryptophanyl residues in GH4C1 membranes were exposed to solvent. Quenching by TRH occurred with a shift in wavelength maximum from 336 to 342 nm suggesting that few of the tryptophanyl residues quenched by the tripeptide are totally exposed. Membranes prepared from cells preincubated with 20 nM TRH for 48 h, in which TRH receptors were decreased to 30% of control values, showed no quenching of tryptophan fluorescence in response to freshly added TRH. We conclude that the TRH-receptor interaction in GH4C1 cells is associated with a change in membrane conformation that can be measured by differential spectrofluorometry of intrinsic tryptophan fluorescence."}
{"id": "PMID:219890", "title": "Exchangeability and rate of flip-flop of phosphatidylcholine in large unilamellar vesicles, cholate dialysis vesicles, and cytochrome oxidase vesicles.", "content": "Three model membrane systems have been characterized in terms of their interaction with phospholipid exchange proteins. Large unilamellar vesicles of phosphatidylcholine prepared by ether vaporization are shown to be homogeneous by gel filtration. Phospholipid exchange proteins from three sources are capable of catalyzing the rapid exchange of approximately half of the phospholipid from these vesicles. The remaining pool of radioactive phospholipid is virtually nonexchangeable (t1/2 of several days). Small unilamellar vesicles of phosphatidylcholine prepared by cholate dialysis also exhibit two pools of phospholipid (65% rapidly exchangable, 35% very slowly exchangeable) when incubated with beef liver phospholipid exchange protein. Cytochrome oxidase vesicles prepared both by a cholate dialysis method and by a direct incorporation method have been fractionated on a Ficoll discontinuous gradient, and tested for interaction with beef heart exchange protein. Two pools of phospholipid are once again observed (70% rapidly exchangable, 30% nonexchangeable), even for vesicles which have incorporated the transmembranous enzyme at a phospholipid to protein weight ratio of 2. The size of the rapidly exchangeable pool of phosphatidylcholine for each of the vesicle systems is consistent with the calculated fraction of phospholipid in the outer monolayer. The extremely slow rate of exchange of the second pool of the second pool of phospholipid reflects the virtual nonexistence of phospholipid flip-flop in any of these model membranes.", "contents": "Exchangeability and rate of flip-flop of phosphatidylcholine in large unilamellar vesicles, cholate dialysis vesicles, and cytochrome oxidase vesicles. Three model membrane systems have been characterized in terms of their interaction with phospholipid exchange proteins. Large unilamellar vesicles of phosphatidylcholine prepared by ether vaporization are shown to be homogeneous by gel filtration. Phospholipid exchange proteins from three sources are capable of catalyzing the rapid exchange of approximately half of the phospholipid from these vesicles. The remaining pool of radioactive phospholipid is virtually nonexchangeable (t1/2 of several days). Small unilamellar vesicles of phosphatidylcholine prepared by cholate dialysis also exhibit two pools of phospholipid (65% rapidly exchangable, 35% very slowly exchangeable) when incubated with beef liver phospholipid exchange protein. Cytochrome oxidase vesicles prepared both by a cholate dialysis method and by a direct incorporation method have been fractionated on a Ficoll discontinuous gradient, and tested for interaction with beef heart exchange protein. Two pools of phospholipid are once again observed (70% rapidly exchangable, 30% nonexchangeable), even for vesicles which have incorporated the transmembranous enzyme at a phospholipid to protein weight ratio of 2. The size of the rapidly exchangeable pool of phosphatidylcholine for each of the vesicle systems is consistent with the calculated fraction of phospholipid in the outer monolayer. The extremely slow rate of exchange of the second pool of the second pool of phospholipid reflects the virtual nonexistence of phospholipid flip-flop in any of these model membranes."}
{"id": "PMID:219891", "title": "Divalent cation binding to phospholipid veiscles. Dependence on temperature and lipid fluidity.", "content": "Mn2+ binding to vesicles prepared from several different species of anionic phospholipids was determined as a function of temperature by electron paramagnetic resonance (EPR). The Mn2+ affinities of phosphatidylserine, cardiolipin and egg yolk phosphatidylglycerol all increased monitonically with temperature. Vesicles prepared from hydrogenated and natural (bovine) phosphatidylserine were monitored with respect to hydrocarbon chain fluidity as well as Mn2+ binding. Contrary to expectations based on surface potential considerations, the affinity of phosphatidylserine for divalent cations was apparently not lowered in going from the gel state to the lipid crystalline state of the bilayer. The results are instead consistent with an enhancement in cation affinity with increased lipid fluidity. Dipalmitoyl phosphatidylglycerol vesicle fluidity and Mn2+ binding were also studied with EPR. A large reduction in the measured Mn2+ affinity accompained melting of the phospholipid, but observed hysteresis in the temperature dependence of the binding render uncertain any simple explanation based on changes in surface potential. Supplementary light scattering data indicated that vesicle aggregation was involved in the hysteresis phenomena.", "contents": "Divalent cation binding to phospholipid veiscles. Dependence on temperature and lipid fluidity. Mn2+ binding to vesicles prepared from several different species of anionic phospholipids was determined as a function of temperature by electron paramagnetic resonance (EPR). The Mn2+ affinities of phosphatidylserine, cardiolipin and egg yolk phosphatidylglycerol all increased monitonically with temperature. Vesicles prepared from hydrogenated and natural (bovine) phosphatidylserine were monitored with respect to hydrocarbon chain fluidity as well as Mn2+ binding. Contrary to expectations based on surface potential considerations, the affinity of phosphatidylserine for divalent cations was apparently not lowered in going from the gel state to the lipid crystalline state of the bilayer. The results are instead consistent with an enhancement in cation affinity with increased lipid fluidity. Dipalmitoyl phosphatidylglycerol vesicle fluidity and Mn2+ binding were also studied with EPR. A large reduction in the measured Mn2+ affinity accompained melting of the phospholipid, but observed hysteresis in the temperature dependence of the binding render uncertain any simple explanation based on changes in surface potential. Supplementary light scattering data indicated that vesicle aggregation was involved in the hysteresis phenomena."}
{"id": "PMID:219892", "title": "Analysis of Dictyostelium discoideum plasma membrane fluidity by electron spin resonance.", "content": "Dictyostelium discoideum grown axenically in media containing polyunsaturated fatty acids exhibited normal growth rates but impaired differentiation (Weeks, G. (1976) Biochim. Biophys. Acta 450, 21--32). Since cell-cell contact is vital for differentiation but unnecessary for growth we have examined the isolated plasma membranes of these cells. The lipids of the plasma membranes of cells grown in the presence of polyunsaturated fatty acids contain considerable quantities of these acids, but the total phospholipid and sterol contents of the plasma membrane are close to normal. Electron spin resonance studies using 5-doxyl-stearic acid as the spin probe reveal two things. Firstly, there are no detectable characteristic transition temperatures in the plasma membranes of D. discoideum. Secondly, the plasma membranes of cell grown in the presence of polyunsaturated fatty acids have essentially the same fluidity as that of the control cells. The possible significance of this result to impaired cell-cell interaction is discussed.", "contents": "Analysis of Dictyostelium discoideum plasma membrane fluidity by electron spin resonance. Dictyostelium discoideum grown axenically in media containing polyunsaturated fatty acids exhibited normal growth rates but impaired differentiation (Weeks, G. (1976) Biochim. Biophys. Acta 450, 21--32). Since cell-cell contact is vital for differentiation but unnecessary for growth we have examined the isolated plasma membranes of these cells. The lipids of the plasma membranes of cells grown in the presence of polyunsaturated fatty acids contain considerable quantities of these acids, but the total phospholipid and sterol contents of the plasma membrane are close to normal. Electron spin resonance studies using 5-doxyl-stearic acid as the spin probe reveal two things. Firstly, there are no detectable characteristic transition temperatures in the plasma membranes of D. discoideum. Secondly, the plasma membranes of cell grown in the presence of polyunsaturated fatty acids have essentially the same fluidity as that of the control cells. The possible significance of this result to impaired cell-cell interaction is discussed."}
{"id": "PMID:219893", "title": "Disappearance of calcium-induced phase separation in phosphatidylserine-phosphatidylcholine membranes caused by protonation and by electric current.", "content": "Disappearance of Ca2+-induced phase separation in phosphatidylserine-phosphatidylcholine membrane has been studied under several conditions by monitoring electron spin resonance spectrum of spin-labeled phosphatidylcholine. The membranes were prepared in Millipore filters. Electron micrographs of the pre parations showed formation of multilayered structures lined on the pore surface. The phase separation was disappeared when the membrane was soaked in non-buffered salt solution (100 ml KCl, pH 5.5). It was markedly contrasting that when the bathing salt solution was buffered no disappearance was observed. Disappearance of the phase separation was also observed when the Ca2+-treated membrane was transferred to acidic salt solutions (less than or equal to pH 2.5) or to low ionic strength media (less than or equal to mM) buffered at pH 5.5, and then to the buffered salt solution (100 mM KCl, pH 5.5). These are due to replacement of Ca2+ by proton, proton-induced separation, followed by disappearance of the phase separation in the buffered salt solution. Biological significance of the competition between Ca2+ and proton for the phase separation or domain formation in the membranes was emphasized.", "contents": "Disappearance of calcium-induced phase separation in phosphatidylserine-phosphatidylcholine membranes caused by protonation and by electric current. Disappearance of Ca2+-induced phase separation in phosphatidylserine-phosphatidylcholine membrane has been studied under several conditions by monitoring electron spin resonance spectrum of spin-labeled phosphatidylcholine. The membranes were prepared in Millipore filters. Electron micrographs of the pre parations showed formation of multilayered structures lined on the pore surface. The phase separation was disappeared when the membrane was soaked in non-buffered salt solution (100 ml KCl, pH 5.5). It was markedly contrasting that when the bathing salt solution was buffered no disappearance was observed. Disappearance of the phase separation was also observed when the Ca2+-treated membrane was transferred to acidic salt solutions (less than or equal to pH 2.5) or to low ionic strength media (less than or equal to mM) buffered at pH 5.5, and then to the buffered salt solution (100 mM KCl, pH 5.5). These are due to replacement of Ca2+ by proton, proton-induced separation, followed by disappearance of the phase separation in the buffered salt solution. Biological significance of the competition between Ca2+ and proton for the phase separation or domain formation in the membranes was emphasized."}
{"id": "PMID:219895", "title": "The purification of nuclease-free T4-RNA ligase.", "content": "RNA ligase has been highly purified in good yields from bacteriophage T4-infected Escherichia coli by a rapid and reproducible procedure. The enzyme is free of phosphomonoesterase and ribonuclease activities and is therefore suitable for the synthesis of oligoribonucleotides and for the labeling of the 3'-terminus of RNA. Greater than 90% of the protein in the enzyme preparation migrates as a single band on gradient polyacrylamide gels containing sodium dodecyl sulfate during electrophoresis. For use as a DNA synthesis reagent the enzyme may be reliably freed of deoxyribonuclease activity by an additional chromatographic procedure using a commercially avialable resin.", "contents": "The purification of nuclease-free T4-RNA ligase. RNA ligase has been highly purified in good yields from bacteriophage T4-infected Escherichia coli by a rapid and reproducible procedure. The enzyme is free of phosphomonoesterase and ribonuclease activities and is therefore suitable for the synthesis of oligoribonucleotides and for the labeling of the 3'-terminus of RNA. Greater than 90% of the protein in the enzyme preparation migrates as a single band on gradient polyacrylamide gels containing sodium dodecyl sulfate during electrophoresis. For use as a DNA synthesis reagent the enzyme may be reliably freed of deoxyribonuclease activity by an additional chromatographic procedure using a commercially avialable resin."}
{"id": "PMID:219894", "title": "Dimethyl-10,12-benz(a)acridine; evidence for differential effects on the synthesis of RNA of mammalian or avian fibroblasts and some RNA viruses.", "content": "We have studied the differential effect of dimethyl-10,12-benz(a)acridine (DBMAcr) on the synthesis of RNA of chicken or mouse fibroblasts in culture and that of some RNA-containing viruses such as Rous sarcoma virus and Mengovirus. DMBAcr at low concentrations blocks the cell multiplication of both normal and Rous sarcoma virus-transformed chicken fibroblasts in culture; it affects transformed cells more than normal ones. The cell growth inhibiting effect of DMBAcr is reversible after short periods of incubation. DMBAcr depresses the synthesis of cellular DNA and RNA in parallel. Concurrently the synthesis of protein proceedes at a relatively high rate in DMBAcr-treated cultures. Its inhibitory effect on cellular RNA synthesis is mostly due to a block in the formation of 28 S and 18 S ribosomal RNA species; in contrast, the synthesis of 45 S ribosomal RNA precursor is proceeding at almost control rate. Also, the synthesis of heterogeneous nuclear RNA is not blocked by DMBAcr. The production of Rous sarcoma virus in transformed fibroblasts is not affected by DMBAcr. Since this is correlated with persisting high rates of protein and heterogenous nuclear RNA synthesis, the effects of DMBAcr suggest that the synthesis of Rous sarcoma virus-RNA shares the specificity of messenger and heterogeneous nuclear RNA. DMBAcr inhibits the synthesis of viral RNA of Mengovirus under conditions where the synthesis of total cellular RNA is not appreciably depressed, suggesting its differential effect on the DNA-directed and the RNA-directed RNA synthesis.", "contents": "Dimethyl-10,12-benz(a)acridine; evidence for differential effects on the synthesis of RNA of mammalian or avian fibroblasts and some RNA viruses. We have studied the differential effect of dimethyl-10,12-benz(a)acridine (DBMAcr) on the synthesis of RNA of chicken or mouse fibroblasts in culture and that of some RNA-containing viruses such as Rous sarcoma virus and Mengovirus. DMBAcr at low concentrations blocks the cell multiplication of both normal and Rous sarcoma virus-transformed chicken fibroblasts in culture; it affects transformed cells more than normal ones. The cell growth inhibiting effect of DMBAcr is reversible after short periods of incubation. DMBAcr depresses the synthesis of cellular DNA and RNA in parallel. Concurrently the synthesis of protein proceedes at a relatively high rate in DMBAcr-treated cultures. Its inhibitory effect on cellular RNA synthesis is mostly due to a block in the formation of 28 S and 18 S ribosomal RNA species; in contrast, the synthesis of 45 S ribosomal RNA precursor is proceeding at almost control rate. Also, the synthesis of heterogeneous nuclear RNA is not blocked by DMBAcr. The production of Rous sarcoma virus in transformed fibroblasts is not affected by DMBAcr. Since this is correlated with persisting high rates of protein and heterogenous nuclear RNA synthesis, the effects of DMBAcr suggest that the synthesis of Rous sarcoma virus-RNA shares the specificity of messenger and heterogeneous nuclear RNA. DMBAcr inhibits the synthesis of viral RNA of Mengovirus under conditions where the synthesis of total cellular RNA is not appreciably depressed, suggesting its differential effect on the DNA-directed and the RNA-directed RNA synthesis."}
{"id": "PMID:219898", "title": "The absence of a role for the carbohydrate moiety in the binding of apolipoprotein B to the low density lipoprotein receptor.", "content": "The binding of low density lipoprotein (LDL) to fibroblasts occurs through apolipoprotein B, a glycoprotein. The role of the carbohydrate in binding was assessed in two ways: (1) LDL, freed of sialic acid and most of the glucosamine and hexoses by digestion with a mixture of glycosidases, bound to fibroblasts as does native LDL. (2) The glycopeptides liberated from apoprotein B by trypsin and pronase failed to inhibit LDL binding to fibroblasts. Apparently the carbohydrate moiety of LDL does not interact with the plasma membrane receptor.", "contents": "The absence of a role for the carbohydrate moiety in the binding of apolipoprotein B to the low density lipoprotein receptor. The binding of low density lipoprotein (LDL) to fibroblasts occurs through apolipoprotein B, a glycoprotein. The role of the carbohydrate in binding was assessed in two ways: (1) LDL, freed of sialic acid and most of the glucosamine and hexoses by digestion with a mixture of glycosidases, bound to fibroblasts as does native LDL. (2) The glycopeptides liberated from apoprotein B by trypsin and pronase failed to inhibit LDL binding to fibroblasts. Apparently the carbohydrate moiety of LDL does not interact with the plasma membrane receptor."}
{"id": "PMID:219899", "title": "Adenosine 3',5'-monophosphate-dependent protein kinase(s) in diploid and SV40 transformed human fibroblasts.", "content": "Cyclic AMP-dependent protein kinases (EC 2.7.1.37; ATP:protein phosphotransferase) in the human diploid fibroblast WI-38 and an SV40-transformant WI-38-VA13-2RA (VA13) have been compared on the basis of their concentrations in cells, isoenzyme composition and susceptibility to hormonal activation. In high population density cultures, total soluble cyclic AMP-dependent kinase activities measured with histone were essentially the same in WI-38 and VA13. Two soluble protein kinase forms separated by chromatography on DEAE-cellulose were present in both cell lines. The concentration of cyclic AMP required for half-maximal activation of both enzyme forms was 10-30 nM. Overall kinase stimulation was greater for the Peak I enzymes. Kinase activation induced in the presence of 0.5 M KCl was more rapid and complete for the Peak I enzymes. Under conditions which elevated the concentration of cyclic AMP in WI-38 and VA13 cells the activities of the soluble histone kinases were increased. Incubation of the cells with either of 5.7 micronM prostaglandin E1 or 1 micronM isopropylnorepinephrine induced complete activation of the cyclic AMP-dependent histone kinases within 5 min and maintained the effect for 20 min. When intracellular cyclic AMP levels were raised by prostaglandin E1, activation of glycogen phosphorylase (assayed-AMP) suggested that this enzyme cascade involving cyclic AMP-dependent protein kinase(s) was intact and responsive in both cell lines.", "contents": "Adenosine 3',5'-monophosphate-dependent protein kinase(s) in diploid and SV40 transformed human fibroblasts. Cyclic AMP-dependent protein kinases (EC 2.7.1.37; ATP:protein phosphotransferase) in the human diploid fibroblast WI-38 and an SV40-transformant WI-38-VA13-2RA (VA13) have been compared on the basis of their concentrations in cells, isoenzyme composition and susceptibility to hormonal activation. In high population density cultures, total soluble cyclic AMP-dependent kinase activities measured with histone were essentially the same in WI-38 and VA13. Two soluble protein kinase forms separated by chromatography on DEAE-cellulose were present in both cell lines. The concentration of cyclic AMP required for half-maximal activation of both enzyme forms was 10-30 nM. Overall kinase stimulation was greater for the Peak I enzymes. Kinase activation induced in the presence of 0.5 M KCl was more rapid and complete for the Peak I enzymes. Under conditions which elevated the concentration of cyclic AMP in WI-38 and VA13 cells the activities of the soluble histone kinases were increased. Incubation of the cells with either of 5.7 micronM prostaglandin E1 or 1 micronM isopropylnorepinephrine induced complete activation of the cyclic AMP-dependent histone kinases within 5 min and maintained the effect for 20 min. When intracellular cyclic AMP levels were raised by prostaglandin E1, activation of glycogen phosphorylase (assayed-AMP) suggested that this enzyme cascade involving cyclic AMP-dependent protein kinase(s) was intact and responsive in both cell lines."}
{"id": "PMID:219900", "title": "Alpha- and beta-adrenergic receptors of the rat salivary gland. Elevation after chemical sympathectomy.", "content": "Binding of [3H]dihydroergokryptine and [3H]dihydroalprenolol to membrane preparations from rat submaxillary gland was measured to characterize the alpha- and beta-adrenergic receptors, respectively. Kinetic analysis of the data revealed a high affinity binding site for each radioligand. Inhibition of binding at each site was stereospecific for the active isomer of the catecholamine used. The greater ability of a beta1 than beta2 specific beta-adrenergic antagonist to displace [3H]dihydroalprenolol binding indicated that this binding site was of the beta1 type. Chemical sympathectomy with reserpine or 6-hydroxydopamine resulted in a significant increase in both [3H]dihydroalprenolol and [3H]dihydroergokryptine binding in the rat submaxillary gland. 3scatchard analysis of the data indicated that these increases in binding were due to a change in total number of binding sites for [3H]dihydroergokryptine and [3H]dihydroalprenolol with little change in apparent affinities. This suggests that changes in alpha- and beta-adrenergic receptor density may be important in the development of supersensitivity in salivary glands after reserpine and 6-hydroxydopamine treatment.", "contents": "Alpha- and beta-adrenergic receptors of the rat salivary gland. Elevation after chemical sympathectomy. Binding of [3H]dihydroergokryptine and [3H]dihydroalprenolol to membrane preparations from rat submaxillary gland was measured to characterize the alpha- and beta-adrenergic receptors, respectively. Kinetic analysis of the data revealed a high affinity binding site for each radioligand. Inhibition of binding at each site was stereospecific for the active isomer of the catecholamine used. The greater ability of a beta1 than beta2 specific beta-adrenergic antagonist to displace [3H]dihydroalprenolol binding indicated that this binding site was of the beta1 type. Chemical sympathectomy with reserpine or 6-hydroxydopamine resulted in a significant increase in both [3H]dihydroalprenolol and [3H]dihydroergokryptine binding in the rat submaxillary gland. 3scatchard analysis of the data indicated that these increases in binding were due to a change in total number of binding sites for [3H]dihydroergokryptine and [3H]dihydroalprenolol with little change in apparent affinities. This suggests that changes in alpha- and beta-adrenergic receptor density may be important in the development of supersensitivity in salivary glands after reserpine and 6-hydroxydopamine treatment."}
{"id": "PMID:219901", "title": "Bone matrix studies. Influences of parathyroid extract, calcitonin, and cholecalciferol and of rickets and its treatment.", "content": "Bones from young rats were incubated with radioactive glucosamine and proline. The concentrations and specific activities of matrix glycosaminoglycan fractions, prepared by a cetylpyridinium chloride method, and the specific activity of insoluble collagen hydroxyproline were determined. Acute parathyroid extract treatment increased labelling of hyaluronic acid and a glycopeptide fraction. These effects were partially blocked by calcitonin treatment which had no effect by itself. Parathyroid extract inhibited collagen synthesis and this effect was not blocked by calcitonin. Effects of these two hormones on labelling of chondroitin sulfate fractions were more variable. Vitamin D-3 caused an increase in labelling of all matrix fractions measured in bone from thyroparathyroidectomized rats, but its stimulating effect upon collagen synthesis was blocked by parathyroid extract. Bones from rats made rachitic on a phosphorus and vitamin D-deficient diet were incubated in vitro with radioactive glucosamine and proline. Over a three-week period rachitic bone exhibited a progressive fall in concentration and labelling of a glycopeptide-hyaluronic acid fraction, while pair-fed animals supplemented either with phosphorus alone or with phosphorus and vitamin D-3 not only remineralized their bones, but the bones showed a pronounced increment in concentration and labelling of this fraction. Both treatment regimens also enhanced chondroitin sulfate and collagen labelling.", "contents": "Bone matrix studies. Influences of parathyroid extract, calcitonin, and cholecalciferol and of rickets and its treatment. Bones from young rats were incubated with radioactive glucosamine and proline. The concentrations and specific activities of matrix glycosaminoglycan fractions, prepared by a cetylpyridinium chloride method, and the specific activity of insoluble collagen hydroxyproline were determined. Acute parathyroid extract treatment increased labelling of hyaluronic acid and a glycopeptide fraction. These effects were partially blocked by calcitonin treatment which had no effect by itself. Parathyroid extract inhibited collagen synthesis and this effect was not blocked by calcitonin. Effects of these two hormones on labelling of chondroitin sulfate fractions were more variable. Vitamin D-3 caused an increase in labelling of all matrix fractions measured in bone from thyroparathyroidectomized rats, but its stimulating effect upon collagen synthesis was blocked by parathyroid extract. Bones from rats made rachitic on a phosphorus and vitamin D-deficient diet were incubated in vitro with radioactive glucosamine and proline. Over a three-week period rachitic bone exhibited a progressive fall in concentration and labelling of a glycopeptide-hyaluronic acid fraction, while pair-fed animals supplemented either with phosphorus alone or with phosphorus and vitamin D-3 not only remineralized their bones, but the bones showed a pronounced increment in concentration and labelling of this fraction. Both treatment regimens also enhanced chondroitin sulfate and collagen labelling."}
{"id": "PMID:219902", "title": "[Spike transmission in statistical neuronal ensembles. Induced epileptic focus in a model of hippocampal field CA3].", "content": "In a spatially heterogeneous model the transition to supercritical phase was investigated as to the parameter characterizing the activation level of the pyramidal cells related to one another assuming the nonuniformity radius to be R0 = const. This is a transition from spontaneous activity to epileptoid bursts. Before the onset of epileptoid bursts the region of stochastic nonequilibrium of solutions is developed likely to produce pathologic dynamic patterns. With further increase of the activation parameter the system comes to epileptoid state. This synchronized firing of pyramidal cells is accompanied with phases of inhibition. A decrease in the nonuniformity radius leads to the formation of an epileptic focus. It is a dissipative structure. The evolution of it is not further followed, since the transport equations do not include its dynamics.", "contents": "[Spike transmission in statistical neuronal ensembles. Induced epileptic focus in a model of hippocampal field CA3]. In a spatially heterogeneous model the transition to supercritical phase was investigated as to the parameter characterizing the activation level of the pyramidal cells related to one another assuming the nonuniformity radius to be R0 = const. This is a transition from spontaneous activity to epileptoid bursts. Before the onset of epileptoid bursts the region of stochastic nonequilibrium of solutions is developed likely to produce pathologic dynamic patterns. With further increase of the activation parameter the system comes to epileptoid state. This synchronized firing of pyramidal cells is accompanied with phases of inhibition. A decrease in the nonuniformity radius leads to the formation of an epileptic focus. It is a dissipative structure. The evolution of it is not further followed, since the transport equations do not include its dynamics."}
{"id": "PMID:219904", "title": "[Molar extinction of pigment in the reaction center of photosystem II chloroplasts].", "content": "The absolute spin number in the Photosystem I chloroplast fragments from Vicia faba plant photooxidized in the presence of silicomolybdate has been carefully measured by means of camparison of ESR signals of P680-centers and of nitroxyl free radical aqueous solution. The data obtained together with simultaneous measurement of light-induced bleaching centered at 680 nm have been used to determine the molar extinction of reduced P680-center epsilon680 = 0.66 . 10(5) M-1 cm-1.", "contents": "[Molar extinction of pigment in the reaction center of photosystem II chloroplasts]. The absolute spin number in the Photosystem I chloroplast fragments from Vicia faba plant photooxidized in the presence of silicomolybdate has been carefully measured by means of camparison of ESR signals of P680-centers and of nitroxyl free radical aqueous solution. The data obtained together with simultaneous measurement of light-induced bleaching centered at 680 nm have been used to determine the molar extinction of reduced P680-center epsilon680 = 0.66 . 10(5) M-1 cm-1."}
{"id": "PMID:219905", "title": "[Study of the transmembrane potential of mitochondria using cyanine dyes].", "content": "Changes in fluorescent intensity of cyanine dyes dis-C3-(5) and dis-C2-(5) were measured in suspension of rat liver mitochondria upon the development of the energized state by adding succinate or ATP. It has been shown that these dyes possess a rotenone-like effect but they do not damage the inner mitochondrial membrane. The data on ATP synthesis and Ca2+ transport correspond to the basic aspects of the chemiosmotic conception.", "contents": "[Study of the transmembrane potential of mitochondria using cyanine dyes]. Changes in fluorescent intensity of cyanine dyes dis-C3-(5) and dis-C2-(5) were measured in suspension of rat liver mitochondria upon the development of the energized state by adding succinate or ATP. It has been shown that these dyes possess a rotenone-like effect but they do not damage the inner mitochondrial membrane. The data on ATP synthesis and Ca2+ transport correspond to the basic aspects of the chemiosmotic conception."}
{"id": "PMID:219910", "title": "Amino acid sequence of rat thymus histone H2B and identification of the in vitro phosphorylation sites.", "content": "The amino acid sequence of rat thymus histone obtained in highly purified form by preparative electrophoresis, was determined. This sequence is identical to the sequence of calf thymus histone H2B. The in vitro phosphorylation of the rat histone with a cyclic AMP-dependent protein kinase isolated from rat pancreas led to the identification of four sites of phosphorylation: two major ones, at serine residues 32 and 36, and two minor ones, specific of the rat protein kinase, at serine residues 87 and 91.", "contents": "Amino acid sequence of rat thymus histone H2B and identification of the in vitro phosphorylation sites. The amino acid sequence of rat thymus histone obtained in highly purified form by preparative electrophoresis, was determined. This sequence is identical to the sequence of calf thymus histone H2B. The in vitro phosphorylation of the rat histone with a cyclic AMP-dependent protein kinase isolated from rat pancreas led to the identification of four sites of phosphorylation: two major ones, at serine residues 32 and 36, and two minor ones, specific of the rat protein kinase, at serine residues 87 and 91."}
{"id": "PMID:219911", "title": "Studies of the plasma membrane during maturation of the mammalian erythrocyte.", "content": "Plasma membranes were obtained from a homogeneous population of rabbit red blood cells at different maturation periods. Minor modifications in membrane proteins and membrane phospholipids and significant decreases in membrane glycoproteins and total lipids were observed with the age of the cell. The ouabain inhibited (Na+K+)-ATPase and the adenylate cyclase decreased with maturation but acetylcholinesterase and 5'-nucleotidase remained almost unchanged. The apparent activation energy of the ATPase increased with maturation. The results indicate that structural and functional modifications of the plasma membrane occur concomitantly with the ageing processes of the red cell.", "contents": "Studies of the plasma membrane during maturation of the mammalian erythrocyte. Plasma membranes were obtained from a homogeneous population of rabbit red blood cells at different maturation periods. Minor modifications in membrane proteins and membrane phospholipids and significant decreases in membrane glycoproteins and total lipids were observed with the age of the cell. The ouabain inhibited (Na+K+)-ATPase and the adenylate cyclase decreased with maturation but acetylcholinesterase and 5'-nucleotidase remained almost unchanged. The apparent activation energy of the ATPase increased with maturation. The results indicate that structural and functional modifications of the plasma membrane occur concomitantly with the ageing processes of the red cell."}
{"id": "PMID:219912", "title": "[Cardiotropic effects of luliberin. Effects of luliberin on the activities of phosphorylase A and ornithine decarboxylase and concentration of 3', 5'-AMP].", "content": "The level of luliberin, the luteinizing hormone-releasing hormone (LH-RH), and the possibility of the hormonal control of metabolic and biosynthetic processes in the heart were studied. It was shown that the rat heart contains a factor, which is immunochemically and chromatographically related to LH-RH (19--46 picograms per organ). Intraperitoneal injection of LH-RH increases the activities of phosphorylase A and ornithine decarboxylase and the concentration of 3',5'-AMP and potentiates the stimulating effect of adrenaline on ornithine decarboxylase.", "contents": "[Cardiotropic effects of luliberin. Effects of luliberin on the activities of phosphorylase A and ornithine decarboxylase and concentration of 3', 5'-AMP]. The level of luliberin, the luteinizing hormone-releasing hormone (LH-RH), and the possibility of the hormonal control of metabolic and biosynthetic processes in the heart were studied. It was shown that the rat heart contains a factor, which is immunochemically and chromatographically related to LH-RH (19--46 picograms per organ). Intraperitoneal injection of LH-RH increases the activities of phosphorylase A and ornithine decarboxylase and the concentration of 3',5'-AMP and potentiates the stimulating effect of adrenaline on ornithine decarboxylase."}
{"id": "PMID:219908", "title": "[Effect of linoleic acid and products of its free radical oxidation on succinate dehydrogenase].", "content": "Effects of linoleic acid and its oxidation products (with 75--80% content of hydroperoxide) on isolated succinate dehydrogenase were studied by means of spectrophotometry and ESR-spectroscopy. It was shown that unlike the unoxidized acid, low concentrations of its oxidation products increased catalytic activity, while its high concentrations of its oxidation products increased catalytic activity, while its high concentrations brought about a decrease of SH-group content and the amplitude of ESR signal of reduced nonheme iron in the enzyme.", "contents": "[Effect of linoleic acid and products of its free radical oxidation on succinate dehydrogenase]. Effects of linoleic acid and its oxidation products (with 75--80% content of hydroperoxide) on isolated succinate dehydrogenase were studied by means of spectrophotometry and ESR-spectroscopy. It was shown that unlike the unoxidized acid, low concentrations of its oxidation products increased catalytic activity, while its high concentrations of its oxidation products increased catalytic activity, while its high concentrations brought about a decrease of SH-group content and the amplitude of ESR signal of reduced nonheme iron in the enzyme."}
{"id": "PMID:219913", "title": "[Conformational isomerization of lactate dehydrogenase complexes formed by pyruvate and coenzyme analogs].", "content": "The kinetics of LDH-catalyzed reduction of pyruvate involving APADH were studied. It was shown that under conditions of a single turnover reaction the first order rate constant is equal to 37+/-4 sec-1. The reaction rate (vo) did not change when a deutero-coenzyme was used. The relationship between vo and pyruvate concentration is hyperbolic. It is concluded that isomerization of the ternary LDH-APADH-pyruvate complex limits the reaction rate. The spectral properties and the kinetics of formation and dissociation of abortive LDH complexes with pyruvate and NAD analogs (APAD and PAAD) were studied. The participation of the carboxamide group of NAD in conformational isomerization of the LDH-NADH-pyruvate and LDH-NAD-pyruvate complexes was studied.", "contents": "[Conformational isomerization of lactate dehydrogenase complexes formed by pyruvate and coenzyme analogs]. The kinetics of LDH-catalyzed reduction of pyruvate involving APADH were studied. It was shown that under conditions of a single turnover reaction the first order rate constant is equal to 37+/-4 sec-1. The reaction rate (vo) did not change when a deutero-coenzyme was used. The relationship between vo and pyruvate concentration is hyperbolic. It is concluded that isomerization of the ternary LDH-APADH-pyruvate complex limits the reaction rate. The spectral properties and the kinetics of formation and dissociation of abortive LDH complexes with pyruvate and NAD analogs (APAD and PAAD) were studied. The participation of the carboxamide group of NAD in conformational isomerization of the LDH-NADH-pyruvate and LDH-NAD-pyruvate complexes was studied."}
{"id": "PMID:219914", "title": "[Peculiarities of phosphorylation of skeletal muscle troponin under some forms muscle pathologies].", "content": "Phosphorylation of rat and rabbit troponin from normal skeletal muscles and from skeletal muscles of animals under avitaminosis, denervation and hypokinesia was studied. Phosphorylation was carried out by cAMP-dependent protein kinase with [gamma-33P] as substrate. The incorporation of labelled phosphorus into troponin T of the damaged muscles was decreased as compared to normal. After preliminary dephosphorylation of troponin by alkaline phosphatase immobilized on Sepharose 4B, the ability of damaged muscle troponin for subsequent phosphorylation was also decreased as compared to the control. It may be thus assumed that there exist conformational changes of troponin under muscular system pathologies.", "contents": "[Peculiarities of phosphorylation of skeletal muscle troponin under some forms muscle pathologies]. Phosphorylation of rat and rabbit troponin from normal skeletal muscles and from skeletal muscles of animals under avitaminosis, denervation and hypokinesia was studied. Phosphorylation was carried out by cAMP-dependent protein kinase with [gamma-33P] as substrate. The incorporation of labelled phosphorus into troponin T of the damaged muscles was decreased as compared to normal. After preliminary dephosphorylation of troponin by alkaline phosphatase immobilized on Sepharose 4B, the ability of damaged muscle troponin for subsequent phosphorylation was also decreased as compared to the control. It may be thus assumed that there exist conformational changes of troponin under muscular system pathologies."}
{"id": "PMID:219915", "title": "[Interrelationship between metabolic and genetic regulation of alkaline phosphatase and poly- and pyrophosphatases].", "content": "The effects of orthophosphate and mutations in the regulatory genes of alkaline phosphatase on the activities of pyrophosphatase and polyphosphatase of E. coli were studied. It was shown that orthophosphate represses the synthesis of alkaline phosphatase as well as that of polyphosphatase without having any effect on pyrophosphatase. The genes phoR and phoS are involved in the formation of a repressory complex both for alkaline phosphatase and polyphosphatase. The gene phoT is probably involved in a partial repression of pyrophosphatase synthesis.", "contents": "[Interrelationship between metabolic and genetic regulation of alkaline phosphatase and poly- and pyrophosphatases]. The effects of orthophosphate and mutations in the regulatory genes of alkaline phosphatase on the activities of pyrophosphatase and polyphosphatase of E. coli were studied. It was shown that orthophosphate represses the synthesis of alkaline phosphatase as well as that of polyphosphatase without having any effect on pyrophosphatase. The genes phoR and phoS are involved in the formation of a repressory complex both for alkaline phosphatase and polyphosphatase. The gene phoT is probably involved in a partial repression of pyrophosphatase synthesis."}
{"id": "PMID:219916", "title": "[Mechanism of catalysis by o-diphenol oxidase].", "content": "The reaction of terminal oxidation of the substrate (catechol) by molecular oxygen catalyzed by o-diphenoloxidase (o-diphenol: oxygen oxydoreductase; EC 1.10.3.1) is found to occur via a free radical mechanism. The copper of the active center changes its valency during the reaction. The spectra of substrate radicals and of the Cu2+ ions were registered by means of a high sensitivity ESR-spectrometer and their concentrations were determined.", "contents": "[Mechanism of catalysis by o-diphenol oxidase]. The reaction of terminal oxidation of the substrate (catechol) by molecular oxygen catalyzed by o-diphenoloxidase (o-diphenol: oxygen oxydoreductase; EC 1.10.3.1) is found to occur via a free radical mechanism. The copper of the active center changes its valency during the reaction. The spectra of substrate radicals and of the Cu2+ ions were registered by means of a high sensitivity ESR-spectrometer and their concentrations were determined."}
{"id": "PMID:219917", "title": "Deacylation-reacylation of phospholipids by rat embryos and their associated placentas. I. Placental acyltransferase.", "content": "Homogenates and subcellular fractions of rat chorioallantoic placentas obtained on the 14th day of gestation were assayed for acyl-CoA: lysophospholipid acyltransferase activities using (14C)-linoleic acid, ATP, and CoA, or (14C)-oleoyl-CoA as acyl donor and 1-acylglycerophosphorylcholine or 1-acylglycerophosphorylethanolamine as acyl acceptor. We found that: (1) the Lands' deacylation-reacylation cycle is present in the rat placenta, (2) the enzymes were concentrated in the microsomal fraction, and (3) the optimal conditions for in vitro assay of those enzyme activities were similar to those reported for adult tissues. Comparison of the acyl composition of phospholipids in maternal blood with those in placental homogenates revealed similarities which are consistent with a role for this cycle in vivo in placental uptake of phospholipids. That this cycle may function also in placental transformation of phospholipids in vivo, is suggested by differences between the acyl composition of phospholipids in placental homogenates and microsomal fractions.", "contents": "Deacylation-reacylation of phospholipids by rat embryos and their associated placentas. I. Placental acyltransferase. Homogenates and subcellular fractions of rat chorioallantoic placentas obtained on the 14th day of gestation were assayed for acyl-CoA: lysophospholipid acyltransferase activities using (14C)-linoleic acid, ATP, and CoA, or (14C)-oleoyl-CoA as acyl donor and 1-acylglycerophosphorylcholine or 1-acylglycerophosphorylethanolamine as acyl acceptor. We found that: (1) the Lands' deacylation-reacylation cycle is present in the rat placenta, (2) the enzymes were concentrated in the microsomal fraction, and (3) the optimal conditions for in vitro assay of those enzyme activities were similar to those reported for adult tissues. Comparison of the acyl composition of phospholipids in maternal blood with those in placental homogenates revealed similarities which are consistent with a role for this cycle in vivo in placental uptake of phospholipids. That this cycle may function also in placental transformation of phospholipids in vivo, is suggested by differences between the acyl composition of phospholipids in placental homogenates and microsomal fractions."}
{"id": "PMID:219919", "title": "Large-scale isolation of equine liver alcohol dehydrogenase on a blue agarose gel.", "content": "Equine liver alcohol dehydrogenase (EC 1.1.1.1) has been purified by a new scheme using a blue agarose gel (Blue Sepharose) as an affinity sorbent. Starting amounts of 0.6 to 10 kg liver have been processed to enzyme possessing 1.5 U/mg average specific activity, in about three to four days. Some parameters concernining adsorption of enzyme to the blue gel as well as recovery therefrom have been explored.", "contents": "Large-scale isolation of equine liver alcohol dehydrogenase on a blue agarose gel. Equine liver alcohol dehydrogenase (EC 1.1.1.1) has been purified by a new scheme using a blue agarose gel (Blue Sepharose) as an affinity sorbent. Starting amounts of 0.6 to 10 kg liver have been processed to enzyme possessing 1.5 U/mg average specific activity, in about three to four days. Some parameters concernining adsorption of enzyme to the blue gel as well as recovery therefrom have been explored."}
{"id": "PMID:219920", "title": "Preparation and properties of an immobilized derivative of penicillinase.", "content": "Penicillinase (beta-lactamase I, EC 3.5.2.6) secreted by Bacillus cereus, strain 569/H, was covalently attached to aminoethyl cellulose via glutaraldehyde. The immobilized derivative shows increased thermostability and decreased susceptibility to conformational changes induced by certain substrates of penicillinase. The decline in the rate of hydrolysis of such substrates was consequently suppressed by immobilization. A marked increase in Km was observed with all substrates except for the unsubstituted 6-aminopenicillanic acid. The altered properties of the new derivative are attributed to the constraint imposed by immobilization on the conformational flexibility of the enzyme molecule. Thus, apart from obvious technological interest, immobilized penicillinase provides a useful model for the study of the role of flexibility in the function of an enzyme.", "contents": "Preparation and properties of an immobilized derivative of penicillinase. Penicillinase (beta-lactamase I, EC 3.5.2.6) secreted by Bacillus cereus, strain 569/H, was covalently attached to aminoethyl cellulose via glutaraldehyde. The immobilized derivative shows increased thermostability and decreased susceptibility to conformational changes induced by certain substrates of penicillinase. The decline in the rate of hydrolysis of such substrates was consequently suppressed by immobilization. A marked increase in Km was observed with all substrates except for the unsubstituted 6-aminopenicillanic acid. The altered properties of the new derivative are attributed to the constraint imposed by immobilization on the conformational flexibility of the enzyme molecule. Thus, apart from obvious technological interest, immobilized penicillinase provides a useful model for the study of the role of flexibility in the function of an enzyme."}
{"id": "PMID:219921", "title": "[Changes in the proliferative response of human lymphocytes in vitro on exposure to subcellular components of Bordetella pertussis].", "content": "Different components of B. pertussis were found to have a similar inhibitory effect on thymidine-3H incorporation caused by phytohemagglutinin (PHA) in the culture of lymphocytes taken from donors immunized with tetanus toxoid. However, the same fractions of B. pertussis produced differential effects on the reaction of lymphocyte proliferation in response to tetanus toxoid: murein-\"ontaining membranes enhanced thymidine-3H incorporation, RNA-containing fractions reduced it and water-soluble components of disintegrated B. pertussis produced no effect on lymphocyte proliferation.", "contents": "[Changes in the proliferative response of human lymphocytes in vitro on exposure to subcellular components of Bordetella pertussis]. Different components of B. pertussis were found to have a similar inhibitory effect on thymidine-3H incorporation caused by phytohemagglutinin (PHA) in the culture of lymphocytes taken from donors immunized with tetanus toxoid. However, the same fractions of B. pertussis produced differential effects on the reaction of lymphocyte proliferation in response to tetanus toxoid: murein-\"ontaining membranes enhanced thymidine-3H incorporation, RNA-containing fractions reduced it and water-soluble components of disintegrated B. pertussis produced no effect on lymphocyte proliferation."}
{"id": "PMID:219923", "title": "Glucocorticoid effects on peripheral blood lymphocytes in cows infected with bovine leukemia virus.", "content": "We examined the effects of glucocorticoids on peripheral blood lymphocytes (PBL) in lymphoproliferative conditions associated with bovine leukemia virus (BLV): persistent lymphocytosis (PL) and lymphosarcoma cell leukemia (BLSL). The effects of hydrocortisone 21-sodium succinate (HSS) on spontaneous incorporation (SI) and mitogen-stimulated incorporation of radiolabeled-thymidine and the effects of intramuscular administration of prednisolone acetate were studied. An expanded population of B lymphocytes in cows with PL was remarkable sensitive to glucocorticoids in vitro and in vivo. SI was markedly inhibited by concentrations of HSS as low as 10(-7) M. These results correlated well with in vivo observations, where an 80%-90% decrease in PBL occurred during the course of glucocorticoid administration. The decrease in total lymphocytes was accounted for almost entirely by a decrease in the expanded B lymphocyte population. Steroid-sensitive lymphocytes together with steroid-resistant cells were observed in cows with BLSL. The reduction in the steroid-sensitive lymphocytes was associated with rapid disease progression in cows with lymphosarcoma. Steroid-sensitive lymphocyte populations in cows with BLSL may include the same reactive B-cell population found in cows with PL. Glucocorticoids may prove to be a useful tool for study of the immune response to the oncogenic virus and lymphoma in BLV-infected cattle.", "contents": "Glucocorticoid effects on peripheral blood lymphocytes in cows infected with bovine leukemia virus. We examined the effects of glucocorticoids on peripheral blood lymphocytes (PBL) in lymphoproliferative conditions associated with bovine leukemia virus (BLV): persistent lymphocytosis (PL) and lymphosarcoma cell leukemia (BLSL). The effects of hydrocortisone 21-sodium succinate (HSS) on spontaneous incorporation (SI) and mitogen-stimulated incorporation of radiolabeled-thymidine and the effects of intramuscular administration of prednisolone acetate were studied. An expanded population of B lymphocytes in cows with PL was remarkable sensitive to glucocorticoids in vitro and in vivo. SI was markedly inhibited by concentrations of HSS as low as 10(-7) M. These results correlated well with in vivo observations, where an 80%-90% decrease in PBL occurred during the course of glucocorticoid administration. The decrease in total lymphocytes was accounted for almost entirely by a decrease in the expanded B lymphocyte population. Steroid-sensitive lymphocytes together with steroid-resistant cells were observed in cows with BLSL. The reduction in the steroid-sensitive lymphocytes was associated with rapid disease progression in cows with lymphosarcoma. Steroid-sensitive lymphocyte populations in cows with BLSL may include the same reactive B-cell population found in cows with PL. Glucocorticoids may prove to be a useful tool for study of the immune response to the oncogenic virus and lymphoma in BLV-infected cattle."}
{"id": "PMID:219925", "title": "Influence of malathion (O,O'-dimethyl dithiophosphate of diethyl mercaptosuccinate) on body enzymes in dermal subacute toxicity studies in Bubalus bubalis species.", "content": "The effect of daily dermal spray of malathion for four weeks in recommended (0.5 and 1.0 per cent) and higher (5.0 per cent) concentration on various enzymes in Bubalus bubalis species were studied. The higher concentration of 5.0 per cent showed lethal effect after 2 to 3 exposures. The cholinesterase activity in both RBC (RChE) and plasma (PChE) were inhibited with all the concentrations. There was also significant (P less than 0.05) elevation in the activities of serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase with 1.0 and 5.0 per cent spray and enzyme activities remained altered even during post-medication. The extent of various biochemical changes were dose and time dependent.", "contents": "Influence of malathion (O,O'-dimethyl dithiophosphate of diethyl mercaptosuccinate) on body enzymes in dermal subacute toxicity studies in Bubalus bubalis species. The effect of daily dermal spray of malathion for four weeks in recommended (0.5 and 1.0 per cent) and higher (5.0 per cent) concentration on various enzymes in Bubalus bubalis species were studied. The higher concentration of 5.0 per cent showed lethal effect after 2 to 3 exposures. The cholinesterase activity in both RBC (RChE) and plasma (PChE) were inhibited with all the concentrations. There was also significant (P less than 0.05) elevation in the activities of serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase with 1.0 and 5.0 per cent spray and enzyme activities remained altered even during post-medication. The extent of various biochemical changes were dose and time dependent."}
{"id": "PMID:219926", "title": "Effects of concanavalin A on 5-hydroxytryptamine uptake by rabbit blood platelets and on their ultrastructure.", "content": "1. Effects of concanavalin A (Con A) and other lectins on 5-hydroxytryptamine (5-HT) uptake by rabbit blood platelets and on their ultrastructure were studied. 2. Uptake of [3H]-5-HT by platelets was decreased by application of Con A, E-PHA (lectin from Phaseolus vulgaris) and lentil-PHA (lectin from Lens culinaris), but not by wheat germ agglutinin (WGA). Con A induced specific changes in the ultrastructure of platelets, causing (i) a change in external appearance from a discoid to an irregularly spherical shape, (ii) re-arrangement of the canalicular system and formation of a concentric structure. These effects of Con A on platelets were antagonized by pretreatment with alpha-methyl-D-mannoside (alpha-MM), a specific inhibitor of Con A binding to glycoprotein. 3. The inhibition of 5-HT uptake by Con A was antagonized by colchicine, vinblastine and sodium nitroprusside (SNP), but not by cytochalasin B. 4. Theophylline, papaverine and dibutyryl cyclic adenosine 3',5'-monophosphate (db cyclic AMP) antagonized the effect of Con A on 5-HT uptake, but dibutyryl cyclic guanosine 3',5'-monophosphate had no effect. Theophylline and db cyclic AMP did not influence the effect of Con A on the ultrastructure of platelets. 5. It is suggested that binding of Con A to specific receptor glycoproteins can inhibit the 5-HT uptake system of platelets. Microtubules, contractile protein and the membrane adenylate cyclase system of platelets may also be regulatory factors in this mechanism.", "contents": "Effects of concanavalin A on 5-hydroxytryptamine uptake by rabbit blood platelets and on their ultrastructure. 1. Effects of concanavalin A (Con A) and other lectins on 5-hydroxytryptamine (5-HT) uptake by rabbit blood platelets and on their ultrastructure were studied. 2. Uptake of [3H]-5-HT by platelets was decreased by application of Con A, E-PHA (lectin from Phaseolus vulgaris) and lentil-PHA (lectin from Lens culinaris), but not by wheat germ agglutinin (WGA). Con A induced specific changes in the ultrastructure of platelets, causing (i) a change in external appearance from a discoid to an irregularly spherical shape, (ii) re-arrangement of the canalicular system and formation of a concentric structure. These effects of Con A on platelets were antagonized by pretreatment with alpha-methyl-D-mannoside (alpha-MM), a specific inhibitor of Con A binding to glycoprotein. 3. The inhibition of 5-HT uptake by Con A was antagonized by colchicine, vinblastine and sodium nitroprusside (SNP), but not by cytochalasin B. 4. Theophylline, papaverine and dibutyryl cyclic adenosine 3',5'-monophosphate (db cyclic AMP) antagonized the effect of Con A on 5-HT uptake, but dibutyryl cyclic guanosine 3',5'-monophosphate had no effect. Theophylline and db cyclic AMP did not influence the effect of Con A on the ultrastructure of platelets. 5. It is suggested that binding of Con A to specific receptor glycoproteins can inhibit the 5-HT uptake system of platelets. Microtubules, contractile protein and the membrane adenylate cyclase system of platelets may also be regulatory factors in this mechanism."}
{"id": "PMID:219927", "title": "The characteristics of [3H]-clonidine binding to an alpha-adrenoceptor in membranes from guinea-pig kidney.", "content": "1. [3H]-clonidine binds to membranes prepared from guinea-pig kidney. 2. At 25 degrees C the binding is rapid and saturable. 3. Scatchard analysis of the binding data showed that the Kd for [3H]-clonidine binding in kidney membranes is 8.54 nM and the density of binding sites 12.5 pmol/g wet wt. tissue. 4. Hill plots of the binding data showed that there were no cooperative site interactions associated with binding. 5. [3H]-clonidine binding could be displaced by drugs, the most potent being drugs with a high affinity for the alpha-adrenoceptor. The neuroleptic drugs (+)-butaclamol, cis-clopenthixol and cis-flupenthixol at high concentration also displaced [3H]-clonidine binding. 6. Drugs acting as agonists or antagonists of beta-adrenoceptors, histamine receptors, acetylcholine receptors as well as prostaglandins E1, E2, F1alpha and F2alpha, angiotensin II, arginine vasopressin, naloxone, nalorphine and pargyline had little effect on binding. 7. It is likely that the binding site labelled by [3H]-clonidine in guinea-pig kidney membranes is an alpha-adrenoceptor similar in some pharmacological aspects to an alpha2-adrenoceptor.", "contents": "The characteristics of [3H]-clonidine binding to an alpha-adrenoceptor in membranes from guinea-pig kidney. 1. [3H]-clonidine binds to membranes prepared from guinea-pig kidney. 2. At 25 degrees C the binding is rapid and saturable. 3. Scatchard analysis of the binding data showed that the Kd for [3H]-clonidine binding in kidney membranes is 8.54 nM and the density of binding sites 12.5 pmol/g wet wt. tissue. 4. Hill plots of the binding data showed that there were no cooperative site interactions associated with binding. 5. [3H]-clonidine binding could be displaced by drugs, the most potent being drugs with a high affinity for the alpha-adrenoceptor. The neuroleptic drugs (+)-butaclamol, cis-clopenthixol and cis-flupenthixol at high concentration also displaced [3H]-clonidine binding. 6. Drugs acting as agonists or antagonists of beta-adrenoceptors, histamine receptors, acetylcholine receptors as well as prostaglandins E1, E2, F1alpha and F2alpha, angiotensin II, arginine vasopressin, naloxone, nalorphine and pargyline had little effect on binding. 7. It is likely that the binding site labelled by [3H]-clonidine in guinea-pig kidney membranes is an alpha-adrenoceptor similar in some pharmacological aspects to an alpha2-adrenoceptor."}
{"id": "PMID:219928", "title": "The effects of opioid drugs and of lithium on steroidogenesis in rat adrenal cell suspensions.", "content": "1. The effects of opioid drugs and of Na+ replacement on steroidogenesis in rat adrenal cell suspensions were investigated. 2. In medium containing normal Na+ (156 mM), opioid antagonists but not opioid agonists reduced the steroidogenic response to adrenocorticotrophic hormone1-24 (ACTH1-24) but not to dibutyryl adenosine 3',5' cyclic monophosphate (db cyclic AMP). 3. Replacement of 50% Na+ in the medium by choline had no effect on steroidogenesis, but further reductions in Na+ content reduced the steroidogenic activity of both ACTH1-24 and db cyclic AMP. 4. In 50% Na+ medium both opioid agonists and antagonists inhibited ACTH1-24 induced steroidogenesis. 5. Addition of therapeutic concentrations of lithium to otherwise normal medium inhibited the steroidogenic response to ACTH1--24 but not to db cyclic AMP. 6. The selective inhibition of ACTH1--24-induced steroidogenesis by opioid drugs suggests some similarity between the opioid and ACTH receptors. 7. The relevance of the potent inhibitory effect of lithium to its therapeutic actions is discussed.", "contents": "The effects of opioid drugs and of lithium on steroidogenesis in rat adrenal cell suspensions. 1. The effects of opioid drugs and of Na+ replacement on steroidogenesis in rat adrenal cell suspensions were investigated. 2. In medium containing normal Na+ (156 mM), opioid antagonists but not opioid agonists reduced the steroidogenic response to adrenocorticotrophic hormone1-24 (ACTH1-24) but not to dibutyryl adenosine 3',5' cyclic monophosphate (db cyclic AMP). 3. Replacement of 50% Na+ in the medium by choline had no effect on steroidogenesis, but further reductions in Na+ content reduced the steroidogenic activity of both ACTH1-24 and db cyclic AMP. 4. In 50% Na+ medium both opioid agonists and antagonists inhibited ACTH1-24 induced steroidogenesis. 5. Addition of therapeutic concentrations of lithium to otherwise normal medium inhibited the steroidogenic response to ACTH1--24 but not to db cyclic AMP. 6. The selective inhibition of ACTH1--24-induced steroidogenesis by opioid drugs suggests some similarity between the opioid and ACTH receptors. 7. The relevance of the potent inhibitory effect of lithium to its therapeutic actions is discussed."}
{"id": "PMID:219931", "title": "Drug-induced peripheral neuropathies.", "content": "Review of the various drugs in current clinical use showed that over 50 of them may cause a purely sensory or mixed sensorimotor neuropathy. These include antimicrobials, such as isoniazid, ethambutol, ethionamide, nitrofurantoin, and metronidazole; antineoplastic agents, particularly vinca alkaloids; cardiovascular drugs, such as perhexiline and hydrallazine; hypnotics and psychotropics, notable methaqualone; antirheumatics, such as gold, indomethacin, and chloroquine; anticonvulsants, particularly phenytoin; and other drugs, including disulfiram, calcium carbimide, and dapsone. Patients receiving drug treatment who complain of paraesthesie, pain, muscle cramps, or other abnormal sensations and those without symptoms who are receiving drugs that are known or suspected to be neurotoxic should undergo neurological examination and studies of motor and sensory nerve conduction. This will allow the incidence of drug-induced peripheral neuropathy to be determined more precisely.", "contents": "Drug-induced peripheral neuropathies. Review of the various drugs in current clinical use showed that over 50 of them may cause a purely sensory or mixed sensorimotor neuropathy. These include antimicrobials, such as isoniazid, ethambutol, ethionamide, nitrofurantoin, and metronidazole; antineoplastic agents, particularly vinca alkaloids; cardiovascular drugs, such as perhexiline and hydrallazine; hypnotics and psychotropics, notable methaqualone; antirheumatics, such as gold, indomethacin, and chloroquine; anticonvulsants, particularly phenytoin; and other drugs, including disulfiram, calcium carbimide, and dapsone. Patients receiving drug treatment who complain of paraesthesie, pain, muscle cramps, or other abnormal sensations and those without symptoms who are receiving drugs that are known or suspected to be neurotoxic should undergo neurological examination and studies of motor and sensory nerve conduction. This will allow the incidence of drug-induced peripheral neuropathy to be determined more precisely."}
{"id": "PMID:219933", "title": "Immunity of children to diphtheria, tetanus, and poliomyelitis.", "content": "A survey of titres of diphtheria and tetanus antitoxins and of antibodies to polioviruses in the sera of 291 schoolchildren aged 15, 11, and 7 years showed that high immunisation rates can evoke protective concentrations of tetanus antitoxin in 98% of children and protective levels of the antibodies to diphtheria and all three types of poliomyelitis in 85% of children. Reinforcing immunisation at school entry appeared to be necessary to maintain adequate titres of diphtheria antitoxin in children up to 15 years of age, not essential to maintain adequate titres of tetanus antitoxin, and to have little effect on the titres of antibodies to poliomyelitis.", "contents": "Immunity of children to diphtheria, tetanus, and poliomyelitis. A survey of titres of diphtheria and tetanus antitoxins and of antibodies to polioviruses in the sera of 291 schoolchildren aged 15, 11, and 7 years showed that high immunisation rates can evoke protective concentrations of tetanus antitoxin in 98% of children and protective levels of the antibodies to diphtheria and all three types of poliomyelitis in 85% of children. Reinforcing immunisation at school entry appeared to be necessary to maintain adequate titres of diphtheria antitoxin in children up to 15 years of age, not essential to maintain adequate titres of tetanus antitoxin, and to have little effect on the titres of antibodies to poliomyelitis."}
{"id": "PMID:219935", "title": "High-density lipoprotein in chronic renal failure and after renal transplantation.", "content": "Serum high-density-lipoprotein (HDL) cholesterol and apoprotein (apo) A concentrations were significantly reduced at the time of renal transplantation in 26 patients with chronic renal failure. In a prospective evaluation the behaviour of HDL concentrations after grafting was found to depend on renal function. Graft function was sustained in 19 patients, in whom HDL-cholesterol and apo A concentrations increased to lie within normal limits by six months after the operation. Successful transplantation also restored to normal the lipid and protein content of HDL as expressed by the ratio of HDL cholesterol to apo A. When transplant function was not sustained (seven patients), however, no changes in HDL were observed up to the time of the graft loss. Such changes in HDL with successful kidney grafting augur well in a population with many risk factors for coronary heart disease.", "contents": "High-density lipoprotein in chronic renal failure and after renal transplantation. Serum high-density-lipoprotein (HDL) cholesterol and apoprotein (apo) A concentrations were significantly reduced at the time of renal transplantation in 26 patients with chronic renal failure. In a prospective evaluation the behaviour of HDL concentrations after grafting was found to depend on renal function. Graft function was sustained in 19 patients, in whom HDL-cholesterol and apo A concentrations increased to lie within normal limits by six months after the operation. Successful transplantation also restored to normal the lipid and protein content of HDL as expressed by the ratio of HDL cholesterol to apo A. When transplant function was not sustained (seven patients), however, no changes in HDL were observed up to the time of the graft loss. Such changes in HDL with successful kidney grafting augur well in a population with many risk factors for coronary heart disease."}
{"id": "PMID:219937", "title": "Relation between plasma hormone profiles, symptoms, and response to oestrogen treatment in women approaching the menopause.", "content": "Out of a consecutive series of 300 patients seen at a menopause clinic, 82 complained of symptoms generally associated with the climacteric, although they were still menstruating. Vasomotor disturbances were absent in 42 of these patients (group 1) and present in 40 (group 2). Headaches, insomnia, and dyspareunia were the most common complaints among the women with vasomotor symptoms, whereas loss of libido and depression predominated in those without. Conjugated equine oestrogens (Premarin) 1.25 mg daily given for three weeks out of four relieved nearly all symptoms in group 2, but in group 1 the response was disappointing. The mean plasma oestradiol concentration in women with vasomotor symptoms was significantly lower than that observed during days 1-10 of the menstrual cycle, but plasma testosterone values were not significantly different from those observed in younger women. Plasma follicle-stimulating hormone (FSH) and luteinising hormone  (LH) concentrations were similar to those seen after the menopause. Concentrations of these hormones in the women without vasomotor symptoms were similar to those in the younger, regularly menstruating women. After six months of oestrogen treatment patients in group 2 had a 2.1-fold increase in mean plasma oestradiol concentration, and plasma FSH and LH concentrations were reduced to 39% and 66% of their pretreatment values respectively; in group 1, however, no such pronounced changes occurred. High concentrations of FSH were present in patients with oestrogen-responsive symptoms, 15 U/1 being the diagnostic cut-off point. This measurement in the presence of characteristic symptoms therefore constitutes the best method of selecting patients for oestrogen-replacement therapy.", "contents": "Relation between plasma hormone profiles, symptoms, and response to oestrogen treatment in women approaching the menopause. Out of a consecutive series of 300 patients seen at a menopause clinic, 82 complained of symptoms generally associated with the climacteric, although they were still menstruating. Vasomotor disturbances were absent in 42 of these patients (group 1) and present in 40 (group 2). Headaches, insomnia, and dyspareunia were the most common complaints among the women with vasomotor symptoms, whereas loss of libido and depression predominated in those without. Conjugated equine oestrogens (Premarin) 1.25 mg daily given for three weeks out of four relieved nearly all symptoms in group 2, but in group 1 the response was disappointing. The mean plasma oestradiol concentration in women with vasomotor symptoms was significantly lower than that observed during days 1-10 of the menstrual cycle, but plasma testosterone values were not significantly different from those observed in younger women. Plasma follicle-stimulating hormone (FSH) and luteinising hormone  (LH) concentrations were similar to those seen after the menopause. Concentrations of these hormones in the women without vasomotor symptoms were similar to those in the younger, regularly menstruating women. After six months of oestrogen treatment patients in group 2 had a 2.1-fold increase in mean plasma oestradiol concentration, and plasma FSH and LH concentrations were reduced to 39% and 66% of their pretreatment values respectively; in group 1, however, no such pronounced changes occurred. High concentrations of FSH were present in patients with oestrogen-responsive symptoms, 15 U/1 being the diagnostic cut-off point. This measurement in the presence of characteristic symptoms therefore constitutes the best method of selecting patients for oestrogen-replacement therapy."}
{"id": "PMID:219938", "title": "Neutral and acid sphingomyelinases: somatotopographical distribution in human brain and distribution in rat organs. A possible relationship with the dopamine system.", "content": "Acid and neutral sphingomyelinase activities have been measured in 22 regions of human brain, and in several rat organs. In general, acid sphingomyelinase activity was similar in most brain regions examined. By contrast neutral sphingomyelinase activity decreased 30-fold between the globus pallidus and white matter. In grey matter structures activity decreased in the order globus pallidus greater than substantia nigra greater than or equal to putamen greater than head of caudate greater than thalamus greater than cortical structures. Under the conditions of assay and in the presence of several possible donors or acceptors, there was no evidence of transfer of phosphoryl-choline to other lipid acceptors. Acid sphingomyelinase was ubiquitously distributed in all rat tissues examined, highest in liver and lowest in adipose tissue. Neutral sphingomyelinase activity was highest in brain; activity from 25 to 10% of that in brain was observed in testis, adrenal gland and aorta. Activity in the other organs examined was less than 10% of that in brain. We suggest that the neutral enzyme serves a special function in brain, perhaps related to the dopaminergic systems.", "contents": "Neutral and acid sphingomyelinases: somatotopographical distribution in human brain and distribution in rat organs. A possible relationship with the dopamine system. Acid and neutral sphingomyelinase activities have been measured in 22 regions of human brain, and in several rat organs. In general, acid sphingomyelinase activity was similar in most brain regions examined. By contrast neutral sphingomyelinase activity decreased 30-fold between the globus pallidus and white matter. In grey matter structures activity decreased in the order globus pallidus greater than substantia nigra greater than or equal to putamen greater than head of caudate greater than thalamus greater than cortical structures. Under the conditions of assay and in the presence of several possible donors or acceptors, there was no evidence of transfer of phosphoryl-choline to other lipid acceptors. Acid sphingomyelinase was ubiquitously distributed in all rat tissues examined, highest in liver and lowest in adipose tissue. Neutral sphingomyelinase activity was highest in brain; activity from 25 to 10% of that in brain was observed in testis, adrenal gland and aorta. Activity in the other organs examined was less than 10% of that in brain. We suggest that the neutral enzyme serves a special function in brain, perhaps related to the dopaminergic systems."}
{"id": "PMID:219939", "title": "ACTH-like neurotropic peptides: possible regulators of rat brain cyclic AMP.", "content": "The influence of behaviorally active, N-terminal fragments of ACTH on the accumulation of cAMP in rat brain investigated in broken cell preparations of subcortical tissue, in slices of neostriatum and in vivo. ACTH1--24 has a biphasic effect on the activity of adenylate cyclase in broken cell preparations of rat brain subcortical tissue: concentrations below 25 micrometer stimulated, whereas concentrations of 0.1 mM and higher inhibited adenylate cyclase activity. The magnitude of the stimulation was dependent on the concentrations of ATP and Mg2+ in the incubation medium. Structure activity studies revealed that at a concentration of 10(-4) M ACTH1--16-NH2 and ACTH4--7 also inhibited the activity of adenylate cyclase, whereas ACTH11--24, ACTH1--10, ACTH4--10, [D-Phe7]ACTH1--10 and [D-Phe7]ACTH4--10 were inactive in this respect. Addition of 0.8 mM EGTA but not of 0.25 mM Ca2+ prevented the inhibition by 10(-4) M ACTH1--24. GMP-N-P (10(-5) M), naltrexone (10(-3) M) and ergometrine (10(-3) M) did not influence the inhibitory effect. ACTH1--24 enhanced the accumulation of cAMP in slices from rat brain neostriatum in a dose-dependent manner. This effect was already maximal 7.5 min after the addition of the peptide and was potentiated by isobutylmethylxanthine, a potent inhibitor or phosphodiesterase. Intraventricular injection of 1 microgram ACTH1--16-NH2 in rats significantly elevated (+ 27%) the concentration of cAMP in the septal region 60 min after the injection of the peptide. The results are discussed in terms of a possible involvement of cAMP as a second messenger in the central nervous system for N-terminal fragments of ACTH.", "contents": "ACTH-like neurotropic peptides: possible regulators of rat brain cyclic AMP. The influence of behaviorally active, N-terminal fragments of ACTH on the accumulation of cAMP in rat brain investigated in broken cell preparations of subcortical tissue, in slices of neostriatum and in vivo. ACTH1--24 has a biphasic effect on the activity of adenylate cyclase in broken cell preparations of rat brain subcortical tissue: concentrations below 25 micrometer stimulated, whereas concentrations of 0.1 mM and higher inhibited adenylate cyclase activity. The magnitude of the stimulation was dependent on the concentrations of ATP and Mg2+ in the incubation medium. Structure activity studies revealed that at a concentration of 10(-4) M ACTH1--16-NH2 and ACTH4--7 also inhibited the activity of adenylate cyclase, whereas ACTH11--24, ACTH1--10, ACTH4--10, [D-Phe7]ACTH1--10 and [D-Phe7]ACTH4--10 were inactive in this respect. Addition of 0.8 mM EGTA but not of 0.25 mM Ca2+ prevented the inhibition by 10(-4) M ACTH1--24. GMP-N-P (10(-5) M), naltrexone (10(-3) M) and ergometrine (10(-3) M) did not influence the inhibitory effect. ACTH1--24 enhanced the accumulation of cAMP in slices from rat brain neostriatum in a dose-dependent manner. This effect was already maximal 7.5 min after the addition of the peptide and was potentiated by isobutylmethylxanthine, a potent inhibitor or phosphodiesterase. Intraventricular injection of 1 microgram ACTH1--16-NH2 in rats significantly elevated (+ 27%) the concentration of cAMP in the septal region 60 min after the injection of the peptide. The results are discussed in terms of a possible involvement of cAMP as a second messenger in the central nervous system for N-terminal fragments of ACTH."}
{"id": "PMID:219946", "title": "Mineral substance of bone tissue and of experimental cutaneous calcinosis in rats: chemical analysis and ESR study.", "content": "The evolution of the mineral constituents of subcutaneous calcinosis induced in rats by topical calciphylaxis was studied by the method of quantitative chemical analysis, and after treatment with excited gases by electron spin resonance (ESR) analysis. Chemical data show that the genesis of the subcutaneous calcinosis does not significantly alter the concentration of Ca, P, F, CO3, Mg, and Fe in the mineral phase of the femoral bone of calciphylactic rats. In the calcinosis an important increase of the fluoride concentration is noticed in function of the time after challenging. There is also a high concentration of Mg2+ ions in the early stages of the experimental calcification. Iron injected for the challenging is continuously present in the calciphylactic tissue after this treatment. This suggests that subcutaneous calcinosis might be a means of fixing certain heavy metal ions. After treatment with excited gases, the proportions of the trapped CO33- and O3- radicals are of the same order of magnitude in calciphylactic tissue after 12 days and observations in bone mineral. These suggest that after 12 days the mineral of the calciphylactic tissue has a crystalline state close to that of bone.", "contents": "Mineral substance of bone tissue and of experimental cutaneous calcinosis in rats: chemical analysis and ESR study. The evolution of the mineral constituents of subcutaneous calcinosis induced in rats by topical calciphylaxis was studied by the method of quantitative chemical analysis, and after treatment with excited gases by electron spin resonance (ESR) analysis. Chemical data show that the genesis of the subcutaneous calcinosis does not significantly alter the concentration of Ca, P, F, CO3, Mg, and Fe in the mineral phase of the femoral bone of calciphylactic rats. In the calcinosis an important increase of the fluoride concentration is noticed in function of the time after challenging. There is also a high concentration of Mg2+ ions in the early stages of the experimental calcification. Iron injected for the challenging is continuously present in the calciphylactic tissue after this treatment. This suggests that subcutaneous calcinosis might be a means of fixing certain heavy metal ions. After treatment with excited gases, the proportions of the trapped CO33- and O3- radicals are of the same order of magnitude in calciphylactic tissue after 12 days and observations in bone mineral. These suggest that after 12 days the mineral of the calciphylactic tissue has a crystalline state close to that of bone."}
{"id": "PMID:219947", "title": "Acetylcholinesterase: characterization of native and proteolytically derived forms and identification of structural protein components.", "content": "The assymmetric 18S and 14S forms of acetylcholinesterase (EC 3.1.1.7) from Electrophorus electricus purified by affinity chromatography on N-methylacridinium Sepharose 2B were subjected to trypsin or collagenase proteolysis and changes in the enzyme composition and structure were monitored by sucrose gradient sedimentation, gel chromatography, and sodium dodecyl sulphate - polyacrylamide gel electrophoresis. A distinction between autolytic and tryptic degradation products is described and the generation of two new forms of acetylcholinesterase from the 18S and 14S enzyme by collagenase proteolysis is reported. The species derived from the 18S form of acetylcholinesterase has a sedimentation coefficient of 21.1S and a Stokes radius of 12.9 nm while the 14S form gives rise to a 17.3S species with a Stokes radius of 11.1 nm. The proteolytically sensitive component ('tail') of the asymmetric forms of acetylcholinesterase is identified with a subunit of 45 000 daltons on sodium dodecyl sulphate - polyacrylamide electrophoresis gels.", "contents": "Acetylcholinesterase: characterization of native and proteolytically derived forms and identification of structural protein components. The assymmetric 18S and 14S forms of acetylcholinesterase (EC 3.1.1.7) from Electrophorus electricus purified by affinity chromatography on N-methylacridinium Sepharose 2B were subjected to trypsin or collagenase proteolysis and changes in the enzyme composition and structure were monitored by sucrose gradient sedimentation, gel chromatography, and sodium dodecyl sulphate - polyacrylamide gel electrophoresis. A distinction between autolytic and tryptic degradation products is described and the generation of two new forms of acetylcholinesterase from the 18S and 14S enzyme by collagenase proteolysis is reported. The species derived from the 18S form of acetylcholinesterase has a sedimentation coefficient of 21.1S and a Stokes radius of 12.9 nm while the 14S form gives rise to a 17.3S species with a Stokes radius of 11.1 nm. The proteolytically sensitive component ('tail') of the asymmetric forms of acetylcholinesterase is identified with a subunit of 45 000 daltons on sodium dodecyl sulphate - polyacrylamide electrophoresis gels."}
{"id": "PMID:219948", "title": "Protein kinase activity and ribosome phosphorylation in ethionine-treated rats.", "content": "The regulation of protein synthesis at the level of the ribosome was investigated using the model system of ethionine-induced inhibition of protein synthesis. The phosphorylation of ribosomal protein S6 was examined in vivo during ethionine intoxication and during the adenine-induced reversal of ethionine intoxication. The extent of phosphorylation of S6 correlated well with protein synthetic activity observed after ethionine, and ethionine followed by adenine treatments. No clear correlation was observed in the ethionine system between cyclic adenosine 3':5'-monophosphate concentration or the activity of ribosomal protein kinase and the phosphorylation of ribosomal protein S6. A role for a cyclic adenosine 3':5'-monophosphate-dependent ribosomal phosphoprotein phosphatase is postulated.", "contents": "Protein kinase activity and ribosome phosphorylation in ethionine-treated rats. The regulation of protein synthesis at the level of the ribosome was investigated using the model system of ethionine-induced inhibition of protein synthesis. The phosphorylation of ribosomal protein S6 was examined in vivo during ethionine intoxication and during the adenine-induced reversal of ethionine intoxication. The extent of phosphorylation of S6 correlated well with protein synthetic activity observed after ethionine, and ethionine followed by adenine treatments. No clear correlation was observed in the ethionine system between cyclic adenosine 3':5'-monophosphate concentration or the activity of ribosomal protein kinase and the phosphorylation of ribosomal protein S6. A role for a cyclic adenosine 3':5'-monophosphate-dependent ribosomal phosphoprotein phosphatase is postulated."}
{"id": "PMID:219949", "title": "Thermally induced changes in reconstituted and membranous cytochrome c oxidase.", "content": "The Arrhenius plots of electron transport activity in cytochrome c oxidase reconstituted with well-defined phospholipids have been shown to display a change in slope at 20--25 degrees C regardless of the chemical nature of the incorporated lipid. In native membranous cytochrome c oxidase, the discontinuity in Arrhenius activity plot occurred at 16--18 degrees C. These temperature breaks were found to correlate with changes in spin-label mobilities but not with the bulk lipid transition observed by differential scanning calorimetry. Temperature-dependent reciprocal equilibrium between the immobilized and fluid pools is demonstrated. It is suggested that the changes in kinetic and spin-label spectral characteristics in cytochrome c oxidase membranes are related very likely to a lipid-protein interaction prompted by a thermally induced change in the physical state of the lipids that does not involve a gel to liquid crystalline transition.", "contents": "Thermally induced changes in reconstituted and membranous cytochrome c oxidase. The Arrhenius plots of electron transport activity in cytochrome c oxidase reconstituted with well-defined phospholipids have been shown to display a change in slope at 20--25 degrees C regardless of the chemical nature of the incorporated lipid. In native membranous cytochrome c oxidase, the discontinuity in Arrhenius activity plot occurred at 16--18 degrees C. These temperature breaks were found to correlate with changes in spin-label mobilities but not with the bulk lipid transition observed by differential scanning calorimetry. Temperature-dependent reciprocal equilibrium between the immobilized and fluid pools is demonstrated. It is suggested that the changes in kinetic and spin-label spectral characteristics in cytochrome c oxidase membranes are related very likely to a lipid-protein interaction prompted by a thermally induced change in the physical state of the lipids that does not involve a gel to liquid crystalline transition."}
{"id": "PMID:219950", "title": "Polymyxin resistance in Agrobacterium tumefaciens and its effect on crown gall tumor induction.", "content": "Polymyxin-resistant (PBLr) mutants of Agrobacterium tumefaciens A6, B6, and B6M were isolated from polymyxin-sensitive (PBLs) parent strains in a defined medium containing 600 microgram of polymyxin B sulfate per millilitre. The weight and number of tumors induced by PBLr mutants on a variety of host plants such as carrot, potato, and pinto bean were 45--75% less than those induced by PBLs wild types. The crude cell envelopes (CCE) prepared from both PBLs and PBLr bacteria were inhibitory for tumor initiation when they were applied before or during the inoculation of viable tumorigenic bacteria, but not when they were applied 30 min after the inoculation of infectious bacteria. The potency to inhibit the tumor initiation by the CCE prepared from PBLs cells was approximately 50% higher than that by the equal amount of the CCE prepared from PBLr cells. The concentration of CCE preparations required to reduce tumor induction 50% in carrot and pinto bean was determined to be 2.6 mg/mL and 4.0--6.2 mg/mL for the CCE derived from PBLs and PBLr cells, respectively. These data suggest that the envelope structure or composition of PBLs and PBLr cells is distinct, and that the acquisition of resistance to polymyxin by agrobacteria modifies envelope structure or components which are essential for tumor initiation.", "contents": "Polymyxin resistance in Agrobacterium tumefaciens and its effect on crown gall tumor induction. Polymyxin-resistant (PBLr) mutants of Agrobacterium tumefaciens A6, B6, and B6M were isolated from polymyxin-sensitive (PBLs) parent strains in a defined medium containing 600 microgram of polymyxin B sulfate per millilitre. The weight and number of tumors induced by PBLr mutants on a variety of host plants such as carrot, potato, and pinto bean were 45--75% less than those induced by PBLs wild types. The crude cell envelopes (CCE) prepared from both PBLs and PBLr bacteria were inhibitory for tumor initiation when they were applied before or during the inoculation of viable tumorigenic bacteria, but not when they were applied 30 min after the inoculation of infectious bacteria. The potency to inhibit the tumor initiation by the CCE prepared from PBLs cells was approximately 50% higher than that by the equal amount of the CCE prepared from PBLr cells. The concentration of CCE preparations required to reduce tumor induction 50% in carrot and pinto bean was determined to be 2.6 mg/mL and 4.0--6.2 mg/mL for the CCE derived from PBLs and PBLr cells, respectively. These data suggest that the envelope structure or composition of PBLs and PBLr cells is distinct, and that the acquisition of resistance to polymyxin by agrobacteria modifies envelope structure or components which are essential for tumor initiation."}
{"id": "PMID:219951", "title": "Cyclic adenosine 3', 5'-monophosphate in Neisseria gonorrhoeae.", "content": "Intracellular cyclic adenosine 3', 5'-monophosphate (cAMP) was measured in two laboratory strains of Neisseria gonorrhoeae. Decreasing the glucose content of a defined media from 33 mM to 5.5 mM glucose resulted in an 11-to 25-fold increase of intracellular cAMP.", "contents": "Cyclic adenosine 3', 5'-monophosphate in Neisseria gonorrhoeae. Intracellular cyclic adenosine 3', 5'-monophosphate (cAMP) was measured in two laboratory strains of Neisseria gonorrhoeae. Decreasing the glucose content of a defined media from 33 mM to 5.5 mM glucose resulted in an 11-to 25-fold increase of intracellular cAMP."}
{"id": "PMID:219952", "title": "Infectious bursal agent vaccination of chicks from infectious bursal agent-vaccinated dams.", "content": "Chicks from infectious bursal agent-vaccinated broiler breeders were vaccinated with a commercial infectious bursal agent vaccine at intervals after hatching. Bursas from some of these chicks were examined for infectious bursal agent-specific fluorescence four days after vaccination and bursas from others were examined for histological lesions of infectious bursal disease 21 days after vaccination. Serological studies were conducted to determine if active immunity to infectious bursal agent followed vaccination. Chicks failed to develop immunity if their levels of maternally-derived serum neutralizing antibody were in excess of approximately log(2) 7 at the time of vaccination. When antibody titres fell below this level, vaccination usually resulted in infectious bursal agent virus replication in the bursa and consequential bursal damage but was followed by development of active immunity.", "contents": "Infectious bursal agent vaccination of chicks from infectious bursal agent-vaccinated dams. Chicks from infectious bursal agent-vaccinated broiler breeders were vaccinated with a commercial infectious bursal agent vaccine at intervals after hatching. Bursas from some of these chicks were examined for infectious bursal agent-specific fluorescence four days after vaccination and bursas from others were examined for histological lesions of infectious bursal disease 21 days after vaccination. Serological studies were conducted to determine if active immunity to infectious bursal agent followed vaccination. Chicks failed to develop immunity if their levels of maternally-derived serum neutralizing antibody were in excess of approximately log(2) 7 at the time of vaccination. When antibody titres fell below this level, vaccination usually resulted in infectious bursal agent virus replication in the bursa and consequential bursal damage but was followed by development of active immunity."}
{"id": "PMID:219953", "title": "Tumor promoter 12-O-tetradecanoylphorbol-13-acetate is not a prostaglandin E-type agonist.", "content": "The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), proposed to fit a prostaglandin type receptor, does not compete with [3H] prostaglandin E1 (PGE1) for the established PGE1 receptor of fat cells.", "contents": "Tumor promoter 12-O-tetradecanoylphorbol-13-acetate is not a prostaglandin E-type agonist. The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), proposed to fit a prostaglandin type receptor, does not compete with [3H] prostaglandin E1 (PGE1) for the established PGE1 receptor of fat cells."}
{"id": "PMID:219954", "title": "Simultaneous production of casein and mammary tumor virus in mouse mammary epithelial cells grown on floating collagen gels.", "content": "Simultaneous production of casein and mammary tumor virus (MTV) was analyzed in monolayer cultures of mammary epithelial cells from pregnant BALB/cfC3H mice. A comparison of the 2 cell culture substrata, plastic culture dish and floating collagen gel, showed that the latter supported a much higher degree of simultaneous casein and MTV production in the presence of insulin, cortisol and prolactin in serum-free culture medium. Importance of floating collagen gel was further shown by delaying the flotation of gels. When the release of gels was delayed, there were concomitant delays in the increase of casein and MTV production. These results indicate that hormones, nature of substratum and flotation regulate the degree of differentiation of mammary epithelial cells in vitro.", "contents": "Simultaneous production of casein and mammary tumor virus in mouse mammary epithelial cells grown on floating collagen gels. Simultaneous production of casein and mammary tumor virus (MTV) was analyzed in monolayer cultures of mammary epithelial cells from pregnant BALB/cfC3H mice. A comparison of the 2 cell culture substrata, plastic culture dish and floating collagen gel, showed that the latter supported a much higher degree of simultaneous casein and MTV production in the presence of insulin, cortisol and prolactin in serum-free culture medium. Importance of floating collagen gel was further shown by delaying the flotation of gels. When the release of gels was delayed, there were concomitant delays in the increase of casein and MTV production. These results indicate that hormones, nature of substratum and flotation regulate the degree of differentiation of mammary epithelial cells in vitro."}
{"id": "PMID:219955", "title": "Initiation-promotion skin carcinogenesis: inhibition by cyclic and non-cyclic nucleotides.", "content": "The effect of nucleotides on initiation-promotion skin carcinogenesis in Swiss mice was investigated. Cyclic AMP was given before initiation with DMBA, between initiation and promotion, and at the same time as promotion with croton oil. Cyclic AMP was more effective in inhibiting tumor development when injected at the same as promotion with croton oil. 5'-adenosine-monophosphate (5'-AMP) and cyclic GMP were as effective as cyclic AMP in inhibiting tumor development under these conditions. However, adenosine, dibutyryl-cyclic AMP and 5'-guanosine-monophosphate (5'-GMP) were ineffective.", "contents": "Initiation-promotion skin carcinogenesis: inhibition by cyclic and non-cyclic nucleotides. The effect of nucleotides on initiation-promotion skin carcinogenesis in Swiss mice was investigated. Cyclic AMP was given before initiation with DMBA, between initiation and promotion, and at the same time as promotion with croton oil. Cyclic AMP was more effective in inhibiting tumor development when injected at the same as promotion with croton oil. 5'-adenosine-monophosphate (5'-AMP) and cyclic GMP were as effective as cyclic AMP in inhibiting tumor development under these conditions. However, adenosine, dibutyryl-cyclic AMP and 5'-guanosine-monophosphate (5'-GMP) were ineffective."}
{"id": "PMID:219956", "title": "Dissociation between cardiac cyclic AMP and myocardial contractility induced by verapamil, calcium and magnesium ions.", "content": "Isolated, perfused rat hearts were used to study the effects of verapamil, excess calcium ions or excess magnesium ions on changes in heart cyclic AMP and myocardial force of contraction. Verapamil caused a dose-dependent decrease in force of contraction and a nondose-related reduction in cyclic AMP. Perfusion of hearts with medium containing 5 mM calcium produced a significant rise in cyclic AMP, but no change in contractile force. The depressant effects of verapamil on contractility and cyclic AMP were reversed by 5mM calcium; excess calcium in the perfusion fluid also containing verapamil prevented the myocardial depressant effects of verapamil. Acutely elevating the magnesium concentration in the perfusion medium decreased force of contraction, accentuated the negative inotropic effect of verapamil, but did not decrease cyclic AMP or enhance the verapamil-induced reduction in cyclic AMP.", "contents": "Dissociation between cardiac cyclic AMP and myocardial contractility induced by verapamil, calcium and magnesium ions. Isolated, perfused rat hearts were used to study the effects of verapamil, excess calcium ions or excess magnesium ions on changes in heart cyclic AMP and myocardial force of contraction. Verapamil caused a dose-dependent decrease in force of contraction and a nondose-related reduction in cyclic AMP. Perfusion of hearts with medium containing 5 mM calcium produced a significant rise in cyclic AMP, but no change in contractile force. The depressant effects of verapamil on contractility and cyclic AMP were reversed by 5mM calcium; excess calcium in the perfusion fluid also containing verapamil prevented the myocardial depressant effects of verapamil. Acutely elevating the magnesium concentration in the perfusion medium decreased force of contraction, accentuated the negative inotropic effect of verapamil, but did not decrease cyclic AMP or enhance the verapamil-induced reduction in cyclic AMP."}
{"id": "PMID:219960", "title": "[Oncological cytodiagnosis of the mammary gland].", "content": "Oncological mammary cytodiagnosis concerns a secretion, imprint, and punction. It is an integral and unsubstitutable part of the team cooperation in the counselling and prophylactic medical activity. Its pros are made use of in the field of prebioptic selection. Together with clinical and X-ray examination it forms a diagnostic whole which can be used in active prophylaxis as a method of screening. The arbiter of suspect and positive findings is biopsy.", "contents": "[Oncological cytodiagnosis of the mammary gland]. Oncological mammary cytodiagnosis concerns a secretion, imprint, and punction. It is an integral and unsubstitutable part of the team cooperation in the counselling and prophylactic medical activity. Its pros are made use of in the field of prebioptic selection. Together with clinical and X-ray examination it forms a diagnostic whole which can be used in active prophylaxis as a method of screening. The arbiter of suspect and positive findings is biopsy."}
{"id": "PMID:219963", "title": "The role of antitumor antibiotics in current oncologic practice.", "content": "The antitumor antibiotics have thus made a major impact on oncologic practice. The continued search for productive strains of these organisms should be encouraged; in addition, the activity and toxicity spectrum suggests the need for vigorous analogue development. An active anthracycline devoid of cardiotoxicity, a bleomycin with no effect on pulmonary tissue, an analogue of streptozoticin devoid of nephrotoxicity -- these would be advances of inestimable benefit to the cancer patient of the future.", "contents": "The role of antitumor antibiotics in current oncologic practice. The antitumor antibiotics have thus made a major impact on oncologic practice. The continued search for productive strains of these organisms should be encouraged; in addition, the activity and toxicity spectrum suggests the need for vigorous analogue development. An active anthracycline devoid of cardiotoxicity, a bleomycin with no effect on pulmonary tissue, an analogue of streptozoticin devoid of nephrotoxicity -- these would be advances of inestimable benefit to the cancer patient of the future."}
{"id": "PMID:219965", "title": "Glycosylated hemoglobin assay and oral glucose tolerance test compared for detection of diabetes mellitus.", "content": "We compared the oral glucose tolerance test (I) as evaluated by six commonly used scoring methods and total glycohemoglobin assay (II) with respect to their value in the diagnosis of diabetes mellitus. Depending on the evaluation method used for I, 16.7 to 64.3% of those subjects diagnosed as diabetic or borderline by this test were judged to be normal by II. The best agreement was between II and the Unger evaluation method. High-density-lipoprotein cholesterol, which showed an inverse correlation with II, was decreased in subjects judged to be diabetic by the Unger method. We conclude that the utilization of II measurement as a screening method for diabetes mellitus is consistent with a conservative approach to the diagnosis of diabetes.", "contents": "Glycosylated hemoglobin assay and oral glucose tolerance test compared for detection of diabetes mellitus. We compared the oral glucose tolerance test (I) as evaluated by six commonly used scoring methods and total glycohemoglobin assay (II) with respect to their value in the diagnosis of diabetes mellitus. Depending on the evaluation method used for I, 16.7 to 64.3% of those subjects diagnosed as diabetic or borderline by this test were judged to be normal by II. The best agreement was between II and the Unger evaluation method. High-density-lipoprotein cholesterol, which showed an inverse correlation with II, was decreased in subjects judged to be diabetic by the Unger method. We conclude that the utilization of II measurement as a screening method for diabetes mellitus is consistent with a conservative approach to the diagnosis of diabetes."}
{"id": "PMID:219966", "title": "Simplified immunonephelometric quantitation of apolipoprotein B in hyperlipoproteinemic serum.", "content": "An immunonephelometric procedure for determination of apolipoprotein B in human serum [Clin. Chem, 25, 221-226 (1979)] was modified by using the detergent octadecenylamine-polyoxyethylene, which may bind selectively to the phospholipid moiety of lipoproteins. Preincubation of hyperlipemic serum samples with lipases could then be omitted.", "contents": "Simplified immunonephelometric quantitation of apolipoprotein B in hyperlipoproteinemic serum. An immunonephelometric procedure for determination of apolipoprotein B in human serum [Clin. Chem, 25, 221-226 (1979)] was modified by using the detergent octadecenylamine-polyoxyethylene, which may bind selectively to the phospholipid moiety of lipoproteins. Preincubation of hyperlipemic serum samples with lipases could then be omitted."}
{"id": "PMID:219969", "title": "Simple and rapid method for the diagnosis of chronic granulomatous disease, measuring hydrogen peroxide and superoxide anions released from leukocytes in whole blood.", "content": "A simple quantitative method to measure release of hydrogen peroxide and superoxide anions from leukocytes using less than 10 microliter blood is described. Whole blood instead of a leukocyte suspension was used. The release of hydrogen peroxide was measured fluorometrically by adding a blood sample to an assay mixture containing homovanillic acid, peroxidase and azide. The release of superoxide anions was measured spectrophotometrically with a dual wavelength spectrophotometer by adding a blood sample to an assay mixture containing cytochrome C. The normal values of the releasing activities are given.", "contents": "Simple and rapid method for the diagnosis of chronic granulomatous disease, measuring hydrogen peroxide and superoxide anions released from leukocytes in whole blood. A simple quantitative method to measure release of hydrogen peroxide and superoxide anions from leukocytes using less than 10 microliter blood is described. Whole blood instead of a leukocyte suspension was used. The release of hydrogen peroxide was measured fluorometrically by adding a blood sample to an assay mixture containing homovanillic acid, peroxidase and azide. The release of superoxide anions was measured spectrophotometrically with a dual wavelength spectrophotometer by adding a blood sample to an assay mixture containing cytochrome C. The normal values of the releasing activities are given."}
{"id": "PMID:219970", "title": "Serum angiotensin converting enzyme activity in patients with chronic renal failure on long term hemodialysis.", "content": "Serum angiotensin converting enzyme activity was assayed by a spectrofluorometric method in 19 patients with chronic renal failure on long term hemodialysis and 19 control subjects. Converting enzyme activity was increased in 11 of 19 (58%) patients compared with the controls (p less than 0.005). There was no correlation between serum converting enzyme activity and plasma renin activity or blood pressure in the patients. Possible mechanisms responsible for the increased converting enzyme activity are discussed.", "contents": "Serum angiotensin converting enzyme activity in patients with chronic renal failure on long term hemodialysis. Serum angiotensin converting enzyme activity was assayed by a spectrofluorometric method in 19 patients with chronic renal failure on long term hemodialysis and 19 control subjects. Converting enzyme activity was increased in 11 of 19 (58%) patients compared with the controls (p less than 0.005). There was no correlation between serum converting enzyme activity and plasma renin activity or blood pressure in the patients. Possible mechanisms responsible for the increased converting enzyme activity are discussed."}
{"id": "PMID:219971", "title": "Lipoprotein spectrum analysis of uremic patients maintained on chronic hemodialysis.", "content": "It is known that patients maintained on chronic hemodialysis have elevated plasma lipids. In order to establish whether the type of kidney pathology is related to a specific lipoprotein abnormality, we measured plasma lipoprotein in eight patients with glomerulonephritis, two patients with polycystic kidney disease and nine patients that had been surgically nephrectomized. The concentration and composition of plasma very low density lipoproteins (VLDL), low density lipoproteins (LDL) and high density lipoproteins (HDL) in patients were compared to plasma lipoproteins in a control group. In all patient groups, the lipoprotein alterations appeared identical. VLDL were elevated 3 to 4 fold, LDL were decreased 15--35% and HDL were decreased 30--45% when compared to values of our control group. Since no differences in the lipoprotein spectrum were found among the patient groups, it appears that the hypertriglyceridemia of chronic uremia is due to the uremic state per se and is not related to a specific pathology of the kidney.", "contents": "Lipoprotein spectrum analysis of uremic patients maintained on chronic hemodialysis. It is known that patients maintained on chronic hemodialysis have elevated plasma lipids. In order to establish whether the type of kidney pathology is related to a specific lipoprotein abnormality, we measured plasma lipoprotein in eight patients with glomerulonephritis, two patients with polycystic kidney disease and nine patients that had been surgically nephrectomized. The concentration and composition of plasma very low density lipoproteins (VLDL), low density lipoproteins (LDL) and high density lipoproteins (HDL) in patients were compared to plasma lipoproteins in a control group. In all patient groups, the lipoprotein alterations appeared identical. VLDL were elevated 3 to 4 fold, LDL were decreased 15--35% and HDL were decreased 30--45% when compared to values of our control group. Since no differences in the lipoprotein spectrum were found among the patient groups, it appears that the hypertriglyceridemia of chronic uremia is due to the uremic state per se and is not related to a specific pathology of the kidney."}
{"id": "PMID:219973", "title": "Properties of a membrane-bound phosphatase activity in normal and abnormal red blood cells.", "content": "A neutral, membrane-bound, phosphatase activity was characterized in normal red blood cells, using p-nitrophenylphosphate as substrate. Its specific activity was 1.59 nmol mg-1 min-1. The kinetics were of the Michaelis type: KM,app = 2.5 X 10(-3) M. It was stimulated by K+ and inhibited by ouabain, a behaviour reminiscent of (Na+ + K+)-ATPase. In 10 patients with homozygous sickle cell disease and in 11 patients with unidentified congenital hemolytic anemias, the specific activity was significantly increased. In general, the phosphatase retained Michaelis-Menten kinetics. However, in four patients from the same family with an unidentified hemolytic anemia, the kinetics yielded a biphasic curve instead of a rectangular hyperbola, a change consistent with the existence of an inhibition by substrate excess. From detailed analysis of the curve, the apparent inhibitor constant for pNPP was determined: Ki,app approx. 2.5 X 10(-2) M. This novel abnormality of the red cell membrane might be the distinctive feature of a given type of congenital hemolytic anemia.", "contents": "Properties of a membrane-bound phosphatase activity in normal and abnormal red blood cells. A neutral, membrane-bound, phosphatase activity was characterized in normal red blood cells, using p-nitrophenylphosphate as substrate. Its specific activity was 1.59 nmol mg-1 min-1. The kinetics were of the Michaelis type: KM,app = 2.5 X 10(-3) M. It was stimulated by K+ and inhibited by ouabain, a behaviour reminiscent of (Na+ + K+)-ATPase. In 10 patients with homozygous sickle cell disease and in 11 patients with unidentified congenital hemolytic anemias, the specific activity was significantly increased. In general, the phosphatase retained Michaelis-Menten kinetics. However, in four patients from the same family with an unidentified hemolytic anemia, the kinetics yielded a biphasic curve instead of a rectangular hyperbola, a change consistent with the existence of an inhibition by substrate excess. From detailed analysis of the curve, the apparent inhibitor constant for pNPP was determined: Ki,app approx. 2.5 X 10(-2) M. This novel abnormality of the red cell membrane might be the distinctive feature of a given type of congenital hemolytic anemia."}
{"id": "PMID:219974", "title": "Acromegaly due to production of a growth hormone releasing factor by a bronchial carcinoid tumor.", "content": "We have studied growth hormone production in a patient with a bronchial carcinoid and acromegaly. The absence of growth hormone from the carcinoid tumour was demonstrated by extraction, cell culture and immunoperosidase techniques. Using a linked perfusion culture system, effluent from the bronchial carcinoid tumour culture stimulated a rapid release of growth hormone from a rat pituitary monolayer. This is the first time evidence of growth hormone releasing activity by a bronchial carcinoid has been demonstrated in a production.", "contents": "Acromegaly due to production of a growth hormone releasing factor by a bronchial carcinoid tumor. We have studied growth hormone production in a patient with a bronchial carcinoid and acromegaly. The absence of growth hormone from the carcinoid tumour was demonstrated by extraction, cell culture and immunoperosidase techniques. Using a linked perfusion culture system, effluent from the bronchial carcinoid tumour culture stimulated a rapid release of growth hormone from a rat pituitary monolayer. This is the first time evidence of growth hormone releasing activity by a bronchial carcinoid has been demonstrated in a production."}
{"id": "PMID:219975", "title": "Activation of the alternative pathway of complement by Entamoeba histolytica.", "content": "A cytopathogenic effect was observed when Entamoeba histolytica was exposed to human sera from individuals with no clinical history or laboratory evidence of amoebiasis. Absorption studies showed that the effect was not due to natural antibodies. Studies performed using ethylenediamine tetracetic acid (EDTA), cobra venom factor (CoF) and heat-inactivation at 56 degrees C, indicated that the cytopathogenic effect was complement dependent. Furthermore, by using ethylene glycol tetracetic acid (EGTA) and Mg++, zymosan, heat-inactivation at 50 degrees C to destroy the activity of factor B of the alternative pathway, as well as electrophoretic studies with anti-human factor B, it was possible to determine that E. histolytica activated the properdin pathway. Finally, complement determinations indicated that incubation of E. histolytica with normal human serum consumed complement. The diminution in CH50 correlated with a consumption of C3 but not of C1, C4 and C2. It was concluded from these results that trophozoites of E. histolytica activate the alternative pathway of the human complement system.", "contents": "Activation of the alternative pathway of complement by Entamoeba histolytica. A cytopathogenic effect was observed when Entamoeba histolytica was exposed to human sera from individuals with no clinical history or laboratory evidence of amoebiasis. Absorption studies showed that the effect was not due to natural antibodies. Studies performed using ethylenediamine tetracetic acid (EDTA), cobra venom factor (CoF) and heat-inactivation at 56 degrees C, indicated that the cytopathogenic effect was complement dependent. Furthermore, by using ethylene glycol tetracetic acid (EGTA) and Mg++, zymosan, heat-inactivation at 50 degrees C to destroy the activity of factor B of the alternative pathway, as well as electrophoretic studies with anti-human factor B, it was possible to determine that E. histolytica activated the properdin pathway. Finally, complement determinations indicated that incubation of E. histolytica with normal human serum consumed complement. The diminution in CH50 correlated with a consumption of C3 but not of C1, C4 and C2. It was concluded from these results that trophozoites of E. histolytica activate the alternative pathway of the human complement system."}
{"id": "PMID:219976", "title": "Epstein-Barr virus-related antibody patterns in ataxia-telangiectasia.", "content": "Epstein-Barr virus-related antibody titres were determined in twenty-seven patients with ataxia-telangiectasia (AT) and twenty-two healthy members of their families, in twenty-two patients with other diseases, among them ten with Beh\u00e7et's disease and ten with various primary immune deficiencies, and fifteen healthy members of their families, and in twenty-three unrelated healthy controls. The AT patients showed an increased incidence (55.6%) of high antibody titres (greater than or equal to 1:320) to viral capsid antigen (VCA), and also a high incidence (48.2%) of antibodies to Epstein-Barr virus (EBV) induced early antigens (EA), but low titres (less than 1:10) of antibodies to the EBV-associated nuclear antigen (EBNA) in 44.2% of the cases. The geometric means of anti-VCA were three-to four-fold higher, and of anti-EBNA six-fold lower, than those of the control groups. The patients with the other diseases did not differ significantly from the controls except for a higher incidence of anti-EBNA titres of less than 1:10 (38.1% vs 4--5%). AT patients with low anti-EBNA titres tended to have more advanced T cell deficiencies than AT patients with moderate anti-EBNA titres, as detected by counts of total lymphocytes and E-rosetting cells, and skin test responses. The results support the hypothesis that a functioning T cell system is required to release EBNA from EBV genome-carrying cells for initial and maintained production of anti-EBNA.", "contents": "Epstein-Barr virus-related antibody patterns in ataxia-telangiectasia. Epstein-Barr virus-related antibody titres were determined in twenty-seven patients with ataxia-telangiectasia (AT) and twenty-two healthy members of their families, in twenty-two patients with other diseases, among them ten with Beh\u00e7et's disease and ten with various primary immune deficiencies, and fifteen healthy members of their families, and in twenty-three unrelated healthy controls. The AT patients showed an increased incidence (55.6%) of high antibody titres (greater than or equal to 1:320) to viral capsid antigen (VCA), and also a high incidence (48.2%) of antibodies to Epstein-Barr virus (EBV) induced early antigens (EA), but low titres (less than 1:10) of antibodies to the EBV-associated nuclear antigen (EBNA) in 44.2% of the cases. The geometric means of anti-VCA were three-to four-fold higher, and of anti-EBNA six-fold lower, than those of the control groups. The patients with the other diseases did not differ significantly from the controls except for a higher incidence of anti-EBNA titres of less than 1:10 (38.1% vs 4--5%). AT patients with low anti-EBNA titres tended to have more advanced T cell deficiencies than AT patients with moderate anti-EBNA titres, as detected by counts of total lymphocytes and E-rosetting cells, and skin test responses. The results support the hypothesis that a functioning T cell system is required to release EBNA from EBV genome-carrying cells for initial and maintained production of anti-EBNA."}
{"id": "PMID:219981", "title": "LRC Coronary Prevention Trial: Baltimore.", "content": "Intense, initial efforts to enroll 250 individuals in the Coronary Prevention Trial at Johns Hopkins University through referrals from private physicians and from commercial laboratories were largely unsuccessful. Not until a mass-screening effort was initiated in the community were we able to contact sufficient nunbers of potential study candidates. The time needed to acquire the trial candidates was 2.5 times as long as our original estimate, and 35,000 individuals were tested in the process.", "contents": "LRC Coronary Prevention Trial: Baltimore. Intense, initial efforts to enroll 250 individuals in the Coronary Prevention Trial at Johns Hopkins University through referrals from private physicians and from commercial laboratories were largely unsuccessful. Not until a mass-screening effort was initiated in the community were we able to contact sufficient nunbers of potential study candidates. The time needed to acquire the trial candidates was 2.5 times as long as our original estimate, and 35,000 individuals were tested in the process."}
{"id": "PMID:219982", "title": "Treatment of Cushing's disease with adrenal blocking drugs and megavoltage therapy to the pituitary.", "content": "Eighteen patients with Cushing's disease were seen over a 40-month period and considered for treatment by pituitary irradiation and adrenal blocking drugs. Fourteen patients entered the study and each received megavoltage therapy to give a mean dose of 4600 rad to the pituitary over 31 days. Each patient was treated for one (two patients) or two (12 patients) years with one or both of the adrenocortical enzyme inhibitors, metyrapone or aminoglutethmide to suppress cortisol secretion. Doses were adjusted to maintain urinary free cortisol secretion below 300 nmol/24 h. One patient failed to complete the trial. Normal urinary free cortisol excretion and plasma cortisol concentration were maintained after treatment in eight of the remaining 13 patients after therapy. Only one patient required cortisol replacement and normal menstrual function was restored in five of the six women. The remaining five patients relapsed and four were subsequently treated by total adrenalectomy. It was noted that the patients who responded to treatment were substantially younger than the therapeutic failures. It is suggested that this treatment is most useful in the management of younger patients.", "contents": "Treatment of Cushing's disease with adrenal blocking drugs and megavoltage therapy to the pituitary. Eighteen patients with Cushing's disease were seen over a 40-month period and considered for treatment by pituitary irradiation and adrenal blocking drugs. Fourteen patients entered the study and each received megavoltage therapy to give a mean dose of 4600 rad to the pituitary over 31 days. Each patient was treated for one (two patients) or two (12 patients) years with one or both of the adrenocortical enzyme inhibitors, metyrapone or aminoglutethmide to suppress cortisol secretion. Doses were adjusted to maintain urinary free cortisol secretion below 300 nmol/24 h. One patient failed to complete the trial. Normal urinary free cortisol excretion and plasma cortisol concentration were maintained after treatment in eight of the remaining 13 patients after therapy. Only one patient required cortisol replacement and normal menstrual function was restored in five of the six women. The remaining five patients relapsed and four were subsequently treated by total adrenalectomy. It was noted that the patients who responded to treatment were substantially younger than the therapeutic failures. It is suggested that this treatment is most useful in the management of younger patients."}
{"id": "PMID:219983", "title": "Combined total body irradiation and local radiation therapy in oat cell carcinoma of the bronchus.", "content": "Use of total body irradiation (TBI) as a systematic therapy has been evaluated in controlling subclinical and established metastases in oat cell bronchus carcinoma. Preliminary results suggest that patients without clinical evidence of distant metastases do better than those with metastases. No patient in this series developed brain metastases. This could be related to TBI but may again be just a coincidence. The booster radiation dose (1000 rad) given to the liver seems to be inadequate in preventing metastases there, as all the deaths were due to liver metastases. In view of this, a higher dose to the liver is recommended.", "contents": "Combined total body irradiation and local radiation therapy in oat cell carcinoma of the bronchus. Use of total body irradiation (TBI) as a systematic therapy has been evaluated in controlling subclinical and established metastases in oat cell bronchus carcinoma. Preliminary results suggest that patients without clinical evidence of distant metastases do better than those with metastases. No patient in this series developed brain metastases. This could be related to TBI but may again be just a coincidence. The booster radiation dose (1000 rad) given to the liver seems to be inadequate in preventing metastases there, as all the deaths were due to liver metastases. In view of this, a higher dose to the liver is recommended."}
{"id": "PMID:219984", "title": "Non-function in nephroblastoma (Wilms's tumour): a report on the excretory urography of nine cases.", "content": "Non-function of a kidney invaded by nephroblastoma has not been extensively documented and may be featured only when a relatively large series is reviewed. It occurred in nine (15.5%) of 58 cases seen over an eight year period. Two of these nine cases had bilateral involvement and one showed curvilinear calcification. The mechanism of non-function appears to be due to replacement of most of the kidney substance by tumour, and this may be augmented by invasion of the renal pelvis causing malignant hydronephrosis. Ultrasonography has become increasingly utilised in confirming the diagnosis of renal tumours, but arteriography may still be the critical examination in the 'unusual' case.", "contents": "Non-function in nephroblastoma (Wilms's tumour): a report on the excretory urography of nine cases. Non-function of a kidney invaded by nephroblastoma has not been extensively documented and may be featured only when a relatively large series is reviewed. It occurred in nine (15.5%) of 58 cases seen over an eight year period. Two of these nine cases had bilateral involvement and one showed curvilinear calcification. The mechanism of non-function appears to be due to replacement of most of the kidney substance by tumour, and this may be augmented by invasion of the renal pelvis causing malignant hydronephrosis. Ultrasonography has become increasingly utilised in confirming the diagnosis of renal tumours, but arteriography may still be the critical examination in the 'unusual' case."}
{"id": "PMID:219986", "title": "Effects of glucocorticoid deficiency on renal medullary cyclic adenosine monophosphate of rats.", "content": "1. The effects of adrenalectomy on the adenylate cyclase--adenosine 3':5'-cyclic monophosphate (cyclic AMP) system of rat renal medulla were examined to evaluate the mechanism of the impaired water diuresis in glucocorticoid deficiency. 2. Concentrations of cyclic AMP in medullary tubules from adrenalectomized rats were significantly higher than in the tubules from control animals both in the presence and absence of antidiuretic hormone. 3. This abnormality was corrected by the treatment in vivo of the adrenalectomized rats with dexamethasone, but addition of this drug to the incubation medium did not abolish the differences in cyclic AMP between tubules from adrenalectomized and normal rats. 4. The activity of adenylate cyclase or cyclic AMP phosphodiesterase in vitro was not affected by adrenalectomy. 5. In glucocorticoid deficiency, the concentration of cyclic AMP in medullary tubules is increased both with and without antidiuretic hormone. This abnormality may render medullary tubules more permeable to water and may underlie the impaired water diuresis in glucocorticoid deficiency.", "contents": "Effects of glucocorticoid deficiency on renal medullary cyclic adenosine monophosphate of rats. 1. The effects of adrenalectomy on the adenylate cyclase--adenosine 3':5'-cyclic monophosphate (cyclic AMP) system of rat renal medulla were examined to evaluate the mechanism of the impaired water diuresis in glucocorticoid deficiency. 2. Concentrations of cyclic AMP in medullary tubules from adrenalectomized rats were significantly higher than in the tubules from control animals both in the presence and absence of antidiuretic hormone. 3. This abnormality was corrected by the treatment in vivo of the adrenalectomized rats with dexamethasone, but addition of this drug to the incubation medium did not abolish the differences in cyclic AMP between tubules from adrenalectomized and normal rats. 4. The activity of adenylate cyclase or cyclic AMP phosphodiesterase in vitro was not affected by adrenalectomy. 5. In glucocorticoid deficiency, the concentration of cyclic AMP in medullary tubules is increased both with and without antidiuretic hormone. This abnormality may render medullary tubules more permeable to water and may underlie the impaired water diuresis in glucocorticoid deficiency."}
{"id": "PMID:219988", "title": "Clinical trial with testosterone undecanoate for male fertility control.", "content": "The newly available orally effective testosterone undecanoate (TU) was investigated as a possible means for male fertility control. One of 7 normal volunteers exposed to 80 mg TU three times a day for 10-12 weeks became azoospermic, the remaining showed slightly suppressed or unaffected sperm counts. The insufficient suppression of spermatogenesis in 6 out of 7 subjects may be due to the fact that testosterone levels are only sufficiently high to suppress gonadotropins for some hours after ingestion of the drug.", "contents": "Clinical trial with testosterone undecanoate for male fertility control. The newly available orally effective testosterone undecanoate (TU) was investigated as a possible means for male fertility control. One of 7 normal volunteers exposed to 80 mg TU three times a day for 10-12 weeks became azoospermic, the remaining showed slightly suppressed or unaffected sperm counts. The insufficient suppression of spermatogenesis in 6 out of 7 subjects may be due to the fact that testosterone levels are only sufficiently high to suppress gonadotropins for some hours after ingestion of the drug."}
{"id": "PMID:219989", "title": "Pituitary hormones and amnesia.", "content": "Pituitary hormones profoundly influence behavior through direct actions on the brain. One of these behavioral effects is the attenuation of experimental amnesia. Traditionally, amnesia is considered as a \"loss of memory.\" Memory comprises at least 2 stages: input (memory consolidation) and output (memory retrieval). Theoretically, disturbance of either aspect of memory may be the cause of amnesia. Also, it is possible that amnesia is based on a factor or factors not related to memory. Data and theories on amnesia in man were reviewed. Some salient features were mentioned: (1) amnesia can be induced by a variety of agents; (2) amnesia covers periods ranging from seconds to years; (3) amnesia gradients can be established; (4) amnesia is to a large extent reversible. From this survey, it seems possible that amnesia is not a homogeneous phenomenon and that even in one person a disturbance of both memory consolidation and memory retrieval may be produced by one and the same event. Animal studies in general have confirmed these conclusions. We have developed an animal model in order to study the effects of pituitary peptides on amnesia. This model is based on CO2-induced amnesia for a one-trial passive avoidance response in rats. This amnesia could be attenuated by treatment with ACTH-analogs 1 hour before the retrieval test. This anti-amnesic effect of ACTH-analogs was not dependent on the nature of the behavioral response or the amnesic treatment. The vasopressin-analog DGLVP similarly exerted an anti-amnesic effect when injected before the retrieval trial. In contrast to ACTH-analogs, however, it also reduced the amnesia when injected before acquisition. These results suggest that amnesia may comprise a \"faulty-consolidation\" and a \"faulty-retrieval\" component, which may be amended by different pituitary hormones. The study of the anti-amnesic activity of peptides therefore not only serves to characterize the nature of the behavioral effect of these peptides but may also prove to be helpful of the unraveling of processes involved in amnesia.", "contents": "Pituitary hormones and amnesia. Pituitary hormones profoundly influence behavior through direct actions on the brain. One of these behavioral effects is the attenuation of experimental amnesia. Traditionally, amnesia is considered as a \"loss of memory.\" Memory comprises at least 2 stages: input (memory consolidation) and output (memory retrieval). Theoretically, disturbance of either aspect of memory may be the cause of amnesia. Also, it is possible that amnesia is based on a factor or factors not related to memory. Data and theories on amnesia in man were reviewed. Some salient features were mentioned: (1) amnesia can be induced by a variety of agents; (2) amnesia covers periods ranging from seconds to years; (3) amnesia gradients can be established; (4) amnesia is to a large extent reversible. From this survey, it seems possible that amnesia is not a homogeneous phenomenon and that even in one person a disturbance of both memory consolidation and memory retrieval may be produced by one and the same event. Animal studies in general have confirmed these conclusions. We have developed an animal model in order to study the effects of pituitary peptides on amnesia. This model is based on CO2-induced amnesia for a one-trial passive avoidance response in rats. This amnesia could be attenuated by treatment with ACTH-analogs 1 hour before the retrieval test. This anti-amnesic effect of ACTH-analogs was not dependent on the nature of the behavioral response or the amnesic treatment. The vasopressin-analog DGLVP similarly exerted an anti-amnesic effect when injected before the retrieval trial. In contrast to ACTH-analogs, however, it also reduced the amnesia when injected before acquisition. These results suggest that amnesia may comprise a \"faulty-consolidation\" and a \"faulty-retrieval\" component, which may be amended by different pituitary hormones. The study of the anti-amnesic activity of peptides therefore not only serves to characterize the nature of the behavioral effect of these peptides but may also prove to be helpful of the unraveling of processes involved in amnesia."}
{"id": "PMID:219990", "title": "Regional asssignments of the loci AK3, ACONS, and ASS on human chromosome 9.", "content": "Experiments are described in which human cells carrying balanced reciprocal translocations involving four different regions of chromosome 9 were fused with a Chinese hamster cell line and the resulting hybrids used to obtain subchromosomal assignments of the loci ASS, AK3, and ACONS. ASS was localized on the distal portion of the long arm of chromosome 9, in the region 9q34 leads to 9qter, and AK3 and ACONS on the short arm, in the region 9pter leads to 9p13.", "contents": "Regional asssignments of the loci AK3, ACONS, and ASS on human chromosome 9. Experiments are described in which human cells carrying balanced reciprocal translocations involving four different regions of chromosome 9 were fused with a Chinese hamster cell line and the resulting hybrids used to obtain subchromosomal assignments of the loci ASS, AK3, and ACONS. ASS was localized on the distal portion of the long arm of chromosome 9, in the region 9q34 leads to 9qter, and AK3 and ACONS on the short arm, in the region 9pter leads to 9p13."}
{"id": "PMID:220001", "title": "[Early auditory evoked potentials, triggered by a sine-wave stimulus (author's transl)].", "content": "Within the first 10 ms after a sine-shaped sound wave (tone pip) seven small-amplitude potentials can be recorded in persons with normal hearing and normal brainstem functions. These components, in the nanovolt range, correspond to the electrical activity of various pathways of the auditory tract. In accordance with this view the resulting potentials were assigned to the following structures in the region of the periphery and the brainstem: component I corresponds to the cochlea or acoustic nerve (receptor, II to the cochlear nucleus (medulla), III to the upper olive (caudal pons), IV to the lateral lemniscus (rostral pons), V to the inferior colliculus (midbrain), VI to the medial geniculate body (diencephalon), VII to the acoustic radiation (cortex). Clinically well defined lesions of the acoustic nerve and brainstem indicate that there is a close topographical relationship between the clinical localisation and absence or delay of the individual components.", "contents": "[Early auditory evoked potentials, triggered by a sine-wave stimulus (author's transl)]. Within the first 10 ms after a sine-shaped sound wave (tone pip) seven small-amplitude potentials can be recorded in persons with normal hearing and normal brainstem functions. These components, in the nanovolt range, correspond to the electrical activity of various pathways of the auditory tract. In accordance with this view the resulting potentials were assigned to the following structures in the region of the periphery and the brainstem: component I corresponds to the cochlea or acoustic nerve (receptor, II to the cochlear nucleus (medulla), III to the upper olive (caudal pons), IV to the lateral lemniscus (rostral pons), V to the inferior colliculus (midbrain), VI to the medial geniculate body (diencephalon), VII to the acoustic radiation (cortex). Clinically well defined lesions of the acoustic nerve and brainstem indicate that there is a close topographical relationship between the clinical localisation and absence or delay of the individual components."}
{"id": "PMID:220003", "title": "Photosensitive epilepsy in Papio papio as a model for drug studies.", "content": "Photically-induced epilepsy in Papio papio provides a convenient model for assessing the efficacy and the acute neurological toxicity of new anticonvulsant drugs prior to clinical trial. Its drug sensitivity is broadly comparable to that of generalized seizures in man. It also shares some specific properties with syndromes of reflex epilepsy in man.", "contents": "Photosensitive epilepsy in Papio papio as a model for drug studies. Photically-induced epilepsy in Papio papio provides a convenient model for assessing the efficacy and the acute neurological toxicity of new anticonvulsant drugs prior to clinical trial. Its drug sensitivity is broadly comparable to that of generalized seizures in man. It also shares some specific properties with syndromes of reflex epilepsy in man."}
{"id": "PMID:220004", "title": "The physiological interpretation of electrical stimulation of the nervous system.", "content": "The physiological basis of the responses of cells in the nervous system to electrical stimulation is described by reference to the strength-duration curve and to the characteristics of ion-carriers in the cell membranes. The effects of the electrode systems used to deliver the electrical stimuli are considered briefly, followed by an account of the relative electrical excitability of nervous elements in peripheral nerves, spinal cord and the cellular nuclei of the nervous system. The responses of more complex physiological systems to both peripheral and central electrical stimulation are then considered, with more detailed reference to neural mechanisms involved in analgesia at peripheral, spinal and brain-stem levels.", "contents": "The physiological interpretation of electrical stimulation of the nervous system. The physiological basis of the responses of cells in the nervous system to electrical stimulation is described by reference to the strength-duration curve and to the characteristics of ion-carriers in the cell membranes. The effects of the electrode systems used to deliver the electrical stimuli are considered briefly, followed by an account of the relative electrical excitability of nervous elements in peripheral nerves, spinal cord and the cellular nuclei of the nervous system. The responses of more complex physiological systems to both peripheral and central electrical stimulation are then considered, with more detailed reference to neural mechanisms involved in analgesia at peripheral, spinal and brain-stem levels."}
{"id": "PMID:220005", "title": "Functional electrical stimulation in control of motor output and movements.", "content": "In patient with damaged upper motor neurones we show the therapeutic effect of electrical stimulation (called FES) of peripheral mixed nerves on the restoration of motor activity and movements. The results of neurophysiological, kinesiological and clinical observations are presented. We discuss the possible mechanisms, especially the spinal ones, which are fundamental for such a rhythmic activity as gait. We discuss them also from the point of view of activation of proprioceptive feedback mechanisms and of achieved sensory reinforcement influencing the spinal reflex mechanisms as well as the preserved supraspinal integrated activity which contributes to the long-term FES effect. The stimulation modes, the control of stimuli in relation to the needs of individual patients (hemiplegia in adults, paraparesis, cerebral palsy in children and multiple sclerosis) as well as the motor deficit are discussed. We conclude that the electronic system used for this purpose represents a functionally active orthotic aid with therapeutic effects.", "contents": "Functional electrical stimulation in control of motor output and movements. In patient with damaged upper motor neurones we show the therapeutic effect of electrical stimulation (called FES) of peripheral mixed nerves on the restoration of motor activity and movements. The results of neurophysiological, kinesiological and clinical observations are presented. We discuss the possible mechanisms, especially the spinal ones, which are fundamental for such a rhythmic activity as gait. We discuss them also from the point of view of activation of proprioceptive feedback mechanisms and of achieved sensory reinforcement influencing the spinal reflex mechanisms as well as the preserved supraspinal integrated activity which contributes to the long-term FES effect. The stimulation modes, the control of stimuli in relation to the needs of individual patients (hemiplegia in adults, paraparesis, cerebral palsy in children and multiple sclerosis) as well as the motor deficit are discussed. We conclude that the electronic system used for this purpose represents a functionally active orthotic aid with therapeutic effects."}
{"id": "PMID:220006", "title": "Polyneuropathy. Facts and fancies.", "content": "Some conclusions are drawn from findings in 167 consecutive patients with the ordinary \"garden variety\" of polyneuropathy; the aetiology was unknown in 15%. Histological findings in sural nerves were related to clinical and electrophysiological abnormalities. In some patients with discrete clinical abnormalities, sensory and motor conduction and amplitudes of evoked sensory and muscle action potentials were normal, whereas the nerve biopsy showed slight but definite abnormalities. The reverse, abnormal nerve conduction and normal histological findings, did not occur. Histological findings were rarely, and electrophysiological findings were not, specific for the aetiology or type of a neuropathy. Thus, neither conduction studies nor conventional or single fibre electromyography can identify the underlying pathology: loss of large myelinated fibres (greater than 7 micrometers) was equally prominent in nerves with de- and re-myelination as in those without them. Paranodal and segmental demyelination in less than 20% of the teased fibres occurred as often in nerves with as in those without disproportionate slowing in conduction. When the recorded conduction velocity was equal to that to be expected from the fibres with the largest diameter, slowing in conduction could be explained by axonal degeneration (\"proportionate\" slowing, 79% of the nerves). When the recorded velocity was disproportionately slower than that expected from fibre diameter (21% of the nerves), causes other than loss of the largest fibres must be assumed to explain the slowing in conduction. Myelin abnormalities in more than 50% of the teased fibres were found only in nerves from patients with the hypertrophic type of peroneal muscular atrophy and in postgastrectomy neuropathy and can probably explain the marked disproportionate slowing in conduction. The material contained, however, only one patient with acute idiopathic polyradiculoneuropahy. In diabetic neuropathy, segmental demyelination was present in only 8 of 502 teased fibres (9 nerves), remyelination was present in 135 fibres, and could not explain the disproportionate slowing in conduction. The mechanism of disproportionate slowing, when it is not due to demyelination, is still obscure.", "contents": "Polyneuropathy. Facts and fancies. Some conclusions are drawn from findings in 167 consecutive patients with the ordinary \"garden variety\" of polyneuropathy; the aetiology was unknown in 15%. Histological findings in sural nerves were related to clinical and electrophysiological abnormalities. In some patients with discrete clinical abnormalities, sensory and motor conduction and amplitudes of evoked sensory and muscle action potentials were normal, whereas the nerve biopsy showed slight but definite abnormalities. The reverse, abnormal nerve conduction and normal histological findings, did not occur. Histological findings were rarely, and electrophysiological findings were not, specific for the aetiology or type of a neuropathy. Thus, neither conduction studies nor conventional or single fibre electromyography can identify the underlying pathology: loss of large myelinated fibres (greater than 7 micrometers) was equally prominent in nerves with de- and re-myelination as in those without them. Paranodal and segmental demyelination in less than 20% of the teased fibres occurred as often in nerves with as in those without disproportionate slowing in conduction. When the recorded conduction velocity was equal to that to be expected from the fibres with the largest diameter, slowing in conduction could be explained by axonal degeneration (\"proportionate\" slowing, 79% of the nerves). When the recorded velocity was disproportionately slower than that expected from fibre diameter (21% of the nerves), causes other than loss of the largest fibres must be assumed to explain the slowing in conduction. Myelin abnormalities in more than 50% of the teased fibres were found only in nerves from patients with the hypertrophic type of peroneal muscular atrophy and in postgastrectomy neuropathy and can probably explain the marked disproportionate slowing in conduction. The material contained, however, only one patient with acute idiopathic polyradiculoneuropahy. In diabetic neuropathy, segmental demyelination was present in only 8 of 502 teased fibres (9 nerves), remyelination was present in 135 fibres, and could not explain the disproportionate slowing in conduction. The mechanism of disproportionate slowing, when it is not due to demyelination, is still obscure."}
{"id": "PMID:220007", "title": "Structure-function correlations in myasthenia gravis and a new myasthenic syndrome.", "content": "The physiologic hallmark of MG is the small amplitude of the mepp. This can be correlated with a deficiency of postsynaptic AChR. The AChR deficiency is caused by antiAChR antibodies. Antibody dependent, complement mediated lysis of the postsynaptic membrane contributes significantly to the AChR deficiency. The abundance of immune complexes localized at the end-plate correlates with the amount of AChR remaining at the end-plate and with the mepp amplitude. The physiologic hallmarks of the new myasthenic syndrome are a small quantum content of the end-plate potential due to a decreased store of immediately releasable quanta, repetitive response of the muscle to a single nerve stimulus and refractoriness to anticholinesterase drugs. The findings are explained by a marked decrease of the size of the nerve terminal and by the total absence of AChE from the end-plate.", "contents": "Structure-function correlations in myasthenia gravis and a new myasthenic syndrome. The physiologic hallmark of MG is the small amplitude of the mepp. This can be correlated with a deficiency of postsynaptic AChR. The AChR deficiency is caused by antiAChR antibodies. Antibody dependent, complement mediated lysis of the postsynaptic membrane contributes significantly to the AChR deficiency. The abundance of immune complexes localized at the end-plate correlates with the amount of AChR remaining at the end-plate and with the mepp amplitude. The physiologic hallmarks of the new myasthenic syndrome are a small quantum content of the end-plate potential due to a decreased store of immediately releasable quanta, repetitive response of the muscle to a single nerve stimulus and refractoriness to anticholinesterase drugs. The findings are explained by a marked decrease of the size of the nerve terminal and by the total absence of AChE from the end-plate."}
{"id": "PMID:220011", "title": "Corticoliberin (CRF) activity of the rat neurohypophysis.", "content": "Corticoliberin (CRF) activity of the rat stalk-median eminence region (SME) and neural lobe of the pituitary (NL) was tested in vitro using cultured cells of anterior pituitary. The activity of NL was found to be more than 50% lower than that of SME. The parallelism of dose-response curves suggests that corticotropin releasing substances originating from NL and SME may be qualitatively identical. Thus, neurosecretory cells producing corticoliberin seem to form a continuous neurohemal system consisting of the median eminence, the stalk of the neural lobe.", "contents": "Corticoliberin (CRF) activity of the rat neurohypophysis. Corticoliberin (CRF) activity of the rat stalk-median eminence region (SME) and neural lobe of the pituitary (NL) was tested in vitro using cultured cells of anterior pituitary. The activity of NL was found to be more than 50% lower than that of SME. The parallelism of dose-response curves suggests that corticotropin releasing substances originating from NL and SME may be qualitatively identical. Thus, neurosecretory cells producing corticoliberin seem to form a continuous neurohemal system consisting of the median eminence, the stalk of the neural lobe."}
{"id": "PMID:220012", "title": "Basal levels of pituitary ACTH and plasma corticosterone after complete or frontal cuts around medial basal hypothalamus.", "content": "Plasma corticosterone level and corticotropin (ACTH) content of the anterior pituitary (AP) were measured after various cuts around the medial basal hypothalamus (MBH). Seven to eight days after placing a complete cut around MBH there was no change in plasma corticosterone or ACTH content of AP; the slight rise in ACTH concentration was offset by the decreased weight of AP. Twenty eight days after a frontal cut there was no change in plasma corticosterone and in bioactive or immunoreactive ACTH concentration of AP.", "contents": "Basal levels of pituitary ACTH and plasma corticosterone after complete or frontal cuts around medial basal hypothalamus. Plasma corticosterone level and corticotropin (ACTH) content of the anterior pituitary (AP) were measured after various cuts around the medial basal hypothalamus (MBH). Seven to eight days after placing a complete cut around MBH there was no change in plasma corticosterone or ACTH content of AP; the slight rise in ACTH concentration was offset by the decreased weight of AP. Twenty eight days after a frontal cut there was no change in plasma corticosterone and in bioactive or immunoreactive ACTH concentration of AP."}
{"id": "PMID:220013", "title": "A case of pituitary adrenocorticotropin-dependent Cushing's syndrome in the horse.", "content": "In the horse, a syndrome of hirsutism, hyperglycemia, glucosuria, polydipsia, polyuria, polyphagia, and progressive debilitation has been recognized. Most often the syndrome has been associated with adenomas of the pars intermedia of the pituitary and bilateral adrenal hyperplasia or nodular hyperplasia involving primarily the zona fasciculata. Previously, the syndrome has been ascribed to compression of the hypothalamus by an expanding but functionally inactive pituitary neoplasm. In the present case, with RIA determination of plasma ACTH concentrations, the syndrome was ascribed to pituitary ACTH-dependent hyperadrenocorticism and likened to human Cushing's disease.", "contents": "A case of pituitary adrenocorticotropin-dependent Cushing's syndrome in the horse. In the horse, a syndrome of hirsutism, hyperglycemia, glucosuria, polydipsia, polyuria, polyphagia, and progressive debilitation has been recognized. Most often the syndrome has been associated with adenomas of the pars intermedia of the pituitary and bilateral adrenal hyperplasia or nodular hyperplasia involving primarily the zona fasciculata. Previously, the syndrome has been ascribed to compression of the hypothalamus by an expanding but functionally inactive pituitary neoplasm. In the present case, with RIA determination of plasma ACTH concentrations, the syndrome was ascribed to pituitary ACTH-dependent hyperadrenocorticism and likened to human Cushing's disease."}
{"id": "PMID:220014", "title": "Low density lipoprotein receptors in bovine adrenal cortex. I. Receptor-mediated uptake of low density lipoprotein and utilization of its cholesterol for steroid synthesis in cultured adrenocortical cells.", "content": "Functioning bovine adrenocortical cells in monolayer culture were shown to obtain cholesterol for steroid synthesis from plasma low density lipoprotein (LDL). When grown in medium devoid of lipoproteins, the cells developed a minimal enhancement in steroid secretion in response to ACTH or cholera toxin. However, when LDL was available, steroid secretion was stimulated 4- to 9-fold. To determine the mechanism for this effect, we used LDL in which the protein component was labeled with 125I and the cholesteryl ester component was labeled with [3H]cholesteryl linoleate. These studies demonstrated that the cells derived cholesterol from LDL by binding the lipoprotein at a high affinity receptor site, internalizing it, and hydrolyzing its cholesteryl esters within lysosomes. The resultant free cholesterol was used for steroid synthesis and also acted to suppress the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase and cholesterol synthesis within the cell. LDL receptor activity was enhanced several-fold by treatment of the cells with ACTH or cholera toxin. High density lipoprotein, which did not bind to the LDL receptor, was not degraded with high affinity by the cells and did not support steroid synthesis. The current data suggest that the bovine adrenal cortex can obtain cholesterol for steroid hormone secretion from circulating LDL by means of a high affinity LDL receptor pathway. In a subsequent paper in this series, a similar high affinity LDL-binding site is demonstrated in membranes prepared from fresh bovine adrenocortical tissue.", "contents": "Low density lipoprotein receptors in bovine adrenal cortex. I. Receptor-mediated uptake of low density lipoprotein and utilization of its cholesterol for steroid synthesis in cultured adrenocortical cells. Functioning bovine adrenocortical cells in monolayer culture were shown to obtain cholesterol for steroid synthesis from plasma low density lipoprotein (LDL). When grown in medium devoid of lipoproteins, the cells developed a minimal enhancement in steroid secretion in response to ACTH or cholera toxin. However, when LDL was available, steroid secretion was stimulated 4- to 9-fold. To determine the mechanism for this effect, we used LDL in which the protein component was labeled with 125I and the cholesteryl ester component was labeled with [3H]cholesteryl linoleate. These studies demonstrated that the cells derived cholesterol from LDL by binding the lipoprotein at a high affinity receptor site, internalizing it, and hydrolyzing its cholesteryl esters within lysosomes. The resultant free cholesterol was used for steroid synthesis and also acted to suppress the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase and cholesterol synthesis within the cell. LDL receptor activity was enhanced several-fold by treatment of the cells with ACTH or cholera toxin. High density lipoprotein, which did not bind to the LDL receptor, was not degraded with high affinity by the cells and did not support steroid synthesis. The current data suggest that the bovine adrenal cortex can obtain cholesterol for steroid hormone secretion from circulating LDL by means of a high affinity LDL receptor pathway. In a subsequent paper in this series, a similar high affinity LDL-binding site is demonstrated in membranes prepared from fresh bovine adrenocortical tissue."}
{"id": "PMID:220015", "title": "Low density lipoprotein receptors in bovine adrenal cortex. II. Low density lipoprotein binding to membranes prepared from fresh tissue.", "content": "Low density lipoprotein (LDL)-binding activity was measured in whole homogenates and membranes prepared from fresh bovine adrenal cortex by an ultracentrifugation assay. The binding site for 125I-labeled LDL in isolated membranes shared the properties of the LDL receptor previously demonstrated in intact monolayers of cultured bovine adrenocortical cells. The amount of high affinity [125I]iodo-LDL-binding activity in the adrenal cortex was 6- to 12-fold higher than in the medulla of the same glands. Large amounts of high affinity [125I]iodo-LDL-binding activity were also present in the ovarian corpus luteum but not in the ovarian interstitium. Lesser amounts of high affinity binding activity were observed in 14 other bovine tissues. These results lend support to the concept that cells in the bovine adrenal cortex can obtain cholesterol for steroid hormone synthesis through the receptor-mediated uptake of plasma LDL.", "contents": "Low density lipoprotein receptors in bovine adrenal cortex. II. Low density lipoprotein binding to membranes prepared from fresh tissue. Low density lipoprotein (LDL)-binding activity was measured in whole homogenates and membranes prepared from fresh bovine adrenal cortex by an ultracentrifugation assay. The binding site for 125I-labeled LDL in isolated membranes shared the properties of the LDL receptor previously demonstrated in intact monolayers of cultured bovine adrenocortical cells. The amount of high affinity [125I]iodo-LDL-binding activity in the adrenal cortex was 6- to 12-fold higher than in the medulla of the same glands. Large amounts of high affinity [125I]iodo-LDL-binding activity were also present in the ovarian corpus luteum but not in the ovarian interstitium. Lesser amounts of high affinity binding activity were observed in 14 other bovine tissues. These results lend support to the concept that cells in the bovine adrenal cortex can obtain cholesterol for steroid hormone synthesis through the receptor-mediated uptake of plasma LDL."}
{"id": "PMID:220016", "title": "Effects of diamide on basal and thyrotropin-stimulated thyroid metabolism.", "content": "The effect of diamide on basal and TSH-stimulated thyroid metabolism was studied using bovine and dog thyroid slices. Diamide (10 mM) inhibited basal and TSH-stimulated net cAMP production, basal and cAMP-stimulated protein kinase activity, and stimulation by TSH of colloid droplet formation and organification of iodide and abolished basal and TSH-stimulated uptake of 32P into phospholipids. In thyroid slices incubated with 0.1 mM diamide, none of these activities, whether basal or TSH-stimulated, was affected. However, 0.1 mM diamide increased the net basal production of cAMP and potentiated the effect of TSH on this process. These results demonstrate that the previously reported inhibition of protein kinase by 2-20 mM diamide is not specific and that this compound cannot be used to determine which of the metabolic effects of TSH are dependent upon cAMP activation of protein kinase. While 0.1 mM diamide increased cAMP in thyroid slices, it did not reproduce any of the other effects of TSH.", "contents": "Effects of diamide on basal and thyrotropin-stimulated thyroid metabolism. The effect of diamide on basal and TSH-stimulated thyroid metabolism was studied using bovine and dog thyroid slices. Diamide (10 mM) inhibited basal and TSH-stimulated net cAMP production, basal and cAMP-stimulated protein kinase activity, and stimulation by TSH of colloid droplet formation and organification of iodide and abolished basal and TSH-stimulated uptake of 32P into phospholipids. In thyroid slices incubated with 0.1 mM diamide, none of these activities, whether basal or TSH-stimulated, was affected. However, 0.1 mM diamide increased the net basal production of cAMP and potentiated the effect of TSH on this process. These results demonstrate that the previously reported inhibition of protein kinase by 2-20 mM diamide is not specific and that this compound cannot be used to determine which of the metabolic effects of TSH are dependent upon cAMP activation of protein kinase. While 0.1 mM diamide increased cAMP in thyroid slices, it did not reproduce any of the other effects of TSH."}
{"id": "PMID:220017", "title": "Somatostatin secretion from monolayer cultures of neonatal rat pancreas.", "content": "Monolayer cultures of neonatal rat pancreas have been characterized as an in vitro system for studying SRIF secretion. Marked 12- and 6-fold potentiation of SRIF release occurred with N-2-O-dibutyryl cAMP monosodium salt and theophylline, respectively. High glucose (300 mg/dl) stimulated SRIF release, whereas galactose was without effect. Exogenous insulin did not alter SRIF release, and the SRIF responses to theophylline and glucose were unaffected by the addition of antiinsulin serum to neutralize the insulin released by these agents. Arginine evoked a significant 2-fold increase in SRIF release. Exogenous glucagon produced slight but not significant stimulation of SRIF release. However, after exposure of the cultures to antiglucagon serum to diminish the concentration of glucagon in contact with the SRIF cells, exogenous glucagon produced a marked enhancement of SRIF secretion. These data suggest that glucose, arginine, glucagon, N-2-O-dibutyryl cAMP monosodium salt, and theophylline stimulate SRIF secretion, probably by direct effects on D cells or through mechanisms other than increased insulin secretion. Monolayer cultures of rat pancreas should provide a powerful in vitro system for studying pancreatic SRIF physiology.", "contents": "Somatostatin secretion from monolayer cultures of neonatal rat pancreas. Monolayer cultures of neonatal rat pancreas have been characterized as an in vitro system for studying SRIF secretion. Marked 12- and 6-fold potentiation of SRIF release occurred with N-2-O-dibutyryl cAMP monosodium salt and theophylline, respectively. High glucose (300 mg/dl) stimulated SRIF release, whereas galactose was without effect. Exogenous insulin did not alter SRIF release, and the SRIF responses to theophylline and glucose were unaffected by the addition of antiinsulin serum to neutralize the insulin released by these agents. Arginine evoked a significant 2-fold increase in SRIF release. Exogenous glucagon produced slight but not significant stimulation of SRIF release. However, after exposure of the cultures to antiglucagon serum to diminish the concentration of glucagon in contact with the SRIF cells, exogenous glucagon produced a marked enhancement of SRIF secretion. These data suggest that glucose, arginine, glucagon, N-2-O-dibutyryl cAMP monosodium salt, and theophylline stimulate SRIF secretion, probably by direct effects on D cells or through mechanisms other than increased insulin secretion. Monolayer cultures of rat pancreas should provide a powerful in vitro system for studying pancreatic SRIF physiology."}
{"id": "PMID:220027", "title": "Inhibition of the pituitary-adrenal response to stress during deprivation-induced feeding.", "content": "Plasma corticosterone and plasma and pituitary ACTH concentrations were determined during feeding and after application of an acute stress at various times after food and water presentation to male rats maintained on a restricted feeding and watering schedule. Both plasma corticosterone and ACTH concentrations fell after the presentation of food and water, and this fall was accompanied by increased levels of ACTH in the pituitary gland. In addition, a rise in plasma levels of ACTH was inhibited in response to an acute stress applied at 0--5 min after presentation of food and water, but ACTH synthesis was not. This inhibition of ACTH and corticosterone secretion in response to stress was transient and dissipated as a relatively linear function of the interval between food presentation and application of the stress. The results suggest that this feeding-induced, corticosteroid-independent inhibition of pituitary-adrenal activity involves active inhibitory mechanisms operating initially on ACTH secretory processes of the pituitary and later on the synthesis of ACTH or on the secretion of hypothalamic corticotropin-releasing factor.", "contents": "Inhibition of the pituitary-adrenal response to stress during deprivation-induced feeding. Plasma corticosterone and plasma and pituitary ACTH concentrations were determined during feeding and after application of an acute stress at various times after food and water presentation to male rats maintained on a restricted feeding and watering schedule. Both plasma corticosterone and ACTH concentrations fell after the presentation of food and water, and this fall was accompanied by increased levels of ACTH in the pituitary gland. In addition, a rise in plasma levels of ACTH was inhibited in response to an acute stress applied at 0--5 min after presentation of food and water, but ACTH synthesis was not. This inhibition of ACTH and corticosterone secretion in response to stress was transient and dissipated as a relatively linear function of the interval between food presentation and application of the stress. The results suggest that this feeding-induced, corticosteroid-independent inhibition of pituitary-adrenal activity involves active inhibitory mechanisms operating initially on ACTH secretory processes of the pituitary and later on the synthesis of ACTH or on the secretion of hypothalamic corticotropin-releasing factor."}
{"id": "PMID:220028", "title": "Molecular weight forms of adrenocorticotropic hormone secreted by primary cultures of mouse anterior pituitary.", "content": "Extracts of mouse anterior pituitary cells in monolayer culture were subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis to separate the molecular weight forms of ACTH. The gels were sliced and each segment was eluted. The eluates were assayed for ACTH immunoactivity. Approximately 10% of the immunoactivity in the extracts was found to be present as 20,000--32,000 mol wt ACTH. The remainder of the immunoactivity was equally distributed between two forms of ACTH with apparent molecular weights of 11,800 and 4,500. This distribution is very similar to that found in extracts of mouse anterior pituitary. Mouse anterior pituitary cultures were incubated for 2 h in serum-free tissue culture medium. ACTH was concentrated from the medium and fractionated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The medium was found to contain predominantly the 4,500 and 11,800 forms of ACTH. When vasopressin was added to these cultures (100 ng/ml), the rate of secretion of ACTH was more than doubled in serum free medium. Analysis of the medium from vasopressin-stimulated cultures showed that the 4,500 and 11,800 mol wt forms of ACTH were again the predominant forms present.", "contents": "Molecular weight forms of adrenocorticotropic hormone secreted by primary cultures of mouse anterior pituitary. Extracts of mouse anterior pituitary cells in monolayer culture were subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis to separate the molecular weight forms of ACTH. The gels were sliced and each segment was eluted. The eluates were assayed for ACTH immunoactivity. Approximately 10% of the immunoactivity in the extracts was found to be present as 20,000--32,000 mol wt ACTH. The remainder of the immunoactivity was equally distributed between two forms of ACTH with apparent molecular weights of 11,800 and 4,500. This distribution is very similar to that found in extracts of mouse anterior pituitary. Mouse anterior pituitary cultures were incubated for 2 h in serum-free tissue culture medium. ACTH was concentrated from the medium and fractionated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The medium was found to contain predominantly the 4,500 and 11,800 forms of ACTH. When vasopressin was added to these cultures (100 ng/ml), the rate of secretion of ACTH was more than doubled in serum free medium. Analysis of the medium from vasopressin-stimulated cultures showed that the 4,500 and 11,800 mol wt forms of ACTH were again the predominant forms present."}
{"id": "PMID:220030", "title": "Mechanism of action of prolactin on adrenocortical steroid secretion in hypophysectomized female rats.", "content": "Studies were carried out to determine the actions of PRL on adrenocortical function in hypophysectomized female rats in the presence and absence of ACTH. PRL administration alone decreased 5 alpha-reductase activity but did not significantly affect the rates of corticosterone secretion or peripheral plasma corticosterone concentrations. The activities of several steroidogenic enzymes (cholesterol desmolase, 11 beta-hydroxylase, and 21-hydroxylase) were also unaffected by PRL. Adrenal steroidogenesis was increased by ACTH treatment, as expected, resulting in an increase in corticosterone secretion. However, since adrenal 5 alpha-reductase activity was higher in ACTH-treated hypophysectomized rats than in normal animals with intact pituitary glands, large amounts of 5 alpha-dihydrocorticosterone (DHB) and 3 beta, 5 alpha-tetrahydrocorticosterone (THB) were also secreted. PRL, when administered in combination with ACTH, potentiated the effecte levels. PRL did not affect cholesterol side chain cleavage, 11 beta-hydroxylation, or 21-hydroxylation in ACTH-treated rats. However, administration of PRL to ACTH-treated rats lowered adrenal 5 alpha-reductase activity, decreasing DHB and THB secretion. The decrease in DHB and THB secretion approximated the increase in corticosterone output. The results indicate that, in the presence of ACTH, PRL increases corticosterone secretion by decreasing intraadrenal degradation of corticosterone and not by enhancing steroidogenesis.", "contents": "Mechanism of action of prolactin on adrenocortical steroid secretion in hypophysectomized female rats. Studies were carried out to determine the actions of PRL on adrenocortical function in hypophysectomized female rats in the presence and absence of ACTH. PRL administration alone decreased 5 alpha-reductase activity but did not significantly affect the rates of corticosterone secretion or peripheral plasma corticosterone concentrations. The activities of several steroidogenic enzymes (cholesterol desmolase, 11 beta-hydroxylase, and 21-hydroxylase) were also unaffected by PRL. Adrenal steroidogenesis was increased by ACTH treatment, as expected, resulting in an increase in corticosterone secretion. However, since adrenal 5 alpha-reductase activity was higher in ACTH-treated hypophysectomized rats than in normal animals with intact pituitary glands, large amounts of 5 alpha-dihydrocorticosterone (DHB) and 3 beta, 5 alpha-tetrahydrocorticosterone (THB) were also secreted. PRL, when administered in combination with ACTH, potentiated the effecte levels. PRL did not affect cholesterol side chain cleavage, 11 beta-hydroxylation, or 21-hydroxylation in ACTH-treated rats. However, administration of PRL to ACTH-treated rats lowered adrenal 5 alpha-reductase activity, decreasing DHB and THB secretion. The decrease in DHB and THB secretion approximated the increase in corticosterone output. The results indicate that, in the presence of ACTH, PRL increases corticosterone secretion by decreasing intraadrenal degradation of corticosterone and not by enhancing steroidogenesis."}
{"id": "PMID:220031", "title": "Antiestrogen inhibits the induction of progestin receptors by estradiol in the hypothalamus-preoptic area and pituitary.", "content": "Estradiol treatment of ovariectomized-adrenalectomized rats produced an increase in cytosol progestin binding in the hypothalamus-preoptic area (HPOA), pituitary, and uterus. In the HPOA and pituitary, this induction of progestin receptors by estradiol was inhibited by the antiestrogen CI-628 under a variety of dose and time conditions. In the uterus, inhibition of the full effect of estradiol on progestin binding was observed after 3 days of injection of antiestrogen and estradiol. In the absence of estradiol, the antiestrogen produced a slight induction of progestin receptors in the HPOA and pituitary and a substantial induction of progestin receptors in the uterus. The results suggest that the induction of progestin receptors could be a key intermediate step in some behavioral and neuroendocrine actions of estradiol.", "contents": "Antiestrogen inhibits the induction of progestin receptors by estradiol in the hypothalamus-preoptic area and pituitary. Estradiol treatment of ovariectomized-adrenalectomized rats produced an increase in cytosol progestin binding in the hypothalamus-preoptic area (HPOA), pituitary, and uterus. In the HPOA and pituitary, this induction of progestin receptors by estradiol was inhibited by the antiestrogen CI-628 under a variety of dose and time conditions. In the uterus, inhibition of the full effect of estradiol on progestin binding was observed after 3 days of injection of antiestrogen and estradiol. In the absence of estradiol, the antiestrogen produced a slight induction of progestin receptors in the HPOA and pituitary and a substantial induction of progestin receptors in the uterus. The results suggest that the induction of progestin receptors could be a key intermediate step in some behavioral and neuroendocrine actions of estradiol."}
{"id": "PMID:220032", "title": "Inhibitory effects of long term treatment with a luteinizing hormone-releasing hormone agonist on the pituitary-gonadal axis in male and female rats.", "content": "Following previous observations of the potent antifertility effects of acute treatment with LHRH or its agonistic analogs in male and female rats, this study describes the effect of long term (up to 12 weeks) treatment with an LHRH agonist, [D-Ala6, des-Gly-NH210]LHRH ethylamide (LHRH-A), on testicular and ovarian gonadotropin receptor levels and function in the rat. Treatment of adult male rats with 100 ng LHRH-A every third day led to a progressive decrease of testis, seminal vesicle, and prostate weight up to 12 weeks of treatment, while the inhibitory effect (70%) on LH receptor levels was already maximal at 1 week. When adult female rats were injected daily with 5 microgram LHRH-A for 12 weeks, ovarian LH, FSH, and PRL receptor levels were reduced 50--90%, while plasma estradiol and progesterone levels were inhibited 60% (compared with diestrus day 1). The effect of chronic administration of a low dose (5 IU) of hCG in the male rat was transient. By contrast, no sign of resistance developed up to 12 weeks of treatment with the LHRH agonist in either male or female animals.", "contents": "Inhibitory effects of long term treatment with a luteinizing hormone-releasing hormone agonist on the pituitary-gonadal axis in male and female rats. Following previous observations of the potent antifertility effects of acute treatment with LHRH or its agonistic analogs in male and female rats, this study describes the effect of long term (up to 12 weeks) treatment with an LHRH agonist, [D-Ala6, des-Gly-NH210]LHRH ethylamide (LHRH-A), on testicular and ovarian gonadotropin receptor levels and function in the rat. Treatment of adult male rats with 100 ng LHRH-A every third day led to a progressive decrease of testis, seminal vesicle, and prostate weight up to 12 weeks of treatment, while the inhibitory effect (70%) on LH receptor levels was already maximal at 1 week. When adult female rats were injected daily with 5 microgram LHRH-A for 12 weeks, ovarian LH, FSH, and PRL receptor levels were reduced 50--90%, while plasma estradiol and progesterone levels were inhibited 60% (compared with diestrus day 1). The effect of chronic administration of a low dose (5 IU) of hCG in the male rat was transient. By contrast, no sign of resistance developed up to 12 weeks of treatment with the LHRH agonist in either male or female animals."}
{"id": "PMID:220035", "title": "Immunohistochemical localization of adrenocorticotropin in the rat brain.", "content": "ACTH and some of its fragments have been shown to play a role in a variety of adaptative mechanisms. To clearly identify the nervous structures containing ACTH in the rat brain, an immunohistochemical localization of this peptide was conducted at both light and electron microscopic levels. Nervous fibers staining for ACTH were found to be largely distributed throughout regions of hypothalamus, thalamus, and midbrain. Positive fibers could also be occasionally observed in the spinal cord. Immunostained neuronal cell bodies were only detected in the arcuate nucleus. Essentially, the same results were obtained 2 and 8 weeks after hypophysectomy. In animals pretreated with colchicine, the intensity in the staining of cell bodies was markedly increased, making possible the detection of a larger number of cell bodies. At the electron microscopic level, it was demonstrated that ACTH is contained in dense core vesicles present in nervous fibers and endings. These results indicate that ACTH of nonpituitary origin is synthesized in the central nervous system and could probably be considered as a neurotransmitter of still undefined function.", "contents": "Immunohistochemical localization of adrenocorticotropin in the rat brain. ACTH and some of its fragments have been shown to play a role in a variety of adaptative mechanisms. To clearly identify the nervous structures containing ACTH in the rat brain, an immunohistochemical localization of this peptide was conducted at both light and electron microscopic levels. Nervous fibers staining for ACTH were found to be largely distributed throughout regions of hypothalamus, thalamus, and midbrain. Positive fibers could also be occasionally observed in the spinal cord. Immunostained neuronal cell bodies were only detected in the arcuate nucleus. Essentially, the same results were obtained 2 and 8 weeks after hypophysectomy. In animals pretreated with colchicine, the intensity in the staining of cell bodies was markedly increased, making possible the detection of a larger number of cell bodies. At the electron microscopic level, it was demonstrated that ACTH is contained in dense core vesicles present in nervous fibers and endings. These results indicate that ACTH of nonpituitary origin is synthesized in the central nervous system and could probably be considered as a neurotransmitter of still undefined function."}
{"id": "PMID:220036", "title": "Glucocorticoid regulation of prolactin receptors on mammary cells in culture.", "content": "Mouse mammary epithelial cultures were examined for the ability to specifically bind [125I]PRL after cultivation on floating collagen gels. Corticosterone, particularly hydrocortisone, were effective in increasing the ability of mouse mammary cells to bind [125I]PRL. The absence of a glucocorticoid in the medium resulted in a loss of PRL binding during the 3 days in culture. 17 beta-Estradiol, progesterone, and aldosterone at equal molar concentration had no or only a small effect in increasing [125I]PRL binding.", "contents": "Glucocorticoid regulation of prolactin receptors on mammary cells in culture. Mouse mammary epithelial cultures were examined for the ability to specifically bind [125I]PRL after cultivation on floating collagen gels. Corticosterone, particularly hydrocortisone, were effective in increasing the ability of mouse mammary cells to bind [125I]PRL. The absence of a glucocorticoid in the medium resulted in a loss of PRL binding during the 3 days in culture. 17 beta-Estradiol, progesterone, and aldosterone at equal molar concentration had no or only a small effect in increasing [125I]PRL binding."}
{"id": "PMID:220037", "title": "Luteinizing hormone-releasing hormone inactivation by purified pituitary plasma membranes: effects of receptor-binding studies.", "content": "Inactivation of LHRH by purified bovine pituitary plasma membranes was studied in vitro. After incubation of [125I]iodo-LHRH with plasma membranes, the amount of tracer bound to the pellet was measured, and the integrity of the unbound tracer in the supernatant was assessed. Reduction in ability to bind to anti-LHRH serum and to rebind to plasma membranes together with altered electrophoretic mobility on polyacrylamide gels showed that the unbound [125I]iodo-LHRH was inactivated. LHRH inactivation occurred rapidly and was dependent upon membrane concentration and incubation temperature. These results indicate that hormone inactivation must be taken into account in the interpretation of LHRH-receptor interactions. During 37 C incubations, the apparent absence of specific LHRH binding can be explained by inactivation of tracer hormone. Significant LHRH inactivation also occurred at 0 C, which in part explains the insensitivity of LHRH receptor assays. Assessment of LHRH inactivation by different particulate subcellular fractions of pituitary tissue showed that the inactivating enzyme was associated with the plasma membranes; other organelles did not alter LHRH. The enzyme appeared to be an integral part of the plasma membrane structure, since enzymic activity could not be removed by washing without reducing specific LHRH binding. Additionally, reduction of LHRH inactivation by the inhibitors Bacitracin and Trasylol and by magnesium was also accompanied by reduced LHRH binding. Previous studies have shown that the majority of LHRH binding to pituitary plasma membranes is to the low affinity site (approximately 10(-6) M), but the significance of this binding has been uncertain. Our findings indicate that low affinity binding probably represents binding of LHRH to the inactivating enzyme. The LHRH analog, D-Ser6(TBu), des Gly10, ethylamide, has greater biological activity than LHRH and is not inactivated to a significant extent by pituitary plasma membranes. The enhanced biological activity of the analog, therefore, may be due to its resistance to inactivation by enzymes on the pituitary cell surface. The membrane-associated inactivating enzyme could play an important role in vivo in determining the concentration of intact LHRH available at the receptor site which initiates gonadotropin release.", "contents": "Luteinizing hormone-releasing hormone inactivation by purified pituitary plasma membranes: effects of receptor-binding studies. Inactivation of LHRH by purified bovine pituitary plasma membranes was studied in vitro. After incubation of [125I]iodo-LHRH with plasma membranes, the amount of tracer bound to the pellet was measured, and the integrity of the unbound tracer in the supernatant was assessed. Reduction in ability to bind to anti-LHRH serum and to rebind to plasma membranes together with altered electrophoretic mobility on polyacrylamide gels showed that the unbound [125I]iodo-LHRH was inactivated. LHRH inactivation occurred rapidly and was dependent upon membrane concentration and incubation temperature. These results indicate that hormone inactivation must be taken into account in the interpretation of LHRH-receptor interactions. During 37 C incubations, the apparent absence of specific LHRH binding can be explained by inactivation of tracer hormone. Significant LHRH inactivation also occurred at 0 C, which in part explains the insensitivity of LHRH receptor assays. Assessment of LHRH inactivation by different particulate subcellular fractions of pituitary tissue showed that the inactivating enzyme was associated with the plasma membranes; other organelles did not alter LHRH. The enzyme appeared to be an integral part of the plasma membrane structure, since enzymic activity could not be removed by washing without reducing specific LHRH binding. Additionally, reduction of LHRH inactivation by the inhibitors Bacitracin and Trasylol and by magnesium was also accompanied by reduced LHRH binding. Previous studies have shown that the majority of LHRH binding to pituitary plasma membranes is to the low affinity site (approximately 10(-6) M), but the significance of this binding has been uncertain. Our findings indicate that low affinity binding probably represents binding of LHRH to the inactivating enzyme. The LHRH analog, D-Ser6(TBu), des Gly10, ethylamide, has greater biological activity than LHRH and is not inactivated to a significant extent by pituitary plasma membranes. The enhanced biological activity of the analog, therefore, may be due to its resistance to inactivation by enzymes on the pituitary cell surface. The membrane-associated inactivating enzyme could play an important role in vivo in determining the concentration of intact LHRH available at the receptor site which initiates gonadotropin release."}
{"id": "PMID:220039", "title": "An attempt to analyze various thyroid stimulators by the receptor assay using hTSH radioimmunoassay.", "content": "In an attempt to analyze thyroid stimulators in serum we developed an assay procedure using hTSH radioimmunoassay (RIA) in combination with receptor competition. The principle of this method is the determination by RIA of hTSH displaced by other thyroid stimulators from a thyroidal receptor preparation which previously bound unlabelled hTSH. Practically 4 microunits of hTSH were bound with human or bovine receptor, and then hTSH displaced by addition of test serum (0.1 ml) or samples dissolved in serum (0.1 ml) was measured by RIA. This assay can determine the thyroid stimulators other than hTSH in serum that has the displacement activity of 0.5-4.0 microunits of hTSH in the useful range, such as mU/ml level of bovine TSH or rat TSH. Cholera toxin that has the thyroid stimulating activity like TSH also showed the displacement of the bound hTSH. This assay is not applicable for the human serum with more than 5 microunits/ml of TSH, because the assay value is over estimated by the free hTSH derived from the test serum. On the other hand, eighteen sera with high LATS activity and 42 sera with negative LATS activity from patients with untreated hyperthyroidism did not show any displacement. This might be due to the lower binding activity of LATS with hTSH receptor or the lower sensitivity of this assay method. Although it is difficult to use this assay clinically because of its low sensitivity, increased TSH in animal serum can be determined by this assay. The principle of this method may be also useful for examining the receptor binding of other peptide hormone that can be determined by an RIA method.", "contents": "An attempt to analyze various thyroid stimulators by the receptor assay using hTSH radioimmunoassay. In an attempt to analyze thyroid stimulators in serum we developed an assay procedure using hTSH radioimmunoassay (RIA) in combination with receptor competition. The principle of this method is the determination by RIA of hTSH displaced by other thyroid stimulators from a thyroidal receptor preparation which previously bound unlabelled hTSH. Practically 4 microunits of hTSH were bound with human or bovine receptor, and then hTSH displaced by addition of test serum (0.1 ml) or samples dissolved in serum (0.1 ml) was measured by RIA. This assay can determine the thyroid stimulators other than hTSH in serum that has the displacement activity of 0.5-4.0 microunits of hTSH in the useful range, such as mU/ml level of bovine TSH or rat TSH. Cholera toxin that has the thyroid stimulating activity like TSH also showed the displacement of the bound hTSH. This assay is not applicable for the human serum with more than 5 microunits/ml of TSH, because the assay value is over estimated by the free hTSH derived from the test serum. On the other hand, eighteen sera with high LATS activity and 42 sera with negative LATS activity from patients with untreated hyperthyroidism did not show any displacement. This might be due to the lower binding activity of LATS with hTSH receptor or the lower sensitivity of this assay method. Although it is difficult to use this assay clinically because of its low sensitivity, increased TSH in animal serum can be determined by this assay. The principle of this method may be also useful for examining the receptor binding of other peptide hormone that can be determined by an RIA method."}
{"id": "PMID:220040", "title": "Comparative study of cyclic AMP-generation system, steroid biosynthesis and lipid metabolism in vitro in ACTH responsive and unresponsive adrenal tumors.", "content": "The responses of the cyclic AMP-generation system and corticosteroids biosynthesis to ACTH and angiotensin II and cholesterol and other lipid contents in adrenal tissues were estimated in the in vitro experiments in 3 cases of Cushing's syndrome due to ACTH-responsive and unresponsive adenomas, one case of Cushing's disease (diffuse hyperplasia), one case of primary aldosteronism and one normal subject. The responses of cAMP accumulation and corticosteroids production to ACTH in in vitro studies were quite in good agreement with the in vivo responses of plasma cortisol by ACTH infusion test. The adenylate cyclase activity decreased and the phosphodiesterase activity increased in the case of hyperplasia and in one case of ACTH-responsive adenoma, whereas the basal cyclic AMP content was slightly more in ACTH-responsive adenoma and maximal in hyperplasia compared with that of the normal adrenal tissue. The characteristic features observed in ACTH-unresponsive adenoma were the largest amount of the basal corticosteroids production and esterified cholesterol content, and the lowest content cAMP. These results indicate that there was not always the consistent correlation between the cAMP-generation system, corticosteroids and aldosterone production, and conversion of cholesterol to pregnenolone by the stimulation of ACTH and angiotensin II in adrenal tumors.", "contents": "Comparative study of cyclic AMP-generation system, steroid biosynthesis and lipid metabolism in vitro in ACTH responsive and unresponsive adrenal tumors. The responses of the cyclic AMP-generation system and corticosteroids biosynthesis to ACTH and angiotensin II and cholesterol and other lipid contents in adrenal tissues were estimated in the in vitro experiments in 3 cases of Cushing's syndrome due to ACTH-responsive and unresponsive adenomas, one case of Cushing's disease (diffuse hyperplasia), one case of primary aldosteronism and one normal subject. The responses of cAMP accumulation and corticosteroids production to ACTH in in vitro studies were quite in good agreement with the in vivo responses of plasma cortisol by ACTH infusion test. The adenylate cyclase activity decreased and the phosphodiesterase activity increased in the case of hyperplasia and in one case of ACTH-responsive adenoma, whereas the basal cyclic AMP content was slightly more in ACTH-responsive adenoma and maximal in hyperplasia compared with that of the normal adrenal tissue. The characteristic features observed in ACTH-unresponsive adenoma were the largest amount of the basal corticosteroids production and esterified cholesterol content, and the lowest content cAMP. These results indicate that there was not always the consistent correlation between the cAMP-generation system, corticosteroids and aldosterone production, and conversion of cholesterol to pregnenolone by the stimulation of ACTH and angiotensin II in adrenal tumors."}
{"id": "PMID:220041", "title": "Relationship between 5'-nucleotidase, adenosine deaminase, AMP deaminase, ATP-(Mg2+)-ase activities and dTMP kinase activity in rat liver mitochondria.", "content": "The activities of dTMP kinase (ATP-deoxythymidine monophosphate phosphotransferase, EC 2.7.4.9), 5'-nucleotidase (5'-ribonucleoside phosphohydrolase, EC 3.1.3.5), adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4), AMP deaminase (AMP aminohydrolase, EC 3.5.3.6) and ATP-(Mg2+)-ase (ATP phosphohydrolase, EC 3.6.1.3) were assayed in mitochondria of normal and regenerating rat liver. In regenerating mitochondria, the dTMP kinase activity increased 20 times, 5'-nucleotidase (5'Nase) activity for dTMP diminished by 65% and its activity for other nucleoside monophosphates did not change; adenosine deaminase activity for adenosine (AR) increased by 40%, but for deoxyadenosine (AdR) decreased by 70%. AMP deaminase and ATP-(Mg2+)-ase activities behaved similarly in mitochondria from regenerating liver, decreasing by 70 and 64% respectively. The changes of the amount of dTMP in mitochondria depend on enzyme activities which regulate the AdR concentration.", "contents": "Relationship between 5'-nucleotidase, adenosine deaminase, AMP deaminase, ATP-(Mg2+)-ase activities and dTMP kinase activity in rat liver mitochondria. The activities of dTMP kinase (ATP-deoxythymidine monophosphate phosphotransferase, EC 2.7.4.9), 5'-nucleotidase (5'-ribonucleoside phosphohydrolase, EC 3.1.3.5), adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4), AMP deaminase (AMP aminohydrolase, EC 3.5.3.6) and ATP-(Mg2+)-ase (ATP phosphohydrolase, EC 3.6.1.3) were assayed in mitochondria of normal and regenerating rat liver. In regenerating mitochondria, the dTMP kinase activity increased 20 times, 5'-nucleotidase (5'Nase) activity for dTMP diminished by 65% and its activity for other nucleoside monophosphates did not change; adenosine deaminase activity for adenosine (AR) increased by 40%, but for deoxyadenosine (AdR) decreased by 70%. AMP deaminase and ATP-(Mg2+)-ase activities behaved similarly in mitochondria from regenerating liver, decreasing by 70 and 64% respectively. The changes of the amount of dTMP in mitochondria depend on enzyme activities which regulate the AdR concentration."}
{"id": "PMID:220042", "title": "Liver and kidney glucose-6-phosphatase levels in carbon tetrachloride- and DDT-administered mice.", "content": "Mouse liver and kidney glucose-6-phosphatase levels were found to be decreased 24 h after administration of various doses of carbon tetrachloride (CCl4) when compared to controls. Liver glucose-6-phosphatase levels were always decreased to a greater extent than the kidney enzyme in mice given the same amount of CCl4. Administration of p,p'-1,1,1,-trichloro-2,2-bis (p-chlorophenyl) ethane (p,p'-DDT) to mice did not significantly alter the glucose-6-phosphatase levels of liver or kidney.", "contents": "Liver and kidney glucose-6-phosphatase levels in carbon tetrachloride- and DDT-administered mice. Mouse liver and kidney glucose-6-phosphatase levels were found to be decreased 24 h after administration of various doses of carbon tetrachloride (CCl4) when compared to controls. Liver glucose-6-phosphatase levels were always decreased to a greater extent than the kidney enzyme in mice given the same amount of CCl4. Administration of p,p'-1,1,1,-trichloro-2,2-bis (p-chlorophenyl) ethane (p,p'-DDT) to mice did not significantly alter the glucose-6-phosphatase levels of liver or kidney."}
{"id": "PMID:220043", "title": "Localization of the high-affinity ATP site in adenosine-3':5'-monophosphate-dependent protein kinase type I. Photoaffinity labelling studies with 8-azidoadenosine 5'-triphosphate.", "content": "8-Azido-adenosine 5'-triphosphate (n8(3)ATP) appeared to be a suitable photoaffinity label for the protein kinase dependent on adenosine 3':5'-monophosphate (cAMP). It competes with ATP for the high-affinity ATP site in the undissociated form of the kinase and in the phosphotransferase reaction catalyzed by the catalytic subunit. Furthermore, it is accepted as a substrate in the phosphotransfer reaction. n8(3)ATP incorporated into the holoenzyme is covalently bound irradiation. Protection experiments with ATP indicated that this covalent attachment occurs in the high-affinity ATP site of the enzyme. Polyacrylamide gel electrophoresis in the presence of sodium dodecylsulfate shows that n8(3)ATP is bound to the catalytic subunit. After irradiation the enzyme was dissociated by cAMP. Proportional to the incorporated [gamma-32P]n8(3)ATP, a loss in phosphotransferase activity was found. These results support our model that both ATP sites coincide with respect to their adenine binding part. Thus binding of the regulatory subunit to the catalytic subunit would then transform the low-affinity catalytically active ATP site into a high-affinity inactive site.", "contents": "Localization of the high-affinity ATP site in adenosine-3':5'-monophosphate-dependent protein kinase type I. Photoaffinity labelling studies with 8-azidoadenosine 5'-triphosphate. 8-Azido-adenosine 5'-triphosphate (n8(3)ATP) appeared to be a suitable photoaffinity label for the protein kinase dependent on adenosine 3':5'-monophosphate (cAMP). It competes with ATP for the high-affinity ATP site in the undissociated form of the kinase and in the phosphotransferase reaction catalyzed by the catalytic subunit. Furthermore, it is accepted as a substrate in the phosphotransfer reaction. n8(3)ATP incorporated into the holoenzyme is covalently bound irradiation. Protection experiments with ATP indicated that this covalent attachment occurs in the high-affinity ATP site of the enzyme. Polyacrylamide gel electrophoresis in the presence of sodium dodecylsulfate shows that n8(3)ATP is bound to the catalytic subunit. After irradiation the enzyme was dissociated by cAMP. Proportional to the incorporated [gamma-32P]n8(3)ATP, a loss in phosphotransferase activity was found. These results support our model that both ATP sites coincide with respect to their adenine binding part. Thus binding of the regulatory subunit to the catalytic subunit would then transform the low-affinity catalytically active ATP site into a high-affinity inactive site."}
{"id": "PMID:220044", "title": "Distribution of the messenger RNA coding for the common precursor of corticotropin and beta-lipotropin within the bovine pituitary.", "content": "The distribution of the mRNA coding for the common precursor of corticotropin and beta-lipotropin among different parts of the bovine pituitary has been investigated by quantifying the mRNA activity with the use of a cell-free protein-synthesizing system. The results obtained have demonstrated that this mRNA activity is located both in the anterior lobe and in the intermediate lobe, while it is essentially not detectable in the neural lobe nor in the stalk. The structural identity of the translation products of corticotropin/beta-lipotropin mRNA from the anterior and from the intermediate lobe has been indicated by their molecular weight as well as by the electrophoretic patterns of the peptide fragments formed from them upon partial enzymatic proteolysis or upon cyanogen bromide cleavage. The specific activity of corticotropin/beta-lipotropin mRNA in the intermediate lobe is about 20-fold higher than that in the anterior lobe, and the total activity of this mRNA in the former is about 2-fold higher than that in the latter. In the intermediate lobe, the translation product of corticotropin/beta-lipotropin mRNA amounts to almost one-third of the products encoded by total translatable mRNA. These results indicate that corticotropin/beta-lipotropin mRNA represents a major mRNA species in intermediate lobe of the pituitary, thus suggesting that this lobe may perform a highly specialized function in producing a large amount of the common precursor of corticotropin and beta-lipotropin.", "contents": "Distribution of the messenger RNA coding for the common precursor of corticotropin and beta-lipotropin within the bovine pituitary. The distribution of the mRNA coding for the common precursor of corticotropin and beta-lipotropin among different parts of the bovine pituitary has been investigated by quantifying the mRNA activity with the use of a cell-free protein-synthesizing system. The results obtained have demonstrated that this mRNA activity is located both in the anterior lobe and in the intermediate lobe, while it is essentially not detectable in the neural lobe nor in the stalk. The structural identity of the translation products of corticotropin/beta-lipotropin mRNA from the anterior and from the intermediate lobe has been indicated by their molecular weight as well as by the electrophoretic patterns of the peptide fragments formed from them upon partial enzymatic proteolysis or upon cyanogen bromide cleavage. The specific activity of corticotropin/beta-lipotropin mRNA in the intermediate lobe is about 20-fold higher than that in the anterior lobe, and the total activity of this mRNA in the former is about 2-fold higher than that in the latter. In the intermediate lobe, the translation product of corticotropin/beta-lipotropin mRNA amounts to almost one-third of the products encoded by total translatable mRNA. These results indicate that corticotropin/beta-lipotropin mRNA represents a major mRNA species in intermediate lobe of the pituitary, thus suggesting that this lobe may perform a highly specialized function in producing a large amount of the common precursor of corticotropin and beta-lipotropin."}
{"id": "PMID:220045", "title": "Sialic-acid content of low-density lipoproteins controls their binding and uptake by cultured cells.", "content": "The (high-affinity receptor)-mediated uptake of homologous low-density (low-rho) lipoproteins by cultured human arterial smooth muscle cells or human skin fibroblasts is controlled by the sialic acid content of low-rho lipoprotein particles. This conclusion is derived from the following results. 1. Gangliosides incubated with native low-rho lipoproteins associate with low-rho lipoprotein particles. Low-rho lipoproteins modified by associated GLac1, GGtet1, and GGtet2b + GGtet3 gangliosides are internalized by arterial smooth muscle cells at a rate up to 80% lower than native low-rho lipoproteins or those preincubated with desialized gangliosides. 2. The inhibitory effect of gangliosides is specific for high affinity uptake and not detectable on skin fibroblasts deficient in low-rho-lipoprotein receptor. 3. Desialyzed low-rho lipoproteins are internalized by smooth muscle cells up to 100% faster than native low-rho lipoproteins, the enhancement of uptake corresponding to the degree of desialization.", "contents": "Sialic-acid content of low-density lipoproteins controls their binding and uptake by cultured cells. The (high-affinity receptor)-mediated uptake of homologous low-density (low-rho) lipoproteins by cultured human arterial smooth muscle cells or human skin fibroblasts is controlled by the sialic acid content of low-rho lipoprotein particles. This conclusion is derived from the following results. 1. Gangliosides incubated with native low-rho lipoproteins associate with low-rho lipoprotein particles. Low-rho lipoproteins modified by associated GLac1, GGtet1, and GGtet2b + GGtet3 gangliosides are internalized by arterial smooth muscle cells at a rate up to 80% lower than native low-rho lipoproteins or those preincubated with desialized gangliosides. 2. The inhibitory effect of gangliosides is specific for high affinity uptake and not detectable on skin fibroblasts deficient in low-rho-lipoprotein receptor. 3. Desialyzed low-rho lipoproteins are internalized by smooth muscle cells up to 100% faster than native low-rho lipoproteins, the enhancement of uptake corresponding to the degree of desialization."}
{"id": "PMID:220046", "title": "Affinity labelling of yeast and liver alcohol dehydrogenases with the NAD analogue 4-(3-bromoacetylpyridinio)butyldiphosphoadenosine.", "content": "The NAD analogue 4-(3-bromoacetylpyridinio)butyldiphosphoadenosine inactivates alcohol dehydrogenases from horse liver and yeast by modification of amino acid side chains at the active sites of the proteins. In the presence of excess inactivator the reaction is pseudo first order. The stoichiometry is one male inactivator incorporated per mole enzyme subunit. The liver enzyme is inactivated by ketoalkylation of the essential cysteine residue at position 46. No intermediate reactions of other residues are detected, and added cysteine does not influence the modification. In contrast, the labelling results with the yeast enzyme depend on cysteine treatment. The only radioactive peptide isolated is labelled on the essential cysteine residue 43.", "contents": "Affinity labelling of yeast and liver alcohol dehydrogenases with the NAD analogue 4-(3-bromoacetylpyridinio)butyldiphosphoadenosine. The NAD analogue 4-(3-bromoacetylpyridinio)butyldiphosphoadenosine inactivates alcohol dehydrogenases from horse liver and yeast by modification of amino acid side chains at the active sites of the proteins. In the presence of excess inactivator the reaction is pseudo first order. The stoichiometry is one male inactivator incorporated per mole enzyme subunit. The liver enzyme is inactivated by ketoalkylation of the essential cysteine residue at position 46. No intermediate reactions of other residues are detected, and added cysteine does not influence the modification. In contrast, the labelling results with the yeast enzyme depend on cysteine treatment. The only radioactive peptide isolated is labelled on the essential cysteine residue 43."}
{"id": "PMID:220047", "title": "Hydrophobic interactions of cytochrome c oxidase. Application to the purification of the enzyme from rat liver mitochondria.", "content": "The binding of rat liver cytochrome c oxidase to phenyl-Sepharose and various alkyl and omega-aminoalkyl agarose gels has been studied. Deoxycholate-solubilized cytochrome c oxidase was tightly bound to hexyl, octyl, omega-aminohexyl, omega-aminooctyl agarose as well as to phenyl-Sepharose. This hydrophobic interaction was used for the purification of cytochrome c oxidase. The enzyme which was eluted from phenyl-Sepharose was devoid of NADH (NADPH)-acceptor reductase activities. The heme a content was 15.4 nmol per mg of protein. The purified enzyme was resolved into seven polypeptides upon polyacrylamide gel electrophoresis in sodium dodecylsulfate with molecular weights of 40,000, 23,200, 21,500, 14,500, 12,600, 8900, and 4900. Antibodies raised in rabbits against the pure enzyme did not cross-react with cytochrome c oxidases from either beef heart or yeast mitochondria. Cytochrome c oxidase bound to octyl-Sepharose or phenyl-Sepharose exhibited a very low catalytic activity. The possible modes of interaction of cytochrome c oxidase with the hydrophobic ligands are discussed.", "contents": "Hydrophobic interactions of cytochrome c oxidase. Application to the purification of the enzyme from rat liver mitochondria. The binding of rat liver cytochrome c oxidase to phenyl-Sepharose and various alkyl and omega-aminoalkyl agarose gels has been studied. Deoxycholate-solubilized cytochrome c oxidase was tightly bound to hexyl, octyl, omega-aminohexyl, omega-aminooctyl agarose as well as to phenyl-Sepharose. This hydrophobic interaction was used for the purification of cytochrome c oxidase. The enzyme which was eluted from phenyl-Sepharose was devoid of NADH (NADPH)-acceptor reductase activities. The heme a content was 15.4 nmol per mg of protein. The purified enzyme was resolved into seven polypeptides upon polyacrylamide gel electrophoresis in sodium dodecylsulfate with molecular weights of 40,000, 23,200, 21,500, 14,500, 12,600, 8900, and 4900. Antibodies raised in rabbits against the pure enzyme did not cross-react with cytochrome c oxidases from either beef heart or yeast mitochondria. Cytochrome c oxidase bound to octyl-Sepharose or phenyl-Sepharose exhibited a very low catalytic activity. The possible modes of interaction of cytochrome c oxidase with the hydrophobic ligands are discussed."}
{"id": "PMID:220049", "title": "Tonic foot: clinical and neurophysiological study of a case.", "content": "A case of involuntary plantar flexion of the toes and sole with no other neurological pathological sign is reported. The electromyographic activity of some muscles of the involved limb. the behavior of the phenomenon during the sleep-wakefulness cycle and spinal reflex excitability have been studied. According to the clinical and neurophysiological findings, the phenomenon appears to be a dystonia. Such a dystonia may occur as the only pathological neurological sign or together with the other signs of central nervous system involvement. Particular care has to be taken to distinguish 'tonic foot' from hypertonus of sole flexor muscles occurring almost always in all spastic hemipareses.", "contents": "Tonic foot: clinical and neurophysiological study of a case. A case of involuntary plantar flexion of the toes and sole with no other neurological pathological sign is reported. The electromyographic activity of some muscles of the involved limb. the behavior of the phenomenon during the sleep-wakefulness cycle and spinal reflex excitability have been studied. According to the clinical and neurophysiological findings, the phenomenon appears to be a dystonia. Such a dystonia may occur as the only pathological neurological sign or together with the other signs of central nervous system involvement. Particular care has to be taken to distinguish 'tonic foot' from hypertonus of sole flexor muscles occurring almost always in all spastic hemipareses."}
{"id": "PMID:220050", "title": "Sleep electroencephalograms and sleep stages in hypoparathyroidism.", "content": "2 patients with hypoparathyroidism, one idiopathic and the other pseudoform, were studied by overnight polygraphic recording of the sleep EEG and related activities before and after start of treatment to investigate their sleep EEG patterns and states, with the results as follows. (1) Conspicuous abnormalities were noted in the sleep record, namely, disappearance of humps, spindles and hill waves, emergence of the mitten pattern and rather monotonous delta rhythm bursts. The EEGs, both awake and asleep, showed findings suggestive of a possible disorder of the desynchronizing mechanism of the brain stem. Normal sleep EEG patterns were restored after the serum calcium level had returned to the normal range. (2) In the course of overnight sleep, disturbance in the cyclic changes of sleep EEG pattern and absence of REM sleep were observed. Restoration to the normal course of sleep was achieved following the normalization of serum calcium level. Divalent calcium ion is considered to have intimate bearing upon the mechanism whereby synaptic chemical transmitters are activated. When viewed with reference to the monoamine hypothesis of Jouvet, the disturbance in the course of sleep observed in the present cases, especially the absence of or disturbed REM sleep, is inferred to be related to the hypocalcemia.", "contents": "Sleep electroencephalograms and sleep stages in hypoparathyroidism. 2 patients with hypoparathyroidism, one idiopathic and the other pseudoform, were studied by overnight polygraphic recording of the sleep EEG and related activities before and after start of treatment to investigate their sleep EEG patterns and states, with the results as follows. (1) Conspicuous abnormalities were noted in the sleep record, namely, disappearance of humps, spindles and hill waves, emergence of the mitten pattern and rather monotonous delta rhythm bursts. The EEGs, both awake and asleep, showed findings suggestive of a possible disorder of the desynchronizing mechanism of the brain stem. Normal sleep EEG patterns were restored after the serum calcium level had returned to the normal range. (2) In the course of overnight sleep, disturbance in the cyclic changes of sleep EEG pattern and absence of REM sleep were observed. Restoration to the normal course of sleep was achieved following the normalization of serum calcium level. Divalent calcium ion is considered to have intimate bearing upon the mechanism whereby synaptic chemical transmitters are activated. When viewed with reference to the monoamine hypothesis of Jouvet, the disturbance in the course of sleep observed in the present cases, especially the absence of or disturbed REM sleep, is inferred to be related to the hypocalcemia."}
{"id": "PMID:220059", "title": "Involvement of pre- and postsynaptic receptors in catecholaminergic control of paradoxical sleep in man.", "content": "In an attempt to clarify the roles of pre- and postsynaptic catecholaminergic (CA) receptors in the regulation of paradoxical sleep (PS) in man, the effects of various doses of chlorpromazine (CPZ) and clonidine (CLN) have been investigated. The action of CPZ was biphasic, small doses enhancing and larger doses depressing the production of PS. However, the effect of CLN was monophasic, showing no modification after small doses, and a decrease in production of PS after moderate doses. In addition, a small dose of CLN, ineffective by itself, completely abolished the effect of a small dose of CPZ. These observations can be explained by preferential blockade of presynaptic alpha-receptors by a small dose of CPZ. They show, too, that it is possible to investigate in man the functional consequences of pharmacological manipulation of pre-synaptic receptors on cerebral CA neurons.", "contents": "Involvement of pre- and postsynaptic receptors in catecholaminergic control of paradoxical sleep in man. In an attempt to clarify the roles of pre- and postsynaptic catecholaminergic (CA) receptors in the regulation of paradoxical sleep (PS) in man, the effects of various doses of chlorpromazine (CPZ) and clonidine (CLN) have been investigated. The action of CPZ was biphasic, small doses enhancing and larger doses depressing the production of PS. However, the effect of CLN was monophasic, showing no modification after small doses, and a decrease in production of PS after moderate doses. In addition, a small dose of CLN, ineffective by itself, completely abolished the effect of a small dose of CPZ. These observations can be explained by preferential blockade of presynaptic alpha-receptors by a small dose of CPZ. They show, too, that it is possible to investigate in man the functional consequences of pharmacological manipulation of pre-synaptic receptors on cerebral CA neurons."}
{"id": "PMID:220062", "title": "Opiate receptor binding affected differentially by opiates and opioid peptides.", "content": "The potencies of various opiates in displacing several 3H-opiate ligands' binding to rat membranes vary depending on the nature of the ligand. Whereas opiate antagonists, as well as the opioid peptides and some agonists (etorphine, levorphanol and phenazocine) display similar affinities in displacing either 3H-opiate or 3H-methionine enkephalin binding, other agonists (such as morphine and oxymorphone) are considerably (20-50 times) weaker in displacing 3H-enkephalin than 3H-dihydromorphine binding. These agonists also compete for 3H-enkephalin binding with shallow displacement curves, and are greatly weakened in displacing 3H-naloxone binding in the presence of sodium. These agonists differ from the other opiate classes by possessing a relatively hydrophilic component in their C-ring moieties which may provide a basis for the differential interactions of drugs with the opiate receptor.", "contents": "Opiate receptor binding affected differentially by opiates and opioid peptides. The potencies of various opiates in displacing several 3H-opiate ligands' binding to rat membranes vary depending on the nature of the ligand. Whereas opiate antagonists, as well as the opioid peptides and some agonists (etorphine, levorphanol and phenazocine) display similar affinities in displacing either 3H-opiate or 3H-methionine enkephalin binding, other agonists (such as morphine and oxymorphone) are considerably (20-50 times) weaker in displacing 3H-enkephalin than 3H-dihydromorphine binding. These agonists also compete for 3H-enkephalin binding with shallow displacement curves, and are greatly weakened in displacing 3H-naloxone binding in the presence of sodium. These agonists differ from the other opiate classes by possessing a relatively hydrophilic component in their C-ring moieties which may provide a basis for the differential interactions of drugs with the opiate receptor."}
{"id": "PMID:220063", "title": "Neurotensin: contractile activity, specific binding, and lack of effect on cyclic nucleotides in intestinal smooth muscle.", "content": "Nuerotensin contracted the isolated longitudinal smooth muscle strip of the guinea-pig intestine. It induced a biphasic response (relaxation followed by contraction) when the muscle was contracted by histamine. Tetrodotoxin blocked the contraction and the contraction phase of the biphasic response. Dose responses of the relaxing effect of neurotensin and its analogs D-Arg8-neurotensin and D-Arg 9-neurotensin on tetrodotoxin-treated muscle gave EC50 values of 5 nM, 5.5 nM and 110 nM for the three peptides, respectively. [3H]Neurotensin bound specifically to membranes prepared from isolated longitudinal muscle strips of the guinea-pig intestine. In binding studies using [3H]neurotensin and unlabelled peptides, the KDs of neurotensin, D-Arg 8-neurotensin and D-Arg9 neurotensin were 4 nM, 2 nM and 300 nM, respectively, values which are in close agreement with the EC50 of the three peptides. Neurotensin had no effect on the cAMP and cGMP contents in longitudinal intestinal muscle strips of the guinea pig, an observation which suggests that cyclic nucleotides are not involved in the mechanism of action of neurotensin in this muscle preparation.", "contents": "Neurotensin: contractile activity, specific binding, and lack of effect on cyclic nucleotides in intestinal smooth muscle. Nuerotensin contracted the isolated longitudinal smooth muscle strip of the guinea-pig intestine. It induced a biphasic response (relaxation followed by contraction) when the muscle was contracted by histamine. Tetrodotoxin blocked the contraction and the contraction phase of the biphasic response. Dose responses of the relaxing effect of neurotensin and its analogs D-Arg8-neurotensin and D-Arg 9-neurotensin on tetrodotoxin-treated muscle gave EC50 values of 5 nM, 5.5 nM and 110 nM for the three peptides, respectively. [3H]Neurotensin bound specifically to membranes prepared from isolated longitudinal muscle strips of the guinea-pig intestine. In binding studies using [3H]neurotensin and unlabelled peptides, the KDs of neurotensin, D-Arg 8-neurotensin and D-Arg9 neurotensin were 4 nM, 2 nM and 300 nM, respectively, values which are in close agreement with the EC50 of the three peptides. Neurotensin had no effect on the cAMP and cGMP contents in longitudinal intestinal muscle strips of the guinea pig, an observation which suggests that cyclic nucleotides are not involved in the mechanism of action of neurotensin in this muscle preparation."}
{"id": "PMID:220070", "title": "Classification of cat retinal ganglion cells into X- and Y-cells with a contrast reversal stimulus.", "content": "A contrast reversal (alternating phase) stimulus was used to study the responses of 150 retinal ganglion cells from 15 adult cats. Because the majority of the cells did not show perfect linear spatial summation, a ratio of the firing rates at two time periods was used to express the degree of nonlinearity. Y-cells showed a high degree of nonlinearity, and their mean null ratio was significantly lower than that of X-cells. With the stimulus at the null position, X-cells had an unmodulated discharge rate which was significantly higher than maintained activity, while the firing rate of Y-cells was lower than maintained activity. With the stimulus placed at an eccentric position in the receptive field, X-cells responded in a sustained manner, while Y-cells respond transiently. Because of these observations, we conclude that X-cells correspond to the sustained cells, while Y-cells correspond to the transient cells.", "contents": "Classification of cat retinal ganglion cells into X- and Y-cells with a contrast reversal stimulus. A contrast reversal (alternating phase) stimulus was used to study the responses of 150 retinal ganglion cells from 15 adult cats. Because the majority of the cells did not show perfect linear spatial summation, a ratio of the firing rates at two time periods was used to express the degree of nonlinearity. Y-cells showed a high degree of nonlinearity, and their mean null ratio was significantly lower than that of X-cells. With the stimulus at the null position, X-cells had an unmodulated discharge rate which was significantly higher than maintained activity, while the firing rate of Y-cells was lower than maintained activity. With the stimulus placed at an eccentric position in the receptive field, X-cells responded in a sustained manner, while Y-cells respond transiently. Because of these observations, we conclude that X-cells correspond to the sustained cells, while Y-cells correspond to the transient cells."}
{"id": "PMID:220071", "title": "Transynaptic transport of procion yellow in the central nervous system.", "content": "Intracellular recordings were performed in slices of the lateral geniculate body, the visual cortex, and the hippocampus of guinea pigs. After recording, Procion Yellow was iontophoretically injected. During the injection period the neurones were activated antidromically and/or transynaptically. Up to 6 h after dye injection slices were fixed in a buffered formaldehyde/sucrose solution and later histologically processed. In the lateral geniculate body, after orthodromic stimulation across the optic tract, optic tract fibers were stained secondarily. Orthodromic activation across intrageniculate connections led to secondarily stained geniculate neurones. In the visual cortex orthodromic activation of the injected neurones across white matter led to secondarily stained fibres travelling in the direction to the white matter or to secondarily stained neurones in the vicinity of the injected neurone. In the hippocampus anti- and orthodromic activation across the alveus or the mossy fibre pathway led to a secondary staining of neighbouring pyramidal neurones and to a secondary staining of fibres which where afferent to the injected neurone. All slices where Procion Yellow was detected in the extracellular space were rejected. These findings led to the conclusion that Procion Yellow must have been transported across chemical synapses from the post- to the presynaptic side. The transport occurred only if the concerned synapses were activated.", "contents": "Transynaptic transport of procion yellow in the central nervous system. Intracellular recordings were performed in slices of the lateral geniculate body, the visual cortex, and the hippocampus of guinea pigs. After recording, Procion Yellow was iontophoretically injected. During the injection period the neurones were activated antidromically and/or transynaptically. Up to 6 h after dye injection slices were fixed in a buffered formaldehyde/sucrose solution and later histologically processed. In the lateral geniculate body, after orthodromic stimulation across the optic tract, optic tract fibers were stained secondarily. Orthodromic activation across intrageniculate connections led to secondarily stained geniculate neurones. In the visual cortex orthodromic activation of the injected neurones across white matter led to secondarily stained fibres travelling in the direction to the white matter or to secondarily stained neurones in the vicinity of the injected neurone. In the hippocampus anti- and orthodromic activation across the alveus or the mossy fibre pathway led to a secondary staining of neighbouring pyramidal neurones and to a secondary staining of fibres which where afferent to the injected neurone. All slices where Procion Yellow was detected in the extracellular space were rejected. These findings led to the conclusion that Procion Yellow must have been transported across chemical synapses from the post- to the presynaptic side. The transport occurred only if the concerned synapses were activated."}
{"id": "PMID:220079", "title": "Alterations of beta-adrenoceptor-density and cAMP-synthesis in rat-erythrocytes after stress erythropoiesis.", "content": "During the maturation of red blood cells from rats after stress erythropoiesis, adenyl cyclase activity and beta-adrenoceptor density (pmoles/mg protein) decrease at distinctly different rates suggesting a different turnover of these membrane units.", "contents": "Alterations of beta-adrenoceptor-density and cAMP-synthesis in rat-erythrocytes after stress erythropoiesis. During the maturation of red blood cells from rats after stress erythropoiesis, adenyl cyclase activity and beta-adrenoceptor density (pmoles/mg protein) decrease at distinctly different rates suggesting a different turnover of these membrane units."}
{"id": "PMID:220080", "title": "[Behaviour of the prolyl hydroxylase to collagen synthesis in KB cells].", "content": "KB cells, which synthetized collagen at a low rate, shown a prolyl hydroxylase activity at the same rate that fibroblast. The relationship between collagen synthesis and prolyl hydroxylase activity in these cells was discussed.", "contents": "[Behaviour of the prolyl hydroxylase to collagen synthesis in KB cells]. KB cells, which synthetized collagen at a low rate, shown a prolyl hydroxylase activity at the same rate that fibroblast. The relationship between collagen synthesis and prolyl hydroxylase activity in these cells was discussed."}
{"id": "PMID:220081", "title": "The detection of superoxide anion from the reaction of oxyhemoglobin and phenylhydrazine using EPR spectroscopy.", "content": "The low temperature EPR spectrum of a quickly reacted mixture of oxyhemoglobin and phenylhydrazine was studied. With the use of a computer, the spectral contribution of methemoglobin in the region of g = 2 was  subtracted. The remaining spectrum was that of an axial free radical (g perpendicular = 2.00, g parallel = 2.06) having the magnetic parameters of superoxide anion. In the presence of superoxide dismutase, this axial radical was not seen, confirming that superoxide anion is indeed generated by the reaction.", "contents": "The detection of superoxide anion from the reaction of oxyhemoglobin and phenylhydrazine using EPR spectroscopy. The low temperature EPR spectrum of a quickly reacted mixture of oxyhemoglobin and phenylhydrazine was studied. With the use of a computer, the spectral contribution of methemoglobin in the region of g = 2 was  subtracted. The remaining spectrum was that of an axial free radical (g perpendicular = 2.00, g parallel = 2.06) having the magnetic parameters of superoxide anion. In the presence of superoxide dismutase, this axial radical was not seen, confirming that superoxide anion is indeed generated by the reaction."}
{"id": "PMID:220082", "title": "[Effect of large doses of phenamine after previous administration of 5-hydroxytryptophan and para-chlorophenylalanine on the spontaneous behavior of cats and the effects induced by caudate nucleus stimulation].", "content": "In non-immobilized male cats the stereotypy behavior evoked by threshold doses of phenamine was registered cyclographically along with the motion arrest reaction, circular reaction and their electrographic \"adjuncts\" (cortical caudate-induced spindles and desynchronization). Against the background of 5-Hydroxytryptophan (5-HT), a serotonine precursor, and p-chlorphenylalanine (PCPA), an inhibitor of the mediator synthesis, phenamine produced stereotype in the formerly administered dose, but its picture changed. Under the effect of 5-HT the amplitude of the stereotypy movements declined, they would become better organized, whereas after administration of PCPA they would, on the contrary, assume a chaotic \"unshackled\" character. The ability of phenamine to upset the behavioral and electrographic characteristics of the caudate nucleus activity was somewhat attenuated by 5-HT and potentiated by PCPA. It is suggested that the release of serotonin in the ventral region of the caudate nucleus intensified by phenamine may be responsible for the limitation of the amplitude and regulating the nature of the stereotype movements evoked by it.", "contents": "[Effect of large doses of phenamine after previous administration of 5-hydroxytryptophan and para-chlorophenylalanine on the spontaneous behavior of cats and the effects induced by caudate nucleus stimulation]. In non-immobilized male cats the stereotypy behavior evoked by threshold doses of phenamine was registered cyclographically along with the motion arrest reaction, circular reaction and their electrographic \"adjuncts\" (cortical caudate-induced spindles and desynchronization). Against the background of 5-Hydroxytryptophan (5-HT), a serotonine precursor, and p-chlorphenylalanine (PCPA), an inhibitor of the mediator synthesis, phenamine produced stereotype in the formerly administered dose, but its picture changed. Under the effect of 5-HT the amplitude of the stereotypy movements declined, they would become better organized, whereas after administration of PCPA they would, on the contrary, assume a chaotic \"unshackled\" character. The ability of phenamine to upset the behavioral and electrographic characteristics of the caudate nucleus activity was somewhat attenuated by 5-HT and potentiated by PCPA. It is suggested that the release of serotonin in the ventral region of the caudate nucleus intensified by phenamine may be responsible for the limitation of the amplitude and regulating the nature of the stereotype movements evoked by it."}
{"id": "PMID:220096", "title": "Diet, central nervous system, and aging.", "content": "A variety of morphological, structural, and chemical changes have been described in the central nervous systems of aging humans and animals. Brain size and volume decline during senescence, and the brain atrophy is accompanied by changes in the number, size, and ultrastructural characteristics of nerve and glial cells. Moreover, recent evidence suggests that the ability of central nervous system cells to communicate with one another via the release of neurotransmitter compounds might be impaired in the elderly. Nutritional factors may play important roles in the aging process of the central nervous system by influencing brain neurotransmission, or by accelerating or retarding geriatric changes in central nervous system structure.", "contents": "Diet, central nervous system, and aging. A variety of morphological, structural, and chemical changes have been described in the central nervous systems of aging humans and animals. Brain size and volume decline during senescence, and the brain atrophy is accompanied by changes in the number, size, and ultrastructural characteristics of nerve and glial cells. Moreover, recent evidence suggests that the ability of central nervous system cells to communicate with one another via the release of neurotransmitter compounds might be impaired in the elderly. Nutritional factors may play important roles in the aging process of the central nervous system by influencing brain neurotransmission, or by accelerating or retarding geriatric changes in central nervous system structure."}
{"id": "PMID:220098", "title": "Prolactin receptors in the ovary.", "content": "The binding of prolactin (PRL) to the plasma membranes of bovine and human ovaries was investigated using both homologous and heterologous 125I-prolactin. Saturation and Scatchard analysis demonstrated that human prolactin binds to human ovarian membranes with a Kd of 2 x 10(-10) M; to bovine ovarian membranes with a Kd of 1.9 x 10(-10) M; and to bovine corpora lutea membranes with a Kd of 1.9 x 10(-10) M. The concentrations of binding sites in bovine and human ovaries were 2.9 x 10(-15) moles/mg of protein and 2.0 x 10(-15) moles/mg of protein, respectively. The number of bindings sites in the bovine corpora lutea was 1.5 x 15(-15) moles/mg of protein. Specificity studies with bovine PRL, ovine PRL, human luteinizing hormone, human follicle-stimulating hormone, and bovine growth hormone showed this binding to be specific. Comparison of binding of PRL to membranes of other target and nontarget tissues suggests that the ovary is one of the primary target tissues. These data suggest that prolactin plays a role in the ovarian cycle.", "contents": "Prolactin receptors in the ovary. The binding of prolactin (PRL) to the plasma membranes of bovine and human ovaries was investigated using both homologous and heterologous 125I-prolactin. Saturation and Scatchard analysis demonstrated that human prolactin binds to human ovarian membranes with a Kd of 2 x 10(-10) M; to bovine ovarian membranes with a Kd of 1.9 x 10(-10) M; and to bovine corpora lutea membranes with a Kd of 1.9 x 10(-10) M. The concentrations of binding sites in bovine and human ovaries were 2.9 x 10(-15) moles/mg of protein and 2.0 x 10(-15) moles/mg of protein, respectively. The number of bindings sites in the bovine corpora lutea was 1.5 x 15(-15) moles/mg of protein. Specificity studies with bovine PRL, ovine PRL, human luteinizing hormone, human follicle-stimulating hormone, and bovine growth hormone showed this binding to be specific. Comparison of binding of PRL to membranes of other target and nontarget tissues suggests that the ovary is one of the primary target tissues. These data suggest that prolactin plays a role in the ovarian cycle."}
{"id": "PMID:220101", "title": "[Denaturation changes in the proteins of the membrane structures of the brain during deprivation of the paradoxical stage of sleep].", "content": "24--96-hour REM-sleep deprivation entailed a rise of SH-group content in the proteins of the rat diencephalon and mesencephalon tissue homogenates, whereas SH-group content of the homogenates of the cortex, pons with medulla oblongata, and cerebellum remained unchanged. Neither did the content of SH-groups change in the soluble protein fraction nor the content of low-molecular thiol substances in the brain parts under study. From among the subcellular fractions of the brain-stem homogenate, the increase of SH-group content after 24-hour REM-sleep deprivation occurred in the synaptosomal and nuclear fractions but not in the mitochondrial one. The REM-sleep deprivation did not affect the --S--S-group content in these fractions. In the anterior parts of the brain-stem only REM-sleep deprivation led to conformational changes of structural proteins towards their denaturation but without rupture of the disulfide bonds.", "contents": "[Denaturation changes in the proteins of the membrane structures of the brain during deprivation of the paradoxical stage of sleep]. 24--96-hour REM-sleep deprivation entailed a rise of SH-group content in the proteins of the rat diencephalon and mesencephalon tissue homogenates, whereas SH-group content of the homogenates of the cortex, pons with medulla oblongata, and cerebellum remained unchanged. Neither did the content of SH-groups change in the soluble protein fraction nor the content of low-molecular thiol substances in the brain parts under study. From among the subcellular fractions of the brain-stem homogenate, the increase of SH-group content after 24-hour REM-sleep deprivation occurred in the synaptosomal and nuclear fractions but not in the mitochondrial one. The REM-sleep deprivation did not affect the --S--S-group content in these fractions. In the anterior parts of the brain-stem only REM-sleep deprivation led to conformational changes of structural proteins towards their denaturation but without rupture of the disulfide bonds."}
{"id": "PMID:220102", "title": "[Effect of blockade of the adrenergic structures of the hypothalamus on thermoregulatory reactions].", "content": "The blockade of alpha-adrenergic receptors of medial preoptic area detained the appearance of vascular thermoregulatory reaction and increased the threshold of the organism central temperature. The blockade of beta-adrenergic structures induced opposite effects. The excitatory efferent impulses from the thermosensitive neurons of the hypothalamus to thermogenic effectors and to the vasomotor system seem to be realized through the alpha-adrenergic structures of the brain, and the inhibitory--through the beta-adrenergic structures.", "contents": "[Effect of blockade of the adrenergic structures of the hypothalamus on thermoregulatory reactions]. The blockade of alpha-adrenergic receptors of medial preoptic area detained the appearance of vascular thermoregulatory reaction and increased the threshold of the organism central temperature. The blockade of beta-adrenergic structures induced opposite effects. The excitatory efferent impulses from the thermosensitive neurons of the hypothalamus to thermogenic effectors and to the vasomotor system seem to be realized through the alpha-adrenergic structures of the brain, and the inhibitory--through the beta-adrenergic structures."}
{"id": "PMID:220103", "title": "[Changes in muscular thermogenesis in cold adapted rats following beta-adrenoreceptor blockade].", "content": "The administration of beta-adrenergic blocking agent propranolol to cold adapted rats entailed some decrease of the total metabolic reaction and body temperature as well as an additive (compensatory) increase of electrical muscle activity. The compensatory effect was more obvious in postural-tonic groups of muscles (m. trapezius, m. masseter) and in deeper portions of muscles (m. tibialis ant., m. trapezius), mainly presented by the red fibers. An adaptive increase of non-shivering thermogenesis and temperature effect of muscular contraction seem to be mainly controlled by beta-adrenergic mechanisms.", "contents": "[Changes in muscular thermogenesis in cold adapted rats following beta-adrenoreceptor blockade]. The administration of beta-adrenergic blocking agent propranolol to cold adapted rats entailed some decrease of the total metabolic reaction and body temperature as well as an additive (compensatory) increase of electrical muscle activity. The compensatory effect was more obvious in postural-tonic groups of muscles (m. trapezius, m. masseter) and in deeper portions of muscles (m. tibialis ant., m. trapezius), mainly presented by the red fibers. An adaptive increase of non-shivering thermogenesis and temperature effect of muscular contraction seem to be mainly controlled by beta-adrenergic mechanisms."}
{"id": "PMID:220105", "title": "[Fabry disease: clinical, biochemical and electron microscopical studies (author's transl)].", "content": "Biochemical investigations on blood-plasma and serum as well as well as electron microscopic investigations on skin lesions biopsy specimens were carried out in one case of morbus Fabry 35 years of age distinctly showing cardio-renal symptoms. The diagnosis of Fabry disease was made when the patient was hospitalized for treatment of a chronic glomerulonephritis. The patients' serum alpha-galactosidase activity was reported to be 10 to 13% of normal controls, whereas the values of trihexosyl-ceramids for blood-plasma and serum were increased. Electron microscopic studies revealed that the endothelial cells and pericytes of the cutaneous vessels as well as the fibroblasts contain numerous liposome-like cytoplasmic inclusions of different size showing an internal lamellar structure with exact periodizity of 65 A. These inclusion are not surrounded by a membrane structure, however, it is possible that the arise from defect lysosomes which accumulate trihexosyl-ceramids owing to insufficient of alpha-galactosidase activity.", "contents": "[Fabry disease: clinical, biochemical and electron microscopical studies (author's transl)]. Biochemical investigations on blood-plasma and serum as well as well as electron microscopic investigations on skin lesions biopsy specimens were carried out in one case of morbus Fabry 35 years of age distinctly showing cardio-renal symptoms. The diagnosis of Fabry disease was made when the patient was hospitalized for treatment of a chronic glomerulonephritis. The patients' serum alpha-galactosidase activity was reported to be 10 to 13% of normal controls, whereas the values of trihexosyl-ceramids for blood-plasma and serum were increased. Electron microscopic studies revealed that the endothelial cells and pericytes of the cutaneous vessels as well as the fibroblasts contain numerous liposome-like cytoplasmic inclusions of different size showing an internal lamellar structure with exact periodizity of 65 A. These inclusion are not surrounded by a membrane structure, however, it is possible that the arise from defect lysosomes which accumulate trihexosyl-ceramids owing to insufficient of alpha-galactosidase activity."}
{"id": "PMID:220107", "title": "Twenty-one years of follow-up studies of familial epidermodysplasia verruciformis.", "content": "21 years of follow-up study of a family with epidermodysplasia verruciformis (e.v.) have shown that members of one family can be infected with different human papillomaviruses (HPVs), either HPV 3 or HPV 4, and sometimes with both. The clinical picture resembled disseminated flat warts in cases induced by HPV 3, whereas in those caused by HPV 4 there were flat red or red-brownish plaques and depigmented pityriasis versicolor-like lesions. Malignancies developed only in family members infected with HPV 4, whereas the cases due to HPV 3 ran a more benign and slowly progressive or stationary course. There were also abortive and regressive cases, and the 3 children in whom the wart-like lesions did not recur after removal had an unimpaired cell-mediated immunity (CMI). In all cases of e.v., irrespective of the inducing virus, CMI was low, which seems to be an important factor in the pathogenesis of the disease. Humoral antibodies directed specifically against HPV 3 were present in the majority of the cases, mainly those infected with HPV 3.", "contents": "Twenty-one years of follow-up studies of familial epidermodysplasia verruciformis. 21 years of follow-up study of a family with epidermodysplasia verruciformis (e.v.) have shown that members of one family can be infected with different human papillomaviruses (HPVs), either HPV 3 or HPV 4, and sometimes with both. The clinical picture resembled disseminated flat warts in cases induced by HPV 3, whereas in those caused by HPV 4 there were flat red or red-brownish plaques and depigmented pityriasis versicolor-like lesions. Malignancies developed only in family members infected with HPV 4, whereas the cases due to HPV 3 ran a more benign and slowly progressive or stationary course. There were also abortive and regressive cases, and the 3 children in whom the wart-like lesions did not recur after removal had an unimpaired cell-mediated immunity (CMI). In all cases of e.v., irrespective of the inducing virus, CMI was low, which seems to be an important factor in the pathogenesis of the disease. Humoral antibodies directed specifically against HPV 3 were present in the majority of the cases, mainly those infected with HPV 3."}
{"id": "PMID:220108", "title": "[Xanthogranuloma in adults. Clinico-pathological study of a case].", "content": "The authors report a case of naevoxanthoendothelioma in a 58-year-old woman. 24 cases of naevoxanthoendothelioma in adults have already been reported in the literature. If the age of the patient is considered, nosologic problems may arise, especially with the strictly cutaneous reticulohistiocytosis of Senear and Caro. Biological and ultrastructural features allow the authors to develop some hypotheses about pathogenesis of the disease.", "contents": "[Xanthogranuloma in adults. Clinico-pathological study of a case]. The authors report a case of naevoxanthoendothelioma in a 58-year-old woman. 24 cases of naevoxanthoendothelioma in adults have already been reported in the literature. If the age of the patient is considered, nosologic problems may arise, especially with the strictly cutaneous reticulohistiocytosis of Senear and Caro. Biological and ultrastructural features allow the authors to develop some hypotheses about pathogenesis of the disease."}
{"id": "PMID:220109", "title": "Herpes simplex virus isolation from pyoderma gangrenosum lesions in a patient with chronic lymphatic leukemia.", "content": "Herpes simplex virus type 2 was isolated and identified from the vesicular border of pyoderma gangrenosum lesions on the genital region of a patient with chronic lymphatic leukemia. Dramatic relief of pain as well as quick disappearance of the vesicular margin of the lesions and of the inflammatory halo around them occurred as a result of local treatment with a solution of zinc acetate. A careful search for a viral agent should be done in every case of pyoderma gangrenosum occurring in a patient with a hematological malignancy or/and impaired immunity, especially if the lesions are on the face or in the genital region.", "contents": "Herpes simplex virus isolation from pyoderma gangrenosum lesions in a patient with chronic lymphatic leukemia. Herpes simplex virus type 2 was isolated and identified from the vesicular border of pyoderma gangrenosum lesions on the genital region of a patient with chronic lymphatic leukemia. Dramatic relief of pain as well as quick disappearance of the vesicular margin of the lesions and of the inflammatory halo around them occurred as a result of local treatment with a solution of zinc acetate. A careful search for a viral agent should be done in every case of pyoderma gangrenosum occurring in a patient with a hematological malignancy or/and impaired immunity, especially if the lesions are on the face or in the genital region."}
{"id": "PMID:220119", "title": "Theophylline: biochemical pharmacology and pharmacokinetics.", "content": "Theophylline and its derivatives, such as aminophylline, have an established role as bronchodilators, although their mode of action in man is not clear. There is circumstantial evidence that therapeutic doses of theophylline may have a phosphodiesterase inhibiting effect, thus potentiating the effects of cyclic AMP. However, it remains to be established whether this is the primary mode of action of theophylline at the biochemical level. The pathways of theophylline metabolism have been clarified, although most of the enzymes involved have not been characterized. Hepatic microsomal enzyme induction by polycyclic hydrocarbons will increase the rate of theophylline elimination. There are a number of factors which influence theophylline clearance in adults, which is known to be highly variable. These factors include obesity, smoking habit, diet and the presence of such diseases as hepatic cirrhosis, acute pulmonary oedema, cor pulmonale and viral respiratory infection. There is a good correlation between plasma theophylline level and bronchodilator effect. This can be demonstrated at plasma levels as low as 5 microgram/ml, although optimal levels are usually greater than 10 microgram/ml. Unacceptable toxicity usually occurs in association with plasma levels greater than 20 microgram/ml. The maintenance of adequate plasma theophylline levels by the use of a sustained-release aminophylline tablet is discussed.", "contents": "Theophylline: biochemical pharmacology and pharmacokinetics. Theophylline and its derivatives, such as aminophylline, have an established role as bronchodilators, although their mode of action in man is not clear. There is circumstantial evidence that therapeutic doses of theophylline may have a phosphodiesterase inhibiting effect, thus potentiating the effects of cyclic AMP. However, it remains to be established whether this is the primary mode of action of theophylline at the biochemical level. The pathways of theophylline metabolism have been clarified, although most of the enzymes involved have not been characterized. Hepatic microsomal enzyme induction by polycyclic hydrocarbons will increase the rate of theophylline elimination. There are a number of factors which influence theophylline clearance in adults, which is known to be highly variable. These factors include obesity, smoking habit, diet and the presence of such diseases as hepatic cirrhosis, acute pulmonary oedema, cor pulmonale and viral respiratory infection. There is a good correlation between plasma theophylline level and bronchodilator effect. This can be demonstrated at plasma levels as low as 5 microgram/ml, although optimal levels are usually greater than 10 microgram/ml. Unacceptable toxicity usually occurs in association with plasma levels greater than 20 microgram/ml. The maintenance of adequate plasma theophylline levels by the use of a sustained-release aminophylline tablet is discussed."}
{"id": "PMID:220123", "title": "Failure of severe maternal stress or ACTH during pregnancy to affect emotionality of male rat offspring: implications of litter effects for prenatal studies.", "content": "Daily maternal neck restraint, whole body restraint, hyperthermia, and ACTH treatment during the last 3rd of gestation had no reliable effect on open-field and cage-emergence behavior in male Sprague-Dawley offspring. Many of these treatments, however, produced considerable maternal pathology and evidence for maternal adrenocorticoid release. Significant litter effects were found for almost every morphological and behavioral measure. Failure to control for the litter variable may account for many previously reported effects of prenatal stress on emotionality in rats. Female rats showed greater activity and less defecation than males on postpubertal open-field and cage emergence tests.", "contents": "Failure of severe maternal stress or ACTH during pregnancy to affect emotionality of male rat offspring: implications of litter effects for prenatal studies. Daily maternal neck restraint, whole body restraint, hyperthermia, and ACTH treatment during the last 3rd of gestation had no reliable effect on open-field and cage-emergence behavior in male Sprague-Dawley offspring. Many of these treatments, however, produced considerable maternal pathology and evidence for maternal adrenocorticoid release. Significant litter effects were found for almost every morphological and behavioral measure. Failure to control for the litter variable may account for many previously reported effects of prenatal stress on emotionality in rats. Female rats showed greater activity and less defecation than males on postpubertal open-field and cage emergence tests."}
{"id": "PMID:220127", "title": "Insulin receptors in AH-66 ascites hepatoma cells and liver of tumor-bearing rats.", "content": "Properties of insulin receptor on plasma membranes isolated from AH-66 ascites hepatoma cells and liver of tumor-bearing rats were studied. Specific binding (total binding minus nonspecific binding) of 125-I-labeled insulin to plasma membranes from AH-66 tumor cells and liver of normal and tumor-bearing rats were 33, 31, and 16% of a fixed amount of labeled insulin (1 x 10(5) cpm) added to each membrane preparation, respectively. Using Nisonoff plot, these membranes were found to possess at least two types of insulin receptors with a high affinity-low capacity and a low affinity-high capacity, as has been shown in normal liver. Total number of binding sites (high affinity plus low affinity sites, 8.4 x 10(-12) mol/mg protein) in hepatoma cells was more than that (7.0 x 10(-12) mol/mg protein) in normal rat liver. However, kinetic constants of binding in receptors of two types on tumor cells and tumor-bearing rat liver were similar to those of membrane receptors from normal rat liver. Insulin receptors of the hepatoma cells were considered to be highly specific for insulin from the results of competition with other peptide hormones. Inhibition of insulin binding with the tumor cell membranes by concanavalin-A, a competitive inhibitor for insulin receptor sites, did not differ very greatly from that of normal liver.", "contents": "Insulin receptors in AH-66 ascites hepatoma cells and liver of tumor-bearing rats. Properties of insulin receptor on plasma membranes isolated from AH-66 ascites hepatoma cells and liver of tumor-bearing rats were studied. Specific binding (total binding minus nonspecific binding) of 125-I-labeled insulin to plasma membranes from AH-66 tumor cells and liver of normal and tumor-bearing rats were 33, 31, and 16% of a fixed amount of labeled insulin (1 x 10(5) cpm) added to each membrane preparation, respectively. Using Nisonoff plot, these membranes were found to possess at least two types of insulin receptors with a high affinity-low capacity and a low affinity-high capacity, as has been shown in normal liver. Total number of binding sites (high affinity plus low affinity sites, 8.4 x 10(-12) mol/mg protein) in hepatoma cells was more than that (7.0 x 10(-12) mol/mg protein) in normal rat liver. However, kinetic constants of binding in receptors of two types on tumor cells and tumor-bearing rat liver were similar to those of membrane receptors from normal rat liver. Insulin receptors of the hepatoma cells were considered to be highly specific for insulin from the results of competition with other peptide hormones. Inhibition of insulin binding with the tumor cell membranes by concanavalin-A, a competitive inhibitor for insulin receptor sites, did not differ very greatly from that of normal liver."}
{"id": "PMID:220128", "title": "Isolation of a sarcoma virus from a spontaneous chicken tumor.", "content": "A spontaneous tumor was obtained from a hen of White-Leghorn stock raised in a local farm in Yamaguchi City, in December 1973. The tumor had characteristics of fibro- or myxofibro-sarcoma and could be maintained by transplantation in chickens of similar flocks. This tumor was proved to produce sarcoma virus at 33rd passage and the transforming virus was designated as Y73 sarcoma virus. Biological studies suggested that the virus recovered from the tumor belonged to avian leukosis-sarcoma complex having subgroup A specificity. The possibility of defectiveness of this virus will be discussed.", "contents": "Isolation of a sarcoma virus from a spontaneous chicken tumor. A spontaneous tumor was obtained from a hen of White-Leghorn stock raised in a local farm in Yamaguchi City, in December 1973. The tumor had characteristics of fibro- or myxofibro-sarcoma and could be maintained by transplantation in chickens of similar flocks. This tumor was proved to produce sarcoma virus at 33rd passage and the transforming virus was designated as Y73 sarcoma virus. Biological studies suggested that the virus recovered from the tumor belonged to avian leukosis-sarcoma complex having subgroup A specificity. The possibility of defectiveness of this virus will be discussed."}
{"id": "PMID:220130", "title": "Effects of alcohols on the actions of VIP and secretin on acinar cells from guinea pig pancreas.", "content": "In dispersed acini prepared from guinea pig pancreas, ethanol inhibited the increase in amylase secretion caused by cholecystokinin, carbachol, secretin, or vasoactive intestinal peptide. Ethanol did not alter binding of [125I] vasoactive intestinal peptide to pancreatic acinar cells or the inhibition of binding cause by secretin or vasoactive intestinal peptide. Ethanol potentiated the increase in adenylate cyclase activity and cellular adenosine 3':5'-monophosphate caused by secretin or vasoactive intestinal peptide. This potentiating action was reversible and could also be detected with straight-chain alcohols having fewer than seven carbon atoms. At sufficiently high concentrations, straight-chain alcohols having more than two carbon atoms inhibited the action of secretin or vasoactive intestinal peptide on adenylate cyclase activity, and this and this action was irreversible.", "contents": "Effects of alcohols on the actions of VIP and secretin on acinar cells from guinea pig pancreas. In dispersed acini prepared from guinea pig pancreas, ethanol inhibited the increase in amylase secretion caused by cholecystokinin, carbachol, secretin, or vasoactive intestinal peptide. Ethanol did not alter binding of [125I] vasoactive intestinal peptide to pancreatic acinar cells or the inhibition of binding cause by secretin or vasoactive intestinal peptide. Ethanol potentiated the increase in adenylate cyclase activity and cellular adenosine 3':5'-monophosphate caused by secretin or vasoactive intestinal peptide. This potentiating action was reversible and could also be detected with straight-chain alcohols having fewer than seven carbon atoms. At sufficiently high concentrations, straight-chain alcohols having more than two carbon atoms inhibited the action of secretin or vasoactive intestinal peptide on adenylate cyclase activity, and this and this action was irreversible."}
{"id": "PMID:220132", "title": "The ultrastructural localization of transport ATPase in the rat liver at non-bile canalicular plasma membranes.", "content": "Na,K-ATPase in rat livers was localized cytochemically at the ultrastructural level. The Ernst technique, a method using p-nitrophenylphosphate (pNPP) substrate, was used to demonstrate ouabain-sensitive, K-dependent phosphatase, an enzyme of the Na,K-ATPase reaction sequence. Reaction product was localized predominantly on the sinusoidal and non-bile canalicular (intercellular) surfaces. This localization contrasts with previous histo-chemical studies using ATP substrate and with models that have considered the transport enzyme to be localized at the canalicular surface. If Na,K-ATPase is of importance in bile salt independent flow, a significant presence of the enzyme at sites other than the canalicular membrane suggests that a paracellular movement of sodium and water into the canaliculus must be considered.", "contents": "The ultrastructural localization of transport ATPase in the rat liver at non-bile canalicular plasma membranes. Na,K-ATPase in rat livers was localized cytochemically at the ultrastructural level. The Ernst technique, a method using p-nitrophenylphosphate (pNPP) substrate, was used to demonstrate ouabain-sensitive, K-dependent phosphatase, an enzyme of the Na,K-ATPase reaction sequence. Reaction product was localized predominantly on the sinusoidal and non-bile canalicular (intercellular) surfaces. This localization contrasts with previous histo-chemical studies using ATP substrate and with models that have considered the transport enzyme to be localized at the canalicular surface. If Na,K-ATPase is of importance in bile salt independent flow, a significant presence of the enzyme at sites other than the canalicular membrane suggests that a paracellular movement of sodium and water into the canaliculus must be considered."}
{"id": "PMID:220148", "title": "Hepatocellular carcinoma in primary biliary cirrhosis: report of four cases.", "content": "Of 98 patients dying with primary biliary cirrhosis only four developed hepatocellular carcinoma. It is suggested that the development of hepatocellular carcinoma is uncommon in this type of chronic liver disease because of its known female preponderance, and the fact that cirrhosis develops late in the course of the illness.", "contents": "Hepatocellular carcinoma in primary biliary cirrhosis: report of four cases. Of 98 patients dying with primary biliary cirrhosis only four developed hepatocellular carcinoma. It is suggested that the development of hepatocellular carcinoma is uncommon in this type of chronic liver disease because of its known female preponderance, and the fact that cirrhosis develops late in the course of the illness."}
{"id": "PMID:220157", "title": "Histochemistry and cytochemistry of 3,3'-diaminobenzidine. A review.", "content": "The review presents applications of 3,3'-diaminobenzidine (DAB) to histochemistry and cytochemistry, including demonstration of oxidative enzymes and hemoproteins, tracer experiments, immunocytochemistry and methods based on non-enzymic DAB oxidation. A special attention is paid to methodological problems concerning the specifity and sensitivity of DAB reactions.", "contents": "Histochemistry and cytochemistry of 3,3'-diaminobenzidine. A review. The review presents applications of 3,3'-diaminobenzidine (DAB) to histochemistry and cytochemistry, including demonstration of oxidative enzymes and hemoproteins, tracer experiments, immunocytochemistry and methods based on non-enzymic DAB oxidation. A special attention is paid to methodological problems concerning the specifity and sensitivity of DAB reactions."}
{"id": "PMID:220158", "title": "Studies on the physiology of pollen and pollen tube growth. IV Eschscholtzia californica Cham.", "content": "Eschscholtzia californica stigmas with germinating pollen at different stages of development were the subject of histochemical studies which aimed the localization of several enzymes like phosphorylase, leucine amino peptidase, nonspecific esterase, cytochrome oxidase, aldolase, alpha-glycerophosphate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, monoamine oxidase, alpha-galactosidase, beta-glucosidase and beta-galactosidase. Pollen and pollen tubes were shown to contain starch, lipid, proteins and soluble sugars as the storage products. These storage products were utilized during germination and tube growth. The role of different enzymes in the process of germination and tube growth is discussed. From the distribution of oxidoreductases it is inferred that respiration plays an essential role in the tube growth. During pollen germination probably the reserve proteins were transported to pollen tube tip. The increase of activity of alpha-and beta-galactosidase in pollen tubes indicates on their involvement in carbohydrate metabolism. The role of alpha-galactosidase in the metabolism of galactolipids is also inferred. Similarly, the reaction catalysed by beta-glucosidase resulted in the production of aglycon and glucose; of these the former possibly act as a substrate of peroxidase. Some of the glycosidases diffused out of pollen wall on the stigma and participated in the release of free sugars of the female tissue.", "contents": "Studies on the physiology of pollen and pollen tube growth. IV Eschscholtzia californica Cham. Eschscholtzia californica stigmas with germinating pollen at different stages of development were the subject of histochemical studies which aimed the localization of several enzymes like phosphorylase, leucine amino peptidase, nonspecific esterase, cytochrome oxidase, aldolase, alpha-glycerophosphate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, monoamine oxidase, alpha-galactosidase, beta-glucosidase and beta-galactosidase. Pollen and pollen tubes were shown to contain starch, lipid, proteins and soluble sugars as the storage products. These storage products were utilized during germination and tube growth. The role of different enzymes in the process of germination and tube growth is discussed. From the distribution of oxidoreductases it is inferred that respiration plays an essential role in the tube growth. During pollen germination probably the reserve proteins were transported to pollen tube tip. The increase of activity of alpha-and beta-galactosidase in pollen tubes indicates on their involvement in carbohydrate metabolism. The role of alpha-galactosidase in the metabolism of galactolipids is also inferred. Similarly, the reaction catalysed by beta-glucosidase resulted in the production of aglycon and glucose; of these the former possibly act as a substrate of peroxidase. Some of the glycosidases diffused out of pollen wall on the stigma and participated in the release of free sugars of the female tissue."}
{"id": "PMID:220162", "title": "Clinical studies using radiocolloid in chyluria.", "content": "Very little radioactive colloid, injected subcutaneously is excreted in urine by the normal kidney. In chyluria patients, however, radiocolloid injected subcutaneously (not venously) is passed through in larger quantities in the urine to the control patients, because of the lymphatic communication with urinary tract. As far as we investigated, measurement of the radiocolloid in urine is a valid clinical test for chyluria patients.", "contents": "Clinical studies using radiocolloid in chyluria. Very little radioactive colloid, injected subcutaneously is excreted in urine by the normal kidney. In chyluria patients, however, radiocolloid injected subcutaneously (not venously) is passed through in larger quantities in the urine to the control patients, because of the lymphatic communication with urinary tract. As far as we investigated, measurement of the radiocolloid in urine is a valid clinical test for chyluria patients."}
{"id": "PMID:220163", "title": "Primary liver tumors in the pediatric age group: an angiographic challenge.", "content": "Eleven children, ranging in age from three months to fifteen years, with primary liver tumors were examined by large volume direct magnification arteriography (2.5--3 ml of contrast material per 1 kg body weight for a single selective study). The following tumors were found: hepatoblastoma (1), hepatocellular carcinoma of the adult type, hepatoma (3), infantile hemangioendothelioma (4), hemangiosarcoma (1), focal nodular hyperplasia (1) and cystic mesenchymal hamartoma (1). Some of the tumors have a quite typical angiographic appearance as infantile hemangioendothelioma, hemangiosarcoma, cystic mesenchymal hamartoma. The other highly vascular neoplasms show unspecific signs of vascular malignant tumors; subtile angiographic signs may, however, be present and help in the differential diagnosis.", "contents": "Primary liver tumors in the pediatric age group: an angiographic challenge. Eleven children, ranging in age from three months to fifteen years, with primary liver tumors were examined by large volume direct magnification arteriography (2.5--3 ml of contrast material per 1 kg body weight for a single selective study). The following tumors were found: hepatoblastoma (1), hepatocellular carcinoma of the adult type, hepatoma (3), infantile hemangioendothelioma (4), hemangiosarcoma (1), focal nodular hyperplasia (1) and cystic mesenchymal hamartoma (1). Some of the tumors have a quite typical angiographic appearance as infantile hemangioendothelioma, hemangiosarcoma, cystic mesenchymal hamartoma. The other highly vascular neoplasms show unspecific signs of vascular malignant tumors; subtile angiographic signs may, however, be present and help in the differential diagnosis."}
{"id": "PMID:220165", "title": "Effects of adrenalectomy and hypercorticism on the ACTH content of the anterior and posterior pituitary in rats with inherited diabetes insipidus (Brattleboro strain).", "content": "The effects of adrenalectomy (Adx) and hypercorticism on the ACTH content in the anterior (AH) and the neurointermediate lobe (NIL) of the pituitary in Long Evans (+/+), heterozygous (+/DI) and homozygous (DI/DI) Brattleboro rats were determined using dispersed adrenal cells bioassay. Adx decreased the NIL-ACTH content in +/DI and DI/DI rats and left it unchanged in the +/+ rats. Adx increased the AH-ACTH content in the three groups. Hypercorticism had a delayed decreasing effect both in the AH and in the NIL in all rats, with one exception for the NIL in DI/DI rats. Conversely to what appeared in Wistar rats, in Long Evans and Brattleboro rats the corticosterone administered in drinking water was unable to reduce the increase in AH-ACTH activity. These data suggest that Brattleboro, and, to a lesser extent, Long Evans rats from which the former are derived present some particularities in the regulation of their corticotropic function at the AH and the NIL level. We also observed that NaCl (0.9%) added to drinking water and hypercorticism are two factors able to increase diabetes insipidus in homozygous rats without modifying the water intake in Long Evans and heterozygous rats.", "contents": "Effects of adrenalectomy and hypercorticism on the ACTH content of the anterior and posterior pituitary in rats with inherited diabetes insipidus (Brattleboro strain). The effects of adrenalectomy (Adx) and hypercorticism on the ACTH content in the anterior (AH) and the neurointermediate lobe (NIL) of the pituitary in Long Evans (+/+), heterozygous (+/DI) and homozygous (DI/DI) Brattleboro rats were determined using dispersed adrenal cells bioassay. Adx decreased the NIL-ACTH content in +/DI and DI/DI rats and left it unchanged in the +/+ rats. Adx increased the AH-ACTH content in the three groups. Hypercorticism had a delayed decreasing effect both in the AH and in the NIL in all rats, with one exception for the NIL in DI/DI rats. Conversely to what appeared in Wistar rats, in Long Evans and Brattleboro rats the corticosterone administered in drinking water was unable to reduce the increase in AH-ACTH activity. These data suggest that Brattleboro, and, to a lesser extent, Long Evans rats from which the former are derived present some particularities in the regulation of their corticotropic function at the AH and the NIL level. We also observed that NaCl (0.9%) added to drinking water and hypercorticism are two factors able to increase diabetes insipidus in homozygous rats without modifying the water intake in Long Evans and heterozygous rats."}
{"id": "PMID:220166", "title": "Effect of chlorphentermine on hormone content and function of the adrenal cortex in rats.", "content": "Amphiphilic drugs like chlorphentermine induce a generalized lipid storage disease upon chronic application. The adrenal cortex is among the organs most heavily affected. We therefore determined the urinary corticosterone excretion during the treatment of rats with chlorphentermine and the corticosterone content of the adrenals and its blood level at the end of the treatment period. In addition, the responsiveness of adrenal cortex was tested by application of ACTH. During treatment, the corticosterone excretion declined considerably. Both the corticosterone content of the adrenals and the plasma level were found depressed at the end of a treatment period of 8 weeks. The ACTH evoked response was also diminished. The results indicate that the chlorphentermine-induced lipidosis is associated with a reduced corticosterone production of the adrenal cortex of rats. At present it cannot be decided whether the cortical insufficiency is causally related to lipidotic alterations of the cortical cells, or whether it is caused or additionally influenced by alteration at a higher level, e.g. hypothalamic centers or anterior pituitary.", "contents": "Effect of chlorphentermine on hormone content and function of the adrenal cortex in rats. Amphiphilic drugs like chlorphentermine induce a generalized lipid storage disease upon chronic application. The adrenal cortex is among the organs most heavily affected. We therefore determined the urinary corticosterone excretion during the treatment of rats with chlorphentermine and the corticosterone content of the adrenals and its blood level at the end of the treatment period. In addition, the responsiveness of adrenal cortex was tested by application of ACTH. During treatment, the corticosterone excretion declined considerably. Both the corticosterone content of the adrenals and the plasma level were found depressed at the end of a treatment period of 8 weeks. The ACTH evoked response was also diminished. The results indicate that the chlorphentermine-induced lipidosis is associated with a reduced corticosterone production of the adrenal cortex of rats. At present it cannot be decided whether the cortical insufficiency is causally related to lipidotic alterations of the cortical cells, or whether it is caused or additionally influenced by alteration at a higher level, e.g. hypothalamic centers or anterior pituitary."}
{"id": "PMID:220167", "title": "The carbohydrate moiety of human chorionic gonadotropin: lack of competition with HCG for testicular receptors and anti-HCG-serum.", "content": "A glycopeptide fraction has been prepared from human chorionic gonadotropin (HCG) by digesting the reduced, S-carboxymethylated hormone with pronase and fractionating the digest by gel exclusion chromatography. The glycopeptide fraction was estimated to contain (w/w) 29% sialic acid, 31% hexose, 23% hexosamine, and 17% amino acids and/or peptides; thus, the glycopeptide mixture is 83% carbohydrate compared to intact HCG which is about 30% carbohdyrate. There was no cross-reactivity of the glycopeptide fraction with an antiserum directed against HCG. Also, when corrected for minimal non-specific effects, the fraction failed to displace 125I-HCG from a rat testicular preparation even when tested at a 10,000-fold (w/w) excess. Thus, any model involving carbohydrate effects in gonadotropin action must include the protein moiety as a necessary component.", "contents": "The carbohydrate moiety of human chorionic gonadotropin: lack of competition with HCG for testicular receptors and anti-HCG-serum. A glycopeptide fraction has been prepared from human chorionic gonadotropin (HCG) by digesting the reduced, S-carboxymethylated hormone with pronase and fractionating the digest by gel exclusion chromatography. The glycopeptide fraction was estimated to contain (w/w) 29% sialic acid, 31% hexose, 23% hexosamine, and 17% amino acids and/or peptides; thus, the glycopeptide mixture is 83% carbohydrate compared to intact HCG which is about 30% carbohdyrate. There was no cross-reactivity of the glycopeptide fraction with an antiserum directed against HCG. Also, when corrected for minimal non-specific effects, the fraction failed to displace 125I-HCG from a rat testicular preparation even when tested at a 10,000-fold (w/w) excess. Thus, any model involving carbohydrate effects in gonadotropin action must include the protein moiety as a necessary component."}
{"id": "PMID:220171", "title": "Effect of bromocriptine on the control of plasma aldosterone diurnal variation in normal supine man.", "content": "In order to investigate the role of prolactin in the control of the circadian rhythm of plasma aldosterone (PA), plasma renin activity (PRA), cortisol (PC), aldosterone and prolactin (PRL) levels were determined in samples at 4-hour intervals from 5 normal supine men over a period of 24 h under basal conditions and subsequently over a period of 24 h during suppression of prolactin release by bromocriptine (CB-154). After suppression of prolactin, statistically signific1nt circadian rhythms in PC and PA have been detected with a moderate decrease of PA concentration, while the PC level remained unalterated. PRA rhythmicity persisted with a significant shift of acrophase and remarkable reduction of plasma levels. Moreover, during CB administration a significant correlation was obtained between PA and PC, while no correlation was detected between PA and PRA. These data are consistent with the following concepts: (a) the prolactin does not play a significant role in the regulation of circadian rhythm and concentration of plasma aldosterone in normal supine men, and (b) bromocriptine induces a remarkable reduction of PRA and a variable decrease in plasma aldosterone, but it does not influence the secretion of cortisol in normal subjects.", "contents": "Effect of bromocriptine on the control of plasma aldosterone diurnal variation in normal supine man. In order to investigate the role of prolactin in the control of the circadian rhythm of plasma aldosterone (PA), plasma renin activity (PRA), cortisol (PC), aldosterone and prolactin (PRL) levels were determined in samples at 4-hour intervals from 5 normal supine men over a period of 24 h under basal conditions and subsequently over a period of 24 h during suppression of prolactin release by bromocriptine (CB-154). After suppression of prolactin, statistically signific1nt circadian rhythms in PC and PA have been detected with a moderate decrease of PA concentration, while the PC level remained unalterated. PRA rhythmicity persisted with a significant shift of acrophase and remarkable reduction of plasma levels. Moreover, during CB administration a significant correlation was obtained between PA and PC, while no correlation was detected between PA and PRA. These data are consistent with the following concepts: (a) the prolactin does not play a significant role in the regulation of circadian rhythm and concentration of plasma aldosterone in normal supine men, and (b) bromocriptine induces a remarkable reduction of PRA and a variable decrease in plasma aldosterone, but it does not influence the secretion of cortisol in normal subjects."}
{"id": "PMID:220172", "title": "Interaction of aging with in vitro adrenocortical responsiveness to ACTH and cyclic AMP.", "content": "In vitro adrenal accumulation of cyclic 3'5'-adenosine monophosphate (cyclic AMP) and release of corticosterone in response to adrenocorticotropic hormone (ACTH), cyclic AMP or theophylline was assessed in 60- and 340-day-old male rats. Adrenal tissue from mature animals secreted significantly smaller quantities of corticosterone in response to ACTH, theophylline or cyclic AMP. Additionally, mature tissue accumulated significantly less cyclic AMP after treatment with ACTH or a combination of ACTH and theophylline. The data suggest an age-related refractoriness of adrenal cortical tissue to ACTH which may in part be related to decreased availability of and/or sensitivity to cyclic AMP.", "contents": "Interaction of aging with in vitro adrenocortical responsiveness to ACTH and cyclic AMP. In vitro adrenal accumulation of cyclic 3'5'-adenosine monophosphate (cyclic AMP) and release of corticosterone in response to adrenocorticotropic hormone (ACTH), cyclic AMP or theophylline was assessed in 60- and 340-day-old male rats. Adrenal tissue from mature animals secreted significantly smaller quantities of corticosterone in response to ACTH, theophylline or cyclic AMP. Additionally, mature tissue accumulated significantly less cyclic AMP after treatment with ACTH or a combination of ACTH and theophylline. The data suggest an age-related refractoriness of adrenal cortical tissue to ACTH which may in part be related to decreased availability of and/or sensitivity to cyclic AMP."}
{"id": "PMID:220173", "title": "13C-NMR spectroscopy of human serum high density lipoprotein enriched with labelled phospholipids.", "content": "Native human serum high density lipoprotein (HDL) (d = 1.063--1.21g x cm-3) was enriched with phosphatidylcholines labelled with 13C in the polar head group ([N-13CH3]choline) and in the fatty acyl chains ([26-13C]cholesterol) and its linoleic acid ester using the previously described exchange method (Stoffel et al. 1978). The properties of the HDL particles with the exchanged lipid classes were the same as those of the native particles (Mr, CD, fluorescence, lipid and apoprotein stoichiometry, electrophoretic mobility). The T1-times were very similar to those obtained previously with recombined apolipoprotein-[13C]lipid complexes and further support our proposals concerning lipid and apoprotein interactions in the HDL particle.", "contents": "13C-NMR spectroscopy of human serum high density lipoprotein enriched with labelled phospholipids. Native human serum high density lipoprotein (HDL) (d = 1.063--1.21g x cm-3) was enriched with phosphatidylcholines labelled with 13C in the polar head group ([N-13CH3]choline) and in the fatty acyl chains ([26-13C]cholesterol) and its linoleic acid ester using the previously described exchange method (Stoffel et al. 1978). The properties of the HDL particles with the exchanged lipid classes were the same as those of the native particles (Mr, CD, fluorescence, lipid and apoprotein stoichiometry, electrophoretic mobility). The T1-times were very similar to those obtained previously with recombined apolipoprotein-[13C]lipid complexes and further support our proposals concerning lipid and apoprotein interactions in the HDL particle."}
{"id": "PMID:220174", "title": "Response of platelets exposed to potassium tetraperoxochromate, an extracellular source of singlet oxygen, hydroxyl radicals, superoxide anions and hydrogen-peroxide.", "content": "When potassium tetraperoxochromate (K3CrO8) is added to platelet suspension media it decomposes to the oxygen species hydrogen peroxide, superoxide radicals, hydroxyl radicals, and singlet oxygen. K3CrO8 induces a reversible shape change and aggregation of human platelets and, in the presence of Tris or sucrose, also the release of serotonin. Its effect on shape change and aggregation is due to the long-lived species hydrogen peroxide and is abolished by indomethacin and acetylsalicylic acid. Superoxide radicals, which are formed from K3CrO8 in HEPES-containing media do not evoke a platelet response. The release of serotonin depends on an interaction of hydroxyl radicals with Tris or sucrose and is associated with excessive formation of thiobarbituric acid-reactive material from platelets. Other scavengers of hydroxyl radicals such as mannitol, dimethylsulfoxide, EDTA or histidine prevent the release and the formation of thiobarbituric acid chromogen. Interaction of hydroxyl radicals with Tris or sucrose most likely results in the generation of short-lived intermediates which may act on platelets to produce thiobarbituric acid chromogen and to promote serotonin release. These effects on platelets are not inhibited by acetylsalicylic acid or indomethacin. Therefore the highly reactive hydroxyl radical and singlet oxygen, when generated extracellularly, do not mediate their effects via the enzyme-catalyzed prostaglandin pathway, in contrast to those evoked by the less reactive hydrogen peroxide.", "contents": "Response of platelets exposed to potassium tetraperoxochromate, an extracellular source of singlet oxygen, hydroxyl radicals, superoxide anions and hydrogen-peroxide. When potassium tetraperoxochromate (K3CrO8) is added to platelet suspension media it decomposes to the oxygen species hydrogen peroxide, superoxide radicals, hydroxyl radicals, and singlet oxygen. K3CrO8 induces a reversible shape change and aggregation of human platelets and, in the presence of Tris or sucrose, also the release of serotonin. Its effect on shape change and aggregation is due to the long-lived species hydrogen peroxide and is abolished by indomethacin and acetylsalicylic acid. Superoxide radicals, which are formed from K3CrO8 in HEPES-containing media do not evoke a platelet response. The release of serotonin depends on an interaction of hydroxyl radicals with Tris or sucrose and is associated with excessive formation of thiobarbituric acid-reactive material from platelets. Other scavengers of hydroxyl radicals such as mannitol, dimethylsulfoxide, EDTA or histidine prevent the release and the formation of thiobarbituric acid chromogen. Interaction of hydroxyl radicals with Tris or sucrose most likely results in the generation of short-lived intermediates which may act on platelets to produce thiobarbituric acid chromogen and to promote serotonin release. These effects on platelets are not inhibited by acetylsalicylic acid or indomethacin. Therefore the highly reactive hydroxyl radical and singlet oxygen, when generated extracellularly, do not mediate their effects via the enzyme-catalyzed prostaglandin pathway, in contrast to those evoked by the less reactive hydrogen peroxide."}
{"id": "PMID:220175", "title": "Studies on cytochrome c oxidase, IV[1--3]. Primary structure and function of subunit II.", "content": "The amino acid sequence of polypeptide II from beef heart cytochrome c oxidase is described. Comparision of this primary structure with those of azurins, plastocyanins and stellacyanins reveals clear homologies among them. Thus subunit II of the oxidase is a member of this copper protein family. The sequence homology indicates a copper binding site consisting of two invariant histidines and two sulfur-containing amino acids. Thus subunit II is like a blue copper protein with type I copper.", "contents": "Studies on cytochrome c oxidase, IV[1--3]. Primary structure and function of subunit II. The amino acid sequence of polypeptide II from beef heart cytochrome c oxidase is described. Comparision of this primary structure with those of azurins, plastocyanins and stellacyanins reveals clear homologies among them. Thus subunit II of the oxidase is a member of this copper protein family. The sequence homology indicates a copper binding site consisting of two invariant histidines and two sulfur-containing amino acids. Thus subunit II is like a blue copper protein with type I copper."}
{"id": "PMID:220176", "title": "Sphingomyelinase activities in cultured skin fibroblasts from patients with Niemann-Pick Disease.", "content": "Sphingomyelinase activity in cultured skin fibroblasts from a fetus affected with infantile-type Niemann-Pick disease was 0.5% of control activity; the activities in cells from two patients with adult-type disease (Cases 2 and 3) were 5.0% and 59.0%. Sphingomyelinase activiy was separated into three peaks (I-III) by isoelectric focusing. The isoelectric points were 4.5, 4.9, and 5.2 for peaks I, II, and III, respectively. The three peaks in the Case 2 cells were drastically reduced; only a very small peak could be distinguished (pI of 4.7). On the other hand, three peaks were observed in the Case 3 cells. Peak I had a pI of 4.4, peak II a pI of 4.7, and peak III a pI of 5.2. Peak I was found at near normal level, but both peaks II and III were markedly reduced. Sphingomyelinase in the peak I fraction obtained from isoelectric focusing in Case 3 cells was found to have the same Km value as that in control cells.", "contents": "Sphingomyelinase activities in cultured skin fibroblasts from patients with Niemann-Pick Disease. Sphingomyelinase activity in cultured skin fibroblasts from a fetus affected with infantile-type Niemann-Pick disease was 0.5% of control activity; the activities in cells from two patients with adult-type disease (Cases 2 and 3) were 5.0% and 59.0%. Sphingomyelinase activiy was separated into three peaks (I-III) by isoelectric focusing. The isoelectric points were 4.5, 4.9, and 5.2 for peaks I, II, and III, respectively. The three peaks in the Case 2 cells were drastically reduced; only a very small peak could be distinguished (pI of 4.7). On the other hand, three peaks were observed in the Case 3 cells. Peak I had a pI of 4.4, peak II a pI of 4.7, and peak III a pI of 5.2. Peak I was found at near normal level, but both peaks II and III were markedly reduced. Sphingomyelinase in the peak I fraction obtained from isoelectric focusing in Case 3 cells was found to have the same Km value as that in control cells."}
{"id": "PMID:220178", "title": "Hormone interactions in the Sertoli cells.", "content": "The effects of follicle-stimulating hormone (FSH) and testosterone in rat Sertoli cells were investigated in vitro by means of isolated cell populations. The Sertoli cells selectively bind FSH, and respond to FSH stimulation with increased accumulation of endogenous cyclic AMP and secretion of androgen-binding protein (ABP). FSH binding and cyclic AMP response in the Sertoli cells change dramatically during sexual maturation. Cyclic AMP response decreases despite an increase in FSH-binding receptors per cell. Evidence has been provided for the existence of cytoplasmic and nuclear androgen receptors and chromatin acceptor-sites that specifically bind the androgen-receptor complex in the Sertoli cells. A model has been proposed for the hormonal interactions in the seminiferous tubule and the possible role of Sertoli cells in mediating the hormonal effects on spermatogenesis.", "contents": "Hormone interactions in the Sertoli cells. The effects of follicle-stimulating hormone (FSH) and testosterone in rat Sertoli cells were investigated in vitro by means of isolated cell populations. The Sertoli cells selectively bind FSH, and respond to FSH stimulation with increased accumulation of endogenous cyclic AMP and secretion of androgen-binding protein (ABP). FSH binding and cyclic AMP response in the Sertoli cells change dramatically during sexual maturation. Cyclic AMP response decreases despite an increase in FSH-binding receptors per cell. Evidence has been provided for the existence of cytoplasmic and nuclear androgen receptors and chromatin acceptor-sites that specifically bind the androgen-receptor complex in the Sertoli cells. A model has been proposed for the hormonal interactions in the seminiferous tubule and the possible role of Sertoli cells in mediating the hormonal effects on spermatogenesis."}
{"id": "PMID:220179", "title": "Cytolytic activity in vitro of lymph node cells after exposure in vivo to tumor cells suspended in blocking sera.", "content": "The in vivo effect of blocking sera (bs) on both tumor growth and subsequent in vitro cytolytic activity of regional lymph node cells was determined following injection of hepatoma cells suspended in normal sera (ns) or bs into the hind footpads of guinea pigs. Tumor growth was unaffected by bs but the primary response to tumor by LNC draining tumor/bs sites was significantly lower in 4/6 experiments as compared to cells from lymph nodes draining tumor/ns sites.", "contents": "Cytolytic activity in vitro of lymph node cells after exposure in vivo to tumor cells suspended in blocking sera. The in vivo effect of blocking sera (bs) on both tumor growth and subsequent in vitro cytolytic activity of regional lymph node cells was determined following injection of hepatoma cells suspended in normal sera (ns) or bs into the hind footpads of guinea pigs. Tumor growth was unaffected by bs but the primary response to tumor by LNC draining tumor/bs sites was significantly lower in 4/6 experiments as compared to cells from lymph nodes draining tumor/ns sites."}
{"id": "PMID:220180", "title": "Interference of simultaneous skin tests in delayed hypersensitivity.", "content": "The interference of two simultaneous skin test reactions of intermediate strength has been studied in the guinea-pig, using four different antigens, i.e. ovalbumin, horse cytochrome c, PPD and oxazolone. Skin test reactions were evaluated at 4, 24 and 48 h by measuring three parameters: increase in skin thickness, diameter of erythema and intensity of erythema. When an Arthus reaction was elicited simultaneously with a delayed hypersensitivity (DH) reaction, no effect on the DH reaction was observed. When two simultaneous DH reactions were elicited with different antigens, the risk of interference appeared to be rather small. When, however, the same antigen was used for both skin tests, suppression of at least one parameter of a DH-reaction was found in almost all experiments. Suppression of one skin test by another one could not be reduced by introducing a large distance between the two skin tests. As complete inhibition of either of the parameters never occurred, multiple skin testing may allow one to obtain a qualitative impression of the state of delayed hypersensitivity; when, however, reliable quantitative data are needed, the performance of more than one skin test at a time should be avoided.", "contents": "Interference of simultaneous skin tests in delayed hypersensitivity. The interference of two simultaneous skin test reactions of intermediate strength has been studied in the guinea-pig, using four different antigens, i.e. ovalbumin, horse cytochrome c, PPD and oxazolone. Skin test reactions were evaluated at 4, 24 and 48 h by measuring three parameters: increase in skin thickness, diameter of erythema and intensity of erythema. When an Arthus reaction was elicited simultaneously with a delayed hypersensitivity (DH) reaction, no effect on the DH reaction was observed. When two simultaneous DH reactions were elicited with different antigens, the risk of interference appeared to be rather small. When, however, the same antigen was used for both skin tests, suppression of at least one parameter of a DH-reaction was found in almost all experiments. Suppression of one skin test by another one could not be reduced by introducing a large distance between the two skin tests. As complete inhibition of either of the parameters never occurred, multiple skin testing may allow one to obtain a qualitative impression of the state of delayed hypersensitivity; when, however, reliable quantitative data are needed, the performance of more than one skin test at a time should be avoided."}
{"id": "PMID:220181", "title": "Spontaneous and induced cytotoxic properties of human adherent mononuclear cells: killing of non-sensitized and antibody-coated non-erythroid cells.", "content": "A method is described which demonstrates that human adherent mononuclear cells have a strong capacity to kill human nucleated target cells. Cytotoxicity was measured by the release of 51chromium from two established cell lines. Freshly prepared monolayers killed both non-sensitized and anti-body coated K562 and CLA-4 target cells. These spontaneous events decreased after short term culture. A second peak of cytotoxic activity was induced by activating the effector cells with endotoxin-treated serum or phytohaemagglutinin. Cytotoxicity was inhibited by silica particles. Studies with alpha-naphthyl esterase showed that 95% of freshly prepared cells and 99% of monolayers cultured for 68 h were monocytes. These studies suggest that adherent monocytes are the predominant cytotoxic effector cell although a contributing effect by the small numbers of contaminating lymphocytes can not be excluded. Evaluation of monocyte cytotoxicity should have a useful role in clinical investigation.", "contents": "Spontaneous and induced cytotoxic properties of human adherent mononuclear cells: killing of non-sensitized and antibody-coated non-erythroid cells. A method is described which demonstrates that human adherent mononuclear cells have a strong capacity to kill human nucleated target cells. Cytotoxicity was measured by the release of 51chromium from two established cell lines. Freshly prepared monolayers killed both non-sensitized and anti-body coated K562 and CLA-4 target cells. These spontaneous events decreased after short term culture. A second peak of cytotoxic activity was induced by activating the effector cells with endotoxin-treated serum or phytohaemagglutinin. Cytotoxicity was inhibited by silica particles. Studies with alpha-naphthyl esterase showed that 95% of freshly prepared cells and 99% of monolayers cultured for 68 h were monocytes. These studies suggest that adherent monocytes are the predominant cytotoxic effector cell although a contributing effect by the small numbers of contaminating lymphocytes can not be excluded. Evaluation of monocyte cytotoxicity should have a useful role in clinical investigation."}
{"id": "PMID:220182", "title": "The role of locomotion in lymphocyte migration.", "content": "In this study, the role of cell locomotion in lymphocyte traffic was investigated following the in vivo fate of 51Cr labelled lymph node cells pretreated in vitro with substances known to modify cell motility. The results obtained show that lymphocyte migration is an energy dependent process, as it could be impaired by sodium azide. That it requires the integrity of microfilaments, as it was modified by Cytochalasin B; and that it is altered by isoproterenol, theophylline, prostaglandin E1 and dibutyryl cyclic-AMP. The relevance of these findings to the process of lymphocyte recirculation is discussed.", "contents": "The role of locomotion in lymphocyte migration. In this study, the role of cell locomotion in lymphocyte traffic was investigated following the in vivo fate of 51Cr labelled lymph node cells pretreated in vitro with substances known to modify cell motility. The results obtained show that lymphocyte migration is an energy dependent process, as it could be impaired by sodium azide. That it requires the integrity of microfilaments, as it was modified by Cytochalasin B; and that it is altered by isoproterenol, theophylline, prostaglandin E1 and dibutyryl cyclic-AMP. The relevance of these findings to the process of lymphocyte recirculation is discussed."}
{"id": "PMID:220183", "title": "Chemical properties of the principle in C. parvum that produces splenomegaly in mice.", "content": "Suspensions of Wellcome C. parvum strain 6134 produce splenomegaly in mice when injected i.p. in amounts as low as 20 microgram. This lymphoreticular stimulatory activity is extremely sensitive to cell breakage and is abolished by heating for 4 h at 100 degrees. Periodate oxidation of the bacteria destroys their capacity to produce splenomegaly and abrogates the agglutination of intact C. parvum by Con A. Mild HCl hydrolysis also abolished the splenomegaly but phenol:chloroform:ether and chloroform:methanol extractions did not. These results suggest that the relevant stimulatory principle in C. parvum is of carbohydrate nature, and most probably present on the surface of the bacterium.", "contents": "Chemical properties of the principle in C. parvum that produces splenomegaly in mice. Suspensions of Wellcome C. parvum strain 6134 produce splenomegaly in mice when injected i.p. in amounts as low as 20 microgram. This lymphoreticular stimulatory activity is extremely sensitive to cell breakage and is abolished by heating for 4 h at 100 degrees. Periodate oxidation of the bacteria destroys their capacity to produce splenomegaly and abrogates the agglutination of intact C. parvum by Con A. Mild HCl hydrolysis also abolished the splenomegaly but phenol:chloroform:ether and chloroform:methanol extractions did not. These results suggest that the relevant stimulatory principle in C. parvum is of carbohydrate nature, and most probably present on the surface of the bacterium."}
{"id": "PMID:220184", "title": "Lymphocyte surface modulation and glycosphingolipids.", "content": "Using the fluorescent antibody method, identical localization of ligand and glycosphingolipids was found in human peripheral blood B lymphocytes patched and capped with polyvalent anti-immunoglobulin. cAMP also showed the same pattern of localization. It is suggested that glycosphingolipids are hydrogen bonded to receptor-bearing membrane macromolecules and are borne with them into the ligand-induced patches and caps. Here the asymmetric carbon chains of the glycosphingolipids modify the local lipid environment, leading to activation of the adenyl cyclase in the membrane which produces the cAMP.", "contents": "Lymphocyte surface modulation and glycosphingolipids. Using the fluorescent antibody method, identical localization of ligand and glycosphingolipids was found in human peripheral blood B lymphocytes patched and capped with polyvalent anti-immunoglobulin. cAMP also showed the same pattern of localization. It is suggested that glycosphingolipids are hydrogen bonded to receptor-bearing membrane macromolecules and are borne with them into the ligand-induced patches and caps. Here the asymmetric carbon chains of the glycosphingolipids modify the local lipid environment, leading to activation of the adenyl cyclase in the membrane which produces the cAMP."}
{"id": "PMID:220196", "title": "Adjuvant for IgE antibody and islet-activating protein in Bordetella pertussis.", "content": "A new purified protein, with a molecular weight of 77,000, isolated from the supernatant of Bordetella pertussis culture fluid and called islet-activating protein (IAP), had adjuvant activity for IgE antibody in addition to leukocytosis-promoting, histamine-sensitizing and islet-activating activities. None of the three subunits (F1, F2 and F3) was biologically active by itself. All of the four activities were recovered in the complexes of subunits F1.3 and F2.3. These results suggest that the activities are brought about by a common factor inherent in B. pertussis.", "contents": "Adjuvant for IgE antibody and islet-activating protein in Bordetella pertussis. A new purified protein, with a molecular weight of 77,000, isolated from the supernatant of Bordetella pertussis culture fluid and called islet-activating protein (IAP), had adjuvant activity for IgE antibody in addition to leukocytosis-promoting, histamine-sensitizing and islet-activating activities. None of the three subunits (F1, F2 and F3) was biologically active by itself. All of the four activities were recovered in the complexes of subunits F1.3 and F2.3. These results suggest that the activities are brought about by a common factor inherent in B. pertussis."}
{"id": "PMID:220197", "title": "Characteristics of a low-molecular-weight factor extracted from mouse tumors that affects in vitro properties of macrophages.", "content": "A dialysable low-molecular-weight factor capable of affecting in  vitro properties of macrophages was extracted from four different mouse tumors. This factor not only modulates closely related properties of peritoneal macrophages such as spreading and migration but also inhibits lipopolysaccharde-induced tumoricidal activity of these cells. It can be extracted not only from tumor tissues but also from tumor cells grown in vitro. The appearance of this factor is unique to tumors and it is not present in detectable quantities in normal tissues. The factor from one of the tumors, Lewis lung carcinoma, was purified extensively and the partially purified factor retains all the above effects on macrophages. It is not sensitive to pronase or a mixture of bovine spleen phosphodiesterase II, E. coli alkaline phosphatase and pancreatic ribonuclease. The factor is lipid-like in character and it is soluble in both organic solvents and aqueous media. It has ionizable group(s) and is anionic at neutral pH but non-ionic under acidic conditions.", "contents": "Characteristics of a low-molecular-weight factor extracted from mouse tumors that affects in vitro properties of macrophages. A dialysable low-molecular-weight factor capable of affecting in  vitro properties of macrophages was extracted from four different mouse tumors. This factor not only modulates closely related properties of peritoneal macrophages such as spreading and migration but also inhibits lipopolysaccharde-induced tumoricidal activity of these cells. It can be extracted not only from tumor tissues but also from tumor cells grown in vitro. The appearance of this factor is unique to tumors and it is not present in detectable quantities in normal tissues. The factor from one of the tumors, Lewis lung carcinoma, was purified extensively and the partially purified factor retains all the above effects on macrophages. It is not sensitive to pronase or a mixture of bovine spleen phosphodiesterase II, E. coli alkaline phosphatase and pancreatic ribonuclease. The factor is lipid-like in character and it is soluble in both organic solvents and aqueous media. It has ionizable group(s) and is anionic at neutral pH but non-ionic under acidic conditions."}
{"id": "PMID:220198", "title": "Neutralization of pseudotypes of vesicular stomatitis virus by sera from avian retrovirus-infected hosts.", "content": "We investigated the capacity of lymphocytes and sera from chickens bearing tumors induced by avian sarcoma viruses (ASV) to interact with phenotypically mixed particles of vesicular stomatitis virus (VSV) and ASV. Immune chicken sera were able to specifically neutralize such VSV pseudotypes. This ability could be absorbed out, however, on purified preparations of avian retroviruses, suggesting that reactivity was primarily against avian retrovirus enveloped components. Supernatant fluids containing phenotypically mixed particles were unable to stimulate division of lymphocytes of tumor-bearing hosts, an ability possessed by culture fluids containing native ASV particles. Polyacrylamide gel analysis was unable to resolve any distinct pseudotype protein, which was not present in either of the parental virus types. Treatment with crude preparations of ultraviolet (UV)-irradiated VSV pseudotype material did not afford immunity against subsequent challenge with live ASV.", "contents": "Neutralization of pseudotypes of vesicular stomatitis virus by sera from avian retrovirus-infected hosts. We investigated the capacity of lymphocytes and sera from chickens bearing tumors induced by avian sarcoma viruses (ASV) to interact with phenotypically mixed particles of vesicular stomatitis virus (VSV) and ASV. Immune chicken sera were able to specifically neutralize such VSV pseudotypes. This ability could be absorbed out, however, on purified preparations of avian retroviruses, suggesting that reactivity was primarily against avian retrovirus enveloped components. Supernatant fluids containing phenotypically mixed particles were unable to stimulate division of lymphocytes of tumor-bearing hosts, an ability possessed by culture fluids containing native ASV particles. Polyacrylamide gel analysis was unable to resolve any distinct pseudotype protein, which was not present in either of the parental virus types. Treatment with crude preparations of ultraviolet (UV)-irradiated VSV pseudotype material did not afford immunity against subsequent challenge with live ASV."}
{"id": "PMID:220199", "title": "Cell surface glycoprotein changes in Epstein-Barr virus-positive and -negative human hematopoietic cell lines.", "content": "It has previously been shown that differential fucose labelling of many normal and homologous tumor cells, followed by proteolytic release and degradation, yields glycopeptides which upon gel filtration shown an increase in fast-eluting glycopeptides for the tumor cells. This technique has now been applied to cell-surface glycoproteins of different human hematopoietic cell lines. These lines included Epstein-Barr virus (EBV)-carrying lymphoblastoid cell lines of presumed non-neoplastic origin, and malignant EBV-genome-positive Burkitt lymphoma and EBV-negative non-Burkitt lymphoma, leukemia and myeloma lines. As compared with normal peripheral lymphocytes, both the lymphoblastoid type of cell lines and the different types of lines of proven malignant ancestry contained the fast-eluting glycopeptides on their cell surface with very few exceptions. It is therefore concluded that (I) malignant conversion of human lymphoid cell in vivo is commonly, but not obligatorily, associated with a specific change in the composition of the fucosyl glycopeptides, and (2) EBV infection of B lymphocytes does not lead only to the well-documented immortalization in vitro but also, as a rule, to the same type of alteration in fucosyl glycopeptides as was demonstrated for the neoplastic cell lines. It proved possible to distinguish several categories of hematopoietic cell lines due to the effect that pretreatment of the glycopeptides with neuraminidase or mild acid exerted on their subsequent chromatographic behavior.", "contents": "Cell surface glycoprotein changes in Epstein-Barr virus-positive and -negative human hematopoietic cell lines. It has previously been shown that differential fucose labelling of many normal and homologous tumor cells, followed by proteolytic release and degradation, yields glycopeptides which upon gel filtration shown an increase in fast-eluting glycopeptides for the tumor cells. This technique has now been applied to cell-surface glycoproteins of different human hematopoietic cell lines. These lines included Epstein-Barr virus (EBV)-carrying lymphoblastoid cell lines of presumed non-neoplastic origin, and malignant EBV-genome-positive Burkitt lymphoma and EBV-negative non-Burkitt lymphoma, leukemia and myeloma lines. As compared with normal peripheral lymphocytes, both the lymphoblastoid type of cell lines and the different types of lines of proven malignant ancestry contained the fast-eluting glycopeptides on their cell surface with very few exceptions. It is therefore concluded that (I) malignant conversion of human lymphoid cell in vivo is commonly, but not obligatorily, associated with a specific change in the composition of the fucosyl glycopeptides, and (2) EBV infection of B lymphocytes does not lead only to the well-documented immortalization in vitro but also, as a rule, to the same type of alteration in fucosyl glycopeptides as was demonstrated for the neoplastic cell lines. It proved possible to distinguish several categories of hematopoietic cell lines due to the effect that pretreatment of the glycopeptides with neuraminidase or mild acid exerted on their subsequent chromatographic behavior."}
{"id": "PMID:220200", "title": "Establishment and characterization of a human null-cell lymphoblastic lymphoma cell line (K-LL-3).", "content": "A new cell line (K-LL-3) with exceptional characteristics was derived from a bone-marrow aspirate from a patient with poorly differentiated lymphoblastic lymphoma. The cell line was established and the cells maintained on agar feeders for over 1 year. The morphology and cytochemical staining of the primary tumor and the cell line were remarkably similar. The growth characteristics, chromosome pattern, cell-surface receptors and Epstein-Barr pattern, cell-surface receptors and Epstein-Barr virus studies clearly differentiated this cell line from non-malignant lymphoblastoid cell lines. The assay technique used was able to correlate in vitro colony growth with the patient's clinical course. The cells grew on the agar as colonies rather than as a single-cell suspension, and individual colonies could be aspirated and successfully passaged. The K-LL-3 cells lacked cell-surface markers (cytoplasmic and surface immunoglobulins, Fc receptors, C3 receptors, SRBC) except HL-A and thus were classified as null cells. These cells were EBNA (Epstein-Barr virus-specific nuclear antigen) negative and had a pseudodiploid 46XY karyotype.", "contents": "Establishment and characterization of a human null-cell lymphoblastic lymphoma cell line (K-LL-3). A new cell line (K-LL-3) with exceptional characteristics was derived from a bone-marrow aspirate from a patient with poorly differentiated lymphoblastic lymphoma. The cell line was established and the cells maintained on agar feeders for over 1 year. The morphology and cytochemical staining of the primary tumor and the cell line were remarkably similar. The growth characteristics, chromosome pattern, cell-surface receptors and Epstein-Barr pattern, cell-surface receptors and Epstein-Barr virus studies clearly differentiated this cell line from non-malignant lymphoblastoid cell lines. The assay technique used was able to correlate in vitro colony growth with the patient's clinical course. The cells grew on the agar as colonies rather than as a single-cell suspension, and individual colonies could be aspirated and successfully passaged. The K-LL-3 cells lacked cell-surface markers (cytoplasmic and surface immunoglobulins, Fc receptors, C3 receptors, SRBC) except HL-A and thus were classified as null cells. These cells were EBNA (Epstein-Barr virus-specific nuclear antigen) negative and had a pseudodiploid 46XY karyotype."}
{"id": "PMID:220201", "title": "Enhancement of 2-acetylaminofluorene liver carcinogenesis in rats fed a choline-devoid diet.", "content": "The effects of feeding a choline-devoid (CD) or a choline-supplemented (CS) diet on the induction of liver tumors in rats by 2-acetylaminofluorene (AAF) were investigated. Male Sprague-Dawley rats were fed either a CD or a CS diet containing 0.0075% AAF. Three to eight animals were killed 1, 3, 4 and 6 months thereafter. Well to moderately well differentiated hepatocellular carcinomas developed in 50% and 75% of rats fed the CD + AAF diet for 4 and 6 months, respectively. Cholangiocarcinomas developed, after 6 months, in 38% of the animals. No tumor developed in rats fed the CS + AAF diet. The results extend to AAF those previously obtained with DL-ethionine and azaserine showing that feeding a CD diet greatly potentiates the induction in rats of liver tumors by chemical carcinogens.", "contents": "Enhancement of 2-acetylaminofluorene liver carcinogenesis in rats fed a choline-devoid diet. The effects of feeding a choline-devoid (CD) or a choline-supplemented (CS) diet on the induction of liver tumors in rats by 2-acetylaminofluorene (AAF) were investigated. Male Sprague-Dawley rats were fed either a CD or a CS diet containing 0.0075% AAF. Three to eight animals were killed 1, 3, 4 and 6 months thereafter. Well to moderately well differentiated hepatocellular carcinomas developed in 50% and 75% of rats fed the CD + AAF diet for 4 and 6 months, respectively. Cholangiocarcinomas developed, after 6 months, in 38% of the animals. No tumor developed in rats fed the CS + AAF diet. The results extend to AAF those previously obtained with DL-ethionine and azaserine showing that feeding a CD diet greatly potentiates the induction in rats of liver tumors by chemical carcinogens."}
{"id": "PMID:220202", "title": "Reproducibility and relation to specific and non-specific anti-tumor resistance of the tumor \"sneaking through\" phenomenon.", "content": "The reproducibility and immunological specificity of the tumor \"sneaking through\" phenomenon and enhancement of tumor growth were studied in syngeneic and random-bred Syrian hamsters by means of a quantitative modification of the transplantation test. After primary challenge the phenomenon was neither observed in normal animals nor in animals effectively immunized against tumor. However, it was regularly observed in some \"immune\" animals after secondary challenge. In primary challenge of animals \"sneaking through\" phenomenon was most often observed in animals pretreated with large doses of heat-inactivated tumor cells. This characteristic could not be transferred with serum of pretreated animals. In contrast to specific tumor immunity, the \"sneaking through\" pbenomenon appeared to be immunologically non-specific. This was observed in cross-transplantation tests with tumor cells bearing different TSTAs. Thus, TSTA is not an inducer and apparently not a target for a response leading to enhancement of tumor growth in pretreated hamsters. Experiments demonstrating enhanced tumor growth in pretreated animals at the same time demonstrate two other possibly more essential findings: (1) normal animals are naturally resistant to transplantation of 1 to about 1 x 10(3) (or more) tumor cells; and (2) this resistance can be totally abrogated by the pretreatment of normal animals with tumor cell preparations. The preliminary data demonstrate that abrogation of natural anti-tumor resistance in adult hamsters subsequently inoculated with SV40 leads to rapid development of primary tumors in such animals. The development of specific anti-tumor immune response in animals treated with inactivated tumor cell preparations was also studied. Significant non-specific inhibition of sponse in Syrian hamsters treated with inactivated syngeneic tumor cells was observed. The data obtained are considered to demonstrate two anti-tumor defense systems in the animal, i.e., non-specific natural resistance and specific anti-tumor immunity. The first seems to be responsible for elimination of low numbers of tumor cells in the normal organism and also to be esseitial for effective induction and functioning of the specific anti-tumor immunity.", "contents": "Reproducibility and relation to specific and non-specific anti-tumor resistance of the tumor \"sneaking through\" phenomenon. The reproducibility and immunological specificity of the tumor \"sneaking through\" phenomenon and enhancement of tumor growth were studied in syngeneic and random-bred Syrian hamsters by means of a quantitative modification of the transplantation test. After primary challenge the phenomenon was neither observed in normal animals nor in animals effectively immunized against tumor. However, it was regularly observed in some \"immune\" animals after secondary challenge. In primary challenge of animals \"sneaking through\" phenomenon was most often observed in animals pretreated with large doses of heat-inactivated tumor cells. This characteristic could not be transferred with serum of pretreated animals. In contrast to specific tumor immunity, the \"sneaking through\" pbenomenon appeared to be immunologically non-specific. This was observed in cross-transplantation tests with tumor cells bearing different TSTAs. Thus, TSTA is not an inducer and apparently not a target for a response leading to enhancement of tumor growth in pretreated hamsters. Experiments demonstrating enhanced tumor growth in pretreated animals at the same time demonstrate two other possibly more essential findings: (1) normal animals are naturally resistant to transplantation of 1 to about 1 x 10(3) (or more) tumor cells; and (2) this resistance can be totally abrogated by the pretreatment of normal animals with tumor cell preparations. The preliminary data demonstrate that abrogation of natural anti-tumor resistance in adult hamsters subsequently inoculated with SV40 leads to rapid development of primary tumors in such animals. The development of specific anti-tumor immune response in animals treated with inactivated tumor cell preparations was also studied. Significant non-specific inhibition of sponse in Syrian hamsters treated with inactivated syngeneic tumor cells was observed. The data obtained are considered to demonstrate two anti-tumor defense systems in the animal, i.e., non-specific natural resistance and specific anti-tumor immunity. The first seems to be responsible for elimination of low numbers of tumor cells in the normal organism and also to be esseitial for effective induction and functioning of the specific anti-tumor immunity."}
{"id": "PMID:220203", "title": "Effect of ACTH on circadian periodicity of nuclear volume and mitotic division in the zona fasciculata externa of the adrenal cortex of mice.", "content": "In cells of the zona fasciculata externa of the adrenal cortex of mice, the maximal value of nuclear volume is observed in evening and night time, while the mitotic peak occurs in the early part of the day. Ten day subcutaneous injection of 1.5 units of ACTH twice in 24 hr produced nuclear hypertrophy and stimulation of mitotic activity of cells of the zona fasciculata externa. The circadian periodicity of nuclear volume in mice injected with ACTH is disturbed, while the circadian rhythm of mitotic activity is retained.", "contents": "Effect of ACTH on circadian periodicity of nuclear volume and mitotic division in the zona fasciculata externa of the adrenal cortex of mice. In cells of the zona fasciculata externa of the adrenal cortex of mice, the maximal value of nuclear volume is observed in evening and night time, while the mitotic peak occurs in the early part of the day. Ten day subcutaneous injection of 1.5 units of ACTH twice in 24 hr produced nuclear hypertrophy and stimulation of mitotic activity of cells of the zona fasciculata externa. The circadian periodicity of nuclear volume in mice injected with ACTH is disturbed, while the circadian rhythm of mitotic activity is retained."}
{"id": "PMID:220208", "title": "Reproductive performance of apparently healthy cattle persistently infected with bovine viral diarrhea virus.", "content": "A Holstein-Friesian bull and three Holstein-Friesian cows were seronegative for bovine viral diarrhea (BVD) virus but were persistently infected with the virus. Virus was isolated from buffy coat cells and nasal and lacrimal secretions during their lifetime, and they remained free of clinical signs of BVD. The three cows were pregnant when purchased, and they gave birth to full-term calves. One calf lived only a few hours, one calf became ill and died within a few days, and one calf became ill and was euthanatized within a few weeks. One cow was then bred and became pregnant but aborted a 7-month fetus. A second cow was bred approximately 5 months after parturition but did not conceive. The third cow was necropsied 6 weeks after calving, because of loss of weight. Although the bull's semen contained BVD virus when seropositive cows were bred, normal calves were born. When seronegative heifers were bred, they became seropositive to BVD virus within two weeks, with higher titers in six weeks. On heifer conceived after one service but aborted a 6-month fetus. Three others continued to have estrous cycles until their titers rose to 1:128, then they conceived and gave birth to normal calves. Another heifer conceived on the first service, had a titer of 1:128 two weeks after breeding, and gave birth to a normal calf.", "contents": "Reproductive performance of apparently healthy cattle persistently infected with bovine viral diarrhea virus. A Holstein-Friesian bull and three Holstein-Friesian cows were seronegative for bovine viral diarrhea (BVD) virus but were persistently infected with the virus. Virus was isolated from buffy coat cells and nasal and lacrimal secretions during their lifetime, and they remained free of clinical signs of BVD. The three cows were pregnant when purchased, and they gave birth to full-term calves. One calf lived only a few hours, one calf became ill and died within a few days, and one calf became ill and was euthanatized within a few weeks. One cow was then bred and became pregnant but aborted a 7-month fetus. A second cow was bred approximately 5 months after parturition but did not conceive. The third cow was necropsied 6 weeks after calving, because of loss of weight. Although the bull's semen contained BVD virus when seropositive cows were bred, normal calves were born. When seronegative heifers were bred, they became seropositive to BVD virus within two weeks, with higher titers in six weeks. On heifer conceived after one service but aborted a 6-month fetus. Three others continued to have estrous cycles until their titers rose to 1:128, then they conceived and gave birth to normal calves. Another heifer conceived on the first service, had a titer of 1:128 two weeks after breeding, and gave birth to a normal calf."}
{"id": "PMID:220209", "title": "Enzymes of pyrimidine metabolism in Mycoplasma mycoides subsp. mycoides.", "content": "The major pathways of ribonucleotide biosynthesis in Mycoplasma mycoides subsp. mycoides have been proposed from studies on its use of radioactive purines and pyrimidines. To interpret more fully the observed pattern of pyrimidine usage, cell extracts of this organism have been assayed for several enzymes associated with the salvage synthesis of pyrimidine nucleotides. M. mycoides possessed uracil phosphoribosyltransferase, uridine phosphorylase, uridine (cytidine) kinase, uridine 5'-monophosphate kinase, and cytidine 5'-triphosphate synthetase. No activity for phosphorolysis of cytidine was detected, and no in vitro conditions were found to give measurable deamination of cytidine. Of the two potential pathways for incorporation of uridine, our data suggest that this precursor would largely undergo initial phosphorolysis to uracil and ribose-1-phosphate. Conversely, cytidine is phosphorylated directly to cytidine 5'-monophosphate in its major utilization, although conversion of cytidine to uracil, uridine, and uridine nucleotide has been observed in vivo, at least when uracil is provided in the growth medium. Measurements of intracellular nucleotide contents and their changes on additions of pyrimidine precursors have allowed suggestions as to the operation of regulatory mechanisms on pyrimidine nucleotide biosynthesis in M. mycoides in vivo. With uracil alone or uracil plus uridine as precursors of pyrimidine ribonucleotides, the regulation of uracil phosphoribosyltransferase and cytidine 5'-triphosphate synthetase is probably most important in determining the rate of pyrimidine nucleotide synthesis. When cytidine supplements uracil in the growth medium, control of cytidine kinase activity would also be important in this regard.", "contents": "Enzymes of pyrimidine metabolism in Mycoplasma mycoides subsp. mycoides. The major pathways of ribonucleotide biosynthesis in Mycoplasma mycoides subsp. mycoides have been proposed from studies on its use of radioactive purines and pyrimidines. To interpret more fully the observed pattern of pyrimidine usage, cell extracts of this organism have been assayed for several enzymes associated with the salvage synthesis of pyrimidine nucleotides. M. mycoides possessed uracil phosphoribosyltransferase, uridine phosphorylase, uridine (cytidine) kinase, uridine 5'-monophosphate kinase, and cytidine 5'-triphosphate synthetase. No activity for phosphorolysis of cytidine was detected, and no in vitro conditions were found to give measurable deamination of cytidine. Of the two potential pathways for incorporation of uridine, our data suggest that this precursor would largely undergo initial phosphorolysis to uracil and ribose-1-phosphate. Conversely, cytidine is phosphorylated directly to cytidine 5'-monophosphate in its major utilization, although conversion of cytidine to uracil, uridine, and uridine nucleotide has been observed in vivo, at least when uracil is provided in the growth medium. Measurements of intracellular nucleotide contents and their changes on additions of pyrimidine precursors have allowed suggestions as to the operation of regulatory mechanisms on pyrimidine nucleotide biosynthesis in M. mycoides in vivo. With uracil alone or uracil plus uridine as precursors of pyrimidine ribonucleotides, the regulation of uracil phosphoribosyltransferase and cytidine 5'-triphosphate synthetase is probably most important in determining the rate of pyrimidine nucleotide synthesis. When cytidine supplements uracil in the growth medium, control of cytidine kinase activity would also be important in this regard."}
{"id": "PMID:220210", "title": "Properties of two cyclic nucleotide-deficient mutants of Neurospora crassa.", "content": "Studies on the crisp-1 (cr-1), cyclic adenosine 3',5'-monophosphate (cAMP)-deficient mutants of Neurospora crassa were undertaken to characterize the response of these mutants to exogenous cyclic nucleotides and cyclic nucleotide analogs. A growth tube bioassay and a radioimmune assay for cyclic nucleotides yielded the following results. (i) 8-Bromo cAMP and N6-monobutyryl cAMP but not dibutyryl cAMP are efficient cAMP analogs in Neurospora, stimulating mycelial elongation of the cr-1 mutants. Exogenous cyclic guanosine 3'5'-monophosphate (cGMP) also stimulates such mycelial elongation. (ii) Both cAMP levels and cGMP levels found in cr-1 mycelia are lower than those in wild type. However, the levels of both cyclic nucleotides are normal in conidia of cr-1. The data on cr-1 mycelia and those reported earlier in Escherichia coli (M. Shibuya, Y. Takebe, and Y. Kaziro (Cell 12:528-528, 1977) show a previously unexpected relationship between cAMP and cGMP metabolism in microorganisms. The semicolonial morphology of another adenylate cyclase-deficient mutant of Neurospora, frost, was not corrected by exogenous cyclic nucleotides or by phosphodiesterase inhibitors indicating that the frost morphology is probably not caused by low endogenous cAMP levels. The low adenylate cyclase activity and the abnormal morphology of frost may be related separately to the linolenate deficiency reported in the mutant.", "contents": "Properties of two cyclic nucleotide-deficient mutants of Neurospora crassa. Studies on the crisp-1 (cr-1), cyclic adenosine 3',5'-monophosphate (cAMP)-deficient mutants of Neurospora crassa were undertaken to characterize the response of these mutants to exogenous cyclic nucleotides and cyclic nucleotide analogs. A growth tube bioassay and a radioimmune assay for cyclic nucleotides yielded the following results. (i) 8-Bromo cAMP and N6-monobutyryl cAMP but not dibutyryl cAMP are efficient cAMP analogs in Neurospora, stimulating mycelial elongation of the cr-1 mutants. Exogenous cyclic guanosine 3'5'-monophosphate (cGMP) also stimulates such mycelial elongation. (ii) Both cAMP levels and cGMP levels found in cr-1 mycelia are lower than those in wild type. However, the levels of both cyclic nucleotides are normal in conidia of cr-1. The data on cr-1 mycelia and those reported earlier in Escherichia coli (M. Shibuya, Y. Takebe, and Y. Kaziro (Cell 12:528-528, 1977) show a previously unexpected relationship between cAMP and cGMP metabolism in microorganisms. The semicolonial morphology of another adenylate cyclase-deficient mutant of Neurospora, frost, was not corrected by exogenous cyclic nucleotides or by phosphodiesterase inhibitors indicating that the frost morphology is probably not caused by low endogenous cAMP levels. The low adenylate cyclase activity and the abnormal morphology of frost may be related separately to the linolenate deficiency reported in the mutant."}
{"id": "PMID:220211", "title": "Pyridine nucleotide cycle of Salmonella typhimurium: isolation and characterization of pncA, pncB, and pncC mutants and utilization of exogenous nicotinamide adenine dinucleotide.", "content": "Mutants of Salmonella typhimurium LT-2 deficient in nicotinamidase activity (pncA) or nicotinic acid phosphoribosyltransferase activity (pncB) were isolated as resistant to analogs of nicotinic acid and nicotinamide. Information obtained from interrupted mating experiments placed the pncA gene at 27 units and the pncB gene at 25 units on the S. typhimurium LT-2 linkage map. A major difference in the location of the pncA gene was found between the S. typhimurium and Escherichia coli linkage maps. The pncA gene is located in a region in which there is a major inversion of the gene order in S. typhimurium as compared to that in E. coli. Growth experiments using double mutants blocked in the de novo pathway to nicotinamide adenine dinucleotide (NAD) (nad) and in the pyridine nucleotide cycle (pnc) at either the pncA or pncB locus, or both, have provided evidence for the existence of an alternate recycling pathway in this organism. Mutants lacking this alternate cycle, pncC, have been isolated and mapped via cotransduction at 0 units. Utilization of exogenous NAD was examined through the use of [14C]carbonyl-labeled NAD and [14C]adenine-labeled NAD. The results of these experiments suggest that NAD is degraded to nicotinamide mononucleotide at the cell surface. A portion of this extracellular nicotinamide mononucleotide is then transported across the cell membrane by nicotinamide mononucleotide glycohydrolase and degraded to nicotinamide in the process. The remaining nicotinamide mononucleotide accumulates extracellularly and will support the growth of nadA pncB mutants which cannot utilize the nicotinamide resulting from the major pathway of NAD degradation. A model is presented for the utilization of exogenous NAD by S. typhimurium LT-2.", "contents": "Pyridine nucleotide cycle of Salmonella typhimurium: isolation and characterization of pncA, pncB, and pncC mutants and utilization of exogenous nicotinamide adenine dinucleotide. Mutants of Salmonella typhimurium LT-2 deficient in nicotinamidase activity (pncA) or nicotinic acid phosphoribosyltransferase activity (pncB) were isolated as resistant to analogs of nicotinic acid and nicotinamide. Information obtained from interrupted mating experiments placed the pncA gene at 27 units and the pncB gene at 25 units on the S. typhimurium LT-2 linkage map. A major difference in the location of the pncA gene was found between the S. typhimurium and Escherichia coli linkage maps. The pncA gene is located in a region in which there is a major inversion of the gene order in S. typhimurium as compared to that in E. coli. Growth experiments using double mutants blocked in the de novo pathway to nicotinamide adenine dinucleotide (NAD) (nad) and in the pyridine nucleotide cycle (pnc) at either the pncA or pncB locus, or both, have provided evidence for the existence of an alternate recycling pathway in this organism. Mutants lacking this alternate cycle, pncC, have been isolated and mapped via cotransduction at 0 units. Utilization of exogenous NAD was examined through the use of [14C]carbonyl-labeled NAD and [14C]adenine-labeled NAD. The results of these experiments suggest that NAD is degraded to nicotinamide mononucleotide at the cell surface. A portion of this extracellular nicotinamide mononucleotide is then transported across the cell membrane by nicotinamide mononucleotide glycohydrolase and degraded to nicotinamide in the process. The remaining nicotinamide mononucleotide accumulates extracellularly and will support the growth of nadA pncB mutants which cannot utilize the nicotinamide resulting from the major pathway of NAD degradation. A model is presented for the utilization of exogenous NAD by S. typhimurium LT-2."}
{"id": "PMID:220212", "title": "Catabolite and transient repression in Escherichia coli do not require enzyme I of the phosphotransferase system.", "content": "Transient and catabolite repression with changes in intracellular concentrations of cyclic adenosine 3',5-monophosphate is produced by glycerol and by glucose-6-phosphate in a strain with a partial deletion of the structural gene for enzyme I of the phosphoenolpyruvate:sugar phosphotransferase system.", "contents": "Catabolite and transient repression in Escherichia coli do not require enzyme I of the phosphotransferase system. Transient and catabolite repression with changes in intracellular concentrations of cyclic adenosine 3',5-monophosphate is produced by glycerol and by glucose-6-phosphate in a strain with a partial deletion of the structural gene for enzyme I of the phosphoenolpyruvate:sugar phosphotransferase system."}
{"id": "PMID:220213", "title": "Control of cyclic adenosine 3',5'-monophosphate levels by depolarizing agents in fungi.", "content": "It has been reported that diverse treatments which depolarize the plasma membrane of Neurospora crassa produce rapid increases in cyclic adenosine 3',5'-monophosphate (cyclic AMP) levels. In the current study, membrane active antibiotics, which are known or putative depolarizing agents, were found to produce similar cyclic AMP increases, not only in N. crassa, but also in the distantly related fungi Saccharomyces cerevisiae and Mucor racemosus. Uncouplers of oxidative phosphorylation, which have been found to depolarize Neurospora, also produced cyclic AMP increases in all three fungi. The time course of the cyclic AMP response to these various treatments was similar in all three fungi. The fungal studies and studies on depolarized central nervous tissue suggest that cyclic AMP increases may be produced in response to plasma membrane depolarization in diverse eucaryotic cells. A model is proposed for eucaryotic microorganisms in which membrane depolarization serves as a signal of breakdown of the plasma membrane integrity. The subsequent cyclic AMP increase, in turn, may mediate cellular response to help protect the plasma membrane from chemical and mechanical threats to its integrity.", "contents": "Control of cyclic adenosine 3',5'-monophosphate levels by depolarizing agents in fungi. It has been reported that diverse treatments which depolarize the plasma membrane of Neurospora crassa produce rapid increases in cyclic adenosine 3',5'-monophosphate (cyclic AMP) levels. In the current study, membrane active antibiotics, which are known or putative depolarizing agents, were found to produce similar cyclic AMP increases, not only in N. crassa, but also in the distantly related fungi Saccharomyces cerevisiae and Mucor racemosus. Uncouplers of oxidative phosphorylation, which have been found to depolarize Neurospora, also produced cyclic AMP increases in all three fungi. The time course of the cyclic AMP response to these various treatments was similar in all three fungi. The fungal studies and studies on depolarized central nervous tissue suggest that cyclic AMP increases may be produced in response to plasma membrane depolarization in diverse eucaryotic cells. A model is proposed for eucaryotic microorganisms in which membrane depolarization serves as a signal of breakdown of the plasma membrane integrity. The subsequent cyclic AMP increase, in turn, may mediate cellular response to help protect the plasma membrane from chemical and mechanical threats to its integrity."}
{"id": "PMID:220214", "title": "Metabolism of carbohydrate derivatives by Pseudomonas acidovorans.", "content": "Wild-type Pseudomonas acidovorans strain A1 was unable to grow on glycerol or glucose as sole source of carbon and energy although it grew well on gluconate. Spontaneous glycerol-positive mutants, which apparently had become permeable to glycerol, were readily isolated, but glucose-positive mutants did not occur. P. acidovorans lacked glucose dehydrogenase and glucokinase, which were sufficient to account for its inability to grow on glucose. Gluconate was degraded exclusively via a noncoordinately induced Entner-Doudoroff pathway. Phosphogluconate dehydrogenase was undetectable. In contrast to P. aeruginosa, P. acidovorans possessed a single glyceraldehyde-phosphate dehydrogenase activity, which was NAD+ specific and constitutive, and an inducible pyruvate kinase. Moreover, growth of glycerol-positive strain K2 on glycerol did not induce any of the enzymes related to metabolism of hexosephosphate derivatives as occurs in fluorescent pseudomonads.", "contents": "Metabolism of carbohydrate derivatives by Pseudomonas acidovorans. Wild-type Pseudomonas acidovorans strain A1 was unable to grow on glycerol or glucose as sole source of carbon and energy although it grew well on gluconate. Spontaneous glycerol-positive mutants, which apparently had become permeable to glycerol, were readily isolated, but glucose-positive mutants did not occur. P. acidovorans lacked glucose dehydrogenase and glucokinase, which were sufficient to account for its inability to grow on glucose. Gluconate was degraded exclusively via a noncoordinately induced Entner-Doudoroff pathway. Phosphogluconate dehydrogenase was undetectable. In contrast to P. aeruginosa, P. acidovorans possessed a single glyceraldehyde-phosphate dehydrogenase activity, which was NAD+ specific and constitutive, and an inducible pyruvate kinase. Moreover, growth of glycerol-positive strain K2 on glycerol did not induce any of the enzymes related to metabolism of hexosephosphate derivatives as occurs in fluorescent pseudomonads."}
{"id": "PMID:220215", "title": "Lipid and cell wall changes in an inositol-requiring mutant of Neurospora crassa.", "content": "An inositol deficiency in the inositol-requiring (inl) mutant of Neurospora crassa led to changes in the composition of the inositol-containing lipids and the cell wall. On deficient levels of inositol, phosphatidyl inositol decreased by 23-fold, di(inositolphosphoryl) ceramide decreased by 4-fold, and monoinositolphosphoryl ceramide increased slightly. The inositol deficiency also led to an aberrant hyphal morphology and changes in both the amount of cell wall and the amino sugar content of the cell wall. The glucosamine content of the cell wall decreased by 50%, the galactosamine increased by 50%, but no significant changes were found in the content of the cell wall amino sugar precursors, or in the amino acid, glucose, or total hexose content of the cell wall. Inositol-containing compounds were found associated with purified cell wall material. These compounds were bound tightly to the cell wall but could be removed by treatment with alkali, a treatment which disrupts the cell wall integrity. Possible mechanisms of how changes in lipid composition can affect cell wall biosynthesis are discussed.", "contents": "Lipid and cell wall changes in an inositol-requiring mutant of Neurospora crassa. An inositol deficiency in the inositol-requiring (inl) mutant of Neurospora crassa led to changes in the composition of the inositol-containing lipids and the cell wall. On deficient levels of inositol, phosphatidyl inositol decreased by 23-fold, di(inositolphosphoryl) ceramide decreased by 4-fold, and monoinositolphosphoryl ceramide increased slightly. The inositol deficiency also led to an aberrant hyphal morphology and changes in both the amount of cell wall and the amino sugar content of the cell wall. The glucosamine content of the cell wall decreased by 50%, the galactosamine increased by 50%, but no significant changes were found in the content of the cell wall amino sugar precursors, or in the amino acid, glucose, or total hexose content of the cell wall. Inositol-containing compounds were found associated with purified cell wall material. These compounds were bound tightly to the cell wall but could be removed by treatment with alkali, a treatment which disrupts the cell wall integrity. Possible mechanisms of how changes in lipid composition can affect cell wall biosynthesis are discussed."}
{"id": "PMID:220217", "title": "The formation of enzyme-bound and medium pyrophosphate and the molecular basis of the oxygen exchange reaction of yeast inorganic pyrophosphatase.", "content": "Yeast inorganic pyrophosphatase, with 10 mM 32Pi and 10 mM Mg2+ present at pH 7.3 TO 7.6, rapidly forms enzyme-bound pyrophosphate equivalent to about 5% of the total catalytic sties on the two enzyme subunits. The enzyme thus appears to bind PPi so as to favor thermodynamically its formation from Pi. The enzyme catalyzes a measurable equilibrium formation of free PPi at a much slower rate. Under similar conditions, the enzyme catalyzes a rapid exchange of oxygen atoms between Pi and water with the relative activation by metals being Mg2+ greater than Zn2+ greater than Co2+ greater than Mn2+. Millisecond mixing and quenching experiments demonstrate that the rate of formation and cleavage of the enzyme-bound PPi is rapid enough to explain most or all of the oxygen exchange reaction.", "contents": "The formation of enzyme-bound and medium pyrophosphate and the molecular basis of the oxygen exchange reaction of yeast inorganic pyrophosphatase. Yeast inorganic pyrophosphatase, with 10 mM 32Pi and 10 mM Mg2+ present at pH 7.3 TO 7.6, rapidly forms enzyme-bound pyrophosphate equivalent to about 5% of the total catalytic sties on the two enzyme subunits. The enzyme thus appears to bind PPi so as to favor thermodynamically its formation from Pi. The enzyme catalyzes a measurable equilibrium formation of free PPi at a much slower rate. Under similar conditions, the enzyme catalyzes a rapid exchange of oxygen atoms between Pi and water with the relative activation by metals being Mg2+ greater than Zn2+ greater than Co2+ greater than Mn2+. Millisecond mixing and quenching experiments demonstrate that the rate of formation and cleavage of the enzyme-bound PPi is rapid enough to explain most or all of the oxygen exchange reaction."}
{"id": "PMID:220218", "title": "Purification, properties, and kinetics of D-ribulokinase from Aerobacter aerogenes.", "content": "The enzyme D-ribulokinase from Aerobacter aerogenes was purified to near homogeneity. The molecular weight, as determined by Sephacryl gel chromatography, is 116,000. The subunit molecular weight, determined by sodium dodecyl sulfate-gel electrophoresis, is 59,000, suggesting that D-ribulokinase is a dimer of identical subunits. Initial rate kinetic studies, involving substrate analogs and products, were carried out. These investigations support a kinetic mechanism of the Random Bi Bi type. Isotope partitioning, utilizing D-[3H]ribulose, indicates that the mechanism is steady state Random Bi Bi.", "contents": "Purification, properties, and kinetics of D-ribulokinase from Aerobacter aerogenes. The enzyme D-ribulokinase from Aerobacter aerogenes was purified to near homogeneity. The molecular weight, as determined by Sephacryl gel chromatography, is 116,000. The subunit molecular weight, determined by sodium dodecyl sulfate-gel electrophoresis, is 59,000, suggesting that D-ribulokinase is a dimer of identical subunits. Initial rate kinetic studies, involving substrate analogs and products, were carried out. These investigations support a kinetic mechanism of the Random Bi Bi type. Isotope partitioning, utilizing D-[3H]ribulose, indicates that the mechanism is steady state Random Bi Bi."}
{"id": "PMID:220224", "title": "Amino acid sequence of subunit V of bovine heart cytochrome oxidase, the heme alpha-containing subunit.", "content": "The complete amino acid sequence of the heme alpha-containing subunit V of bovine heart cytochrome oxidase was determined to be: H2N-Ser-His-Gly-Ser-His-Glu-Thr-Asp-Glu-Glu-Phe-Asp-Ala-Arg-Trp-Val-Thr-Tyr-Phe-Asn-Lys-Pro-Asp-Ile-Asp-Ala-Trp-Glu-Leu-Arg-Lys-Gly-Met-Asn-Thr-Leu-Val-Gly-Tyr-Asp-Leu-Val-Pro-Glu-Pro-Lys-Ile-Ile-Asp-Ala-Ala-Leu-Arg-Ala-Cys-Arg-Arg-Leu-Asn-Asp-Phe-Ala-Ser-Ala-Val-Arg-Ile-Leu-Glu-Val-Val-Lys-Asp-Lys-Ala-Gly-Pro-His-Lys-Glu-Ile-Tyr-Pro-Tyr-Val-Ile-Gln-Glu-Leu-Arg-Pro-Thr-Leu-Asn-Glu-Leu-Gly-Ile-Ser-Thr-Pro-Glu-Glu-Leu-Gly-Leu-Asp-Lys-Val-COOH. The subunit V is a single polypeptide which consists of 109 amino acid residues. The protein contains 48.6% hydrophobic residues and 34.0% hydrophilic residues and it is an acidic protein having a net charge of -3 at neutral pH. The molecular weight of subunit V was calculated to be 12,436 and that for the heme alpha-containing polypeptide was 13,295.", "contents": "Amino acid sequence of subunit V of bovine heart cytochrome oxidase, the heme alpha-containing subunit. The complete amino acid sequence of the heme alpha-containing subunit V of bovine heart cytochrome oxidase was determined to be: H2N-Ser-His-Gly-Ser-His-Glu-Thr-Asp-Glu-Glu-Phe-Asp-Ala-Arg-Trp-Val-Thr-Tyr-Phe-Asn-Lys-Pro-Asp-Ile-Asp-Ala-Trp-Glu-Leu-Arg-Lys-Gly-Met-Asn-Thr-Leu-Val-Gly-Tyr-Asp-Leu-Val-Pro-Glu-Pro-Lys-Ile-Ile-Asp-Ala-Ala-Leu-Arg-Ala-Cys-Arg-Arg-Leu-Asn-Asp-Phe-Ala-Ser-Ala-Val-Arg-Ile-Leu-Glu-Val-Val-Lys-Asp-Lys-Ala-Gly-Pro-His-Lys-Glu-Ile-Tyr-Pro-Tyr-Val-Ile-Gln-Glu-Leu-Arg-Pro-Thr-Leu-Asn-Glu-Leu-Gly-Ile-Ser-Thr-Pro-Glu-Glu-Leu-Gly-Leu-Asp-Lys-Val-COOH. The subunit V is a single polypeptide which consists of 109 amino acid residues. The protein contains 48.6% hydrophobic residues and 34.0% hydrophilic residues and it is an acidic protein having a net charge of -3 at neutral pH. The molecular weight of subunit V was calculated to be 12,436 and that for the heme alpha-containing polypeptide was 13,295."}
{"id": "PMID:220231", "title": "Purification and properties of cyclic AMP-independent glycogen synthase kinase 1 from rabbit skeletal muscle.", "content": "A cyclic AMP-independent casein (phosvitin) kinase eluted from a phosphocellulose column with 0.35 M KCl also possesses glycogen synthase kinase activity. This kinase, designated synthase kinase 1, is separable from other cyclic AMP-independent protein kinases, which also contain glycogen synthase kinase activity, by chromatography on a phosphocellulose column. This kinase was purified 15,000-fold from the crude extract. Synthase kinase activity co-purifies with casein and phosvitin kinase activities. Heat inactivation of these three kinase activities follow similar kinetics. It is suggested that these three kinase activities reside in a single protein. This kinase has a molecular weight of approximately 34,000 as determined by glycerol density gradient centrifugation and by gel filtration. The Km values for the synthase kinase-catalyzed reaction are 0.12 mg/ml (0.35 micronM) for synthase, 12 micronM for ATP, and 0.15 mM for Mg2+. The phosphorylation of glycogen synthase by the kinase results in the incorporation of 4 mol of phosphate/85,000 subunit; however, only two of the phosphate sites predominantly determine the glucose-6-P dependency of the synthase. Synthase kinase activity is sensitive to inhibition by NaCl or KCl at concentrations encountered during purification. Synthase kinase activity is insensitive to the allosteric effector (glucose-6-P) or substrate (UDP-glucose) of glycogen synthase at concentrations usually found under physiological condition.", "contents": "Purification and properties of cyclic AMP-independent glycogen synthase kinase 1 from rabbit skeletal muscle. A cyclic AMP-independent casein (phosvitin) kinase eluted from a phosphocellulose column with 0.35 M KCl also possesses glycogen synthase kinase activity. This kinase, designated synthase kinase 1, is separable from other cyclic AMP-independent protein kinases, which also contain glycogen synthase kinase activity, by chromatography on a phosphocellulose column. This kinase was purified 15,000-fold from the crude extract. Synthase kinase activity co-purifies with casein and phosvitin kinase activities. Heat inactivation of these three kinase activities follow similar kinetics. It is suggested that these three kinase activities reside in a single protein. This kinase has a molecular weight of approximately 34,000 as determined by glycerol density gradient centrifugation and by gel filtration. The Km values for the synthase kinase-catalyzed reaction are 0.12 mg/ml (0.35 micronM) for synthase, 12 micronM for ATP, and 0.15 mM for Mg2+. The phosphorylation of glycogen synthase by the kinase results in the incorporation of 4 mol of phosphate/85,000 subunit; however, only two of the phosphate sites predominantly determine the glucose-6-P dependency of the synthase. Synthase kinase activity is sensitive to inhibition by NaCl or KCl at concentrations encountered during purification. Synthase kinase activity is insensitive to the allosteric effector (glucose-6-P) or substrate (UDP-glucose) of glycogen synthase at concentrations usually found under physiological condition."}
{"id": "PMID:220232", "title": "Resonance Raman and EPR of nitrosyl human hemoglobin and chains, carp hemoglobin, and model compounds. Implications for the nitrosyl heme coordination state.", "content": "We report the joint resonance Raman (RR) and electron paramagnetic resonance (epr) study of five- and six-coordinate nitrosyl heme model compounds and of the titled nitrosyl hemoproteins. Both epr and RR spectra fall into two types which, in the models, correspond to five- and six-coordinate nitrosyl hemes. However, neither RR nor epr spectroscopy is highly sensitive to the nature of the bond between a nitrosyl heme and a coordinated nitrogenous base, nor do the results of one technique uniformly correlate with those of the other. It is not possible to use epr spectroscopy as a test for the coordination state of a nitrosyl heme. The position of the highest frequency (depolarized) RR band possibly provides such a test. Any breaking of the very weak bond between nitrosyl heme and proximal histidine in T state human HbNO is more a consequence of tertiary structural features unique to the human alphaNO chains than it is of properties of the T quaternary conformation.", "contents": "Resonance Raman and EPR of nitrosyl human hemoglobin and chains, carp hemoglobin, and model compounds. Implications for the nitrosyl heme coordination state. We report the joint resonance Raman (RR) and electron paramagnetic resonance (epr) study of five- and six-coordinate nitrosyl heme model compounds and of the titled nitrosyl hemoproteins. Both epr and RR spectra fall into two types which, in the models, correspond to five- and six-coordinate nitrosyl hemes. However, neither RR nor epr spectroscopy is highly sensitive to the nature of the bond between a nitrosyl heme and a coordinated nitrogenous base, nor do the results of one technique uniformly correlate with those of the other. It is not possible to use epr spectroscopy as a test for the coordination state of a nitrosyl heme. The position of the highest frequency (depolarized) RR band possibly provides such a test. Any breaking of the very weak bond between nitrosyl heme and proximal histidine in T state human HbNO is more a consequence of tertiary structural features unique to the human alphaNO chains than it is of properties of the T quaternary conformation."}
{"id": "PMID:220233", "title": "Comparative solvent perturbation of horse heart cytochrome c and Rhodospirillum rubrum cytochrome c2.", "content": "The extent of exposure of heme to solvent in horse heart cytochrome c and Rhodospirillum rubrum c2 was investigated to determine whether a correlation exists between the properties of these oxidation-reduction proteins and their heme environments. Solvent perturbation absorption difference spectra were measured using ethylene glycol, glycerol, and sucrose at concentrations between 0 and 30%. Cytochrome c appears to exhibit a somewhat greater extent of heme exposure than cytochrome c2 for both the oxidized and reduced states. These results suggest that the lower oxidation-reduction potential of cytochrome c may in part be due to a greater extent of exposure of the heme. The oxidized state of both proteins appears to exhibit a greater exposure than that of the reduced state which is consistent with a more favorable environment for the charge on the ferric heme coordination center.", "contents": "Comparative solvent perturbation of horse heart cytochrome c and Rhodospirillum rubrum cytochrome c2. The extent of exposure of heme to solvent in horse heart cytochrome c and Rhodospirillum rubrum c2 was investigated to determine whether a correlation exists between the properties of these oxidation-reduction proteins and their heme environments. Solvent perturbation absorption difference spectra were measured using ethylene glycol, glycerol, and sucrose at concentrations between 0 and 30%. Cytochrome c appears to exhibit a somewhat greater extent of heme exposure than cytochrome c2 for both the oxidized and reduced states. These results suggest that the lower oxidation-reduction potential of cytochrome c may in part be due to a greater extent of exposure of the heme. The oxidized state of both proteins appears to exhibit a greater exposure than that of the reduced state which is consistent with a more favorable environment for the charge on the ferric heme coordination center."}
{"id": "PMID:220234", "title": "Primary site and second site revertants of missense mutants of the evolutionarily invariant tryptophan 64 in iso-1-cytochrome c from yeast.", "content": "The three missense mutants cyc1-132, cyc1-166 and cyc1-189 in the yeast Saccharomyces cerevisiae contain nonfunctional and thermolabile iso-1-cytochromes c and have different replacements of the tryptophan at position 64 which corresponds to the invariant tryptophan residue found in cytochromes c from all eukaryotic species. The cyc1-166 and cyc1-189 mutants contain single replacements of, respectively, serine 64 and cysteine 64, while the cyc1-132 mutant contains a double replacement of glycine 64 and alanine 65 instead of the normal tryptophan 64 and aspartic acid 65. Twenty-three intragenic revertants having at least partially functional iso-1-cytochromes c arose from these three missense mutants by single amino acid replacements of either tryptophan, phenylalanine, tyrosine or leucine at position 64, or by second-site replacements in which the mutant residues at position 64 are retained and the normal serine 45 is replaced by phenylalanine 45. Specific activities of the iso-1-cytochromes c were estimated by growth of strains on lactate medium and are as follows, in terms of the normal, for iso-1-cytochromes c altered specifically in the ways shown: 100% for phenylalanine 64; 25% for tyrosine 64; between 0 and 25% for leucine 64; 100% for phenylalanine 45, cysteine 64; 25% for phenylalanine 45, serine 64; between 0 and 25% for phenylalanine 45, glycine 64, alanine 65; and 0% for serine 64, for cysteine 64, and for glycine 64, alanine 65 iso-1-cytochromes c. The results demonstrate that small residues of glycine, serine, and cysteine at position 64 are incompatible with function; they imply that many of the 10 amino acids accessible by single base-pair substitution but not observed in primary site revertants also are incompatible with function; and they show that large hydrophobic residues of phenylalanine, leucine, and tyrosine at position 64 are capable of restoring at least partial function. The second site revertants indicate that deleterious effects of the three missense mutants can be compensated by the introduction of phenylalanine 45, which may occupy space normally filled by tryptophan 64. Altered shapes of Calpha-band spectra and at least partial instability were characteristics of all iso-1-cytochromes c found lacking tryptophan 64. Apparently, the principal role of the invariant tryptophan is stabilization of the active protein structure, by providing a large hydrophobic group at the proper location.", "contents": "Primary site and second site revertants of missense mutants of the evolutionarily invariant tryptophan 64 in iso-1-cytochrome c from yeast. The three missense mutants cyc1-132, cyc1-166 and cyc1-189 in the yeast Saccharomyces cerevisiae contain nonfunctional and thermolabile iso-1-cytochromes c and have different replacements of the tryptophan at position 64 which corresponds to the invariant tryptophan residue found in cytochromes c from all eukaryotic species. The cyc1-166 and cyc1-189 mutants contain single replacements of, respectively, serine 64 and cysteine 64, while the cyc1-132 mutant contains a double replacement of glycine 64 and alanine 65 instead of the normal tryptophan 64 and aspartic acid 65. Twenty-three intragenic revertants having at least partially functional iso-1-cytochromes c arose from these three missense mutants by single amino acid replacements of either tryptophan, phenylalanine, tyrosine or leucine at position 64, or by second-site replacements in which the mutant residues at position 64 are retained and the normal serine 45 is replaced by phenylalanine 45. Specific activities of the iso-1-cytochromes c were estimated by growth of strains on lactate medium and are as follows, in terms of the normal, for iso-1-cytochromes c altered specifically in the ways shown: 100% for phenylalanine 64; 25% for tyrosine 64; between 0 and 25% for leucine 64; 100% for phenylalanine 45, cysteine 64; 25% for phenylalanine 45, serine 64; between 0 and 25% for phenylalanine 45, glycine 64, alanine 65; and 0% for serine 64, for cysteine 64, and for glycine 64, alanine 65 iso-1-cytochromes c. The results demonstrate that small residues of glycine, serine, and cysteine at position 64 are incompatible with function; they imply that many of the 10 amino acids accessible by single base-pair substitution but not observed in primary site revertants also are incompatible with function; and they show that large hydrophobic residues of phenylalanine, leucine, and tyrosine at position 64 are capable of restoring at least partial function. The second site revertants indicate that deleterious effects of the three missense mutants can be compensated by the introduction of phenylalanine 45, which may occupy space normally filled by tryptophan 64. Altered shapes of Calpha-band spectra and at least partial instability were characteristics of all iso-1-cytochromes c found lacking tryptophan 64. Apparently, the principal role of the invariant tryptophan is stabilization of the active protein structure, by providing a large hydrophobic group at the proper location."}
{"id": "PMID:220237", "title": "Heme-associated subunit complex of cytochrome c oxidase identified by a new two-dimensional gel electrophoresis.", "content": "A Novel two-dimensional system (isoelectric focusing in the first dimension and sodium dodecyl sulfate-urea electrophoresis in the second) was used to determine the pI values of beef heart subunits of cytochrome c oxidase. The results identified a heme-associated complex of Subunits I, II, and IV. Conditions mitigate against migration of free heme.", "contents": "Heme-associated subunit complex of cytochrome c oxidase identified by a new two-dimensional gel electrophoresis. A Novel two-dimensional system (isoelectric focusing in the first dimension and sodium dodecyl sulfate-urea electrophoresis in the second) was used to determine the pI values of beef heart subunits of cytochrome c oxidase. The results identified a heme-associated complex of Subunits I, II, and IV. Conditions mitigate against migration of free heme."}
{"id": "PMID:220238", "title": "Reconstitution into liposomes of the glycoprotein of vesicular stomatitis virus by detergent dialysis.", "content": "The glycoprotein of vesicular stomatitis (VS) virus was selectively liberated from the virion membrane by the dialyzable nonionic detergent, beta-D-octylglucoside. The isolated viral glycoprotein could be rendered virtually free of phospholipid and detergent, under which conditions it formed tail-to-tail glycoprotein micelles in the form of rosettes. When mixtures of viral glycoprotein and egg lecithin were dialyzed free of octylglucoside, glycoprotein vesicles formed spontaneously with spikes protruding in the same external orientation as the VS virion membrane. The glycoprotein vesicles exhibited increased and uniform buoyant density, indicating relative homogeneity in the proportion of glycoprotein and phosphatidylcholine in each glycoprotein liposome. Evidence for similar insertion and orientation of VS viral glycoprotein in both phosphatidylcholine vesicles and virion membrane was substantiated by the finding that proteolytic digestion with thermolysin gave rise to hydrophobic glycoprotein tail fragments in vesicle or virion membranes that migrated identically in polyacrylamide gels.", "contents": "Reconstitution into liposomes of the glycoprotein of vesicular stomatitis virus by detergent dialysis. The glycoprotein of vesicular stomatitis (VS) virus was selectively liberated from the virion membrane by the dialyzable nonionic detergent, beta-D-octylglucoside. The isolated viral glycoprotein could be rendered virtually free of phospholipid and detergent, under which conditions it formed tail-to-tail glycoprotein micelles in the form of rosettes. When mixtures of viral glycoprotein and egg lecithin were dialyzed free of octylglucoside, glycoprotein vesicles formed spontaneously with spikes protruding in the same external orientation as the VS virion membrane. The glycoprotein vesicles exhibited increased and uniform buoyant density, indicating relative homogeneity in the proportion of glycoprotein and phosphatidylcholine in each glycoprotein liposome. Evidence for similar insertion and orientation of VS viral glycoprotein in both phosphatidylcholine vesicles and virion membrane was substantiated by the finding that proteolytic digestion with thermolysin gave rise to hydrophobic glycoprotein tail fragments in vesicle or virion membranes that migrated identically in polyacrylamide gels."}
{"id": "PMID:220239", "title": "Inability of parvalbumin to function as a calcium-dependent activator of cyclic nucleotide phosphodiesterase activity.", "content": "The calcium-sensitive phosphodiesterase-stimulating activity sometimes associated with parvalbumin preparations is due to contaminating (less than 0.1%) amounts of carp muscle CDR (calcium-dependent regulator)-like protein. This protein can be resolved from parvalbumins by Sephadex G-75 chromatography and has many characteristics of the CDR. Parvalbumin itself causes a nonspecific stimulation of phosphodiesterase at all calcium concentrations which, in the presence of CDR, can cause an apparent shift to a lower concentration of the calcium level required for half-maximal stimulation.", "contents": "Inability of parvalbumin to function as a calcium-dependent activator of cyclic nucleotide phosphodiesterase activity. The calcium-sensitive phosphodiesterase-stimulating activity sometimes associated with parvalbumin preparations is due to contaminating (less than 0.1%) amounts of carp muscle CDR (calcium-dependent regulator)-like protein. This protein can be resolved from parvalbumins by Sephadex G-75 chromatography and has many characteristics of the CDR. Parvalbumin itself causes a nonspecific stimulation of phosphodiesterase at all calcium concentrations which, in the presence of CDR, can cause an apparent shift to a lower concentration of the calcium level required for half-maximal stimulation."}
{"id": "PMID:220240", "title": "Measurement of 14N superhyperfine frequencies in stellacyanin by an electron spin echo method.", "content": "We have measured the 14N superhyperfine frequencies for weakly coupled nitrogen in stellacyanin and in a model compound Cu(II)-diethylenetriamine-imidazole using a 3-pulse spin echo technique. By making computer simulations of the superhyperfine spectrum, we have been able to show that these frequencies result from the interaction of the remote protonated nitrogen of metal-bound imidazole with Cu(II).", "contents": "Measurement of 14N superhyperfine frequencies in stellacyanin by an electron spin echo method. We have measured the 14N superhyperfine frequencies for weakly coupled nitrogen in stellacyanin and in a model compound Cu(II)-diethylenetriamine-imidazole using a 3-pulse spin echo technique. By making computer simulations of the superhyperfine spectrum, we have been able to show that these frequencies result from the interaction of the remote protonated nitrogen of metal-bound imidazole with Cu(II)."}
{"id": "PMID:220241", "title": "Regulation of phosphatidylcholine metabolism by cyclic AMP in a model alveolar type 2 cell line.", "content": "The influence of cyclic AMP on the metabolism of phosphatidylcholine, the major component of pulmonary surfactant was examined in a cell line (A549) with type 2 pneumonocyte characteristics. It was found that cyclic AMP increased both the total amount of phosphatidylcholine and disaturated phosphatidylcholine as well as the incorporation of [3H]choline into these fractions. The effect was specific for cyclic AMP since 5'-AMP, adenosine, and cyclic GMP did not alter phosphatidylcholine or disaturated phosphatidylcholine levels. Cyclic AMP had no effect on phosphatidylcholine and disaturated phosphatidylcholine metabolism in another non-type 2 human epithelial cell line (MA-160). Since the ability of various cyclic AMP analogs to increase phosphatidylcholine and disaturated phosphatidylcholine levels was correlated with their ability to activate protein kinase, it seems likely that a protein phosphorylation mechanism is involved in controlling phosphatidylcholine metabolism.", "contents": "Regulation of phosphatidylcholine metabolism by cyclic AMP in a model alveolar type 2 cell line. The influence of cyclic AMP on the metabolism of phosphatidylcholine, the major component of pulmonary surfactant was examined in a cell line (A549) with type 2 pneumonocyte characteristics. It was found that cyclic AMP increased both the total amount of phosphatidylcholine and disaturated phosphatidylcholine as well as the incorporation of [3H]choline into these fractions. The effect was specific for cyclic AMP since 5'-AMP, adenosine, and cyclic GMP did not alter phosphatidylcholine or disaturated phosphatidylcholine levels. Cyclic AMP had no effect on phosphatidylcholine and disaturated phosphatidylcholine metabolism in another non-type 2 human epithelial cell line (MA-160). Since the ability of various cyclic AMP analogs to increase phosphatidylcholine and disaturated phosphatidylcholine levels was correlated with their ability to activate protein kinase, it seems likely that a protein phosphorylation mechanism is involved in controlling phosphatidylcholine metabolism."}
{"id": "PMID:220242", "title": "The stereochemistry of NADH utilization by the flavoenzyme monooxygenase orcinol hydroxylase.", "content": "Ribbons et al. (Ribbons, D.W., Ohta, Y., and Higgins, I.J. (1972) in Molecular Basis of Electron Transport, Miami Winter Symposic Series (Schultz, J., and Cameron, B.F., eds) Vol. 4, pp. 251-274, Academic Press, New York) presented a preliminary report that the flavoenzyme monooxygenase orcinol hydroxylase shows mixed type 4R, 4S stereospecificity with respect to dihydronicotinamide oxidation when resorcinol and m-cresol were used as substrate analogs. With the natural substrate orcinol, 4R chirality was maintained. In kinetic isotope experiments reported here, we demonstrate in fact that orcinol hydroxylase maintains 4R stereospecificity with respect to dihydronicotinamide oxidation with all three substrates, orcinol, resorcinol, and m-cresol. Deuterium and tritium kinetic isotope effects were detected under Vmax conditions with (4R)-[4-2H]-, and (4R)-[4-3H]NADH for all three substrates. No isotope effect was observed with (4S)-[4-2H]NADH and tritium labilization from assays with (4S)-[4-3H]-NADH was negligible in all cases.", "contents": "The stereochemistry of NADH utilization by the flavoenzyme monooxygenase orcinol hydroxylase. Ribbons et al. (Ribbons, D.W., Ohta, Y., and Higgins, I.J. (1972) in Molecular Basis of Electron Transport, Miami Winter Symposic Series (Schultz, J., and Cameron, B.F., eds) Vol. 4, pp. 251-274, Academic Press, New York) presented a preliminary report that the flavoenzyme monooxygenase orcinol hydroxylase shows mixed type 4R, 4S stereospecificity with respect to dihydronicotinamide oxidation when resorcinol and m-cresol were used as substrate analogs. With the natural substrate orcinol, 4R chirality was maintained. In kinetic isotope experiments reported here, we demonstrate in fact that orcinol hydroxylase maintains 4R stereospecificity with respect to dihydronicotinamide oxidation with all three substrates, orcinol, resorcinol, and m-cresol. Deuterium and tritium kinetic isotope effects were detected under Vmax conditions with (4R)-[4-2H]-, and (4R)-[4-3H]NADH for all three substrates. No isotope effect was observed with (4S)-[4-2H]NADH and tritium labilization from assays with (4S)-[4-3H]-NADH was negligible in all cases."}
{"id": "PMID:220243", "title": "Purification of a cyclic nucleotide phosphodiesterase from bovine brain using blue dextran-Sepharose chromatography.", "content": "The soluble high Km form of cyclic nucleotide phosphodiesterase (EC 3.4.1.17) was purified over 2000-fold from bovine brain homogenates principally using blue dextran-Sepharose chromatography. The purified protein has a specific enzymic activity of 167 units/mg and appears homogeneous when examined by polyacrylamide gel electrophoresis. The enzyme has a molecular weight of 1.26 +/- 0.05 x 10(5) consisting of two apparently identical polypeptide chains. Kinetic measurements indicate that the substrates cyclic GMP and cyclic AMP each have a single Km value, 9 +/- 1 micron and 150 +/- 50 micron, respectively, that the two cyclic nucleotides compete for the same catalytic site, that the blue dye of blue dextran-Sepharose is a competitive inhibitor for the cyclic nucleotides, and that the Vmax with cyclic AMP as substrate is about an order of magnitude larger than that for cyclic GMP. Bovine brain calmodulin stimulates the catalytic rate of the purified enzyme in the presence of Ca2+ by increasing the Vmax associated with each cyclic nucleotide substrate.", "contents": "Purification of a cyclic nucleotide phosphodiesterase from bovine brain using blue dextran-Sepharose chromatography. The soluble high Km form of cyclic nucleotide phosphodiesterase (EC 3.4.1.17) was purified over 2000-fold from bovine brain homogenates principally using blue dextran-Sepharose chromatography. The purified protein has a specific enzymic activity of 167 units/mg and appears homogeneous when examined by polyacrylamide gel electrophoresis. The enzyme has a molecular weight of 1.26 +/- 0.05 x 10(5) consisting of two apparently identical polypeptide chains. Kinetic measurements indicate that the substrates cyclic GMP and cyclic AMP each have a single Km value, 9 +/- 1 micron and 150 +/- 50 micron, respectively, that the two cyclic nucleotides compete for the same catalytic site, that the blue dye of blue dextran-Sepharose is a competitive inhibitor for the cyclic nucleotides, and that the Vmax with cyclic AMP as substrate is about an order of magnitude larger than that for cyclic GMP. Bovine brain calmodulin stimulates the catalytic rate of the purified enzyme in the presence of Ca2+ by increasing the Vmax associated with each cyclic nucleotide substrate."}
{"id": "PMID:220247", "title": "Determination of cooperative interaction between clusters in Clostridium pasteurianum 2 (4Fe-4S) ferredoxin.", "content": "The effect of reducing one 4Fe-4S cluster in Clostridium pasteurianum 2 (4Fe-4S) ferredoxin on the reduction potential of the unreduced cluster has been investigated. While such an effect is suggested by both the x-ray structure of Peptococcus aerogenes 2 (4F-4S) ferredoxin and the polypeptide conformational change on reduction present in clostridial-type 2 (4Fe-4S) ferredoxins, present studies indicate that cluster-cluster cooperative interaction is not strong enough to be of functional importance in these proteins.", "contents": "Determination of cooperative interaction between clusters in Clostridium pasteurianum 2 (4Fe-4S) ferredoxin. The effect of reducing one 4Fe-4S cluster in Clostridium pasteurianum 2 (4Fe-4S) ferredoxin on the reduction potential of the unreduced cluster has been investigated. While such an effect is suggested by both the x-ray structure of Peptococcus aerogenes 2 (4F-4S) ferredoxin and the polypeptide conformational change on reduction present in clostridial-type 2 (4Fe-4S) ferredoxins, present studies indicate that cluster-cluster cooperative interaction is not strong enough to be of functional importance in these proteins."}
{"id": "PMID:220248", "title": "Subunit inequivalence in superoxide anion formation during photooxidation of human oxyhemoglobin.", "content": "Subunit inequivalence in the photooxidation of human oxyhemoglobin was investigated by quantitative analysis of the fraction of alpha and beta chains oxidized after low intensity flash photolysis using white light in quartz cuvettes. This reaction was previously shown to generate methemoglobin and superoxide anion as photoproducts (Demma, L.S., and Salhany, J.M. (1977) J. Biol. Chem. 252, 1226-1230). The present results indicate that superoxide anion photodissociates from the alpha chain about 3 to 4 times more extensively than from beta. This difference was observed in the presence of superoxide dismutase and catalase at both pH 7 and 9, suggesting that photolysis is directly responsible. The reaction of superoxide anion with oxyhemoglobin was also studied with the same analytical methods and no chain differences could be observed. If the electronic structure of the oxyheme complex is viewed as a spin equilibrium between a singlet ground state and a charge transfer configuration, our results may indicate that the uv component of white light perturbs this equilibrium to a greater extent in the oxygenated alpha chain, implying that the separation of energy levels may be smaller in that chain as compared with beta.", "contents": "Subunit inequivalence in superoxide anion formation during photooxidation of human oxyhemoglobin. Subunit inequivalence in the photooxidation of human oxyhemoglobin was investigated by quantitative analysis of the fraction of alpha and beta chains oxidized after low intensity flash photolysis using white light in quartz cuvettes. This reaction was previously shown to generate methemoglobin and superoxide anion as photoproducts (Demma, L.S., and Salhany, J.M. (1977) J. Biol. Chem. 252, 1226-1230). The present results indicate that superoxide anion photodissociates from the alpha chain about 3 to 4 times more extensively than from beta. This difference was observed in the presence of superoxide dismutase and catalase at both pH 7 and 9, suggesting that photolysis is directly responsible. The reaction of superoxide anion with oxyhemoglobin was also studied with the same analytical methods and no chain differences could be observed. If the electronic structure of the oxyheme complex is viewed as a spin equilibrium between a singlet ground state and a charge transfer configuration, our results may indicate that the uv component of white light perturbs this equilibrium to a greater extent in the oxygenated alpha chain, implying that the separation of energy levels may be smaller in that chain as compared with beta."}
{"id": "PMID:220249", "title": "Optical detection of a red-shifted Michaelis complex in the reaction of HCN with ferromyeloperoxidase. Evidence for conformational stabilization of high spin iron (II).", "content": "The reaction of HCN with ferromyeloperoxidase involves the sequential formation of two monocyanide complexes. The first complex, which forms immediately on mixing, is characterized by a red shift in the Soret band of the ferroperoxidase, and a dissociation constant (measured as a Michaelis constant) of 0.67 mM. The second complex arises from the first via a first order process, whose maximal rate is 0.095 s-1 at 25 degrees C, pH 7.0. This more stable complex is characterized by a blue shift in the Soret and alpha bands and by an overall dissociation constant in the region of 4.5 microM. This gives a free energy difference between the two complexes of around 3.0 kcal mol-1 and a difference in optical absorption of 15 nm (Soret). The measured Arrhenius activation energy for the conversion of the high energy, long wavelength complex to the low energy, short wavelength complex is 16.3 kcal mol-1. A larger blue shift is observed on protein denaturation (34 nm), after which the two-step binding reaction is not observed. This, and the magnitude of the activation energy in the spontaneous complex interconversion process, shows that the latter is a conformational process. In addition, it can be concluded that the unknown structural feature of the heme site which is responsible for the anomalous red shift in the optical spectrum of native ferromyeloperoxidase, is also the link between the ligand state of the iron and the protein conformation.", "contents": "Optical detection of a red-shifted Michaelis complex in the reaction of HCN with ferromyeloperoxidase. Evidence for conformational stabilization of high spin iron (II). The reaction of HCN with ferromyeloperoxidase involves the sequential formation of two monocyanide complexes. The first complex, which forms immediately on mixing, is characterized by a red shift in the Soret band of the ferroperoxidase, and a dissociation constant (measured as a Michaelis constant) of 0.67 mM. The second complex arises from the first via a first order process, whose maximal rate is 0.095 s-1 at 25 degrees C, pH 7.0. This more stable complex is characterized by a blue shift in the Soret and alpha bands and by an overall dissociation constant in the region of 4.5 microM. This gives a free energy difference between the two complexes of around 3.0 kcal mol-1 and a difference in optical absorption of 15 nm (Soret). The measured Arrhenius activation energy for the conversion of the high energy, long wavelength complex to the low energy, short wavelength complex is 16.3 kcal mol-1. A larger blue shift is observed on protein denaturation (34 nm), after which the two-step binding reaction is not observed. This, and the magnitude of the activation energy in the spontaneous complex interconversion process, shows that the latter is a conformational process. In addition, it can be concluded that the unknown structural feature of the heme site which is responsible for the anomalous red shift in the optical spectrum of native ferromyeloperoxidase, is also the link between the ligand state of the iron and the protein conformation."}
{"id": "PMID:220250", "title": "(Na+ + K+)-adenosine triphosphatase of mammalian brain. Catalytic and regulatory K+ sites distinguishable by selectivity for Li+.", "content": "Li+, K+, and Rb+ are compared as activators of the hydrolysis of p-nitrophenylphosphate by beef brain (Na+ + K+)-ATPase. Previous experiments have established two classes of K+ binding sites that are involved in this reaction: \"catalytic sites\" have the higher affinity, their occupation is essential for catalytic activity, and they appear to correspond to the extracellular binding sites for active K+ transport; regulatory sites appear to have an allosteric function to \"unmask\" the catalytic sites. A separate set of Na+-binding regulatory sites bring about a similar unmasking of catalytic sites under phosphorylating conditions. Rb+ can activate p-nitrophenylphosphate hydrolysis both in the presence and absence of Na+ and, thus, can interact effectively with both K+ regulatory and catalytic sites. Li+ does not activate p-nitrophenylphosphate hydrolysis at 25 degrees C in the absence of other monovalent ligands. Li+ does activate when the catalytic sites are exposed by Na+ + ATP. Thus, K+ regulatory and catalytic sites differ in their cation selectivity. At temperatures less than 25 degrees C Li+ is able to activate the phosphatase reaction in the absence of other monovalent ligands: maximum activity occurs at 10-12 degrees C. A plot of the ratio, Li+ activation/K+ activation, as a function of temperature shows that the allosteric transition that unmasks catalytic sites occurs spontaneously with decreasing temperatures.", "contents": "(Na+ + K+)-adenosine triphosphatase of mammalian brain. Catalytic and regulatory K+ sites distinguishable by selectivity for Li+. Li+, K+, and Rb+ are compared as activators of the hydrolysis of p-nitrophenylphosphate by beef brain (Na+ + K+)-ATPase. Previous experiments have established two classes of K+ binding sites that are involved in this reaction: \"catalytic sites\" have the higher affinity, their occupation is essential for catalytic activity, and they appear to correspond to the extracellular binding sites for active K+ transport; regulatory sites appear to have an allosteric function to \"unmask\" the catalytic sites. A separate set of Na+-binding regulatory sites bring about a similar unmasking of catalytic sites under phosphorylating conditions. Rb+ can activate p-nitrophenylphosphate hydrolysis both in the presence and absence of Na+ and, thus, can interact effectively with both K+ regulatory and catalytic sites. Li+ does not activate p-nitrophenylphosphate hydrolysis at 25 degrees C in the absence of other monovalent ligands. Li+ does activate when the catalytic sites are exposed by Na+ + ATP. Thus, K+ regulatory and catalytic sites differ in their cation selectivity. At temperatures less than 25 degrees C Li+ is able to activate the phosphatase reaction in the absence of other monovalent ligands: maximum activity occurs at 10-12 degrees C. A plot of the ratio, Li+ activation/K+ activation, as a function of temperature shows that the allosteric transition that unmasks catalytic sites occurs spontaneously with decreasing temperatures."}
{"id": "PMID:220251", "title": "Arrangement of glucose residues in the lipid-linked oligosaccharide precursor of asparaginyl oligosaccharides.", "content": "The lipid-linked oligosaccharide synthesized in vitro, in the presence of 1.0 microM UDP-[3H]Glc, GDP-[14C]Man, and UDP-GlcNAc has been isolated and the structure of the oligosaccharide has been analyzed. The oligosaccharide contains 2 N-acetylglucosamine, 9 mannose, and 3 glucose residues. The N-acetylglucosamine residues are located at the reducing terminus. The 3 glucose residues are arranged in a linear order at one of the nonreducing termini in the sequence Glc 1,2--Glc 1,3--Glc--(Man)9 (GlcNAc)2. The structural analysis was made possible largely by the availability of glucosidase preparations of fungal anad microsomal origin which remove glucose residues from the oligosaccharide without releasing mannose residues.", "contents": "Arrangement of glucose residues in the lipid-linked oligosaccharide precursor of asparaginyl oligosaccharides. The lipid-linked oligosaccharide synthesized in vitro, in the presence of 1.0 microM UDP-[3H]Glc, GDP-[14C]Man, and UDP-GlcNAc has been isolated and the structure of the oligosaccharide has been analyzed. The oligosaccharide contains 2 N-acetylglucosamine, 9 mannose, and 3 glucose residues. The N-acetylglucosamine residues are located at the reducing terminus. The 3 glucose residues are arranged in a linear order at one of the nonreducing termini in the sequence Glc 1,2--Glc 1,3--Glc--(Man)9 (GlcNAc)2. The structural analysis was made possible largely by the availability of glucosidase preparations of fungal anad microsomal origin which remove glucose residues from the oligosaccharide without releasing mannose residues."}
{"id": "PMID:220255", "title": "Coordinate overproduction of orotate phosphoribosyltransferase and orotidine-5'-phosphate decarboxylase in hamster cells resistant to pyrazofurin and 6-azauridine.", "content": "Cells resistant to pyrazofurin and 6-azauridine have been selected from a simian virus 40-transformed Syrian hamster line and from a Chinese hamster lung line. By increasing the concentrations of inhibitors in several steps, mutant cells from both lines have been obtained which resist high concentrations (1 to 5 mM) of the two inhibitors separately or together. Orotidine-5'-phosphate decarboxylase (EC 4.1.1.23), the sixth and last enzyme in UMP biosynthesis, is inhibited by the nucleoside monophosphates derived from pyrazofurin or 6-azauridine. The activity of this enzyme is increased in each resistant cell line tested. Furthermore, there is a parallel increase in each case in the activity of the fifth enzyme of the pathway, orotate phosphoribosyltransferase (EC 2.4.2.10), which is not inhibited by pyrazofurin or 6-azauridine monophosphates, and the amount of increase is up to 67 times the level found in wild type cells. In contrast, the activities of the first three enzymes of UMP biosynthesis remain essentially unchanged in the mutants. Resistant Chinese hamster cells remain sensitive to 5-fluorouridine; this indicates that uridine kinase, the enzyme necessary to convert 6-azauridine to the monophosphate, is still functional.", "contents": "Coordinate overproduction of orotate phosphoribosyltransferase and orotidine-5'-phosphate decarboxylase in hamster cells resistant to pyrazofurin and 6-azauridine. Cells resistant to pyrazofurin and 6-azauridine have been selected from a simian virus 40-transformed Syrian hamster line and from a Chinese hamster lung line. By increasing the concentrations of inhibitors in several steps, mutant cells from both lines have been obtained which resist high concentrations (1 to 5 mM) of the two inhibitors separately or together. Orotidine-5'-phosphate decarboxylase (EC 4.1.1.23), the sixth and last enzyme in UMP biosynthesis, is inhibited by the nucleoside monophosphates derived from pyrazofurin or 6-azauridine. The activity of this enzyme is increased in each resistant cell line tested. Furthermore, there is a parallel increase in each case in the activity of the fifth enzyme of the pathway, orotate phosphoribosyltransferase (EC 2.4.2.10), which is not inhibited by pyrazofurin or 6-azauridine monophosphates, and the amount of increase is up to 67 times the level found in wild type cells. In contrast, the activities of the first three enzymes of UMP biosynthesis remain essentially unchanged in the mutants. Resistant Chinese hamster cells remain sensitive to 5-fluorouridine; this indicates that uridine kinase, the enzyme necessary to convert 6-azauridine to the monophosphate, is still functional."}
{"id": "PMID:220258", "title": "Kinetic studies of bovine liver fructose-1,6-bisphosphatase.", "content": "Initial rate kinetic studies with bovine liver fructose-1,6-bisphosphatase were carried out in both directions of the reaction to determine the sequence of product release from the enzyme. Product inhibition by fructose-6-P was found to be S-linear, I-linear noncompetitive relative to fructose-1,6-bisphosphate, whereas inorganic orthophosphate was determined to be linear competitive with respect to the substrate. The kinetics of the reverse reaction were studied by coupling the phosphatase reaction to the aldolase, triosephosphate isomerase, and glycerolphosphate dehydrogenase reactions. The kinetic results were found to be in harmony with the Uni Bi ordered and random sequential mechanisms as well as a Uni Bi ping-pong mechanism. The nomenclature is that of Cleland (Cleland, W.W. (1963) Biochim. Biophys. Acta 67, 104-137). However, nonkinetic considerations, when taken together with the kinetic results, suggest that the steady state ordered Uni Bi mechanism is the most likely possibility. There is evidence that isomerization of the binary complex of enzyme and phosphate occurs in the kinetic mechanism. Although magnesium is required for the reverse reaction, there is no evidence to suggest that the enzyme discriminates between the magnesium-associated or divalent cation-free forms of the substrates.", "contents": "Kinetic studies of bovine liver fructose-1,6-bisphosphatase. Initial rate kinetic studies with bovine liver fructose-1,6-bisphosphatase were carried out in both directions of the reaction to determine the sequence of product release from the enzyme. Product inhibition by fructose-6-P was found to be S-linear, I-linear noncompetitive relative to fructose-1,6-bisphosphate, whereas inorganic orthophosphate was determined to be linear competitive with respect to the substrate. The kinetics of the reverse reaction were studied by coupling the phosphatase reaction to the aldolase, triosephosphate isomerase, and glycerolphosphate dehydrogenase reactions. The kinetic results were found to be in harmony with the Uni Bi ordered and random sequential mechanisms as well as a Uni Bi ping-pong mechanism. The nomenclature is that of Cleland (Cleland, W.W. (1963) Biochim. Biophys. Acta 67, 104-137). However, nonkinetic considerations, when taken together with the kinetic results, suggest that the steady state ordered Uni Bi mechanism is the most likely possibility. There is evidence that isomerization of the binary complex of enzyme and phosphate occurs in the kinetic mechanism. Although magnesium is required for the reverse reaction, there is no evidence to suggest that the enzyme discriminates between the magnesium-associated or divalent cation-free forms of the substrates."}
{"id": "PMID:220260", "title": "Oxidation-reduction ratio studies of mitochondria in freeze-trapped samples. NADH and flavoprotein fluorescence signals.", "content": "The recording of oxidation-reduction-related fluorescence signals of oxidized flavoprotein (Fp) and reduced pyridine nucleotide (PN) from isolated mitochondria at temperatures below -80 degrees C can be accompanished with a high degree of accuracy and a wide dynamic range. The specific low temperature enhancement of the fluorescence signals due to increased quantum yield and to multiple scattering affords increased accuracy and less interference due to screening pigments such as hemoglobin and myoglobin. Since the metabolic processes are arrested and the recording speed can be greatly diminished, the technique can operate with a much smaller concentration of mitochondria than is needed at room temperature, and the method is suitable for localized oxidation-reduction measurements. The Fp and PN signals originate from the mitochondrial matrix space in which they represent the major fluorochromes. Since Fp and PN are near oxidation-reduction equilibrium, the ratio of the two fluorescence intensities, suitably normalized, approximates the oxidation-reduction ratio of oxidized flavoprotein/reduced pyridine nucleotide. Thus, this technique affords a foundation for the resolution of oxidation-reduction states in two and three dimensions.", "contents": "Oxidation-reduction ratio studies of mitochondria in freeze-trapped samples. NADH and flavoprotein fluorescence signals. The recording of oxidation-reduction-related fluorescence signals of oxidized flavoprotein (Fp) and reduced pyridine nucleotide (PN) from isolated mitochondria at temperatures below -80 degrees C can be accompanished with a high degree of accuracy and a wide dynamic range. The specific low temperature enhancement of the fluorescence signals due to increased quantum yield and to multiple scattering affords increased accuracy and less interference due to screening pigments such as hemoglobin and myoglobin. Since the metabolic processes are arrested and the recording speed can be greatly diminished, the technique can operate with a much smaller concentration of mitochondria than is needed at room temperature, and the method is suitable for localized oxidation-reduction measurements. The Fp and PN signals originate from the mitochondrial matrix space in which they represent the major fluorochromes. Since Fp and PN are near oxidation-reduction equilibrium, the ratio of the two fluorescence intensities, suitably normalized, approximates the oxidation-reduction ratio of oxidized flavoprotein/reduced pyridine nucleotide. Thus, this technique affords a foundation for the resolution of oxidation-reduction states in two and three dimensions."}
{"id": "PMID:220261", "title": "Purification of murine oncornaviral phosphoproteins using alkyl agarose derivatives..", "content": "Methods for the purification of both murine mammary tumor (type B) and murine leukemia (type C) oncornaviral phosphoproteins are described, in which chromatography on alkyl-agarose derivatives is used as the primary fractionation step. Gel filtration or ion exchange chromatography on phosphocellulose was the only subsequent step required for the purification of the type B and type C viral proteins, respectively. The two-step protocols also resulted in the co-purification of a low molecular weight core protein from each virus. Recoveries of the viral proteins purified by this method, based on per cent contribution of individual polypeptides to total virion proteins, were 70% or greater. Radioimmunocompetition analysis of the purified murine mammary tumor virus major core protein as well as analysis of the RNA binding properties of purified low molecular weight type C virus proteins suggests that neither antigenic reactivity nor specific RNA binding characteristics are altered by the purification protocols. The availability of these procedures should aid studies on the possible function and immunochemical properties of the native murine oncornaviral phosphoproteins and may also be extended to the purification of other oncornaviral proteins.", "contents": "Purification of murine oncornaviral phosphoproteins using alkyl agarose derivatives.. Methods for the purification of both murine mammary tumor (type B) and murine leukemia (type C) oncornaviral phosphoproteins are described, in which chromatography on alkyl-agarose derivatives is used as the primary fractionation step. Gel filtration or ion exchange chromatography on phosphocellulose was the only subsequent step required for the purification of the type B and type C viral proteins, respectively. The two-step protocols also resulted in the co-purification of a low molecular weight core protein from each virus. Recoveries of the viral proteins purified by this method, based on per cent contribution of individual polypeptides to total virion proteins, were 70% or greater. Radioimmunocompetition analysis of the purified murine mammary tumor virus major core protein as well as analysis of the RNA binding properties of purified low molecular weight type C virus proteins suggests that neither antigenic reactivity nor specific RNA binding characteristics are altered by the purification protocols. The availability of these procedures should aid studies on the possible function and immunochemical properties of the native murine oncornaviral phosphoproteins and may also be extended to the purification of other oncornaviral proteins."}
{"id": "PMID:220262", "title": "The spatial relationships and structure of the binuclear iron-sulfur clusters in succinate dehydrogenase.", "content": "Two binuclear iron-sulfur clusters (designated S-1 and S-2) are present in succinate dehydrogenase in approximately equal concentration to that of flavin. The large difference in their midpoint potentials (0 and -400 mV, respectively, in the soluble enzyme) permits the acquisition of individual electron paramagnetic resonance spectra characterized by nearly identical rhombic g tensors (gz = 2.025, gy = 1.93, gx = 1.905). Spin-coupling between the two centers is manifested by broadening and splitting of spectra of reconstitutively active and inactive succinate dehydrogenase, respectively, as the temperature is lowered; relief of power saturation of Center S-1 spectra on reduction of Center S 2; and observation of half-field (\"delta ms = 2\") signals in the dithionite-reduced enzyme. Saturation behavior of fully reduced dehydrogenase is consistent with the presence of S-1 and S-2 at equivalent concentrations/molecule. Simulation of the spin-coupled spectra, assuming dipolar interaction, provides information on molecular structure. Electron paramagnetic resonance spectra of the enzyme in 80% dimethylsulfoxide are nearly identical to the characteristic binuclear spectra obtained with adrenodoxin. These data provide additional evidence for binuclear structure of both Center S-1 and S-2. The extremely fast relaxation of Center S-2 at low temperatures would imply either an anomalously small value of J or an alternative relaxation mechanism, possibly due to the coupling between S-1 and S-2.", "contents": "The spatial relationships and structure of the binuclear iron-sulfur clusters in succinate dehydrogenase. Two binuclear iron-sulfur clusters (designated S-1 and S-2) are present in succinate dehydrogenase in approximately equal concentration to that of flavin. The large difference in their midpoint potentials (0 and -400 mV, respectively, in the soluble enzyme) permits the acquisition of individual electron paramagnetic resonance spectra characterized by nearly identical rhombic g tensors (gz = 2.025, gy = 1.93, gx = 1.905). Spin-coupling between the two centers is manifested by broadening and splitting of spectra of reconstitutively active and inactive succinate dehydrogenase, respectively, as the temperature is lowered; relief of power saturation of Center S-1 spectra on reduction of Center S 2; and observation of half-field (\"delta ms = 2\") signals in the dithionite-reduced enzyme. Saturation behavior of fully reduced dehydrogenase is consistent with the presence of S-1 and S-2 at equivalent concentrations/molecule. Simulation of the spin-coupled spectra, assuming dipolar interaction, provides information on molecular structure. Electron paramagnetic resonance spectra of the enzyme in 80% dimethylsulfoxide are nearly identical to the characteristic binuclear spectra obtained with adrenodoxin. These data provide additional evidence for binuclear structure of both Center S-1 and S-2. The extremely fast relaxation of Center S-2 at low temperatures would imply either an anomalously small value of J or an alternative relaxation mechanism, possibly due to the coupling between S-1 and S-2."}
{"id": "PMID:220264", "title": "A rapid method for detecting and mapping homology between heterologous DNAs. Evaluation of polyomavirus genomes.", "content": "A new approach for evaluating homologous sequences among related DNAs is presented. Conventional filter hybridization techniques are employed at 35 degrees C in a range of formamide concentrations in order to perform annealings at effective temperatures as low as Tm -50 degrees C which permits the detection of regions of homology with as much as 33% base mismatch. Under such nonstringent conditions, high levels of specific annealing can be obtained at plateau levels. In combination with the Southern \"blotting\" technique (1975), this approach can be used to perform biochemical heteroduplex melting experiments. The homology among the genomes of the murine polyoma virus (Py), the simian virus 40 (SV40), and the human papovavirus BK was evaluated using this new methodology.", "contents": "A rapid method for detecting and mapping homology between heterologous DNAs. Evaluation of polyomavirus genomes. A new approach for evaluating homologous sequences among related DNAs is presented. Conventional filter hybridization techniques are employed at 35 degrees C in a range of formamide concentrations in order to perform annealings at effective temperatures as low as Tm -50 degrees C which permits the detection of regions of homology with as much as 33% base mismatch. Under such nonstringent conditions, high levels of specific annealing can be obtained at plateau levels. In combination with the Southern \"blotting\" technique (1975), this approach can be used to perform biochemical heteroduplex melting experiments. The homology among the genomes of the murine polyoma virus (Py), the simian virus 40 (SV40), and the human papovavirus BK was evaluated using this new methodology."}
{"id": "PMID:220266", "title": "Carcinogenic effects in the Syrian golden hamster of N-methyl-N-formylhydrazine of the false morel mushroom Gyromitra esculenta.", "content": "N-Methyl-N-formylhydrazine (MFH) was administered in drinking water as a 0.0078% solution to randomly bred Syrian golden hamsters for life beginning at 6 weeks of age. The treatment gave rise to benign and malignant liver cell tumors, malignant histiocytomas and tumors of the gall bladder and bile ducts. The tumor incidence in these four treated tissues was 43, 34, 11,8%, while in untreated controls it was 0, 0, 0, 0%, respectively. Histopathologically, tumors were classified as benign hepatomas, liver cell carcinomas, malignant histiocytomas, adenomas and adenocarcinomas of the gall bladder, cholangiomas, and cholangiocarcinomas.", "contents": "Carcinogenic effects in the Syrian golden hamster of N-methyl-N-formylhydrazine of the false morel mushroom Gyromitra esculenta. N-Methyl-N-formylhydrazine (MFH) was administered in drinking water as a 0.0078% solution to randomly bred Syrian golden hamsters for life beginning at 6 weeks of age. The treatment gave rise to benign and malignant liver cell tumors, malignant histiocytomas and tumors of the gall bladder and bile ducts. The tumor incidence in these four treated tissues was 43, 34, 11,8%, while in untreated controls it was 0, 0, 0, 0%, respectively. Histopathologically, tumors were classified as benign hepatomas, liver cell carcinomas, malignant histiocytomas, adenomas and adenocarcinomas of the gall bladder, cholangiomas, and cholangiocarcinomas."}
{"id": "PMID:220267", "title": "Karyotypic variations in human meningioma cell cultures under different in vitro conditions.", "content": "Examined were how changes of the culture medium, cultivating procedure and cultivating time will influence numerical representation of different karyotypes in a total of 27 cell cultures of meningiomas with two or more cytogenetically distinguishable cell lines. It could be shown that in medium I (80% Mc Coy 5 A, 20% fetal calf serum) more cell lines with a higher degree of hypodipoidy occurred than in medium II (50% TC 199, 40% bovine amniotic fluid, 10% calf serum). The number of cells with normal karyotype was higher in cultures which were grown from trypsinized biopsy material in stationary flasks when compared to particle cultures in roller tubes. Cells with a normal karyotype also increased after 1--6 subcultures. By demonstration of SV 40 tumor antigen it could be shown in two cultures that these normal mitoses derived from tumoral and not from stromal tissue.", "contents": "Karyotypic variations in human meningioma cell cultures under different in vitro conditions. Examined were how changes of the culture medium, cultivating procedure and cultivating time will influence numerical representation of different karyotypes in a total of 27 cell cultures of meningiomas with two or more cytogenetically distinguishable cell lines. It could be shown that in medium I (80% Mc Coy 5 A, 20% fetal calf serum) more cell lines with a higher degree of hypodipoidy occurred than in medium II (50% TC 199, 40% bovine amniotic fluid, 10% calf serum). The number of cells with normal karyotype was higher in cultures which were grown from trypsinized biopsy material in stationary flasks when compared to particle cultures in roller tubes. Cells with a normal karyotype also increased after 1--6 subcultures. By demonstration of SV 40 tumor antigen it could be shown in two cultures that these normal mitoses derived from tumoral and not from stromal tissue."}
{"id": "PMID:220268", "title": "Distribution of T- and B-cells and of immunoglobulin-producing cells in tumor tissue of patients with nasopharyngeal carcinoma.", "content": "Various subtypes of 17 European nasopharyngeal carcinomas are examined by immunocytological and immunohistological methods. The T- and B-Cells in the inflammatory infiltrate are determined quantitatively and correlated with the amount and type of intracellular immunoglobulin. This data is compared with peripheral T-Cell values and the serum anti Epstein-Barr virus (EBV) titers, and finally with the tumor type and stage. Three of the 17 patients had marked local immunoglobulin producing cells, 8 only moderate, and 6 had nearly none. The intracellular immunoglobulin was primarily IgG/kappa, and no significant increase of IgA producing cells was observed as suggested by others. No clearcut correlation was found between local T- and B-Cell infiltrates and the tumor type, stage of disease, or anti EBV titers in the patients' serum. The possible implication of this data is discussed.", "contents": "Distribution of T- and B-cells and of immunoglobulin-producing cells in tumor tissue of patients with nasopharyngeal carcinoma. Various subtypes of 17 European nasopharyngeal carcinomas are examined by immunocytological and immunohistological methods. The T- and B-Cells in the inflammatory infiltrate are determined quantitatively and correlated with the amount and type of intracellular immunoglobulin. This data is compared with peripheral T-Cell values and the serum anti Epstein-Barr virus (EBV) titers, and finally with the tumor type and stage. Three of the 17 patients had marked local immunoglobulin producing cells, 8 only moderate, and 6 had nearly none. The intracellular immunoglobulin was primarily IgG/kappa, and no significant increase of IgA producing cells was observed as suggested by others. No clearcut correlation was found between local T- and B-Cell infiltrates and the tumor type, stage of disease, or anti EBV titers in the patients' serum. The possible implication of this data is discussed."}
{"id": "PMID:220269", "title": "Karyology and tumorigenicity of a simian virus 40-transformed Chinese hamster cell clone.", "content": "A pseudodiploid clone of chinese hamster cells tranformed in vitro with Simian virus 40 (SV40) was isolated from soft agar and injected into nude mice through three successive passages with a short in vitro cultivation between each animal inoculation. the original clone and the three subsequent tumor populations were characterized in regard to SV40 T antigen staining, modal chromosome number, and Giemsa-banded karyotype. All tumor cell lines maintained the pseudodiploid mode, as well as the positive sv40 t antigen staining. Nonrandom chromosomal changes included loss of one of the X chromosomes, additions of abnormal variants of chromosomes No. 1 and No. 2, the appearance of unidentified marker chromosomes, and the loss of autosomes No. 5, No. 6, and No. 11. The deletion of one of the X chromosomes occurred with about the same frequency in all cell lines. Additions of abnormal chromosomes No. 1 and No. 2 tended to recur more often in the tumor cell lines than in the original clone. the appearance of marker chromosomes, as well as the loss of autosomes No. 5, No. 6, and No. 11 demonstrated a correlation with tumorigenicity. Yet, the three successive passages of the cells through the animal did not select for a tumor population with a single, homogeneous karyotype.", "contents": "Karyology and tumorigenicity of a simian virus 40-transformed Chinese hamster cell clone. A pseudodiploid clone of chinese hamster cells tranformed in vitro with Simian virus 40 (SV40) was isolated from soft agar and injected into nude mice through three successive passages with a short in vitro cultivation between each animal inoculation. the original clone and the three subsequent tumor populations were characterized in regard to SV40 T antigen staining, modal chromosome number, and Giemsa-banded karyotype. All tumor cell lines maintained the pseudodiploid mode, as well as the positive sv40 t antigen staining. Nonrandom chromosomal changes included loss of one of the X chromosomes, additions of abnormal variants of chromosomes No. 1 and No. 2, the appearance of unidentified marker chromosomes, and the loss of autosomes No. 5, No. 6, and No. 11. The deletion of one of the X chromosomes occurred with about the same frequency in all cell lines. Additions of abnormal chromosomes No. 1 and No. 2 tended to recur more often in the tumor cell lines than in the original clone. the appearance of marker chromosomes, as well as the loss of autosomes No. 5, No. 6, and No. 11 demonstrated a correlation with tumorigenicity. Yet, the three successive passages of the cells through the animal did not select for a tumor population with a single, homogeneous karyotype."}
{"id": "PMID:220270", "title": "Biochemical genetic analysis of pyrimidine biosynthesis in mammalian cells. II. Isolation and characterization of a mutant of Chinese hamster ovary cells with defective dihydroorotate dehydrogenase (E.C. 1.3.3.1) activity.", "content": "A mutant (A204) of Chinese hamster ovary cells (CHO-K1), which is deficient in dihydroorotate (DHO) dehydrogenase (E.C. 1.3,3.1) activity, has been isolated by a replica plating procedure. The mutant does not show a requirement for exogenously added pyrimidines. Examination of intact cells shows that the mutant accumulates a large amount of carbamyl aspartate and is markedly but not totally deficient in biosynthesis of orotate from earlier precursors of pyrimidine biosynthesis, including aspartate and dihydroorotic acid, when compared to wild-type cells. Analysis of cell-free extracts of mutant and wild-type cells shows that the mutant is deficient in DHO dehydrogenase activity, possessing ca. 5% of the wild-type activity. this evidence leads to the conclusion that this mutant, A204, is in fact partially deficient in DHO dehydrogenase, and that in these cells it is this enzyme which carries out the fourth step of de novo pyrimidine biosynthesis.", "contents": "Biochemical genetic analysis of pyrimidine biosynthesis in mammalian cells. II. Isolation and characterization of a mutant of Chinese hamster ovary cells with defective dihydroorotate dehydrogenase (E.C. 1.3.3.1) activity. A mutant (A204) of Chinese hamster ovary cells (CHO-K1), which is deficient in dihydroorotate (DHO) dehydrogenase (E.C. 1.3,3.1) activity, has been isolated by a replica plating procedure. The mutant does not show a requirement for exogenously added pyrimidines. Examination of intact cells shows that the mutant accumulates a large amount of carbamyl aspartate and is markedly but not totally deficient in biosynthesis of orotate from earlier precursors of pyrimidine biosynthesis, including aspartate and dihydroorotic acid, when compared to wild-type cells. Analysis of cell-free extracts of mutant and wild-type cells shows that the mutant is deficient in DHO dehydrogenase activity, possessing ca. 5% of the wild-type activity. this evidence leads to the conclusion that this mutant, A204, is in fact partially deficient in DHO dehydrogenase, and that in these cells it is this enzyme which carries out the fourth step of de novo pyrimidine biosynthesis."}
{"id": "PMID:220271", "title": "Cholera toxin stimulates division of 3T3 cells.", "content": "Cholera toxin was used in an attempt to inhibit epidermal growth factor stimulated 3T3 cell division. Instead, cholera toxin alone at low concentrations (10(-10) M), was able to stimulate cell division and could augment EGF stimulated cell division. The mitogenic effect of cholera toxin can occur despite a dramatic increase in the intracellular levels of cAMP in 3T3 cells. Cholera toxin stimulated mitogenesis could not be mimicked by choleragenoid, the binding but inactive subunit of cholera toxin, or by other agents which elevate cAMP levels in 3T3 cells.", "contents": "Cholera toxin stimulates division of 3T3 cells. Cholera toxin was used in an attempt to inhibit epidermal growth factor stimulated 3T3 cell division. Instead, cholera toxin alone at low concentrations (10(-10) M), was able to stimulate cell division and could augment EGF stimulated cell division. The mitogenic effect of cholera toxin can occur despite a dramatic increase in the intracellular levels of cAMP in 3T3 cells. Cholera toxin stimulated mitogenesis could not be mimicked by choleragenoid, the binding but inactive subunit of cholera toxin, or by other agents which elevate cAMP levels in 3T3 cells."}
{"id": "PMID:220272", "title": "Effects of angiotensin II and angiotensin II antagonist saralasin on cell growth and renin in 3T3 and SV3T3 cells.", "content": "Components of the renin-angiotensin system were studied in established cell culture lines of 3T3 and SV3T3 mouse fibroblasts. The renin content in 3T3 cells was significantly higher than in virus-transformed SV3T3 cells. With time after infection, renin decreased in Simian virus 40 transformed cells, while it increased steadily in mock-infected 3T3 cells. In contrast to renin, angiotensinase activity was higher in SV3T3 cells. Angiotensin II stimulated cell proliferation in 3T3 mouse fibroblasts and decreased their renin content in a dose-related manner. In contrast, saralasin, an angiotensin receptor antagonist, inhibited cell growth in 3T3 and SV3T3 cells and caused an increase of cellular renin concentration. The angiotensin fragments angiotensin (2-8) heptapeptide and angiotensin (4-8) pentapeptide had no effect on cell growth. A significant negative correlation was found between cell proliferation and renin levels in 3T3 and SV3T3 cells irrespective of the treatment. Our results indicate (1) that angiotensin II may be involved in cell growth regulation, (2) that a negative feedback exist between angiotensin II added and intracellular renin content, and (3) that virus infection causes a decrease in intracellular renin synthesis, while non-specific angiotensinase activity is increased under this condition.", "contents": "Effects of angiotensin II and angiotensin II antagonist saralasin on cell growth and renin in 3T3 and SV3T3 cells. Components of the renin-angiotensin system were studied in established cell culture lines of 3T3 and SV3T3 mouse fibroblasts. The renin content in 3T3 cells was significantly higher than in virus-transformed SV3T3 cells. With time after infection, renin decreased in Simian virus 40 transformed cells, while it increased steadily in mock-infected 3T3 cells. In contrast to renin, angiotensinase activity was higher in SV3T3 cells. Angiotensin II stimulated cell proliferation in 3T3 mouse fibroblasts and decreased their renin content in a dose-related manner. In contrast, saralasin, an angiotensin receptor antagonist, inhibited cell growth in 3T3 and SV3T3 cells and caused an increase of cellular renin concentration. The angiotensin fragments angiotensin (2-8) heptapeptide and angiotensin (4-8) pentapeptide had no effect on cell growth. A significant negative correlation was found between cell proliferation and renin levels in 3T3 and SV3T3 cells irrespective of the treatment. Our results indicate (1) that angiotensin II may be involved in cell growth regulation, (2) that a negative feedback exist between angiotensin II added and intracellular renin content, and (3) that virus infection causes a decrease in intracellular renin synthesis, while non-specific angiotensinase activity is increased under this condition."}
{"id": "PMID:220273", "title": "Evidence suggesting that a cyclic AMP-dependent protein kinase is a positive regulator of proliferation in Cloudman S91 melanoma cells.", "content": "Wild-type Cloudman S91 melanoma cells have a retarded rate of division when agents which raise cyclic AMP levels such as melanotropin, protaglandin E1, or cholera toxin are supplemented to the culture medium. A mutant cell line was isolated which had the opposite response, i.e., the mutant grew very slowly unless agents which raised cyclic AMP levels were present (Pawelek et al., '75a). In this report evidence is presented indicating that the molecular basis for the mutant phenotype resides in the major cyclic AMP-dependent protein kinase found in the cells. The mutant kinase had increased thermolability and an elevated activation constant for cyclic AMP over the corresponding wild-type kinase. It is proposed that the elevated requirement for cyclic AMP for the proliferation of cAdep cells is related to the elevated activation constant of the kinase, suggesting that the kinase is a positive regulator of proliferation in Cloudman S91 cells.", "contents": "Evidence suggesting that a cyclic AMP-dependent protein kinase is a positive regulator of proliferation in Cloudman S91 melanoma cells. Wild-type Cloudman S91 melanoma cells have a retarded rate of division when agents which raise cyclic AMP levels such as melanotropin, protaglandin E1, or cholera toxin are supplemented to the culture medium. A mutant cell line was isolated which had the opposite response, i.e., the mutant grew very slowly unless agents which raised cyclic AMP levels were present (Pawelek et al., '75a). In this report evidence is presented indicating that the molecular basis for the mutant phenotype resides in the major cyclic AMP-dependent protein kinase found in the cells. The mutant kinase had increased thermolability and an elevated activation constant for cyclic AMP over the corresponding wild-type kinase. It is proposed that the elevated requirement for cyclic AMP for the proliferation of cAdep cells is related to the elevated activation constant of the kinase, suggesting that the kinase is a positive regulator of proliferation in Cloudman S91 cells."}
{"id": "PMID:220276", "title": "Postmenopausal virilization due to ovarian stromal hyperthecosis.", "content": "A 53-year-old woman presented with hirsutism of long duration and virilization of recent onset. She was gravida 12 para 9. The 17-ketosteroids were normal, gonadotropins were in the post-menopausal range, and the serum testosterone was in the male range. After bilateral oophorectomy, the testosterone became normal. Ovarian pathology revealed stromal hyperthecosis.", "contents": "Postmenopausal virilization due to ovarian stromal hyperthecosis. A 53-year-old woman presented with hirsutism of long duration and virilization of recent onset. She was gravida 12 para 9. The 17-ketosteroids were normal, gonadotropins were in the post-menopausal range, and the serum testosterone was in the male range. After bilateral oophorectomy, the testosterone became normal. Ovarian pathology revealed stromal hyperthecosis."}
{"id": "PMID:220278", "title": "Cyproheptadine treatment of Nelson's syndrome: restoration of plasma ACTH circadian periodicity and reversal of response to TRF.", "content": "Administration of cyproheptadine for four months to a patient with Nelson's Syndrome was associated with evidence of skin lightening, decreased plasma ACTH concentrations, return of a normal circadian periodicity of plasma ACTH concentrations, and lack of responsiveness of plasma ACTH concentrations to TRF administration, in contrast to the response seen in the untreated state.", "contents": "Cyproheptadine treatment of Nelson's syndrome: restoration of plasma ACTH circadian periodicity and reversal of response to TRF. Administration of cyproheptadine for four months to a patient with Nelson's Syndrome was associated with evidence of skin lightening, decreased plasma ACTH concentrations, return of a normal circadian periodicity of plasma ACTH concentrations, and lack of responsiveness of plasma ACTH concentrations to TRF administration, in contrast to the response seen in the untreated state."}
{"id": "PMID:220279", "title": "Production of diglyceride from phosphatidylinositol in activated human platelets.", "content": "Human platelets generate diglyceride within 5 s of exposure to thrombin. Production of diglyceride is transient. 15 s after the addition of thrombin, the levels of diglyceride have increased up to 30-fold, but decrease thereafter. Prior incubation of platelets with 2 mM dibutyryl cyclic AMP prevents both the generation of diglyceride and the secretion of serotonin. Acetylsalicylic acid (100 microgram/ml), which completely inhibits prostaglandin endoperoxide synthesis, does not block diglyceride production and serotonin secretion induced by thrombin. Based on studies examining the incorporation of [3H]arachidonic acid into diglyceride of prelabeled platelets exposed to thrombin, it is concluded that neither phosphatidic acid nor triglyceride is the source of the diglyceride. Phosphatidylinositol appears to be the most likely source, both because its loss of radiolabel is sizable and rapid enough to account for the appearance of radiolabel in diglyceride, and because a phosphatidylinositol-specific phosphodiesterase, described in this report, exists in platelets. The phosphatidylinositol-phosphodiesterase, which produces diglyceride and inositol phosphate, requires Ca+2 and shows optimal activity at pH 7. The enzyme does not act upon phosphatidylcholine, phosphatidylethanolamine, or phosphatidylserine.", "contents": "Production of diglyceride from phosphatidylinositol in activated human platelets. Human platelets generate diglyceride within 5 s of exposure to thrombin. Production of diglyceride is transient. 15 s after the addition of thrombin, the levels of diglyceride have increased up to 30-fold, but decrease thereafter. Prior incubation of platelets with 2 mM dibutyryl cyclic AMP prevents both the generation of diglyceride and the secretion of serotonin. Acetylsalicylic acid (100 microgram/ml), which completely inhibits prostaglandin endoperoxide synthesis, does not block diglyceride production and serotonin secretion induced by thrombin. Based on studies examining the incorporation of [3H]arachidonic acid into diglyceride of prelabeled platelets exposed to thrombin, it is concluded that neither phosphatidic acid nor triglyceride is the source of the diglyceride. Phosphatidylinositol appears to be the most likely source, both because its loss of radiolabel is sizable and rapid enough to account for the appearance of radiolabel in diglyceride, and because a phosphatidylinositol-specific phosphodiesterase, described in this report, exists in platelets. The phosphatidylinositol-phosphodiesterase, which produces diglyceride and inositol phosphate, requires Ca+2 and shows optimal activity at pH 7. The enzyme does not act upon phosphatidylcholine, phosphatidylethanolamine, or phosphatidylserine."}
{"id": "PMID:220280", "title": "Fluoride-mediated activation of the respiratory burst in human neutrophils. A reversible process.", "content": "Fluoride ion (F-) is an effective activator of the respiratory burst in neutrophils, as indicated by its ability to induce O2- production by these cells. Other halide ions did not activate the burst, Cl-, in particular appeared to antagonize the effect of F- on O2- production. F- stimulated O2- production showed a requirement for Ca++, but was independent of other exogenous cations. Neither phagocytosis nor degranulation were necessary for respiratory burst activation by F-. The effect of F- on the respiratory burst was reversible. Washing the cells after treatment with F-, while they were still producing large amounts of O2-, returned them to the resting state. They could then be stimulated again to produce O2- in amounts equivalent to those originally produced. Our experiments indicated that restimulation did not represent the activation of a population of cells that had not been activated during the initial exposure to F-, nor did it represent serial activation of different subpopulation of the O2- forming enzyme molecules present in a given cell. Rather, our data suggest that the entire population of O2- forming enzyme molecules was activated in a reversible fashion by F-.", "contents": "Fluoride-mediated activation of the respiratory burst in human neutrophils. A reversible process. Fluoride ion (F-) is an effective activator of the respiratory burst in neutrophils, as indicated by its ability to induce O2- production by these cells. Other halide ions did not activate the burst, Cl-, in particular appeared to antagonize the effect of F- on O2- production. F- stimulated O2- production showed a requirement for Ca++, but was independent of other exogenous cations. Neither phagocytosis nor degranulation were necessary for respiratory burst activation by F-. The effect of F- on the respiratory burst was reversible. Washing the cells after treatment with F-, while they were still producing large amounts of O2-, returned them to the resting state. They could then be stimulated again to produce O2- in amounts equivalent to those originally produced. Our experiments indicated that restimulation did not represent the activation of a population of cells that had not been activated during the initial exposure to F-, nor did it represent serial activation of different subpopulation of the O2- forming enzyme molecules present in a given cell. Rather, our data suggest that the entire population of O2- forming enzyme molecules was activated in a reversible fashion by F-."}
{"id": "PMID:220281", "title": "Ricinoleic acid stimulation of active anion secretion in colonic mucosa of the rat.", "content": "Perfusion of the colon with ricinoleic acid produces fluid and electrolyte accumulation. The mechanism of these changes in water and electrolyte movement is uknown. These studies were designed to determine whether ricinoleic acid effects active ion transport across isolated rat colonic mucosa. 0.5 mM Na ricinoleate produced significant increases in potential difference (3.8 +/- 0.5 mV) and short-circuit current (Isc) (99.2 +/- 10.1 muA/cm2). The increases in Isc produced by Na ricinoleate were inhibited by both removal of bicarbonate and chloride and by the presence of theophylline. The hydroxy fatty acid also resulted in a significant decrease in net Na absorption from 4.7 +/- 0.8 to 0.1 +/- 0.7 mueq/h cm2 and reversed net Cl transport from absorption (+ 4.5 +/- 0.9) to secretion (-2.2 +/- mueq/h cm2). In parallel studies 0.5 mM Na ricinoleate increased mucosal cyclic AMP content by 58%. The concentrations of Na ricinoleate required to produce detectable and maximal increases in both Isc and cyclic AMP were the same. These results provide evidence in support of the concept that hydroxy fatty acid-induced fluid and electrolyte accumulation is driven by an active ion secretory process.", "contents": "Ricinoleic acid stimulation of active anion secretion in colonic mucosa of the rat. Perfusion of the colon with ricinoleic acid produces fluid and electrolyte accumulation. The mechanism of these changes in water and electrolyte movement is uknown. These studies were designed to determine whether ricinoleic acid effects active ion transport across isolated rat colonic mucosa. 0.5 mM Na ricinoleate produced significant increases in potential difference (3.8 +/- 0.5 mV) and short-circuit current (Isc) (99.2 +/- 10.1 muA/cm2). The increases in Isc produced by Na ricinoleate were inhibited by both removal of bicarbonate and chloride and by the presence of theophylline. The hydroxy fatty acid also resulted in a significant decrease in net Na absorption from 4.7 +/- 0.8 to 0.1 +/- 0.7 mueq/h cm2 and reversed net Cl transport from absorption (+ 4.5 +/- 0.9) to secretion (-2.2 +/- mueq/h cm2). In parallel studies 0.5 mM Na ricinoleate increased mucosal cyclic AMP content by 58%. The concentrations of Na ricinoleate required to produce detectable and maximal increases in both Isc and cyclic AMP were the same. These results provide evidence in support of the concept that hydroxy fatty acid-induced fluid and electrolyte accumulation is driven by an active ion secretory process."}
{"id": "PMID:220282", "title": "Glucocorticoid receptors and actions in subpopulations of cultured rat bone cells. Mechanism of dexamethasone potentiation of parathyroid hormone-stimulated cyclic AMP production.", "content": "We have previously shown that bone cells possess glucocorticoid receptors and that, in addition to being inhibitory to cell growth, glucocorticoid treatment potentiates the ability of parathyroid hormone (PTH) to stimulate cyclic AMP (cAMP) formation. This study extends those observations to specific subpopulations of bone cells and explores the mechanism of the cAMP augmentation. Subpopulations of cultured bone cells derived from 20-d-old fetal rat calvaria were enriched for \"osteoblast-like\" (OB) and \"osteoclast-like\" (OC) cells by sequential collagenase digestion. OC cells released during the first 30 min of collagenase digestion were characterized by low alkaline phosphatase activity, a cAMP response to salmon calcitonin (CT), but only a small cAMP response to bovine PTH. In contrast, OB cells released between 30 and 120 min of collagenase digestion, possessed high alkaline phosphatase activity, responded with a large cAMP rise to PTH, but exhibited no response to CT. Glucocorticoid receptors, with similar properties, were demonstrated in both populations (K(d) congruent with 5 nM, N(maximum) congruent with 400 fmol/mg cytosol protein). Dexamethasone equivalently inhibited cell growth and alkaline phosphatase activity in both populations. Dexamethasone potentiation of cAMP generation occurred after PTH but not CT stimulation. A greater enhancement of cAMP generation observed in OB cells appears to result from two glucocorticoid actions: (a) stimulation of adenylate cyclase and (b) inhibition of phosphodiesterase. Only the latter mechanism was found in OC cells. Dexamethasone-treated cells showed an increase in both sensitivity and maximal response of cAMP to PTH. The possible relationship of these actions to the mechanism of glucocorticoid-induced osteopenia is discussed.", "contents": "Glucocorticoid receptors and actions in subpopulations of cultured rat bone cells. Mechanism of dexamethasone potentiation of parathyroid hormone-stimulated cyclic AMP production. We have previously shown that bone cells possess glucocorticoid receptors and that, in addition to being inhibitory to cell growth, glucocorticoid treatment potentiates the ability of parathyroid hormone (PTH) to stimulate cyclic AMP (cAMP) formation. This study extends those observations to specific subpopulations of bone cells and explores the mechanism of the cAMP augmentation. Subpopulations of cultured bone cells derived from 20-d-old fetal rat calvaria were enriched for \"osteoblast-like\" (OB) and \"osteoclast-like\" (OC) cells by sequential collagenase digestion. OC cells released during the first 30 min of collagenase digestion were characterized by low alkaline phosphatase activity, a cAMP response to salmon calcitonin (CT), but only a small cAMP response to bovine PTH. In contrast, OB cells released between 30 and 120 min of collagenase digestion, possessed high alkaline phosphatase activity, responded with a large cAMP rise to PTH, but exhibited no response to CT. Glucocorticoid receptors, with similar properties, were demonstrated in both populations (K(d) congruent with 5 nM, N(maximum) congruent with 400 fmol/mg cytosol protein). Dexamethasone equivalently inhibited cell growth and alkaline phosphatase activity in both populations. Dexamethasone potentiation of cAMP generation occurred after PTH but not CT stimulation. A greater enhancement of cAMP generation observed in OB cells appears to result from two glucocorticoid actions: (a) stimulation of adenylate cyclase and (b) inhibition of phosphodiesterase. Only the latter mechanism was found in OC cells. Dexamethasone-treated cells showed an increase in both sensitivity and maximal response of cAMP to PTH. The possible relationship of these actions to the mechanism of glucocorticoid-induced osteopenia is discussed."}
{"id": "PMID:220283", "title": "In vitro suppression of serum elastase-inhibitory capacity by reactive oxygen species generated by phagocytosing polymorphonuclear leukocytes.", "content": "Human polymorphonuclear leukocytes (PMN) phagocytosing opsonized antigen-antibody complexes, produce dialyzable species of activated oxygen which are capable of partially suppressing the elastase-inhibiting capacity (EIC) of whole human serum or purified human alpha1-proteinase inhibitor. Serum EIC was partially protially protected by superoxide dismutase, catalase, or mannitol, suggesting that hydroxyl radical, formed by interaction of superoxide radical and hydrogen peroxide, might be responsible for this effect. NaN3 also partly protected EIC, implicating myeloperoxidase-mediated reactions as well. An artificial superoxide rradical-generating system, involving xanthine and xanthine-oxidase, could be substituted for phagocytosing PMN with resultant EIC suppression. These results are consistent with previous demonstrations of the release of potent oxidants by stimulated PMN, as well as earlier studies from our laboratory showing sensitivity of alpha1-proteinase inhibitor to inactivation by oxidants. Oxidative inactivation of proteinase inhibitors in the microenvironment of PMN accumulating at sites of inflammation may allow proteases released from these cells to more readily damage adjacent connective tissue structures.", "contents": "In vitro suppression of serum elastase-inhibitory capacity by reactive oxygen species generated by phagocytosing polymorphonuclear leukocytes. Human polymorphonuclear leukocytes (PMN) phagocytosing opsonized antigen-antibody complexes, produce dialyzable species of activated oxygen which are capable of partially suppressing the elastase-inhibiting capacity (EIC) of whole human serum or purified human alpha1-proteinase inhibitor. Serum EIC was partially protially protected by superoxide dismutase, catalase, or mannitol, suggesting that hydroxyl radical, formed by interaction of superoxide radical and hydrogen peroxide, might be responsible for this effect. NaN3 also partly protected EIC, implicating myeloperoxidase-mediated reactions as well. An artificial superoxide rradical-generating system, involving xanthine and xanthine-oxidase, could be substituted for phagocytosing PMN with resultant EIC suppression. These results are consistent with previous demonstrations of the release of potent oxidants by stimulated PMN, as well as earlier studies from our laboratory showing sensitivity of alpha1-proteinase inhibitor to inactivation by oxidants. Oxidative inactivation of proteinase inhibitors in the microenvironment of PMN accumulating at sites of inflammation may allow proteases released from these cells to more readily damage adjacent connective tissue structures."}
{"id": "PMID:220284", "title": "Portal vein invasion demonstrated by ultrasound.", "content": "Two patients evaluated by ultrasound for abdominal masses were found to have thrombus within their central portal veins. Their cases are presented with angiographic correlation. Both are proven cases of hepatocellular carcinoma. The importance of evaluation of the portal vein in patients with liver neoplasms is discussed.", "contents": "Portal vein invasion demonstrated by ultrasound. Two patients evaluated by ultrasound for abdominal masses were found to have thrombus within their central portal veins. Their cases are presented with angiographic correlation. Both are proven cases of hepatocellular carcinoma. The importance of evaluation of the portal vein in patients with liver neoplasms is discussed."}
{"id": "PMID:220285", "title": "Comparison of enzyme-linked immunosorbent assay (ELISA) technique and complement-fixation test for estimation of cytomegalovirus IgG antibody.", "content": "The ELISA technique has been found to be reliable for the detection and titration of cytomegalovirus-specific IgG antibody in serum. It is about six times more sensitive than the CF test although some discrepancies were found between the antibody titres determined by the two methods.", "contents": "Comparison of enzyme-linked immunosorbent assay (ELISA) technique and complement-fixation test for estimation of cytomegalovirus IgG antibody. The ELISA technique has been found to be reliable for the detection and titration of cytomegalovirus-specific IgG antibody in serum. It is about six times more sensitive than the CF test although some discrepancies were found between the antibody titres determined by the two methods."}
{"id": "PMID:220286", "title": "Multiple malignant Spiegler tumors with brachydactyly and racket-nails. Light and electron microscopic study.", "content": "Multiple malignant Spiegler tumors were observed on the scalp of a 67-year-old female patient with brachydactyly and racket-nails affecting all fingers of both hands. The occurrence of similar clinical features in the family of the patient is suggestive of a hereditary disorder. The light and electron microscopical findings are described.", "contents": "Multiple malignant Spiegler tumors with brachydactyly and racket-nails. Light and electron microscopic study. Multiple malignant Spiegler tumors were observed on the scalp of a 67-year-old female patient with brachydactyly and racket-nails affecting all fingers of both hands. The occurrence of similar clinical features in the family of the patient is suggestive of a hereditary disorder. The light and electron microscopical findings are described."}
{"id": "PMID:220287", "title": "Potentiation of guanosine 3':5'-monophosphate accumulation in C-6 glial tumor cells.", "content": "C-6 glial tumor cells treated with norepinephrine and sodium azide accumulated cyclic GMP to concentrations approximately 10-fold greater than the sum of the separate responses. Isoproterenol, but not phenylephrine, was an effective substitute for norepinephrine, and the response was blocked by propranolol and sotalol. Nitroprusside, but neither cyanide nor isobutyl-methylxanthine, replaced azide. The potentiation was not affected by removal of CA2+ OR Na+ from the extracellular medium and was not blocked by cocaine. The potentiative accumulation of cyclic GMP in C-6 cells differs from the recently described stimulation by catecholamines of soluble guanylate cyclase of renal cortex. The potentiative phenomenon is compared with the few known instances in which cyclic AMP augments cyclic GMP formation and may be associated with synergistic modifications of cellular functions.", "contents": "Potentiation of guanosine 3':5'-monophosphate accumulation in C-6 glial tumor cells. C-6 glial tumor cells treated with norepinephrine and sodium azide accumulated cyclic GMP to concentrations approximately 10-fold greater than the sum of the separate responses. Isoproterenol, but not phenylephrine, was an effective substitute for norepinephrine, and the response was blocked by propranolol and sotalol. Nitroprusside, but neither cyanide nor isobutyl-methylxanthine, replaced azide. The potentiation was not affected by removal of CA2+ OR Na+ from the extracellular medium and was not blocked by cocaine. The potentiative accumulation of cyclic GMP in C-6 cells differs from the recently described stimulation by catecholamines of soluble guanylate cyclase of renal cortex. The potentiative phenomenon is compared with the few known instances in which cyclic AMP augments cyclic GMP formation and may be associated with synergistic modifications of cellular functions."}
{"id": "PMID:220288", "title": "Effect of sodium fluoride on cyclic AMP production in rat hepatocytes.", "content": "The effect of NaF on cAMP production was studied in hepatocytes isolated from fed and fasted rats. A four-six fold increase in hepatocyte cAMP production was observed in the presence of 10-20 mM NaF in cells isolated from either fed or fasted rats. The maximal stimulation of cAMP production was observed after a 10 min incubation in the presence of 1 mM theophylline. However, as little as 0.05-0.15 mM NaF induced a significant increase in cAMP production. It was also found that NaF would alter the production of glucose in isolated rat hepatocytes. When hepatocytes from fed rats were incubated with 0.05-5 mM NaF there was an increase in amount of glucose released from endogenous sources. Also NaF resulted in a decrease in lactate and pyruvate production. Similarly NaF stimulated glucose production in hepatocytes from fasted rats. The maximal stimulation was observed with about 0.15-0.25 mM NaF. At NaF concentrations greater than 1.5 mM a decrease in glucose production was observed. It is concluded that NaF increases the level of cAMP and alters glucose metabolism in intact hepatocytes.", "contents": "Effect of sodium fluoride on cyclic AMP production in rat hepatocytes. The effect of NaF on cAMP production was studied in hepatocytes isolated from fed and fasted rats. A four-six fold increase in hepatocyte cAMP production was observed in the presence of 10-20 mM NaF in cells isolated from either fed or fasted rats. The maximal stimulation of cAMP production was observed after a 10 min incubation in the presence of 1 mM theophylline. However, as little as 0.05-0.15 mM NaF induced a significant increase in cAMP production. It was also found that NaF would alter the production of glucose in isolated rat hepatocytes. When hepatocytes from fed rats were incubated with 0.05-5 mM NaF there was an increase in amount of glucose released from endogenous sources. Also NaF resulted in a decrease in lactate and pyruvate production. Similarly NaF stimulated glucose production in hepatocytes from fasted rats. The maximal stimulation was observed with about 0.15-0.25 mM NaF. At NaF concentrations greater than 1.5 mM a decrease in glucose production was observed. It is concluded that NaF increases the level of cAMP and alters glucose metabolism in intact hepatocytes."}
{"id": "PMID:220289", "title": "Acute suppression by PGF2 alpha on LH, epinephrine and fluoride stimulation of adenylate cyclase in rat luteal tissue.", "content": "Injection of PGF2 alpha (250 microgram/rat) 15 min prior to isolation of corpora lutea (CL) from PMSG treated immature rats significantly reduced the LH stimulation of adenylate cyclase in CL membranes. The LH stimulation did not return to normal even 24 h after PGF2 alpha injection. A transient decrease in epinephrine and fluoride stimulation of AC was also observed, the response returning to normal 6-12 h after PGF2 alpha treatment. In vitro incubation of whole isolated CL with 0.005 micrometer or higher concentrations of PGF2 alpha markedly reduced the LH and fluoride stimulation of AC in the CL membranes. Exposure of CL to PGF2 alpha for 15 min in vitro reduced the LH and fluoride response. The results are discussed in relation to the suppressive action of PGF2 alpha on LH receptors in CL, and a mechanism is proposed to explain the discrepancy in time relation between our results and the LH receptor studies. The proposed mechanism might also explain the transient decrease in epinephrine and fluoride stimulation of AC.", "contents": "Acute suppression by PGF2 alpha on LH, epinephrine and fluoride stimulation of adenylate cyclase in rat luteal tissue. Injection of PGF2 alpha (250 microgram/rat) 15 min prior to isolation of corpora lutea (CL) from PMSG treated immature rats significantly reduced the LH stimulation of adenylate cyclase in CL membranes. The LH stimulation did not return to normal even 24 h after PGF2 alpha injection. A transient decrease in epinephrine and fluoride stimulation of AC was also observed, the response returning to normal 6-12 h after PGF2 alpha treatment. In vitro incubation of whole isolated CL with 0.005 micrometer or higher concentrations of PGF2 alpha markedly reduced the LH and fluoride stimulation of AC in the CL membranes. Exposure of CL to PGF2 alpha for 15 min in vitro reduced the LH and fluoride response. The results are discussed in relation to the suppressive action of PGF2 alpha on LH receptors in CL, and a mechanism is proposed to explain the discrepancy in time relation between our results and the LH receptor studies. The proposed mechanism might also explain the transient decrease in epinephrine and fluoride stimulation of AC."}
{"id": "PMID:220290", "title": "A simple direct assay of 3',5'-cyclic nucleotide phosphodiesterase activity based on the use of polyacrylamide-bononate affinity gel chromatography.", "content": "A rapid, simple, and direct assay for 3',5'-cyclic nucleotide phospho-diesterase activity is based on the effective separation of cyclic AMP, cyclic GMP or cyclic CMP from their corresponding 5'-nucleotides and nucleosides by chromatography on a polyacrylamide-boronate gel. The affinity of the boronate residue for cis-diols results in the retention of 5'nucleotides and nucleosides while 3',5'-cyclic nucleotides are not retained. The coelution of all 5'-nucleotides and nucleosides allows for the accurate assessment of phosphodiesterase activity in preparations contaminated by other purine metabolizing enzymes such as 5'-nucleotidases and nucleotide and nucleoside deaminases. Phosphodiesterase activity assayed by this means yields linear reaction kinetics with respect to time and amount of enzyme protein. Low blank values obtained allow for detection of as little as 2-3% conversion of substrate to product.", "contents": "A simple direct assay of 3',5'-cyclic nucleotide phosphodiesterase activity based on the use of polyacrylamide-bononate affinity gel chromatography. A rapid, simple, and direct assay for 3',5'-cyclic nucleotide phospho-diesterase activity is based on the effective separation of cyclic AMP, cyclic GMP or cyclic CMP from their corresponding 5'-nucleotides and nucleosides by chromatography on a polyacrylamide-boronate gel. The affinity of the boronate residue for cis-diols results in the retention of 5'nucleotides and nucleosides while 3',5'-cyclic nucleotides are not retained. The coelution of all 5'-nucleotides and nucleosides allows for the accurate assessment of phosphodiesterase activity in preparations contaminated by other purine metabolizing enzymes such as 5'-nucleotidases and nucleotide and nucleoside deaminases. Phosphodiesterase activity assayed by this means yields linear reaction kinetics with respect to time and amount of enzyme protein. Low blank values obtained allow for detection of as little as 2-3% conversion of substrate to product."}
{"id": "PMID:220291", "title": "Compatibility of various materials with oral tissues. I: The components in composite restorations.", "content": "The basic ingredients in composite restorative materials include: monomers, polymerization stabilizers, color stabilizers, polymerization initiators, polymerization accelerators, inorganic reinforcing fillers, and coupling agents. Typical members of each category are discussed.", "contents": "Compatibility of various materials with oral tissues. I: The components in composite restorations. The basic ingredients in composite restorative materials include: monomers, polymerization stabilizers, color stabilizers, polymerization initiators, polymerization accelerators, inorganic reinforcing fillers, and coupling agents. Typical members of each category are discussed."}
{"id": "PMID:220299", "title": "Effects of the aflatoxins on ATPase activities in mouse and rat liver.", "content": "The effects of the aflatoxins on ATPase activities in mouse and rat tissues were investigated in vitro. The hepatic oligomycin-sensitive (O.S.) Mg++ ATPase was inhibited significantly. The order of inhibition was G1 greater than B1 greater than G2 greater than B2. Mouse O.S. Mg++ ATPase was more sensitive than the corresponding rat enzyme. The oligomycin-insensitive (O.I.) Mg++ ATPase activities in rat and mouse liver were not altered. Although aflatoxins G1 and B1 were more potent inhibitors of hepatic O.S. Mg++ ATPase, no concentration-response was observed, whereas aflatoxins G2 and B2 inhibited enzyme activity in a concentration-dependent manner. Spectral analysis of aflatoxin G1 solutions suggested that solubility was not related to the observed effects. In addition, the effects of aflatoxin B1 and G1 on mouse brain microsomal Na+-K+ ATPase were examined. Although aflatoxin B1 was more potent that G1, both mycotoxins significantly inhibited enzyme activity in a concentration-dependent fashion.", "contents": "Effects of the aflatoxins on ATPase activities in mouse and rat liver. The effects of the aflatoxins on ATPase activities in mouse and rat tissues were investigated in vitro. The hepatic oligomycin-sensitive (O.S.) Mg++ ATPase was inhibited significantly. The order of inhibition was G1 greater than B1 greater than G2 greater than B2. Mouse O.S. Mg++ ATPase was more sensitive than the corresponding rat enzyme. The oligomycin-insensitive (O.I.) Mg++ ATPase activities in rat and mouse liver were not altered. Although aflatoxins G1 and B1 were more potent inhibitors of hepatic O.S. Mg++ ATPase, no concentration-response was observed, whereas aflatoxins G2 and B2 inhibited enzyme activity in a concentration-dependent manner. Spectral analysis of aflatoxin G1 solutions suggested that solubility was not related to the observed effects. In addition, the effects of aflatoxin B1 and G1 on mouse brain microsomal Na+-K+ ATPase were examined. Although aflatoxin B1 was more potent that G1, both mycotoxins significantly inhibited enzyme activity in a concentration-dependent fashion."}
{"id": "PMID:220324", "title": "Multiangle light scattering flow photometry of cultured human fibroblasts: comparison of normal cells with a mutant line containing cytoplasmic inclusions.", "content": "Multi-angle light scattering flow photometry was used to study the light scattering properties of normal cultured fibroblasts and a mutant fibroblast line containing cytoplasmic lysosomal inclusions. The effect of glutaraldehyde fixation on the light scattering properties of the cells was also examined and correlated with their ultrastructure. Normal fibroblasts showed uniform organelle distribution with few vacuoles or dense bodies in the cytoplasm while the mutant line showed abnormal cytoplasmic inclusions of varying morphology, density and lucency. As predicted by light scattering theory, the mutant cells containing the cytoplasmic inclusions scattered more light at large angles (greater than theta = 1.85 degrees) than did the normal cells. Glutaraldehyde fixation decreased light scattering at small angles (less than theta = 1.85 degrees), increased light scattering at larger angles (greater than theta = 1.85 degrees) in both normal and mutant cells and enhanced resolution of the light scattering signatures. The mutant line scattered 2-3 times more light at a wide angle (greater than theta = 12.74 degrees) than did the normal cells. These data suggest that abnormal lysosomal storage inclusion bodies in the cytoplasm of the cells can be detected by differential light scattering methods.", "contents": "Multiangle light scattering flow photometry of cultured human fibroblasts: comparison of normal cells with a mutant line containing cytoplasmic inclusions. Multi-angle light scattering flow photometry was used to study the light scattering properties of normal cultured fibroblasts and a mutant fibroblast line containing cytoplasmic lysosomal inclusions. The effect of glutaraldehyde fixation on the light scattering properties of the cells was also examined and correlated with their ultrastructure. Normal fibroblasts showed uniform organelle distribution with few vacuoles or dense bodies in the cytoplasm while the mutant line showed abnormal cytoplasmic inclusions of varying morphology, density and lucency. As predicted by light scattering theory, the mutant cells containing the cytoplasmic inclusions scattered more light at large angles (greater than theta = 1.85 degrees) than did the normal cells. Glutaraldehyde fixation decreased light scattering at small angles (less than theta = 1.85 degrees), increased light scattering at larger angles (greater than theta = 1.85 degrees) in both normal and mutant cells and enhanced resolution of the light scattering signatures. The mutant line scattered 2-3 times more light at a wide angle (greater than theta = 12.74 degrees) than did the normal cells. These data suggest that abnormal lysosomal storage inclusion bodies in the cytoplasm of the cells can be detected by differential light scattering methods."}
{"id": "PMID:220325", "title": "Autofluorescence of viable cultured mammalian cells.", "content": "The autofluorescence other than intrinsic protein emission of viable cultured mammalian cells has been investigated. The fluorescence was found to originate in discrete cytoplasmic vesicle-like regions and to be absent from the nucleus. Excitation and emission spectra of viable cells revealed at least two distinct fluorescent species. Comparison of cell spectra with spectra of known cellular metabolites suggested that most, if not all, of the fluorescence arises from intracellular nicotinamide adenine dinucleotide (NADH) and riboflavin and flavin coenzymes. Various changes in culture conditions did not affect the observed autofluorescence intensity. A multiparameter flow system (MACCS) was used to compare the fluorescence intensities of numerous cultured mammalian cells.", "contents": "Autofluorescence of viable cultured mammalian cells. The autofluorescence other than intrinsic protein emission of viable cultured mammalian cells has been investigated. The fluorescence was found to originate in discrete cytoplasmic vesicle-like regions and to be absent from the nucleus. Excitation and emission spectra of viable cells revealed at least two distinct fluorescent species. Comparison of cell spectra with spectra of known cellular metabolites suggested that most, if not all, of the fluorescence arises from intracellular nicotinamide adenine dinucleotide (NADH) and riboflavin and flavin coenzymes. Various changes in culture conditions did not affect the observed autofluorescence intensity. A multiparameter flow system (MACCS) was used to compare the fluorescence intensities of numerous cultured mammalian cells."}
{"id": "PMID:220326", "title": "Differences in flow cytometry and 3H-thymidine analyses of perturbed human lymphocytes.", "content": "A calf thymocyte crude aqueous extract was tested for DNA synthesis inhibitory activity using phytohemagglutinin-stimulated human peripheral blood lymphocytes. Inhibition of DNA synthesis was assayed using tritiated thymidine and flow cytometry. Although the calf thymocyte crude extract inhibited tritiated thymidine incorporation by over 50%, only very slight changes in the flow cytometric analysis were observed. When dibutyryl-cyclic adenosine monophosphate was used as an inhibitor, a correlation in terms of the inhibition of tritiated thymidine to the inhibition by flow cytometry was observed.", "contents": "Differences in flow cytometry and 3H-thymidine analyses of perturbed human lymphocytes. A calf thymocyte crude aqueous extract was tested for DNA synthesis inhibitory activity using phytohemagglutinin-stimulated human peripheral blood lymphocytes. Inhibition of DNA synthesis was assayed using tritiated thymidine and flow cytometry. Although the calf thymocyte crude extract inhibited tritiated thymidine incorporation by over 50%, only very slight changes in the flow cytometric analysis were observed. When dibutyryl-cyclic adenosine monophosphate was used as an inhibitor, a correlation in terms of the inhibition of tritiated thymidine to the inhibition by flow cytometry was observed."}
{"id": "PMID:220328", "title": "Subacute infection with temperature-sensitive vesicular stomatitis virus mutant G41 in the central nervous system of mice. I. Clinical and virologic studies.", "content": "Inoculation of three- to four-week-old BALB/c mice with temperature-sensitive (ts) vesicular stomatitis virus mutant G41 produced a subacute neurological disease, initially characterized by development of lethargy, hunched posture, and ruffled fur within five to seven days after infection. More than 90% of infected mice developed these clinical signs. In approximately 60% of infected mice, the initial neurological signs proceeded to striking hind-limb paralysis and weight loss. These signs usually appeared by seven to nine days after infection and lasted for 21-28 days. Only 16% of the mice died as a result of infection; death usually occurred eight to 12 days after infection. Most of the infected mice recovered from the acute phase of disease and appeared normal by four weeks after infection. However, hind-limb paralysis persisted in 4% of the mice for as long as the mice were observed, i.e., 42 days. The mutant ts-G41 was recovered from the brains and spinal cords of infected mice for the first seven days after infection. Peak titers of virus were modest, 10(4)-10(5) pfu/ml in brain tissue and 10(3)-10(4) pfu/ml in spinal cord tissue. Virus isolated after in vivo infection was temperature-sensitive and thus not revertant wild-type virus. Although virus was recoverable by homogenization for only the first seven days of infection, use of cocultivation techniques permitted the detection of ts-G41 in brains and spinal cords of infected animals for as long as 21 days after infection. Virus recovered by cocultivation was also temperature-sensitive.", "contents": "Subacute infection with temperature-sensitive vesicular stomatitis virus mutant G41 in the central nervous system of mice. I. Clinical and virologic studies. Inoculation of three- to four-week-old BALB/c mice with temperature-sensitive (ts) vesicular stomatitis virus mutant G41 produced a subacute neurological disease, initially characterized by development of lethargy, hunched posture, and ruffled fur within five to seven days after infection. More than 90% of infected mice developed these clinical signs. In approximately 60% of infected mice, the initial neurological signs proceeded to striking hind-limb paralysis and weight loss. These signs usually appeared by seven to nine days after infection and lasted for 21-28 days. Only 16% of the mice died as a result of infection; death usually occurred eight to 12 days after infection. Most of the infected mice recovered from the acute phase of disease and appeared normal by four weeks after infection. However, hind-limb paralysis persisted in 4% of the mice for as long as the mice were observed, i.e., 42 days. The mutant ts-G41 was recovered from the brains and spinal cords of infected mice for the first seven days after infection. Peak titers of virus were modest, 10(4)-10(5) pfu/ml in brain tissue and 10(3)-10(4) pfu/ml in spinal cord tissue. Virus isolated after in vivo infection was temperature-sensitive and thus not revertant wild-type virus. Although virus was recoverable by homogenization for only the first seven days of infection, use of cocultivation techniques permitted the detection of ts-G41 in brains and spinal cords of infected animals for as long as 21 days after infection. Virus recovered by cocultivation was also temperature-sensitive."}
{"id": "PMID:220329", "title": "Subacute infection with temperature-sensitive vesicular stomatitis virus mutant G41 in the central nervous system of mice. II. Immunofluorescent, morphologic, and immunologic studies.", "content": "Inoculation of three- to four-week-old BALB/c mice with temperature-sensitive (ts) vesicular stomatitis virus (VSV) mutant G41 produced a subacute neurological disease mainly localized in the spinal cord. Meningitis and diffuse microglial infiltration of the anterior horns of the spinal cord were seen starting six days after infection when neuronal degenerative changes could be seen. Infection of neurons was demonstrated by immunofluorescence microscopy five days after infection. Two to three weeks after infection, loosening of the neuropil was evident due to neuronal dropout, and the mononuclear infiltration had become perivascularly distributed and had changed in character because of a striking increase in plasma cells. These cells together with Russell bodies became the main inflammatory cellular component about four to five weeks after viral inoculation. Starting eight days after infection, several foci of primary demyelination could be found in the anterior columns of the spinal cord. Immunological responses appeared within four days after infection when both neutralizing antibody and stimulation of specific spleen lymphocytes could be demonstrated. Serum antibody responses peaked at 21-28 days but remained elevated for up to 153 days. Stimulation of spleen lymphocyte cells peaked at 10-21 days and also remained elevated for as long as 116 days. The presence of both inflammatory changes and immunological responses to VSV mutant ts-G41 for prolonged periods is characteristic of persistent viral infections. Infection of BALB/c mice with ts-G41 thus represents the first in vivo example of persistent viral infection utilizing ts mutants of VSV.", "contents": "Subacute infection with temperature-sensitive vesicular stomatitis virus mutant G41 in the central nervous system of mice. II. Immunofluorescent, morphologic, and immunologic studies. Inoculation of three- to four-week-old BALB/c mice with temperature-sensitive (ts) vesicular stomatitis virus (VSV) mutant G41 produced a subacute neurological disease mainly localized in the spinal cord. Meningitis and diffuse microglial infiltration of the anterior horns of the spinal cord were seen starting six days after infection when neuronal degenerative changes could be seen. Infection of neurons was demonstrated by immunofluorescence microscopy five days after infection. Two to three weeks after infection, loosening of the neuropil was evident due to neuronal dropout, and the mononuclear infiltration had become perivascularly distributed and had changed in character because of a striking increase in plasma cells. These cells together with Russell bodies became the main inflammatory cellular component about four to five weeks after viral inoculation. Starting eight days after infection, several foci of primary demyelination could be found in the anterior columns of the spinal cord. Immunological responses appeared within four days after infection when both neutralizing antibody and stimulation of specific spleen lymphocytes could be demonstrated. Serum antibody responses peaked at 21-28 days but remained elevated for up to 153 days. Stimulation of spleen lymphocyte cells peaked at 10-21 days and also remained elevated for as long as 116 days. The presence of both inflammatory changes and immunological responses to VSV mutant ts-G41 for prolonged periods is characteristic of persistent viral infections. Infection of BALB/c mice with ts-G41 thus represents the first in vivo example of persistent viral infection utilizing ts mutants of VSV."}
{"id": "PMID:220330", "title": "Serologic studies of transmission of hepatitis A in humans.", "content": "In 1968, studies of infectious hepatitis in volunteers were reported. Immunologic procedures for serologic study of the hepatitis A virus were not available at that time, and only the clinical and biochemical parameters of the disease were reported. Serial serum specimens from the participants in the study were retained; these specimens had been taken before inoculation and up to more than 100 days after inoculation. When a radioimmune assay for antibody to hepatitis A virus was developed, the series of sera was analyzed retrospectively. Forty-four male volunteers were involved in a series of three studies. Twenty (46%) of the volunteers were found to be initially immune to hepatitis A virus. Eighteen susceptible volunteers (with no preexisting antibody) were challenged with infectious virus. Eight of these volunteers developed clinical hepatitis and seroconverted; one seroconverted without evidence of clinical disease; and nine neither seroconverted nor had evidence of clinical disease. The radioimmune assay provided a method for diagnosis of immune status and of the acute disease caused by hepatitis A virus.", "contents": "Serologic studies of transmission of hepatitis A in humans. In 1968, studies of infectious hepatitis in volunteers were reported. Immunologic procedures for serologic study of the hepatitis A virus were not available at that time, and only the clinical and biochemical parameters of the disease were reported. Serial serum specimens from the participants in the study were retained; these specimens had been taken before inoculation and up to more than 100 days after inoculation. When a radioimmune assay for antibody to hepatitis A virus was developed, the series of sera was analyzed retrospectively. Forty-four male volunteers were involved in a series of three studies. Twenty (46%) of the volunteers were found to be initially immune to hepatitis A virus. Eighteen susceptible volunteers (with no preexisting antibody) were challenged with infectious virus. Eight of these volunteers developed clinical hepatitis and seroconverted; one seroconverted without evidence of clinical disease; and nine neither seroconverted nor had evidence of clinical disease. The radioimmune assay provided a method for diagnosis of immune status and of the acute disease caused by hepatitis A virus."}
{"id": "PMID:220331", "title": "Isolation of a cytotoxin-enterotoxin from Entamoeba histolytica.", "content": "A heat-labile material with cytotoxic and enterotoxic activities was isolated from axenically cultivated Entamoeba histolytica. The cytotoxin-enterotoxin was partially purified from the particulate-free supernatant of sonicated trophozoites by ammonium sulfate precipitation and gel filtration. Cytotoxic activity, assayed on monolayers of HeLa or BHK-21 cells, was restricted to proteins that eluted in the molecular weight range of 25,000--35,000 daltons. Cytotoxicity was demonstrated at protein concentrations as low as 2--4 microgram/ml, was heat-labile (75 C, 30 min), and was inhibited by specific immune IgG and by an undetermined factor in nonimmune serum. Enterotoxic activity of the partially purified toxin was demonstrated by induction of fluid secretion in ligated rabbit ileal loops. The cytotoxin-enterotoxin of E. histolytica may play an important role in the production of diarrhea and mucosal injury in amoebic colitis.", "contents": "Isolation of a cytotoxin-enterotoxin from Entamoeba histolytica. A heat-labile material with cytotoxic and enterotoxic activities was isolated from axenically cultivated Entamoeba histolytica. The cytotoxin-enterotoxin was partially purified from the particulate-free supernatant of sonicated trophozoites by ammonium sulfate precipitation and gel filtration. Cytotoxic activity, assayed on monolayers of HeLa or BHK-21 cells, was restricted to proteins that eluted in the molecular weight range of 25,000--35,000 daltons. Cytotoxicity was demonstrated at protein concentrations as low as 2--4 microgram/ml, was heat-labile (75 C, 30 min), and was inhibited by specific immune IgG and by an undetermined factor in nonimmune serum. Enterotoxic activity of the partially purified toxin was demonstrated by induction of fluid secretion in ligated rabbit ileal loops. The cytotoxin-enterotoxin of E. histolytica may play an important role in the production of diarrhea and mucosal injury in amoebic colitis."}
{"id": "PMID:220333", "title": "Chronically persistent infection with human cytomegalovirus in human lymphoblasts.", "content": "Cells from a line of human lymphocytes originating from a leukemic patient were persistently infected with human cytomegalovirus. Assays of infectious centers and fluorescent antigen staining indicated that 1%--10% of the cells were infected. It appears that persistent infection is due to an equilibrium between the release of virus by infected host cells and the growth of uninfected cells rather than to defective virus or temperature-sensitive mutants.", "contents": "Chronically persistent infection with human cytomegalovirus in human lymphoblasts. Cells from a line of human lymphocytes originating from a leukemic patient were persistently infected with human cytomegalovirus. Assays of infectious centers and fluorescent antigen staining indicated that 1%--10% of the cells were infected. It appears that persistent infection is due to an equilibrium between the release of virus by infected host cells and the growth of uninfected cells rather than to defective virus or temperature-sensitive mutants."}
{"id": "PMID:220334", "title": "Travelers' diarrhea among U.S. Army troops in South Korea.", "content": "A prospective study of diarrhea was conducted among 98 U.S. Army soldiers during their first six weeks in South Korea. Diarrhea developed in 54 (55%) of 98 soldiers and had a mean duration of five days. Infections with Salmonella, Shigella, Vibrio, enterotoxigenic Escherichia coli, enteroviruses, and intestinal parasites were uncommon. Four (8%) of 50 soldiers with documented diarrhea, two (6%) or 32 with a history of diarrhea, and one (3%) of 29 who denied gastrointestinal symptoms had serologic evidence of a recent rotavirus infection. The etiology of diarrhea among U.S. soldiers who had recently arrived in South Korea differed from the etiology among travelers in warmer climates, where enterotoxigenic strains of E. coli were responsible for the majority of cases. Further efforts are needed to define other enteric pathogens in the etiology of diarrhea among new arrivals in different parts of the world.", "contents": "Travelers' diarrhea among U.S. Army troops in South Korea. A prospective study of diarrhea was conducted among 98 U.S. Army soldiers during their first six weeks in South Korea. Diarrhea developed in 54 (55%) of 98 soldiers and had a mean duration of five days. Infections with Salmonella, Shigella, Vibrio, enterotoxigenic Escherichia coli, enteroviruses, and intestinal parasites were uncommon. Four (8%) of 50 soldiers with documented diarrhea, two (6%) or 32 with a history of diarrhea, and one (3%) of 29 who denied gastrointestinal symptoms had serologic evidence of a recent rotavirus infection. The etiology of diarrhea among U.S. soldiers who had recently arrived in South Korea differed from the etiology among travelers in warmer climates, where enterotoxigenic strains of E. coli were responsible for the majority of cases. Further efforts are needed to define other enteric pathogens in the etiology of diarrhea among new arrivals in different parts of the world."}
{"id": "PMID:220335", "title": "Seroimmunity to polioviruses in U.S. Army recruits.", "content": "Titers of neutralizing antibody to poliovirus types 1, 2, and 3 were determined for serum specimens obtained from 268 U.S. Army recruits. Among those tested, 20.9% lacked neutralizing antibody to one or more types of poliovirus, and 1.1% lacked antibody to all three types. An analysis of demographic data showed that age of less than 18 years, schooling for less than 10 years, and residence in the northeastern United States were associated with higher percentages of recruits lacking neutralizing antibodies to polioviruses in serum.", "contents": "Seroimmunity to polioviruses in U.S. Army recruits. Titers of neutralizing antibody to poliovirus types 1, 2, and 3 were determined for serum specimens obtained from 268 U.S. Army recruits. Among those tested, 20.9% lacked neutralizing antibody to one or more types of poliovirus, and 1.1% lacked antibody to all three types. An analysis of demographic data showed that age of less than 18 years, schooling for less than 10 years, and residence in the northeastern United States were associated with higher percentages of recruits lacking neutralizing antibodies to polioviruses in serum."}
{"id": "PMID:220336", "title": "Complement-enhanced neutralizing antibody response to varicella-zoster virus.", "content": "Humoral immunity following infection with varicella-zoster virus (VZV) was evaluated by a complement-enhanced neutralization test. The specificity of the test was examined and its sensitivity compared with that of the assay which measures antibody to VZV-induced membrane antigen (FAMA). Generally, the titer of neurtalizing antibody was two- to fourfold higher than the FAMA titer. The absence of neutralizing activity at a serum dilution of 1:4 indicated susceptibility of the donor to VZV infection and correlated with an absence of FAMA (titer, less than 1:2). A survey of susceptible leukemic children exposed to chicken pox revealed that several recipients of zoster immune globulin had a subclinical infection, as manifested by seroconversion and persistence of neutralizing antibody to VZV. Results of these studies indicate that the complement-enhanced neutralization test is a sensitive and specific assay for determination of humoral immune status with regard to VZV in healthy and immunosuppressed individuals.", "contents": "Complement-enhanced neutralizing antibody response to varicella-zoster virus. Humoral immunity following infection with varicella-zoster virus (VZV) was evaluated by a complement-enhanced neutralization test. The specificity of the test was examined and its sensitivity compared with that of the assay which measures antibody to VZV-induced membrane antigen (FAMA). Generally, the titer of neurtalizing antibody was two- to fourfold higher than the FAMA titer. The absence of neutralizing activity at a serum dilution of 1:4 indicated susceptibility of the donor to VZV infection and correlated with an absence of FAMA (titer, less than 1:2). A survey of susceptible leukemic children exposed to chicken pox revealed that several recipients of zoster immune globulin had a subclinical infection, as manifested by seroconversion and persistence of neutralizing antibody to VZV. Results of these studies indicate that the complement-enhanced neutralization test is a sensitive and specific assay for determination of humoral immune status with regard to VZV in healthy and immunosuppressed individuals."}
{"id": "PMID:220337", "title": "Relapse of pneumonia caused by cytomegalovirus in two recipients of renal transplants.", "content": "Two cases of relapse of pneumonia caused by cytomegalovirus (CMV) in recipients of renal transplants were studied. Between episodes of pneumonia, both patients recovered completely as judged by X-ray clearing and by resolution of fever and respiratory symptoms. CMV was isolated during each episode of pneumonia from lung tissue, pleural fluid, or buffy coat cultures. Serologic studies revealed a rise in titer of antibody, confirming recent infection with CMV during the first epidose of pneumonia in each patient. Intranuclear inclusions consistent with CMV infection were detected in each of the three episodes where lung tissue was obtained. Special stains and cultures for Pneumocystis carinii, fungi, Nocardia, and mycobacteria yielded negative results. The renal allograft continued to function in both patients after they recovered from the first bout of pneumonia, and the relapse was temporally related to reinstitution of aggressive immunosuppressive therapy. The relapse of pneumonia emphasizes the need for caution when immunosuppressive therapy is reinstituted after recovery from serious CMV infection.", "contents": "Relapse of pneumonia caused by cytomegalovirus in two recipients of renal transplants. Two cases of relapse of pneumonia caused by cytomegalovirus (CMV) in recipients of renal transplants were studied. Between episodes of pneumonia, both patients recovered completely as judged by X-ray clearing and by resolution of fever and respiratory symptoms. CMV was isolated during each episode of pneumonia from lung tissue, pleural fluid, or buffy coat cultures. Serologic studies revealed a rise in titer of antibody, confirming recent infection with CMV during the first epidose of pneumonia in each patient. Intranuclear inclusions consistent with CMV infection were detected in each of the three episodes where lung tissue was obtained. Special stains and cultures for Pneumocystis carinii, fungi, Nocardia, and mycobacteria yielded negative results. The renal allograft continued to function in both patients after they recovered from the first bout of pneumonia, and the relapse was temporally related to reinstitution of aggressive immunosuppressive therapy. The relapse of pneumonia emphasizes the need for caution when immunosuppressive therapy is reinstituted after recovery from serious CMV infection."}
{"id": "PMID:220338", "title": "Presence of two distinct types of rotavirus in infants and young children hospitalized with acute gastroenteritis in Mexico City, 1977.", "content": "Between December 1976 and January 1978, infection with rotavirus was detected by electron microscopy in 61 (25%) of 242 infants and young children hospitalized with acute gastroenteritis at two hospitals in Mexico City. This type of infection was more frequent in autumn than in winter. The presence of virus could also be detected by the electrophoretic pattern of its segmented, double-standed ribonucleic acid (RNA) in the stool samples taken from 52 (85%) of the 61 patients who were shown by electron microscopic examination to excrete rotavirus. Two distinct patterns, previously called 2s and 21, were observed, which were distinguishable by the relative migration of the second, 10th, and 11th viral RNA segments in gel electrophoresis; the 21 pattern was observed much more frequently than with the 2s pattern.", "contents": "Presence of two distinct types of rotavirus in infants and young children hospitalized with acute gastroenteritis in Mexico City, 1977. Between December 1976 and January 1978, infection with rotavirus was detected by electron microscopy in 61 (25%) of 242 infants and young children hospitalized with acute gastroenteritis at two hospitals in Mexico City. This type of infection was more frequent in autumn than in winter. The presence of virus could also be detected by the electrophoretic pattern of its segmented, double-standed ribonucleic acid (RNA) in the stool samples taken from 52 (85%) of the 61 patients who were shown by electron microscopic examination to excrete rotavirus. Two distinct patterns, previously called 2s and 21, were observed, which were distinguishable by the relative migration of the second, 10th, and 11th viral RNA segments in gel electrophoresis; the 21 pattern was observed much more frequently than with the 2s pattern."}
{"id": "PMID:220339", "title": "Evaluation of indirect hemagglutination and its inhibition in the differentiation between antibodies to herpes simplex virus types 1 and 2 for seroepidemiologic studies: use of a II/I index threshold of 85 and an assay of type-specific antibodies.", "content": "Two parameters, a II/I index threshold value of 85 and an assay of type-specific antibodies to herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), were assessed, for seroepidemiologic purposes, for their efficacy in the establishment of past infections with HSV-1 and HSV-2 as indicated by the results of tests for indirect hemagglutination and its inhibition. Neither criterion alone established past infection with either HSV-1 or HSV-2. However, by combination of the two parameters, antibodies to HSV-1 and HSV-2 could be differentiated for seroepidemiologic studies.", "contents": "Evaluation of indirect hemagglutination and its inhibition in the differentiation between antibodies to herpes simplex virus types 1 and 2 for seroepidemiologic studies: use of a II/I index threshold of 85 and an assay of type-specific antibodies. Two parameters, a II/I index threshold value of 85 and an assay of type-specific antibodies to herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), were assessed, for seroepidemiologic purposes, for their efficacy in the establishment of past infections with HSV-1 and HSV-2 as indicated by the results of tests for indirect hemagglutination and its inhibition. Neither criterion alone established past infection with either HSV-1 or HSV-2. However, by combination of the two parameters, antibodies to HSV-1 and HSV-2 could be differentiated for seroepidemiologic studies."}
{"id": "PMID:220340", "title": "Primary infection with Epstein-Barr virus in infants in the United States: clinical and serologic observations.", "content": "Previous studies in Ghana had shown that primary infections with Epstein-Barr virus in infants under the age of two years remain silent and evoke antibody responses different from those seen in infectious mononucleosis. In order to determine whether or not these observations were limited to Africa, 80 American infants presenting with minor infectious complaints were studied serologically; 14 (17.5%) showed evidence of recent or current primary infections with Epstein-Barr virus. The clinical features of these 14 infants were similar to those of the other 66 and did not suggest a diagnosis of infectious mononucleosis, nor were there histories of a recent infectious mononucleosis-like illness. Ten (72%) had antibodies to the early antigen complex induced by Epstein-Barr virus; however, these antibodies were directed, as in the Ghanaian infants, against the restricted rather than the diffuse components, in contrast to the pattern generally observed in infectious mononucleosis. Possible reasons for the differences between the responses of infants and those of older individuals to primary infection with Epstein-Barr virus and to the early antigen complex are discussed.", "contents": "Primary infection with Epstein-Barr virus in infants in the United States: clinical and serologic observations. Previous studies in Ghana had shown that primary infections with Epstein-Barr virus in infants under the age of two years remain silent and evoke antibody responses different from those seen in infectious mononucleosis. In order to determine whether or not these observations were limited to Africa, 80 American infants presenting with minor infectious complaints were studied serologically; 14 (17.5%) showed evidence of recent or current primary infections with Epstein-Barr virus. The clinical features of these 14 infants were similar to those of the other 66 and did not suggest a diagnosis of infectious mononucleosis, nor were there histories of a recent infectious mononucleosis-like illness. Ten (72%) had antibodies to the early antigen complex induced by Epstein-Barr virus; however, these antibodies were directed, as in the Ghanaian infants, against the restricted rather than the diffuse components, in contrast to the pattern generally observed in infectious mononucleosis. Possible reasons for the differences between the responses of infants and those of older individuals to primary infection with Epstein-Barr virus and to the early antigen complex are discussed."}
{"id": "PMID:220341", "title": "Role of Norwalk virus in outbreaks of nonbacterial gastroenteritis.", "content": "Twenty-five separate outbreaks of nonbacterial gastrointestinal illnesses were studied serologically for evidence of infection with the Norwalk virus and the rotaviruses that affect humans. Eight of 25 outbreaks appeared to be related to the Norwalk virus. In one of the 25 outbreaks, there was evidence of rotavirus infection. These observations suggest that the Norwalk virus or serologically related agents play an important role in epidemic nonbacterial gastroenteritis in adults and older children.", "contents": "Role of Norwalk virus in outbreaks of nonbacterial gastroenteritis. Twenty-five separate outbreaks of nonbacterial gastrointestinal illnesses were studied serologically for evidence of infection with the Norwalk virus and the rotaviruses that affect humans. Eight of 25 outbreaks appeared to be related to the Norwalk virus. In one of the 25 outbreaks, there was evidence of rotavirus infection. These observations suggest that the Norwalk virus or serologically related agents play an important role in epidemic nonbacterial gastroenteritis in adults and older children."}
{"id": "PMID:220342", "title": "Ornidazole and anaerobic bacteria: in vitro sensitivity and effects on wound infections after appendectomy.", "content": "The sensitivities of 68 clinical isolates of Bacteroides fragilis, 18 of Clostridium perfringens, and 11 of other Clostridium species were tested against ornidazole alone and in combination with ampicillin and gentamicin. A concentration of 3.1 microgram of ornidazole/ml inhibited 98% of the strains of B. fragilis, with greater sensitivity when ampicillin and gentamicin were also present. A concentration of 6.2 microgram of ornidazole/ml inhibited 16 of 18 strains of C. perfringens and all 11 strains of other Clostridium species. Concentrations in serum and tissue were determined after intravenous infusion of 500 mg of ornidazole 15 min prior to appendectomy. During the operation the concentration in serum was 7.90 +/- 0.57 microgram/ml, and in appendix tissue, 5.26 +/- 0.60 microgram/g. In the series of 200 patients undergoing appendectomy, six patients treated with ornidazole and 12 patients treated with placebo developed a wound infection. In patients with perforated appendix, the rate of wound infection was 7.1% in those given ornidazole and 63.6% in those given placebo (P = 0.004). Not a single B. fragilis was isolated from appendix swabs or wound exudates after prophylaxis with ornidazole.", "contents": "Ornidazole and anaerobic bacteria: in vitro sensitivity and effects on wound infections after appendectomy. The sensitivities of 68 clinical isolates of Bacteroides fragilis, 18 of Clostridium perfringens, and 11 of other Clostridium species were tested against ornidazole alone and in combination with ampicillin and gentamicin. A concentration of 3.1 microgram of ornidazole/ml inhibited 98% of the strains of B. fragilis, with greater sensitivity when ampicillin and gentamicin were also present. A concentration of 6.2 microgram of ornidazole/ml inhibited 16 of 18 strains of C. perfringens and all 11 strains of other Clostridium species. Concentrations in serum and tissue were determined after intravenous infusion of 500 mg of ornidazole 15 min prior to appendectomy. During the operation the concentration in serum was 7.90 +/- 0.57 microgram/ml, and in appendix tissue, 5.26 +/- 0.60 microgram/g. In the series of 200 patients undergoing appendectomy, six patients treated with ornidazole and 12 patients treated with placebo developed a wound infection. In patients with perforated appendix, the rate of wound infection was 7.1% in those given ornidazole and 63.6% in those given placebo (P = 0.004). Not a single B. fragilis was isolated from appendix swabs or wound exudates after prophylaxis with ornidazole."}
{"id": "PMID:220347", "title": "Clinical significance of serum angiotensin-converting enzyme levels in sarcoidosis.", "content": "Determinations of SACE activity were performed in 80 patients with sarcoidosis, 55 normal controls, and 29 patients with asthma, by the spectrophotometric method of Cushman and Cheung. SACE levels were significantly higher in both untreated and steroid-treated patients with sarcoidosis than in normal controls: 46.2 +/- 20.6 (S.D.), nm/min/ml, 38.1 +/- 23.1, and 26.8 +/- 1.8, respectively. There were no significant differences between steroid-treated and untreated patient groups. However, an inverse correlation was observed between SACE levels and steroid dose, suggesting the possibility of a dose dependency for steroid-induced depression of SACE. Elevated SACE levels (2 S.D. above mean controls) were present in 67% of untreated sarcoidosis patients. The prevalence of elevated SACE levels was not significantly higher when the patient population was examined with respect to duration of disease, radiological stage, and the presence of abnormality in pulmonary function tests. When patients were divided according to the frequency of clinical criteria of disease activity, the presence of two or more criteria was associated with elevated SACE levels in 88% of patients. But SACE levels were elevated in 32% of patients judged to have dormant disease by clinical criteria. SACE levels had an 81% accuracy in prediction of disease activity and a 79% accruacy for prediction of inactivity. It was concluded that SACE elevations have definite diagnostic value in sarcoidosis and are helpful in establishing the presence of disease activity but are not sufficient to fully separate active from inactive disease groups.", "contents": "Clinical significance of serum angiotensin-converting enzyme levels in sarcoidosis. Determinations of SACE activity were performed in 80 patients with sarcoidosis, 55 normal controls, and 29 patients with asthma, by the spectrophotometric method of Cushman and Cheung. SACE levels were significantly higher in both untreated and steroid-treated patients with sarcoidosis than in normal controls: 46.2 +/- 20.6 (S.D.), nm/min/ml, 38.1 +/- 23.1, and 26.8 +/- 1.8, respectively. There were no significant differences between steroid-treated and untreated patient groups. However, an inverse correlation was observed between SACE levels and steroid dose, suggesting the possibility of a dose dependency for steroid-induced depression of SACE. Elevated SACE levels (2 S.D. above mean controls) were present in 67% of untreated sarcoidosis patients. The prevalence of elevated SACE levels was not significantly higher when the patient population was examined with respect to duration of disease, radiological stage, and the presence of abnormality in pulmonary function tests. When patients were divided according to the frequency of clinical criteria of disease activity, the presence of two or more criteria was associated with elevated SACE levels in 88% of patients. But SACE levels were elevated in 32% of patients judged to have dormant disease by clinical criteria. SACE levels had an 81% accuracy in prediction of disease activity and a 79% accruacy for prediction of inactivity. It was concluded that SACE elevations have definite diagnostic value in sarcoidosis and are helpful in establishing the presence of disease activity but are not sufficient to fully separate active from inactive disease groups."}
{"id": "PMID:220348", "title": "The ultrastructure of cholesterol granuloma of the middle ear: an electron microscope study.", "content": "The ultrastructure of giant cells in cholesterol granuloma is described, with particular reference to their role in the absorption of cholesterol needles. Cholesterol is a highly resistant substance in its crystalline form and it is confirmed that the giant cells are endowed with endoplasmic structures and organelles and are partly crowded with lysosomes, as evidence of the active role of the giant cells in the absorption and removal of cholesterol formed in the granuloma from blood, mucus or necrotic material.", "contents": "The ultrastructure of cholesterol granuloma of the middle ear: an electron microscope study. The ultrastructure of giant cells in cholesterol granuloma is described, with particular reference to their role in the absorption of cholesterol needles. Cholesterol is a highly resistant substance in its crystalline form and it is confirmed that the giant cells are endowed with endoplasmic structures and organelles and are partly crowded with lysosomes, as evidence of the active role of the giant cells in the absorption and removal of cholesterol formed in the granuloma from blood, mucus or necrotic material."}
{"id": "PMID:220350", "title": "Prostaglandin synthesis in rat adrenocortical cells.", "content": "The biosynthesis of prostaglandins by isolated rat adrenocortical cells has been studied by determinations of products formed during incubations with labeled arachidonic acid and by radioimmunoassays. Analysis by thin-layer chromatographic separation of silicic acid column fractions indicated that PGE2, PGA2, (B2) and PGF2 alpha were the predominant prostaglandins formed by rat adrenocortical cells. Approximately 75% of the incorporated isotope was associated with the prostaglandins of the PGE pathway [PGE2 + PGA2 (B2)]. This was a consistent finding whether cells were incubated directly with arachidonic acid or with cells prelabeled with the substrate prior to study. ACTH did not affect the uptake or oxidation of [1-14C]-arachidonate, but did significantly increase incorporation of labeled substrate into [14C]prostaglandins. Of the ACTH-induced increase, 92% was accounted for by an increase in prostaglandins of the E pathway. Studies with prelabeled cells indicated that 77% of the prostaglandins synthesized in both control and ACTH-stimulated adrenocortical cells was released into the incubation medium during the 2-hr study. These had the same composition [88% PGE2 + PGA2 (B2)] as did the intracellular prostaglandins. Analysis by radioimmunoassays gave comparable data on the distribution of E- and F-type prostaglandins in control cells and cells incubated with ACTH or dibutyryl cyclic AMP. Thus, with these techniques, 88-92% of the increased prostaglandin synthesis due to ACTH or cyclic AMP was produced by the PGE2 rather than the PGF2 alpha pathway.", "contents": "Prostaglandin synthesis in rat adrenocortical cells. The biosynthesis of prostaglandins by isolated rat adrenocortical cells has been studied by determinations of products formed during incubations with labeled arachidonic acid and by radioimmunoassays. Analysis by thin-layer chromatographic separation of silicic acid column fractions indicated that PGE2, PGA2, (B2) and PGF2 alpha were the predominant prostaglandins formed by rat adrenocortical cells. Approximately 75% of the incorporated isotope was associated with the prostaglandins of the PGE pathway [PGE2 + PGA2 (B2)]. This was a consistent finding whether cells were incubated directly with arachidonic acid or with cells prelabeled with the substrate prior to study. ACTH did not affect the uptake or oxidation of [1-14C]-arachidonate, but did significantly increase incorporation of labeled substrate into [14C]prostaglandins. Of the ACTH-induced increase, 92% was accounted for by an increase in prostaglandins of the E pathway. Studies with prelabeled cells indicated that 77% of the prostaglandins synthesized in both control and ACTH-stimulated adrenocortical cells was released into the incubation medium during the 2-hr study. These had the same composition [88% PGE2 + PGA2 (B2)] as did the intracellular prostaglandins. Analysis by radioimmunoassays gave comparable data on the distribution of E- and F-type prostaglandins in control cells and cells incubated with ACTH or dibutyryl cyclic AMP. Thus, with these techniques, 88-92% of the increased prostaglandin synthesis due to ACTH or cyclic AMP was produced by the PGE2 rather than the PGF2 alpha pathway."}
{"id": "PMID:220351", "title": "The effect of glucagon, norepinephrine, and dibutyryl cyclic AMP on cholesterol efflux and on the activity of 3-hydroxy-3-methylglutaryl CoA reductase in rat hepatocytes.", "content": "Incubation of rat hepatocytes for 3 hours in a sterol-free medium containing 1.5% albumin resulted in efflux of cellular sterol into the medium and an increased activity of 3-hydroxy-3-methylglutaryl CoA reductase. The secretion of cholesterol was inhibited when cells were incubated with glucagon, norepinephrine, or dibutyryl cyclic AMP. Glucagon and dibutyryl cyclic AMP also inhibited the induction of HMG-CoA reductase. Norepinephrine treatment resulted in a decrease in the synthesis and secretion of proteins but caused an increase in reductase activity. Insulin treatment had no effect either on reductase activity or on sterol efflux from rat hepatocytes.", "contents": "The effect of glucagon, norepinephrine, and dibutyryl cyclic AMP on cholesterol efflux and on the activity of 3-hydroxy-3-methylglutaryl CoA reductase in rat hepatocytes. Incubation of rat hepatocytes for 3 hours in a sterol-free medium containing 1.5% albumin resulted in efflux of cellular sterol into the medium and an increased activity of 3-hydroxy-3-methylglutaryl CoA reductase. The secretion of cholesterol was inhibited when cells were incubated with glucagon, norepinephrine, or dibutyryl cyclic AMP. Glucagon and dibutyryl cyclic AMP also inhibited the induction of HMG-CoA reductase. Norepinephrine treatment resulted in a decrease in the synthesis and secretion of proteins but caused an increase in reductase activity. Insulin treatment had no effect either on reductase activity or on sterol efflux from rat hepatocytes."}
{"id": "PMID:220352", "title": "Low density lipoprotein metabolism and lipoprotein cholesterol content in southwestern American Indians.", "content": "The prevalence of ischemic heart disease is significantly lower in southwestern American Indians than in Caucasians. To investigate this difference, the metabolism of low density lipoprotein apoprotein (apo-LDL) and plasma lipoprotein cholesterol composition were studied in 10 southwestern American Indians and 5 Caucasian controls. The plasma concentration of LDL cholesterol in American Indians was 88 +/- 5 mg/dl (mean +/- SEM) and 111 +/- 7 mg/dl in Caucasians. The corresponding values of apo-LDL concentrations were 53 +/- 3 mg/dl and 77 +/- 4 mg/dl, respectively. Conversely, high density lipoprotein cholesterol (HDL) concentrations were significantly higher in American Indians (56 +/- 4 mg/dl) than in Caucasians (37 +/- 3 mg/dl). There were no statistically significant differences in the biological half-life of apo-LDL, calculated from the second exponential of the plasma die-away curve (3.06 +/- 0.15 days vs. 3.45 +/- 0.11 days), the fractional catabolic rate of apo-LDL (0.432 +/- 0.01 vs. 0.411 +/- 0.01), or the fraction of total exchangeable apo-LDL in the intravascular space (70 +/- 1 vs. 67 +/- 3%). As derived from the absolute catabolic rate under steady-state conditions, the synthetic rate of apo-LDL in American Indians was, however, significantly lower than in Caucasians (334.6 +/- 7.8 mg/m(2) per day vs. 507.2 +/- 6.7 mg/m(2) per day; P < 0.001). These data indicate that the lower levels of plasma LDL cholesterol and apo-LDL in American Indians are due to a reduced rate of apo-LDL synthesis rather than to differences in fractional catabolic rates. These differences, in combination with higher HDL cholesterol levels, may contribute to the lower prevalence of ischemic heart disease in American Indians.", "contents": "Low density lipoprotein metabolism and lipoprotein cholesterol content in southwestern American Indians. The prevalence of ischemic heart disease is significantly lower in southwestern American Indians than in Caucasians. To investigate this difference, the metabolism of low density lipoprotein apoprotein (apo-LDL) and plasma lipoprotein cholesterol composition were studied in 10 southwestern American Indians and 5 Caucasian controls. The plasma concentration of LDL cholesterol in American Indians was 88 +/- 5 mg/dl (mean +/- SEM) and 111 +/- 7 mg/dl in Caucasians. The corresponding values of apo-LDL concentrations were 53 +/- 3 mg/dl and 77 +/- 4 mg/dl, respectively. Conversely, high density lipoprotein cholesterol (HDL) concentrations were significantly higher in American Indians (56 +/- 4 mg/dl) than in Caucasians (37 +/- 3 mg/dl). There were no statistically significant differences in the biological half-life of apo-LDL, calculated from the second exponential of the plasma die-away curve (3.06 +/- 0.15 days vs. 3.45 +/- 0.11 days), the fractional catabolic rate of apo-LDL (0.432 +/- 0.01 vs. 0.411 +/- 0.01), or the fraction of total exchangeable apo-LDL in the intravascular space (70 +/- 1 vs. 67 +/- 3%). As derived from the absolute catabolic rate under steady-state conditions, the synthetic rate of apo-LDL in American Indians was, however, significantly lower than in Caucasians (334.6 +/- 7.8 mg/m(2) per day vs. 507.2 +/- 6.7 mg/m(2) per day; P < 0.001). These data indicate that the lower levels of plasma LDL cholesterol and apo-LDL in American Indians are due to a reduced rate of apo-LDL synthesis rather than to differences in fractional catabolic rates. These differences, in combination with higher HDL cholesterol levels, may contribute to the lower prevalence of ischemic heart disease in American Indians."}
{"id": "PMID:220353", "title": "Study of the atherogenic dyslipoproteinemia induced by dietary cholesterol in rhesus monekys (Macaca mulatta).", "content": "Hypercholesterolemia was induced in adult male rhesus monkeys with a high-fat diet containing an elevated cholesterol level (0.5%). Plasma lipoproteins were chromatographically separated into four size populations (regions) that were subdivided by density until fractions with single electrophoretic mobilities were obtained. The region III lipoproteins (LDL) contained 80% of plasma cholesterol and were present in the highest concentration of all fractions. Their molecular weight was increased over that of controls so that each particle averaged 1.8 times the number of cholesteryl ester molecules as did control LDL. Region II lipoproteins, a heterogeneous group, were present in next highest concentration. Most were cholesteryl ester-rich, beta-migrating lipoproteins that overlapped the VLDL and LDL density ranges; apoB was the predominant apoprotein. One region II subfraction had pre beta 2 migration and the density range. 1.050 less than d less than 1.10. Another subfraction, cholesteryl ester-rich VLDL including only about 1% of plasma cholesterol, had pre beta 1 migration and apoB and apoC as the predominant apoproteins with no apoprotein E. Region I lipoproteins were larger sized, slow beta-migrating cholesteryl ester-rich VLDL that included 5% of plasma cholesterol. ApoB and apoE were the predominant apoproteins. Region IV lipoproteins (HDL) contained 4% of the plasma cholesterol; their concentration was decreased to about 1/3 of the control level. Atherogenic features of the diet-induced dyslipoproteinemia included the increased plasma concentrations and cholesteryl ester contents of the region I, II, and III lipoproteins in addition to the decreased HDL concentration.", "contents": "Study of the atherogenic dyslipoproteinemia induced by dietary cholesterol in rhesus monekys (Macaca mulatta). Hypercholesterolemia was induced in adult male rhesus monkeys with a high-fat diet containing an elevated cholesterol level (0.5%). Plasma lipoproteins were chromatographically separated into four size populations (regions) that were subdivided by density until fractions with single electrophoretic mobilities were obtained. The region III lipoproteins (LDL) contained 80% of plasma cholesterol and were present in the highest concentration of all fractions. Their molecular weight was increased over that of controls so that each particle averaged 1.8 times the number of cholesteryl ester molecules as did control LDL. Region II lipoproteins, a heterogeneous group, were present in next highest concentration. Most were cholesteryl ester-rich, beta-migrating lipoproteins that overlapped the VLDL and LDL density ranges; apoB was the predominant apoprotein. One region II subfraction had pre beta 2 migration and the density range. 1.050 less than d less than 1.10. Another subfraction, cholesteryl ester-rich VLDL including only about 1% of plasma cholesterol, had pre beta 1 migration and apoB and apoC as the predominant apoproteins with no apoprotein E. Region I lipoproteins were larger sized, slow beta-migrating cholesteryl ester-rich VLDL that included 5% of plasma cholesterol. ApoB and apoE were the predominant apoproteins. Region IV lipoproteins (HDL) contained 4% of the plasma cholesterol; their concentration was decreased to about 1/3 of the control level. Atherogenic features of the diet-induced dyslipoproteinemia included the increased plasma concentrations and cholesteryl ester contents of the region I, II, and III lipoproteins in addition to the decreased HDL concentration."}
{"id": "PMID:220354", "title": "The cholesterol turnover, synthesis, and absorption in two sisters with familial hypercholesterolemia (type IIa).", "content": "To explore the mechanisms of the profound plasma cholesterol elevations in familial homozygous hypercholesterolemia (type IIa), cholesterol turnover, sterol balance, cholesterol absorption, and low density lipoprotein studies were carried out under controlled dietary conditions in two sisters (aged 13 and 16). Cholesterol turnover was prolonged. The half-life of the first exponential of the plasma cholesterol specific activity decay curve was double that of normal adults. The rate constants for the removal of cholesterol from pool A (KAA = 0.0652) and for the excretion of cholesterol from the system (Kaa = 0.0197) were less than half of normal. The production rates of cholesterol were low, only 6.30 and 6.86 mg/kg per day as measured by cholesterol turnover and sterol balance techniques, respectively. Fecal neutral steroid and bile acid excretion were 5.22 and 1.64 mg/kg per day, which is remarkably low in comparison to those of normal and heterozygous children. Cholesterol absorption was within the upper limit of the values reported for normal adults. THE HDL cholesterol values were extremely low (27 mg/dl) in contrast to profoundly elevated LDL levels. The fractional catabolic rate of LDL (0.127 per day) and the rate of synthesis and catabolism of apo-LDL (15 mg/kg per day) were low in comparison to previously reported values in homozygotes. These composite data indicated that the definable metabolic defects of these two sisters with homozygous familial hypercholesterolemia were the sluggish clearance of cholesterol from the body coupled with low total body synthesis of cholesterol.", "contents": "The cholesterol turnover, synthesis, and absorption in two sisters with familial hypercholesterolemia (type IIa). To explore the mechanisms of the profound plasma cholesterol elevations in familial homozygous hypercholesterolemia (type IIa), cholesterol turnover, sterol balance, cholesterol absorption, and low density lipoprotein studies were carried out under controlled dietary conditions in two sisters (aged 13 and 16). Cholesterol turnover was prolonged. The half-life of the first exponential of the plasma cholesterol specific activity decay curve was double that of normal adults. The rate constants for the removal of cholesterol from pool A (KAA = 0.0652) and for the excretion of cholesterol from the system (Kaa = 0.0197) were less than half of normal. The production rates of cholesterol were low, only 6.30 and 6.86 mg/kg per day as measured by cholesterol turnover and sterol balance techniques, respectively. Fecal neutral steroid and bile acid excretion were 5.22 and 1.64 mg/kg per day, which is remarkably low in comparison to those of normal and heterozygous children. Cholesterol absorption was within the upper limit of the values reported for normal adults. THE HDL cholesterol values were extremely low (27 mg/dl) in contrast to profoundly elevated LDL levels. The fractional catabolic rate of LDL (0.127 per day) and the rate of synthesis and catabolism of apo-LDL (15 mg/kg per day) were low in comparison to previously reported values in homozygotes. These composite data indicated that the definable metabolic defects of these two sisters with homozygous familial hypercholesterolemia were the sluggish clearance of cholesterol from the body coupled with low total body synthesis of cholesterol."}
{"id": "PMID:220355", "title": "Quantitation of different cells in the epididymal fat pad of the rat.", "content": "To determine the number of adipocytes and cells developing into adipocytes (preadipocytes) in the epididymal fat pad of normal Sprague-Dawley rats, two methods were developed. Liberation of all cells from the tissue was obtained by a combination of lytic enzymes and mechanical treatment with only a limited loss of cell integrity; with large tissue masses, an initial perfusion was necessary. These cells were cultured in medium 199 supplemented with serum, glucose, insulin, a triglyceride emulsion, and methyl cellulose to form a culture medium with high viscosity in which it has been shown that the cells do no multiply. In this medium some of the cells developed into adipocytes and could be recognized and counted. The results show that there are about twice as many preadipocytes as mature adipocytes in the smallest rats examined (about 50 g). With increasing weight and age the mature adipocytes increased while the number of preadipocytes seemed to be constant up to a weight of about 150 g, after which they continuously diminished and could not be found in rats weighing more than 300 g. Here the number of mature fat cells had reached a constant level. These results are consistent with the formation of new preadipocytes up to a rat weight of about 150 g. In normal rats these cells successively fill up with triglyceride and disappear at a body weight of about 300 g when they have been transformed into mature adipocytes. The results are also consistent with the concept that no new adipocytes are formed spontaneously in the adult Sprague-Dawley rat. It was shown, however, that in media without methyl cellulose, isobutylmethylxanthine probably could induce the formation of new adipocytes in the cells isolated from all rats, including the heaviest (oldest). This finding shows that the potential of cells to develop into adipocytes also seems to exist in the adult rat under certain circumstances.", "contents": "Quantitation of different cells in the epididymal fat pad of the rat. To determine the number of adipocytes and cells developing into adipocytes (preadipocytes) in the epididymal fat pad of normal Sprague-Dawley rats, two methods were developed. Liberation of all cells from the tissue was obtained by a combination of lytic enzymes and mechanical treatment with only a limited loss of cell integrity; with large tissue masses, an initial perfusion was necessary. These cells were cultured in medium 199 supplemented with serum, glucose, insulin, a triglyceride emulsion, and methyl cellulose to form a culture medium with high viscosity in which it has been shown that the cells do no multiply. In this medium some of the cells developed into adipocytes and could be recognized and counted. The results show that there are about twice as many preadipocytes as mature adipocytes in the smallest rats examined (about 50 g). With increasing weight and age the mature adipocytes increased while the number of preadipocytes seemed to be constant up to a weight of about 150 g, after which they continuously diminished and could not be found in rats weighing more than 300 g. Here the number of mature fat cells had reached a constant level. These results are consistent with the formation of new preadipocytes up to a rat weight of about 150 g. In normal rats these cells successively fill up with triglyceride and disappear at a body weight of about 300 g when they have been transformed into mature adipocytes. The results are also consistent with the concept that no new adipocytes are formed spontaneously in the adult Sprague-Dawley rat. It was shown, however, that in media without methyl cellulose, isobutylmethylxanthine probably could induce the formation of new adipocytes in the cells isolated from all rats, including the heaviest (oldest). This finding shows that the potential of cells to develop into adipocytes also seems to exist in the adult rat under certain circumstances."}
{"id": "PMID:220357", "title": "Essential fatty acid deficiency and adrenal cortical function in vitro.", "content": "Adrenocortical cells were prepared from rats maintained on essential fatty acid-deficient diets and control litter mates. Cells from control rats had high concentrations of essential fatty acids in the cholesteryl ester fraction of which approximately 22% was arachidonate. In contrast, cells from EFA-deficient rats had only 2.5% arachidonate in the cholesteryl esters, even though the total esterified cholesterol level was comparable to that of controls. In place of the essential fatty acids, the cholesteryl esters of these cells were rich in 20:3(n--9) and 22:3(n--9). When cells from EFA-deficient rats were incubated with ACTH or dibutyryl cyclic AMP, the output of corticosterone was the same as in controls. Also sterol esters were hydrolyzed to the same extent as in controls despite the unusual composition of the fatty acid esters. The phospholipids in both control and EFA-deficient cells contained high levels of arachidonate but were not hydrolyzed in either type of cell during incubation with ACTH or dibutyryl cyclic AMP. The results indicate that high levels of the prostaglandin precursors, namely linoleate and arachidonate, are not a sine qua non for the steroidogenic action of ACTH or cyclic AMP.", "contents": "Essential fatty acid deficiency and adrenal cortical function in vitro. Adrenocortical cells were prepared from rats maintained on essential fatty acid-deficient diets and control litter mates. Cells from control rats had high concentrations of essential fatty acids in the cholesteryl ester fraction of which approximately 22% was arachidonate. In contrast, cells from EFA-deficient rats had only 2.5% arachidonate in the cholesteryl esters, even though the total esterified cholesterol level was comparable to that of controls. In place of the essential fatty acids, the cholesteryl esters of these cells were rich in 20:3(n--9) and 22:3(n--9). When cells from EFA-deficient rats were incubated with ACTH or dibutyryl cyclic AMP, the output of corticosterone was the same as in controls. Also sterol esters were hydrolyzed to the same extent as in controls despite the unusual composition of the fatty acid esters. The phospholipids in both control and EFA-deficient cells contained high levels of arachidonate but were not hydrolyzed in either type of cell during incubation with ACTH or dibutyryl cyclic AMP. The results indicate that high levels of the prostaglandin precursors, namely linoleate and arachidonate, are not a sine qua non for the steroidogenic action of ACTH or cyclic AMP."}
{"id": "PMID:220358", "title": "Distribution of cholesterol and apolipoprotein A-I and A-II in human high density lipoprotein subfractions separated by CsCl equilibrium gradient centrifugation: evidence for HDL subpopulations with differing A-I/A-II molar ratios.", "content": "The purpose of this experiment was to characterize the high density lipoproteins (HDL) as a function of hydrated density. HDL was subfractionated on the basis of hydrated density by CsCl density gradient centrifugation of whole serum or the d 1.063-1.25 g/ml HDL fraction isolated from three men and three women. Apolipoprotein A-I and A-II quantitation by radial immunodiffusion showed that the A-I/A-II ratio varied with the lipoprotein hydrated density. The A-I/A-II molar ratio of HDL lipoproteins banding between d 1.106 and 1.150 g/ml was nearly constant at 2.2 +/- 0.2. In the density range 1.151-1.25 g/ml the A-I/A-II ratio increased as the density increased. On the other hand, in the density range between 1.077 and 1.105 the A-I/A-II ratio increased as the density decreased, ranging from 2.8 +/- 0.5 for the d 1.093-1.105 g/ml fraction to 5.6 +/- 1.3 for the d 1.077-1.082 g/ml fraction. The d 1.063-1.076 g/ml fraction and the d 1.077-1.082 g/ml fractions had comparable A-I/A-II ratios. Serum and the d 1.063-1.25 g/ml HDL fraction exhibited similar trends. The cholesterol/(A-I + A-II) ratio decreased as the density increased in all 12 samples (six serum and six HDL) examined. Gradient gel electrophoresis of the density gradient fractions showed that as the density increased from 1.063 to 1.200 g/ml the apparent molecular weight decreased from 3.9 x 10(5) to 1.1 x 10(5). HDL subfractions with the same hydrated densities had comparable molecular weights and A-I/A-II and cholesterol/(A-I + A-II) ratios when isolated from men or women. HDL contains subpopulations that differ in the A-I/A-II molar ratio.-Cheung, M. C., and J. J. Albers. Distribution of cholesterol and apolipoprotein A-I and A-II in human high density lipoprotein subfractions separated by CsCl equilibrium gradient centrifugation: evidence for HDL subpopulations with differing A-I/A-II molar ratios.", "contents": "Distribution of cholesterol and apolipoprotein A-I and A-II in human high density lipoprotein subfractions separated by CsCl equilibrium gradient centrifugation: evidence for HDL subpopulations with differing A-I/A-II molar ratios. The purpose of this experiment was to characterize the high density lipoproteins (HDL) as a function of hydrated density. HDL was subfractionated on the basis of hydrated density by CsCl density gradient centrifugation of whole serum or the d 1.063-1.25 g/ml HDL fraction isolated from three men and three women. Apolipoprotein A-I and A-II quantitation by radial immunodiffusion showed that the A-I/A-II ratio varied with the lipoprotein hydrated density. The A-I/A-II molar ratio of HDL lipoproteins banding between d 1.106 and 1.150 g/ml was nearly constant at 2.2 +/- 0.2. In the density range 1.151-1.25 g/ml the A-I/A-II ratio increased as the density increased. On the other hand, in the density range between 1.077 and 1.105 the A-I/A-II ratio increased as the density decreased, ranging from 2.8 +/- 0.5 for the d 1.093-1.105 g/ml fraction to 5.6 +/- 1.3 for the d 1.077-1.082 g/ml fraction. The d 1.063-1.076 g/ml fraction and the d 1.077-1.082 g/ml fractions had comparable A-I/A-II ratios. Serum and the d 1.063-1.25 g/ml HDL fraction exhibited similar trends. The cholesterol/(A-I + A-II) ratio decreased as the density increased in all 12 samples (six serum and six HDL) examined. Gradient gel electrophoresis of the density gradient fractions showed that as the density increased from 1.063 to 1.200 g/ml the apparent molecular weight decreased from 3.9 x 10(5) to 1.1 x 10(5). HDL subfractions with the same hydrated densities had comparable molecular weights and A-I/A-II and cholesterol/(A-I + A-II) ratios when isolated from men or women. HDL contains subpopulations that differ in the A-I/A-II molar ratio.-Cheung, M. C., and J. J. Albers. Distribution of cholesterol and apolipoprotein A-I and A-II in human high density lipoprotein subfractions separated by CsCl equilibrium gradient centrifugation: evidence for HDL subpopulations with differing A-I/A-II molar ratios."}
{"id": "PMID:220359", "title": "Changes in plasma very low density and low density lipoprotein content, composition, and size after a fatty meal in normo- and hypertriglyceridemic man.", "content": "Four subfractions of plasma VLDL characterized by decreasing Sf value and LDL were isolated by density gradient preparative ultracentrifugation from normotriglyceridemic (NTG) and hypertriglyceridemic (HTG) (type IV) subjects in the fasting state and after a fatty meal. Chemical analysis and computation of numbers of particles in each fraction showed that the hyperlipidemia of type IV subjects was accounted for by an increase in total numbers of VLDL and a shift in the distribution of VLDL towards particles of larger diameter. Postprandial hyperlipidemia was due to the presence of chylomicron remnants rather than intact chylomicrons, and was accounted for by an increase in particle diameter of the largest VLDL subfraction rather than by an increase in particle numbers. Postprandial hyperlipedemia was accompanied by a shift in the distribution of VLDL towards particles of larger diameter in both NTG and HTG subjects, probably because of competition for the triglyceride-depletion process between chylomicrons and hepatic VLDL. Most chylomicron remnants were removed from the circulation without degradation to smaller VLDL or to LDL, but some remnants were sufficienty small to contribute to smaller VLDL subfractions. The LDL of type IV subjects contained more apoprotein B than those from NTG subjects, and this difference was associated with increases in diameter, molecular weight, density, and the ratio of protein: phospholipid in LDL from type IV subjects. Defective degradation of large VLDL to small VLDL, and of VLDL to LDL may be related to this alteration in apoprotein B content of the lipoproteins in type IV subjects.", "contents": "Changes in plasma very low density and low density lipoprotein content, composition, and size after a fatty meal in normo- and hypertriglyceridemic man. Four subfractions of plasma VLDL characterized by decreasing Sf value and LDL were isolated by density gradient preparative ultracentrifugation from normotriglyceridemic (NTG) and hypertriglyceridemic (HTG) (type IV) subjects in the fasting state and after a fatty meal. Chemical analysis and computation of numbers of particles in each fraction showed that the hyperlipidemia of type IV subjects was accounted for by an increase in total numbers of VLDL and a shift in the distribution of VLDL towards particles of larger diameter. Postprandial hyperlipidemia was due to the presence of chylomicron remnants rather than intact chylomicrons, and was accounted for by an increase in particle diameter of the largest VLDL subfraction rather than by an increase in particle numbers. Postprandial hyperlipedemia was accompanied by a shift in the distribution of VLDL towards particles of larger diameter in both NTG and HTG subjects, probably because of competition for the triglyceride-depletion process between chylomicrons and hepatic VLDL. Most chylomicron remnants were removed from the circulation without degradation to smaller VLDL or to LDL, but some remnants were sufficienty small to contribute to smaller VLDL subfractions. The LDL of type IV subjects contained more apoprotein B than those from NTG subjects, and this difference was associated with increases in diameter, molecular weight, density, and the ratio of protein: phospholipid in LDL from type IV subjects. Defective degradation of large VLDL to small VLDL, and of VLDL to LDL may be related to this alteration in apoprotein B content of the lipoproteins in type IV subjects."}
{"id": "PMID:220360", "title": "Ontogeny of glycerolipid biosynthetic enzymes in swine liver and adipose tissue.", "content": "Enzymes associated with glycerolipid biosynthesis were examined in microsomal fractions of liver and adipose tissue obtained from swine of various ages. Generally, liver glycerophosphate acyltransferase, phosphatidate phosphohydrolase, diglyceride acyltransferase, and choline phosphotransferase activities were substantial at birth but increased 2- to 3-fold by day 14 postpartum, decreased at day 25, then increased at the oldest ages studied (up to 155 days postpartum). In adipose tissue, enzyme activities were low at birth and developed through day 25 in a pattern generally similar to that observed in liver. In contrast to liver, the adipose enzymes were depressed immediately postweaning (day 32) with subsequent recovery. The observed decline in adipose tissue enzyme activities expressed on a tissue basis at older ages was primarily the result of increased adipocyte size, since the activities expressed on a cell basis did not decline as rapidly. In both liver and adipose tissue, phosphatidate was the major glycerolipid synthesized by the microsomal glycerophosphate acyltransferase enzymes at all ages (generally greater than 75%). The ratio of neutral lipids to phospholipids produced by acylation of glycerophosphate was increased when a microsomal--cytosolic preparation was used as a source of enzyme in contrast to a microsomal preparation.", "contents": "Ontogeny of glycerolipid biosynthetic enzymes in swine liver and adipose tissue. Enzymes associated with glycerolipid biosynthesis were examined in microsomal fractions of liver and adipose tissue obtained from swine of various ages. Generally, liver glycerophosphate acyltransferase, phosphatidate phosphohydrolase, diglyceride acyltransferase, and choline phosphotransferase activities were substantial at birth but increased 2- to 3-fold by day 14 postpartum, decreased at day 25, then increased at the oldest ages studied (up to 155 days postpartum). In adipose tissue, enzyme activities were low at birth and developed through day 25 in a pattern generally similar to that observed in liver. In contrast to liver, the adipose enzymes were depressed immediately postweaning (day 32) with subsequent recovery. The observed decline in adipose tissue enzyme activities expressed on a tissue basis at older ages was primarily the result of increased adipocyte size, since the activities expressed on a cell basis did not decline as rapidly. In both liver and adipose tissue, phosphatidate was the major glycerolipid synthesized by the microsomal glycerophosphate acyltransferase enzymes at all ages (generally greater than 75%). The ratio of neutral lipids to phospholipids produced by acylation of glycerophosphate was increased when a microsomal--cytosolic preparation was used as a source of enzyme in contrast to a microsomal preparation."}
{"id": "PMID:220361", "title": "Changes in the concentration of plasma lipoproteins and apoproteins following the administration of Triton WR 1339 to rats.", "content": "Changes in whole plasma and lipoprotien apoprotein concentrations were determined after a single injection of Triton WR 1339 into rats. Concentrations of apoproteins A-I (an activator of lecithin:cholesterol acyl transferase), arginine-rich apoprotein (ARP), and B apoprotein were measured by electroimmunoassay. The content of C-II apoprotein (an activaor of lipoprotein lipase) was estimated by the ability of plasma and lipoprotein fractions to promote hydrolysis of triglyceride in the presence of cow's milk lipase and also by isoelectric focusing on polyacrylamide gels. Apoproteins C-II and A-I were rapidly removed from high density lipoprotein (HDL) after Triton treatment and were recovered in the d 1.21 g/ml infranate fraction. A-I was then totally cleared from the plasma within 10--20 hr after injection. Arginine-rich apoprotein was removed from HDL and also partially cleared from the plasma. The rise in very low density lipoprotein (vldl) apoprotein that followed the removal of apoproteins from HDL was mostly antributed to the B apoprotein, although corresponding smaller increases were observed in VLDL ARP and C apoproteins. The triglyceride:cholesterol, triglyceride:protein, and B:C apoprotein ratios of VLDL more closely resembled nascent rather than plasma VLDL 10 hr after Triton injection. These studies suggest that the detergent may achieve its hyperlipidemic effct by disrupting HDL and thus removing the A-I and C-II proteins from a normal activating environment compirsing VLDL, HDL, and the enzymes. The possible involvement of intact HDL in VLDL catabolism is discussed in relation to other recent reports which also suggest that abnormalities of the VLDL-LDL system may be due to the absence of normal HDL.", "contents": "Changes in the concentration of plasma lipoproteins and apoproteins following the administration of Triton WR 1339 to rats. Changes in whole plasma and lipoprotien apoprotein concentrations were determined after a single injection of Triton WR 1339 into rats. Concentrations of apoproteins A-I (an activator of lecithin:cholesterol acyl transferase), arginine-rich apoprotein (ARP), and B apoprotein were measured by electroimmunoassay. The content of C-II apoprotein (an activaor of lipoprotein lipase) was estimated by the ability of plasma and lipoprotein fractions to promote hydrolysis of triglyceride in the presence of cow's milk lipase and also by isoelectric focusing on polyacrylamide gels. Apoproteins C-II and A-I were rapidly removed from high density lipoprotein (HDL) after Triton treatment and were recovered in the d 1.21 g/ml infranate fraction. A-I was then totally cleared from the plasma within 10--20 hr after injection. Arginine-rich apoprotein was removed from HDL and also partially cleared from the plasma. The rise in very low density lipoprotein (vldl) apoprotein that followed the removal of apoproteins from HDL was mostly antributed to the B apoprotein, although corresponding smaller increases were observed in VLDL ARP and C apoproteins. The triglyceride:cholesterol, triglyceride:protein, and B:C apoprotein ratios of VLDL more closely resembled nascent rather than plasma VLDL 10 hr after Triton injection. These studies suggest that the detergent may achieve its hyperlipidemic effct by disrupting HDL and thus removing the A-I and C-II proteins from a normal activating environment compirsing VLDL, HDL, and the enzymes. The possible involvement of intact HDL in VLDL catabolism is discussed in relation to other recent reports which also suggest that abnormalities of the VLDL-LDL system may be due to the absence of normal HDL."}
{"id": "PMID:220364", "title": "Characterization of the specific binding of prolactin to binding sites in the seminal vesicle of the rat.", "content": "The binding of ovine prolactin to the seminal vesicles of the rat has been characterized and found to be a saturable process, dependent upon time, temperature, protein concentration of the seminal vesicle and divalent ions. Its specificity was similar to that reported for prolactin binding to other organ preparations. Time and temperature studies of the specific binding revealed that equilibrium was reached after 16 h at 5 degrees C or 4 h at 19 degrees C. Nonspecific binding was also dependent on time and temperature. This parameter has been reported to comprise up to 70% of the total binding to various organ-binding sites, but it fell to below 20% after 48 h at 19 degrees C, thus demonstrating the high degree of specificity required of target organ receptors. From degradation studies it was evident that no damage occurred to the free hormone during incubation for up to 70 h at 5 degrees C or 16 h at 19 degrees C. However, there seems to be a difference in the susceptibility of bound and free ovine prolactin to damage during incubation: after 40 h at 19 degrees C the hormone in the supernatant fraction had lost 85% of its binding ability, whereas a high level of specific binding was evident in the pellet. A Scatchard plot of competitive binding studies revealed two classes of binding sites, of which the high-affinity, low-capacity site was similar to that reported previously and consistent with a physiological receptor for prolactin in the seminal vesicle of the rat.", "contents": "Characterization of the specific binding of prolactin to binding sites in the seminal vesicle of the rat. The binding of ovine prolactin to the seminal vesicles of the rat has been characterized and found to be a saturable process, dependent upon time, temperature, protein concentration of the seminal vesicle and divalent ions. Its specificity was similar to that reported for prolactin binding to other organ preparations. Time and temperature studies of the specific binding revealed that equilibrium was reached after 16 h at 5 degrees C or 4 h at 19 degrees C. Nonspecific binding was also dependent on time and temperature. This parameter has been reported to comprise up to 70% of the total binding to various organ-binding sites, but it fell to below 20% after 48 h at 19 degrees C, thus demonstrating the high degree of specificity required of target organ receptors. From degradation studies it was evident that no damage occurred to the free hormone during incubation for up to 70 h at 5 degrees C or 16 h at 19 degrees C. However, there seems to be a difference in the susceptibility of bound and free ovine prolactin to damage during incubation: after 40 h at 19 degrees C the hormone in the supernatant fraction had lost 85% of its binding ability, whereas a high level of specific binding was evident in the pellet. A Scatchard plot of competitive binding studies revealed two classes of binding sites, of which the high-affinity, low-capacity site was similar to that reported previously and consistent with a physiological receptor for prolactin in the seminal vesicle of the rat."}
{"id": "PMID:220365", "title": "Acetylcholine stimulates growth hormone secretion, phosphatidyl inositol labelling, 45Ca2+ efflux and cyclic GMP accumulation in bovine anterior pituitary glands.", "content": "Acetylcholine (25 micromol/l) in the presence of the choline esterase inhibitor physostigmine (67 micromol/l) increased the release of growth hormone and efflux of 45Ca2+ from perifused bovine pituitary slices; the time taken for the maximal response to occur was the same. In batch incubations, acetylcholine (1 micromol/l--1 mmol/l) increased pituitary cyclic GMP concentrations in the pituitary gland within 2 min, and increased incorporation of [3H]inositol and [32P]phosphate into pituitary phosphatidyl inositol within 15 min. Cyclic AMP concentrations were not significantly changed 2 or 5 min after acetylcholine addition. All the tissue responses were inhibited by prior exposure of the tissue to atropine (1 micromol/l) but not by tubocurarine (10 micromol/l--1mmol/l), indicating that the responses were mediated by receptors of the muscarinic type. The similarities between these responses and those to known hypothalamic hypophysiotrophic hormones are discussed.", "contents": "Acetylcholine stimulates growth hormone secretion, phosphatidyl inositol labelling, 45Ca2+ efflux and cyclic GMP accumulation in bovine anterior pituitary glands. Acetylcholine (25 micromol/l) in the presence of the choline esterase inhibitor physostigmine (67 micromol/l) increased the release of growth hormone and efflux of 45Ca2+ from perifused bovine pituitary slices; the time taken for the maximal response to occur was the same. In batch incubations, acetylcholine (1 micromol/l--1 mmol/l) increased pituitary cyclic GMP concentrations in the pituitary gland within 2 min, and increased incorporation of [3H]inositol and [32P]phosphate into pituitary phosphatidyl inositol within 15 min. Cyclic AMP concentrations were not significantly changed 2 or 5 min after acetylcholine addition. All the tissue responses were inhibited by prior exposure of the tissue to atropine (1 micromol/l) but not by tubocurarine (10 micromol/l--1mmol/l), indicating that the responses were mediated by receptors of the muscarinic type. The similarities between these responses and those to known hypothalamic hypophysiotrophic hormones are discussed."}
{"id": "PMID:220366", "title": "Evidence that both long-acting thyroid stimulator and long-acting thyroid stimulator-protector stimulate the human thyroid gland.", "content": "Thyroid-stimulating immunoglobulins were prepared from two potent sera, one contained long-acting thyroid stimulator (LATS) and the other contained both LATS and LATS-protector (LATS-P). The potencies of the immunoglobulin G (IgG) preparations were estimated in the McKenzie assay. The accumulation of cyclic AMP in mouse thyroid lobes was stimulated only by LATS--IgG; LATS-P--IgG was inactive. In contrast, both LATS-IgG and LATS-P--IgG were equally effective in slices of human thyroid.", "contents": "Evidence that both long-acting thyroid stimulator and long-acting thyroid stimulator-protector stimulate the human thyroid gland. Thyroid-stimulating immunoglobulins were prepared from two potent sera, one contained long-acting thyroid stimulator (LATS) and the other contained both LATS and LATS-protector (LATS-P). The potencies of the immunoglobulin G (IgG) preparations were estimated in the McKenzie assay. The accumulation of cyclic AMP in mouse thyroid lobes was stimulated only by LATS--IgG; LATS-P--IgG was inactive. In contrast, both LATS-IgG and LATS-P--IgG were equally effective in slices of human thyroid."}
{"id": "PMID:220367", "title": "Ontogeny and control of prolactin receptors in the mammary gland and liver of virgin, pregnant and lactating rats.", "content": "Prolactin receptors were identified and partially characterized in the mammary gland of the rat. The binding of 125I-labelled ovine prolactin to a subcellular particulate fraction of rat mammary gland decreased between days 30 and 100 of age. Over the same period, binding to the liver increased and there was a significant negative correlation between prolactin binding in the two tissues. Binding to the mammary gland was low during pregnancy, increased in early lactation and declined after the litters were weaned. Binding to the liver was lower during lactation than during pregnancy or the period after weaning suggesting that tissue-specific factors may operate in the control of this receptor. In virgin rats, prolactin binding by the mammary gland was increased by oestrogen. This effect was blocked by hypophysectomy and partially restored by replacement therapy with prolactin. Hypothyroidism and treatment with progesterone also reduced the response to oestrogen. The maintenance of prolactin binding by the mammary gland of lactating rats depends on the presence of the ovaries and pituitary, thyroid and adrenal glands. Examination of the ratio epithelium: stroma suggests that prolactin acts by increasing the number of epithelial cells in the mammary gland and that thyroid, adrenal and ovarian hormones modulate the number of receptors per cell.", "contents": "Ontogeny and control of prolactin receptors in the mammary gland and liver of virgin, pregnant and lactating rats. Prolactin receptors were identified and partially characterized in the mammary gland of the rat. The binding of 125I-labelled ovine prolactin to a subcellular particulate fraction of rat mammary gland decreased between days 30 and 100 of age. Over the same period, binding to the liver increased and there was a significant negative correlation between prolactin binding in the two tissues. Binding to the mammary gland was low during pregnancy, increased in early lactation and declined after the litters were weaned. Binding to the liver was lower during lactation than during pregnancy or the period after weaning suggesting that tissue-specific factors may operate in the control of this receptor. In virgin rats, prolactin binding by the mammary gland was increased by oestrogen. This effect was blocked by hypophysectomy and partially restored by replacement therapy with prolactin. Hypothyroidism and treatment with progesterone also reduced the response to oestrogen. The maintenance of prolactin binding by the mammary gland of lactating rats depends on the presence of the ovaries and pituitary, thyroid and adrenal glands. Examination of the ratio epithelium: stroma suggests that prolactin acts by increasing the number of epithelial cells in the mammary gland and that thyroid, adrenal and ovarian hormones modulate the number of receptors per cell."}
{"id": "PMID:220373", "title": "Suppression of serum levels of luteinizing hormone by short- and long-loop negative feedback in ovariectomized women.", "content": "The suppressive effects of short- and long-loop negative feedback on serum levels of LH were assessed after administration of human chorionic gonadotrophin (HCG) and conjugated oestrogens. Fourteen ovariectomized women were injected intravenously with 5 mg conjugated oestrogens, eight of these patients were also given an intramuscular injection of 10,000 i.u. HCG 8 h later, while the other six patients were given a control injection of 0.9% saline. The serum levels of LH decreased by similar amounts in both groups of women. Thirteen other ovariectomized women were initially injected with 10,000 i.u. HCG, i.m., seven of these patients were also given an i.v. ijection of 5 mg conjugated oestrogens 8 h later, while the remaining six patients received a control injection of 0.9% saline. The results showed that conjugated estrogens could further supress the serum level of LH which had been reduced by prior HCG treatment. In six ovariectomized women who received i.m. saline injections at the start of the experiment and 8 h later, the serum levels of LH did not change significantly. It is concluded that the suppression of the serum concentrations of LH by long-loop negative feedback after administration of 5 mg conjugated oestrogens is greater than that by short-loop negative feedback after treatment with 10,000 i.u. HCG.", "contents": "Suppression of serum levels of luteinizing hormone by short- and long-loop negative feedback in ovariectomized women. The suppressive effects of short- and long-loop negative feedback on serum levels of LH were assessed after administration of human chorionic gonadotrophin (HCG) and conjugated oestrogens. Fourteen ovariectomized women were injected intravenously with 5 mg conjugated oestrogens, eight of these patients were also given an intramuscular injection of 10,000 i.u. HCG 8 h later, while the other six patients were given a control injection of 0.9% saline. The serum levels of LH decreased by similar amounts in both groups of women. Thirteen other ovariectomized women were initially injected with 10,000 i.u. HCG, i.m., seven of these patients were also given an i.v. ijection of 5 mg conjugated oestrogens 8 h later, while the remaining six patients received a control injection of 0.9% saline. The results showed that conjugated estrogens could further supress the serum level of LH which had been reduced by prior HCG treatment. In six ovariectomized women who received i.m. saline injections at the start of the experiment and 8 h later, the serum levels of LH did not change significantly. It is concluded that the suppression of the serum concentrations of LH by long-loop negative feedback after administration of 5 mg conjugated oestrogens is greater than that by short-loop negative feedback after treatment with 10,000 i.u. HCG."}
{"id": "PMID:220374", "title": "A rapid and specific method for separation of bound and free antigen in radioimmunoassay systems.", "content": "This communication reports a method for increasing the speed of separation of bound and free antigen in radioimmunoassay systems with no loss in the specificity of binding. The technique uses a mixture of second antibody and polyethylene glycol. It is not species or antibody specific, and systems using specific first antibodies from rabbit, goat or sheep are all functional. Results for the assay of parathyrin, calcitonin and corticotropin are described here, although the system has been shown to work for triiodothyronine, thyroxin, thyrotropin, thyroxine binding globulin and transferrin. The time taken for the reaction between first and second antibody is in the order of seconds, and the stability of the complex is unchanged over a period of hours.", "contents": "A rapid and specific method for separation of bound and free antigen in radioimmunoassay systems. This communication reports a method for increasing the speed of separation of bound and free antigen in radioimmunoassay systems with no loss in the specificity of binding. The technique uses a mixture of second antibody and polyethylene glycol. It is not species or antibody specific, and systems using specific first antibodies from rabbit, goat or sheep are all functional. Results for the assay of parathyrin, calcitonin and corticotropin are described here, although the system has been shown to work for triiodothyronine, thyroxin, thyrotropin, thyroxine binding globulin and transferrin. The time taken for the reaction between first and second antibody is in the order of seconds, and the stability of the complex is unchanged over a period of hours."}
{"id": "PMID:220376", "title": "4-Aminopyridine and the early outward current of sheep cardiac Purkinje fibers.", "content": "We have studied the effects of the potassium-blocking agent 4-aminopyridine (4-AP) on the action potential and membrane currents of the sheep cardiac Purkinje fiber. 4-AP slowed the rate of phase 1 repolarization and shifted the plateau of the action potential to less negative potentials. In the presence of 4-AP, the substitution of sodium methylsulfate or methanesulfonate for the NaCl of Tyrode's solution further slowed the rate of phase 1 repolarization, even though chloride replacement has no effect on the untreated preparation. In voltage clamp experiments, 4-AP rapidly and reversibly reduced the early peak of outward current that is seen when the Purkinje fiber membrane is voltage-clamped to potentials positive to -20 mV. In addition, 4-AP reduced the steady outward current seen at the end of clamp steps positive to -40 mV. 4-AP did not appear to change the slow inward current observed over the range of -60 to -40 mV, nor did it greatly change the current tails that have been used as a measure of the slow inward conductance at more positive potentials. 4-AP did not block the inward rectifying potassium currents, IK1 and IK2. A phasic outward current component that was insensitive to 4-AP was reduced by chloride replacement. We conclude that the early outward current has two components: a chloride-sensitive component plus a 4-AP-sensitive component. Since a portion of the steady-state current was sensitive to 4-AP, the early outward current either does not fully inactivate or  4-AP blocks a component of time-independent background current.", "contents": "4-Aminopyridine and the early outward current of sheep cardiac Purkinje fibers. We have studied the effects of the potassium-blocking agent 4-aminopyridine (4-AP) on the action potential and membrane currents of the sheep cardiac Purkinje fiber. 4-AP slowed the rate of phase 1 repolarization and shifted the plateau of the action potential to less negative potentials. In the presence of 4-AP, the substitution of sodium methylsulfate or methanesulfonate for the NaCl of Tyrode's solution further slowed the rate of phase 1 repolarization, even though chloride replacement has no effect on the untreated preparation. In voltage clamp experiments, 4-AP rapidly and reversibly reduced the early peak of outward current that is seen when the Purkinje fiber membrane is voltage-clamped to potentials positive to -20 mV. In addition, 4-AP reduced the steady outward current seen at the end of clamp steps positive to -40 mV. 4-AP did not appear to change the slow inward current observed over the range of -60 to -40 mV, nor did it greatly change the current tails that have been used as a measure of the slow inward conductance at more positive potentials. 4-AP did not block the inward rectifying potassium currents, IK1 and IK2. A phasic outward current component that was insensitive to 4-AP was reduced by chloride replacement. We conclude that the early outward current has two components: a chloride-sensitive component plus a 4-AP-sensitive component. Since a portion of the steady-state current was sensitive to 4-AP, the early outward current either does not fully inactivate or  4-AP blocks a component of time-independent background current."}
{"id": "PMID:220377", "title": "Thyroid thermogenesis in adult rat hepatocytes in primary monolayer culture: direct action of thyroid hormone in vitro.", "content": "We have studied the effect of 3,5,3'-triiodothyronine (T3) on the respiration of adult rat hepatocytes in primary monolayer culture prepared from hypothyroid rat liver. After addition of T3 to the culture medium at a concentration of 2 x 10(-7) M, oxygen consumption of the cultured cells increased detectably at 24 h and was maximal at 72--96 h, relative to control cultures (38.0 +/- 1.8 vs. 25.0 +/- 1.5 microliter/h.mg protein). The thyroid-responsive enzymes, Na+ + K+-activated adenosine triphosphatase (NaK-ATPase) and alpha-glycerophosphate dehydrogenase (GPD), each exhibited increased activity in response to T3, in parallel with the change in oxygen consumption, whereas the activity of Mg-dependent ATPase was unaffected. These responses to T3 were dose dependent over similar concentration ranges, the half-maximal response for each occurring at ca 8 x 10(-10) M. In thyroid-treated cells, the observed increase in respiration was almost completely (90%) inhibited after addition of ouabain (10(-3) M) to the culture medium. It was found also that a 4-h exposure of the cultured hepatocytes to T3 was sufficient to elicit a significant thermogenic response, measured at a time (48 h later) when T3 was no longer present in the medium. The response to T3 occurred in fully defined culture medium and was independent of the presence or absence of hypothyroid rat serum, corticosterone, or insulin, and cellular ATP was unaffected by T3 in concentrations up to 2 x 10(-7) M. The findings document that adult rat hepatocytes in primary monolayer culture respond directly to thyroid hormone; the increases in respiration and NaK-ATPase activity elicited by T3 were cotemporal and apparently coordinate.", "contents": "Thyroid thermogenesis in adult rat hepatocytes in primary monolayer culture: direct action of thyroid hormone in vitro. We have studied the effect of 3,5,3'-triiodothyronine (T3) on the respiration of adult rat hepatocytes in primary monolayer culture prepared from hypothyroid rat liver. After addition of T3 to the culture medium at a concentration of 2 x 10(-7) M, oxygen consumption of the cultured cells increased detectably at 24 h and was maximal at 72--96 h, relative to control cultures (38.0 +/- 1.8 vs. 25.0 +/- 1.5 microliter/h.mg protein). The thyroid-responsive enzymes, Na+ + K+-activated adenosine triphosphatase (NaK-ATPase) and alpha-glycerophosphate dehydrogenase (GPD), each exhibited increased activity in response to T3, in parallel with the change in oxygen consumption, whereas the activity of Mg-dependent ATPase was unaffected. These responses to T3 were dose dependent over similar concentration ranges, the half-maximal response for each occurring at ca 8 x 10(-10) M. In thyroid-treated cells, the observed increase in respiration was almost completely (90%) inhibited after addition of ouabain (10(-3) M) to the culture medium. It was found also that a 4-h exposure of the cultured hepatocytes to T3 was sufficient to elicit a significant thermogenic response, measured at a time (48 h later) when T3 was no longer present in the medium. The response to T3 occurred in fully defined culture medium and was independent of the presence or absence of hypothyroid rat serum, corticosterone, or insulin, and cellular ATP was unaffected by T3 in concentrations up to 2 x 10(-7) M. The findings document that adult rat hepatocytes in primary monolayer culture respond directly to thyroid hormone; the increases in respiration and NaK-ATPase activity elicited by T3 were cotemporal and apparently coordinate."}
{"id": "PMID:220378", "title": "Phagolysosome formation, cyclic adenosine 3':5'-monophosphate and the fate of Salmonella typhimurium within mouse peritoneal macrophages.", "content": "Salmonella typhimurium did not inhibit fusion of lysosomes with the phagocytic vacuoles in infected macrophages and caused no increase in cyclic adenosine 3':5'-monophosphate. Glutaraldehyde-killed bacteria showed rapid ultrastructural degeneration within the phagolysosomes. In contrast, untreated bacteria were resistant to digestion by lysosomal enzymes. Intracellular survival of this species appears to depend on resistance to, and not evasion of, lysosomal enzymes.", "contents": "Phagolysosome formation, cyclic adenosine 3':5'-monophosphate and the fate of Salmonella typhimurium within mouse peritoneal macrophages. Salmonella typhimurium did not inhibit fusion of lysosomes with the phagocytic vacuoles in infected macrophages and caused no increase in cyclic adenosine 3':5'-monophosphate. Glutaraldehyde-killed bacteria showed rapid ultrastructural degeneration within the phagolysosomes. In contrast, untreated bacteria were resistant to digestion by lysosomal enzymes. Intracellular survival of this species appears to depend on resistance to, and not evasion of, lysosomal enzymes."}
{"id": "PMID:220379", "title": "Phagosome-lysosome fusion and cyclic adenosine 3':5'-monophosphate in macrophages infected with Mycobacterium microti, Mycobacterium bovis BCG or Mycobacterium lepraemurium.", "content": "When ingested by mouse peritoneal macrophage monolayers, live Mycobacterium microti caused a sustained increase in monolayer cyclic AMP content and fusion of lysosomes with the bacterium-containing phagosomes was impaired. Ingested live M. bovis BCG caused a transient increase in cyclic AMP and the defect in phagolysosome formation was less pronounced. Dead mycobacteria and live M. lepraemurium neither enhanced monolayer cyclic AMP content nor inhibited phagolysosome formation. Mycobacterium microti and BCG exceeded M. lepraemurium in cyclic AMP-synthesizing activity in vitro but the question of whether bacterial cyclic AMP contributed substantially to the increments in infected macrophages was not resolved. Antibody-coated BCG retained the ability to synthesize cyclic AMP and to enhance monolayer cyclic AMP but lost the ability to inhibit phagolysosome formation in macrophages, The observations are discussed in terms of possible control of phagolysosome formation by cyclic nucleotides.", "contents": "Phagosome-lysosome fusion and cyclic adenosine 3':5'-monophosphate in macrophages infected with Mycobacterium microti, Mycobacterium bovis BCG or Mycobacterium lepraemurium. When ingested by mouse peritoneal macrophage monolayers, live Mycobacterium microti caused a sustained increase in monolayer cyclic AMP content and fusion of lysosomes with the bacterium-containing phagosomes was impaired. Ingested live M. bovis BCG caused a transient increase in cyclic AMP and the defect in phagolysosome formation was less pronounced. Dead mycobacteria and live M. lepraemurium neither enhanced monolayer cyclic AMP content nor inhibited phagolysosome formation. Mycobacterium microti and BCG exceeded M. lepraemurium in cyclic AMP-synthesizing activity in vitro but the question of whether bacterial cyclic AMP contributed substantially to the increments in infected macrophages was not resolved. Antibody-coated BCG retained the ability to synthesize cyclic AMP and to enhance monolayer cyclic AMP but lost the ability to inhibit phagolysosome formation in macrophages, The observations are discussed in terms of possible control of phagolysosome formation by cyclic nucleotides."}
{"id": "PMID:220380", "title": "Anatomical relationships between the ventral mesencephalic tegmentum--a 10 region and the locus coeruleus as demonstrated by anterograde and retrograde tracing techniques.", "content": "We have searched for anatomical connections between the ventral mesencephalic tegmentum (VMT), including the dopaminergic cell group A10 and the locus coeruleus (LC) region. Tritiated leucine (120--220 nl) and horseradish peroxidase delivered by electrophoresis were injected in the VMT-A10 region. We have demonstrated, on the one hand bilateral projections from the VMT-A10 region to LC, and on the other hand a possible contralateral projection from LC to VMT-A10 region. These relationships, reported for the first time may have some important functional significance.", "contents": "Anatomical relationships between the ventral mesencephalic tegmentum--a 10 region and the locus coeruleus as demonstrated by anterograde and retrograde tracing techniques. We have searched for anatomical connections between the ventral mesencephalic tegmentum (VMT), including the dopaminergic cell group A10 and the locus coeruleus (LC) region. Tritiated leucine (120--220 nl) and horseradish peroxidase delivered by electrophoresis were injected in the VMT-A10 region. We have demonstrated, on the one hand bilateral projections from the VMT-A10 region to LC, and on the other hand a possible contralateral projection from LC to VMT-A10 region. These relationships, reported for the first time may have some important functional significance."}
{"id": "PMID:220381", "title": "Contribution of the locus coeruleus to the adrenergic innervation of the rat spinal cord: a biochemical study.", "content": "The possible existence and magnitude of a noradrenergic innervation from the locus coeruleus (LC) to the spinal cord was investigated in the rat with various techniques. Horseradish peroxidase, injected into the lumbar spinal cord produced heavy labelling of presumably noradrenaline (NA)-containing neurons in the ventral region of the LC, while cells in the dorsal region of the LC were only lightly labelled. The effects of electrothermic destruction and electrical stimulation of the LC on levels of NA in various parts of the spinal cord, the cerebral cortex and the hippocampus were studied. Fourteen days after unilateral destruction of the LC there were decreases in NA levels of about 85% in the cerebral cortex and hippocampus and of about 15% in the cervical and thoracic segments of the spinal cord (ipsilateral versus contralateral). Fourteen days after bilateral lesioning of the LC significant decreases (about 25%) in NA levels were observed in all spinal cord segments. Unilateral stimulation in or near the LC induced decreases of NA levels in all areas of the central nervous system investigated. In this experiment the levels of NA in the spinal cord were significantly lowered in the ipsilateral cervical (16%), thoracic (12%) and lumbar/sacral (15%) segments of the spinal cord. These findings together indicate that a small part (no more than 30%) of the NA levels in the rat spinal cord are dependent upon the integrity and activity of NA-containing neurons of the predominantly ipsilaterally localized LC.", "contents": "Contribution of the locus coeruleus to the adrenergic innervation of the rat spinal cord: a biochemical study. The possible existence and magnitude of a noradrenergic innervation from the locus coeruleus (LC) to the spinal cord was investigated in the rat with various techniques. Horseradish peroxidase, injected into the lumbar spinal cord produced heavy labelling of presumably noradrenaline (NA)-containing neurons in the ventral region of the LC, while cells in the dorsal region of the LC were only lightly labelled. The effects of electrothermic destruction and electrical stimulation of the LC on levels of NA in various parts of the spinal cord, the cerebral cortex and the hippocampus were studied. Fourteen days after unilateral destruction of the LC there were decreases in NA levels of about 85% in the cerebral cortex and hippocampus and of about 15% in the cervical and thoracic segments of the spinal cord (ipsilateral versus contralateral). Fourteen days after bilateral lesioning of the LC significant decreases (about 25%) in NA levels were observed in all spinal cord segments. Unilateral stimulation in or near the LC induced decreases of NA levels in all areas of the central nervous system investigated. In this experiment the levels of NA in the spinal cord were significantly lowered in the ipsilateral cervical (16%), thoracic (12%) and lumbar/sacral (15%) segments of the spinal cord. These findings together indicate that a small part (no more than 30%) of the NA levels in the rat spinal cord are dependent upon the integrity and activity of NA-containing neurons of the predominantly ipsilaterally localized LC."}
{"id": "PMID:220385", "title": "Neuropathy, amyloidosis, and monoclonal gammopathy.", "content": "Three cases of neuropathy with monoclonal gammopathy and amyloid deposits in peripheral nerves are described. They appeared to present a benign gammopathy because of the duration of the neuropathy in the absence of any clinical or biological sign of myeloma or macroglobulinaemia. The pathological abnormality found in the sural nerves of the three patients was characterised by a marked loss of myelinated and unmyelinated nerve fibres because of active axonal degeneration with Wallerian degeneration. The most striking feature in all three cases was the finding of deposits identified as an accumulation of microfibrils.", "contents": "Neuropathy, amyloidosis, and monoclonal gammopathy. Three cases of neuropathy with monoclonal gammopathy and amyloid deposits in peripheral nerves are described. They appeared to present a benign gammopathy because of the duration of the neuropathy in the absence of any clinical or biological sign of myeloma or macroglobulinaemia. The pathological abnormality found in the sural nerves of the three patients was characterised by a marked loss of myelinated and unmyelinated nerve fibres because of active axonal degeneration with Wallerian degeneration. The most striking feature in all three cases was the finding of deposits identified as an accumulation of microfibrils."}
{"id": "PMID:220386", "title": "Effect of temperature on neuromuscular transmission in the Eaton-Lambert syndrome.", "content": "A patient with the Eaton-Lambert syndrome is described in whom no associated condition was discovered. There was clinical and electrical evidence that the defect in neuromuscular transmission became more severe as local temperature was raised.", "contents": "Effect of temperature on neuromuscular transmission in the Eaton-Lambert syndrome. A patient with the Eaton-Lambert syndrome is described in whom no associated condition was discovered. There was clinical and electrical evidence that the defect in neuromuscular transmission became more severe as local temperature was raised."}
{"id": "PMID:220388", "title": "Multiple sclerosis-associated agent. Failure of MS brain and serum to depress the polymorph count in normal mice and mice inoculated with cells containing C/type particles.", "content": "The groups that originally reported and confirmed the demonstration of a multiple sclerosis associated agent (MSAA) are now, along with others, unable to reproduce this effect. In view of this confusion and the potential importance of this work for multiple sclerosis (MS) we have done a strict double-blind trial using larger groups of mice (10) and counting more cells (900) than in previous reports to offset the high variability of mouse polymorphonuclear neutrophil (PMN) counts. Sera from 5 active MS patients and 4 normal subjects were tested in mice, half of which had previously been injected with PAM line cells (containing C-type particles and subject to reduced cell yield when cultured with MS brain extract). No significant PMN depression was found in either MS or normals on any basis of comparison. However, a significant depression was seen following PAM cell injection irrespective of serum origin. Higher counting accuracy did not reduce PMN variability. A single MS brain specimen was also without effect. consequently we have been unable to confirm the existence of an MSAA as defined by PMN depression in mice.", "contents": "Multiple sclerosis-associated agent. Failure of MS brain and serum to depress the polymorph count in normal mice and mice inoculated with cells containing C/type particles. The groups that originally reported and confirmed the demonstration of a multiple sclerosis associated agent (MSAA) are now, along with others, unable to reproduce this effect. In view of this confusion and the potential importance of this work for multiple sclerosis (MS) we have done a strict double-blind trial using larger groups of mice (10) and counting more cells (900) than in previous reports to offset the high variability of mouse polymorphonuclear neutrophil (PMN) counts. Sera from 5 active MS patients and 4 normal subjects were tested in mice, half of which had previously been injected with PAM line cells (containing C-type particles and subject to reduced cell yield when cultured with MS brain extract). No significant PMN depression was found in either MS or normals on any basis of comparison. However, a significant depression was seen following PAM cell injection irrespective of serum origin. Higher counting accuracy did not reduce PMN variability. A single MS brain specimen was also without effect. consequently we have been unable to confirm the existence of an MSAA as defined by PMN depression in mice."}
{"id": "PMID:220390", "title": "Analysis of the major lipid classes in human peripheral nerve biopsies. Age group differences and abnormalities of ganglioside level in perhexiline maleate therapy.", "content": "We report here the results of a simple and reproducible technique which can be used in semi-routine analysis of peripheral nerve biopsy specimens, so as to have a quantitative analysis of the major lipid classes, i.e. cholesterol, cerebrosides, ethanolamine phospholipids, phosphatidyl-choline, phosphatidyl-serine + phosphatidylinositol, sphingomyelin and gangliosides. Glycolipid hexoses, cholesterol and total phospholipids have been compared in different age groups. Although all lipid classes increased from the younger to the older age group, the molar ratio of cholesterol to phospholipid differed less than the glycolipid to phospholipid ratio. Both increased significantly, even between age group 10--16 and older patients (36, 54, 61, 68, 72 and 73 years old). Although individual variations in lipid content are noteworthy, it must be emphasized that evolution with age of the lipid composition must be taken into account. Furthermore, this study confirms and extends earlier findings of increased ganglioside levels in some cases of peripheral neuropathies observed during perhexiline maleate therapy where characteristic lipid-like polymorphous inclusions have been demonstrated.", "contents": "Analysis of the major lipid classes in human peripheral nerve biopsies. Age group differences and abnormalities of ganglioside level in perhexiline maleate therapy. We report here the results of a simple and reproducible technique which can be used in semi-routine analysis of peripheral nerve biopsy specimens, so as to have a quantitative analysis of the major lipid classes, i.e. cholesterol, cerebrosides, ethanolamine phospholipids, phosphatidyl-choline, phosphatidyl-serine + phosphatidylinositol, sphingomyelin and gangliosides. Glycolipid hexoses, cholesterol and total phospholipids have been compared in different age groups. Although all lipid classes increased from the younger to the older age group, the molar ratio of cholesterol to phospholipid differed less than the glycolipid to phospholipid ratio. Both increased significantly, even between age group 10--16 and older patients (36, 54, 61, 68, 72 and 73 years old). Although individual variations in lipid content are noteworthy, it must be emphasized that evolution with age of the lipid composition must be taken into account. Furthermore, this study confirms and extends earlier findings of increased ganglioside levels in some cases of peripheral neuropathies observed during perhexiline maleate therapy where characteristic lipid-like polymorphous inclusions have been demonstrated."}
{"id": "PMID:220391", "title": "Short-term effects of prednisolone on neuromuscular transmission in normal rats and those with experimental autoimmune myasthenia gravis.", "content": "Electrophysiological investigations of the effects of bath-applied prednisolone at the neuromuscular junction were performed in muscles from normal rats and rats with experimental autoimmune myasthenia gravis (EAMG). In muscles from both groups, prednisolone reversible and significantly depressed the amplitudes of minature end-plate potentials (MEPPs), end-plate potentials (EPPs) and indirectly elicited action potentials (APs) without affecting resting membrane potentials. Prednisolone also caused a significant reduction in EPP rise time to peak and half-decay time while markedly increasing MEPP frequency and AP rise time to peak and duration. These effects were shown to be dose-dependent. The percentage decrease in amplitude after prednisolone perfusion was similar for EPPs and MEPPs, indicating that the depressive effect of prednisolone at the junction is postsynaptic. In all of the parameters studied, the percentage effect of prednisolone was the same in EAMG and normal preparations. No stimulus-linked repetitive EPPs or APs were observed after prednisolone. It is concluded that prednisolone has a depressive effect on neuromuscular transmission, but that this occurs only at high concentrations of the drug which are not achieved during the treatment of myasthenia gravis.", "contents": "Short-term effects of prednisolone on neuromuscular transmission in normal rats and those with experimental autoimmune myasthenia gravis. Electrophysiological investigations of the effects of bath-applied prednisolone at the neuromuscular junction were performed in muscles from normal rats and rats with experimental autoimmune myasthenia gravis (EAMG). In muscles from both groups, prednisolone reversible and significantly depressed the amplitudes of minature end-plate potentials (MEPPs), end-plate potentials (EPPs) and indirectly elicited action potentials (APs) without affecting resting membrane potentials. Prednisolone also caused a significant reduction in EPP rise time to peak and half-decay time while markedly increasing MEPP frequency and AP rise time to peak and duration. These effects were shown to be dose-dependent. The percentage decrease in amplitude after prednisolone perfusion was similar for EPPs and MEPPs, indicating that the depressive effect of prednisolone at the junction is postsynaptic. In all of the parameters studied, the percentage effect of prednisolone was the same in EAMG and normal preparations. No stimulus-linked repetitive EPPs or APs were observed after prednisolone. It is concluded that prednisolone has a depressive effect on neuromuscular transmission, but that this occurs only at high concentrations of the drug which are not achieved during the treatment of myasthenia gravis."}
{"id": "PMID:220392", "title": "Monovalent cation transport in myotonic dystrophy. Na-K pump ratio in erythrocytes.", "content": "Myotonic dystrophy is a dominantly-inherited disorder which affects skeletal muscle in combination with several other systems. Because of abnormalities in red blood cells, a universal membrane defect has been proposed as the primary disturbance. Erythrocyte cation pump ratios have also been reported to be abnormal. Hyperinsulinemia and glucose intolerance are present in a large number of patients. Since dramatic effects of insulin on membrane cation transport have been shown in several tissues, notably skeletal muscle, we wished first to confirm reports of altered pump ratio in these patients and then to evaluate the effects of insulin on cation fluxes. However, in our experiments myotonic dystrophy patients had normal pump ratios when compared with disease controls.", "contents": "Monovalent cation transport in myotonic dystrophy. Na-K pump ratio in erythrocytes. Myotonic dystrophy is a dominantly-inherited disorder which affects skeletal muscle in combination with several other systems. Because of abnormalities in red blood cells, a universal membrane defect has been proposed as the primary disturbance. Erythrocyte cation pump ratios have also been reported to be abnormal. Hyperinsulinemia and glucose intolerance are present in a large number of patients. Since dramatic effects of insulin on membrane cation transport have been shown in several tissues, notably skeletal muscle, we wished first to confirm reports of altered pump ratio in these patients and then to evaluate the effects of insulin on cation fluxes. However, in our experiments myotonic dystrophy patients had normal pump ratios when compared with disease controls."}
{"id": "PMID:220393", "title": "Transketolase inhibition and uremic peripheral sensory neuropathy.", "content": "The relationships between predialysis and postdialysis erythrocyte transketolase activities and symptoms of uremic peripheral neuropathy were studied prospectively for 21 months in 19 chronic hemodialysis patients. In all patients the predialysis activity was observed to be sometimes greater and sometimes less than the postdialysis activity. These observations were interpreted as indicating the coexistence in uremic blood of stimulatory and inhibitory substances which influence the enzyme independently. After enzyme stimulation was assumed to be a constant feature of uremia, the expected stimulated activity in erythrocytes of predialysis blood was found to be variably inhibited up to about 55% in these patients. The occurrence of paresthesiae was closely correlated with prolonged erythrocytes transketolase inhibition which in most cases reached a level of about 40%. Our conclusion is that the magnitude of erythroycte transketolase inhibition above a certain minimum level, together with its duration, is associated with symptoms of sensory peripheral neuropathy in the uremic patient. It is therefore predicted that such measurements may be usefully applied in ascertaining the extent of hemodialysis needed to prevent the development of this pathological state.", "contents": "Transketolase inhibition and uremic peripheral sensory neuropathy. The relationships between predialysis and postdialysis erythrocyte transketolase activities and symptoms of uremic peripheral neuropathy were studied prospectively for 21 months in 19 chronic hemodialysis patients. In all patients the predialysis activity was observed to be sometimes greater and sometimes less than the postdialysis activity. These observations were interpreted as indicating the coexistence in uremic blood of stimulatory and inhibitory substances which influence the enzyme independently. After enzyme stimulation was assumed to be a constant feature of uremia, the expected stimulated activity in erythrocytes of predialysis blood was found to be variably inhibited up to about 55% in these patients. The occurrence of paresthesiae was closely correlated with prolonged erythrocytes transketolase inhibition which in most cases reached a level of about 40%. Our conclusion is that the magnitude of erythroycte transketolase inhibition above a certain minimum level, together with its duration, is associated with symptoms of sensory peripheral neuropathy in the uremic patient. It is therefore predicted that such measurements may be usefully applied in ascertaining the extent of hemodialysis needed to prevent the development of this pathological state."}
{"id": "PMID:220394", "title": "Pathogenesis of visna. IV. Spinal fluid studies.", "content": "Visna is a persistent retrovirus infection of sheep which produces a chronic progressive paralytic disease after an incubation period lasting from months to years. The cerebrospinal fluid (CSF) was repeatedly sampled in a group of Icelandic sheep which were infected intracerebrally and followed up to 42 months. Minimal levels of infectious virus were isolated from the cerebrospinal fluid (CSF) up to 4 months after infection after which CSF neutralizing antibodies appeared in many sheep. These antibodies varied in titer and in some animals exceeded serum antibody levels which were moderate to high. CSF antibody is apparently produced within the CNS by local proliferation of B cell clones, and is accompanied by the appearance of considerable numbers of plasma cells in the neural parenchyma. Some sheep raised serum antibody to a second serotype of visna virus and in a number of these animals heterotypic antibody was also found in the CSF. An increase in CSF leukocytes often occurs within 1 to 3 months following infection and may then persist or wane. A persistent high level of CSF cells is an indicator of progressive CNS disease and such animals are more likely to yield virus, have higher CSF antibody levels, more severe CNS lesions, and an enhanced risk of clinical illness (progressive paralysis). CSF cells are predominantly macrophages and lymphocytes, with a consistent minority of plasma cells.", "contents": "Pathogenesis of visna. IV. Spinal fluid studies. Visna is a persistent retrovirus infection of sheep which produces a chronic progressive paralytic disease after an incubation period lasting from months to years. The cerebrospinal fluid (CSF) was repeatedly sampled in a group of Icelandic sheep which were infected intracerebrally and followed up to 42 months. Minimal levels of infectious virus were isolated from the cerebrospinal fluid (CSF) up to 4 months after infection after which CSF neutralizing antibodies appeared in many sheep. These antibodies varied in titer and in some animals exceeded serum antibody levels which were moderate to high. CSF antibody is apparently produced within the CNS by local proliferation of B cell clones, and is accompanied by the appearance of considerable numbers of plasma cells in the neural parenchyma. Some sheep raised serum antibody to a second serotype of visna virus and in a number of these animals heterotypic antibody was also found in the CSF. An increase in CSF leukocytes often occurs within 1 to 3 months following infection and may then persist or wane. A persistent high level of CSF cells is an indicator of progressive CNS disease and such animals are more likely to yield virus, have higher CSF antibody levels, more severe CNS lesions, and an enhanced risk of clinical illness (progressive paralysis). CSF cells are predominantly macrophages and lymphocytes, with a consistent minority of plasma cells."}
{"id": "PMID:220395", "title": "Derangement of neuronal migration in a child with multiple congenital anomalies, two congenital neoplasms, without apparent chromosomal abnormalities.", "content": "A live-born male infant with multiple severe abnormalities, two congenital neoplasms, a neuroblastoma and nephroblastoma, and without apparent chromosomal abnormalities, is described. The neuropathologic findings were a holoprosencephalic type defect with disturbance of neuronal migration to the cortical plate. Comparison of the overall findings with cases presenting similar multiple congenital abnormalities indicates that this case either demonstrates previously unrecognized features of these syndromes, or is unique.", "contents": "Derangement of neuronal migration in a child with multiple congenital anomalies, two congenital neoplasms, without apparent chromosomal abnormalities. A live-born male infant with multiple severe abnormalities, two congenital neoplasms, a neuroblastoma and nephroblastoma, and without apparent chromosomal abnormalities, is described. The neuropathologic findings were a holoprosencephalic type defect with disturbance of neuronal migration to the cortical plate. Comparison of the overall findings with cases presenting similar multiple congenital abnormalities indicates that this case either demonstrates previously unrecognized features of these syndromes, or is unique."}
{"id": "PMID:220397", "title": "Effects of vitamin E deficiency on the activities of lipid-requiring enzymes in rabbit liver and muscle.", "content": "The effects of vitamin E deficiency on membrane integrity were studied by examining the temperature dependence of membrane-bound enzyme activities in liver mitochondria and microsome and in muscle sarcoplasmic reticulum. In vitamin E-deficient rabbits, the specific activities at 37 degrees of mitochondrial oligomycin-sensitive ATPase (EC 3.6.1.3), beta-hydroxybutyrate dehydrogenase (EC 1.1.1.30), and microsomal glucose-6-phosphatase (EC 3.1.3.9) were increased, whereas those of microsomal NADH cytochrome C reductase (EC 1.6.99.3) and sarcoplasmic reticulum Ca-ATPase were reduced in comparison to control rabbits. Arrhenius plots of activity against temperature yielded a linear plot over the range 10 to 40 degrees in the case of beta-hydroxybutyrate dehydrogenase, NADH cytochrome C reductase and Ca-ATPase, and multiple discontinuities for glucose-6-phosphatase and oligomycin-sensitive ATPase. In control rabbits, all five enzymes showed a single discontinuity in the Arrhenius plot over the range 16 to 19 degrees. These results reflect changes in the microenvironment of membrane-bound enzymes as a consequence of vitamin E depletion.", "contents": "Effects of vitamin E deficiency on the activities of lipid-requiring enzymes in rabbit liver and muscle. The effects of vitamin E deficiency on membrane integrity were studied by examining the temperature dependence of membrane-bound enzyme activities in liver mitochondria and microsome and in muscle sarcoplasmic reticulum. In vitamin E-deficient rabbits, the specific activities at 37 degrees of mitochondrial oligomycin-sensitive ATPase (EC 3.6.1.3), beta-hydroxybutyrate dehydrogenase (EC 1.1.1.30), and microsomal glucose-6-phosphatase (EC 3.1.3.9) were increased, whereas those of microsomal NADH cytochrome C reductase (EC 1.6.99.3) and sarcoplasmic reticulum Ca-ATPase were reduced in comparison to control rabbits. Arrhenius plots of activity against temperature yielded a linear plot over the range 10 to 40 degrees in the case of beta-hydroxybutyrate dehydrogenase, NADH cytochrome C reductase and Ca-ATPase, and multiple discontinuities for glucose-6-phosphatase and oligomycin-sensitive ATPase. In control rabbits, all five enzymes showed a single discontinuity in the Arrhenius plot over the range 16 to 19 degrees. These results reflect changes in the microenvironment of membrane-bound enzymes as a consequence of vitamin E depletion."}
{"id": "PMID:220398", "title": "A classification of dysplastic forms of dentin.", "content": "Considerable effort has been made in the past to describe the morphologic changes in dentin which characterize various developmental disturbances of teeth. However, there appears to be no previous attempt to describe the spectrum of changes which may be exhibited by abnormal dentin. This paper presents a classification of dysplastic forms of dentin with definitions and illustrations of each abnormality. The classification was derived from reviewing the literature and from a study of 82 odontomas, examples of specific developmental disorders of dentin, regional odontodysplasia, and systemic conditions affecting dentin.", "contents": "A classification of dysplastic forms of dentin. Considerable effort has been made in the past to describe the morphologic changes in dentin which characterize various developmental disturbances of teeth. However, there appears to be no previous attempt to describe the spectrum of changes which may be exhibited by abnormal dentin. This paper presents a classification of dysplastic forms of dentin with definitions and illustrations of each abnormality. The classification was derived from reviewing the literature and from a study of 82 odontomas, examples of specific developmental disorders of dentin, regional odontodysplasia, and systemic conditions affecting dentin."}
{"id": "PMID:220399", "title": "Granular cell tumors of the head and neck.", "content": "Forth-two granular cell tumors of the head and neck were collected and studied with light and electron microscopy. Granular cells were found in four odontogenic tumors, two congenital epulides of newborn infants, and 36 myoblastoma lesions of the skin and mucous membranes. Support is presented for the hypothesis that granular cells represent an unusual nonspecific degenerative process and that nonodontogenic granular cell tumors develop from undifferentiated mesenchymal cells that subsequently undergo autophagocytosis.", "contents": "Granular cell tumors of the head and neck. Forth-two granular cell tumors of the head and neck were collected and studied with light and electron microscopy. Granular cells were found in four odontogenic tumors, two congenital epulides of newborn infants, and 36 myoblastoma lesions of the skin and mucous membranes. Support is presented for the hypothesis that granular cells represent an unusual nonspecific degenerative process and that nonodontogenic granular cell tumors develop from undifferentiated mesenchymal cells that subsequently undergo autophagocytosis."}
{"id": "PMID:220400", "title": "Analysis of postsurgical neurologic alteration in the trigeminal nerve.", "content": "Neurologic alteration in 36 patients who had received either a sagittal split osteotomy, an intraoral vertical ramus osteotomy, or a mandibular vestibuloplasty was evaluated by questionnaire, detailed neurosensory examination, and personality testing. Subjective sensory alteration was reported by 69.4% of the entire group; neurosensory examination showed demonstrable neuropathy in 54% of the 72 nerve divisions that were examined, with the greatest incidence, 84.6%, in the group that had received sagittal split osteotomies. Personality testing indicated that dysesthetic patients experienced greater degrees of neuroticism and depression than did patients without pain.", "contents": "Analysis of postsurgical neurologic alteration in the trigeminal nerve. Neurologic alteration in 36 patients who had received either a sagittal split osteotomy, an intraoral vertical ramus osteotomy, or a mandibular vestibuloplasty was evaluated by questionnaire, detailed neurosensory examination, and personality testing. Subjective sensory alteration was reported by 69.4% of the entire group; neurosensory examination showed demonstrable neuropathy in 54% of the 72 nerve divisions that were examined, with the greatest incidence, 84.6%, in the group that had received sagittal split osteotomies. Personality testing indicated that dysesthetic patients experienced greater degrees of neuroticism and depression than did patients without pain."}
{"id": "PMID:220405", "title": "Adrenergic and serotonergic receptor binding in rat brain after chronic desmethylimipramine treatment.", "content": "The effects of chronic administration of the tricyclic antidepressant agent desmethylimipramine (DMI) on brain adrenergic and serotonergic receptor binding processes were studied. We examined the kinetic properties of alpha adrenergic, beta adrenergic and serotonergic receptor binding sites in cortical and subcortical brain regions of rats treated chronically for various time periods with DMI(6 mg/kg i.p. daily). After 1 week of daily injections, beta receptor binding density in the cortex was significantly decreased. The reduced density of the cortical beta receptors was evident throughout a 12-week administration period. It was not until after 6 weeks of DMI administration that a significant reduction in the subcortical beta receptors was evident. Compared to saline-injected controls, chronic DMI administration  lowered [3H]dihydroalprenolol binding in the hippocampus but not in the striatum. After 12 weeks of DMI we detected no differences in alpha adrenergic binding characteristics in the cortex or subcortical forebrain using [3H]dihydroergocryptine as the binding ligand. There was no consistent alteration in the cortical serotonin receptor densities throughout the 12 weeks of DMI administration, and DMI had no effect on the serotonergic binding characteristics in the subcortical forebrain region. We conclude that chronic DMI administration selectively decreases the density of beta adrenergic receptors in rat brain.", "contents": "Adrenergic and serotonergic receptor binding in rat brain after chronic desmethylimipramine treatment. The effects of chronic administration of the tricyclic antidepressant agent desmethylimipramine (DMI) on brain adrenergic and serotonergic receptor binding processes were studied. We examined the kinetic properties of alpha adrenergic, beta adrenergic and serotonergic receptor binding sites in cortical and subcortical brain regions of rats treated chronically for various time periods with DMI(6 mg/kg i.p. daily). After 1 week of daily injections, beta receptor binding density in the cortex was significantly decreased. The reduced density of the cortical beta receptors was evident throughout a 12-week administration period. It was not until after 6 weeks of DMI administration that a significant reduction in the subcortical beta receptors was evident. Compared to saline-injected controls, chronic DMI administration  lowered [3H]dihydroalprenolol binding in the hippocampus but not in the striatum. After 12 weeks of DMI we detected no differences in alpha adrenergic binding characteristics in the cortex or subcortical forebrain using [3H]dihydroergocryptine as the binding ligand. There was no consistent alteration in the cortical serotonin receptor densities throughout the 12 weeks of DMI administration, and DMI had no effect on the serotonergic binding characteristics in the subcortical forebrain region. We conclude that chronic DMI administration selectively decreases the density of beta adrenergic receptors in rat brain."}
{"id": "PMID:220407", "title": "Naloxone and naltrexone: actions and interactions at an opiate drug receptor on frog skeletal muscle fibers.", "content": "Extracellular and intracellular microelectrode studies were conducted to test the actions and interactions of naloxone and naltrexone, two supposedly \"pure\" opiate antagonists. Both were shown to depress excitability and action potential production when applied in relatively high concentrations. Low naltrexone concentrations antagonized the depression produced by naloxone, but low naloxone concentrations did not antagonize the depression produced by high naltrexone concentrations. Naltrexone also depressed the stimulus-induced increase in potassium conductance (gK) which naloxone did not do. Thus, the naloxone depression is mediated via an opiate drug receptor, whereas naltrexone in high concentrations produces a \"local anesthetic-like\" depression not involving the opiate drug receptor.", "contents": "Naloxone and naltrexone: actions and interactions at an opiate drug receptor on frog skeletal muscle fibers. Extracellular and intracellular microelectrode studies were conducted to test the actions and interactions of naloxone and naltrexone, two supposedly \"pure\" opiate antagonists. Both were shown to depress excitability and action potential production when applied in relatively high concentrations. Low naltrexone concentrations antagonized the depression produced by naloxone, but low naloxone concentrations did not antagonize the depression produced by high naltrexone concentrations. Naltrexone also depressed the stimulus-induced increase in potassium conductance (gK) which naloxone did not do. Thus, the naloxone depression is mediated via an opiate drug receptor, whereas naltrexone in high concentrations produces a \"local anesthetic-like\" depression not involving the opiate drug receptor."}
{"id": "PMID:220403", "title": "Pan uveitis and retinitis in neonatal herpes simplex infection.", "content": "Neonatal infection with herpes simplex virus is, in recent years, a more frequently recognized complication of maternal genital herpes infection. Chorioretinitis has been described in approximately 16 cases. A case report is presented in which clinical photographs of the intraocular lesions are presented.", "contents": "Pan uveitis and retinitis in neonatal herpes simplex infection. Neonatal infection with herpes simplex virus is, in recent years, a more frequently recognized complication of maternal genital herpes infection. Chorioretinitis has been described in approximately 16 cases. A case report is presented in which clinical photographs of the intraocular lesions are presented."}
{"id": "PMID:220402", "title": "Aicardi's syndrome: a report of four cases and review of the literature.", "content": "Four patients with Aicardi's syndrome (infantile flexion spasms, agenesis of the corpus callosum, and ocular anomalies) are reported, along with photographs of their characteristic fundus abnormalities. The etiology of the syndrome is unclear, but its occurrence exclusively in female patients suggests the possibility of a genetic factor. The ocular abnormalities of Aicardi's Syndrome are distinguishable from, but may be confused with, those of congenital toxoplasmosis and cytomegalic inclusion disease. The syndrome can be identified clinically with a high degree of certainty. Ophthalmologists who are familiar with the syndrome may be helpful in the differential diagnosis.", "contents": "Aicardi's syndrome: a report of four cases and review of the literature. Four patients with Aicardi's syndrome (infantile flexion spasms, agenesis of the corpus callosum, and ocular anomalies) are reported, along with photographs of their characteristic fundus abnormalities. The etiology of the syndrome is unclear, but its occurrence exclusively in female patients suggests the possibility of a genetic factor. The ocular abnormalities of Aicardi's Syndrome are distinguishable from, but may be confused with, those of congenital toxoplasmosis and cytomegalic inclusion disease. The syndrome can be identified clinically with a high degree of certainty. Ophthalmologists who are familiar with the syndrome may be helpful in the differential diagnosis."}
{"id": "PMID:220410", "title": "Changes in total and quantal release of acetylcholine in the mouse diaphragm during activation and inhibition of membrane ATPase.", "content": "1. Acetylcholine (ACh) released from mouse diaphragm was gel filtrated and estimated by bio-assay and compared with electrophysiologically measured quantal release, expressed either as frequency of miniature end-plate potentials or quantum content of end-plate potentials. 2. Activation of Na+-K+-dependent membrane ATPase (membrane ATPase) in Na+-loaded muscles lowered the total amount of ACh released at rest to one tenth of the control value, but quantal release remained unchanged. 3. Inhibition of membrane ATPase by 2 X 10(-5) M-ouabain or by K-free solution led to an increase in total release and to a delayed progressive increase in quantal release. When Ca2+ was removed only the total release was enhanced. 4. Depolarization of the diaphragm by 8, 11 and 14 mM-K increased both total and quantal release only in the presence of Ca2+ in the perfusion medium. When Ca2+ was removed, no significant increase in release was observed. 5. The total and quantal release in response to 2 Hz stimulation of the preparation was increased 1.4 and 45 times, respectively. It is concluded that the total amount of ACh released at rest consists of two fractions, quantal and non-quantal, the former representing about 1% of the total release.", "contents": "Changes in total and quantal release of acetylcholine in the mouse diaphragm during activation and inhibition of membrane ATPase. 1. Acetylcholine (ACh) released from mouse diaphragm was gel filtrated and estimated by bio-assay and compared with electrophysiologically measured quantal release, expressed either as frequency of miniature end-plate potentials or quantum content of end-plate potentials. 2. Activation of Na+-K+-dependent membrane ATPase (membrane ATPase) in Na+-loaded muscles lowered the total amount of ACh released at rest to one tenth of the control value, but quantal release remained unchanged. 3. Inhibition of membrane ATPase by 2 X 10(-5) M-ouabain or by K-free solution led to an increase in total release and to a delayed progressive increase in quantal release. When Ca2+ was removed only the total release was enhanced. 4. Depolarization of the diaphragm by 8, 11 and 14 mM-K increased both total and quantal release only in the presence of Ca2+ in the perfusion medium. When Ca2+ was removed, no significant increase in release was observed. 5. The total and quantal release in response to 2 Hz stimulation of the preparation was increased 1.4 and 45 times, respectively. It is concluded that the total amount of ACh released at rest consists of two fractions, quantal and non-quantal, the former representing about 1% of the total release."}
{"id": "PMID:220411", "title": "Direct inhibition of gastric secretion and mucosal blood flow by arachidonic acid.", "content": "1. Gastric acid and pepsin secretion stimulated almost maximally by i.v. infusion of histamine, the mucosal blood flow, and the immunoreactive prostaglandin E (PGE) content have been measured following arachidonic acid administration either intra-arterially or topically to the mucosa of the fundic portion of a stomach kept in a Lucite chamber. 2. Arachidonic acid administered directly to the stomach produced a marked and significant inhibition of histamine-induced gastric secretion accompanied by a reduction in mucosal microcirculation and a rise in the immunoreactive PGE content in the gastric juice. 3. These secretory and circulatory changes induced by arachidonic acid were prevented by pretreatment of the gastic mucosa with indomethacin, a potent inhibitor of the prostaglandin synthetase system. 4. Arachidonic acid infused intra-arterially in graded doses resulted in a dose-dependent reduction in gastric acid secretion, mucosal blood flow and cyclic AMP mucosal content. 5. These studies indicate that arachidonic acid applied directly to the stomach causes a marked gastric secretory inhibition, probably due at least in part to the enzymic transformation of arachidonic acid to prostaglandins and possibly other active lipids responsible for the changes in the gastric mucosal microcirculation and cyclic AMP mucosal content.", "contents": "Direct inhibition of gastric secretion and mucosal blood flow by arachidonic acid. 1. Gastric acid and pepsin secretion stimulated almost maximally by i.v. infusion of histamine, the mucosal blood flow, and the immunoreactive prostaglandin E (PGE) content have been measured following arachidonic acid administration either intra-arterially or topically to the mucosa of the fundic portion of a stomach kept in a Lucite chamber. 2. Arachidonic acid administered directly to the stomach produced a marked and significant inhibition of histamine-induced gastric secretion accompanied by a reduction in mucosal microcirculation and a rise in the immunoreactive PGE content in the gastric juice. 3. These secretory and circulatory changes induced by arachidonic acid were prevented by pretreatment of the gastic mucosa with indomethacin, a potent inhibitor of the prostaglandin synthetase system. 4. Arachidonic acid infused intra-arterially in graded doses resulted in a dose-dependent reduction in gastric acid secretion, mucosal blood flow and cyclic AMP mucosal content. 5. These studies indicate that arachidonic acid applied directly to the stomach causes a marked gastric secretory inhibition, probably due at least in part to the enzymic transformation of arachidonic acid to prostaglandins and possibly other active lipids responsible for the changes in the gastric mucosal microcirculation and cyclic AMP mucosal content."}
{"id": "PMID:220412", "title": "Normal distribution and denervation changes of neurotransmitter related enzymes in cholinergic neurones.", "content": "1. The activities of choline acetyltransferase (CAT) and acetylcholinesterase (AChE) were assayed in adult pigeon ciliary ganglia, in the post-synaptic ciliary and choroid nerves, and in ciliary nerve iris terminals isolated from control birds and from animals from which the oculomotor nerve was previously transected. Enzyme activity levels were also measured in the iris terminals after surgical section of the ciliary nerves. From differences in enzyme activity between control and 3-day denervated tissues, the localization of CAT and AChE in pre- and post-synaptic elements of the ganglia and at the iris neuromuscular junctions was estimated. The fate of the preganglionic nerve terminals after denervation was investigated by electron microscopic examination of ganglia after surgical section of the oculomotor nerve.2. The CAT activity in the ganglion was distributed as follows: 60% in presynaptic elements, 31% in cell somas, and 9% in intraganglionic post-synaptic axons; in the iris junctions, 98% of the activity was present in the ciliary nerve terminals. For AChE: 20% was present in the preganglionic terminals, 69% in ganglion cell somas and the remaining 11% in post-ganglionic axons; at the neuromuscular iris junctions, 20% was found in the ciliary nerve terminals and 80% in the iris striated muscle.3. The first changes in the fine structure of the nerve terminals were observed 14 hr after surgery, and by 24 hr marked alteration of the synaptic structure were clearly recognized. No preganglionic endings were found in 3 day-old denervated ganglia.4. There was a positive correlation between CAT activity in the control iris nerve terminals and in ganglia. After denervation, when the activity of the enzyme decreased in ganglion cell somas, there was a corresponding decrease in the post-synaptic nerves. These two findings suggest that CAT slow axoplasmic transport is related to its perikarial concentration.5. There was a 60% reduction of CAT activity in the post-synaptic elements, assayed in the 10-day denervated ganglia, which was accompanied by a 30% decrease in activity in the iris nerve terminals. Similarly, post-synaptic AChE decreased approximately 30% in the ganglion and approximately 30% in the iris 10 days after section of the oculomotor nerve. At the same time, CAT activity also decreased in the nerve trunks, 70% at the ciliary nerve and 40% at the choroid; for AChE there were smaller changes.6. In contrast to CAT and AChE, there were no differences in ganglionic protein content, or lactate dehydrogenase (LDH), co-enzyme A (CoA) and monoamine oxidase (MAO) levels between short-term (3 days) and long-term (10 days) denervated ganglia.7. The later decrease of CAT and AChE activity in the cell somas, axons and nerve terminals after long-term preganglionic transection suggests that the activity of these enzymes is regulated across the synapses. It is postulated that the AChE regulation is part of a general ;trophic interaction' between neurones, but that the trans-synaptic modulation of CAT is specific for cholinergic cells.", "contents": "Normal distribution and denervation changes of neurotransmitter related enzymes in cholinergic neurones. 1. The activities of choline acetyltransferase (CAT) and acetylcholinesterase (AChE) were assayed in adult pigeon ciliary ganglia, in the post-synaptic ciliary and choroid nerves, and in ciliary nerve iris terminals isolated from control birds and from animals from which the oculomotor nerve was previously transected. Enzyme activity levels were also measured in the iris terminals after surgical section of the ciliary nerves. From differences in enzyme activity between control and 3-day denervated tissues, the localization of CAT and AChE in pre- and post-synaptic elements of the ganglia and at the iris neuromuscular junctions was estimated. The fate of the preganglionic nerve terminals after denervation was investigated by electron microscopic examination of ganglia after surgical section of the oculomotor nerve.2. The CAT activity in the ganglion was distributed as follows: 60% in presynaptic elements, 31% in cell somas, and 9% in intraganglionic post-synaptic axons; in the iris junctions, 98% of the activity was present in the ciliary nerve terminals. For AChE: 20% was present in the preganglionic terminals, 69% in ganglion cell somas and the remaining 11% in post-ganglionic axons; at the neuromuscular iris junctions, 20% was found in the ciliary nerve terminals and 80% in the iris striated muscle.3. The first changes in the fine structure of the nerve terminals were observed 14 hr after surgery, and by 24 hr marked alteration of the synaptic structure were clearly recognized. No preganglionic endings were found in 3 day-old denervated ganglia.4. There was a positive correlation between CAT activity in the control iris nerve terminals and in ganglia. After denervation, when the activity of the enzyme decreased in ganglion cell somas, there was a corresponding decrease in the post-synaptic nerves. These two findings suggest that CAT slow axoplasmic transport is related to its perikarial concentration.5. There was a 60% reduction of CAT activity in the post-synaptic elements, assayed in the 10-day denervated ganglia, which was accompanied by a 30% decrease in activity in the iris nerve terminals. Similarly, post-synaptic AChE decreased approximately 30% in the ganglion and approximately 30% in the iris 10 days after section of the oculomotor nerve. At the same time, CAT activity also decreased in the nerve trunks, 70% at the ciliary nerve and 40% at the choroid; for AChE there were smaller changes.6. In contrast to CAT and AChE, there were no differences in ganglionic protein content, or lactate dehydrogenase (LDH), co-enzyme A (CoA) and monoamine oxidase (MAO) levels between short-term (3 days) and long-term (10 days) denervated ganglia.7. The later decrease of CAT and AChE activity in the cell somas, axons and nerve terminals after long-term preganglionic transection suggests that the activity of these enzymes is regulated across the synapses. It is postulated that the AChE regulation is part of a general ;trophic interaction' between neurones, but that the trans-synaptic modulation of CAT is specific for cholinergic cells."}
{"id": "PMID:220413", "title": "The influence of corticosteroids on the secretion of corticotrophin and its hypothalamic releasing hormone.", "content": "1. The effects of stress, adrenalectomy and corticosterone treatment on the functional activity of the hypothalamo-pituitary-adrenocortical system have been studied using highly sensitive and precise bio-assay methods for the determination of ACTH and CRH.2. Adrenalectomy resulted in a rise and corticosterone treatment a fall in the hypothalamic CRH content and the plasma ACTH concentration.3. Stress caused a fall followed by a rise in the hypothalamic CRH content, a rise in the pituitary and plasma ACTH concentrations and an increase in the plasma corticosterone concentration.4. The stress-induced changes in hypothalamic CRH content and pituitary and plasma ACTH were exaggerated in adrenalectomized rats but normal in adrenalectomized rats treated with corticosterone. They were also normal in animals injected I.P. with corticosterone 15 min before the stress but inhibited in those similarly treated 60 min previously.5. The ability of adenohypophyses and hypothalami to synthesize and release in vitro ACTH and CRH respectively in response to trophic stimuli was exaggerated in glands removed from adrenalectomized rats and reduced in those removed from corticosterone-treated rats.6. Addition of corticosterone to the pre-incubation medium reduced the capacities of adenohypophyses and hypothalami removed from untreated rats to synthesize and release ACTH and CRH respectively.", "contents": "The influence of corticosteroids on the secretion of corticotrophin and its hypothalamic releasing hormone. 1. The effects of stress, adrenalectomy and corticosterone treatment on the functional activity of the hypothalamo-pituitary-adrenocortical system have been studied using highly sensitive and precise bio-assay methods for the determination of ACTH and CRH.2. Adrenalectomy resulted in a rise and corticosterone treatment a fall in the hypothalamic CRH content and the plasma ACTH concentration.3. Stress caused a fall followed by a rise in the hypothalamic CRH content, a rise in the pituitary and plasma ACTH concentrations and an increase in the plasma corticosterone concentration.4. The stress-induced changes in hypothalamic CRH content and pituitary and plasma ACTH were exaggerated in adrenalectomized rats but normal in adrenalectomized rats treated with corticosterone. They were also normal in animals injected I.P. with corticosterone 15 min before the stress but inhibited in those similarly treated 60 min previously.5. The ability of adenohypophyses and hypothalami to synthesize and release in vitro ACTH and CRH respectively in response to trophic stimuli was exaggerated in glands removed from adrenalectomized rats and reduced in those removed from corticosterone-treated rats.6. Addition of corticosterone to the pre-incubation medium reduced the capacities of adenohypophyses and hypothalami removed from untreated rats to synthesize and release ACTH and CRH respectively."}
{"id": "PMID:220414", "title": "The effect of nutritional state on neuromuscular transmission in the rat.", "content": "1. Evoked end-plate potentials (e.p.p.s) were recorded in phrenic nerve-hemidiaphragm preparations from rats which had been subjected to periods of dietary restriction. 2. The mean quantum content of the first e.p.p. of trains of e.p.p.s was significantly increased after 1 week of dietary restriction in 30-day-old but not in 110-day-old rats. 3. The mean quantum content of plateau e.p.p.s elicited at a frequency of 10 Hz was not significantly affected by brief periods of dietary restriction in either 30-day-old or 110-day-old rats. 4. In the younger animals there was found to be a decrease in the safety factor of neuromuscular transmission following dietary restriction when this parameter was calculated using previously reported values for the amplitude of spontaneous miniature end-plate potentials (m.e.p.p.s) after such a restricted diet. 5. Such rapid changes in neuromuscular transmission following brief periods of dietary restriction indicate that great care is required in the choice of adequate control animals when food intake is altered by experimental procedures.", "contents": "The effect of nutritional state on neuromuscular transmission in the rat. 1. Evoked end-plate potentials (e.p.p.s) were recorded in phrenic nerve-hemidiaphragm preparations from rats which had been subjected to periods of dietary restriction. 2. The mean quantum content of the first e.p.p. of trains of e.p.p.s was significantly increased after 1 week of dietary restriction in 30-day-old but not in 110-day-old rats. 3. The mean quantum content of plateau e.p.p.s elicited at a frequency of 10 Hz was not significantly affected by brief periods of dietary restriction in either 30-day-old or 110-day-old rats. 4. In the younger animals there was found to be a decrease in the safety factor of neuromuscular transmission following dietary restriction when this parameter was calculated using previously reported values for the amplitude of spontaneous miniature end-plate potentials (m.e.p.p.s) after such a restricted diet. 5. Such rapid changes in neuromuscular transmission following brief periods of dietary restriction indicate that great care is required in the choice of adequate control animals when food intake is altered by experimental procedures."}
{"id": "PMID:220415", "title": "Signal transmission from red cones to horizontal cells in the turtle retina.", "content": "1. Intracellular recordings were made from L-type horizontal cells in the retina of the turtle Pseudemys scripta elegans. The responses were evoked by 500 msec pulses of 'white' light. 2. L-type horizontal cells were classified as either, 'small receptive field' s.r.f. or 'large receptive field' l.r.f. based upon (1) receptive field size and (2) kinetics of responses to test flashes covering small and big spots. 3. Constant illumination of the entire receptive field, with any intensity studied, evoked a response that reached a peak and then slowly sagged back to a steady-state level that was about half the peak response. 4. Termination of backgrounds resulted in a very fast recovery of the membrane potential that overshot the dark-adapted potential. This 'off' response had faster kinetics in horizontal cells than in red cones. 5. The intensity-response curve measured around any background intensity was shifted along the log intensity axis toward higher test intensities. The curves obtained under light-adapted conditions were sharper than the curve measured in the dark-adapted state. 6. The photoresponses of red cones and s.r.f. horizontal cells were compared under similar states of adaptation. In the dark-adapted state of the gain, expressed as the millivolt change in the horizontal cell per millivolt change in the cone, was not linearly related to cone potential, and was highest for dim stimuli. Light-adaption modified the synaptic transmission to make the horizontal cells most sensitive to light modulation around the background illumination. 7. The mechanisms by which signal transmission can be modified by light-adaptation are discussed in terms of transmitter release by the presynaptic terminals and its binding to post-synaptic sites.", "contents": "Signal transmission from red cones to horizontal cells in the turtle retina. 1. Intracellular recordings were made from L-type horizontal cells in the retina of the turtle Pseudemys scripta elegans. The responses were evoked by 500 msec pulses of 'white' light. 2. L-type horizontal cells were classified as either, 'small receptive field' s.r.f. or 'large receptive field' l.r.f. based upon (1) receptive field size and (2) kinetics of responses to test flashes covering small and big spots. 3. Constant illumination of the entire receptive field, with any intensity studied, evoked a response that reached a peak and then slowly sagged back to a steady-state level that was about half the peak response. 4. Termination of backgrounds resulted in a very fast recovery of the membrane potential that overshot the dark-adapted potential. This 'off' response had faster kinetics in horizontal cells than in red cones. 5. The intensity-response curve measured around any background intensity was shifted along the log intensity axis toward higher test intensities. The curves obtained under light-adapted conditions were sharper than the curve measured in the dark-adapted state. 6. The photoresponses of red cones and s.r.f. horizontal cells were compared under similar states of adaptation. In the dark-adapted state of the gain, expressed as the millivolt change in the horizontal cell per millivolt change in the cone, was not linearly related to cone potential, and was highest for dim stimuli. Light-adaption modified the synaptic transmission to make the horizontal cells most sensitive to light modulation around the background illumination. 7. The mechanisms by which signal transmission can be modified by light-adaptation are discussed in terms of transmitter release by the presynaptic terminals and its binding to post-synaptic sites."}
{"id": "PMID:220416", "title": "The effect of theophylline and dibutyryl cyclic AMP on the uptake of radioactive calcium and phosphate ions by boar and human spermatozoa.", "content": "Radioactive calcium uptake by suspensions of washed boar and human spermatozoa was inhibited by the mitochondrial uncoupling agent carbonylcyanide-p-trifluoromethoxy-phenylhydrazone (FCCP). Theophylline + dibutyryl cyclic AMP also inhibited calcium uptake in the presence or absence of FCCP. Uptake of low concentrations of calcium (0 . 1 mM) was inhibited by the calcium ionophore A23187, but at high calcium concentrations the ionophore stimulated calcium uptake. These observations are explained in terms of a mechanism for the regulation of calcium uptake in spermatozoa based on competing mitochondrial and plasma membrane pumps. Uptake of 32P was also inhibited. These effects provide evidence that cyclic AMP plays a role in the transport of ions across the plasma membrane of spermatozoa.", "contents": "The effect of theophylline and dibutyryl cyclic AMP on the uptake of radioactive calcium and phosphate ions by boar and human spermatozoa. Radioactive calcium uptake by suspensions of washed boar and human spermatozoa was inhibited by the mitochondrial uncoupling agent carbonylcyanide-p-trifluoromethoxy-phenylhydrazone (FCCP). Theophylline + dibutyryl cyclic AMP also inhibited calcium uptake in the presence or absence of FCCP. Uptake of low concentrations of calcium (0 . 1 mM) was inhibited by the calcium ionophore A23187, but at high calcium concentrations the ionophore stimulated calcium uptake. These observations are explained in terms of a mechanism for the regulation of calcium uptake in spermatozoa based on competing mitochondrial and plasma membrane pumps. Uptake of 32P was also inhibited. These effects provide evidence that cyclic AMP plays a role in the transport of ions across the plasma membrane of spermatozoa."}
{"id": "PMID:220417", "title": "Regulation of cyclic nucleotide phosphodiesterase activity in myometrium from pregnant and spayed rhesus monkeys.", "content": "The activities of myometrial cyclic nucleotide phosphodiesterases (PDEs) and the sensitivity of these enzymes to the effector molecules, cGMP and cAMP, were determined in the 100,000 g supernatant of homogenates from pregnant and spayed rhesus monkeys. The specific activities (per mg nitrogen) of the myometrial cyclic nucleotide PDEs in the supernatant from spayed monkeys were higher than those from pregnant monkeys at all substrate levels studied. However, when calculated on the basis of the DNA content of the myometrium, which was 8 times higher in the spayed than in the pregnant animals, the specific activities were lower in the tissue from spayed animals. At substrate levels of 2 . 5 micron-cAMP, low levels of cGMP (0 . 1-1 . 0 micron) caused the same percentage increase in cGMP-PDE activity in both tissues. At high substrate levels of 100 micron-cAMP, 1 micron-cGMP inhibited only the cAMP-PDE from spayed monkeys, and the enzyme from spayed monkeys was more effectively inhibited by 10 and 40 micron-cGMP than was the enzyme from pregnant animals. The cGMP-PDE activity was inhibited by cAMP (1 . 0-50 . 0 micron), and the percentage inhibition with increasing levels of cAMP appeared to be similar in the two series. The levels of cGMP and cAMP that modify the rate of hydrolysis of the other nucleotide in rhesus myometrium seem to be within the physiological range for these compounds in situ. It therefore appears possible that cAMP and cGMP are each involved in regulating the degradation of the other nucleotide in rhesus myometrium.", "contents": "Regulation of cyclic nucleotide phosphodiesterase activity in myometrium from pregnant and spayed rhesus monkeys. The activities of myometrial cyclic nucleotide phosphodiesterases (PDEs) and the sensitivity of these enzymes to the effector molecules, cGMP and cAMP, were determined in the 100,000 g supernatant of homogenates from pregnant and spayed rhesus monkeys. The specific activities (per mg nitrogen) of the myometrial cyclic nucleotide PDEs in the supernatant from spayed monkeys were higher than those from pregnant monkeys at all substrate levels studied. However, when calculated on the basis of the DNA content of the myometrium, which was 8 times higher in the spayed than in the pregnant animals, the specific activities were lower in the tissue from spayed animals. At substrate levels of 2 . 5 micron-cAMP, low levels of cGMP (0 . 1-1 . 0 micron) caused the same percentage increase in cGMP-PDE activity in both tissues. At high substrate levels of 100 micron-cAMP, 1 micron-cGMP inhibited only the cAMP-PDE from spayed monkeys, and the enzyme from spayed monkeys was more effectively inhibited by 10 and 40 micron-cGMP than was the enzyme from pregnant animals. The cGMP-PDE activity was inhibited by cAMP (1 . 0-50 . 0 micron), and the percentage inhibition with increasing levels of cAMP appeared to be similar in the two series. The levels of cGMP and cAMP that modify the rate of hydrolysis of the other nucleotide in rhesus myometrium seem to be within the physiological range for these compounds in situ. It therefore appears possible that cAMP and cGMP are each involved in regulating the degradation of the other nucleotide in rhesus myometrium."}
{"id": "PMID:220418", "title": "Conjugated and unconjugated oestrogens in fetal and maternal fluids of the cow throughout pregnancy.", "content": "The changes in concentration of oestrone, oestradiol (-17alpha and -17beta), oestrone sulphate and the oestradiol sulphates have been measured in allantoic and amniotic fluids and in maternal peripheral plasma throughout gestation. Oestrone sulphate was the major oestrone present in all of the fluids. It was measurable in allantoic fluid before Day 52 and reached a peak concentration of 475 ng/ml around Day 133. A lower peak occurred in the amniotic fluid around Day 110. The changes in oestradiol sulphates in allantoic fluid were similar to those of oestrone sulphate but at a much lower level. Considerable fluctuation was observed in the oestradiol sulphate concentrations in amniotic fluid. The ratio of oestradiol-17alpha sulphate to oestradiol-17beta sulphate was considerably higher in amniotic fluid than in allantoic fluid. Consistent changes in the levels of oestrone and the oestradiols were found in amniotic fluid but not in allantoic fluid during the second half of pregnancy. In maternal peripheral plasma oestrone sulphate was measurable before Day 72. In the limited number of samples analysed no difference in oestrogen concentration due to the sex of the fetus was evident in any of the fetal or maternal fluids.", "contents": "Conjugated and unconjugated oestrogens in fetal and maternal fluids of the cow throughout pregnancy. The changes in concentration of oestrone, oestradiol (-17alpha and -17beta), oestrone sulphate and the oestradiol sulphates have been measured in allantoic and amniotic fluids and in maternal peripheral plasma throughout gestation. Oestrone sulphate was the major oestrone present in all of the fluids. It was measurable in allantoic fluid before Day 52 and reached a peak concentration of 475 ng/ml around Day 133. A lower peak occurred in the amniotic fluid around Day 110. The changes in oestradiol sulphates in allantoic fluid were similar to those of oestrone sulphate but at a much lower level. Considerable fluctuation was observed in the oestradiol sulphate concentrations in amniotic fluid. The ratio of oestradiol-17alpha sulphate to oestradiol-17beta sulphate was considerably higher in amniotic fluid than in allantoic fluid. Consistent changes in the levels of oestrone and the oestradiols were found in amniotic fluid but not in allantoic fluid during the second half of pregnancy. In maternal peripheral plasma oestrone sulphate was measurable before Day 72. In the limited number of samples analysed no difference in oestrogen concentration due to the sex of the fetus was evident in any of the fetal or maternal fluids."}
{"id": "PMID:220428", "title": "Studies of oligoadenylate formation on a poly (U) template.", "content": "We have studied a variety of condensation reactions involving poly (U) as template and isomeric adenosine dinucleotides as substrates. We find that [3'-5']-linked dinucleotides such as A3pA and pA3pA are better acceptors than the corresponding [2'-5']-linked compounds, while ImpA2pA is a better donor than ImpA3pA. The reaction between A2pA and ImpA3pA, for example, yields only 4% of product while the reaction of A3pA with ImpA2pA yields 86% of product. The more efficient condensation reactions of dimers are about as efficient as the self-condensation of ImpA. They yield a few percent of material in which five or more substrate molecules are linked together. The percentage of the natural [3'-5']-linkage in the product varies greatly, from as little as 1% to as much as 45%.", "contents": "Studies of oligoadenylate formation on a poly (U) template. We have studied a variety of condensation reactions involving poly (U) as template and isomeric adenosine dinucleotides as substrates. We find that [3'-5']-linked dinucleotides such as A3pA and pA3pA are better acceptors than the corresponding [2'-5']-linked compounds, while ImpA2pA is a better donor than ImpA3pA. The reaction between A2pA and ImpA3pA, for example, yields only 4% of product while the reaction of A3pA with ImpA2pA yields 86% of product. The more efficient condensation reactions of dimers are about as efficient as the self-condensation of ImpA. They yield a few percent of material in which five or more substrate molecules are linked together. The percentage of the natural [3'-5']-linkage in the product varies greatly, from as little as 1% to as much as 45%."}
{"id": "PMID:220429", "title": "Women's vaginal responses during REM Sleep.", "content": "Eight female subjects underwent vaginal photoplethysmographic recordings while asleep. Results demonstrated consistent findings of decreases in relative blood volume and increases in relative pulse pressure within the vagina during REM periods. Thes vascular changes indicate that females undergo phasic shifts in vascular blood flow in the vagina during REM sleep, similar to the phasic shifts of blood flow in the male's penis during REM sleep.", "contents": "Women's vaginal responses during REM Sleep. Eight female subjects underwent vaginal photoplethysmographic recordings while asleep. Results demonstrated consistent findings of decreases in relative blood volume and increases in relative pulse pressure within the vagina during REM periods. Thes vascular changes indicate that females undergo phasic shifts in vascular blood flow in the vagina during REM sleep, similar to the phasic shifts of blood flow in the male's penis during REM sleep."}
{"id": "PMID:220430", "title": "Spinal cord compression from metastatic breast carcinoma: treatment by radiation therapy alone.", "content": "There are few reports in the medical literature of treatment of compression of the spinal cord by the use of radiation therapy alone. Laminectomy has been the standard procedure to relieve compression of the spinal cord and should be performed within 48 hours of initial symptoms. In this patient, radiation therapy was the only modality used. It was supplemented by diethylstilbestrol in the course of follow-up. The result of radiotherapy so far has been excellent. The authors emphasize that radiotherapy was begun three months after development of paraplegia, which makes this an interesting case for presentation.", "contents": "Spinal cord compression from metastatic breast carcinoma: treatment by radiation therapy alone. There are few reports in the medical literature of treatment of compression of the spinal cord by the use of radiation therapy alone. Laminectomy has been the standard procedure to relieve compression of the spinal cord and should be performed within 48 hours of initial symptoms. In this patient, radiation therapy was the only modality used. It was supplemented by diethylstilbestrol in the course of follow-up. The result of radiotherapy so far has been excellent. The authors emphasize that radiotherapy was begun three months after development of paraplegia, which makes this an interesting case for presentation."}
{"id": "PMID:220431", "title": "Adenoid cystic carcinoma of breast with metastasis: a case report and review of the literature.", "content": "Adenoid cystic carcinoma of the breast is a rare tumor having a favorable prognosis. At this writing, less than 100 cases have been reported. A review of the literature discloses only six well-documented cases with associated distant metastases. The characteristic biological behavior of this tumor appears to be the development of distant metastasis without prior detectable invasion of axillary lymph nodes.", "contents": "Adenoid cystic carcinoma of breast with metastasis: a case report and review of the literature. Adenoid cystic carcinoma of the breast is a rare tumor having a favorable prognosis. At this writing, less than 100 cases have been reported. A review of the literature discloses only six well-documented cases with associated distant metastases. The characteristic biological behavior of this tumor appears to be the development of distant metastasis without prior detectable invasion of axillary lymph nodes."}
{"id": "PMID:220433", "title": "Treatment of calcium urolithiasis with diphosphonate: efficacy and hazards.", "content": "The effect of treatment of renal stone formation with 5 to 20 mg./kg. per day oral disodium ethane-1-hydroxy-1,1-diphosphonate for up to 30 months was examined in 12 patients with active renal (calcium) stone disease. The over-all incidence of stone passage decreased from 17.8 stones per year per patient before treatment to 7.7 stones per year per patient during therapy. Of the 12 patients 7 passed fewer stones or no stones during treatment. However, the incidence of stone passage was not changed substantially by disodium ethane-1-hydroxy-1,1-diphosphonate in 5 patients. Symptoms of muscle weakness and pain in the back, hips and shoulders occurred in 3 patients during treatment, 2 patients had an increase in serum alkaline phosphatase and 1 patient had a decrease in bone density. Although disodium ethane-1-hydroxy-1,1-diphosphonate may be clinically useful to manage calcium urolithasis in certain patients its over-all use is limited because of its ineffectiveness in some patients and owing to its potential to induce osteomalacia.", "contents": "Treatment of calcium urolithiasis with diphosphonate: efficacy and hazards. The effect of treatment of renal stone formation with 5 to 20 mg./kg. per day oral disodium ethane-1-hydroxy-1,1-diphosphonate for up to 30 months was examined in 12 patients with active renal (calcium) stone disease. The over-all incidence of stone passage decreased from 17.8 stones per year per patient before treatment to 7.7 stones per year per patient during therapy. Of the 12 patients 7 passed fewer stones or no stones during treatment. However, the incidence of stone passage was not changed substantially by disodium ethane-1-hydroxy-1,1-diphosphonate in 5 patients. Symptoms of muscle weakness and pain in the back, hips and shoulders occurred in 3 patients during treatment, 2 patients had an increase in serum alkaline phosphatase and 1 patient had a decrease in bone density. Although disodium ethane-1-hydroxy-1,1-diphosphonate may be clinically useful to manage calcium urolithasis in certain patients its over-all use is limited because of its ineffectiveness in some patients and owing to its potential to induce osteomalacia."}
{"id": "PMID:220434", "title": "Adult Wilms tumor treated with radiotherapy and chemotherapy: a case report.", "content": "A 24-year-old man underwent a left radical nephrectomy for a mass that was found to be a Wilms tumor. The postoperative course, consisting of combined radiotherapy and chemotherapy, is discussed and the recent literature is reviewed.", "contents": "Adult Wilms tumor treated with radiotherapy and chemotherapy: a case report. A 24-year-old man underwent a left radical nephrectomy for a mass that was found to be a Wilms tumor. The postoperative course, consisting of combined radiotherapy and chemotherapy, is discussed and the recent literature is reviewed."}
{"id": "PMID:220440", "title": "Vertical transmission of mouse hepatitis virus infection in mice.", "content": "Transplacental infection with mouse hepatitis virus, JHM strain was studied by intravenous inoculation of pregnant dams. Inoculation on day 9 or 12 of gestation brought about the death of more than 50% of the fetuses at 4 days postinfection while inoculation on day 6 or 15 of gestation effected the death of 12% of fetuses or neonates. Inoculation of day 12 of gestation resulted in markedly higher virus titers. At 72 h postinfection in the placentas, fetal membranes and fetuses than in the maternal livers and blood. Virus-specific antigen and virus particles were noted in the placentas, visceral yolk sac and fetal livers by immunofluorescence and electron microscopy. Histopathology revealed degenerative and necrotic changes in these tissues and in the fetal bone marrow.", "contents": "Vertical transmission of mouse hepatitis virus infection in mice. Transplacental infection with mouse hepatitis virus, JHM strain was studied by intravenous inoculation of pregnant dams. Inoculation on day 9 or 12 of gestation brought about the death of more than 50% of the fetuses at 4 days postinfection while inoculation on day 6 or 15 of gestation effected the death of 12% of fetuses or neonates. Inoculation of day 12 of gestation resulted in markedly higher virus titers. At 72 h postinfection in the placentas, fetal membranes and fetuses than in the maternal livers and blood. Virus-specific antigen and virus particles were noted in the placentas, visceral yolk sac and fetal livers by immunofluorescence and electron microscopy. Histopathology revealed degenerative and necrotic changes in these tissues and in the fetal bone marrow."}
{"id": "PMID:220446", "title": "Nasopharyngeal carcinoma in an Alaskan Eskimo family: report of three cases.", "content": "Nasopharyngeal carcinoma (NPC) has been reported to occur in Alsaka Natives (Eskimos, Indians, and Aleuts) at a rate greater than 15 times the rate for U.S. whites. At least 3 cases of NPC have occurred in close relatives of a Northern Alaskan Eskimo family. All 3 patients had poorly differentiated tumors and have died. Blood groups, HLA antigens, and antibodies to Epstein-Barr virus (EBV) were studied in the family members. EBV titers were elevated in the 1 NPC patient tested and in 1 of 15 other family members tested. All family members studied except 1 were of blood group A, Rh-positive, and HLA types AW24, CW3, CW40/A2, CW2 and B27. This was the first report of more than 2 cases of NPC in a single family in the United States.", "contents": "Nasopharyngeal carcinoma in an Alaskan Eskimo family: report of three cases. Nasopharyngeal carcinoma (NPC) has been reported to occur in Alsaka Natives (Eskimos, Indians, and Aleuts) at a rate greater than 15 times the rate for U.S. whites. At least 3 cases of NPC have occurred in close relatives of a Northern Alaskan Eskimo family. All 3 patients had poorly differentiated tumors and have died. Blood groups, HLA antigens, and antibodies to Epstein-Barr virus (EBV) were studied in the family members. EBV titers were elevated in the 1 NPC patient tested and in 1 of 15 other family members tested. All family members studied except 1 were of blood group A, Rh-positive, and HLA types AW24, CW3, CW40/A2, CW2 and B27. This was the first report of more than 2 cases of NPC in a single family in the United States."}
{"id": "PMID:220447", "title": "Extraction of soluble antigens of Epstein-Barr virus, Herpesvirus salmirl, and Herpesvirus ateles with the use of glycine.", "content": "For extraction of soluble antigen from cells infected with Epstein-Barr virus, Herpesvirus salmirl, and H. ateles, 0.1 M glycine (pH 9.5) was used. This method yielded increased amounts of the antigen containing much less cell debris. Lymphoblastoid cells infected with Epstein-Barr virus could maintain up to 50% viability after the extraction procedure. These cells could be used again after an appropriate interval in culture. The usefulness of this technique is discussed.", "contents": "Extraction of soluble antigens of Epstein-Barr virus, Herpesvirus salmirl, and Herpesvirus ateles with the use of glycine. For extraction of soluble antigen from cells infected with Epstein-Barr virus, Herpesvirus salmirl, and H. ateles, 0.1 M glycine (pH 9.5) was used. This method yielded increased amounts of the antigen containing much less cell debris. Lymphoblastoid cells infected with Epstein-Barr virus could maintain up to 50% viability after the extraction procedure. These cells could be used again after an appropriate interval in culture. The usefulness of this technique is discussed."}
{"id": "PMID:220448", "title": "Preferential inhibition by quercetin of mitogen-stimulated thymocyte glucose transport.", "content": "The ATPase inhibitor quercetin, which inhibits tumor glycolysis, was shown to be a glucose transport inhibitor like the chemically related compound phloretin. Rat thymocyte glucose transport stimulated by the mitogens concanavalin A or ionophore A 23187 was more sensitive than unstimulated transport to quercetin inhibition. The partial inhibition of Na+-, K+- ATPase activity by quercetin observed in tumor cells was confirmed in thymocyte plasma membranes. The specific Na+-, K+- ATPase inhibitor ouabain did not mimic the effect of quercetin on mitogen-stimulated glucose transport but did reduce the effectiveness of concanavalin A as a stimulator of mitochondrial pyruvate oxidation. The results support the idea that glycolytic flux and the activity of plasma membrane ATPase are related but suggest that glucose transport, rather than the Na+-, K+-ATPase, is the  rate-limiting reaction in lymphocytes.", "contents": "Preferential inhibition by quercetin of mitogen-stimulated thymocyte glucose transport. The ATPase inhibitor quercetin, which inhibits tumor glycolysis, was shown to be a glucose transport inhibitor like the chemically related compound phloretin. Rat thymocyte glucose transport stimulated by the mitogens concanavalin A or ionophore A 23187 was more sensitive than unstimulated transport to quercetin inhibition. The partial inhibition of Na+-, K+- ATPase activity by quercetin observed in tumor cells was confirmed in thymocyte plasma membranes. The specific Na+-, K+- ATPase inhibitor ouabain did not mimic the effect of quercetin on mitogen-stimulated glucose transport but did reduce the effectiveness of concanavalin A as a stimulator of mitochondrial pyruvate oxidation. The results support the idea that glycolytic flux and the activity of plasma membrane ATPase are related but suggest that glucose transport, rather than the Na+-, K+-ATPase, is the  rate-limiting reaction in lymphocytes."}
{"id": "PMID:220449", "title": "Inability of antiserum active in antibody-dependent cellular cytotoxicity and arming tests to protect against simian virus 40 tumor cell challenge.", "content": "Previous studies have shown that simian virus 40 (SV40) hamster tumor cells that were pretreated with antiserum from syngeneic hosts sensitized to SV40 were killed following exposure to nonsensitized spleen cells. In this study preincubation of nonadherent spleen or lymph node cells with SV40 antiserum rendered the cells specifically cytotoxic for the SV40-transformed fibroblasts. The capacity of a particular antiserum to \"arm\" (i.e., to be made specifically cytotoxic) was comparable with its ability to mediate antibody-dependent cellular cytotoxicity (ADCC). Experiments were performed to determine if the SV40 antiserum had prophylactic activity. Two hours after passive transfer of serum, cytotoxic effector cells could be demonstrated in the blood, spleen, and mesenteric lymph node, and the recipients' sera were active in ADCC tests. Nevertheless, such hosts were not resistant to challenge with small numbers of SV40 tumor cells that were given intradermally or intracardiacly, nor was tumor growth suppressed by addition of normal lymph node cells to the antiserum-pretreated tumor cell inoculum. Thus SV40 antiserum, active at high titer in ADCC and arming assays, did not prevent or delay growth of SV40 tumor isografts.", "contents": "Inability of antiserum active in antibody-dependent cellular cytotoxicity and arming tests to protect against simian virus 40 tumor cell challenge. Previous studies have shown that simian virus 40 (SV40) hamster tumor cells that were pretreated with antiserum from syngeneic hosts sensitized to SV40 were killed following exposure to nonsensitized spleen cells. In this study preincubation of nonadherent spleen or lymph node cells with SV40 antiserum rendered the cells specifically cytotoxic for the SV40-transformed fibroblasts. The capacity of a particular antiserum to \"arm\" (i.e., to be made specifically cytotoxic) was comparable with its ability to mediate antibody-dependent cellular cytotoxicity (ADCC). Experiments were performed to determine if the SV40 antiserum had prophylactic activity. Two hours after passive transfer of serum, cytotoxic effector cells could be demonstrated in the blood, spleen, and mesenteric lymph node, and the recipients' sera were active in ADCC tests. Nevertheless, such hosts were not resistant to challenge with small numbers of SV40 tumor cells that were given intradermally or intracardiacly, nor was tumor growth suppressed by addition of normal lymph node cells to the antiserum-pretreated tumor cell inoculum. Thus SV40 antiserum, active at high titer in ADCC and arming assays, did not prevent or delay growth of SV40 tumor isografts."}
{"id": "PMID:220452", "title": "Risk of radiation-related subsequent malignant tumors in survivors of Ewing's sarcoma.", "content": "Twenty-four long-term survivors of Ewing's sarcoma were identified as being at risk for a second primary tumor. Among this group of patients followed from 3 to 22 years, 4 new bone tumors were observed, whereas 1.2 x 10(-3) were expected. All new tumors arose in heavily irradiated areas. The risk associated with radiation after 3 years was 7.2 cases/million person-years per rad. The cumulative cancer risk over 10 years for irradiated patients was 35% (SE, 15.1%). Intensive chemotherapy (cyclophosphamide and vincristine administered in five or more courses) seemed to exert an enhancing effect, increasing the rate of development of new tumors.", "contents": "Risk of radiation-related subsequent malignant tumors in survivors of Ewing's sarcoma. Twenty-four long-term survivors of Ewing's sarcoma were identified as being at risk for a second primary tumor. Among this group of patients followed from 3 to 22 years, 4 new bone tumors were observed, whereas 1.2 x 10(-3) were expected. All new tumors arose in heavily irradiated areas. The risk associated with radiation after 3 years was 7.2 cases/million person-years per rad. The cumulative cancer risk over 10 years for irradiated patients was 35% (SE, 15.1%). Intensive chemotherapy (cyclophosphamide and vincristine administered in five or more courses) seemed to exert an enhancing effect, increasing the rate of development of new tumors."}
{"id": "PMID:220453", "title": "Seroepidemiologic studies of bovine papillomavirus infections.", "content": "Bovine and human sera were analyzed for the presence of antibodies against bovine papillomavirus types 1 and 2 (BPV 1 and 2) and human papillomavirus type 1 (HPV 1) in a solid-phase radioimmunoassay. Human sera did not react with BPV antigens, and bovine sera showed no evidence of antibodies against HPV 1. In contrast, 19% of all bovine sera tested reacted with BPV 1 and 2 antigens, and 35% of human sera revealed antibodies against HPV 1. No serologic evidence was obtained for heterologous infections of persons exposed preferentially to cattle (farmers, butchers, and patients with Q-fever).", "contents": "Seroepidemiologic studies of bovine papillomavirus infections. Bovine and human sera were analyzed for the presence of antibodies against bovine papillomavirus types 1 and 2 (BPV 1 and 2) and human papillomavirus type 1 (HPV 1) in a solid-phase radioimmunoassay. Human sera did not react with BPV antigens, and bovine sera showed no evidence of antibodies against HPV 1. In contrast, 19% of all bovine sera tested reacted with BPV 1 and 2 antigens, and 35% of human sera revealed antibodies against HPV 1. No serologic evidence was obtained for heterologous infections of persons exposed preferentially to cattle (farmers, butchers, and patients with Q-fever)."}
{"id": "PMID:220455", "title": "Morphologic characterization of proliferative cells and virus particles in turkeys with lymphoproliferative disease.", "content": "The tumors found in turkeys having lymphoproliferative disease (LPD) are histologically characterized by a pleomorphic population of cells of the lymphoid series. Electron microscopy has shown that, despite marked differences in shape and size, the proliferating cells share basic ultrastructural features, indicating their lymphoid origin. Virus particles morphologically and morphogenetically characteristic of type C oncorna-viruses of Retraviridae were found in different organs and plasma samples of diseased or infected turkeys with LPD. This LPD type C virus resembled members of the reticuloendotheliosis virus group but not members of the avian sarcoma virus group.", "contents": "Morphologic characterization of proliferative cells and virus particles in turkeys with lymphoproliferative disease. The tumors found in turkeys having lymphoproliferative disease (LPD) are histologically characterized by a pleomorphic population of cells of the lymphoid series. Electron microscopy has shown that, despite marked differences in shape and size, the proliferating cells share basic ultrastructural features, indicating their lymphoid origin. Virus particles morphologically and morphogenetically characteristic of type C oncorna-viruses of Retraviridae were found in different organs and plasma samples of diseased or infected turkeys with LPD. This LPD type C virus resembled members of the reticuloendotheliosis virus group but not members of the avian sarcoma virus group."}
{"id": "PMID:220457", "title": "[Effect of strophanthin and cytochrome C on myocardial contraction and the incidence of shock and ventricular fibrillation in experimental myocardial infarct].", "content": "High ligation of the interventricular artery caused ventricular fibrillation in the first 2--4 minutes in 20% of cats. In the remaining animals myocardial contractility diminished to half its initial value. After that, contractility increased gradually. In cardiosclerosis myocardial contractility reduced by 20--30%. Ligation of the interventricular artery on the background of cardiosclerosis induced cardiogenic shock in half of the animals. Cytochrome C does not reduce the diminution of myocardial contractility after ligation and has a marked antifibrillatory effect. Strophantin does not affect the diminution of contractility of a healthy myocardium but reduces the decrease in contractility of a sclerosed myocardium and also promotes the development of ventricular fibrillation following ligation of the interventricular artery.", "contents": "[Effect of strophanthin and cytochrome C on myocardial contraction and the incidence of shock and ventricular fibrillation in experimental myocardial infarct]. High ligation of the interventricular artery caused ventricular fibrillation in the first 2--4 minutes in 20% of cats. In the remaining animals myocardial contractility diminished to half its initial value. After that, contractility increased gradually. In cardiosclerosis myocardial contractility reduced by 20--30%. Ligation of the interventricular artery on the background of cardiosclerosis induced cardiogenic shock in half of the animals. Cytochrome C does not reduce the diminution of myocardial contractility after ligation and has a marked antifibrillatory effect. Strophantin does not affect the diminution of contractility of a healthy myocardium but reduces the decrease in contractility of a sclerosed myocardium and also promotes the development of ventricular fibrillation following ligation of the interventricular artery."}
{"id": "PMID:220458", "title": "[Total cholesterol, triglyceride and alpha-lipoprotein cholesterol levels in the blood of 40- to 59-year-old men in Moscow and Leningrad].", "content": "A population survey of 6.990 males 40--59 years of age living in Moscow and Leningrad was conducted to determine the level of lipids in blood plasma by means of automatic standard biochemical methods. Curves were built of the distribution of the concentration of total cholesterol, triglycerides and alpha-lipoprotein cholesterol, and the average content, the upper levels of the norm (and the lower level of the norm for alpha-lipoprotein cholesterol too) were determined from them. The average content of total cholesterol was 217 mg/100 ml, that of triglycerides 100 mg/100 ml, and that of alpha-lipoprotein cholesterol 50 mg/100 ml. The upper norm levels for total and alpha-lipoprotein cholesterol found by cutting off 10% of the higher values were 270 and 75 mg/100 ml, respectively; the upper norm level for triglycerides (cutting off 5% of the higher values) was 250 mg/100 ml. The lower norm level for alpha-lipoprotein cholesterol (cutting off 10% of the lower values) was 35 mg/100 ml.", "contents": "[Total cholesterol, triglyceride and alpha-lipoprotein cholesterol levels in the blood of 40- to 59-year-old men in Moscow and Leningrad]. A population survey of 6.990 males 40--59 years of age living in Moscow and Leningrad was conducted to determine the level of lipids in blood plasma by means of automatic standard biochemical methods. Curves were built of the distribution of the concentration of total cholesterol, triglycerides and alpha-lipoprotein cholesterol, and the average content, the upper levels of the norm (and the lower level of the norm for alpha-lipoprotein cholesterol too) were determined from them. The average content of total cholesterol was 217 mg/100 ml, that of triglycerides 100 mg/100 ml, and that of alpha-lipoprotein cholesterol 50 mg/100 ml. The upper norm levels for total and alpha-lipoprotein cholesterol found by cutting off 10% of the higher values were 270 and 75 mg/100 ml, respectively; the upper norm level for triglycerides (cutting off 5% of the higher values) was 250 mg/100 ml. The lower norm level for alpha-lipoprotein cholesterol (cutting off 10% of the lower values) was 35 mg/100 ml."}
{"id": "PMID:220459", "title": "Cyclic nucleotide phosphodiesterases in glomeruli of rat renal cortex.", "content": "The presence and properties of cyclic 3',5'-adenosine monophosphate phosphodiesterase (cAMP-PDIE) and cyclic 3',5'-guanosine monophosphate phosphodiesterase (cGMP-PDIE) were studied in glomeruli isolated from rat renal cortex by sieving and density gradient centrifugation. The specific activity of cGMP-PDIE was higher than the specific activity of cAMP-PDIE in glomeruli; in tubules and renal cortical slices, the specific activity of cAMP-PDIE was higher than that of cGMP-PDIE. In homogenates, X 100,000g supernate of homogenate (cytosol) and X 100,000g pellet (membrane fraction) from glomeruli, the specific activity of cGMP-PDIE was significantly higher than it was in analogous preparations from tubules or renal cortical slices. Cyclic 3',5'-GMP (10(-6)M to 10(-5)M) stimulated glomerular cAMP-PDIE, but it was without effect on cAMP-PDIE from tubules. Structural analogs of cyclic 3',5'-GMP or 5'-GMP did not stimulate glomerular cAMP-PDIE. Cyclic 3',5'-AMP slightly inhibited cGMP-PDIE from both glomeruli and tubules. N6-,2'-0-dibutyryl cyclic 3',5'-AMP inhibited cAMP-PDIE, but not cGMP-PDIE. The addition of calcium increased the activity of cGMP-PDIE, mainly in tubules, but was without effect on cAMP-PDIE. These results suggest the predominance of cyclic 3',5'-GMP catabolism in glomeruli in comparison with other cortical structures, and they demonstrate that both the specific activities and regulatory properties of cyclic nucleotide phosphodiesterase in glomeruli differ markedly from tubules or unfractionated renal cortical tissue.", "contents": "Cyclic nucleotide phosphodiesterases in glomeruli of rat renal cortex. The presence and properties of cyclic 3',5'-adenosine monophosphate phosphodiesterase (cAMP-PDIE) and cyclic 3',5'-guanosine monophosphate phosphodiesterase (cGMP-PDIE) were studied in glomeruli isolated from rat renal cortex by sieving and density gradient centrifugation. The specific activity of cGMP-PDIE was higher than the specific activity of cAMP-PDIE in glomeruli; in tubules and renal cortical slices, the specific activity of cAMP-PDIE was higher than that of cGMP-PDIE. In homogenates, X 100,000g supernate of homogenate (cytosol) and X 100,000g pellet (membrane fraction) from glomeruli, the specific activity of cGMP-PDIE was significantly higher than it was in analogous preparations from tubules or renal cortical slices. Cyclic 3',5'-GMP (10(-6)M to 10(-5)M) stimulated glomerular cAMP-PDIE, but it was without effect on cAMP-PDIE from tubules. Structural analogs of cyclic 3',5'-GMP or 5'-GMP did not stimulate glomerular cAMP-PDIE. Cyclic 3',5'-AMP slightly inhibited cGMP-PDIE from both glomeruli and tubules. N6-,2'-0-dibutyryl cyclic 3',5'-AMP inhibited cAMP-PDIE, but not cGMP-PDIE. The addition of calcium increased the activity of cGMP-PDIE, mainly in tubules, but was without effect on cAMP-PDIE. These results suggest the predominance of cyclic 3',5'-GMP catabolism in glomeruli in comparison with other cortical structures, and they demonstrate that both the specific activities and regulatory properties of cyclic nucleotide phosphodiesterase in glomeruli differ markedly from tubules or unfractionated renal cortical tissue."}
{"id": "PMID:220463", "title": "Studies of respiratory disease in random-source laboratory dogs: viral infections in unconditioned dogs.", "content": "A prospective study was conducted to identify the viruses causing respiratory diseases in unconditioned, random-source dogs. During the quarantine period, respiratory disease occurred in 86 of 167 (52%) dogs, and 34 (21%) died. Most affected dogs had a distemper-like illness which required extensive and prolonged care. Histopathologic studies confirmed the diagnosis of canine distemper in 10 of 12 (83%) fatal infections examined. Sixty-seven of 91 (74%) dogs which arrived without canine distemper antibody became ill, and 30 (32%) died. In contrast, only 16 of 67 (24%) dogs with canine distemper antibody had respiratory disease, and only 3 (4%) died. Parainfluenza SV5 and canine adenovirus--type II were recovered from 27 of 54 and 22 of 54 sick dogs, respectively. Canine herpesviruses, canine coronaviruses, and canine parvoviruses were less frequently isolated. Increased antibody titers to SV5 were found consistently, and rises in titer to the other viruses were demonstrated. Many of the sick dogs were infected with two or more viruses. Although several viral agents were detected during these epizootics, prevention of canine distemper appeared to be the key to controlling severe, prolonged, and often fatal respiratory disease.", "contents": "Studies of respiratory disease in random-source laboratory dogs: viral infections in unconditioned dogs. A prospective study was conducted to identify the viruses causing respiratory diseases in unconditioned, random-source dogs. During the quarantine period, respiratory disease occurred in 86 of 167 (52%) dogs, and 34 (21%) died. Most affected dogs had a distemper-like illness which required extensive and prolonged care. Histopathologic studies confirmed the diagnosis of canine distemper in 10 of 12 (83%) fatal infections examined. Sixty-seven of 91 (74%) dogs which arrived without canine distemper antibody became ill, and 30 (32%) died. In contrast, only 16 of 67 (24%) dogs with canine distemper antibody had respiratory disease, and only 3 (4%) died. Parainfluenza SV5 and canine adenovirus--type II were recovered from 27 of 54 and 22 of 54 sick dogs, respectively. Canine herpesviruses, canine coronaviruses, and canine parvoviruses were less frequently isolated. Increased antibody titers to SV5 were found consistently, and rises in titer to the other viruses were demonstrated. Many of the sick dogs were infected with two or more viruses. Although several viral agents were detected during these epizootics, prevention of canine distemper appeared to be the key to controlling severe, prolonged, and often fatal respiratory disease."}
{"id": "PMID:220464", "title": "Isolation of a cytomegalovirus from salivary glands of white-lipped marmosets (Saguinus fuscicollis).", "content": "Minced salivary glands from seven white-lipped marmosets (Saguinus fuscicollis and Saguinus nigricollis) and one cotton-topped marmoset (Saguinus oedipus) were cocultivated with marmoset cell cultures. A viral agent, designated SSG, was isolated from two Saguinus fuscicollis. Slowly progressing foci of rounded, vacuolated, refractile cells were first observed at 40-43 days incubation. Electron microscopy revealed intranuclear herpesvirus nucleocapsids and intracytoplasmic and extracellular enveloped particles. Infected cells stained with hematoxylin and eosin contained eosinophilic intranuclear and cytoplasmic inclusion bodies. SSG could be passaged in cell cultures only using viable whole cells; infectious cell-free virus was not detected in either culture supernatants or cell lysates. SSG replicated in marmoset fibroblastic but not in marmoset epithelioid or human fibroblastic cell cultures. Plasma antibodies to SSG were detected by indirect immunofluorescence assays in 16 of 56 (28.6%) adult wild-caught marmosets but were absent in 40 colony-born, hand-reared marmosets. Antigenic cross-reactivity of SSG with a rhesus monkey (Macaca mulatta) cytomegalovirus (bidirectional) and with a human cytomegalovirus (unidirectional) was also demonstrated by indirect immunofluorescence assays. SSG was identified as a herpesvirus by morphology and was classified as a cytomegalovirus by its site of isolation, biologic properties in vitro, and antigenic characteristics.", "contents": "Isolation of a cytomegalovirus from salivary glands of white-lipped marmosets (Saguinus fuscicollis). Minced salivary glands from seven white-lipped marmosets (Saguinus fuscicollis and Saguinus nigricollis) and one cotton-topped marmoset (Saguinus oedipus) were cocultivated with marmoset cell cultures. A viral agent, designated SSG, was isolated from two Saguinus fuscicollis. Slowly progressing foci of rounded, vacuolated, refractile cells were first observed at 40-43 days incubation. Electron microscopy revealed intranuclear herpesvirus nucleocapsids and intracytoplasmic and extracellular enveloped particles. Infected cells stained with hematoxylin and eosin contained eosinophilic intranuclear and cytoplasmic inclusion bodies. SSG could be passaged in cell cultures only using viable whole cells; infectious cell-free virus was not detected in either culture supernatants or cell lysates. SSG replicated in marmoset fibroblastic but not in marmoset epithelioid or human fibroblastic cell cultures. Plasma antibodies to SSG were detected by indirect immunofluorescence assays in 16 of 56 (28.6%) adult wild-caught marmosets but were absent in 40 colony-born, hand-reared marmosets. Antigenic cross-reactivity of SSG with a rhesus monkey (Macaca mulatta) cytomegalovirus (bidirectional) and with a human cytomegalovirus (unidirectional) was also demonstrated by indirect immunofluorescence assays. SSG was identified as a herpesvirus by morphology and was classified as a cytomegalovirus by its site of isolation, biologic properties in vitro, and antigenic characteristics."}
{"id": "PMID:220465", "title": "Spontaneous liver tumors in aged germfree Wistar rats.", "content": "Liver tumors, ranging from benign nodules to carcinomas, developed spontaneously in 115 (87%) of 132 germfree Wistar rats beyond the age of 30 months. In addition, the rats developed a high incidence of benign adenomas of endocrine glands and of the breasts.", "contents": "Spontaneous liver tumors in aged germfree Wistar rats. Liver tumors, ranging from benign nodules to carcinomas, developed spontaneously in 115 (87%) of 132 germfree Wistar rats beyond the age of 30 months. In addition, the rats developed a high incidence of benign adenomas of endocrine glands and of the breasts."}
{"id": "PMID:220466", "title": "Requirement for guanosine triphosphate in the activation of adenylate cyclase by cholera toxin.", "content": "The activation of adenylate cyclase in lysed pigeon erythrocytes requires, among several cofactors, a nucleotide which may be ATP, GTP, or many other triphosphates. However, after removal of endogenous nucleotides by gel filtration or by adsorption onto charcoal the requirement can be met only by GTP, or an analog of GTP. The GTP is required during the activation of the cyclase by toxin even if GTP is also included during the subsequent adenylate cyclase assay, conducted without toxin. In the presence of GTP it is possible to assay for the cytosolic protein that is also required for the action of cholera toxin. By gel filtration, its apparent molecular weight is 15,000--20,000.", "contents": "Requirement for guanosine triphosphate in the activation of adenylate cyclase by cholera toxin. The activation of adenylate cyclase in lysed pigeon erythrocytes requires, among several cofactors, a nucleotide which may be ATP, GTP, or many other triphosphates. However, after removal of endogenous nucleotides by gel filtration or by adsorption onto charcoal the requirement can be met only by GTP, or an analog of GTP. The GTP is required during the activation of the cyclase by toxin even if GTP is also included during the subsequent adenylate cyclase assay, conducted without toxin. In the presence of GTP it is possible to assay for the cytosolic protein that is also required for the action of cholera toxin. By gel filtration, its apparent molecular weight is 15,000--20,000."}
{"id": "PMID:220467", "title": "Gap junctions and ACTH sensitivity in Y-1 adrenal tumor cells.", "content": "Initial studies of adrenocorticotropin-sensitivity (ACTH-sensitive) and ACTH-insensitive Y-1 adrenal cortical tumor cell lines suggest a relationship between responsiveness to ACTH and the presence of gap junctions. An ACTH-sensitive clone of Y-1 cells possesses gap junctions and these junctions appear to enlarge with ACTH treatment. GAP junctions have not been observed, however, in an ACTH-insensitive clone of Y-1 tumor cells even when stimulated to produce cyclic adenosine monophosphate and steroids with cholera toxin.", "contents": "Gap junctions and ACTH sensitivity in Y-1 adrenal tumor cells. Initial studies of adrenocorticotropin-sensitivity (ACTH-sensitive) and ACTH-insensitive Y-1 adrenal cortical tumor cell lines suggest a relationship between responsiveness to ACTH and the presence of gap junctions. An ACTH-sensitive clone of Y-1 cells possesses gap junctions and these junctions appear to enlarge with ACTH treatment. GAP junctions have not been observed, however, in an ACTH-insensitive clone of Y-1 tumor cells even when stimulated to produce cyclic adenosine monophosphate and steroids with cholera toxin."}
{"id": "PMID:220468", "title": "Pseudo-chondrosarcoma: solitary osseous metastases from atypical bronchogenic carcinoma.", "content": "A patient with bronchogenic carcinoma with a solitary metastases to the femur in whom the clinical, radiologic, and pathologic setting suggested that the primary tumor was the bone lesion (chondrosarcoma) and the pulmonary lesion was a solitary metastasis is presented. This case is added to the limited literature indicating that mucin-secreting tumors metastatic to bone may simulate primary bone tumors radiographically.", "contents": "Pseudo-chondrosarcoma: solitary osseous metastases from atypical bronchogenic carcinoma. A patient with bronchogenic carcinoma with a solitary metastases to the femur in whom the clinical, radiologic, and pathologic setting suggested that the primary tumor was the bone lesion (chondrosarcoma) and the pulmonary lesion was a solitary metastasis is presented. This case is added to the limited literature indicating that mucin-secreting tumors metastatic to bone may simulate primary bone tumors radiographically."}
{"id": "PMID:220469", "title": "Human carcinoma-associated precursor antigens of the NM blood group system.", "content": "Blood group NM specificities occur in healthy, benign and carcinomatous breast glands and those of the gastrointestinal (G.I.) tract, but the precursors in their biosynthesis, T (Thomsen-Friedenreich) and Tn, are found in adenocarcinomata and not in benign or healthy tissues. T- and Tn-antigenic specificities are thus human carcinoma-associated. All humans possess anti-T and anti-Tn antibodies. Patients with breast or G.I. tract carcinoma show statistically significant alteration of anti-T titer levels when compared to patients with benign disease and to healthy controls. Breast carcinoma patients but not healthy people showed cellular immunity to T antigen in vitro and in vivo. Most striking was the delayed-type hypersensitivity reaction, which was positive in over 90% of ductal breast carcinoma patients tested and negative in all presumably healthy individuals. T antigen is readily prepared from healthy human red blood cells in uncontaminated form, and free of HL-A and Au antigens. T antigen and anti-T antibodies may be useful in combating some human adenocarcinomata.", "contents": "Human carcinoma-associated precursor antigens of the NM blood group system. Blood group NM specificities occur in healthy, benign and carcinomatous breast glands and those of the gastrointestinal (G.I.) tract, but the precursors in their biosynthesis, T (Thomsen-Friedenreich) and Tn, are found in adenocarcinomata and not in benign or healthy tissues. T- and Tn-antigenic specificities are thus human carcinoma-associated. All humans possess anti-T and anti-Tn antibodies. Patients with breast or G.I. tract carcinoma show statistically significant alteration of anti-T titer levels when compared to patients with benign disease and to healthy controls. Breast carcinoma patients but not healthy people showed cellular immunity to T antigen in vitro and in vivo. Most striking was the delayed-type hypersensitivity reaction, which was positive in over 90% of ductal breast carcinoma patients tested and negative in all presumably healthy individuals. T antigen is readily prepared from healthy human red blood cells in uncontaminated form, and free of HL-A and Au antigens. T antigen and anti-T antibodies may be useful in combating some human adenocarcinomata."}
{"id": "PMID:220470", "title": "Surgical treatment of recurrent primary malignant tumor of the left atrium.", "content": "A young woman presented with a tumor in the left atrium resembling a left atrial myxoma. After simple excision of the tumor the diagnosis of primary malignant fibrous histiocytoma of the heart was made. A course of radiation therapy was given. Four subsequent recurrences were treated by cardiotomy and resection of the left atrial wall. At the third, fourth, and fifth operations fulguration of the left atrial wall was performed. Subsequent chemotherapy failed to control the tumor. The patient was admitted 6 weeks after the last resection and died. Postmortem examination revealed a large recurrent tumor obstructing the left atrium with no metastases. The clinical course, cardiac catherization data, and postmortem examination are presented. Palliation was achieved by repeated resection of a radiation-resistent primary sarcoma of the heart.", "contents": "Surgical treatment of recurrent primary malignant tumor of the left atrium. A young woman presented with a tumor in the left atrium resembling a left atrial myxoma. After simple excision of the tumor the diagnosis of primary malignant fibrous histiocytoma of the heart was made. A course of radiation therapy was given. Four subsequent recurrences were treated by cardiotomy and resection of the left atrial wall. At the third, fourth, and fifth operations fulguration of the left atrial wall was performed. Subsequent chemotherapy failed to control the tumor. The patient was admitted 6 weeks after the last resection and died. Postmortem examination revealed a large recurrent tumor obstructing the left atrium with no metastases. The clinical course, cardiac catherization data, and postmortem examination are presented. Palliation was achieved by repeated resection of a radiation-resistent primary sarcoma of the heart."}
{"id": "PMID:220472", "title": "New oncogenic human papovaviruses.", "content": "Human papovaviruses of the polyoma-SV40 subgroup are common infectious agents. The clinical picture of the primary infection of these viruses is unknown, but one of the viruses, the JC virus, is associated with and probably causes progressive multifocal leukoencephalopathy. These viruses cause tumours and transform cells of several species of laboratory animals. Current results seem to rule them out as a major aetiollogical factor in human cancer. However, their relationship to human tumours requires further study, especially in immunologically compromised patients showing activation of a latent infection.", "contents": "New oncogenic human papovaviruses. Human papovaviruses of the polyoma-SV40 subgroup are common infectious agents. The clinical picture of the primary infection of these viruses is unknown, but one of the viruses, the JC virus, is associated with and probably causes progressive multifocal leukoencephalopathy. These viruses cause tumours and transform cells of several species of laboratory animals. Current results seem to rule them out as a major aetiollogical factor in human cancer. However, their relationship to human tumours requires further study, especially in immunologically compromised patients showing activation of a latent infection."}
{"id": "PMID:220478", "title": "[Benign tumors of the petrous bone].", "content": "41 benign tumor of the temporal bone are reported. 33 glomustumors, originating from the middle ear or from the lower temporal bone. According to their origin they present different surgical problems. Neurinomas are less common. Surgery is the therapy of choice. Symptoms and properties of these tumors are discussed briefly.", "contents": "[Benign tumors of the petrous bone]. 41 benign tumor of the temporal bone are reported. 33 glomustumors, originating from the middle ear or from the lower temporal bone. According to their origin they present different surgical problems. Neurinomas are less common. Surgery is the therapy of choice. Symptoms and properties of these tumors are discussed briefly."}
{"id": "PMID:220485", "title": "High density lipoproteins, 1978 -- an overview.", "content": "High density lipoproteins (HDL) have come of age. For years it has been fashionable to study HDL as an approach to understanding lipoprotein structure and lipid binding. Available in abundant amounts from normal human plasma, readily separable into its individual lipid and soluble apolipoprotein components, HDL has provided much information for lipoprotein model building. Suddenly it has been thrust center stage clinically by a host of convincing epidemiologic studies that clearly establishes an inverse relationship between HDL levels and coronary vascular events. Biochemists, clinicians, cardiologists and epidemiologists are simultaneously focusing attention on HDL. Familial High Density Lipoprotein Deficiency (Tangier Disease) has been well described but is poorly understood as a clinical syndrome complex. We have suddenly become aware of how little we understand about HDL's normal ultracentrifugal and apoprotein heterogeneity, about its functional role(s) or the determinant(s) of its concentration in plasma. The relative contributions of the two sites of HDL origin, the liver and intestine, are yet to be determined as are the site(s) of degradation. Awareness of a problem and its importance is the first step toward the solution(s) of the problem.", "contents": "High density lipoproteins, 1978 -- an overview. High density lipoproteins (HDL) have come of age. For years it has been fashionable to study HDL as an approach to understanding lipoprotein structure and lipid binding. Available in abundant amounts from normal human plasma, readily separable into its individual lipid and soluble apolipoprotein components, HDL has provided much information for lipoprotein model building. Suddenly it has been thrust center stage clinically by a host of convincing epidemiologic studies that clearly establishes an inverse relationship between HDL levels and coronary vascular events. Biochemists, clinicians, cardiologists and epidemiologists are simultaneously focusing attention on HDL. Familial High Density Lipoprotein Deficiency (Tangier Disease) has been well described but is poorly understood as a clinical syndrome complex. We have suddenly become aware of how little we understand about HDL's normal ultracentrifugal and apoprotein heterogeneity, about its functional role(s) or the determinant(s) of its concentration in plasma. The relative contributions of the two sites of HDL origin, the liver and intestine, are yet to be determined as are the site(s) of degradation. Awareness of a problem and its importance is the first step toward the solution(s) of the problem."}
{"id": "PMID:220486", "title": "The evidence for the antiatherogenicity of high density lipoprotein in man.", "content": "It has long been recognized that patients with clinical coronary heart disease (CHD) have, on average, higher concentrations of plasma very low density and low density lipoproteins than do healthy subjects. The same studies clearly demonstrated that coronary victims tend also to have low plasma concentrations of high density lipoprotein (HDL). It is only recently, however, that the possible significance of this second observation has been examined. Direct evidence for an inverse relationship between HDL cholesterol concentration and the prevalence of clinical CHD, independent of other plasma lipoproteins, has been provided by the Honolulu Heart and Cooperative Lipoprotein Phenotyping Studies. The Troms\u00f8 Heart and Framingham Studies subsequently demonstrated that this relationship precedes the clinical manifestation of coronary disease. More recently, angiographic studies have confirmed that the severity of existing coronary atherosclerosis is inversely related to HDL cholesterol concentration. Other investigations have shown that coronary victims also have low mean concentrations of apolipoproteins AI and AII (the major protein components of HDL), although the reduction of apoAI concentration may be less marked that that of HDL cholesterol, and preliminary findings from Troms\u00f8 have suggested that apolipoprotein AI may be less powerful that HDL cholesterol as a predictor of CHD. Such observations have supported the porposal that HDL may exert a protective effect against coronary atherosclerosis. Final comfirmation (or otherwise) of this hypothesis, however, must await the results of carefully controlled animal experiments and of regression studies in patients with angiogrphically defined atherosclerosis.", "contents": "The evidence for the antiatherogenicity of high density lipoprotein in man. It has long been recognized that patients with clinical coronary heart disease (CHD) have, on average, higher concentrations of plasma very low density and low density lipoproteins than do healthy subjects. The same studies clearly demonstrated that coronary victims tend also to have low plasma concentrations of high density lipoprotein (HDL). It is only recently, however, that the possible significance of this second observation has been examined. Direct evidence for an inverse relationship between HDL cholesterol concentration and the prevalence of clinical CHD, independent of other plasma lipoproteins, has been provided by the Honolulu Heart and Cooperative Lipoprotein Phenotyping Studies. The Troms\u00f8 Heart and Framingham Studies subsequently demonstrated that this relationship precedes the clinical manifestation of coronary disease. More recently, angiographic studies have confirmed that the severity of existing coronary atherosclerosis is inversely related to HDL cholesterol concentration. Other investigations have shown that coronary victims also have low mean concentrations of apolipoproteins AI and AII (the major protein components of HDL), although the reduction of apoAI concentration may be less marked that that of HDL cholesterol, and preliminary findings from Troms\u00f8 have suggested that apolipoprotein AI may be less powerful that HDL cholesterol as a predictor of CHD. Such observations have supported the porposal that HDL may exert a protective effect against coronary atherosclerosis. Final comfirmation (or otherwise) of this hypothesis, however, must await the results of carefully controlled animal experiments and of regression studies in patients with angiogrphically defined atherosclerosis."}
{"id": "PMID:220487", "title": "Ultrastructure of serum high density lipoproteins: facts and models.", "content": "The complexity of the structure of plasma high density lipoproteins (HDL) has invited numerous approaches which have been directed at the study of the intact particles, their apolipoproteins and reassembled complexes. Parameters such as flotation and sedimentation coefficients, size and molecular weight have been determined and in addition, through scattering techniques, an understanding has been obtained on the long range organization between core (cholesteryl esters and triglycerides) and surface components (unesterified cholesterol, phospholipids and apoproteins). In the case of the apolipoproteins, the knowledge of their primary structure has facilitated the study of their physicochemical properties in solution and at the air-water interface and has also permitted realistic predictions of the two dimensional organization, not only of their alpha-helical segments but also of the beta-pleated sheets, random coil and beta-turns, all of which have amphipathic properties. When all of the information from the physical and chemical studies is put together, the various HDL can be described as spherical structures having a liquid core of radius, r - 20.2 A, surrounded by a monolayer of cholesterol and phospholipids with closely packed hydrophobic ends on the surface of the core. The organization of the apoproteins at the lipoprotein interface is comparatively less understood. However, reasonable predictions can be made on secondary structure considerations and on their behavior at the air-water interface. The emerging overall structural information can be translated into a space-filling model that not only provides a useful representation of HDL, but, more importantly, a basis for planning future studies on the elucidation of the structure of these particles on a molecular level.", "contents": "Ultrastructure of serum high density lipoproteins: facts and models. The complexity of the structure of plasma high density lipoproteins (HDL) has invited numerous approaches which have been directed at the study of the intact particles, their apolipoproteins and reassembled complexes. Parameters such as flotation and sedimentation coefficients, size and molecular weight have been determined and in addition, through scattering techniques, an understanding has been obtained on the long range organization between core (cholesteryl esters and triglycerides) and surface components (unesterified cholesterol, phospholipids and apoproteins). In the case of the apolipoproteins, the knowledge of their primary structure has facilitated the study of their physicochemical properties in solution and at the air-water interface and has also permitted realistic predictions of the two dimensional organization, not only of their alpha-helical segments but also of the beta-pleated sheets, random coil and beta-turns, all of which have amphipathic properties. When all of the information from the physical and chemical studies is put together, the various HDL can be described as spherical structures having a liquid core of radius, r - 20.2 A, surrounded by a monolayer of cholesterol and phospholipids with closely packed hydrophobic ends on the surface of the core. The organization of the apoproteins at the lipoprotein interface is comparatively less understood. However, reasonable predictions can be made on secondary structure considerations and on their behavior at the air-water interface. The emerging overall structural information can be translated into a space-filling model that not only provides a useful representation of HDL, but, more importantly, a basis for planning future studies on the elucidation of the structure of these particles on a molecular level."}
{"id": "PMID:220491", "title": "Plasma, apolipoprotein, A-I and A-II levels in hyperlipidemia.", "content": "Some of the component moieties of high density lipoproteins (HDL) were analyzed in normal subjects and in patients with hyperlipidemia. Apoproteins A-I and A-II were quantified by radioimmunoassay, HDL cholesterol and triglycerides were assessed on heparin-MnCl2 supernates of fasting plasmas. We found that HDL is enriched in triglycerides in all forms of hyperlipidemia, while the proportion of ApoA-II is unaltered and the proportion of ApoA-I is decreased. Thus, the composition of HDL is altered in hupertirglyceridemia. The molecular associations of ApoA-I and ApoA-II in plasma were also examined by assaying the apoprotein contents of plasma fractions prepared by ultracentrifugation and by gel filtration column chromatograpy. The ApoA-I contents of d smaller than 1.063 fraction increased in hyperlipidemia from smaller than 0.5% to approximately 2%, but the ApoA-I contents of the d greater than 1.21 fraction remained at less than 12% of total plasmas with triglyceride levels smaller than 1500 mg/dl. d greater than 1.21 ApoA-I rose to 23% in one plasma with a triglyceride level of greater than 1700 mg/dl. On column chromatography, ApoA-I eluted with the lipoproteins and also in a fraction whose molecular weight (MW) appeared to be approximately 50,000 daltons. The proportion of plasma ApoA-I which eluted in the 50,000 MW peak was positively correlated with plasma triglyceride levels, but at triglyceride levels of less than 1500 mg/dl, less than 20% of ApoA-I was in the 50,000 MW peak. Between levels of approximately 2000 and 12,000 mg/dl, the percentage \"50,000 M.W. ApoA-1\" was 20-25%. The ApoA-II contents of d smaller than 1.063 fractions were also increased in hyperlipidemia, but greater than 95% of ApoA-II was found in the HDL fractions in both normal and hyperlipidemic plasma both by column chromatography and ultracentrifugation. Thus, the molecular association of ApoA-I appears to be altered in hyperlipidemia.", "contents": "Plasma, apolipoprotein, A-I and A-II levels in hyperlipidemia. Some of the component moieties of high density lipoproteins (HDL) were analyzed in normal subjects and in patients with hyperlipidemia. Apoproteins A-I and A-II were quantified by radioimmunoassay, HDL cholesterol and triglycerides were assessed on heparin-MnCl2 supernates of fasting plasmas. We found that HDL is enriched in triglycerides in all forms of hyperlipidemia, while the proportion of ApoA-II is unaltered and the proportion of ApoA-I is decreased. Thus, the composition of HDL is altered in hupertirglyceridemia. The molecular associations of ApoA-I and ApoA-II in plasma were also examined by assaying the apoprotein contents of plasma fractions prepared by ultracentrifugation and by gel filtration column chromatograpy. The ApoA-I contents of d smaller than 1.063 fraction increased in hyperlipidemia from smaller than 0.5% to approximately 2%, but the ApoA-I contents of the d greater than 1.21 fraction remained at less than 12% of total plasmas with triglyceride levels smaller than 1500 mg/dl. d greater than 1.21 ApoA-I rose to 23% in one plasma with a triglyceride level of greater than 1700 mg/dl. On column chromatography, ApoA-I eluted with the lipoproteins and also in a fraction whose molecular weight (MW) appeared to be approximately 50,000 daltons. The proportion of plasma ApoA-I which eluted in the 50,000 MW peak was positively correlated with plasma triglyceride levels, but at triglyceride levels of less than 1500 mg/dl, less than 20% of ApoA-I was in the 50,000 MW peak. Between levels of approximately 2000 and 12,000 mg/dl, the percentage \"50,000 M.W. ApoA-1\" was 20-25%. The ApoA-II contents of d smaller than 1.063 fractions were also increased in hyperlipidemia, but greater than 95% of ApoA-II was found in the HDL fractions in both normal and hyperlipidemic plasma both by column chromatography and ultracentrifugation. Thus, the molecular association of ApoA-I appears to be altered in hyperlipidemia."}
{"id": "PMID:220492", "title": "The effect of exercise on plasma high density lipoproteins.", "content": "The influence of vigorous activity in man on plasma lipids and lipoproteins is reviewed, with particular emphasis on high density lipoproteins. Both cross sectional and longitudinal (or training) studies have been reported, many of them of less than ideal design. Nonetheless, a consistent pattern emerges in which increased exercise levels lead to lower plasma concentrations of triglycerides and very low density lipoproteins, and of low density lipoproteins. High density lipoprotein levels increase. Sometimes, but not uniformly, plasma total cholesterol level falls as the result of these changes. The increase in plasma high density lipoprotein appears to be the result largely of an increase in the less dense HDL2 subfraction. Plasma apolipoprotein A-I levels (but not apo-A-II levels) seem to increase concomitantly. The precise biochemical mechanism responsible for these changes has not been elucidated; but the recent finding of increased lipoprotein lipase activity in adipose tissue and muscle of endurance runners suggests that increased lipolytic rate of triglyceride-rich lipoproteins may be an initial step in a sequence of events leading to higher plasma levels of HDL-2.", "contents": "The effect of exercise on plasma high density lipoproteins. The influence of vigorous activity in man on plasma lipids and lipoproteins is reviewed, with particular emphasis on high density lipoproteins. Both cross sectional and longitudinal (or training) studies have been reported, many of them of less than ideal design. Nonetheless, a consistent pattern emerges in which increased exercise levels lead to lower plasma concentrations of triglycerides and very low density lipoproteins, and of low density lipoproteins. High density lipoprotein levels increase. Sometimes, but not uniformly, plasma total cholesterol level falls as the result of these changes. The increase in plasma high density lipoprotein appears to be the result largely of an increase in the less dense HDL2 subfraction. Plasma apolipoprotein A-I levels (but not apo-A-II levels) seem to increase concomitantly. The precise biochemical mechanism responsible for these changes has not been elucidated; but the recent finding of increased lipoprotein lipase activity in adipose tissue and muscle of endurance runners suggests that increased lipolytic rate of triglyceride-rich lipoproteins may be an initial step in a sequence of events leading to higher plasma levels of HDL-2."}
{"id": "PMID:220493", "title": "A review of the unique features of HDL apoproteins.", "content": "The human plasma high density lipoproteins (HDL) are a heterogeneous ensemble of five proteins associated with both neutral and polar lipids. The sequence of all five proteins are known. ApoA-I and apoA-II are the major protein components; apoC-I, apoC-II and apoC-III are the minor protein components. All these apoproteins spontaneously recombine with phospholipids to give stable lipid-protein complexes and freely exchange between the two major HDL subclasses, HDL2 and HDL3. In addition, ApoC-I, apoC-II, and apoC-III exchange between HDL and very low density lipoproteins. Furthermore, certain HDL apoproteins are activators for plasma enzymes that are important in lipid metabolism. ApoA-I and apoC-I activate lecithin/cholesterol acyltransferase; apoC-II is an activator of lipoprotein lipase. The regions of apoC-I and apoC-II that are involved in the activation of these enzymes have been localized with synthetic peptides. Studies of synthetic and native fragments of apoA-II, apoC-I, apoC-II, and apoC-III as well as model lipid-binding peptides have identified specific regions with structural features common to lipid-binding proteins. These special properties, which include helical potential, sequences with a critical amphipathic length, and high hydrophobicity of the nonpolar side of the amphipathic helix, are the determinants of HDL structure and metabolism.", "contents": "A review of the unique features of HDL apoproteins. The human plasma high density lipoproteins (HDL) are a heterogeneous ensemble of five proteins associated with both neutral and polar lipids. The sequence of all five proteins are known. ApoA-I and apoA-II are the major protein components; apoC-I, apoC-II and apoC-III are the minor protein components. All these apoproteins spontaneously recombine with phospholipids to give stable lipid-protein complexes and freely exchange between the two major HDL subclasses, HDL2 and HDL3. In addition, ApoC-I, apoC-II, and apoC-III exchange between HDL and very low density lipoproteins. Furthermore, certain HDL apoproteins are activators for plasma enzymes that are important in lipid metabolism. ApoA-I and apoC-I activate lecithin/cholesterol acyltransferase; apoC-II is an activator of lipoprotein lipase. The regions of apoC-I and apoC-II that are involved in the activation of these enzymes have been localized with synthetic peptides. Studies of synthetic and native fragments of apoA-II, apoC-I, apoC-II, and apoC-III as well as model lipid-binding peptides have identified specific regions with structural features common to lipid-binding proteins. These special properties, which include helical potential, sequences with a critical amphipathic length, and high hydrophobicity of the nonpolar side of the amphipathic helix, are the determinants of HDL structure and metabolism."}
{"id": "PMID:220508", "title": "Organization and expression of a two-gene cluster in the arginine biosynthesis of Saccharomyces cerevisiae.", "content": "In Saccharomyces cerevisiae, argB and argC define two adjacent and complementing loci, with mutants defective in two consecutive steps of arginine biosynthesis: N-acetylglutamate kinase (AG-kinase) and N-acetylglutamyl-phosphate reductase (AGPreductase). These enzymic activities are readily separated by ammonium sulfate fractionation or Sephadex G-200 chromatography. This suggests that each activity is carried in vivo by a different protein. The synthesis of the two enzymes is coordinately regulated, with an 85-fold difference in specific activities between fully repressed and fully derepressed cells. Missence mutations of the argB locus are defective in AGkinase only. Nonsense mutations in the argB locus are defective in both activities. Missense and nonsense mutations in the argC locus are defective in AGPreductase, with a few alleles also showing a reduced level of AGkinase. These data are best explained by assuming that argB and argC are two genes transcribed as a single messenger from argB to argC. This messenger produces in vivo two distinct proteins corresponding to the argB and argC gene products, either because translation can be initiated at the beginning of both genes, or because a large polypeptide is specifically cut in vivo to yield the gene products of argB and argC.", "contents": "Organization and expression of a two-gene cluster in the arginine biosynthesis of Saccharomyces cerevisiae. In Saccharomyces cerevisiae, argB and argC define two adjacent and complementing loci, with mutants defective in two consecutive steps of arginine biosynthesis: N-acetylglutamate kinase (AG-kinase) and N-acetylglutamyl-phosphate reductase (AGPreductase). These enzymic activities are readily separated by ammonium sulfate fractionation or Sephadex G-200 chromatography. This suggests that each activity is carried in vivo by a different protein. The synthesis of the two enzymes is coordinately regulated, with an 85-fold difference in specific activities between fully repressed and fully derepressed cells. Missence mutations of the argB locus are defective in AGkinase only. Nonsense mutations in the argB locus are defective in both activities. Missense and nonsense mutations in the argC locus are defective in AGPreductase, with a few alleles also showing a reduced level of AGkinase. These data are best explained by assuming that argB and argC are two genes transcribed as a single messenger from argB to argC. This messenger produces in vivo two distinct proteins corresponding to the argB and argC gene products, either because translation can be initiated at the beginning of both genes, or because a large polypeptide is specifically cut in vivo to yield the gene products of argB and argC."}
{"id": "PMID:220510", "title": "Spontaneous production of a C-type RNA virus in a cell line derived from rat glioma.", "content": "The spontaneous production of a rat C-type RNA virus (ACV) in a cultured cell line (AC cells) established from a chemically induced rat glioma was studied. The characteristics of ACV were: morphology typical of C-type RNA virus; buoyant density of 1.15 g/ml in a sucrose density gradient; RNA directed DNA polymerase activity; viral core with a density of 1.28 to 1.30 g/ml; 70S RNA with dimer structure; and structural protein composed of mainly four polypeptides. Kinetical analysis of DNA-DNA hybridization revealed that DNA sequences homologous to DNA transcripts of RNA of ACV were present in rat cells. RNA directed DNA polymerase of ACV partially cross-reacted with antiserum to the polymerase of Rauscher murine leukemia virus. These data suggest that ACV is an endogenous C-type RNA virus of rat origin.", "contents": "Spontaneous production of a C-type RNA virus in a cell line derived from rat glioma. The spontaneous production of a rat C-type RNA virus (ACV) in a cultured cell line (AC cells) established from a chemically induced rat glioma was studied. The characteristics of ACV were: morphology typical of C-type RNA virus; buoyant density of 1.15 g/ml in a sucrose density gradient; RNA directed DNA polymerase activity; viral core with a density of 1.28 to 1.30 g/ml; 70S RNA with dimer structure; and structural protein composed of mainly four polypeptides. Kinetical analysis of DNA-DNA hybridization revealed that DNA sequences homologous to DNA transcripts of RNA of ACV were present in rat cells. RNA directed DNA polymerase of ACV partially cross-reacted with antiserum to the polymerase of Rauscher murine leukemia virus. These data suggest that ACV is an endogenous C-type RNA virus of rat origin."}
{"id": "PMID:220514", "title": "Enterovirus infection in a semi-closed community.", "content": "Infection with enteroviruses was studied over a 61-week period (during 1960-61) in a semi-closed child community in the Detention Home of the Allegheny County Juvenile Court in Pittsburgh, Pennsylvania. While most of the viruses isolated were known adeno- and enterovirus types, three apparently represent new enterovirus types or 'prime strains'. Viruses were isolated in all but 6 weeks of the 61-week study period from the gastro-intestinal tracts of 110 children out of a total population of 514 (21%); of these 110, 24 children (22%) excreted virus at the time of admission. The population averaged 37 children (more than half of whom were under 5 years of age), with a turnover of about nine per week. Spread of infection in this community on introduction of a new virus was demonstrated, with virus shedding of variable duration after infection. Thirteen of the 110 positive children (12%) showed mixed virus infections. During the entire study period, no clinical diarrheal illness was found associated with the viral infections detected.", "contents": "Enterovirus infection in a semi-closed community. Infection with enteroviruses was studied over a 61-week period (during 1960-61) in a semi-closed child community in the Detention Home of the Allegheny County Juvenile Court in Pittsburgh, Pennsylvania. While most of the viruses isolated were known adeno- and enterovirus types, three apparently represent new enterovirus types or 'prime strains'. Viruses were isolated in all but 6 weeks of the 61-week study period from the gastro-intestinal tracts of 110 children out of a total population of 514 (21%); of these 110, 24 children (22%) excreted virus at the time of admission. The population averaged 37 children (more than half of whom were under 5 years of age), with a turnover of about nine per week. Spread of infection in this community on introduction of a new virus was demonstrated, with virus shedding of variable duration after infection. Thirteen of the 110 positive children (12%) showed mixed virus infections. During the entire study period, no clinical diarrheal illness was found associated with the viral infections detected."}
{"id": "PMID:220515", "title": "Metronidazole bioassay with increased sensitivity.", "content": "The bioassay of metronidazole using Clostridium butyricum incorporated in agar plates detected concentrations higher than 1.0 microgram/ml. Gentamicin in the sample did not affect the growth of the target organism or the inhibition by metronidazole. Penicillin in the sample could be eliminated by the incorporation of penicillinase in the agar or by using as the target organism a surface inoculum of the penicillin-resistant Bacteroides fragilis. Increasing duration and temperature of aerobic prediffusion before allowing the growth of the strictly anaerobic Cl. butyricum increased the diameters of inhibition by metronidazole, but did not affect the threshold of detectability. The incorporation of metronidazole in the agar increased the sensitivity of the assay ten- to 100-fold.", "contents": "Metronidazole bioassay with increased sensitivity. The bioassay of metronidazole using Clostridium butyricum incorporated in agar plates detected concentrations higher than 1.0 microgram/ml. Gentamicin in the sample did not affect the growth of the target organism or the inhibition by metronidazole. Penicillin in the sample could be eliminated by the incorporation of penicillinase in the agar or by using as the target organism a surface inoculum of the penicillin-resistant Bacteroides fragilis. Increasing duration and temperature of aerobic prediffusion before allowing the growth of the strictly anaerobic Cl. butyricum increased the diameters of inhibition by metronidazole, but did not affect the threshold of detectability. The incorporation of metronidazole in the agar increased the sensitivity of the assay ten- to 100-fold."}
{"id": "PMID:220516", "title": "Prolonged survival in chronic lymphocytic leukemia: a case report.", "content": "A patient with long-standing chronic lymphocytic leukemia with both humoral and cellular immunodeficiency had lymph node receptor evidence of a B lymphocyte disorder. He was also found to secrete the Epstein--Barr virus and, late in his illness, developed a markedly positive antinuclear antibody. Interrelationship of these findings may be important in the ultimate determination of the etiology and functional mechanisms in lymphocyte malignancies.", "contents": "Prolonged survival in chronic lymphocytic leukemia: a case report. A patient with long-standing chronic lymphocytic leukemia with both humoral and cellular immunodeficiency had lymph node receptor evidence of a B lymphocyte disorder. He was also found to secrete the Epstein--Barr virus and, late in his illness, developed a markedly positive antinuclear antibody. Interrelationship of these findings may be important in the ultimate determination of the etiology and functional mechanisms in lymphocyte malignancies."}
{"id": "PMID:220519", "title": "Interrelationship between oxygen consumption, superoxide anion and hydrogen peroxide formation in phagocytosing guinea pig polymorphonuclear leucocytes.", "content": "The paper presents an experimental procedure for a simultaneous assay of oxygen consumption, O2- release and H2O2 accumulation at a very early stage of the respiratory burst that is induced by phagocytosis in guinea pig polymorphonuclear leucocytes. The main findings are as follows: (a) The oxygen consumption that is measurable does not correspond to all oxygen that is reduced. The relationship between the actual oxygen consumed and the amount that is reduced depends on the fate of the intermediate products O2- and H2O2. (b) O2- is measurable extracellularly by the reduction of cytochrome c. When cytochrome c oxidizes the extracellular O2-, molecular oxygen is formed. This fact is shown by a decrease of oxygen consumption. The molar ratio between the O2- detected and the oxygen given back is 1. (c) The amount of O2- released from the cells accounts for only a small part of oxygen actually reduced. (d) H2O2 is detectable only in the presence of NaN3. In this condition almost all oxygen consumed is recovered in the form of H2O2. The molar ratio O2/H2O2 is near unity. The amount of H2O2 derived from dismutation of O2- released is only an aliquot of the total H2O2 accumulated. Thus, most of H2O2 is derived from intracellular sources. (e) In the absence of inhibitors of H2O2 degrading reactions, no detectable accumulation of peroxide occurs. Under these conditions, the main part of H2O2 formed is degraded in almost equal amount by catalase and myeloperoxidase, while only a small aliquot is degraded by NaN3 insensitive reactions.", "contents": "Interrelationship between oxygen consumption, superoxide anion and hydrogen peroxide formation in phagocytosing guinea pig polymorphonuclear leucocytes. The paper presents an experimental procedure for a simultaneous assay of oxygen consumption, O2- release and H2O2 accumulation at a very early stage of the respiratory burst that is induced by phagocytosis in guinea pig polymorphonuclear leucocytes. The main findings are as follows: (a) The oxygen consumption that is measurable does not correspond to all oxygen that is reduced. The relationship between the actual oxygen consumed and the amount that is reduced depends on the fate of the intermediate products O2- and H2O2. (b) O2- is measurable extracellularly by the reduction of cytochrome c. When cytochrome c oxidizes the extracellular O2-, molecular oxygen is formed. This fact is shown by a decrease of oxygen consumption. The molar ratio between the O2- detected and the oxygen given back is 1. (c) The amount of O2- released from the cells accounts for only a small part of oxygen actually reduced. (d) H2O2 is detectable only in the presence of NaN3. In this condition almost all oxygen consumed is recovered in the form of H2O2. The molar ratio O2/H2O2 is near unity. The amount of H2O2 derived from dismutation of O2- released is only an aliquot of the total H2O2 accumulated. Thus, most of H2O2 is derived from intracellular sources. (e) In the absence of inhibitors of H2O2 degrading reactions, no detectable accumulation of peroxide occurs. Under these conditions, the main part of H2O2 formed is degraded in almost equal amount by catalase and myeloperoxidase, while only a small aliquot is degraded by NaN3 insensitive reactions."}
{"id": "PMID:220520", "title": "Some newly characterized collagenases from procaryotes and lower eucaryotes.", "content": "Chemical and enzymatic properties of four collagenases newly isolated from anaerobic Clostridium histolyticum, aerobic Achromobacter iophagus, and from two lower eucaryotes, the fungus Entomophthora coronata and the insect Hypoderma lineatum are reviewed. The problems of their biosynthesis and precursors, namely the effect of induction of collagenase and neutral proteinase in Achromobacter by their macromolecular substrates are discussed. The two bacterial collagenases are Zn-metallo-enzymes; the highly purified Clostridium collagenase contains cyst(e)ine, serine phosphate and tryptophan additionally to amino acids reported previously. Achromobacter collagenase has the highest specific activity of all collagenases; it yields by autolysis enzymatically active degraded forms. The active dimer is composed of two identical subunits of molecular weight 35,000. Similarities between Achromobacter collagenase, thermolysin and Bacillus subtilis neutral proteinase in molecular weight, amino acid composition, and amino acids important for the active sites are discussed. The two collagenases from low eucaryotes are serine proteinases; Hypoderma collagenase is homologous to the trypsin family in the amino terminal sequence. The initial cleavage of native collagen by highly purified bacterial collagenases occurs in the central helical part of the alpha chains and not progressively from the amino terminal end. One of the two initial cleavages produced by Achromobacter collagenase is situated in the region cleaved specifically by vertebrate collagenases, but with different bond specificity. The same is true for the insect collagenase. Entomophthora collagenase is a proteinase of broad specificity which also cleaves collagen in its helical parts. All four collagenases also degrade other proteins according to their bond specificity.", "contents": "Some newly characterized collagenases from procaryotes and lower eucaryotes. Chemical and enzymatic properties of four collagenases newly isolated from anaerobic Clostridium histolyticum, aerobic Achromobacter iophagus, and from two lower eucaryotes, the fungus Entomophthora coronata and the insect Hypoderma lineatum are reviewed. The problems of their biosynthesis and precursors, namely the effect of induction of collagenase and neutral proteinase in Achromobacter by their macromolecular substrates are discussed. The two bacterial collagenases are Zn-metallo-enzymes; the highly purified Clostridium collagenase contains cyst(e)ine, serine phosphate and tryptophan additionally to amino acids reported previously. Achromobacter collagenase has the highest specific activity of all collagenases; it yields by autolysis enzymatically active degraded forms. The active dimer is composed of two identical subunits of molecular weight 35,000. Similarities between Achromobacter collagenase, thermolysin and Bacillus subtilis neutral proteinase in molecular weight, amino acid composition, and amino acids important for the active sites are discussed. The two collagenases from low eucaryotes are serine proteinases; Hypoderma collagenase is homologous to the trypsin family in the amino terminal sequence. The initial cleavage of native collagen by highly purified bacterial collagenases occurs in the central helical part of the alpha chains and not progressively from the amino terminal end. One of the two initial cleavages produced by Achromobacter collagenase is situated in the region cleaved specifically by vertebrate collagenases, but with different bond specificity. The same is true for the insect collagenase. Entomophthora collagenase is a proteinase of broad specificity which also cleaves collagen in its helical parts. All four collagenases also degrade other proteins according to their bond specificity."}
{"id": "PMID:220521", "title": "Differential synthesis of lens proteins in the presence of m7G(5')pppG and cleavage product m7GMP in an embryonic chick lens cell lysate.", "content": "The effect of m7GMP release from m7GMP-containing mRNA cap sequence m7GpppG by the embryonic chick lens m7GpppN-pyrophosphatase activity on the synthesis of lens proteins was examined in a newly developed homologous translation system derived from 15-day embryonic chick lenses. The synthesis of total lens polypeptides and delta-crystallin polypeptides, the major translation product, was inhibited 84% and 88%, respectively, by 0.5 mM m7GpppG; m7GMP (0.5 mM) inhibited total synthesis by 63% but was 33% less inhibitory toward delta-crystallin synthesis; GpppG and GMP were not inhibitors, m7GpppG inhibited met-tRNAfmet incorporation into 80S initiation complexes.", "contents": "Differential synthesis of lens proteins in the presence of m7G(5')pppG and cleavage product m7GMP in an embryonic chick lens cell lysate. The effect of m7GMP release from m7GMP-containing mRNA cap sequence m7GpppG by the embryonic chick lens m7GpppN-pyrophosphatase activity on the synthesis of lens proteins was examined in a newly developed homologous translation system derived from 15-day embryonic chick lenses. The synthesis of total lens polypeptides and delta-crystallin polypeptides, the major translation product, was inhibited 84% and 88%, respectively, by 0.5 mM m7GpppG; m7GMP (0.5 mM) inhibited total synthesis by 63% but was 33% less inhibitory toward delta-crystallin synthesis; GpppG and GMP were not inhibitors, m7GpppG inhibited met-tRNAfmet incorporation into 80S initiation complexes."}
{"id": "PMID:220522", "title": "[Light-dependent paramagnetic center in photosystem 2 of higher plants].", "content": "In subchloroplast fragments of photosystem II from Vicia faba, free from P700 contamination, a free-radical ESR signal (singlet of 9 G peak-to-peak line-width, g approximately 2,0025) appears under illumination in presence of silicomolybdate as electron acceptor. Using ESR-active electron donors and acceptors as well as conventional redox reagents Hill activity of preparations has been evaluated under different conditions. Evidences are presented that the light-induced dark-reversible silicomolybdate-dependent ESR signal is of the same origin as photobleaching centered at 680 nm which has been earlier interpreted as a result of P680 center of photosystem II oxydation. The relaxation properties of this paramagnetic center as measured by microwave power saturation are different from that of P700+-center in photosystem I.", "contents": "[Light-dependent paramagnetic center in photosystem 2 of higher plants]. In subchloroplast fragments of photosystem II from Vicia faba, free from P700 contamination, a free-radical ESR signal (singlet of 9 G peak-to-peak line-width, g approximately 2,0025) appears under illumination in presence of silicomolybdate as electron acceptor. Using ESR-active electron donors and acceptors as well as conventional redox reagents Hill activity of preparations has been evaluated under different conditions. Evidences are presented that the light-induced dark-reversible silicomolybdate-dependent ESR signal is of the same origin as photobleaching centered at 680 nm which has been earlier interpreted as a result of P680 center of photosystem II oxydation. The relaxation properties of this paramagnetic center as measured by microwave power saturation are different from that of P700+-center in photosystem I."}
{"id": "PMID:220523", "title": "[Mechanism of coupling of ion transport and ATP hydrolysis in the Na-pump].", "content": "A generalized scheme of the reaction pathways during activation of the Na,K-ATPase by sodium and potassium ions and a relevant molecular model of the Na-pump are proposed. The model suggests light and heavy enzyme subunits possessing cavities with ion exchange sites. The cavities are of limited size and can contain only 3 sodium or 2 potassium ions. Free energy of ATP hydrolysis is expended on the formation of a special transient nonequilibrium enzyme conformation. In this conformation ion exchange between the subunit cavities becames possible. Na-pump operates as an enthropy machine: the ion movement across the membrane is provided by thermal oscillations of the subunits.", "contents": "[Mechanism of coupling of ion transport and ATP hydrolysis in the Na-pump]. A generalized scheme of the reaction pathways during activation of the Na,K-ATPase by sodium and potassium ions and a relevant molecular model of the Na-pump are proposed. The model suggests light and heavy enzyme subunits possessing cavities with ion exchange sites. The cavities are of limited size and can contain only 3 sodium or 2 potassium ions. Free energy of ATP hydrolysis is expended on the formation of a special transient nonequilibrium enzyme conformation. In this conformation ion exchange between the subunit cavities becames possible. Na-pump operates as an enthropy machine: the ion movement across the membrane is provided by thermal oscillations of the subunits."}
{"id": "PMID:220524", "title": "[Study of the dynamics of water-protein systems by the technic of gamma-resonance spectroscopy].", "content": "The possibility of using gamma resonance spectroscopy (GRS) for studying the dynamics of water-protein systems is shown in the present work. The experiments were carried out on an albumin-water system. The results obtained are compared with those obtained by the spin label method under the same conditions. The different behaviour of Fe ions which are firmly- and weakly-related with the protein matrix allows to separate the mobility of the whole protein macromolecule and also the mobility of its subunits.", "contents": "[Study of the dynamics of water-protein systems by the technic of gamma-resonance spectroscopy]. The possibility of using gamma resonance spectroscopy (GRS) for studying the dynamics of water-protein systems is shown in the present work. The experiments were carried out on an albumin-water system. The results obtained are compared with those obtained by the spin label method under the same conditions. The different behaviour of Fe ions which are firmly- and weakly-related with the protein matrix allows to separate the mobility of the whole protein macromolecule and also the mobility of its subunits."}
{"id": "PMID:220529", "title": "Reproductive capacity and dominant lethal mutations in female guinea-pigs and Djungarian hamsters following X-rays or chemical mutagens.", "content": "The reproductive capacity and induction of dominant lethal mutations in adult female guinea-pigs and Djungarian hamsters were tested following treatment with 400 rad X-rays, 1.6 mg/kg triethylenemelamine (TEM) or 75 mg/kg isopropylmethanesulphonate (IPMS). A fairly high level of dominant lethals were observed in female guinea-pigs mated at the first oestrus after irradiation (23.4 +/- 6.4%) with a lower yield at 3 months (9.6 +/- 8.2%). Neither of the chemicals caused any significant induction of dominant lethals at either mating time. In the reproductive capacity experiments, the mean litter size of irradiated female guinea-pigs was reduced for about 12 months and this was especially marked in the first 6 months following treatment. Neither of the chemicals caused any significant differences in early litter sizes but there was a noticeable reduction in the litter sizes of TEM-treated females in the 18--24 month interval. With Djungarian hamsters a marked effect of X-rays on reproductive capacity was apparent. After 400 rad a smaller proportion of irradiated females littered in the first 25-day interval than after the other treatments, and no irradiated females produced more than one litter. Neither of the chemicals caused such a drastic reduction in fertility but TEM-treated females produced fewer litters and became sterile at an earlier age than control or IPMS-treated females. With IPMS, the number of litters produced was similar to the controls. Both chemicals caused a significant reduction in litter-size but further work is needed to establish whether this was due to induction of dominant lethals. No translocations were observed in the sons of treated female guinea-pigs or hamsters, but the numbers of animals studied were too small for any conclusions to be drawn.", "contents": "Reproductive capacity and dominant lethal mutations in female guinea-pigs and Djungarian hamsters following X-rays or chemical mutagens. The reproductive capacity and induction of dominant lethal mutations in adult female guinea-pigs and Djungarian hamsters were tested following treatment with 400 rad X-rays, 1.6 mg/kg triethylenemelamine (TEM) or 75 mg/kg isopropylmethanesulphonate (IPMS). A fairly high level of dominant lethals were observed in female guinea-pigs mated at the first oestrus after irradiation (23.4 +/- 6.4%) with a lower yield at 3 months (9.6 +/- 8.2%). Neither of the chemicals caused any significant induction of dominant lethals at either mating time. In the reproductive capacity experiments, the mean litter size of irradiated female guinea-pigs was reduced for about 12 months and this was especially marked in the first 6 months following treatment. Neither of the chemicals caused any significant differences in early litter sizes but there was a noticeable reduction in the litter sizes of TEM-treated females in the 18--24 month interval. With Djungarian hamsters a marked effect of X-rays on reproductive capacity was apparent. After 400 rad a smaller proportion of irradiated females littered in the first 25-day interval than after the other treatments, and no irradiated females produced more than one litter. Neither of the chemicals caused such a drastic reduction in fertility but TEM-treated females produced fewer litters and became sterile at an earlier age than control or IPMS-treated females. With IPMS, the number of litters produced was similar to the controls. Both chemicals caused a significant reduction in litter-size but further work is needed to establish whether this was due to induction of dominant lethals. No translocations were observed in the sons of treated female guinea-pigs or hamsters, but the numbers of animals studied were too small for any conclusions to be drawn."}
{"id": "PMID:220525", "title": "[Conformational mobility and functional activity of photosynthetic reaction centers of Rhodopseudomonas sphaeroides].", "content": "In pigment-protein complexes of photosynthetic reaction centres (RC's), extracted from chromatophore membranes of Rps. sphaeroides with sodium dodecylsulphate, functional activity and intramolecular mobility were studied as a function of temperature and hydration by use of the technique of optical absorbance and ESR spectroscopy. Over the studied temperature range from +20 to -120 degrees C and at a relative humidity (P/Ps) from 0.9 to 0.1, there observed a close interrelationship between reversible kinetic changes of direct and backward redox-reactions of the photo-reduced endogeneous acceptor of quinone nature and the effective parameter of the correlation time of the rotational diffusion of the hydrophobic spin probe as well as of spin labels chemically bound to SH- and COOH-groups of amino acid residues of the RC's protein. The findings support the view that the conformational dynamics in the RC controls the effectiveness of the primary processes of stabilization of photochemically separated charges.", "contents": "[Conformational mobility and functional activity of photosynthetic reaction centers of Rhodopseudomonas sphaeroides]. In pigment-protein complexes of photosynthetic reaction centres (RC's), extracted from chromatophore membranes of Rps. sphaeroides with sodium dodecylsulphate, functional activity and intramolecular mobility were studied as a function of temperature and hydration by use of the technique of optical absorbance and ESR spectroscopy. Over the studied temperature range from +20 to -120 degrees C and at a relative humidity (P/Ps) from 0.9 to 0.1, there observed a close interrelationship between reversible kinetic changes of direct and backward redox-reactions of the photo-reduced endogeneous acceptor of quinone nature and the effective parameter of the correlation time of the rotational diffusion of the hydrophobic spin probe as well as of spin labels chemically bound to SH- and COOH-groups of amino acid residues of the RC's protein. The findings support the view that the conformational dynamics in the RC controls the effectiveness of the primary processes of stabilization of photochemically separated charges."}
{"id": "PMID:220534", "title": "Identification of human glandular kallikrein in the beta cell of the pancreas.", "content": "To determine the cellular localization of glandular kallikrein in the human pancreas, immunohistochemical studies were performed with a monospecific antibody against the antigenically identical urinary kallikrein (urokallikrein). The localization of glandular pancreatic kallikrein to the beta cells of the islets was the same as that of insulin in normal human pancreas and in two islet-cell tumors. When beta cells were lacking in islet-cell tumors or in the pancreas of a patient with juvenile-onset diabetes, kallikrein antigen was not detectable. Anti-urokallikrein absorbed with purified urinary or pancreatic kallikrein no longer identified a pancreatic antigen, whereas absorption with insulin had no effect. The beta-cell localization of human pancreatic kallikrein, an endopeptidase that, in concert with carboxypeptidase B, converts bovine proinsulin to a polypeptide with the electrophoretic mobility of insulin, suggests that pancreatic kallikrein may be involved in the physiologic activation of proinsulin.", "contents": "Identification of human glandular kallikrein in the beta cell of the pancreas. To determine the cellular localization of glandular kallikrein in the human pancreas, immunohistochemical studies were performed with a monospecific antibody against the antigenically identical urinary kallikrein (urokallikrein). The localization of glandular pancreatic kallikrein to the beta cells of the islets was the same as that of insulin in normal human pancreas and in two islet-cell tumors. When beta cells were lacking in islet-cell tumors or in the pancreas of a patient with juvenile-onset diabetes, kallikrein antigen was not detectable. Anti-urokallikrein absorbed with purified urinary or pancreatic kallikrein no longer identified a pancreatic antigen, whereas absorption with insulin had no effect. The beta-cell localization of human pancreatic kallikrein, an endopeptidase that, in concert with carboxypeptidase B, converts bovine proinsulin to a polypeptide with the electrophoretic mobility of insulin, suggests that pancreatic kallikrein may be involved in the physiologic activation of proinsulin."}
{"id": "PMID:220530", "title": "Myasthenia gravis: a personal view of pathogenesis and mechanism, part 2.", "content": "A review of our current knowledge of the etiology and pathogenesis of myasthenia gravis is presented, with particular emphasis on the immunological aspects of the disease. Part 1, published in the January/February issue of MUSCLE & NERVE, dealt with the clinical and genetic features of myasthenia gravis which led to the autoimmune theory of the etiology of the disease. Part 2, which appears in this issue, provides a review of the dysfunction of physiology, pharmacology, and structure of the neuromuscular junction in myasthenia gravis, and the part played by the autoimmune process.", "contents": "Myasthenia gravis: a personal view of pathogenesis and mechanism, part 2. A review of our current knowledge of the etiology and pathogenesis of myasthenia gravis is presented, with particular emphasis on the immunological aspects of the disease. Part 1, published in the January/February issue of MUSCLE & NERVE, dealt with the clinical and genetic features of myasthenia gravis which led to the autoimmune theory of the etiology of the disease. Part 2, which appears in this issue, provides a review of the dysfunction of physiology, pharmacology, and structure of the neuromuscular junction in myasthenia gravis, and the part played by the autoimmune process."}
{"id": "PMID:220531", "title": "Sural nerve conduction study in the rat: a new technique for studying experimental neuropathies.", "content": "An electrophysiologic technique for studying sensory fibers in the rat sural nerve is described. The conduction velocity of the sural nerve in rats is much slower than in humans, probably because of lack of large myelinated nerve fibers in rats. An experimental neuropathy (induced by hexachlorophene) that predominantly causes a myelin disorder produced a slowing of sural nerve conduction velocity and a potential of normal amplitude and duration. An experimental neuropathy (induced by zinc pyrithione) that primarily causes axonal degeneration produced a sensory potential of lower amplitude and shorter duration that had a normal conduction velocity.", "contents": "Sural nerve conduction study in the rat: a new technique for studying experimental neuropathies. An electrophysiologic technique for studying sensory fibers in the rat sural nerve is described. The conduction velocity of the sural nerve in rats is much slower than in humans, probably because of lack of large myelinated nerve fibers in rats. An experimental neuropathy (induced by hexachlorophene) that predominantly causes a myelin disorder produced a slowing of sural nerve conduction velocity and a potential of normal amplitude and duration. An experimental neuropathy (induced by zinc pyrithione) that primarily causes axonal degeneration produced a sensory potential of lower amplitude and shorter duration that had a normal conduction velocity."}
{"id": "PMID:220536", "title": "Controlled clinical trial of prophylactic human-leukocyte interferon in renal transplantation. Effects on cytomegalovirus and herpes simplex virus infections.", "content": "A double-blind, placebo-controlled trial of interferon prophylaxis against viral infections was conducted in renal-transplant recipients receiving standard immunosuprressive therapy with or without antithymocyte globulin. Interferon was administered for six weeks, beginning on the day of transplantation. Cytomegalovirus excretion began earlier and viremia was more frequent in placebo-treated than in interferon-treated patients. Cytomegalovirus viremia correlated with clinical syndromes was more frequent in recipients of antithymocyte globulin. In contrast, neither interferon nor antithymocyte globulin altered excretion of herpes simplex virus. Reversible leukopenia and thrombocytopenia occurred in seven interferon recipients. Patient and graft survival were comparable in interferon and placebo groups. There preliminary results suggest that a six-week course of prophylactic interferon delays shedding of cytomegalovirus and decreases the incidence of viremia after transplantation. In contrast, antithymocyte globulin appears to increase the severity of infection from cytomegalovirus among these patients.", "contents": "Controlled clinical trial of prophylactic human-leukocyte interferon in renal transplantation. Effects on cytomegalovirus and herpes simplex virus infections. A double-blind, placebo-controlled trial of interferon prophylaxis against viral infections was conducted in renal-transplant recipients receiving standard immunosuprressive therapy with or without antithymocyte globulin. Interferon was administered for six weeks, beginning on the day of transplantation. Cytomegalovirus excretion began earlier and viremia was more frequent in placebo-treated than in interferon-treated patients. Cytomegalovirus viremia correlated with clinical syndromes was more frequent in recipients of antithymocyte globulin. In contrast, neither interferon nor antithymocyte globulin altered excretion of herpes simplex virus. Reversible leukopenia and thrombocytopenia occurred in seven interferon recipients. Patient and graft survival were comparable in interferon and placebo groups. There preliminary results suggest that a six-week course of prophylactic interferon delays shedding of cytomegalovirus and decreases the incidence of viremia after transplantation. In contrast, antithymocyte globulin appears to increase the severity of infection from cytomegalovirus among these patients."}
{"id": "PMID:220533", "title": "Lumbar plexus neuropathy resulting from retroperitoneal hemorrhage.", "content": "A case of lumbar plexus neuropathy occurring in the setting of heparin therapy is reported. Documentation of the site of a retroperitoneal hematoma by CT scan was made prior to the full clinical evolution of lumbar plexus neuropathy resulting from a psoas-muscle hematoma. Two patterns of retroperitoneal bleeding and their respective clinical manifestations are discussed. Early diagnosis of these syndromes may allow for intervention before neurologic compromise is established.", "contents": "Lumbar plexus neuropathy resulting from retroperitoneal hemorrhage. A case of lumbar plexus neuropathy occurring in the setting of heparin therapy is reported. Documentation of the site of a retroperitoneal hematoma by CT scan was made prior to the full clinical evolution of lumbar plexus neuropathy resulting from a psoas-muscle hematoma. Two patterns of retroperitoneal bleeding and their respective clinical manifestations are discussed. Early diagnosis of these syndromes may allow for intervention before neurologic compromise is established."}
{"id": "PMID:220532", "title": "Peripheral neuropathy in lead-intoxicated sickle cell patients.", "content": "Peripheral neuropathy and hypertension caused by lead intoxication are reported in two children with sickle cell anemia. One child had generalized weakness in the initial occurrence and distal paralysis during a relapse two years later. The second child had foot and wrist drop. Both had slow peripheral nerve conduction velocities during the episodes. Chelation therapy was successful and resulted in a return of strength (over a period of several months) and a normalization of the blood pressures. Children with sickle cell anemia who are subjected to lead intoxication appear to be predisposed to peripheral nerve damage.", "contents": "Peripheral neuropathy in lead-intoxicated sickle cell patients. Peripheral neuropathy and hypertension caused by lead intoxication are reported in two children with sickle cell anemia. One child had generalized weakness in the initial occurrence and distal paralysis during a relapse two years later. The second child had foot and wrist drop. Both had slow peripheral nerve conduction velocities during the episodes. Chelation therapy was successful and resulted in a return of strength (over a period of several months) and a normalization of the blood pressures. Children with sickle cell anemia who are subjected to lead intoxication appear to be predisposed to peripheral nerve damage."}
{"id": "PMID:220538", "title": "Ringworm of the African hedgehog (Erinaceus albiventris) in the Ivory Coast due to Arthroderma benhamiae.", "content": "Isolates of the conidial state of Arthroderma behnhamiae (+ mating strain) were obtained from dry, scaly lesions on the ears of 3 hedgehogs in the Ivory Coast. This is a new record for this country.", "contents": "Ringworm of the African hedgehog (Erinaceus albiventris) in the Ivory Coast due to Arthroderma benhamiae. Isolates of the conidial state of Arthroderma behnhamiae (+ mating strain) were obtained from dry, scaly lesions on the ears of 3 hedgehogs in the Ivory Coast. This is a new record for this country."}
{"id": "PMID:220539", "title": "Local aggregation of hormone-receptor complexes is required for activation by epidermal growth factor.", "content": "An analogue of epidermal growth factor (EGF) which is virtually devoid of biological activity retains receptor binding activity but cannot form cell surface clusters or patches. Bivalent anti-EGF antibodies restore both bioactivity and patch formation. The sensitivity of fibroblasts to native EGF can also be enhanced greatly by these antibodies, especially in hormone-resistant cell lines.", "contents": "Local aggregation of hormone-receptor complexes is required for activation by epidermal growth factor. An analogue of epidermal growth factor (EGF) which is virtually devoid of biological activity retains receptor binding activity but cannot form cell surface clusters or patches. Bivalent anti-EGF antibodies restore both bioactivity and patch formation. The sensitivity of fibroblasts to native EGF can also be enhanced greatly by these antibodies, especially in hormone-resistant cell lines."}
{"id": "PMID:220541", "title": "Cell-surface antigens induced by RNA tumour viruses.", "content": "Host animals show an immune response to the surface of cells infected with RNA tumour viruses. An element of this response is due to expression of viral structural antigens, but the major part is due to virus-induced cell-surface antigens (CSAs). This article compares the properties of CSAs of the avian, murine and feline retrovirus systems.", "contents": "Cell-surface antigens induced by RNA tumour viruses. Host animals show an immune response to the surface of cells infected with RNA tumour viruses. An element of this response is due to expression of viral structural antigens, but the major part is due to virus-induced cell-surface antigens (CSAs). This article compares the properties of CSAs of the avian, murine and feline retrovirus systems."}
{"id": "PMID:220544", "title": "Effect of posture on the plasma concentrations of aldosterone in hypertension and primary hyperaldosteronism.", "content": "Measurement of plasma aldosterone concentrations (PAC) at 8 a.m. and after 4 h in the upright posture can further assist in identifying the adrenal pathologic lesion in patients with primary aldosteronism. Increases in PAC are associated with hyperplasia, and decreases with adenoma. Normal increases in response to upright posture are observed in patients with essential hypertension with normal or reduced renin concentration.", "contents": "Effect of posture on the plasma concentrations of aldosterone in hypertension and primary hyperaldosteronism. Measurement of plasma aldosterone concentrations (PAC) at 8 a.m. and after 4 h in the upright posture can further assist in identifying the adrenal pathologic lesion in patients with primary aldosteronism. Increases in PAC are associated with hyperplasia, and decreases with adenoma. Normal increases in response to upright posture are observed in patients with essential hypertension with normal or reduced renin concentration."}
{"id": "PMID:220545", "title": "Neural control of renal tubular sodium reabsorption.", "content": "Renal adrenergic nerves are in contact with the basement membranes of tubule cells and, when these nerves are stimulated or ablated, proximal tubular reabsorption of sodium is increased or decreased, respectively. Renal adrenergic nerve activity appears to be regulated by low-pressure cardiopulmonary receptors and high-pressure arterial baroreceptors in response to changes in blood volume. Thus, a decrease in blood volume or in effective circulating blood volume leads to an increase in renal nerve activity, release of norepinephrine, alpha-adrenergic stimulation and increased tubular reabsorption of sodium, whereas an increase in blood volume leads to a decrease in renal nerve activity, a decreased release of norepinephrine, an increased release of dopamine, possible beta-adrenergic stimulation and a decreased tubular reabsorption of sodium.", "contents": "Neural control of renal tubular sodium reabsorption. Renal adrenergic nerves are in contact with the basement membranes of tubule cells and, when these nerves are stimulated or ablated, proximal tubular reabsorption of sodium is increased or decreased, respectively. Renal adrenergic nerve activity appears to be regulated by low-pressure cardiopulmonary receptors and high-pressure arterial baroreceptors in response to changes in blood volume. Thus, a decrease in blood volume or in effective circulating blood volume leads to an increase in renal nerve activity, release of norepinephrine, alpha-adrenergic stimulation and increased tubular reabsorption of sodium, whereas an increase in blood volume leads to a decrease in renal nerve activity, a decreased release of norepinephrine, an increased release of dopamine, possible beta-adrenergic stimulation and a decreased tubular reabsorption of sodium."}
{"id": "PMID:220546", "title": "Cortisol secretion after hemorrhage: multiple mechanisms.", "content": "Multiple mechanisms appear to be involved in mediation of increased secretion of cortisol after hemorrhage. Signals from cardiovascular receptors are transmitted to the hypothalamus through ascending neural pathways to release ACTH. Angiotensin II stimulates release of ACTH by an action on the median eminence, but does not stimulate adrenal secretion of cortisol directly. However, secretion of cortisol can increase rapidly after hemorrhage without changes in ACTH. Common afferent pathways probably mediate all these mechanisms.", "contents": "Cortisol secretion after hemorrhage: multiple mechanisms. Multiple mechanisms appear to be involved in mediation of increased secretion of cortisol after hemorrhage. Signals from cardiovascular receptors are transmitted to the hypothalamus through ascending neural pathways to release ACTH. Angiotensin II stimulates release of ACTH by an action on the median eminence, but does not stimulate adrenal secretion of cortisol directly. However, secretion of cortisol can increase rapidly after hemorrhage without changes in ACTH. Common afferent pathways probably mediate all these mechanisms."}
{"id": "PMID:220547", "title": "Growth characteristics in patients with Bartter's syndrome.", "content": "Studies on the growth and development of patients with Bartter's syndrome indicate that severe growth retardation occurs during infancy and early childhood. Delayed adolescent growth spurt has occurred in all patients studied thus far who had manifested the syndrome during infancy. Normal stature is eventually attained. Mental development ranges from normal to brain damage and dysfunction; however, the majority of patients show some degree of mental retardation. The coexistence of Leigh's encephalopathy with Bartter's syndrome in one patient and the finding of severe motor and congnitive retardation with communicating hydrocephalus in another indicate that the prognosis of mental development in some cases of Bartter's syndrome is guarded. Particular attention should be given to maintaining normal nutritional status in all patients, particularly during infancy and early childhood.", "contents": "Growth characteristics in patients with Bartter's syndrome. Studies on the growth and development of patients with Bartter's syndrome indicate that severe growth retardation occurs during infancy and early childhood. Delayed adolescent growth spurt has occurred in all patients studied thus far who had manifested the syndrome during infancy. Normal stature is eventually attained. Mental development ranges from normal to brain damage and dysfunction; however, the majority of patients show some degree of mental retardation. The coexistence of Leigh's encephalopathy with Bartter's syndrome in one patient and the finding of severe motor and congnitive retardation with communicating hydrocephalus in another indicate that the prognosis of mental development in some cases of Bartter's syndrome is guarded. Particular attention should be given to maintaining normal nutritional status in all patients, particularly during infancy and early childhood."}
{"id": "PMID:220548", "title": "Nephrogenous cyclic AMP as a parathyroid function test.", "content": "In man, the total amount of cyclic AMP (cAMP) excreted in urine is derived from (a) the filtered load of the nucleotide and (b) cAMP formed de novo in the kidney (nephrogenous cAMP, NcAMP). NcAMP is the only pool of the nucleotide easily quantified in vivo and appears to provide a specific index of the effects of circulating, active parathyroid hormone. Elevated values for NcAMP (4.64 +/- 1.95 nmol/100 ml GF, mean +/- SD) were found in 90% or more of 115 patients with primary hyperparathyroidism, and low values (0.31 +/- 0.16 nmol/100 ml GF, mean +/- SD) were noted in 41 individuals with absent or suppressed parathyroid function. When properly expressed (as a function of glomerular filtration rate), results for the total cAMP excretion provided similar findings. The measurement of NcAMP provides a sensitive index of parathyroid function over the entire range of parathyroid activity and has proven to be an optimal method for assessing parathyroid suppressibility in response to intravenous or oral calcium administration. These techniques, the 'calcium injection test' and the 'oral calcium tolerance test', are useful in evaluation a number of subtle disorders of calcium metabolism.", "contents": "Nephrogenous cyclic AMP as a parathyroid function test. In man, the total amount of cyclic AMP (cAMP) excreted in urine is derived from (a) the filtered load of the nucleotide and (b) cAMP formed de novo in the kidney (nephrogenous cAMP, NcAMP). NcAMP is the only pool of the nucleotide easily quantified in vivo and appears to provide a specific index of the effects of circulating, active parathyroid hormone. Elevated values for NcAMP (4.64 +/- 1.95 nmol/100 ml GF, mean +/- SD) were found in 90% or more of 115 patients with primary hyperparathyroidism, and low values (0.31 +/- 0.16 nmol/100 ml GF, mean +/- SD) were noted in 41 individuals with absent or suppressed parathyroid function. When properly expressed (as a function of glomerular filtration rate), results for the total cAMP excretion provided similar findings. The measurement of NcAMP provides a sensitive index of parathyroid function over the entire range of parathyroid activity and has proven to be an optimal method for assessing parathyroid suppressibility in response to intravenous or oral calcium administration. These techniques, the 'calcium injection test' and the 'oral calcium tolerance test', are useful in evaluation a number of subtle disorders of calcium metabolism."}
{"id": "PMID:220549", "title": "Kidney stones: various forms and treatment.", "content": "Calcium urolithasis is not a homogeneous entity, but is a result of many etiologies, with different physicochemical and physiological backgrounds. This diversity of presentation requires an appreciation of specific diagnostic criteria, and a selection of an appropriate treatment regimen for each cause.", "contents": "Kidney stones: various forms and treatment. Calcium urolithasis is not a homogeneous entity, but is a result of many etiologies, with different physicochemical and physiological backgrounds. This diversity of presentation requires an appreciation of specific diagnostic criteria, and a selection of an appropriate treatment regimen for each cause."}
{"id": "PMID:220550", "title": "Control of aldosterone secretion.", "content": "This paper reviews the control of aldosterone secretion, including the role played by hepatic metabolic clearance, ACTH, and the renin-angiotensin system, and the interrelationships of aldosterone secretion with sodium and potassium metabolism. The physiological modulations of aldosterone secretion by the upright posture, progesterone, estriol and estradiol are also discussed.", "contents": "Control of aldosterone secretion. This paper reviews the control of aldosterone secretion, including the role played by hepatic metabolic clearance, ACTH, and the renin-angiotensin system, and the interrelationships of aldosterone secretion with sodium and potassium metabolism. The physiological modulations of aldosterone secretion by the upright posture, progesterone, estriol and estradiol are also discussed."}
{"id": "PMID:220551", "title": "Different effects of K+ and Ca++ on alpha-MSH and ACTH release from superfused neurointermediate lobe of the rat hypophysis.", "content": "The effects of K+-enhanced and Ca++-free media on alpha-MSH and adrenocorticotropic hormone (ACTH) release from superfused neurointermediate lobe (NIL) were studied in the same experiments. High K+ caused reversible and repeatable inhibition of alpha-MSH release and stimulation of ACTH release, Removal of Ca++ impaired the effect of K+, irreversibly for alpha-MSH and reversibly for ACTH. The existence of both melanotrophic and corticotrophic cells within the intermediate lobe (IL) of rat hypophysis could account for the different effects of ionic modifications on in vitro alpha-MSH and ACTH release.", "contents": "Different effects of K+ and Ca++ on alpha-MSH and ACTH release from superfused neurointermediate lobe of the rat hypophysis. The effects of K+-enhanced and Ca++-free media on alpha-MSH and adrenocorticotropic hormone (ACTH) release from superfused neurointermediate lobe (NIL) were studied in the same experiments. High K+ caused reversible and repeatable inhibition of alpha-MSH release and stimulation of ACTH release, Removal of Ca++ impaired the effect of K+, irreversibly for alpha-MSH and reversibly for ACTH. The existence of both melanotrophic and corticotrophic cells within the intermediate lobe (IL) of rat hypophysis could account for the different effects of ionic modifications on in vitro alpha-MSH and ACTH release."}
{"id": "PMID:220552", "title": "Inhibition of adrenocorticotrophin secretion during deprivation-induced eating and drinking in rats.", "content": "Rats that were maintained on a 23-h food and water deprivation schedule (food and water available between 09:00 and 10:00 h) for 21 days, and whose blood was sampled at various times following initiation of ingestion showed a decrease in plasma adrenocorticotrophin (ACTH) concurrent with dropping plasma levels of corticosterone (COR). This drop occurred from elevated levels of these hormones, most likely due to altered circadian patterns of pituitary-adrenal activity as a result of the rhythm-entraining properties of the feeding schedule. This inhibition of secretion of ACTH is interpreted as reflecting the inhibitory effect of a central nervous system mechanism that can affect ACTH secretion independently of corticosteroid negative feedback.", "contents": "Inhibition of adrenocorticotrophin secretion during deprivation-induced eating and drinking in rats. Rats that were maintained on a 23-h food and water deprivation schedule (food and water available between 09:00 and 10:00 h) for 21 days, and whose blood was sampled at various times following initiation of ingestion showed a decrease in plasma adrenocorticotrophin (ACTH) concurrent with dropping plasma levels of corticosterone (COR). This drop occurred from elevated levels of these hormones, most likely due to altered circadian patterns of pituitary-adrenal activity as a result of the rhythm-entraining properties of the feeding schedule. This inhibition of secretion of ACTH is interpreted as reflecting the inhibitory effect of a central nervous system mechanism that can affect ACTH secretion independently of corticosteroid negative feedback."}
{"id": "PMID:220560", "title": "Anticonvulsant and anesthetic barbiturates: different postsynaptic actions in cultured mammalian neurons.", "content": "Mammalian spinal cord neurons were grown in dissociated cell culture and used to study the effects of the anticonvulsant barbiturates phenobarbital and mephobarbital, and the anesthetic barbiturates pentobarbital, secobarbital, and 1,3-dimethyl-butylethyl barbituric acid on amino acid responses and neuronal membrane properties. All barbiturates augmented responses to GABA and diminished glutamate (GLU) responses, but the anesthetic barbiturates were more potent. The anesthetic barbiturates directly depressed excitability by increasing membrane conductance, an effect reversed by the GABA antagonists picrotoxin and penicillin. Anticonvulsant barbiturates, however, had only minimal GABA-mimetic inhibitory action at high doses. Modulation of synaptic events mediated by GABA and GLU might contribute to barbiturate anticonvulsant activity; and direct GABA-mimetic inhibition, combined with similar modulation of synaptic transmission, might underlie barbiturate anesthesia.", "contents": "Anticonvulsant and anesthetic barbiturates: different postsynaptic actions in cultured mammalian neurons. Mammalian spinal cord neurons were grown in dissociated cell culture and used to study the effects of the anticonvulsant barbiturates phenobarbital and mephobarbital, and the anesthetic barbiturates pentobarbital, secobarbital, and 1,3-dimethyl-butylethyl barbituric acid on amino acid responses and neuronal membrane properties. All barbiturates augmented responses to GABA and diminished glutamate (GLU) responses, but the anesthetic barbiturates were more potent. The anesthetic barbiturates directly depressed excitability by increasing membrane conductance, an effect reversed by the GABA antagonists picrotoxin and penicillin. Anticonvulsant barbiturates, however, had only minimal GABA-mimetic inhibitory action at high doses. Modulation of synaptic events mediated by GABA and GLU might contribute to barbiturate anticonvulsant activity; and direct GABA-mimetic inhibition, combined with similar modulation of synaptic transmission, might underlie barbiturate anesthesia."}
{"id": "PMID:220561", "title": "Neurologic disturbances in Paget disease of bone: response to calcitonin.", "content": "The neurologic manifestations of Paget disease and the therapeutic effect of calcitonin were studied in 49 patients. Twenty-four patients (49%) had neurologic disorders involving cranial nerves other than the auditory system, brainstem, spinal cord, or spinal roots and nerves. Eighteen of the 24 patients (75%) showed significant subjective or objective improvement after calcitonin treatment. The effect of calcitonin treatment on spinal cord compression was dramatic in three of six patients. The observations made of these patients support previous data suggesting that the neurologic signs and symptoms of Paget disease have their pathogenesis in both mechanical impingement and vascular distortion. The importance of early detection of neurologic signs and symptoms is emphasized, since prompt treatment with calcitonin may prevent severe complications.", "contents": "Neurologic disturbances in Paget disease of bone: response to calcitonin. The neurologic manifestations of Paget disease and the therapeutic effect of calcitonin were studied in 49 patients. Twenty-four patients (49%) had neurologic disorders involving cranial nerves other than the auditory system, brainstem, spinal cord, or spinal roots and nerves. Eighteen of the 24 patients (75%) showed significant subjective or objective improvement after calcitonin treatment. The effect of calcitonin treatment on spinal cord compression was dramatic in three of six patients. The observations made of these patients support previous data suggesting that the neurologic signs and symptoms of Paget disease have their pathogenesis in both mechanical impingement and vascular distortion. The importance of early detection of neurologic signs and symptoms is emphasized, since prompt treatment with calcitonin may prevent severe complications."}
{"id": "PMID:220562", "title": "Cholinergic dysautonomia and Eaton-Lambert syndrome.", "content": "Cholinergic autonomic function was abnormal in a 47-year-old woman with Eaton-Lambert syndrome (ELS), not associated with carcinoma. Pupillary constriction to light and accommodation, sweating, lacrimation, and salivation were all affected. There was no evidence of Sjogren syndrome or botulinum intoxication. The defect of acetylcholine release from presynaptic terminals in the Eaton-Lambert syndrome may not be restricted to the neuromuscular junction of skeletal muscle.", "contents": "Cholinergic dysautonomia and Eaton-Lambert syndrome. Cholinergic autonomic function was abnormal in a 47-year-old woman with Eaton-Lambert syndrome (ELS), not associated with carcinoma. Pupillary constriction to light and accommodation, sweating, lacrimation, and salivation were all affected. There was no evidence of Sjogren syndrome or botulinum intoxication. The defect of acetylcholine release from presynaptic terminals in the Eaton-Lambert syndrome may not be restricted to the neuromuscular junction of skeletal muscle."}
{"id": "PMID:220563", "title": "Perhexiline maleate and peripheral neuropathy.", "content": "Peripheral neuropathy has been noted as a complication of therapy with perhexiline maleate, a drug widely used in France (and in clinical trials in the United States) for the prophylactic treatment of angina pectoris. In 24 patients with this complication, the marked slowing of motor nerve conduction velocity and the electromyographic changes imply mainly a demyelinating disorder. Improvement was noted with cessation of therapy. In a few cases the presence of active denervation signified a poor prognosis, with only slight improvement. The underlying mechanism causing the neuropathy is not yet fully known, although some evidence indicates that it may be a lipid storage process.", "contents": "Perhexiline maleate and peripheral neuropathy. Peripheral neuropathy has been noted as a complication of therapy with perhexiline maleate, a drug widely used in France (and in clinical trials in the United States) for the prophylactic treatment of angina pectoris. In 24 patients with this complication, the marked slowing of motor nerve conduction velocity and the electromyographic changes imply mainly a demyelinating disorder. Improvement was noted with cessation of therapy. In a few cases the presence of active denervation signified a poor prognosis, with only slight improvement. The underlying mechanism causing the neuropathy is not yet fully known, although some evidence indicates that it may be a lipid storage process."}
{"id": "PMID:220567", "title": "[Survival and therapy of multiple myeloma. Apropos of 56 observed cases].", "content": "56 cases of myeloma observed since 1956 are reviewed and it is noted that course, prognosis and survival have changed in relation to the improvement in diagnostic procedures and therapeutic aids. The recent introduction of polychemotherapeutic approaches based on theoretical considerations has not yet been fully vetted in the clinic although a higher percentage of remissions compared to that obtained by monochemotherapy would seem to be confirmed. Personal experience with a new polychemotherapeutic schema in advanced myeloma resistant to monochemotherapy + prednisone is reported.", "contents": "[Survival and therapy of multiple myeloma. Apropos of 56 observed cases]. 56 cases of myeloma observed since 1956 are reviewed and it is noted that course, prognosis and survival have changed in relation to the improvement in diagnostic procedures and therapeutic aids. The recent introduction of polychemotherapeutic approaches based on theoretical considerations has not yet been fully vetted in the clinic although a higher percentage of remissions compared to that obtained by monochemotherapy would seem to be confirmed. Personal experience with a new polychemotherapeutic schema in advanced myeloma resistant to monochemotherapy + prednisone is reported."}
{"id": "PMID:220568", "title": "[Case studies of the histological characterization of primary tumors of the testis].", "content": "One hundred-ninety nine cases of testicular tumours, of which 189 (94,9%) germ cell tumours, have been studied by histological methods. Seminoma with its two subtypes (anaplastic and spermatocytic) is the most frequent tumour (110 cases i.e. 55,2%), followed by embryonal carcinoma (30 cases: 15,3%), teratocarcinoma (25 cases: 13,2%), teratoma (12 cases: 6,3%) and choriocarcinoma (5 cases: 2,6%). Tumours showing more than one histologic pattern are frequent. The distinctive histologic features have studied, with emphasis of those useful for diagnostic and prognostic purposes. The ages mostly involved by various tumours are stressed. The rarest tumours are briefly described. Histologic data suggest that germinal tumours are originated by the same primordial germ cell which is able to develop various degrees of differentiation. Histologic and histogenetic features of limphomas and tumours of specialized gonadal stroma are also discussed.", "contents": "[Case studies of the histological characterization of primary tumors of the testis]. One hundred-ninety nine cases of testicular tumours, of which 189 (94,9%) germ cell tumours, have been studied by histological methods. Seminoma with its two subtypes (anaplastic and spermatocytic) is the most frequent tumour (110 cases i.e. 55,2%), followed by embryonal carcinoma (30 cases: 15,3%), teratocarcinoma (25 cases: 13,2%), teratoma (12 cases: 6,3%) and choriocarcinoma (5 cases: 2,6%). Tumours showing more than one histologic pattern are frequent. The distinctive histologic features have studied, with emphasis of those useful for diagnostic and prognostic purposes. The ages mostly involved by various tumours are stressed. The rarest tumours are briefly described. Histologic data suggest that germinal tumours are originated by the same primordial germ cell which is able to develop various degrees of differentiation. Histologic and histogenetic features of limphomas and tumours of specialized gonadal stroma are also discussed."}
{"id": "PMID:220571", "title": "24-hour patterns of blood sugar, plasma insulin and free fatty acids in patients with primary endogenous hyperlipoproteinemia on isocaloric diets containing 30, 40 and 79 cal% carbohydrates.", "content": "10 patients with primary, endogenous hypertriglyceridemia (type IV hyperlipoproteinemia) underwent three different isocaloric dietary regimes of 10 days duration each. The diets contained either 30, 43 or 79% of calories as carbohydrate with 20% of calories from protein. Analyses of insulin, blood sugar and free fatty acids were conducted on the last day of each dietary period, at frequent intervals. There were no differences in either fasting or diurnal blood sugars with the different diets. Insulin levels were positively correlated with the amount of carbohydrate in the diet and there was an inverse correlation between the carbohydrate contents of the diets and circulating free fatty acid levels during waking hours. Since glucose tolerance is maintained, and diurnal plasma lipid levels are lowest with the low fat regime, such diets may be advantageously used for patients with endogenous hypertriglyceridemia.", "contents": "24-hour patterns of blood sugar, plasma insulin and free fatty acids in patients with primary endogenous hyperlipoproteinemia on isocaloric diets containing 30, 40 and 79 cal% carbohydrates. 10 patients with primary, endogenous hypertriglyceridemia (type IV hyperlipoproteinemia) underwent three different isocaloric dietary regimes of 10 days duration each. The diets contained either 30, 43 or 79% of calories as carbohydrate with 20% of calories from protein. Analyses of insulin, blood sugar and free fatty acids were conducted on the last day of each dietary period, at frequent intervals. There were no differences in either fasting or diurnal blood sugars with the different diets. Insulin levels were positively correlated with the amount of carbohydrate in the diet and there was an inverse correlation between the carbohydrate contents of the diets and circulating free fatty acid levels during waking hours. Since glucose tolerance is maintained, and diurnal plasma lipid levels are lowest with the low fat regime, such diets may be advantageously used for patients with endogenous hypertriglyceridemia."}
{"id": "PMID:220573", "title": "Endometrial pathology and estrogens.", "content": "Endometrial biopsies were obtained from 46 hypogonadal patients (44 with gonadal dysgenesis; 2 panhypopituitary) who were receiving estrogen-progestogen therapy. Endometrial abnormalities occurred only in patients receiving a total lifetime conjugated estrogen dose of greater than or equal to 2500 mg and who had received estrogen treatment for a period longer than 4.2 years. The biopsy outcome was significantly related (P less than 0.01) to the estrogen dose at time of biopsy and to the total lifetime dose (P less than 0.05). The progestational drugs administered did not protect against development of endometrial abnormalities. None of the abnormal endometrial patterns were associated with abnormal vaginal bleeding.", "contents": "Endometrial pathology and estrogens. Endometrial biopsies were obtained from 46 hypogonadal patients (44 with gonadal dysgenesis; 2 panhypopituitary) who were receiving estrogen-progestogen therapy. Endometrial abnormalities occurred only in patients receiving a total lifetime conjugated estrogen dose of greater than or equal to 2500 mg and who had received estrogen treatment for a period longer than 4.2 years. The biopsy outcome was significantly related (P less than 0.01) to the estrogen dose at time of biopsy and to the total lifetime dose (P less than 0.05). The progestational drugs administered did not protect against development of endometrial abnormalities. None of the abnormal endometrial patterns were associated with abnormal vaginal bleeding."}
{"id": "PMID:220574", "title": "Benign gestational trophoblastic disease metastatic to pleura: unusual cause of hemothorax.", "content": "A unique case of hemothorax caused by proven pleural involvement with benign gestational trophoblastic disease and anticoagulation is presented. The pulmonary manifestations of gestational trophoblastic disease are reviewed. It is stressed that these may be associated with histologically benign as well as frankly malignant disease, and that the clinician must be alert for them in managing all patients with known or suspected gestational trophoblastic disease.", "contents": "Benign gestational trophoblastic disease metastatic to pleura: unusual cause of hemothorax. A unique case of hemothorax caused by proven pleural involvement with benign gestational trophoblastic disease and anticoagulation is presented. The pulmonary manifestations of gestational trophoblastic disease are reviewed. It is stressed that these may be associated with histologically benign as well as frankly malignant disease, and that the clinician must be alert for them in managing all patients with known or suspected gestational trophoblastic disease."}
{"id": "PMID:220575", "title": "Heterologous mixed m\u00fcllerian tumor confined to an endometrial polyp.", "content": "Mixed m\u00fcllerian tumors of the uterus, which have been divided into homologous and heterologous types, are considered neoplasms of high malignant potential. In the heterologous variety, the presence of rhabdomyosarcoma has been associated with an especially poor prognosis. We report the first case of a heterologous, malignant mixed mesodermal tumor (adenocarcinoma, stromal sarcoma, and rhabdomyosarcoma) confined to an endometrial polyp. The patient, treated by surgery only, remains clinically free of disease 11 years later. Mixed m\u00fcllerian tumors of limited extent may not be associated with the dismal prognosis that usually accompanies such lesions.", "contents": "Heterologous mixed m\u00fcllerian tumor confined to an endometrial polyp. Mixed m\u00fcllerian tumors of the uterus, which have been divided into homologous and heterologous types, are considered neoplasms of high malignant potential. In the heterologous variety, the presence of rhabdomyosarcoma has been associated with an especially poor prognosis. We report the first case of a heterologous, malignant mixed mesodermal tumor (adenocarcinoma, stromal sarcoma, and rhabdomyosarcoma) confined to an endometrial polyp. The patient, treated by surgery only, remains clinically free of disease 11 years later. Mixed m\u00fcllerian tumors of limited extent may not be associated with the dismal prognosis that usually accompanies such lesions."}
{"id": "PMID:220578", "title": "Preliminary characterization of viruses isolated from cases of epididymitis and vaginitis in cattle.", "content": "Twelve slow-growing virus isolates propagated in tissue culture from cattle with epididymitis and vaginitis were identified as herpes viruses by virtue of their biological, physicochemical and morphological characteristics. None of the 12 virus strains proved to be serologically related to the infectious pustular vulvo-vaginitis-infectious bovine rhinotracheitis (IPV-IBR) virus, but a further 3 strains included in this study were identical with IPV-IBR virus. Three of the slow-growing virus strains caused a mild anterior vaginitis when deposited in the vagina of heifers. A pool of 10 slow-growing viruses plus a strain of IPV-IBR virus produced anterior and posterior vaginitis in a heifer. the results are discussed in the light of the original description of vaginitis in the \"epivag\" syndrome.", "contents": "Preliminary characterization of viruses isolated from cases of epididymitis and vaginitis in cattle. Twelve slow-growing virus isolates propagated in tissue culture from cattle with epididymitis and vaginitis were identified as herpes viruses by virtue of their biological, physicochemical and morphological characteristics. None of the 12 virus strains proved to be serologically related to the infectious pustular vulvo-vaginitis-infectious bovine rhinotracheitis (IPV-IBR) virus, but a further 3 strains included in this study were identical with IPV-IBR virus. Three of the slow-growing virus strains caused a mild anterior vaginitis when deposited in the vagina of heifers. A pool of 10 slow-growing viruses plus a strain of IPV-IBR virus produced anterior and posterior vaginitis in a heifer. the results are discussed in the light of the original description of vaginitis in the \"epivag\" syndrome."}
{"id": "PMID:220579", "title": "Non-Hodgkin's lymphoma of the hard palate.", "content": "In the past decades many changes have taken place in the classification of lymphoreticular malignancies. At present two main groups are recognized--Hodgkin's lymphomas and non-Hodgkin's lymphomas. Hodgkin's lymphomas rarely affect the oral cavity. The mouth, especially the soft tissues, is somewhat more frequently involved in cases of non-Hodgkin's lymphoma. There seems to be some predilection for the mucosa of the palate. The present report describes eight patients in whom a swelling of the palatal mucosa led to the diagnosis of non-Hodgkin's lymphoma. The emphasis is on the clinical and microscopic aspects. The present most accepted histologic classifications have been applied and are briefly discussed.", "contents": "Non-Hodgkin's lymphoma of the hard palate. In the past decades many changes have taken place in the classification of lymphoreticular malignancies. At present two main groups are recognized--Hodgkin's lymphomas and non-Hodgkin's lymphomas. Hodgkin's lymphomas rarely affect the oral cavity. The mouth, especially the soft tissues, is somewhat more frequently involved in cases of non-Hodgkin's lymphoma. There seems to be some predilection for the mucosa of the palate. The present report describes eight patients in whom a swelling of the palatal mucosa led to the diagnosis of non-Hodgkin's lymphoma. The emphasis is on the clinical and microscopic aspects. The present most accepted histologic classifications have been applied and are briefly discussed."}
{"id": "PMID:220584", "title": "Neonatal herpes simplex infection possibly acquired via maternal breast milk.", "content": "A newborn infant with disseminated herpes simplex virus type 1 (HSV-1) infection was determined serologically to have acquired the infection postnatally; his mother was found to have HSV-1 in her breast milk but had no history of genital lesions and negative viral cultures of cervix, vagina, and throat. We suggest that HSV-infected maternal breast milk may be a source of this infection for susceptible infants.", "contents": "Neonatal herpes simplex infection possibly acquired via maternal breast milk. A newborn infant with disseminated herpes simplex virus type 1 (HSV-1) infection was determined serologically to have acquired the infection postnatally; his mother was found to have HSV-1 in her breast milk but had no history of genital lesions and negative viral cultures of cervix, vagina, and throat. We suggest that HSV-infected maternal breast milk may be a source of this infection for susceptible infants."}
{"id": "PMID:220585", "title": "Growth increments with low dose intermittent growth hormone and fluoxymesterone in first year of therapy in hypopituitarism.", "content": "The availability of a commercial preparation of human growth hormone (hGH) prompted a study in children with hypopituitarism to determine the efficacy of a lower dose of hGH. Thirteen children, ages 4 years 3 months to 13 years 7 months, were given hGH concomitant with fluoxymesterone in an intermittent regimen. The hGH was given intramuscularly, 1 IU daily for 12 to 36 days in each course. There were four courses per year. The fluoxymesterone was given orally, 1 to 2 mg. The total amount of hGH administered was between 48 and 112 IU per year, as compared with the regimen of 312 IU per year, 2 units three times a week. The growth velocity in all 13 children improved, and the mean growth velocity was 6.4 cm +/- 1.13 SD. The mean bone age increment was 0.57 years +/- 0.14 SEM in one chronological year of therapy. The low dose regimen permits a significant reduction in cost of hGH without causing undue advance in bone age.", "contents": "Growth increments with low dose intermittent growth hormone and fluoxymesterone in first year of therapy in hypopituitarism. The availability of a commercial preparation of human growth hormone (hGH) prompted a study in children with hypopituitarism to determine the efficacy of a lower dose of hGH. Thirteen children, ages 4 years 3 months to 13 years 7 months, were given hGH concomitant with fluoxymesterone in an intermittent regimen. The hGH was given intramuscularly, 1 IU daily for 12 to 36 days in each course. There were four courses per year. The fluoxymesterone was given orally, 1 to 2 mg. The total amount of hGH administered was between 48 and 112 IU per year, as compared with the regimen of 312 IU per year, 2 units three times a week. The growth velocity in all 13 children improved, and the mean growth velocity was 6.4 cm +/- 1.13 SD. The mean bone age increment was 0.57 years +/- 0.14 SEM in one chronological year of therapy. The low dose regimen permits a significant reduction in cost of hGH without causing undue advance in bone age."}
{"id": "PMID:220582", "title": "[Ultrastructure of the cyst wall of Aploparakis polystictae and A. furcigera (Cestoda, Cyclophyllidaea) metacestodes].", "content": "The development of the additional membrane (exocyst) from the caudal appendage in diplocysts does not change essentially the structure of the cyst's wall in metacestodes of the genus Aploparaksis. In cytoplasmic connections between cytons and the surface syncytium there are two autonomous enough systems of transport: microtubes opening to the surface of tegument and matrix of bridges which proceed to the matrix of external syncytium. In addition to cytons, in the cyst's wall there are cells with an enlarged granulated endoplasmic network, which are miofibroblasts, secretory cells performing an unclear function, protonephridia and cells limiting the cavity of the cyst of the layer. Differences in the larval morphology of both species are quite negligible and can be due to their age peculiarities.", "contents": "[Ultrastructure of the cyst wall of Aploparakis polystictae and A. furcigera (Cestoda, Cyclophyllidaea) metacestodes]. The development of the additional membrane (exocyst) from the caudal appendage in diplocysts does not change essentially the structure of the cyst's wall in metacestodes of the genus Aploparaksis. In cytoplasmic connections between cytons and the surface syncytium there are two autonomous enough systems of transport: microtubes opening to the surface of tegument and matrix of bridges which proceed to the matrix of external syncytium. In addition to cytons, in the cyst's wall there are cells with an enlarged granulated endoplasmic network, which are miofibroblasts, secretory cells performing an unclear function, protonephridia and cells limiting the cavity of the cyst of the layer. Differences in the larval morphology of both species are quite negligible and can be due to their age peculiarities."}
{"id": "PMID:220586", "title": "Ketotic hypoglycemia and hypopituitarism.", "content": "A 5-year-old girl had hypoglycemia and was of short stature. Studies of pituitary function demonstrated combined growth hormone and adrenocorticotropic hormone (ACTH) deficiency. She was shown to have ketotic hypoglycemia. In contrast to patients previously reported with hypopituitarism and ketotic hypoglycemia, she had no deficiency of gluconeogenic substrate. Serum levels of alanine and other gluconeogenic amino acids were normal during fasting and hypoglycemia. These studies suggest that inadequate gluconeogenic precursors are not the cause of her ketotic hypoglycemia. Ketotic hypoglycemia in association with hypopituitarism may be secondary to multiple biochemical defects.", "contents": "Ketotic hypoglycemia and hypopituitarism. A 5-year-old girl had hypoglycemia and was of short stature. Studies of pituitary function demonstrated combined growth hormone and adrenocorticotropic hormone (ACTH) deficiency. She was shown to have ketotic hypoglycemia. In contrast to patients previously reported with hypopituitarism and ketotic hypoglycemia, she had no deficiency of gluconeogenic substrate. Serum levels of alanine and other gluconeogenic amino acids were normal during fasting and hypoglycemia. These studies suggest that inadequate gluconeogenic precursors are not the cause of her ketotic hypoglycemia. Ketotic hypoglycemia in association with hypopituitarism may be secondary to multiple biochemical defects."}
{"id": "PMID:220583", "title": "Learning capacities during sleep: a preliminary study in a group of schizophrenic inpatients.", "content": "The relationship between sleep and learning processes is analysed in a sample of schizophrenic patients, starting from more recent hypotheses about the function of REM sleep in learning and memory processes. This is done by means of two experiments: in the first AA. evaluate the possibility to elicit a simple motor conditional reflex acquired during daytime in different sleep stages. With the second experiment daytime learning performances are evaluated with and without a reinforcement administered during REM sleep. Results for the first experiment underline a qualitative difference between REM and nREM sleep in a reflexological perspective. In nREM sleep the conditional response is better maintained than in REM sleep. The second experiment confirms the possibility to improve daytime learning performances after an additional presentation of learning material in REM. The joint study of sleep abnormalities and learning and cognitive impairment in schizophrenic patients is finally suggested.", "contents": "Learning capacities during sleep: a preliminary study in a group of schizophrenic inpatients. The relationship between sleep and learning processes is analysed in a sample of schizophrenic patients, starting from more recent hypotheses about the function of REM sleep in learning and memory processes. This is done by means of two experiments: in the first AA. evaluate the possibility to elicit a simple motor conditional reflex acquired during daytime in different sleep stages. With the second experiment daytime learning performances are evaluated with and without a reinforcement administered during REM sleep. Results for the first experiment underline a qualitative difference between REM and nREM sleep in a reflexological perspective. In nREM sleep the conditional response is better maintained than in REM sleep. The second experiment confirms the possibility to improve daytime learning performances after an additional presentation of learning material in REM. The joint study of sleep abnormalities and learning and cognitive impairment in schizophrenic patients is finally suggested."}
{"id": "PMID:220591", "title": "Comparison of theoretical denaturation maps of phiX174 and SV40 with their gene maps.", "content": "When the theoretical denaturation maps of phiX174 and SV40 are compared with their gene maps, it is observed that the beginning and the end of each gene in these two DNA's fall in a region of lower melting temperatures. Local (A+T)-contents evaluated from the known sequences at these regions support the above implication that the beginnings and the ends of nearly all the genes in phiX174 and SV40 are relatively rich in (A+T)-content.", "contents": "Comparison of theoretical denaturation maps of phiX174 and SV40 with their gene maps. When the theoretical denaturation maps of phiX174 and SV40 are compared with their gene maps, it is observed that the beginning and the end of each gene in these two DNA's fall in a region of lower melting temperatures. Local (A+T)-contents evaluated from the known sequences at these regions support the above implication that the beginnings and the ends of nearly all the genes in phiX174 and SV40 are relatively rich in (A+T)-content."}
{"id": "PMID:220592", "title": "Recovery of DNA synthesis after ultraviolet irradiation of xeroderma pigmentosum cells depends on excision repair and is blocked by caffeine.", "content": "Normal human and xeroderma pigmentosum (XP, excision-defective group A) cells (both SV40-transformed) pulse-labeled with [(3)H]thymidine at various times after irradiation with ultraviolet light showed a decline and recovery of both the molecular weights of newly synthesized DNA and the rates of synthesis per cell. At the same ultraviolet dose, both molecular weights and rates of synthesis were inhibited more in XP than in normal cells. This indicates that excision repair plays a role in minimizing the inhibition of chain growth, possibly by excision of dimers ahead of the growing point. The ability to synthesize normal-sized DNA recovered more rapidly than rates of synthesis in normal cells, but both parameters recovered in phase in XP cells. During recovery in normal cells there are therefore fewer actively replicating clusters of replicons because the single-strand breaks involved in the excision of dimers inhibit replicon initiation. XP cells have few excision repair events and therefore fewer breaks to interfere with initiation, but chain growth is blocked by unexcised dimers. In both cell types recovery of the ability to synthesize normal-sized DNA was prevented by growing cells in caffeine after irradiation, possibly because of competition between the DNA binding properties of caffeine and replication proteins. Our observations imply that excision repair and semiconservative replication interact strongly in irradiated cells to produce a complex spectrum of changes in DNA replication which may be confused with parts of alternative systems such as post-replication repair.", "contents": "Recovery of DNA synthesis after ultraviolet irradiation of xeroderma pigmentosum cells depends on excision repair and is blocked by caffeine. Normal human and xeroderma pigmentosum (XP, excision-defective group A) cells (both SV40-transformed) pulse-labeled with [(3)H]thymidine at various times after irradiation with ultraviolet light showed a decline and recovery of both the molecular weights of newly synthesized DNA and the rates of synthesis per cell. At the same ultraviolet dose, both molecular weights and rates of synthesis were inhibited more in XP than in normal cells. This indicates that excision repair plays a role in minimizing the inhibition of chain growth, possibly by excision of dimers ahead of the growing point. The ability to synthesize normal-sized DNA recovered more rapidly than rates of synthesis in normal cells, but both parameters recovered in phase in XP cells. During recovery in normal cells there are therefore fewer actively replicating clusters of replicons because the single-strand breaks involved in the excision of dimers inhibit replicon initiation. XP cells have few excision repair events and therefore fewer breaks to interfere with initiation, but chain growth is blocked by unexcised dimers. In both cell types recovery of the ability to synthesize normal-sized DNA was prevented by growing cells in caffeine after irradiation, possibly because of competition between the DNA binding properties of caffeine and replication proteins. Our observations imply that excision repair and semiconservative replication interact strongly in irradiated cells to produce a complex spectrum of changes in DNA replication which may be confused with parts of alternative systems such as post-replication repair."}
{"id": "PMID:220593", "title": "The effect of the superhelicity on the double helix twist angle in DNA.", "content": "An attempt to estimate the relative contributions of twisting and bending to the free energy of superhelix formation from the relaxed DNA is undertaken. The extent of teritiary ordering (number of DNA axis turns tau) and that of secondary ordering (duplex twist angle beta) have been taken as thermodynamical parameters, which characterize the state of the supercoild DNA at the fixed linking number (Lk) value. Such a thermodynamical approach implies the phenomenological parameters of rigidities of twisting and supercoiling (Gbeta, Gtau). Gtau/Gbeta ratio is estimated from the presented experimental data on the winding of the double helix upon increasing the ionic strength when twist alterations are followed by circular dichroism method. The adequacy of such interpretation of CD spectra changes are discussed. The values of Gtau and Gbeta are estimated to be of the same order of magnitude.", "contents": "The effect of the superhelicity on the double helix twist angle in DNA. An attempt to estimate the relative contributions of twisting and bending to the free energy of superhelix formation from the relaxed DNA is undertaken. The extent of teritiary ordering (number of DNA axis turns tau) and that of secondary ordering (duplex twist angle beta) have been taken as thermodynamical parameters, which characterize the state of the supercoild DNA at the fixed linking number (Lk) value. Such a thermodynamical approach implies the phenomenological parameters of rigidities of twisting and supercoiling (Gbeta, Gtau). Gtau/Gbeta ratio is estimated from the presented experimental data on the winding of the double helix upon increasing the ionic strength when twist alterations are followed by circular dichroism method. The adequacy of such interpretation of CD spectra changes are discussed. The values of Gtau and Gbeta are estimated to be of the same order of magnitude."}
{"id": "PMID:220597", "title": "RSV-induced tumors in chickens: resistance to pulsed current in terminal and non-terminal types.", "content": "Terminal Rous sarcoma virus-induced tumors in chickens had lower resistance to a pulsed current than non-terminal tumors or healthy tissues. This finding suggests the existence of some basic physiological difference between terminal and non-terminal tumors. The terminal tumors may have a higher concentration of mobile ions than either non-terminal types or healthy tissue.", "contents": "RSV-induced tumors in chickens: resistance to pulsed current in terminal and non-terminal types. Terminal Rous sarcoma virus-induced tumors in chickens had lower resistance to a pulsed current than non-terminal tumors or healthy tissues. This finding suggests the existence of some basic physiological difference between terminal and non-terminal tumors. The terminal tumors may have a higher concentration of mobile ions than either non-terminal types or healthy tissue."}
{"id": "PMID:220598", "title": "Effect of dietary energy on hepatic glycogen metabolism in the turkey hen.", "content": "An experiment was conducted with turkey hens to investigate the effect of substituting 30% of the carbohydrate calories with corn oil, 1,3-butanediol, or glycerol. Birds fed additional corn oil had the lowest liver glycogen concentration. Corn oil increased phosphorylase, a total phosphorylase, and glycogen synthetase I in comparison to the controls. Also, additional corn oil resulted in the highest specific activity of glucose-6-phosphatase. Dietary glycerol caused the highest concentration of liver glycogen. Glycerol increased glycogen synthetase I, but had little effect upon total activity in comparison to butanediol in the diet. Both butanediol and glycerol gave similar phosphorylase a activity, but butanediol increased total activity. The fat-fed and control-fed hens regulated hepatic glycogen concentration through phosphorylase, while glycerol and butanediol-fed hens regulated glycogen through glycogen synthetase. In vitro activation of glycogen synthetase I was deficient in hens fed additional corn oil, indicating a lack of glycogen synthetase phosphatase activity. The order of activation (glycerol greater than butanediol greater than control greater than corn oil) corresponds to the rank of glycogen concentrations", "contents": "Effect of dietary energy on hepatic glycogen metabolism in the turkey hen. An experiment was conducted with turkey hens to investigate the effect of substituting 30% of the carbohydrate calories with corn oil, 1,3-butanediol, or glycerol. Birds fed additional corn oil had the lowest liver glycogen concentration. Corn oil increased phosphorylase, a total phosphorylase, and glycogen synthetase I in comparison to the controls. Also, additional corn oil resulted in the highest specific activity of glucose-6-phosphatase. Dietary glycerol caused the highest concentration of liver glycogen. Glycerol increased glycogen synthetase I, but had little effect upon total activity in comparison to butanediol in the diet. Both butanediol and glycerol gave similar phosphorylase a activity, but butanediol increased total activity. The fat-fed and control-fed hens regulated hepatic glycogen concentration through phosphorylase, while glycerol and butanediol-fed hens regulated glycogen through glycogen synthetase. In vitro activation of glycogen synthetase I was deficient in hens fed additional corn oil, indicating a lack of glycogen synthetase phosphatase activity. The order of activation (glycerol greater than butanediol greater than control greater than corn oil) corresponds to the rank of glycogen concentrations"}
{"id": "PMID:220600", "title": "Characterization of an inhibitor of hepatic cholesterogenesis present in hepatic microsomes.", "content": "An inhibitor of hepatic cholesterol synthesis present in hepatic microsomes can be solubilized either by an acetone or an ethanol powder preparation. Other methods such as methanol and chloroform:methanol powder preparations and treatment with EDTA do not solubilize the factor. The factor appears to be proteinaceous since its activity is lost after exposure to proteolytic enzymes and heat treatment. In addition, the inhibitor does not require a phospholipid for activity. 3this inhibitor is stable for long periods (60 hrs.) at room temperature and can be isolated in good yield from liver maintained at 4 degrees C for 8 hours postmortem.", "contents": "Characterization of an inhibitor of hepatic cholesterogenesis present in hepatic microsomes. An inhibitor of hepatic cholesterol synthesis present in hepatic microsomes can be solubilized either by an acetone or an ethanol powder preparation. Other methods such as methanol and chloroform:methanol powder preparations and treatment with EDTA do not solubilize the factor. The factor appears to be proteinaceous since its activity is lost after exposure to proteolytic enzymes and heat treatment. In addition, the inhibitor does not require a phospholipid for activity. 3this inhibitor is stable for long periods (60 hrs.) at room temperature and can be isolated in good yield from liver maintained at 4 degrees C for 8 hours postmortem."}
{"id": "PMID:220601", "title": "Large scale, analytical method for isolating basal lateral plasma membranes from rat duodenum.", "content": "A procedure is described for obtaining large amounts of basal lateral plasma membranes from the rat duodenal epithelium. The yield is approximately 50%, and the purification factor is 18; preparations from 25 rats routinely contain 100 mg of protein. The procedure depends on mild homogenization with a nitrogen cavitation bomb, followed by removal of brush borders by sedimentation in a weak centrifugal field. Basal lateral membranes in the resulting supernatant are partially purified by differential centrifugation in a medium which approximates their equilibrium density, and then further purified by equilibrium density gradient centrifugation in a high capacity zonal rotor. Brush border membranes may be isolated from the 450 x g pellet. Since both brush border and basal lateral membranes may be isolated from the same homogenate, this preparative procedure is suitable for such analytical purposes as determinations of distribution of enzyme activities between the two surfaces of the epithelium. The large scale of the isolation procedure makes it an appropriate starting point for purification of specific basal lateral membrane components.", "contents": "Large scale, analytical method for isolating basal lateral plasma membranes from rat duodenum. A procedure is described for obtaining large amounts of basal lateral plasma membranes from the rat duodenal epithelium. The yield is approximately 50%, and the purification factor is 18; preparations from 25 rats routinely contain 100 mg of protein. The procedure depends on mild homogenization with a nitrogen cavitation bomb, followed by removal of brush borders by sedimentation in a weak centrifugal field. Basal lateral membranes in the resulting supernatant are partially purified by differential centrifugation in a medium which approximates their equilibrium density, and then further purified by equilibrium density gradient centrifugation in a high capacity zonal rotor. Brush border membranes may be isolated from the 450 x g pellet. Since both brush border and basal lateral membranes may be isolated from the same homogenate, this preparative procedure is suitable for such analytical purposes as determinations of distribution of enzyme activities between the two surfaces of the epithelium. The large scale of the isolation procedure makes it an appropriate starting point for purification of specific basal lateral membrane components."}
{"id": "PMID:220602", "title": "Production of Ficoll, Percoll, and albumin gradients by the freeze-thaw method.", "content": "Ficoll, sucrose, albumin, and Percoll, a modified colloidal silica centrifugation medium, all form density gradients upon freezing and thawing. The data suggest that any density gradient material will form gradients upon freezing and thawing, provided the material is stable to freezing.", "contents": "Production of Ficoll, Percoll, and albumin gradients by the freeze-thaw method. Ficoll, sucrose, albumin, and Percoll, a modified colloidal silica centrifugation medium, all form density gradients upon freezing and thawing. The data suggest that any density gradient material will form gradients upon freezing and thawing, provided the material is stable to freezing."}
{"id": "PMID:220603", "title": "Large-scale purification of Na,K-ATPase and its protein subunits from lamb kidney medulla.", "content": "Procedures are described for the large-scale isolation of purified Na,K-ATPase (EC 3.6.1.3) from frozen lamb kidney outer medulla and for the separation of its two protein subunits by hydroxyapatite chromatography in sodium dodecyl sulfate (SDS). The methods described permit the routine isolation of up to 800 mg of purified Na,K-ATPase in one week, which can subsequently be separated into 500 mg of mr = 95,000 catalytic subunit and 200 mg of glycoprotein with four SDS-hydroxyapatite column runs.", "contents": "Large-scale purification of Na,K-ATPase and its protein subunits from lamb kidney medulla. Procedures are described for the large-scale isolation of purified Na,K-ATPase (EC 3.6.1.3) from frozen lamb kidney outer medulla and for the separation of its two protein subunits by hydroxyapatite chromatography in sodium dodecyl sulfate (SDS). The methods described permit the routine isolation of up to 800 mg of purified Na,K-ATPase in one week, which can subsequently be separated into 500 mg of mr = 95,000 catalytic subunit and 200 mg of glycoprotein with four SDS-hydroxyapatite column runs."}
{"id": "PMID:220605", "title": "Circular dichroic evidence for a conformational change in a cytochrome b--c1 complex by uncoupling agents.", "content": "Circular dichroic spectra of the cytochrome b--c1 complex exhibit bilobe formation typical of exciton splitting in the presence of uncoupler. Bilobe formation occurs if both cytochrome c1 and cytochrome b are fully reduced. The fully oxidized and ascorbate-reduced complexes are not altered dichroically by uncouplers. The exciton splitting induced by uncoupler is consistent with heme--heme interaction: specifically, interaction between the two cytochromes b in the complex.", "contents": "Circular dichroic evidence for a conformational change in a cytochrome b--c1 complex by uncoupling agents. Circular dichroic spectra of the cytochrome b--c1 complex exhibit bilobe formation typical of exciton splitting in the presence of uncoupler. Bilobe formation occurs if both cytochrome c1 and cytochrome b are fully reduced. The fully oxidized and ascorbate-reduced complexes are not altered dichroically by uncouplers. The exciton splitting induced by uncoupler is consistent with heme--heme interaction: specifically, interaction between the two cytochromes b in the complex."}
{"id": "PMID:220604", "title": "Coupling between oxidation state and hydrogen bond conformation in heme proteins.", "content": "In all heme proteins for which crystal structures are available, the N(epsilon) of a histidyl residue is bonded to the heme iron and N(delta) is hydrogen bonded to a carbonyl oxygen of the peptide backbone. We investigate here the possibility that a change in oxidation state of the iron or a change in the geometry of this hydrogen bond might change the hydrogen bond strength in a functionally significant way. Dimerization energies obtained from ab initio molecular orbital calculations on the hydrogen-bonded dimer of imidazole and planar formamide are used to represent the strength of this hydrogen bond in heme proteins. The effect of a change in iron oxidation state is modeled by varying the positive charge on imidazole. The effect of a change in hydrogen bond geometry is studied by employing x-ray coordinates for reduced and oxidized cytochrome c, deoxy- and metmyoglobin, and deoxy- and methemoglobin. Our conclusions are that the strength of this hydrogen bond in heme proteins is sensitive to both the oxidation state of the iron atom and to geometry changes on the order of those obtained from the x-ray coordinates. We speculate that the changes in oxidation state may be functionally coupled with changes in hydrogen bond geometry and that this hydrogen bond represents a feasible pathway to link protein conformation with redox potential or reactivity of the iron atom.", "contents": "Coupling between oxidation state and hydrogen bond conformation in heme proteins. In all heme proteins for which crystal structures are available, the N(epsilon) of a histidyl residue is bonded to the heme iron and N(delta) is hydrogen bonded to a carbonyl oxygen of the peptide backbone. We investigate here the possibility that a change in oxidation state of the iron or a change in the geometry of this hydrogen bond might change the hydrogen bond strength in a functionally significant way. Dimerization energies obtained from ab initio molecular orbital calculations on the hydrogen-bonded dimer of imidazole and planar formamide are used to represent the strength of this hydrogen bond in heme proteins. The effect of a change in iron oxidation state is modeled by varying the positive charge on imidazole. The effect of a change in hydrogen bond geometry is studied by employing x-ray coordinates for reduced and oxidized cytochrome c, deoxy- and metmyoglobin, and deoxy- and methemoglobin. Our conclusions are that the strength of this hydrogen bond in heme proteins is sensitive to both the oxidation state of the iron atom and to geometry changes on the order of those obtained from the x-ray coordinates. We speculate that the changes in oxidation state may be functionally coupled with changes in hydrogen bond geometry and that this hydrogen bond represents a feasible pathway to link protein conformation with redox potential or reactivity of the iron atom."}
{"id": "PMID:220606", "title": "Control of eIF-2 phosphatase activity in rabbit reticulocyte lysate.", "content": "A sensitive assay requiring picomole amounts of [32P]eIF-2 to measure eIF-2 phosphatase activity has been developed. Dephosphorylation of [32P]eIF-2 alpha (38,000-dalton subunit) is extremely rapid (t 1/2 = 20 sec) and occurs at the same rate in both hemin-supplemented and hemin-depleted lysates. In contrast, [32P]eIF-2 beta phosphate is stable under all conditions studied. At concentrations required to produce a transient inhibition of protein synthesis, GDP prevents dephosphorylation of half of the phosphate introduced on eIF-2 alpha by the hemin-controlled repressor. Equimolar GTP is without effect. The concept that the energy charge of the guanylate pool may regulate accessibility of a phosphorylated site on eIF-2 alpha to its phosphatase and the implication of this to the mechanism of hemin-regulated translational control are discussed.", "contents": "Control of eIF-2 phosphatase activity in rabbit reticulocyte lysate. A sensitive assay requiring picomole amounts of [32P]eIF-2 to measure eIF-2 phosphatase activity has been developed. Dephosphorylation of [32P]eIF-2 alpha (38,000-dalton subunit) is extremely rapid (t 1/2 = 20 sec) and occurs at the same rate in both hemin-supplemented and hemin-depleted lysates. In contrast, [32P]eIF-2 beta phosphate is stable under all conditions studied. At concentrations required to produce a transient inhibition of protein synthesis, GDP prevents dephosphorylation of half of the phosphate introduced on eIF-2 alpha by the hemin-controlled repressor. Equimolar GTP is without effect. The concept that the energy charge of the guanylate pool may regulate accessibility of a phosphorylated site on eIF-2 alpha to its phosphatase and the implication of this to the mechanism of hemin-regulated translational control are discussed."}
{"id": "PMID:220607", "title": "Adenylate cyclase and acetylcholine release regulated by separate serotonin receptors of somatic cell hybrids.", "content": "Serotonin activates adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] of NCB-20 neuroblastoma--brain hybrid cells with an activation constant of 530 nM, but has little or no effect on cellular cyclic AMP or cyclic GMP content of NIE-115 neuroblastoma or NG108-15 hybrid cells. In homogenates of NCB-20 hybrid cells, lysergic acid diethylamide stimulates adenylate cyclase activity (Kact = 12 nM) and partially inhibits (Ki = 10 nM) the stimulation of adenylate cyclase activity by serotonin. No desensitization was detected of serotonin receptors coupled to adenylate cyclase. Serotonin also depolarizes NCB-20, NG108-15, and NIE-115 cells and increases acetylcholine release. Serotonin receptors mediating depolarizing responses desensitize rapidly and reversibly, and the depolarizing effects of serotonin are neither mimicked nor inhibited by lysergic acid diethylamide. These results indicate that (i) NCB-20 cells possess at least two species of serotonin receptors, which independently regulate cellular functions, (ii) activation of adenylate cyclase does not directly affect membrane potential or acetylcholine release, and (iii) serotonin-dependent cell depolarization does not affect cyclic AMP or cyclic GMP synthesis in the cell lines tested.", "contents": "Adenylate cyclase and acetylcholine release regulated by separate serotonin receptors of somatic cell hybrids. Serotonin activates adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] of NCB-20 neuroblastoma--brain hybrid cells with an activation constant of 530 nM, but has little or no effect on cellular cyclic AMP or cyclic GMP content of NIE-115 neuroblastoma or NG108-15 hybrid cells. In homogenates of NCB-20 hybrid cells, lysergic acid diethylamide stimulates adenylate cyclase activity (Kact = 12 nM) and partially inhibits (Ki = 10 nM) the stimulation of adenylate cyclase activity by serotonin. No desensitization was detected of serotonin receptors coupled to adenylate cyclase. Serotonin also depolarizes NCB-20, NG108-15, and NIE-115 cells and increases acetylcholine release. Serotonin receptors mediating depolarizing responses desensitize rapidly and reversibly, and the depolarizing effects of serotonin are neither mimicked nor inhibited by lysergic acid diethylamide. These results indicate that (i) NCB-20 cells possess at least two species of serotonin receptors, which independently regulate cellular functions, (ii) activation of adenylate cyclase does not directly affect membrane potential or acetylcholine release, and (iii) serotonin-dependent cell depolarization does not affect cyclic AMP or cyclic GMP synthesis in the cell lines tested."}
{"id": "PMID:220608", "title": "Transfer of glucagon receptor from liver membranes to a foreign adenylate cyclase by a membrane fusion procedure.", "content": "Previous work had demonstrated the coupling of a beta-adrenergic receptor on an erythrocyte with the adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] of a tissue culture cell when the two cells were fused by Sendai virus. The validity of this finding for animal tissues in general, for membrane preparations, and for peptide hormone receptors could hitherto not be assessed. Available fusion procedures worked efficiently only with certain intact cells from tissue culture and with erythrocytes. In the present work a membrane fusion method was developed that causes the transfer of the glucagon receptor from purified rat liver membranes to Friend erythroleukemia cells; even direct transfer to a membrane fraction prepared from Friend cells became feasible. It can therefore be concluded that a peptide hormone receptor in a normal tissue membrane has properties similar to those demonstrated for a beta-adrenergic receptor in an erythrocyte: it exists in the membrane as a dissociable independent unit that can readily couple with the adenylate cyclase of a foreign cell. The efficiency of the membrane fusion procedure is due to the combined action of polyethylene glycol, phospholipids, stearylamine, and ATP in a salt medium. The method promises to be applicable to membranes of various cells and tissues, and it can probably be used to analyze hormone receptors and adenylate cyclase systems in states of malfunction by transfer to their respective counterpart in a normal cell membrane. Studies in biochemical hybridization of membrane components need not be limited to hormone activation of adenylate cyclase. With the aid of the membrane fusion method, this approach could be applied to any dissociable multicomponent system in biological membranes.", "contents": "Transfer of glucagon receptor from liver membranes to a foreign adenylate cyclase by a membrane fusion procedure. Previous work had demonstrated the coupling of a beta-adrenergic receptor on an erythrocyte with the adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] of a tissue culture cell when the two cells were fused by Sendai virus. The validity of this finding for animal tissues in general, for membrane preparations, and for peptide hormone receptors could hitherto not be assessed. Available fusion procedures worked efficiently only with certain intact cells from tissue culture and with erythrocytes. In the present work a membrane fusion method was developed that causes the transfer of the glucagon receptor from purified rat liver membranes to Friend erythroleukemia cells; even direct transfer to a membrane fraction prepared from Friend cells became feasible. It can therefore be concluded that a peptide hormone receptor in a normal tissue membrane has properties similar to those demonstrated for a beta-adrenergic receptor in an erythrocyte: it exists in the membrane as a dissociable independent unit that can readily couple with the adenylate cyclase of a foreign cell. The efficiency of the membrane fusion procedure is due to the combined action of polyethylene glycol, phospholipids, stearylamine, and ATP in a salt medium. The method promises to be applicable to membranes of various cells and tissues, and it can probably be used to analyze hormone receptors and adenylate cyclase systems in states of malfunction by transfer to their respective counterpart in a normal cell membrane. Studies in biochemical hybridization of membrane components need not be limited to hormone activation of adenylate cyclase. With the aid of the membrane fusion method, this approach could be applied to any dissociable multicomponent system in biological membranes."}
{"id": "PMID:220609", "title": "BK virus DNA sequence: extent of homology with simian virus 40 DNA.", "content": "The primary nucleotide sequence of three regions of BK virus (BKV) variant (MM) DNA has been determined. The region between map positions 0.715 and 0.900 includes the initiation points and partial coding sequences of the putative VP2 and VP3 proteins of BKV(MM), the amino acid sequences of which show over 80% homology with those of VP2 and VP3 of simian virus 40. The sequence of a potential leader protein X, 66 amino acids long for BKV(MM) and 62 long for simian virus 40, is also deduced. The regions between 0.595 and 0.398 and 0.310 and 0.175 include the coding sequence for the entire small t antigen and most of the large T antigen of BKV(MM). The DNA sequence within these regions comprises over 50% of the complete BKV(MM) genome and shows a 70% sequence homology with the corresponding regions of simian virus 40 DNA. This high degree of homology is at variance with the reported homology values of 11--20% estimated by hybridization measurements of heteroduplex analyses. Possible explanations for the discrepancy are discussed.", "contents": "BK virus DNA sequence: extent of homology with simian virus 40 DNA. The primary nucleotide sequence of three regions of BK virus (BKV) variant (MM) DNA has been determined. The region between map positions 0.715 and 0.900 includes the initiation points and partial coding sequences of the putative VP2 and VP3 proteins of BKV(MM), the amino acid sequences of which show over 80% homology with those of VP2 and VP3 of simian virus 40. The sequence of a potential leader protein X, 66 amino acids long for BKV(MM) and 62 long for simian virus 40, is also deduced. The regions between 0.595 and 0.398 and 0.310 and 0.175 include the coding sequence for the entire small t antigen and most of the large T antigen of BKV(MM). The DNA sequence within these regions comprises over 50% of the complete BKV(MM) genome and shows a 70% sequence homology with the corresponding regions of simian virus 40 DNA. This high degree of homology is at variance with the reported homology values of 11--20% estimated by hybridization measurements of heteroduplex analyses. Possible explanations for the discrepancy are discussed."}
{"id": "PMID:220610", "title": "Preparation of a disulfide-linked dimer of human placental lactogen fragment 1--134 with immunologic and biologic activity.", "content": "In order to determine the chemical features of human placental lactogen (hPL) necessary for its biologic activity we prepared the following fragments from the plasmin-cleaved hormone: reduced and alkylated 1--134, reduced and alkylated 141--191, and a 1--134 dimer joined through the single cysteinyl residue at position 53. In a radioimmunoassay using antibodies against native hPL, the two reduced and alkylated fragments produced nonparallel displacement and had less than 1% of the activity of hPL. The ability of reduced and alkylated 1--134 to bind to mammary gland receptors was less than 5% of that of hPL; reduced and alkylated 141--191 showed no detectable activity in the same assay. The 1--134 dimer, in contrast, had 20% of the immunologic activity and 30% of the ability to bind to lactogenic receptors relative to the native hormone. In an in vitro bioassay the lactogenic activity of the 1--134 dimer was equivalent to that of the native hormone. The circular dichroic spectra of hPL, reduced and alkylated 1--134, and 1--134 dimer indicated that the dimer had regained much of the helical content of the native hormone. Antibodies produced to reduced and alkylated 1--134 did not significantly crossreact with either native hPL or 1--134 dimer. From these data we conclude that the information for the lactogenic activity of hPL is contained in the first 134 amino acid residues and that the proper conformation is necessary for its biologic expression.", "contents": "Preparation of a disulfide-linked dimer of human placental lactogen fragment 1--134 with immunologic and biologic activity. In order to determine the chemical features of human placental lactogen (hPL) necessary for its biologic activity we prepared the following fragments from the plasmin-cleaved hormone: reduced and alkylated 1--134, reduced and alkylated 141--191, and a 1--134 dimer joined through the single cysteinyl residue at position 53. In a radioimmunoassay using antibodies against native hPL, the two reduced and alkylated fragments produced nonparallel displacement and had less than 1% of the activity of hPL. The ability of reduced and alkylated 1--134 to bind to mammary gland receptors was less than 5% of that of hPL; reduced and alkylated 141--191 showed no detectable activity in the same assay. The 1--134 dimer, in contrast, had 20% of the immunologic activity and 30% of the ability to bind to lactogenic receptors relative to the native hormone. In an in vitro bioassay the lactogenic activity of the 1--134 dimer was equivalent to that of the native hormone. The circular dichroic spectra of hPL, reduced and alkylated 1--134, and 1--134 dimer indicated that the dimer had regained much of the helical content of the native hormone. Antibodies produced to reduced and alkylated 1--134 did not significantly crossreact with either native hPL or 1--134 dimer. From these data we conclude that the information for the lactogenic activity of hPL is contained in the first 134 amino acid residues and that the proper conformation is necessary for its biologic expression."}
{"id": "PMID:220611", "title": "Lateral translational diffusion of cytochrome c oxidase in the mitochondrial energy-transducing membrane.", "content": "The degree of freedom for lateral translational diffusion by cytochrome c oxidase and other integral proteins in the energy-transducing membrane of the mitochondrion was determined by combining the use of an immunoglobulin probe monospecific for the oxidase with thermotropic lipid phase transitions. Lateral mobility of the oxidase was monitored by observing the distribution of the immunoglobulin probe on the membrane surface by deep-etch electron microscopy and by observing the distribution of intramembrane particles (integral proteins) in the hydrophobic interior of the membrane by freeze-fracture electron microscopy. Incubation of the membrane with the immunoglobulin resulted in a time-dependent clustering of predominantly large intramembrane particles. Low temperature-induced lipid phase transitions resulted in the close packing of all intramembrane particles and cytochrome c oxidase by lateral exclusion from domains of gel-state bilayer lipid and was completely reversible. However, when cytochrome c oxidase was crosslinked through an immunoglobulin lattice prior to returning the membrane to above the lipid phase transition temperature, small intramembrane particles rerandomized while the large oxidase-related particles remained clustered. These observations reveal that cytochrome c oxidase can diffuse laterally in the energy-transducing membrane, either independently of all other integral proteins or in physical union with one or more other integral proteins. In addition, many other as yet unidentified smaller integral proteins can diffuse independently of the oxidase.", "contents": "Lateral translational diffusion of cytochrome c oxidase in the mitochondrial energy-transducing membrane. The degree of freedom for lateral translational diffusion by cytochrome c oxidase and other integral proteins in the energy-transducing membrane of the mitochondrion was determined by combining the use of an immunoglobulin probe monospecific for the oxidase with thermotropic lipid phase transitions. Lateral mobility of the oxidase was monitored by observing the distribution of the immunoglobulin probe on the membrane surface by deep-etch electron microscopy and by observing the distribution of intramembrane particles (integral proteins) in the hydrophobic interior of the membrane by freeze-fracture electron microscopy. Incubation of the membrane with the immunoglobulin resulted in a time-dependent clustering of predominantly large intramembrane particles. Low temperature-induced lipid phase transitions resulted in the close packing of all intramembrane particles and cytochrome c oxidase by lateral exclusion from domains of gel-state bilayer lipid and was completely reversible. However, when cytochrome c oxidase was crosslinked through an immunoglobulin lattice prior to returning the membrane to above the lipid phase transition temperature, small intramembrane particles rerandomized while the large oxidase-related particles remained clustered. These observations reveal that cytochrome c oxidase can diffuse laterally in the energy-transducing membrane, either independently of all other integral proteins or in physical union with one or more other integral proteins. In addition, many other as yet unidentified smaller integral proteins can diffuse independently of the oxidase."}
{"id": "PMID:220612", "title": "Reversion to methionine independence in simian virus 40-transformed human and malignant rat fibroblasts is associated with altered ploidy and altered properties of transformation.", "content": "Many transformed and malignant cells, unlike normal cells, do not grow when methionine in the growth medium is replaced by its immediate precursor homocysteine [Chello, P. & Bertino, J. (1973) Cancer Res. 33, 1898-1904 and Hoffman, R. & Erbe, R. (1976) Proc. Natl. Acad. Sci. USA 73, 1523-1527]. Rare cells from those populations revert to methionine independence [Hoffman, R., Jacobsen, S. & Erbe, R. (1978) Biochem. Biophys. Res. Commun. 82, 228-234]. We report here that methionine-independent revertants of both human fibroblasts transformed by simian virus 40 and malignant rat fibroblasts concomitantly revert for some of the properties associated with the transformed state. Of the 13 methionine-independent revertants described here, 5 showed increased anchorage dependence as reflected by reduced cloning efficiences in methylcellulose; 8 showed an increased serum requirement for optimal growth; 8 showed decreased cell density in medium containing high serum; and 3 altered their cell morphology significantly. Eight of the 13 have increased chromosome numbers. All lines tested contained immunologically identifiable tumor antigen of simian virus 40. Thus by selecting for methionine independence it is possible to select for heterogeneous transformation revertants, indicating further a relationship between altered methionine metabolism and oncogenic transformation. Therefore a positive metabolic method to select for transformation revertants has been developed, and its use has resulted in selection of human transformation revertants.", "contents": "Reversion to methionine independence in simian virus 40-transformed human and malignant rat fibroblasts is associated with altered ploidy and altered properties of transformation. Many transformed and malignant cells, unlike normal cells, do not grow when methionine in the growth medium is replaced by its immediate precursor homocysteine [Chello, P. & Bertino, J. (1973) Cancer Res. 33, 1898-1904 and Hoffman, R. & Erbe, R. (1976) Proc. Natl. Acad. Sci. USA 73, 1523-1527]. Rare cells from those populations revert to methionine independence [Hoffman, R., Jacobsen, S. & Erbe, R. (1978) Biochem. Biophys. Res. Commun. 82, 228-234]. We report here that methionine-independent revertants of both human fibroblasts transformed by simian virus 40 and malignant rat fibroblasts concomitantly revert for some of the properties associated with the transformed state. Of the 13 methionine-independent revertants described here, 5 showed increased anchorage dependence as reflected by reduced cloning efficiences in methylcellulose; 8 showed an increased serum requirement for optimal growth; 8 showed decreased cell density in medium containing high serum; and 3 altered their cell morphology significantly. Eight of the 13 have increased chromosome numbers. All lines tested contained immunologically identifiable tumor antigen of simian virus 40. Thus by selecting for methionine independence it is possible to select for heterogeneous transformation revertants, indicating further a relationship between altered methionine metabolism and oncogenic transformation. Therefore a positive metabolic method to select for transformation revertants has been developed, and its use has resulted in selection of human transformation revertants."}
{"id": "PMID:220613", "title": "Inducers of mammalian cell differentiation stimulate dome formation in a differentiated kidney epithelial cell line (MDCK).", "content": "Cell cultures of a differentiated kidney epithelial cell line, MDCK, spontaneously form fluid-filled domes or hemicysts composed of numbers of cells as a manifestation of specialized epithelial transport phenomena. Addition to MDCK cells of a broad spectrum of compounds that are known as potent inducers of mammalian cell differentiation in cell culture caused a striking increase in the frequency of dome formation. Polar compounds such as N,N-dimethylformamide, dimethyl sulfoxide, or hexamethylene bisacetamide stimulated increased dome formation 15--30 hr after addition. Induction of domes by these compounds was prevented either by inhibitors of protein synthesis or by ouabain, cytochalasin B, or vinblastine. Inhibition of DNA synthesis did not block chemical induction of domes. Other inducers were compounds of physiological occurrence such as n-butyrate or adenosine. Furthermore, a variety of conditions expected to elevate intracellular levels of cyclic AMP also stimulated dome formation. These findings suggest the hypothesis that domes are formed in cell culture by a form of cell differentiation that is under positive control by cyclic AMP.", "contents": "Inducers of mammalian cell differentiation stimulate dome formation in a differentiated kidney epithelial cell line (MDCK). Cell cultures of a differentiated kidney epithelial cell line, MDCK, spontaneously form fluid-filled domes or hemicysts composed of numbers of cells as a manifestation of specialized epithelial transport phenomena. Addition to MDCK cells of a broad spectrum of compounds that are known as potent inducers of mammalian cell differentiation in cell culture caused a striking increase in the frequency of dome formation. Polar compounds such as N,N-dimethylformamide, dimethyl sulfoxide, or hexamethylene bisacetamide stimulated increased dome formation 15--30 hr after addition. Induction of domes by these compounds was prevented either by inhibitors of protein synthesis or by ouabain, cytochalasin B, or vinblastine. Inhibition of DNA synthesis did not block chemical induction of domes. Other inducers were compounds of physiological occurrence such as n-butyrate or adenosine. Furthermore, a variety of conditions expected to elevate intracellular levels of cyclic AMP also stimulated dome formation. These findings suggest the hypothesis that domes are formed in cell culture by a form of cell differentiation that is under positive control by cyclic AMP."}
{"id": "PMID:220614", "title": "Molecular reorganization of lipid bilayers by complement: a possible mechanism for membranolysis.", "content": "The interaction between the membrane attack complex (MAC) of complement and flat lipid bilayers was investigated. Using spin-labeled derivatives of phospholipids and cholesterol and electron paramagnetic resonance spectroscopy, we measured the penetration of the MAC into bilayers and its influence on the order of bilayers. The MAC precursor components C5b--6, C7, C8, and C9 did not exert any measurable influence on lipid membranes. Functional C5b--7 was shown to interact strongly with the bilayer surface without deep penetration into the bilayer. Formation of C5b--8 and especially C5b--9 caused a marked change in the anisotropy of spectra from probes located within the hydrocarbon phase. The spectral changes are not caused by changes in probe rotation and, in the case of the cholesterol probes, are not due to direct probe--protein interactions. For these reasons we interpret the spectral changes to be the result of reorientation of ordered bilayer lipids effected by strong binding of phospholipids to MAC proteins.", "contents": "Molecular reorganization of lipid bilayers by complement: a possible mechanism for membranolysis. The interaction between the membrane attack complex (MAC) of complement and flat lipid bilayers was investigated. Using spin-labeled derivatives of phospholipids and cholesterol and electron paramagnetic resonance spectroscopy, we measured the penetration of the MAC into bilayers and its influence on the order of bilayers. The MAC precursor components C5b--6, C7, C8, and C9 did not exert any measurable influence on lipid membranes. Functional C5b--7 was shown to interact strongly with the bilayer surface without deep penetration into the bilayer. Formation of C5b--8 and especially C5b--9 caused a marked change in the anisotropy of spectra from probes located within the hydrocarbon phase. The spectral changes are not caused by changes in probe rotation and, in the case of the cholesterol probes, are not due to direct probe--protein interactions. For these reasons we interpret the spectral changes to be the result of reorientation of ordered bilayer lipids effected by strong binding of phospholipids to MAC proteins."}
{"id": "PMID:220615", "title": "Biosynthesis in vitro of immunoreactive 31,000-dalton corticotropin/beta-endorphin-like material by bovine hypothalamus.", "content": "Enzymatically dispersed bovine hypothalamic or cortical tissue was maintained in culture in the presence of (3)H-labeled amino acids. After such incubation, extracts of cells and of media contained (3)H-labeled products that were specifically bound by immobilized affinity-purified antisera to corticotropin (ACTH) and beta-endorphin. The majority of these products eluted in the void volume (V(0)) upon Sephadex G-50 gel filtration; minor (3)H-labeled products eluted in the regions of the ovine beta-lipotropin marker and in fractions having apparent molecular weights of approximately 12,000 and 3800. Sequential use of these immobilized antisera revealed that most of the V(0) material contained both ACTH and beta-endorphin antigenic determinants within the same molecule(s), whereas retarded material contained only one of the determinants. When this V(0) material was rerun on a Sephadex G-75 column, it coeluted with the 31-kilodalton precursor of both ACTH and beta-endorphin obtained from a bovine anterior pituitary extract. Thus, the high molecular weight immunoreactive ACTH/beta-endorphin-like (3)H-labeled product(s) derived from the hypothalamic culture is similar to the pituitary-derived precursor in containing the dual antigenic determinants and in its gel filtration characteristics. In contrast, the cortex-derived cell preparation was devoid of (3)H-labeled products specifically reactive with the antisera employed.", "contents": "Biosynthesis in vitro of immunoreactive 31,000-dalton corticotropin/beta-endorphin-like material by bovine hypothalamus. Enzymatically dispersed bovine hypothalamic or cortical tissue was maintained in culture in the presence of (3)H-labeled amino acids. After such incubation, extracts of cells and of media contained (3)H-labeled products that were specifically bound by immobilized affinity-purified antisera to corticotropin (ACTH) and beta-endorphin. The majority of these products eluted in the void volume (V(0)) upon Sephadex G-50 gel filtration; minor (3)H-labeled products eluted in the regions of the ovine beta-lipotropin marker and in fractions having apparent molecular weights of approximately 12,000 and 3800. Sequential use of these immobilized antisera revealed that most of the V(0) material contained both ACTH and beta-endorphin antigenic determinants within the same molecule(s), whereas retarded material contained only one of the determinants. When this V(0) material was rerun on a Sephadex G-75 column, it coeluted with the 31-kilodalton precursor of both ACTH and beta-endorphin obtained from a bovine anterior pituitary extract. Thus, the high molecular weight immunoreactive ACTH/beta-endorphin-like (3)H-labeled product(s) derived from the hypothalamic culture is similar to the pituitary-derived precursor in containing the dual antigenic determinants and in its gel filtration characteristics. In contrast, the cortex-derived cell preparation was devoid of (3)H-labeled products specifically reactive with the antisera employed."}
{"id": "PMID:220616", "title": "Depressed cyclic AMP levels in airways smooth muscle from asthmatic dogs.", "content": "We tested mongrel dogs by intradermal injection and tracheobronchial aerosol challenge with Ascaris suum antigen extract. All dogs were skin-test positive but could be segregated, on the basis of airways resistance measurements, into \"asthmatic\" (bronchoreactive) and \"nonasthmatic\" (nonbronchoreactive) groups. By using tracheal rings from these dogs, we measured the abilities of the beta-adrenergic agonist, isoproterenol, to relax tracheal smooth muscle contracted by methacholine and to cause cyclic AMP (cAMP) accumulation in the presence and absence of methacholine. The magnitude of relaxation induced by any concentration of isoproterenol was always less in the smooth muscle from \"asthmatic\" dogs. In the same tissues the concentrations of cAMP after in vitro equilibration, but prior to isoproterenol addition, were significantly less in the \"asthmatic\" than \"nonasthmatic\" samples. The accumulation of cAMP due to isoproterenol was similar in both groups for every dose of isoproterenol so that the initial difference between groups in cAMP concentration was maintained in an additive fashion over the entire dose-response curve. Total protein content of trachealis muscles from both groups of dogs was the same. We conclude that beta-adrenergically sensitive adenylate cyclase is not impaired in tracheal smooth muscle from \"asthmatic\" dogs; rather, the basal concentration of cAMP is depressed in \"asthmatic\" airway smooth muscle, and this difference is maintained throughout the isoproterenol dose-response curve. The depressed intracellular cAMP concentrations may be related to the decreased relaxation induced by isoproterenol in the \"asthmatic\" tracheal smooth muscle.", "contents": "Depressed cyclic AMP levels in airways smooth muscle from asthmatic dogs. We tested mongrel dogs by intradermal injection and tracheobronchial aerosol challenge with Ascaris suum antigen extract. All dogs were skin-test positive but could be segregated, on the basis of airways resistance measurements, into \"asthmatic\" (bronchoreactive) and \"nonasthmatic\" (nonbronchoreactive) groups. By using tracheal rings from these dogs, we measured the abilities of the beta-adrenergic agonist, isoproterenol, to relax tracheal smooth muscle contracted by methacholine and to cause cyclic AMP (cAMP) accumulation in the presence and absence of methacholine. The magnitude of relaxation induced by any concentration of isoproterenol was always less in the smooth muscle from \"asthmatic\" dogs. In the same tissues the concentrations of cAMP after in vitro equilibration, but prior to isoproterenol addition, were significantly less in the \"asthmatic\" than \"nonasthmatic\" samples. The accumulation of cAMP due to isoproterenol was similar in both groups for every dose of isoproterenol so that the initial difference between groups in cAMP concentration was maintained in an additive fashion over the entire dose-response curve. Total protein content of trachealis muscles from both groups of dogs was the same. We conclude that beta-adrenergically sensitive adenylate cyclase is not impaired in tracheal smooth muscle from \"asthmatic\" dogs; rather, the basal concentration of cAMP is depressed in \"asthmatic\" airway smooth muscle, and this difference is maintained throughout the isoproterenol dose-response curve. The depressed intracellular cAMP concentrations may be related to the decreased relaxation induced by isoproterenol in the \"asthmatic\" tracheal smooth muscle."}
{"id": "PMID:220617", "title": "Immunocytochemical localization of cyclic GMP: light and electron microscope evidence for involvement of neuroglia.", "content": "Guanosine 3',5'-cyclic monophosphate (cGMP) immunoreactivity in the rat's cerebellum was studied with light and electron microscopy by the indirect fluorescence method and the peroxidase-antiperoxidase method. Labeled cells included neuroglial cells in the cerebellar cortex, white matter, and deep nuclei; some stellate and basket cells in the cortex; and some large neurons in the deep nuclei. No evidence was found for sagittal microzonation in the cGMP distribution. In the labeled cells, cGMP immunoreactive sites were localized to surface membranes, organelles, and the cytoplasmic matrix. Specificity was indicated by the same pattern of labeling after treatment with cGMP immunoglobulin that had been adsorbed with adenosine 3',5'-cyclic monophosphate (cAMP) and by the failure to label after treatment with normal rabbit sera or with cGMP immunoglobulin that had been adsorbed with 1 mM cGMP. Cerebella treated with cAMP antisera, however, showed immunoreactivity in Purkinje cells, granule cells, and Golgi cells in addition to neuroglia in cortex and deep nuclei. Sequential norepinephrine and glutamate superfusions generally intensified cGMP immunoreactivity, not only in neuroglial cells but also in the background. Under these conditions some Purkinje cells and some granule cells were also labeled. Increased cGMP immunoreactivity was also obtained by treatment with harmaline, gamma-aminobutyric acid and aminooxyacetic acid, muscimol, gamma-aminobutyric acid, or apomorphine in order of decreasing effectiveness. Serotonin and colchicine produced no detectable increase of cGMP immunoreactivity above normal, and diazepam and sodium pentobarbital decreased it. In these experiments, diethyl ether was preferable to sodium pentobarbital for anesthesia on account of the depressive action of the latter on cGMP immunoreactivity. Thus, drugs that increase cerebellar activity enhance cGMP levels, whereas those that decrease cerebellar activity decrease cGMP levels. However, it is not clear whether these fluctuations in cGMP levels are a direct consequence of neurotransmitter function or are sequelae to other related events. The present study suggests that some neurons and many neuroglial cells are the major sites of cGMP in the cerebellum.", "contents": "Immunocytochemical localization of cyclic GMP: light and electron microscope evidence for involvement of neuroglia. Guanosine 3',5'-cyclic monophosphate (cGMP) immunoreactivity in the rat's cerebellum was studied with light and electron microscopy by the indirect fluorescence method and the peroxidase-antiperoxidase method. Labeled cells included neuroglial cells in the cerebellar cortex, white matter, and deep nuclei; some stellate and basket cells in the cortex; and some large neurons in the deep nuclei. No evidence was found for sagittal microzonation in the cGMP distribution. In the labeled cells, cGMP immunoreactive sites were localized to surface membranes, organelles, and the cytoplasmic matrix. Specificity was indicated by the same pattern of labeling after treatment with cGMP immunoglobulin that had been adsorbed with adenosine 3',5'-cyclic monophosphate (cAMP) and by the failure to label after treatment with normal rabbit sera or with cGMP immunoglobulin that had been adsorbed with 1 mM cGMP. Cerebella treated with cAMP antisera, however, showed immunoreactivity in Purkinje cells, granule cells, and Golgi cells in addition to neuroglia in cortex and deep nuclei. Sequential norepinephrine and glutamate superfusions generally intensified cGMP immunoreactivity, not only in neuroglial cells but also in the background. Under these conditions some Purkinje cells and some granule cells were also labeled. Increased cGMP immunoreactivity was also obtained by treatment with harmaline, gamma-aminobutyric acid and aminooxyacetic acid, muscimol, gamma-aminobutyric acid, or apomorphine in order of decreasing effectiveness. Serotonin and colchicine produced no detectable increase of cGMP immunoreactivity above normal, and diazepam and sodium pentobarbital decreased it. In these experiments, diethyl ether was preferable to sodium pentobarbital for anesthesia on account of the depressive action of the latter on cGMP immunoreactivity. Thus, drugs that increase cerebellar activity enhance cGMP levels, whereas those that decrease cerebellar activity decrease cGMP levels. However, it is not clear whether these fluctuations in cGMP levels are a direct consequence of neurotransmitter function or are sequelae to other related events. The present study suggests that some neurons and many neuroglial cells are the major sites of cGMP in the cerebellum."}
{"id": "PMID:220641", "title": "ACTH4-9 analog (ORG 2766) facilitates acquisition of an inhibitory avoidance response in rats.", "content": "These experiments examined the effects of an ACTH4-9 analog (ORG 2766) on an inhibitory avoidance response in rats. Graded doses of ORG 2766 were administered either 1 hr prior to training, immediately after training, or 1 hr prior to the retention test. The animals were tested 24 hr after training. A 5.0 mg/kg dose was administered prior to training significantly facilitated acquisition of the response. ORG 2766 did not significantly affect retention when administered after training or prior to the retention test. Since ORG 2766 only affected acquisition of the response, it is suggested that the drug acts by influencing sensory, motivationl or attentional variables rather than directly affecting memory consolidation or retrieval processes.", "contents": "ACTH4-9 analog (ORG 2766) facilitates acquisition of an inhibitory avoidance response in rats. These experiments examined the effects of an ACTH4-9 analog (ORG 2766) on an inhibitory avoidance response in rats. Graded doses of ORG 2766 were administered either 1 hr prior to training, immediately after training, or 1 hr prior to the retention test. The animals were tested 24 hr after training. A 5.0 mg/kg dose was administered prior to training significantly facilitated acquisition of the response. ORG 2766 did not significantly affect retention when administered after training or prior to the retention test. Since ORG 2766 only affected acquisition of the response, it is suggested that the drug acts by influencing sensory, motivationl or attentional variables rather than directly affecting memory consolidation or retrieval processes."}
{"id": "PMID:220644", "title": "Possible participation of glucocorticoid in elevation of 3',5'-cyclic AMP levels through inhibition of cyclic AMP phosphodiesterase.", "content": "Administration of prednisolone and cholate to rats elevated levels of cAMP (adenosine 3',5'-cyclic monophosphate) by 1.5- to 2.0-fold. Compounds such as prednisolone, hydrocortisone, cholate, and deoxycholate were found to be potent inhibitors of partially purified cAMP phosphodiesterase prepared from rat liver. Kinetic analysis showed that the prednisolone inhibition was noncompetitive with a Ki of 8.9 x 10(-4) M. These results suggest that in addition to increasing DNA-dependent RNA polymerase activity in vivo, a large application of glucocorticoid may incur elevation of intracellular cAMP levels.", "contents": "Possible participation of glucocorticoid in elevation of 3',5'-cyclic AMP levels through inhibition of cyclic AMP phosphodiesterase. Administration of prednisolone and cholate to rats elevated levels of cAMP (adenosine 3',5'-cyclic monophosphate) by 1.5- to 2.0-fold. Compounds such as prednisolone, hydrocortisone, cholate, and deoxycholate were found to be potent inhibitors of partially purified cAMP phosphodiesterase prepared from rat liver. Kinetic analysis showed that the prednisolone inhibition was noncompetitive with a Ki of 8.9 x 10(-4) M. These results suggest that in addition to increasing DNA-dependent RNA polymerase activity in vivo, a large application of glucocorticoid may incur elevation of intracellular cAMP levels."}
{"id": "PMID:220645", "title": "Neural control of heartbeat in the leech and in some other invertebrates.", "content": "The heartbeat of the leech Hirudo consists of the contractile rhythm of the circular muscles in the wall of a bilateral pair of celomic sinuses, the heart tubes, that run the length of the leech body. The constriction cycles of the segmental heart-tube sections are coordinated so that on one body side they constrict in a rear-to-front progression (peristalsis), while on the other side they constrict nearly in concert (nonperistalsis). Spontaneous right-left reciprocal transitions between peristaltic and nonperistaltic coordination modes occur every few dozen heartbeat cycles. The constriction of each segmental heart-tube section is controlled via excitatory synapses by a rhythmically active heart motor neuron, or HE cell, of which 17 bilateral pairs are iterated in segmental ganglia of the ventral nerve cord. The activity rhythm of the HE cell ensemble is in turn controlled via inhibitory synapses by a rhythmically active heart interneuron, the HN cell, of which seven bilateral pairs are iterated in the rostral segmental ganglia. The HN heart interneuron owes its activity rhythm to an endogenous polarization cycle, and the cycles of all members of the HN cell ensemble are locked into an appropriate phase relation thanks to their mutual interconnection via excitatory and inhibitory synaptic connections. The observed activity pattern and identified synaptic connections of HE cells and HN cells can account not only for the generation of the two bilaterally asymmetric heartbeat coordination modes but also for the right-left coordination mode transitions. In contrast to the heartbeat of Hirudo, the beat of the single-chambered heart of the lobsters Panulirus and Homarus is controlled by a set of nine rhythmically active neurons that make up the cardiac ganglion. Of these, five larger cells are heart motor neurons that innervate the heart muscle fibers via excitatory synapses. The remaining four smaller neurons of the cardiac ganglion are interneurons that provide excitatory input to each other and to the heart motor neurons. Although all the neurons of the cardiac ganglion appear capable of producing their own endogenous polarization rhythm, it is currently believed that one of the interneurons acts as a pacemaker for the whole ensemble of interneurons and motor neurons. The beat of the two-chambered heart of the marine snail Aplysia is generated by yet an entirely different mechanism. Here, the basic contractile rhythm of the heart is due to an endogenous polarization cycle of the heart muscle fibers. That myogenic rhythm is controlled and modulated by a set of cardiovascular motor neurons located in the abdominal ganglion, some of which make excitatory and others of which make inhibitory connections with the heart muscle fibers. The activity of these cardiovascular motor neurons is controlled by three types of heart interneurons via both inhibitory and excitatory connections. The interneurons are in turn interconnected in a manner that prevents the simultaneous activation of antagonistic cardiac motor acts...", "contents": "Neural control of heartbeat in the leech and in some other invertebrates. The heartbeat of the leech Hirudo consists of the contractile rhythm of the circular muscles in the wall of a bilateral pair of celomic sinuses, the heart tubes, that run the length of the leech body. The constriction cycles of the segmental heart-tube sections are coordinated so that on one body side they constrict in a rear-to-front progression (peristalsis), while on the other side they constrict nearly in concert (nonperistalsis). Spontaneous right-left reciprocal transitions between peristaltic and nonperistaltic coordination modes occur every few dozen heartbeat cycles. The constriction of each segmental heart-tube section is controlled via excitatory synapses by a rhythmically active heart motor neuron, or HE cell, of which 17 bilateral pairs are iterated in segmental ganglia of the ventral nerve cord. The activity rhythm of the HE cell ensemble is in turn controlled via inhibitory synapses by a rhythmically active heart interneuron, the HN cell, of which seven bilateral pairs are iterated in the rostral segmental ganglia. The HN heart interneuron owes its activity rhythm to an endogenous polarization cycle, and the cycles of all members of the HN cell ensemble are locked into an appropriate phase relation thanks to their mutual interconnection via excitatory and inhibitory synaptic connections. The observed activity pattern and identified synaptic connections of HE cells and HN cells can account not only for the generation of the two bilaterally asymmetric heartbeat coordination modes but also for the right-left coordination mode transitions. In contrast to the heartbeat of Hirudo, the beat of the single-chambered heart of the lobsters Panulirus and Homarus is controlled by a set of nine rhythmically active neurons that make up the cardiac ganglion. Of these, five larger cells are heart motor neurons that innervate the heart muscle fibers via excitatory synapses. The remaining four smaller neurons of the cardiac ganglion are interneurons that provide excitatory input to each other and to the heart motor neurons. Although all the neurons of the cardiac ganglion appear capable of producing their own endogenous polarization rhythm, it is currently believed that one of the interneurons acts as a pacemaker for the whole ensemble of interneurons and motor neurons. The beat of the two-chambered heart of the marine snail Aplysia is generated by yet an entirely different mechanism. Here, the basic contractile rhythm of the heart is due to an endogenous polarization cycle of the heart muscle fibers. That myogenic rhythm is controlled and modulated by a set of cardiovascular motor neurons located in the abdominal ganglion, some of which make excitatory and others of which make inhibitory connections with the heart muscle fibers. The activity of these cardiovascular motor neurons is controlled by three types of heart interneurons via both inhibitory and excitatory connections. The interneurons are in turn interconnected in a manner that prevents the simultaneous activation of antagonistic cardiac motor acts..."}
{"id": "PMID:220646", "title": "Functional adaptation to reduction in renal mass.", "content": "As the population of nephrons diminishes, while the dietary intake and/or endogenous production of water and solutes is unchanged, there is a proportional increase in the excretion of water and solute by individual residual nephrons. This adaptive change, which preserves zero net balance in the early phase of renal insufficiency, involves a reduction in the fractional reabsorption of substances derived from the initial glomerular ultrafiltrate and an increase in the rate of secretion of solutes that are extracted by tubular epithelial cells from peritubular blood. These compensatory changes are adequate to maintain electrolyte and water homeostasis until severe renal failure ensures (GFR less than 20% of normal). After a moderate reduction in nephron population there is no evidence that the factors that modulate ion transport are qualitatively different from those that regulate renal function in the intact subject, when the excretory load of solute is varied by changes in intake or endogenous production. In severe renal insufficiency, however, it seems likely that several factors, not present in the subject with intact renal function, also play an important role in modifying the excretion of water and electrolytes. For example, an osmotic diuresis in severe renal failure apparently decreases the tubular reabsorption of sodium and divalent cations and that of water. Moreover, elaboration of a partially identified \"natriuretic\" substance may participate in the regulation of electrolyte excretion in severe renal insufficiency. The appearance of these factors in severe renal insufficiency probably complements mechanisms that normally regulate the transfer of water and ions across tubular epithelium, since even after a marked reduction in GFR the urinary excretion of solutes and water changes proportionally with intake, although within narrower limits than exist in normal subjects. Studies in experimental animals and in man with acquired renal disease demonstrate the important role of other factors in compensatory adaptation, in addition to changes in tubular transport. The marked increases in glomerular filtration rate and nephron blood flow, which occur at least in some conditions, increase the absolute amount of water and solute delivered to the various nephron segments in ultrafiltrate and peritubular blood. Moreover, the expansion of extracellular fluid in severe renal failure inhibits tubular reabsorption of filtered water and solute in the same qualitative way that has been demonstrated in subjects with intact renal function. Quantitatively the response to acute volume expansion is exaggerated compared with control. Concomitant changes in renal hypertrophy and hyperplasia probably play an important role in functional adaptation. The apparent marked capacity for compensatory growth in all nephron segments and even in portions of tubular segments in parenchymal renal disease increases the area for transport by tubular epithelia in residual nephrons, as the overall number of nephrons diminishes...", "contents": "Functional adaptation to reduction in renal mass. As the population of nephrons diminishes, while the dietary intake and/or endogenous production of water and solutes is unchanged, there is a proportional increase in the excretion of water and solute by individual residual nephrons. This adaptive change, which preserves zero net balance in the early phase of renal insufficiency, involves a reduction in the fractional reabsorption of substances derived from the initial glomerular ultrafiltrate and an increase in the rate of secretion of solutes that are extracted by tubular epithelial cells from peritubular blood. These compensatory changes are adequate to maintain electrolyte and water homeostasis until severe renal failure ensures (GFR less than 20% of normal). After a moderate reduction in nephron population there is no evidence that the factors that modulate ion transport are qualitatively different from those that regulate renal function in the intact subject, when the excretory load of solute is varied by changes in intake or endogenous production. In severe renal insufficiency, however, it seems likely that several factors, not present in the subject with intact renal function, also play an important role in modifying the excretion of water and electrolytes. For example, an osmotic diuresis in severe renal failure apparently decreases the tubular reabsorption of sodium and divalent cations and that of water. Moreover, elaboration of a partially identified \"natriuretic\" substance may participate in the regulation of electrolyte excretion in severe renal insufficiency. The appearance of these factors in severe renal insufficiency probably complements mechanisms that normally regulate the transfer of water and ions across tubular epithelium, since even after a marked reduction in GFR the urinary excretion of solutes and water changes proportionally with intake, although within narrower limits than exist in normal subjects. Studies in experimental animals and in man with acquired renal disease demonstrate the important role of other factors in compensatory adaptation, in addition to changes in tubular transport. The marked increases in glomerular filtration rate and nephron blood flow, which occur at least in some conditions, increase the absolute amount of water and solute delivered to the various nephron segments in ultrafiltrate and peritubular blood. Moreover, the expansion of extracellular fluid in severe renal failure inhibits tubular reabsorption of filtered water and solute in the same qualitative way that has been demonstrated in subjects with intact renal function. Quantitatively the response to acute volume expansion is exaggerated compared with control. Concomitant changes in renal hypertrophy and hyperplasia probably play an important role in functional adaptation. The apparent marked capacity for compensatory growth in all nephron segments and even in portions of tubular segments in parenchymal renal disease increases the area for transport by tubular epithelia in residual nephrons, as the overall number of nephrons diminishes..."}
{"id": "PMID:220649", "title": "Specific 3H-PGE1 binding sites in rat ovary in estrous cycle and pregnancy.", "content": "Stimulation of cAMP synthesis by prostaglandins E series in the rat ovary is consistent with the presence of a prostaglandin receptor in this tissue. Prostaglandin binding sites with specificity for PGE1 in vitro incubation systems have been demonstrated in rat ovary slices and corpora lutea. The binding of 3H-PGE1 was progressively inhibited with increasing amounts of unlabelled PGE1 and PGE2. PGF2alpha inhibitory effect was markedly smaller than that of PGE. 3H-PGE1 binding to the ovary was higher in 3-day-old rats than in 5-day-old and adult animals, when the highest binding was present in estrus. The specific binding of 3H-PGE1 to rat corpora lutea (CL) decreased on days 11 and 13 of pregnancy and then gradually returned to the level found on day 1 during the second half of gestation. This binding of labelled prostaglandin during pregnancy has been studied in relation to the PGE1 stimulation of cAMP synthesis in rat corpora lutea, but no consistent changes were observed in responsiveness.", "contents": "Specific 3H-PGE1 binding sites in rat ovary in estrous cycle and pregnancy. Stimulation of cAMP synthesis by prostaglandins E series in the rat ovary is consistent with the presence of a prostaglandin receptor in this tissue. Prostaglandin binding sites with specificity for PGE1 in vitro incubation systems have been demonstrated in rat ovary slices and corpora lutea. The binding of 3H-PGE1 was progressively inhibited with increasing amounts of unlabelled PGE1 and PGE2. PGF2alpha inhibitory effect was markedly smaller than that of PGE. 3H-PGE1 binding to the ovary was higher in 3-day-old rats than in 5-day-old and adult animals, when the highest binding was present in estrus. The specific binding of 3H-PGE1 to rat corpora lutea (CL) decreased on days 11 and 13 of pregnancy and then gradually returned to the level found on day 1 during the second half of gestation. This binding of labelled prostaglandin during pregnancy has been studied in relation to the PGE1 stimulation of cAMP synthesis in rat corpora lutea, but no consistent changes were observed in responsiveness."}
{"id": "PMID:220650", "title": "The stress induced increase of liver phosphorylase A and cyclic AMP in adrenomedullectomized and adrenalectomized rats.", "content": "In adult male rats injected with Pentobarbital, 50 mg.kg-1 i.p. and subjected immediately after administration of the anaesthetic to 400 revolutions (lasting of 6 min and 40 s) in rotating Noble-Collip drums the activity of the active form of hepatic phosphorylase was increased at time 0 after injury without respect to previous adrenomedullectomy or adrenalectomy (7 weeks or 10 days before, respectively). Completeness of surgery was checked by plasma catecholamines which were essentially near zero. The level of liver cAMP was increased in intact and adrenomedullectomized animals at time zero. 90 min after injury a recovery of enzyme activity towards basal levels was observed in contrast to cAMP which was increased in all the three groups. A net glycogenolytic response was found in the injured animals irrespective of previous surgery. It is concluded that for the stress induced activation of hepatic phosphorylase the presence of adrenal cortical and medullary tissue is not always indispensable.", "contents": "The stress induced increase of liver phosphorylase A and cyclic AMP in adrenomedullectomized and adrenalectomized rats. In adult male rats injected with Pentobarbital, 50 mg.kg-1 i.p. and subjected immediately after administration of the anaesthetic to 400 revolutions (lasting of 6 min and 40 s) in rotating Noble-Collip drums the activity of the active form of hepatic phosphorylase was increased at time 0 after injury without respect to previous adrenomedullectomy or adrenalectomy (7 weeks or 10 days before, respectively). Completeness of surgery was checked by plasma catecholamines which were essentially near zero. The level of liver cAMP was increased in intact and adrenomedullectomized animals at time zero. 90 min after injury a recovery of enzyme activity towards basal levels was observed in contrast to cAMP which was increased in all the three groups. A net glycogenolytic response was found in the injured animals irrespective of previous surgery. It is concluded that for the stress induced activation of hepatic phosphorylase the presence of adrenal cortical and medullary tissue is not always indispensable."}
{"id": "PMID:220652", "title": "A method of quantitating aggressive behaviour revealing possible dissociation of motor activity and aggression.", "content": "A method is described for quantitating isolation-induced aggression in wild male mice by measuring coarse motor activity. It is based on the operational definition that aggression is the form of motor activity in which two (or more) animals are involved in behaviour patterns, such as physical attack and/or defence including pursuit and flight. Both coarse and fine motor activity were measured by means of an electromagnetic activity meter. Four hundred ninety-two fights occurring among mice treated with various hormones, neurotransmitter antagonists, hashish, and cyproterone acetate were recorded; a positive significant correlation (P less than 0.001) between indices of fighting behaviour as well as fighting time and coarse motor activity were found. The simultaneous measurement of motor activity and aggression revealed dissociated effects of some drugs on non-aggressive fine motor activity and aggression.", "contents": "A method of quantitating aggressive behaviour revealing possible dissociation of motor activity and aggression. A method is described for quantitating isolation-induced aggression in wild male mice by measuring coarse motor activity. It is based on the operational definition that aggression is the form of motor activity in which two (or more) animals are involved in behaviour patterns, such as physical attack and/or defence including pursuit and flight. Both coarse and fine motor activity were measured by means of an electromagnetic activity meter. Four hundred ninety-two fights occurring among mice treated with various hormones, neurotransmitter antagonists, hashish, and cyproterone acetate were recorded; a positive significant correlation (P less than 0.001) between indices of fighting behaviour as well as fighting time and coarse motor activity were found. The simultaneous measurement of motor activity and aggression revealed dissociated effects of some drugs on non-aggressive fine motor activity and aggression."}
{"id": "PMID:220653", "title": "Long-term effect of ovariectomy on dopamine-stimulated adenylate cyclase in rat striatum and nucleus accumbens.", "content": "The long-term effects on dopamine-sensitive adenylate cyclase of deprivation of gonadal steroids resulting from ovariectomy were studied in extrahypothalamic areas of the brain, i.e. corpus striatum and nucleus accumbens. The results obtained show that in both central nervous system areas dopamine- and apomorphine-stimulated adenylate cyclase were significantly reduced, suggesting that the function of dopamine receptors in these areas was depressed.", "contents": "Long-term effect of ovariectomy on dopamine-stimulated adenylate cyclase in rat striatum and nucleus accumbens. The long-term effects on dopamine-sensitive adenylate cyclase of deprivation of gonadal steroids resulting from ovariectomy were studied in extrahypothalamic areas of the brain, i.e. corpus striatum and nucleus accumbens. The results obtained show that in both central nervous system areas dopamine- and apomorphine-stimulated adenylate cyclase were significantly reduced, suggesting that the function of dopamine receptors in these areas was depressed."}
{"id": "PMID:220654", "title": "Tardive dyskinesia: a clinical test of the supersensitivity hypothesis.", "content": "Patients with tardive dyskinesia showed no significant difference in CSF HVA when compared with groups of schizophrenic or depressives. CSF cAMP in the tardive dyskinesia group was significantly lower when compared to schizophrenics but not depressives. These results do not support a dopamine-receptor supersensitivity hypothesis in permanent tardive dyskinesia.", "contents": "Tardive dyskinesia: a clinical test of the supersensitivity hypothesis. Patients with tardive dyskinesia showed no significant difference in CSF HVA when compared with groups of schizophrenic or depressives. CSF cAMP in the tardive dyskinesia group was significantly lower when compared to schizophrenics but not depressives. These results do not support a dopamine-receptor supersensitivity hypothesis in permanent tardive dyskinesia."}
{"id": "PMID:220655", "title": "The effect of the combination of lithium and haloperidol on brain intermediary metabolism in vivo.", "content": "The effect of the chronic administration of the combination of lithium and haloperidol has been studied in rat brain in vivo. Lithium was administered in food in amounts sufficient to maintain serum lithium levels of 1.0 +/- 0.1 mEq/l; haloperidol (1.5 mg/kg) was given i.p. once daily. Control animals pair-fed with the lithium/haloperidol alone, or neither drug. Fifteen days after the beginning of the experiments the brains were instantaneously frozen with a rapid brain-freezing device and multiple metabolites were measured in the perchloric acid extract of the tissue. Intermediates examined included selected metabolites of the glycolytic pathway and the tricarboxylic acid cycle, N-acetylaspartate and cofactors such as ATP, CoA, and acetyl-CoA. Estimates of the effects of the treatments on cytoplasmic and mitochondrial redox states were also made. The results showed only minor effects of any of the treatments on any of the parameters studied and little or nothing to distinguish the combination of lithium and haloperidol from either treatment alone.", "contents": "The effect of the combination of lithium and haloperidol on brain intermediary metabolism in vivo. The effect of the chronic administration of the combination of lithium and haloperidol has been studied in rat brain in vivo. Lithium was administered in food in amounts sufficient to maintain serum lithium levels of 1.0 +/- 0.1 mEq/l; haloperidol (1.5 mg/kg) was given i.p. once daily. Control animals pair-fed with the lithium/haloperidol alone, or neither drug. Fifteen days after the beginning of the experiments the brains were instantaneously frozen with a rapid brain-freezing device and multiple metabolites were measured in the perchloric acid extract of the tissue. Intermediates examined included selected metabolites of the glycolytic pathway and the tricarboxylic acid cycle, N-acetylaspartate and cofactors such as ATP, CoA, and acetyl-CoA. Estimates of the effects of the treatments on cytoplasmic and mitochondrial redox states were also made. The results showed only minor effects of any of the treatments on any of the parameters studied and little or nothing to distinguish the combination of lithium and haloperidol from either treatment alone."}
{"id": "PMID:220656", "title": "ACTH 4-10 in the amelioration of neuropsychological symptomatology associated with senile organic brain syndrome.", "content": "Eighteen male and female volunteers over the age of sixty who exhibited mild senile organic brain syndrome were administered ACTH 4-10 (Org OI 63) (30 mg, s.c.) or saline in a 2 X 2 Latin square design. Subjects experienced a reduction in depression and confusion and an increase in vigor. This evidence of an increase in vigor was supported behaviorally by a delay in the onset of increased latency in reaction time. Data also indicated that retrieval from memory may be enhanced by this compound. The electroencephalogram evinced a shift to lower frequencies under ACTH 4-10, but this effect was primarily noted in the females who received drug followed by placebo. These effects of ACTH 4-10 are intriguing and suggest that further work in this area should be encouraged.", "contents": "ACTH 4-10 in the amelioration of neuropsychological symptomatology associated with senile organic brain syndrome. Eighteen male and female volunteers over the age of sixty who exhibited mild senile organic brain syndrome were administered ACTH 4-10 (Org OI 63) (30 mg, s.c.) or saline in a 2 X 2 Latin square design. Subjects experienced a reduction in depression and confusion and an increase in vigor. This evidence of an increase in vigor was supported behaviorally by a delay in the onset of increased latency in reaction time. Data also indicated that retrieval from memory may be enhanced by this compound. The electroencephalogram evinced a shift to lower frequencies under ACTH 4-10, but this effect was primarily noted in the females who received drug followed by placebo. These effects of ACTH 4-10 are intriguing and suggest that further work in this area should be encouraged."}
{"id": "PMID:220657", "title": "Cerebrospinal fluid cyclic AMP and acid monoamine metabolites following probenecid: studies in psychiatric patients.", "content": "At probenecid levels greater than 10 microgram/ml, CSF cAMP was independent of CSF probenecid concentration. At these levels of probenecid, cAMP transport out of CSF is probably maximally blocked and cAMP levels reflect cAMP release into CSF. CSF cAMP was significantly higher in RDC-diagnosed schizophrenics than in other psychotics or depressives. A significant decrease in CSF cAMP was found in psychotic patients treated with chlorpromazine, No changes in CSF cAMP were observed in patients treated with tricyclic antidepressants or lithium.", "contents": "Cerebrospinal fluid cyclic AMP and acid monoamine metabolites following probenecid: studies in psychiatric patients. At probenecid levels greater than 10 microgram/ml, CSF cAMP was independent of CSF probenecid concentration. At these levels of probenecid, cAMP transport out of CSF is probably maximally blocked and cAMP levels reflect cAMP release into CSF. CSF cAMP was significantly higher in RDC-diagnosed schizophrenics than in other psychotics or depressives. A significant decrease in CSF cAMP was found in psychotic patients treated with chlorpromazine, No changes in CSF cAMP were observed in patients treated with tricyclic antidepressants or lithium."}
{"id": "PMID:220658", "title": "Enhancement of central norepinephrine and 5-hydroxytryptamine transmission by tricyclic antidepressants. A comparison.", "content": "The relative abilities of 1--3 mg/kg of desipramine (DES), imipramine (IMIP), amitriptyline (AMI), and chlorimipramine (CI-IMIP) to enhance synaptic transmission mediated by either NE or 5-HT were determined by testing their effects directly on NE or 5-HT transmission to sympathetic preganglionic neurons in unanesthetized, spinal cats. Effects on NE transmission were assessed on intraspinal excitatory pathways which utilize NE as a transmitter. Effects on 5-HT transmission were assessed on 5-HT-mediated depression of spinal sympathetic reflexes produced by 30 mg/kg of 5-HTP. Both DES and IMIP markedly enhanced transmission through the intraspinal excitatory NE pathways whereas AMI and CI-IMIP depressed transmission. However, both AMI and CI-IMIP modestly enhanced transmission in cats depleted of central 5-HT by pretreatment with parachlorophenylalanine. The relative potencies of the four drugs on excitatory NE transmission were DES greater than IMIP greater than AMI greater than CI-IMIP. Each of the four drugs also enhanced the 5-HTP-induced depression of spinal sympathetic reflexes, but their relative potencies on 5-HT transmission were just the opposite to those found on NE transmission. Therefore, all four drugs enhanced transmission by both NE and 5-HT, but their relative selectivities for the two transmitters differed markedly and were complementary. In general, the results support those of previous studies based on less direct methods for assessing inhibition of amine reuptake by tricyclic antidepressants.", "contents": "Enhancement of central norepinephrine and 5-hydroxytryptamine transmission by tricyclic antidepressants. A comparison. The relative abilities of 1--3 mg/kg of desipramine (DES), imipramine (IMIP), amitriptyline (AMI), and chlorimipramine (CI-IMIP) to enhance synaptic transmission mediated by either NE or 5-HT were determined by testing their effects directly on NE or 5-HT transmission to sympathetic preganglionic neurons in unanesthetized, spinal cats. Effects on NE transmission were assessed on intraspinal excitatory pathways which utilize NE as a transmitter. Effects on 5-HT transmission were assessed on 5-HT-mediated depression of spinal sympathetic reflexes produced by 30 mg/kg of 5-HTP. Both DES and IMIP markedly enhanced transmission through the intraspinal excitatory NE pathways whereas AMI and CI-IMIP depressed transmission. However, both AMI and CI-IMIP modestly enhanced transmission in cats depleted of central 5-HT by pretreatment with parachlorophenylalanine. The relative potencies of the four drugs on excitatory NE transmission were DES greater than IMIP greater than AMI greater than CI-IMIP. Each of the four drugs also enhanced the 5-HTP-induced depression of spinal sympathetic reflexes, but their relative potencies on 5-HT transmission were just the opposite to those found on NE transmission. Therefore, all four drugs enhanced transmission by both NE and 5-HT, but their relative selectivities for the two transmitters differed markedly and were complementary. In general, the results support those of previous studies based on less direct methods for assessing inhibition of amine reuptake by tricyclic antidepressants."}
{"id": "PMID:220660", "title": "Studies of hypoparathyroidism and pseudohypoparathyroidism.", "content": "Twenty eight hypocalcaemic patients were studied, 14 with primary hypoparathyroidism, nine with pseudohypoparathyroidism and two with hypo-hyperparathyroidism, to characterized the essential features of these disorders. Like tetany, which was present in 12 of the patients, epilepsy was a common symptom, occurring in 13, seven of whom had received anticonvulsants for two to eight years before hypocalcaemia was detected. Differentiation between primary and pseudohypoparathyroidism could not be made with certainty on clinical grounds but confident distinction could be made by measurement of endogenous parathyroid hormone concentrations and by testing for renal resistance to exogenous parathyroid hormone. This was achieved by measurement of the plasma and, in some patients, the urinary cyclic AMP response to an intravenous injection of highly purified bovine parathyroid hormone. These investigations were also valuable in the assessment of the other three hypocalcaemic patients in whom a diagnosis of parathyroid dysfunction would otherwise have been made. In 10 of the patients synthetic 1 alpha-hydroxylated forms of vitamin D were used to establish and maintain normocalcaemia, though their use required careful monitoring.", "contents": "Studies of hypoparathyroidism and pseudohypoparathyroidism. Twenty eight hypocalcaemic patients were studied, 14 with primary hypoparathyroidism, nine with pseudohypoparathyroidism and two with hypo-hyperparathyroidism, to characterized the essential features of these disorders. Like tetany, which was present in 12 of the patients, epilepsy was a common symptom, occurring in 13, seven of whom had received anticonvulsants for two to eight years before hypocalcaemia was detected. Differentiation between primary and pseudohypoparathyroidism could not be made with certainty on clinical grounds but confident distinction could be made by measurement of endogenous parathyroid hormone concentrations and by testing for renal resistance to exogenous parathyroid hormone. This was achieved by measurement of the plasma and, in some patients, the urinary cyclic AMP response to an intravenous injection of highly purified bovine parathyroid hormone. These investigations were also valuable in the assessment of the other three hypocalcaemic patients in whom a diagnosis of parathyroid dysfunction would otherwise have been made. In 10 of the patients synthetic 1 alpha-hydroxylated forms of vitamin D were used to establish and maintain normocalcaemia, though their use required careful monitoring."}
{"id": "PMID:220661", "title": "[Alpha-lipoproteins and viral hepatitis (author's transl)].", "content": "The plasma levels of alpha-lipoproteins, triglycerides, cholesterol, bilirubin, ALT and AST were followed serially in a group of 10 patients with acute viral hepatitis. Hypertrygliceridaemia, low level of cholesterol and very low level of alpha band of the lipoproteins were found at the onset of the disease. Alpha-lipoprotein reappeared gradually during the course of the disease and was sensitive indices of improvement of liver function. A negative linear correlation was found between alpha-lipoprotein and total bilirubin and between alpha-lipoprotein and ALT.", "contents": "[Alpha-lipoproteins and viral hepatitis (author's transl)]. The plasma levels of alpha-lipoproteins, triglycerides, cholesterol, bilirubin, ALT and AST were followed serially in a group of 10 patients with acute viral hepatitis. Hypertrygliceridaemia, low level of cholesterol and very low level of alpha band of the lipoproteins were found at the onset of the disease. Alpha-lipoprotein reappeared gradually during the course of the disease and was sensitive indices of improvement of liver function. A negative linear correlation was found between alpha-lipoprotein and total bilirubin and between alpha-lipoprotein and ALT."}
{"id": "PMID:220668", "title": "Evaluation of angiography in Zollinger-Ellison syndrome.", "content": "Of 20 patients with the Zollinger-Ellison syndrome who underwent visceral angiography, only 3 had unequivocally positive studies for primary pancreatic tumors; another 5 patients had equivocal diagnoses based on adequate studies. Eight patients had no abnormalities of any kind detected by angiography (except for an obstructed splenic vein in one patient). Five patients were shown to have hypervascular liver metastases. These results contrast with most reports of findings in islet cell tumors in general and specifically with the findings in several small series of the Zollinger-Ellison syndrome.", "contents": "Evaluation of angiography in Zollinger-Ellison syndrome. Of 20 patients with the Zollinger-Ellison syndrome who underwent visceral angiography, only 3 had unequivocally positive studies for primary pancreatic tumors; another 5 patients had equivocal diagnoses based on adequate studies. Eight patients had no abnormalities of any kind detected by angiography (except for an obstructed splenic vein in one patient). Five patients were shown to have hypervascular liver metastases. These results contrast with most reports of findings in islet cell tumors in general and specifically with the findings in several small series of the Zollinger-Ellison syndrome."}
{"id": "PMID:220669", "title": "Ultrasound manifestations of hepatocellular carcinoma.", "content": "The ultrasound patterns of primary hepatocellular carcinoma are described. Three types were found: a densely echogenic mass, diffuse disease, and a mixture of the two. These three patterns correspond to the previously reported angiographic and pathological manifestations of disease. The differential diagnosis is discussed.", "contents": "Ultrasound manifestations of hepatocellular carcinoma. The ultrasound patterns of primary hepatocellular carcinoma are described. Three types were found: a densely echogenic mass, diffuse disease, and a mixture of the two. These three patterns correspond to the previously reported angiographic and pathological manifestations of disease. The differential diagnosis is discussed."}
{"id": "PMID:220670", "title": "Renal hyperconcentration of 99mTc-HEDP in experimental acute tubular necrosis.", "content": "The effect of transient renal ischemia on renal concentration and distribution of 99mTc-HEDP, 99mTc-DMSA, and 99mTc-DTPA was compared in rabbits with acute tubular necrosis. Scintigrams were obtained after injection in normal rabbits or ones with unilateral or bilateral ischemia. 99mTc-HEDP concentration in ischemic tissue was 8 to 18 times normal 1--4 hours after injection, and the resulting images delineated the morphological changes in the ischemic kidneys more accurately than those obtained with DMSA or DTPA. Calcium concentration in the ischemic kidneys increased sixfold. 99mTc-HEDP may be useful in evaluation of renal failure secondary to tubular injury.", "contents": "Renal hyperconcentration of 99mTc-HEDP in experimental acute tubular necrosis. The effect of transient renal ischemia on renal concentration and distribution of 99mTc-HEDP, 99mTc-DMSA, and 99mTc-DTPA was compared in rabbits with acute tubular necrosis. Scintigrams were obtained after injection in normal rabbits or ones with unilateral or bilateral ischemia. 99mTc-HEDP concentration in ischemic tissue was 8 to 18 times normal 1--4 hours after injection, and the resulting images delineated the morphological changes in the ischemic kidneys more accurately than those obtained with DMSA or DTPA. Calcium concentration in the ischemic kidneys increased sixfold. 99mTc-HEDP may be useful in evaluation of renal failure secondary to tubular injury."}
{"id": "PMID:220672", "title": "A comparison of the effects of PGI2, PGE2 and PGH2 on the cyclic nucleotide levels in rat anterior pituitary gland in vitro.", "content": "Rat anterior pituitary explants were incubated with PGI2, PGH2 and PGE2 in the presence of theophylline (1mM) and the production of cyclic AMP was measured. PGE2 was found to be about 20 times more potent than PGI2 while PGH2 was slightly more effective than PGI2. The results suggest that PGI2 does not play a AMP was measured. PGE was found to be about 20 times more potent than physiological role in cyclic AMP mediated events in the rat anterior pituitary.", "contents": "A comparison of the effects of PGI2, PGE2 and PGH2 on the cyclic nucleotide levels in rat anterior pituitary gland in vitro. Rat anterior pituitary explants were incubated with PGI2, PGH2 and PGE2 in the presence of theophylline (1mM) and the production of cyclic AMP was measured. PGE2 was found to be about 20 times more potent than PGI2 while PGH2 was slightly more effective than PGI2. The results suggest that PGI2 does not play a AMP was measured. PGE was found to be about 20 times more potent than physiological role in cyclic AMP mediated events in the rat anterior pituitary."}
{"id": "PMID:220673", "title": "Prostacyclin (PGI2) in pregnant human uterus.", "content": "Prostacyclin lowers the tonus and reduces the spontaneous motility of isolated pregnant human myometrium. This effect seems to be related to coclic-AMP accumulation, since PGI2 increases the formation of this cyclic nucleotide in incubated minces of pregnant and non-pregnant uterus. The ability of this tissue to generate a labile substance which inhibits platelets aggregation, has been demonstrated and discussed.", "contents": "Prostacyclin (PGI2) in pregnant human uterus. Prostacyclin lowers the tonus and reduces the spontaneous motility of isolated pregnant human myometrium. This effect seems to be related to coclic-AMP accumulation, since PGI2 increases the formation of this cyclic nucleotide in incubated minces of pregnant and non-pregnant uterus. The ability of this tissue to generate a labile substance which inhibits platelets aggregation, has been demonstrated and discussed."}
{"id": "PMID:220674", "title": "Pre-ovulatory changes in cyclic AMP and prostaglandin concentrations in follicular fluid of gilts.", "content": "The concentrations of cyclic adenosine 3', 5'-monophosphate (cyclic AMP) and prostaglandins E and F (PGE and PGF) were determined in follicular fluid collected from follicles of prepubertal gilts at various times after treatment with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) to induced ovulation. The concentrations of cyclic AMP, PGE and PGF in the follicular fluid after PMSG treatment but prior to hCG injection were about 1 pmol/ml, 1 ng/ml and 0.2 ng/ml, respectively. After hCG administration, the follicular fluid levels of cyclic AMP increased markedly, reaching a peak (400-fold increase) about 4 h after injection and then declined gradually to pre-hCG levels. A second rise (2.5- to 5-fold increase) occurred about 30 h after hCG with the levels being sustained up to the expected time of ovulation. In contrast, the levels of PGE and PGF remained relatively constant until 28-30 h after hCG treatment. Thereafter, the concentrations of both prostaglandins began to rise with the increases becoming more pronounced and reaching maximal values as the expected time of ovulation approached. These data provide further evidence for a physiological role of follicular prostaglandins in the process of ovulation but do not support an obligatory role for prostaglandins in the acute gonadotropin stimulation of cyclic AMP formation.", "contents": "Pre-ovulatory changes in cyclic AMP and prostaglandin concentrations in follicular fluid of gilts. The concentrations of cyclic adenosine 3', 5'-monophosphate (cyclic AMP) and prostaglandins E and F (PGE and PGF) were determined in follicular fluid collected from follicles of prepubertal gilts at various times after treatment with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) to induced ovulation. The concentrations of cyclic AMP, PGE and PGF in the follicular fluid after PMSG treatment but prior to hCG injection were about 1 pmol/ml, 1 ng/ml and 0.2 ng/ml, respectively. After hCG administration, the follicular fluid levels of cyclic AMP increased markedly, reaching a peak (400-fold increase) about 4 h after injection and then declined gradually to pre-hCG levels. A second rise (2.5- to 5-fold increase) occurred about 30 h after hCG with the levels being sustained up to the expected time of ovulation. In contrast, the levels of PGE and PGF remained relatively constant until 28-30 h after hCG treatment. Thereafter, the concentrations of both prostaglandins began to rise with the increases becoming more pronounced and reaching maximal values as the expected time of ovulation approached. These data provide further evidence for a physiological role of follicular prostaglandins in the process of ovulation but do not support an obligatory role for prostaglandins in the acute gonadotropin stimulation of cyclic AMP formation."}
{"id": "PMID:220675", "title": "Use of mini-columns packed with acid-washed Florisil for the rapid separation of A, E and F series prostaglandins.", "content": "A new procedure was developed for the rapid isolation of the A, E and F series prostaglandins from plasma extracts. This new procedure involves the use of mini-columns packed with acid-washed Florisil to rapidly separate the A, E and F series prostaglandins. These new mini-columns give flow rates of around 1 ml/min. and they generate a well-resolved chromatographic pattern while at the same time producing good recoveries for [3H]-labeled prostaglandins of the A, E and F series. Using these new mini-columns, large numbers of plasma extracts can be processed in a short period of time.", "contents": "Use of mini-columns packed with acid-washed Florisil for the rapid separation of A, E and F series prostaglandins. A new procedure was developed for the rapid isolation of the A, E and F series prostaglandins from plasma extracts. This new procedure involves the use of mini-columns packed with acid-washed Florisil to rapidly separate the A, E and F series prostaglandins. These new mini-columns give flow rates of around 1 ml/min. and they generate a well-resolved chromatographic pattern while at the same time producing good recoveries for [3H]-labeled prostaglandins of the A, E and F series. Using these new mini-columns, large numbers of plasma extracts can be processed in a short period of time."}
{"id": "PMID:220676", "title": "Actions of prostacyclin (PGI2) on adrenergic neuroeffector transmission in the rabbit kidney.", "content": "In the Tyrode's perfused rabbit kidney PGI2 (1.3 x 10(-8)-3.3 x 10(-7)M) dose-dependently inhibited vasoconstrictor responses to sympathetic nerve stimulation, as did PGE2. The dose-effect curve of the two compounds differed, making PGI2 the less potent in the low concentration and the more potent in the high. PGI2 also inhibited the vasoconstrictor response to exogenous noradrenaline, but it had no effect on transmitter release. The main metabolite of PGI2, 6-keto-PGF1 alpha, was ineffective both on noradrenaline release and on vascular responses to nerve stimulation or exogenous noradrenaline. It is suggested that PGI2, if a significant renal prostaglandin, may modulate renal neuroeffector transmission post-junctionally, thereby forming a complement to the prejunctional action of PGE2.", "contents": "Actions of prostacyclin (PGI2) on adrenergic neuroeffector transmission in the rabbit kidney. In the Tyrode's perfused rabbit kidney PGI2 (1.3 x 10(-8)-3.3 x 10(-7)M) dose-dependently inhibited vasoconstrictor responses to sympathetic nerve stimulation, as did PGE2. The dose-effect curve of the two compounds differed, making PGI2 the less potent in the low concentration and the more potent in the high. PGI2 also inhibited the vasoconstrictor response to exogenous noradrenaline, but it had no effect on transmitter release. The main metabolite of PGI2, 6-keto-PGF1 alpha, was ineffective both on noradrenaline release and on vascular responses to nerve stimulation or exogenous noradrenaline. It is suggested that PGI2, if a significant renal prostaglandin, may modulate renal neuroeffector transmission post-junctionally, thereby forming a complement to the prejunctional action of PGE2."}
{"id": "PMID:220678", "title": "[Study of distribution of 203Hg-chlormerodrin, 203Hg-nitrate and 99mTc-DMSA in kidney by macroautoradiography (author's transl)].", "content": "Serial macroautoradiograms were obtained to determine the distribution of 203Hg-chlormerodrin, 203Hg-nigrate and 99mTc-DMSA in kidney. In the study, normal rats were used and these three radiopharmaceuticals were injected intravenously. Initial images of 203Hg-chlormerodrin showed the accumulation in the outer cortex, but no significant radioactivity in the medullary. On the other hand, delayed images revealed radioactivity shifting in concentration from the outer cortex to the inner cortex. Distribution pattern of 203Hg-nitrate was similar to that of 203Hg-chlormerodrin. In contrast to 203Hg-chlormerodrin and 203Hg-nitrate, 99mTc-DMSA was retained in the outer cortex without temporal changes in the distribution.", "contents": "[Study of distribution of 203Hg-chlormerodrin, 203Hg-nitrate and 99mTc-DMSA in kidney by macroautoradiography (author's transl)]. Serial macroautoradiograms were obtained to determine the distribution of 203Hg-chlormerodrin, 203Hg-nigrate and 99mTc-DMSA in kidney. In the study, normal rats were used and these three radiopharmaceuticals were injected intravenously. Initial images of 203Hg-chlormerodrin showed the accumulation in the outer cortex, but no significant radioactivity in the medullary. On the other hand, delayed images revealed radioactivity shifting in concentration from the outer cortex to the inner cortex. Distribution pattern of 203Hg-nitrate was similar to that of 203Hg-chlormerodrin. In contrast to 203Hg-chlormerodrin and 203Hg-nitrate, 99mTc-DMSA was retained in the outer cortex without temporal changes in the distribution."}
{"id": "PMID:220679", "title": "[Immediate effects of thermal shocks on the plasma level of various components in the Rainbow trout: compounds indicating stress and protein fraction].", "content": "Rainbow trout were subjected to thermal shocks (9 degrees water temperature increase, 1 hr stay at 21 degrees and return to initial temperature) at the rate of 2 shocks a day during 1 day or 3 successive days. The observed changes only show a moderate reaction. cAMP does not vary; lactate slightly increases at 17 hr after the end of the shocks. Glucose seems to be the most reliable stress indicator; it increases at 2 hr and remains again above control value at 17 hr after a 3 day shock time. Fibrinogen increases after a 3 day shock time. Lastly, a strong decrease in low density lipoprotein level is seen at 17 hr following both shock duration times and from 2 hr in case of a 3 day shock time.", "contents": "[Immediate effects of thermal shocks on the plasma level of various components in the Rainbow trout: compounds indicating stress and protein fraction]. Rainbow trout were subjected to thermal shocks (9 degrees water temperature increase, 1 hr stay at 21 degrees and return to initial temperature) at the rate of 2 shocks a day during 1 day or 3 successive days. The observed changes only show a moderate reaction. cAMP does not vary; lactate slightly increases at 17 hr after the end of the shocks. Glucose seems to be the most reliable stress indicator; it increases at 2 hr and remains again above control value at 17 hr after a 3 day shock time. Fibrinogen increases after a 3 day shock time. Lastly, a strong decrease in low density lipoprotein level is seen at 17 hr following both shock duration times and from 2 hr in case of a 3 day shock time."}
{"id": "PMID:220684", "title": "[Effect of piribedil on nocturnal sleep (author's transl)].", "content": "Piribedil, a dopamine agonist, was administered to 5 normal male subjects for two weeks. During the first two nights there was a reduction of about 17 p. 100 in paradoxical sleep (PS) and an increase of about 13 p. 100 in slow sleep II. There was a 15 p. 100 increase in PS during the third night. This increase is maintained for 8 nights in 3 subjects and 13 nights in 2 subjects. Other sleep parameters were not altered. Piribedil appears to give the impression of satisfactory sleep by reducing the subjective period before falling asleep. Piribedil also diminishes the remembrance of dreams.", "contents": "[Effect of piribedil on nocturnal sleep (author's transl)]. Piribedil, a dopamine agonist, was administered to 5 normal male subjects for two weeks. During the first two nights there was a reduction of about 17 p. 100 in paradoxical sleep (PS) and an increase of about 13 p. 100 in slow sleep II. There was a 15 p. 100 increase in PS during the third night. This increase is maintained for 8 nights in 3 subjects and 13 nights in 2 subjects. Other sleep parameters were not altered. Piribedil appears to give the impression of satisfactory sleep by reducing the subjective period before falling asleep. Piribedil also diminishes the remembrance of dreams."}
{"id": "PMID:220688", "title": "Dual tracer single breath studies of gas transport in the lung.", "content": "We studied the ratio of the expired He and SF6 concentrations (He/SF6) after 1 litre inspirations of a gas mixture containing 5% of He and SF6. Five subjects aged 49 to 60 yrs. performed the maneuvers with both inspiration and expiration at 0.2--0.41/s or 1.5--2.01/s. In all subjects separation of the tracer gases was observed, the He/SF6 falling early to a minimum of 0.80 +/- 0.01 (mean +/- 1 SE), and increasing gradually during expiration to a maximum of 1.08 +/- 0.01. The slope of the SF6 alveolar plateau was 1.45 +/- 0.09 times that for He. Computer simulations of simultaneous convection and diffusion in an axisymmetrical series lung model predicted a pattern of He/SF6 early in expiration which corresponded qualitatively to that observed experimentally. However, the model did not predict a rising He/SF6 ratio late in expiration. This was simulated only by incorporation of parallel inhomogeneity with sequential emptying into the model analysis. Consideration of Taylor type dispersion and airway asymmetry did not influence the simulations significantly. The results suggest that differing slopes of the alveolar plateau of two tracer gases may be due to diffusion dependent concentration differences among lung units ventilated in parallel rather than due to stratification alone.", "contents": "Dual tracer single breath studies of gas transport in the lung. We studied the ratio of the expired He and SF6 concentrations (He/SF6) after 1 litre inspirations of a gas mixture containing 5% of He and SF6. Five subjects aged 49 to 60 yrs. performed the maneuvers with both inspiration and expiration at 0.2--0.41/s or 1.5--2.01/s. In all subjects separation of the tracer gases was observed, the He/SF6 falling early to a minimum of 0.80 +/- 0.01 (mean +/- 1 SE), and increasing gradually during expiration to a maximum of 1.08 +/- 0.01. The slope of the SF6 alveolar plateau was 1.45 +/- 0.09 times that for He. Computer simulations of simultaneous convection and diffusion in an axisymmetrical series lung model predicted a pattern of He/SF6 early in expiration which corresponded qualitatively to that observed experimentally. However, the model did not predict a rising He/SF6 ratio late in expiration. This was simulated only by incorporation of parallel inhomogeneity with sequential emptying into the model analysis. Consideration of Taylor type dispersion and airway asymmetry did not influence the simulations significantly. The results suggest that differing slopes of the alveolar plateau of two tracer gases may be due to diffusion dependent concentration differences among lung units ventilated in parallel rather than due to stratification alone."}
{"id": "PMID:220696", "title": "[Hypertrophic neuropathy with myotonia (author's transl)].", "content": "A case of distal amyotrophia is reported, in which there was associated isolated clinical and electrical myotonia. Nerve conduction rates were very reduced. The nerves showed rarefaction of nerve fibers with segmentary demyelinization and the formation of bulbar swellings. The signification of this observation is discussed, and it would not appear to be related to peripheral nerve lesions of the type sometimes seen in Steinert's disease or from an association of this affection with Charcot-Marie's disease. It would seem more reasonable to suggest the hypothesis of a particular type of association of a peroneal hypertrophic neuropathy and a myotonia similar to certain cases reported in the published literature.", "contents": "[Hypertrophic neuropathy with myotonia (author's transl)]. A case of distal amyotrophia is reported, in which there was associated isolated clinical and electrical myotonia. Nerve conduction rates were very reduced. The nerves showed rarefaction of nerve fibers with segmentary demyelinization and the formation of bulbar swellings. The signification of this observation is discussed, and it would not appear to be related to peripheral nerve lesions of the type sometimes seen in Steinert's disease or from an association of this affection with Charcot-Marie's disease. It would seem more reasonable to suggest the hypothesis of a particular type of association of a peroneal hypertrophic neuropathy and a myotonia similar to certain cases reported in the published literature."}
{"id": "PMID:220699", "title": "Immunopathological mechanisms in rheumatoid arthritis at the dual interface of the synovial membrane: the joint cavity and the pannus.", "content": "The significance of immune responses is examined in relation to clinicopathological changes in the rheumatoid joint and the concept of a dual site of action is developed. In the joint cavity interaction between immune complexes and complement is central to the phenomena observed, which depend on the generation of chemotactic factors and the ingress of polymorphs. Other chemical mediators--e.g. prostaglandins and lymphokines--are envisaged as playing a secondary or augmentory role. At the pannus-cartilage (and bone) junction the possibility is considered that changes are due to activation of a variety of cell types which results in enzymatic degradation of collagen in cartilage, osteolastic activity in bone and prostaglandin-induced depletion of bone. The production of migration inhibition factors by rheumatoid membranes is examined and some evidence in support of their lymphokine nature is found by gel filtration; their role as cell activators is considered.", "contents": "Immunopathological mechanisms in rheumatoid arthritis at the dual interface of the synovial membrane: the joint cavity and the pannus. The significance of immune responses is examined in relation to clinicopathological changes in the rheumatoid joint and the concept of a dual site of action is developed. In the joint cavity interaction between immune complexes and complement is central to the phenomena observed, which depend on the generation of chemotactic factors and the ingress of polymorphs. Other chemical mediators--e.g. prostaglandins and lymphokines--are envisaged as playing a secondary or augmentory role. At the pannus-cartilage (and bone) junction the possibility is considered that changes are due to activation of a variety of cell types which results in enzymatic degradation of collagen in cartilage, osteolastic activity in bone and prostaglandin-induced depletion of bone. The production of migration inhibition factors by rheumatoid membranes is examined and some evidence in support of their lymphokine nature is found by gel filtration; their role as cell activators is considered."}
{"id": "PMID:220701", "title": "A bile-acid-rich high-density lipoprotein (HDL) in acute hepatitis.", "content": "Severe liver dysfunction is often associated with alterations of plasma lipids and lipoproteins. In this study the high-density lipoprotein (HDL) class has been further investigated. HDL from patients with acute, cholestatic hepatitis (n = 10) was isolated and compared with that of normals. Lipid and protein analyses were performed during the acute stage of the disease, with consequent follow-up studies. It was found that (1) only apo A-I was decreased by 50% in the isolated HDL fractions, whereas apo A-II remained unchanged; apo A-I in total plasma was normal; (2) immunoelectrophoresis of hepatitis HDL against monospecific anti-A-II revealed one precipitin line but two or more bands against anti-A-I; (3) concomitant with an increase of phospholipids and a decrease of triglycerides and the total cholesterol fraction, hepatitis HDL contained 10--12 times more bile acid than normal HDL. Chenodeoxycholic acid was the predominant bile acid. These alterations were fully reversible when patients recovered. These parameters seem to be sensitive markers for the degree of disturbance and restoration of liver function. The structural-functional implications of the observed compositional changes of HDL during cholestasis are discussed.", "contents": "A bile-acid-rich high-density lipoprotein (HDL) in acute hepatitis. Severe liver dysfunction is often associated with alterations of plasma lipids and lipoproteins. In this study the high-density lipoprotein (HDL) class has been further investigated. HDL from patients with acute, cholestatic hepatitis (n = 10) was isolated and compared with that of normals. Lipid and protein analyses were performed during the acute stage of the disease, with consequent follow-up studies. It was found that (1) only apo A-I was decreased by 50% in the isolated HDL fractions, whereas apo A-II remained unchanged; apo A-I in total plasma was normal; (2) immunoelectrophoresis of hepatitis HDL against monospecific anti-A-II revealed one precipitin line but two or more bands against anti-A-I; (3) concomitant with an increase of phospholipids and a decrease of triglycerides and the total cholesterol fraction, hepatitis HDL contained 10--12 times more bile acid than normal HDL. Chenodeoxycholic acid was the predominant bile acid. These alterations were fully reversible when patients recovered. These parameters seem to be sensitive markers for the degree of disturbance and restoration of liver function. The structural-functional implications of the observed compositional changes of HDL during cholestasis are discussed."}
{"id": "PMID:220703", "title": "Metabolic and cardiovascular effects of salbutamol in atopic subjects with and without asthma.", "content": "An intravenous injection of 100 microgram salbutamol sulphate was administered to a group of atopic asthmatics and a group of atopic control subjects without asthma. There was no difference in the metabolic and cardiovascular reponses of the two groups.", "contents": "Metabolic and cardiovascular effects of salbutamol in atopic subjects with and without asthma. An intravenous injection of 100 microgram salbutamol sulphate was administered to a group of atopic asthmatics and a group of atopic control subjects without asthma. There was no difference in the metabolic and cardiovascular reponses of the two groups."}
{"id": "PMID:220704", "title": "Angiotensin-converting enzyme. I. Activity and correlation with serum lysozyme in sarcoidosis, other chest or lymph node diseases and healthy persons.", "content": "Serum angiotensin-converting enzyme (ACE) activity was studied in healthy controls, in 57 untreated sarcoidosis patients, and in 164 patients with other chest or lymph node diseases. The serum ACE activity of healthy persons was independent of sex, intake of meals, and smoking habits. There were no diurnal variations. Healthy children had a significantly higher ACE mean value than adults, whose ACE activity was not affected by age. The sarcoidosis patients had the highest ACE mean values, but those of patients with silicosis and asbestosis were also significantly elevated. Pulmonary cancer patients had decreased serum ACE activity, which was probably due to antimitotic treatment. Serum lysozyme (LZM) concentrations did not correlate with normal ACE activity, but the correlation between elevated ACE and LZM was significant in sarcoidosis and silicosis, and the trend was clearly the same for asbestosis. This indicates separate sources for these enzymes when ACE activity is normal, and a common source, i.e. macrophages, when ACE activity is increased. ACE production in certain diseases involving macrophages may be due to the bradykinin inhibiting effect of this enzyme.", "contents": "Angiotensin-converting enzyme. I. Activity and correlation with serum lysozyme in sarcoidosis, other chest or lymph node diseases and healthy persons. Serum angiotensin-converting enzyme (ACE) activity was studied in healthy controls, in 57 untreated sarcoidosis patients, and in 164 patients with other chest or lymph node diseases. The serum ACE activity of healthy persons was independent of sex, intake of meals, and smoking habits. There were no diurnal variations. Healthy children had a significantly higher ACE mean value than adults, whose ACE activity was not affected by age. The sarcoidosis patients had the highest ACE mean values, but those of patients with silicosis and asbestosis were also significantly elevated. Pulmonary cancer patients had decreased serum ACE activity, which was probably due to antimitotic treatment. Serum lysozyme (LZM) concentrations did not correlate with normal ACE activity, but the correlation between elevated ACE and LZM was significant in sarcoidosis and silicosis, and the trend was clearly the same for asbestosis. This indicates separate sources for these enzymes when ACE activity is normal, and a common source, i.e. macrophages, when ACE activity is increased. ACE production in certain diseases involving macrophages may be due to the bradykinin inhibiting effect of this enzyme."}
{"id": "PMID:220705", "title": "Angiotensin-converting enzyme. II. Serum activity in early and newly diagnosed sarcoidosis.", "content": "Serum angiotensin-converting enzyme (ACE) was studied in 51 patients with early or newly diagnosed sarcoidosis. Only 45% of these patients had increased ACE activity when their diagnosis was established, which diminishes the diagnostic value of this enzyme measurement. On the other hand, ACE accurately reflected disease activity, and it proved a useful tool for assessing of need for corticosteroid treatment. Patients with acute sarcoidosis associated with erythema nodosum (EN) had low ACE activity compared with the other patients with active, but less acute disease. Serum ACE was not significantly correlated with blood lymphocytes or the immunoglobulins, but there was a positive correlation between the enzyme and serum lysozyme, which strengthens the hypothesis of both enzymes being produced by the epithelioid cells of sarcoid granulomas.", "contents": "Angiotensin-converting enzyme. II. Serum activity in early and newly diagnosed sarcoidosis. Serum angiotensin-converting enzyme (ACE) was studied in 51 patients with early or newly diagnosed sarcoidosis. Only 45% of these patients had increased ACE activity when their diagnosis was established, which diminishes the diagnostic value of this enzyme measurement. On the other hand, ACE accurately reflected disease activity, and it proved a useful tool for assessing of need for corticosteroid treatment. Patients with acute sarcoidosis associated with erythema nodosum (EN) had low ACE activity compared with the other patients with active, but less acute disease. Serum ACE was not significantly correlated with blood lymphocytes or the immunoglobulins, but there was a positive correlation between the enzyme and serum lysozyme, which strengthens the hypothesis of both enzymes being produced by the epithelioid cells of sarcoid granulomas."}
{"id": "PMID:220706", "title": "Space-filling models of kinase clefts and conformation changes.", "content": "Space-filling models of yeast hexokinase, adenylate kinase, and phosphoglycerate kinase drawn by computer clearly portray the bilobal character of these phosphoryl transfer enzymes, and the deep cleft which is formed between the lobes. A dramatic conformational change occurs in hexokinase as glucose binds to the bottom of the cleft, which causes the two lobes of hexokinase to come together. A substrate-induced closing of the active site cleft is postulated to occur in other kinases as well. This change may provide a mechanism by which some of these enzymes reduce their inherent adenosine triphosphatase activity and could be a general requirement of the kinase reaction.", "contents": "Space-filling models of kinase clefts and conformation changes. Space-filling models of yeast hexokinase, adenylate kinase, and phosphoglycerate kinase drawn by computer clearly portray the bilobal character of these phosphoryl transfer enzymes, and the deep cleft which is formed between the lobes. A dramatic conformational change occurs in hexokinase as glucose binds to the bottom of the cleft, which causes the two lobes of hexokinase to come together. A substrate-induced closing of the active site cleft is postulated to occur in other kinases as well. This change may provide a mechanism by which some of these enzymes reduce their inherent adenosine triphosphatase activity and could be a general requirement of the kinase reaction."}
{"id": "PMID:220707", "title": "Beta-adrenergic-sensitive adenylate cyclase in secretory cells of choroid plexus.", "content": "Biochemical evidence supporting the sympathetic control of cerebrospinal fluid production has been obtained through identification of a specific beta-adrenergic-sensitive adenylate cyclase in the choroid plexus. The enzyme, which is localized in the secretory epithelium, is activated by low concentrations of isoproterenol and norepinephrine and appears separate from beta-adrenergic-sensitive adenylate cyclase present in cerebral blood vessels.", "contents": "Beta-adrenergic-sensitive adenylate cyclase in secretory cells of choroid plexus. Biochemical evidence supporting the sympathetic control of cerebrospinal fluid production has been obtained through identification of a specific beta-adrenergic-sensitive adenylate cyclase in the choroid plexus. The enzyme, which is localized in the secretory epithelium, is activated by low concentrations of isoproterenol and norepinephrine and appears separate from beta-adrenergic-sensitive adenylate cyclase present in cerebral blood vessels."}
{"id": "PMID:220708", "title": "Prolactin receptors in Rana catesbeiana during development and metamorphosis.", "content": "Specific binding of ovine prolactin was found in microsomal preparations of tail, gill, and kidney of the bullfrog Ran catesbeiana. Binding by larval and adult liver and by kidney before larval stage XVII was low or nondetectable. Renal binding increased during metamorphic climax and in response to treatment with thyroid hormone. The emergence of renal binding of prolactin may signify a shift in the hormone's participation in the control of hydromineral homeostasis from the gill, which is resorbed, to the kidney. A renal action of prolactin during climax may facilitate metamorphosis.", "contents": "Prolactin receptors in Rana catesbeiana during development and metamorphosis. Specific binding of ovine prolactin was found in microsomal preparations of tail, gill, and kidney of the bullfrog Ran catesbeiana. Binding by larval and adult liver and by kidney before larval stage XVII was low or nondetectable. Renal binding increased during metamorphic climax and in response to treatment with thyroid hormone. The emergence of renal binding of prolactin may signify a shift in the hormone's participation in the control of hydromineral homeostasis from the gill, which is resorbed, to the kidney. A renal action of prolactin during climax may facilitate metamorphosis."}
{"id": "PMID:220709", "title": "Testosterone reduces refractory period of stria terminalis neurons in the rat brain.", "content": "The absolute refractory period of neurons projecting from the corticomedial amygdala to the medial preoptic-anterior hypothalamic junction in rats was significantly increased by castration (from 1.01 to 1.61 milliseconds) and decreased again by testosterone (from 1.48 to 0.97 millisecond). Corticomedial amygdala neurons which projected to the capsule of the ventromedial nucleus of the hypothalamus were unaffected. These results demonstrate a specific, direct neuronal effect of testosterone.", "contents": "Testosterone reduces refractory period of stria terminalis neurons in the rat brain. The absolute refractory period of neurons projecting from the corticomedial amygdala to the medial preoptic-anterior hypothalamic junction in rats was significantly increased by castration (from 1.01 to 1.61 milliseconds) and decreased again by testosterone (from 1.48 to 0.97 millisecond). Corticomedial amygdala neurons which projected to the capsule of the ventromedial nucleus of the hypothalamus were unaffected. These results demonstrate a specific, direct neuronal effect of testosterone."}
{"id": "PMID:220711", "title": "[Hematological manifestations and complications in Sj\u00f6gren's syndrome (author's transl)].", "content": "The main hematological manifestations and complications seen in 18 cases of Sj\u00f6gren's syndrome are described: a slight anemia of the inflammatory type, a leucopenia, and/or an eosinophilia occur in about half of the patients. One case of auto-immune hemolytic anemia, one of pernicious anemia, 3 of hypoplastic anemia--one of them drug-induced--, and one of thrombocytopenic purpura have also occurred. The clinical and biological manifestations related to the disturbed immunologic status are also frequent: hyperglobulinemic purpura. Raynaud's syndrome due to cryoglobulinemia, rheumatoid factor, anti-nuclear factor. In 4 patients, the disease presented with or evolved into lymphadenopathy and/or splenomegaly; the initial \"pseudo-lymphoma\" diagnosis corresponded to different aspects or courses: in one cases, malignancy appeared soon, another has evolved in a chronic lympho-proliferative disease, a third one had the histologic features of angio-immunoblastic lymphadenopathy. These various manifestations, which may reveal the Sj\u00f6gren's syndrome, are discussed in the light of the litterature data.", "contents": "[Hematological manifestations and complications in Sj\u00f6gren's syndrome (author's transl)]. The main hematological manifestations and complications seen in 18 cases of Sj\u00f6gren's syndrome are described: a slight anemia of the inflammatory type, a leucopenia, and/or an eosinophilia occur in about half of the patients. One case of auto-immune hemolytic anemia, one of pernicious anemia, 3 of hypoplastic anemia--one of them drug-induced--, and one of thrombocytopenic purpura have also occurred. The clinical and biological manifestations related to the disturbed immunologic status are also frequent: hyperglobulinemic purpura. Raynaud's syndrome due to cryoglobulinemia, rheumatoid factor, anti-nuclear factor. In 4 patients, the disease presented with or evolved into lymphadenopathy and/or splenomegaly; the initial \"pseudo-lymphoma\" diagnosis corresponded to different aspects or courses: in one cases, malignancy appeared soon, another has evolved in a chronic lympho-proliferative disease, a third one had the histologic features of angio-immunoblastic lymphadenopathy. These various manifestations, which may reveal the Sj\u00f6gren's syndrome, are discussed in the light of the litterature data."}
{"id": "PMID:220712", "title": "[Diagnosis methods in Sj\u00f6gren's syndrome (author's transl)].", "content": "The diagnosis value of various methods used to detect or confirm a Sj\u00f6gren's syndrome are discussed. The Schirmer's test, generally abnormal, is a good test for detection, although not specific. A subnormal concentration of tears lysozyme is seen in about half of the patients, as so as the presence of anti-salivary ducts antibodies, or significant aspects in lip biopsy. The tests that are most frequently disturbed are the salivary immunoglobulin assay and the fonctionnal study of salivary glands with 99m technetium tracer but they are not specific. These abnormalities are neither constant, not specific: for this reason, there are frequently some problems in the diagnosis or the nosologic definition of Sj\u00f6gren's syndrome. The occurrence in the same subject of many of these abnormalities makes however this diagnosis highly probable even in patients without functionnal troubles.", "contents": "[Diagnosis methods in Sj\u00f6gren's syndrome (author's transl)]. The diagnosis value of various methods used to detect or confirm a Sj\u00f6gren's syndrome are discussed. The Schirmer's test, generally abnormal, is a good test for detection, although not specific. A subnormal concentration of tears lysozyme is seen in about half of the patients, as so as the presence of anti-salivary ducts antibodies, or significant aspects in lip biopsy. The tests that are most frequently disturbed are the salivary immunoglobulin assay and the fonctionnal study of salivary glands with 99m technetium tracer but they are not specific. These abnormalities are neither constant, not specific: for this reason, there are frequently some problems in the diagnosis or the nosologic definition of Sj\u00f6gren's syndrome. The occurrence in the same subject of many of these abnormalities makes however this diagnosis highly probable even in patients without functionnal troubles."}
{"id": "PMID:220713", "title": "[Systematic screening for Sj\u00f6gren's syndrome in patients with various blood diseases].", "content": "A Sj\u00f6gren's syndrom was looked for systematically in 154 hematological patients, half of them with lymphoproliferative disorders, by means of three current diagnosis methods: the Schirmer's test, the tear lysozyme assay, and the salivary immunoglobulin assay. These tests, poorly specific, are frequently abnormal, but the coexistence of the three abnormalities in the same patient makes the diagnosis highly probable. This corresponded to 4 patients. Taking into account the other diagnostic methods, the diagnosis was considered as possible or probable in 7 patients, and certain in 3 of them. This rate of 2% is discussed but the frequency of latent Sj\u00f6gren's syndrome in hematologic patients and mainly in lymphoproliferative disease cannot be considered as high.", "contents": "[Systematic screening for Sj\u00f6gren's syndrome in patients with various blood diseases]. A Sj\u00f6gren's syndrom was looked for systematically in 154 hematological patients, half of them with lymphoproliferative disorders, by means of three current diagnosis methods: the Schirmer's test, the tear lysozyme assay, and the salivary immunoglobulin assay. These tests, poorly specific, are frequently abnormal, but the coexistence of the three abnormalities in the same patient makes the diagnosis highly probable. This corresponded to 4 patients. Taking into account the other diagnostic methods, the diagnosis was considered as possible or probable in 7 patients, and certain in 3 of them. This rate of 2% is discussed but the frequency of latent Sj\u00f6gren's syndrome in hematologic patients and mainly in lymphoproliferative disease cannot be considered as high."}
{"id": "PMID:220714", "title": "[Pseudolymphoma and lymphoproliferative syndromes in Gougerot-Sj\u00f6gren syndrome (author's transl)].", "content": "Five cases of pseudolymphoma in Sj\u00f6gren's syndrome were reported. Pseudolymphoma's pathological aspects described by Rothman then Talal are discussed. After recognition of the Sj\u00f6gren's syndrome and a pseudolymphoma appearance, the risk of lymphomatous evolution enjoin a clinical close attention. Among our five cases, three had a peculiar evolution: one has presented and immunoblastic lymphoma (case 2). In an other case (case 3) the pathological aspect was very near to the angioimmunoblastic lymphadenopathy features. Waldenstr\u00f6m's macroglobulinemia was cause of death of the last one (case 5).", "contents": "[Pseudolymphoma and lymphoproliferative syndromes in Gougerot-Sj\u00f6gren syndrome (author's transl)]. Five cases of pseudolymphoma in Sj\u00f6gren's syndrome were reported. Pseudolymphoma's pathological aspects described by Rothman then Talal are discussed. After recognition of the Sj\u00f6gren's syndrome and a pseudolymphoma appearance, the risk of lymphomatous evolution enjoin a clinical close attention. Among our five cases, three had a peculiar evolution: one has presented and immunoblastic lymphoma (case 2). In an other case (case 3) the pathological aspect was very near to the angioimmunoblastic lymphadenopathy features. Waldenstr\u00f6m's macroglobulinemia was cause of death of the last one (case 5)."}
{"id": "PMID:220715", "title": "[Pernicious anaemia associated with Hashimoto's thyroiditis, Sj\u00f6gren's syndrome and chondrocalcinosis (author's transl)].", "content": "An association of pernicious anaemia. Hashimoto's thyroiditis, Sj\u00f6gren's syndrome and chondrocalcinosis in a 68 years old women is described. Such an observation, does not seem to have been reported previously; the frequency of the different associations and the specificity of the antibodies observed in each cases are discussed.", "contents": "[Pernicious anaemia associated with Hashimoto's thyroiditis, Sj\u00f6gren's syndrome and chondrocalcinosis (author's transl)]. An association of pernicious anaemia. Hashimoto's thyroiditis, Sj\u00f6gren's syndrome and chondrocalcinosis in a 68 years old women is described. Such an observation, does not seem to have been reported previously; the frequency of the different associations and the specificity of the antibodies observed in each cases are discussed."}
{"id": "PMID:220716", "title": "[The use of tobramycin in severe infections (author's transl)].", "content": "The interest of tobramycin, studied here in 63 cases of severe infection, is due to several factors: --its ease of use including in cases of renal insufficiency; --the efficiency of subcutaneous administration, of particular interest to patients on anticoagulants; --its action on multi-resistant Enterobacteria and those not responding to gentamicin. Antibiotherapy is however only one of the elements of success in the treatment of severe infections, beside two factors which are often linked and determining: early treatment and the development of foci resistant to antibiotics.", "contents": "[The use of tobramycin in severe infections (author's transl)]. The interest of tobramycin, studied here in 63 cases of severe infection, is due to several factors: --its ease of use including in cases of renal insufficiency; --the efficiency of subcutaneous administration, of particular interest to patients on anticoagulants; --its action on multi-resistant Enterobacteria and those not responding to gentamicin. Antibiotherapy is however only one of the elements of success in the treatment of severe infections, beside two factors which are often linked and determining: early treatment and the development of foci resistant to antibiotics."}
{"id": "PMID:220717", "title": "[Attacks of acute headache (author's transl)].", "content": "Acute headaches are in most cases significant symptoms or premonitary signs of a neurological condition. From a semiological point of view, they may be: (i) isolated, (ii) associated with neurological symptoms (ophtalmoplegia, hemiplegia, hemianesthesia...). From an etiological point of view, the haemorragic conditions are predominant (30%): encephalic vascular malformation with or without subarachnoidal haemorragia (21%), subarachnoidal haemorragia without malformation (6%) and subdural haematoma (3%). Two types of conditions are also frequently observed: ischemic attacks (22,3%) and inflammatory meningeal syndromes (12%). Rare cases with hypophyseal adenomas, ischemic attacks under oestro-progestative treatment, accidents of mono-amine-oxydase inhibitors and multiple sclerosis are observed. 23,8% of the cases remained without any precise diagnosis. One of the interesting points in the acute headache issue is the possibility of discovering an encephalic vascular malformation without any important bleeding and, therefore, good conditions for surgery.", "contents": "[Attacks of acute headache (author's transl)]. Acute headaches are in most cases significant symptoms or premonitary signs of a neurological condition. From a semiological point of view, they may be: (i) isolated, (ii) associated with neurological symptoms (ophtalmoplegia, hemiplegia, hemianesthesia...). From an etiological point of view, the haemorragic conditions are predominant (30%): encephalic vascular malformation with or without subarachnoidal haemorragia (21%), subarachnoidal haemorragia without malformation (6%) and subdural haematoma (3%). Two types of conditions are also frequently observed: ischemic attacks (22,3%) and inflammatory meningeal syndromes (12%). Rare cases with hypophyseal adenomas, ischemic attacks under oestro-progestative treatment, accidents of mono-amine-oxydase inhibitors and multiple sclerosis are observed. 23,8% of the cases remained without any precise diagnosis. One of the interesting points in the acute headache issue is the possibility of discovering an encephalic vascular malformation without any important bleeding and, therefore, good conditions for surgery."}
{"id": "PMID:220719", "title": "[Acquired idoxuridine resistance of herpes simplex virus. Clinical data (author's transl)].", "content": "The authors report two cases of severe herpetic keratitis and briefly discuss the possible mechanism of acquired idoxuridine resistance of herpes simplex virus. They believe that acquired resistance to IDU may be due to the treatment itself because of activity site of the inhibitor, i.e. the viral DNA.", "contents": "[Acquired idoxuridine resistance of herpes simplex virus. Clinical data (author's transl)]. The authors report two cases of severe herpetic keratitis and briefly discuss the possible mechanism of acquired idoxuridine resistance of herpes simplex virus. They believe that acquired resistance to IDU may be due to the treatment itself because of activity site of the inhibitor, i.e. the viral DNA."}
{"id": "PMID:220718", "title": "[Role of hormonal receptors in the regulation of the corpus luteum (author's transl)].", "content": "Recent publications dealing with the hormonal regulation of the corpus luteum function have been reviewed. Hormones involved in this regulation are: LH and placental analogue hCG, FSH, prolactin and placental analogue hPL, prostaglandins, oestradiol and androgens. The hormone receptor interaction in the luteal cells and the role of each hormone in the modulation of the cell responsiveness has been reviewed.", "contents": "[Role of hormonal receptors in the regulation of the corpus luteum (author's transl)]. Recent publications dealing with the hormonal regulation of the corpus luteum function have been reviewed. Hormones involved in this regulation are: LH and placental analogue hCG, FSH, prolactin and placental analogue hPL, prostaglandins, oestradiol and androgens. The hormone receptor interaction in the luteal cells and the role of each hormone in the modulation of the cell responsiveness has been reviewed."}
{"id": "PMID:220720", "title": "[Abrikossof tumor in the esophagus].", "content": "Among the benign tumours of the oesophagus, the discovery of an Abrikossof tumour is exceptional. Although modern methods of investigation now permit recognition of this tumour and suspect its benign nature, only histology permits one to determine its precise nature, either by biopsy or by frozen section. Histogenetically, the schwann cell and histiocytic theories are not completely incompatible to the extent that they are considered from the point of view of general pathology, where there is evidence in favour of the mesoectodermic origin of the granular cell myoblastomas. In all cases, surgical excision is necessary. This resection of the myoblastoma permits a permanent cure.", "contents": "[Abrikossof tumor in the esophagus]. Among the benign tumours of the oesophagus, the discovery of an Abrikossof tumour is exceptional. Although modern methods of investigation now permit recognition of this tumour and suspect its benign nature, only histology permits one to determine its precise nature, either by biopsy or by frozen section. Histogenetically, the schwann cell and histiocytic theories are not completely incompatible to the extent that they are considered from the point of view of general pathology, where there is evidence in favour of the mesoectodermic origin of the granular cell myoblastomas. In all cases, surgical excision is necessary. This resection of the myoblastoma permits a permanent cure."}
{"id": "PMID:220721", "title": "[Use of Celestene by ionization in the treatment of rheumatic diseases].", "content": "The authors report a series of 154 cases reports of 89 female and 65 men who were treated by dielectrolysis using a corticosteroid, bethamethasone phosphate (Celestene injectable). The ionization technique is recalled as: nature of the current, generator, electrodes, methods, as well as the protocol. Patients suffered mostly from rheumatologic diseases in particular scapulohumeral periarthritis, arthrosis, epicondylitis and abarticular syndromes, often long-standing and resistant to current therapeutics. This serie also comprises 15 Dupuytren's contractures and La Peyronie's diseases. The very favorable results state as good and very good in 82%. The authors emphasize the excellent tolerance of this therapeutic method which allows a profitable utilization of corticotherapy without any risk.", "contents": "[Use of Celestene by ionization in the treatment of rheumatic diseases]. The authors report a series of 154 cases reports of 89 female and 65 men who were treated by dielectrolysis using a corticosteroid, bethamethasone phosphate (Celestene injectable). The ionization technique is recalled as: nature of the current, generator, electrodes, methods, as well as the protocol. Patients suffered mostly from rheumatologic diseases in particular scapulohumeral periarthritis, arthrosis, epicondylitis and abarticular syndromes, often long-standing and resistant to current therapeutics. This serie also comprises 15 Dupuytren's contractures and La Peyronie's diseases. The very favorable results state as good and very good in 82%. The authors emphasize the excellent tolerance of this therapeutic method which allows a profitable utilization of corticotherapy without any risk."}
{"id": "PMID:220722", "title": "[Current research in therapy of postmenopausal osteoporosis (author's transl)].", "content": "The goals of osteoporosis treatment are not only to decrease bone resorption, but also and mainly to increase bone formation. Present research is based on bone histomorphometry and prospective double blind therapeutic studies. Physical exercise, adequate calcium intake oestrogen therapy in postmenopausal or oophorectomized women have been shown to be effective in prevention of the disease. A moderate beneficial effect of the association of synthetic anabolic steroids with oral calcium has been recognized. Better results are expected from combined treatments such as low doses of calcitonin and oral calcium, or vitamin D metabolites and sodium fluoride, and from stimulating bone formation by low doses of parat-hormone.", "contents": "[Current research in therapy of postmenopausal osteoporosis (author's transl)]. The goals of osteoporosis treatment are not only to decrease bone resorption, but also and mainly to increase bone formation. Present research is based on bone histomorphometry and prospective double blind therapeutic studies. Physical exercise, adequate calcium intake oestrogen therapy in postmenopausal or oophorectomized women have been shown to be effective in prevention of the disease. A moderate beneficial effect of the association of synthetic anabolic steroids with oral calcium has been recognized. Better results are expected from combined treatments such as low doses of calcitonin and oral calcium, or vitamin D metabolites and sodium fluoride, and from stimulating bone formation by low doses of parat-hormone."}
{"id": "PMID:220723", "title": "[Non cardiogenic pulmonary edema (author's transl)].", "content": "Non cardiogenic pulmonary edema is caused by an increase of alveolocapillary permeability, due to different etiologies: fat embolism, multiple trauma, septic shock, influenza pneumonia, aspiration syndrome... Chest radiographs exhibit interstitial and/or alveolar pattern, severity of injury is assessed by the magnitude of intra-pulmonary shunting. Pulmonary wedge pressure is normal, and increased pulmonary vascular resistance is sometimes evidence in prolonged evolutions, especially in fatal cases. Treatment consists in the suppression of hypervolemia, and ventilation with positive and expiratory pressure (PEEP). Extra-corporeal membrane lung oxygenation remains since now rather unsuccessful.", "contents": "[Non cardiogenic pulmonary edema (author's transl)]. Non cardiogenic pulmonary edema is caused by an increase of alveolocapillary permeability, due to different etiologies: fat embolism, multiple trauma, septic shock, influenza pneumonia, aspiration syndrome... Chest radiographs exhibit interstitial and/or alveolar pattern, severity of injury is assessed by the magnitude of intra-pulmonary shunting. Pulmonary wedge pressure is normal, and increased pulmonary vascular resistance is sometimes evidence in prolonged evolutions, especially in fatal cases. Treatment consists in the suppression of hypervolemia, and ventilation with positive and expiratory pressure (PEEP). Extra-corporeal membrane lung oxygenation remains since now rather unsuccessful."}
{"id": "PMID:220724", "title": "[Cardiogenic shock in acute myocardial infarction (author's transl)].", "content": "To date, pump failure and its extreme manifestation, cardiogenic shock are the most common cause of death in patients with acute myocardial infarction. Post-mortem studies have shown that primary (myocardial) cardiogenic shock does not occur until some 40 to 50% of the myocardium has been rendered nonfunctional. Not infrequently, cardiogenic shock is mainly the result of a mechanical lesion (mitral regurgitation secondary to papillary muscle dysfonction or rupture, or ventricular septal defect) superimposed upon an ischemic and infarcted ventricle. In both situations medical therapy usually produces only a limited effect. Numerous physiological studies have shown that balloon pumping can reduce the workload and oxygen demands of the heart while increasing coronary blood flow and cardiac output. Most patients with cardiogenic shock can be at least temporarily stabilized, but many patients are balloon-dependent in the sense that when circulatory support is temporarily discontinued, shock or severe heart failure recurs. In these patients, some attempt to correct the underlying anatomic abnormalities appears necessary if they are to survive. Early intra-aortic balloon pumping (IABP) and surgery is much more effective in patients with cardiogenic shock secondary to mechanical complications. Finally, the combination of IABP and surgery has resulted in survival of approximately 50% of patients with cardiogenic shock either primary or secondary.", "contents": "[Cardiogenic shock in acute myocardial infarction (author's transl)]. To date, pump failure and its extreme manifestation, cardiogenic shock are the most common cause of death in patients with acute myocardial infarction. Post-mortem studies have shown that primary (myocardial) cardiogenic shock does not occur until some 40 to 50% of the myocardium has been rendered nonfunctional. Not infrequently, cardiogenic shock is mainly the result of a mechanical lesion (mitral regurgitation secondary to papillary muscle dysfonction or rupture, or ventricular septal defect) superimposed upon an ischemic and infarcted ventricle. In both situations medical therapy usually produces only a limited effect. Numerous physiological studies have shown that balloon pumping can reduce the workload and oxygen demands of the heart while increasing coronary blood flow and cardiac output. Most patients with cardiogenic shock can be at least temporarily stabilized, but many patients are balloon-dependent in the sense that when circulatory support is temporarily discontinued, shock or severe heart failure recurs. In these patients, some attempt to correct the underlying anatomic abnormalities appears necessary if they are to survive. Early intra-aortic balloon pumping (IABP) and surgery is much more effective in patients with cardiogenic shock secondary to mechanical complications. Finally, the combination of IABP and surgery has resulted in survival of approximately 50% of patients with cardiogenic shock either primary or secondary."}
{"id": "PMID:220725", "title": "[Remission of diabetes during conventional insulin therapy or therapy controlled by use of an artificial pancreas].", "content": "12 recent acute-onset ketotic juvenile diabetics were optimally treated during 5 +/- days by means of an external artificial pancreas. Remission of diabetes occurred in 9 patients (75%). In a comparative group of 28 patients treated by conventional subcutaneous insulin, only 3 (11%) steady remissions were obtained. In a third group of 6 patients treated by insulin infusion without feed-back control, only 1 remission (17%) was obtained. The difference between these two groups and the first group (patients treated by the artificial pancreas) is significant (p less than 0.01). Urinary C-peptide/blood glucose ratio showed a steady improvement of insulin secretion during the remission period. At this time, actuarial analysis shows that the number of patients still in remission decreases during the first 10 months but seems to stabilize after this period. Duration of our remissions is equal to the duration of the \"spontaneous\" remissions taken from the literature. New treatment able to sustain the residual insulinsecretion during the remission phase (with presently can be induced frequently with our technique) are still to be found.", "contents": "[Remission of diabetes during conventional insulin therapy or therapy controlled by use of an artificial pancreas]. 12 recent acute-onset ketotic juvenile diabetics were optimally treated during 5 +/- days by means of an external artificial pancreas. Remission of diabetes occurred in 9 patients (75%). In a comparative group of 28 patients treated by conventional subcutaneous insulin, only 3 (11%) steady remissions were obtained. In a third group of 6 patients treated by insulin infusion without feed-back control, only 1 remission (17%) was obtained. The difference between these two groups and the first group (patients treated by the artificial pancreas) is significant (p less than 0.01). Urinary C-peptide/blood glucose ratio showed a steady improvement of insulin secretion during the remission period. At this time, actuarial analysis shows that the number of patients still in remission decreases during the first 10 months but seems to stabilize after this period. Duration of our remissions is equal to the duration of the \"spontaneous\" remissions taken from the literature. New treatment able to sustain the residual insulinsecretion during the remission phase (with presently can be induced frequently with our technique) are still to be found."}
{"id": "PMID:220726", "title": "[T-lymphocyte diseases. Physiopathological and nosologic concepts (excluding cancer and graft rejection)].", "content": "The T-lymphocyte is at the heart of the physiopathological mechanism of most dysimmunity affections. Furthermore, some cases of granulomatosis, the immediate consequence of macrophagic disorder, come within the framework of T-lymphocyte diseases, \u00e9picritical centre of the complex process of cellular immunity. By reference to new knowledges about various actions of T-lymphocytes and their interactions with lymphocytes B and macrophages, and by reference to classic pathologic findings of diseases of immunity, the author's propose a new classification of these diseases, suggesting therapeutic reasearch in consideration of effect of drugs, especially immunostimulant treatments, on the immune system.", "contents": "[T-lymphocyte diseases. Physiopathological and nosologic concepts (excluding cancer and graft rejection)]. The T-lymphocyte is at the heart of the physiopathological mechanism of most dysimmunity affections. Furthermore, some cases of granulomatosis, the immediate consequence of macrophagic disorder, come within the framework of T-lymphocyte diseases, \u00e9picritical centre of the complex process of cellular immunity. By reference to new knowledges about various actions of T-lymphocytes and their interactions with lymphocytes B and macrophages, and by reference to classic pathologic findings of diseases of immunity, the author's propose a new classification of these diseases, suggesting therapeutic reasearch in consideration of effect of drugs, especially immunostimulant treatments, on the immune system."}
{"id": "PMID:220727", "title": "[A clinical survey on 17 cases of cholelithiasis in childhood (author's transl)].", "content": "A series of 17 cases of gallstones in children observed over a period of 10 years in the area of Marseilles is described and the literature reviewed. The majority of children were girls over 10 years old. Symptoms were constantly present and the disease revealed nine times by acute \"mechanical\" cholecystitis, compared to 16 infectious cholecystitis followed during the same period, three times by an accident of migration (cholangitis in a 14 years old girl, bile ascitis in two infants). A cholecystography should be performed in acute recurrent abdominal pain of unknown origin in children, gallstones appearing to be radiotransparent in six patients. Among causes of gallstone formation, the authors dig out only 6 hemolytic anemias, related to hemoglobinopathies in three patients, and they emphasize the frequency of idiopathic cholelithiasis which should lead to a more complete investigation of the enterohepatic cycle and chemical constitution of bile in such patients.", "contents": "[A clinical survey on 17 cases of cholelithiasis in childhood (author's transl)]. A series of 17 cases of gallstones in children observed over a period of 10 years in the area of Marseilles is described and the literature reviewed. The majority of children were girls over 10 years old. Symptoms were constantly present and the disease revealed nine times by acute \"mechanical\" cholecystitis, compared to 16 infectious cholecystitis followed during the same period, three times by an accident of migration (cholangitis in a 14 years old girl, bile ascitis in two infants). A cholecystography should be performed in acute recurrent abdominal pain of unknown origin in children, gallstones appearing to be radiotransparent in six patients. Among causes of gallstone formation, the authors dig out only 6 hemolytic anemias, related to hemoglobinopathies in three patients, and they emphasize the frequency of idiopathic cholelithiasis which should lead to a more complete investigation of the enterohepatic cycle and chemical constitution of bile in such patients."}
{"id": "PMID:220728", "title": "[Long-term therapy of osteoarthritis of the hip and the knee by sulindac (a cooperative trial in general practice) (author's transl)].", "content": "Long-term trial of sulindac (in general practice): 2,040 patients with osteoarthritis of the hip or of the knee been treated, 86,5% of them have been following the treatment for one year. This trial let us pointing out the non-improverishment of effectiveness of sulindac and the keepint of its good tolerance for long term. Some epidemiological data have been collected, among which: the importance of ponderal overload in patients studied and the prevalence of the right joints diseases on the left one's.", "contents": "[Long-term therapy of osteoarthritis of the hip and the knee by sulindac (a cooperative trial in general practice) (author's transl)]. Long-term trial of sulindac (in general practice): 2,040 patients with osteoarthritis of the hip or of the knee been treated, 86,5% of them have been following the treatment for one year. This trial let us pointing out the non-improverishment of effectiveness of sulindac and the keepint of its good tolerance for long term. Some epidemiological data have been collected, among which: the importance of ponderal overload in patients studied and the prevalence of the right joints diseases on the left one's."}
{"id": "PMID:220729", "title": "[Oral oestro-progestative contraception and cervical and vaginal cytology (author's transl)].", "content": "The cytological study of 1,685 smears belonging to women taking an oral contraception treatment, compared to 1,000 normal smears, shows that oestroprogestative drugs may be responsible for a certain number of more or less serious morphological disturbances in cervical and vaginal epithelial cells. These cell abnormalities, which correspond to inflammary of to slight dysphasia changes, are mostly spontaneously reversible or regress after cessation of the treatment. There does not seem to be a greater number of cervical cancers.", "contents": "[Oral oestro-progestative contraception and cervical and vaginal cytology (author's transl)]. The cytological study of 1,685 smears belonging to women taking an oral contraception treatment, compared to 1,000 normal smears, shows that oestroprogestative drugs may be responsible for a certain number of more or less serious morphological disturbances in cervical and vaginal epithelial cells. These cell abnormalities, which correspond to inflammary of to slight dysphasia changes, are mostly spontaneously reversible or regress after cessation of the treatment. There does not seem to be a greater number of cervical cancers."}
{"id": "PMID:220730", "title": "[Cytological diagnosis by punction of thyroid lesions. Histopathological correlations. Benign lesions (600 cases) (author's transl)].", "content": "Because of its important and its soft consistency, the thyroid is not always convenient for punction. Many smears cannot be classified, others are disappointing. The analysis of 2,300 punctions of thyroid lesions, allowed the authors to realise 900 comparisons between histopathological and cytological results. Among 300 histological malignant lesions, 89 unknown cancers were found, 40 of which gave haemorragic smears. The real false diagnosis were especially linked to vesicular and papillary carcinomas. On the other hand, undifferentiated carcinomas and lymphomas usually led to a correct interpretation. A correct diagnosis was made in 70% of all smears and in 81% of interpretable smears. The best results are found in benign lesions. The interpretation is correct in 94% of 600 punctions. A false diagnosis of malignancy is made in 6.1% of cases. So, this method fails to recognize an important number of cancers. It is not sufficient to assert the diagnosis and must be followed by an histopathological per-operatoire study. On the other hand a cytological diagnosis of cancer is reliable as long as the cytologist is not impressed by some cellular changes which are not so significant, as far as thyroid lesions are concerned, as in other fields of cytology.", "contents": "[Cytological diagnosis by punction of thyroid lesions. Histopathological correlations. Benign lesions (600 cases) (author's transl)]. Because of its important and its soft consistency, the thyroid is not always convenient for punction. Many smears cannot be classified, others are disappointing. The analysis of 2,300 punctions of thyroid lesions, allowed the authors to realise 900 comparisons between histopathological and cytological results. Among 300 histological malignant lesions, 89 unknown cancers were found, 40 of which gave haemorragic smears. The real false diagnosis were especially linked to vesicular and papillary carcinomas. On the other hand, undifferentiated carcinomas and lymphomas usually led to a correct interpretation. A correct diagnosis was made in 70% of all smears and in 81% of interpretable smears. The best results are found in benign lesions. The interpretation is correct in 94% of 600 punctions. A false diagnosis of malignancy is made in 6.1% of cases. So, this method fails to recognize an important number of cancers. It is not sufficient to assert the diagnosis and must be followed by an histopathological per-operatoire study. On the other hand a cytological diagnosis of cancer is reliable as long as the cytologist is not impressed by some cellular changes which are not so significant, as far as thyroid lesions are concerned, as in other fields of cytology."}
{"id": "PMID:220735", "title": "Endometrial hyperplasia: a five-year study.", "content": "Because of the recent controversy concerning estrogen and endometrial cancer, we studied the possible potential precursor lesions of the endometrium, reviewing 263 patients hospitalized in a community teaching hospital. The estrogen hormonal status, either exogenously or endogenously produced, plays a large role in the histologic structure of the uterine endometrium and may lead to difficulty in determining the exact histologic diagnosis or its potential to progress to endometrial adenocarcinoma.", "contents": "Endometrial hyperplasia: a five-year study. Because of the recent controversy concerning estrogen and endometrial cancer, we studied the possible potential precursor lesions of the endometrium, reviewing 263 patients hospitalized in a community teaching hospital. The estrogen hormonal status, either exogenously or endogenously produced, plays a large role in the histologic structure of the uterine endometrium and may lead to difficulty in determining the exact histologic diagnosis or its potential to progress to endometrial adenocarcinoma."}
{"id": "PMID:220731", "title": "[Statistical studies on hand accidents (author's transl)].", "content": "Statistics furnished by the French Social Security System covering 18 years (1957-1975) show not only the  marked frequency of injuries of the hand their financial, economic and social importance, but also an astonishing consistency of numbers over the years. This lack of improvement shows that (except in certain rare specialized centers) in general the treatment of hand injuries has minimally improved over the course of the last few decades while the rest of traumatology has made spectacular progress. This disastrous state of affairs should be addressed by medical and administrative authorities by improving the education and organizing the treatment of hand injuries.", "contents": "[Statistical studies on hand accidents (author's transl)]. Statistics furnished by the French Social Security System covering 18 years (1957-1975) show not only the  marked frequency of injuries of the hand their financial, economic and social importance, but also an astonishing consistency of numbers over the years. This lack of improvement shows that (except in certain rare specialized centers) in general the treatment of hand injuries has minimally improved over the course of the last few decades while the rest of traumatology has made spectacular progress. This disastrous state of affairs should be addressed by medical and administrative authorities by improving the education and organizing the treatment of hand injuries."}
{"id": "PMID:220736", "title": "Metastatic carcinoma with carcinocythemia mimicking leukemia.", "content": "Carcinoma metastatic to the bone marrow may present with peripheral blood and bone marrow changes and a clinical picture difficult to distinguish from leukemia. It is important to make an accurate diagnosis since the management is different. We have described a patient with circulating primitive cells and diffuse marrow involvement by similar cells. The pathologic process may be identified without cell markers by careful attention to the pattern of distribution, as well as the cytologic features of the neoplastic cells in the bone marrow biopsy.", "contents": "Metastatic carcinoma with carcinocythemia mimicking leukemia. Carcinoma metastatic to the bone marrow may present with peripheral blood and bone marrow changes and a clinical picture difficult to distinguish from leukemia. It is important to make an accurate diagnosis since the management is different. We have described a patient with circulating primitive cells and diffuse marrow involvement by similar cells. The pathologic process may be identified without cell markers by careful attention to the pattern of distribution, as well as the cytologic features of the neoplastic cells in the bone marrow biopsy."}
{"id": "PMID:220732", "title": "[Parathyroid adenoma induced by cervical radiotherapy].", "content": "The authors report one case of parathyroid adenoma in a 59 years old woman having received a cervical radiation therapy 38 years previously for suspected Basedow's disease. The cause and effect relationship between the cervical radiation and the appearance of the parathyroid adenoma seems to be established in the light of animal experimentation on one hand, and identical results found in the medical litterature on the other hand.", "contents": "[Parathyroid adenoma induced by cervical radiotherapy]. The authors report one case of parathyroid adenoma in a 59 years old woman having received a cervical radiation therapy 38 years previously for suspected Basedow's disease. The cause and effect relationship between the cervical radiation and the appearance of the parathyroid adenoma seems to be established in the light of animal experimentation on one hand, and identical results found in the medical litterature on the other hand."}
{"id": "PMID:220737", "title": "Ultrastructure of cholangiocarcinoma associated with opisthorchiasis.", "content": "An electron microscopic study was carried out on eleven surgical liver biopsy specimens obtained from patients with cholangiocarcinoma associated with opisthorchiasis. The tumor cells of histologically well differentiated cholangiocarcinoma had few cytoplasmic organelles. They contained relatively large nuclei, abundant free ribosomes and numerous groups of fine fibrils. Each cell was surrounded by a basement membrane. Numerous long microvilli were seen projecting into the glandular lumen. The moderately differentiated cholangiocarcinomatous cells exhibited increased organelle content, marked variation in the shape of the nuclei with deep cytoplasmic invagination into the nuclear membrane; there were small intranuclear pseudoinclusions, and shorter microvilli. The tumor cells showed intracellular microvillus-lined spaces, abundant free ribosomes, many fine fibrils and their surrounding basement membranes were incomplete. The ultrastructure of the poorly differentiated cholangiocarcinoma was similar to that of the moderately differentiated tumor, except for fewer microvilli, abundant cytoplasmic organelles, and ill-defined or absent basement membrane.", "contents": "Ultrastructure of cholangiocarcinoma associated with opisthorchiasis. An electron microscopic study was carried out on eleven surgical liver biopsy specimens obtained from patients with cholangiocarcinoma associated with opisthorchiasis. The tumor cells of histologically well differentiated cholangiocarcinoma had few cytoplasmic organelles. They contained relatively large nuclei, abundant free ribosomes and numerous groups of fine fibrils. Each cell was surrounded by a basement membrane. Numerous long microvilli were seen projecting into the glandular lumen. The moderately differentiated cholangiocarcinomatous cells exhibited increased organelle content, marked variation in the shape of the nuclei with deep cytoplasmic invagination into the nuclear membrane; there were small intranuclear pseudoinclusions, and shorter microvilli. The tumor cells showed intracellular microvillus-lined spaces, abundant free ribosomes, many fine fibrils and their surrounding basement membranes were incomplete. The ultrastructure of the poorly differentiated cholangiocarcinoma was similar to that of the moderately differentiated tumor, except for fewer microvilli, abundant cytoplasmic organelles, and ill-defined or absent basement membrane."}
{"id": "PMID:220741", "title": "Colloid adenocarcinoma of the caecum in a 13-year-old. A case report.", "content": "A 13-year-old Coloured girl presented with an abdominal mass and a small-bowel obstruction. At operation a constricting carcinoma of the caecum which had spread to the regional lymph nodes was found. Histological examination revealed that it was a mucinous adenocarcinoma.", "contents": "Colloid adenocarcinoma of the caecum in a 13-year-old. A case report. A 13-year-old Coloured girl presented with an abdominal mass and a small-bowel obstruction. At operation a constricting carcinoma of the caecum which had spread to the regional lymph nodes was found. Histological examination revealed that it was a mucinous adenocarcinoma."}
{"id": "PMID:220745", "title": "Surgical treatment of ulnar neuropathy.", "content": "Ulnar neuropathy is a well recognized clinical entity caused by a variety of pathological lesions around the elbow. The characteristic features include paresthesia and numbness in the little finger and medial half of the fourth digit, weakness of the small muscles of the hand innervated by the ulnar nerve, and a positive Tinel's sign. The diagnosis is confirmed by electrophysiological studies. Current methods of treatment are anterior transposition, neurolysis and medial epicondylectomy of the humerus. Forty-four patients with ulnar neuropathy are described in the present report. Most were males with a median age of 45. The left side was involved more frequently. Results of subcutaneous anterior transposition and medial epicondylectomy are presented along with a review of the literature.", "contents": "Surgical treatment of ulnar neuropathy. Ulnar neuropathy is a well recognized clinical entity caused by a variety of pathological lesions around the elbow. The characteristic features include paresthesia and numbness in the little finger and medial half of the fourth digit, weakness of the small muscles of the hand innervated by the ulnar nerve, and a positive Tinel's sign. The diagnosis is confirmed by electrophysiological studies. Current methods of treatment are anterior transposition, neurolysis and medial epicondylectomy of the humerus. Forty-four patients with ulnar neuropathy are described in the present report. Most were males with a median age of 45. The left side was involved more frequently. Results of subcutaneous anterior transposition and medial epicondylectomy are presented along with a review of the literature."}
{"id": "PMID:220747", "title": "Respiratory viral infection and wheezy bronchitis in childhood.", "content": "The role of respiratory viral infection in wheezy bronchitis was studied in 163 children, aged 0-12 years, in a London general practice. Virological investigations were also performed when these same children had acute upper respiratory illness without wheeze. A virus was isolated in 146 (26.4%) of 554 episodes of wheezy bronchitis, rhinoviruses accounting for almost half of the isolations. The relative frequency with which individual viruses were isolated in wheezy bronchitis was similar to that in acute upper respiratory illness in 180 other children who had never had wheezy bronchitis. The large number of isolations of rhinoviruses in wheezy bronchitis is probably due to their numerous serotypes and the absence of cross-immunity between them. Our findings have confirmed that infection by respiratory viruses can provoke wheezy bronchitis in certain children, in whom host factors are an important predeterminant. In children with a previous history of wheezy bronchitis infection by rhinoviruses was associated significantly more often with such an episode than with upper respiratory illness. The maturation of protective mechanisms, including the acquisition of specific immunity to a progressively larger number of viruses, could explain the fall in the age-incidence of wheezy bronchitis.", "contents": "Respiratory viral infection and wheezy bronchitis in childhood. The role of respiratory viral infection in wheezy bronchitis was studied in 163 children, aged 0-12 years, in a London general practice. Virological investigations were also performed when these same children had acute upper respiratory illness without wheeze. A virus was isolated in 146 (26.4%) of 554 episodes of wheezy bronchitis, rhinoviruses accounting for almost half of the isolations. The relative frequency with which individual viruses were isolated in wheezy bronchitis was similar to that in acute upper respiratory illness in 180 other children who had never had wheezy bronchitis. The large number of isolations of rhinoviruses in wheezy bronchitis is probably due to their numerous serotypes and the absence of cross-immunity between them. Our findings have confirmed that infection by respiratory viruses can provoke wheezy bronchitis in certain children, in whom host factors are an important predeterminant. In children with a previous history of wheezy bronchitis infection by rhinoviruses was associated significantly more often with such an episode than with upper respiratory illness. The maturation of protective mechanisms, including the acquisition of specific immunity to a progressively larger number of viruses, could explain the fall in the age-incidence of wheezy bronchitis."}
{"id": "PMID:220748", "title": "Value of measuring serum angiotensin I converting enzyme and serum lysozyme in the management of sarcoidosis.", "content": "Serum angiotensin I converting enzyme (ACE) and lysozyme have been measured in 23 controls, 115 patients with sarcoidosis, and 64 with other chest diseases. Both enzymes were significantly raised in sarcoidosis. ACE was raised above the normal range in 21 of 72 (29%) patients with definite sarcoidosis and in 17 of 38 (45%) of those who were untreated and seen within one year of presentation. The rise discriminated usefully between those with stable and progressive disease (5% and 62% respectively). Lysozyme was raised in 50 of 72 (69%) patients with sarcoidosis but also in 11 of 54 (20%) patients with other chest diseases. Discrimination between stable and progressive disease was useful only if very high levels were considered. Five patients had serial measurements after treatment with oral steroids and showed a progressive fall in levals of both enzymes, but patients with other diseases also showed a significant fall within the normal range when so treated. Measurement of these enzymes may help in the management of some cases of sarcoidosis, but results require critical interpretation.", "contents": "Value of measuring serum angiotensin I converting enzyme and serum lysozyme in the management of sarcoidosis. Serum angiotensin I converting enzyme (ACE) and lysozyme have been measured in 23 controls, 115 patients with sarcoidosis, and 64 with other chest diseases. Both enzymes were significantly raised in sarcoidosis. ACE was raised above the normal range in 21 of 72 (29%) patients with definite sarcoidosis and in 17 of 38 (45%) of those who were untreated and seen within one year of presentation. The rise discriminated usefully between those with stable and progressive disease (5% and 62% respectively). Lysozyme was raised in 50 of 72 (69%) patients with sarcoidosis but also in 11 of 54 (20%) patients with other chest diseases. Discrimination between stable and progressive disease was useful only if very high levels were considered. Five patients had serial measurements after treatment with oral steroids and showed a progressive fall in levals of both enzymes, but patients with other diseases also showed a significant fall within the normal range when so treated. Measurement of these enzymes may help in the management of some cases of sarcoidosis, but results require critical interpretation."}
{"id": "PMID:220751", "title": "An out-break of acute gastroenteritis due to rotavirus in an infant home.", "content": "In December 1976, an outbreak of acute infectious diarrhea occurred among infants who resided in an infant home in the city of Sapporo. Rotavirus infection was proved in 42 (90%) of 47 infants by serologic and/or electron microscopic examinations. Out of 42 infected infants 38(90%) were clinically affected; diarrhea with or without vomiting in 27 (64%), vomiting without diarrhea in 6 (14%) and only febrile episode in 5 (12%). The remaining 4(10%) infants showed no symptoms. Clinical manifestations seemed to differ depending on age. Diarrhea without vomiting was more common in the patients younger than 6 months of age, and vomiting or fever was more common in the groups of older age. Possible reasons for such an age dependency were discussed on the basis of complement-fixation tests using human and calf strains of rotavirus.", "contents": "An out-break of acute gastroenteritis due to rotavirus in an infant home. In December 1976, an outbreak of acute infectious diarrhea occurred among infants who resided in an infant home in the city of Sapporo. Rotavirus infection was proved in 42 (90%) of 47 infants by serologic and/or electron microscopic examinations. Out of 42 infected infants 38(90%) were clinically affected; diarrhea with or without vomiting in 27 (64%), vomiting without diarrhea in 6 (14%) and only febrile episode in 5 (12%). The remaining 4(10%) infants showed no symptoms. Clinical manifestations seemed to differ depending on age. Diarrhea without vomiting was more common in the patients younger than 6 months of age, and vomiting or fever was more common in the groups of older age. Possible reasons for such an age dependency were discussed on the basis of complement-fixation tests using human and calf strains of rotavirus."}
{"id": "PMID:220752", "title": "Electron microscopic studies on transplantable mucus-secreting and tubular adenocarcinomas of colo-rectal origin in ACI/N rats.", "content": "Two transplantable, one mucus-producing (R-1) and the other tubular but less mucinous (R-2), adenocarcinomas were investigated electron microscopically. The R-1 tumor was composed of a large number of intermediate cells and mucus-producing cells, incompletely differentiated goblet-like cells and absorptive-like cells, and a small number of undifferentiated cells. The electron microscopic features of the mucus-producing cells exhibited distinctive features different from those of the epithelium of normal colon. They had highly electron-dense granules, expanded rER, well-developed mitochondria and Golgi apparatus. The R-1 tumor was found to be a well-differentiated adenocarcinoma in agreement with observations by light microscopy, while the R-2 tumor exhibited more malignant features than R-1.", "contents": "Electron microscopic studies on transplantable mucus-secreting and tubular adenocarcinomas of colo-rectal origin in ACI/N rats. Two transplantable, one mucus-producing (R-1) and the other tubular but less mucinous (R-2), adenocarcinomas were investigated electron microscopically. The R-1 tumor was composed of a large number of intermediate cells and mucus-producing cells, incompletely differentiated goblet-like cells and absorptive-like cells, and a small number of undifferentiated cells. The electron microscopic features of the mucus-producing cells exhibited distinctive features different from those of the epithelium of normal colon. They had highly electron-dense granules, expanded rER, well-developed mitochondria and Golgi apparatus. The R-1 tumor was found to be a well-differentiated adenocarcinoma in agreement with observations by light microscopy, while the R-2 tumor exhibited more malignant features than R-1."}
{"id": "PMID:220754", "title": "An improved procedure for the preparation of rat uterine cell suspensions.", "content": "In the present paper we report on an improved procedure for the preparation of free uterine cells which avoids the use of trypsin and employs very low concentration of collagenase. The cells released mechanically from the digested tissue are constantly removed from the enzyme containing medium, thus minimizing exposure to collagenase. 60%-70% of the cells which make up the intact uterus are obtained as free cells and 95% of these cells are viable for at least 15 hours at 37 degrees. Metabolic integrity was assessed by measuring the cell's ability to oxidize glucose and synthesize proteins over extended periods of time. The membrane leucine carrier protein and the membrane Na+/K+ ATPase were found to be fully functional. Electron microscopic analysis of the cells confirmed their structural integrity. Data are presented illustrating that with this system the estrogen binding protein is stable at physiological temperatures. The cells contain approximately 30,000 specific estrogen binding sites, with an apparent KA of 5--6 x 10(9) M-1. At 37 degrees 80% of the hormone receptor complexes were in the nuclear fraction, 20% in the cytoplasm. The similarity of the estrogen receptor binding parameters with those measured in the intact tissue after in vivo hormone adminsistration, together with the cells' structural and metabolic integrity make this procedure for the preparation of uterine cell suspensions in high yields particularly suitable for studies in which minimal cell injury is an essential prerequisite.", "contents": "An improved procedure for the preparation of rat uterine cell suspensions. In the present paper we report on an improved procedure for the preparation of free uterine cells which avoids the use of trypsin and employs very low concentration of collagenase. The cells released mechanically from the digested tissue are constantly removed from the enzyme containing medium, thus minimizing exposure to collagenase. 60%-70% of the cells which make up the intact uterus are obtained as free cells and 95% of these cells are viable for at least 15 hours at 37 degrees. Metabolic integrity was assessed by measuring the cell's ability to oxidize glucose and synthesize proteins over extended periods of time. The membrane leucine carrier protein and the membrane Na+/K+ ATPase were found to be fully functional. Electron microscopic analysis of the cells confirmed their structural integrity. Data are presented illustrating that with this system the estrogen binding protein is stable at physiological temperatures. The cells contain approximately 30,000 specific estrogen binding sites, with an apparent KA of 5--6 x 10(9) M-1. At 37 degrees 80% of the hormone receptor complexes were in the nuclear fraction, 20% in the cytoplasm. The similarity of the estrogen receptor binding parameters with those measured in the intact tissue after in vivo hormone adminsistration, together with the cells' structural and metabolic integrity make this procedure for the preparation of uterine cell suspensions in high yields particularly suitable for studies in which minimal cell injury is an essential prerequisite."}
{"id": "PMID:220755", "title": "Adrenergic control of cerebral blood flow and energy metabolism in the rat.", "content": "Studies in rats were designed to separate and define the roles of the intrinsic and extrinsic adrenergic neurons in the control of cerebral blood flow (CBF) and cerebral energy metabolism. The data suggest several conclusions: 1. Arterial sympathetic innervation plays a role in the autoregulation of cerebral circulation. 2. The central adrenergic neurons have several functions: a) they enhance cerebral vascular tone by action on alpha receptor sites. b) They play an important role in the metabolic control of CBF. The proton-sensitive receptor sites on blood vessel walls require beta-adrenergic input in order to function. c) They influence metabolic rate of brain tissue by acting on beta-receptor sites on the cell membrane.", "contents": "Adrenergic control of cerebral blood flow and energy metabolism in the rat. Studies in rats were designed to separate and define the roles of the intrinsic and extrinsic adrenergic neurons in the control of cerebral blood flow (CBF) and cerebral energy metabolism. The data suggest several conclusions: 1. Arterial sympathetic innervation plays a role in the autoregulation of cerebral circulation. 2. The central adrenergic neurons have several functions: a) they enhance cerebral vascular tone by action on alpha receptor sites. b) They play an important role in the metabolic control of CBF. The proton-sensitive receptor sites on blood vessel walls require beta-adrenergic input in order to function. c) They influence metabolic rate of brain tissue by acting on beta-receptor sites on the cell membrane."}
{"id": "PMID:220760", "title": "Evaluation of parasitological and serological techniques in diagnosis of amoebiasis.", "content": "Parasitological investigations carried out on 324 subjects of symptomatic and asymptomatic amoebiasis showed that formol-ether concentration was a superior technique than examination of 3 consecutive stool specimens by direct microscopy in cases of colitis, hepatitis and cyst passers. Culture of pus yielded better results than the other techniques for examination of stool in cases of liver abscess. Indirect haemagglutination test carried out with 238 sera from cases confirmed to be either positive or negative for Entamoeba histolytica revealed good correlation of its results with parasitological investigations in cases of dysentery and hepatitis. This test proved to be much superior to parasitological investigations in diagnosis of liver abscess. A close correlation between the results of gel-diffusion and I.H.A. was observed in dysentery and liver abscess groups, although I.H.A. was more sensitive. Precipitin band appeared in gel-diffusion test only when the I.H.A. titre was 1: 486 and the number of bands increased with rise in the titre.", "contents": "Evaluation of parasitological and serological techniques in diagnosis of amoebiasis. Parasitological investigations carried out on 324 subjects of symptomatic and asymptomatic amoebiasis showed that formol-ether concentration was a superior technique than examination of 3 consecutive stool specimens by direct microscopy in cases of colitis, hepatitis and cyst passers. Culture of pus yielded better results than the other techniques for examination of stool in cases of liver abscess. Indirect haemagglutination test carried out with 238 sera from cases confirmed to be either positive or negative for Entamoeba histolytica revealed good correlation of its results with parasitological investigations in cases of dysentery and hepatitis. This test proved to be much superior to parasitological investigations in diagnosis of liver abscess. A close correlation between the results of gel-diffusion and I.H.A. was observed in dysentery and liver abscess groups, although I.H.A. was more sensitive. Precipitin band appeared in gel-diffusion test only when the I.H.A. titre was 1: 486 and the number of bands increased with rise in the titre."}
{"id": "PMID:220761", "title": "Bluetongue antibody in Botswana's domestic and game animals.", "content": "Bluetongue precipitating antibody was demonstrated in sera of cattle, camels, sheep, goats and seven game species. Of the domestic species the percentage of sera positive were; cattle 92%, camels 81%, goats 83% and sheep 36%. Sheep sera, unlike those of other domestic species, varied greatly from area to area in the percentage positive. Seroconversions were recorded in adult sheep between September and April. In adult cattle there was a gradual decline in the percentage positive with increasing age. Positive reactions were recorded in the following game species: impala (Aepyceros melampus), lechwe (Kobus leche), kudu (Tragelaphus strepsiceros), blue wildebeest (Connochaetes taurinus), gemsbok (Oryx gazella), springbok (Antidorcas marsupialis) and tsessebe (Damaliscus lunatus).", "contents": "Bluetongue antibody in Botswana's domestic and game animals. Bluetongue precipitating antibody was demonstrated in sera of cattle, camels, sheep, goats and seven game species. Of the domestic species the percentage of sera positive were; cattle 92%, camels 81%, goats 83% and sheep 36%. Sheep sera, unlike those of other domestic species, varied greatly from area to area in the percentage positive. Seroconversions were recorded in adult sheep between September and April. In adult cattle there was a gradual decline in the percentage positive with increasing age. Positive reactions were recorded in the following game species: impala (Aepyceros melampus), lechwe (Kobus leche), kudu (Tragelaphus strepsiceros), blue wildebeest (Connochaetes taurinus), gemsbok (Oryx gazella), springbok (Antidorcas marsupialis) and tsessebe (Damaliscus lunatus)."}
{"id": "PMID:220762", "title": "Evolution of primary tumors induced in adult mice by MSV-H and MSV-H producer tumor cells.", "content": "The oncogenic activity of both MSV-H and MSV-H-producer tumor cells (3T3 + MSV-H) in adult mice was investigated and compared. A higher incidence of tumors was observed with MSV-H tumor cells, especially with very small tumor cell doses. No regression was observed in any of the induced tumors.", "contents": "Evolution of primary tumors induced in adult mice by MSV-H and MSV-H producer tumor cells. The oncogenic activity of both MSV-H and MSV-H-producer tumor cells (3T3 + MSV-H) in adult mice was investigated and compared. A higher incidence of tumors was observed with MSV-H tumor cells, especially with very small tumor cell doses. No regression was observed in any of the induced tumors."}
{"id": "PMID:220763", "title": "Analysis of some factors effecting survival in malignant gliomas.", "content": "Many factors, including the histological aspect, are known to effect the survival of patients with malignant gliomas. The relation between survival and diagnoses such as primary and secondary glioblastoma, anaplastic astrocytoma, etc., is not definitely clear. In 324 malignant gliomas the relationship between survival and age, sex, tumor pathology, occurrence of lymphoplasmacytic infiltrations, and size of the examined specimen was studied. Preoperative intervals of primary and secondary glioblastomas do not differ; anaplastic astrocytomas show definitely longer preoperative intervals and slightly but not significantly longer postoperative patient survival. The correlations are discussed, focusing on importance of knowing the survival times of untreated cases in order to evaluate the efficacy of chemotherapeutic drugs in malignant gliomas.", "contents": "Analysis of some factors effecting survival in malignant gliomas. Many factors, including the histological aspect, are known to effect the survival of patients with malignant gliomas. The relation between survival and diagnoses such as primary and secondary glioblastoma, anaplastic astrocytoma, etc., is not definitely clear. In 324 malignant gliomas the relationship between survival and age, sex, tumor pathology, occurrence of lymphoplasmacytic infiltrations, and size of the examined specimen was studied. Preoperative intervals of primary and secondary glioblastomas do not differ; anaplastic astrocytomas show definitely longer preoperative intervals and slightly but not significantly longer postoperative patient survival. The correlations are discussed, focusing on importance of knowing the survival times of untreated cases in order to evaluate the efficacy of chemotherapeutic drugs in malignant gliomas."}
{"id": "PMID:220766", "title": "On the relation between peripheral atherosclerosis and serum lipoproteins.", "content": "The occurrence and degree of peripheral atherosclerosis in 30 male patients with symptoms of intermittent claudication were studied by arteriography. The changes observed in the angiograms were codified. In all patients the concentrations of triglycerides and cholesterol were determined in whole serum and in the three major lipoprotein classes--very low density, low density and high density lipoproteins. These data were compared with those of a control material and were also correlated to the codified angiographic findings in each individual patient. Positive significant correlation was not found between the arteriographic changes and the serum concentrations of lipids and lipoproteins, which might be explained by an advanced stage of the disease where such relationships might not appear.", "contents": "On the relation between peripheral atherosclerosis and serum lipoproteins. The occurrence and degree of peripheral atherosclerosis in 30 male patients with symptoms of intermittent claudication were studied by arteriography. The changes observed in the angiograms were codified. In all patients the concentrations of triglycerides and cholesterol were determined in whole serum and in the three major lipoprotein classes--very low density, low density and high density lipoproteins. These data were compared with those of a control material and were also correlated to the codified angiographic findings in each individual patient. Positive significant correlation was not found between the arteriographic changes and the serum concentrations of lipids and lipoproteins, which might be explained by an advanced stage of the disease where such relationships might not appear."}
{"id": "PMID:220767", "title": "Management of neurogenic bladder in infancy and childhood.", "content": "Sixty-two patients, age twelve years and under, were treated for incontinence due to neurogenic bladder secondary to spina bifida (58) or trauma (4) with a follow-up period of three to thirty-two months (mean, ten months). In early life, patients were managed with the Cred\u00e9 maneuver (18 patients). Older children were managed with intermittent clean catheterization (44 patients) with or without pharmacologic agents. Continence was achieved with intermittent clean catheterization in 77 per cent, thus enabling these children to be more acceptable to their peers and in many cases attend schools from which they had previously been excluded because of urinary incontinence. With the Cred\u00e9 maneuver, renal deterioration was noted in 11 per cent on follow-up IVP, and in 2 per cent of the patients on intermittent clean catheterization. Recurrent asymptomatic bacteriuria occurred in 33 per cent of those with the Cred\u00e9 maneuver and in 55 per cent of the patients using intermittent clean catheterization. The use of antibiotic bladder irrigations reduced this incidence to 5 per cent. All patients with renal deterioration except one responded to intermittent clean catheterization; this patient was treated with cutaneous vesicostomy. Urodynamic assessment was performed in 15 patients, and this diagnostic tool assisted in the therapeutic management of these children.", "contents": "Management of neurogenic bladder in infancy and childhood. Sixty-two patients, age twelve years and under, were treated for incontinence due to neurogenic bladder secondary to spina bifida (58) or trauma (4) with a follow-up period of three to thirty-two months (mean, ten months). In early life, patients were managed with the Cred\u00e9 maneuver (18 patients). Older children were managed with intermittent clean catheterization (44 patients) with or without pharmacologic agents. Continence was achieved with intermittent clean catheterization in 77 per cent, thus enabling these children to be more acceptable to their peers and in many cases attend schools from which they had previously been excluded because of urinary incontinence. With the Cred\u00e9 maneuver, renal deterioration was noted in 11 per cent on follow-up IVP, and in 2 per cent of the patients on intermittent clean catheterization. Recurrent asymptomatic bacteriuria occurred in 33 per cent of those with the Cred\u00e9 maneuver and in 55 per cent of the patients using intermittent clean catheterization. The use of antibiotic bladder irrigations reduced this incidence to 5 per cent. All patients with renal deterioration except one responded to intermittent clean catheterization; this patient was treated with cutaneous vesicostomy. Urodynamic assessment was performed in 15 patients, and this diagnostic tool assisted in the therapeutic management of these children."}
{"id": "PMID:220769", "title": "[Effect of dibazol on the state of the hypophyseal-adrenal system in patients operated on under thiopental anesthesia].", "content": "In the observations over the patients subjected to operations on the limbs under thiopental narcosis and in the experiments on white rats exposed to a shockogenic trauma (by Kennon's method) it has been found that the prophylactic injection of 1--2 mg/kg dose of dibazol rises the non-specific resistance of the body. The hormones of the pituitary-adrenal system have been found to hold an important place in the mechanism of the effect of dibazol.", "contents": "[Effect of dibazol on the state of the hypophyseal-adrenal system in patients operated on under thiopental anesthesia]. In the observations over the patients subjected to operations on the limbs under thiopental narcosis and in the experiments on white rats exposed to a shockogenic trauma (by Kennon's method) it has been found that the prophylactic injection of 1--2 mg/kg dose of dibazol rises the non-specific resistance of the body. The hormones of the pituitary-adrenal system have been found to hold an important place in the mechanism of the effect of dibazol."}
{"id": "PMID:220772", "title": "Immunologic methods for the detection of humoral and cellular immunity.", "content": "A variety of immunologic techniques have been introduced during the past few years. Many of these techniques are being applied to clinical specimens in an attempt to help the practicing veterinarian make a diagnosis. The introduction of new techniques requires extensive testing with clinically normal and diseased patients. It is essential for the practicing veterinarian to understand that the techniques available for the detection of immunologic disorders in the dog and cat are not routine diagnostic procedures and that adequate information has not been developed for any of the techniques described to assure the clinical significance of either positive or negative results (Table 3). This should not discourage the practitioner from submitting samples, but should encourage him or her to question the significance of those results and to attempt to correlate them with history and clinical signs before arriving at a final diagnosis.", "contents": "Immunologic methods for the detection of humoral and cellular immunity. A variety of immunologic techniques have been introduced during the past few years. Many of these techniques are being applied to clinical specimens in an attempt to help the practicing veterinarian make a diagnosis. The introduction of new techniques requires extensive testing with clinically normal and diseased patients. It is essential for the practicing veterinarian to understand that the techniques available for the detection of immunologic disorders in the dog and cat are not routine diagnostic procedures and that adequate information has not been developed for any of the techniques described to assure the clinical significance of either positive or negative results (Table 3). This should not discourage the practitioner from submitting samples, but should encourage him or her to question the significance of those results and to attempt to correlate them with history and clinical signs before arriving at a final diagnosis."}
{"id": "PMID:220774", "title": "Frequency of canine and feline tumors in a defined population.", "content": "The Tulsa Registry of Canine and Feline Neoplasms was the second animal tumor registry in the United States concerned with a defined population in a delimited geographic area. Only tumors histologically confirmed by registry pathologists were included in frequency statistics based on the annual dog and cat population presented to veterinarians. During the first registry year, about 1% of the 63,504 dogs and 0.5% of the 11,909 cats had one or more primary tumors. While the incidence rate for malignant tumors in dogs was similar to that in cats, the incidence of benign tumors of dogs was over 10 times that of cats. The most common tumors were sebaceous adenoma in dogs and lymphosarcoma in cats. Mammary cancer was the most common malignant tumor in dogs. Mammary tumors of female dogs were significantly more frequent in Pointers, Poodles and Boston Terriers, in that order, than in other breeds. A greater incidence of mammary tumors among intact compared to spayed female dogs was seen for virtually every age group except in the Pointer breed.", "contents": "Frequency of canine and feline tumors in a defined population. The Tulsa Registry of Canine and Feline Neoplasms was the second animal tumor registry in the United States concerned with a defined population in a delimited geographic area. Only tumors histologically confirmed by registry pathologists were included in frequency statistics based on the annual dog and cat population presented to veterinarians. During the first registry year, about 1% of the 63,504 dogs and 0.5% of the 11,909 cats had one or more primary tumors. While the incidence rate for malignant tumors in dogs was similar to that in cats, the incidence of benign tumors of dogs was over 10 times that of cats. The most common tumors were sebaceous adenoma in dogs and lymphosarcoma in cats. Mammary cancer was the most common malignant tumor in dogs. Mammary tumors of female dogs were significantly more frequent in Pointers, Poodles and Boston Terriers, in that order, than in other breeds. A greater incidence of mammary tumors among intact compared to spayed female dogs was seen for virtually every age group except in the Pointer breed."}
{"id": "PMID:220775", "title": "Granular cell variants in a rat schwannoma. Evidence of neurogenic origin of granular cell tumor (myoblastoma).", "content": "A large, intraabdominal rat schwannoma had numerous granule-containing cells cytologically identical to cells of granular cell tumor (myoblastoma). The small eosinophilic granules stained positively by the periodic acid-Schiff (PAS) reaction, with intensity not reduced by diastase pretreatment. Granules stained positively with the Tibor Pap silver impregnation for reticulin and by electron microscopy were identical to myoblastoma cell granules. The nuclei of granular cells were morphologically identical to those of the neoplastic Schwann cells. The granular cells were in numerous foci within the tumor, frequently were seen in mitosis, and possessed an extremely variable volume of cytoplasm. They seemed to evolve from neoplastic Schwann cells. Cells with only a narrow perinuclear rim of granular cytoplasm were of the same size and general configuration as adjacent neoplastic Schwann cells, while cells with increasing volumes of granular cytoplasm were increasingly swollen and round. One area of the tumor was composed almost entirely of such large cells and was histologically identical to classic granular cell tumor.", "contents": "Granular cell variants in a rat schwannoma. Evidence of neurogenic origin of granular cell tumor (myoblastoma). A large, intraabdominal rat schwannoma had numerous granule-containing cells cytologically identical to cells of granular cell tumor (myoblastoma). The small eosinophilic granules stained positively by the periodic acid-Schiff (PAS) reaction, with intensity not reduced by diastase pretreatment. Granules stained positively with the Tibor Pap silver impregnation for reticulin and by electron microscopy were identical to myoblastoma cell granules. The nuclei of granular cells were morphologically identical to those of the neoplastic Schwann cells. The granular cells were in numerous foci within the tumor, frequently were seen in mitosis, and possessed an extremely variable volume of cytoplasm. They seemed to evolve from neoplastic Schwann cells. Cells with only a narrow perinuclear rim of granular cytoplasm were of the same size and general configuration as adjacent neoplastic Schwann cells, while cells with increasing volumes of granular cytoplasm were increasingly swollen and round. One area of the tumor was composed almost entirely of such large cells and was histologically identical to classic granular cell tumor."}
{"id": "PMID:220776", "title": "Effects of anabolic steroids on liver cell ultrastructure in sheep.", "content": "Castrated male sheep were sham inplanted or implanted with estradiol, trenbolone acetate or trenbolone acetate in combination with estradiol, and slaughtered after 56 days. Ultrastructural and morphometric examination of the livers of steroid-treated sheep showed an increase in the volume density of the cell occupied by rough endoplasmic reticulum and microbodies. In four of the eight sheep treated with trenbolone acetate, either alone or in combination with estradiol, enlarged mitochondria with crystalline inclusions were seen. The increase in hepatic rough endoplasmic reticulum may be of benefit to the sheep whereas the mitochondrial changes after anabolic steroid use indicate a cellular lesion of unknown significance for health.", "contents": "Effects of anabolic steroids on liver cell ultrastructure in sheep. Castrated male sheep were sham inplanted or implanted with estradiol, trenbolone acetate or trenbolone acetate in combination with estradiol, and slaughtered after 56 days. Ultrastructural and morphometric examination of the livers of steroid-treated sheep showed an increase in the volume density of the cell occupied by rough endoplasmic reticulum and microbodies. In four of the eight sheep treated with trenbolone acetate, either alone or in combination with estradiol, enlarged mitochondria with crystalline inclusions were seen. The increase in hepatic rough endoplasmic reticulum may be of benefit to the sheep whereas the mitochondrial changes after anabolic steroid use indicate a cellular lesion of unknown significance for health."}
{"id": "PMID:220777", "title": "Malignant fibrous histiocytoma in dogs and cats.", "content": "Five soft tissue tumors of varied morphology in dogs and cats were classified as malignant fibrous histiocytomas on the basis of their histologic composition. All were composed of varying mixtures of histiocytes and fibroblasts and three contained large multinucleated cells. This giant cell variant of malignant fibrous histiocytoma was seen only in cats. These tumors are comparable to those described in man as malignant fibrous histiocytoma on the basis of the malignant histiocyte and its varied morphology and function.", "contents": "Malignant fibrous histiocytoma in dogs and cats. Five soft tissue tumors of varied morphology in dogs and cats were classified as malignant fibrous histiocytomas on the basis of their histologic composition. All were composed of varying mixtures of histiocytes and fibroblasts and three contained large multinucleated cells. This giant cell variant of malignant fibrous histiocytoma was seen only in cats. These tumors are comparable to those described in man as malignant fibrous histiocytoma on the basis of the malignant histiocyte and its varied morphology and function."}
{"id": "PMID:220780", "title": "Ultrastructural and histological study of 11 bronchial carcinoids. Evidence for different types.", "content": "Seven of eleven bronchial carcinoids investigated showed cells with small granules resembling P cells which have already been described in human fetal and adult lung; two of these P cell tumours showed distinctive paraganglioid features. One tumour showed peculiar ultrastructural findings resembling closely those previously reported by Black (1969) in a so called \"pulmonary oncocytoma\". Three remaining cases showed large secretory granules resembling those of type 3 cells already described by Hage (1973b) in bronchial carcinoids; one of these tumours produced large amounts of 5-hydroxytryptamine (5HT). It is concluded that, on cytological grounds, at least two types of tumours can be distinguished among bronchial carcinoids, i.e. P cell and type 3 cell tumours. Moreover, two varieties of P cell carcinoids have been recognized, showing either the less frequent and more distinctive paraganglioid structure or the more common trabecular structure.", "contents": "Ultrastructural and histological study of 11 bronchial carcinoids. Evidence for different types. Seven of eleven bronchial carcinoids investigated showed cells with small granules resembling P cells which have already been described in human fetal and adult lung; two of these P cell tumours showed distinctive paraganglioid features. One tumour showed peculiar ultrastructural findings resembling closely those previously reported by Black (1969) in a so called \"pulmonary oncocytoma\". Three remaining cases showed large secretory granules resembling those of type 3 cells already described by Hage (1973b) in bronchial carcinoids; one of these tumours produced large amounts of 5-hydroxytryptamine (5HT). It is concluded that, on cytological grounds, at least two types of tumours can be distinguished among bronchial carcinoids, i.e. P cell and type 3 cell tumours. Moreover, two varieties of P cell carcinoids have been recognized, showing either the less frequent and more distinctive paraganglioid structure or the more common trabecular structure."}
{"id": "PMID:220800", "title": "[Isolation and properties of myeloperoxidase from human bone marrow].", "content": "A preparation of myeloperoxidase was isolated from human bone marrow by column chromatography on DEAE-Sephadex, CM cellulose and gel filtration on Sephadex G-100. The enzyme was purified to 0.76 purity with a 16% yield. The repeated gel filtration, E430/E280 ratio and immunochemical study confirm the high degree of purification. Molecular weight of the enzyme, determined by gel filtration on Sephadex G-100, was 150000.", "contents": "[Isolation and properties of myeloperoxidase from human bone marrow]. A preparation of myeloperoxidase was isolated from human bone marrow by column chromatography on DEAE-Sephadex, CM cellulose and gel filtration on Sephadex G-100. The enzyme was purified to 0.76 purity with a 16% yield. The repeated gel filtration, E430/E280 ratio and immunochemical study confirm the high degree of purification. Molecular weight of the enzyme, determined by gel filtration on Sephadex G-100, was 150000."}
{"id": "PMID:220801", "title": "[Effect of oxythiamine on pyruvate and lactate metabolism in rat tissues].", "content": "The ratio of two substrates (pyruvate and lactate), activity of enzymes, responsible for their turnover in liver tissue, sceletal muscles and blood, were studied simultaneously in experiments on the effect of hydroxythiamin, which was administered at doses, causing a state of hypovitaminosis B1. Hydroxythiamin was shown to inhibit specifically the activity of thiamin-dependent enzymes (transketolase and pyruvate dehydrogenase). It affected also the metabolism of triose phosphates, pyruvate and lactate. At the same time, hydroxythiamin was responsible for changes in activities of other enzymes, participating in turnover of the substrates studied.", "contents": "[Effect of oxythiamine on pyruvate and lactate metabolism in rat tissues]. The ratio of two substrates (pyruvate and lactate), activity of enzymes, responsible for their turnover in liver tissue, sceletal muscles and blood, were studied simultaneously in experiments on the effect of hydroxythiamin, which was administered at doses, causing a state of hypovitaminosis B1. Hydroxythiamin was shown to inhibit specifically the activity of thiamin-dependent enzymes (transketolase and pyruvate dehydrogenase). It affected also the metabolism of triose phosphates, pyruvate and lactate. At the same time, hydroxythiamin was responsible for changes in activities of other enzymes, participating in turnover of the substrates studied."}
{"id": "PMID:220799", "title": "[Relation of urinary excretion of cholesterol in cancer patients to certain hormonal-metabolic parameters and the effect of drugs on this relation].", "content": "Excretion of cholesterol with urine was studied using gas chromatography in healthy persons, in patients with cancer of mammary glands, fibroadenoma, lung carcinoma and in patients with beningn processes in lungs. Cholesterol excretion was not increased in patients with the malignant tumors studied. In patients with the cancer of mammary glands and lung carcinoma normal correlation was altered between excretion of cholesterol with urine and content of lipoproteins, protein-bound iodine, 11-hydroxycorticosteroids in blood as well as excretion of cyclic AMP with urine. Treatment with euphylline was accompanied by a decrease in cholesteroluria in patients with fibroadenoma but the drug had no comparable effect on patients with the cancer of mammary glands. In patients with the cancer of mammary glands phenphormine caused distinct decrease and misclerone--moderate increase in excretion of cholesterol with urine.", "contents": "[Relation of urinary excretion of cholesterol in cancer patients to certain hormonal-metabolic parameters and the effect of drugs on this relation]. Excretion of cholesterol with urine was studied using gas chromatography in healthy persons, in patients with cancer of mammary glands, fibroadenoma, lung carcinoma and in patients with beningn processes in lungs. Cholesterol excretion was not increased in patients with the malignant tumors studied. In patients with the cancer of mammary glands and lung carcinoma normal correlation was altered between excretion of cholesterol with urine and content of lipoproteins, protein-bound iodine, 11-hydroxycorticosteroids in blood as well as excretion of cyclic AMP with urine. Treatment with euphylline was accompanied by a decrease in cholesteroluria in patients with fibroadenoma but the drug had no comparable effect on patients with the cancer of mammary glands. In patients with the cancer of mammary glands phenphormine caused distinct decrease and misclerone--moderate increase in excretion of cholesterol with urine."}
{"id": "PMID:220802", "title": "[Study of lipoprotein changes in the vessel wall by ultracentrifugation of aortic extracts in discontinuous density gradients].", "content": "As shown by stepwise density gradient ultracentrifugation, atherogenic lipoproteins pentrating into aorta wall, underwent conversions, which were accompanied by alterations in their hydratation density. The data obtained suggest that complex formation of lipoproteins with components of connective tissue matrix is one of important steps responsible for conversion of atherogenic lipoproteins in vessel wall.", "contents": "[Study of lipoprotein changes in the vessel wall by ultracentrifugation of aortic extracts in discontinuous density gradients]. As shown by stepwise density gradient ultracentrifugation, atherogenic lipoproteins pentrating into aorta wall, underwent conversions, which were accompanied by alterations in their hydratation density. The data obtained suggest that complex formation of lipoproteins with components of connective tissue matrix is one of important steps responsible for conversion of atherogenic lipoproteins in vessel wall."}
{"id": "PMID:220803", "title": "[Change in the apoproteins of very low density lipoproteins in the blood in hypertriglyceridemia].", "content": "Some properties of very low density lipoproteins were studied under conditions causing an increase of their concentration in blood plasma. Content of high molecular apolipoprotein B and low molecular lipoproteins were estimated after fractionation using column chromatography and selective precipitation with tetramethylurea. In 216 men (40-59 years old) with hypertriglyceridemia the increase in content of particles of very low density lipoproteins was accompanied by simultaneous alteration in their composition in blood plasma: content of low molecular polypeptides, triglycerides and cholesterol was increased per a weight unit of apoprotein B. At the same time, the absolute concent of apoprotein B and of low molecular apoproteins of very low density lipoproteins was increased in blood plasma. The most distinct alteration in the ratio of apolipoproteins to very low density lipoproteins was observed, if content of testosterone--activator of lipoprotein lipase--was decreased in blood plasma.", "contents": "[Change in the apoproteins of very low density lipoproteins in the blood in hypertriglyceridemia]. Some properties of very low density lipoproteins were studied under conditions causing an increase of their concentration in blood plasma. Content of high molecular apolipoprotein B and low molecular lipoproteins were estimated after fractionation using column chromatography and selective precipitation with tetramethylurea. In 216 men (40-59 years old) with hypertriglyceridemia the increase in content of particles of very low density lipoproteins was accompanied by simultaneous alteration in their composition in blood plasma: content of low molecular polypeptides, triglycerides and cholesterol was increased per a weight unit of apoprotein B. At the same time, the absolute concent of apoprotein B and of low molecular apoproteins of very low density lipoproteins was increased in blood plasma. The most distinct alteration in the ratio of apolipoproteins to very low density lipoproteins was observed, if content of testosterone--activator of lipoprotein lipase--was decreased in blood plasma."}
{"id": "PMID:220807", "title": "[Hydrocyanic acid content in cerals and cereal products].", "content": "In the above paper for the first time a systematic study of the amount of hydrocyanic acid in grains and cereal products is reported. Among 24 analysed wheat, rye, maize and oats types, the presence of hydrocyanic acid could be identified in 19 cases in their Karyopses. Similar is the result with 28 among 31 analysed cereal products. The content of hydrocyanic acid lies between 0.1 and 45 microgram/100 gr dried mass.", "contents": "[Hydrocyanic acid content in cerals and cereal products]. In the above paper for the first time a systematic study of the amount of hydrocyanic acid in grains and cereal products is reported. Among 24 analysed wheat, rye, maize and oats types, the presence of hydrocyanic acid could be identified in 19 cases in their Karyopses. Similar is the result with 28 among 31 analysed cereal products. The content of hydrocyanic acid lies between 0.1 and 45 microgram/100 gr dried mass."}
{"id": "PMID:220809", "title": "[Hemodynamics in patients suffering from hyperkinetic cardiac syndromes and in normal persons under psychological stress before and after treatment with propranolol (author's transl)].", "content": "In patients with hyperkinetic heart syndrome we found at rest a higher heart rate, a higher stroke volume and a higher cardiac output than in normal volunteers. Therefore blood pressure is high although peripheral resistance is lower than in normals. Similar circulatory differences were found under conditions of mental stress. After beta-adrenergic blockade with 15 mg Propranolol heart rate and cardiac output decrease, whereas peripheral resistance increases. Mean blood pressure thus remains unchanged. Even after beta-adrenergic blockade circulatory differences between normals and patients with hyperkinetic heart syndrome are seen. The possible causes of these differences are discussed.", "contents": "[Hemodynamics in patients suffering from hyperkinetic cardiac syndromes and in normal persons under psychological stress before and after treatment with propranolol (author's transl)]. In patients with hyperkinetic heart syndrome we found at rest a higher heart rate, a higher stroke volume and a higher cardiac output than in normal volunteers. Therefore blood pressure is high although peripheral resistance is lower than in normals. Similar circulatory differences were found under conditions of mental stress. After beta-adrenergic blockade with 15 mg Propranolol heart rate and cardiac output decrease, whereas peripheral resistance increases. Mean blood pressure thus remains unchanged. Even after beta-adrenergic blockade circulatory differences between normals and patients with hyperkinetic heart syndrome are seen. The possible causes of these differences are discussed."}
{"id": "PMID:220806", "title": "Feline preleukemia: an animal model of human disease.", "content": "In man, hematologic abnormalities precede the development of acute myeloblastic leukemia in about one-third of individuals. This preleukemic state may represent a stage of adult leukemia wherein small numbers of leukemic cells are present and the normal marrow stem cell compartment has not been seriously compromised. A syndrome resembling human preleukemia occurs in cats infected with feline leukemia virus (FeLV). This disorder is characterized by anemia, leukopenia or thrombocytopenia occurring weeks or months prior to the development of feline acute leukemia. The natural occurrence of this syndrome in this domestic animal population makes it a potential model of human preleukemia. Initial poor results of therapy of human preleukemia presently prohibit one from carrying out controlled trials with chemotherapeutic agents in such a group of patients. Preliminary trials with chemo- and/or immunotherapy may be more easily attempted with FeLV infected preleukemic cats.", "contents": "Feline preleukemia: an animal model of human disease. In man, hematologic abnormalities precede the development of acute myeloblastic leukemia in about one-third of individuals. This preleukemic state may represent a stage of adult leukemia wherein small numbers of leukemic cells are present and the normal marrow stem cell compartment has not been seriously compromised. A syndrome resembling human preleukemia occurs in cats infected with feline leukemia virus (FeLV). This disorder is characterized by anemia, leukopenia or thrombocytopenia occurring weeks or months prior to the development of feline acute leukemia. The natural occurrence of this syndrome in this domestic animal population makes it a potential model of human preleukemia. Initial poor results of therapy of human preleukemia presently prohibit one from carrying out controlled trials with chemotherapeutic agents in such a group of patients. Preliminary trials with chemo- and/or immunotherapy may be more easily attempted with FeLV infected preleukemic cats."}
{"id": "PMID:220810", "title": "[Attempts to enrich and to solubilize the muscarinic acetylcholinereceptor from bovine caudate nucleus (author's transl)].", "content": "Neuronal membranes of postsynaptic origin twofold enriched in acetylcholinesterase, muscarinic acetylcholinereceptor and (Na+/K+)-ATP-Phosphohydrolase, proteins associated with cholinergic nerve excitability, were prepared with yields between 60 and 75% from bovine caudate nucleus. On subfractionation of these membranes an additional twofold enrichment of the mentioned proteins is achieved in different subfractions. SDS-gradient gel electrophoresis shows that these subfractions have slightly different polypeptide compositions. Neuronal membranes of presynaptic origin on the other hand, prepared from purified synaptosomes, possess only small amounts of the mentioned proteins, showing no enrichment with respect to the homogenate. Solubilization of acetylcholinesterase with 1 M NaC1 as well as of muscarinic acetylcholinreceptor with 2 M NaC1 does not succeed. These proteins are therefore not solely bound by ionic forces to the isolated membranes from bovine caudate nucleus.", "contents": "[Attempts to enrich and to solubilize the muscarinic acetylcholinereceptor from bovine caudate nucleus (author's transl)]. Neuronal membranes of postsynaptic origin twofold enriched in acetylcholinesterase, muscarinic acetylcholinereceptor and (Na+/K+)-ATP-Phosphohydrolase, proteins associated with cholinergic nerve excitability, were prepared with yields between 60 and 75% from bovine caudate nucleus. On subfractionation of these membranes an additional twofold enrichment of the mentioned proteins is achieved in different subfractions. SDS-gradient gel electrophoresis shows that these subfractions have slightly different polypeptide compositions. Neuronal membranes of presynaptic origin on the other hand, prepared from purified synaptosomes, possess only small amounts of the mentioned proteins, showing no enrichment with respect to the homogenate. Solubilization of acetylcholinesterase with 1 M NaC1 as well as of muscarinic acetylcholinreceptor with 2 M NaC1 does not succeed. These proteins are therefore not solely bound by ionic forces to the isolated membranes from bovine caudate nucleus."}
{"id": "PMID:220814", "title": "Antibody studies in the Kuru region. Immunological epidemiology of population groups in and adjacent to the Kuru region in Papua New Guinea. I. Enteroviruses.", "content": "A serological survey is reported for antibodies to Coxsackie, ECHO and polioviruses on sera collected in the kuru region of Papua New Guinea during earliest European contacts with kuru-affected and control populations through the period of highest kuru incidence. The results are discussed in the light of increasing European contact over the period of investigation. Suggestions are made concerning possible immunization programs with polioviruses.", "contents": "Antibody studies in the Kuru region. Immunological epidemiology of population groups in and adjacent to the Kuru region in Papua New Guinea. I. Enteroviruses. A serological survey is reported for antibodies to Coxsackie, ECHO and polioviruses on sera collected in the kuru region of Papua New Guinea during earliest European contacts with kuru-affected and control populations through the period of highest kuru incidence. The results are discussed in the light of increasing European contact over the period of investigation. Suggestions are made concerning possible immunization programs with polioviruses."}
{"id": "PMID:220822", "title": "[Pathogenesis of several forms of progressive muscular dystrophy].", "content": "The level of cyclic 3,5-adenosine monophosphate (cAMP), the activity of adenylate cyclase (AC) and phosphodiesterase (PDE) were studied in bioptates of the muscles of 17 patients with different forms of myopathy. The cAMP level and AC activity were decreased while that of PDE was increased. These changes are particularly demonstrative in patients with Erba type of myopathy. It is recommended that beta-adrenomimetic drugs and PDE inhibitors may be tried in pathogenetic therapy.", "contents": "[Pathogenesis of several forms of progressive muscular dystrophy]. The level of cyclic 3,5-adenosine monophosphate (cAMP), the activity of adenylate cyclase (AC) and phosphodiesterase (PDE) were studied in bioptates of the muscles of 17 patients with different forms of myopathy. The cAMP level and AC activity were decreased while that of PDE was increased. These changes are particularly demonstrative in patients with Erba type of myopathy. It is recommended that beta-adrenomimetic drugs and PDE inhibitors may be tried in pathogenetic therapy."}
{"id": "PMID:220823", "title": "[Pathogenetic therapy of nervous system and muscular diseases using large doses of prednisolone on alternate days].", "content": "A total of 230 patients with myasthenia, polymositis, disseminated sclerosis and myeloradiculopolyneuronitis were administered high doses of prednisolone (up to 100 mg) every other day. The treatment efficacy and low incidence of side effects and complications are emphasized. High doses of prednisolone given every other day do not inhibit secretions of endogenic ACTH and cortisol. The immunodepressant effect of the drug remains unchanged.", "contents": "[Pathogenetic therapy of nervous system and muscular diseases using large doses of prednisolone on alternate days]. A total of 230 patients with myasthenia, polymositis, disseminated sclerosis and myeloradiculopolyneuronitis were administered high doses of prednisolone (up to 100 mg) every other day. The treatment efficacy and low incidence of side effects and complications are emphasized. High doses of prednisolone given every other day do not inhibit secretions of endogenic ACTH and cortisol. The immunodepressant effect of the drug remains unchanged."}
{"id": "PMID:220825", "title": "[Clinical value of studying strength-duration curves using intramuscular (needle) electrodes in patients with lumbosacral radicular syndromes].", "content": "The paper deals with the results of a force-duration curve comparative study which was accomplished-in 20 patients with the aid of usual skin and acupunctural point electrodes. The spicular needle introduced painlessly into the muscles studied, served as an active electrode connected by a fine cord to a clamp of the electric pulser. In order to determine the force-duration curve, 10 rectangular impulses of a different length at a constant frequency of 1 hz were used. The results demonstrated that the determination of the force-duration curve with the aid of acupuncture is a more sensitive and precise method of study inasmuch as it permits to receive genuine values of the current in the test area.", "contents": "[Clinical value of studying strength-duration curves using intramuscular (needle) electrodes in patients with lumbosacral radicular syndromes]. The paper deals with the results of a force-duration curve comparative study which was accomplished-in 20 patients with the aid of usual skin and acupunctural point electrodes. The spicular needle introduced painlessly into the muscles studied, served as an active electrode connected by a fine cord to a clamp of the electric pulser. In order to determine the force-duration curve, 10 rectangular impulses of a different length at a constant frequency of 1 hz were used. The results demonstrated that the determination of the force-duration curve with the aid of acupuncture is a more sensitive and precise method of study inasmuch as it permits to receive genuine values of the current in the test area."}
{"id": "PMID:220826", "title": "[Facial autonomic and trophic disorders].", "content": "The paper is concerned with the results of a clinical electrophysiological, biochemical, histochemical, X-ray and morphological study of 289 patients with different vegetovascular and trophical disturbances, mainly of a regional character, in the facial area. Some clinical aspects and questions of the pathogenesis of these disturbances are discussed which are not sufficiently reflected in the literature. It is suggested that the form of the pterygopalatine ganglion is related to the incidence of the pathological process and the traits of vegetative and pain phenomena, accompanying the Sluder syndrome. Vegetovascular changes were revealed in the skin of the face and enzymatic changes in mucous membrane of the nose on the homolateral to the paresis side of the face in lesions of the facial nerve. Specific vegetative trophical changes were also found in a progressive hemiatrophy of the face, Barrakera-Simons disease, in the syndrome of facial hemistrophy due to lesions of the different vegetative and somatic structures of the nervous system.", "contents": "[Facial autonomic and trophic disorders]. The paper is concerned with the results of a clinical electrophysiological, biochemical, histochemical, X-ray and morphological study of 289 patients with different vegetovascular and trophical disturbances, mainly of a regional character, in the facial area. Some clinical aspects and questions of the pathogenesis of these disturbances are discussed which are not sufficiently reflected in the literature. It is suggested that the form of the pterygopalatine ganglion is related to the incidence of the pathological process and the traits of vegetative and pain phenomena, accompanying the Sluder syndrome. Vegetovascular changes were revealed in the skin of the face and enzymatic changes in mucous membrane of the nose on the homolateral to the paresis side of the face in lesions of the facial nerve. Specific vegetative trophical changes were also found in a progressive hemiatrophy of the face, Barrakera-Simons disease, in the syndrome of facial hemistrophy due to lesions of the different vegetative and somatic structures of the nervous system."}
{"id": "PMID:220829", "title": "Interaction of metal ions with nucleic acids. Interaction of copper(II) with adenosine and its derivatives.", "content": "The interaction of copper(II) with adenosine, 2'-deoxyadenosine, 1-methyladenosine, 7-deazaadenosine and AMP was studied by spectroscopic and magnetochemical methods. In non-aqueous medium, copper(II) interacts with adenosine and AMP at N-7 and N-1, and with 1-methyladenosine at N-7 and N-3. The copper ion is not bound to the NH2 group. In aqueous solution, copper(II) interacts both with N-7 and N-1 of adenosine, and in AMP additionally with the phosphate group. The interaction of copper(II) with the heterocyclic part, but not withthe phosphate group, is dependent on the extent of protonation of the molecular. A crystalline AMP-copper(II) complex [Cu(C10H12N5O7P).(H2O)2] was obtained; the phosphate group and probably N-7 are involved in the complex formation.", "contents": "Interaction of metal ions with nucleic acids. Interaction of copper(II) with adenosine and its derivatives. The interaction of copper(II) with adenosine, 2'-deoxyadenosine, 1-methyladenosine, 7-deazaadenosine and AMP was studied by spectroscopic and magnetochemical methods. In non-aqueous medium, copper(II) interacts with adenosine and AMP at N-7 and N-1, and with 1-methyladenosine at N-7 and N-3. The copper ion is not bound to the NH2 group. In aqueous solution, copper(II) interacts both with N-7 and N-1 of adenosine, and in AMP additionally with the phosphate group. The interaction of copper(II) with the heterocyclic part, but not withthe phosphate group, is dependent on the extent of protonation of the molecular. A crystalline AMP-copper(II) complex [Cu(C10H12N5O7P).(H2O)2] was obtained; the phosphate group and probably N-7 are involved in the complex formation."}
{"id": "PMID:220830", "title": "Studies on the structure of haptoglobin and the haptoglobin-haemoglobin complex by spin and fluorescence labelling.", "content": "Human haptoglobin (Hp) of the 1-1 type incorporated one spin or fluorescence marker per molecule; the markers were found in the beta chain. Formation of the complex between spin-labelled Hp and haemoglobin or antibody caused conformational changes in the Hp molecular, evidenced by increased participation in the electron paramagnetic resonance spectrum of the component bound with the slowly rotating marker. From fluorescence-labelled Hp, the beta chain was isolated and cleaved by CNBr; only in one of the obtained peptides, one out of 4 histidine residues was modified with the marker.", "contents": "Studies on the structure of haptoglobin and the haptoglobin-haemoglobin complex by spin and fluorescence labelling. Human haptoglobin (Hp) of the 1-1 type incorporated one spin or fluorescence marker per molecule; the markers were found in the beta chain. Formation of the complex between spin-labelled Hp and haemoglobin or antibody caused conformational changes in the Hp molecular, evidenced by increased participation in the electron paramagnetic resonance spectrum of the component bound with the slowly rotating marker. From fluorescence-labelled Hp, the beta chain was isolated and cleaved by CNBr; only in one of the obtained peptides, one out of 4 histidine residues was modified with the marker."}
{"id": "PMID:220831", "title": "The effect of sialic acid on adenylate cyclase activity and thyrotropin-receptor binding in human thyroid membranes.", "content": "Exogenous sialic acid at 3 mM and higher concentrations inhibits the basal adenylate cyclase activity and the activity stimulated by thyrotropin (TSH) and fluoride in the human thyroid membrane fraction; 30 mM-sialic acid acts as an inhibitor of TSH binding. The decrease of these activities at high sialic acid concentrations might be ascribed to changes in membrane conformation caused by acidic character of this sugar.", "contents": "The effect of sialic acid on adenylate cyclase activity and thyrotropin-receptor binding in human thyroid membranes. Exogenous sialic acid at 3 mM and higher concentrations inhibits the basal adenylate cyclase activity and the activity stimulated by thyrotropin (TSH) and fluoride in the human thyroid membrane fraction; 30 mM-sialic acid acts as an inhibitor of TSH binding. The decrease of these activities at high sialic acid concentrations might be ascribed to changes in membrane conformation caused by acidic character of this sugar."}
{"id": "PMID:220828", "title": "[Role of the pituitary-adrenal system in the pathogenesis of severe closed craniocerebral injuries].", "content": "In patients with severe contusion of the brain, the concentration of ACTH in blood increases from the 2nd and to the 10th day after the trauma whereas the level of 11-OCS remains on a significantly high level during the entire period of treatment. The potential reserves of the adrenal cortex are reduced on the 5th day. The ACTH level returns to normal by the end of the 3rd week. Neurohormonal shifts play an important role in the pathogenesis of the trauma and cause the development of its clinical manifestations.", "contents": "[Role of the pituitary-adrenal system in the pathogenesis of severe closed craniocerebral injuries]. In patients with severe contusion of the brain, the concentration of ACTH in blood increases from the 2nd and to the 10th day after the trauma whereas the level of 11-OCS remains on a significantly high level during the entire period of treatment. The potential reserves of the adrenal cortex are reduced on the 5th day. The ACTH level returns to normal by the end of the 3rd week. Neurohormonal shifts play an important role in the pathogenesis of the trauma and cause the development of its clinical manifestations."}
{"id": "PMID:220832", "title": "Effects of soluble fractions from untreated and SiO2-treated subcellular particles of macrophages on nucleic acid metabolism in isolated nuclei of experimental granulation tissue.", "content": "Nuclei isolated from proliferating granulation tissue were incubated with 20 000 g supernatants from untreated and SiO2-treated subcellular particles of rat peritoneal macrophages in the presence of radioactive nucleic acid precursors. The supernatant from SiO2-treated subcellular particles increased the incorporation of [3H]CTP into nuclear RNA maximally by 26% at 5 min, and that of [methyl-3H]dTTP into DNA by 16% at 20 min. The release of radioactivity from labeled DNA was suppressed simultaneously. An RNase preparation from rat peritoneal macrophages enhanced the release of radioactivity from labeled DNA similarly as the soluble fraction from untreated subcellular particles of macrophages. The results suggest that the effects of the soluble fractions upon DNA metabolism of granuloma cells are at least partly independent of the effects on RNA metabolism and that the soluble fraction from SiO2-treated subcellular particles of macrophages stabilizes DNA through inhibition of nuclease activity.", "contents": "Effects of soluble fractions from untreated and SiO2-treated subcellular particles of macrophages on nucleic acid metabolism in isolated nuclei of experimental granulation tissue. Nuclei isolated from proliferating granulation tissue were incubated with 20 000 g supernatants from untreated and SiO2-treated subcellular particles of rat peritoneal macrophages in the presence of radioactive nucleic acid precursors. The supernatant from SiO2-treated subcellular particles increased the incorporation of [3H]CTP into nuclear RNA maximally by 26% at 5 min, and that of [methyl-3H]dTTP into DNA by 16% at 20 min. The release of radioactivity from labeled DNA was suppressed simultaneously. An RNase preparation from rat peritoneal macrophages enhanced the release of radioactivity from labeled DNA similarly as the soluble fraction from untreated subcellular particles of macrophages. The results suggest that the effects of the soluble fractions upon DNA metabolism of granuloma cells are at least partly independent of the effects on RNA metabolism and that the soluble fraction from SiO2-treated subcellular particles of macrophages stabilizes DNA through inhibition of nuclease activity."}
{"id": "PMID:220834", "title": "Demyelinating encephalomyelitis induced by a long-term corona virus infection in rats. A preliminary report.", "content": "About 30% of weanling rats inoculated with JHM virus developed a subacute demyelinating encephalomyelitis (SDE) 3 weeks after inoculation (a.i.). From the remaining animals, 5% displayed overt neurological signs 3, 6, and 8 months a.i. Animals with and without clinical signs 6-8 months a.i. were morphologically examined. Fresh demyelinating lesions could be demonstrated in paralyzed animals. Viral antigen was demonstrated and infectious JHM virus could be recovered from one animal which developed clinical signs at 3 months a.i. In one animal with clinical onset of 8 months a.i. completely remyelinated areas as well as recent demyelinating lesions were observed, suggesting a recurrence of the disease process. Remyelinated areas were also found in 40% of clinically silent animals. The morphology of the late onset of the demyelination was similar to that occurring in SDE. Remyelination consisted of both CNS and PNS-type. This animal model offers the possibility to investigate the virus-host relationship which is responsible for the induction of a demyelinating process after a long incubation period.", "contents": "Demyelinating encephalomyelitis induced by a long-term corona virus infection in rats. A preliminary report. About 30% of weanling rats inoculated with JHM virus developed a subacute demyelinating encephalomyelitis (SDE) 3 weeks after inoculation (a.i.). From the remaining animals, 5% displayed overt neurological signs 3, 6, and 8 months a.i. Animals with and without clinical signs 6-8 months a.i. were morphologically examined. Fresh demyelinating lesions could be demonstrated in paralyzed animals. Viral antigen was demonstrated and infectious JHM virus could be recovered from one animal which developed clinical signs at 3 months a.i. In one animal with clinical onset of 8 months a.i. completely remyelinated areas as well as recent demyelinating lesions were observed, suggesting a recurrence of the disease process. Remyelinated areas were also found in 40% of clinically silent animals. The morphology of the late onset of the demyelination was similar to that occurring in SDE. Remyelination consisted of both CNS and PNS-type. This animal model offers the possibility to investigate the virus-host relationship which is responsible for the induction of a demyelinating process after a long incubation period."}
{"id": "PMID:220835", "title": "Experimental aggression and bruxism in rats.", "content": "Aggression has been suggested as one of the etiologic factors in bruxism. Experimental bruxism, audible, nonfunctional grinding or clenching of the teeth, was provoked in aggressive animals by drugs affecting central dopaminergic systems. Electric foot-stimulation was used to induce aggression, evident as the threatening or fighting position, in paired male Wistar rats. After initial stimulation, shocks were given only to maintain the characteristic fighting pose. Apomorphine facilitated induction of aggressive behaviour by electric shocks, and the rats receiving both treatments showed bruxism more frequently than controls subjected to shocks alone: up to 95 bruxism periods registered by a tape recorder during 30 min, as opposed to a few sporadic periods in the controls. Without shocks, apomorphine-treated rats displayed stereotypy with locomotion and biting of various objects. Aggression and bruxism were not equally successfully induced after L-dopa given with a peripheral inhibitor of aromatic amino acid decarboxylase (benserazide) or when L-dopa treatment was modified with the inhibitor of dopamine-beta-hydroxylase (diethyldithiocarbamate) or monoamine oxidase inhibitor (iproniazid). However, all the present drug combinations known to enhance central dopaminergic function seemed to increase irritability and disposition to experimental oral dyskinesias. This was observed especially when a sensory stimulus was applied at the same time or the drug had an amine-releasing effect (pheniprazine).", "contents": "Experimental aggression and bruxism in rats. Aggression has been suggested as one of the etiologic factors in bruxism. Experimental bruxism, audible, nonfunctional grinding or clenching of the teeth, was provoked in aggressive animals by drugs affecting central dopaminergic systems. Electric foot-stimulation was used to induce aggression, evident as the threatening or fighting position, in paired male Wistar rats. After initial stimulation, shocks were given only to maintain the characteristic fighting pose. Apomorphine facilitated induction of aggressive behaviour by electric shocks, and the rats receiving both treatments showed bruxism more frequently than controls subjected to shocks alone: up to 95 bruxism periods registered by a tape recorder during 30 min, as opposed to a few sporadic periods in the controls. Without shocks, apomorphine-treated rats displayed stereotypy with locomotion and biting of various objects. Aggression and bruxism were not equally successfully induced after L-dopa given with a peripheral inhibitor of aromatic amino acid decarboxylase (benserazide) or when L-dopa treatment was modified with the inhibitor of dopamine-beta-hydroxylase (diethyldithiocarbamate) or monoamine oxidase inhibitor (iproniazid). However, all the present drug combinations known to enhance central dopaminergic function seemed to increase irritability and disposition to experimental oral dyskinesias. This was observed especially when a sensory stimulus was applied at the same time or the drug had an amine-releasing effect (pheniprazine)."}
{"id": "PMID:220837", "title": "A prospective study on the incidence and significance of congenital cytomegalovirus infection.", "content": "Screening of 3060 neonates for congenital cytomegalovirus (CMV) infection by virus excretion in the urine showed an overall incidence of 0.4%. The incidence was about 1% for mothers between 16 and 25 years and only 0.2% for mothers between 25 and 35. No mothers over 35 years of age gave birth to congenitally infected infants. The percentage of women in the child-bearing age susceptible to CMV infection was estimated by the absence of CMV complement-fixing antibodies in cord sera and ranged from 48% to 33% with increasing age. None of the infected infants showed obvious signs of congenital CMV infection at birth. At follow-up, two infants showed slight, but transient symptoms compatible with a foetal infection; a pair of premature twins exhibited retarded physical and psychomotor development, but this could just as well be ascribed to the prematurity itself. None of the infants had detectable CMV--IgM antibodies in cord sera, but a trend towards elevated total IgM concentration in cord sera and elevated virus excretion titres appeared in the infants with symptoms. With the very low incidence and no signs of sensomotor sequelae the preliminary conclusion is that foetal CMV infection in our population by no means has a significance to deserve screening or a vaccination programme.", "contents": "A prospective study on the incidence and significance of congenital cytomegalovirus infection. Screening of 3060 neonates for congenital cytomegalovirus (CMV) infection by virus excretion in the urine showed an overall incidence of 0.4%. The incidence was about 1% for mothers between 16 and 25 years and only 0.2% for mothers between 25 and 35. No mothers over 35 years of age gave birth to congenitally infected infants. The percentage of women in the child-bearing age susceptible to CMV infection was estimated by the absence of CMV complement-fixing antibodies in cord sera and ranged from 48% to 33% with increasing age. None of the infected infants showed obvious signs of congenital CMV infection at birth. At follow-up, two infants showed slight, but transient symptoms compatible with a foetal infection; a pair of premature twins exhibited retarded physical and psychomotor development, but this could just as well be ascribed to the prematurity itself. None of the infants had detectable CMV--IgM antibodies in cord sera, but a trend towards elevated total IgM concentration in cord sera and elevated virus excretion titres appeared in the infants with symptoms. With the very low incidence and no signs of sensomotor sequelae the preliminary conclusion is that foetal CMV infection in our population by no means has a significance to deserve screening or a vaccination programme."}
{"id": "PMID:220838", "title": "Screening of cord blood low-density-lipoprotein cholesterol in the diagnosis of familial hypercholesterolaemia: a study of 2000 infants.", "content": "A prospective follow-up study of infants selected by cord blood total cholesterol (TC) and low-density-lipoprotein cholesterol (LDL-C) levels from 2000 consecutive live births was undertaken to reassess the role of cord blood screening in the diagnosis of familial hypercholesterolaemia (FH). Mean values for serum cholesterol were (mmol/l +/- S.D.): TC, 1.83 +/- 0.56; LDL-C, 0.90 +/- 0.49; HDL-C, 0.70 +/- 0.33; TG, 0.38 +/- 0.16. Seventy-three of 117 infants who had had a cord TC and/or LDL-C greater than 95th percentile, and 373 control group children (cord TC and/or LDL-C less than 95th percentile) were followed up at age 3--12 months. Six of the 117 were hypercholesterolaemic (HC), and one child had an HC parent: positive detection rate greater than or equal to 0.05%; false positive rate greater than or equal to 3.7%. Four control-group children were HC and had an HC parent; false negative rate greater than or equal to 1.1%. With the possible exception of detecting FH in a child with a known affected parent, cord blood screening appears to be unreliable for the diagnosis of FH.", "contents": "Screening of cord blood low-density-lipoprotein cholesterol in the diagnosis of familial hypercholesterolaemia: a study of 2000 infants. A prospective follow-up study of infants selected by cord blood total cholesterol (TC) and low-density-lipoprotein cholesterol (LDL-C) levels from 2000 consecutive live births was undertaken to reassess the role of cord blood screening in the diagnosis of familial hypercholesterolaemia (FH). Mean values for serum cholesterol were (mmol/l +/- S.D.): TC, 1.83 +/- 0.56; LDL-C, 0.90 +/- 0.49; HDL-C, 0.70 +/- 0.33; TG, 0.38 +/- 0.16. Seventy-three of 117 infants who had had a cord TC and/or LDL-C greater than 95th percentile, and 373 control group children (cord TC and/or LDL-C less than 95th percentile) were followed up at age 3--12 months. Six of the 117 were hypercholesterolaemic (HC), and one child had an HC parent: positive detection rate greater than or equal to 0.05%; false positive rate greater than or equal to 3.7%. Four control-group children were HC and had an HC parent; false negative rate greater than or equal to 1.1%. With the possible exception of detecting FH in a child with a known affected parent, cord blood screening appears to be unreliable for the diagnosis of FH."}
{"id": "PMID:220839", "title": "Multiple pituitary hormone deficiencies in eight siblings of one Jewish Moroccan family.", "content": "In a Jewish Moroccan inbred family, 8 of 12 siblings were found to have multiple deficiencies of pituitary hormones, including GH, TSH and gonadotrophins. The parents showed no deficiency and are in good health, as are the other 4 siblings. The investigations carried out indicate that in this family the etiology is hereditary in nature, probably being autosomal recessive, with the defect located in the pituitary gland.", "contents": "Multiple pituitary hormone deficiencies in eight siblings of one Jewish Moroccan family. In a Jewish Moroccan inbred family, 8 of 12 siblings were found to have multiple deficiencies of pituitary hormones, including GH, TSH and gonadotrophins. The parents showed no deficiency and are in good health, as are the other 4 siblings. The investigations carried out indicate that in this family the etiology is hereditary in nature, probably being autosomal recessive, with the defect located in the pituitary gland."}
{"id": "PMID:220836", "title": "Distribution of cyclic nucleotides in the organ of Corti.", "content": "Recent developments in radioimmunoassay technology have made possible measurements of cyclic nucleotides in individual specimens of the organ of Corti and its subdivisions. Steep longitudinal and transverse gradients of glycogen are known to exist in the organ of Corti of the guinea pig, with preferential accumulation in the outer hair cells of the apical turns. However, no significant longitudinal gradient of cyclic AMP was detectable in the organ of Corti, and the concentration of the compound was found to be nearly equal in the inner and outer hair cell layers. This is indirect evidence against the concept that cyclic AMP plays a role as \"second messenger\" in the control of glycogen metabolism of the organ of Corti. By contrast, the concentration of cyclic GMP was found to be consistently higher in the inner layer than in the outer layer of the organ of Corti, and to increase significantly in basal direction. This trend is remarkably similar to the distribution patterns of acetylcholinesterase, which may be considered as indirect evidence in favor of a possible role of cyclic GMP in the mediation of cholinergic effects.", "contents": "Distribution of cyclic nucleotides in the organ of Corti. Recent developments in radioimmunoassay technology have made possible measurements of cyclic nucleotides in individual specimens of the organ of Corti and its subdivisions. Steep longitudinal and transverse gradients of glycogen are known to exist in the organ of Corti of the guinea pig, with preferential accumulation in the outer hair cells of the apical turns. However, no significant longitudinal gradient of cyclic AMP was detectable in the organ of Corti, and the concentration of the compound was found to be nearly equal in the inner and outer hair cell layers. This is indirect evidence against the concept that cyclic AMP plays a role as \"second messenger\" in the control of glycogen metabolism of the organ of Corti. By contrast, the concentration of cyclic GMP was found to be consistently higher in the inner layer than in the outer layer of the organ of Corti, and to increase significantly in basal direction. This trend is remarkably similar to the distribution patterns of acetylcholinesterase, which may be considered as indirect evidence in favor of a possible role of cyclic GMP in the mediation of cholinergic effects."}
{"id": "PMID:220840", "title": "Lymphocyte blast transformation response of seropositive and seronegative subjects to herpes simplex, rubella, mumps and measles virus antigens.", "content": "Lymphocytes from seronegative and seropositive subjects were stimulated in vitro with herpes simplex, rubella, mumps and measles viral antigens. Viral antigens were beta-propiolactone inactivated crude material (containing cell-membrane fragments) grown in Vero cells and prepared identically. Lymphocytes from seropositive subjects responded specifically to herpes virus antigen, and most rubella and mumps seropositive subjects responded to the respective antigens. Measles antigen, however, did not stimulate lymphocytes from seropositive or seronegative subjects. The responses of three subjects studied repeatedly over a period of several weeks were reproducible. The results of the study support the usefulness of the blast transformation test as a measure of sensitization to viruses.", "contents": "Lymphocyte blast transformation response of seropositive and seronegative subjects to herpes simplex, rubella, mumps and measles virus antigens. Lymphocytes from seronegative and seropositive subjects were stimulated in vitro with herpes simplex, rubella, mumps and measles viral antigens. Viral antigens were beta-propiolactone inactivated crude material (containing cell-membrane fragments) grown in Vero cells and prepared identically. Lymphocytes from seropositive subjects responded specifically to herpes virus antigen, and most rubella and mumps seropositive subjects responded to the respective antigens. Measles antigen, however, did not stimulate lymphocytes from seropositive or seronegative subjects. The responses of three subjects studied repeatedly over a period of several weeks were reproducible. The results of the study support the usefulness of the blast transformation test as a measure of sensitization to viruses."}
{"id": "PMID:220843", "title": "Apomorphine stereotypies and transmitter mechanisms in the striatum. I. Changes in the apomorphine stereotypies caused by drugs acting on the GABA-ergic, dopaminergic and cholinergic transmission.", "content": "Experiments on male albino mice were carried out in order to determine the effects of drugs connecting with the GABA-ergic, dopaminergic and cholinergic transmission, on apomorphine stereotypies. The agents acting on GABA-ergic transmission are found to reduce the intensity of apomorphine stereotypies in the following order (arranged from strongest to weakest effect and expressed in doses of microgram per mouse: GABA (100), aminooxyacetic acid (5), diazepam (20), picrotoxin (1), GABA (10), semicarbazide (30), picrotoxin (0.1). The agents acting on the dopaminergic transmission also reduce apomorphine stereotypies in the following order: haloperidol (20;2), L-DOPA (500 mg/kg, i. p.), alpha-methylparatyrosine (150 mg/kg, i. p.) diethyldithiocarbamate (200). The strongest antagonistic effect in the two groups of agents studied was found for haloperidol. The agents acting on the cholinergic transmission (agonists and antagonists of muscarinic and nicotinic cholinoreceptors) have no significant effect on apomorphine stereotypies. It is assumed that the striatum is not the only brain structure responsible for apomorphine stereotypies.", "contents": "Apomorphine stereotypies and transmitter mechanisms in the striatum. I. Changes in the apomorphine stereotypies caused by drugs acting on the GABA-ergic, dopaminergic and cholinergic transmission. Experiments on male albino mice were carried out in order to determine the effects of drugs connecting with the GABA-ergic, dopaminergic and cholinergic transmission, on apomorphine stereotypies. The agents acting on GABA-ergic transmission are found to reduce the intensity of apomorphine stereotypies in the following order (arranged from strongest to weakest effect and expressed in doses of microgram per mouse: GABA (100), aminooxyacetic acid (5), diazepam (20), picrotoxin (1), GABA (10), semicarbazide (30), picrotoxin (0.1). The agents acting on the dopaminergic transmission also reduce apomorphine stereotypies in the following order: haloperidol (20;2), L-DOPA (500 mg/kg, i. p.), alpha-methylparatyrosine (150 mg/kg, i. p.) diethyldithiocarbamate (200). The strongest antagonistic effect in the two groups of agents studied was found for haloperidol. The agents acting on the cholinergic transmission (agonists and antagonists of muscarinic and nicotinic cholinoreceptors) have no significant effect on apomorphine stereotypies. It is assumed that the striatum is not the only brain structure responsible for apomorphine stereotypies."}
{"id": "PMID:220844", "title": "Apomorphine stereotypies and transmitter mechanisms in the striatum. II. Interactions between GABA-ergic and cholinergic transmission.", "content": "The interactions between the GABA-ergic and cholinergic transmissions in the striatum of male mice are determined through microinjection in the striatum of agents influencing these types of transmission in cases of apomorphine stereotypies. It is found that the agents acting on the cholinergic transmission (agonists and antagonists of the muscarinic and nicotinic cholinoreceptors), antagonize considerably the reducing effect on apomorphine stereotypies of the agents acting on GABA-ergic transmission. Conversely, the agents acting on GABA-ergic transmission (pre- and post-synaptic) intensify or weaken the effects of the agents acting on the cholinergic transmission with respect to apomorphine stereotypies, though the difference is not entirely significant. The influence of the effects of the agents acting on the GABA-ergic transmission in cases of apomorphine stereotypies is thought to be due to the antagonistic action of the striatal cholinergic neurones on the GABA-ergic neurones, while the latter interact with the striatal dopaminergic neurones either directly or through the mediation of substantia nigra. The lack of direct interactions between the GABA-ergic and the cholinergic neurones in the striatum explains the weak influence on cholinergic transmission exerted by the agents acting on the GABA-ergic transmission with respect to apomorphine stereotypies.", "contents": "Apomorphine stereotypies and transmitter mechanisms in the striatum. II. Interactions between GABA-ergic and cholinergic transmission. The interactions between the GABA-ergic and cholinergic transmissions in the striatum of male mice are determined through microinjection in the striatum of agents influencing these types of transmission in cases of apomorphine stereotypies. It is found that the agents acting on the cholinergic transmission (agonists and antagonists of the muscarinic and nicotinic cholinoreceptors), antagonize considerably the reducing effect on apomorphine stereotypies of the agents acting on GABA-ergic transmission. Conversely, the agents acting on GABA-ergic transmission (pre- and post-synaptic) intensify or weaken the effects of the agents acting on the cholinergic transmission with respect to apomorphine stereotypies, though the difference is not entirely significant. The influence of the effects of the agents acting on the GABA-ergic transmission in cases of apomorphine stereotypies is thought to be due to the antagonistic action of the striatal cholinergic neurones on the GABA-ergic neurones, while the latter interact with the striatal dopaminergic neurones either directly or through the mediation of substantia nigra. The lack of direct interactions between the GABA-ergic and the cholinergic neurones in the striatum explains the weak influence on cholinergic transmission exerted by the agents acting on the GABA-ergic transmission with respect to apomorphine stereotypies."}
{"id": "PMID:220845", "title": "Uptake and release of adenosine in isolated rat fat cells.", "content": "Radioactively labelled adenosine and adenine were rapidly taken up by isolated rat fat cells, and incorporated into nucleotides, of which ATP dominated. The overall process had an apparent Km of 1--5 micrometers. During incubation, especially in the presence of lipolytic agents, there was a reduction in labelled ATP with a compensatory increase in ADP, AMP, cAMP and nucleosides. The build-up of adenosine during incubation was inhibited by theophylline, which inhibits 5'-nucleotidase. Radioactivity released from perifused fat cells consisted mainly of nucleoside material, of which adenosine predominated. Lipolytic stimulation caused no significant increase in nucleoside outflow from perifused cells, whereas oxygenation was capable of reducing this outflow. It is concluded that adenosine is formed by fat cells as a consequence of ATP breakdown. Stimulation of lipolysis during activation of the sympathetic nerves leads to reversible ATP breakdown and adenosine release. Adenosine might therefore act as a modulator of lipolysis in vivo under these conditions, even though it does not serve as a feed back regulator in the proper sense.", "contents": "Uptake and release of adenosine in isolated rat fat cells. Radioactively labelled adenosine and adenine were rapidly taken up by isolated rat fat cells, and incorporated into nucleotides, of which ATP dominated. The overall process had an apparent Km of 1--5 micrometers. During incubation, especially in the presence of lipolytic agents, there was a reduction in labelled ATP with a compensatory increase in ADP, AMP, cAMP and nucleosides. The build-up of adenosine during incubation was inhibited by theophylline, which inhibits 5'-nucleotidase. Radioactivity released from perifused fat cells consisted mainly of nucleoside material, of which adenosine predominated. Lipolytic stimulation caused no significant increase in nucleoside outflow from perifused cells, whereas oxygenation was capable of reducing this outflow. It is concluded that adenosine is formed by fat cells as a consequence of ATP breakdown. Stimulation of lipolysis during activation of the sympathetic nerves leads to reversible ATP breakdown and adenosine release. Adenosine might therefore act as a modulator of lipolysis in vivo under these conditions, even though it does not serve as a feed back regulator in the proper sense."}
{"id": "PMID:220846", "title": "Biochemical and morphological study on hepatotoxicity of azathioprine in rat.", "content": "Sprague-Dawley rats given azathioprine in the diet for 3 to 4 weeks developed severe liver damage. Elevations of serum alkaline phosphatase and gamma-glutamyl transpeptidase activities were associated with increased hepatic glucose 6-phosphate dehydrogenase levels and decreased liver glucose 6-phosphatase activities, i.e., conditions which were commonly observed in various hepatotoxin-induced liver injuries. Light and electron microscopic observations revealed centrolobular necrosis with large scars and the proliferation of the mitochondria and rough endoplasmic reticulum. This model could be used to study the mechanisms of azathioprine-induced liver damage and its prevention.", "contents": "Biochemical and morphological study on hepatotoxicity of azathioprine in rat. Sprague-Dawley rats given azathioprine in the diet for 3 to 4 weeks developed severe liver damage. Elevations of serum alkaline phosphatase and gamma-glutamyl transpeptidase activities were associated with increased hepatic glucose 6-phosphate dehydrogenase levels and decreased liver glucose 6-phosphatase activities, i.e., conditions which were commonly observed in various hepatotoxin-induced liver injuries. Light and electron microscopic observations revealed centrolobular necrosis with large scars and the proliferation of the mitochondria and rough endoplasmic reticulum. This model could be used to study the mechanisms of azathioprine-induced liver damage and its prevention."}
{"id": "PMID:220847", "title": "A case of mesenchymoma in the oral cavity clinically resembling a large pleomorphic adenoma.", "content": "A report is made of a 52-year-old male whose main complaint was a painless tumor at the right side of the palate resulting in speech disturbance. He was diagnosed as a case of what Stout called benign mesenchymoma. Some discussion is also made of the tumor pathology in terms of genetic factors, predirective sites, age range, sex differences and therapy.", "contents": "A case of mesenchymoma in the oral cavity clinically resembling a large pleomorphic adenoma. A report is made of a 52-year-old male whose main complaint was a painless tumor at the right side of the palate resulting in speech disturbance. He was diagnosed as a case of what Stout called benign mesenchymoma. Some discussion is also made of the tumor pathology in terms of genetic factors, predirective sites, age range, sex differences and therapy."}
{"id": "PMID:220848", "title": "Detection and characterization of antibody to liver cell membrane in sera from patients with chronic active liver diseases.", "content": "Sera from 84 patients with chronic liver disease [CLD] (74 chronic active) and from 53 blood donors were tested immunochemically for anti-liver cell membrane antibody (LMAb). LMAb to rat liver tested by an indirect immunofluorescent technique was positive in 53.3% of CLD patients with positive HB surface antibody (HBsAb) and 40.0% of HBsAb positive blood donors. Pepsin digestion of the sera indicated that the binding between liver cell membrane and IgG was at the Fc site on the immunoglobulin. The sera with positive LMAb from HBsAb positive blood donors had elevated Clq-binding activity (Clq-BA). The LMAb to rat liver was a macro-molecular IgG (19-22S IgG) when assayed by Sephadex G-200 column chromatography and 5-40% sucrose density gradient ultracentrifugation. The results suggest that the LMAb in serum from a patient with chronic active liver disease may be an immune complex which consists of various antigens such as HB virus and its antibodies in serum.", "contents": "Detection and characterization of antibody to liver cell membrane in sera from patients with chronic active liver diseases. Sera from 84 patients with chronic liver disease [CLD] (74 chronic active) and from 53 blood donors were tested immunochemically for anti-liver cell membrane antibody (LMAb). LMAb to rat liver tested by an indirect immunofluorescent technique was positive in 53.3% of CLD patients with positive HB surface antibody (HBsAb) and 40.0% of HBsAb positive blood donors. Pepsin digestion of the sera indicated that the binding between liver cell membrane and IgG was at the Fc site on the immunoglobulin. The sera with positive LMAb from HBsAb positive blood donors had elevated Clq-binding activity (Clq-BA). The LMAb to rat liver was a macro-molecular IgG (19-22S IgG) when assayed by Sephadex G-200 column chromatography and 5-40% sucrose density gradient ultracentrifugation. The results suggest that the LMAb in serum from a patient with chronic active liver disease may be an immune complex which consists of various antigens such as HB virus and its antibodies in serum."}
{"id": "PMID:220849", "title": "Sarcoidosis presenting with diabetes insipidus followed by acute cranial nerve syndrome. A case report.", "content": "Diabetes insipidus in a previously healthy 16-year-old girl led to surgical exploration of a pituitary stalk intumescence detected by oxygen cisternography with the use of tomography. Biopsy of the pituitary stalk contained chronically inflamed brain tissue. Subsequent liver and bone biopsies showed characteristic granulomata, confirming the diagnosis of sarcoidosis. Subfrontal craniotomy was followed by a rapidly progressive basal meningoencephalitis with multiple cranial nerve involvement. The need to establish a causal diagnosis in diabetes insipidus is stressed. The rarity of the disorder and the presumed role of subfrontal craniotomy with regard to the flare-up of the sarcoidosis of the brain are discussed.", "contents": "Sarcoidosis presenting with diabetes insipidus followed by acute cranial nerve syndrome. A case report. Diabetes insipidus in a previously healthy 16-year-old girl led to surgical exploration of a pituitary stalk intumescence detected by oxygen cisternography with the use of tomography. Biopsy of the pituitary stalk contained chronically inflamed brain tissue. Subsequent liver and bone biopsies showed characteristic granulomata, confirming the diagnosis of sarcoidosis. Subfrontal craniotomy was followed by a rapidly progressive basal meningoencephalitis with multiple cranial nerve involvement. The need to establish a causal diagnosis in diabetes insipidus is stressed. The rarity of the disorder and the presumed role of subfrontal craniotomy with regard to the flare-up of the sarcoidosis of the brain are discussed."}
{"id": "PMID:220864", "title": "'Not Cushing's syndrome'.", "content": "Cushing's syndrome is characterized by protein wasting secondary to hypergluconeogenesis, which produces thin skin, poor muscle tone, osteoporosis and capillary fragility. These features distinguish patients with true Cushing's syndrome from those who have some of the clinical findings often associated with the syndrome, such as obesity, hypertension, striae and hirsutism. The dexamethasone suppression test helps identify patients with pseudo-Cushing's syndrome.", "contents": "'Not Cushing's syndrome'. Cushing's syndrome is characterized by protein wasting secondary to hypergluconeogenesis, which produces thin skin, poor muscle tone, osteoporosis and capillary fragility. These features distinguish patients with true Cushing's syndrome from those who have some of the clinical findings often associated with the syndrome, such as obesity, hypertension, striae and hirsutism. The dexamethasone suppression test helps identify patients with pseudo-Cushing's syndrome."}
{"id": "PMID:220865", "title": "Altered adrenergic activity in coronary arterial spasm: insight into mechanism based on study of coronary hemodynamics and the electrocardiogram.", "content": "To elucidate the pathophysiologic mechanism of coronary arterial spasm, the hypothesis was examined that underlying alterations in sympathetic activity may account for this syndrome in some patients. Observations were directed to alterations in coronary arterial hemodynamics and the electrocardiogram. Spasm of the left anterior descending coronary artery produced a mean increase in coronary vascular resistance of 107 percent (P less than 0.05) in four patients in whom coronary sinus blood flow was measured with the thermodilution technique. The alpha adrenergic blocking agent phentolamine, given intravenously, acutely reversed coronary spasm and its clinical manifestations in eight patients and reduced coronary resistance. In four patients, administration of the long-acting oral alpha blocking agent phenoxybenzamine (20 to 80 mg/day) caused disappearance of symptoms during a follow-up period of 3 to 12 months. Transient prolongation of the corrected Q-T interval preceded spontaneous or ergonovine maleate-provoked coronary spasm in 11 patients with variant angina pectoris, whereas no significant change in the Q-T interval followed ergonovine administration in 27 control patients with atypical chest pain who did not have coronary spasm. T wave inversions in the resting electrocardiogram were normalized by isoproterenol infusion in one patient and by long-term phenoxybenzamine treatment in four patients with variant angina pectoris. These Q-T and T wave changes are analogous to those described with unilateral or asymmetric stellate ganglion stimulation in animals. These observations suggest that alterations in the sympathetic nervous system that are consistent with asymmetric stellate ganglion activity and transient alpha adrenergic receptor stimulation can presage the development of coronary arterial spasm in some patients with variant angina pectoris.", "contents": "Altered adrenergic activity in coronary arterial spasm: insight into mechanism based on study of coronary hemodynamics and the electrocardiogram. To elucidate the pathophysiologic mechanism of coronary arterial spasm, the hypothesis was examined that underlying alterations in sympathetic activity may account for this syndrome in some patients. Observations were directed to alterations in coronary arterial hemodynamics and the electrocardiogram. Spasm of the left anterior descending coronary artery produced a mean increase in coronary vascular resistance of 107 percent (P less than 0.05) in four patients in whom coronary sinus blood flow was measured with the thermodilution technique. The alpha adrenergic blocking agent phentolamine, given intravenously, acutely reversed coronary spasm and its clinical manifestations in eight patients and reduced coronary resistance. In four patients, administration of the long-acting oral alpha blocking agent phenoxybenzamine (20 to 80 mg/day) caused disappearance of symptoms during a follow-up period of 3 to 12 months. Transient prolongation of the corrected Q-T interval preceded spontaneous or ergonovine maleate-provoked coronary spasm in 11 patients with variant angina pectoris, whereas no significant change in the Q-T interval followed ergonovine administration in 27 control patients with atypical chest pain who did not have coronary spasm. T wave inversions in the resting electrocardiogram were normalized by isoproterenol infusion in one patient and by long-term phenoxybenzamine treatment in four patients with variant angina pectoris. These Q-T and T wave changes are analogous to those described with unilateral or asymmetric stellate ganglion stimulation in animals. These observations suggest that alterations in the sympathetic nervous system that are consistent with asymmetric stellate ganglion activity and transient alpha adrenergic receptor stimulation can presage the development of coronary arterial spasm in some patients with variant angina pectoris."}
{"id": "PMID:220867", "title": "Serum lipid response to a high-caloric, high-fat diet in agricultural workers during 12 months.", "content": "The effect of a gluttony diet in healthy subjects was studied over an observation period of 12 months. Twenty-six agricultural workers, all of them Yemenite Jews, received a high-caloric, high-fat diet, and the changes in serum cholesterol (CH), high-density-lipoprotein-cholesterol, triglycerides, and body weight were assessed. Yemenite Jews as a group are characterized by low serum CH levels and by a low incidence of coronary artery disease. For a period of 7 months the subjects received a diet of 4553 cal/day, more than double their original \"Yemenite diet\". After this time they resumed their customary low-caloric diet for 3 months, and thereafter for another 2 months they continued with the high-caloric food regimen. The high-caloric, high-fat diet resulted in the expected increase of serum CH. A similar increase of high-density lipoprotein-CH was found. Serum triglyceride levels changed inversely to those of CH. It is suggested that the altered relation of calories derived from carbohydrates to those derived from fats brought about the decrease of triglycerides, and this irrespective of the increased intake of carbohydrates and fats. The rather small gain of body weight over the trial period--despite the doubled caloric intake--is similar to other studies that showed that the ability of normal individuals to gain weight through overeating varies considerably.", "contents": "Serum lipid response to a high-caloric, high-fat diet in agricultural workers during 12 months. The effect of a gluttony diet in healthy subjects was studied over an observation period of 12 months. Twenty-six agricultural workers, all of them Yemenite Jews, received a high-caloric, high-fat diet, and the changes in serum cholesterol (CH), high-density-lipoprotein-cholesterol, triglycerides, and body weight were assessed. Yemenite Jews as a group are characterized by low serum CH levels and by a low incidence of coronary artery disease. For a period of 7 months the subjects received a diet of 4553 cal/day, more than double their original \"Yemenite diet\". After this time they resumed their customary low-caloric diet for 3 months, and thereafter for another 2 months they continued with the high-caloric food regimen. The high-caloric, high-fat diet resulted in the expected increase of serum CH. A similar increase of high-density lipoprotein-CH was found. Serum triglyceride levels changed inversely to those of CH. It is suggested that the altered relation of calories derived from carbohydrates to those derived from fats brought about the decrease of triglycerides, and this irrespective of the increased intake of carbohydrates and fats. The rather small gain of body weight over the trial period--despite the doubled caloric intake--is similar to other studies that showed that the ability of normal individuals to gain weight through overeating varies considerably."}
{"id": "PMID:220869", "title": "Lymphosarcoma of the duodenum associated with carcinoma of the lung. Five-year survival.", "content": "The case presented describes a patient with lymphosarcoma of the duodenum associated with carcinoma of the lung. This emphasizes the basic problems which lymphosarcoma of the duodenum presents. They are vague symptoms until late in the course of the disease, the absence of early physical findings, the difficulty in interpretation of radiological studies and the frequent association with other primary malignancies elsewhere.", "contents": "Lymphosarcoma of the duodenum associated with carcinoma of the lung. Five-year survival. The case presented describes a patient with lymphosarcoma of the duodenum associated with carcinoma of the lung. This emphasizes the basic problems which lymphosarcoma of the duodenum presents. They are vague symptoms until late in the course of the disease, the absence of early physical findings, the difficulty in interpretation of radiological studies and the frequent association with other primary malignancies elsewhere."}
{"id": "PMID:220870", "title": "Metastatic carcinoma simulating linitis plastica of the colon. A case report.", "content": "Reported herein is the case of a 70-year old woman with metastatic breast carcinoma presenting as linitis plastica of the ascending colon. The breast tumor was diagnosed nine years previously. The clinical, roentgenographic and pathologic features of colonic linitis plastica and the preoperative diagnostic difficulties are discussed. There is no difference in the morphologic features of primary and secondary linitis plastica. The latter may result from anaplastic carcinoma of the stomach, gallbladder or breast.", "contents": "Metastatic carcinoma simulating linitis plastica of the colon. A case report. Reported herein is the case of a 70-year old woman with metastatic breast carcinoma presenting as linitis plastica of the ascending colon. The breast tumor was diagnosed nine years previously. The clinical, roentgenographic and pathologic features of colonic linitis plastica and the preoperative diagnostic difficulties are discussed. There is no difference in the morphologic features of primary and secondary linitis plastica. The latter may result from anaplastic carcinoma of the stomach, gallbladder or breast."}
{"id": "PMID:220871", "title": "Induced abortion and congenital malformations in offspring of subsequent pregnancies.", "content": "A case-control (n = 1427 and 3001, respectively) study in Connecticut found no relationship between delivery of an infant with congenital malformations and overall previous experience of induced abortion (odds ratio (o) = 0.9, 95% CL = 0.7, 1.1). Delivery of a congenitally malformed infant was also unrelated to: 1)abortion of penultimate pregnancy, 2) abortion of first pregnancy when index pregnancy is second, and 3) multiple previous abortions. Non-white women aged 25-29 who delivered a malformed child were significantly more likely to have aborted ( o = 2.6,95% CL = 1.2, 5.8, p less than 0.05). This may be due to more frequent histories of illegal and septic abortion, or to other characteristics of these women. Legal abortion performed under safe clinical conditions appears to impose no increased risk for subsequent delivery of a malformed infant.", "contents": "Induced abortion and congenital malformations in offspring of subsequent pregnancies. A case-control (n = 1427 and 3001, respectively) study in Connecticut found no relationship between delivery of an infant with congenital malformations and overall previous experience of induced abortion (odds ratio (o) = 0.9, 95% CL = 0.7, 1.1). Delivery of a congenitally malformed infant was also unrelated to: 1)abortion of penultimate pregnancy, 2) abortion of first pregnancy when index pregnancy is second, and 3) multiple previous abortions. Non-white women aged 25-29 who delivered a malformed child were significantly more likely to have aborted ( o = 2.6,95% CL = 1.2, 5.8, p less than 0.05). This may be due to more frequent histories of illegal and septic abortion, or to other characteristics of these women. Legal abortion performed under safe clinical conditions appears to impose no increased risk for subsequent delivery of a malformed infant."}
{"id": "PMID:220873", "title": "ProACTH: use for early detection of lung cancer.", "content": "ProACTH was identified by radioimmunoassay and column chromatography in extracts of 38 lung carcinomas. One hundred patients were evaluated because of abnormalities on chest roentgenograms; 53 (72 per cent) of 74 with lung cancers had increased plasma ACTH immunoreactivity; all 26 with benign abnormalities had normal ACTH. Of 101 patients with obstructive lung disease, five of 20 with elevated plasma ACTH levels and two of 81 with normal plasma ACTH levels had lung cancer within two years. In three of 31 patients with granulomatous lung disease plasma ACTH levels were elevated during acute exacerbation of the disease, but they returned to normal after recovery. We conclude that plasma ACTH immunoreactivity is frequently increased early in the course of lung carcinoma.", "contents": "ProACTH: use for early detection of lung cancer. ProACTH was identified by radioimmunoassay and column chromatography in extracts of 38 lung carcinomas. One hundred patients were evaluated because of abnormalities on chest roentgenograms; 53 (72 per cent) of 74 with lung cancers had increased plasma ACTH immunoreactivity; all 26 with benign abnormalities had normal ACTH. Of 101 patients with obstructive lung disease, five of 20 with elevated plasma ACTH levels and two of 81 with normal plasma ACTH levels had lung cancer within two years. In three of 31 patients with granulomatous lung disease plasma ACTH levels were elevated during acute exacerbation of the disease, but they returned to normal after recovery. We conclude that plasma ACTH immunoreactivity is frequently increased early in the course of lung carcinoma."}
{"id": "PMID:220874", "title": "Fulminating hypercalcemia and markedly increased nephrogenous cyclic AMP in a patient with transitional cell carcinoma of the bladder.", "content": "Refractory hypercalcemia developed suddenly in a patient who had undergone a radical cystectomy for an anaplastic transitional cell carcinoma of the bladder. A normal serum parathyroid hormone (PTH) value was obtained by immunoassay while the patient had hypercalcemia and unimpaired renal function. This normal PTH value in the presence of hypercalcemia was consistent with his hypercalcemia being secondary to excessive amounts of circulating PTH. The finding of increased nephrogenous cyclic AMP, however, provided the definitive diagnosis of hyyperparathyroidism. Since autopsy revealed that there was no residual tumor in the bladder area, only evidence of metastatic disease, and since the parathyroid glands were not hyperplastic or adenomatous, we attributed this patient's hypercalcemia to hyperparathyroidism due to the ectopic production of PTH by a metastasis from the transitional cell carcinoma of the bladder.", "contents": "Fulminating hypercalcemia and markedly increased nephrogenous cyclic AMP in a patient with transitional cell carcinoma of the bladder. Refractory hypercalcemia developed suddenly in a patient who had undergone a radical cystectomy for an anaplastic transitional cell carcinoma of the bladder. A normal serum parathyroid hormone (PTH) value was obtained by immunoassay while the patient had hypercalcemia and unimpaired renal function. This normal PTH value in the presence of hypercalcemia was consistent with his hypercalcemia being secondary to excessive amounts of circulating PTH. The finding of increased nephrogenous cyclic AMP, however, provided the definitive diagnosis of hyyperparathyroidism. Since autopsy revealed that there was no residual tumor in the bladder area, only evidence of metastatic disease, and since the parathyroid glands were not hyperplastic or adenomatous, we attributed this patient's hypercalcemia to hyperparathyroidism due to the ectopic production of PTH by a metastasis from the transitional cell carcinoma of the bladder."}
{"id": "PMID:220875", "title": "Effects of long-term estrogen replacement therapy. II. Neoplasia.", "content": "Two groups of hypoestrogenic women are analyzed by retrospective comparison. Patients were observed by a single group of physicians for at least five years -- 301 patients treated with replacement estrogen and 309 untreated patients. Of each group, 207 women had uteri in situ. Incidence figures for neoplasia (gynecologic, breast, and all sites) were compared between the two groups and with the Third National Cancer Survey, yielding a risk ratio for the development of adenocarcinoma of the endometrium among estrogen-treated women of 3.8 and 9.3, respectively. There was no increase among any other malignancies. The addition of synthetic progestin to estrogen therapy provided significant protection against the likelihood of developing endometrial cancer and did not reduce previously reported metabolic benefits of estrogen treatment. Data pertaining to estrogen use and details of the patients with endometrial carcinoma are presented.", "contents": "Effects of long-term estrogen replacement therapy. II. Neoplasia. Two groups of hypoestrogenic women are analyzed by retrospective comparison. Patients were observed by a single group of physicians for at least five years -- 301 patients treated with replacement estrogen and 309 untreated patients. Of each group, 207 women had uteri in situ. Incidence figures for neoplasia (gynecologic, breast, and all sites) were compared between the two groups and with the Third National Cancer Survey, yielding a risk ratio for the development of adenocarcinoma of the endometrium among estrogen-treated women of 3.8 and 9.3, respectively. There was no increase among any other malignancies. The addition of synthetic progestin to estrogen therapy provided significant protection against the likelihood of developing endometrial cancer and did not reduce previously reported metabolic benefits of estrogen treatment. Data pertaining to estrogen use and details of the patients with endometrial carcinoma are presented."}
{"id": "PMID:220877", "title": "Endocrine studies of normal and polycystic ovarian tissues in vitro.", "content": "The purpose of this study was to compare the steroidogenic potential of the granulosa, theca, and medullary tissues from polycystic and normal ovaries. These ovarian endocrine compartments were isolated from appropriate ovaries and were cultured in vitro for three days in the absence (control) and presence of follicle-stimulating hormone (FSH)/luteinizing hormone (LH) (1 lU/ml), N6,O2-dibutyryladenosine-3':5''-cyclic monophosphoric acid (Bu2cAMP) (10(-2)M), and adrenocorticotropic hormone (ACTH) (1.3 U/ml). After the incubation, steroids in the media were measured by radioimmunoassay. Granulosa cells (10(5) cells per dish) from 4 to 7 mm follicles of normal and polycystic ovaries secreted progesterone spontaneously during the culture period and the production of progesterone was markedly stimulated (between tenfold and thirtyfold) by gonadotropins and Bu2cAMP but not by ACTH. Little, if any, androgen (androstenedione, dehydroepiandrosterone, and testosterone) or estrogen (estrone and estradiol) accumulated in the media of any granulosa cell culture. The control cultures of theca tissue from normal and polycystic ovaries secreted large amounts of androstenedione and progesterone and the production of these steroids by normal and polycystic ovary theca was stimulated in most cases by LH/FSH and Bu2cAMP but not by ACTH. Both normal and polycystic ovary theca secreted some testosterone and dehydroepiandrosterone but little, if any, estrone or estradiol accumulated in any theca culture. The medullary tissue of normal and polycystic ovaries produced only trace amounts of steroids in vitro except for the results from one polycystic ovary with hyperthecosis in which case significant quantities of C19 and C18 steroids were secreted. These experiments have demonstrated that isolated granulosa and theca cells from midantral follicles of normal and polycystic ovaries have a similar capacity to secrete C21 and C19 steroids in the absence and presence of trophic agents. Therefore, it seems probable that chronic anovulation in patients with polycystic ovaries is not caused by an obvious deficiency in the de novo steroidogenic potential of the multiple midantral follicles of the polycystic ovaries or by the absence of gonadotropin receptors on the polycystic ovary follicular cells.", "contents": "Endocrine studies of normal and polycystic ovarian tissues in vitro. The purpose of this study was to compare the steroidogenic potential of the granulosa, theca, and medullary tissues from polycystic and normal ovaries. These ovarian endocrine compartments were isolated from appropriate ovaries and were cultured in vitro for three days in the absence (control) and presence of follicle-stimulating hormone (FSH)/luteinizing hormone (LH) (1 lU/ml), N6,O2-dibutyryladenosine-3':5''-cyclic monophosphoric acid (Bu2cAMP) (10(-2)M), and adrenocorticotropic hormone (ACTH) (1.3 U/ml). After the incubation, steroids in the media were measured by radioimmunoassay. Granulosa cells (10(5) cells per dish) from 4 to 7 mm follicles of normal and polycystic ovaries secreted progesterone spontaneously during the culture period and the production of progesterone was markedly stimulated (between tenfold and thirtyfold) by gonadotropins and Bu2cAMP but not by ACTH. Little, if any, androgen (androstenedione, dehydroepiandrosterone, and testosterone) or estrogen (estrone and estradiol) accumulated in the media of any granulosa cell culture. The control cultures of theca tissue from normal and polycystic ovaries secreted large amounts of androstenedione and progesterone and the production of these steroids by normal and polycystic ovary theca was stimulated in most cases by LH/FSH and Bu2cAMP but not by ACTH. Both normal and polycystic ovary theca secreted some testosterone and dehydroepiandrosterone but little, if any, estrone or estradiol accumulated in any theca culture. The medullary tissue of normal and polycystic ovaries produced only trace amounts of steroids in vitro except for the results from one polycystic ovary with hyperthecosis in which case significant quantities of C19 and C18 steroids were secreted. These experiments have demonstrated that isolated granulosa and theca cells from midantral follicles of normal and polycystic ovaries have a similar capacity to secrete C21 and C19 steroids in the absence and presence of trophic agents. Therefore, it seems probable that chronic anovulation in patients with polycystic ovaries is not caused by an obvious deficiency in the de novo steroidogenic potential of the multiple midantral follicles of the polycystic ovaries or by the absence of gonadotropin receptors on the polycystic ovary follicular cells."}
{"id": "PMID:220878", "title": "Peripheral rheumatoid ulceration and evidence for conjunctival collagenase production.", "content": "Two patients with rheumatoid arthritis and peripheral corneal ulcerations were successfully treated by conjunctival resection. The tissues removed were assayed by a variation of the radial diffusion method for tissue collagenases. We used an agarose matrix containing lathyritic rat skin collagen. Wells 3 mm deep were punched in the agarose-collagen and surgical specimens were placed in the wells. Spaces remaining in the wells were filled with balanced salt solution. The assay dishes were incubated for four days at 32 degrees C near 100% humidity. Under these conditions release of collagenase was detected by the clearing of diffuse zones in the gel surrounding the well. Conjunctiva proximal to the ulcer produced definite zones of lysis, whereas control specimens taken remote to the ulceration produced no lysis. This direct evidence for collagenase involvement offers an exploration for the beneficial effects of conjunctival resection.", "contents": "Peripheral rheumatoid ulceration and evidence for conjunctival collagenase production. Two patients with rheumatoid arthritis and peripheral corneal ulcerations were successfully treated by conjunctival resection. The tissues removed were assayed by a variation of the radial diffusion method for tissue collagenases. We used an agarose matrix containing lathyritic rat skin collagen. Wells 3 mm deep were punched in the agarose-collagen and surgical specimens were placed in the wells. Spaces remaining in the wells were filled with balanced salt solution. The assay dishes were incubated for four days at 32 degrees C near 100% humidity. Under these conditions release of collagenase was detected by the clearing of diffuse zones in the gel surrounding the well. Conjunctiva proximal to the ulcer produced definite zones of lysis, whereas control specimens taken remote to the ulceration produced no lysis. This direct evidence for collagenase involvement offers an exploration for the beneficial effects of conjunctival resection."}
{"id": "PMID:220879", "title": "Application of the likelihood ratio test to age estimation using the infant and child temporal bone.", "content": "Several developmental changes in the skull of infants and children are well documented and have been used in the estimation of age at death of infants and children. This paper will present a feature of the infant and child temporal bone, the development of the tympanic plate (floor) of the external auditory meatus, which has recently proven useful in age estimation. Through the use of the Likelihood Ratio Test (Sprott, '73), a six-stage developmental sequence for the tympanic plate has been evaluated. Analysis of tthe tympanic plate developmental sequence has produced the following age categories: fetal, newborn, six months, one to two and one-half years. A general discussion of the basis and potential applications of the Likelihood Ratio Test for analysis of stages and other ordinal data is offered.", "contents": "Application of the likelihood ratio test to age estimation using the infant and child temporal bone. Several developmental changes in the skull of infants and children are well documented and have been used in the estimation of age at death of infants and children. This paper will present a feature of the infant and child temporal bone, the development of the tympanic plate (floor) of the external auditory meatus, which has recently proven useful in age estimation. Through the use of the Likelihood Ratio Test (Sprott, '73), a six-stage developmental sequence for the tympanic plate has been evaluated. Analysis of tthe tympanic plate developmental sequence has produced the following age categories: fetal, newborn, six months, one to two and one-half years. A general discussion of the basis and potential applications of the Likelihood Ratio Test for analysis of stages and other ordinal data is offered."}
{"id": "PMID:220880", "title": "Correlated release of acetylcholine and protein from the neuromuscular junction.", "content": "Transmitter release at adrenergic synapses is accompanied by release of chromogranin proteins, which are contained in synaptic vesicles. To determine if a similar phenomenon occurs at the neuromuscular junction, correlated release of acetylcholine (ACh) and protein was investigated using in vitro neuromuscular preparations (phrenic nerve-diaphragm muscle of the rat and mouse, sciatic nerve-sartorius muscle of Rana pipiens and R. catesbeiana). Nerve stimulation of curare-paralyzed preparations increased the rate of efflux of Lowry-reactive material relative to control values. Stimulus-specific responses outlasted the period of neural stimulation. Stimulus-induced release of Lowry-reactive material was correlated with ACh release since it was Ca2+ dependent and Mg2+ antagonized. Conditions that potentiate spontaneous ACh release also significantly increased the rate of efflux of Lowry-reactive material. Most of the Lowry-reactive material released with ACh is not a secretory product of synaptic vesicles because the amount released exceeds the contents of synaptic vesicles that undergo exocytosis. It is concluded that ACh release from the neuromuscular junction is accompanied by release of proteinaceous material that is not entirely derived from synaptic vesicles.", "contents": "Correlated release of acetylcholine and protein from the neuromuscular junction. Transmitter release at adrenergic synapses is accompanied by release of chromogranin proteins, which are contained in synaptic vesicles. To determine if a similar phenomenon occurs at the neuromuscular junction, correlated release of acetylcholine (ACh) and protein was investigated using in vitro neuromuscular preparations (phrenic nerve-diaphragm muscle of the rat and mouse, sciatic nerve-sartorius muscle of Rana pipiens and R. catesbeiana). Nerve stimulation of curare-paralyzed preparations increased the rate of efflux of Lowry-reactive material relative to control values. Stimulus-specific responses outlasted the period of neural stimulation. Stimulus-induced release of Lowry-reactive material was correlated with ACh release since it was Ca2+ dependent and Mg2+ antagonized. Conditions that potentiate spontaneous ACh release also significantly increased the rate of efflux of Lowry-reactive material. Most of the Lowry-reactive material released with ACh is not a secretory product of synaptic vesicles because the amount released exceeds the contents of synaptic vesicles that undergo exocytosis. It is concluded that ACh release from the neuromuscular junction is accompanied by release of proteinaceous material that is not entirely derived from synaptic vesicles."}
{"id": "PMID:220881", "title": "Is the function of the renal papilla coupled exclusively to an anaerobic pattern of metabolism?", "content": "It is widely accepted that in vivo the function of the papilla of the mammalian kidney is supported primarily by anaerobic metabolism. As a result, the major source of energy for support of function in the papilla is considered to be derived from glycolysis. This orientation originates from two concepts: 1) that in vivo the gaseous environment of the papilla has such a low PO2 that O2 availability limits O2 consumption, and 2) that papillary tissue has a high rate of glycolysis when compared with either cortical tissue or extrarenal tissues. It has also been tacitly assumed that papillary tissue has a \"low\" O2 uptake. Review of the measurements of PO2 of papillary tissue and of urine PO2 indicates that the PO2 of papillary tissue should not limit its aerobic mitochondrial oxidative metabolism. While the rate of aerobic glycolysis in papillary tissue is high, simultaneously papillary tissue has a rate of O2 uptake similar to that of liver and higher than that of muscle. The major (two-thirds) source of energy for papillary tissue in vitro is from O2 uptake. That papillary tissue is not exclusively dependent on glucose for its energy requirements is indicated by the greater stimulation of papillary tissue QO2 by succinate than by glucose. Thus, papillary tissue has both a high aerobic mitochondrial oxidative metabolism and a high aerobic glycolytic metabolism. It is suggested that the mechanism for the high rate of aerobic glycolysis in the presence of an adequate O2 supply is due to the relatively small mass of mitochondria in papillary tissue in relation to the amount of work done by the tissue. As a result of the limited rate of ATP production by the mitochondrial electron transport chain, the phosphorylation state ([ATP]/[ADP][Pi]) is reduced and the cytoplasmic redox state ([NAD+]/[NADH]) of the papillary collecting duct cells also becomes more reduced; changes in both ratios enhance the rate of glycolysis. This limited metabolic capacity of the collecting duct cells may permit an excess volume of solute and water to be excreted during volume expansion diuresis. The metabolic characteristics of the papilla, when compared to cortex, also provide a basis for the observed differences in substrate selectivity of cortex and medulla with respect to utilization of glucose and lactate. The experimental approaches that may provide information bearing on the suggested mechanisms for regulation of papillary metabolism in relation to tubular work functions are indicated.", "contents": "Is the function of the renal papilla coupled exclusively to an anaerobic pattern of metabolism? It is widely accepted that in vivo the function of the papilla of the mammalian kidney is supported primarily by anaerobic metabolism. As a result, the major source of energy for support of function in the papilla is considered to be derived from glycolysis. This orientation originates from two concepts: 1) that in vivo the gaseous environment of the papilla has such a low PO2 that O2 availability limits O2 consumption, and 2) that papillary tissue has a high rate of glycolysis when compared with either cortical tissue or extrarenal tissues. It has also been tacitly assumed that papillary tissue has a \"low\" O2 uptake. Review of the measurements of PO2 of papillary tissue and of urine PO2 indicates that the PO2 of papillary tissue should not limit its aerobic mitochondrial oxidative metabolism. While the rate of aerobic glycolysis in papillary tissue is high, simultaneously papillary tissue has a rate of O2 uptake similar to that of liver and higher than that of muscle. The major (two-thirds) source of energy for papillary tissue in vitro is from O2 uptake. That papillary tissue is not exclusively dependent on glucose for its energy requirements is indicated by the greater stimulation of papillary tissue QO2 by succinate than by glucose. Thus, papillary tissue has both a high aerobic mitochondrial oxidative metabolism and a high aerobic glycolytic metabolism. It is suggested that the mechanism for the high rate of aerobic glycolysis in the presence of an adequate O2 supply is due to the relatively small mass of mitochondria in papillary tissue in relation to the amount of work done by the tissue. As a result of the limited rate of ATP production by the mitochondrial electron transport chain, the phosphorylation state ([ATP]/[ADP][Pi]) is reduced and the cytoplasmic redox state ([NAD+]/[NADH]) of the papillary collecting duct cells also becomes more reduced; changes in both ratios enhance the rate of glycolysis. This limited metabolic capacity of the collecting duct cells may permit an excess volume of solute and water to be excreted during volume expansion diuresis. The metabolic characteristics of the papilla, when compared to cortex, also provide a basis for the observed differences in substrate selectivity of cortex and medulla with respect to utilization of glucose and lactate. The experimental approaches that may provide information bearing on the suggested mechanisms for regulation of papillary metabolism in relation to tubular work functions are indicated."}
{"id": "PMID:220883", "title": "Evidence for existence of cortical androgen-stimulating hormone.", "content": "An animal model using dexamethosone-suppressed, castrated dogs was developed to test the hypothesis that a pituitary hormone other than ACTH modulates adrenal androgen (AA) secretion. Plasma samples were obtained every 15 min during infusions of saline, synthetic alpha 1-24 corticotropin, porcine 1-39 corticotropin (ACTH), or bovine pituitary gland extract (PE) in a wide range of doses. Androstenedione (A), dehydroepiandrosterone (DHA), and cortisol (F) were quantified by radioimmunoassay. When the ratio of AA levels was related to those of F, in order to correct for ACTH content in the PE, the slopes of the dose-response curves for corticotropin and PE were different at the 0.01 level. For A the dose-response slope for the PE was 0.18 +/- 0.5 SE, whereas that of ACTH was 0.02 +/- 0.01. For the DHA response the slopes were 0.17 +/- 0.04 for the PE and 0.04 +/- 0.03 for ACTH. Related studies showed no increase in AA levels in response to luteinizing hormone-releasing hormone, bovine growth hormone (GH), bovine prolactin, ovine thyroid-stimulating hormone (TSH), or synthetic aqueous arginine vasopressin (AVP). We conclude that a pituitary factor other than ACTH, prolactin, GH, luteinizing hormone, follicle-stimulating hormone, TSH, or AVP may be responsible for the observed increase in AA concentrations.", "contents": "Evidence for existence of cortical androgen-stimulating hormone. An animal model using dexamethosone-suppressed, castrated dogs was developed to test the hypothesis that a pituitary hormone other than ACTH modulates adrenal androgen (AA) secretion. Plasma samples were obtained every 15 min during infusions of saline, synthetic alpha 1-24 corticotropin, porcine 1-39 corticotropin (ACTH), or bovine pituitary gland extract (PE) in a wide range of doses. Androstenedione (A), dehydroepiandrosterone (DHA), and cortisol (F) were quantified by radioimmunoassay. When the ratio of AA levels was related to those of F, in order to correct for ACTH content in the PE, the slopes of the dose-response curves for corticotropin and PE were different at the 0.01 level. For A the dose-response slope for the PE was 0.18 +/- 0.5 SE, whereas that of ACTH was 0.02 +/- 0.01. For the DHA response the slopes were 0.17 +/- 0.04 for the PE and 0.04 +/- 0.03 for ACTH. Related studies showed no increase in AA levels in response to luteinizing hormone-releasing hormone, bovine growth hormone (GH), bovine prolactin, ovine thyroid-stimulating hormone (TSH), or synthetic aqueous arginine vasopressin (AVP). We conclude that a pituitary factor other than ACTH, prolactin, GH, luteinizing hormone, follicle-stimulating hormone, TSH, or AVP may be responsible for the observed increase in AA concentrations."}
{"id": "PMID:220884", "title": "Insulin inhibition of hormone-stimulated protein kinase systems of rat renal cortex.", "content": "Parathyroid hormone (PTH) and glucagon increase the urinary fractional excretion of phosphate, but insulin administration is associated with a decreased fractional excretion of phosphate. It was the purpose of this study to determine whether insulin will antagonize the effects of PTH and glucagon on cAMP levels and protein kinase activation of rat renal cortex. In situ incubation studies were performed on rat renal cortical slices exposed to insulin, PTH, and glucagon. Insulin alone did not affect the tissue cAMP and cGMP levels or the state of protein kinase activation. Preincubation of slices with insulin, however, did significantly inhibit increases in protein kinase activation induced by both PTH and glucagon. Insulin also significantly inhibited PTH-stimulated increases in tissue cAMP levels, but did not blunt the elevations of cAMP levels induced by glucagon. Insulin (10(-9) M) had no effect on either the in vitro activity of adenylate cyclase, basal or PTH-stimulated, or on the activities of low Km cytosolic or membrane-bound cAMP phosphodiesterase. The data show that insulin antagonizes activation of protein kinase by both PTH and glucagon in renal cortex. Separate mechanisms are probably involved for PTH and glucagon interaction. The antiphosphaturic effect of insulin in vivo may result in part from this antagonism at the cellular level.", "contents": "Insulin inhibition of hormone-stimulated protein kinase systems of rat renal cortex. Parathyroid hormone (PTH) and glucagon increase the urinary fractional excretion of phosphate, but insulin administration is associated with a decreased fractional excretion of phosphate. It was the purpose of this study to determine whether insulin will antagonize the effects of PTH and glucagon on cAMP levels and protein kinase activation of rat renal cortex. In situ incubation studies were performed on rat renal cortical slices exposed to insulin, PTH, and glucagon. Insulin alone did not affect the tissue cAMP and cGMP levels or the state of protein kinase activation. Preincubation of slices with insulin, however, did significantly inhibit increases in protein kinase activation induced by both PTH and glucagon. Insulin also significantly inhibited PTH-stimulated increases in tissue cAMP levels, but did not blunt the elevations of cAMP levels induced by glucagon. Insulin (10(-9) M) had no effect on either the in vitro activity of adenylate cyclase, basal or PTH-stimulated, or on the activities of low Km cytosolic or membrane-bound cAMP phosphodiesterase. The data show that insulin antagonizes activation of protein kinase by both PTH and glucagon in renal cortex. Separate mechanisms are probably involved for PTH and glucagon interaction. The antiphosphaturic effect of insulin in vivo may result in part from this antagonism at the cellular level."}
{"id": "PMID:220885", "title": "Inhibition of H+ secretion in frog gastric mucosa by somatostatin.", "content": "Somatostatin added to the serosal bathing solution of the isolated gastric mucosa of Rana pipiens significantly inhibited pentagastrin- and histamine-stimulated H+ secretion. The decrease in H+ secretion rate was accompanied by an increase in the transmucosal potential difference and resistance. Somatostatin (10(-5) M) had no effect on the N6,O2-dibutyryl adenosine 3'-5'-cyclic monophosphate (DBcAMP)-stimulated H+ secretion rate. The mucosa exposed to somatostatin secreted H+ on stimulation by DBcAMP or histamine, but did not respond to 2.8 X 10(-7) M pentagastrin. However, pentagastrin added to the serosal solution stimulated H+ secretion after the somatostatin was washed away. Calcium inophore (3 X 10(-5) M) alone or 10(-2) M Ca2+ plus calcium ionophore temporarily increased the H+ secretion rate inhibited by somatostatin. The data suggest that somatostatin has a direct effect on the oxyntic cells in the gastric mucosa.", "contents": "Inhibition of H+ secretion in frog gastric mucosa by somatostatin. Somatostatin added to the serosal bathing solution of the isolated gastric mucosa of Rana pipiens significantly inhibited pentagastrin- and histamine-stimulated H+ secretion. The decrease in H+ secretion rate was accompanied by an increase in the transmucosal potential difference and resistance. Somatostatin (10(-5) M) had no effect on the N6,O2-dibutyryl adenosine 3'-5'-cyclic monophosphate (DBcAMP)-stimulated H+ secretion rate. The mucosa exposed to somatostatin secreted H+ on stimulation by DBcAMP or histamine, but did not respond to 2.8 X 10(-7) M pentagastrin. However, pentagastrin added to the serosal solution stimulated H+ secretion after the somatostatin was washed away. Calcium inophore (3 X 10(-5) M) alone or 10(-2) M Ca2+ plus calcium ionophore temporarily increased the H+ secretion rate inhibited by somatostatin. The data suggest that somatostatin has a direct effect on the oxyntic cells in the gastric mucosa."}
{"id": "PMID:220886", "title": "Uric acid transport in brush border membrane vesicles isolated from rabbit kidney.", "content": "The transport of uric acid was studied in brush border membrane vesicles isolated from rabbit kidney. The uptake of uric acid by the vesicles was osmotically sensitive and occurred in the absence of significant uric acid degradation. Under the conditions used to evaluate transport, urate binding to the membranes represented only 10--15% of the total uptake. The initial rate of uptake was linear over the concentration range 0.04--8 mM urate. Uptake of urage was Na+ gradient independent. It was dependent on external pH and temperature with Q10 near 3. The urate uptake was inhibited reversibly by p-chloromercuribenzoate. Probenecid, ouabain, cyclic adenosine 3',5'--monophosphate, and its dibutyryl derivative had no appreciable effects. Pyrazinoic acid and pyrazinamide stimulated urate uptake. Experiments performed with osmotically shocked vesicles demonstrated that this stimulatory effect resulted from increased binding of urate to the membranes. These results indicate that in several ways urate transport in vesicles resembles that observed with more physiologically intact preparations.", "contents": "Uric acid transport in brush border membrane vesicles isolated from rabbit kidney. The transport of uric acid was studied in brush border membrane vesicles isolated from rabbit kidney. The uptake of uric acid by the vesicles was osmotically sensitive and occurred in the absence of significant uric acid degradation. Under the conditions used to evaluate transport, urate binding to the membranes represented only 10--15% of the total uptake. The initial rate of uptake was linear over the concentration range 0.04--8 mM urate. Uptake of urage was Na+ gradient independent. It was dependent on external pH and temperature with Q10 near 3. The urate uptake was inhibited reversibly by p-chloromercuribenzoate. Probenecid, ouabain, cyclic adenosine 3',5'--monophosphate, and its dibutyryl derivative had no appreciable effects. Pyrazinoic acid and pyrazinamide stimulated urate uptake. Experiments performed with osmotically shocked vesicles demonstrated that this stimulatory effect resulted from increased binding of urate to the membranes. These results indicate that in several ways urate transport in vesicles resembles that observed with more physiologically intact preparations."}
{"id": "PMID:220888", "title": "Effects of the oral converting enzyme inhibitor SQ 14225 in experimental high output failure.", "content": "The relation of the renin-angiotensin-aldosterone system to sodium retention was studied in dogs with an aortic-caval fistula and high output failure by administering orally the new converting enzyme inhibitor SQ 14225. The acute response to an initial oral dose of SQ 14225 (10 mg/kg) consisted in a fall in arterial pressure (BP) from 97 to 67 mmHg, plasma aldosterone concentration (PAC) from 21.7 to 11.3 ng/100 ml, creatinine clearance (CCr) from 89 to 44 ml/min, and filtration fraction (FF) from 39 to 18%, whereas plasma renin activity (PRA) increases from 12.7 to 36.1 ng angiotensin I.ml-1.h-1 and renal sodium excretion was unchanged. It is suggested that the marked fall in BP and CCr offset the drop in PAC and FF which favored a natriuresis. The daily responses to SQ 14225 for 3 days also showed a fall in BP and PAC but sodium excretion increased. In the animal with the best response, a striking natriuresis occurred. These findings demonstrate an important role for the renin-angiotensin-aldosterone system in experimental high output failure.", "contents": "Effects of the oral converting enzyme inhibitor SQ 14225 in experimental high output failure. The relation of the renin-angiotensin-aldosterone system to sodium retention was studied in dogs with an aortic-caval fistula and high output failure by administering orally the new converting enzyme inhibitor SQ 14225. The acute response to an initial oral dose of SQ 14225 (10 mg/kg) consisted in a fall in arterial pressure (BP) from 97 to 67 mmHg, plasma aldosterone concentration (PAC) from 21.7 to 11.3 ng/100 ml, creatinine clearance (CCr) from 89 to 44 ml/min, and filtration fraction (FF) from 39 to 18%, whereas plasma renin activity (PRA) increases from 12.7 to 36.1 ng angiotensin I.ml-1.h-1 and renal sodium excretion was unchanged. It is suggested that the marked fall in BP and CCr offset the drop in PAC and FF which favored a natriuresis. The daily responses to SQ 14225 for 3 days also showed a fall in BP and PAC but sodium excretion increased. In the animal with the best response, a striking natriuresis occurred. These findings demonstrate an important role for the renin-angiotensin-aldosterone system in experimental high output failure."}
{"id": "PMID:220889", "title": "beta-Endorphin and naloxone in psychiatric patients: clinical and biological effects.", "content": "The authors conducted single- and double-blind studies of the responses of 7 chronic male schizophrenic patients to 10 mg of naloxone. BPRS ratings were made before and 6 hours after the injection; ACTH blood levels were determined before and 1 1/2 and 6 hours after injection. Statistically significant improvement of psychotic behavior occurred after 6 hours. The greatest improvement occurred in the patient who showed the most pronounced diurnal variation of ACTH levels, and there was no improvement in the patient who had no diurnal changes. Prolactin plasma levels following endorphin injections were apparently dose-dependent and peaked at approximately 30 minutes. The mean half-life of elimination of exogenous beta-endorphin was between 12 and 35 minutes. The authors theorize that positive and negative behavioral responses to naloxone depend--as possibly do many placebo responses in general--on the relative stress produced by experimental or therapeutic interventions.", "contents": "beta-Endorphin and naloxone in psychiatric patients: clinical and biological effects. The authors conducted single- and double-blind studies of the responses of 7 chronic male schizophrenic patients to 10 mg of naloxone. BPRS ratings were made before and 6 hours after the injection; ACTH blood levels were determined before and 1 1/2 and 6 hours after injection. Statistically significant improvement of psychotic behavior occurred after 6 hours. The greatest improvement occurred in the patient who showed the most pronounced diurnal variation of ACTH levels, and there was no improvement in the patient who had no diurnal changes. Prolactin plasma levels following endorphin injections were apparently dose-dependent and peaked at approximately 30 minutes. The mean half-life of elimination of exogenous beta-endorphin was between 12 and 35 minutes. The authors theorize that positive and negative behavioral responses to naloxone depend--as possibly do many placebo responses in general--on the relative stress produced by experimental or therapeutic interventions."}
{"id": "PMID:220890", "title": "Research and development of naltrexone: a new narcotic antagonist.", "content": "The author reviews the history of federally supported research in the field of narcotic antagonist therapy, focusing on social, political, and governmental issues. He describes the criteria for establishing an optimum narcotic antagonist, the legal guidelines for drug development, and the currently available narcotic antagonists. Research supported by the National Institute on Drug Abuse has indicated that naltrexone is the most promising drug in this category. The author discusses the safety and clinic use of naltrexone, the status of the NIDA naltrexone program, and plans for future development of the drug.", "contents": "Research and development of naltrexone: a new narcotic antagonist. The author reviews the history of federally supported research in the field of narcotic antagonist therapy, focusing on social, political, and governmental issues. He describes the criteria for establishing an optimum narcotic antagonist, the legal guidelines for drug development, and the currently available narcotic antagonists. Research supported by the National Institute on Drug Abuse has indicated that naltrexone is the most promising drug in this category. The author discusses the safety and clinic use of naltrexone, the status of the NIDA naltrexone program, and plans for future development of the drug."}
{"id": "PMID:220893", "title": "Alterations in hepatocytes of mice fed a gallstone-inducing diet: occurrence of nuclear and cytoplasmic lipids.", "content": "Mice fed a high cholesterol-cholic acid (lithogenic) diet for one year develop fatty livers in addition to gallstones. Light and electron micrographs demonstrate large amounts of lipids in liver parenchymal cells, often to the exclusion of most other cytoplasmic organelles. In addition, some hepatocytes exhibit nuclear lipid pseudo- and true inclusions. Other prominent features of hepatocytes after lithogenic diet include segregation of nucleolar granular and fibrillar material. Accumulation of considerable collagen in extracellular spaces is also noted. Observations suggest changes induced by the cholesterol diet are comparable to cytologic alterations seen in spontaneous and drug induced hepatic tumors, as well as to more general \"fatty metamorphosis\" of the liver.", "contents": "Alterations in hepatocytes of mice fed a gallstone-inducing diet: occurrence of nuclear and cytoplasmic lipids. Mice fed a high cholesterol-cholic acid (lithogenic) diet for one year develop fatty livers in addition to gallstones. Light and electron micrographs demonstrate large amounts of lipids in liver parenchymal cells, often to the exclusion of most other cytoplasmic organelles. In addition, some hepatocytes exhibit nuclear lipid pseudo- and true inclusions. Other prominent features of hepatocytes after lithogenic diet include segregation of nucleolar granular and fibrillar material. Accumulation of considerable collagen in extracellular spaces is also noted. Observations suggest changes induced by the cholesterol diet are comparable to cytologic alterations seen in spontaneous and drug induced hepatic tumors, as well as to more general \"fatty metamorphosis\" of the liver."}
{"id": "PMID:220894", "title": "Polymorphism of 14C vitamin D3 binding protein in cattle and water buffalo serum.", "content": "Cattle and water buffalo sera labelled with vitamin D3[14C] (300 and 480 individual samples respectively) were subjected to starch gel electrophoresis followed by autoradiography in an attempt to identify a possible polymorphism of the proteins capable of binding this vitamin. Three phenotypes controlled by two codominant autosomal alleles were identified in cattle while in water buffalo six phenotypes controlled by three codominant autosomal alleles were observed.", "contents": "Polymorphism of 14C vitamin D3 binding protein in cattle and water buffalo serum. Cattle and water buffalo sera labelled with vitamin D3[14C] (300 and 480 individual samples respectively) were subjected to starch gel electrophoresis followed by autoradiography in an attempt to identify a possible polymorphism of the proteins capable of binding this vitamin. Three phenotypes controlled by two codominant autosomal alleles were identified in cattle while in water buffalo six phenotypes controlled by three codominant autosomal alleles were observed."}
{"id": "PMID:220896", "title": "Increased proportion of active sheep erythrocyte rosette-forming lymphocytes and plasma rosette enhancement in sarcoidosis.", "content": "We examined blood lymphocyte subpopulations in 20 patients with sarcoidosis, 37 patients with other diseases, and 51 normal subjects. The B-lymphocytes were identified by the presence of surface immunoglobulin or B-lymphocyte-associated antigen. Lymphocytes were also centrifuged with sheep erythrocytes for 5 min at room temperature at 200 g, and rosette formation was assayed immediately (active E-rosette-forming T-lymphocytes) or after 60-min incubation at 4 degrees C (total T-lymphocytes). The B-lymphocytes counts did not differ among the groups. The proportions of total E-rosette-forming T-lymphocytes and active E-rosette-forming T-lymphocytes were increased in the sarcoid patients, whereas absolute counts of both types of E-rosette-forming T-lymphocytes were not different from control counts. Active E-rosette-forming T-lymphocytes showed an inverse correlation with serum concentration of angiotensin-1-converting enzyme, a probable indicator of the disease activity. Incubation of normal lymphocytes with sarcoid plasma increased the proportion of active E-rosette-forming T-lymphocytes. This plasma rosette enhancement was correlated with the number of active E-rosette-forming T-lymphocytes in the blood from which the plasma was separated. These results suggest that a factor in sarcoid plasma affects the number of active E-rosette-forming T-lymphocytes and that high numbers of these cells are associated with disease stability.", "contents": "Increased proportion of active sheep erythrocyte rosette-forming lymphocytes and plasma rosette enhancement in sarcoidosis. We examined blood lymphocyte subpopulations in 20 patients with sarcoidosis, 37 patients with other diseases, and 51 normal subjects. The B-lymphocytes were identified by the presence of surface immunoglobulin or B-lymphocyte-associated antigen. Lymphocytes were also centrifuged with sheep erythrocytes for 5 min at room temperature at 200 g, and rosette formation was assayed immediately (active E-rosette-forming T-lymphocytes) or after 60-min incubation at 4 degrees C (total T-lymphocytes). The B-lymphocytes counts did not differ among the groups. The proportions of total E-rosette-forming T-lymphocytes and active E-rosette-forming T-lymphocytes were increased in the sarcoid patients, whereas absolute counts of both types of E-rosette-forming T-lymphocytes were not different from control counts. Active E-rosette-forming T-lymphocytes showed an inverse correlation with serum concentration of angiotensin-1-converting enzyme, a probable indicator of the disease activity. Incubation of normal lymphocytes with sarcoid plasma increased the proportion of active E-rosette-forming T-lymphocytes. This plasma rosette enhancement was correlated with the number of active E-rosette-forming T-lymphocytes in the blood from which the plasma was separated. These results suggest that a factor in sarcoid plasma affects the number of active E-rosette-forming T-lymphocytes and that high numbers of these cells are associated with disease stability."}
{"id": "PMID:220897", "title": "Impairment of isoproterenol, H2 histamine, and prostaglandin E1 response of human granulocytes after incubation in vitro with live influenza vaccines.", "content": "The release of the lysosomal enzyme beta-glucuronidase from granulocytes follows incubation in vitro with complement-activated zymosan particles. Release of beta-glucuronidase is inhibited by isoproterenol, histamine, and prostaglandin E1. This in vitro model was used to study the effect of incubating a live, bivalent (A + B) influenza vaccine on the granulocyte response to the agonists described. After incubation in vitro with the live, bivalent influenza vaccine, there was a significantly impaired granulocyte reponse to all 3 agonists. The change in the response of polymorphonuclear leukocytes to isoproterenol was similar to an impairment in beta-adrenergic response found during respiratory infections in vivo. The viral-induced changes in the granulocyte response to isoproterenol may reflect similar alteration in other tissues, such as variable control of the airways and provide one explanation for the occurrence of airway dysfunction during respiratory infections.", "contents": "Impairment of isoproterenol, H2 histamine, and prostaglandin E1 response of human granulocytes after incubation in vitro with live influenza vaccines. The release of the lysosomal enzyme beta-glucuronidase from granulocytes follows incubation in vitro with complement-activated zymosan particles. Release of beta-glucuronidase is inhibited by isoproterenol, histamine, and prostaglandin E1. This in vitro model was used to study the effect of incubating a live, bivalent (A + B) influenza vaccine on the granulocyte response to the agonists described. After incubation in vitro with the live, bivalent influenza vaccine, there was a significantly impaired granulocyte reponse to all 3 agonists. The change in the response of polymorphonuclear leukocytes to isoproterenol was similar to an impairment in beta-adrenergic response found during respiratory infections in vivo. The viral-induced changes in the granulocyte response to isoproterenol may reflect similar alteration in other tissues, such as variable control of the airways and provide one explanation for the occurrence of airway dysfunction during respiratory infections."}
{"id": "PMID:220898", "title": "Hormone-mediated watery diarrhea in a family with multiple endocrine neoplasms.", "content": "A father and son each presented with severe watery diarrhea. The son was found to have a pancreatic islet-cell tumor associated with the pancreatic cholera syndrome, as well as a parathyroid adenoma. The father was found to have multiple islet-cell adenomas and the Zollinger-Ellison syndrome. Pancreatic tumor tissue from each patient contained detectable gastrin and vasoactive intestinal peptide; however, a much higher gastrin concentration was found in the tumor tissue from the father and a much higher vasoactive intestinal peptide content in the tumor tissue from the son. Thus, watery diarrhea may be mediated by different hormones in families having multiple endocrine neoplasia; the precise cause of the diarrheal syndrome should be defined to ensure the proper therapy.", "contents": "Hormone-mediated watery diarrhea in a family with multiple endocrine neoplasms. A father and son each presented with severe watery diarrhea. The son was found to have a pancreatic islet-cell tumor associated with the pancreatic cholera syndrome, as well as a parathyroid adenoma. The father was found to have multiple islet-cell adenomas and the Zollinger-Ellison syndrome. Pancreatic tumor tissue from each patient contained detectable gastrin and vasoactive intestinal peptide; however, a much higher gastrin concentration was found in the tumor tissue from the father and a much higher vasoactive intestinal peptide content in the tumor tissue from the son. Thus, watery diarrhea may be mediated by different hormones in families having multiple endocrine neoplasia; the precise cause of the diarrheal syndrome should be defined to ensure the proper therapy."}
{"id": "PMID:220900", "title": "[Nutritional and biological experiences on low-erucic acid rapeseed oil \"Janpol\". Studies on rats after ingestion of \"Janpol\" oil and other edible fats].", "content": "Comprehensive investigations were carried out for establishing the biological and nutritional value of low erucic-acid rapeseed oil from a variety of rape called Janpol selected in Poland. The pathophysiological effects of Janpol rapeseed oil were observed after giving it as the only source of fat in the diet or added in different proportions to other edible fats. In all cases the total amount of fat in the diet was 20 p. 100 kcal. The investigations were carried out on 78 young male Wistar rats aged 25 days at the beginning of the experiment. The rats were divided into 7 groups and they were given diets containing: 1) soybean oil; 2) mixed fats; 3) rapeseed oil of high erucic-acid content; 4) mixed fats containing 25 p. 100 of Janpol rapeseed oil; 5) mixed fats with 50 p. 100 of Janpol rapeseed oil; 6) mixed fats with 75 p. 100 of Janpol rapeseed oil; 7) Janpol rapeseed oil only. The experiment lasted 3 months. After its completion the rats were decapitated after 18 hours of starvation. The investigation s included : determination of weight gain, determination of the weight of selected organs (liver-lungs, heart, kidneys, testes, spleen), determination of alkaline phosphatase and pseudocholinesterase activity in the serum, determination of triglycerides and cholesterol in the serum, tests for adrenocortical function, histo-chemical investigations of the liver (alkaline and acid phosphatase, adenosine triphosphatase, fatty infiltration of the liver), macroscopic and microscopic anatomopathological examinations. The authors found the Janpol rapeseed oil caused less pronounced changes in the determined indices of the biological and nutritional evaluation as compared with high-erucic-acid rapeseed oil. Janpol repeseed oil given to experimental animals mixed with other fats in proportions of 25 p. 100 and 50 p. 100 of all fats in the diet, that is 5 p. 100 and 10 p. 100 kcal in the diet derived from Janpol oil gave in most determinations of the investigated parameters results very similar to those observed in animals receiving soybean oil. The results of these investigations show that Janpol rapesed oil can be used for nutrition of man in amounts not exceeding 10 p. 100 of the total caloric content of food.", "contents": "[Nutritional and biological experiences on low-erucic acid rapeseed oil \"Janpol\". Studies on rats after ingestion of \"Janpol\" oil and other edible fats]. Comprehensive investigations were carried out for establishing the biological and nutritional value of low erucic-acid rapeseed oil from a variety of rape called Janpol selected in Poland. The pathophysiological effects of Janpol rapeseed oil were observed after giving it as the only source of fat in the diet or added in different proportions to other edible fats. In all cases the total amount of fat in the diet was 20 p. 100 kcal. The investigations were carried out on 78 young male Wistar rats aged 25 days at the beginning of the experiment. The rats were divided into 7 groups and they were given diets containing: 1) soybean oil; 2) mixed fats; 3) rapeseed oil of high erucic-acid content; 4) mixed fats containing 25 p. 100 of Janpol rapeseed oil; 5) mixed fats with 50 p. 100 of Janpol rapeseed oil; 6) mixed fats with 75 p. 100 of Janpol rapeseed oil; 7) Janpol rapeseed oil only. The experiment lasted 3 months. After its completion the rats were decapitated after 18 hours of starvation. The investigation s included : determination of weight gain, determination of the weight of selected organs (liver-lungs, heart, kidneys, testes, spleen), determination of alkaline phosphatase and pseudocholinesterase activity in the serum, determination of triglycerides and cholesterol in the serum, tests for adrenocortical function, histo-chemical investigations of the liver (alkaline and acid phosphatase, adenosine triphosphatase, fatty infiltration of the liver), macroscopic and microscopic anatomopathological examinations. The authors found the Janpol rapeseed oil caused less pronounced changes in the determined indices of the biological and nutritional evaluation as compared with high-erucic-acid rapeseed oil. Janpol repeseed oil given to experimental animals mixed with other fats in proportions of 25 p. 100 and 50 p. 100 of all fats in the diet, that is 5 p. 100 and 10 p. 100 kcal in the diet derived from Janpol oil gave in most determinations of the investigated parameters results very similar to those observed in animals receiving soybean oil. The results of these investigations show that Janpol rapesed oil can be used for nutrition of man in amounts not exceeding 10 p. 100 of the total caloric content of food."}
{"id": "PMID:220903", "title": "Effect of phenytoin on bone and vitamin D metabolism.", "content": "Calcium and vitamin D metabolism were evaluated in 5 adult epileptic patients before and during treatment with phenytoin. Significant decreases occurred in serum concentrations of calcium, albumin, and 25-hydroxy-cholecalciferol. The decreases in serum calcium paralleled those in serum albumin. Significant increases occurred in serum alkaline phosphatase and 1 alpha, 25-dihydroxycholecalciferol, in urinary hydroxyproline, and in the fractional gastrointestinal absorption of calcium. Urinary cyclic adenosine monophosphate and serum parathyroid hormone did not change. The results suggest that the bone disease resulting from phenytoin therapy may be associated with a deficiency of 25-hydroxycholecalciferol and not of 1 alpha, 25-dihydroxycholecalciferol, and that reduced gastrointestinal absorption of calcium or changes in parathyroid function may not be necessary for the development of bone disease.", "contents": "Effect of phenytoin on bone and vitamin D metabolism. Calcium and vitamin D metabolism were evaluated in 5 adult epileptic patients before and during treatment with phenytoin. Significant decreases occurred in serum concentrations of calcium, albumin, and 25-hydroxy-cholecalciferol. The decreases in serum calcium paralleled those in serum albumin. Significant increases occurred in serum alkaline phosphatase and 1 alpha, 25-dihydroxycholecalciferol, in urinary hydroxyproline, and in the fractional gastrointestinal absorption of calcium. Urinary cyclic adenosine monophosphate and serum parathyroid hormone did not change. The results suggest that the bone disease resulting from phenytoin therapy may be associated with a deficiency of 25-hydroxycholecalciferol and not of 1 alpha, 25-dihydroxycholecalciferol, and that reduced gastrointestinal absorption of calcium or changes in parathyroid function may not be necessary for the development of bone disease."}
{"id": "PMID:220905", "title": "[New amino acid from the antibiotic, ristomycin A].", "content": "A new amino acid E was isolated from a mixture of the products of the reductive hydrolysis of ristomycin A 57% HJ in the presence of red phosphorus. Its characterization was performed. The new amino acid was formed as a result of reductive dehydration of the respective beta-oxyamino acid present in the native antibiotic and being completely destroyed during general acid or alkaline hydrolysis.", "contents": "[New amino acid from the antibiotic, ristomycin A]. A new amino acid E was isolated from a mixture of the products of the reductive hydrolysis of ristomycin A 57% HJ in the presence of red phosphorus. Its characterization was performed. The new amino acid was formed as a result of reductive dehydration of the respective beta-oxyamino acid present in the native antibiotic and being completely destroyed during general acid or alkaline hydrolysis."}
{"id": "PMID:220901", "title": "Experimental viral infections of the inner ear. II. Simian virus 40 induced tumors of the temporal bone.", "content": "Pathological and virological studies were performed on temporal bones of 23 hamsters which developed tumors subsequent to neonatal inoculation of simian virus 40 (SV40). Four to five months after viral inoculation, 22 hamsters developed undifferentiated sarcomas in the subcutaneous space adjacent to the temporal bone. Nine tumors invaded the temporal bone, occassionally extending to the subarachnoid space but not to the inner ear. Choroid plexus papillomas developed in four animals, with one tumor demonstrating invasion of the cochlear aqueduct, internal auditory canal, and cochlear modiolus. Cells grown from a sarcoma and a choroid plexus papilloma contained tumor antigen and established that the tumors were SV40 virus induced.", "contents": "Experimental viral infections of the inner ear. II. Simian virus 40 induced tumors of the temporal bone. Pathological and virological studies were performed on temporal bones of 23 hamsters which developed tumors subsequent to neonatal inoculation of simian virus 40 (SV40). Four to five months after viral inoculation, 22 hamsters developed undifferentiated sarcomas in the subcutaneous space adjacent to the temporal bone. Nine tumors invaded the temporal bone, occassionally extending to the subarachnoid space but not to the inner ear. Choroid plexus papillomas developed in four animals, with one tumor demonstrating invasion of the cochlear aqueduct, internal auditory canal, and cochlear modiolus. Cells grown from a sarcoma and a choroid plexus papilloma contained tumor antigen and established that the tumors were SV40 virus induced."}
{"id": "PMID:220906", "title": "[Experimental study of the action of the RNAse from Actinomyces rimosus on the variolovaccine virus].", "content": "The effect of Actinomyces rimosus RNAase on the variolovaccine virus was studied. The inhibitory effect of the Actinomyces rimosus RNAase on the variolovaccine virus reproduction in the tissue culture cells was shown. In the experiments with the use of chick embryons and rabbits this effect was less pronounced. A 10 time increase in the infection multiplicity both in the tissue culture and the chick embryons had no noticeable effect on the level of the virus inhibition. It was supposed that the inhibitory effect of the RNAase on the variolovaccine was associated with impairment of the cell metabolism.", "contents": "[Experimental study of the action of the RNAse from Actinomyces rimosus on the variolovaccine virus]. The effect of Actinomyces rimosus RNAase on the variolovaccine virus was studied. The inhibitory effect of the Actinomyces rimosus RNAase on the variolovaccine virus reproduction in the tissue culture cells was shown. In the experiments with the use of chick embryons and rabbits this effect was less pronounced. A 10 time increase in the infection multiplicity both in the tissue culture and the chick embryons had no noticeable effect on the level of the virus inhibition. It was supposed that the inhibitory effect of the RNAase on the variolovaccine was associated with impairment of the cell metabolism."}
{"id": "PMID:220907", "title": "[Effect of dibasol and ascorbic acid on the antiviral activity of human interferon in cell culture].", "content": "The antiviral effect of human lymphocytic interferon was studied in the primary culture of human embryonic fibroblasts in the presence of dibazol and ascorbic acid. It was found that dibazol and ascorbic acid in concentrations of 5 and 10 gamma/ml respectively were capable of increasing the antiviral effect of human interferon in homological cells. The assays of 13 lots of interferon showed that its average titer in the experiments with ascorbic acid was 2.5 times higher than that in the control. The assays of 21 lots of interferon showed that its average titer in the experiments with dibazol was 3 times higher than that in the control. It is suggested that an increase in the protective properties of interferon in the presence of dibazol and ascorbic acid is connected with their capacity for stimulating the intracellular production of DNA and protein. The data obtained indicate that dibazol and ascorbic acid may be recommended in the complex of therapy and prophylaxis of antiviral infections.", "contents": "[Effect of dibasol and ascorbic acid on the antiviral activity of human interferon in cell culture]. The antiviral effect of human lymphocytic interferon was studied in the primary culture of human embryonic fibroblasts in the presence of dibazol and ascorbic acid. It was found that dibazol and ascorbic acid in concentrations of 5 and 10 gamma/ml respectively were capable of increasing the antiviral effect of human interferon in homological cells. The assays of 13 lots of interferon showed that its average titer in the experiments with ascorbic acid was 2.5 times higher than that in the control. The assays of 21 lots of interferon showed that its average titer in the experiments with dibazol was 3 times higher than that in the control. It is suggested that an increase in the protective properties of interferon in the presence of dibazol and ascorbic acid is connected with their capacity for stimulating the intracellular production of DNA and protein. The data obtained indicate that dibazol and ascorbic acid may be recommended in the complex of therapy and prophylaxis of antiviral infections."}
{"id": "PMID:220908", "title": "[Antiviral activity of interferon and its inducers in human lymphoblastoid and somatic cells].", "content": "The antiviral effect of interferon inductors, such as poly-I--poly-C, phage f2 RNA replicative form and low molecular inductor GSN and their influence on cellular DNA synthesis were studied in the cultures of lymphoblastoid (inplanting lines Raji Namalva) and somatic human cells. The Semliki forest virus used as the test organism multiplicated well in cells Raji accumulating up to 9 lg BOU/ml. The two-strand RNA was less active in the lymphoid cells than in the somatic ones. GSN was 10 times more active and less toxic in cells Raji as compared to the fibroblasts. The lymphoblastoid interferon had higher antiviral activity as compared to the fibroblast interferon in the system of Raji--Semliki forest virus than in the system of the human embryon fibroblast--Venezuela Horse Encephalytic Virus. Romantadin actively inhibited (100 times) production of the alfavirus in both the somatic and lymphoblastoid cells.", "contents": "[Antiviral activity of interferon and its inducers in human lymphoblastoid and somatic cells]. The antiviral effect of interferon inductors, such as poly-I--poly-C, phage f2 RNA replicative form and low molecular inductor GSN and their influence on cellular DNA synthesis were studied in the cultures of lymphoblastoid (inplanting lines Raji Namalva) and somatic human cells. The Semliki forest virus used as the test organism multiplicated well in cells Raji accumulating up to 9 lg BOU/ml. The two-strand RNA was less active in the lymphoid cells than in the somatic ones. GSN was 10 times more active and less toxic in cells Raji as compared to the fibroblasts. The lymphoblastoid interferon had higher antiviral activity as compared to the fibroblast interferon in the system of Raji--Semliki forest virus than in the system of the human embryon fibroblast--Venezuela Horse Encephalytic Virus. Romantadin actively inhibited (100 times) production of the alfavirus in both the somatic and lymphoblastoid cells."}
{"id": "PMID:220909", "title": "[Determination of a dimethylaniline mixture in the intermediate products for the production of semisynthetic penicillins].", "content": "A gas-chromatographic method for determination fo the content of dimethylaniline (DMA) in 6-aminopenicillanic acid, a semi-product for production of semi-synthetic antibiotics, was elaborated. The chloroform extracts of DMA from the alkaline solutions of the preparation were analysed in a gas chromatograph with a flame-ionization detector on a stainless steel column 2 m long and the inner diameter of 2 mm filled with 10 per cent OV-17 on chromosorb W-HMDS at a temperature of 112 degrees C. The minimum detectable amount of DMA was 5.10(-9) g. The assay error was +/- 5.35 per cent. The method may be used for the assay of other semi-synthetic antibiotics.", "contents": "[Determination of a dimethylaniline mixture in the intermediate products for the production of semisynthetic penicillins]. A gas-chromatographic method for determination fo the content of dimethylaniline (DMA) in 6-aminopenicillanic acid, a semi-product for production of semi-synthetic antibiotics, was elaborated. The chloroform extracts of DMA from the alkaline solutions of the preparation were analysed in a gas chromatograph with a flame-ionization detector on a stainless steel column 2 m long and the inner diameter of 2 mm filled with 10 per cent OV-17 on chromosorb W-HMDS at a temperature of 112 degrees C. The minimum detectable amount of DMA was 5.10(-9) g. The assay error was +/- 5.35 per cent. The method may be used for the assay of other semi-synthetic antibiotics."}
{"id": "PMID:220921", "title": "Localization of viral DNA-replication in sections of human warts by nucleic acid hybridization with complementary RNA of human papilloma virus Type 1.", "content": "Using complementary RNA of human papilloma virus type 1 (HPV1) and in situ hybridization techniques the localization of viral DNA replication was studied in sections of 38 human virus acanthomata from 31 different patients. In five cases significant labeling was detected by autoradiography. Labeling started always in the first or the second suprabasal cell layer and was strongly limited to the nuclei. A remarkable early beginning of the vacuolated process seemed to be correlated with the visible DNA replication. No labeling could be detected in the basal cell layer. This suggests that these cells contain at the most only a small number of viral genomes. Our findings represent only the situation in human warts definitely caused by HPV 1. We are not able to say, whether our negative hybridization results in the remaining warts indicate either the scarcity of viral genomes within these sections or their infection by a different agent.", "contents": "Localization of viral DNA-replication in sections of human warts by nucleic acid hybridization with complementary RNA of human papilloma virus Type 1. Using complementary RNA of human papilloma virus type 1 (HPV1) and in situ hybridization techniques the localization of viral DNA replication was studied in sections of 38 human virus acanthomata from 31 different patients. In five cases significant labeling was detected by autoradiography. Labeling started always in the first or the second suprabasal cell layer and was strongly limited to the nuclei. A remarkable early beginning of the vacuolated process seemed to be correlated with the visible DNA replication. No labeling could be detected in the basal cell layer. This suggests that these cells contain at the most only a small number of viral genomes. Our findings represent only the situation in human warts definitely caused by HPV 1. We are not able to say, whether our negative hybridization results in the remaining warts indicate either the scarcity of viral genomes within these sections or their infection by a different agent."}
{"id": "PMID:220922", "title": "[Gonadoblastoma and overgrowing dysgerminoma in Turner mosaicism [45, XO/46, Xi (Xq)] (author's transl)].", "content": "It is well established that the Y-chromosome is associated with germ cell tumor development. There is a considerable tumour risk in XY- and XY/XO-gonadal dysgenesis. In the absence of Y-chromosome germ cell tumours are extremely rare. The history of a patient with 45 XO/46 Xi (Xq)-karyotype is presented, who had a gonadoblastoma with overgrowing dysgerminoma. According to basal body temperature recordings, this patient ovulated up to the age of 22 years. After this cyclical ovarian function was exhausted; histologically no primordial follicles could be detected. Gonadotropin as well as prolactin binding sites in the tumours could not be demonstrated, suggesting hormone independency and complete malignant transformation of the tumor. In general the clinician should be aware of a possible germ cell tumour development in the absence of a Y-chromosome. However as far as the clinical management of patients with dysgenetic gonads is concerned, prophylactic gonadectomy is only indicated in the presence of a Y-chromosome.", "contents": "[Gonadoblastoma and overgrowing dysgerminoma in Turner mosaicism [45, XO/46, Xi (Xq)] (author's transl)]. It is well established that the Y-chromosome is associated with germ cell tumor development. There is a considerable tumour risk in XY- and XY/XO-gonadal dysgenesis. In the absence of Y-chromosome germ cell tumours are extremely rare. The history of a patient with 45 XO/46 Xi (Xq)-karyotype is presented, who had a gonadoblastoma with overgrowing dysgerminoma. According to basal body temperature recordings, this patient ovulated up to the age of 22 years. After this cyclical ovarian function was exhausted; histologically no primordial follicles could be detected. Gonadotropin as well as prolactin binding sites in the tumours could not be demonstrated, suggesting hormone independency and complete malignant transformation of the tumor. In general the clinician should be aware of a possible germ cell tumour development in the absence of a Y-chromosome. However as far as the clinical management of patients with dysgenetic gonads is concerned, prophylactic gonadectomy is only indicated in the presence of a Y-chromosome."}
{"id": "PMID:220924", "title": "Intranuclear inclusion bodies in epithelial cells of human vas deferens.", "content": "Four different types of inclusion bodies were seen within the nucleus of the principal cells in segments of vas deferens from 40 fertile males: (1) electron-dense homogeneous bodies of various sizes (0.1--1.8 microns) and shapes, (2) granular bodies approximately 0.06--0.12 microns, (3) lipid inclusion bodies, and (4) less electron-dense, filamentous bodies. They were either membrane-bound or free within the nucleoplasm. Some membranous material was scattered within the nucleoplasm. The internal structure of nuclei containing these bodies differed from cell to cell. The nucleoplasm was composed either of dense granular elements or fine filamentous components. The aggregation and density of the ground nuclear material increased with increasing numbers of inclusion bodies. Very dense nuclei were in cells with typical features of degeneration. Frequently, extruded parts of cells or entire cells were seen within the lumen of the vas deferens.", "contents": "Intranuclear inclusion bodies in epithelial cells of human vas deferens. Four different types of inclusion bodies were seen within the nucleus of the principal cells in segments of vas deferens from 40 fertile males: (1) electron-dense homogeneous bodies of various sizes (0.1--1.8 microns) and shapes, (2) granular bodies approximately 0.06--0.12 microns, (3) lipid inclusion bodies, and (4) less electron-dense, filamentous bodies. They were either membrane-bound or free within the nucleoplasm. Some membranous material was scattered within the nucleoplasm. The internal structure of nuclei containing these bodies differed from cell to cell. The nucleoplasm was composed either of dense granular elements or fine filamentous components. The aggregation and density of the ground nuclear material increased with increasing numbers of inclusion bodies. Very dense nuclei were in cells with typical features of degeneration. Frequently, extruded parts of cells or entire cells were seen within the lumen of the vas deferens."}
{"id": "PMID:220925", "title": "Metastasis-induced acute pancreatitis in small cell bronchogenic carcinoma.", "content": "Despite frequent metastatic involvement of the pancreas at postmortem examination in patients with small cell lung cancer, clinically observed pancreatitis due to metastatic pancreatic tumor rarely has been reported. This communication describes three cases of clinical acute pancreatitis occurring in a consecutive series of 40 patients with oat cell lung cancer. This complication may appear either as the initial manifestation of the neoplasm or during a recrudescent phase of the malignant growth. The diagnosis should be suspected in the presence of the clinical, laboratory, and radiologic features of acute pancreatitis in patients with known small cell carcinoma of the lung, especially if there is evidence of progression of the neoplastic disease elsewhere and no response to conservative medical management. Aggressive treatment with polychemotherapy can produce rapid clinical improvement and useful prolongation of survival.", "contents": "Metastasis-induced acute pancreatitis in small cell bronchogenic carcinoma. Despite frequent metastatic involvement of the pancreas at postmortem examination in patients with small cell lung cancer, clinically observed pancreatitis due to metastatic pancreatic tumor rarely has been reported. This communication describes three cases of clinical acute pancreatitis occurring in a consecutive series of 40 patients with oat cell lung cancer. This complication may appear either as the initial manifestation of the neoplasm or during a recrudescent phase of the malignant growth. The diagnosis should be suspected in the presence of the clinical, laboratory, and radiologic features of acute pancreatitis in patients with known small cell carcinoma of the lung, especially if there is evidence of progression of the neoplastic disease elsewhere and no response to conservative medical management. Aggressive treatment with polychemotherapy can produce rapid clinical improvement and useful prolongation of survival."}
{"id": "PMID:220926", "title": "[Complex bone abnormalities with fatal outcome: a new familial syndrome].", "content": "A new lethal disorder affecting two brothers is described. The features were curvature of the long bones, multiple fractures, dysmorphic facies, syndactyly and absence of ossification in the cranial vault. The condition could be inherited as an autosomal recessive or sex linked condition.", "contents": "[Complex bone abnormalities with fatal outcome: a new familial syndrome]. A new lethal disorder affecting two brothers is described. The features were curvature of the long bones, multiple fractures, dysmorphic facies, syndactyly and absence of ossification in the cranial vault. The condition could be inherited as an autosomal recessive or sex linked condition."}
{"id": "PMID:220927", "title": "BLV-LB virus-specific sequences in cattle with spontaneous and experimentally induced leukemia.", "content": "Poly(A)-containing RNAs were extracted directly from the culture fluid of BLV-producing continuous and short-term lymphocyte cultures. The abovesaid poly(A)-RNAs were used as a template to synthesize complementary [3H]DNA (BLV cDNA). BLV cDNA possessed a high degree of homology to poly(A)-RNA isolated directly from the blood plasma of a leukemic animal. In contrast of leukemic cattle BLV-related sequences in white blood cells of normal animals were absent. Leukemic cells of cattle with both, spontaneous and experimentally induced leukemia contained bovine leukemia virus sequences in their genomes.", "contents": "BLV-LB virus-specific sequences in cattle with spontaneous and experimentally induced leukemia. Poly(A)-containing RNAs were extracted directly from the culture fluid of BLV-producing continuous and short-term lymphocyte cultures. The abovesaid poly(A)-RNAs were used as a template to synthesize complementary [3H]DNA (BLV cDNA). BLV cDNA possessed a high degree of homology to poly(A)-RNA isolated directly from the blood plasma of a leukemic animal. In contrast of leukemic cattle BLV-related sequences in white blood cells of normal animals were absent. Leukemic cells of cattle with both, spontaneous and experimentally induced leukemia contained bovine leukemia virus sequences in their genomes."}
{"id": "PMID:220928", "title": "[The effect of ethylnitrosourea in the activity of the NAD-linked glycero-3-phosphate dehydrogenase in the Vth nerve of developing rats and its relation to myelination and tumour induction (author's transl)].", "content": "The activity of NAD-linked L-alpha-glycero-3-phosphate dehydrogenase (E.C. 1.1.1.8.) in the Vth nerve from albino rats treated with a single subcutaneous injection of ethylnitrosourea in the first day of life and from controls was determined biochemically in 10 different age groups ranging from 7 to 70 days. The specific activities of the controls rise rapidly from the 7--35 days of life and remain there after almost at the same level. The activity of the ENU treated animals is significantly lower than that of the controls and reaches only at the age of 63 days the values of the 35 days old untreated animals. About 26% of the activity values of the treated animals are below the lower confidence limit of the controls.", "contents": "[The effect of ethylnitrosourea in the activity of the NAD-linked glycero-3-phosphate dehydrogenase in the Vth nerve of developing rats and its relation to myelination and tumour induction (author's transl)]. The activity of NAD-linked L-alpha-glycero-3-phosphate dehydrogenase (E.C. 1.1.1.8.) in the Vth nerve from albino rats treated with a single subcutaneous injection of ethylnitrosourea in the first day of life and from controls was determined biochemically in 10 different age groups ranging from 7 to 70 days. The specific activities of the controls rise rapidly from the 7--35 days of life and remain there after almost at the same level. The activity of the ENU treated animals is significantly lower than that of the controls and reaches only at the age of 63 days the values of the 35 days old untreated animals. About 26% of the activity values of the treated animals are below the lower confidence limit of the controls."}
{"id": "PMID:220929", "title": "Ultrastructural changes in rat liver cells induced by Proteus mirabilis endotoxin.", "content": "Changes in individual organella of rat hepatocytes developing under the effect of Proteus mirabilis endotoxin (Pme) were observed under electron microscope. The effect of drugs which diminish liver cell injury by Pme (polymyxin, cholestyramine and hydrocortisone) on the changes was studied.", "contents": "Ultrastructural changes in rat liver cells induced by Proteus mirabilis endotoxin. Changes in individual organella of rat hepatocytes developing under the effect of Proteus mirabilis endotoxin (Pme) were observed under electron microscope. The effect of drugs which diminish liver cell injury by Pme (polymyxin, cholestyramine and hydrocortisone) on the changes was studied."}
{"id": "PMID:220930", "title": "Serological identification of viral and virus-related antigens on DBA/2 mouse leukemia lymphocytes.", "content": "Allogenic, semisyngeneic and syngeneic sera of animals immunized with ML-positive leukemia L1210 cells, besides anti-ML antibodies, contain antibodies which react with Gross cellular surface antigen. ML antigen and Gross cellular surface antigen were shown by the immunoferritin test in electron microscopy, and by the blocking test, to be situated on different parts of the cell surface. No budding viral particles were found on the areas occupied by these antigens. By distinguishing the ML antigen identified on the surface of leukemia L1210 cells from the Gross cellular antigen, it was shown that the MTV present in leukemias of DBA/2 mice has no leukemogenic properties. Demonstration of core and envelope antigens of the MTV and Gross MuLV, besides C particles and intracytoplasmatic A particles, which are precursors of B particles, is proof of existence of genomes of both viruses in leukemia L1210 cells. The ability of leukemia L1210 cells to absorb activity from the anti-ML sera and reaction between anti-ML sera and isolated B particles of the MTV in immunoprecipitation, indicate probable existence of an antigenic component of the MTV within the ML antigen.", "contents": "Serological identification of viral and virus-related antigens on DBA/2 mouse leukemia lymphocytes. Allogenic, semisyngeneic and syngeneic sera of animals immunized with ML-positive leukemia L1210 cells, besides anti-ML antibodies, contain antibodies which react with Gross cellular surface antigen. ML antigen and Gross cellular surface antigen were shown by the immunoferritin test in electron microscopy, and by the blocking test, to be situated on different parts of the cell surface. No budding viral particles were found on the areas occupied by these antigens. By distinguishing the ML antigen identified on the surface of leukemia L1210 cells from the Gross cellular antigen, it was shown that the MTV present in leukemias of DBA/2 mice has no leukemogenic properties. Demonstration of core and envelope antigens of the MTV and Gross MuLV, besides C particles and intracytoplasmatic A particles, which are precursors of B particles, is proof of existence of genomes of both viruses in leukemia L1210 cells. The ability of leukemia L1210 cells to absorb activity from the anti-ML sera and reaction between anti-ML sera and isolated B particles of the MTV in immunoprecipitation, indicate probable existence of an antigenic component of the MTV within the ML antigen."}
{"id": "PMID:220931", "title": "The influence of immunization of Syrian hamsters with tumor cells treated with glutaraldehyde on transplantation immunity and the cytotoxic effect of lymphocytes on polyoma tumor cells.", "content": "The influence of glutaraldehyde on polyoma tumor cells was studied in syngeneic Syrian hamsters, which were inoculated with glutarldhehyde-treated cells. Sera from carriers of the tumor, immunized hamsters and healthy animals inhibited in vitro cytotoxicity of sensitized lymphocytes (spleen cells) for tumor cells. If healthy animals were inoculated subcutaneously with spleen cells from immunized hamsters together with tumor cells, tumor growth was inhibited (in Winn's test) compared with animals not so inoculated and recieving only tumor cells. Cells taking part in immune responses to hamster membrane antigens were demonstrated in vitro by the microcytotoxic test. Lymphocytes from hamsters immunized with polyoma tumor cells fixed with glutaraldehyde against polyoma tumor cells were cytotoxic for target cells provided the ratio of attacking to target cells was 50:1 or higher.", "contents": "The influence of immunization of Syrian hamsters with tumor cells treated with glutaraldehyde on transplantation immunity and the cytotoxic effect of lymphocytes on polyoma tumor cells. The influence of glutaraldehyde on polyoma tumor cells was studied in syngeneic Syrian hamsters, which were inoculated with glutarldhehyde-treated cells. Sera from carriers of the tumor, immunized hamsters and healthy animals inhibited in vitro cytotoxicity of sensitized lymphocytes (spleen cells) for tumor cells. If healthy animals were inoculated subcutaneously with spleen cells from immunized hamsters together with tumor cells, tumor growth was inhibited (in Winn's test) compared with animals not so inoculated and recieving only tumor cells. Cells taking part in immune responses to hamster membrane antigens were demonstrated in vitro by the microcytotoxic test. Lymphocytes from hamsters immunized with polyoma tumor cells fixed with glutaraldehyde against polyoma tumor cells were cytotoxic for target cells provided the ratio of attacking to target cells was 50:1 or higher."}
{"id": "PMID:220932", "title": "Rat interferons. VI. Heterologous interferon in the treatment of viral infections.", "content": "In previous studies in vitro we demonstrated the protection of mouse cells against viral infections by rat interferon. In continuation, the present paper reports results of a study designed to confirm this heterospecific activity of rat interferon in vivo. Experiments were carried out with mice of the inbred 129/AoBoy strain, inoculated intranasally or intraperitoneally with EMC-strain Col MM, VSV and influenza A 055/74 viruses, and treated with mouse or rat interferon administered by the same routes as infection. Both interferons exhibited protective action. The therapeutic effect of the mouse and rat interferons was dependent on the infecting dose of the viruses. Rat interferon proved more effective in the treatment of mice infected intraperitoneally than mice infected intranasally.", "contents": "Rat interferons. VI. Heterologous interferon in the treatment of viral infections. In previous studies in vitro we demonstrated the protection of mouse cells against viral infections by rat interferon. In continuation, the present paper reports results of a study designed to confirm this heterospecific activity of rat interferon in vivo. Experiments were carried out with mice of the inbred 129/AoBoy strain, inoculated intranasally or intraperitoneally with EMC-strain Col MM, VSV and influenza A 055/74 viruses, and treated with mouse or rat interferon administered by the same routes as infection. Both interferons exhibited protective action. The therapeutic effect of the mouse and rat interferons was dependent on the infecting dose of the viruses. Rat interferon proved more effective in the treatment of mice infected intraperitoneally than mice infected intranasally."}
{"id": "PMID:220933", "title": "Pathogenesis of chronic myocarditis in mice infected with coxsackie B3 viruses.", "content": "Infection of 300 mice of the Swiss race with Coxsackie B3 viruses gave rise to chronic myocarditis and endocarditis. The virus was cultured from the heart muscle 9 days post infection. Between days 18 and 108 post infection, virtually all mice showed evidence of an active inflammatory process in the myocardium, and in one half there was proliferation of endothelial cells, and infitration and fibrosis in the endocardium. Immunomorphologic studies demonstrated the precence of antiheart antibodies in the blood serum, and Coxsackie B3 antigen and immunoglobulin deposits in the myocardium and endocardium. Highest levels of antivirus antibodies were observed 18 days post infection.", "contents": "Pathogenesis of chronic myocarditis in mice infected with coxsackie B3 viruses. Infection of 300 mice of the Swiss race with Coxsackie B3 viruses gave rise to chronic myocarditis and endocarditis. The virus was cultured from the heart muscle 9 days post infection. Between days 18 and 108 post infection, virtually all mice showed evidence of an active inflammatory process in the myocardium, and in one half there was proliferation of endothelial cells, and infitration and fibrosis in the endocardium. Immunomorphologic studies demonstrated the precence of antiheart antibodies in the blood serum, and Coxsackie B3 antigen and immunoglobulin deposits in the myocardium and endocardium. Highest levels of antivirus antibodies were observed 18 days post infection."}
{"id": "PMID:220934", "title": "Trials of treating myocarditis in mice infected with coxsackie B3 viruses.", "content": "On the assumption of an immunologic background of chronic myocarditis after infection with Coxsackie B3 viruses, mice were treated with prednisolone or cyclophosphamide, starting 18 days after infection, for periods of three months. The favorable therapeutic effect indicates that chronic myocarditis is an immunologic disease.", "contents": "Trials of treating myocarditis in mice infected with coxsackie B3 viruses. On the assumption of an immunologic background of chronic myocarditis after infection with Coxsackie B3 viruses, mice were treated with prednisolone or cyclophosphamide, starting 18 days after infection, for periods of three months. The favorable therapeutic effect indicates that chronic myocarditis is an immunologic disease."}
{"id": "PMID:220937", "title": "[Metastasis of breast carcinoma to the pituitary. Report of a case].", "content": "The case of a 65 old woman who had a rapidly progressive neurologic symtomatology is reported. The autopsy disclosed a carcinoma of the breast with metastases in brain, cerebellum, brainstem, pituitary, thyroid gland and the adrenals. The frequency of the pituitary metastases is discussed, especially in cases of breast cancer. The macro and microscopic aspects of the metastatic pituitary gland are studied.", "contents": "[Metastasis of breast carcinoma to the pituitary. Report of a case]. The case of a 65 old woman who had a rapidly progressive neurologic symtomatology is reported. The autopsy disclosed a carcinoma of the breast with metastases in brain, cerebellum, brainstem, pituitary, thyroid gland and the adrenals. The frequency of the pituitary metastases is discussed, especially in cases of breast cancer. The macro and microscopic aspects of the metastatic pituitary gland are studied."}
{"id": "PMID:220938", "title": "CSF viral antibodies. Evaluation in amyotrophic lateral sclerosis and late-onset postpoliomyelitis progressive muscular atrophy.", "content": "Serum and CSF from 48 patients with amyotrophic lateral sclerosis and six patients with late-onset postpoliomyelitis progressive muscular atrophy were investigated for the presence of antibody to poliovirus types 1, 2, and 3, coxsackie viruses B3 and B4, influenza A, measles, rubella, mumps, herpes simplex types 1 and 2, cytomegalovirus, varicella-zoster, and Toxoplasma gondii. These results were compared with those from 53 control patients with neuromuscular disease matched for age, sex, race, and poliovirus vaccine exposure. There was no difference either in distribution of serum or CSF antibody titers or the geometric-mean antibody titers. There was no evidence suggesting the presence of locally produced specific viral antibody within the CNS to any of the agents studied. In particular, there was no serological evidence to suggest an association between persistent infection with any poliovirus type and amyotrophic lateral sclerosis or late-onset postpoliomyelitis progressive muscular atrophy.", "contents": "CSF viral antibodies. Evaluation in amyotrophic lateral sclerosis and late-onset postpoliomyelitis progressive muscular atrophy. Serum and CSF from 48 patients with amyotrophic lateral sclerosis and six patients with late-onset postpoliomyelitis progressive muscular atrophy were investigated for the presence of antibody to poliovirus types 1, 2, and 3, coxsackie viruses B3 and B4, influenza A, measles, rubella, mumps, herpes simplex types 1 and 2, cytomegalovirus, varicella-zoster, and Toxoplasma gondii. These results were compared with those from 53 control patients with neuromuscular disease matched for age, sex, race, and poliovirus vaccine exposure. There was no difference either in distribution of serum or CSF antibody titers or the geometric-mean antibody titers. There was no evidence suggesting the presence of locally produced specific viral antibody within the CNS to any of the agents studied. In particular, there was no serological evidence to suggest an association between persistent infection with any poliovirus type and amyotrophic lateral sclerosis or late-onset postpoliomyelitis progressive muscular atrophy."}
{"id": "PMID:220939", "title": "Combined myelopathy and radiculoneuropathy with malignant lymphoproliferative disease.", "content": "Clinicopathological findings for two similar patients in whom myelopathy and radiculoneuropathy developed in association with malignant lymphoma were reviewed. This pattern of neurological disease has not been reported in association with the malignant lymphoproliferative disorders, and it provides ground for speculation concerning lymphocyte function and viral infection in cases of neurological disease in association with remote neoplasm.", "contents": "Combined myelopathy and radiculoneuropathy with malignant lymphoproliferative disease. Clinicopathological findings for two similar patients in whom myelopathy and radiculoneuropathy developed in association with malignant lymphoma were reviewed. This pattern of neurological disease has not been reported in association with the malignant lymphoproliferative disorders, and it provides ground for speculation concerning lymphocyte function and viral infection in cases of neurological disease in association with remote neoplasm."}
{"id": "PMID:220940", "title": "[Cyclic GMP in the eye and its correlation with externally administered insulin].", "content": "Experiments carried on Albino rabbits for detecting cyclic GMP in the eye tissues and to observe whether cGMP is influenced through local administration of insulin to the eye, externally. Whereas, for instance, intraveinous administration of insulin does not influence, in any way, concentration of cGMP -- after 3' to 10' -- in the humour aqueous, the lens, the vitreous body and the blood serum, following administration of insulin by means of retrobulbar injection, for the same time and on the same tissues, the values of cGMP appear increased. On the other hand, results yielded by our experiments allow us to estimate that environment preparing cGMP in the eye is the retina and the choroid.", "contents": "[Cyclic GMP in the eye and its correlation with externally administered insulin]. Experiments carried on Albino rabbits for detecting cyclic GMP in the eye tissues and to observe whether cGMP is influenced through local administration of insulin to the eye, externally. Whereas, for instance, intraveinous administration of insulin does not influence, in any way, concentration of cGMP -- after 3' to 10' -- in the humour aqueous, the lens, the vitreous body and the blood serum, following administration of insulin by means of retrobulbar injection, for the same time and on the same tissues, the values of cGMP appear increased. On the other hand, results yielded by our experiments allow us to estimate that environment preparing cGMP in the eye is the retina and the choroid."}
{"id": "PMID:220941", "title": "Oculodentodigital dysplasia. Four new reports and a literature review.", "content": "Four new patients with oculodentodigital dysplasia (ODD) have been examined. The salient and fairly constant features of ODD appear to be (1) unique facial appearance, (2) microcornea with other inconstant ocular findings, (3) syndactyly of the hands with additional characteristic phalangeal aberrations, (4) diffuse skeletal dysplasia, (5) enamel dysplasia, and (6) trichosis. Echographic studies indicate that ODD globes have microcornea with otherwise normal dimensions. An increased number of vessels crossing the optic discs was observed in three patients from one family. The distance between the inner canthi and the medial orbital walls in three patients we studied suggests that previous reports of hypertelorism may have been illusions resulting from microcornea, small palpebral fissures, and variably present epicanthus.", "contents": "Oculodentodigital dysplasia. Four new reports and a literature review. Four new patients with oculodentodigital dysplasia (ODD) have been examined. The salient and fairly constant features of ODD appear to be (1) unique facial appearance, (2) microcornea with other inconstant ocular findings, (3) syndactyly of the hands with additional characteristic phalangeal aberrations, (4) diffuse skeletal dysplasia, (5) enamel dysplasia, and (6) trichosis. Echographic studies indicate that ODD globes have microcornea with otherwise normal dimensions. An increased number of vessels crossing the optic discs was observed in three patients from one family. The distance between the inner canthi and the medial orbital walls in three patients we studied suggests that previous reports of hypertelorism may have been illusions resulting from microcornea, small palpebral fissures, and variably present epicanthus."}
{"id": "PMID:220942", "title": "Melanotic neuroectodermal tumor of infancy. An ophthalmic appearance.", "content": "Fullness developed in the left side of a 5-month-old male infant's face in the region of the zygoma. An incisional biopsy specimen showed the mass to be a melanotic neuroectodermal tumor, and radical excision was performed. There has been no recurrence of the tumor one year later. Tumors of this type occur in the face, particularly in the maxilla, and have only rarely been reported around the orbit.", "contents": "Melanotic neuroectodermal tumor of infancy. An ophthalmic appearance. Fullness developed in the left side of a 5-month-old male infant's face in the region of the zygoma. An incisional biopsy specimen showed the mass to be a melanotic neuroectodermal tumor, and radical excision was performed. There has been no recurrence of the tumor one year later. Tumors of this type occur in the face, particularly in the maxilla, and have only rarely been reported around the orbit."}
{"id": "PMID:220943", "title": "Herpetic whitlow and heratitis.", "content": "Two patients had herpes simplex infection of the fingertips (herpetic whitlow) associated with herpetic keratitis. Both patients were health-care professionals who probably acquired their disease from patients. Herpetic whitlow can be distinguished from a paronychia by the lack of a tense pulp space, formation of vesicles, and serous (rather than purulent) drainage. The fingertip inflammation resolves spontaneously, leaving normal healthy skin, in about two weeks.", "contents": "Herpetic whitlow and heratitis. Two patients had herpes simplex infection of the fingertips (herpetic whitlow) associated with herpetic keratitis. Both patients were health-care professionals who probably acquired their disease from patients. Herpetic whitlow can be distinguished from a paronychia by the lack of a tense pulp space, formation of vesicles, and serous (rather than purulent) drainage. The fingertip inflammation resolves spontaneously, leaving normal healthy skin, in about two weeks."}
{"id": "PMID:220944", "title": "Mucolipidosis IV. Histopathology of conjunctiva, cornea, and skin.", "content": "The condition of a 4-year-old white girl of Ashkenazi Jewish parents was diagnosed as mucolipidosis IV on the basis of marked corneal clouding and severe psychomotor retardation, in the absence of facial-skeletal dysplasia or abnormal mucopolysacchariduria. The results of histochemical and ultrastructural studies of conjunctiva, skin, and corneal epithelium confirmed the combined storage of acid mucopolysaccharide and complex lipid substances. An unusual histopathologic feature of mucolipidosis IV is the predisposition of extreme storage involvement of corneal epithelial cells with relative sparing of the keratocytes, which is a finding of potential therapeutic implication. In addition, application of electron microscopic study of cultured amniotic cells and conjunctival biopsy specimens to assess for the parents the mother's subsequent pregnancy additional emphasizes the value of ultrastructural studies in the diagnosis of lysosomal storage disease.", "contents": "Mucolipidosis IV. Histopathology of conjunctiva, cornea, and skin. The condition of a 4-year-old white girl of Ashkenazi Jewish parents was diagnosed as mucolipidosis IV on the basis of marked corneal clouding and severe psychomotor retardation, in the absence of facial-skeletal dysplasia or abnormal mucopolysacchariduria. The results of histochemical and ultrastructural studies of conjunctiva, skin, and corneal epithelium confirmed the combined storage of acid mucopolysaccharide and complex lipid substances. An unusual histopathologic feature of mucolipidosis IV is the predisposition of extreme storage involvement of corneal epithelial cells with relative sparing of the keratocytes, which is a finding of potential therapeutic implication. In addition, application of electron microscopic study of cultured amniotic cells and conjunctival biopsy specimens to assess for the parents the mother's subsequent pregnancy additional emphasizes the value of ultrastructural studies in the diagnosis of lysosomal storage disease."}
{"id": "PMID:220945", "title": "Cryosurgical treatment of glomus juglare tumor.", "content": "A 35 year-old Japanese female complained of a right-sided pulsation tinnitis, hearing disturbance, and facial weakness. Extensive radiographic studies including angiograms and retrograde juglar venography provided a diagnosis and localization of a tumor. Radical mastoidectomy was performed and a red grape-like glomus juglare tumor along the facial nerve was extirpated as there was a profuse hemorrhage from the tumor mass. Cryosurgery was then performed. Complete surgical removal is possible when the tumor is small, however, when the tumor involves the middle ear and mastoid area, complete extirpation cannot always be done. Radical mastoidectomy plus cryosurgery appears to be the most feasible management in the surgical treatment of glomus juglare tumor.", "contents": "Cryosurgical treatment of glomus juglare tumor. A 35 year-old Japanese female complained of a right-sided pulsation tinnitis, hearing disturbance, and facial weakness. Extensive radiographic studies including angiograms and retrograde juglar venography provided a diagnosis and localization of a tumor. Radical mastoidectomy was performed and a red grape-like glomus juglare tumor along the facial nerve was extirpated as there was a profuse hemorrhage from the tumor mass. Cryosurgery was then performed. Complete surgical removal is possible when the tumor is small, however, when the tumor involves the middle ear and mastoid area, complete extirpation cannot always be done. Radical mastoidectomy plus cryosurgery appears to be the most feasible management in the surgical treatment of glomus juglare tumor."}
{"id": "PMID:220947", "title": "[A case of multiple chemodectoma: clinical and electron microscopical studies].", "content": "We observed electronmicroscopically and clinically a case of multiple chemodectoma, which has occurred from glomus caroticum sinistra and glomus jugularis sinistra of a 18 year old boy. The diagnosis was especially made by an angiography of the left common carotid artery and by a retrograde venography of the left internal jugular vein. Electronmicroscopically two kinds of tumor cells in this chemodectoma were identified. These cytoplasmas showed cored neurosecretory granules measured 125 to 250 A in diameter markedly increasing in number. Moreover in the island of the tumor cells of the carotid body tumor we happened to observe the nerve ending.", "contents": "[A case of multiple chemodectoma: clinical and electron microscopical studies]. We observed electronmicroscopically and clinically a case of multiple chemodectoma, which has occurred from glomus caroticum sinistra and glomus jugularis sinistra of a 18 year old boy. The diagnosis was especially made by an angiography of the left common carotid artery and by a retrograde venography of the left internal jugular vein. Electronmicroscopically two kinds of tumor cells in this chemodectoma were identified. These cytoplasmas showed cored neurosecretory granules measured 125 to 250 A in diameter markedly increasing in number. Moreover in the island of the tumor cells of the carotid body tumor we happened to observe the nerve ending."}
{"id": "PMID:220950", "title": "A comparative study of the age-related patterns of decay of some nucleoside monophosphate kinases in human red cells.", "content": "The nucleoside monophosphate kinases, adenylate kinase (AK), guanylate kinase (GUK), and uridine monophosphate kinase (UMPK), were studied electrophoretically and quantitatively in density gradient fractions of human red cells from normal adults which contain red cells of differing mean age. The enzymes were found to differ both in their rates and patterns of decay and in secondary isozyme formation during the life of the red cell in the circulation. AK showed no appreciable enzyme decay and slight genetation of secondary isozymes; UMPK showed a rapid monophasic decline and no secondary isozyme formation; GUK showed intermediate overall loss of activity with a biphasic pattern of decay and marked secondary isozyme formation. A comparative study of the two common phenotypes of UMPK (UMPK 1 and UMPK 2-1) and of AK (AK 1 and AK 2-1) was made. The UMPK 2 isozyme showed a more rapid decay than the UMPK 1 isozyme, whereas no  difference was observed between the AK 1 and AK 2 isozymes.", "contents": "A comparative study of the age-related patterns of decay of some nucleoside monophosphate kinases in human red cells. The nucleoside monophosphate kinases, adenylate kinase (AK), guanylate kinase (GUK), and uridine monophosphate kinase (UMPK), were studied electrophoretically and quantitatively in density gradient fractions of human red cells from normal adults which contain red cells of differing mean age. The enzymes were found to differ both in their rates and patterns of decay and in secondary isozyme formation during the life of the red cell in the circulation. AK showed no appreciable enzyme decay and slight genetation of secondary isozymes; UMPK showed a rapid monophasic decline and no secondary isozyme formation; GUK showed intermediate overall loss of activity with a biphasic pattern of decay and marked secondary isozyme formation. A comparative study of the two common phenotypes of UMPK (UMPK 1 and UMPK 2-1) and of AK (AK 1 and AK 2-1) was made. The UMPK 2 isozyme showed a more rapid decay than the UMPK 1 isozyme, whereas no  difference was observed between the AK 1 and AK 2 isozymes."}
{"id": "PMID:220951", "title": "The amino acid sequence of cytochrome c' from the purple sulphur bacterium Chromatium vinosum.", "content": "An amino acid sequence is proposed for the cytochrome c' from the photosynthetic purple sulphur bacterium Chromatium vinosum strain D. It is single polypeptide chain of 131 residues, with haem-attachment cysteine residues at positions 121 and 124. The results discredit an earlier report [Dus, Bartsch & Kamen (1962) J. Biol. Chem 237, 3083--3093] of a di-haem peptide sequence from this protein. The sequence belongs to the same class as the published Alcaligenes and Rhodospirillum rubrum cytochrome c' squences, but the resemblance is not close. Detailed evidence for the amino acid sequence of the protein has been deposited as Supplementary Publication SUP 50,093 (15 pp.) 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. (1978) 169, 5.", "contents": "The amino acid sequence of cytochrome c' from the purple sulphur bacterium Chromatium vinosum. An amino acid sequence is proposed for the cytochrome c' from the photosynthetic purple sulphur bacterium Chromatium vinosum strain D. It is single polypeptide chain of 131 residues, with haem-attachment cysteine residues at positions 121 and 124. The results discredit an earlier report [Dus, Bartsch & Kamen (1962) J. Biol. Chem 237, 3083--3093] of a di-haem peptide sequence from this protein. The sequence belongs to the same class as the published Alcaligenes and Rhodospirillum rubrum cytochrome c' squences, but the resemblance is not close. Detailed evidence for the amino acid sequence of the protein has been deposited as Supplementary Publication SUP 50,093 (15 pp.) 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. (1978) 169, 5."}
{"id": "PMID:220952", "title": "A steady-state-kinetic model for formaldehyde dehydrogenase from human liver. A mechanism involving NAD+ and the hemimercaptal adduct of glutathione and formaldehyde as substrates and free glutathione as an allosteric activator of the enzyme.", "content": "The steady-state kinetics of formaldehyde dehydrogenase from human liver have been explored. Non-linearities were obtained in v-versus-v[S] plots. It was necessary and sufficient to consider two reactants of the equilibrium mixture of formaldehyde, glutathione and their hemimercaptal adduct for a complete description of the kinetics. A random sequential reaction scheme is proposed in which adduct and beta-NAD+ are the substrates. In addition, glutathione can bind to an allosteric regulatory site and only the glutathione-containing enzyme is considered productive. Various alternative reaction models were examined but no simple alterative was superior to the model chosen. The discrimination was largely based on results of non-linear regression analysis. Several S-substituted glutathione derivatives were tested as activators or inhibitors of the enzyme, but all were without effect. Thio-NAD+, nicotinamide--hypoxanthine dinucleotide and 3-acetylpyridine-adenine dinucleotide could substitute for beta-NAD+ as the nucleotide substrate. alpha-NAD+ and ADP-ribose were competitive inhibitors with respect to beta-NAD+ and non-competitive with glutathione and the adduct. When used simultaneously, the inhibitors were linear competitive versus each other, indicating a single nucleotide-binding site or, if more than one, non-co-operative binding sites.", "contents": "A steady-state-kinetic model for formaldehyde dehydrogenase from human liver. A mechanism involving NAD+ and the hemimercaptal adduct of glutathione and formaldehyde as substrates and free glutathione as an allosteric activator of the enzyme. The steady-state kinetics of formaldehyde dehydrogenase from human liver have been explored. Non-linearities were obtained in v-versus-v[S] plots. It was necessary and sufficient to consider two reactants of the equilibrium mixture of formaldehyde, glutathione and their hemimercaptal adduct for a complete description of the kinetics. A random sequential reaction scheme is proposed in which adduct and beta-NAD+ are the substrates. In addition, glutathione can bind to an allosteric regulatory site and only the glutathione-containing enzyme is considered productive. Various alternative reaction models were examined but no simple alterative was superior to the model chosen. The discrimination was largely based on results of non-linear regression analysis. Several S-substituted glutathione derivatives were tested as activators or inhibitors of the enzyme, but all were without effect. Thio-NAD+, nicotinamide--hypoxanthine dinucleotide and 3-acetylpyridine-adenine dinucleotide could substitute for beta-NAD+ as the nucleotide substrate. alpha-NAD+ and ADP-ribose were competitive inhibitors with respect to beta-NAD+ and non-competitive with glutathione and the adduct. When used simultaneously, the inhibitors were linear competitive versus each other, indicating a single nucleotide-binding site or, if more than one, non-co-operative binding sites."}
{"id": "PMID:220953", "title": "Characterization of the second prosthetic group of the flavoenzyme NADH-acceptor reductase (component C) of the methane mono-oxygenase from Methylococcus capsulatus (Bath).", "content": "1. A new two-step purification is described that routinely yields 100mg quantities of component C for biochemical studies. 2. Chemical analyses show component C purified by this procedure to contain 2 g-atoms of iron, 2 mol of acid-labile sulphide (S) and 1 mol of FAD per mol of protein. 3. The Fe-S core of component C was extruded by treating the protein with p-methoxybenzenethiol in hexamethyl phosphoramide/50mM-Tris/HCl buffer, pH 8.5 (4:1, v/v), under anaerobic conditions. The spectral properties of the extruded core suggest that component C contains 1 mol of [2Fe-2S(S-Cys)4] centre per mol of protein. 4. E.p.r. spectroscopy confirms the presence of a Fe-S centre in component C. 5. Component C catalyses the reduction by NADH of ferricyanide, 2,6-dichlorophenol-indophenol or horse heart cytochrome c, with specific activities of 50--230 units/mg of protein. 6. The optimum pH for the NADH-acceptor reductase activity is 8.5--9.0, and the apparent Km values for NADH and NADPH are 0.05mM and 15.5mM respectively. 7. Unlike methane mono-oxygenase activity, NADH-acceptor reductase activity of component C is not inhibited by 8-hydroxyquinoline or by acetylene.", "contents": "Characterization of the second prosthetic group of the flavoenzyme NADH-acceptor reductase (component C) of the methane mono-oxygenase from Methylococcus capsulatus (Bath). 1. A new two-step purification is described that routinely yields 100mg quantities of component C for biochemical studies. 2. Chemical analyses show component C purified by this procedure to contain 2 g-atoms of iron, 2 mol of acid-labile sulphide (S) and 1 mol of FAD per mol of protein. 3. The Fe-S core of component C was extruded by treating the protein with p-methoxybenzenethiol in hexamethyl phosphoramide/50mM-Tris/HCl buffer, pH 8.5 (4:1, v/v), under anaerobic conditions. The spectral properties of the extruded core suggest that component C contains 1 mol of [2Fe-2S(S-Cys)4] centre per mol of protein. 4. E.p.r. spectroscopy confirms the presence of a Fe-S centre in component C. 5. Component C catalyses the reduction by NADH of ferricyanide, 2,6-dichlorophenol-indophenol or horse heart cytochrome c, with specific activities of 50--230 units/mg of protein. 6. The optimum pH for the NADH-acceptor reductase activity is 8.5--9.0, and the apparent Km values for NADH and NADPH are 0.05mM and 15.5mM respectively. 7. Unlike methane mono-oxygenase activity, NADH-acceptor reductase activity of component C is not inhibited by 8-hydroxyquinoline or by acetylene."}
{"id": "PMID:220954", "title": "Analysis of histones from the yeast Saccharomyces carlsbergensis.", "content": "Basic chromosomal proteins were isolated from the chromatin of the yeast Saccharomyces carlsbergensis by extraction with H2SO4 and were purified by ion-exchange chromatography. Electrophoresis of the purified fraction on acetic acid/urea gels revealed the presence of four main components. These four proteins were identified as histones H2A, H2B, H3 and H4 on the basis of their amino acid composition, molecular weight and solubility properties, all of which are very similar to the corresponding properties of the various histone proteins from other eukaryotic organisms. A fifth basic protein could be isolated from yeast chromatin by extraction with HClO4. The available evidence indicates this protein to be an H1-type histone. Yeast thus appears to contain a complete set of histone proteins which are strongly homologous to the histones occurring in higher eukaryotes.", "contents": "Analysis of histones from the yeast Saccharomyces carlsbergensis. Basic chromosomal proteins were isolated from the chromatin of the yeast Saccharomyces carlsbergensis by extraction with H2SO4 and were purified by ion-exchange chromatography. Electrophoresis of the purified fraction on acetic acid/urea gels revealed the presence of four main components. These four proteins were identified as histones H2A, H2B, H3 and H4 on the basis of their amino acid composition, molecular weight and solubility properties, all of which are very similar to the corresponding properties of the various histone proteins from other eukaryotic organisms. A fifth basic protein could be isolated from yeast chromatin by extraction with HClO4. The available evidence indicates this protein to be an H1-type histone. Yeast thus appears to contain a complete set of histone proteins which are strongly homologous to the histones occurring in higher eukaryotes."}
{"id": "PMID:220955", "title": "Nucleotide metabolism by microsomal UDP-glucuronyltransferase and nucleoside diphosphatase as determine by 31P nuclear-magnetic-resonance spectroscopy.", "content": "31P n.m.r. spectroscopy was used to study the nucleotide kinetics of UDP-glucuronyltransferase and associated reactions in the liver microsomal fraction. The effects of Mg2+ and EDTA on these reactions were investigated qualitatively. It was found that the rabbit microsomal fraction has no nucleoside pyrophosphatase activity, that UDP was immediately hydrolysed and that it was released from the microsomal surface. Reverse glucuronyltransferase could be demonstrated. The results are discussed with reference to functional coupling of UDP-glucuronyltransferase to other enzymes and the effects of Mg2+ and EDTA on the system.", "contents": "Nucleotide metabolism by microsomal UDP-glucuronyltransferase and nucleoside diphosphatase as determine by 31P nuclear-magnetic-resonance spectroscopy. 31P n.m.r. spectroscopy was used to study the nucleotide kinetics of UDP-glucuronyltransferase and associated reactions in the liver microsomal fraction. The effects of Mg2+ and EDTA on these reactions were investigated qualitatively. It was found that the rabbit microsomal fraction has no nucleoside pyrophosphatase activity, that UDP was immediately hydrolysed and that it was released from the microsomal surface. Reverse glucuronyltransferase could be demonstrated. The results are discussed with reference to functional coupling of UDP-glucuronyltransferase to other enzymes and the effects of Mg2+ and EDTA on the system."}
{"id": "PMID:220956", "title": "Compound C2, a product of the reaction of oxygen and the mixed-valence state of cytochrome oxidase. Optical evidence for a type-I copper.", "content": "Compound C2 is a product of the reaction of O2 and the mixed-valence state of cytochrome oxidase. The mixed-valence state of membrane-bound cytochrome oxidase is obtained at -24 degrees C, by using either ferricyanide or yeast peroxidase complex ES as oxidants, and the configurations of oxidized haem a and its associated copper (a3+Cua2+) and of reduced haem a3 and its associated copper (ac3+.CO.Cua3+) are obtained. The mixed-valence-state cytochrome oxidase mixed with O2 at -24 degrees C and flash-photolysed at -60 to -100 degrees C reacts with O2 and initially forms an oxy compound (A2) similar to that formed from the fully reduced state (A1). Thereafter the course of the reaction differs from that obtained in the fully reduced state, and absorbance increases are observed at 740--750 nm and 609 nm and a decrease at 444 nm, with no increase in absorbance at 655 nm. One possible attribution of the absorbance increases is to charge-transfer interaction between the iron of haem a3 and the copper associated with haem a3, Cua3(2+), having properties of a type-I 'blue' copper. A possible attribution of the decrease in absorbance at 444 nm is to liganding of a3(2+). A related explanation is that the 609 nm absorbance involves a charge-transfer interaction of both iron and copper as a mixed-valence binuclear complex, Cua3, having properties of a non-blue copper. Intermediates in addition to Compound C2 are not yet identifiable by chemical or spectroscopic tests. The kinetic and equilibrium properties of Compound C2 are described.", "contents": "Compound C2, a product of the reaction of oxygen and the mixed-valence state of cytochrome oxidase. Optical evidence for a type-I copper. Compound C2 is a product of the reaction of O2 and the mixed-valence state of cytochrome oxidase. The mixed-valence state of membrane-bound cytochrome oxidase is obtained at -24 degrees C, by using either ferricyanide or yeast peroxidase complex ES as oxidants, and the configurations of oxidized haem a and its associated copper (a3+Cua2+) and of reduced haem a3 and its associated copper (ac3+.CO.Cua3+) are obtained. The mixed-valence-state cytochrome oxidase mixed with O2 at -24 degrees C and flash-photolysed at -60 to -100 degrees C reacts with O2 and initially forms an oxy compound (A2) similar to that formed from the fully reduced state (A1). Thereafter the course of the reaction differs from that obtained in the fully reduced state, and absorbance increases are observed at 740--750 nm and 609 nm and a decrease at 444 nm, with no increase in absorbance at 655 nm. One possible attribution of the absorbance increases is to charge-transfer interaction between the iron of haem a3 and the copper associated with haem a3, Cua3(2+), having properties of a type-I 'blue' copper. A possible attribution of the decrease in absorbance at 444 nm is to liganding of a3(2+). A related explanation is that the 609 nm absorbance involves a charge-transfer interaction of both iron and copper as a mixed-valence binuclear complex, Cua3, having properties of a non-blue copper. Intermediates in addition to Compound C2 are not yet identifiable by chemical or spectroscopic tests. The kinetic and equilibrium properties of Compound C2 are described."}
{"id": "PMID:220957", "title": "The mechanism of adduct formation between NAD+ and pyruvate bound to pig heart lactate dehydrogenase.", "content": "1. The rate of adduct formation between NAD+ and enol-pyruvate at the active site of lactate dehydrogenase is determined by the rate of enolization of pyruvate in solution. 2. The proportion of enol-pyruvate solutions is less than 0.01%. 3. The overall dissociation constant of adduct formation is less than 5 X 10(-8) M for pig heart lactate dehydrogenase at pH 7.0. 4. The unusual kinetics for adduct formation previously observed in the case of rabbit muscle lactate dehydrogenase [Griffin & Criddle (1970) Biochemistry 9, 1195--1205] may be attributed to the concentration of enol-pyruvate in solution being considerably less than the concentration of enzyme.", "contents": "The mechanism of adduct formation between NAD+ and pyruvate bound to pig heart lactate dehydrogenase. 1. The rate of adduct formation between NAD+ and enol-pyruvate at the active site of lactate dehydrogenase is determined by the rate of enolization of pyruvate in solution. 2. The proportion of enol-pyruvate solutions is less than 0.01%. 3. The overall dissociation constant of adduct formation is less than 5 X 10(-8) M for pig heart lactate dehydrogenase at pH 7.0. 4. The unusual kinetics for adduct formation previously observed in the case of rabbit muscle lactate dehydrogenase [Griffin & Criddle (1970) Biochemistry 9, 1195--1205] may be attributed to the concentration of enol-pyruvate in solution being considerably less than the concentration of enzyme."}
{"id": "PMID:220958", "title": "Structure and metabolism of sulphated glycosaminoglycans in cultures of human fibroblasts. Structural characteristics of co-polymeric galactosaminoglycans in sequential extracts of fibroblasts during pulse-chase experiments.", "content": "1. Human embryonic lung and skin fibroblasts were allowed to incorporate 32SO42- or 35SO42- and D-[1-3H]glucosamine. After removal of the medium the monolayer was subjected to sequential extractions by using EDTA, brief trypsin digestion, extraction with dithiothreitol ofllowed by freeze--thawing and extraction with trichloroacetic acid. The heparan sulphate and galactosaminoglycan contents of the various extracts were estimated after deaminative cleavage of the former component. Heparan sulphate was the major component of the trypsin digest, whereas galactosaminoglycans were the dominant component of other fractions. 2. Galactosaminoglycans of the various fractions were subjected to chemical (periodate oxidation/alkaline elimination) and enzymic (chondroitinase-AC and -ABC, as well as testicular hyaluronidase) degradations. Galactosaminoglycans from the insoluble cell fraction and the dithiothreitol extract contained larger amounts of L-iduronic acid than did those of other fractions. 3. Pulse-chase experiments were performed with and without replating of the cells at the start of the chase period. Radioactive glycans were isolated from the various extracts during the chase period. The half-lives of glycans of the insoluble cell fraction and the dithioreitol extract were shorter (5--8h) than were those of the trypsin digest and the EDTA extract (22h and 11h respectively). After replating of the cells in chase medium, radioactive cell-associated glycans were secreted from the cells and could be recovered in the trypsin digest, the EDTA extract and the medium. Furthermore, 35S/3H ratios of glycans from all these fractions decreased during the chase period. The following conclusions were reached. The insoluble cell fraction contains the synthesis pool and some structural material, whereas the soluble cell fraction is the storage and degradation pool. The dithiothreitol extract appears to contain the immediate precursors of secreted material. The trypsin-released glycans comprise structural components as well as material destined for pinocytosis or secretion into the medium. The EDTA extract is considered to consist of glycans en route to the medium. 4. The two presumptive precursor pools were preferentially depleted of L-iduronic acid-rich galactosaminoglycans during the chase. Glycans recovered from the trypsin digest, the EDTA extract and the medium during the chase contained larger amounts of periodate-resistant uronic acid residues (D-glucuronic acid and/or L-iduronic acid O-sulphate) than did their precursors. It is proposed that polymer-level modifications of secreted glycans are partly responsible for the results.", "contents": "Structure and metabolism of sulphated glycosaminoglycans in cultures of human fibroblasts. Structural characteristics of co-polymeric galactosaminoglycans in sequential extracts of fibroblasts during pulse-chase experiments. 1. Human embryonic lung and skin fibroblasts were allowed to incorporate 32SO42- or 35SO42- and D-[1-3H]glucosamine. After removal of the medium the monolayer was subjected to sequential extractions by using EDTA, brief trypsin digestion, extraction with dithiothreitol ofllowed by freeze--thawing and extraction with trichloroacetic acid. The heparan sulphate and galactosaminoglycan contents of the various extracts were estimated after deaminative cleavage of the former component. Heparan sulphate was the major component of the trypsin digest, whereas galactosaminoglycans were the dominant component of other fractions. 2. Galactosaminoglycans of the various fractions were subjected to chemical (periodate oxidation/alkaline elimination) and enzymic (chondroitinase-AC and -ABC, as well as testicular hyaluronidase) degradations. Galactosaminoglycans from the insoluble cell fraction and the dithiothreitol extract contained larger amounts of L-iduronic acid than did those of other fractions. 3. Pulse-chase experiments were performed with and without replating of the cells at the start of the chase period. Radioactive glycans were isolated from the various extracts during the chase period. The half-lives of glycans of the insoluble cell fraction and the dithioreitol extract were shorter (5--8h) than were those of the trypsin digest and the EDTA extract (22h and 11h respectively). After replating of the cells in chase medium, radioactive cell-associated glycans were secreted from the cells and could be recovered in the trypsin digest, the EDTA extract and the medium. Furthermore, 35S/3H ratios of glycans from all these fractions decreased during the chase period. The following conclusions were reached. The insoluble cell fraction contains the synthesis pool and some structural material, whereas the soluble cell fraction is the storage and degradation pool. The dithiothreitol extract appears to contain the immediate precursors of secreted material. The trypsin-released glycans comprise structural components as well as material destined for pinocytosis or secretion into the medium. The EDTA extract is considered to consist of glycans en route to the medium. 4. The two presumptive precursor pools were preferentially depleted of L-iduronic acid-rich galactosaminoglycans during the chase. Glycans recovered from the trypsin digest, the EDTA extract and the medium during the chase contained larger amounts of periodate-resistant uronic acid residues (D-glucuronic acid and/or L-iduronic acid O-sulphate) than did their precursors. It is proposed that polymer-level modifications of secreted glycans are partly responsible for the results."}
{"id": "PMID:220959", "title": "Turnover of prolyl hydroxylase tetramers and the monomer-size protein in chick-embryo cartilaginous bone and lung in vivo.", "content": "The turnover of prolyl hydroxylase and an immunoreactive protein that corresponds in size to the smaller subunit of the enzyme was studied in vivo after injection of [(3)H]leucine into 11-day chick embryos. The specific radioactivity and total radioactivity of the monomer-size protein were much higher than those of the enzyme tetramers in the cartilaginous bone at 3h and 12h after the radioisotope injection, indicating that the monomer-size protein represents precursors rather than degradation products of the enzyme tetramers. Between 24 and 144h after the injection the specific radioactivity and total radioactivity of the two forms of the enzyme protein showed essentially identical decay rates, the observed specific radioactivity of the monomer-size protein being about 120-130% and total radioactivity about 80% of that of the enzyme tetramers. The true half-life, when corrected for dilution caused by tissue growth and re-utilization of the [(3)H]leucine, was 37.9h for the monomer-size protein and 39.0h for the tetramers. The results obtained in the lung were less reliable owing to high blank radioactivity values in the immunoprecipitation, but even so some definite differences were found between this tissue and the cartilaginous bone. The specific radioactivity of both forms of the enzyme protein at 24h was only about 20-25% of that in the cartilaginous bone. The total radioactivity of the monomer-size protein in the lung remained about 5 times that of the enzyme tetramers, whereas it was only about 0.8 times that of the tetramers in the cartilaginous bone. As in the cartilaginous bone, the decay rates of both forms of the enzyme protein were essentially identical in the lung, with a true half-life of about 46h. The results suggest that the rate of prolyl hydroxylase synthesis is slower in the lung than in the cartilaginous bone, whereas the degradation rates are fairly similar in these two tissues. The data further suggest that, in the lung at least, a large part of the monomer-size protein became degraded without being converted into enzyme tetramers.", "contents": "Turnover of prolyl hydroxylase tetramers and the monomer-size protein in chick-embryo cartilaginous bone and lung in vivo. The turnover of prolyl hydroxylase and an immunoreactive protein that corresponds in size to the smaller subunit of the enzyme was studied in vivo after injection of [(3)H]leucine into 11-day chick embryos. The specific radioactivity and total radioactivity of the monomer-size protein were much higher than those of the enzyme tetramers in the cartilaginous bone at 3h and 12h after the radioisotope injection, indicating that the monomer-size protein represents precursors rather than degradation products of the enzyme tetramers. Between 24 and 144h after the injection the specific radioactivity and total radioactivity of the two forms of the enzyme protein showed essentially identical decay rates, the observed specific radioactivity of the monomer-size protein being about 120-130% and total radioactivity about 80% of that of the enzyme tetramers. The true half-life, when corrected for dilution caused by tissue growth and re-utilization of the [(3)H]leucine, was 37.9h for the monomer-size protein and 39.0h for the tetramers. The results obtained in the lung were less reliable owing to high blank radioactivity values in the immunoprecipitation, but even so some definite differences were found between this tissue and the cartilaginous bone. The specific radioactivity of both forms of the enzyme protein at 24h was only about 20-25% of that in the cartilaginous bone. The total radioactivity of the monomer-size protein in the lung remained about 5 times that of the enzyme tetramers, whereas it was only about 0.8 times that of the tetramers in the cartilaginous bone. As in the cartilaginous bone, the decay rates of both forms of the enzyme protein were essentially identical in the lung, with a true half-life of about 46h. The results suggest that the rate of prolyl hydroxylase synthesis is slower in the lung than in the cartilaginous bone, whereas the degradation rates are fairly similar in these two tissues. The data further suggest that, in the lung at least, a large part of the monomer-size protein became degraded without being converted into enzyme tetramers."}
{"id": "PMID:220960", "title": "The microbial metabolism of C1 compounds. Oxidative phosphorylation in membrane preparations of Pseudomonas AM1.", "content": "A method is described for preparation of membrane vesicles (diameter 80nm) capable of respiration-linked ATP synthesis. Vesicles prepared from succinate-grown bacteria oxidized NADH, succinate and ascorbate plus NNN'N'-tetramethylphenylenediamine; vesicles prepared from methanol-grown bacteria also oxidized methanol and formaldehyde, but they were otherwise identical. The uncoupling agent carbonyl cyanide chlorophenylhydrazone and the adenosine triphosphatase inhibitor dicyclohexylcarbodi-imide both inhibited ATP synthesis, whereas they had no effect on the rate of respiration. Rotenone inhibited ATP synthesis and respiration with NADH as substrate; antimycin A inhibited with succinate as substrate, and cyanide inhibited with all substrates. P/O ratios were usually 0.7-1.3 with NADH, 0.6-1.0 with succinate and 0.2-0.6 with reduced NNN'N'-tetramethylphenylenediamine or methanol as respiratory substrate. When 2,6-dichlorophenol-indophenol was used as an alternative electron acceptor to O(2) (NADH as donor) the P/2e ratio was 1.65. Although these P/O ratios are minimum values, because they do not take into account unknown amounts of uncoupled O(2) consumption, they are consistent with previous proposals [O'Keeffe & Anthony (1978) Biochem, J.170, 561-567] based on measurements of proton translocation in whole cells. The results also confirm that methanol dehydrogenase and cytochromes c and a/a(3) are arranged so that the first step in methanol oxidation is coupled to synthesis of ATP.", "contents": "The microbial metabolism of C1 compounds. Oxidative phosphorylation in membrane preparations of Pseudomonas AM1. A method is described for preparation of membrane vesicles (diameter 80nm) capable of respiration-linked ATP synthesis. Vesicles prepared from succinate-grown bacteria oxidized NADH, succinate and ascorbate plus NNN'N'-tetramethylphenylenediamine; vesicles prepared from methanol-grown bacteria also oxidized methanol and formaldehyde, but they were otherwise identical. The uncoupling agent carbonyl cyanide chlorophenylhydrazone and the adenosine triphosphatase inhibitor dicyclohexylcarbodi-imide both inhibited ATP synthesis, whereas they had no effect on the rate of respiration. Rotenone inhibited ATP synthesis and respiration with NADH as substrate; antimycin A inhibited with succinate as substrate, and cyanide inhibited with all substrates. P/O ratios were usually 0.7-1.3 with NADH, 0.6-1.0 with succinate and 0.2-0.6 with reduced NNN'N'-tetramethylphenylenediamine or methanol as respiratory substrate. When 2,6-dichlorophenol-indophenol was used as an alternative electron acceptor to O(2) (NADH as donor) the P/2e ratio was 1.65. Although these P/O ratios are minimum values, because they do not take into account unknown amounts of uncoupled O(2) consumption, they are consistent with previous proposals [O'Keeffe & Anthony (1978) Biochem, J.170, 561-567] based on measurements of proton translocation in whole cells. The results also confirm that methanol dehydrogenase and cytochromes c and a/a(3) are arranged so that the first step in methanol oxidation is coupled to synthesis of ATP."}
{"id": "PMID:220961", "title": "The permeability of rat liver lysosomes to sugars. Evidence for carrier-mediated facilitated diffusion.", "content": "1. By the osmotic-protection method, the penetration of sugars through the rat liver lysosomal membranes was studied with a view of determining whether sugar uptake was by facilitated diffusion. 2. The following criteria for this type of transport were established: sugar specificity, the order of uptake being 2-deoxy-D-glucose less than D-glucose less than D-mannose less than D-galactose less than D-ribose less than 2-deoxy-D-ribose; stereospecificity, the uptake of L-glucose and L-ribose being 50% slower than their D-stereoisomers; inhibition by 1 MM-phlorrhizin and 1 M-cytochalastin B; competition between sugars for uptake, and a Q10 (rate difference over a 10 degrees C temperature range) for uptake of approx. 2.8. 3. It is proposed that sugar uptake into lysosomes from rat liver is by facilitated diffusion.", "contents": "The permeability of rat liver lysosomes to sugars. Evidence for carrier-mediated facilitated diffusion. 1. By the osmotic-protection method, the penetration of sugars through the rat liver lysosomal membranes was studied with a view of determining whether sugar uptake was by facilitated diffusion. 2. The following criteria for this type of transport were established: sugar specificity, the order of uptake being 2-deoxy-D-glucose less than D-glucose less than D-mannose less than D-galactose less than D-ribose less than 2-deoxy-D-ribose; stereospecificity, the uptake of L-glucose and L-ribose being 50% slower than their D-stereoisomers; inhibition by 1 MM-phlorrhizin and 1 M-cytochalastin B; competition between sugars for uptake, and a Q10 (rate difference over a 10 degrees C temperature range) for uptake of approx. 2.8. 3. It is proposed that sugar uptake into lysosomes from rat liver is by facilitated diffusion."}
{"id": "PMID:220962", "title": "Interaction between insulin-storage granules and F-actin in vitro.", "content": "Possible interactions between polymerized (F-) actin and insulin-storage granules from rat islets of Langerhans were examined in vitro by comparing the sedimentation of the granules in the presence of various actin concentrations. Actin in the concentration range 0.1--0.5 mg/ml produced a retardation in granule-sedimentation rates consistent with binding of the granules to the actin filaments. The interaction was increased by addition of ATP (2mM), but was decreased by CaCl2 (0.1 mM). Binding of granules to actin was unaffected by cyclic AMP or by preincubation of the granules with phospholipase C. Specificity of the interaction was confirmed by the use of depolymerized (G-) actin and of myosin to provide a solution of comparable viscosity; neither of these caused any alteration of granule sedimentation. Possible implications of this interaction of insulin-storage granules with actin for the mechanism of insulin secretion are briefly discussed.", "contents": "Interaction between insulin-storage granules and F-actin in vitro. Possible interactions between polymerized (F-) actin and insulin-storage granules from rat islets of Langerhans were examined in vitro by comparing the sedimentation of the granules in the presence of various actin concentrations. Actin in the concentration range 0.1--0.5 mg/ml produced a retardation in granule-sedimentation rates consistent with binding of the granules to the actin filaments. The interaction was increased by addition of ATP (2mM), but was decreased by CaCl2 (0.1 mM). Binding of granules to actin was unaffected by cyclic AMP or by preincubation of the granules with phospholipase C. Specificity of the interaction was confirmed by the use of depolymerized (G-) actin and of myosin to provide a solution of comparable viscosity; neither of these caused any alteration of granule sedimentation. Possible implications of this interaction of insulin-storage granules with actin for the mechanism of insulin secretion are briefly discussed."}
{"id": "PMID:220963", "title": "Stimulation of glucose transport in rat adipocytes by insulin, adenosine, nicotinic acid and hydrogen peroxide. Role of adenosine 3':5'-cyclic monophosphate.", "content": "Glucose transport into adipocytes of the rat was measured by monitoring the conversion of [1-(14)C]glucose into (14)CO(2). Glucose transport was made rate-limiting by increasing the flux through the pentose phosphate pathway with phenazine methosulphate, an agent that rapidly reoxidizes NADPH. Under these conditions, the observed rate of glucose disappearance from the incubation medium was about 20% higher than the rate of conversion of the C-1 of glucose into (14)CO(2). Apparent rates of glucose transport were significantly increased by insulin, H(2)O(2), adenosine and nicotinic acid. Stimulation of the apparent rate of glucose transport by insulin was dependent on adipocyte concentration, the hormone being most effective at relatively high cell concentrations. Adenosine and nicotinic acid further enhanced the maximum stimulation of glucose transport by insulin. Potentiation of insulin action by adenosine was more pronounced at lower cell concentrations. At relatively high cell concentrations the stimulatory action of insulin was markedly decreased by adenosine deaminase. Stimulation of apparent rates of glucose transport by the compounds noted above were antagonized by agents that increased intracellular cyclic AMP concentrations (theophylline and isoprenaline) and by dibutyryl cyclic AMP. Intracellular concentrations of cyclic AMP were significantly lowered when adipocytes were incubated with insulin, H(2)O(2), adenosine or nicotinic acid. These effects were observed under basal conditions or when intracellular cyclic AMP concentrations were elevated by theophylline or isoprenaline. On the basis of the above data, we suggest that insulin, H(2)O(2), adenosine and nicotinic acid may all stimulate glucose transport in rat adipocytes by lowering the intracellular cyclic AMP concentration. These data therefore support the hypothesis that cyclic AMP inhibits glucose transport in rat adipocytes.", "contents": "Stimulation of glucose transport in rat adipocytes by insulin, adenosine, nicotinic acid and hydrogen peroxide. Role of adenosine 3':5'-cyclic monophosphate. Glucose transport into adipocytes of the rat was measured by monitoring the conversion of [1-(14)C]glucose into (14)CO(2). Glucose transport was made rate-limiting by increasing the flux through the pentose phosphate pathway with phenazine methosulphate, an agent that rapidly reoxidizes NADPH. Under these conditions, the observed rate of glucose disappearance from the incubation medium was about 20% higher than the rate of conversion of the C-1 of glucose into (14)CO(2). Apparent rates of glucose transport were significantly increased by insulin, H(2)O(2), adenosine and nicotinic acid. Stimulation of the apparent rate of glucose transport by insulin was dependent on adipocyte concentration, the hormone being most effective at relatively high cell concentrations. Adenosine and nicotinic acid further enhanced the maximum stimulation of glucose transport by insulin. Potentiation of insulin action by adenosine was more pronounced at lower cell concentrations. At relatively high cell concentrations the stimulatory action of insulin was markedly decreased by adenosine deaminase. Stimulation of apparent rates of glucose transport by the compounds noted above were antagonized by agents that increased intracellular cyclic AMP concentrations (theophylline and isoprenaline) and by dibutyryl cyclic AMP. Intracellular concentrations of cyclic AMP were significantly lowered when adipocytes were incubated with insulin, H(2)O(2), adenosine or nicotinic acid. These effects were observed under basal conditions or when intracellular cyclic AMP concentrations were elevated by theophylline or isoprenaline. On the basis of the above data, we suggest that insulin, H(2)O(2), adenosine and nicotinic acid may all stimulate glucose transport in rat adipocytes by lowering the intracellular cyclic AMP concentration. These data therefore support the hypothesis that cyclic AMP inhibits glucose transport in rat adipocytes."}
{"id": "PMID:220964", "title": "The effects of lipid phase transitions on the interaction of mitochondrial NADH--ubiquinone oxidoreductase with ubiquinol--cytochrome c oxidoreductase.", "content": "1. The endogenous phosphatidylcholine and phosphatidylethanolamine of Complexes I and III from bovine heart mitochondria may be completely replaced with 1,2-ditetradecanoyl-sn-glycero-3-phosphocholine with at least partial retention of activity. 2. The lipid-replaced enzymes associate in 1:1 molar ratio to give a Complex I--III unit catalysing NADH-cytochrome c oxidoreductase activity. 3. On increasing the concentration of ubiquinone-10 and the synthetic phospholipid, the lipid-replaced Complexes appear to operate independently of each other as in the natural membrane. Thus the lipid-replaced enzymes associate in exactly the same ways as the enzymes containing natural phospholipids. 4. Arrhenius plots of NADH--cytochrome c oxidoreductase activity reconstituted from lipid-replaced Complexes I and III exhibit changes in slope at 24 degrees C. When the concentrations of phospholipid and ubiquinone-10 are increased, the Arrhenius plots show discontinuities at 24 degrees C as well as changes in slope. 5. The kinetics of cytochrome b reduction by NADH were measured in mixtures containing 2 mol of Complex III/mol of Complex I. When the enzymes contained natural phospholipids. the reduction kinetics were biphasic. When the enzymes had been supplemented with further phospholipid and ubiquinone-10 the kinetics were monophasic. When lipid-replaced enzymes were supplemented with 1,2-ditetradecanoyl-sn-glycero-3-phosphocholine and ubiquinone-10, reduction of cytochrome b was monophasic above the phase-transition temperature of the lipid but biphasic below it. 6. These findings are interpreted in terms of the model for the interaction of Complexes in the natural membrane proposed by Heron, Ragan & Trum-power [(1978) Biochem. J. 174, 791--800].", "contents": "The effects of lipid phase transitions on the interaction of mitochondrial NADH--ubiquinone oxidoreductase with ubiquinol--cytochrome c oxidoreductase. 1. The endogenous phosphatidylcholine and phosphatidylethanolamine of Complexes I and III from bovine heart mitochondria may be completely replaced with 1,2-ditetradecanoyl-sn-glycero-3-phosphocholine with at least partial retention of activity. 2. The lipid-replaced enzymes associate in 1:1 molar ratio to give a Complex I--III unit catalysing NADH-cytochrome c oxidoreductase activity. 3. On increasing the concentration of ubiquinone-10 and the synthetic phospholipid, the lipid-replaced Complexes appear to operate independently of each other as in the natural membrane. Thus the lipid-replaced enzymes associate in exactly the same ways as the enzymes containing natural phospholipids. 4. Arrhenius plots of NADH--cytochrome c oxidoreductase activity reconstituted from lipid-replaced Complexes I and III exhibit changes in slope at 24 degrees C. When the concentrations of phospholipid and ubiquinone-10 are increased, the Arrhenius plots show discontinuities at 24 degrees C as well as changes in slope. 5. The kinetics of cytochrome b reduction by NADH were measured in mixtures containing 2 mol of Complex III/mol of Complex I. When the enzymes contained natural phospholipids. the reduction kinetics were biphasic. When the enzymes had been supplemented with further phospholipid and ubiquinone-10 the kinetics were monophasic. When lipid-replaced enzymes were supplemented with 1,2-ditetradecanoyl-sn-glycero-3-phosphocholine and ubiquinone-10, reduction of cytochrome b was monophasic above the phase-transition temperature of the lipid but biphasic below it. 6. These findings are interpreted in terms of the model for the interaction of Complexes in the natural membrane proposed by Heron, Ragan & Trum-power [(1978) Biochem. J. 174, 791--800]."}
{"id": "PMID:220965", "title": "Induction of N-acetylglucosamine-catabolic pathway in spheroplasts of Candida albicans.", "content": "Synthesis of N-acetylglucosamine-catabolic enzymes, namely permease (high-affinity uptake system), kinase and deaminase was studied in the spheroplasts of the yeast Candida albicans. The presence of N-acetylglucosamine as inducer is essential for the induced synthesis of these enzymes in the spheroplasts, which were active for at least 8--9 h. However, some of the newly synthesized kinase and deaminase leaked out from the spheroplasts into the medium during induction. Experiments with inhibitors of RNA and protein synthesis indicate that the appearance of new enzyme activities is dependent on concomitant new protein synthesis and the inducer operates at a transcriptional level. However, inhibitors of DNA synthesis, e.g. mitomycin-C and hydroxyurea, had no effect on the synthesis of these enzymes.", "contents": "Induction of N-acetylglucosamine-catabolic pathway in spheroplasts of Candida albicans. Synthesis of N-acetylglucosamine-catabolic enzymes, namely permease (high-affinity uptake system), kinase and deaminase was studied in the spheroplasts of the yeast Candida albicans. The presence of N-acetylglucosamine as inducer is essential for the induced synthesis of these enzymes in the spheroplasts, which were active for at least 8--9 h. However, some of the newly synthesized kinase and deaminase leaked out from the spheroplasts into the medium during induction. Experiments with inhibitors of RNA and protein synthesis indicate that the appearance of new enzyme activities is dependent on concomitant new protein synthesis and the inducer operates at a transcriptional level. However, inhibitors of DNA synthesis, e.g. mitomycin-C and hydroxyurea, had no effect on the synthesis of these enzymes."}
{"id": "PMID:220966", "title": "The metabolic conversion of very-low-density lipoprotein into low-density lipoprotein by the extrahepatic tissues of the rat.", "content": "1. The work reported was designed to provide quantitative information about the capacity of the extrahepatic tissues of the rat to degrade injected VLD lipoproteins (very-low-density lipoproteins, d less than 1.006) to LD lipoproteins (low-density lipoproteins, d 1.006--1.063) and to study the fate of the different VLD-lipoprotein apoproteins during the degradative process. 2. Rat liver VLD lipoproteins, radioactively labelled in their protein moieties, were produced by the perfusion of the organ and were either injected into the circulation of the supradiaphragmatic rats or incubated in rat plasma at 37 degrees C. At a time (75 min) when approx. 90% of the triacylglycerol of the VLD lipoproteins had been hydrolysed the supradiaphragmatic rats were bled and VLD lipoproteins, LD lipoproteins and HD lipoproteins (high-density lipoproteins, d 1.063--1.21) were separated from their plasma and from the plasma incubated in vitro. The apoproteins of each of the lipoprotein classes were resolved by gel-filtration chromatography into three main fractions, designated peaks I, II and III. 3. Incubation of the liver VLD lipoproteins in plasma in vitro led to the transfer of about 30% of the total protein radioactivity to the HD lipoproteins. The transfer mainly involved the peak-II (arginine-rich and/or apo A-I) and peak-III (apo C) proteins. There was also a small transfer of radioactivity (about 5% of the total) to the LD lipoproteins. 4. Injection of the liver VLD lipoproteins into the circulation of the supradiaphragmatic rat resulted in the transfer of about 15% of the total VLD-lipoprotein radioactivity to the LD lipoproteins. The transfer involved mainly the peak-I (apo B) proteins and accounted for about 20% of the total apo B protein radioactivity of the injected VLD lipoproteins. When the endogenous plasma VLD lipoprotein was taken into account the transfer of apo B protein was about 35%. 5. The transfer of peak-II protein radioactivity from the VLD to the HD lipoproteins was greater in the plasma of the supradiaphragmatic rat than in the incubated plasma suggesting that there was a net transfer of peak-II apoproteins during the VLD lipoprotein degradation. The transfer of peak-III protein radioactivity was not greater in the plasma of the supradiaphragmatic rat, but there was a loss of this radioactivity from the circulation.", "contents": "The metabolic conversion of very-low-density lipoprotein into low-density lipoprotein by the extrahepatic tissues of the rat. 1. The work reported was designed to provide quantitative information about the capacity of the extrahepatic tissues of the rat to degrade injected VLD lipoproteins (very-low-density lipoproteins, d less than 1.006) to LD lipoproteins (low-density lipoproteins, d 1.006--1.063) and to study the fate of the different VLD-lipoprotein apoproteins during the degradative process. 2. Rat liver VLD lipoproteins, radioactively labelled in their protein moieties, were produced by the perfusion of the organ and were either injected into the circulation of the supradiaphragmatic rats or incubated in rat plasma at 37 degrees C. At a time (75 min) when approx. 90% of the triacylglycerol of the VLD lipoproteins had been hydrolysed the supradiaphragmatic rats were bled and VLD lipoproteins, LD lipoproteins and HD lipoproteins (high-density lipoproteins, d 1.063--1.21) were separated from their plasma and from the plasma incubated in vitro. The apoproteins of each of the lipoprotein classes were resolved by gel-filtration chromatography into three main fractions, designated peaks I, II and III. 3. Incubation of the liver VLD lipoproteins in plasma in vitro led to the transfer of about 30% of the total protein radioactivity to the HD lipoproteins. The transfer mainly involved the peak-II (arginine-rich and/or apo A-I) and peak-III (apo C) proteins. There was also a small transfer of radioactivity (about 5% of the total) to the LD lipoproteins. 4. Injection of the liver VLD lipoproteins into the circulation of the supradiaphragmatic rat resulted in the transfer of about 15% of the total VLD-lipoprotein radioactivity to the LD lipoproteins. The transfer involved mainly the peak-I (apo B) proteins and accounted for about 20% of the total apo B protein radioactivity of the injected VLD lipoproteins. When the endogenous plasma VLD lipoprotein was taken into account the transfer of apo B protein was about 35%. 5. The transfer of peak-II protein radioactivity from the VLD to the HD lipoproteins was greater in the plasma of the supradiaphragmatic rat than in the incubated plasma suggesting that there was a net transfer of peak-II apoproteins during the VLD lipoprotein degradation. The transfer of peak-III protein radioactivity was not greater in the plasma of the supradiaphragmatic rat, but there was a loss of this radioactivity from the circulation."}
{"id": "PMID:220967", "title": "Localization of oxidized nocotinamide--adenine dinucleotide glycohydrolase in the mouse liver nuclear envelope.", "content": "NAD+ glycohydrolase activity located in the nuclear envelope was maximally solubilized by treatment with 0.1--0.2% Triton X-100. The residual activity largely represents the chromatin-associated NAD+ glycohydrolase. Under these conditions the phospholipids were extensively solubilized (over 90%) while leaving the nuclei physically stable, although the nuclear membranes were removed, as shown by electron microscopy. After Triton X-100 treatment, deoxyribonuclease I did not significantly affect the residual NAD+ glycohydrolase activity, although the DNA was completely broken down. This enzyme activity can be released from the nuclear pellet by incubation with phospholipase C. For comparative studies, the glucose 6-phosphatase activity, known to be present in the nuclear envelope, was investigated. Treatment with 0.01% Triton X-100 released 10--20% of the phospholipids, but without solubilizing either glucose 6-phosphatase or NAD+ glycohydrolase. Higher Triton X-100 concentrations (0.1--1.0%) inhibited glucose 6-phosphatase, but not NAD+ glycohydrolase activity. NAD+ glycohydrolase is apparently present in a latent form in the nuclear envelope. Glucose 6-phosphatase, However, shows no such latency.", "contents": "Localization of oxidized nocotinamide--adenine dinucleotide glycohydrolase in the mouse liver nuclear envelope. NAD+ glycohydrolase activity located in the nuclear envelope was maximally solubilized by treatment with 0.1--0.2% Triton X-100. The residual activity largely represents the chromatin-associated NAD+ glycohydrolase. Under these conditions the phospholipids were extensively solubilized (over 90%) while leaving the nuclei physically stable, although the nuclear membranes were removed, as shown by electron microscopy. After Triton X-100 treatment, deoxyribonuclease I did not significantly affect the residual NAD+ glycohydrolase activity, although the DNA was completely broken down. This enzyme activity can be released from the nuclear pellet by incubation with phospholipase C. For comparative studies, the glucose 6-phosphatase activity, known to be present in the nuclear envelope, was investigated. Treatment with 0.01% Triton X-100 released 10--20% of the phospholipids, but without solubilizing either glucose 6-phosphatase or NAD+ glycohydrolase. Higher Triton X-100 concentrations (0.1--1.0%) inhibited glucose 6-phosphatase, but not NAD+ glycohydrolase activity. NAD+ glycohydrolase is apparently present in a latent form in the nuclear envelope. Glucose 6-phosphatase, However, shows no such latency."}
{"id": "PMID:220968", "title": "Fatty acid stimulation of membrane phosphatidylinositol hydrolysis by brain phosphatidylinositol phosphodiesterase.", "content": "The hydrolysis of membrane-bound phosphatidylinositol in rat liver microsomal fraction by the soluble phosphatidylinositol phosphodiesterase from rat brain was markedly stimulated by oleic acid or arachidonic acid. The stimulation did not require added calcium, although it was abolished by EDTA. Lysophosphatidylcholine also totally suppressed the stimulation. A possible role for the fatty acid content of a membrane in controlling phosphatidylinositol turnover is suggested.", "contents": "Fatty acid stimulation of membrane phosphatidylinositol hydrolysis by brain phosphatidylinositol phosphodiesterase. The hydrolysis of membrane-bound phosphatidylinositol in rat liver microsomal fraction by the soluble phosphatidylinositol phosphodiesterase from rat brain was markedly stimulated by oleic acid or arachidonic acid. The stimulation did not require added calcium, although it was abolished by EDTA. Lysophosphatidylcholine also totally suppressed the stimulation. A possible role for the fatty acid content of a membrane in controlling phosphatidylinositol turnover is suggested."}
{"id": "PMID:220988", "title": "Central nervous system lupus erythematosus: measurement of cerebrospinal fluid cyclic GMP and other clinical markers of disease activity.", "content": "Cyclic-GMP (C-GMP), a normal constituent of the central nervous system, was found to be present in increased amounts in the cerebrospinal fluid (CSF) of systemic lupus erythematosus (SLE) patients with active neurologic disease. Twenty-four CSF samples from 17 patients with SLE were evaluated for C-GMP concentration by radioimmunoassay. This study extends our initial observations and examines three groups of SLE patients based on their clinical status at the time of each lumbar puncture: those with active neurologic and psychologic abnormalities (group I), active neurologic abnormalities (group II), and psychologic abnormalities without active neurologic involvement (group III). Groups I and II had mean CSF C-GMP values of 3.1 nM +/- 0.64 (SE) and 4.1 nM +/- 0.10 respectively, which were both significantly higher than the mean for group III (1.2 nM +/- 0.43) (P less than 0.05). Other CSF findings did not display this close correlation with activity of neurologic disease. In 4 SLE patients, significantly higher levels of CSF C-GMP were found on serial sampling during times when neurologic abnormalities were active. Thus elevated CSF C-GMP concentration may be a marker of active neurologic disease in SLE.", "contents": "Central nervous system lupus erythematosus: measurement of cerebrospinal fluid cyclic GMP and other clinical markers of disease activity. Cyclic-GMP (C-GMP), a normal constituent of the central nervous system, was found to be present in increased amounts in the cerebrospinal fluid (CSF) of systemic lupus erythematosus (SLE) patients with active neurologic disease. Twenty-four CSF samples from 17 patients with SLE were evaluated for C-GMP concentration by radioimmunoassay. This study extends our initial observations and examines three groups of SLE patients based on their clinical status at the time of each lumbar puncture: those with active neurologic and psychologic abnormalities (group I), active neurologic abnormalities (group II), and psychologic abnormalities without active neurologic involvement (group III). Groups I and II had mean CSF C-GMP values of 3.1 nM +/- 0.64 (SE) and 4.1 nM +/- 0.10 respectively, which were both significantly higher than the mean for group III (1.2 nM +/- 0.43) (P less than 0.05). Other CSF findings did not display this close correlation with activity of neurologic disease. In 4 SLE patients, significantly higher levels of CSF C-GMP were found on serial sampling during times when neurologic abnormalities were active. Thus elevated CSF C-GMP concentration may be a marker of active neurologic disease in SLE."}
{"id": "PMID:220989", "title": "[The influence of clanobutin on bile secretion in the isolated perfused rat liver (author's transl)].", "content": "Isolated perfused rat liver was used to characterize the choleretic action of 4-[4-chloro-N-(4-methoxyphenyl)-benzamido]-butyric acid (clanobutin). The dose-dependent increase of the bile flow was associated with an increase of the Na+ secretion. In in vitro studies the drug inhibited the Na+-K+-ATPase of the sinusoidal membrane more than that of the canalicular membrane in a dose-dependent manner. The following hypothesis was proposed to explain the choleretic action of clanobutin. The intracellular Na+ concentration increased due to the inhibition of the sinusoidal Na+-K+-ATPase. This is then compensated by transporting the extra Na+ into the bile. However, it cannot be ruled out that Na+ is transported as counterion during hepatobiliary transport of clanobutin or else its metabolites. The effect of the drug seems to be non-specific since other enzymes of the plasma membrane were also inhibited.", "contents": "[The influence of clanobutin on bile secretion in the isolated perfused rat liver (author's transl)]. Isolated perfused rat liver was used to characterize the choleretic action of 4-[4-chloro-N-(4-methoxyphenyl)-benzamido]-butyric acid (clanobutin). The dose-dependent increase of the bile flow was associated with an increase of the Na+ secretion. In in vitro studies the drug inhibited the Na+-K+-ATPase of the sinusoidal membrane more than that of the canalicular membrane in a dose-dependent manner. The following hypothesis was proposed to explain the choleretic action of clanobutin. The intracellular Na+ concentration increased due to the inhibition of the sinusoidal Na+-K+-ATPase. This is then compensated by transporting the extra Na+ into the bile. However, it cannot be ruled out that Na+ is transported as counterion during hepatobiliary transport of clanobutin or else its metabolites. The effect of the drug seems to be non-specific since other enzymes of the plasma membrane were also inhibited."}
{"id": "PMID:220990", "title": "The action of silybin on the mouse liver in alpha-amanitine poisoning.", "content": "Histochemical and histoenzymological studies were carried out on liver slices from mice which had received alpha-amanitine two days previously, some of which had been treated with silybin, and from control mice. The toxin produced certain changes in the activity of the enzymes involved in different metabolic processes, and in the amounts of lipids and nucleic acids. Treatment with silybin, given 60 min before administering alpha-amanitine or 10 min later alike, prevents the appearance of these changes and gives results comparable to those in the control animals.", "contents": "The action of silybin on the mouse liver in alpha-amanitine poisoning. Histochemical and histoenzymological studies were carried out on liver slices from mice which had received alpha-amanitine two days previously, some of which had been treated with silybin, and from control mice. The toxin produced certain changes in the activity of the enzymes involved in different metabolic processes, and in the amounts of lipids and nucleic acids. Treatment with silybin, given 60 min before administering alpha-amanitine or 10 min later alike, prevents the appearance of these changes and gives results comparable to those in the control animals."}
{"id": "PMID:220991", "title": "A new and rapid system for the determination of enzymatic activity of bacterial collagenases.", "content": "Collagenase activity is assayed using N-CBZ-Gly-Pro-Gly-Pro-Ala as substrate in an autoanalyzer II system. The liberation of the tripeptide is monitored after the reaction with trinitrobenzenesulfonic acid. The new system shows a considerably improved precision when compared to existing methods and allows about ten times as many samples to be analyzed per day. This is of importance for laboratories where large amounts of activity determinations have to be performed.", "contents": "A new and rapid system for the determination of enzymatic activity of bacterial collagenases. Collagenase activity is assayed using N-CBZ-Gly-Pro-Gly-Pro-Ala as substrate in an autoanalyzer II system. The liberation of the tripeptide is monitored after the reaction with trinitrobenzenesulfonic acid. The new system shows a considerably improved precision when compared to existing methods and allows about ten times as many samples to be analyzed per day. This is of importance for laboratories where large amounts of activity determinations have to be performed."}
{"id": "PMID:220994", "title": "Different appearance of hepatic collagenase and lysosomal enzymes in recovery of experimental hepatic fibrosis.", "content": "1. Both activities of hepatic collagenase and lysosomal enzymes (acid phosphatase, beta-glucuronidase and N-acetyl-beta-D-glucosaminidase) have been observed in the recovery from experimental hepatic fibrosis in rats treated with carbon tetrachloride for 6 to 20 weeks, and compared with the disappearance of newly formed collagen fibers in the recovery process. 2. In the process of experimental hepatic fibrosis, collagenase activity reached maximum on sethe accumulation of collagen fibers in reversible hepatic fibrosis, but decreased to the same level as that of non-treated rat liver in cirrhotic stage. In the reocvery from reversible hepatic fibrosis, collagenase activity reached maximum on second day after the discontinuation of carbon tetrachloride, and decreased to the same extent of that of non-treated rat liver on seventh day. 3. Lysosomal enzyme activity was parallel to the activity of hepatic collagenase and to the accumulation of collagen fibers in the process of hepatic fibrosis. In the recovery stage, lysosomal enzyme activity in mesenchymal cells within the septa increased markedly on second day after the discontinuation of toxic agent but turned to the same level of that of non-treated rat liver seven days later, which was consistent with the appearance and disappearance of collagenase activity. On the other hand the appearance of lysosomal enzymes activities in Kupffer cells and hepatocytes was different from that of collagenase activity. That is lysosomal enzyme activity in Kupffer cells decreased in early days but increased five days later, and the enzyme activity in hepatocytes markedly decreased but gradually recovered to normal level seven days later. 4. The appearance of collagenase was observed at the beginning of the recovery stage. It indicates that mammalian collagenase initiates the collagen degradation and lysosomal enzymes might have a role in the subsequent degradation of collagen.", "contents": "Different appearance of hepatic collagenase and lysosomal enzymes in recovery of experimental hepatic fibrosis. 1. Both activities of hepatic collagenase and lysosomal enzymes (acid phosphatase, beta-glucuronidase and N-acetyl-beta-D-glucosaminidase) have been observed in the recovery from experimental hepatic fibrosis in rats treated with carbon tetrachloride for 6 to 20 weeks, and compared with the disappearance of newly formed collagen fibers in the recovery process. 2. In the process of experimental hepatic fibrosis, collagenase activity reached maximum on sethe accumulation of collagen fibers in reversible hepatic fibrosis, but decreased to the same level as that of non-treated rat liver in cirrhotic stage. In the reocvery from reversible hepatic fibrosis, collagenase activity reached maximum on second day after the discontinuation of carbon tetrachloride, and decreased to the same extent of that of non-treated rat liver on seventh day. 3. Lysosomal enzyme activity was parallel to the activity of hepatic collagenase and to the accumulation of collagen fibers in the process of hepatic fibrosis. In the recovery stage, lysosomal enzyme activity in mesenchymal cells within the septa increased markedly on second day after the discontinuation of toxic agent but turned to the same level of that of non-treated rat liver seven days later, which was consistent with the appearance and disappearance of collagenase activity. On the other hand the appearance of lysosomal enzymes activities in Kupffer cells and hepatocytes was different from that of collagenase activity. That is lysosomal enzyme activity in Kupffer cells decreased in early days but increased five days later, and the enzyme activity in hepatocytes markedly decreased but gradually recovered to normal level seven days later. 4. The appearance of collagenase was observed at the beginning of the recovery stage. It indicates that mammalian collagenase initiates the collagen degradation and lysosomal enzymes might have a role in the subsequent degradation of collagen."}
{"id": "PMID:220995", "title": "Effect of starvation, alloxan diabetes and adrenalectomy on Na+ K+-ATPase of the mucosa of the small intestine of rat.", "content": "The dietary stress conditions such as starvation influenced Na+K+-ATPase activity which increased steadily above normal fed levels between the starvation periods of 24--48 hr. Also, an increased enzyme level was observed in alloxan diabetic rats and administration of insulin to diabetic rats led to a tendency towards a lowering of Na+K+-ATPase. Adrenalectomy brought about a lowering of Na+K+-ATPase activity from those of normals while the administration of hydrocortisone induced an enhancement. The results indicate that both starvation and diabetic conditions might cause a stress-like activation of adrenal cortex resulting in increased levels of glucocorticoids which in turn activate the intestinal Na+K+-ATPase activity.", "contents": "Effect of starvation, alloxan diabetes and adrenalectomy on Na+ K+-ATPase of the mucosa of the small intestine of rat. The dietary stress conditions such as starvation influenced Na+K+-ATPase activity which increased steadily above normal fed levels between the starvation periods of 24--48 hr. Also, an increased enzyme level was observed in alloxan diabetic rats and administration of insulin to diabetic rats led to a tendency towards a lowering of Na+K+-ATPase. Adrenalectomy brought about a lowering of Na+K+-ATPase activity from those of normals while the administration of hydrocortisone induced an enhancement. The results indicate that both starvation and diabetic conditions might cause a stress-like activation of adrenal cortex resulting in increased levels of glucocorticoids which in turn activate the intestinal Na+K+-ATPase activity."}
{"id": "PMID:220998", "title": "The mechanism of photodynamic inactivation of human cells in vitro in the presence of haematoporphyrin.", "content": "The photosensitizing effect of haematoporphyrin (HP) on human cells of the established line NHIK 3025 has been studied. Fluorescence measurements show that HP is bound to these cells. Serum proteins also bind HP, and the presence of 10% human serum during incubation with HP (3 X 10(-4)M) reduces the cellular uptake of HP by 75% or more. The photosensitized inactivation is enhanced when the cells are suspended in D2O-buffer during irradiation. This indicates that singlet oxygen is involved in the inactivation. Two findings indicate that the photoinduced damage is repairable: firstly, the fraction of cells surviving a given light dose decreases with decreasing irradiation temperature, and secondly, the survival curves have a shoulder at low exposures of light.", "contents": "The mechanism of photodynamic inactivation of human cells in vitro in the presence of haematoporphyrin. The photosensitizing effect of haematoporphyrin (HP) on human cells of the established line NHIK 3025 has been studied. Fluorescence measurements show that HP is bound to these cells. Serum proteins also bind HP, and the presence of 10% human serum during incubation with HP (3 X 10(-4)M) reduces the cellular uptake of HP by 75% or more. The photosensitized inactivation is enhanced when the cells are suspended in D2O-buffer during irradiation. This indicates that singlet oxygen is involved in the inactivation. Two findings indicate that the photoinduced damage is repairable: firstly, the fraction of cells surviving a given light dose decreases with decreasing irradiation temperature, and secondly, the survival curves have a shoulder at low exposures of light."}
{"id": "PMID:220999", "title": "Retrovirus-like particles in EBV-negative Burkitt's lymphoma cell line but not in EBV-DNA-positive lines from patients with ataxia telangiectasia and Down's syndrome.", "content": "Retrovirus-like particles can be recovered by arginine deprivation from the BJAB-1 Epstein-Barr virus (EBV) negative cell line derived from an African patient with typical Burkitt's lymphoma. These particles resemble retroviruses in their morphology and in their physicochemical properties. Particles with a similar morphology were obtained from derivative cell lines established by infecting BJAB-1 cells with EBV. On the other hand, retrovirus-like particles could not be induced in EBV-DNA-positive lymphoblastoid cell lines derived from non-leukaemic patients with ataxia telangiectasia and Down's syndrome and from a patient with infectious mononucleosis.", "contents": "Retrovirus-like particles in EBV-negative Burkitt's lymphoma cell line but not in EBV-DNA-positive lines from patients with ataxia telangiectasia and Down's syndrome. Retrovirus-like particles can be recovered by arginine deprivation from the BJAB-1 Epstein-Barr virus (EBV) negative cell line derived from an African patient with typical Burkitt's lymphoma. These particles resemble retroviruses in their morphology and in their physicochemical properties. Particles with a similar morphology were obtained from derivative cell lines established by infecting BJAB-1 cells with EBV. On the other hand, retrovirus-like particles could not be induced in EBV-DNA-positive lymphoblastoid cell lines derived from non-leukaemic patients with ataxia telangiectasia and Down's syndrome and from a patient with infectious mononucleosis."}
{"id": "PMID:221000", "title": "Antibody-induced changes in levels of cyclic adenosine monophosphate in leukaemic lymphocytes.", "content": "When L2C leukaemic B lymphocytes from guinea-pigs were incubated in vitro with antibody directed to their surface immunoglobulin (Ig), a rapid rise in intracellular adenosine 3':5'-phosphate (cyclic adenosine monophosphate, cAMP) was observed. Estimation of cAMP was by a protein-binding assay using bovine adrenal protein kinase. Increases up to 30-fold occurred within 30 seconds of incubation at 37 degrees C, to be succeeded by a fall which reached the basal level between 5 and 7 min. The response was proportional to the amount of antibody present. Cross-linking of surface Ig by the antibody was necessary, bivalent (Fab'gamma)2 from the antibody gave a rise in cAMP similar to that given by the parent molecule, whereas monomeric Fab'gamma was ineffective unless it was subsequently cross-linked by anti-antibody. The rise was too rapid to have required capping of the surface Ig for its induction. Not all perturbations of the plasma membrane by antibody induce such a surge in cAMP, since anti-beta2 microglobulin, also reacting with the lymphocyte surface, failed to alter cAMP concentration. The results emphasize that immunotherapy can be influenced by antibody altering the metabolic activity of target cells, quite apart from activation of immunological cytotoxic pathways.", "contents": "Antibody-induced changes in levels of cyclic adenosine monophosphate in leukaemic lymphocytes. When L2C leukaemic B lymphocytes from guinea-pigs were incubated in vitro with antibody directed to their surface immunoglobulin (Ig), a rapid rise in intracellular adenosine 3':5'-phosphate (cyclic adenosine monophosphate, cAMP) was observed. Estimation of cAMP was by a protein-binding assay using bovine adrenal protein kinase. Increases up to 30-fold occurred within 30 seconds of incubation at 37 degrees C, to be succeeded by a fall which reached the basal level between 5 and 7 min. The response was proportional to the amount of antibody present. Cross-linking of surface Ig by the antibody was necessary, bivalent (Fab'gamma)2 from the antibody gave a rise in cAMP similar to that given by the parent molecule, whereas monomeric Fab'gamma was ineffective unless it was subsequently cross-linked by anti-antibody. The rise was too rapid to have required capping of the surface Ig for its induction. Not all perturbations of the plasma membrane by antibody induce such a surge in cAMP, since anti-beta2 microglobulin, also reacting with the lymphocyte surface, failed to alter cAMP concentration. The results emphasize that immunotherapy can be influenced by antibody altering the metabolic activity of target cells, quite apart from activation of immunological cytotoxic pathways."}
{"id": "PMID:221001", "title": "Effect of mouse hepatitis virus infection on iron retention in the mouse liver.", "content": "Increased iron uptake and iron-induced ferritin synthesis has been demonstrated in experimentally virus-infected cell cultures. However, this has not been observed in the intact animal. The results reported in this paper indicate that higher deposition of injected radioiron occurs in the livers of mice infected with MHV-3 virus compared with livers from uninfected animals. Administration of iron at different time intervals indicated that iron uptake correlates well with the degree of tissue injury in the livers of infected animals.", "contents": "Effect of mouse hepatitis virus infection on iron retention in the mouse liver. Increased iron uptake and iron-induced ferritin synthesis has been demonstrated in experimentally virus-infected cell cultures. However, this has not been observed in the intact animal. The results reported in this paper indicate that higher deposition of injected radioiron occurs in the livers of mice infected with MHV-3 virus compared with livers from uninfected animals. Administration of iron at different time intervals indicated that iron uptake correlates well with the degree of tissue injury in the livers of infected animals."}
{"id": "PMID:221002", "title": "Cellular heterogeneity in an ethylnitrosourea-induced glioma: malignancy, karyology and other properties of tumour cell types.", "content": "Two types of tumour cell have been obtained from a glioma transplacentally induced by ethylnitrosourea in a BD-IX rat. These were distinguished in culture by their different morphologies, responses to dibutyryl cyclic adenosine monophosphate, inducibility of glycerol phosphate dehydrogenase and growth in soft agar. They had different karyotypes, with distinctive numbers and arrangements of chromosomes. One cell type had an apparently normal diploid set of 42 whilst the other had 43 chromosomes. An additional chromosome No 4 was identified in the latter by Giemsa banding. Translocations and other abnormalities involving this chromosome were consistently observed. Both cell types produced malignant, astrocytic tumours when injected into newborn syngeneic rats, but with different latent periods and morphological features.", "contents": "Cellular heterogeneity in an ethylnitrosourea-induced glioma: malignancy, karyology and other properties of tumour cell types. Two types of tumour cell have been obtained from a glioma transplacentally induced by ethylnitrosourea in a BD-IX rat. These were distinguished in culture by their different morphologies, responses to dibutyryl cyclic adenosine monophosphate, inducibility of glycerol phosphate dehydrogenase and growth in soft agar. They had different karyotypes, with distinctive numbers and arrangements of chromosomes. One cell type had an apparently normal diploid set of 42 whilst the other had 43 chromosomes. An additional chromosome No 4 was identified in the latter by Giemsa banding. Translocations and other abnormalities involving this chromosome were consistently observed. Both cell types produced malignant, astrocytic tumours when injected into newborn syngeneic rats, but with different latent periods and morphological features."}
{"id": "PMID:221006", "title": "Mechanism of Lactobacillus leichmannii ribonucleotide reductase studied with Coalpha-[alpha-(Aden-9-yl)]-Cobeta-adenosylcobamide (Pseudocoenzyme B12) as coenzyme.", "content": "Coalpha-[alpha-(Aden-9-yl)]-Cobeta-adenosylcobamide (pseudocoenzyme B12) purified from Clostridium tetanomorphum has been reacted with ribonucleotide reductase purified from Lactobacillus leichmannii under various conditions, and the properties of the products obtained have been compared by electron paramagnetic resonance (EPR) with those previously reported for products formed from the normal coenzyme (adenosylcobalamin). The rapidly formed intermediate and the slowly formed \"doublet\" species from the pseudocoenzyme have EPR spectra identical with those formed from the normal coenzyme. This and other considerations make it less likely that the unusual magnetic properties of the rapidly formed intermediate are due to strongly distorted octahedral symmetry about Co(II) as previously postulated. Instead it is probable that the EPR spectrum is due to interaction of the radical pair by both exchange coupling and magnetic dipole--dipole coupling. Although Coalpha-[alpha-(aden-9-YL)]cob(II)amide in solution does not show superhyperfine splitting in the EPR spectrum because of its base-off configuration, the cob(II)amide formed by degradation of the pseudocoenzyme within the catalytic site of the enzyme did show triplets due to a nitrogen axially coordinated to cobalt. This suggests that binding of the cob(II)amide to the reductase catalytic site causes a shift to the base-on form.", "contents": "Mechanism of Lactobacillus leichmannii ribonucleotide reductase studied with Coalpha-[alpha-(Aden-9-yl)]-Cobeta-adenosylcobamide (Pseudocoenzyme B12) as coenzyme. Coalpha-[alpha-(Aden-9-yl)]-Cobeta-adenosylcobamide (pseudocoenzyme B12) purified from Clostridium tetanomorphum has been reacted with ribonucleotide reductase purified from Lactobacillus leichmannii under various conditions, and the properties of the products obtained have been compared by electron paramagnetic resonance (EPR) with those previously reported for products formed from the normal coenzyme (adenosylcobalamin). The rapidly formed intermediate and the slowly formed \"doublet\" species from the pseudocoenzyme have EPR spectra identical with those formed from the normal coenzyme. This and other considerations make it less likely that the unusual magnetic properties of the rapidly formed intermediate are due to strongly distorted octahedral symmetry about Co(II) as previously postulated. Instead it is probable that the EPR spectrum is due to interaction of the radical pair by both exchange coupling and magnetic dipole--dipole coupling. Although Coalpha-[alpha-(aden-9-YL)]cob(II)amide in solution does not show superhyperfine splitting in the EPR spectrum because of its base-off configuration, the cob(II)amide formed by degradation of the pseudocoenzyme within the catalytic site of the enzyme did show triplets due to a nitrogen axially coordinated to cobalt. This suggests that binding of the cob(II)amide to the reductase catalytic site causes a shift to the base-on form."}
{"id": "PMID:221010", "title": "Membrane glycopeptides from virus-transformed hamster fibroblasts and the normal counterpart.", "content": "Comparisons of membrane glycopeptides from baby hamster kidney fibroblasts (BHK21/C13) and a clone transformed by Rous sarcoma virus (C13/B4) were made by using cells metabolically labeled with radioactive D-glucose and L-fucose. Most of the glycopeptides were metabolically labeled with both the general and the specific glycoprotein precursors. The glycopeptides obtained from the cell surface by controlled trypsinization were representative of the surface membrane as shown by comparing them with those of purified membrane preparations. The trypsin-removable glycopeptides from both cell types were further processed and examined by successive chromatography on Sephadex G-50 and DEAE-cellulose. The chromatographic distribution patterns showed that each cell type had glycopeptides of similar characteristics, although the proportions of the glycopeptides differed dramatically between the two cell types. After transformation there was an increase in the larger, more highly charged glycopeptides. This was verified by the increased sialic acid content in these glycopeptides. Some of the glycopeptides were homogeneous after the size and charge separations, since a variety of procedures did not separate them further. The apparent homogeneity and reasonably few species obtained may be due to the methods of isolation, with the procedures selecting particular glycopeptides from the external portion of the membrane. These results corroborate the concept and show for the first time that virus transformation is accompanied by an increase in certain species of glycopeptides rather than de novo synthesis.", "contents": "Membrane glycopeptides from virus-transformed hamster fibroblasts and the normal counterpart. Comparisons of membrane glycopeptides from baby hamster kidney fibroblasts (BHK21/C13) and a clone transformed by Rous sarcoma virus (C13/B4) were made by using cells metabolically labeled with radioactive D-glucose and L-fucose. Most of the glycopeptides were metabolically labeled with both the general and the specific glycoprotein precursors. The glycopeptides obtained from the cell surface by controlled trypsinization were representative of the surface membrane as shown by comparing them with those of purified membrane preparations. The trypsin-removable glycopeptides from both cell types were further processed and examined by successive chromatography on Sephadex G-50 and DEAE-cellulose. The chromatographic distribution patterns showed that each cell type had glycopeptides of similar characteristics, although the proportions of the glycopeptides differed dramatically between the two cell types. After transformation there was an increase in the larger, more highly charged glycopeptides. This was verified by the increased sialic acid content in these glycopeptides. Some of the glycopeptides were homogeneous after the size and charge separations, since a variety of procedures did not separate them further. The apparent homogeneity and reasonably few species obtained may be due to the methods of isolation, with the procedures selecting particular glycopeptides from the external portion of the membrane. These results corroborate the concept and show for the first time that virus transformation is accompanied by an increase in certain species of glycopeptides rather than de novo synthesis."}
{"id": "PMID:221011", "title": "Partial structure of a membrane glycopeptide from virus-transformed hamster cells.", "content": "The predominant surface glycopeptide from a clone of baby hamster kidney cells transformed by Rous sarcoma virus (C13/B4), metabolically labeled with L-[14C]fucose, has been characterized for the first time. This glycopeptide represents 19% of the total radioactivity removed by trypsin from the cell surface of the transformed fibroblasts and is more abundant in the transformed cells than in the normal counterpart. Purification of the glycopeptide after digestion with Pronase was by successive chromatography on DEAE-cellulose and Sephadex G-50. The monosaccharide content of the glycopeptide was 42, 127, 138, 114, and 243 nmol of fucose, sialic acid, galatose, mannose, and glucosamine, respectively. A partial structure of the glycopeptide was proposed from the results of sequential enzymatic degradation coupled with gas-liquid chromatographic analysis of the resultant monosaccharides. All of the enzymes used were purified and pretested on natural substrates and found to remove terminal monosaccharides of the correct configuration, quantitatively. The purification and properties of an alpha-L-fucosidase from rat testes were described. All of the radioactivity in the glycopeptide, recovered as fucose, was present at the core and was removed by treatment with this alpha-L-fucosidase. The proposed structure is a triantennary, completely sialylated, complex glycopeptide containing a core region of beta-D-mannose, beta-D-N-acetylglucosamine, and alpha-L-fucose.", "contents": "Partial structure of a membrane glycopeptide from virus-transformed hamster cells. The predominant surface glycopeptide from a clone of baby hamster kidney cells transformed by Rous sarcoma virus (C13/B4), metabolically labeled with L-[14C]fucose, has been characterized for the first time. This glycopeptide represents 19% of the total radioactivity removed by trypsin from the cell surface of the transformed fibroblasts and is more abundant in the transformed cells than in the normal counterpart. Purification of the glycopeptide after digestion with Pronase was by successive chromatography on DEAE-cellulose and Sephadex G-50. The monosaccharide content of the glycopeptide was 42, 127, 138, 114, and 243 nmol of fucose, sialic acid, galatose, mannose, and glucosamine, respectively. A partial structure of the glycopeptide was proposed from the results of sequential enzymatic degradation coupled with gas-liquid chromatographic analysis of the resultant monosaccharides. All of the enzymes used were purified and pretested on natural substrates and found to remove terminal monosaccharides of the correct configuration, quantitatively. The purification and properties of an alpha-L-fucosidase from rat testes were described. All of the radioactivity in the glycopeptide, recovered as fucose, was present at the core and was removed by treatment with this alpha-L-fucosidase. The proposed structure is a triantennary, completely sialylated, complex glycopeptide containing a core region of beta-D-mannose, beta-D-N-acetylglucosamine, and alpha-L-fucose."}
{"id": "PMID:221012", "title": "Ubiquinone in Rhodopseudomonas sphaeroides. Some thermodynamic properties.", "content": "In Rhodopseudomonas sphaeroides chromatophores there are 25 +/- 3 ubiquinone (Q) molecules/reaction center protein. They comprise several thermodynamically and functionally different ubiquinone complements. There are approx. 19 ubiquinones (Em7 = 90 mV) in the main ubiquinone complement which, within experimental resolution, appears thermodynamically homogenous and follows the redox reaction Q + 2e + 2H+ in equilibrium with QH2 from pH 5--9. A method which takes advantage of the 2H+ bound/molecule of Q reduced is described for measuring the time course of light-activated reaction center-driven reduction and oxidation of the 19 Q complement. No stable semiquinones were detected in the constitutents of the 19 Q complement. There are approx. 6 ubiquinones of lower Em which are currently unaccounted for, although one or possibly two of these can be assigned to the quinones of the reaction center protein. The remainder may be associated with the NADH-ubiquinone oxidoreductase.", "contents": "Ubiquinone in Rhodopseudomonas sphaeroides. Some thermodynamic properties. In Rhodopseudomonas sphaeroides chromatophores there are 25 +/- 3 ubiquinone (Q) molecules/reaction center protein. They comprise several thermodynamically and functionally different ubiquinone complements. There are approx. 19 ubiquinones (Em7 = 90 mV) in the main ubiquinone complement which, within experimental resolution, appears thermodynamically homogenous and follows the redox reaction Q + 2e + 2H+ in equilibrium with QH2 from pH 5--9. A method which takes advantage of the 2H+ bound/molecule of Q reduced is described for measuring the time course of light-activated reaction center-driven reduction and oxidation of the 19 Q complement. No stable semiquinones were detected in the constitutents of the 19 Q complement. There are approx. 6 ubiquinones of lower Em which are currently unaccounted for, although one or possibly two of these can be assigned to the quinones of the reaction center protein. The remainder may be associated with the NADH-ubiquinone oxidoreductase."}
{"id": "PMID:221013", "title": "Studies on the molecular organization of cytochromes P-450 and b5 in the microsomal membrane.", "content": "1. The relative orientations of the heme groups of cytochromes P-450 and b5 in the microsomal membrane have been studied by the technique of electron paramagnetic resonance. The results show that the heme plane of cytochrome P-450 lies in the same plane as the membrane surface, whereas the cytochrome b5 heme plane has a random orientation. 2. No significant broadening or change in relaxation properties of the gz component of low spin cytochrome P-450 occurred when cytochrome b5 was reduced by redox poising. It is concluded that there is little or no paramagnetic coupling between the heme groups of the two species. 3. The results favor a model in which no tight complex between cytochromes P-450 and b5 is present, the species being independent and interacting only by random molecular collisions or via other intermediate species.", "contents": "Studies on the molecular organization of cytochromes P-450 and b5 in the microsomal membrane. 1. The relative orientations of the heme groups of cytochromes P-450 and b5 in the microsomal membrane have been studied by the technique of electron paramagnetic resonance. The results show that the heme plane of cytochrome P-450 lies in the same plane as the membrane surface, whereas the cytochrome b5 heme plane has a random orientation. 2. No significant broadening or change in relaxation properties of the gz component of low spin cytochrome P-450 occurred when cytochrome b5 was reduced by redox poising. It is concluded that there is little or no paramagnetic coupling between the heme groups of the two species. 3. The results favor a model in which no tight complex between cytochromes P-450 and b5 is present, the species being independent and interacting only by random molecular collisions or via other intermediate species."}
{"id": "PMID:221014", "title": "The multiplicity and stoichiometry of the prosthetic groups in QH2: cytochrome c oxidoreductase as studied by EPR.", "content": "1. The EPR signal in the g = 2 region of the reduced QH2: cytochrome c oxidoreductase as present in submitochondrial particles and the isolated enzyme is an overlap of two signals in a 1 : 1 weighted ratio. Both signals are due to [2Fe-2S]+1 centers. 2. From the signal intensity it is computed that the concentration of each Fe-S center is half that of cytochrome c1. 3. The line shape of one of the Fe-S centers, defined as center 1, is reversibly dependent on the redox state of the b-c1 complex. The change of the line shape cannot be correlated with changes of the redox state of any of the cytochromes in QH2: cytochrome c oxidoreductase. 4. Lie the optical spectrum, the EPR spectrum of the cytochromes is composed of the absorption of at least three different b cytochromes and cytochrome c1. 5. The molar ratio of the prosthetic groups was found to be c1 : b-562 : b-566 : b-558 : center 1 : center 2 = 2 : 2 : 1 : 1 : 1 : 1. The consequences of this stoichiometry are discussed in relation to the basic enzymic unit of QH2 : cytochrome c oxidoreductase.", "contents": "The multiplicity and stoichiometry of the prosthetic groups in QH2: cytochrome c oxidoreductase as studied by EPR. 1. The EPR signal in the g = 2 region of the reduced QH2: cytochrome c oxidoreductase as present in submitochondrial particles and the isolated enzyme is an overlap of two signals in a 1 : 1 weighted ratio. Both signals are due to [2Fe-2S]+1 centers. 2. From the signal intensity it is computed that the concentration of each Fe-S center is half that of cytochrome c1. 3. The line shape of one of the Fe-S centers, defined as center 1, is reversibly dependent on the redox state of the b-c1 complex. The change of the line shape cannot be correlated with changes of the redox state of any of the cytochromes in QH2: cytochrome c oxidoreductase. 4. Lie the optical spectrum, the EPR spectrum of the cytochromes is composed of the absorption of at least three different b cytochromes and cytochrome c1. 5. The molar ratio of the prosthetic groups was found to be c1 : b-562 : b-566 : b-558 : center 1 : center 2 = 2 : 2 : 1 : 1 : 1 : 1. The consequences of this stoichiometry are discussed in relation to the basic enzymic unit of QH2 : cytochrome c oxidoreductase."}
{"id": "PMID:221015", "title": "Intensity of highly anisotropic low-spin heme EPR signals.", "content": "A semi-empirical formula has been derived to calculate the concentration of low-spin heme compounds that are highly anisotropic, i.e. 3 less than gz less than 4, and where information only on the gz absorption is available.", "contents": "Intensity of highly anisotropic low-spin heme EPR signals. A semi-empirical formula has been derived to calculate the concentration of low-spin heme compounds that are highly anisotropic, i.e. 3 less than gz less than 4, and where information only on the gz absorption is available."}
{"id": "PMID:221016", "title": "Studies on antiviral glycosides. II. Mode of action for virucidal effects on Sendai virus.", "content": "Treatment of Sendai virus with p-(sec-butyl)-phenyl-6-chloro-6-deoxy-beta-D-glucopyranoside, followed by freezing and thawing resulted in a loss of hemolytic and cell fusion activities as well as infectivity without affecting hemagglutinating and neuraminidase activities. The anti-hemolytic activity of this compound was reversed by the addition of phosphatidyl choline to the virus samples. p-Azidophenyl-6-chloro-6-deoxy-beta-D[3H]glucopyranoside was successfully used for photoaffinity labeling of a specific virion site, and we confirmed the affected site of the glucoside to be the lipid components in the viral envelopes.", "contents": "Studies on antiviral glycosides. II. Mode of action for virucidal effects on Sendai virus. Treatment of Sendai virus with p-(sec-butyl)-phenyl-6-chloro-6-deoxy-beta-D-glucopyranoside, followed by freezing and thawing resulted in a loss of hemolytic and cell fusion activities as well as infectivity without affecting hemagglutinating and neuraminidase activities. The anti-hemolytic activity of this compound was reversed by the addition of phosphatidyl choline to the virus samples. p-Azidophenyl-6-chloro-6-deoxy-beta-D[3H]glucopyranoside was successfully used for photoaffinity labeling of a specific virion site, and we confirmed the affected site of the glucoside to be the lipid components in the viral envelopes."}
{"id": "PMID:221017", "title": "Effects of microtubule-disruptive and membrane-stabilizing agents on low density lipoprotein metabolism by cultured human fibroblasts.", "content": "The cellular mechanisms involved in the uptake and metabolism of low density lipoprotein (LDL) by cultured normal human fibroblasts have been investigated with the aid of drugs known to disrupt cytoplasmic microtubules or to inhibit membrane fusion. Two drugs which disrupt microtubules by differing mechanisms, colchicine and vinblastine, each reduced the high affinity surface binding of 125I-labelled LDL by fibroblasts. Associated reductions of the endocytosis and degradation of the lipoprotein could be attributed almost entirely to this effect. In contrast, lumicolchicine, an analogue of colchicine without microtubule-disruptive activity, had little or no effect on 125I-labelled LDL metabolism. Each of two groups of membrane-stabilizing agents, the phenothiazines and the tertiary amine local anaesthetics, directly inhibited both the internalization of 125I-labelled LDL following high affinity binding to cell surface receptors and the catabolism of the lipoprotein subsequent to endocytosis, supporting previous morphological evidence for the importance of membrane fusion in these processes.", "contents": "Effects of microtubule-disruptive and membrane-stabilizing agents on low density lipoprotein metabolism by cultured human fibroblasts. The cellular mechanisms involved in the uptake and metabolism of low density lipoprotein (LDL) by cultured normal human fibroblasts have been investigated with the aid of drugs known to disrupt cytoplasmic microtubules or to inhibit membrane fusion. Two drugs which disrupt microtubules by differing mechanisms, colchicine and vinblastine, each reduced the high affinity surface binding of 125I-labelled LDL by fibroblasts. Associated reductions of the endocytosis and degradation of the lipoprotein could be attributed almost entirely to this effect. In contrast, lumicolchicine, an analogue of colchicine without microtubule-disruptive activity, had little or no effect on 125I-labelled LDL metabolism. Each of two groups of membrane-stabilizing agents, the phenothiazines and the tertiary amine local anaesthetics, directly inhibited both the internalization of 125I-labelled LDL following high affinity binding to cell surface receptors and the catabolism of the lipoprotein subsequent to endocytosis, supporting previous morphological evidence for the importance of membrane fusion in these processes."}
{"id": "PMID:221018", "title": "Isolation of luminal and antiluminal membranes from dog kidney cortex.", "content": "Luminal (brush border) and antiluminal (basal-lateral) membranes were isolated from canine renal cortex. The enzyme marker for luminal membrane, alkaline phosphatase was enhanced 19-fold and the antiluminal enzyme marker, (Na+ + K+)-ATPase, was enhanced 22-fold in their respective membrane preparation, while the amount of cross contamination was minimal. Contamination of these preparations by enzyme markers for lysosomes, endoplasmic reticulum and mitochondria was also low. Routinely, more than 50 mg membrane protein was isolated for each membrane. Electron micrographs showed that the membranes were uniform in size, appearance, and vesicular in nature. An examination of the orientation of these membranes showed that 76.5% of the antiluminal membranes and 86% of the luminal membranes were right-side out.", "contents": "Isolation of luminal and antiluminal membranes from dog kidney cortex. Luminal (brush border) and antiluminal (basal-lateral) membranes were isolated from canine renal cortex. The enzyme marker for luminal membrane, alkaline phosphatase was enhanced 19-fold and the antiluminal enzyme marker, (Na+ + K+)-ATPase, was enhanced 22-fold in their respective membrane preparation, while the amount of cross contamination was minimal. Contamination of these preparations by enzyme markers for lysosomes, endoplasmic reticulum and mitochondria was also low. Routinely, more than 50 mg membrane protein was isolated for each membrane. Electron micrographs showed that the membranes were uniform in size, appearance, and vesicular in nature. An examination of the orientation of these membranes showed that 76.5% of the antiluminal membranes and 86% of the luminal membranes were right-side out."}
{"id": "PMID:221019", "title": "Spin-label studies of membrane-associated denatured hemoglobin in normal and sickle cells.", "content": "A maleimide spin label (N-(1-oxyl-2,2,5,5-tetramethylpyrrolidinyl)-maleimide) was reacted with oxyhemoglobin-free cell stromata of normal and sickle cells. The EPR spectrum of spin-labeled red cell membranes showed that the spin labels are attached to at least two different binding sites. There was a major signal, A, which characterized a strongly immobilized environment and a minor signal, B, which characterized a weakly immobilized environment. Quantitative EPR measurements using equal amounts of Hb AA and Hb SS red blood cells demonstrated that Hb SS red cell membranes had an approximately four times higher EPR signal intensity than Hb AA red cell membranes ((7.98 +/- 1.14 . 10(5) and (2.2 +/- 1.2) . 10(5) spin labels/cell, respectively). Moreover, the ratio of signal intensities A and B are different in these cells. Comparative spectrophotometric studies of membrane-associated denatured hemoglobins of Hb AA and Hb SS red cell membranes suggested that the EPR signal A is derived from spin labels attached to membrane-associated denatured hemoglobin, while signal B is mainly from spin labels attached to membranes. The combination of EPR spectrum of Hb AA membranes pretreated with N-ethylmaleimide and that of spin-labeled precipitated hemoglobin further strengthened this conclusion.", "contents": "Spin-label studies of membrane-associated denatured hemoglobin in normal and sickle cells. A maleimide spin label (N-(1-oxyl-2,2,5,5-tetramethylpyrrolidinyl)-maleimide) was reacted with oxyhemoglobin-free cell stromata of normal and sickle cells. The EPR spectrum of spin-labeled red cell membranes showed that the spin labels are attached to at least two different binding sites. There was a major signal, A, which characterized a strongly immobilized environment and a minor signal, B, which characterized a weakly immobilized environment. Quantitative EPR measurements using equal amounts of Hb AA and Hb SS red blood cells demonstrated that Hb SS red cell membranes had an approximately four times higher EPR signal intensity than Hb AA red cell membranes ((7.98 +/- 1.14 . 10(5) and (2.2 +/- 1.2) . 10(5) spin labels/cell, respectively). Moreover, the ratio of signal intensities A and B are different in these cells. Comparative spectrophotometric studies of membrane-associated denatured hemoglobins of Hb AA and Hb SS red cell membranes suggested that the EPR signal A is derived from spin labels attached to membrane-associated denatured hemoglobin, while signal B is mainly from spin labels attached to membranes. The combination of EPR spectrum of Hb AA membranes pretreated with N-ethylmaleimide and that of spin-labeled precipitated hemoglobin further strengthened this conclusion."}
{"id": "PMID:221020", "title": "Monitoring the location profile of fluorophores in phosphatidylcholine bilayers by the use or paramagnetic quenching.", "content": "Spin probes differing in the position of their paramagnetic centre are used to quench the fluorescence of pyrene derivatives and chlorophylls incorporated into dimyristoyl phosphatidylcholine membranes. Pyrene butyric acid and pyrene decanoic acid with known orientation relative to the membrane surface are investigated. The quenching efficiency of fatty acid spin probes is dependent on the position of the nitroxide radical group in the fatty acid chain. Using this short range interaction we developed a spectroscopic method to chlorophyll-containing vesicles, we were able to characterize the orientation of the porphyrin ring within the membrane. Moreover, the chlorophyll fluorescence is also quenched by a water-soluble spin label. Therefore the porphyrin ring appears to be orientated in the polar head group region of the lipid layer, but not to be protruding out into the water phase. This conclusion is confirmed by the use of pyrene derivatives. Fluorescence quenching by a water-soluble spin label within the lipid matrix is observed even in the rigid state of the membrane. Fluorescence lifetime measurements suggest the existence of two different quenching mechanisms: (1) a static quenching occurring below the lipid phase transition temperature, and (2) an additional dynamic quenching taking place in the fluid state of the lipid bilayer.", "contents": "Monitoring the location profile of fluorophores in phosphatidylcholine bilayers by the use or paramagnetic quenching. Spin probes differing in the position of their paramagnetic centre are used to quench the fluorescence of pyrene derivatives and chlorophylls incorporated into dimyristoyl phosphatidylcholine membranes. Pyrene butyric acid and pyrene decanoic acid with known orientation relative to the membrane surface are investigated. The quenching efficiency of fatty acid spin probes is dependent on the position of the nitroxide radical group in the fatty acid chain. Using this short range interaction we developed a spectroscopic method to chlorophyll-containing vesicles, we were able to characterize the orientation of the porphyrin ring within the membrane. Moreover, the chlorophyll fluorescence is also quenched by a water-soluble spin label. Therefore the porphyrin ring appears to be orientated in the polar head group region of the lipid layer, but not to be protruding out into the water phase. This conclusion is confirmed by the use of pyrene derivatives. Fluorescence quenching by a water-soluble spin label within the lipid matrix is observed even in the rigid state of the membrane. Fluorescence lifetime measurements suggest the existence of two different quenching mechanisms: (1) a static quenching occurring below the lipid phase transition temperature, and (2) an additional dynamic quenching taking place in the fluid state of the lipid bilayer."}
{"id": "PMID:221021", "title": "Mass isolation of cell surface membrane fragments from pigeon heart.", "content": "Cell surface membrane fragments were isolated and purified by successive rate zonal and isopycnic centrifugation of calcium oxalate-loaded pigeon heart microsomes in sucrose density gradients. The most highly purified cell membrane fraction sediments at a buoyant density of 1.105 g/ml. Some of the membrane pieces are present as open fragments and leaky vesicles, while others form tightly sealed vesicles of both inside-in and inside-out membrane orientation. The pigeon heart cell membrane preparation exhibits high (Na+ + K+ + Mg2+)-ATPase and adenylate cyclase activities. Additional activity of these enzymes is uncovered by sodium dodecyl sulfate and alamethicin, respectively. Electron microscopic inspection of the cell surface membrane preparation revealed (a) a predominance of thick-walled vesicles with smooth surfaces on negative staining and (b) binding of concanavalin A to the bulk of isolated membrane pieces following their incubation with the lectin.", "contents": "Mass isolation of cell surface membrane fragments from pigeon heart. Cell surface membrane fragments were isolated and purified by successive rate zonal and isopycnic centrifugation of calcium oxalate-loaded pigeon heart microsomes in sucrose density gradients. The most highly purified cell membrane fraction sediments at a buoyant density of 1.105 g/ml. Some of the membrane pieces are present as open fragments and leaky vesicles, while others form tightly sealed vesicles of both inside-in and inside-out membrane orientation. The pigeon heart cell membrane preparation exhibits high (Na+ + K+ + Mg2+)-ATPase and adenylate cyclase activities. Additional activity of these enzymes is uncovered by sodium dodecyl sulfate and alamethicin, respectively. Electron microscopic inspection of the cell surface membrane preparation revealed (a) a predominance of thick-walled vesicles with smooth surfaces on negative staining and (b) binding of concanavalin A to the bulk of isolated membrane pieces following their incubation with the lectin."}
{"id": "PMID:221022", "title": "Protein kinases of Dictyostelium discoideum, strain AX-2.", "content": "In cell homogenates of Dictyostelium discoideum, strain AX-2, four major soluble protein kinases (ATP:protein phosphotransferase, EC 2.7.1.37) and one membrane-associated protein kinase activity were identified. The enzymes showed high affinity for casein. One of the enzymes was purified by affinity chromatography on casein-coated Sepharose. The soluble high molecular weight enzymes phosphorylated histones, whereas the low molecular weight enzymes did not. The same protein kinase species were present in vegetative and aggregation-competent cells. Their specific activity, however, changed during the development to aggregation competence. None of the enzymes was stimulated by cyclic AMP or cyclic GMP, regardless of their origin from vegetative or aggregation-competent cells.", "contents": "Protein kinases of Dictyostelium discoideum, strain AX-2. In cell homogenates of Dictyostelium discoideum, strain AX-2, four major soluble protein kinases (ATP:protein phosphotransferase, EC 2.7.1.37) and one membrane-associated protein kinase activity were identified. The enzymes showed high affinity for casein. One of the enzymes was purified by affinity chromatography on casein-coated Sepharose. The soluble high molecular weight enzymes phosphorylated histones, whereas the low molecular weight enzymes did not. The same protein kinase species were present in vegetative and aggregation-competent cells. Their specific activity, however, changed during the development to aggregation competence. None of the enzymes was stimulated by cyclic AMP or cyclic GMP, regardless of their origin from vegetative or aggregation-competent cells."}
{"id": "PMID:221023", "title": "Cyclic AMP-dependent and -independent protein kinases of the water mold, Blastocladiella emersonii.", "content": "Protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37) and cyclic adenosine 3',5'-monophosphate binding activities have been identified in zoospore extracts of the water mold Blastocladiella emersonii. More than 75% of these activities is found in the soluble fraction. Soluble protein kinase activity is resolved in three peaks(I, II and III) by DEAE-cellulose chromatography. Peak I is casein dependent and insensitive to cyclic AMP. Peak II is histone dependent and cyclic AMP independent; this enzyme is inhibited by the heat-stable inhibitor from bovine muscle. Peak III utilizes histone as substrate and is activated by cyclic AMP.", "contents": "Cyclic AMP-dependent and -independent protein kinases of the water mold, Blastocladiella emersonii. Protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37) and cyclic adenosine 3',5'-monophosphate binding activities have been identified in zoospore extracts of the water mold Blastocladiella emersonii. More than 75% of these activities is found in the soluble fraction. Soluble protein kinase activity is resolved in three peaks(I, II and III) by DEAE-cellulose chromatography. Peak I is casein dependent and insensitive to cyclic AMP. Peak II is histone dependent and cyclic AMP independent; this enzyme is inhibited by the heat-stable inhibitor from bovine muscle. Peak III utilizes histone as substrate and is activated by cyclic AMP."}
{"id": "PMID:221024", "title": "Mode of action of bacterial collagenase on a synthetic substrate, (Pro-Pro-Gly)5.", "content": "Clostridial collagenase (EC 3.4.24.3) catalyzes the hydrolysis of (Pro-Pro-Gly)5 at minimum of three different rates, producing Pro-Pro, Gly-Pro-Pro and Gly-Pro-Pro-Gly, and various intermediate peptides. The intermediate and final products were separated by cation-exchange column chromatogrphy and identified, and their rates of formation were measured. Pro-Pro was released most rapidly with formation of the tridecapeptide. After the initial release of the N-terminal Pro-Pro, hexa- and heptapeptides were formed in larger amounts than tri-, tetra-, nona- and decapeptides from the tridecapeptide. The rates of disappearance of the intermediates decreased in the order trideca- greater than deca- and nona- greater than heptapeptide. The results indicate that the enzyme hydrolyzes inner linkages of the tridecapeptide having N- and C-terminal Gly residues, forming large peptides, preferentially to outer linkages, forming the tri- and tetrapeptides.", "contents": "Mode of action of bacterial collagenase on a synthetic substrate, (Pro-Pro-Gly)5. Clostridial collagenase (EC 3.4.24.3) catalyzes the hydrolysis of (Pro-Pro-Gly)5 at minimum of three different rates, producing Pro-Pro, Gly-Pro-Pro and Gly-Pro-Pro-Gly, and various intermediate peptides. The intermediate and final products were separated by cation-exchange column chromatogrphy and identified, and their rates of formation were measured. Pro-Pro was released most rapidly with formation of the tridecapeptide. After the initial release of the N-terminal Pro-Pro, hexa- and heptapeptides were formed in larger amounts than tri-, tetra-, nona- and decapeptides from the tridecapeptide. The rates of disappearance of the intermediates decreased in the order trideca- greater than deca- and nona- greater than heptapeptide. The results indicate that the enzyme hydrolyzes inner linkages of the tridecapeptide having N- and C-terminal Gly residues, forming large peptides, preferentially to outer linkages, forming the tri- and tetrapeptides."}
{"id": "PMID:221026", "title": "Purification and properties of the membrane-bound hydrogenase from Proteus mirabilis.", "content": "The cytoplasmic membrane-bound hydrogenase of the facultative anaerobe, Proteus mirabilis, has been solubilized and purified to homogeneity. The purified enzyme exhibited a maximal specific activity of about 780 mumol H2 oxidized/min per mg protein (benzyl viologen reduction). The hydrogenase has a molecular weight of 205 000 and is composed of two subunits with a molecular weight of 63 000 and two of 33 000. The absorption spectrum of the enzyme was characteristic of non-heme iron proteins. The millimolar extinction coefficients at 400 and 280 nm are 106 and 390, respectively. The hydrogenase has about 24 iron atoms and 24 acid-labile sulfide atoms/molecule. Amino acid analyses revealed the presence of 39 half-cystine residues/molecule and a preponderance of acidic amino acids. The hydrogenase in its oxidized form exhibits an EPR signal of the HiPIP-type with g values at 2.025 and 2.018. Upon reduction with either dithionite or H2 the signal disappears; no other signals were detectable.", "contents": "Purification and properties of the membrane-bound hydrogenase from Proteus mirabilis. The cytoplasmic membrane-bound hydrogenase of the facultative anaerobe, Proteus mirabilis, has been solubilized and purified to homogeneity. The purified enzyme exhibited a maximal specific activity of about 780 mumol H2 oxidized/min per mg protein (benzyl viologen reduction). The hydrogenase has a molecular weight of 205 000 and is composed of two subunits with a molecular weight of 63 000 and two of 33 000. The absorption spectrum of the enzyme was characteristic of non-heme iron proteins. The millimolar extinction coefficients at 400 and 280 nm are 106 and 390, respectively. The hydrogenase has about 24 iron atoms and 24 acid-labile sulfide atoms/molecule. Amino acid analyses revealed the presence of 39 half-cystine residues/molecule and a preponderance of acidic amino acids. The hydrogenase in its oxidized form exhibits an EPR signal of the HiPIP-type with g values at 2.025 and 2.018. Upon reduction with either dithionite or H2 the signal disappears; no other signals were detectable."}
{"id": "PMID:221027", "title": "The mechanism of electron transfer in laccase-catalysed reactions.", "content": "1. The reaction of the electron acceptors in Rhus vernicifera laccase (monophenol, dihydroxyphenylalanine:oxygen oxidoreductase, EC 1.14.18.1) have been studied with stopped-flow and rapid-freeze EPR techniques. The studies have been directed mainly towards elucidation of the role of the type 2Cu2+ as a possible pH-sensitve regulator of electron transfer. 2. Anaerobic reduction experiments with Rhus laccase indicate that the type 1 and 2 sites contribute one electron each to the reduction of the two-electron-accepting type 3 site. There is also evidence that the reduction of the type 1 Cu2+ triggers the reduction of the type 2 Cu2+. 3. Only at pH values at which the reduction of the two-electron acceptor is limited by a slow intramolecular reaction can an OH- be displaced from the type 2 Cu2+ by the inhibitor F-. 4. A model describing the role of the electron-accepting sites in catalysis is formulated.", "contents": "The mechanism of electron transfer in laccase-catalysed reactions. 1. The reaction of the electron acceptors in Rhus vernicifera laccase (monophenol, dihydroxyphenylalanine:oxygen oxidoreductase, EC 1.14.18.1) have been studied with stopped-flow and rapid-freeze EPR techniques. The studies have been directed mainly towards elucidation of the role of the type 2Cu2+ as a possible pH-sensitve regulator of electron transfer. 2. Anaerobic reduction experiments with Rhus laccase indicate that the type 1 and 2 sites contribute one electron each to the reduction of the two-electron-accepting type 3 site. There is also evidence that the reduction of the type 1 Cu2+ triggers the reduction of the type 2 Cu2+. 3. Only at pH values at which the reduction of the two-electron acceptor is limited by a slow intramolecular reaction can an OH- be displaced from the type 2 Cu2+ by the inhibitor F-. 4. A model describing the role of the electron-accepting sites in catalysis is formulated."}
{"id": "PMID:221028", "title": "The binding of spin-labeled derivatives of NAD+ and its structural components to pig skeletal muscle lactate dehydrogenase.", "content": "The binding of spin-labeled derivatives of NAD+ and its structural components to pig skeletal muscle lactate dehydrogenase (L-lactate:NAD+ oxidoreductase, EC 1.1.1.27) is described. In contrast to results previously obtained with the heart muscle isozyme (Wenzel, H.R., Pfleiderer, G., Trommer, W.E., Paschenda, K. and Redhardt, A. (1976) Biochim. Biophys. Acta 452,292--301), no significant increase is observed in the binding constant of N6-SL-ADP as compared N6-SL-AMP. This different behavior can be explained by the substitution of glutamine-31 for alanine in the muscle isozyme, which has been proposed to account for the the tighter binding of NADH to the heart type. In both isozymes the binding of the binding of the spin-labeled coenzyme itself is weaker than found for its structural components.", "contents": "The binding of spin-labeled derivatives of NAD+ and its structural components to pig skeletal muscle lactate dehydrogenase. The binding of spin-labeled derivatives of NAD+ and its structural components to pig skeletal muscle lactate dehydrogenase (L-lactate:NAD+ oxidoreductase, EC 1.1.1.27) is described. In contrast to results previously obtained with the heart muscle isozyme (Wenzel, H.R., Pfleiderer, G., Trommer, W.E., Paschenda, K. and Redhardt, A. (1976) Biochim. Biophys. Acta 452,292--301), no significant increase is observed in the binding constant of N6-SL-ADP as compared N6-SL-AMP. This different behavior can be explained by the substitution of glutamine-31 for alanine in the muscle isozyme, which has been proposed to account for the the tighter binding of NADH to the heart type. In both isozymes the binding of the binding of the spin-labeled coenzyme itself is weaker than found for its structural components."}
{"id": "PMID:221029", "title": "Isolation and characterization of yeast nicotinamide adenine dinucleotide kinase.", "content": "NAD+ kinase (ATP:NAD+ 2'-phosphotransferase, EC 2.7.1.23) from yeast has been purified utilizing ion-exchange and NAD+-agarose affinity chromatography to give a 2100-fold purification. The apparent homogeneity of the enzyme preparation was confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and analytical ultracentrifugation. The enzyme has a subunit molecular weight of 31,000, and a native molecular weight of 124,000, and is, thus, probably a tetramer. The single form of the enzyme has an apparent isoelectric point of 5.85. Initial velocity studies in the forward direction with both substrates gave intersecting Lineweaver-Burk plots, and this suggests a sequential mechanism in which both substrates are bound before products are released. Replots of these data were linear and gave Km values for NAD+ and ATP of 0.68 mM and 2.3 mM, respectively.", "contents": "Isolation and characterization of yeast nicotinamide adenine dinucleotide kinase. NAD+ kinase (ATP:NAD+ 2'-phosphotransferase, EC 2.7.1.23) from yeast has been purified utilizing ion-exchange and NAD+-agarose affinity chromatography to give a 2100-fold purification. The apparent homogeneity of the enzyme preparation was confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and analytical ultracentrifugation. The enzyme has a subunit molecular weight of 31,000, and a native molecular weight of 124,000, and is, thus, probably a tetramer. The single form of the enzyme has an apparent isoelectric point of 5.85. Initial velocity studies in the forward direction with both substrates gave intersecting Lineweaver-Burk plots, and this suggests a sequential mechanism in which both substrates are bound before products are released. Replots of these data were linear and gave Km values for NAD+ and ATP of 0.68 mM and 2.3 mM, respectively."}
{"id": "PMID:221030", "title": "Facilitation of ouabain binding to (Na+ + K+)-ATPase by vanadate at in vivo concentrations.", "content": "In the presence of Mg2+ vanadate was shown to facilitate ouabain binding to (Na+ + K+)-ATPase in much the same way as Pi does. Thus the hypothesis that vanadate interacts with the phosphate site of the enzyme seems to be supported by ouabain binding experiments. At given ouabain concentrations maximum binding is achieved at microM concentrations of vanadate whereas mM concentrations of Pi are needed. Na+ as well as K+ counteract ouabain binding but some cardiac glycoside binding is still possible at in vivo concentrations of these cations. A minor contamination of the enzyme preparations with vanadate could explain the in vitro binding of ouabain that can be obtained with Mg2+ and in the absence of Pi.", "contents": "Facilitation of ouabain binding to (Na+ + K+)-ATPase by vanadate at in vivo concentrations. In the presence of Mg2+ vanadate was shown to facilitate ouabain binding to (Na+ + K+)-ATPase in much the same way as Pi does. Thus the hypothesis that vanadate interacts with the phosphate site of the enzyme seems to be supported by ouabain binding experiments. At given ouabain concentrations maximum binding is achieved at microM concentrations of vanadate whereas mM concentrations of Pi are needed. Na+ as well as K+ counteract ouabain binding but some cardiac glycoside binding is still possible at in vivo concentrations of these cations. A minor contamination of the enzyme preparations with vanadate could explain the in vitro binding of ouabain that can be obtained with Mg2+ and in the absence of Pi."}
{"id": "PMID:221031", "title": "Validation of a procedure for exogenous isotopic labeling of lipoprotein triglyceride with radioactive triolein.", "content": "A procedure has been developed for the exogenous isotopic labeling of triglyceride-rich lipoproteins (chylomicrons and very low density lipoproteins) using high specific activity radioactive triglyceride in the presence of aqueous dimethyl sulfoxide. The labeled product lipoproteins showed unchanged chemical and physical properties. When the particles had also been labeled biologically by incorporation of unesterified fatty acids into the triglycerides of lipoproteins secreted by liver or intestine, both endogenous and exogenous labels were removed at the same rates in the isolated perfused heart and liver or in intact or functionally hepatectomized rats. These experiments additonally indicated that the triglyceride fatty acid composition of chylomicrons and very low density lipoproteins was unchanged during triglyceride depletion in the peripheral tissues. Using such labeled lipoproteins it has been shown that uptake of remnant lipoprotein cholesteryl ester and triglyceride by the liver is simultaneous. The labeling procedure described should prove suitable for kinetic studies of the disposition of the various lipoprotein non-polar ('core') lipids.", "contents": "Validation of a procedure for exogenous isotopic labeling of lipoprotein triglyceride with radioactive triolein. A procedure has been developed for the exogenous isotopic labeling of triglyceride-rich lipoproteins (chylomicrons and very low density lipoproteins) using high specific activity radioactive triglyceride in the presence of aqueous dimethyl sulfoxide. The labeled product lipoproteins showed unchanged chemical and physical properties. When the particles had also been labeled biologically by incorporation of unesterified fatty acids into the triglycerides of lipoproteins secreted by liver or intestine, both endogenous and exogenous labels were removed at the same rates in the isolated perfused heart and liver or in intact or functionally hepatectomized rats. These experiments additonally indicated that the triglyceride fatty acid composition of chylomicrons and very low density lipoproteins was unchanged during triglyceride depletion in the peripheral tissues. Using such labeled lipoproteins it has been shown that uptake of remnant lipoprotein cholesteryl ester and triglyceride by the liver is simultaneous. The labeling procedure described should prove suitable for kinetic studies of the disposition of the various lipoprotein non-polar ('core') lipids."}
{"id": "PMID:221032", "title": "Structure of membrane lipids and physico-biochemical properties of the plasma membrane from Thermoplasma acidophilum, adapted to growth at 37 degrees C.", "content": "Thermoplasma acidophilum, a mycoplasma-like organism, grows optimally at 56 degrees C and pH2. The low temperature extreme of growth is 37 degrees C. The plasma membrane of cells grown at 37 degrees C was isolated and characterized physicobiochemically. Membrane lipids which comprise 25% of the membrane dry weight consist mainly of two repetitively methyl-branched C40 side chains that were ether-linked to two glycerol molecules. The lipid structures were elucidated by combined gas chromatography-mass spectroscopy, direct probe mass spectroscopy and 13C NMR. 37 degrees C-grown cells contained lipids with 42% more pentane cyclization than the 56 degrees C-grown cells. In 37 degrees C-grown cells, phospholipid and serine content decreased by about 10% each, carbohydrate content increased by 5%. EPR studies demonstrated an increase in membrane lipid fluidity of 37 degrees C-grown cells with an upper transition temperature at 35 degrees C which was shifted down by 10 degrees C compared with cells grown at 56 degrees C. Membrane-bound ATPase activities also indicated similar changes upon adaptation. There is a close correlation between membrane fluidity and physiological functioning of this membrane-bound enzyme.", "contents": "Structure of membrane lipids and physico-biochemical properties of the plasma membrane from Thermoplasma acidophilum, adapted to growth at 37 degrees C. Thermoplasma acidophilum, a mycoplasma-like organism, grows optimally at 56 degrees C and pH2. The low temperature extreme of growth is 37 degrees C. The plasma membrane of cells grown at 37 degrees C was isolated and characterized physicobiochemically. Membrane lipids which comprise 25% of the membrane dry weight consist mainly of two repetitively methyl-branched C40 side chains that were ether-linked to two glycerol molecules. The lipid structures were elucidated by combined gas chromatography-mass spectroscopy, direct probe mass spectroscopy and 13C NMR. 37 degrees C-grown cells contained lipids with 42% more pentane cyclization than the 56 degrees C-grown cells. In 37 degrees C-grown cells, phospholipid and serine content decreased by about 10% each, carbohydrate content increased by 5%. EPR studies demonstrated an increase in membrane lipid fluidity of 37 degrees C-grown cells with an upper transition temperature at 35 degrees C which was shifted down by 10 degrees C compared with cells grown at 56 degrees C. Membrane-bound ATPase activities also indicated similar changes upon adaptation. There is a close correlation between membrane fluidity and physiological functioning of this membrane-bound enzyme."}
{"id": "PMID:221033", "title": "Transformation of 4-androsten-3,17-dione by growing cultures and cell extracts of Clostridium paraputrificum.", "content": "Growing cultures of Clostridium paraputrificum transformed 4-androsten-3,17-dione to 3 alpha-hydroxy-5 beta-androstan-17-one in a sequential manner with 5 beta-androstan-3,17-dione as an intermediate. The addition of 1.5 mM menadione to log-phase cultures which had formed 5 beta-androstan-3,17-dione resulted in a partial reoxidation of this steroid to 4-androsten-3,17-dione. However, this treatment also resulted in transient inhibition of culture growth. Resumption of growth was accompanied by complete reduction of 4-androsten-3,17-dione to 5 beta-androstan-3,17-dione. Cell extracts of C. paraputrificum were capable of carrying out these reductive transformations in the absence of added cofactors. However, Sephadex G-25 treated extracts required NADH or NADPH for these reactions. A flavin nucleotide, either FAD (plus NADH or NADPH) or FMN (plus NADH) was highly stimulatory for 4-androsten-3,17-dione reduction to 5 beta-androstan-3,17-dione. NADH was the preferred reduced pyridine nucleotide for reduction of the C4-C5 double bond, while time-course measurements suggested that NADPH was the preferred donor for reduction of the 3-keto group.", "contents": "Transformation of 4-androsten-3,17-dione by growing cultures and cell extracts of Clostridium paraputrificum. Growing cultures of Clostridium paraputrificum transformed 4-androsten-3,17-dione to 3 alpha-hydroxy-5 beta-androstan-17-one in a sequential manner with 5 beta-androstan-3,17-dione as an intermediate. The addition of 1.5 mM menadione to log-phase cultures which had formed 5 beta-androstan-3,17-dione resulted in a partial reoxidation of this steroid to 4-androsten-3,17-dione. However, this treatment also resulted in transient inhibition of culture growth. Resumption of growth was accompanied by complete reduction of 4-androsten-3,17-dione to 5 beta-androstan-3,17-dione. Cell extracts of C. paraputrificum were capable of carrying out these reductive transformations in the absence of added cofactors. However, Sephadex G-25 treated extracts required NADH or NADPH for these reactions. A flavin nucleotide, either FAD (plus NADH or NADPH) or FMN (plus NADH) was highly stimulatory for 4-androsten-3,17-dione reduction to 5 beta-androstan-3,17-dione. NADH was the preferred reduced pyridine nucleotide for reduction of the C4-C5 double bond, while time-course measurements suggested that NADPH was the preferred donor for reduction of the 3-keto group."}
{"id": "PMID:221034", "title": "Characterization of low density lipoprotein-like particle in the human aorta from grossly normal and atherosclerotic regions.", "content": "Physical and chemical criteria of lipoproteins containing apolipoprotein B, extracted from human aortic intima, were compared with those of plasma low density lipoproteins (LDL). Homogenates of grossly normal intima and advanced atherosclerotic lesions were subjected to differential ultracentrifugation to isolate a d = 1.006--1.063 g/ml density fraction which was extensively characterized. By electroimmunoassay, over 90% of the recovered apolipoprotein B immunological reactivity was found in isolates from both plaques and normal intima. In isolates of plaque and normal intima, particles of the same size as LDL were found, although a small population of very large structures was also present in plaque fractions. Apolipoprotein composition was similar to that of plasma LDL except for the presence of human serum albumin in aortic isolates. Fractions from aorta demonstrated greater electrophoretic mobilities than LDL. The lipid composition of isolates from normal intima was similar to that of LDL. The lipid composition of plaque fractions showed a significant decrease in the cholesteryl ester to free cholesterol ratio and in the triglyceride content in comparison to LDL and to fractions from normal intima. The fatty acid pattern of the cholesteryl ester fraction from isolates of both normal and plaque aortic homogenates demonstrated a significant decrease in the linoleate to oleate ratio as compared to LDL. Our initial studies suggest that althought aortic fractions are similar to LDL by certain criteria, some differences observed are more pronounced in fractions from lesions than from normal intima.", "contents": "Characterization of low density lipoprotein-like particle in the human aorta from grossly normal and atherosclerotic regions. Physical and chemical criteria of lipoproteins containing apolipoprotein B, extracted from human aortic intima, were compared with those of plasma low density lipoproteins (LDL). Homogenates of grossly normal intima and advanced atherosclerotic lesions were subjected to differential ultracentrifugation to isolate a d = 1.006--1.063 g/ml density fraction which was extensively characterized. By electroimmunoassay, over 90% of the recovered apolipoprotein B immunological reactivity was found in isolates from both plaques and normal intima. In isolates of plaque and normal intima, particles of the same size as LDL were found, although a small population of very large structures was also present in plaque fractions. Apolipoprotein composition was similar to that of plasma LDL except for the presence of human serum albumin in aortic isolates. Fractions from aorta demonstrated greater electrophoretic mobilities than LDL. The lipid composition of isolates from normal intima was similar to that of LDL. The lipid composition of plaque fractions showed a significant decrease in the cholesteryl ester to free cholesterol ratio and in the triglyceride content in comparison to LDL and to fractions from normal intima. The fatty acid pattern of the cholesteryl ester fraction from isolates of both normal and plaque aortic homogenates demonstrated a significant decrease in the linoleate to oleate ratio as compared to LDL. Our initial studies suggest that althought aortic fractions are similar to LDL by certain criteria, some differences observed are more pronounced in fractions from lesions than from normal intima."}
{"id": "PMID:221035", "title": "Structural organization of free and esterified cholesterol in human high density lipoproteins. A 100.6 MHz 13C NMR study.", "content": "The structural organization of free and esterified cholesterol in human high density lipoproteins has been studied by high-field 1H and 13C NMR. The measurements are consistent with free cholesterol being present in at least two different environments. Part of the free cholesterol is oriented in the outer surface layer of the high density lipoprotein particle in contact with phospholipid or apoprotein, or both. The rest is probably present in the liquid, hydrophobic core of the HDL particle.", "contents": "Structural organization of free and esterified cholesterol in human high density lipoproteins. A 100.6 MHz 13C NMR study. The structural organization of free and esterified cholesterol in human high density lipoproteins has been studied by high-field 1H and 13C NMR. The measurements are consistent with free cholesterol being present in at least two different environments. Part of the free cholesterol is oriented in the outer surface layer of the high density lipoprotein particle in contact with phospholipid or apoprotein, or both. The rest is probably present in the liquid, hydrophobic core of the HDL particle."}
{"id": "PMID:221036", "title": "In vivo transfer of cholesteryl esters from high density lipoproteins to very low density lipoproteins in man.", "content": "The fate of cholesteryl esters in high density lipoprotein (HDL) was studied to determine whether the transfer of esterified cholesterol from HDL to other plasma lipoproteins occurred to a significant extent in man. HDL cholesteryl ester, labelled in vitro with [3H] cholesterol, was injected into human subjects. Labelling of cholesteryl esters in very low density (VLDL) occurred rapidly and by 3 h, the esterified cholesterol in VLDL reached peak specific radioactivity. The removal rate of cholesteryl esters from HDL appeared to be exponential and of the order of 0.2/h; calculation of the apparent flux was about 150 mg/h which approximates reported values for total cholesterol esterification in human plasma in vivo. The rapid rate of labelling of VLDL from HDL suggests that the transfer of HDL cholesteryl esters to VLDL may represent a significant pathway for the disposal of HDL cholesterol.", "contents": "In vivo transfer of cholesteryl esters from high density lipoproteins to very low density lipoproteins in man. The fate of cholesteryl esters in high density lipoprotein (HDL) was studied to determine whether the transfer of esterified cholesterol from HDL to other plasma lipoproteins occurred to a significant extent in man. HDL cholesteryl ester, labelled in vitro with [3H] cholesterol, was injected into human subjects. Labelling of cholesteryl esters in very low density (VLDL) occurred rapidly and by 3 h, the esterified cholesterol in VLDL reached peak specific radioactivity. The removal rate of cholesteryl esters from HDL appeared to be exponential and of the order of 0.2/h; calculation of the apparent flux was about 150 mg/h which approximates reported values for total cholesterol esterification in human plasma in vivo. The rapid rate of labelling of VLDL from HDL suggests that the transfer of HDL cholesteryl esters to VLDL may represent a significant pathway for the disposal of HDL cholesterol."}
{"id": "PMID:221037", "title": "Different developmental changes in latency for two functions of a single membrane bound enzyme: glucose-6-phosphatase activities as a function of age.", "content": "(1). The capacity for the synthesis of glucose 6-phosphate from PPi and glucose as well as for glucose-6-P hydrolysis, catalyzed by rat liver microsomal glucose-6-phosphatase, increases rapidly from low prenatal levels to a maximum between the second and fifth day, then slowly decreases to reach adult levels. When measured in enzyme preparations optimally activated by hydroxyl ions, the maximum neonatal activities were 4--5-fold higher than in adult animals and several-fold higher than had previously been observed for the unactivated enzyme. (2) The latencies of two catalytic activities associated with the same membrane-bound enzyme show strikingly different age-related changes. The latency of PPi-glucose phosphotransferase activity reaches high levels (60--80% latent) soon after birth and remains high throughout life, while the latency of glucose-6-P phosphohydrolase decreases with age. The phosphohydrolase is 2--3 times more latent in the liver of the neonatal animal than in the adult. (3). The well established neonatal overshoot of liver glucose-6-phosphatase is almost entirely due to changes in the enzyme in the rough microsomal membranes. The enzyme activity in the rough membrane reaches a maximum and then decreases after day 2, while that in the smooth membrane is still slowly increasing. Despite the great differences in absolute specific activities and in the pattern of early enzyme development between the rough and smooth microsomes, enzyme latency in the two subfractions remains parallel, glucose-6-P phosphohydrolase being only slightly more latent, while PPi-glucose phospho-transferase is much more latent in smooth than in rough membranes throughout life. (4). Kidney glucose-6-P phosphohydrolase and PPi-glucose phosphotransferase activities were found to change in a parallel fashion with age, showing a small neonatal peak between days 2 and 7 before rising to adult levels. Kidney phosphotransferase activity, like that of liver, remained highly latent throughout life. In contrast to liver, the glucose-6-P phosphohydrolase of kidney did not show a characteristic decrease in latency with age and in the adult remained appreciably more latent than in liver. (5). An improved method was devised for the separation of smooth microsomes from liver homogenates.", "contents": "Different developmental changes in latency for two functions of a single membrane bound enzyme: glucose-6-phosphatase activities as a function of age. (1). The capacity for the synthesis of glucose 6-phosphate from PPi and glucose as well as for glucose-6-P hydrolysis, catalyzed by rat liver microsomal glucose-6-phosphatase, increases rapidly from low prenatal levels to a maximum between the second and fifth day, then slowly decreases to reach adult levels. When measured in enzyme preparations optimally activated by hydroxyl ions, the maximum neonatal activities were 4--5-fold higher than in adult animals and several-fold higher than had previously been observed for the unactivated enzyme. (2) The latencies of two catalytic activities associated with the same membrane-bound enzyme show strikingly different age-related changes. The latency of PPi-glucose phosphotransferase activity reaches high levels (60--80% latent) soon after birth and remains high throughout life, while the latency of glucose-6-P phosphohydrolase decreases with age. The phosphohydrolase is 2--3 times more latent in the liver of the neonatal animal than in the adult. (3). The well established neonatal overshoot of liver glucose-6-phosphatase is almost entirely due to changes in the enzyme in the rough microsomal membranes. The enzyme activity in the rough membrane reaches a maximum and then decreases after day 2, while that in the smooth membrane is still slowly increasing. Despite the great differences in absolute specific activities and in the pattern of early enzyme development between the rough and smooth microsomes, enzyme latency in the two subfractions remains parallel, glucose-6-P phosphohydrolase being only slightly more latent, while PPi-glucose phospho-transferase is much more latent in smooth than in rough membranes throughout life. (4). Kidney glucose-6-P phosphohydrolase and PPi-glucose phosphotransferase activities were found to change in a parallel fashion with age, showing a small neonatal peak between days 2 and 7 before rising to adult levels. Kidney phosphotransferase activity, like that of liver, remained highly latent throughout life. In contrast to liver, the glucose-6-P phosphohydrolase of kidney did not show a characteristic decrease in latency with age and in the adult remained appreciably more latent than in liver. (5). An improved method was devised for the separation of smooth microsomes from liver homogenates."}
{"id": "PMID:221038", "title": "Inhibition of K+-sensitive p-nitrophenylphosphatase activity on Rhesus-positive red cells after incubation with IgG-anti-Rhesus-D.", "content": "The incubation of ghosts derived from human Rhesus-positive red cells with IgG-anti-Rhesus-D inhibited the K+-sensitive p-nitrophenylphosphatase activity. This enzyme has a partial function in the (Na+ + K+)-ATPase system related to the phosphorylation step, which is important for active potassium transport through the red cell membrane. The specificity of the impairment by the antigen-antibody reaction in the Rhesus-D system was proved by the following controls. Ghosts obtained from Rhesus-negative red cells incubated by IgG-anti-Rhesus-D and those of Rhesus-positive red cells treated with non-immune serum did not show any reduction of the K+-p-nitrophenylphosphatase activity. The ghost preparation with lanthanum carried out after hypotonic hemolysis of the washed red cells in 2 mM LaCl3 at pH 6 was the most suitable procedure to explore this topic in comparison to other techniques for preparing ghosts of red cells.", "contents": "Inhibition of K+-sensitive p-nitrophenylphosphatase activity on Rhesus-positive red cells after incubation with IgG-anti-Rhesus-D. The incubation of ghosts derived from human Rhesus-positive red cells with IgG-anti-Rhesus-D inhibited the K+-sensitive p-nitrophenylphosphatase activity. This enzyme has a partial function in the (Na+ + K+)-ATPase system related to the phosphorylation step, which is important for active potassium transport through the red cell membrane. The specificity of the impairment by the antigen-antibody reaction in the Rhesus-D system was proved by the following controls. Ghosts obtained from Rhesus-negative red cells incubated by IgG-anti-Rhesus-D and those of Rhesus-positive red cells treated with non-immune serum did not show any reduction of the K+-p-nitrophenylphosphatase activity. The ghost preparation with lanthanum carried out after hypotonic hemolysis of the washed red cells in 2 mM LaCl3 at pH 6 was the most suitable procedure to explore this topic in comparison to other techniques for preparing ghosts of red cells."}
{"id": "PMID:221039", "title": "Protein phosphorylation in rat caudate homogenate: stimulatory effects of dopamine and enhancement of dopamine response following 6-hydroxydopamine treatment.", "content": "Dopamine (3-hydroxytyramine) stimulates the incorporation of 32P into proteins endogenous to a homogenate of rat caudate nucleus when 10 microM [gamma-32P]-ATP is used as a substrate following preincubation with 400 microM ATP. The increase in 32P incorporation has pharmacological characteristics similar to caudate tissue. Chronic depletion of striatal dopamine in vivo by stereotaxic injection of 6-hydroxydopamine in the nigrostriatal pathway results in a significant enhancement of the dopamine stimulation of 32 p incorporation in vitro. Cyclic AMP-stimulated phosphorylation of caudate proteins remains unchanged following 6-hydroxydopamine treatment.", "contents": "Protein phosphorylation in rat caudate homogenate: stimulatory effects of dopamine and enhancement of dopamine response following 6-hydroxydopamine treatment. Dopamine (3-hydroxytyramine) stimulates the incorporation of 32P into proteins endogenous to a homogenate of rat caudate nucleus when 10 microM [gamma-32P]-ATP is used as a substrate following preincubation with 400 microM ATP. The increase in 32P incorporation has pharmacological characteristics similar to caudate tissue. Chronic depletion of striatal dopamine in vivo by stereotaxic injection of 6-hydroxydopamine in the nigrostriatal pathway results in a significant enhancement of the dopamine stimulation of 32 p incorporation in vitro. Cyclic AMP-stimulated phosphorylation of caudate proteins remains unchanged following 6-hydroxydopamine treatment."}
{"id": "PMID:221040", "title": "Change of isozyme pattern during activation of a transforming gene product: its relation to other biochemical markers of cellular transformation and differentiation.", "content": "Isozyme patterns of leucine aminotransferase were studied in connection with glucose transport and DNA synthesis during the activation and deactivation of the transforming gene product in rat kidney cells transformed by one Rous sarcoma virus mutant (which has a temperature-sensitive lesion in its transforming gene. On temperature shift-down of confluent transformed cells grown at 40 degrees C in the presence of fresh serum, isozyme III of leucine aminotransferase appeared in 12--20 h, with increasing amounts from 24 to 48 h. Upon temperature shift-up, isozyme I became the predominant form in these cells within 4 days, the major change occurring within the first 24 h. The rate of protein turnover was similar to the rate of loss of isozymes I and III during temperature shift-down and shift-up, respectively. A stimulation of incorporation of [3H]thymidine into DNA was observed within 8--12 h after temperature shift-down of the transformed cells. For the maintenance of stimulated DNA synthesis for at least 16 h, continued exposure to the permissive temperature is not necessary. Stimulation of glucose transport occurred prior to the stimulation of [3H]thymidine incorporation. The isozymes of leucine aminotransferase also changed during the in vitro differentiation of Yaffee L6A cells in such a way that isozyme I represented the major part of this enzyme in the fused myotube, and isozyme III was more predominant in the less differentiated state (mononucleated cells).", "contents": "Change of isozyme pattern during activation of a transforming gene product: its relation to other biochemical markers of cellular transformation and differentiation. Isozyme patterns of leucine aminotransferase were studied in connection with glucose transport and DNA synthesis during the activation and deactivation of the transforming gene product in rat kidney cells transformed by one Rous sarcoma virus mutant (which has a temperature-sensitive lesion in its transforming gene. On temperature shift-down of confluent transformed cells grown at 40 degrees C in the presence of fresh serum, isozyme III of leucine aminotransferase appeared in 12--20 h, with increasing amounts from 24 to 48 h. Upon temperature shift-up, isozyme I became the predominant form in these cells within 4 days, the major change occurring within the first 24 h. The rate of protein turnover was similar to the rate of loss of isozymes I and III during temperature shift-down and shift-up, respectively. A stimulation of incorporation of [3H]thymidine into DNA was observed within 8--12 h after temperature shift-down of the transformed cells. For the maintenance of stimulated DNA synthesis for at least 16 h, continued exposure to the permissive temperature is not necessary. Stimulation of glucose transport occurred prior to the stimulation of [3H]thymidine incorporation. The isozymes of leucine aminotransferase also changed during the in vitro differentiation of Yaffee L6A cells in such a way that isozyme I represented the major part of this enzyme in the fused myotube, and isozyme III was more predominant in the less differentiated state (mononucleated cells)."}
{"id": "PMID:221042", "title": "A heat-stable protein inhibitor of cyclic 3',5'-nucleotide phosphodiesterase.", "content": "A heat-stable, non-dialyzable inhibitory factor of cyclic nucleotide phosphodieterase was detected in and partially purified from bovine retina. The factor appears to be a protein, since the inhibitory activity was abolished by trypsin digestion but not by DNAase or RNAase treatment. The protein inhibitor from bovine retina effectively inhibits the Ca2+-independent phosphodiesterase from several sources, including bovine retina, bovine rod outer segment, and a human lymphoblastic leukemia cell line, indicating lack of tissue and species specificity.", "contents": "A heat-stable protein inhibitor of cyclic 3',5'-nucleotide phosphodiesterase. A heat-stable, non-dialyzable inhibitory factor of cyclic nucleotide phosphodieterase was detected in and partially purified from bovine retina. The factor appears to be a protein, since the inhibitory activity was abolished by trypsin digestion but not by DNAase or RNAase treatment. The protein inhibitor from bovine retina effectively inhibits the Ca2+-independent phosphodiesterase from several sources, including bovine retina, bovine rod outer segment, and a human lymphoblastic leukemia cell line, indicating lack of tissue and species specificity."}
{"id": "PMID:221043", "title": "Amylase release from rat parotid glands. I. General characteristics.", "content": "The involvement of calcium, ATP, and cyclic AMP-dependent protein kinase activity in the release of amylase from rat parotid glands was examined. Pretreatment of the glandular tissue in 11.25 mM Ca2+ medium potentiated the secretory responses to: dibutyryl cyclic AMP, elevation of the extracellular K+ concentration, reduction of the H+ concentration, La3+, and caffeine. Uncoupling of oxidative phosphorylation blocked release induced by dibutyryl cyclic AMP, K+, and reduction of H+, but had no effect on La3+, caffeine or tolbutamide-stimulated release. Inhibition of cyclic AMP-dependent protein kinase activity blocked only dibutyryl cyclic AMP-induced release and did not inhibit the responses to K+, reduction of H+ or caffeine. The loss of lactate dehydrogenase was used to access the integrity of the tissue during amylase release. No significant increase in the release of lactate dehydrogenase was observed during the secretory responses to: dibutyryl cyclic AMP, La3+, caffeine, or tolbutamide. Triton X-100 and ethanol increased the efflux of both amylase and lactate dehydrogenase. The differential involvement of Ca2+, ATP, and cyclic AMP-dependent protein kinase activity in amylase release induced by the various secretagogues suggests that three types of reactions are involved in the release of amylase.", "contents": "Amylase release from rat parotid glands. I. General characteristics. The involvement of calcium, ATP, and cyclic AMP-dependent protein kinase activity in the release of amylase from rat parotid glands was examined. Pretreatment of the glandular tissue in 11.25 mM Ca2+ medium potentiated the secretory responses to: dibutyryl cyclic AMP, elevation of the extracellular K+ concentration, reduction of the H+ concentration, La3+, and caffeine. Uncoupling of oxidative phosphorylation blocked release induced by dibutyryl cyclic AMP, K+, and reduction of H+, but had no effect on La3+, caffeine or tolbutamide-stimulated release. Inhibition of cyclic AMP-dependent protein kinase activity blocked only dibutyryl cyclic AMP-induced release and did not inhibit the responses to K+, reduction of H+ or caffeine. The loss of lactate dehydrogenase was used to access the integrity of the tissue during amylase release. No significant increase in the release of lactate dehydrogenase was observed during the secretory responses to: dibutyryl cyclic AMP, La3+, caffeine, or tolbutamide. Triton X-100 and ethanol increased the efflux of both amylase and lactate dehydrogenase. The differential involvement of Ca2+, ATP, and cyclic AMP-dependent protein kinase activity in amylase release induced by the various secretagogues suggests that three types of reactions are involved in the release of amylase."}
{"id": "PMID:221044", "title": "A Leydig cell tumour: a model for the study of lutropin action.", "content": "The properties of cells isolated from a Leydig cell tumour have been compared with normal rat testis Leydig cells. These cells were found to be similar in the following respects: 1. Lutropin-stimulated cyclic AMP and testosterone production. 2. Lutropin-activated protein kinase activity followed by phosphorylation of endogenous proteins of mol. wts. 57,000and 14,000. 3. Parallel lutropin dose vs. response curves for phosphorylation of the endogenous proteins and for testosterone production. 4. Two forms of isoenzyme, cyclic AMP dependent protein kinase, present. They differed mainly with respect to the lutropin-stimulated testosterone production, which was much lower in the tumour cells compared with the normal adult testis Leydig cells (4.6 +/- 1.1 and 114 +/- 16 ng testosterone/10(6) cells per 2 h, respectively). However, the lutropin-stimulated steroid production in the tumour cells was quantitatively comparable with the normal rat Leydig cell when the metabolism of pregnenolone in intact cells and mitochondria was inhibited by addition of SU-10603 and/or cyanoketone. It is concluded that the Leydig cell tumour used in this study can be used to investigate certain aspects of lutropin action where large quantities of cells are required.", "contents": "A Leydig cell tumour: a model for the study of lutropin action. The properties of cells isolated from a Leydig cell tumour have been compared with normal rat testis Leydig cells. These cells were found to be similar in the following respects: 1. Lutropin-stimulated cyclic AMP and testosterone production. 2. Lutropin-activated protein kinase activity followed by phosphorylation of endogenous proteins of mol. wts. 57,000and 14,000. 3. Parallel lutropin dose vs. response curves for phosphorylation of the endogenous proteins and for testosterone production. 4. Two forms of isoenzyme, cyclic AMP dependent protein kinase, present. They differed mainly with respect to the lutropin-stimulated testosterone production, which was much lower in the tumour cells compared with the normal adult testis Leydig cells (4.6 +/- 1.1 and 114 +/- 16 ng testosterone/10(6) cells per 2 h, respectively). However, the lutropin-stimulated steroid production in the tumour cells was quantitatively comparable with the normal rat Leydig cell when the metabolism of pregnenolone in intact cells and mitochondria was inhibited by addition of SU-10603 and/or cyanoketone. It is concluded that the Leydig cell tumour used in this study can be used to investigate certain aspects of lutropin action where large quantities of cells are required."}
{"id": "PMID:221046", "title": "Role of cytoskeletal elements in cytochalasin E-induced superoxide production by human polymorphonuclear leukocytes.", "content": "The release of superoxide anions from human polymorphonuclear leukocytes induced by cytochalasin E was greatly enhanced by the pretreatment of the cells either with deuterium oxide or with concanavalin A. Colchicine, vinblastine and cyclic AMP inhibited the release. Cytochalasins A and B also suppressed the superoxide release. These observations suggest the involvement of microfilament-microtubule system in the production and release of superoxide anions induced by cytochalasin E.", "contents": "Role of cytoskeletal elements in cytochalasin E-induced superoxide production by human polymorphonuclear leukocytes. The release of superoxide anions from human polymorphonuclear leukocytes induced by cytochalasin E was greatly enhanced by the pretreatment of the cells either with deuterium oxide or with concanavalin A. Colchicine, vinblastine and cyclic AMP inhibited the release. Cytochalasins A and B also suppressed the superoxide release. These observations suggest the involvement of microfilament-microtubule system in the production and release of superoxide anions induced by cytochalasin E."}
{"id": "PMID:221047", "title": "Comparison of cyclic nucleotide specificity of guanosine 3',5'-monophosphate-dependent protein kinase and adenosine 3',5'-monophosphate-dependent protein kinase.", "content": "Guanosine 3',5'-monophosphate-dependent protein kinase (cyclic GMP-dependent protein kinase) and adenosine 3',5'-monophosphate-dependent protein kinase (cyclic AMP-dependent protein kinase) exhibited a high degree of cyclic nucleotide specificity when hormone-sensitive triacylglycerol lipase, phosphorylase kinase, and cardiac troponin were used as substrates. The concentration of cyclic GMP required to activate half-maximally cyclic dependent protein kinase was 1000- to 100-fold less than that of cyclic AMP with these substrates. The opposite was true with cyclic AMP-dependent protein kinase where 1000- to 100-fold less cyclic AMP than cyclic GMP was required for half-maximal enzyme activation. This contrasts with the lower degree of cyclic nucleotide specificity of cyclic GMP-dependent protein kinase of 25-fold when histone H2b was used as a substrate for phosphorylation. Cyclic IMP resembled cyclic AMP in effectiveness in stimulating cyclic GMP-dependent protein kinase but was intermediate between cyclic AMP and cyclic GMP in stimulating cyclic AMP-dependent protein kinase. The effect of cyclic IMP on cyclic GMP-dependent protein kinase was confirmed in studies of autophosphorylation of cyclic GMP-dependent protein kinase where both cyclic AMP and cyclic IMP enhanced autophosphorylation. The high degree of cyclic nucleotide specificity observed suggests that cyclic AMP and cyclic GMP activate only their specific kinase and that crossover to the opposite kinase is unlikely to occur at reported cellular concentrations of cyclic nucleotides.", "contents": "Comparison of cyclic nucleotide specificity of guanosine 3',5'-monophosphate-dependent protein kinase and adenosine 3',5'-monophosphate-dependent protein kinase. Guanosine 3',5'-monophosphate-dependent protein kinase (cyclic GMP-dependent protein kinase) and adenosine 3',5'-monophosphate-dependent protein kinase (cyclic AMP-dependent protein kinase) exhibited a high degree of cyclic nucleotide specificity when hormone-sensitive triacylglycerol lipase, phosphorylase kinase, and cardiac troponin were used as substrates. The concentration of cyclic GMP required to activate half-maximally cyclic dependent protein kinase was 1000- to 100-fold less than that of cyclic AMP with these substrates. The opposite was true with cyclic AMP-dependent protein kinase where 1000- to 100-fold less cyclic AMP than cyclic GMP was required for half-maximal enzyme activation. This contrasts with the lower degree of cyclic nucleotide specificity of cyclic GMP-dependent protein kinase of 25-fold when histone H2b was used as a substrate for phosphorylation. Cyclic IMP resembled cyclic AMP in effectiveness in stimulating cyclic GMP-dependent protein kinase but was intermediate between cyclic AMP and cyclic GMP in stimulating cyclic AMP-dependent protein kinase. The effect of cyclic IMP on cyclic GMP-dependent protein kinase was confirmed in studies of autophosphorylation of cyclic GMP-dependent protein kinase where both cyclic AMP and cyclic IMP enhanced autophosphorylation. The high degree of cyclic nucleotide specificity observed suggests that cyclic AMP and cyclic GMP activate only their specific kinase and that crossover to the opposite kinase is unlikely to occur at reported cellular concentrations of cyclic nucleotides."}
{"id": "PMID:221048", "title": "Rat pancreas adenylate cyclase. VI. Role of the enzyme in secretin stimulated enzyme secretion.", "content": "1. The responsiveness of adenylate cyclase and enzyme secretin for secretin and the C-terminal octapeptide of pancreozymin has been investigated in particulate fractions of the pancreas of five different species. 2. The adenylate cyclase is sensitive to the C-terminal octapeptide of pancreozymin in all species investigated. 3. The enzyme is much more sensitive to secretin in rat and cat than in mouse and rabbit, whereas with guinea pig intermediate values are obtained. 4. The enzyme secretion is stimulated by secretin in pancreatic fragments of rat and cat, but not in those of mouse and rabbit. 5. These results suggest that in species where secretin stimulated enzyme secretion, it does so by stimulating the adenylate cyclase system.", "contents": "Rat pancreas adenylate cyclase. VI. Role of the enzyme in secretin stimulated enzyme secretion. 1. The responsiveness of adenylate cyclase and enzyme secretin for secretin and the C-terminal octapeptide of pancreozymin has been investigated in particulate fractions of the pancreas of five different species. 2. The adenylate cyclase is sensitive to the C-terminal octapeptide of pancreozymin in all species investigated. 3. The enzyme is much more sensitive to secretin in rat and cat than in mouse and rabbit, whereas with guinea pig intermediate values are obtained. 4. The enzyme secretion is stimulated by secretin in pancreatic fragments of rat and cat, but not in those of mouse and rabbit. 5. These results suggest that in species where secretin stimulated enzyme secretion, it does so by stimulating the adenylate cyclase system."}
{"id": "PMID:221049", "title": "Transferrin receptors during rabbit reticulocyte maturation.", "content": "Experiments were performed to examine the fate of transferrin receptors in reticulocytes as these cells mature in vivo to erythrocytes. Reticulocytosis, synchronized by administration of actinomycin D, was induced in adult rabbits. Simultaneous measurements were made of haematological parameters and the interaction between transferrin and reticulocytes while the cells matured in vivo to erythrocytes. As the reticulocytes matured there was a parallel decline in their ability to take up transferrin and transferrin iron. At the same time, there was a proportionate decrease in the density of receptors for transferrin on the reticulocyte surface. The affinity of the receptors for transferrin remained unaltered during the maturation process. It was concluded that the inability of erythrocytes to take up transferrin or its iron is due primarily to the loss of transferrin receptors from the maturing reticulocyte surface.", "contents": "Transferrin receptors during rabbit reticulocyte maturation. Experiments were performed to examine the fate of transferrin receptors in reticulocytes as these cells mature in vivo to erythrocytes. Reticulocytosis, synchronized by administration of actinomycin D, was induced in adult rabbits. Simultaneous measurements were made of haematological parameters and the interaction between transferrin and reticulocytes while the cells matured in vivo to erythrocytes. As the reticulocytes matured there was a parallel decline in their ability to take up transferrin and transferrin iron. At the same time, there was a proportionate decrease in the density of receptors for transferrin on the reticulocyte surface. The affinity of the receptors for transferrin remained unaltered during the maturation process. It was concluded that the inability of erythrocytes to take up transferrin or its iron is due primarily to the loss of transferrin receptors from the maturing reticulocyte surface."}
{"id": "PMID:221050", "title": "Stimulation by polyamines of carbamylphosphate:glucose phosphotransferase and glucose-6-phosphate phosphohydrolase activities of multifunctional glucose-6-phosphatase.", "content": "The effects of added polyamines on carbamylphosphate (carbamyl-P):glucose phosphotransferase and glucose-6-phosphate (Glc-6-P) phosphohydrolase activities of rat hepatic D-Glc-6-P phosphohydrolase (EC 3.1.3.9) of intact and detergent-treated microsomes have been investigated. With the former preparation, in the presence of 1.4 mM phosphate substrate and 90 mM D-glucose (phosphotransferase), 1 mM spermine, spermidine, and putrescine activated Glc-6-P phosphohydrolase 67%, 57%, and 35%, respectively. Carbamyl-P:glucose phosphotransferase, under comparable conditions, was activated 57%, 34%, and 18%. NH+4 (0.25--5.0 mM) produced at best but a minor activation (0--14%), while poly(L-lysine) (Mr = 3400; degree of polymerization 16) equimolar relative to other polyamines with respect to ionized free amino groups activated the hydrolase 358% and the transferase 222%. Treatment of microsomes with the detergent deoxycholate reduced, but did not abolish, polyamine-induced activation. The stimulatory effects of polyamines persisted in the presence of excess catalase, indicating their independence from H2O2 formation; and were eliminated in the presence of Ca2+. Kinetic analysis revealed that all tested polyamines decreased the apparent Michaelis constant values for carbamyl-P and Glc-6-P, but had no effect on the Km for glucose. Poly(L-lysine) increased the V value for both Glc-6-P phosphohydrolase and apparent V values for phosphotransferase extrapolated to infinite concentrations of either carbamyl-P or glucose. The other tested polyamines elevated only this last velocity parameter. It is proposed that a major mechanism by which polyamines activate glucose-6-phosphatase-phosphotransferase is through their electrostatic interactions with phospholipids of the membrane of the endoplasmic reticulum of which this enzyme is a part. Conformational alterations thus induced may in turn affect catalytic behavior. It is suggested that polyamines, or similar positively charged peptides, might participate in the cellular regulation of synthetic and hydrolytic activities of glucose-6-phosphatase.", "contents": "Stimulation by polyamines of carbamylphosphate:glucose phosphotransferase and glucose-6-phosphate phosphohydrolase activities of multifunctional glucose-6-phosphatase. The effects of added polyamines on carbamylphosphate (carbamyl-P):glucose phosphotransferase and glucose-6-phosphate (Glc-6-P) phosphohydrolase activities of rat hepatic D-Glc-6-P phosphohydrolase (EC 3.1.3.9) of intact and detergent-treated microsomes have been investigated. With the former preparation, in the presence of 1.4 mM phosphate substrate and 90 mM D-glucose (phosphotransferase), 1 mM spermine, spermidine, and putrescine activated Glc-6-P phosphohydrolase 67%, 57%, and 35%, respectively. Carbamyl-P:glucose phosphotransferase, under comparable conditions, was activated 57%, 34%, and 18%. NH+4 (0.25--5.0 mM) produced at best but a minor activation (0--14%), while poly(L-lysine) (Mr = 3400; degree of polymerization 16) equimolar relative to other polyamines with respect to ionized free amino groups activated the hydrolase 358% and the transferase 222%. Treatment of microsomes with the detergent deoxycholate reduced, but did not abolish, polyamine-induced activation. The stimulatory effects of polyamines persisted in the presence of excess catalase, indicating their independence from H2O2 formation; and were eliminated in the presence of Ca2+. Kinetic analysis revealed that all tested polyamines decreased the apparent Michaelis constant values for carbamyl-P and Glc-6-P, but had no effect on the Km for glucose. Poly(L-lysine) increased the V value for both Glc-6-P phosphohydrolase and apparent V values for phosphotransferase extrapolated to infinite concentrations of either carbamyl-P or glucose. The other tested polyamines elevated only this last velocity parameter. It is proposed that a major mechanism by which polyamines activate glucose-6-phosphatase-phosphotransferase is through their electrostatic interactions with phospholipids of the membrane of the endoplasmic reticulum of which this enzyme is a part. Conformational alterations thus induced may in turn affect catalytic behavior. It is suggested that polyamines, or similar positively charged peptides, might participate in the cellular regulation of synthetic and hydrolytic activities of glucose-6-phosphatase."}
{"id": "PMID:221056", "title": "Chromosome aberrations in B lymphocytes of atomic bomb survivors.", "content": "Although chromosome aberrations in T lymphocytes and bone marrow cells have been reported in atomic bomb survivors, the presence of chromosome abnormalities has not been demonstrated in B lymphocytes because of the technical difficulties involved in B-lymphocyte separation. A method for detecting chromosome aberrations in B lymphocytes was established by \"stimulation\" of B lymphocytes with Epstein-Barr virus (EBV) instead of \"separation\" of B lymphocytes by rosette formation. The EBV-stimulated lymphocytes were isolated as single colonies in soft agar and transferred to liquid culture for further cell growth. The EBV-stimulated B lymphocytes of two heavily exposed survivors showed 50% and 12.5% chromosome abnormalities 30 yr after exposure to the effects of the atomic bomb. The former patient seemed to have a karyotypically abnormal clone of B lymphocytes in vivo. The method used in this study and the evidence of chromosome aberrations in B lymphocytes for long periods after radiation exposure will be useful and important in elucidating the malignant processes of acute lymphocytic leukemia, B-cell lymphoma, and multiple myeloma among high-risk groups having a history of accidental or therapeutic exposure to radiation or radiomimetic drugs.", "contents": "Chromosome aberrations in B lymphocytes of atomic bomb survivors. Although chromosome aberrations in T lymphocytes and bone marrow cells have been reported in atomic bomb survivors, the presence of chromosome abnormalities has not been demonstrated in B lymphocytes because of the technical difficulties involved in B-lymphocyte separation. A method for detecting chromosome aberrations in B lymphocytes was established by \"stimulation\" of B lymphocytes with Epstein-Barr virus (EBV) instead of \"separation\" of B lymphocytes by rosette formation. The EBV-stimulated lymphocytes were isolated as single colonies in soft agar and transferred to liquid culture for further cell growth. The EBV-stimulated B lymphocytes of two heavily exposed survivors showed 50% and 12.5% chromosome abnormalities 30 yr after exposure to the effects of the atomic bomb. The former patient seemed to have a karyotypically abnormal clone of B lymphocytes in vivo. The method used in this study and the evidence of chromosome aberrations in B lymphocytes for long periods after radiation exposure will be useful and important in elucidating the malignant processes of acute lymphocytic leukemia, B-cell lymphoma, and multiple myeloma among high-risk groups having a history of accidental or therapeutic exposure to radiation or radiomimetic drugs."}
{"id": "PMID:221052", "title": "[Free radicals formed during UV-irradiation of unsaturated fatty acids containing peroxidation products].", "content": "On the irradiation of oxidized linolic acid an assymetric ESR signal with g-factor 2.0039 and the linewidth 30--33 Oe has been registered. The signal could be the result of photolysis of hydroperoxides. During prolonged irradiation of all the samples accumulation of alkyl radicals characterized by a symmetric signal with a well-defined ultrafine structure has been observed. An increase of the sample temperature up to 87 K in the presence of oxygen was preceded by transformation of alkyl radical R into RO2. All the radicals disappeared at the temperature of 160 K. All these processes seem to be the first phases of photoperoxidation of unsaturated fat acids in lipid-containing systems, including biological membranes.", "contents": "[Free radicals formed during UV-irradiation of unsaturated fatty acids containing peroxidation products]. On the irradiation of oxidized linolic acid an assymetric ESR signal with g-factor 2.0039 and the linewidth 30--33 Oe has been registered. The signal could be the result of photolysis of hydroperoxides. During prolonged irradiation of all the samples accumulation of alkyl radicals characterized by a symmetric signal with a well-defined ultrafine structure has been observed. An increase of the sample temperature up to 87 K in the presence of oxygen was preceded by transformation of alkyl radical R into RO2. All the radicals disappeared at the temperature of 160 K. All these processes seem to be the first phases of photoperoxidation of unsaturated fat acids in lipid-containing systems, including biological membranes."}
{"id": "PMID:221053", "title": "[ESR study of mitochondria in basal metabolic states and at different levels of ATP-synthetase activity].", "content": "Effect of metabolic transitions of mitochondria on the value of ESR-absorption measured at room temperature has been studied. It has been found that the content of free radicals with ESR signal of g = 2.00 and the halfwidth about 15e depends on the metabolic state of mitochondria determined by the load of respiration and phosphorylation systems of mitochondria. The maximal gain of the free radical content is observed in the active state when the maximal load is applied to the phosphorylative chain. An attempt to localize the region of initiation of additional free radicals by means of uncouplers and inhibitors of phosphorylation, as well as by placing mitochondria into the phosphate-free medium has shown that the change in ESR absorption of mitochondrion preparation is in a specific correlation with the change in energization of mitochondria. The analysis of alternative ways for an increase of the free radical fund during energization makes it possible to connect this increase with the work of ATP-syntetase and to suggest that free radicals take part in the ADP phosphorylation by inorganic phosphate, being probably, localized directly on the ADP molecule.", "contents": "[ESR study of mitochondria in basal metabolic states and at different levels of ATP-synthetase activity]. Effect of metabolic transitions of mitochondria on the value of ESR-absorption measured at room temperature has been studied. It has been found that the content of free radicals with ESR signal of g = 2.00 and the halfwidth about 15e depends on the metabolic state of mitochondria determined by the load of respiration and phosphorylation systems of mitochondria. The maximal gain of the free radical content is observed in the active state when the maximal load is applied to the phosphorylative chain. An attempt to localize the region of initiation of additional free radicals by means of uncouplers and inhibitors of phosphorylation, as well as by placing mitochondria into the phosphate-free medium has shown that the change in ESR absorption of mitochondrion preparation is in a specific correlation with the change in energization of mitochondria. The analysis of alternative ways for an increase of the free radical fund during energization makes it possible to connect this increase with the work of ATP-syntetase and to suggest that free radicals take part in the ADP phosphorylation by inorganic phosphate, being probably, localized directly on the ADP molecule."}
{"id": "PMID:221057", "title": "Neutrophil-mediated antibody-dependent killing of herpes-simplex-virus-infected cells.", "content": "The ability of neutrophils to serve as effectors of antibody-dependent cell-mediated cytotoxicity (ADCC) was studied using herpes-simplex-virus-infected (HSV-infected) human embryonic lung cells as targets. Killing of infected cells by neutrophils required HSV-immune serum and did not take place in the presence of nonimmune serum or in the absence of serum. Uninfected cells were not killed. ADCC was evident by 30 min and reached a value of 66% by 4 hr at an effector:target ratio of 100:1. Cells from patients with chronic granulomatous disease were as effective as normal cells, and this indicates that ADCC could be mediated by processes that are independent of the respiratory burst.", "contents": "Neutrophil-mediated antibody-dependent killing of herpes-simplex-virus-infected cells. The ability of neutrophils to serve as effectors of antibody-dependent cell-mediated cytotoxicity (ADCC) was studied using herpes-simplex-virus-infected (HSV-infected) human embryonic lung cells as targets. Killing of infected cells by neutrophils required HSV-immune serum and did not take place in the presence of nonimmune serum or in the absence of serum. Uninfected cells were not killed. ADCC was evident by 30 min and reached a value of 66% by 4 hr at an effector:target ratio of 100:1. Cells from patients with chronic granulomatous disease were as effective as normal cells, and this indicates that ADCC could be mediated by processes that are independent of the respiratory burst."}
{"id": "PMID:221058", "title": "Interaction between neuronal amine uptake and prejunctional alpha-adrenergic receptor activation in smooth muscle from canine blood vessels and spleen.", "content": "Experiments were performed to determine the conditions in which norepinephrine release from adrenergic nerve terminals in smooth muscle from canine blood vessels and spleen might be inhibited by prejunctional alpha-adrenergic receptor activation. Strips of aorta, mesenteric and splenic arteries, splenic capsule and portal and saphenous veins were labeled with 7-3H-norepinephrine and mounted for superfusion. In the portal vein, an inhibitory effect of prejunctional receptor activation with exogenous norepinephrine (1.2 X 10(-6) M) on transmitter efflux could be demonstrated during electrical stimulation (9 V, 2 Hz) of the nerve terminals. By contrast, in the other tissues, inhibition of transmitter release during electrical stimulation or depolarization of the nerve terminals with K+ (40 mEq/l) could only be demonstrated aftet blockade of the neuronal uptake mechanism. That activation of prejunctional alpha-adrenergic receptors in blood vessels inhibits the exocytotic process is suggested by the failure of exogenous norepinephrine to affect either the basal efflux of 3-H-norepinephrine or the displacement of 3H-norepinephrine by tyramine.", "contents": "Interaction between neuronal amine uptake and prejunctional alpha-adrenergic receptor activation in smooth muscle from canine blood vessels and spleen. Experiments were performed to determine the conditions in which norepinephrine release from adrenergic nerve terminals in smooth muscle from canine blood vessels and spleen might be inhibited by prejunctional alpha-adrenergic receptor activation. Strips of aorta, mesenteric and splenic arteries, splenic capsule and portal and saphenous veins were labeled with 7-3H-norepinephrine and mounted for superfusion. In the portal vein, an inhibitory effect of prejunctional receptor activation with exogenous norepinephrine (1.2 X 10(-6) M) on transmitter efflux could be demonstrated during electrical stimulation (9 V, 2 Hz) of the nerve terminals. By contrast, in the other tissues, inhibition of transmitter release during electrical stimulation or depolarization of the nerve terminals with K+ (40 mEq/l) could only be demonstrated aftet blockade of the neuronal uptake mechanism. That activation of prejunctional alpha-adrenergic receptors in blood vessels inhibits the exocytotic process is suggested by the failure of exogenous norepinephrine to affect either the basal efflux of 3-H-norepinephrine or the displacement of 3H-norepinephrine by tyramine."}
{"id": "PMID:221059", "title": "Kinetics of alpha-adrenoreceptor blockade by phentolamine in the normal and denervated rabbit aorta and rat vas deferens.", "content": "The rates of onset and offset of alpha-adrenoreceptor blockade by phentolamine (5 X 10(-7) M) have been studied on the normal and denervated rabbit aorta and rat vas deferens. Removal of the adventitia with its accompanying sympathetic nerve component results in an approximately threefold increase in the rate of onset of alpha-adrenoreceptor blockade by phentolamine in the rabbit aorta. The rate of offset of blockade by the antagonist on the aorta is likewise faster after the adventitia has been removed (approximately threefold faster for loss of 90% of the antagonist from the region of the receptors). This effect is not likely to be attributed to the absence of sympathetic nerve terminals since surgical denervation of the rat vas deferens has no effect on the kinetics of receptor blockade in this densely innervated organ. These data suggest that the adventitia of the rabbit aorta may serve as a diffusion barrier which limits the antagonist's access to, and efflux from, the region of the receptors. The dissociation constant of phentolamine (calculated from the equilibrium dose ratio) on the alpha-adrenoreceptor is unaltered by denervation in either tissue and is identical in both tissues. It is suggested that alpha-adrenoreceptors in the rabbit aorta and rat vas deferens are of a single type and are not significantly affected, with respect to antagonist affinity, by denervation.", "contents": "Kinetics of alpha-adrenoreceptor blockade by phentolamine in the normal and denervated rabbit aorta and rat vas deferens. The rates of onset and offset of alpha-adrenoreceptor blockade by phentolamine (5 X 10(-7) M) have been studied on the normal and denervated rabbit aorta and rat vas deferens. Removal of the adventitia with its accompanying sympathetic nerve component results in an approximately threefold increase in the rate of onset of alpha-adrenoreceptor blockade by phentolamine in the rabbit aorta. The rate of offset of blockade by the antagonist on the aorta is likewise faster after the adventitia has been removed (approximately threefold faster for loss of 90% of the antagonist from the region of the receptors). This effect is not likely to be attributed to the absence of sympathetic nerve terminals since surgical denervation of the rat vas deferens has no effect on the kinetics of receptor blockade in this densely innervated organ. These data suggest that the adventitia of the rabbit aorta may serve as a diffusion barrier which limits the antagonist's access to, and efflux from, the region of the receptors. The dissociation constant of phentolamine (calculated from the equilibrium dose ratio) on the alpha-adrenoreceptor is unaltered by denervation in either tissue and is identical in both tissues. It is suggested that alpha-adrenoreceptors in the rabbit aorta and rat vas deferens are of a single type and are not significantly affected, with respect to antagonist affinity, by denervation."}
{"id": "PMID:221060", "title": "In vitro relaxation of arteries and veins by prazosin: alpha-adrenergic blockade with no direct vasodilation.", "content": "Controversy exists regarding the mechanism by which prazosin lowers blood pressure without a marked increase in heart rate; a mechanism involving both sympatholytic activity and direct smooth muscle relaxation has been suggested. alpha-Adrenergic receptor blockade by prazosin is well documented and occurred to exogenous norepinephrine and to field stimulation in vitro in rat arteries and veins. A parallel shift of the norepinephrine concentration response curves in the aorta and mesenteric artery contrasted with a nonparallel shift and a marked depression of maximal norepinephrine responses in the inferior vena cava, portal, iliac and femoral veins. Nonspecific direct acting vasodilators will antagonize contractile responses to all agonists. However, prazosin (10(-8) M) specifically antagonized norepinephrine-induced responses. Concentration response curves to potassium chloride or to serotonin were not affected in these rat tissues. In addition, prazosin (up to 10(-6) M) did not significantly relax aortic tissue previously contracted with potassium chloride or serotonin, whereas the vasodilator, nitroglycerin, produced a clear relaxation. Prazosin only reduced the tone of vessels contracted with norepinephrine. These data indicate that prazosin exhibits minimal, if any, direct smooth muscle relaxant properties in concentrations higher than those producing alpha-adrenergic receptor blockade, and relaxes rat veins by a mechanism involving alpha-adrenergic receptor blockade.", "contents": "In vitro relaxation of arteries and veins by prazosin: alpha-adrenergic blockade with no direct vasodilation. Controversy exists regarding the mechanism by which prazosin lowers blood pressure without a marked increase in heart rate; a mechanism involving both sympatholytic activity and direct smooth muscle relaxation has been suggested. alpha-Adrenergic receptor blockade by prazosin is well documented and occurred to exogenous norepinephrine and to field stimulation in vitro in rat arteries and veins. A parallel shift of the norepinephrine concentration response curves in the aorta and mesenteric artery contrasted with a nonparallel shift and a marked depression of maximal norepinephrine responses in the inferior vena cava, portal, iliac and femoral veins. Nonspecific direct acting vasodilators will antagonize contractile responses to all agonists. However, prazosin (10(-8) M) specifically antagonized norepinephrine-induced responses. Concentration response curves to potassium chloride or to serotonin were not affected in these rat tissues. In addition, prazosin (up to 10(-6) M) did not significantly relax aortic tissue previously contracted with potassium chloride or serotonin, whereas the vasodilator, nitroglycerin, produced a clear relaxation. Prazosin only reduced the tone of vessels contracted with norepinephrine. These data indicate that prazosin exhibits minimal, if any, direct smooth muscle relaxant properties in concentrations higher than those producing alpha-adrenergic receptor blockade, and relaxes rat veins by a mechanism involving alpha-adrenergic receptor blockade."}
{"id": "PMID:221061", "title": "Innervation of the canine inferior vena cava. Distribution of adrenergic and cholinergic excitatory fibers among the embryologically distinct segments.", "content": "The innervation of three embryologically distinct segments of the canine inferior vena cava was investigated. These segments were termed A (supradiaphragm), B-C (intrahepatic and that between liver and renal veins), and D (infrarenal). Strips were cut from these segments, and their isometric tensions were recorded. Transmural electrical stimulation induced contractile responses in circular strips from segment B-C (66.5% of the maximum norepinephrine-induced response) and in those from D (14.4%), but not in A. These responses almost completely disappeared in the presence of phenoxybenzamine. In segment B-C, however, the remaining small contraction was markedly enhanced by neostigmine and abolished by atropine. The same phenomenon was also observed in the contraction remaining after reserpinization. Longitudinal strips from segment C responded similarly. Concentration-response curves of circular strips for acetylcholine were shifted by neostigmine markedly to the left only in segment B-C, while no significant shift occurred in A and D. It was concluded that the adrenergic innervation is remarkably dense in B-C, sparse in D, and probably lacking in A. In addition, a cholinergic excitatory innervation is present in segment B-C.", "contents": "Innervation of the canine inferior vena cava. Distribution of adrenergic and cholinergic excitatory fibers among the embryologically distinct segments. The innervation of three embryologically distinct segments of the canine inferior vena cava was investigated. These segments were termed A (supradiaphragm), B-C (intrahepatic and that between liver and renal veins), and D (infrarenal). Strips were cut from these segments, and their isometric tensions were recorded. Transmural electrical stimulation induced contractile responses in circular strips from segment B-C (66.5% of the maximum norepinephrine-induced response) and in those from D (14.4%), but not in A. These responses almost completely disappeared in the presence of phenoxybenzamine. In segment B-C, however, the remaining small contraction was markedly enhanced by neostigmine and abolished by atropine. The same phenomenon was also observed in the contraction remaining after reserpinization. Longitudinal strips from segment C responded similarly. Concentration-response curves of circular strips for acetylcholine were shifted by neostigmine markedly to the left only in segment B-C, while no significant shift occurred in A and D. It was concluded that the adrenergic innervation is remarkably dense in B-C, sparse in D, and probably lacking in A. In addition, a cholinergic excitatory innervation is present in segment B-C."}
{"id": "PMID:221062", "title": "In vivo effect of endrin on three phosphatases in kidney and liver of the fish Ophiocephalus punctatus.", "content": "The effect of endrin (0.030 ppm) on the acid phosphatase, alkaline phosphatase and glucose-6-phosphatase activities in the kidney and liver of a teleost fish, Ophiocephalus (Channa) punctatus has been studied. The period of exposure was twenty days. An increase in the acid phosphatase activity is noted in the two tissues examined here. There is no significant change in the activity of alkaline phosphatase in kidney while in liver the enzyme is inhibited. In the kidney glucose-6-phosphatase showed a slight increase in activity but it is inhibited in liver.", "contents": "In vivo effect of endrin on three phosphatases in kidney and liver of the fish Ophiocephalus punctatus. The effect of endrin (0.030 ppm) on the acid phosphatase, alkaline phosphatase and glucose-6-phosphatase activities in the kidney and liver of a teleost fish, Ophiocephalus (Channa) punctatus has been studied. The period of exposure was twenty days. An increase in the acid phosphatase activity is noted in the two tissues examined here. There is no significant change in the activity of alkaline phosphatase in kidney while in liver the enzyme is inhibited. In the kidney glucose-6-phosphatase showed a slight increase in activity but it is inhibited in liver."}
{"id": "PMID:221066", "title": "Effects of childhood cancer on long-term survivors and their families.", "content": "Problems experienced by families of long-term survivors of acute lymphatic leukaemia and Wilms's tumour were investigated to find out the best way of using limited resources to improve management of such patients. All patients had received treatment at Alder Hey Children's Hospital, and all had completed treatment at least two years before the study. A social worker interviewed the parents of each child. The results showed that various aspects of management needed improvement, including: information given to parents at diagnosis of their child's illness and during subsequent treatment; continuity of care and multidisciplinary teamwork among those caring for the child; greater understanding by school teachers that such children have the same educational needs as others; wider communication by hospital staff with the child's other relatives, particularly grandparents; financial help for parents; and marital counselling. To help implement these proposals full-time social workers were attached to the hospital. Preliminary results were encouraging, though it is too early to evaluate the long-term effects of the changes.", "contents": "Effects of childhood cancer on long-term survivors and their families. Problems experienced by families of long-term survivors of acute lymphatic leukaemia and Wilms's tumour were investigated to find out the best way of using limited resources to improve management of such patients. All patients had received treatment at Alder Hey Children's Hospital, and all had completed treatment at least two years before the study. A social worker interviewed the parents of each child. The results showed that various aspects of management needed improvement, including: information given to parents at diagnosis of their child's illness and during subsequent treatment; continuity of care and multidisciplinary teamwork among those caring for the child; greater understanding by school teachers that such children have the same educational needs as others; wider communication by hospital staff with the child's other relatives, particularly grandparents; financial help for parents; and marital counselling. To help implement these proposals full-time social workers were attached to the hospital. Preliminary results were encouraging, though it is too early to evaluate the long-term effects of the changes."}
{"id": "PMID:221070", "title": "Substance P: depletion in the dorsal horn of rat spinal cord after section of the peripheral processes of primary sensory neurons.", "content": "The substance P content, glutamic acid decarboxylase and choline acetyltransferase activities and the level of [3H]diprenorphine binding were measured in various regions of the lumbar spinal cord of rats after unilateral section of the sciatic nerve or after dorsal rhizotomy. Sciatic nerve section produced a 75--80% depletion of substance P in the dorsal horn but did not change the substance P content of the ventral horn. The onset of substance P depletion occurred within 7 days and was maintained for 2 months. The substance P content of the dorsal root ganglia and both the peripheral and central branches of primary sensory neurons was also reduced after sciatic nerve section. Glutamic acid decarboxylase and choline acetyltransferase activity were unchanged; however, a small decrease in opiate receptor binding occurred 1 month after nerve section. Dorsal rhizotomy produced an 80% depletion of substance P in the dorsal horn. In addition, the substance P content of the ventral horn was significantly reduced. Glutamic acid decarboxylase activity in the dorsal horn was unaffected by dorsal rhizotomy whereas opiate receptor binding was reduced by 40%. From these studies it appears that peripheral nerve injury results in the degeneration of primary sensory neurons which contain and release substance P as neurotransmitter.", "contents": "Substance P: depletion in the dorsal horn of rat spinal cord after section of the peripheral processes of primary sensory neurons. The substance P content, glutamic acid decarboxylase and choline acetyltransferase activities and the level of [3H]diprenorphine binding were measured in various regions of the lumbar spinal cord of rats after unilateral section of the sciatic nerve or after dorsal rhizotomy. Sciatic nerve section produced a 75--80% depletion of substance P in the dorsal horn but did not change the substance P content of the ventral horn. The onset of substance P depletion occurred within 7 days and was maintained for 2 months. The substance P content of the dorsal root ganglia and both the peripheral and central branches of primary sensory neurons was also reduced after sciatic nerve section. Glutamic acid decarboxylase and choline acetyltransferase activity were unchanged; however, a small decrease in opiate receptor binding occurred 1 month after nerve section. Dorsal rhizotomy produced an 80% depletion of substance P in the dorsal horn. In addition, the substance P content of the ventral horn was significantly reduced. Glutamic acid decarboxylase activity in the dorsal horn was unaffected by dorsal rhizotomy whereas opiate receptor binding was reduced by 40%. From these studies it appears that peripheral nerve injury results in the degeneration of primary sensory neurons which contain and release substance P as neurotransmitter."}
{"id": "PMID:221071", "title": "Infundibular localization of vasopressin, oxytocin and neurophysins in the rat; its relationships with corticotrope function.", "content": "The distribution of vasopressin (VP), oxytocin (OXY) and neurophysins 1 and 2 (N1, N2) has been studied in the median eminence (ME) of normal, heterozygous (HDI) and Brattleboro (DI) rats. Numerous thin periportal VP and N2 fibres exist in the normal and HD1 rats; they have never been observed in the DI rats. N1 and OXY fibres in the external layer of the median eminence are rare. Adrenalectomy increases periportal VP and N2 loading in normal and HDI rats; it does not modify the appearance of the DI median eminence. Dexamethasone prevents external VP and N2 overloading in adrenalectomized rats injected during the whole postoperative period. Injections of vasopressin indicated that it had a negative feedback effect during a short time (3 days) but not during a longer period (7 days). The suprachiasmatic neurons are stained only by anti-VP and anti-N2 antibodies. Their overstaining induced by adrenalectomy disappears with dexamethasone, aldosterone or vasopressin treatment. This central effect of hormones is not necessarily associated with disappearance of overloading in the external layer of the ME. The hypothalamo-infundibular tract carrying VP and N2 is involved in regulatory mechanisms of the corticotrope axis. Its relationships with suprachiasmatic neurons are discussed.", "contents": "Infundibular localization of vasopressin, oxytocin and neurophysins in the rat; its relationships with corticotrope function. The distribution of vasopressin (VP), oxytocin (OXY) and neurophysins 1 and 2 (N1, N2) has been studied in the median eminence (ME) of normal, heterozygous (HDI) and Brattleboro (DI) rats. Numerous thin periportal VP and N2 fibres exist in the normal and HD1 rats; they have never been observed in the DI rats. N1 and OXY fibres in the external layer of the median eminence are rare. Adrenalectomy increases periportal VP and N2 loading in normal and HDI rats; it does not modify the appearance of the DI median eminence. Dexamethasone prevents external VP and N2 overloading in adrenalectomized rats injected during the whole postoperative period. Injections of vasopressin indicated that it had a negative feedback effect during a short time (3 days) but not during a longer period (7 days). The suprachiasmatic neurons are stained only by anti-VP and anti-N2 antibodies. Their overstaining induced by adrenalectomy disappears with dexamethasone, aldosterone or vasopressin treatment. This central effect of hormones is not necessarily associated with disappearance of overloading in the external layer of the ME. The hypothalamo-infundibular tract carrying VP and N2 is involved in regulatory mechanisms of the corticotrope axis. Its relationships with suprachiasmatic neurons are discussed."}
{"id": "PMID:221072", "title": "Cerebellar opiate receptors in lagomorphs. Demonstration, characterization and regional distribution.", "content": "The cerebellum of lagomorphs (pika, rabbit, hare) binds 100--200 femtomoles of [3H]etorphine per milligram of protein. This is very high in comparison with the 10--15 fmol/mg found in the cerebellum of rodents (mouse, hamster, rat). In the rabbit cerebellum, the etorphine sites have binding properties indistinguishable from those of genuine opiate receptor sites in brain. They exhibit a high affinity for [3H]etorphine (KD = 1 X 10(-10) M), [3H]naloxone (KD = 9 X 10(-10) M), morphine and levorphanol but not for dextrophan. Moreover, sodium ions enhance binding of naloxone (antagonist response) and diminish binding of etorphine, morphine and levorphanol (agonist response) to cerebellum homogenates. The regional distribution of [3H]etorphine binding sites in the rabbit cerebellum points toward concentrations higher in the neocerebellum (hemispheres) than in the archecerebellum (lingula and flocculonodular lobe). Finally, the specific concentration of opiate receptor sites in the isolated molecular layer is at least two times that in the isolated granular layer and ten times that in white matter.", "contents": "Cerebellar opiate receptors in lagomorphs. Demonstration, characterization and regional distribution. The cerebellum of lagomorphs (pika, rabbit, hare) binds 100--200 femtomoles of [3H]etorphine per milligram of protein. This is very high in comparison with the 10--15 fmol/mg found in the cerebellum of rodents (mouse, hamster, rat). In the rabbit cerebellum, the etorphine sites have binding properties indistinguishable from those of genuine opiate receptor sites in brain. They exhibit a high affinity for [3H]etorphine (KD = 1 X 10(-10) M), [3H]naloxone (KD = 9 X 10(-10) M), morphine and levorphanol but not for dextrophan. Moreover, sodium ions enhance binding of naloxone (antagonist response) and diminish binding of etorphine, morphine and levorphanol (agonist response) to cerebellum homogenates. The regional distribution of [3H]etorphine binding sites in the rabbit cerebellum points toward concentrations higher in the neocerebellum (hemispheres) than in the archecerebellum (lingula and flocculonodular lobe). Finally, the specific concentration of opiate receptor sites in the isolated molecular layer is at least two times that in the isolated granular layer and ten times that in white matter."}
{"id": "PMID:221075", "title": "Effect of nerve activity on the in vivo release of [3H]serotonin continuously formed from L-[3H]tryptophan in the caudate nucleus of the cat.", "content": "A new isotopic approach has been developed to study the in vivo release of serotonin (5-HT). 'Enc\u00e9phale isol\u00e9' cats were implanted with a push-pull cannula in the ventrocaudal part of the head of the caudate nucleus to estimate the release of [3H]5-HT continuously synthesized from L-[3H]tryptophan. Both [3H]5-HT and [3H]tryptamine were found in superfusates. Resting steady state in the release of [3H]indoleamines was observed as soon as 20 min after the beginning of the superfusion with L-[3H]tryptophan; the levels of [3H]5-HT in superfusates were 2.5 times those of [3H]tryptamine and about 6 times the blank value. They were markedly enhanced in the presence of fluoxetine (5 x 10(-6)M), a blocker of the 5-HT uptake process. A marked increase in the release of [3H]5-HT was seen during the local depolarization of 5-HT terminals with potassium chloride (60 mM) or batrachotoxin (10(-6)M) or during the stimulation of 5-HT cell bodies in the nucleus raphe dorsalis with L-glutamic acid (5 x 10(-5)M). These treatments did not enhance the efflux of [3H]tryptamine. The potassium-evoked release of [3H]5-HT was reduced by LSD (10(-5)M). LSD added alone in the superfusing fluid was without effect. The batrachotoxin-evoked release of [3H]5-HT was inhibited in the presence of tetrodotoxin (9 x 10(-6)M). The spontaneous release of [3H]5-HT and [3H]tryptamine was markedly reduced in the presence of a calcium-free medium containing cobalt (10 mM). A transient slight reduction in the spontaneous release of [3H]5-HT was observed in the presence of tetrodotoxin (9 x 10(-6)M). The local cooling of 5-HT cell bodies with a cryoelectrode induced a slight reversible decrease in [3H]5-HT release. These last two treatments were without significant effect on [3H]tryptamine efflux in superfusates. These results indicate that the release of [3H]5-HT endogenously formed from [3H]tryptophan is dependent on nerve activity and that this is not the case for [3H]tryptamine. The advantages of the isotopic approach for in vivo studies on the release of 5-HT are discussed.", "contents": "Effect of nerve activity on the in vivo release of [3H]serotonin continuously formed from L-[3H]tryptophan in the caudate nucleus of the cat. A new isotopic approach has been developed to study the in vivo release of serotonin (5-HT). 'Enc\u00e9phale isol\u00e9' cats were implanted with a push-pull cannula in the ventrocaudal part of the head of the caudate nucleus to estimate the release of [3H]5-HT continuously synthesized from L-[3H]tryptophan. Both [3H]5-HT and [3H]tryptamine were found in superfusates. Resting steady state in the release of [3H]indoleamines was observed as soon as 20 min after the beginning of the superfusion with L-[3H]tryptophan; the levels of [3H]5-HT in superfusates were 2.5 times those of [3H]tryptamine and about 6 times the blank value. They were markedly enhanced in the presence of fluoxetine (5 x 10(-6)M), a blocker of the 5-HT uptake process. A marked increase in the release of [3H]5-HT was seen during the local depolarization of 5-HT terminals with potassium chloride (60 mM) or batrachotoxin (10(-6)M) or during the stimulation of 5-HT cell bodies in the nucleus raphe dorsalis with L-glutamic acid (5 x 10(-5)M). These treatments did not enhance the efflux of [3H]tryptamine. The potassium-evoked release of [3H]5-HT was reduced by LSD (10(-5)M). LSD added alone in the superfusing fluid was without effect. The batrachotoxin-evoked release of [3H]5-HT was inhibited in the presence of tetrodotoxin (9 x 10(-6)M). The spontaneous release of [3H]5-HT and [3H]tryptamine was markedly reduced in the presence of a calcium-free medium containing cobalt (10 mM). A transient slight reduction in the spontaneous release of [3H]5-HT was observed in the presence of tetrodotoxin (9 x 10(-6)M). The local cooling of 5-HT cell bodies with a cryoelectrode induced a slight reversible decrease in [3H]5-HT release. These last two treatments were without significant effect on [3H]tryptamine efflux in superfusates. These results indicate that the release of [3H]5-HT endogenously formed from [3H]tryptophan is dependent on nerve activity and that this is not the case for [3H]tryptamine. The advantages of the isotopic approach for in vivo studies on the release of 5-HT are discussed."}
{"id": "PMID:221076", "title": "Chronic relapsing experimental allergic encephalomyelitis: morphological sequence of myelin degradation.", "content": "Myelin degradation in chronic relapsing experimental allergic encephalomyelitis was studied using light microscopic histochemistry and electron microscopy. In the earliest stages, a large number of myelin stripping macrophages were found. The Luxol fast blue positive degradation products were then gradually transformed into PAS positive material. No sudanophilic stage of myelin degradation was found in this model. In electron microscopy, the Luxol fast blue positive material was identified as uniformly layered lipid inclusions with a periodicity of 4.0--4.5 nm. During further digestion, this material was transformed into polymorph structured material, consisting of lamellar leaflets with a diameter of 7--10 nm, curved cylindrical profiles and granular osmiophilic material.", "contents": "Chronic relapsing experimental allergic encephalomyelitis: morphological sequence of myelin degradation. Myelin degradation in chronic relapsing experimental allergic encephalomyelitis was studied using light microscopic histochemistry and electron microscopy. In the earliest stages, a large number of myelin stripping macrophages were found. The Luxol fast blue positive degradation products were then gradually transformed into PAS positive material. No sudanophilic stage of myelin degradation was found in this model. In electron microscopy, the Luxol fast blue positive material was identified as uniformly layered lipid inclusions with a periodicity of 4.0--4.5 nm. During further digestion, this material was transformed into polymorph structured material, consisting of lamellar leaflets with a diameter of 7--10 nm, curved cylindrical profiles and granular osmiophilic material."}
{"id": "PMID:221079", "title": "Effects of parachlorophenylalanine and 5, 6-dihydroxytryptamine on the free-running rhythms of locomotor activity and plasma corticosterone in the rat exposed to continuous light.", "content": "Parachlorophenylalanine (PCPA) and 5,6-dihydroxytryptamine (5,6-DHT), depletors of brain serotonin, were administered to the rat and circadian rhythms of locomotor activity and plasma corticosterone were determined simultaneously in individual rats in light-dark cycles (LD) and in 200 lux continuous light (LL). Free-running periods and acrophases on the 12th day in LL (LL12) were calculated by a least squares spectrum method. In PCPA-treated rats which showed 70% depletion of brain serotonin, circadian rhythms of locomotor activity in LL and of plasma corticosterone and ACTH in LD disappeared for several days after the drug injection. Circadian rhythms of locomotor activity reappeared after the LL7 day and free-ran with a phase shift. Free-running periods of these rats did not differ significantly from that of control rats. However, the acrophase of PCPA-treated group on the LL11 day was 5 h advanced as compared to that of control. Circadian rhythm of plasma corticosterone in the PCPA-treated rats was detected on the LL12 day but their peak times were distributed around 24:00 h instead 08:00 h observed rats. The 5,6-DHT-treated rats which showed only 40% depletion of brain serotonin exhibited normal free-running rhythms in both locomotor activity and plasma corticosterone in LL and no difference in the acrophases of these functions on the LL12 day as compared to controls. These results suggest that PCPA affects the circadian clock (or clocks) itself in such a way that it blocks the clock to free-run or at least it effectively shortens the free-running periods of locomotor activity and plasma corticosterone in the rat.", "contents": "Effects of parachlorophenylalanine and 5, 6-dihydroxytryptamine on the free-running rhythms of locomotor activity and plasma corticosterone in the rat exposed to continuous light. Parachlorophenylalanine (PCPA) and 5,6-dihydroxytryptamine (5,6-DHT), depletors of brain serotonin, were administered to the rat and circadian rhythms of locomotor activity and plasma corticosterone were determined simultaneously in individual rats in light-dark cycles (LD) and in 200 lux continuous light (LL). Free-running periods and acrophases on the 12th day in LL (LL12) were calculated by a least squares spectrum method. In PCPA-treated rats which showed 70% depletion of brain serotonin, circadian rhythms of locomotor activity in LL and of plasma corticosterone and ACTH in LD disappeared for several days after the drug injection. Circadian rhythms of locomotor activity reappeared after the LL7 day and free-ran with a phase shift. Free-running periods of these rats did not differ significantly from that of control rats. However, the acrophase of PCPA-treated group on the LL11 day was 5 h advanced as compared to that of control. Circadian rhythm of plasma corticosterone in the PCPA-treated rats was detected on the LL12 day but their peak times were distributed around 24:00 h instead 08:00 h observed rats. The 5,6-DHT-treated rats which showed only 40% depletion of brain serotonin exhibited normal free-running rhythms in both locomotor activity and plasma corticosterone in LL and no difference in the acrophases of these functions on the LL12 day as compared to controls. These results suggest that PCPA affects the circadian clock (or clocks) itself in such a way that it blocks the clock to free-run or at least it effectively shortens the free-running periods of locomotor activity and plasma corticosterone in the rat."}
{"id": "PMID:221084", "title": "Spectral studies of human erythrocyte catalase.", "content": "The optical absorption and circular dichroic spectra of human erythrocyte catalase (EC 1.11.1.6) and its cyanide, azide, and fluoride derivatives over the wavelength range of 210 to 700 nm are reported. Treatment with acid or alkaline solutions causes spectral changes which may be due to dissociation of the enzyme into subunits and removal of the heme group from the protein. The fractions of the protein structure present as alpha helix, beta pleated sheet, and unordered structure have been estimated from the CD spectrum in the far-ultraviolet region. The CD spectra also indicate that the protein conformation does not change appreciably after cyanide binding. The epr spectroscopy of the native enzyme and its cyanide complex are reported. The spectral results are compared with catalase obtained from other mammalian and bacterial sources.", "contents": "Spectral studies of human erythrocyte catalase. The optical absorption and circular dichroic spectra of human erythrocyte catalase (EC 1.11.1.6) and its cyanide, azide, and fluoride derivatives over the wavelength range of 210 to 700 nm are reported. Treatment with acid or alkaline solutions causes spectral changes which may be due to dissociation of the enzyme into subunits and removal of the heme group from the protein. The fractions of the protein structure present as alpha helix, beta pleated sheet, and unordered structure have been estimated from the CD spectrum in the far-ultraviolet region. The CD spectra also indicate that the protein conformation does not change appreciably after cyanide binding. The epr spectroscopy of the native enzyme and its cyanide complex are reported. The spectral results are compared with catalase obtained from other mammalian and bacterial sources."}
{"id": "PMID:221085", "title": "Gangliocytic paraganglioma of the duodenum.", "content": "In spite of possessing microscopic features of invasiveness, the clinical behaviour of duodenal gangliocytic paraganglioma is benign. The operation of choice for removal of the tumour is local excision. This conservative approach was used in the case of a 70-year-old white women who presented with occult gastrointestinal bleeding. The unusual histologic features of this woman's tumour are discussed. Although the tumour appears to be aggressive no recurrence has been reported to date following adequate local excision of a duodenal gangliocytic paraganglioma.", "contents": "Gangliocytic paraganglioma of the duodenum. In spite of possessing microscopic features of invasiveness, the clinical behaviour of duodenal gangliocytic paraganglioma is benign. The operation of choice for removal of the tumour is local excision. This conservative approach was used in the case of a 70-year-old white women who presented with occult gastrointestinal bleeding. The unusual histologic features of this woman's tumour are discussed. Although the tumour appears to be aggressive no recurrence has been reported to date following adequate local excision of a duodenal gangliocytic paraganglioma."}
{"id": "PMID:221087", "title": "Effects of irradiation on mixed m\u00fcllerian tumors of the uterus.", "content": "A retrospective study of 54 patients with histologically proven malignant mixed m\u00fcllerian tumors of the uterus was undertaken with main emphasis on the evaluation of the effects of irradiation on pelvic tumor control. The tumors were staged according to the FIGO classification for endometrial carcinoma and 24 were classified as Stage I, 10 as Stage II, 13 as Stage III and seven as Stage IV. Patients with Stage I and II were treated with surgery alone (9 patients, three surviving) or preoperative intracavitary irradiation (13 patients, eight surviving) or preoperative combination of intracavitary and external irradiation (12 patients, six surviving). Five patients with Stage III and IV were treated with surgery alone, two were treated with a combination of irradiation and surgery and 11 with radiation alone. None of these patients survived. In seven patients showing no residual tumor in the uterine specimen after irradiation, no pelvic failures were noted, whereas seven of 17 (41.2%) with residual tumor developed pelvic recurrences. In patients with Stage I treated with surgery alone, three out of six recurred in the pelvis whereas only three of 17 (17%) receiving preoperative irradiation developed pelvic recurrences. However, in Stage II six of eight patients treated with preoperative irradiation failed in the pelvis. Correlation with the doses of irradiation given to the uterus or the pelvic lymph nodes indicate that with doses below 5000 rads a significantly higher number of pelvic recurrences take place, whereas these are uncommon with doses over 6000 rads. The difference in pelvic recurrences between dosage levels is not, however, statistically significant. It is suggested that patients with Stage I and II malignant mixed m\u00fcllerian tumors of the uterus should be treated with preoperative radiation and total hysterectomy with bilateral salpingo-oophorectomy. Patients with more  advanced disease have extremely poor prognosis and should be treated with radiation therapy alone. This tumor has a high propensity to spread through lymphatics and hematogenous metastases are seen in approximately 75% of the patients. Because of this dissemination, significant improvements in survival rate will not be seen until effective cytotoxic agents are available.", "contents": "Effects of irradiation on mixed m\u00fcllerian tumors of the uterus. A retrospective study of 54 patients with histologically proven malignant mixed m\u00fcllerian tumors of the uterus was undertaken with main emphasis on the evaluation of the effects of irradiation on pelvic tumor control. The tumors were staged according to the FIGO classification for endometrial carcinoma and 24 were classified as Stage I, 10 as Stage II, 13 as Stage III and seven as Stage IV. Patients with Stage I and II were treated with surgery alone (9 patients, three surviving) or preoperative intracavitary irradiation (13 patients, eight surviving) or preoperative combination of intracavitary and external irradiation (12 patients, six surviving). Five patients with Stage III and IV were treated with surgery alone, two were treated with a combination of irradiation and surgery and 11 with radiation alone. None of these patients survived. In seven patients showing no residual tumor in the uterine specimen after irradiation, no pelvic failures were noted, whereas seven of 17 (41.2%) with residual tumor developed pelvic recurrences. In patients with Stage I treated with surgery alone, three out of six recurred in the pelvis whereas only three of 17 (17%) receiving preoperative irradiation developed pelvic recurrences. However, in Stage II six of eight patients treated with preoperative irradiation failed in the pelvis. Correlation with the doses of irradiation given to the uterus or the pelvic lymph nodes indicate that with doses below 5000 rads a significantly higher number of pelvic recurrences take place, whereas these are uncommon with doses over 6000 rads. The difference in pelvic recurrences between dosage levels is not, however, statistically significant. It is suggested that patients with Stage I and II malignant mixed m\u00fcllerian tumors of the uterus should be treated with preoperative radiation and total hysterectomy with bilateral salpingo-oophorectomy. Patients with more  advanced disease have extremely poor prognosis and should be treated with radiation therapy alone. This tumor has a high propensity to spread through lymphatics and hematogenous metastases are seen in approximately 75% of the patients. Because of this dissemination, significant improvements in survival rate will not be seen until effective cytotoxic agents are available."}
{"id": "PMID:221088", "title": "Adjuvant immunotherapy of lung cancer with BCG cell wall skeleton (BCG-CWS).", "content": "Four hundred fifty-five patients with lung cancer were treated with oil-attached cell-wall skeleton of bacillus Calmette-Gu\u00e9rin (BCG-CWS) as adjuvant immunotherapy following initial conventional therapy. The overall survival period of the patients was prolonged significantly as compared with that of 380 patients in a historical control group receiving initial conventional therapy alone (p less than 0.0001). The prolongation of the survival period of the patients was also statistically significant when classified according to clinical stages and histological cell types. The therapeutic effect was remarkable in patients combined with malignant pleurisy. Intrapleural injection of BCG-CWS resulted in not only prevention of accumulation of pleural effusion and abrogation of tumor cells but also in prolongation of survival period (P = 0.016). No serious side effects due to BCG-CWS were experienced. From the previous experimental studies and clinical experiences with human tumors, it can be concluded that adjuvant immunotherapy with BCG-CWS is a useful therapeutic modality for lung cancer, especially in cases combined with malignant pleurisy.", "contents": "Adjuvant immunotherapy of lung cancer with BCG cell wall skeleton (BCG-CWS). Four hundred fifty-five patients with lung cancer were treated with oil-attached cell-wall skeleton of bacillus Calmette-Gu\u00e9rin (BCG-CWS) as adjuvant immunotherapy following initial conventional therapy. The overall survival period of the patients was prolonged significantly as compared with that of 380 patients in a historical control group receiving initial conventional therapy alone (p less than 0.0001). The prolongation of the survival period of the patients was also statistically significant when classified according to clinical stages and histological cell types. The therapeutic effect was remarkable in patients combined with malignant pleurisy. Intrapleural injection of BCG-CWS resulted in not only prevention of accumulation of pleural effusion and abrogation of tumor cells but also in prolongation of survival period (P = 0.016). No serious side effects due to BCG-CWS were experienced. From the previous experimental studies and clinical experiences with human tumors, it can be concluded that adjuvant immunotherapy with BCG-CWS is a useful therapeutic modality for lung cancer, especially in cases combined with malignant pleurisy."}
{"id": "PMID:221089", "title": "Malignant melanotic neuroectodermal tumor of infancy: a clinical, pathologic, ultrastructural and tissue culture study.", "content": "The melanotic neuroectodermal tumor of infancy is an uncommon neoplasm typically of early childhood which has a predilection for the head and neck region, particularly the maxilla. Except for one previous example in the literature, this tumor has consistently behaved in a benign fashion. This study documents the clinical course and pathologic findings of a tumor which began in the maxilla of a 4-month-old boy, followed by a local recurrence, metastasis to a cervical lymph node and finally, widespread dissemination and death at 18 months, 24 months and 38 months, respectively. The tumor was initially composed of nests consisting of melanin-containing cells and small dark cells. An elevated vanillylmandelic acid level was recorded during the course of the disease. At autopsy, the tumor in lymph nodes, liver, bone and soft tissues had a monotonous pattern of small dark cells similar to a conventional neuroblastoma. Previous ultrastructural studies indicate that the melanotic neuroectodermal tumor of infancy is composed of melanocytes and neuroblast-like cells. Our case provided the unique opportunity to examine in sequence the ultrastructural and in vitro characteristics of a recurring and eventually metastasizing melanotic neuroectodermal tumor. Although the neuroblast-like cells were initially difficult to identify by electron microscopy, a melanin-producing cell line and a separate nonpigmented cell line were successfully isolated from various tumor explants. Various stages of melanosome development were identified in the pigmented cells from the local recurrences and in vitro. Dibutyryl cAMP accentuated the formation of pigment and dendritic development in the melanocytes and dendrites only in the small nonpigmented cells. Electron dense granules were observed in the cultured smaller cells and also in the lymph node and soft tissue metastases. Tyrosine hydroxylase activity was demonstrated in the neuroblast-like cells. In the final biopsy and autopsy material, only the neuroblast-like cells remained and the tumor resembled a conventional neuroblastoma.", "contents": "Malignant melanotic neuroectodermal tumor of infancy: a clinical, pathologic, ultrastructural and tissue culture study. The melanotic neuroectodermal tumor of infancy is an uncommon neoplasm typically of early childhood which has a predilection for the head and neck region, particularly the maxilla. Except for one previous example in the literature, this tumor has consistently behaved in a benign fashion. This study documents the clinical course and pathologic findings of a tumor which began in the maxilla of a 4-month-old boy, followed by a local recurrence, metastasis to a cervical lymph node and finally, widespread dissemination and death at 18 months, 24 months and 38 months, respectively. The tumor was initially composed of nests consisting of melanin-containing cells and small dark cells. An elevated vanillylmandelic acid level was recorded during the course of the disease. At autopsy, the tumor in lymph nodes, liver, bone and soft tissues had a monotonous pattern of small dark cells similar to a conventional neuroblastoma. Previous ultrastructural studies indicate that the melanotic neuroectodermal tumor of infancy is composed of melanocytes and neuroblast-like cells. Our case provided the unique opportunity to examine in sequence the ultrastructural and in vitro characteristics of a recurring and eventually metastasizing melanotic neuroectodermal tumor. Although the neuroblast-like cells were initially difficult to identify by electron microscopy, a melanin-producing cell line and a separate nonpigmented cell line were successfully isolated from various tumor explants. Various stages of melanosome development were identified in the pigmented cells from the local recurrences and in vitro. Dibutyryl cAMP accentuated the formation of pigment and dendritic development in the melanocytes and dendrites only in the small nonpigmented cells. Electron dense granules were observed in the cultured smaller cells and also in the lymph node and soft tissue metastases. Tyrosine hydroxylase activity was demonstrated in the neuroblast-like cells. In the final biopsy and autopsy material, only the neuroblast-like cells remained and the tumor resembled a conventional neuroblastoma."}
{"id": "PMID:221090", "title": "Adenosarcoma of uterus and ovary: a clinicopathologic study of two cases.", "content": "We report the clinical and pathologic features of two cases of adenosarcoma. Our first case occurred in the ovary of a 51-year-old woman with extensive pelvic involvement. She was treated vigorously with radiation and chemotherapy and at the present time almost 9 years later the patient is free of disease. This represents a case with one of the longest survival reported in the literature. Our second case occurred in a 37-year-old woman and was limited to the endometrium.", "contents": "Adenosarcoma of uterus and ovary: a clinicopathologic study of two cases. We report the clinical and pathologic features of two cases of adenosarcoma. Our first case occurred in the ovary of a 51-year-old woman with extensive pelvic involvement. She was treated vigorously with radiation and chemotherapy and at the present time almost 9 years later the patient is free of disease. This represents a case with one of the longest survival reported in the literature. Our second case occurred in a 37-year-old woman and was limited to the endometrium."}
{"id": "PMID:221091", "title": "Adenoid cystic carcinoma: biologic behavior in 38 patients.", "content": "This study presents the clinical and pathologic data on 38 patients with adenoid cystic carcinoma. Most of the tumors arose from the major salivary glands or the mucus glands of the upper respiratory tract and oral cavity. The typical biological behavior of these tumors was slow but aggressive local growth despite all therapy, followed by eventual death from local disease and/or metastases. Twenty-eight of the patients have died, 22 from adenoic cystic carcinoma, 3 from postoperative complications, and 3 from intercurrent disease. Of the 10 living patients, 4 have active disease, 2 have no evidence of disease 14 years after diagnosis, and 4 have no evidence of disease but follow-up is less than 5 years. We compared various microscopic features of the tumors, including histologic grading, with prognosis but did not demonstrate a correlation in this small series.", "contents": "Adenoid cystic carcinoma: biologic behavior in 38 patients. This study presents the clinical and pathologic data on 38 patients with adenoid cystic carcinoma. Most of the tumors arose from the major salivary glands or the mucus glands of the upper respiratory tract and oral cavity. The typical biological behavior of these tumors was slow but aggressive local growth despite all therapy, followed by eventual death from local disease and/or metastases. Twenty-eight of the patients have died, 22 from adenoic cystic carcinoma, 3 from postoperative complications, and 3 from intercurrent disease. Of the 10 living patients, 4 have active disease, 2 have no evidence of disease 14 years after diagnosis, and 4 have no evidence of disease but follow-up is less than 5 years. We compared various microscopic features of the tumors, including histologic grading, with prognosis but did not demonstrate a correlation in this small series."}
{"id": "PMID:221092", "title": "Hodgkin's disease terminating in oat cell carcinoma of the lung.", "content": "A 27-year-old woman with Hodgkin's disease, nodular sclerasing type, having received two courses of radiation therapy with one year and nine months interval and a prolonged course of chemotherapy with combinations of COPP, MOPP and CVPP, developed oat cell carcinoma of the lung, four years after the initial diagnosis.", "contents": "Hodgkin's disease terminating in oat cell carcinoma of the lung. A 27-year-old woman with Hodgkin's disease, nodular sclerasing type, having received two courses of radiation therapy with one year and nine months interval and a prolonged course of chemotherapy with combinations of COPP, MOPP and CVPP, developed oat cell carcinoma of the lung, four years after the initial diagnosis."}
{"id": "PMID:221094", "title": "Partial remission of advanced adenoid cystic carcinoma obtained with adriamycin: a case report with a review of the literature.", "content": "Adenoid cystic carcinoma is relatively uncommon and often originates from the salivary glands. Although distant metastases develop rather frequently no satisfactory form of therapy has been reported. We achieved a partial remission with adriamycin in a patient with advanced metastases of adenoid cystic carcinoma. This case is described, and a short review of the literature, including papers on the treatment of advanced disease, is also given.", "contents": "Partial remission of advanced adenoid cystic carcinoma obtained with adriamycin: a case report with a review of the literature. Adenoid cystic carcinoma is relatively uncommon and often originates from the salivary glands. Although distant metastases develop rather frequently no satisfactory form of therapy has been reported. We achieved a partial remission with adriamycin in a patient with advanced metastases of adenoid cystic carcinoma. This case is described, and a short review of the literature, including papers on the treatment of advanced disease, is also given."}
{"id": "PMID:221095", "title": "Trophoblastic pseudotumor of the uterus: case report and ultrastructure.", "content": "A trophoblastic pseudotumor occurring in a young woman 6 months after a normal pregnancy is reported. Ultrastructural investigation demonstrated a close structural relationship between the infiltrating cells and those of the trophoblastic components of the normal human placenta, especially those seen in the primary villi of the developing placenta.", "contents": "Trophoblastic pseudotumor of the uterus: case report and ultrastructure. A trophoblastic pseudotumor occurring in a young woman 6 months after a normal pregnancy is reported. Ultrastructural investigation demonstrated a close structural relationship between the infiltrating cells and those of the trophoblastic components of the normal human placenta, especially those seen in the primary villi of the developing placenta."}
{"id": "PMID:221096", "title": "Sweat gland differentiation in mammary adenoid cystic carcinoma.", "content": "A breast tumor is described which presented as an exophytic mass, and which by both light and electron microscopic examination had a biphasic histologic composition. In the superficial area adjacent to the epidermis, it showed tubular differentiation similar to a cutaneous tubular apocrine adenoma and salivary basal cell adenoma, and, in the deeper portion, it had the characteristic features of adenoid cystic carcinoma. Their possible interrelationships are discussed, and mammary adenoid cystic carcinoma is briefly reviewed.", "contents": "Sweat gland differentiation in mammary adenoid cystic carcinoma. A breast tumor is described which presented as an exophytic mass, and which by both light and electron microscopic examination had a biphasic histologic composition. In the superficial area adjacent to the epidermis, it showed tubular differentiation similar to a cutaneous tubular apocrine adenoma and salivary basal cell adenoma, and, in the deeper portion, it had the characteristic features of adenoid cystic carcinoma. Their possible interrelationships are discussed, and mammary adenoid cystic carcinoma is briefly reviewed."}
{"id": "PMID:221097", "title": "Inflammatory fibrous histiocytoma in the left upper abdomen with a leukemoid blood picture.", "content": "A case of inflammatory fibrous histiocytoma arising in the left hypochondrium, which presented with a leukemoid reaction and was initially diagnosed as chronic neutrophilic leukemia, is described. The difficulty of interpreting the hematological findings, especially as the spleen appeared to be enlarged, is discussed. The tendency of this highly malignant group of tumors to cause a systemic granulocytosis is commented upon and attention is drawn to the lack of satisfactory treatment.", "contents": "Inflammatory fibrous histiocytoma in the left upper abdomen with a leukemoid blood picture. A case of inflammatory fibrous histiocytoma arising in the left hypochondrium, which presented with a leukemoid reaction and was initially diagnosed as chronic neutrophilic leukemia, is described. The difficulty of interpreting the hematological findings, especially as the spleen appeared to be enlarged, is discussed. The tendency of this highly malignant group of tumors to cause a systemic granulocytosis is commented upon and attention is drawn to the lack of satisfactory treatment."}
{"id": "PMID:221098", "title": "Food safety and public health: interaction of science and law in the federal regulatory process.", "content": "The programs of the Food and Drug Administration (FDA), which operates under a broad mandate of regulatory authority provided by the Congress in the form of the Food, Drug, and Cosmetic Act, demonstrate the way in which science and law interact to protect public health through the regulatory process. In particular, sections 402, 406, and 409 of the Act provide the means for regulating both new and old food products approved for use by the petition process as well as foods which present a potential hazard because of environmental accidents which result in residues of undesirable or dangerous chemical substances. The episodes of foods contaminated with polychlorinated biphenyls (PCBs) or polybrominated biphenyls (PBBs), and the manner in which action levels or guidelines were developed to regulate the allowable levels of these chemicals in foods, describe the pragmatic way in which FDA protects public health by restricting the allowable levels of chemical substances in foods.", "contents": "Food safety and public health: interaction of science and law in the federal regulatory process. The programs of the Food and Drug Administration (FDA), which operates under a broad mandate of regulatory authority provided by the Congress in the form of the Food, Drug, and Cosmetic Act, demonstrate the way in which science and law interact to protect public health through the regulatory process. In particular, sections 402, 406, and 409 of the Act provide the means for regulating both new and old food products approved for use by the petition process as well as foods which present a potential hazard because of environmental accidents which result in residues of undesirable or dangerous chemical substances. The episodes of foods contaminated with polychlorinated biphenyls (PCBs) or polybrominated biphenyls (PBBs), and the manner in which action levels or guidelines were developed to regulate the allowable levels of these chemicals in foods, describe the pragmatic way in which FDA protects public health by restricting the allowable levels of chemical substances in foods."}
{"id": "PMID:221099", "title": "Increased cyclic adenosine 3':5'-monophosphate phosphodiesterase activity in the epidermis of phorbol ester-treated mouse skin and in papillomas.", "content": "The potent tumor promoter, 12-O-tetradecanoylphorbol-13-acetate, produced a 2- to 3-fold increase in the activity of both the low- and high-affinity forms of cyclic adenosine 3':5'-monophosphate phosphodiesterase activity 13 hr after application to mouse skin. The magnitude of the enzyme induction correlated with the tumor-promoting activity of several doses of 12-O-tetradecanoylphorbol-13-acetate and of other phorbol esters. The induction of the low-affinity phosphodiesterase could be blocked by prior i.p. injection of the microtubule poisons, colchicine and vinblastine. The low-affinity cyclic adenosine 3':5'-monophosphate phosphodiesterase activity of the epidermal component of mouse skin papillomas produced by two-stage tumorigenesis was 3 times that of the surrounding uninvolved epidermis.", "contents": "Increased cyclic adenosine 3':5'-monophosphate phosphodiesterase activity in the epidermis of phorbol ester-treated mouse skin and in papillomas. The potent tumor promoter, 12-O-tetradecanoylphorbol-13-acetate, produced a 2- to 3-fold increase in the activity of both the low- and high-affinity forms of cyclic adenosine 3':5'-monophosphate phosphodiesterase activity 13 hr after application to mouse skin. The magnitude of the enzyme induction correlated with the tumor-promoting activity of several doses of 12-O-tetradecanoylphorbol-13-acetate and of other phorbol esters. The induction of the low-affinity phosphodiesterase could be blocked by prior i.p. injection of the microtubule poisons, colchicine and vinblastine. The low-affinity cyclic adenosine 3':5'-monophosphate phosphodiesterase activity of the epidermal component of mouse skin papillomas produced by two-stage tumorigenesis was 3 times that of the surrounding uninvolved epidermis."}
{"id": "PMID:221101", "title": "Reversal by glucocorticoid hormones of the loss of a fibronectin and probollagen matrix around transformed human cells.", "content": "Confluent cultured human skin fibroblasts had an extracellular fibrillar matrix of fibronectin and procollagen. Human skin fibroblasts transformed by SV40 did not have such a matrix. Treatment of transformed fibroblasts with 10(-5) to 10(-8) M dexamethasone and 10(-5) to 10(-7) M cortisol, but not testosterone or progesterone, caused partial restoration of the matrix. Glucocorticoid-treated transformed human fibroblasts can serve as a model for partial reversion toward normal or differentiation of transformed human fibroblasts.", "contents": "Reversal by glucocorticoid hormones of the loss of a fibronectin and probollagen matrix around transformed human cells. Confluent cultured human skin fibroblasts had an extracellular fibrillar matrix of fibronectin and procollagen. Human skin fibroblasts transformed by SV40 did not have such a matrix. Treatment of transformed fibroblasts with 10(-5) to 10(-8) M dexamethasone and 10(-5) to 10(-7) M cortisol, but not testosterone or progesterone, caused partial restoration of the matrix. Glucocorticoid-treated transformed human fibroblasts can serve as a model for partial reversion toward normal or differentiation of transformed human fibroblasts."}
{"id": "PMID:221102", "title": "Affinity cytotoxicity with an alcohol dehydrogenase-antibody conjugate and allyl alcohol.", "content": "A potent new enzyme-antibody conjugate system for amplifying cytotoxicity was tested in a well-defined model of hapten [2,4,6-trinitrophenyl (TNP)]-substituted tumor cells (HEp2) and purified anti-hapten antibody. Brief treatment of TNP-HEp2 cells with low concentrations (0.05 to 0.74 micrograms/ml) of antihapten antibody-alcohol dehydrogenase conjugate (Ab-ADH) followed by culture in complement-free medium containing nicotinamide adenine dinucleotide and allyl alcohol or 2-fluoroethanol resulted in 15 to 90% cell killing as measured by 5-[125l]iodo'-2-deoxyuridine uptake assay. The importance of the complete enzyme system was indicated by reduced or absent cytotoxicity if Ab-ADH, nicotinamide adenine dinucleotide, or allyl alcohol (or 2-fluorethanol) were omitted. Immunological specificity of the Ab-ADH was demonstrated by reduced or absent cytotoxicity when: (a) HEp2 cells were not coated with TNP; (b) Ab-ADH binding onto TNP-cells was blocked by free hapten (2,4-dinitrophenyllysine); or (c) unconjugated alcohol dehydrogenase and anti-TNP purified IgG anti-2,4,6-trinitrophenyl antibody with NAD+ and allyl alcohol or anti-TNP antibody with complement were used.", "contents": "Affinity cytotoxicity with an alcohol dehydrogenase-antibody conjugate and allyl alcohol. A potent new enzyme-antibody conjugate system for amplifying cytotoxicity was tested in a well-defined model of hapten [2,4,6-trinitrophenyl (TNP)]-substituted tumor cells (HEp2) and purified anti-hapten antibody. Brief treatment of TNP-HEp2 cells with low concentrations (0.05 to 0.74 micrograms/ml) of antihapten antibody-alcohol dehydrogenase conjugate (Ab-ADH) followed by culture in complement-free medium containing nicotinamide adenine dinucleotide and allyl alcohol or 2-fluoroethanol resulted in 15 to 90% cell killing as measured by 5-[125l]iodo'-2-deoxyuridine uptake assay. The importance of the complete enzyme system was indicated by reduced or absent cytotoxicity if Ab-ADH, nicotinamide adenine dinucleotide, or allyl alcohol (or 2-fluorethanol) were omitted. Immunological specificity of the Ab-ADH was demonstrated by reduced or absent cytotoxicity when: (a) HEp2 cells were not coated with TNP; (b) Ab-ADH binding onto TNP-cells was blocked by free hapten (2,4-dinitrophenyllysine); or (c) unconjugated alcohol dehydrogenase and anti-TNP purified IgG anti-2,4,6-trinitrophenyl antibody with NAD+ and allyl alcohol or anti-TNP antibody with complement were used."}
{"id": "PMID:221105", "title": "Localization of retinoic acid-binding protein in nuclei and the nuclear uptake of retinoic acid.", "content": "Retinoic acid-binding protein (RABP) has been detected in the nuclei of chick embryo skin and Lewis lung tumor. The nuclear binding component showed the same ligand specificity and sedimentation value as the cytosol RABP. Whereas pronase completely digested the nuclear binding component, DNase showed 40%, and RNase showed negligible digestive action. Retinoic acid binding to the nuclear RABP was completely inhibited by a mercurial, and the inhibition was reversed by dithiothreitol. The nonspecific uptake of retinoic acid by Lewis drug nuclei and chick embryo skin nuclei was inhibited up to 50% by cytosol RABP. The maximal inhibitory effect produced by cytosol RABP was after 45-min incubation. Incubation of Lewis lung tumor with [3H]retinoic acid resulted in the appearance of nuclear RABP: [3H]retinoic acid in the nuclei. The complex formed was weak, and most of the bound retinoic acid could be removed by dialysis.", "contents": "Localization of retinoic acid-binding protein in nuclei and the nuclear uptake of retinoic acid. Retinoic acid-binding protein (RABP) has been detected in the nuclei of chick embryo skin and Lewis lung tumor. The nuclear binding component showed the same ligand specificity and sedimentation value as the cytosol RABP. Whereas pronase completely digested the nuclear binding component, DNase showed 40%, and RNase showed negligible digestive action. Retinoic acid binding to the nuclear RABP was completely inhibited by a mercurial, and the inhibition was reversed by dithiothreitol. The nonspecific uptake of retinoic acid by Lewis drug nuclei and chick embryo skin nuclei was inhibited up to 50% by cytosol RABP. The maximal inhibitory effect produced by cytosol RABP was after 45-min incubation. Incubation of Lewis lung tumor with [3H]retinoic acid resulted in the appearance of nuclear RABP: [3H]retinoic acid in the nuclei. The complex formed was weak, and most of the bound retinoic acid could be removed by dialysis."}
{"id": "PMID:221106", "title": "Cyclic adenosine 3':5'-monophosphate and protein kinase activity in insulin-dependent and -independent mammary tumors.", "content": "Approximately 70% of primary 7,12-dimethylbenz(alpha)-anthracene-induced mammary tumors regressed when (tumor-bearing) rats were made diabetic after treatment with streptozotocin. In the intact animal, cyclic adenosine 3':5\"-monophosphate (cAMP) levels of tumors that regressed following the induction of diabetes were initially 4-fold lower than in unresponsive tumors but increased 4-fold during regression. The insulin-independent tumors showed no statistically significant changes. cAMP binding in cytosol of regressing tumors was about 80% above the initial values at 36 hr after therapy but decreased to about 45% 1 week later. On the contrary, the binding capacity of the nuclei showed a 56% increase at 36 hr and increased gradually to about 3-fold 1 week later. Within 36 hr after treatment, total histone kinase activity increased 127% in the cytosol and 153% in the nuclei of regressing tumors. The increment of histone kinase activity was almost totally in the cAMP-dependent component of the enzyme. These changes were not apparent in insulin-independent tumors. The results are interpreted to indicate that mammary tumor regression due to diabetes involves the cAMP system and occurs through a sequence of events similar to those observed during regression induced by either ovariectomy or dibutyryl cAMP (cyclic adenosine 3':5'-monophosphate) treatment.", "contents": "Cyclic adenosine 3':5'-monophosphate and protein kinase activity in insulin-dependent and -independent mammary tumors. Approximately 70% of primary 7,12-dimethylbenz(alpha)-anthracene-induced mammary tumors regressed when (tumor-bearing) rats were made diabetic after treatment with streptozotocin. In the intact animal, cyclic adenosine 3':5\"-monophosphate (cAMP) levels of tumors that regressed following the induction of diabetes were initially 4-fold lower than in unresponsive tumors but increased 4-fold during regression. The insulin-independent tumors showed no statistically significant changes. cAMP binding in cytosol of regressing tumors was about 80% above the initial values at 36 hr after therapy but decreased to about 45% 1 week later. On the contrary, the binding capacity of the nuclei showed a 56% increase at 36 hr and increased gradually to about 3-fold 1 week later. Within 36 hr after treatment, total histone kinase activity increased 127% in the cytosol and 153% in the nuclei of regressing tumors. The increment of histone kinase activity was almost totally in the cAMP-dependent component of the enzyme. These changes were not apparent in insulin-independent tumors. The results are interpreted to indicate that mammary tumor regression due to diabetes involves the cAMP system and occurs through a sequence of events similar to those observed during regression induced by either ovariectomy or dibutyryl cAMP (cyclic adenosine 3':5'-monophosphate) treatment."}
{"id": "PMID:221107", "title": "Effect of growth conditions on the content of the major groups of carbohydrates in chick embryo fibroblasts.", "content": "The levels of glycogen, hyaluronic acid, chondroitin sulfates, N-acetylneuraminic acid, all of the monosaccharide components of the glycoprotein and glycolipid fractions, and the monosaccharide pools were measured in cultured chick embryo fibroblasts. Under all growth conditions, the glycogen plus the glucose phosphate pool contained approximately 50% of total monosaccharide content of the cells. However, marked qualitative and quantitative alterations were found in the glycoprotein, glycolipid, and mucopolysaccharide fractions when growing cells reached confluence, when the growth temperature was shifted from 36 to 41 degrees, or when the cells were transformed with Rous sarcoma virus. From 65 to 95% of the total monosaccharide residues in these complex carbohydrates were found in the glycoprotein fraction, while the glycolipids contained only 5 to 10% of the residues, and the mucopolysaccharides contained 5 to 25%. Changes in the complex carbohydrates in normal cells following changes in cell density or growth temperature were so great that they obscured any transformation-dependent changes that might have occurred consistently in the virus-infected cells under different growth conditions.", "contents": "Effect of growth conditions on the content of the major groups of carbohydrates in chick embryo fibroblasts. The levels of glycogen, hyaluronic acid, chondroitin sulfates, N-acetylneuraminic acid, all of the monosaccharide components of the glycoprotein and glycolipid fractions, and the monosaccharide pools were measured in cultured chick embryo fibroblasts. Under all growth conditions, the glycogen plus the glucose phosphate pool contained approximately 50% of total monosaccharide content of the cells. However, marked qualitative and quantitative alterations were found in the glycoprotein, glycolipid, and mucopolysaccharide fractions when growing cells reached confluence, when the growth temperature was shifted from 36 to 41 degrees, or when the cells were transformed with Rous sarcoma virus. From 65 to 95% of the total monosaccharide residues in these complex carbohydrates were found in the glycoprotein fraction, while the glycolipids contained only 5 to 10% of the residues, and the mucopolysaccharides contained 5 to 25%. Changes in the complex carbohydrates in normal cells following changes in cell density or growth temperature were so great that they obscured any transformation-dependent changes that might have occurred consistently in the virus-infected cells under different growth conditions."}
{"id": "PMID:221108", "title": "Morphological and biochemical properties of a new human breast cancer cell line.", "content": "DU4475 is a new human breast cell line derived from a cutaneous metastatic nodule from a patient with advanced breast cancer. It has been in continuous culture for more than 1 year and has survived 140 subcultivations. The cells grow in suspension, displaying clusters and free-floating aggregates with serpentine-like outgrowths. The cell line is hypotetraploid with modal chromosome numbers between 86 and 93 and possesses five to six distinctive marker chromosomes. The cells grow readily in athymic nude mice and produce tumors from which cells can be reintroduced to culture in vitro.", "contents": "Morphological and biochemical properties of a new human breast cancer cell line. DU4475 is a new human breast cell line derived from a cutaneous metastatic nodule from a patient with advanced breast cancer. It has been in continuous culture for more than 1 year and has survived 140 subcultivations. The cells grow in suspension, displaying clusters and free-floating aggregates with serpentine-like outgrowths. The cell line is hypotetraploid with modal chromosome numbers between 86 and 93 and possesses five to six distinctive marker chromosomes. The cells grow readily in athymic nude mice and produce tumors from which cells can be reintroduced to culture in vitro."}
{"id": "PMID:221109", "title": "Delivery of essential services to alcoholics through the \"continuum of care\".", "content": "To provide for the delivery of essential and comprehensive services for alcoholics, a well-developed continuum of care encompasses the following services: an information and referral, or diagnostic, center; detoxification or receiving center; primary rehabilitation; extended rehabilitation; residential intermediate care; outpatient care; a family program; and an after-care program. All of these services are geared toward the ultimate goal of assisting the alcoholic to live independently in the community and to utilize a variety of positive coping devices while remaining abstinent from beverage alcohol.", "contents": "Delivery of essential services to alcoholics through the \"continuum of care\". To provide for the delivery of essential and comprehensive services for alcoholics, a well-developed continuum of care encompasses the following services: an information and referral, or diagnostic, center; detoxification or receiving center; primary rehabilitation; extended rehabilitation; residential intermediate care; outpatient care; a family program; and an after-care program. All of these services are geared toward the ultimate goal of assisting the alcoholic to live independently in the community and to utilize a variety of positive coping devices while remaining abstinent from beverage alcohol."}
{"id": "PMID:221111", "title": "Type C retrovirus activation and possible functions in the normal and tumor-bearing host.", "content": "The pathological consequences of tumor virus infection, transformation, and tumor development in certain experimental animals is a well-established and accepted fact. More recently, it has been suggested that these viruses may also have a physiological function participating in such processes as cellular differentiation, immune recognition, and embryogenesis. This paper delineates the current information giving some credence to physiological function for type C viruses.", "contents": "Type C retrovirus activation and possible functions in the normal and tumor-bearing host. The pathological consequences of tumor virus infection, transformation, and tumor development in certain experimental animals is a well-established and accepted fact. More recently, it has been suggested that these viruses may also have a physiological function participating in such processes as cellular differentiation, immune recognition, and embryogenesis. This paper delineates the current information giving some credence to physiological function for type C viruses."}
{"id": "PMID:221110", "title": "Alcohol-related diseases and carcinogenesis.", "content": "Possible mechanisms whereby alcohol abuse and alcohol-related diseases may promote the development of cancer are analyzed. The mechanisms discussed include: (a) contact-related local effects on the upper gastrointestinal tract; (b) the presence of low levels of carcinogens in alcoholic beverages; (c) induction of microsomal enzymes involved in carcinogen metabolism; (d) various types of cellular injury produced by ethanol and its metabolites and their relationship to cancer, particularly in the liver; (e) the nutritional disturbances frequently associated with alcohol abuse. The relationship between alcohol-induced cirrhosis and hepatocellular carcinoma is also discussed, and case histories of patients seen at the Bronx Veterans Administration Medical Center with hepatocellular carcinoma in the absence of cirrhosis are reviewed. Data are presented demonstrating the induction, by chronic ethanol consumption, of microsomal enzymes which convert procarcinogens to carcinogens. These data were derived from experiments in which the ability of microsomes isolated from liver, intestine, and lung tissues of ethanol-fed and control rats to activate several test carcinogens was examined in the Ames Salmonella-mutagenicity test. The hypothesis is presented that ethanol-mediated induction of enzyme systems which activate procarcinogens to carcinogens in various tissues contributes to the enhanced incidence of cancer in the alcoholic.", "contents": "Alcohol-related diseases and carcinogenesis. Possible mechanisms whereby alcohol abuse and alcohol-related diseases may promote the development of cancer are analyzed. The mechanisms discussed include: (a) contact-related local effects on the upper gastrointestinal tract; (b) the presence of low levels of carcinogens in alcoholic beverages; (c) induction of microsomal enzymes involved in carcinogen metabolism; (d) various types of cellular injury produced by ethanol and its metabolites and their relationship to cancer, particularly in the liver; (e) the nutritional disturbances frequently associated with alcohol abuse. The relationship between alcohol-induced cirrhosis and hepatocellular carcinoma is also discussed, and case histories of patients seen at the Bronx Veterans Administration Medical Center with hepatocellular carcinoma in the absence of cirrhosis are reviewed. Data are presented demonstrating the induction, by chronic ethanol consumption, of microsomal enzymes which convert procarcinogens to carcinogens. These data were derived from experiments in which the ability of microsomes isolated from liver, intestine, and lung tissues of ethanol-fed and control rats to activate several test carcinogens was examined in the Ames Salmonella-mutagenicity test. The hypothesis is presented that ethanol-mediated induction of enzyme systems which activate procarcinogens to carcinogens in various tissues contributes to the enhanced incidence of cancer in the alcoholic."}
{"id": "PMID:221112", "title": "Phase I and preliminary phase II study of neocarzinostatin.", "content": "Neocarzinostatin is a protein antitumor antibiotic isolated from cultures of Streptomyces carzinostaticus var.F41. The drug has undergone extensive clinical trial in Japan, and has been reported active against a variety of human tumors. A phase I and preliminary phase II evaluation of the drug has been performed, using an iv bolus daily x 5 schedule. Ninety-six patients have been treated at doses from 500 to 2250 units/m2/day. Courses were repeated at 4-week intervals if allowed by bone marrow recovery. Dose-limiting toxicity was myelosupppression, which occurred late (median nadir, Day 27). Myelosuppression was more pronounced in patients who had received previous chemotherapy. In nine patients (9%) thrombocytopenia was prolonged (greater than or equal to 45 days) or irreversible. Acute administration of the drug was associated with rigors in approximately half the patients. Gastrointestinal side effects were mild. Three patients had a severe acute reaction resembling anaphylaxis. The maximally tolerated dose for this dose schedule is approximately 2250 units/m2/day. Antitumor activity has been seen in hepatoma and hematologic malignancies. Activity in lung and colorectal carcinoma appears limited with this dose schedule.", "contents": "Phase I and preliminary phase II study of neocarzinostatin. Neocarzinostatin is a protein antitumor antibiotic isolated from cultures of Streptomyces carzinostaticus var.F41. The drug has undergone extensive clinical trial in Japan, and has been reported active against a variety of human tumors. A phase I and preliminary phase II evaluation of the drug has been performed, using an iv bolus daily x 5 schedule. Ninety-six patients have been treated at doses from 500 to 2250 units/m2/day. Courses were repeated at 4-week intervals if allowed by bone marrow recovery. Dose-limiting toxicity was myelosupppression, which occurred late (median nadir, Day 27). Myelosuppression was more pronounced in patients who had received previous chemotherapy. In nine patients (9%) thrombocytopenia was prolonged (greater than or equal to 45 days) or irreversible. Acute administration of the drug was associated with rigors in approximately half the patients. Gastrointestinal side effects were mild. Three patients had a severe acute reaction resembling anaphylaxis. The maximally tolerated dose for this dose schedule is approximately 2250 units/m2/day. Antitumor activity has been seen in hepatoma and hematologic malignancies. Activity in lung and colorectal carcinoma appears limited with this dose schedule."}
{"id": "PMID:221113", "title": "BCNU-5-fluorouracil combination therapy for recurrent malignant brain tumors.", "content": "Twenty-nine patients with recurrent malignant brain tumors were evaluated. BCNU (180 mg/m2) was administered iv on Day 1 and 5-fluorouracil (1 g/m2/day) was given by continuous infusion on Days 15--17. Courses were repeated every 6 weeks until tumor progression occurred. Before each course, a neurologic examination and radionuclide and computerized tomographic scans were performed. Response and progression were defined as improvement or deterioration, respectively, in at least two of the three tests. Nine of 29 patients (31%) responded to therapy, five of 29 (17%) showed progression, and 15 of 29 (52%) had disease stability. The estimated median time to progression was 27 weeks for all patients, 34 weeks for the response group, and 25 weeks for the stable group. Of all 29 patients, 24 (83%) had tumor progression arrested; 40% with response and 6% with stable disease were continuing therapy after 1 year. The stable disease group was larger and the duration of stability was longer than that seen in previous studies. Evaluated by time to progression, a BCNU-5-fluorouracil combination is superior to either BCNU alone or a BCNU-procarbazine combination.", "contents": "BCNU-5-fluorouracil combination therapy for recurrent malignant brain tumors. Twenty-nine patients with recurrent malignant brain tumors were evaluated. BCNU (180 mg/m2) was administered iv on Day 1 and 5-fluorouracil (1 g/m2/day) was given by continuous infusion on Days 15--17. Courses were repeated every 6 weeks until tumor progression occurred. Before each course, a neurologic examination and radionuclide and computerized tomographic scans were performed. Response and progression were defined as improvement or deterioration, respectively, in at least two of the three tests. Nine of 29 patients (31%) responded to therapy, five of 29 (17%) showed progression, and 15 of 29 (52%) had disease stability. The estimated median time to progression was 27 weeks for all patients, 34 weeks for the response group, and 25 weeks for the stable group. Of all 29 patients, 24 (83%) had tumor progression arrested; 40% with response and 6% with stable disease were continuing therapy after 1 year. The stable disease group was larger and the duration of stability was longer than that seen in previous studies. Evaluated by time to progression, a BCNU-5-fluorouracil combination is superior to either BCNU alone or a BCNU-procarbazine combination."}
{"id": "PMID:221114", "title": "Cyclic alternating combination chemotherapy for small cell bronchogenic carcinoma.", "content": "Sixty-one protocol-eligible patients with small cell bronchogenic carcinoma received cyclic alternating combination chemotherapy with two or three non-cross-resistant drug combinations. No chest or prophylactic brain radiation therapy was used. Twenty-eight months after starting treatment, disease-free survival was 23% for patients achieving a complete response (CR) and 13% overall. Initial treatment consisted of high-dose cyclophosphamide, methotrexate, and CCNU (CMC) for 6 weeks. Patients then received vincristine, adriamycin, and procarbazine (VAP) for 6 weeks. The addition of VAP increased the CR rate from 42% to 74% in limited-disease patients and from 24% to 36% in extensive-disease patients. Half of the patients were randomized to a third combination of VO-16-213 and ifosfamide. These patients were cycled at 6-week intervals through the three drug regimens while the remaining patients were cycled between CMC and VAP. The addition of VP-16-213 and ifosfamide did not increase the CR rate or prolong survival. Only complete responders survived beyond 24 months. Sequential use of non-cross-resistant drug combinations represents one method for increasing the CR rate.", "contents": "Cyclic alternating combination chemotherapy for small cell bronchogenic carcinoma. Sixty-one protocol-eligible patients with small cell bronchogenic carcinoma received cyclic alternating combination chemotherapy with two or three non-cross-resistant drug combinations. No chest or prophylactic brain radiation therapy was used. Twenty-eight months after starting treatment, disease-free survival was 23% for patients achieving a complete response (CR) and 13% overall. Initial treatment consisted of high-dose cyclophosphamide, methotrexate, and CCNU (CMC) for 6 weeks. Patients then received vincristine, adriamycin, and procarbazine (VAP) for 6 weeks. The addition of VAP increased the CR rate from 42% to 74% in limited-disease patients and from 24% to 36% in extensive-disease patients. Half of the patients were randomized to a third combination of VO-16-213 and ifosfamide. These patients were cycled at 6-week intervals through the three drug regimens while the remaining patients were cycled between CMC and VAP. The addition of VP-16-213 and ifosfamide did not increase the CR rate or prolong survival. Only complete responders survived beyond 24 months. Sequential use of non-cross-resistant drug combinations represents one method for increasing the CR rate."}
{"id": "PMID:221117", "title": "Intensive induction therapy for small cell carcinoma of the lung.", "content": "Fifteen patients with extensive small cell carcinoma of the lung and no prior therapy were treated with a chemotherapeutic regimen similar in intensity to the approach used in acute myelocytic leukemia. The patients received intensive induction therapy with cyclophosphamide, adriamycin, and VP-16-213 followed by treatment with a combination of BCNU, vincristine, methotrexate, and procarbazine. The objective response rate was 87% (13 of 15 patients) with three complete responses and ten partial responses. With the exception of one patient, the maximal response to therapy was achieved during therapy with the intensive cyclophosphamide, adriamycin, and VP-16-213 regimen. The three complete responders remain in remission for 159, 351, and 285 days but seven of the ten partial responders have relapsed and five of these have died. There was no unexpected morbidity associated with the intensive chemotherapy despite marked bone marrow suppression. This study demonstrates that very intensive combination chemotherapy can be safely used to achieve a high objective response rate in patients with extensive small cell carcinoma, but the complete response rate is low. An analysis of treatment failures and future directions is presented.", "contents": "Intensive induction therapy for small cell carcinoma of the lung. Fifteen patients with extensive small cell carcinoma of the lung and no prior therapy were treated with a chemotherapeutic regimen similar in intensity to the approach used in acute myelocytic leukemia. The patients received intensive induction therapy with cyclophosphamide, adriamycin, and VP-16-213 followed by treatment with a combination of BCNU, vincristine, methotrexate, and procarbazine. The objective response rate was 87% (13 of 15 patients) with three complete responses and ten partial responses. With the exception of one patient, the maximal response to therapy was achieved during therapy with the intensive cyclophosphamide, adriamycin, and VP-16-213 regimen. The three complete responders remain in remission for 159, 351, and 285 days but seven of the ten partial responders have relapsed and five of these have died. There was no unexpected morbidity associated with the intensive chemotherapy despite marked bone marrow suppression. This study demonstrates that very intensive combination chemotherapy can be safely used to achieve a high objective response rate in patients with extensive small cell carcinoma, but the complete response rate is low. An analysis of treatment failures and future directions is presented."}
{"id": "PMID:221120", "title": "In vitro growth of cutaneous T-cell lymphomas.", "content": "It is relatively easy to propagate EB virus-transformed normal and malignant B lymphocytes in vitro. Normal T lymphocytes divide for short periods of time after exposure to many mitogens. Exposure of normal T lymphocytes to lymphocyte-conditioned medium (LCM) permits them to divide for longer periods of time, but permanent cell lines cannot be established. Intial attempts to grow malignant T cells from patients with cutaneous T-cell lymphomas (CTCL) in unsupplemented growth medium resulted in the establishment of four EB virus-transformed B-lymphoblastoid lines. The responses of CTCL cells to mitogens and LCM varied from unresponsive to near normal. Subsequent attempts to grow CTCL cells in medium supplemented with mitogens or LCM resulted in the establishment of two cell lines lacking B-cell markers or EB virus. The cells of both lines initially had the ability to form E rosettes, although one of the lines has lost this ability with passage. The two lines can be distinguished from normal T cells by having some or all of the following properties: long-term proliferation, tumorigenecity in nude mice, gradual loss of dependence on mitogen or LCM, and convoluted nuclear morphology.", "contents": "In vitro growth of cutaneous T-cell lymphomas. It is relatively easy to propagate EB virus-transformed normal and malignant B lymphocytes in vitro. Normal T lymphocytes divide for short periods of time after exposure to many mitogens. Exposure of normal T lymphocytes to lymphocyte-conditioned medium (LCM) permits them to divide for longer periods of time, but permanent cell lines cannot be established. Intial attempts to grow malignant T cells from patients with cutaneous T-cell lymphomas (CTCL) in unsupplemented growth medium resulted in the establishment of four EB virus-transformed B-lymphoblastoid lines. The responses of CTCL cells to mitogens and LCM varied from unresponsive to near normal. Subsequent attempts to grow CTCL cells in medium supplemented with mitogens or LCM resulted in the establishment of two cell lines lacking B-cell markers or EB virus. The cells of both lines initially had the ability to form E rosettes, although one of the lines has lost this ability with passage. The two lines can be distinguished from normal T cells by having some or all of the following properties: long-term proliferation, tumorigenecity in nude mice, gradual loss of dependence on mitogen or LCM, and convoluted nuclear morphology."}
{"id": "PMID:221121", "title": "Effect of sodium loading and ACTH on blood pressure of sheep with reduced renal mass.", "content": "Sodium chloride loading produced a rise in blood pressure in intact sheep which was potentiated by reduction in renal mass. ACTH induced hypertension was also potentiated by reduced renal mass, suggesting a volume component for the hypertension when renal excretory capacity for salt and water is reduced.", "contents": "Effect of sodium loading and ACTH on blood pressure of sheep with reduced renal mass. Sodium chloride loading produced a rise in blood pressure in intact sheep which was potentiated by reduction in renal mass. ACTH induced hypertension was also potentiated by reduced renal mass, suggesting a volume component for the hypertension when renal excretory capacity for salt and water is reduced."}
{"id": "PMID:221125", "title": "Comparative studies of the physical state of the lipid phase of normal and hypercholesterolemic very low density lipoprotein.", "content": "Very low density lipoproteins (VLDL) were prepared from the serum of rabbits at various stages of hypercholesterolemia (95--1665 mg cholesterol/100 ml of serum). The most notable chemical change in hypercholesterolemic (hc) VLDL was the greatly increased content of cholesteryl esters and the greatly decreased content of triglycerides, compared to normal (n) VLDL. Structurally, the lipid region of n VLDL possessed a much lower microviscosity than did hc VLDL, when analyzed by fluorescence polarization and pyrene eximer methods. The microviscosity of the redispersed n VLDL lipid extract was considerably greater than the observed in n VLDL; but less than that of hc VLDL. Incorporation of pyrene into the lipid region of n VLDL and hc VLDL allowed assessment of various properties of the surface and hydrocarbon regions of these lipoproteins. Only slight differences were found in the pyrene monomer 3 : 1 fluorescence emission peak ratios, and in the rate constant for quenching of pyrene by O2. However, the quenching rate constant of pyrene by I- and iodoheptane were different for each lipoprotein.", "contents": "Comparative studies of the physical state of the lipid phase of normal and hypercholesterolemic very low density lipoprotein. Very low density lipoproteins (VLDL) were prepared from the serum of rabbits at various stages of hypercholesterolemia (95--1665 mg cholesterol/100 ml of serum). The most notable chemical change in hypercholesterolemic (hc) VLDL was the greatly increased content of cholesteryl esters and the greatly decreased content of triglycerides, compared to normal (n) VLDL. Structurally, the lipid region of n VLDL possessed a much lower microviscosity than did hc VLDL, when analyzed by fluorescence polarization and pyrene eximer methods. The microviscosity of the redispersed n VLDL lipid extract was considerably greater than the observed in n VLDL; but less than that of hc VLDL. Incorporation of pyrene into the lipid region of n VLDL and hc VLDL allowed assessment of various properties of the surface and hydrocarbon regions of these lipoproteins. Only slight differences were found in the pyrene monomer 3 : 1 fluorescence emission peak ratios, and in the rate constant for quenching of pyrene by O2. However, the quenching rate constant of pyrene by I- and iodoheptane were different for each lipoprotein."}
{"id": "PMID:221126", "title": "Heterotransplantation of human gastric cancer in nude mice.", "content": "Human gastric cancer was transplanted into the peritoneum of nude mice, and the progress of invasion and growth of cancer were investigated. Serial transplantations succeeded in 4 strains of human gastric cancer and one strain of canine gastric cancer induced by N-thyl-N-nitro-N-nitrosoguanidine (ENNG). The five strains grew subcutaneously in nude mice, and both single strain and mixed strain were transplanted into the mouse peritoneal cavity by a surgical procedure. In the single strain, cancer cells demonstrated mucosal and/or submucosal invasion in the gastrointestinal tract. In the mucosal layer, cancer permeation into the lymphatic duct was verified. In the histological examination, each strain of the mixed ones grew back to back with no interferance, showing front formation. The human strain and canine strain co-existed in the mouse. A human strain of poorly differentiated adenocarcinoma showed hematogenous metastasis to the liver. This is the first report that the invasion as one of biological characteristics of the primary human gastric cancer was clearly demonstrated, and also, another important biological characteristics i.e., the hematogenous liver metastasis was manifested in the mixed strain.", "contents": "Heterotransplantation of human gastric cancer in nude mice. Human gastric cancer was transplanted into the peritoneum of nude mice, and the progress of invasion and growth of cancer were investigated. Serial transplantations succeeded in 4 strains of human gastric cancer and one strain of canine gastric cancer induced by N-thyl-N-nitro-N-nitrosoguanidine (ENNG). The five strains grew subcutaneously in nude mice, and both single strain and mixed strain were transplanted into the mouse peritoneal cavity by a surgical procedure. In the single strain, cancer cells demonstrated mucosal and/or submucosal invasion in the gastrointestinal tract. In the mucosal layer, cancer permeation into the lymphatic duct was verified. In the histological examination, each strain of the mixed ones grew back to back with no interferance, showing front formation. The human strain and canine strain co-existed in the mouse. A human strain of poorly differentiated adenocarcinoma showed hematogenous metastasis to the liver. This is the first report that the invasion as one of biological characteristics of the primary human gastric cancer was clearly demonstrated, and also, another important biological characteristics i.e., the hematogenous liver metastasis was manifested in the mixed strain."}
{"id": "PMID:221127", "title": "Guanosine 3', 5'-cyclic monophosphate level in plasma of patients with cancer and various diseases.", "content": "Guanosine 3'5'-cyclic monophosphate (cGMP) in the plasma of normal persons and patients with lung or breast cancer and other kinds of neoplasma or other diseases was determined using radioimmunoassay. In comparison with normal persons, significant elevation occurred in the cGMP in the plasma of patients with various kinds of cancer or renal insufficiency. The average cGMP values in the plasma of eight normal persons, 16 patients with lung cancer, 16 patients with breast cancer, five patients with oesophagus cancer, three patients with liver cancer, three patients with stomach cancer, ten patients with renal insufficiency and two patients with myocardial infarction, were respectively 3.46, 9.05, 5.39, 5.42, 7.33, 11.66, 19.55, and 8.0 pmol per ml of plasma. There was no elevation in the cGMP in the plasma of the patients with other diseases studied.", "contents": "Guanosine 3', 5'-cyclic monophosphate level in plasma of patients with cancer and various diseases. Guanosine 3'5'-cyclic monophosphate (cGMP) in the plasma of normal persons and patients with lung or breast cancer and other kinds of neoplasma or other diseases was determined using radioimmunoassay. In comparison with normal persons, significant elevation occurred in the cGMP in the plasma of patients with various kinds of cancer or renal insufficiency. The average cGMP values in the plasma of eight normal persons, 16 patients with lung cancer, 16 patients with breast cancer, five patients with oesophagus cancer, three patients with liver cancer, three patients with stomach cancer, ten patients with renal insufficiency and two patients with myocardial infarction, were respectively 3.46, 9.05, 5.39, 5.42, 7.33, 11.66, 19.55, and 8.0 pmol per ml of plasma. There was no elevation in the cGMP in the plasma of the patients with other diseases studied."}
{"id": "PMID:221128", "title": "[Vitamin D3 sulfoconjugate distribution and evolution in pregnant or lactating rats].", "content": "24 hrs after intravenous injection of vitamin D3 35S sulfoconjugate the radioactivity in kidney is about twice as much in pregnant Rats as in lactating Rats. It decreases from 24 to 48 hrs in pregnant but increases in lactating Rats kidneys. Hydrolysis of vitamin 3H D3 sulfate is detected in kidney and liver extracts, the ratio of free vitamin D3 on vitamin D3 sulfate is higher in pregnant than in lactating animals. Mammary glands of lactating Rats contain mainly the unchanged vitamin D3 sulfate which can be hydrolysed by new born suckling pups.", "contents": "[Vitamin D3 sulfoconjugate distribution and evolution in pregnant or lactating rats]. 24 hrs after intravenous injection of vitamin D3 35S sulfoconjugate the radioactivity in kidney is about twice as much in pregnant Rats as in lactating Rats. It decreases from 24 to 48 hrs in pregnant but increases in lactating Rats kidneys. Hydrolysis of vitamin 3H D3 sulfate is detected in kidney and liver extracts, the ratio of free vitamin D3 on vitamin D3 sulfate is higher in pregnant than in lactating animals. Mammary glands of lactating Rats contain mainly the unchanged vitamin D3 sulfate which can be hydrolysed by new born suckling pups."}
{"id": "PMID:221131", "title": "Dissociation between the electrophysiological properties and total tissue cyclic guanosine monophosphate content of guinea pig atria.", "content": "The purpose of this study was to investigate the role of cyclic guanosine monophosphate (cyclic GMP) in mediating the direct electrophysiological effects of acetylcholine in guinea pig atria. Acetylcholine significantly diminished spontaneous rate of right atria without increasing cyclic GMP content. Reductions in rate following acetylcholine were augmented by pretreatment with physostigmine, but cyclic GMP levels remained unchanged. In left atria, acetylcholine significantly shortened action potential duration within 5 seconds (both with and without physostigmine pretreatment), but cyclic GMP content was not significantly elevated. Cyclic GMP levels in right atria were significantly increased in response to acetylcholine when the Ca2+ content of the buffer was elevated from 1.25 mM TO 2.5 MM; however, reductions in automaticity in the right atria were not augmented in the high Ca2+ buffer. Marked increases in cyclic GMP content were produced by Na nitroprusside superfusion without changing automaticity of right atria or action potential duration of left atria. Finally, both right and left atria were superfused with cyclic GMP analogs (8-bromo cyclic GMP and dibutyryl cyclic GMP) at high concentrations (10(-4)) for 15 minutes without producing significant effects on spontaneous rate or action potential duration. These results failed to show a correlation between total tissue cyclic GMP content and the electrophysiological effects of acetylcholine on guinea pig atria. The reasons for this are either that cyclic GMP does not mediate directly the electrophysiological effects of acetylcholine, or that small changes in cyclic GMP concentrations, undetectable when total tissue nucleotide levels are measured, occur in discrete effector pools of the cardiac cell to mediate the intracellular effects of the choline ester.", "contents": "Dissociation between the electrophysiological properties and total tissue cyclic guanosine monophosphate content of guinea pig atria. The purpose of this study was to investigate the role of cyclic guanosine monophosphate (cyclic GMP) in mediating the direct electrophysiological effects of acetylcholine in guinea pig atria. Acetylcholine significantly diminished spontaneous rate of right atria without increasing cyclic GMP content. Reductions in rate following acetylcholine were augmented by pretreatment with physostigmine, but cyclic GMP levels remained unchanged. In left atria, acetylcholine significantly shortened action potential duration within 5 seconds (both with and without physostigmine pretreatment), but cyclic GMP content was not significantly elevated. Cyclic GMP levels in right atria were significantly increased in response to acetylcholine when the Ca2+ content of the buffer was elevated from 1.25 mM TO 2.5 MM; however, reductions in automaticity in the right atria were not augmented in the high Ca2+ buffer. Marked increases in cyclic GMP content were produced by Na nitroprusside superfusion without changing automaticity of right atria or action potential duration of left atria. Finally, both right and left atria were superfused with cyclic GMP analogs (8-bromo cyclic GMP and dibutyryl cyclic GMP) at high concentrations (10(-4)) for 15 minutes without producing significant effects on spontaneous rate or action potential duration. These results failed to show a correlation between total tissue cyclic GMP content and the electrophysiological effects of acetylcholine on guinea pig atria. The reasons for this are either that cyclic GMP does not mediate directly the electrophysiological effects of acetylcholine, or that small changes in cyclic GMP concentrations, undetectable when total tissue nucleotide levels are measured, occur in discrete effector pools of the cardiac cell to mediate the intracellular effects of the choline ester."}
{"id": "PMID:221133", "title": "The combined effect of smoking and coffee drinking on LDL and HDL cholesterol.", "content": "Conflicting reports on the effect of smoking and coffee drinking on lipoproteins prompted us to study the combined effect of these two associated, widely prevalent habits in 361 persons randomly sampled from the Evans County cohort. Low-density lipoprotein (LDL) cholesterol levels were significantly higher among persons who smoked cigarettes and consumed five or more cups of coffee per day than among nonsmokers who abstained from coffee. Conversely, high-density lipoprotein (HDL) cholesterol was higher in persons who did not smoke or drink coffee than in coffee-consuming smokers. However, this trend was not statistically significant. Triglycerides and very low-density lipoprotein (VLDL) cholesterol were highest among smokers who drank five or more cups of coffee per day, but these differences did not reach statistical significance. Lipoprotein cholesterol levels were adjusted for age, sex and body mass. Smoking and coffee drinking interact in affecting LDL and total cholesterol, but coffee drinking alone did not appear to affect blood lipids.", "contents": "The combined effect of smoking and coffee drinking on LDL and HDL cholesterol. Conflicting reports on the effect of smoking and coffee drinking on lipoproteins prompted us to study the combined effect of these two associated, widely prevalent habits in 361 persons randomly sampled from the Evans County cohort. Low-density lipoprotein (LDL) cholesterol levels were significantly higher among persons who smoked cigarettes and consumed five or more cups of coffee per day than among nonsmokers who abstained from coffee. Conversely, high-density lipoprotein (HDL) cholesterol was higher in persons who did not smoke or drink coffee than in coffee-consuming smokers. However, this trend was not statistically significant. Triglycerides and very low-density lipoprotein (VLDL) cholesterol were highest among smokers who drank five or more cups of coffee per day, but these differences did not reach statistical significance. Lipoprotein cholesterol levels were adjusted for age, sex and body mass. Smoking and coffee drinking interact in affecting LDL and total cholesterol, but coffee drinking alone did not appear to affect blood lipids."}
{"id": "PMID:221134", "title": "Protection of mitochondrial function during ischemia by potassium cardioplegia: correlation with ischemic contracture.", "content": "The effect of potassium cardioplegia on mitochondrial function was evaluated in the ischemic isolated rat heart. Mitochondrial function as well as adenosine triphosphate (ATP) levels were determined at the initiation of ischemic contracture, at the completion of ischemic contracture, and 20 minutes following contracture completion. Group I received no cardioplegia prior to ischemia, while Group II received potassium cardioplegia prior to the onset of ischemia. The respiratory control index (RCI), which is the primary measure of the intactness of mitochondrial function, was calculated with both a NAD (nicotinamide adenine dinucleotide)-linked substrate and a FAD (flavin adenine dinucleotide)-linked substrate. Potassium cardioplegia significantly delayed ischemic contracture initiation and completion. Although the RCI and ATP levels decreased significantly at successive levels of contracture, there was no difference in the RCI or ATP content between Group I and Group II at contracture initiation or completion. Unlike previous investigations that have used a time-base to examine mitochondrial function and acute cardiac ischemic injury, we correlated mitochondrial function with the measurable physiologic event ischemic contracture. The data indicated that potassium cardioplegia preserved ATP content and mitochondrial function, and that contracture initiation and completion correlate well with specific ATP levels and mitochondrial respiratory control. The relationship between mitochondrial function and ATP content indicates that the beneficial effect of potassium cardioplegia on mitochondrial function may be secondary to the preservation of high-energy phosphate levels which provide energy for mitochondrial maintenance.", "contents": "Protection of mitochondrial function during ischemia by potassium cardioplegia: correlation with ischemic contracture. The effect of potassium cardioplegia on mitochondrial function was evaluated in the ischemic isolated rat heart. Mitochondrial function as well as adenosine triphosphate (ATP) levels were determined at the initiation of ischemic contracture, at the completion of ischemic contracture, and 20 minutes following contracture completion. Group I received no cardioplegia prior to ischemia, while Group II received potassium cardioplegia prior to the onset of ischemia. The respiratory control index (RCI), which is the primary measure of the intactness of mitochondrial function, was calculated with both a NAD (nicotinamide adenine dinucleotide)-linked substrate and a FAD (flavin adenine dinucleotide)-linked substrate. Potassium cardioplegia significantly delayed ischemic contracture initiation and completion. Although the RCI and ATP levels decreased significantly at successive levels of contracture, there was no difference in the RCI or ATP content between Group I and Group II at contracture initiation or completion. Unlike previous investigations that have used a time-base to examine mitochondrial function and acute cardiac ischemic injury, we correlated mitochondrial function with the measurable physiologic event ischemic contracture. The data indicated that potassium cardioplegia preserved ATP content and mitochondrial function, and that contracture initiation and completion correlate well with specific ATP levels and mitochondrial respiratory control. The relationship between mitochondrial function and ATP content indicates that the beneficial effect of potassium cardioplegia on mitochondrial function may be secondary to the preservation of high-energy phosphate levels which provide energy for mitochondrial maintenance."}
{"id": "PMID:221135", "title": "A comparison of angiotensinase and placental leucine aminopeptidase during normal pregnancy.", "content": "1. Serum leucine aminopeptidase activity measured by its action on hydrolysis of L-leucyl-beta-naphthylamide was increased progressively as pregnancy advanced. Angiotensinase activity determined by bioasaay showed parallel increase during normal pregnancy. 2. The effects of heat treatment and L-methionine on the activity of angiotensinase were compared with those on leucine aminopeptidase activity in pregnancy serum.", "contents": "A comparison of angiotensinase and placental leucine aminopeptidase during normal pregnancy. 1. Serum leucine aminopeptidase activity measured by its action on hydrolysis of L-leucyl-beta-naphthylamide was increased progressively as pregnancy advanced. Angiotensinase activity determined by bioasaay showed parallel increase during normal pregnancy. 2. The effects of heat treatment and L-methionine on the activity of angiotensinase were compared with those on leucine aminopeptidase activity in pregnancy serum."}
{"id": "PMID:221136", "title": "Clinical biochemistry of epilepsy. I. Nature of the disease and a review of the chemical findings in epilepsy.", "content": "In idiopathic or generalized epilepsy, serum glucose and cholesterol concentrations tend to be low, especially just before the seizure. Glucose tolerance curves are abnormal and variable. The electrolyte balance is disturbed, and epileptics tend to go readily into alkalosis. Serum [Na+] is usually unaffected, but [K+] is normal to low between attacks and increases during and after the seizure. Serum [Cl-] is usually high just before the seizure. Epileptics are generally mildly hypocalcemic, especially in the period before the seizure. Serum urea and nonprotein nitrogen values are low between paroxysms but increase after the seizure. Serum protein concentration is usually normal. Stress, which releases epinephrine and corticotropin, results in high serum citrate concentration, which probably contributes to decreased serum [Ca2+] just before a seizure. In the healthy individual, any increase in serum citrate is accompanied by increasing [Ca2+]. In the rabbit, convulsions can be induced with corticotropin, a result of increased serum citrate concentration coupled with a decrease in [Ca2+]. The net result is severe hypo-ionic-calcemia. A similar phenomenon has been reported in a few humans. Administration of insulin causes serum citrate concentrations to decrease. Apparently, the dynamic system that controls glucose and lipid metabolism, and thus electrolyte balance, through the hormones epinephrine, corticotropin, insulin, glucagon, calcitonin, and parathormone, is abnormal in the epileptic.", "contents": "Clinical biochemistry of epilepsy. I. Nature of the disease and a review of the chemical findings in epilepsy. In idiopathic or generalized epilepsy, serum glucose and cholesterol concentrations tend to be low, especially just before the seizure. Glucose tolerance curves are abnormal and variable. The electrolyte balance is disturbed, and epileptics tend to go readily into alkalosis. Serum [Na+] is usually unaffected, but [K+] is normal to low between attacks and increases during and after the seizure. Serum [Cl-] is usually high just before the seizure. Epileptics are generally mildly hypocalcemic, especially in the period before the seizure. Serum urea and nonprotein nitrogen values are low between paroxysms but increase after the seizure. Serum protein concentration is usually normal. Stress, which releases epinephrine and corticotropin, results in high serum citrate concentration, which probably contributes to decreased serum [Ca2+] just before a seizure. In the healthy individual, any increase in serum citrate is accompanied by increasing [Ca2+]. In the rabbit, convulsions can be induced with corticotropin, a result of increased serum citrate concentration coupled with a decrease in [Ca2+]. The net result is severe hypo-ionic-calcemia. A similar phenomenon has been reported in a few humans. Administration of insulin causes serum citrate concentrations to decrease. Apparently, the dynamic system that controls glucose and lipid metabolism, and thus electrolyte balance, through the hormones epinephrine, corticotropin, insulin, glucagon, calcitonin, and parathormone, is abnormal in the epileptic."}
{"id": "PMID:221137", "title": "Clinical biochemistry of epilepsy. II. Observations on two types of epileptiform convulsions induced in rabbits with corticotropin.", "content": "We propose than an alarm mechanism is operative in animals, designed to regulate neuromuscular irritability by regulating [Ca2+]. Epinephrine or corticotropin (ACTH), injected intramuscularly into animals, causes a hypercitricemia, resulting in decreased [Ca2+]. This increases muscular excitability to facilitate escape. To avoid over reaction, [Cl-] is shifted into the plasma without a concomitant shift of Na+, thus generating an acidosis and an increase in ionization of Ca. Plasma pH, pCO2, total CO2, and [K+] decrease, and [Mg2+] increases. The acidosis, decrease in K+, and increase in [Mg2+] serve to counteract the effect of the decrease in [Ca2+], to protect against tetany. In the rabbit the hypercitricemia observed upon ACTH administration is accompained by a severe hypocalcemia and drop in blood pressure, resluting in tetanic convulsions. This seems to indicate calcitonin release, independent of the hypercitricemia. Thyroidectomized rabbits show only mild hypocalcemia when given ACTH, but develop a severe acidosis and typical grand mal epileptiform seizures. Administration of ACTH and then calcitonin to the goat, an animal resistant to the effects of ACTH alone, simulates the effect observed in the rabbit with respect to changes in blood components and blood pressure. Changes in the blood in the goat and rabbit resemble those in humans before an epileptic seizure. alpha-Melanotropin, containing a portion of the ACTH sequence, reacts in a manner similar to ACTH but more rapidly.", "contents": "Clinical biochemistry of epilepsy. II. Observations on two types of epileptiform convulsions induced in rabbits with corticotropin. We propose than an alarm mechanism is operative in animals, designed to regulate neuromuscular irritability by regulating [Ca2+]. Epinephrine or corticotropin (ACTH), injected intramuscularly into animals, causes a hypercitricemia, resulting in decreased [Ca2+]. This increases muscular excitability to facilitate escape. To avoid over reaction, [Cl-] is shifted into the plasma without a concomitant shift of Na+, thus generating an acidosis and an increase in ionization of Ca. Plasma pH, pCO2, total CO2, and [K+] decrease, and [Mg2+] increases. The acidosis, decrease in K+, and increase in [Mg2+] serve to counteract the effect of the decrease in [Ca2+], to protect against tetany. In the rabbit the hypercitricemia observed upon ACTH administration is accompained by a severe hypocalcemia and drop in blood pressure, resluting in tetanic convulsions. This seems to indicate calcitonin release, independent of the hypercitricemia. Thyroidectomized rabbits show only mild hypocalcemia when given ACTH, but develop a severe acidosis and typical grand mal epileptiform seizures. Administration of ACTH and then calcitonin to the goat, an animal resistant to the effects of ACTH alone, simulates the effect observed in the rabbit with respect to changes in blood components and blood pressure. Changes in the blood in the goat and rabbit resemble those in humans before an epileptic seizure. alpha-Melanotropin, containing a portion of the ACTH sequence, reacts in a manner similar to ACTH but more rapidly."}
{"id": "PMID:221138", "title": "Factors affecting the concentration of triacylglycerols (triglycerides in plasma: reference values for adults.", "content": "We studied factors influencing concentrations of triglycerides in the blood of a presumably healthy population of about 9000 persons. Using multi-dimensional analysis, we show, in addition to various related to sex and age, the relation between triglycerides and uric acid, overweight, arterial blood pressure, use of oral contraceptives (in women), consumption of alcohol and tobacco, and lack of physical exercise. These factors were classified as a function of their discriminative power by the statistical method of segmentation. We thus chose the following factors as criteria for exclusion from a reference population for the values of triglycerides in blood: in men 20 to 39 years old, overweight more than 90%; in men 40 to 59 years old, overweight of more than 115%, consumption of more than half a liter of wine per day or of more than 11 cigarettes, use of medicines, and a blood uric acid exceeding 420 mumol/L; in women 20 to 39 years old, contraceptives and overweight; in women 40 to 59 years old, overweight or more than 130% and the intake of medicines. At the 97.5th percentile of the reference population as compared with a non-selected population, the values were 80% less for men 20 to 39 years old, 95% less for men 40 to 59 years old, and only 26 to 30% less for women 20 to 59 years old.", "contents": "Factors affecting the concentration of triacylglycerols (triglycerides in plasma: reference values for adults. We studied factors influencing concentrations of triglycerides in the blood of a presumably healthy population of about 9000 persons. Using multi-dimensional analysis, we show, in addition to various related to sex and age, the relation between triglycerides and uric acid, overweight, arterial blood pressure, use of oral contraceptives (in women), consumption of alcohol and tobacco, and lack of physical exercise. These factors were classified as a function of their discriminative power by the statistical method of segmentation. We thus chose the following factors as criteria for exclusion from a reference population for the values of triglycerides in blood: in men 20 to 39 years old, overweight more than 90%; in men 40 to 59 years old, overweight of more than 115%, consumption of more than half a liter of wine per day or of more than 11 cigarettes, use of medicines, and a blood uric acid exceeding 420 mumol/L; in women 20 to 39 years old, contraceptives and overweight; in women 40 to 59 years old, overweight or more than 130% and the intake of medicines. At the 97.5th percentile of the reference population as compared with a non-selected population, the values were 80% less for men 20 to 39 years old, 95% less for men 40 to 59 years old, and only 26 to 30% less for women 20 to 59 years old."}
{"id": "PMID:221139", "title": "Determination of high-density lipoproteins: screening methods compared.", "content": "Factors reflecting the concentration of high-density lipoproteins in serum were assessed for 108 men and 106 women participating in a Venetian screening program for hyperlipoproteinemia. The methods applied, optimized in our laboratory, were: (a) cholesterol in high-density lipoproteins, determined in the supernate after sedimentation of the very-low-density lipoproteins + low-density lipoproteins with dextran sulfate or sodium phosphotungstate; and (b) immunochemical quantitation of apolipoprotein A-I and apolipoprotein A-II by Laurell's \"rocket\" technique. The latter determinations were performed with total serum before and after delipidation with diispropyl ether/n-butanol (6/4 by vol). The dextran sulfate method gave about 5% higher values than did the phosphotungstate method, but the correlation between the two was excellent (r = 0.95). Results of the immunochemical quantitation indicate that delipidation of lipoproteins before Laurell electrophoresis may not be necessary if only freshly drawn sera are used.", "contents": "Determination of high-density lipoproteins: screening methods compared. Factors reflecting the concentration of high-density lipoproteins in serum were assessed for 108 men and 106 women participating in a Venetian screening program for hyperlipoproteinemia. The methods applied, optimized in our laboratory, were: (a) cholesterol in high-density lipoproteins, determined in the supernate after sedimentation of the very-low-density lipoproteins + low-density lipoproteins with dextran sulfate or sodium phosphotungstate; and (b) immunochemical quantitation of apolipoprotein A-I and apolipoprotein A-II by Laurell's \"rocket\" technique. The latter determinations were performed with total serum before and after delipidation with diispropyl ether/n-butanol (6/4 by vol). The dextran sulfate method gave about 5% higher values than did the phosphotungstate method, but the correlation between the two was excellent (r = 0.95). Results of the immunochemical quantitation indicate that delipidation of lipoproteins before Laurell electrophoresis may not be necessary if only freshly drawn sera are used."}
{"id": "PMID:221140", "title": "The use of the electroencephalogram in patients admitted for alcohol abuse with seizures.", "content": "This study of 174 seizure presenting alcohol abusers revealed that the EEG is overwhelmingly normal by visual inspection. When the EEG is abnormal, however, usefulness is significant. The probable EEG findings in this group are presented and discussed here both clinically and experimentally. The literature is reviewed and while much divergent opinion is revealed, it basically is in agreement with the conclusion as set forth under E, significant findings.", "contents": "The use of the electroencephalogram in patients admitted for alcohol abuse with seizures. This study of 174 seizure presenting alcohol abusers revealed that the EEG is overwhelmingly normal by visual inspection. When the EEG is abnormal, however, usefulness is significant. The probable EEG findings in this group are presented and discussed here both clinically and experimentally. The literature is reviewed and while much divergent opinion is revealed, it basically is in agreement with the conclusion as set forth under E, significant findings."}
{"id": "PMID:221143", "title": "Regression of multiple osseous metastatic renal cell carcinoma.", "content": "A 65-year-old man with 6 osseous metastatic lesions was successfully treated by nephrectomy. Five of 6 metastatic tumors, 2 of which were histologically proved, dramatically regressed and disappeared roentgenographically. The other metastasis was removed by amputation 4 years prior to the nephrectomy. No apparent complication was found after the nephrectomy and the patient is in very good health. The factors responsible for regression of osseous metastatic renal cell carcinoma cannot be fully explained. The only common treatment given to 4 patients whose osseous renal cell cancer regressed, was nephrectomy. Since every therapy for metastatic renal cell cancer is unreliable, palliative nephrectomy seems to be justified as a treatment of choice even when osseous metastases are noted and there is a possibility of regression of metastatic lesions. Regression of osseous metastasis from renal cell carcinoma is extremely rare and only 3 cases have been reported.", "contents": "Regression of multiple osseous metastatic renal cell carcinoma. A 65-year-old man with 6 osseous metastatic lesions was successfully treated by nephrectomy. Five of 6 metastatic tumors, 2 of which were histologically proved, dramatically regressed and disappeared roentgenographically. The other metastasis was removed by amputation 4 years prior to the nephrectomy. No apparent complication was found after the nephrectomy and the patient is in very good health. The factors responsible for regression of osseous metastatic renal cell carcinoma cannot be fully explained. The only common treatment given to 4 patients whose osseous renal cell cancer regressed, was nephrectomy. Since every therapy for metastatic renal cell cancer is unreliable, palliative nephrectomy seems to be justified as a treatment of choice even when osseous metastases are noted and there is a possibility of regression of metastatic lesions. Regression of osseous metastasis from renal cell carcinoma is extremely rare and only 3 cases have been reported."}
{"id": "PMID:221150", "title": "Adenosine 3',5'-cyclic monophosphate levels in normal and IAA-induced tumours in bean (Phaseolus vulgaris L.) embryos.", "content": "Endogenous levels of adenosine 3',5'-cyclic monophosphate in indole-3-acetic acid induced tumours, and control bean embryos were measured with Gilman protein binding assay. No significant differences in cAMP concentrations were found in IAA-induced tumours, which suggests that IAA does not mediate cAMP synthesis in bean embryos.", "contents": "Adenosine 3',5'-cyclic monophosphate levels in normal and IAA-induced tumours in bean (Phaseolus vulgaris L.) embryos. Endogenous levels of adenosine 3',5'-cyclic monophosphate in indole-3-acetic acid induced tumours, and control bean embryos were measured with Gilman protein binding assay. No significant differences in cAMP concentrations were found in IAA-induced tumours, which suggests that IAA does not mediate cAMP synthesis in bean embryos."}
{"id": "PMID:221151", "title": "Chromosome breakage and xenotropic C-type virus in embryonic cultures from New Zealand black mice.", "content": "A considerable increase in chromatid and chromosome breaks, as well as excessive fragmentation and \"pulverization\" of whole metaphase plates was observed in embryonic fibroblast cultures from New Zealand black mice. A C-type RNA virus with a xenotropic host range was isolated from the supernatant fluid of co-cultures of NZB cells and heterologous permissive cells (SIRC cell line). One of the NZB cultures produced this virus without amplification by co-cultivation after spontaneous transformation of the cells. NZB cells are supposed to lack normal restriction of complete xenotropic virus expression and to release this endogenous virus spontaneously at a high level. It is hypothesized that the excessive chromosome damage observed in these cell cultures is related to the permanent production of virus, thus indicating a chromosome breaking effect of endogenous viruses.", "contents": "Chromosome breakage and xenotropic C-type virus in embryonic cultures from New Zealand black mice. A considerable increase in chromatid and chromosome breaks, as well as excessive fragmentation and \"pulverization\" of whole metaphase plates was observed in embryonic fibroblast cultures from New Zealand black mice. A C-type RNA virus with a xenotropic host range was isolated from the supernatant fluid of co-cultures of NZB cells and heterologous permissive cells (SIRC cell line). One of the NZB cultures produced this virus without amplification by co-cultivation after spontaneous transformation of the cells. NZB cells are supposed to lack normal restriction of complete xenotropic virus expression and to release this endogenous virus spontaneously at a high level. It is hypothesized that the excessive chromosome damage observed in these cell cultures is related to the permanent production of virus, thus indicating a chromosome breaking effect of endogenous viruses."}
{"id": "PMID:221152", "title": "Hypersomnolent and nonhypersomnolent patients with upper airway obstruction during sleep.", "content": "When the syndrome consisting of sleep-induced apnea and hypersomnolence is due to upper airway obstruction, the hypersomnolence is believed to be the direct result of deprivation of sleep related to such obstructions. The purpose of this report is to describe a group of four asymptomatic subjects with upper airway obstruction during sleep. These subjects were matched with a group of patients with the syndrome of sleep-induced apnea and hypersomnolence. There were no significant differences between symptomatic and asymptomatic groups in terms of the absolute number of upper airway obstructions (252 vs 231), their mean duration (20.8 vs 25.9 seconds), the mean arterial carbon dioxide tension during sleep (39 vs 39 mm Hg), or the electroencephalographic patterns during sleep. The only variables that emerged as significantly different between the two groups were the weights (128 vs 90 kg; P less than 0.05), the low arterial oxygen pressure (PaO2) on waking (54 vs 80 mm Hg; P less than 0.002), and the lower PaO2 during sleep (47 vs 70 mm Hg; P less than 0.01) in the symptomatic patients. From these data, we conclude that the hypersomnolence in patients with sleep-induced apnea due to upper airway obstruction cannot be explained by deprivation of sleep, and other factors need to be carefully examined in future studies.", "contents": "Hypersomnolent and nonhypersomnolent patients with upper airway obstruction during sleep. When the syndrome consisting of sleep-induced apnea and hypersomnolence is due to upper airway obstruction, the hypersomnolence is believed to be the direct result of deprivation of sleep related to such obstructions. The purpose of this report is to describe a group of four asymptomatic subjects with upper airway obstruction during sleep. These subjects were matched with a group of patients with the syndrome of sleep-induced apnea and hypersomnolence. There were no significant differences between symptomatic and asymptomatic groups in terms of the absolute number of upper airway obstructions (252 vs 231), their mean duration (20.8 vs 25.9 seconds), the mean arterial carbon dioxide tension during sleep (39 vs 39 mm Hg), or the electroencephalographic patterns during sleep. The only variables that emerged as significantly different between the two groups were the weights (128 vs 90 kg; P less than 0.05), the low arterial oxygen pressure (PaO2) on waking (54 vs 80 mm Hg; P less than 0.002), and the lower PaO2 during sleep (47 vs 70 mm Hg; P less than 0.01) in the symptomatic patients. From these data, we conclude that the hypersomnolence in patients with sleep-induced apnea due to upper airway obstruction cannot be explained by deprivation of sleep, and other factors need to be carefully examined in future studies."}
{"id": "PMID:221153", "title": "Biopsy of the main carina; staging lung cancer with the fiberoptic bronchoscope.", "content": "The efficacy of main carinal biopsy through the fiberoptic bronchoscope for evaluating resectability has not been determined. Forty-eight patients with carcinoma, but without gross neoplastic involvement of the main carina, underwent biopsy. Five (10 percent) had abnormal results on biopsy of the main carina. Three of the five patients were initially considered candidates for surgery. There were no complications from the procedure. Biopsy of the main carina through the fiberoptic bronchoscope is a valuable staging procedure in selected patients because of its simplicity and yield and the significance of abnormal findings.", "contents": "Biopsy of the main carina; staging lung cancer with the fiberoptic bronchoscope. The efficacy of main carinal biopsy through the fiberoptic bronchoscope for evaluating resectability has not been determined. Forty-eight patients with carcinoma, but without gross neoplastic involvement of the main carina, underwent biopsy. Five (10 percent) had abnormal results on biopsy of the main carina. Three of the five patients were initially considered candidates for surgery. There were no complications from the procedure. Biopsy of the main carina through the fiberoptic bronchoscope is a valuable staging procedure in selected patients because of its simplicity and yield and the significance of abnormal findings."}
{"id": "PMID:221155", "title": "Disseminated aspergillosis, Cushing's syndrome, and oat cell carcinoma of the lung.", "content": "Disseminated aspergillosis is a known complication of neoplastic disease; however, it is usually associated with neoplasms of the hematopoietic or lymphoreticular systems or with immunosuppressed states. We describe the previously unreported association of disseminated aspergillosis and Cushing's syndrome secondary to a corticotropin-secreting oat cell carcinoma of the lung, and we review the current literature on disseminated aspergillosis complicating neoplastic disease.", "contents": "Disseminated aspergillosis, Cushing's syndrome, and oat cell carcinoma of the lung. Disseminated aspergillosis is a known complication of neoplastic disease; however, it is usually associated with neoplasms of the hematopoietic or lymphoreticular systems or with immunosuppressed states. We describe the previously unreported association of disseminated aspergillosis and Cushing's syndrome secondary to a corticotropin-secreting oat cell carcinoma of the lung, and we review the current literature on disseminated aspergillosis complicating neoplastic disease."}
{"id": "PMID:221156", "title": "Antiviral action of benzo[de]isoquinoline-1,3-diones: 5-nitro-2-(2-dimethylaminoethyl) and 5-nitro-2-[2-(1-pyrrolidine)-ethyl] derivatives.", "content": "Two benzo[de]isoquinoline-diones, namely 5-nitro-2-(2-dimethylaminoethyl)-benzo[de]isoquinoline-1,3-dione and 5-nitro-2-[2-(1-pyrrolidine)-ethyl]-benzo[de]isoquinoline-1,3-dione, caused inhibition of the viral replication, when assayed against herpes simplex and vaccinia viruses in chick embryo cell cultures. Influenza and Sindbis virus replication were unaffected by these chemicals. Virucidal effects were unobserved. The inhibitory activity is time-related. Ocular and dermal infections with vaccinia virus in rabbits were prevented or disease severity reduced whenever they were treated with either one of these two drugs.", "contents": "Antiviral action of benzo[de]isoquinoline-1,3-diones: 5-nitro-2-(2-dimethylaminoethyl) and 5-nitro-2-[2-(1-pyrrolidine)-ethyl] derivatives. Two benzo[de]isoquinoline-diones, namely 5-nitro-2-(2-dimethylaminoethyl)-benzo[de]isoquinoline-1,3-dione and 5-nitro-2-[2-(1-pyrrolidine)-ethyl]-benzo[de]isoquinoline-1,3-dione, caused inhibition of the viral replication, when assayed against herpes simplex and vaccinia viruses in chick embryo cell cultures. Influenza and Sindbis virus replication were unaffected by these chemicals. Virucidal effects were unobserved. The inhibitory activity is time-related. Ocular and dermal infections with vaccinia virus in rabbits were prevented or disease severity reduced whenever they were treated with either one of these two drugs."}
{"id": "PMID:221158", "title": "[A pneumatic colostomy closure].", "content": "An atraumatic, pneumatic occlusive colostomy appliance has been described which in animal experiments was well tolerated and was effective in preventing leakage. It is hoped that this may improve the unsatisfactory aspects of management in patients using conventional colostomy appliances.", "contents": "[A pneumatic colostomy closure]. An atraumatic, pneumatic occlusive colostomy appliance has been described which in animal experiments was well tolerated and was effective in preventing leakage. It is hoped that this may improve the unsatisfactory aspects of management in patients using conventional colostomy appliances."}
{"id": "PMID:221161", "title": "Malignant histiocytoma of the rectum: report of a case.", "content": "A case of malignant histiocytoma of the rectum has been described. We believe this is the first report of a case of this type. Other relevant reports are reviewed.", "contents": "Malignant histiocytoma of the rectum: report of a case. A case of malignant histiocytoma of the rectum has been described. We believe this is the first report of a case of this type. Other relevant reports are reviewed."}
{"id": "PMID:221162", "title": "[Haemofiltration in terminal renal failure (author's transl)].", "content": "The concentrations of low-molecular retention products rise during long-term haemodialysis, without any apparent side effects. The authors, having performed haemofiltration in 18 patients who had been on a chronic dialysis programme, conclude that haemofiltration is generally better tolerated than conventional haemodialysis. Haemofiltration benefitted the majority of dialysis-resistant hypertensives, and it also favourably influenced uraemic polyneuropathy. Indications for haemofiltration are thought to be dialysis-resistant hypertension, severe polyneuropathy, and dialysis intolerance.", "contents": "[Haemofiltration in terminal renal failure (author's transl)]. The concentrations of low-molecular retention products rise during long-term haemodialysis, without any apparent side effects. The authors, having performed haemofiltration in 18 patients who had been on a chronic dialysis programme, conclude that haemofiltration is generally better tolerated than conventional haemodialysis. Haemofiltration benefitted the majority of dialysis-resistant hypertensives, and it also favourably influenced uraemic polyneuropathy. Indications for haemofiltration are thought to be dialysis-resistant hypertension, severe polyneuropathy, and dialysis intolerance."}
{"id": "PMID:221166", "title": "Effects of adenosine 3',5'-monophosphate, dibutyryl adenosine 3',5'-monophosphate, aminophylline, and imidazole on renal cellular calcium metabolism.", "content": "The effects of cAMP, dibutyryl cAMP (DBcAMP), aminophylline, and imidazole on total cell calcium, calcium transport, and distribution were studied in cultured kidney cells by kinetic analysis of 45Ca uptake and desaturation curves. Low concentrations of the cyclic nucleotides (10(-7) and 10(-5) M) increase the total cell calcium, all intracellular exchangeable pools, and calcium transport between all cellular compartments. Aminophylline (1 mM) has effects qualitatively similar to cAMP and DBcAMP, while imidazole has opposite effects. At concentrations of 15 and 40 mM, imidazole depresses the total cell calcium and the cellular exchangeable calcium. Compared to the effects of parathyroid hormone (PTH), the changes obtained with 10(-7) and 10(-5) M cAMP are relatively modest, but higher concentrations (10(-3) M) of both cAMP and DBcAMP produce stimulations as marked as with 15 ng/ml PTH. The most dramatic changes are seen in the mitochondrial calcium pool and in the mitochondrial calcium exchange, which increase between 20- and 40-fold. These experiments show that cAMP mimics the effect of PTH on kidney cells and support the theory that cAMP is the mediator of PTH action on renal cell calcium transport.", "contents": "Effects of adenosine 3',5'-monophosphate, dibutyryl adenosine 3',5'-monophosphate, aminophylline, and imidazole on renal cellular calcium metabolism. The effects of cAMP, dibutyryl cAMP (DBcAMP), aminophylline, and imidazole on total cell calcium, calcium transport, and distribution were studied in cultured kidney cells by kinetic analysis of 45Ca uptake and desaturation curves. Low concentrations of the cyclic nucleotides (10(-7) and 10(-5) M) increase the total cell calcium, all intracellular exchangeable pools, and calcium transport between all cellular compartments. Aminophylline (1 mM) has effects qualitatively similar to cAMP and DBcAMP, while imidazole has opposite effects. At concentrations of 15 and 40 mM, imidazole depresses the total cell calcium and the cellular exchangeable calcium. Compared to the effects of parathyroid hormone (PTH), the changes obtained with 10(-7) and 10(-5) M cAMP are relatively modest, but higher concentrations (10(-3) M) of both cAMP and DBcAMP produce stimulations as marked as with 15 ng/ml PTH. The most dramatic changes are seen in the mitochondrial calcium pool and in the mitochondrial calcium exchange, which increase between 20- and 40-fold. These experiments show that cAMP mimics the effect of PTH on kidney cells and support the theory that cAMP is the mediator of PTH action on renal cell calcium transport."}
{"id": "PMID:221173", "title": "Adenosine 3',5'-monophosphate effects on cartilage ribonucleic acid synthesis.", "content": "We have previously shown that N6-monobutyryl-cAMP stimulates the incorporation of radiolabeled precursors into the macromolecules of embryonic chicken cartilage incubated in organ culture. The present study assessed the specific effects of N6-monobutyryl-cAMP on RNA synthesis in the cartilage organ culture system. The data show that treatment of cartilage with N6-monobutyryl-cAMP results in a coordinated stimulation of mRNA, rTNA, and tRNA synthesis. Incubation of cartilage with N6-monobutyryl-cAMP causes an increase of [5-3H]uridine incorporation into poly A-containing cartilage RNA and 28S, 18S, and 4S RNA as well. Increased incorporation of the radiolabeled nucleotide occurs without a measurable change in uridine triphosphate specific activity or in the rate of RNA degradation. Further, the isolated poly A-containing RNA directs protein synthesis in an in vitro cell-free system, and stimulation of cartilage mRNA by N6-monobutyryl-cAMP does not alter the size distribution of the mRNA species synthesized from that present in control tissue. These data indicate that cAMP enhances cartilage transcriptional activity. In addition, the increased synthesis of mRNA occurs antecedent to demonstrable effects on protein synthesis. Thus, the effects of cAMP on protein synthesis may be secondary to action at the nucleus.", "contents": "Adenosine 3',5'-monophosphate effects on cartilage ribonucleic acid synthesis. We have previously shown that N6-monobutyryl-cAMP stimulates the incorporation of radiolabeled precursors into the macromolecules of embryonic chicken cartilage incubated in organ culture. The present study assessed the specific effects of N6-monobutyryl-cAMP on RNA synthesis in the cartilage organ culture system. The data show that treatment of cartilage with N6-monobutyryl-cAMP results in a coordinated stimulation of mRNA, rTNA, and tRNA synthesis. Incubation of cartilage with N6-monobutyryl-cAMP causes an increase of [5-3H]uridine incorporation into poly A-containing cartilage RNA and 28S, 18S, and 4S RNA as well. Increased incorporation of the radiolabeled nucleotide occurs without a measurable change in uridine triphosphate specific activity or in the rate of RNA degradation. Further, the isolated poly A-containing RNA directs protein synthesis in an in vitro cell-free system, and stimulation of cartilage mRNA by N6-monobutyryl-cAMP does not alter the size distribution of the mRNA species synthesized from that present in control tissue. These data indicate that cAMP enhances cartilage transcriptional activity. In addition, the increased synthesis of mRNA occurs antecedent to demonstrable effects on protein synthesis. Thus, the effects of cAMP on protein synthesis may be secondary to action at the nucleus."}
{"id": "PMID:221174", "title": "Daily rhythms in adrenal responsiveness to adrenocorticotropin are determined primarily by the time of feeding in the rat.", "content": "These experiments were done to determine: 1) whether feeding-related shifts in daily corticosterone rhythms are dependent upon changes in ACTH rhythms, 2) whether restricted feeding of rats results in abnormally high ACTH and corticosterone levels (i.e. stress), and 3) whether changes in either insulin or glucose levels might be the concomitants of feeding that change adrenal responsiveness to ACTH. Young male rats (80--90 g) on a 12-h light, 12-h dark cycle were allowed access to one of three diets for 2 h/day beginning either at lights off or lights on. The diets contained 3%, 4.5%, or 11% fat. A group of rats had ad libitum access to the food containing 4.5% fat. On day 20 of this regimen, rats were killed at 2- to 4-h intervals during the next 24 h, and plasma ACTH, corticosterone, insulin, and glucose were measured. Adrenal weight and corticosterone content were also determined. In none of these experiments was an ACTH rhythm demonstrable by analysis of variance. Neither ACTH levels nor adrenal and plasma corticosterone levels were higher in animals fed 2 h/day than in rats eating ad libitum. Peak corticosterone levels occurred just before feeding, and the restricted feeding paradigm appeard to sharpen the daily rhythms. However, there was also an effect of the light-dark cycle on corticosterone measures. Dietary fat content was directly related to increases in body weight and mean insulin levels and infersely related to adrenal responsiveness to ACTH. The data show that: 1) the time of feeding determines the timing of the corticosterone rhythm in the absence of a rhythm in ACTH, 2) restricted feeding is not a stress, and 3) neither insulin nor glucose has a substantial influence on adrenal responsiveness to ACTH.", "contents": "Daily rhythms in adrenal responsiveness to adrenocorticotropin are determined primarily by the time of feeding in the rat. These experiments were done to determine: 1) whether feeding-related shifts in daily corticosterone rhythms are dependent upon changes in ACTH rhythms, 2) whether restricted feeding of rats results in abnormally high ACTH and corticosterone levels (i.e. stress), and 3) whether changes in either insulin or glucose levels might be the concomitants of feeding that change adrenal responsiveness to ACTH. Young male rats (80--90 g) on a 12-h light, 12-h dark cycle were allowed access to one of three diets for 2 h/day beginning either at lights off or lights on. The diets contained 3%, 4.5%, or 11% fat. A group of rats had ad libitum access to the food containing 4.5% fat. On day 20 of this regimen, rats were killed at 2- to 4-h intervals during the next 24 h, and plasma ACTH, corticosterone, insulin, and glucose were measured. Adrenal weight and corticosterone content were also determined. In none of these experiments was an ACTH rhythm demonstrable by analysis of variance. Neither ACTH levels nor adrenal and plasma corticosterone levels were higher in animals fed 2 h/day than in rats eating ad libitum. Peak corticosterone levels occurred just before feeding, and the restricted feeding paradigm appeard to sharpen the daily rhythms. However, there was also an effect of the light-dark cycle on corticosterone measures. Dietary fat content was directly related to increases in body weight and mean insulin levels and infersely related to adrenal responsiveness to ACTH. The data show that: 1) the time of feeding determines the timing of the corticosterone rhythm in the absence of a rhythm in ACTH, 2) restricted feeding is not a stress, and 3) neither insulin nor glucose has a substantial influence on adrenal responsiveness to ACTH."}
{"id": "PMID:221175", "title": "Subcellular localization of thyroxine and reverse triiodothyronine outer ring monodeiodinating activities.", "content": "In order to examine the subcellular localization of outer ring T4- and rT3-monodeiodinating activities, nuclear, mitochondrial, microsomal, cytosol, and plasma membrane fractions of rat liver homogenate were incubated with either T4 or rT3 in phosphate buffer (pH 7.35) in the presence of 2 mM dithiothreitol for 15 min at 37 C, and the amount of product (T3 in the case of T4 and 3,3'-diiodothyronine in the case of rT3) was measured by specific RIA. The various tissue fractions were also examined for the relative concentration of various marker enzymes. T4 and rT3 monodeiodinating activities correlated better with enzyme markers of plasma membranes than of any other subcellular fraction in most tissue fractions. A fraction could be isolated, however, in which the monodeiodinating activities correlated better with the enzyme markers of microsomes than of plasma membranes. The various data suggest that plasma membranes and microsomes are two main sites of T4- and rT3-monodeiodinating activities. The location of T4 to T3 converting activity in the plasma membranes may serve to modulate the delivery of the more potent thyroid hormone, i.e. T3, into the cells.", "contents": "Subcellular localization of thyroxine and reverse triiodothyronine outer ring monodeiodinating activities. In order to examine the subcellular localization of outer ring T4- and rT3-monodeiodinating activities, nuclear, mitochondrial, microsomal, cytosol, and plasma membrane fractions of rat liver homogenate were incubated with either T4 or rT3 in phosphate buffer (pH 7.35) in the presence of 2 mM dithiothreitol for 15 min at 37 C, and the amount of product (T3 in the case of T4 and 3,3'-diiodothyronine in the case of rT3) was measured by specific RIA. The various tissue fractions were also examined for the relative concentration of various marker enzymes. T4 and rT3 monodeiodinating activities correlated better with enzyme markers of plasma membranes than of any other subcellular fraction in most tissue fractions. A fraction could be isolated, however, in which the monodeiodinating activities correlated better with the enzyme markers of microsomes than of plasma membranes. The various data suggest that plasma membranes and microsomes are two main sites of T4- and rT3-monodeiodinating activities. The location of T4 to T3 converting activity in the plasma membranes may serve to modulate the delivery of the more potent thyroid hormone, i.e. T3, into the cells."}
{"id": "PMID:221176", "title": "Effects of hypophysectomy, thyroidectomy, and thyroxine on specific prolactin receptor sites in kidneys and adrenals of male rats.", "content": "The effect of T4 on specific PRL binding in the kidneys and adrenals was measured in intact, hypophysectomized, and thyroidectomized male rats. PRL binding in the kidneys was reduced from 12.1 +/- 1.1% in the intact group to 4.5 +/- 0.5% after hypophysectomy; 4-day replacement with T4 returned PRL binding to intact values. T4 administered to intact rats significantly increased PRL binding above intact values. Thyroidectomy reduced PRL binding in the kidneys from 14.9 +/- 1.2% to 7.0 +/- 0.6%, and T4 treatment restored PRL binding to intact values. PRL binding was measured at 2, 3, 5, 7, and 10 days after thyroidectomy in kidneys and found to decrease progressively from 8.2+/-0.5% in the intact rats to 2.3+/-0.3% on day 10. A single injection of T4 doubled PRL recetor binding in kidneys of thyroidectomized rats at 12 h and returned binding to intact levels at 24 h. In contrast to the effects of T4 on kidney PRL binding, adrenal PRL binding was only slightly altered by thyroidectomy and T4. These results suggest that T4 has a specific role in regulating PRL receptors in the kidneys but not in the adrenals. Since PRL receptors in the adrenals were only slightly altered by thyroid status, it is believed that the changes in kidney receptors represent a specific rather than a general metabolic effect of T4.", "contents": "Effects of hypophysectomy, thyroidectomy, and thyroxine on specific prolactin receptor sites in kidneys and adrenals of male rats. The effect of T4 on specific PRL binding in the kidneys and adrenals was measured in intact, hypophysectomized, and thyroidectomized male rats. PRL binding in the kidneys was reduced from 12.1 +/- 1.1% in the intact group to 4.5 +/- 0.5% after hypophysectomy; 4-day replacement with T4 returned PRL binding to intact values. T4 administered to intact rats significantly increased PRL binding above intact values. Thyroidectomy reduced PRL binding in the kidneys from 14.9 +/- 1.2% to 7.0 +/- 0.6%, and T4 treatment restored PRL binding to intact values. PRL binding was measured at 2, 3, 5, 7, and 10 days after thyroidectomy in kidneys and found to decrease progressively from 8.2+/-0.5% in the intact rats to 2.3+/-0.3% on day 10. A single injection of T4 doubled PRL recetor binding in kidneys of thyroidectomized rats at 12 h and returned binding to intact levels at 24 h. In contrast to the effects of T4 on kidney PRL binding, adrenal PRL binding was only slightly altered by thyroidectomy and T4. These results suggest that T4 has a specific role in regulating PRL receptors in the kidneys but not in the adrenals. Since PRL receptors in the adrenals were only slightly altered by thyroid status, it is believed that the changes in kidney receptors represent a specific rather than a general metabolic effect of T4."}
{"id": "PMID:221177", "title": "Dissociation of glucocorticoid inhibition of glucose transport and metabolism by increase in adipocyte age and/or size.", "content": "Exposure of adipocytes from young rats (2--3 months old) to dexamethasone in vitro results in 40--50% inhibition of glucose transport and metabolism. Comparable experiments with older rats reveal that the hormonal effect on glucose metabolism is progressively reduced to about 20% in 12- to 13-month-old animals and about 5% in 24- to 26-month-old animals. However, no effect of dexamethasone on the glucose transport system can be detected in either of the older age groups when three different sugars are used to measure transport activity. The ability of dexamethasone to inhibit glucose phosphorylation seems to be closely related to inhibition of overall glucose oxidation in both young and old adipocytes. That the membrane may be generally more resistant to control of glucose transport is suggested by failure or reduced ability of insulin, vitamin K5, and hydrogen peroxide to stimulate this function in older cells.", "contents": "Dissociation of glucocorticoid inhibition of glucose transport and metabolism by increase in adipocyte age and/or size. Exposure of adipocytes from young rats (2--3 months old) to dexamethasone in vitro results in 40--50% inhibition of glucose transport and metabolism. Comparable experiments with older rats reveal that the hormonal effect on glucose metabolism is progressively reduced to about 20% in 12- to 13-month-old animals and about 5% in 24- to 26-month-old animals. However, no effect of dexamethasone on the glucose transport system can be detected in either of the older age groups when three different sugars are used to measure transport activity. The ability of dexamethasone to inhibit glucose phosphorylation seems to be closely related to inhibition of overall glucose oxidation in both young and old adipocytes. That the membrane may be generally more resistant to control of glucose transport is suggested by failure or reduced ability of insulin, vitamin K5, and hydrogen peroxide to stimulate this function in older cells."}
{"id": "PMID:221178", "title": "Gonadotropin-releasing hormone action in cultured pituicytes: independence of luteinizing hormone release and adenosine 3',5'-monophosphate production.", "content": "The secretory response of pituitary gonadotropes to stimulation by gonadotropin-releasing hormone (GnRH) has been extensively studied, but the mechanism by which GnRH evokes gonadotropin synthesis and release has not been clarified. In particular, there has been conflicting evidence about the role of cAMP in GnRH-induced release of LH. To examine this question in more detail, the actions of GnRH on LH release and cAMP production were analyzed in primary cultures of collagenase-dispersed rat pituitary cells. In this system, addition of 10(-10)--10(-6) M GnRh to cultured pituicytes caused rapid release of LH into the incubation medium. In contrast, GnRH caused no significant change in intracellular or extracellular cAMP or in occupancy by cAMP of the regulatory subunit of protein kinse. Neither dibutyryl cAMP nor methyl isobutylxanthine (MIC) stimulated LH production to the same level as GnRH, and neither agent potentiated the effect of the releasing hormone. Cholera toxin and prostaglandin E1 (PGE1), both of which stimulated cAMP production in cultured pituicytes, did not raise LH levels as markedly as GnRH. These results demonstrate the independence of LH release from cAMP accumulation in cultured pituicytes, suggesting that cAMP is not required for stimulation of LH release from these cells and that GnRH acts on LH secretion by a different mechanism.", "contents": "Gonadotropin-releasing hormone action in cultured pituicytes: independence of luteinizing hormone release and adenosine 3',5'-monophosphate production. The secretory response of pituitary gonadotropes to stimulation by gonadotropin-releasing hormone (GnRH) has been extensively studied, but the mechanism by which GnRH evokes gonadotropin synthesis and release has not been clarified. In particular, there has been conflicting evidence about the role of cAMP in GnRH-induced release of LH. To examine this question in more detail, the actions of GnRH on LH release and cAMP production were analyzed in primary cultures of collagenase-dispersed rat pituitary cells. In this system, addition of 10(-10)--10(-6) M GnRh to cultured pituicytes caused rapid release of LH into the incubation medium. In contrast, GnRH caused no significant change in intracellular or extracellular cAMP or in occupancy by cAMP of the regulatory subunit of protein kinse. Neither dibutyryl cAMP nor methyl isobutylxanthine (MIC) stimulated LH production to the same level as GnRH, and neither agent potentiated the effect of the releasing hormone. Cholera toxin and prostaglandin E1 (PGE1), both of which stimulated cAMP production in cultured pituicytes, did not raise LH levels as markedly as GnRH. These results demonstrate the independence of LH release from cAMP accumulation in cultured pituicytes, suggesting that cAMP is not required for stimulation of LH release from these cells and that GnRH acts on LH secretion by a different mechanism."}
{"id": "PMID:221180", "title": "Inhibitory effects of corticosterone on cell proliferation and steroidogenesis in the mouse adrenal tumor cell line Y-1.", "content": "Monolayer cultures of mouse adrenal tumor cell line Y-1 have been used to investigate the effects of glucocorticoid on cell replication, [3H]thymidine incorporation into the trichloroacetic acid-precipitated cell fraction, steroidogenesis, and the ACTH receptors of adrenocortical cells. Corticosterone at a concentration of 5.0--50 micrograms/ml inhibited cell replication and [3H]thymidine incorporation into trichloroacetic acid-precipitated cell fraction in a dose-related manner. Corticosterone at a concentration of 0.5--50 micrograms/ml inhibited ACTH-induced steroidogenesis in a dose-related manner. Steroids which do not possess glucocorticoid action did not show such inhibitory effects on cell replication and steroidogenesis of Y-1 cells. The characteristics of the ACTH receptors of these cells remained unaffected by corticosterone. Our findings suggest that synthesized or secreted glucocorticoid may play an important role in the direct regulation of proliferation and function of adrenocortical cells under physiological conditions.", "contents": "Inhibitory effects of corticosterone on cell proliferation and steroidogenesis in the mouse adrenal tumor cell line Y-1. Monolayer cultures of mouse adrenal tumor cell line Y-1 have been used to investigate the effects of glucocorticoid on cell replication, [3H]thymidine incorporation into the trichloroacetic acid-precipitated cell fraction, steroidogenesis, and the ACTH receptors of adrenocortical cells. Corticosterone at a concentration of 5.0--50 micrograms/ml inhibited cell replication and [3H]thymidine incorporation into trichloroacetic acid-precipitated cell fraction in a dose-related manner. Corticosterone at a concentration of 0.5--50 micrograms/ml inhibited ACTH-induced steroidogenesis in a dose-related manner. Steroids which do not possess glucocorticoid action did not show such inhibitory effects on cell replication and steroidogenesis of Y-1 cells. The characteristics of the ACTH receptors of these cells remained unaffected by corticosterone. Our findings suggest that synthesized or secreted glucocorticoid may play an important role in the direct regulation of proliferation and function of adrenocortical cells under physiological conditions."}
{"id": "PMID:221182", "title": "Metabolism of parathyroid hormone by fetal rat calvaria.", "content": "These studies examine the metabolism of highly purified bovine parathyroid hormone [bPTH-(1--84)] by fetal rat calvaria. Enzymatically dispersed bone cells and intact (minced) calvaria were incubated with bPTH-(1--84) and the incubation medium was analyzed for degradation of PTH by polyacrylamide gel electrophoresis. Eluates of gel slices were assayed for immunoreactive PTH (iPTH) in carboxy- and amino-terminal RIAs. Both bone preparations metabolized bPTH-(1--84). The intact hormone progessively decreased with time and carboxy-terminal iPTH fragments were evident by 5 min of incubation. In the isolated cell preparations, intact hormone was completely degraded at submaximal doses of PTH (5 X 10(-9) M), as assessed by cAMP production. Degradation was incomplete in intact calvarial preparations at all doses studied. Intact calvaria were less sensitive to PTH with regard to cAMP production. No amino-terminal fragments were detected in the medium with either cell preparation. Oxidized (biologically inactive) bPTH-(1--84) was not metabolized in these systems. These findings contrast with studies in liver and kidney preparations, where oxidized bPTH has been shown to be degraded. These findings contrast with studies in liver and kidney preparations, where oxidized bPTH has been shown to be degraded. These data suggest that biological activity may be necessary for the metabolism of intact bPTH-(1--84) by bone cells and that skeletal tissue may contribute to the immunoheterogeneity of circulating PTH in the rat.", "contents": "Metabolism of parathyroid hormone by fetal rat calvaria. These studies examine the metabolism of highly purified bovine parathyroid hormone [bPTH-(1--84)] by fetal rat calvaria. Enzymatically dispersed bone cells and intact (minced) calvaria were incubated with bPTH-(1--84) and the incubation medium was analyzed for degradation of PTH by polyacrylamide gel electrophoresis. Eluates of gel slices were assayed for immunoreactive PTH (iPTH) in carboxy- and amino-terminal RIAs. Both bone preparations metabolized bPTH-(1--84). The intact hormone progessively decreased with time and carboxy-terminal iPTH fragments were evident by 5 min of incubation. In the isolated cell preparations, intact hormone was completely degraded at submaximal doses of PTH (5 X 10(-9) M), as assessed by cAMP production. Degradation was incomplete in intact calvarial preparations at all doses studied. Intact calvaria were less sensitive to PTH with regard to cAMP production. No amino-terminal fragments were detected in the medium with either cell preparation. Oxidized (biologically inactive) bPTH-(1--84) was not metabolized in these systems. These findings contrast with studies in liver and kidney preparations, where oxidized bPTH has been shown to be degraded. These findings contrast with studies in liver and kidney preparations, where oxidized bPTH has been shown to be degraded. These data suggest that biological activity may be necessary for the metabolism of intact bPTH-(1--84) by bone cells and that skeletal tissue may contribute to the immunoheterogeneity of circulating PTH in the rat."}
{"id": "PMID:221183", "title": "Intestinal calcium-binding protein and calcium absorption in cortisol-treated chicks: effects of vitamin D3 and 1,25-dihydroxyvitamin D3.", "content": "Vitamin D3 in rachitic chicks stimulates calcium absorption and induces the synthesis of two pools of intestinal calcium-binding protein (CaBP), one soluble and the other membrane bound. Cortisol acetate caused a decrease in calcium absorption which was accompanied by a decrease in soluble CaBP. Cortisol was similarly effective in 1,25-dihydroxyvitamin D3-dosed chicks, suggesting that the glucocorticoid effect was not entirely due to the defective synthesis of this metabolite. Ca absorption was directly correlated with soluble CaBP and alkaline phosphatase and inversely related to the ratio of bound to soluble CaBP. It was further observed that the slope of the Ca absorption vs. soluble CaBP regression line was greater in chicks given 1,25-dihyroxyvitamin D3 compared to those given vitamin D3, and this is interpreted to mean that another factor or condition, in addition to assayed concentrations of soluble CaBP, determines the degree of calcium absorption.", "contents": "Intestinal calcium-binding protein and calcium absorption in cortisol-treated chicks: effects of vitamin D3 and 1,25-dihydroxyvitamin D3. Vitamin D3 in rachitic chicks stimulates calcium absorption and induces the synthesis of two pools of intestinal calcium-binding protein (CaBP), one soluble and the other membrane bound. Cortisol acetate caused a decrease in calcium absorption which was accompanied by a decrease in soluble CaBP. Cortisol was similarly effective in 1,25-dihydroxyvitamin D3-dosed chicks, suggesting that the glucocorticoid effect was not entirely due to the defective synthesis of this metabolite. Ca absorption was directly correlated with soluble CaBP and alkaline phosphatase and inversely related to the ratio of bound to soluble CaBP. It was further observed that the slope of the Ca absorption vs. soluble CaBP regression line was greater in chicks given 1,25-dihyroxyvitamin D3 compared to those given vitamin D3, and this is interpreted to mean that another factor or condition, in addition to assayed concentrations of soluble CaBP, determines the degree of calcium absorption."}
{"id": "PMID:221185", "title": "Parathyroid hormone stimulation of collagenase secretion by isolated bone cells.", "content": "Cells isolated from fetal rat calvaria were cultured in a [14C]glycine-labeled collagen gel. This method of culture places the cells in an environment similar to that in the intact tissue and provides a means for assaying the release of collagenase from the cells. Degradation of the collagen matrix begins within the first 3 h of cell culture, the earliest time point at which samples were taken, and continues for at least 12 h. When cells were prepared from calvaria incubated for 30 min with parathyroid hormone (PTH), there was a marked decrease in the collagenase content of the freshly isolated cells, indicating that secretion of collagenase had been enhanced by PTH. Upon subsequent culture of control and PTH-pretreated cells, there was an increase in lysis of collagen gels surrounding the hormone-treated cells within 8 h. The increased collagenolysis was prevented by exposure of the cells to puromycin before and during culture, suggesting that collagenase synthesis also was stimulated by PTH.", "contents": "Parathyroid hormone stimulation of collagenase secretion by isolated bone cells. Cells isolated from fetal rat calvaria were cultured in a [14C]glycine-labeled collagen gel. This method of culture places the cells in an environment similar to that in the intact tissue and provides a means for assaying the release of collagenase from the cells. Degradation of the collagen matrix begins within the first 3 h of cell culture, the earliest time point at which samples were taken, and continues for at least 12 h. When cells were prepared from calvaria incubated for 30 min with parathyroid hormone (PTH), there was a marked decrease in the collagenase content of the freshly isolated cells, indicating that secretion of collagenase had been enhanced by PTH. Upon subsequent culture of control and PTH-pretreated cells, there was an increase in lysis of collagen gels surrounding the hormone-treated cells within 8 h. The increased collagenolysis was prevented by exposure of the cells to puromycin before and during culture, suggesting that collagenase synthesis also was stimulated by PTH."}
{"id": "PMID:221188", "title": "Oxidative metabolites of [2-14C]propylthiouracil in rat thyroid.", "content": "The identities and relative amounts of the major metabolites in rat thyroids 6 h after the administration of [14C]propylthiouracil ([14C]PTU) have been investigated. Rat thyroid extracts were chromatographed on columns of Bio-Gel P-2 and DEAE-Sephadex and in various thin layer chromatography systems. The extracts contained protein-bound PTU metabolites; an unknown peak 3; peak 1, which was chromatographically similar to PTU--SO2H; peak 2, which was similar to PTU--SO3H; PTU; and small amounts of 6-n-propyluracil (PU). The major metabolites were isolated and purified by column chromatograpy. On the basis of chromatographic properties identical to cochromatographed standards in seven different systems and the products formed after treatment with various reagents, peak 1 was identified as PTU-SO2H and peak 2 as PTU--SO3H. Peak 3 was seen only on Bio-Gel P-2 columns, was very unstable, and was not similar to any known PTU standard. The properties of this compound suggest that it may be a thiolsulfonic ester (formula:see text), but the data are insufficient for positive identification. Approximately 85% of the radioactivity in the protein peak was bound to thyroglobulin. HCl converted 86.5% of the protein-bound radioactivity to PU, and H2S converted 91% to PTU, indicating that an oxidized S was involved in the linkage to protein. Dithiothreitol released 23.6% of the protein-bound radioactivity as PTU, and mercaptoethanol released 32.5%, indicating that 25-35% of the PTU is bound in disulfide linkage. Approximately 50% of the radioactivity released by mercaptoethanol was S-ethanol PTU, which suggests a PTU-protein bond similar to a thiolsulfonic ester. Quantitation of the metabolites revealed that protein-bound metabolites accounted for 21-29% of the total radioactivity, unknown peak 3 accounted for 7.1%, PTU--SO2H for 48-50%, PTU--SO3H for 8-10%, and PTU for 10.7-16.5%. Only traces of PU were observed. The data demonstrate that PTU--SO2H is the major PTU metabolite in rat thyroid and must be the compound X observed by other investigators and that all metabolites identified are oxidative products of PTU. These findings support the earlier conclusion of Taurog and Riesco that protein binding of PTU occurs as a consequence of oxidation.", "contents": "Oxidative metabolites of [2-14C]propylthiouracil in rat thyroid. The identities and relative amounts of the major metabolites in rat thyroids 6 h after the administration of [14C]propylthiouracil ([14C]PTU) have been investigated. Rat thyroid extracts were chromatographed on columns of Bio-Gel P-2 and DEAE-Sephadex and in various thin layer chromatography systems. The extracts contained protein-bound PTU metabolites; an unknown peak 3; peak 1, which was chromatographically similar to PTU--SO2H; peak 2, which was similar to PTU--SO3H; PTU; and small amounts of 6-n-propyluracil (PU). The major metabolites were isolated and purified by column chromatograpy. On the basis of chromatographic properties identical to cochromatographed standards in seven different systems and the products formed after treatment with various reagents, peak 1 was identified as PTU-SO2H and peak 2 as PTU--SO3H. Peak 3 was seen only on Bio-Gel P-2 columns, was very unstable, and was not similar to any known PTU standard. The properties of this compound suggest that it may be a thiolsulfonic ester (formula:see text), but the data are insufficient for positive identification. Approximately 85% of the radioactivity in the protein peak was bound to thyroglobulin. HCl converted 86.5% of the protein-bound radioactivity to PU, and H2S converted 91% to PTU, indicating that an oxidized S was involved in the linkage to protein. Dithiothreitol released 23.6% of the protein-bound radioactivity as PTU, and mercaptoethanol released 32.5%, indicating that 25-35% of the PTU is bound in disulfide linkage. Approximately 50% of the radioactivity released by mercaptoethanol was S-ethanol PTU, which suggests a PTU-protein bond similar to a thiolsulfonic ester. Quantitation of the metabolites revealed that protein-bound metabolites accounted for 21-29% of the total radioactivity, unknown peak 3 accounted for 7.1%, PTU--SO2H for 48-50%, PTU--SO3H for 8-10%, and PTU for 10.7-16.5%. Only traces of PU were observed. The data demonstrate that PTU--SO2H is the major PTU metabolite in rat thyroid and must be the compound X observed by other investigators and that all metabolites identified are oxidative products of PTU. These findings support the earlier conclusion of Taurog and Riesco that protein binding of PTU occurs as a consequence of oxidation."}
{"id": "PMID:221189", "title": "Effects of glucocorticoids on microsomal membrane synthesis in hepatocytes from adrenalectomized rats.", "content": "Biochemical and morphological studies were performed on livers from normal, adrenalectomized (ADX), and ADX and dexamethasone (DEX)-treated rats to investigate the effects of glucocorticoids on microsomal membrane synthesis. Overnight fasted normal, ADX and ADX rats treated 2 or 4 h with DEX received [3H]leucine and [14C]glycerol. Livers were removed, and tissue specimens were prepared for electron microscopy and tissue fractionation. Liver microsomal subfractions were prepared and subsequently washed to produce rough and smooth microsomal membranes. Radioactivity and membrane composition were determined, and glucose-6-phosphatase activity was measured in washed microsomal membranes. Adrenalectomy caused decreased microsomal membrane synthesis. Two and 4 h of DEX administration restored microsomal membrane synthesis to normal levels. ADX also caused an alteration in composition of the microsomal membranes (reflected in decreased phospholipid-protein ratios), which was restored to normal levels by 4 h after DEX administration. The earliest effects of the hormone on membrane synthesis were observed in smooth microsomes as part of a smooth endoplasmic reticulum (SER) proliferation. These findings were supported by observations made with the electron microscope. The proliferating SER was enriched in at least one component: glucose-6-phosphatase. Although the specific relationship of SER to glucocorticoid action remains unclear, the interpretation is offered that SER proliferation and alteration in glucose-6-phosphatase distribution are component parts of the total response of the hepatocyte to glucocorticoids.", "contents": "Effects of glucocorticoids on microsomal membrane synthesis in hepatocytes from adrenalectomized rats. Biochemical and morphological studies were performed on livers from normal, adrenalectomized (ADX), and ADX and dexamethasone (DEX)-treated rats to investigate the effects of glucocorticoids on microsomal membrane synthesis. Overnight fasted normal, ADX and ADX rats treated 2 or 4 h with DEX received [3H]leucine and [14C]glycerol. Livers were removed, and tissue specimens were prepared for electron microscopy and tissue fractionation. Liver microsomal subfractions were prepared and subsequently washed to produce rough and smooth microsomal membranes. Radioactivity and membrane composition were determined, and glucose-6-phosphatase activity was measured in washed microsomal membranes. Adrenalectomy caused decreased microsomal membrane synthesis. Two and 4 h of DEX administration restored microsomal membrane synthesis to normal levels. ADX also caused an alteration in composition of the microsomal membranes (reflected in decreased phospholipid-protein ratios), which was restored to normal levels by 4 h after DEX administration. The earliest effects of the hormone on membrane synthesis were observed in smooth microsomes as part of a smooth endoplasmic reticulum (SER) proliferation. These findings were supported by observations made with the electron microscope. The proliferating SER was enriched in at least one component: glucose-6-phosphatase. Although the specific relationship of SER to glucocorticoid action remains unclear, the interpretation is offered that SER proliferation and alteration in glucose-6-phosphatase distribution are component parts of the total response of the hepatocyte to glucocorticoids."}
{"id": "PMID:221190", "title": "Adenosine 3',5'-monophosphate-dependent protein kinase activity in soluble thyrotropin receptor complex.", "content": "cAMP-dependent protein kinase activity was present in a soluble TSH receptor fraction. The Km of this enzyme was 2.2 X 10(-6) M for casein substrate in the absence or presence of 10(-5) M cAMP. A [3H]cAMP-binding protein was also found in this fraction. The Ka for [3H]cAMP-binding was 0.11 X 10(6) M-1, with a total binding capacity of 3 nmol/mg protein. After fractionation using a continuous sucrose density gradient, one of the several [125I]iodobovine TSH-binding peaks corresponded to a [3H]cAMP-binding peak. After fractionation on a sucrose density gradient containing 0.4 M NaCl at pH 6.5, a major peak of protein kinase activity was shown. This protein kinase activity was stimulated by adding 10(-5) M cAMP. A peak of [3H]cAMP-binding activity corresponded to the same peak. Protein kinase activity in the receptor fraction was stimulated by adding 6 mg/ml bovine TSH. The soluble TSH receptor fraction also has an adenylate cyclase activity stimulated by TSH. These results suggest that some TSH receptors released from thyroid plasma membranes have associated adenylate cyclase activity and cAMP-dependent protein kinase activity. The receptor, cyclase, and kinase activities may exist in a functional primary receptor unit which is spontaneously released from plasma membranes.", "contents": "Adenosine 3',5'-monophosphate-dependent protein kinase activity in soluble thyrotropin receptor complex. cAMP-dependent protein kinase activity was present in a soluble TSH receptor fraction. The Km of this enzyme was 2.2 X 10(-6) M for casein substrate in the absence or presence of 10(-5) M cAMP. A [3H]cAMP-binding protein was also found in this fraction. The Ka for [3H]cAMP-binding was 0.11 X 10(6) M-1, with a total binding capacity of 3 nmol/mg protein. After fractionation using a continuous sucrose density gradient, one of the several [125I]iodobovine TSH-binding peaks corresponded to a [3H]cAMP-binding peak. After fractionation on a sucrose density gradient containing 0.4 M NaCl at pH 6.5, a major peak of protein kinase activity was shown. This protein kinase activity was stimulated by adding 10(-5) M cAMP. A peak of [3H]cAMP-binding activity corresponded to the same peak. Protein kinase activity in the receptor fraction was stimulated by adding 6 mg/ml bovine TSH. The soluble TSH receptor fraction also has an adenylate cyclase activity stimulated by TSH. These results suggest that some TSH receptors released from thyroid plasma membranes have associated adenylate cyclase activity and cAMP-dependent protein kinase activity. The receptor, cyclase, and kinase activities may exist in a functional primary receptor unit which is spontaneously released from plasma membranes."}
{"id": "PMID:221192", "title": "Resensitization of the desensitized follicular adenylyl cyclase system to luteinizing hormone.", "content": "LH-induced desensitization of the adenylyl cyclase system in a cell-free membrane preparation from preovulatory porcine follicles exhibits a critical dependence upon Mg and ATP (1). The membrane-rich preparation was found to contain endogenous cAMP-dependent and cAMP-independent protein kinases as well as phosphorprotein phosphatases. Endogenous phosphatase activity was enchanced by by Mn2+ and dithiothreitol. The addition of either Mn2+ or dithiothreitol to the porcine follicular membrane preparation incubated under desensitizing conditions promoted a specific concentration-dependent reversal of the LH-induced desensitization of the adenylyl cyclase system. The addition of exogenous phosphoprotein phosphatase, partially purified from procine follicular cytosol, also reversed LH-induced desensitization in a concentration-dependent manner. Boiling of the phophatase preparation prevented reversal of desensitization. The addition of either exogenous beef heart cAMP-dependent protein kinase or heat-stable protein kinase inhibitor did not modify LH-induced desensitization of the follicular adenylyl cyclase system. These results provide indirect evidence that while LH-induced desensitization is not mediated by a cAMP-dependent protein kinase, reversal of desensitization can be promoted by activation of endogenous phosphatase and the addition of a homologous phosphatase preparation.", "contents": "Resensitization of the desensitized follicular adenylyl cyclase system to luteinizing hormone. LH-induced desensitization of the adenylyl cyclase system in a cell-free membrane preparation from preovulatory porcine follicles exhibits a critical dependence upon Mg and ATP (1). The membrane-rich preparation was found to contain endogenous cAMP-dependent and cAMP-independent protein kinases as well as phosphorprotein phosphatases. Endogenous phosphatase activity was enchanced by by Mn2+ and dithiothreitol. The addition of either Mn2+ or dithiothreitol to the porcine follicular membrane preparation incubated under desensitizing conditions promoted a specific concentration-dependent reversal of the LH-induced desensitization of the adenylyl cyclase system. The addition of exogenous phosphoprotein phosphatase, partially purified from procine follicular cytosol, also reversed LH-induced desensitization in a concentration-dependent manner. Boiling of the phophatase preparation prevented reversal of desensitization. The addition of either exogenous beef heart cAMP-dependent protein kinase or heat-stable protein kinase inhibitor did not modify LH-induced desensitization of the follicular adenylyl cyclase system. These results provide indirect evidence that while LH-induced desensitization is not mediated by a cAMP-dependent protein kinase, reversal of desensitization can be promoted by activation of endogenous phosphatase and the addition of a homologous phosphatase preparation."}
{"id": "PMID:221196", "title": "Production of long term steroid-producing granulosa cell cultures by cell hybridization.", "content": "Primary cultures of rat ovarian granulosa cells have been used extensively to study hormonal regulation of cellular function. To date, no long term cultures of ovarian cells which retain their differentiated functions have been developed. Hypoxanthine guanine phosphoribosyl transferase-deficient simian virus 40-transformed rat ovarian granulosa cells were fused with freshly prepared rat granulosa cells using inactivated Sendai virus. Putative hybrid cell strains obtained after selection in medium containing hypoxanthine, aminopterin, and thymidine were analyzed for progesterone synthesis. Neither the original simian virus 40-transformed granulosa cell nor its hypoxanthine guanine phosphoribosyl transferase-deficient derivative produced progesterone, but three of the hybrid strains produced progesterone at basal levels and in response to dibutyryl cAMP. One of these strains produced progesterone in a dose-responsive fashion when exposed to prostaglandin E2, cholera toxin, dibutyryl cAMP, and 2-chloroadenosine. Cell strains obtained by hybridization were remarkably similar to primary cultures of granulosa cells with respect to both the magnitude and temporal aspects of progesterone production in response to dibutyryl cAMP.", "contents": "Production of long term steroid-producing granulosa cell cultures by cell hybridization. Primary cultures of rat ovarian granulosa cells have been used extensively to study hormonal regulation of cellular function. To date, no long term cultures of ovarian cells which retain their differentiated functions have been developed. Hypoxanthine guanine phosphoribosyl transferase-deficient simian virus 40-transformed rat ovarian granulosa cells were fused with freshly prepared rat granulosa cells using inactivated Sendai virus. Putative hybrid cell strains obtained after selection in medium containing hypoxanthine, aminopterin, and thymidine were analyzed for progesterone synthesis. Neither the original simian virus 40-transformed granulosa cell nor its hypoxanthine guanine phosphoribosyl transferase-deficient derivative produced progesterone, but three of the hybrid strains produced progesterone at basal levels and in response to dibutyryl cAMP. One of these strains produced progesterone in a dose-responsive fashion when exposed to prostaglandin E2, cholera toxin, dibutyryl cAMP, and 2-chloroadenosine. Cell strains obtained by hybridization were remarkably similar to primary cultures of granulosa cells with respect to both the magnitude and temporal aspects of progesterone production in response to dibutyryl cAMP."}
{"id": "PMID:221199", "title": "Estrogens increase the number of thyrotropin-releasing hormone receptors on mammotropic cells in culture.", "content": "The number of plasma membrane receptors for TRH on tumor-derived mammotropic cells in culture, GH3 and GC cells, but not their affinity for TRH, was increased by estrogens. For GH3 cells, exposure to 10 nM 17 beta-estradiol for 48 h increased the receptor level from 54,000 to 90,000 sites/cell, while for GC cells, the number of receptors increased from 29,000 to 46,000 after 28 h. PRL accumulation in the medium was also increased by 17 beta-estradiol. 17 beta-Estradiol and diethylstilbestrol were equally potent in increasing the TRH receptor level, while estrone was only 1/10th as potent. Diethylstilbestrol bound to the cytoplasmic estrogen receptor with an apparent affinity approximately 2.5 times higher than 17 beta-estradiol in GH3 and GC cells, while the affinity for estrone was only 1/12th to 1/20th that of 17 beta-estradiol. Tamoxifen, an antiestrogenic compound, inhibited the increase in TRH receptor number induced by 0.3 nM 17 beta-estradiol and was capable of binding to the estrogen receptor. Modulation of the TRH receptor level on mammotropic cells by estrogens, which is likely mediated through cytoplasmic estrogen receptors, may be an important mechanism for regulation of TRH action.", "contents": "Estrogens increase the number of thyrotropin-releasing hormone receptors on mammotropic cells in culture. The number of plasma membrane receptors for TRH on tumor-derived mammotropic cells in culture, GH3 and GC cells, but not their affinity for TRH, was increased by estrogens. For GH3 cells, exposure to 10 nM 17 beta-estradiol for 48 h increased the receptor level from 54,000 to 90,000 sites/cell, while for GC cells, the number of receptors increased from 29,000 to 46,000 after 28 h. PRL accumulation in the medium was also increased by 17 beta-estradiol. 17 beta-Estradiol and diethylstilbestrol were equally potent in increasing the TRH receptor level, while estrone was only 1/10th as potent. Diethylstilbestrol bound to the cytoplasmic estrogen receptor with an apparent affinity approximately 2.5 times higher than 17 beta-estradiol in GH3 and GC cells, while the affinity for estrone was only 1/12th to 1/20th that of 17 beta-estradiol. Tamoxifen, an antiestrogenic compound, inhibited the increase in TRH receptor number induced by 0.3 nM 17 beta-estradiol and was capable of binding to the estrogen receptor. Modulation of the TRH receptor level on mammotropic cells by estrogens, which is likely mediated through cytoplasmic estrogen receptors, may be an important mechanism for regulation of TRH action."}
{"id": "PMID:221200", "title": "Cyclic nucleotide-dependent protein kinase modulators in thyroid tissue.", "content": "A heat-stable protein which inhibits cAMP dependent protein kinase was prepared from the bovine thyroid 100,000 X g supernatant. This protein inhibited the cAMP-dependent protein kinase both from bovine thyroid cytosol and bovine thyroid plasma membranes. The inhibitory effect was noncompetitive with histone as substrate of the cytosolic enzyme. The stimulatory modulator for cGMP-dependent protein kinase was separated from the 100,000 X g supernatant by Sephadex G-100 gel filtration. The stimulatory modulator had no stimulating effect on cAMP-dependent phosphorylation, and the inhibitory modulator of cAMP-dependent enzyme had no effect on cGMP-requiring phosphorylations. The inhibitory modulator may regulate cAMP-dependent protein kinase activity in cytosol and plasma membrane, and the stimulatory modulator for cGMP-dependent protein kinase may have a role in thyroid function independent of the cAMP-requiring system.", "contents": "Cyclic nucleotide-dependent protein kinase modulators in thyroid tissue. A heat-stable protein which inhibits cAMP dependent protein kinase was prepared from the bovine thyroid 100,000 X g supernatant. This protein inhibited the cAMP-dependent protein kinase both from bovine thyroid cytosol and bovine thyroid plasma membranes. The inhibitory effect was noncompetitive with histone as substrate of the cytosolic enzyme. The stimulatory modulator for cGMP-dependent protein kinase was separated from the 100,000 X g supernatant by Sephadex G-100 gel filtration. The stimulatory modulator had no stimulating effect on cAMP-dependent phosphorylation, and the inhibitory modulator of cAMP-dependent enzyme had no effect on cGMP-requiring phosphorylations. The inhibitory modulator may regulate cAMP-dependent protein kinase activity in cytosol and plasma membrane, and the stimulatory modulator for cGMP-dependent protein kinase may have a role in thyroid function independent of the cAMP-requiring system."}
{"id": "PMID:221202", "title": "The effect of hypophysectomy on rat chorionic somatomammotropin as measured by prolactin and growth hormone radioreceptor assays: possible significance in maintenance of somatomedin generation.", "content": "We have previously reported that serum somatomedin concentrations are maintained in pregnant rats after hypophysectomy. Because rat chorionic somatomammotropin (rCS) might replace pituitary GH during pregnancy, the concentration of rCS was measured at intervals after hypophysectomy on day of pregnancy. By day 16 of pregnancy, the serum rCS of hypophysectomized (hypox) rats was actually higher than that of normal pregnant rats when measured by a lactogenic radioreceptor assay. Increased levels of lactogenic radioreceptor activity (L-RRA) were maintained in the serum of hypox rats throughout the remainder of pregnancy. The GH radioreceptor activity (GH-RRA) of serum of hypox pregnant rats was also greater than that of normal rats during the last days of pregnancy, but the activity was only about 1/20th that of the L-RRA with the assays employed. There was no significant difference between placental L-RRA and GH-RRA of normal and hypox pregnant rats. The difference in concentration could not be attributed to differences in the number of fetuses. We conclude that the high levels of rCS were sufficient to maintain serum somatomedin concentration in hypox pregnant rats. This effect of rCS could have been due to binding by GH or PRL receptors of the maternal liver.", "contents": "The effect of hypophysectomy on rat chorionic somatomammotropin as measured by prolactin and growth hormone radioreceptor assays: possible significance in maintenance of somatomedin generation. We have previously reported that serum somatomedin concentrations are maintained in pregnant rats after hypophysectomy. Because rat chorionic somatomammotropin (rCS) might replace pituitary GH during pregnancy, the concentration of rCS was measured at intervals after hypophysectomy on day of pregnancy. By day 16 of pregnancy, the serum rCS of hypophysectomized (hypox) rats was actually higher than that of normal pregnant rats when measured by a lactogenic radioreceptor assay. Increased levels of lactogenic radioreceptor activity (L-RRA) were maintained in the serum of hypox rats throughout the remainder of pregnancy. The GH radioreceptor activity (GH-RRA) of serum of hypox pregnant rats was also greater than that of normal rats during the last days of pregnancy, but the activity was only about 1/20th that of the L-RRA with the assays employed. There was no significant difference between placental L-RRA and GH-RRA of normal and hypox pregnant rats. The difference in concentration could not be attributed to differences in the number of fetuses. We conclude that the high levels of rCS were sufficient to maintain serum somatomedin concentration in hypox pregnant rats. This effect of rCS could have been due to binding by GH or PRL receptors of the maternal liver."}
{"id": "PMID:221205", "title": "The effects of opiate agonist and antagonist on serum prolactin in primates: possible role for endorphins in prolactin regulation.", "content": "Intravenous administration of the opiate receptor antagonist naloxone produced a significant reduction in basal serum PRL concentrations in four male Macaca arctoides. Significant decreases from basal levels were found 15, 30, 45, 60, 90, 120, 150, and 180 min after the iv injection of 0.05 and 0.25 mg/kg naloxone. The iv administration of 0.4 mg/kg morphine produced rapid and significant increases in PRL levels, while 0.04 mg/kg morphine or saline produced no change. Both the dopamine receptor-stimulating agent apomorphine (0.15 mg/kg) and naloxone (0.25 mg/kg) decreased basal serum PRL and blocked the morphine-induced increases in serum PRL. These data support the hypothesis that endorphins are involved in the stimulation of PRL secretion.", "contents": "The effects of opiate agonist and antagonist on serum prolactin in primates: possible role for endorphins in prolactin regulation. Intravenous administration of the opiate receptor antagonist naloxone produced a significant reduction in basal serum PRL concentrations in four male Macaca arctoides. Significant decreases from basal levels were found 15, 30, 45, 60, 90, 120, 150, and 180 min after the iv injection of 0.05 and 0.25 mg/kg naloxone. The iv administration of 0.4 mg/kg morphine produced rapid and significant increases in PRL levels, while 0.04 mg/kg morphine or saline produced no change. Both the dopamine receptor-stimulating agent apomorphine (0.15 mg/kg) and naloxone (0.25 mg/kg) decreased basal serum PRL and blocked the morphine-induced increases in serum PRL. These data support the hypothesis that endorphins are involved in the stimulation of PRL secretion."}
{"id": "PMID:221210", "title": "Studies on adrenocorticotropic hormone receptor using isolated rat adrenocortical cells.", "content": "To clarify the function of ACTH receptors, the actions of ACTH on cyclic AMP formation, Ca2+-influx across cell membrane, and corticoidogenesis were examined using dispersed adrenocortical cells prepared from the rat adrenal gland. 1) There are two types of ACTH receptors from Scatchard analysis of 125I-ACTH1-24 binding to the cell, the one receptor is of high affinity and low capacity (dissociation constant (Kd1) = 2.6 x 10(-19) M and 7,350 sites per cell), and the other one is of low affinity and high capacity (dissociation constant (Kd2) = 7.1 x 10(-9)M and 57,400 sites per cell). 2) Both apparent dissociation constants derived from the effects of ACTH on corticoidogenesis and Ca2+ influx well correspond with Kd1 of the high affinity receptor, 3) Apparent dissociation constant obtained from the effect of ACTH on cyclic AMP formation is in good agreement with Kd2 of the low affinity receptor. Thus it could be deduced from these data that the high affinity receptor is concerned with an increased Ca2+-influx to regulate corticoidogenesis at physiological levels of ACTH, whereas the low affinity receptor is coupled to adenylate cyclase at supraphysiological concentrations of ACTH.", "contents": "Studies on adrenocorticotropic hormone receptor using isolated rat adrenocortical cells. To clarify the function of ACTH receptors, the actions of ACTH on cyclic AMP formation, Ca2+-influx across cell membrane, and corticoidogenesis were examined using dispersed adrenocortical cells prepared from the rat adrenal gland. 1) There are two types of ACTH receptors from Scatchard analysis of 125I-ACTH1-24 binding to the cell, the one receptor is of high affinity and low capacity (dissociation constant (Kd1) = 2.6 x 10(-19) M and 7,350 sites per cell), and the other one is of low affinity and high capacity (dissociation constant (Kd2) = 7.1 x 10(-9)M and 57,400 sites per cell). 2) Both apparent dissociation constants derived from the effects of ACTH on corticoidogenesis and Ca2+ influx well correspond with Kd1 of the high affinity receptor, 3) Apparent dissociation constant obtained from the effect of ACTH on cyclic AMP formation is in good agreement with Kd2 of the low affinity receptor. Thus it could be deduced from these data that the high affinity receptor is concerned with an increased Ca2+-influx to regulate corticoidogenesis at physiological levels of ACTH, whereas the low affinity receptor is coupled to adenylate cyclase at supraphysiological concentrations of ACTH."}
{"id": "PMID:221212", "title": "Long-term prognosis of patients with infantile spasms following ACTH therapy.", "content": "The influence of ACTH on the prognosis of patients with infantile spasms remains controversial. We have examined retrospectively the long-term benefits of initially successful ACTH therapy in patients treated at this institution between 1961 and 1974. Individuals with equivocal or minimal improvement during ACTH therapy were excluded from this study. Eighteen affected infants showed a favorable early response consisting of cessation of seizures for at least 3 weeks during ACTH therapy and concurrent disappearance of the hypsarhythmic EEG pattern. Modal age at last follow-up was 5 years (range, 15 months to 16 years). Infantile spasms recurred in 7 patients (39%), and 8 patients subsequently had other seizure types. All epileptiform (spike) activity disappeared from the EEGs of 8 patients during ACTH therapy, but in 4 of these cases epileptiform activity was present in later tracings. In the remaining 10 patients the hypsarhythmic pattern disappeared in association with ACTH therapy, but the EEG remained epileptiform (often only in sleep). Later EEGs were free of epileptiform activity in 5 of the 10 patients whose tracings contained spike discharges in the early follow-up period. Four patients (22%) were seizure free and without intellectual impairment when last evaluated.", "contents": "Long-term prognosis of patients with infantile spasms following ACTH therapy. The influence of ACTH on the prognosis of patients with infantile spasms remains controversial. We have examined retrospectively the long-term benefits of initially successful ACTH therapy in patients treated at this institution between 1961 and 1974. Individuals with equivocal or minimal improvement during ACTH therapy were excluded from this study. Eighteen affected infants showed a favorable early response consisting of cessation of seizures for at least 3 weeks during ACTH therapy and concurrent disappearance of the hypsarhythmic EEG pattern. Modal age at last follow-up was 5 years (range, 15 months to 16 years). Infantile spasms recurred in 7 patients (39%), and 8 patients subsequently had other seizure types. All epileptiform (spike) activity disappeared from the EEGs of 8 patients during ACTH therapy, but in 4 of these cases epileptiform activity was present in later tracings. In the remaining 10 patients the hypsarhythmic pattern disappeared in association with ACTH therapy, but the EEG remained epileptiform (often only in sleep). Later EEGs were free of epileptiform activity in 5 of the 10 patients whose tracings contained spike discharges in the early follow-up period. Four patients (22%) were seizure free and without intellectual impairment when last evaluated."}
{"id": "PMID:221214", "title": "Biological effects of raw and processed oil shale particles in the lungs of laboratory animals.", "content": "Environmental and occupational health concerns will have an effect on the developing oil shale technologies. The mining and crushing of large volumes of rock will be a characteristic of at least some of these technologies, and above ground disposal of proceessed shale will require adequate control measures. Exposure by inhalation to the dusts that may arise from shale oil technologies may present a hazard both in the work force and in the local population. Animal studies dealing with the effects of oil shale-related materials in the lung are in progress. Experiments involving Syrian hamsters exposed by inhalation and by intratracheal instillation are described.", "contents": "Biological effects of raw and processed oil shale particles in the lungs of laboratory animals. Environmental and occupational health concerns will have an effect on the developing oil shale technologies. The mining and crushing of large volumes of rock will be a characteristic of at least some of these technologies, and above ground disposal of proceessed shale will require adequate control measures. Exposure by inhalation to the dusts that may arise from shale oil technologies may present a hazard both in the work force and in the local population. Animal studies dealing with the effects of oil shale-related materials in the lung are in progress. Experiments involving Syrian hamsters exposed by inhalation and by intratracheal instillation are described."}
{"id": "PMID:221215", "title": "Morphological investigations of fibrogenic action of Estonian oil shale dust.", "content": "A review of morphological investigations carried out to clarify the pathogenicity of industrial dust produced in the mining and processing of Estonian oil shale is given. Histological examination of lungs of workers in the oil shale industry taken at necropsies showed that the inhalation of oil shale dust over a long period (more than 20 years) may cause the development of occupational pneumoconiotic changes in oil shale miners. The pneumoconiotic process develops slowly and is characterized by changes typical of the interstitial form of pneumoconiotic fibrosis in the lungs. Emphysematous changes and chronic bronchitis also occur. The average chemical content of oil shale as well as of samples of oil shale dust generated during mining and sorting procedures is given. The results of experiments in white rats are presented; these studies also indicate a mild fibrogenic action of Estonian oil shale dust.", "contents": "Morphological investigations of fibrogenic action of Estonian oil shale dust. A review of morphological investigations carried out to clarify the pathogenicity of industrial dust produced in the mining and processing of Estonian oil shale is given. Histological examination of lungs of workers in the oil shale industry taken at necropsies showed that the inhalation of oil shale dust over a long period (more than 20 years) may cause the development of occupational pneumoconiotic changes in oil shale miners. The pneumoconiotic process develops slowly and is characterized by changes typical of the interstitial form of pneumoconiotic fibrosis in the lungs. Emphysematous changes and chronic bronchitis also occur. The average chemical content of oil shale as well as of samples of oil shale dust generated during mining and sorting procedures is given. The results of experiments in white rats are presented; these studies also indicate a mild fibrogenic action of Estonian oil shale dust."}
{"id": "PMID:221216", "title": "Experimental approach to the determination of pulmonary carcinogenic influences of shale oil effluents.", "content": "Oil derived from oil shale deposits is known to contain many organic complexes. The formation of carcinogenic hydrocarbons is temperature-dependent and is associated with retorting of the oil. Furthermore, oil shale is a rich source of inorganic elements such as the metals. Biological studies have demonstrated that concentrated extract of tars from combustion of shale oil are carcingenic to the skin of mice. The purpose of the current project is to evaluate the potential carcinogenic hazard from inhalation of retort and combustion effluents for man. These studies will be carried out in pathogen-free rats by intratracheal instillation with and without added factors such supplemental particles and known carcinogens as interactants.", "contents": "Experimental approach to the determination of pulmonary carcinogenic influences of shale oil effluents. Oil derived from oil shale deposits is known to contain many organic complexes. The formation of carcinogenic hydrocarbons is temperature-dependent and is associated with retorting of the oil. Furthermore, oil shale is a rich source of inorganic elements such as the metals. Biological studies have demonstrated that concentrated extract of tars from combustion of shale oil are carcingenic to the skin of mice. The purpose of the current project is to evaluate the potential carcinogenic hazard from inhalation of retort and combustion effluents for man. These studies will be carried out in pathogen-free rats by intratracheal instillation with and without added factors such supplemental particles and known carcinogens as interactants."}
{"id": "PMID:221219", "title": "The 'enzyme-probe' method for characterizing metabolite pools. The use of NAD-glycohydrolase in human erythrocyte sonicate as a model system.", "content": "1. An approach for testing the homogeneity of metabolite pools is described. An alien enzyme that can attack the metabolite in question is introducted into the system studied. By analyzing the time-course of decomposition of the metabolite it can be decided whether the pool is homogeneous in respect of reactivity towards the probe-enzyme or can be divided into fractions of different reactivities. 2. The information obtainable from such experiments is illustrated by the case of human erythrocyte sonicate as model system with NAD-glycohydrolase as probe-enzyme. The nicotinamide adenine dinucleotide pool in the concentrated sonicate could be resolved into three fractions (I, II and III) with half-lives of about 1, 7 and 240 min, respectively. Fraction I is free NAD, fraction II is NAD bound to glyceraldehyde-3-phosphate dehydrogenase, and fraction III is coenzyme strongly bound to some, so far unidentified, protein. Sonicate glycolysis seems to require only fraction II and is unable to use fraction III under the experimental conditions applied. 3. The scope of application of the enzyme-probe method is discussed.", "contents": "The 'enzyme-probe' method for characterizing metabolite pools. The use of NAD-glycohydrolase in human erythrocyte sonicate as a model system. 1. An approach for testing the homogeneity of metabolite pools is described. An alien enzyme that can attack the metabolite in question is introducted into the system studied. By analyzing the time-course of decomposition of the metabolite it can be decided whether the pool is homogeneous in respect of reactivity towards the probe-enzyme or can be divided into fractions of different reactivities. 2. The information obtainable from such experiments is illustrated by the case of human erythrocyte sonicate as model system with NAD-glycohydrolase as probe-enzyme. The nicotinamide adenine dinucleotide pool in the concentrated sonicate could be resolved into three fractions (I, II and III) with half-lives of about 1, 7 and 240 min, respectively. Fraction I is free NAD, fraction II is NAD bound to glyceraldehyde-3-phosphate dehydrogenase, and fraction III is coenzyme strongly bound to some, so far unidentified, protein. Sonicate glycolysis seems to require only fraction II and is unable to use fraction III under the experimental conditions applied. 3. The scope of application of the enzyme-probe method is discussed."}
{"id": "PMID:221220", "title": "On the nature of biochemically generated hydroxyl radicals. Studies using the bleaching of p-nitrosodimethylaniline as a direct assay method.", "content": "An efficient scavenger for radiolytically generated hydroxyl (OH) radicals, p-nitrosodimethylaniline, was used to try to substantiate the presence of this oxygen radical species in several biochemical systems. Most of these systems which were investigated had previously been assumed to generate OH radicals, e.g. the autoxidation of 6-hydroxydopamine, the hydroxylating system NADH/phenazine methosulfate, and the oxidation of xanthine or acetaldehyde by xanthine oxidase. We did not observe inhibition of the bleaching of p-nitrosodimethylaniline in oxygenated solutions by other scavengers of OH radicals nor, in the case of xanthine/xanthine oxidase, by catalase and superoxide dismutase. We therefore conclude that, under biochemical conditions as opposed to radiolysis or photolysis, no freely diffusable OH radicals are formed. Rather, a strongly oxidizing OH-analogous complex is considered to represent the p-nitrosodimethylaniline-detectable species formed under these conditions.", "contents": "On the nature of biochemically generated hydroxyl radicals. Studies using the bleaching of p-nitrosodimethylaniline as a direct assay method. An efficient scavenger for radiolytically generated hydroxyl (OH) radicals, p-nitrosodimethylaniline, was used to try to substantiate the presence of this oxygen radical species in several biochemical systems. Most of these systems which were investigated had previously been assumed to generate OH radicals, e.g. the autoxidation of 6-hydroxydopamine, the hydroxylating system NADH/phenazine methosulfate, and the oxidation of xanthine or acetaldehyde by xanthine oxidase. We did not observe inhibition of the bleaching of p-nitrosodimethylaniline in oxygenated solutions by other scavengers of OH radicals nor, in the case of xanthine/xanthine oxidase, by catalase and superoxide dismutase. We therefore conclude that, under biochemical conditions as opposed to radiolysis or photolysis, no freely diffusable OH radicals are formed. Rather, a strongly oxidizing OH-analogous complex is considered to represent the p-nitrosodimethylaniline-detectable species formed under these conditions."}
{"id": "PMID:221221", "title": "Structure of the disaccharide chain of galactosyl-N-acetylgalactosaminyl-protein synthesized in vitro.", "content": "In order to obtain a [14C]galactosyl-N-acetylgalactosaminyl-protein which would be useful as an acceptor in studies on the specificity of glycosyltransferases, a porcine submaxillary gland microsomal galactosyltransferase preparation was used for the galactosylation in vitro of N-acetylgalactosaminyl-protein (desialylated ovine submaxillary mucin). The newly formed oligosaccharide unit was obtained as a reduced disaccharide after alkaline borohydride treatment of the [14C]galactosyl-N-acetylgalactosaminyl-protein product and as glycopeptides by proteolytic digestion of the glycoprotein. The reduced disaccharide consisted of equimolar amounts of galactose and N-acetylgalactosaminitol and was characterized by thin-layer chromatography, high-voltage electrophoresis and gas-liquid chromatography. Periodate oxidation studies on the reduced disaccharide revealed that [14C]galactose was linked to position C-3 on the N-acetylgalactosaminyl residue. Digestion of the reduced disaccharide and the glycopeptides with galactosidases gave equivocal results as to the anomeric configuration of the [14C]galactose residue. Nuclear magnetic resonance of the reduced disaccharide, however, definitely indicated that the configuration was beta. The specificity of the porcine submaxillary gland galactosyltransferase thus can be defined as a uridine diphosphogalactose: alpha-D-N-acetylgalactosaminyl-protein beta 1 leads to 3 transferase activity.", "contents": "Structure of the disaccharide chain of galactosyl-N-acetylgalactosaminyl-protein synthesized in vitro. In order to obtain a [14C]galactosyl-N-acetylgalactosaminyl-protein which would be useful as an acceptor in studies on the specificity of glycosyltransferases, a porcine submaxillary gland microsomal galactosyltransferase preparation was used for the galactosylation in vitro of N-acetylgalactosaminyl-protein (desialylated ovine submaxillary mucin). The newly formed oligosaccharide unit was obtained as a reduced disaccharide after alkaline borohydride treatment of the [14C]galactosyl-N-acetylgalactosaminyl-protein product and as glycopeptides by proteolytic digestion of the glycoprotein. The reduced disaccharide consisted of equimolar amounts of galactose and N-acetylgalactosaminitol and was characterized by thin-layer chromatography, high-voltage electrophoresis and gas-liquid chromatography. Periodate oxidation studies on the reduced disaccharide revealed that [14C]galactose was linked to position C-3 on the N-acetylgalactosaminyl residue. Digestion of the reduced disaccharide and the glycopeptides with galactosidases gave equivocal results as to the anomeric configuration of the [14C]galactose residue. Nuclear magnetic resonance of the reduced disaccharide, however, definitely indicated that the configuration was beta. The specificity of the porcine submaxillary gland galactosyltransferase thus can be defined as a uridine diphosphogalactose: alpha-D-N-acetylgalactosaminyl-protein beta 1 leads to 3 transferase activity."}
{"id": "PMID:221224", "title": "Cell-mediated immunity to antigens associated with murine sarcoma virus-induced tumors: augmentation of cytolytic T lymphocyte activity by successive specific and nonspecific stimulation in vitro.", "content": "It has been shown previously that lymphoid cells from mice which have rejected a tumor induced by the Moloney sarcoma virus-leukemia virus (MSV-MLV) complex develop high levels of specific H-2-restricted cytolytic T lymphocyte (CTL) activity after in vitro stimulation with syngeneic, irradiated MLV-induced lymphoma cells in mixed leukocyte-tumor cell cultures (MLTC). Attempts to further increase lytic activity by restimulating long-term MLTC cells with syngeneic, irradiated lymphoma cells have met but with limited success. This report shows that, in contrast to the lack of increased activity observed after specific stimulation with lymphoma cells, nonspecific stimulation of long-term MLTC cells either with supernatants from secondary mixed leukocyte cultures (2 degrees MLC SN) or with supernatants from concanavalin A-stimulated spleen cells leads, on a per cell basis, to a further 5 to 10-fold increase in CTL activity. The stimulatory activity of 2 degrees MLC SN is due to a factor(s) of apparent mol. wt. of 25,000 to 40,000. The activity of the CTL populations formed under these conditions is at least 100-fold higher against syngeneic as compared to allogeneic MLV-induced or unrelated tumor cells.", "contents": "Cell-mediated immunity to antigens associated with murine sarcoma virus-induced tumors: augmentation of cytolytic T lymphocyte activity by successive specific and nonspecific stimulation in vitro. It has been shown previously that lymphoid cells from mice which have rejected a tumor induced by the Moloney sarcoma virus-leukemia virus (MSV-MLV) complex develop high levels of specific H-2-restricted cytolytic T lymphocyte (CTL) activity after in vitro stimulation with syngeneic, irradiated MLV-induced lymphoma cells in mixed leukocyte-tumor cell cultures (MLTC). Attempts to further increase lytic activity by restimulating long-term MLTC cells with syngeneic, irradiated lymphoma cells have met but with limited success. This report shows that, in contrast to the lack of increased activity observed after specific stimulation with lymphoma cells, nonspecific stimulation of long-term MLTC cells either with supernatants from secondary mixed leukocyte cultures (2 degrees MLC SN) or with supernatants from concanavalin A-stimulated spleen cells leads, on a per cell basis, to a further 5 to 10-fold increase in CTL activity. The stimulatory activity of 2 degrees MLC SN is due to a factor(s) of apparent mol. wt. of 25,000 to 40,000. The activity of the CTL populations formed under these conditions is at least 100-fold higher against syngeneic as compared to allogeneic MLV-induced or unrelated tumor cells."}
{"id": "PMID:221229", "title": "Changes in the fibroblastoid colony forming unit population from mouse bone marrow in early stages of Soule virus induced murine leukemia.", "content": "Fibroblastoid cells from mouse bone marrow belong to the hemopoietic inductive microenvironment involved in the regulation of hemopoiesis (1). We observed a decline in the incidence of precursors of these cells (fibroblastoid colony forming units) in the early stages of viral leukemogenesis. This was not accompanied by similar changes in bone marrow derived hemopoietic colony forming cell populations (CFU-s and CFU-c). Cultured fibroblastoid colonies from the bone marrow of young AKR mice or Soule murine leukemia virus inoculated BALB/c mice were found to produce type-C ecotropic virus. No such production was observed when similarly cultured granulocyte macrophage colonies (CFU-c) from the bone marrow of these mice were examined. The possibility that the fibroblastoid cell population is a major source of ecotropic leukemia viruses in the early stages of viral leukemogenesis is discussed.", "contents": "Changes in the fibroblastoid colony forming unit population from mouse bone marrow in early stages of Soule virus induced murine leukemia. Fibroblastoid cells from mouse bone marrow belong to the hemopoietic inductive microenvironment involved in the regulation of hemopoiesis (1). We observed a decline in the incidence of precursors of these cells (fibroblastoid colony forming units) in the early stages of viral leukemogenesis. This was not accompanied by similar changes in bone marrow derived hemopoietic colony forming cell populations (CFU-s and CFU-c). Cultured fibroblastoid colonies from the bone marrow of young AKR mice or Soule murine leukemia virus inoculated BALB/c mice were found to produce type-C ecotropic virus. No such production was observed when similarly cultured granulocyte macrophage colonies (CFU-c) from the bone marrow of these mice were examined. The possibility that the fibroblastoid cell population is a major source of ecotropic leukemia viruses in the early stages of viral leukemogenesis is discussed."}
{"id": "PMID:221233", "title": "Seasonal variation of androgen interconversion in testicular tissue of Rana temporaria in vitro.", "content": "Testicular steroid metabolism of winter and spring frogs, Rana temporaria, were studied by in vitro incubation with radioactively labelled dehydroepiandrosterone and androst-4-ene-3,17-dione. Marked seasonal differences were observed which are in line with the findings of others.", "contents": "Seasonal variation of androgen interconversion in testicular tissue of Rana temporaria in vitro. Testicular steroid metabolism of winter and spring frogs, Rana temporaria, were studied by in vitro incubation with radioactively labelled dehydroepiandrosterone and androst-4-ene-3,17-dione. Marked seasonal differences were observed which are in line with the findings of others."}
{"id": "PMID:221234", "title": "Increase of interferon antiviral activity by exogenous cyclic adenosine-3':5'-monophosphate (cAMP).", "content": "Some effects of cAMP on replication of Semliki Forest Virus in chick embryo fibroblast cell cultures are described. Depending on concentration, the incorporation of [3H]-uridine into viral RNA or the formation of plaque-forming units is inhibited; the highest concentration tested was 8 mM. Cyclic AMP has an effect of its own and increases the Interferon action in the lower concentration ranges of Interferon (up to 1 unit/ml). The effect of cyclic AMP is fast, needs no induction and is also visible in late phases of viral replication. However, these experiments do not establish a causal relation between cAMP and Interferon.", "contents": "Increase of interferon antiviral activity by exogenous cyclic adenosine-3':5'-monophosphate (cAMP). Some effects of cAMP on replication of Semliki Forest Virus in chick embryo fibroblast cell cultures are described. Depending on concentration, the incorporation of [3H]-uridine into viral RNA or the formation of plaque-forming units is inhibited; the highest concentration tested was 8 mM. Cyclic AMP has an effect of its own and increases the Interferon action in the lower concentration ranges of Interferon (up to 1 unit/ml). The effect of cyclic AMP is fast, needs no induction and is also visible in late phases of viral replication. However, these experiments do not establish a causal relation between cAMP and Interferon."}
{"id": "PMID:221235", "title": "Functional consequences of treating turkey liver fructose-1,6-bisphosphatase with penicillin G.", "content": "Treatment of turkey liver fructose-1,6--bisphosphatase with penicillin G progressively inactivated the enzyme and desensitized the enzyme toward high substrate inhibition. The treatment also led to reduced sensitivity to AMP inhibition and the loss of cooperative interaction among AMP-binding sites. These altered properties were not reversed by dialysis, but were prevented when treatment with penicillin G was perfomed in the presence of substrate.", "contents": "Functional consequences of treating turkey liver fructose-1,6-bisphosphatase with penicillin G. Treatment of turkey liver fructose-1,6--bisphosphatase with penicillin G progressively inactivated the enzyme and desensitized the enzyme toward high substrate inhibition. The treatment also led to reduced sensitivity to AMP inhibition and the loss of cooperative interaction among AMP-binding sites. These altered properties were not reversed by dialysis, but were prevented when treatment with penicillin G was perfomed in the presence of substrate."}
{"id": "PMID:221236", "title": "Effects of insulin on plasma fibrinogen levels in rats submitted to tissue injury or ACTH administration.", "content": "Insulin is necessary to produce an increase of plasma fibrinogen in rats submitted to tissue injury or ACTH administration. This increase is more significant when endogenous or exogenous excess of insulin is present, while in uninjured rats the absence or excess insulin does not modify plasma fibrinogen.", "contents": "Effects of insulin on plasma fibrinogen levels in rats submitted to tissue injury or ACTH administration. Insulin is necessary to produce an increase of plasma fibrinogen in rats submitted to tissue injury or ACTH administration. This increase is more significant when endogenous or exogenous excess of insulin is present, while in uninjured rats the absence or excess insulin does not modify plasma fibrinogen."}
{"id": "PMID:221237", "title": "Cytotoxicity of ethyl methanesulfonate in mice spermatogonia.", "content": "Enumeration of different types of spermatogonia, following a single i.p. administration of different doses of ethyl methanesulfonate in mice, showed a survival of A1-A4 and in spermatogonia is markedly reduced due to cell killing while the remaining types of spermatogonia were affected marginally. The cell killing effect was dose-dependent, and replenishment of these cells was observed by the end of one cycle of the seminiferous epithelium comprising of 8.5 days.", "contents": "Cytotoxicity of ethyl methanesulfonate in mice spermatogonia. Enumeration of different types of spermatogonia, following a single i.p. administration of different doses of ethyl methanesulfonate in mice, showed a survival of A1-A4 and in spermatogonia is markedly reduced due to cell killing while the remaining types of spermatogonia were affected marginally. The cell killing effect was dose-dependent, and replenishment of these cells was observed by the end of one cycle of the seminiferous epithelium comprising of 8.5 days."}
{"id": "PMID:221239", "title": "On the effects of thiamphenicol and chloramphenicol on nucleic acid and protein synthesis in rabbit bone marrow cells in vivo and in vitro.", "content": "Besides the in vivo effects of thiamphenicol (TAP), this study shows the in vitro effects of TAP and D- and L-threo-chloramphenicol (CAP) on the synthesis of DNA, RNA, protein and hemoglobin in marrow cells and reticulocytes. The experiments make it likely that TAP exerts its action on a stem cell in a proliferating phase.", "contents": "On the effects of thiamphenicol and chloramphenicol on nucleic acid and protein synthesis in rabbit bone marrow cells in vivo and in vitro. Besides the in vivo effects of thiamphenicol (TAP), this study shows the in vitro effects of TAP and D- and L-threo-chloramphenicol (CAP) on the synthesis of DNA, RNA, protein and hemoglobin in marrow cells and reticulocytes. The experiments make it likely that TAP exerts its action on a stem cell in a proliferating phase."}
{"id": "PMID:221243", "title": "[Evaluation of the pharmacological properties of a new steroid curarelike agent, RGH 1106].", "content": "Tests on cats showed the compound RGH 1106 to possess an antidepolarizing mechanism of action. The sequence of myorelaxation, arising under the effect of this agent, is characterized by relaxation in the first place of the musculus masseter, muscles of limbs, then of abdominal muscles and those of the diaphragm and, finally, of the intercostal muscles. RGH 1106 doses not possess cardiotropic m-cholinolytic action, does not exert a ganglion blocking effect, nor affects the central nervous system. It neither changes the blood supply of the myocardium and the uptake of oxygen by the latter, nor inhibits the acetylcholinesterase.", "contents": "[Evaluation of the pharmacological properties of a new steroid curarelike agent, RGH 1106]. Tests on cats showed the compound RGH 1106 to possess an antidepolarizing mechanism of action. The sequence of myorelaxation, arising under the effect of this agent, is characterized by relaxation in the first place of the musculus masseter, muscles of limbs, then of abdominal muscles and those of the diaphragm and, finally, of the intercostal muscles. RGH 1106 doses not possess cardiotropic m-cholinolytic action, does not exert a ganglion blocking effect, nor affects the central nervous system. It neither changes the blood supply of the myocardium and the uptake of oxygen by the latter, nor inhibits the acetylcholinesterase."}
{"id": "PMID:221244", "title": "[Effect of aggregation inducers and inhibitors on the pentosephosphate pathway enzymes of glucose conversion in the thrombocytes].", "content": "Experiments with rabbit platelets in vitro revealed differences in the effect of the aggregation inducers (ADP and thrombin) and the aggregation inhibitor cyclic AMP on the activity of the enzymes of pentosephosphate pathway of glucose oxidation. ADP and thrombin decrease significantly the activity of glucoso-6-phosphate dehydrogenase (G-6-PDH) and riboso-5-phosphate-metabolizing enzymes (R-5-PME) in platelets during aggregation, whereas cyclic AMP produces no appreciable effect on the G-6-PDH activity, but increases significantly the R-5-PME activity. ADP decreases and cyclic AMP raises substantially the activity of R-5-PME. The differences were also revealed in the effects produced by cyclic AMP and cyclic GMP on the enzymes of pentosephosphate pathway of glucose oxidation. Unlike cyclic AMP, cyclic GMP decreased significantly the activity of G-6-PDH. The activity of R-5-PME and cyclic GMP transketolase was more pronounced than that of cyclic AMP. Like cyclic AMP, cyclic GMP differs from ADP and thrombin in the action produced on the enzymes of pentosephosphate pathway of glucose oxidation.", "contents": "[Effect of aggregation inducers and inhibitors on the pentosephosphate pathway enzymes of glucose conversion in the thrombocytes]. Experiments with rabbit platelets in vitro revealed differences in the effect of the aggregation inducers (ADP and thrombin) and the aggregation inhibitor cyclic AMP on the activity of the enzymes of pentosephosphate pathway of glucose oxidation. ADP and thrombin decrease significantly the activity of glucoso-6-phosphate dehydrogenase (G-6-PDH) and riboso-5-phosphate-metabolizing enzymes (R-5-PME) in platelets during aggregation, whereas cyclic AMP produces no appreciable effect on the G-6-PDH activity, but increases significantly the R-5-PME activity. ADP decreases and cyclic AMP raises substantially the activity of R-5-PME. The differences were also revealed in the effects produced by cyclic AMP and cyclic GMP on the enzymes of pentosephosphate pathway of glucose oxidation. Unlike cyclic AMP, cyclic GMP decreased significantly the activity of G-6-PDH. The activity of R-5-PME and cyclic GMP transketolase was more pronounced than that of cyclic AMP. Like cyclic AMP, cyclic GMP differs from ADP and thrombin in the action produced on the enzymes of pentosephosphate pathway of glucose oxidation."}
{"id": "PMID:221268", "title": "Long-lasting synaptic potentials and the modulation of synaptic transmission.", "content": "Long-lasting postsynaptic potentials (PSPs) generated by decreases in membrane conductance (permeability) have been reported in many types of neurons. We investigated the possible role of such long-lasting decreases in membrane conductance in the modulation of synaptic transmission in the sympathetic ganglion of the bullfrog. The molecular basis by which such conductance-decrease PSPs are generated was also investigated. Synaptic activation of muscarinic cholinergic receptors on these sympathetic neurons results in the generation of a slow EPSP (excitatory postsynaptic potential), which is accompanied by a decrease in membrane conductance. We found that the conventional \"fast\" EPSPs were increased in amplitude and duration during the iontophoretic application of methacholine, which activates the muscarinic postsynaptic receptors. A similar result was obtained when a noncholinergic conductance-decrease PSP--the late-slow EPSP--was elicited by stimulation of a separate synaptic pathway. The enhancement of fast EPSP amplitude increased the probability of postsynaptic action potential generation, thus increasing the efficacy of impulse transmission across the synapse. Stimulation of one synaptic pathway is therefore capable of increasing the efficacy of synaptic transmission in a second synaptic pathway by a postsynaptic mechanism. Furthermore, this enhancement of synaptic efficacy is long-lasting by virtue of the long duration of the slow PSP. Biochemical and electrophysiological techniques were used to investigate whether cyclic nucleotides are intracellular second messengers mediating the membrane permeability changes underlying slow-PSP generation. Stimulation of the synaptic inputs, which lead to the generation of the slow-PSPs, increased the ganglionic content of both cyclic AMP and cyclic GMP. However, electrophysiological analysis of the actions of these cyclic nucleotides and the actions of agents that affect their metabolism does not provide support for such a second messenger role for either cyclic nucleotide.", "contents": "Long-lasting synaptic potentials and the modulation of synaptic transmission. Long-lasting postsynaptic potentials (PSPs) generated by decreases in membrane conductance (permeability) have been reported in many types of neurons. We investigated the possible role of such long-lasting decreases in membrane conductance in the modulation of synaptic transmission in the sympathetic ganglion of the bullfrog. The molecular basis by which such conductance-decrease PSPs are generated was also investigated. Synaptic activation of muscarinic cholinergic receptors on these sympathetic neurons results in the generation of a slow EPSP (excitatory postsynaptic potential), which is accompanied by a decrease in membrane conductance. We found that the conventional \"fast\" EPSPs were increased in amplitude and duration during the iontophoretic application of methacholine, which activates the muscarinic postsynaptic receptors. A similar result was obtained when a noncholinergic conductance-decrease PSP--the late-slow EPSP--was elicited by stimulation of a separate synaptic pathway. The enhancement of fast EPSP amplitude increased the probability of postsynaptic action potential generation, thus increasing the efficacy of impulse transmission across the synapse. Stimulation of one synaptic pathway is therefore capable of increasing the efficacy of synaptic transmission in a second synaptic pathway by a postsynaptic mechanism. Furthermore, this enhancement of synaptic efficacy is long-lasting by virtue of the long duration of the slow PSP. Biochemical and electrophysiological techniques were used to investigate whether cyclic nucleotides are intracellular second messengers mediating the membrane permeability changes underlying slow-PSP generation. Stimulation of the synaptic inputs, which lead to the generation of the slow-PSPs, increased the ganglionic content of both cyclic AMP and cyclic GMP. However, electrophysiological analysis of the actions of these cyclic nucleotides and the actions of agents that affect their metabolism does not provide support for such a second messenger role for either cyclic nucleotide."}
{"id": "PMID:221269", "title": "Functional role of serotonergic neuromodulation in Aplysia.", "content": "The serotonergic metacerebral cell (MCC) of the mollusk Aplysia produces slow synaptic potentials in motor neurons of the buccal muscle, and increases the rate of ongoing rhythmic burst output of the buccal ganglion. In addition, the MCC acts peripherally to enhance the strength of buccal muscle contractions that are produced by firing of motor neurons. The potentiation of contraction is not associated with any detectable changes of resting membrane potential of muscle cells. Although MCC activity produces a small enhancement of excitatory junctional potentials, several experiments clearly indicate that the MCC has a direct potentiating effect on excitation-contraction coupling. The data suggest that potentiation of contraction might be mediated by cAMP. For example, activity of the MCC enchances the rate of accumulation of cAMP in buccal muscle, application of phosphodiesterase resistant analogs of cAMP potentiates muscle contraction, and a phosphodiesterase inhibitor enhances the effect of MCC stimulation. Recordings from free-moving animals indicate that the MCC becomes activated by exposure of the animal to food stimuli, and that the activation parallels the presence of a food-arousal state. Food-arousal is characterized by enhanced strength and increased frequency of biting responses. Both these effects can result from activity of the MCC. Thus, in this system, modulatory synaptic actions function to provide the substrate for a type behavioral modulation.", "contents": "Functional role of serotonergic neuromodulation in Aplysia. The serotonergic metacerebral cell (MCC) of the mollusk Aplysia produces slow synaptic potentials in motor neurons of the buccal muscle, and increases the rate of ongoing rhythmic burst output of the buccal ganglion. In addition, the MCC acts peripherally to enhance the strength of buccal muscle contractions that are produced by firing of motor neurons. The potentiation of contraction is not associated with any detectable changes of resting membrane potential of muscle cells. Although MCC activity produces a small enhancement of excitatory junctional potentials, several experiments clearly indicate that the MCC has a direct potentiating effect on excitation-contraction coupling. The data suggest that potentiation of contraction might be mediated by cAMP. For example, activity of the MCC enchances the rate of accumulation of cAMP in buccal muscle, application of phosphodiesterase resistant analogs of cAMP potentiates muscle contraction, and a phosphodiesterase inhibitor enhances the effect of MCC stimulation. Recordings from free-moving animals indicate that the MCC becomes activated by exposure of the animal to food stimuli, and that the activation parallels the presence of a food-arousal state. Food-arousal is characterized by enhanced strength and increased frequency of biting responses. Both these effects can result from activity of the MCC. Thus, in this system, modulatory synaptic actions function to provide the substrate for a type behavioral modulation."}
{"id": "PMID:221271", "title": "The role of sodium transport in thyroid thermogenesis.", "content": "The hypothesis that augmentation of Na+ transport activity mediates a significant fraction of thyroid thermogenesis is supported by studies on a wide range of target tissues. Recent criticisms based on theoretical and experimental considerations do not appear to negate the validity of this concept. A basic difficulty that remains to be resolved, however, is the development of techniques for assessing the contribution of the Na+ transport pathway to energy turnover in the intact animal.", "contents": "The role of sodium transport in thyroid thermogenesis. The hypothesis that augmentation of Na+ transport activity mediates a significant fraction of thyroid thermogenesis is supported by studies on a wide range of target tissues. Recent criticisms based on theoretical and experimental considerations do not appear to negate the validity of this concept. A basic difficulty that remains to be resolved, however, is the development of techniques for assessing the contribution of the Na+ transport pathway to energy turnover in the intact animal."}
{"id": "PMID:221273", "title": "Cellular events underlying catecholamine-induced thermogenesis: cation transport in brown adipocytes.", "content": "Evidence supporting the hypothesis that the active transport of Na+ and K+ contributes significantly to catecholamine-mediated brown fat thermogenesis is reviewed. Such evidence indicates that the Na+/K+ membrane pump is activated following norepinephrine interaction with alpha- and beta-adrenergic membrane receptors. That the involvement of the pump in the thermogenic response is considerable is indicated by the finding that pump inhibition is accompanied by a 50--70% reduction of the catecholamine-evoked respiratory stimulation of isolated hamster brown adipocytes. This inhibitory effect of pump blockade suggests that in the norepinephrine-activated brown adipocyte, the pump generates a stimulatory signal for pathways of substrate oxidation, the operation of these being associated with conversion of chemical energy to heat.", "contents": "Cellular events underlying catecholamine-induced thermogenesis: cation transport in brown adipocytes. Evidence supporting the hypothesis that the active transport of Na+ and K+ contributes significantly to catecholamine-mediated brown fat thermogenesis is reviewed. Such evidence indicates that the Na+/K+ membrane pump is activated following norepinephrine interaction with alpha- and beta-adrenergic membrane receptors. That the involvement of the pump in the thermogenic response is considerable is indicated by the finding that pump inhibition is accompanied by a 50--70% reduction of the catecholamine-evoked respiratory stimulation of isolated hamster brown adipocytes. This inhibitory effect of pump blockade suggests that in the norepinephrine-activated brown adipocyte, the pump generates a stimulatory signal for pathways of substrate oxidation, the operation of these being associated with conversion of chemical energy to heat."}
{"id": "PMID:221274", "title": "Cyclic nucleotides and neuromuscular transmission.", "content": "A review of the research on cyclic nucleotides and neuromuscular transmission suggests that cAMP is involved in the release of transmitter from motor nerve endings. Lipid-soluble derivations of cAMP cause depolarization of unstimulated nerve endings and prolong the after potentials of stimulated nerve endings. They also increase the frequency of miniature end plate potentials and increase the quantal content of stimulus evoked end plate potentials. Similar effects are produced by compounds that activate adenylate cyclase or inhibit phosphodiesterase. The responses to the derivatives of cAMP and activators of cyclase are enhanced by inhibitors of phosphodiesterase and prevented by compounds that block the flux of calcium into nerve endings. There is no evidence that suggests that cyclic nucleotides are involved in the postjunctional response to transmitter. Thus, it seems likely that cAMP is involved in the regulation of calcium in motor nerve endings and the exocytosis of transmitter. Additional study should expand our knowledge of neuromuscular transmission and contribute to an understanding of the functions of cyclic nucleotides in other synapses.", "contents": "Cyclic nucleotides and neuromuscular transmission. A review of the research on cyclic nucleotides and neuromuscular transmission suggests that cAMP is involved in the release of transmitter from motor nerve endings. Lipid-soluble derivations of cAMP cause depolarization of unstimulated nerve endings and prolong the after potentials of stimulated nerve endings. They also increase the frequency of miniature end plate potentials and increase the quantal content of stimulus evoked end plate potentials. Similar effects are produced by compounds that activate adenylate cyclase or inhibit phosphodiesterase. The responses to the derivatives of cAMP and activators of cyclase are enhanced by inhibitors of phosphodiesterase and prevented by compounds that block the flux of calcium into nerve endings. There is no evidence that suggests that cyclic nucleotides are involved in the postjunctional response to transmitter. Thus, it seems likely that cAMP is involved in the regulation of calcium in motor nerve endings and the exocytosis of transmitter. Additional study should expand our knowledge of neuromuscular transmission and contribute to an understanding of the functions of cyclic nucleotides in other synapses."}
{"id": "PMID:221275", "title": "Cyclic nucleotides in central synaptic function.", "content": "A wide array of interdisciplinary experiments have served to strengthen the general premise that some central synaptic effects of neurotransmitters may be mediated by cyclic nucleotides. Specific instances of such second messenger mediation are most strongly supported for certain noradrenergic connections of the locus coeruleus (LC) and for dopaminergic connections within the caudate nucleus. In these sites catecholamines selectively activate intraneuronal cyclic AMP synthesis, and exogenously applied cyclic AMP closely mimics the biophysical actions of the catecholamine on target neurons. In cerebellar cortex, iontophoresis of norepinephrine, stimulation of LC, or iontophoresis of cyclic AMP lead to hyperpolarization and increased membrane resistance. Although overtly inhibitory when examined in isolation, the effects of the LC system coupled to adenylate cyclase can initiate a holistic set of target cell responses which can enhance or \"enable\" the actions of other synaptic inputs to the target cells. Electrophysiologic and immunocytochemical evidence suggests that this heterosynaptic interaction may arise from phosphorylation of the synaptic membrane substrate of cyclic AMP-dependent protein kinase, or Protein 1.", "contents": "Cyclic nucleotides in central synaptic function. A wide array of interdisciplinary experiments have served to strengthen the general premise that some central synaptic effects of neurotransmitters may be mediated by cyclic nucleotides. Specific instances of such second messenger mediation are most strongly supported for certain noradrenergic connections of the locus coeruleus (LC) and for dopaminergic connections within the caudate nucleus. In these sites catecholamines selectively activate intraneuronal cyclic AMP synthesis, and exogenously applied cyclic AMP closely mimics the biophysical actions of the catecholamine on target neurons. In cerebellar cortex, iontophoresis of norepinephrine, stimulation of LC, or iontophoresis of cyclic AMP lead to hyperpolarization and increased membrane resistance. Although overtly inhibitory when examined in isolation, the effects of the LC system coupled to adenylate cyclase can initiate a holistic set of target cell responses which can enhance or \"enable\" the actions of other synaptic inputs to the target cells. Electrophysiologic and immunocytochemical evidence suggests that this heterosynaptic interaction may arise from phosphorylation of the synaptic membrane substrate of cyclic AMP-dependent protein kinase, or Protein 1."}
{"id": "PMID:221276", "title": "Toxic substances and cell membrane function.", "content": "The exposed location and functional importance of cell membranes make them particularly susceptible to the toxic effects of many chemicals. The likelihood of such effects has been appreciated for many years. However, the recent advent of new techniques has greatly increased our understanding of the complexities of membrane structure and function. These data make it quite clear that the interaction of toxic compounds with either the protein or the lipid component of cell membranes may substantially alter membrane function. This paper summarizes the current concepts of membrane structure and function and discusses the techniques currently in use to study cell membranes. Several examples are presented in which xenobiotics significantly alter membrane function. These include effects of heavy metals on passive ion permeability, impairment of osmoregulation and calcium transport by organochlorine pesticides, inhibition of the transport of neurotransmitter metabolites by phenoxyacetic acid herbicides in choroid plexus, and reduction in intestinal nutrient transport by heavy metals. Hence the study of the interactions of foreign compounds with membrane function may enhance our understanding of mechanisms both of toxicity and of basic membrane function.", "contents": "Toxic substances and cell membrane function. The exposed location and functional importance of cell membranes make them particularly susceptible to the toxic effects of many chemicals. The likelihood of such effects has been appreciated for many years. However, the recent advent of new techniques has greatly increased our understanding of the complexities of membrane structure and function. These data make it quite clear that the interaction of toxic compounds with either the protein or the lipid component of cell membranes may substantially alter membrane function. This paper summarizes the current concepts of membrane structure and function and discusses the techniques currently in use to study cell membranes. Several examples are presented in which xenobiotics significantly alter membrane function. These include effects of heavy metals on passive ion permeability, impairment of osmoregulation and calcium transport by organochlorine pesticides, inhibition of the transport of neurotransmitter metabolites by phenoxyacetic acid herbicides in choroid plexus, and reduction in intestinal nutrient transport by heavy metals. Hence the study of the interactions of foreign compounds with membrane function may enhance our understanding of mechanisms both of toxicity and of basic membrane function."}
{"id": "PMID:221277", "title": "Effect of prolactin on the calcium binding and/or transport of ejaculated and epididymal human spermatozoa.", "content": "The prolactin concentration in human seminal plasma and in human epididymal cauda fluid was assessed by radioimmunoassay. The prolactin concentration in cauda plasma was found to be similar to that found in male blood serum (5.5 to 9.1 ng/ml) and significantly lower than the concentration of the hormone found in seminal plasma obtained either from euspermic (48 +/- 12 ng/ml) or from vasectomized volunteers (50 +/- 10.2 ng/ml) (P less than 0.001). Calcium binding and/or transport in ejaculated spermatozoa were found to be little (0.29 +/- 0.08 nmoles/10(8) cells) and dependent on a quickly saturable process. The addition of 200 ng of human prolactin/ml induced a 60% increase in this parameter, while 50 ng of prolactin/ml were ineffective. Epididymal human spermatozoa differ from ejaculated sperm cells in showing greater, time-dependent, calcium binding and/or transport under basal conditions (2.00 +/- 0.35 nmoles/10(8) cells/hour), and in being more susceptible to the stimulating action of prolactin (4.4 +/- 0.68 nmoles/10(8) cells/hour in the presence of 50 ng of prolactin/ml).", "contents": "Effect of prolactin on the calcium binding and/or transport of ejaculated and epididymal human spermatozoa. The prolactin concentration in human seminal plasma and in human epididymal cauda fluid was assessed by radioimmunoassay. The prolactin concentration in cauda plasma was found to be similar to that found in male blood serum (5.5 to 9.1 ng/ml) and significantly lower than the concentration of the hormone found in seminal plasma obtained either from euspermic (48 +/- 12 ng/ml) or from vasectomized volunteers (50 +/- 10.2 ng/ml) (P less than 0.001). Calcium binding and/or transport in ejaculated spermatozoa were found to be little (0.29 +/- 0.08 nmoles/10(8) cells) and dependent on a quickly saturable process. The addition of 200 ng of human prolactin/ml induced a 60% increase in this parameter, while 50 ng of prolactin/ml were ineffective. Epididymal human spermatozoa differ from ejaculated sperm cells in showing greater, time-dependent, calcium binding and/or transport under basal conditions (2.00 +/- 0.35 nmoles/10(8) cells/hour), and in being more susceptible to the stimulating action of prolactin (4.4 +/- 0.68 nmoles/10(8) cells/hour in the presence of 50 ng of prolactin/ml)."}
{"id": "PMID:221280", "title": "Somatostatin: lack of effect of cyclic AMP release and amino acid transport in isolated rat hepatocytes.", "content": "The aim of the present study was to determine whether or not somatostatin can directly affect amino acid transport and cyclic AMP (cAMP) release in isolated rat hepatocytes. Somatostatin at 1.5 microgram/ml (1mumol/l) had no effect on basal uptake of alpha-aminoisobutyric acid (AIB). Similarly, the peptide was without effect on basal cAMP release. Somatostatin exerted a slight but statistically not significant inhibitory effect on glucagon-stimulated AIB uptake and cAMP release. These observations do not support the possibility that somatostatin might directly interfere with hepatic glucose metabolism by altering the entry of amino acids into the liver and--or--by affecting the level of endogenous cAMP.", "contents": "Somatostatin: lack of effect of cyclic AMP release and amino acid transport in isolated rat hepatocytes. The aim of the present study was to determine whether or not somatostatin can directly affect amino acid transport and cyclic AMP (cAMP) release in isolated rat hepatocytes. Somatostatin at 1.5 microgram/ml (1mumol/l) had no effect on basal uptake of alpha-aminoisobutyric acid (AIB). Similarly, the peptide was without effect on basal cAMP release. Somatostatin exerted a slight but statistically not significant inhibitory effect on glucagon-stimulated AIB uptake and cAMP release. These observations do not support the possibility that somatostatin might directly interfere with hepatic glucose metabolism by altering the entry of amino acids into the liver and--or--by affecting the level of endogenous cAMP."}
{"id": "PMID:221281", "title": "Effect of somatostatin on the potentiating action of glucagon, cyclic adenosine monophosphate and theophylline on glucose-induced insulin release.", "content": "The effect of glucagon on the inhibition of the insulin response to glucose induced by somatostatin was investigated in humans and in the isolated perfused rat pancreas. Both in vivo and in vitro somatostatin suppressed glucose-induced insulin release. This inhibitory effect of somatostatin was overcome by glucagon. Similar results have been observed in vitro by the infusion of theophylline or cyclic adenosine monophosphate.", "contents": "Effect of somatostatin on the potentiating action of glucagon, cyclic adenosine monophosphate and theophylline on glucose-induced insulin release. The effect of glucagon on the inhibition of the insulin response to glucose induced by somatostatin was investigated in humans and in the isolated perfused rat pancreas. Both in vivo and in vitro somatostatin suppressed glucose-induced insulin release. This inhibitory effect of somatostatin was overcome by glucagon. Similar results have been observed in vitro by the infusion of theophylline or cyclic adenosine monophosphate."}
{"id": "PMID:221282", "title": "Analysis of the progress of hormone-receptor amplification during differentiation in regenerating planarians.", "content": "Planarians developing from isolated regenerates, when pretreated with epinephrine at different periods of their second regeneration, show a higher rate of sugar uptake than the controls, which were not treated with epinephrine. The hormone receptor development can be influenced most effectively by pretreatments performed during the 1--3 and 6--9 day periods, though some effect can be evoked at any time in the course of the second regeneration. The head regenerates developing from the anterior end of the original midpiece (and regenerating tails the second time, B1) were found to be most sensitive, while the similar regenerates developing from the hindpiece of the original planarian (C) showed the weakest reactivity. The experiments provide further evidence that the hormone receptors' activity can be amplified in the course of regenerative development, leading thus--at a later stage--to a more intense sugar uptake response of the cells.", "contents": "Analysis of the progress of hormone-receptor amplification during differentiation in regenerating planarians. Planarians developing from isolated regenerates, when pretreated with epinephrine at different periods of their second regeneration, show a higher rate of sugar uptake than the controls, which were not treated with epinephrine. The hormone receptor development can be influenced most effectively by pretreatments performed during the 1--3 and 6--9 day periods, though some effect can be evoked at any time in the course of the second regeneration. The head regenerates developing from the anterior end of the original midpiece (and regenerating tails the second time, B1) were found to be most sensitive, while the similar regenerates developing from the hindpiece of the original planarian (C) showed the weakest reactivity. The experiments provide further evidence that the hormone receptors' activity can be amplified in the course of regenerative development, leading thus--at a later stage--to a more intense sugar uptake response of the cells."}
{"id": "PMID:221284", "title": "Titration of total binding sites for growth hormone in rabbit liver. Quantitative modifications of these sites during pregnancy.", "content": "The present work outlines various kinetic parameters of the interaction between bGH (bovine growth hormone) and a receptor located on the membranes of rabbit liver. A dissociation procedure, which strips the hormone off its receptor has been worked out, by varying MgCl2 concentrations and times of contact; exposure to 4 M MgCl2 for 15--30 min was found optimal for dissociation, without denaturing the receptor, as shown by the possibility of rebinding the hormone to the desaturated membranes. This method has been applied to titrate growth hormone receptors in rabbit liver, during pregnancy and lactation. The first half of pregnancy is characterized by a gradual increase of receptor levels and low saturation by endogenous hormone; conversely at parturition, there occurs a striking increase in receptors, which, however, may be demonstrated only after desaturation. During the lactational period, the receptors reamin in part saturated. The results suggest that growth hormone levels increase at parturition and during lactation in the rabbit and hence may play an important role during lactation. The factors which modulate receptor levels at the same period remain unknown.", "contents": "Titration of total binding sites for growth hormone in rabbit liver. Quantitative modifications of these sites during pregnancy. The present work outlines various kinetic parameters of the interaction between bGH (bovine growth hormone) and a receptor located on the membranes of rabbit liver. A dissociation procedure, which strips the hormone off its receptor has been worked out, by varying MgCl2 concentrations and times of contact; exposure to 4 M MgCl2 for 15--30 min was found optimal for dissociation, without denaturing the receptor, as shown by the possibility of rebinding the hormone to the desaturated membranes. This method has been applied to titrate growth hormone receptors in rabbit liver, during pregnancy and lactation. The first half of pregnancy is characterized by a gradual increase of receptor levels and low saturation by endogenous hormone; conversely at parturition, there occurs a striking increase in receptors, which, however, may be demonstrated only after desaturation. During the lactational period, the receptors reamin in part saturated. The results suggest that growth hormone levels increase at parturition and during lactation in the rabbit and hence may play an important role during lactation. The factors which modulate receptor levels at the same period remain unknown."}
{"id": "PMID:221285", "title": "Specific binding of prostaglandin F2 alpha to membranes of rat corpora lutea.", "content": "Prostaglandin F2 alpha (PGF2 alpha) binds specifically to a partially purified membrane preparation from rat corpora lutea. The high affinity, low capacity binding component asa a Kd = 4.7 nM and has a capacity of 0.38 pmol/mg protein. Binding kinetics were temperature-dependent with an association rate constant of 2.5 x 10(5) 1/mol-sec and a dissociation rate constant of 4.3 x 10(-4) sec-1 at 22 degrees C. Little competition for binding was shown by other prostaglandins and prostaglandin metabolites; the PGF2 alpha analogue ICI 81008 (16-m-trifluoromethylphenyl-prostaglandin F2 alpha) showed a binding affinity similar to that of PGF2 alpha. The specific binding of PGF2 alpha to luteal cell membranes was confirmed by electron microscopy using a ferritin--PGF2 alpha conjugate. Ferritin--PGF2 alpha was found predominantly on luteal cell surfaces; little binding occurred on other types of cells present. These data demonstrate specific binding of PGF2 alha to rat luteal membranes. It is suggested that the luteolytic action of PGF2 alpha in the rat may be receptor-mediated.", "contents": "Specific binding of prostaglandin F2 alpha to membranes of rat corpora lutea. Prostaglandin F2 alpha (PGF2 alpha) binds specifically to a partially purified membrane preparation from rat corpora lutea. The high affinity, low capacity binding component asa a Kd = 4.7 nM and has a capacity of 0.38 pmol/mg protein. Binding kinetics were temperature-dependent with an association rate constant of 2.5 x 10(5) 1/mol-sec and a dissociation rate constant of 4.3 x 10(-4) sec-1 at 22 degrees C. Little competition for binding was shown by other prostaglandins and prostaglandin metabolites; the PGF2 alpha analogue ICI 81008 (16-m-trifluoromethylphenyl-prostaglandin F2 alpha) showed a binding affinity similar to that of PGF2 alpha. The specific binding of PGF2 alpha to luteal cell membranes was confirmed by electron microscopy using a ferritin--PGF2 alpha conjugate. Ferritin--PGF2 alpha was found predominantly on luteal cell surfaces; little binding occurred on other types of cells present. These data demonstrate specific binding of PGF2 alha to rat luteal membranes. It is suggested that the luteolytic action of PGF2 alpha in the rat may be receptor-mediated."}
{"id": "PMID:221286", "title": "Down-regulation of testicular androgen biosynthesis and LH receptor levels by an LHRH agonist: role of prolactin.", "content": "Inhibition of plasma prolactin levels by 2-bromo-alpha-ergocryptine (CB-154) caused a 60% decrease and potentiated the inhibitory effects of [D-Ala6,des-Gly-NH2(10)]LHRH ethylamide on testicular LH receptor levels. Animals treated with the LHRH agonist showed reduced plasma and testicular testosterone levels and elevated progesterone concentration. This progesterone rise was further increased in animals having high circulating prolactin levels but was  prevented by CB-154. These data demonstrate that: (1) treatment with the LHRH agonist induces a blockage in the steroidogenic pathway at a step between progesterone and testosterone and (2) prolactin levels to an apparent accentuation of this blockage reflected by higher progesterone levels.", "contents": "Down-regulation of testicular androgen biosynthesis and LH receptor levels by an LHRH agonist: role of prolactin. Inhibition of plasma prolactin levels by 2-bromo-alpha-ergocryptine (CB-154) caused a 60% decrease and potentiated the inhibitory effects of [D-Ala6,des-Gly-NH2(10)]LHRH ethylamide on testicular LH receptor levels. Animals treated with the LHRH agonist showed reduced plasma and testicular testosterone levels and elevated progesterone concentration. This progesterone rise was further increased in animals having high circulating prolactin levels but was  prevented by CB-154. These data demonstrate that: (1) treatment with the LHRH agonist induces a blockage in the steroidogenic pathway at a step between progesterone and testosterone and (2) prolactin levels to an apparent accentuation of this blockage reflected by higher progesterone levels."}
{"id": "PMID:221290", "title": "Suppression of follicular cAMP and steroid response to gonadotrophins by pretreatment with gonadotrophin.", "content": "This study examines the effect of preincubation of sheep ovarian follicles with hCG or FSH on the ability of isolated theca and granulosa to increase cAMP levels in response to a second incubation with hCG or FSH. Secondly, the effect of preincubation of small follicles with hCG on androstenedione and testosterone production is examined in intact follicles. Preincubation with hCG resulted in a decrease in the ability of theca from large (4--6 mm in diameter) and small (1--3 mm) follicles and granulosa from large follicles to increase cAMP levels in response to a second exposure to hCG. Similarly, preincubation with FSH suppressed the response of isolated granulosa from small and large follicles to a second exposure to FSH. A partial, but significant inhibition of the response to the other hormone was observed after preincubation with both FSH and hCG. Intact small follicles pretreated with hCG were unable to increase testosterone secretion in response to a second exposure to hCG.", "contents": "Suppression of follicular cAMP and steroid response to gonadotrophins by pretreatment with gonadotrophin. This study examines the effect of preincubation of sheep ovarian follicles with hCG or FSH on the ability of isolated theca and granulosa to increase cAMP levels in response to a second incubation with hCG or FSH. Secondly, the effect of preincubation of small follicles with hCG on androstenedione and testosterone production is examined in intact follicles. Preincubation with hCG resulted in a decrease in the ability of theca from large (4--6 mm in diameter) and small (1--3 mm) follicles and granulosa from large follicles to increase cAMP levels in response to a second exposure to hCG. Similarly, preincubation with FSH suppressed the response of isolated granulosa from small and large follicles to a second exposure to FSH. A partial, but significant inhibition of the response to the other hormone was observed after preincubation with both FSH and hCG. Intact small follicles pretreated with hCG were unable to increase testosterone secretion in response to a second exposure to hCG."}
{"id": "PMID:221291", "title": "Oestrogen-induced increase in uterine cGMP content: a true hormonal action?", "content": "The dependency of the oestrogen-induced increase in uterine cGMP content towards the cytosol-nuclear receptor system was investigated. The following observations were made: (1) With oestradiol-17 beta (E2-17 beta), U11-100A (UA) or CI-628 (CI) the cGMP response elicited in the uterus of immature rats followed a course that was parallel to (yet delayed by about 1 h from it) the known time-course evolution of nuclear occupancy by the complex formed by each compound with the oestrogen-receptor. (2) While a marked (about 2-fold) increase in uterine cGMP content was obtained with 0.1 microgram E2-17 beta, oestradiol-17 alpha (E2-17 alpha) given at the same dose had no effect on uterine cGMP. (3) The 2--3 h response to E2-17 beta (or to UA) could not be obtained in animals that had received a first injection of E2-17 beta, 2 h, or of one of the anti-oestrogens UA or tamoxifen, 20--22 h prior to the test injection of E2-17 beta. Those 3 treatments have in common that, at the time indicated, they create a state of depletion in the uterine cytosolic receptor population. The cGMP response to E2-17 beta was restored 20--22 h following a first injection of E2-17 beta. This time is known, in this case, to correspond to full replenishment of the cytosol-receptor population. In all those tests, the wet weight increase, measured in the same organs, behaves exactly as did the cGMP response. These results support the conclusion that the increase in uterine cGMP after oestrogen administration to the immature rat, represents a true hormonal action which, like other uterotrophic actions of oestrogens, involves binding of the hormone by the cytosol receptor.", "contents": "Oestrogen-induced increase in uterine cGMP content: a true hormonal action? The dependency of the oestrogen-induced increase in uterine cGMP content towards the cytosol-nuclear receptor system was investigated. The following observations were made: (1) With oestradiol-17 beta (E2-17 beta), U11-100A (UA) or CI-628 (CI) the cGMP response elicited in the uterus of immature rats followed a course that was parallel to (yet delayed by about 1 h from it) the known time-course evolution of nuclear occupancy by the complex formed by each compound with the oestrogen-receptor. (2) While a marked (about 2-fold) increase in uterine cGMP content was obtained with 0.1 microgram E2-17 beta, oestradiol-17 alpha (E2-17 alpha) given at the same dose had no effect on uterine cGMP. (3) The 2--3 h response to E2-17 beta (or to UA) could not be obtained in animals that had received a first injection of E2-17 beta, 2 h, or of one of the anti-oestrogens UA or tamoxifen, 20--22 h prior to the test injection of E2-17 beta. Those 3 treatments have in common that, at the time indicated, they create a state of depletion in the uterine cytosolic receptor population. The cGMP response to E2-17 beta was restored 20--22 h following a first injection of E2-17 beta. This time is known, in this case, to correspond to full replenishment of the cytosol-receptor population. In all those tests, the wet weight increase, measured in the same organs, behaves exactly as did the cGMP response. These results support the conclusion that the increase in uterine cGMP after oestrogen administration to the immature rat, represents a true hormonal action which, like other uterotrophic actions of oestrogens, involves binding of the hormone by the cytosol receptor."}
{"id": "PMID:221296", "title": "Use of reflected green light for specific identification of islets in vitro after collagenase isolation.", "content": "A simple technique is described that permits specific identification in vitro of isolated islets as contrasted with samll lymph nodes.", "contents": "Use of reflected green light for specific identification of islets in vitro after collagenase isolation. A simple technique is described that permits specific identification in vitro of isolated islets as contrasted with samll lymph nodes."}
{"id": "PMID:221297", "title": "High concentration of gamma-aminobutyric acid in pancreatic beta cells.", "content": "The gamma-aminobutyric acid (GABA) concentration of pancreatic islets in rats treated with streptozotocin (STZ) and of human insulinoma tissue was studied. Seven hours after the administration of 65 mg/kg body weight of STZ, a distinct increase in serum insulin concentration and at the same time a decrease in blood glucose level were seen. Twenty-four hours after the injection of STZ, however, the level of serum insulin decreased much, whereas that of blood glucose increased considerably. On the other hand, the GABA concentration of the islet was reduced dramatically to about one-tenth the control level after both 7 and 24 h. The histologic investigations of the islets revealed the destruction of B cells but no changes in A and D cells 7 and 24 h after the treatment of STZ. Nerve fibers and nerve endings in the islets were preserved intact all through the study. The GABA and insulin contents of the two cases of human insulinoma were determined. One insulinoma, which was compactly occupied with B cells according to its histologic features, contained a high concentration of GABA. The other tumor, having a rather sparse distribution of B cells in it as compared with the former case, possessed a lower concentration of GABA, but it was still high compared with that of its surrounding tissues. The present observations indicate that a large amount of GABA is available in the B cells of the pancreatic islets.", "contents": "High concentration of gamma-aminobutyric acid in pancreatic beta cells. The gamma-aminobutyric acid (GABA) concentration of pancreatic islets in rats treated with streptozotocin (STZ) and of human insulinoma tissue was studied. Seven hours after the administration of 65 mg/kg body weight of STZ, a distinct increase in serum insulin concentration and at the same time a decrease in blood glucose level were seen. Twenty-four hours after the injection of STZ, however, the level of serum insulin decreased much, whereas that of blood glucose increased considerably. On the other hand, the GABA concentration of the islet was reduced dramatically to about one-tenth the control level after both 7 and 24 h. The histologic investigations of the islets revealed the destruction of B cells but no changes in A and D cells 7 and 24 h after the treatment of STZ. Nerve fibers and nerve endings in the islets were preserved intact all through the study. The GABA and insulin contents of the two cases of human insulinoma were determined. One insulinoma, which was compactly occupied with B cells according to its histologic features, contained a high concentration of GABA. The other tumor, having a rather sparse distribution of B cells in it as compared with the former case, possessed a lower concentration of GABA, but it was still high compared with that of its surrounding tissues. The present observations indicate that a large amount of GABA is available in the B cells of the pancreatic islets."}
{"id": "PMID:221298", "title": "Hepatic effects of chlorpropamide: inhibition of glucagon-stimulated gluconeogenesis in perfused livers of fasted rats.", "content": "In perfused livers of rats fasted for 24 h, glucagon (5 x 10(-10) M) significantly elevated tissue and perfusate levels of cyclic AMP and caused a twofold increase in glucose formation from lactate. Chlorpropamide (0.8 x 10(-3) M) consistently blocked these effects. Measurements of metabolic intermediates suggest that chlorpropamide may inhibit gluconeogenesis by antagonizing the action of glucagon on the phosphoenolpyruvate cycle. In the experiments described, chlorpropamide did not lower hepatic ATP concentration or energy charge, and exerted its effects at perfusate concentrations comparable to serum concentrations reported in patients on maintenance doses of the drug.", "contents": "Hepatic effects of chlorpropamide: inhibition of glucagon-stimulated gluconeogenesis in perfused livers of fasted rats. In perfused livers of rats fasted for 24 h, glucagon (5 x 10(-10) M) significantly elevated tissue and perfusate levels of cyclic AMP and caused a twofold increase in glucose formation from lactate. Chlorpropamide (0.8 x 10(-3) M) consistently blocked these effects. Measurements of metabolic intermediates suggest that chlorpropamide may inhibit gluconeogenesis by antagonizing the action of glucagon on the phosphoenolpyruvate cycle. In the experiments described, chlorpropamide did not lower hepatic ATP concentration or energy charge, and exerted its effects at perfusate concentrations comparable to serum concentrations reported in patients on maintenance doses of the drug."}
{"id": "PMID:221299", "title": "Hepatic glucose-6-phosphatase activities and correlated ultrastructural alterations in hepatocytes of diabetic rats.", "content": "Cell fractionation, enzyme analysis, and electron microscopy were used to study the effects of streptozotocin-induced diabetes and insulin replacement on liver structure and function. In liver homogenates from diabetic rats, glucose-6-phosphatase (G-6-Pase) activity was stimulated about 2 1/2-fold over that found in normal animals. Analyses of isolated rough and smooth microsomes from diabetic rats for G-6-Pase activity showed a fourfold increase in the smooth microsomes and a small increase in enzyme activity in rough microsomes when compared with these fractions from control animals. Associated with the increased enzyme activity was a reduction in liver glycogen. Insulin treatment of the diabetic rats caused a fall in homogenate G-6-Pase levels to approximately normal values and stimulated the accumulation of hepatic glycogen. Administration of insulin to these animals also caused a decrease in G-6-Pase activity, which was most pronounced in the smooth microsomes. Studies with the electron microscope revealed ultrastructural alterations in livers of the diabetic rats, which were most striking in the periportal region of the lobule. Periportal hepatocytes from diabetic rats displayed dispersed particles of glycogen separated by cytoplasm rich in SER rather than dense masses of glycogen with little SER, as is characteristic of these cells in normal animals. Centrilobular cells from the diabetic animals displayed some disorganization of the RER and a dispersed pattern of glycogen with abundant SER, similar to the pattern found in these cells from normal animals. After insulin treatment the periportal cells appeared normal morphologically, whereas the centrilobular hepatocytes displayed regions of both dense masses and dispersed glycogen. In the glycogen masses, little SER was found; however, in the areas of dispersed glycogen particles, an abundance of this organelle was evident. We conclude from these studies that diabetes causes an increase in amount of hepatic smooth endoplasmic reticulum (SER), especially within periportal hepatocytes. The results of cell fractionation indicate that membranes of the smooth endoplasmic reticulum are enriched in G-6-pase. We interpret these results to indicate that diabetes causes hepatocytes to form additional smooth endoplasmic reticulum with specialized membranes, at least with respect to G-6-Pase. It is suggested that this cellular specialization is a response of the hepatocyte to the diabetic state, namely, a demand for increased hepatic glucose production and release into the blood stream, thus contributing to the hyperglycemia characteristic of this disease. Insulin administration to the diabetic animals reverses the above alterations.", "contents": "Hepatic glucose-6-phosphatase activities and correlated ultrastructural alterations in hepatocytes of diabetic rats. Cell fractionation, enzyme analysis, and electron microscopy were used to study the effects of streptozotocin-induced diabetes and insulin replacement on liver structure and function. In liver homogenates from diabetic rats, glucose-6-phosphatase (G-6-Pase) activity was stimulated about 2 1/2-fold over that found in normal animals. Analyses of isolated rough and smooth microsomes from diabetic rats for G-6-Pase activity showed a fourfold increase in the smooth microsomes and a small increase in enzyme activity in rough microsomes when compared with these fractions from control animals. Associated with the increased enzyme activity was a reduction in liver glycogen. Insulin treatment of the diabetic rats caused a fall in homogenate G-6-Pase levels to approximately normal values and stimulated the accumulation of hepatic glycogen. Administration of insulin to these animals also caused a decrease in G-6-Pase activity, which was most pronounced in the smooth microsomes. Studies with the electron microscope revealed ultrastructural alterations in livers of the diabetic rats, which were most striking in the periportal region of the lobule. Periportal hepatocytes from diabetic rats displayed dispersed particles of glycogen separated by cytoplasm rich in SER rather than dense masses of glycogen with little SER, as is characteristic of these cells in normal animals. Centrilobular cells from the diabetic animals displayed some disorganization of the RER and a dispersed pattern of glycogen with abundant SER, similar to the pattern found in these cells from normal animals. After insulin treatment the periportal cells appeared normal morphologically, whereas the centrilobular hepatocytes displayed regions of both dense masses and dispersed glycogen. In the glycogen masses, little SER was found; however, in the areas of dispersed glycogen particles, an abundance of this organelle was evident. We conclude from these studies that diabetes causes an increase in amount of hepatic smooth endoplasmic reticulum (SER), especially within periportal hepatocytes. The results of cell fractionation indicate that membranes of the smooth endoplasmic reticulum are enriched in G-6-pase. We interpret these results to indicate that diabetes causes hepatocytes to form additional smooth endoplasmic reticulum with specialized membranes, at least with respect to G-6-Pase. It is suggested that this cellular specialization is a response of the hepatocyte to the diabetic state, namely, a demand for increased hepatic glucose production and release into the blood stream, thus contributing to the hyperglycemia characteristic of this disease. Insulin administration to the diabetic animals reverses the above alterations."}
{"id": "PMID:221300", "title": "Heterotransplantation of human stomach carcinoma in nude mice.", "content": "Thirty-five primary tumors and 14 metastatic lymph nodes from stomach cancer patients were transplanted in nude mice. Successful transplantation was obtained in 16 cases of primary tumors and 5 cases of metastatic lymph nodes. The tumors growing in the nude mouse displayed histological features similar to those of the original human tumors. Eight cases of the successful takes have been maintained by consecutive transplantation. Nine cases have been stored in liquid nitrogen. The transplanted tumors were observed to spread to the distant lymph nodes in 3 cases out of the 17 successive transplants.", "contents": "Heterotransplantation of human stomach carcinoma in nude mice. Thirty-five primary tumors and 14 metastatic lymph nodes from stomach cancer patients were transplanted in nude mice. Successful transplantation was obtained in 16 cases of primary tumors and 5 cases of metastatic lymph nodes. The tumors growing in the nude mouse displayed histological features similar to those of the original human tumors. Eight cases of the successful takes have been maintained by consecutive transplantation. Nine cases have been stored in liquid nitrogen. The transplanted tumors were observed to spread to the distant lymph nodes in 3 cases out of the 17 successive transplants."}
{"id": "PMID:221302", "title": "Immunological cross reaction between sera from patients with breast cancer and mouse mammary tumor virus.", "content": "Sera of Japanese women with breast cancer and without disorders of the mammary gland gave positive immunofluorescence reaction with mouse mammary tumor cells (MMT cells) producing type-A and type-B virus particles. Among these, 55.1% (49/89) of the sera from patients with breast cancer reacted with MMT cells, whereas 60% (3/5) of the sera from patients with benign mammary hyperplasia (2 of 3 mastopathies, 1 of 2 cystosarcoma phyllodes), 30% (12/40) of the patients with other than breast cancer (4 of 14 stomach cancers, 6 of 20 uterine cancers, 1 of 3 lung cancers, 1 of 3 rectum cancers), and 26.5% (18/68) of the sera from apparently healthy women showed positive reaction with MMT cells. Distribution pattern of the specific fluorescence obtained with positive human sera was similar to that resulting from the reaction with rabbit antiserum of type-A particles. Results of absorption studies and blocking tests also suggested that the reaction was due to the antigenic components common to type-A and -B particles. Furthermore, the results of membrane immunofluorescence tests suggested that some human sera also react with envelope antigen(s) of B particles. Antinuclear antibody was found in sera from 15.7% (14/89) of breast cancer patients by the indirect immunofluorescence tests, and antibody cross-reacting with mouse mammary tumor virus was not found in most of the sera from breast cancer patients who have antinuclear antibody.", "contents": "Immunological cross reaction between sera from patients with breast cancer and mouse mammary tumor virus. Sera of Japanese women with breast cancer and without disorders of the mammary gland gave positive immunofluorescence reaction with mouse mammary tumor cells (MMT cells) producing type-A and type-B virus particles. Among these, 55.1% (49/89) of the sera from patients with breast cancer reacted with MMT cells, whereas 60% (3/5) of the sera from patients with benign mammary hyperplasia (2 of 3 mastopathies, 1 of 2 cystosarcoma phyllodes), 30% (12/40) of the patients with other than breast cancer (4 of 14 stomach cancers, 6 of 20 uterine cancers, 1 of 3 lung cancers, 1 of 3 rectum cancers), and 26.5% (18/68) of the sera from apparently healthy women showed positive reaction with MMT cells. Distribution pattern of the specific fluorescence obtained with positive human sera was similar to that resulting from the reaction with rabbit antiserum of type-A particles. Results of absorption studies and blocking tests also suggested that the reaction was due to the antigenic components common to type-A and -B particles. Furthermore, the results of membrane immunofluorescence tests suggested that some human sera also react with envelope antigen(s) of B particles. Antinuclear antibody was found in sera from 15.7% (14/89) of breast cancer patients by the indirect immunofluorescence tests, and antibody cross-reacting with mouse mammary tumor virus was not found in most of the sera from breast cancer patients who have antinuclear antibody."}
{"id": "PMID:221303", "title": "Clinical studies on carcinoembryonic antigen in pancreatic cancer.", "content": "We studied serum carcinoembryonic antigen (CEA) levels in 82 patients. Thirty-four of these had benign diseases while 48 had malignant diseases. Highest incidence and levels of CEA occurred in the sera of patients with pancreatic cancer and stomach cancer. In this paper we focused our particular attention on the serum CEA of 25 pancreatic cancer patients, and examined differences in serum CEA levels in relation to histologic differentiation and sites of pancreatric cancer. No statistical difference in serum CEA level was found among various histologic types and sites of the pancreatic cancer. Clinical courses of two patients with pancreatic cancer were also studied. Serial determinations of CEA levels are most useful in assessing the effect of operation or chemotherapies and are a useful indicator for differentiating pancreatic cancer from chronic pancreatitis but cannot be a conclusive factor for the diagnosis. Finally, we correlated serum CEA levels with those of RNase and confirmed a positive correlation.", "contents": "Clinical studies on carcinoembryonic antigen in pancreatic cancer. We studied serum carcinoembryonic antigen (CEA) levels in 82 patients. Thirty-four of these had benign diseases while 48 had malignant diseases. Highest incidence and levels of CEA occurred in the sera of patients with pancreatic cancer and stomach cancer. In this paper we focused our particular attention on the serum CEA of 25 pancreatic cancer patients, and examined differences in serum CEA levels in relation to histologic differentiation and sites of pancreatric cancer. No statistical difference in serum CEA level was found among various histologic types and sites of the pancreatic cancer. Clinical courses of two patients with pancreatic cancer were also studied. Serial determinations of CEA levels are most useful in assessing the effect of operation or chemotherapies and are a useful indicator for differentiating pancreatic cancer from chronic pancreatitis but cannot be a conclusive factor for the diagnosis. Finally, we correlated serum CEA levels with those of RNase and confirmed a positive correlation."}
{"id": "PMID:221305", "title": "Well-differentiated peripheral cholangiocarcinoma with an unusual clinical course.", "content": "A patient with an unresectable well-differentiated bile duct tumor who survived for 15 yr after biopsy diagnosis is presented. Histologic examination of the tumor revealed bland features of bile duct adenoma despite extensive spread within the liver. Over its subsequent course, the tumor progressively replaced the liver, achieving huge size, although there was no evidence of metastases until shortly before the patient's death. This clinical course was very unusual for either bile duct adenoma or cholangiocarcinoma, but would be more characteristic of another tumor of intrahepatic bile duct origin, the biliary cystadenoma. However, this latter diagnosis was excluded with both gross and microscopic pathologic criteria. Evidence is presented to support classification of this tumor as an unusual varient of peripheral cholangiocarcinoma which requires correlation of the clinical and pathologic findings for correst diagnosis.", "contents": "Well-differentiated peripheral cholangiocarcinoma with an unusual clinical course. A patient with an unresectable well-differentiated bile duct tumor who survived for 15 yr after biopsy diagnosis is presented. Histologic examination of the tumor revealed bland features of bile duct adenoma despite extensive spread within the liver. Over its subsequent course, the tumor progressively replaced the liver, achieving huge size, although there was no evidence of metastases until shortly before the patient's death. This clinical course was very unusual for either bile duct adenoma or cholangiocarcinoma, but would be more characteristic of another tumor of intrahepatic bile duct origin, the biliary cystadenoma. However, this latter diagnosis was excluded with both gross and microscopic pathologic criteria. Evidence is presented to support classification of this tumor as an unusual varient of peripheral cholangiocarcinoma which requires correlation of the clinical and pathologic findings for correst diagnosis."}
{"id": "PMID:221308", "title": "RNA synthesis of vesicular stomatitis virus. VIII. Oligonucleotides of the structural genes and mRNA.", "content": "The single-stranded RNA genome of vesicular stomatitis virus (VSV, Indiana serotype, San Juan strain) yields approx. 75 RNase T1-resistant oligonucleotides ranging in size from 10 to 50 bases. Each of the five structural genes, isolated as duplex RNA molecules hybridized to complementary mRNA, contains two or more of these large oligonucleotides. One of the oligonucleotides is identified as part of the non-coding region near the 3' end of the genome. Comparison of these results with others indicate that the RNA sequence of VSV is apparently stable in the laboratory but not in the wild. RNase T1-resistant oligonucleotides are also shown for all five VSV mRN species. Whether the mRNA for these digestions are are isolated from duplex RNA molecules or as single-stranded RNA species, the oligonucleotide patterns for each mRNA are virtually identical, indicating that each mRNA is transcribed from contiguous sequences on the genome. Comparison with published oligonucleotide patterns obtained from other isolates of VSV or from VSV deletion mutants indicate that identity and changes in their genome structure can be correlated with specific structural genes.", "contents": "RNA synthesis of vesicular stomatitis virus. VIII. Oligonucleotides of the structural genes and mRNA. The single-stranded RNA genome of vesicular stomatitis virus (VSV, Indiana serotype, San Juan strain) yields approx. 75 RNase T1-resistant oligonucleotides ranging in size from 10 to 50 bases. Each of the five structural genes, isolated as duplex RNA molecules hybridized to complementary mRNA, contains two or more of these large oligonucleotides. One of the oligonucleotides is identified as part of the non-coding region near the 3' end of the genome. Comparison of these results with others indicate that the RNA sequence of VSV is apparently stable in the laboratory but not in the wild. RNase T1-resistant oligonucleotides are also shown for all five VSV mRN species. Whether the mRNA for these digestions are are isolated from duplex RNA molecules or as single-stranded RNA species, the oligonucleotide patterns for each mRNA are virtually identical, indicating that each mRNA is transcribed from contiguous sequences on the genome. Comparison with published oligonucleotide patterns obtained from other isolates of VSV or from VSV deletion mutants indicate that identity and changes in their genome structure can be correlated with specific structural genes."}
{"id": "PMID:221310", "title": "Decrease in serum receptor-reactive somatomedin in diabetes.", "content": "Somatomedin in rat serum has been measured by a sensitive radioreceptor assay using 125I-labelled human somatomedin and human placental membrane. In rats made diabetic with strepotzotocin, receptor-reactive somatomedin levels were decrease by up to 75%. The decrease followed the time course of increasing serum glucose and occurred to the same extent in rats aged between 4 and 40 weeks. Endogenous serum receptor-reactive somatomedin appeared exclusively in high molecular weight fractions on gel chromatography. In diabetes the decreased somatomedin was due to a fall in this high molecular weight activity, but was not accompanied by a fall in somatomedin binding protein. These results suggest a role for insulin in maintaining serum somatomedin levels.", "contents": "Decrease in serum receptor-reactive somatomedin in diabetes. Somatomedin in rat serum has been measured by a sensitive radioreceptor assay using 125I-labelled human somatomedin and human placental membrane. In rats made diabetic with strepotzotocin, receptor-reactive somatomedin levels were decrease by up to 75%. The decrease followed the time course of increasing serum glucose and occurred to the same extent in rats aged between 4 and 40 weeks. Endogenous serum receptor-reactive somatomedin appeared exclusively in high molecular weight fractions on gel chromatography. In diabetes the decreased somatomedin was due to a fall in this high molecular weight activity, but was not accompanied by a fall in somatomedin binding protein. These results suggest a role for insulin in maintaining serum somatomedin levels."}
{"id": "PMID:221311", "title": "Normal fluctuations in the concentration of corticosteroid and adrenocorticotrophin in the plasma of foetal and pregnant sheep.", "content": "Changes in the concentration of adrenocorticotrophin and corticosteroid in the plasma of pregnant and foetal sheep have been followed at different times of day. Wide fluctuations were seen in the concentrations of both in the foetus and ewe, although no evidence for a diurnal rhythm in the ewe was obtained. The foetal plasma adrenocorticotrophin was higher at 07.00-11.00 h than at 21.00-01.00 h, but no corticosteroid rhythm was observed. A consistently close relationship between maternal and foetal hormone concentrations was not observed. The diurnal rhythm in adrenocorticotrophin concentration in the foetus is discussed in relation to rhythms in indicators of central nervous activity.", "contents": "Normal fluctuations in the concentration of corticosteroid and adrenocorticotrophin in the plasma of foetal and pregnant sheep. Changes in the concentration of adrenocorticotrophin and corticosteroid in the plasma of pregnant and foetal sheep have been followed at different times of day. Wide fluctuations were seen in the concentrations of both in the foetus and ewe, although no evidence for a diurnal rhythm in the ewe was obtained. The foetal plasma adrenocorticotrophin was higher at 07.00-11.00 h than at 21.00-01.00 h, but no corticosteroid rhythm was observed. A consistently close relationship between maternal and foetal hormone concentrations was not observed. The diurnal rhythm in adrenocorticotrophin concentration in the foetus is discussed in relation to rhythms in indicators of central nervous activity."}
{"id": "PMID:221312", "title": "Direct effects of trypan blue on thyroid secretion.", "content": "Trypan blue directly inhibited in vitro thyroid secretion (butanol soluble 125I release to the media) induced by both thyroid stimulating hormone (TSH) and dibutyryl cAMP. Intracellular colloid droplet counts were also decreased. Inhibition was directly proportional to dye concentration and could be overcome by supramaximal TSH and dibutyryl cAMP. Inhibition could be observed as early as 20 min of incubation, was not increased by preincubation, and could even be demonstrated after TSH in vivo. Trypan blue, in vivo, produced similar inhibition of thyroid secretion. Incubation of 125I-thyroglobulin with lysosomal enzymes revealed inhibition with much lower concentrations of dye. Inhibition of lysosomal enzyme(s) would not appear to explain the marked decreases in colloid droplets, and this may represent two separate effects of trypan blue on thyroid secretion.", "contents": "Direct effects of trypan blue on thyroid secretion. Trypan blue directly inhibited in vitro thyroid secretion (butanol soluble 125I release to the media) induced by both thyroid stimulating hormone (TSH) and dibutyryl cAMP. Intracellular colloid droplet counts were also decreased. Inhibition was directly proportional to dye concentration and could be overcome by supramaximal TSH and dibutyryl cAMP. Inhibition could be observed as early as 20 min of incubation, was not increased by preincubation, and could even be demonstrated after TSH in vivo. Trypan blue, in vivo, produced similar inhibition of thyroid secretion. Incubation of 125I-thyroglobulin with lysosomal enzymes revealed inhibition with much lower concentrations of dye. Inhibition of lysosomal enzyme(s) would not appear to explain the marked decreases in colloid droplets, and this may represent two separate effects of trypan blue on thyroid secretion."}
{"id": "PMID:221314", "title": "Predicting patient outcome: the contribution of prehospital, inhospital, and posthospital factors.", "content": "Data on variables often used in recidivism studies were gathered from state hospital records of 129 patients released within a two-year period to a three-county area in West Virginia. The variables were categorized as prehospital, inhospital, or posthospital; the relationship between each variable set and recidivism was determined. The three criteria of recidivism were readmission within one year following discharge, number of days in the community, and number of days to first readmission. Inhospital variables were found to be the best predictors for all three outcome measures. When the number of variables in the set was controlled for, the posthospital set and the inhospital set had the same predictive power for readmission within one year of discharge and number of days to readmission. Posthospital variables were poorest at predicitng, among recidivism criteria, the number of days in the community.", "contents": "Predicting patient outcome: the contribution of prehospital, inhospital, and posthospital factors. Data on variables often used in recidivism studies were gathered from state hospital records of 129 patients released within a two-year period to a three-county area in West Virginia. The variables were categorized as prehospital, inhospital, or posthospital; the relationship between each variable set and recidivism was determined. The three criteria of recidivism were readmission within one year following discharge, number of days in the community, and number of days to first readmission. Inhospital variables were found to be the best predictors for all three outcome measures. When the number of variables in the set was controlled for, the posthospital set and the inhospital set had the same predictive power for readmission within one year of discharge and number of days to readmission. Posthospital variables were poorest at predicitng, among recidivism criteria, the number of days in the community."}
{"id": "PMID:221315", "title": "Viral vaccines: new problems and prospects.", "content": "The problems are many: how best to apply the swine flu lessons to the Russian flu \"invasion;\" whether enough is known about the cytomegalovirus to attempt vaccine development; how to deliver established vaccines to the millions who need them.", "contents": "Viral vaccines: new problems and prospects. The problems are many: how best to apply the swine flu lessons to the Russian flu \"invasion;\" whether enough is known about the cytomegalovirus to attempt vaccine development; how to deliver established vaccines to the millions who need them."}
{"id": "PMID:221316", "title": "The viral hepatitides.", "content": "Vaccines and chemotherapy may soon strengthen the armamentarium for control of type B hepatitis. The incidence of type A is still declining in the U.S., and now that type non-A, non-B has been transmitted to animals, a marker for it is being widely sought.", "contents": "The viral hepatitides. Vaccines and chemotherapy may soon strengthen the armamentarium for control of type B hepatitis. The incidence of type A is still declining in the U.S., and now that type non-A, non-B has been transmitted to animals, a marker for it is being widely sought."}
{"id": "PMID:221317", "title": "Cushing's syndrome: a tripartite entity.", "content": "The three distinct etiologies of Cushing's syndrome usually reflect the presence of a neoplasm, most often but not necessarily of the pituitary, and all ultimately result in hypercortisolism. Recent advances in diagnosis and treatment have vastly improved the outlook for many patients. Several therapeutic options are outlined, the success of which depends on accurate identification of the cause of hypercortisolism.", "contents": "Cushing's syndrome: a tripartite entity. The three distinct etiologies of Cushing's syndrome usually reflect the presence of a neoplasm, most often but not necessarily of the pituitary, and all ultimately result in hypercortisolism. Recent advances in diagnosis and treatment have vastly improved the outlook for many patients. Several therapeutic options are outlined, the success of which depends on accurate identification of the cause of hypercortisolism."}
{"id": "PMID:221318", "title": "Metabolic requirements for renal function.", "content": "Renal mass accounts for only 0.5% of body weight, yet the kidney consumes 7% of the body's total oxygen uptake. Most is used for tubular transport, but a significant portion contributes to less well-recognized aspects of renal function. Cortical gluconeogenesis capacity, for example, exceeds that of the liver per gram of tissue. Basal and transport metabolic processes are examined in terms of clinical relevance.", "contents": "Metabolic requirements for renal function. Renal mass accounts for only 0.5% of body weight, yet the kidney consumes 7% of the body's total oxygen uptake. Most is used for tubular transport, but a significant portion contributes to less well-recognized aspects of renal function. Cortical gluconeogenesis capacity, for example, exceeds that of the liver per gram of tissue. Basal and transport metabolic processes are examined in terms of clinical relevance."}
{"id": "PMID:221321", "title": "Structural organization of human cytomegalovirus DNA.", "content": "HCMV DNA preparations in which purity was characterized by sedimentation, buoyant density, and restriction enzyme cleavage contain two molecular weight size classes of HCMV DNA molecules (150--155 x 10(6) and 100 x 10(6) daltons) in addition to some shear products. Partial denaturation mapping reveals that both size classes contain the same sequences and that molecules of 150--155 x 10(6) daltons contain the apparent full complement of sequences which are variously contained in the smaller molecules. The complete genome (150--155 x 10(6) daltons) seems to be divisible into regions of about 78--82% and 18--22%, which undergo complete inversions with respect to one another. Enriched or purified preparations of molecules of 150--155 x 10(6) daltons generate cleavage products identical to those from total HCMV DNA preparations.", "contents": "Structural organization of human cytomegalovirus DNA. HCMV DNA preparations in which purity was characterized by sedimentation, buoyant density, and restriction enzyme cleavage contain two molecular weight size classes of HCMV DNA molecules (150--155 x 10(6) and 100 x 10(6) daltons) in addition to some shear products. Partial denaturation mapping reveals that both size classes contain the same sequences and that molecules of 150--155 x 10(6) daltons contain the apparent full complement of sequences which are variously contained in the smaller molecules. The complete genome (150--155 x 10(6) daltons) seems to be divisible into regions of about 78--82% and 18--22%, which undergo complete inversions with respect to one another. Enriched or purified preparations of molecules of 150--155 x 10(6) daltons generate cleavage products identical to those from total HCMV DNA preparations."}
{"id": "PMID:221322", "title": "Physical mapping of herpes simplex virus-coded functions and polypeptides by marker rescue and analysis of HSV-1/HSV-2 intertypic recombinants.", "content": "A number of temperature-sensitive (ts) mutants and one pyrimidine deoxyribonucleoside kinase-deficient mutant of herpes simplex virus (HSV), have been located on the physical map of the genome by means of marker rescue experiments and by the analysis of the crossover points in intertypic recombinants between HSV types 1 and 2. The physical map is compared to the genetic map and certain anomalies identified. Analysis of infected-cell polypeptides specified by intertypic recombinants has allowed tentative map co-ordinates to be assigned to the structural genes (or genes which cause post-translational modification) for many of the polypeptides. Immediate-early, phosphorylated, glycosylated and structural as well as non-structural polypeptides have been analysed in this way and it can be concluded that there is no restriction of any of these groups of polypeptides to either the long or the short regions of the genome. One of the recombinants, 2853, is at least partially \"frozen\" in one orientation of the long region. This orientation is also the one which exhibits a minimum number of crossovers in three other recombinants.", "contents": "Physical mapping of herpes simplex virus-coded functions and polypeptides by marker rescue and analysis of HSV-1/HSV-2 intertypic recombinants. A number of temperature-sensitive (ts) mutants and one pyrimidine deoxyribonucleoside kinase-deficient mutant of herpes simplex virus (HSV), have been located on the physical map of the genome by means of marker rescue experiments and by the analysis of the crossover points in intertypic recombinants between HSV types 1 and 2. The physical map is compared to the genetic map and certain anomalies identified. Analysis of infected-cell polypeptides specified by intertypic recombinants has allowed tentative map co-ordinates to be assigned to the structural genes (or genes which cause post-translational modification) for many of the polypeptides. Immediate-early, phosphorylated, glycosylated and structural as well as non-structural polypeptides have been analysed in this way and it can be concluded that there is no restriction of any of these groups of polypeptides to either the long or the short regions of the genome. One of the recombinants, 2853, is at least partially \"frozen\" in one orientation of the long region. This orientation is also the one which exhibits a minimum number of crossovers in three other recombinants."}
{"id": "PMID:221323", "title": "Integration of Epstein-Barr virus DNA.", "content": "The application to herpesviruses of different standard methods fo measuring tumour-virus integration is discussed. The evidence for the presence of integrated virus DNA in EBV-transformed cells is summarized.", "contents": "Integration of Epstein-Barr virus DNA. The application to herpesviruses of different standard methods fo measuring tumour-virus integration is discussed. The evidence for the presence of integrated virus DNA in EBV-transformed cells is summarized."}
{"id": "PMID:221324", "title": "Episomal viral DNA in herpesvirus saimiri-transformed lymphoid cell lines.", "content": "Structural analysis of episomal viral genomes from two herpesvirus saimiri (HVS)-transformed tumour cell lines (No. 1670 and 70N2) showed that both types of episomes have a higher molecular weight than linear virion DNA. The arrangement of unique (L) and repetitive (H) DNA in No. 1670 episomes was studied by partial denaturation mapping. Part of the L-sequences present in linear virion DNA was found to be missing, part was found to be duplicated in the episomes. The episomal L-DNA regions were correlated with the known physical gene maps of linear HVS DNA.", "contents": "Episomal viral DNA in herpesvirus saimiri-transformed lymphoid cell lines. Structural analysis of episomal viral genomes from two herpesvirus saimiri (HVS)-transformed tumour cell lines (No. 1670 and 70N2) showed that both types of episomes have a higher molecular weight than linear virion DNA. The arrangement of unique (L) and repetitive (H) DNA in No. 1670 episomes was studied by partial denaturation mapping. Part of the L-sequences present in linear virion DNA was found to be missing, part was found to be duplicated in the episomes. The episomal L-DNA regions were correlated with the known physical gene maps of linear HVS DNA."}
{"id": "PMID:221325", "title": "Herpesvirus papio: state of viral DNA in baboon lymphoblastoid cell lines.", "content": "Baboon lymphoblastoid cell lines (LCL) transformed with herpesvirus papio were evaluated for the state of HVP DNA in the cells by caesium chloride density-gradient centrifugation and DNA-cRNA filter hybridization. Five HVP producer cultures and one non-producer culture were studied and non-integrated and integrated HVP DNA were detected in all producer cultures whereas only integrated HVP DNA could be demonstrated in the non-producer LCL. Non-integrated HVP dna had a density of 1.715--1.716 g/cm3 in caesium chloride corresponding to a guanine + cytosine content of 56--57%.", "contents": "Herpesvirus papio: state of viral DNA in baboon lymphoblastoid cell lines. Baboon lymphoblastoid cell lines (LCL) transformed with herpesvirus papio were evaluated for the state of HVP DNA in the cells by caesium chloride density-gradient centrifugation and DNA-cRNA filter hybridization. Five HVP producer cultures and one non-producer culture were studied and non-integrated and integrated HVP DNA were detected in all producer cultures whereas only integrated HVP DNA could be demonstrated in the non-producer LCL. Non-integrated HVP dna had a density of 1.715--1.716 g/cm3 in caesium chloride corresponding to a guanine + cytosine content of 56--57%."}
{"id": "PMID:221326", "title": "Annealing of alkali-resistant HSV DNA strands and isolation of S and L components.", "content": "DNA isolated from highly purified virions of herpes simplex virus type-1 (HF strain) was denatured by centrifugation in alkaline sucrose gradients. DNA molecules corresponding to intact single-stranded virion DNA (50 x 10(6) daltons) were isolated and adjusted to neutral pH. The DNA was annealed under conditions permitting reassociation of intact single-stranded molecules and studied by electron microscopy. Three classes of DNA molecules showing double-stranded sequences were observed: (a) fully double-stranded DNA molecules the size of the intact HSV DNA genome, namely 52 micron; (b) DNA hybrids with a region of partial double-strandedness ranging from 5 to 12 micron, plus long single strands; and (c) DNA hybrids with a double-stranded region of 32--40 micron, plus short single strands. (These results suggest that the alkali-resistant single-stranded HSV DNA molecules are composed of several subclasses that permit annealing of either the total genome or the S or L components.) The 5 micron double-stranded region probably constitutes the S component of HSV DNA and the sequences longer than 5 micron and shorter than 12 micron represent annealing of the repeat sequences on either or both sides of the S component. The double-stranded sequences with a length of 32--40 micron may represent the L component. Treatment of the annealed, partially double-stranded hybrid DNA molecules with S1 endonuclease to remove the single-stranded termini and centrifugation in neutral sucrose gradients yielded two distinct peaks. Centrifugation of fractions from the two peaks in caesium chloride density gradients showed that the small DNA component (possibly the S and the repeat sequences) had a higher buoyant density and the longer (possibly the L) DNA component had a lower density than the HSV DNA marker. Annealing of alkali-resistant viral DNA strands therefore provides a means of isolating the L, S and repeat sequence regions of HSV DNA.", "contents": "Annealing of alkali-resistant HSV DNA strands and isolation of S and L components. DNA isolated from highly purified virions of herpes simplex virus type-1 (HF strain) was denatured by centrifugation in alkaline sucrose gradients. DNA molecules corresponding to intact single-stranded virion DNA (50 x 10(6) daltons) were isolated and adjusted to neutral pH. The DNA was annealed under conditions permitting reassociation of intact single-stranded molecules and studied by electron microscopy. Three classes of DNA molecules showing double-stranded sequences were observed: (a) fully double-stranded DNA molecules the size of the intact HSV DNA genome, namely 52 micron; (b) DNA hybrids with a region of partial double-strandedness ranging from 5 to 12 micron, plus long single strands; and (c) DNA hybrids with a double-stranded region of 32--40 micron, plus short single strands. (These results suggest that the alkali-resistant single-stranded HSV DNA molecules are composed of several subclasses that permit annealing of either the total genome or the S or L components.) The 5 micron double-stranded region probably constitutes the S component of HSV DNA and the sequences longer than 5 micron and shorter than 12 micron represent annealing of the repeat sequences on either or both sides of the S component. The double-stranded sequences with a length of 32--40 micron may represent the L component. Treatment of the annealed, partially double-stranded hybrid DNA molecules with S1 endonuclease to remove the single-stranded termini and centrifugation in neutral sucrose gradients yielded two distinct peaks. Centrifugation of fractions from the two peaks in caesium chloride density gradients showed that the small DNA component (possibly the S and the repeat sequences) had a higher buoyant density and the longer (possibly the L) DNA component had a lower density than the HSV DNA marker. Annealing of alkali-resistant viral DNA strands therefore provides a means of isolating the L, S and repeat sequence regions of HSV DNA."}
{"id": "PMID:221328", "title": "Analysis of herpes simplex virus low molecular-weight native proteins by polyacrylamide gel electrofocusing.", "content": "This communication has demonstrated the potential application of gel electrofocusing for the isolation and further characterization of HSV-2 native proteins. At least eight major HSV-2 specific proteins with characteristic isoelectric points could be reproducibly resolved by gel isoelectric focusing. Their isoelectric points ranged from 5.0 to 7.5 and analysis by two-dimensional electrophoresis on SDS gels indicated that their molecular weights range from 11,000 to 49,000.", "contents": "Analysis of herpes simplex virus low molecular-weight native proteins by polyacrylamide gel electrofocusing. This communication has demonstrated the potential application of gel electrofocusing for the isolation and further characterization of HSV-2 native proteins. At least eight major HSV-2 specific proteins with characteristic isoelectric points could be reproducibly resolved by gel isoelectric focusing. Their isoelectric points ranged from 5.0 to 7.5 and analysis by two-dimensional electrophoresis on SDS gels indicated that their molecular weights range from 11,000 to 49,000."}
{"id": "PMID:221329", "title": "Crossed immunoelectrophoretic analysis and viral neutralizing activity of five monospecific antisera against five different herpes simplex virus glycoproteins.", "content": "Crossed immunoelectrophoresis of Triton X-100 solubilized HSV-infected cells has identified several major HSV glycoprotein antigens in the precipitating profile. Immunization of rabbits with the corresponding precipitates resulted in the production of monospecific antisera against the antigen part of the precipitate. The immunological importance of five different HSV glycoproteins in respect of their representation on the outer virion envelope as targets for neutralizing antibodies was evaluated by comparison of immunoprecipitating activity and neutralizing potency of the corresponding monospecific antisera.", "contents": "Crossed immunoelectrophoretic analysis and viral neutralizing activity of five monospecific antisera against five different herpes simplex virus glycoproteins. Crossed immunoelectrophoresis of Triton X-100 solubilized HSV-infected cells has identified several major HSV glycoprotein antigens in the precipitating profile. Immunization of rabbits with the corresponding precipitates resulted in the production of monospecific antisera against the antigen part of the precipitate. The immunological importance of five different HSV glycoproteins in respect of their representation on the outer virion envelope as targets for neutralizing antibodies was evaluated by comparison of immunoprecipitating activity and neutralizing potency of the corresponding monospecific antisera."}
{"id": "PMID:221331", "title": "Altered biological and biochemical properties of a phosphonoacetate-resistant mutant of herpesvirus of turkeys.", "content": "A phosphonoacetate (PA)-resistant mutant of the herpesvirus of turkeys (HVT) was isolated and characterized. The mutant (HVTpa) replicates in growth medium containing 300 microgram/ml of PA and shows in vitro temperature sensitivity at 41 degrees C (its 37 degrees C/41 degrees C efficiency of replication is about 5). HVTpa replicates poorly in chickens and fails to provide complete protection against MDV challenge. The HVTpa-induced DNA polymerase has an apparent inhibition constant for PA 10 times as great, an apparent inhibition constant for pyrophosphate, twice as great, and an apparent Michaelis constant for dCTP 2.5 times as great as the respective figures for the HVTwt-induced enzyme. The HVTpa-induced enzyme is also more thermolabile.", "contents": "Altered biological and biochemical properties of a phosphonoacetate-resistant mutant of herpesvirus of turkeys. A phosphonoacetate (PA)-resistant mutant of the herpesvirus of turkeys (HVT) was isolated and characterized. The mutant (HVTpa) replicates in growth medium containing 300 microgram/ml of PA and shows in vitro temperature sensitivity at 41 degrees C (its 37 degrees C/41 degrees C efficiency of replication is about 5). HVTpa replicates poorly in chickens and fails to provide complete protection against MDV challenge. The HVTpa-induced DNA polymerase has an apparent inhibition constant for PA 10 times as great, an apparent inhibition constant for pyrophosphate, twice as great, and an apparent Michaelis constant for dCTP 2.5 times as great as the respective figures for the HVTwt-induced enzyme. The HVTpa-induced enzyme is also more thermolabile."}
{"id": "PMID:221333", "title": "Regulation of herpes simplex virus type 1 DNA synthesis: temperature-shift studies with DNA-negative temperature-sensitive mutants.", "content": "The regulation of expression of viral genes involved in the synthesis of herpes simplex virus type 1 DNA was studied using three DNA- temperature-sensitive (ts) mutants (B, C, and D). These mutants were examined for their ability to synthesized viral DNA and polypeptides following temperature shift-down in the presence or absence of the transcription inhibitor actinomycin D. The results demonstrated that the B gene product is required transiently early in infection and apparently controls a transciptional step required for HSV DNA synthesis. The C gene product is required continuously during infection and also controls a transcriptional step needed for viral DNA synthesis. In contrast, the product of the D gene does not directly control a transcriptional step, is required continuously, appears to be directly involved in HSV DNA synthesis, and is probably the gene for viral DNA polymerase. The results further showed that recovery of viral DNA and polypeptide synthesis following temperature shift-down in the absence of inhibitor was greater for the D mutant than for the mutants blocked in viral DNA synthesis at the level of transcription.", "contents": "Regulation of herpes simplex virus type 1 DNA synthesis: temperature-shift studies with DNA-negative temperature-sensitive mutants. The regulation of expression of viral genes involved in the synthesis of herpes simplex virus type 1 DNA was studied using three DNA- temperature-sensitive (ts) mutants (B, C, and D). These mutants were examined for their ability to synthesized viral DNA and polypeptides following temperature shift-down in the presence or absence of the transcription inhibitor actinomycin D. The results demonstrated that the B gene product is required transiently early in infection and apparently controls a transciptional step required for HSV DNA synthesis. The C gene product is required continuously during infection and also controls a transcriptional step needed for viral DNA synthesis. In contrast, the product of the D gene does not directly control a transcriptional step, is required continuously, appears to be directly involved in HSV DNA synthesis, and is probably the gene for viral DNA polymerase. The results further showed that recovery of viral DNA and polypeptide synthesis following temperature shift-down in the absence of inhibitor was greater for the D mutant than for the mutants blocked in viral DNA synthesis at the level of transcription."}
{"id": "PMID:221335", "title": "Virus transcript mapping studies in cells infected with temperature-sensitive mutants of herpes simples virus type 1.", "content": "Nuclear and cytoplastic transcripts, synthesized in cells infected with six DNA-negative temperature-sensitive (ts) mutants of HSV-1 (ts B, ts D, ts E, ts K, ts S and ts T) under non-permissive conditions, were isolated and hybridized to unlabelled fragments of HSV-1 DNA, generated by restriction endonuclease digestion and immobilized on to nitrocellulose membranes by the method of Southern (1975). In this way it has been possible to map those regions of the HSV-1 genome represented by stable transcrips in cells infected with these mutants and compare them with those regions transcribed in cells infected with the wild-type virus at early and late times post infection (before and after viral DNA replication) and in the presence of DNA- and protein-synthesis inhibitors. Viral transcription in ts D, ts T and ts K-infected cells is restricted, the patterns of hybridization being similar, but not identical to that observed with immediate early RNA. Since these three mutants fall into two complementation groups, these experiments suggest that at least two viral products are required for the switch-on of early transcripts. In contrast, transcript mapping with the other early mutants (ts B, ts E and ts S) has shown a much less restricted transcriptional pattern, the pattern obtained resembling that with early, rather than late RNA.", "contents": "Virus transcript mapping studies in cells infected with temperature-sensitive mutants of herpes simples virus type 1. Nuclear and cytoplastic transcripts, synthesized in cells infected with six DNA-negative temperature-sensitive (ts) mutants of HSV-1 (ts B, ts D, ts E, ts K, ts S and ts T) under non-permissive conditions, were isolated and hybridized to unlabelled fragments of HSV-1 DNA, generated by restriction endonuclease digestion and immobilized on to nitrocellulose membranes by the method of Southern (1975). In this way it has been possible to map those regions of the HSV-1 genome represented by stable transcrips in cells infected with these mutants and compare them with those regions transcribed in cells infected with the wild-type virus at early and late times post infection (before and after viral DNA replication) and in the presence of DNA- and protein-synthesis inhibitors. Viral transcription in ts D, ts T and ts K-infected cells is restricted, the patterns of hybridization being similar, but not identical to that observed with immediate early RNA. Since these three mutants fall into two complementation groups, these experiments suggest that at least two viral products are required for the switch-on of early transcripts. In contrast, transcript mapping with the other early mutants (ts B, ts E and ts S) has shown a much less restricted transcriptional pattern, the pattern obtained resembling that with early, rather than late RNA."}
{"id": "PMID:221336", "title": "The regulations of gamma (structural) polypeptide synthesis in herpes simplex virus types 1 and 2 infected cells.", "content": "The polypeptides specified by herpes simplex viruses types 1 and 2 form at least three groups designated as alpha, beta and gamma. The structural polypeptides are largely contained in the gamma polypeptide group. In this study, we investigated the transition from beta to gamma polypeptide synthesis. Our data show the following: (i) gamma polypeptide synthesis in the presence of inhibitors of DNA synthesis in the presence of inhibitors of DNA synthesis is multiplicity-dependent. Some gamma polypeptides are not detectable in cells infected with 1 PFU per cell form a significant fraction of viral polypeptides in cells infected with 25--500 PFU per cell. (ii) The mRNAs specifying these polypeptides have a relatively short half-life as measured by the relative rate of decay of gamma polypeptide synthesis in infected cells following exposure to actinomycin D. Our data thus suggest that: (i) the transition from beta to gamma polypeptide synthesis does not require the synthesis of viral DNA; and (ii) the rate of synthesis of viral structural (gamma) polypeptides is linked to the size of the viral DNA pool as a consequence of a relatively short-lived mRNA.", "contents": "The regulations of gamma (structural) polypeptide synthesis in herpes simplex virus types 1 and 2 infected cells. The polypeptides specified by herpes simplex viruses types 1 and 2 form at least three groups designated as alpha, beta and gamma. The structural polypeptides are largely contained in the gamma polypeptide group. In this study, we investigated the transition from beta to gamma polypeptide synthesis. Our data show the following: (i) gamma polypeptide synthesis in the presence of inhibitors of DNA synthesis in the presence of inhibitors of DNA synthesis is multiplicity-dependent. Some gamma polypeptides are not detectable in cells infected with 1 PFU per cell form a significant fraction of viral polypeptides in cells infected with 25--500 PFU per cell. (ii) The mRNAs specifying these polypeptides have a relatively short half-life as measured by the relative rate of decay of gamma polypeptide synthesis in infected cells following exposure to actinomycin D. Our data thus suggest that: (i) the transition from beta to gamma polypeptide synthesis does not require the synthesis of viral DNA; and (ii) the rate of synthesis of viral structural (gamma) polypeptides is linked to the size of the viral DNA pool as a consequence of a relatively short-lived mRNA."}
{"id": "PMID:221337", "title": "Location of non-temperature-sensitive genes on the genetic map of herpes simplex virus type 1.", "content": "By constructing crosses involving the genes coding for the enzyme deoxypyrimidine kinase and for resistance to the drug phosphonoacetic acid, it has been possible both to extend the genetic analysis of HSV-1 such that the eight possible progeny genotypes which arise from a three-factor cross can be identified and also to precisely locate the gene for the plaque-morphology marker syn, the gene for deoxypyrimidine kinase dPYK and the gene for resistance to phosphonoacetic acid PAAr.", "contents": "Location of non-temperature-sensitive genes on the genetic map of herpes simplex virus type 1. By constructing crosses involving the genes coding for the enzyme deoxypyrimidine kinase and for resistance to the drug phosphonoacetic acid, it has been possible both to extend the genetic analysis of HSV-1 such that the eight possible progeny genotypes which arise from a three-factor cross can be identified and also to precisely locate the gene for the plaque-morphology marker syn, the gene for deoxypyrimidine kinase dPYK and the gene for resistance to phosphonoacetic acid PAAr."}
{"id": "PMID:221338", "title": "The thymidine kinase gene of herpes simplex virus type 1: cell-free protein synthesis and substrate specificity studies.", "content": "The HSV thymidine kinase genetic system has a number of advantages for the study of virus and cell genetics. Both forward and reverse mutants are readily selected. The enzyme can be assayed directly in the presence of the cell TK by the choice of the appropriate substrate, for example, 125IdC. The gene product, HSV TK, can be identified by SDS-polyacrylamide gel electrophoresis and mutants can be found with alterations in the electrophoretogram. The in vitro synthesis of HSV TK in response to HSV mRNA has been achieved and can be used to analyse specific mutant virus.", "contents": "The thymidine kinase gene of herpes simplex virus type 1: cell-free protein synthesis and substrate specificity studies. The HSV thymidine kinase genetic system has a number of advantages for the study of virus and cell genetics. Both forward and reverse mutants are readily selected. The enzyme can be assayed directly in the presence of the cell TK by the choice of the appropriate substrate, for example, 125IdC. The gene product, HSV TK, can be identified by SDS-polyacrylamide gel electrophoresis and mutants can be found with alterations in the electrophoretogram. The in vitro synthesis of HSV TK in response to HSV mRNA has been achieved and can be used to analyse specific mutant virus."}
{"id": "PMID:221339", "title": "Cell-free systems for in vitro translation of herpes simplex virus messenger RNA.", "content": "A cell-free system active in translation of HSV mRNA was obtained by fractionation of reticulocyte lysates. Endogenous protein synthesis was further reduced by preincubation with micrococcal nuclease, although this treatment did not affect the translation of infected (or uninfected) BHK cell RNA. Polypeptides synthesized by the fractionated reticulocyte cell-free system were very similar to those produced by unfractionated reticulocyte lysates.", "contents": "Cell-free systems for in vitro translation of herpes simplex virus messenger RNA. A cell-free system active in translation of HSV mRNA was obtained by fractionation of reticulocyte lysates. Endogenous protein synthesis was further reduced by preincubation with micrococcal nuclease, although this treatment did not affect the translation of infected (or uninfected) BHK cell RNA. Polypeptides synthesized by the fractionated reticulocyte cell-free system were very similar to those produced by unfractionated reticulocyte lysates."}
{"id": "PMID:221341", "title": "Analysis of viral gene functions by means of early temperature-sensitive mutants of human cytomegalovirus.", "content": "Fifteen ts mutants of CMV, which are unable to form normal plaques at 39 degrees C on HEL cells but do form plaques at 34 degrees C, have been isolated following mutagenesis by ultraviolet light. Five mutants defective in viral DNA synthesis at 39 degrees C were divided into two different complementation groups and examined for various phenotypic characteristics.", "contents": "Analysis of viral gene functions by means of early temperature-sensitive mutants of human cytomegalovirus. Fifteen ts mutants of CMV, which are unable to form normal plaques at 39 degrees C on HEL cells but do form plaques at 34 degrees C, have been isolated following mutagenesis by ultraviolet light. Five mutants defective in viral DNA synthesis at 39 degrees C were divided into two different complementation groups and examined for various phenotypic characteristics."}
{"id": "PMID:221342", "title": "Cell DNA induction by human cytomegalovirus.", "content": "The studies presented indicate that in cells pretreated with IUDR: (1) a temporal relationship exists between CMV and cell DNA synthesis; (2) in cells pretreated with IUDR only a fraction of the cell genome is induced by the virus to replicate; and (3) cell DNA induced by the virus to replicate represents unique rather than repetitive DNA sequences.", "contents": "Cell DNA induction by human cytomegalovirus. The studies presented indicate that in cells pretreated with IUDR: (1) a temporal relationship exists between CMV and cell DNA synthesis; (2) in cells pretreated with IUDR only a fraction of the cell genome is induced by the virus to replicate; and (3) cell DNA induced by the virus to replicate represents unique rather than repetitive DNA sequences."}
{"id": "PMID:221343", "title": "Effect of cyclic nucleotides on the response of cells to infection by various herpesviruses.", "content": "The effect of varying the intracellular cyclic nucleotide concentration of mouse cells infected with HSV-1 or of duck embryo fibroblasts infected with Marek's disease virus has been studied. It has been shown in each case that agents that elevate the intracellular cAMP levels increase the yield of infectious virus or viral DNA, but inhibit cell division. cGMP enhances synthesis of viral DNA but allows continued synthesis of cell DNA.", "contents": "Effect of cyclic nucleotides on the response of cells to infection by various herpesviruses. The effect of varying the intracellular cyclic nucleotide concentration of mouse cells infected with HSV-1 or of duck embryo fibroblasts infected with Marek's disease virus has been studied. It has been shown in each case that agents that elevate the intracellular cAMP levels increase the yield of infectious virus or viral DNA, but inhibit cell division. cGMP enhances synthesis of viral DNA but allows continued synthesis of cell DNA."}
{"id": "PMID:221345", "title": "Identification and partial purification of two EBV-associated DNA polymerases.", "content": "Virally induced DNA polymerases have been demonstrated in cells infected with a variety of herpesviruses. These include herpes simplex virus (Weissbach et al., 1973), Marek's disease virus (Boezi et al., 1974), equine herpesvirus (Allen et al., 1977), and cytomegalovirus (Huang, 1975a). Recently a new iododeoxyuridine (IUDR)-induced intracellular DNA polymerase in an Epstein-Barr virus (EBV)-producing hybrid cell line has also been reported (Miller et al., 1977). We present evidence that there are two different DNA polymerase activities associated with EBV, one intracellular and the other virion-associated. Both of these enzymes have certain biochemical characteristics which distinguish them from each other, and from the host-cell DNA polymerases found in lymphocytes.", "contents": "Identification and partial purification of two EBV-associated DNA polymerases. Virally induced DNA polymerases have been demonstrated in cells infected with a variety of herpesviruses. These include herpes simplex virus (Weissbach et al., 1973), Marek's disease virus (Boezi et al., 1974), equine herpesvirus (Allen et al., 1977), and cytomegalovirus (Huang, 1975a). Recently a new iododeoxyuridine (IUDR)-induced intracellular DNA polymerase in an Epstein-Barr virus (EBV)-producing hybrid cell line has also been reported (Miller et al., 1977). We present evidence that there are two different DNA polymerase activities associated with EBV, one intracellular and the other virion-associated. Both of these enzymes have certain biochemical characteristics which distinguish them from each other, and from the host-cell DNA polymerases found in lymphocytes."}
{"id": "PMID:221347", "title": "The use of intertypic recombinants for analysis of gene organization in herpes simplex virus.", "content": "Analysis of the DNA sequence arrangement and polypeptides specified by 28 HSV-1 x HSV-2 recombinants show the following: (i) Recombinants with heterogeneous L and S components or with heterogenous inverted repeats are viable. (ii) HSV-1 and HSV-2 genes appear to be functionally equivalent and with few exceptions co-linearly arranged. Co-linear DNA maps have been established. (iii) At most two arrangements of HSV DNA are capable of replication. This is consistant with current studies suggesting that sequence arrangements are the consequence of obligatory post-synthesis repair. (iv) alpha Polypeptides map at the termini of the L and S components of HSV DNA. Although alpha ICP 27 maps entirely within the reiterated region of the L component, the template for alpha ICP 4 may lie only in part within the reiterated sequences of the S component. Of note is the finding that cells infected with a recombinant that contains both HSV-1 and HSV-2 DNA sequences in the S component, produced alpha ICP 4 of both HSV-1 and HSV-2. (v) Templates specifying beta and gamma polypeptides may in the L component and appear to be randomly distributed. (vi) The genes specifying thymidine kinase, resistance to phosphonoacetic acid and syncytial plaque morphology mapped in the L component. In addition, we have taken advantage of the rapid inhibition of host protein synthesis to map the gene(s) specifying this inhibition in the L component.", "contents": "The use of intertypic recombinants for analysis of gene organization in herpes simplex virus. Analysis of the DNA sequence arrangement and polypeptides specified by 28 HSV-1 x HSV-2 recombinants show the following: (i) Recombinants with heterogeneous L and S components or with heterogenous inverted repeats are viable. (ii) HSV-1 and HSV-2 genes appear to be functionally equivalent and with few exceptions co-linearly arranged. Co-linear DNA maps have been established. (iii) At most two arrangements of HSV DNA are capable of replication. This is consistant with current studies suggesting that sequence arrangements are the consequence of obligatory post-synthesis repair. (iv) alpha Polypeptides map at the termini of the L and S components of HSV DNA. Although alpha ICP 27 maps entirely within the reiterated region of the L component, the template for alpha ICP 4 may lie only in part within the reiterated sequences of the S component. Of note is the finding that cells infected with a recombinant that contains both HSV-1 and HSV-2 DNA sequences in the S component, produced alpha ICP 4 of both HSV-1 and HSV-2. (v) Templates specifying beta and gamma polypeptides may in the L component and appear to be randomly distributed. (vi) The genes specifying thymidine kinase, resistance to phosphonoacetic acid and syncytial plaque morphology mapped in the L component. In addition, we have taken advantage of the rapid inhibition of host protein synthesis to map the gene(s) specifying this inhibition in the L component."}
{"id": "PMID:221351", "title": "Mapping of the herpes simplex virus DNA sequences in three herpes simplex virus thymidine kinase-transformed cell lines.", "content": "We have made use of a novel filter hybridization approach in order to map the herpes simplex virus (HSV) DNA sequences which are present in three HSV thymidine kinase (TK)-transformed cell lines. The cell line 33A+ which was produced by infection of 3T3 TK- cells with UV-irradiated HSV-2 (333) was found to contain one contiguous stretch of viral DNA sequences which maps between 0.15 and 0.57 on the HSV-2 genome. The sequences mapping from 0.31 to 0.37 were present in 3--4-fold higher abundance than the rest of the viral DNA sequences in this cell line. Cell lines 5A and 8N were produced by transfection of mouse CL1D cells with sheared HSV-1 (1023) DNA. The cell line 5A was found to contain a contiguous set of viral DNA sequences mapping between 0.26 and 0.41 on the HSV-1 genome. The cell line 8N was found to contain three non-contiguous sets of viral DNA sequences, mapping between 0.09 and 0.41, 0.53 and 0.58, and 0.94 and 1.0 on the HSV-1 genome. These results seem to indicate that many different sets of viral DNA sequences can be incorporated into the cell during HSV-mediated biochemical transformation.", "contents": "Mapping of the herpes simplex virus DNA sequences in three herpes simplex virus thymidine kinase-transformed cell lines. We have made use of a novel filter hybridization approach in order to map the herpes simplex virus (HSV) DNA sequences which are present in three HSV thymidine kinase (TK)-transformed cell lines. The cell line 33A+ which was produced by infection of 3T3 TK- cells with UV-irradiated HSV-2 (333) was found to contain one contiguous stretch of viral DNA sequences which maps between 0.15 and 0.57 on the HSV-2 genome. The sequences mapping from 0.31 to 0.37 were present in 3--4-fold higher abundance than the rest of the viral DNA sequences in this cell line. Cell lines 5A and 8N were produced by transfection of mouse CL1D cells with sheared HSV-1 (1023) DNA. The cell line 5A was found to contain a contiguous set of viral DNA sequences mapping between 0.26 and 0.41 on the HSV-1 genome. The cell line 8N was found to contain three non-contiguous sets of viral DNA sequences, mapping between 0.09 and 0.41, 0.53 and 0.58, and 0.94 and 1.0 on the HSV-1 genome. These results seem to indicate that many different sets of viral DNA sequences can be incorporated into the cell during HSV-mediated biochemical transformation."}
{"id": "PMID:221353", "title": "DNA-mediated transfer of herpes simplex virus TK gene to human TK- cells: properties of the transformed lines.", "content": "Human TK- cells carrying the HSV-2 TK gene express a TK activity of viral origin and maintain the TK+ phenotype when grown in HAT medium. Under non-selective or counterselective conditions, however, reversion to a TK- phenotype occurs with a significant frequency characteristic of each transformed line. The TK- phenotype appears to be stable since no instances of TK- to TK+ reversion have been observed.", "contents": "DNA-mediated transfer of herpes simplex virus TK gene to human TK- cells: properties of the transformed lines. Human TK- cells carrying the HSV-2 TK gene express a TK activity of viral origin and maintain the TK+ phenotype when grown in HAT medium. Under non-selective or counterselective conditions, however, reversion to a TK- phenotype occurs with a significant frequency characteristic of each transformed line. The TK- phenotype appears to be stable since no instances of TK- to TK+ reversion have been observed."}
{"id": "PMID:221355", "title": "Oncogenic transformation of non-permissive murine cells by viable equine herpesvirus type 1 (EHV-1) and EHV-1 DNA.", "content": "Primary cultures of BALB/c mouse embryo fibroblasts infected with as much as 100 PFU per cell of EHV-1 do not exhibit cytopathology or synthesize detectable amounts of EHV-1 specific RNA, DNA, or infectious virus. Addition of 1--2 microgram of non-fragmented EHV-1 DNA as a co-precipitate with calcium phosphate to monolayers of such non-permissive mouse cells resulted in the appearance, after 4--6 weeks, of foci of piled-up, morphologically altered cells. Cell lines established from such transformed foci exhibited a greatly increased growth rate, unlimited growth potential, aneuploid karyotype, and grew with colony formation in soft agar. Inoculation of 10(6) transformed cells into newborn syngeneic mice resulted in the formation of serially transplantable tumours (undifferentiated fibrosarcomas) with a 100% incidence within eight weeks. Infectious virus could not be rescued from the EHV-1 transformed or tumour-derived cell lines by growth in the presence of IUDR, by cocultivation with permissive horse cells, or by attempts to transfect permissive cells with transformed or tumour cell DNA. However, EHV-1 specific membrane antigens were detected in the transformed cells by immunofluorescence with hyperimmune anti-EHV-1 mouse serum, and the presence of a fragment of the EHV-1 genome was demonstrated in both the transformed and tumour cells. These results indicate that cells nonpermissive for replication of EHV-1 remain susceptible to neoplastic transformation by the EHV-1 genome.", "contents": "Oncogenic transformation of non-permissive murine cells by viable equine herpesvirus type 1 (EHV-1) and EHV-1 DNA. Primary cultures of BALB/c mouse embryo fibroblasts infected with as much as 100 PFU per cell of EHV-1 do not exhibit cytopathology or synthesize detectable amounts of EHV-1 specific RNA, DNA, or infectious virus. Addition of 1--2 microgram of non-fragmented EHV-1 DNA as a co-precipitate with calcium phosphate to monolayers of such non-permissive mouse cells resulted in the appearance, after 4--6 weeks, of foci of piled-up, morphologically altered cells. Cell lines established from such transformed foci exhibited a greatly increased growth rate, unlimited growth potential, aneuploid karyotype, and grew with colony formation in soft agar. Inoculation of 10(6) transformed cells into newborn syngeneic mice resulted in the formation of serially transplantable tumours (undifferentiated fibrosarcomas) with a 100% incidence within eight weeks. Infectious virus could not be rescued from the EHV-1 transformed or tumour-derived cell lines by growth in the presence of IUDR, by cocultivation with permissive horse cells, or by attempts to transfect permissive cells with transformed or tumour cell DNA. However, EHV-1 specific membrane antigens were detected in the transformed cells by immunofluorescence with hyperimmune anti-EHV-1 mouse serum, and the presence of a fragment of the EHV-1 genome was demonstrated in both the transformed and tumour cells. These results indicate that cells nonpermissive for replication of EHV-1 remain susceptible to neoplastic transformation by the EHV-1 genome."}
{"id": "PMID:221357", "title": "Enhanced efficiency of transfection of HSV DNA in HSV-1 DNA-transformed hamster cells.", "content": "The efficiency of transfection, i.e., the number of plaques per microgram of DNA, was compared for herpes simplex virus (HSV) type 1 and type 2, and herpesvirus eidolon (antigenically unrelated to HSV) DNAs in HSV DNA-transformed cells (EH/A44) and control hamster cells (EHT). The efficiency of transfection of HSV-1 and HSV-2 DNAs was significantly higher in EH/A44 cells than in EHT cells, showing that an early step in HSV infection was involved in the partial resistance of HSV DNA-transformed cells to superinfection by various intact herpesviruses.", "contents": "Enhanced efficiency of transfection of HSV DNA in HSV-1 DNA-transformed hamster cells. The efficiency of transfection, i.e., the number of plaques per microgram of DNA, was compared for herpes simplex virus (HSV) type 1 and type 2, and herpesvirus eidolon (antigenically unrelated to HSV) DNAs in HSV DNA-transformed cells (EH/A44) and control hamster cells (EHT). The efficiency of transfection of HSV-1 and HSV-2 DNAs was significantly higher in EH/A44 cells than in EHT cells, showing that an early step in HSV infection was involved in the partial resistance of HSV DNA-transformed cells to superinfection by various intact herpesviruses."}
{"id": "PMID:221358", "title": "Mapping of putative transforming sequences of EBV DNA.", "content": "The linkage of restriction enzyme fragments of DNA of the B95-8 strain of Epstein-Barr virus has been determined. Two approaches are being employed to define which EBV DNA sequences are needed to initiate and maintain the transformation of lymphocytes to lymphoblasts capable of long-term growth in culture. The first approach is to determine the differences between the DNA of strains of EBV which possess transforming capacity and the DNA of the HR-1 strain which cannot transform. The data indicate that EBV (HR-1) DNA lacks approximately 2--3 x 10(6) daltons of DNA contained largely in the HsuI B and EcoRI (J-K) and A fragments of EBV (B95-8) DNA and in the EcoRI A and HsuI B fragment of the W91 strain. The DNA common to HsuI B and EcoRI A fragments lies between 27 and 42 x 10(6) daltons from the HsuI A end of the molecule. This finding is compatible with the hypothesis that the inability of the HR-1 strain to transform is due to the absence of DNA needed for transformation. The second approach is to identify and map the DNA encoding polyadenylated viral RNA in cultures of restringently infected cells which contain the EBNA antigen and show no evidence of abortive or productive infection. Previous data indicated that viral RNA species encoded by 5% of the viral DNA are adenylated and identified in the polyribosomes of restringently infected cells. The data indicate that these RNAs are encoded primarily by the HsuI A (and to a lesser extent, B) fragment of EBV (B95-8) DNA. This would place the DNA encoding the viral RNA processed in restrigently infected cells adjacent to and possibly overlapping the small DNA segment deleted from the DNA of the non-transforming HR-1 strain.", "contents": "Mapping of putative transforming sequences of EBV DNA. The linkage of restriction enzyme fragments of DNA of the B95-8 strain of Epstein-Barr virus has been determined. Two approaches are being employed to define which EBV DNA sequences are needed to initiate and maintain the transformation of lymphocytes to lymphoblasts capable of long-term growth in culture. The first approach is to determine the differences between the DNA of strains of EBV which possess transforming capacity and the DNA of the HR-1 strain which cannot transform. The data indicate that EBV (HR-1) DNA lacks approximately 2--3 x 10(6) daltons of DNA contained largely in the HsuI B and EcoRI (J-K) and A fragments of EBV (B95-8) DNA and in the EcoRI A and HsuI B fragment of the W91 strain. The DNA common to HsuI B and EcoRI A fragments lies between 27 and 42 x 10(6) daltons from the HsuI A end of the molecule. This finding is compatible with the hypothesis that the inability of the HR-1 strain to transform is due to the absence of DNA needed for transformation. The second approach is to identify and map the DNA encoding polyadenylated viral RNA in cultures of restringently infected cells which contain the EBNA antigen and show no evidence of abortive or productive infection. Previous data indicated that viral RNA species encoded by 5% of the viral DNA are adenylated and identified in the polyribosomes of restringently infected cells. The data indicate that these RNAs are encoded primarily by the HsuI A (and to a lesser extent, B) fragment of EBV (B95-8) DNA. This would place the DNA encoding the viral RNA processed in restrigently infected cells adjacent to and possibly overlapping the small DNA segment deleted from the DNA of the non-transforming HR-1 strain."}
{"id": "PMID:221359", "title": "In vitro lymphocyte transformation by Epstein-Barr virus (EBV)-like viruses isolated from Old-World non-human primates.", "content": "EBV-like viruses and lymphoid cell lines have been isolated from baboons and an orangutan. The cell lines have properties of B- or undifferentiated lymphocytes and have antigens and DNA related to those of EBV. The baboon virus has a broad in vitro transformation host range among lymphocytes of Old-World simian species whereas the orangutan isolate has a narrower host range. Baboon and orangutan viruses as well as EBV have shown transforming activity for gibbon lymphocytes. Baboon virus is infectious for rhesus monkeys and baboons but has not induced neoplastic disease in these species.", "contents": "In vitro lymphocyte transformation by Epstein-Barr virus (EBV)-like viruses isolated from Old-World non-human primates. EBV-like viruses and lymphoid cell lines have been isolated from baboons and an orangutan. The cell lines have properties of B- or undifferentiated lymphocytes and have antigens and DNA related to those of EBV. The baboon virus has a broad in vitro transformation host range among lymphocytes of Old-World simian species whereas the orangutan isolate has a narrower host range. Baboon and orangutan viruses as well as EBV have shown transforming activity for gibbon lymphocytes. Baboon virus is infectious for rhesus monkeys and baboons but has not induced neoplastic disease in these species."}
{"id": "PMID:221360", "title": "Transcription of Epstein-Barr virus genomes in human lymphoblastoid cells and in somatic-cell hybrids of Burkitt's lymphoma.", "content": "Expression of latent Epstein-Barr virus genomes in lymphoblastoid cells and somatic-cell hybrid of Burkitt's lymphoblastoid cells has been studied. IUDR treatment induced the formation of early antigen (EA), virus capsid antigen (VCA) and virus DNA replication in D98/Raji and D98/HR-1 cells whereas only EA was induced in Raji cells. HR-1 clone No. 9 did not respond to IUDR treatment. The pattern of transcription of virus genomes in these cell lines without IUDR treatment was uniform with 20--25% of virus DNA transcribed. IUDR treatment enhanced the transcription of virus DNA to 50% in D98/Raji, D98/HR-1 and Raji cells but no enhancement of virus genome transcription was observed in HR-1 clone No. 9 The amount of virus RNA in the cells calculated from DNA-RNA hybridization kinetics was found to be proportional to the number of virus genomes per cell indicating that every copy of virus DNA in these cells is actively transcribed.", "contents": "Transcription of Epstein-Barr virus genomes in human lymphoblastoid cells and in somatic-cell hybrids of Burkitt's lymphoma. Expression of latent Epstein-Barr virus genomes in lymphoblastoid cells and somatic-cell hybrid of Burkitt's lymphoblastoid cells has been studied. IUDR treatment induced the formation of early antigen (EA), virus capsid antigen (VCA) and virus DNA replication in D98/Raji and D98/HR-1 cells whereas only EA was induced in Raji cells. HR-1 clone No. 9 did not respond to IUDR treatment. The pattern of transcription of virus genomes in these cell lines without IUDR treatment was uniform with 20--25% of virus DNA transcribed. IUDR treatment enhanced the transcription of virus DNA to 50% in D98/Raji, D98/HR-1 and Raji cells but no enhancement of virus genome transcription was observed in HR-1 clone No. 9 The amount of virus RNA in the cells calculated from DNA-RNA hybridization kinetics was found to be proportional to the number of virus genomes per cell indicating that every copy of virus DNA in these cells is actively transcribed."}
{"id": "PMID:221361", "title": "Studies on the association of the Epstein-Barr virus genome with chromosomes in human (Burkitt)/mouse hybrid cells.", "content": "We have used somatic-cell hybrids of mouse fibroblast and Burkitt's lymphoblastoid tumour cells to continue our investigation of the association between Epstein-Barr virus (EBV) genome and human chromosomes. A mouse/Burkitt hybrid cell, designated CL1D/HR-1, was cloned in soft agar. Each of 10 clones was assayed for the spontaneous expression of EBV-associated nuclear antigen (EBNA), early antigen (EA) and virus capsid antigen (VCA). Six of 10 clones were EBNA-positive but negative for EA and VCA even after treatment with iododeoxyuridine. One clone, designated M44, contained approximately 90% EBNA-positive cells and 0.3--0.5 EBV genome equivalents per cell. Thirty subclones of clone M44 were obtained and analysed for EBV DNA, EBNA and human chromosomes. Four subclones (three EBNA-positive and one EBNA-negative) were studied in detail. Data obtained thus far indicate that none of the four subclones of clone M44 studied contained any intact human chromosome. Isozyme analysis of these subclones indicated that all four subclones, regardless of the status of the EBV genome, synthesized nucleoside phosphorylase, an enzyme which has been linked to human chromosome number 14.", "contents": "Studies on the association of the Epstein-Barr virus genome with chromosomes in human (Burkitt)/mouse hybrid cells. We have used somatic-cell hybrids of mouse fibroblast and Burkitt's lymphoblastoid tumour cells to continue our investigation of the association between Epstein-Barr virus (EBV) genome and human chromosomes. A mouse/Burkitt hybrid cell, designated CL1D/HR-1, was cloned in soft agar. Each of 10 clones was assayed for the spontaneous expression of EBV-associated nuclear antigen (EBNA), early antigen (EA) and virus capsid antigen (VCA). Six of 10 clones were EBNA-positive but negative for EA and VCA even after treatment with iododeoxyuridine. One clone, designated M44, contained approximately 90% EBNA-positive cells and 0.3--0.5 EBV genome equivalents per cell. Thirty subclones of clone M44 were obtained and analysed for EBV DNA, EBNA and human chromosomes. Four subclones (three EBNA-positive and one EBNA-negative) were studied in detail. Data obtained thus far indicate that none of the four subclones of clone M44 studied contained any intact human chromosome. Isozyme analysis of these subclones indicated that all four subclones, regardless of the status of the EBV genome, synthesized nucleoside phosphorylase, an enzyme which has been linked to human chromosome number 14."}
{"id": "PMID:221363", "title": "Characterization of the replicative structures of the DNA of a herpesvirus (pseudorabies).", "content": "The replication of PRV DNA occurs in two phases, early and late. During the early stages of infection newly synthesized DNA is associated with molecules sedimenting with an S-value up to two-fold greater than that of mature viral DNA. These molecules represent unit-size linear or circular molecules, as well as small concatemers in the process of replication. Initiation of replication occurs at a site situated 20 micron from one of the ends as well as at or near the end of the molecules. At later times, newly synthesized DNA is associated with large, \"tangled\" concatemers containing single-stranded segments of DNA. Our results indicate that at least some of the single-stranded DNA may be produced during the extraction procedure. Analysis of the large, \"tangled\" concatemers with restriction enzymes shows that they consist of linear arrays of viral DNA molecules.", "contents": "Characterization of the replicative structures of the DNA of a herpesvirus (pseudorabies). The replication of PRV DNA occurs in two phases, early and late. During the early stages of infection newly synthesized DNA is associated with molecules sedimenting with an S-value up to two-fold greater than that of mature viral DNA. These molecules represent unit-size linear or circular molecules, as well as small concatemers in the process of replication. Initiation of replication occurs at a site situated 20 micron from one of the ends as well as at or near the end of the molecules. At later times, newly synthesized DNA is associated with large, \"tangled\" concatemers containing single-stranded segments of DNA. Our results indicate that at least some of the single-stranded DNA may be produced during the extraction procedure. Analysis of the large, \"tangled\" concatemers with restriction enzymes shows that they consist of linear arrays of viral DNA molecules."}
{"id": "PMID:221364", "title": "The DNA of serially passaged herpes simplex virus: organization, origin, and homology to viral RNA.", "content": "High-density DNA prepared from serially passaged herpes simplex virus contains three major classes of modified viral DNA molecules. The altered DNA molecules are composed of multiple repetitions of sequences derived from the right-hand side of the S region of the parental plaque-purified viral DNA. The repeat units contained in the three types of high-density DNA share most of their DNA sequences but differ with respect to a small region derived from the unique sequences of the S component of HSV-1 DNA. Hybridization of the defective DNA to HSV-infected cell RNA shows that the high-density DNA contains sequences complementary to both early and late viral transcripts.", "contents": "The DNA of serially passaged herpes simplex virus: organization, origin, and homology to viral RNA. High-density DNA prepared from serially passaged herpes simplex virus contains three major classes of modified viral DNA molecules. The altered DNA molecules are composed of multiple repetitions of sequences derived from the right-hand side of the S region of the parental plaque-purified viral DNA. The repeat units contained in the three types of high-density DNA share most of their DNA sequences but differ with respect to a small region derived from the unique sequences of the S component of HSV-1 DNA. Hybridization of the defective DNA to HSV-infected cell RNA shows that the high-density DNA contains sequences complementary to both early and late viral transcripts."}
{"id": "PMID:221365", "title": "Characterization of human varicella-zoster virus DNA.", "content": "The DNA of varicella-zoster virus (VZV) has been characterized by sucrose gradient sedimentation, restriction enzyme cleavage with either EcoRI or HindIII site-specific endonucleases, and by isopycnic banding in caesium chloride. Comparisons of the DNAs from different clinical isolates have been made. DNAs from VZVs isolated from either varicella or herpes zoster are indistinguishable on the basis of size and restriction enzyme cleavage pattern. The buoyant density in caesium chloride of the DNA of VZV isolated from varicella was reproducibly slightly lower than that of the DNA of VZV isolated from herpes zoster.", "contents": "Characterization of human varicella-zoster virus DNA. The DNA of varicella-zoster virus (VZV) has been characterized by sucrose gradient sedimentation, restriction enzyme cleavage with either EcoRI or HindIII site-specific endonucleases, and by isopycnic banding in caesium chloride. Comparisons of the DNAs from different clinical isolates have been made. DNAs from VZVs isolated from either varicella or herpes zoster are indistinguishable on the basis of size and restriction enzyme cleavage pattern. The buoyant density in caesium chloride of the DNA of VZV isolated from varicella was reproducibly slightly lower than that of the DNA of VZV isolated from herpes zoster."}
{"id": "PMID:221366", "title": "Characterization of human cytomegalovirus DNA: infectivity and molecular weight.", "content": "Human cytomegalovirus DNA was isolated from purified virions and further purified by sucrose density-gradient centrifugation. The viral DNA molecules were studied by electron microscopy and found to be linear and to have a length of 76.22 +/- 3.80 microM, corresponding to a molecular weight of 147.13 +/- 6.18 x 10(6). The DNA was infectious when tested in human embryonic lung cells using the DEAE-dextran and the calcium-phosphate techniques. The density in caesium chloride was 1.717 g/cm3.", "contents": "Characterization of human cytomegalovirus DNA: infectivity and molecular weight. Human cytomegalovirus DNA was isolated from purified virions and further purified by sucrose density-gradient centrifugation. The viral DNA molecules were studied by electron microscopy and found to be linear and to have a length of 76.22 +/- 3.80 microM, corresponding to a molecular weight of 147.13 +/- 6.18 x 10(6). The DNA was infectious when tested in human embryonic lung cells using the DEAE-dextran and the calcium-phosphate techniques. The density in caesium chloride was 1.717 g/cm3."}
{"id": "PMID:221368", "title": "Inhibition of the multiplication of herpes simplex virus by aliphatic nitrosamines.", "content": "Non-toxic doses of dimethylnitrosamine and diethylnitrosamine inhibit the multiplication of herpes simplex virus type 1 and type 2 in HEp-2, Wi-38 and primary HEK cells. These results are somewhat unexpected, since both HEp-2 and Wi-38 cells lack detectable microsomal enzyme activity. The possible significance of the preliminary results is discussed.", "contents": "Inhibition of the multiplication of herpes simplex virus by aliphatic nitrosamines. Non-toxic doses of dimethylnitrosamine and diethylnitrosamine inhibit the multiplication of herpes simplex virus type 1 and type 2 in HEp-2, Wi-38 and primary HEK cells. These results are somewhat unexpected, since both HEp-2 and Wi-38 cells lack detectable microsomal enzyme activity. The possible significance of the preliminary results is discussed."}
{"id": "PMID:221369", "title": "Potential for immunization against herpesvirus infections with plasma membrane vesicles.", "content": "Virus-free, membrane antigen (MA)-positive plasma membrane vesicles produced from herpesvirus saimiri-infected owl monkey cells were used as immunogens in cotton-top marmosets. Neutralizing antibodies as well as antibodies to MA and HVS-induced LA were induced following immunization of marmosets with these vesicles. Preliminary findings demonstrated that immunized marmosets were significantly less susceptible to tumour induction by HVS than control animals.", "contents": "Potential for immunization against herpesvirus infections with plasma membrane vesicles. Virus-free, membrane antigen (MA)-positive plasma membrane vesicles produced from herpesvirus saimiri-infected owl monkey cells were used as immunogens in cotton-top marmosets. Neutralizing antibodies as well as antibodies to MA and HVS-induced LA were induced following immunization of marmosets with these vesicles. Preliminary findings demonstrated that immunized marmosets were significantly less susceptible to tumour induction by HVS than control animals."}
{"id": "PMID:221370", "title": "Herpes simplex virus vaccine: protection from stomatitis, ganglionitis, encephalitis and latency.", "content": "A mouse model system was developed for studying the pathogenesis of oral infection with herpes simplex virus type 1 and the protection offered by prior immunization with a nucleic acid-free vaccine. Of non-immunized mice, 95-100% developed ulcerative lesions 3-5 days following application of virus to abraded oral epithelial surfaces. Infection of the ipsilateral sensory (trigeminal) ganglion and the cerebellum occurred by day 2 and sequentially progressed to the contralateral ganglion by day 4 and to the cerebrum by day 5. Prior immunization of mice with an inactivated virus vaccine, and most importantly, with a vaccine free of nucleic acid, protected mice from subsequent oral virus infection. Protection was demonstrated by: (i) reduction in the incidence and severity of primary oral lesions; (ii) a decrease in the number of mice with acute ganglionic infection or dying of encephalitis; and (iii) a reduction in the incidence of latent trigeminal ganglionic infection.", "contents": "Herpes simplex virus vaccine: protection from stomatitis, ganglionitis, encephalitis and latency. A mouse model system was developed for studying the pathogenesis of oral infection with herpes simplex virus type 1 and the protection offered by prior immunization with a nucleic acid-free vaccine. Of non-immunized mice, 95-100% developed ulcerative lesions 3-5 days following application of virus to abraded oral epithelial surfaces. Infection of the ipsilateral sensory (trigeminal) ganglion and the cerebellum occurred by day 2 and sequentially progressed to the contralateral ganglion by day 4 and to the cerebrum by day 5. Prior immunization of mice with an inactivated virus vaccine, and most importantly, with a vaccine free of nucleic acid, protected mice from subsequent oral virus infection. Protection was demonstrated by: (i) reduction in the incidence and severity of primary oral lesions; (ii) a decrease in the number of mice with acute ganglionic infection or dying of encephalitis; and (iii) a reduction in the incidence of latent trigeminal ganglionic infection."}
{"id": "PMID:221371", "title": "A live varicella vaccine used for children in hospitals.", "content": "A live varicella vaccine was developed and the following results obtained: 1. The vaccine was safely and effectively used for children in hospital with various underlying diseases; some of the children had been receiving immunosuppressive therapy. 2. Spread of varicella could be prevented by immediate inoculation of the vaccine in hospital or at home when vaccine was given to susceptible children within 72 hours after exposure. 3. Persistence of neutralizing antibody and prevention of natural varicella have been confirmed in a two-year follow-up study of the vaccine recipients. 4. No contact infection from vaccine recipients to susceptible children in closed institutions was detected (Asano et al., 1976). 5. Varicella skin antigen was prepared and was found useful for clinical purposes, e.g., by providing a convenient means of determining the susceptibility of individuals to clinical varicella.", "contents": "A live varicella vaccine used for children in hospitals. A live varicella vaccine was developed and the following results obtained: 1. The vaccine was safely and effectively used for children in hospital with various underlying diseases; some of the children had been receiving immunosuppressive therapy. 2. Spread of varicella could be prevented by immediate inoculation of the vaccine in hospital or at home when vaccine was given to susceptible children within 72 hours after exposure. 3. Persistence of neutralizing antibody and prevention of natural varicella have been confirmed in a two-year follow-up study of the vaccine recipients. 4. No contact infection from vaccine recipients to susceptible children in closed institutions was detected (Asano et al., 1976). 5. Varicella skin antigen was prepared and was found useful for clinical purposes, e.g., by providing a convenient means of determining the susceptibility of individuals to clinical varicella."}
{"id": "PMID:221372", "title": "Non-protective variants of Marek's disease vaccine viruses.", "content": "Two variant Marek's disease-vaccine viruses failed to induce protective immune responses in chickens and replicated poorly in vivo. One of these, MDV/200D, was defective for growth at 41 degrees C, and clones from this stock had 38 degrees C/41 degrees C plating ratios as high as 10(4). The basis for the poor in vivo replicative ability was not determined.", "contents": "Non-protective variants of Marek's disease vaccine viruses. Two variant Marek's disease-vaccine viruses failed to induce protective immune responses in chickens and replicated poorly in vivo. One of these, MDV/200D, was defective for growth at 41 degrees C, and clones from this stock had 38 degrees C/41 degrees C plating ratios as high as 10(4). The basis for the poor in vivo replicative ability was not determined."}
{"id": "PMID:221373", "title": "Interferon in the replication of herpes simplex virus in normal and pathological nerve cells.", "content": "Previous results obtained in experimental and clinical trials have demonstrated that topical combined thrapy with human interferon (HI) and human colostral secretory immunoglobulin A (S-IgA) is effective against herpetic corneal infection. This therapy prevented encephalitis in rabbits but could not completely prevent recurrences either in rabbits or in patients. A number of in vitro studies were designed to elucidate the role of these factors in herpes simplex virus replication in the nervous system, with the following results: (1) HSV latency in trigeminal ganglia (TG) explanted from rabbits with experimental herpetic keratitis, topically treated with HI or HI/S-IgA: HSV was recovered in 30% TG after 15-19 days co-cultivation on RK-13 cells. (2) HSV replication in nervous ganglia and nerve of newborn rabbits in organ culture; influence of HI or HI plus IgG: a restrictive HSV productive infection was demonstrated in this system, although yields were always higher in nerve cultures. We were unable to demonstrate a direct effect of HI on HSV-1 replication. When explants were treated with HI and IgG before and after infection for 48 hours a delay in the expression of HSV-1 was detected by co-cultivation. (3) Replication of HSV-1 and HSV-2 in a C1300 murine neuroblastoma clone (NB41A3): both HSV types replicated with titres of 10(3.4) for HSV-1 AND 10(4.8) for HSV-2 at 48 hours p.i.; CPE was more marked for HSV-2 at 24 hours. HSV-specific antigens were demonstrated by the immunoperoxidase technique.", "contents": "Interferon in the replication of herpes simplex virus in normal and pathological nerve cells. Previous results obtained in experimental and clinical trials have demonstrated that topical combined thrapy with human interferon (HI) and human colostral secretory immunoglobulin A (S-IgA) is effective against herpetic corneal infection. This therapy prevented encephalitis in rabbits but could not completely prevent recurrences either in rabbits or in patients. A number of in vitro studies were designed to elucidate the role of these factors in herpes simplex virus replication in the nervous system, with the following results: (1) HSV latency in trigeminal ganglia (TG) explanted from rabbits with experimental herpetic keratitis, topically treated with HI or HI/S-IgA: HSV was recovered in 30% TG after 15-19 days co-cultivation on RK-13 cells. (2) HSV replication in nervous ganglia and nerve of newborn rabbits in organ culture; influence of HI or HI plus IgG: a restrictive HSV productive infection was demonstrated in this system, although yields were always higher in nerve cultures. We were unable to demonstrate a direct effect of HI on HSV-1 replication. When explants were treated with HI and IgG before and after infection for 48 hours a delay in the expression of HSV-1 was detected by co-cultivation. (3) Replication of HSV-1 and HSV-2 in a C1300 murine neuroblastoma clone (NB41A3): both HSV types replicated with titres of 10(3.4) for HSV-1 AND 10(4.8) for HSV-2 at 48 hours p.i.; CPE was more marked for HSV-2 at 24 hours. HSV-specific antigens were demonstrated by the immunoperoxidase technique."}
{"id": "PMID:221374", "title": "Effect of exogenous interferon on neonatal infection with murine cytomegalovirus.", "content": "One dose of interferon given before inoculation of MCMV to the neonatal mouse resulted in less virus in the submaxillary glands and reduced tissue damage due to MCMV infection, probably by modulating the immune system.", "contents": "Effect of exogenous interferon on neonatal infection with murine cytomegalovirus. One dose of interferon given before inoculation of MCMV to the neonatal mouse resulted in less virus in the submaxillary glands and reduced tissue damage due to MCMV infection, probably by modulating the immune system."}
{"id": "PMID:221382", "title": "Alterations in biological properties of different lines of cytomegalorivus-transformed human embryo lung cells following in vitro cultivation.", "content": "Diverse alterations in biological properties of CMV-transformed cell lines were observed during prolonged in vitro cultivation. In the CMV-Mj-HEL-2 parent line there was a gradual decrease in the number of cells expressing CMV-related antigens; at the same time, an increase in oncogenicity was observed. One tumour line, designated CMV-Mj-HEL-2,T-1, however, retained the original ratio of cells expressing CMV-related antigens for over 100 in vitro passages. The cells lost their original moderate oncogenicity during this period. A later increase in the ratio of cells without CMV antigenic markers was accompanied by the return of moderate tumorigenicity and karyotypic changes. Both cell lines were studied to determine sensitivity to superinfection with herpesviruses, induction of immune response in nude mice, and release of infectious virus.", "contents": "Alterations in biological properties of different lines of cytomegalorivus-transformed human embryo lung cells following in vitro cultivation. Diverse alterations in biological properties of CMV-transformed cell lines were observed during prolonged in vitro cultivation. In the CMV-Mj-HEL-2 parent line there was a gradual decrease in the number of cells expressing CMV-related antigens; at the same time, an increase in oncogenicity was observed. One tumour line, designated CMV-Mj-HEL-2,T-1, however, retained the original ratio of cells expressing CMV-related antigens for over 100 in vitro passages. The cells lost their original moderate oncogenicity during this period. A later increase in the ratio of cells without CMV antigenic markers was accompanied by the return of moderate tumorigenicity and karyotypic changes. Both cell lines were studied to determine sensitivity to superinfection with herpesviruses, induction of immune response in nude mice, and release of infectious virus."}
{"id": "PMID:221383", "title": "Induction of cellular DNA synthesis by defective human cytomegalovirus.", "content": "The results presented in this paper show that virus stocks enriched for defective particles are more effective in stimulating cellular DNA synthesis than are stocks relatively free of defective particles. Several lines of evidence support this conclusion: (1) Low levels of UV irradiation enhance the ability of standard virus stocks to stimulate cellular DNA synthesis. (2) Three different stocks derived from individual plaques (which presumably contain very few defective particles) and passaged only twice at low multiplicity, were found to be poor inducers of cellular DNA synthesis. (3) Stocks of virions obtained after serial undiluted passage which were shown to be enriched for defective particles were quite effective in stimulating cellular DNA synthesis.", "contents": "Induction of cellular DNA synthesis by defective human cytomegalovirus. The results presented in this paper show that virus stocks enriched for defective particles are more effective in stimulating cellular DNA synthesis than are stocks relatively free of defective particles. Several lines of evidence support this conclusion: (1) Low levels of UV irradiation enhance the ability of standard virus stocks to stimulate cellular DNA synthesis. (2) Three different stocks derived from individual plaques (which presumably contain very few defective particles) and passaged only twice at low multiplicity, were found to be poor inducers of cellular DNA synthesis. (3) Stocks of virions obtained after serial undiluted passage which were shown to be enriched for defective particles were quite effective in stimulating cellular DNA synthesis."}
{"id": "PMID:221384", "title": "Pronephric tumour cell lines from herpesvirus-transformed cells.", "content": "Pronephric tumor cell lines have been established from tumours induced after inoculation of embryos with herpesvirus cultivated in vitro. Neoplastic properties of the lines are characterized.", "contents": "Pronephric tumour cell lines from herpesvirus-transformed cells. Pronephric tumor cell lines have been established from tumours induced after inoculation of embryos with herpesvirus cultivated in vitro. Neoplastic properties of the lines are characterized."}
{"id": "PMID:221385", "title": "Inhibition of Epstein-Barr virus transformation: evidence for a block between EBNA production and cell proliferation.", "content": "Non-adherent lymphocyte populations prepared from donors with previous EBV infection transformed in the usual way in response to EBV. However, transformation was completely inhibited in the presence of adult but not fetal human fibroblasts. Such inhibition was associated with lymphocytes from donors with prior EBV infection, but not from those without, and there appears to be an immunological basis for inhibition. Inhibition was associated with production of EBNA and was reversible. Addition of adult fibroblasts to non-adherent lymphocytes up to 2-4 days after infection with EBV also resulted in inhibition of transformation. These results are interpreted as indicating that EBV transformation involves two recognizable phases, with an immunological block between EBNA production and cell proliferation.", "contents": "Inhibition of Epstein-Barr virus transformation: evidence for a block between EBNA production and cell proliferation. Non-adherent lymphocyte populations prepared from donors with previous EBV infection transformed in the usual way in response to EBV. However, transformation was completely inhibited in the presence of adult but not fetal human fibroblasts. Such inhibition was associated with lymphocytes from donors with prior EBV infection, but not from those without, and there appears to be an immunological basis for inhibition. Inhibition was associated with production of EBNA and was reversible. Addition of adult fibroblasts to non-adherent lymphocytes up to 2-4 days after infection with EBV also resulted in inhibition of transformation. These results are interpreted as indicating that EBV transformation involves two recognizable phases, with an immunological block between EBNA production and cell proliferation."}
{"id": "PMID:221386", "title": "Suppression of in vitro Epstein-Barr virus infection: a new role for adult human T-lymphocytes.", "content": "In vitro EBV infection of lymphocytes from different sources indicated that B-cells of adult peripheral or fetal cord blood transform with equal efficiency whether assayed by DNA synthesis induction or immortalization. Unfractionated adult lymphocytes transformed much less efficiently than those from fetal cord blood. This effect was due to the suppression of B-cell proliferation by adult T-lymphocytes.", "contents": "Suppression of in vitro Epstein-Barr virus infection: a new role for adult human T-lymphocytes. In vitro EBV infection of lymphocytes from different sources indicated that B-cells of adult peripheral or fetal cord blood transform with equal efficiency whether assayed by DNA synthesis induction or immortalization. Unfractionated adult lymphocytes transformed much less efficiently than those from fetal cord blood. This effect was due to the suppression of B-cell proliferation by adult T-lymphocytes."}
{"id": "PMID:221387", "title": "Transfection studies in vitro and in vivo with isolated Marek's disease virus DNA.", "content": "For tranfection studies in vitro and in vivo, infectious Marek's disease virus (MDV) DNA was isolated from purified virus particles. Its sedimentation coefficient in neutral sucrose gradients was found to be 53 +/- 2S and the buoyant density in caesium chloride corresponded to 1.707 g/cm3. The virus DNA was also analysed by using the restriction endonucleases EcoRI and HindIII. High molecular-weight MDV DNA precipitated by the calcium phosphate technique was shown to be infectious in cultivated chicken embryo fibroblasts and newly hatched antibody-free chickens. Three out of eight chickens which each received between 0.5 and 2 micrograms MDV DNA by the intraabdominal route produced precipitating A-antigens in the feather follicles and/or lymphoroliferative tumours in the visceral organs. Infectious MDV was also detected in spleen and blood lymphocytes. Transformation experiemnts in vitro performed with isolated thymus cells, however, have so far produced negative results. The induction of Marek's disease and tumours by purified MDV DNA also indicates that the presence of contaminating avian oncornaviruses in the inoculum is not a necessary condition for the initiation of an MDV infection.", "contents": "Transfection studies in vitro and in vivo with isolated Marek's disease virus DNA. For tranfection studies in vitro and in vivo, infectious Marek's disease virus (MDV) DNA was isolated from purified virus particles. Its sedimentation coefficient in neutral sucrose gradients was found to be 53 +/- 2S and the buoyant density in caesium chloride corresponded to 1.707 g/cm3. The virus DNA was also analysed by using the restriction endonucleases EcoRI and HindIII. High molecular-weight MDV DNA precipitated by the calcium phosphate technique was shown to be infectious in cultivated chicken embryo fibroblasts and newly hatched antibody-free chickens. Three out of eight chickens which each received between 0.5 and 2 micrograms MDV DNA by the intraabdominal route produced precipitating A-antigens in the feather follicles and/or lymphoroliferative tumours in the visceral organs. Infectious MDV was also detected in spleen and blood lymphocytes. Transformation experiemnts in vitro performed with isolated thymus cells, however, have so far produced negative results. The induction of Marek's disease and tumours by purified MDV DNA also indicates that the presence of contaminating avian oncornaviruses in the inoculum is not a necessary condition for the initiation of an MDV infection."}
{"id": "PMID:221388", "title": "Expression of Marek's disease virus in producer and non-producer lymphoblastoid cell lines.", "content": "Continuous in vitro propagation of a producer Marek's disease (MD) lymphoblastoid cell line reduced the number of cells producing virus antigens and the inducibility of these antigens to 5-iododeoxyuridine (IUDR) but did not change the oncogenicity of the cells for chickens. In contrast, propagation of a non-producer MD cell line did not change the non-productivity of the cell line, but decreased the transplantability of the cells. The MD lines were free of replicating avian leukosis sarcoma viruses (LSV) and were susceptible to infection with LSV of subgroup A.", "contents": "Expression of Marek's disease virus in producer and non-producer lymphoblastoid cell lines. Continuous in vitro propagation of a producer Marek's disease (MD) lymphoblastoid cell line reduced the number of cells producing virus antigens and the inducibility of these antigens to 5-iododeoxyuridine (IUDR) but did not change the oncogenicity of the cells for chickens. In contrast, propagation of a non-producer MD cell line did not change the non-productivity of the cell line, but decreased the transplantability of the cells. The MD lines were free of replicating avian leukosis sarcoma viruses (LSV) and were susceptible to infection with LSV of subgroup A."}
{"id": "PMID:221389", "title": "Surface glycoprotein patterns of human haematopoietic cell lines.", "content": "Human EBV-positive and EBV-negative haematopoietic cell lines were shown to have different and easily distinguishable surface glycoprotein patterns as demonstrated using surface labelling by the galactose oxidase-tritiated sodium borohydride method.", "contents": "Surface glycoprotein patterns of human haematopoietic cell lines. Human EBV-positive and EBV-negative haematopoietic cell lines were shown to have different and easily distinguishable surface glycoprotein patterns as demonstrated using surface labelling by the galactose oxidase-tritiated sodium borohydride method."}
{"id": "PMID:221393", "title": "Antibody-dependent autologous lymphocyte cytotoxicity against cells freshly transformed by Epstein-Barr virus.", "content": "Cytotoxicity against lymphocytes freshly transformed by EBV was studied in an autologous system by trypan blue exclusion of EBNA-positive cells and 51Cr-release assay. When EBV-tranformed lymphocytes were incubated with EBV-positive serum and autologous unfractionated lymphocytes or K-cells from sero-positive healthy donors, the transformed cells were significantly damaged. The cytotoxicity against newly produced EBNA-positive lymphocytes was also remarkable when sero-positive healthy donor lymphocytes were exposed to EBV, immediately followed by incubation with positive serum. In contrast, EBV-transformed cells incubated with autologous lymphocytes or T-cells alone were not significantly affected. EBV-positive serum alone was also not cytotoxic, regardless of inactivation. These results strongly suggest that antibody-dependent cellular cytotoxicity (ADCC) plays an important role in immunological defence against EBV oncogenesis in healthy humans. However, ADCC was not seen when immunosuppressed patients were examined.", "contents": "Antibody-dependent autologous lymphocyte cytotoxicity against cells freshly transformed by Epstein-Barr virus. Cytotoxicity against lymphocytes freshly transformed by EBV was studied in an autologous system by trypan blue exclusion of EBNA-positive cells and 51Cr-release assay. When EBV-tranformed lymphocytes were incubated with EBV-positive serum and autologous unfractionated lymphocytes or K-cells from sero-positive healthy donors, the transformed cells were significantly damaged. The cytotoxicity against newly produced EBNA-positive lymphocytes was also remarkable when sero-positive healthy donor lymphocytes were exposed to EBV, immediately followed by incubation with positive serum. In contrast, EBV-transformed cells incubated with autologous lymphocytes or T-cells alone were not significantly affected. EBV-positive serum alone was also not cytotoxic, regardless of inactivation. These results strongly suggest that antibody-dependent cellular cytotoxicity (ADCC) plays an important role in immunological defence against EBV oncogenesis in healthy humans. However, ADCC was not seen when immunosuppressed patients were examined."}
{"id": "PMID:221395", "title": "Detection of Epstein-Barr virus-coded antigens in lymphocytes isolated from defined patient samples.", "content": "A preliminary report on the use of specific rabbit antisera raised to Epstein-Barr virus-coded antigens (EBNA and EA) for detection of these antigens in vivo is presented. Human lymphocytes were isolated on isokinetic gradients and the C3 receptor-bearing B-lymphocyte subpopulation was isolated, providing an enriched source of EBV-infected lymphocytes. Such technology was employed to establish the status of the EBV host-cell complex in recurrent exudative tonsillitis (RET), infectious mononucleosis (IM), and Hodgkin's and non-Hodgkin's lymphoma patients. Only EBNA was detected in the lymphocytes from the tonsils of RET patients and the peripheral blood of IM patients. However, the spleen and lymph-nodes of patients with lymphomas had lymphocytes synthesizing EBNA and EA.", "contents": "Detection of Epstein-Barr virus-coded antigens in lymphocytes isolated from defined patient samples. A preliminary report on the use of specific rabbit antisera raised to Epstein-Barr virus-coded antigens (EBNA and EA) for detection of these antigens in vivo is presented. Human lymphocytes were isolated on isokinetic gradients and the C3 receptor-bearing B-lymphocyte subpopulation was isolated, providing an enriched source of EBV-infected lymphocytes. Such technology was employed to establish the status of the EBV host-cell complex in recurrent exudative tonsillitis (RET), infectious mononucleosis (IM), and Hodgkin's and non-Hodgkin's lymphoma patients. Only EBNA was detected in the lymphocytes from the tonsils of RET patients and the peripheral blood of IM patients. However, the spleen and lymph-nodes of patients with lymphomas had lymphocytes synthesizing EBNA and EA."}
{"id": "PMID:221397", "title": "Replication of Epstein-Barr virus DNA in epithelial cells in vivo.", "content": "Epstein-Barr virus (EBV)-specific complementary RNA (cRNA) was hybridized in situ to oropharyngeal epithelial cells taken from patients with infectious mononucleosis. Cells from patients shedding virus in the throat hybridized signifnicant quantities of cRNA, whereas cells from EBV-negative sources did not. The degree of hybridization indicated a large EBV genome number per infected epithelial cell and suggested that these cells were the source of virus found in the throat. This finding may explain the presence of the EBV genome in the malignant epithelial cells of nasopharyngeal carcinoma.", "contents": "Replication of Epstein-Barr virus DNA in epithelial cells in vivo. Epstein-Barr virus (EBV)-specific complementary RNA (cRNA) was hybridized in situ to oropharyngeal epithelial cells taken from patients with infectious mononucleosis. Cells from patients shedding virus in the throat hybridized signifnicant quantities of cRNA, whereas cells from EBV-negative sources did not. The degree of hybridization indicated a large EBV genome number per infected epithelial cell and suggested that these cells were the source of virus found in the throat. This finding may explain the presence of the EBV genome in the malignant epithelial cells of nasopharyngeal carcinoma."}
{"id": "PMID:221398", "title": "Lymphocyte transformation and interferon production as measures of cellular immunity in lymphoma patients.", "content": "Our studies of in vitro cellular immune responses to herpesviruses have shown that, before treatment, lymphoma patients have decreased transformation to varicella-zoster virus antigen compared to herpes simplex virus and cytomegalovirus antigens. Interferon production to varicella-zoster virus and cytomegalovirus antigens is also decreased. During the first six months of treatment, decreased lymphocyte transformation and interferon production to all herpesviral antigens was observed. Among patients in long-term remission, recovery from the suppression associated with treatment was noted except that interferon production to varicella-zoster virus antigen remained decreased.", "contents": "Lymphocyte transformation and interferon production as measures of cellular immunity in lymphoma patients. Our studies of in vitro cellular immune responses to herpesviruses have shown that, before treatment, lymphoma patients have decreased transformation to varicella-zoster virus antigen compared to herpes simplex virus and cytomegalovirus antigens. Interferon production to varicella-zoster virus and cytomegalovirus antigens is also decreased. During the first six months of treatment, decreased lymphocyte transformation and interferon production to all herpesviral antigens was observed. Among patients in long-term remission, recovery from the suppression associated with treatment was noted except that interferon production to varicella-zoster virus antigen remained decreased."}
{"id": "PMID:221399", "title": "Sequential changes in cell-mediated immune responses to herpes simplex virus following primary herpetic infection in man.", "content": "During primary herpes simlex virus infections, sensitization to the virus was demonstrated at the time of presentation by lymphocyte blastogenesis. Recovery from infection coincided with development of the macrophage migration inhibition response, and it is suggested that macrophage activation by products of stimulated lymphocytes contributes to control of the infection.", "contents": "Sequential changes in cell-mediated immune responses to herpes simplex virus following primary herpetic infection in man. During primary herpes simlex virus infections, sensitization to the virus was demonstrated at the time of presentation by lymphocyte blastogenesis. Recovery from infection coincided with development of the macrophage migration inhibition response, and it is suggested that macrophage activation by products of stimulated lymphocytes contributes to control of the infection."}
{"id": "PMID:221400", "title": "Immune responses to vaginal or systemic infection of mice with herpes simplex virus type 2.", "content": "Relationships among cell-mediated immune (CMI) responses, neutralizing antibody, and macrophages in host resistance to vaginal or systemic infection with HSV-2 were defined in BALB/c mice. The importance of T-lymphocytes in resistance to either systemic or vaginal infection was demonstrated by increased susceptibility of mice depleted of T-lymphocytes. A role for non-specific resistance against the systemic, but not vaginal, infection was demonstrated by increased susceptibility of mice depleted of macrophages. The temporal relationships among the serum antibody response, and the delayed-type hypersensitivity (DTH) and splenic proliferative CMI responses were defined in individual animals. Vaginal infection was associated exclusively with relatively transient CMI responses which appeared during the acute infection. After systemic infection, CMI responses appeared during the acute infection. After systemic infection, CMI responses appeared during the acute infection and persisted for approximately five weeks, while a humoral response appeared in surviving animals and persisted for at least four months. The results suggest that CMI is the predominant host response to vaginal HSV-2 infection, while both CMI and macrophage-mediated antiviral activity may be involved in recovery from primary systemic infection with HSV-2.", "contents": "Immune responses to vaginal or systemic infection of mice with herpes simplex virus type 2. Relationships among cell-mediated immune (CMI) responses, neutralizing antibody, and macrophages in host resistance to vaginal or systemic infection with HSV-2 were defined in BALB/c mice. The importance of T-lymphocytes in resistance to either systemic or vaginal infection was demonstrated by increased susceptibility of mice depleted of T-lymphocytes. A role for non-specific resistance against the systemic, but not vaginal, infection was demonstrated by increased susceptibility of mice depleted of macrophages. The temporal relationships among the serum antibody response, and the delayed-type hypersensitivity (DTH) and splenic proliferative CMI responses were defined in individual animals. Vaginal infection was associated exclusively with relatively transient CMI responses which appeared during the acute infection. After systemic infection, CMI responses appeared during the acute infection. After systemic infection, CMI responses appeared during the acute infection and persisted for approximately five weeks, while a humoral response appeared in surviving animals and persisted for at least four months. The results suggest that CMI is the predominant host response to vaginal HSV-2 infection, while both CMI and macrophage-mediated antiviral activity may be involved in recovery from primary systemic infection with HSV-2."}
{"id": "PMID:221401", "title": "Herpes simplex virus latency in patients with multiple sclerosis, lymphoma and normal humans.", "content": "Herpes simplex virus (HSV) was isolated from the trigeminal ganglia (TG) of 12 cadavers (10 traumatic deaths, one lymphoma and one multiple sclerosis). The cadaver with multiple sclerosis showed large bilateral trigeminal nerve root entry zone areas of demyelination. It is hypothesized that HSV is capable of migrating to the trigeminal nerve root entry zone and initiating demyelinating disease.", "contents": "Herpes simplex virus latency in patients with multiple sclerosis, lymphoma and normal humans. Herpes simplex virus (HSV) was isolated from the trigeminal ganglia (TG) of 12 cadavers (10 traumatic deaths, one lymphoma and one multiple sclerosis). The cadaver with multiple sclerosis showed large bilateral trigeminal nerve root entry zone areas of demyelination. It is hypothesized that HSV is capable of migrating to the trigeminal nerve root entry zone and initiating demyelinating disease."}
{"id": "PMID:221402", "title": "Immunosuppression reactivates and disseminates latent murine cytomegalovirus.", "content": "When searched for by standard virological methods, murine cytomegalovirus (MCMV) becomes undetectable by four months after inoculation of mice. However, a two-week regimen of immunosuppression with antilymphocyte serum and corticosteroid results in reactivation and dissemination of the virus in virtually all animals. This system should be useful in defining the pathogenesis of generalized cytomegalic disease resulting from reactivation of latent virus in immunocompromized individuals.", "contents": "Immunosuppression reactivates and disseminates latent murine cytomegalovirus. When searched for by standard virological methods, murine cytomegalovirus (MCMV) becomes undetectable by four months after inoculation of mice. However, a two-week regimen of immunosuppression with antilymphocyte serum and corticosteroid results in reactivation and dissemination of the virus in virtually all animals. This system should be useful in defining the pathogenesis of generalized cytomegalic disease resulting from reactivation of latent virus in immunocompromized individuals."}
{"id": "PMID:221403", "title": "Differences in susceptibility to herpes simplex virus infection of inbred strains of mice.", "content": "Marked differences were observed between the susceptibility of adult C57BL/6 and DBA/2 mice to infection with HSV-1. These differences were seen after various infection schedules but were most marked after i.p. infection. A significant difference between the LD50 after i.p. infection was also observed between LPS-resistant C3H/HeJ and the closely related LPS-sensitive C3HeB/FeJ mice. Injection of LPS significantly increased the LD50 after i.p. infection with HSV in C57BL/6 or C3H/HeJ mice but not in C3HeB/FeJ mice. In vitro pretreatment with LPS was necessary to demonstrate replication of HSV in mouse spleen-cell cultures. Such replication could be demonstrated in cultures of DBA/2 and C3HeB/FeJ but not in C57BL/6 or C3H/HeJ mice.", "contents": "Differences in susceptibility to herpes simplex virus infection of inbred strains of mice. Marked differences were observed between the susceptibility of adult C57BL/6 and DBA/2 mice to infection with HSV-1. These differences were seen after various infection schedules but were most marked after i.p. infection. A significant difference between the LD50 after i.p. infection was also observed between LPS-resistant C3H/HeJ and the closely related LPS-sensitive C3HeB/FeJ mice. Injection of LPS significantly increased the LD50 after i.p. infection with HSV in C57BL/6 or C3H/HeJ mice but not in C3HeB/FeJ mice. In vitro pretreatment with LPS was necessary to demonstrate replication of HSV in mouse spleen-cell cultures. Such replication could be demonstrated in cultures of DBA/2 and C3HeB/FeJ but not in C57BL/6 or C3H/HeJ mice."}
{"id": "PMID:221416", "title": "Vaccination against diseases associated with herpesvirus infections in animals: a review.", "content": "An account is presented of the development and use of herpesvirus vaccines in domestic animals, with particular reference to those viruses causing cytolytic rather than oncogenic infections. The chief infections covered are Aujeszky's disease (AD or pseudorabies), infectious bovine rhinotracheitis (IBR) and equine rhinopneumonitis (equine abortion; EHV-1). Others mentioned are feline viral rhinotracheitis and malignant catarrhal fever of cattle. Both live-modified and inactivated vaccines are widely used or under development for ADV, IBR and EHV-1. Live vaccines are generally regarded as successful in some circumstances but have major drawbacks, both in regard to safety or immunogenicity for the individual animal or to efforts to control and eliminate the viruses from whole populations. Difficulties remian in the preparation and use of inactivated vaccines, which still suffer from many of the epidemiological objections raised against modified live vaccines.", "contents": "Vaccination against diseases associated with herpesvirus infections in animals: a review. An account is presented of the development and use of herpesvirus vaccines in domestic animals, with particular reference to those viruses causing cytolytic rather than oncogenic infections. The chief infections covered are Aujeszky's disease (AD or pseudorabies), infectious bovine rhinotracheitis (IBR) and equine rhinopneumonitis (equine abortion; EHV-1). Others mentioned are feline viral rhinotracheitis and malignant catarrhal fever of cattle. Both live-modified and inactivated vaccines are widely used or under development for ADV, IBR and EHV-1. Live vaccines are generally regarded as successful in some circumstances but have major drawbacks, both in regard to safety or immunogenicity for the individual animal or to efforts to control and eliminate the viruses from whole populations. Difficulties remian in the preparation and use of inactivated vaccines, which still suffer from many of the epidemiological objections raised against modified live vaccines."}
{"id": "PMID:221417", "title": "The interaction between herpesvirus and oncornavirus of guineapigs: in vitro and in vivo studies.", "content": "In vitro, cultured guineapig doubly infected with both guineapig herpesvirus (GPHLV) and guineapig oncornavirus (GPOV) revealed pseudotype virus particles with oncornavirus morphology coated with GPHLV antigen as detected by immunoferritin electron microscopy. In vivo, infection of Hartley guineapigs with both GPHLV and GPOV induced hyperplasia in lymph-nodes in a higher percentage of animals than in those that received only one virus type. In addition, experimental GPHLV infection of strain 2 guineapigs caused some delay in the development of L2C leukaemia in inoculated animals.", "contents": "The interaction between herpesvirus and oncornavirus of guineapigs: in vitro and in vivo studies. In vitro, cultured guineapig doubly infected with both guineapig herpesvirus (GPHLV) and guineapig oncornavirus (GPOV) revealed pseudotype virus particles with oncornavirus morphology coated with GPHLV antigen as detected by immunoferritin electron microscopy. In vivo, infection of Hartley guineapigs with both GPHLV and GPOV induced hyperplasia in lymph-nodes in a higher percentage of animals than in those that received only one virus type. In addition, experimental GPHLV infection of strain 2 guineapigs caused some delay in the development of L2C leukaemia in inoculated animals."}
{"id": "PMID:221418", "title": "Effect of ara-T on the replication of herpes simplex virus, varicella-zoster virus and cytomegalovirus.", "content": "The thymidine analogue, 1-beta-arabinofuranosylthymine (ara-T), has previously been found to selectively inhibit herpes simplex virus (HSV) replication. At a relatively non-toxic concentration (50 microgram/ml), ara-T reduced HSV yields by a factor of 10,000-100,000. Ara-T was also effective in inhibiting the replication of variecella-zoster virus (VZV) in vitro in human embryo fibroblasts, completely preventing VZV-specific cytopathic effects (CPE). Ara-T reduced the cell-free virus and plaque-forming cell (PFC) yields of VZV as well as of the simian varicella-like virus, Delta herpesvirus. In contrast to HSV and VZV, cytomegalovirus (CMV) replication was relatively resistant to ara-T. Neither CPE nor the incorporation of 3H-thymidine into acid-insoluble material in CMV-infected cells was markedly affected. Interpretation of these results with regard to virus-induced deoxypyrimidine kinase is discussed.", "contents": "Effect of ara-T on the replication of herpes simplex virus, varicella-zoster virus and cytomegalovirus. The thymidine analogue, 1-beta-arabinofuranosylthymine (ara-T), has previously been found to selectively inhibit herpes simplex virus (HSV) replication. At a relatively non-toxic concentration (50 microgram/ml), ara-T reduced HSV yields by a factor of 10,000-100,000. Ara-T was also effective in inhibiting the replication of variecella-zoster virus (VZV) in vitro in human embryo fibroblasts, completely preventing VZV-specific cytopathic effects (CPE). Ara-T reduced the cell-free virus and plaque-forming cell (PFC) yields of VZV as well as of the simian varicella-like virus, Delta herpesvirus. In contrast to HSV and VZV, cytomegalovirus (CMV) replication was relatively resistant to ara-T. Neither CPE nor the incorporation of 3H-thymidine into acid-insoluble material in CMV-infected cells was markedly affected. Interpretation of these results with regard to virus-induced deoxypyrimidine kinase is discussed."}
{"id": "PMID:221423", "title": "Effects of theophylline on capillary tube leucocyte migration.", "content": "Theophylline stimulates the capillary tube migration of human peripheral blood mixed leucocytes. Minor stimulation of polymorph migration is produced directly by theophylline and dibutyryl cyclic AMP, but polymorph migration is markedly stimulated by mononuclear leucocyte culture supernatants to which theophylline has been added. These results suggest that polymorph migration is stimulated when intracellular cyclic AMP increases, and that mononuclear leucocytes produce a potential migration stimulator whose activity is enhanced by theophylline.", "contents": "Effects of theophylline on capillary tube leucocyte migration. Theophylline stimulates the capillary tube migration of human peripheral blood mixed leucocytes. Minor stimulation of polymorph migration is produced directly by theophylline and dibutyryl cyclic AMP, but polymorph migration is markedly stimulated by mononuclear leucocyte culture supernatants to which theophylline has been added. These results suggest that polymorph migration is stimulated when intracellular cyclic AMP increases, and that mononuclear leucocytes produce a potential migration stimulator whose activity is enhanced by theophylline."}
{"id": "PMID:221424", "title": "Rhesus monkey (macaca mulatta) allotypes. Identification of three low density lipoprotein allotypes controlled by independent genes.", "content": "Three rhesus monkey allotypes are described, which are located on distinct low density lipoprotein molecules. These three markers have been detected using double immunodiffusion in agar. They are inherited in a simple Mendelian manner and controlled by three independent genes.", "contents": "Rhesus monkey (macaca mulatta) allotypes. Identification of three low density lipoprotein allotypes controlled by independent genes. Three rhesus monkey allotypes are described, which are located on distinct low density lipoprotein molecules. These three markers have been detected using double immunodiffusion in agar. They are inherited in a simple Mendelian manner and controlled by three independent genes."}
{"id": "PMID:221425", "title": "Further studies on the adjuvant effect of silica on IgE antibody production in mice.", "content": "The effects of amorphous silica (Aerosil) and of aluminium hydroxide on anti-DNP IgE antibody production were studied in Swiss mice preimmunized with Ascaris protein and then challenged 7 days later with DNP-ASC. Aerosil exerted an adjuvant effect especially when it was injected together with the DNP-ASC conjugate. Al(OH)3 had a weaker adjuvant effect than that produced by Aerosil and then only when it was injected with the DNP-ASC conjugate. Al(OH)3 given with Ascaris extract 7 days before complete antigen had an inhibitory effect on the anti-DNP IgE antibody production.", "contents": "Further studies on the adjuvant effect of silica on IgE antibody production in mice. The effects of amorphous silica (Aerosil) and of aluminium hydroxide on anti-DNP IgE antibody production were studied in Swiss mice preimmunized with Ascaris protein and then challenged 7 days later with DNP-ASC. Aerosil exerted an adjuvant effect especially when it was injected together with the DNP-ASC conjugate. Al(OH)3 had a weaker adjuvant effect than that produced by Aerosil and then only when it was injected with the DNP-ASC conjugate. Al(OH)3 given with Ascaris extract 7 days before complete antigen had an inhibitory effect on the anti-DNP IgE antibody production."}
{"id": "PMID:221426", "title": "Detection of a microsomal antigen and its antibody in human liver diseases.", "content": "Sera of 173 patients with various forms of liver disease along with serum precipitates produced by polyethylene glycol were screened for the presence of a microsomal antigen referred to as ubiquitous tissue antigen (UTA) and its antibody by double diffusion precipitation in agarose gel. UTA was detected in 7 or 26 patients with chronic active hepatitis, 1 of 5 with alcoholic hepatitis, 2 of 14 with alcoholic cirrhosis and 18 of 98 with hepatoma. Antibodies to UTA were found only in 2 patients with chronic active hepatitis, 1 with alcoholic cirrhosis and 1 with hepatoma. No UTA or its antibody were noted in sera of 5 patients with alcoholic fatty liver, 10 patients with hepatitis B, and 15 asymptomatic carriers of HBsAg. Positivity for the UTA or its antibody was restricted to severe, chronic cases irrespective of diagnosis, indicating that persistent tissue destruction might be necessary for antigen release or antibody formation.", "contents": "Detection of a microsomal antigen and its antibody in human liver diseases. Sera of 173 patients with various forms of liver disease along with serum precipitates produced by polyethylene glycol were screened for the presence of a microsomal antigen referred to as ubiquitous tissue antigen (UTA) and its antibody by double diffusion precipitation in agarose gel. UTA was detected in 7 or 26 patients with chronic active hepatitis, 1 of 5 with alcoholic hepatitis, 2 of 14 with alcoholic cirrhosis and 18 of 98 with hepatoma. Antibodies to UTA were found only in 2 patients with chronic active hepatitis, 1 with alcoholic cirrhosis and 1 with hepatoma. No UTA or its antibody were noted in sera of 5 patients with alcoholic fatty liver, 10 patients with hepatitis B, and 15 asymptomatic carriers of HBsAg. Positivity for the UTA or its antibody was restricted to severe, chronic cases irrespective of diagnosis, indicating that persistent tissue destruction might be necessary for antigen release or antibody formation."}
{"id": "PMID:221428", "title": "Fluorescence study of thymus lymphocytes of X-irradiated mice and their progeny.", "content": "The mechanisms of changes in the ultra-violet fluorescence (U.V.F.) intensity of mouse thymus lymphocytes 24 hours and 30 days after whole-body X-irradiation have been studied. The thymus lymphocytes of the first generation offspring (F1) from X-irradiated males and unirradiated females were also investigated. At 24 hours after irradiation the U.V.F. intensity decreased for small doses (50 and 65 rad) and increased for doses of more than 100 rad. The changes in U.V.F. intensity were related to a size-independent mechanism. It was found that the U.V.F. increase for doses of 100-700 rad was not connected with the appearance of non-viable (eosin test) cells. The changes in U.V.F. intensity and cellular composition of the thymus were the same 30 days after irradiation and for F1 mice. The increase in U.V.F. intensity was about 14% and did not depend on dose between 50 and 500 rad. About one-half of this increase was connected with an increase in the proportion of medium and large lymphocytes in the thymus. The rest of the effect was related to a size-independent mechanism.", "contents": "Fluorescence study of thymus lymphocytes of X-irradiated mice and their progeny. The mechanisms of changes in the ultra-violet fluorescence (U.V.F.) intensity of mouse thymus lymphocytes 24 hours and 30 days after whole-body X-irradiation have been studied. The thymus lymphocytes of the first generation offspring (F1) from X-irradiated males and unirradiated females were also investigated. At 24 hours after irradiation the U.V.F. intensity decreased for small doses (50 and 65 rad) and increased for doses of more than 100 rad. The changes in U.V.F. intensity were related to a size-independent mechanism. It was found that the U.V.F. increase for doses of 100-700 rad was not connected with the appearance of non-viable (eosin test) cells. The changes in U.V.F. intensity and cellular composition of the thymus were the same 30 days after irradiation and for F1 mice. The increase in U.V.F. intensity was about 14% and did not depend on dose between 50 and 500 rad. About one-half of this increase was connected with an increase in the proportion of medium and large lymphocytes in the thymus. The rest of the effect was related to a size-independent mechanism."}
{"id": "PMID:221430", "title": "The formation and reaction of methyl radicals produced by direct photolysis of aqueous solutions of N-acetyl substituted aliphatic amino acids at 77K.", "content": "Photolysis of amino acids, peptides and their derivatives leads to the formation of free radicals in these substances. The electron-spin-resonance spectra obtained directly after irradiation at 77 K are not very well resolved.  They are recognizable as the superposition of the spectra of different types of photoproduced radicals. CH3 radicals are formed by U.V. irradiation if methyl groups are present in the molecule. These radicals are easily detectable because of their four line spectrum. In this paper the formation of methyl radicals and their reaction with undamaged molecules of N-acetyl-substituted amino acids in investigated. The number of CH3 radicals present after a 30 min U.V. irradiation is higher if preceding U.V. irradiations and heat treatments are performed. The overall concentration of radicals is reduced only partially during this heat-treatment, while the CH3 radicals decay completely. Other experiments show that the rate of and the yield of CH3 radicals by U.V. irradiation increase with the dose of a preceding gamma-irradiation. The results suggest that there are substances present which are responsible for the higher production rate of methyl radicals after a preceding treatment. It is assumed that radicals are precursors of the fast-formed CH3 radicals", "contents": "The formation and reaction of methyl radicals produced by direct photolysis of aqueous solutions of N-acetyl substituted aliphatic amino acids at 77K. Photolysis of amino acids, peptides and their derivatives leads to the formation of free radicals in these substances. The electron-spin-resonance spectra obtained directly after irradiation at 77 K are not very well resolved.  They are recognizable as the superposition of the spectra of different types of photoproduced radicals. CH3 radicals are formed by U.V. irradiation if methyl groups are present in the molecule. These radicals are easily detectable because of their four line spectrum. In this paper the formation of methyl radicals and their reaction with undamaged molecules of N-acetyl-substituted amino acids in investigated. The number of CH3 radicals present after a 30 min U.V. irradiation is higher if preceding U.V. irradiations and heat treatments are performed. The overall concentration of radicals is reduced only partially during this heat-treatment, while the CH3 radicals decay completely. Other experiments show that the rate of and the yield of CH3 radicals by U.V. irradiation increase with the dose of a preceding gamma-irradiation. The results suggest that there are substances present which are responsible for the higher production rate of methyl radicals after a preceding treatment. It is assumed that radicals are precursors of the fast-formed CH3 radicals"}
{"id": "PMID:221432", "title": "Naturally occurring vitamin D3 in fish products analysed by HPLC, using vitamin D2 as an international standard.", "content": "A chemical method for the analysis of naturally occurring vitamin D is proposed. The unsaponifiable matter of oils and tissues is prepared, cholesterol is partly removed by double precipitation at low temperature in methanol. The vitamin D fraction is collected on an adsorption column by high performance liquid chromatography. The fraction is further purified and the vitamins D2 and D3 are separated on a partition column (reverse phase) by HPLC. Recovery was 89 to 93%, standard deviation 3%. The only vitamin D analogue found in fish oils, livers and fillets, was cholecalciferol (D3). Hence, ergocalciferol (D2) could be used as an internal standard. The provitamins ergosterol and 7-dehydrocholesterol, as well as the previtamins, were separated from the vitamin D-fraction on the adsorption column. Results in the range 0.050 to 134 microgram D3 per gram (2 to 5360 I.U. per gram) are given. One cod liver oil was analysed in a rat bioassay, giving supporting results.", "contents": "Naturally occurring vitamin D3 in fish products analysed by HPLC, using vitamin D2 as an international standard. A chemical method for the analysis of naturally occurring vitamin D is proposed. The unsaponifiable matter of oils and tissues is prepared, cholesterol is partly removed by double precipitation at low temperature in methanol. The vitamin D fraction is collected on an adsorption column by high performance liquid chromatography. The fraction is further purified and the vitamins D2 and D3 are separated on a partition column (reverse phase) by HPLC. Recovery was 89 to 93%, standard deviation 3%. The only vitamin D analogue found in fish oils, livers and fillets, was cholecalciferol (D3). Hence, ergocalciferol (D2) could be used as an internal standard. The provitamins ergosterol and 7-dehydrocholesterol, as well as the previtamins, were separated from the vitamin D-fraction on the adsorption column. Results in the range 0.050 to 134 microgram D3 per gram (2 to 5360 I.U. per gram) are given. One cod liver oil was analysed in a rat bioassay, giving supporting results."}
{"id": "PMID:221433", "title": "Induction of the FAD synthetase system in rat liver by phenobarbital administration.", "content": "FMN and FAD synthesizing activities in rat liver were investigated when drug metabolizing enzymes were induced by phenobarbital. The FAD content of the liver mitochondrial and microsomal fractions were increased by either one shot administration or three successive daily administrations of phenobarbital. Similarly the flavokinase and FAD pyrophosphorylase activities also increased in the mitochondrial, microsomal and cytosol fractions. The authors have verified that activation of the FAD synthesizing system is induced by phenobarbital and suggest that the FMN and FAD contents are regulated not only by variations of flavin enzyme apoprotein, but also by changes in flavokinase and FAD pyrophosphorylase activities.", "contents": "Induction of the FAD synthetase system in rat liver by phenobarbital administration. FMN and FAD synthesizing activities in rat liver were investigated when drug metabolizing enzymes were induced by phenobarbital. The FAD content of the liver mitochondrial and microsomal fractions were increased by either one shot administration or three successive daily administrations of phenobarbital. Similarly the flavokinase and FAD pyrophosphorylase activities also increased in the mitochondrial, microsomal and cytosol fractions. The authors have verified that activation of the FAD synthesizing system is induced by phenobarbital and suggest that the FMN and FAD contents are regulated not only by variations of flavin enzyme apoprotein, but also by changes in flavokinase and FAD pyrophosphorylase activities."}
{"id": "PMID:221435", "title": "Collagenase from corneal cell cultures and its modulation by phagocytosis.", "content": "The uptake of latex by fibroblasts in confluent primary culture results in the secretion of collagenase at a linear rate for a prolonged period. Phagocytosis might therefore constitute an important level of collagenase regulation in corneal ulceration. The collagenase in cell cultures is present in a latent form (40,000 MW) like that obtained from organ cultures of ulcerating corneas and can be activated proteolytically. Production of the latent collagenase in cell culture depends upon the presence of serum and diminishes greatly when serum is removed from the medium. Collagenase activity can be demonstrated after the latent collagenase has been separated from serum antiproteases in the media. Alternatively, careful titration of the crude media with trypsin to saturate serum antiproteases, to release collagenase from the complex with alpha 2-macroglobulin, and to activate latent collagenase also results in measurable collagenase activity. The collagenase that is secreted cleaves fibrillar type I collagen and cleaves soluble type I collagen into the typical 3/4 and 1/4 length fragments, as demonstrated by SDS-gel electrophoresis and electron microscopy.", "contents": "Collagenase from corneal cell cultures and its modulation by phagocytosis. The uptake of latex by fibroblasts in confluent primary culture results in the secretion of collagenase at a linear rate for a prolonged period. Phagocytosis might therefore constitute an important level of collagenase regulation in corneal ulceration. The collagenase in cell cultures is present in a latent form (40,000 MW) like that obtained from organ cultures of ulcerating corneas and can be activated proteolytically. Production of the latent collagenase in cell culture depends upon the presence of serum and diminishes greatly when serum is removed from the medium. Collagenase activity can be demonstrated after the latent collagenase has been separated from serum antiproteases in the media. Alternatively, careful titration of the crude media with trypsin to saturate serum antiproteases, to release collagenase from the complex with alpha 2-macroglobulin, and to activate latent collagenase also results in measurable collagenase activity. The collagenase that is secreted cleaves fibrillar type I collagen and cleaves soluble type I collagen into the typical 3/4 and 1/4 length fragments, as demonstrated by SDS-gel electrophoresis and electron microscopy."}
{"id": "PMID:221436", "title": "Electron paramagnetic resonance study of iron oxalate in calcium oxalate renal stones.", "content": "Weak electron paramagnetic resonance (EPR) signals from a number of calcium oxalate renal stones are attributed to an iron oxalate component. The g-value of the resonance is 2.0036 and its width is approximately 9 gauss. The EPR resonance from stones has the same characteristics as resonances from iron introduced into calcium oxalate and oxalic acid as an impurity. A sharp increase in EPR signal when calcium oxalate renal stones are exposed to intense light is attributable to the reduction of Fe3+ and the formation of the oxalate radical ion (C2O4)-.", "contents": "Electron paramagnetic resonance study of iron oxalate in calcium oxalate renal stones. Weak electron paramagnetic resonance (EPR) signals from a number of calcium oxalate renal stones are attributed to an iron oxalate component. The g-value of the resonance is 2.0036 and its width is approximately 9 gauss. The EPR resonance from stones has the same characteristics as resonances from iron introduced into calcium oxalate and oxalic acid as an impurity. A sharp increase in EPR signal when calcium oxalate renal stones are exposed to intense light is attributable to the reduction of Fe3+ and the formation of the oxalate radical ion (C2O4)-."}
{"id": "PMID:221437", "title": "Quantitative analysis of alpha and beta adrenergic receptor densities in the lower urinary tract of the dog and the rabbit.", "content": "Using specific radioligand receptor binding assays, we have, for the first time, quantitated both alpha- and beta-adrenergic receptors in the musculature of the lower ureter, bladder body, posterior bladder base, and proximal urethra of the dog, and in the bladder base and body of the rabbit. For the beta receptor assay 3H-dihydroalprenolol was used as the ligand, and, for the alpha receptor assay, 3H-dihydroergocryptine was used. In the dog, there was a significantly greater density of beta receptors in the bladder body than in either the ureter or the posterior bladder base. The urethra had an intermediate density. The bladder base and the proximal urethra had a significantly greater density of alpha receptors than either the ureter or the bladder dome. The dissociation constant of beta receptors for DHA was approximately 9 nM for all tissues studied, and that of alpha receptors for DHE approximately 7 nM. A similar distribution of alpha-and beta adrenergic receptors was seen in the rabbit bladder.", "contents": "Quantitative analysis of alpha and beta adrenergic receptor densities in the lower urinary tract of the dog and the rabbit. Using specific radioligand receptor binding assays, we have, for the first time, quantitated both alpha- and beta-adrenergic receptors in the musculature of the lower ureter, bladder body, posterior bladder base, and proximal urethra of the dog, and in the bladder base and body of the rabbit. For the beta receptor assay 3H-dihydroalprenolol was used as the ligand, and, for the alpha receptor assay, 3H-dihydroergocryptine was used. In the dog, there was a significantly greater density of beta receptors in the bladder body than in either the ureter or the posterior bladder base. The urethra had an intermediate density. The bladder base and the proximal urethra had a significantly greater density of alpha receptors than either the ureter or the bladder dome. The dissociation constant of beta receptors for DHA was approximately 9 nM for all tissues studied, and that of alpha receptors for DHE approximately 7 nM. A similar distribution of alpha-and beta adrenergic receptors was seen in the rabbit bladder."}
{"id": "PMID:221438", "title": "Etiology of infantile enteritis in South Africa.", "content": "Infantile enteritis constitutes a major health problem in developing countries. Several investigations into the etiology of this condition among various South African populations have been undertaken during the past few years. Recent studies of black urban infants have revealed that salmonellae, shigellae, enterotoxigenic Enterobacteriaceae, and rotaviruses play a relatively minor role in infantile enteritis. On the other hand, all studies, including a number performed several years ago, have demonstrated that Escherichia coli strains belonging to traditional enteropathogenic serotypes are more frequently recovered from patients with diarrhea than from matched control subjects. These bacteria are particularly prominent during the summer months at the height of the annual gastroenteritis epidemic. Recent studies have indicated the importance of Campylobacter fetus in infantile enteritis, especially in children younger than nine months. The data point to a complex multiple etiology of infantile enteritis in South Africa, which will require clarification before specific preventive measures can be instituted.", "contents": "Etiology of infantile enteritis in South Africa. Infantile enteritis constitutes a major health problem in developing countries. Several investigations into the etiology of this condition among various South African populations have been undertaken during the past few years. Recent studies of black urban infants have revealed that salmonellae, shigellae, enterotoxigenic Enterobacteriaceae, and rotaviruses play a relatively minor role in infantile enteritis. On the other hand, all studies, including a number performed several years ago, have demonstrated that Escherichia coli strains belonging to traditional enteropathogenic serotypes are more frequently recovered from patients with diarrhea than from matched control subjects. These bacteria are particularly prominent during the summer months at the height of the annual gastroenteritis epidemic. Recent studies have indicated the importance of Campylobacter fetus in infantile enteritis, especially in children younger than nine months. The data point to a complex multiple etiology of infantile enteritis in South Africa, which will require clarification before specific preventive measures can be instituted."}
{"id": "PMID:221439", "title": "Transitory hypoadrenalism due to long-term treatment with antiovulatory compounds.", "content": "A considerable number of women receiving antiovulatory compounds or estrogens complain of weakness and fatigability, suggesting a state of clinical hypoadrenalism. For this reason, levels of plasma ACTH and plasma cortisol were determined in 25 women with such complaints both during treatment and at various intervals after cessation of this treatment. The results obtained showed that there was a significant inhibition of ACTH secretion during long-term treatment with antiovulatory compounds or estrogens, and in half of the cases, there was a delay in normalization of the pituitary-adrenal axis following interruption of the drug, supporting a state of transitory hypoadrenalism.", "contents": "Transitory hypoadrenalism due to long-term treatment with antiovulatory compounds. A considerable number of women receiving antiovulatory compounds or estrogens complain of weakness and fatigability, suggesting a state of clinical hypoadrenalism. For this reason, levels of plasma ACTH and plasma cortisol were determined in 25 women with such complaints both during treatment and at various intervals after cessation of this treatment. The results obtained showed that there was a significant inhibition of ACTH secretion during long-term treatment with antiovulatory compounds or estrogens, and in half of the cases, there was a delay in normalization of the pituitary-adrenal axis following interruption of the drug, supporting a state of transitory hypoadrenalism."}
{"id": "PMID:221441", "title": "[Cutaneous cysts and cystic skin tumors].", "content": "The nomenclature and pathogenesis of cutaneous cysts is discussed along the lines of their pathological properties. On the basis of histological and experimental evidence it is concluded that most cysts represent benign neoplasms derived from pluripotential cells.", "contents": "[Cutaneous cysts and cystic skin tumors]. The nomenclature and pathogenesis of cutaneous cysts is discussed along the lines of their pathological properties. On the basis of histological and experimental evidence it is concluded that most cysts represent benign neoplasms derived from pluripotential cells."}
{"id": "PMID:221442", "title": "[Clear-cell hidradenoma of an unusual location].", "content": "A case of clear cell hidradenoma, which develops from the eccrine glands of the skin, is reported. Specially the histological characteristics, the histogenesis and the unusual localisation of this tumor are described.", "contents": "[Clear-cell hidradenoma of an unusual location]. A case of clear cell hidradenoma, which develops from the eccrine glands of the skin, is reported. Specially the histological characteristics, the histogenesis and the unusual localisation of this tumor are described."}
{"id": "PMID:221443", "title": "[Multilocular extramammary Paget's disease].", "content": "Paget cells were found histologically in a patient with erythemato-erosive lesions on the genitoperineale areas. These cells were also observed in the right axillary skin within a tiny depigmented spot and even in the left axillary skin which was macroscopically almost intact. There were no signs of metastatic or deep-seated adnexal adenocarcinoma. Treatment consisted of radical operation of the pathological lesions with skin grafting and removal of one testicle. After the operation the x-ray irradiation was performed.", "contents": "[Multilocular extramammary Paget's disease]. Paget cells were found histologically in a patient with erythemato-erosive lesions on the genitoperineale areas. These cells were also observed in the right axillary skin within a tiny depigmented spot and even in the left axillary skin which was macroscopically almost intact. There were no signs of metastatic or deep-seated adnexal adenocarcinoma. Treatment consisted of radical operation of the pathological lesions with skin grafting and removal of one testicle. After the operation the x-ray irradiation was performed."}
{"id": "PMID:221444", "title": "[Extramammary Paget's disease].", "content": "A case of extensive extramammary Paget's disease in the scrotum and penis is demonstrated. The disease started a few years before as eczema-like lesions. No underlying carcinoma was found. The surgical excision resulted in a good cosmetic effect.", "contents": "[Extramammary Paget's disease]. A case of extensive extramammary Paget's disease in the scrotum and penis is demonstrated. The disease started a few years before as eczema-like lesions. No underlying carcinoma was found. The surgical excision resulted in a good cosmetic effect."}
{"id": "PMID:221445", "title": "Isolation of picornavirus from feces and semen from an infertile bull.", "content": "Virus was isolated from semen and fecal samples from a bull with orchitis, testicular degeneration, aspermatogenesis, and loss of libido. Both isolates were classified as picornavirus, bovine enterovirus serotype I, on the basis of physical, chemical, and serologic characteristics. Veterinary practitioners that may suspect viral infection as a cause of bovine infertility should submit both semen and fecal samples for virus isolation and identification.", "contents": "Isolation of picornavirus from feces and semen from an infertile bull. Virus was isolated from semen and fecal samples from a bull with orchitis, testicular degeneration, aspermatogenesis, and loss of libido. Both isolates were classified as picornavirus, bovine enterovirus serotype I, on the basis of physical, chemical, and serologic characteristics. Veterinary practitioners that may suspect viral infection as a cause of bovine infertility should submit both semen and fecal samples for virus isolation and identification."}
{"id": "PMID:221447", "title": "Serologic survey for equine infectious anemia virus in Louisiana.", "content": "In 1975, a survey was conducted in East Baton Rouge Parish, Louisiana, to determine the prevalence of equine infectious anemia. Using the agar gel immunodiffusion test, 94 of 1,398 horses (6.7%) were found to be infected. Infection rates were especially high in areas where clinical cases of equine infectious anemia had been diagnosed. Clinical signs compatible with the disease were noted in 1 of the 94 seropositive horses. The sample set of 1,398 horses represented 22% of the census population obtained during the 1971 Venezuelan equine encephalomyelitis vaccination campaign.", "contents": "Serologic survey for equine infectious anemia virus in Louisiana. In 1975, a survey was conducted in East Baton Rouge Parish, Louisiana, to determine the prevalence of equine infectious anemia. Using the agar gel immunodiffusion test, 94 of 1,398 horses (6.7%) were found to be infected. Infection rates were especially high in areas where clinical cases of equine infectious anemia had been diagnosed. Clinical signs compatible with the disease were noted in 1 of the 94 seropositive horses. The sample set of 1,398 horses represented 22% of the census population obtained during the 1971 Venezuelan equine encephalomyelitis vaccination campaign."}
{"id": "PMID:221448", "title": "Group aftercare for chronic schizophrenia.", "content": "This study evaluated the effectiveness of group follow-up in the aftercare of chronic schizophrenia. Fifteen outpatient schizophrenics were reviewed to compare their rehospitalization rates and percentage of time spent in the community during a 2 year period of group aftercare with the 2 year per-group period. Rehospitalization rates were 0.2 admissions/patient year during the group therapy period versus 1.1 admissions/patient year during the pre-group period ( less than .001). Attendance compliance rates during the group therapy were 97%. The results suggest that for these patients, group therapy was an effective method of maintaining schizophrenics in the community.", "contents": "Group aftercare for chronic schizophrenia. This study evaluated the effectiveness of group follow-up in the aftercare of chronic schizophrenia. Fifteen outpatient schizophrenics were reviewed to compare their rehospitalization rates and percentage of time spent in the community during a 2 year period of group aftercare with the 2 year per-group period. Rehospitalization rates were 0.2 admissions/patient year during the group therapy period versus 1.1 admissions/patient year during the pre-group period ( less than .001). Attendance compliance rates during the group therapy were 97%. The results suggest that for these patients, group therapy was an effective method of maintaining schizophrenics in the community."}
{"id": "PMID:221449", "title": "Spin label studies on the interactions of bovine adrenodoxin with NADPH-adrenodoxin reductase and with cytochrome P-450scc.", "content": "Adrenodoxin of bovine adrenocortical mitochondria was spin-labeled with two different spin-labeling reagents, N-(2,2,5,5-tetramethyl-3-carbonylpyrroline-1-oxyl)imidazole (I) and N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyl)maleimide (II), without major loss of its activity for electron transport from NADPH to cytochrome c. The EPR spectrum of adrenodoxin spin-labeled with either of the reagents showed a pattern typical of a moderately immobilized spin label. When adrenodoxin was treated with (I), approximately two amino acid residues per molecule were spin-labeled, whereas a single residue was labeled by (II). While assition of NADPH to adrenodoxin spin-labeled with (I) did not diminish the EPR signal intensity, addition of the reductant to the labeled adrenodoxin in the presence of adrenodoxin reductase caused slow reduction of the spin label, the rate of which was dependent on the aerobicity. Addition of adrenodoxin reductase to adrenodoxin spin-labeled with (I) or (II) resulted in the appearance of a more immobilized component in the EPR spectrum. The ratio of the more immobilized component to the less immobilized component was saturated at a molar ratio of one to one. Addition of cytochrome P-450scc to adrenodoxin labeled with (I) had similar effects on the EPR spectrum.", "contents": "Spin label studies on the interactions of bovine adrenodoxin with NADPH-adrenodoxin reductase and with cytochrome P-450scc. Adrenodoxin of bovine adrenocortical mitochondria was spin-labeled with two different spin-labeling reagents, N-(2,2,5,5-tetramethyl-3-carbonylpyrroline-1-oxyl)imidazole (I) and N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyl)maleimide (II), without major loss of its activity for electron transport from NADPH to cytochrome c. The EPR spectrum of adrenodoxin spin-labeled with either of the reagents showed a pattern typical of a moderately immobilized spin label. When adrenodoxin was treated with (I), approximately two amino acid residues per molecule were spin-labeled, whereas a single residue was labeled by (II). While assition of NADPH to adrenodoxin spin-labeled with (I) did not diminish the EPR signal intensity, addition of the reductant to the labeled adrenodoxin in the presence of adrenodoxin reductase caused slow reduction of the spin label, the rate of which was dependent on the aerobicity. Addition of adrenodoxin reductase to adrenodoxin spin-labeled with (I) or (II) resulted in the appearance of a more immobilized component in the EPR spectrum. The ratio of the more immobilized component to the less immobilized component was saturated at a molar ratio of one to one. Addition of cytochrome P-450scc to adrenodoxin labeled with (I) had similar effects on the EPR spectrum."}
{"id": "PMID:221450", "title": "The interactions between calcium-dependent regulator protein of cyclic nucleotide phosphodiesterase and microtubule proteins. I. Effect of calcium-dependent regulator protein on the calcium sensitivity of microtubule assembly.", "content": "We examined the effect of porcine brain Ca2+-dependent regulator (CDR) protein on microtubule (MT) assembly from microtubular proteins isolated from porcine brain by temperature-dependent cycles of assembly-disassembly. CDR exhibited a potent inhibitory effect on MT assembly in the presence of Ca2+, whereas it had little or no effect on the extent of MT assembly in the absence of Ca2+. The increase in KCl concentration greatly potentiated the Ca2+-dependent inhibitory effect of CDR. The effect of CDR was reversible in a Ca2+ concentration-dependent manner, and the extent of inhibition by CDR at a fixed concentration of free Ca2+ was roughly proportional to the concentration of CDR. Moreover, the Ca2+ concentration required for the half-maximal inhibition of MT assembly from a fixed concentration of purified microtubular proteins (PMP) decreased with increasing CDR concentration. On the basis of these results, together with data on the Ca2+-dependent association of CDR and tubulin (J. Biochem., accompanying paper), we propose the following model; Ca2+ + CDR in equilibrium Ca2+-CDR Ca2+-CDR + tubulin in equilibrium Ca2+-CDR-tubulin (nonpolymerizable).", "contents": "The interactions between calcium-dependent regulator protein of cyclic nucleotide phosphodiesterase and microtubule proteins. I. Effect of calcium-dependent regulator protein on the calcium sensitivity of microtubule assembly. We examined the effect of porcine brain Ca2+-dependent regulator (CDR) protein on microtubule (MT) assembly from microtubular proteins isolated from porcine brain by temperature-dependent cycles of assembly-disassembly. CDR exhibited a potent inhibitory effect on MT assembly in the presence of Ca2+, whereas it had little or no effect on the extent of MT assembly in the absence of Ca2+. The increase in KCl concentration greatly potentiated the Ca2+-dependent inhibitory effect of CDR. The effect of CDR was reversible in a Ca2+ concentration-dependent manner, and the extent of inhibition by CDR at a fixed concentration of free Ca2+ was roughly proportional to the concentration of CDR. Moreover, the Ca2+ concentration required for the half-maximal inhibition of MT assembly from a fixed concentration of purified microtubular proteins (PMP) decreased with increasing CDR concentration. On the basis of these results, together with data on the Ca2+-dependent association of CDR and tubulin (J. Biochem., accompanying paper), we propose the following model; Ca2+ + CDR in equilibrium Ca2+-CDR Ca2+-CDR + tubulin in equilibrium Ca2+-CDR-tubulin (nonpolymerizable)."}
{"id": "PMID:221451", "title": "The interactions between calcium-dependent regulator protein of cyclic nucleotide phosphodiesterase and microtubule proteins. II. Association of calcium-dependent regulator protein with tubulin dimer.", "content": "The Ca2+-dependent regulator protein (CDR) of cyclic nucleotide phosphodiesterase (PDE) was reported to be a Ca2+-dependent regulator of microtubule (MT) assembly in the preceding paper. In this paper, the binding of Ca2+-CDR complex to tubulin dimer was investigated in order to elucidate the Ca2+-dependent inhibitory action of CDR on MT assembly. Purified microtubular proteins (PMPs) isolated from porcine brain did not affect the ability of CDR to activate Ca2+-activatable PDE, and did not include any inhibitory protein of Ca2+-activatable PDE. The binding of CDR to the tubulin dimer was observed on Sephadex G-200 gel filtration and ammonium sulfate fractionation in a Ca2+-dependent manner. CDR did not bind to microtubule associated proteins. We now assume that Ca2+-dependent inhibition of MT assembly by CDR is due to the binding of CDR to tubulin dimer in a Ca2+-dependent manner.", "contents": "The interactions between calcium-dependent regulator protein of cyclic nucleotide phosphodiesterase and microtubule proteins. II. Association of calcium-dependent regulator protein with tubulin dimer. The Ca2+-dependent regulator protein (CDR) of cyclic nucleotide phosphodiesterase (PDE) was reported to be a Ca2+-dependent regulator of microtubule (MT) assembly in the preceding paper. In this paper, the binding of Ca2+-CDR complex to tubulin dimer was investigated in order to elucidate the Ca2+-dependent inhibitory action of CDR on MT assembly. Purified microtubular proteins (PMPs) isolated from porcine brain did not affect the ability of CDR to activate Ca2+-activatable PDE, and did not include any inhibitory protein of Ca2+-activatable PDE. The binding of CDR to the tubulin dimer was observed on Sephadex G-200 gel filtration and ammonium sulfate fractionation in a Ca2+-dependent manner. CDR did not bind to microtubule associated proteins. We now assume that Ca2+-dependent inhibition of MT assembly by CDR is due to the binding of CDR to tubulin dimer in a Ca2+-dependent manner."}
{"id": "PMID:221453", "title": "Use of recombinant plasmids to characterize collagen RNAs in normal and transformed chick embryo fibroblasts.", "content": "Two recombinant plasmids containing chick collagen DNA sequences have been used to characterize messenger RNAs for pro-alpha1 (type I) and pro-alpha2 collagen. Poly(A)-containing RNA from chick embryo calvaria and long bones, tissues which are very active in collagen synthesis, were electrophoresed on agarose gels containing methylmercuric hydroxide and transferred to diazobenzyloxymethyl paper; these covalently bound RNAs were hybridized to 32P-labeled pro-alpha1 or pro-alpha2 collagen DNA sequences derived from the recombinant plasmids. The pro-alpha1 collagen probe identified two RNAs, a major species of 5000 bases and a minor species of 7100 bases; the pro-alpha2 collagen probe hybridized to a major species very similar in size to the pro-alpha1 mRNA, about 5200 bases, and a minor species of 5700 bases. It is possible that the 7100 and 5700 base RNAs represent precursors of pro-alpha1 and pro-alpha2 collagen mRNA, respectively. When similar hybridization experiments were performed with RNA from chick embryo fibroblasts, both the pro-alpha1 and pro-alpha2 collagen mRNAs were observed, as well as their corresponding larger species. With RNAs from fibroblasts transformed by Rous sarcoma virus, however, the levels of all RNA species which hybridized with the pro-alpha1 and pro-alpha2 collagen DNA probes were significantly reduced.", "contents": "Use of recombinant plasmids to characterize collagen RNAs in normal and transformed chick embryo fibroblasts. Two recombinant plasmids containing chick collagen DNA sequences have been used to characterize messenger RNAs for pro-alpha1 (type I) and pro-alpha2 collagen. Poly(A)-containing RNA from chick embryo calvaria and long bones, tissues which are very active in collagen synthesis, were electrophoresed on agarose gels containing methylmercuric hydroxide and transferred to diazobenzyloxymethyl paper; these covalently bound RNAs were hybridized to 32P-labeled pro-alpha1 or pro-alpha2 collagen DNA sequences derived from the recombinant plasmids. The pro-alpha1 collagen probe identified two RNAs, a major species of 5000 bases and a minor species of 7100 bases; the pro-alpha2 collagen probe hybridized to a major species very similar in size to the pro-alpha1 mRNA, about 5200 bases, and a minor species of 5700 bases. It is possible that the 7100 and 5700 base RNAs represent precursors of pro-alpha1 and pro-alpha2 collagen mRNA, respectively. When similar hybridization experiments were performed with RNA from chick embryo fibroblasts, both the pro-alpha1 and pro-alpha2 collagen mRNAs were observed, as well as their corresponding larger species. With RNAs from fibroblasts transformed by Rous sarcoma virus, however, the levels of all RNA species which hybridized with the pro-alpha1 and pro-alpha2 collagen DNA probes were significantly reduced."}
{"id": "PMID:221454", "title": "Declining procollagen mRNA sequences in chick embryo fibroblasts infected with rous sarcoma virus. Correlation with procollagen synthesis.", "content": "Chick cells infected with Rous sarcoma virus are characterized by a wide variety of changes known collectively as transformation. Among these are decreases in the level of procollagen biosynthesis and in the level of procollagen mRNA. In this communication, we examine the time course of the decrease in procollagen biosynthesis, as measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and collagenase assay, and compare it with the decrease in procollagen mRNA sequences measured by hybridization to a complementary DNA. Procollagen biosynthesis and procollagen mRNA sequences decrease simultaneously after infection. Even the initial decrease in procollagen biosynthesis, therefore, is due to a decline in the level of procollagen mRNA.", "contents": "Declining procollagen mRNA sequences in chick embryo fibroblasts infected with rous sarcoma virus. Correlation with procollagen synthesis. Chick cells infected with Rous sarcoma virus are characterized by a wide variety of changes known collectively as transformation. Among these are decreases in the level of procollagen biosynthesis and in the level of procollagen mRNA. In this communication, we examine the time course of the decrease in procollagen biosynthesis, as measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and collagenase assay, and compare it with the decrease in procollagen mRNA sequences measured by hybridization to a complementary DNA. Procollagen biosynthesis and procollagen mRNA sequences decrease simultaneously after infection. Even the initial decrease in procollagen biosynthesis, therefore, is due to a decline in the level of procollagen mRNA."}
{"id": "PMID:221455", "title": "Effects of spermine on activity and stability of calcium-dependent guanosine 3',5'-monophosphate phosphodiesterase.", "content": "Spermine in micromolar concentrations decreased the basal activity of a guanosine 3',5'-monophosphate (cGMP) phosphodiesterase from bovine brain but had no effect in the presence of Ca2+ plus the calcium-dependent regulatory protein (CDR) which increased the activity of the enzyme 4- to 6-fold. Similar effects of spermine were observed on the enzyme at several stages of purification. Spermidine and putrescine were also inhibitory but higher concentrations were required. In the absence of Ca2+ and CDR, the enzyme exhibited two apparent Km values for cGMP (2.5 and 20 microM) which were unaltered by spermine. In the presence of Ca2+ and CDR (when spermine had no effect on activity), a single Km (3.5 microM) was observed. Enzyme purified by chromatography on CDR-Sepharose was rapidly inactivated during incubation at 30 degrees C in 5 mM potassium phosphate buffer (pH 7.0) with EDTA and ethylene glycol bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA). Spermine (20 microM) partially stabilized enzyme activity under these conditions, although it was somewhat less effective than 2 mM MgCl2. The inhibitory effects of spermine (or other polyamines) on basal phosphodiesterase activity, which can be overcome by Ca2+ and CDR, could be important in the regulation of cellular cyclic nucleotide content.", "contents": "Effects of spermine on activity and stability of calcium-dependent guanosine 3',5'-monophosphate phosphodiesterase. Spermine in micromolar concentrations decreased the basal activity of a guanosine 3',5'-monophosphate (cGMP) phosphodiesterase from bovine brain but had no effect in the presence of Ca2+ plus the calcium-dependent regulatory protein (CDR) which increased the activity of the enzyme 4- to 6-fold. Similar effects of spermine were observed on the enzyme at several stages of purification. Spermidine and putrescine were also inhibitory but higher concentrations were required. In the absence of Ca2+ and CDR, the enzyme exhibited two apparent Km values for cGMP (2.5 and 20 microM) which were unaltered by spermine. In the presence of Ca2+ and CDR (when spermine had no effect on activity), a single Km (3.5 microM) was observed. Enzyme purified by chromatography on CDR-Sepharose was rapidly inactivated during incubation at 30 degrees C in 5 mM potassium phosphate buffer (pH 7.0) with EDTA and ethylene glycol bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA). Spermine (20 microM) partially stabilized enzyme activity under these conditions, although it was somewhat less effective than 2 mM MgCl2. The inhibitory effects of spermine (or other polyamines) on basal phosphodiesterase activity, which can be overcome by Ca2+ and CDR, could be important in the regulation of cellular cyclic nucleotide content."}
{"id": "PMID:221458", "title": "Thyroglobulin interactions with thyroid plasma membranes. The existence of specific receptors and their potential role.", "content": "Thyroglobulin binds to isolated thyroid plasma membrane preparations. Binding is pH- and temperature-dependent with 10-fold better binding at pH 5.0 and 37 degrees C than at 0 degrees C and pH 6.0 through pH 7.5. Binding is, however, maximal in 90 min at all pH values and temperatures examined. Although salts can inhibit or enhance thyroglobulin binding depending on the temperature or pH, conditions approaching those of the physiological state are not inhibitory; physiological conditions do inhibit thyrotropin binding to the same membrane preparations. 125I-Labeled thyroglobulin binding is poorly reversed by unlabeled thyroglobulin at all pH values and temperatures studied; excess unlabeled thyroglobulin can, however, readily prevent binding. At pH values greater than 6.0 and at 0 degrees C, the iodine content of thyroglobulin can affect binding, and the 27 S thyroid iodoprotein is relatively ineffective in preventing the binding of the 19 S species. At pH 5.0 and 37 degrees C, there is no difference in binding of highly and less iodinated thyroglobulin, and the 27 S thyroglobulin iodoprotein is effective in preventing 19 S thyroglobulin binding. The complex nature of these results is interpreted in the light of additional data which show (i) that the thyroid membrane recognizes asialothyroglobulin and (ii) that at pH 5.0 and 37 degrees C a membrane-associated neuraminidase is activated which removes sialic acid from thyroglobulin. Vibrio cholerae neuraminidase can substitute for the endogenous neuraminidase. The receptor on thyroid membranes for asialothyroglobulin is similar to the asialoglycoprotein receptor on liver membranes (Morell, A.G., Gregoriadis, G., Scheinberg, I.H., Hickman, J., and Ashwell, G. (1971) J. Biol. Chem. 246, 1461-1467) in that sialic acid on the receptor is critical for receptor expression. It is distinct from the liver asialoglycoprotein receptor in its binding specificity and in its sensitivity to different bacterial and mammalian neuraminidase preparations. Relationships between thyroglobulin and thyrotropin receptors on thyroid membranes are explored, and the functional role of the thyroglobulin receptor is discussed.", "contents": "Thyroglobulin interactions with thyroid plasma membranes. The existence of specific receptors and their potential role. Thyroglobulin binds to isolated thyroid plasma membrane preparations. Binding is pH- and temperature-dependent with 10-fold better binding at pH 5.0 and 37 degrees C than at 0 degrees C and pH 6.0 through pH 7.5. Binding is, however, maximal in 90 min at all pH values and temperatures examined. Although salts can inhibit or enhance thyroglobulin binding depending on the temperature or pH, conditions approaching those of the physiological state are not inhibitory; physiological conditions do inhibit thyrotropin binding to the same membrane preparations. 125I-Labeled thyroglobulin binding is poorly reversed by unlabeled thyroglobulin at all pH values and temperatures studied; excess unlabeled thyroglobulin can, however, readily prevent binding. At pH values greater than 6.0 and at 0 degrees C, the iodine content of thyroglobulin can affect binding, and the 27 S thyroid iodoprotein is relatively ineffective in preventing the binding of the 19 S species. At pH 5.0 and 37 degrees C, there is no difference in binding of highly and less iodinated thyroglobulin, and the 27 S thyroglobulin iodoprotein is effective in preventing 19 S thyroglobulin binding. The complex nature of these results is interpreted in the light of additional data which show (i) that the thyroid membrane recognizes asialothyroglobulin and (ii) that at pH 5.0 and 37 degrees C a membrane-associated neuraminidase is activated which removes sialic acid from thyroglobulin. Vibrio cholerae neuraminidase can substitute for the endogenous neuraminidase. The receptor on thyroid membranes for asialothyroglobulin is similar to the asialoglycoprotein receptor on liver membranes (Morell, A.G., Gregoriadis, G., Scheinberg, I.H., Hickman, J., and Ashwell, G. (1971) J. Biol. Chem. 246, 1461-1467) in that sialic acid on the receptor is critical for receptor expression. It is distinct from the liver asialoglycoprotein receptor in its binding specificity and in its sensitivity to different bacterial and mammalian neuraminidase preparations. Relationships between thyroglobulin and thyrotropin receptors on thyroid membranes are explored, and the functional role of the thyroglobulin receptor is discussed."}
{"id": "PMID:221463", "title": "The activity of 2,4,5-triamino-6-hydroxypyrimidine in the phenylalanine hydroxylase system.", "content": "The pyrimidine moiety of a pterin, 2,4,5-triamino-6-hydroxypyrimidine, has been found to be active in the phenylalanine-hydroxylating system. The phenylalanine-dependent, phenylalanine hydroxylase-catalyzed reaction in the presence of the pyrimidine is largely, but not completely, uncoupled; the ratio of DPNH oxidized to tyrosine formed is about 20 to 1. In addition to the pyrimidine having activity with phenylalanine hydroxylase, a product of the pyrimidine is also a substrate for dihydropteridine reductase. The activity of the pyrimidine with the hydroxylase indicates that neither carbon atoms 6 or 7 of the pterin ring is involved in activation of oxygen during the hydroxylase-catalyzed reaction.", "contents": "The activity of 2,4,5-triamino-6-hydroxypyrimidine in the phenylalanine hydroxylase system. The pyrimidine moiety of a pterin, 2,4,5-triamino-6-hydroxypyrimidine, has been found to be active in the phenylalanine-hydroxylating system. The phenylalanine-dependent, phenylalanine hydroxylase-catalyzed reaction in the presence of the pyrimidine is largely, but not completely, uncoupled; the ratio of DPNH oxidized to tyrosine formed is about 20 to 1. In addition to the pyrimidine having activity with phenylalanine hydroxylase, a product of the pyrimidine is also a substrate for dihydropteridine reductase. The activity of the pyrimidine with the hydroxylase indicates that neither carbon atoms 6 or 7 of the pterin ring is involved in activation of oxygen during the hydroxylase-catalyzed reaction."}
{"id": "PMID:221465", "title": "Interaction of cytochrome c, ferrous ion, and phosphate. Electron transfer within a stoichiometric complex.", "content": "The rate and extent of electron transfer from ferrous ion to ferricytochrome c are enhanced by the presence of inorganic orthophosphate at concentrations comparable to those of reductant and oxidant. Evidence, obtained by the method of continuous variations, shows that the electron transfer occurs within a stoichiometric complex composed of cytochrome c, ferrous ion, and phosphate in molar proportions of about 1:1:1. The incorporation of the anion into this complex appears to result in a modulation of the extent and rate of cytochrome c reduction. The rate of electron transfer obeys a first order rate law, characterized by an apparent first order rate constant of 1.4 min-1. The complex has kinetic significance only; equilibrium dialysis, gel filtration, and sedimentation velocity experiments yielded no evidence for stable binding of phosphate and iron, or of aggregation, on a significant scale. The extent of reduction is limited (for reasons not yet known) to about one-half of the available cytochrome molecules. Reduction in excess of 50% can be achieved only when both, ferrous ion and phosphate, are present in excess of the cytochrome concentration. Kinetic data indicate that reduction to extents over and below 50% occurs by different mechanisms.", "contents": "Interaction of cytochrome c, ferrous ion, and phosphate. Electron transfer within a stoichiometric complex. The rate and extent of electron transfer from ferrous ion to ferricytochrome c are enhanced by the presence of inorganic orthophosphate at concentrations comparable to those of reductant and oxidant. Evidence, obtained by the method of continuous variations, shows that the electron transfer occurs within a stoichiometric complex composed of cytochrome c, ferrous ion, and phosphate in molar proportions of about 1:1:1. The incorporation of the anion into this complex appears to result in a modulation of the extent and rate of cytochrome c reduction. The rate of electron transfer obeys a first order rate law, characterized by an apparent first order rate constant of 1.4 min-1. The complex has kinetic significance only; equilibrium dialysis, gel filtration, and sedimentation velocity experiments yielded no evidence for stable binding of phosphate and iron, or of aggregation, on a significant scale. The extent of reduction is limited (for reasons not yet known) to about one-half of the available cytochrome molecules. Reduction in excess of 50% can be achieved only when both, ferrous ion and phosphate, are present in excess of the cytochrome concentration. Kinetic data indicate that reduction to extents over and below 50% occurs by different mechanisms."}
{"id": "PMID:221467", "title": "Purification and properties of fructose-1,6-bisphosphatase of Bacillus subtilis.", "content": "Fructose-1,6-bisphosphatase (D-fructose-1,6-bisphosphate 1-phosphohydrase, EC 3.1.3.11) of Bacillus subtilis is a constitutive enzyme that was purified 1000-fold (30% yield) to 80% purity as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis where it exhibits a band corresponding to 72,000 daltons. It sediments at 15 S in sucrose density gradients indicating a molecular weight of 380,000, but apparently is very asymmetric. Its activity is irreversibly inactivated in the absence of Mn2+. The enzyme specifically catalyzes dephosphorylation of D-fructose 1,6-bisphosphate with a pH optimum of 8.0. It has 40 to 60% of full activity in the absence of P-enolpyruvate; 20 microM P-enolpyruvate activates it maximally. High concentrations of monovalent cations also activate, NH4+ being most effective. Inhibitors fall into two groups. 1) Nucleoside monophosphates, phosphorylated coenzymes, and polynucleotides inhibit competitively with P-enolpyruvate (AMP (Ki = 2 microM) and dAMP are most effective). 2) The inhibition by nucleoside di- and triphosphates, PPi, and highly phosphorylated nucleotides (guanosine 5'-triphosphate 3'-diphosphate (pppGpp) and adenosine 5'-triphosphate 3'-diphosphate are most effective) is not competed by P-enolpyruvate but is partially overcome by fructose 1,6-bisphosphate (2 microM). Therefore, highly phosphorylated nucleotides (pppGpp and others), produced in over 0.2 mM concentrations upon step down from fast to slow growth rates (Gallant, J., and Lazzarini, R.A. (1976) in Protein Synthesis (McConkey, E.H., ed) Vol. 2, pp. 309-349, Marcel Dekker, Inc., New York), can reduce the conversion rate of fructose 1,6-bisphosphate to fructose 6-phosphate during gluconeogenesis. Comparing glycolytic growth on D-glucose and gluconeogenic growth on L-malate, the intracellular concentrations of fructose 1,6-bisphosphate differ but are both above the Km (13 microM) of the enzyme, those of AMP are similar, whereas those of P-enolpyruvate (0.18 mM versus 1.3 mM) indicate that the enzyme has only 40% of its full activity during glycolysis; nucleotides other than AMP may inhibit additionally. Thus, the futile cycle of fructose 1,6-bisphosphate synthesis and degradation during glycolysis is partially avoided, but the cells are poised for rapid adaptation upon change to gluconeogenic growth conditions.", "contents": "Purification and properties of fructose-1,6-bisphosphatase of Bacillus subtilis. Fructose-1,6-bisphosphatase (D-fructose-1,6-bisphosphate 1-phosphohydrase, EC 3.1.3.11) of Bacillus subtilis is a constitutive enzyme that was purified 1000-fold (30% yield) to 80% purity as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis where it exhibits a band corresponding to 72,000 daltons. It sediments at 15 S in sucrose density gradients indicating a molecular weight of 380,000, but apparently is very asymmetric. Its activity is irreversibly inactivated in the absence of Mn2+. The enzyme specifically catalyzes dephosphorylation of D-fructose 1,6-bisphosphate with a pH optimum of 8.0. It has 40 to 60% of full activity in the absence of P-enolpyruvate; 20 microM P-enolpyruvate activates it maximally. High concentrations of monovalent cations also activate, NH4+ being most effective. Inhibitors fall into two groups. 1) Nucleoside monophosphates, phosphorylated coenzymes, and polynucleotides inhibit competitively with P-enolpyruvate (AMP (Ki = 2 microM) and dAMP are most effective). 2) The inhibition by nucleoside di- and triphosphates, PPi, and highly phosphorylated nucleotides (guanosine 5'-triphosphate 3'-diphosphate (pppGpp) and adenosine 5'-triphosphate 3'-diphosphate are most effective) is not competed by P-enolpyruvate but is partially overcome by fructose 1,6-bisphosphate (2 microM). Therefore, highly phosphorylated nucleotides (pppGpp and others), produced in over 0.2 mM concentrations upon step down from fast to slow growth rates (Gallant, J., and Lazzarini, R.A. (1976) in Protein Synthesis (McConkey, E.H., ed) Vol. 2, pp. 309-349, Marcel Dekker, Inc., New York), can reduce the conversion rate of fructose 1,6-bisphosphate to fructose 6-phosphate during gluconeogenesis. Comparing glycolytic growth on D-glucose and gluconeogenic growth on L-malate, the intracellular concentrations of fructose 1,6-bisphosphate differ but are both above the Km (13 microM) of the enzyme, those of AMP are similar, whereas those of P-enolpyruvate (0.18 mM versus 1.3 mM) indicate that the enzyme has only 40% of its full activity during glycolysis; nucleotides other than AMP may inhibit additionally. Thus, the futile cycle of fructose 1,6-bisphosphate synthesis and degradation during glycolysis is partially avoided, but the cells are poised for rapid adaptation upon change to gluconeogenic growth conditions."}
{"id": "PMID:221470", "title": "Vesicular stomatitis virus infection reduces the number of active DNA-dependent RNA polymerases in myeloma cells.", "content": "Infection of mouse myeloma (MPC-11) cells with vesicular stomatitis virus resulted in rapid loss in activity of cellular RNA polymerases associated with nuclear chromatin. No RNA polymerase inhibitor could be detected in extracts of infected cell nuclei. Reconstitution experiments with solubilized RNA polymerases dissociated from chromatin of infected and uninfected cells demonstrated that vesicular stomatitis viral infection did not affect the ability of the polymerases to function on endogenous or exogenous templates; nor did infection alter the template capability of the chromatin. Measurement of the number of actively growing RNA chains revealed that infected cell nuclei contained fewer active polymerase units; however, the rates of RNA chain elongation were the same in nuclei from infected and uninfected cells. Quantitation of the number of polymerase units active in nuclear chromatin revealed that the alpha-amantin-sensitive polymerase II was more severely reduced by viral infection than were polymerases I and III.", "contents": "Vesicular stomatitis virus infection reduces the number of active DNA-dependent RNA polymerases in myeloma cells. Infection of mouse myeloma (MPC-11) cells with vesicular stomatitis virus resulted in rapid loss in activity of cellular RNA polymerases associated with nuclear chromatin. No RNA polymerase inhibitor could be detected in extracts of infected cell nuclei. Reconstitution experiments with solubilized RNA polymerases dissociated from chromatin of infected and uninfected cells demonstrated that vesicular stomatitis viral infection did not affect the ability of the polymerases to function on endogenous or exogenous templates; nor did infection alter the template capability of the chromatin. Measurement of the number of actively growing RNA chains revealed that infected cell nuclei contained fewer active polymerase units; however, the rates of RNA chain elongation were the same in nuclei from infected and uninfected cells. Quantitation of the number of polymerase units active in nuclear chromatin revealed that the alpha-amantin-sensitive polymerase II was more severely reduced by viral infection than were polymerases I and III."}
{"id": "PMID:221473", "title": "Hormone-stimulated phosphorylation of liver phosphofructokinase in vivo.", "content": "The effect of glucagon on the phosphorylation and the enzymic activity of phosphofructokinase in rat liver in vivo was investigated. Glucagon stimulated the phosphorylation of liver phosphofructokinase approximately 3- to 5-fold and increased cAMP levels 5-fold and blood glucose levels 2-fold over the values obtained for control animals. The specific radioactivity of ATP isolated from liver was the same in both control and hormone-treated animals. During the purification of the 32P-labeled enzyme from both animals, no difference was observed in the total or specific enzyme activities of the enzymes from the various fractions. Thus, phosphofructokinase appears to be phosphorylated in vivo by a cyclic AMP-dependent protein kinase. Although phosphorylation does not affect the maximum catalytic activity of the enzyme, it does render the enzyme significantly more sensitive to ATP inhibition. Thus, at a given concentration of ATP, the phosphorylated phosphofructokinase exhibits considerably lower activity than the unphosphorylated enzyme. The possible relationship between our observations and glucagon-mediated control of glycolysis is discussed.", "contents": "Hormone-stimulated phosphorylation of liver phosphofructokinase in vivo. The effect of glucagon on the phosphorylation and the enzymic activity of phosphofructokinase in rat liver in vivo was investigated. Glucagon stimulated the phosphorylation of liver phosphofructokinase approximately 3- to 5-fold and increased cAMP levels 5-fold and blood glucose levels 2-fold over the values obtained for control animals. The specific radioactivity of ATP isolated from liver was the same in both control and hormone-treated animals. During the purification of the 32P-labeled enzyme from both animals, no difference was observed in the total or specific enzyme activities of the enzymes from the various fractions. Thus, phosphofructokinase appears to be phosphorylated in vivo by a cyclic AMP-dependent protein kinase. Although phosphorylation does not affect the maximum catalytic activity of the enzyme, it does render the enzyme significantly more sensitive to ATP inhibition. Thus, at a given concentration of ATP, the phosphorylated phosphofructokinase exhibits considerably lower activity than the unphosphorylated enzyme. The possible relationship between our observations and glucagon-mediated control of glycolysis is discussed."}
{"id": "PMID:221474", "title": "Processing and function of undermethylated chicken embryo fibroblast mRNA.", "content": "Cycloleucine (1-aminocyclopentane-1-carboxylic acid) is a potent inhibitor of RNA methylation in B77 sarcoma virus-infected chicken embryo fibroblasts. Under conditions where 40 mM cycloleucine is present, internal N-6-methyladenosine and 5'-terminal cap 2'-O-ribose methylations of poly(A)+ RNA are inhibited greater than 90%. The methylation of the 5'-terminal 7-methylguanosine, however, does not appear to be significantly affected. The poly(A)+ RNA synthesized in cycloleucine-treated cells is transported from the nucleus to the cytoplasm and associates with polyribosomes at rates comparable to poly(A)+ RNA in untreated cells. On the other hand, the transport and utilization of newly synthesized ribosomal RNA in cycloleucine-treated cells is impaired, and the accumulation of mature 18 S and 28 S rRNA is reduced.", "contents": "Processing and function of undermethylated chicken embryo fibroblast mRNA. Cycloleucine (1-aminocyclopentane-1-carboxylic acid) is a potent inhibitor of RNA methylation in B77 sarcoma virus-infected chicken embryo fibroblasts. Under conditions where 40 mM cycloleucine is present, internal N-6-methyladenosine and 5'-terminal cap 2'-O-ribose methylations of poly(A)+ RNA are inhibited greater than 90%. The methylation of the 5'-terminal 7-methylguanosine, however, does not appear to be significantly affected. The poly(A)+ RNA synthesized in cycloleucine-treated cells is transported from the nucleus to the cytoplasm and associates with polyribosomes at rates comparable to poly(A)+ RNA in untreated cells. On the other hand, the transport and utilization of newly synthesized ribosomal RNA in cycloleucine-treated cells is impaired, and the accumulation of mature 18 S and 28 S rRNA is reduced."}
{"id": "PMID:221475", "title": "A protein activator for the adenylate cyclase of Bordetella pertussis.", "content": "The activity of Bordetella pertussis extracytoplasmic adenylate cyclase is 100-fold higher in organisms grown on blood agar than in those grown in synthetic medium. This increase in activity is due to in vivo activation of the enzyme by a factor present in erythrocytes. Activation also occurs in killed or disrupted organisms. The activator can be separated from heme proteins and has been purified approximately 100-fold from erythrocytes, yielding material of approximately 105,000 daltons. It is sensitive to trypsin and alpha-chymotrypsin and exhibits considerable heat stability. Activation of cyclase in intact B. pertussis organisms exhibits a lag of 3 to 4 min and is not reversed by washing. Response to the activator decreases with increasing purification of the adenylate cyclase and is absent in the pure enzyme. The activation does not appear to be proteolytic and does not appear to change access to the substrate, ATP. The activator has no effect on a number of eukaryotic cyclases. We conclude that this is a new type of activation and that the activator differs from all those previously described.", "contents": "A protein activator for the adenylate cyclase of Bordetella pertussis. The activity of Bordetella pertussis extracytoplasmic adenylate cyclase is 100-fold higher in organisms grown on blood agar than in those grown in synthetic medium. This increase in activity is due to in vivo activation of the enzyme by a factor present in erythrocytes. Activation also occurs in killed or disrupted organisms. The activator can be separated from heme proteins and has been purified approximately 100-fold from erythrocytes, yielding material of approximately 105,000 daltons. It is sensitive to trypsin and alpha-chymotrypsin and exhibits considerable heat stability. Activation of cyclase in intact B. pertussis organisms exhibits a lag of 3 to 4 min and is not reversed by washing. Response to the activator decreases with increasing purification of the adenylate cyclase and is absent in the pure enzyme. The activation does not appear to be proteolytic and does not appear to change access to the substrate, ATP. The activator has no effect on a number of eukaryotic cyclases. We conclude that this is a new type of activation and that the activator differs from all those previously described."}
{"id": "PMID:221476", "title": "Testicular steroidogenesis after human chorionic gonadotropin desensitization in rats.", "content": "When a single injection of 500 I.U. of human chorionic gonadotropin (hCG) is given to rats there is an initial acute rise of plasma testosterone and of testicular content for both cyclic AMP and testosterone. This response correlates with an increase in both lyase and 17 alpha-hydroxylase activities. Thereafter both plasma and testicular testosterone decline and do not increase after a second injection of hCG. During this period of desensitization, isolated Leydig cells were insensitive to the steroidogenic stimulatory effect of both hCG and dibutyryl cyclic AMP. The post-cyclic AMP block is not due to an alteration of the cyclic AMP-dependent protein kinase but it is correlated with a decrease in both lyase and 17 alpha-hydroxylase activities of the Leydig cell's microsomes. This decrease is not caused by the absence of the recently described cytosol activator of this enzyme because its addition did not restore the enzymatic activity. Within 60 to 96 h after hCG injection there was a spontaneous increase of both plasma and testicular testosterone and this parallels the recovery of lyase and 17 alpha-hydroxylase activities. These results suggest that both enzymatic activities are regulated, directly or indirectly, by hCG, and that this is partly responsible for the hCG-induced steroidogenic refractoriness of Leydig cells.", "contents": "Testicular steroidogenesis after human chorionic gonadotropin desensitization in rats. When a single injection of 500 I.U. of human chorionic gonadotropin (hCG) is given to rats there is an initial acute rise of plasma testosterone and of testicular content for both cyclic AMP and testosterone. This response correlates with an increase in both lyase and 17 alpha-hydroxylase activities. Thereafter both plasma and testicular testosterone decline and do not increase after a second injection of hCG. During this period of desensitization, isolated Leydig cells were insensitive to the steroidogenic stimulatory effect of both hCG and dibutyryl cyclic AMP. The post-cyclic AMP block is not due to an alteration of the cyclic AMP-dependent protein kinase but it is correlated with a decrease in both lyase and 17 alpha-hydroxylase activities of the Leydig cell's microsomes. This decrease is not caused by the absence of the recently described cytosol activator of this enzyme because its addition did not restore the enzymatic activity. Within 60 to 96 h after hCG injection there was a spontaneous increase of both plasma and testicular testosterone and this parallels the recovery of lyase and 17 alpha-hydroxylase activities. These results suggest that both enzymatic activities are regulated, directly or indirectly, by hCG, and that this is partly responsible for the hCG-induced steroidogenic refractoriness of Leydig cells."}
{"id": "PMID:221479", "title": "An adenosine 3':5'-monophosphate-dependent protein kinase from the human erythrocyte membrane. Purification and characterization.", "content": "An adenosine 3':5'-monophosphate-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37) has been isolated from the human erythrocyte memebrane and the phosphotransferase activity exhibited by this enzyme has been purified 800-fold. In concentrated solutions, the membrane-derived protein kinase undergoes aggregation with a concomitant loss in observed phosphotransferase activity. This loss of activity can be restored by means of inducing deaggregation. The phosphotransferase activity of the protein kinase is virtually obliterated in the presence of high (300 mM) concentrations of sodium chloride. This effect is also reversible. The pH optimum for the phosphotransferase reaction that is catalyzed by the membrane-derived protein kinase is approximately 8. Micromolar concentrations of cAMP are optimal with respect to promoting the phosphotransferase reaction. Initial velocity and product inhibition studies were conducted on the cAMP-independent protein kinase derived from the cAMP-dependent enzyme. These studies indicate that the phosphotransferase reaction proceeds by a sequential kinetic mechanism.", "contents": "An adenosine 3':5'-monophosphate-dependent protein kinase from the human erythrocyte membrane. Purification and characterization. An adenosine 3':5'-monophosphate-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37) has been isolated from the human erythrocyte memebrane and the phosphotransferase activity exhibited by this enzyme has been purified 800-fold. In concentrated solutions, the membrane-derived protein kinase undergoes aggregation with a concomitant loss in observed phosphotransferase activity. This loss of activity can be restored by means of inducing deaggregation. The phosphotransferase activity of the protein kinase is virtually obliterated in the presence of high (300 mM) concentrations of sodium chloride. This effect is also reversible. The pH optimum for the phosphotransferase reaction that is catalyzed by the membrane-derived protein kinase is approximately 8. Micromolar concentrations of cAMP are optimal with respect to promoting the phosphotransferase reaction. Initial velocity and product inhibition studies were conducted on the cAMP-independent protein kinase derived from the cAMP-dependent enzyme. These studies indicate that the phosphotransferase reaction proceeds by a sequential kinetic mechanism."}
{"id": "PMID:221480", "title": "Total synthesis of a tyrosine suppressor transfer RNA gene. XIII. Synthesis of deoxyribopolynucleotide segments corresponding to the nucleotide sequence -1 to -29 in the promoter region.", "content": "Chemical syntheses of two tridecanucleotides, d(G-C-A-T-C-A-T-A-T-C-A-A-A) and d(G-C-G-T-C-A-T-T-T-G-A-T-A), and three undecanucleotides, d(G-G-A-A-G-C-G-G-G-G-C), d(T-G-A-T-G-C-G-C-C-C-C), and d(T-G-A-C-G-C-G-C-C-G-C), are described. These deoxyribo-oligonucleotide segments together represent the DNA duplex corresponding to the previously determined nucleotide sequence -1 to -29 of the promoter region of the tyrosine tRNA gene (Sekiya, T., van Ormondt, H., and Khorana, H.G. (1975) J. Biol. Chem. 250, 1087-1098). Chemical syntheses used the principles of stepwise addition of protected mono- and oligonucleotides to the 3'-hydroxyl end of growing oligonucleotide chains. The desired condensation products were isolated by solvent extraction methods in the case of di- and trincleotides and by anion exchange chromatography in the case of longer chains. All the five synthetic oligonucleotides were characterized by chromatographic and radioactive fingerprinting methods after labeling at the 5'-ends with a [32P]phosphate group.", "contents": "Total synthesis of a tyrosine suppressor transfer RNA gene. XIII. Synthesis of deoxyribopolynucleotide segments corresponding to the nucleotide sequence -1 to -29 in the promoter region. Chemical syntheses of two tridecanucleotides, d(G-C-A-T-C-A-T-A-T-C-A-A-A) and d(G-C-G-T-C-A-T-T-T-G-A-T-A), and three undecanucleotides, d(G-G-A-A-G-C-G-G-G-G-C), d(T-G-A-T-G-C-G-C-C-C-C), and d(T-G-A-C-G-C-G-C-C-G-C), are described. These deoxyribo-oligonucleotide segments together represent the DNA duplex corresponding to the previously determined nucleotide sequence -1 to -29 of the promoter region of the tyrosine tRNA gene (Sekiya, T., van Ormondt, H., and Khorana, H.G. (1975) J. Biol. Chem. 250, 1087-1098). Chemical syntheses used the principles of stepwise addition of protected mono- and oligonucleotides to the 3'-hydroxyl end of growing oligonucleotide chains. The desired condensation products were isolated by solvent extraction methods in the case of di- and trincleotides and by anion exchange chromatography in the case of longer chains. All the five synthetic oligonucleotides were characterized by chromatographic and radioactive fingerprinting methods after labeling at the 5'-ends with a [32P]phosphate group."}
{"id": "PMID:221481", "title": "Total synthesis of a tyrosine suppressor transfer RNA gene. XVI. Enzymatic joinings to form the total 207-base pair-long DNA.", "content": "The total synthesis of a 207-base pair-long DNA, which is biologically functional as a tyrosine suppressor transfer RNA gene, has been completed. The synthesis involved the enzymatic joining of the previously synthesized duplexes. Thus, the duplex corresponding to the promoter region [P] (Sekiya, T., Brown, E.L., Ramamoorthy, B., Fritz, H.-J., Gait, M.J., Lees, R.G., Ryan, M.J., Khorana, H.G., and Norris, K.E. (1979) J. Biol. Chem. 254, 5781-5786) was jointed to Duplex [I] (Caruthers, M.H., Kleppe, R., Kleppe, K., and Khorana, H.G. (1976) J. Biol Chem. 251, 658-666) to form [P + I]. Separatively, Duplex [III + IV + Vb] was prepared from the previously described Duplexes [III], [IV], and [Vb]. (Loewen, P.C., Miller, R.C., Panet, A., Sekiya, T., and Khorana, H.G. (1976) J. Biol. Chem. 251, 642-650; Sekiya, T., Besmer, P., Takeya, T., and Khorana, H.G. 1976) J. Biol. Chem. 251, 634-641; Ramamoorthy, B., Lees, R.G., Kleid, D., and Khorana, H.G., (1976) J. Biol Chem. 251, 676-694). The product [P + I], was joined to Duplex [II] (Panet, A., Kleppe, R., Kleppe, K., and Khorana, H.G. (1976) J. Biol. Chem. 251, 651-657) and then to [III + IV + Vb] without isolation of the intermediates. In all the above joinings, the duplexes carried 32P-labeled phosphate groups at the appropriate 5'-ends. The total DNA and the intermediate duplexes were all characterized by their relative mobilities in electrophoresis on polyacrylamide gel slabs, by nearest neighbor analysis, and by degradation to 5'-nucleotides of radioactively labeled joined products. Two succeeding papers describe the transcription in vitro and the suppressor activity in vivo, of the synthetic gene now described.", "contents": "Total synthesis of a tyrosine suppressor transfer RNA gene. XVI. Enzymatic joinings to form the total 207-base pair-long DNA. The total synthesis of a 207-base pair-long DNA, which is biologically functional as a tyrosine suppressor transfer RNA gene, has been completed. The synthesis involved the enzymatic joining of the previously synthesized duplexes. Thus, the duplex corresponding to the promoter region [P] (Sekiya, T., Brown, E.L., Ramamoorthy, B., Fritz, H.-J., Gait, M.J., Lees, R.G., Ryan, M.J., Khorana, H.G., and Norris, K.E. (1979) J. Biol. Chem. 254, 5781-5786) was jointed to Duplex [I] (Caruthers, M.H., Kleppe, R., Kleppe, K., and Khorana, H.G. (1976) J. Biol Chem. 251, 658-666) to form [P + I]. Separatively, Duplex [III + IV + Vb] was prepared from the previously described Duplexes [III], [IV], and [Vb]. (Loewen, P.C., Miller, R.C., Panet, A., Sekiya, T., and Khorana, H.G. (1976) J. Biol. Chem. 251, 642-650; Sekiya, T., Besmer, P., Takeya, T., and Khorana, H.G. 1976) J. Biol. Chem. 251, 634-641; Ramamoorthy, B., Lees, R.G., Kleid, D., and Khorana, H.G., (1976) J. Biol Chem. 251, 676-694). The product [P + I], was joined to Duplex [II] (Panet, A., Kleppe, R., Kleppe, K., and Khorana, H.G. (1976) J. Biol. Chem. 251, 651-657) and then to [III + IV + Vb] without isolation of the intermediates. In all the above joinings, the duplexes carried 32P-labeled phosphate groups at the appropriate 5'-ends. The total DNA and the intermediate duplexes were all characterized by their relative mobilities in electrophoresis on polyacrylamide gel slabs, by nearest neighbor analysis, and by degradation to 5'-nucleotides of radioactively labeled joined products. Two succeeding papers describe the transcription in vitro and the suppressor activity in vivo, of the synthetic gene now described."}
{"id": "PMID:221482", "title": "The amino acid sequence of fragment A, an enzymically active fragment of diphtheria toxin. I. The tryptic peptides from the maleylated protein.", "content": "Six tryptic peptides ranging in size from 3 to 126 residues were isolated from maleylated Fragment A of diphtheria toxin after tryptic hydrolysis. These peptides accounted for all 193 residues found by amino acid analysis. After demaleylation, the six peptides were purified by chromatography on Sephadex G-50, coupled with paper chromatography and electrophoresis, and were analyzed by various methods. The compositions and properties of the peptides are reported. Almost 70% of the residues were positioned within these peptides.", "contents": "The amino acid sequence of fragment A, an enzymically active fragment of diphtheria toxin. I. The tryptic peptides from the maleylated protein. Six tryptic peptides ranging in size from 3 to 126 residues were isolated from maleylated Fragment A of diphtheria toxin after tryptic hydrolysis. These peptides accounted for all 193 residues found by amino acid analysis. After demaleylation, the six peptides were purified by chromatography on Sephadex G-50, coupled with paper chromatography and electrophoresis, and were analyzed by various methods. The compositions and properties of the peptides are reported. Almost 70% of the residues were positioned within these peptides."}
{"id": "PMID:221483", "title": "The amino acid sequence of fragment A, an enzymically active fragment of diphtheria toxin. II. The cyanogen bromide peptides.", "content": "Cyanogen bromide cleavage of Fragment A from diphtheria toxin at the four methionines present in each molecule resulted in five major peptides which were isolated and studied by sequence methods. These five peptides of 4, 11, 14, 63, and 101 residues account for all 193 residues in Fragment A and provide overlaps for the tryptic peptides from the maleylated protein. Two additional peptides were isolated and shown to be shorter forms (8 and 10 residues) of the COOH-terminal cyanogen bromide peptide (11 residues).", "contents": "The amino acid sequence of fragment A, an enzymically active fragment of diphtheria toxin. II. The cyanogen bromide peptides. Cyanogen bromide cleavage of Fragment A from diphtheria toxin at the four methionines present in each molecule resulted in five major peptides which were isolated and studied by sequence methods. These five peptides of 4, 11, 14, 63, and 101 residues account for all 193 residues in Fragment A and provide overlaps for the tryptic peptides from the maleylated protein. Two additional peptides were isolated and shown to be shorter forms (8 and 10 residues) of the COOH-terminal cyanogen bromide peptide (11 residues)."}
{"id": "PMID:221484", "title": "The amino acid sequence of fragment A, an enzymically active fragment of diphtheria toxin. III. The chymotryptic peptides, the peptides derived by cleavage at tryptophan residues, and the complete sequence of the protein.", "content": "Fragment A (21,145 daltons in its longest known form) may be derived from diphtheria toxin (60,000 daltons) by mild tryptic digestion and reduction. Purified Fragment A consists of a mixture of 3 molecules of 190, 192, and 193 residues; the first 190 residues are in common and correspond to the NH2-terminal region the toxin. All three species of Fragment A are active in catalyzing ADP ribosylation of elongation factor 2, an essential component of protein synthesis. This reaction inactivates the factor and is responsible for the toxin's action in inhibiting protein synthesis in animal cells. It is believed that Fragment A or similar enzymically active fragments released into the cytosol of toxin-treated cells mediate this inhibition. The complete amino acid sequence of Fragment A has been determined from 32 chymotryptic peptides, three peptides derived by chemical cleavage of Fragment A at its 2 tryptophan residues, five cyanogen bromide peptides, and six tryptic peptides from the maleylated protein.", "contents": "The amino acid sequence of fragment A, an enzymically active fragment of diphtheria toxin. III. The chymotryptic peptides, the peptides derived by cleavage at tryptophan residues, and the complete sequence of the protein. Fragment A (21,145 daltons in its longest known form) may be derived from diphtheria toxin (60,000 daltons) by mild tryptic digestion and reduction. Purified Fragment A consists of a mixture of 3 molecules of 190, 192, and 193 residues; the first 190 residues are in common and correspond to the NH2-terminal region the toxin. All three species of Fragment A are active in catalyzing ADP ribosylation of elongation factor 2, an essential component of protein synthesis. This reaction inactivates the factor and is responsible for the toxin's action in inhibiting protein synthesis in animal cells. It is believed that Fragment A or similar enzymically active fragments released into the cytosol of toxin-treated cells mediate this inhibition. The complete amino acid sequence of Fragment A has been determined from 32 chymotryptic peptides, three peptides derived by chemical cleavage of Fragment A at its 2 tryptophan residues, five cyanogen bromide peptides, and six tryptic peptides from the maleylated protein."}
{"id": "PMID:221485", "title": "Enzymic activity of cholera toxin. II. Relationships to proteolytic processing, disulfide bond reduction, and subunit composition.", "content": "Cholera toxin containing intact A chain (Mr = 29,000) was isolated, and its enzymic properties were characterized. The \"unnicked\" form of the toxin, produced by a protease-deficient, hypertoxinogenic mutant of Vibrio cholerae 569B, had greatly reduced activity in catalyzing the NAD+-glycohydrolase and ADP-ribosyltransferase reactions as compared to the naturally nicked form commonly isolated. In the latter, the intact A chain has been cleaved by bacterial proteases to yield disulfide-linked A1 and A2 chains (Mr = 23,000 and 6,000, respectively). Digestion of unnicked toxin with trypsin or elastase yielded a nicked form similar to or identical with the naturally nicked toxin, but chymotryptic digestion did not. Disulfide bond reduction was necessary for expression of enzymic activity by naturally nicked or trypsin-nicked toxin, or the A1A2 protomer. Fractionation of thiol-treated, nicked cholera toxin by ion exchange, molecular exclusion, or affinity chromatography gave results suggesting that the reduced toxin displays enzymic activity while remaining structurally intact.", "contents": "Enzymic activity of cholera toxin. II. Relationships to proteolytic processing, disulfide bond reduction, and subunit composition. Cholera toxin containing intact A chain (Mr = 29,000) was isolated, and its enzymic properties were characterized. The \"unnicked\" form of the toxin, produced by a protease-deficient, hypertoxinogenic mutant of Vibrio cholerae 569B, had greatly reduced activity in catalyzing the NAD+-glycohydrolase and ADP-ribosyltransferase reactions as compared to the naturally nicked form commonly isolated. In the latter, the intact A chain has been cleaved by bacterial proteases to yield disulfide-linked A1 and A2 chains (Mr = 23,000 and 6,000, respectively). Digestion of unnicked toxin with trypsin or elastase yielded a nicked form similar to or identical with the naturally nicked toxin, but chymotryptic digestion did not. Disulfide bond reduction was necessary for expression of enzymic activity by naturally nicked or trypsin-nicked toxin, or the A1A2 protomer. Fractionation of thiol-treated, nicked cholera toxin by ion exchange, molecular exclusion, or affinity chromatography gave results suggesting that the reduced toxin displays enzymic activity while remaining structurally intact."}
{"id": "PMID:221486", "title": "Structure of the lipopolysaccharide from an Escherichia coli heptose-less mutant. I. Chemical degradations and identification of products.", "content": "The structure of lipopolysaccharide from a heptose-less mutant of Escherichia coli K-12 has been investigated. Lipopolysaccharide isolated from 32P-labeled cells was treated with mild alkali to yield two separable components: [OH-LPS]-I (approximately 70%) and [OH-LPS]-II (approximately 30%). Mild acidic treatment of [OH-LPS]-I gave mainly a product which was identified as (4-O-phosphoryl-N-beta-hydroxymyristyl-D-glucosaminyl)-beta(1 leads to 6)-N-beta-hydroxymyristyl-D-glucosamine 1-phosphate (Compound I). Further acidic hydrolysis of both [OH-LPS]-I and [OH-LPS]-II yielded as the main product (4-O-phosphoryl-N-beta-hydroxymyristyl-D-glucosaminyl)-beta(1 leads to 6)-N-beta-hydroxymyristyl-D-glucosamine (Compound II). The structures of the above products were deduced by a combination of compositional analyses, sensitivity to phosphomonoesterase, rates of hydrolysis of the phosphate groups and alkali-catalyzed beta elimination of the phosphate residues following appropriate oxidation of hydroxyl groups. These studies together with work reported in the accompanying papers have led to the identification of two species of lipopolysaccharide in the E. coli strain both of which contain a single glucosamine dissacharide unit but differ in having monosubstituted phosphate or pyrophosphate groups at the glycosidic position. Each species of lipopolysaccharide also appeared to be heterogeneous with respect to the number of esterified fatty acyl groups.", "contents": "Structure of the lipopolysaccharide from an Escherichia coli heptose-less mutant. I. Chemical degradations and identification of products. The structure of lipopolysaccharide from a heptose-less mutant of Escherichia coli K-12 has been investigated. Lipopolysaccharide isolated from 32P-labeled cells was treated with mild alkali to yield two separable components: [OH-LPS]-I (approximately 70%) and [OH-LPS]-II (approximately 30%). Mild acidic treatment of [OH-LPS]-I gave mainly a product which was identified as (4-O-phosphoryl-N-beta-hydroxymyristyl-D-glucosaminyl)-beta(1 leads to 6)-N-beta-hydroxymyristyl-D-glucosamine 1-phosphate (Compound I). Further acidic hydrolysis of both [OH-LPS]-I and [OH-LPS]-II yielded as the main product (4-O-phosphoryl-N-beta-hydroxymyristyl-D-glucosaminyl)-beta(1 leads to 6)-N-beta-hydroxymyristyl-D-glucosamine (Compound II). The structures of the above products were deduced by a combination of compositional analyses, sensitivity to phosphomonoesterase, rates of hydrolysis of the phosphate groups and alkali-catalyzed beta elimination of the phosphate residues following appropriate oxidation of hydroxyl groups. These studies together with work reported in the accompanying papers have led to the identification of two species of lipopolysaccharide in the E. coli strain both of which contain a single glucosamine dissacharide unit but differ in having monosubstituted phosphate or pyrophosphate groups at the glycosidic position. Each species of lipopolysaccharide also appeared to be heterogeneous with respect to the number of esterified fatty acyl groups."}
{"id": "PMID:221487", "title": "Cytochrome c peroxidase. Interconversion of chemically and enzymatically reactive and unreactive forms of the ferric protein.", "content": "Ferric yeast cytochrome c peroxidase in the presence of different anions may assume a number of forms which differ in optical spectra and chemical properties. In solutions whose only anion is acetate, two spectral forms are present together in an equilibrium. Each of these spectral species is believed to bear bound acetate anion. A form characterized by an intense absorption maximum at 620 nm is unreactive enzymatically and does not react with hydrogen peroxide or with dithionite. A form characterized by a less intense absorption near 645 nm is enzymatically and chemically reactive. Increasing temperature and increasing pH displace the equilibrium toward the 645 nm form. Increasing cytochrome c peroxidase concentration favors the 620 nm form. In kinetic experiments in which the 645 nm form is removed by rapid reaction with H2O2 or dithionite, the 620 nm form is converted in a first order reaction (k = 0.36 s-1, 15 degrees C) to the 645 nm form. In solutions whose sole anion is phosphate a 645 nm form is the only demonstrable spectral species. The enzymatic activity and rates of chemical reaction of 645 nm spectral forms occurring in acetate and in phosphate buffers are the same.", "contents": "Cytochrome c peroxidase. Interconversion of chemically and enzymatically reactive and unreactive forms of the ferric protein. Ferric yeast cytochrome c peroxidase in the presence of different anions may assume a number of forms which differ in optical spectra and chemical properties. In solutions whose only anion is acetate, two spectral forms are present together in an equilibrium. Each of these spectral species is believed to bear bound acetate anion. A form characterized by an intense absorption maximum at 620 nm is unreactive enzymatically and does not react with hydrogen peroxide or with dithionite. A form characterized by a less intense absorption near 645 nm is enzymatically and chemically reactive. Increasing temperature and increasing pH displace the equilibrium toward the 645 nm form. Increasing cytochrome c peroxidase concentration favors the 620 nm form. In kinetic experiments in which the 645 nm form is removed by rapid reaction with H2O2 or dithionite, the 620 nm form is converted in a first order reaction (k = 0.36 s-1, 15 degrees C) to the 645 nm form. In solutions whose sole anion is phosphate a 645 nm form is the only demonstrable spectral species. The enzymatic activity and rates of chemical reaction of 645 nm spectral forms occurring in acetate and in phosphate buffers are the same."}
{"id": "PMID:221488", "title": "Two molecular forms of (Na+ + K+)-stimulated ATPase in brain. Separation, and difference in affinity for strophanthidin.", "content": "The brain contains two distinct molecular forms of the (Na,K)-ATPase (sodium and potassium ion-stimulated adenosine triphosphatase). They can be resolved by gel electrophoresis in sodium dodecyl sulfate, and can be identified by sodium-dependent, potassium-sensitive phosphorylation by [gamma-32P]ATP. They are present in the brain of every animal species examined, while only one molecular form is detected in the other organs examined. They are located in different kinds of cells within the brain, and can be physically separated while fully active by gentle tissue fractionation procedures. One is the only (Na,K)-ATPase of brain non-neuronal cells (astrocytes), while the other is the only (Na,K)-ATPase of axolemma (plasma membrane of myelinated axons). They differ in at least one kinetic parameter: the affinity for the specific inhibitor strophanthidin. They have similar one-dimensional peptide maps, but differ in their sensitivity to digestion by trypsin and in the number or reactivity of sulfhydryl groups. It is anticipated that they will be found to play functionally different roles in the complex ion transport mechanisms of the brain.", "contents": "Two molecular forms of (Na+ + K+)-stimulated ATPase in brain. Separation, and difference in affinity for strophanthidin. The brain contains two distinct molecular forms of the (Na,K)-ATPase (sodium and potassium ion-stimulated adenosine triphosphatase). They can be resolved by gel electrophoresis in sodium dodecyl sulfate, and can be identified by sodium-dependent, potassium-sensitive phosphorylation by [gamma-32P]ATP. They are present in the brain of every animal species examined, while only one molecular form is detected in the other organs examined. They are located in different kinds of cells within the brain, and can be physically separated while fully active by gentle tissue fractionation procedures. One is the only (Na,K)-ATPase of brain non-neuronal cells (astrocytes), while the other is the only (Na,K)-ATPase of axolemma (plasma membrane of myelinated axons). They differ in at least one kinetic parameter: the affinity for the specific inhibitor strophanthidin. They have similar one-dimensional peptide maps, but differ in their sensitivity to digestion by trypsin and in the number or reactivity of sulfhydryl groups. It is anticipated that they will be found to play functionally different roles in the complex ion transport mechanisms of the brain."}
{"id": "PMID:221490", "title": "The role of oxygen in the biosynthesis of cytochrome c oxidase of yeast mitochondria.", "content": "The formation of cytochrome c oxidase in yeast is dependent on oxygen. In order to examine the oxygen-dependent formation of the active enzyme, the effect of oxygen on the synthesis and the assembly of cytochrome c oxidase subunits was studied. Pulse-labeling experiments revealed that oxygen has no significant immediate effect on the synthesis of the three mitochondrially made subunits I to III; however, its presence causes subunits I and II to form a complex with the cytoplasmically made subunits VI and VII. This \"assembly-inducing\" effect can be demonstrated with intact yeast cells as well as with isolated mitochondria. It is independent of cytoplasmic or mitochondrial protein synthesis. After anaerobic growth for 10 or more generations, the intracellular concentrations of individual cytochrome c oxidase subunits drop 10- to 100-fold. Most of these residual subunits are not assembled within a functional cytochrome c oxidase molecule.", "contents": "The role of oxygen in the biosynthesis of cytochrome c oxidase of yeast mitochondria. The formation of cytochrome c oxidase in yeast is dependent on oxygen. In order to examine the oxygen-dependent formation of the active enzyme, the effect of oxygen on the synthesis and the assembly of cytochrome c oxidase subunits was studied. Pulse-labeling experiments revealed that oxygen has no significant immediate effect on the synthesis of the three mitochondrially made subunits I to III; however, its presence causes subunits I and II to form a complex with the cytoplasmically made subunits VI and VII. This \"assembly-inducing\" effect can be demonstrated with intact yeast cells as well as with isolated mitochondria. It is independent of cytoplasmic or mitochondrial protein synthesis. After anaerobic growth for 10 or more generations, the intracellular concentrations of individual cytochrome c oxidase subunits drop 10- to 100-fold. Most of these residual subunits are not assembled within a functional cytochrome c oxidase molecule."}
{"id": "PMID:221492", "title": "Sequence of two phosphorylated sites in the catalytic subunit of bovine cardiac muscle adenosine 3':5'-monophosphate-dependent protein kinase.", "content": "The sequences of two phosphopeptides isolated from the catalytic subunit of bovine cardiac muscle cAMP-dependent protein kinase (type II) and from two of its cyanogen bromide fragments, have been determined. One phosphorylation site is a threonyl residue located approximately 180 residues from the blocked NH2 terminus. Its sequence is: -Gly-Arg-Thr-Trp-Thr(P)-Leu-Cys- and includes one of the three sulfhydryl groups present in the molecule. The second phosphorylated site within the sequence: -Val-Ser(P)-Ile-Asn- is located towards the carboxyl end of the protein where the other 2 cysteinyl residues also reside. The finding that phosphorylation of the catalytic subunit occurs on two discrete sites rather than at random suggests that it might be of physiological importance, e.g. in the regulation of enzyme activity.", "contents": "Sequence of two phosphorylated sites in the catalytic subunit of bovine cardiac muscle adenosine 3':5'-monophosphate-dependent protein kinase. The sequences of two phosphopeptides isolated from the catalytic subunit of bovine cardiac muscle cAMP-dependent protein kinase (type II) and from two of its cyanogen bromide fragments, have been determined. One phosphorylation site is a threonyl residue located approximately 180 residues from the blocked NH2 terminus. Its sequence is: -Gly-Arg-Thr-Trp-Thr(P)-Leu-Cys- and includes one of the three sulfhydryl groups present in the molecule. The second phosphorylated site within the sequence: -Val-Ser(P)-Ile-Asn- is located towards the carboxyl end of the protein where the other 2 cysteinyl residues also reside. The finding that phosphorylation of the catalytic subunit occurs on two discrete sites rather than at random suggests that it might be of physiological importance, e.g. in the regulation of enzyme activity."}
{"id": "PMID:221493", "title": "Synthesis of a new 8-spin-labeled analog of adenosine 5'-phosphate and its interaction with AMP nucleosidase.", "content": "The synthesis of a new 8-spin-labeled analog of AMP, 8-[[[(2,2,5,5-tetramethyl-1-oxy-3-pyrrolidinyl)carbamoyl]methyl]thio]adenosine 5'-phosphate (8-slAMP), is described. The procedure is facile and results in high yields. 8-slAMP is a competitive inhibitor of AMP nucleosidase with a Ki of 19 microM as compared to a Km of 100 microM for AMP. The analog is not a substrate for the enzyme and does not displace MgATP2- from the allosteric sites under the usual assay conditions. The EPR spectrum of the bound spin probe reveals a highly immobilized nitroxide group. Binding studies with 8-slAMP at 8 degrees C indicate three independent binding sites (Kd = 1.4 microM) per molecule of enzyme (Mr = 320,000). These properties make 8-slAMP a good spin probe for AMP nucleosidase. The analog may also be useful for other proteins known or suspected of binding AMP analogs in a syn conformation.", "contents": "Synthesis of a new 8-spin-labeled analog of adenosine 5'-phosphate and its interaction with AMP nucleosidase. The synthesis of a new 8-spin-labeled analog of AMP, 8-[[[(2,2,5,5-tetramethyl-1-oxy-3-pyrrolidinyl)carbamoyl]methyl]thio]adenosine 5'-phosphate (8-slAMP), is described. The procedure is facile and results in high yields. 8-slAMP is a competitive inhibitor of AMP nucleosidase with a Ki of 19 microM as compared to a Km of 100 microM for AMP. The analog is not a substrate for the enzyme and does not displace MgATP2- from the allosteric sites under the usual assay conditions. The EPR spectrum of the bound spin probe reveals a highly immobilized nitroxide group. Binding studies with 8-slAMP at 8 degrees C indicate three independent binding sites (Kd = 1.4 microM) per molecule of enzyme (Mr = 320,000). These properties make 8-slAMP a good spin probe for AMP nucleosidase. The analog may also be useful for other proteins known or suspected of binding AMP analogs in a syn conformation."}
{"id": "PMID:221495", "title": "NAD-dependent ADP-ribosylation of arginine and proteins by Escherichia coli heat-labile enterotoxin.", "content": "Escherichia coli heat-labile enterotoxin (labile toxin, LT) catalyzed the hydrolysis of NAD to ADP-ribose and nicotinamide and the ADP-ribosylation of arginine (Moss, J., and Richardson, S.H. (1978) J. Clin. Invest. 62, 281-285). Analysis of the product of the ADP-ribosylation of arginine by nuclear magnetic resonance spectroscopy indicated that the reaction was stereospecific and resulted in the formation of alpha-ADP-ribosyl-L-arginine. This reaction product rapidly anomerized to yield a mixture of the alpha and beta forms. In the presence of [adenine-U-14C]NAD, E. coli enterotoxin catalyzed the transfer of the radiolabel to proteins; the ADP-ribosylation of proteins was inhibited by arginine methyl ester, an alternative substrate. Digestion of the 14C-protein with snake venom phosphodiesterase released predominantly 5'-AMP. No product was obtained with a mobility similar to that of 2'-(5''-phosphoribosyl)-5'-AMP. This result is consistent with the covalent attachment by the enterotoxin of ADP-ribose rather than poly(ADP-ribose) to protein. Thus, LT is catalytically equivalent to choleragen, an enterotoxin of Vibrio cholerae, and activates adenylate cyclase through a similar stereospecific ADP-ribosylation reaction.", "contents": "NAD-dependent ADP-ribosylation of arginine and proteins by Escherichia coli heat-labile enterotoxin. Escherichia coli heat-labile enterotoxin (labile toxin, LT) catalyzed the hydrolysis of NAD to ADP-ribose and nicotinamide and the ADP-ribosylation of arginine (Moss, J., and Richardson, S.H. (1978) J. Clin. Invest. 62, 281-285). Analysis of the product of the ADP-ribosylation of arginine by nuclear magnetic resonance spectroscopy indicated that the reaction was stereospecific and resulted in the formation of alpha-ADP-ribosyl-L-arginine. This reaction product rapidly anomerized to yield a mixture of the alpha and beta forms. In the presence of [adenine-U-14C]NAD, E. coli enterotoxin catalyzed the transfer of the radiolabel to proteins; the ADP-ribosylation of proteins was inhibited by arginine methyl ester, an alternative substrate. Digestion of the 14C-protein with snake venom phosphodiesterase released predominantly 5'-AMP. No product was obtained with a mobility similar to that of 2'-(5''-phosphoribosyl)-5'-AMP. This result is consistent with the covalent attachment by the enterotoxin of ADP-ribose rather than poly(ADP-ribose) to protein. Thus, LT is catalytically equivalent to choleragen, an enterotoxin of Vibrio cholerae, and activates adenylate cyclase through a similar stereospecific ADP-ribosylation reaction."}
{"id": "PMID:221496", "title": "Total assignments, including four aromatic residues, and sequence confirmation of the decapeptide tyrocidine A using difference double resonance. Qualitative nuclear overhauser effect criteria for beta turn and antiparallel beta-pleated sheet conformations.", "content": "The complete assignments of all the proton magnetic resonance signals from each NH-CalphaH-CbetaH2 moiety in a complex peptide containing several residues of the same type has not yet been achieved without specific or stereospecific isotopic enrichment. We report the sequencing and proton magnetic resonance spectral assignments, including those of 4 aromatic residues, of tyrocidine A, an analog of the decapeptide gramicidin S. Two complementary methods, proton-proton nuclear Overhauser enhancements and scalar decoupling, evaluated by two distinct forms of difference double resonance, were used. All chemical shifts, scalar coupling constants, and [1H:1H] nuclear Overhauser enhancements for the backbone protons are reported. The [1H:1H] nuclear Overhauser enhancements are consistent with tyrocidine A possessing a beta-I turn/beta-II' turn/antiparallel beta-pleated sheet conformation. In addition to the previously proposed nuclear Overhauser enhancement criteria for beta turns and antiparallel beta sheets, another criterion for identifying the antiparallel beta sheet is demonstrated; namely, the nuclear Overhauser enhancement between 2 CalphaH protons of the central resisdues, in this case the Phe7CalphaH and Orn2CalphaH.", "contents": "Total assignments, including four aromatic residues, and sequence confirmation of the decapeptide tyrocidine A using difference double resonance. Qualitative nuclear overhauser effect criteria for beta turn and antiparallel beta-pleated sheet conformations. The complete assignments of all the proton magnetic resonance signals from each NH-CalphaH-CbetaH2 moiety in a complex peptide containing several residues of the same type has not yet been achieved without specific or stereospecific isotopic enrichment. We report the sequencing and proton magnetic resonance spectral assignments, including those of 4 aromatic residues, of tyrocidine A, an analog of the decapeptide gramicidin S. Two complementary methods, proton-proton nuclear Overhauser enhancements and scalar decoupling, evaluated by two distinct forms of difference double resonance, were used. All chemical shifts, scalar coupling constants, and [1H:1H] nuclear Overhauser enhancements for the backbone protons are reported. The [1H:1H] nuclear Overhauser enhancements are consistent with tyrocidine A possessing a beta-I turn/beta-II' turn/antiparallel beta-pleated sheet conformation. In addition to the previously proposed nuclear Overhauser enhancement criteria for beta turns and antiparallel beta sheets, another criterion for identifying the antiparallel beta sheet is demonstrated; namely, the nuclear Overhauser enhancement between 2 CalphaH protons of the central resisdues, in this case the Phe7CalphaH and Orn2CalphaH."}
{"id": "PMID:221497", "title": "Effect of plasma membranes on solute transport in 3T3 cells.", "content": "Sparse cultures of Swiss 3T3 cells are arrested early in the G1 phase of growth by the addition of a plasma membrane fraction obtained from confluent 3T3 cells. We have examined whether the changes in solute transport which are usually associated with cessation of growth at confluency also take place when cell growth is arrested by the addition of plasma membranes. We find that the rate of uptake of alpha-aminoisobutyric acid and uridine is decreased after the addition of plasma membranes to 3T3 cells, but the rate of uptake of 2-deoxyglucose and phosphate is not. We conclude from these observations that uptake of uridine and alpha-aminoisobutyric acid are related to contact inhibition of growth, while the decline in the rate of uptake of 2-deoxyglucose and phosphate observed at high cell density must be due to changes other than cell to cell contact.", "contents": "Effect of plasma membranes on solute transport in 3T3 cells. Sparse cultures of Swiss 3T3 cells are arrested early in the G1 phase of growth by the addition of a plasma membrane fraction obtained from confluent 3T3 cells. We have examined whether the changes in solute transport which are usually associated with cessation of growth at confluency also take place when cell growth is arrested by the addition of plasma membranes. We find that the rate of uptake of alpha-aminoisobutyric acid and uridine is decreased after the addition of plasma membranes to 3T3 cells, but the rate of uptake of 2-deoxyglucose and phosphate is not. We conclude from these observations that uptake of uridine and alpha-aminoisobutyric acid are related to contact inhibition of growth, while the decline in the rate of uptake of 2-deoxyglucose and phosphate observed at high cell density must be due to changes other than cell to cell contact."}
{"id": "PMID:221499", "title": "T4 gene 32 protein trypsin-generated fragments. Fluorescence measurement of DNA-binding parameters.", "content": "The intrinsic fluorescence of the T4 helix-destabilizing protein specified by gene 32 (32P) is not altered by the proteolytic removal of either the 6200-dalton COOH-terminal \"A\" region (32P*-A) or both the A and the 2300-dalton NH2-terminal \"B\" region (32P*-(A + B)). The intrinsic fluorescence of 32P, 32P*-A, and 32P*-(A + B) is decreased 23% by the addition of d(pT)8 and 34% by the addition of poly(dT). Saturation binding curves of the percentage of change in protein fluorescence as a function of nucleotide concentration show that the intact 32P as well as the two proteolysis-generated fragments all have association constants of approximately 10(6) M-1 for d(pT)8. This demonstrates that the DNA binding site is not contained within either the A or B regions of 32P. Both 32P and 32P*-A bind cooperatively to poly(dT) as evidenced by a 400- to 1000-fold increase in association constant for poly(dT) compared to d(pT)8. Since within the limits of our measurements 32P and 32P*-A bind equally well to poly(dT) (Kassoc approximately 5 . 10(8) M-1), the enhanced helix-destabilizing properties previously reported for 32P*-A cannot be accounted for by a significant increase in binding affinity of 32P*-A for single-stranded DNA. The binding constant for the 32P*-(A + B):poly(dT) complex is only 3-fold higher than that for the 32P*-(A + B):d(pT)8 complex, which confirms our proposal that the B region is essential for cooperative 32P:32P protein interactions.", "contents": "T4 gene 32 protein trypsin-generated fragments. Fluorescence measurement of DNA-binding parameters. The intrinsic fluorescence of the T4 helix-destabilizing protein specified by gene 32 (32P) is not altered by the proteolytic removal of either the 6200-dalton COOH-terminal \"A\" region (32P*-A) or both the A and the 2300-dalton NH2-terminal \"B\" region (32P*-(A + B)). The intrinsic fluorescence of 32P, 32P*-A, and 32P*-(A + B) is decreased 23% by the addition of d(pT)8 and 34% by the addition of poly(dT). Saturation binding curves of the percentage of change in protein fluorescence as a function of nucleotide concentration show that the intact 32P as well as the two proteolysis-generated fragments all have association constants of approximately 10(6) M-1 for d(pT)8. This demonstrates that the DNA binding site is not contained within either the A or B regions of 32P. Both 32P and 32P*-A bind cooperatively to poly(dT) as evidenced by a 400- to 1000-fold increase in association constant for poly(dT) compared to d(pT)8. Since within the limits of our measurements 32P and 32P*-A bind equally well to poly(dT) (Kassoc approximately 5 . 10(8) M-1), the enhanced helix-destabilizing properties previously reported for 32P*-A cannot be accounted for by a significant increase in binding affinity of 32P*-A for single-stranded DNA. The binding constant for the 32P*-(A + B):poly(dT) complex is only 3-fold higher than that for the 32P*-(A + B):d(pT)8 complex, which confirms our proposal that the B region is essential for cooperative 32P:32P protein interactions."}
{"id": "PMID:221500", "title": "Brain pyridoxal kinase. Purification, substrate specificities, and sensitized photodestruction of an essential histidine.", "content": "Pyridoxal kinase has been purified 2,000-fold from pig brain. The enzyme preparation migrates as a single protein and activity band on analytical gel electrophoresis. Pyridoxal kinase, 60,000 molecular weight, catalyzes the phosphorylation of pyridoxal (Km = 2.5 x 10(-5) M) and pyridoxine (Km = 1.7 x 10(-5) M). Pyridoxamine is not a substrate of the purified kinase. Irradiation of the kinase in the presence of riboflavin leads to irreversible loss of catalytic activity. Riboflavin binds to the kinase with a KD = 5 microM as shown by fluorometric titrations. Singlet excited oxygen, generated by energy transfer from the lowest triplet of riboflavin to oxygen, acts as the oxidizing agent of approximately one histidine residue per mol of enzyme. The amino acid residues tyrosine, tryptophan, and cysteine are not photooxidized by the sensitizer bound to the enzyme. It is postulated that histidine is involved in the binding of the substrate ATP to the catalytic site of pyridoxal kinase.", "contents": "Brain pyridoxal kinase. Purification, substrate specificities, and sensitized photodestruction of an essential histidine. Pyridoxal kinase has been purified 2,000-fold from pig brain. The enzyme preparation migrates as a single protein and activity band on analytical gel electrophoresis. Pyridoxal kinase, 60,000 molecular weight, catalyzes the phosphorylation of pyridoxal (Km = 2.5 x 10(-5) M) and pyridoxine (Km = 1.7 x 10(-5) M). Pyridoxamine is not a substrate of the purified kinase. Irradiation of the kinase in the presence of riboflavin leads to irreversible loss of catalytic activity. Riboflavin binds to the kinase with a KD = 5 microM as shown by fluorometric titrations. Singlet excited oxygen, generated by energy transfer from the lowest triplet of riboflavin to oxygen, acts as the oxidizing agent of approximately one histidine residue per mol of enzyme. The amino acid residues tyrosine, tryptophan, and cysteine are not photooxidized by the sensitizer bound to the enzyme. It is postulated that histidine is involved in the binding of the substrate ATP to the catalytic site of pyridoxal kinase."}
{"id": "PMID:221504", "title": "Adeno-associated virus DNA replication complexes in herpes simplex virus or adenovirus-infected cells.", "content": "A complex which is active in in vitro synthesis of adeno-associated virus (AAV) DNA was solubilized from Vero cells that were co-infected with AAV and either adenovirus (Ad5) or a herpes simplex virus type 1 (HSV-1) as the helper virus. The complexes from the Ad5 and HSV-1-infected cells sedimented at 23 S and 28 S, respectively. The optimal conditions for in vitro DNA synthesis for the two types of complex using the endogenous AAV template and the endogenous DNA polymerase, differed with respect to the effect of KCl and K2SO4 concentration. In addition the complex from HSV-1-infected cells, but not that from Ad5-infected cells, was inhibited by phosphonoacetic acid. Thus, the two complexes appear to contain different DNA polymerase activities. This was verified by phosphocellulose chromatography of the DNA polymerases solubilized from the isolated complexes. The major activity in the complex from HSV-1 infected cells was the HSV-induced DNA polymerase with lesser amounts of cellular DNA polymerase alpha and gamma or both. The complex from the Ad5-infected cells contained mainly a cellular DNA polymerase gamma.", "contents": "Adeno-associated virus DNA replication complexes in herpes simplex virus or adenovirus-infected cells. A complex which is active in in vitro synthesis of adeno-associated virus (AAV) DNA was solubilized from Vero cells that were co-infected with AAV and either adenovirus (Ad5) or a herpes simplex virus type 1 (HSV-1) as the helper virus. The complexes from the Ad5 and HSV-1-infected cells sedimented at 23 S and 28 S, respectively. The optimal conditions for in vitro DNA synthesis for the two types of complex using the endogenous AAV template and the endogenous DNA polymerase, differed with respect to the effect of KCl and K2SO4 concentration. In addition the complex from HSV-1-infected cells, but not that from Ad5-infected cells, was inhibited by phosphonoacetic acid. Thus, the two complexes appear to contain different DNA polymerase activities. This was verified by phosphocellulose chromatography of the DNA polymerases solubilized from the isolated complexes. The major activity in the complex from HSV-1 infected cells was the HSV-induced DNA polymerase with lesser amounts of cellular DNA polymerase alpha and gamma or both. The complex from the Ad5-infected cells contained mainly a cellular DNA polymerase gamma."}
{"id": "PMID:221506", "title": "Acetate kinase from Veillonella alcalescens. Regulation by succinate and substrates.", "content": "The kinetic properties of acetate kinase from Veillonella alcalescens were investigated. In the presence of high concentrations of nucleotide both forward and reverse reactions were observed. In the presence of succinate the degree of cooperativity between subunits of the homodimer decreased, i.e. the Hill coefficient, n, decreased from 2.5 to 1.4 for acetyl phosphate in the presence of succinate. At low substrate concentrations hyperbolic kinetic data were observed with succinate. We have proposed a modified version of the concerted symmetry model to describe the kinetics observed with this enzyme. The primary differentiating feature of the proposed model is the requirement for activator ligand binding for catalysis. In the absence of succinate, the substrate (acetate or acetyl phosphate) also functions as an activating ligand.", "contents": "Acetate kinase from Veillonella alcalescens. Regulation by succinate and substrates. The kinetic properties of acetate kinase from Veillonella alcalescens were investigated. In the presence of high concentrations of nucleotide both forward and reverse reactions were observed. In the presence of succinate the degree of cooperativity between subunits of the homodimer decreased, i.e. the Hill coefficient, n, decreased from 2.5 to 1.4 for acetyl phosphate in the presence of succinate. At low substrate concentrations hyperbolic kinetic data were observed with succinate. We have proposed a modified version of the concerted symmetry model to describe the kinetics observed with this enzyme. The primary differentiating feature of the proposed model is the requirement for activator ligand binding for catalysis. In the absence of succinate, the substrate (acetate or acetyl phosphate) also functions as an activating ligand."}
{"id": "PMID:221511", "title": "Purification and partial characterization of a nonprimate growth hormone receptor.", "content": "Pregnant rabbit liver membranes have been shown to possess two types of receptors by displacement analysis, a growth hormone (GH) receptor which binds bovine growth hormone with an affinity constant (KA) of 3 x 10(9) M-1 and ovine prolactin with a KA of 3 x 10(8) M-1, and a prolactin (Prl)-specific receptor which binds ovine prolactin with a KA of 5 x 10(9) M-1. The prolactin-specific receptor when solubilized with Triton exhibits a 4-fold increase in the its KA while the KA of the growth hormone receptor decreases slightly to 2 x 10(9) M-1 after solubilization. The 10-fold difference in affinity which results has been exploited to facilitate the separation of these two receptors by differential affinity chromatography on human growth hormone (hGH) affinity gels. The growth hormone receptor is eluted from the gel with 4 M urea while 5 M MgCl2 is required to elute the prolactin receptor. Conditions of affinity chromatography have been optimized, and further purification of the GH receptor by preparative isoelectric focusing and Sepharose 6B gel filtration resulted in a more than 8000-fold purification of the receptor. This material had a Stokes radius of 62 A, consistent with a molecular weight of 300,000 and gave one main band (75,000 to 80,000) and two minor bands on sodium dodecyl sulfate (SDS) polyacrylamide gels, which could be interpreted as indicating a tetrameric receptor. The GH receptor was shown to be a sialoglycoprotein (or closely associated with sialoglycoprotein) by analytical isoelectric focusing with an isoelectric point of 4.6. Specificity studies with the highly purified receptor confirmed the initial hypothesis that this receptor is capable of binding bovine growth hormone (bGH) with high affinity and ovine prolactin (oPrl) with low affinity, in contrast to the prolactin-specific receptor.", "contents": "Purification and partial characterization of a nonprimate growth hormone receptor. Pregnant rabbit liver membranes have been shown to possess two types of receptors by displacement analysis, a growth hormone (GH) receptor which binds bovine growth hormone with an affinity constant (KA) of 3 x 10(9) M-1 and ovine prolactin with a KA of 3 x 10(8) M-1, and a prolactin (Prl)-specific receptor which binds ovine prolactin with a KA of 5 x 10(9) M-1. The prolactin-specific receptor when solubilized with Triton exhibits a 4-fold increase in the its KA while the KA of the growth hormone receptor decreases slightly to 2 x 10(9) M-1 after solubilization. The 10-fold difference in affinity which results has been exploited to facilitate the separation of these two receptors by differential affinity chromatography on human growth hormone (hGH) affinity gels. The growth hormone receptor is eluted from the gel with 4 M urea while 5 M MgCl2 is required to elute the prolactin receptor. Conditions of affinity chromatography have been optimized, and further purification of the GH receptor by preparative isoelectric focusing and Sepharose 6B gel filtration resulted in a more than 8000-fold purification of the receptor. This material had a Stokes radius of 62 A, consistent with a molecular weight of 300,000 and gave one main band (75,000 to 80,000) and two minor bands on sodium dodecyl sulfate (SDS) polyacrylamide gels, which could be interpreted as indicating a tetrameric receptor. The GH receptor was shown to be a sialoglycoprotein (or closely associated with sialoglycoprotein) by analytical isoelectric focusing with an isoelectric point of 4.6. Specificity studies with the highly purified receptor confirmed the initial hypothesis that this receptor is capable of binding bovine growth hormone (bGH) with high affinity and ovine prolactin (oPrl) with low affinity, in contrast to the prolactin-specific receptor."}
{"id": "PMID:221512", "title": "Leydig cell hypoplasia: a cause of male pseudohermaphroditism.", "content": "A patient with male pseudohermaphroditism is presented whose testicular biopsy showed marked paucity of the Leydig cell populations to which is attributed testosterone deficiency and impaired spermatogenesis.", "contents": "Leydig cell hypoplasia: a cause of male pseudohermaphroditism. A patient with male pseudohermaphroditism is presented whose testicular biopsy showed marked paucity of the Leydig cell populations to which is attributed testosterone deficiency and impaired spermatogenesis."}
{"id": "PMID:221513", "title": "Selective hypopituitarism with severe hyponatremia and secondary hyporeninism.", "content": "A female patient presenting clinically a severe hyponatremia was found to have a selective hypopituitarism with predominant ACTH and partial FSH, LH, and GH deficiency as well as a suppression of plasma renin activity and aldosterone. The adrenal cortex responded well in cortisol increase to ACTH infusion and in plasma aldosterone increase to angiotensin II infusion. The patient had pressor hyperreactivity to angiotensin II. The hyponatremia was caused by a negative sodium balance induced by excessive urinary loss which remained unaffected by mineralocorticoid treatment. Substitution doses of cortisol, however, corrected the disturbance with an increase in plasma renin activity and improvement in the sodium balance. The data are interpreted as indicating a direct or indirect regulatory (permissive?) effect of low doses of cortisol on plasma renin activity correcting the underlying disturbance--the secondary hyporeninism.", "contents": "Selective hypopituitarism with severe hyponatremia and secondary hyporeninism. A female patient presenting clinically a severe hyponatremia was found to have a selective hypopituitarism with predominant ACTH and partial FSH, LH, and GH deficiency as well as a suppression of plasma renin activity and aldosterone. The adrenal cortex responded well in cortisol increase to ACTH infusion and in plasma aldosterone increase to angiotensin II infusion. The patient had pressor hyperreactivity to angiotensin II. The hyponatremia was caused by a negative sodium balance induced by excessive urinary loss which remained unaffected by mineralocorticoid treatment. Substitution doses of cortisol, however, corrected the disturbance with an increase in plasma renin activity and improvement in the sodium balance. The data are interpreted as indicating a direct or indirect regulatory (permissive?) effect of low doses of cortisol on plasma renin activity correcting the underlying disturbance--the secondary hyporeninism."}
{"id": "PMID:221515", "title": "Suppression of plasma catecholamines and flushing by clonidine in man.", "content": "Administration of the anti-hypertensive agent clonidine as a single (0.5 mg) oral dose or as multiple doses (0.2-0.4 mg/day for 4 days) markedly reduced plasma catecholamines (decrement = 81 +/- 3% and 68 +/- 5%, respectively; X +/- SE, % of basal; both P less than 0.001) in normal male volunteers. Five patients with various metabolic disorders showed similar responses. The absolute decrements in plasma catecholamines correlated significantly with basal catecholamine levels (P less than 0.001). Clonidine-induced decrements in mean arterial blood pressure correlated significantly with decrements in plasma catecholamines (P less than 0.001). The clonidine effect upon catecholamine levels was reversed by phentolamine (clonidine = -68 +/- 5%; clonidine with phentolamine = -1 +/- 16%). The decrements in catecholamines induced by clonidine in normal subjects were associated with increased sensitivity to the pressor effect of infusion of exogenous norepinephrine. In an analogous fashion flushing associated with endogenous adrenergic discharge was blocked by clonidine, whereas that due to exogenous catecholamines was intensified. These data are compatible with data in experimental animals suggesting that clonidine acts at least in part by interaction with a central alpha adrenergic receptor.", "contents": "Suppression of plasma catecholamines and flushing by clonidine in man. Administration of the anti-hypertensive agent clonidine as a single (0.5 mg) oral dose or as multiple doses (0.2-0.4 mg/day for 4 days) markedly reduced plasma catecholamines (decrement = 81 +/- 3% and 68 +/- 5%, respectively; X +/- SE, % of basal; both P less than 0.001) in normal male volunteers. Five patients with various metabolic disorders showed similar responses. The absolute decrements in plasma catecholamines correlated significantly with basal catecholamine levels (P less than 0.001). Clonidine-induced decrements in mean arterial blood pressure correlated significantly with decrements in plasma catecholamines (P less than 0.001). The clonidine effect upon catecholamine levels was reversed by phentolamine (clonidine = -68 +/- 5%; clonidine with phentolamine = -1 +/- 16%). The decrements in catecholamines induced by clonidine in normal subjects were associated with increased sensitivity to the pressor effect of infusion of exogenous norepinephrine. In an analogous fashion flushing associated with endogenous adrenergic discharge was blocked by clonidine, whereas that due to exogenous catecholamines was intensified. These data are compatible with data in experimental animals suggesting that clonidine acts at least in part by interaction with a central alpha adrenergic receptor."}
{"id": "PMID:221517", "title": "DDAVP (1-desamino-8-D-arginine-vasopressin) treatment of central diabetes insipidus--mechanism of prolonged antidiuresis.", "content": "DDAVP, 1-desamino-8-D-arginine-vasopressin, is a synthetic analog of arginine vasopressin which produces prolonged antidiuresis after intranasal administration to patients with complete central diabetes insipidus. We have studied the mechanism of the prolonged antidiuretic effect by specific radioimmunossay of DDAVP in plasma of patients and by in vitro studies on the adenylate cyclase-cylic AMP system of the rat outer renal medulla. When DDAVP was administredd to patients, all responded, but the duration of response among patients varied from 5-21 h. The peak level of DDAVP in plasma was achieved up to 4 h after administration indicating a slow absorption from the nasal mucosa. The disappearance time of DDAVP from plasma correlated significantly with the duration of antidiuresis, P less than 0.001. On a molar basis DDAVP was 3-fold greater than AVP in its stimulation of outer medullary adenylate cyclase activity and 10-fold greater than AVP in its stimulation of cyclic AMP content. The prolonged antidiuresis of intranasally administered DDAVP is due to slow absorption, presistence in plasma, and enchanced effect on the kidney.", "contents": "DDAVP (1-desamino-8-D-arginine-vasopressin) treatment of central diabetes insipidus--mechanism of prolonged antidiuresis. DDAVP, 1-desamino-8-D-arginine-vasopressin, is a synthetic analog of arginine vasopressin which produces prolonged antidiuresis after intranasal administration to patients with complete central diabetes insipidus. We have studied the mechanism of the prolonged antidiuretic effect by specific radioimmunossay of DDAVP in plasma of patients and by in vitro studies on the adenylate cyclase-cylic AMP system of the rat outer renal medulla. When DDAVP was administredd to patients, all responded, but the duration of response among patients varied from 5-21 h. The peak level of DDAVP in plasma was achieved up to 4 h after administration indicating a slow absorption from the nasal mucosa. The disappearance time of DDAVP from plasma correlated significantly with the duration of antidiuresis, P less than 0.001. On a molar basis DDAVP was 3-fold greater than AVP in its stimulation of outer medullary adenylate cyclase activity and 10-fold greater than AVP in its stimulation of cyclic AMP content. The prolonged antidiuresis of intranasally administered DDAVP is due to slow absorption, presistence in plasma, and enchanced effect on the kidney."}
{"id": "PMID:221518", "title": "Prolonged infusions of Ile5-angiotensin-II in sodium replete and deplete man: effects on aldosterone, ACTH, cortisol, blood pressure, and electrolyte balance.", "content": "Angiotensin II (Ile5) was infused for 72 h into 4 sodium replete (3 ng/kg/min) and 8 sodium deplete (3 or 6 ng/kg/min) healthy young men after appropriate control periods, and the effects on aldosterone secretion, plasma cortisol, ACTH, renin activity, plasma and urinary electrolytes, and blood pressure were assessed. Sustained contrived elevation of plasma angiotensin II levels in sodium replete subjects to the range of moderate sodium depletion led to a sustained increase in plasma and urinary aldosterone levels, which further and significantly increased between the 1st and 2nd days of angiotensin II infusion, when gross sodium retention during infusion was prevented. This additional increase may be explained as the expression of a \"trophic\" effect of angiotension II on the zona glomerulosa. In the sodium deplete state, the absolute increment of aldosterone secretion for a given elevation of angiotensin II levels diring infusion was larger than in sodium replete subjects. This confirms the conclusions from previous short-term angiotensin II infusion experiments that sodium deficiency sensitizes the zona glomerulosa against angiotensin II. The \"trophic\" effect of angiotensin II on the adrenal gland seems to be one mechanism by which the sensitization is brought about, but insufficient for its full explanation. Since plasma ACTH and cortisol, plasma sodium and potassium concentrations, and potassium blance did not change significantly across sodium depletion or angiotensin II infusion, the mechanism of sensitization awaits its full elucidation. The effect of angiotensin II on blood pressure was blunted by soidum depletion. The opposite shifts in sensitivity against angiotensin II of the zona glomerulosa and of resistance blood vessels with changes in the sodium state seem to be an effective and important means in the regulation of body sodium.", "contents": "Prolonged infusions of Ile5-angiotensin-II in sodium replete and deplete man: effects on aldosterone, ACTH, cortisol, blood pressure, and electrolyte balance. Angiotensin II (Ile5) was infused for 72 h into 4 sodium replete (3 ng/kg/min) and 8 sodium deplete (3 or 6 ng/kg/min) healthy young men after appropriate control periods, and the effects on aldosterone secretion, plasma cortisol, ACTH, renin activity, plasma and urinary electrolytes, and blood pressure were assessed. Sustained contrived elevation of plasma angiotensin II levels in sodium replete subjects to the range of moderate sodium depletion led to a sustained increase in plasma and urinary aldosterone levels, which further and significantly increased between the 1st and 2nd days of angiotensin II infusion, when gross sodium retention during infusion was prevented. This additional increase may be explained as the expression of a \"trophic\" effect of angiotension II on the zona glomerulosa. In the sodium deplete state, the absolute increment of aldosterone secretion for a given elevation of angiotensin II levels diring infusion was larger than in sodium replete subjects. This confirms the conclusions from previous short-term angiotensin II infusion experiments that sodium deficiency sensitizes the zona glomerulosa against angiotensin II. The \"trophic\" effect of angiotensin II on the adrenal gland seems to be one mechanism by which the sensitization is brought about, but insufficient for its full explanation. Since plasma ACTH and cortisol, plasma sodium and potassium concentrations, and potassium blance did not change significantly across sodium depletion or angiotensin II infusion, the mechanism of sensitization awaits its full elucidation. The effect of angiotensin II on blood pressure was blunted by soidum depletion. The opposite shifts in sensitivity against angiotensin II of the zona glomerulosa and of resistance blood vessels with changes in the sodium state seem to be an effective and important means in the regulation of body sodium."}
{"id": "PMID:221519", "title": "Effect of human chorionic gonadotropin on human thyroid tissue in vitro.", "content": "Thyroid stimulating substances other than TSH have been found in certain disease states associated with hyperthyroidism. The thyroid stimulator associated with the thyrotoxicosis of trophoblastic disease is uncertain; however, recent evidence suggests a role for hCG. To explore the thyroid stimulating properties of hCG further, we examined the ability of hCG to displace [1252]TSH from receptors on human thyroid membrane and to generate cyclic-AMP (c-AMP) from human thyroid slices. Human chorionic gonadotropin at a concentration of 40 IU/ml displaced labeled TSH from human thyroid membranes and, at a concentration of 69 IU/ml, hCG caused the generation of c-AMP in thyroid slices. These results suggest that hCG can bind to the TSH receptor on thyroid cells and can stimulate them to produce c-AMP at concentrations of hCG within the range that is found in trophoblastic disease.", "contents": "Effect of human chorionic gonadotropin on human thyroid tissue in vitro. Thyroid stimulating substances other than TSH have been found in certain disease states associated with hyperthyroidism. The thyroid stimulator associated with the thyrotoxicosis of trophoblastic disease is uncertain; however, recent evidence suggests a role for hCG. To explore the thyroid stimulating properties of hCG further, we examined the ability of hCG to displace [1252]TSH from receptors on human thyroid membrane and to generate cyclic-AMP (c-AMP) from human thyroid slices. Human chorionic gonadotropin at a concentration of 40 IU/ml displaced labeled TSH from human thyroid membranes and, at a concentration of 69 IU/ml, hCG caused the generation of c-AMP in thyroid slices. These results suggest that hCG can bind to the TSH receptor on thyroid cells and can stimulate them to produce c-AMP at concentrations of hCG within the range that is found in trophoblastic disease."}
{"id": "PMID:221521", "title": "Effects of the intravenous administration of calcium on nephrogenous cyclic AMP: use as a parathyroid suppression test.", "content": "The question of parathyroid autonomy in primary hyperparathyroidism has been the subject of conflicting immunoassay data. We studied the effects of calcium infusion (12 mg/kg/3h) and calcium injection (3 mg/kg/10 min) on peripheral plasma parathyroid hormone (iPTH) determined with a multivalent antiserum and on the excretion of nephrogenous cyclic AMP in normal subjects and in 7 patients with primary hyperparathyroidism who displayed only mild, intermittent hypercalcemia. In control subjects, calcium administration resulted in small (13-20%) reductions in iPTH, whereas some 4/5 (77-81%) of the nephrogenous cyclic AMP was rapidly and uniformly suppressed. In the patients with primary hyperparathyroidism, both analyses revealed a lack of absolute parathyroid autonomy in response to calcium, with overlapping iPTH responses between a majority of the patients and the control group. In contrast, the nephrogenous cyclic AMP responses provided a clear separation of the 2 groups after both calcium infusion and calcium injection (mean values for both studies, patients: 2.93 nmol/100 ml GF vs. normal sugjects: 0.38 nmol/100 ml GF), and measurements of total cyclic AMP excretion also clearly distinguished the 2 groups. When a sensitive antiserum with predominantly carboxy-terminal reactivity was employed, the iPTH responses to calcium injection provided an improved separation of patients and normal subjects. The data suggest that 1) although parathyroid autonomy is not, in general, a feature of primary hyperparathyroidism, abnormal parathyroid suppressibility is easily demonstrated even in patients with a subtle form of the disorder; 2) the determination of nephrogenous cyclic AMP provides an optimal method for assessing rapid changes in parathyroid function; and 3) the interpretation of iPTH results from such studies is dependent on a number of technological features of the assay employed.", "contents": "Effects of the intravenous administration of calcium on nephrogenous cyclic AMP: use as a parathyroid suppression test. The question of parathyroid autonomy in primary hyperparathyroidism has been the subject of conflicting immunoassay data. We studied the effects of calcium infusion (12 mg/kg/3h) and calcium injection (3 mg/kg/10 min) on peripheral plasma parathyroid hormone (iPTH) determined with a multivalent antiserum and on the excretion of nephrogenous cyclic AMP in normal subjects and in 7 patients with primary hyperparathyroidism who displayed only mild, intermittent hypercalcemia. In control subjects, calcium administration resulted in small (13-20%) reductions in iPTH, whereas some 4/5 (77-81%) of the nephrogenous cyclic AMP was rapidly and uniformly suppressed. In the patients with primary hyperparathyroidism, both analyses revealed a lack of absolute parathyroid autonomy in response to calcium, with overlapping iPTH responses between a majority of the patients and the control group. In contrast, the nephrogenous cyclic AMP responses provided a clear separation of the 2 groups after both calcium infusion and calcium injection (mean values for both studies, patients: 2.93 nmol/100 ml GF vs. normal sugjects: 0.38 nmol/100 ml GF), and measurements of total cyclic AMP excretion also clearly distinguished the 2 groups. When a sensitive antiserum with predominantly carboxy-terminal reactivity was employed, the iPTH responses to calcium injection provided an improved separation of patients and normal subjects. The data suggest that 1) although parathyroid autonomy is not, in general, a feature of primary hyperparathyroidism, abnormal parathyroid suppressibility is easily demonstrated even in patients with a subtle form of the disorder; 2) the determination of nephrogenous cyclic AMP provides an optimal method for assessing rapid changes in parathyroid function; and 3) the interpretation of iPTH results from such studies is dependent on a number of technological features of the assay employed."}
{"id": "PMID:221522", "title": "Thyrotoxicosis: comparison of effects of thyroid ablation and beta-adrenergic blockade on metabolic rate and ventilatory control.", "content": "To elucidate the role of the beta-sympathetic system in thyrotoxicosis (THY), we examined cardiac sensitivity to infused beta-agonist and compared the effect of beta-blockade with that of resolution of the hyperthyroid state. Beta-sympathetic (beta-SYM) sensitivity was measured as the heart rate response to isoproterenol in THY patients and in normal subjects. The patients with THY showed both lower threshold (P less than 0.05) and increased slope (P less than 0.05) of the heart rate-isoproterenol response, suggesting beta-SYM hypersensitivity. The beta-SYM like features of THY were measured in 7 patients before and 7 days after beta-SYM blockade with propranolol (mean dose 411 +/- 32 mg/day [SEM]) which was shown to block the heart rate response to isoproterenol. These results were compared with those in a similar group of thyrotoxic patients rendered euthyroid with 131I. During beta-SYM blockade, heart rate decreased from 101 +/- 6.3 to 78 +/- 4.6 (P less than 0.01), but the elevated metabolic rate (V02), resting ventilation (VE), and increased hypoxic and hypercapnic ventilatory responses were not significantly affected. In the group rendered euthyroid with 131I, heart rate decreased from 110 +/- 3.5 to 76 +/- 7.8 (P less than 0.02), but in contrast to the result of beta-SYM blockade, a 28% decrease in VO2 (P less than 0.01), 41% decrease in VE (P less than 0.05), a 38% decrease in hypercapnic ventilatory response (P less than 0.05), and a 66% decrease in hypoxic response (P less than 0.03) occurred. During THY, beta-SYM mechanisms are responsible for part of the tachycardia, but the metabolic and ventilatory abnormalities are not beta-SYM mediated.", "contents": "Thyrotoxicosis: comparison of effects of thyroid ablation and beta-adrenergic blockade on metabolic rate and ventilatory control. To elucidate the role of the beta-sympathetic system in thyrotoxicosis (THY), we examined cardiac sensitivity to infused beta-agonist and compared the effect of beta-blockade with that of resolution of the hyperthyroid state. Beta-sympathetic (beta-SYM) sensitivity was measured as the heart rate response to isoproterenol in THY patients and in normal subjects. The patients with THY showed both lower threshold (P less than 0.05) and increased slope (P less than 0.05) of the heart rate-isoproterenol response, suggesting beta-SYM hypersensitivity. The beta-SYM like features of THY were measured in 7 patients before and 7 days after beta-SYM blockade with propranolol (mean dose 411 +/- 32 mg/day [SEM]) which was shown to block the heart rate response to isoproterenol. These results were compared with those in a similar group of thyrotoxic patients rendered euthyroid with 131I. During beta-SYM blockade, heart rate decreased from 101 +/- 6.3 to 78 +/- 4.6 (P less than 0.01), but the elevated metabolic rate (V02), resting ventilation (VE), and increased hypoxic and hypercapnic ventilatory responses were not significantly affected. In the group rendered euthyroid with 131I, heart rate decreased from 110 +/- 3.5 to 76 +/- 7.8 (P less than 0.02), but in contrast to the result of beta-SYM blockade, a 28% decrease in VO2 (P less than 0.01), 41% decrease in VE (P less than 0.05), a 38% decrease in hypercapnic ventilatory response (P less than 0.05), and a 66% decrease in hypoxic response (P less than 0.03) occurred. During THY, beta-SYM mechanisms are responsible for part of the tachycardia, but the metabolic and ventilatory abnormalities are not beta-SYM mediated."}
{"id": "PMID:221523", "title": "An infant with Cushing's disease due to an adrenocorticotropin-producing pituitary adenoma.", "content": "An 8-month old male with Cushing's disease is presented; his clinical presentation and appearance were typical of infants with glucocorticoid excess. Concentrations of cortisol, 17-hydroxyprogesterone, and adrenal androgens were strikingly elevated. High doses of dexamethasone did not suppress the excretion of urinary free cortisol or 17-hydroxycorticoids, and administration of ACTH elicited no further rise in plasma cortisol. Responses of LH, FSH, and PRL to iv LRF and TRF were appropriate for age, but neither TSH nor ACTH rose significantly. Plasma ACTH values were elevated to 700 pg/ml. An intracranial mass lesion superior and anterior to the sella turcica was demonstrated by computerized axial tomography and angiography. An inoperable pituitary adenoma was a massive surrounding fibroblastic reaction was found at craniotomy. The pathological diagnosis of an ACTH-producing pituitary adenoma was confirmed by immunohistochemistry and by the in vitro secretion of ACTH by cells cultured from the tumor.", "contents": "An infant with Cushing's disease due to an adrenocorticotropin-producing pituitary adenoma. An 8-month old male with Cushing's disease is presented; his clinical presentation and appearance were typical of infants with glucocorticoid excess. Concentrations of cortisol, 17-hydroxyprogesterone, and adrenal androgens were strikingly elevated. High doses of dexamethasone did not suppress the excretion of urinary free cortisol or 17-hydroxycorticoids, and administration of ACTH elicited no further rise in plasma cortisol. Responses of LH, FSH, and PRL to iv LRF and TRF were appropriate for age, but neither TSH nor ACTH rose significantly. Plasma ACTH values were elevated to 700 pg/ml. An intracranial mass lesion superior and anterior to the sella turcica was demonstrated by computerized axial tomography and angiography. An inoperable pituitary adenoma was a massive surrounding fibroblastic reaction was found at craniotomy. The pathological diagnosis of an ACTH-producing pituitary adenoma was confirmed by immunohistochemistry and by the in vitro secretion of ACTH by cells cultured from the tumor."}
{"id": "PMID:221525", "title": "Localizaiton of insulinomas by radioimmunoassay of blood obtained by the transport route.", "content": "Transhepatic catheterization of the portal system was performed to obtain blood for RIA of insulin. This technique localized insulinomas in two patients after negative celiac, superior mesenteric, and subselective gastroduodenal arteriograms. The tumors were found in the predicted locations at surgery.", "contents": "Localizaiton of insulinomas by radioimmunoassay of blood obtained by the transport route. Transhepatic catheterization of the portal system was performed to obtain blood for RIA of insulin. This technique localized insulinomas in two patients after negative celiac, superior mesenteric, and subselective gastroduodenal arteriograms. The tumors were found in the predicted locations at surgery."}
{"id": "PMID:221526", "title": "Thyroid-stimulating hormone (TSH) binding to extrathyroidal human tissues: TSH binding to extrathyroidal human tissues: TSH and thyroid-stimulating immunoglobulin effects on adenosine 3',5'-monophosphate in testicular and adrenal tissues.", "content": "Binding of [125I]bovine TSH to human thyroid, testicular, fat, adrenal, liver, kidney, pancreas, and lung cell membranes has been studied. The first four tissues were found to have comparable high affinity constant values; the rest of the tissues lacked high affinity sites. With the exception of fat tissue, the capacities of the high affinity sites of the first four tissues were similar. Bovine TSH concentrations of 100-20,000 microIU/ml stimulated increased cAMP production in human cryopreserved testicular slices. Forty percent of the specimens of thyroid-stimulating immunoglobulin (TSI) from Graves' disease sera also increased human testicular cAMP production. In addition, bovine TSH caused a significant rise in cAMP in the whole decapsulated rat testis. Twenty-five percent of the TSI specimens tested also induced such responses. The rat adrenal gland responded with increased cAMP production to concentrations of 1,000 microU/ml bovine TSH. The physiological significance of high affinity bovine TSH and TSI binding and subsequent cAMP production in nonthyroidal tissues in not known. However, since these stimulators are present in hypothyroidism and hyperthyroidism, respectively, it is possible that the pathophysiological effects of this binding could be of some importance.", "contents": "Thyroid-stimulating hormone (TSH) binding to extrathyroidal human tissues: TSH binding to extrathyroidal human tissues: TSH and thyroid-stimulating immunoglobulin effects on adenosine 3',5'-monophosphate in testicular and adrenal tissues. Binding of [125I]bovine TSH to human thyroid, testicular, fat, adrenal, liver, kidney, pancreas, and lung cell membranes has been studied. The first four tissues were found to have comparable high affinity constant values; the rest of the tissues lacked high affinity sites. With the exception of fat tissue, the capacities of the high affinity sites of the first four tissues were similar. Bovine TSH concentrations of 100-20,000 microIU/ml stimulated increased cAMP production in human cryopreserved testicular slices. Forty percent of the specimens of thyroid-stimulating immunoglobulin (TSI) from Graves' disease sera also increased human testicular cAMP production. In addition, bovine TSH caused a significant rise in cAMP in the whole decapsulated rat testis. Twenty-five percent of the TSI specimens tested also induced such responses. The rat adrenal gland responded with increased cAMP production to concentrations of 1,000 microU/ml bovine TSH. The physiological significance of high affinity bovine TSH and TSI binding and subsequent cAMP production in nonthyroidal tissues in not known. However, since these stimulators are present in hypothyroidism and hyperthyroidism, respectively, it is possible that the pathophysiological effects of this binding could be of some importance."}
{"id": "PMID:221527", "title": "The role of serum lipoproteins in steroidogenesis by the human fetal adrenal cortex.", "content": "In the present investigation it was found that human fetal adrenal tissue maintained in organ culture secreted appreciable quantities of dehydroisoandrosterone sulfate (DS) and cortisol. Pregnenolone was also secreted in significant amounts, principally as the sulfate ester. The highest rate of secretion of these steroids by fetal adrenal tissue occurred when both ACTH and whole human serum were present in the culture medium. In the absence of ACTH, steroid secretion was low. When whole serum was replaced by lipoprotein-poor serum, the steroidogenic response to ACTH was markedly attenuated but not abolished. On the basis of these findings, it is concluded (1) that the human fetal adrenal can synthesize steroid hormones de novo from cholesterol, (2) that ACTH is an important stimulant of steroidogenesis by the human fetal adrenal, and (3) that plasma lipoproteins are a major source of the cholesterol utilized by the human fetal adrenal for steroidogenesis. Hence, it is likely that factors which regulate the production of fetal plasma lipoproteins are important determinants of fetal adrenal steroidogenic activity.", "contents": "The role of serum lipoproteins in steroidogenesis by the human fetal adrenal cortex. In the present investigation it was found that human fetal adrenal tissue maintained in organ culture secreted appreciable quantities of dehydroisoandrosterone sulfate (DS) and cortisol. Pregnenolone was also secreted in significant amounts, principally as the sulfate ester. The highest rate of secretion of these steroids by fetal adrenal tissue occurred when both ACTH and whole human serum were present in the culture medium. In the absence of ACTH, steroid secretion was low. When whole serum was replaced by lipoprotein-poor serum, the steroidogenic response to ACTH was markedly attenuated but not abolished. On the basis of these findings, it is concluded (1) that the human fetal adrenal can synthesize steroid hormones de novo from cholesterol, (2) that ACTH is an important stimulant of steroidogenesis by the human fetal adrenal, and (3) that plasma lipoproteins are a major source of the cholesterol utilized by the human fetal adrenal for steroidogenesis. Hence, it is likely that factors which regulate the production of fetal plasma lipoproteins are important determinants of fetal adrenal steroidogenic activity."}
{"id": "PMID:221530", "title": "Adrenocortical function, electrolyte metabolism, and blood pressure during prolonged adrenocorticotropin infusion in juvenile hypertension.", "content": "The effect of a continuous 5-day ACTH infusion (40 U/24 h) on adrenocorticoid function, electrolyte metabolism, and blood pressure was investigated in eight normotensive children and eight patients with hypertension of unknown origin. There was a continuous rise of plasma cortisol and deoxycorticosterone in all patients. Plasma aldosterone rose transiently in the normotensive and the hypertensive group. A transient kaliuresis and a continuous fall in serum K+ were observed in all patients. ACTH induced sodium retention and weight gain. The observed increase in systolic blood pressure correlated significantly with the cumulative sodium retention in the normotensive and the hypertensive groups. No correlation between sodium retention and diastolic pressure was found. ACTH on a low salt diet (10 meq/24 h) produced a blood pressure rise which was smaller than that on regular salt. The blood pressure rise did not correlate with any of the hormones measured. This study provides evidence for an unidentified ACTH-stimulable adrenal factor capable of raising blood pressure in normotensive children and patients with juvenile hypertension. The ACTH-induced blood pressure rise is only partly salt dependent and the mechanism of the rise remains unclear.", "contents": "Adrenocortical function, electrolyte metabolism, and blood pressure during prolonged adrenocorticotropin infusion in juvenile hypertension. The effect of a continuous 5-day ACTH infusion (40 U/24 h) on adrenocorticoid function, electrolyte metabolism, and blood pressure was investigated in eight normotensive children and eight patients with hypertension of unknown origin. There was a continuous rise of plasma cortisol and deoxycorticosterone in all patients. Plasma aldosterone rose transiently in the normotensive and the hypertensive group. A transient kaliuresis and a continuous fall in serum K+ were observed in all patients. ACTH induced sodium retention and weight gain. The observed increase in systolic blood pressure correlated significantly with the cumulative sodium retention in the normotensive and the hypertensive groups. No correlation between sodium retention and diastolic pressure was found. ACTH on a low salt diet (10 meq/24 h) produced a blood pressure rise which was smaller than that on regular salt. The blood pressure rise did not correlate with any of the hormones measured. This study provides evidence for an unidentified ACTH-stimulable adrenal factor capable of raising blood pressure in normotensive children and patients with juvenile hypertension. The ACTH-induced blood pressure rise is only partly salt dependent and the mechanism of the rise remains unclear."}
{"id": "PMID:221531", "title": "Effects of nicotinic acid therapy on plasma high density lipoprotein subfraction distribution and composition and on apolipoprotein A metabolism.", "content": "This report describes the effects of pharmacologic doses (3 g/d) of nicotinic acid on the plasma distribution and chemical composition of the high density lipoprotein (HDL) subfractions HDL(2) and HDL(3) and examines the influence of the drug on the metabolism of the major HDL apoproteins, apolipoproteins A-I (ApoA-I) and A-II (Apo-II). The drug lowered plasma cholesterol (15%, P < 0.05) and triglyceride (27%, P < 0.01); the former effect a result of a fall in the amount of cholesterol associated with very low density lipoproteins (31%, P < 0.02) and low density lipoproteins (36%, P < 0.02). Conversely, it raised plasma HDL cholesterol (23%, P < 0.05) and increased (by 345%) the plasma HDL(2):HDL(3) ratio. The latter derived from an absolute increment (646%) in circulating HDL(2), coupled with a fall (47%) in HDL(3). This change was not associated with major alterations in the overall cholesterol (free and esterified), triglyceride, phospholipid, or protein content of the subfractions; however, it was accompanied by substantial changes in their protein composition. In particular, the molar ratio of ApoA-I:ApoA-II in HDL(3) declined from 2.7:1 to 2.1:1 during nicotinic acid treatment.Significant perturbations of ApoA-I and ApoA-II metabolism accompanied the drug-induced HDL subfraction redistribution. Specifically, the plasma concentration of ApoA-I rose by 7% (P < 0.05) because of a decrease in its fractional catabolic rate. Moreover, whereas before treatment 6 and 94% of the plasma ApoA-I circulated with HDL(2) and HDL(3), after commencement of nicotinic acid therapy this distribution became 49 and 51% in HDL(2) and HDL(3), respectively. ApoA-II was found mainly in HDL(3), both before and during nicotinic acid treatment. Administration of the drug caused a 14% reduction in its plasma concentration (P < 0.05), which derived principally from a fall (22%, P < 0.01) in its synthetic rate. These data suggest that the effects of nicotinic acid on the HDL subfraction distribution may be mediated via (a) net transfer of ApoA-I from HDL(3) to HDL(2) and (b) a reduction in ApoA-II synthesis. Our present understanding of the association between HDL and atherosclerosis indicates that such changes may have prophylactic value in the prevention of coronary artery disease.", "contents": "Effects of nicotinic acid therapy on plasma high density lipoprotein subfraction distribution and composition and on apolipoprotein A metabolism. This report describes the effects of pharmacologic doses (3 g/d) of nicotinic acid on the plasma distribution and chemical composition of the high density lipoprotein (HDL) subfractions HDL(2) and HDL(3) and examines the influence of the drug on the metabolism of the major HDL apoproteins, apolipoproteins A-I (ApoA-I) and A-II (Apo-II). The drug lowered plasma cholesterol (15%, P < 0.05) and triglyceride (27%, P < 0.01); the former effect a result of a fall in the amount of cholesterol associated with very low density lipoproteins (31%, P < 0.02) and low density lipoproteins (36%, P < 0.02). Conversely, it raised plasma HDL cholesterol (23%, P < 0.05) and increased (by 345%) the plasma HDL(2):HDL(3) ratio. The latter derived from an absolute increment (646%) in circulating HDL(2), coupled with a fall (47%) in HDL(3). This change was not associated with major alterations in the overall cholesterol (free and esterified), triglyceride, phospholipid, or protein content of the subfractions; however, it was accompanied by substantial changes in their protein composition. In particular, the molar ratio of ApoA-I:ApoA-II in HDL(3) declined from 2.7:1 to 2.1:1 during nicotinic acid treatment.Significant perturbations of ApoA-I and ApoA-II metabolism accompanied the drug-induced HDL subfraction redistribution. Specifically, the plasma concentration of ApoA-I rose by 7% (P < 0.05) because of a decrease in its fractional catabolic rate. Moreover, whereas before treatment 6 and 94% of the plasma ApoA-I circulated with HDL(2) and HDL(3), after commencement of nicotinic acid therapy this distribution became 49 and 51% in HDL(2) and HDL(3), respectively. ApoA-II was found mainly in HDL(3), both before and during nicotinic acid treatment. Administration of the drug caused a 14% reduction in its plasma concentration (P < 0.05), which derived principally from a fall (22%, P < 0.01) in its synthetic rate. These data suggest that the effects of nicotinic acid on the HDL subfraction distribution may be mediated via (a) net transfer of ApoA-I from HDL(3) to HDL(2) and (b) a reduction in ApoA-II synthesis. Our present understanding of the association between HDL and atherosclerosis indicates that such changes may have prophylactic value in the prevention of coronary artery disease."}
{"id": "PMID:221532", "title": "Inhibition of angiotensin converting enzyme activity in cultured endothelial cells by hypoxia.", "content": "Endothelial cells in tissue culture degrade bradykinin and convert angiotensin I to angiotensin II. These are both functions of a single dipeptidyl hydrolase, angiotensin converting enzyme. Monolayer cultures were prepared from human, rabbit, pig, and calf vessels. Angiotensin converting enzyme activity was assessed by adding either bradykinin or angiotensin I to the cells in culture flasks, and measuring residual peptide over time by radioimmunoassay. Peptide degradation was inhibited by the specific converting enzyme inhibitor, SQ 20881. The flasks were equilibrated with varying hypoxic gas mixtures: hypoxia rapidly (less than 2 min) decreased enzyme activity and room air restored it as rapidly. The extent to which activity was reduced was a direct function of PO2 (r = 0.93, P less than 0.001), and there was no enzyme activity below a PO2 of 30 mm Hg. Four preparations were studied with respect to decrease in enzyme activity by hypoxia: (a) intact cells in monolayer, (b) sonicated cells, (c) sonicated cells from which converting enzyme was partially dissolved by a detergent, and (d) purified converting enzyme. Hypoxia had progressively less of an inhibiting effect on the enzyme activity of the preparations as the degree of cell integrity decreased. Hypoxia inhibits angiotensin converting enzyme activity in cultured endothelial cells, but the effect of hypoxia is not on the enzyme per se, but appears to be a unique characteristic of the endothelial cell.", "contents": "Inhibition of angiotensin converting enzyme activity in cultured endothelial cells by hypoxia. Endothelial cells in tissue culture degrade bradykinin and convert angiotensin I to angiotensin II. These are both functions of a single dipeptidyl hydrolase, angiotensin converting enzyme. Monolayer cultures were prepared from human, rabbit, pig, and calf vessels. Angiotensin converting enzyme activity was assessed by adding either bradykinin or angiotensin I to the cells in culture flasks, and measuring residual peptide over time by radioimmunoassay. Peptide degradation was inhibited by the specific converting enzyme inhibitor, SQ 20881. The flasks were equilibrated with varying hypoxic gas mixtures: hypoxia rapidly (less than 2 min) decreased enzyme activity and room air restored it as rapidly. The extent to which activity was reduced was a direct function of PO2 (r = 0.93, P less than 0.001), and there was no enzyme activity below a PO2 of 30 mm Hg. Four preparations were studied with respect to decrease in enzyme activity by hypoxia: (a) intact cells in monolayer, (b) sonicated cells, (c) sonicated cells from which converting enzyme was partially dissolved by a detergent, and (d) purified converting enzyme. Hypoxia had progressively less of an inhibiting effect on the enzyme activity of the preparations as the degree of cell integrity decreased. Hypoxia inhibits angiotensin converting enzyme activity in cultured endothelial cells, but the effect of hypoxia is not on the enzyme per se, but appears to be a unique characteristic of the endothelial cell."}
{"id": "PMID:221533", "title": "Effects of glucose and parathyroid hormone on the renal handling of myoinositol by isolated perfused dog kidneys.", "content": "The effects of glucose and parathyroid hormone (PTH) on the transport and metabolism of myoinositol (MI) and [2-(3)H]MI were studied in isolated perfused dog kidneys. Studies during perfusion of kidneys with normal and elevated glucose concentrations demonstrated that under normal conditions the isolated kidney reabsorbed 94.7+/-0.2% of the filtered MI, and the renal production of (3)H-metabolities of MI was 117.9+/-6% of the filtered MI load. This indicated that entry of MI into tubular cells by reabsorption was not the sole pathway for entry into the pool of MI within the kidney undergoing catabolism. High glucose perfusate decreased MI reabsorption to 68.6+/-4.7% and thus decreased delivery of [2-(3)H]MI into the catabolic pool from the reabsorptive pathway. In the high glucose experiments, the rate of [2-(3)H]MI catabolism exceeded [2-(3)H]MI reabsorption by the same fraction as in normal glucose experiments, which indicates that high glucose did not affect nonreabsorptive access of MI to the catabolic site. In contrast to the effects of glucose, PTH administration resulted in an increase in perfusate MI concentration and a decrease in the perfusate [2-(3)H]MI specific activity. Concomitantly, urinary MI and [2-(3)H]MI concentrations were increased, again with a decrease in [2-(3)H]MI specific activity. These results indicate that PTH caused a release of MI into the urine (not the same as decreased MI reabsorption, which would not affect urinary [(3)H]MI specific activity) and into the perfusate of the isolated kidneys. These effects on MI release were about coincidental with the increase in urinary cyclic 3',5'-AMP after PTH and preceded the peak phosphaturic effect of PTH. There was no detectable effect of PTH on MI synthesis from glucose as a source of the MI released into the urine and perfusate. However, PTH temporarily halted accumulation of tritiated MI catabolites. There was no effect of inactivated PTH on urinary cyclic 3',5'-AMP or on MI transport, which indicates that the PTH effect on MI handling was a specific hormonal effect. These studies clarify the renal metabolism of MI, and they demonstrate heretofore unknown effects of PTH on the renal handling and metabolism of MI. The effects of PTH on renal MI metabolism have important implications in renal carbohydrate metabolism and phospholipid turnover.", "contents": "Effects of glucose and parathyroid hormone on the renal handling of myoinositol by isolated perfused dog kidneys. The effects of glucose and parathyroid hormone (PTH) on the transport and metabolism of myoinositol (MI) and [2-(3)H]MI were studied in isolated perfused dog kidneys. Studies during perfusion of kidneys with normal and elevated glucose concentrations demonstrated that under normal conditions the isolated kidney reabsorbed 94.7+/-0.2% of the filtered MI, and the renal production of (3)H-metabolities of MI was 117.9+/-6% of the filtered MI load. This indicated that entry of MI into tubular cells by reabsorption was not the sole pathway for entry into the pool of MI within the kidney undergoing catabolism. High glucose perfusate decreased MI reabsorption to 68.6+/-4.7% and thus decreased delivery of [2-(3)H]MI into the catabolic pool from the reabsorptive pathway. In the high glucose experiments, the rate of [2-(3)H]MI catabolism exceeded [2-(3)H]MI reabsorption by the same fraction as in normal glucose experiments, which indicates that high glucose did not affect nonreabsorptive access of MI to the catabolic site. In contrast to the effects of glucose, PTH administration resulted in an increase in perfusate MI concentration and a decrease in the perfusate [2-(3)H]MI specific activity. Concomitantly, urinary MI and [2-(3)H]MI concentrations were increased, again with a decrease in [2-(3)H]MI specific activity. These results indicate that PTH caused a release of MI into the urine (not the same as decreased MI reabsorption, which would not affect urinary [(3)H]MI specific activity) and into the perfusate of the isolated kidneys. These effects on MI release were about coincidental with the increase in urinary cyclic 3',5'-AMP after PTH and preceded the peak phosphaturic effect of PTH. There was no detectable effect of PTH on MI synthesis from glucose as a source of the MI released into the urine and perfusate. However, PTH temporarily halted accumulation of tritiated MI catabolites. There was no effect of inactivated PTH on urinary cyclic 3',5'-AMP or on MI transport, which indicates that the PTH effect on MI handling was a specific hormonal effect. These studies clarify the renal metabolism of MI, and they demonstrate heretofore unknown effects of PTH on the renal handling and metabolism of MI. The effects of PTH on renal MI metabolism have important implications in renal carbohydrate metabolism and phospholipid turnover."}
{"id": "PMID:221534", "title": "Adenylate cyclase in thymus-derived and bone marrow-derived lymphocytes from normal donors and patients with chronic lymphocytic leukemia.", "content": "Lymphocytes were purified from peripheral blood of normal donors and patients with chronic lymphocytic leukemia (CLL) by Ficoll-Hypaque centrifugation. Adenylate cyclase activity, expressed as picomoles [(32)P]cyclic AMP generated per milligram protein per minute, was 57+/-4 in normals and 26+/-4 in CLL patients. Enzyme activity, expressed as picomoles [(32)P]cyclic AMP generated per 10(6) lymphocytes per minute, was 2.09+/-0.19 for normal lymphocytes and 1.10+/-0.16 for CLL lymphocytes. The differences between normal and CLL peripheral lymphocytes are highly significant (P < 0.001) with either method of calculating activity. Cyclic AMP levels (picomoles per 10(6) lymphocytes) also differed significantly: 1.38+/-0.29 for normals and 0.45+/-0.08 for CLL lymphocytes. Adenylate cyclase was assayed in lymphocytes enriched for bone marrow-derived (B) cells by removing E-rosetted thymus-derived (T) cells, and enriched for T cells by harvesting E-rosetted lymphocytes or by removing B cells with nylon wool absorption. Solutions to simultaneous equations gave the following calculated enzyme activities for pure B- and T-cell subpopulations (in picomoles [(32)P]cyclic AMP generated per milligram mg protein per minute): normal B, 196+/-22; normal T, 30+/-10; CLL B, 34+/-6; CLL T, 19+/-4. Thus. normal B-lymphocyte adenylate cyclase exceeds normal T-lymphocyte activity by more than sixfold, whereas in the case of CLL the enzyme activity in B lymphocytes is markedly reduced to levels comparable to T lymphocytes. The responses of lymphocytes to stimulation with the hormones prostaglandin E(1) and isoproterenol, and with NaF, were assessed. Compared with normal lymphocytes, enzyme activities were reduced in CLL lymphocytes incubated with these agents, but to a degree paralleling the reduced basal activities. Thus, the ratios between stimulated and basal adenylate cyclase levels in Ficoll-Hypaque-purified, normal lymphocytes were 2.3+/-0.1 after incubation with 10 muM isoproterenol, and 3.9+/-0.2 with 10 mM NaF, values which did not differ significantly from those obtained with CLL lymphocytes. When the enzyme activities calculated for purified T- and B-lymphocyte subpopulations were used to derive the stimulation ratios, the responses of normal and CLL T and B cells to these agents were also indistinguishable. The simplest explanation for these findings is a reduced number of normally responsive enzyme sites on the surface membranes of CLL lymphocytes, although alternative explanations are possible.", "contents": "Adenylate cyclase in thymus-derived and bone marrow-derived lymphocytes from normal donors and patients with chronic lymphocytic leukemia. Lymphocytes were purified from peripheral blood of normal donors and patients with chronic lymphocytic leukemia (CLL) by Ficoll-Hypaque centrifugation. Adenylate cyclase activity, expressed as picomoles [(32)P]cyclic AMP generated per milligram protein per minute, was 57+/-4 in normals and 26+/-4 in CLL patients. Enzyme activity, expressed as picomoles [(32)P]cyclic AMP generated per 10(6) lymphocytes per minute, was 2.09+/-0.19 for normal lymphocytes and 1.10+/-0.16 for CLL lymphocytes. The differences between normal and CLL peripheral lymphocytes are highly significant (P < 0.001) with either method of calculating activity. Cyclic AMP levels (picomoles per 10(6) lymphocytes) also differed significantly: 1.38+/-0.29 for normals and 0.45+/-0.08 for CLL lymphocytes. Adenylate cyclase was assayed in lymphocytes enriched for bone marrow-derived (B) cells by removing E-rosetted thymus-derived (T) cells, and enriched for T cells by harvesting E-rosetted lymphocytes or by removing B cells with nylon wool absorption. Solutions to simultaneous equations gave the following calculated enzyme activities for pure B- and T-cell subpopulations (in picomoles [(32)P]cyclic AMP generated per milligram mg protein per minute): normal B, 196+/-22; normal T, 30+/-10; CLL B, 34+/-6; CLL T, 19+/-4. Thus. normal B-lymphocyte adenylate cyclase exceeds normal T-lymphocyte activity by more than sixfold, whereas in the case of CLL the enzyme activity in B lymphocytes is markedly reduced to levels comparable to T lymphocytes. The responses of lymphocytes to stimulation with the hormones prostaglandin E(1) and isoproterenol, and with NaF, were assessed. Compared with normal lymphocytes, enzyme activities were reduced in CLL lymphocytes incubated with these agents, but to a degree paralleling the reduced basal activities. Thus, the ratios between stimulated and basal adenylate cyclase levels in Ficoll-Hypaque-purified, normal lymphocytes were 2.3+/-0.1 after incubation with 10 muM isoproterenol, and 3.9+/-0.2 with 10 mM NaF, values which did not differ significantly from those obtained with CLL lymphocytes. When the enzyme activities calculated for purified T- and B-lymphocyte subpopulations were used to derive the stimulation ratios, the responses of normal and CLL T and B cells to these agents were also indistinguishable. The simplest explanation for these findings is a reduced number of normally responsive enzyme sites on the surface membranes of CLL lymphocytes, although alternative explanations are possible."}
{"id": "PMID:221535", "title": "Evidence for an intrinsic renal tubular defect in mice with genetic hypophosphatemic rickets.", "content": "To investigate the role of parathyroid hormone (PTH) and(or) an intrinsic renal tubular reabsorptive defect for phosphate in mice with hereditary hypophosphatemic rickets, we performed clearance and micropuncture studies in hypophosphatemic mutants and nonaffected littermate controls. Increased fractional excretion of phosphate in mutants (47.2+/-4 vs. 30.8+/-2% in controls) was associated with reduced fractional and absolute reabsorption in the proximal convoluted tubule and more distal sites. Acute thyropara-thyroidectomy (TPTX) increased phosphate reabsorption in both mutants and controls with a fall in fractional phosphate excretion to congruent with7.5% in both groups indicating that PTH modified the degree of phosphaturia in the intact mutants. Absolute reabsorption in the proximal tubule and beyond remained reduced in the mutants, however, possibly because of the reduced filtered load. Serum PTH levels were the same in intact mutants and normals as was renal cortical adenylate cyclase activity both before and after PTH stimulation. To evaluate the possibility that the phosphate wasting was caused by an intrinsic tubular defect that was masked by TPTX, glomerular fluid phosphate concentration was raised by phosphate infusion in TPTX mutants to levels approaching those of control mice. Phosphate excretion rose markedly and fractional reabsorption fell, but there was no change in absolute phosphate reabsorption in either the proximal tubule or beyond, indicating a persistent reabsorptive defect in the absence of PTH. We conclude that hereditary hypophosphatemia in the mouse is associated with a renal tubular defect in phosphate reabsorption, which is independent of PTH and therefore represents a specific intrinsic abnormality of phosphate transport.", "contents": "Evidence for an intrinsic renal tubular defect in mice with genetic hypophosphatemic rickets. To investigate the role of parathyroid hormone (PTH) and(or) an intrinsic renal tubular reabsorptive defect for phosphate in mice with hereditary hypophosphatemic rickets, we performed clearance and micropuncture studies in hypophosphatemic mutants and nonaffected littermate controls. Increased fractional excretion of phosphate in mutants (47.2+/-4 vs. 30.8+/-2% in controls) was associated with reduced fractional and absolute reabsorption in the proximal convoluted tubule and more distal sites. Acute thyropara-thyroidectomy (TPTX) increased phosphate reabsorption in both mutants and controls with a fall in fractional phosphate excretion to congruent with7.5% in both groups indicating that PTH modified the degree of phosphaturia in the intact mutants. Absolute reabsorption in the proximal tubule and beyond remained reduced in the mutants, however, possibly because of the reduced filtered load. Serum PTH levels were the same in intact mutants and normals as was renal cortical adenylate cyclase activity both before and after PTH stimulation. To evaluate the possibility that the phosphate wasting was caused by an intrinsic tubular defect that was masked by TPTX, glomerular fluid phosphate concentration was raised by phosphate infusion in TPTX mutants to levels approaching those of control mice. Phosphate excretion rose markedly and fractional reabsorption fell, but there was no change in absolute phosphate reabsorption in either the proximal tubule or beyond, indicating a persistent reabsorptive defect in the absence of PTH. We conclude that hereditary hypophosphatemia in the mouse is associated with a renal tubular defect in phosphate reabsorption, which is independent of PTH and therefore represents a specific intrinsic abnormality of phosphate transport."}
{"id": "PMID:221536", "title": "Relationship of receptor affinity to the modulation of thyroid hormone nuclear receptor levels and growth hormone synthesis by L-triiodothyronine and iodothyronine analogues in cultured GH1 cells.", "content": "We have previously demonstrated that L-triiodothyronine (L-T3) induces an increase in growth hormone synthesis and messenger RNA in cultured GH1 cells, a rat pituitary cell line. In addition to regulating the growth hormone response, L-T3 elicits a time- and dose-dependent reduction in the level of its nuclear receptor, which is a direct function of the occupancy of the receptor binding site. In this study we have compared the relative affinity of L-T3, triiodothyroacetic acid, D-triiodothyronine (D-T3), and L-thyroxine (L-T4) for the receptor with the induction of the growth hormone synthesis and the ability of these compounds to elicit a reduction in thyroid hormone nuclear receptor levels. Triiodothyroacetic acid and D-T3 were specifically examined because the biologic effect of these compounds in the intact rat is significantly lower than predicted by their affinity for the receptor using isolated rat liver nuclei in vitro. In intact cells each compound demonstrated an excellent relationship between the relative receptor affinity, the induction of growth hormone production, and the concentration-dependent reduction in nuclear receptor levels. With the exception of D-T3, the relative affinity of iodothyronine was identical for the receptor using intact cells in serum-free media, or isolated GH1 cell nuclei in vitro. The apparent receptor affinity of D-T3 with intact cells was 5.5-fold lower than with isolated nuclei, which suggests a decrease in cell entry of D-T3 relative to the other iodothyronines. Quantitation of the [125I]iodothyronine associated with the receptor in GH1 cells after a 36-h incubation with L-125I-T4 was 90% L-T4 and 10% L-T3, which indicates that the major effect of L-T4 in GH1 cells is a result of intrinsic L-T4 activity. Studies with dispersed rat anterior pituitary cells demonstrated that L-T3 induces growth hormone synthesis and elicits a reduction in nuclear receptor levels in the same fashion as GH1 cells. The observation that thyroid hormone influences dispersed rat pituitary cells in a fashion qualitatively similar to GH1 cells may have implications for the growth hormone response of the somatotroph cell in vivo to different thyroidal states.", "contents": "Relationship of receptor affinity to the modulation of thyroid hormone nuclear receptor levels and growth hormone synthesis by L-triiodothyronine and iodothyronine analogues in cultured GH1 cells. We have previously demonstrated that L-triiodothyronine (L-T3) induces an increase in growth hormone synthesis and messenger RNA in cultured GH1 cells, a rat pituitary cell line. In addition to regulating the growth hormone response, L-T3 elicits a time- and dose-dependent reduction in the level of its nuclear receptor, which is a direct function of the occupancy of the receptor binding site. In this study we have compared the relative affinity of L-T3, triiodothyroacetic acid, D-triiodothyronine (D-T3), and L-thyroxine (L-T4) for the receptor with the induction of the growth hormone synthesis and the ability of these compounds to elicit a reduction in thyroid hormone nuclear receptor levels. Triiodothyroacetic acid and D-T3 were specifically examined because the biologic effect of these compounds in the intact rat is significantly lower than predicted by their affinity for the receptor using isolated rat liver nuclei in vitro. In intact cells each compound demonstrated an excellent relationship between the relative receptor affinity, the induction of growth hormone production, and the concentration-dependent reduction in nuclear receptor levels. With the exception of D-T3, the relative affinity of iodothyronine was identical for the receptor using intact cells in serum-free media, or isolated GH1 cell nuclei in vitro. The apparent receptor affinity of D-T3 with intact cells was 5.5-fold lower than with isolated nuclei, which suggests a decrease in cell entry of D-T3 relative to the other iodothyronines. Quantitation of the [125I]iodothyronine associated with the receptor in GH1 cells after a 36-h incubation with L-125I-T4 was 90% L-T4 and 10% L-T3, which indicates that the major effect of L-T4 in GH1 cells is a result of intrinsic L-T4 activity. Studies with dispersed rat anterior pituitary cells demonstrated that L-T3 induces growth hormone synthesis and elicits a reduction in nuclear receptor levels in the same fashion as GH1 cells. The observation that thyroid hormone influences dispersed rat pituitary cells in a fashion qualitatively similar to GH1 cells may have implications for the growth hormone response of the somatotroph cell in vivo to different thyroidal states."}
{"id": "PMID:221537", "title": "Kinetic model for production and metabolism of very low density lipoprotein triglycerides. Evidence for a slow production pathway and results for normolipidemic subjects.", "content": "A model for the synthesis and degradation of very low density lipoprotein triglyceride (VLDL-TG) in man is proposed to explain plasma VLDL-TG radioactivity data from studies conducted over a 48-h interval after injection of glycerol labeled with 14C, 3H, or both. The curve describing the radioactivity of plasma VLDL triglycerides reaches a maximum at about 2 h, after which the decay is biphasic in all cases; the late curvature becoming evident only after 8--12 h. To fit the complex curve, it was necessary to postulate two pathways for the incorporation of plasma glycerol into VLDL-TG, one much slower than the other. A process of stepwise delipidation of VLDL in the plasma compartment, previously proposed for VLDL apoprotein models, was also necessary. Predicted VLDL-TG synthesis rates calculated with this model can differ significantly from those based on experiments of shorter duration in which the slow VLDL-TG component is not apparent. The results of these studies strongly support the interpretation that the late, slow component of the VLDL-TG activity curve is predominantly due to the slowly turning-over precursor compartment in the conversion pathway and is not due either to a slow compartment in the labeled precursor, plasma free glycerol, or to an exchange of plasma VLDL-TG with an extravascular compartment. It also cannot, in these studies, be attributed to a slowly turning-over VLDL-TG moiety in the plasma. The model was tested with data from 59 studies including normal subjects and patients with obesity and(or) various forms of hyperlipoproteinemia. Good fits were obtained in all cases, and the estimated parameter values and their uncertainties for 13 normolipemic nonobese subjects are presented. Sensitivty testing was carried out to determine how critical various parameter estimations are to the assumptions introduced in the modeling.", "contents": "Kinetic model for production and metabolism of very low density lipoprotein triglycerides. Evidence for a slow production pathway and results for normolipidemic subjects. A model for the synthesis and degradation of very low density lipoprotein triglyceride (VLDL-TG) in man is proposed to explain plasma VLDL-TG radioactivity data from studies conducted over a 48-h interval after injection of glycerol labeled with 14C, 3H, or both. The curve describing the radioactivity of plasma VLDL triglycerides reaches a maximum at about 2 h, after which the decay is biphasic in all cases; the late curvature becoming evident only after 8--12 h. To fit the complex curve, it was necessary to postulate two pathways for the incorporation of plasma glycerol into VLDL-TG, one much slower than the other. A process of stepwise delipidation of VLDL in the plasma compartment, previously proposed for VLDL apoprotein models, was also necessary. Predicted VLDL-TG synthesis rates calculated with this model can differ significantly from those based on experiments of shorter duration in which the slow VLDL-TG component is not apparent. The results of these studies strongly support the interpretation that the late, slow component of the VLDL-TG activity curve is predominantly due to the slowly turning-over precursor compartment in the conversion pathway and is not due either to a slow compartment in the labeled precursor, plasma free glycerol, or to an exchange of plasma VLDL-TG with an extravascular compartment. It also cannot, in these studies, be attributed to a slowly turning-over VLDL-TG moiety in the plasma. The model was tested with data from 59 studies including normal subjects and patients with obesity and(or) various forms of hyperlipoproteinemia. Good fits were obtained in all cases, and the estimated parameter values and their uncertainties for 13 normolipemic nonobese subjects are presented. Sensitivty testing was carried out to determine how critical various parameter estimations are to the assumptions introduced in the modeling."}
{"id": "PMID:221538", "title": "Transport of very low density lipoprotein triglycerides in varying degrees of obesity and hypertriglyceridemia.", "content": "Measurements of transport of triglycerides (TG) in very low density lipoproteins (VLDL) were carried out in 59 patients by injection of radioactive glycerol, determinations of specific activities of VLDL-TG for 48 h thereafter, and treatment of the data by multicompartmental analysis. The patients were divided into three groups: normal weight (89-120% ideal weight), mildly obese (120-135% ideal weight), and markedly obese (135% ideal weight). They had varying levels of VLDL-TG ranging from normal to markedly elevated. In many subjects, there was a positive correlation between concentrations and transport of VLDL indicating that overproduction of VLDL-TG contributed to hypertriglyceridemia. In others, and particularly in several markedly obese subjects, transport rates were greatly increased without significant hypertriglyceridemia, suggesting that they had enhanced capacity to clear TG. In all groups, however, there were patients whose degree of hypertriglyceridemia seemed out of proportion to their transport rates. This finding and the fact that many patients have increased secretion of VLDL-TG without elevated plasma TG suggests that both overproduction of VLDL-TG and insufficient enhancement of clearance contributed to the development of hypertriglyceridemia.The data showed a poor correlation between transport rates determined by our multicompartment analysis and single-exponential analysis used previously by other investigators (r = 0.46); this comparison was not improved by segregating patients according to their degree of obesity. Although two conversion pathways (fast and slow synthetic paths) were required to fit the data, there was no correlation between transport rates and the ratio of the two pathways. Also, despite the known pathway of conversion of VLDL to low density lipoprotein, no correlation was found between VLDL-TG transport rates and estimated low density lipoprotein-cholesterol concentrations.", "contents": "Transport of very low density lipoprotein triglycerides in varying degrees of obesity and hypertriglyceridemia. Measurements of transport of triglycerides (TG) in very low density lipoproteins (VLDL) were carried out in 59 patients by injection of radioactive glycerol, determinations of specific activities of VLDL-TG for 48 h thereafter, and treatment of the data by multicompartmental analysis. The patients were divided into three groups: normal weight (89-120% ideal weight), mildly obese (120-135% ideal weight), and markedly obese (135% ideal weight). They had varying levels of VLDL-TG ranging from normal to markedly elevated. In many subjects, there was a positive correlation between concentrations and transport of VLDL indicating that overproduction of VLDL-TG contributed to hypertriglyceridemia. In others, and particularly in several markedly obese subjects, transport rates were greatly increased without significant hypertriglyceridemia, suggesting that they had enhanced capacity to clear TG. In all groups, however, there were patients whose degree of hypertriglyceridemia seemed out of proportion to their transport rates. This finding and the fact that many patients have increased secretion of VLDL-TG without elevated plasma TG suggests that both overproduction of VLDL-TG and insufficient enhancement of clearance contributed to the development of hypertriglyceridemia.The data showed a poor correlation between transport rates determined by our multicompartment analysis and single-exponential analysis used previously by other investigators (r = 0.46); this comparison was not improved by segregating patients according to their degree of obesity. Although two conversion pathways (fast and slow synthetic paths) were required to fit the data, there was no correlation between transport rates and the ratio of the two pathways. Also, despite the known pathway of conversion of VLDL to low density lipoprotein, no correlation was found between VLDL-TG transport rates and estimated low density lipoprotein-cholesterol concentrations."}
{"id": "PMID:221539", "title": "Distribution of beta-endorphin immunoreactivity in normal human pituitary.", "content": "Recent immunohistochemical demonstration of calcitonin in rat pituitary has suggested that calcitonin, in addition to ACTH, endorphins, lipotropins, and melanocyte-stimulating hormones might be derived from a 31,000-dalton glycoprotein percursor molecule. This immunoperoxidase study demonstrates a similar distribution for beta-endorphin and ACTH immunoreactivity in human pituitary; however, the two peptides are not necessarily present in the same cells at all times. Calcitonin could not be demonstrated in human pituitary under conditions suitable for demonstration of the peptide in thyroid C cells. Weakly positive immunostaining could be obtained only with much increase in antiserum concentration and length of incubation, and higher concentrations of calcitonin were needed to abolish staining in preabsorption studies. It thus appears that the immunoreactive calcitonin in human pituitary differs from that in thyroid C cells. Likewise, we could not demonstrate immunoreactive endorphin in any developmental stage of medullary thyroid carcinoma. Our study suggests that caution should be applied in considering a physiologic role for calcitonin in the pituitary and in postulating a common peptide origin for endorphin and calcitonin in humans.", "contents": "Distribution of beta-endorphin immunoreactivity in normal human pituitary. Recent immunohistochemical demonstration of calcitonin in rat pituitary has suggested that calcitonin, in addition to ACTH, endorphins, lipotropins, and melanocyte-stimulating hormones might be derived from a 31,000-dalton glycoprotein percursor molecule. This immunoperoxidase study demonstrates a similar distribution for beta-endorphin and ACTH immunoreactivity in human pituitary; however, the two peptides are not necessarily present in the same cells at all times. Calcitonin could not be demonstrated in human pituitary under conditions suitable for demonstration of the peptide in thyroid C cells. Weakly positive immunostaining could be obtained only with much increase in antiserum concentration and length of incubation, and higher concentrations of calcitonin were needed to abolish staining in preabsorption studies. It thus appears that the immunoreactive calcitonin in human pituitary differs from that in thyroid C cells. Likewise, we could not demonstrate immunoreactive endorphin in any developmental stage of medullary thyroid carcinoma. Our study suggests that caution should be applied in considering a physiologic role for calcitonin in the pituitary and in postulating a common peptide origin for endorphin and calcitonin in humans."}
{"id": "PMID:221540", "title": "Positive rate-sensitive corticosteroid feedback mechanism of ACTH secretion in Cushing's disease.", "content": "To define the nature of the disturbance of the corticosteroid feedback mechanism in Cushing's disease, the dynamic aspects of the ACTH response to corticosteroid administration have been studied in patients with Cushing's disease after total adrenalectomy (C.d. post adx.). The results were compared with those obtained in patients with Addison's disease (control group). Different experimental designs for administration of cortisol were chosen to provide extreme variations in the input signal. The response of the system was evaluated by measuring plasma ACTH concentrations (radioimmunoassay) at short time intervals. Infusion of cortisol at constant rate (50 mg/h for 2 h) resulted in a transient, paradoxical rise in ACTH levels with a maximum at 15 min. (315+/-65%, mean+/-SEM). In contrast, in the control group there was an immediate and rapid decrease in ACTH levels with a significant inhibition after 15 min (80+/-6%, mean+/-SEM). Infusion of 50 mg cortisol for 5 and 15 min, respectively, produced an increase in ACTH levels, which was confined to the time when cortisol levels were rising (maximum: 137+/-30% and 139+/-10% at 5 and 15 min, respectively, mean+/-SEM). This increase corresponded in time to the first decrease in ACTH levels in the Addisonian patients. With bolus injections of 25 mg cortisol, ACTH levels remained unchanged during the first 15 min. The time-course in the patients with C.d. post adx. was essentially the same as in the Addisonian patients. From these results it is concluded that in the patients with C.d. post adx. the rapid, rate-sensitive feedback mechanism was converted into a positive one, whereas the delayed, dose-sensitive mechanism was completely undisturbed. The capacity of dexamethasone to activate rate-sensitive feedback elements was markedly diminished. Accordingly, there were only minor positive feedback effects upon ACTH secretion in the patients with C.d. post adx.", "contents": "Positive rate-sensitive corticosteroid feedback mechanism of ACTH secretion in Cushing's disease. To define the nature of the disturbance of the corticosteroid feedback mechanism in Cushing's disease, the dynamic aspects of the ACTH response to corticosteroid administration have been studied in patients with Cushing's disease after total adrenalectomy (C.d. post adx.). The results were compared with those obtained in patients with Addison's disease (control group). Different experimental designs for administration of cortisol were chosen to provide extreme variations in the input signal. The response of the system was evaluated by measuring plasma ACTH concentrations (radioimmunoassay) at short time intervals. Infusion of cortisol at constant rate (50 mg/h for 2 h) resulted in a transient, paradoxical rise in ACTH levels with a maximum at 15 min. (315+/-65%, mean+/-SEM). In contrast, in the control group there was an immediate and rapid decrease in ACTH levels with a significant inhibition after 15 min (80+/-6%, mean+/-SEM). Infusion of 50 mg cortisol for 5 and 15 min, respectively, produced an increase in ACTH levels, which was confined to the time when cortisol levels were rising (maximum: 137+/-30% and 139+/-10% at 5 and 15 min, respectively, mean+/-SEM). This increase corresponded in time to the first decrease in ACTH levels in the Addisonian patients. With bolus injections of 25 mg cortisol, ACTH levels remained unchanged during the first 15 min. The time-course in the patients with C.d. post adx. was essentially the same as in the Addisonian patients. From these results it is concluded that in the patients with C.d. post adx. the rapid, rate-sensitive feedback mechanism was converted into a positive one, whereas the delayed, dose-sensitive mechanism was completely undisturbed. The capacity of dexamethasone to activate rate-sensitive feedback elements was markedly diminished. Accordingly, there were only minor positive feedback effects upon ACTH secretion in the patients with C.d. post adx."}
{"id": "PMID:221541", "title": "Membrane fluidity in human and mouse Chediak-Higashi leukocytes.", "content": "Polymorphonuclear leukocytes from humans and mice with the Chediak-Higashi syndrome were characterized by spin label electron spin resonance spectrometry. Our results suggest that cells from afflicted mice and humans have membranes more fluid than controls. Order parameters for a spin label that probes near the membrane surface were 0.652 for normals and 0.645 for two Chediak-Higashi patients. Cells from Chediak-Higashi mice showed similar differences, as did isolated plasma membrane fractions. An increased membrane fluidity was also detected with a spin label that probes deeper in the bilayer. In vitro treatment of Chediak-Higashi mouse cells with 0.01 M ascorbate increased the order parameter to normal levels. In vitro incubation of mouse Chediak-Higashi cells with glucose oxidase increased the order parameter, similar to the effect of ascorbate. This increase was abolished when catalase was added to the incubation medium. In vitro incubation with dibutyryl cyclic guanosine monophosphate (1 muM to 0.1 mM) did not normalize order parameters. These results indicate that fluidity of Chediak-Higashi cell membranes was affected by treatments expected to alter the oxidation: reduction potential of the environment but was not affected by treatments expected to alter the ratio of intracellular cyclic nucleotides. The latter treatment would affect microtubule assembly. Therefore, it appears that the membrane fluidity abnormalities as demonstrated by electron spin resonance and the earlier demonstrated microtubule dysfunctions characteristic of Chediak-Higashi cells are coexisting defects and are probably not directly related.", "contents": "Membrane fluidity in human and mouse Chediak-Higashi leukocytes. Polymorphonuclear leukocytes from humans and mice with the Chediak-Higashi syndrome were characterized by spin label electron spin resonance spectrometry. Our results suggest that cells from afflicted mice and humans have membranes more fluid than controls. Order parameters for a spin label that probes near the membrane surface were 0.652 for normals and 0.645 for two Chediak-Higashi patients. Cells from Chediak-Higashi mice showed similar differences, as did isolated plasma membrane fractions. An increased membrane fluidity was also detected with a spin label that probes deeper in the bilayer. In vitro treatment of Chediak-Higashi mouse cells with 0.01 M ascorbate increased the order parameter to normal levels. In vitro incubation of mouse Chediak-Higashi cells with glucose oxidase increased the order parameter, similar to the effect of ascorbate. This increase was abolished when catalase was added to the incubation medium. In vitro incubation with dibutyryl cyclic guanosine monophosphate (1 muM to 0.1 mM) did not normalize order parameters. These results indicate that fluidity of Chediak-Higashi cell membranes was affected by treatments expected to alter the oxidation: reduction potential of the environment but was not affected by treatments expected to alter the ratio of intracellular cyclic nucleotides. The latter treatment would affect microtubule assembly. Therefore, it appears that the membrane fluidity abnormalities as demonstrated by electron spin resonance and the earlier demonstrated microtubule dysfunctions characteristic of Chediak-Higashi cells are coexisting defects and are probably not directly related."}
{"id": "PMID:221542", "title": "Quantitation of the transfer of surface phospholipid of chylomicrons to the high density lipoprotein fraction during the catabolism of chylomicrons in the rat.", "content": "Small chylomicrons (CM) labeled with cholesterol, cholesterol ester, phospholipid, and, in some cases, protein, were used to study the fate of these constituents as the CM are catabolized in the circulations of the hepatectomized and intact rat. In the hepatectomized animal after (1/2) h, CM are greatly reduced in volume, surface area, and diameter. During this period, the CM lost >92% of the mass of their triacylglycerol, >77% of the mass of their phospholipid, and >39% of their protein. Compared to the injected CM, the chemically altered particles, called CM \"remnants,\" have a reduction in volume of 96% and in surface area of 88%. The labeled cholesterol esters remain with the CM remnants but, strikingly, a major fraction of the labeled phospholipids and labeled soluble apoproteins leave the CM and are found in the high density lipoprotein (HDL) fraction. The chemical composition of this HDL fraction contains relatively more phospholipid and less cholesterol ester than normal rat HDL. Because of the difference in composition of HDL between normal rats and those given CM, we estimate that the HDL phospholipid pool increased by congruent with25% by the infusion of congruent with 4-5 mg of CM phospholipid. Approximately 5 mg of phospholipid is secreted on CM by a fed rat in 1 h. The findings in hepatectomized rats indicate that a major fraction of the phospholipid and a minor fraction of the protein (soluble non-B apoproteins) of newly secreted CM are transferred from the CM to the HDL fraction during remnant formation. The same process probably occurs in intact rats except that the remnant particles are rapidly removed from the plasma by the liver and a smaller fraction of the surface of the CM enters the HDL fraction.", "contents": "Quantitation of the transfer of surface phospholipid of chylomicrons to the high density lipoprotein fraction during the catabolism of chylomicrons in the rat. Small chylomicrons (CM) labeled with cholesterol, cholesterol ester, phospholipid, and, in some cases, protein, were used to study the fate of these constituents as the CM are catabolized in the circulations of the hepatectomized and intact rat. In the hepatectomized animal after (1/2) h, CM are greatly reduced in volume, surface area, and diameter. During this period, the CM lost >92% of the mass of their triacylglycerol, >77% of the mass of their phospholipid, and >39% of their protein. Compared to the injected CM, the chemically altered particles, called CM \"remnants,\" have a reduction in volume of 96% and in surface area of 88%. The labeled cholesterol esters remain with the CM remnants but, strikingly, a major fraction of the labeled phospholipids and labeled soluble apoproteins leave the CM and are found in the high density lipoprotein (HDL) fraction. The chemical composition of this HDL fraction contains relatively more phospholipid and less cholesterol ester than normal rat HDL. Because of the difference in composition of HDL between normal rats and those given CM, we estimate that the HDL phospholipid pool increased by congruent with25% by the infusion of congruent with 4-5 mg of CM phospholipid. Approximately 5 mg of phospholipid is secreted on CM by a fed rat in 1 h. The findings in hepatectomized rats indicate that a major fraction of the phospholipid and a minor fraction of the protein (soluble non-B apoproteins) of newly secreted CM are transferred from the CM to the HDL fraction during remnant formation. The same process probably occurs in intact rats except that the remnant particles are rapidly removed from the plasma by the liver and a smaller fraction of the surface of the CM enters the HDL fraction."}
{"id": "PMID:221543", "title": "Modulation of neutrophil function by lysozyme. Potential negative feedback system of inflammation.", "content": "Host responses to infectious organisms should be modulated so that tissue-damaging products of inflammatory cells do not produce excessive destruction of normal tissue. Lysozyme, which is continuously secreted by monocytes, which, in turn, migrate relatively late to inflammatory areas, was found to significantly dampen several responses of neutrophils to inflammatory stimulants. Thus, human lysozyme obtained and purified from the urine of patients with monocytic leukemia (but not its structurally similar and comparably cationic analogue, eggwhite lysozyme) depresses chemotaxis of normal neutrophils to activated complement, bacterial supernate, and N-formylmethionyl-phenylalanine. In addition, human (but not eggwhite) lysozyme depresses oxidative metabolism (hexose monophosphate shunt activity) and superoxide generation of neutrophils. The specificity of the suppressive effects was indicated by inhibition studies with rabbit antihuman lysozyme antibody, and with the trisaccharide of N-acetylglucosamine, a specific inhibitor of lysozyme. The results suggest that lysozyme, a product of inflammatory cells themselves, may function in a negative feedback system to modulate the inflammatory response.", "contents": "Modulation of neutrophil function by lysozyme. Potential negative feedback system of inflammation. Host responses to infectious organisms should be modulated so that tissue-damaging products of inflammatory cells do not produce excessive destruction of normal tissue. Lysozyme, which is continuously secreted by monocytes, which, in turn, migrate relatively late to inflammatory areas, was found to significantly dampen several responses of neutrophils to inflammatory stimulants. Thus, human lysozyme obtained and purified from the urine of patients with monocytic leukemia (but not its structurally similar and comparably cationic analogue, eggwhite lysozyme) depresses chemotaxis of normal neutrophils to activated complement, bacterial supernate, and N-formylmethionyl-phenylalanine. In addition, human (but not eggwhite) lysozyme depresses oxidative metabolism (hexose monophosphate shunt activity) and superoxide generation of neutrophils. The specificity of the suppressive effects was indicated by inhibition studies with rabbit antihuman lysozyme antibody, and with the trisaccharide of N-acetylglucosamine, a specific inhibitor of lysozyme. The results suggest that lysozyme, a product of inflammatory cells themselves, may function in a negative feedback system to modulate the inflammatory response."}
{"id": "PMID:221544", "title": "Human intestinal lipoproteins. Studies in chyluric subjects.", "content": "To explore the role of the human intestine as a source of apolipoproteins, we have studied intestinal lipoproteins and apoprotein secretion in two subjects with chyluria (mesenteric lymphatic-urinary fistulae). After oral corn oil, apolipoprotein A-I (apoA-I) and apolipoprotein A-II (apoA-II) output in urine increased in parallel to urinary triglyceride. One subject, on two occasions, after 40 g of corn oil, excreted 8.4 and 8.6 g of triglyceride together with 196 and 199 mg apoA-I and on one occasion, 56 mg apoA-II. The other subject, after 40 g corn oil, excreted 0.3 g triglyceride and 17.5 mg apoA-I, and, after 100 g of corn oil, excreted 44.8 mg apoA-I and 5.8 mg apoA-II. 14.5+/-2.1% of apoA-I and 17.7+/-4.3% of apoA-II in chylous urine was in the d < 1.006 fraction (chylomicrons and very low density lipoprotein). Calculations based on the amount of apoA-I and apoA-II excreted on triglyceride-rich lipoproteins revealed that for these lipid loads, intestinal secretion could account for 50 and 33% of the calculated daily synthetic rate of apoA-I and apoA-II, respectively. Similarly, subject 2 excreted 48-70% and 14% of the calculated daily synthetic rate of apoA-I and apoA-II, respectively. Chylous urine contained chylomicrons, very low density lipoproteins and high density lipoproteins, all of which contained apoA-I. Chylomicrons and very low density lipoproteins contained a previously unreported human apoprotein of 46,000 mol wt. We have called this apoprotein apoA-IV because of the similarity of its molecular weight and amino acid composition to rat apoA-IV. In sodium dodecyl sulfate gels, chylomicron apoproteins consisted of apoB 3.4+/-0.7%, apoA-IV 10.0+/-3.3%, apoE 4.4+/-0.3%, apoA-I 15.0+/-1.8%, and apoC and apoA-II 43.3+/-11.3%. Very low density lipoprotein contained more apoB and apoA-IV and less apoC than chylomicrons. Ouchterlony immunodiffusion of chylomicron apoproteins revealed the presence of apoC-I, apoC-II, and apoC-III. In contrast, plasma chylomicrons isolated during a nonchyluric phase revealed a markedly altered chylomicron apoprotein pattern when compared with urinary chylomicrons. The major apoproteins in plasma chylomicrons were apoB, apoE, and the C peptides: no apoA-I or apoA-IV were present in sodium dodecyl sulfate gels indicating that major changes in chylomicron apoproteins occur during chylomicron metabolism. When incubated in vitro with plasma, urinary chylomicrons lost apoA-I and apoA-IV and gained apoE and apoC. Loss of apoA-I and apoA-IV was dependent upon the concentration of high density lipoproteins in the incubation mixture. These studies demonstrate that the human intestine secretes significant amounts of apoA-I and apoA-II during lipid absorption. Subsequent transfer of apoproteins from triglyceride-rich lipoproteins to other plasma lipoproteins may represent a mechanism whereby the intestine contributes to plasma apoprotein levels.", "contents": "Human intestinal lipoproteins. Studies in chyluric subjects. To explore the role of the human intestine as a source of apolipoproteins, we have studied intestinal lipoproteins and apoprotein secretion in two subjects with chyluria (mesenteric lymphatic-urinary fistulae). After oral corn oil, apolipoprotein A-I (apoA-I) and apolipoprotein A-II (apoA-II) output in urine increased in parallel to urinary triglyceride. One subject, on two occasions, after 40 g of corn oil, excreted 8.4 and 8.6 g of triglyceride together with 196 and 199 mg apoA-I and on one occasion, 56 mg apoA-II. The other subject, after 40 g corn oil, excreted 0.3 g triglyceride and 17.5 mg apoA-I, and, after 100 g of corn oil, excreted 44.8 mg apoA-I and 5.8 mg apoA-II. 14.5+/-2.1% of apoA-I and 17.7+/-4.3% of apoA-II in chylous urine was in the d < 1.006 fraction (chylomicrons and very low density lipoprotein). Calculations based on the amount of apoA-I and apoA-II excreted on triglyceride-rich lipoproteins revealed that for these lipid loads, intestinal secretion could account for 50 and 33% of the calculated daily synthetic rate of apoA-I and apoA-II, respectively. Similarly, subject 2 excreted 48-70% and 14% of the calculated daily synthetic rate of apoA-I and apoA-II, respectively. Chylous urine contained chylomicrons, very low density lipoproteins and high density lipoproteins, all of which contained apoA-I. Chylomicrons and very low density lipoproteins contained a previously unreported human apoprotein of 46,000 mol wt. We have called this apoprotein apoA-IV because of the similarity of its molecular weight and amino acid composition to rat apoA-IV. In sodium dodecyl sulfate gels, chylomicron apoproteins consisted of apoB 3.4+/-0.7%, apoA-IV 10.0+/-3.3%, apoE 4.4+/-0.3%, apoA-I 15.0+/-1.8%, and apoC and apoA-II 43.3+/-11.3%. Very low density lipoprotein contained more apoB and apoA-IV and less apoC than chylomicrons. Ouchterlony immunodiffusion of chylomicron apoproteins revealed the presence of apoC-I, apoC-II, and apoC-III. In contrast, plasma chylomicrons isolated during a nonchyluric phase revealed a markedly altered chylomicron apoprotein pattern when compared with urinary chylomicrons. The major apoproteins in plasma chylomicrons were apoB, apoE, and the C peptides: no apoA-I or apoA-IV were present in sodium dodecyl sulfate gels indicating that major changes in chylomicron apoproteins occur during chylomicron metabolism. When incubated in vitro with plasma, urinary chylomicrons lost apoA-I and apoA-IV and gained apoE and apoC. Loss of apoA-I and apoA-IV was dependent upon the concentration of high density lipoproteins in the incubation mixture. These studies demonstrate that the human intestine secretes significant amounts of apoA-I and apoA-II during lipid absorption. Subsequent transfer of apoproteins from triglyceride-rich lipoproteins to other plasma lipoproteins may represent a mechanism whereby the intestine contributes to plasma apoprotein levels."}
{"id": "PMID:221545", "title": "In vitro and in vivo refractoriness to thyrotropin stimulation of iodine organification and thyroid hormone secretion.", "content": "Earlier studies indicated that initial exposure of thyroid slices to thyrotropin diminished responsiveness of the adenylate cyclase-cyclic AMP system, glucose oxidation, and (32)P(i) incorporation into phospholipids upon readdition of the hormone. The present studies demonstrate that slices from dog, beef, and human thyroid glands initially incubated with thyrotropin (TSH) were less responsive to subsequent addition of the hormone when organification of iodide was examined. Increasing the amount of TSH did not overcome the refractoriness induced by the initial exposure to the hormone. Furthermore, the stimulatory effects of dibutyryl cyclic AMP and prostagladin E(1) were abolished in slices previously incubated with TSH. Development of such refractoriness did not depend upon new protein synthesis and was not abolished by 1 mM prophylthiouracil in the first incubation. Addition of 0.1 muM thyroxine or triiodothyronine or 1.5 muM iodide during all three incubations did not modify the response to TSH, added for the first time in the third incubation. However, 1 mM iodide in the buffer during all three incubations inhibited the response to TSH during the third incubation. During the refractory period, effects of TSH on colloid droplet formation were also diminished. The in vivo effect of TSH on serum l- triiodothyronine in rats was significantly reduced when the rats had been injected with TSH 8 h earlier. These studies demonstrate that TSH-induced refractoriness also includes effects on organification of iodine and secretion of thyroid hormone. The results cannot be adequately explained by unresponsiveness of adenylate cyclase because effects of dibutyryl cyclic AMP and prostagladin E(1) were also inhibited by prior exposure to TSH.", "contents": "In vitro and in vivo refractoriness to thyrotropin stimulation of iodine organification and thyroid hormone secretion. Earlier studies indicated that initial exposure of thyroid slices to thyrotropin diminished responsiveness of the adenylate cyclase-cyclic AMP system, glucose oxidation, and (32)P(i) incorporation into phospholipids upon readdition of the hormone. The present studies demonstrate that slices from dog, beef, and human thyroid glands initially incubated with thyrotropin (TSH) were less responsive to subsequent addition of the hormone when organification of iodide was examined. Increasing the amount of TSH did not overcome the refractoriness induced by the initial exposure to the hormone. Furthermore, the stimulatory effects of dibutyryl cyclic AMP and prostagladin E(1) were abolished in slices previously incubated with TSH. Development of such refractoriness did not depend upon new protein synthesis and was not abolished by 1 mM prophylthiouracil in the first incubation. Addition of 0.1 muM thyroxine or triiodothyronine or 1.5 muM iodide during all three incubations did not modify the response to TSH, added for the first time in the third incubation. However, 1 mM iodide in the buffer during all three incubations inhibited the response to TSH during the third incubation. During the refractory period, effects of TSH on colloid droplet formation were also diminished. The in vivo effect of TSH on serum l- triiodothyronine in rats was significantly reduced when the rats had been injected with TSH 8 h earlier. These studies demonstrate that TSH-induced refractoriness also includes effects on organification of iodine and secretion of thyroid hormone. The results cannot be adequately explained by unresponsiveness of adenylate cyclase because effects of dibutyryl cyclic AMP and prostagladin E(1) were also inhibited by prior exposure to TSH."}
{"id": "PMID:221546", "title": "Metabolic studies in an unusual case of asymptomatic familial hypobetalipoproteinemia with hypolphalipoproteinemia and fasting chylomicronemia.", "content": "A new kindred with asymptomatic hypobetalipoproteinemia is reported. The proband, age 67, differs from previously described cases in several respects: (a) unusually low levels of low density lipoprotein (LDL) cholesterol (4-8 mg/dl); (b) normal triglyceride levels; (c) low levels of high density lipoprotein; (d) mild fat malabsorption; and (e) a defect in chylomicron clearance. On a high-carbohydrate diet his plasma triglyceride levels, instead of rising, actually fell. Turnover of triglycerides in very low density lipoproteins (VLDL) was low (2.8 mg/kg per h). Fractional catabolic rate of LDL protein was just above the normal range (0.655/d) but net turnover was <10% of normal (0.65 mg/kg per d). The half-life of his chylomicrons was 29 min, five times the normal value. Postheparin lipoprotein lipase activity was normal and apolipoprotein C-II, the activator protein for lipoprotein lipase, was present and functional. Apolipoprotein C-III(1), however, was not detected in the VLDL fraction, a finding previously reported in patients with abetalipoproteinemia. Fecal excretion of cholesterol was almost twice normal; total sterol balance was increased by congruent with40%. The unusual features in the proband that distinguish him from previously described cases and from his affected first-degree relatives suggested that, in addition to the basic gene defect affecting LDL metabolism, he might have a second abnormality affecting clearance of chylomicrons and VLDL. The ratio of apolipoprotein E(3) to E(2) in his VLDL fraction was 0.93, just below the lower limit of normal, suggesting heterozygosity for E(3) deficiency. Whether or not this contributes to his hypertriglyceridemia remains to be established.", "contents": "Metabolic studies in an unusual case of asymptomatic familial hypobetalipoproteinemia with hypolphalipoproteinemia and fasting chylomicronemia. A new kindred with asymptomatic hypobetalipoproteinemia is reported. The proband, age 67, differs from previously described cases in several respects: (a) unusually low levels of low density lipoprotein (LDL) cholesterol (4-8 mg/dl); (b) normal triglyceride levels; (c) low levels of high density lipoprotein; (d) mild fat malabsorption; and (e) a defect in chylomicron clearance. On a high-carbohydrate diet his plasma triglyceride levels, instead of rising, actually fell. Turnover of triglycerides in very low density lipoproteins (VLDL) was low (2.8 mg/kg per h). Fractional catabolic rate of LDL protein was just above the normal range (0.655/d) but net turnover was <10% of normal (0.65 mg/kg per d). The half-life of his chylomicrons was 29 min, five times the normal value. Postheparin lipoprotein lipase activity was normal and apolipoprotein C-II, the activator protein for lipoprotein lipase, was present and functional. Apolipoprotein C-III(1), however, was not detected in the VLDL fraction, a finding previously reported in patients with abetalipoproteinemia. Fecal excretion of cholesterol was almost twice normal; total sterol balance was increased by congruent with40%. The unusual features in the proband that distinguish him from previously described cases and from his affected first-degree relatives suggested that, in addition to the basic gene defect affecting LDL metabolism, he might have a second abnormality affecting clearance of chylomicrons and VLDL. The ratio of apolipoprotein E(3) to E(2) in his VLDL fraction was 0.93, just below the lower limit of normal, suggesting heterozygosity for E(3) deficiency. Whether or not this contributes to his hypertriglyceridemia remains to be established."}
{"id": "PMID:221547", "title": "Production of hybridomas secreting monoclonal antibodies against the lympholine osteoclast activating factor.", "content": "The human lympholine osteoclast activating factor (OAF) is thought to be involved in several bone-destroying diseases. The current studies were designed to produce monoclonal antibodies against OAF for use in the subsequent design of immunoassays for OAF in clinical samples. Spleen cells from mice immunized with purified human OAF were hybridized with mouse plasmacytoma cells in vitro to yield hybridomas. Several clones of these hybridomas secreted into the culture medium antibodies, which neutralized the biological activity of OAF at dilutions as high as 1:100,000 relative to the initial culture medium. These antibodies did not interfere with the activities of parathyroid hormone in the same systems. These results represent the first report of monoclonal antibodies against a human lympholine, and validate the concept that hybridoma production is a useful technique for developing antibodies against weak or scarce antigens.", "contents": "Production of hybridomas secreting monoclonal antibodies against the lympholine osteoclast activating factor. The human lympholine osteoclast activating factor (OAF) is thought to be involved in several bone-destroying diseases. The current studies were designed to produce monoclonal antibodies against OAF for use in the subsequent design of immunoassays for OAF in clinical samples. Spleen cells from mice immunized with purified human OAF were hybridized with mouse plasmacytoma cells in vitro to yield hybridomas. Several clones of these hybridomas secreted into the culture medium antibodies, which neutralized the biological activity of OAF at dilutions as high as 1:100,000 relative to the initial culture medium. These antibodies did not interfere with the activities of parathyroid hormone in the same systems. These results represent the first report of monoclonal antibodies against a human lympholine, and validate the concept that hybridoma production is a useful technique for developing antibodies against weak or scarce antigens."}
{"id": "PMID:221548", "title": "Modulation of in vitro erythropoiesis. Studies with euthyroid and hypothyroid dogs.", "content": "The interactions of  adrenergic agonists and thyroid hormones on the growth of erythroid colony-forming units were studied in cultures of dog marrow before and after the establishment of hypothyroidism. Erythroid colony growth in cultures form euthyroid dogs was enhanced by isoproterenol and other adrenergic agonists having beta 2-receptor specificity. With hypothyroidism, however, this responsiveness was lost, and sensitivity to alpha-agonists, such as phenylephrine and norepinephrine, was acquired. This alteration in receptor specificity appeared to be dependent upon thyroid hormone and was rapidly reversible. Preincubation of marrow cells from hypothyroid animals with thyroid hormone resulted in the reappearance of responsiveness to beta-adrenergic agonists and the loss of sensitivity to alpha-agonists. These findings are in agreement with previous suggestions that beta-adrenergic receptor activity is modulated by thyroid hormone levels and demonstrate that the specificity of adrenergic modulations of erythropoiesis in culture may accurately reflect the thyroid status of the intact animal.", "contents": "Modulation of in vitro erythropoiesis. Studies with euthyroid and hypothyroid dogs. The interactions of  adrenergic agonists and thyroid hormones on the growth of erythroid colony-forming units were studied in cultures of dog marrow before and after the establishment of hypothyroidism. Erythroid colony growth in cultures form euthyroid dogs was enhanced by isoproterenol and other adrenergic agonists having beta 2-receptor specificity. With hypothyroidism, however, this responsiveness was lost, and sensitivity to alpha-agonists, such as phenylephrine and norepinephrine, was acquired. This alteration in receptor specificity appeared to be dependent upon thyroid hormone and was rapidly reversible. Preincubation of marrow cells from hypothyroid animals with thyroid hormone resulted in the reappearance of responsiveness to beta-adrenergic agonists and the loss of sensitivity to alpha-agonists. These findings are in agreement with previous suggestions that beta-adrenergic receptor activity is modulated by thyroid hormone levels and demonstrate that the specificity of adrenergic modulations of erythropoiesis in culture may accurately reflect the thyroid status of the intact animal."}
{"id": "PMID:221549", "title": "Alpha-1-antitrypsin deficiency and hepatocellular carcinoma.", "content": "Forty-two cases of hepatocellular carcinoma (HCC) were examined for the presence of the inclusions of alpha-1-antitrypsin (AAT), which indicate a carrier state for the Pi Z gene. These were found in the non-neoplastic liver tissue of two cases of HCC and in one of the 98 control livers, a difference that is not statistically significant. Typical globules of AAT deficiency were not found in HCC cells. One-quarter of HCCs, however, contained cells which showed diffuse cytoplasmic staining for AAT, a pattern seen also in the non-neoplastic livers.", "contents": "Alpha-1-antitrypsin deficiency and hepatocellular carcinoma. Forty-two cases of hepatocellular carcinoma (HCC) were examined for the presence of the inclusions of alpha-1-antitrypsin (AAT), which indicate a carrier state for the Pi Z gene. These were found in the non-neoplastic liver tissue of two cases of HCC and in one of the 98 control livers, a difference that is not statistically significant. Typical globules of AAT deficiency were not found in HCC cells. One-quarter of HCCs, however, contained cells which showed diffuse cytoplasmic staining for AAT, a pattern seen also in the non-neoplastic livers."}
{"id": "PMID:221550", "title": "Viral exposure and abnormal liver function in haemophilia.", "content": "Several studies have recently documented the presence of persistently abnormal liver function tests in asymptomatic haemophiliacs. While the aetiology is unknown it is possible that repeated exposure to agents transmitted in blood products may be important. This study has attempted to determine the prevalence of viral exposure and its relationship to liver function in this multitransfused group of individuals. The prevalence of viral antibodies with the exception of antibody to hepatitis B surface antigen (anti-HBs) and cytomegalovirus (CMV) was normal when compared to that in the general population. Hepatitis B surface antigen (HBsAg) was not detected, but anti-HBs was found in 83% of patients; 50% of patients had abnormal liver function. However, liver function tests were normal in all patients with mild haemophilia and were only rarely abnormal in patients who had no detectable antibody to CMV, Epstein-Barr virus (EBV), and HBsAg. This study demonstrates that multiple transfusions of blood products, that is, cryoprecipitate and factor concentrates, do not increase the risk of exposure to the viruses studied with the exception of hepatitis B virus.", "contents": "Viral exposure and abnormal liver function in haemophilia. Several studies have recently documented the presence of persistently abnormal liver function tests in asymptomatic haemophiliacs. While the aetiology is unknown it is possible that repeated exposure to agents transmitted in blood products may be important. This study has attempted to determine the prevalence of viral exposure and its relationship to liver function in this multitransfused group of individuals. The prevalence of viral antibodies with the exception of antibody to hepatitis B surface antigen (anti-HBs) and cytomegalovirus (CMV) was normal when compared to that in the general population. Hepatitis B surface antigen (HBsAg) was not detected, but anti-HBs was found in 83% of patients; 50% of patients had abnormal liver function. However, liver function tests were normal in all patients with mild haemophilia and were only rarely abnormal in patients who had no detectable antibody to CMV, Epstein-Barr virus (EBV), and HBsAg. This study demonstrates that multiple transfusions of blood products, that is, cryoprecipitate and factor concentrates, do not increase the risk of exposure to the viruses studied with the exception of hepatitis B virus."}
{"id": "PMID:221551", "title": "Memory deficits associated with senescence: a neurophysiological and behavioral study in the rat.", "content": "Neurophysiological and behavioral measures were obtained from 32 senescent (28--34 mo) and 32 mature adult (10--16 mo) rats. Extracellularly recorded synaptic responses were obtained from electrodes chronically implanted in the fascia dentata and perforant path. The rats were first tested on a circular platform, which favored the use of spatial cues for its solution, and the senescent rats were shown to exhibit poorer memory for the rewarded place. When granule cell synaptic responses were recorded after a single session of very brief high-frequency stimulation, the amount of elevation and time course of decline were equivalent between age groups. Af ter three repetitions, however, the young rats maintained the increased synaptic strength for at least 14 days, whereas the old rats declined after the first session. The amount of synaptic enhancement was statistically correlated with the ability to perform the circular platform task both within and between groups. Furthermore, the aftereffects of the high-frequency stimulation selectively impaired the old rats' spontaneous alternation behavior on a T-maze. Certain other neurophysiological and electroencephalographic measures did not distinguish between age groups. The results are discussed in terms of the synaptic theory of memory formation and of their relevance to the aging process.", "contents": "Memory deficits associated with senescence: a neurophysiological and behavioral study in the rat. Neurophysiological and behavioral measures were obtained from 32 senescent (28--34 mo) and 32 mature adult (10--16 mo) rats. Extracellularly recorded synaptic responses were obtained from electrodes chronically implanted in the fascia dentata and perforant path. The rats were first tested on a circular platform, which favored the use of spatial cues for its solution, and the senescent rats were shown to exhibit poorer memory for the rewarded place. When granule cell synaptic responses were recorded after a single session of very brief high-frequency stimulation, the amount of elevation and time course of decline were equivalent between age groups. Af ter three repetitions, however, the young rats maintained the increased synaptic strength for at least 14 days, whereas the old rats declined after the first session. The amount of synaptic enhancement was statistically correlated with the ability to perform the circular platform task both within and between groups. Furthermore, the aftereffects of the high-frequency stimulation selectively impaired the old rats' spontaneous alternation behavior on a T-maze. Certain other neurophysiological and electroencephalographic measures did not distinguish between age groups. The results are discussed in terms of the synaptic theory of memory formation and of their relevance to the aging process."}
{"id": "PMID:221552", "title": "Inhibition of adenylate cyclase in human blood platelets by 9-substituted adenine derivatives.", "content": "A series of 9-substituted adenine derivatives inhibited adenylate cyclase activity (ATP pyrophosphate-lyase (cyclizing) EC 4.6.1.1) of a particulate preparation of human blood platelets. A 3--6 fold elevation of adenylate cyclase activity by prostaglandin E1 (PGE1) was inhibited in a concentration-related manner by 9-(tetrahydro-5-methyl-2-furyl) adenine (SQ 22,538), 9-(tetrahydro-2-furyl) adenine (SQ 22,536), 9-cyclopentyladenine (SQ 22,534), 9-furfuryladenine (sQ 4647) and 9-benzyladenine (SQ 218611). The I50 values ranged from 21 microM for SQ 22,538 to 140 microM for SQ 21,611. These same adenine derivatives reversed the inhibition by PGE1 of ADP-induced aggregation and the PGE1-stimulated elevation of adenosine 3':5'-monophosphate (cyclic AMP). The reversal of platelet aggregation inhibition by SQ 22,536 and SQ 4647 was concentration-related with I50 values of 30 microM in each case, whereas SQ 22,534 and SQ 21,611 reversed inhibition by 30% at 100 microM. SQ 22,536, SQ 22,534 and SQ 21,611 also blocked the increase in cyclic AMP levels in a concentration-related manner with I50 values of 1, 4 and 60 microM, respectively. SQ 4647 inhibited the elevation of cyclic AMP by more than 85% at 1000 microM. The adenine derivatives had no effect on platelet aggregation or on cyclic AMP levels in the absence of PGE1. These results provide additional evidence that the inhibition of platelet aggregation by PGE1 is mediated by cyclic AMP.", "contents": "Inhibition of adenylate cyclase in human blood platelets by 9-substituted adenine derivatives. A series of 9-substituted adenine derivatives inhibited adenylate cyclase activity (ATP pyrophosphate-lyase (cyclizing) EC 4.6.1.1) of a particulate preparation of human blood platelets. A 3--6 fold elevation of adenylate cyclase activity by prostaglandin E1 (PGE1) was inhibited in a concentration-related manner by 9-(tetrahydro-5-methyl-2-furyl) adenine (SQ 22,538), 9-(tetrahydro-2-furyl) adenine (SQ 22,536), 9-cyclopentyladenine (SQ 22,534), 9-furfuryladenine (sQ 4647) and 9-benzyladenine (SQ 218611). The I50 values ranged from 21 microM for SQ 22,538 to 140 microM for SQ 21,611. These same adenine derivatives reversed the inhibition by PGE1 of ADP-induced aggregation and the PGE1-stimulated elevation of adenosine 3':5'-monophosphate (cyclic AMP). The reversal of platelet aggregation inhibition by SQ 22,536 and SQ 4647 was concentration-related with I50 values of 30 microM in each case, whereas SQ 22,534 and SQ 21,611 reversed inhibition by 30% at 100 microM. SQ 22,536, SQ 22,534 and SQ 21,611 also blocked the increase in cyclic AMP levels in a concentration-related manner with I50 values of 1, 4 and 60 microM, respectively. SQ 4647 inhibited the elevation of cyclic AMP by more than 85% at 1000 microM. The adenine derivatives had no effect on platelet aggregation or on cyclic AMP levels in the absence of PGE1. These results provide additional evidence that the inhibition of platelet aggregation by PGE1 is mediated by cyclic AMP."}
{"id": "PMID:221553", "title": "The stability constants of some metal ion complexes of 3',5'-cyclic AMP.", "content": "The stability constants of complexes of 3', 5'-cyclic AMP with Mg2+, Ca2+, Mn2+, Ni2+ and Co2+ were estimated at 30 degrees C in solutions of ionic strength about 0.15 containing about 130 mM K+ or tetramethylammonium ions. Values between 13 and 22 M-1 were obtained, indicating that only about 2% of cyclic AMP is present as metal complexes in vivo, but that at commonly used in vitro concentrations of 10 mM bivalent metal ions, 10--20% of cyclic AMP is present as metal complexes. The possible significance of these metal complexes, for example as competitive inhibitors, is discussed.", "contents": "The stability constants of some metal ion complexes of 3',5'-cyclic AMP. The stability constants of complexes of 3', 5'-cyclic AMP with Mg2+, Ca2+, Mn2+, Ni2+ and Co2+ were estimated at 30 degrees C in solutions of ionic strength about 0.15 containing about 130 mM K+ or tetramethylammonium ions. Values between 13 and 22 M-1 were obtained, indicating that only about 2% of cyclic AMP is present as metal complexes in vivo, but that at commonly used in vitro concentrations of 10 mM bivalent metal ions, 10--20% of cyclic AMP is present as metal complexes. The possible significance of these metal complexes, for example as competitive inhibitors, is discussed."}
{"id": "PMID:221554", "title": "1,N6-Etheno-2-aza-adenosine 3', 5'-cyclic phosphate: human erythrocyte membrane binding and activation of membrane protein kinase.", "content": "The relative efficiency of 1,N6-etheno-2aza-adenosine 3', 5'-monophosphate (cyclic 2-aza-epsilon AMP), 1,N6-etenoadenosine 3', 5'-monophosphate (cyclic epsilon AMP) and cyclic AMP in activation of membrane protein kinase and binding to membrane was examined using isolated membranes from human erythrocytes. Cyclic 2-aza-epsilon AMP was 81% as active as cyclic AMP in erythrocyte membrane binding and activation of membrane protein kinase. On the other hand, cyclic epsilon AMP was 37% as active toward membrane protein kinase and 29% toward membrane cyclic AMP binding. Since we have previously shown that the fluorescence of cyclic 2-aza-epsilon AMP is highly sensitive to the polarity of solvents, the high efficiency of cyclic 2-aza-epsilon AMP to substitute for cyclic amp suggests that it may be a suitable microenvironmental fluorescent probe for cyclic AMP binding sites.", "contents": "1,N6-Etheno-2-aza-adenosine 3', 5'-cyclic phosphate: human erythrocyte membrane binding and activation of membrane protein kinase. The relative efficiency of 1,N6-etheno-2aza-adenosine 3', 5'-monophosphate (cyclic 2-aza-epsilon AMP), 1,N6-etenoadenosine 3', 5'-monophosphate (cyclic epsilon AMP) and cyclic AMP in activation of membrane protein kinase and binding to membrane was examined using isolated membranes from human erythrocytes. Cyclic 2-aza-epsilon AMP was 81% as active as cyclic AMP in erythrocyte membrane binding and activation of membrane protein kinase. On the other hand, cyclic epsilon AMP was 37% as active toward membrane protein kinase and 29% toward membrane cyclic AMP binding. Since we have previously shown that the fluorescence of cyclic 2-aza-epsilon AMP is highly sensitive to the polarity of solvents, the high efficiency of cyclic 2-aza-epsilon AMP to substitute for cyclic amp suggests that it may be a suitable microenvironmental fluorescent probe for cyclic AMP binding sites."}
{"id": "PMID:221555", "title": "Catecholamine-induced desensitization involves an uncoupling of beta-adrenergic receptors and adenylate cyclase.", "content": "Incubation of 1321N1 astrocytoma cells for 15 min with 1 microM (-)-isoproterenol resulted in a 50-65% loss of isoproterenol-stimulated adenylate cyclase activity. No decrease occurred in basal adenylate cyclase activity or in the density of beta-adrenergic receptors as assessed by (125I)-hydroxybenzylpindolol binding. Concentration-effect studies indicated that the apparent affinity of isoproterenol for inhibition of (125I)-hydroxbenzylpindolol binding was decreased by approximately 10-fold in membranes prepared from cells that had been exposed to 1 umM isoproterenol for 15 min. In the presence of GTP there was a shift to the right of the concentration-effect curve for isoproterenol in control membranes. GTP had little effect on the apparent affinity of isoproterenol in desensitized membranes. In desensitized cells that were subsequently washed free of catecholamine, the decrement in isoproterenol-stimulated adenylate cyclase activity and the decrease in the capacity of isoproterenol to inhibit 125IHYP binding returned to control levels within 15 min. These data are consistent with the hypothesis that an early event in the process of desensitization in 1321N1 cells involves a reversible uncoupling of beta-adrenergic receptors and adenylate cyclase.", "contents": "Catecholamine-induced desensitization involves an uncoupling of beta-adrenergic receptors and adenylate cyclase. Incubation of 1321N1 astrocytoma cells for 15 min with 1 microM (-)-isoproterenol resulted in a 50-65% loss of isoproterenol-stimulated adenylate cyclase activity. No decrease occurred in basal adenylate cyclase activity or in the density of beta-adrenergic receptors as assessed by (125I)-hydroxybenzylpindolol binding. Concentration-effect studies indicated that the apparent affinity of isoproterenol for inhibition of (125I)-hydroxbenzylpindolol binding was decreased by approximately 10-fold in membranes prepared from cells that had been exposed to 1 umM isoproterenol for 15 min. In the presence of GTP there was a shift to the right of the concentration-effect curve for isoproterenol in control membranes. GTP had little effect on the apparent affinity of isoproterenol in desensitized membranes. In desensitized cells that were subsequently washed free of catecholamine, the decrement in isoproterenol-stimulated adenylate cyclase activity and the decrease in the capacity of isoproterenol to inhibit 125IHYP binding returned to control levels within 15 min. These data are consistent with the hypothesis that an early event in the process of desensitization in 1321N1 cells involves a reversible uncoupling of beta-adrenergic receptors and adenylate cyclase."}
{"id": "PMID:221556", "title": "The nature of covalent complexes of phosphoproteins with collagen in the bovine dentin matrix.", "content": "The bovine dentin matrix still contains some noncollagenous proteins after thorough extraction and decalcification. These have been obtained following digestion of the matrix by cyanogen bromide. Peptides containing non-collagenous portions were isolated by chromatography on diethylaminoethyl cellulose columns and fractionated on hydroxyapatite columns. Several fractions were obtained. The principal component was a complex between a highly-phosphorylated serine-aspartic acid-rich protein and a collagen peptide. These collagenous and non-collagenous moieties could not be separated from each other even under highly dissociative solvent conditions. After digestion with collagenase, the resulting phosphoprotein fraction still contained a few residues of hydroxyproline and hydroxylysine, and an enhanced content of proline, compared to the equivalent directly extractable phosphophoryn of the matrix. These data were interpreted as indicating that the phosphophoryn which is not extractable in 0.5M ethylenediaminetetraacetic acid is in fact covalently bound to some specific section of the matrix collagen. The covalent modification of the collagen matrix with highly acidic phosphoproteins may have an important role in the mineralization process.", "contents": "The nature of covalent complexes of phosphoproteins with collagen in the bovine dentin matrix. The bovine dentin matrix still contains some noncollagenous proteins after thorough extraction and decalcification. These have been obtained following digestion of the matrix by cyanogen bromide. Peptides containing non-collagenous portions were isolated by chromatography on diethylaminoethyl cellulose columns and fractionated on hydroxyapatite columns. Several fractions were obtained. The principal component was a complex between a highly-phosphorylated serine-aspartic acid-rich protein and a collagen peptide. These collagenous and non-collagenous moieties could not be separated from each other even under highly dissociative solvent conditions. After digestion with collagenase, the resulting phosphoprotein fraction still contained a few residues of hydroxyproline and hydroxylysine, and an enhanced content of proline, compared to the equivalent directly extractable phosphophoryn of the matrix. These data were interpreted as indicating that the phosphophoryn which is not extractable in 0.5M ethylenediaminetetraacetic acid is in fact covalently bound to some specific section of the matrix collagen. The covalent modification of the collagen matrix with highly acidic phosphoproteins may have an important role in the mineralization process."}
{"id": "PMID:221563", "title": "Effect of donor age on the binding and degradation of low density lipoproteins by cultured human arterial smooth muscle cells.", "content": "The ability of human arterial smooth muscle cells growing in tissue culture to bind, incorporate and degrade low density lipoproteins (LDL) was studied as a function of cell donor age from 5 to 71 years. LDL binding to cell surface receptors did not change with donor age. However, LDL degradation was significantly decreased in cells from older donors. These results may be relevant to the enhanced accumulation of cellular cholesterol and LDL observed in the aging human artery. Thus, impaired LDL degradation by arterial smooth muscle cells may be one of several factors involved in the accelerated development of atherosclerosis with aging.", "contents": "Effect of donor age on the binding and degradation of low density lipoproteins by cultured human arterial smooth muscle cells. The ability of human arterial smooth muscle cells growing in tissue culture to bind, incorporate and degrade low density lipoproteins (LDL) was studied as a function of cell donor age from 5 to 71 years. LDL binding to cell surface receptors did not change with donor age. However, LDL degradation was significantly decreased in cells from older donors. These results may be relevant to the enhanced accumulation of cellular cholesterol and LDL observed in the aging human artery. Thus, impaired LDL degradation by arterial smooth muscle cells may be one of several factors involved in the accelerated development of atherosclerosis with aging."}
{"id": "PMID:221564", "title": "Effect of experimental prolongation of life span on lipofuscin content and lysosomal enzyme activity in the brain of the housefly, Musca domestica.", "content": "The effect of experimental prolongation of life span on the rate of lipofuscin accumulation in the giant neurons of the brain and lysosomal enzyme activity in the head was studied in the male housefly, Musca domestica. The median and the maximum life span of the flies was extended twofold by varying their flight activity. The rate of lipofuscin accumulation was significantly faster in short-lived, high-activity flies as compared to the long-lived, low-activity flies. The maximal content of lipofuscin in the neurons was similar in both groups but was reached at a much older age in the low-activity flies. Age-associated profiles of the activities of the lysosomal enzymes beta-glycerophosphatase and beta-acetylglucosaminidase did not correspond to the mortality characteristics of the housefly populations. The results support the view that lipofuscin represents an integral aspect of aging and may be used as a cellular marker for physiological age whereas lysosomal enzyme activities do not seem to be directly related to the rate of aging.", "contents": "Effect of experimental prolongation of life span on lipofuscin content and lysosomal enzyme activity in the brain of the housefly, Musca domestica. The effect of experimental prolongation of life span on the rate of lipofuscin accumulation in the giant neurons of the brain and lysosomal enzyme activity in the head was studied in the male housefly, Musca domestica. The median and the maximum life span of the flies was extended twofold by varying their flight activity. The rate of lipofuscin accumulation was significantly faster in short-lived, high-activity flies as compared to the long-lived, low-activity flies. The maximal content of lipofuscin in the neurons was similar in both groups but was reached at a much older age in the low-activity flies. Age-associated profiles of the activities of the lysosomal enzymes beta-glycerophosphatase and beta-acetylglucosaminidase did not correspond to the mortality characteristics of the housefly populations. The results support the view that lipofuscin represents an integral aspect of aging and may be used as a cellular marker for physiological age whereas lysosomal enzyme activities do not seem to be directly related to the rate of aging."}
{"id": "PMID:221565", "title": "Sleep in young and old rats.", "content": "Five young rats, age 152--175 days, and six old rats, age 782--801 days, all of the F-344 strain, were compared by electronic methods for amplitude of slow wave activity during sleep and for other sleep parameters. Unlike humans, who show a pronounced loss of slow wave activity with advanced age, no significant difference in delta activity could be detected between young and old rats. Several hypotheses about the species difference were reviewed. Young and old rats, however, did show several differences in other sleep parameters which parallel those observed in humans. These age-related changes were a moderate decrease in the percent of total sleep time spent in paradoxical sleep, a decrease in the length of sleep bouts, an increase in the number of sleep bouts, and a decrease in the amplitude of the diurnal rhythm of sleep.", "contents": "Sleep in young and old rats. Five young rats, age 152--175 days, and six old rats, age 782--801 days, all of the F-344 strain, were compared by electronic methods for amplitude of slow wave activity during sleep and for other sleep parameters. Unlike humans, who show a pronounced loss of slow wave activity with advanced age, no significant difference in delta activity could be detected between young and old rats. Several hypotheses about the species difference were reviewed. Young and old rats, however, did show several differences in other sleep parameters which parallel those observed in humans. These age-related changes were a moderate decrease in the percent of total sleep time spent in paradoxical sleep, a decrease in the length of sleep bouts, an increase in the number of sleep bouts, and a decrease in the amplitude of the diurnal rhythm of sleep."}
{"id": "PMID:221570", "title": "Influence of different routes of anti-tumor immunization: alternative induction of tumor immunity and tumor enhancement.", "content": "Chickens and quails were immunized in parallel either i.v. or intramuscularly (i.m.) with lectin column-purified antigens from chick embryo cells that were transformed in vitro by avain sarcoma virus (ASV). After five to six injections, immunity of the animals was tested by challenge with ASV into the wing webs. Whereas tumor growth was inhibited after i.v. immunization with respect to incidence rate and time of tumor appearance, tumor growth was enhanced after i.m. injection. Animals that were injected with normal cell antigens served as controls. Spleen cells from only those animals that were immunized i.v. exerted a cytotoxic effect in vitro against ASV-transformed cells, whereas spleen cells from i.m. injected animals, in contrast, suppressed such cytotoxicity. The search for serum blocking or arming factors suggested that sera from i.m. injected animals block cellular cytotoxicity whereas sera from i.v. immunized animals render normal spleen cells cytotoxic (arming effect). The use of viruses from different subgroups and of antigens from gp85-lacking ASV-transformed cells indicates that immune effects were obtained against tumor cell surface antigens that differ from the antigen that is involved in virus neutralization (s-gp85).", "contents": "Influence of different routes of anti-tumor immunization: alternative induction of tumor immunity and tumor enhancement. Chickens and quails were immunized in parallel either i.v. or intramuscularly (i.m.) with lectin column-purified antigens from chick embryo cells that were transformed in vitro by avain sarcoma virus (ASV). After five to six injections, immunity of the animals was tested by challenge with ASV into the wing webs. Whereas tumor growth was inhibited after i.v. immunization with respect to incidence rate and time of tumor appearance, tumor growth was enhanced after i.m. injection. Animals that were injected with normal cell antigens served as controls. Spleen cells from only those animals that were immunized i.v. exerted a cytotoxic effect in vitro against ASV-transformed cells, whereas spleen cells from i.m. injected animals, in contrast, suppressed such cytotoxicity. The search for serum blocking or arming factors suggested that sera from i.m. injected animals block cellular cytotoxicity whereas sera from i.v. immunized animals render normal spleen cells cytotoxic (arming effect). The use of viruses from different subgroups and of antigens from gp85-lacking ASV-transformed cells indicates that immune effects were obtained against tumor cell surface antigens that differ from the antigen that is involved in virus neutralization (s-gp85)."}
{"id": "PMID:221571", "title": "Phenotypic and functional effects of the motheaten gene on murine B and T lymphocytes.", "content": "Lymphoid cells from C57BL/6 mice homozygous for the me gene exhibit multiple phenotypic and functional abnormalities from early as one week of age. In the B cell population these include a reduction in the frequency of detectable surface Ig+ cells, alterations in the level of expression of surface IgM and IgD, an increase in the frequency of large cells, plasma cells and TNP-specific plaque forming cePS. Together these findings provide strong evidence for polyclonal activation of B cells. The high level of expression of xenotropic MuLV gp70 by me/me spleen and lymph node cells provides further evidence for lymphoid cell activation. In preliminary studies, me/me T cells appeared to be phenotypically and functionally less affected by the me gene. The distribution of Thy 1.2 on the surface of spleen and lymph node T cells varied from low to normal and the mitogenic responses to Con A and PHA were depressed. It remains to be determined what the basic deficiency in me/me mice is and whether it affects primarily B cells or all lymphoid cells.", "contents": "Phenotypic and functional effects of the motheaten gene on murine B and T lymphocytes. Lymphoid cells from C57BL/6 mice homozygous for the me gene exhibit multiple phenotypic and functional abnormalities from early as one week of age. In the B cell population these include a reduction in the frequency of detectable surface Ig+ cells, alterations in the level of expression of surface IgM and IgD, an increase in the frequency of large cells, plasma cells and TNP-specific plaque forming cePS. Together these findings provide strong evidence for polyclonal activation of B cells. The high level of expression of xenotropic MuLV gp70 by me/me spleen and lymph node cells provides further evidence for lymphoid cell activation. In preliminary studies, me/me T cells appeared to be phenotypically and functionally less affected by the me gene. The distribution of Thy 1.2 on the surface of spleen and lymph node T cells varied from low to normal and the mitogenic responses to Con A and PHA were depressed. It remains to be determined what the basic deficiency in me/me mice is and whether it affects primarily B cells or all lymphoid cells."}
{"id": "PMID:221574", "title": "Antigenic properties and molecular weights of murine leukemia virus-binding proteins.", "content": "A murine T lymphoma cell line, WEHI-22, has been studied for the presence of murine leukemia virus-binding proteins and for the presence of cell surface molecules that share antigens with mouse immunoglobulins. With surface radioiodination, detergent disruption, and immunoprecipitation, a 60 to 70,000-dalton molecule has been described that is recognized by chicken anti-mouse immunoglobulin serum. In competition experiments this molecule cross-reacts with highly purified mouse IgM myeloma proteins. A cell surface molecule of similar size can be shown to bind to mouse leukemia viruses. Pre-precipitation of the WEHI-22 cell surface material with chicken anti-mouse immunoglobulin removes the material binding to leukemia viruses.", "contents": "Antigenic properties and molecular weights of murine leukemia virus-binding proteins. A murine T lymphoma cell line, WEHI-22, has been studied for the presence of murine leukemia virus-binding proteins and for the presence of cell surface molecules that share antigens with mouse immunoglobulins. With surface radioiodination, detergent disruption, and immunoprecipitation, a 60 to 70,000-dalton molecule has been described that is recognized by chicken anti-mouse immunoglobulin serum. In competition experiments this molecule cross-reacts with highly purified mouse IgM myeloma proteins. A cell surface molecule of similar size can be shown to bind to mouse leukemia viruses. Pre-precipitation of the WEHI-22 cell surface material with chicken anti-mouse immunoglobulin removes the material binding to leukemia viruses."}
{"id": "PMID:221576", "title": "Hybrid resistance to BALB/c plasmacytomas. II. Radiation sensitivity and silica insensitivity of resistance to MPC-11.", "content": "Resistance to the BALB/c plasmacytoma MPC-11 by F1 hybrids between BALB/c and four C57BL/10 congenic resistant strains was abrogated or reduced by 450 rads total body irradiation but was unaffected by intravenous injection of 3 to 4 mg of silica. The results are consistent with the idea that hybrid resistance to MPC-11 depends on an active immune response and is different from Hh-1 controlled hybrid resistance.", "contents": "Hybrid resistance to BALB/c plasmacytomas. II. Radiation sensitivity and silica insensitivity of resistance to MPC-11. Resistance to the BALB/c plasmacytoma MPC-11 by F1 hybrids between BALB/c and four C57BL/10 congenic resistant strains was abrogated or reduced by 450 rads total body irradiation but was unaffected by intravenous injection of 3 to 4 mg of silica. The results are consistent with the idea that hybrid resistance to MPC-11 depends on an active immune response and is different from Hh-1 controlled hybrid resistance."}
{"id": "PMID:221578", "title": "Lymphocyte activation by the tumor-promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA).", "content": "TPA, a highly active tumor-promoting agent, is an effective mitogen for primate peripheral blood lymphocytes. Optimal stimulation of human lymphocytes was obtained 4 days after the addition of TPA at a concentration of 7.5 ng/ml. Lymphocyte fractionation experiments demonstrated that both T and B cells incorporated 3H-thymidine significantly in response to TPA. Lymphocyte blastogenesis was not due to the reactivation of latent herpesviruses by the tumor promoter, since similar responses to TPA were obtained with virus-genome positive or negative cells. Increased levels of DNA synthesis were observed when TPA was added to marmoset, baboon, rhesus monkey, or chimpanzee peripheral blood lymphocytes. Canine peripheral blood lymphocytes and spleen cells from guinea pigs, rats, and mice were not stimulated by TPA. These observations suggest that TPA-induced lymphocyte blastogenesis may be useful for studies of lymphocyte activation and of the molecular mechanisms of action of tumor-promoting phorbol esters.", "contents": "Lymphocyte activation by the tumor-promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA). TPA, a highly active tumor-promoting agent, is an effective mitogen for primate peripheral blood lymphocytes. Optimal stimulation of human lymphocytes was obtained 4 days after the addition of TPA at a concentration of 7.5 ng/ml. Lymphocyte fractionation experiments demonstrated that both T and B cells incorporated 3H-thymidine significantly in response to TPA. Lymphocyte blastogenesis was not due to the reactivation of latent herpesviruses by the tumor promoter, since similar responses to TPA were obtained with virus-genome positive or negative cells. Increased levels of DNA synthesis were observed when TPA was added to marmoset, baboon, rhesus monkey, or chimpanzee peripheral blood lymphocytes. Canine peripheral blood lymphocytes and spleen cells from guinea pigs, rats, and mice were not stimulated by TPA. These observations suggest that TPA-induced lymphocyte blastogenesis may be useful for studies of lymphocyte activation and of the molecular mechanisms of action of tumor-promoting phorbol esters."}
{"id": "PMID:221580", "title": "Mechanisms of leukemogenesis. I. Generation of autoreactive lymphocytes in response to a murine leukemia virus.", "content": "Examined in this paper is the capacity of 334C murine leukemia virus (MuLV) to stimulate the generation of virus-specific cytotoxic effector cells in mice of the C57BL/6 strain that are relatively resistant to Friend, Moloney, and Rauscher (FMR) MuLV-induced leukemia, and in BALB/c mice that are relatively susceptible to leukemia induced by FMR MuLV. Generation of cytotoxicity requires in vivo administration of the virus followed by in vitro culture of lymphoid cells from virus-injected animals. Lymphoid cells from MuLV-resistant C57BL/6 donors develop high levels of specific cytotoxicity after secondary in vitro stimulation with syngeneic MuLV-induced tumor cells. Cells derived from these same donors, cultured in the absence of MuLV-induced tumor cells, fail to exhibit cytotoxicity. Secondary in vitro stimulation of lymphocytes from MuLV-susceptible BALB/c animals results not only in generation of cytotoxic reactivity against syngeneic MuLV-induced tumor cells but also induces apparently autoreactive effector cells capable of lysing other H-2d tumor cells as well as normal peritoneal cells bearing H-2d antigens. Moreover, generation of cytotoxicity by BALB/c lymphocytes occurs whether or not MuLV-induced tumor cells are included in the secondary culture system.", "contents": "Mechanisms of leukemogenesis. I. Generation of autoreactive lymphocytes in response to a murine leukemia virus. Examined in this paper is the capacity of 334C murine leukemia virus (MuLV) to stimulate the generation of virus-specific cytotoxic effector cells in mice of the C57BL/6 strain that are relatively resistant to Friend, Moloney, and Rauscher (FMR) MuLV-induced leukemia, and in BALB/c mice that are relatively susceptible to leukemia induced by FMR MuLV. Generation of cytotoxicity requires in vivo administration of the virus followed by in vitro culture of lymphoid cells from virus-injected animals. Lymphoid cells from MuLV-resistant C57BL/6 donors develop high levels of specific cytotoxicity after secondary in vitro stimulation with syngeneic MuLV-induced tumor cells. Cells derived from these same donors, cultured in the absence of MuLV-induced tumor cells, fail to exhibit cytotoxicity. Secondary in vitro stimulation of lymphocytes from MuLV-susceptible BALB/c animals results not only in generation of cytotoxic reactivity against syngeneic MuLV-induced tumor cells but also induces apparently autoreactive effector cells capable of lysing other H-2d tumor cells as well as normal peritoneal cells bearing H-2d antigens. Moreover, generation of cytotoxicity by BALB/c lymphocytes occurs whether or not MuLV-induced tumor cells are included in the secondary culture system."}
{"id": "PMID:221581", "title": "Hypocomplementemia associated with naturally occurring lymphosarcoma in pet cats.", "content": "Eighty cats were classified by indirect immunofluorescence and histologic diagnosis into four categories: normal, feline leukemia virus (FeLV) infected; normal noninfected; lymphosarcoma-FeLV infected; lymphosarcoma, no FeLV present. All viremic cats with lymphosarcoma were found to be hypocomplementemic and activation of the complement system had occurred via the classical pathway. Sera of cats with lymphosarcoma in the absence of FeLV had varying levels of total hemolytic complement (TCH50) ranging from normal to hypocomplementemic. Approximately 50% of the cats that were viremic but histologically and clinically free of disease had TCH50 levels within normal range, and the remainder exhibited varying degrees of hypocomplementemia.", "contents": "Hypocomplementemia associated with naturally occurring lymphosarcoma in pet cats. Eighty cats were classified by indirect immunofluorescence and histologic diagnosis into four categories: normal, feline leukemia virus (FeLV) infected; normal noninfected; lymphosarcoma-FeLV infected; lymphosarcoma, no FeLV present. All viremic cats with lymphosarcoma were found to be hypocomplementemic and activation of the complement system had occurred via the classical pathway. Sera of cats with lymphosarcoma in the absence of FeLV had varying levels of total hemolytic complement (TCH50) ranging from normal to hypocomplementemic. Approximately 50% of the cats that were viremic but histologically and clinically free of disease had TCH50 levels within normal range, and the remainder exhibited varying degrees of hypocomplementemia."}
{"id": "PMID:221582", "title": "Macrophage activation by mycobacterial water soluble compounds and synthetic muramyl dipeptide.", "content": "The adjuvant effects of mycobacteria can be replaced by more chemically defined isolates of the cell walls including a water soluble fraction (WSA) and by the synthetic analog N-acetyl-muramyl-L-alanyl-D-isoglutamine (MDP), which is the minimal structure required for adjuvanticity. These compounds can directly activate macrophages as determined by an increase in spreading and adherence and by an elevated synthesis of the enzyme collagenase. Moreover, this increase in collagenase production is modulated by enhanced production of prostaglandins that influences intracellular levels of cyclic AMP. In addition, both MDP and WSA induced macrophages to produce a biologically active mediator that triggers quiescent fibroblasts into active proliferation. It thus appears that a mechanism for mycobacterial adjuvant action as determined with MDP and WSA is via activation of macrophages, which may then precipitate a multiplicity of other reactions resulting in enhanced immune phenomena. Furthermore, the granulomatous and fibrotic reactions associated with mycobacterial infection may be a consequence of this direct activation of macrophages.", "contents": "Macrophage activation by mycobacterial water soluble compounds and synthetic muramyl dipeptide. The adjuvant effects of mycobacteria can be replaced by more chemically defined isolates of the cell walls including a water soluble fraction (WSA) and by the synthetic analog N-acetyl-muramyl-L-alanyl-D-isoglutamine (MDP), which is the minimal structure required for adjuvanticity. These compounds can directly activate macrophages as determined by an increase in spreading and adherence and by an elevated synthesis of the enzyme collagenase. Moreover, this increase in collagenase production is modulated by enhanced production of prostaglandins that influences intracellular levels of cyclic AMP. In addition, both MDP and WSA induced macrophages to produce a biologically active mediator that triggers quiescent fibroblasts into active proliferation. It thus appears that a mechanism for mycobacterial adjuvant action as determined with MDP and WSA is via activation of macrophages, which may then precipitate a multiplicity of other reactions resulting in enhanced immune phenomena. Furthermore, the granulomatous and fibrotic reactions associated with mycobacterial infection may be a consequence of this direct activation of macrophages."}
{"id": "PMID:221583", "title": "Antibody blockade of lysis by T lymphocyte effectors generated against syngeneic SV40 transformed cells.", "content": "Antibody blockade of cell-mediated lysis was used to probe the cell surface structures recognized by T lymphocytes generated to syngeneic SV40 virus-transformed mouse cells. Alloantisera to H-2 antigens were highly effective in inhibiting lysis. Anti-H2 antibody blockade of lysis was haplotype specific even on transformed F1 target cells. Inhibition occurred only when antibody was bound to the target cell. Antibody binding to the effector did not inhibit lysis. Inhibition required that antibody be bound to the H-2 molecule itself; antibody to molecules associated with H-2, such as beta2-microglobulin, had no effect. Attempts to block lysis by using antisera to known virus-coded molecules were uniformly unsuccessful. These results are discussed in light of current controversy concerning the nature of the SV40 virus-specific transplantation antigen.", "contents": "Antibody blockade of lysis by T lymphocyte effectors generated against syngeneic SV40 transformed cells. Antibody blockade of cell-mediated lysis was used to probe the cell surface structures recognized by T lymphocytes generated to syngeneic SV40 virus-transformed mouse cells. Alloantisera to H-2 antigens were highly effective in inhibiting lysis. Anti-H2 antibody blockade of lysis was haplotype specific even on transformed F1 target cells. Inhibition occurred only when antibody was bound to the target cell. Antibody binding to the effector did not inhibit lysis. Inhibition required that antibody be bound to the H-2 molecule itself; antibody to molecules associated with H-2, such as beta2-microglobulin, had no effect. Attempts to block lysis by using antisera to known virus-coded molecules were uniformly unsuccessful. These results are discussed in light of current controversy concerning the nature of the SV40 virus-specific transplantation antigen."}
{"id": "PMID:221584", "title": "Variations in expression of xenotropic murine leukemia virus genomes in lymphoid tissues of NZB mice.", "content": "Lymphocytes from Thy, Sp, LN, and BM and NZB mice were tested for expression of X-MuLV genomes as cell surface gp70 (XenCSA) or infectious virus. The results demonstrate major dissociations for these parameters of X-MuLV expression in different lymphoid compartments and suggest that factors involved in T lymphocyte differentiation modify the levels of expression in these two modes.", "contents": "Variations in expression of xenotropic murine leukemia virus genomes in lymphoid tissues of NZB mice. Lymphocytes from Thy, Sp, LN, and BM and NZB mice were tested for expression of X-MuLV genomes as cell surface gp70 (XenCSA) or infectious virus. The results demonstrate major dissociations for these parameters of X-MuLV expression in different lymphoid compartments and suggest that factors involved in T lymphocyte differentiation modify the levels of expression in these two modes."}
{"id": "PMID:221586", "title": "Enhanced immune response late in primary cytomegalovirus infection of mice.", "content": "Murine cytomegalovirus (MCMV) infection has been previously shown to depress humoral and cell-mediated functions to non-MCMV antigens. In this report we show that in C3D2 mice undergoing nonlethal primary infection the depressed anti-sheep RBC plaque-forming cell (PFC) response is followed by an enhanced PFC response. Infected mice often generated twice the number of PFC per spleen than that of control mice. Total numbers of spleen cells as well as the recovery of virus from spleens of infected mice did not distinguish the depressed from the enhanced phase of the response. Investigation of the kinetics of the response revealed a defect in shutdown regulation. This enhanced PFC response during primary MCMV infection was not reflected in measurements of serum hemagglutinin. These findings suggest that MCMV induces an impairment of immunoregulation.", "contents": "Enhanced immune response late in primary cytomegalovirus infection of mice. Murine cytomegalovirus (MCMV) infection has been previously shown to depress humoral and cell-mediated functions to non-MCMV antigens. In this report we show that in C3D2 mice undergoing nonlethal primary infection the depressed anti-sheep RBC plaque-forming cell (PFC) response is followed by an enhanced PFC response. Infected mice often generated twice the number of PFC per spleen than that of control mice. Total numbers of spleen cells as well as the recovery of virus from spleens of infected mice did not distinguish the depressed from the enhanced phase of the response. Investigation of the kinetics of the response revealed a defect in shutdown regulation. This enhanced PFC response during primary MCMV infection was not reflected in measurements of serum hemagglutinin. These findings suggest that MCMV induces an impairment of immunoregulation."}
{"id": "PMID:221587", "title": "Differentiation antigens on normal and Abelson virus transformed lymphocytes.", "content": "Rabbit antisera to Abelson leukemia virus (A-MuLV)-induced murine lymphomas have been analyzed by absorption with a variety of murine lymphoma lines. Antibody binding to a panel of cell lines and normal lymphocytes was visualized by using hapten-sandwich indirect membrane immunofluorescence. Novel membrane antigens thereby detected are shared between lymphosarcomas, B lymphomas, normal B lymphocytes, and normal membrane immunoglobulin negative (sIg-) bone marrow cells, but are not found on T cells, thymic lymphomas, plasmacytoid lymphomas, or myelomas. The existence of such shared differentiation antigens suggests that sIg- A-MuLV-induced lymphosarcomas may be transformed B cell precursors. Since differences in the expression of these antigens on individual plasma-cytoid lymphoma lines were found, this category of lymphomas may include cells at a variety of differentiation states.", "contents": "Differentiation antigens on normal and Abelson virus transformed lymphocytes. Rabbit antisera to Abelson leukemia virus (A-MuLV)-induced murine lymphomas have been analyzed by absorption with a variety of murine lymphoma lines. Antibody binding to a panel of cell lines and normal lymphocytes was visualized by using hapten-sandwich indirect membrane immunofluorescence. Novel membrane antigens thereby detected are shared between lymphosarcomas, B lymphomas, normal B lymphocytes, and normal membrane immunoglobulin negative (sIg-) bone marrow cells, but are not found on T cells, thymic lymphomas, plasmacytoid lymphomas, or myelomas. The existence of such shared differentiation antigens suggests that sIg- A-MuLV-induced lymphosarcomas may be transformed B cell precursors. Since differences in the expression of these antigens on individual plasma-cytoid lymphoma lines were found, this category of lymphomas may include cells at a variety of differentiation states."}
{"id": "PMID:221589", "title": "The effects of mitogens on the expression of Epstein-Barr virus antigens in human lymphoid cell lines.", "content": "Treatment of human lymphoblastoid cells with either phytohemagglutinin (PHA), concanavalin A, Staphylococcus protein A, or polyinosinic acid-polycytidylic acid, in combination with 5-iodo-2' deoxyuridine (IUdR) markedly increased the expression of Epstein-Barr virus (EBV) early antigen (EA) relative to IUdR alone. Such treatment did not, however, modify the production of virus capsid antigen in any of the lymphoid cell lines tested. The effect of PHA on EA induction in Raji cells was not accompanied by changes in the incorporation of labeled precursors into cellular DNA, or in the intracellular concentration of either adenosine 3'5' cyclic monophosphate or guanosine 3'5' cyclic monophosphate. However, those mitogens that stimulated EA expression in Raji cells also increased the fluorescence polarization of 1,6 diphenyl 1,3,5-hexatriene-labeled Raji cells. The possible role of cell surface changes in the mitogen activation of latent EBV in human lymphoblastoid cells is discussed.", "contents": "The effects of mitogens on the expression of Epstein-Barr virus antigens in human lymphoid cell lines. Treatment of human lymphoblastoid cells with either phytohemagglutinin (PHA), concanavalin A, Staphylococcus protein A, or polyinosinic acid-polycytidylic acid, in combination with 5-iodo-2' deoxyuridine (IUdR) markedly increased the expression of Epstein-Barr virus (EBV) early antigen (EA) relative to IUdR alone. Such treatment did not, however, modify the production of virus capsid antigen in any of the lymphoid cell lines tested. The effect of PHA on EA induction in Raji cells was not accompanied by changes in the incorporation of labeled precursors into cellular DNA, or in the intracellular concentration of either adenosine 3'5' cyclic monophosphate or guanosine 3'5' cyclic monophosphate. However, those mitogens that stimulated EA expression in Raji cells also increased the fluorescence polarization of 1,6 diphenyl 1,3,5-hexatriene-labeled Raji cells. The possible role of cell surface changes in the mitogen activation of latent EBV in human lymphoblastoid cells is discussed."}
{"id": "PMID:221592", "title": "Fractionation and immunologic assessment of KCl-extracted cardiac antigens in coxsackievirus B3 virus-induced myocarditis.", "content": "Hypertonic salt extracts prepared from the heart tissues of adolescent CD-1 mice were fractionated on Sephadex G-100 columns. Two separate fractions were obtained. Fraction I, containing the antigenic immunoreactive activity, was able to inhibit the migration of CVB3-PPD immune mouse peritoneal exudate cells (IMPEC) as well as PEC from mice infected with CVB3 virus alone. Fraction II did not have antigenic activity as assessed by the agarose droplet cell migration inhibition assay. As controls, Fraction I prepared from the livers of spleens of CVB3-infected CD-1 mice was unable to inhibit the migration of CVB3 IMPEC. Unimmunized or \"normal\" mouse peritoneal exudate cells (NMPEC) were not inhibited by Fraction I. Antibodies prepared against Fractions I and II were unable to neutralize CVB3m virus in the plaque reduction test, and polyacrylamide gel analysis revealed multiple bands in 10% SDS gels.", "contents": "Fractionation and immunologic assessment of KCl-extracted cardiac antigens in coxsackievirus B3 virus-induced myocarditis. Hypertonic salt extracts prepared from the heart tissues of adolescent CD-1 mice were fractionated on Sephadex G-100 columns. Two separate fractions were obtained. Fraction I, containing the antigenic immunoreactive activity, was able to inhibit the migration of CVB3-PPD immune mouse peritoneal exudate cells (IMPEC) as well as PEC from mice infected with CVB3 virus alone. Fraction II did not have antigenic activity as assessed by the agarose droplet cell migration inhibition assay. As controls, Fraction I prepared from the livers of spleens of CVB3-infected CD-1 mice was unable to inhibit the migration of CVB3 IMPEC. Unimmunized or \"normal\" mouse peritoneal exudate cells (NMPEC) were not inhibited by Fraction I. Antibodies prepared against Fractions I and II were unable to neutralize CVB3m virus in the plaque reduction test, and polyacrylamide gel analysis revealed multiple bands in 10% SDS gels."}
{"id": "PMID:221593", "title": "Enzyme immunoassay for feline oncornavirus-associated cell membrane antigen (FOCMA) and detection of FOCMA in cell extract by enzyme immunoassay inhibition test.", "content": "An enzyme immunoassay (EIA) for FOCMA has been developed. The assay uses alkaline phosphatase-conjugated rabbit anti-cat IgG as the second antibody and p-nitrophenyl phosphate as the substrate for the enzyme to detect cat FOCMA antibody bound to the target cells. In comparison with the indirect immunofluorescence (IIF) test, which was originally used for FOCMA assay, our results showed a good correlation between the two methods. The EIA gives a more objective measure of FOCMA reactivity than does IIF. FOCMA was successfully extracted from FOCMA-positive cell membranes by 0.5% Triton X-100 and further fractionated by ammonium sulfate. The FOCMA activity was assayed by IIF and EIA inhibition test. Most of the FOCMA activity was found in the fractions precipitated by 30% and 50% ammonium sulfate saturation.", "contents": "Enzyme immunoassay for feline oncornavirus-associated cell membrane antigen (FOCMA) and detection of FOCMA in cell extract by enzyme immunoassay inhibition test. An enzyme immunoassay (EIA) for FOCMA has been developed. The assay uses alkaline phosphatase-conjugated rabbit anti-cat IgG as the second antibody and p-nitrophenyl phosphate as the substrate for the enzyme to detect cat FOCMA antibody bound to the target cells. In comparison with the indirect immunofluorescence (IIF) test, which was originally used for FOCMA assay, our results showed a good correlation between the two methods. The EIA gives a more objective measure of FOCMA reactivity than does IIF. FOCMA was successfully extracted from FOCMA-positive cell membranes by 0.5% Triton X-100 and further fractionated by ammonium sulfate. The FOCMA activity was assayed by IIF and EIA inhibition test. Most of the FOCMA activity was found in the fractions precipitated by 30% and 50% ammonium sulfate saturation."}
{"id": "PMID:221594", "title": "Beta adrenergic receptor binding on polymorphonuclear leukocytes in atopic dermatitis.", "content": "It has been postulated that the patient with atopic dermatitis has defective beta adrenergic receptor function. However, a more generalized defect is suggested by the observation that cyclic AMP generation is diminished in these patients following stimulation with both isoproterenol and PGE1. To determine the nature of this abnormality, we measured beta adrenergic receptor binding directly on polymorphonuclear leukocyte membranes using the radiolabeled beta adrenergic antagonist (-) [3H]dihydroalprenolol (DHA). DHA binding was studied in 6 mild and 9 moderate-to-severe atopic dermatitis patients, and 8 normal controls using a subsaturating concentration of DHA (0.5 nM) to estimate receptor affinity and a saturating concentration of DHA (30 mM) to determine the total number of receptors per cell. No significant differences (p greater than .05) were found in the total number of receptors per PMN between the control population (805 +/- 95) and the mild atopic dermatitis patients (745 +/- 91) or the moderate to severe group (621 +/- 79). In addition, no significant differences in receptor affinity were found among any of the 3 study groups. These findings suggest that beta receptor binding in atopic dermatitis is normal. Reduced cyclic AMP generation in atopic dermatitis PMN leukocytes would appear to be due to a defect distal to the beta adrenergic receptor itself.", "contents": "Beta adrenergic receptor binding on polymorphonuclear leukocytes in atopic dermatitis. It has been postulated that the patient with atopic dermatitis has defective beta adrenergic receptor function. However, a more generalized defect is suggested by the observation that cyclic AMP generation is diminished in these patients following stimulation with both isoproterenol and PGE1. To determine the nature of this abnormality, we measured beta adrenergic receptor binding directly on polymorphonuclear leukocyte membranes using the radiolabeled beta adrenergic antagonist (-) [3H]dihydroalprenolol (DHA). DHA binding was studied in 6 mild and 9 moderate-to-severe atopic dermatitis patients, and 8 normal controls using a subsaturating concentration of DHA (0.5 nM) to estimate receptor affinity and a saturating concentration of DHA (30 mM) to determine the total number of receptors per cell. No significant differences (p greater than .05) were found in the total number of receptors per PMN between the control population (805 +/- 95) and the mild atopic dermatitis patients (745 +/- 91) or the moderate to severe group (621 +/- 79). In addition, no significant differences in receptor affinity were found among any of the 3 study groups. These findings suggest that beta receptor binding in atopic dermatitis is normal. Reduced cyclic AMP generation in atopic dermatitis PMN leukocytes would appear to be due to a defect distal to the beta adrenergic receptor itself."}
{"id": "PMID:221595", "title": "Migration of epithelial cells in the small intestine of mice perorally infected with coxsackievirus B5.", "content": "The rate of cell migration in the small intestine during enteric viral infections has not been assessed previously. CD-1 mice (33 days old) were infected perorally with 1.0 X 10(8) plague-forming units of coxsackievirus B5 and 12 hr later were injected intraperitoneally with 2 micron Ci of [3H]thymidine/g of body weight. After 2, 12, 24, 48, 60, and 72 hr, mice were killed, and the small intestine was removed. Specimens obtained at each interval were examined by radioautography; similar specimens were titrated for virus by plaque assay in HeLa cells. In mice perorally infected with coxsackievirus B5, epithelial cells migrated from crypt to villus tip in 60 hr, as compared with 48 hr in uninfected control mice and 24 hr previously reported for mice perorally infected with enteric bacteria (e.g., Salmonella typhimurium). Virus was recovered from intestinal tissue, but no inflammatory response in the limina propria was apparent. These observations are consistent with previous report that substrate absorption rates may be altered during viral and bacterial enteric infection.", "contents": "Migration of epithelial cells in the small intestine of mice perorally infected with coxsackievirus B5. The rate of cell migration in the small intestine during enteric viral infections has not been assessed previously. CD-1 mice (33 days old) were infected perorally with 1.0 X 10(8) plague-forming units of coxsackievirus B5 and 12 hr later were injected intraperitoneally with 2 micron Ci of [3H]thymidine/g of body weight. After 2, 12, 24, 48, 60, and 72 hr, mice were killed, and the small intestine was removed. Specimens obtained at each interval were examined by radioautography; similar specimens were titrated for virus by plaque assay in HeLa cells. In mice perorally infected with coxsackievirus B5, epithelial cells migrated from crypt to villus tip in 60 hr, as compared with 48 hr in uninfected control mice and 24 hr previously reported for mice perorally infected with enteric bacteria (e.g., Salmonella typhimurium). Virus was recovered from intestinal tissue, but no inflammatory response in the limina propria was apparent. These observations are consistent with previous report that substrate absorption rates may be altered during viral and bacterial enteric infection."}
{"id": "PMID:221596", "title": "Simultaneous acute infections with hepatitis A and hepatitis B viruses in a chimpanzee.", "content": "The unexpected occurrence of a hepatitis B virus (HBV) infection in a chimpanzee experimentally inoculated with hepatitis A virus (HAV) provided an opportunity to examine the course of simultaneous acute infections with both agents. A chimpanzee inoculated intravenously with HAV developed elevated levels of aminotransferases in serum, detectable excretion of hepatitis A antigen in feces, and a marked antibody response to HAV. During the acute phase of this experimentally induced infection with HAV, the chimpanzee simultaneously developed an HBV infection. The latter was characterized by jaundice, a second increase in levels of aminotransferases in serum, and the appearance in serum of hepatitis B surface antigen (HBsAg), hepatitis B e antigen, antibody to hepatitis B core antigen, and, later, antibody to HBsAg. During the acute phase of both HAV and HBV infections, marked histopathologic inflammatory changes were observed in serial liver biopsy specimens. In this chimpanzee, the concurrent acute infection with both HAV and HBV occurred in association with marked liver damage.", "contents": "Simultaneous acute infections with hepatitis A and hepatitis B viruses in a chimpanzee. The unexpected occurrence of a hepatitis B virus (HBV) infection in a chimpanzee experimentally inoculated with hepatitis A virus (HAV) provided an opportunity to examine the course of simultaneous acute infections with both agents. A chimpanzee inoculated intravenously with HAV developed elevated levels of aminotransferases in serum, detectable excretion of hepatitis A antigen in feces, and a marked antibody response to HAV. During the acute phase of this experimentally induced infection with HAV, the chimpanzee simultaneously developed an HBV infection. The latter was characterized by jaundice, a second increase in levels of aminotransferases in serum, and the appearance in serum of hepatitis B surface antigen (HBsAg), hepatitis B e antigen, antibody to hepatitis B core antigen, and, later, antibody to HBsAg. During the acute phase of both HAV and HBV infections, marked histopathologic inflammatory changes were observed in serial liver biopsy specimens. In this chimpanzee, the concurrent acute infection with both HAV and HBV occurred in association with marked liver damage."}
{"id": "PMID:221597", "title": "Activation of reticuloendothelial cells following infection with murine cytomegalovirus.", "content": "Macrophage and reticuloendothelial system function was investigated in adult, female C3H mice during the course of a nonlethal infection with murine cytomegalovirus (MCMV). Peritoneal macrophages harvested from mice infected three to 21 days previously were tumoricidal in vitro for a syngeneic mammary tumor cell line and showed antiviral activity by suppressing replication of vaccinia virus in a fibroblast monolayer. In addition, macrophages harvested from animals on days 7 and 14 after MCMV infection manifested augmented phagocytosis of yeast particles in vitro. Furthermore, enhanced levels of chemiluminescence were emitted during phagocytosis of zymosan particles by macrophages harvested on days 3 and 7 after MCMV infection. Finally, enhanced protection against Listeria monocytogenes was demonstrated in mice on days 7, 14, and 21 after MCMV infection. These findings support the concept of activation of the reticuloendothelial system during viral infection.", "contents": "Activation of reticuloendothelial cells following infection with murine cytomegalovirus. Macrophage and reticuloendothelial system function was investigated in adult, female C3H mice during the course of a nonlethal infection with murine cytomegalovirus (MCMV). Peritoneal macrophages harvested from mice infected three to 21 days previously were tumoricidal in vitro for a syngeneic mammary tumor cell line and showed antiviral activity by suppressing replication of vaccinia virus in a fibroblast monolayer. In addition, macrophages harvested from animals on days 7 and 14 after MCMV infection manifested augmented phagocytosis of yeast particles in vitro. Furthermore, enhanced levels of chemiluminescence were emitted during phagocytosis of zymosan particles by macrophages harvested on days 3 and 7 after MCMV infection. Finally, enhanced protection against Listeria monocytogenes was demonstrated in mice on days 7, 14, and 21 after MCMV infection. These findings support the concept of activation of the reticuloendothelial system during viral infection."}
{"id": "PMID:221599", "title": "[Studies on the refractory coating materials for preventing scale formation (author's transl)].", "content": "In casting of high-fusing alloys such as cobalt-chrome and nickle-chrome alloys, the reaction between the investing mold and high-fusing molten alloys suffers the disadvantage of the scale formation. The various coating materials are used to prevent the scale formation. The experiments have been carried out to prove the effectiveness of seven commercialized coating materials. And the reaction between the coating materials and high-fusing molten alloys was analyzed by X-ray diffractometer. Results were as follows: 1) The refractory compositions of seven commercialized coating materials were composed of alpha-quartz (SiO2), zircon (ZrSiO4) and zirconium oxide (ZrO2). 2) Dainainvest (Ohara) mainly containing zircon indicated the reduction in surface roughness due to coating. Although zircon was slightly observed on the cast surface, the product of reaction was not detected. 3) Liquid investment (Nobilium) and Paint investment (Shofu) having about equal amounts of alpha-quartz and zircon showed as reduction in surface roughness as Dainainvest. The product of reaction was not observed and the cast surface was smooth. 4) Quick request (Shiken), Pre-coat (Niranium) and Ethymay B (Kamemizu) composed of alpha-quartz had not appreciably effectiveness. The cast surface was rough due to production of picrochromite (MgCr2O4) and eskolaite (Cr2O3)in the reaction between molten alloys and coating materials. 5) Hi-coat with zirconium oxide did not point out the advantage in spite of high refractory composition and showed little reduction in surface roughness due to coating.", "contents": "[Studies on the refractory coating materials for preventing scale formation (author's transl)]. In casting of high-fusing alloys such as cobalt-chrome and nickle-chrome alloys, the reaction between the investing mold and high-fusing molten alloys suffers the disadvantage of the scale formation. The various coating materials are used to prevent the scale formation. The experiments have been carried out to prove the effectiveness of seven commercialized coating materials. And the reaction between the coating materials and high-fusing molten alloys was analyzed by X-ray diffractometer. Results were as follows: 1) The refractory compositions of seven commercialized coating materials were composed of alpha-quartz (SiO2), zircon (ZrSiO4) and zirconium oxide (ZrO2). 2) Dainainvest (Ohara) mainly containing zircon indicated the reduction in surface roughness due to coating. Although zircon was slightly observed on the cast surface, the product of reaction was not detected. 3) Liquid investment (Nobilium) and Paint investment (Shofu) having about equal amounts of alpha-quartz and zircon showed as reduction in surface roughness as Dainainvest. The product of reaction was not observed and the cast surface was smooth. 4) Quick request (Shiken), Pre-coat (Niranium) and Ethymay B (Kamemizu) composed of alpha-quartz had not appreciably effectiveness. The cast surface was rough due to production of picrochromite (MgCr2O4) and eskolaite (Cr2O3)in the reaction between molten alloys and coating materials. 5) Hi-coat with zirconium oxide did not point out the advantage in spite of high refractory composition and showed little reduction in surface roughness due to coating."}
{"id": "PMID:221600", "title": "[Preparation of hard crown and bridge resin without PMMA powder (author's transl)].", "content": "Elimination of PMMA powder to prepare better hard crown and bridge resin had been pointed out by the authors even though polyfunctional methacrylates were used. Application of hydrophobic coloidal silica instead of PMMA pearl with triethyleneglycol dimethacrylate and Bis-GMA was studied. Polyermization was carried out in the hot air stream at 120 degrees approximately 130 degrees C or in a pressure vessel at 4.5 kg/cm2 gauge, 100 degrees C. Mechanical properties, brinell hardness, compressive strength, an amount of water sorption, comparative average abrasion loss depth with those of PMMA, were measured. They were improved very much by this new system.", "contents": "[Preparation of hard crown and bridge resin without PMMA powder (author's transl)]. Elimination of PMMA powder to prepare better hard crown and bridge resin had been pointed out by the authors even though polyfunctional methacrylates were used. Application of hydrophobic coloidal silica instead of PMMA pearl with triethyleneglycol dimethacrylate and Bis-GMA was studied. Polyermization was carried out in the hot air stream at 120 degrees approximately 130 degrees C or in a pressure vessel at 4.5 kg/cm2 gauge, 100 degrees C. Mechanical properties, brinell hardness, compressive strength, an amount of water sorption, comparative average abrasion loss depth with those of PMMA, were measured. They were improved very much by this new system."}
{"id": "PMID:221602", "title": "Quantification of the hepatic contribution to the catabolism of high density lipoproteins in rats.", "content": "Isolated rat livers were perfused for four hours in a recirculating system containing washed rat erythrocytes. Biologically screened radioiodinated rat high density lipoproteins (1.090 < d < 1.21 g/ml) were added to the perfusate with different amounts of whole serum to supply unlabeled rat high density lipoproteins. The protein moiety of the lipoprotein contained more than 95% of the radioiodine. The fraction of apolipoprotein mass degraded during the perfusion was quantified by the linear increment of non-protein-bound radioiodine in the perfusate, corrected for the increment observed during recirculation of the perfusate in the absence of a liver. The small amount of (131)I secreted into bile was added to calculate the fractional catabolic rate. The fractional catabolic rate ranged from 0.22 to 0.63% per hour in 12 experiments and was inversely related to the size of the perfusate pool of high density apolipoprotein. The absolute catabolic rate of high density apolipoprotein (fractional catabolic rate x pool size) in three livers in which the concentration of rat HDL in the perfusate approximated that in intact rats was 69.5 +/- 10.4 micro g hr(-1) (mean +/- SD). The rate of disappearance of cholesteryl esters of rat high density lipoproteins (labeled biologically by injecting donor rats with [5-(3)H]mevalonic acid) from the liver perfusate did not exceed that of the apoprotein component. These rates were compared with catabolic rates for rat high density lipoproteins in intact rats. Fractional catabolic rate in vivo, obtained by multicompartmental analysis of the disappearance curve of (131)I-high density apolipoprotein from blood plasma, was 11.9 +/- 1.3% hr(-1) (mean +/- SD). Total catabolic rate in vivo (fractional catabolic rate x intravascular pool of high density apolipoprotein) was 986 +/- 145 micro g hr(-1) (mean +/- SD). The results suggest that only a small fraction of high density lipoproteins in blood plasma of rats is degraded directly by the liver.-Sigurdsson, G., S-P. Noel, and R. J. Havel. Quantification of the hepatic contribution to the catabolism of high density lipoproteins in rats.", "contents": "Quantification of the hepatic contribution to the catabolism of high density lipoproteins in rats. Isolated rat livers were perfused for four hours in a recirculating system containing washed rat erythrocytes. Biologically screened radioiodinated rat high density lipoproteins (1.090 < d < 1.21 g/ml) were added to the perfusate with different amounts of whole serum to supply unlabeled rat high density lipoproteins. The protein moiety of the lipoprotein contained more than 95% of the radioiodine. The fraction of apolipoprotein mass degraded during the perfusion was quantified by the linear increment of non-protein-bound radioiodine in the perfusate, corrected for the increment observed during recirculation of the perfusate in the absence of a liver. The small amount of (131)I secreted into bile was added to calculate the fractional catabolic rate. The fractional catabolic rate ranged from 0.22 to 0.63% per hour in 12 experiments and was inversely related to the size of the perfusate pool of high density apolipoprotein. The absolute catabolic rate of high density apolipoprotein (fractional catabolic rate x pool size) in three livers in which the concentration of rat HDL in the perfusate approximated that in intact rats was 69.5 +/- 10.4 micro g hr(-1) (mean +/- SD). The rate of disappearance of cholesteryl esters of rat high density lipoproteins (labeled biologically by injecting donor rats with [5-(3)H]mevalonic acid) from the liver perfusate did not exceed that of the apoprotein component. These rates were compared with catabolic rates for rat high density lipoproteins in intact rats. Fractional catabolic rate in vivo, obtained by multicompartmental analysis of the disappearance curve of (131)I-high density apolipoprotein from blood plasma, was 11.9 +/- 1.3% hr(-1) (mean +/- SD). Total catabolic rate in vivo (fractional catabolic rate x intravascular pool of high density apolipoprotein) was 986 +/- 145 micro g hr(-1) (mean +/- SD). The results suggest that only a small fraction of high density lipoproteins in blood plasma of rats is degraded directly by the liver.-Sigurdsson, G., S-P. Noel, and R. J. Havel. Quantification of the hepatic contribution to the catabolism of high density lipoproteins in rats."}
{"id": "PMID:221603", "title": "Translation in vivo and in vitro of proteins resembling apoproteins of rat plasma very low density lipoprotein.", "content": "Antibodies raised against rat plasma apoVLDL and a purified fraction of arginine-rich peptides (ARP) were labeled with Na125I and were shown to bind to polyribosomes isolated from rat liver. Antibody fractions enriched by selective affinity chromatography exhibited increased levels of binding to polysomes. Anti-apoVLDL immunoreactivity was further resolved into anti-ARP and anti apoB components, each reactive with a distinct polysome population. Binding was specific for rat polysomes, and was directed toward nascent polypeptide chains. About 2% of normal rat liver polysomes were recovered by indirect immunoprecipitation with anti-apoVLDL. Ribonucleic acid (RNA) extracted from this immunoprecipitate contained species with polyadenylate (poly[A] sequences characteristic of eukaryotic messenger RNA (mRNA). These species, purified by affinity chromatography on poly(U)-Sepharose, stimulated the in vitro synthesis of immunoprecipitable apoVLDL-like proteins by about 17-fold when compared to unfractionated rat liver mRNA. Most of the in vitro translation products precipitated by purified anti-ARP migrated identically on polyacrylamide gel electrophoresis with unlabeled purified ARP. Some implications of these findings with respect to plasma VLDL biosynthesis are discussed.", "contents": "Translation in vivo and in vitro of proteins resembling apoproteins of rat plasma very low density lipoprotein. Antibodies raised against rat plasma apoVLDL and a purified fraction of arginine-rich peptides (ARP) were labeled with Na125I and were shown to bind to polyribosomes isolated from rat liver. Antibody fractions enriched by selective affinity chromatography exhibited increased levels of binding to polysomes. Anti-apoVLDL immunoreactivity was further resolved into anti-ARP and anti apoB components, each reactive with a distinct polysome population. Binding was specific for rat polysomes, and was directed toward nascent polypeptide chains. About 2% of normal rat liver polysomes were recovered by indirect immunoprecipitation with anti-apoVLDL. Ribonucleic acid (RNA) extracted from this immunoprecipitate contained species with polyadenylate (poly[A] sequences characteristic of eukaryotic messenger RNA (mRNA). These species, purified by affinity chromatography on poly(U)-Sepharose, stimulated the in vitro synthesis of immunoprecipitable apoVLDL-like proteins by about 17-fold when compared to unfractionated rat liver mRNA. Most of the in vitro translation products precipitated by purified anti-ARP migrated identically on polyacrylamide gel electrophoresis with unlabeled purified ARP. Some implications of these findings with respect to plasma VLDL biosynthesis are discussed."}
{"id": "PMID:221604", "title": "Characterization of a model of dietary-induced hypertriglyceridemia in young, nonobese rats.", "content": "Healthy, nonobese, young rats developed hypertriglyceridemia (mean triglyceride levels of 250 mg/dl) following consumption of a sucrose-lard diet. The hypertriglyceridemia was apparent three days after start of the diet and persisted throughout the 4-week experimental period. Body weight, liver weight, and serum glucose levels were similar in animals eating either the sucrose-lard diet or standard rat chow. On the other hand, serum free fatty acid levels were slightly increased and serum insulin levels were substantially increased in animals eating the sucrose-lard diet. Determination of very low density lipoprotein turnover revealed that total triglyceride secretion in rats eating the sucrose-lard diet was significantly (P < 0.01) increased over that of rats eating standard chow. Direct measurement of hepatic and intestinal very low density lipoprotein secretion indicated that the observed rise in total triglyceride secretion was secondary to increased secretion of very low density lipoproteins by the liver. Finally, lipoprotein lipase activity of adipose tissue from rats eating the sucrose-lard diet was equal to, or greater than (depending upon sampling time), the activity of the enzyme from adipose tissue of rats eating the control diet. These data indicate that young, nonobese, rats develop hypertriglyceridemia when they ingest a sucrose-lard diet, and that the rise in plasma triglyceride levels results from an increase in hepatic very low density lipoprotein secretion. The dietary-induced hypertriglyceridemia is associated with elevated serum insulin levels, and, as such, may provide a useful animal model to use in studies aimed at defining the pathogenesis of endogenous hypertriglyceridemia in man.-Reaven, G. M., T. R. Risser, Y-D. I. Chen, and E. P. Reaven. Characterization of a model of dietary-induced hypertriglyceridemia in young, nonobese rats.", "contents": "Characterization of a model of dietary-induced hypertriglyceridemia in young, nonobese rats. Healthy, nonobese, young rats developed hypertriglyceridemia (mean triglyceride levels of 250 mg/dl) following consumption of a sucrose-lard diet. The hypertriglyceridemia was apparent three days after start of the diet and persisted throughout the 4-week experimental period. Body weight, liver weight, and serum glucose levels were similar in animals eating either the sucrose-lard diet or standard rat chow. On the other hand, serum free fatty acid levels were slightly increased and serum insulin levels were substantially increased in animals eating the sucrose-lard diet. Determination of very low density lipoprotein turnover revealed that total triglyceride secretion in rats eating the sucrose-lard diet was significantly (P < 0.01) increased over that of rats eating standard chow. Direct measurement of hepatic and intestinal very low density lipoprotein secretion indicated that the observed rise in total triglyceride secretion was secondary to increased secretion of very low density lipoproteins by the liver. Finally, lipoprotein lipase activity of adipose tissue from rats eating the sucrose-lard diet was equal to, or greater than (depending upon sampling time), the activity of the enzyme from adipose tissue of rats eating the control diet. These data indicate that young, nonobese, rats develop hypertriglyceridemia when they ingest a sucrose-lard diet, and that the rise in plasma triglyceride levels results from an increase in hepatic very low density lipoprotein secretion. The dietary-induced hypertriglyceridemia is associated with elevated serum insulin levels, and, as such, may provide a useful animal model to use in studies aimed at defining the pathogenesis of endogenous hypertriglyceridemia in man.-Reaven, G. M., T. R. Risser, Y-D. I. Chen, and E. P. Reaven. Characterization of a model of dietary-induced hypertriglyceridemia in young, nonobese rats."}
{"id": "PMID:221605", "title": "Regulation of plasma lecithin:cholesterol acyltransferase in man. III. Role of high density lipoprotein cholesteryl esters in the activating effect of a high-fat test meal.", "content": "Plasma lecithin:cholesterol acyltransferase (LCAT) activity is increased during the clearance phase of alimentary lipemia induced by a high-fat test meal in normal subjects. Ultracentrifugal fractionation of high density lipoproteins (HDL) into HDL(2), HDL(3), and very high density (VHD) subfractions followed by analyses of lipid and protein components has been accomplished at intervals during alimentary lipemia to seek associations with enzyme changes. HDL(2) lipids and protein increased substantially, characterized primarily by enrichment with lecithin. HDL(3), which contain the main LCAT substrates, revealed increased triglycerides and generally reduced cholesteryl esters which were reciprocally correlated, demonstrating a phenomenon previously observed in vitro by others. Both changes correlated with LCAT activation, but partial correlation analysis indicated that ester content is primarily related to triglycerides rather than LCAT activity. The VHD cholesteryl esters and lysolecithin were also reduced. Plasma incubation experiments with inactivated LCAT showed that alimentary lipemic very low density lipoproteins (VLDL) could reduce levels of cholesteryl esters in HDL by a nonenzymatic mechanism. In vitro substitution of lipemic VLDL for postabsorptive VLDL resulted in enhanced reduction of cholesteryl esters in HDL(3) and VDH, but not in HDL(2), during incubation. Nevertheless, augmentation of LCAT activity did not result, indicating that cholesteryl ester removal from substrate lipoproteins is an unlikely explanation for activation. Since VHD and HDL(3), which contain the most active LCAT substrates, were also most clearly involved in transfers of esters to VLDL and low density lipoproteins, the suggestion that LCAT product lipoproteins are preferentially involved in nonenzymatic transfer and exchange is made. The main determinant of ester transfer, however, appears to be the level of VLDL, both in vitro and in vivo. Rose, H. G., and J. Juliano. Regulation of plasma lecithin: cholesteryl acyltransferase in man. III. Role of high density lipoprotein cholesteryl esters in the activating effect of a high-fat test meal.", "contents": "Regulation of plasma lecithin:cholesterol acyltransferase in man. III. Role of high density lipoprotein cholesteryl esters in the activating effect of a high-fat test meal. Plasma lecithin:cholesterol acyltransferase (LCAT) activity is increased during the clearance phase of alimentary lipemia induced by a high-fat test meal in normal subjects. Ultracentrifugal fractionation of high density lipoproteins (HDL) into HDL(2), HDL(3), and very high density (VHD) subfractions followed by analyses of lipid and protein components has been accomplished at intervals during alimentary lipemia to seek associations with enzyme changes. HDL(2) lipids and protein increased substantially, characterized primarily by enrichment with lecithin. HDL(3), which contain the main LCAT substrates, revealed increased triglycerides and generally reduced cholesteryl esters which were reciprocally correlated, demonstrating a phenomenon previously observed in vitro by others. Both changes correlated with LCAT activation, but partial correlation analysis indicated that ester content is primarily related to triglycerides rather than LCAT activity. The VHD cholesteryl esters and lysolecithin were also reduced. Plasma incubation experiments with inactivated LCAT showed that alimentary lipemic very low density lipoproteins (VLDL) could reduce levels of cholesteryl esters in HDL by a nonenzymatic mechanism. In vitro substitution of lipemic VLDL for postabsorptive VLDL resulted in enhanced reduction of cholesteryl esters in HDL(3) and VDH, but not in HDL(2), during incubation. Nevertheless, augmentation of LCAT activity did not result, indicating that cholesteryl ester removal from substrate lipoproteins is an unlikely explanation for activation. Since VHD and HDL(3), which contain the most active LCAT substrates, were also most clearly involved in transfers of esters to VLDL and low density lipoproteins, the suggestion that LCAT product lipoproteins are preferentially involved in nonenzymatic transfer and exchange is made. The main determinant of ester transfer, however, appears to be the level of VLDL, both in vitro and in vivo. Rose, H. G., and J. Juliano. Regulation of plasma lecithin: cholesteryl acyltransferase in man. III. Role of high density lipoprotein cholesteryl esters in the activating effect of a high-fat test meal."}
{"id": "PMID:221606", "title": "A comparison of delipidated sera used in studies of sterol synthesis by human mononuclear leukocytes.", "content": "Sterol synthesis in human mononuclear leukocytes is stimulated by delipidated serum. Synthesis in media containing serum delipidated by three different methods is compared. Significant differences between subjects are shown and the differences are maximized by measuring synthesis in serum delipidated by extraction with butanol-diisopropyl ether 40:60 and diethyl ether.", "contents": "A comparison of delipidated sera used in studies of sterol synthesis by human mononuclear leukocytes. Sterol synthesis in human mononuclear leukocytes is stimulated by delipidated serum. Synthesis in media containing serum delipidated by three different methods is compared. Significant differences between subjects are shown and the differences are maximized by measuring synthesis in serum delipidated by extraction with butanol-diisopropyl ether 40:60 and diethyl ether."}
{"id": "PMID:221609", "title": "The in vitro effects of Bordetella pertussis lymphocytosis-promoting factor on murine lymphocytes. III. B-cell dependence for T-cell proliferation.", "content": "The nature of the helper lymphocytes in lymphocytosis-promoting factor (LPF)-induced proliferation was explored. Removal of macrophages from adherent splenocytes by either carbonyl-iron incubation or passage through Sephadex G-10 columns did not affect their synergistic function. Nor did cytolysis with Thy-1.2 antiserum and complement. The helper cells were found to be surface immunoglobulin-positive (sIg+) because they are retained by anti-Ig columns, susceptible to lysis by rabbit anti-mouse immunoglobulin and complement, and occurred in the sIg+ fractions of splenocytes after separation on the fluorescence-activated cell sorter. Further delineation of the surface markers on helper cells showed that complement receptors are not the determining marker for synergistic function. The requirement for B-helper cells in the stimulation of T lymphocytes by LPF is unique for a mouse of T-cell mitogen.", "contents": "The in vitro effects of Bordetella pertussis lymphocytosis-promoting factor on murine lymphocytes. III. B-cell dependence for T-cell proliferation. The nature of the helper lymphocytes in lymphocytosis-promoting factor (LPF)-induced proliferation was explored. Removal of macrophages from adherent splenocytes by either carbonyl-iron incubation or passage through Sephadex G-10 columns did not affect their synergistic function. Nor did cytolysis with Thy-1.2 antiserum and complement. The helper cells were found to be surface immunoglobulin-positive (sIg+) because they are retained by anti-Ig columns, susceptible to lysis by rabbit anti-mouse immunoglobulin and complement, and occurred in the sIg+ fractions of splenocytes after separation on the fluorescence-activated cell sorter. Further delineation of the surface markers on helper cells showed that complement receptors are not the determining marker for synergistic function. The requirement for B-helper cells in the stimulation of T lymphocytes by LPF is unique for a mouse of T-cell mitogen."}
{"id": "PMID:221610", "title": "Association of circulating retroviral gp70-anti-gp70 immune complexes with murine systemic lupus erythematosus.", "content": "Endogenous retroviral gp70 was investigated as a participant in the pathogenesis of a lupus-like disease that spontaneously develops in four kinds of mice (NZB, NZB x W MRL/1, and male BXSB). Sera from these strains contain a heavy form of gp 70 that varies in sedimentation rates from 9S to 19S in sucrose density gradient analysis and appears with the onset of disease and persists throughout its course. Immunologically normal strains of mice do not develop rapidly sedimenting gp70 by 8-10 mo of life. The fact that the heavy gp70 is selectively absorbed with anti-IgG antibodies or with Staphylococcus aureus protein A suggests that it is complexed with antibodies. The incidence and quantities of these gp70 ICs rise with the progression of disease in all strains with lupus. These findings suggest that Ig-complexed heavy gp70 may be involved in the pathogenesis of glomerulonephritis of mice with SLE.", "contents": "Association of circulating retroviral gp70-anti-gp70 immune complexes with murine systemic lupus erythematosus. Endogenous retroviral gp70 was investigated as a participant in the pathogenesis of a lupus-like disease that spontaneously develops in four kinds of mice (NZB, NZB x W MRL/1, and male BXSB). Sera from these strains contain a heavy form of gp 70 that varies in sedimentation rates from 9S to 19S in sucrose density gradient analysis and appears with the onset of disease and persists throughout its course. Immunologically normal strains of mice do not develop rapidly sedimenting gp70 by 8-10 mo of life. The fact that the heavy gp70 is selectively absorbed with anti-IgG antibodies or with Staphylococcus aureus protein A suggests that it is complexed with antibodies. The incidence and quantities of these gp70 ICs rise with the progression of disease in all strains with lupus. These findings suggest that Ig-complexed heavy gp70 may be involved in the pathogenesis of glomerulonephritis of mice with SLE."}
{"id": "PMID:221608", "title": "Plasma levels of immunoreactive parathyroid hormone in dogs chronically exposed to low levels of cadmium chloride.", "content": "A previous report had suggested that chronic cadmium intoxication interfered with calcium accumulation in bone and suggested that the mechanism may be a parathyroid-induced bone resorption. We measured C-terminal parathyroid hormone levels in the blood of four male standardized research beagles chronically exposed during 6 months to 25 ppm cadmium chloride in their drinking water while at the same time we performed measurements of the parameters of haversian bone remodelling activity. We failed to demonstrate any statistically significant difference in levels of this hormone in the experimental dogs before or during the exposure, or between samples obtained from the experimental dogs at the end of their period of exposure and normal untreated control dogs from the same colony. We conclude that in the early stages of chronic cadmium intoxication before there is evidence suggestive of intestinal or renal malfunction that may secondarily involve the parathyroid glands, the alteration observed in haversian bone remodelling rates is not mediated through abnormalities of function of the parathyroid glands.", "contents": "Plasma levels of immunoreactive parathyroid hormone in dogs chronically exposed to low levels of cadmium chloride. A previous report had suggested that chronic cadmium intoxication interfered with calcium accumulation in bone and suggested that the mechanism may be a parathyroid-induced bone resorption. We measured C-terminal parathyroid hormone levels in the blood of four male standardized research beagles chronically exposed during 6 months to 25 ppm cadmium chloride in their drinking water while at the same time we performed measurements of the parameters of haversian bone remodelling activity. We failed to demonstrate any statistically significant difference in levels of this hormone in the experimental dogs before or during the exposure, or between samples obtained from the experimental dogs at the end of their period of exposure and normal untreated control dogs from the same colony. We conclude that in the early stages of chronic cadmium intoxication before there is evidence suggestive of intestinal or renal malfunction that may secondarily involve the parathyroid glands, the alteration observed in haversian bone remodelling rates is not mediated through abnormalities of function of the parathyroid glands."}
{"id": "PMID:221611", "title": "Mechanism of rejection of virus persistently infected tumor cells by athymic nude mice.", "content": "Cell lines known to be tumorigenic in the nude mouse were modified by rendering them persistently infected (P.I.) with a variety of RNA viruses, including measles, mumps, vesicular stomatitis virus, and influenza. Although as few as 100 HeLa or BHK cells produced tumors in 100% of nude mice, as many as 2 x 10(7) of the same cells P.I. with viruses failed to produce tumors. An active host response responsible for restricting the growth of the P.I. cells was suggested by the findings of marked mononuclear cell infiltrates at the inoculation sites and the inability of irradiated nude mice to reject them. An analysis of the in vitro cytotoxic activity of spleen cells from normal nude mice indicated that: (a) P.I. cell lines, but not uninfected cell lines, were susceptible to spontaneous cytotoxicity; (b) in vivo inoculation of P.I. lines induced an enhanced cytotoxic activity for P.I. targets in vitro, and this induction was not specific either for inducing virus or cell line; and (c) the effector cell had the characteristics for natural killer (NK) cells. Although the specificity of recognition of the various P.I. cell lines remains unclear, cold competition experiments indicated that blocking the killing of one P.I. cell line, e.g. HeLa-measles, could be achieved only by unlabeled homologous cells, i.e. HeLa-measles, and not by uninfected cells or other P.I. lines. A variant subline of BHK cells P.I. with VSV was selected for its ability to withstand the rejection process in nude mice. These cells formed metastatic and invasive tumors in nude mice. Although they were the most potent inducers in vivo of NK cell activity against various P.I. targets, they were the most resistant of the P.I. lines to NK cell cytotoxicity in vitro. In this system there was a good correlation between tumor rejection in vivo and susceptibility to NK cells in vitro. The present results suggest that NK cells may play a significant role in both rejection of tumor cells, and in resistance to viruses, particularly persistent infections.", "contents": "Mechanism of rejection of virus persistently infected tumor cells by athymic nude mice. Cell lines known to be tumorigenic in the nude mouse were modified by rendering them persistently infected (P.I.) with a variety of RNA viruses, including measles, mumps, vesicular stomatitis virus, and influenza. Although as few as 100 HeLa or BHK cells produced tumors in 100% of nude mice, as many as 2 x 10(7) of the same cells P.I. with viruses failed to produce tumors. An active host response responsible for restricting the growth of the P.I. cells was suggested by the findings of marked mononuclear cell infiltrates at the inoculation sites and the inability of irradiated nude mice to reject them. An analysis of the in vitro cytotoxic activity of spleen cells from normal nude mice indicated that: (a) P.I. cell lines, but not uninfected cell lines, were susceptible to spontaneous cytotoxicity; (b) in vivo inoculation of P.I. lines induced an enhanced cytotoxic activity for P.I. targets in vitro, and this induction was not specific either for inducing virus or cell line; and (c) the effector cell had the characteristics for natural killer (NK) cells. Although the specificity of recognition of the various P.I. cell lines remains unclear, cold competition experiments indicated that blocking the killing of one P.I. cell line, e.g. HeLa-measles, could be achieved only by unlabeled homologous cells, i.e. HeLa-measles, and not by uninfected cells or other P.I. lines. A variant subline of BHK cells P.I. with VSV was selected for its ability to withstand the rejection process in nude mice. These cells formed metastatic and invasive tumors in nude mice. Although they were the most potent inducers in vivo of NK cell activity against various P.I. targets, they were the most resistant of the P.I. lines to NK cell cytotoxicity in vitro. In this system there was a good correlation between tumor rejection in vivo and susceptibility to NK cells in vitro. The present results suggest that NK cells may play a significant role in both rejection of tumor cells, and in resistance to viruses, particularly persistent infections."}
{"id": "PMID:221612", "title": "Expression of xenotropic murine leukemia viruses as cell-surface gp70 in genetic crosses between strains DBA/2 and C57BL/6.", "content": "Flow microfluorometry was used to assess levels of xenotropic murine leukemia virus envelope-related cell-surface antigens (XenCSA) expressed on lymphocytes of mice derived from crosses between C57BL/6 (B6) and DBA/2 (D2); 24 recombinant inbred strains (BXD RIs) and 62 backcross mice were studied. The results suggest that XenCSA expression is affected by more than one gene but that the predominant influence is exerted by a single semidominant gene apparently located on chromosome 4 at or in close proximity to the Fv-1 locus. Studies of spontaneous virus production in B6D2F1 X D2 mice suggest that this locus may also affect production by spleen cells of xenotropic MuLV registering in a fluorescent antibody assay of mink lung cells.", "contents": "Expression of xenotropic murine leukemia viruses as cell-surface gp70 in genetic crosses between strains DBA/2 and C57BL/6. Flow microfluorometry was used to assess levels of xenotropic murine leukemia virus envelope-related cell-surface antigens (XenCSA) expressed on lymphocytes of mice derived from crosses between C57BL/6 (B6) and DBA/2 (D2); 24 recombinant inbred strains (BXD RIs) and 62 backcross mice were studied. The results suggest that XenCSA expression is affected by more than one gene but that the predominant influence is exerted by a single semidominant gene apparently located on chromosome 4 at or in close proximity to the Fv-1 locus. Studies of spontaneous virus production in B6D2F1 X D2 mice suggest that this locus may also affect production by spleen cells of xenotropic MuLV registering in a fluorescent antibody assay of mink lung cells."}
{"id": "PMID:221613", "title": "The in vitro effects of Bordetella pertussis lymphocytosis-promoting factor on murine lymphocytes. IV. Generation, characterization, and specificity of cytotoxic lymphocytes.", "content": "Cytotoxic effector lymphocytes were induced in cultures of mouse spleen or lymph node cells by lymphocytosis promoting factor (LPF). The LPF-activated cytotoxic cells: (a) were not generated unless proliferation occurred; (b) sedimented in the lighter density fraction of a bovine serum albumin gradient; (c) were large, blast-like cells; and (d) were lysed by Thy-1.2 antiserum plus complement and, therefore, were T cells. Neither LPF alone nor supernates from stimulated cultures were cytotoxic. Unlike the situation with concanavalin A and phytohemagglutinin P, LPF-stimulated cytotoxic effector lymphocytes required no further addition of mitogen for maximal cytotoxicity. The effector cells displayed specificity, destroying only allogeneic but not syngeneic normal cells; in the case of tumor cells, both allogeneic and syngeneic cells werelysed in the absence of added mitogen. The reason for differentiated cytotoxicity toward syngeneic tumor and normal cells is not clear but may have some relevance to in vivo tumor rejection initiated by Bordetella pertussis.", "contents": "The in vitro effects of Bordetella pertussis lymphocytosis-promoting factor on murine lymphocytes. IV. Generation, characterization, and specificity of cytotoxic lymphocytes. Cytotoxic effector lymphocytes were induced in cultures of mouse spleen or lymph node cells by lymphocytosis promoting factor (LPF). The LPF-activated cytotoxic cells: (a) were not generated unless proliferation occurred; (b) sedimented in the lighter density fraction of a bovine serum albumin gradient; (c) were large, blast-like cells; and (d) were lysed by Thy-1.2 antiserum plus complement and, therefore, were T cells. Neither LPF alone nor supernates from stimulated cultures were cytotoxic. Unlike the situation with concanavalin A and phytohemagglutinin P, LPF-stimulated cytotoxic effector lymphocytes required no further addition of mitogen for maximal cytotoxicity. The effector cells displayed specificity, destroying only allogeneic but not syngeneic normal cells; in the case of tumor cells, both allogeneic and syngeneic cells werelysed in the absence of added mitogen. The reason for differentiated cytotoxicity toward syngeneic tumor and normal cells is not clear but may have some relevance to in vivo tumor rejection initiated by Bordetella pertussis."}
{"id": "PMID:221614", "title": "Tumors induced by murine sarcoma virus contain precursor cells capable of generating tumor-specific cytolytic T lymphocytes.", "content": "Leukocyte fractions extracted from the tumor mass and the lymphoid organs of C57BL/6 (B6) mice carrying murine sarcoma virus-induced tumors contained primed cytolytic T-lymphocyte (CTL) precursor cells, in addition to active cytotoxic T cells. These leukocyte fractions gave a secondary response when stimulated in vitro with syngeneic tumor cells, generating large numbers of specific CTL. The activity of these CTL (H-2b) was apparently H-2-restricted, because it was ineffective on tumor targets bearing strongly cross-reacting tumor-specific antigens but with the H-2d haplotype. Furthermore, only H-2b cells bearing the Friend, Moloney, Rauscher-associated antigen, such as Rauscher leukemia virus-induced RBL-5 cells and Friend leukemia virus-induced HFL/b cells, were lysed efficiently. B male GV cells (H-2b cells induced by Gross leukemia virus) were not affected by the same CTL. We propose the existence of a dynamic state involving the migration of primed CTL precursor cells between the lymphoid organs and the tumor mass, as well as the differentiation of these precursor cells within the tumor mass into highly specific CTL.", "contents": "Tumors induced by murine sarcoma virus contain precursor cells capable of generating tumor-specific cytolytic T lymphocytes. Leukocyte fractions extracted from the tumor mass and the lymphoid organs of C57BL/6 (B6) mice carrying murine sarcoma virus-induced tumors contained primed cytolytic T-lymphocyte (CTL) precursor cells, in addition to active cytotoxic T cells. These leukocyte fractions gave a secondary response when stimulated in vitro with syngeneic tumor cells, generating large numbers of specific CTL. The activity of these CTL (H-2b) was apparently H-2-restricted, because it was ineffective on tumor targets bearing strongly cross-reacting tumor-specific antigens but with the H-2d haplotype. Furthermore, only H-2b cells bearing the Friend, Moloney, Rauscher-associated antigen, such as Rauscher leukemia virus-induced RBL-5 cells and Friend leukemia virus-induced HFL/b cells, were lysed efficiently. B male GV cells (H-2b cells induced by Gross leukemia virus) were not affected by the same CTL. We propose the existence of a dynamic state involving the migration of primed CTL precursor cells between the lymphoid organs and the tumor mass, as well as the differentiation of these precursor cells within the tumor mass into highly specific CTL."}
{"id": "PMID:221619", "title": "Systemic lupus erythematosus clinically resembling multiple sclerosis and with unusual pathological and ultrastructural features.", "content": "A case of systemic lupus erythematosus is described which clinically resembled multiple sclerosis and in which the lesions were restricted to the central nervous system. The necropsy findings of vascular thickening and necrosis in the spinal cord and in a posterior nerve root explain the main clinical abnormalities. Clinical signs of the terminal peritonitis secondary to cholecystitis were absent or minimised probably because of the steroid therapy and spinal cord necrosis. Primary demyelination was not demonstrated though electronmicroscopy revealed lattice fibrillar inclusions within a few myelin sheaths. An unusual ultrastructural feature was the finding of \"rod-shaped tubular bodies\" in large numbers in the endothelial cells of cerebral blood vessels. The incidence and morphology of these organelles are compared with those of the intracisternal tubuloreticular structures (TRS) commonly found in systemic lupus erythematosus.", "contents": "Systemic lupus erythematosus clinically resembling multiple sclerosis and with unusual pathological and ultrastructural features. A case of systemic lupus erythematosus is described which clinically resembled multiple sclerosis and in which the lesions were restricted to the central nervous system. The necropsy findings of vascular thickening and necrosis in the spinal cord and in a posterior nerve root explain the main clinical abnormalities. Clinical signs of the terminal peritonitis secondary to cholecystitis were absent or minimised probably because of the steroid therapy and spinal cord necrosis. Primary demyelination was not demonstrated though electronmicroscopy revealed lattice fibrillar inclusions within a few myelin sheaths. An unusual ultrastructural feature was the finding of \"rod-shaped tubular bodies\" in large numbers in the endothelial cells of cerebral blood vessels. The incidence and morphology of these organelles are compared with those of the intracisternal tubuloreticular structures (TRS) commonly found in systemic lupus erythematosus."}
{"id": "PMID:221620", "title": "Nervous system complications of herpes zoster: immunofluorescent demonstration of varicella-zoster antigen in CSF cells.", "content": "In nine out of 11 patients with herpes zoster and neurological symptoms varicella-zoster antigen was demonstrated in CSF cells by indirect immunofluorescent staining. Cerebrospinal fluid cytology was in most cases highly suggestive of viral infection. This study demonstrates the value of both immunofluorescent staining on CSF cells and CSF cytology, as corroboration of an otherwise exclusively serologically based virological diagnosis.", "contents": "Nervous system complications of herpes zoster: immunofluorescent demonstration of varicella-zoster antigen in CSF cells. In nine out of 11 patients with herpes zoster and neurological symptoms varicella-zoster antigen was demonstrated in CSF cells by indirect immunofluorescent staining. Cerebrospinal fluid cytology was in most cases highly suggestive of viral infection. This study demonstrates the value of both immunofluorescent staining on CSF cells and CSF cytology, as corroboration of an otherwise exclusively serologically based virological diagnosis."}
{"id": "PMID:221621", "title": "Intracranial pressure in the normal monkey while awake and asleep.", "content": "Intracranial pressure (ICP) was recorded continuously by telemetry in seven normal monkeys trained to eat, sleep, and live in a primate chair. Electroencephalography, electromyography, and blood pressure were also measured by conventional means. During wakefulness and all stages of sleep except desynchronized sleep, the ICP record showed small short-term variations in pressure. However, during desynchronized sleep, the mean ICP rose on the average to 170 +/- 6 mm H2O above the ICP levels in the other states of sleep, and the pulsation pressure variation increased by a factor of three. The episodes occurred 10 +/- 2 times during the night and lasted for 6.8 +/- 1.4 minutes, during which the average systemic blood pressure decreased by 19 +/- 1.6 mm Hg. These ICP waves occurring during desynchronized sleep resemble the plateau waves described by Lundberg, but are of smaller magnitude and they appear to be a normal characteristic of sleep in the macaque monkey. Bilateral sympathectomy of the superior cervical ganglia in four of the monkeys did not alter significantly the duration, amplitude, or frequency of occurrence of the ICP waves during desynchronized sleep.", "contents": "Intracranial pressure in the normal monkey while awake and asleep. Intracranial pressure (ICP) was recorded continuously by telemetry in seven normal monkeys trained to eat, sleep, and live in a primate chair. Electroencephalography, electromyography, and blood pressure were also measured by conventional means. During wakefulness and all stages of sleep except desynchronized sleep, the ICP record showed small short-term variations in pressure. However, during desynchronized sleep, the mean ICP rose on the average to 170 +/- 6 mm H2O above the ICP levels in the other states of sleep, and the pulsation pressure variation increased by a factor of three. The episodes occurred 10 +/- 2 times during the night and lasted for 6.8 +/- 1.4 minutes, during which the average systemic blood pressure decreased by 19 +/- 1.6 mm Hg. These ICP waves occurring during desynchronized sleep resemble the plateau waves described by Lundberg, but are of smaller magnitude and they appear to be a normal characteristic of sleep in the macaque monkey. Bilateral sympathectomy of the superior cervical ganglia in four of the monkeys did not alter significantly the duration, amplitude, or frequency of occurrence of the ICP waves during desynchronized sleep."}
{"id": "PMID:221622", "title": "Spinal subarchnoid metastatic spread from non-neuraxial primary neoplasms. Case report.", "content": "A rare case of metastasis to the spinal subarachnoid space from a non-neuraxial primary tumor is presented. Dissemination was shown by computerized tomography to be via the cerebrospinal fluid from secondary deposits in the central nervous system and meninges. This route would seem to be the most common mode of spread to the spinal subarachnoid space.", "contents": "Spinal subarchnoid metastatic spread from non-neuraxial primary neoplasms. Case report. A rare case of metastasis to the spinal subarachnoid space from a non-neuraxial primary tumor is presented. Dissemination was shown by computerized tomography to be via the cerebrospinal fluid from secondary deposits in the central nervous system and meninges. This route would seem to be the most common mode of spread to the spinal subarachnoid space."}
{"id": "PMID:221625", "title": "Effect of dietary supplementation of iron and ascorbic acid on lead toxicity in rats.", "content": "In our laboratory, the protective and therapeutic effects of surplus dietary iron and ascorbic acid on cadmium toxicity in rats have been studied and in this experiment, an effect of surplus iron and ascorbic acid on lead toxicity was examined. In young rats ingesting a diet containing 500 ppm of lead, growth retardation and anemia were observed. Suplementation of 400 ppm of iron and 1% of ascorbic acid to the lead containing diet prevented the growth depression and anemia and caused reductions of concentrations of lead in the kidney and tibia. Whereas, addition of 50 ppm of cadmium to the lead containing diet aggravated the growth retardation and anemia, but reduced the concentrations of lead in the kidney and tibia. Dietary supplementation of iron to the lead containing diet prevented the growth depression and anemia and reduced the accumulation of lead in the kidney, however the supplementation of ascorbic acid alone did not show any ameliolative effects. Rats were fed the lead containing diet and then transferred to the basal diet with or without iron and ascorbic acid. Recoveries from the growth retardation and anemia were not observed in rats within a week after the transfer to the non-lead diet with or without iron and ascorbic acid. These results suggest that iron prevents the growth depression and anemia in rats ingesting lead by an inhibition of lead asborption.", "contents": "Effect of dietary supplementation of iron and ascorbic acid on lead toxicity in rats. In our laboratory, the protective and therapeutic effects of surplus dietary iron and ascorbic acid on cadmium toxicity in rats have been studied and in this experiment, an effect of surplus iron and ascorbic acid on lead toxicity was examined. In young rats ingesting a diet containing 500 ppm of lead, growth retardation and anemia were observed. Suplementation of 400 ppm of iron and 1% of ascorbic acid to the lead containing diet prevented the growth depression and anemia and caused reductions of concentrations of lead in the kidney and tibia. Whereas, addition of 50 ppm of cadmium to the lead containing diet aggravated the growth retardation and anemia, but reduced the concentrations of lead in the kidney and tibia. Dietary supplementation of iron to the lead containing diet prevented the growth depression and anemia and reduced the accumulation of lead in the kidney, however the supplementation of ascorbic acid alone did not show any ameliolative effects. Rats were fed the lead containing diet and then transferred to the basal diet with or without iron and ascorbic acid. Recoveries from the growth retardation and anemia were not observed in rats within a week after the transfer to the non-lead diet with or without iron and ascorbic acid. These results suggest that iron prevents the growth depression and anemia in rats ingesting lead by an inhibition of lead asborption."}
{"id": "PMID:221626", "title": "Effects of a protein-free diet on the changes in cyclic AMP and cyclic GMP levels induced by immunization in splenic T and B lymphocytes in the rat.", "content": "The levels of cyclic nucleotides, cAMP and cGMP, were determined in splenic lymphocytes of normally fed (N) and protein deprived (PD) rats before and at different time intervals after a single injection of sheep erythrocytes. Assays were performed with protein binding methods on unseparated as well as on T and B cells fractionated by filtration through nylon wool. The cAMP levels increased in unfractionated cells and in T and B lymphocytes 2 hours following immunization of N rats. Another rise in cAMP levels occurred after 3 days in B lymphocytes, but there was also a simultaneous increase of the cGMP levels in preparations of unfractionated cells and in B lymphocytes. The PD diet suppressed or delayed most of the aforementioned changes. Thus, the immunodepressive effect of such a diet may be ascribed to the inhibition of both the early signal (increase of cAMP levels and of cAMP/cGMP ratio) leading to T and B differentiation and the later signal (increase of cGMP levels) which initiates antibody production.", "contents": "Effects of a protein-free diet on the changes in cyclic AMP and cyclic GMP levels induced by immunization in splenic T and B lymphocytes in the rat. The levels of cyclic nucleotides, cAMP and cGMP, were determined in splenic lymphocytes of normally fed (N) and protein deprived (PD) rats before and at different time intervals after a single injection of sheep erythrocytes. Assays were performed with protein binding methods on unseparated as well as on T and B cells fractionated by filtration through nylon wool. The cAMP levels increased in unfractionated cells and in T and B lymphocytes 2 hours following immunization of N rats. Another rise in cAMP levels occurred after 3 days in B lymphocytes, but there was also a simultaneous increase of the cGMP levels in preparations of unfractionated cells and in B lymphocytes. The PD diet suppressed or delayed most of the aforementioned changes. Thus, the immunodepressive effect of such a diet may be ascribed to the inhibition of both the early signal (increase of cAMP levels and of cAMP/cGMP ratio) leading to T and B differentiation and the later signal (increase of cGMP levels) which initiates antibody production."}
{"id": "PMID:221627", "title": "Malignant fibrous histiocytoma of the maxillary sinus.", "content": "A rare localization of a malignant fibrous histiocytoma is presented. Review of the literature showed that the biological behavior of this group of tumors is obscure. The histomorphologic pattern does not always reflect the malignant character, the tendency for recurrence, and the metastasizing potential of the individual tumor. Radiotherapy is ineffective, so the surgeon must opt for radical excision. Additional clinical reports, long-term follow-up, and electron microscopic studies are needed to establish the biological behavior of this group of tumors.", "contents": "Malignant fibrous histiocytoma of the maxillary sinus. A rare localization of a malignant fibrous histiocytoma is presented. Review of the literature showed that the biological behavior of this group of tumors is obscure. The histomorphologic pattern does not always reflect the malignant character, the tendency for recurrence, and the metastasizing potential of the individual tumor. Radiotherapy is ineffective, so the surgeon must opt for radical excision. Additional clinical reports, long-term follow-up, and electron microscopic studies are needed to establish the biological behavior of this group of tumors."}
{"id": "PMID:221628", "title": "Normal growth despite abnormalities of growth hormone secretion in children treated for acute leukemia.", "content": "We have studied the relationship between abnormalities of the growth hormone-somatomedin axis and growth in  26 children previously treated for acute lymphatic leukemia. Each child had previously received cranial irradiation, was in complete clinical and hematologic remission, and off all drugs. The mean standing height SDS of the 26 children was significantly less than normal. There was no significant difference between the mean standing height SDS, height velocity SDS, somatomedin activities, and degree of bone age retardation between the 17 children who received the higher dose of cranial irradiation (Group 1) and the nine who had the lower dose of cranial irradiation (Group II). Furthermore, there was no significant reduction in mean height velocity SDS, somatomedin activity, or bone age in either group when compared to normal age-matched controls. The peak GH responses to both insulin hypoglycemia and an arginine test were significantly lowered in Groups I and II when compared to a control group of children. We conclude that only a minority of children, who previously received cranial irradiation for ALL were clinically GH deficient and, therefore, likely to benefit from GH therapy despite the finding that the majority of these children had reduced GH responses to pharmacologic stimuli.", "contents": "Normal growth despite abnormalities of growth hormone secretion in children treated for acute leukemia. We have studied the relationship between abnormalities of the growth hormone-somatomedin axis and growth in  26 children previously treated for acute lymphatic leukemia. Each child had previously received cranial irradiation, was in complete clinical and hematologic remission, and off all drugs. The mean standing height SDS of the 26 children was significantly less than normal. There was no significant difference between the mean standing height SDS, height velocity SDS, somatomedin activities, and degree of bone age retardation between the 17 children who received the higher dose of cranial irradiation (Group 1) and the nine who had the lower dose of cranial irradiation (Group II). Furthermore, there was no significant reduction in mean height velocity SDS, somatomedin activity, or bone age in either group when compared to normal age-matched controls. The peak GH responses to both insulin hypoglycemia and an arginine test were significantly lowered in Groups I and II when compared to a control group of children. We conclude that only a minority of children, who previously received cranial irradiation for ALL were clinically GH deficient and, therefore, likely to benefit from GH therapy despite the finding that the majority of these children had reduced GH responses to pharmacologic stimuli."}
{"id": "PMID:221630", "title": "Rickets with alopecia: an inborn error of vitamin D metabolism.", "content": "Rickets with alopecia, an inborn error of vitamin D metabolism, is described in two sisters. The rachitic disorder began during the first year of life and was refractory to 50,000 IU of vitamin D2/day. Surprisingly, both children had marked elevations in serum concentrations of 1,25-(OH)2D. Although the molecular basis for this disorder is not evident to date, intestinal end-organ unresponsiveness to exceedingly high levels of 1,25-(OH)2D was present, in addition to hyporesponsiveness of bone to these high levels of the hormone, since normocalcemia was maintained despite elevated serum levels of PTH. Therapy with oral 1,25-(OH)2D3 failed to reverse the disorder, but oral phosphorus supplements resulted in significant radiographic and clinical improvement.", "contents": "Rickets with alopecia: an inborn error of vitamin D metabolism. Rickets with alopecia, an inborn error of vitamin D metabolism, is described in two sisters. The rachitic disorder began during the first year of life and was refractory to 50,000 IU of vitamin D2/day. Surprisingly, both children had marked elevations in serum concentrations of 1,25-(OH)2D. Although the molecular basis for this disorder is not evident to date, intestinal end-organ unresponsiveness to exceedingly high levels of 1,25-(OH)2D was present, in addition to hyporesponsiveness of bone to these high levels of the hormone, since normocalcemia was maintained despite elevated serum levels of PTH. Therapy with oral 1,25-(OH)2D3 failed to reverse the disorder, but oral phosphorus supplements resulted in significant radiographic and clinical improvement."}
{"id": "PMID:221643", "title": "Evidence for distinct prostaglandin I2 and D2 receptors in human platelets.", "content": "Incubation of human platelet-rich plasma with prostaglandin I2 (PGI2), results in a marked increase in adenosine 3':5'-monophosphate (cAMP) that persists for at least 60 min. The persistent stimulation of cAMP levels by PGI2 can be rapidly reversed by the addition of either prostaglandin E1 or E2 (PGE1, PGE2), but not by prostaglandin D2 (PGD2). Studies of agonist-specific desensitization of cAMP accumulation show that PGE1 or PGE2 can desensitize for subsequent PGE or PGI2 activation, and that subthreshold levels of PGI2 desensitize for subsequent PGE1 stimulation. PGD2 desensitizes for consequent PGD2 activation, but not for PGE1, PGE2 or PGI2, and PGE compounds and PGI2 do not desensitize for subsequent PGD2 activation. Agonist-specific desensitization for PGI2 is not dependent on cAMP accumulation, but appears to be a consequence of receptor occupation. Support of the desensitization experiments was obtained through the use of the prostaglandin antagonist N-0164 [sodium-p-benzyl-4-[-oxo-2-(4-chlorobenzyl)-3-phenyl-propyl]phenyl phosphonate). This compound proved to be a potent antagonist of PGD2 and a weak antagonist of PGI2-stimulated cAMP accumulation. These data indicate that human platelets have distinct pharmacological receptors for both PGI2 and PGD2, and that PGE compounds may actually interact with a PGI2 receptor.", "contents": "Evidence for distinct prostaglandin I2 and D2 receptors in human platelets. Incubation of human platelet-rich plasma with prostaglandin I2 (PGI2), results in a marked increase in adenosine 3':5'-monophosphate (cAMP) that persists for at least 60 min. The persistent stimulation of cAMP levels by PGI2 can be rapidly reversed by the addition of either prostaglandin E1 or E2 (PGE1, PGE2), but not by prostaglandin D2 (PGD2). Studies of agonist-specific desensitization of cAMP accumulation show that PGE1 or PGE2 can desensitize for subsequent PGE or PGI2 activation, and that subthreshold levels of PGI2 desensitize for subsequent PGE1 stimulation. PGD2 desensitizes for consequent PGD2 activation, but not for PGE1, PGE2 or PGI2, and PGE compounds and PGI2 do not desensitize for subsequent PGD2 activation. Agonist-specific desensitization for PGI2 is not dependent on cAMP accumulation, but appears to be a consequence of receptor occupation. Support of the desensitization experiments was obtained through the use of the prostaglandin antagonist N-0164 [sodium-p-benzyl-4-[-oxo-2-(4-chlorobenzyl)-3-phenyl-propyl]phenyl phosphonate). This compound proved to be a potent antagonist of PGD2 and a weak antagonist of PGI2-stimulated cAMP accumulation. These data indicate that human platelets have distinct pharmacological receptors for both PGI2 and PGD2, and that PGE compounds may actually interact with a PGI2 receptor."}
{"id": "PMID:221646", "title": "Psychiatric nursing consultation: the use of an inservice model to assist nurses in the grief process.", "content": "This paper proposes that death is a situation which nurses face on a daily basis. Anxiety, depression, and hostility are defined as feelings common to nurses in working with dying patients. Anxiety and depression were significantly lowered in nurses who attended at least three of the five inservice sessions. Hostility levels did not significantly change. This paper also examines the role of the psychiatric nruse consultant in assisting staff nurses to improve the quality of care provided by examining their own emotional system. The consultant can act as faciltator of the group process so that nurses can continue to function independent of the consultant after the consulting process has ended. The psychiatric nurse consultant can utilize inservice curricula such as the one described above to produce affective change in nurses who work with dying patients, which has the potential to improve the quality of care given to the dying.", "contents": "Psychiatric nursing consultation: the use of an inservice model to assist nurses in the grief process. This paper proposes that death is a situation which nurses face on a daily basis. Anxiety, depression, and hostility are defined as feelings common to nurses in working with dying patients. Anxiety and depression were significantly lowered in nurses who attended at least three of the five inservice sessions. Hostility levels did not significantly change. This paper also examines the role of the psychiatric nruse consultant in assisting staff nurses to improve the quality of care provided by examining their own emotional system. The consultant can act as faciltator of the group process so that nurses can continue to function independent of the consultant after the consulting process has ended. The psychiatric nurse consultant can utilize inservice curricula such as the one described above to produce affective change in nurses who work with dying patients, which has the potential to improve the quality of care given to the dying."}
{"id": "PMID:221651", "title": "A framework for the emergency evaluation of the suicidal patient.", "content": "With increasing frequency, emergency room personnel face the anxiety of assessing suicide potential. The authors have developed and present here a mnemonic (SAD CHILDREN) which should facilitate the evaluation of potential in attempted or threatened suicide patients.", "contents": "A framework for the emergency evaluation of the suicidal patient. With increasing frequency, emergency room personnel face the anxiety of assessing suicide potential. The authors have developed and present here a mnemonic (SAD CHILDREN) which should facilitate the evaluation of potential in attempted or threatened suicide patients."}
{"id": "PMID:221653", "title": "Teaching interpersonal management for effective professional nursing practice.", "content": "The treatment environment is an important component of patient care. In order to provide more effective patient care one would want to be able to manipulate the environment, particularly the emotional environment. This is difficult to do and even more difficult to teach. The authors describe a teaching module in a baccalaureate program in nursing in which didactic sessions and behavioral rehearsal analysis techniques are combined. The goal is to teach interpersonal manipulation for more effective management of professional nursing practice. The results have been promising.", "contents": "Teaching interpersonal management for effective professional nursing practice. The treatment environment is an important component of patient care. In order to provide more effective patient care one would want to be able to manipulate the environment, particularly the emotional environment. This is difficult to do and even more difficult to teach. The authors describe a teaching module in a baccalaureate program in nursing in which didactic sessions and behavioral rehearsal analysis techniques are combined. The goal is to teach interpersonal manipulation for more effective management of professional nursing practice. The results have been promising."}
{"id": "PMID:221654", "title": "Identification of typologies derived from child behaviors in the hospital as predictors of psychological upset.", "content": "This study proposed to measure objectively the behaviors of children in the hospital setting in order to combine the data on the particular aspects of behaviors or symptoms into global measures or typologies of psychological upset. It attempts to offer a good, single measure for predicting behavior of children in psychological upset. Thirty-one subjects in this study, observed in the hospital setting, are clustered together to identify typologies derived from child behaviors in the hospital. These children were divided into three factors which correspond with the three stages of hospitalization: Factor I typified Stage III -- Denial; Factor II typified Stage II -- Despair; and Factor III typified Stage I -- Protest. The study offers direction to objectively and systematically evaluate the effects of hospitalization on children. It also suggests that observational ratings of child behaviors in the hospital may be accurate predictors of the degree of psychological upset a child is experiencing at a certain point in time. It also has particular implications for strategies which hospital staff could employ when they observe particular stages that children manifest.", "contents": "Identification of typologies derived from child behaviors in the hospital as predictors of psychological upset. This study proposed to measure objectively the behaviors of children in the hospital setting in order to combine the data on the particular aspects of behaviors or symptoms into global measures or typologies of psychological upset. It attempts to offer a good, single measure for predicting behavior of children in psychological upset. Thirty-one subjects in this study, observed in the hospital setting, are clustered together to identify typologies derived from child behaviors in the hospital. These children were divided into three factors which correspond with the three stages of hospitalization: Factor I typified Stage III -- Denial; Factor II typified Stage II -- Despair; and Factor III typified Stage I -- Protest. The study offers direction to objectively and systematically evaluate the effects of hospitalization on children. It also suggests that observational ratings of child behaviors in the hospital may be accurate predictors of the degree of psychological upset a child is experiencing at a certain point in time. It also has particular implications for strategies which hospital staff could employ when they observe particular stages that children manifest."}
{"id": "PMID:221655", "title": "Development and evaluation of social skills training for schizophrenic patients in remission.", "content": "Investigated were measures of self-esteem, self-perceived attitudinal dimensions and locus of control to assess the effects of group social skills training for schizophrenic psychiatric inpatients. A pretest, posttest control group design was employed utilizing forty subjects currently in treatment. It was hypothesized that short-term cognitively structured group therapy would realize significant improvement in self-esteem, internal locus of control and assertive attitude change. Significant mean differences between the treatment group's level of self-esteem, perceived assertive behavior and internal locus of control as a result of treatment were realized. Discussion of training methodology, issues and import for clinical applications and research are discussed.", "contents": "Development and evaluation of social skills training for schizophrenic patients in remission. Investigated were measures of self-esteem, self-perceived attitudinal dimensions and locus of control to assess the effects of group social skills training for schizophrenic psychiatric inpatients. A pretest, posttest control group design was employed utilizing forty subjects currently in treatment. It was hypothesized that short-term cognitively structured group therapy would realize significant improvement in self-esteem, internal locus of control and assertive attitude change. Significant mean differences between the treatment group's level of self-esteem, perceived assertive behavior and internal locus of control as a result of treatment were realized. Discussion of training methodology, issues and import for clinical applications and research are discussed."}
{"id": "PMID:221656", "title": "A group self-care approach to stress management.", "content": "A procedure is described for teaching patients the use of relaxation as a coping skill. The procedure, called Stress Management Training, combines Progressive Relaxation and Clinical Meditation into a standardized but flexible seven-session protocol. The technique has been used to treat a variety of stress-related medical and psychological problems. The training consists of three components. The first is giving the patient a cognitive understanding of stress and relaxation. The second, teaching the patient to relax by controlling the muscle tension and sympathetic nervous system activity. The third, teaching the patient to generalize the relaxation skill to real-life stress situations. Patients are also instructed in the relationship between stress, basic health practices, and physical health status.", "contents": "A group self-care approach to stress management. A procedure is described for teaching patients the use of relaxation as a coping skill. The procedure, called Stress Management Training, combines Progressive Relaxation and Clinical Meditation into a standardized but flexible seven-session protocol. The technique has been used to treat a variety of stress-related medical and psychological problems. The training consists of three components. The first is giving the patient a cognitive understanding of stress and relaxation. The second, teaching the patient to relax by controlling the muscle tension and sympathetic nervous system activity. The third, teaching the patient to generalize the relaxation skill to real-life stress situations. Patients are also instructed in the relationship between stress, basic health practices, and physical health status."}
{"id": "PMID:221658", "title": "2'-O-Acyl-6-thioinosine cyclic 3',5'-phosphates as prodrugs of thioinosinic acid.", "content": "A series of 2'-O-acyl derivatives of 6-thioinosine cyclic 3',5'-phosphate (6-HS-cRMP) were prepared and examined for their cytotoxic effects on S49 mouse lymphoma cells which were deficient in hypoxanthine-guanine phosphoribosyltransferase (HGPRTase). Cytotoxicity increased with the lipophilicity of the acyl group to a lowest EC50 of 65 micrometer for the 2'-O-palmityl derivative. Addition of a mutation in the gene for cAMP-dependent protein kinase to the HGPRTase-deficient cell line confers resistance to 2'-O-butyryl-cAMP but not to 2'-O-butyryl-6-HS-cRMP, indicating that the latter does not exert its toxic effect via activation of protein kinase. The time course of cell kill by 2'-O-palmityl-6-HS-cRMP resembled that of 6-mercaptopurine and not that of cyclic AMP in these cells. The data suggest that the intact cyclic nucleotides are penetrating the cells and being converted, by phosphodiesterase action and deacylation, to the first toxic metabolite of 6-mercaptopurine, thioinosinic acid.", "contents": "2'-O-Acyl-6-thioinosine cyclic 3',5'-phosphates as prodrugs of thioinosinic acid. A series of 2'-O-acyl derivatives of 6-thioinosine cyclic 3',5'-phosphate (6-HS-cRMP) were prepared and examined for their cytotoxic effects on S49 mouse lymphoma cells which were deficient in hypoxanthine-guanine phosphoribosyltransferase (HGPRTase). Cytotoxicity increased with the lipophilicity of the acyl group to a lowest EC50 of 65 micrometer for the 2'-O-palmityl derivative. Addition of a mutation in the gene for cAMP-dependent protein kinase to the HGPRTase-deficient cell line confers resistance to 2'-O-butyryl-cAMP but not to 2'-O-butyryl-6-HS-cRMP, indicating that the latter does not exert its toxic effect via activation of protein kinase. The time course of cell kill by 2'-O-palmityl-6-HS-cRMP resembled that of 6-mercaptopurine and not that of cyclic AMP in these cells. The data suggest that the intact cyclic nucleotides are penetrating the cells and being converted, by phosphodiesterase action and deacylation, to the first toxic metabolite of 6-mercaptopurine, thioinosinic acid."}
{"id": "PMID:221659", "title": "Coupled sodium-chloride influx across brush border of flounder intestine.", "content": "Measurements of the unidirectional influxes of Na and Cl from the mucosal solution into the epithelium (Jme) of flounder intestine under short-circuit conditions reveal the presence of a coupled NaCl influx process at the brush border membrane which appears to be essential for the absorption of these ions. JClme and JName were inhibited by replacing Na or Cl, respectively, in the bathing media with non-transported ions which also reduced the short-circuit current (Isc) to near-zero values. Addition of furosemide to the mucosal solution alone inhibited the Isc and reduced JClme and JName under control conditions, but not in the absence of Na or Cl, respectively. The reductions in JClme and JName elicited by ion replacement or furosemide were approximately equal, suggesting that the coupled influx mechanism mediates a one-for-one entry of these ions into the cell from the mucosal solution. Furosemide inhibited Cl absorption by reducing the unidirectional Cl flux from mucosa to serosa, consistent with its inhibition of the influx process. As in other epithelia, coupled NaCl influx is inhibited by cyclic AMP, which accounts for the decrease in Cl absorption elicited by cyclic nucleotides. These results support the notion that transcellular NaCl transport is a neutrla process and that the serosa-negative transepithelial electrical potential difference and preponderance of Cl over Na absorption under short-circuit conditions result from dissimilar permeabilities of the paracellular pathway to Na and Cl.", "contents": "Coupled sodium-chloride influx across brush border of flounder intestine. Measurements of the unidirectional influxes of Na and Cl from the mucosal solution into the epithelium (Jme) of flounder intestine under short-circuit conditions reveal the presence of a coupled NaCl influx process at the brush border membrane which appears to be essential for the absorption of these ions. JClme and JName were inhibited by replacing Na or Cl, respectively, in the bathing media with non-transported ions which also reduced the short-circuit current (Isc) to near-zero values. Addition of furosemide to the mucosal solution alone inhibited the Isc and reduced JClme and JName under control conditions, but not in the absence of Na or Cl, respectively. The reductions in JClme and JName elicited by ion replacement or furosemide were approximately equal, suggesting that the coupled influx mechanism mediates a one-for-one entry of these ions into the cell from the mucosal solution. Furosemide inhibited Cl absorption by reducing the unidirectional Cl flux from mucosa to serosa, consistent with its inhibition of the influx process. As in other epithelia, coupled NaCl influx is inhibited by cyclic AMP, which accounts for the decrease in Cl absorption elicited by cyclic nucleotides. These results support the notion that transcellular NaCl transport is a neutrla process and that the serosa-negative transepithelial electrical potential difference and preponderance of Cl over Na absorption under short-circuit conditions result from dissimilar permeabilities of the paracellular pathway to Na and Cl."}
{"id": "PMID:221663", "title": "Colorectal carcinoma in young persons: experience at Howard University Hospital, 1955--1977.", "content": "Case records of all patients 30 years of age and under with a proven pathological diagnosis of colorectal cancer at Howard University Hospital between January 1955 and December 1977 were reviewed. Over this 23-year period, 14 cases were documented. All patients were black. This study reaffirms the poor prognosis which accompanies colorectal carcinoma in the young, particularly in those patients with mucinous carcinoma.", "contents": "Colorectal carcinoma in young persons: experience at Howard University Hospital, 1955--1977. Case records of all patients 30 years of age and under with a proven pathological diagnosis of colorectal cancer at Howard University Hospital between January 1955 and December 1977 were reviewed. Over this 23-year period, 14 cases were documented. All patients were black. This study reaffirms the poor prognosis which accompanies colorectal carcinoma in the young, particularly in those patients with mucinous carcinoma."}
{"id": "PMID:221665", "title": "Isolation and characterization of a mouse cell line containing a defective Moloney murine leukemia virus genome.", "content": "A culture of mouse cells containing a 1,000-nucleotide deletion mutant of Moloney murine leukemia virus has been isolated. The deletion did not affect the size or function of the 21S mRNA that encodes the env gene products. Both the deleted RNA and the 21S mRNA were recovered in polyribosomes. Cells containing the deleted virus made no detectable Pr180gag-pol. Pr65gag synthesis with also absent, but a 45,000-molecular-weight gag gene product was found that might be encoded by the deleted genome. Biosynthesis of Pr80env proceeded normally in these cells; the intracellular precursor was cleaved and migrated to the cell surface as gp70. The cells could not be superinfected by homologous Moloney murine leukemia virus presumably because of surface restriction due to the gp70. Although the cells express the Moloney murine leukemia virus gp70 on their surface, they will not make pseudotypes after infection with vesicular stomatitis virus implying that Pr65gag may play a critical role in pseudotype formation. Induction of endogenous virus expression in the cells carrying the deletion mutant generated an N-tropic murine leukemia virus that can fuse XC cells. This may represent a recombinant between the deletion mutant and an endogenous virus.", "contents": "Isolation and characterization of a mouse cell line containing a defective Moloney murine leukemia virus genome. A culture of mouse cells containing a 1,000-nucleotide deletion mutant of Moloney murine leukemia virus has been isolated. The deletion did not affect the size or function of the 21S mRNA that encodes the env gene products. Both the deleted RNA and the 21S mRNA were recovered in polyribosomes. Cells containing the deleted virus made no detectable Pr180gag-pol. Pr65gag synthesis with also absent, but a 45,000-molecular-weight gag gene product was found that might be encoded by the deleted genome. Biosynthesis of Pr80env proceeded normally in these cells; the intracellular precursor was cleaved and migrated to the cell surface as gp70. The cells could not be superinfected by homologous Moloney murine leukemia virus presumably because of surface restriction due to the gp70. Although the cells express the Moloney murine leukemia virus gp70 on their surface, they will not make pseudotypes after infection with vesicular stomatitis virus implying that Pr65gag may play a critical role in pseudotype formation. Induction of endogenous virus expression in the cells carrying the deletion mutant generated an N-tropic murine leukemia virus that can fuse XC cells. This may represent a recombinant between the deletion mutant and an endogenous virus."}
{"id": "PMID:221666", "title": "Structure and origin of defective genomes contained in serially passaged herpes simplex virus type 1 (Justin).", "content": "Restriction enzyme and hybridization analyses have revealed that high-density DNA prepared from passage 15 of serially passaged herpes simplex virus type 1 (Justin) contains three major classes of modified viral DNA molecules, each composed of distinct but closely related types of repeate units. The DNA sequences within the three types of repeat units are colinear with the DNA sequences located at the right end (between coordinates 0.94 and 1.0) of the parental herpes simplex virus type 1 genome. Thus, the three types of repeat units each contain the entire repeat sequence (ac) (which brackets the unique sequences of the small [S] component of herpes simplex virus type 1 DNA) and differ only with respect to the amount of unique S sequences which they contain. The three classes of high-density DNA molecules were found to be stably propagated between passages 6 and 15 of this series.", "contents": "Structure and origin of defective genomes contained in serially passaged herpes simplex virus type 1 (Justin). Restriction enzyme and hybridization analyses have revealed that high-density DNA prepared from passage 15 of serially passaged herpes simplex virus type 1 (Justin) contains three major classes of modified viral DNA molecules, each composed of distinct but closely related types of repeate units. The DNA sequences within the three types of repeat units are colinear with the DNA sequences located at the right end (between coordinates 0.94 and 1.0) of the parental herpes simplex virus type 1 genome. Thus, the three types of repeat units each contain the entire repeat sequence (ac) (which brackets the unique sequences of the small [S] component of herpes simplex virus type 1 DNA) and differ only with respect to the amount of unique S sequences which they contain. The three classes of high-density DNA molecules were found to be stably propagated between passages 6 and 15 of this series."}
{"id": "PMID:221667", "title": "Unstable resistance of G mouse fibroblasts to ecotropic murine leukemia virus infection.", "content": "G mouse cells were resistant to N- and NB-tropic Friend leukemia viruses and to B-tropic WN 1802B. Though the cells were resistant to focus formation by the Moloney isolate of murine sarcoma virus, they were relatively sensitive to helper component murine leukemia virus. To amphotropic murine leukemia virus and to focus formation by amphotropic murine sarcoma virus, G mouse cells were fully permissive. When the cell lines were established starting from the individual embryos, most cell lines were not resistant to the murine leukemia viruses. Only one resistant line was established. Cloning of this cell line indicated that the resistant cells constantly segregated sensitive cells during the culture; i.e., the G mouse cell cultures were probably always mixtures of sensitive and resistant cells. Among the sensitive cell clones, some were devoid of Fv-1 restriction. Such dually permissive cells, and also feral mouse-derived SC-1 cells, retained glucose-6-phosphate dehydrogenase-1 and apparently normal number 4 chromosomes. The loss of Fv-1 restriction in these mouse cells was not brought about by any gross structural changes in the vicinity of Fv-1 on number 4 chromosomes.", "contents": "Unstable resistance of G mouse fibroblasts to ecotropic murine leukemia virus infection. G mouse cells were resistant to N- and NB-tropic Friend leukemia viruses and to B-tropic WN 1802B. Though the cells were resistant to focus formation by the Moloney isolate of murine sarcoma virus, they were relatively sensitive to helper component murine leukemia virus. To amphotropic murine leukemia virus and to focus formation by amphotropic murine sarcoma virus, G mouse cells were fully permissive. When the cell lines were established starting from the individual embryos, most cell lines were not resistant to the murine leukemia viruses. Only one resistant line was established. Cloning of this cell line indicated that the resistant cells constantly segregated sensitive cells during the culture; i.e., the G mouse cell cultures were probably always mixtures of sensitive and resistant cells. Among the sensitive cell clones, some were devoid of Fv-1 restriction. Such dually permissive cells, and also feral mouse-derived SC-1 cells, retained glucose-6-phosphate dehydrogenase-1 and apparently normal number 4 chromosomes. The loss of Fv-1 restriction in these mouse cells was not brought about by any gross structural changes in the vicinity of Fv-1 on number 4 chromosomes."}
{"id": "PMID:221668", "title": "Cell-free synthesis of mouse mammary tumor virus Pr77 from virion and intracellular mRNA.", "content": "Mouse mammary tumor virus (MuMTV) was purified from two cell lines (GR and Mm5MT/c1), and the genomic RNA was isolated and translated in vitro in cell-free systems derived from mouse L cells and rabbit reticulocytes. The major translation product in both systems was a protein with the molecular weight 77,000. Several other products were also detected, among them a 110,000-dalton and in minor amounts a 160,000-dalton protein. All three polypeptides were specifically immunoprecipitated by antiserum raised against the major core protein of MuMTV (p27), but they were not precipitated by antiserum against the virion glycoprotein gp52. Analysis of the in vitro products by tryptic peptide mapping established their relationship to the virion non-glycosylated structural proteins. The 77,000-dalton polypeptide was found to be similar, if not identical, to an analogous precursor isolated from MuMTV-producing cells. Peptide mapping of the 110,000-dalton protein shows that it contains all of the methionine-labeled peptides found in the 77,000-dalton protein plus some additional peptides. We conclude that the products synthesized in vitro from the genomic MuMTV RNA are related to the non-glycosylated virion structural proteins. Polyadenylic acid-containing RNA from MuMTV-producing cells also directed the synthesis of the 77,000-dalton polypeptide in the L-cell system. If this RNA preparation was first fractionated by sucrose gradient centrifugation the 77,000-dalton protein appeared to be synthesized from mRNA with a sedimentation coefficient between 25 and 35S.", "contents": "Cell-free synthesis of mouse mammary tumor virus Pr77 from virion and intracellular mRNA. Mouse mammary tumor virus (MuMTV) was purified from two cell lines (GR and Mm5MT/c1), and the genomic RNA was isolated and translated in vitro in cell-free systems derived from mouse L cells and rabbit reticulocytes. The major translation product in both systems was a protein with the molecular weight 77,000. Several other products were also detected, among them a 110,000-dalton and in minor amounts a 160,000-dalton protein. All three polypeptides were specifically immunoprecipitated by antiserum raised against the major core protein of MuMTV (p27), but they were not precipitated by antiserum against the virion glycoprotein gp52. Analysis of the in vitro products by tryptic peptide mapping established their relationship to the virion non-glycosylated structural proteins. The 77,000-dalton polypeptide was found to be similar, if not identical, to an analogous precursor isolated from MuMTV-producing cells. Peptide mapping of the 110,000-dalton protein shows that it contains all of the methionine-labeled peptides found in the 77,000-dalton protein plus some additional peptides. We conclude that the products synthesized in vitro from the genomic MuMTV RNA are related to the non-glycosylated virion structural proteins. Polyadenylic acid-containing RNA from MuMTV-producing cells also directed the synthesis of the 77,000-dalton polypeptide in the L-cell system. If this RNA preparation was first fractionated by sucrose gradient centrifugation the 77,000-dalton protein appeared to be synthesized from mRNA with a sedimentation coefficient between 25 and 35S."}
{"id": "PMID:221669", "title": "Membrane proteins specified by herpes simplex viruses. III. Role of glycoprotein VP7(B2) in virion infectivity.", "content": "Experiments done with a temperature\"sensitive mutant of herpes simplex virus type 1 (HSV-1) have revealed that one of the virisn glycoproteins, designated VP7(B2), is apparently not required for the production of enveloped virus particles, whereas it does play a critical role in virion infectivity. The mutant, designated HSV-1[HFEM]tsB5, fails to accumulate VP7(B2) at nonpermissive temperature and produces virions that lack detectable quantities of this glycoprotein and that have very low specific infectivity. The poor infectivity of the virions is most readily explained by failure of penetration into the host cell rather than by failure of adsorption to cells because it was shown that the VP7(B2)-deficient virions can bind to cells and that polyethylene glycol, an agent known to promote membrane fusion, can significantly enhance infectivity of the adsorbed virions.", "contents": "Membrane proteins specified by herpes simplex viruses. III. Role of glycoprotein VP7(B2) in virion infectivity. Experiments done with a temperature\"sensitive mutant of herpes simplex virus type 1 (HSV-1) have revealed that one of the virisn glycoproteins, designated VP7(B2), is apparently not required for the production of enveloped virus particles, whereas it does play a critical role in virion infectivity. The mutant, designated HSV-1[HFEM]tsB5, fails to accumulate VP7(B2) at nonpermissive temperature and produces virions that lack detectable quantities of this glycoprotein and that have very low specific infectivity. The poor infectivity of the virions is most readily explained by failure of penetration into the host cell rather than by failure of adsorption to cells because it was shown that the VP7(B2)-deficient virions can bind to cells and that polyethylene glycol, an agent known to promote membrane fusion, can significantly enhance infectivity of the adsorbed virions."}
{"id": "PMID:221670", "title": "Membrane proteins specified by herpes simplex viruses. IV. Conformation of the virion glycoprotein designated VP7(B2).", "content": "The herpes simplex virus glycoprotein designated VP7(B2) is extracted from virions by nonionic detergent in the form of an oligomer, whereas the other detergent-soluble envelope proteins appear to be extracted as monomers. The subunits of the VP7(B2) oligomer cannot be dissociated by 2-mercaptoethanol and are also resistant to dissociation by a mixture of sodium dodecyl sulfate and 2-mercaptoethanol, except at elevated temperature. The oligomeric form of solubilized VP7(B2) appears to be predominantly dimeric, based on the sedimentation rats in sucrose gradients and the electrophoretic mobilities in sodium dodecyl sulfate-containing acrylamide gels of the undissociated and heat-dissociated forms of VP7(B2).", "contents": "Membrane proteins specified by herpes simplex viruses. IV. Conformation of the virion glycoprotein designated VP7(B2). The herpes simplex virus glycoprotein designated VP7(B2) is extracted from virions by nonionic detergent in the form of an oligomer, whereas the other detergent-soluble envelope proteins appear to be extracted as monomers. The subunits of the VP7(B2) oligomer cannot be dissociated by 2-mercaptoethanol and are also resistant to dissociation by a mixture of sodium dodecyl sulfate and 2-mercaptoethanol, except at elevated temperature. The oligomeric form of solubilized VP7(B2) appears to be predominantly dimeric, based on the sedimentation rats in sucrose gradients and the electrophoretic mobilities in sodium dodecyl sulfate-containing acrylamide gels of the undissociated and heat-dissociated forms of VP7(B2)."}
{"id": "PMID:221671", "title": "Virus-like 30S RNA in mouse cells.", "content": "Uninfected JLS-V9 mouse cells are known to express high levels of viral sequences that hybridize to complementary DNA made by the BrdU-induced virus of JLS-V9 cells. The genome in the BrdU-induced virus has been found to consist mainly of an RNA species that migrates as 30S RNA material during electrophoresis through agarose gels. This virus-like 30S RNA, designated VL30 RNA, apparently represents a new class of endogenous defective retroviruses that are not generally evident because of their defectiveness and lack of biological function. Fingerprint analysis and hybridization studies show that VL30 RNA does not have homology with the standard nondefective murine leukemia viruses. Upon superinfection with a nondefective murine leukemia virus, or upon induction of endogenous virus with BrdU, VL30 RNA is rescued into virions by phenotypic mixing. When VL30 RNA is rescued by BrdU induction, the VL30 RNA is mainly organized as a 50S complex, but when VL30 is rescued by superinfection, VL30 is also found in 70S RNA. Rescued VL30 RNA sequences can be reverse transcribed by the virion-associated DNA polymerase in an endogenous reaction. Many mouse cells express the sequences, whereas heterologous cells such as rat or rabbit cells do not contain them. By using hybridization of a complementary DNA probe to cellular RNA immobilized on paper, no subgenomic RNA related to the VL30 RNA could be found in cells expressing the VL30 sequences. From 20 to 50 copies of these sequences were found to be contained in the mouse genome. VL30 RNA is probably present in most stocks of leukemia and sarcoma viruses made in mouse cells.", "contents": "Virus-like 30S RNA in mouse cells. Uninfected JLS-V9 mouse cells are known to express high levels of viral sequences that hybridize to complementary DNA made by the BrdU-induced virus of JLS-V9 cells. The genome in the BrdU-induced virus has been found to consist mainly of an RNA species that migrates as 30S RNA material during electrophoresis through agarose gels. This virus-like 30S RNA, designated VL30 RNA, apparently represents a new class of endogenous defective retroviruses that are not generally evident because of their defectiveness and lack of biological function. Fingerprint analysis and hybridization studies show that VL30 RNA does not have homology with the standard nondefective murine leukemia viruses. Upon superinfection with a nondefective murine leukemia virus, or upon induction of endogenous virus with BrdU, VL30 RNA is rescued into virions by phenotypic mixing. When VL30 RNA is rescued by BrdU induction, the VL30 RNA is mainly organized as a 50S complex, but when VL30 is rescued by superinfection, VL30 is also found in 70S RNA. Rescued VL30 RNA sequences can be reverse transcribed by the virion-associated DNA polymerase in an endogenous reaction. Many mouse cells express the sequences, whereas heterologous cells such as rat or rabbit cells do not contain them. By using hybridization of a complementary DNA probe to cellular RNA immobilized on paper, no subgenomic RNA related to the VL30 RNA could be found in cells expressing the VL30 sequences. From 20 to 50 copies of these sequences were found to be contained in the mouse genome. VL30 RNA is probably present in most stocks of leukemia and sarcoma viruses made in mouse cells."}
{"id": "PMID:221672", "title": "Persistent BK papovavirus infection of transformed human fetal brain cells. I. Episomal viral DNA in cloned lines deficient in T-antigen expression.", "content": "After infection of permissive human fetal brain cells by BK human papovavirus (BKV), the vast majority of the cells were killed by the virus, but rare survivors were recovered after frequent medium changes. These surviving cells grew and formed visible colonies after 5 to 6 weeks and were thereafter established as permanent cell lines. These cells, designated as BK-HFB cells, were persistently infected and shed BKV. Morphologically, they were small polygonal cells and had transformed growth properties. Their plating efficiency on solid substrates or in semisolid medium was high, and they were tumorigenic in athymic nude mice. Cloning experiments in medium containing BKV antiserum revealed that BKV did not persist in the cultures in a simple carrier state. All cloned cell lines were initially T-antigen negative and virus-free. However, every clone began to release BKV and again became persistently infected within 3 weeks after removal of BKV antiserum. After rigorous antibody treatment, four of seven clones still released virus spontaneously upon removal of antiserum; three clones have remained virus-free and are apparently cured. Although these cloned cell lines are T- and V-antigen negative when grown in antiserum-containing medium, they retain \"free\" or episomal BKV genomes; integrated viral DNA was not detected in any of the clones. These free genomes are indistinguishable from prototype BKV DNA and are found in much larger amounts in virus-shedding cell lines.", "contents": "Persistent BK papovavirus infection of transformed human fetal brain cells. I. Episomal viral DNA in cloned lines deficient in T-antigen expression. After infection of permissive human fetal brain cells by BK human papovavirus (BKV), the vast majority of the cells were killed by the virus, but rare survivors were recovered after frequent medium changes. These surviving cells grew and formed visible colonies after 5 to 6 weeks and were thereafter established as permanent cell lines. These cells, designated as BK-HFB cells, were persistently infected and shed BKV. Morphologically, they were small polygonal cells and had transformed growth properties. Their plating efficiency on solid substrates or in semisolid medium was high, and they were tumorigenic in athymic nude mice. Cloning experiments in medium containing BKV antiserum revealed that BKV did not persist in the cultures in a simple carrier state. All cloned cell lines were initially T-antigen negative and virus-free. However, every clone began to release BKV and again became persistently infected within 3 weeks after removal of BKV antiserum. After rigorous antibody treatment, four of seven clones still released virus spontaneously upon removal of antiserum; three clones have remained virus-free and are apparently cured. Although these cloned cell lines are T- and V-antigen negative when grown in antiserum-containing medium, they retain \"free\" or episomal BKV genomes; integrated viral DNA was not detected in any of the clones. These free genomes are indistinguishable from prototype BKV DNA and are found in much larger amounts in virus-shedding cell lines."}
{"id": "PMID:221673", "title": "Detection of the viral sarcoma gene product in cells infected with various strains of avian sarcoma virus and of a related protein in uninfected chicken cells.", "content": "Genetic analyses have defined a single gene (src) as that portion of the avian sarcoma virus (ASV) genome which encodes the protein directly responsible for ASV-induced neoplastic transformation. We have recently identified the polypeptide product of the src gene of the Schmidt-Ruppin (SR) strain of ASV, a 60,000-dalton phosphoprotein designated pp60(src), and have further determined that pp60(src) acts as a protein kinase. Essential to the identification and characterization of the pp60(src) protein of SR-ASV was the use of serum (TBR serum) from rabbits bearing SR-ASV-induced tumors. TBR serum was, however, strain specific, recognizing pp60(src) from SR-ASV-transformed cells only. We report here that sera from marmosets bearing tumors induced by the Bryan or SR strains of ASV (TBM sera) contain antibody which precipitates the transforming gene product from cells transformed by the SR, Bryan, Prague, or Bratislava strains of ASV. In contrast, rabbits bearing tumors induced by either the Bratislava or Bryan strains of ASV, or hamsters with SR-ASV-induced tumors did not produce antibody to pp60(src) from any strain of ASV. The 60,000-dalton polypeptides immunoprecipitated with TBM serum from cells transformed by each of the above virus strains are phosphoproteins. One-dimensional peptide mapping by limited proteolysis revealed that the pp60(src) proteins are structurally very similar, but not identical. Furthermore, all of the viral pp60(src) proteins have an associated phosphotransferase activity. In addition to detecting the viral src proteins, TBM serum was able to immunoprecipitate an antigenically related protein from normal uninfected avian cells.", "contents": "Detection of the viral sarcoma gene product in cells infected with various strains of avian sarcoma virus and of a related protein in uninfected chicken cells. Genetic analyses have defined a single gene (src) as that portion of the avian sarcoma virus (ASV) genome which encodes the protein directly responsible for ASV-induced neoplastic transformation. We have recently identified the polypeptide product of the src gene of the Schmidt-Ruppin (SR) strain of ASV, a 60,000-dalton phosphoprotein designated pp60(src), and have further determined that pp60(src) acts as a protein kinase. Essential to the identification and characterization of the pp60(src) protein of SR-ASV was the use of serum (TBR serum) from rabbits bearing SR-ASV-induced tumors. TBR serum was, however, strain specific, recognizing pp60(src) from SR-ASV-transformed cells only. We report here that sera from marmosets bearing tumors induced by the Bryan or SR strains of ASV (TBM sera) contain antibody which precipitates the transforming gene product from cells transformed by the SR, Bryan, Prague, or Bratislava strains of ASV. In contrast, rabbits bearing tumors induced by either the Bratislava or Bryan strains of ASV, or hamsters with SR-ASV-induced tumors did not produce antibody to pp60(src) from any strain of ASV. The 60,000-dalton polypeptides immunoprecipitated with TBM serum from cells transformed by each of the above virus strains are phosphoproteins. One-dimensional peptide mapping by limited proteolysis revealed that the pp60(src) proteins are structurally very similar, but not identical. Furthermore, all of the viral pp60(src) proteins have an associated phosphotransferase activity. In addition to detecting the viral src proteins, TBM serum was able to immunoprecipitate an antigenically related protein from normal uninfected avian cells."}
{"id": "PMID:221674", "title": "Cell-free translation of simian virus 40 16S and 19S L-strand-specific mRNA classes to simian virus 40 major VP-1 and minor VP-2 and VP-3 capsid proteins.", "content": "Simian virus 40 capsid proteins VP-1, VP-2, and VP-3 have been synthesized in wheat germ and reticulocyte cell-free systems in response to either poly(A)-containing mRNA from the cytoplasm of infected cells or viral RNA purified by hybridization to simian virus 40 DNA linked to Sepharose. All three viral polypeptides synthesized in vitro are specifically immunoprecipitated with anti-simian virus 40 capsid serum. VP-2 and VP-3 are related by tryptic peptide mapping to each other but not to VP-1. The most abundant class of L-strand-specific viral mRNA, the 16S species, codes for the major capsid protein. The relatively minor 19S class directs the cell-free synthesis of VP-1, VP-2, and VP-3. Whether the 19S RNA represents more than one distinct species of mRNA is not yet clear. VP-1 mRNA can be isolated from the cytoplasm, detergent-washed nuclei, and the nuclear wash fraction. The mRNA from the nuclear wash fraction is enriched for VP-2 mRNA when compared to other viral or cellular polypeptides.", "contents": "Cell-free translation of simian virus 40 16S and 19S L-strand-specific mRNA classes to simian virus 40 major VP-1 and minor VP-2 and VP-3 capsid proteins. Simian virus 40 capsid proteins VP-1, VP-2, and VP-3 have been synthesized in wheat germ and reticulocyte cell-free systems in response to either poly(A)-containing mRNA from the cytoplasm of infected cells or viral RNA purified by hybridization to simian virus 40 DNA linked to Sepharose. All three viral polypeptides synthesized in vitro are specifically immunoprecipitated with anti-simian virus 40 capsid serum. VP-2 and VP-3 are related by tryptic peptide mapping to each other but not to VP-1. The most abundant class of L-strand-specific viral mRNA, the 16S species, codes for the major capsid protein. The relatively minor 19S class directs the cell-free synthesis of VP-1, VP-2, and VP-3. Whether the 19S RNA represents more than one distinct species of mRNA is not yet clear. VP-1 mRNA can be isolated from the cytoplasm, detergent-washed nuclei, and the nuclear wash fraction. The mRNA from the nuclear wash fraction is enriched for VP-2 mRNA when compared to other viral or cellular polypeptides."}
{"id": "PMID:221675", "title": "In vitro selection of high-infectious, leukemogenic virus from low-infectious, non-leukemogenic type C virus from a malignant ST/a mouse cell line.", "content": "Low-infectious, nontransforming type C virus was isolated from an in vitro spontaneously transformed ST/a mouse cell line, ST-L1. The virus released by ST-L1 cells was NB-tropic and XC(-). It gave rise to very small peroxidase antibody plaques (PAP) in cultures which initially were nonproducing. Sodium dodecyl sulfate (SDS)-polyacrylamide gels of the structural proteins of the ST-L1 virus showed an envelope glycoprotein with an apparent mass of 65 kilodaltons (kdal). The mouse cells SC-1, BALB/3T3, and NIH/3T3 could be productively infected with cell-free supernatants from the ST-L1 cell line; however, virus was detected in supernatant fluids only after two to four subcultures of the infected cells. The virus thus produced was XC(+) and a large plaque former. The virus released from infected SC-1 cells was N-tropic, whereas the viruses from infected NIH/3T3 and BALB/3T3 cells were NB-tropic. The structural proteins of the N- and NB-tropic viruses could be distinguished on SDS polyacrylamide gels, the major dissimilarity being a difference in the mobility of the p30. All these viruses had an envelope glycoprotein with an apparent mass of 70 kdal. The infectivity of the viruses, measured as PAP per nanogram of p30, was 30- to 60-fold lower for the virus released from the ST-L1 cell line than that of the viruses after passage in SC-1, NIH/3T3, and BALB/3T3 cells. None of the viruses could infect rabbit or mink cells. Inoculation of the viruses into newborn mice showed that the ST-L1 virus was non-leukemogenic, whereas the NB-tropic virus selected from this after passage in BALB/3T3 or NIH/3T3 cells was highly leukemogenic. Viruses isolated from leukemic animals were indistinguishable with respect to host range and protein mobilities in SDS gels from the ones with which the mice were inoculated. Although the SC-1-selected virus was highly infectious in vitro, it was only weakly, if at all, leukemogenic.", "contents": "In vitro selection of high-infectious, leukemogenic virus from low-infectious, non-leukemogenic type C virus from a malignant ST/a mouse cell line. Low-infectious, nontransforming type C virus was isolated from an in vitro spontaneously transformed ST/a mouse cell line, ST-L1. The virus released by ST-L1 cells was NB-tropic and XC(-). It gave rise to very small peroxidase antibody plaques (PAP) in cultures which initially were nonproducing. Sodium dodecyl sulfate (SDS)-polyacrylamide gels of the structural proteins of the ST-L1 virus showed an envelope glycoprotein with an apparent mass of 65 kilodaltons (kdal). The mouse cells SC-1, BALB/3T3, and NIH/3T3 could be productively infected with cell-free supernatants from the ST-L1 cell line; however, virus was detected in supernatant fluids only after two to four subcultures of the infected cells. The virus thus produced was XC(+) and a large plaque former. The virus released from infected SC-1 cells was N-tropic, whereas the viruses from infected NIH/3T3 and BALB/3T3 cells were NB-tropic. The structural proteins of the N- and NB-tropic viruses could be distinguished on SDS polyacrylamide gels, the major dissimilarity being a difference in the mobility of the p30. All these viruses had an envelope glycoprotein with an apparent mass of 70 kdal. The infectivity of the viruses, measured as PAP per nanogram of p30, was 30- to 60-fold lower for the virus released from the ST-L1 cell line than that of the viruses after passage in SC-1, NIH/3T3, and BALB/3T3 cells. None of the viruses could infect rabbit or mink cells. Inoculation of the viruses into newborn mice showed that the ST-L1 virus was non-leukemogenic, whereas the NB-tropic virus selected from this after passage in BALB/3T3 or NIH/3T3 cells was highly leukemogenic. Viruses isolated from leukemic animals were indistinguishable with respect to host range and protein mobilities in SDS gels from the ones with which the mice were inoculated. Although the SC-1-selected virus was highly infectious in vitro, it was only weakly, if at all, leukemogenic."}
{"id": "PMID:221676", "title": "Infectivity of proviral DNA from avian sarcoma virus-transformed mammalian cells.", "content": "The number of Rous viral genomes in the cellular DNA from two subclones (RS2/3, RS2/6) derived from the same clone of hamster BHK-21 cells transformed by Rous sarcoma virus was determined by hybridization with viral complementary DNA made in vitro, and the capacity of the cellular DNA to infect (transfect) chicken embryo fibroblasts was compared before and after shearing this DNA to about the size of the provirus (6 x 10(6) to 7 x 10(6) daltons). The two subclones differed widely both in their capacity to give rise to virus (inducibility) after fusion with chicken embryo fibroblasts and in level of expression of viral proteins. It was shown that cells of both subclones contain a single copy of Rous DNA and yield infectious DNA. However, whereas transfection of chicken embryo fibroblasts was successful with both unsheared (>/=18 x 10(6) daltons) and sheared DNA from the most inducible subclone (RS2/3 subclone), which also expresses viral proteins to an appreciable amount, transfection with DNA from the least inducible subclone (RS2/6 subclone), in which viral proteins are not expressed, succeeded only with sheared DNA. It was then about as successful as with sheared or unsheared RS2/3 DNA. The lack of infectivity of unsheared RS2/6 DNA may be explained by the hypothesis proposed by Cooper and Temin (G. M. Cooper and H. T. Temin, J. Virol. 17:422-430, 1976) to explain the lack of infectivity of DNA from certain chicken cells producing spontaneously low amounts of RAV-0 and resistant to exogenous RAV-0 infection, that is, that the viral genome (proviral DNA) is linked to a cis-acting control element which blocks its expression. This linkage might originate, in RS2/6 cells, from translocation of cellular DNA containing the single proviral copy.", "contents": "Infectivity of proviral DNA from avian sarcoma virus-transformed mammalian cells. The number of Rous viral genomes in the cellular DNA from two subclones (RS2/3, RS2/6) derived from the same clone of hamster BHK-21 cells transformed by Rous sarcoma virus was determined by hybridization with viral complementary DNA made in vitro, and the capacity of the cellular DNA to infect (transfect) chicken embryo fibroblasts was compared before and after shearing this DNA to about the size of the provirus (6 x 10(6) to 7 x 10(6) daltons). The two subclones differed widely both in their capacity to give rise to virus (inducibility) after fusion with chicken embryo fibroblasts and in level of expression of viral proteins. It was shown that cells of both subclones contain a single copy of Rous DNA and yield infectious DNA. However, whereas transfection of chicken embryo fibroblasts was successful with both unsheared (>/=18 x 10(6) daltons) and sheared DNA from the most inducible subclone (RS2/3 subclone), which also expresses viral proteins to an appreciable amount, transfection with DNA from the least inducible subclone (RS2/6 subclone), in which viral proteins are not expressed, succeeded only with sheared DNA. It was then about as successful as with sheared or unsheared RS2/3 DNA. The lack of infectivity of unsheared RS2/6 DNA may be explained by the hypothesis proposed by Cooper and Temin (G. M. Cooper and H. T. Temin, J. Virol. 17:422-430, 1976) to explain the lack of infectivity of DNA from certain chicken cells producing spontaneously low amounts of RAV-0 and resistant to exogenous RAV-0 infection, that is, that the viral genome (proviral DNA) is linked to a cis-acting control element which blocks its expression. This linkage might originate, in RS2/6 cells, from translocation of cellular DNA containing the single proviral copy."}
{"id": "PMID:221677", "title": "Restriction endonuclease cleavage map of the DNA of JC virus.", "content": "A physical map of the sites cleaved by the following restriction endonucleases was derived for the DNA of JC virus, a human polyomavirus: EcoRI, HpaI, and PstI (one site each); HindII (four sites); and HindIII (three sites). By agarose gel electrophoresis of fragmented DNA, the size of full-length DNA of JC virus was estimated to be 5,125 +/- 105 base pairs (98 +/- 2% of the length of simian virus 40 DNA).", "contents": "Restriction endonuclease cleavage map of the DNA of JC virus. A physical map of the sites cleaved by the following restriction endonucleases was derived for the DNA of JC virus, a human polyomavirus: EcoRI, HpaI, and PstI (one site each); HindII (four sites); and HindIII (three sites). By agarose gel electrophoresis of fragmented DNA, the size of full-length DNA of JC virus was estimated to be 5,125 +/- 105 base pairs (98 +/- 2% of the length of simian virus 40 DNA)."}
{"id": "PMID:221678", "title": "Fractionation of two protein kinases from avian myeloblastosis virus and characterization of the protein kinase activity preferring basic phosphoacceptor proteins.", "content": "Two protein kinase activities were fractionated from purified virions of avian myeloblastosis virus. Distinguishing characteristics of these two protein kinases included: (i) their binding properties during purification by ion-exchange chromatography; (ii) their estimated molecular weights; and (iii) their phosphoacceptor protein specificities. The protein kinase that bound to the anion exchanger DEAE-cellulose (pH 7.2) had an estimated molecular weight of 60,000 to 64,000 and preferred basic phosphoacceptor proteins. The protein kinase that bound to the cation exchanger phosphocellulose (pH 7.2) had an estimated molecular weight of 42,000 to 46,000 and preferred acidic phosphoacceptor proteins. The protein kinase preferring basic phosphoacceptor proteins was further purified and characterized. Optimal transfer of phosphate catalyzed by this enzyme required a divalent metal ion, a sulfhydryl-reducing agent, and ATP as phosphate donor. GTP was not an effective phosphate donor at concentrations comparable to ATP; and the cyclic nucleotides cyclic AMP and cyclic GMP neither stimulated nor inhibited protein phosphorylation by the protein kinase. The specificity of the protein kinase for basic phosphoacceptor proteins extended to proteins from avian myeloblastosis virus, in that the neutral to basic virion proteins p12, p19, and p27 served as phosphate acceptors. In addition, the protein kinase also appeared to phosphorylate itself. The role(s) of this virion-associated protein kinase is discussed.", "contents": "Fractionation of two protein kinases from avian myeloblastosis virus and characterization of the protein kinase activity preferring basic phosphoacceptor proteins. Two protein kinase activities were fractionated from purified virions of avian myeloblastosis virus. Distinguishing characteristics of these two protein kinases included: (i) their binding properties during purification by ion-exchange chromatography; (ii) their estimated molecular weights; and (iii) their phosphoacceptor protein specificities. The protein kinase that bound to the anion exchanger DEAE-cellulose (pH 7.2) had an estimated molecular weight of 60,000 to 64,000 and preferred basic phosphoacceptor proteins. The protein kinase that bound to the cation exchanger phosphocellulose (pH 7.2) had an estimated molecular weight of 42,000 to 46,000 and preferred acidic phosphoacceptor proteins. The protein kinase preferring basic phosphoacceptor proteins was further purified and characterized. Optimal transfer of phosphate catalyzed by this enzyme required a divalent metal ion, a sulfhydryl-reducing agent, and ATP as phosphate donor. GTP was not an effective phosphate donor at concentrations comparable to ATP; and the cyclic nucleotides cyclic AMP and cyclic GMP neither stimulated nor inhibited protein phosphorylation by the protein kinase. The specificity of the protein kinase for basic phosphoacceptor proteins extended to proteins from avian myeloblastosis virus, in that the neutral to basic virion proteins p12, p19, and p27 served as phosphate acceptors. In addition, the protein kinase also appeared to phosphorylate itself. The role(s) of this virion-associated protein kinase is discussed."}
{"id": "PMID:221679", "title": "Multiple forms of polyoma virus tumor antigens from infected and transformed cells.", "content": "At least three distinct forms of polyoma virus tumor antigens were isolated from productively infected and transformed hamster cells by immunoprecipitation with anti-T serum. These proteins had approximate molecular weights of 105,000 (large T antigen), 63,000 (middle T antigen), and 20,000 (small T antigen) as estimated by acrylamide gel electrophoresis. An examination of the appearance of these antigens in polyoma-infected mouse cells showed that all three polypeptides were synthesized maximally at approximately the same time after infection. Analysis of the methionine-containing tryptic peptides of these proteins indicated that the large, middle, and small forms of polyoma T antigens contained five similar or identical peptides. In addition, the 63,000- and 20,000-dalton antigens contained two other methionine peptides absent from the large T-antigen species. Other methionine peptides were found only in the large or middle T-antigen forms. These results and results obtained previously suggested that the three T-antigen species have the same NH2-terminal end regions but different COOH termini. A model is presented describing the synthesis of these polypeptides from different regions of the polyoma virus genome.", "contents": "Multiple forms of polyoma virus tumor antigens from infected and transformed cells. At least three distinct forms of polyoma virus tumor antigens were isolated from productively infected and transformed hamster cells by immunoprecipitation with anti-T serum. These proteins had approximate molecular weights of 105,000 (large T antigen), 63,000 (middle T antigen), and 20,000 (small T antigen) as estimated by acrylamide gel electrophoresis. An examination of the appearance of these antigens in polyoma-infected mouse cells showed that all three polypeptides were synthesized maximally at approximately the same time after infection. Analysis of the methionine-containing tryptic peptides of these proteins indicated that the large, middle, and small forms of polyoma T antigens contained five similar or identical peptides. In addition, the 63,000- and 20,000-dalton antigens contained two other methionine peptides absent from the large T-antigen species. Other methionine peptides were found only in the large or middle T-antigen forms. These results and results obtained previously suggested that the three T-antigen species have the same NH2-terminal end regions but different COOH termini. A model is presented describing the synthesis of these polypeptides from different regions of the polyoma virus genome."}
{"id": "PMID:221680", "title": "Mapping and ordering of fragments of BK virus DNA produced by restriction endonucleases.", "content": "A total of 51 restriction sites were recognized within the BK virus genome by the combination of 10 different restriction endonucleases. These sites were mapped and oriented relative to one another as well as to the five fragments generated by the digestion of BK virus DNA with HindIII and EcoRI. The result was a comprehensive physical map suitable for in-depth characterization of the functions of BK virus at the molecular level.", "contents": "Mapping and ordering of fragments of BK virus DNA produced by restriction endonucleases. A total of 51 restriction sites were recognized within the BK virus genome by the combination of 10 different restriction endonucleases. These sites were mapped and oriented relative to one another as well as to the five fragments generated by the digestion of BK virus DNA with HindIII and EcoRI. The result was a comprehensive physical map suitable for in-depth characterization of the functions of BK virus at the molecular level."}
{"id": "PMID:221681", "title": "Production of avian oncoviral subgroups after multiple infection.", "content": "The number of different oncoviral env genes that can be expressed by a single chicken embryo fibroblast was investigated. Fibroblasts were infected with one to three subgroups of Rous-associated virus, which is a nontransforming avian oncovirus, then superinfected with a transforming virus, Rous sarcoma virus, of a different subgroup. The subgroups of viruses released by the resulting clones were analyzed. When two viral subgroups were used for preinfection, all the resulting clones produced transforming virus particles having the subgroup of the superinfecting virus, and most clones produced transforming virus particles of all the infecting viral subgroups. However, when cells were preinfected with three viral subgroups, many of the resulting clones did not produce transforming virus particles having the subgroup of the superinfecting virus, and only 1 of 23 clones produced transforming particles of all the infecting viral subgroups. DNA annealing experiments showed that cells infected with three or four viral subgroups had an additional 8 to 20 copies of proviral DNA per cell. Finally, most clones resulting from cells simultaneously infected with three or four viral subgroups were able to produce virus of all infecting subgroups. It appears that the number of exogenous oncoviral env genes that can be expressed by a single cell is limited, and in the range of 4 to 8-20 per cell.", "contents": "Production of avian oncoviral subgroups after multiple infection. The number of different oncoviral env genes that can be expressed by a single chicken embryo fibroblast was investigated. Fibroblasts were infected with one to three subgroups of Rous-associated virus, which is a nontransforming avian oncovirus, then superinfected with a transforming virus, Rous sarcoma virus, of a different subgroup. The subgroups of viruses released by the resulting clones were analyzed. When two viral subgroups were used for preinfection, all the resulting clones produced transforming virus particles having the subgroup of the superinfecting virus, and most clones produced transforming virus particles of all the infecting viral subgroups. However, when cells were preinfected with three viral subgroups, many of the resulting clones did not produce transforming virus particles having the subgroup of the superinfecting virus, and only 1 of 23 clones produced transforming particles of all the infecting viral subgroups. DNA annealing experiments showed that cells infected with three or four viral subgroups had an additional 8 to 20 copies of proviral DNA per cell. Finally, most clones resulting from cells simultaneously infected with three or four viral subgroups were able to produce virus of all infecting subgroups. It appears that the number of exogenous oncoviral env genes that can be expressed by a single cell is limited, and in the range of 4 to 8-20 per cell."}
{"id": "PMID:221682", "title": "Messenger activity of virion RNA for avian leukosis viral envelope glycoprotein.", "content": "An intracellular assay for viral envelope glycoprotein (env) messenger was employed to analyze the RNA from virus particles of Rous-associated virus type 2. For this assay RNA was microinjected into cells infected by the env-deficient Bryan strain of Rous sarcoma virus [RSV(-) cells]. Only when the injected RNA could be translated by the recipient cells to produce viral envelope glycoprotein was the env deficiency of the RSV(-) cells complemented, enabling them to release focus-forming virus. RNA in a 21S size fraction from the Rous-associated virus particle promoted the release of numerous focus-forming virus from RSV(-) cells, whereas the major 35S virion RNA species was inactive. The env messenger activity sedimented as a sharp peak with high specific activity. RNase T1-generated fragments of virion 35S RNA were unable to promote the release of infectious virus from RSV(-) cells. Consequently, the active molecule was most likely to be env messenger which had been encapsulated by the virus particle from the cytoplasm of infected cells. Approximately 95% of the env messenger within the virion was associated with the virion high-molecular-weight RNA complex. The temperature required to dissociate env messenger from the high-molecular-weight complex was indistinguishable from the temperature required to disrupt the complex itself. Virion high-molecular-weight RNA that was associated with env messenger sedimented slightly more rapidly than the bulk virion RNA; this was the strongest evidence that the 21S messenger had been encapsulated directly from the infected cells. These data are considered along with a related observation [concerning the prolonged expression of env messenger after injection into RSV(-) cells] to raise the possibility that virus-encapsulated env messenger can become expressed within subsequently infected cells.", "contents": "Messenger activity of virion RNA for avian leukosis viral envelope glycoprotein. An intracellular assay for viral envelope glycoprotein (env) messenger was employed to analyze the RNA from virus particles of Rous-associated virus type 2. For this assay RNA was microinjected into cells infected by the env-deficient Bryan strain of Rous sarcoma virus [RSV(-) cells]. Only when the injected RNA could be translated by the recipient cells to produce viral envelope glycoprotein was the env deficiency of the RSV(-) cells complemented, enabling them to release focus-forming virus. RNA in a 21S size fraction from the Rous-associated virus particle promoted the release of numerous focus-forming virus from RSV(-) cells, whereas the major 35S virion RNA species was inactive. The env messenger activity sedimented as a sharp peak with high specific activity. RNase T1-generated fragments of virion 35S RNA were unable to promote the release of infectious virus from RSV(-) cells. Consequently, the active molecule was most likely to be env messenger which had been encapsulated by the virus particle from the cytoplasm of infected cells. Approximately 95% of the env messenger within the virion was associated with the virion high-molecular-weight RNA complex. The temperature required to dissociate env messenger from the high-molecular-weight complex was indistinguishable from the temperature required to disrupt the complex itself. Virion high-molecular-weight RNA that was associated with env messenger sedimented slightly more rapidly than the bulk virion RNA; this was the strongest evidence that the 21S messenger had been encapsulated directly from the infected cells. These data are considered along with a related observation [concerning the prolonged expression of env messenger after injection into RSV(-) cells] to raise the possibility that virus-encapsulated env messenger can become expressed within subsequently infected cells."}
{"id": "PMID:221683", "title": "Vesicular stomatitis virus glycoprotein is anchored to intracellular membranes near its carboxyl end and is proteolytically cleaved at its amino terminus.", "content": "The intracellular vesicular stomatitis virus glycoprotein (G) is inserted into membranes such that a small portion of one end of the molecule is exposed on the cytoplasmic surface of the endoplasmic reticulum and is susceptible to proteolytic digestion (T.G. Morrison, C.O. McQuain, and D. Simpson, J. Virol. 28:368-374). We have determined that this region of the G protein contains two methionyl tryptic peptides. The methionyl tryptic peptides of the G protein have been ordered by the use of the antibiotic pactamycin, and the two methionyl tryptic peptides removed by proteolytic digestion of intracellular G protein have been shown to be derived from the carboxyl terminal end of the protein. In addition, we have found that the unglycosylated G protein synthesized in a reticulocyte cell-free reaction migrates on polyacrylamide gels slightly slower than the unglycosylated G protein synthesized in tunicamycin-treated infected cells. We have also compared these G proteins derived from different sources by partial proteolysis (D.W. Cleveland, S.G. Fischer, M.W. Kirschner, and V.K. Laemmli, J. Biol. Chem. 252:1102-1106) and by chymotryptic peptide analysis. We have found minor differences between the two proteins consistent with the removal of 10 to 15 amino acids from the amino terminus of the intracellular G protein.", "contents": "Vesicular stomatitis virus glycoprotein is anchored to intracellular membranes near its carboxyl end and is proteolytically cleaved at its amino terminus. The intracellular vesicular stomatitis virus glycoprotein (G) is inserted into membranes such that a small portion of one end of the molecule is exposed on the cytoplasmic surface of the endoplasmic reticulum and is susceptible to proteolytic digestion (T.G. Morrison, C.O. McQuain, and D. Simpson, J. Virol. 28:368-374). We have determined that this region of the G protein contains two methionyl tryptic peptides. The methionyl tryptic peptides of the G protein have been ordered by the use of the antibiotic pactamycin, and the two methionyl tryptic peptides removed by proteolytic digestion of intracellular G protein have been shown to be derived from the carboxyl terminal end of the protein. In addition, we have found that the unglycosylated G protein synthesized in a reticulocyte cell-free reaction migrates on polyacrylamide gels slightly slower than the unglycosylated G protein synthesized in tunicamycin-treated infected cells. We have also compared these G proteins derived from different sources by partial proteolysis (D.W. Cleveland, S.G. Fischer, M.W. Kirschner, and V.K. Laemmli, J. Biol. Chem. 252:1102-1106) and by chymotryptic peptide analysis. We have found minor differences between the two proteins consistent with the removal of 10 to 15 amino acids from the amino terminus of the intracellular G protein."}
{"id": "PMID:221684", "title": "Defective retrovirus-like 30S RNA species of rat and mouse cells are infectious if packaged by type C helper virus.", "content": "RNA species with properties of defective retrovirus-like 30S RNA genomes have previously been detected in both rats and mice and in some rat and mouse retroviruses. Using cell lines which express high levels of this retrovirus-like RNA, we formed pseudotypes of the 30S RNAs with helper-independent type C viruses. A pseudotype virus complex containing a mouse 30S subunit was transmitted to rat cells, and a pseudotype virus complex containing a rat 30S subunit was transmitted to bat cells. In other transmission experiments, a rat 30S subunit was isolated in nonproducer bat cells without detectable expression of the helper-independent type C virus used to pseudotype it. The results provide further support for the retrovirus-like nature of the rat 30S subunit and provide evidence which supports the protovirus hypothesis proposed by Temin.", "contents": "Defective retrovirus-like 30S RNA species of rat and mouse cells are infectious if packaged by type C helper virus. RNA species with properties of defective retrovirus-like 30S RNA genomes have previously been detected in both rats and mice and in some rat and mouse retroviruses. Using cell lines which express high levels of this retrovirus-like RNA, we formed pseudotypes of the 30S RNAs with helper-independent type C viruses. A pseudotype virus complex containing a mouse 30S subunit was transmitted to rat cells, and a pseudotype virus complex containing a rat 30S subunit was transmitted to bat cells. In other transmission experiments, a rat 30S subunit was isolated in nonproducer bat cells without detectable expression of the helper-independent type C virus used to pseudotype it. The results provide further support for the retrovirus-like nature of the rat 30S subunit and provide evidence which supports the protovirus hypothesis proposed by Temin."}
{"id": "PMID:221685", "title": "Regulation of simian virus 40 early and late gene transcription without viral DNA replication.", "content": "Primary cultures of African green monkey kidney cells were infected with the simian virus 40 temperature-sensitive mutant tsA58 at the nonpermissive temperature of 41 degrees C for 12 to 20 h. Under these conditions, a defective T antigen was produced and no viral DNA replication was detected. Viral transcription complexes were extracted from infected nuclei using Sarkosyl and the nascent chains of RNA elongated in vitro. Sixty to 70% of the viral RNA synthesized in vitro hybridized to late gene sequences. In contrast, 80 to 90% of the nuclear viral RNA labeled in vivo during a 15-min pulse with [3H]uridine hybridized to early gene sequences. This suggests that selective degradation of late gene transcripts occurs in vivo. The role of T antigen and viral DNA replication in regulation of simian virus 40 transcription is discussed.", "contents": "Regulation of simian virus 40 early and late gene transcription without viral DNA replication. Primary cultures of African green monkey kidney cells were infected with the simian virus 40 temperature-sensitive mutant tsA58 at the nonpermissive temperature of 41 degrees C for 12 to 20 h. Under these conditions, a defective T antigen was produced and no viral DNA replication was detected. Viral transcription complexes were extracted from infected nuclei using Sarkosyl and the nascent chains of RNA elongated in vitro. Sixty to 70% of the viral RNA synthesized in vitro hybridized to late gene sequences. In contrast, 80 to 90% of the nuclear viral RNA labeled in vivo during a 15-min pulse with [3H]uridine hybridized to early gene sequences. This suggests that selective degradation of late gene transcripts occurs in vivo. The role of T antigen and viral DNA replication in regulation of simian virus 40 transcription is discussed."}
{"id": "PMID:221686", "title": "Biological activity of polyoma viral DNA in mice and hamsters.", "content": "The biological activity of polyoma viral DNA was evaluated in mice and hamsters. Viral DNA administered parenterally is about 4 to 5 logs less efficient than polyoma virions in establishing infection in mice. Supercoiled viral DNA was infectious for mice after parenteral administration, giving mean infective doses of 10(-3) to 10(-4) microgram. However, animals fed microgram quantities of polyoma DNA I did not become infected. Linearization of viral DNA with R.EcoRI or R.BamHI, which are single-cut enzymes cleaving in the early and late regions of the genome, respectively, reduced the infectivity for mice approximately fivefold. Approximately 10% of newborn hamsters inoculated intraperitoneally with polyoma DNA I developed tumors. In contrast, the same amount of viral DNA which had been cleaved in the early region with R.EcoRI induced tumors in 50% of inoculated hamsters.", "contents": "Biological activity of polyoma viral DNA in mice and hamsters. The biological activity of polyoma viral DNA was evaluated in mice and hamsters. Viral DNA administered parenterally is about 4 to 5 logs less efficient than polyoma virions in establishing infection in mice. Supercoiled viral DNA was infectious for mice after parenteral administration, giving mean infective doses of 10(-3) to 10(-4) microgram. However, animals fed microgram quantities of polyoma DNA I did not become infected. Linearization of viral DNA with R.EcoRI or R.BamHI, which are single-cut enzymes cleaving in the early and late regions of the genome, respectively, reduced the infectivity for mice approximately fivefold. Approximately 10% of newborn hamsters inoculated intraperitoneally with polyoma DNA I developed tumors. In contrast, the same amount of viral DNA which had been cleaved in the early region with R.EcoRI induced tumors in 50% of inoculated hamsters."}
{"id": "PMID:221691", "title": "Successful treatment of human genital herpes infections with 2-deoxy-D-glucose.", "content": "Thirty-six women with genital herpes infections (proved by virological or cytological means) were treated in a double-blind placebo-controlled study with the glucose analogue 2-deoxy-D-glucose for a three-week period. In initial mucocutaneous cases, 89% were cured, with two recurrences after 24 months; in the case of recurrent or secondary infections, 90% had a notable improvement manifested by no or less-frequent recurrences, fewer lesions, or shortened duration of symptoms. In initial infections, discomfort cleared within 12 to 72 hours of therapy; 90% of the patients were asymptomatic within four days. In both cases, virus shedding was notably reduced by 2-deoxy-D-glucose. Concomitant controls treated with placebos failed to respond within this time frame. The use of 2-deoxy-D-glucose provides a simple and unique approach to the treatment of genital herpesvirus infections.", "contents": "Successful treatment of human genital herpes infections with 2-deoxy-D-glucose. Thirty-six women with genital herpes infections (proved by virological or cytological means) were treated in a double-blind placebo-controlled study with the glucose analogue 2-deoxy-D-glucose for a three-week period. In initial mucocutaneous cases, 89% were cured, with two recurrences after 24 months; in the case of recurrent or secondary infections, 90% had a notable improvement manifested by no or less-frequent recurrences, fewer lesions, or shortened duration of symptoms. In initial infections, discomfort cleared within 12 to 72 hours of therapy; 90% of the patients were asymptomatic within four days. In both cases, virus shedding was notably reduced by 2-deoxy-D-glucose. Concomitant controls treated with placebos failed to respond within this time frame. The use of 2-deoxy-D-glucose provides a simple and unique approach to the treatment of genital herpesvirus infections."}
{"id": "PMID:221694", "title": "Clinical application of measurement of angiotensin-converting enzyme level.", "content": "Assay of angiotensin-converting enzyme (ACE) in the sera of 69 patients demonstrated elevated levels in 19 of 22 (86%) of those with clinically active, biopsy-proved sarcoidosis. Patients with dormant sarcoidosis and generally those with various other disorders had normal levels. Elevated levels were also seen in six cases possibly representing sarcoid variants and in one case each of leprosy, carcinoma, tuberculosis, lymphomatoid granulomatosis, and immunoblastic sarcoma. Although ACE is sensitive to active sarcoidosis, the presence of false-positive findings limits its diagnostic usefulness to an adjunctive role; the assay should be combined with medical evaluation and tissue biopsy in selected cases.", "contents": "Clinical application of measurement of angiotensin-converting enzyme level. Assay of angiotensin-converting enzyme (ACE) in the sera of 69 patients demonstrated elevated levels in 19 of 22 (86%) of those with clinically active, biopsy-proved sarcoidosis. Patients with dormant sarcoidosis and generally those with various other disorders had normal levels. Elevated levels were also seen in six cases possibly representing sarcoid variants and in one case each of leprosy, carcinoma, tuberculosis, lymphomatoid granulomatosis, and immunoblastic sarcoma. Although ACE is sensitive to active sarcoidosis, the presence of false-positive findings limits its diagnostic usefulness to an adjunctive role; the assay should be combined with medical evaluation and tissue biopsy in selected cases."}
{"id": "PMID:221695", "title": "Exposure to polybrominated biphenyls. Some effects on personality and cognitive functioning.", "content": "Twenty-one persons exposed to polybrominated biphenyls (PBB) were compared with hospital volunteers on a battery of tests measuring memory, motor strength and coordination, cortical-sensory perception, personality, and higher cognitive functioning. Patients exposed to PBB were selected for this study only if they had persistent medical complaints. The PBB adipose levels did not correlate with performance on any test in the battery. The two groups did differ on the Minnesota Multiphasic Personality Inventory, suggesting an adjustment reaction with depressive symptoms and somatizing defenses. Persons exposed to PBB were also impaired relative to control subjects on tests of prose recall, short-term memory, concentration, and cognitive flexibility. However these differences vanished when group differences on education and personality were statistically held constant. The selective admission criteria for this study limit the generalizability of these findings.", "contents": "Exposure to polybrominated biphenyls. Some effects on personality and cognitive functioning. Twenty-one persons exposed to polybrominated biphenyls (PBB) were compared with hospital volunteers on a battery of tests measuring memory, motor strength and coordination, cortical-sensory perception, personality, and higher cognitive functioning. Patients exposed to PBB were selected for this study only if they had persistent medical complaints. The PBB adipose levels did not correlate with performance on any test in the battery. The two groups did differ on the Minnesota Multiphasic Personality Inventory, suggesting an adjustment reaction with depressive symptoms and somatizing defenses. Persons exposed to PBB were also impaired relative to control subjects on tests of prose recall, short-term memory, concentration, and cognitive flexibility. However these differences vanished when group differences on education and personality were statistically held constant. The selective admission criteria for this study limit the generalizability of these findings."}
{"id": "PMID:221698", "title": "Epidemiology of hepatocellular adenoma. The role of oral contraceptive use.", "content": "A case-control study of hepatocellular adenoma (HCA), a serious though nonmalignant liver tumor, was conducted by the Center for Disease Control and the Armed Forces Institute of Pathology (AFIP). Interviews with 79 women with HCA and with 220 age- and neighborhood-matched controls were completed. Limited information was obtained on nine additional patients who had died. Women with HCA and hemorrhage have a greater risk of morbidity and death than those with other symptoms. Increasing duration of OC use increases the risk of HCA. Use of OCs with high hormonal potency and age over 30 years may further increase a woman's risk of HCA. Long-term users of OCs have an estimated annual incidence of HCA of 3 to 4 per 100,000.", "contents": "Epidemiology of hepatocellular adenoma. The role of oral contraceptive use. A case-control study of hepatocellular adenoma (HCA), a serious though nonmalignant liver tumor, was conducted by the Center for Disease Control and the Armed Forces Institute of Pathology (AFIP). Interviews with 79 women with HCA and with 220 age- and neighborhood-matched controls were completed. Limited information was obtained on nine additional patients who had died. Women with HCA and hemorrhage have a greater risk of morbidity and death than those with other symptoms. Increasing duration of OC use increases the risk of HCA. Use of OCs with high hormonal potency and age over 30 years may further increase a woman's risk of HCA. Long-term users of OCs have an estimated annual incidence of HCA of 3 to 4 per 100,000."}
{"id": "PMID:221699", "title": "Factors influencing essential fatty acid requirement in total parenteral nutrition (TPN).", "content": "Twenty patients, after major injuries or elective abdominal surgery, were studied with respect to essential fatty acids in total serum and lipoprotein fractions. The regimen of total parenteral nutrition was altered in its content of energy, carbohydrates or fat. In all patients the linoleic acid levels decreased and the 20:3/20:4 ratio increased. Serum low density lipoproteins developed remarkable alterations of the biochemical composition and of morphology by electronmicroscopy. The degree of these alterations depended on the kind of illness, the amount of carbohydrates infused, special hormonal situation due to surgery and linoleic acid supply. As a consequence of these results, the supply of a sufficient amount of linoleic acid should be considered in every case of total parenteral nutrition.", "contents": "Factors influencing essential fatty acid requirement in total parenteral nutrition (TPN). Twenty patients, after major injuries or elective abdominal surgery, were studied with respect to essential fatty acids in total serum and lipoprotein fractions. The regimen of total parenteral nutrition was altered in its content of energy, carbohydrates or fat. In all patients the linoleic acid levels decreased and the 20:3/20:4 ratio increased. Serum low density lipoproteins developed remarkable alterations of the biochemical composition and of morphology by electronmicroscopy. The degree of these alterations depended on the kind of illness, the amount of carbohydrates infused, special hormonal situation due to surgery and linoleic acid supply. As a consequence of these results, the supply of a sufficient amount of linoleic acid should be considered in every case of total parenteral nutrition."}
{"id": "PMID:221700", "title": "Cardiovascular effects of exercise in hamsters with experimental thiamine deficiency.", "content": "The hemodynamic effects of daily treadmill exercise were evaluated in hamsters with experimental thiamine deficiency to test the hypothesis that increased energy consumption might be a contributory factor in the pathogenesis of beriberi heart disease. Daily exercise enhanced thiamine deficiency and was manifested by earlier development of symptoms of neuropathy compared to non-exercised animals. Hemodynamics of exercised thiamine deficient animals were characterized by significantly lower O2 consumption, lower cardiac output, and lower left ventricular minute work, compared to exercised, pair-fed control animals. Left ventricular end-diastolic pressure was slightly but not significantly higher in thiamine deficient animals. Left ventricular function, therefore, was depressed in this group. There was no evidence of hyperkinetic circulation, cardiomegaly or congestive heart failure. Neuropathy and depressed ventricular function, characteristic of pure thiamine deficiency, were observed in the absence of high cardiac output or high output failure, the pathogenesis of which may require other unknown factors.", "contents": "Cardiovascular effects of exercise in hamsters with experimental thiamine deficiency. The hemodynamic effects of daily treadmill exercise were evaluated in hamsters with experimental thiamine deficiency to test the hypothesis that increased energy consumption might be a contributory factor in the pathogenesis of beriberi heart disease. Daily exercise enhanced thiamine deficiency and was manifested by earlier development of symptoms of neuropathy compared to non-exercised animals. Hemodynamics of exercised thiamine deficient animals were characterized by significantly lower O2 consumption, lower cardiac output, and lower left ventricular minute work, compared to exercised, pair-fed control animals. Left ventricular end-diastolic pressure was slightly but not significantly higher in thiamine deficient animals. Left ventricular function, therefore, was depressed in this group. There was no evidence of hyperkinetic circulation, cardiomegaly or congestive heart failure. Neuropathy and depressed ventricular function, characteristic of pure thiamine deficiency, were observed in the absence of high cardiac output or high output failure, the pathogenesis of which may require other unknown factors."}
{"id": "PMID:221701", "title": "Concentration of myocardial cyclic AMP and ventricular fibrillation induced by aminophylline.", "content": "The concentration of myocardial cyclic AMP was measured in 9 dogs by radioimmunoassay after the administration of aminophylline. Fourteen dogs served as control. The concentration of cyclic AMP in the left ventricle was the highest and the lowest value was obtained in the right atrium in the control dogs. Ventricular fibrillations were induced immediately after the injection of 30 mg/Kg aminophylline in 3 dogs out of 9. The concentration of the left ventricular cyclic AMP in 6 dogs which tolerated aminophylline was significantly elevated compared with that of the control dogs (p less than 0.05). The left ventricular cyclic AMP in 3 dogs with ventricular fibrillation was significantly higher compared with that in the aminophylline tolerated dogs with non-fibrillating hearts (p less than 0.01). These results showed that the concentration of cyclic AMP was elevated in the fibrillating heart.", "contents": "Concentration of myocardial cyclic AMP and ventricular fibrillation induced by aminophylline. The concentration of myocardial cyclic AMP was measured in 9 dogs by radioimmunoassay after the administration of aminophylline. Fourteen dogs served as control. The concentration of cyclic AMP in the left ventricle was the highest and the lowest value was obtained in the right atrium in the control dogs. Ventricular fibrillations were induced immediately after the injection of 30 mg/Kg aminophylline in 3 dogs out of 9. The concentration of the left ventricular cyclic AMP in 6 dogs which tolerated aminophylline was significantly elevated compared with that of the control dogs (p less than 0.05). The left ventricular cyclic AMP in 3 dogs with ventricular fibrillation was significantly higher compared with that in the aminophylline tolerated dogs with non-fibrillating hearts (p less than 0.01). These results showed that the concentration of cyclic AMP was elevated in the fibrillating heart."}
{"id": "PMID:221708", "title": "Different effects of N-ethylmaleimide on the tension components of bullfrog atrium.", "content": "The effects of N-ethylmaleimide (NEM) on the tension components of bullfrog atrium were studied under voltage clamp conditions using the double sucrose gap technique. NEM at a dilution of 10(-3) M inhibited the ICa-independent tonic tension elicited by large and long depolarizing pulses (140 mV, 2 sec) time-dependently, whereas the drug produced an initial transient increase and a later decrease of the ICa-dependent phasic tension elicited by small and short depolarizing pulses (60 mV, 100 msec). The effect of NEM was facilitated when the atrial muscles were exposed to a solution having either a reduced Na or an increased Ca concentration. In the presence of Mn ions, 10(-3) M NEM did not evidently inhibit tonic tension, and it led to a slight transient increase in phasic tension. NEM at 10(-3) M, which is known to inhibit sarcolemmal Na, K-ATPase, enhanced both the phasic tension and the tonic tension in the presence of ouabain and when perfused with K-free solution. Even under these conditions (10(-3) M NEM caused an initial transient decrease of ICa-independent tonic tension. This suggests that NEM has a different action on the atrial muscle from those of cardiac glycosides such as ouabain.", "contents": "Different effects of N-ethylmaleimide on the tension components of bullfrog atrium. The effects of N-ethylmaleimide (NEM) on the tension components of bullfrog atrium were studied under voltage clamp conditions using the double sucrose gap technique. NEM at a dilution of 10(-3) M inhibited the ICa-independent tonic tension elicited by large and long depolarizing pulses (140 mV, 2 sec) time-dependently, whereas the drug produced an initial transient increase and a later decrease of the ICa-dependent phasic tension elicited by small and short depolarizing pulses (60 mV, 100 msec). The effect of NEM was facilitated when the atrial muscles were exposed to a solution having either a reduced Na or an increased Ca concentration. In the presence of Mn ions, 10(-3) M NEM did not evidently inhibit tonic tension, and it led to a slight transient increase in phasic tension. NEM at 10(-3) M, which is known to inhibit sarcolemmal Na, K-ATPase, enhanced both the phasic tension and the tonic tension in the presence of ouabain and when perfused with K-free solution. Even under these conditions (10(-3) M NEM caused an initial transient decrease of ICa-independent tonic tension. This suggests that NEM has a different action on the atrial muscle from those of cardiac glycosides such as ouabain."}
{"id": "PMID:221709", "title": "Changes in adipocyte beta-adrenergic receptor of cold-acclimated rats.", "content": "The changes in the number and affinity of binding sites in the beta-adrenergic receptors of rat white adipocytes after cold exposure were studied with the aid of (p)-[3H]dihydroalprenolol. One day cold exposure did not change the number and affinity of binding sites in beta-adrenergic receptors. Chronic exposure of rats to cold (5 degrees C) for 1 and 4 weeks significantly decreased the affinity of beta-adrenergic receptors without any alteration in the number of binding sites. Such changes in the binding affinity observed in cold-acclimated rats (4 weeks, 5 degrees C) remained for 18 hr after these animals were transferred to a warm environment of 25 degrees C. The decreased affinity of binding sites in beta-adrenergic receptor induced by cold acclimation could not explain the enhanced metabolic response of cold-acclimated animals to noradrenaline.", "contents": "Changes in adipocyte beta-adrenergic receptor of cold-acclimated rats. The changes in the number and affinity of binding sites in the beta-adrenergic receptors of rat white adipocytes after cold exposure were studied with the aid of (p)-[3H]dihydroalprenolol. One day cold exposure did not change the number and affinity of binding sites in beta-adrenergic receptors. Chronic exposure of rats to cold (5 degrees C) for 1 and 4 weeks significantly decreased the affinity of beta-adrenergic receptors without any alteration in the number of binding sites. Such changes in the binding affinity observed in cold-acclimated rats (4 weeks, 5 degrees C) remained for 18 hr after these animals were transferred to a warm environment of 25 degrees C. The decreased affinity of binding sites in beta-adrenergic receptor induced by cold acclimation could not explain the enhanced metabolic response of cold-acclimated animals to noradrenaline."}
{"id": "PMID:221710", "title": "Remnant liver function during surgery for extensive hepatic resection.", "content": "True functional reserve of remnant liver should be determined at the same condition that contemplated hepatectomy has been performed, and this condition can be achieved before resection by temporary clamping of the inflow vessels of hepatic lobes to be removed. Using indocyanine green (ICG), the remnant liver function (RLF) was evaluated whether or not the method can be a useful indicator for or against hepatomy. In the study of healthy dogs, the RLF proved to be a reliable indicator to prospect hepatic failure which may occur after extensive resection of the liver. Then, the method was employed in nine patients who underwent 40 to 70 per cent hepatectomy. The results indicated that the RLF with ICG during surgery, if performed under stable hemodynamics, is a beneficial tool to decide the resectability in equivocal cases.", "contents": "Remnant liver function during surgery for extensive hepatic resection. True functional reserve of remnant liver should be determined at the same condition that contemplated hepatectomy has been performed, and this condition can be achieved before resection by temporary clamping of the inflow vessels of hepatic lobes to be removed. Using indocyanine green (ICG), the remnant liver function (RLF) was evaluated whether or not the method can be a useful indicator for or against hepatomy. In the study of healthy dogs, the RLF proved to be a reliable indicator to prospect hepatic failure which may occur after extensive resection of the liver. Then, the method was employed in nine patients who underwent 40 to 70 per cent hepatectomy. The results indicated that the RLF with ICG during surgery, if performed under stable hemodynamics, is a beneficial tool to decide the resectability in equivocal cases."}
{"id": "PMID:221713", "title": "Polyoncogenicity and insulinoma-inducing ability of BK Virus, a human Papovavirus, in Syrian golden hamsters.", "content": "Newborn hamsters were inoculated intracerebrally with a series of purified and concentrated BK virus samples originating from a single stock of Gardner's original strain. Most (60-100%) of the hamsters developed various tumors 3-9 months later. The frequent types of tumors were ventricular tumors (choroid plexus papillomas and ependymomas: 7-53%), malignant insulinomas (0-92%), and osteosarcomas (0-50%). The T-antigen was positive in 59 of 60 tumors tested, but the virus was rescued by the cell fusion method from only 1 of 11 cell lines derived from these tumors. The incidence of insulinomas varied greatly with the virus sample; the two samples that showed the highest incidence (47 and 92%) originated from one parental virus stock, and all the other samples with the lower incidences (0-9%) originated from another ancestral stock. These results suggest the presence of a BK virus mutant(s) differing in capacity to induce insulinoma. A functional insulinoma cell line was thus established.", "contents": "Polyoncogenicity and insulinoma-inducing ability of BK Virus, a human Papovavirus, in Syrian golden hamsters. Newborn hamsters were inoculated intracerebrally with a series of purified and concentrated BK virus samples originating from a single stock of Gardner's original strain. Most (60-100%) of the hamsters developed various tumors 3-9 months later. The frequent types of tumors were ventricular tumors (choroid plexus papillomas and ependymomas: 7-53%), malignant insulinomas (0-92%), and osteosarcomas (0-50%). The T-antigen was positive in 59 of 60 tumors tested, but the virus was rescued by the cell fusion method from only 1 of 11 cell lines derived from these tumors. The incidence of insulinomas varied greatly with the virus sample; the two samples that showed the highest incidence (47 and 92%) originated from one parental virus stock, and all the other samples with the lower incidences (0-9%) originated from another ancestral stock. These results suggest the presence of a BK virus mutant(s) differing in capacity to induce insulinoma. A functional insulinoma cell line was thus established."}
{"id": "PMID:221714", "title": "Loss of strain specificity of the TA3-St subline: evidence for the role of epiglycanin in mouse allogeneic tumor growth.", "content": "We described the in vivo conversion of the strain-specific ascites murine mammary adenocarcinoma subline TA3-St to a new ascites subline designated TA3-MM. This conversion occurred during passage in a syngeneic A/HeHa mouse infected with pneumonia-producing microorganisms. The mode number of chromosomes of the TA3-MM cell (82) was greater than that of the parental TA3-St cell (69) or the other non-strain-specific subline TA3-Ha (42). The TA3-MM subline could grow in and kill mice of various allogeneic strains. In addition, the TA3-MM cell possessed numerous receptors for the lectin of Vicia graminea seeds, which were hardly detectable at the surface of the parent TA3-St subline but were present in abundance at the cell surface of the non-strain-specific subline TA3-Ha. These lectin receptors of the TA3-Ha cell were previously demonstrated to be present in a unique high-molecular-weight endogenous cell surface glycoprotein termed epiglycanin. The V. gramines lectin receptors on the new TA3-MM subline also were present on an epiglycanin-like molecule. This finding provides further evidence for the hypothesis that allogeneic growth in the TA3 system is a direct result of these membrane glycoproteins.", "contents": "Loss of strain specificity of the TA3-St subline: evidence for the role of epiglycanin in mouse allogeneic tumor growth. We described the in vivo conversion of the strain-specific ascites murine mammary adenocarcinoma subline TA3-St to a new ascites subline designated TA3-MM. This conversion occurred during passage in a syngeneic A/HeHa mouse infected with pneumonia-producing microorganisms. The mode number of chromosomes of the TA3-MM cell (82) was greater than that of the parental TA3-St cell (69) or the other non-strain-specific subline TA3-Ha (42). The TA3-MM subline could grow in and kill mice of various allogeneic strains. In addition, the TA3-MM cell possessed numerous receptors for the lectin of Vicia graminea seeds, which were hardly detectable at the surface of the parent TA3-St subline but were present in abundance at the cell surface of the non-strain-specific subline TA3-Ha. These lectin receptors of the TA3-Ha cell were previously demonstrated to be present in a unique high-molecular-weight endogenous cell surface glycoprotein termed epiglycanin. The V. gramines lectin receptors on the new TA3-MM subline also were present on an epiglycanin-like molecule. This finding provides further evidence for the hypothesis that allogeneic growth in the TA3 system is a direct result of these membrane glycoproteins."}
{"id": "PMID:221715", "title": "Lymphoid neoplasms in chicken flocks free of infection with exogenous avian tumor viruses.", "content": "More than 4,500 breeding female chickens of nine inbred lines maintained under specific-pathogen-free conditions to approximately 500 days of age were studied. Routine monitoring and special assays indicated that they were free of infection by exogenous viruses of the leukosis-sarcoma and the reticuloendotheliosis groups. Some birds were maintained free of Marek's disease (MD) virus infection in plastic isolators, and others were maintained in conventional chicken houses and vaccinated with the herpesvirus of turkeys to prevent the lesions of MD. Ten birds bearing lymphoid tumors were observed in two sublines of one line of chickens known to produce embryos that spontaneously produce Rous-associated virus, type 0 (RAV-O), an endogenous virus of the chicken. Four tumors were found in chickens of one subline maintained free of MD virus infection in isolators. These tumors did not involve the bursa and had some histologic features different from those typical of lymphoid leukosis. Six tumors were found in chickens of the other subline that were vaccinated to prevent MD; these tumors involved the bursa and were typical of lymphoid leukosis but not MD. These results suggest that two types of tumors may have been observed. The fact that DNA extracted from both types of tumors did not contain exogenous lymphoid leukosis virus sequences confirms the virologic evidence that exogenous viruses were not involved. The fact that endogenous viral sequences were not increased in copy number suggests that the endogenous virus RAV-O did not directly induce the tumors. Two birds with tumors not involving the bursa were found alive, and transplantable lymphoid tumors were developed. These tumors were of T-cell origin rather than of bursa cell origin as would be expected of lymphoid leukosis. These are the first reported lymphoid tumors that have been observed in the absence of known exogenous tumor virus infection in chickens. Our evidence suggests that the endogenous virus RAV-O did not play a primary role in the induction of these tumors.", "contents": "Lymphoid neoplasms in chicken flocks free of infection with exogenous avian tumor viruses. More than 4,500 breeding female chickens of nine inbred lines maintained under specific-pathogen-free conditions to approximately 500 days of age were studied. Routine monitoring and special assays indicated that they were free of infection by exogenous viruses of the leukosis-sarcoma and the reticuloendotheliosis groups. Some birds were maintained free of Marek's disease (MD) virus infection in plastic isolators, and others were maintained in conventional chicken houses and vaccinated with the herpesvirus of turkeys to prevent the lesions of MD. Ten birds bearing lymphoid tumors were observed in two sublines of one line of chickens known to produce embryos that spontaneously produce Rous-associated virus, type 0 (RAV-O), an endogenous virus of the chicken. Four tumors were found in chickens of one subline maintained free of MD virus infection in isolators. These tumors did not involve the bursa and had some histologic features different from those typical of lymphoid leukosis. Six tumors were found in chickens of the other subline that were vaccinated to prevent MD; these tumors involved the bursa and were typical of lymphoid leukosis but not MD. These results suggest that two types of tumors may have been observed. The fact that DNA extracted from both types of tumors did not contain exogenous lymphoid leukosis virus sequences confirms the virologic evidence that exogenous viruses were not involved. The fact that endogenous viral sequences were not increased in copy number suggests that the endogenous virus RAV-O did not directly induce the tumors. Two birds with tumors not involving the bursa were found alive, and transplantable lymphoid tumors were developed. These tumors were of T-cell origin rather than of bursa cell origin as would be expected of lymphoid leukosis. These are the first reported lymphoid tumors that have been observed in the absence of known exogenous tumor virus infection in chickens. Our evidence suggests that the endogenous virus RAV-O did not play a primary role in the induction of these tumors."}
{"id": "PMID:221716", "title": "Induction of B-tropic and N-tropic murine leukemia virus from B10.BR/SgLi mouse embryo cell lines by 5-iodo-2'-deoxyuridine.", "content": "In contrast to the original B10.BR/SgSn congenic mouse strain, adult mice of the B10.BR/SgLi subline showed a high level of expression of B-tropic ecotropic murine leukemia virus (MuLV). Both B-tropic and N-tropic ecotropic MuLV could be included in cultures of virus-free cell lines derived from embryos of B10.BR/SgLi mice. Both various were also inducible from each of several clonal cell lines and from cultures of F1 embryos of matings of B10.BR/SgLi males with females of strains NFS/N and A/J, which are negative for B-tropic virus. Thus the information for B-tropic MuLV as well as that for N-tropic MuLV was transmitted as a genetic element in the B10.BR/SgLi subline.", "contents": "Induction of B-tropic and N-tropic murine leukemia virus from B10.BR/SgLi mouse embryo cell lines by 5-iodo-2'-deoxyuridine. In contrast to the original B10.BR/SgSn congenic mouse strain, adult mice of the B10.BR/SgLi subline showed a high level of expression of B-tropic ecotropic murine leukemia virus (MuLV). Both B-tropic and N-tropic ecotropic MuLV could be included in cultures of virus-free cell lines derived from embryos of B10.BR/SgLi mice. Both various were also inducible from each of several clonal cell lines and from cultures of F1 embryos of matings of B10.BR/SgLi males with females of strains NFS/N and A/J, which are negative for B-tropic virus. Thus the information for B-tropic MuLV as well as that for N-tropic MuLV was transmitted as a genetic element in the B10.BR/SgLi subline."}
{"id": "PMID:221717", "title": "Inhibitory effects of butylated hydroxyanisole on methylazoxymethanol acetate-induced neoplasia of the large intestine and on nicotinamide adenine dinucleotide-dependent alcohol dehydrogenase activity in mice.", "content": "Butylated hydroxyanisole (BHA), a widely used food additive, previously was found to inhibit various chemical carcinogens. In the present work, BHA, when added to the diet, inhibited the carcinogenic action of methylazoxymethanol (MAM) acetate on the large intestine of female CF1 mice. The effects of BHA on nicotinamide adenine dinucleotide (NAD+)-dependent alcohol dehydrogenase, a postulated activating enzyme for MAM, were determined. BHA reduced this enzyme activity in vitro in crude tissue preparations of large intestine and liver. The parallel finding of BHA inhibition of MAM acetate carcinogenesis of the large bowel and of NAD'-dependent dehydrogenase activity lends support to the postulated role of the dehydrogenase activity in activating MAM to an ultimate carcinogenic form. However, BHA has multiple biologic actions so that its inhibitory effect on MAM acetate-induced neoplasia of the large intestine may entail some other mechanism.", "contents": "Inhibitory effects of butylated hydroxyanisole on methylazoxymethanol acetate-induced neoplasia of the large intestine and on nicotinamide adenine dinucleotide-dependent alcohol dehydrogenase activity in mice. Butylated hydroxyanisole (BHA), a widely used food additive, previously was found to inhibit various chemical carcinogens. In the present work, BHA, when added to the diet, inhibited the carcinogenic action of methylazoxymethanol (MAM) acetate on the large intestine of female CF1 mice. The effects of BHA on nicotinamide adenine dinucleotide (NAD+)-dependent alcohol dehydrogenase, a postulated activating enzyme for MAM, were determined. BHA reduced this enzyme activity in vitro in crude tissue preparations of large intestine and liver. The parallel finding of BHA inhibition of MAM acetate carcinogenesis of the large bowel and of NAD'-dependent dehydrogenase activity lends support to the postulated role of the dehydrogenase activity in activating MAM to an ultimate carcinogenic form. However, BHA has multiple biologic actions so that its inhibitory effect on MAM acetate-induced neoplasia of the large intestine may entail some other mechanism."}
{"id": "PMID:221718", "title": "Detection of a human serum DNA-binding protein associated with malignant disease.", "content": "Human serum DNA-binding proteins were fractionated by DNA-cellulose affinity chromatography. Electrophoretic resolution of these protein fractions allowed the direct comparison of DNA-binding proteins from pools of serum from cancer patients, fetuses, or normal humans. A protein band detected in the fraction eluted by 0.6 M NaCl was elevated in pooled cancer serum, compared to normal or fetal serum. This malignant disease-associated DNA-binding protein (MAD-2) did not react with a variety of antisera directed against specific human serum proteins, blood components, or tumor markers. A chromatography-electrophoresis assay system for MAD-2 that allows the simultaneous determination of 20-30 serum samples was developed. This assay system was used for a preliminary clinical study, which revealed elevated MAD-2 levels in sera from pregnant women and individuals with various carcinomas, compared to levels in sera obtained from normal individuals, patients with nonmalignant diseases, or fetal cord samples.", "contents": "Detection of a human serum DNA-binding protein associated with malignant disease. Human serum DNA-binding proteins were fractionated by DNA-cellulose affinity chromatography. Electrophoretic resolution of these protein fractions allowed the direct comparison of DNA-binding proteins from pools of serum from cancer patients, fetuses, or normal humans. A protein band detected in the fraction eluted by 0.6 M NaCl was elevated in pooled cancer serum, compared to normal or fetal serum. This malignant disease-associated DNA-binding protein (MAD-2) did not react with a variety of antisera directed against specific human serum proteins, blood components, or tumor markers. A chromatography-electrophoresis assay system for MAD-2 that allows the simultaneous determination of 20-30 serum samples was developed. This assay system was used for a preliminary clinical study, which revealed elevated MAD-2 levels in sera from pregnant women and individuals with various carcinomas, compared to levels in sera obtained from normal individuals, patients with nonmalignant diseases, or fetal cord samples."}
{"id": "PMID:221719", "title": "Effect of low-dose-rate irradiation on the division potential of cells in vitro. V. Human skin fibroblasts from donors with a high risk of cancer.", "content": "Skin fibroblasts from normal donors, donors with ataxia-telangiectasia or Fanconi's anemia, and from 1 cancer patient were treated with repeated gamma-radiation at about 16 rads per hour. The remaining division potential of all fibroblasts, except for the Fanconi's anemia cells, was reduced to different extents by radiation. The growth potential of Fanconi's anemia cells was increased in all the irradiated cultures. The increase was 54% in the group that survived the longest. These results were identical to those obtained with fibroblasts from certain species that have a high probability of transformation.", "contents": "Effect of low-dose-rate irradiation on the division potential of cells in vitro. V. Human skin fibroblasts from donors with a high risk of cancer. Skin fibroblasts from normal donors, donors with ataxia-telangiectasia or Fanconi's anemia, and from 1 cancer patient were treated with repeated gamma-radiation at about 16 rads per hour. The remaining division potential of all fibroblasts, except for the Fanconi's anemia cells, was reduced to different extents by radiation. The growth potential of Fanconi's anemia cells was increased in all the irradiated cultures. The increase was 54% in the group that survived the longest. These results were identical to those obtained with fibroblasts from certain species that have a high probability of transformation."}
{"id": "PMID:221724", "title": "[Establishment of leukaemia cell lines and their significance for clinical and experimental oncology (author's transl)].", "content": "Permanent in vitro growing leukemic cell lines have been established from all types of immunologically classified childhood leukemias. Essential characteristics of primary blasts and cultured cells are identical. In contrast to lymphoblastoid, non-leukemic cell lines, the Epstein-Barr-virus specific nuclear angiten (EBNA) is not detected. Up to now 8 Non-B-non-T cell lines (6 of them were derived from children with acute lymphoblastic leukemia, 2 from patients with chronic myeloid leukemia), 8 T-lines and one B-line have been established. Three Non-B-non-T lines from children with acute lymphoblastic leukemia (KM-3, RU-3, MH-3) and one T-cell line (JM) were cultivated by ourselves. Cultured blasts represent a pure tumor material which can be propagated in large quantities. Leukemic cell lines reveal a new approach for the search after leukemia-associated proteins and represent another possibility for the experimental investigation of the etiology of leukemia.", "contents": "[Establishment of leukaemia cell lines and their significance for clinical and experimental oncology (author's transl)]. Permanent in vitro growing leukemic cell lines have been established from all types of immunologically classified childhood leukemias. Essential characteristics of primary blasts and cultured cells are identical. In contrast to lymphoblastoid, non-leukemic cell lines, the Epstein-Barr-virus specific nuclear angiten (EBNA) is not detected. Up to now 8 Non-B-non-T cell lines (6 of them were derived from children with acute lymphoblastic leukemia, 2 from patients with chronic myeloid leukemia), 8 T-lines and one B-line have been established. Three Non-B-non-T lines from children with acute lymphoblastic leukemia (KM-3, RU-3, MH-3) and one T-cell line (JM) were cultivated by ourselves. Cultured blasts represent a pure tumor material which can be propagated in large quantities. Leukemic cell lines reveal a new approach for the search after leukemia-associated proteins and represent another possibility for the experimental investigation of the etiology of leukemia."}
{"id": "PMID:221725", "title": "[Action of oxygen under increased pressure on the neutrophil metabolism in the peripheral blood].", "content": "The effect of hyperbaric oxygen (1--5 ata for 1 hr) on the activity of cytochrome oxidase, peroxidase, lipid content and phagocytic activity of neutrophils was studied. The dynamics of the recovery of those parameters was followed. A multimodal relationship between the pressure level and changes in the enzyme activity and lipid content was noted. The decrease in the activity of peroxidase was more pronounced than that of cytochrome oxidase in all cases. The dynamics of the recovery of the above parameters was shown to depend on the pressure level. The cytochemical parameters returned to the normal within 24 hours. The decline in the activity of cytochrome oxidase, peroxidase and in the lipid content of peripheral neutrophils was followed by a decrease in the phagocytic activity. These changes were closely correlated.", "contents": "[Action of oxygen under increased pressure on the neutrophil metabolism in the peripheral blood]. The effect of hyperbaric oxygen (1--5 ata for 1 hr) on the activity of cytochrome oxidase, peroxidase, lipid content and phagocytic activity of neutrophils was studied. The dynamics of the recovery of those parameters was followed. A multimodal relationship between the pressure level and changes in the enzyme activity and lipid content was noted. The decrease in the activity of peroxidase was more pronounced than that of cytochrome oxidase in all cases. The dynamics of the recovery of the above parameters was shown to depend on the pressure level. The cytochemical parameters returned to the normal within 24 hours. The decline in the activity of cytochrome oxidase, peroxidase and in the lipid content of peripheral neutrophils was followed by a decrease in the phagocytic activity. These changes were closely correlated."}
{"id": "PMID:221739", "title": "Sequential analysis of hepatic carcinogenesis: a comparative study of the ultrastructure of preneoplastic, malignant, prenatal, postnatal, and regenerating liver.", "content": "The objective of this study was to compare the fine structure of presumptive preneoplastic hepatocytes at various times during liver carcinogenesis with that of normal, developing, and regenerating liver and of hepatocellular carcinomas, using transmission and scanning electron microscopy. A new model of liver carcinogenesis was used in which several of the early steps are quite well synchronized. A single initiating dose of diethylnitrosamine induced isolated islands of altered hepatocytes. The cells were characterized by persistence of glycogen despite starvation, increase in smooth endoplasmic reticulum, and hypertrophic nucleoli. Following intense selection of the altered hepatocytes by dietary 2-acetylaminofluorene plus partial hepatectomy, the affected hepatocytes proliferated rapidly to produce basophilic foci. These early hyperplastic lesions revealed stellate-shaped dilated bile canaliculi lined by blebs and abnormally thick elongated microvilli, a decreased number of microvilli on the sinusoidal surface, a marked increase in smooth endoplasmic reticulum, large nucleoli, and bundles of pericanalicular microfilaments. A majority of the proliferating lesions reacquired a normal organizational pattern within several weeks after partial hepatectomy and could not be distinguished from normal liver. A small number continued to grow and become typical persistent hyperplastic nodules. These showed significant widening of intercellular spaces between hepatocytes, elongated microvilli over large regions of the cell surface, many invaginations of the cell membrane, and irregularly shaped bile canaliculi. Sequential changes in focal hyperplastic hepatocytes during carcinogenesis could be distinguished from normal, developing, and regenerating liver. The major differences involved the cell surfaces and cytoplasmic organelles. The findings are compatible with the hypothesis that a carcinogen may act by inducing alterations in a small number of hepatocytes and that hepatocellular carcinomas arise through stepwise evolutional changes in these cells.", "contents": "Sequential analysis of hepatic carcinogenesis: a comparative study of the ultrastructure of preneoplastic, malignant, prenatal, postnatal, and regenerating liver. The objective of this study was to compare the fine structure of presumptive preneoplastic hepatocytes at various times during liver carcinogenesis with that of normal, developing, and regenerating liver and of hepatocellular carcinomas, using transmission and scanning electron microscopy. A new model of liver carcinogenesis was used in which several of the early steps are quite well synchronized. A single initiating dose of diethylnitrosamine induced isolated islands of altered hepatocytes. The cells were characterized by persistence of glycogen despite starvation, increase in smooth endoplasmic reticulum, and hypertrophic nucleoli. Following intense selection of the altered hepatocytes by dietary 2-acetylaminofluorene plus partial hepatectomy, the affected hepatocytes proliferated rapidly to produce basophilic foci. These early hyperplastic lesions revealed stellate-shaped dilated bile canaliculi lined by blebs and abnormally thick elongated microvilli, a decreased number of microvilli on the sinusoidal surface, a marked increase in smooth endoplasmic reticulum, large nucleoli, and bundles of pericanalicular microfilaments. A majority of the proliferating lesions reacquired a normal organizational pattern within several weeks after partial hepatectomy and could not be distinguished from normal liver. A small number continued to grow and become typical persistent hyperplastic nodules. These showed significant widening of intercellular spaces between hepatocytes, elongated microvilli over large regions of the cell surface, many invaginations of the cell membrane, and irregularly shaped bile canaliculi. Sequential changes in focal hyperplastic hepatocytes during carcinogenesis could be distinguished from normal, developing, and regenerating liver. The major differences involved the cell surfaces and cytoplasmic organelles. The findings are compatible with the hypothesis that a carcinogen may act by inducing alterations in a small number of hepatocytes and that hepatocellular carcinomas arise through stepwise evolutional changes in these cells."}
{"id": "PMID:221740", "title": "Migration of human vascular endothelial and smooth muscle cells.", "content": "Migration of endothelial and smooth muscle cells was studied in vitro by measuring the increase in surface area at specific time intervals of confluent cell colonies advancing under agarose gels that contained both Morgan's medium 199 and variuos types of sera. First passage cultures of endothelial cells or 3 to 6 passage smooth muscle cells were plated into wells punched in agarose gels, at a seeding density of 50,000 cells per well. At zero time the size of the cell colonies was 35.4 sq. mm. +/- standard error 0.1. Irradiation (1500 rads) did not affect the expansion of the cell colonies although 3H-thymidine uptake was inhibited. Endothelial cells migrated under the agarose gels concentrically as contiguous sheets. When exposed to either 20 per cent platelet-poor plasma serum, platelet-rich plasma serum, or whole blood serum, the average increase in surface area was approximately 9 sq. mm. per day. In contrast, arterial smooth muscle cell colonies expanded with an increment of approximately 9 sq. mm. per day when exposed to 10 per cent platelet-poor plasma serum but 12 sq. mm. per day when exposed to 10 per cent platelet-rich plasma serum (p less than 0.001). Platelet factors also had stimulatory effects on the migration of venous smooth muscle cells. Cytochalasin B, dibutyryl cyclic AMP, and theophylline inhibited the migration of both endothelial and smooth muscle cells, but the latter responded more to the inhibitory effects of all three agents. It is concluded that in contrast to vascular smooth muscle, endothelial cells do not require platelet factors for migration and are less responsive to specific inhibitors affecting cell movement.", "contents": "Migration of human vascular endothelial and smooth muscle cells. Migration of endothelial and smooth muscle cells was studied in vitro by measuring the increase in surface area at specific time intervals of confluent cell colonies advancing under agarose gels that contained both Morgan's medium 199 and variuos types of sera. First passage cultures of endothelial cells or 3 to 6 passage smooth muscle cells were plated into wells punched in agarose gels, at a seeding density of 50,000 cells per well. At zero time the size of the cell colonies was 35.4 sq. mm. +/- standard error 0.1. Irradiation (1500 rads) did not affect the expansion of the cell colonies although 3H-thymidine uptake was inhibited. Endothelial cells migrated under the agarose gels concentrically as contiguous sheets. When exposed to either 20 per cent platelet-poor plasma serum, platelet-rich plasma serum, or whole blood serum, the average increase in surface area was approximately 9 sq. mm. per day. In contrast, arterial smooth muscle cell colonies expanded with an increment of approximately 9 sq. mm. per day when exposed to 10 per cent platelet-poor plasma serum but 12 sq. mm. per day when exposed to 10 per cent platelet-rich plasma serum (p less than 0.001). Platelet factors also had stimulatory effects on the migration of venous smooth muscle cells. Cytochalasin B, dibutyryl cyclic AMP, and theophylline inhibited the migration of both endothelial and smooth muscle cells, but the latter responded more to the inhibitory effects of all three agents. It is concluded that in contrast to vascular smooth muscle, endothelial cells do not require platelet factors for migration and are less responsive to specific inhibitors affecting cell movement."}
{"id": "PMID:221741", "title": "Electron and immunoelectron microscopic study on liver tissues of marmosets infected with hepatitis A virus.", "content": "Electron and immunoelectron microscopic studies were carried out on liver tissues from three marmosets, experimentally infected with hepatitis A virus and sacrificed during the acute phase of illness. Ultrastructurally, the liver cells demonstrated marked cisternal dilation of endoplasmic reticulum and vesicular transformation and contortion of endoplasmic reticulum profiles. Clusters of virus-like particles of 24 to 27 nm. in diameter, both \"solid\" and \"empty\" forms, were found in membrane-bound cytoplasmic vesicles. In one animal, the virus-like particles were significantly smaller, measuring 17 to 22 nm. in size, and almost all were solid forms embedded in an amorphous matrix. Clusters of virus-like particles were found in the bile canaliculi of liver cell cords and in lysosomal structures of monocytes or Kupffer cells in the hepatic sinusoids. The latter correlated with the immunofluorescent microscopic finding. Indirect immunoferritin staining was carried out on fresh and formalin-fixed liver tissues, using convalescent phase serum from patients recovered from hepatitis A virus infection as the primary antibody, and the ferritin-labeled rabbit anti-human IgG or ferritin-labeled staphylococcal protein A as the secondary antibody. Specific stainings were observed with the virus-like particles, indicating that the particles were probably antigenically related to hepatitis A virus. Our findings are in agreement with the immunofluorescent and immunoelectron microscopic studies reported by others and support the concept that hepatitis A virus is produced in the liver. The infection seems to produce cytopathic effect especially to the endoplasmic reticulum organelle of hepatocytes.", "contents": "Electron and immunoelectron microscopic study on liver tissues of marmosets infected with hepatitis A virus. Electron and immunoelectron microscopic studies were carried out on liver tissues from three marmosets, experimentally infected with hepatitis A virus and sacrificed during the acute phase of illness. Ultrastructurally, the liver cells demonstrated marked cisternal dilation of endoplasmic reticulum and vesicular transformation and contortion of endoplasmic reticulum profiles. Clusters of virus-like particles of 24 to 27 nm. in diameter, both \"solid\" and \"empty\" forms, were found in membrane-bound cytoplasmic vesicles. In one animal, the virus-like particles were significantly smaller, measuring 17 to 22 nm. in size, and almost all were solid forms embedded in an amorphous matrix. Clusters of virus-like particles were found in the bile canaliculi of liver cell cords and in lysosomal structures of monocytes or Kupffer cells in the hepatic sinusoids. The latter correlated with the immunofluorescent microscopic finding. Indirect immunoferritin staining was carried out on fresh and formalin-fixed liver tissues, using convalescent phase serum from patients recovered from hepatitis A virus infection as the primary antibody, and the ferritin-labeled rabbit anti-human IgG or ferritin-labeled staphylococcal protein A as the secondary antibody. Specific stainings were observed with the virus-like particles, indicating that the particles were probably antigenically related to hepatitis A virus. Our findings are in agreement with the immunofluorescent and immunoelectron microscopic studies reported by others and support the concept that hepatitis A virus is produced in the liver. The infection seems to produce cytopathic effect especially to the endoplasmic reticulum organelle of hepatocytes."}
{"id": "PMID:221748", "title": "Classification of men arrested for driving while intoxicated, and treatment implications. A cluster-analytic study.", "content": "Statistical analysis of blood alcohol concentration at time of arrest, quantity-frequency level of drinking and scores on an impairment index and the N Scale of the Eysenck Personality Inventory differentiated 7 types among 1500 men arrested for driving while intoxicated.", "contents": "Classification of men arrested for driving while intoxicated, and treatment implications. A cluster-analytic study. Statistical analysis of blood alcohol concentration at time of arrest, quantity-frequency level of drinking and scores on an impairment index and the N Scale of the Eysenck Personality Inventory differentiated 7 types among 1500 men arrested for driving while intoxicated."}
{"id": "PMID:221749", "title": "Alcoholics Anonymous as treatment and as ideology.", "content": "It is proposed that Alcoholics Anonymous's continued domination of the alcoholism treatment field has fettered innovation, precluded early intervention and limited treatment strategies.", "contents": "Alcoholics Anonymous as treatment and as ideology. It is proposed that Alcoholics Anonymous's continued domination of the alcoholism treatment field has fettered innovation, precluded early intervention and limited treatment strategies."}
{"id": "PMID:221750", "title": "Steroid receptors in sarcomatous lesions.", "content": "Clinical observations showed that the natural history of sarcomatous lesions may be different among males and females, and it may be influenced by hormonal factors. Estrogen receptors (ER) were measured on biopsy specimens of melanoma (two patients), soft-tissue sarcoma (four patients), cystosarcoma phylloides (five patients), benign breast tissues (27 patients), and breast carcinoma (109 patients). Thirty-four specimens also had progesterone receptors (PR) analyzed. One of the five cystosarcoma phylloides and five of the six nonmammary sarcoma tissues contained ER (mainly of the 4 Svedburg (S) variety) of more than 7 femtomoles (fmoles)/mg cytosol proteins (6/11 = 54%). For comparison three of the 14 fibroadenoma specimens and two of the 13 patients with other benign lesions had positive ERs (5/27 = 19%), whereas 56% of the breast carcinomas were ER positive. Since the amount of 8S ER found in sarcomatous tissues is relatively low, hormonal treatment would not be effective.", "contents": "Steroid receptors in sarcomatous lesions. Clinical observations showed that the natural history of sarcomatous lesions may be different among males and females, and it may be influenced by hormonal factors. Estrogen receptors (ER) were measured on biopsy specimens of melanoma (two patients), soft-tissue sarcoma (four patients), cystosarcoma phylloides (five patients), benign breast tissues (27 patients), and breast carcinoma (109 patients). Thirty-four specimens also had progesterone receptors (PR) analyzed. One of the five cystosarcoma phylloides and five of the six nonmammary sarcoma tissues contained ER (mainly of the 4 Svedburg (S) variety) of more than 7 femtomoles (fmoles)/mg cytosol proteins (6/11 = 54%). For comparison three of the 14 fibroadenoma specimens and two of the 13 patients with other benign lesions had positive ERs (5/27 = 19%), whereas 56% of the breast carcinomas were ER positive. Since the amount of 8S ER found in sarcomatous tissues is relatively low, hormonal treatment would not be effective."}
{"id": "PMID:221752", "title": "Preoperative and postoperative technetium-99m pyrophosphate myocardial scintigraphy in the assessment of operative infarction in coronary artery surgery.", "content": "The incidence of operative myocardial infarction was assessed by electrocardiogram (ECG) and technetium-99m pyrophosphate (99mTc-PyP) myocardial scintigrams in 89 consecutive patients undergoing coronary artery bypass grafting (CABG). Myocardial scintigrams were performed on the day before operation and repeated 2 to 3 days postoperatively. All patients survived operation, with three in-hospital deaths not related to myocardial infarction (mortality rate 3 percent). Operative infarction was assessed to have occurred in four of 89 patients (4 percent). Two had new Q waves and positive scintigrams; one, major ST-T wave changes and a positive scintigram; and the fourth, new Q waves without a positive scintigram. Three further patients (3 percent) had Q waves and positive scintigrams postoperatively, but myocardial infarction was evolving before anesthesia and operation. Twenty-seven of 89 patients (30 percent) were found to have abnormal scintigrams preoperatively. In two patients, both operated upon with evolving myocardial infarction, the scintigram was worse postoperatively. In 13 patients the scintigram was improved after operation. In 12 patients (13 percent) the abnormal preoperative scintigram was unchanged after operation. Preoperative and postoperative myocardial scintigrams and ECG's must be compared to assess the incidence of operative myocardial infarction in patients undergoing CABG.", "contents": "Preoperative and postoperative technetium-99m pyrophosphate myocardial scintigraphy in the assessment of operative infarction in coronary artery surgery. The incidence of operative myocardial infarction was assessed by electrocardiogram (ECG) and technetium-99m pyrophosphate (99mTc-PyP) myocardial scintigrams in 89 consecutive patients undergoing coronary artery bypass grafting (CABG). Myocardial scintigrams were performed on the day before operation and repeated 2 to 3 days postoperatively. All patients survived operation, with three in-hospital deaths not related to myocardial infarction (mortality rate 3 percent). Operative infarction was assessed to have occurred in four of 89 patients (4 percent). Two had new Q waves and positive scintigrams; one, major ST-T wave changes and a positive scintigram; and the fourth, new Q waves without a positive scintigram. Three further patients (3 percent) had Q waves and positive scintigrams postoperatively, but myocardial infarction was evolving before anesthesia and operation. Twenty-seven of 89 patients (30 percent) were found to have abnormal scintigrams preoperatively. In two patients, both operated upon with evolving myocardial infarction, the scintigram was worse postoperatively. In 13 patients the scintigram was improved after operation. In 12 patients (13 percent) the abnormal preoperative scintigram was unchanged after operation. Preoperative and postoperative myocardial scintigrams and ECG's must be compared to assess the incidence of operative myocardial infarction in patients undergoing CABG."}
{"id": "PMID:221753", "title": "A search for antibodies to luteinizing hormone receptors in premature ovarian failure.", "content": "We recently published evidence of the presence of circulating antibodies in the sera of patients who had the diagnosis of premature menopause syndrome. This led to the question: Is there a circulating antibody in the sera of patients with premature menopause syndrome which interferes with gonadotropin-luteinizing hormone (LH) receptor interaction on the luteal cell surface? Serum samples from 14 women with the diagnosis of Premature menopause syndrome were examined to see whether they would block the binding of 125I-labeled human chorionic gonadotropin (hCG) to human corpora lutea. All patients had spontaneous cessation of menses before the age of 35 years and documentation of increased gonadotropin secretion and failure of estrogen secretion. When the sera of the study group were incubated with 125I-labeled hCG and LH receptor from human corpora lutea, no difference in binding was observed when compared with controls. This suggests that there is no circulating antibody that interferes with hCG-LH receptor interaction and that would thereby lead to loss of ovarian function in premature menopause syndrome.", "contents": "A search for antibodies to luteinizing hormone receptors in premature ovarian failure. We recently published evidence of the presence of circulating antibodies in the sera of patients who had the diagnosis of premature menopause syndrome. This led to the question: Is there a circulating antibody in the sera of patients with premature menopause syndrome which interferes with gonadotropin-luteinizing hormone (LH) receptor interaction on the luteal cell surface? Serum samples from 14 women with the diagnosis of Premature menopause syndrome were examined to see whether they would block the binding of 125I-labeled human chorionic gonadotropin (hCG) to human corpora lutea. All patients had spontaneous cessation of menses before the age of 35 years and documentation of increased gonadotropin secretion and failure of estrogen secretion. When the sera of the study group were incubated with 125I-labeled hCG and LH receptor from human corpora lutea, no difference in binding was observed when compared with controls. This suggests that there is no circulating antibody that interferes with hCG-LH receptor interaction and that would thereby lead to loss of ovarian function in premature menopause syndrome."}
{"id": "PMID:221755", "title": "Classification of pancreatic cancer (nonendocrine).", "content": "From the records of 757 patients listed as having had pancreatic cancer at Memorial Hospital during the years 1949 through 1972, adequate clinical data and pathologic tissue were available for study in 508 patients. Review of these cases led to a histologic classification into 11 subcategories and one unclassified group. The most common type was the duct cell adenocarcinoma (75%), and the remaining subgroups each made up less than 5% of the total. All except one of the subtypes were well-known carcinoma patterns that occur in other organs. A small-gland carcinoma, the microadenocarcinoma, has not usually been associated with the pancreas. Some types were associated with short survival periods of a few months after diagnosis--for example, duct cell, giant cell, acinar cell, and adenosquamous carcinomas and microadenocarcinoma. Patients with mucinous carcinoma had a mean survival period of a few months longer, and the few patients with mucinous cystadenocarcinoma had a much longer median survival. Two rare types--papillary cystic tumor and pancreaticoblastoma--are mentioned and illustrated. It is hoped that one or more of these types can be associated with an etiologic agent, some clinical feature, or responsiveness to a therapeutic regimen.", "contents": "Classification of pancreatic cancer (nonendocrine). From the records of 757 patients listed as having had pancreatic cancer at Memorial Hospital during the years 1949 through 1972, adequate clinical data and pathologic tissue were available for study in 508 patients. Review of these cases led to a histologic classification into 11 subcategories and one unclassified group. The most common type was the duct cell adenocarcinoma (75%), and the remaining subgroups each made up less than 5% of the total. All except one of the subtypes were well-known carcinoma patterns that occur in other organs. A small-gland carcinoma, the microadenocarcinoma, has not usually been associated with the pancreas. Some types were associated with short survival periods of a few months after diagnosis--for example, duct cell, giant cell, acinar cell, and adenosquamous carcinomas and microadenocarcinoma. Patients with mucinous carcinoma had a mean survival period of a few months longer, and the few patients with mucinous cystadenocarcinoma had a much longer median survival. Two rare types--papillary cystic tumor and pancreaticoblastoma--are mentioned and illustrated. It is hoped that one or more of these types can be associated with an etiologic agent, some clinical feature, or responsiveness to a therapeutic regimen."}
{"id": "PMID:221756", "title": "Age-dependent physiochemical and biochemical studies of human red cell membranes.", "content": "Erythrocyte ghosts of male persons of two age groups, younger than thirty and older than seventy years, were analyzed to investigate the imfluence of age on lipid composition, the physical state of the lipid phase, Na+K+-ATPase activity and sialic acid content. The phospholipid content in red cell membranes of old donors is significantly lower than in young ones. Cholesterol and fatty acid compositions shows no difference between the two donor groups. The membrane fluidity in liposomes prepared from total lipids of old donor decreased. No significant difference in lipid composition and membrane fluidity reflected by the spin labels was observed between blood group A and O. The activity of Na+K+-ATPase of the young donors with blood group A is significantly higher than those of old donors. The results also demonstrate a decrease of sialic acid content of red cells of old donors.", "contents": "Age-dependent physiochemical and biochemical studies of human red cell membranes. Erythrocyte ghosts of male persons of two age groups, younger than thirty and older than seventy years, were analyzed to investigate the imfluence of age on lipid composition, the physical state of the lipid phase, Na+K+-ATPase activity and sialic acid content. The phospholipid content in red cell membranes of old donors is significantly lower than in young ones. Cholesterol and fatty acid compositions shows no difference between the two donor groups. The membrane fluidity in liposomes prepared from total lipids of old donor decreased. No significant difference in lipid composition and membrane fluidity reflected by the spin labels was observed between blood group A and O. The activity of Na+K+-ATPase of the young donors with blood group A is significantly higher than those of old donors. The results also demonstrate a decrease of sialic acid content of red cells of old donors."}
{"id": "PMID:221757", "title": "Changes in intracellular activities of lysosomal enzymes in tissues of rats during aging.", "content": "A comparison of results obtained from studies of the intracellular fractions of the tissues of liver, brain and heart of \"young\" (1-2 months), \"old\" (24-27 months) and \"senile\" (34-37 months) rats showed that the ratios of three enzymes, acid phosphatase, beta-N-acetylglucosaminidase and acid RNase of the liver and heart were very similar and their activities decreased with age. On the other hand, the protein content is the supernatant of the liver, and acid DNase activities in the supernatant of the brain increased significantly with age. When the 24-27 month and 34-37 month old rats were compared, the ratios of the total activities of liver beta-N-glucosaminidase and brain acid DNase in the supernatant and the specific activities of brain beta-N-glucosaminidase in the microsomal fraction increased significantly.", "contents": "Changes in intracellular activities of lysosomal enzymes in tissues of rats during aging. A comparison of results obtained from studies of the intracellular fractions of the tissues of liver, brain and heart of \"young\" (1-2 months), \"old\" (24-27 months) and \"senile\" (34-37 months) rats showed that the ratios of three enzymes, acid phosphatase, beta-N-acetylglucosaminidase and acid RNase of the liver and heart were very similar and their activities decreased with age. On the other hand, the protein content is the supernatant of the liver, and acid DNase activities in the supernatant of the brain increased significantly with age. When the 24-27 month and 34-37 month old rats were compared, the ratios of the total activities of liver beta-N-glucosaminidase and brain acid DNase in the supernatant and the specific activities of brain beta-N-glucosaminidase in the microsomal fraction increased significantly."}
{"id": "PMID:221758", "title": "Effect of sera from hyperlipidemic subjects and high-density lipoproteinemic runners on the synthesis of DNA and glycosaminoglycans by cultured human aortic smooth muscle cells.", "content": "Effects of hyperlipidemic, normolipidemic and high-density-lipoproteinemic (HD lipoproteinemic) sera from active runners were studied on cultured human aortic smooth muscle cells. The synthesis of DNA, hyaluronic acid and sulphated glycosaminoglycans (GAGs) in the presence of the various sera was measured by the incorporation of [3H]-thymidine and [3H]-glucosamine. The HD lipoproteinemic sera from runners stimulated the synthesis of DNA and sulphated GAGs less than normolipidemic and hyperlipidemic sera. The hyperlipidemic sera stimulated the synthesis of DNA slightly more than the other sera, but only after a 24 h preincubation. Accordingly, the concentration of HDL-cholesterol in serum was negatively correlated with the synthesis of DNA (r = -0.77, P less than 0.01) and sulphated glycosaminoglycans (r = -0.81, P less than 0.01). The sulphated GAGs/hyaluronate ratio was smaller in the presence of HD lipoproteinemic serum as compared with the other sera. The proliferation of aortic smooth muscle cells and the rate at which they synthesize sulphated GAGs have been considered important during the initiation of atherosclerosis in vivo. The present results suggest that sera having differences in the relative amounts of various lipoprotein fractions differ significantly in their influence on both of these arterial smooth muscle cell functions in vitro.", "contents": "Effect of sera from hyperlipidemic subjects and high-density lipoproteinemic runners on the synthesis of DNA and glycosaminoglycans by cultured human aortic smooth muscle cells. Effects of hyperlipidemic, normolipidemic and high-density-lipoproteinemic (HD lipoproteinemic) sera from active runners were studied on cultured human aortic smooth muscle cells. The synthesis of DNA, hyaluronic acid and sulphated glycosaminoglycans (GAGs) in the presence of the various sera was measured by the incorporation of [3H]-thymidine and [3H]-glucosamine. The HD lipoproteinemic sera from runners stimulated the synthesis of DNA and sulphated GAGs less than normolipidemic and hyperlipidemic sera. The hyperlipidemic sera stimulated the synthesis of DNA slightly more than the other sera, but only after a 24 h preincubation. Accordingly, the concentration of HDL-cholesterol in serum was negatively correlated with the synthesis of DNA (r = -0.77, P less than 0.01) and sulphated glycosaminoglycans (r = -0.81, P less than 0.01). The sulphated GAGs/hyaluronate ratio was smaller in the presence of HD lipoproteinemic serum as compared with the other sera. The proliferation of aortic smooth muscle cells and the rate at which they synthesize sulphated GAGs have been considered important during the initiation of atherosclerosis in vivo. The present results suggest that sera having differences in the relative amounts of various lipoprotein fractions differ significantly in their influence on both of these arterial smooth muscle cell functions in vitro."}
{"id": "PMID:221759", "title": "Psychosocial determinants of immunization behavior in a swine influenza campaign.", "content": "A prospective design was used to study factors which predisposed individuals to receive vaccination in response to the anticipated outbreak of swine influenza in the fall and winter of 1976. Data were obtained from a telephone survey of 286 adults in Oakland County, Michigan. Predictor variables included Health Belief Model (HBM) variables as well as measures of behavioral intention, social influence, physician's advice, socioeconomic status and past experience with flu shots. In multivariate analysis, over 40 per cent of the variance in inoculation behavior was explained by the predictors used. Path analysis revealed that most of the HBM variables' influence on behavior was mediated through behavioral intention. While behavioral intention was an important predictor of inoculation behavior, other psychosocial factors played a significant role in explaining variance in the dependent variable.", "contents": "Psychosocial determinants of immunization behavior in a swine influenza campaign. A prospective design was used to study factors which predisposed individuals to receive vaccination in response to the anticipated outbreak of swine influenza in the fall and winter of 1976. Data were obtained from a telephone survey of 286 adults in Oakland County, Michigan. Predictor variables included Health Belief Model (HBM) variables as well as measures of behavioral intention, social influence, physician's advice, socioeconomic status and past experience with flu shots. In multivariate analysis, over 40 per cent of the variance in inoculation behavior was explained by the predictors used. Path analysis revealed that most of the HBM variables' influence on behavior was mediated through behavioral intention. While behavioral intention was an important predictor of inoculation behavior, other psychosocial factors played a significant role in explaining variance in the dependent variable."}
{"id": "PMID:221760", "title": "Drug-induced chronic hepatic disease.", "content": "A number of chronic hepatic lesions can result from adverse reactions to medicinal agents. Such lesions include a form of chronic active hepatitis; hepatic steatosis, phoepholipidosis and granulomatosis; several vascular lesions; two types of noncirrhotic portal hypertension; several types of cirrhosis and several neoplasms.", "contents": "Drug-induced chronic hepatic disease. A number of chronic hepatic lesions can result from adverse reactions to medicinal agents. Such lesions include a form of chronic active hepatitis; hepatic steatosis, phoepholipidosis and granulomatosis; several vascular lesions; two types of noncirrhotic portal hypertension; several types of cirrhosis and several neoplasms."}
{"id": "PMID:221762", "title": "Evaluation of otic drops on infection and healing of traumatic tympanic membrane perforations.", "content": "Guinea pigs were used to compare the efficacy of three commercially available otic preparations in treating traumatic tympanic membrane perforations. The results suggest that a clear, viscous solution of low pH will significantly reduce the incidence of infection and will not retard subsequent membrane healing.", "contents": "Evaluation of otic drops on infection and healing of traumatic tympanic membrane perforations. Guinea pigs were used to compare the efficacy of three commercially available otic preparations in treating traumatic tympanic membrane perforations. The results suggest that a clear, viscous solution of low pH will significantly reduce the incidence of infection and will not retard subsequent membrane healing."}
{"id": "PMID:221763", "title": "Cerebrospinal fluid rhinorrhea.", "content": "One hundred and nine cases of cerebrospinal fluid rhinorrhea occurring over a ten-year period are reviewed. Experience with the use of fluorescein localization techniques in 45 cases is detailed. The simplicity, easy availability and safety of fluorescein techniques are stressed. Primary rhinologic repair is advocated.", "contents": "Cerebrospinal fluid rhinorrhea. One hundred and nine cases of cerebrospinal fluid rhinorrhea occurring over a ten-year period are reviewed. Experience with the use of fluorescein localization techniques in 45 cases is detailed. The simplicity, easy availability and safety of fluorescein techniques are stressed. Primary rhinologic repair is advocated."}
{"id": "PMID:221772", "title": "Substrate selectivity of diacylglycerol kinase in guinea pig brain.", "content": "The present study was conducted to test the selectivity of the microsomal diaclyglycerol kinase (ATP:1,2-diacyl-sn-glycerol-phosphotransferase) from guinea pig brain towards different, 1,2-diacyl-sn-glycerols. The molecular species added to the incubation medium as substrates were a mixture of the 1-[3H]palmitoyl plus 1-[14C]stearoyl homologs of either the monoenoic (2-oleoyl), dienoic (2-linoleoyl), tetraenoic (2-arachidonoyl), or hexaenoic (2-docosahexaenoyl) diacylglycerols. Rates of phosphatidic acid synthesis (1-palmitoy plus 1-stearoyl homologs) with each of the four classes of unsaturated diacylglycerols were not greatly different, although they were moderately higher in the case of the monoenes. No marked enzyme selectivity for either the 1-palmitoyl or 1-stearoyl homolog of the various 1-saturated 2-unsaturated diacylglycerols was apparent. Generally similar results were obtained with the diacylglycerol kinase in rat brain microsomes.", "contents": "Substrate selectivity of diacylglycerol kinase in guinea pig brain. The present study was conducted to test the selectivity of the microsomal diaclyglycerol kinase (ATP:1,2-diacyl-sn-glycerol-phosphotransferase) from guinea pig brain towards different, 1,2-diacyl-sn-glycerols. The molecular species added to the incubation medium as substrates were a mixture of the 1-[3H]palmitoyl plus 1-[14C]stearoyl homologs of either the monoenoic (2-oleoyl), dienoic (2-linoleoyl), tetraenoic (2-arachidonoyl), or hexaenoic (2-docosahexaenoyl) diacylglycerols. Rates of phosphatidic acid synthesis (1-palmitoy plus 1-stearoyl homologs) with each of the four classes of unsaturated diacylglycerols were not greatly different, although they were moderately higher in the case of the monoenes. No marked enzyme selectivity for either the 1-palmitoyl or 1-stearoyl homolog of the various 1-saturated 2-unsaturated diacylglycerols was apparent. Generally similar results were obtained with the diacylglycerol kinase in rat brain microsomes."}
{"id": "PMID:221779", "title": "[Effect of vibration and noise on various morphotic elements in the peripheral blood of exposed workers].", "content": "The authors examined blood cell count in 198 males and 53 females occupationally exposed to vibration and noise surpassing allowable standards. In addition, in some subjects cytochemical examinations of leukocytes were performed. Decreased amounts of erythrocytes and hemoglobin content were found. Cytochemical examinations showed an increased activity of non-specific esterase, increase PAS reaction, decreased activity of acid phosphatase, and the tendency to decrease the activity of base phosphatase.", "contents": "[Effect of vibration and noise on various morphotic elements in the peripheral blood of exposed workers]. The authors examined blood cell count in 198 males and 53 females occupationally exposed to vibration and noise surpassing allowable standards. In addition, in some subjects cytochemical examinations of leukocytes were performed. Decreased amounts of erythrocytes and hemoglobin content were found. Cytochemical examinations showed an increased activity of non-specific esterase, increase PAS reaction, decreased activity of acid phosphatase, and the tendency to decrease the activity of base phosphatase."}
{"id": "PMID:221781", "title": "Effect of diabetes and fasting on the uridine triphosphate content and uridine kinase activity of rat cardiac and skeletal muscle.", "content": "The influence of diabetes and starvation on uracil nucleotide metabolism in muscle was studied. It was found that the uridine triphosphate (UTP) content of heart and diaphragm muscle was decreased in fasted and streptozotocin-diabetic rats and that insulin treatment of diabetic animals restored the UTP concentration to normal levels. The ATP content of heart tissue was not altered under these conditions. It was also demonstrated that hemidiaphragms from streptozotocin-diabetic rats synthesized less UTP from uridine in vitro than hemidiaphragms from normal animals. Uridine kinase activity of extracts of cardiac and skeletal muscle from fasted and diabetic rats was lower than the activity found in extracts from control animals. It was concluded that uracil nucleotide synthesis by the salvage pathway is decreased in experimental diabetes and fasting.", "contents": "Effect of diabetes and fasting on the uridine triphosphate content and uridine kinase activity of rat cardiac and skeletal muscle. The influence of diabetes and starvation on uracil nucleotide metabolism in muscle was studied. It was found that the uridine triphosphate (UTP) content of heart and diaphragm muscle was decreased in fasted and streptozotocin-diabetic rats and that insulin treatment of diabetic animals restored the UTP concentration to normal levels. The ATP content of heart tissue was not altered under these conditions. It was also demonstrated that hemidiaphragms from streptozotocin-diabetic rats synthesized less UTP from uridine in vitro than hemidiaphragms from normal animals. Uridine kinase activity of extracts of cardiac and skeletal muscle from fasted and diabetic rats was lower than the activity found in extracts from control animals. It was concluded that uracil nucleotide synthesis by the salvage pathway is decreased in experimental diabetes and fasting."}
{"id": "PMID:221782", "title": "Sucrose-induced changes in VLDL- and LDL-B apoprotein removal rates.", "content": "Dietary sucrose has been shown to increase triglyceride transport in very-low-density lipoproteins (VLDL), but it is not known whether the metabolism of the entire particle is affected. Measurements were therefore carried out on VLDL-B apoprotein flux and removal rate before and after the consumption of high sucrose diets (55% of calories). Autologous 125I-labeled VLDL were injected and the specific activity-time curves analyzed by two-pool kinetics. Two kinds of response to sucrose were seen. In two subjects, the pool of VLDL-B apoprotein decreased by 20% and 14% (despite increased fluxes) due to substantial increases in removal rates of 42% and 116%. In four subjects, pool size expanded by 154%, 426%, 50% and 105%, primarily as the result of decreased removal rates (decreases of 55%, 67%, 30%, and 43%). Changes in flux were inconstant, suggesting that accumulation of VLDL particles was related to delayed clearance rather than to increased formation. This may reflect the longer time required to remove the larger load of triglyceride from each particle. The catabolic rate of low-density lipoprotein (LDL) was also measured in five subjects: in four, the clearance of LDL increased with sucrose and was associated with decreases in LDL-B apoprotein and plasma cholesterol.", "contents": "Sucrose-induced changes in VLDL- and LDL-B apoprotein removal rates. Dietary sucrose has been shown to increase triglyceride transport in very-low-density lipoproteins (VLDL), but it is not known whether the metabolism of the entire particle is affected. Measurements were therefore carried out on VLDL-B apoprotein flux and removal rate before and after the consumption of high sucrose diets (55% of calories). Autologous 125I-labeled VLDL were injected and the specific activity-time curves analyzed by two-pool kinetics. Two kinds of response to sucrose were seen. In two subjects, the pool of VLDL-B apoprotein decreased by 20% and 14% (despite increased fluxes) due to substantial increases in removal rates of 42% and 116%. In four subjects, pool size expanded by 154%, 426%, 50% and 105%, primarily as the result of decreased removal rates (decreases of 55%, 67%, 30%, and 43%). Changes in flux were inconstant, suggesting that accumulation of VLDL particles was related to delayed clearance rather than to increased formation. This may reflect the longer time required to remove the larger load of triglyceride from each particle. The catabolic rate of low-density lipoprotein (LDL) was also measured in five subjects: in four, the clearance of LDL increased with sucrose and was associated with decreases in LDL-B apoprotein and plasma cholesterol."}
{"id": "PMID:221783", "title": "Reduction of plasma triglyceride concentration by acute stress in man.", "content": "Three different forms of stress all resulted in acute reduction of plasma triglyceride concentrations. Pyrogen reactions in two hypertriglyceridemic men resulted in the lowering of very-low-density lipoprotein (VLDL) triglyceride levels by 93% and 73% due to decreased secretion of this lipoprotein into plasma. More modest reductions in plasma triglycerides were observed after 2-deoxyglucose-induced intracellular glucopenia and insulin-induced hypoglycemia. With hypoglycemia, the lowering of plasma triglyceride concentration correlated significantly with the stimulation of urinary epinephrine output (r = 0.86) but with neither the urinary norepinephrine response nor with the increase in plasma immunoreactive glucagon levels. To further test whether these changes in plasma triglyceride levels were mediated via the sympathetic nervous system, hypoglycemia was evoked by insulin in subjects with traumatic spinal cord transactions. Two such subjects, who demonstrated sympathetic stimulation in response to hypoglycemia, had evidence of reduced VLDL secretion into plasma, while in two who had no evidence of an adrenergic response. VLDL secretion was not inhibited. Thus, acute lowering of plasma triglyceride concentrations by certain forms of stress appears to be mediated via the sympathetic nervous system.", "contents": "Reduction of plasma triglyceride concentration by acute stress in man. Three different forms of stress all resulted in acute reduction of plasma triglyceride concentrations. Pyrogen reactions in two hypertriglyceridemic men resulted in the lowering of very-low-density lipoprotein (VLDL) triglyceride levels by 93% and 73% due to decreased secretion of this lipoprotein into plasma. More modest reductions in plasma triglycerides were observed after 2-deoxyglucose-induced intracellular glucopenia and insulin-induced hypoglycemia. With hypoglycemia, the lowering of plasma triglyceride concentration correlated significantly with the stimulation of urinary epinephrine output (r = 0.86) but with neither the urinary norepinephrine response nor with the increase in plasma immunoreactive glucagon levels. To further test whether these changes in plasma triglyceride levels were mediated via the sympathetic nervous system, hypoglycemia was evoked by insulin in subjects with traumatic spinal cord transactions. Two such subjects, who demonstrated sympathetic stimulation in response to hypoglycemia, had evidence of reduced VLDL secretion into plasma, while in two who had no evidence of an adrenergic response. VLDL secretion was not inhibited. Thus, acute lowering of plasma triglyceride concentrations by certain forms of stress appears to be mediated via the sympathetic nervous system."}
{"id": "PMID:221784", "title": "Metabolism of triglyceride in rabbit plasma low and high density lipoproteins: studies in vivo and in vitro.", "content": "The metabolism of triglyceride in the plasma low density lipoproteins (LDL) and high density lipoproteins (HDL) was studied in the normal-fed rabbit. Preparations of LDL and HDL la-eled with 3H in the triglyceride moiety were obtained from donor rabbits that had previously been injected with 3H-palmitic acid. These labeled lipoproteins were subsequently either reinjected into other rabbits or incubated in vitro with unlabeled lipoprotein fractions. In vivo, there were bidirectional transfers of 3H-triglyceride between the LDL and HDL, the rate of which considerably exceeded that of any irreversible removal from the plasma compartment. To a much lesser extent, there was also a transfer of 3H-triglyceride from both LDL and HDL to very low density lipoproteins (VLDL). In vitro, so long as the dialysed 1.21 g/ml infranate of serum was present there was a significant transfer of 3H-triglyceride from both LDL and HDL into each of the other lipoprotein fractions that in no case could be accounted for by a corresponding net transfer of triglyceride mass. It was concluded that the pools of triglyceride in LDL and HDL, and to a lesser extent in VLDL, comprise parts of a larger, progressively equilibrating pool.", "contents": "Metabolism of triglyceride in rabbit plasma low and high density lipoproteins: studies in vivo and in vitro. The metabolism of triglyceride in the plasma low density lipoproteins (LDL) and high density lipoproteins (HDL) was studied in the normal-fed rabbit. Preparations of LDL and HDL la-eled with 3H in the triglyceride moiety were obtained from donor rabbits that had previously been injected with 3H-palmitic acid. These labeled lipoproteins were subsequently either reinjected into other rabbits or incubated in vitro with unlabeled lipoprotein fractions. In vivo, there were bidirectional transfers of 3H-triglyceride between the LDL and HDL, the rate of which considerably exceeded that of any irreversible removal from the plasma compartment. To a much lesser extent, there was also a transfer of 3H-triglyceride from both LDL and HDL to very low density lipoproteins (VLDL). In vitro, so long as the dialysed 1.21 g/ml infranate of serum was present there was a significant transfer of 3H-triglyceride from both LDL and HDL into each of the other lipoprotein fractions that in no case could be accounted for by a corresponding net transfer of triglyceride mass. It was concluded that the pools of triglyceride in LDL and HDL, and to a lesser extent in VLDL, comprise parts of a larger, progressively equilibrating pool."}
{"id": "PMID:221785", "title": "Selective total removal of a growth-hormone-secreting adenoma: evidence that acromegaly is a primary pituitary disease.", "content": "Acromegaly is caused by hypersecretion of growth hormone by the pituitary. There is some debate as to whether the primary etiology of the disease is abnormal hypothalamic stimulation of the pituitary or a primary pituitary tumor. This paper presents a case of acromegaly in which growth hormone dynamics in response to stimulation and suppression tests were abnormal. After transsphenoidal adenomectomy of a small tumor, growth hormone levels returned to normal and suppression and stimulation test results reverted to normal within 1 wk postoperatively and remained normal for 2 yr. The findings suggest that the acromegaly in this case was due to a primary pituitary dysfunction. Microsurgical removal of growth-hormone-secreting tumors provides a unique opportunity to study the etiology of acromegaly.", "contents": "Selective total removal of a growth-hormone-secreting adenoma: evidence that acromegaly is a primary pituitary disease. Acromegaly is caused by hypersecretion of growth hormone by the pituitary. There is some debate as to whether the primary etiology of the disease is abnormal hypothalamic stimulation of the pituitary or a primary pituitary tumor. This paper presents a case of acromegaly in which growth hormone dynamics in response to stimulation and suppression tests were abnormal. After transsphenoidal adenomectomy of a small tumor, growth hormone levels returned to normal and suppression and stimulation test results reverted to normal within 1 wk postoperatively and remained normal for 2 yr. The findings suggest that the acromegaly in this case was due to a primary pituitary dysfunction. Microsurgical removal of growth-hormone-secreting tumors provides a unique opportunity to study the etiology of acromegaly."}
{"id": "PMID:221786", "title": "Na+ pump activity and nuclear T3 receptors in tissues of genetically obese (ob/ob) mice.", "content": "A dramatic reduction in ouabain-sensitive tissue respiration of obese mouse muscle and liver was observed, suggesting that Na+-transport-dependent calorigenesis is impaired in these animals. Additionally, a significantly depressed nuclear triiodothyronine binding capacity in liver and lung tissue was exhibited by obese mice. These data support the suggestion that the hypometabolism and hypothermia of the genetically obese mouse is a result of reduced Na+-pump-related thermogenesis; and further, provides evidence that this may be the consequence of reduced nuclear binding of triiodothyronine.", "contents": "Na+ pump activity and nuclear T3 receptors in tissues of genetically obese (ob/ob) mice. A dramatic reduction in ouabain-sensitive tissue respiration of obese mouse muscle and liver was observed, suggesting that Na+-transport-dependent calorigenesis is impaired in these animals. Additionally, a significantly depressed nuclear triiodothyronine binding capacity in liver and lung tissue was exhibited by obese mice. These data support the suggestion that the hypometabolism and hypothermia of the genetically obese mouse is a result of reduced Na+-pump-related thermogenesis; and further, provides evidence that this may be the consequence of reduced nuclear binding of triiodothyronine."}
{"id": "PMID:221787", "title": "Changes in lipoprotein composition during the menstrual cycle.", "content": "Composition of major plasma lipoproteins was studied in 14 normal women during different phases of the menstrual cycle for three consecutive months. The results were compared to measurements in ten normal age-matched men for a comparable period, to delineate possible sex differences in lipoprotein metabolism in young adults. Blood samples were obtained every 3--5 days after a 14-hr overnight fast and processed for determinations of total plasma cholesterol, LDL- and HDL-cholesterol, and apoproteins B and A-1. In premenopausal women, a significant, 10%--25% cyclical suppression of total plasma cholesterol, LDL-Chol, and LDL-apoB occurred during the luteal phase, which was significantly lower than unchanging concentrations found in men at any time interval. HDL-Chol remained in a significantly higher fixed concentration range in the female subjects as compared to the men. These sex differences in lipoprotein metabolism may have relevance to the reduced susceptibility of premenopausal women to atherosclerosis.", "contents": "Changes in lipoprotein composition during the menstrual cycle. Composition of major plasma lipoproteins was studied in 14 normal women during different phases of the menstrual cycle for three consecutive months. The results were compared to measurements in ten normal age-matched men for a comparable period, to delineate possible sex differences in lipoprotein metabolism in young adults. Blood samples were obtained every 3--5 days after a 14-hr overnight fast and processed for determinations of total plasma cholesterol, LDL- and HDL-cholesterol, and apoproteins B and A-1. In premenopausal women, a significant, 10%--25% cyclical suppression of total plasma cholesterol, LDL-Chol, and LDL-apoB occurred during the luteal phase, which was significantly lower than unchanging concentrations found in men at any time interval. HDL-Chol remained in a significantly higher fixed concentration range in the female subjects as compared to the men. These sex differences in lipoprotein metabolism may have relevance to the reduced susceptibility of premenopausal women to atherosclerosis."}
{"id": "PMID:221788", "title": "High density lipoprotein cholesterol and coronary artery occlusion.", "content": "The relationship between the levels of high density lipoprotein cholesterol (HDLC) and the extent of coronary artery occlusion (ascertained by arteriography) was studied in four hundred male patients. The group with HDLC levels over 50 mg/dl showed a significantly lower coronary artery occlusion score and lower plasma triglyceride levels than the patients with HDLC levels less than 35 mg/dl. The former group also imbibed more alcohol and had less smoking experience.", "contents": "High density lipoprotein cholesterol and coronary artery occlusion. The relationship between the levels of high density lipoprotein cholesterol (HDLC) and the extent of coronary artery occlusion (ascertained by arteriography) was studied in four hundred male patients. The group with HDLC levels over 50 mg/dl showed a significantly lower coronary artery occlusion score and lower plasma triglyceride levels than the patients with HDLC levels less than 35 mg/dl. The former group also imbibed more alcohol and had less smoking experience."}
{"id": "PMID:221789", "title": "Apolipoprotein A-I synthesis and secretion by cultured human intestinal mucosa.", "content": "Cultured human duodenojejunal mucosa was used to study the synthesis and secretion of apoprotein A-I (apoA-I), the major protein constituent of plasma high density lipoproteins. ApoA-I, measured by radioimmunoassay, was secreted continuously into the culture medium over a period of 24 hr. The highest rate was found in the first two hours (34.6 +/- 3.0 ng/mg tissue X hr, mean +/- SE, n = 24). Secretion rate decreased with incubation time, while changes of culture medium increased the rate. ApoA-I secretion was enhanced three- to fourfold by micellar lipid solution and was inhibited by puromycin, ApoA-I synthesis was confirmed by incorporation of 14C-leucine into this apoprotein. The specific activity of apoA-I in medium ultracentrifugal fractions (d less than 1.019 and d = 1.063--1.21 g/ml) was calculated from quantitative data obtained by radioimmunoassay and radioassay of apoA-I separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and found to be about 12 mCi/mmol. These observations indicate that cultured human intestinal mucosa is capable of secreting newly synthesized apoA-I. Organ culture may thus serve as a tool for studying the regulating mechanisms for the synthesis and secretion of this important apoprotein.", "contents": "Apolipoprotein A-I synthesis and secretion by cultured human intestinal mucosa. Cultured human duodenojejunal mucosa was used to study the synthesis and secretion of apoprotein A-I (apoA-I), the major protein constituent of plasma high density lipoproteins. ApoA-I, measured by radioimmunoassay, was secreted continuously into the culture medium over a period of 24 hr. The highest rate was found in the first two hours (34.6 +/- 3.0 ng/mg tissue X hr, mean +/- SE, n = 24). Secretion rate decreased with incubation time, while changes of culture medium increased the rate. ApoA-I secretion was enhanced three- to fourfold by micellar lipid solution and was inhibited by puromycin, ApoA-I synthesis was confirmed by incorporation of 14C-leucine into this apoprotein. The specific activity of apoA-I in medium ultracentrifugal fractions (d less than 1.019 and d = 1.063--1.21 g/ml) was calculated from quantitative data obtained by radioimmunoassay and radioassay of apoA-I separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and found to be about 12 mCi/mmol. These observations indicate that cultured human intestinal mucosa is capable of secreting newly synthesized apoA-I. Organ culture may thus serve as a tool for studying the regulating mechanisms for the synthesis and secretion of this important apoprotein."}
{"id": "PMID:221790", "title": "Relationships among cardiorespiratory fitness, regular physical activity, and plasma lipids in young adults.", "content": "Relationships between physical activity and plasma lipids and between cardiorespiratory (CR) fitness and plasma lipids were investigated in 152 young adults. There were no significant correlations in either females or males between the physical activity indicators and any of the plasma lipids investigated. CR fitness, as indicated by treadmill test duration, showed a small but statistically significant sexes, an association that may well underestimate the true relationship because of the limitations of the study. Plasma triglycerides were negatively correlated with CR fitness in the males. It was suggested that the two fitness components, aerobic capacity and percent fat, may be related to certain plasma lipids differently in males than in females.", "contents": "Relationships among cardiorespiratory fitness, regular physical activity, and plasma lipids in young adults. Relationships between physical activity and plasma lipids and between cardiorespiratory (CR) fitness and plasma lipids were investigated in 152 young adults. There were no significant correlations in either females or males between the physical activity indicators and any of the plasma lipids investigated. CR fitness, as indicated by treadmill test duration, showed a small but statistically significant sexes, an association that may well underestimate the true relationship because of the limitations of the study. Plasma triglycerides were negatively correlated with CR fitness in the males. It was suggested that the two fitness components, aerobic capacity and percent fat, may be related to certain plasma lipids differently in males than in females."}
{"id": "PMID:221791", "title": "Cell composition and drug resistance in Escherichia coli.", "content": "Resistance of micro-organisms to antibacterial drugs which cannot be attributed to a genetic change may often be traced to phenotypic changes in cell composition caused by differing growth conditions. To investigate an aspect of this attribute E. coli NCTC 86 was grown on a simple synthetic media containing alanine or cystine and, as a control, in nutrient broth. Cells grown on the media containing alanine and cystine showed a depleted total extractable lipid and phospholipid content. Phosphatidylethanolamine was notably reduced in both cases. Electrophoretic studies revealed a reduction in the surface lipid of cells grown on the simple synthetic media, while electron microscopy revealed defects in the cell wall of the cells grown on alanine. The total protein content of cells grown on alanine was reduced, whereas cells grown on the cystine showed an enhanced total carbohydrate content. Lipopolysaccharide synthesis was possibly also affected as judged by 2-keto-3-desoxy-D-manno-octonic aid content. The action of p-tertiary amylphenol, cetrimide and polymyxin B sulphate, showed that cells grown on the media containing alanine were most susceptible to the action of the phenol and cetrimide, whilst cells grown on the media containing cystine were most resistant to the action of polymyxin.", "contents": "Cell composition and drug resistance in Escherichia coli. Resistance of micro-organisms to antibacterial drugs which cannot be attributed to a genetic change may often be traced to phenotypic changes in cell composition caused by differing growth conditions. To investigate an aspect of this attribute E. coli NCTC 86 was grown on a simple synthetic media containing alanine or cystine and, as a control, in nutrient broth. Cells grown on the media containing alanine and cystine showed a depleted total extractable lipid and phospholipid content. Phosphatidylethanolamine was notably reduced in both cases. Electrophoretic studies revealed a reduction in the surface lipid of cells grown on the simple synthetic media, while electron microscopy revealed defects in the cell wall of the cells grown on alanine. The total protein content of cells grown on alanine was reduced, whereas cells grown on the cystine showed an enhanced total carbohydrate content. Lipopolysaccharide synthesis was possibly also affected as judged by 2-keto-3-desoxy-D-manno-octonic aid content. The action of p-tertiary amylphenol, cetrimide and polymyxin B sulphate, showed that cells grown on the media containing alanine were most susceptible to the action of the phenol and cetrimide, whilst cells grown on the media containing cystine were most resistant to the action of polymyxin."}
{"id": "PMID:221795", "title": "Primary hepatocellular carcinoma in Australia: Aetiological considerations.", "content": "This is a study of aetiological associations in patients with primary hepatocellular carcinoma (PHC). Thirty new patients with PHC were seen in a five-year period. The most common aetiological association was alcoholic cirrhosis. This was implicated in the development of PHC in 13 patients. However, since the introduction of radioimmunoassay for hepatitis B surface antigen (HBsAg) there have been six patients with HBsAg-associated PHC. Thus, for the first time, an association of hepatitis B virus with PHC is described in this country.", "contents": "Primary hepatocellular carcinoma in Australia: Aetiological considerations. This is a study of aetiological associations in patients with primary hepatocellular carcinoma (PHC). Thirty new patients with PHC were seen in a five-year period. The most common aetiological association was alcoholic cirrhosis. This was implicated in the development of PHC in 13 patients. However, since the introduction of radioimmunoassay for hepatitis B surface antigen (HBsAg) there have been six patients with HBsAg-associated PHC. Thus, for the first time, an association of hepatitis B virus with PHC is described in this country."}
{"id": "PMID:221804", "title": "[Influence of dental caries prophylaxis using fluor-vigantoletten 1000 on plasma fluoride levels in infants (author's transl)].", "content": "A group of 57 newborns was divided into two: group I (27 subjects) received solely 1,000 I.U. vitamin D3 per day for 6 months, whereas group II (30 subjects) were given a combination of 1,000 I.U. vitamin D3 and 0.25 mg fluoride. At the end of the time of observation there was a significant difference between the plasma concentrations in the two groups. The median value was 13.06 microgram/l (range: 8:18-39.4 microgram/l) in group I and 16.54 microgram/l (range: 9.9--41.2 microgram/l) in group II. Fluoride is obviously available to infants when administered in combination with Vitamin D3. In addition, it could be proven, that after 6 month administration of fluoride there are no signs of cumulation, overdosage or even intoxication.", "contents": "[Influence of dental caries prophylaxis using fluor-vigantoletten 1000 on plasma fluoride levels in infants (author's transl)]. A group of 57 newborns was divided into two: group I (27 subjects) received solely 1,000 I.U. vitamin D3 per day for 6 months, whereas group II (30 subjects) were given a combination of 1,000 I.U. vitamin D3 and 0.25 mg fluoride. At the end of the time of observation there was a significant difference between the plasma concentrations in the two groups. The median value was 13.06 microgram/l (range: 8:18-39.4 microgram/l) in group I and 16.54 microgram/l (range: 9.9--41.2 microgram/l) in group II. Fluoride is obviously available to infants when administered in combination with Vitamin D3. In addition, it could be proven, that after 6 month administration of fluoride there are no signs of cumulation, overdosage or even intoxication."}
{"id": "PMID:221800", "title": "[Rotatory mobility and intermolecular reactions of serum albumin studied using the spin-probe method].", "content": "Dependence of the rotational mobility of bovine serum albumin on the protein concentration in solution has been studied by means of nitroxyl radical tightly bound to the protein. The rotational correlation time of radical, bound with protein for weak solution has been compared with the theoretical values of correlation times for protein monomer, calculated in terms of its hydration and deviation from the spherical shape. A conclusion about radical orientation relatively to the protein molecule has been drawn from this comparison. The concentration dependence of ratational correlation time for radical, bound with protein, was explained by the protein dimerization in solution. A conclusion has been drawn about the stability of intramolecular structure of serum albumin during its dimerization on the basis of the stability of anisotropic hyperfine constants of adsorbed radical.", "contents": "[Rotatory mobility and intermolecular reactions of serum albumin studied using the spin-probe method]. Dependence of the rotational mobility of bovine serum albumin on the protein concentration in solution has been studied by means of nitroxyl radical tightly bound to the protein. The rotational correlation time of radical, bound with protein for weak solution has been compared with the theoretical values of correlation times for protein monomer, calculated in terms of its hydration and deviation from the spherical shape. A conclusion about radical orientation relatively to the protein molecule has been drawn from this comparison. The concentration dependence of ratational correlation time for radical, bound with protein, was explained by the protein dimerization in solution. A conclusion has been drawn about the stability of intramolecular structure of serum albumin during its dimerization on the basis of the stability of anisotropic hyperfine constants of adsorbed radical."}
{"id": "PMID:221801", "title": "[Possible nature of negative cooperation in D-glyceraldehyde-3-phosphate dehydrogenase].", "content": "Some considerations concerning the detailed mechanism of negative cooperativity in GPD are proposed. The hypothesis represents a modification of the sequential model (Koshland et al.) taking into account last experimental data about the binding of NAD analogs and fragments. Two main facts have been used as a basis for the model: 1. Neither ADP-ribose nor nicotinamide mononucleotide (NMN) fragments of NAD show negative cooperative binding to GPD. 2. Neither modifications of adenine and nicotinamide part of NAD (epsilon-NAD, hypoxantine-NAD, oxidized and reduced-NAD) nor enzyme modifications by various reagents acting in the catalytic site affect considerably the cooperativity of coenzyme binding although the affinity between enzyme and coenzyme (analogs) substantially changes depending on the nature of modification. Probably the structural integrity of a coenzyme molecule is necessary for the cooperative binding to GPD. On the other hand, numerous modification studies can be interpreted as proving the absence of direct participation of adenine and nicotinamide rings in the mechanism of negative interactions between NAD-binding sites. It appears reasonable to assume that direct or indirect interactions of riboseAD and pyrophosphate groups of NAD with the \"loop\" of adjacent subunit might be necessary for the tight coenzyme binding to the first active site of the r-dimer(s) symmetric across the R-axis. After the tight binding of the first NAD molecule on r-dimer with the \"loop\" participation, the symmetrical movement of second \"loop\" might be highly restricted. It was postulated that only asymmetric conformational transition is possible in contact areas between subunits across the R-axis. Such asymmetric rearrangement can explain the nonequivalent binding of NAD to a prior symmetric dimmer(s).", "contents": "[Possible nature of negative cooperation in D-glyceraldehyde-3-phosphate dehydrogenase]. Some considerations concerning the detailed mechanism of negative cooperativity in GPD are proposed. The hypothesis represents a modification of the sequential model (Koshland et al.) taking into account last experimental data about the binding of NAD analogs and fragments. Two main facts have been used as a basis for the model: 1. Neither ADP-ribose nor nicotinamide mononucleotide (NMN) fragments of NAD show negative cooperative binding to GPD. 2. Neither modifications of adenine and nicotinamide part of NAD (epsilon-NAD, hypoxantine-NAD, oxidized and reduced-NAD) nor enzyme modifications by various reagents acting in the catalytic site affect considerably the cooperativity of coenzyme binding although the affinity between enzyme and coenzyme (analogs) substantially changes depending on the nature of modification. Probably the structural integrity of a coenzyme molecule is necessary for the cooperative binding to GPD. On the other hand, numerous modification studies can be interpreted as proving the absence of direct participation of adenine and nicotinamide rings in the mechanism of negative interactions between NAD-binding sites. It appears reasonable to assume that direct or indirect interactions of riboseAD and pyrophosphate groups of NAD with the \"loop\" of adjacent subunit might be necessary for the tight coenzyme binding to the first active site of the r-dimer(s) symmetric across the R-axis. After the tight binding of the first NAD molecule on r-dimer with the \"loop\" participation, the symmetrical movement of second \"loop\" might be highly restricted. It was postulated that only asymmetric conformational transition is possible in contact areas between subunits across the R-axis. Such asymmetric rearrangement can explain the nonequivalent binding of NAD to a prior symmetric dimmer(s)."}
{"id": "PMID:221802", "title": "[Kinetics of reactions in polyenzyme systems. III. Electron transport processes].", "content": "Kinetic relationships of electron transport processes in biological systems have been analysed. Formal-kinetic description and discrimination of the two main models of electron transport processes in systems of homogeneously distributed carriers and in systems of structurally bound carriers is presented including steady-state and non-steady-state reaction kinetics. Methods of determination of limit-stage rate constant and rate constants for all elementary steps of the reaction are given. Dependencies of the degree of electron carriers reduction on donor and acceptor concentrations and the influence of reduction or oxidation of carriers on the kinetic properties of electron transport chain (electron influence factor) in the system of structurally-bound carriers have been analyzed. On the basis of kinetic models a molecular-kinetic interpretation of activation effect of mitochondrial respiratory chain during the process of electron transport is offered.", "contents": "[Kinetics of reactions in polyenzyme systems. III. Electron transport processes]. Kinetic relationships of electron transport processes in biological systems have been analysed. Formal-kinetic description and discrimination of the two main models of electron transport processes in systems of homogeneously distributed carriers and in systems of structurally bound carriers is presented including steady-state and non-steady-state reaction kinetics. Methods of determination of limit-stage rate constant and rate constants for all elementary steps of the reaction are given. Dependencies of the degree of electron carriers reduction on donor and acceptor concentrations and the influence of reduction or oxidation of carriers on the kinetic properties of electron transport chain (electron influence factor) in the system of structurally-bound carriers have been analyzed. On the basis of kinetic models a molecular-kinetic interpretation of activation effect of mitochondrial respiratory chain during the process of electron transport is offered."}
{"id": "PMID:221805", "title": "The terminal innervation pattern in polymyositis: a histochemical and SFEMG study.", "content": "Changes of the terminal innervation pattern in polymyositis were studied in nine patients using single fiber electromyography (SFEMG) and histochemical investigations of muscle biopsies. In all patients, and in 16 out of 18 muscles studied, reinnervation was found. The preceding denervation could be caused either by segmental necrosis of the muscle fiber that disconnects one part of the fiber from the end-plate region or by direct intramuscular nerve involvement.", "contents": "The terminal innervation pattern in polymyositis: a histochemical and SFEMG study. Changes of the terminal innervation pattern in polymyositis were studied in nine patients using single fiber electromyography (SFEMG) and histochemical investigations of muscle biopsies. In all patients, and in 16 out of 18 muscles studied, reinnervation was found. The preceding denervation could be caused either by segmental necrosis of the muscle fiber that disconnects one part of the fiber from the end-plate region or by direct intramuscular nerve involvement."}
{"id": "PMID:221809", "title": "Increased glomerular filtration rate after converting-enzyme inhibition in essential hypertension.", "content": "To test the influence of an inhibitor of angiotensin-converting enzyme, teprotide (SQ 20881), we administered it to seven patients with essential hypertension and normal renal function and nine with an unequivocal reduction in creatinine clearance, caused by bilateral renal-artery stenosis in two and by essential hypertension in seven. Despite the fall in blood pressure (112.7 +/- 4.5 to 100.3 +/- 3.9 mm Hg, mean +/- S.E.M., P less than 0.01), there were prompt increases in both creatinine clearance (95.9 +/- 10.5 to 109.9 +/- 9.5 ml per minute per 1.73 m2 of body-surface area, P less than 0.01) and sodium excretion (17.0 +/- 5.9 to 31.7 +/- 7.2 mumol per minute, P less than 0.01) in patients with essential hypertension. The increase in glomerular filtration rate was most striking, averaging 33 per cent (66.0 +/- 10.3 to 88.0 +/- 9.2 ml per minute per 1.73 m2, P less than 0.001) in patients in whom an initial reduction was evident and hypertension was more severe. These observations suggest that a functional element, perhaps involving angiotensin-mediated renal vasoconstriction, frequently has a role in the reduction in glomerular filtration rate that occurs in essential hypertension. This class of agent may improve renal excretory function as it controls hypertension.", "contents": "Increased glomerular filtration rate after converting-enzyme inhibition in essential hypertension. To test the influence of an inhibitor of angiotensin-converting enzyme, teprotide (SQ 20881), we administered it to seven patients with essential hypertension and normal renal function and nine with an unequivocal reduction in creatinine clearance, caused by bilateral renal-artery stenosis in two and by essential hypertension in seven. Despite the fall in blood pressure (112.7 +/- 4.5 to 100.3 +/- 3.9 mm Hg, mean +/- S.E.M., P less than 0.01), there were prompt increases in both creatinine clearance (95.9 +/- 10.5 to 109.9 +/- 9.5 ml per minute per 1.73 m2 of body-surface area, P less than 0.01) and sodium excretion (17.0 +/- 5.9 to 31.7 +/- 7.2 mumol per minute, P less than 0.01) in patients with essential hypertension. The increase in glomerular filtration rate was most striking, averaging 33 per cent (66.0 +/- 10.3 to 88.0 +/- 9.2 ml per minute per 1.73 m2, P less than 0.001) in patients in whom an initial reduction was evident and hypertension was more severe. These observations suggest that a functional element, perhaps involving angiotensin-mediated renal vasoconstriction, frequently has a role in the reduction in glomerular filtration rate that occurs in essential hypertension. This class of agent may improve renal excretory function as it controls hypertension."}
{"id": "PMID:221810", "title": "Treatment of chronic congestive heart failure with captopril, an oral inhibitor of angiotensin-converting enzyme.", "content": "The renin-angiotensin system is thought to maintain elevated systemic vascular resistance in heart failure. The hemodynamic effects of captopril (SQ 14225), an oral inhibitor of angiotensin-converting enzyme, were measured in 10 patients with stable congestive heart failure poorly controlled by digitalis and diuretics. At single daily doses of 25 to 150 mg, the cardiac index rose from 1.75 +/- 0.18 to 2.27 +/- 0.39 (mean +/- S.D.) liters per minute per square meter (P less than 0.001), and pulmonary-wedge pressure fell from 26.5 +/- 7.5 to 17.3 +/- 6.1 mm Hg (P less than 0.01). Systemic vascular resistance decreased from 2006 +/- 300 to 1393 +/- 238 dyne seconds per centimeter (P less than 0.001), and mean arterial pressure fell from 83.7 +/- 7.0 to 70.3 +/- 9.9 mm Hg (P less than 0.001) (mean +/- S.D.). Heart rate did not change appreciably. Hemodynamic alterations peaked at 90 minutes and persisted for three to four hours. Control plasma renin activity ranged from 1.1 to 7.3 ng per milliliter per hour and did not correlate with changes in hemodynamic values. Three patients on long-term treatment maintained clinical improvement. Although its mechanism of action has not been completely elucidated, captopril may prove useful in the treatment of chronic congestive heart failure.", "contents": "Treatment of chronic congestive heart failure with captopril, an oral inhibitor of angiotensin-converting enzyme. The renin-angiotensin system is thought to maintain elevated systemic vascular resistance in heart failure. The hemodynamic effects of captopril (SQ 14225), an oral inhibitor of angiotensin-converting enzyme, were measured in 10 patients with stable congestive heart failure poorly controlled by digitalis and diuretics. At single daily doses of 25 to 150 mg, the cardiac index rose from 1.75 +/- 0.18 to 2.27 +/- 0.39 (mean +/- S.D.) liters per minute per square meter (P less than 0.001), and pulmonary-wedge pressure fell from 26.5 +/- 7.5 to 17.3 +/- 6.1 mm Hg (P less than 0.01). Systemic vascular resistance decreased from 2006 +/- 300 to 1393 +/- 238 dyne seconds per centimeter (P less than 0.001), and mean arterial pressure fell from 83.7 +/- 7.0 to 70.3 +/- 9.9 mm Hg (P less than 0.001) (mean +/- S.D.). Heart rate did not change appreciably. Hemodynamic alterations peaked at 90 minutes and persisted for three to four hours. Control plasma renin activity ranged from 1.1 to 7.3 ng per milliliter per hour and did not correlate with changes in hemodynamic values. Three patients on long-term treatment maintained clinical improvement. Although its mechanism of action has not been completely elucidated, captopril may prove useful in the treatment of chronic congestive heart failure."}
{"id": "PMID:221812", "title": "Prevention of reactivated herpes simplex infection by human leukocyte interferon after operation on the trigeminal root.", "content": "Microneurosurgical procedures on the trigeminal-nerve root are often followed by reactivation of herpes simplex virus infection, manifested by herpes labialis or oropharyngeal herpesvirus shedding or both. In a double-blind study of the ability of human leukocyte interferon to prevent this reactivation, patients with a history of herpes labialis were given 7 x 10(4) U of interferon per kilogram of body weight per day or placebo for five days beginning on the day before operation. In 18 patients treated with placebo, herpes labialis developed in 10, and virus shedding in the oropharynx in 15. In 19 patients treated with interferon, lesions developed in five, and shedding in eight. The frequency of reactivation as measured by lesions or positive throat cultures or both was significantly reduced by interferon (P less than 0.05). Of 127 daily throat-wash cultures in the placebo group, 42 per cent were positive for herpesvirus, but of 134 in the interferon group, only 9 per cent were positive (P less than 0.001). We conclude that interferon at a well-tolerated dosage reduces reactivation of latent herpes simplex virus infection after a potent operative stimulus.", "contents": "Prevention of reactivated herpes simplex infection by human leukocyte interferon after operation on the trigeminal root. Microneurosurgical procedures on the trigeminal-nerve root are often followed by reactivation of herpes simplex virus infection, manifested by herpes labialis or oropharyngeal herpesvirus shedding or both. In a double-blind study of the ability of human leukocyte interferon to prevent this reactivation, patients with a history of herpes labialis were given 7 x 10(4) U of interferon per kilogram of body weight per day or placebo for five days beginning on the day before operation. In 18 patients treated with placebo, herpes labialis developed in 10, and virus shedding in the oropharynx in 15. In 19 patients treated with interferon, lesions developed in five, and shedding in eight. The frequency of reactivation as measured by lesions or positive throat cultures or both was significantly reduced by interferon (P less than 0.05). Of 127 daily throat-wash cultures in the placebo group, 42 per cent were positive for herpesvirus, but of 134 in the interferon group, only 9 per cent were positive (P less than 0.001). We conclude that interferon at a well-tolerated dosage reduces reactivation of latent herpes simplex virus infection after a potent operative stimulus."}
{"id": "PMID:221816", "title": "Rotavirus infection in adults. Results of a prospective family study.", "content": "To study the epidemiologic and clinical features of rotavirus infections, we enrolled 98 families in a prospective study of diarrhea in households with newborn children. Families were seen at three-month intervals and whenever ill. The mean follow-up period was 16.4 months. Rotavirus infections were documented by electron microscopy of feces, indirect fluorescent-antibody assays in serum or both. The 43 infections identified in adults represented an attack rate of 0.17 per adult per year. Ninety-three per cent of these infections occurred from November through May. Seventeen adults had gastrointestinal symptoms, most often diarrhea (in 14) or abdominal cramps (in 11). Rotavirus infections occurred in 36 of 102 adults whose children had rotavirus infection, as compared with four of 86 without infected children (P less than 0.001). Serum rotavirus antibody did not correlate with a reduced risk of infection or symptomatic disease. Rotavirus is a mild but common infection in parents of young children.", "contents": "Rotavirus infection in adults. Results of a prospective family study. To study the epidemiologic and clinical features of rotavirus infections, we enrolled 98 families in a prospective study of diarrhea in households with newborn children. Families were seen at three-month intervals and whenever ill. The mean follow-up period was 16.4 months. Rotavirus infections were documented by electron microscopy of feces, indirect fluorescent-antibody assays in serum or both. The 43 infections identified in adults represented an attack rate of 0.17 per adult per year. Ninety-three per cent of these infections occurred from November through May. Seventeen adults had gastrointestinal symptoms, most often diarrhea (in 14) or abdominal cramps (in 11). Rotavirus infections occurred in 36 of 102 adults whose children had rotavirus infection, as compared with four of 86 without infected children (P less than 0.001). Serum rotavirus antibody did not correlate with a reduced risk of infection or symptomatic disease. Rotavirus is a mild but common infection in parents of young children."}
{"id": "PMID:221817", "title": "Endogenous mammary tumour virus DNA varies among wild mice and segregates during inbreeding.", "content": "Proviruses of the mouse mammary tumour virus (MMTV) endogenous to normal mice can be identified by molecular hybridisation and distinguished using restriction endonucleases. Feral mice display marked heterogeneity with respect to the number of copies and the sites of insertion of endogenous MMTV-specific DNA, with occasional mice apparently free of MMTV DNA. Several different MMTV proviruses present in laboratory mice have segregated like stable, independent genetic elements during the inbreeding which followed a cross between Bagg albino and DBA mice 60 years ago. The results favour the hypothesis that endogenous proviruses have been established by multiple, independent infections of germ cells rather than by somatic mutation of ancestral proviruses or of cellular genes.", "contents": "Endogenous mammary tumour virus DNA varies among wild mice and segregates during inbreeding. Proviruses of the mouse mammary tumour virus (MMTV) endogenous to normal mice can be identified by molecular hybridisation and distinguished using restriction endonucleases. Feral mice display marked heterogeneity with respect to the number of copies and the sites of insertion of endogenous MMTV-specific DNA, with occasional mice apparently free of MMTV DNA. Several different MMTV proviruses present in laboratory mice have segregated like stable, independent genetic elements during the inbreeding which followed a cross between Bagg albino and DBA mice 60 years ago. The results favour the hypothesis that endogenous proviruses have been established by multiple, independent infections of germ cells rather than by somatic mutation of ancestral proviruses or of cellular genes."}
{"id": "PMID:221818", "title": "Nucleotide sequence of cloned cDNA for bovine corticotropin-beta-lipotropin precursor.", "content": "The nucleotide sequence of a 1,091-base pair cloned cDNA insert encoding bovine corticotropin-beta-lipotropin precursor mRNA is reported. The corresponding amino acid sequence indicates that the precursor protein consists of repetitive units and includes a third melanotropin sequence in its cryptic portion. Pairs of lysine and arginine residues separate the component peptides of the precursor.", "contents": "Nucleotide sequence of cloned cDNA for bovine corticotropin-beta-lipotropin precursor. The nucleotide sequence of a 1,091-base pair cloned cDNA insert encoding bovine corticotropin-beta-lipotropin precursor mRNA is reported. The corresponding amino acid sequence indicates that the precursor protein consists of repetitive units and includes a third melanotropin sequence in its cryptic portion. Pairs of lysine and arginine residues separate the component peptides of the precursor."}
{"id": "PMID:221830", "title": "Modulation of the two promoters of the galactose operon of Escherichia coli.", "content": "The gal operon of Escherichia coli is controlled by two independent promotors--one is activated and the other inhibited by cyclic AMP and cyclic AMP receptor protein. The two promotors are modulated, however, by the same operator locus and receptor protein.", "contents": "Modulation of the two promoters of the galactose operon of Escherichia coli. The gal operon of Escherichia coli is controlled by two independent promotors--one is activated and the other inhibited by cyclic AMP and cyclic AMP receptor protein. The two promotors are modulated, however, by the same operator locus and receptor protein."}
{"id": "PMID:221831", "title": "Unusual location and function of the operator in the Escherichia coli galactose operon.", "content": "The operator of the gal operon is located about 60 base pairs preceding the startpoints of the transcription of the two gal promoters. This location contrasts with the location of the operator in other phage or bacterial operons where the repressor binds more closely to the respective transcription initiation sites. Models explaining how the repressor-operator interactions may control the two gal promoters are presented.", "contents": "Unusual location and function of the operator in the Escherichia coli galactose operon. The operator of the gal operon is located about 60 base pairs preceding the startpoints of the transcription of the two gal promoters. This location contrasts with the location of the operator in other phage or bacterial operons where the repressor binds more closely to the respective transcription initiation sites. Models explaining how the repressor-operator interactions may control the two gal promoters are presented."}
{"id": "PMID:221835", "title": "Coated pits, coated vesicles, and receptor-mediated endocytosis.", "content": "Proteins and peptides can enter cells by receptor-mediated endocytosis, a coupled process by which selected extracellular proteins or peptides are first bound to specific cell surface receptors and then rapidly internalised by the cell. Internalisation follows clustering of the receptors in specialised regions of the cell surface called coated pits that invaginate to form intracellular coated vesicles. It is now recognised that receptor-mediated endocytosis has a fundamental role in the growth, nutrition and differentiation of animal cells.", "contents": "Coated pits, coated vesicles, and receptor-mediated endocytosis. Proteins and peptides can enter cells by receptor-mediated endocytosis, a coupled process by which selected extracellular proteins or peptides are first bound to specific cell surface receptors and then rapidly internalised by the cell. Internalisation follows clustering of the receptors in specialised regions of the cell surface called coated pits that invaginate to form intracellular coated vesicles. It is now recognised that receptor-mediated endocytosis has a fundamental role in the growth, nutrition and differentiation of animal cells."}
{"id": "PMID:221844", "title": "The effect of naloxone on cerebellar cGMP content. A possible GABA-antagonistic action?", "content": "Naloxone in high doses (60--240 mg/kg i.p.) produced a dose-dependent increase in cerebellar cGMP content of mice. The rise in cGMP content reached its maximum within 5 min and was of short duration. Short-lasting episodes of clonic seizures were noted after 240 mg/kg naloxone. Low doses of naloxone (5--10 mg/kg) had no effect on cerebellar cGMP content, but markedly potentiated the increase in cGMP induced by isoniazid. On the other hand, naloxone (5 mg/kg) partially antagonized the fall in cGMP elicited by diazepam, but had only a slight effect on the action of pentobarbital (30 mg/kg i.p.). These results support the assumption proposed by other authors that naloxone exerts GABA antagonistic effects aside from the potent opiate receptor antagonistic activity.", "contents": "The effect of naloxone on cerebellar cGMP content. A possible GABA-antagonistic action? Naloxone in high doses (60--240 mg/kg i.p.) produced a dose-dependent increase in cerebellar cGMP content of mice. The rise in cGMP content reached its maximum within 5 min and was of short duration. Short-lasting episodes of clonic seizures were noted after 240 mg/kg naloxone. Low doses of naloxone (5--10 mg/kg) had no effect on cerebellar cGMP content, but markedly potentiated the increase in cGMP induced by isoniazid. On the other hand, naloxone (5 mg/kg) partially antagonized the fall in cGMP elicited by diazepam, but had only a slight effect on the action of pentobarbital (30 mg/kg i.p.). These results support the assumption proposed by other authors that naloxone exerts GABA antagonistic effects aside from the potent opiate receptor antagonistic activity."}
{"id": "PMID:221846", "title": "Inhibition and promotion of growth of B77-virus-induced rat tumor with KCl-solubilized tumor cell components.", "content": "Rats were immunized with a single and repeated doses (1.0 mg of protein per dose per animal) of KCl-solubilized thymus and avian sarcoma virus B77-induced rat tumor cells LWF B77 prior to challenge with the same tumor cells. Results obtained showed that single administration of KCl-solubilized tumor cell material resulted in inhibition of growth of syngeneic tumor cells. Repeated inoculations of the same material, however, promoted tumor growth. Possible explanation of this dual effect is discussed.", "contents": "Inhibition and promotion of growth of B77-virus-induced rat tumor with KCl-solubilized tumor cell components. Rats were immunized with a single and repeated doses (1.0 mg of protein per dose per animal) of KCl-solubilized thymus and avian sarcoma virus B77-induced rat tumor cells LWF B77 prior to challenge with the same tumor cells. Results obtained showed that single administration of KCl-solubilized tumor cell material resulted in inhibition of growth of syngeneic tumor cells. Repeated inoculations of the same material, however, promoted tumor growth. Possible explanation of this dual effect is discussed."}
{"id": "PMID:221847", "title": "Increased pathogenicity of avian sarcoma virus B77 in cyclophosphamide treated chickens.", "content": "The course of sarcoma development was studied in cyclophosphamide treated and control chickens injected with avian sarcoma virus B77 (B77V). It was found that the incidence of sarcomas was the same for both groups of birds. Progressive growth of sarcomas as well as high tumor mortality was observed in drug treated birds, whereas frequent regressions occurred in controls. The drug treatment after B77V infection did not change the response patterns and no cytostatic effect of the drug was observed. Cyclophosphamide treatment improved the rescuability of B77V genome from the transformed virogenic mouse and rat cells in vivo.", "contents": "Increased pathogenicity of avian sarcoma virus B77 in cyclophosphamide treated chickens. The course of sarcoma development was studied in cyclophosphamide treated and control chickens injected with avian sarcoma virus B77 (B77V). It was found that the incidence of sarcomas was the same for both groups of birds. Progressive growth of sarcomas as well as high tumor mortality was observed in drug treated birds, whereas frequent regressions occurred in controls. The drug treatment after B77V infection did not change the response patterns and no cytostatic effect of the drug was observed. Cyclophosphamide treatment improved the rescuability of B77V genome from the transformed virogenic mouse and rat cells in vivo."}
{"id": "PMID:221848", "title": "Protein synthesis in tumor host. II. Increased activity of peptide elongation factor 1 in experimental rat tumors and in host liver.", "content": "Both peptide elongation factors were purified from Zajdela and Walker tumors and from the host and normal liver. The activity of peptide elongation factor 1 from tumor tissues in promoting the binding of phenylalanyl-tRNA to ribosomes was significantly higher than that of normal liver. Also preparations from the host liver were markedly more active when compared with the corresponding factor from normal liver. Poly(U)-dependent phenylalanine polymerization was enhanced in subcellular systems containing elongation factor 1 from tumors or host liver. No differences were found between preparations of elongation factor 2 isolated from various sources. Tumor ribosomes showed an increased activity of both the acceptor and donor binding site of peptidyl transferase. In ribosomes from the tumor-host liver the activity of the acceptor site of this enzyme was decreased while that of the donor site remained unaltered. The enhanced activity of peptide elongation factor 1 from tumors and host liver is apparently the main reason of enhanced protein synthesis in these tissues. The enhanced activity of this factor is not specific for tumor growth as it occurs also in other pathological conditions.", "contents": "Protein synthesis in tumor host. II. Increased activity of peptide elongation factor 1 in experimental rat tumors and in host liver. Both peptide elongation factors were purified from Zajdela and Walker tumors and from the host and normal liver. The activity of peptide elongation factor 1 from tumor tissues in promoting the binding of phenylalanyl-tRNA to ribosomes was significantly higher than that of normal liver. Also preparations from the host liver were markedly more active when compared with the corresponding factor from normal liver. Poly(U)-dependent phenylalanine polymerization was enhanced in subcellular systems containing elongation factor 1 from tumors or host liver. No differences were found between preparations of elongation factor 2 isolated from various sources. Tumor ribosomes showed an increased activity of both the acceptor and donor binding site of peptidyl transferase. In ribosomes from the tumor-host liver the activity of the acceptor site of this enzyme was decreased while that of the donor site remained unaltered. The enhanced activity of peptide elongation factor 1 from tumors and host liver is apparently the main reason of enhanced protein synthesis in these tissues. The enhanced activity of this factor is not specific for tumor growth as it occurs also in other pathological conditions."}
{"id": "PMID:221849", "title": "Effects of superoxide radicals on transport (Na + K) adenosine triphosphatase and protection by superoxide dismutase.", "content": "Membrane (Na +K)ATPase isolated from rat brain was preincubated in a medium in which superoxide radicals were generated enzymatically. Exposure to superoxide radicals caused an irreversible inactivation, which could be prevented by further addition of superoxide dismutase. (Na + K)ATPase was also protected by addition of allopurinol, a xanthine oxidase inhibitor, during preincubation. The K-activated nitrophenylphosphatase associated with (Na + K)ATPase was also found to be inactivated by preincubation with superoxide radicals, which could be prevented by superoxide dismutase.", "contents": "Effects of superoxide radicals on transport (Na + K) adenosine triphosphatase and protection by superoxide dismutase. Membrane (Na +K)ATPase isolated from rat brain was preincubated in a medium in which superoxide radicals were generated enzymatically. Exposure to superoxide radicals caused an irreversible inactivation, which could be prevented by further addition of superoxide dismutase. (Na + K)ATPase was also protected by addition of allopurinol, a xanthine oxidase inhibitor, during preincubation. The K-activated nitrophenylphosphatase associated with (Na + K)ATPase was also found to be inactivated by preincubation with superoxide radicals, which could be prevented by superoxide dismutase."}
{"id": "PMID:221852", "title": "Nerve and muscle biopsy: electrophysiology and morphology in polyneuropathy.", "content": "We correlated the results of biopsy of a muscle nerve, a sensory nerve, and tibialis anterior muscle with electrophysiologic studies in 13 patients with sensorimotor polyneuropathy and 6 patients with normal findings. There were significant correlations between teased fiber changes and conduction abnormalities in both muscle nerves and sensory nerves. The density of large myelinated fibers in the lateral fascicle of the deep peroneal (LFDP) nerve correlated significantly with both the motor unit estimate and compound action potential amplitude of the extensor digitorum brevis (EDB) muscle. Other characteristics of the EDB muscle compound action potential related poorly to teased fiber abnormalities. There was good correlation of needle electrode study of the EDB muscle with teased fiber analysis of the LFDP nerve and with the morphology of the tibialis anterior muscle in 75 percent of the cases, and only minor discrepancies in the remainder. These results emphasize the close relationship between certain structural and electrophysiologic changes in subacute and chronic polyneuropathy.", "contents": "Nerve and muscle biopsy: electrophysiology and morphology in polyneuropathy. We correlated the results of biopsy of a muscle nerve, a sensory nerve, and tibialis anterior muscle with electrophysiologic studies in 13 patients with sensorimotor polyneuropathy and 6 patients with normal findings. There were significant correlations between teased fiber changes and conduction abnormalities in both muscle nerves and sensory nerves. The density of large myelinated fibers in the lateral fascicle of the deep peroneal (LFDP) nerve correlated significantly with both the motor unit estimate and compound action potential amplitude of the extensor digitorum brevis (EDB) muscle. Other characteristics of the EDB muscle compound action potential related poorly to teased fiber abnormalities. There was good correlation of needle electrode study of the EDB muscle with teased fiber analysis of the LFDP nerve and with the morphology of the tibialis anterior muscle in 75 percent of the cases, and only minor discrepancies in the remainder. These results emphasize the close relationship between certain structural and electrophysiologic changes in subacute and chronic polyneuropathy."}
{"id": "PMID:221850", "title": "[ABO blood groups in glioblastoma multiforme].", "content": "The distribution of ABO blood groups was analysed statistically in 271 patients treated for glioblastoma multiforme. The control group included 500 patients treated for craniocerebral trauma. A statistically significant difference was observed in the distribution of ABO blood groups between these patient groups, with higher frequency of group  A and lower of group O in the patients with glioblastoma multiforme.", "contents": "[ABO blood groups in glioblastoma multiforme]. The distribution of ABO blood groups was analysed statistically in 271 patients treated for glioblastoma multiforme. The control group included 500 patients treated for craniocerebral trauma. A statistically significant difference was observed in the distribution of ABO blood groups between these patient groups, with higher frequency of group  A and lower of group O in the patients with glioblastoma multiforme."}
{"id": "PMID:221853", "title": "Pontine infarction manifesting as isolated cranial nerve palsies.", "content": "Isolated ipsilateral fifth, seventh, tenth and twelfth cranial nerve palsies in a 74-year-old woman were shown at autopsy to result from an inferior lateral pontine infarction. The clinical features and pathogenesis of this uncommon lesion are discussed.", "contents": "Pontine infarction manifesting as isolated cranial nerve palsies. Isolated ipsilateral fifth, seventh, tenth and twelfth cranial nerve palsies in a 74-year-old woman were shown at autopsy to result from an inferior lateral pontine infarction. The clinical features and pathogenesis of this uncommon lesion are discussed."}
{"id": "PMID:221854", "title": "Neuromuscular defect after suppression of ion conductance.", "content": "In rat skeletal muscle, trimetazidine (TMZ) caused a transmission defect without directly blocking binding of acetylcholine--ionophore impairment. In vivo, TMZ produced low-amplitude and cumulative depression of successive muscle responses, and immediate posttetanic exhaustion. These features differed from the effects of alpha-bungarotoxin (alpha-BuTx) or immunization with acetylcholine receptor (experimental autoimmune myasthenia gravis [EAMG]). In vitro, TMZ-induced block was similar to both alpha-BuTx-induced block and EAMG in many respects, but there were differences in endplate potentials evoked during and after rapid repetitive activations. These differences suggest that antibodies to the acetylcholine receptor do not affect the ionophore.", "contents": "Neuromuscular defect after suppression of ion conductance. In rat skeletal muscle, trimetazidine (TMZ) caused a transmission defect without directly blocking binding of acetylcholine--ionophore impairment. In vivo, TMZ produced low-amplitude and cumulative depression of successive muscle responses, and immediate posttetanic exhaustion. These features differed from the effects of alpha-bungarotoxin (alpha-BuTx) or immunization with acetylcholine receptor (experimental autoimmune myasthenia gravis [EAMG]). In vitro, TMZ-induced block was similar to both alpha-BuTx-induced block and EAMG in many respects, but there were differences in endplate potentials evoked during and after rapid repetitive activations. These differences suggest that antibodies to the acetylcholine receptor do not affect the ionophore."}
{"id": "PMID:221855", "title": "Myotonic muscular dystrophy: abnormal temperature response of membrane phosphorylation in erythrocyte membranes.", "content": "The activities of the membrane-bound protein kinases of the human erythrocytes membrane that phosphorylate spectrin, band-3 protein, and phospholipids were compared in patients with myotonic muscular dystrophy and normal age- and sex-matched controls. These activities tended to be lower in the patients, but the differences were not statistically significant. In contrast, the temperature responses (the increase in activity in response to an increase in temperature from 30 degrees C to 37 degrees C) of the spectrin and band-3 protein kinase activities were significantly lower in the patients. Although they do not eliminate an alteration of one of the substrates, these results are consistent with the proposal that differences in erythrocytes from myotonic muscular dystrophy (MyD) patients are due to a membrane lipid change. Cholesterol is unlikely to be the altered lipid, as no difference in membrane cholesterol content was found.", "contents": "Myotonic muscular dystrophy: abnormal temperature response of membrane phosphorylation in erythrocyte membranes. The activities of the membrane-bound protein kinases of the human erythrocytes membrane that phosphorylate spectrin, band-3 protein, and phospholipids were compared in patients with myotonic muscular dystrophy and normal age- and sex-matched controls. These activities tended to be lower in the patients, but the differences were not statistically significant. In contrast, the temperature responses (the increase in activity in response to an increase in temperature from 30 degrees C to 37 degrees C) of the spectrin and band-3 protein kinase activities were significantly lower in the patients. Although they do not eliminate an alteration of one of the substrates, these results are consistent with the proposal that differences in erythrocytes from myotonic muscular dystrophy (MyD) patients are due to a membrane lipid change. Cholesterol is unlikely to be the altered lipid, as no difference in membrane cholesterol content was found."}
{"id": "PMID:221856", "title": "Hoquet diabolique: intractable hiccups as a manifestation of multiple sclerosis.", "content": "In three patients, intractable hiccups occurred as part of the symptomatology of multiple sclerosis. In one patient intractable hiccups were the presenting complaint, and in another patient exacerbations of symptoms were almost always heralded by intractable hiccups. Intractable hiccups occur in a variety of diseases, including many that affect the brainstem and cervical cord, but have not been reported in multiple sclerosis. The hiccup may be a \"primitive\" gastrointestinal reflex that is disinhibited by lesions such as multiple sclerosis plaques. Carbamazepine was successful in arresting the hiccups in one of the cases presented.", "contents": "Hoquet diabolique: intractable hiccups as a manifestation of multiple sclerosis. In three patients, intractable hiccups occurred as part of the symptomatology of multiple sclerosis. In one patient intractable hiccups were the presenting complaint, and in another patient exacerbations of symptoms were almost always heralded by intractable hiccups. Intractable hiccups occur in a variety of diseases, including many that affect the brainstem and cervical cord, but have not been reported in multiple sclerosis. The hiccup may be a \"primitive\" gastrointestinal reflex that is disinhibited by lesions such as multiple sclerosis plaques. Carbamazepine was successful in arresting the hiccups in one of the cases presented."}
{"id": "PMID:221857", "title": "Friedreich ataxia. II. Normal kinetics of lipoamide dehydrogenase.", "content": "Lipoamide dehydrogenase (LAD) kinetic values, Km and Vmax, were normal in 11 patients with Friedreich ataxia. Fibroblast activities of the pyruvate and alpha-ketoglutarate dehydrogenase complex, and LAD activities, were also normal. There was no reduction in oxidative decarboxylation of pyruvate, alpha-ketoglutarate, or several other substrates in intact fibroblasts. Methodologic differences may account for differences of opinion about putative abnormalities of the alpha-ketoacid dehydrogenase complexes.", "contents": "Friedreich ataxia. II. Normal kinetics of lipoamide dehydrogenase. Lipoamide dehydrogenase (LAD) kinetic values, Km and Vmax, were normal in 11 patients with Friedreich ataxia. Fibroblast activities of the pyruvate and alpha-ketoglutarate dehydrogenase complex, and LAD activities, were also normal. There was no reduction in oxidative decarboxylation of pyruvate, alpha-ketoglutarate, or several other substrates in intact fibroblasts. Methodologic differences may account for differences of opinion about putative abnormalities of the alpha-ketoacid dehydrogenase complexes."}
{"id": "PMID:221858", "title": "Peripheral neuropathy in cerebrotendinous xanthomatosis.", "content": "Four patients with cerebrotendinous xanthomatosis (CTX) underwent electrophysiologic investigations, which demonstrated impairment in the functioning of the peripheral nerves in all four cases. The changes consisted of slow motor and sensory conduction. The changes were most marked in the older subjects, in whom the disease was more advanced, and who also had clinical manifestations of mild peripheral neuropathy. We conclude that the peripheral nerves are damaged in CTX.", "contents": "Peripheral neuropathy in cerebrotendinous xanthomatosis. Four patients with cerebrotendinous xanthomatosis (CTX) underwent electrophysiologic investigations, which demonstrated impairment in the functioning of the peripheral nerves in all four cases. The changes consisted of slow motor and sensory conduction. The changes were most marked in the older subjects, in whom the disease was more advanced, and who also had clinical manifestations of mild peripheral neuropathy. We conclude that the peripheral nerves are damaged in CTX."}
{"id": "PMID:221859", "title": "Fabry disease: cellular expression of enzyme deficiency in nerve xenografts.", "content": "Human sural nerve fascicles from a patient with Fabry disease were transplanted into nude-mouse sciatic nerves to determine whether transplanted perineurial cells and smooth-muscle cells of an epineurial artery would express the genetic abnormality of the disease. Four months after grafting, both perineurial cells and smooth-muscle cells contained the cytoplasmic lamellated inclusion bodies characteristic of Fabry disease. This provided evidence of human perineurial cells and smooth-muscle cells in the regenerated xenografts.", "contents": "Fabry disease: cellular expression of enzyme deficiency in nerve xenografts. Human sural nerve fascicles from a patient with Fabry disease were transplanted into nude-mouse sciatic nerves to determine whether transplanted perineurial cells and smooth-muscle cells of an epineurial artery would express the genetic abnormality of the disease. Four months after grafting, both perineurial cells and smooth-muscle cells contained the cytoplasmic lamellated inclusion bodies characteristic of Fabry disease. This provided evidence of human perineurial cells and smooth-muscle cells in the regenerated xenografts."}
{"id": "PMID:221871", "title": "Estrogen replacement therapy II: a prospective study in the relationship to carcinoma and cardiovascular and metabolic problems.", "content": "A 10-year double-blind prospective study was undertaken to evaluate the effects of estrogen replacement therapy (ERT). The sample population consisted of 84 pairs of randomly chosen postmenopausal in-patients, matched for age and diagnosis. The treatment group received high-dose conjugated estrogens, cyclically with progesterone. The controls recieved placebos. Results revealed no statistically significant difference in that incidence of thrombophlebitis, myocardial infarction (MI), or uterine cancer. There was a lower incidence of breast cancer in the treated group. Estrogen-treated patients showed a higher incidence of cholelithiasis. Those in the treated group who began the study with elevated beta/alpha lipoprotein ratios showed a reduction in that ratio over the course of the study, while the controls either maintained or increased their ratios. The low number of cases precludes drawing any real significance from the data on diseases of low frequency. The study excludes only a high incidence of complications from estrogens.", "contents": "Estrogen replacement therapy II: a prospective study in the relationship to carcinoma and cardiovascular and metabolic problems. A 10-year double-blind prospective study was undertaken to evaluate the effects of estrogen replacement therapy (ERT). The sample population consisted of 84 pairs of randomly chosen postmenopausal in-patients, matched for age and diagnosis. The treatment group received high-dose conjugated estrogens, cyclically with progesterone. The controls recieved placebos. Results revealed no statistically significant difference in that incidence of thrombophlebitis, myocardial infarction (MI), or uterine cancer. There was a lower incidence of breast cancer in the treated group. Estrogen-treated patients showed a higher incidence of cholelithiasis. Those in the treated group who began the study with elevated beta/alpha lipoprotein ratios showed a reduction in that ratio over the course of the study, while the controls either maintained or increased their ratios. The low number of cases precludes drawing any real significance from the data on diseases of low frequency. The study excludes only a high incidence of complications from estrogens."}
{"id": "PMID:221872", "title": "Serum lipids in hepatoma.", "content": "Serum lipids were determined in patients with hepatoma, liver cirrhosis and healthy controls. Serum total cholesterol, esterified cholesterol, triglycerides, and phospholipid were increased in cases with hepatoma compared to those with cirrhosis, irrespective of a history of liver cirrhosis in the hepatome group of patients. From this study one can conclude that the determination of serum lipids is useful in differentiating carcinoma from liver cirrhosis. This may be used as a tool for the early detection of hepatoma complicating liver cirrhosis.", "contents": "Serum lipids in hepatoma. Serum lipids were determined in patients with hepatoma, liver cirrhosis and healthy controls. Serum total cholesterol, esterified cholesterol, triglycerides, and phospholipid were increased in cases with hepatoma compared to those with cirrhosis, irrespective of a history of liver cirrhosis in the hepatome group of patients. From this study one can conclude that the determination of serum lipids is useful in differentiating carcinoma from liver cirrhosis. This may be used as a tool for the early detection of hepatoma complicating liver cirrhosis."}
{"id": "PMID:221874", "title": "Calcium, phosphate, and vitamin D.", "content": "It is evident that there has been enormous progress within the last decade in our understanding of vitamin D metabolism and its interaction with calcium, phosphate, parathyroid hormone, and a number of other factors. As a result largely of therapeutic trials with various metabolites of vitamin D, we now know something of their probable involvement in the development of rickets and osteomalacia. We do not yet have a clear comprehension of exactly how these metabolites influence bone mineralization other than through their indirect effect on serum calcium and phosphate. Nonetheless it seems likely that at least one, and perhaps more, of the metabolites do exert a more direct effect. One must conclude that a deficiency of the 1alpha-hydroxylase is probably not the only defect in renal insufficiency, although it currently that there must well known. It is premature to go so far as to suggest that there must be another metabolite not being synthesized in the diseased or absent kidney.", "contents": "Calcium, phosphate, and vitamin D. It is evident that there has been enormous progress within the last decade in our understanding of vitamin D metabolism and its interaction with calcium, phosphate, parathyroid hormone, and a number of other factors. As a result largely of therapeutic trials with various metabolites of vitamin D, we now know something of their probable involvement in the development of rickets and osteomalacia. We do not yet have a clear comprehension of exactly how these metabolites influence bone mineralization other than through their indirect effect on serum calcium and phosphate. Nonetheless it seems likely that at least one, and perhaps more, of the metabolites do exert a more direct effect. One must conclude that a deficiency of the 1alpha-hydroxylase is probably not the only defect in renal insufficiency, although it currently that there must well known. It is premature to go so far as to suggest that there must be another metabolite not being synthesized in the diseased or absent kidney."}
{"id": "PMID:221875", "title": "The non-ossified pubis.", "content": "A group of syndromes is presented whose common characteristic is the absence of pubic ossification at birth with very slow posterior mineralization. This is a radiological finding of interest as it has not been described in other entities. In all the cases shown, moreover, a variable degree of delay in bone age is observed. The increase of space between the pubic bones described in these syndromes is fictious, as it really signifies the existence of non-ossified cartilage. Therefore, they must be differentiated from those which deal with real widening of the symphysis of pubis.", "contents": "The non-ossified pubis. A group of syndromes is presented whose common characteristic is the absence of pubic ossification at birth with very slow posterior mineralization. This is a radiological finding of interest as it has not been described in other entities. In all the cases shown, moreover, a variable degree of delay in bone age is observed. The increase of space between the pubic bones described in these syndromes is fictious, as it really signifies the existence of non-ossified cartilage. Therefore, they must be differentiated from those which deal with real widening of the symphysis of pubis."}
{"id": "PMID:221877", "title": "Chronic diarrhea of infancy: nonbeta islet cell hyperplasia.", "content": "The case of an infant who developed refractory watery diarrhea at the age of 2 weeks is described. Diarrhea was secretory in type, stool weight on no oral intake was 400 to 600 gm daily. A vasoactive intestinal peptide (VIP)-producing tumor was suspected. At the age of 7 1/2 months an exploratory laparotomy revealed nonbeta islet cell hyperplasia of the pancreas. VIP levels were elevated in plasma and pancreatic tissue. After 95% pancreatectomy, plasma VIP level dropped to normal. Hypokalemia, described in adult patients with VIP-producing pancreatic tumors and refractory watery diarrhea, was not a significant problem in this infant. This is the first report on the association of refractory watery diarrhea with elevated levels of plasma VIP and pancreatic islet nonbeta cell hyperplasia in the pediatric age group.", "contents": "Chronic diarrhea of infancy: nonbeta islet cell hyperplasia. The case of an infant who developed refractory watery diarrhea at the age of 2 weeks is described. Diarrhea was secretory in type, stool weight on no oral intake was 400 to 600 gm daily. A vasoactive intestinal peptide (VIP)-producing tumor was suspected. At the age of 7 1/2 months an exploratory laparotomy revealed nonbeta islet cell hyperplasia of the pancreas. VIP levels were elevated in plasma and pancreatic tissue. After 95% pancreatectomy, plasma VIP level dropped to normal. Hypokalemia, described in adult patients with VIP-producing pancreatic tumors and refractory watery diarrhea, was not a significant problem in this infant. This is the first report on the association of refractory watery diarrhea with elevated levels of plasma VIP and pancreatic islet nonbeta cell hyperplasia in the pediatric age group."}
{"id": "PMID:221878", "title": "REM need in adolescents as indicated by resistance to REM deprivation.", "content": "The hypothesis that adolescents have an exceptionally strong need for REM sleep was tested by measuring their resistance to REM deprivation. Ten adolescents (aged 16 to 17 yr.) were compared with 12 young adults (aged 25 to 27 yr.) in a standard REM deprivation procedure. The adolescents had to be awakened significantly more times than the young adults; this is consistent with the hypothesis that adolescents have a greater need for REM sleep.", "contents": "REM need in adolescents as indicated by resistance to REM deprivation. The hypothesis that adolescents have an exceptionally strong need for REM sleep was tested by measuring their resistance to REM deprivation. Ten adolescents (aged 16 to 17 yr.) were compared with 12 young adults (aged 25 to 27 yr.) in a standard REM deprivation procedure. The adolescents had to be awakened significantly more times than the young adults; this is consistent with the hypothesis that adolescents have a greater need for REM sleep."}
{"id": "PMID:221879", "title": "Activation of membrane Na+/K+-ATPase of mouse skeletal muscle by acetylcholine and its inhibition by alpha-bungarotoxin, curare and atropine.", "content": "The effect of acetylcholine and of three cholinolytic compounds (alpha-bungarotoxin, curare and atropine) on electrogenic Na+/K+ pump and activity of the membrane Na+/K+-ATPase of mouse skeletal muscles was studied. It was found that acetylcholine potentiated both the muscle electrogenic ionic pump and the Na+/K+-ATPase activity of crude membrane fractions. The cholinolytic drugs had inhibitory effects on both parameters, with the exception of curare which was ineffective in blocking the electrogenic ionic pump.", "contents": "Activation of membrane Na+/K+-ATPase of mouse skeletal muscle by acetylcholine and its inhibition by alpha-bungarotoxin, curare and atropine. The effect of acetylcholine and of three cholinolytic compounds (alpha-bungarotoxin, curare and atropine) on electrogenic Na+/K+ pump and activity of the membrane Na+/K+-ATPase of mouse skeletal muscles was studied. It was found that acetylcholine potentiated both the muscle electrogenic ionic pump and the Na+/K+-ATPase activity of crude membrane fractions. The cholinolytic drugs had inhibitory effects on both parameters, with the exception of curare which was ineffective in blocking the electrogenic ionic pump."}
{"id": "PMID:221880", "title": "[Type V hyperlipemia. 54 cases (author's transl)].", "content": "Type V hyperlipemia is not very common. The series of 54 cases descrubed here is the largest reported to date. Our observations were recorded when lipidograms showed the presence of chylomicrons and a large pre-beta-lipoprotein spot in the serum of fasting subjects. Type V hyperlipemia was often combined with other metabolic syndromes such as diabetes, hyperuricemia or gout, or obesity. Chronic alcoholism was also noted in half our subjects, in whom hyperlipemia quickly regressed after alcohol consumption ceased. Ischemic arterial complications, chiefly coronary, were found in one third of our cases, and the vascular risks accompanying this type of hyperlipemia rose considerably in patients with high blood pressure. Various type of treatment were administered, but all subjects were put on a special diet, comprising either the elimination of alcoholic drinks only, or, in addition to this, reduced carbohydrate or calorie intake. As a rule, these measures resulted in a distinct regression of lipid anomalies. Clofibrate or derivatives proved effective in cases where hyperlipemia failed to respond to dietary measures.", "contents": "[Type V hyperlipemia. 54 cases (author's transl)]. Type V hyperlipemia is not very common. The series of 54 cases descrubed here is the largest reported to date. Our observations were recorded when lipidograms showed the presence of chylomicrons and a large pre-beta-lipoprotein spot in the serum of fasting subjects. Type V hyperlipemia was often combined with other metabolic syndromes such as diabetes, hyperuricemia or gout, or obesity. Chronic alcoholism was also noted in half our subjects, in whom hyperlipemia quickly regressed after alcohol consumption ceased. Ischemic arterial complications, chiefly coronary, were found in one third of our cases, and the vascular risks accompanying this type of hyperlipemia rose considerably in patients with high blood pressure. Various type of treatment were administered, but all subjects were put on a special diet, comprising either the elimination of alcoholic drinks only, or, in addition to this, reduced carbohydrate or calorie intake. As a rule, these measures resulted in a distinct regression of lipid anomalies. Clofibrate or derivatives proved effective in cases where hyperlipemia failed to respond to dietary measures."}
{"id": "PMID:221881", "title": "[The treatment of organic pain of the peripheral nervous system using clomipramine. 30 cases (author's transl)].", "content": "Clomipramine used alone is an affective analgesic against organic pain due to a lesion of the peripheral nervous system, in particular post-herpetic pain. The quality of the result is related to the dose, and hence to tolerance. Fluohydrocortisone is the most powerful drug against orthostatic hypotension, the chief cause of limitation of treatment. No complications were seen, even in very elderly patients.", "contents": "[The treatment of organic pain of the peripheral nervous system using clomipramine. 30 cases (author's transl)]. Clomipramine used alone is an affective analgesic against organic pain due to a lesion of the peripheral nervous system, in particular post-herpetic pain. The quality of the result is related to the dose, and hence to tolerance. Fluohydrocortisone is the most powerful drug against orthostatic hypotension, the chief cause of limitation of treatment. No complications were seen, even in very elderly patients."}
{"id": "PMID:221882", "title": "[Hepatitis A of children. Seroepidemiological study among French urban population (author's transl)].", "content": "A prevalence survey of hepatitis A antibody (anti-HAV) was conducted among 145 children living in the area of Tours (France). Thirty-four per cent of children's sera was found anti-HAV positive when tested by both immune adherence hemagglutination assay (IAHA) and specific radio-immunoassay (RIA). The prevalence of anti-HAV among infants less than one year and children between 1 to 5 years, was 35 per cent and 15 per cent respectively. From 6 years old, the prevalence of anti-HAV increased abruptly and reached 47 per cent in the 11 to 15 age group. Anti-HAV titers as measured by IAHA also increased according to age. In this study, the prevalence of anti-HAV was not related to sex, history of past surgery and/or blood transfusions. Only 12 per cent of children with anti-HAV positive test had history of jaundice. These results show that, in France, primary contact with hepatitis A virus (HAV) appear early in childhood, at school age, and that in children more than 80% of HAV infections remain asymptomatic.", "contents": "[Hepatitis A of children. Seroepidemiological study among French urban population (author's transl)]. A prevalence survey of hepatitis A antibody (anti-HAV) was conducted among 145 children living in the area of Tours (France). Thirty-four per cent of children's sera was found anti-HAV positive when tested by both immune adherence hemagglutination assay (IAHA) and specific radio-immunoassay (RIA). The prevalence of anti-HAV among infants less than one year and children between 1 to 5 years, was 35 per cent and 15 per cent respectively. From 6 years old, the prevalence of anti-HAV increased abruptly and reached 47 per cent in the 11 to 15 age group. Anti-HAV titers as measured by IAHA also increased according to age. In this study, the prevalence of anti-HAV was not related to sex, history of past surgery and/or blood transfusions. Only 12 per cent of children with anti-HAV positive test had history of jaundice. These results show that, in France, primary contact with hepatitis A virus (HAV) appear early in childhood, at school age, and that in children more than 80% of HAV infections remain asymptomatic."}
{"id": "PMID:221883", "title": "[Primary empty sella associated with peripheral endocrine deficiency: two cases (author's transl)].", "content": "The radiological finding of a large sella turcica in long standing peripheral endocrine insufficiency (adrenocortical in one case, thyroid in the other) and the persistence of plasma ACTH and TSH levels above normal despite hormone therapy was first attributed to the consequences of reactive hypersecretion of the corresponding stimulin. The results of scanner studies in one case, and of pathological examination in the other, revealed the presence of primary empty sella syndrom.", "contents": "[Primary empty sella associated with peripheral endocrine deficiency: two cases (author's transl)]. The radiological finding of a large sella turcica in long standing peripheral endocrine insufficiency (adrenocortical in one case, thyroid in the other) and the persistence of plasma ACTH and TSH levels above normal despite hormone therapy was first attributed to the consequences of reactive hypersecretion of the corresponding stimulin. The results of scanner studies in one case, and of pathological examination in the other, revealed the presence of primary empty sella syndrom."}
{"id": "PMID:221885", "title": "[The prevention of chickenpox in high risk children. Comparison of the effectiveness of specific immunoglobulins and of defibrinated convalescent plasma. 414 cases (author's transl)].", "content": "Comparison between 157 children treated with defibrinated convalescent plasma and 257 children treated with specific immunoglobulins revealed the improved effectiveness of the latter treatment in the prevention of chickenpox. Specific Herpes Zoster-Chickenpox immunoglobulins are prepared by caprylic acid fractionation of convalescent plasma. The prevention obtained in more than 90% of cases would appear to be clinically and biologically total as shown by serological surveillance of certain children with particularly severe immune depression.", "contents": "[The prevention of chickenpox in high risk children. Comparison of the effectiveness of specific immunoglobulins and of defibrinated convalescent plasma. 414 cases (author's transl)]. Comparison between 157 children treated with defibrinated convalescent plasma and 257 children treated with specific immunoglobulins revealed the improved effectiveness of the latter treatment in the prevention of chickenpox. Specific Herpes Zoster-Chickenpox immunoglobulins are prepared by caprylic acid fractionation of convalescent plasma. The prevention obtained in more than 90% of cases would appear to be clinically and biologically total as shown by serological surveillance of certain children with particularly severe immune depression."}
{"id": "PMID:221886", "title": "Origin of two different classes of defective HSV-1 Angelotti DNA.", "content": "During serial passages of Herpes simplex virus (HSV) at high multiplicity of infection, virions containing defective viral DNA accumulate in the progeny. The defective DNA molecules are made up by repeats of restricted portions of the standard viral genome. Two different classes of defective DNA derived from HSV-1 Angelotti (ANG) in independent series of high MOI-passages were studied. The nucleotide sequences contained in the defective DNA were localized on the parental viral genome. One of the two classes contained sequences from non-contiguous sites mapping in unique and in redundant regions of the parental DNA, whereas the second class apparently originates from the S-terminal redundant region of the parental DNA. The localization of defective DNA sequences was complicated by the fact that there exists sequence homology between the S-terminal redundancy and various unique DNA sequences in the L-segment of the HSV-1 ANG genome.", "contents": "Origin of two different classes of defective HSV-1 Angelotti DNA. During serial passages of Herpes simplex virus (HSV) at high multiplicity of infection, virions containing defective viral DNA accumulate in the progeny. The defective DNA molecules are made up by repeats of restricted portions of the standard viral genome. Two different classes of defective DNA derived from HSV-1 Angelotti (ANG) in independent series of high MOI-passages were studied. The nucleotide sequences contained in the defective DNA were localized on the parental viral genome. One of the two classes contained sequences from non-contiguous sites mapping in unique and in redundant regions of the parental DNA, whereas the second class apparently originates from the S-terminal redundant region of the parental DNA. The localization of defective DNA sequences was complicated by the fact that there exists sequence homology between the S-terminal redundancy and various unique DNA sequences in the L-segment of the HSV-1 ANG genome."}
{"id": "PMID:221887", "title": "A possible mechanism responsible for the correction of transcription errors.", "content": "Nucleoside triphosphate phosphohydrolase (NTPase) activity was found in a preparation of E. Coli RNA polymerase. This enzymatic activity is capable of hydrolysing all four ribonucleoside triphosphates to the nucleoside diphosphates. However, during in vitro RNA synthesis directed by poly(dC) or poly(dT), only the non-complementary nucleoside triphosphate of the same heterocyclic class was hydrolysed. No incorporation of the non-complementary precursor into RNA could be detected in these experiments. When another RNA polymerase preparation, devoid of NTPase activity, was employed, there was no hydrolysis of any nucleoside triphosphate and significant incorporation of non-complemtary precursor into RNA was observed. These observations lead us to the conclusion that NTPase, acting in conjunction with RNA polymerase, has the function of correcting errors in transcription.", "contents": "A possible mechanism responsible for the correction of transcription errors. Nucleoside triphosphate phosphohydrolase (NTPase) activity was found in a preparation of E. Coli RNA polymerase. This enzymatic activity is capable of hydrolysing all four ribonucleoside triphosphates to the nucleoside diphosphates. However, during in vitro RNA synthesis directed by poly(dC) or poly(dT), only the non-complementary nucleoside triphosphate of the same heterocyclic class was hydrolysed. No incorporation of the non-complementary precursor into RNA could be detected in these experiments. When another RNA polymerase preparation, devoid of NTPase activity, was employed, there was no hydrolysis of any nucleoside triphosphate and significant incorporation of non-complemtary precursor into RNA was observed. These observations lead us to the conclusion that NTPase, acting in conjunction with RNA polymerase, has the function of correcting errors in transcription."}
{"id": "PMID:221888", "title": "Protected deoxyribonucleoside-3' aryl phosphodiesters as key intermediates in polynucleotide synthesis. Construction of an icosanucleotide analogous to the sequence at the ends of Rous sarcoma virus 35S RNA.", "content": "Several modifications have been incorporated into the phosphotriester strategy for chemical synthesis of oligodeoxyribonucleotides. These include high-yield methods of preparation and isolation of O5', N-protected deoxyribonucleoside-3' p-chlorophenyl phosphates which serve as key intermediates, and the elimination of some superfluous manipulation and purification steps commonly used in the process of synthesizing oligonucleotide blocks. In addition, two new arylsulfonyl nitroimidazole derivatives have been prepared and found to be highly effective agents for internucleotide bond formation. These techniques have been applied in construction of the iconsamer d(G-C-C-A-T-T-T-T-A-C-C-A-T-T-C-A-C-C-A)-rC, equivalent to a ribonucleotide sequence located at both the 5' and 3' ends of Rous sarcoma virus 35S RNA.", "contents": "Protected deoxyribonucleoside-3' aryl phosphodiesters as key intermediates in polynucleotide synthesis. Construction of an icosanucleotide analogous to the sequence at the ends of Rous sarcoma virus 35S RNA. Several modifications have been incorporated into the phosphotriester strategy for chemical synthesis of oligodeoxyribonucleotides. These include high-yield methods of preparation and isolation of O5', N-protected deoxyribonucleoside-3' p-chlorophenyl phosphates which serve as key intermediates, and the elimination of some superfluous manipulation and purification steps commonly used in the process of synthesizing oligonucleotide blocks. In addition, two new arylsulfonyl nitroimidazole derivatives have been prepared and found to be highly effective agents for internucleotide bond formation. These techniques have been applied in construction of the iconsamer d(G-C-C-A-T-T-T-T-A-C-C-A-T-T-C-A-C-C-A)-rC, equivalent to a ribonucleotide sequence located at both the 5' and 3' ends of Rous sarcoma virus 35S RNA."}
{"id": "PMID:221889", "title": "Expression of single copy DNA sequences in nuclear RNA from undifferentiated mouse embryonal carcinoma and differentiated muscle cell line.", "content": "Nuclear RNA from an undifferentiated mouse embryonal carcionma (EC) cell line and a differentiated muscle (Mt) cell line from similar origin has been analysed with respect to base sequence complexity and frequency distribution with different probes. With the single copy component of mouse genomic DNA it is shown that total EC nuclear RNA and Mt nuclear RNA have respectively base sequence complexities of 100 Kb and 140 Kb corresponding to 6% and 8% of one strand of DNA. It is shown by hybridization with a purified DNA component complementary to total nuclear RNA that nuclear poly A+RNA in both cell types has only one fifth of total nuclear RNA complexity (as has polysomal RNA), but still contains all poly A+RNA present in polysomal poly A+RNA. Polysomal poly A+ sequences in total and poly A+ nuclear RNA are present in a restricted range of frequency distribution in contrast to the situation observed at the polysomal level. The implication of these results in terms of transcriptional and post-transcriptional control is discussed.", "contents": "Expression of single copy DNA sequences in nuclear RNA from undifferentiated mouse embryonal carcinoma and differentiated muscle cell line. Nuclear RNA from an undifferentiated mouse embryonal carcionma (EC) cell line and a differentiated muscle (Mt) cell line from similar origin has been analysed with respect to base sequence complexity and frequency distribution with different probes. With the single copy component of mouse genomic DNA it is shown that total EC nuclear RNA and Mt nuclear RNA have respectively base sequence complexities of 100 Kb and 140 Kb corresponding to 6% and 8% of one strand of DNA. It is shown by hybridization with a purified DNA component complementary to total nuclear RNA that nuclear poly A+RNA in both cell types has only one fifth of total nuclear RNA complexity (as has polysomal RNA), but still contains all poly A+RNA present in polysomal poly A+RNA. Polysomal poly A+ sequences in total and poly A+ nuclear RNA are present in a restricted range of frequency distribution in contrast to the situation observed at the polysomal level. The implication of these results in terms of transcriptional and post-transcriptional control is discussed."}
{"id": "PMID:221890", "title": "Genome organization of retroviruses. III. Restriction endonuclease cleavage maps of mouse sarcoma virus double-stranded DNA synthesized in vitro.", "content": "Genome length complementary DNA (cDNA) transcripts were synthesized in vitro by using purified virions of a cloned isolate of mouse sarcoma virus (MSV Clone 124). The cDNA transcripts were converted to double-stranded form by utilizing DNase-digested calf thymus DNA primers and E. coli DNA polymerase I. Restriction endonucleases Sal I, Hind III, Hpa I, Bgl II and Xba I were found to cleave the MSV double-stranded DNA once to generate two fragments, whereas restriction endonucleases Bgl I and Hae II cleaved twice to generate three fragments. Restriction endonucleases E. coli RI and Bam HI did not cleave MSV double-stranded DNA. The order of the restriction fragments was determined in relation to the 5' and 3' ends of the genomic RNA.", "contents": "Genome organization of retroviruses. III. Restriction endonuclease cleavage maps of mouse sarcoma virus double-stranded DNA synthesized in vitro. Genome length complementary DNA (cDNA) transcripts were synthesized in vitro by using purified virions of a cloned isolate of mouse sarcoma virus (MSV Clone 124). The cDNA transcripts were converted to double-stranded form by utilizing DNase-digested calf thymus DNA primers and E. coli DNA polymerase I. Restriction endonucleases Sal I, Hind III, Hpa I, Bgl II and Xba I were found to cleave the MSV double-stranded DNA once to generate two fragments, whereas restriction endonucleases Bgl I and Hae II cleaved twice to generate three fragments. Restriction endonucleases E. coli RI and Bam HI did not cleave MSV double-stranded DNA. The order of the restriction fragments was determined in relation to the 5' and 3' ends of the genomic RNA."}
{"id": "PMID:221897", "title": "Specificity of memory cells raised against trinitrophenyl-conjugated syngeneic cells.", "content": "Exogenous lipid analogues can be incorporated into purified plasma membranes of EL4 tumor cells. When EL4 membranes are incubated with sonicated lipid vesicles containing spin-labeled phosphatidylcholine and then purified, they exhibit paramagnetic resonance spectra characteristic of spin labels dilutely dispersed in the lipid bilayer. Also, when EL4 membranes are incubated with vesicles of fluorescent lipid (N-4-nitrobenzo-2-oxa-1,3-diazole phosphatidylethanolamine), the fluorescence intensity of the mixture gradually increases and the labeled membranes are strongly fluorescent under a microscope, whereas the original lipid vesicles are much less fluorescent because of self-quenching at the high relative concentration of the fluorophore in the vesicles (33%, wt/wt). Thus, lipid analogues can be integrated into the bilayers of EL4 plasma membranes. The ability of the EL4 membranes containing trinitrophenyl phosphatidylethanolamine to induce a secondary proliferation of C57BL/6 mouse spleen lymphocytes primarily stimulated by trinitrophenyl-modified autologous cells was investigated. Although trinitrophenyl-modified plasma membranes as well as trinitrophenyl-modified lymphocytes or EL4 cells caused a specific, H-2 restricted response, membranes containing trinitrophenyl phosphatidylethanolamine did not induce a secondary proliferative response. Because of the strong likelihood that all three lipid analogues mentioned above are similar to one another in having a high lateral mobility and in not being strongly associated with H-2 cell-surface molecules, these results can be viewed, with caution, as being consistent with a \"modified self\" model rather than a dual recognition model for H-2 restriction in the cell-mediated immune response to chemically modified syngeneic cells.", "contents": "Specificity of memory cells raised against trinitrophenyl-conjugated syngeneic cells. Exogenous lipid analogues can be incorporated into purified plasma membranes of EL4 tumor cells. When EL4 membranes are incubated with sonicated lipid vesicles containing spin-labeled phosphatidylcholine and then purified, they exhibit paramagnetic resonance spectra characteristic of spin labels dilutely dispersed in the lipid bilayer. Also, when EL4 membranes are incubated with vesicles of fluorescent lipid (N-4-nitrobenzo-2-oxa-1,3-diazole phosphatidylethanolamine), the fluorescence intensity of the mixture gradually increases and the labeled membranes are strongly fluorescent under a microscope, whereas the original lipid vesicles are much less fluorescent because of self-quenching at the high relative concentration of the fluorophore in the vesicles (33%, wt/wt). Thus, lipid analogues can be integrated into the bilayers of EL4 plasma membranes. The ability of the EL4 membranes containing trinitrophenyl phosphatidylethanolamine to induce a secondary proliferation of C57BL/6 mouse spleen lymphocytes primarily stimulated by trinitrophenyl-modified autologous cells was investigated. Although trinitrophenyl-modified plasma membranes as well as trinitrophenyl-modified lymphocytes or EL4 cells caused a specific, H-2 restricted response, membranes containing trinitrophenyl phosphatidylethanolamine did not induce a secondary proliferative response. Because of the strong likelihood that all three lipid analogues mentioned above are similar to one another in having a high lateral mobility and in not being strongly associated with H-2 cell-surface molecules, these results can be viewed, with caution, as being consistent with a \"modified self\" model rather than a dual recognition model for H-2 restriction in the cell-mediated immune response to chemically modified syngeneic cells."}
{"id": "PMID:221898", "title": "Hormonally specific expression of cardiac protein kinase activity.", "content": "The relationship between the effects of isoproterenol and prostaglandin E(1) (PGE(1)) on contractile state, cyclic AMP accumulation, and the activation states of protein kinase (ATP: protein phosphotransferase, EC 2.7.1.37), phosphorylase kinase, glycogen synthase, and glycogen phosphorylase have been studied in the isolated perfused rat heart. Perfusion of hearts with isoproterenol (10 or 80 nM) caused enhancement of left ventricular dP/dt (P, pressure), increased intracellular cyclic AMP, increased the activation states of protein kinase, phosphorylase kinase, glycogen phosphorylase, and conversion of glycogen synthase to a less active form. PGE(1) (2 or 30 muM) increased cyclic AMP accumulation and activated protein kinase, but caused no detectable changes in dP/dt or the activation states of the protein kinase substrates involved in glycogen metabolism. Perfusion of hearts with either 10 nM isoproterenol or 30 muM PGE(1) produced comparable increases in cyclic AMP accumulation and protein kinase activity. Exposure of hearts to a combination of these agents caused additive effects on cyclic AMP content and protein kinase activity. However, values for phosphorylase kinase, glycogen phosphorylase, glycogen synthase, and dP/dt did not differ from those observed in the presence of 10 nM isoproterenol alone. The failure of PGE(1) to stimulate phosphorylation of protein kinase substrates was not due to an increase in phosphorylase phosphatase activity. We conclude that an increase in intracellular cyclic AMP and the subsequent activation of protein kinase are insufficient to change either the activities of phosphorylase kinase, glycogen phosphorylase, and glycogen synthase or the inotropic state of heart muscle.", "contents": "Hormonally specific expression of cardiac protein kinase activity. The relationship between the effects of isoproterenol and prostaglandin E(1) (PGE(1)) on contractile state, cyclic AMP accumulation, and the activation states of protein kinase (ATP: protein phosphotransferase, EC 2.7.1.37), phosphorylase kinase, glycogen synthase, and glycogen phosphorylase have been studied in the isolated perfused rat heart. Perfusion of hearts with isoproterenol (10 or 80 nM) caused enhancement of left ventricular dP/dt (P, pressure), increased intracellular cyclic AMP, increased the activation states of protein kinase, phosphorylase kinase, glycogen phosphorylase, and conversion of glycogen synthase to a less active form. PGE(1) (2 or 30 muM) increased cyclic AMP accumulation and activated protein kinase, but caused no detectable changes in dP/dt or the activation states of the protein kinase substrates involved in glycogen metabolism. Perfusion of hearts with either 10 nM isoproterenol or 30 muM PGE(1) produced comparable increases in cyclic AMP accumulation and protein kinase activity. Exposure of hearts to a combination of these agents caused additive effects on cyclic AMP content and protein kinase activity. However, values for phosphorylase kinase, glycogen phosphorylase, glycogen synthase, and dP/dt did not differ from those observed in the presence of 10 nM isoproterenol alone. The failure of PGE(1) to stimulate phosphorylation of protein kinase substrates was not due to an increase in phosphorylase phosphatase activity. We conclude that an increase in intracellular cyclic AMP and the subsequent activation of protein kinase are insufficient to change either the activities of phosphorylase kinase, glycogen phosphorylase, and glycogen synthase or the inotropic state of heart muscle."}
{"id": "PMID:221899", "title": "Chemical crosslinking of a solubilized enkephalin macromolecular complex.", "content": "Covalently bound [3H]D-Ala2,Met5-enkephalinamide- and 125I-labeled D-Ala2,N-Me-Phe4,Met-(O)5-ol-enkephalin-macromolecule complexes have been prepared by crosslinking the solubilized noncovalent complexes from rat brain. Gel electrophoresis of the partially purified 125I-labeled enkephalin-macromolecule complex under nondenaturing conditions results in a single major/radioactive peak. The complex has a Stokes radius of approximately 48 A as determined by molecular exclusion chromatography; this radius corresponds to a molecular weight of 380,000 for a spherical molecule. In preliminary experiments, sodium dodecyl sulfate electrophoresis of the complex shows a major radioactive peak corresponding to a molecular weight of 35,000. The preparation of these specific covalent enkephalin-macromolecule complexes should be useful in purification of the receptor and in probing the molecular mechanism of opiate action.", "contents": "Chemical crosslinking of a solubilized enkephalin macromolecular complex. Covalently bound [3H]D-Ala2,Met5-enkephalinamide- and 125I-labeled D-Ala2,N-Me-Phe4,Met-(O)5-ol-enkephalin-macromolecule complexes have been prepared by crosslinking the solubilized noncovalent complexes from rat brain. Gel electrophoresis of the partially purified 125I-labeled enkephalin-macromolecule complex under nondenaturing conditions results in a single major/radioactive peak. The complex has a Stokes radius of approximately 48 A as determined by molecular exclusion chromatography; this radius corresponds to a molecular weight of 380,000 for a spherical molecule. In preliminary experiments, sodium dodecyl sulfate electrophoresis of the complex shows a major radioactive peak corresponding to a molecular weight of 35,000. The preparation of these specific covalent enkephalin-macromolecule complexes should be useful in purification of the receptor and in probing the molecular mechanism of opiate action."}
{"id": "PMID:221900", "title": "Avian acute leukemia viruses MC29 and MH2 share specific RNA sequences: evidence for a second class of transforming genes.", "content": "The genome of the defective avian tumor virus MH2 was identified as a RNA of 5.7 kilobases by its presence in different MH2-helper virus complexes and its absence from pure helper virus, by its unique fingerprint pattern of RNase T1-resistant (T1) oligonucleotides that differed from those of two helper virus RNAs, and by its structural analogy to the RNA of MC29, another avian acute leukemia virus. Two sets of sequences were distinguished in MH2 RNA: 66% hybridized with DNA complementary to helper-independent avian tumor viruses, termed group-specific, and 34% were specific. The percentage of specific sequences is considered a minimal estimate because the MH2 RNA used was about 30% contaminated by helper virus RNA. No sequences related to the transforming src gene of avian sarcoma viruses were found in MH2. MH2 shared three large T1 oligonucleotides with MC29, two of which could also be isolated from a RNase A- and T1-resistant hybrid formed between MH2 RNA and MC29 specific cDNA. These oligonucleotides belong to a group of six that define the specific segment of MC29 RNA described previously. The group-specific sequences of MH2 and MC29 RNA shared only the two smallest out of about 20 T1 oligonucleotides associated with MH2 RNA. It is concluded that the specific sequences of MH2 and MC29 are related, and it is proposed that they are necessary for, or identical with, the onc genes of these viruses. These sequences would define a related class of transforming genes in avian tumor viruses that differs from the src genes of avian sarcoma viruses.", "contents": "Avian acute leukemia viruses MC29 and MH2 share specific RNA sequences: evidence for a second class of transforming genes. The genome of the defective avian tumor virus MH2 was identified as a RNA of 5.7 kilobases by its presence in different MH2-helper virus complexes and its absence from pure helper virus, by its unique fingerprint pattern of RNase T1-resistant (T1) oligonucleotides that differed from those of two helper virus RNAs, and by its structural analogy to the RNA of MC29, another avian acute leukemia virus. Two sets of sequences were distinguished in MH2 RNA: 66% hybridized with DNA complementary to helper-independent avian tumor viruses, termed group-specific, and 34% were specific. The percentage of specific sequences is considered a minimal estimate because the MH2 RNA used was about 30% contaminated by helper virus RNA. No sequences related to the transforming src gene of avian sarcoma viruses were found in MH2. MH2 shared three large T1 oligonucleotides with MC29, two of which could also be isolated from a RNase A- and T1-resistant hybrid formed between MH2 RNA and MC29 specific cDNA. These oligonucleotides belong to a group of six that define the specific segment of MC29 RNA described previously. The group-specific sequences of MH2 and MC29 RNA shared only the two smallest out of about 20 T1 oligonucleotides associated with MH2 RNA. It is concluded that the specific sequences of MH2 and MC29 are related, and it is proposed that they are necessary for, or identical with, the onc genes of these viruses. These sequences would define a related class of transforming genes in avian tumor viruses that differs from the src genes of avian sarcoma viruses."}
{"id": "PMID:221901", "title": "Enzyme-catalyzed DNA unwinding: studies on Escherichia coli rep protein.", "content": "Replication in vitro of the replicative form (RF) I DNA of bacteriophage varphiX174 requires the phage-induced cistron A (cisA) protein, the host rep protein, DNA-binding protein, ATP, and DNA polymerase III plus replication factors. The rep protein is a single-stranded DNA-dependent ATPase. In this paper we show that varphiX174 RF I DNA cut by the cisA protein acts as a duplex DNA cofactor for the rep protein ATPase activity, provided that DNA-binding protein is present. In this latter reaction the duplex DNA is unwound by the rep protein with concomitant hydrolysis of ATP. The extents of ATP hydrolysis, DNA unwinding, and, where appropriate, DNA synthesis are proportional to the amounts of DNA-binding protein present. Two ATP molecules are hydrolyzed per base pair unwound. We propose that the obligatory requirement for the cisA protein in the unwinding of varphiX174 RF I DNA is not simply due to its endonuclease activity but rather is due to its provision of a site for the binding of the rep protein. The rep protein in the presence of DNA-binding protein, but in the absence of cisA protein, unwinds duplex DNA when one strand extends to generate a single-stranded leader region preceding the duplex. We show that rep protein translocates along the leader single strand in a 5'-to-3' direction only and then invades the duplex DNA. The rep protein shows a directional specificity for translocation and unwinding. A model is presented to explain the mechanism of DNA unwinding catalyzed by the rep protein.", "contents": "Enzyme-catalyzed DNA unwinding: studies on Escherichia coli rep protein. Replication in vitro of the replicative form (RF) I DNA of bacteriophage varphiX174 requires the phage-induced cistron A (cisA) protein, the host rep protein, DNA-binding protein, ATP, and DNA polymerase III plus replication factors. The rep protein is a single-stranded DNA-dependent ATPase. In this paper we show that varphiX174 RF I DNA cut by the cisA protein acts as a duplex DNA cofactor for the rep protein ATPase activity, provided that DNA-binding protein is present. In this latter reaction the duplex DNA is unwound by the rep protein with concomitant hydrolysis of ATP. The extents of ATP hydrolysis, DNA unwinding, and, where appropriate, DNA synthesis are proportional to the amounts of DNA-binding protein present. Two ATP molecules are hydrolyzed per base pair unwound. We propose that the obligatory requirement for the cisA protein in the unwinding of varphiX174 RF I DNA is not simply due to its endonuclease activity but rather is due to its provision of a site for the binding of the rep protein. The rep protein in the presence of DNA-binding protein, but in the absence of cisA protein, unwinds duplex DNA when one strand extends to generate a single-stranded leader region preceding the duplex. We show that rep protein translocates along the leader single strand in a 5'-to-3' direction only and then invades the duplex DNA. The rep protein shows a directional specificity for translocation and unwinding. A model is presented to explain the mechanism of DNA unwinding catalyzed by the rep protein."}
{"id": "PMID:221902", "title": "Restriction enzyme analysis of mouse cellular type C viral DNA: emergence of new viral sequences in spontaneous AKR/J lymphomas.", "content": "The topography of endogenous type C viral sequences in mouse cellular DNA was investigated by EcoRI nuclease restriction and application of the Southern blotting technique. The DNAs from one outbred and five inbred strains were resolved into 20-35 fragments containing viral sequences, distributed in unique, though related, patterns for each mouse strain. Different normal tissues from the same animal were indistinguishable in their DNA patterns, suggesting that tissue differentiation is not associated with gross alteration in the topography of endogenous type C virus sequences. Tumor tissues from spontaneous lymphomas of AKR/J mice were similarly analyzed. In four out of seven individual tumors we detected the emergence of one or two new virus-containing DNA fragments. The mass of these fragment varied, indicating different insertion sites of the new viral sequences. The detection of these new viral sequences suggests that each tumor was composed of descendents of only one or a few cells.", "contents": "Restriction enzyme analysis of mouse cellular type C viral DNA: emergence of new viral sequences in spontaneous AKR/J lymphomas. The topography of endogenous type C viral sequences in mouse cellular DNA was investigated by EcoRI nuclease restriction and application of the Southern blotting technique. The DNAs from one outbred and five inbred strains were resolved into 20-35 fragments containing viral sequences, distributed in unique, though related, patterns for each mouse strain. Different normal tissues from the same animal were indistinguishable in their DNA patterns, suggesting that tissue differentiation is not associated with gross alteration in the topography of endogenous type C virus sequences. Tumor tissues from spontaneous lymphomas of AKR/J mice were similarly analyzed. In four out of seven individual tumors we detected the emergence of one or two new virus-containing DNA fragments. The mass of these fragment varied, indicating different insertion sites of the new viral sequences. The detection of these new viral sequences suggests that each tumor was composed of descendents of only one or a few cells."}
{"id": "PMID:221903", "title": "An Escherichia coli mutant defective in single-strand binding protein is defective in DNA replication.", "content": "An Escherichia coli mutant, temperature-sensitive for DNA synthesis in vivo and in vitro, is defective in single-strand binding protein (SSB; DNA-binding protein). Conversion of phage G4 single strands to the duplex form is defective in crude enzyme fractions of the mutant and is complemented by pure wild-type SSB. Radioimmunoassays of mutant extracts show normal levels of material crossreacting with anti-SSB antibody. SSB purified to homogeneity from the mutant is active, with lower specific activity, in the reconstituted G4 replication assay at 30 degrees C, but virtually inactive at 42 degrees C. Surprisingly, the mutant protein, like the wild-type protein, survives heating at 100 degrees C. Thus, mutant SSB is structurally heat-resistant but is functionally thermosensitive in vitro and in vivo. Both the in vivo and in vitro defects are tightly linked in transductions by phage P1. The mutation in the binding protein, designated ssb-1, is located between 90 and 91 min on the E. coli genetic map.", "contents": "An Escherichia coli mutant defective in single-strand binding protein is defective in DNA replication. An Escherichia coli mutant, temperature-sensitive for DNA synthesis in vivo and in vitro, is defective in single-strand binding protein (SSB; DNA-binding protein). Conversion of phage G4 single strands to the duplex form is defective in crude enzyme fractions of the mutant and is complemented by pure wild-type SSB. Radioimmunoassays of mutant extracts show normal levels of material crossreacting with anti-SSB antibody. SSB purified to homogeneity from the mutant is active, with lower specific activity, in the reconstituted G4 replication assay at 30 degrees C, but virtually inactive at 42 degrees C. Surprisingly, the mutant protein, like the wild-type protein, survives heating at 100 degrees C. Thus, mutant SSB is structurally heat-resistant but is functionally thermosensitive in vitro and in vivo. Both the in vivo and in vitro defects are tightly linked in transductions by phage P1. The mutation in the binding protein, designated ssb-1, is located between 90 and 91 min on the E. coli genetic map."}
{"id": "PMID:221904", "title": "Identification of the messenger RNAs coding for the gag and env gene products of the murine mammary tumor virus.", "content": "Full-length (35S) genomic RNA from murine mammary tumor virus (MuMTV) was translated in vitro, using a reticulocyte lysate system, into proteins of 105,000, 75,000, 65,000, 35,000, and 27,000 daltons. These proteins were all immunoprecipitable with a monospecific antiserum to the major viral core protein, p27, but not with antiserum to the major viral envelope glycoprotein, gp47. Translation in vitro of RNA of about 24S size extracted from MuMTV yielded proteins similar in size and immunoreactivity to the products of the 35S RNA translation. Polyadenylylated RNA isolated from an MuMTV-producing cell line was fractionated according to size by velocity sedimentation and subsequently hybridized to MuMTV complementary DNA probes. These studies identified at least three size classes (35S, 24S, and 14-18S) of intracellular MuMTV-specific RNA. The 35S intracellular RNA was translated into MuMTV-specific proteins identical in size and immunoreactivity to the products of the virion-derived 35S RNA. On the other hand, translation of the intracellular 24S RNA fraction resulted in the synthesis of proteins, of which two (of about 70,000 daltons) could be immunoprecipitated with anti-gp47 serum, but not with anti-p27 serum. From these data we conclude that MuMTV core and envelope proteins are synthesized from two different mRNAs with approximate sizes of 35S and 24S, respectively. Our results also imply that the intracellular 24S mRNA is synthesized by a process more complex than simple cleavage of the 35S RNA.", "contents": "Identification of the messenger RNAs coding for the gag and env gene products of the murine mammary tumor virus. Full-length (35S) genomic RNA from murine mammary tumor virus (MuMTV) was translated in vitro, using a reticulocyte lysate system, into proteins of 105,000, 75,000, 65,000, 35,000, and 27,000 daltons. These proteins were all immunoprecipitable with a monospecific antiserum to the major viral core protein, p27, but not with antiserum to the major viral envelope glycoprotein, gp47. Translation in vitro of RNA of about 24S size extracted from MuMTV yielded proteins similar in size and immunoreactivity to the products of the 35S RNA translation. Polyadenylylated RNA isolated from an MuMTV-producing cell line was fractionated according to size by velocity sedimentation and subsequently hybridized to MuMTV complementary DNA probes. These studies identified at least three size classes (35S, 24S, and 14-18S) of intracellular MuMTV-specific RNA. The 35S intracellular RNA was translated into MuMTV-specific proteins identical in size and immunoreactivity to the products of the virion-derived 35S RNA. On the other hand, translation of the intracellular 24S RNA fraction resulted in the synthesis of proteins, of which two (of about 70,000 daltons) could be immunoprecipitated with anti-gp47 serum, but not with anti-p27 serum. From these data we conclude that MuMTV core and envelope proteins are synthesized from two different mRNAs with approximate sizes of 35S and 24S, respectively. Our results also imply that the intracellular 24S mRNA is synthesized by a process more complex than simple cleavage of the 35S RNA."}
{"id": "PMID:221905", "title": "Accelerated clearance of low-density and high-density lipoproteins and retarded clearance of E apoprotein-containing lipoproteins from the plasma of rats after modification of lysine residues.", "content": "Selective chemical modification of lysine residues of lipoproteins by acetoacetylation dramatically altered the metabolism of the lipoproteins without significantly altering other physical or chemical properties. Modification of 30-60% of the total lysine residues of iodinated rat or human low-density lipoproteins ((125)I-LDL) resulted in a rapid removal of these acetoacetylated lipoproteins from the plasma of rats. Within minutes after intravenous injection into intact rats, greater than 80% of the total injected dose disappeared from the plasma. The rapidly cleared acetoacetylated LDL appeared in the liver, and within 6-30 min as much as 50-80% of the total injected dose of modified LDL could be accounted for in the liver. Furthermore, it was possible to demonstrate in the isolated perfused rat liver that the Kupffer cells were responsible for the lipoprotein uptake. Human high-density lipoproteins (HDL(3)) were also rapidly removed from the plasma after acetoacetylation. In striking contrast, acetoacetylation (30-60%) of two E apoprotein-containing lipoproteins (rat HDL(1) and dog HDL(c)) retarded their removal from the plasma. The accelerated removal of modified LDL and HDL(3), in contrast to the retarded removal of modified HDL(1) and HDL(c), suggests that the recognition and removal process is specific for a property acquired by only certain lipoproteins after acetoacetylation. Moreover, these results suggest that lysine residues of the E apoprotein may play a functional role in the recognition process for the normal clearance of HDL(1) and HDL(c), a process that is interfered with after acetoacetylation.", "contents": "Accelerated clearance of low-density and high-density lipoproteins and retarded clearance of E apoprotein-containing lipoproteins from the plasma of rats after modification of lysine residues. Selective chemical modification of lysine residues of lipoproteins by acetoacetylation dramatically altered the metabolism of the lipoproteins without significantly altering other physical or chemical properties. Modification of 30-60% of the total lysine residues of iodinated rat or human low-density lipoproteins ((125)I-LDL) resulted in a rapid removal of these acetoacetylated lipoproteins from the plasma of rats. Within minutes after intravenous injection into intact rats, greater than 80% of the total injected dose disappeared from the plasma. The rapidly cleared acetoacetylated LDL appeared in the liver, and within 6-30 min as much as 50-80% of the total injected dose of modified LDL could be accounted for in the liver. Furthermore, it was possible to demonstrate in the isolated perfused rat liver that the Kupffer cells were responsible for the lipoprotein uptake. Human high-density lipoproteins (HDL(3)) were also rapidly removed from the plasma after acetoacetylation. In striking contrast, acetoacetylation (30-60%) of two E apoprotein-containing lipoproteins (rat HDL(1) and dog HDL(c)) retarded their removal from the plasma. The accelerated removal of modified LDL and HDL(3), in contrast to the retarded removal of modified HDL(1) and HDL(c), suggests that the recognition and removal process is specific for a property acquired by only certain lipoproteins after acetoacetylation. Moreover, these results suggest that lysine residues of the E apoprotein may play a functional role in the recognition process for the normal clearance of HDL(1) and HDL(c), a process that is interfered with after acetoacetylation."}
{"id": "PMID:221906", "title": "Purification to homogeneity of camel pituitary pro-opiocortin, the common precursor of opioid peptides and corticotropin.", "content": "Pro-opiocortin was purified from camel pituitaries by procedures including high-performance liquid chromatography. The precursor relationship of the pure protein to the opioid peptides and to corticotropin was confirmed. Partial chemical analysis consisting of amino acid analysis and tryptic peptide mapping was carried out with the aid of sensitive fluorescence detection.", "contents": "Purification to homogeneity of camel pituitary pro-opiocortin, the common precursor of opioid peptides and corticotropin. Pro-opiocortin was purified from camel pituitaries by procedures including high-performance liquid chromatography. The precursor relationship of the pure protein to the opioid peptides and to corticotropin was confirmed. Partial chemical analysis consisting of amino acid analysis and tryptic peptide mapping was carried out with the aid of sensitive fluorescence detection."}
{"id": "PMID:221907", "title": "Uninfected vertebrate cells contain a protein that is closely related to the product of the avian sarcoma virus transforming gene (src).", "content": "Neoplastic transformation of cell by avian sarcoma virus is mediated by a single viral gene (src), which encodes a phosphoprotein (pp60src) with the enzymatic activity of a protein kinase. The DNAs of vertebrate species contain a highly conserved homologue of src that is also represented in the polysomal RNA of uninfected cells and, hence, may specify a normal cellular protein. We have used antisera directed against pp60src to isolate a closely related phosphoprotein (denoted vertebrate pp60) from uninfected chicken, quail, rat, and human cells. Our data indicate that vertebrate pp60 is a homologue of pp60src, highly conserved both antigenically and chemically. Moreover, the cellular protein may possess protein kinase activity similar to that associated with pp60src. We conclude that the product of src is a slightly modified analogue of a normal cellular protein.", "contents": "Uninfected vertebrate cells contain a protein that is closely related to the product of the avian sarcoma virus transforming gene (src). Neoplastic transformation of cell by avian sarcoma virus is mediated by a single viral gene (src), which encodes a phosphoprotein (pp60src) with the enzymatic activity of a protein kinase. The DNAs of vertebrate species contain a highly conserved homologue of src that is also represented in the polysomal RNA of uninfected cells and, hence, may specify a normal cellular protein. We have used antisera directed against pp60src to isolate a closely related phosphoprotein (denoted vertebrate pp60) from uninfected chicken, quail, rat, and human cells. Our data indicate that vertebrate pp60 is a homologue of pp60src, highly conserved both antigenically and chemically. Moreover, the cellular protein may possess protein kinase activity similar to that associated with pp60src. We conclude that the product of src is a slightly modified analogue of a normal cellular protein."}
{"id": "PMID:221908", "title": "Solubilized and insolubilized bone morphogenetic protein.", "content": "A bone morphogenetic protein (BMP) obtained in solution by digestion of demineralized rabbit cortical bone matrix with bacterial collagenase retains its biologically active conformation in a neutral salt/ethylene glycol mixture. BMP may be insolubilized by coprecipitation with calcium phosphate and resolubilized by chemical extraction with a neutral salt in the same solvent mixture. Upon concanavalin A-Sepharose chromatography, BMP is bound by hydrophobic interaction and carbohydrate recognition and is recovered by elution with either alpha-methyl mannoside or ethylene glycol solvent mixture. Implants of both eluates and the extracts of the coprecipitate in double-walled diffusion chambers induce transmembrane bone morphogenesis. BMP is not species specific; rabbit BMP induces new bone formation in the rat. The present observations indicate that BMP is a glycoprotein.", "contents": "Solubilized and insolubilized bone morphogenetic protein. A bone morphogenetic protein (BMP) obtained in solution by digestion of demineralized rabbit cortical bone matrix with bacterial collagenase retains its biologically active conformation in a neutral salt/ethylene glycol mixture. BMP may be insolubilized by coprecipitation with calcium phosphate and resolubilized by chemical extraction with a neutral salt in the same solvent mixture. Upon concanavalin A-Sepharose chromatography, BMP is bound by hydrophobic interaction and carbohydrate recognition and is recovered by elution with either alpha-methyl mannoside or ethylene glycol solvent mixture. Implants of both eluates and the extracts of the coprecipitate in double-walled diffusion chambers induce transmembrane bone morphogenesis. BMP is not species specific; rabbit BMP induces new bone formation in the rat. The present observations indicate that BMP is a glycoprotein."}
{"id": "PMID:221909", "title": "Vaccinia virus replication requires active participation of the host cell transcriptional apparatus.", "content": "The ability of vaccinia virus to replicate in BSC-40 monkey cells whose nuclei have been functionally inactivated was examined. Exposure of cell monolayers to ultraviolet radiation at doses that did not alter the cells' capacity to support a subsequent infection by a cytoplasmic virus (vesicular stomatitis virus) caused a reduction to less than 10% in the observed yield of infectious progeny from vaccinia virus and herpes simplex virus (type 1) infections. Similarly, replication  of vaccinia virus was reduced to 5% by treatment of BCS-40 cells with alpha-amanitin (10 microgram/ml), a potent inhibitor of nuclear mRNA synthesis. In both situations, ultraviolet irradiation and alpha-amanitin treatment, early and late vaccinia viral genes were expressed at high levels, but the newly synthesized virion components were not assembled into mature infectious particles. Taken together, these data suggest that the active involvement of the host cell nuclear transcriptive system is obligatory in the vaccinia virus replicative cycle.", "contents": "Vaccinia virus replication requires active participation of the host cell transcriptional apparatus. The ability of vaccinia virus to replicate in BSC-40 monkey cells whose nuclei have been functionally inactivated was examined. Exposure of cell monolayers to ultraviolet radiation at doses that did not alter the cells' capacity to support a subsequent infection by a cytoplasmic virus (vesicular stomatitis virus) caused a reduction to less than 10% in the observed yield of infectious progeny from vaccinia virus and herpes simplex virus (type 1) infections. Similarly, replication  of vaccinia virus was reduced to 5% by treatment of BCS-40 cells with alpha-amanitin (10 microgram/ml), a potent inhibitor of nuclear mRNA synthesis. In both situations, ultraviolet irradiation and alpha-amanitin treatment, early and late vaccinia viral genes were expressed at high levels, but the newly synthesized virion components were not assembled into mature infectious particles. Taken together, these data suggest that the active involvement of the host cell nuclear transcriptive system is obligatory in the vaccinia virus replicative cycle."}
{"id": "PMID:221910", "title": "Mutations in cyclic AMP-dependent protein kinase and corticotropin (ACTH)-sensitive adenylate cyclase affect adrenal steroidogenesis.", "content": "Two groups of mutant clones were isolated from YI adrenocortical tumor cells. One group, Y1(Kin), exhibited altered cytosolic cyclic AMP-dependent protein kinase activity; the second group, Y1(Cyc), exhibited diminished corticotropin-responsive adenylate cyclase activity. Steroidogenic responses to corticotropin and cyclic nucleotides closely paralleled cyclic AMP-dependent protein kinase activity in the Y1(Kin) mutants. In Y1(Cyc) mutants, corticotropin had little effect on steroidogenesis, whereas cyclic nucleotides were fully active. These data imply that adenylate cyclase and cyclic AMP-dependent protein kinase are obligatory components of the corticotropin-stimulated steroidogenic pathway.", "contents": "Mutations in cyclic AMP-dependent protein kinase and corticotropin (ACTH)-sensitive adenylate cyclase affect adrenal steroidogenesis. Two groups of mutant clones were isolated from YI adrenocortical tumor cells. One group, Y1(Kin), exhibited altered cytosolic cyclic AMP-dependent protein kinase activity; the second group, Y1(Cyc), exhibited diminished corticotropin-responsive adenylate cyclase activity. Steroidogenic responses to corticotropin and cyclic nucleotides closely paralleled cyclic AMP-dependent protein kinase activity in the Y1(Kin) mutants. In Y1(Cyc) mutants, corticotropin had little effect on steroidogenesis, whereas cyclic nucleotides were fully active. These data imply that adenylate cyclase and cyclic AMP-dependent protein kinase are obligatory components of the corticotropin-stimulated steroidogenic pathway."}
{"id": "PMID:221911", "title": "Thyrotropin is not a growth factor for human thyroid cells in culture.", "content": "Thyroid cells, obtained from both normal human tissue and benign nodular goiter, were cultured and maintained in vitro in 4-18 passages. Cultures with confluent cells accumulated cyclic AMP (10-150 times the basal amount) upon addition of bovine thyrotropin (100 milliunits/ml), indicating that the cells in culture maintained a thyrotropin-sensitive adenylate cyclase system. Addition of high doses of thyrotropin also induced a characteristic and reversible change in the morphology of the cells. The effect of thyrotropin on cell growth was studied in short- and long-term experiments. Thyrotropin reduced [(3)H]thymidine incorporation in a dose-dependent fashion in all cultures of thyroid cells. The maximal inhibition over a 24-hr period was about 50%. The thyroid cells were notably sensitive, and the half-maximal effect occurred at about 100 milliunits of thyrotropin per ml. In contrast, the hormone had no effect on [(3)H]-thymidine incorporation into human glial cells. Low doses of thyrotropin also had no effect on human fibroblasts and, at high doses, a stimulation of [(3)H]thymidine incorporation was seen. Thyroid cell cultures grown in the presence of 10 milliunits of thyrotropin per ml for 7-14 days had a slower growth rate and 24-36% lower cell numbers at saturation density than control dishes, indicating that the hormone also had a long-term effect on cell proliferation. The data agree with in vitro studies by others of the effects of corticotropin and lutropin on target cells and suggest that in vivo the primary action of pituitary trophic hormones on endocrine tissues is not stimulation of growth.", "contents": "Thyrotropin is not a growth factor for human thyroid cells in culture. Thyroid cells, obtained from both normal human tissue and benign nodular goiter, were cultured and maintained in vitro in 4-18 passages. Cultures with confluent cells accumulated cyclic AMP (10-150 times the basal amount) upon addition of bovine thyrotropin (100 milliunits/ml), indicating that the cells in culture maintained a thyrotropin-sensitive adenylate cyclase system. Addition of high doses of thyrotropin also induced a characteristic and reversible change in the morphology of the cells. The effect of thyrotropin on cell growth was studied in short- and long-term experiments. Thyrotropin reduced [(3)H]thymidine incorporation in a dose-dependent fashion in all cultures of thyroid cells. The maximal inhibition over a 24-hr period was about 50%. The thyroid cells were notably sensitive, and the half-maximal effect occurred at about 100 milliunits of thyrotropin per ml. In contrast, the hormone had no effect on [(3)H]-thymidine incorporation into human glial cells. Low doses of thyrotropin also had no effect on human fibroblasts and, at high doses, a stimulation of [(3)H]thymidine incorporation was seen. Thyroid cell cultures grown in the presence of 10 milliunits of thyrotropin per ml for 7-14 days had a slower growth rate and 24-36% lower cell numbers at saturation density than control dishes, indicating that the hormone also had a long-term effect on cell proliferation. The data agree with in vitro studies by others of the effects of corticotropin and lutropin on target cells and suggest that in vivo the primary action of pituitary trophic hormones on endocrine tissues is not stimulation of growth."}
{"id": "PMID:221912", "title": "Human placental immunoreactive corticotropin, lipotropin, and beta-endorphin: evidence for a common precursor.", "content": "The concentrations and molecular sizes of immunoreactive corticotropin (ACTH), lipotropin (LPH, beta LPH plus gamma LPH), gamma LPH, and beta-endorphin (beta END) were determined in human placental extracts. Serial dilutions of a water extract of placenta generated competitive binding curves parallel with that of the standard in each assay. The concentrations of ACTH, LPH, gamma LPH, and beta END were 3.3, 0.8, 0.7, and 1.1 ng/g wet weight of tissue, respectively. A partially purified extract applied to a Sephadex G-50 column contained high Mr components with ACTH, LPH, gamma LPH, and beta END immunoreactivities. The extract was applied to an immune affinity chromatography column consisting of affinity-purified (1-24)ACTH antiserum covalently bound to agarose. The material that adsorbed to the column and eluted with buffer containing sodium dodecyl sulfate had ACTH, LPH, and beta END immunoreactivities, indicating that there was a component or components containing antigenic determinants for all of these peptides. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis of the affinity-purified placental extract revealed at least two high Mr components (Mr approximately 48,000 and 36,000) with all three immunoreactivities. These data suggest, but do not prove, that the placenta synthesizes ACTH, the LPHs, and beta END from a common precursor molecule.", "contents": "Human placental immunoreactive corticotropin, lipotropin, and beta-endorphin: evidence for a common precursor. The concentrations and molecular sizes of immunoreactive corticotropin (ACTH), lipotropin (LPH, beta LPH plus gamma LPH), gamma LPH, and beta-endorphin (beta END) were determined in human placental extracts. Serial dilutions of a water extract of placenta generated competitive binding curves parallel with that of the standard in each assay. The concentrations of ACTH, LPH, gamma LPH, and beta END were 3.3, 0.8, 0.7, and 1.1 ng/g wet weight of tissue, respectively. A partially purified extract applied to a Sephadex G-50 column contained high Mr components with ACTH, LPH, gamma LPH, and beta END immunoreactivities. The extract was applied to an immune affinity chromatography column consisting of affinity-purified (1-24)ACTH antiserum covalently bound to agarose. The material that adsorbed to the column and eluted with buffer containing sodium dodecyl sulfate had ACTH, LPH, and beta END immunoreactivities, indicating that there was a component or components containing antigenic determinants for all of these peptides. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis of the affinity-purified placental extract revealed at least two high Mr components (Mr approximately 48,000 and 36,000) with all three immunoreactivities. These data suggest, but do not prove, that the placenta synthesizes ACTH, the LPHs, and beta END from a common precursor molecule."}
{"id": "PMID:221913", "title": "Detection of a nuclear antigen in Herpesvirus ateles-carrying marmoset lines by the acid-fixed nuclear binding technique.", "content": "In vitro binding of a Herpesvirus ateles (HVA)-associated soluble antigen to amphibian erythrocyte nuclei was demonstrated by the acid-fixed nuclear binding technique in combination with anticomplement immunofluorescence. Incubation of concentrated salt-extracted soluble antigens derived from HVA-carrying marmoset lines with methanol/acetic acid-fixed erythrocytes of frogs and salamanders resulted in a brilliant nuclear fluorescence after exposure to a live virus-boostered, anti-HVS-positive squirrel monkey serum. Anti-HVS-negative sera did not stain. The activity of the positive serum could be abosrbed completely with extracts of HVA-carrying cells but not with Epstein-Barr virus-carrying or Herpesvirus papio-carrying cells. The HVA-associated antigen was also present in lytically HVA-infected marmoset kidney cells.", "contents": "Detection of a nuclear antigen in Herpesvirus ateles-carrying marmoset lines by the acid-fixed nuclear binding technique. In vitro binding of a Herpesvirus ateles (HVA)-associated soluble antigen to amphibian erythrocyte nuclei was demonstrated by the acid-fixed nuclear binding technique in combination with anticomplement immunofluorescence. Incubation of concentrated salt-extracted soluble antigens derived from HVA-carrying marmoset lines with methanol/acetic acid-fixed erythrocytes of frogs and salamanders resulted in a brilliant nuclear fluorescence after exposure to a live virus-boostered, anti-HVS-positive squirrel monkey serum. Anti-HVS-negative sera did not stain. The activity of the positive serum could be abosrbed completely with extracts of HVA-carrying cells but not with Epstein-Barr virus-carrying or Herpesvirus papio-carrying cells. The HVA-associated antigen was also present in lytically HVA-infected marmoset kidney cells."}
{"id": "PMID:221914", "title": "beta-Adrenergic receptor regulation by agonists and membrane depolarization in rat brain slices.", "content": "Rat cerebral cortex slices exposed to (-)-isoproterenol and then washed accumulated significantly less cyclic AMP when rechallenged with isoproterenol than did control slices. The isoproterenol-induced desensitization was associated with a concurrent reduction in [3H]dihydroalprenolol membrane binding but with no change in the affinity of [3H]dihydroalprenolol or isoproterenol for the binding sites. beta-Adrenergic receptor desensitization was rapidly reversed by slice depolarization with high-[K+] buffers, batrachotoxin, grayanotoxin, or veratridine, even in the continued presence of isoproterenol. Restoration of binding by grayanotoxin was prevented by tetrodotoxin or by removing Na+ from the buffer. These data demonstrate partial participation of the membrane receptor in beta-adrenergic desensitization of rat brain slices and suggest that brain beta-adrenergic receptors, like cholinergic receptors in skeletal muscle and alpha-adrenergic receptors in rat parotid, are regulated in part by membrane voltage.", "contents": "beta-Adrenergic receptor regulation by agonists and membrane depolarization in rat brain slices. Rat cerebral cortex slices exposed to (-)-isoproterenol and then washed accumulated significantly less cyclic AMP when rechallenged with isoproterenol than did control slices. The isoproterenol-induced desensitization was associated with a concurrent reduction in [3H]dihydroalprenolol membrane binding but with no change in the affinity of [3H]dihydroalprenolol or isoproterenol for the binding sites. beta-Adrenergic receptor desensitization was rapidly reversed by slice depolarization with high-[K+] buffers, batrachotoxin, grayanotoxin, or veratridine, even in the continued presence of isoproterenol. Restoration of binding by grayanotoxin was prevented by tetrodotoxin or by removing Na+ from the buffer. These data demonstrate partial participation of the membrane receptor in beta-adrenergic desensitization of rat brain slices and suggest that brain beta-adrenergic receptors, like cholinergic receptors in skeletal muscle and alpha-adrenergic receptors in rat parotid, are regulated in part by membrane voltage."}
{"id": "PMID:221915", "title": "Codon-anticodon interaction at the ribosomal P (peptidyl-tRNA)site.", "content": "A method for binding tRNA to ribosomes, introduced by Watanabe [Watanabe, S. (1972) J. Mol. Biol. 67, 443-457], permits nonenzymatic binding of N-acetyl-Phe-tRNA(Phe) to either the ribosomal aminoacyl-tRNA (A) or peptidyl-tRNA (P) site with almost 100% specificity. We used this method to analyze a possible codon-anticodon interaction at the P site for NH(2)-blocked aminoacyl-tRNA and deacylated tRNA. N-Acetyl-Phe-tRNA(Phe) bound only to the P site of poly(U)-programmed 70S ribosomes, not to poly(A)-programmed ribosomes. The reverse mRNA dependence was found for N-acetyl-Lys-tRNA(Lys). A series of purified deacylated tRNAs was analyzed in the poly(U) and poly(A) system for abilities to block P-site binding of N-acetyl-aminoacyl-tRNA and to direct the N-acetyl-aminoacyl-tRNA to the A site. Only the cognate tRNA was as effective as the bulk tRNA at a concentration of less than 1/20th that of bulk tRNA. tRNAs whose corresponding codons are identical or similar (same base character) in the first two codon positions showed a low but significant effect. The other noncognate tRNAs were unable to direct the NH(2)-blocked aminoacyl-tRNAs to the A site. Chlortetracycline interfered neither with the P-site binding of NH(2)-blocked aminoacyl-tRNA nor with the effects of deacylated tRNAs. Furthermore, the translocation blocker viomycin affected neither the binding to the A site nor that to the P site. These effects of both antibiotics indicate that both kinds of tRNA do not bind transiently in the A site before filling the P site and that codon-anticodon interaction takes place at the P site.", "contents": "Codon-anticodon interaction at the ribosomal P (peptidyl-tRNA)site. A method for binding tRNA to ribosomes, introduced by Watanabe [Watanabe, S. (1972) J. Mol. Biol. 67, 443-457], permits nonenzymatic binding of N-acetyl-Phe-tRNA(Phe) to either the ribosomal aminoacyl-tRNA (A) or peptidyl-tRNA (P) site with almost 100% specificity. We used this method to analyze a possible codon-anticodon interaction at the P site for NH(2)-blocked aminoacyl-tRNA and deacylated tRNA. N-Acetyl-Phe-tRNA(Phe) bound only to the P site of poly(U)-programmed 70S ribosomes, not to poly(A)-programmed ribosomes. The reverse mRNA dependence was found for N-acetyl-Lys-tRNA(Lys). A series of purified deacylated tRNAs was analyzed in the poly(U) and poly(A) system for abilities to block P-site binding of N-acetyl-aminoacyl-tRNA and to direct the N-acetyl-aminoacyl-tRNA to the A site. Only the cognate tRNA was as effective as the bulk tRNA at a concentration of less than 1/20th that of bulk tRNA. tRNAs whose corresponding codons are identical or similar (same base character) in the first two codon positions showed a low but significant effect. The other noncognate tRNAs were unable to direct the NH(2)-blocked aminoacyl-tRNAs to the A site. Chlortetracycline interfered neither with the P-site binding of NH(2)-blocked aminoacyl-tRNA nor with the effects of deacylated tRNAs. Furthermore, the translocation blocker viomycin affected neither the binding to the A site nor that to the P site. These effects of both antibiotics indicate that both kinds of tRNA do not bind transiently in the A site before filling the P site and that codon-anticodon interaction takes place at the P site."}
{"id": "PMID:221916", "title": "Corticotropin and beta-endorphin: construction and analysis of recombinant DNA complementary to mRNA for the common precursor.", "content": "A cDNA fragment synthesized from mouse mRNA (ACTH/LPH mRNA) that codes for the precursor polypeptide containing corticotropin (ACTH), beta-lipotropin (LPH), and several other peptides has been cloned in bacteria. The mRNA was enriched for ACTH/LPH mRNA translational activity (to about 75%) prior to cDNA synthesis. It appears to contain about 1200 bases, of which approximately 450 bases are not translated. The cloned DNA fragment is complementary to the region of the mRNA coding for the protein fragment beta-LPH-(44--90); this contains all of the amino acids of [Met]-enkephalin (residues 61--65 of beta-LPH), most of the amino acids of beta-melanocyte-stimulating hormone, and all but the carboxy-terminal amino acid of beta-endorphin. Based on assignment of the amino acid sequence of mouse beta-LPH from the nucelic acid sequence, it appears that there is extensive homology of mouse beta-LPH with human and porcine beta-LPH. The data also establish the linkage between beta-melanocyte-stimulating hormone and beta-endorphin as a Lys-Arg sequence. It is hoped that this cloned DNA can be used as a probe to study the expression and structure of the ACTH/LPH gene.", "contents": "Corticotropin and beta-endorphin: construction and analysis of recombinant DNA complementary to mRNA for the common precursor. A cDNA fragment synthesized from mouse mRNA (ACTH/LPH mRNA) that codes for the precursor polypeptide containing corticotropin (ACTH), beta-lipotropin (LPH), and several other peptides has been cloned in bacteria. The mRNA was enriched for ACTH/LPH mRNA translational activity (to about 75%) prior to cDNA synthesis. It appears to contain about 1200 bases, of which approximately 450 bases are not translated. The cloned DNA fragment is complementary to the region of the mRNA coding for the protein fragment beta-LPH-(44--90); this contains all of the amino acids of [Met]-enkephalin (residues 61--65 of beta-LPH), most of the amino acids of beta-melanocyte-stimulating hormone, and all but the carboxy-terminal amino acid of beta-endorphin. Based on assignment of the amino acid sequence of mouse beta-LPH from the nucelic acid sequence, it appears that there is extensive homology of mouse beta-LPH with human and porcine beta-LPH. The data also establish the linkage between beta-melanocyte-stimulating hormone and beta-endorphin as a Lys-Arg sequence. It is hoped that this cloned DNA can be used as a probe to study the expression and structure of the ACTH/LPH gene."}
{"id": "PMID:221917", "title": "Structural studies on oncornavirus-related sequences in chicken genomic DNA: two-step analyses of EcoRI and Bgl I restriction digests and tentative mapping of a ubiquitous endogenous provirus digests and tentative mapping of a ubiquitous endogenous provirus.", "content": "DNA from a variety of uninfected chicken cell types has been analyzed by using restriction endonuclease digestion and RPC-5 ion-exchange chromatography followed by agarose gel electrophoresis. Endogenous retrovirus sequences were detected by using a 32P-labeled avian leukosis viral RNA probe. One simple pattern was identified in an individual containing unexpressed endogenous proviral genes (gs-chf-phenotype for group-specific antigens and chicken helper factor) that was common to all individuals studied. A tentative restriction has been derived for this and one other gs-chf-endogenous provirus. Other gs-chf-individuals and individuals with other phenotypes (e.g., gs+ chf+ and gsl chlfhE) showed more complicated patterns that often included additional bands and thus probably additional proviruses. RNA from an avian sarcoma virus was used to detect cellular sequences (sarc) homologous to the viral transforming gene (src). Results have revealed that a single restriction endonuclease EcoRI fragment of 13 x 10(6) daltons contains the majority of these sequences and confirm that they are not adjacent to the endogenous provirus.", "contents": "Structural studies on oncornavirus-related sequences in chicken genomic DNA: two-step analyses of EcoRI and Bgl I restriction digests and tentative mapping of a ubiquitous endogenous provirus digests and tentative mapping of a ubiquitous endogenous provirus. DNA from a variety of uninfected chicken cell types has been analyzed by using restriction endonuclease digestion and RPC-5 ion-exchange chromatography followed by agarose gel electrophoresis. Endogenous retrovirus sequences were detected by using a 32P-labeled avian leukosis viral RNA probe. One simple pattern was identified in an individual containing unexpressed endogenous proviral genes (gs-chf-phenotype for group-specific antigens and chicken helper factor) that was common to all individuals studied. A tentative restriction has been derived for this and one other gs-chf-endogenous provirus. Other gs-chf-individuals and individuals with other phenotypes (e.g., gs+ chf+ and gsl chlfhE) showed more complicated patterns that often included additional bands and thus probably additional proviruses. RNA from an avian sarcoma virus was used to detect cellular sequences (sarc) homologous to the viral transforming gene (src). Results have revealed that a single restriction endonuclease EcoRI fragment of 13 x 10(6) daltons contains the majority of these sequences and confirm that they are not adjacent to the endogenous provirus."}
{"id": "PMID:221918", "title": "Synthesis and use of 8-azidoguanosine 3',5'-cyclic monophosphate as photoaffinity label for cyclic GMP-dependent protein kinase.", "content": "8-Azidoguanosine 3',5'-cyclic monophosphate (8-N3cGMP) has been synthesized for use as a photoactive probe for the labeling of cGMP receptors. The ability of 8-N3cGMP to be bound at specific cGMP binding sites was demonstrated by its ability to activate cGMP-dependent protein kinase isolated from bovine lung (Ka = 1.1 x 10(-7) M) and to inhibit competitively the binding of [3H] cGMP to the enzyme [Kd (8 N3GMP)/Kd (cGMP) = 6]. Photolysis of 8-N3[32P]cGMP in the presence of a crude enzyme preparation resulted in the covalent attachment of analog to cGMP-dependent protein kinase. Half-maximal labeling occurred at 2.2 x 10(-7) M. The incorporation of the analog was completely inhibited by the addition of cGMP.", "contents": "Synthesis and use of 8-azidoguanosine 3',5'-cyclic monophosphate as photoaffinity label for cyclic GMP-dependent protein kinase. 8-Azidoguanosine 3',5'-cyclic monophosphate (8-N3cGMP) has been synthesized for use as a photoactive probe for the labeling of cGMP receptors. The ability of 8-N3cGMP to be bound at specific cGMP binding sites was demonstrated by its ability to activate cGMP-dependent protein kinase isolated from bovine lung (Ka = 1.1 x 10(-7) M) and to inhibit competitively the binding of [3H] cGMP to the enzyme [Kd (8 N3GMP)/Kd (cGMP) = 6]. Photolysis of 8-N3[32P]cGMP in the presence of a crude enzyme preparation resulted in the covalent attachment of analog to cGMP-dependent protein kinase. Half-maximal labeling occurred at 2.2 x 10(-7) M. The incorporation of the analog was completely inhibited by the addition of cGMP."}
{"id": "PMID:221919", "title": "Adenine nucleotide storage and secretion in platelets as studied by 31P nuclear magnetic resonance.", "content": "Suspensions of human and pig blood platelets have been studied by 31P NMR at 145.7 MHz and by chemical and radiochemical determination of nucleotide levels. In both types of platelets the cytoplasmic nucleotide pool, which was prelabeled by incubation with [14C]adenine, was selectively reduced by addition of H2O2/NaN3 or 2-deoxyglucose/antimycin A. After the reduction of cytoplasmic ATP in human platelets, the 31P NMR spectra showed an almost complete loss of the nucleoside di- and triphosphate resonances at temperatures examined (4--50 degrees C), indicating that only the cytoplasmic nucleotides had been observed, with no detectable contributions from the granular ATP, ADP, and pyrophosphate. Slow tumbling of the granular nucleotides, possibly due to aggregation, is the probable explanation of their undetectability at 145.7 MHz. Similar experiments showed that in pig platelets, granular ATP and ADP were not detected by 31P NMR at 4 degrees C but were observed at higher temperatures, indicating that aggregation may be occurring at the lower temperatures. Upon thrombin stimulation of human platelets, the NMR spectra and the chemical and radioactivity analyses showed that the granular adenylates and pyrophosphate were secreted, and that cytoplasmic ATP levels were appreciably reduced.", "contents": "Adenine nucleotide storage and secretion in platelets as studied by 31P nuclear magnetic resonance. Suspensions of human and pig blood platelets have been studied by 31P NMR at 145.7 MHz and by chemical and radiochemical determination of nucleotide levels. In both types of platelets the cytoplasmic nucleotide pool, which was prelabeled by incubation with [14C]adenine, was selectively reduced by addition of H2O2/NaN3 or 2-deoxyglucose/antimycin A. After the reduction of cytoplasmic ATP in human platelets, the 31P NMR spectra showed an almost complete loss of the nucleoside di- and triphosphate resonances at temperatures examined (4--50 degrees C), indicating that only the cytoplasmic nucleotides had been observed, with no detectable contributions from the granular ATP, ADP, and pyrophosphate. Slow tumbling of the granular nucleotides, possibly due to aggregation, is the probable explanation of their undetectability at 145.7 MHz. Similar experiments showed that in pig platelets, granular ATP and ADP were not detected by 31P NMR at 4 degrees C but were observed at higher temperatures, indicating that aggregation may be occurring at the lower temperatures. Upon thrombin stimulation of human platelets, the NMR spectra and the chemical and radioactivity analyses showed that the granular adenylates and pyrophosphate were secreted, and that cytoplasmic ATP levels were appreciably reduced."}
{"id": "PMID:221920", "title": "Preferential digestion of basement membrane collagen by an enzyme derived from a metastatic murine tumor.", "content": "The specificity of human skin collagenase and of an enzyme from an invasive tumor were studied by using types I, II, III, IV, and V (AB) collagen as substrates. Human skin collagenase degraded types I, II, and III collagen, producing the characteristic 3/4 and 1/4 cleavage products, but failed to degrade type IV or V collagen. Collagenase prepared from the invasive tumors showed maximal activity after trypsin treatment. The tumor enzyme degraded type IV (basement membrane) collagen, producing fragments consistent with a single cleavage site but did not attack types I, II, III, and V collagen. Because type IV collagen prepared by pepsinization of placenta was also digested, it is likely that cleavage of type IV collagen by the tumor collagenase occurs within a largely helical domain. A type IV collagenase could play a significant role in tumor metastases and in normal tissues where basement membrane turnover takes place.", "contents": "Preferential digestion of basement membrane collagen by an enzyme derived from a metastatic murine tumor. The specificity of human skin collagenase and of an enzyme from an invasive tumor were studied by using types I, II, III, IV, and V (AB) collagen as substrates. Human skin collagenase degraded types I, II, and III collagen, producing the characteristic 3/4 and 1/4 cleavage products, but failed to degrade type IV or V collagen. Collagenase prepared from the invasive tumors showed maximal activity after trypsin treatment. The tumor enzyme degraded type IV (basement membrane) collagen, producing fragments consistent with a single cleavage site but did not attack types I, II, III, and V collagen. Because type IV collagen prepared by pepsinization of placenta was also digested, it is likely that cleavage of type IV collagen by the tumor collagenase occurs within a largely helical domain. A type IV collagenase could play a significant role in tumor metastases and in normal tissues where basement membrane turnover takes place."}
{"id": "PMID:221921", "title": "Rate and equilibrium constants for binding of apo-E HDLc (a cholesterol-induced lipoprotein) and low density lipoproteins to human fibroblasts: evidence for multiple receptor binding of apo-E HDLc.", "content": "Competitive binding assays have demonstrated that a cholesterol-induced canine lipoprotein containing only the E apoprotein (apo-E HDL(c)) binds to the same cell surface receptors of human fibroblasts as human low density lipoproteins (LDL). However, the apo-E HDL(c) have a much greater binding activity than LDL. Equilibrium and kinetic binding studies were conducted at 4 degrees C to determine the mechanism for this enhanced receptor binding activity. Based on the data, the binding of both LDL and apo-E HDL(c) appears to be a simple bimolecular receptor interaction, and no heterogeneity of binding sites or cooperative effects among the receptor sites were observed. Equilibrium dissociation constants determined by Scatchard analysis of the equilibrium binding data for apo-E HDL(c) (K(d) = 0.12 x 10(-9) M) and LDL (K(d) = 2.8 x 10(-9) M) revealed a 23-fold greater affinity of HDL(c) for the receptors. Association and dissociation rate constants for the lipoprotein-receptor complex were determined from the time course of binding at various lipoprotein concentrations. The equilibrium dissociation constants calculated from these kinetic data confirmed that apo-E HDL(c) had a much higher affinity for the receptor than LDL. Furthermore, the kinetic studies indicated that apo-E HDL(c) bound more rapidly than LDL with rates of association of 18.0 x 10(4) and 5.5 x 10(4) M(-1) sec(-1), respectively. The rate of dissociation of the apo-E HDL(c)-receptor complex (1.7 x 10(-5) sec(-1)) was slower than that of the LDL receptor complex (6.3 x 10(-5) sec(-1)). An additional important difference between the binding of apo-E HDL(c) and LDL was that 4 times (3.6 +/- 0.4) as many LDL particles as HDL(c) particles were required for saturation of the receptors at maximal binding. These data indicate that each HDL(c) particle binds to multiple cell surface receptors at a ratio of 4:1 for LDL receptor binding.", "contents": "Rate and equilibrium constants for binding of apo-E HDLc (a cholesterol-induced lipoprotein) and low density lipoproteins to human fibroblasts: evidence for multiple receptor binding of apo-E HDLc. Competitive binding assays have demonstrated that a cholesterol-induced canine lipoprotein containing only the E apoprotein (apo-E HDL(c)) binds to the same cell surface receptors of human fibroblasts as human low density lipoproteins (LDL). However, the apo-E HDL(c) have a much greater binding activity than LDL. Equilibrium and kinetic binding studies were conducted at 4 degrees C to determine the mechanism for this enhanced receptor binding activity. Based on the data, the binding of both LDL and apo-E HDL(c) appears to be a simple bimolecular receptor interaction, and no heterogeneity of binding sites or cooperative effects among the receptor sites were observed. Equilibrium dissociation constants determined by Scatchard analysis of the equilibrium binding data for apo-E HDL(c) (K(d) = 0.12 x 10(-9) M) and LDL (K(d) = 2.8 x 10(-9) M) revealed a 23-fold greater affinity of HDL(c) for the receptors. Association and dissociation rate constants for the lipoprotein-receptor complex were determined from the time course of binding at various lipoprotein concentrations. The equilibrium dissociation constants calculated from these kinetic data confirmed that apo-E HDL(c) had a much higher affinity for the receptor than LDL. Furthermore, the kinetic studies indicated that apo-E HDL(c) bound more rapidly than LDL with rates of association of 18.0 x 10(4) and 5.5 x 10(4) M(-1) sec(-1), respectively. The rate of dissociation of the apo-E HDL(c)-receptor complex (1.7 x 10(-5) sec(-1)) was slower than that of the LDL receptor complex (6.3 x 10(-5) sec(-1)). An additional important difference between the binding of apo-E HDL(c) and LDL was that 4 times (3.6 +/- 0.4) as many LDL particles as HDL(c) particles were required for saturation of the receptors at maximal binding. These data indicate that each HDL(c) particle binds to multiple cell surface receptors at a ratio of 4:1 for LDL receptor binding."}
{"id": "PMID:221922", "title": "Detection by complementation of defective or uninducible (herpes simplex type 1) virus genomes latent in human ganglia.", "content": "Reconstruction experiments have shown that temperature-sensitive (ts) mutants of herpes simplex virus type 1 (HSV-1)(Glasgow strain 17) grow, complement, and recombine with similar efficiency in human nerve ganglion cells, human brain cells, normal human fibroblasts (WI38), and baby hamster kidney (BHK) 21/C13 hamster cells. Cultures of human trigeminal, superior cervical, and vagus ganglia that had failed to release herpes simplex virus spontaneously were superinfected with a range of ts mutants of HSV-1 and incubated at both permissive (31 degrees C) and nonpermissive (38.5 degrees C) temperatures. Progeny virus was assayed at both temperatures to determine if complementation of or recombination with the input genomes had occurred. The results showed that the ganglia from 8 of 14 individuals, which had been consistently negative for spontaneous release of virus, contained information that could be detected or rescued following superinfection with ts mutants of herpes simplex virus. In two additional cases, positive results were obtained after the superinfection of negative ganglia explants, but in each of these herpes simplex virus had previously been spontaneously released from one of six ganglia explanted.", "contents": "Detection by complementation of defective or uninducible (herpes simplex type 1) virus genomes latent in human ganglia. Reconstruction experiments have shown that temperature-sensitive (ts) mutants of herpes simplex virus type 1 (HSV-1)(Glasgow strain 17) grow, complement, and recombine with similar efficiency in human nerve ganglion cells, human brain cells, normal human fibroblasts (WI38), and baby hamster kidney (BHK) 21/C13 hamster cells. Cultures of human trigeminal, superior cervical, and vagus ganglia that had failed to release herpes simplex virus spontaneously were superinfected with a range of ts mutants of HSV-1 and incubated at both permissive (31 degrees C) and nonpermissive (38.5 degrees C) temperatures. Progeny virus was assayed at both temperatures to determine if complementation of or recombination with the input genomes had occurred. The results showed that the ganglia from 8 of 14 individuals, which had been consistently negative for spontaneous release of virus, contained information that could be detected or rescued following superinfection with ts mutants of herpes simplex virus. In two additional cases, positive results were obtained after the superinfection of negative ganglia explants, but in each of these herpes simplex virus had previously been spontaneously released from one of six ganglia explanted."}
{"id": "PMID:221923", "title": "Detection of a transformation-related antigen in chemically induced sarcomas and other transformed cells of the mouse.", "content": "Antisera prepared against BALB/c Meth A sarcoma in syngeneic or compatible F1 mice recognize a protein with an apparent molecular weight of 53,000 in extracts of [35S]methionine-labeled transformed BALB/c cells. This component, designated p53, was not detected in normal adult mouse fibroblasts, lymphoid cells, or hematopoietic cells or in mouse embryo cells or 3T3 cells. An extensive variety of antisera, including alloantisera and heterologous antisera directed against structural antigens of murine leukemia viruses, was tested for reactivity with p53; other than Meth A antisera, only comparably prepared antisera against another BALB/c sarcoma, CMS4, had anti-p53 activity. All transformed mouse cells tested were found to express p53; these tests included  chemically induced sarcomas, leukemias, spontaneously transformed fibroblasts, and cells transformed by simian virus 40 and murine sarcoma virus. The presence of p53 in tumors of no known viral etiology indicates coding by resident cellular genes; this does not exclude endogenous viruses as the source of coding sequences or the possibility that transforming viruses code directly for p53.", "contents": "Detection of a transformation-related antigen in chemically induced sarcomas and other transformed cells of the mouse. Antisera prepared against BALB/c Meth A sarcoma in syngeneic or compatible F1 mice recognize a protein with an apparent molecular weight of 53,000 in extracts of [35S]methionine-labeled transformed BALB/c cells. This component, designated p53, was not detected in normal adult mouse fibroblasts, lymphoid cells, or hematopoietic cells or in mouse embryo cells or 3T3 cells. An extensive variety of antisera, including alloantisera and heterologous antisera directed against structural antigens of murine leukemia viruses, was tested for reactivity with p53; other than Meth A antisera, only comparably prepared antisera against another BALB/c sarcoma, CMS4, had anti-p53 activity. All transformed mouse cells tested were found to express p53; these tests included  chemically induced sarcomas, leukemias, spontaneously transformed fibroblasts, and cells transformed by simian virus 40 and murine sarcoma virus. The presence of p53 in tumors of no known viral etiology indicates coding by resident cellular genes; this does not exclude endogenous viruses as the source of coding sequences or the possibility that transforming viruses code directly for p53."}
{"id": "PMID:221924", "title": "Biochemical basis for differential deoxyadenosine toxicity to T and B lymphoblasts: role for 5'-nucleotidase.", "content": "Deoxyadenosine metabolism was investigated in cultured human cells to elucidate the biochemical basis for the sensitivity of T lymphoblasts and the resistance of B lymphoblasts to deoxyadenosine toxicity. T lymphoblasts have a 20-to 45-fold greater capacity to synthesize deoxyadenosine nucleotides than B lymphoblasts at deoxyadenosine concentrations of 50--300 micron. During the synthesis of dATP, T lymphoblasts accumulate large quantities of dADP, whereas B lymphoblasts do not accumulate dADP. Enzymes affecting deoxyadenosine nucleotide synthesis were assayed in these cells. No substantial differences were evident in activities of deoxyadenosine kinase (ATP: deoxyadenosine 5'-phosphotransferase, EC 2.7.1.76) or deoxyadenylate kinase [ATP:(d)AMP phosphotransferase, EC 2.7.4.11]. The activity of 5'-nucleotidase (5'-ribonucleotide phosphohydrolase, EC 3.1.3.5) was increased 44-fold for AMP and 7-fold for dAMP in B lymphoblasts. A model for the regulation of deoxyadenosine nucleotide synthesis by 5'-nucleotidase activity is proposed on the basis of the observations.", "contents": "Biochemical basis for differential deoxyadenosine toxicity to T and B lymphoblasts: role for 5'-nucleotidase. Deoxyadenosine metabolism was investigated in cultured human cells to elucidate the biochemical basis for the sensitivity of T lymphoblasts and the resistance of B lymphoblasts to deoxyadenosine toxicity. T lymphoblasts have a 20-to 45-fold greater capacity to synthesize deoxyadenosine nucleotides than B lymphoblasts at deoxyadenosine concentrations of 50--300 micron. During the synthesis of dATP, T lymphoblasts accumulate large quantities of dADP, whereas B lymphoblasts do not accumulate dADP. Enzymes affecting deoxyadenosine nucleotide synthesis were assayed in these cells. No substantial differences were evident in activities of deoxyadenosine kinase (ATP: deoxyadenosine 5'-phosphotransferase, EC 2.7.1.76) or deoxyadenylate kinase [ATP:(d)AMP phosphotransferase, EC 2.7.4.11]. The activity of 5'-nucleotidase (5'-ribonucleotide phosphohydrolase, EC 3.1.3.5) was increased 44-fold for AMP and 7-fold for dAMP in B lymphoblasts. A model for the regulation of deoxyadenosine nucleotide synthesis by 5'-nucleotidase activity is proposed on the basis of the observations."}
{"id": "PMID:221925", "title": "Lymphoma development in mice and humans: diversity of initiation is followed by convergent cytogenetic evolution.", "content": "Human B cell lymphoma and murine T cell leukemia can be initiated by several agents. The present paper formulates some thoughts on the role of cytogenetic changes in the subsequent neoplastic process. Initiation creates long-lived preneoplastic cells. In some respects, they are comparable to in vitro-transformed (\"immortalized\") cell lines that maintain a diploid karyotype and are not tumorigenic in vivo. The development of a tumorigenic (\"autonomous\") clone is dependent on additional changes at the genetic level. In human B and murine T cell lymphoma, there are characteristic nonrandom chromosomal changes. The 14q+ marker appears to play a key role in human B cell lymphomas. The reciprocal 8;14 translocation in Burkitt lymphoma is a specialized subclass within this category. In murine T cell leukemia, trisomy 15 is the predominant change. The clustering of these nonrandom changes to tumors derived from a certain cell type rather than to tumors induced by a given etiological agent has important implications for the understanding of the genetic control of cellular responsiveness to growth-regulating forces in vivo.", "contents": "Lymphoma development in mice and humans: diversity of initiation is followed by convergent cytogenetic evolution. Human B cell lymphoma and murine T cell leukemia can be initiated by several agents. The present paper formulates some thoughts on the role of cytogenetic changes in the subsequent neoplastic process. Initiation creates long-lived preneoplastic cells. In some respects, they are comparable to in vitro-transformed (\"immortalized\") cell lines that maintain a diploid karyotype and are not tumorigenic in vivo. The development of a tumorigenic (\"autonomous\") clone is dependent on additional changes at the genetic level. In human B and murine T cell lymphoma, there are characteristic nonrandom chromosomal changes. The 14q+ marker appears to play a key role in human B cell lymphomas. The reciprocal 8;14 translocation in Burkitt lymphoma is a specialized subclass within this category. In murine T cell leukemia, trisomy 15 is the predominant change. The clustering of these nonrandom changes to tumors derived from a certain cell type rather than to tumors induced by a given etiological agent has important implications for the understanding of the genetic control of cellular responsiveness to growth-regulating forces in vivo."}
{"id": "PMID:221926", "title": "S-adenosylhomocysteine toxicity in normal and adenosine kinase-deficient lymphoblasts of human origin.", "content": "The human lymphoblast line WI-L2 is subject to growth inhibition by a combination of the adenosine deaminase (ADA; adenosine aminohydrolase, EC 3.5.4.4.) inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and adenosine. Although adenosine-induced pyrimidine starvation appears to contribute to this effect, uridine only partially reverses adenosine toxicity in WI-L2 and not at all in strain 107, an adenosine kinase-(ATP:adenosine 5'-phosphotransferase, EC 2.7.1.20) deficient derivative of WI-L2. Treatment of both cell lines with EHNA and adenosine leads to striking elevations in intracellular S-adenosyl-L-homocysteine (AdoHcy), a potent inhibitor of S-adenosyl-L-methionine (AdoMet)-dependent methylation reactions. The methylation in vivo of both DNA and RNA is inhibited by concentrations of EHNA and adenosine that elevate intracellular AdoHcy. Addition of 100 muM L-homocysteine thiolactone to cells treated with EHNA and adenosine enhances adenosine toxicity and further elevates AdoHcy to levels approximately 60-fold higher than those obtained in the absence of this amino acid, presumably by combining with adenosine to form AdoHcy in a reaction catalyzed by S-adenosylhomocysteine hydrolase (EC 3.3.1.1). In the adenosine kinase-deficient strain 107, a combination of ADA inhibition and L-homocysteine thiolactone markedly increases intracellular AdoHcy and inhibits growth even in the absence of exogenous adenosine. These results demonstrate a form of toxicity from endogenously produced adenosine and support the view that AdoHcy, by inhibiting methylation, is a mediator of uridine-resistant adenosine toxicity in these human lymphoblast lines. Furthermore, they suggest that AdoHcy may play a role in the pathogenesis of the severe combined immunodeficiency disease found in most children with heritable ADA deficiency.", "contents": "S-adenosylhomocysteine toxicity in normal and adenosine kinase-deficient lymphoblasts of human origin. The human lymphoblast line WI-L2 is subject to growth inhibition by a combination of the adenosine deaminase (ADA; adenosine aminohydrolase, EC 3.5.4.4.) inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and adenosine. Although adenosine-induced pyrimidine starvation appears to contribute to this effect, uridine only partially reverses adenosine toxicity in WI-L2 and not at all in strain 107, an adenosine kinase-(ATP:adenosine 5'-phosphotransferase, EC 2.7.1.20) deficient derivative of WI-L2. Treatment of both cell lines with EHNA and adenosine leads to striking elevations in intracellular S-adenosyl-L-homocysteine (AdoHcy), a potent inhibitor of S-adenosyl-L-methionine (AdoMet)-dependent methylation reactions. The methylation in vivo of both DNA and RNA is inhibited by concentrations of EHNA and adenosine that elevate intracellular AdoHcy. Addition of 100 muM L-homocysteine thiolactone to cells treated with EHNA and adenosine enhances adenosine toxicity and further elevates AdoHcy to levels approximately 60-fold higher than those obtained in the absence of this amino acid, presumably by combining with adenosine to form AdoHcy in a reaction catalyzed by S-adenosylhomocysteine hydrolase (EC 3.3.1.1). In the adenosine kinase-deficient strain 107, a combination of ADA inhibition and L-homocysteine thiolactone markedly increases intracellular AdoHcy and inhibits growth even in the absence of exogenous adenosine. These results demonstrate a form of toxicity from endogenously produced adenosine and support the view that AdoHcy, by inhibiting methylation, is a mediator of uridine-resistant adenosine toxicity in these human lymphoblast lines. Furthermore, they suggest that AdoHcy may play a role in the pathogenesis of the severe combined immunodeficiency disease found in most children with heritable ADA deficiency."}
{"id": "PMID:221927", "title": "Integration of different sarcoma virus genomes into host DNA: evidence against tandem arrangement and for shared integration sites.", "content": "Cellular DNA of 50--54 S was extracted from chicken embryo cells doubly infected with two different avian sarcoma viruses and was analyzed by the infectious DNA assay. Approximately 80--90% of the transformed foci that were induced by this DNA were found to give rise to one kind of avian sarcoma virus only, indicating that most proviral genomes are not integrated in tandem. When the two infecting viruses were varied with respect to multiplicity or time of infection, the initial infecting virus or the virus of higher multiplicity of infection was recovered at higher frequency in foci produced by the extracted DNA. This observation suggests that existence of common integration sites for different avian sarcoma viruses. Cells uniformly infected with avian leukosis virus could be transformed by superinfection with an avian sarcoma virus from a different envelope subgroup. Infectious DNA recovered from such cells contained 3--10 50% infectious dose (ID50) units of leukosis virus per microgram but only 0.3--0.4 ID50 of sarcoma virus. DNA from cells infected with sarcoma virus alone contained 3 sarcoma virus ID50 per microgram. These results suggest that, even though a second virus integrates with lower efficiency into preinfected cells, there is not a complete block of integration sites by the first virus.", "contents": "Integration of different sarcoma virus genomes into host DNA: evidence against tandem arrangement and for shared integration sites. Cellular DNA of 50--54 S was extracted from chicken embryo cells doubly infected with two different avian sarcoma viruses and was analyzed by the infectious DNA assay. Approximately 80--90% of the transformed foci that were induced by this DNA were found to give rise to one kind of avian sarcoma virus only, indicating that most proviral genomes are not integrated in tandem. When the two infecting viruses were varied with respect to multiplicity or time of infection, the initial infecting virus or the virus of higher multiplicity of infection was recovered at higher frequency in foci produced by the extracted DNA. This observation suggests that existence of common integration sites for different avian sarcoma viruses. Cells uniformly infected with avian leukosis virus could be transformed by superinfection with an avian sarcoma virus from a different envelope subgroup. Infectious DNA recovered from such cells contained 3--10 50% infectious dose (ID50) units of leukosis virus per microgram but only 0.3--0.4 ID50 of sarcoma virus. DNA from cells infected with sarcoma virus alone contained 3 sarcoma virus ID50 per microgram. These results suggest that, even though a second virus integrates with lower efficiency into preinfected cells, there is not a complete block of integration sites by the first virus."}
{"id": "PMID:221928", "title": "Ca2+ and cyclic AMP regulate phosphorylation of same two membrane-associated proteins specific to nerve tissue.", "content": "It was shown previously that addition of cyclic AMP (cAMP) to a synaptic membrane fraction incubated with [gamma-32P]ATP stimulated the phosphorylation of two proteins, designated proteins Ia and Ib, found only in nerve tissue. Addition of Ca2+ plus veratridine to synaptosomes preincubated with 32Pi stimulated the phosphorylation of two proteins with similar apparent molecular weights. Various techniques have now been used to determine whether the two proteins phosphorylated in synaptosomes in the presence of Ca2+ plus veratridine are the same as proteins Ia and Ib phosphorylated in synaptic membranes in the presence of cAMP. The proteins phosphorylated by the two procedures were extracted under similar conditions, had similar apparent molecular weights and charges, and were digested by collagenase at similar rates and to the same radioactive intermediates and end products. Furthermore, the two sets of proteins were digested by three other proteolytic enzymes to phosphopeptides with similar molecular weights. The results indicate that Ca2+ and cAMP are each capable of regulating the phosphorylation of proteins Ia and Ib.", "contents": "Ca2+ and cyclic AMP regulate phosphorylation of same two membrane-associated proteins specific to nerve tissue. It was shown previously that addition of cyclic AMP (cAMP) to a synaptic membrane fraction incubated with [gamma-32P]ATP stimulated the phosphorylation of two proteins, designated proteins Ia and Ib, found only in nerve tissue. Addition of Ca2+ plus veratridine to synaptosomes preincubated with 32Pi stimulated the phosphorylation of two proteins with similar apparent molecular weights. Various techniques have now been used to determine whether the two proteins phosphorylated in synaptosomes in the presence of Ca2+ plus veratridine are the same as proteins Ia and Ib phosphorylated in synaptic membranes in the presence of cAMP. The proteins phosphorylated by the two procedures were extracted under similar conditions, had similar apparent molecular weights and charges, and were digested by collagenase at similar rates and to the same radioactive intermediates and end products. Furthermore, the two sets of proteins were digested by three other proteolytic enzymes to phosphopeptides with similar molecular weights. The results indicate that Ca2+ and cAMP are each capable of regulating the phosphorylation of proteins Ia and Ib."}
{"id": "PMID:221940", "title": "ACTH self-administration in rats.", "content": "The ability of rats to learn a lever pressing response reinforced by a contingent intravenous delivery of ACTH 1--24 and 4--10, was investigated. About 60% of the rats tested learned to press the lever for the two analogues that were infused at a rate of 2.08 microgram per second via a chronically implanted intrajugular catheter. Most of the animals exhibited sustained daily self-injections of 250 to 375 microgram of ACTH 1--24 and more variable amounts of ACTH 4--10. Comparisons with the self-administration of saline and altered responses following a change in the concentration of ACTH 1--24 solution indicated a positively reinforcing effect for the neuropeptide. The self-administration of the ACTH 4--10 analogue demonstrates that this reinforcing property of ACTH is not due to its adrenal stimulating activity. Brain targets possibly involved in the self-administration of ACTH are discussed.", "contents": "ACTH self-administration in rats. The ability of rats to learn a lever pressing response reinforced by a contingent intravenous delivery of ACTH 1--24 and 4--10, was investigated. About 60% of the rats tested learned to press the lever for the two analogues that were infused at a rate of 2.08 microgram per second via a chronically implanted intrajugular catheter. Most of the animals exhibited sustained daily self-injections of 250 to 375 microgram of ACTH 1--24 and more variable amounts of ACTH 4--10. Comparisons with the self-administration of saline and altered responses following a change in the concentration of ACTH 1--24 solution indicated a positively reinforcing effect for the neuropeptide. The self-administration of the ACTH 4--10 analogue demonstrates that this reinforcing property of ACTH is not due to its adrenal stimulating activity. Brain targets possibly involved in the self-administration of ACTH are discussed."}
{"id": "PMID:221941", "title": "The influence of mouse genotype on the changes in brain cyclic nucleotide levels induced by acute alcohol administration.", "content": "Two mouse strains (C57BL/6By and BALB/cByJ) were found to differ widely in their sleep-time response to ethanol (3 g/kg), but showed no difference in their hypothermic response to the same ethanol dose. Comparison of brain cyclic nucleotide levels in the two strains revealed a strain difference in the brain cyclic AMP response to ethanol but no strain difference in the magnitude of the brain cyclic GMP change. Alcohol produced a significant drop in cerebellar cyclic GMP in both strains, and a decrease in cerebellar cyclic AMP in C57BL/6By mice. The cyclic AMP/cyclic GMP ratio increased following alcohol in the cerebellum of BALB/cByJ mice but not C57BL/6By mice. The results are discussed in terms of possible relationships between alcohol-induced changes in neurochemistry and behavior.", "contents": "The influence of mouse genotype on the changes in brain cyclic nucleotide levels induced by acute alcohol administration. Two mouse strains (C57BL/6By and BALB/cByJ) were found to differ widely in their sleep-time response to ethanol (3 g/kg), but showed no difference in their hypothermic response to the same ethanol dose. Comparison of brain cyclic nucleotide levels in the two strains revealed a strain difference in the brain cyclic AMP response to ethanol but no strain difference in the magnitude of the brain cyclic GMP change. Alcohol produced a significant drop in cerebellar cyclic GMP in both strains, and a decrease in cerebellar cyclic AMP in C57BL/6By mice. The cyclic AMP/cyclic GMP ratio increased following alcohol in the cerebellum of BALB/cByJ mice but not C57BL/6By mice. The results are discussed in terms of possible relationships between alcohol-induced changes in neurochemistry and behavior."}
{"id": "PMID:221942", "title": "[The antiviral activity of performic acid (author's transl)].", "content": "Under the experimental conditions chosen by the authors, it was demonstrated that the antiviral activity of performic acid against Coxsackie virus B 1 is greater than that of peracetic acid.", "contents": "[The antiviral activity of performic acid (author's transl)]. Under the experimental conditions chosen by the authors, it was demonstrated that the antiviral activity of performic acid against Coxsackie virus B 1 is greater than that of peracetic acid."}
{"id": "PMID:221943", "title": "Effects of ACTH-like neuropeptides on animal behavior and man.", "content": "In this review the behavioral effects of neuropeptides related to ACTH have been considered and evidence concerning their mechanism of action in animal and man are briefly presented. Psychoactive properties of these neuropeptides manifest themselves in enhancing motivation, attention, learning and memory processes. The application of these peptides in the mentally ill awaits further exploration.", "contents": "Effects of ACTH-like neuropeptides on animal behavior and man. In this review the behavioral effects of neuropeptides related to ACTH have been considered and evidence concerning their mechanism of action in animal and man are briefly presented. Psychoactive properties of these neuropeptides manifest themselves in enhancing motivation, attention, learning and memory processes. The application of these peptides in the mentally ill awaits further exploration."}
{"id": "PMID:221944", "title": "Cyclic adenosine 3',5'-monophosphate in rat cerebral cortical slices: effects of methoxamine and clonidine.", "content": "In incubated slices of cerebral cortex from Sprague-Dawley rats, methoxamine and clonidine have no effect on basal levels of cyclic AMP. Methoxamine effectively inhibits the noradrenaline-stimulated formation of cyclic AMP. The inhibitory constant for methoxamine was 12.6 mumol/l. In the presence of 100 mumol/l adenosine, methoxamine does not inhibit the activity of noradrenaline, but is capable to activate alpha-adrenergic receptors leading to enhanced formation of cyclic AMP. The mechanism by which adenosine alters adrenergic receptors to become methoxamine-sensitive is not known. Clonidine inhibits the effect of noradrenaline alone or in combination with adenosine on the cyclic-AMP-generating system. It does not, as reported earlier, enhance the activity of submaximal concentrations of the beta-adrenergic agonist isoproterenol. These data do not support the concept of adrenergic receptors which require both, alpha- and beta-stimulation for maximal activation of adenylate cyclase.", "contents": "Cyclic adenosine 3',5'-monophosphate in rat cerebral cortical slices: effects of methoxamine and clonidine. In incubated slices of cerebral cortex from Sprague-Dawley rats, methoxamine and clonidine have no effect on basal levels of cyclic AMP. Methoxamine effectively inhibits the noradrenaline-stimulated formation of cyclic AMP. The inhibitory constant for methoxamine was 12.6 mumol/l. In the presence of 100 mumol/l adenosine, methoxamine does not inhibit the activity of noradrenaline, but is capable to activate alpha-adrenergic receptors leading to enhanced formation of cyclic AMP. The mechanism by which adenosine alters adrenergic receptors to become methoxamine-sensitive is not known. Clonidine inhibits the effect of noradrenaline alone or in combination with adenosine on the cyclic-AMP-generating system. It does not, as reported earlier, enhance the activity of submaximal concentrations of the beta-adrenergic agonist isoproterenol. These data do not support the concept of adrenergic receptors which require both, alpha- and beta-stimulation for maximal activation of adenylate cyclase."}
{"id": "PMID:221946", "title": "Paramagnetic changes during development of DMBA-induced mammary tumours in Sprague-Dawley rats.", "content": "Paramagnetic changes occurring during development of mammary tumours in Sprague--Dawley rats induced by the chemical DMBA were studied using electron spin resonance. A two-fold increase in free-radical signal intensity was observed at the time of appearance of the tumour. The free radical concentration remained elevated to this level throughout the experiment. This change is different from the gradual decrease reported for frozen ESR samples in other experimental tumour systems and from the pattern reported for lyophilised samples. A gradual increase in the concentration of Mn2+ was also observed. A high frequency (35 GHz) ESR spectrometer was used which enabled us to study the small amount of tissue available from small tumours and normal breast tissue. Quantitative histological analysis of the samples after ESR study indicated that the ESR signal in the normal tissues could not be attributed to any particular cell type, including glandular cells. The increase observed in the tumour appeared to be due to an increased concentration of paramagnetic species in the tumour cells. Most of the tumours were adenocarcinomas but several benign adenomas were also observed. The ESR signals in the benign tumours were indistinguishable from those of the malignant tumours.", "contents": "Paramagnetic changes during development of DMBA-induced mammary tumours in Sprague-Dawley rats. Paramagnetic changes occurring during development of mammary tumours in Sprague--Dawley rats induced by the chemical DMBA were studied using electron spin resonance. A two-fold increase in free-radical signal intensity was observed at the time of appearance of the tumour. The free radical concentration remained elevated to this level throughout the experiment. This change is different from the gradual decrease reported for frozen ESR samples in other experimental tumour systems and from the pattern reported for lyophilised samples. A gradual increase in the concentration of Mn2+ was also observed. A high frequency (35 GHz) ESR spectrometer was used which enabled us to study the small amount of tissue available from small tumours and normal breast tissue. Quantitative histological analysis of the samples after ESR study indicated that the ESR signal in the normal tissues could not be attributed to any particular cell type, including glandular cells. The increase observed in the tumour appeared to be due to an increased concentration of paramagnetic species in the tumour cells. Most of the tumours were adenocarcinomas but several benign adenomas were also observed. The ESR signals in the benign tumours were indistinguishable from those of the malignant tumours."}
{"id": "PMID:221952", "title": "The spinal origin of the sympathetic nerve fibres to the vascular and secretory components of the rat submaxillary salivary gland.", "content": "The spinal origin of the sympathetic vasoconstrictor and secretory fibres to the submaxillary gland of the rat was identified in the pithed rat preparation by means of selective stimulation of small segments of the spinal outflow. Secretory and vascular responses were similar following stimulation in pithed rats to those following stimulation of the isolated superior cervical nerve trunk in anaesthetized rats. The spinal origin of the secretory and vascular fibres was coincident and it is concluded that if a separate control of blood flow and secretion by sympathetic fibres does exist that it must occur at the level of C.N.S. but that the nerves share a common pathway to the gland.", "contents": "The spinal origin of the sympathetic nerve fibres to the vascular and secretory components of the rat submaxillary salivary gland. The spinal origin of the sympathetic vasoconstrictor and secretory fibres to the submaxillary gland of the rat was identified in the pithed rat preparation by means of selective stimulation of small segments of the spinal outflow. Secretory and vascular responses were similar following stimulation in pithed rats to those following stimulation of the isolated superior cervical nerve trunk in anaesthetized rats. The spinal origin of the secretory and vascular fibres was coincident and it is concluded that if a separate control of blood flow and secretion by sympathetic fibres does exist that it must occur at the level of C.N.S. but that the nerves share a common pathway to the gland."}
{"id": "PMID:221964", "title": "Restrictions on the applicability of mixed ligand chelate therapy (MLC) in acute cadmium intoxication.", "content": "An experimental study of the comparative effectiveness of single and mixed ligand chelates as antidotes for acute cadmium poisoning reveals few appreciable differences when the cadmium (as cadmium chloride or acetate) is administered ip. In each case the mixed ligand chelate system showed little or no improvement over the results obtained with the most effective of the individual components. This procedure, using mixed ligand chelate systems, may well be one which is limited to conditions more narrowly similar to those reported by Schubert and Derr (1978). It does not appear to possess the broad range of applicability which might be expected from the equilibrium principles on which it is based. By comparing our data with previous studies it can be seen that Na2CaEDTA is capable of offsetting the lethality of ip cadmium chloride when the latter is administered at rather higher levels that have previously been counteracted by any of the sulfur containing chelating agents tested to date.", "contents": "Restrictions on the applicability of mixed ligand chelate therapy (MLC) in acute cadmium intoxication. An experimental study of the comparative effectiveness of single and mixed ligand chelates as antidotes for acute cadmium poisoning reveals few appreciable differences when the cadmium (as cadmium chloride or acetate) is administered ip. In each case the mixed ligand chelate system showed little or no improvement over the results obtained with the most effective of the individual components. This procedure, using mixed ligand chelate systems, may well be one which is limited to conditions more narrowly similar to those reported by Schubert and Derr (1978). It does not appear to possess the broad range of applicability which might be expected from the equilibrium principles on which it is based. By comparing our data with previous studies it can be seen that Na2CaEDTA is capable of offsetting the lethality of ip cadmium chloride when the latter is administered at rather higher levels that have previously been counteracted by any of the sulfur containing chelating agents tested to date."}
{"id": "PMID:221965", "title": "Sleep state effects on breathing after spinal cord transection and vagotomy in the cat.", "content": "The role of chest wall and vagal afferents on breathing during wakefulness (W), nonrapid eye movement sleep (NREM), and REM sleep was assessed in 16 adult cats implanted with electrodes and skull bolts for sleep recordings with head restraint. Breathing was monitored with a pneumotachograph. Following control recordings establishing characteristic respiratory patterns during each state, cats sustained spinal cord transections at T-1, vagotomies, or both. The transections decreased variability of breathing rate, while vagotomies decreased rate but increased variability and tidal volume. These deafferentations alone or in combination failed to eliminate the major effects of state upon breathing pattern. Different states of consciousness were associated with significant changes on every measured breathing parameter, but the interactions of these effects with the deafferentations were small or nonsignificant. The vagus, however, appears to play its largest role during NREM. We hypothesize that while vagal afference functions during all states to terminate inspiration, during W and REM separate but functionally equivalent mechanisms of central origin supplement the vagus in facilitating the termination of inspiration. The absence of these mechanisms during NREM accounts for the increased vagal influence during this state.", "contents": "Sleep state effects on breathing after spinal cord transection and vagotomy in the cat. The role of chest wall and vagal afferents on breathing during wakefulness (W), nonrapid eye movement sleep (NREM), and REM sleep was assessed in 16 adult cats implanted with electrodes and skull bolts for sleep recordings with head restraint. Breathing was monitored with a pneumotachograph. Following control recordings establishing characteristic respiratory patterns during each state, cats sustained spinal cord transections at T-1, vagotomies, or both. The transections decreased variability of breathing rate, while vagotomies decreased rate but increased variability and tidal volume. These deafferentations alone or in combination failed to eliminate the major effects of state upon breathing pattern. Different states of consciousness were associated with significant changes on every measured breathing parameter, but the interactions of these effects with the deafferentations were small or nonsignificant. The vagus, however, appears to play its largest role during NREM. We hypothesize that while vagal afference functions during all states to terminate inspiration, during W and REM separate but functionally equivalent mechanisms of central origin supplement the vagus in facilitating the termination of inspiration. The absence of these mechanisms during NREM accounts for the increased vagal influence during this state."}
{"id": "PMID:221968", "title": "Considerations on early surgery in the treatment of extensive burns.", "content": "The results obtained with early surgical treatment of burns have been re-examined from various aspects. Early escharectomy, which tranforms the necrobiotic tissue into a surgical lesion, reduces the chemical factors of inflammation, lowers the lactic acid level and depresses the activity and disordered proliferation of the fibroblasts and the consequent laying down of immature collagen which is responsible for the pathological evolution of the burn scar. The removal of toxic material with proteasic activity, the reduction in the risk of sepsis, the saving of work for the immunopoietic mechanism, a reduction in the weight loss through improved nitrogen balance and an increase in the anabolic phase of muscular metabolism by early movement as well as a shortening of the period of hospitalization--all are factors in favour of the early surgical technique. Better healing is obtained by the elimination of the necrotic tissue, a reduction in the haematologic tissue inflammation mediators, an increase in the antibacterial defence following the reconstruction of the skin surface with covering materials and the rapid articular reduction; not to mention the inhibition of the formation of granulation tissue.", "contents": "Considerations on early surgery in the treatment of extensive burns. The results obtained with early surgical treatment of burns have been re-examined from various aspects. Early escharectomy, which tranforms the necrobiotic tissue into a surgical lesion, reduces the chemical factors of inflammation, lowers the lactic acid level and depresses the activity and disordered proliferation of the fibroblasts and the consequent laying down of immature collagen which is responsible for the pathological evolution of the burn scar. The removal of toxic material with proteasic activity, the reduction in the risk of sepsis, the saving of work for the immunopoietic mechanism, a reduction in the weight loss through improved nitrogen balance and an increase in the anabolic phase of muscular metabolism by early movement as well as a shortening of the period of hospitalization--all are factors in favour of the early surgical technique. Better healing is obtained by the elimination of the necrotic tissue, a reduction in the haematologic tissue inflammation mediators, an increase in the antibacterial defence following the reconstruction of the skin surface with covering materials and the rapid articular reduction; not to mention the inhibition of the formation of granulation tissue."}
{"id": "PMID:221969", "title": "Endocrine response after burn.", "content": "The use of radioimmunoassays has made new advances in post-burn endocrine studies possible. The mean fasting IRI plasma (pl.) levels were elevated for 7 weeks, sometimes reaching very high values. During OGTT, an impaired glucose tolerance and insulin resistance could be found. Pl. HGH levels were normal or slightly increased, and their hypoglycemia-caused rise in the first two postburn weeks was blocked. Renin and Angiotensin II pl. levels were high or very high in almost all burned patients. They were very sensitive indicators of burn stress. ACTH pl. levels were in some respects unpredictable: sometimes very high, sometimes only moderately elevated, or normal. There was mostly no correlation between them and the respective 17-OHCS. Serum FSH was uniformly low or very low, while LH was high (25%), normal (31%) or low (44%). Pl. testosterone levels were uniformly very low, except for the first 1-2 postburn days, even in minor burns, their levels returning to normal during convalescence. The response after chorionic gonadotropin was similar. This severe peripheric endocrine gland involvement (burn toxins? impaired circulation?) could be found to some extent when T4 (thyroxine) levels in serum were measured, especially during TSH tests. There was no correlation between TSH and T4 values. The pituitary response (LH, TSH, less FSH) to TRF and LHRH was normal in all patients tested. All the above can have far reaching endocrine and metabolic consequences (catabolism, fuel supply, endocrine priorities), with many new research and therapeutic possibilities.", "contents": "Endocrine response after burn. The use of radioimmunoassays has made new advances in post-burn endocrine studies possible. The mean fasting IRI plasma (pl.) levels were elevated for 7 weeks, sometimes reaching very high values. During OGTT, an impaired glucose tolerance and insulin resistance could be found. Pl. HGH levels were normal or slightly increased, and their hypoglycemia-caused rise in the first two postburn weeks was blocked. Renin and Angiotensin II pl. levels were high or very high in almost all burned patients. They were very sensitive indicators of burn stress. ACTH pl. levels were in some respects unpredictable: sometimes very high, sometimes only moderately elevated, or normal. There was mostly no correlation between them and the respective 17-OHCS. Serum FSH was uniformly low or very low, while LH was high (25%), normal (31%) or low (44%). Pl. testosterone levels were uniformly very low, except for the first 1-2 postburn days, even in minor burns, their levels returning to normal during convalescence. The response after chorionic gonadotropin was similar. This severe peripheric endocrine gland involvement (burn toxins? impaired circulation?) could be found to some extent when T4 (thyroxine) levels in serum were measured, especially during TSH tests. There was no correlation between TSH and T4 values. The pituitary response (LH, TSH, less FSH) to TRF and LHRH was normal in all patients tested. All the above can have far reaching endocrine and metabolic consequences (catabolism, fuel supply, endocrine priorities), with many new research and therapeutic possibilities."}
{"id": "PMID:221970", "title": "Cyclic nucleotides in joint fluid in rheumatoid arthritis and in Reiter's syndrome.", "content": "Levels of cyclic adenosine 3',5'-monophosphate (cAMP) and cyclic guanosine 3',5'-monophosphate (cGMP) have been investigated in joint fluid in inflammatory arthropathies. A disturbed balance between cAMP and cGMP due to a depressed level of cAMP was found in rheumatoid arthritis (RA) and Reiter's syndrome, in comparison with patients with osteoarthritis. No correlation could be demonstrated between the absolute levels of cAMP or cGMP and the degree of local inflammatory activity, white cell count, or lysosomal enzyme activity in the joint fluid. Intra-articular injection of epinephrine showed just as good an effect on local pain as betamethasone (Cellestona), but the steriod reduced the swelling more effectively. An increase in intracellular levels of cAMP at 20 min was observed following injection of epinephrine with a slight change in cGMP. Intra-articular injection of dibutyryl-cAMP (db-cAMP) produced a marked easing of local pain and swelling in each of the 4 patients so treated. It is concluded that stimulation of the beta-adrenergic system or injection with db-cAMP may be beneficial in rheumatoid inflammation.", "contents": "Cyclic nucleotides in joint fluid in rheumatoid arthritis and in Reiter's syndrome. Levels of cyclic adenosine 3',5'-monophosphate (cAMP) and cyclic guanosine 3',5'-monophosphate (cGMP) have been investigated in joint fluid in inflammatory arthropathies. A disturbed balance between cAMP and cGMP due to a depressed level of cAMP was found in rheumatoid arthritis (RA) and Reiter's syndrome, in comparison with patients with osteoarthritis. No correlation could be demonstrated between the absolute levels of cAMP or cGMP and the degree of local inflammatory activity, white cell count, or lysosomal enzyme activity in the joint fluid. Intra-articular injection of epinephrine showed just as good an effect on local pain as betamethasone (Cellestona), but the steriod reduced the swelling more effectively. An increase in intracellular levels of cAMP at 20 min was observed following injection of epinephrine with a slight change in cGMP. Intra-articular injection of dibutyryl-cAMP (db-cAMP) produced a marked easing of local pain and swelling in each of the 4 patients so treated. It is concluded that stimulation of the beta-adrenergic system or injection with db-cAMP may be beneficial in rheumatoid inflammation."}
{"id": "PMID:221967", "title": "[Accumulation of glutamic acid and glycine in human cerebral tumors in vitro].", "content": "Preliminary results are given on transport of glycine and L-glutamate into human cerebral tissue, normal and tumoral. In comparison with normal tissue, glycine transport is diminished in meningioma and oligodendroblastoma, unaffected in neurinoma, sharply increased in medulloblastoma. Glutamic acid transport is lowered in neurinoma and oligodendroblastoma; increased in medulloblastoma. Such preliminary observations are briefly discussed.", "contents": "[Accumulation of glutamic acid and glycine in human cerebral tumors in vitro]. Preliminary results are given on transport of glycine and L-glutamate into human cerebral tissue, normal and tumoral. In comparison with normal tissue, glycine transport is diminished in meningioma and oligodendroblastoma, unaffected in neurinoma, sharply increased in medulloblastoma. Glutamic acid transport is lowered in neurinoma and oligodendroblastoma; increased in medulloblastoma. Such preliminary observations are briefly discussed."}
{"id": "PMID:221972", "title": "Oxytocin receptors: triggers for parturition and lactation?", "content": "Specific binding of tritiated oxytocin to uterine receptors of pregnant rats increases dramatically at term and is maximal during labor. In mammary glands the increase in binding is gradual, reaching a maximum during the lactation period. Concomitant changes in the sensitivity of the uterus and mammary gland to oxytocin indicate that the receptor concentration is of functional significance. Oxytocin receptors, therefore, may regulate the response of the target organs to circulating oxytocin and thereby control the onset of labor and lactation. Ovarian steroids participate in the regulation of oxytocin receptors in a manner as yet unclarified.", "contents": "Oxytocin receptors: triggers for parturition and lactation? Specific binding of tritiated oxytocin to uterine receptors of pregnant rats increases dramatically at term and is maximal during labor. In mammary glands the increase in binding is gradual, reaching a maximum during the lactation period. Concomitant changes in the sensitivity of the uterus and mammary gland to oxytocin indicate that the receptor concentration is of functional significance. Oxytocin receptors, therefore, may regulate the response of the target organs to circulating oxytocin and thereby control the onset of labor and lactation. Ovarian steroids participate in the regulation of oxytocin receptors in a manner as yet unclarified."}
{"id": "PMID:221973", "title": "ACTH and vasopressin treatments immediately after a defeat increase future submissiveness in male mice.", "content": "Male mice were given a single injection of either adrenocorticotropic hormone (ACTH) or lysine vasopressin immediately after a defeat in an encounter with an aggressive male mouse. The defeated mice were tested for submissiveness at either 24 hours, 48 hours, or 7 days after the initial encounter. Both hormone treatments increased future submissiveness, although the time courses of the effects were different: The effects of ACTH disappeared after 48 hours, whereas those of vasopressin persisted for 7 days. These results suggest that changes in peptide hormone levels following naturally stressful experiences can affect the memory of those experiences, as expressed in future adaptive responses.", "contents": "ACTH and vasopressin treatments immediately after a defeat increase future submissiveness in male mice. Male mice were given a single injection of either adrenocorticotropic hormone (ACTH) or lysine vasopressin immediately after a defeat in an encounter with an aggressive male mouse. The defeated mice were tested for submissiveness at either 24 hours, 48 hours, or 7 days after the initial encounter. Both hormone treatments increased future submissiveness, although the time courses of the effects were different: The effects of ACTH disappeared after 48 hours, whereas those of vasopressin persisted for 7 days. These results suggest that changes in peptide hormone levels following naturally stressful experiences can affect the memory of those experiences, as expressed in future adaptive responses."}
{"id": "PMID:221974", "title": "Sleep and estivation (shallow torpor): continuous processes of energy conservation.", "content": "Estivation (shallow torpor) in the round-tailed ground squirrel (Citellus tereticaudus) is entered through electrophysiologically defined states of sleep. Rapid-eye-movement sleep diminishes as body temperature falls in such a way that, at a body temperature of 26 degrees to 28 degrees C, torpor is characterized by almost continuous slow-wave sleep isomorphic with that observed at euthermic body temperatures.", "contents": "Sleep and estivation (shallow torpor): continuous processes of energy conservation. Estivation (shallow torpor) in the round-tailed ground squirrel (Citellus tereticaudus) is entered through electrophysiologically defined states of sleep. Rapid-eye-movement sleep diminishes as body temperature falls in such a way that, at a body temperature of 26 degrees to 28 degrees C, torpor is characterized by almost continuous slow-wave sleep isomorphic with that observed at euthermic body temperatures."}
{"id": "PMID:221975", "title": "Morphogenesis in dictyostelium: an orbital hypothesis.", "content": "Free-living amoebae of Dictyostelium discoideum aggregate when deprived food, guided by the intercellular transmission of signals of adenosine 3',5'-monophosphate. A succession of multicellular forms is then constructed, each with a circular cross section in every plane normal to its central axis. Amoebae are in constant circular and helical motion around the circumference of these structures. A theory is proposed wherein the sustained progagation of waves of cyclic adenosine 3',5'-monophosphate secretion in cellular loops determines their circumference and thereby organizes morphogenesis in this organism.", "contents": "Morphogenesis in dictyostelium: an orbital hypothesis. Free-living amoebae of Dictyostelium discoideum aggregate when deprived food, guided by the intercellular transmission of signals of adenosine 3',5'-monophosphate. A succession of multicellular forms is then constructed, each with a circular cross section in every plane normal to its central axis. Amoebae are in constant circular and helical motion around the circumference of these structures. A theory is proposed wherein the sustained progagation of waves of cyclic adenosine 3',5'-monophosphate secretion in cellular loops determines their circumference and thereby organizes morphogenesis in this organism."}
{"id": "PMID:221977", "title": "Phospholipid methylation unmasks cryptic beta-adrenergic receptors in rat reticulocytes.", "content": "The effect of phospholipid methylation on the number of beta-adrenergic receptor binding sites was examined in rat reticulocyte membranes. Stimulation of phosphatidylcholine synthesis by the introduction of the methyl donor S-adenosyl-L-methionine into reticulocyte ghosts increased the number of beta-adrenergic receptor sites. The appearance of beta-adrenergic binding sites was dependent on the formation of phosphatidylcholine by the enzyme that converts phosphatidyl-N-monomethylethanolamine from phosphatidylethanolamine. Both the synthesis of phosphatidylcholine and the unmasking of cryptic receptors were time and temperature dependent and did not occur in the presence of the methyl transferase inhibitor, S-adenosyl-L-homocysteine.", "contents": "Phospholipid methylation unmasks cryptic beta-adrenergic receptors in rat reticulocytes. The effect of phospholipid methylation on the number of beta-adrenergic receptor binding sites was examined in rat reticulocyte membranes. Stimulation of phosphatidylcholine synthesis by the introduction of the methyl donor S-adenosyl-L-methionine into reticulocyte ghosts increased the number of beta-adrenergic receptor sites. The appearance of beta-adrenergic binding sites was dependent on the formation of phosphatidylcholine by the enzyme that converts phosphatidyl-N-monomethylethanolamine from phosphatidylethanolamine. Both the synthesis of phosphatidylcholine and the unmasking of cryptic receptors were time and temperature dependent and did not occur in the presence of the methyl transferase inhibitor, S-adenosyl-L-homocysteine."}
{"id": "PMID:221978", "title": "Effect of fluorine substitution on the agonist specificity of norepinephrine.", "content": "Substitution of fluorine for hydrogen in position 2, 5, or 6 of the aromatic ring of norepinephrine markedly alters the alpha- and beta-adrenergic agonist properties of norephinephrine. The 6-fluoro isomer is an beta-adrenergic agonist with virtually no beta agonist activity, while the 2-fluoro isomer is a beta-adrenergic agonist with little alpha activity. The 5-fluoro isomer is equipotent with norepinephrine as an alpha agonist and significantly more potent as a beta agonist. The possible physiochemical basis for these differences is discussed.", "contents": "Effect of fluorine substitution on the agonist specificity of norepinephrine. Substitution of fluorine for hydrogen in position 2, 5, or 6 of the aromatic ring of norepinephrine markedly alters the alpha- and beta-adrenergic agonist properties of norephinephrine. The 6-fluoro isomer is an beta-adrenergic agonist with virtually no beta agonist activity, while the 2-fluoro isomer is a beta-adrenergic agonist with little alpha activity. The 5-fluoro isomer is equipotent with norepinephrine as an alpha agonist and significantly more potent as a beta agonist. The possible physiochemical basis for these differences is discussed."}
{"id": "PMID:221979", "title": "Norepinephrine inhibits calcium-dependent potentials in rat sympathetic neurons.", "content": "Norepinephrine reversibly antagonizes three calcium-dependent potentials recorded from rat postganglionic neurons. Norepinephrine inhibits the development of a shoulder on the aciton potential, the magnitude of the hyperpolarizing afterpotential, and the rate of rise and amplitude of the calcium spike. The action of norepinephrine is antagonized by the alpha-adrenergic antagonist phentolamine, but not by MJ 1999, a beta-adrenergic antagonist. These results suggest that activation of an alpha-adrenergic receptor may antagonize a voltage-sensitive calcium current.", "contents": "Norepinephrine inhibits calcium-dependent potentials in rat sympathetic neurons. Norepinephrine reversibly antagonizes three calcium-dependent potentials recorded from rat postganglionic neurons. Norepinephrine inhibits the development of a shoulder on the aciton potential, the magnitude of the hyperpolarizing afterpotential, and the rate of rise and amplitude of the calcium spike. The action of norepinephrine is antagonized by the alpha-adrenergic antagonist phentolamine, but not by MJ 1999, a beta-adrenergic antagonist. These results suggest that activation of an alpha-adrenergic receptor may antagonize a voltage-sensitive calcium current."}
{"id": "PMID:221980", "title": "Angiotensin convertase activities in human alveolar macrophages: effects of cigarette smoking and sarcoidosis.", "content": "Angiotensin I convertase activity has been found in human alveolar macrophages from normal volunteers and patients with pulmonary sarcoidosis. This activity is higher in the alveolar macrophages from smokers than from nonsmokers, and is even more elevated in sarcoid patients. The activity can be detected with both angiotensin I and bradykinin analogs and appears to require protein synthesis, but the enzyme is not secreted by alveolar macrophages in culture.", "contents": "Angiotensin convertase activities in human alveolar macrophages: effects of cigarette smoking and sarcoidosis. Angiotensin I convertase activity has been found in human alveolar macrophages from normal volunteers and patients with pulmonary sarcoidosis. This activity is higher in the alveolar macrophages from smokers than from nonsmokers, and is even more elevated in sarcoid patients. The activity can be detected with both angiotensin I and bradykinin analogs and appears to require protein synthesis, but the enzyme is not secreted by alveolar macrophages in culture."}
{"id": "PMID:221982", "title": "Nonimpulse-mediated synaptic transmission during the generation of a cyclic motor program.", "content": "A small neuronal network in the lobster stomatogastric ganglion, composed of impulse-producing motor neurons, gives rise to cyclic patterned outputs. This network continues to generate its cyclic motor program if impulse production within the ganglion is blocked. Continuously graded, nonimpulse-mediated, chemical synaptic transmission is suffucient to coordinate neuronal activity in a functioning pattern generator.", "contents": "Nonimpulse-mediated synaptic transmission during the generation of a cyclic motor program. A small neuronal network in the lobster stomatogastric ganglion, composed of impulse-producing motor neurons, gives rise to cyclic patterned outputs. This network continues to generate its cyclic motor program if impulse production within the ganglion is blocked. Continuously graded, nonimpulse-mediated, chemical synaptic transmission is suffucient to coordinate neuronal activity in a functioning pattern generator."}
{"id": "PMID:221983", "title": "Pituitary hormones in brain: where, how, and why?", "content": "Peptide and protein hormones usually considered as being of pituitary origin have been detected within the central nervous system by means of radioimmunoassay, bioassay, and immunocytochemical techniques. Intracerebral administration of some of these hormones or fragments thereof elicit behavioral responses, suggesting that they may have a physiological role similar to that described for other peptidergic neurotransmitter or neuromodulator substances. Evidence available for some of these hormones indicates that they are synthesized within the central nervous system and that their regulation may differ from that of their pituitary counterparts.", "contents": "Pituitary hormones in brain: where, how, and why? Peptide and protein hormones usually considered as being of pituitary origin have been detected within the central nervous system by means of radioimmunoassay, bioassay, and immunocytochemical techniques. Intracerebral administration of some of these hormones or fragments thereof elicit behavioral responses, suggesting that they may have a physiological role similar to that described for other peptidergic neurotransmitter or neuromodulator substances. Evidence available for some of these hormones indicates that they are synthesized within the central nervous system and that their regulation may differ from that of their pituitary counterparts."}
{"id": "PMID:221984", "title": "6-Hydroxydopamine potentiates acute herpes simplex virus infection of the superior cervical ganglion in mice.", "content": "Treatment of mice with 6-hydroxydopamine increased herpes simplex virus replication in the superior cervical ganglion while it decreased the subsequent prevalence of latent infection. Preganglionic neurectomy failed to block this effect. These observations suggest that intrinsic neural events modify the outcome of viral infections of the nervous system.", "contents": "6-Hydroxydopamine potentiates acute herpes simplex virus infection of the superior cervical ganglion in mice. Treatment of mice with 6-hydroxydopamine increased herpes simplex virus replication in the superior cervical ganglion while it decreased the subsequent prevalence of latent infection. Preganglionic neurectomy failed to block this effect. These observations suggest that intrinsic neural events modify the outcome of viral infections of the nervous system."}
{"id": "PMID:221988", "title": "Synchronous primary mucinous adenocarcinomas in the descending colon and perianal glands.", "content": "The descending colon is a relatively rare site for mucinous adenocarcinoma. Anal ductal malignancy and multiple primary coloperianal mucinous adenocarcinomas are also rare. We have described the unusual finding of multiple primary synchronous mucinous adenocarcinomas in the descending colon and perianal glands. There was no evidence of any metastasis from the Dukes B lesion in the descending colon.", "contents": "Synchronous primary mucinous adenocarcinomas in the descending colon and perianal glands. The descending colon is a relatively rare site for mucinous adenocarcinoma. Anal ductal malignancy and multiple primary coloperianal mucinous adenocarcinomas are also rare. We have described the unusual finding of multiple primary synchronous mucinous adenocarcinomas in the descending colon and perianal glands. There was no evidence of any metastasis from the Dukes B lesion in the descending colon."}
{"id": "PMID:221989", "title": "Cytomegalovirus infections.", "content": "Cytomegalovirus infections are common throughout the world. Certain populations, including pregnant women and their fetuses, immunosuppressed patients, and recipients of large amounts of transfused blood, are at increased risk. Although the majority of infections in all groups of patients are clinically inapparent, variable symptoms, including fever, rash, pneumonitis, and hepatitis, can occur. The infected host develops antibodies against CMF, but frequently, despite this appropriate immune response, infection becomes chronic with prolonged excretion of virus. In some instances, a latent infection, with disappearance of virus, develops and under a variety of circumstances, including immunosuppression, infection can later be reactivated with reappearance of viral excretion. The human consequences of latent infection with CMV are not yet fully appreciated, and future research on this virus with multifaceted potential will need to focus on this issue.", "contents": "Cytomegalovirus infections. Cytomegalovirus infections are common throughout the world. Certain populations, including pregnant women and their fetuses, immunosuppressed patients, and recipients of large amounts of transfused blood, are at increased risk. Although the majority of infections in all groups of patients are clinically inapparent, variable symptoms, including fever, rash, pneumonitis, and hepatitis, can occur. The infected host develops antibodies against CMF, but frequently, despite this appropriate immune response, infection becomes chronic with prolonged excretion of virus. In some instances, a latent infection, with disappearance of virus, develops and under a variety of circumstances, including immunosuppression, infection can later be reactivated with reappearance of viral excretion. The human consequences of latent infection with CMV are not yet fully appreciated, and future research on this virus with multifaceted potential will need to focus on this issue."}
{"id": "PMID:221996", "title": "Surgical importance of oblique projection in arteriography for carcinoma of the pancreas.", "content": "Oblique projections in celiac and superior mesenteric angiography have been of value in patients with carcinoma arising in various parts of the pancreas. Oblique views allow better perception of the slight and uncertain changes in the pancreatic vessels, which are not discernible on anteroposterior projections because of overlapping with the extrapancreatic vessels and the spine. Anteroposterior and oblique views of both celiac and superior mesenteric arteries are the first, and, therefore, the most essential, step in angiography of lesions of the pancreas.", "contents": "Surgical importance of oblique projection in arteriography for carcinoma of the pancreas. Oblique projections in celiac and superior mesenteric angiography have been of value in patients with carcinoma arising in various parts of the pancreas. Oblique views allow better perception of the slight and uncertain changes in the pancreatic vessels, which are not discernible on anteroposterior projections because of overlapping with the extrapancreatic vessels and the spine. Anteroposterior and oblique views of both celiac and superior mesenteric arteries are the first, and, therefore, the most essential, step in angiography of lesions of the pancreas."}
{"id": "PMID:221997", "title": "Evidence of reflexive beta adrenergic motor stimulation in the canine stomach and small intestine.", "content": "Studies in our laboratory have confirmed the previous observations that adequate electrical stimulation of either the left or right central vagus nerves in the dog after bilateral vagectomy produces relaxation of the stomach and small intestine. On the other hand, central vagal stimuli delivered to dogs that were either chronically reserpinized or were premedicated with the alpha adrenolytic phenoxybenzamine resulted in increased segmenting activity of these two organs. These excitatory responses were abolished by bilateral section of the sympathetic chains and could be reproduced by electrically stimulating the chains. The excitatory effects of either central vagal stimulation, peripheral sympathetic stimulation or intravenous isoproterenol administration could be abolished by dichloroisoproterenol. It was also determined that isoproterenol produced a tonic contraction of the separated muscularis mucosa which was distinguishable from a relaxation of the muscularis externa. It is suggested that a sympathetic pathway exists which is excitatory to the stomach and small intestine and that these excitatory effects are mediated by beta adrenergic neurotransmitters. The results further suggests that the beta excitatory reflex response is mediated by the muscularis mucosa as the target effector system.", "contents": "Evidence of reflexive beta adrenergic motor stimulation in the canine stomach and small intestine. Studies in our laboratory have confirmed the previous observations that adequate electrical stimulation of either the left or right central vagus nerves in the dog after bilateral vagectomy produces relaxation of the stomach and small intestine. On the other hand, central vagal stimuli delivered to dogs that were either chronically reserpinized or were premedicated with the alpha adrenolytic phenoxybenzamine resulted in increased segmenting activity of these two organs. These excitatory responses were abolished by bilateral section of the sympathetic chains and could be reproduced by electrically stimulating the chains. The excitatory effects of either central vagal stimulation, peripheral sympathetic stimulation or intravenous isoproterenol administration could be abolished by dichloroisoproterenol. It was also determined that isoproterenol produced a tonic contraction of the separated muscularis mucosa which was distinguishable from a relaxation of the muscularis externa. It is suggested that a sympathetic pathway exists which is excitatory to the stomach and small intestine and that these excitatory effects are mediated by beta adrenergic neurotransmitters. The results further suggests that the beta excitatory reflex response is mediated by the muscularis mucosa as the target effector system."}
{"id": "PMID:221993", "title": "Sensitivity and specificity of diagnostic tests for genital infection with herpesvirus hominis.", "content": "Three smear techniques for diagnosis of Herpesvirus hominis infection were evaluated by study of 168 unselected patients with genital lesions attending a venereal disease clinic. A tissue culture and results of three smear techniques were obtained for each patient in random order. H. hominis was recovered from 101 patients (60%). All three smear tests (immunofluorescence, Papanicolaou, and crystal violet) were highly specific, but the sensitivity of each was smaller than or equal to 40% among patients who had ulcerative lesions. Because H. hominis is a common cause of genital lesions and the clinical manifestations of disease are highly variable, future research must identify accurate diagnostic aids that are suitable for clinic use.", "contents": "Sensitivity and specificity of diagnostic tests for genital infection with herpesvirus hominis. Three smear techniques for diagnosis of Herpesvirus hominis infection were evaluated by study of 168 unselected patients with genital lesions attending a venereal disease clinic. A tissue culture and results of three smear techniques were obtained for each patient in random order. H. hominis was recovered from 101 patients (60%). All three smear tests (immunofluorescence, Papanicolaou, and crystal violet) were highly specific, but the sensitivity of each was smaller than or equal to 40% among patients who had ulcerative lesions. Because H. hominis is a common cause of genital lesions and the clinical manifestations of disease are highly variable, future research must identify accurate diagnostic aids that are suitable for clinic use."}
{"id": "PMID:221992", "title": "Strategic planning system for control of venereal disease: record keeping in a clinic for treatment of sexually transmitted diseases.", "content": "A manual data processing system and a computer-based system that was integrated into the operations of a clinic for treatment of sexually transmitted diseases were developed. The automated system can generate routine management reports and cross-tabulate data for special studies. It is flexible and adaptable to other localities but is not a panacea for clinical problems.", "contents": "Strategic planning system for control of venereal disease: record keeping in a clinic for treatment of sexually transmitted diseases. A manual data processing system and a computer-based system that was integrated into the operations of a clinic for treatment of sexually transmitted diseases were developed. The automated system can generate routine management reports and cross-tabulate data for special studies. It is flexible and adaptable to other localities but is not a panacea for clinical problems."}
{"id": "PMID:221998", "title": "Transnasal excision of a neurohypophyseal tumor.", "content": "Neurohypophyseal tumors are rare. A case of a glioma of the neurohypophysis is presented. The tumor closely resembled pituicytomas or infundibulomas. Management of these lesions poses special problems as their natural history is unclear. This tumor was excised via the transnasal, transphenoidal route and there has been no recurrence during the subsequent thirty months. The transnasal approach for posterior lobe tumors appears to be acceptable for those confined to the sella turcica or displaying minimal suprasellar extension. The literature is reviewed.", "contents": "Transnasal excision of a neurohypophyseal tumor. Neurohypophyseal tumors are rare. A case of a glioma of the neurohypophysis is presented. The tumor closely resembled pituicytomas or infundibulomas. Management of these lesions poses special problems as their natural history is unclear. This tumor was excised via the transnasal, transphenoidal route and there has been no recurrence during the subsequent thirty months. The transnasal approach for posterior lobe tumors appears to be acceptable for those confined to the sella turcica or displaying minimal suprasellar extension. The literature is reviewed."}
{"id": "PMID:221999", "title": "Computerized tomography of coagulation necrosis of the brain and brain tumors.", "content": "Diffuse contrast enhancement was observed on computerized tomography (CT) of coagulation necrosis of the brain and brain tumor. CT scans of delayed radiation necrosis of the brain seen in two patients showed a low absorption that was diffusely enhanced after an intravenous injection of contrast medium. Areas of central coagulation necrosis of anaplastic gliomas in two patients exhibited a marked contrast enhancement which was characterized by a prolonged increase in attenuation and a delayed elimination of the contrast medium.", "contents": "Computerized tomography of coagulation necrosis of the brain and brain tumors. Diffuse contrast enhancement was observed on computerized tomography (CT) of coagulation necrosis of the brain and brain tumor. CT scans of delayed radiation necrosis of the brain seen in two patients showed a low absorption that was diffusely enhanced after an intravenous injection of contrast medium. Areas of central coagulation necrosis of anaplastic gliomas in two patients exhibited a marked contrast enhancement which was characterized by a prolonged increase in attenuation and a delayed elimination of the contrast medium."}
{"id": "PMID:222000", "title": "Continuous monitoring and control of plasma glucose during operation for removal of insulinomas.", "content": "A glucose-controlled insulin and glucose infusion system (Biostator system, Miles Laboratories Inc., Elkhart, Ind.) was used during operation for removal of four suspected insulinomas. In two patients the Biostator system continuously monitored plasma glucose levels and, through a computer-controlled feedback mechanism, automatically infused insulin or glucose as needed. In this way plasma glucose could be kept at approximately 110 mg/dl throughout the procedure. In one patient a rise in insulin infusion rate and a fall in glucose infusion rate followed removal of the tumor. In the other, absence of these findings was consistent with the clinical suspicion that the source of hypoglycemia had not been removed. In two other patients the Biostator system continuously monitored the patient's plasma glucose, without feedback-controlled administration of insulin or glucose. This demonstrated that, in these patients, tumor manipulation and removal did not lead to severe hypoglycemia, and thus eliminated any need to prophylactically infuse large amounts of glucose. Successful tumor removal was followed by a rise in blood glucose levels in both of these individuals. The glucose-controlled insulin and glucose infusion system appears to be a useful instrument for intraoperative management of patients with suspected insulinomas.", "contents": "Continuous monitoring and control of plasma glucose during operation for removal of insulinomas. A glucose-controlled insulin and glucose infusion system (Biostator system, Miles Laboratories Inc., Elkhart, Ind.) was used during operation for removal of four suspected insulinomas. In two patients the Biostator system continuously monitored plasma glucose levels and, through a computer-controlled feedback mechanism, automatically infused insulin or glucose as needed. In this way plasma glucose could be kept at approximately 110 mg/dl throughout the procedure. In one patient a rise in insulin infusion rate and a fall in glucose infusion rate followed removal of the tumor. In the other, absence of these findings was consistent with the clinical suspicion that the source of hypoglycemia had not been removed. In two other patients the Biostator system continuously monitored the patient's plasma glucose, without feedback-controlled administration of insulin or glucose. This demonstrated that, in these patients, tumor manipulation and removal did not lead to severe hypoglycemia, and thus eliminated any need to prophylactically infuse large amounts of glucose. Successful tumor removal was followed by a rise in blood glucose levels in both of these individuals. The glucose-controlled insulin and glucose infusion system appears to be a useful instrument for intraoperative management of patients with suspected insulinomas."}
{"id": "PMID:221994", "title": "Life-threatening pharyngitis caused by herpes simplex virus, type 2.", "content": "A 21-year-old man who had pharyngitis needed hospitalization for observation of airway patency and for parenteral fluid therapy. Infection with herpes simplex virus, type 2 (HSV-2), was diagnosed on the basis of the finding of significantly increased IgM indirect hemagglutination antibody titers. The pharyngitis appeared to have been contracted by heterosexual orogenital contact (cunnilingus). The results of this case study indicate that HSV-2 infection should be considered in the differential diagnosis in cases of severe pharyngitis in sexually active patients.", "contents": "Life-threatening pharyngitis caused by herpes simplex virus, type 2. A 21-year-old man who had pharyngitis needed hospitalization for observation of airway patency and for parenteral fluid therapy. Infection with herpes simplex virus, type 2 (HSV-2), was diagnosed on the basis of the finding of significantly increased IgM indirect hemagglutination antibody titers. The pharyngitis appeared to have been contracted by heterosexual orogenital contact (cunnilingus). The results of this case study indicate that HSV-2 infection should be considered in the differential diagnosis in cases of severe pharyngitis in sexually active patients."}
{"id": "PMID:222001", "title": "Caffeine, cyclic nucleotides, and breast disease.", "content": "Methylxanthine consumption is associated with the development of fibrocystic disease of the breast. Methylxanthine abstention is associated with resolution of signs and symptoms of fibrocystic disease. Abstinence from methylxanthine consumption decreased breast biopsies and the need for major breast surgery because of benign disease. Methylxanthine consumption is associated with elevated cyclic adenosine monophosphate (AMP) and cyclic guanosine monophosphate (GMP) values in fibrocystic dsiease over those obtained in normal breast tissue.", "contents": "Caffeine, cyclic nucleotides, and breast disease. Methylxanthine consumption is associated with the development of fibrocystic disease of the breast. Methylxanthine abstention is associated with resolution of signs and symptoms of fibrocystic disease. Abstinence from methylxanthine consumption decreased breast biopsies and the need for major breast surgery because of benign disease. Methylxanthine consumption is associated with elevated cyclic adenosine monophosphate (AMP) and cyclic guanosine monophosphate (GMP) values in fibrocystic dsiease over those obtained in normal breast tissue."}
{"id": "PMID:222006", "title": "The structure of a new sialic acid-containing decasaccharide from the urine of a patient with mucolipidosis.", "content": "A new sialic acid-containing oligosaccharide has been isolated from urine of a patient with a type of mucolipidosis newly recognized by Orii et al. (1972). This compound was found to be composed of galactose (2 moles), mannose (3 moles), N-acetylglucosamine (3 moles) and sialic acid (2 moles). On the basis of the results of sequential glycosidase digestion, of methylation analysis, and of the Smith degradation, the structure of this oligosaccharide was elucidated as follows: NeuAcalpha2-6Galbeta1-4GlcNAcbeta1-2Manalpha1-3[NeuAcalpha2-6Galbeta1-4GlcNAcbeta1-2Manalpha1-6]Manbeta1-4GlcNAc. The increased excretion of this oligosaccharide may be caused by the impaired metabolism of glycoproteins having N-glycosidic linkage.", "contents": "The structure of a new sialic acid-containing decasaccharide from the urine of a patient with mucolipidosis. A new sialic acid-containing oligosaccharide has been isolated from urine of a patient with a type of mucolipidosis newly recognized by Orii et al. (1972). This compound was found to be composed of galactose (2 moles), mannose (3 moles), N-acetylglucosamine (3 moles) and sialic acid (2 moles). On the basis of the results of sequential glycosidase digestion, of methylation analysis, and of the Smith degradation, the structure of this oligosaccharide was elucidated as follows: NeuAcalpha2-6Galbeta1-4GlcNAcbeta1-2Manalpha1-3[NeuAcalpha2-6Galbeta1-4GlcNAcbeta1-2Manalpha1-6]Manbeta1-4GlcNAc. The increased excretion of this oligosaccharide may be caused by the impaired metabolism of glycoproteins having N-glycosidic linkage."}
{"id": "PMID:222014", "title": "Isolation of urinary C-20 alpha- and C-20 beta-hydroxy-C21-steroid metabolites in cases of congenital adrenal hyperplasia, postpubertal virilizing syndrome and polycystic ovary syndrome.", "content": "The proportion of 20 alpha/20 beta-epimers of the urinary C21-steroid metabolites was estimated in normal volunteers and in patients with congenital adrenal hyperplasia (CAH), postpubertal virilizing syndrome (PVS) and polycystic ovary syndrome (POS). In the normal individuals 20 alpha- and 20 beta-epimers of 5 beta-pregnane-3 alpha, 17 alpha, 20-triol (pregnanetriol) and 5-pregnene-3 beta, 17 alpha, 20-triol (5-pregnenetriol) were measured. In the other case 20 alpha- and 20 beta-epimers of the characteristic, representative metabolites were also investigated. In 26 of 27 normal persons and in all the patients with normotensive CAH, PVS and POS the 20 beta-epimer comprised 0-10% of the total pregnanetriol. The 20 beta-epimer of 5-pregnenetriol was found in only one normal case (6% of the total). The percentage of 20 beta-epimers of 3 alpha, 17 alpha, 20-trihydroxy-5 beta-pregnan-11-one, 5 beta-pregnane-3 alpha, 11 beta, 17 alpha, 20-tetrol (in the normotensive CAH, PVS and POS) and 5 alpha- or 5 beta-pregnane-3 alpha, 17 alpha, 20, 21-tetrol (in the hypertensive CAH) varied from nil to 76%. The effect of functional groups and the stereochemistry of the molecule on the direction of C-20-keto group reduction is discussed; the existence of additional factors determining this reduction in certain pathological conditions is suggested.", "contents": "Isolation of urinary C-20 alpha- and C-20 beta-hydroxy-C21-steroid metabolites in cases of congenital adrenal hyperplasia, postpubertal virilizing syndrome and polycystic ovary syndrome. The proportion of 20 alpha/20 beta-epimers of the urinary C21-steroid metabolites was estimated in normal volunteers and in patients with congenital adrenal hyperplasia (CAH), postpubertal virilizing syndrome (PVS) and polycystic ovary syndrome (POS). In the normal individuals 20 alpha- and 20 beta-epimers of 5 beta-pregnane-3 alpha, 17 alpha, 20-triol (pregnanetriol) and 5-pregnene-3 beta, 17 alpha, 20-triol (5-pregnenetriol) were measured. In the other case 20 alpha- and 20 beta-epimers of the characteristic, representative metabolites were also investigated. In 26 of 27 normal persons and in all the patients with normotensive CAH, PVS and POS the 20 beta-epimer comprised 0-10% of the total pregnanetriol. The 20 beta-epimer of 5-pregnenetriol was found in only one normal case (6% of the total). The percentage of 20 beta-epimers of 3 alpha, 17 alpha, 20-trihydroxy-5 beta-pregnan-11-one, 5 beta-pregnane-3 alpha, 11 beta, 17 alpha, 20-tetrol (in the normotensive CAH, PVS and POS) and 5 alpha- or 5 beta-pregnane-3 alpha, 17 alpha, 20, 21-tetrol (in the hypertensive CAH) varied from nil to 76%. The effect of functional groups and the stereochemistry of the molecule on the direction of C-20-keto group reduction is discussed; the existence of additional factors determining this reduction in certain pathological conditions is suggested."}
{"id": "PMID:222015", "title": "Concomitant T- and Tk-activation associated with acquired-B antigens.", "content": "Three patients with acquired-B antigens are reported whose red blood cells also manifested T- and Tk-activation. The results of tests using purified Arachis hypogaea and Bandeiraea simplicifolia (BS II) lectins, and red blood cells either T, Tk or both T and Tk-activated by bacterial enzymes in vitro, suggest that the acquired-B phenomenon, T-activation and Tk-activation result from the action of different bacterial enzymes.", "contents": "Concomitant T- and Tk-activation associated with acquired-B antigens. Three patients with acquired-B antigens are reported whose red blood cells also manifested T- and Tk-activation. The results of tests using purified Arachis hypogaea and Bandeiraea simplicifolia (BS II) lectins, and red blood cells either T, Tk or both T and Tk-activated by bacterial enzymes in vitro, suggest that the acquired-B phenomenon, T-activation and Tk-activation result from the action of different bacterial enzymes."}
{"id": "PMID:222019", "title": "Treatment of life-threatening infections in renal transplant recipients with high-dose intravenous human IgG.", "content": "This study demonstrates that large doses of human IgG can, if prepared by appropriate methods, be safely given intravenously. Antibody titers to CMV can be significantly elevated by administration of MIVIgG. While this is not a controlled trial, IgG therapy appears to be beneficial in renal transplant patients presenting with life-threatening infections.", "contents": "Treatment of life-threatening infections in renal transplant recipients with high-dose intravenous human IgG. This study demonstrates that large doses of human IgG can, if prepared by appropriate methods, be safely given intravenously. Antibody titers to CMV can be significantly elevated by administration of MIVIgG. While this is not a controlled trial, IgG therapy appears to be beneficial in renal transplant patients presenting with life-threatening infections."}
{"id": "PMID:222025", "title": "[Active transport of organic acids in the proximal tubules of the surviving rat kidney normally and under various influences. II. The effect of exogenous cyclic 3',5'-AMP and of substances that alter its intracellular concentration].", "content": "Exogenous cyclic 3',5'-AMP (cAMP) and substances known to increase the intracellular concentration of this nucleotide (isoproterenol, theophylline, noradrenaline, lactate) were shown to inhibit the transport of fluorescein (a weak organic acid) into the rat renal proximal tubules at 20 degrees C. Carbacholine decreasing intracellular cAMP concentration stimulated the transport. Propranolol, a beta-adrenergic blockator, diminished significantly the inhibitory effect of noradrenaline on the transport. Lactate and carbacholine when added simultaneously, neutralize their action. The inhibitory action of intracellular cAMP on the transport is supposed to be a result of the diminition of a pool of endogenous weak organic acids which may take part in the exchange of diffusion with the marker anion across basal plasma membrane.", "contents": "[Active transport of organic acids in the proximal tubules of the surviving rat kidney normally and under various influences. II. The effect of exogenous cyclic 3',5'-AMP and of substances that alter its intracellular concentration]. Exogenous cyclic 3',5'-AMP (cAMP) and substances known to increase the intracellular concentration of this nucleotide (isoproterenol, theophylline, noradrenaline, lactate) were shown to inhibit the transport of fluorescein (a weak organic acid) into the rat renal proximal tubules at 20 degrees C. Carbacholine decreasing intracellular cAMP concentration stimulated the transport. Propranolol, a beta-adrenergic blockator, diminished significantly the inhibitory effect of noradrenaline on the transport. Lactate and carbacholine when added simultaneously, neutralize their action. The inhibitory action of intracellular cAMP on the transport is supposed to be a result of the diminition of a pool of endogenous weak organic acids which may take part in the exchange of diffusion with the marker anion across basal plasma membrane."}
{"id": "PMID:222031", "title": "Carcinoma of colon after ureterocolic anastomosis: implantation on calyceal mucosa.", "content": "Two cases are reported of the development of mucoid adenocarcinoma of the colon in young patients, nineteen and thirty-four years after ureterocolic anastomosis for benign conditions. One patient showed implantation of the colonic neoplasm on the mucosa of an upper calyx in the obstructed kidney. Patients who have undergone ureterocolic anastomosis have a greatly increased risk of the development of large-bowel neoplasms. When suspected, radiologic examination of the colon using a water-soluble contrast material, together with rectosigmoidoscopy or colonoscopy, is essential. Because of the serious nature of this complication, it is suggested that the recent trend to return to the use of large bowel in urinary diversion may be hazardous, especially in the young patient with a benign disease.", "contents": "Carcinoma of colon after ureterocolic anastomosis: implantation on calyceal mucosa. Two cases are reported of the development of mucoid adenocarcinoma of the colon in young patients, nineteen and thirty-four years after ureterocolic anastomosis for benign conditions. One patient showed implantation of the colonic neoplasm on the mucosa of an upper calyx in the obstructed kidney. Patients who have undergone ureterocolic anastomosis have a greatly increased risk of the development of large-bowel neoplasms. When suspected, radiologic examination of the colon using a water-soluble contrast material, together with rectosigmoidoscopy or colonoscopy, is essential. Because of the serious nature of this complication, it is suggested that the recent trend to return to the use of large bowel in urinary diversion may be hazardous, especially in the young patient with a benign disease."}
{"id": "PMID:222032", "title": "Prostatic mucinous carcinoma.", "content": "Four criteria are proposed for establishing the pathologic diagnosis of prostatic mucinous carcinoma. Twenty-one reported cases of this rare tumor are reviewed, and a new case is presented. The clinical and pathologic features of 16 authentic features of 16 authentic cases are analyzed.", "contents": "Prostatic mucinous carcinoma. Four criteria are proposed for establishing the pathologic diagnosis of prostatic mucinous carcinoma. Twenty-one reported cases of this rare tumor are reviewed, and a new case is presented. The clinical and pathologic features of 16 authentic features of 16 authentic cases are analyzed."}
{"id": "PMID:222027", "title": "[Purification and properties of two forms of soluble 3',5'-AMP-dependent protein kinase from rabbit myocardium].", "content": "Two forms of 3' : 5'-AMP-dependent protein kinase were purified from the rabbit myocardium. The concentrations of 3' : 5'-AMP-necessary for maximum stimulation of form I and II were the same but the second form of the enzyme was activated by this concentration to a greater extent. The seeming Km by ATP for the both forms in the presence of 3' : 5'-AMP is found to be 8.3.10(-6)M. For enzyme form I the seeming Km by histone H1 was 0.43 mg/ml and for form II--0.67 mg/ml.", "contents": "[Purification and properties of two forms of soluble 3',5'-AMP-dependent protein kinase from rabbit myocardium]. Two forms of 3' : 5'-AMP-dependent protein kinase were purified from the rabbit myocardium. The concentrations of 3' : 5'-AMP-necessary for maximum stimulation of form I and II were the same but the second form of the enzyme was activated by this concentration to a greater extent. The seeming Km by ATP for the both forms in the presence of 3' : 5'-AMP is found to be 8.3.10(-6)M. For enzyme form I the seeming Km by histone H1 was 0.43 mg/ml and for form II--0.67 mg/ml."}
{"id": "PMID:222026", "title": "[Aminotransferase and dehydrogenase activity in human brain tumours].", "content": "Asparate and alanine aminotransferase activity is approximately the same in different lobes of cerebral hemispheres of people with an uninjured central nervous system. The maximal activity of lactate, malate and succinate dehydrogenase is in the temporal lobes and thalami, the minimal one is in the corpus callosum. The activity of aminotransferases in the brain tumour lowers: in the dedifferentiated tumour the asparate aminotransferase shows a 23-24% decrease; in the case of the meningeal sarcoma it is 2.5 times as low: the activity of alaine aminogransferase is almost 10 times as low. The activity of malate dehydrogenase decreases in the neuroectodermal tumours and sharply (almost twice) in multiform glioblastoma. In the dedifferentiated meningiomas the activity of all the dehydrogenases is increased.", "contents": "[Aminotransferase and dehydrogenase activity in human brain tumours]. Asparate and alanine aminotransferase activity is approximately the same in different lobes of cerebral hemispheres of people with an uninjured central nervous system. The maximal activity of lactate, malate and succinate dehydrogenase is in the temporal lobes and thalami, the minimal one is in the corpus callosum. The activity of aminotransferases in the brain tumour lowers: in the dedifferentiated tumour the asparate aminotransferase shows a 23-24% decrease; in the case of the meningeal sarcoma it is 2.5 times as low: the activity of alaine aminogransferase is almost 10 times as low. The activity of malate dehydrogenase decreases in the neuroectodermal tumours and sharply (almost twice) in multiform glioblastoma. In the dedifferentiated meningiomas the activity of all the dehydrogenases is increased."}
{"id": "PMID:222028", "title": "[Effect of potassium orotate and guanine on calcium uptake in small intestine of chickens with different amounts of vitamin D3].", "content": "Potassium orotate and guanine are established to accelerate the duodenum physiological response of chickens with experimental rachitis to administration of vitamin D3 in the in vivo experiments. They stumulate the uptake and transport of calcium, increase the content of calcium-binding protein and affect the activity of alkaline phosphatase. Guanine is a more effective stimulator as compared to orotate. A rise in the calcium uptake in the duodenum of the chicken which were given guanine started considerably earlier than the intensification of the calcium-binding protein synthesis in it. This suggests a possibility of the calcium uptake initiation by vitamin D3 through the mechanisims independent of the calcium-binding protein biosynthesis.", "contents": "[Effect of potassium orotate and guanine on calcium uptake in small intestine of chickens with different amounts of vitamin D3]. Potassium orotate and guanine are established to accelerate the duodenum physiological response of chickens with experimental rachitis to administration of vitamin D3 in the in vivo experiments. They stumulate the uptake and transport of calcium, increase the content of calcium-binding protein and affect the activity of alkaline phosphatase. Guanine is a more effective stimulator as compared to orotate. A rise in the calcium uptake in the duodenum of the chicken which were given guanine started considerably earlier than the intensification of the calcium-binding protein synthesis in it. This suggests a possibility of the calcium uptake initiation by vitamin D3 through the mechanisims independent of the calcium-binding protein biosynthesis."}
{"id": "PMID:222035", "title": "Ovine pulmonary cytomegalovirus.", "content": "Cytomegalic cells with intranuclear inclusions were identified in lung tissue from one of two weanling Western lambs with pneumonia and Mycoplasma ovipneumoniae infection. On the basis of light and electron microscopy, cytomegalovirus infection was diagnosed. Arrays of viral particles whose morphology was consistent with that of viruses of the herpes group were in the intranuclear inclusions of cytomegalic cells.", "contents": "Ovine pulmonary cytomegalovirus. Cytomegalic cells with intranuclear inclusions were identified in lung tissue from one of two weanling Western lambs with pneumonia and Mycoplasma ovipneumoniae infection. On the basis of light and electron microscopy, cytomegalovirus infection was diagnosed. Arrays of viral particles whose morphology was consistent with that of viruses of the herpes group were in the intranuclear inclusions of cytomegalic cells."}
{"id": "PMID:222036", "title": "Quantitative observations on experimental reo-like virus (rotavirus) infection in colostrum-deprived calves.", "content": "Ten calves were challenged with one of two strains of reo-like virus (rotavirus). Changes in the daily faecal and urinary outputs were monitored and packed cell volume, plasma sodium, potassium and urea levels were measured. Faeces were examined for the presence of rotavirus by direct electron microscopy and immunofluorescence in cultures of PK(15) cells. All calves excreted rotavirus in the faeces for several days. Two calves remained clinically normal throughout the experiment, but in the remaining calves, faeces became mucoid in consistency and yellow-white in colour. In only two calves did the daily faecal output exceed 500 g with a fall in the dry matter content to less than 10 per cent. Slightly elevated blood urea levels and hyperkalaemia were the only changes observed in blood chemistry and these quickly returned to normal. Virus antigen was observed in the epithelial cells by immunofluorescence in the proximal and middle small intestine of calves. Pathological lesions occurred predominantly in the proximal small intestine of nine calves examined.", "contents": "Quantitative observations on experimental reo-like virus (rotavirus) infection in colostrum-deprived calves. Ten calves were challenged with one of two strains of reo-like virus (rotavirus). Changes in the daily faecal and urinary outputs were monitored and packed cell volume, plasma sodium, potassium and urea levels were measured. Faeces were examined for the presence of rotavirus by direct electron microscopy and immunofluorescence in cultures of PK(15) cells. All calves excreted rotavirus in the faeces for several days. Two calves remained clinically normal throughout the experiment, but in the remaining calves, faeces became mucoid in consistency and yellow-white in colour. In only two calves did the daily faecal output exceed 500 g with a fall in the dry matter content to less than 10 per cent. Slightly elevated blood urea levels and hyperkalaemia were the only changes observed in blood chemistry and these quickly returned to normal. Virus antigen was observed in the epithelial cells by immunofluorescence in the proximal and middle small intestine of calves. Pathological lesions occurred predominantly in the proximal small intestine of nine calves examined."}
{"id": "PMID:222068", "title": "[Biochemical changes in the adrenals and their function in mechanical trauma].", "content": "Concentration of corticosterene, activities of succinate dehydrogenase and cytochrome oxidase, contents of ascorbic acid, reduced glutathione, free amino acids, RNA and DNA were studied in rat and rabbit adrenal glands within 10 min, 5, 10 and 24 hrs after crushing of the soft tissues of posterior extremities under conditions of unaltered and stimulated by ACTH functioning of adrenal glands. Stable increase in the biochemical parameters studied, caused by the ACTH effect, occurred in adrenal glands under this pathology.", "contents": "[Biochemical changes in the adrenals and their function in mechanical trauma]. Concentration of corticosterene, activities of succinate dehydrogenase and cytochrome oxidase, contents of ascorbic acid, reduced glutathione, free amino acids, RNA and DNA were studied in rat and rabbit adrenal glands within 10 min, 5, 10 and 24 hrs after crushing of the soft tissues of posterior extremities under conditions of unaltered and stimulated by ACTH functioning of adrenal glands. Stable increase in the biochemical parameters studied, caused by the ACTH effect, occurred in adrenal glands under this pathology."}
{"id": "PMID:222069", "title": "[Seasonal fluctuations in the kallikrein-kinin system indices].", "content": "State of kallikrein-kinine system was studied in 100 persons of young and mature age during various seasons of year. Season variations in content of kininogen, kallikreinogen as well as in BAEE-esterase activity of blood serum were observed in young persons. In mature persons the season variations of antitryptic and kininase activities were also observed in blood serum. The kinine system of young persons was apparently less subjected to season variations as compared with the persons of mature age.", "contents": "[Seasonal fluctuations in the kallikrein-kinin system indices]. State of kallikrein-kinine system was studied in 100 persons of young and mature age during various seasons of year. Season variations in content of kininogen, kallikreinogen as well as in BAEE-esterase activity of blood serum were observed in young persons. In mature persons the season variations of antitryptic and kininase activities were also observed in blood serum. The kinine system of young persons was apparently less subjected to season variations as compared with the persons of mature age."}
{"id": "PMID:222070", "title": "[Effect of hemodialysis on erythrocyte acetylcholinesterase and adenosine triphosphatase activity in chronic renal insufficiency].", "content": "Erythrocytes of patients with chronic kidney insufficiency exhibited high hexokinase activity as well as low activity of acetylcholinesterase and K+, Na+-dependent ATPase. The Km value of acetylcholinesterase for acetyl thiocholine was not altered in the reaction and the enzyme proved to be more resistant to heat denaturation. Therapy with permanent hemodialysis [8-10 hrs per day within some months] normalized K+, Na+-dependent ATPase activity and activated acetylcholinesterase. These effects may be considered as evidence for detoxication and normalization of metabolism. At the same time, high hexokinase activity and increased resistance of acetylcholinesterase to heat inactivation were maintained.", "contents": "[Effect of hemodialysis on erythrocyte acetylcholinesterase and adenosine triphosphatase activity in chronic renal insufficiency]. Erythrocytes of patients with chronic kidney insufficiency exhibited high hexokinase activity as well as low activity of acetylcholinesterase and K+, Na+-dependent ATPase. The Km value of acetylcholinesterase for acetyl thiocholine was not altered in the reaction and the enzyme proved to be more resistant to heat denaturation. Therapy with permanent hemodialysis [8-10 hrs per day within some months] normalized K+, Na+-dependent ATPase activity and activated acetylcholinesterase. These effects may be considered as evidence for detoxication and normalization of metabolism. At the same time, high hexokinase activity and increased resistance of acetylcholinesterase to heat inactivation were maintained."}
{"id": "PMID:222071", "title": "[Molecular mechanisms of hypothalamic hexapeptide regulation of the links in glycogen metabolism].", "content": "Alterations in content of glycogen as well as in activity of phosphorylase and phosphoprotein phosphatase were studied in various rat tissues after intravenous administration of a new hypothalamic hexapeptide Tyr-Gly-Leu-Pro-Gly-NH2. An increase in phosphoprotein phosphatase activity was observed in heart muscle, which correlated with transformation of phosphorylase A to the B form and with accumulation of glycogen. The opposite effect was found in liver tissue and sceletal muscle.", "contents": "[Molecular mechanisms of hypothalamic hexapeptide regulation of the links in glycogen metabolism]. Alterations in content of glycogen as well as in activity of phosphorylase and phosphoprotein phosphatase were studied in various rat tissues after intravenous administration of a new hypothalamic hexapeptide Tyr-Gly-Leu-Pro-Gly-NH2. An increase in phosphoprotein phosphatase activity was observed in heart muscle, which correlated with transformation of phosphorylase A to the B form and with accumulation of glycogen. The opposite effect was found in liver tissue and sceletal muscle."}
{"id": "PMID:222072", "title": "[Complexes of apo-B-containing lipoproteins and glycosaminoglycans with a density greater than 1.063 gML in the human aorta].", "content": "Interaction of lipoproteins of very low and low density with glycosaminoglycans was studied in vitro. Using analytical and preparative ultracentrifugation the complexes formed were shown to possess a density above 1.063 g/ml. Similar complexes were identified in extracts of human aorta. The formation of the complexes was stimulated in atherosclerotic impairments of aorta.", "contents": "[Complexes of apo-B-containing lipoproteins and glycosaminoglycans with a density greater than 1.063 gML in the human aorta]. Interaction of lipoproteins of very low and low density with glycosaminoglycans was studied in vitro. Using analytical and preparative ultracentrifugation the complexes formed were shown to possess a density above 1.063 g/ml. Similar complexes were identified in extracts of human aorta. The formation of the complexes was stimulated in atherosclerotic impairments of aorta."}
{"id": "PMID:222073", "title": "[Isolation of the plasma membranes of fat cells without using collagenase].", "content": "A method is described for isolation of plasmatic membranes of rat fatty cells immediately from fatty tissue without the treatment with collagenase. Homogenization of fatty tissue was carried out in large volumes of buffered sucrose and EDTA at room temperature followed by sucrose density gradient centrifugation. The preparations obtained exhibited high specific activity of the marker enzyme of plasmatic membranes [5'-nucleotidase and K+, Na+-ATPase], as well as high ability for specific binding of insulin.", "contents": "[Isolation of the plasma membranes of fat cells without using collagenase]. A method is described for isolation of plasmatic membranes of rat fatty cells immediately from fatty tissue without the treatment with collagenase. Homogenization of fatty tissue was carried out in large volumes of buffered sucrose and EDTA at room temperature followed by sucrose density gradient centrifugation. The preparations obtained exhibited high specific activity of the marker enzyme of plasmatic membranes [5'-nucleotidase and K+, Na+-ATPase], as well as high ability for specific binding of insulin."}
{"id": "PMID:222076", "title": "Effect of prostaglandins on hepatic cyclic nucleotide concentration, carbohydrate and lipid metabolism.", "content": "The effects of exogenous prostaglandin E(1) (PGE(1)) or prostaglandin E(2) (PGE(2)) were studied in the isolated perfused rat liver and in the intact canine liver in order to determine the possible physiological role of prostaglandins on hepatic carbohydrate and lipid metabolism. The data indicate that PGE(1) and PGE(2) did not stimulate cyclic AMP (cAMP) and cyclic GMP (cGMP) concentrations in intact dog liver and PGE(1) failed to stimulate cAMP or cGMP in fed or fasted perfused rat liver. PGE(1) did not promote hyperglycemia, glycogenolysis, lipolysis, or prevent epinephrine-induced hyperglycemia in the isolated perfused rat liver. Other known glycogenolytic agents including glucagon and epinephrine increased cAMP and glycogenolysis in the same perfusion system. This study does not support a physiologic role for PGE(1) on hepatic glycogenolysis or lipolysis. If PGE(1) subsequently is found to influence other metabolic parameters such as lipogenesis, gluconeogenesis, ureogenesis or amino acid transport in isolated perfused liver, such alterations would probably occur independent of changes in cyclic nucleotide activity.", "contents": "Effect of prostaglandins on hepatic cyclic nucleotide concentration, carbohydrate and lipid metabolism. The effects of exogenous prostaglandin E(1) (PGE(1)) or prostaglandin E(2) (PGE(2)) were studied in the isolated perfused rat liver and in the intact canine liver in order to determine the possible physiological role of prostaglandins on hepatic carbohydrate and lipid metabolism. The data indicate that PGE(1) and PGE(2) did not stimulate cyclic AMP (cAMP) and cyclic GMP (cGMP) concentrations in intact dog liver and PGE(1) failed to stimulate cAMP or cGMP in fed or fasted perfused rat liver. PGE(1) did not promote hyperglycemia, glycogenolysis, lipolysis, or prevent epinephrine-induced hyperglycemia in the isolated perfused rat liver. Other known glycogenolytic agents including glucagon and epinephrine increased cAMP and glycogenolysis in the same perfusion system. This study does not support a physiologic role for PGE(1) on hepatic glycogenolysis or lipolysis. If PGE(1) subsequently is found to influence other metabolic parameters such as lipogenesis, gluconeogenesis, ureogenesis or amino acid transport in isolated perfused liver, such alterations would probably occur independent of changes in cyclic nucleotide activity."}
{"id": "PMID:222078", "title": "The Berkson bias in action.", "content": "Thirty years ago Berkson recognized that differences in selection rates of different diseases for admission to the hospital will systematically change the frequency with which those diseases co-exist in hospitalized patients from the frequency rate in the general population. Mainland subsequently demonstrated that postmortem studies systematically show a lower co-morbidity rate for any two individually lethal diseases than would be expected from the individual prevalence of these diseases. In studying the concurrence of bacterial endocarditis and cirrhosis, we examined the relationship of these diseases at autopsy where, according to this concept, we would expect a negative association. We found the frequency of bacterial endocarditis to be three times greater in cirrhotic than in non-cirrhotic patients, a statistically significant difference that was even more convincing, since a negative correlation was anticipated. In accord with the Berkson-Mainland hypothesis, however, no such association was seen between bacterial endocarditis and either emphysema or myocardial infarction, two other chronic diseases of different lethality. Similarly, glioblastoma multiforme, a brain tumor with a high mortality rate, showed a negative correlation with cirrhosis, emphysema, and myocardial infarction. A corollary of this bias-that the mean age at death should be lower in patients dying with two lethal diseases than in patients dying of either disease alone-was supported by our study. This investigation provides evidence to validate the Berkson-Mainland hypothesis, and suggests that rather than being always an adverse bias, it may be used beneficially to document the validity of the increased co-existence of diseases at autopsy.", "contents": "The Berkson bias in action. Thirty years ago Berkson recognized that differences in selection rates of different diseases for admission to the hospital will systematically change the frequency with which those diseases co-exist in hospitalized patients from the frequency rate in the general population. Mainland subsequently demonstrated that postmortem studies systematically show a lower co-morbidity rate for any two individually lethal diseases than would be expected from the individual prevalence of these diseases. In studying the concurrence of bacterial endocarditis and cirrhosis, we examined the relationship of these diseases at autopsy where, according to this concept, we would expect a negative association. We found the frequency of bacterial endocarditis to be three times greater in cirrhotic than in non-cirrhotic patients, a statistically significant difference that was even more convincing, since a negative correlation was anticipated. In accord with the Berkson-Mainland hypothesis, however, no such association was seen between bacterial endocarditis and either emphysema or myocardial infarction, two other chronic diseases of different lethality. Similarly, glioblastoma multiforme, a brain tumor with a high mortality rate, showed a negative correlation with cirrhosis, emphysema, and myocardial infarction. A corollary of this bias-that the mean age at death should be lower in patients dying with two lethal diseases than in patients dying of either disease alone-was supported by our study. This investigation provides evidence to validate the Berkson-Mainland hypothesis, and suggests that rather than being always an adverse bias, it may be used beneficially to document the validity of the increased co-existence of diseases at autopsy."}
{"id": "PMID:222077", "title": "Hepatic heme metabolism and its control.", "content": "This review summarizes heme metabolism and focuses especially upon the control of hepatic heme biosynthesis. Activity of \u03b4-aminolevulinic acid synthetase, the first enzyme of heme biosynthesis, is of primary importance in controlling the overall activity of this biosynthetic pathway. \u0394-aminolevulinic acid synthetase is subject to inhibition and repression by heme, and numerous basic and clinical studies support the concept that there exists within hepatocytes a \"regulatory\" heme pool which controls activity of \u03b4-aminolevulinic acid synthetase. In addition, activity of this enzyme is repressed by feeding, especially by ingestion of carbohydrates (the so-called \"glucose effect\"). Studies pertaining to the mechanisms underlying this effect are also reviewed. The \"glucose effect\" appears to be mediated by glucose or perhaps by glucose-6-phosphate or uridine diphosphate glucose, rather than by metabolites further removed from glucose itself. Unlike the situation in E. coli, the \"glucose effect\" in liver of higher organisms is not mediated by alterations in intracellular concentrations of cyclic AMP. Effects of heavy metals, especially iron, on hepatic heme metabolism are also considered. Iron has been found to inhibit formation and utilization of uroporphyrinogen III and to lead to decreased concentrations of microsomal heme and cytochrome P-450. Administration of large amounts of iron is also associated with an increase in activity of heme oxygenase, a property shared by several other metal ions, most notably cobalt. This effect of iron or cobalt administration is similar to the effect of heme administration in increasing heme oxygenase activity; however, we believe it is unlikely that iron, rather than heme itself, is a physiologic regulator of hepatic heme metabolism, although this hypothesis has lately been proposed.", "contents": "Hepatic heme metabolism and its control. This review summarizes heme metabolism and focuses especially upon the control of hepatic heme biosynthesis. Activity of \u03b4-aminolevulinic acid synthetase, the first enzyme of heme biosynthesis, is of primary importance in controlling the overall activity of this biosynthetic pathway. \u0394-aminolevulinic acid synthetase is subject to inhibition and repression by heme, and numerous basic and clinical studies support the concept that there exists within hepatocytes a \"regulatory\" heme pool which controls activity of \u03b4-aminolevulinic acid synthetase. In addition, activity of this enzyme is repressed by feeding, especially by ingestion of carbohydrates (the so-called \"glucose effect\"). Studies pertaining to the mechanisms underlying this effect are also reviewed. The \"glucose effect\" appears to be mediated by glucose or perhaps by glucose-6-phosphate or uridine diphosphate glucose, rather than by metabolites further removed from glucose itself. Unlike the situation in E. coli, the \"glucose effect\" in liver of higher organisms is not mediated by alterations in intracellular concentrations of cyclic AMP. Effects of heavy metals, especially iron, on hepatic heme metabolism are also considered. Iron has been found to inhibit formation and utilization of uroporphyrinogen III and to lead to decreased concentrations of microsomal heme and cytochrome P-450. Administration of large amounts of iron is also associated with an increase in activity of heme oxygenase, a property shared by several other metal ions, most notably cobalt. This effect of iron or cobalt administration is similar to the effect of heme administration in increasing heme oxygenase activity; however, we believe it is unlikely that iron, rather than heme itself, is a physiologic regulator of hepatic heme metabolism, although this hypothesis has lately been proposed."}
{"id": "PMID:222079", "title": "Effects of hormones on changes in cytochrome P-450, prolyl hydroxylase, and glycerol phosphate acyltransferase in primary monolayer cultures of parenchymal cells from adult rat liver.", "content": "Previous studies have shown that isolation and primary culture of rat hepatocytes in a standard, chemically defined medium is associated with selective changes in microsomal function. These changes were found to be selectively sensitive to addition of hormones to the culture medium. The concentration of cytochrome P-450 declined dramatically during the first 24 hours of incubation. However, cytochrome P(1)-450, a form of the hemoprotein induced by polycyclic aromatic hydrocarbons, was resistant to this change. Cytochrome P(1)-450 levels selectively rose during the first ten hours in culture and, thereafter, declined at a less rapid rate than did the cytochrome P-450 in normal hepatocytes or in cells prepared from phenobarbital pretreated animals. Addition of dexamethasone to the medium at the time of cell plating partially prevented the fall of cytochrome P-450 and of (14)C-heme in microsomes prepared from hepatocytes derived from rats given 5(14)[C]-\u03b4-aminolevulinic acid. This suggests that the steroid decreases degradation of the hemoprotein. As compared to the loss of cytochrome P-450 in cultures of normal hepatocytes, the hemoprotein fell to lower levels in hepatocytes prepared from regenerated liver four days after partial hepatectomy. This result may be related to the accelerated formation of the monolayer in the cultures of regenerated hepatocytes. Both sn-glycerol-3-phosphate acyltransferase activity and glycerol kinase activity declined in the first 24 hours of culture. The fall in the latter enzyme was partially prevented by addition of estradiol. Collagen prolyl hydroxylase, a newly discovered microsomal constituent of the hepatocyte, rose slightly during the first 24 hours in culture. This change was augmented threefold by addition of insulin to the medium. We conclude that the present hepatocyte culture system with its attendant changes in functional phenotype may be useful in better defining the role of hormones in modulating metabolic processes in the liver.", "contents": "Effects of hormones on changes in cytochrome P-450, prolyl hydroxylase, and glycerol phosphate acyltransferase in primary monolayer cultures of parenchymal cells from adult rat liver. Previous studies have shown that isolation and primary culture of rat hepatocytes in a standard, chemically defined medium is associated with selective changes in microsomal function. These changes were found to be selectively sensitive to addition of hormones to the culture medium. The concentration of cytochrome P-450 declined dramatically during the first 24 hours of incubation. However, cytochrome P(1)-450, a form of the hemoprotein induced by polycyclic aromatic hydrocarbons, was resistant to this change. Cytochrome P(1)-450 levels selectively rose during the first ten hours in culture and, thereafter, declined at a less rapid rate than did the cytochrome P-450 in normal hepatocytes or in cells prepared from phenobarbital pretreated animals. Addition of dexamethasone to the medium at the time of cell plating partially prevented the fall of cytochrome P-450 and of (14)C-heme in microsomes prepared from hepatocytes derived from rats given 5(14)[C]-\u03b4-aminolevulinic acid. This suggests that the steroid decreases degradation of the hemoprotein. As compared to the loss of cytochrome P-450 in cultures of normal hepatocytes, the hemoprotein fell to lower levels in hepatocytes prepared from regenerated liver four days after partial hepatectomy. This result may be related to the accelerated formation of the monolayer in the cultures of regenerated hepatocytes. Both sn-glycerol-3-phosphate acyltransferase activity and glycerol kinase activity declined in the first 24 hours of culture. The fall in the latter enzyme was partially prevented by addition of estradiol. Collagen prolyl hydroxylase, a newly discovered microsomal constituent of the hepatocyte, rose slightly during the first 24 hours in culture. This change was augmented threefold by addition of insulin to the medium. We conclude that the present hepatocyte culture system with its attendant changes in functional phenotype may be useful in better defining the role of hormones in modulating metabolic processes in the liver."}
{"id": "PMID:222080", "title": "Ectopic ACTH syndrome due to pheochromocytoma: case report and review of the literature.", "content": "A 51-year-old female was diagnosed preoperatively to have a pheochromocytoma producing ACTH. This diagnosis was based upon her paroxysmal hypertension, hyperpigmentation, and hypokalemia. Elevated levels of serum and urine corticosteroids, plasma ACTH, urinary VMA, and catecholamines fell after a right adrenal pheochromocytoma was removed. Subsequently this tumor was found to have a high content of ACTH. Review of the literature indicates a mortality rate of 57% for this syndrome. Proper preoperative recognition and management can result in total cure.", "contents": "Ectopic ACTH syndrome due to pheochromocytoma: case report and review of the literature. A 51-year-old female was diagnosed preoperatively to have a pheochromocytoma producing ACTH. This diagnosis was based upon her paroxysmal hypertension, hyperpigmentation, and hypokalemia. Elevated levels of serum and urine corticosteroids, plasma ACTH, urinary VMA, and catecholamines fell after a right adrenal pheochromocytoma was removed. Subsequently this tumor was found to have a high content of ACTH. Review of the literature indicates a mortality rate of 57% for this syndrome. Proper preoperative recognition and management can result in total cure."}
{"id": "PMID:222082", "title": "Sequences homologous to BAV component of HL23V in baboon tissues.", "content": "The BAV component of HL23V virus (HL23V-BAB) hybridized to DNA from different Baboon tissues and appears to be an endogenous Baboon virus. Competition hybridization studies show that HL23V-BAB is closely related to viruses isolated from various Baboon species: P. hamadrys, P. papio, and P. cynocephalus. Competition hybridization studies also show that normal Baboon tissues contain more copies of proviral DNA than cells infected in vitro.", "contents": "Sequences homologous to BAV component of HL23V in baboon tissues. The BAV component of HL23V virus (HL23V-BAB) hybridized to DNA from different Baboon tissues and appears to be an endogenous Baboon virus. Competition hybridization studies show that HL23V-BAB is closely related to viruses isolated from various Baboon species: P. hamadrys, P. papio, and P. cynocephalus. Competition hybridization studies also show that normal Baboon tissues contain more copies of proviral DNA than cells infected in vitro."}
{"id": "PMID:222083", "title": "Density-dependent growth inhibiting interactions between 3T3 and SV40-3T3 cells in mixed cultures.", "content": "3T3 cells are shown to reduce SV40-3T3 cell population growth in a denisty-dependent manner in co-cultures of 3T3 and SV40-3T3 cells. The development of this inhibitory activity roughly parallels the development of density-dependent inhibition of growth in homogeneous 3T3 control cultures. The extent of reduction of SV40-3T3 growth can be manipulated by pretreatment of 3T3 cells with a high serum concentration. SV40-3T3 growth rates are reduced by factors between 10 and 20 under optimum inhibitory conditions as compared to SV40-3T3 growth in control cultures.", "contents": "Density-dependent growth inhibiting interactions between 3T3 and SV40-3T3 cells in mixed cultures. 3T3 cells are shown to reduce SV40-3T3 cell population growth in a denisty-dependent manner in co-cultures of 3T3 and SV40-3T3 cells. The development of this inhibitory activity roughly parallels the development of density-dependent inhibition of growth in homogeneous 3T3 control cultures. The extent of reduction of SV40-3T3 growth can be manipulated by pretreatment of 3T3 cells with a high serum concentration. SV40-3T3 growth rates are reduced by factors between 10 and 20 under optimum inhibitory conditions as compared to SV40-3T3 growth in control cultures."}
{"id": "PMID:222084", "title": "Density-dependent growth adaptation kinetics in 3T3 cell populations following sudden [Ca2+] and temperature changes. A comparison with SV40-3T3 cells.", "content": "Lowered extracellular [Ca2+] cause low growth rates and low stationary cell densities in 3T3 cell cultures as compared to physiological [Ca2%]. Under otherwise constant conditions the extracellular [Ca2+] determines a stable stationary cell density, which can be reached by increase of net cell number or decrease of net cell number, depending on cell density at the time of [Ca2+] adjustment. SV40-3T3 cells do not show this [Ca2+] dependency. At 39 degrees C 3T3 and SV40-3T3 cell populations show an increased growth rate at low cell densities as compared to cell populations at 35 degrees C. Approaching the stationary density the growth rate of both cell sorts is reduced faster at 39 degrees C than at 35 degrees C, leading to lower stationary cell densities at 39 degrees C than at 35 degrees C. A temperature change from 39 degrees C to 35 degrees C or in the opposite direction can affect the stationary cell density of 3T3 cell populations only if applied before reduction of growth rate by density-dependent growth-inhibiting principles has taken place.", "contents": "Density-dependent growth adaptation kinetics in 3T3 cell populations following sudden [Ca2+] and temperature changes. A comparison with SV40-3T3 cells. Lowered extracellular [Ca2+] cause low growth rates and low stationary cell densities in 3T3 cell cultures as compared to physiological [Ca2%]. Under otherwise constant conditions the extracellular [Ca2+] determines a stable stationary cell density, which can be reached by increase of net cell number or decrease of net cell number, depending on cell density at the time of [Ca2+] adjustment. SV40-3T3 cells do not show this [Ca2+] dependency. At 39 degrees C 3T3 and SV40-3T3 cell populations show an increased growth rate at low cell densities as compared to cell populations at 35 degrees C. Approaching the stationary density the growth rate of both cell sorts is reduced faster at 39 degrees C than at 35 degrees C, leading to lower stationary cell densities at 39 degrees C than at 35 degrees C. A temperature change from 39 degrees C to 35 degrees C or in the opposite direction can affect the stationary cell density of 3T3 cell populations only if applied before reduction of growth rate by density-dependent growth-inhibiting principles has taken place."}
{"id": "PMID:222088", "title": "[Dynamics of visual cortex and hippocampal electrical activity during prolonged immobilization].", "content": "As the result of chronic immobilization of rats, their EEG of the visual cortex and hippocampus showed an increased energetic capacity predominantly in the theta-frequency range, a lowered level of synchronization in response to light, reduced sleep duration due to the late falling asleep and waking at different stages. Their sleep became more superficial, the duration of its deeper stages (especially of the paradoxical sleep) decreased, the correlation between the sleep depth and muscular tone and heart-rate was disturbed. The rate of these disorders depended on individual characteristics of the animals nervous system.", "contents": "[Dynamics of visual cortex and hippocampal electrical activity during prolonged immobilization]. As the result of chronic immobilization of rats, their EEG of the visual cortex and hippocampus showed an increased energetic capacity predominantly in the theta-frequency range, a lowered level of synchronization in response to light, reduced sleep duration due to the late falling asleep and waking at different stages. Their sleep became more superficial, the duration of its deeper stages (especially of the paradoxical sleep) decreased, the correlation between the sleep depth and muscular tone and heart-rate was disturbed. The rate of these disorders depended on individual characteristics of the animals nervous system."}
{"id": "PMID:222093", "title": "Detection of enterotoxigenicity and attachment factors in Escherichia coli strains of human, porcine and bovine origin; a comparative study.", "content": "Porcine and bovine strains of E. coli suspected to be enterotoxigenic, were tested for heat-labile enterotoxin (LT) production by means of a test measuring the stimulation of the synthesis of 3151 cyclic adenosin monophosphate (cAMP test) and rounding mouse adrenal tumor Y1 cells (Y1 test), and for heat-stable enterotoxin (ST) production by means of the baby mouse test (BM test). The test results were compared with those of the ligated gut test (LG test) using pig and calf intestine. One hundred and eleven strains of human origin were tested in the cAMP test, the Y1 test and the BM test. All strains were tested for the presence of the attachment factors K88, K99, P987 and CF10407. Seventy-four of 117 bovine strains produced only ST and all 74 ST-producing strains possessed K99 antigen. None of the 43 nonenterotoxigenic strains possessed K99. The presence of K99 antigen is therefore a reliable indicator of enterotoxigenicity in bovine strains. Porcine strains produced LT, ST or LT + ST. The K88 antigen was found in 52 out of 101 enterotoxigenic strains, K99 and P987 in 7 and 6 strains respectively and the latter 13 strains produced only ST. P987 was only detected after subculturing in liquid medium to enhance pilus formation. Eleven out of 111 strains of human origin stimulated cAMP synthesis but failed to round Y1 cells, whereas 4 known LT producers were positive in both tests. Attachment factors were found only in 2 of the latter 4 strains.", "contents": "Detection of enterotoxigenicity and attachment factors in Escherichia coli strains of human, porcine and bovine origin; a comparative study. Porcine and bovine strains of E. coli suspected to be enterotoxigenic, were tested for heat-labile enterotoxin (LT) production by means of a test measuring the stimulation of the synthesis of 3151 cyclic adenosin monophosphate (cAMP test) and rounding mouse adrenal tumor Y1 cells (Y1 test), and for heat-stable enterotoxin (ST) production by means of the baby mouse test (BM test). The test results were compared with those of the ligated gut test (LG test) using pig and calf intestine. One hundred and eleven strains of human origin were tested in the cAMP test, the Y1 test and the BM test. All strains were tested for the presence of the attachment factors K88, K99, P987 and CF10407. Seventy-four of 117 bovine strains produced only ST and all 74 ST-producing strains possessed K99 antigen. None of the 43 nonenterotoxigenic strains possessed K99. The presence of K99 antigen is therefore a reliable indicator of enterotoxigenicity in bovine strains. Porcine strains produced LT, ST or LT + ST. The K88 antigen was found in 52 out of 101 enterotoxigenic strains, K99 and P987 in 7 and 6 strains respectively and the latter 13 strains produced only ST. P987 was only detected after subculturing in liquid medium to enhance pilus formation. Eleven out of 111 strains of human origin stimulated cAMP synthesis but failed to round Y1 cells, whereas 4 known LT producers were positive in both tests. Attachment factors were found only in 2 of the latter 4 strains."}
{"id": "PMID:222089", "title": "[Effect of cholin- and serotoninergic substances on self stimulation in rats].", "content": "The influence of choline- and serotoninergic agents on the pedal self-stimulation (SS) was studied in male rats of Wistar line. Physostigmine decreased the frequency of pressing on the pedal whereas fluoxetine didn't influence SS. Scopolamine activated SS and lowered the threshold of the SS-reaction. P-chloroamphetamine effect depended on the action phase of the drug and was manifested both in depression and activation of SS. Preliminary administration of fluoxetine decreased the activating effect of scopolamine and enhanced the depressing effect of physostigmine. A combination of p-chloroamphetamine and cholinergic agents was accompanied by a tendency toward weakening of depressing effect of physostigmine and toward enhancing of activating effect of scopolamine. It is suggested that serotoninergic mechanisms in case of changes in activity of cholinergic processes, depress the system of positive reinforcement. A functional interaction of choline- and serotoninergic neurotransmitter systems seems probable.", "contents": "[Effect of cholin- and serotoninergic substances on self stimulation in rats]. The influence of choline- and serotoninergic agents on the pedal self-stimulation (SS) was studied in male rats of Wistar line. Physostigmine decreased the frequency of pressing on the pedal whereas fluoxetine didn't influence SS. Scopolamine activated SS and lowered the threshold of the SS-reaction. P-chloroamphetamine effect depended on the action phase of the drug and was manifested both in depression and activation of SS. Preliminary administration of fluoxetine decreased the activating effect of scopolamine and enhanced the depressing effect of physostigmine. A combination of p-chloroamphetamine and cholinergic agents was accompanied by a tendency toward weakening of depressing effect of physostigmine and toward enhancing of activating effect of scopolamine. It is suggested that serotoninergic mechanisms in case of changes in activity of cholinergic processes, depress the system of positive reinforcement. A functional interaction of choline- and serotoninergic neurotransmitter systems seems probable."}
{"id": "PMID:222094", "title": "[Neurological disorders in endometriosis].", "content": "A long-term study of 324 females with endometriosis aged 20--52 years permitted to systematize some syndromes of neurological disorders, depending upon the localization and stage in the progress of endometriosis. In an active infiltrating extension of endometrioid heterotopy there prevail syndromes of peripheral nervous structure lesions. In the late period pseudoneurotic disorders are encountered. The main principles of treatment are discussed.", "contents": "[Neurological disorders in endometriosis]. A long-term study of 324 females with endometriosis aged 20--52 years permitted to systematize some syndromes of neurological disorders, depending upon the localization and stage in the progress of endometriosis. In an active infiltrating extension of endometrioid heterotopy there prevail syndromes of peripheral nervous structure lesions. In the late period pseudoneurotic disorders are encountered. The main principles of treatment are discussed."}
{"id": "PMID:222091", "title": "[Excitatory neuronal responses developing shortly after application of an electrical stimulus to the cerebral cortex].", "content": "The responses of neurones in the sensorimotor area of the intact cortex and in the neuronally isolated cortical slab to direct electrical stimulation was investigated in unanaesthetized rabbits. By a number of parameters the excitatory response of the units may be divided into several individual reactions which set in at different time periods and are apparently of different nature. It is assumed that the short-latency responses are to a considerable degree due to excitatory input to the units along intracortical pathways. Excitatory responses with a 20 to 40 ms latency, appearing at a period of the so-called inhibitory pause, and postinhibitory excitatory responses reveal a considerable dependence on the input from the subcortical formations, activated in a secondary way by the stimulus applied to the cortex.", "contents": "[Excitatory neuronal responses developing shortly after application of an electrical stimulus to the cerebral cortex]. The responses of neurones in the sensorimotor area of the intact cortex and in the neuronally isolated cortical slab to direct electrical stimulation was investigated in unanaesthetized rabbits. By a number of parameters the excitatory response of the units may be divided into several individual reactions which set in at different time periods and are apparently of different nature. It is assumed that the short-latency responses are to a considerable degree due to excitatory input to the units along intracortical pathways. Excitatory responses with a 20 to 40 ms latency, appearing at a period of the so-called inhibitory pause, and postinhibitory excitatory responses reveal a considerable dependence on the input from the subcortical formations, activated in a secondary way by the stimulus applied to the cortex."}
{"id": "PMID:222092", "title": "[Antidromal action potentials as a manifestation of trace excitation].", "content": "The possibility of occurance of action potentials (AP) in neuronal terminals after preliminary excitation of a cortical area was studied in unanaesthetized, non-immobilized rabbits. It was found that a low-frequency subconvulsive stimulation of the sensorimotor cortex may lead to a spontaneous appearance of AP groups that spread antidromically toward the soma of callosal neurones in the opposite hemisphere. Groups of spontaneous antidromic AP were recorded in the cortex after the disappearance of convulsive activity caused by application of penicillin. It is assumed that the observed phenomena reflect a prolonged retention of increased excitability in the terminals of cortical neurones after the end of electrical stimulation or penicillin action.", "contents": "[Antidromal action potentials as a manifestation of trace excitation]. The possibility of occurance of action potentials (AP) in neuronal terminals after preliminary excitation of a cortical area was studied in unanaesthetized, non-immobilized rabbits. It was found that a low-frequency subconvulsive stimulation of the sensorimotor cortex may lead to a spontaneous appearance of AP groups that spread antidromically toward the soma of callosal neurones in the opposite hemisphere. Groups of spontaneous antidromic AP were recorded in the cortex after the disappearance of convulsive activity caused by application of penicillin. It is assumed that the observed phenomena reflect a prolonged retention of increased excitability in the terminals of cortical neurones after the end of electrical stimulation or penicillin action."}
{"id": "PMID:222097", "title": "Comparison of two tests for heterozygosity in congenital adrenal hyperplasia (CAH).", "content": "The increase of plasma cortisol (F), androstenedione (A), 17 alpha-hydroxy-progesterone (17-OH-P) and testosterone (T) was measured after iv administration of ACTH in heterozygotes for CAH and in controls under two different conditions: Test 1: ACTH stimulation was performed without any particular preparation. Test 2: 1.5 mg of dexamethasone (dex.) was given the evening before the ACTH stimulation. Plasma F, A, 17-OH-P and T were measured by specific radioimmunoassays (RIA). Following ACTH stimulation, the increase of 17-OH-P was significantly higher in CAH-heterozygotes than in controls in both tests (P less than 0.0005). Heterozygotes were characterized by a 17-OH-P increase after ACTH stimulation exceeding the + 2 SD limit of the 17-OH-P increase found in controls. The detection of female heterozygotes was considerably improved by the administration of dex. before testing (test 2). In males, however, a better identification of heterozygotes was obtained without previous administration of dex. (test 1). By these tests, 100% of female (test 2) and 79% of male (test 1) CAH heterozygotes could be correctly identified. There were no significant differences in the levels of F, A and T between heterozygotes and controls except for decreased T levels in test 1 (2P less than 0.01) in most male heterozygotes after ACTH stimulation.", "contents": "Comparison of two tests for heterozygosity in congenital adrenal hyperplasia (CAH). The increase of plasma cortisol (F), androstenedione (A), 17 alpha-hydroxy-progesterone (17-OH-P) and testosterone (T) was measured after iv administration of ACTH in heterozygotes for CAH and in controls under two different conditions: Test 1: ACTH stimulation was performed without any particular preparation. Test 2: 1.5 mg of dexamethasone (dex.) was given the evening before the ACTH stimulation. Plasma F, A, 17-OH-P and T were measured by specific radioimmunoassays (RIA). Following ACTH stimulation, the increase of 17-OH-P was significantly higher in CAH-heterozygotes than in controls in both tests (P less than 0.0005). Heterozygotes were characterized by a 17-OH-P increase after ACTH stimulation exceeding the + 2 SD limit of the 17-OH-P increase found in controls. The detection of female heterozygotes was considerably improved by the administration of dex. before testing (test 2). In males, however, a better identification of heterozygotes was obtained without previous administration of dex. (test 1). By these tests, 100% of female (test 2) and 79% of male (test 1) CAH heterozygotes could be correctly identified. There were no significant differences in the levels of F, A and T between heterozygotes and controls except for decreased T levels in test 1 (2P less than 0.01) in most male heterozygotes after ACTH stimulation."}
{"id": "PMID:222090", "title": "[Mechanisms of habituation of the electroexcitable membranes of cortical neurons].", "content": "Habituation of the cortical neurone response is attended with change in the membrane excitability generating peak potentials. Excitability of spontaneous AP trigger zones increases non-specifically. This is due to a non-specific depolarization shift of the membrane potential during habituation. Excitability of the trigger zones of AP evoked by a monotonous stimulus, decreases: the depolarization critical level shifts in the positive direction and the threshold potential increases. Excitability of the trigger zones of AP elicited by an extrastimulus, enhances: the depolarization critical level shifts in the negative direction and the threshold potential decreases. Excitability changes of trigger zones of evoked AP during habituation are specific, local, reversible and resulting from changed electrogenic properties of the zones: they are underlying the change in the response of the neurone electrically excitable membrane in the process of habituation.", "contents": "[Mechanisms of habituation of the electroexcitable membranes of cortical neurons]. Habituation of the cortical neurone response is attended with change in the membrane excitability generating peak potentials. Excitability of spontaneous AP trigger zones increases non-specifically. This is due to a non-specific depolarization shift of the membrane potential during habituation. Excitability of the trigger zones of AP evoked by a monotonous stimulus, decreases: the depolarization critical level shifts in the positive direction and the threshold potential increases. Excitability of the trigger zones of AP elicited by an extrastimulus, enhances: the depolarization critical level shifts in the negative direction and the threshold potential decreases. Excitability changes of trigger zones of evoked AP during habituation are specific, local, reversible and resulting from changed electrogenic properties of the zones: they are underlying the change in the response of the neurone electrically excitable membrane in the process of habituation."}
{"id": "PMID:222098", "title": "The effect of short-term testosterone treatment in boys with delayed puberty.", "content": "Eight boys with severely delayed puberty without pathological cause were treated for 6 months with testosterone. This resulted in acceleration of skeletal maturation and a marked increase in height and weight. No adverse effects were found on hypothalamic-pituitary and gonadal maturation. Basal LH, FSH and testosterone levels rose to nearly adult values at follow-up within a year and pituitary responsiveness to LH-RH increased markedly.", "contents": "The effect of short-term testosterone treatment in boys with delayed puberty. Eight boys with severely delayed puberty without pathological cause were treated for 6 months with testosterone. This resulted in acceleration of skeletal maturation and a marked increase in height and weight. No adverse effects were found on hypothalamic-pituitary and gonadal maturation. Basal LH, FSH and testosterone levels rose to nearly adult values at follow-up within a year and pituitary responsiveness to LH-RH increased markedly."}
{"id": "PMID:222100", "title": "Restoration of the gonadotrophin response to LH-RH and oestrogen administration in patients after molar abortion.", "content": "The relation of the hypothalamic-pituitary effect on gonadotrophin secretion and the concentration of serum hCG after molar abortion was investigated. Gonadotrophin release after a bolus injection of LH-RH or conjugated oestrogens was observed in 17 women until 5 months after molar abortion. Little if any response of gonadotrophin was observed at a hCG level of 100 mIU/ml or more, but the response of LH and FSH to LH-RH were restored to normal when the serum hCG level decreased to below 100 mIU/ml. A normal response of LH to conjugated oestrogens was observed at a serum hCG level of 20 mIU/ml or less. These findings suggest that a high level of hCG interferes with pituitary gonadotrophin secretion, that the threshold hCG levels for normal responses of gonadotrophins to LH-RH and oestrogen are 100 and 20 mIU/ml, respectively, and that secretion of gonadotrophins is restored even in the presence of a low hCG level.", "contents": "Restoration of the gonadotrophin response to LH-RH and oestrogen administration in patients after molar abortion. The relation of the hypothalamic-pituitary effect on gonadotrophin secretion and the concentration of serum hCG after molar abortion was investigated. Gonadotrophin release after a bolus injection of LH-RH or conjugated oestrogens was observed in 17 women until 5 months after molar abortion. Little if any response of gonadotrophin was observed at a hCG level of 100 mIU/ml or more, but the response of LH and FSH to LH-RH were restored to normal when the serum hCG level decreased to below 100 mIU/ml. A normal response of LH to conjugated oestrogens was observed at a serum hCG level of 20 mIU/ml or less. These findings suggest that a high level of hCG interferes with pituitary gonadotrophin secretion, that the threshold hCG levels for normal responses of gonadotrophins to LH-RH and oestrogen are 100 and 20 mIU/ml, respectively, and that secretion of gonadotrophins is restored even in the presence of a low hCG level."}
{"id": "PMID:222101", "title": "[Morphological liver diagnosis in radiology].", "content": "Based on the experiences incurred in the years 1970 to 1977, this thesis deals with the efficiency of sonography, scintigraphy and angiography as well as such supplementary diagnostic procedures as ERCP, hepatography and computed tomography in circumscribed hepatic processes. Based on the typical clinical findings obtained, recommendations are made on further diagnostic procedures according to the given hospital structure in Austria: 80% of liver metastases and circumscribed space-occupying primary lesions may be diagnosed by sonography in Basic Hospitals (Standardkrankenanstalten) while cystic processes may be excluded. Solitary space-occupying lesions will have to be examined further by scintigraphy and angiography on the next highest level, the General Hospital (Schwerpunktkrankenanstalt). In combined application, diagnostic accuracy increases to 90%. ERCP, hepatography and percutaneous transhepatic cholangiography are used in special clinical cases only. Computed tomography, available in Central Hospitals (University Hospitals), will not replace the other morphological, diagnostic procedures.", "contents": "[Morphological liver diagnosis in radiology]. Based on the experiences incurred in the years 1970 to 1977, this thesis deals with the efficiency of sonography, scintigraphy and angiography as well as such supplementary diagnostic procedures as ERCP, hepatography and computed tomography in circumscribed hepatic processes. Based on the typical clinical findings obtained, recommendations are made on further diagnostic procedures according to the given hospital structure in Austria: 80% of liver metastases and circumscribed space-occupying primary lesions may be diagnosed by sonography in Basic Hospitals (Standardkrankenanstalten) while cystic processes may be excluded. Solitary space-occupying lesions will have to be examined further by scintigraphy and angiography on the next highest level, the General Hospital (Schwerpunktkrankenanstalt). In combined application, diagnostic accuracy increases to 90%. ERCP, hepatography and percutaneous transhepatic cholangiography are used in special clinical cases only. Computed tomography, available in Central Hospitals (University Hospitals), will not replace the other morphological, diagnostic procedures."}
{"id": "PMID:222102", "title": "[Pseudohypoparathyroidism type I and vitamin D therapy].", "content": "In pseudohypoparathyroidism type I pharmacologic dosis of vitamin-D can correct hypocalcemia. Several authors who had investigated vitamin-D-metabolism in these patients, found impaired renal conversion of 25-hydroxyvitamin-D to 1,25-dihydroxy-vitamin-D. Treatment of 2 patients with pseudohypoparathyroidism type I with vitamin-D-3 and 1 alpha-Hydroxycholecalciferol consecutively resulted in a nonuniform response with regard to the normalisation of serum-calcium. This led us to the conclusion that the disturbances of vitamin-D-metabolism in pseudohypoparathyroidism type I is heterogenous.", "contents": "[Pseudohypoparathyroidism type I and vitamin D therapy]. In pseudohypoparathyroidism type I pharmacologic dosis of vitamin-D can correct hypocalcemia. Several authors who had investigated vitamin-D-metabolism in these patients, found impaired renal conversion of 25-hydroxyvitamin-D to 1,25-dihydroxy-vitamin-D. Treatment of 2 patients with pseudohypoparathyroidism type I with vitamin-D-3 and 1 alpha-Hydroxycholecalciferol consecutively resulted in a nonuniform response with regard to the normalisation of serum-calcium. This led us to the conclusion that the disturbances of vitamin-D-metabolism in pseudohypoparathyroidism type I is heterogenous."}
{"id": "PMID:222103", "title": "[Microtransplantation of hormone receptors by cell fusion].", "content": "Defective hormone receptors are cultivated in cell cultures and subsequently reconstituted by, in-vitro cell fusion technique.", "contents": "[Microtransplantation of hormone receptors by cell fusion]. Defective hormone receptors are cultivated in cell cultures and subsequently reconstituted by, in-vitro cell fusion technique."}
{"id": "PMID:222105", "title": "Paths and ways of epilepsy.", "content": "The importance assigned to different brain sites for the initiation and conduction of epileptic activity has changed with times, the significant zones being somehow alternatively the cerebral cortex and various centrencephalic structures. Rather than renew this controversy, the available experimental evidence indicating that for the production of epilepsy, the entire brain, or at least several structures and not only discrete cortical or subcortical focal areas must participate, is critically reviewed.", "contents": "Paths and ways of epilepsy. The importance assigned to different brain sites for the initiation and conduction of epileptic activity has changed with times, the significant zones being somehow alternatively the cerebral cortex and various centrencephalic structures. Rather than renew this controversy, the available experimental evidence indicating that for the production of epilepsy, the entire brain, or at least several structures and not only discrete cortical or subcortical focal areas must participate, is critically reviewed."}
{"id": "PMID:222106", "title": "Analysis of unit pairs in the hippocampus.", "content": "Unit pairs were recorded from dorsal hippocampus in curarized rats injected with physostigmine, during spontaneous activity and stimulation of hippocampal afferents. Interactions between neurons and with the theta (theta) rhythm were investigated with statistical procedures which included: autocorrelations, crossocorrelations, peristimulus-time-histograms (PSTHs) and joint-peristimulus-scatter-diagrams (JPSs). Three types of pairs were found: (1) theta pairs, with rhythmical bursting units phaselocked with theta; (2) non-theta pairs, having non-rhythmical cells; and (3) mixed pairs. Theta pairs showed periodical crossrelation between units which fired in phase or out of phase. Non-theta pairs could interact or not. Many interacting non-theta pairs showed a degree of phaselocking with theta. Mixed pairs were rare, but when interacting they always revealed positive periodical crosscorrelations. Stimulus-elicited phase relationships (reset) and rhythmical interactions within the theta pairs suggest a common source for their rhythmicity and reset. In related non-theta pairs the stimulus usually modified their interactions suggesting loose functional connections.", "contents": "Analysis of unit pairs in the hippocampus. Unit pairs were recorded from dorsal hippocampus in curarized rats injected with physostigmine, during spontaneous activity and stimulation of hippocampal afferents. Interactions between neurons and with the theta (theta) rhythm were investigated with statistical procedures which included: autocorrelations, crossocorrelations, peristimulus-time-histograms (PSTHs) and joint-peristimulus-scatter-diagrams (JPSs). Three types of pairs were found: (1) theta pairs, with rhythmical bursting units phaselocked with theta; (2) non-theta pairs, having non-rhythmical cells; and (3) mixed pairs. Theta pairs showed periodical crossrelation between units which fired in phase or out of phase. Non-theta pairs could interact or not. Many interacting non-theta pairs showed a degree of phaselocking with theta. Mixed pairs were rare, but when interacting they always revealed positive periodical crosscorrelations. Stimulus-elicited phase relationships (reset) and rhythmical interactions within the theta pairs suggest a common source for their rhythmicity and reset. In related non-theta pairs the stimulus usually modified their interactions suggesting loose functional connections."}
{"id": "PMID:222107", "title": "F response and H reflex analysis of physiological unity of gravity and antigravity muscles in man.", "content": "Observational differences between reflex (H reflex) and antidromic (F response) activation of segmental motoneurons by a peripheral electrical stimulus are described. In contrast to H reflexes, the percentage of F responses found after a series of stimuli is directly related to the pick-up field of the recording electrode consistent with this response being due to the variable activation of a small fraction of the available motoneuron pool. Despite the differing physiological mechanisms, both F responses and H reflexes can be used to demonstrate similar relative \"central excitatory states\" for antigravity muscles (i.e. extensors in the lower extremity and flexors in the upper extremity) and their antagonist gravity muscles. H reflexes were elicited not only in their usual location in certain antigravity muscles but also in unusual locations by length/tension changes in agonist and antagonist groups as well as by passive stretch. The data argue for the physiological unity of similarly acting gravity and antigravity muscles as well as supporting a meaningful role of group II afferents in normal segmental motoneuron pool excitability.", "contents": "F response and H reflex analysis of physiological unity of gravity and antigravity muscles in man. Observational differences between reflex (H reflex) and antidromic (F response) activation of segmental motoneurons by a peripheral electrical stimulus are described. In contrast to H reflexes, the percentage of F responses found after a series of stimuli is directly related to the pick-up field of the recording electrode consistent with this response being due to the variable activation of a small fraction of the available motoneuron pool. Despite the differing physiological mechanisms, both F responses and H reflexes can be used to demonstrate similar relative \"central excitatory states\" for antigravity muscles (i.e. extensors in the lower extremity and flexors in the upper extremity) and their antagonist gravity muscles. H reflexes were elicited not only in their usual location in certain antigravity muscles but also in unusual locations by length/tension changes in agonist and antagonist groups as well as by passive stretch. The data argue for the physiological unity of similarly acting gravity and antigravity muscles as well as supporting a meaningful role of group II afferents in normal segmental motoneuron pool excitability."}
{"id": "PMID:222108", "title": "An ultrastructural study of cultured human meningioma cells.", "content": "Ultrastructural alterations in human meningioma cells growth in vitro are reported. In early passages the cells retain some of the characteristic features of the original tumors. These include interdigitations associated with intercellular junctional devices (e.g., desmosomes, gap junctions). However, with repeated subculture these features tend to be less frequent. Typical whorl formations are observed only in primary cultures. The number of cytoplasmic filaments, lipid inclusions and other dense bodies increases with time in culture. Cytoplasmic invaginations into nuclei and the appearance of very large cells become more frequent in repeatedly transferred cultures.", "contents": "An ultrastructural study of cultured human meningioma cells. Ultrastructural alterations in human meningioma cells growth in vitro are reported. In early passages the cells retain some of the characteristic features of the original tumors. These include interdigitations associated with intercellular junctional devices (e.g., desmosomes, gap junctions). However, with repeated subculture these features tend to be less frequent. Typical whorl formations are observed only in primary cultures. The number of cytoplasmic filaments, lipid inclusions and other dense bodies increases with time in culture. Cytoplasmic invaginations into nuclei and the appearance of very large cells become more frequent in repeatedly transferred cultures."}
{"id": "PMID:222109", "title": "Neuritis of the cauda equina, a chronic idiopathic polyradiculoneuritis in the horse.", "content": "Four cases of neuritis of the cauda equina (NCE) were studied by light and electron microscopy. Examination of sacral intradural rootlets revealed inflammatory cell infiltrates and an array of myelinated fiber changes which included myelin stripping by invading mononuclear cells and macrophages, as well as splitting and vesiculation of myelin lamellae without obvious participation by leukocytes. More distally in the extradural roots, there was marked granulomatous inflammation, and demyelinative changes were overshadowed by widespread evidence of irreversible axon damage. In all cases, unusual crystalline inclusions appeared in the endoneurium and sheaths of the rootlets and fascicles. The changes in NCE were compared and contrasted with those observed in acute and chronic inflammatory demyelinative neuropathies.", "contents": "Neuritis of the cauda equina, a chronic idiopathic polyradiculoneuritis in the horse. Four cases of neuritis of the cauda equina (NCE) were studied by light and electron microscopy. Examination of sacral intradural rootlets revealed inflammatory cell infiltrates and an array of myelinated fiber changes which included myelin stripping by invading mononuclear cells and macrophages, as well as splitting and vesiculation of myelin lamellae without obvious participation by leukocytes. More distally in the extradural roots, there was marked granulomatous inflammation, and demyelinative changes were overshadowed by widespread evidence of irreversible axon damage. In all cases, unusual crystalline inclusions appeared in the endoneurium and sheaths of the rootlets and fascicles. The changes in NCE were compared and contrasted with those observed in acute and chronic inflammatory demyelinative neuropathies."}
{"id": "PMID:222110", "title": "Flow cytometric analysis of the DNA distribution in human brain tumors.", "content": "Flow cytofluorometric analysis was used to determine the distribution of the DNA content in cells from selected areas of normal human brain and in benign and malignant brain tumors. Propidium iodide was employed as DNA fluorochrome and the analysis was carried out on a suspension of single cells. Normal, nonstimulated human lymphocytes were used as diploid controls. With nonneoplastic tissue an average of 91% of the cells were diploid (presumably in G0 or G1 stage of the cell cycle). The cells of most benign tumors were mainly diploid (77-98%), nine specimens of pituitary adenomas had large numbers of aneuploid cells. In glioblastoma multiforme the proportion of diploid cells was significantly diminished and polyploid cells were frequently seen. Similar results were obtained in other malignant tumors, with metastatic tumors showing the greatest ploidy variation, which included triploid, tetraploid, and hypertetraploid cells. The analytical method used provides valuable information of significant clinical importance on the DNA distribution in brain tumor cells.", "contents": "Flow cytometric analysis of the DNA distribution in human brain tumors. Flow cytofluorometric analysis was used to determine the distribution of the DNA content in cells from selected areas of normal human brain and in benign and malignant brain tumors. Propidium iodide was employed as DNA fluorochrome and the analysis was carried out on a suspension of single cells. Normal, nonstimulated human lymphocytes were used as diploid controls. With nonneoplastic tissue an average of 91% of the cells were diploid (presumably in G0 or G1 stage of the cell cycle). The cells of most benign tumors were mainly diploid (77-98%), nine specimens of pituitary adenomas had large numbers of aneuploid cells. In glioblastoma multiforme the proportion of diploid cells was significantly diminished and polyploid cells were frequently seen. Similar results were obtained in other malignant tumors, with metastatic tumors showing the greatest ploidy variation, which included triploid, tetraploid, and hypertetraploid cells. The analytical method used provides valuable information of significant clinical importance on the DNA distribution in brain tumor cells."}
{"id": "PMID:222111", "title": "Establishment of a human oligodendroglial cell line.", "content": "A human oligodendroglial cell line has been established from a mixed glioma. Over a period of 22 months, the cell consisted of cells with the morphologic features of such a strong perinuclear halo, dichotomous branching, and a tendency to aggregate and float in the medium. In small aggregates, most cells are bipolar. The cell line also continues to synthetize the S-100 protein specific to neural tissue. The response of this cell line to dibutyryl-cyclic AMP is striking, resulting in a remarkable narrowing and elongation of the cell processes. This cell line could be used for studies on glial differentiation and neuron-glia interaction.", "contents": "Establishment of a human oligodendroglial cell line. A human oligodendroglial cell line has been established from a mixed glioma. Over a period of 22 months, the cell consisted of cells with the morphologic features of such a strong perinuclear halo, dichotomous branching, and a tendency to aggregate and float in the medium. In small aggregates, most cells are bipolar. The cell line also continues to synthetize the S-100 protein specific to neural tissue. The response of this cell line to dibutyryl-cyclic AMP is striking, resulting in a remarkable narrowing and elongation of the cell processes. This cell line could be used for studies on glial differentiation and neuron-glia interaction."}
{"id": "PMID:222112", "title": "Sequence of motor nerve terminal involvement in acrylamide neuropathy.", "content": "Acrylamide neuropathy is characterized by distal multifocal axonal degeneration. In this condition long and large myelinated fibers are affected more than sort and thin fibers. The purpose of the present study was to investigate the sequence of nerve terminal involvement. The study was limited to axons that belonged to one type of neuron, of approximately equal diameter but differing in length. Axon terminals from alpha motor neurons were investigated in five muscles from rats. The results show that the initial motor nerve terminal degeneration is widespread and not restricted to terminals of the longest axons with the largest volumes. It is suggested that the variation in degree of involvement of the motor nerve terminals is determined both by differences between endplates and the regenerative capacity of neurons.", "contents": "Sequence of motor nerve terminal involvement in acrylamide neuropathy. Acrylamide neuropathy is characterized by distal multifocal axonal degeneration. In this condition long and large myelinated fibers are affected more than sort and thin fibers. The purpose of the present study was to investigate the sequence of nerve terminal involvement. The study was limited to axons that belonged to one type of neuron, of approximately equal diameter but differing in length. Axon terminals from alpha motor neurons were investigated in five muscles from rats. The results show that the initial motor nerve terminal degeneration is widespread and not restricted to terminals of the longest axons with the largest volumes. It is suggested that the variation in degree of involvement of the motor nerve terminals is determined both by differences between endplates and the regenerative capacity of neurons."}
{"id": "PMID:222113", "title": "Pathological alterations of ependyma and choroid plexus after experimental cerebral infection of mice with Sendai virus.", "content": "The effects of intracerebral inoculation of Sendai virus into young adult mice were investigated by immunofluorescence, light, and electron microscopy. Immunofluorescence of virus-specific antigens was maximal on the third day after inoculation, revealing infection of leptomeninges, ependyma, and choroid plexus. Histologically, meningitis, ependymitis, and choroiditis occurred between the second and third days. The choroiditis was associated with formation of vacuoles within the cytoplasm of epithelial cells. The vacuoles reached diameters up to 50 micrometer. The ubiquitous vacuolization of plexus epithelia resulted in a honeycomb-like pattern. Opaque viral inclusions were visible within the cytoplasm of choroidal and ependymal epithelium as well as in mononuclear inflammatory cells. On electron microscopy, they were composed of intracytoplasmic nucleocapsid accumulations. Viria lay free between microvilli of plexus epithelial cells, and budding virus structures were observed at cellular surfaces. Occasionally, complete viria occurred in the cytoplasm of plexus epithelial cells and were surrounded by a unit membrane from which they appeared to arise by budding. The formation of this small cavity can be interpreted as the first stage of vacuole formation.", "contents": "Pathological alterations of ependyma and choroid plexus after experimental cerebral infection of mice with Sendai virus. The effects of intracerebral inoculation of Sendai virus into young adult mice were investigated by immunofluorescence, light, and electron microscopy. Immunofluorescence of virus-specific antigens was maximal on the third day after inoculation, revealing infection of leptomeninges, ependyma, and choroid plexus. Histologically, meningitis, ependymitis, and choroiditis occurred between the second and third days. The choroiditis was associated with formation of vacuoles within the cytoplasm of epithelial cells. The vacuoles reached diameters up to 50 micrometer. The ubiquitous vacuolization of plexus epithelia resulted in a honeycomb-like pattern. Opaque viral inclusions were visible within the cytoplasm of choroidal and ependymal epithelium as well as in mononuclear inflammatory cells. On electron microscopy, they were composed of intracytoplasmic nucleocapsid accumulations. Viria lay free between microvilli of plexus epithelial cells, and budding virus structures were observed at cellular surfaces. Occasionally, complete viria occurred in the cytoplasm of plexus epithelial cells and were surrounded by a unit membrane from which they appeared to arise by budding. The formation of this small cavity can be interpreted as the first stage of vacuole formation."}
{"id": "PMID:222115", "title": "A clinicopathological study on soft tissue tumors of the head and neck.", "content": "The present study consists of 651 cases of soft tissue tumors originating in the head and neck area. Among these tumors 628 were benign (96%), while there were only 23 malignant cases (4%). In the benign group hemangiomas showed the highest incidence (47%) followed by tumors of adipose tissue (19%) and those of peripheral nerves (12%). Rare tumors consisted of nodular fascitis, hibernoma, lipoblastomatosis, glomus tumor, granular cell tumor, and chondroma. The majority of cases in the malignant group were either those of muscle origin or blood vessel origin. Excepting for two cases of rhabdomyosarcoma of the embryonal type and two cases of angiosarcoma, all showed recurrence and/or metastasis and terminated in death. Three cases of liposarcoma of either well-differentiated or myxoid type had a good prognosis with all three living for 3 or more years without any recurrence. Other malignant tumors consisted of malignant schwannoma, fibrosarcoma, malignant fibrous histiocytoma, alveolar soft part sarcoma, and chordoma. The age, sex, anatomical location, and differential diagnosis have also been described.", "contents": "A clinicopathological study on soft tissue tumors of the head and neck. The present study consists of 651 cases of soft tissue tumors originating in the head and neck area. Among these tumors 628 were benign (96%), while there were only 23 malignant cases (4%). In the benign group hemangiomas showed the highest incidence (47%) followed by tumors of adipose tissue (19%) and those of peripheral nerves (12%). Rare tumors consisted of nodular fascitis, hibernoma, lipoblastomatosis, glomus tumor, granular cell tumor, and chondroma. The majority of cases in the malignant group were either those of muscle origin or blood vessel origin. Excepting for two cases of rhabdomyosarcoma of the embryonal type and two cases of angiosarcoma, all showed recurrence and/or metastasis and terminated in death. Three cases of liposarcoma of either well-differentiated or myxoid type had a good prognosis with all three living for 3 or more years without any recurrence. Other malignant tumors consisted of malignant schwannoma, fibrosarcoma, malignant fibrous histiocytoma, alveolar soft part sarcoma, and chordoma. The age, sex, anatomical location, and differential diagnosis have also been described."}
{"id": "PMID:222116", "title": "Cystic partially differentiated nephroblastoma and multilocular cyst of the kidney. Report of two cases of so-called multilocular cyst of the kidney.", "content": "Two cases of so-called multilocular cyst of the kidney are presented. Although both cases satisfied all of the criteria which characterize the multilocular cyst of the kidney, one had cystic lesions and neoplastic lesions (nephroblastoma-like lesions) and the other had only cystic lesions and was complicated with hamartoma. We prefer the term \"cystic partially differentiated nephroblastoma\" as the diagnostic term for the former and \"multilocular cyst of the kidney\" for the latter. A study of 40 reported cases of multilocular cystic lesions of the kidney revealed that cases having only cystic lesions were distributed in all ages from 4.5 months to 71 years and that cases having neoplastic lesions were seen in infants from 4 months to 2 years.", "contents": "Cystic partially differentiated nephroblastoma and multilocular cyst of the kidney. Report of two cases of so-called multilocular cyst of the kidney. Two cases of so-called multilocular cyst of the kidney are presented. Although both cases satisfied all of the criteria which characterize the multilocular cyst of the kidney, one had cystic lesions and neoplastic lesions (nephroblastoma-like lesions) and the other had only cystic lesions and was complicated with hamartoma. We prefer the term \"cystic partially differentiated nephroblastoma\" as the diagnostic term for the former and \"multilocular cyst of the kidney\" for the latter. A study of 40 reported cases of multilocular cystic lesions of the kidney revealed that cases having only cystic lesions were distributed in all ages from 4.5 months to 71 years and that cases having neoplastic lesions were seen in infants from 4 months to 2 years."}
{"id": "PMID:222117", "title": "Phosphorylation of endogenous proteins by endogenous protein kinase of density gradient--purified plasma membrane vesicles of Ehrlich cells.", "content": "A phosphorylation of endogenous acceptor protein(s) has been demonstrated to occur in membraneous vesicles prepared from Ehrlich ascites tumour cells. The reaction was catalyzed by endogenous protein kinase in the presence of exogenous (gamma32P)ATP. A considerable increase of the specific protein kinase activity took place when the plasma membrane preparation was subjected to a further gradient centrifugation in Dextran T 150. This was done in the presence of a slightly alkaline phosphate buffer containing Mg-ions which resulted in the formation of a well defined vesicular preparation at density 1.035 in the gradient. The apparent Km and Vmax for the reaction with vesicles and exogenous (gamma32P)ATP were determined and found to be 0.022 mM and 0.23 nmol x mg-1 x 10 min-1, respectively. Neither cyclic AMP nor cyclic GMP did stimulate the protein kinase-catalyzed reaction. Instead, a clear inhibition of the reaction by the cyclic nucleotides was unexpectedly registered. Adenosine at 0.5 mM also inhibited the reaction. Calcium ions were inhibitory at all concentrations tested in the presence of a fixed (gamma32P)ATP/Mg2+ ratio. When Mg-ions were stoichiometrically replaced by Ca-ions practically no activity was observed.", "contents": "Phosphorylation of endogenous proteins by endogenous protein kinase of density gradient--purified plasma membrane vesicles of Ehrlich cells. A phosphorylation of endogenous acceptor protein(s) has been demonstrated to occur in membraneous vesicles prepared from Ehrlich ascites tumour cells. The reaction was catalyzed by endogenous protein kinase in the presence of exogenous (gamma32P)ATP. A considerable increase of the specific protein kinase activity took place when the plasma membrane preparation was subjected to a further gradient centrifugation in Dextran T 150. This was done in the presence of a slightly alkaline phosphate buffer containing Mg-ions which resulted in the formation of a well defined vesicular preparation at density 1.035 in the gradient. The apparent Km and Vmax for the reaction with vesicles and exogenous (gamma32P)ATP were determined and found to be 0.022 mM and 0.23 nmol x mg-1 x 10 min-1, respectively. Neither cyclic AMP nor cyclic GMP did stimulate the protein kinase-catalyzed reaction. Instead, a clear inhibition of the reaction by the cyclic nucleotides was unexpectedly registered. Adenosine at 0.5 mM also inhibited the reaction. Calcium ions were inhibitory at all concentrations tested in the presence of a fixed (gamma32P)ATP/Mg2+ ratio. When Mg-ions were stoichiometrically replaced by Ca-ions practically no activity was observed."}
{"id": "PMID:222118", "title": "Plasma catecholamines, cyclic AMP and metabolic substrates in hemorrhagic shock of the rat. The effect of adrenal demedullation and 6-OH-dopamine treatment.", "content": "Plasma catecholamines, cyclic AMP and metabolic substrates in hemorrhagic shock of rats was studied in 4 groups of animals: 1) Control rats, 2) rats with adrenal demedullation, 3) rats with 6-OH-dopamine induced chemical sympathectomy, and 4) rats with combined demedullation and sympathectomy. The rats were bled to a systemic blood pressure of 35 mmHg. The basal plasma level of noradrenaline (NA), adrenaline (A) and dopamine (DA) in control animals was each about 1 nmol/1. After hemorrhage for 1 h the A levels had reached 50 nmol/l and there was little further rise after 4 h. The rise was eliminated by demedullation but unaffected by sympathectomy. NA levels rose continuously in the control and in the sympathectomized rats. At 1 h the level was about 4 nmol/l and at 4 h about 20 nmol/l. The demedullated rats showed a 3-fold increase in circulating NA, while little or no change was seen in the combined demedullated and sympathectomized rats. DA levels did not change in any of the groups during the first hour, but were markedly elevated after 4 h of hypotension. Cyclic AMP and glucose levels in plasma showed a rapid increase 1 h after hemorrhage and thereafter returned to or below basal values. Demedullation largely prevented the increase, while sympathectomy had no effect. The increase in lactate and pyruvate levels were diminished but not eliminated by either sympathectomy or demedullation. Glycerol levels were unchanged and FFA decreased in all groups of rats. The results show that the adrenal medulla is the dominating source of plasma catecholamines in hemorrhagic shock in rats. The initial increase in plasma glucose and cyclic AMP appear to be largely mediated by adrenal A. The subsequent fall in these parameters and derangement of circulatory homeostasis are not, in the present shock model, primarily due to a failure of catecholamine secretion, but rather to a decreased responsiveness of peripheral tissues to catecholamine stimulation.", "contents": "Plasma catecholamines, cyclic AMP and metabolic substrates in hemorrhagic shock of the rat. The effect of adrenal demedullation and 6-OH-dopamine treatment. Plasma catecholamines, cyclic AMP and metabolic substrates in hemorrhagic shock of rats was studied in 4 groups of animals: 1) Control rats, 2) rats with adrenal demedullation, 3) rats with 6-OH-dopamine induced chemical sympathectomy, and 4) rats with combined demedullation and sympathectomy. The rats were bled to a systemic blood pressure of 35 mmHg. The basal plasma level of noradrenaline (NA), adrenaline (A) and dopamine (DA) in control animals was each about 1 nmol/1. After hemorrhage for 1 h the A levels had reached 50 nmol/l and there was little further rise after 4 h. The rise was eliminated by demedullation but unaffected by sympathectomy. NA levels rose continuously in the control and in the sympathectomized rats. At 1 h the level was about 4 nmol/l and at 4 h about 20 nmol/l. The demedullated rats showed a 3-fold increase in circulating NA, while little or no change was seen in the combined demedullated and sympathectomized rats. DA levels did not change in any of the groups during the first hour, but were markedly elevated after 4 h of hypotension. Cyclic AMP and glucose levels in plasma showed a rapid increase 1 h after hemorrhage and thereafter returned to or below basal values. Demedullation largely prevented the increase, while sympathectomy had no effect. The increase in lactate and pyruvate levels were diminished but not eliminated by either sympathectomy or demedullation. Glycerol levels were unchanged and FFA decreased in all groups of rats. The results show that the adrenal medulla is the dominating source of plasma catecholamines in hemorrhagic shock in rats. The initial increase in plasma glucose and cyclic AMP appear to be largely mediated by adrenal A. The subsequent fall in these parameters and derangement of circulatory homeostasis are not, in the present shock model, primarily due to a failure of catecholamine secretion, but rather to a decreased responsiveness of peripheral tissues to catecholamine stimulation."}
{"id": "PMID:222119", "title": "Reacting ultrastructure of the human oligodendrocyte (a study of cerebral cortex distant to brain tumours).", "content": "Electron microscopical examination of adjacent human cerebral cortex from patients with brain tumour revealed the following morphological distinctive features of the oligodendrocyte: the presence of a diffuse electron dense material, large quantities of free ribosomes or ribosomal rosettes, eccentric nucleus with irregular clumps of chromatin, swollen perinuclear cisterna, extensive cytoplasmic microtubules, well-developed Golgi apparatus opposite the eccentric nuclei, dilated endoplasmic reticulum and mitochondria. The majority of oligodendrocytes contain large indefinable heterogeneous electron-dense structures within their perikaryon or processes. Oligodendrocytes with similar inclusion bodies are seen in the vicinity of capillaries. For these reasons a possible phagocytic activity of the human oligodendrocyte seems likely.", "contents": "Reacting ultrastructure of the human oligodendrocyte (a study of cerebral cortex distant to brain tumours). Electron microscopical examination of adjacent human cerebral cortex from patients with brain tumour revealed the following morphological distinctive features of the oligodendrocyte: the presence of a diffuse electron dense material, large quantities of free ribosomes or ribosomal rosettes, eccentric nucleus with irregular clumps of chromatin, swollen perinuclear cisterna, extensive cytoplasmic microtubules, well-developed Golgi apparatus opposite the eccentric nuclei, dilated endoplasmic reticulum and mitochondria. The majority of oligodendrocytes contain large indefinable heterogeneous electron-dense structures within their perikaryon or processes. Oligodendrocytes with similar inclusion bodies are seen in the vicinity of capillaries. For these reasons a possible phagocytic activity of the human oligodendrocyte seems likely."}
{"id": "PMID:222126", "title": "Improvement in regional ventilation and perfusion after radiotherapy for unresectable carcinoma of the bronchus.", "content": "Ventilation/perfusion scans were obtained in 45 patients with unresectable carcinoma of the bronchus. Of these 45 patients, 35 were reinvestigated shortly after radiotherapy and 17 of them had additional later follow-up studies. Both ventilation and perfusion were always abnormal in the lung affected by the tumor; perfusion was usually more impaired than ventilation. These abnormalities were difficult to detect or to evaluate from the standard chest radiograph. After radiotherapy, ventilation improved in 83% and perfusion in 86% of the patients. This improvement was associated with amelioration of breathlessness, which improved in 74% of the patients. Slow but progressive deterioration of regional ventilation and perfusion were subsequently observed. This was often associated with the development of radiation fibrosis. Spirometric measurements (VC, FEV1) were moderately imparied at the initial assessment (83% and 66% of predicted, respectively), probably due to coexisting chronic airway obstruction, and did not show significant changes after radiotherapy or during the follow-up. Radionuclide studies of regional perfusion and ventilation proved more sensitive and more specific than tests of overall lung function for the functional assessment and follow-up of patients with unresectable carcinoma of the bronchus.", "contents": "Improvement in regional ventilation and perfusion after radiotherapy for unresectable carcinoma of the bronchus. Ventilation/perfusion scans were obtained in 45 patients with unresectable carcinoma of the bronchus. Of these 45 patients, 35 were reinvestigated shortly after radiotherapy and 17 of them had additional later follow-up studies. Both ventilation and perfusion were always abnormal in the lung affected by the tumor; perfusion was usually more impaired than ventilation. These abnormalities were difficult to detect or to evaluate from the standard chest radiograph. After radiotherapy, ventilation improved in 83% and perfusion in 86% of the patients. This improvement was associated with amelioration of breathlessness, which improved in 74% of the patients. Slow but progressive deterioration of regional ventilation and perfusion were subsequently observed. This was often associated with the development of radiation fibrosis. Spirometric measurements (VC, FEV1) were moderately imparied at the initial assessment (83% and 66% of predicted, respectively), probably due to coexisting chronic airway obstruction, and did not show significant changes after radiotherapy or during the follow-up. Radionuclide studies of regional perfusion and ventilation proved more sensitive and more specific than tests of overall lung function for the functional assessment and follow-up of patients with unresectable carcinoma of the bronchus."}
{"id": "PMID:222128", "title": "Doughnut pattern of technetium-99m pyrophosphate myocardial uptake in patients with acute myocardial infarction: a sign of poor long-term prognosis.", "content": "Thirty survivors of acute myocardial infarction with 3+ or 4+ positive technetium-99m pyrophosphate myocardial scintigrams were followed up for 28 +/- 3.1 months (mean +/- standard deviation). Three patient groups were identified from the pattern of radioactive uptake in the scintigram: Group I, 16 patients with focal uptake (anterior in 7, lateral in 2, posterior in 3 and inferior in 4); Group II, 6 patients with anterior myocardial infarction and a doughnut pattern of uptake; Group III, 8 patients with nontransmural myocardial infarction and a diffuse pattern of uptake. Late complications developed in all patients with the doughnut pattern of uptake compared with 43 percent of patients with the focal pattern and 12 percent of patients with the diffuse pattern. After discharge from the hospital, five of six patients with a doughnut pattern of uptake died (mean survival time 9.8 months after the initial myocardial infarction). This mortality rate (83 percent) was significantly greater than that of patients with a focal (mortality rate 6 percent) or diffuse (no mortality) pattern of uptake. The doughnut pattern of technetium-99m pyrophosphate myocardial uptake in patients with acute myocardial infarction appears to identify a subgroup of patients with a very poor long-term prognosis.", "contents": "Doughnut pattern of technetium-99m pyrophosphate myocardial uptake in patients with acute myocardial infarction: a sign of poor long-term prognosis. Thirty survivors of acute myocardial infarction with 3+ or 4+ positive technetium-99m pyrophosphate myocardial scintigrams were followed up for 28 +/- 3.1 months (mean +/- standard deviation). Three patient groups were identified from the pattern of radioactive uptake in the scintigram: Group I, 16 patients with focal uptake (anterior in 7, lateral in 2, posterior in 3 and inferior in 4); Group II, 6 patients with anterior myocardial infarction and a doughnut pattern of uptake; Group III, 8 patients with nontransmural myocardial infarction and a diffuse pattern of uptake. Late complications developed in all patients with the doughnut pattern of uptake compared with 43 percent of patients with the focal pattern and 12 percent of patients with the diffuse pattern. After discharge from the hospital, five of six patients with a doughnut pattern of uptake died (mean survival time 9.8 months after the initial myocardial infarction). This mortality rate (83 percent) was significantly greater than that of patients with a focal (mortality rate 6 percent) or diffuse (no mortality) pattern of uptake. The doughnut pattern of technetium-99m pyrophosphate myocardial uptake in patients with acute myocardial infarction appears to identify a subgroup of patients with a very poor long-term prognosis."}
{"id": "PMID:222129", "title": "Correlation of estrogen receptor levels with histology and cytomorphology in human mammary cancer.", "content": "Histologic and cytomorphologic features of mammary carcinoma have been correlated with estrogen receptor (ER) levels determined by the dextran-coated charcoal (Scatchard) analysis in 51 primary mammary carcinomas. The results were expressed as follows: ER-positive above and ER-negative below 10 fmol/mg protein and ER-rich above and ER-poor below 250 fmol/g tissue for premenopausal patients (750 fmol for postmenopausal patients). Most lobular carcinomas were ER-positive and ER-rich (84.6%). A similarly high percentage (88.9%) of ER-positive and ER-rich determinations was seen in ductal carcinomas with tubular features, whereas only about half of the remaining ductal tumors were ER-positive or ER-rich. The highest ER values were obtained in the lobular carcinomas and in ductal carcinomas with tubular features. Three cytomorphologic indices independent of variation in tumor histology showed a strong correlation with ER values: maximal epithelial cellularity of the tumor (P less than 0.001); cellular size (P less than 0.05); nuclear size (P less than 0.05).", "contents": "Correlation of estrogen receptor levels with histology and cytomorphology in human mammary cancer. Histologic and cytomorphologic features of mammary carcinoma have been correlated with estrogen receptor (ER) levels determined by the dextran-coated charcoal (Scatchard) analysis in 51 primary mammary carcinomas. The results were expressed as follows: ER-positive above and ER-negative below 10 fmol/mg protein and ER-rich above and ER-poor below 250 fmol/g tissue for premenopausal patients (750 fmol for postmenopausal patients). Most lobular carcinomas were ER-positive and ER-rich (84.6%). A similarly high percentage (88.9%) of ER-positive and ER-rich determinations was seen in ductal carcinomas with tubular features, whereas only about half of the remaining ductal tumors were ER-positive or ER-rich. The highest ER values were obtained in the lobular carcinomas and in ductal carcinomas with tubular features. Three cytomorphologic indices independent of variation in tumor histology showed a strong correlation with ER values: maximal epithelial cellularity of the tumor (P less than 0.001); cellular size (P less than 0.05); nuclear size (P less than 0.05)."}
{"id": "PMID:222130", "title": "High-density lipoprotein cholesterol. Significant bias between methods.", "content": "Cholesterol content of the high-density lipoproteins has become of interest in evaluating the risk of development of coronary heart disease. There is an inverse relationship between high-density lipoprotein cholesterol and risk. The authors found a significant bias (11.1 mg/dl; 0.289 mmol/l) in a comparison of a rapid cholesterol oxidase method and the Abell--Kendall method for quantitating high-density lipoprotein cholesterol. The two methods did not differ in the usual range of total serum cholesterol. Since methodology may vary, each laboratory's performance should be assessed prior to use of published risk factor data. The authors then studied normal male and female volunteers aged 20 to 35 years. They conclude that high-density lipoprotein cholesterol is of value as a risk factor indicator in this age group. The relationship of total serum cholesterol to high-density lipoprotein cholesterol was studied. The authors conclude that they are independent indicators. Further, there is a range of efficiency of the high-density lipoprotein lipid-clearing function. Finally, the authors attempted unsuccessfully to predict high-density lipoprotein cholesterol from lipoprotein electrophoresis patterns.", "contents": "High-density lipoprotein cholesterol. Significant bias between methods. Cholesterol content of the high-density lipoproteins has become of interest in evaluating the risk of development of coronary heart disease. There is an inverse relationship between high-density lipoprotein cholesterol and risk. The authors found a significant bias (11.1 mg/dl; 0.289 mmol/l) in a comparison of a rapid cholesterol oxidase method and the Abell--Kendall method for quantitating high-density lipoprotein cholesterol. The two methods did not differ in the usual range of total serum cholesterol. Since methodology may vary, each laboratory's performance should be assessed prior to use of published risk factor data. The authors then studied normal male and female volunteers aged 20 to 35 years. They conclude that high-density lipoprotein cholesterol is of value as a risk factor indicator in this age group. The relationship of total serum cholesterol to high-density lipoprotein cholesterol was studied. The authors conclude that they are independent indicators. Further, there is a range of efficiency of the high-density lipoprotein lipid-clearing function. Finally, the authors attempted unsuccessfully to predict high-density lipoprotein cholesterol from lipoprotein electrophoresis patterns."}
{"id": "PMID:222131", "title": "Immune-complex glomerulonephritis associated with cytomegalovirus infection.", "content": "Histologic and immunopathologic studies were performed at autopsy on the kidneys of a patient in whom hematuria and proteinuria developed in association with cytomegalovirus (CMV) pneumonitis. Light microscopic examination of the kidneys revealed focal mesangial proliferative glomerulonephritis. Immunofluorescent microscopy revealed a granular deposition of IgG, IgA, C3, and C4, mainly in the mesangium. CMV antigens were also demonstrated in a similar immunofluorescent pattern. Glomerulus-bound immunoglobulins were eluted and demonstrated to contain antibodies to CMV antigens. These findings suggest that in some patients who have CMV infection immune-complex glomerulonephritis is induced by glomerular deposition of CMV antigen-antibody complexes.", "contents": "Immune-complex glomerulonephritis associated with cytomegalovirus infection. Histologic and immunopathologic studies were performed at autopsy on the kidneys of a patient in whom hematuria and proteinuria developed in association with cytomegalovirus (CMV) pneumonitis. Light microscopic examination of the kidneys revealed focal mesangial proliferative glomerulonephritis. Immunofluorescent microscopy revealed a granular deposition of IgG, IgA, C3, and C4, mainly in the mesangium. CMV antigens were also demonstrated in a similar immunofluorescent pattern. Glomerulus-bound immunoglobulins were eluted and demonstrated to contain antibodies to CMV antigens. These findings suggest that in some patients who have CMV infection immune-complex glomerulonephritis is induced by glomerular deposition of CMV antigen-antibody complexes."}
{"id": "PMID:222132", "title": "Granular cell tumor of the common bile duct. Case report and review of literature.", "content": "A case of granular cell tumor is reported and the main features of the previously reported cases are summarized. This lesion usually presents in a black woman as a small tumor obstructing the common bile duct and resulting in cholecystitis and/or obstructive jaundice. The cell of origin is still disputed. Local resection with cholecystectomy and choledochoduodenostomy appears to be the treatment of choice.", "contents": "Granular cell tumor of the common bile duct. Case report and review of literature. A case of granular cell tumor is reported and the main features of the previously reported cases are summarized. This lesion usually presents in a black woman as a small tumor obstructing the common bile duct and resulting in cholecystitis and/or obstructive jaundice. The cell of origin is still disputed. Local resection with cholecystectomy and choledochoduodenostomy appears to be the treatment of choice."}
{"id": "PMID:222133", "title": "Hepatic bruits in malignant liver tumors.", "content": "There have been few reports concerning hepatic bruits in malignant liver tumors, especially in those other than hepatocellular carcinoma. Lately we noticed hepatic bruits in several cases of malignant liver tumors. The murmurs were confirmed by sound recordings. In cases of hepatocellular carcinoma the murmurs were continuous or continuous with late systolic accentuation. In a case of cholangiocarcinoma of the liver the murmur was continuous with late systolic accentuation and in a case of metastatic liver carcinoma it was systolic. These murmurs were considered to be caused by various mechanisms and some of them are discussed in this paper. Hepatic bruits would be a useful aid in diagnosing hepatic tumors.", "contents": "Hepatic bruits in malignant liver tumors. There have been few reports concerning hepatic bruits in malignant liver tumors, especially in those other than hepatocellular carcinoma. Lately we noticed hepatic bruits in several cases of malignant liver tumors. The murmurs were confirmed by sound recordings. In cases of hepatocellular carcinoma the murmurs were continuous or continuous with late systolic accentuation. In a case of cholangiocarcinoma of the liver the murmur was continuous with late systolic accentuation and in a case of metastatic liver carcinoma it was systolic. These murmurs were considered to be caused by various mechanisms and some of them are discussed in this paper. Hepatic bruits would be a useful aid in diagnosing hepatic tumors."}
{"id": "PMID:222134", "title": "The association of low levels of HDL cholesterol and arteriographically defined coronary artery disease.", "content": "Epidemiologic studies have found associations between low levels of high density lipoprotein (HDL) cholesterol and increased risk of coronary artery disease, using myocardial infarction or angina pectoris as endpoints. However, since most studies have not correlated HDL cholesterol with the presence, severity, or location of anatomically proven coronary disease, the present study measured HDL cholesterol levels in 483 men and women undergoing coronary arteriography. Consistent and statistically significant trends of decreasing mean HDL cholesterol levels with increasing numbers of diseased coronary arteries were observed in both men and women and in younger and older age groups. Although women without coronary disease had much higher levels of HDL cholesterol than men without coronary disease, the differences between men and women with similar degrees of coronary disease were small. Low levels of HDL cholesterol were associated with left main coronary disease; patients with both triple vessel disease and left main disease had lower levels of HDL cholesterol than did patients with triple vessel disease without left main disease. These results were not explained by the possible associations of low density lipoprotein cholesterol or triglycerides with HDL cholesterol. These findings suggest that low levels of HDL cholesterol are important risk factors for the development of atherosclerosis and that they may be useful for identifying patients at high risk of certain anatomic patterns of coronary artery disease.", "contents": "The association of low levels of HDL cholesterol and arteriographically defined coronary artery disease. Epidemiologic studies have found associations between low levels of high density lipoprotein (HDL) cholesterol and increased risk of coronary artery disease, using myocardial infarction or angina pectoris as endpoints. However, since most studies have not correlated HDL cholesterol with the presence, severity, or location of anatomically proven coronary disease, the present study measured HDL cholesterol levels in 483 men and women undergoing coronary arteriography. Consistent and statistically significant trends of decreasing mean HDL cholesterol levels with increasing numbers of diseased coronary arteries were observed in both men and women and in younger and older age groups. Although women without coronary disease had much higher levels of HDL cholesterol than men without coronary disease, the differences between men and women with similar degrees of coronary disease were small. Low levels of HDL cholesterol were associated with left main coronary disease; patients with both triple vessel disease and left main disease had lower levels of HDL cholesterol than did patients with triple vessel disease without left main disease. These results were not explained by the possible associations of low density lipoprotein cholesterol or triglycerides with HDL cholesterol. These findings suggest that low levels of HDL cholesterol are important risk factors for the development of atherosclerosis and that they may be useful for identifying patients at high risk of certain anatomic patterns of coronary artery disease."}
{"id": "PMID:222135", "title": "High density lipoprotein cholesterol and incidence of coronary heart disease--the Israeli Ischemic Heart Disease Study.", "content": "Using univariate and multivariate analyses, the association between high density lipoprotein (HDL) cholesterol and coronary heart disease (CHD) incidence was investigated. Over 150 cases of myocardial infarction (MI) occurred among 6500 Israeli adult males in a five-year prospective study. At age 50 years and over, there is a significant inverse association between MI incidence and HDL cholesterol. This relationship persists when controlling for risk factors such as age, other cholesterol components, smoking, blood pressure, weight, and diabetes mellitus. Unlike hypercholesterolemia and smoking, the relative risk with HDL cholesterol increases with age above 50. Similar patterns of association occur between HDL cholesterol and angina pectoris incidence, sudden unexpected death and deaths from MI. It is suggested that HDL cholesterol is an independent risk factor for CHD, especially in males over 50, and the implication of this study is that increased HDL cholesterol might play a protective role in the pathogenesis of CHD.", "contents": "High density lipoprotein cholesterol and incidence of coronary heart disease--the Israeli Ischemic Heart Disease Study. Using univariate and multivariate analyses, the association between high density lipoprotein (HDL) cholesterol and coronary heart disease (CHD) incidence was investigated. Over 150 cases of myocardial infarction (MI) occurred among 6500 Israeli adult males in a five-year prospective study. At age 50 years and over, there is a significant inverse association between MI incidence and HDL cholesterol. This relationship persists when controlling for risk factors such as age, other cholesterol components, smoking, blood pressure, weight, and diabetes mellitus. Unlike hypercholesterolemia and smoking, the relative risk with HDL cholesterol increases with age above 50. Similar patterns of association occur between HDL cholesterol and angina pectoris incidence, sudden unexpected death and deaths from MI. It is suggested that HDL cholesterol is an independent risk factor for CHD, especially in males over 50, and the implication of this study is that increased HDL cholesterol might play a protective role in the pathogenesis of CHD."}
{"id": "PMID:222136", "title": "Non-polio enterovirus activity in Wisconsin based on a 20-year experience in a diagnostic virology laboratory.", "content": "Laboratory test results, demographic information, and clinical data on 1364 patients who had specimens submitted to the Wisconsin State Laboratory of Hygiene and from whom non-polio enteroviruses were isolated during 1957--1976 were examined. Echoviruses (echo) and Coxsackievirus group B (CB) and group A (CA) were isolated from 719, 389, and 256 of the patients, respectively. Thirty-five different serotypes were identified in the 20-year period. The six most frequently occurring serotypes (echo 9, CB 5, echo 18, CB 2, CB 4, and echo 6) were associated with 57 per cent of all illnesses. The first three serotypes occurred in an epidemic-like manner whereas the next three appeared to be endemic. Eighty-eight per cent of all isolations were from patients whose illnesses began in July through October. The percentage of CA isolates obtained from adults was much smaller than the corresponding percentages seen with CB or echo. A majority of the non-polio enteroviruses were obtained from males. Central nervous system and gastrointestinal tract involvement was greatest with echo and CB 5 tract and lowest with CA and CB 1--4 illnesses. The highest frequency of respiratory tract involvement was with CA and echo 9 illnesses and rash was most frequent with CA illnesses. The highest frequency of hospitalization was with CB 5 patients.", "contents": "Non-polio enterovirus activity in Wisconsin based on a 20-year experience in a diagnostic virology laboratory. Laboratory test results, demographic information, and clinical data on 1364 patients who had specimens submitted to the Wisconsin State Laboratory of Hygiene and from whom non-polio enteroviruses were isolated during 1957--1976 were examined. Echoviruses (echo) and Coxsackievirus group B (CB) and group A (CA) were isolated from 719, 389, and 256 of the patients, respectively. Thirty-five different serotypes were identified in the 20-year period. The six most frequently occurring serotypes (echo 9, CB 5, echo 18, CB 2, CB 4, and echo 6) were associated with 57 per cent of all illnesses. The first three serotypes occurred in an epidemic-like manner whereas the next three appeared to be endemic. Eighty-eight per cent of all isolations were from patients whose illnesses began in July through October. The percentage of CA isolates obtained from adults was much smaller than the corresponding percentages seen with CB or echo. A majority of the non-polio enteroviruses were obtained from males. Central nervous system and gastrointestinal tract involvement was greatest with echo and CB 5 tract and lowest with CA and CB 1--4 illnesses. The highest frequency of respiratory tract involvement was with CA and echo 9 illnesses and rash was most frequent with CA illnesses. The highest frequency of hospitalization was with CB 5 patients."}
{"id": "PMID:222137", "title": "Risk factors in lip cancer: a questionnaire survey.", "content": "An analysis was made of potential risk factors of cancer of the lip in Finland. The series comprised 290 lip cancer patients, and the controls were 254 patients with squamous cell carcinoma of the skin of the head and neck, all reported to the Finnish Cancer Registry in 1972-1973. The results obtained in a questionnaire survey (response rate, 75%; 54% of the total series) indicated that the male lip cancer patients had engaged in outdoor work and smoking with significantly greater frequency than had the male controls. Together, these two risk factors posed a markedly increased risk (RR = 15.4). However, when the factors were analyzed separately, each excluding the effect of the other, no significant risk could be noted. The male lip cancer patients had recurrent herpetic infections with significantly greater frequency than did the male controls. No significant differences were apparent with respect to urban or rural residence. It is concluded that tobacco smoking and outdoor work probably act together to induce lip cancer. The mode of interaction between these factors and the etiologic role of herpesvirus are discussed.", "contents": "Risk factors in lip cancer: a questionnaire survey. An analysis was made of potential risk factors of cancer of the lip in Finland. The series comprised 290 lip cancer patients, and the controls were 254 patients with squamous cell carcinoma of the skin of the head and neck, all reported to the Finnish Cancer Registry in 1972-1973. The results obtained in a questionnaire survey (response rate, 75%; 54% of the total series) indicated that the male lip cancer patients had engaged in outdoor work and smoking with significantly greater frequency than had the male controls. Together, these two risk factors posed a markedly increased risk (RR = 15.4). However, when the factors were analyzed separately, each excluding the effect of the other, no significant risk could be noted. The male lip cancer patients had recurrent herpetic infections with significantly greater frequency than did the male controls. No significant differences were apparent with respect to urban or rural residence. It is concluded that tobacco smoking and outdoor work probably act together to induce lip cancer. The mode of interaction between these factors and the etiologic role of herpesvirus are discussed."}
{"id": "PMID:222138", "title": "Misclassification and the design of environmental studies.", "content": "Many authors have documented the existence of effects due to misclassification. This paper examines the size of these effects in the context of environmental studies. Misclassification occurs because of the use of surrogate measures of exposure. Misclassification causes relative risks to appear smaller than they are, with larger relative risks being seriously affected. The power of statistical tests is reduced, but not as seriously.", "contents": "Misclassification and the design of environmental studies. Many authors have documented the existence of effects due to misclassification. This paper examines the size of these effects in the context of environmental studies. Misclassification occurs because of the use of surrogate measures of exposure. Misclassification causes relative risks to appear smaller than they are, with larger relative risks being seriously affected. The power of statistical tests is reduced, but not as seriously."}
{"id": "PMID:222140", "title": "Patterns and determinants of conjugated estrogen use.", "content": "In view of the carcinogenic potential and widespread use of conjugated estrogens (CEs), this study evaluated patterns and determinants of oral ambulatory CE use. Among 1273 women 30 to 69 years of age interviewed in Greater-Boston hospitals, there were 161 (13%) ever-users of CEs; 88 (7%) had used the drug within the preceding year. The median duration of use was three years. Prominent determinants of use were age, menopause and history of menopausal symptoms. Physician prescription survey data from an independent source suggest that CE use has been common throughout the United States, and may have declined after the reports linking CEs to endometrial cancer were published in 1975. If CE use indeed increases the risk of endometrial cancer some fivefold, an important public health problem exists.", "contents": "Patterns and determinants of conjugated estrogen use. In view of the carcinogenic potential and widespread use of conjugated estrogens (CEs), this study evaluated patterns and determinants of oral ambulatory CE use. Among 1273 women 30 to 69 years of age interviewed in Greater-Boston hospitals, there were 161 (13%) ever-users of CEs; 88 (7%) had used the drug within the preceding year. The median duration of use was three years. Prominent determinants of use were age, menopause and history of menopausal symptoms. Physician prescription survey data from an independent source suggest that CE use has been common throughout the United States, and may have declined after the reports linking CEs to endometrial cancer were published in 1975. If CE use indeed increases the risk of endometrial cancer some fivefold, an important public health problem exists."}
{"id": "PMID:222141", "title": "Epidemic viral gastroenteritis.", "content": "Epidemic viral gastroenteritis is a significant world wide problem. In developed countries, gastroenteritis accounts for significant morbidity and loss of time from work; in the Third World it is the leading cause of mortality among infants and children. Recent technologic advances have been associated with an explosion of research activity. Two virus groups, the Norwalk-like agents and the rotaviruses, are currently accepted as causative agents of viral gastroenteritis in man. The problem of viral gastroenteritis is reviewed both from a current and a historic perspective.", "contents": "Epidemic viral gastroenteritis. Epidemic viral gastroenteritis is a significant world wide problem. In developed countries, gastroenteritis accounts for significant morbidity and loss of time from work; in the Third World it is the leading cause of mortality among infants and children. Recent technologic advances have been associated with an explosion of research activity. Two virus groups, the Norwalk-like agents and the rotaviruses, are currently accepted as causative agents of viral gastroenteritis in man. The problem of viral gastroenteritis is reviewed both from a current and a historic perspective."}
{"id": "PMID:222143", "title": "Pituitary adrenal recovery following short-term suppression with corticosteroids.", "content": "To provide clinical guidelines for the use of high-dose short-term glucocorticoid therapy, we studied recovery of the hypothalamic-pituitary-adrenal axis in 10 normal men following the administration of suppressive doses of prednisone (25 mg twice daily for five days). Cortisol responses to insulin-induced hypoglycemia and synthetic ACTH before treatment were compared with responses two and five days after concluding the prednisone course when adrenal function was not influenced by the presence of exogenous steroid. Two days after prednisone therapy, peak cortisol responses to both hypoglycemia (11.0 +/- 0.9 microgram/dl mean +/- SEM) and synthetic ACTH (13.3 +/- 1.4 microgram/dl) were significantly reduced compared to pretreatment (20.6 +/- 1.6 and 27.3 +/- 2.5 microgram/dl, respectively, p less than 0.001). Five days after concluding the prednisone therapy, peak cortisol response to hypoglycemia had returned to near pretreatment levels although peak cortisol response in the adrenal gland to synthetic ACTH (22.3 +/- 1.1 microgram/dl) remained reduced (p less than 0.05). These data suggest that brief courses of high-dose prednisone therapy may limit the adrenal component of the hypothalamic-pituitary-adrenal response to stress for up to five days.", "contents": "Pituitary adrenal recovery following short-term suppression with corticosteroids. To provide clinical guidelines for the use of high-dose short-term glucocorticoid therapy, we studied recovery of the hypothalamic-pituitary-adrenal axis in 10 normal men following the administration of suppressive doses of prednisone (25 mg twice daily for five days). Cortisol responses to insulin-induced hypoglycemia and synthetic ACTH before treatment were compared with responses two and five days after concluding the prednisone course when adrenal function was not influenced by the presence of exogenous steroid. Two days after prednisone therapy, peak cortisol responses to both hypoglycemia (11.0 +/- 0.9 microgram/dl mean +/- SEM) and synthetic ACTH (13.3 +/- 1.4 microgram/dl) were significantly reduced compared to pretreatment (20.6 +/- 1.6 and 27.3 +/- 2.5 microgram/dl, respectively, p less than 0.001). Five days after concluding the prednisone therapy, peak cortisol response to hypoglycemia had returned to near pretreatment levels although peak cortisol response in the adrenal gland to synthetic ACTH (22.3 +/- 1.1 microgram/dl) remained reduced (p less than 0.05). These data suggest that brief courses of high-dose prednisone therapy may limit the adrenal component of the hypothalamic-pituitary-adrenal response to stress for up to five days."}
{"id": "PMID:222147", "title": "Do endorphin residues of beta lipotropin in hormone reinforce reproductive functions?", "content": "The beta-endorphin residue of pituitary beta-lipotropin hormone, which regulates utilization and storage of body fat, is several times more potent than morphine in raising pain tolerance. It also produces habituation and dependency behavior. Recently it was found to be present in amniotic fluid and to be a releaser of prolactin. It now appears that the placenta is a rich source of endorphins. These findings may open a new chapter in understanding molecular determinants of behavior patterns responsible for natural selection and survival of vertebrate species. Clinical application of basic information and new concepts relating endorphins to maternal behavior patterns and neonatal physiology is the purpose of this communication. A brief review of the literature, some data from [3H]opiate-binding assays, observation of maternal performance, and reports of maternity patients' feelings and motivations suggesting that these hormone molecules mediate formation of affectional attitude, appetitive systems, and maternal behavior will be presented.", "contents": "Do endorphin residues of beta lipotropin in hormone reinforce reproductive functions? The beta-endorphin residue of pituitary beta-lipotropin hormone, which regulates utilization and storage of body fat, is several times more potent than morphine in raising pain tolerance. It also produces habituation and dependency behavior. Recently it was found to be present in amniotic fluid and to be a releaser of prolactin. It now appears that the placenta is a rich source of endorphins. These findings may open a new chapter in understanding molecular determinants of behavior patterns responsible for natural selection and survival of vertebrate species. Clinical application of basic information and new concepts relating endorphins to maternal behavior patterns and neonatal physiology is the purpose of this communication. A brief review of the literature, some data from [3H]opiate-binding assays, observation of maternal performance, and reports of maternity patients' feelings and motivations suggesting that these hormone molecules mediate formation of affectional attitude, appetitive systems, and maternal behavior will be presented."}
{"id": "PMID:222148", "title": "Prolactin-secreting pituitary adenomas in women. II. Menstrual function, pituitary reserves, and prolactin production following microsurgical removal.", "content": "A prospective study of 46 women with prolactin-secreting pituitary adenomas and amenorrhea and/or galactorrhea was performed to determine the influence of the selective transsphenoidal removal of these tumors on pituitary and reproductive function. This procedure was effective in restoring menstrual function in 34 of 41 women and in eliminating lactation in 30 of 40 women. Tumor size and preoperative serum prolactin concentrations were the most important factors in predicting the postoperative disappearance of symptoms. Normal menstrual function returned in 33 of 34 women with tumors less than 2 cm in diameter but in only one of seven women with tumors greater than 2 cm. Similarly, galactorrhea disappeared in 29 of 34 women with tumors less than 2 cm but in only one of six women with larger tumors. Menses returned in 31 of 32 women and galactorrhea disappeared in 25 of 31 women with preoperative serum prolactin levels below 200 ng/ml; conversely, menses returned in only three of nine women and lactation ceased in one of six women with preoperative serum prolactin concentrations above 200 ng/ml. Prolactin concentrations decreased in 42 of 43 patients following the removal of pituitary adenomas and returned to normal in 30. Postoperative pituitary reserves of adrenocorticotropic hormone, growth hormone, luteinizing hormone, and follicle-stimulating hormone were normal in most patients. These data indicate that the removal of prolactin-secreting pituitary adenomas by a neurosurgeon accomplished in this surgical technique is effective in restoring menstrual function and eliminating lactation in most women, especially if the tumor is less than 2 cm in diameter and the preoperative serum prolactin concentration is less than 200 ng/ml.", "contents": "Prolactin-secreting pituitary adenomas in women. II. Menstrual function, pituitary reserves, and prolactin production following microsurgical removal. A prospective study of 46 women with prolactin-secreting pituitary adenomas and amenorrhea and/or galactorrhea was performed to determine the influence of the selective transsphenoidal removal of these tumors on pituitary and reproductive function. This procedure was effective in restoring menstrual function in 34 of 41 women and in eliminating lactation in 30 of 40 women. Tumor size and preoperative serum prolactin concentrations were the most important factors in predicting the postoperative disappearance of symptoms. Normal menstrual function returned in 33 of 34 women with tumors less than 2 cm in diameter but in only one of seven women with tumors greater than 2 cm. Similarly, galactorrhea disappeared in 29 of 34 women with tumors less than 2 cm but in only one of six women with larger tumors. Menses returned in 31 of 32 women and galactorrhea disappeared in 25 of 31 women with preoperative serum prolactin levels below 200 ng/ml; conversely, menses returned in only three of nine women and lactation ceased in one of six women with preoperative serum prolactin concentrations above 200 ng/ml. Prolactin concentrations decreased in 42 of 43 patients following the removal of pituitary adenomas and returned to normal in 30. Postoperative pituitary reserves of adrenocorticotropic hormone, growth hormone, luteinizing hormone, and follicle-stimulating hormone were normal in most patients. These data indicate that the removal of prolactin-secreting pituitary adenomas by a neurosurgeon accomplished in this surgical technique is effective in restoring menstrual function and eliminating lactation in most women, especially if the tumor is less than 2 cm in diameter and the preoperative serum prolactin concentration is less than 200 ng/ml."}
{"id": "PMID:222149", "title": "Rhegmatogenous retinal detachment complicating cytomegalovirus retinitis.", "content": "Six eyes in four patients with cytomegalovirus retinitis developed retinal holes and retinal detachment. Holes appeared in areas of necrosis and were typically large and round with shaggy edges. Differentiation from exudative detachment was sometimes difficult because of obscuration of the fundus by vitreous haze. Cryotherapy was successful in closing open breaks without detachment; cryotherapy and exoplant surgery were used effectively to treat the initial detachments. The occurrence of massive periretinal proliferation and late development of new areas of hole formation or retinitis complicated therapy for these detachments.", "contents": "Rhegmatogenous retinal detachment complicating cytomegalovirus retinitis. Six eyes in four patients with cytomegalovirus retinitis developed retinal holes and retinal detachment. Holes appeared in areas of necrosis and were typically large and round with shaggy edges. Differentiation from exudative detachment was sometimes difficult because of obscuration of the fundus by vitreous haze. Cryotherapy was successful in closing open breaks without detachment; cryotherapy and exoplant surgery were used effectively to treat the initial detachments. The occurrence of massive periretinal proliferation and late development of new areas of hole formation or retinitis complicated therapy for these detachments."}
{"id": "PMID:222145", "title": "A comparative trial of clofibrate and nicotinyl alcohol tartrate in hyperlipoproteinemic patients.", "content": "The effects of nicotinyl alcohol tartrate (Roniacol) and clofibrate (Atromid-S) on plasma cholesterol, triglycerides and lipoprotein cholesterol concentrations were compared in 19 patients with hyperlipoproteinemia in a 32-week, double-blind, crossover trial. Determination of serum clofibric acid concentrations, used to check compliance, allowed us to detect an error in the order in which the drugs were dispensed. Both drugs decreased (p less than 0.01) plasma cholesterol approximately 17% in patients with type II hyperlipoproteinemia. Nicotinyl alcohol reduced plasma triglycerides by 20% in six and clofibrate in eight of the nine patients with type IV hyperlipoproteinemia, although the mean effect was not statistically significant due to the large variance. Both drugs decreased (p less than 0.02) very low density lipoprotein (VLDL) cholesterol in the type IV patients; however, clofibrate increased (p less than 0.05) low density lipoprotein (LDL) cholesterol, whereas nicotinyl alcohol did not. Neither drug altered high density lipoprotein (HDL) levels significantly. In future studies, the effect of hypolipidemic drugs on the major classes of plasma lipoproteins should be determined in addition to the response of plasma lipids.", "contents": "A comparative trial of clofibrate and nicotinyl alcohol tartrate in hyperlipoproteinemic patients. The effects of nicotinyl alcohol tartrate (Roniacol) and clofibrate (Atromid-S) on plasma cholesterol, triglycerides and lipoprotein cholesterol concentrations were compared in 19 patients with hyperlipoproteinemia in a 32-week, double-blind, crossover trial. Determination of serum clofibric acid concentrations, used to check compliance, allowed us to detect an error in the order in which the drugs were dispensed. Both drugs decreased (p less than 0.01) plasma cholesterol approximately 17% in patients with type II hyperlipoproteinemia. Nicotinyl alcohol reduced plasma triglycerides by 20% in six and clofibrate in eight of the nine patients with type IV hyperlipoproteinemia, although the mean effect was not statistically significant due to the large variance. Both drugs decreased (p less than 0.02) very low density lipoprotein (VLDL) cholesterol in the type IV patients; however, clofibrate increased (p less than 0.05) low density lipoprotein (LDL) cholesterol, whereas nicotinyl alcohol did not. Neither drug altered high density lipoprotein (HDL) levels significantly. In future studies, the effect of hypolipidemic drugs on the major classes of plasma lipoproteins should be determined in addition to the response of plasma lipids."}
{"id": "PMID:222150", "title": "The sensitivity and heterogeneity of histochemical markers for altered foci involved in liver carcinogenesis.", "content": "Subcutaneous injection of iron dextran resulted in a hepatic siderosis within 2 weeks in rats, as previously reported for mice. Hepatic carcinomas as well as neoplastic nodules in rats were entirely or mainly free of stainable iron and, thus, could be readily identified histologically. In addition, early carcinogen-induced altered foci were resistant to iron accumulation. In rats fed 0.02% N-2-fluorenylacetamide (FAA) for 13 weeks, the number of iron-resistant foci identified following iron injection was the same as that observed with dietary iron overload. Histochemical investigation of enzymatic markers that have been used to identify foci in rats revealed that foci characterized by enzymatic reactions of positive gamma-glutamyl transpeptidase and decreased adenosine triphosphatase and glucose-6-phosphatase corresponded to those characterized by resistance to iron accumulation. However, in quantitative analysis of the early carcinogen-induced foci in rats given iron dextran following a diet containing 0.02% 2-FAA for 13 weeks, more lesions were detected by resistance to iron accumulation than by any of these other properties. There was considerable phenotypic heterogeneity among foci for the enzyme markers. It is concluded that resistance to iron accumulation is a more sensitive and reliable marker for early carcinogen-induced altered hepatocellular foci than is any other histochemical property.", "contents": "The sensitivity and heterogeneity of histochemical markers for altered foci involved in liver carcinogenesis. Subcutaneous injection of iron dextran resulted in a hepatic siderosis within 2 weeks in rats, as previously reported for mice. Hepatic carcinomas as well as neoplastic nodules in rats were entirely or mainly free of stainable iron and, thus, could be readily identified histologically. In addition, early carcinogen-induced altered foci were resistant to iron accumulation. In rats fed 0.02% N-2-fluorenylacetamide (FAA) for 13 weeks, the number of iron-resistant foci identified following iron injection was the same as that observed with dietary iron overload. Histochemical investigation of enzymatic markers that have been used to identify foci in rats revealed that foci characterized by enzymatic reactions of positive gamma-glutamyl transpeptidase and decreased adenosine triphosphatase and glucose-6-phosphatase corresponded to those characterized by resistance to iron accumulation. However, in quantitative analysis of the early carcinogen-induced foci in rats given iron dextran following a diet containing 0.02% 2-FAA for 13 weeks, more lesions were detected by resistance to iron accumulation than by any of these other properties. There was considerable phenotypic heterogeneity among foci for the enzyme markers. It is concluded that resistance to iron accumulation is a more sensitive and reliable marker for early carcinogen-induced altered hepatocellular foci than is any other histochemical property."}
{"id": "PMID:222151", "title": "Rabbit cardiomyopathy associated with a virus antigenically related to human coronavirus strain 229E.", "content": "A new disease of rabbits is described. Following an acute febrile course, animals die or recover by the 11th day postinoculation. The characteristic pathologic finding is multifocal myocardial degeneration and necrosis. The disease can be transmitted by various routes with tissue filtrates or with infectious sera diluted to 10(-6) and passed through 0.1 micron filters. Virus particles with morphologic features characteristic of a coronavirus are present in infectious but not in normal rabbit serums. The antigen(s) in the infectious serums cross-reacts with the 229E and the OC43 strains of human coronavirus. Antigen cross-reacting with the 229E virus is detectable by immunofluorescent staining in frozen sections of heart tissue from sick but not from healthy animals. Animals surviving infection seroconvert to coronavirus specificity, as demonstrated by the presence in convalescent serums of antibody capable of reacting with the 339E virus. Susceptibility to infection has not been demonstrated in mice, hamsters, or guinea pigs, and the virus was not adapted for growth in tissue culture. It is uncertain whether the agent is a natural pathogen of rabbits or a coronavirus contaminant from another species, possibly human. The name rabbit infectious cardiomyopathy is suggested for this disease.", "contents": "Rabbit cardiomyopathy associated with a virus antigenically related to human coronavirus strain 229E. A new disease of rabbits is described. Following an acute febrile course, animals die or recover by the 11th day postinoculation. The characteristic pathologic finding is multifocal myocardial degeneration and necrosis. The disease can be transmitted by various routes with tissue filtrates or with infectious sera diluted to 10(-6) and passed through 0.1 micron filters. Virus particles with morphologic features characteristic of a coronavirus are present in infectious but not in normal rabbit serums. The antigen(s) in the infectious serums cross-reacts with the 229E and the OC43 strains of human coronavirus. Antigen cross-reacting with the 229E virus is detectable by immunofluorescent staining in frozen sections of heart tissue from sick but not from healthy animals. Animals surviving infection seroconvert to coronavirus specificity, as demonstrated by the presence in convalescent serums of antibody capable of reacting with the 339E virus. Susceptibility to infection has not been demonstrated in mice, hamsters, or guinea pigs, and the virus was not adapted for growth in tissue culture. It is uncertain whether the agent is a natural pathogen of rabbits or a coronavirus contaminant from another species, possibly human. The name rabbit infectious cardiomyopathy is suggested for this disease."}
{"id": "PMID:222152", "title": "Mental status, functioning, and stress in chronic schizophrenic patients in communicity care.", "content": "The author studied the interactions between functioning, stress, and psychological deficit, variables considered essential to the schizophrenic patient's adjustment in the community. The results indicate that comprehensive measurement of functioning and stress correlates significantly with mental status. A breakdown by the components of functioning and stress revealed further areas of interaction between these variables. An important finding was that anxiety contributed maximally to the prediction of stress and depression to that of functioning. These data seem relevant to the schizophrenic patient's degree of social adjustment in the community.", "contents": "Mental status, functioning, and stress in chronic schizophrenic patients in communicity care. The author studied the interactions between functioning, stress, and psychological deficit, variables considered essential to the schizophrenic patient's adjustment in the community. The results indicate that comprehensive measurement of functioning and stress correlates significantly with mental status. A breakdown by the components of functioning and stress revealed further areas of interaction between these variables. An important finding was that anxiety contributed maximally to the prediction of stress and depression to that of functioning. These data seem relevant to the schizophrenic patient's degree of social adjustment in the community."}
{"id": "PMID:222153", "title": "Riboflavin requirement for the cultivation of axenic Entamoeba histolytica.", "content": "Riboflavin was found to be essential for the cultivation of axenic Entamoeba histolytica. This is the first demonstration of a flavin requirement by the organism. Panmede, the principal source of flavins in the axenic medium, was treated with activated carbon to remove flavins. Medium made with this flavin-deficient Panmede, and supplemented with ribonucleic acid failed to support the multiplication of amebae in serial subculture, but did so when riboflavin was added. The concentration of riboflavin required to achieve maximal growth was about 1.3 microgram per ml medium. Studies on riboflavin uptake revealed that amebae lack a high-affinity transport system for this vitamin. The rate of riboflavin uptake was equivalent to the rate of pinocytotic uptake of fluid as previously determined.", "contents": "Riboflavin requirement for the cultivation of axenic Entamoeba histolytica. Riboflavin was found to be essential for the cultivation of axenic Entamoeba histolytica. This is the first demonstration of a flavin requirement by the organism. Panmede, the principal source of flavins in the axenic medium, was treated with activated carbon to remove flavins. Medium made with this flavin-deficient Panmede, and supplemented with ribonucleic acid failed to support the multiplication of amebae in serial subculture, but did so when riboflavin was added. The concentration of riboflavin required to achieve maximal growth was about 1.3 microgram per ml medium. Studies on riboflavin uptake revealed that amebae lack a high-affinity transport system for this vitamin. The rate of riboflavin uptake was equivalent to the rate of pinocytotic uptake of fluid as previously determined."}
{"id": "PMID:222154", "title": "The serologic response of hamsters to experimental liver inoculations with Entamoeba histolytica as measured by indirect hemagglutination test and enzyme linked immunosorbent assay.", "content": "Results of testing 298 sera from hamsters inoculated in the liver with Entamoeba histolytica and from 25 uninoculated controls by indirect hemagglutination (IHA) and enzyme linked immunosorbent assay (ELISA) showed that measurable amounts of antibody appeared as early as 5 days after inoculation, generally increased to a high level within 20 days, and persisted for the duration of the experiments (58 days). There was fair correlation between size of liver lesion and titers. Strain differences in amebae used for antigen and for inoculation could not be detected by either test. The IHA test appeared to be very sensitive, and titers of 1:16 and above were specific. With the ELISA technique, it was tentatively concluded that titers of 1:32 were specific for anti-amebic antibodies but only those of 1:128 and above were indicative of liver infections in the experimentally infected hamsters.", "contents": "The serologic response of hamsters to experimental liver inoculations with Entamoeba histolytica as measured by indirect hemagglutination test and enzyme linked immunosorbent assay. Results of testing 298 sera from hamsters inoculated in the liver with Entamoeba histolytica and from 25 uninoculated controls by indirect hemagglutination (IHA) and enzyme linked immunosorbent assay (ELISA) showed that measurable amounts of antibody appeared as early as 5 days after inoculation, generally increased to a high level within 20 days, and persisted for the duration of the experiments (58 days). There was fair correlation between size of liver lesion and titers. Strain differences in amebae used for antigen and for inoculation could not be detected by either test. The IHA test appeared to be very sensitive, and titers of 1:16 and above were specific. With the ELISA technique, it was tentatively concluded that titers of 1:32 were specific for anti-amebic antibodies but only those of 1:128 and above were indicative of liver infections in the experimentally infected hamsters."}
{"id": "PMID:222155", "title": "Diarrhea associated with rotavirus in rural Guatemala: a longitudinal study of 24 infants and young children.", "content": "A population of 24 infants and young children followed prospectively during the first 3 years of life was studied for the occurrence of rotavirus infection by using enzyme-linked immunosorbent assay to detect virus in stools. Infection with rotavirus was associated with 26 (14.2%) of 183 selected diarrheal episodes. Twenty of the 24 infants and young children had diarrhea associated with rotavirus on at least one occasion and six had two such episodes. Rotavirus infection was documented in over 50% of the dehydrating episodes studied, thus further indicating the importance of rotavirus in this population.", "contents": "Diarrhea associated with rotavirus in rural Guatemala: a longitudinal study of 24 infants and young children. A population of 24 infants and young children followed prospectively during the first 3 years of life was studied for the occurrence of rotavirus infection by using enzyme-linked immunosorbent assay to detect virus in stools. Infection with rotavirus was associated with 26 (14.2%) of 183 selected diarrheal episodes. Twenty of the 24 infants and young children had diarrhea associated with rotavirus on at least one occasion and six had two such episodes. Rotavirus infection was documented in over 50% of the dehydrating episodes studied, thus further indicating the importance of rotavirus in this population."}
{"id": "PMID:222156", "title": "Ten clinical cases of human infection with venezuelan equine encephalomyelitis virus, subtype I-D.", "content": "The clinical and laboratory findings in ten humans infected with Venezuelan equine encephalitis virus, subtype I-D, are described in this report. Clinical and laboratory data indicate that, in contrast to equine infections, human infection with these enzootic virus strains (I-D) is similar to human infection with epizootic strains (I-ABC). In most cases there was an abrupt onset of fever, muscle pain, and vomiting. Virus was recovered from sera obtained during the first 3 days of illness. Lymphopenia occurred in all patients, and neutropenia occurred in three. No sequelae of these infections were apparent.", "contents": "Ten clinical cases of human infection with venezuelan equine encephalomyelitis virus, subtype I-D. The clinical and laboratory findings in ten humans infected with Venezuelan equine encephalitis virus, subtype I-D, are described in this report. Clinical and laboratory data indicate that, in contrast to equine infections, human infection with these enzootic virus strains (I-D) is similar to human infection with epizootic strains (I-ABC). In most cases there was an abrupt onset of fever, muscle pain, and vomiting. Virus was recovered from sera obtained during the first 3 days of illness. Lymphopenia occurred in all patients, and neutropenia occurred in three. No sequelae of these infections were apparent."}
{"id": "PMID:222157", "title": "Cutaneous leishmaniasis--a case with persistent organisms after treatment in presence of normal immune response.", "content": "A Peace Corps volunteer in Senegal, West Africa contracted cutaneous leishmaniasis which had several noteworthy features. One of the three presenting cutaneous ulcers was associated with subcutaneous nodules and viable organisms were recovered from healing lesions after multiple courses of treatment, including amphotericin B. Yet, the patient was found to exhibit both humoral and cell mediated features of normal immunologic responsiveness. Ultimately, clinical and parasitological cure occurred. The patient's organism was found to produce lesions in the foot pads of mice.", "contents": "Cutaneous leishmaniasis--a case with persistent organisms after treatment in presence of normal immune response. A Peace Corps volunteer in Senegal, West Africa contracted cutaneous leishmaniasis which had several noteworthy features. One of the three presenting cutaneous ulcers was associated with subcutaneous nodules and viable organisms were recovered from healing lesions after multiple courses of treatment, including amphotericin B. Yet, the patient was found to exhibit both humoral and cell mediated features of normal immunologic responsiveness. Ultimately, clinical and parasitological cure occurred. The patient's organism was found to produce lesions in the foot pads of mice."}
{"id": "PMID:222159", "title": "Arboviruses in New York State: an attempt to determine the role of arboviruses in patients with viral encephalitis and meningitis.", "content": "In a reveiw of 2,963 patients with signs of infections of the central nervous system in New York State in 1966--1977, arboviruses were found to be the confirmed or presumptive etiologic agents in 60 patients. California encephalitis (CE) virus was the most common (44 patients), followed by Powassan (POW) virus (8), St. Louis encephalitis virus (7), and eastern equine encephalitis (EEE) virus (1). Most patients (47) were children. The incidence of encephalitis was higher in patients with arbovirus findings than in infections with any other of the common neurotropic viruses. The disease was fatal in two patients, one infected with POW virus, the other with EEE virus. Most patients with CE virus infections resided in suburban areas. All POW infections were contracted in six rural counties known for their recreational facilities.", "contents": "Arboviruses in New York State: an attempt to determine the role of arboviruses in patients with viral encephalitis and meningitis. In a reveiw of 2,963 patients with signs of infections of the central nervous system in New York State in 1966--1977, arboviruses were found to be the confirmed or presumptive etiologic agents in 60 patients. California encephalitis (CE) virus was the most common (44 patients), followed by Powassan (POW) virus (8), St. Louis encephalitis virus (7), and eastern equine encephalitis (EEE) virus (1). Most patients (47) were children. The incidence of encephalitis was higher in patients with arbovirus findings than in infections with any other of the common neurotropic viruses. The disease was fatal in two patients, one infected with POW virus, the other with EEE virus. Most patients with CE virus infections resided in suburban areas. All POW infections were contracted in six rural counties known for their recreational facilities."}
{"id": "PMID:222160", "title": "Diagnosis of a carotid body chemodectoma with dynamic radionuclide perfusion scanning.", "content": "The first case of a carotid body chemodectoma that was diagnosed using dynamic radionuclide perfusion angiography and subsequently excised is presented. The value of this technic in the investigation of pulsatile tumors is emphasized.", "contents": "Diagnosis of a carotid body chemodectoma with dynamic radionuclide perfusion scanning. The first case of a carotid body chemodectoma that was diagnosed using dynamic radionuclide perfusion angiography and subsequently excised is presented. The value of this technic in the investigation of pulsatile tumors is emphasized."}
{"id": "PMID:222161", "title": "Granular cell myoblastoma involving the common bile duct.", "content": "Three cases of granular cell myoblastoma involving the large bile ducts are reported. Two of the patients were proved to have multifocal tumors. These tumors may clinically simulate sclerosing adenocarcinomas. Technical difficulties with these tumors for the consulting pathologist are discussed.", "contents": "Granular cell myoblastoma involving the common bile duct. Three cases of granular cell myoblastoma involving the large bile ducts are reported. Two of the patients were proved to have multifocal tumors. These tumors may clinically simulate sclerosing adenocarcinomas. Technical difficulties with these tumors for the consulting pathologist are discussed."}
{"id": "PMID:222162", "title": "Gastrinoma associated with common bile duct obstruction and the ectopic production of ACTH.", "content": "A case of adrenocortical hyperfunction due to ectopic production of ACTH by a gastrin-producing tumor of the pancreas is described. Cushing's syndrome preceded the appearance of the overt Zollinger-Ellison syndrome by 2 years and was treated by bilateral adrenalectomy. The Zollinger-Ellison syndrome was initially treated with cimetidine, which successfully reduced the secretion of gastric acid. Because the pancreatic gastrinoma continued to grow, causing obstruction of the common bile duct, biliary diversion and total gastrectomy were performed. There is evidence that the pancreatic gastrinoma was the source of the ectopic production of ACTH and possibly secretion. The role of Histamine-2 blocking agents as therapy in the Zollinger-Ellison syndrome is discussed.", "contents": "Gastrinoma associated with common bile duct obstruction and the ectopic production of ACTH. A case of adrenocortical hyperfunction due to ectopic production of ACTH by a gastrin-producing tumor of the pancreas is described. Cushing's syndrome preceded the appearance of the overt Zollinger-Ellison syndrome by 2 years and was treated by bilateral adrenalectomy. The Zollinger-Ellison syndrome was initially treated with cimetidine, which successfully reduced the secretion of gastric acid. Because the pancreatic gastrinoma continued to grow, causing obstruction of the common bile duct, biliary diversion and total gastrectomy were performed. There is evidence that the pancreatic gastrinoma was the source of the ectopic production of ACTH and possibly secretion. The role of Histamine-2 blocking agents as therapy in the Zollinger-Ellison syndrome is discussed."}
{"id": "PMID:222163", "title": "Long-term treatment with beclomethasone dipropionate aerosol in asthmatic children with special reference to growth.", "content": "Thirty-one children, 19 boys and 12 girls, aged 3.4--10.8 years, with severe perennial bronchial asthma were treated with beclomethasone dipropionate aerosol (BDA) for 16-40 months. The dose was initially 400 micrograms a day and was gradually reduced to the lowest level giving control of symptoms. Earlier steroid or ACTH-treatment in six children was stopped during the BDA-treatment. At the start of the treatment the mean deviation of height compared with normal values for Swedish children was -0.10 s.d. for the boys and -0.51 s.d. for the girls. At the end of the observation period the deviation was -0.22 s.d. and -0.58 s.d., respectively. The increase in deviation was not significant. Bone age was also slightly retarded before beclomethasone treatment but this deviation was not accentuated during the observation period. It is concluded that treatment with BDA does not retard growth or skeletal maturation in children. The number of acute admissions to hospital was reduced by more than 50% during the first year of treatment.", "contents": "Long-term treatment with beclomethasone dipropionate aerosol in asthmatic children with special reference to growth. Thirty-one children, 19 boys and 12 girls, aged 3.4--10.8 years, with severe perennial bronchial asthma were treated with beclomethasone dipropionate aerosol (BDA) for 16-40 months. The dose was initially 400 micrograms a day and was gradually reduced to the lowest level giving control of symptoms. Earlier steroid or ACTH-treatment in six children was stopped during the BDA-treatment. At the start of the treatment the mean deviation of height compared with normal values for Swedish children was -0.10 s.d. for the boys and -0.51 s.d. for the girls. At the end of the observation period the deviation was -0.22 s.d. and -0.58 s.d., respectively. The increase in deviation was not significant. Bone age was also slightly retarded before beclomethasone treatment but this deviation was not accentuated during the observation period. It is concluded that treatment with BDA does not retard growth or skeletal maturation in children. The number of acute admissions to hospital was reduced by more than 50% during the first year of treatment."}
{"id": "PMID:222170", "title": "Changes in the metrial gland of the rat uterus following ovariectomy on day 10 of pregnancy.", "content": "Rats were subjected to ovariectomy or a control operation on day 10 of pregnancy and light and electron microscope studies carried out to examine the cells of the decidua basalis and the mesometrial triangle. Degeneration of the decidua basalis was rapid but proliferation in the mesometrial triangle and differentiation of the typical granulated cells continued for some time, and resulted in the formation of a metrial gland. The earliest effect noted in the metrial gland was the appearance of inclusions in the fibroblast-like stromal cells one day after ovariectomy. During the next four days many stromal cells became packed with a variety of inclusions and it is suggested that some of these may represent phagocytosed cellular debris. Some debris appeared to be in intercellular spaces and was probably derived from granulated cells. Some granulated cells appeared to develop apparently empty vacuoles and this may be a preliminary stage in degeneration. Although granulated cells decreased to become very few in number five days after ovariectomy, the precise mechanism of their loss and the relationship of this to the hormonal environment could not be established.", "contents": "Changes in the metrial gland of the rat uterus following ovariectomy on day 10 of pregnancy. Rats were subjected to ovariectomy or a control operation on day 10 of pregnancy and light and electron microscope studies carried out to examine the cells of the decidua basalis and the mesometrial triangle. Degeneration of the decidua basalis was rapid but proliferation in the mesometrial triangle and differentiation of the typical granulated cells continued for some time, and resulted in the formation of a metrial gland. The earliest effect noted in the metrial gland was the appearance of inclusions in the fibroblast-like stromal cells one day after ovariectomy. During the next four days many stromal cells became packed with a variety of inclusions and it is suggested that some of these may represent phagocytosed cellular debris. Some debris appeared to be in intercellular spaces and was probably derived from granulated cells. Some granulated cells appeared to develop apparently empty vacuoles and this may be a preliminary stage in degeneration. Although granulated cells decreased to become very few in number five days after ovariectomy, the precise mechanism of their loss and the relationship of this to the hormonal environment could not be established."}
{"id": "PMID:222171", "title": "Carcinogenicity of halothane in Swiss/ICR mice.", "content": "A simplified in-vivo bioassay system was used to test the carcinogenic potential of halothane in Swiss/ICR mice. Halothane was tested only at its maximum tolerated dose, and histologic examination was performed only on tumor masses and other grossly abnormal tissues found at necropsy. Two groups, each of 15 timed pregnant mice, were exposed to either halothane, 500 ppm (0.05 per cent), or compressed air for two hours on days 10--19 of pregnancy. Five days after birth the offspring were similarly exposed, three times weekly, for 78 weeks. After a ten-week, no-treatment, observation period, all remaining mice were examined by necropsy. Mice dying or killed in extremis before final sacrifice at 88 weeks of age also underwent complete gross necropsy unless extensive cannibalism or autolysis precluded examination. The incidences of malignant tumors, hepatomas or modular hyperplasias, and benign tumors in halothane-treated mice were 7, 6, and 20 per cent, respectively; there were similar incidences of these lesions in control animals. It is concluded that under the conditions of this experiment, lifetime administration of halothane at its maximum tolerated dose is not associated with an increased incidence of neoplasia in Swiss/ICR mice.", "contents": "Carcinogenicity of halothane in Swiss/ICR mice. A simplified in-vivo bioassay system was used to test the carcinogenic potential of halothane in Swiss/ICR mice. Halothane was tested only at its maximum tolerated dose, and histologic examination was performed only on tumor masses and other grossly abnormal tissues found at necropsy. Two groups, each of 15 timed pregnant mice, were exposed to either halothane, 500 ppm (0.05 per cent), or compressed air for two hours on days 10--19 of pregnancy. Five days after birth the offspring were similarly exposed, three times weekly, for 78 weeks. After a ten-week, no-treatment, observation period, all remaining mice were examined by necropsy. Mice dying or killed in extremis before final sacrifice at 88 weeks of age also underwent complete gross necropsy unless extensive cannibalism or autolysis precluded examination. The incidences of malignant tumors, hepatomas or modular hyperplasias, and benign tumors in halothane-treated mice were 7, 6, and 20 per cent, respectively; there were similar incidences of these lesions in control animals. It is concluded that under the conditions of this experiment, lifetime administration of halothane at its maximum tolerated dose is not associated with an increased incidence of neoplasia in Swiss/ICR mice."}
{"id": "PMID:222173", "title": "An analgesic action of intranvenously administered lidocaine on dorsal-horn neurons responding to noxious thermal stimulation.", "content": "Using extracellular single-unit recording techniques, effects of intravenously administered lidocaine on dorsal-horn nociceptive neurons were studied in cats made decerebrate whose spinal cords had been transected. Thirty-seven neurons in Rexed lamina V responding to high-threshold mechanical and noxious thermal stimuli (radiant heat, using Hardy-Wolff-Goodell dolorimeter) were studied. Lidocaine hydrochloride, 2.5, 5, and 10 mg/kg, iv, produced dose-related suppression of both spontaneous activity and responses of these neurons to noxious thermal stimulation. Spontaneous discharge frequencies at maximum suppression, observed 3--7 min after administration of each of the three doses of lidocaine were 64 +/- 14 (mean +/- 1 SE), 32 +/- 8, and 25 +/- 9 per cent of control values, respectively; responses to noxious thermal stimuli were 83 +/- 5, 52 +/- 8, and 39 +/- 7 per cent of the control values, respectively. Threshold skin temperature to noxious thermal stimulation increased from 44.7 +/- 0.4 C (control) to 46.3 +/- 0.7 C with lidocaine, 5 mg/kg (P less than 0.05), to 47.8 +/- 0.8 C with lidocaine, 10 mg/kg (P less than 0.01). The times necessary for recovery varied in a dose-related fashion. Plasma lidocaine concentrations 5 min after lidocaine, 5 mg/kg, averaged 3.6 +/- 0.7 microgram/ml. These data support the clinical impression that intravenously administered lidocaine produces analgesia at plasma concentrations of 3--10 microgram/ml. It is suggested that lidocaine may block conduction of nociceptive impulses, at least in part, by suppression of spinal-cord nociceptive neurons.", "contents": "An analgesic action of intranvenously administered lidocaine on dorsal-horn neurons responding to noxious thermal stimulation. Using extracellular single-unit recording techniques, effects of intravenously administered lidocaine on dorsal-horn nociceptive neurons were studied in cats made decerebrate whose spinal cords had been transected. Thirty-seven neurons in Rexed lamina V responding to high-threshold mechanical and noxious thermal stimuli (radiant heat, using Hardy-Wolff-Goodell dolorimeter) were studied. Lidocaine hydrochloride, 2.5, 5, and 10 mg/kg, iv, produced dose-related suppression of both spontaneous activity and responses of these neurons to noxious thermal stimulation. Spontaneous discharge frequencies at maximum suppression, observed 3--7 min after administration of each of the three doses of lidocaine were 64 +/- 14 (mean +/- 1 SE), 32 +/- 8, and 25 +/- 9 per cent of control values, respectively; responses to noxious thermal stimuli were 83 +/- 5, 52 +/- 8, and 39 +/- 7 per cent of the control values, respectively. Threshold skin temperature to noxious thermal stimulation increased from 44.7 +/- 0.4 C (control) to 46.3 +/- 0.7 C with lidocaine, 5 mg/kg (P less than 0.05), to 47.8 +/- 0.8 C with lidocaine, 10 mg/kg (P less than 0.01). The times necessary for recovery varied in a dose-related fashion. Plasma lidocaine concentrations 5 min after lidocaine, 5 mg/kg, averaged 3.6 +/- 0.7 microgram/ml. These data support the clinical impression that intravenously administered lidocaine produces analgesia at plasma concentrations of 3--10 microgram/ml. It is suggested that lidocaine may block conduction of nociceptive impulses, at least in part, by suppression of spinal-cord nociceptive neurons."}
{"id": "PMID:222174", "title": "The facial reflex of allergy.", "content": "The facial reflex, originally described by Franz Chvostek, is shown to be of value in allergy by assessing the relative irritability of muscle tissue (cardic, smooth, skeletal) and the effect of certain drugs frequently used by allergists upon them.", "contents": "The facial reflex of allergy. The facial reflex, originally described by Franz Chvostek, is shown to be of value in allergy by assessing the relative irritability of muscle tissue (cardic, smooth, skeletal) and the effect of certain drugs frequently used by allergists upon them."}
{"id": "PMID:222175", "title": "[Fibroadenoma and phyllode tumors. Cytopathological aspect].", "content": "Fibro-adenomas and phyllode tumors of the breast are a classical cause of errors in cyto-diagnosis. On the basis of six personal cases, the authors show that the cytological diagnosis of fibro-adenoma is possible and that there are certain minimal factors which favourise the presence of a phyllode tumour. They emphasize the differential characteristics between fibro-adenomas and carcinomas on the one hand, and between fibro-adenomas and mastitis on the other hand.", "contents": "[Fibroadenoma and phyllode tumors. Cytopathological aspect]. Fibro-adenomas and phyllode tumors of the breast are a classical cause of errors in cyto-diagnosis. On the basis of six personal cases, the authors show that the cytological diagnosis of fibro-adenoma is possible and that there are certain minimal factors which favourise the presence of a phyllode tumour. They emphasize the differential characteristics between fibro-adenomas and carcinomas on the one hand, and between fibro-adenomas and mastitis on the other hand."}
{"id": "PMID:222176", "title": "Humoral and cellular responses in swine exposed to transmissible gastroenteritis virus.", "content": "Swine exposed to attenuated transmissible gastroenteritis virus had higher virus-neutralizing antibody titers than did swine exposed to virulent virus. The cellular response, measured by the direct leukocyte migration-inhibition (LMI) procedure, was greater in swine exposed to virulent virus than in swine exposed to the attenuated virus. Leukocytes from exposed swine were inhibited more in the LMI procedure in the presence of the homologeous sensitizing antigen than in the presence of the heterologous viral antigen. The humoral response measured by virus neutralizing reached a peak 21 days after exposure, and the cellular response measured by LMI reached a peak 28 days after exposure.", "contents": "Humoral and cellular responses in swine exposed to transmissible gastroenteritis virus. Swine exposed to attenuated transmissible gastroenteritis virus had higher virus-neutralizing antibody titers than did swine exposed to virulent virus. The cellular response, measured by the direct leukocyte migration-inhibition (LMI) procedure, was greater in swine exposed to virulent virus than in swine exposed to the attenuated virus. Leukocytes from exposed swine were inhibited more in the LMI procedure in the presence of the homologeous sensitizing antigen than in the presence of the heterologous viral antigen. The humoral response measured by virus neutralizing reached a peak 21 days after exposure, and the cellular response measured by LMI reached a peak 28 days after exposure."}
{"id": "PMID:222179", "title": "Cellular immunity shown in pseudorabies virus-infected pigs by leukocyte migration-inhibition procedure.", "content": "Cellular immunity in pigs inoculated with pseudorabies virus (PRV) was studied by the agarose plate technique of direct leukocyte migration-inhibition procedure. Migration of leukocytes from PRV-infected pigs was inhibited in the presence of PRV antigen, whereas migration of leukocytes from nonexposed pigs was not inhibited in the presence of the same antigen. The migration of leukocytes collected 4 days after intranasal exposure to PRV was inhibited; humoral antibodies could not be detected until 7 days after exposure. Cellular immunity was present in pigs 14 days after inoculation with inactivated PRV antigens; low concentrations of neutralizing and precipitating antibodies were present at this time. The leukocyte migration-inhibiton procedure was found to be a useful tool in studying the role of cellular immunity in PRV infections.", "contents": "Cellular immunity shown in pseudorabies virus-infected pigs by leukocyte migration-inhibition procedure. Cellular immunity in pigs inoculated with pseudorabies virus (PRV) was studied by the agarose plate technique of direct leukocyte migration-inhibition procedure. Migration of leukocytes from PRV-infected pigs was inhibited in the presence of PRV antigen, whereas migration of leukocytes from nonexposed pigs was not inhibited in the presence of the same antigen. The migration of leukocytes collected 4 days after intranasal exposure to PRV was inhibited; humoral antibodies could not be detected until 7 days after exposure. Cellular immunity was present in pigs 14 days after inoculation with inactivated PRV antigens; low concentrations of neutralizing and precipitating antibodies were present at this time. The leukocyte migration-inhibiton procedure was found to be a useful tool in studying the role of cellular immunity in PRV infections."}
{"id": "PMID:222181", "title": "Isolation and culture of endothelial cells from the lungs of small animals.", "content": "Techniques are descirbed for the isolation and culture of endothelial cells from the lungs of small animals. The cells are collected by retrograde perfusion of blood-free lungs with buffered saline containing collagenase. The cells are characterized by light microscopy, electron microscopy of thin sections and surface replicas, and by the presence of angiotensin-converting enzyme (ACE). ACE was assayed using 3H-benzoyl-Phe-Ala-Pro as substrate and was localized by indirect immunofluorescence using guinea pig endothelial cells incubated with rabbit antibodies to guinea pig lung ACE followed by goat anti-rabbit globulins conjugated to fluorescein. Thus, endothelial cultures can be established using small animals commonly employed in studies of pulmonary processing of vasoactive substances.", "contents": "Isolation and culture of endothelial cells from the lungs of small animals. Techniques are descirbed for the isolation and culture of endothelial cells from the lungs of small animals. The cells are collected by retrograde perfusion of blood-free lungs with buffered saline containing collagenase. The cells are characterized by light microscopy, electron microscopy of thin sections and surface replicas, and by the presence of angiotensin-converting enzyme (ACE). ACE was assayed using 3H-benzoyl-Phe-Ala-Pro as substrate and was localized by indirect immunofluorescence using guinea pig endothelial cells incubated with rabbit antibodies to guinea pig lung ACE followed by goat anti-rabbit globulins conjugated to fluorescein. Thus, endothelial cultures can be established using small animals commonly employed in studies of pulmonary processing of vasoactive substances."}
{"id": "PMID:222183", "title": "The structure-activity relationships of halogenated biphenyls as enzyme inducers.", "content": "Polyhalogenated biphenyls induce microsomal mixed-function oxygenases in many species including man. They can be divided into two classes of inducers. 3,4,5,3',4', 5'-Hexa- and 3,4,3',4'-tetrachlorobiphenyls appear to interact with the TCDD receptor, albeit at 100 to 1,000 times the dose. The structure required for 3-MC (TCDD)-type induction seems to be the presence of at least two adjacent halogens in the lateral positions (meta and para) of the benzene rings, and an absence of halogens in the ortho positions adjacent to the biphenyl bridge. It is likely that halogenation of the ortho positions prevents binding by blocking planar configuration. These isomers, although less toxic than TCDD, are much more toxic than other PCB isomers. Most halogenated biphenyl isomers are phenobarbital type inducers or are inactive. The structure-activity relationship for this type of induction is less clear, but active isomers include 2,4,2',4'-tetra-; 2,4,5,2',4',5'-; 2,3,4,2',3',4'-; 2,3,5,2',3'.5'-and 2,4,6,2',4',6'-hexachlorobiphenyls and 2,4,5,2',4',5'-hexabromobiphenyl. The inactivity of many of the lower chlorinated isomers as inducers (mono-through tetrachloro-) may be related to their rapid metabolism. The cytochrome which is induced by commercial PCB and PBB mixtures appears to be identical to a mixture of cytochromes from phenobarbital- and 3-MC-treated rats. These structure-activity relationships suggest that the \"mixed inductive\" effects and much of the toxicity of PCB and PBB mixtures are due to the presence of compounds related structurally to the active chlorinated dibenzofurans or 3,4,3',4'-tetrachlorobiphenyl.", "contents": "The structure-activity relationships of halogenated biphenyls as enzyme inducers. Polyhalogenated biphenyls induce microsomal mixed-function oxygenases in many species including man. They can be divided into two classes of inducers. 3,4,5,3',4', 5'-Hexa- and 3,4,3',4'-tetrachlorobiphenyls appear to interact with the TCDD receptor, albeit at 100 to 1,000 times the dose. The structure required for 3-MC (TCDD)-type induction seems to be the presence of at least two adjacent halogens in the lateral positions (meta and para) of the benzene rings, and an absence of halogens in the ortho positions adjacent to the biphenyl bridge. It is likely that halogenation of the ortho positions prevents binding by blocking planar configuration. These isomers, although less toxic than TCDD, are much more toxic than other PCB isomers. Most halogenated biphenyl isomers are phenobarbital type inducers or are inactive. The structure-activity relationship for this type of induction is less clear, but active isomers include 2,4,2',4'-tetra-; 2,4,5,2',4',5'-; 2,3,4,2',3',4'-; 2,3,5,2',3'.5'-and 2,4,6,2',4',6'-hexachlorobiphenyls and 2,4,5,2',4',5'-hexabromobiphenyl. The inactivity of many of the lower chlorinated isomers as inducers (mono-through tetrachloro-) may be related to their rapid metabolism. The cytochrome which is induced by commercial PCB and PBB mixtures appears to be identical to a mixture of cytochromes from phenobarbital- and 3-MC-treated rats. These structure-activity relationships suggest that the \"mixed inductive\" effects and much of the toxicity of PCB and PBB mixtures are due to the presence of compounds related structurally to the active chlorinated dibenzofurans or 3,4,3',4'-tetrachlorobiphenyl."}
{"id": "PMID:222186", "title": "Cohort study of Michigan residents exposed to polybrominated biphenyls: epidemiologic and immunologic findings.", "content": "Polybrominated biphenyls (PBB) were dispersed widely in Michigan by a 1973 shipping accident in which PBB was introduced into cattle feed. Human exposure resulted principally from ingestion of contaminated dairy food products. To determine whether PBB exposure has or will cause acute or chronic illness, a prospective cohort study of 4545 persons has been undertaken. Three exposure groups were sought; all persons living on PBB-quarantined farms; persons who had received food directly from such farms; workers (and their families) engaged in PBB manufacture. Enrollment rates were 95.6, 95.1 and 78.0%. Also enrolled were 725 persons with low-level PBB exposure. All were queried concerning 17 symptoms and conditions related possibly to PBB. Venous blood was drawn on 3639 and analyzed for PBB by gas chromatography. Mean serum PBB levels were 26.9 ppb in quarantined farm families, 17.1 in recipients, 43.0 ppb in workers, and 3.4 ppb in the low exposure groups. No associations were found between serum PBB levels and symptom prevalence rates. To evaluate peripheral lymphocyte function, T and B cell quantitation and in vitro responses to 3 nonspecific mitogens were studied in 34 persons with highest PBB levels (mean, 787 ppb), and in 56 with low values (mean, 2.8 ppb). No statistically significant differences in lymphocyte number or function were noted.", "contents": "Cohort study of Michigan residents exposed to polybrominated biphenyls: epidemiologic and immunologic findings. Polybrominated biphenyls (PBB) were dispersed widely in Michigan by a 1973 shipping accident in which PBB was introduced into cattle feed. Human exposure resulted principally from ingestion of contaminated dairy food products. To determine whether PBB exposure has or will cause acute or chronic illness, a prospective cohort study of 4545 persons has been undertaken. Three exposure groups were sought; all persons living on PBB-quarantined farms; persons who had received food directly from such farms; workers (and their families) engaged in PBB manufacture. Enrollment rates were 95.6, 95.1 and 78.0%. Also enrolled were 725 persons with low-level PBB exposure. All were queried concerning 17 symptoms and conditions related possibly to PBB. Venous blood was drawn on 3639 and analyzed for PBB by gas chromatography. Mean serum PBB levels were 26.9 ppb in quarantined farm families, 17.1 in recipients, 43.0 ppb in workers, and 3.4 ppb in the low exposure groups. No associations were found between serum PBB levels and symptom prevalence rates. To evaluate peripheral lymphocyte function, T and B cell quantitation and in vitro responses to 3 nonspecific mitogens were studied in 34 persons with highest PBB levels (mean, 787 ppb), and in 56 with low values (mean, 2.8 ppb). No statistically significant differences in lymphocyte number or function were noted."}
{"id": "PMID:222190", "title": "The neurotoxicity of polybrominated biphenyls: results of a medical field survey.", "content": "Neurologic symptoms were the earliest and most prominent symptoms recorded in Michigan farm residents exposed to PBB as compared to a non-PBB exposed control farm population in Wisconsin. In Michigan (particularly among males) those who exhibited the most marked symptoms tended to show diminished performance as assessed by special tests, although population differences in performance were not as marked. Low indices of performance were also significantly correlated with intake of home-produced foodstuffs, particularly during the years 1972--1974 and store-bought products during the years 1975--1976. Between 1972 and 1976 the Michigan farm residents studied made significant changes in their consumption patterns of products suspected to be contaminated with PBB, as compared to those of Wisconsin farm residents. Serum PBB levels were not found to be significantly higher in Michigan males and females exhibiting the most prominent neurologic symptoms. Serum PBB levels were negatively correlated with performance test scores, particularly in males in older age groups.", "contents": "The neurotoxicity of polybrominated biphenyls: results of a medical field survey. Neurologic symptoms were the earliest and most prominent symptoms recorded in Michigan farm residents exposed to PBB as compared to a non-PBB exposed control farm population in Wisconsin. In Michigan (particularly among males) those who exhibited the most marked symptoms tended to show diminished performance as assessed by special tests, although population differences in performance were not as marked. Low indices of performance were also significantly correlated with intake of home-produced foodstuffs, particularly during the years 1972--1974 and store-bought products during the years 1975--1976. Between 1972 and 1976 the Michigan farm residents studied made significant changes in their consumption patterns of products suspected to be contaminated with PBB, as compared to those of Wisconsin farm residents. Serum PBB levels were not found to be significantly higher in Michigan males and females exhibiting the most prominent neurologic symptoms. Serum PBB levels were negatively correlated with performance test scores, particularly in males in older age groups."}
{"id": "PMID:222196", "title": "Immunologic dysfunction among PBB-exposed Michigan dairy farmers.", "content": "In 1973 inadvertent contamination occurred in a special farm feed supplement for lactating cows. Polybrominated biphenyls (PBBs) were used in place of magnesium oxide resulting in serious harm to farm animals, including cattle, chickens, geese, ducks. Farm families, accustomed to eating their own products, were most heavily exposed. To further study the impact of PBBs, 45 adult Michigan farm residents who were originally examined in a clinical field survey were further studied with respect to their immunologic status. For comparison, 46 dairy farm residents in Wisconsin, who had not eaten PBB-contaminated food, were examined, as were 79 healthy subjects in New York City. Abnormalities in the Michigan group included significant decrease in absolute numbers and percentages of T and B-lymphocytes and increased number of lymphocytes with no detectable surface markers (\"null cells\"). Significant reduction of in vitro immune function was noted in 35--40% of the Michigan farm residents who had eaten food containing PBB. Despite the absence of any apparent numerical reduction, both T and B lymphocyte subpopulations of peripheral blood lymphocytes showed evidence of functional defect. Ten of the 45 Michigan farmers studied showed impaired PHA-induced blastogeneic response, due to the decreased number and percent of T-cells in the PBLs. The decreased immune function detected among the PBB-exposed farm residents tended to affect families as a unit and was independent of exposed individuals' age or sex, speaking against the possibility of genetic predisposition.", "contents": "Immunologic dysfunction among PBB-exposed Michigan dairy farmers. In 1973 inadvertent contamination occurred in a special farm feed supplement for lactating cows. Polybrominated biphenyls (PBBs) were used in place of magnesium oxide resulting in serious harm to farm animals, including cattle, chickens, geese, ducks. Farm families, accustomed to eating their own products, were most heavily exposed. To further study the impact of PBBs, 45 adult Michigan farm residents who were originally examined in a clinical field survey were further studied with respect to their immunologic status. For comparison, 46 dairy farm residents in Wisconsin, who had not eaten PBB-contaminated food, were examined, as were 79 healthy subjects in New York City. Abnormalities in the Michigan group included significant decrease in absolute numbers and percentages of T and B-lymphocytes and increased number of lymphocytes with no detectable surface markers (\"null cells\"). Significant reduction of in vitro immune function was noted in 35--40% of the Michigan farm residents who had eaten food containing PBB. Despite the absence of any apparent numerical reduction, both T and B lymphocyte subpopulations of peripheral blood lymphocytes showed evidence of functional defect. Ten of the 45 Michigan farmers studied showed impaired PHA-induced blastogeneic response, due to the decreased number and percent of T-cells in the PBLs. The decreased immune function detected among the PBB-exposed farm residents tended to affect families as a unit and was independent of exposed individuals' age or sex, speaking against the possibility of genetic predisposition."}
{"id": "PMID:222197", "title": "Familial porphyria cutanea tarda in a patient with retinitis pigmentosa.", "content": "The patient in this report had typical retinitis pigmentosa which apparently was of recessive inheritance. In addition, she had an exacerbation of porphyria cutanea tarda (PCT) while taking oral contraceptives. In view of the lack of evidence for hereditary transmission of PCT it is also of interest that the patient's mother had an exacerbation of PCT while taking estrogenic medication.", "contents": "Familial porphyria cutanea tarda in a patient with retinitis pigmentosa. The patient in this report had typical retinitis pigmentosa which apparently was of recessive inheritance. In addition, she had an exacerbation of porphyria cutanea tarda (PCT) while taking oral contraceptives. In view of the lack of evidence for hereditary transmission of PCT it is also of interest that the patient's mother had an exacerbation of PCT while taking estrogenic medication."}
{"id": "PMID:222198", "title": "An overview of pituitary tumors.", "content": "Tumors arising in and around the hypophyseal fossa can cause symptoms by compression of surrounding structures or, in the case of adenomas arising from the adenohypophysis, by hypersecretion of hormones. Until recently, adenomas of the hypophysis have been classified on the basis of light microscopy into chromophobe, eosinophilic and basophilic. Presently available methods of histochemistry, immunocytology, electron microscopy and hormone assays make available a biological classification of these adenomas into two groups: (I) adenomas without secretory activity and (II) adenomas with secretory activity. Amongst the latter are included somatotroph adenomas, prolactin cell adenomas, melanocorticotroph adenomas and thyrotroph adenomas. Many of the large group of tumors formerly called \"chromophobe\" can now be reclassified amongst the secretory adenomas.", "contents": "An overview of pituitary tumors. Tumors arising in and around the hypophyseal fossa can cause symptoms by compression of surrounding structures or, in the case of adenomas arising from the adenohypophysis, by hypersecretion of hormones. Until recently, adenomas of the hypophysis have been classified on the basis of light microscopy into chromophobe, eosinophilic and basophilic. Presently available methods of histochemistry, immunocytology, electron microscopy and hormone assays make available a biological classification of these adenomas into two groups: (I) adenomas without secretory activity and (II) adenomas with secretory activity. Amongst the latter are included somatotroph adenomas, prolactin cell adenomas, melanocorticotroph adenomas and thyrotroph adenomas. Many of the large group of tumors formerly called \"chromophobe\" can now be reclassified amongst the secretory adenomas."}
{"id": "PMID:222204", "title": "A mutant of Saccharomyces cerevisiae lacking catabolic NAD-specific glutamate dehydrogenase. Growth characteristics of the mutant and regulation of enzyme synthesis in the wild-type strain.", "content": "NAD-specific glutamate dehydrogenase (GDH-B) was induced in a wild-type strain derived of alpha-sigma 1278b by alpha-amino acids, the nitrogen of which according to known degradative pathways is transferred to 2-oxoglutarate. A recessive mutant (gdhB) devoid of GDH-B activity grew more slowly than the wild type if one of these amino acids was the sole source of nitrogen. Addition of ammonium chloride, glutamine, asparagine or serine to growth media with inducing alpha-amino acids as the main nitrogen source increased the growth rate of the gdhB mutant to the wild-type level and repressed GDH-B synthesis in the wild type. Arginine, urea and allantoin similarly increased the growth rate of the gdhB mutant and repressed GDH-B synthesis in the presence of glutamate, but not in the presence of aspartate, alanine or proline as the main nitrogen source. These observations are consistent with the view that GDH-B in vivo deaminates glutamate. Ammonium ions are required for the biosynthesis of glutamine, asparagine, arginine, histidine and purine and pyrimidine bases. Aspartate and alanine apparently are more potent inducers of GDH-B than glutamate. Anabolic NADP-specific glutamate dehydrogenase (GDH-A) can not fulfil the function of GDH-B in the gdhB mutant. This is concluded from the equal growth rates in glutamate, aspartate and proline media as observed with a gdhB mutant and with a gdhA, gdhB double mutant in which both glutamate dehydrogenases area lacking. The double mutant showed an anomalous growth behaviour, growth rates on several nitrogen sources being unexpectedly low.", "contents": "A mutant of Saccharomyces cerevisiae lacking catabolic NAD-specific glutamate dehydrogenase. Growth characteristics of the mutant and regulation of enzyme synthesis in the wild-type strain. NAD-specific glutamate dehydrogenase (GDH-B) was induced in a wild-type strain derived of alpha-sigma 1278b by alpha-amino acids, the nitrogen of which according to known degradative pathways is transferred to 2-oxoglutarate. A recessive mutant (gdhB) devoid of GDH-B activity grew more slowly than the wild type if one of these amino acids was the sole source of nitrogen. Addition of ammonium chloride, glutamine, asparagine or serine to growth media with inducing alpha-amino acids as the main nitrogen source increased the growth rate of the gdhB mutant to the wild-type level and repressed GDH-B synthesis in the wild type. Arginine, urea and allantoin similarly increased the growth rate of the gdhB mutant and repressed GDH-B synthesis in the presence of glutamate, but not in the presence of aspartate, alanine or proline as the main nitrogen source. These observations are consistent with the view that GDH-B in vivo deaminates glutamate. Ammonium ions are required for the biosynthesis of glutamine, asparagine, arginine, histidine and purine and pyrimidine bases. Aspartate and alanine apparently are more potent inducers of GDH-B than glutamate. Anabolic NADP-specific glutamate dehydrogenase (GDH-A) can not fulfil the function of GDH-B in the gdhB mutant. This is concluded from the equal growth rates in glutamate, aspartate and proline media as observed with a gdhB mutant and with a gdhA, gdhB double mutant in which both glutamate dehydrogenases area lacking. The double mutant showed an anomalous growth behaviour, growth rates on several nitrogen sources being unexpectedly low."}
{"id": "PMID:222209", "title": "Degradation of poliovirus by adsorption on inorganic surfaces.", "content": "Alteration of the specific infectivity of 3H-labeled ribonucleic acid and 14C-protein labeled poliovirus type 1 by adsorption on inorganic surfaces is investigated by application of kinetic theory to data obtained from sequential extractions of adsorbed virus. Some surfaces, e.g., SiO2, appear to have no significant effect. On the other hand, CuO substantially decreases the specific infectivity of adsorbed preparations. Differences in kinetic plots between 3H-labeled ribonucleic acid and 14C-labeled protein suggest that the inactivation observed involves physical disruption of virions. Van der Waals interactions between solid surfaces and virus are suspected to induce spontaneous virion disassembly. Surface catalyzed disassembly in aquatic and soil environments is implicated as an important mechanism controlling enterovirus dissemination. Methods developed here to evaluate complete recovery of adsorbed virus have potenital application to other degradation studied and problems concerning virus recovery from adsorbents used in virus concentrators.", "contents": "Degradation of poliovirus by adsorption on inorganic surfaces. Alteration of the specific infectivity of 3H-labeled ribonucleic acid and 14C-protein labeled poliovirus type 1 by adsorption on inorganic surfaces is investigated by application of kinetic theory to data obtained from sequential extractions of adsorbed virus. Some surfaces, e.g., SiO2, appear to have no significant effect. On the other hand, CuO substantially decreases the specific infectivity of adsorbed preparations. Differences in kinetic plots between 3H-labeled ribonucleic acid and 14C-labeled protein suggest that the inactivation observed involves physical disruption of virions. Van der Waals interactions between solid surfaces and virus are suspected to induce spontaneous virion disassembly. Surface catalyzed disassembly in aquatic and soil environments is implicated as an important mechanism controlling enterovirus dissemination. Methods developed here to evaluate complete recovery of adsorbed virus have potenital application to other degradation studied and problems concerning virus recovery from adsorbents used in virus concentrators."}
{"id": "PMID:222210", "title": "Human enteroviruses in oysters and their overlying waters.", "content": "The presence of enteroviruses in oysters and oyster-harvesting waters of the Texas Gulf coast was monitored over a period of 10 months. Viruses were detected in water and oyster samples obtained from areas both open and closed to shellfish harvesting. Viruses were detected periodically in waters that met current bacteriological standards for shellfish harvesting. No significant statistical relationship was demonstrated between virus concentration in oysters and the bacteriological and physiochemical quality of water and shellfish. Viruses in water were, however, moderately correlated with total coliforms in water and oysters and with fecal coliforms in oysters. Total coliforms in water were realted to total coliforms in sediment were related only to total coliforms in sediment. Among the physiochemical characteristics of water, turbidity was related statistically to the organic matter content of water and to fecal coliforms in water. There was a marked effect of rainfall on the bacteriological quality of water. Of a total of 44 water samples, 26 yielded virus in concentrations from 4 to 167 plaque-forming units per 100-gallon (ca. 378.5-liter) sample. Of a total of 40 pools of 10 to 12 oysters each, virus was found in 14 pools at a concentration of 6 to 224 plaque-forming units per 100 g of oyster meat. On five occasions, virus was found in water samples when no virus could be detected in oysters harvested from the same sites. This study indicates that current bacteriological standards for determining the safety of shellfish and shellfish-growing waters do no reflect the occurrence of enteroviruses.", "contents": "Human enteroviruses in oysters and their overlying waters. The presence of enteroviruses in oysters and oyster-harvesting waters of the Texas Gulf coast was monitored over a period of 10 months. Viruses were detected in water and oyster samples obtained from areas both open and closed to shellfish harvesting. Viruses were detected periodically in waters that met current bacteriological standards for shellfish harvesting. No significant statistical relationship was demonstrated between virus concentration in oysters and the bacteriological and physiochemical quality of water and shellfish. Viruses in water were, however, moderately correlated with total coliforms in water and oysters and with fecal coliforms in oysters. Total coliforms in water were realted to total coliforms in sediment were related only to total coliforms in sediment. Among the physiochemical characteristics of water, turbidity was related statistically to the organic matter content of water and to fecal coliforms in water. There was a marked effect of rainfall on the bacteriological quality of water. Of a total of 44 water samples, 26 yielded virus in concentrations from 4 to 167 plaque-forming units per 100-gallon (ca. 378.5-liter) sample. Of a total of 40 pools of 10 to 12 oysters each, virus was found in 14 pools at a concentration of 6 to 224 plaque-forming units per 100 g of oyster meat. On five occasions, virus was found in water samples when no virus could be detected in oysters harvested from the same sites. This study indicates that current bacteriological standards for determining the safety of shellfish and shellfish-growing waters do no reflect the occurrence of enteroviruses."}
{"id": "PMID:222211", "title": "Survival of bacteria in carcasses.", "content": "Bacteria injected into the bloodstream of guinea pigs shortly before death decreased in number in carcass tissues for about 1 h after death. If initial bacterial numbers were sufficiently low, all bacteria were eliminated, and carcass tissues were sterile 24 h after death. Carcass tissue sterility was maintained with an initial density of Clostridium perfringens or Salmonella typhimurium of 20 cells per g or with an initial density of the other species examined of several hundred cells per gram. With larger numbers of strict and facultative anaerobes, growth commenced after 3 h in carcasses incubated at 30 degrees C. Spores of C. perfringens were killed over the same period as vegetative cells, but growth did not commence until 8 h after death. Bactericidal activity in carcass tissues must therefore be taken into account in evaluating the significance of reports of deep-tissue contamination of carcasses from meat animals.", "contents": "Survival of bacteria in carcasses. Bacteria injected into the bloodstream of guinea pigs shortly before death decreased in number in carcass tissues for about 1 h after death. If initial bacterial numbers were sufficiently low, all bacteria were eliminated, and carcass tissues were sterile 24 h after death. Carcass tissue sterility was maintained with an initial density of Clostridium perfringens or Salmonella typhimurium of 20 cells per g or with an initial density of the other species examined of several hundred cells per gram. With larger numbers of strict and facultative anaerobes, growth commenced after 3 h in carcasses incubated at 30 degrees C. Spores of C. perfringens were killed over the same period as vegetative cells, but growth did not commence until 8 h after death. Bactericidal activity in carcass tissues must therefore be taken into account in evaluating the significance of reports of deep-tissue contamination of carcasses from meat animals."}
{"id": "PMID:222218", "title": "Microscopically controlled surgery for extramammary Paget's disease.", "content": "In five cases of extramammary Paget's disease (EMPD), the neoplasms were removed under complete microscopical control by means of fixed-tissue chemosurgical technique in one case and fresh-tissue technique in four cases. In each lesion there were histologically involved areas extending several centimeters into clinically normal-appearing skin. All patients have been free of the disease for periods from four months to nine years. Other authors using conventional surgery have reported a recurrence rate of 44%. Microscopically controlled surgery offers the most reliable method of removing all of the neoplastic tissue EMPD and preserves as much normal tissue as possible.", "contents": "Microscopically controlled surgery for extramammary Paget's disease. In five cases of extramammary Paget's disease (EMPD), the neoplasms were removed under complete microscopical control by means of fixed-tissue chemosurgical technique in one case and fresh-tissue technique in four cases. In each lesion there were histologically involved areas extending several centimeters into clinically normal-appearing skin. All patients have been free of the disease for periods from four months to nine years. Other authors using conventional surgery have reported a recurrence rate of 44%. Microscopically controlled surgery offers the most reliable method of removing all of the neoplastic tissue EMPD and preserves as much normal tissue as possible."}
{"id": "PMID:222219", "title": "Seroepidemiology of cytomegalovirus infections during the first years of life in urban communities.", "content": "Using indirect haemagglutination assay, combined with a collection of blood samples on blotting cards, seroepidemiological surveys of cytomegalovirus infections during early infancy have been done in different populations (French and immigrant) in urban areas. The comparison of CMV antibody status of mothers and their children at 10 months and at 2 years of age enables possible factors of viral transmission to be defined. During the first year of life, seropositive mothers were the only source of infection and they remained the main source during the second year. Socioeconomic class and educational level are determinant factors in the incidence of viral transmission.", "contents": "Seroepidemiology of cytomegalovirus infections during the first years of life in urban communities. Using indirect haemagglutination assay, combined with a collection of blood samples on blotting cards, seroepidemiological surveys of cytomegalovirus infections during early infancy have been done in different populations (French and immigrant) in urban areas. The comparison of CMV antibody status of mothers and their children at 10 months and at 2 years of age enables possible factors of viral transmission to be defined. During the first year of life, seropositive mothers were the only source of infection and they remained the main source during the second year. Socioeconomic class and educational level are determinant factors in the incidence of viral transmission."}
{"id": "PMID:222220", "title": "The spread of Coxsackie B1 infection.", "content": "During June and July 1977 5 junior boys in a boarding school for 800 pupils became ill with a mild infection caused by Coxsackie B1. The school had been taking part in a vaccine trial, and paired blood samples had been taken from new entrants in October 1976 and October 1977. 18% of the boys susceptible to the infection developed antibodies. The results suggest that dormitories are more important than the day-to-day contacts in the spread of infection. The advisability of nursing children with known or suspected enterovirus infections in open wards in hospital is questioned.", "contents": "The spread of Coxsackie B1 infection. During June and July 1977 5 junior boys in a boarding school for 800 pupils became ill with a mild infection caused by Coxsackie B1. The school had been taking part in a vaccine trial, and paired blood samples had been taken from new entrants in October 1976 and October 1977. 18% of the boys susceptible to the infection developed antibodies. The results suggest that dormitories are more important than the day-to-day contacts in the spread of infection. The advisability of nursing children with known or suspected enterovirus infections in open wards in hospital is questioned."}
{"id": "PMID:222222", "title": "The surgical aspects of insulinomas.", "content": "The clinical diagnosis of insulinoma rests on the demonstration of Whipple's triad (symptoms of hypoglycimia, low circulating glucose and prompt relief of symptoms after glucose administration). Biochemically, the association of an increased value of immunoreactive insulin with a low glucose value is diagnostic of insulin-mediated hypoglycemia. Angiographic localization of these tumors is accomplished in more than 90% of cases. The pathologic changes are usually due to a single adenoma, for which surgical enucleation is the procedure of choice. Malignancy and persistent hypoglycemia occur in slightly less than 10% of cases and can be fairly successfully managed by diazoxide and streptozotocin.", "contents": "The surgical aspects of insulinomas. The clinical diagnosis of insulinoma rests on the demonstration of Whipple's triad (symptoms of hypoglycimia, low circulating glucose and prompt relief of symptoms after glucose administration). Biochemically, the association of an increased value of immunoreactive insulin with a low glucose value is diagnostic of insulin-mediated hypoglycemia. Angiographic localization of these tumors is accomplished in more than 90% of cases. The pathologic changes are usually due to a single adenoma, for which surgical enucleation is the procedure of choice. Malignancy and persistent hypoglycemia occur in slightly less than 10% of cases and can be fairly successfully managed by diazoxide and streptozotocin."}
{"id": "PMID:222223", "title": "Bronchioloalveolar cell carcinoma of the lung: a clinicopathological study.", "content": "Thirty-nine patients with bronchioloalveolar carcinoma were reviewed. The primary lung tumor from 27 patients was examined and divided by histological criteria into three categories. The type 1 pattern was associated with a mean survival of 4.7 years. A mean survival of 3.8 years was attained in patients with type 2. Patients with the type 3 pattern had an average survival of 1.4 years. There was a statistically significant difference in survival when types 1 and 2 together were compared with type 3 (rho less than 0.05). Another statistically significant finding was a mean survival of 5.2 years in patients with negative lymph nodes after surgical resection and a 2.2 year mean survival in patients with positive nodes. The tumor histology of bronchioloalveolar carcinoma should be examined carefully to obtain helpful information in predicting survival. We recommend that these tumors be classified as well-differentiated or poorly differentiated bronchioloalveolar carcinoma.", "contents": "Bronchioloalveolar cell carcinoma of the lung: a clinicopathological study. Thirty-nine patients with bronchioloalveolar carcinoma were reviewed. The primary lung tumor from 27 patients was examined and divided by histological criteria into three categories. The type 1 pattern was associated with a mean survival of 4.7 years. A mean survival of 3.8 years was attained in patients with type 2. Patients with the type 3 pattern had an average survival of 1.4 years. There was a statistically significant difference in survival when types 1 and 2 together were compared with type 3 (rho less than 0.05). Another statistically significant finding was a mean survival of 5.2 years in patients with negative lymph nodes after surgical resection and a 2.2 year mean survival in patients with positive nodes. The tumor histology of bronchioloalveolar carcinoma should be examined carefully to obtain helpful information in predicting survival. We recommend that these tumors be classified as well-differentiated or poorly differentiated bronchioloalveolar carcinoma."}
{"id": "PMID:222221", "title": "Subacute cadmium intoxication in jewelry workers: an evaluation of diagnostic procedures.", "content": "An outbreak of cadmium intoxication in a jewelry factory provided an opportunity for evaluating the usefulness of diagnostic procedures used to evaluate human cadmium toxicity. Blood cadmium levels in workers exposed to cadmium were higher (.93 micrograms/100ml vs .38 micrograms/100 ml) than in unexposed workers. A dose-response relationship was noted between blood cadmium level and symptom prevalence in four symptoms (dyspnea, chest pain, dysuria, and dizziness). Segmental hair analysis revealed highest cadmium levels (up to 19 micrograms/gm) in segments formed prior to cadmium exposure, suggesting that extrinsic contamination was the primary source of cadmium in the hair. beta2-microglobulin levels were within normal limits. No significant renal or pulmonary dysfunction was noted. Symptoms ceased after a cadmium-containing brazing alloy used in jewelry production was replaced, yet urine cadmium levels remained persistently elevated in four workers. Blood cadmium determinations were found to be useful in evaluating symptoms potentially related to cadmium intoxication.", "contents": "Subacute cadmium intoxication in jewelry workers: an evaluation of diagnostic procedures. An outbreak of cadmium intoxication in a jewelry factory provided an opportunity for evaluating the usefulness of diagnostic procedures used to evaluate human cadmium toxicity. Blood cadmium levels in workers exposed to cadmium were higher (.93 micrograms/100ml vs .38 micrograms/100 ml) than in unexposed workers. A dose-response relationship was noted between blood cadmium level and symptom prevalence in four symptoms (dyspnea, chest pain, dysuria, and dizziness). Segmental hair analysis revealed highest cadmium levels (up to 19 micrograms/gm) in segments formed prior to cadmium exposure, suggesting that extrinsic contamination was the primary source of cadmium in the hair. beta2-microglobulin levels were within normal limits. No significant renal or pulmonary dysfunction was noted. Symptoms ceased after a cadmium-containing brazing alloy used in jewelry production was replaced, yet urine cadmium levels remained persistently elevated in four workers. Blood cadmium determinations were found to be useful in evaluating symptoms potentially related to cadmium intoxication."}
{"id": "PMID:222226", "title": "[Stress and immunity in cattle].", "content": "Stress of variable length may be caused in calf by parenteral administration of supercortisol and application of acute thermal load. Hormonal or thermal stress may have negative impact on postvaccinal immunity to paratyphoid (Salmonella dublin 81), as may be interpreted with reference to the O-agglutination titre of blood serum. The extent to which immunity is suppressed by stress was found to depend on the moment of stress application, duration of stress, and age of the calf.", "contents": "[Stress and immunity in cattle]. Stress of variable length may be caused in calf by parenteral administration of supercortisol and application of acute thermal load. Hormonal or thermal stress may have negative impact on postvaccinal immunity to paratyphoid (Salmonella dublin 81), as may be interpreted with reference to the O-agglutination titre of blood serum. The extent to which immunity is suppressed by stress was found to depend on the moment of stress application, duration of stress, and age of the calf."}
{"id": "PMID:222228", "title": "Crystal-like deposits of amyloid in pancreatic islet cell tumors.", "content": "Numerous stellate crystal-like deposits of amyloid were observed in four human pancreatic islet cell tumors. Three of the tumors were associated with hypoglycemia or hyperinsulinemia, and the remaining one produced gastrin. Histochemical and ultrastructural studies confirmed the existence of amyloid in the deposits and also suggested the presence of adsorbed or incorporated mucopolysaccharides. Stellate amyloid deposits have previously been described in experimental systemic murine amyloidosis. The relationships of these stellate deposits to other forms of amyloid depostion are unknown.", "contents": "Crystal-like deposits of amyloid in pancreatic islet cell tumors. Numerous stellate crystal-like deposits of amyloid were observed in four human pancreatic islet cell tumors. Three of the tumors were associated with hypoglycemia or hyperinsulinemia, and the remaining one produced gastrin. Histochemical and ultrastructural studies confirmed the existence of amyloid in the deposits and also suggested the presence of adsorbed or incorporated mucopolysaccharides. Stellate amyloid deposits have previously been described in experimental systemic murine amyloidosis. The relationships of these stellate deposits to other forms of amyloid depostion are unknown."}
{"id": "PMID:222229", "title": "Lesions induced by encephalomyocarditis virus and coxsackievirus B in newborn mice.", "content": "Electron microscopic studies of various tissues from virus-infected newborn mice disclosed a consistent form of viral cytonecrotic ultrastructural lesion in divergent types of cells (myocardial, valvular fibroblastic, aortic, exocrine and endocrine pancreatic, and hepatic cells) due to three different picornaviruses (coxsackieviruses B4 and B1 and encephalomyocarditis virus). The lesion is characterized by numerous membrane-vesicle complexes, margination of nuclear chromatin or nuclear pyknosis, dilation of rough endoplasmic reticulum, inflammation, and, at times, mitochondrial swelling. It seems apparent that the finding of this ultrastructural type of cytonecrosis is characteristic of a picornaviral infection regardless of the tissue involved and the offending member of the picornavirus group.", "contents": "Lesions induced by encephalomyocarditis virus and coxsackievirus B in newborn mice. Electron microscopic studies of various tissues from virus-infected newborn mice disclosed a consistent form of viral cytonecrotic ultrastructural lesion in divergent types of cells (myocardial, valvular fibroblastic, aortic, exocrine and endocrine pancreatic, and hepatic cells) due to three different picornaviruses (coxsackieviruses B4 and B1 and encephalomyocarditis virus). The lesion is characterized by numerous membrane-vesicle complexes, margination of nuclear chromatin or nuclear pyknosis, dilation of rough endoplasmic reticulum, inflammation, and, at times, mitochondrial swelling. It seems apparent that the finding of this ultrastructural type of cytonecrosis is characteristic of a picornaviral infection regardless of the tissue involved and the offending member of the picornavirus group."}
{"id": "PMID:222230", "title": "Localized cytomegalovirus encephalitis contiguous to metastatic nasopharyngeal carcinoma.", "content": "We report a case of focal infection of the brain with cytomegalovirus (CMV) in a 14-year-old boy with metastatic lymphoepithelioma (nasopharyngeal carcinoma). Cytomegalovirus-bearing subependymal glia were only seen in the fourth ventricle, in close proximity to tumor cells, these were associated with an intense inflammatory cell exudate. The latter was due to enterococcal meningitis. There was no evidence of systemic CMV infection, and the typical encephalitis with glial nodules seen in acquired forms of the disease was lacking. We postulate that the infection gained access to the brain either with the tumor cells, which happened to carry CMV genome, or with virus-carrying polymorphonuclear leukocytes migrating to the bacterial meningitis. It is also possible that the proliferating subependymal glia were unduly susceptible to CMV when the host defense mechanisms were compromised.", "contents": "Localized cytomegalovirus encephalitis contiguous to metastatic nasopharyngeal carcinoma. We report a case of focal infection of the brain with cytomegalovirus (CMV) in a 14-year-old boy with metastatic lymphoepithelioma (nasopharyngeal carcinoma). Cytomegalovirus-bearing subependymal glia were only seen in the fourth ventricle, in close proximity to tumor cells, these were associated with an intense inflammatory cell exudate. The latter was due to enterococcal meningitis. There was no evidence of systemic CMV infection, and the typical encephalitis with glial nodules seen in acquired forms of the disease was lacking. We postulate that the infection gained access to the brain either with the tumor cells, which happened to carry CMV genome, or with virus-carrying polymorphonuclear leukocytes migrating to the bacterial meningitis. It is also possible that the proliferating subependymal glia were unduly susceptible to CMV when the host defense mechanisms were compromised."}
{"id": "PMID:222231", "title": "Dementia-Parkinsonism syndrome with numerous Lewy bodies and senile plaques in cerebral cortex.", "content": "Five cases of age range 62-72 years with progressive dementia and muscular rigidity are reported and discussed from the clinicopathologic point of view. The neuropathology of these cases was characterized by the widespread occurrence of Lewy bodies (LB) in the CNS as well as the presence of senile changes. The presence of numerous LB in the cerebral cortex and basal ganglia was especially characteristic, although their distribution pattern in the diencephalon and brain stem was identical to that found in paralysis agitans. On the other hand, the presence of senile changes in the cerebral cortex was almost identical to the neuropathology of senile dementia or Alzheimer's disease. Nosologically, the present cases may represent either a combination of atypical paralysis agitans with senile dementia and Alzheimer's disease, or a new disease.", "contents": "Dementia-Parkinsonism syndrome with numerous Lewy bodies and senile plaques in cerebral cortex. Five cases of age range 62-72 years with progressive dementia and muscular rigidity are reported and discussed from the clinicopathologic point of view. The neuropathology of these cases was characterized by the widespread occurrence of Lewy bodies (LB) in the CNS as well as the presence of senile changes. The presence of numerous LB in the cerebral cortex and basal ganglia was especially characteristic, although their distribution pattern in the diencephalon and brain stem was identical to that found in paralysis agitans. On the other hand, the presence of senile changes in the cerebral cortex was almost identical to the neuropathology of senile dementia or Alzheimer's disease. Nosologically, the present cases may represent either a combination of atypical paralysis agitans with senile dementia and Alzheimer's disease, or a new disease."}
{"id": "PMID:222232", "title": "Ductal carcinoma of the pancreas. Rationales for total pancreatectomy.", "content": "In order to evaluate total pancreatectomy as a surgical procedure for ductal carcinoma of the pancreas, a histopathological analysis was made on 18 resected specimens with special regard to the pattern of cancer growth in the pancreatic tissue. In five of them there was no lymphatic involvement or extrapancreatic invasion, but cancer extended continuously to the tail along with the pancreatic ducts and reached the end of the ducts in three cases. All 11 patients treated with Whipple's procedure died of recurrence, while of four total pancreatectomized patients, one with continuously invasive cancer to the end of the pancreatic duct has been living more than eight years postoperatively. We believe that total pancreatectomy for this type of \"intraductal spreading cancer\" without invasion beyond the pancreas is indicated as a radical procedure.", "contents": "Ductal carcinoma of the pancreas. Rationales for total pancreatectomy. In order to evaluate total pancreatectomy as a surgical procedure for ductal carcinoma of the pancreas, a histopathological analysis was made on 18 resected specimens with special regard to the pattern of cancer growth in the pancreatic tissue. In five of them there was no lymphatic involvement or extrapancreatic invasion, but cancer extended continuously to the tail along with the pancreatic ducts and reached the end of the ducts in three cases. All 11 patients treated with Whipple's procedure died of recurrence, while of four total pancreatectomized patients, one with continuously invasive cancer to the end of the pancreatic duct has been living more than eight years postoperatively. We believe that total pancreatectomy for this type of \"intraductal spreading cancer\" without invasion beyond the pancreas is indicated as a radical procedure."}
{"id": "PMID:222233", "title": "Cytomegalovirus infection of the colon associated with ulcerative colitis.", "content": "We report a 12th case in which infection of the colon with cytomegalovirus was demonstrated in association with ulcerative collitis. Rectal biopsy has proven to be reliable in identifying cells with cytomegaloviral inclusion bodies if careful histologic evaluation is performed. Thus far, prognosis has been serious when cytomegalovirus of the colon has been documented in ulcerative colitis. Nine of 12 patients have required a colectomy, and only seven of 12 have survived.", "contents": "Cytomegalovirus infection of the colon associated with ulcerative colitis. We report a 12th case in which infection of the colon with cytomegalovirus was demonstrated in association with ulcerative collitis. Rectal biopsy has proven to be reliable in identifying cells with cytomegaloviral inclusion bodies if careful histologic evaluation is performed. Thus far, prognosis has been serious when cytomegalovirus of the colon has been documented in ulcerative colitis. Nine of 12 patients have required a colectomy, and only seven of 12 have survived."}
{"id": "PMID:222235", "title": "Variation in susceptibility of HeLa cell lines to coxsackievirus A9.", "content": "In the course of serial passages for several years a line of uncloned HeLa cells (A line) showed a gradual decrease in plaquing efficiency by coxsackievirus A9 (CA9 virus), while subcultures prepared from the same line kept frozen at an early passage level (A original line) did not show any change. However, it was observed later that the plaque-forming ability of the A original line (A orig. line) also decreased after serial passages as was observed with the A line. Comparing the characteristics of the same cell line at two different passage levels, it was found that the efficiency of adsorption of virus to cells was nearly the same, while virus yield at 8 hours after infection was different. The activity of alkaline phosphatase of cells was also different between these two passage levels, suggesting that a high enzymatic activity is associated with the susceptibility of cell cultures to CA9 virus. Magnesium chloride at 25 mM enhanced plaque formation by CA9 virus in highly passaged less susceptible cell cultures, and a possible role of the chemical as a stabilizer of alkaline phosphatase was discussed.", "contents": "Variation in susceptibility of HeLa cell lines to coxsackievirus A9. In the course of serial passages for several years a line of uncloned HeLa cells (A line) showed a gradual decrease in plaquing efficiency by coxsackievirus A9 (CA9 virus), while subcultures prepared from the same line kept frozen at an early passage level (A original line) did not show any change. However, it was observed later that the plaque-forming ability of the A original line (A orig. line) also decreased after serial passages as was observed with the A line. Comparing the characteristics of the same cell line at two different passage levels, it was found that the efficiency of adsorption of virus to cells was nearly the same, while virus yield at 8 hours after infection was different. The activity of alkaline phosphatase of cells was also different between these two passage levels, suggesting that a high enzymatic activity is associated with the susceptibility of cell cultures to CA9 virus. Magnesium chloride at 25 mM enhanced plaque formation by CA9 virus in highly passaged less susceptible cell cultures, and a possible role of the chemical as a stabilizer of alkaline phosphatase was discussed."}
{"id": "PMID:222236", "title": "Fluorescence polarization of DPH-labeled cells adsorbing viruses and its diagnostic potential.", "content": "Mammalian or avian cells were labeled with a fluorescent probe DPH (1,6-diphenyl-1,3,5-hexatriene). Within a few minutes after adsorption of various naked and enveloped viruses, the degree of fluorescence polarization (P) of the DPH embedded in the adsorbing cells as measured at 37 degrees C, was reduced, a finding indicating a decrease in the microviscosity of the lipids in the cell membrane. This change of fluidity was proportional to the concentration of the adsorbing virus and could be abolished or inhibited by homologous specific antiviral sera, but not by heterologous sera. Potential use of fluorescence polarization tests is described for titration of virus concentration, as well as for serological identification of a virus.", "contents": "Fluorescence polarization of DPH-labeled cells adsorbing viruses and its diagnostic potential. Mammalian or avian cells were labeled with a fluorescent probe DPH (1,6-diphenyl-1,3,5-hexatriene). Within a few minutes after adsorption of various naked and enveloped viruses, the degree of fluorescence polarization (P) of the DPH embedded in the adsorbing cells as measured at 37 degrees C, was reduced, a finding indicating a decrease in the microviscosity of the lipids in the cell membrane. This change of fluidity was proportional to the concentration of the adsorbing virus and could be abolished or inhibited by homologous specific antiviral sera, but not by heterologous sera. Potential use of fluorescence polarization tests is described for titration of virus concentration, as well as for serological identification of a virus."}
{"id": "PMID:222237", "title": "Detection of Luck\u00e9 herpes virus antigens in infected frog pronephric cells.", "content": "A frog pronephric cell line, infected with herpes virus derived from Luck\u00e9 renal carcinomas of Rana pipiens was examined for the presence of Luck\u00e9 herpes virus antigens. Non-infected pronephric cells were controls. Antiserum to purified Luck\u00e9 tumor herpes virus was applied in blind tests to the normal and virus infected cells. Both cytoplasmic and nuclear fluorescence was found in the herpes virus infected cells after indirect immunofluorescence with the antiserum. Infected cells cultivated at the optimum growth temperature of 25 degrees C or maintained at 9 degrees C, a temperature inducive to herpes virus replication, showed equivalent fluorescence reactions. No fluorescence was found in the normal pronephric cell line. Examination of parallel herpes infected cells showed cytopathic effect in monolayers by light microscopy, and nuclear or cytoplasmic immunofluorescence. Electron microscopic examination revealed proviral elements in nuclei and sparsely scattered herpes virus coincident with cytoplasmic fluorescence.", "contents": "Detection of Luck\u00e9 herpes virus antigens in infected frog pronephric cells. A frog pronephric cell line, infected with herpes virus derived from Luck\u00e9 renal carcinomas of Rana pipiens was examined for the presence of Luck\u00e9 herpes virus antigens. Non-infected pronephric cells were controls. Antiserum to purified Luck\u00e9 tumor herpes virus was applied in blind tests to the normal and virus infected cells. Both cytoplasmic and nuclear fluorescence was found in the herpes virus infected cells after indirect immunofluorescence with the antiserum. Infected cells cultivated at the optimum growth temperature of 25 degrees C or maintained at 9 degrees C, a temperature inducive to herpes virus replication, showed equivalent fluorescence reactions. No fluorescence was found in the normal pronephric cell line. Examination of parallel herpes infected cells showed cytopathic effect in monolayers by light microscopy, and nuclear or cytoplasmic immunofluorescence. Electron microscopic examination revealed proviral elements in nuclei and sparsely scattered herpes virus coincident with cytoplasmic fluorescence."}
{"id": "PMID:222238", "title": "Monkey interferon: activity on human cells and chromatographic properties. Brief report.", "content": "Monkey interferon (MKIF) produced in monkey BSC-1 cells infected with Newcastle disease virus showed antiviral activity on human foreskin fibroblasts and RD114cells--a human line transformed by feline sarcoma virus. The titer of the monkey interferon in human cells was 10--30 fold greater than that found in several normal monkey (BSC-1, CV-1 or SV 40 transformed (C2, C6, T-22) monkey cell lines tested. Ten to fifteen-fold purification of MKIF without loss of activity could be achieved by chromatography on Phenyl-Sepharose CL-4B. Antiviral activity of MKIF was fully resistant to treatment with 1 per cent sodium dodecyl sulfate (SDS).", "contents": "Monkey interferon: activity on human cells and chromatographic properties. Brief report. Monkey interferon (MKIF) produced in monkey BSC-1 cells infected with Newcastle disease virus showed antiviral activity on human foreskin fibroblasts and RD114cells--a human line transformed by feline sarcoma virus. The titer of the monkey interferon in human cells was 10--30 fold greater than that found in several normal monkey (BSC-1, CV-1 or SV 40 transformed (C2, C6, T-22) monkey cell lines tested. Ten to fifteen-fold purification of MKIF without loss of activity could be achieved by chromatography on Phenyl-Sepharose CL-4B. Antiviral activity of MKIF was fully resistant to treatment with 1 per cent sodium dodecyl sulfate (SDS)."}
{"id": "PMID:222239", "title": "Human cytomegalovirus induced changes in rabbit cells. Brief report.", "content": "After infection with human cytomegalovirus, rabbit lung fibroblasts showed, during the four week period of the experiment, cytopathic changes and virus-specific antigens demonstrable by fluorescent antibody. Infectious virus could be recovered from the infected cells by co-cultivation with human lung fibroblasts.", "contents": "Human cytomegalovirus induced changes in rabbit cells. Brief report. After infection with human cytomegalovirus, rabbit lung fibroblasts showed, during the four week period of the experiment, cytopathic changes and virus-specific antigens demonstrable by fluorescent antibody. Infectious virus could be recovered from the infected cells by co-cultivation with human lung fibroblasts."}
{"id": "PMID:222240", "title": "Guinea pig cytomegalovirus: transplacental transmission. Brief report.", "content": "A well characterized strain of guinea pig cytomegalovirus (GPCMV) was used to infect pregnant guinea pigs during various periods of pregnancy. Transplacental transmission of virus with invasion of the fetus was observed, even in some mothers with preinoculation evidence of GPCMV antibody. Fetal infection occurred during the middle third of pregnancy and GPCMV was isolated from many fetal tissues although histologic evidence of infection was not noted. During the last third, abortion of the pregnancy occurred in some animals. This report demonstrates that GPCMV may invade the fetus producing a sublethal, possibly mild infection which may be very similar to the usual type of CMV infection observed in the human newborn.", "contents": "Guinea pig cytomegalovirus: transplacental transmission. Brief report. A well characterized strain of guinea pig cytomegalovirus (GPCMV) was used to infect pregnant guinea pigs during various periods of pregnancy. Transplacental transmission of virus with invasion of the fetus was observed, even in some mothers with preinoculation evidence of GPCMV antibody. Fetal infection occurred during the middle third of pregnancy and GPCMV was isolated from many fetal tissues although histologic evidence of infection was not noted. During the last third, abortion of the pregnancy occurred in some animals. This report demonstrates that GPCMV may invade the fetus producing a sublethal, possibly mild infection which may be very similar to the usual type of CMV infection observed in the human newborn."}
{"id": "PMID:222241", "title": "Antiviral activity of virus-like particles from Lentinus edodes (Shiitake). Brief report.", "content": "Interferon (IF) induction and antiviral activity by purified spherical (S) or filamentous (F) virus-like particles and S-derived RNA was studied. A single administration of S particles prior to virus challenge reduced significantly the mortality of mice infected with western equine encephalitis (WEE) virus.", "contents": "Antiviral activity of virus-like particles from Lentinus edodes (Shiitake). Brief report. Interferon (IF) induction and antiviral activity by purified spherical (S) or filamentous (F) virus-like particles and S-derived RNA was studied. A single administration of S particles prior to virus challenge reduced significantly the mortality of mice infected with western equine encephalitis (WEE) virus."}
{"id": "PMID:222242", "title": "Asymptomatic infection of mouse hepatitis virus in the rat. Brief report.", "content": "After intranasal inoculation of suckling rats mouse hepatitis virus multiplied mostly in the nasal epithelium; though there were no symptoms, antibodies were produced. Antibodies were also demonstrated in adult rats. These findings suggest that the rat may be a natural host for the virus.", "contents": "Asymptomatic infection of mouse hepatitis virus in the rat. Brief report. After intranasal inoculation of suckling rats mouse hepatitis virus multiplied mostly in the nasal epithelium; though there were no symptoms, antibodies were produced. Antibodies were also demonstrated in adult rats. These findings suggest that the rat may be a natural host for the virus."}
{"id": "PMID:222243", "title": "Detection of three polypeptides in preparations of bovine viral diarrhoea virus.", "content": "Radiolabelled bovine viral diarrhoea/mucosal disease virus (BVDV) strains NADL and Oregon C24V were purified by different steps. Following immunoprecipitation, electrophoresis in SDS-polyacrylamide gels revealed three BVDV structural polypeptides with molecular weights of 57 (VP1), 44 (VP2), and 34 (VP3) kd. The two larger BVDV polypeptides VP1 and VP2 were found to be glycosylated (gp57, gp44). The data obtained on BVDV structural proteins demonstrate common features with hog cholera virus and indicate a common grouping with the family Togaviridae.", "contents": "Detection of three polypeptides in preparations of bovine viral diarrhoea virus. Radiolabelled bovine viral diarrhoea/mucosal disease virus (BVDV) strains NADL and Oregon C24V were purified by different steps. Following immunoprecipitation, electrophoresis in SDS-polyacrylamide gels revealed three BVDV structural polypeptides with molecular weights of 57 (VP1), 44 (VP2), and 34 (VP3) kd. The two larger BVDV polypeptides VP1 and VP2 were found to be glycosylated (gp57, gp44). The data obtained on BVDV structural proteins demonstrate common features with hog cholera virus and indicate a common grouping with the family Togaviridae."}
{"id": "PMID:222244", "title": "Antibody-dependent cell-mediated cytotoxicity (ADCC) in Aujeszky's disease.", "content": "Antibody-dependent cell-mediated cytotoxicity (ADCC) was studied using as targets 51Cr-labelled Vero cells infected with the Bartha strain of Aujeszky's disease virus (ADV). Using hyperimmune anti-ADV serum to sensitize the targets, porcine leukocytes from dextran-sedimented blood were found to be efficient effector cells yielding maximal 51Cr release by 16 hours. Whilst complement-dependent cytotoxic antibody could be demonstrated no enhancement of ADCC by complement was found. The sera of pigs vaccinated i.m. with Bartha virus were titrated in ADCC using leukocytes as effector cells and the results compared with those obtained by virus neutralization. ADCC proved to be a much more sensitive technique and might, therefore, provide the basis for a reliable diagnostic test. Partially purified lymphocytes and polymorphonuclear leukocytes from blood and peritoneal exudates, and macrophages from exudates were found to mediate ADCC with hyperimmune serum, but differences were observed in the efficiency and timing of their cytotoxic effects.", "contents": "Antibody-dependent cell-mediated cytotoxicity (ADCC) in Aujeszky's disease. Antibody-dependent cell-mediated cytotoxicity (ADCC) was studied using as targets 51Cr-labelled Vero cells infected with the Bartha strain of Aujeszky's disease virus (ADV). Using hyperimmune anti-ADV serum to sensitize the targets, porcine leukocytes from dextran-sedimented blood were found to be efficient effector cells yielding maximal 51Cr release by 16 hours. Whilst complement-dependent cytotoxic antibody could be demonstrated no enhancement of ADCC by complement was found. The sera of pigs vaccinated i.m. with Bartha virus were titrated in ADCC using leukocytes as effector cells and the results compared with those obtained by virus neutralization. ADCC proved to be a much more sensitive technique and might, therefore, provide the basis for a reliable diagnostic test. Partially purified lymphocytes and polymorphonuclear leukocytes from blood and peritoneal exudates, and macrophages from exudates were found to mediate ADCC with hyperimmune serum, but differences were observed in the efficiency and timing of their cytotoxic effects."}
{"id": "PMID:222245", "title": "Viral nucleic acid synthesis in HSV infected neural cells.", "content": "HSV-1 replication and synthesis of viral DNA and RNA have been examined in gliomas of human (COX) and rat origin (C6) and in mouse neuroblastomas (D2). COX cells fully support HSV-1 replication and show patterns of viral DNA and RNA synthesis similar to those seen in continuous line cells. HSV-1 also grows to high titers in D2 cells but without concomitant high levels of viral DNA and RNA synthesis in the infected cells. Finally, HSV-1 established a persistent infection in C6 cells. Viral mRNA and DNA synthesis could not be detected in these cultures. At cycles of approximately 15--20 days, the persistently infected cultures exhibited massive CPE and relatively high production of infectious HSV.", "contents": "Viral nucleic acid synthesis in HSV infected neural cells. HSV-1 replication and synthesis of viral DNA and RNA have been examined in gliomas of human (COX) and rat origin (C6) and in mouse neuroblastomas (D2). COX cells fully support HSV-1 replication and show patterns of viral DNA and RNA synthesis similar to those seen in continuous line cells. HSV-1 also grows to high titers in D2 cells but without concomitant high levels of viral DNA and RNA synthesis in the infected cells. Finally, HSV-1 established a persistent infection in C6 cells. Viral mRNA and DNA synthesis could not be detected in these cultures. At cycles of approximately 15--20 days, the persistently infected cultures exhibited massive CPE and relatively high production of infectious HSV."}
{"id": "PMID:222247", "title": "[Lysosomal-cation test and the prospects of its use in pathomorphological and laboratory diagnostic practice].", "content": "A cytochemical lysosome-cation test is proposed as suitable for use in diagnostic laboratories. The test is based on the detection of cationic protein and determinations of the fate of phagocytized and extracellular bacteria in inflammation foci. A method for simultaneous cytochemical detection of myeloperoxidase and cationic proteins in neutrophilic and eosinophilic granulocytes was developed. Using this method, a previously unknown variety of lysosomal granules devoid of peroxidase was detected in neutrophilic promyelocytes. The lysosomal cation test was shown to be useful for improved morphological diagnosis of leukemias, for the determination of the fate of phagocytized and non-phagocytized bacteria in inflammation foci, and of the level of nonspecific and infection resistance of the host.", "contents": "[Lysosomal-cation test and the prospects of its use in pathomorphological and laboratory diagnostic practice]. A cytochemical lysosome-cation test is proposed as suitable for use in diagnostic laboratories. The test is based on the detection of cationic protein and determinations of the fate of phagocytized and extracellular bacteria in inflammation foci. A method for simultaneous cytochemical detection of myeloperoxidase and cationic proteins in neutrophilic and eosinophilic granulocytes was developed. Using this method, a previously unknown variety of lysosomal granules devoid of peroxidase was detected in neutrophilic promyelocytes. The lysosomal cation test was shown to be useful for improved morphological diagnosis of leukemias, for the determination of the fate of phagocytized and non-phagocytized bacteria in inflammation foci, and of the level of nonspecific and infection resistance of the host."}
{"id": "PMID:222248", "title": "Adenoviral meningoencephalitis in a patient with lead toxicity.", "content": "Adenovirus type 12 was recovered from the CSF of a 36-year-old woman with adenoviral meningoencephalitis and lead toxicity. The serum level of lead was 199 micrograms/dL and the CSF level was 7 micrograms/dL. After therapy with edetate disodium calcium (Calcium Disodium Versenate), she had an uneventful recovery. The possibility of exacerbation of lead poisoning with encephalopathy due to adenovirus type 12 meningoencephalitis is raised.", "contents": "Adenoviral meningoencephalitis in a patient with lead toxicity. Adenovirus type 12 was recovered from the CSF of a 36-year-old woman with adenoviral meningoencephalitis and lead toxicity. The serum level of lead was 199 micrograms/dL and the CSF level was 7 micrograms/dL. After therapy with edetate disodium calcium (Calcium Disodium Versenate), she had an uneventful recovery. The possibility of exacerbation of lead poisoning with encephalopathy due to adenovirus type 12 meningoencephalitis is raised."}
{"id": "PMID:222251", "title": "Viral hepatitis and intrahepatic cholestasis of pregnancy.", "content": "Specific serological tests which are now available for the diagnosis of infection with hepatitis A and hepatitis B viruses, were used to distinguish viral hepatitis from other causes of liver disease in pregnancy. Forty-nine (51.6%) of 95 pregnant patients had viral hepatitis, 24 hepatitis A and 25 hepatitis B. The majority of patients (26 of 28) presenting before 22 weeks gestation had viral hepatitis. By contrast, 23 (34.3%) of the remaining 67 patients presenting with abnormal liver function tests at greater than or equal to 22 weeks gestation, had viral hepatitis; the majority of the remainder had features compatible with intrahepatic cholestasis of pregnancy. Although there were significant clinical and biochemical differences between the two groups, accurate diagnosis was only possible by using specific virological tests.", "contents": "Viral hepatitis and intrahepatic cholestasis of pregnancy. Specific serological tests which are now available for the diagnosis of infection with hepatitis A and hepatitis B viruses, were used to distinguish viral hepatitis from other causes of liver disease in pregnancy. Forty-nine (51.6%) of 95 pregnant patients had viral hepatitis, 24 hepatitis A and 25 hepatitis B. The majority of patients (26 of 28) presenting before 22 weeks gestation had viral hepatitis. By contrast, 23 (34.3%) of the remaining 67 patients presenting with abnormal liver function tests at greater than or equal to 22 weeks gestation, had viral hepatitis; the majority of the remainder had features compatible with intrahepatic cholestasis of pregnancy. Although there were significant clinical and biochemical differences between the two groups, accurate diagnosis was only possible by using specific virological tests."}
{"id": "PMID:222252", "title": "High density and low density lipoproteins in chronic renal failure before and after renal transplantation.", "content": "The hyperlipoproteinaemia accompanying chronic renal failure and renal transplantation has been re-examined in terms of the apoprotein (apo A and apo B) moieties of the high density (HDL) and low density (LDL) lipoproteins. Hypertriglyceridaemia is prevalent in chronic uraemia and is not corrected by haemodialysis or renal transplantation. Hypercholesterolaemia is characteristic only of renal allograft recipients. Apo A levels are reduced in undialyzed uraemic and remain low during haemodialysis, as well as in patients with renal allografts of less than six months duration. In renal transplant recipients of greater than one year duration, apo A levels are normalized. The normalization of apo A level is related to the stability of graft function, as determined by sequential analysis of 15 renal transplant recipients. Apo B levels are normal transplant recipients. Apo B levels are normal in uraemic and dialyzed patients, but are elevated in long term transplant recipients. Unlike apo A levels, this alteration does not appear to reflect the restoration of kidney function.", "contents": "High density and low density lipoproteins in chronic renal failure before and after renal transplantation. The hyperlipoproteinaemia accompanying chronic renal failure and renal transplantation has been re-examined in terms of the apoprotein (apo A and apo B) moieties of the high density (HDL) and low density (LDL) lipoproteins. Hypertriglyceridaemia is prevalent in chronic uraemia and is not corrected by haemodialysis or renal transplantation. Hypercholesterolaemia is characteristic only of renal allograft recipients. Apo A levels are reduced in undialyzed uraemic and remain low during haemodialysis, as well as in patients with renal allografts of less than six months duration. In renal transplant recipients of greater than one year duration, apo A levels are normalized. The normalization of apo A level is related to the stability of graft function, as determined by sequential analysis of 15 renal transplant recipients. Apo B levels are normal transplant recipients. Apo B levels are normal in uraemic and dialyzed patients, but are elevated in long term transplant recipients. Unlike apo A levels, this alteration does not appear to reflect the restoration of kidney function."}
{"id": "PMID:222255", "title": "Establishment of rat pancreatic endocrine cell lines by infection with simian virus 40.", "content": "The feasibility of infection and transformation by SV40 (simian virus 40) of primary cell cultures derived from newborn-rat pancreas was investigated. As judged by the presence of intranuclear SV40 T-antigen, exposure to the virus resulted specifically in infection and transformation of epithelioid (predominantly endocrine) cells. The transformed cells were subcultured (more than 64 passages) and cloned. Culture medium and acid/ethanol extracts of the cells did not contain detectable amounts of immunoreactive insulin after the third subculture. However, inoculation of such SV40-transformed pancreatic cells into immunodeficient rats results in tumours in which insulin production was partially restored through the passage in vivo, since the tumour cells contained and synthesized small amounts of immunoreactive insulin which co-migrated with an insulin marker on gel chromatography. Interestingly, the transformed cells maintained under tissue-culture conditions produced a protein immunologically related to insulin, soluble in aqueous buffer but insoluble in acid/ethanol. This 3000-dalton protein is too large to be a translation product of the rat preproinsulin 9S mRNA. SV40-transformed pancreatic cells might prove useful in the investigation of the factors controlling and maintaining insulin biosynthesis.", "contents": "Establishment of rat pancreatic endocrine cell lines by infection with simian virus 40. The feasibility of infection and transformation by SV40 (simian virus 40) of primary cell cultures derived from newborn-rat pancreas was investigated. As judged by the presence of intranuclear SV40 T-antigen, exposure to the virus resulted specifically in infection and transformation of epithelioid (predominantly endocrine) cells. The transformed cells were subcultured (more than 64 passages) and cloned. Culture medium and acid/ethanol extracts of the cells did not contain detectable amounts of immunoreactive insulin after the third subculture. However, inoculation of such SV40-transformed pancreatic cells into immunodeficient rats results in tumours in which insulin production was partially restored through the passage in vivo, since the tumour cells contained and synthesized small amounts of immunoreactive insulin which co-migrated with an insulin marker on gel chromatography. Interestingly, the transformed cells maintained under tissue-culture conditions produced a protein immunologically related to insulin, soluble in aqueous buffer but insoluble in acid/ethanol. This 3000-dalton protein is too large to be a translation product of the rat preproinsulin 9S mRNA. SV40-transformed pancreatic cells might prove useful in the investigation of the factors controlling and maintaining insulin biosynthesis."}
{"id": "PMID:222256", "title": "The turnover of cytochrome c in different skeletal-muscle fibre types of the rat.", "content": "The turnover of cytochrome c was determined in the three skeletal-muscle fibre types of adult male rats by a kinetic analysis that followed the time course of cytochrome c content change. Confirming evidence was obtained with double-labelling studies using delta-aminolaevulinate. Cytochrome c turnover was most rapid in the low-oxidative fast-twitch white fibre [t1/2 (half-life) about 4 days], slowest in the high-oxidative fast-twitch red fibre (t1/2 9-10 days) and relatively rapid in the high-oxidative slow-twitch red fibre (t1/2 5-6 days). Thus cytochrome c turnover does not strictly conform to either the appearance (i.e. red or white) or the contractile characteristics (i.e. fast or slow) of the muscle fibres. The synthesis rates needed to maintain the corresponding cytochrome c concentrations, however, were similarly high in the two mitochondria-rich red fibre types. These data illustrate that both the synthesis and degradation processes are important in establishing the cytochrome c concentrations that distinguish the different skeletal-muscle fibre types.", "contents": "The turnover of cytochrome c in different skeletal-muscle fibre types of the rat. The turnover of cytochrome c was determined in the three skeletal-muscle fibre types of adult male rats by a kinetic analysis that followed the time course of cytochrome c content change. Confirming evidence was obtained with double-labelling studies using delta-aminolaevulinate. Cytochrome c turnover was most rapid in the low-oxidative fast-twitch white fibre [t1/2 (half-life) about 4 days], slowest in the high-oxidative fast-twitch red fibre (t1/2 9-10 days) and relatively rapid in the high-oxidative slow-twitch red fibre (t1/2 5-6 days). Thus cytochrome c turnover does not strictly conform to either the appearance (i.e. red or white) or the contractile characteristics (i.e. fast or slow) of the muscle fibres. The synthesis rates needed to maintain the corresponding cytochrome c concentrations, however, were similarly high in the two mitochondria-rich red fibre types. These data illustrate that both the synthesis and degradation processes are important in establishing the cytochrome c concentrations that distinguish the different skeletal-muscle fibre types."}
{"id": "PMID:222298", "title": "Clearance of calcium pyrophosphate dihydrate crystals in vivo. I. Studies using 169Yb labeled triclinic crystals.", "content": "Synthetic triclinic calcium pyrophosphate dihydrate crystals were uniformly trace-labeled with Ytterbium-169 (169Yb), a pure gamma-emitting isotope with a halflife of 31 days. The solubility of the labeled crystals was similar to that of cold synthetic crystals. The clearance rate of labeled sterile crystals, sieved to obtain the desired size, was determined after injection of microgram quantities into 4 arthritic huuman and 3 normal adult rabbit joints and corrected by the observed rate of clearance of free 169Yb. The derived rate constants were then used to calculate the time required for half of the injected dose of CPPD to be cleared from the joint. Crystal clearance was found in all instances. Crystal removal from normal rabbit joints was much more rapid than from the much larger human arthritic joints and was inversely proportional to the size of the crystals injected.", "contents": "Clearance of calcium pyrophosphate dihydrate crystals in vivo. I. Studies using 169Yb labeled triclinic crystals. Synthetic triclinic calcium pyrophosphate dihydrate crystals were uniformly trace-labeled with Ytterbium-169 (169Yb), a pure gamma-emitting isotope with a halflife of 31 days. The solubility of the labeled crystals was similar to that of cold synthetic crystals. The clearance rate of labeled sterile crystals, sieved to obtain the desired size, was determined after injection of microgram quantities into 4 arthritic huuman and 3 normal adult rabbit joints and corrected by the observed rate of clearance of free 169Yb. The derived rate constants were then used to calculate the time required for half of the injected dose of CPPD to be cleared from the joint. Crystal clearance was found in all instances. Crystal removal from normal rabbit joints was much more rapid than from the much larger human arthritic joints and was inversely proportional to the size of the crystals injected."}
{"id": "PMID:222300", "title": "Chemotactic factor-induced generation of superoxide radicals by human neutrophils: effect of metabolic inhibitors and antiinflammatory drugs.", "content": "Human peripheral neutrophils generated superoxide radicals as assessed by ferricytochrome C reduction in response to activation by the synthetic chemotactic factor, N-formyl-methionyl-leucyl-phenylalanine. Superoxide generation was inhibited by 2-deoxy-D-glucose (ID50 4 X 10(-5)M), 2-iodoacetate (ID50 5 X 10(-5)M), and N-ethyl-maleimide (ID50 5 X 10(-6)M), suggesting a dependence on anaerobic glycolysis and sulfhydryl groups. Ouabain, microtubule-disrupting agents, inhibitors of respiration, oxidative phosphorylation, and protein and nucleic acid synthesis were without appreciable effects. Indomethacin (ID50 1 X 10(-4)M), ibuprofen (ID50 9 X 10(-4)M, and phenylbutazone (ID50 1 X 10(-5)M) all caused dose-dependent inhibition of superoxide generation at concentrations approximating those plasma and tissue levels obtained in human beings at therapeutic doses. Acetylsalicylic acid (125-500) microgram/ml) and aurothioglucose (10(-3)-10(-6)M) were without appreciable effects. Superoxide generation was inhibited only by relatively high concentrations of hydrocortisone (ID50 greater than 10(-3)M). Because superoxide radicals have been implicated in the pathogenesis of tissue injury in several forms of inflammation and arthritis in vivo, these studies suggest that the production of a potential cytotoxic factor may be subject to pharmacologic manipulation and that at least some of the antiphlogistic effects of the nonsteroidal antiinflammatory agents may be mediated through effects on superoxide production.", "contents": "Chemotactic factor-induced generation of superoxide radicals by human neutrophils: effect of metabolic inhibitors and antiinflammatory drugs. Human peripheral neutrophils generated superoxide radicals as assessed by ferricytochrome C reduction in response to activation by the synthetic chemotactic factor, N-formyl-methionyl-leucyl-phenylalanine. Superoxide generation was inhibited by 2-deoxy-D-glucose (ID50 4 X 10(-5)M), 2-iodoacetate (ID50 5 X 10(-5)M), and N-ethyl-maleimide (ID50 5 X 10(-6)M), suggesting a dependence on anaerobic glycolysis and sulfhydryl groups. Ouabain, microtubule-disrupting agents, inhibitors of respiration, oxidative phosphorylation, and protein and nucleic acid synthesis were without appreciable effects. Indomethacin (ID50 1 X 10(-4)M), ibuprofen (ID50 9 X 10(-4)M, and phenylbutazone (ID50 1 X 10(-5)M) all caused dose-dependent inhibition of superoxide generation at concentrations approximating those plasma and tissue levels obtained in human beings at therapeutic doses. Acetylsalicylic acid (125-500) microgram/ml) and aurothioglucose (10(-3)-10(-6)M) were without appreciable effects. Superoxide generation was inhibited only by relatively high concentrations of hydrocortisone (ID50 greater than 10(-3)M). Because superoxide radicals have been implicated in the pathogenesis of tissue injury in several forms of inflammation and arthritis in vivo, these studies suggest that the production of a potential cytotoxic factor may be subject to pharmacologic manipulation and that at least some of the antiphlogistic effects of the nonsteroidal antiinflammatory agents may be mediated through effects on superoxide production."}
{"id": "PMID:222301", "title": "Plasma lipoproteins and coronary arteriography in subjects in the program on the surgical control of the hyperlipidemias. Preliminary report.", "content": "Coronary arteriographic findings, plasma lipid and lipoprotein levels, and cigarette smoking history are reported for the first 101 male post myocardial infarction survivors who have been entered into the POSCH clinical trial. Estimates of the extent of stenosis in the major coronary arteries were made using 4 models ranging from a simple determination of the number of the 3 major vessels having significant (i.e. 50% or greater stenosis) disease to more complex methods of determining overall extent of disease in 14 major segments of the coronary arteries. Age was shown to be an important factor in the extent of vessel disease. When controlling for age, plasma cholesterol and LDL-cholesterol levels were shown to be related to the extent of disease, especially in Type II hyperlipoproteinemia subjects. Multiple linear regression analysis demonstrated that age and LDL-cholesterol had positive associations and HDL-cholesterol had an inverse association with the coronary artery  disease indices. In this comparatively \"healthy\" subgroup of the overall population of first MI survivors the major CHD risk factors are limited to plasma lipids and cigarette smoking.  This preliminary report of 10% of the recruitment objective of the project supports the currently held views of the lipid--atherosclerosis hypothesis regarding the effects of age-total plasma cholesterol, LDL--cholesterol, and HDL--cholesterol on the extent of coronary atherosclerotic plaques, as determined by coronary arteriography.", "contents": "Plasma lipoproteins and coronary arteriography in subjects in the program on the surgical control of the hyperlipidemias. Preliminary report. Coronary arteriographic findings, plasma lipid and lipoprotein levels, and cigarette smoking history are reported for the first 101 male post myocardial infarction survivors who have been entered into the POSCH clinical trial. Estimates of the extent of stenosis in the major coronary arteries were made using 4 models ranging from a simple determination of the number of the 3 major vessels having significant (i.e. 50% or greater stenosis) disease to more complex methods of determining overall extent of disease in 14 major segments of the coronary arteries. Age was shown to be an important factor in the extent of vessel disease. When controlling for age, plasma cholesterol and LDL-cholesterol levels were shown to be related to the extent of disease, especially in Type II hyperlipoproteinemia subjects. Multiple linear regression analysis demonstrated that age and LDL-cholesterol had positive associations and HDL-cholesterol had an inverse association with the coronary artery  disease indices. In this comparatively \"healthy\" subgroup of the overall population of first MI survivors the major CHD risk factors are limited to plasma lipids and cigarette smoking.  This preliminary report of 10% of the recruitment objective of the project supports the currently held views of the lipid--atherosclerosis hypothesis regarding the effects of age-total plasma cholesterol, LDL--cholesterol, and HDL--cholesterol on the extent of coronary atherosclerotic plaques, as determined by coronary arteriography."}
{"id": "PMID:222302", "title": "Lipid--lipoprotein composition in hypercholesterolemic children and their parents.", "content": "In 13 hypercholesterolemic children, re-screened for serum cholesterol after a 1-year interval, hypercholesterolemia was confirmed in only 61.5% of the cases. A tentative explanation seems to be the statistical principle of regression towards the mean. The lipid--lipoprotein analysis showed that serum and LDL cholesterol concentrations in the 13 hypercholesterolemic children and their parents were significantly higher compared to controls (children and parents). At re-screening, hyper-LDL cholesterolemia was present in only 8 of the 13 children (61.5%); 4 cases exhibited hyper-HDL cholesterolemia (30.7%). The high prevalence of the parents repeating the lipoprotein abnormality and the electrophoretic pattern found in the propositi (children) confirms the familial aggregation of the hypercholesterolemic states (hyper-LDL and hyper-HDL cholesterolemia). In conclusion the results of our study stress the importance of determining the lipid--lipoprotein composition, rather then merely evaluating total serum cholesterol in order to make a correct diagnosis of the hypercholesterolemic state. It should also be emphasized that the lipoprotein disturbances and their familial aggregation may be detected early in childhood, suggesting that the familial screening for risk factors of atherosclerosis should be done at pediatric age.", "contents": "Lipid--lipoprotein composition in hypercholesterolemic children and their parents. In 13 hypercholesterolemic children, re-screened for serum cholesterol after a 1-year interval, hypercholesterolemia was confirmed in only 61.5% of the cases. A tentative explanation seems to be the statistical principle of regression towards the mean. The lipid--lipoprotein analysis showed that serum and LDL cholesterol concentrations in the 13 hypercholesterolemic children and their parents were significantly higher compared to controls (children and parents). At re-screening, hyper-LDL cholesterolemia was present in only 8 of the 13 children (61.5%); 4 cases exhibited hyper-HDL cholesterolemia (30.7%). The high prevalence of the parents repeating the lipoprotein abnormality and the electrophoretic pattern found in the propositi (children) confirms the familial aggregation of the hypercholesterolemic states (hyper-LDL and hyper-HDL cholesterolemia). In conclusion the results of our study stress the importance of determining the lipid--lipoprotein composition, rather then merely evaluating total serum cholesterol in order to make a correct diagnosis of the hypercholesterolemic state. It should also be emphasized that the lipoprotein disturbances and their familial aggregation may be detected early in childhood, suggesting that the familial screening for risk factors of atherosclerosis should be done at pediatric age."}
{"id": "PMID:222303", "title": "Influence of oral polyunsaturated and saturated phospholipid treatment on the lipid composition and fatty acid profile of chimpanzee lipoproteins.", "content": "The influence of treatment with polyunsaturated lecithin (EPL) and with saturated lecithin on the lipoprotein composition and fatty acid profile was investigated in 4 male chimpanzees. The animals were successively given 3 isocaloric diets containing the same amount of fat with a degree of saturation varying from 1 in the control diet to 0.2 in the diet enriched with polyunsaturated lecithin, to 4 in the diet enrich with saturated lecithin. The VLDL, LDL and HDL3 fractions were isolated by ultracentrifugal flotation; changes in their lipid and fatty acid composition were followed and their microviscosity was measured. The treatment with polyunsaturated lecithin increases the cholesterol esters and lysolecithin content in HDL3, presumably via activation of the enzyme LCAT. These modified HDL particles have a more fluid surface and a denser core and are susceptible to act as better cholesterol carriers. A complementary effect of this treatment is a decrease of the plasma triglycerides and VLDL concentration, an increase in the unsaturation ratio of the triglycerides which might take place via activation of triglyceride lipase. The saturated lecithin treatment increases the plasma VLDL and LDL concentrations and the triglyceride levels and increases mostly the saturation ratio of the cholesterol esters. These effects are likely to enhance the progression of atherosclerosis.", "contents": "Influence of oral polyunsaturated and saturated phospholipid treatment on the lipid composition and fatty acid profile of chimpanzee lipoproteins. The influence of treatment with polyunsaturated lecithin (EPL) and with saturated lecithin on the lipoprotein composition and fatty acid profile was investigated in 4 male chimpanzees. The animals were successively given 3 isocaloric diets containing the same amount of fat with a degree of saturation varying from 1 in the control diet to 0.2 in the diet enriched with polyunsaturated lecithin, to 4 in the diet enrich with saturated lecithin. The VLDL, LDL and HDL3 fractions were isolated by ultracentrifugal flotation; changes in their lipid and fatty acid composition were followed and their microviscosity was measured. The treatment with polyunsaturated lecithin increases the cholesterol esters and lysolecithin content in HDL3, presumably via activation of the enzyme LCAT. These modified HDL particles have a more fluid surface and a denser core and are susceptible to act as better cholesterol carriers. A complementary effect of this treatment is a decrease of the plasma triglycerides and VLDL concentration, an increase in the unsaturation ratio of the triglycerides which might take place via activation of triglyceride lipase. The saturated lecithin treatment increases the plasma VLDL and LDL concentrations and the triglyceride levels and increases mostly the saturation ratio of the cholesterol esters. These effects are likely to enhance the progression of atherosclerosis."}
{"id": "PMID:222304", "title": "Accumulation and loss of cholesterol esters in monkey arterial smooth muscle cells exposed to normal and hyperlipemic serum lipoproteins.", "content": "The effects of high low and very low density lipoprotein fractions from normal or hyperlipemic rhesus monkey serum on the accumulation or removal of cholesterol esters from rhesus monkey smooth muscle cells in tissue culture were determined. Serum or serum lipoproteins were labeled with [14C] free cholesterol and adjusted to the same free cholesterol level in the incubation medium. Of the two normal lipoproteins examined, the LDL fraction caused more esterification than the HDL. Cells incubated in hyperlipemic serum showed a 2-fold stimulation in esterification as compared to cells in normal serum. This was contributed by hyperlipemic VLDL and LDL and led to a concomitant increase in cellular cholesterol ester content. Both hyperlipemic LDL and HDL stimulated esterification when compared to their normal counterparts. Cholesterol ester removal was examined by incubating the serum or lipoprotein fractions with cells enriched in cholesterol ester through a prior exposure to hyperlipemic serum. The cells incubated in normal or hyperlipemic HDL or lipoprotein-deficient serum had the lowest cholesterol ester content. Thus, the lipoprotein fractions which caused the lowest levels of cholesterol esterification were also the most efficient in the removal of cellular cholesterol esters.", "contents": "Accumulation and loss of cholesterol esters in monkey arterial smooth muscle cells exposed to normal and hyperlipemic serum lipoproteins. The effects of high low and very low density lipoprotein fractions from normal or hyperlipemic rhesus monkey serum on the accumulation or removal of cholesterol esters from rhesus monkey smooth muscle cells in tissue culture were determined. Serum or serum lipoproteins were labeled with [14C] free cholesterol and adjusted to the same free cholesterol level in the incubation medium. Of the two normal lipoproteins examined, the LDL fraction caused more esterification than the HDL. Cells incubated in hyperlipemic serum showed a 2-fold stimulation in esterification as compared to cells in normal serum. This was contributed by hyperlipemic VLDL and LDL and led to a concomitant increase in cellular cholesterol ester content. Both hyperlipemic LDL and HDL stimulated esterification when compared to their normal counterparts. Cholesterol ester removal was examined by incubating the serum or lipoprotein fractions with cells enriched in cholesterol ester through a prior exposure to hyperlipemic serum. The cells incubated in normal or hyperlipemic HDL or lipoprotein-deficient serum had the lowest cholesterol ester content. Thus, the lipoprotein fractions which caused the lowest levels of cholesterol esterification were also the most efficient in the removal of cellular cholesterol esters."}
{"id": "PMID:222305", "title": "Decreased high density lipoprotein-cholesterol levels in male patients with transient ischemic attacks.", "content": "Plasma lipid and lipoproteins levels were determined in a continuous series of 50 patients (36 males and 14 females), mean age around 50 years, with a clinical diagnosis of transient ischemic attacks (TIAs). TIA was defined as a sudden episode of focal cerebrovascular insufficiency, with complete resolution of the symptoms within 24 h. TIAs are considered an important prognostic symptom for ischemic cerebrovascular diseases, being manifest in approximately 45% of the patients later undergoing a complete stroke. Plasma total cholesterol levels did not differ in these patients, when compared with a similar series of patients of the same age and sex, free of cerebrovascular lesions. A slight elevation of mean triglyceride levels was detected in the patients of both sexes, as well as higher incidence of type IV hyperlipoproteinemia. The most significant finding, however, observed only in male TIA patients, was that of significantly reduced high density lipoprotein (HDL)-cholesterol levels. This reduction (-19.7% compared to the control group) is similar to that recently reported for patients with clear-cut ischemic cerebrovascular disease. The detection of decreased HDL-cholesterol levels in male TIA patients may be of considerable significance for a prognostic evaluation of this biochemical parameter.", "contents": "Decreased high density lipoprotein-cholesterol levels in male patients with transient ischemic attacks. Plasma lipid and lipoproteins levels were determined in a continuous series of 50 patients (36 males and 14 females), mean age around 50 years, with a clinical diagnosis of transient ischemic attacks (TIAs). TIA was defined as a sudden episode of focal cerebrovascular insufficiency, with complete resolution of the symptoms within 24 h. TIAs are considered an important prognostic symptom for ischemic cerebrovascular diseases, being manifest in approximately 45% of the patients later undergoing a complete stroke. Plasma total cholesterol levels did not differ in these patients, when compared with a similar series of patients of the same age and sex, free of cerebrovascular lesions. A slight elevation of mean triglyceride levels was detected in the patients of both sexes, as well as higher incidence of type IV hyperlipoproteinemia. The most significant finding, however, observed only in male TIA patients, was that of significantly reduced high density lipoprotein (HDL)-cholesterol levels. This reduction (-19.7% compared to the control group) is similar to that recently reported for patients with clear-cut ischemic cerebrovascular disease. The detection of decreased HDL-cholesterol levels in male TIA patients may be of considerable significance for a prognostic evaluation of this biochemical parameter."}
{"id": "PMID:222307", "title": "Body composition in hypopituitary dwarfs before and during human growth hormone therapy.", "content": "The clinical characteristics and body composition of eight hypopituitary dwarfs (10.2-21.6 yr) were analyzed before and after 6 and 12 mo of growth hormone therapy. 2 IU 3 times/wk. Before treatment, growth rate was 1.8 +/- 0.7 cm/yr, height age was 2.0-12.8 yr less, and bone age 2.0-11.1 yr less than chronologic age. Total body water (TBW), lean body mass (LBM), extracellular water (ECW), and intracellular water (ICW) were below normal for chronologic age, but normal for height. Muscle mass (MM) was below normal for age and height. During HGH therapy, growth rate was 7.1 +/- 1.6 cm/yr in the first 6 mo and 7.8 +/- 1.4 cm/yr during the next 6 mo; the ratio of change in height age to change in chronologic age was greater than or equal to 1.0 in all patients and the ratio of change in bone age to change in height age was 1.2 in one patient and less than or equal to 1.0 in the others. TBW, LBM, ECW, and ICW increased according to height increments; however, MM increased at a faster rate than expected from the height gains. Also, a relative or absolute loss of total body fat was recorded during the first 6 mo of therapy. It is suggested (1) that among the body composition parameters studied, muscle mass is the tissue most closely reflecting the lack of HGH and also its therapeutic benefits and (2) evaluation of body composition in hypopituitary dwarfs in response to HGH therapy shows striking changes not reflected by the determination of stature or weight alone.", "contents": "Body composition in hypopituitary dwarfs before and during human growth hormone therapy. The clinical characteristics and body composition of eight hypopituitary dwarfs (10.2-21.6 yr) were analyzed before and after 6 and 12 mo of growth hormone therapy. 2 IU 3 times/wk. Before treatment, growth rate was 1.8 +/- 0.7 cm/yr, height age was 2.0-12.8 yr less, and bone age 2.0-11.1 yr less than chronologic age. Total body water (TBW), lean body mass (LBM), extracellular water (ECW), and intracellular water (ICW) were below normal for chronologic age, but normal for height. Muscle mass (MM) was below normal for age and height. During HGH therapy, growth rate was 7.1 +/- 1.6 cm/yr in the first 6 mo and 7.8 +/- 1.4 cm/yr during the next 6 mo; the ratio of change in height age to change in chronologic age was greater than or equal to 1.0 in all patients and the ratio of change in bone age to change in height age was 1.2 in one patient and less than or equal to 1.0 in the others. TBW, LBM, ECW, and ICW increased according to height increments; however, MM increased at a faster rate than expected from the height gains. Also, a relative or absolute loss of total body fat was recorded during the first 6 mo of therapy. It is suggested (1) that among the body composition parameters studied, muscle mass is the tissue most closely reflecting the lack of HGH and also its therapeutic benefits and (2) evaluation of body composition in hypopituitary dwarfs in response to HGH therapy shows striking changes not reflected by the determination of stature or weight alone."}
{"id": "PMID:222312", "title": "Radiotherapy alone or with chemotherapy in the treatment of small-cell carcinoma of the lung. Medical Research Council Lung Cancer Working Party.", "content": "This report gives the complete findings at one year of a study comparing radiotherapy (Rt) with radiotherapy followed by 3-drug chemotherapy (RtC3) in the treatment of histologically proven small-cell carcinoma of the lung of limited extent. Over the 12-month period there was a significantly increased survival for the RtC3 patients (P = 0.002) and at 12 months 18% of the 121 Rt but 34% of the 115 RtC3 patients were alive (P = 0.009). The median survival for the Rt series was 25 weeks and for the RtC3 series 43 weeks. There was evidence of recurrence of the primary cancer in 32 (32%) of the 99 Rt and 20 (26%) of the 76 RtC3 patients who died. Distant metastases appeared earlier and were more frequent in the Rt series (P less than 0.0001) and over the 12-month period 79% of the Rt and 57% of the RtC3 patients developed distant metastases (P less than 0.0005). At 12 months only 8% of the Rt but 26% of the RtC3 patients were alive and free of metastases. Adverse reactions occurred much more frequently in the RtC3 series; 32% of the Rt series as against 83% of the RtC3 series had reactions, the most common being nausea and vomiting (13% Rt, 71% RtC3) and the most serious being marrow depression (23% Rt, 54% RtC3). No important differences were found among the survivors in the 2 series at 3, 6 or 12 months, in general condition, physical activity or respiratory function. It is concluded that radiotherapy plus chemotherapy was superior to radiotherapy alone, although chemotherapy did not protect patients from recurrence of primary growth.", "contents": "Radiotherapy alone or with chemotherapy in the treatment of small-cell carcinoma of the lung. Medical Research Council Lung Cancer Working Party. This report gives the complete findings at one year of a study comparing radiotherapy (Rt) with radiotherapy followed by 3-drug chemotherapy (RtC3) in the treatment of histologically proven small-cell carcinoma of the lung of limited extent. Over the 12-month period there was a significantly increased survival for the RtC3 patients (P = 0.002) and at 12 months 18% of the 121 Rt but 34% of the 115 RtC3 patients were alive (P = 0.009). The median survival for the Rt series was 25 weeks and for the RtC3 series 43 weeks. There was evidence of recurrence of the primary cancer in 32 (32%) of the 99 Rt and 20 (26%) of the 76 RtC3 patients who died. Distant metastases appeared earlier and were more frequent in the Rt series (P less than 0.0001) and over the 12-month period 79% of the Rt and 57% of the RtC3 patients developed distant metastases (P less than 0.0005). At 12 months only 8% of the Rt but 26% of the RtC3 patients were alive and free of metastases. Adverse reactions occurred much more frequently in the RtC3 series; 32% of the Rt series as against 83% of the RtC3 series had reactions, the most common being nausea and vomiting (13% Rt, 71% RtC3) and the most serious being marrow depression (23% Rt, 54% RtC3). No important differences were found among the survivors in the 2 series at 3, 6 or 12 months, in general condition, physical activity or respiratory function. It is concluded that radiotherapy plus chemotherapy was superior to radiotherapy alone, although chemotherapy did not protect patients from recurrence of primary growth."}
{"id": "PMID:222313", "title": "The nature of the copper atoms of cytochrome c oxidase as studied by optical and x-ray absorption edge spectroscopy.", "content": "X-ray absorption edge spectroscopy has been used to study the copper of 1--2 mM cytochrome c oxidase in the resting oxidized, mixed-valence, and fully reduced states. A comparison was made of this protein with copper complexes and with natural and artificial copper proteins. Spectra were obtained with synchrotron radiation from the SPEAR storage ring using highly sensitive fluorescence detectors. Temperatures of -80 to -120 degrees C were employed further to improve the stability of the samples and to avoid the possibility of either auto- or photon-induced reduction of the materials, which might have occurred in previous studies. In order to characterize the valence states of the Cu and Fe components, the samples were monitored by infrared and visible spectroscopy before and after irradiation by the X-ray beam. The combination of the optical and X-ray absorption techniques has afforded a deconvolution of the four species of copper in the various states of cytochrome c oxidase and the tentative assignment of Cu alpha, the copper redox coupled to the heme alpha of cytochrome alpha, as a highly covalent type of copper and Cu alpha 3, the copper of cytochrome alpha 3, as a more ionic 'blue' type I copper. The implications of these findings upon the mechanism of action of cytochrome oxidase are briefly outlined.", "contents": "The nature of the copper atoms of cytochrome c oxidase as studied by optical and x-ray absorption edge spectroscopy. X-ray absorption edge spectroscopy has been used to study the copper of 1--2 mM cytochrome c oxidase in the resting oxidized, mixed-valence, and fully reduced states. A comparison was made of this protein with copper complexes and with natural and artificial copper proteins. Spectra were obtained with synchrotron radiation from the SPEAR storage ring using highly sensitive fluorescence detectors. Temperatures of -80 to -120 degrees C were employed further to improve the stability of the samples and to avoid the possibility of either auto- or photon-induced reduction of the materials, which might have occurred in previous studies. In order to characterize the valence states of the Cu and Fe components, the samples were monitored by infrared and visible spectroscopy before and after irradiation by the X-ray beam. The combination of the optical and X-ray absorption techniques has afforded a deconvolution of the four species of copper in the various states of cytochrome c oxidase and the tentative assignment of Cu alpha, the copper redox coupled to the heme alpha of cytochrome alpha, as a highly covalent type of copper and Cu alpha 3, the copper of cytochrome alpha 3, as a more ionic 'blue' type I copper. The implications of these findings upon the mechanism of action of cytochrome oxidase are briefly outlined."}
{"id": "PMID:222314", "title": "Cyclic AMP induces the synthesis of developmentally regulated plasma membrane proteins in Dictyostelium.", "content": "Dictyostelium discoideum slugs (pseudoplasmodia) were disaggregated and the resynthesis of developmentally regulated plasma membrane proteins examined. The synthesis of the majority of these proteins was inhibited when cells were overlaid with Cellophane and maintained as a monolayer. However, cell contact and movement did occur under the Cellophane. The inhibition of differentiation may result from the inability of the cells to organize specifically into multicellular aggregates. The addition of cyclic AMP (1--5 mM) induced the synthesis of certain developmentally regulated plasma membrane proteins in cells overlaid with Cellophane. Hence, this confirms other work showing that cyclic AMP is required for at least some post-aggregative gene expression. Specific cell organisation and interactions are apparently required for an increase in or maintenance of intracellular cyclic AMP levels.", "contents": "Cyclic AMP induces the synthesis of developmentally regulated plasma membrane proteins in Dictyostelium. Dictyostelium discoideum slugs (pseudoplasmodia) were disaggregated and the resynthesis of developmentally regulated plasma membrane proteins examined. The synthesis of the majority of these proteins was inhibited when cells were overlaid with Cellophane and maintained as a monolayer. However, cell contact and movement did occur under the Cellophane. The inhibition of differentiation may result from the inability of the cells to organize specifically into multicellular aggregates. The addition of cyclic AMP (1--5 mM) induced the synthesis of certain developmentally regulated plasma membrane proteins in cells overlaid with Cellophane. Hence, this confirms other work showing that cyclic AMP is required for at least some post-aggregative gene expression. Specific cell organisation and interactions are apparently required for an increase in or maintenance of intracellular cyclic AMP levels."}
{"id": "PMID:222315", "title": "The decreased membrane fluidity of in vivo aged, human erythrocytes. A spin label study.", "content": "The decreased membrane fluidity of the in vivo aged, human erythrocytes is found, by monitoring the electron paramagnetic resonance (EPR) spectra of fatty acid spin labels incorporated into the membrane. In addition, the decreased cell sizes and the decreased cholesterol and phospholipids contents, without significant changes of the quantity of the membrane proteins, also the decrease of ATP and 2,3-diphosphoglycerate and the increase of ADP and AMP, in the aged cells, were observed. Further the functional impairments of the aged cells, i.e. the increased oxygen affinity and the decreased deformability, were shown. On the basis of these quantitative data, the alteration of the protein-lipid organization, due to decreased lipid/protein ratio, the modified protein-lipid interaction and/or the influences of the diminished ATP content, is suggested to contribute towards the decreased membrane fluidity of the in vivo aged erythrocytes.", "contents": "The decreased membrane fluidity of in vivo aged, human erythrocytes. A spin label study. The decreased membrane fluidity of the in vivo aged, human erythrocytes is found, by monitoring the electron paramagnetic resonance (EPR) spectra of fatty acid spin labels incorporated into the membrane. In addition, the decreased cell sizes and the decreased cholesterol and phospholipids contents, without significant changes of the quantity of the membrane proteins, also the decrease of ATP and 2,3-diphosphoglycerate and the increase of ADP and AMP, in the aged cells, were observed. Further the functional impairments of the aged cells, i.e. the increased oxygen affinity and the decreased deformability, were shown. On the basis of these quantitative data, the alteration of the protein-lipid organization, due to decreased lipid/protein ratio, the modified protein-lipid interaction and/or the influences of the diminished ATP content, is suggested to contribute towards the decreased membrane fluidity of the in vivo aged erythrocytes."}
{"id": "PMID:222316", "title": "ESR determination of membrane order parameter in yeast sterol mutants.", "content": "ESR investigations designed to determine membrane order parameter in sterol mutants of Saccharomyces cerevisiae were conducted using the membrane probe, 5-doxyl stearic acid. These mutants are blocked in the ergosterol biosynthetic pathway and thus do not synthesize ergosterol, the end product sterol. They do not require exogenous ergosterol for growth and, therefore, incorporate ergosterol biosynthetic intermediates in their membrane. Increasing order parameter is reflective of an increase in membrane rigidity. Single mutants involving B-ring delta 8 leads to delta 7 isomerization (erg 2) and C-24 methylation (erg 6) showed greater membrane rigidity than wild-type during exponential growth. A double mutant containing both lesions (erg 6/2) showed an even greater degree of membrane rigidity. During stationary phase the order of decreasing membrane rigidity was erg 6 greater than erg 6/2 greater than erg 2 = wild-type. The increased membrane order parameter was attributed to the presence of substituted sterols rather than increased sterol content or altered fatty acid synthesis.", "contents": "ESR determination of membrane order parameter in yeast sterol mutants. ESR investigations designed to determine membrane order parameter in sterol mutants of Saccharomyces cerevisiae were conducted using the membrane probe, 5-doxyl stearic acid. These mutants are blocked in the ergosterol biosynthetic pathway and thus do not synthesize ergosterol, the end product sterol. They do not require exogenous ergosterol for growth and, therefore, incorporate ergosterol biosynthetic intermediates in their membrane. Increasing order parameter is reflective of an increase in membrane rigidity. Single mutants involving B-ring delta 8 leads to delta 7 isomerization (erg 2) and C-24 methylation (erg 6) showed greater membrane rigidity than wild-type during exponential growth. A double mutant containing both lesions (erg 6/2) showed an even greater degree of membrane rigidity. During stationary phase the order of decreasing membrane rigidity was erg 6 greater than erg 6/2 greater than erg 2 = wild-type. The increased membrane order parameter was attributed to the presence of substituted sterols rather than increased sterol content or altered fatty acid synthesis."}
{"id": "PMID:222317", "title": "Infinite cis influx of cyclic AMP into human erythrocyte ghosts.", "content": "Infinite cis uptake of cyclic AMP into red blood cell ghosts has been measured. The Koiic is calculated from two different integrated rate equations that are applicable when the substrate concentration is unsufficient to cause volume changes. Values of 0.69 mM and 0.66 mM are obtained for the infinite cis Km at 30 degrees C using these procedures. These values are only slightly higher than that predicted from zero trans net flux experiments. Lowering the temperature reduces Koiic from 0.69 mM at 30 degrees C to 0.478 mM at 20 degrees C, 0.108 mM at 10 degrees C and 0.072 mM at 4 degrees C (Q10 = 2.4). The Q10 for activation of influx permeability of 10(-5) M cyclic AMP is 1.55.", "contents": "Infinite cis influx of cyclic AMP into human erythrocyte ghosts. Infinite cis uptake of cyclic AMP into red blood cell ghosts has been measured. The Koiic is calculated from two different integrated rate equations that are applicable when the substrate concentration is unsufficient to cause volume changes. Values of 0.69 mM and 0.66 mM are obtained for the infinite cis Km at 30 degrees C using these procedures. These values are only slightly higher than that predicted from zero trans net flux experiments. Lowering the temperature reduces Koiic from 0.69 mM at 30 degrees C to 0.478 mM at 20 degrees C, 0.108 mM at 10 degrees C and 0.072 mM at 4 degrees C (Q10 = 2.4). The Q10 for activation of influx permeability of 10(-5) M cyclic AMP is 1.55."}
{"id": "PMID:222318", "title": "Sidedness of the ATP-Na+-K+ interactions with the Na+ pump in squid axons.", "content": "Using dialysed squid axons we have been able to control internal and external ionic compositions under conditions in which most of the Na+ efflux goes through the Na+ pump. We found that (i) internal K+ had a strong inhibitory effect on Na+ efflux; this effect was antagonized by ATP, with low affinity, and by internal Na+, (ii) a reduction in ATP levels from 3 mM to 50 microM greatly increased the apparent affinity for external K+, but reduced its effectiveness compared with other monovalent cations, as an activator of Na+ efflux, and (iii) the relative effectiveness of different K+ congeners as external activator of the Na+ efflux, though affected by the ATP concentration, was not affected by the Na+/K+ ratio inside the cells. These results are consistent with the idea that the same conformation of the (Na+ + K+)-ATPase can be reached by interaction with external K+ after phosphorylation and with internal K+ before rephosphorylation. They also stress a nonphosphorylating regulatory role of ATP.", "contents": "Sidedness of the ATP-Na+-K+ interactions with the Na+ pump in squid axons. Using dialysed squid axons we have been able to control internal and external ionic compositions under conditions in which most of the Na+ efflux goes through the Na+ pump. We found that (i) internal K+ had a strong inhibitory effect on Na+ efflux; this effect was antagonized by ATP, with low affinity, and by internal Na+, (ii) a reduction in ATP levels from 3 mM to 50 microM greatly increased the apparent affinity for external K+, but reduced its effectiveness compared with other monovalent cations, as an activator of Na+ efflux, and (iii) the relative effectiveness of different K+ congeners as external activator of the Na+ efflux, though affected by the ATP concentration, was not affected by the Na+/K+ ratio inside the cells. These results are consistent with the idea that the same conformation of the (Na+ + K+)-ATPase can be reached by interaction with external K+ after phosphorylation and with internal K+ before rephosphorylation. They also stress a nonphosphorylating regulatory role of ATP."}
{"id": "PMID:222319", "title": "Effects of drugs on pigeon erythrocyte membrane and asymmetric control or adenylate cyclase by the lipid bilayer.", "content": "In pigeon erythrocyte membrane, the beta-adrenergic receptor and the enzyme adenylate cyclase can be uncoupled in two different ways depending on the type of drug used. Cationic drugs: chlorpromazine, methochlorpromazine, tetracaine, n-octylamine and a neutral alcohol, octanol, abolished alprenolol receptor binding ability and in the same range of concentration of the drug, sensitized adenylate cyclase to fluoride or Gpp(NH)p stimulation. Anionic drugs: di- and trinitro-phenols, indomethacin and octanoic acid did not affect the total number of beta-adrenergic receptor sites and, with the exception of trinitrophenol, did not change the association constant for alprenolol but they abolished the stimulation of adenylate cyclase by isoproterenol, fluoride or Gpp(NH)p. These modifications of the adenylate cyclase system occurred in a range of drug concentration where cell shape and protection against hemolysis were also affected. As chemical composition varies widely from one drug to another, it is suggested that these effects are largely nonspecific and mediated by the lipid bilayer. They are probably related to a preferential sidedness of action of the drugs in the lipid bilayer, displaying the role of an asymmetric control of the adenylate cyclase system in the membrane by the two halves of this bilayer.", "contents": "Effects of drugs on pigeon erythrocyte membrane and asymmetric control or adenylate cyclase by the lipid bilayer. In pigeon erythrocyte membrane, the beta-adrenergic receptor and the enzyme adenylate cyclase can be uncoupled in two different ways depending on the type of drug used. Cationic drugs: chlorpromazine, methochlorpromazine, tetracaine, n-octylamine and a neutral alcohol, octanol, abolished alprenolol receptor binding ability and in the same range of concentration of the drug, sensitized adenylate cyclase to fluoride or Gpp(NH)p stimulation. Anionic drugs: di- and trinitro-phenols, indomethacin and octanoic acid did not affect the total number of beta-adrenergic receptor sites and, with the exception of trinitrophenol, did not change the association constant for alprenolol but they abolished the stimulation of adenylate cyclase by isoproterenol, fluoride or Gpp(NH)p. These modifications of the adenylate cyclase system occurred in a range of drug concentration where cell shape and protection against hemolysis were also affected. As chemical composition varies widely from one drug to another, it is suggested that these effects are largely nonspecific and mediated by the lipid bilayer. They are probably related to a preferential sidedness of action of the drugs in the lipid bilayer, displaying the role of an asymmetric control of the adenylate cyclase system in the membrane by the two halves of this bilayer."}
{"id": "PMID:222320", "title": "Accessibility of sialo components in a murine tumor cell to extracellular N-acetylneuraminate glycohydrolase (sialidase).", "content": "Lipid-bound sialic acid in the murine melanoma cell is not totally inaccessible to an exogenous macromolecular probe, as formerly believed. Roughly 30% of the dialic acid bound to lipid, and an equal proportion of the sialic acid bound to protein is cleaved by the action of Clostridium perfringens N-acetylneuraminate glycohydrolase (neuraminidase, sialidase) when the purified enzyme is added to the suspenion medium of intact murine melanoma cells freshly derived from the tumor. Cleavage of lipid-bound sialic acid is indifferent to the presence of Ca (2+) in the medium. However, maximum release from protein requires a physiological concentration of this divalent cation. Variation in ionic strength has no effect on release of sialic acid. These findings show that restricted portion of the bound sialic acid may be released from the intact murine melanama cell by the extracellularly supplied enzyme acting topographically.", "contents": "Accessibility of sialo components in a murine tumor cell to extracellular N-acetylneuraminate glycohydrolase (sialidase). Lipid-bound sialic acid in the murine melanoma cell is not totally inaccessible to an exogenous macromolecular probe, as formerly believed. Roughly 30% of the dialic acid bound to lipid, and an equal proportion of the sialic acid bound to protein is cleaved by the action of Clostridium perfringens N-acetylneuraminate glycohydrolase (neuraminidase, sialidase) when the purified enzyme is added to the suspenion medium of intact murine melanoma cells freshly derived from the tumor. Cleavage of lipid-bound sialic acid is indifferent to the presence of Ca (2+) in the medium. However, maximum release from protein requires a physiological concentration of this divalent cation. Variation in ionic strength has no effect on release of sialic acid. These findings show that restricted portion of the bound sialic acid may be released from the intact murine melanama cell by the extracellularly supplied enzyme acting topographically."}
{"id": "PMID:222321", "title": "Interaction of polyene antibiotics with sterols in phosphatidylcholine bilayer membranes as studied by spin probes.", "content": "Interaction of filipin and amphotericin B with sterols in phosphatidylcholine membranes has been studied using various spin probes; epiandrosterone, cholestanone, phosphatidylcholine with 12-nitroxide or 5-nitroxide stearate attached to 2 position and also with tempocholine at the head group. Filipin caused increase in the fluidity of cholesterol-containing phosphatidylcholine membranes near the center, while it rather decreased the fluidity near the polar surface. On the other hand, amphotericin B did not apparently affect the fluidity. In the electron spin resonance spectrum of steriod spin probes in the antibiotic-containing membranes, both bound and free signals were observed and the association constant was calculated from the siganal intensity. In the binding of steriods with filipin, both 3 and 17 positions were involved, while the 17 positions was less involved in the binding with amphotericin B. Phase change in the host membrane markedly affected the interaction of filipin with epiandrosterone probe. The bound fraction jumped from 0.4 to 0.8 on going to the crystalline state and increased further with decrease in temperature. The overall splitting of the bound signal also increased on lowering the temperature below phase transition. This change was attributed to aggregate formation of filipin-steriod complexes in the crystalline state. On the other hand, effect of phase transition was much smaller on the interaction of amphotericin B with the steriod probe.", "contents": "Interaction of polyene antibiotics with sterols in phosphatidylcholine bilayer membranes as studied by spin probes. Interaction of filipin and amphotericin B with sterols in phosphatidylcholine membranes has been studied using various spin probes; epiandrosterone, cholestanone, phosphatidylcholine with 12-nitroxide or 5-nitroxide stearate attached to 2 position and also with tempocholine at the head group. Filipin caused increase in the fluidity of cholesterol-containing phosphatidylcholine membranes near the center, while it rather decreased the fluidity near the polar surface. On the other hand, amphotericin B did not apparently affect the fluidity. In the electron spin resonance spectrum of steriod spin probes in the antibiotic-containing membranes, both bound and free signals were observed and the association constant was calculated from the siganal intensity. In the binding of steriods with filipin, both 3 and 17 positions were involved, while the 17 positions was less involved in the binding with amphotericin B. Phase change in the host membrane markedly affected the interaction of filipin with epiandrosterone probe. The bound fraction jumped from 0.4 to 0.8 on going to the crystalline state and increased further with decrease in temperature. The overall splitting of the bound signal also increased on lowering the temperature below phase transition. This change was attributed to aggregate formation of filipin-steriod complexes in the crystalline state. On the other hand, effect of phase transition was much smaller on the interaction of amphotericin B with the steriod probe."}
{"id": "PMID:222322", "title": "Alteration of human erythrocyte plasma membranes by perfringolysin O as revealed by freeze-fracture electron microscopy. Studies on Clostridium perfringens exotoxins V.", "content": "When human erythrocyte membranes were treated with perfringolysin O (Clostridium perfringens theta-toxin) and examined by electron microscopy after freeze-fracture, two ultrastructural alterations were observed in fracture faces of membrane. (1) A random aggregation of intramembranous particles was seen in the fracture face of the protoplasmic half (PF face) of all membranes treated with the toxin, even if at a low concentration (40 hemolytic units/ml). On the other hand, the aggregation in the fracture face of the exoplasmic half (EF face) was observed only in membranes treated with a high concentration (3300 hemolytic units/ml) for 2 h. (2) Round protrusions and \"cavities\" with 30 nm in diameter were visible in EF and PF faces of membranes treated with a high concentration, respectively. These structures were always protruded toward cytoplasmic side, but did not appear to form holes through the membrane. Ring and arc shaped structures with a dark center of 26 nm and a distinct border of 5 nm in width were observed when the toxin alone was negatively stained at a very high concentration (170,000 hemolytic units/ml). These structures were also produced in the presence of cholesterol even if the toxin concentration was low.", "contents": "Alteration of human erythrocyte plasma membranes by perfringolysin O as revealed by freeze-fracture electron microscopy. Studies on Clostridium perfringens exotoxins V. When human erythrocyte membranes were treated with perfringolysin O (Clostridium perfringens theta-toxin) and examined by electron microscopy after freeze-fracture, two ultrastructural alterations were observed in fracture faces of membrane. (1) A random aggregation of intramembranous particles was seen in the fracture face of the protoplasmic half (PF face) of all membranes treated with the toxin, even if at a low concentration (40 hemolytic units/ml). On the other hand, the aggregation in the fracture face of the exoplasmic half (EF face) was observed only in membranes treated with a high concentration (3300 hemolytic units/ml) for 2 h. (2) Round protrusions and \"cavities\" with 30 nm in diameter were visible in EF and PF faces of membranes treated with a high concentration, respectively. These structures were always protruded toward cytoplasmic side, but did not appear to form holes through the membrane. Ring and arc shaped structures with a dark center of 26 nm and a distinct border of 5 nm in width were observed when the toxin alone was negatively stained at a very high concentration (170,000 hemolytic units/ml). These structures were also produced in the presence of cholesterol even if the toxin concentration was low."}
{"id": "PMID:222323", "title": "Characterization of a proteolipid complex of aminoacyl-tRNA synthetases and transfer RNA from rat liver.", "content": "A high molecular weight complex containing aminoacyl-tRNA synthetases, peptidyl acetyltransferase, lipids and tRNA has been isolated from the 250,000 x g postmitochondrial supernatant from rat liver cells. Aminoacyl-tRNA synthetase activity directed towards arginine, aspartate, glutamine, glutamate, glycine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, and tyrosine is present. An endogenous pool of aminoacyladenylates is indicated by an ATP-32PPi exchange catalyzed by the native complex, which shows a dramatic increase after addition of ATP. Lysine is the only amino acid which greatly increases the exchange rate catalyzed by the native complex in vitro, whereas components of the denatured complex activate all the 13 amino acids in the presence of ATP. Six of the eight lipid fractions were glycolipids; cholesterol and cholesterol esters were absent. The extracted RNA has many characteristics of tRNA. These findings provide evidence for the organization of aminoacyl-tRNA synthetases in a complex with peptidyl acetyltransferase that also contains lipids and tRNA and that can be readily isolated from the cytosol of rat liver cells.", "contents": "Characterization of a proteolipid complex of aminoacyl-tRNA synthetases and transfer RNA from rat liver. A high molecular weight complex containing aminoacyl-tRNA synthetases, peptidyl acetyltransferase, lipids and tRNA has been isolated from the 250,000 x g postmitochondrial supernatant from rat liver cells. Aminoacyl-tRNA synthetase activity directed towards arginine, aspartate, glutamine, glutamate, glycine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, and tyrosine is present. An endogenous pool of aminoacyladenylates is indicated by an ATP-32PPi exchange catalyzed by the native complex, which shows a dramatic increase after addition of ATP. Lysine is the only amino acid which greatly increases the exchange rate catalyzed by the native complex in vitro, whereas components of the denatured complex activate all the 13 amino acids in the presence of ATP. Six of the eight lipid fractions were glycolipids; cholesterol and cholesterol esters were absent. The extracted RNA has many characteristics of tRNA. These findings provide evidence for the organization of aminoacyl-tRNA synthetases in a complex with peptidyl acetyltransferase that also contains lipids and tRNA and that can be readily isolated from the cytosol of rat liver cells."}
{"id": "PMID:222324", "title": "Removal of T4 endonuclease V-sensitive sites from SV40 DNA after exposure to ultraviolet light.", "content": "The induction and removal of sites sensitive to T4 endonuclease V from ultraviolet-irradiated Simian Virus 40 (SV40) Form I (supercoiled) DNA during a lytic infection of monkey CV-1 cells was investigated by agarose tube gel electrophoresis. Endonuclease-sensitive sites were induced at a rate of 0.049 sites/SV40 genome per J/m2, or 1.4 sites/1 . 10(8) daltons of DNA per J/m2. This value is similar to the yield of endonuclease-sensitive sites and pyrimidine dimers in uninfected host CV-1 cell DNA. Removal of endonuclease-sensitive sites was dose dependent and non-linear for at least 24 h after irradiation. These results suggest that SV40 DNA is subject to the excision repair mechanisms of the host cell, and that the excision of pyrimidine dimers may be one of the biochemical events underlying host cell reactivation.", "contents": "Removal of T4 endonuclease V-sensitive sites from SV40 DNA after exposure to ultraviolet light. The induction and removal of sites sensitive to T4 endonuclease V from ultraviolet-irradiated Simian Virus 40 (SV40) Form I (supercoiled) DNA during a lytic infection of monkey CV-1 cells was investigated by agarose tube gel electrophoresis. Endonuclease-sensitive sites were induced at a rate of 0.049 sites/SV40 genome per J/m2, or 1.4 sites/1 . 10(8) daltons of DNA per J/m2. This value is similar to the yield of endonuclease-sensitive sites and pyrimidine dimers in uninfected host CV-1 cell DNA. Removal of endonuclease-sensitive sites was dose dependent and non-linear for at least 24 h after irradiation. These results suggest that SV40 DNA is subject to the excision repair mechanisms of the host cell, and that the excision of pyrimidine dimers may be one of the biochemical events underlying host cell reactivation."}
{"id": "PMID:222325", "title": "Purification of mitochondrial NADH dehydrogenase from Drosophila hydei and comparison with the 'heat-shock' polypeptides.", "content": "Mitochondrial NADH dehydrogenase (NADH:(acceptor) oxidoreductase, EC .6.99.3) from either Drosophila hydei larvae or embryos has been purified 150- and 120-fold, respectively. The purified enzyme appeared homogeneous and showed a molecular weight of 57 000. The molecular weight of the nondenatured enzyme was 79 000. On isoelectro-focussing of the preparation, two fractions were observed, a major one with an isoelectric point of 6.2 and a minor fraction with an isoelectric point of 4.9. Straight-line kinetics in Lineweaver-Burk plots were observed for the purified enzyme with a Km of 0.040 mM. The Km was not changed during the purification procedure, suggesting that the enzyme was not denatured or inactivated. The pH optimum of the purified enzyme was 5.6. The molecular weight of the purified mitochondrial NADH dehydrogenase does not correspond to that of one of the 'heat-shock' polypeptides.", "contents": "Purification of mitochondrial NADH dehydrogenase from Drosophila hydei and comparison with the 'heat-shock' polypeptides. Mitochondrial NADH dehydrogenase (NADH:(acceptor) oxidoreductase, EC .6.99.3) from either Drosophila hydei larvae or embryos has been purified 150- and 120-fold, respectively. The purified enzyme appeared homogeneous and showed a molecular weight of 57 000. The molecular weight of the nondenatured enzyme was 79 000. On isoelectro-focussing of the preparation, two fractions were observed, a major one with an isoelectric point of 6.2 and a minor fraction with an isoelectric point of 4.9. Straight-line kinetics in Lineweaver-Burk plots were observed for the purified enzyme with a Km of 0.040 mM. The Km was not changed during the purification procedure, suggesting that the enzyme was not denatured or inactivated. The pH optimum of the purified enzyme was 5.6. The molecular weight of the purified mitochondrial NADH dehydrogenase does not correspond to that of one of the 'heat-shock' polypeptides."}
{"id": "PMID:222326", "title": "The nature of the substrate inhibition in lactate dehydrogenases as studied by a spin-labeled derivative of NAD.", "content": "The formation of the ternary complex of lactate dehydrogenase (L-lactate:NAD+ oxidoreductase, EC 1.1.1.27) from pig heart and skeletal muscle with the adduct of pyruvate to NAD\", spin-labeled at N6 was studied by ultraviolet spectroscopy and ESR techniques. According to ultraviolet measurements we found identical binding characteristics for the natural coenzyme and its spin-labeled analog. The rate by which the ESR signal of free spin-labeled NAD+ decreased upon addition of pyruvate to the binary complexes was substantially different in the two isozymes. With the heart type an initial drop followed by a further linear decrease, zero order in the enzyme and coenzyme concentration was observed. In case of the skeletal muscle isozyme no immediate reaction and a first order process occurred. The initial reaction can be attributed to a non-covalent enzyme/spin-labeled NAD+/pyruvate complex with a dissociation constant for pyruvate of 11 +/- 1 mM, thus explaining the well-known substrate inhibition in the heart isozyme above 2 mM pyruvate. The further reaction is then determined by the buffer dependent enolization of pyruvate. In the muscle isozyme formation of the covalent adduct is not assisted by prior binding of pyruvate in a non-covalent ternary complex and therefore the rate depends on the binary complex concentration.", "contents": "The nature of the substrate inhibition in lactate dehydrogenases as studied by a spin-labeled derivative of NAD. The formation of the ternary complex of lactate dehydrogenase (L-lactate:NAD+ oxidoreductase, EC 1.1.1.27) from pig heart and skeletal muscle with the adduct of pyruvate to NAD\", spin-labeled at N6 was studied by ultraviolet spectroscopy and ESR techniques. According to ultraviolet measurements we found identical binding characteristics for the natural coenzyme and its spin-labeled analog. The rate by which the ESR signal of free spin-labeled NAD+ decreased upon addition of pyruvate to the binary complexes was substantially different in the two isozymes. With the heart type an initial drop followed by a further linear decrease, zero order in the enzyme and coenzyme concentration was observed. In case of the skeletal muscle isozyme no immediate reaction and a first order process occurred. The initial reaction can be attributed to a non-covalent enzyme/spin-labeled NAD+/pyruvate complex with a dissociation constant for pyruvate of 11 +/- 1 mM, thus explaining the well-known substrate inhibition in the heart isozyme above 2 mM pyruvate. The further reaction is then determined by the buffer dependent enolization of pyruvate. In the muscle isozyme formation of the covalent adduct is not assisted by prior binding of pyruvate in a non-covalent ternary complex and therefore the rate depends on the binary complex concentration."}
{"id": "PMID:222327", "title": "Mechanism of inhibition of malate dehydrogenase by thyroxine derivatives and reactivation by antibodies: homogeneous enzyme immunoassay for thryroxine.", "content": "Pig heart mitochondrial malate dehydrogenase (L-malate:NAD+ oxidoreductase, EC 1.1.1.37) is about 90% inhibited upon labelling an average of two amino groups per subunit with an active ester of thyroxine. Inhibition is probably associated primarily with thyroxine binding to one specific group which is normally unreactive but becomes activated upon noncovalent binding of thyroxine derivatives to the enzyme. Enzyme inhibition is due to a decrease in the rate of association of NAD. Antibodies to thyroxine induce a slow conformational change with partial reversal of inhibition of more heavily labelled conjugates. The antibody-induced activation is not cooperative and does not require bivalent association of the antibody. Activation can be blocked by the presence of free thyroxine and is the basis for a clinically useful assay for serum thyroxine.", "contents": "Mechanism of inhibition of malate dehydrogenase by thyroxine derivatives and reactivation by antibodies: homogeneous enzyme immunoassay for thryroxine. Pig heart mitochondrial malate dehydrogenase (L-malate:NAD+ oxidoreductase, EC 1.1.1.37) is about 90% inhibited upon labelling an average of two amino groups per subunit with an active ester of thyroxine. Inhibition is probably associated primarily with thyroxine binding to one specific group which is normally unreactive but becomes activated upon noncovalent binding of thyroxine derivatives to the enzyme. Enzyme inhibition is due to a decrease in the rate of association of NAD. Antibodies to thyroxine induce a slow conformational change with partial reversal of inhibition of more heavily labelled conjugates. The antibody-induced activation is not cooperative and does not require bivalent association of the antibody. Activation can be blocked by the presence of free thyroxine and is the basis for a clinically useful assay for serum thyroxine."}
{"id": "PMID:222328", "title": "Hydrogenase activity in the dry state: isotope exchange and reversible oxidoreduction of cytochrome c3.", "content": "Hydrogenase (hydrogen:ferricytochrome c3 oxidoreductase, EC 1.12.2.1) catalyzes three types of reactions, i.e., (1) conversion between hydrogen modifications, para-H2 and ortho-H2, (2) exchange reaction between hydrogen isotopes, and (3) reversible oxidoreduction of an electron carrier with H2 and protons. We observed that purified desulfovibrio hydrogenase in the dry state could catalyze not only the conversion and exchange reactions (Yagi, T., Tsuda, M., Mori, Y. and Inokuchi, H. (1969) J. Am. Chem. Soc. 91, 2801) but also the reversible oxidoreduction of the electron carrier, cytochrome c3 with H2. The rate of the conversion was in the range from 0.1 to 0.65 mol H2 converted per mol hydrogenase per s, and the ratio of the conversion rate to the exchange rate was near 5. The rate of oxidoreduction of cytochrome c3 in the dry state was 0.015 mol H2 taken up in the forward reaction and 0.003 mol H2 released in the reverse reaction per mol hydrogenase per s. The process of these reactions could be explained by the observations that the hydrogenase molecule in the dry state has protons which are directly exchangeable with H2 during catalytic process. The reversible oxidoreduction of cytochrome c3 is also explained by inter- and intramolecular electron transfer among cytochrome c3 molecules.", "contents": "Hydrogenase activity in the dry state: isotope exchange and reversible oxidoreduction of cytochrome c3. Hydrogenase (hydrogen:ferricytochrome c3 oxidoreductase, EC 1.12.2.1) catalyzes three types of reactions, i.e., (1) conversion between hydrogen modifications, para-H2 and ortho-H2, (2) exchange reaction between hydrogen isotopes, and (3) reversible oxidoreduction of an electron carrier with H2 and protons. We observed that purified desulfovibrio hydrogenase in the dry state could catalyze not only the conversion and exchange reactions (Yagi, T., Tsuda, M., Mori, Y. and Inokuchi, H. (1969) J. Am. Chem. Soc. 91, 2801) but also the reversible oxidoreduction of the electron carrier, cytochrome c3 with H2. The rate of the conversion was in the range from 0.1 to 0.65 mol H2 converted per mol hydrogenase per s, and the ratio of the conversion rate to the exchange rate was near 5. The rate of oxidoreduction of cytochrome c3 in the dry state was 0.015 mol H2 taken up in the forward reaction and 0.003 mol H2 released in the reverse reaction per mol hydrogenase per s. The process of these reactions could be explained by the observations that the hydrogenase molecule in the dry state has protons which are directly exchangeable with H2 during catalytic process. The reversible oxidoreduction of cytochrome c3 is also explained by inter- and intramolecular electron transfer among cytochrome c3 molecules."}
{"id": "PMID:222330", "title": "Ethanediol monoester hydrolysis by monoacylglycerol lipase of rat liver microsomes.", "content": "The hydrolysis of long-chain monoester of ethanediol by rat,liver subcellular fractions was investigated in order to define the carboxylic acid ester hydrolase involved and to localize the enzymic activity. We found that with 1-O-hexadecanoyl [U-14C]ethanediol as substrate, hydrolytic activity was foremost associated with the rough microsomal fraction. The pH optimum occurred at 8.5. The apparent Km and V values were 6.5 . 10(-4) M and 13 mumol/h per mg microsomal protein, respectively. Enzymic activity was inhibited by p-chloromercuribenzoate and by diisopropylfluorophosphate, whereas NaF was less effective and CaCl2 did not affect apparent activity. Amongst a number of carboxylic acid esters tested as substrate, only long-chain 1-acyl and 2-acyl glycerols inhibited acyl diol hydrolysis competitively (Ki approximately 0.9 mM). It was concluded that long-chain monoesters of ethanediol are hydrolyzed by the monoacyl glycerol lipase system associated with the rat liver microsomal fraction. Because diol monoester is also utilized by the cholinephosphotransferase system of liver to form highly lytic acyl diol phosphocholines, efficient diol monoester hydrolysis by monoglyceride lipase may be a significant step in regulating acyl diol phosphocholine levels in biological systems.", "contents": "Ethanediol monoester hydrolysis by monoacylglycerol lipase of rat liver microsomes. The hydrolysis of long-chain monoester of ethanediol by rat,liver subcellular fractions was investigated in order to define the carboxylic acid ester hydrolase involved and to localize the enzymic activity. We found that with 1-O-hexadecanoyl [U-14C]ethanediol as substrate, hydrolytic activity was foremost associated with the rough microsomal fraction. The pH optimum occurred at 8.5. The apparent Km and V values were 6.5 . 10(-4) M and 13 mumol/h per mg microsomal protein, respectively. Enzymic activity was inhibited by p-chloromercuribenzoate and by diisopropylfluorophosphate, whereas NaF was less effective and CaCl2 did not affect apparent activity. Amongst a number of carboxylic acid esters tested as substrate, only long-chain 1-acyl and 2-acyl glycerols inhibited acyl diol hydrolysis competitively (Ki approximately 0.9 mM). It was concluded that long-chain monoesters of ethanediol are hydrolyzed by the monoacyl glycerol lipase system associated with the rat liver microsomal fraction. Because diol monoester is also utilized by the cholinephosphotransferase system of liver to form highly lytic acyl diol phosphocholines, efficient diol monoester hydrolysis by monoglyceride lipase may be a significant step in regulating acyl diol phosphocholine levels in biological systems."}
{"id": "PMID:222331", "title": "Purification of human plasma lecithin:cholesterol acyltransferase and its specificity towards the acyl acceptor.", "content": "A simple and convenient method for the purification of human plasma lecithin-cholesterol acyltransferase was developed. The method involves the adsorption of the enzyme from diluted human plasma on DEAE-Sephadex, treatment with 1-butanol in the presence of (NH4)2SO4, DEAE-Sephadex chromatography, treatment with dextran sulfate in the presence of Ca2+, and hydroxyapatite chromatography. The enzyme purified showed a single main band by polyacrylamide gel electrophoresis in the presence and absence of sodium dodecyl sulfate. In addition, the enzyme obtained was stable for more than four weeks, when it was kept at 4 degrees C under N2 in a buffer of low ionic strength. The purified enzyme was used to study its specificity toward the acyl acceptor. This specificity was found to be broad in that not only sterols but also long chain primary alcohols exhibited considerable acceptor activity. Furthermore, in agreement with our previous observations with crude enzyme (Piran, U. and Nishida, T. (1976) J. Biochem. (Tokyo) 80, 887-889), the purified enzyme was found to be capable of hydrolyzing the ester linkage at the carbon-2 position of phosphatidylcholine. The transesterification, as well as the hydrolytic reaction, required the presence of the cofactor polypeptide, apolipoprotein A-I.", "contents": "Purification of human plasma lecithin:cholesterol acyltransferase and its specificity towards the acyl acceptor. A simple and convenient method for the purification of human plasma lecithin-cholesterol acyltransferase was developed. The method involves the adsorption of the enzyme from diluted human plasma on DEAE-Sephadex, treatment with 1-butanol in the presence of (NH4)2SO4, DEAE-Sephadex chromatography, treatment with dextran sulfate in the presence of Ca2+, and hydroxyapatite chromatography. The enzyme purified showed a single main band by polyacrylamide gel electrophoresis in the presence and absence of sodium dodecyl sulfate. In addition, the enzyme obtained was stable for more than four weeks, when it was kept at 4 degrees C under N2 in a buffer of low ionic strength. The purified enzyme was used to study its specificity toward the acyl acceptor. This specificity was found to be broad in that not only sterols but also long chain primary alcohols exhibited considerable acceptor activity. Furthermore, in agreement with our previous observations with crude enzyme (Piran, U. and Nishida, T. (1976) J. Biochem. (Tokyo) 80, 887-889), the purified enzyme was found to be capable of hydrolyzing the ester linkage at the carbon-2 position of phosphatidylcholine. The transesterification, as well as the hydrolytic reaction, required the presence of the cofactor polypeptide, apolipoprotein A-I."}
{"id": "PMID:222332", "title": "Preparative isoelectric focussing of apolipoproteins C and E from human very low density lipoproteins.", "content": "The application of isoelectric focussing on a gel-stabilized layer for the separation of the Tris-urea-soluble apolipoproteins of very low density lipoproteins has been described. This method in one step, allows the separation of most apolipoproteins, which were then analyzed and characterized. Apolipoproteins CII and CI were isolated as single protein bands with apparent pI of 5.0 and 6.5, respectively. Apolipoprotein CII was biologically active and could activate lipoprotein lipase. Apolipoprotein CIII was separated into several protein bands with pI ranging from 4.7 to 5.1 as a function of their number of sialic acid residues. Apolipoprotein E was isolated and characterized into five polymorphic bands with pI of 5.7, 5.8, 5.9, 6.0, and 6.2, respectively.", "contents": "Preparative isoelectric focussing of apolipoproteins C and E from human very low density lipoproteins. The application of isoelectric focussing on a gel-stabilized layer for the separation of the Tris-urea-soluble apolipoproteins of very low density lipoproteins has been described. This method in one step, allows the separation of most apolipoproteins, which were then analyzed and characterized. Apolipoproteins CII and CI were isolated as single protein bands with apparent pI of 5.0 and 6.5, respectively. Apolipoprotein CII was biologically active and could activate lipoprotein lipase. Apolipoprotein CIII was separated into several protein bands with pI ranging from 4.7 to 5.1 as a function of their number of sialic acid residues. Apolipoprotein E was isolated and characterized into five polymorphic bands with pI of 5.7, 5.8, 5.9, 6.0, and 6.2, respectively."}
{"id": "PMID:222333", "title": "The demonstration of very low density lipoprotein in the basal lamina of the granulosa layer in the hen's ovarian follicle.", "content": "The isolated basal lamina from the granulosa layer in ovarian follicles of the domestic fowl contains an abundance of spherical particles with a modal cross-sectional diameter of 25-30 nm. The lipid in this basal lamina is predominantly triacylglycerol and its total fatty acid composition resembles that of plasma very low density lipoprotein (VLDL). Immunodiffusion studies and immunoelectrophoresis indicated that this basal lamina contains diffusible antigen identifiable with plasma VLDL. Perfusion with an alkaline buffer displaced the particles from the basal lamina and subsequent perfusion with plasma VLDL in an acidic buffer resulted in the reappearance of particles of similar size and form. Alternatively, when the perfused basal lamina was subsequently perfused with VLDL-free serum, few particulate structures were observed. Measurements of total and VLDL triacylglycerol together with electron microscope studies of the untreated and of the perfused basal lamina provided further evidence for the identification of the majority of particles with plasma VLDL. Other particulate lipoprotein is most probably plasma low density lipoprotein (LDL). These studies demonstrated that this basal lamina is permeable to the circulating VLDL of the laying fowl.", "contents": "The demonstration of very low density lipoprotein in the basal lamina of the granulosa layer in the hen's ovarian follicle. The isolated basal lamina from the granulosa layer in ovarian follicles of the domestic fowl contains an abundance of spherical particles with a modal cross-sectional diameter of 25-30 nm. The lipid in this basal lamina is predominantly triacylglycerol and its total fatty acid composition resembles that of plasma very low density lipoprotein (VLDL). Immunodiffusion studies and immunoelectrophoresis indicated that this basal lamina contains diffusible antigen identifiable with plasma VLDL. Perfusion with an alkaline buffer displaced the particles from the basal lamina and subsequent perfusion with plasma VLDL in an acidic buffer resulted in the reappearance of particles of similar size and form. Alternatively, when the perfused basal lamina was subsequently perfused with VLDL-free serum, few particulate structures were observed. Measurements of total and VLDL triacylglycerol together with electron microscope studies of the untreated and of the perfused basal lamina provided further evidence for the identification of the majority of particles with plasma VLDL. Other particulate lipoprotein is most probably plasma low density lipoprotein (LDL). These studies demonstrated that this basal lamina is permeable to the circulating VLDL of the laying fowl."}
{"id": "PMID:222334", "title": "Association of lysolecithin acyltransferase with the high density lipoproteins and its activation by the low density lipoproteins in normal human plasma.", "content": "The lysolecithin acyltransferase of human plasma is shown to be associated with the high-density lipoprotein fraction. Although the low density lipoproteins do not have intrinsic enzyme activity, their presence activated the enzyme 3--7-fold. This activation is not affected by heat-treatment of the low density lipoproteins, but is abolished by the addition of heparin.", "contents": "Association of lysolecithin acyltransferase with the high density lipoproteins and its activation by the low density lipoproteins in normal human plasma. The lysolecithin acyltransferase of human plasma is shown to be associated with the high-density lipoprotein fraction. Although the low density lipoproteins do not have intrinsic enzyme activity, their presence activated the enzyme 3--7-fold. This activation is not affected by heat-treatment of the low density lipoproteins, but is abolished by the addition of heparin."}
{"id": "PMID:222335", "title": "Reduction of ferricytochrome c, methemoglobin and metmyoglobin by hydroxyl and alcohol radicals.", "content": "We have studied the reaction of ferricytochrome c, methemoglobin and metmyoglobin with OH and alcohol radicals (methanol, ethanol, ethylene glycol and glycerol). These radicals can be divided into three groups: 1. The OH radicals which reduce the ferricytochrome c with a yield of (30 +/- 10)% and methemoglobin with a yield of (40 +/- 10)%. They do not reduce metmyoglobin. The reduction is not a normal bimolecular reaction but is most probably an intramolecular electron transfer of a protein radical. 2. Methanol and ethanol radicals which reduce all three hemoproteins with a yield of (100 +/- 5)%. This reduction is a normal bimolecular reaction. 3. Glycerol radicals which do not reduce the ferrihemoproteins under our experimental conditions. Ethylene glycol radicals do not reduce ferricytochrome c and metmyoglobin but they do reduce methemoglobin with a yield of (30 +/- 10)%.", "contents": "Reduction of ferricytochrome c, methemoglobin and metmyoglobin by hydroxyl and alcohol radicals. We have studied the reaction of ferricytochrome c, methemoglobin and metmyoglobin with OH and alcohol radicals (methanol, ethanol, ethylene glycol and glycerol). These radicals can be divided into three groups: 1. The OH radicals which reduce the ferricytochrome c with a yield of (30 +/- 10)% and methemoglobin with a yield of (40 +/- 10)%. They do not reduce metmyoglobin. The reduction is not a normal bimolecular reaction but is most probably an intramolecular electron transfer of a protein radical. 2. Methanol and ethanol radicals which reduce all three hemoproteins with a yield of (100 +/- 5)%. This reduction is a normal bimolecular reaction. 3. Glycerol radicals which do not reduce the ferrihemoproteins under our experimental conditions. Ethylene glycol radicals do not reduce ferricytochrome c and metmyoglobin but they do reduce methemoglobin with a yield of (30 +/- 10)%."}
{"id": "PMID:222336", "title": "A novel method for converting apolipoprotein B, the major protein moiety of human plasma low density lipoproteins, into a water-soluble protein.", "content": "We have developed a new technique to solubilize apolipoprotein B (ApoB) in aqueous solutions. The procedure involves stirring ApoB in 6 M guanidine/20 mM NH4Cl/NH4OH in the presence of cupric ammonia complexes at pH 9.7 for 20 h in N2, and then removing these reagents by a series of dialysis in N2. The resulting Cu(NH3)4(2)+-treated (Cu2+-treated) ApoB is soluble in aqueous buffers of pH above 8.3 or below 3. Parallel experiments carried out on control proteins, human albumin, alpha-lactalbumin, and insulin, indicated no change in molecular weight and no creation of a new NH2-terminal amino acid after Cu2+-treatment. By Edman degradation, the Cu2+-treated ApoB showed no detectable NH2-terminal amino acid. These results showed that the mechanism of Cu2+-solubilization of ApoB was not due to the cleavage of peptide bonds. Electrophoresis on urea-polyacrylamide gel, Cu2+-treated ApoB showed the same number of bands as the non-treated ApoB in the separating gels (7%) near the cathode, suggesting the heterogeneity of ApoB. In SDS-polyacrylamide gel (10%), the reduced and Cu2+-treated ApoB migrated with the similar mobilities to the monomer or dimer of human albumin. Antibodies raised against Cu2+-treated ApoB gave at least two immunoprecipitin lines against the Cu2+-treated ApoB as well as the non-treated guanidine-HCl-soluble ApoB, suggesting the presence of non-identical subunits.", "contents": "A novel method for converting apolipoprotein B, the major protein moiety of human plasma low density lipoproteins, into a water-soluble protein. We have developed a new technique to solubilize apolipoprotein B (ApoB) in aqueous solutions. The procedure involves stirring ApoB in 6 M guanidine/20 mM NH4Cl/NH4OH in the presence of cupric ammonia complexes at pH 9.7 for 20 h in N2, and then removing these reagents by a series of dialysis in N2. The resulting Cu(NH3)4(2)+-treated (Cu2+-treated) ApoB is soluble in aqueous buffers of pH above 8.3 or below 3. Parallel experiments carried out on control proteins, human albumin, alpha-lactalbumin, and insulin, indicated no change in molecular weight and no creation of a new NH2-terminal amino acid after Cu2+-treatment. By Edman degradation, the Cu2+-treated ApoB showed no detectable NH2-terminal amino acid. These results showed that the mechanism of Cu2+-solubilization of ApoB was not due to the cleavage of peptide bonds. Electrophoresis on urea-polyacrylamide gel, Cu2+-treated ApoB showed the same number of bands as the non-treated ApoB in the separating gels (7%) near the cathode, suggesting the heterogeneity of ApoB. In SDS-polyacrylamide gel (10%), the reduced and Cu2+-treated ApoB migrated with the similar mobilities to the monomer or dimer of human albumin. Antibodies raised against Cu2+-treated ApoB gave at least two immunoprecipitin lines against the Cu2+-treated ApoB as well as the non-treated guanidine-HCl-soluble ApoB, suggesting the presence of non-identical subunits."}
{"id": "PMID:222337", "title": "Receptor binding and conformational properties of bovine and ovine prolactins after chemical modification of the two tryptophan residues.", "content": "The two tryptophan residues in ovine and bovine prolactins were modified by reaction with 2-nitrophenylsulfenyl chloride in 75% formic acid. These derivatives exhibited an important loss of receptor affinity (less than 1% of the native hormones) to a rabbit mammary gland preparation. To a lesser degree, they also lost their binding affinity to specific guinea pig antibodies as detected by radioimmunoassay. The chemical modifications induced a change in the folding of the polypeptide chain, which in itself could be partly or totally responsible for the loss of biological or binding activities. This conformational change has been analyzed by circular dichroism and by prediction of secondary structures from the amino acid sequence using the method of Garnier et al. (Garnier, J., Osguthorpe, D.J. and Robson, B. (1978) J. Mol. Biol. 120, 97--120). The comparison of predicted prolactin and somatotropin structures revealed almost identical alpha-helix, turns and coil regions with an overall content of 67% alpha-helix, 5% beta-sheet, 17% turn and 11% of aperiodic structures. These values were close to those obtained from circular dichroism. The conformational change of the chemically modified hormones as compared to native folding, can be described as a partial loss of alpha-helical structure and an increase in beta-sheet content.", "contents": "Receptor binding and conformational properties of bovine and ovine prolactins after chemical modification of the two tryptophan residues. The two tryptophan residues in ovine and bovine prolactins were modified by reaction with 2-nitrophenylsulfenyl chloride in 75% formic acid. These derivatives exhibited an important loss of receptor affinity (less than 1% of the native hormones) to a rabbit mammary gland preparation. To a lesser degree, they also lost their binding affinity to specific guinea pig antibodies as detected by radioimmunoassay. The chemical modifications induced a change in the folding of the polypeptide chain, which in itself could be partly or totally responsible for the loss of biological or binding activities. This conformational change has been analyzed by circular dichroism and by prediction of secondary structures from the amino acid sequence using the method of Garnier et al. (Garnier, J., Osguthorpe, D.J. and Robson, B. (1978) J. Mol. Biol. 120, 97--120). The comparison of predicted prolactin and somatotropin structures revealed almost identical alpha-helix, turns and coil regions with an overall content of 67% alpha-helix, 5% beta-sheet, 17% turn and 11% of aperiodic structures. These values were close to those obtained from circular dichroism. The conformational change of the chemically modified hormones as compared to native folding, can be described as a partial loss of alpha-helical structure and an increase in beta-sheet content."}
{"id": "PMID:222338", "title": "Multiple forms of an extracellular cyclic-AMP phosphodiesterase from Dictyostelium discoideum.", "content": "The extracellular cyclic-AMP phosphodiesterase of a mutant of Dictyostelium discoideum which accumulates this enzyme was found to exist in multiple forms. Using the isoelectric focusing technique the phosphodiesterase activity was distributed into three peaks with isoelectric points of 4.6, 6.5 and 8.3, designated as p4, p6 and p8. Gel filtration and sucrose gradient analysis showed that the p4 activity consisted of two forms of different sedimentation coefficients. At high enzyme concentrations, the heavy form was favored. Dilution of enzyme activity shifted the equilibrium toward the light form. Direct analysis by sucrose gradient sedimentation of all isoelectric forms demonstrated that besides p4, p6 activity also existed as a mixture of the heavy (9.7 S) and the light (5.4 S) components. In contrast, the p8 activity displayed only the light form. The heterogeneity of the p4 and p6 isoelectric forms was also observed by polyacrylamide gel electrophoresis. A procedure for a partial purification of the extracellular enzyme to about 70-fold is presented.", "contents": "Multiple forms of an extracellular cyclic-AMP phosphodiesterase from Dictyostelium discoideum. The extracellular cyclic-AMP phosphodiesterase of a mutant of Dictyostelium discoideum which accumulates this enzyme was found to exist in multiple forms. Using the isoelectric focusing technique the phosphodiesterase activity was distributed into three peaks with isoelectric points of 4.6, 6.5 and 8.3, designated as p4, p6 and p8. Gel filtration and sucrose gradient analysis showed that the p4 activity consisted of two forms of different sedimentation coefficients. At high enzyme concentrations, the heavy form was favored. Dilution of enzyme activity shifted the equilibrium toward the light form. Direct analysis by sucrose gradient sedimentation of all isoelectric forms demonstrated that besides p4, p6 activity also existed as a mixture of the heavy (9.7 S) and the light (5.4 S) components. In contrast, the p8 activity displayed only the light form. The heterogeneity of the p4 and p6 isoelectric forms was also observed by polyacrylamide gel electrophoresis. A procedure for a partial purification of the extracellular enzyme to about 70-fold is presented."}
{"id": "PMID:222339", "title": "Collagenase, procollagenase and bone resorption. Effects of heparin, parathyroid hormone and calcitonin.", "content": "1. The addition of heparin to the culture fluid of mouse tibiae or calvaria did not cause any significant resorption of bone collagen or mineral. However, heparin (or analogue sulfated polyanions), enhanced greatly the amount of latent, trypsin-activatable collagenase (i.e. procollagenase) released by the bones in the medium without influencing that of directly active collagenase which was always very low. Heparin appeared to act by increasing the production of the enzyme which is immediately excreted. Procollagenase and collagenase are not stored in bone tissue, even under conditions where it is in active resorption. 2. Parathyroid hormone induced in the explants a resorption of both mineral and collagen that was inhibited by calcitonin. These hormones, however, had no influence on the release of procollagenase or collagenase either in the presence or in the absence of heparin. 3. Once activated, bone collagenase digested the collagen of the bone explants, and more extensively after their demineralization. Thus the latent collagenase that accumulates around non-resorbing bones has to be considered as a precursor, (and not as a residue), of active enzyme. 4. Active collagenase added to incipient cultures of bones disappeared with a half-life of 24 h. The lost enzyme could, however, not be reactivated by trypsin and thus was not transformed into latent procollagenase.", "contents": "Collagenase, procollagenase and bone resorption. Effects of heparin, parathyroid hormone and calcitonin. 1. The addition of heparin to the culture fluid of mouse tibiae or calvaria did not cause any significant resorption of bone collagen or mineral. However, heparin (or analogue sulfated polyanions), enhanced greatly the amount of latent, trypsin-activatable collagenase (i.e. procollagenase) released by the bones in the medium without influencing that of directly active collagenase which was always very low. Heparin appeared to act by increasing the production of the enzyme which is immediately excreted. Procollagenase and collagenase are not stored in bone tissue, even under conditions where it is in active resorption. 2. Parathyroid hormone induced in the explants a resorption of both mineral and collagen that was inhibited by calcitonin. These hormones, however, had no influence on the release of procollagenase or collagenase either in the presence or in the absence of heparin. 3. Once activated, bone collagenase digested the collagen of the bone explants, and more extensively after their demineralization. Thus the latent collagenase that accumulates around non-resorbing bones has to be considered as a precursor, (and not as a residue), of active enzyme. 4. Active collagenase added to incipient cultures of bones disappeared with a half-life of 24 h. The lost enzyme could, however, not be reactivated by trypsin and thus was not transformed into latent procollagenase."}
{"id": "PMID:222340", "title": "Gonadal receptors. I. Evidence for irreversibility in the binding of human chorionic gonadotropin and human luteinizing hormone.", "content": "The binding of human chorionic gonadotropin and human luteinizing hormone to particulate receptors of rat testes has generally been assumed to follow an equilibrium model similar to that proposed for many enzyme systems. Our work shows that equilibrium dissociation constant (Kd) and number of hormone binding sites (Bmax) are highly sensitive to changes in hormone and/or receptor concentration and to treatment received by tissue or receptor preparation prior to the assay. The results of binding assays obtained using receptor preparation pretreated with hormone (labeled as well as unlabeled) indicated that the binding reaction between hormone and receptor was irreversible and that pretreatment of the tissue with hormone greatly alters the number of high affinity gonadotropin binding sites in the testicular homogenate. Data from studies involving increasing receptor concentrations revealed that increasing the mass of particulate receptors in the binding assays leads to higher Kd as well as Bmax values. These findings are incompatible with a binding model based upon occupancy of receptor sites and the state of equilibrium implied. The incompatibilities are analyzed and an alternate model advanced (Bhalla, V.K., Trowbridge, C.G., Chen, C.J.H., Lindeman, J.G. and Rojas, F.J. (1979) Biochim. Biophys. Acta 584, 436--453).", "contents": "Gonadal receptors. I. Evidence for irreversibility in the binding of human chorionic gonadotropin and human luteinizing hormone. The binding of human chorionic gonadotropin and human luteinizing hormone to particulate receptors of rat testes has generally been assumed to follow an equilibrium model similar to that proposed for many enzyme systems. Our work shows that equilibrium dissociation constant (Kd) and number of hormone binding sites (Bmax) are highly sensitive to changes in hormone and/or receptor concentration and to treatment received by tissue or receptor preparation prior to the assay. The results of binding assays obtained using receptor preparation pretreated with hormone (labeled as well as unlabeled) indicated that the binding reaction between hormone and receptor was irreversible and that pretreatment of the tissue with hormone greatly alters the number of high affinity gonadotropin binding sites in the testicular homogenate. Data from studies involving increasing receptor concentrations revealed that increasing the mass of particulate receptors in the binding assays leads to higher Kd as well as Bmax values. These findings are incompatible with a binding model based upon occupancy of receptor sites and the state of equilibrium implied. The incompatibilities are analyzed and an alternate model advanced (Bhalla, V.K., Trowbridge, C.G., Chen, C.J.H., Lindeman, J.G. and Rojas, F.J. (1979) Biochim. Biophys. Acta 584, 436--453)."}
{"id": "PMID:222341", "title": "Gonadal receptors. II. Effects of time and reaction volume upon the binding of human chorionic gonadotropin and human luteinizing hormone to particulate receptors.", "content": "The effect of reaction volume upon the binding of gonadotropins by particulate receptors was studied. Two experimental approaches were used: one involved increasing the reaction volume of the binding assay (i.e. diluting the hormone and receptor concentrations and will be referred to as buffer coincubation studies) and the other involved incubating the testicular homogenate in various buffer volumes prior to the binding assay (buffer preincubation stidies). The results showed that the number of hormone binding sites inferred from Scatchard analysis was inversely related to the reaction volume in the coincubation as well as in the preincubation studies. Time-dependent dissociation of receptors from the intact testis was demonstrated by perifusion studies and the loss of receptors from intact testis correlated with the appearance of soluble factors (Bhalla, V.K., Haskell, J., Grier, H. and Mahesh, V.B. (1976) J. Biol. Chem. 251, 4947--4957) in the eluate obtained. The results obtained along with those presented in the preceding manuscript (Chen, C.J.H., Lindeman, J.G., Trowbridge, C.G. and Bhalla, V.K. (1979) Biochim. Biophys. Acta 284, 407--435) question the validity of the rapid equilibrium model which assumes reversible hormone occupancy of a fixed number of receptor sites. An alternate binding model is proposed herein and its implications are discussed.", "contents": "Gonadal receptors. II. Effects of time and reaction volume upon the binding of human chorionic gonadotropin and human luteinizing hormone to particulate receptors. The effect of reaction volume upon the binding of gonadotropins by particulate receptors was studied. Two experimental approaches were used: one involved increasing the reaction volume of the binding assay (i.e. diluting the hormone and receptor concentrations and will be referred to as buffer coincubation studies) and the other involved incubating the testicular homogenate in various buffer volumes prior to the binding assay (buffer preincubation stidies). The results showed that the number of hormone binding sites inferred from Scatchard analysis was inversely related to the reaction volume in the coincubation as well as in the preincubation studies. Time-dependent dissociation of receptors from the intact testis was demonstrated by perifusion studies and the loss of receptors from intact testis correlated with the appearance of soluble factors (Bhalla, V.K., Haskell, J., Grier, H. and Mahesh, V.B. (1976) J. Biol. Chem. 251, 4947--4957) in the eluate obtained. The results obtained along with those presented in the preceding manuscript (Chen, C.J.H., Lindeman, J.G., Trowbridge, C.G. and Bhalla, V.K. (1979) Biochim. Biophys. Acta 284, 407--435) question the validity of the rapid equilibrium model which assumes reversible hormone occupancy of a fixed number of receptor sites. An alternate binding model is proposed herein and its implications are discussed."}
{"id": "PMID:222342", "title": "Gonadotropin and prostaglandins binding sites in nuclei of bovine corpora lutea.", "content": "Highly purified nuclei isolated from bovine corpora lutea showed marked enrichment of NAD pyrophosphorylase, a marker for this organelle. Rough endoplasmic reticulum and lysosomal markers were undetectable, whereas plasma membrane and Golgi markers were detectable but not enriched in nuclei. These highly puridied nuclei exhibited specific binding with 125I-labeled human choriogonadotropin, [3H]prostaglandin E1 and [3H]prostaglandin F2 alpha. However, these bindings were only 15.4% (human choriogonadotropin), 7.9% (prostaglandin E1) and 8.9% (prostaglandin F2 alpha) of the plasma membrane binding observed under the same conditions. Washing of nuclei and plasma membranes twice with buffer containing 0.1% Triton X-100 resulted in gonadotropin and prostaglandin F2 alpha binding site and 5'-nucleotidase (EC 3.1.3.5) losses from nuclei that were different from those observed for plasma membranes. More importantly, the washed nuclei exhibited 44% (human choriogonadotropin), 21--26% (prostaglandins) of original specific binding despite virtual disappearance of 5'-nucleotidase activity. The nuclear membranes isolated from nuclei, specifically bound 125I-labeled human choriogonadotropin and [3H]prostaglandin F2 alpha to the same extent or significantly more ([3H]prostaglandin E1, P less than 0.05) than nuclei themselves, despite the marked losses of chromatin. In summary, our data suggest that gonadotropin and prostaglandins bind to nuclei and that this binding was intrinsic and was primarily associated with the nuclear membrane.", "contents": "Gonadotropin and prostaglandins binding sites in nuclei of bovine corpora lutea. Highly purified nuclei isolated from bovine corpora lutea showed marked enrichment of NAD pyrophosphorylase, a marker for this organelle. Rough endoplasmic reticulum and lysosomal markers were undetectable, whereas plasma membrane and Golgi markers were detectable but not enriched in nuclei. These highly puridied nuclei exhibited specific binding with 125I-labeled human choriogonadotropin, [3H]prostaglandin E1 and [3H]prostaglandin F2 alpha. However, these bindings were only 15.4% (human choriogonadotropin), 7.9% (prostaglandin E1) and 8.9% (prostaglandin F2 alpha) of the plasma membrane binding observed under the same conditions. Washing of nuclei and plasma membranes twice with buffer containing 0.1% Triton X-100 resulted in gonadotropin and prostaglandin F2 alpha binding site and 5'-nucleotidase (EC 3.1.3.5) losses from nuclei that were different from those observed for plasma membranes. More importantly, the washed nuclei exhibited 44% (human choriogonadotropin), 21--26% (prostaglandins) of original specific binding despite virtual disappearance of 5'-nucleotidase activity. The nuclear membranes isolated from nuclei, specifically bound 125I-labeled human choriogonadotropin and [3H]prostaglandin F2 alpha to the same extent or significantly more ([3H]prostaglandin E1, P less than 0.05) than nuclei themselves, despite the marked losses of chromatin. In summary, our data suggest that gonadotropin and prostaglandins bind to nuclei and that this binding was intrinsic and was primarily associated with the nuclear membrane."}
{"id": "PMID:222343", "title": "Binding of bovine parathyroid hormone to surface receptors of cultured B-lymphocytes.", "content": "Binding of parathyroid hormone onto B-lymphocytes is detected by the utilization of the labelled antibody membrane assay. The amount of parathyroid hormone bound to the receptor sites was depending on the quantity of cells in the incubation milieu. Each cell line showed typical characteristics in time course of parathyroid hormone binding and maximal receptor capacity. Fragmentation of intact parathyroid hormone, also varying with the cell line tested, was very rapid, even at 24 degrees C. Within 20 min most of the cell lines destroyed 20% of the native hormone in the incubation mixture, indicating a fragmentation rate of up to 2.25 ng/min at 37 degrees C. Bmax and KD for the different lymphocytes was 5.3--19 . 10(11) M and 1.8--18,5 . 10(11) M, respectively. These values are in the range of reported plasma concentrations and may therefore represent more physiological values for the capacity and affinity of membrane receptors.", "contents": "Binding of bovine parathyroid hormone to surface receptors of cultured B-lymphocytes. Binding of parathyroid hormone onto B-lymphocytes is detected by the utilization of the labelled antibody membrane assay. The amount of parathyroid hormone bound to the receptor sites was depending on the quantity of cells in the incubation milieu. Each cell line showed typical characteristics in time course of parathyroid hormone binding and maximal receptor capacity. Fragmentation of intact parathyroid hormone, also varying with the cell line tested, was very rapid, even at 24 degrees C. Within 20 min most of the cell lines destroyed 20% of the native hormone in the incubation mixture, indicating a fragmentation rate of up to 2.25 ng/min at 37 degrees C. Bmax and KD for the different lymphocytes was 5.3--19 . 10(11) M and 1.8--18,5 . 10(11) M, respectively. These values are in the range of reported plasma concentrations and may therefore represent more physiological values for the capacity and affinity of membrane receptors."}
{"id": "PMID:222344", "title": "Regulation of hydrogen utilisation in Rhizobium japonicum by cyclic AMP.", "content": "Utilisation (uptake) of hydrogen gas by whole cells of Rhizobium japonicum was found to be influenced by the carbon source(s) present in the growth medium, with activity being highest in a medium containing sugars. Tricarboxylic acid cycle intermediates, such as malate, significantly reduced H2 utilisation. No reduction in the hydrogenase activity is observed when the enzyme is assayed directly by the tritium exchange method, indicating that the decrease in hydrogen uptake activity is not due to repression of hydrogenase biosynthesis. Cyclic AMP was found to alleviate the inhibition of H2 uptake by malate, and this requires new protein synthesis. Addition of chloramphenicol or rifampicin simultaneously with cyclic AMP eliminated the stimulation of H2 uptake in the malate medium. These results show that in R. japonicum cyclic AMP plays a major role in the regulation of H2 metabolism.", "contents": "Regulation of hydrogen utilisation in Rhizobium japonicum by cyclic AMP. Utilisation (uptake) of hydrogen gas by whole cells of Rhizobium japonicum was found to be influenced by the carbon source(s) present in the growth medium, with activity being highest in a medium containing sugars. Tricarboxylic acid cycle intermediates, such as malate, significantly reduced H2 utilisation. No reduction in the hydrogenase activity is observed when the enzyme is assayed directly by the tritium exchange method, indicating that the decrease in hydrogen uptake activity is not due to repression of hydrogenase biosynthesis. Cyclic AMP was found to alleviate the inhibition of H2 uptake by malate, and this requires new protein synthesis. Addition of chloramphenicol or rifampicin simultaneously with cyclic AMP eliminated the stimulation of H2 uptake in the malate medium. These results show that in R. japonicum cyclic AMP plays a major role in the regulation of H2 metabolism."}
{"id": "PMID:222345", "title": "Synthesis of the calcium transport ATPase of sarcoplasmic reticulum and other muscle proteins during development of muscles cells in vivo and in vitro.", "content": "The effect of medium Ca2+ concentration upon the concentration and the rate of synthesis of muscle proteins was investigated in chicken pectoralis muscle cultures. There is an easily identifiable class of muscle protein which includes the Ca2+-ATPase of sarcoplasmic reticulum, myosin, troponin C, ATP : creatine phosphotransferase, muscle specific actin, tropomysin 1 and 2, and muscle hemagglutinin, which show a large increase in concentration during normal development. The increased synthesis of these proteins was inhibited, without inhibition of cell proliferation, in culture media of relatively low Ca2+ concentration, 0.05--0.3 mM, where fusion was prevented. Similar medium Ca2+ concentration was required for the expression of all these proteins, suggesting their coordinate regulation. The proteins are denoted as 'calcium-modulated proteins'. The increased Ca2+ transport activity of sarcoplasmic reticulum in cultured chicken pectoralis muscle cells during development at 1.8 mM medium calcium concentration represents de novo synthesis of the Ca2+ transport ATPase, as shown by immunoprecipitation, active site labeling and direct identification of the Ca2+ transport ATPase on two-dimensional gel electropherograms of whole muscle homogenates. The concentration and the turnover rate of the majority of the muscle proteins is not affected significantly by medium Ca2+ concentration between 0.06 and 1.8 mM. It is proposed that increase in cytoplasmic free Ca2+ concentration during fusion plays a central role in the regulation of the synthesis of calcium-modulated proteins.", "contents": "Synthesis of the calcium transport ATPase of sarcoplasmic reticulum and other muscle proteins during development of muscles cells in vivo and in vitro. The effect of medium Ca2+ concentration upon the concentration and the rate of synthesis of muscle proteins was investigated in chicken pectoralis muscle cultures. There is an easily identifiable class of muscle protein which includes the Ca2+-ATPase of sarcoplasmic reticulum, myosin, troponin C, ATP : creatine phosphotransferase, muscle specific actin, tropomysin 1 and 2, and muscle hemagglutinin, which show a large increase in concentration during normal development. The increased synthesis of these proteins was inhibited, without inhibition of cell proliferation, in culture media of relatively low Ca2+ concentration, 0.05--0.3 mM, where fusion was prevented. Similar medium Ca2+ concentration was required for the expression of all these proteins, suggesting their coordinate regulation. The proteins are denoted as 'calcium-modulated proteins'. The increased Ca2+ transport activity of sarcoplasmic reticulum in cultured chicken pectoralis muscle cells during development at 1.8 mM medium calcium concentration represents de novo synthesis of the Ca2+ transport ATPase, as shown by immunoprecipitation, active site labeling and direct identification of the Ca2+ transport ATPase on two-dimensional gel electropherograms of whole muscle homogenates. The concentration and the turnover rate of the majority of the muscle proteins is not affected significantly by medium Ca2+ concentration between 0.06 and 1.8 mM. It is proposed that increase in cytoplasmic free Ca2+ concentration during fusion plays a central role in the regulation of the synthesis of calcium-modulated proteins."}
{"id": "PMID:222346", "title": "Distribution and properties of protein kinase and protein phosphatase activities in synaptosomal plasma membranes and synaptic junctions.", "content": "Some characteristics of the protein kinase activity associated with a synaptosomal plasma membrane (synaptic membrane) fraction and a synaptic junction fraction have been compared. Autoradiography of the phosphorylated fractions separated on sodium dodecyl sulfate polyacrylamide gels showed that cyclic AMP stimulates the phosphorylation of five polypeptides in synaptic membranes, whereas no cyclic AMP dependency could be detected in synaptic junctions. Kinetic studies demonstrated that synaptic junctions contain a high Km and a low Km protein kinase activity while only the high Km activity could be detected in synaptic membranes. The intrinsic ATPase activity of synaptic membranes was shown to strongly interfere with measurements of protein kinase activity. Cyclic AMP binding experiments revealed a 2.6-fold enrichment of cyclic AMP binding capacity in synaptic junctions as compared to synaptic membranes. Protein phosphatase activity was not detected in synaptic junctions but was associated with synaptic membranes, where cyclic AMP was shown to either stimulate or inhibit the dephosphorylation of different polypeptides.", "contents": "Distribution and properties of protein kinase and protein phosphatase activities in synaptosomal plasma membranes and synaptic junctions. Some characteristics of the protein kinase activity associated with a synaptosomal plasma membrane (synaptic membrane) fraction and a synaptic junction fraction have been compared. Autoradiography of the phosphorylated fractions separated on sodium dodecyl sulfate polyacrylamide gels showed that cyclic AMP stimulates the phosphorylation of five polypeptides in synaptic membranes, whereas no cyclic AMP dependency could be detected in synaptic junctions. Kinetic studies demonstrated that synaptic junctions contain a high Km and a low Km protein kinase activity while only the high Km activity could be detected in synaptic membranes. The intrinsic ATPase activity of synaptic membranes was shown to strongly interfere with measurements of protein kinase activity. Cyclic AMP binding experiments revealed a 2.6-fold enrichment of cyclic AMP binding capacity in synaptic junctions as compared to synaptic membranes. Protein phosphatase activity was not detected in synaptic junctions but was associated with synaptic membranes, where cyclic AMP was shown to either stimulate or inhibit the dephosphorylation of different polypeptides."}
{"id": "PMID:222347", "title": "Characterization of the cyclic 3',5'-nucleotide phosphodiesterase actitivty associated with synaptosomal plasma membranes and synaptic junctions.", "content": "Some characteristics of the cyclic 3',5'-nucleotide phosphodiesterase (phosphodiesterase) activity associated with the synaptosomal plasma membrane (synaptic membrane) and the synaptic junction fractions of rat brain are reported. Kinetic analysis revealed that only one type of phosphodiesterase activity, with a Km of 2.10 19(-4) M for cyclic AMP, is associated with both fractions. The specific activities of the phosphodiesterase in synaptic membranes and synaptic junctions have been estimated at 23.4 nmol/min per mg protein and 22.5 nmol/min per mg protein, respectively. The synaptic junction-associated activity undergoes a 30% stimulation by Ca2+ while no Ca2+ sensitivity of the synaptic membrane-associated activity could be detected. Cytochemical studies performed on the synaptic membrane fraction demonstrated a predominant localization of phosphodiesterase activity over postsynaptic densities, while dense deposits were sometimes observed over the synaptic cleft region.", "contents": "Characterization of the cyclic 3',5'-nucleotide phosphodiesterase actitivty associated with synaptosomal plasma membranes and synaptic junctions. Some characteristics of the cyclic 3',5'-nucleotide phosphodiesterase (phosphodiesterase) activity associated with the synaptosomal plasma membrane (synaptic membrane) and the synaptic junction fractions of rat brain are reported. Kinetic analysis revealed that only one type of phosphodiesterase activity, with a Km of 2.10 19(-4) M for cyclic AMP, is associated with both fractions. The specific activities of the phosphodiesterase in synaptic membranes and synaptic junctions have been estimated at 23.4 nmol/min per mg protein and 22.5 nmol/min per mg protein, respectively. The synaptic junction-associated activity undergoes a 30% stimulation by Ca2+ while no Ca2+ sensitivity of the synaptic membrane-associated activity could be detected. Cytochemical studies performed on the synaptic membrane fraction demonstrated a predominant localization of phosphodiesterase activity over postsynaptic densities, while dense deposits were sometimes observed over the synaptic cleft region."}
{"id": "PMID:222348", "title": "Different effects of concanavalin A and its succinylated derivative on superoxide release in peritoneal macrophages.", "content": "The effects of tetravalent conconavalin A and its succinylated derivative on the intracellular production of superoxide anion (O-2) and its release into cell exterior of peritoneal macrophages were observed. Both tetravalent concanavalin A and its succinylated derivative induced marked enhancement of intracellular reduction of nitroblue tetrazolium, which could be inhibited by alpha-methyl-D-glucoside. The extent of activation of nitroblue tetrazolium reduction induced by both types of the lectin paralleled the activation ratio of oxygen consumption. There was little difference in the extent of intracellular O-2 production induced by two types of the lectin. Nitroblue tetrazolium reduction was not affected significantly by pretreatment with colchicine, rotenone or malonate, inhibitors of the cytoskeletal system and of the electron transport system. In contrast, tetravalent concanavalin A induced a higher rate of superoxide release than did succinylated divalent concanavalin A, which lacks the cross-linking activity of surface glycoproteins. These results indicate that superoxide production following oxygen consumption and superoxide release into cell exterior are controlled independently by a separate membrane mechanism and that superoxide production system is not essentially dependent on the involvement of the cytoskeletal system.", "contents": "Different effects of concanavalin A and its succinylated derivative on superoxide release in peritoneal macrophages. The effects of tetravalent conconavalin A and its succinylated derivative on the intracellular production of superoxide anion (O-2) and its release into cell exterior of peritoneal macrophages were observed. Both tetravalent concanavalin A and its succinylated derivative induced marked enhancement of intracellular reduction of nitroblue tetrazolium, which could be inhibited by alpha-methyl-D-glucoside. The extent of activation of nitroblue tetrazolium reduction induced by both types of the lectin paralleled the activation ratio of oxygen consumption. There was little difference in the extent of intracellular O-2 production induced by two types of the lectin. Nitroblue tetrazolium reduction was not affected significantly by pretreatment with colchicine, rotenone or malonate, inhibitors of the cytoskeletal system and of the electron transport system. In contrast, tetravalent concanavalin A induced a higher rate of superoxide release than did succinylated divalent concanavalin A, which lacks the cross-linking activity of surface glycoproteins. These results indicate that superoxide production following oxygen consumption and superoxide release into cell exterior are controlled independently by a separate membrane mechanism and that superoxide production system is not essentially dependent on the involvement of the cytoskeletal system."}
{"id": "PMID:222349", "title": "The effect of calcium on somatostatin inhibition of insulin release and cyclic AMP production in mouse pancreatic islets.", "content": "The effect of somatostatin on glucose-induced insulin secretion and cyclic AMP accumulation in isolated islets from obese, hyperglycemic ob/ob mice was studied in a microperifusion system. The normal biphasic pattern of insulin release as well as the inhibitory pattern of insulin release produced by somatostatin (0.5--1 microgram/ml) was matched by similar changes in the intracellular concentration of cyclic AMP. When islets were stimulated by glucose (3 mg/ml) plus 3-isobutyl-1-methylxanthine (0.1 mM), somatostatin (0.5 microgram/ml) failed to inhibit insulin secretion or cyclic AMP formation in the second phase whereas in the first phase both parameters were significantly reduced by somatostatin (0.5 microgram/ml). In batch-type incubations it was shown that addition of excess calcium (to 6 mM) reversed this inhibition. In the second phase calcium potentiated the (glucose + 3-isobutyl-1-methylxanthine)-stimulated insulin secretion without affecting the cyclic AMP production. This potentiation was inhibited by somatostatin (0.1 microgram/ml). Somatostatin (1 microgram/ml) inhibited adenylate cyclase activity in islet homogenates. No effect of somatostatin on islet glucose utilization could be demonstrated. The results indicate a dual action of somatostatin in the inhibition of insulin release, one involving the islet adenylate cyclase and one affecting the islet uptake of calcium.", "contents": "The effect of calcium on somatostatin inhibition of insulin release and cyclic AMP production in mouse pancreatic islets. The effect of somatostatin on glucose-induced insulin secretion and cyclic AMP accumulation in isolated islets from obese, hyperglycemic ob/ob mice was studied in a microperifusion system. The normal biphasic pattern of insulin release as well as the inhibitory pattern of insulin release produced by somatostatin (0.5--1 microgram/ml) was matched by similar changes in the intracellular concentration of cyclic AMP. When islets were stimulated by glucose (3 mg/ml) plus 3-isobutyl-1-methylxanthine (0.1 mM), somatostatin (0.5 microgram/ml) failed to inhibit insulin secretion or cyclic AMP formation in the second phase whereas in the first phase both parameters were significantly reduced by somatostatin (0.5 microgram/ml). In batch-type incubations it was shown that addition of excess calcium (to 6 mM) reversed this inhibition. In the second phase calcium potentiated the (glucose + 3-isobutyl-1-methylxanthine)-stimulated insulin secretion without affecting the cyclic AMP production. This potentiation was inhibited by somatostatin (0.1 microgram/ml). Somatostatin (1 microgram/ml) inhibited adenylate cyclase activity in islet homogenates. No effect of somatostatin on islet glucose utilization could be demonstrated. The results indicate a dual action of somatostatin in the inhibition of insulin release, one involving the islet adenylate cyclase and one affecting the islet uptake of calcium."}
{"id": "PMID:222350", "title": "Action of cholera toxin on dispersed acini from guinea pig pancreas.", "content": "In dispersed acini from guinea pig pancreas cholera toxin bound reversibly to specific membrane binding sites to increase cellular cyclic AMP and amylase secretion. Cholera toxin did not alter outflux of 45Ca or cellular cyclic AMP. Binding of 125I-labeled cholera toxin could be detected within 5 min; however, cholera toxin did not increase cyclic AMP or amylase release until after 40 min of incubation. There was a close correlation between the dose vs. response curve for inhibition of binding of 125I-labeled cholera toxin by native toxin and the action of native toxin on cellular cyclic AMP. With different concentrations of cholera toxin, maximal stimulation of amylase release occurred when the increase in cellular cyclic AMP was approximately 35% of maximal. Cholera toxin did not alter the increase in 45Ca outflux or cellular cyclic GMP caused by cholecystokinin or carbachol but significantly augmented the increase in cellular cyclic AMP caused by secretin or vasoactive intestinal peptide. The increase in amylase secretion caused by cholera toxin plus secretin or vasoactive intestinal peptide was the same as that with cholera toxin alone. On the other hand, the increase in amylase secretion caused by cholera toxin plus cholecystokinin or carbachol was significantly greater than the sum of the increases caused by each agent alone.", "contents": "Action of cholera toxin on dispersed acini from guinea pig pancreas. In dispersed acini from guinea pig pancreas cholera toxin bound reversibly to specific membrane binding sites to increase cellular cyclic AMP and amylase secretion. Cholera toxin did not alter outflux of 45Ca or cellular cyclic AMP. Binding of 125I-labeled cholera toxin could be detected within 5 min; however, cholera toxin did not increase cyclic AMP or amylase release until after 40 min of incubation. There was a close correlation between the dose vs. response curve for inhibition of binding of 125I-labeled cholera toxin by native toxin and the action of native toxin on cellular cyclic AMP. With different concentrations of cholera toxin, maximal stimulation of amylase release occurred when the increase in cellular cyclic AMP was approximately 35% of maximal. Cholera toxin did not alter the increase in 45Ca outflux or cellular cyclic GMP caused by cholecystokinin or carbachol but significantly augmented the increase in cellular cyclic AMP caused by secretin or vasoactive intestinal peptide. The increase in amylase secretion caused by cholera toxin plus secretin or vasoactive intestinal peptide was the same as that with cholera toxin alone. On the other hand, the increase in amylase secretion caused by cholera toxin plus cholecystokinin or carbachol was significantly greater than the sum of the increases caused by each agent alone."}
{"id": "PMID:222351", "title": "Dissociation by cooling of hormone and cholera toxin activation of adenylate cyclase in intact cells.", "content": "Cholera toxin, through adenylate cyclase activation reproduced cyclic AMP-mediated effects of thyroid-stimulating hormone (TSH) in dog thyroid slices, i.e. protein iodination, [1-14C]glucose-oxidation and hormone secretion. Iodide and carbamylcholine decreased the cyclic AMP accumulation induced by cholera toxin as well as by TSH, which supports the hypothesis of an action of these agents beyond the steps of hormone-receptor and receptor-adenylate cyclase interaction. Cooling to 20 degrees C did not impair the TSH induced cyclic AMP accumulation in thyroid slices, but completely suppressed the cholera toxin effect. This observation has been extended to other hormones and target tissues, such as the parathyroid hormone (PTH) (kidney cortex), adrenocorticotropic hormone (ACTH) (adrenal cortex) and luteinizing hormone (LH) (ovary systems). As in thyroid, cooling dissociated the cholera toxin and hormonal effects on cyclic AMP accumulation. In homogenate, cooling decreased cyclic AMP generation in the presence of cholera toxin but at 20 degrees C and 16 degrees C a cholera toxin stimulation was still observed. These results bear strongly against the hypothesis that the glycoprotein hormones TSH and LH acetivate adenylate cyclase by a mechanism identical to cholera toxin.", "contents": "Dissociation by cooling of hormone and cholera toxin activation of adenylate cyclase in intact cells. Cholera toxin, through adenylate cyclase activation reproduced cyclic AMP-mediated effects of thyroid-stimulating hormone (TSH) in dog thyroid slices, i.e. protein iodination, [1-14C]glucose-oxidation and hormone secretion. Iodide and carbamylcholine decreased the cyclic AMP accumulation induced by cholera toxin as well as by TSH, which supports the hypothesis of an action of these agents beyond the steps of hormone-receptor and receptor-adenylate cyclase interaction. Cooling to 20 degrees C did not impair the TSH induced cyclic AMP accumulation in thyroid slices, but completely suppressed the cholera toxin effect. This observation has been extended to other hormones and target tissues, such as the parathyroid hormone (PTH) (kidney cortex), adrenocorticotropic hormone (ACTH) (adrenal cortex) and luteinizing hormone (LH) (ovary systems). As in thyroid, cooling dissociated the cholera toxin and hormonal effects on cyclic AMP accumulation. In homogenate, cooling decreased cyclic AMP generation in the presence of cholera toxin but at 20 degrees C and 16 degrees C a cholera toxin stimulation was still observed. These results bear strongly against the hypothesis that the glycoprotein hormones TSH and LH acetivate adenylate cyclase by a mechanism identical to cholera toxin."}
{"id": "PMID:222352", "title": "The influence of fluoro-phenyl-alanine on the synthesis of simian virus 40 DNA and T antigens.", "content": "Treatment of Simian Virus 40 (SV40) infected monkey cells with fluorophenylalanine (FPA) resulted in increased uptake of thymidine by the cells, and progressive inhibition of both viral and cellular DNA synthesis. Viral DNA synthesis was more sensitive to inhibition by FPA than cell DNA synthesis. Synthesis of SV40 T antigens was however unaffected by FPA, as judged from immunofluorescence assays. The M.W. of the major polypetides immunoprecipitated from cell extracts by antibodies from tumor bearing hamster sera was similarly unaffected. It is suggested that T antigen synthesized in the presence of FPA is non functional.", "contents": "The influence of fluoro-phenyl-alanine on the synthesis of simian virus 40 DNA and T antigens. Treatment of Simian Virus 40 (SV40) infected monkey cells with fluorophenylalanine (FPA) resulted in increased uptake of thymidine by the cells, and progressive inhibition of both viral and cellular DNA synthesis. Viral DNA synthesis was more sensitive to inhibition by FPA than cell DNA synthesis. Synthesis of SV40 T antigens was however unaffected by FPA, as judged from immunofluorescence assays. The M.W. of the major polypetides immunoprecipitated from cell extracts by antibodies from tumor bearing hamster sera was similarly unaffected. It is suggested that T antigen synthesized in the presence of FPA is non functional."}
{"id": "PMID:222353", "title": "A theory on the control of arbitrary movements.", "content": "A theory dealing with the control of human, arbitrary movements is proposed. A schema is set up to suggest how the relevant information flows and what kind of operations affect it. A number of successive steps are distinguished in the production of a movement. It is assumed that the intended movement is carried out in the imagination, and that this imaginary movement is composed of a spatial trajectory and an intensity course, which are considered to be independent features of the intended movement. The spatial trajectory will be encoded in a special coding, which is related to the lengths of the muscles that effect the movement. From this special coding of the intended movement static and dynamic control signals can be derived. Because afferent and efferent signals are encoded in the same way in this schema, the evaluation and correction of the performed movement is quite simple. The higher levels in the control schema may function in an abstract way, i.e. the signals at these levels are barely concerned with details of the peripheral motor system. This abstract functioning of the higher levels is based on the numerous feedback mechanisms involved at all levels of control and in the peripheral motor system. Nevertheless, it is possible to incorporate specific peripheral properties in the generation of the control signals. The assumptions in this theory will be discussed and aspects of the proposed control schema will be compared with general control principles.", "contents": "A theory on the control of arbitrary movements. A theory dealing with the control of human, arbitrary movements is proposed. A schema is set up to suggest how the relevant information flows and what kind of operations affect it. A number of successive steps are distinguished in the production of a movement. It is assumed that the intended movement is carried out in the imagination, and that this imaginary movement is composed of a spatial trajectory and an intensity course, which are considered to be independent features of the intended movement. The spatial trajectory will be encoded in a special coding, which is related to the lengths of the muscles that effect the movement. From this special coding of the intended movement static and dynamic control signals can be derived. Because afferent and efferent signals are encoded in the same way in this schema, the evaluation and correction of the performed movement is quite simple. The higher levels in the control schema may function in an abstract way, i.e. the signals at these levels are barely concerned with details of the peripheral motor system. This abstract functioning of the higher levels is based on the numerous feedback mechanisms involved at all levels of control and in the peripheral motor system. Nevertheless, it is possible to incorporate specific peripheral properties in the generation of the control signals. The assumptions in this theory will be discussed and aspects of the proposed control schema will be compared with general control principles."}
{"id": "PMID:222354", "title": "Spatial firing patterns of auditory neuron network modelling by computer simulation.", "content": "This communication examines, in digital computer simulated network, input signals and response patterns established at excitatory neurons' level i.e. the membrane potential of neuron soma. It is restricted to spatial patterns of the auditory neuron networks and time factor for nervous conduction and transmission is neglected compared with long maintained membrane potentials of neuron somas. The model analyzes the change in the spatial patterns of the membrane potential in the two dimensional networks of the auditory system. In order to evaluate the contribution of the various parameters, it is started that the simplest model has only one parameter, lateral inhibition. The other parameters are then added, one at a time, to successive models. The lateral inhibition is a necessary condition in the auditory nervous system if any sharpening of the response areas in the single neurons is to occur. A necessary condition for the validity of the model is that is should be applicable to the other senses such as vision and chemical patterns, taste. The threshold feature of auditory neurons aids in producing a sharpening in the neuron of the auditory relay nuclei. It does this clipping the spatial response patterns in one dimensional arrays of excitatory neurons. Recurrent inhibition seems a necessary condition in the sensory nervous system that any kinds of input signals are to be preserved over a wide range of stimulus intensity. In other words, this network has a wide dynamic range against any kinds of input signals. A simple self-recurrent negative feedback does not contribute to the sharpening, but more complex socalled averaged type does. A neuron network is capable of responding stably to stimuli with a wide range of intensity and with any kind of spatial patterns if there is a simple negative feedback mechanism. When there is no negative feedback, input signals soon disappear or saturate in the neuron network. Therefore, recurrent inhibition is the most important mechanism. Spontaneous activity appears to aid in the sharpening by providing a kind of contrast, that is by reducting the amount of activity in neurons adjacent to the excitatory area. Moreover, the effect of spontaneous activity in the model seems to make repples around the excitatory area and suggests that an introduction of activity at any stage of the networks, from whatever source for example reticulum formation and thalamus, might appreciably alter the response patterns at subsequent neuron network. This suggests that the mechanism of the consciousness that might be controlled by the thalamus and or reticular formation. These two dimensional neuron networks may be expanded to three dimensional neuron networks. The former might simulate the auditory nervous system while the latter might simulate the visual system.", "contents": "Spatial firing patterns of auditory neuron network modelling by computer simulation. This communication examines, in digital computer simulated network, input signals and response patterns established at excitatory neurons' level i.e. the membrane potential of neuron soma. It is restricted to spatial patterns of the auditory neuron networks and time factor for nervous conduction and transmission is neglected compared with long maintained membrane potentials of neuron somas. The model analyzes the change in the spatial patterns of the membrane potential in the two dimensional networks of the auditory system. In order to evaluate the contribution of the various parameters, it is started that the simplest model has only one parameter, lateral inhibition. The other parameters are then added, one at a time, to successive models. The lateral inhibition is a necessary condition in the auditory nervous system if any sharpening of the response areas in the single neurons is to occur. A necessary condition for the validity of the model is that is should be applicable to the other senses such as vision and chemical patterns, taste. The threshold feature of auditory neurons aids in producing a sharpening in the neuron of the auditory relay nuclei. It does this clipping the spatial response patterns in one dimensional arrays of excitatory neurons. Recurrent inhibition seems a necessary condition in the sensory nervous system that any kinds of input signals are to be preserved over a wide range of stimulus intensity. In other words, this network has a wide dynamic range against any kinds of input signals. A simple self-recurrent negative feedback does not contribute to the sharpening, but more complex socalled averaged type does. A neuron network is capable of responding stably to stimuli with a wide range of intensity and with any kind of spatial patterns if there is a simple negative feedback mechanism. When there is no negative feedback, input signals soon disappear or saturate in the neuron network. Therefore, recurrent inhibition is the most important mechanism. Spontaneous activity appears to aid in the sharpening by providing a kind of contrast, that is by reducting the amount of activity in neurons adjacent to the excitatory area. Moreover, the effect of spontaneous activity in the model seems to make repples around the excitatory area and suggests that an introduction of activity at any stage of the networks, from whatever source for example reticulum formation and thalamus, might appreciably alter the response patterns at subsequent neuron network. This suggests that the mechanism of the consciousness that might be controlled by the thalamus and or reticular formation. These two dimensional neuron networks may be expanded to three dimensional neuron networks. The former might simulate the auditory nervous system while the latter might simulate the visual system."}
{"id": "PMID:222355", "title": "A theory for the acquisition and loss of neuron specificity in visual cortex.", "content": "We assume that between lateral geniculate and visual cortical cells there exist labile synapses that modify themselves in a new fashion called threshold passive modification and in addition, non-labile synapses that contain permanent information. In the theory which results there is an increase in the specificity of response of a cortical cell when it is exposed to stimuli due to normal patterned visual experience. Non-patterned input, such as might be expected when an animal is dark-reared or raised with eyelids sutured, results in a loss of specificity, with details depending on whether noise to labile and non-labile junctions is correlated. Specificity can sometimes be regained, however, with a return of input due to patterned vision. We propose that this provides a possible explanation of experimental results obtained by Imbert and Buisseret (1975); Blakemore and Van Sluyters (1975); Buisseret and Imbert (1976); and Fr\u00e9gnac and Imbert (1977, 1978).", "contents": "A theory for the acquisition and loss of neuron specificity in visual cortex. We assume that between lateral geniculate and visual cortical cells there exist labile synapses that modify themselves in a new fashion called threshold passive modification and in addition, non-labile synapses that contain permanent information. In the theory which results there is an increase in the specificity of response of a cortical cell when it is exposed to stimuli due to normal patterned visual experience. Non-patterned input, such as might be expected when an animal is dark-reared or raised with eyelids sutured, results in a loss of specificity, with details depending on whether noise to labile and non-labile junctions is correlated. Specificity can sometimes be regained, however, with a return of input due to patterned vision. We propose that this provides a possible explanation of experimental results obtained by Imbert and Buisseret (1975); Blakemore and Van Sluyters (1975); Buisseret and Imbert (1976); and Fr\u00e9gnac and Imbert (1977, 1978)."}
{"id": "PMID:222356", "title": "[Distribution of carbonic anhydrase, K+-ATPase and K+-phosphatase in subcellular fractions of gastric mucosa].", "content": "The distribution of carbonic anhydrase, K+-ATPase and K+-phosphatase in the subcellular fractions of gastric mucosa was studied. It was found that 90% of carbonic anhydrase are localized in the hyaloplasm, whereas K+-ATPase and K+-phosphatase are predominantly localized in the microsomal fraction. Subfractionation of the microsomal fraction in a sucrose density gradient showed that the membrane-bound carbonic anhydrase (5% of total content) and K+-ATPase are bound to various cell organelles. It is concluded that carbonic anhydrase functions as an intracellular pH-stat and is not directly involved in proton generation by the cell.", "contents": "[Distribution of carbonic anhydrase, K+-ATPase and K+-phosphatase in subcellular fractions of gastric mucosa]. The distribution of carbonic anhydrase, K+-ATPase and K+-phosphatase in the subcellular fractions of gastric mucosa was studied. It was found that 90% of carbonic anhydrase are localized in the hyaloplasm, whereas K+-ATPase and K+-phosphatase are predominantly localized in the microsomal fraction. Subfractionation of the microsomal fraction in a sucrose density gradient showed that the membrane-bound carbonic anhydrase (5% of total content) and K+-ATPase are bound to various cell organelles. It is concluded that carbonic anhydrase functions as an intracellular pH-stat and is not directly involved in proton generation by the cell."}
{"id": "PMID:222357", "title": "[Interaction of inorganic anions with copper atoms of cytochrome oxidase].", "content": "The effects of cyanide, thiocyanide, azide, nitrite, nitrate, ferricyanide, persulfate, sulfide and halogenides on the intensities of the EPR spectrum and the band of 825 nm of cardiac cutochrome oxidase were studied. It was shown that according to their action on the copper the anions may be classified into three groups: 1) anions inducing the reduction of the copper (CN-, CNS-, S2-) anions changing the environment of the copper (N3-, NO2-); 3) anions slightly interacting with the copper (NO3-, halogenides). The incubation of cytochrome oxidase with ferricyanide led to the formation of a free-radical component without causing any pronounced changes in the copper environment; however, treatment of the protein with persulfate was accompanied by an irreversible modification of the copper EPR spectrum.", "contents": "[Interaction of inorganic anions with copper atoms of cytochrome oxidase]. The effects of cyanide, thiocyanide, azide, nitrite, nitrate, ferricyanide, persulfate, sulfide and halogenides on the intensities of the EPR spectrum and the band of 825 nm of cardiac cutochrome oxidase were studied. It was shown that according to their action on the copper the anions may be classified into three groups: 1) anions inducing the reduction of the copper (CN-, CNS-, S2-) anions changing the environment of the copper (N3-, NO2-); 3) anions slightly interacting with the copper (NO3-, halogenides). The incubation of cytochrome oxidase with ferricyanide led to the formation of a free-radical component without causing any pronounced changes in the copper environment; however, treatment of the protein with persulfate was accompanied by an irreversible modification of the copper EPR spectrum."}
{"id": "PMID:222358", "title": "[Interaction between the dexamethasone-receptor complex and Zajdela ascites hepatoma DNA].", "content": "The activated dexamethasone--receptor complex from rat liver cell cytoplasm and from Zajdela ascite hepatoma cell cytoplasm is bound to Sepharose-immobilized native DNA containing different numbers of recurrent sequences. The DNA-bound hormonereceptor complex is eluted as three peaks by varying concentrations of NaCl. The binding in independent of the number of DNA recurrent sequences and of the source of the cytoplasmic complex used.", "contents": "[Interaction between the dexamethasone-receptor complex and Zajdela ascites hepatoma DNA]. The activated dexamethasone--receptor complex from rat liver cell cytoplasm and from Zajdela ascite hepatoma cell cytoplasm is bound to Sepharose-immobilized native DNA containing different numbers of recurrent sequences. The DNA-bound hormonereceptor complex is eluted as three peaks by varying concentrations of NaCl. The binding in independent of the number of DNA recurrent sequences and of the source of the cytoplasmic complex used."}
{"id": "PMID:222359", "title": "[Isolation and structural properties of membrane-bound Na+,K+- adenosine triphosphatase from pig kidney].", "content": "A technique for isolation of large amounts of homogeneous Na+, K+-ATPase lipid-protein complex from pig kindney has been developed. The purity of the preparation as determined by the protein component is 96-98%, the large to small subparticle ratio being 4 : 1. The protein and lipid parts of the preparation have approximately the same mass. The enzyme activity is 1600-1900 mcmoles of inorganic phosphate released per mg of protein per hour. The protein secondary structure in a heavy water solution has been studied by infrared spectroscopy in the region of the main amide bands. It has been shown that about 20% of the peptide groups form highly ordered alpha-helical regions and about 25% are found in the pleated sheet structure with an antiparallel packing of the chains. The regions with a regular structure are mainly located in the protein component regions, inaccessible for water and are presumably involved in the formation of the hydrophobic core of the molecule. The major part of the protein structure (approximately 55%) is non-ordered and is easily accessible for water molecules.", "contents": "[Isolation and structural properties of membrane-bound Na+,K+- adenosine triphosphatase from pig kidney]. A technique for isolation of large amounts of homogeneous Na+, K+-ATPase lipid-protein complex from pig kindney has been developed. The purity of the preparation as determined by the protein component is 96-98%, the large to small subparticle ratio being 4 : 1. The protein and lipid parts of the preparation have approximately the same mass. The enzyme activity is 1600-1900 mcmoles of inorganic phosphate released per mg of protein per hour. The protein secondary structure in a heavy water solution has been studied by infrared spectroscopy in the region of the main amide bands. It has been shown that about 20% of the peptide groups form highly ordered alpha-helical regions and about 25% are found in the pleated sheet structure with an antiparallel packing of the chains. The regions with a regular structure are mainly located in the protein component regions, inaccessible for water and are presumably involved in the formation of the hydrophobic core of the molecule. The major part of the protein structure (approximately 55%) is non-ordered and is easily accessible for water molecules."}
{"id": "PMID:222374", "title": "Prediciting the clinical success of restorative dental materials.", "content": "This paper discusses dental restorative resins, alloys, cements and implants and emphasizes the need for useful laboratory information that will predict the clinical behavior of these materials and structures.", "contents": "Prediciting the clinical success of restorative dental materials. This paper discusses dental restorative resins, alloys, cements and implants and emphasizes the need for useful laboratory information that will predict the clinical behavior of these materials and structures."}
{"id": "PMID:222377", "title": "[Changes in the Na, K-ATPase of neuronal membranes in penicillin-induced epileptic foci in the cerebral cortex of the rat].", "content": "The relationship between electrophysiological changes and Na, K-ATPase activity of neuronal membranes in sodium penicillin-induced epileptic foci was studied. Na,K-ATPase activity is inhibited both in the primary focus and in homotopic contralateral area during latent period and in the stage of forming epileptic activity. In the stage of marked convulsive activity Na, K-ATPase is inhibited only in the primary focus. It is shown that penicillin at a concentration range of 2 x 10(-6)--2 x 10(-3) M does not influence Na,K-ATPase activity of crude synaptosomes of the rat brain cortex. It is suggested that Na,K-ATPase inactivation may serve as a pathogenetic factor in the development of convulsive process.", "contents": "[Changes in the Na, K-ATPase of neuronal membranes in penicillin-induced epileptic foci in the cerebral cortex of the rat]. The relationship between electrophysiological changes and Na, K-ATPase activity of neuronal membranes in sodium penicillin-induced epileptic foci was studied. Na,K-ATPase activity is inhibited both in the primary focus and in homotopic contralateral area during latent period and in the stage of forming epileptic activity. In the stage of marked convulsive activity Na, K-ATPase is inhibited only in the primary focus. It is shown that penicillin at a concentration range of 2 x 10(-6)--2 x 10(-3) M does not influence Na,K-ATPase activity of crude synaptosomes of the rat brain cortex. It is suggested that Na,K-ATPase inactivation may serve as a pathogenetic factor in the development of convulsive process."}
{"id": "PMID:222378", "title": "[Cytotoxic antibodies against tumor cells in the blood of intact C3H mice].", "content": "Cytotoxic antibodies against mouse mammary tumour cells, L-cells and hepatoma 22a cells have been found in the serum of C3H/f and C3H/He mice over 8 months of age. Analogues antibodies were found in the serum of young and old BALB/c mice, but not in C57BL/6 mice. The cytotoxic activity of antimammary tumour cell serum has been completely abolished by its depletion by renal tissue of syngeneic and allogeneic animals.", "contents": "[Cytotoxic antibodies against tumor cells in the blood of intact C3H mice]. Cytotoxic antibodies against mouse mammary tumour cells, L-cells and hepatoma 22a cells have been found in the serum of C3H/f and C3H/He mice over 8 months of age. Analogues antibodies were found in the serum of young and old BALB/c mice, but not in C57BL/6 mice. The cytotoxic activity of antimammary tumour cell serum has been completely abolished by its depletion by renal tissue of syngeneic and allogeneic animals."}
{"id": "PMID:222379", "title": "[Horseradish peroxidase-labeled cells as sources of the spinoreticular and spinothalamic systems of the brain].", "content": "The cells of spinoreticular and spinothalamic fibrous systems of the cat brain were studied by the method of axone transmission of horse-radish peroxidase (HP). A dense accumulation of HP-labeled neurons establishing direct relations with the reticular formation and thalamus was seen in the upper segments of the spinal cord. In the lower segments these zones were confined to the medial part of the ventral horn and the intermediate zone of the gray matter. The neurons established direct connections with contralateral nuclei of the reticular formation as well as with the thalamus ipsi- and contralateral nuclei. Possible pathways of transmitting somatic and pain sensitivity are discussed.", "contents": "[Horseradish peroxidase-labeled cells as sources of the spinoreticular and spinothalamic systems of the brain]. The cells of spinoreticular and spinothalamic fibrous systems of the cat brain were studied by the method of axone transmission of horse-radish peroxidase (HP). A dense accumulation of HP-labeled neurons establishing direct relations with the reticular formation and thalamus was seen in the upper segments of the spinal cord. In the lower segments these zones were confined to the medial part of the ventral horn and the intermediate zone of the gray matter. The neurons established direct connections with contralateral nuclei of the reticular formation as well as with the thalamus ipsi- and contralateral nuclei. Possible pathways of transmitting somatic and pain sensitivity are discussed."}
{"id": "PMID:222384", "title": "Acetylcholine receptors in the ciliary ganglion and in the iris muscle of the chick: specific binding and effect on the synaptic transmission of the neurotoxin from Naja naja siamensis.", "content": "1 A specific binding of Naja naja siamensis neurotoxin was found both in the iris and in the ciliary ganglion of the chick. 2 Naja-toxin (125 nM) caused a complete block of the iris muscle contraction induced by carbamylcholine. 3 Naja-toxin had a different effect on the two neuronal populations present in the ganglion: it blocked the synaptically evoked response of the ciliary cells, while the response of the choroid ones was only slightly reduced. The effects were the same in a wide range of concentrations (125 to 2500 nM). 4 The results obtained in the iris show the existence of an acetylcholine receptor population similar to the nicotinic receptor of the skeletal muscle. 5 In the ciliary ganglion the results confirm the existence of different acetylcholine receptors on the two cell types.", "contents": "Acetylcholine receptors in the ciliary ganglion and in the iris muscle of the chick: specific binding and effect on the synaptic transmission of the neurotoxin from Naja naja siamensis. 1 A specific binding of Naja naja siamensis neurotoxin was found both in the iris and in the ciliary ganglion of the chick. 2 Naja-toxin (125 nM) caused a complete block of the iris muscle contraction induced by carbamylcholine. 3 Naja-toxin had a different effect on the two neuronal populations present in the ganglion: it blocked the synaptically evoked response of the ciliary cells, while the response of the choroid ones was only slightly reduced. The effects were the same in a wide range of concentrations (125 to 2500 nM). 4 The results obtained in the iris show the existence of an acetylcholine receptor population similar to the nicotinic receptor of the skeletal muscle. 5 In the ciliary ganglion the results confirm the existence of different acetylcholine receptors on the two cell types."}
{"id": "PMID:222385", "title": "An analysis of some factors influencing alpha-adrenoceptor feed-back at the sympathetic junction in the rat heart.", "content": "1 The effects of the selective prejunctional alpha-adrenoceptor antagonist, yohimbine, on the cardioacceleration responses to sympathetic stimulation were examined in the pithed rat. 2 Yohimbine reversed the inhibitory effects of the alpha-adrenoceptor agonist, clonidine, on the stimulation-induced tachycardia. 3 Yohimbine failed to potentiate significantly responses to stimulation in the absence of clonidine when stimulation was applied at the optimal level for cardiac responses (C6-T1). 4 When the pithing rod electrode was moved to T2-T6, cardioaccelerator responses were smaller and yohimbine produced potentiation at frequencies of greater than or equal to 1 Hz. This potentiation was prejunctional since responses to exogenous noradrenaline (NA) were not increased by yohimbine. 5 In the presence of cocaine, potentiation by yohimbine could be shown at the lower frequency of 0.1 Hz. 6 The possible physiological significance of a negative feed-back effect of noradrenaline on cardiac sympathetic nerves is discussed.", "contents": "An analysis of some factors influencing alpha-adrenoceptor feed-back at the sympathetic junction in the rat heart. 1 The effects of the selective prejunctional alpha-adrenoceptor antagonist, yohimbine, on the cardioacceleration responses to sympathetic stimulation were examined in the pithed rat. 2 Yohimbine reversed the inhibitory effects of the alpha-adrenoceptor agonist, clonidine, on the stimulation-induced tachycardia. 3 Yohimbine failed to potentiate significantly responses to stimulation in the absence of clonidine when stimulation was applied at the optimal level for cardiac responses (C6-T1). 4 When the pithing rod electrode was moved to T2-T6, cardioaccelerator responses were smaller and yohimbine produced potentiation at frequencies of greater than or equal to 1 Hz. This potentiation was prejunctional since responses to exogenous noradrenaline (NA) were not increased by yohimbine. 5 In the presence of cocaine, potentiation by yohimbine could be shown at the lower frequency of 0.1 Hz. 6 The possible physiological significance of a negative feed-back effect of noradrenaline on cardiac sympathetic nerves is discussed."}
{"id": "PMID:222390", "title": "Spontaneous and traumatic rupture of hepatoma.", "content": "Hepatoma is a common cause of spontaneous rupture of the liver. During recent years, spontaneous rupture was found in 11 (7 per cent) of 157 patients with hepatoma. The rupture occurred spontaneously in 7 patients, traumatically in 1 while in 3 patients trivial trauma seemed to be the precipitating factor. A correct preoperative diagnosis was made in 7 patients, all of whom were known to have a hepatoma. Hepatic resection was performed in 4 patients, 2 of whom were long term survivors. Haemorrhage stopped in 2 of 3 patients who underwent hepatic artery ligation, but only 1 patient was discharged from hospital. The remaining patients, who were treated by packing, suture or laparotomy alone, died within a short time after admission. It is suggested that resection is the preferred management, but if this is not possible hepatic artery ligation should be performed.", "contents": "Spontaneous and traumatic rupture of hepatoma. Hepatoma is a common cause of spontaneous rupture of the liver. During recent years, spontaneous rupture was found in 11 (7 per cent) of 157 patients with hepatoma. The rupture occurred spontaneously in 7 patients, traumatically in 1 while in 3 patients trivial trauma seemed to be the precipitating factor. A correct preoperative diagnosis was made in 7 patients, all of whom were known to have a hepatoma. Hepatic resection was performed in 4 patients, 2 of whom were long term survivors. Haemorrhage stopped in 2 of 3 patients who underwent hepatic artery ligation, but only 1 patient was discharged from hospital. The remaining patients, who were treated by packing, suture or laparotomy alone, died within a short time after admission. It is suggested that resection is the preferred management, but if this is not possible hepatic artery ligation should be performed."}
{"id": "PMID:222392", "title": "Effect of cholera toxin and prostaglandins on the rat choroid plexus in vitro.", "content": "The present study was performed to measure the effects of cholera toxin (CT) and prostaglandins (PG) on choroid plexus cyclic AMP accumulation. Choroid plexuses, isolated from Sprague-Dawley rats, were incubated in Krebs-Ringer bicarbonate buffer containing either CT (10 microgram/ml), heat inactivated CT, prostaglandins, or appropriate controls. After a minimum incubation period of 60 min with CT, cyclic AMP accumulation (pmol/mg protein) in treated incubates (58.10 +/- 6.43, n = 6) was 4 times that in controls (14.-5 +/- 1.4, n = 6). This large increase was only seen when theophylline (10 mM) was in the incubation mixture 3--10 min prior to the end of the incubation period. The increase in cyclic AMP accumulation was dose responsive and was irreversible after 5 min of incubation. Of the 5 prostaglandins studied, only PGE2 resulted in an increase in cyclic AMP accumulation. Cyclic AMP levels were 29.64 +/- 2.5 in controls and 57.57 +/- 3.5 in plexus which had been incubated with PGE2 (20 microgram/ml) for 1 min, and this increase was dose responsive.", "contents": "Effect of cholera toxin and prostaglandins on the rat choroid plexus in vitro. The present study was performed to measure the effects of cholera toxin (CT) and prostaglandins (PG) on choroid plexus cyclic AMP accumulation. Choroid plexuses, isolated from Sprague-Dawley rats, were incubated in Krebs-Ringer bicarbonate buffer containing either CT (10 microgram/ml), heat inactivated CT, prostaglandins, or appropriate controls. After a minimum incubation period of 60 min with CT, cyclic AMP accumulation (pmol/mg protein) in treated incubates (58.10 +/- 6.43, n = 6) was 4 times that in controls (14.-5 +/- 1.4, n = 6). This large increase was only seen when theophylline (10 mM) was in the incubation mixture 3--10 min prior to the end of the incubation period. The increase in cyclic AMP accumulation was dose responsive and was irreversible after 5 min of incubation. Of the 5 prostaglandins studied, only PGE2 resulted in an increase in cyclic AMP accumulation. Cyclic AMP levels were 29.64 +/- 2.5 in controls and 57.57 +/- 3.5 in plexus which had been incubated with PGE2 (20 microgram/ml) for 1 min, and this increase was dose responsive."}
{"id": "PMID:222394", "title": "The effects of methionine- and leucine-enkephalin on spinal neurones of the cat.", "content": "Extra- and intracellular recordings were obtained from physiologically identified, spinal neurones in the 6th and 7th lumbar segments of the pentobarbitone-anaesthetized cat. Microiontophoretically applied methionine- and leucine-enkephalin reversibly inhibited the spontaneous, synaptically induced, and L-glutamate-induced activity in the majority of dorsal horn neurones studied in laminae 4, 5 and 6 of Rexed. Most of these depressant effects were antagonized by the prior microiontophoretic application of the opiate antagonist naloxone. Intracellular studies performed on dorsal horn neurones and motoneurones revealed that microiontophoretically applied methionine- and leucine-enkephalin caused no change in the resting membrane potential or the membrane resistance. Neither spike initiation nor spike overshoot were detectably altered by either enkephalin. The membrane depolarization and associated decrease in membrane resistance following microiontophoretic L-glutamate application were effectively blocked by the prior application of enkephalin. Naloxone, which by itself had no detectable effect on the membrane resistance, antagonized this effect. We propose that [enkephalinergic] cells in lamina II and III may modulate cells subserving somatosensory perception, including pain.", "contents": "The effects of methionine- and leucine-enkephalin on spinal neurones of the cat. Extra- and intracellular recordings were obtained from physiologically identified, spinal neurones in the 6th and 7th lumbar segments of the pentobarbitone-anaesthetized cat. Microiontophoretically applied methionine- and leucine-enkephalin reversibly inhibited the spontaneous, synaptically induced, and L-glutamate-induced activity in the majority of dorsal horn neurones studied in laminae 4, 5 and 6 of Rexed. Most of these depressant effects were antagonized by the prior microiontophoretic application of the opiate antagonist naloxone. Intracellular studies performed on dorsal horn neurones and motoneurones revealed that microiontophoretically applied methionine- and leucine-enkephalin caused no change in the resting membrane potential or the membrane resistance. Neither spike initiation nor spike overshoot were detectably altered by either enkephalin. The membrane depolarization and associated decrease in membrane resistance following microiontophoretic L-glutamate application were effectively blocked by the prior application of enkephalin. Naloxone, which by itself had no detectable effect on the membrane resistance, antagonized this effect. We propose that [enkephalinergic] cells in lamina II and III may modulate cells subserving somatosensory perception, including pain."}
{"id": "PMID:222396", "title": "The relationship between extracellular calcium concentrations and the induction of hippocampal long-term potentiation.", "content": "The effect of varying calcium and magnesium concentrations was observed on the development of long-term potentiation (LTP) in the CA1 region of the rat hippocampus maintained in vitro. Treatments which would be expected to lower the depolarization-induced influx of calcium into neuronal elements (i.e. lowering Ca2+ or raising Mg2+ in the perfusion medium) selectively antagonized LTP, while synaptic transmission, paired-pulse and frequency facilitation, as well as short-term (or post-tetanic) potentiation were all maintained. This suggests that LTP is unrelated to these short-term forms of plasticity, but is either a calcium-dependent process itself, or is dependent upon some other calcium-related phenomenon (such as transmitter release).", "contents": "The relationship between extracellular calcium concentrations and the induction of hippocampal long-term potentiation. The effect of varying calcium and magnesium concentrations was observed on the development of long-term potentiation (LTP) in the CA1 region of the rat hippocampus maintained in vitro. Treatments which would be expected to lower the depolarization-induced influx of calcium into neuronal elements (i.e. lowering Ca2+ or raising Mg2+ in the perfusion medium) selectively antagonized LTP, while synaptic transmission, paired-pulse and frequency facilitation, as well as short-term (or post-tetanic) potentiation were all maintained. This suggests that LTP is unrelated to these short-term forms of plasticity, but is either a calcium-dependent process itself, or is dependent upon some other calcium-related phenomenon (such as transmitter release)."}
{"id": "PMID:222398", "title": "The isolation and lipid composition of subcellular fractions derived from neuronal perikarya isolated in bulk from rabbit cerebral cortex.", "content": "(1) Neuronal perikarya were isolated from rabbit cerebral cortex and were homogenized and separated into a number of subcellular membrane fractions using differential and discontinuous density gradient centrifugation. (2) The efficiency of homogenizing the nerve cell bodies could be greatly increased by the preliminary passage of the cell body fraction through a micropipet tip. (3) Of a number of density media, a discontinuous gradient of metrizamide gave the best resolution of the mitochondrial and lysosomal marker enzymes found in the crude mitochondrial fraction. This yielded a purified mitochondrial fraction and several lighter membrane fractions. (4) The lighter membrane fractions in metrizamide contained a degree of mitochondrial contamination which could be removed by a second gradient spin on 1.2 M sucrose, producing a second mitochondrial fraction and two light membrane fractions. (5) Based on marker analyses, fractions enriched in nuclei, mitochondria, microsomes and plasma membrane/lysosomes were produced. (6) The two mitochondrial fractions showed the highest, and the nuclear fraction the lowest specific phospholipid content. Cholesterol: phospholipid molar ratios showed a gradient of values from a low (0.2) for the mitochondria and nuclei to an intermediate value (0.4) for the microsomes to a high (0.6) for the light membrane fractions. (7) Phospholipid distributions indicated that for the nuclear and mitochondrial fractions phosphatidylinositol was more abundant than sphingomyelin or phosphatidylserine, while for the microsomes and the two light membrane fractions these three phospholipids were present in almost equal amounts.", "contents": "The isolation and lipid composition of subcellular fractions derived from neuronal perikarya isolated in bulk from rabbit cerebral cortex. (1) Neuronal perikarya were isolated from rabbit cerebral cortex and were homogenized and separated into a number of subcellular membrane fractions using differential and discontinuous density gradient centrifugation. (2) The efficiency of homogenizing the nerve cell bodies could be greatly increased by the preliminary passage of the cell body fraction through a micropipet tip. (3) Of a number of density media, a discontinuous gradient of metrizamide gave the best resolution of the mitochondrial and lysosomal marker enzymes found in the crude mitochondrial fraction. This yielded a purified mitochondrial fraction and several lighter membrane fractions. (4) The lighter membrane fractions in metrizamide contained a degree of mitochondrial contamination which could be removed by a second gradient spin on 1.2 M sucrose, producing a second mitochondrial fraction and two light membrane fractions. (5) Based on marker analyses, fractions enriched in nuclei, mitochondria, microsomes and plasma membrane/lysosomes were produced. (6) The two mitochondrial fractions showed the highest, and the nuclear fraction the lowest specific phospholipid content. Cholesterol: phospholipid molar ratios showed a gradient of values from a low (0.2) for the mitochondria and nuclei to an intermediate value (0.4) for the microsomes to a high (0.6) for the light membrane fractions. (7) Phospholipid distributions indicated that for the nuclear and mitochondrial fractions phosphatidylinositol was more abundant than sphingomyelin or phosphatidylserine, while for the microsomes and the two light membrane fractions these three phospholipids were present in almost equal amounts."}
{"id": "PMID:222399", "title": "The antagonism of amino acid-induced excitation of spinal neurones in the cat.", "content": "DL-alpha-Aminoadipate (DLalphaAA) and L-glutamic acid diethylester (GDEE) were compared as antagonists of the excitatory effects of a number of amino acids on interneurones, and also of acetylcholine on Renshaw cells of the cat spinal cord. The excitants could be ranked in order of their sensitivity of the two antagonists. Ibotenate and the optical isomers of N-methylaspartate were the most readily antagonised by DLalphaAA and the least by GDEE; L-glutamate and quisqualate were most affected by GDEE and least by DLalphaAA; the actions of L-cysteate, L-aspartate and D- and L-homocysteate were reduced to some extent by both; and kainate was relatively insensitive to both antagonists. Acetylcholine excitations of Renshaw cells were often reduced by GDEE and occasionally by DLalphaAA. The results indicate the existence on spinal neurones of at least two populations of amino acid receptors which have differing sensitivities to the antagonists, and which do not precisely conform to the \"glutamate-perferring\" and \"aspartate-preferring\" categories which have been proposed on other grounds.", "contents": "The antagonism of amino acid-induced excitation of spinal neurones in the cat. DL-alpha-Aminoadipate (DLalphaAA) and L-glutamic acid diethylester (GDEE) were compared as antagonists of the excitatory effects of a number of amino acids on interneurones, and also of acetylcholine on Renshaw cells of the cat spinal cord. The excitants could be ranked in order of their sensitivity of the two antagonists. Ibotenate and the optical isomers of N-methylaspartate were the most readily antagonised by DLalphaAA and the least by GDEE; L-glutamate and quisqualate were most affected by GDEE and least by DLalphaAA; the actions of L-cysteate, L-aspartate and D- and L-homocysteate were reduced to some extent by both; and kainate was relatively insensitive to both antagonists. Acetylcholine excitations of Renshaw cells were often reduced by GDEE and occasionally by DLalphaAA. The results indicate the existence on spinal neurones of at least two populations of amino acid receptors which have differing sensitivities to the antagonists, and which do not precisely conform to the \"glutamate-perferring\" and \"aspartate-preferring\" categories which have been proposed on other grounds."}
{"id": "PMID:222405", "title": "Effect of lithium on parathyroid hormone-induced calcium release from bone rudiments.", "content": "Lithium treatment of humans and animals has been associated with adverse effects on bone and mineral metabolism. In order to determine whether lithium was altering the skeletal response to parathyroid hormone, we incubated bone rudiments for 5 days in the presence or absence of the drugs. Lithium had no effect on either parathyroid hormone-induced cyclic AMP generation or 45Ca release from the bone rudiments. The data are consistent with the hypothesis that the skeletal effects of lithium are not mediated via inhibition of the parathyroid hormone-adenyl cyclase-cyclic AMP system.", "contents": "Effect of lithium on parathyroid hormone-induced calcium release from bone rudiments. Lithium treatment of humans and animals has been associated with adverse effects on bone and mineral metabolism. In order to determine whether lithium was altering the skeletal response to parathyroid hormone, we incubated bone rudiments for 5 days in the presence or absence of the drugs. Lithium had no effect on either parathyroid hormone-induced cyclic AMP generation or 45Ca release from the bone rudiments. The data are consistent with the hypothesis that the skeletal effects of lithium are not mediated via inhibition of the parathyroid hormone-adenyl cyclase-cyclic AMP system."}
{"id": "PMID:222406", "title": "Structural studies of staphylococcal protease. III. Binding of anions to the spin-labeled enzyme.", "content": "The staphylococcal protease was coupled at the active-site serine residue with a spin-labeled analog of diisopropyl fluorophosphonate and the interaction of competitive inhibitors such as chloride and acetate anions, as well as N-carbobenzoxy-L-glutamic acid (Z-L-Glu), was investigated by electron paramagnetic resonance spectroscopy. It was observed that the addition of chloride ions to the spin-labeled enzyme increased the freedom of motion of the spin label while the presence of acetate ions and Z-L-Glu resulted in an increase in the immobilization of the spin label. These results suggest that these ions bind to the active site region in different ways.", "contents": "Structural studies of staphylococcal protease. III. Binding of anions to the spin-labeled enzyme. The staphylococcal protease was coupled at the active-site serine residue with a spin-labeled analog of diisopropyl fluorophosphonate and the interaction of competitive inhibitors such as chloride and acetate anions, as well as N-carbobenzoxy-L-glutamic acid (Z-L-Glu), was investigated by electron paramagnetic resonance spectroscopy. It was observed that the addition of chloride ions to the spin-labeled enzyme increased the freedom of motion of the spin label while the presence of acetate ions and Z-L-Glu resulted in an increase in the immobilization of the spin label. These results suggest that these ions bind to the active site region in different ways."}
{"id": "PMID:222408", "title": "The interactions of adenylates with allosteric citrate synthase.", "content": "Evidence is presented that a number of derivatives of adenylic acid may bind to the allosteric NADH binding site of Escherichia coli citrate synthase. This evidence includes the facts that all the adenylates inhibit NADH binding in a competitive manner and that those which have been tested protect an enzyme sulfhydryl group from reaction with 5,5'-dithiobis-(2-nitrobenzoic acid) in the same way that NADH does. However, whereas NADH is a potent inhibitor of citrate synthase, most of the adenylates are activators. The best activator, ADP-ribose, increases the affinity of the enzyme for the substrate, acetyl-CoA, and saturates the enzyme in a sigmoid manner. A fluorescence technique, involving the displacement of 8-anilino-1-naphthalenesulfonate from its complex with citrate synthase, is used to obtain saturation curves for several nucleotides under nonassay conditions. It is found that acetyl-coenzyme A, coenzyme A, and ADP-ribose all bind to the enzyme cooperatively, and that the binding of each becomes tighter in the presence of KCl, the activator, and oxaloacetic acid (OAA), the second substrate. Another inhibitor, alpha-ketoglutarate, can complete with OAA in the absence of KCl but not in its presence. The nature of the allosteric site of citrate synthase, and the modes of action of several activators and inhibitors, are discussed in the light of this evidence.", "contents": "The interactions of adenylates with allosteric citrate synthase. Evidence is presented that a number of derivatives of adenylic acid may bind to the allosteric NADH binding site of Escherichia coli citrate synthase. This evidence includes the facts that all the adenylates inhibit NADH binding in a competitive manner and that those which have been tested protect an enzyme sulfhydryl group from reaction with 5,5'-dithiobis-(2-nitrobenzoic acid) in the same way that NADH does. However, whereas NADH is a potent inhibitor of citrate synthase, most of the adenylates are activators. The best activator, ADP-ribose, increases the affinity of the enzyme for the substrate, acetyl-CoA, and saturates the enzyme in a sigmoid manner. A fluorescence technique, involving the displacement of 8-anilino-1-naphthalenesulfonate from its complex with citrate synthase, is used to obtain saturation curves for several nucleotides under nonassay conditions. It is found that acetyl-coenzyme A, coenzyme A, and ADP-ribose all bind to the enzyme cooperatively, and that the binding of each becomes tighter in the presence of KCl, the activator, and oxaloacetic acid (OAA), the second substrate. Another inhibitor, alpha-ketoglutarate, can complete with OAA in the absence of KCl but not in its presence. The nature of the allosteric site of citrate synthase, and the modes of action of several activators and inhibitors, are discussed in the light of this evidence."}
{"id": "PMID:222411", "title": "Diazepam potentiation of purinergic depression of central neurons.", "content": "Intravenously or iontophoretically applied diazepam potentiated the depressant action of iontophoretically applied 5'-AMP on the spontaneous firing of rat cerebral cortical neurons. This potentiation of purinergic depression may be a result of the previously reported inhibition by diazepam of uptake of adenosine into brain tissues.", "contents": "Diazepam potentiation of purinergic depression of central neurons. Intravenously or iontophoretically applied diazepam potentiated the depressant action of iontophoretically applied 5'-AMP on the spontaneous firing of rat cerebral cortical neurons. This potentiation of purinergic depression may be a result of the previously reported inhibition by diazepam of uptake of adenosine into brain tissues."}
{"id": "PMID:222417", "title": "Isolation and characterisation of guanine auxotrophs in Saccharomyces cerevisiae.", "content": "Mutants of yeast which are auxotrophic for guanine have been isolated from two prototrophic haploid strains, one of which carried the suppressor of purine excretion, su-pur, and the other carried the alternative allele, su-pur+. The mutants were allocated to three genes, gual, gua2, and gua3, between which no close linkage was demonstrable. Mutants of all three genes were recessive and showed normal Mendelian segregation in crosses. The gene gual was shown by an in vivo enzyme assay procedure to specify guanosine 5'-phosphate (GMP) synthetase, the second enzyme involved in the biosynthesis of GMP from inosine 5'-phosphate (IMP). Mutants of this gene excrete large amounts of purine derivatives, predominantly xanthosine, into guanine-free, but not into guanine-supplemented, medium. The gene gau2 is probably involved in the biosynthesis of riboflavin from guanine nucleotides; the phenotype of these mutants suggests a possible interaction between aromatic amino acid metabolism and riboflavin biosynthesis. No role for gua3 can be assigned on the evidence so far available, but it is not involved in the specification of IMP dehydrogenase, the first enzyme involved in the synthesis of GMP and IMP.", "contents": "Isolation and characterisation of guanine auxotrophs in Saccharomyces cerevisiae. Mutants of yeast which are auxotrophic for guanine have been isolated from two prototrophic haploid strains, one of which carried the suppressor of purine excretion, su-pur, and the other carried the alternative allele, su-pur+. The mutants were allocated to three genes, gual, gua2, and gua3, between which no close linkage was demonstrable. Mutants of all three genes were recessive and showed normal Mendelian segregation in crosses. The gene gual was shown by an in vivo enzyme assay procedure to specify guanosine 5'-phosphate (GMP) synthetase, the second enzyme involved in the biosynthesis of GMP from inosine 5'-phosphate (IMP). Mutants of this gene excrete large amounts of purine derivatives, predominantly xanthosine, into guanine-free, but not into guanine-supplemented, medium. The gene gau2 is probably involved in the biosynthesis of riboflavin from guanine nucleotides; the phenotype of these mutants suggests a possible interaction between aromatic amino acid metabolism and riboflavin biosynthesis. No role for gua3 can be assigned on the evidence so far available, but it is not involved in the specification of IMP dehydrogenase, the first enzyme involved in the synthesis of GMP and IMP."}
{"id": "PMID:222418", "title": "Abdominal crisis due to metastasizing lung carcinoma to the small bowel.", "content": "A rare case of small-bowel perforation due to metastasizing primary bronchogenic carcinoma is reported. A 64-year-old man presented with acute abdominal crisis from perforation of a metastatic focus in the wall of the small intestine. A 13-cm segment of small bowel, containing a firm mass which surrounded a 1.0 X 2.0-cm perforation, was resected. Because of widespread metastases, the patient received only palliative treatment. He died 27 days after admission. Perforation of a metastatic focus in the small bowel is considered a late complication of carcinoma and indicates a very poor prognosis. This is only the eighth reported case of such a complication of metastasizing lung carcinoma.", "contents": "Abdominal crisis due to metastasizing lung carcinoma to the small bowel. A rare case of small-bowel perforation due to metastasizing primary bronchogenic carcinoma is reported. A 64-year-old man presented with acute abdominal crisis from perforation of a metastatic focus in the wall of the small intestine. A 13-cm segment of small bowel, containing a firm mass which surrounded a 1.0 X 2.0-cm perforation, was resected. Because of widespread metastases, the patient received only palliative treatment. He died 27 days after admission. Perforation of a metastatic focus in the small bowel is considered a late complication of carcinoma and indicates a very poor prognosis. This is only the eighth reported case of such a complication of metastasizing lung carcinoma."}
{"id": "PMID:222419", "title": "Recurrent obstipation as a complication of partial pancreatectomy for non-beta cell adenoma of the pancreas.", "content": "Verner and Morrison, in 1958, reported non-insulin-secreting tumours of the pancreas that were associated with a syndrome of refractory diarrhea, achlorhydria and hypokalemia. Surgical resection of such tumours results in rebound acid hypersecretion and cessation of the watery diarrhea. The authors report the case of an 84-year-old man who had three of the four major criteria for diagnosis of the Verner Morrison syndrome. Hypokalemia was absent, but this was possibly due to the large doses of potassium chloride that he was taking in conjunction with diuretics. After resection of the tumour severe obstipation with resultant bowel obstruction developed in addition to rebound hypersecretion and relief of watery diarrhea. Treatment, consisting of bulk laxatives in appropriate amounts, alleviated the obstipation.", "contents": "Recurrent obstipation as a complication of partial pancreatectomy for non-beta cell adenoma of the pancreas. Verner and Morrison, in 1958, reported non-insulin-secreting tumours of the pancreas that were associated with a syndrome of refractory diarrhea, achlorhydria and hypokalemia. Surgical resection of such tumours results in rebound acid hypersecretion and cessation of the watery diarrhea. The authors report the case of an 84-year-old man who had three of the four major criteria for diagnosis of the Verner Morrison syndrome. Hypokalemia was absent, but this was possibly due to the large doses of potassium chloride that he was taking in conjunction with diuretics. After resection of the tumour severe obstipation with resultant bowel obstruction developed in addition to rebound hypersecretion and relief of watery diarrhea. Treatment, consisting of bulk laxatives in appropriate amounts, alleviated the obstipation."}
{"id": "PMID:222420", "title": "Mammography: a surgeon's experience.", "content": "Most reports advocating mammography have been written by radiologists rather than by clinicians who are frequently confronted by women with breast complaints. The value of mammography in managing patients with breast problems was studied by reviewing its role in 1026 breast consultations; there were 129 patients with cancer. Mammography was performed in 95 patients. The procedure hastened the diagnosis of one comedocarcinoma, and in another patient was suspicious 3 years before she presented with a locally advanced lesion. It missed six cancers. In seven patients it recognized clinically obvious cancers, though in one of these it had given negative results 10 months before the patient presented with a lesion 15 cm in diameter. It also falsely suggested the possibility of cancer in 28 women. In the other 52 patients the clinical diagnosis of a benign condition was usually fairly evident. The morbidity caused by mammography does not seem to have been widely appreciated, no doubt because of the hope that clinically unrecognized cancers would be found by it. Most breast problems can be diagnosed without mammography.", "contents": "Mammography: a surgeon's experience. Most reports advocating mammography have been written by radiologists rather than by clinicians who are frequently confronted by women with breast complaints. The value of mammography in managing patients with breast problems was studied by reviewing its role in 1026 breast consultations; there were 129 patients with cancer. Mammography was performed in 95 patients. The procedure hastened the diagnosis of one comedocarcinoma, and in another patient was suspicious 3 years before she presented with a locally advanced lesion. It missed six cancers. In seven patients it recognized clinically obvious cancers, though in one of these it had given negative results 10 months before the patient presented with a lesion 15 cm in diameter. It also falsely suggested the possibility of cancer in 28 women. In the other 52 patients the clinical diagnosis of a benign condition was usually fairly evident. The morbidity caused by mammography does not seem to have been widely appreciated, no doubt because of the hope that clinically unrecognized cancers would be found by it. Most breast problems can be diagnosed without mammography."}
{"id": "PMID:222421", "title": "Anaplastic astrocytoma following radiation for a glomus jugular tumor.", "content": "Evaluation of radiation therapy for a given neoplasm includes consideration of possible treatment complications as well as potential benefit. A 43-year-old male with a glomus jugular tumor or the right middle ear had received 4480 rad to the right middle and inner ear and temporal bone. Eight years later, he developed an anaplastic astrocytoma of the right cerebellar hemisphere. At this time a third neoplasm, a left carotid body tumor, was demonstrated angiographically. Although radiation can be implicated in the genesis of the glial neoplasm, the presence of two neural crest derived tumors suggests that a lowered threshold for neoplastic transformation in neuroectodermal cells may have been an additional factor. Long-term follow-up of large numbers of patients with glomus jugulare tumors will be necessary to determine if multiple paragangliomas predispose to radiation-associated gliomas.", "contents": "Anaplastic astrocytoma following radiation for a glomus jugular tumor. Evaluation of radiation therapy for a given neoplasm includes consideration of possible treatment complications as well as potential benefit. A 43-year-old male with a glomus jugular tumor or the right middle ear had received 4480 rad to the right middle and inner ear and temporal bone. Eight years later, he developed an anaplastic astrocytoma of the right cerebellar hemisphere. At this time a third neoplasm, a left carotid body tumor, was demonstrated angiographically. Although radiation can be implicated in the genesis of the glial neoplasm, the presence of two neural crest derived tumors suggests that a lowered threshold for neoplastic transformation in neuroectodermal cells may have been an additional factor. Long-term follow-up of large numbers of patients with glomus jugulare tumors will be necessary to determine if multiple paragangliomas predispose to radiation-associated gliomas."}
{"id": "PMID:222422", "title": "ACTH-secreting carcinoma of the breast.", "content": "We report a case of ACTH-secreting carcinoma of the breast. Membrane-bound secretory granules were seen within the cancer cells electron microscopically. Cytoplasmic granules reacting immunochemically to anti-ACTH antisera were seen on light microscopy. Breast cancers have been shown to secrete calcitonin, parathyroid hormone, human chorionic gonadotropin, and norepinephrine in addition to ACTH. This suggests either the presence of neuroendocrine cells in the breast as a source of such neoplasms, as in the lung, or genomic derepression during neoplastic transformation.", "contents": "ACTH-secreting carcinoma of the breast. We report a case of ACTH-secreting carcinoma of the breast. Membrane-bound secretory granules were seen within the cancer cells electron microscopically. Cytoplasmic granules reacting immunochemically to anti-ACTH antisera were seen on light microscopy. Breast cancers have been shown to secrete calcitonin, parathyroid hormone, human chorionic gonadotropin, and norepinephrine in addition to ACTH. This suggests either the presence of neuroendocrine cells in the breast as a source of such neoplasms, as in the lung, or genomic derepression during neoplastic transformation."}
{"id": "PMID:222423", "title": "Electron spin resonance studies on properties of ceruloplasmin and transferrin in blood from normal human subjects and cancer patients.", "content": "The methodology of blood sample preparation and analysis has been examined to further evaluate the technique of electron spin resonance (ESR) for possible use in detecting cancer and in monitoring the progress of cancer therapy. Frozen whole blood and serum samples from 278 normal donors and 97 cancer patients were studied by ESR for signal intensity from Cu+2 bound to ceruloplasmin (g factor = 2.05). The signal from this species (Cu+2-CP) in serum rose sharply during the first two hours of storage at room temperature after being drawn from the subject, and then reached a plateau. The average Cu+2-CP ESR signal intensity was significantly different for control groups of males, females not taking estrogen medication, and females taking estrogens. The mean ESR signal intensities of Cu+2-CP from cancer patients separated into the same groups as the control data were approximately twice as great as the mean control levels. Total serum copper levels were correlated with ESR intensities of Cu+2-CP and indicated that the ratio of Cu+2/Cu+1 in CP is higher in serum from cancer patients than from controls.", "contents": "Electron spin resonance studies on properties of ceruloplasmin and transferrin in blood from normal human subjects and cancer patients. The methodology of blood sample preparation and analysis has been examined to further evaluate the technique of electron spin resonance (ESR) for possible use in detecting cancer and in monitoring the progress of cancer therapy. Frozen whole blood and serum samples from 278 normal donors and 97 cancer patients were studied by ESR for signal intensity from Cu+2 bound to ceruloplasmin (g factor = 2.05). The signal from this species (Cu+2-CP) in serum rose sharply during the first two hours of storage at room temperature after being drawn from the subject, and then reached a plateau. The average Cu+2-CP ESR signal intensity was significantly different for control groups of males, females not taking estrogen medication, and females taking estrogens. The mean ESR signal intensities of Cu+2-CP from cancer patients separated into the same groups as the control data were approximately twice as great as the mean control levels. Total serum copper levels were correlated with ESR intensities of Cu+2-CP and indicated that the ratio of Cu+2/Cu+1 in CP is higher in serum from cancer patients than from controls."}
{"id": "PMID:222424", "title": "Acute leukemia with unusual cytoplasmic inclusions: a cytochemical and ultrastructural study.", "content": "A 76-year-old woman with acute leukemia responded incompletely to prednisone and vincristine. Cytochemistry of the blast cells demonstrated only focal alpha-naphthyl acetate and alpha-naphthyl butyrate esterase activity and focal coarse granular beta-glucuronidase activity, a pattern usually associated with acute lymphocytic leukemia. Electron microscopy demonstrated primitive cells with features usually associated with promonocyte differentiation including prominent parallel arrays of microfilaments and nucleoli of the nucleolonema type. In Wright-stained films, blasts contained oval, pale-blue, yellow tinged cytoplasmic inclusions about 2 to 4 micrometers in diameter which did not stain with any of the cytochemical methods employed. With electron microscopy, these inclusions were nonmembrane bound structures, varying from amorphous electron dense stippling to irregularly arranged short segments of filaments to prominent parallel arrays of filaments. We propose that the inclusions may have arisen from the parallel arrays of microfilaments and are nonspecific.", "contents": "Acute leukemia with unusual cytoplasmic inclusions: a cytochemical and ultrastructural study. A 76-year-old woman with acute leukemia responded incompletely to prednisone and vincristine. Cytochemistry of the blast cells demonstrated only focal alpha-naphthyl acetate and alpha-naphthyl butyrate esterase activity and focal coarse granular beta-glucuronidase activity, a pattern usually associated with acute lymphocytic leukemia. Electron microscopy demonstrated primitive cells with features usually associated with promonocyte differentiation including prominent parallel arrays of microfilaments and nucleoli of the nucleolonema type. In Wright-stained films, blasts contained oval, pale-blue, yellow tinged cytoplasmic inclusions about 2 to 4 micrometers in diameter which did not stain with any of the cytochemical methods employed. With electron microscopy, these inclusions were nonmembrane bound structures, varying from amorphous electron dense stippling to irregularly arranged short segments of filaments to prominent parallel arrays of filaments. We propose that the inclusions may have arisen from the parallel arrays of microfilaments and are nonspecific."}
{"id": "PMID:222425", "title": "Multiple-hormone producing lung carcinoma.", "content": "Endocrine and immunohistochemical studies were performed in a patient with lung cancer associated with gynecomastia. Elevated level of human chorionic gonadotropin (hCG) in plasma and mild hyperadrenocorticism were demonstrated by hormone assays. Postmortem examination proved the existence of anaplastic small cell carcinoma of the lung mixed with a feature of chorioepithelioma. The presence of significant amounts of adrenocorticotropic hormone (ACTH), beta-melanocyte stimulating hormone (beta-MSH), calcitonin, gastrin, hCG, hCG-alpha, hCG-beta and human chorionic somatomammotropin (hCS) in tumor tissues was demonstrated by radioimmunoassays, bioassay and immunohistochemical techniques. We present here a unique case of multiple hormones producing tumor elaborating both hormones of amine precursor uptake and decarboxylation (APUD) series (ACTH, beta-MSH, calcitonin and gastrin) and of placental origin (hCG, hCG-alpha, hCG-beta and hCS).", "contents": "Multiple-hormone producing lung carcinoma. Endocrine and immunohistochemical studies were performed in a patient with lung cancer associated with gynecomastia. Elevated level of human chorionic gonadotropin (hCG) in plasma and mild hyperadrenocorticism were demonstrated by hormone assays. Postmortem examination proved the existence of anaplastic small cell carcinoma of the lung mixed with a feature of chorioepithelioma. The presence of significant amounts of adrenocorticotropic hormone (ACTH), beta-melanocyte stimulating hormone (beta-MSH), calcitonin, gastrin, hCG, hCG-alpha, hCG-beta and human chorionic somatomammotropin (hCS) in tumor tissues was demonstrated by radioimmunoassays, bioassay and immunohistochemical techniques. We present here a unique case of multiple hormones producing tumor elaborating both hormones of amine precursor uptake and decarboxylation (APUD) series (ACTH, beta-MSH, calcitonin and gastrin) and of placental origin (hCG, hCG-alpha, hCG-beta and hCS)."}
{"id": "PMID:222426", "title": "Malignant small cell tumor of the thoracopulmonary region in childhood: a distinctive clinicopathologic entity of uncertain histogenesis.", "content": "This report describes a unique clinicopathologic entity characterized as a malignant small cell tumor of the thoracopulmonary region in 20 children and adolescents (average age 14.5 years). There was a female predilection (75%) for this tumor which appeared to originate in the soft tissues of the chest wall or the peripheral lung. The neoplasm tended to recur locally and did not seem to disseminate as widely as some of the other small cell tumors of childhood (rhabdomyosarcoma, Ewing's sarcoma, neuroblastoma and malignant lymphoma). However, the median survival was only 8 months. Electron microscopy of 3 cases suggested a neuroepithelial derivation, but, at the present, the histogeneis remains a subject for further investigation.", "contents": "Malignant small cell tumor of the thoracopulmonary region in childhood: a distinctive clinicopathologic entity of uncertain histogenesis. This report describes a unique clinicopathologic entity characterized as a malignant small cell tumor of the thoracopulmonary region in 20 children and adolescents (average age 14.5 years). There was a female predilection (75%) for this tumor which appeared to originate in the soft tissues of the chest wall or the peripheral lung. The neoplasm tended to recur locally and did not seem to disseminate as widely as some of the other small cell tumors of childhood (rhabdomyosarcoma, Ewing's sarcoma, neuroblastoma and malignant lymphoma). However, the median survival was only 8 months. Electron microscopy of 3 cases suggested a neuroepithelial derivation, but, at the present, the histogeneis remains a subject for further investigation."}
{"id": "PMID:222427", "title": "Primary adenoid cystic carcinoma of the esophagus: report of a case.", "content": "A case of primary adenoid cystic carcinoma of the esophagus is reported. A 51-year-old male patient had a tumor in the lower third of the esophagus which was incidentally found during an examination for cholelithiasis, and resected successfully. The tumor exhibited a polypoid appearance covered by normal esophageal epithelium, localized entirely in the submucosal layer, and morphologically identical to adenoid cystic carcinoma in the salivary glands. The patient is still alive and well three and one-half years after surgery. This seems to be a typical case of adenoid cystic carcinoma of the esophagus arising from the submucosal esophageal gland.", "contents": "Primary adenoid cystic carcinoma of the esophagus: report of a case. A case of primary adenoid cystic carcinoma of the esophagus is reported. A 51-year-old male patient had a tumor in the lower third of the esophagus which was incidentally found during an examination for cholelithiasis, and resected successfully. The tumor exhibited a polypoid appearance covered by normal esophageal epithelium, localized entirely in the submucosal layer, and morphologically identical to adenoid cystic carcinoma in the salivary glands. The patient is still alive and well three and one-half years after surgery. This seems to be a typical case of adenoid cystic carcinoma of the esophagus arising from the submucosal esophageal gland."}
{"id": "PMID:222428", "title": "Cancer cell estrogen receptor of human mammary carcinoma.", "content": "Estrogen receptor level expressed as percentages of estrogen receptor-positive cancer cells in the infiltrating cancer cell populations was analyzed with a fluorescent estradiol histochemical technique in fifty-two primary infiltrating and metastatic human mammary carcinomas. The estrogen receptor-positive cancer cells equaled or exceeded the estrogen receptor-negative in number in twelve tumors (23%). The remaining (77%) tumors contained largely estrogen receptor-negative cancer cells. Comparison of the estrogen receptor value in the cytosol derived from tumor tissue homogenates with the histochemical finding in forty cases failed to obtain parallel correlation. Noninvasive intraductal carcinomas were found to be consistently composed of estrogen receptor-negative cancer cells even when present in the vicinity of foci of infiltrating cancer cells with high estrogen receptor activity. In contrast, benign intraductal hyperplastic lesions and papillomas were frequently characterized by piling up of estrogen receptor-positive epithelial cells in the mammary ducts. These observations suggest that when malignant transformation takes place, the cancer cells lose most or all of the progenitors' ability to synthesize estrogen receptors during the intraductal stage of proliferation. This ability is only regained, if ever, by some of the cancer cells during the subsequent infiltrating phase in the stroma. Only occasionally, proliferation of the estrogen receptor-positive cancer cells becomes a prevailing tendency in a human mammary cancer.", "contents": "Cancer cell estrogen receptor of human mammary carcinoma. Estrogen receptor level expressed as percentages of estrogen receptor-positive cancer cells in the infiltrating cancer cell populations was analyzed with a fluorescent estradiol histochemical technique in fifty-two primary infiltrating and metastatic human mammary carcinomas. The estrogen receptor-positive cancer cells equaled or exceeded the estrogen receptor-negative in number in twelve tumors (23%). The remaining (77%) tumors contained largely estrogen receptor-negative cancer cells. Comparison of the estrogen receptor value in the cytosol derived from tumor tissue homogenates with the histochemical finding in forty cases failed to obtain parallel correlation. Noninvasive intraductal carcinomas were found to be consistently composed of estrogen receptor-negative cancer cells even when present in the vicinity of foci of infiltrating cancer cells with high estrogen receptor activity. In contrast, benign intraductal hyperplastic lesions and papillomas were frequently characterized by piling up of estrogen receptor-positive epithelial cells in the mammary ducts. These observations suggest that when malignant transformation takes place, the cancer cells lose most or all of the progenitors' ability to synthesize estrogen receptors during the intraductal stage of proliferation. This ability is only regained, if ever, by some of the cancer cells during the subsequent infiltrating phase in the stroma. Only occasionally, proliferation of the estrogen receptor-positive cancer cells becomes a prevailing tendency in a human mammary cancer."}
{"id": "PMID:222429", "title": "Electron microscopic findings in primitive neuroectodermal tumors of the cerebrum.", "content": "The fine structure of 3 primitive neuroectodermal neoplasms of the cerebral hemispheres was studied. The predominant tumor cells were undifferentiated cells with prominent nuclei and scanty cytoplasm containing few organelles. Ultrastructural evidence suggesting differentiation into ependymal, neuronal and possibly astrocytic elements was also present. This study suggests that the cell of origin of this tumor is a primitive multipotential cell of the cerebrum.", "contents": "Electron microscopic findings in primitive neuroectodermal tumors of the cerebrum. The fine structure of 3 primitive neuroectodermal neoplasms of the cerebral hemispheres was studied. The predominant tumor cells were undifferentiated cells with prominent nuclei and scanty cytoplasm containing few organelles. Ultrastructural evidence suggesting differentiation into ependymal, neuronal and possibly astrocytic elements was also present. This study suggests that the cell of origin of this tumor is a primitive multipotential cell of the cerebrum."}
{"id": "PMID:222430", "title": "Ultrastructure of chondroid syringoma: role of the myoepithelial cell in the development of the mixed tumor of the skin and soft tissues.", "content": "The ultrastructure of a chondroid syringoma is described. The tumor nests are formed by clumps, solid cords and tubular structures distributed diffusely throughout a stroma of varying density. Two different types of cells form this tumor: dark cells forming the inner layer of the tubuloalveolar and ductal structures and having epithelial features, and light cells which form the outer layer of the tubular structures and show myoepithelial differentiation. The myoepithelial cells seem to be responsible for the production of the chondroid areas and thus the mixed appearance of the tumor. The epithelial cells forming the solid nests of the tumor show intracytoplasmic luminal formation and other features that favor the origin of chondroid syringoma from the eccrine sweat gland duct.", "contents": "Ultrastructure of chondroid syringoma: role of the myoepithelial cell in the development of the mixed tumor of the skin and soft tissues. The ultrastructure of a chondroid syringoma is described. The tumor nests are formed by clumps, solid cords and tubular structures distributed diffusely throughout a stroma of varying density. Two different types of cells form this tumor: dark cells forming the inner layer of the tubuloalveolar and ductal structures and having epithelial features, and light cells which form the outer layer of the tubular structures and show myoepithelial differentiation. The myoepithelial cells seem to be responsible for the production of the chondroid areas and thus the mixed appearance of the tumor. The epithelial cells forming the solid nests of the tumor show intracytoplasmic luminal formation and other features that favor the origin of chondroid syringoma from the eccrine sweat gland duct."}
{"id": "PMID:222431", "title": "Multiple myeloma in a mink handler following exposure to Aleutian disease.", "content": "Aleutian disease of mink is a viral illness characterized by systemic plasmocytosis and hypergammaglobulinemia. Some affected mink develop a monoclonal gammaglobulin spike and Bence-Jones proteinuria. A case of multiple myeloma in a mink handler with a 15-year history of exposure to Aleutian mink is presented. Previously reported cases of possible Aleutian disease (AD) in man are discussed and the pathogenesis of AD reviewed. Aleutian disease virus (ADV) may produce asymptomatic infection in exposed individuals. Available data suggest symptomatic disease in humans is extremely rare.", "contents": "Multiple myeloma in a mink handler following exposure to Aleutian disease. Aleutian disease of mink is a viral illness characterized by systemic plasmocytosis and hypergammaglobulinemia. Some affected mink develop a monoclonal gammaglobulin spike and Bence-Jones proteinuria. A case of multiple myeloma in a mink handler with a 15-year history of exposure to Aleutian mink is presented. Previously reported cases of possible Aleutian disease (AD) in man are discussed and the pathogenesis of AD reviewed. Aleutian disease virus (ADV) may produce asymptomatic infection in exposed individuals. Available data suggest symptomatic disease in humans is extremely rare."}
{"id": "PMID:222432", "title": "Rhabdomyosarcoma of the kidney in children.", "content": "Among 227 consecutive renal tumors examined from the Hospital de Ni\u00f1os de Buenos Aires, seven examples of a distinctive clinicopathological entity occurred. These renal neoplasms were all unilateral, grossly infiltrative without a definitive capsule. Microscopically, the lesion was characterized by a sarcomatous pattern with a rhabdomyoblastic differentiation. Four of them had regional lymph node involvement at surgery. Four developed bone metastases and none had lung metastases. In three instances, the bone metastases were histologically similar to the original neoplasm. The age of the patients ranged from 11 months to 5 1/2 years. A male predominance was observed. Two patients died; one is alive 5 years after surgery; three are alive with metastases; one has been followed for less than a year. In this study, it is proposed that another group of tumors be removed from the Wilms' tumor classification. The neoplasm has been described previously in the literature under several names. It is not clearly related clinicopathologically to nephroblastoma. The term rhabdomyosarcoma is proposed in view of its entirely different biological behavior.", "contents": "Rhabdomyosarcoma of the kidney in children. Among 227 consecutive renal tumors examined from the Hospital de Ni\u00f1os de Buenos Aires, seven examples of a distinctive clinicopathological entity occurred. These renal neoplasms were all unilateral, grossly infiltrative without a definitive capsule. Microscopically, the lesion was characterized by a sarcomatous pattern with a rhabdomyoblastic differentiation. Four of them had regional lymph node involvement at surgery. Four developed bone metastases and none had lung metastases. In three instances, the bone metastases were histologically similar to the original neoplasm. The age of the patients ranged from 11 months to 5 1/2 years. A male predominance was observed. Two patients died; one is alive 5 years after surgery; three are alive with metastases; one has been followed for less than a year. In this study, it is proposed that another group of tumors be removed from the Wilms' tumor classification. The neoplasm has been described previously in the literature under several names. It is not clearly related clinicopathologically to nephroblastoma. The term rhabdomyosarcoma is proposed in view of its entirely different biological behavior."}
{"id": "PMID:222433", "title": "Combination chemotherapy with vincristine and methotrexate for advanced refractory breast cancer.", "content": "Eighteen patients with advanced breast cancer refractory to combination chemotherapy with 5-FU, Adriamycin, Cytoxan (FAC) were treated with methotrexate 30 to 40 mg/m2 iv and vincristing 1.5 mg/m2 iv at weekly intervals. Of 17 evaluable patients, 4 (23%) achieved a partial remission with a median duration of remission of 6 months and a median survival of 10 months. In another seven of seventeen patients (41%) the disease remained stable. Toxicity was minimal.", "contents": "Combination chemotherapy with vincristine and methotrexate for advanced refractory breast cancer. Eighteen patients with advanced breast cancer refractory to combination chemotherapy with 5-FU, Adriamycin, Cytoxan (FAC) were treated with methotrexate 30 to 40 mg/m2 iv and vincristing 1.5 mg/m2 iv at weekly intervals. Of 17 evaluable patients, 4 (23%) achieved a partial remission with a median duration of remission of 6 months and a median survival of 10 months. In another seven of seventeen patients (41%) the disease remained stable. Toxicity was minimal."}
{"id": "PMID:222434", "title": "The role of chemotherapy in the treatment of Wilms' tumor.", "content": "The records of one hundred seventy-six patients with Wilm's tumor treated with transabdominal nephrectomy only or transabdominal nephrectomy, post-operative radiation therapy and several chemotherapy programs were reviewed. Three conclusions were reached: 1) The addition of postoperative radiation therapy and adjuvant chemotherapy has not improved the excellent, disease-free survival of patients with Stage I disease who were less than twenty-four months of age at diagnosis; 2) The addition of postoperative radiation therapy and adjuvant single agent chemotherapy has not improved the disease-free survival of patients with Stage II disease who were over twelve months of age at diagnosis; and 3) The use of combination chemotherapy with vincristine and actinomycin D has improved the disease-free survival of patients who present with Stage II disease.", "contents": "The role of chemotherapy in the treatment of Wilms' tumor. The records of one hundred seventy-six patients with Wilm's tumor treated with transabdominal nephrectomy only or transabdominal nephrectomy, post-operative radiation therapy and several chemotherapy programs were reviewed. Three conclusions were reached: 1) The addition of postoperative radiation therapy and adjuvant chemotherapy has not improved the excellent, disease-free survival of patients with Stage I disease who were less than twenty-four months of age at diagnosis; 2) The addition of postoperative radiation therapy and adjuvant single agent chemotherapy has not improved the disease-free survival of patients with Stage II disease who were over twelve months of age at diagnosis; and 3) The use of combination chemotherapy with vincristine and actinomycin D has improved the disease-free survival of patients who present with Stage II disease."}
{"id": "PMID:222435", "title": "Influence of cell type on failure pattern after irradiation for locally advanced carcinoma of the lung.", "content": "Patterns of failure after treatment for carcinoma of the lung were analyzed by the major WHO cell types. Only diagnoses of the review panel of the Veterans Administration Lung Group were used. First sites of progression were analyzed for 185 patients in a clinical trial, and cause of death was evaluated in 300 consecutive autopsies from VALG studies. Clinical progression was similar for all cell types--20% failed locally and 30% developed metastases. Carcinomatosis or brain metastasis caused death in only 27% of patients with squamous, in over half with large cell and adenocarcinoma, and in 70% of patients with small cell carcinoma. Complications of the local tumor (infection, hemorrhage, and respiratory failure) caused death in 50% of patients with squamous, in 1/3 with large cell and adenocacrinoma, and in 21% of those with small cell carcinoma. These clinical and autopsy data suggest the need for aggressive treatment of the local tumor in all cell types, and systemic therapy for small cell carcinoma. Both local and systemic approaches are needed for large cell and adenocarcinoma.", "contents": "Influence of cell type on failure pattern after irradiation for locally advanced carcinoma of the lung. Patterns of failure after treatment for carcinoma of the lung were analyzed by the major WHO cell types. Only diagnoses of the review panel of the Veterans Administration Lung Group were used. First sites of progression were analyzed for 185 patients in a clinical trial, and cause of death was evaluated in 300 consecutive autopsies from VALG studies. Clinical progression was similar for all cell types--20% failed locally and 30% developed metastases. Carcinomatosis or brain metastasis caused death in only 27% of patients with squamous, in over half with large cell and adenocarcinoma, and in 70% of patients with small cell carcinoma. Complications of the local tumor (infection, hemorrhage, and respiratory failure) caused death in 50% of patients with squamous, in 1/3 with large cell and adenocacrinoma, and in 21% of those with small cell carcinoma. These clinical and autopsy data suggest the need for aggressive treatment of the local tumor in all cell types, and systemic therapy for small cell carcinoma. Both local and systemic approaches are needed for large cell and adenocarcinoma."}
{"id": "PMID:222436", "title": "The EBV-carrying, beta2M/HLA deficient Burkitt lymphoma line Daudi is sensitive to EBV-specific killer T-cells of mononucleosis patients.", "content": "The beta2-microglobulin/HLA deficient Burkitt lymphoma line Daudi was tested for sensitivity to EBV-specific cytotoxicity mediated by natural killer (NK)-depleted T-cells from acute mononucleosis patients. While the Daudi line was not as sensitive as the reference EBV-genome-positive target line, it was clearly sensitive in the majority of cases. This would speak against a major role of syngeneic restriction in this system.", "contents": "The EBV-carrying, beta2M/HLA deficient Burkitt lymphoma line Daudi is sensitive to EBV-specific killer T-cells of mononucleosis patients. The beta2-microglobulin/HLA deficient Burkitt lymphoma line Daudi was tested for sensitivity to EBV-specific cytotoxicity mediated by natural killer (NK)-depleted T-cells from acute mononucleosis patients. While the Daudi line was not as sensitive as the reference EBV-genome-positive target line, it was clearly sensitive in the majority of cases. This would speak against a major role of syngeneic restriction in this system."}
{"id": "PMID:222437", "title": "Circulating immune complexes in sera of hamsters bearing simian virus 40-induced tumours.", "content": "Reported previously in certain human carcinomas and rat and mouse experimental tumor systems, circulating immune complexes (IC) have now been detected in Syrian hamsters bearing tumors produced by injection with syngeneic TSV5Cl2 cells. IC were detected by the Raji cell radioimmune assay, adapted for use in hamster sera. A novel feature of this test is the use of a stable covalently linked hamster immunoglobulin G aggregate as the reaction standard. Stable over six months on storage at -70 degrees and showing no tendency to form precipitates on thawing or during test procedures, this preparation greatly facilitated quantitation of hamster IC by Raji cells. Seven of 19 sera of hamsters bearing SV40-induced tumors from 60 to 128 days had IC concentrations exceeding 40 microgram aggregated hamster immunoglobulin G equivalents per ml, as contrasted to IC levels of less than 25 microgram for 19 age-matched normal hamsters. There appeared to be no significant correlation between IC levels and tumor weight or duration of tumor within the hamster host. The results suggest a complex relationship between IC and a number of factors connected with tumor growth.", "contents": "Circulating immune complexes in sera of hamsters bearing simian virus 40-induced tumours. Reported previously in certain human carcinomas and rat and mouse experimental tumor systems, circulating immune complexes (IC) have now been detected in Syrian hamsters bearing tumors produced by injection with syngeneic TSV5Cl2 cells. IC were detected by the Raji cell radioimmune assay, adapted for use in hamster sera. A novel feature of this test is the use of a stable covalently linked hamster immunoglobulin G aggregate as the reaction standard. Stable over six months on storage at -70 degrees and showing no tendency to form precipitates on thawing or during test procedures, this preparation greatly facilitated quantitation of hamster IC by Raji cells. Seven of 19 sera of hamsters bearing SV40-induced tumors from 60 to 128 days had IC concentrations exceeding 40 microgram aggregated hamster immunoglobulin G equivalents per ml, as contrasted to IC levels of less than 25 microgram for 19 age-matched normal hamsters. There appeared to be no significant correlation between IC levels and tumor weight or duration of tumor within the hamster host. The results suggest a complex relationship between IC and a number of factors connected with tumor growth."}
{"id": "PMID:222438", "title": "Characterization of a tumor cell surface protein with heterologous antisera to a spontaneous BALB/c lung carcinoma.", "content": "Line 1, a spontaneous alveolar carcinoma from a BALB/c mouse, is highly metastatic and weakly antigenic in the syngeneic host. Sera and enriched antibody preparations were made specific for line 1 cells by in vitro and in vivo absorptions. By lactoperoxidase-catalyzed radioiodination of cell surface protein followed by precipitation with specific antibodies, a protein with a molecular weight of about 180,000 (designated TSP-180) was identified that was present on line 1 cells but not on normal lung cells or Moloney sarcoma tumor cells. Studies of competition for immune precipitation of TSP-180 by unlabeled protein preparations from various sources indicate that (a) TSP-180 is present in tumor cells of various culture passage levels, (b) tumor cells grown i.m. also contain TSP-180, and (c) normal lung proteins compete weakly, and only at very high protein concentrations. A protein similar to TSP-180 was detected on Madison 109 carcinoma and on three other lung carcinomas adapted to culture. Experiments with specific antisera show that TSP-180 is not lactoperoxidase, fetal bovine serum protein, large external transformation-sensitive protein, or an antigen related to murine leukemia virus proteins.", "contents": "Characterization of a tumor cell surface protein with heterologous antisera to a spontaneous BALB/c lung carcinoma. Line 1, a spontaneous alveolar carcinoma from a BALB/c mouse, is highly metastatic and weakly antigenic in the syngeneic host. Sera and enriched antibody preparations were made specific for line 1 cells by in vitro and in vivo absorptions. By lactoperoxidase-catalyzed radioiodination of cell surface protein followed by precipitation with specific antibodies, a protein with a molecular weight of about 180,000 (designated TSP-180) was identified that was present on line 1 cells but not on normal lung cells or Moloney sarcoma tumor cells. Studies of competition for immune precipitation of TSP-180 by unlabeled protein preparations from various sources indicate that (a) TSP-180 is present in tumor cells of various culture passage levels, (b) tumor cells grown i.m. also contain TSP-180, and (c) normal lung proteins compete weakly, and only at very high protein concentrations. A protein similar to TSP-180 was detected on Madison 109 carcinoma and on three other lung carcinomas adapted to culture. Experiments with specific antisera show that TSP-180 is not lactoperoxidase, fetal bovine serum protein, large external transformation-sensitive protein, or an antigen related to murine leukemia virus proteins."}
{"id": "PMID:222440", "title": "Effects of protease inhibitors on chemical induction of type C virus.", "content": "A role for proteolysis during chemical induction of endogenous xenotropic Type C virus from Kirsten sarcoma virus-transformed mouse cells was examined. Two distinct classes of protease inhibitors, the trypsin inhibitor, alpha-N-tosyl-L-lysine chloromethyl ketone, and two naturally occurring oligopeptide inhibitors, antipain and leupeptin, were found to inhibit induction of virus by cycloheximide and histidinol. Virus activation by 5-iododeoxyuridine was inhibited to a lesser degree. During the time cells were exposed to these compounds, there was little inhibition of [3H]uridine incorporation into total cellular RNA or polyadenylic acid cytoplasmic messenger RNA, suggesting that inhibition of proteolysis, and not RNA transcription, was responsible for blocking virus induction.", "contents": "Effects of protease inhibitors on chemical induction of type C virus. A role for proteolysis during chemical induction of endogenous xenotropic Type C virus from Kirsten sarcoma virus-transformed mouse cells was examined. Two distinct classes of protease inhibitors, the trypsin inhibitor, alpha-N-tosyl-L-lysine chloromethyl ketone, and two naturally occurring oligopeptide inhibitors, antipain and leupeptin, were found to inhibit induction of virus by cycloheximide and histidinol. Virus activation by 5-iododeoxyuridine was inhibited to a lesser degree. During the time cells were exposed to these compounds, there was little inhibition of [3H]uridine incorporation into total cellular RNA or polyadenylic acid cytoplasmic messenger RNA, suggesting that inhibition of proteolysis, and not RNA transcription, was responsible for blocking virus induction."}
{"id": "PMID:222442", "title": "Study of the cytotoxicity and metabolism of 4-amino-3-carboxamido-1-(beta-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidine using inhibitors of adenosine kinase and adenosine deaminase.", "content": "The greater in vivo antitumor activity of 4-amino-3-carboxamido-1-(beta-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidine (APPCR) in comparison to the parent compound 4-amino-1-(beta-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidine (APPR) may involve intrinsic differences in the effects of these two compounds on cells, as well as in their metabolisms. In studies with L1210 cells in vitro, growth inhibition by APPCR for 36 hr or more was found to be cytocidal, while growth inhibition by APPR was cytostatic in that a substantial fraction of the cells survived 36 or 72 hr of exposure to growth-inhibiting concentrations of APPR. It appears that this difference in the cellular effects of APPCR and APPR is not related to differences in the requirement for activation by phosphorylation or in susceptibility to inactivation by deamination. However, deamination may limit the effectiveness of APPR in vivo since it is a substrate for adenosine deaminase, while deamination of APPCR is not detectable.", "contents": "Study of the cytotoxicity and metabolism of 4-amino-3-carboxamido-1-(beta-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidine using inhibitors of adenosine kinase and adenosine deaminase. The greater in vivo antitumor activity of 4-amino-3-carboxamido-1-(beta-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidine (APPCR) in comparison to the parent compound 4-amino-1-(beta-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidine (APPR) may involve intrinsic differences in the effects of these two compounds on cells, as well as in their metabolisms. In studies with L1210 cells in vitro, growth inhibition by APPCR for 36 hr or more was found to be cytocidal, while growth inhibition by APPR was cytostatic in that a substantial fraction of the cells survived 36 or 72 hr of exposure to growth-inhibiting concentrations of APPR. It appears that this difference in the cellular effects of APPCR and APPR is not related to differences in the requirement for activation by phosphorylation or in susceptibility to inactivation by deamination. However, deamination may limit the effectiveness of APPR in vivo since it is a substrate for adenosine deaminase, while deamination of APPCR is not detectable."}
{"id": "PMID:222443", "title": "Prolonged induction of hepatic ornithine decarboxylase and its relation to cyclic adenosine 3':5'-monophosphate-dependent protein kinase activation after a single administration of diethylnitrosamine.", "content": "After a single injection of diethylnitrosamine (200 mg/kg), there was a rapid increase in the activity ratio of hepatic cyclic adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase (within 1 hr) followed by the induction of ornithine decarboxylase which was detectable by 3 hr. Both the cyclic AMP-dependent protein kinase activity ratio and the activity of ornithine decarboxylase were significantly elevated above controls for 7 days following the administration of diethylnitrosamine. A single noncarcinogenic dose of diethylnitrosamine (25 mg/kg) did not increase the cyclic AMP-dependent protein kinase activity ratio or induce ornithine decarboxylase activity at 24 hr postadministration. However, serial administration of diethylnitrosamine (25 mg/kg) for 4 or 7 days resulted in an increased activity ratio of cyclic AMP-dependent protein kinase and increased ornithine decarboxylase activity. This is the first report of a prolonged increase in both the activity ratio of hepatic cyclic AMP-dependent protein kinase and the activity of ornithine decarboxylase in response to a single carcinogenic dose of diethylnitrosamine.", "contents": "Prolonged induction of hepatic ornithine decarboxylase and its relation to cyclic adenosine 3':5'-monophosphate-dependent protein kinase activation after a single administration of diethylnitrosamine. After a single injection of diethylnitrosamine (200 mg/kg), there was a rapid increase in the activity ratio of hepatic cyclic adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase (within 1 hr) followed by the induction of ornithine decarboxylase which was detectable by 3 hr. Both the cyclic AMP-dependent protein kinase activity ratio and the activity of ornithine decarboxylase were significantly elevated above controls for 7 days following the administration of diethylnitrosamine. A single noncarcinogenic dose of diethylnitrosamine (25 mg/kg) did not increase the cyclic AMP-dependent protein kinase activity ratio or induce ornithine decarboxylase activity at 24 hr postadministration. However, serial administration of diethylnitrosamine (25 mg/kg) for 4 or 7 days resulted in an increased activity ratio of cyclic AMP-dependent protein kinase and increased ornithine decarboxylase activity. This is the first report of a prolonged increase in both the activity ratio of hepatic cyclic AMP-dependent protein kinase and the activity of ornithine decarboxylase in response to a single carcinogenic dose of diethylnitrosamine."}
{"id": "PMID:222445", "title": "Relationship between the intracellular cyclic adenosine 3':5'-monophosphate level of tumor cells and their sensitivity to killing by antibody and complement.", "content": "Metabolic inhibitors which have been shown to increase the sensitivity of the guinea pig hepatoma, line 10, to antibody-guinea pig complement killing were tested for their effect on the intracellular cyclic adenosine 3':5'-monophosphate (cAMP) level of the line 10 cells. It was found that cells rendered sensitive to antibody-guinea pig complement killing following drug treatment showed a decrease in their intracellular cAMP levels. Increased susceptibility to lysis was always associated with decreased intracellular cAMP levels. Optimal doses of certain inhibitors effectively increased the sensitivity of the cells to complement-dependent lysis and decreased the intracellular cAMP levels. Other drugs which did not increase sensitivity of the cells to lysis also failed to decrease the intracellular cAMP levels. No experimental conditions were found in which intracellular cAMP levels were decreased without an increase in the susceptibility of the cells to antibody-guinea pig complement killing.", "contents": "Relationship between the intracellular cyclic adenosine 3':5'-monophosphate level of tumor cells and their sensitivity to killing by antibody and complement. Metabolic inhibitors which have been shown to increase the sensitivity of the guinea pig hepatoma, line 10, to antibody-guinea pig complement killing were tested for their effect on the intracellular cyclic adenosine 3':5'-monophosphate (cAMP) level of the line 10 cells. It was found that cells rendered sensitive to antibody-guinea pig complement killing following drug treatment showed a decrease in their intracellular cAMP levels. Increased susceptibility to lysis was always associated with decreased intracellular cAMP levels. Optimal doses of certain inhibitors effectively increased the sensitivity of the cells to complement-dependent lysis and decreased the intracellular cAMP levels. Other drugs which did not increase sensitivity of the cells to lysis also failed to decrease the intracellular cAMP levels. No experimental conditions were found in which intracellular cAMP levels were decreased without an increase in the susceptibility of the cells to antibody-guinea pig complement killing."}
{"id": "PMID:222446", "title": "Analysis of chromosomes, nucleic acids, and polypeptides in hamster cells transformed by herpes simplex virus type 2.", "content": "Syrian hamster embryo fibroblasts were oncogenically transformed by UV-inactivated Herpes simplex type 2. Eighteen clones were isolated shortly after transformation occurred. Two clones and their tumor derivatives were studied using several techniques. The karyotype analysis revealed different chromosome patterns in the two clones and a tendency toward hypodiploidy in the tumor derivatives. All of these cell lines were shown by molecular hybridization to contain 40% of the HSV-genome in several copies. The viral DNA sequence complexity was retained in the tumor derivatives, but a decrease in the copy number was observed. Viral RNA's were detected by in situ hybridization in all the lines that were tested. Viral antigens could be observed in these transformed cells by immunofluorescence. Finally, polypeptide analysis showed three differences between normal and transformed cells.", "contents": "Analysis of chromosomes, nucleic acids, and polypeptides in hamster cells transformed by herpes simplex virus type 2. Syrian hamster embryo fibroblasts were oncogenically transformed by UV-inactivated Herpes simplex type 2. Eighteen clones were isolated shortly after transformation occurred. Two clones and their tumor derivatives were studied using several techniques. The karyotype analysis revealed different chromosome patterns in the two clones and a tendency toward hypodiploidy in the tumor derivatives. All of these cell lines were shown by molecular hybridization to contain 40% of the HSV-genome in several copies. The viral DNA sequence complexity was retained in the tumor derivatives, but a decrease in the copy number was observed. Viral RNA's were detected by in situ hybridization in all the lines that were tested. Viral antigens could be observed in these transformed cells by immunofluorescence. Finally, polypeptide analysis showed three differences between normal and transformed cells."}
{"id": "PMID:222447", "title": "Amplification of growth inhibition by glucocorticoid on L5178Y and L1210 lymphoblasts in vivo.", "content": "One component of a factor in Proteus mirabilis (Factor 1) which specifically amplifies the induction of several liver enzymes by glucocorticoid in target cells also increases the growth inhibition of glucocorticoid on the ascitic form of L1210 cells and solid tumors of L5178Y lymphoblasts in vivo. The growth of L5U78Y and L1210 lymphoblasts was inhibited by a triamcinolone acetonide dose of over 0.5 to 1.0 mg/kg body weight. Factor 1 increased the inhibitory effect of a triamcinolone acetonide dose of less than 4.0 mg/kg bodyweight but had little effect on the effects of doses of over 4.0 mg. Factor 1 (10 biological units/kg body weight) itself also caused marked inhibition of the growth of these lymphoblasts without affecting the body weight or adrenal gland weight, its effect being equivalent to that of 3- to 4-mg/kg body weight doses of triamcinolone acetonide alone. There was no significant difference in the level of plasma total corticoids or that of plasma adrenocorticotropic hormone between rats treated with 0.9% NaCl solution or those treated with Factor 1, and Factor 1 had no cytotoxic effec on cultured L5178Y lymphoblasts. Thus, Factor 1 may amplify the effect of physiological level of glucocorticoid in mice sufficiently to inhibit the growth of these lymphoblasts without causing any significant side effects to the host animal.", "contents": "Amplification of growth inhibition by glucocorticoid on L5178Y and L1210 lymphoblasts in vivo. One component of a factor in Proteus mirabilis (Factor 1) which specifically amplifies the induction of several liver enzymes by glucocorticoid in target cells also increases the growth inhibition of glucocorticoid on the ascitic form of L1210 cells and solid tumors of L5178Y lymphoblasts in vivo. The growth of L5U78Y and L1210 lymphoblasts was inhibited by a triamcinolone acetonide dose of over 0.5 to 1.0 mg/kg body weight. Factor 1 increased the inhibitory effect of a triamcinolone acetonide dose of less than 4.0 mg/kg bodyweight but had little effect on the effects of doses of over 4.0 mg. Factor 1 (10 biological units/kg body weight) itself also caused marked inhibition of the growth of these lymphoblasts without affecting the body weight or adrenal gland weight, its effect being equivalent to that of 3- to 4-mg/kg body weight doses of triamcinolone acetonide alone. There was no significant difference in the level of plasma total corticoids or that of plasma adrenocorticotropic hormone between rats treated with 0.9% NaCl solution or those treated with Factor 1, and Factor 1 had no cytotoxic effec on cultured L5178Y lymphoblasts. Thus, Factor 1 may amplify the effect of physiological level of glucocorticoid in mice sufficiently to inhibit the growth of these lymphoblasts without causing any significant side effects to the host animal."}
{"id": "PMID:222448", "title": "Nonspecific adjuvant immunotherapy of lung cancer with cell wall skeleton of Mycobacterium bovis Bacillus Calmette-Gu\u00e9rin.", "content": "Nonspecific adjuvant immunotherapy with Bacillus Calmette-Gu\u00e9rin cell wall skeleton (BCG-CWS) was given to 155 lung cancer patients. Clinical effects of the BCG-CWS treatment were estimated by comparing the survival of the BCG-CWS group with that of a historical control group on the basis of 4-year results. Significant prolongation of survival time has been observed in Clinical Stages II, III (M0) and III (M1). However, most Stage III patients who were given the BCG-CWS treatment died of cancer itself after marked prolongation of survival time. An increase in complete cure rate has been expected only in Stages I and II. Surgicopathological staging was used in resected cases. Resected cases at any stage were sensitive to treatment with BCG-CWS. Histologically, all types of lung cancer including squamous cell carcinoma, adenocarcinoma, and anaplastic carcinoma were sensitive to treatment with BCG-CWS. Intrapleural administration of BCG-CWS to patients with malignant pleurisy was effective in controlling the pleural effusion and prolonging the survival time. No serious complication has been experienced in our study.", "contents": "Nonspecific adjuvant immunotherapy of lung cancer with cell wall skeleton of Mycobacterium bovis Bacillus Calmette-Gu\u00e9rin. Nonspecific adjuvant immunotherapy with Bacillus Calmette-Gu\u00e9rin cell wall skeleton (BCG-CWS) was given to 155 lung cancer patients. Clinical effects of the BCG-CWS treatment were estimated by comparing the survival of the BCG-CWS group with that of a historical control group on the basis of 4-year results. Significant prolongation of survival time has been observed in Clinical Stages II, III (M0) and III (M1). However, most Stage III patients who were given the BCG-CWS treatment died of cancer itself after marked prolongation of survival time. An increase in complete cure rate has been expected only in Stages I and II. Surgicopathological staging was used in resected cases. Resected cases at any stage were sensitive to treatment with BCG-CWS. Histologically, all types of lung cancer including squamous cell carcinoma, adenocarcinoma, and anaplastic carcinoma were sensitive to treatment with BCG-CWS. Intrapleural administration of BCG-CWS to patients with malignant pleurisy was effective in controlling the pleural effusion and prolonging the survival time. No serious complication has been experienced in our study."}
{"id": "PMID:222449", "title": "Combination chemotherapy for islet cell carcinoma and metastatic carcinoid tumors with 5-fluorouracil and streptozotocin.", "content": "The results of combination chemotherapy with intermittent courses of 5-fluorouracil and streptozotocin in ten patients with metastatic carcinoid tumors and in eight patients with islet cell carcinoma are reported. Objective responses occurred in two of ten and in two of seven evaluable patients respectively. Biochemical responses occurred in an additional two patients with carcinoid. No improvement over single-agent chemotherapy and no effects on survival were noted.", "contents": "Combination chemotherapy for islet cell carcinoma and metastatic carcinoid tumors with 5-fluorouracil and streptozotocin. The results of combination chemotherapy with intermittent courses of 5-fluorouracil and streptozotocin in ten patients with metastatic carcinoid tumors and in eight patients with islet cell carcinoma are reported. Objective responses occurred in two of ten and in two of seven evaluable patients respectively. Biochemical responses occurred in an additional two patients with carcinoid. No improvement over single-agent chemotherapy and no effects on survival were noted."}
{"id": "PMID:222451", "title": "Structural changes occurring in internal tissue of the duck (Anas platyrhynchos) following adenohypophysectomy and treatment in vivo and in vitro with corticotropin.", "content": "Adrenal glands from ACTH-treated intact ducks and chronically adenohypophysectomized ducks showed clear zonation into a subcapsular zone (SCZ) and an inner zone (IZ). Adenohypophysectomy caused ultrastructural changes in the IZ but not in the SCZ cells. These included increases in lipid droplets, changes in mitochondrial cristae from tubular to shelf-like, and changes in the shape of the nuclei from spherical to crenated. These changes were reversed by treatment with ACTH. Also, cells of the IZ, but not the SCZ, of adrenals from intact birds given ACTH showed more SER, more dense bodies, fewer lipid droplets and more prominent Golgi complexes. IZ cells incubated in buffer containing no ACTH developed mitochondria with shelf-like cristae and numerous opaque granules in the matrix. Exposure to buffer containing ACTH caused the mitochondrial cristae to become tubular and the matrix granules either decreased in number or disappeared. The granules could be extracted by incubating sections with chelating agents. The mitochondria in SCZ cells did not respond structurally to the presence of ACTH in the incubation medium but the matrix granules, like those in IZ cells, responded to the presence of chelating agents.", "contents": "Structural changes occurring in internal tissue of the duck (Anas platyrhynchos) following adenohypophysectomy and treatment in vivo and in vitro with corticotropin. Adrenal glands from ACTH-treated intact ducks and chronically adenohypophysectomized ducks showed clear zonation into a subcapsular zone (SCZ) and an inner zone (IZ). Adenohypophysectomy caused ultrastructural changes in the IZ but not in the SCZ cells. These included increases in lipid droplets, changes in mitochondrial cristae from tubular to shelf-like, and changes in the shape of the nuclei from spherical to crenated. These changes were reversed by treatment with ACTH. Also, cells of the IZ, but not the SCZ, of adrenals from intact birds given ACTH showed more SER, more dense bodies, fewer lipid droplets and more prominent Golgi complexes. IZ cells incubated in buffer containing no ACTH developed mitochondria with shelf-like cristae and numerous opaque granules in the matrix. Exposure to buffer containing ACTH caused the mitochondrial cristae to become tubular and the matrix granules either decreased in number or disappeared. The granules could be extracted by incubating sections with chelating agents. The mitochondria in SCZ cells did not respond structurally to the presence of ACTH in the incubation medium but the matrix granules, like those in IZ cells, responded to the presence of chelating agents."}
{"id": "PMID:222452", "title": "Localization of ACTH in the human hypothalamus.", "content": "Using an antiserum to porcine ACTH and the unlabeled antibody preoxidase-antiperoxidase technique, we have found that ACTH is present in neuronal cell bodies located exclusively in the arcuate nucleus of the human hypothalamus. ACTH-containing fibers are distributed extensively throughout the hypothalamus with a greatest density in the periventricular nucleus. No concentration of ACTH fibers could be observed in the neurovascular zone of the pituitary stalk.", "contents": "Localization of ACTH in the human hypothalamus. Using an antiserum to porcine ACTH and the unlabeled antibody preoxidase-antiperoxidase technique, we have found that ACTH is present in neuronal cell bodies located exclusively in the arcuate nucleus of the human hypothalamus. ACTH-containing fibers are distributed extensively throughout the hypothalamus with a greatest density in the periventricular nucleus. No concentration of ACTH fibers could be observed in the neurovascular zone of the pituitary stalk."}
{"id": "PMID:222453", "title": "Hybrid pigment organelles in an invertebrate.", "content": "Observations of a number of vertebrate chromatophores have revealed the presence of more than one type of pigment organelles, suggesting that the different types are all derived from an equipotential organelle able to differentiate into any of the major pigment-containing organelles (Bagnara, 1972). Observations are presented concerning the occurrence of hybrid pigment inclusions, i.e., all kinds of intergrades between melanosomes, pterinosomes, and reflecting platelets in pigment cells of the daddy-long-legs. It therefore seems possible that pigment organelles in some invertebrates may also be derived from a common pluripotential primordial organelle.", "contents": "Hybrid pigment organelles in an invertebrate. Observations of a number of vertebrate chromatophores have revealed the presence of more than one type of pigment organelles, suggesting that the different types are all derived from an equipotential organelle able to differentiate into any of the major pigment-containing organelles (Bagnara, 1972). Observations are presented concerning the occurrence of hybrid pigment inclusions, i.e., all kinds of intergrades between melanosomes, pterinosomes, and reflecting platelets in pigment cells of the daddy-long-legs. It therefore seems possible that pigment organelles in some invertebrates may also be derived from a common pluripotential primordial organelle."}
{"id": "PMID:222454", "title": "The cytoskeletal framework and poliovirus metabolism.", "content": "The cytoskeletal framework prepared by detergent lysis of suspension-grown HeLa cells is compared to the structure obtained from poliovirus-infected cells. This framework, which retains major features of cell morphology and carries the cellular polyribosomes as well as the major structural filaments, is profoundly reorganized following virus infection. This reorganization underlies, at least in part, the morphological changes termed the \"cytoplasmic effect.\" These cytoskeletal changes appear related to the involvement of the framework with viral-specific metabolism. Extensive cytoskeleton alterations occur even when guanidine inhibits viral replication, and thus result from small amounts of early viral products. The normally spheroidal nucleus deforms, allowing a modified region of the cytoplasm to occupy a central position in the cell, and many membrane-enclosed vesicles peculiar to the infected cell are elaborated here. The skeleton preparation reveals that this region contains intermediate filaments arranged in a pattern unique to infected cells. Further changes occur when viral replication is permitted. The central region filaments become coated with darkly staining material which may be viral RNA. Numerous small particles appear on the filaments which resemble partially assembled virions. Mature virions, however, have no affinity for the cytoskeleton and appear to be free in the cytoplasm. Host cell messenger RNA, normally attached to the skeletal framework, is released in infected cells and is replaced by the viral-specific polyribosomes. The trabecular network which carries polyribosomes appears to be rearranged; the viral polyribosomes are located principally at the cell periphery and are excluded from the central region. The viral replication complex with its double-stranded RNA is also attached to the skeletal framework and may comprise the dark staining material coating the filaments of the central cell region.", "contents": "The cytoskeletal framework and poliovirus metabolism. The cytoskeletal framework prepared by detergent lysis of suspension-grown HeLa cells is compared to the structure obtained from poliovirus-infected cells. This framework, which retains major features of cell morphology and carries the cellular polyribosomes as well as the major structural filaments, is profoundly reorganized following virus infection. This reorganization underlies, at least in part, the morphological changes termed the \"cytoplasmic effect.\" These cytoskeletal changes appear related to the involvement of the framework with viral-specific metabolism. Extensive cytoskeleton alterations occur even when guanidine inhibits viral replication, and thus result from small amounts of early viral products. The normally spheroidal nucleus deforms, allowing a modified region of the cytoplasm to occupy a central position in the cell, and many membrane-enclosed vesicles peculiar to the infected cell are elaborated here. The skeleton preparation reveals that this region contains intermediate filaments arranged in a pattern unique to infected cells. Further changes occur when viral replication is permitted. The central region filaments become coated with darkly staining material which may be viral RNA. Numerous small particles appear on the filaments which resemble partially assembled virions. Mature virions, however, have no affinity for the cytoskeleton and appear to be free in the cytoplasm. Host cell messenger RNA, normally attached to the skeletal framework, is released in infected cells and is replaced by the viral-specific polyribosomes. The trabecular network which carries polyribosomes appears to be rearranged; the viral polyribosomes are located principally at the cell periphery and are excluded from the central region. The viral replication complex with its double-stranded RNA is also attached to the skeletal framework and may comprise the dark staining material coating the filaments of the central cell region."}
{"id": "PMID:222456", "title": "Integration of the DNA of mouse mammary tumor virus in virus-infected normal and neoplastic tissue of the mouse.", "content": "We have used restriction endonucleases which cleave the DNA of mouse mammary tumor virus (MMTV) at one site (Eco RI) and several sites (Pst I, Sac I and Bam HI) to study infection and mammary tumorigenesis in mice. Proviruses acquired during infection of BALB/c mice foster-nursed by virus-producing C3H females can be distinguished from the MMTV proviruses endogenous to uninfected BALB/c mice by the nature of the fragments generated with Pst I and Bam HI. Using this assay, we show that lactating mammary glands as well as mammary tumors from BALB/cfC3H mice have acquired MMTV DNA, and that a minimum of approximately 10% of normal glandular cells can be infected. The new proviruses appear to be linked to cellular DNA of mammary tumors and infected lactating mammary glands within a limited region (0.2 x 10(6) daltons) of the viral DNA; the location of this region, based upon mapping studies with unintegrated MMTV DNA, suggests that the orientation of these proviruses is colinear with linear DNA synthesized in infected cells and thus approximately colinear with the viral RNA. Comparisons of many mammary tumors and studies of lactating mammary glands with a high proportion of independently infected cells indicate that a large number of sites in the cellular genome can accommodate a new provirus; the acquired proviruses are rarely, if ever, found in tandem with each other or with endogenous proviruses. We cannot, however, distinguish between random integration and integration into a large number of preferred sites in the host genome. Since Eco RI and Bam HI cleavage of DNA from each mammary tumor generates a unique set of viral-specific fragments, we propose that the tumors are composed principally of cells derived from a subset of the many infected cells in a mammary gland; this proposal is supported by our finding that Eco RI digestion of DNA from several transplants of a primary tumor yields the pattern characteristic of the primary tumor.", "contents": "Integration of the DNA of mouse mammary tumor virus in virus-infected normal and neoplastic tissue of the mouse. We have used restriction endonucleases which cleave the DNA of mouse mammary tumor virus (MMTV) at one site (Eco RI) and several sites (Pst I, Sac I and Bam HI) to study infection and mammary tumorigenesis in mice. Proviruses acquired during infection of BALB/c mice foster-nursed by virus-producing C3H females can be distinguished from the MMTV proviruses endogenous to uninfected BALB/c mice by the nature of the fragments generated with Pst I and Bam HI. Using this assay, we show that lactating mammary glands as well as mammary tumors from BALB/cfC3H mice have acquired MMTV DNA, and that a minimum of approximately 10% of normal glandular cells can be infected. The new proviruses appear to be linked to cellular DNA of mammary tumors and infected lactating mammary glands within a limited region (0.2 x 10(6) daltons) of the viral DNA; the location of this region, based upon mapping studies with unintegrated MMTV DNA, suggests that the orientation of these proviruses is colinear with linear DNA synthesized in infected cells and thus approximately colinear with the viral RNA. Comparisons of many mammary tumors and studies of lactating mammary glands with a high proportion of independently infected cells indicate that a large number of sites in the cellular genome can accommodate a new provirus; the acquired proviruses are rarely, if ever, found in tandem with each other or with endogenous proviruses. We cannot, however, distinguish between random integration and integration into a large number of preferred sites in the host genome. Since Eco RI and Bam HI cleavage of DNA from each mammary tumor generates a unique set of viral-specific fragments, we propose that the tumors are composed principally of cells derived from a subset of the many infected cells in a mammary gland; this proposal is supported by our finding that Eco RI digestion of DNA from several transplants of a primary tumor yields the pattern characteristic of the primary tumor."}
{"id": "PMID:222458", "title": "Multiple 5' terminal cap structures in late polyoma virus RNA.", "content": "Nuclear and cytoplasmic polyoma virus-specific RNA extracted from 32P-labeled mouse embryo cells late during productive viral infection was analyzed for the presence of 5' terminal capped structures by complete digestion with RNAases T1, T2 and A, followed by two-dimensional electrophoretic fractionation. Seven major cap I structures (m7 GpppNm1pN2p) were observed in both cases. These termini were further characterized by digestion with penicillium nuclease P1, followed by product analysis in a variety of alternative separate systems. Each structure had an individual combination of N1 and N2 nucleotides, where N1 was always a purine nucleotide but N2 was any nucleotide subject to the single exception that m7GpppGmpCp is found only in low yield. Four different cap II derivatives (m7GpppNm1pNm2pN3p) of four of the cap I structures were also detected in cytoplasmic RNA. None of the termini described derived from contaminating host cell RNA. All of these cap structures mapped on the polyoma viral DNA genome between 66 and 71 map units, a region distant from the 5' end of the bodies of two of the three late polyoma mRNAs. All the polyoma virus-specific cap structures, however, were present in each of the purified 16S, 18S and 19s late mRNAs. These data suggested that families of capped leader sequences of varying sizes are attached to the main body of each late polyoma mRNA species by a splicing mechanism.", "contents": "Multiple 5' terminal cap structures in late polyoma virus RNA. Nuclear and cytoplasmic polyoma virus-specific RNA extracted from 32P-labeled mouse embryo cells late during productive viral infection was analyzed for the presence of 5' terminal capped structures by complete digestion with RNAases T1, T2 and A, followed by two-dimensional electrophoretic fractionation. Seven major cap I structures (m7 GpppNm1pN2p) were observed in both cases. These termini were further characterized by digestion with penicillium nuclease P1, followed by product analysis in a variety of alternative separate systems. Each structure had an individual combination of N1 and N2 nucleotides, where N1 was always a purine nucleotide but N2 was any nucleotide subject to the single exception that m7GpppGmpCp is found only in low yield. Four different cap II derivatives (m7GpppNm1pNm2pN3p) of four of the cap I structures were also detected in cytoplasmic RNA. None of the termini described derived from contaminating host cell RNA. All of these cap structures mapped on the polyoma viral DNA genome between 66 and 71 map units, a region distant from the 5' end of the bodies of two of the three late polyoma mRNAs. All the polyoma virus-specific cap structures, however, were present in each of the purified 16S, 18S and 19s late mRNAs. These data suggested that families of capped leader sequences of varying sizes are attached to the main body of each late polyoma mRNA species by a splicing mechanism."}
{"id": "PMID:222459", "title": "Amplification in the leader sequence of late polyoma virus mRNAs.", "content": "Ribonuclease T1 fingerprints of the three \"late\" polyoma virus mRNAs show that oligonucleotides of the leader sequence are present in multiple copies in each mRNA. These oligonucleotides, however, appear unimolar in fingerprints of complete, continuous transcripts of the late strand of the viral DNA. Oligonucleotides which are represented only once in the DNA are thus reiterated in the mature mRNAs. Consequently, when mRNA was hybridized to the leader region of immobilized viral DNA, those copies present in excess of their genomic representation failed to hybridize and were released by RNAase treatment. Analysis of the RNAase-resistant hybrids revealed a series of leader species with complex sequence arrangements. We suggest that these complicated reiterated sequences are generated during the processing of a precursor RNA which extends several times around the genome. This RNA would be shortened by a series of splicing reactions which conserve sequences from the leader region and attach them to a suitable coding sequence.", "contents": "Amplification in the leader sequence of late polyoma virus mRNAs. Ribonuclease T1 fingerprints of the three \"late\" polyoma virus mRNAs show that oligonucleotides of the leader sequence are present in multiple copies in each mRNA. These oligonucleotides, however, appear unimolar in fingerprints of complete, continuous transcripts of the late strand of the viral DNA. Oligonucleotides which are represented only once in the DNA are thus reiterated in the mature mRNAs. Consequently, when mRNA was hybridized to the leader region of immobilized viral DNA, those copies present in excess of their genomic representation failed to hybridize and were released by RNAase treatment. Analysis of the RNAase-resistant hybrids revealed a series of leader species with complex sequence arrangements. We suggest that these complicated reiterated sequences are generated during the processing of a precursor RNA which extends several times around the genome. This RNA would be shortened by a series of splicing reactions which conserve sequences from the leader region and attach them to a suitable coding sequence."}
{"id": "PMID:222460", "title": "Immunoglobulin synthesis by lymphoid cells transformed in vitro by Abelson murine leukemia virus.", "content": "The majority of cell lines derived by infection of murine bone marrow cells with Abelson murine leukemia virus (A-MuLV) synthesize a mu chain but no detectable light chain. Aside from this mu-only phenotype, lines that make only light chain, both chains or no immunoglobulin-related polypeptides have also been found. Two lines have been studied in detail: one that makes only mu chain and one that makes only kappa light chain. Synthesis of both polypeptides can be increased by modifying the culture conditions so as to decrease the growth rate of the cells. Although some kappa chain secretion was observed, neither secreted nor surface mu was detected. We suggest that the mu- only phenotype may be an early normal step in the pathway of B lymphocyte maturation.", "contents": "Immunoglobulin synthesis by lymphoid cells transformed in vitro by Abelson murine leukemia virus. The majority of cell lines derived by infection of murine bone marrow cells with Abelson murine leukemia virus (A-MuLV) synthesize a mu chain but no detectable light chain. Aside from this mu-only phenotype, lines that make only light chain, both chains or no immunoglobulin-related polypeptides have also been found. Two lines have been studied in detail: one that makes only mu chain and one that makes only kappa light chain. Synthesis of both polypeptides can be increased by modifying the culture conditions so as to decrease the growth rate of the cells. Although some kappa chain secretion was observed, neither secreted nor surface mu was detected. We suggest that the mu- only phenotype may be an early normal step in the pathway of B lymphocyte maturation."}
{"id": "PMID:222461", "title": "A stretch of \"late\" SV40 viral DNA about 400 bp long which includes the origin of replication is specifically exposed in SV40 minichromosomes.", "content": "Examination of DNA fragments produced from either formaldehyde-fixed or unfixed SV40 minichromosomes by multiple-cut restriction endonucleases has led to the following major results: Exhaustive digestion of unfixed minichromosomes with Hae III generated all ten major limit-digest DNA fragments as well as partial cleavage products. In striking contrast to this result, Hae III acted on formaldehyde-fixed minichromosomes to yield only one of the limit-digest fragments, F, which is located in the immediate vicinity of the origin of replication, spanning nucleotides 5169 and 250 on the DNA sequence map of Reddy et al. (1978). This 300 base pair (bp) fragment was released as naked DNA from formaldehyde-fixed, Hae III-digested minichromosomes following treatment either by pronase-SDS or by SDS alone. In the latter case, the remainder of the minichromosome retained its compact configuration as assayed by both sedimentational and electrophoretic methods. In minichromosomes, the F fragment is therefore not only accessible to Hae III at its ends, but is also neither formaldehyde cross-linked into any SDS-resistant nucleoprotein structure nor topologically \"locked\" within the compact minichromosomal particle. This same fragment was preferentially produced during the early stages of digestion of unfixed minichromosomes with Hae III, and its final yield in the exhaustive Hae III digest was significantly higher than that of other limit-digest fragments. Similar results were obtained upon digestion of either unfixed or formaldehyde-fixed minichromosomes with Alu I. In particular, of approximately twenty major limit-digest DNA fragments, only two fragments (F and P, encompassing nucleotides 5146 to 190, and 190 to 325, respectively) were produced by Alu I from the formaldehyde-fixed minichromosomes. All other restriction endonucleases tested (Mbo I, Mbo II, Hind III, Hin II+III and Hinf I), for which there are no closely spaced recognition sequences in the above mentioned regions of the SV40 genome, did not produce any significant amount of limit-digest DNA fragments from formaldehyde-fixed minichromosomes. These findings, taken together with our earlier data on the preferential exposure of the origin of replication in SV40 minichromosomes (Varshavsky, Sundin and Bohn, 1978), strongly suggest that a specific region of the \"late\" SV40 DNA approximately 400 bp long is uniquely exposed in the compact minichromosome. It is of interest that, in addition to the origin of replication, this region contains binding sites for T antigen (Tjian, 1977), specific tandem repeated sequences and apparently also the promoters for synthesis of late SV40 mRNAs (Fiers et al., 1978; Reddy et al., 1978).", "contents": "A stretch of \"late\" SV40 viral DNA about 400 bp long which includes the origin of replication is specifically exposed in SV40 minichromosomes. Examination of DNA fragments produced from either formaldehyde-fixed or unfixed SV40 minichromosomes by multiple-cut restriction endonucleases has led to the following major results: Exhaustive digestion of unfixed minichromosomes with Hae III generated all ten major limit-digest DNA fragments as well as partial cleavage products. In striking contrast to this result, Hae III acted on formaldehyde-fixed minichromosomes to yield only one of the limit-digest fragments, F, which is located in the immediate vicinity of the origin of replication, spanning nucleotides 5169 and 250 on the DNA sequence map of Reddy et al. (1978). This 300 base pair (bp) fragment was released as naked DNA from formaldehyde-fixed, Hae III-digested minichromosomes following treatment either by pronase-SDS or by SDS alone. In the latter case, the remainder of the minichromosome retained its compact configuration as assayed by both sedimentational and electrophoretic methods. In minichromosomes, the F fragment is therefore not only accessible to Hae III at its ends, but is also neither formaldehyde cross-linked into any SDS-resistant nucleoprotein structure nor topologically \"locked\" within the compact minichromosomal particle. This same fragment was preferentially produced during the early stages of digestion of unfixed minichromosomes with Hae III, and its final yield in the exhaustive Hae III digest was significantly higher than that of other limit-digest fragments. Similar results were obtained upon digestion of either unfixed or formaldehyde-fixed minichromosomes with Alu I. In particular, of approximately twenty major limit-digest DNA fragments, only two fragments (F and P, encompassing nucleotides 5146 to 190, and 190 to 325, respectively) were produced by Alu I from the formaldehyde-fixed minichromosomes. All other restriction endonucleases tested (Mbo I, Mbo II, Hind III, Hin II+III and Hinf I), for which there are no closely spaced recognition sequences in the above mentioned regions of the SV40 genome, did not produce any significant amount of limit-digest DNA fragments from formaldehyde-fixed minichromosomes. These findings, taken together with our earlier data on the preferential exposure of the origin of replication in SV40 minichromosomes (Varshavsky, Sundin and Bohn, 1978), strongly suggest that a specific region of the \"late\" SV40 DNA approximately 400 bp long is uniquely exposed in the compact minichromosome. It is of interest that, in addition to the origin of replication, this region contains binding sites for T antigen (Tjian, 1977), specific tandem repeated sequences and apparently also the promoters for synthesis of late SV40 mRNAs (Fiers et al., 1978; Reddy et al., 1978)."}
{"id": "PMID:222463", "title": "Evolution of multiple genome mutations during long-term persistent infection by vesicular stomatitis virus.", "content": "Persistent infection of BHK21 cells was established with cloned vesicular somatitis virus plus purified Dl particles and maintained in vitro for over 5 years. After 1 year of persistence, the infectious virus RNA genome had evolved several oligonucleotide map changes, and numerous changes had accumulated by 3.5 years. Additional evolution occurred by the fourth year and continued until the fifth year. In contrast, repeated passage of virus in acute infections of several cell types in vitro or in vivo did not lead to detectable oligonucleotide map changes. The short Dl particle originally used to co-infect with infectious virus in establishing persistent infection has been displaced by an ever present and constantly changing population of other Dl particles of differing sizes and radically differing oligonucleotide maps. We conclude that the genomes of both infectious VSV and its Dl particles undergo continuous evolutionary change during years of persistence. In the infectious virus, these changes involve hundreds of mutations which are usually expressed as poorly replicating, temperature-sensitive, small plaque mutants. These are stable mutants which do not revert to wild-type when passaged repeatedly in acute infections at 37 or 33 degrees C. It appears that the sequestered intracellular environment of persistently infected cells favors rapid and continuous virus evolution.", "contents": "Evolution of multiple genome mutations during long-term persistent infection by vesicular stomatitis virus. Persistent infection of BHK21 cells was established with cloned vesicular somatitis virus plus purified Dl particles and maintained in vitro for over 5 years. After 1 year of persistence, the infectious virus RNA genome had evolved several oligonucleotide map changes, and numerous changes had accumulated by 3.5 years. Additional evolution occurred by the fourth year and continued until the fifth year. In contrast, repeated passage of virus in acute infections of several cell types in vitro or in vivo did not lead to detectable oligonucleotide map changes. The short Dl particle originally used to co-infect with infectious virus in establishing persistent infection has been displaced by an ever present and constantly changing population of other Dl particles of differing sizes and radically differing oligonucleotide maps. We conclude that the genomes of both infectious VSV and its Dl particles undergo continuous evolutionary change during years of persistence. In the infectious virus, these changes involve hundreds of mutations which are usually expressed as poorly replicating, temperature-sensitive, small plaque mutants. These are stable mutants which do not revert to wild-type when passaged repeatedly in acute infections at 37 or 33 degrees C. It appears that the sequestered intracellular environment of persistently infected cells favors rapid and continuous virus evolution."}
{"id": "PMID:222464", "title": "DNA sequence alterations in Hr-t deletion mutants of polyoma virus.", "content": "We have investigated the DNA sequence alterations in several hr-t mutants of polyoma virus. These mutants are defective in one of the two known viral functions essential for transformation and are altered with respect to several minor T antigen species. The lesions in some of these mutants have been mapped previously by marker rescue experiments to Hpa II fragment 4 (Hpa II-4, 78.4--91.7 map units) in the proximal part of the early region of the viral DNA. Thirteen of sixteen hr-t mutants examined carry deletions 2 to 5 map units (100--250 bp) long in Hpa 11-4. Three mutants carry either point mutations or very small deletions/insertions. Eight of the deletion mutants were mapped closely with restriction enzymes. Seven of them have deletions located entirely within the Hae III subfragment A of Hpa II-4 (the Hae A subfragment, 78.4--85.2 map units), and one extends just beyond this subfragment, ending at 85.5 map units. The complete sequence of the wild-type Hae A subfragment was determined and compared with those of four deletion mutants, NG-18, A-8, 6B5 and B-2. The deletion in each of these mutants is out-of-phase: NG-18, 187 bp; A-8, 127 bp; 6B-5, 179 bp; B-2, 241 bp. All are expected to remove protein sequences in the C terminal part of the small t antigen.", "contents": "DNA sequence alterations in Hr-t deletion mutants of polyoma virus. We have investigated the DNA sequence alterations in several hr-t mutants of polyoma virus. These mutants are defective in one of the two known viral functions essential for transformation and are altered with respect to several minor T antigen species. The lesions in some of these mutants have been mapped previously by marker rescue experiments to Hpa II fragment 4 (Hpa II-4, 78.4--91.7 map units) in the proximal part of the early region of the viral DNA. Thirteen of sixteen hr-t mutants examined carry deletions 2 to 5 map units (100--250 bp) long in Hpa 11-4. Three mutants carry either point mutations or very small deletions/insertions. Eight of the deletion mutants were mapped closely with restriction enzymes. Seven of them have deletions located entirely within the Hae III subfragment A of Hpa II-4 (the Hae A subfragment, 78.4--85.2 map units), and one extends just beyond this subfragment, ending at 85.5 map units. The complete sequence of the wild-type Hae A subfragment was determined and compared with those of four deletion mutants, NG-18, A-8, 6B5 and B-2. The deletion in each of these mutants is out-of-phase: NG-18, 187 bp; A-8, 127 bp; 6B-5, 179 bp; B-2, 241 bp. All are expected to remove protein sequences in the C terminal part of the small t antigen."}
{"id": "PMID:222465", "title": "Response of hemopoietic cells to avian acute leukemia viruses: effects on the differentiation of the target cells.", "content": "Chicken bone marrow cells were infected with three avian acute leukemia viruses (ALV)--avian myeloblastosis virus (AMV), myelocytomatosis virus strain MC29 and Mill Hill 2 virus (MH2)--and then cultured in agar in the presence of conditioned medium. Under these conditions, it was found that very few cells served as target cells for these three viruses. Density gradient separation showed that ALV target cells were found primarily in the light density fractions and might be represented by cells committed to the mononuclear phagocyte pathway. Separation of bone marrow cells on the basis of their sedimentation velocity at unit gravity suggested that MC29 and AMV did not share the same target cells. In addition, the analysis of surface receptors and functional markers characteristic of macrophages (Fc and complement receptors, phagocytosis and immune phagocytosis) indicated that the ALV-transformed cells were blocked during their differentiation. These results indicate that the transforming ability of ALV interferes with the differentiation of their target cells.", "contents": "Response of hemopoietic cells to avian acute leukemia viruses: effects on the differentiation of the target cells. Chicken bone marrow cells were infected with three avian acute leukemia viruses (ALV)--avian myeloblastosis virus (AMV), myelocytomatosis virus strain MC29 and Mill Hill 2 virus (MH2)--and then cultured in agar in the presence of conditioned medium. Under these conditions, it was found that very few cells served as target cells for these three viruses. Density gradient separation showed that ALV target cells were found primarily in the light density fractions and might be represented by cells committed to the mononuclear phagocyte pathway. Separation of bone marrow cells on the basis of their sedimentation velocity at unit gravity suggested that MC29 and AMV did not share the same target cells. In addition, the analysis of surface receptors and functional markers characteristic of macrophages (Fc and complement receptors, phagocytosis and immune phagocytosis) indicated that the ALV-transformed cells were blocked during their differentiation. These results indicate that the transforming ability of ALV interferes with the differentiation of their target cells."}
{"id": "PMID:222466", "title": "The fibronexus: a transmembrane association of fibronectin-containing fibers and bundles of 5 nm microfilaments in hamster and human fibroblasts.", "content": "A possible connection between external fibronectin-containing fibers and cytoplasmic 5 nm actin microfilaments within dense submembranous plaques has been observed by transmission electron microscopy. We refer to this transmembranous association as the fibronexus. Hamster embryo fibroblasts, transformed by wild-type or temperature-sensitive mutant (A28) SV40 virus, and human lung fibroblasts (WI-38, MRC-5) were studied using the tannic acid method of Simionescu and Simionescu (1976), which preferentially stained external carbohydrates. Fibronectin antigens were also localized on the extracellular fibers of the fibronexus with fibronectin antibody and immunoferritin staining. Goniometric studies of sections cut parallel to the plasmalemma demonstrated that the actin- and fibronectin-containing fibers of the fibronexus remained colinear when the specimen was tilted through a 40 degree angle about the fibrillar long axis. Sections cut perpendicular to the cell surface also showed that these fibers were apparently colinear. Our results suggest that the fibronectin and actin fibers of the fibronexus are closely associated (maximum separation distances of 8--22 nm), if not co-axial. Fibronexuses remained after expression of SV40-induced transformation, despite alteration of microfilament bundles and reduction in the amount of fibronectin (observed by immunofluorescence microscopy). The possible roles of fibronectin and the fibronexus in regulating actin polymerization are discussed.", "contents": "The fibronexus: a transmembrane association of fibronectin-containing fibers and bundles of 5 nm microfilaments in hamster and human fibroblasts. A possible connection between external fibronectin-containing fibers and cytoplasmic 5 nm actin microfilaments within dense submembranous plaques has been observed by transmission electron microscopy. We refer to this transmembranous association as the fibronexus. Hamster embryo fibroblasts, transformed by wild-type or temperature-sensitive mutant (A28) SV40 virus, and human lung fibroblasts (WI-38, MRC-5) were studied using the tannic acid method of Simionescu and Simionescu (1976), which preferentially stained external carbohydrates. Fibronectin antigens were also localized on the extracellular fibers of the fibronexus with fibronectin antibody and immunoferritin staining. Goniometric studies of sections cut parallel to the plasmalemma demonstrated that the actin- and fibronectin-containing fibers of the fibronexus remained colinear when the specimen was tilted through a 40 degree angle about the fibrillar long axis. Sections cut perpendicular to the cell surface also showed that these fibers were apparently colinear. Our results suggest that the fibronectin and actin fibers of the fibronexus are closely associated (maximum separation distances of 8--22 nm), if not co-axial. Fibronexuses remained after expression of SV40-induced transformation, despite alteration of microfilament bundles and reduction in the amount of fibronectin (observed by immunofluorescence microscopy). The possible roles of fibronectin and the fibronexus in regulating actin polymerization are discussed."}
{"id": "PMID:222469", "title": "Cellular regulation of mammalian sarcoma virus expression: a gene regulation model for oncogenesis.", "content": "Investigations aimed at defining cellular functions required for expression of transformation by mammalian sarcoma viruses have led to the isolation of a class of revertants that contain biologically active feline sarcoma virus, yet possess in vitro and in vivo properties of normal cells. The block to expression of the transformed state in these cellular revertants was spontaneously reversible at low frequency. Moreover, infection with certain helper viruses reversed the block at very high efficiency. Helper virus complementation was shown not to be a direct effect of helper virus functions expressed in the initially infected revertant cell. Rather, the helper virus acted indirectly by rescuing sarcoma virus and allowing it to infect and transform another cell within the revertant population. Using biochemical and immunologic techniques, it was possible to demonstrate a specific and very marked reduction in transcriptional and translational products of the sarcoma viral genome in the revertant cells. Findings that the reversal of this block was associated with reacquisition of the transformed phenotype, together with other evidence, suggest that reversion results from cellular transcriptional regulation of the integrated sarcoma virus genome. Reversion in this virus transformation system provides a model for oncogenesis resulting from derepression of cellular genes that possess malignant potential.", "contents": "Cellular regulation of mammalian sarcoma virus expression: a gene regulation model for oncogenesis. Investigations aimed at defining cellular functions required for expression of transformation by mammalian sarcoma viruses have led to the isolation of a class of revertants that contain biologically active feline sarcoma virus, yet possess in vitro and in vivo properties of normal cells. The block to expression of the transformed state in these cellular revertants was spontaneously reversible at low frequency. Moreover, infection with certain helper viruses reversed the block at very high efficiency. Helper virus complementation was shown not to be a direct effect of helper virus functions expressed in the initially infected revertant cell. Rather, the helper virus acted indirectly by rescuing sarcoma virus and allowing it to infect and transform another cell within the revertant population. Using biochemical and immunologic techniques, it was possible to demonstrate a specific and very marked reduction in transcriptional and translational products of the sarcoma viral genome in the revertant cells. Findings that the reversal of this block was associated with reacquisition of the transformed phenotype, together with other evidence, suggest that reversion results from cellular transcriptional regulation of the integrated sarcoma virus genome. Reversion in this virus transformation system provides a model for oncogenesis resulting from derepression of cellular genes that possess malignant potential."}
{"id": "PMID:222470", "title": "Regulation of corneal collagenase production: stimulation of serially passaged stromal cells by blood mononuclear cells.", "content": "After three or more passages, stromal cell outgrowths from explants of normal rabbit corneas and from corneas previously burned with alkali did not produce collagenase until they were stimulated by the addition of rabbit blood-derived mononuclear cells or media conditioned by them. Normal stromal cells required stimulation by lymphocytes or their products from alkali-burned animals, whereas those from alkali-burned corneas were stimulated by lymphocytes from either normal or alkali-burned rabbits.", "contents": "Regulation of corneal collagenase production: stimulation of serially passaged stromal cells by blood mononuclear cells. After three or more passages, stromal cell outgrowths from explants of normal rabbit corneas and from corneas previously burned with alkali did not produce collagenase until they were stimulated by the addition of rabbit blood-derived mononuclear cells or media conditioned by them. Normal stromal cells required stimulation by lymphocytes or their products from alkali-burned animals, whereas those from alkali-burned corneas were stimulated by lymphocytes from either normal or alkali-burned rabbits."}
{"id": "PMID:222471", "title": "Karyologically identified homozygous tw18 embryos: extrauterine growth properties and transformation by SV40.", "content": "A method for identifying individual embryos from crosses segregating homozygous t lethals using the marker chromosome Rb7 is described and applied to the tw18 haplotype. In contrast to wild-type and heterozygous littermates, homozygous tw18/tw18 6 and 8 day embryos have very limited growth potentialities in vitro. When transplanted under the testis capsule, homozygous tw18 embryos (3, 6 and 7 day) produce teratomas at a much lower efficiency than heterozygous and wild-type embryos, and the rare teratomas thus obtained have limited growth potentialities when cultured in vitro. Upon transformation with SV40, however, permanent lines of cells of mesodermal origin, capable of myoblastic or adipocytic differentiation, have been obtained. This shows that the effect of the mutation on cell growth can be overcome by SV40 transformation.", "contents": "Karyologically identified homozygous tw18 embryos: extrauterine growth properties and transformation by SV40. A method for identifying individual embryos from crosses segregating homozygous t lethals using the marker chromosome Rb7 is described and applied to the tw18 haplotype. In contrast to wild-type and heterozygous littermates, homozygous tw18/tw18 6 and 8 day embryos have very limited growth potentialities in vitro. When transplanted under the testis capsule, homozygous tw18 embryos (3, 6 and 7 day) produce teratomas at a much lower efficiency than heterozygous and wild-type embryos, and the rare teratomas thus obtained have limited growth potentialities when cultured in vitro. Upon transformation with SV40, however, permanent lines of cells of mesodermal origin, capable of myoblastic or adipocytic differentiation, have been obtained. This shows that the effect of the mutation on cell growth can be overcome by SV40 transformation."}
{"id": "PMID:222472", "title": "Cross-linking of fibronectin to sulfated proteoglycans at the cell surface.", "content": "Fibronectin is a major surface protein of normal animal cells but is absent from many transformed cells. Addition of fibronectin to transformed cells causes increased cell substrate adhesion and changes in the morphology and cytoskeleton of the cells. We have coupled fibronectin to photoactivable chemical cross-linkers and have added it to cells to identify those molecules to which it binds. In this way, fibronectin can be cross-linked to sulfated proteoglycans at the cell surface. The cross-linking is specific for fibronectin. The fibronectin-proteoglycan complex is sensitive to chondroitinase ABC and AC and to trypsin. Addition of fibronectin also affects binding of hyaluronic acid to the cells. These results suggest that fibronectin interacts with proteoglycans at the cell surface. The existence of such interactions may have implications for the role of fibronectin and proteoglycans in cell adhesion.", "contents": "Cross-linking of fibronectin to sulfated proteoglycans at the cell surface. Fibronectin is a major surface protein of normal animal cells but is absent from many transformed cells. Addition of fibronectin to transformed cells causes increased cell substrate adhesion and changes in the morphology and cytoskeleton of the cells. We have coupled fibronectin to photoactivable chemical cross-linkers and have added it to cells to identify those molecules to which it binds. In this way, fibronectin can be cross-linked to sulfated proteoglycans at the cell surface. The cross-linking is specific for fibronectin. The fibronectin-proteoglycan complex is sensitive to chondroitinase ABC and AC and to trypsin. Addition of fibronectin also affects binding of hyaluronic acid to the cells. These results suggest that fibronectin interacts with proteoglycans at the cell surface. The existence of such interactions may have implications for the role of fibronectin and proteoglycans in cell adhesion."}
{"id": "PMID:222473", "title": "Spontaneous glycosylation of glycosaminoglycan substrates by adherent fibroblasts.", "content": "SV40-transformed mouse fibroblasts migrate upon, and spontaneously glycosylate, plastic substrates derivatized with chondroitin-6 sulfate and hyaluronic acid. Autoradiography of cultures prelabeled with 3H-glucose and 3H-galactose demonstrates the presence of silver grains near adherent cells. Silver grains are particularly dense near cells cultured on chondroitin sulfate. No significant grains are observed on control dishes or dishes derivatized with polygalacturonic acid. Radioactive material left by cells is not removed by boiling the dishes in 8 M urea and 10% sodium dodecylsulfate, suggesting that it is covalently linked to the derivatized plastic. Acid hydrolysis shows that the radioactive material consists of glucuronic acid and N-acetylglucosamine when the prelabeled cells are cultured on hyaluronic acid. When cells are cultured on chondroitin sulfate, the radioactive product consists only of glucuronic and and N-acetylgalactosamine sulfate. Sonicates of prelabeled cells or the supernatants from cultures of intact prelabeled cells add no SDS-urea-resistant radioactivity to dishes derivatized with these glycosaminoglycans.", "contents": "Spontaneous glycosylation of glycosaminoglycan substrates by adherent fibroblasts. SV40-transformed mouse fibroblasts migrate upon, and spontaneously glycosylate, plastic substrates derivatized with chondroitin-6 sulfate and hyaluronic acid. Autoradiography of cultures prelabeled with 3H-glucose and 3H-galactose demonstrates the presence of silver grains near adherent cells. Silver grains are particularly dense near cells cultured on chondroitin sulfate. No significant grains are observed on control dishes or dishes derivatized with polygalacturonic acid. Radioactive material left by cells is not removed by boiling the dishes in 8 M urea and 10% sodium dodecylsulfate, suggesting that it is covalently linked to the derivatized plastic. Acid hydrolysis shows that the radioactive material consists of glucuronic acid and N-acetylglucosamine when the prelabeled cells are cultured on hyaluronic acid. When cells are cultured on chondroitin sulfate, the radioactive product consists only of glucuronic and and N-acetylgalactosamine sulfate. Sonicates of prelabeled cells or the supernatants from cultures of intact prelabeled cells add no SDS-urea-resistant radioactivity to dishes derivatized with these glycosaminoglycans."}
{"id": "PMID:222474", "title": "Phorbol ester-induced morphological changes in transformed chick fibroblasts: evidence for direct catalytic involvement of plasminogen activator.", "content": "The tumor promoter phorbol myristate acetate (PMA) induces the production of the serine protease plasminogen activator (PA) in cultures of normal chick embryo fibroblasts (CEF) and synergistically enhances PA production in Rous sarcoma virus-transformed chick embryo fibroblasts (RSVCEF). Following PMA treatment of serum-free RSVCEF cultures, PA induction is accompanied by distinct morphological changes, including enhanced cell clustering and the formation of dense cellular aggregates. These alterations in the morphology of the PMA-treated transformed cells are inhibited by several protease inhibitors, including leupeptin, NPGB, SBTI, benzamidine and DFP, the specific inhibitor of serine enzymes. A number of protease inhibitors are ineffective in preventing the PMA-induced morphological changes; these include inhibitors of trypsin, chymotrypsin, elastase, thrombin and, most importantly, plasmin. The use of a fluorescent substrate to assay PA directly demonstrated that the pattern of inhibiton of PA activity correlates exactly with the inhibition of morphological changes. The of 3H-DFP to label and characterize serine zymes in the culture fluid from PMA-treated cells further indicated that PA is the serine protease responsible for the morphological changes. Thus PA itself can catalytically alter cellular behavior in culture independent of plasminogen, until not its only known natural substrate.", "contents": "Phorbol ester-induced morphological changes in transformed chick fibroblasts: evidence for direct catalytic involvement of plasminogen activator. The tumor promoter phorbol myristate acetate (PMA) induces the production of the serine protease plasminogen activator (PA) in cultures of normal chick embryo fibroblasts (CEF) and synergistically enhances PA production in Rous sarcoma virus-transformed chick embryo fibroblasts (RSVCEF). Following PMA treatment of serum-free RSVCEF cultures, PA induction is accompanied by distinct morphological changes, including enhanced cell clustering and the formation of dense cellular aggregates. These alterations in the morphology of the PMA-treated transformed cells are inhibited by several protease inhibitors, including leupeptin, NPGB, SBTI, benzamidine and DFP, the specific inhibitor of serine enzymes. A number of protease inhibitors are ineffective in preventing the PMA-induced morphological changes; these include inhibitors of trypsin, chymotrypsin, elastase, thrombin and, most importantly, plasmin. The use of a fluorescent substrate to assay PA directly demonstrated that the pattern of inhibiton of PA activity correlates exactly with the inhibition of morphological changes. The of 3H-DFP to label and characterize serine zymes in the culture fluid from PMA-treated cells further indicated that PA is the serine protease responsible for the morphological changes. Thus PA itself can catalytically alter cellular behavior in culture independent of plasminogen, until not its only known natural substrate."}
{"id": "PMID:222475", "title": "Characterization of a 54K dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells.", "content": "SV40 infection or transformation of murine cells stimulated the production of a 54K dalton protein that was specifically immunoprecipitated, along with SV40 large T and small t antigens, with sera from mice or hamsters bearing SV40-induced tumors. The same SV40 anti-T sera immunoprecipitated a 54K dalton protein from two different, uninfected murine embryonal carcinoma cell lines. These 54K proteins from SV40-transformed mouse cells and the uninfected embryonal carcinomas cells had identical partial peptide maps which were completely different from the partial peptide map of SV40 large T antigen. An Ad2+ND4-transformed hamster cell line also expressed a 54K protein that was specifically immunoprecipitated by SV40 T sera. The partial peptide maps of the mouse and hamster 54K protein were different, showing the host cell species specificity of these proteins. The 54K hamster protein was also unrelated to the Ad2+ND4 SV40 T antigen. Analogous proteins immunoprecipitated by SV40 T sera, ranging in molecular weight from 44K to 60K, were detected in human and monkey SV40-infected or -transformed cells. A wide variety of sera from hamsters and mice bearing SV40-induced tumors immunoprecipitated the 54K protein of SV40-transformed cells and murine embryonal carcinoma cells. Antibody produced by somatic cell hybrids between a B cell and a myeloma cell (hybridoma) against SV40 large T antigen also immunoprecipitated the 54K protein in virus-infected and -transformed cells, but did not do so in the embryonal carcinoma cell lines. We conclude that SV40 infection or transformation of mouse cells stimulates the synthesis or enhances the stability of a 54K protein. This protein appears to be associated with SV40 T antigen in SV40-infected and -transformed cells, and is co-immunoprecipitated by hybridomas sera to SV40 large T antigen. The 54K protein either shares antigenic determinants with SV40 T antigen or is itself immunogenic when in association with SV40 large T antigen. The protein varies with host cell species, and analogous proteins were observed in hamster,  monkey and human cells. The role of this protein in transformation is unclear at present.", "contents": "Characterization of a 54K dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells. SV40 infection or transformation of murine cells stimulated the production of a 54K dalton protein that was specifically immunoprecipitated, along with SV40 large T and small t antigens, with sera from mice or hamsters bearing SV40-induced tumors. The same SV40 anti-T sera immunoprecipitated a 54K dalton protein from two different, uninfected murine embryonal carcinoma cell lines. These 54K proteins from SV40-transformed mouse cells and the uninfected embryonal carcinomas cells had identical partial peptide maps which were completely different from the partial peptide map of SV40 large T antigen. An Ad2+ND4-transformed hamster cell line also expressed a 54K protein that was specifically immunoprecipitated by SV40 T sera. The partial peptide maps of the mouse and hamster 54K protein were different, showing the host cell species specificity of these proteins. The 54K hamster protein was also unrelated to the Ad2+ND4 SV40 T antigen. Analogous proteins immunoprecipitated by SV40 T sera, ranging in molecular weight from 44K to 60K, were detected in human and monkey SV40-infected or -transformed cells. A wide variety of sera from hamsters and mice bearing SV40-induced tumors immunoprecipitated the 54K protein of SV40-transformed cells and murine embryonal carcinoma cells. Antibody produced by somatic cell hybrids between a B cell and a myeloma cell (hybridoma) against SV40 large T antigen also immunoprecipitated the 54K protein in virus-infected and -transformed cells, but did not do so in the embryonal carcinoma cell lines. We conclude that SV40 infection or transformation of mouse cells stimulates the synthesis or enhances the stability of a 54K protein. This protein appears to be associated with SV40 T antigen in SV40-infected and -transformed cells, and is co-immunoprecipitated by hybridomas sera to SV40 large T antigen. The 54K protein either shares antigenic determinants with SV40 T antigen or is itself immunogenic when in association with SV40 large T antigen. The protein varies with host cell species, and analogous proteins were observed in hamster,  monkey and human cells. The role of this protein in transformation is unclear at present."}
{"id": "PMID:222476", "title": "AKR leukemogenesis: identification and biological significance of thymic lymphoma receptors for AKR retroviruses.", "content": "We have previously demonstrated that in vitro cell lines of mouse thymic lymphomas express surface receptors specific for the retrovirus that induced them. This study extends these observations to an analysis of receptor-bearing cells in the preleukemic and leukemic phases of spontaneous AKR thymic lymphomagenesis. AKR mice regularly begin expressing N-tropic retroviruses (as assayed on NIH fibroblasts by the XC plaque assay) in several tissues early in life; thymic lymphocytes also express these viruses, but are not autonomously transformed. Later thymic lymphomas emerge which are capable of metastasizing in the host of origin or transplanting leukemias into syngeneic hosts. Just prior to the appearance of thymic lymphomas, these mice also begin producing xenotropic retroviruses [as assayed in xenogeneic (For example, mink) fibroblasts], and concomitant with the appearance of the leukemias is the appearance of \"recombinant\" retroviruses which cause mink fibroblast foci (MCF); these viruses express elements of both N- and X-tropic virus envelopes and N-tropic viral gene products in their cores. Spontaneous AKR leukemias also produce other retroviruses which do not cause XC plaques or mink fibroblast foci; these are called SL viruses. The subject of this study was to test whether in vivo thymocytes in the preleukemic and leukemic periods also bear receptors specific for N-tropic, recombinant MCF and SL AKR retroviruses. We demonstrated that each spontaneous thymic lymphoma does bear receptors that bind viruses produced by the lymphomas and MCF-247 to a high degree and that bind N-ecotropic AKR retroviruses less well. Thymic lymphocytes predominating in the preleukemic period do not express detectable levels of receptors for either of the viruses. In some mice, receptor-positive cells co-exist with receptor-negative cells; only the receptor-positive cells are capable of transplanting leukemia to syngeneic hosts. We conclude that the presence of specific cell surface receptors for lymphoma cell-produced and recombinant AKR retroviruses is a marker for leukemia in these hosts.", "contents": "AKR leukemogenesis: identification and biological significance of thymic lymphoma receptors for AKR retroviruses. We have previously demonstrated that in vitro cell lines of mouse thymic lymphomas express surface receptors specific for the retrovirus that induced them. This study extends these observations to an analysis of receptor-bearing cells in the preleukemic and leukemic phases of spontaneous AKR thymic lymphomagenesis. AKR mice regularly begin expressing N-tropic retroviruses (as assayed on NIH fibroblasts by the XC plaque assay) in several tissues early in life; thymic lymphocytes also express these viruses, but are not autonomously transformed. Later thymic lymphomas emerge which are capable of metastasizing in the host of origin or transplanting leukemias into syngeneic hosts. Just prior to the appearance of thymic lymphomas, these mice also begin producing xenotropic retroviruses [as assayed in xenogeneic (For example, mink) fibroblasts], and concomitant with the appearance of the leukemias is the appearance of \"recombinant\" retroviruses which cause mink fibroblast foci (MCF); these viruses express elements of both N- and X-tropic virus envelopes and N-tropic viral gene products in their cores. Spontaneous AKR leukemias also produce other retroviruses which do not cause XC plaques or mink fibroblast foci; these are called SL viruses. The subject of this study was to test whether in vivo thymocytes in the preleukemic and leukemic periods also bear receptors specific for N-tropic, recombinant MCF and SL AKR retroviruses. We demonstrated that each spontaneous thymic lymphoma does bear receptors that bind viruses produced by the lymphomas and MCF-247 to a high degree and that bind N-ecotropic AKR retroviruses less well. Thymic lymphocytes predominating in the preleukemic period do not express detectable levels of receptors for either of the viruses. In some mice, receptor-positive cells co-exist with receptor-negative cells; only the receptor-positive cells are capable of transplanting leukemia to syngeneic hosts. We conclude that the presence of specific cell surface receptors for lymphoma cell-produced and recombinant AKR retroviruses is a marker for leukemia in these hosts."}
{"id": "PMID:222477", "title": "The introduction of poliovirus RNA into cells via lipid vesicles (liposomes).", "content": "Large unilamellar vesicles (LUV) composed of phosphatidylserine are capable of encapsulating poliovirus ribonucleic acid (RNA) and delivering it efficiently to cells in an infectious form. The biological activity of vesicle-entrapped poliovirus RNA was 1-2 x 10(4) plaque forming units/nanogram (pfu/ng) and appeared to be enhanced by ribonuclease treatment of the vesicle preparations (infectivity = 1-2 x 10(5) pfu/ng). Vesicle-mediated RNA infection produced equivalent titers in primate and nonprimate cells. Moreover, the data strongly suggest that the ratio of molecules per infectious unit is close to one when the RNA is properly delivered to the cell. A comparative study of LUV and multilamellar vesicles (MLV) indicates that LUV deliver their contents to the cell cytoplasm much more efficiently than MLV. LUV-entrapped poliovirus RNA produced infectious titer 10-100 fold higher than comparable RNA preparations delivered to cells by other techniques.", "contents": "The introduction of poliovirus RNA into cells via lipid vesicles (liposomes). Large unilamellar vesicles (LUV) composed of phosphatidylserine are capable of encapsulating poliovirus ribonucleic acid (RNA) and delivering it efficiently to cells in an infectious form. The biological activity of vesicle-entrapped poliovirus RNA was 1-2 x 10(4) plaque forming units/nanogram (pfu/ng) and appeared to be enhanced by ribonuclease treatment of the vesicle preparations (infectivity = 1-2 x 10(5) pfu/ng). Vesicle-mediated RNA infection produced equivalent titers in primate and nonprimate cells. Moreover, the data strongly suggest that the ratio of molecules per infectious unit is close to one when the RNA is properly delivered to the cell. A comparative study of LUV and multilamellar vesicles (MLV) indicates that LUV deliver their contents to the cell cytoplasm much more efficiently than MLV. LUV-entrapped poliovirus RNA produced infectious titer 10-100 fold higher than comparable RNA preparations delivered to cells by other techniques."}
{"id": "PMID:222478", "title": "E. coli DNA binding protein HU forms nucleosomelike structure with circular double-stranded DNA.", "content": "The incubation of the E coli DNA binding protein HU with relaxed circular SV40 DNA in the presence of pure nicking-closing enzyme introduces up to 18 negative superhelical turns in the DNA molecules as measured by agarose gel electrophoresis. The maximal density of supercoiling is obtained at a HU-DNA mass ratio of 1. Reconstituted DNA-HU complexes prefixed with glutaraldehyde appear as condensed circular structures having an average of 14 \"beads\" per circular SV40 DNA molecule, with a \"bead\" diameter of 180 +/- 23 A. The circular SV40 DNA is condensed by a ratio of 2.0-2.5 relative to naked DNA. This is similar to the ratio (2.4) measured for chromatin formed by reassociation of relaxed SV40 DNA with the four core histones.", "contents": "E. coli DNA binding protein HU forms nucleosomelike structure with circular double-stranded DNA. The incubation of the E coli DNA binding protein HU with relaxed circular SV40 DNA in the presence of pure nicking-closing enzyme introduces up to 18 negative superhelical turns in the DNA molecules as measured by agarose gel electrophoresis. The maximal density of supercoiling is obtained at a HU-DNA mass ratio of 1. Reconstituted DNA-HU complexes prefixed with glutaraldehyde appear as condensed circular structures having an average of 14 \"beads\" per circular SV40 DNA molecule, with a \"bead\" diameter of 180 +/- 23 A. The circular SV40 DNA is condensed by a ratio of 2.0-2.5 relative to naked DNA. This is similar to the ratio (2.4) measured for chromatin formed by reassociation of relaxed SV40 DNA with the four core histones."}
{"id": "PMID:222479", "title": "A murine sarcoma virus-associated protein kinase: interaction with actin and microtubular protein.", "content": "A low molecular weight (LMW) protein phosphokinase enzyme that binds to actin has been isolated from murine sarcoma virions; this kinase activity is not present in nontransforming murine leukemia viruses. Sephadex G-75 gel filtration and affinity chromatography on actin-Sepharose conjugates allow a significant level of purification of this enzyme. The enzyme associates with microtubular proteins and inhibits the in vitro polymerization of microtubules. This study represents the first isolation of a sarcoma virus-associated protein that possesses the ability to interact directly with two major components of the cytoskeletal system.", "contents": "A murine sarcoma virus-associated protein kinase: interaction with actin and microtubular protein. A low molecular weight (LMW) protein phosphokinase enzyme that binds to actin has been isolated from murine sarcoma virions; this kinase activity is not present in nontransforming murine leukemia viruses. Sephadex G-75 gel filtration and affinity chromatography on actin-Sepharose conjugates allow a significant level of purification of this enzyme. The enzyme associates with microtubular proteins and inhibits the in vitro polymerization of microtubules. This study represents the first isolation of a sarcoma virus-associated protein that possesses the ability to interact directly with two major components of the cytoskeletal system."}
{"id": "PMID:222480", "title": "Sequence from early region of polyoma virus DNA containing viral replication origin and encoding small, middle and (part of) large T antigens.", "content": "The sequence of about one third of the polyoma virus genome is presented. This sequence covers the origin of replication of two large plaque strains (A2 and A3) of polyoma virus. The two strains differ by 11 bp in the origin region. A model for replication is suggested. The sequence probably also covers the entire coding region of two of the polyoma virus early proteins--small and middle T antigens--as well as part of the coding region for large T antigen. Over a small region of the DNA, all three coding frames contain termination codons, which argues a need for spliced early messenger RNAs. In another region of the DNA, two coding frames can be used. Correlation with protein data suggests that one frame codes for part of middle T antigen and the other for part of large T antigen.", "contents": "Sequence from early region of polyoma virus DNA containing viral replication origin and encoding small, middle and (part of) large T antigens. The sequence of about one third of the polyoma virus genome is presented. This sequence covers the origin of replication of two large plaque strains (A2 and A3) of polyoma virus. The two strains differ by 11 bp in the origin region. A model for replication is suggested. The sequence probably also covers the entire coding region of two of the polyoma virus early proteins--small and middle T antigens--as well as part of the coding region for large T antigen. Over a small region of the DNA, all three coding frames contain termination codons, which argues a need for spliced early messenger RNAs. In another region of the DNA, two coding frames can be used. Correlation with protein data suggests that one frame codes for part of middle T antigen and the other for part of large T antigen."}
{"id": "PMID:222481", "title": "Neural crest cells: temperature-dependent transformation by Rous sarcoma virus.", "content": "Cranial neural crest cells from chick embryos, when cultured under appropriate conditions, differentiate after approx. 1 week into pigmented cells. Neurol crest cells were infested with a mutant (RSV-BH-Ta) of the Bryan 'high titer' strain of Rous sarcoma virus on the second day of culture before the cells were morphologically differentiated, or later after they became pigmented. Cells infected and maintained at the temperature permissive for transformation (37 degrees C) proliferated rapidly compared to uninfected cells are produced extensive cytoplasmic vacuoles in a fashion similar to other types of cells transformed with RSV-BH-Ta at 37 degrees C. Cells infected and maintained at the non-permissive temperature for transformation (41 degrees C) also proliferated rapidly but did not become morphologically transformed. Transformation occurred reversibly following a shift of temperature. Infection of morphologically undifferentiated neural crest cells at either temperature prevented their differentiation into pigment cells, and infection of pigmented neural crest cells at either temperature led to a gradual loss of pigmentation. These results suggest that even at the non-permissive temperature the virus may regulate the state of differentiation of certain types of cells.", "contents": "Neural crest cells: temperature-dependent transformation by Rous sarcoma virus. Cranial neural crest cells from chick embryos, when cultured under appropriate conditions, differentiate after approx. 1 week into pigmented cells. Neurol crest cells were infested with a mutant (RSV-BH-Ta) of the Bryan 'high titer' strain of Rous sarcoma virus on the second day of culture before the cells were morphologically differentiated, or later after they became pigmented. Cells infected and maintained at the temperature permissive for transformation (37 degrees C) proliferated rapidly compared to uninfected cells are produced extensive cytoplasmic vacuoles in a fashion similar to other types of cells transformed with RSV-BH-Ta at 37 degrees C. Cells infected and maintained at the non-permissive temperature for transformation (41 degrees C) also proliferated rapidly but did not become morphologically transformed. Transformation occurred reversibly following a shift of temperature. Infection of morphologically undifferentiated neural crest cells at either temperature prevented their differentiation into pigment cells, and infection of pigmented neural crest cells at either temperature led to a gradual loss of pigmentation. These results suggest that even at the non-permissive temperature the virus may regulate the state of differentiation of certain types of cells."}
{"id": "PMID:222482", "title": "Modifications of the activities of key enzymes and intracellular levels of cyclic nucleotides, in correlation with the glyogen deposition in a cultured hepatoma cell line.", "content": "Glycogen accumulation in growing cultures of ZHC cells (originally derived from the Zajdela ascitic hepatoma) is accompanied by an increase in glycogen synthetase (E.C. 2.4.1.11) and phosphorylase (E.C. 2.4.1.1) activities. Essentially the synthetase b and the phosphorylase a are involved in this process. The glycogen accumulation in ZHC cells us preceeded by a noticeable peak of cAMP, whereas cGMP rises early after replating and then decreases simultaneously with the growth rate. The present results suggest that these cultured hepatoma cells undergo throughout every passage an induction process involved in glycogen synthesis storage. Since the original ascites cells growing in vivo (which lack glycogen) and the cultured ZHC cells exhibit similar glycogen synthetase and phosphorylase activities, the resurgence of the glycogenic function (Staedel and Beck, 1978) in the in vitro cultureed cells does not seem related to a change in these two enzymes. By contrast, the high cyclic nucleotide levels in the cultured cells, as compared to those in the ascites cells, offer a possible explanation.", "contents": "Modifications of the activities of key enzymes and intracellular levels of cyclic nucleotides, in correlation with the glyogen deposition in a cultured hepatoma cell line. Glycogen accumulation in growing cultures of ZHC cells (originally derived from the Zajdela ascitic hepatoma) is accompanied by an increase in glycogen synthetase (E.C. 2.4.1.11) and phosphorylase (E.C. 2.4.1.1) activities. Essentially the synthetase b and the phosphorylase a are involved in this process. The glycogen accumulation in ZHC cells us preceeded by a noticeable peak of cAMP, whereas cGMP rises early after replating and then decreases simultaneously with the growth rate. The present results suggest that these cultured hepatoma cells undergo throughout every passage an induction process involved in glycogen synthesis storage. Since the original ascites cells growing in vivo (which lack glycogen) and the cultured ZHC cells exhibit similar glycogen synthetase and phosphorylase activities, the resurgence of the glycogenic function (Staedel and Beck, 1978) in the in vitro cultureed cells does not seem related to a change in these two enzymes. By contrast, the high cyclic nucleotide levels in the cultured cells, as compared to those in the ascites cells, offer a possible explanation."}
{"id": "PMID:222487", "title": "Ca2+-binding modulator protein in protozoa and myxomycete.", "content": "Ca2+-binding protein with the properties of brain modulator protein of 3,5-cyclic nucleotide phosphodiesterase was identified in Physarum polycephalum plasmodia and in Euglena gracilis and Amoeba proteus cells by urea polyacrylamide gel electrophoresis and activation of cyclic nucleotide phosphodiesterase and of myosin light chain kinase.", "contents": "Ca2+-binding modulator protein in protozoa and myxomycete. Ca2+-binding protein with the properties of brain modulator protein of 3,5-cyclic nucleotide phosphodiesterase was identified in Physarum polycephalum plasmodia and in Euglena gracilis and Amoeba proteus cells by urea polyacrylamide gel electrophoresis and activation of cyclic nucleotide phosphodiesterase and of myosin light chain kinase."}
{"id": "PMID:222488", "title": "A comparision of normal submaxillary gland proteins with proteins obtained from a transplantable murine salivary gland carcinoma (myoepithelioma).", "content": "A new transplantable murine salivary gland carcinoma (myoepithelioma) was further characterized by comparing total protein patterns with normal submaxillary gland proteins. Analysis by isoelectric focussing or by labelling studies with radioactive leucine showed considerable differences between tumour and normal proteins. In contrast, analysis of staining patterns after electrophoresis in sodium dodecyl sulphate containing gels revealed a striking similarity between normal proteins, tumour proteins and proteins obtained from metastatic growths. It thus appears that tumour proteins closely resemble the normal proteins from the tissue of origin with respect to molecular size as determined by electrophoretic mobility, while significant differences occur in charge and labelling kinetics.", "contents": "A comparision of normal submaxillary gland proteins with proteins obtained from a transplantable murine salivary gland carcinoma (myoepithelioma). A new transplantable murine salivary gland carcinoma (myoepithelioma) was further characterized by comparing total protein patterns with normal submaxillary gland proteins. Analysis by isoelectric focussing or by labelling studies with radioactive leucine showed considerable differences between tumour and normal proteins. In contrast, analysis of staining patterns after electrophoresis in sodium dodecyl sulphate containing gels revealed a striking similarity between normal proteins, tumour proteins and proteins obtained from metastatic growths. It thus appears that tumour proteins closely resemble the normal proteins from the tissue of origin with respect to molecular size as determined by electrophoretic mobility, while significant differences occur in charge and labelling kinetics."}
{"id": "PMID:222489", "title": "Selective effects of trypsinization on established and tumour-derived mouse 3T3 cells.", "content": "Explanted tumour cells are much more sensitive to the deleterious effects of routine trypsinization than are the parent 3T3 or SV40 transformed established cell lines. This differential sensitivity causes the disappearance of tumour-derived cells when grown in co-culture with untransformed 3T3 cells and accounts in some tumor explants for the emergence of trypsin-resistant varient cells which have lost tumour-specific properties.", "contents": "Selective effects of trypsinization on established and tumour-derived mouse 3T3 cells. Explanted tumour cells are much more sensitive to the deleterious effects of routine trypsinization than are the parent 3T3 or SV40 transformed established cell lines. This differential sensitivity causes the disappearance of tumour-derived cells when grown in co-culture with untransformed 3T3 cells and accounts in some tumor explants for the emergence of trypsin-resistant varient cells which have lost tumour-specific properties."}
{"id": "PMID:222490", "title": "Oscillating contractions in protoplasmic strands of Physarum: effects of externally applied ouabain, sodium-, potassium- and calcium-ions.", "content": "1. Concentrations of 0.1-10 mM Ouabain do not affect oscillating contractions, when applied externally in physiological solutions. 2. Ouabain has no effect, when applied in solutions of increased sodium- (100 mM) and lowered potassium-concentration (0.1 or zero mM). 3. De novo generation of oscillating contractions in protoplasmic drops is not suppressed in Ouabain-solutions. 4. Biochemical studies of Na-K-ATPase did not show any Ouabain sensitive ATPase-activity. 5. Reaction of veins on high concentrations (300 mosm) is discussed as to be a physical effect. 6. It is concluded that no Na-K-ATPase is engaged in triggering oscillating contraction automaticity.", "contents": "Oscillating contractions in protoplasmic strands of Physarum: effects of externally applied ouabain, sodium-, potassium- and calcium-ions. 1. Concentrations of 0.1-10 mM Ouabain do not affect oscillating contractions, when applied externally in physiological solutions. 2. Ouabain has no effect, when applied in solutions of increased sodium- (100 mM) and lowered potassium-concentration (0.1 or zero mM). 3. De novo generation of oscillating contractions in protoplasmic drops is not suppressed in Ouabain-solutions. 4. Biochemical studies of Na-K-ATPase did not show any Ouabain sensitive ATPase-activity. 5. Reaction of veins on high concentrations (300 mosm) is discussed as to be a physical effect. 6. It is concluded that no Na-K-ATPase is engaged in triggering oscillating contraction automaticity."}
{"id": "PMID:222491", "title": "SV40 DNA injected into Xenopus oocyte nuclei is transcribed by RNA polymerase B.", "content": "SV40 DNA I. injected into Xenopus oocyte nuclei is transcribed. The SV40-specific RNA molecules migrate on sucrose gradients as do viral RNAs formed in infected green monkey cells but a variable proportion of RNA sequences complementary to SV40 DNA is also found in the light region of the gradients. All SV40-specific RNA species seem to be synthesized by RNA polymerase B as their synthesis is completely sensitive to low concentrations (0.1 microgram/ml) of alpha-amanitin. Concomittantly, the formation of SV40-specific proteins (tumor antigens) is inhibited by injecting alpha-amanitin together with the SV40 DNA.", "contents": "SV40 DNA injected into Xenopus oocyte nuclei is transcribed by RNA polymerase B. SV40 DNA I. injected into Xenopus oocyte nuclei is transcribed. The SV40-specific RNA molecules migrate on sucrose gradients as do viral RNAs formed in infected green monkey cells but a variable proportion of RNA sequences complementary to SV40 DNA is also found in the light region of the gradients. All SV40-specific RNA species seem to be synthesized by RNA polymerase B as their synthesis is completely sensitive to low concentrations (0.1 microgram/ml) of alpha-amanitin. Concomittantly, the formation of SV40-specific proteins (tumor antigens) is inhibited by injecting alpha-amanitin together with the SV40 DNA."}
{"id": "PMID:222492", "title": "[Attempt at the evaluation of stromal reactions in orofacial tumors].", "content": "A group of 130 patients with malignant tumours of the orofacial region were examined. Each patient was investigated for tumour tissue stromal reaction in terms of topography, quantity and quality of the infiltrate, and with a view to the presence of necrosis. A comprehensive analysis found no direct correlation between stromal reaction and the patients' survival times.", "contents": "[Attempt at the evaluation of stromal reactions in orofacial tumors]. A group of 130 patients with malignant tumours of the orofacial region were examined. Each patient was investigated for tumour tissue stromal reaction in terms of topography, quantity and quality of the infiltrate, and with a view to the presence of necrosis. A comprehensive analysis found no direct correlation between stromal reaction and the patients' survival times."}
{"id": "PMID:222494", "title": "Comparative effects of ethanol, n-propranol and isopropanol on lipid disposal by rat liver.", "content": "Besides ethanol, other aliphatic alcohols such as n-propanol and isopropanol induce a triacylglycerol (TAG) accumulation in the liver. To determine whether a common mechanism is responsible for the effects of these three alcohols on hepatic lipid metabolism, each was administered by gastric tube to female Wistar rats at the dose of 50 mmol/kg body wt. Whichever alcohol was administered, the hepatic triacylglycerol accumulation was found to be related to the duration of elevated blood alcohol concentration. After administration of n-propanol or isopropanol, the liver [14C]palmitate uptake was increased whereas hepatic palmitate oxidation to 14CO2 was impaired and palmitate esterification into TAG enhanced; these perturbations were however more discrete than after ethanol administration. In contrast to ethanol and n-propanol which, at the dose presently used, increase precursor incorporation into blood TAG, isopropanol inhibits this incorporation. Interference with the process of very low density lipoprotein (VLDL) synthesis and/or secretion, which appears only at a late stage of isopropanol intoxication, is probably responsible for the intensity and duration of the fatty liver observed after administration of this alcohol.", "contents": "Comparative effects of ethanol, n-propranol and isopropanol on lipid disposal by rat liver. Besides ethanol, other aliphatic alcohols such as n-propanol and isopropanol induce a triacylglycerol (TAG) accumulation in the liver. To determine whether a common mechanism is responsible for the effects of these three alcohols on hepatic lipid metabolism, each was administered by gastric tube to female Wistar rats at the dose of 50 mmol/kg body wt. Whichever alcohol was administered, the hepatic triacylglycerol accumulation was found to be related to the duration of elevated blood alcohol concentration. After administration of n-propanol or isopropanol, the liver [14C]palmitate uptake was increased whereas hepatic palmitate oxidation to 14CO2 was impaired and palmitate esterification into TAG enhanced; these perturbations were however more discrete than after ethanol administration. In contrast to ethanol and n-propanol which, at the dose presently used, increase precursor incorporation into blood TAG, isopropanol inhibits this incorporation. Interference with the process of very low density lipoprotein (VLDL) synthesis and/or secretion, which appears only at a late stage of isopropanol intoxication, is probably responsible for the intensity and duration of the fatty liver observed after administration of this alcohol."}
{"id": "PMID:222496", "title": "ESR determinations of membrane permeability in a yeast sterol mutant.", "content": "Yeast sterol mutants were subjected to ESR analysis in an attempt to elucidate how altered sterol composition correlates with membrane permeability. The technique requires spin labeling the intact yeast cells with a small, water-soluble nitroxide probe (2,2,5,5 tetramethyl-3-pyrrolin-1-oxyl-3-carboxylic acid, PCA), suspending cells in a NiCl2 solution, and measuring the extent of Ni2+ entry through the membrane by its magnetic dipolar line broadening effect on the PCA signal. The wild type, A184D, was found to be impermeable to Ni2+ during all growth phases while the sterol mutant erg 6/2 was readily permeable to Ni2+. Other sources of line broadening such as increased rotational correlation time and cell nonviability are shown to be neglibible. Internal Ni2+ concentrations for erg 6/2 and kinetics of Ni2+ entry were determined.", "contents": "ESR determinations of membrane permeability in a yeast sterol mutant. Yeast sterol mutants were subjected to ESR analysis in an attempt to elucidate how altered sterol composition correlates with membrane permeability. The technique requires spin labeling the intact yeast cells with a small, water-soluble nitroxide probe (2,2,5,5 tetramethyl-3-pyrrolin-1-oxyl-3-carboxylic acid, PCA), suspending cells in a NiCl2 solution, and measuring the extent of Ni2+ entry through the membrane by its magnetic dipolar line broadening effect on the PCA signal. The wild type, A184D, was found to be impermeable to Ni2+ during all growth phases while the sterol mutant erg 6/2 was readily permeable to Ni2+. Other sources of line broadening such as increased rotational correlation time and cell nonviability are shown to be neglibible. Internal Ni2+ concentrations for erg 6/2 and kinetics of Ni2+ entry were determined."}
{"id": "PMID:222497", "title": "[Comparison of exogenous cell fusion induced by a wild and two mutant strains of sheep Visna virus].", "content": "Exogen cell fusion induced in vitro by a wild strain of Visna virus of Sheep is compared with two mutant strains isolated from the precedent. One of them produces large plaques in vitro (strain LPF), and the other produces small plaques (strain SPF). These strains behave in different ways according to infection multiplicity, type of cells, temperature and timing of fusing activity. Taking the wild strain K 796 as a base of reference, the strain SPF seems to have a higher rate fusing activity and the strain LPF lower rate of fusing activity.", "contents": "[Comparison of exogenous cell fusion induced by a wild and two mutant strains of sheep Visna virus]. Exogen cell fusion induced in vitro by a wild strain of Visna virus of Sheep is compared with two mutant strains isolated from the precedent. One of them produces large plaques in vitro (strain LPF), and the other produces small plaques (strain SPF). These strains behave in different ways according to infection multiplicity, type of cells, temperature and timing of fusing activity. Taking the wild strain K 796 as a base of reference, the strain SPF seems to have a higher rate fusing activity and the strain LPF lower rate of fusing activity."}
{"id": "PMID:222498", "title": "Atherogenesis: a postprandial phenomenon.", "content": "The hypothesis that plasma chylomicrons in persons who ingest a cholesterol-rich diet are atherogenic is evaluated. Evidence is presented that in humans, and experimental animals, chylomicron remnants as well as low-density lipoproteins are taken up by arterial cells. In persons who do not have familial hyperlipoproteinemia, atherogenesis may occur during the postprandial period. Research directions that may contribute to the evaluation of chylomicron remnants as a risk factor for atherogenesis are discussed. Lipoprotein studies after administration of a test meal containing fat and cholesterol are urgently needed.", "contents": "Atherogenesis: a postprandial phenomenon. The hypothesis that plasma chylomicrons in persons who ingest a cholesterol-rich diet are atherogenic is evaluated. Evidence is presented that in humans, and experimental animals, chylomicron remnants as well as low-density lipoproteins are taken up by arterial cells. In persons who do not have familial hyperlipoproteinemia, atherogenesis may occur during the postprandial period. Research directions that may contribute to the evaluation of chylomicron remnants as a risk factor for atherogenesis are discussed. Lipoprotein studies after administration of a test meal containing fat and cholesterol are urgently needed."}
{"id": "PMID:222499", "title": "Oral contraceptive use and fasting triglyceride, plasma cholesterol and HDL cholesterol.", "content": "Fasting plasma triglyceride, plasma cholesterol and high-density lipoprotein (HDL) cholesterol levels were studied for 190 white women, ages 21--39 years, who were classified according to their oral contraceptive (OC) usage patterns at two community surveys, 3 years apart. The mean level of fasting triglyceride was higher among current OC users (95 mg/100 ml) than among nonusers (73 mg/100 ml) (p = 0.002). After adjustment for the possible confounding effects of age, weight, current cigarette smoking and fasting glucose level, current OC users still had a mean plasma triglyceride level 19 mg/100 ml higher than that of nonusers (p = 0.007). Current OC users also appeared to have somewhat higher levels of total cholesterol which were of borderline significance in crude and adjusted analyses. There was a nonsignificant inverse relationship of OC use with HDL cholesterol levels. Past use did not affect these results, indicating that the OC-induced lipid changes were reversible.", "contents": "Oral contraceptive use and fasting triglyceride, plasma cholesterol and HDL cholesterol. Fasting plasma triglyceride, plasma cholesterol and high-density lipoprotein (HDL) cholesterol levels were studied for 190 white women, ages 21--39 years, who were classified according to their oral contraceptive (OC) usage patterns at two community surveys, 3 years apart. The mean level of fasting triglyceride was higher among current OC users (95 mg/100 ml) than among nonusers (73 mg/100 ml) (p = 0.002). After adjustment for the possible confounding effects of age, weight, current cigarette smoking and fasting glucose level, current OC users still had a mean plasma triglyceride level 19 mg/100 ml higher than that of nonusers (p = 0.007). Current OC users also appeared to have somewhat higher levels of total cholesterol which were of borderline significance in crude and adjusted analyses. There was a nonsignificant inverse relationship of OC use with HDL cholesterol levels. Past use did not affect these results, indicating that the OC-induced lipid changes were reversible."}
{"id": "PMID:222501", "title": "alpha-Amylase activity by the Beckman reaction system and suppression by pyruvate.", "content": "We evaluated the new Beckman Enzymatic Amyalse-DS Method with maltotetraose as substrate. Our findings indicate that the method is approximately twice as sensitive as the old method involving soluble starch [Clin. Chem. 24, 762 (1978)]. The new method also shows a linear rate of reaction, in contrast to the curvilinear rate previously observed with the old method. The Km with maltotetraose is 0.77 g/L, or about twice that with soluble starch (0.42 g/L). The method correlates well with the Phadebas alpha-amylase method (r = 0.974 and 0.991 on 84 serum and 52 urine specimens, respectively). Of 43 specimens with high concentrations of pyruvate we examined for interference with alpha-amylase activity, only six showed interference when maltotetraose was the substrate. (With both Beckman methods the reaction of pyruvate with NADH produced lactate and NAD+ in the presence of lactate dehydrogenase as contaminant.) Pyruvate interference decreased with increases in (a) the alpha-amylase activity of the specimen, (b) the amount of NADH initially present in the maltotetraose reagent, and (c) the length of time the reconstituted maltotetroase reagent was allowed to stand before being used.", "contents": "alpha-Amylase activity by the Beckman reaction system and suppression by pyruvate. We evaluated the new Beckman Enzymatic Amyalse-DS Method with maltotetraose as substrate. Our findings indicate that the method is approximately twice as sensitive as the old method involving soluble starch [Clin. Chem. 24, 762 (1978)]. The new method also shows a linear rate of reaction, in contrast to the curvilinear rate previously observed with the old method. The Km with maltotetraose is 0.77 g/L, or about twice that with soluble starch (0.42 g/L). The method correlates well with the Phadebas alpha-amylase method (r = 0.974 and 0.991 on 84 serum and 52 urine specimens, respectively). Of 43 specimens with high concentrations of pyruvate we examined for interference with alpha-amylase activity, only six showed interference when maltotetraose was the substrate. (With both Beckman methods the reaction of pyruvate with NADH produced lactate and NAD+ in the presence of lactate dehydrogenase as contaminant.) Pyruvate interference decreased with increases in (a) the alpha-amylase activity of the specimen, (b) the amount of NADH initially present in the maltotetraose reagent, and (c) the length of time the reconstituted maltotetroase reagent was allowed to stand before being used."}
{"id": "PMID:222502", "title": "A liquid chromatography-assisted assay for angiotensin-converting enzyme (peptidyl dipeptidase) in serum.", "content": "I describe modification of the spectrophotometric assay described by Cushman and Cheung [biochem. Pharmacol. 20, 1637 (1971)] for serum angiotensin-converting enzyme, with use of \"high-pressure\" liquid chromatography to measure the hippuric acid end product. After reaction of 10 microL of untreated serum with the angiotensin-converting enzyme substrate analog hippuryl-L-histidyl-L-leucine, the hippuric acid produced is extracted into ethyl acetate and quantitated, relative to an added internal standard, by liquid chromatography. Total chromatographic running time is 3 min per sample, with a within-run CV of 4.3% and a day-to-day CV of 6.6%, for aliquots of plasma supplemented with 1 mmol of hippuric acid per liter. The measurements are linear for hippuric acid in amounts up to 20 nmol per assay. The presence of large quantities of lipid in the serum did not affect the accuracy of the determination.", "contents": "A liquid chromatography-assisted assay for angiotensin-converting enzyme (peptidyl dipeptidase) in serum. I describe modification of the spectrophotometric assay described by Cushman and Cheung [biochem. Pharmacol. 20, 1637 (1971)] for serum angiotensin-converting enzyme, with use of \"high-pressure\" liquid chromatography to measure the hippuric acid end product. After reaction of 10 microL of untreated serum with the angiotensin-converting enzyme substrate analog hippuryl-L-histidyl-L-leucine, the hippuric acid produced is extracted into ethyl acetate and quantitated, relative to an added internal standard, by liquid chromatography. Total chromatographic running time is 3 min per sample, with a within-run CV of 4.3% and a day-to-day CV of 6.6%, for aliquots of plasma supplemented with 1 mmol of hippuric acid per liter. The measurements are linear for hippuric acid in amounts up to 20 nmol per assay. The presence of large quantities of lipid in the serum did not affect the accuracy of the determination."}
{"id": "PMID:222503", "title": "Human corticotropin (ACTH) radioimmunoassay with synthetic 1--24 ACTH.", "content": "A corticotropin antiserum was obtained from rabbits immunized with synthetic 1--24 corticotropin conjugated with bovine serum albumin. The antiserum did not cross react with synthetic alpha-melanotropin or with synthetic beta-endorphin and had a cross reactivity of 0.23% with human beta-lipotropin. We developed a radioimmunoassay with the antiserum obtained, in which we used polyethylene glycol in conjunction with a second precipitating antibody for fast (15-min) separation of antibody-bound and free corticotropin. The assay had a sensitivity of 16 ng/L and was validated on patients with various pituitary and adrenal diseases. From 103 normal subjects, the median value for corticotropin in specimens collected during the morning was 34 ng/L of plasma; the upper 95% confidence limit of the normal range was 98 ng/L.", "contents": "Human corticotropin (ACTH) radioimmunoassay with synthetic 1--24 ACTH. A corticotropin antiserum was obtained from rabbits immunized with synthetic 1--24 corticotropin conjugated with bovine serum albumin. The antiserum did not cross react with synthetic alpha-melanotropin or with synthetic beta-endorphin and had a cross reactivity of 0.23% with human beta-lipotropin. We developed a radioimmunoassay with the antiserum obtained, in which we used polyethylene glycol in conjunction with a second precipitating antibody for fast (15-min) separation of antibody-bound and free corticotropin. The assay had a sensitivity of 16 ng/L and was validated on patients with various pituitary and adrenal diseases. From 103 normal subjects, the median value for corticotropin in specimens collected during the morning was 34 ng/L of plasma; the upper 95% confidence limit of the normal range was 98 ng/L."}
{"id": "PMID:222504", "title": "Evaluation of commercial heparin preparations for use in the heparin-Mn2+ method for measuring cholesterol in high-sensity lipoprotein.", "content": "Commercial heparin preparations (18 lots) from seven manufacturers were compared in the heparin-Mn2+ procedure for high-density-lipoprotein cholesterol quantitation. With normotriglyceridemic samples, 16 heparin lots, isolated from porcine intestinal mucosa, gave mean values for supernatant cholesterol that did not differ statistically; all were within 7 mg/L. Two heparin preparations from bovine lung gave results that were slightly (16 mg/L, average) but significantly (p less than 0.005) lower. With hypertriglyceridemic samples, we observed greater variation in supernatant cholesterol among the heparin preparations, which was ascribable to variable sedimentation by centrifugation of very-low-density and low-density lipoproteins precipitated by heparin-Mn2+ treatment. If the precipitated lipoproteins were completely removed by an ultrafiltration procedure, we saw no significant difference among the heparin preparations for results with hypertriglyceridemic samples.", "contents": "Evaluation of commercial heparin preparations for use in the heparin-Mn2+ method for measuring cholesterol in high-sensity lipoprotein. Commercial heparin preparations (18 lots) from seven manufacturers were compared in the heparin-Mn2+ procedure for high-density-lipoprotein cholesterol quantitation. With normotriglyceridemic samples, 16 heparin lots, isolated from porcine intestinal mucosa, gave mean values for supernatant cholesterol that did not differ statistically; all were within 7 mg/L. Two heparin preparations from bovine lung gave results that were slightly (16 mg/L, average) but significantly (p less than 0.005) lower. With hypertriglyceridemic samples, we observed greater variation in supernatant cholesterol among the heparin preparations, which was ascribable to variable sedimentation by centrifugation of very-low-density and low-density lipoproteins precipitated by heparin-Mn2+ treatment. If the precipitated lipoproteins were completely removed by an ultrafiltration procedure, we saw no significant difference among the heparin preparations for results with hypertriglyceridemic samples."}
{"id": "PMID:222505", "title": "Radioimmunoassay of total urinary estrogens.", "content": "We describe a radioimmunoassay for total estrogens in urine. Estrogens are extracted by adsorption on XAD-2 resin, eluted with methanol, and acid-hydrolyzed. Estrogens are then determined in a diluted aliquot of the hydrolysate. Within-run coefficients of variation for estriol values between 6.0 and 100 micrograms/L were less than 5%; between-run CV was 19.6% at an estriol concentration of 16.8 microgram/L. A correlation coefficient of 0.96 was found on comparison of the radioimmunoassay (y) with a standard fluorometric assay (x); the regression equation is y = 2.18 x - 6.70 micrograms/L. Determination on pregnancy and non-pregnancy urine can be done within 4 h.", "contents": "Radioimmunoassay of total urinary estrogens. We describe a radioimmunoassay for total estrogens in urine. Estrogens are extracted by adsorption on XAD-2 resin, eluted with methanol, and acid-hydrolyzed. Estrogens are then determined in a diluted aliquot of the hydrolysate. Within-run coefficients of variation for estriol values between 6.0 and 100 micrograms/L were less than 5%; between-run CV was 19.6% at an estriol concentration of 16.8 microgram/L. A correlation coefficient of 0.96 was found on comparison of the radioimmunoassay (y) with a standard fluorometric assay (x); the regression equation is y = 2.18 x - 6.70 micrograms/L. Determination on pregnancy and non-pregnancy urine can be done within 4 h."}
{"id": "PMID:222508", "title": "Four electrophoretic methods compared for diagnosis of type III hyperlipoproteinemia.", "content": "Blood drawn from 192 probands and 1129 first-degree relatives who were participants in a collaborative family study of hyperlipoproteinemia at nine Lipid Research Clinics was used to prepare aliquots of whole plasma and top (d less than 1.006 g/mL) and bottom (d greater than 1.006 g/mL) ultracentrifugal fractions. Each aliquot was analyzed at a central laboratory by electrophoresis on paper, agarose, and polyacrylamide gel, and by a combined electrophoretic precipitation technique. The electrophoretograms were evaluated for the presence or absence of a \"floating-beta\" lipoprotein band. All four methods agreed completely for 92.3% of the samples. An additional 2.0% of the samples were in agreement for three electrophoretic methods, but the paper electrophoretic results were not interpretable. Another 1.9% were considered to be \"floating-beta\" positive by paper electrophoresis but negative by the other three electrophoretic methods.", "contents": "Four electrophoretic methods compared for diagnosis of type III hyperlipoproteinemia. Blood drawn from 192 probands and 1129 first-degree relatives who were participants in a collaborative family study of hyperlipoproteinemia at nine Lipid Research Clinics was used to prepare aliquots of whole plasma and top (d less than 1.006 g/mL) and bottom (d greater than 1.006 g/mL) ultracentrifugal fractions. Each aliquot was analyzed at a central laboratory by electrophoresis on paper, agarose, and polyacrylamide gel, and by a combined electrophoretic precipitation technique. The electrophoretograms were evaluated for the presence or absence of a \"floating-beta\" lipoprotein band. All four methods agreed completely for 92.3% of the samples. An additional 2.0% of the samples were in agreement for three electrophoretic methods, but the paper electrophoretic results were not interpretable. Another 1.9% were considered to be \"floating-beta\" positive by paper electrophoresis but negative by the other three electrophoretic methods."}
{"id": "PMID:222509", "title": "Improved method for simultaneous determination of cholesterol in high- and low-density lipoproteins.", "content": "A previously described procedure for simultaneous determination of cholesterol in high- and low-density lipoproteins (HDL and LDL) [Clin. Chem. 24, 1504--1508 (1978)] has been improved by using centrifugation instead of ultrafiltration. Addition of NICl2 (2.0 mmol/L) to the reagent produced a good separation of HDL from the complex of low- and very-low-density lipoprotein-heparin-Ca2+ on centrifugation at 3000 rpm for 15 min. Replicate analyses for high-density lipoprotein cholesterol by the present method demonstrated the following intra-assay precision: mean = 389 mg/L, SD = 11 mg/L, CV = 2.8%. The present (y) and original (x) methods gave results that agreed reasonably well (n = 50, r = 0.960, y = 1.0x + 0.9). The enzymic method for HDL- or (HDL + LDL)-cholesterol after the separation of their fractions gave erroneous results, in particular in the cases of hyperbilirubinemic sera and in (HDL + LDL) fractions.", "contents": "Improved method for simultaneous determination of cholesterol in high- and low-density lipoproteins. A previously described procedure for simultaneous determination of cholesterol in high- and low-density lipoproteins (HDL and LDL) [Clin. Chem. 24, 1504--1508 (1978)] has been improved by using centrifugation instead of ultrafiltration. Addition of NICl2 (2.0 mmol/L) to the reagent produced a good separation of HDL from the complex of low- and very-low-density lipoprotein-heparin-Ca2+ on centrifugation at 3000 rpm for 15 min. Replicate analyses for high-density lipoprotein cholesterol by the present method demonstrated the following intra-assay precision: mean = 389 mg/L, SD = 11 mg/L, CV = 2.8%. The present (y) and original (x) methods gave results that agreed reasonably well (n = 50, r = 0.960, y = 1.0x + 0.9). The enzymic method for HDL- or (HDL + LDL)-cholesterol after the separation of their fractions gave erroneous results, in particular in the cases of hyperbilirubinemic sera and in (HDL + LDL) fractions."}
{"id": "PMID:222511", "title": "Triglyceride-poor very low density lipoprotein in human serum.", "content": "The chemical and physical properties of very low density lipoproteins, isolated from the pool of the sera of 60 persons with high pre-beta and normal triglyceride and cholesterol concentrations, have been studied. These very low density lipoproteins, a designated as triglyceride-poor very low density lipoproteins, consist of 20.5% phospholipids, 30.8% free cholesterol, 15% cholesterol esters and 33.7% triglycerides. Their protein content consists of 54.5% apo B, 26% apo A, 11.5% apo E and only 8% apo C, so they differ from any serum lipoprotein described until now. Triglyceride-poor very low density lipoproteins consist of spherical particles 300-450 A in diameter as revealed by electron microscopy.", "contents": "Triglyceride-poor very low density lipoprotein in human serum. The chemical and physical properties of very low density lipoproteins, isolated from the pool of the sera of 60 persons with high pre-beta and normal triglyceride and cholesterol concentrations, have been studied. These very low density lipoproteins, a designated as triglyceride-poor very low density lipoproteins, consist of 20.5% phospholipids, 30.8% free cholesterol, 15% cholesterol esters and 33.7% triglycerides. Their protein content consists of 54.5% apo B, 26% apo A, 11.5% apo E and only 8% apo C, so they differ from any serum lipoprotein described until now. Triglyceride-poor very low density lipoproteins consist of spherical particles 300-450 A in diameter as revealed by electron microscopy."}
{"id": "PMID:222512", "title": "Urinary high density lipoprotein in minimal change glomerular disease and chronic glomerulopathies.", "content": "Serum lipids and lipoproteins and urinary apolipoprotein A (Apo A) were determined in two groups of patients. One group consisted of 11 children (ages ranging from 4 to 14 years) with minimal change glomerular disease. The other group consisted of 13 patients, eight less than 19 years old five adults, with different types of chronic glomerulopathy. Elimination of urinary lysozyme was a feature of chronic glomerulopathies, and creatinine clearances were also significantly lower in this group. Patients with chronic glomerulopathies had significantly lower HDL cholesterol and Apo A concentrations in their sera. In contrast, urinary Apo A concentrations were significantly higher in patients with chronic glomerulopathies, who also showed significantly lower urinary protein selectivities. Lipoprotein electrophoresis of urines containing Apo A showed distinct high-density lipoprotein (HDL) fractions, suggesting that HDL is eliminated in the urine as a result of increased glomerular permeability. This is also supported by a correlation coefficient of 0.77 between the selectivity indices and the ratio of urinary Apo A to total proteinuria. The determination of urinary Apo A appears to give valuable diagnostic information in patients with glomerular disease. According to our results the absence of urinary Apo A is very suggestive of minimal change glomerular disease.", "contents": "Urinary high density lipoprotein in minimal change glomerular disease and chronic glomerulopathies. Serum lipids and lipoproteins and urinary apolipoprotein A (Apo A) were determined in two groups of patients. One group consisted of 11 children (ages ranging from 4 to 14 years) with minimal change glomerular disease. The other group consisted of 13 patients, eight less than 19 years old five adults, with different types of chronic glomerulopathy. Elimination of urinary lysozyme was a feature of chronic glomerulopathies, and creatinine clearances were also significantly lower in this group. Patients with chronic glomerulopathies had significantly lower HDL cholesterol and Apo A concentrations in their sera. In contrast, urinary Apo A concentrations were significantly higher in patients with chronic glomerulopathies, who also showed significantly lower urinary protein selectivities. Lipoprotein electrophoresis of urines containing Apo A showed distinct high-density lipoprotein (HDL) fractions, suggesting that HDL is eliminated in the urine as a result of increased glomerular permeability. This is also supported by a correlation coefficient of 0.77 between the selectivity indices and the ratio of urinary Apo A to total proteinuria. The determination of urinary Apo A appears to give valuable diagnostic information in patients with glomerular disease. According to our results the absence of urinary Apo A is very suggestive of minimal change glomerular disease."}
{"id": "PMID:222513", "title": "The lipoprotein composition of amniotic fluid.", "content": "The lipoprotein composition of amniotic fluid (AF) has been studied and it was found that it consists of high density lipoprotein (HDL) only. At about the 26th week of pregnancy the HDL content reaches a maximum and decreases thereafter. On crossed immunoelectrophoresis the HDL of AF was separated into two components if the agar layer contained an antiserum against apolipoprotein A-I. The component with the higher electrophoretic mobility (but not the slower moving component) could also be visualized with an antiserum against HDL. When maternal or umbilical cord serum (UCS) was analysed by crossed immunoelectrophoresis using the anti-apoA-I antiserum, we found that they only contained the faster moving lipoprotein component. If UCS was treated with phospholipase A2 and then subjected to crossed immunoelectrophoresis, the slower moving component appeared at the expense of the faster one. Likewise when UCS was incubated with AF from the 15th week of pregnancy or later, the lipoprotein component of UCS with the high mobility was partially converted to the component with the slower mobility. It is concluded that AF probably contains a phospholipase, an enzyme which may promote the onset of labour.", "contents": "The lipoprotein composition of amniotic fluid. The lipoprotein composition of amniotic fluid (AF) has been studied and it was found that it consists of high density lipoprotein (HDL) only. At about the 26th week of pregnancy the HDL content reaches a maximum and decreases thereafter. On crossed immunoelectrophoresis the HDL of AF was separated into two components if the agar layer contained an antiserum against apolipoprotein A-I. The component with the higher electrophoretic mobility (but not the slower moving component) could also be visualized with an antiserum against HDL. When maternal or umbilical cord serum (UCS) was analysed by crossed immunoelectrophoresis using the anti-apoA-I antiserum, we found that they only contained the faster moving lipoprotein component. If UCS was treated with phospholipase A2 and then subjected to crossed immunoelectrophoresis, the slower moving component appeared at the expense of the faster one. Likewise when UCS was incubated with AF from the 15th week of pregnancy or later, the lipoprotein component of UCS with the high mobility was partially converted to the component with the slower mobility. It is concluded that AF probably contains a phospholipase, an enzyme which may promote the onset of labour."}
{"id": "PMID:222514", "title": "The effect of fasting on the interactions between human low density lipoproteins and calcium, heparin and chondroitin sulfate.", "content": "Fasting modified the in vitro interactions between low density lipoproteins (LDL) and glycosaminoglycans. Calcium had a potentiating effect on these interactions. LDL-calcium-heparin interaction was dependent on the presence of sialic acid whereas LDL-calcium-chondroitin sulfate interaction was inversely correlated with cholesterol content.", "contents": "The effect of fasting on the interactions between human low density lipoproteins and calcium, heparin and chondroitin sulfate. Fasting modified the in vitro interactions between low density lipoproteins (LDL) and glycosaminoglycans. Calcium had a potentiating effect on these interactions. LDL-calcium-heparin interaction was dependent on the presence of sialic acid whereas LDL-calcium-chondroitin sulfate interaction was inversely correlated with cholesterol content."}
{"id": "PMID:222518", "title": "Polymorphonuclear leucocyte fluorescence and cryoglobulin phagocytosis in systemic lupus erythematosus.", "content": "Peripheral blood polymorphonuclear leucocytes (PMN) and cryoglobulins were isolated from patients with systemic lupus erythematosus (SLE). Fluorescent inclusions were found in PMN. Normal donor PMN were incubated with the sera and cryoglobulins from SLE patients. In most cases inclusions were observed after incubation. The high incidence of anti-IgG activity in phagocytosed cryoglobulins confirms the importance of the rheumatoid factor in phagocytosis of immune complexes. It is concluded that phagocytosis of cryoglobulins supports the suggestion that cryoglobulins are a subpopulation of immune complexes.", "contents": "Polymorphonuclear leucocyte fluorescence and cryoglobulin phagocytosis in systemic lupus erythematosus. Peripheral blood polymorphonuclear leucocytes (PMN) and cryoglobulins were isolated from patients with systemic lupus erythematosus (SLE). Fluorescent inclusions were found in PMN. Normal donor PMN were incubated with the sera and cryoglobulins from SLE patients. In most cases inclusions were observed after incubation. The high incidence of anti-IgG activity in phagocytosed cryoglobulins confirms the importance of the rheumatoid factor in phagocytosis of immune complexes. It is concluded that phagocytosis of cryoglobulins supports the suggestion that cryoglobulins are a subpopulation of immune complexes."}
{"id": "PMID:222519", "title": "Induction of plaque-forming cells in human blood lymphocytes cultured in the presence of antigen and Epstein-Barr virus: a study with normal donors and infectious mononucleosis patients.", "content": "Normal human peripheral blood lymphocytes, stimulated in vitro with SRBC in the presence of Epstein-Barr virus (EBV), gave rise to plaque-forming cells (PFC) specific for the antigen. PFC levels were very low before day 4 and increased thereafter, reaching a maximum around day 8. However, the kinetics of the response varied considerably from donor to donor and from experiment to experiment. In some instances a second peak of PFC was obtained beyond day 10. Large differences in the magnitude of the response were observed among different normal donors, the overall responsiveness range covering four orders of magnitude. Peripheral blood lymphocytes from infectious mononucleosis patients in the acute stage of the disease, when a high titre of heterophil and anti-EBV antibodies were present, did not give rise to PFC. A return to normal responses was observed during recovery from the disease.", "contents": "Induction of plaque-forming cells in human blood lymphocytes cultured in the presence of antigen and Epstein-Barr virus: a study with normal donors and infectious mononucleosis patients. Normal human peripheral blood lymphocytes, stimulated in vitro with SRBC in the presence of Epstein-Barr virus (EBV), gave rise to plaque-forming cells (PFC) specific for the antigen. PFC levels were very low before day 4 and increased thereafter, reaching a maximum around day 8. However, the kinetics of the response varied considerably from donor to donor and from experiment to experiment. In some instances a second peak of PFC was obtained beyond day 10. Large differences in the magnitude of the response were observed among different normal donors, the overall responsiveness range covering four orders of magnitude. Peripheral blood lymphocytes from infectious mononucleosis patients in the acute stage of the disease, when a high titre of heterophil and anti-EBV antibodies were present, did not give rise to PFC. A return to normal responses was observed during recovery from the disease."}
{"id": "PMID:222527", "title": "Opsomyoclonus and neuroblastoma. Response to ACTH.", "content": "Children with neuroblastoma whose opsomyoclonus recurs or persists after initial surgery should be carefully evaluated for tumor. If no tumor is detectable, therapy with ACTH should be considered in patients whose symptomatology is severe enough to compromise normal development.", "contents": "Opsomyoclonus and neuroblastoma. Response to ACTH. Children with neuroblastoma whose opsomyoclonus recurs or persists after initial surgery should be carefully evaluated for tumor. If no tumor is detectable, therapy with ACTH should be considered in patients whose symptomatology is severe enough to compromise normal development."}
{"id": "PMID:222528", "title": "Ovarian tumours in children--a review of 40 cases.", "content": "The records of 40 children treated for ovarian tumours in Manchester since 1940 are reviewed. The series includes 12 dysgerminomas, nine endodermal sinus tumours, six malignant teratomas, three granulosa theca cell tumours, one Sertoli-Leydig cell tumour, one mixed chorioncarcinoma/dysgerminoma and eight cases of non-germ cell or uncertain origin. Presenting features and treatment are discussed. Survival is generally poor apart from the dysgerminomas, granulosa theca and Sertoli-Leydig cell tumours, all but one of whom are alive and disease free. The need for routine post-operative radiotherapy in cases in dysgerminoma confined to one ovary following total resection is questioned. Combination chemotherapy may improve survival in the future, particularly of children with endodermal sinus tumour. The only surviving child other than those mentioned above has had combination chemotherapy for an endodermal sinus tumour.", "contents": "Ovarian tumours in children--a review of 40 cases. The records of 40 children treated for ovarian tumours in Manchester since 1940 are reviewed. The series includes 12 dysgerminomas, nine endodermal sinus tumours, six malignant teratomas, three granulosa theca cell tumours, one Sertoli-Leydig cell tumour, one mixed chorioncarcinoma/dysgerminoma and eight cases of non-germ cell or uncertain origin. Presenting features and treatment are discussed. Survival is generally poor apart from the dysgerminomas, granulosa theca and Sertoli-Leydig cell tumours, all but one of whom are alive and disease free. The need for routine post-operative radiotherapy in cases in dysgerminoma confined to one ovary following total resection is questioned. Combination chemotherapy may improve survival in the future, particularly of children with endodermal sinus tumour. The only surviving child other than those mentioned above has had combination chemotherapy for an endodermal sinus tumour."}
{"id": "PMID:222525", "title": "Newer knowledge of vitamin D and its metabolites in health and disease.", "content": "Renewed interest in vitamin D, over the past several years, has resulted in increased knowledge of (1) the metabolic pathways which result in production of an active metabolite, (2) the role of its various metabolities at target tissues, and (3) its interaction with other control systems in the maintenance of calcium/phosphorus homeostasis. Presently, a role for 1, 25-(OH)2 D3 can be identified in the regulation of (1) calcium and phosphorus absorption from the intestine, (2) PTH production, and (3) calcium mobilization from bone (in conjunction with PTH). Several other actions at the kidney, muscle and other organs have been suggested but not proven. In contrast, the actual process of bone mineralization may be dependent, in part, on 25-(OH) D3. Despite these major advances in our knowledge, many gaps remain and controversial data continues unresolved. However, application of this new information to analysis of a wide variety of disease states has resulted in remarkable progress in appreciation of the pathogenesis and appropriate treatment for these diseases. Nonetheless, continued research promises further advances and more precise definition of disease states as well as delineation of the therapeutic role of Vitamin D metabolites in their treatment.", "contents": "Newer knowledge of vitamin D and its metabolites in health and disease. Renewed interest in vitamin D, over the past several years, has resulted in increased knowledge of (1) the metabolic pathways which result in production of an active metabolite, (2) the role of its various metabolities at target tissues, and (3) its interaction with other control systems in the maintenance of calcium/phosphorus homeostasis. Presently, a role for 1, 25-(OH)2 D3 can be identified in the regulation of (1) calcium and phosphorus absorption from the intestine, (2) PTH production, and (3) calcium mobilization from bone (in conjunction with PTH). Several other actions at the kidney, muscle and other organs have been suggested but not proven. In contrast, the actual process of bone mineralization may be dependent, in part, on 25-(OH) D3. Despite these major advances in our knowledge, many gaps remain and controversial data continues unresolved. However, application of this new information to analysis of a wide variety of disease states has resulted in remarkable progress in appreciation of the pathogenesis and appropriate treatment for these diseases. Nonetheless, continued research promises further advances and more precise definition of disease states as well as delineation of the therapeutic role of Vitamin D metabolites in their treatment."}
{"id": "PMID:222526", "title": "Clostridium perfringens septic arthritis. Report of a case and review of the literature.", "content": "This is a report of Clostridium perfringens septic arthritis in a 5-year-old boy and a review of the literature on 6 previously reported cases. The treatment is the same as for other organisms producing septic arthritis.", "contents": "Clostridium perfringens septic arthritis. Report of a case and review of the literature. This is a report of Clostridium perfringens septic arthritis in a 5-year-old boy and a review of the literature on 6 previously reported cases. The treatment is the same as for other organisms producing septic arthritis."}
{"id": "PMID:222534", "title": "Some effects of short-term methylprednisolone therapy in normal cats.", "content": "Four normal cats were treated weekly for 4 weeks with repositol methylprednisolone. Hemograms, serum chemistry panels, urinalyses, 24 hour water consumption, physical and constitutional parameters, and blood cortisol responses to ACTH stimulation were monitored before and during a day were done prior to steroid therapy on each cat. Clinicopathologic abnormalities induced by steroid therapy were, on the whole, inconsistent and minor. The most important findings were: (1) marked steroid-induced suppression of blood cortisol responses to ACTH, and (2) a circadian rhythm of blood cortisol production that was opposite to that of humans and dogs.", "contents": "Some effects of short-term methylprednisolone therapy in normal cats. Four normal cats were treated weekly for 4 weeks with repositol methylprednisolone. Hemograms, serum chemistry panels, urinalyses, 24 hour water consumption, physical and constitutional parameters, and blood cortisol responses to ACTH stimulation were monitored before and during a day were done prior to steroid therapy on each cat. Clinicopathologic abnormalities induced by steroid therapy were, on the whole, inconsistent and minor. The most important findings were: (1) marked steroid-induced suppression of blood cortisol responses to ACTH, and (2) a circadian rhythm of blood cortisol production that was opposite to that of humans and dogs."}
{"id": "PMID:222535", "title": "Bovine abortion associated with mixed Movar 33/63 type herpesvirus and bovine viral diarrhea virus infection.", "content": "A herpesvirus and cytopathogenic bovine viral diarrhea virus were isolated from a bovine fetus aborted in the 6th month of gestation. The herpesvirus was serologically indistinguishable from bovine herpesviruses DN-599 and Movar 33/63.", "contents": "Bovine abortion associated with mixed Movar 33/63 type herpesvirus and bovine viral diarrhea virus infection. A herpesvirus and cytopathogenic bovine viral diarrhea virus were isolated from a bovine fetus aborted in the 6th month of gestation. The herpesvirus was serologically indistinguishable from bovine herpesviruses DN-599 and Movar 33/63."}
{"id": "PMID:222537", "title": "Cytochemistry of esterases.", "content": "Esterases are enzymes that cleave aliphatic and aromatic ester bonds. With the use of synthetic substrates, esterases can be demonstrated in hematopoietic cells. Using alpha naphthyl acetate or alpha naphthyl butyrate, nonspecific esterase activity can be demonstrated. Intense activity of nonspecific esterase that is inhibited by fluoride is characteristic of cells of monocytic or reticulum cell origin. Using naphthol ASD-chloroacetate, specific esterase activity can be detected. Specific esterase is a lysosomal enzyme and is a useful marker for cells of granulocytic origin. Distinctive patterns of specific and nonspecific esterase activities are found in marrow cells from patients with various types of hematologic disorders. With the use of electrophoretic techniques, isoenzymatic analysis of esterases can be achieved.", "contents": "Cytochemistry of esterases. Esterases are enzymes that cleave aliphatic and aromatic ester bonds. With the use of synthetic substrates, esterases can be demonstrated in hematopoietic cells. Using alpha naphthyl acetate or alpha naphthyl butyrate, nonspecific esterase activity can be demonstrated. Intense activity of nonspecific esterase that is inhibited by fluoride is characteristic of cells of monocytic or reticulum cell origin. Using naphthol ASD-chloroacetate, specific esterase activity can be detected. Specific esterase is a lysosomal enzyme and is a useful marker for cells of granulocytic origin. Distinctive patterns of specific and nonspecific esterase activities are found in marrow cells from patients with various types of hematologic disorders. With the use of electrophoretic techniques, isoenzymatic analysis of esterases can be achieved."}
{"id": "PMID:222538", "title": "Relative importance of alpha and beta adrenergic receptors during resuscitation.", "content": "Successful resuscitation from cardiac arrest in the asphyxiated dog model has been ascribed to the use of artificial ventilation, closed chest cardiac massage, and administration of a vasopressor. Controversy remains over whether the most commonly employed vasopressor, epinephrine, exerts its effects primarily by elevating diastolic pressure and reestablishing coronary flow, or by exciting cardiac pacemaker cells and enhancing myocardial contractility. To observe pure alpha and beta adrenergic receptor influences during resuscitation, three groups (alpha-blocked, beta-blocked, unblocked) of dogs were studied. beta-blocked dogs resuscitated with phenylephrine and unblocked dogs resuscitated with epinephrine experienced 100% successful resumption of spontaneous circulation after 5 min of asphyxia-induced arrest. Only 27% of alpha-blocked animals resuscitated with isoproterenol were successfully revived. The appearance of the ECG during cardiac arrest and resuscitation could in no way be used to predict the outcome of resuscitation attempts. Results suggest that, initially, alpha receptor stimulation with concomitant diastolic pressure elevation is more important to the success of resuscitation than beta receptor stimulation.", "contents": "Relative importance of alpha and beta adrenergic receptors during resuscitation. Successful resuscitation from cardiac arrest in the asphyxiated dog model has been ascribed to the use of artificial ventilation, closed chest cardiac massage, and administration of a vasopressor. Controversy remains over whether the most commonly employed vasopressor, epinephrine, exerts its effects primarily by elevating diastolic pressure and reestablishing coronary flow, or by exciting cardiac pacemaker cells and enhancing myocardial contractility. To observe pure alpha and beta adrenergic receptor influences during resuscitation, three groups (alpha-blocked, beta-blocked, unblocked) of dogs were studied. beta-blocked dogs resuscitated with phenylephrine and unblocked dogs resuscitated with epinephrine experienced 100% successful resumption of spontaneous circulation after 5 min of asphyxia-induced arrest. Only 27% of alpha-blocked animals resuscitated with isoproterenol were successfully revived. The appearance of the ECG during cardiac arrest and resuscitation could in no way be used to predict the outcome of resuscitation attempts. Results suggest that, initially, alpha receptor stimulation with concomitant diastolic pressure elevation is more important to the success of resuscitation than beta receptor stimulation."}
{"id": "PMID:222539", "title": "Influence of hydrochlorothiazide on the plasma levels of triglycerides, total cholesterol and HDL-cholesterol in patients with essential hypertension.", "content": "The influence of hydrochlorothiazide (HCT) treatment on the plasma levels of triglycerides, total cholesterol and high density lipoprotein cholesterol (HDL-cholesterol) was studied in 10 patients with essential hypertension. After a placebo period of 4 weeks, 50 mg HCT twice daily was given for a period of 9 months, followed by a second placebo period of 4 weeks. Triglycerides, total cholesterol and HDL-cholesterol were determined at the end of both placebo periods and after 1, 3, 6 and 9 months of HCT. For the whole group, there were no significant changes in triglycerides or HDL-cholesterol, whereas total cholesterol significantly increased during HCT. In 6 patients, plasma triglycerides were higher during HCT as compared to both placebo periods. In only 4 patients did HDL-cholesterol increase during HCT. Changes in triglycerides, total cholesterol and HDL-cholesterol were not related and no correlation was found with changes in blood pressure, body weight or serum potassium. In conclusion, this study confirms a possible adverse effect of diuretic treatment on plasma lipids, which should be considered when determining therapeutic regimens for hypertension.", "contents": "Influence of hydrochlorothiazide on the plasma levels of triglycerides, total cholesterol and HDL-cholesterol in patients with essential hypertension. The influence of hydrochlorothiazide (HCT) treatment on the plasma levels of triglycerides, total cholesterol and high density lipoprotein cholesterol (HDL-cholesterol) was studied in 10 patients with essential hypertension. After a placebo period of 4 weeks, 50 mg HCT twice daily was given for a period of 9 months, followed by a second placebo period of 4 weeks. Triglycerides, total cholesterol and HDL-cholesterol were determined at the end of both placebo periods and after 1, 3, 6 and 9 months of HCT. For the whole group, there were no significant changes in triglycerides or HDL-cholesterol, whereas total cholesterol significantly increased during HCT. In 6 patients, plasma triglycerides were higher during HCT as compared to both placebo periods. In only 4 patients did HDL-cholesterol increase during HCT. Changes in triglycerides, total cholesterol and HDL-cholesterol were not related and no correlation was found with changes in blood pressure, body weight or serum potassium. In conclusion, this study confirms a possible adverse effect of diuretic treatment on plasma lipids, which should be considered when determining therapeutic regimens for hypertension."}
{"id": "PMID:222552", "title": "[Autotransplantation of pancreas fragments in dogs with total pancreatectomy without separation of exo and endocrine tissue].", "content": "By total pancreatectomy 41 dogs were made diabetic. Of these, 15 dogs remained untreated, served as diabetic controls, and died within x = 7 +/- 1 days postoperatively. In the experimental groups the best results were obtained (as judged by K values of iv glucose tolerance test and iv Tolbutamide test curves) after 20 min of incubation with collagenase and immediate transplantation into the splenic pulp. After 15 min and 25 min of incubation, normoglycemia regularly occurred, but in the 20 min collagenase group the K values resembled most closely those of normal dogs. The animals stayed normoglycemic and were observed for up to 6 months. Splenectomy led to reocurrence of the diabetic state and death within 4.8 +/- 1.5 (S.E.) days.", "contents": "[Autotransplantation of pancreas fragments in dogs with total pancreatectomy without separation of exo and endocrine tissue]. By total pancreatectomy 41 dogs were made diabetic. Of these, 15 dogs remained untreated, served as diabetic controls, and died within x = 7 +/- 1 days postoperatively. In the experimental groups the best results were obtained (as judged by K values of iv glucose tolerance test and iv Tolbutamide test curves) after 20 min of incubation with collagenase and immediate transplantation into the splenic pulp. After 15 min and 25 min of incubation, normoglycemia regularly occurred, but in the 20 min collagenase group the K values resembled most closely those of normal dogs. The animals stayed normoglycemic and were observed for up to 6 months. Splenectomy led to reocurrence of the diabetic state and death within 4.8 +/- 1.5 (S.E.) days."}
{"id": "PMID:222553", "title": "[Experimental studies of enzyme activity in the large intestine].", "content": "1. A kallikrein is isolated from the human colon. 2. A collagenolytic enzyme is detectable in this tissue. 3. On day 3 after surgery on the colon of the rat, an enhanced collagenolytic activity is demonstrated.", "contents": "[Experimental studies of enzyme activity in the large intestine]. 1. A kallikrein is isolated from the human colon. 2. A collagenolytic enzyme is detectable in this tissue. 3. On day 3 after surgery on the colon of the rat, an enhanced collagenolytic activity is demonstrated."}
{"id": "PMID:222554", "title": "[Methylprednisolone-induced inhibition of the sympathetic vasomotor tonus in hemorrhagic shock].", "content": "In anesthetized cats massive doses of methylprednisolon (40 mg/kg body wt.) induce a blood pressure decrease with bradycardia, which is not transmitted through vagal efferents. These effects are due to an inhibition of sympathetic outflow to heart and vessels.", "contents": "[Methylprednisolone-induced inhibition of the sympathetic vasomotor tonus in hemorrhagic shock]. In anesthetized cats massive doses of methylprednisolon (40 mg/kg body wt.) induce a blood pressure decrease with bradycardia, which is not transmitted through vagal efferents. These effects are due to an inhibition of sympathetic outflow to heart and vessels."}
{"id": "PMID:222558", "title": "Studies on the source of cyclic AMP in canine gastric juice.", "content": "The possibility that cyclic AMP in gastric juice is derived from plasma by simple clearance was evaluated. The effect of exogenous cyclic AMP administration (1 mg/min) on radioimmunoassayable cyclic AMP in plasma and gastric juice was studied in dog stomach during histamine (8--16 micrograms/kg/hr) infusion. Experiments were performed in vagally denervated fundic (Heidenhain) and in innervated gastric pouches. During infusion of cyclic AMP with histamine, plasma cyclic AMP concentration rapidly increased 500-fold. Simultaneously, gastric juice cyclic AMP levels decreased almost 50%. In contrast, dibutyryl cyclic AMP infusion increased gastric juice cAMP concentration 5-fold, suggesting that the gastric mucosa is more permeable to dibutyryl cyclic AMP. In Heidenhain pouch experiments the clearance of dibutyryl cyclic AMP into gastric juice was only 1.5% of the clearance of aminopyrine. It appears that plasma clearance of cyclic AMP fails to account for most of the cyclic AMP present in gastric juice.", "contents": "Studies on the source of cyclic AMP in canine gastric juice. The possibility that cyclic AMP in gastric juice is derived from plasma by simple clearance was evaluated. The effect of exogenous cyclic AMP administration (1 mg/min) on radioimmunoassayable cyclic AMP in plasma and gastric juice was studied in dog stomach during histamine (8--16 micrograms/kg/hr) infusion. Experiments were performed in vagally denervated fundic (Heidenhain) and in innervated gastric pouches. During infusion of cyclic AMP with histamine, plasma cyclic AMP concentration rapidly increased 500-fold. Simultaneously, gastric juice cyclic AMP levels decreased almost 50%. In contrast, dibutyryl cyclic AMP infusion increased gastric juice cAMP concentration 5-fold, suggesting that the gastric mucosa is more permeable to dibutyryl cyclic AMP. In Heidenhain pouch experiments the clearance of dibutyryl cyclic AMP into gastric juice was only 1.5% of the clearance of aminopyrine. It appears that plasma clearance of cyclic AMP fails to account for most of the cyclic AMP present in gastric juice."}
{"id": "PMID:222559", "title": "Effects of endogenous hyperglucagonemia on lower esophageal sphincter pressure and gastric acid secretion.", "content": "Lower esophageal sphincter function and gastric acid secretion were studied in a patient with endogenous hyperglucagonemia due to a functioning islet cell carcinoma. Complete resection of the tumor resulted in a fall of the serum concentration of immunoreactive glucagon to a normal level. Pre- and postoperative resting lower esophageal sphincter pressures and lower esophageal sphincter pressure responses to administration of pentagastrin, edrophonium, and bethanechol were unchanged. After surgery, preoperative immunoreactive glucagon concentrations were reproduced by intravenous infusion or intramuscular injection of exogenous glucagon. Lower esophageal sphincter resting pressures and responses to agonists were unchanged. In contrast, glucagon administered at 36 micrograms/kg/hr, which produced a serum concentration of immunoreactive glucagon (32,000 pg/ml) much greater than observed preoperatively (1200 pg/ml), diminished resting lower esophageal sphincter pressure and sphincter responses to pentagastrin, edrophonium, and bethanechol. Similarly, pentagastrin-stimulated gastric acid secretion was unaffected by tumor resection or low-dose glucagon infusion but was decreased at a glucagon infusion rate of 36 micrograms/kg/hr. This series of observations supports the thesis that endogenous glucagon plays no physiological role in the regulation of lower esophageal sphincter pressure or gastric acid secretion.", "contents": "Effects of endogenous hyperglucagonemia on lower esophageal sphincter pressure and gastric acid secretion. Lower esophageal sphincter function and gastric acid secretion were studied in a patient with endogenous hyperglucagonemia due to a functioning islet cell carcinoma. Complete resection of the tumor resulted in a fall of the serum concentration of immunoreactive glucagon to a normal level. Pre- and postoperative resting lower esophageal sphincter pressures and lower esophageal sphincter pressure responses to administration of pentagastrin, edrophonium, and bethanechol were unchanged. After surgery, preoperative immunoreactive glucagon concentrations were reproduced by intravenous infusion or intramuscular injection of exogenous glucagon. Lower esophageal sphincter resting pressures and responses to agonists were unchanged. In contrast, glucagon administered at 36 micrograms/kg/hr, which produced a serum concentration of immunoreactive glucagon (32,000 pg/ml) much greater than observed preoperatively (1200 pg/ml), diminished resting lower esophageal sphincter pressure and sphincter responses to pentagastrin, edrophonium, and bethanechol. Similarly, pentagastrin-stimulated gastric acid secretion was unaffected by tumor resection or low-dose glucagon infusion but was decreased at a glucagon infusion rate of 36 micrograms/kg/hr. This series of observations supports the thesis that endogenous glucagon plays no physiological role in the regulation of lower esophageal sphincter pressure or gastric acid secretion."}
{"id": "PMID:222560", "title": "Perforation of the colon associated with cytomegalovirus infection.", "content": "Cytomegalovirus (CMV) inclusions were found at colonic perforation sites in three patients with clinical settings suggesting a compromised immunologic status. This could be interpreted as: (1) CMV was an etiologic agent in these perforations; or (2) CMV was an opportunistic superinfection in areas of preexisting inflammation. To determine which interpretation was more likely, we examined material from these three and ten similar patients with colonic perforations, identifying any potential causative factors present. Eleven of the 13 patients had an identifiable cause of perforation, either tumor, diverticulitis, arteritis, or pancreatic pseudocyst, while two remained unexplained. If the presence of CMV merely represented an opportunistic superinfection, then all 13 should have been at equal risk of infection. However, CMV was present in only one of the 11 cases with another identifiable cause of perforation but was present in both of the cases without another cause. This is consistent with the hypothesis that CMV was in fact an etiologic or contributing factor in those cases where it was present. Other cases of CMV infection of the gastrointestinal tract were studied to determine the mechanism by which this infection could lead to perforation of a viscus. In our three cases with perforation, four additional cases of CMV infection of the colon which we have studied, and 30 other cases in the literature, CMV inclusions were found only in areas of ulceration or perforation, never in undamaged mucosa. Thus there is as yet no evidence that CMV can be a primary cause of colonic mucosal injury. It remains likely, however, that a mucosal injury due to another cause may be followed by CMV infection of the granulation tissue which then may lead to further injury and perforation.", "contents": "Perforation of the colon associated with cytomegalovirus infection. Cytomegalovirus (CMV) inclusions were found at colonic perforation sites in three patients with clinical settings suggesting a compromised immunologic status. This could be interpreted as: (1) CMV was an etiologic agent in these perforations; or (2) CMV was an opportunistic superinfection in areas of preexisting inflammation. To determine which interpretation was more likely, we examined material from these three and ten similar patients with colonic perforations, identifying any potential causative factors present. Eleven of the 13 patients had an identifiable cause of perforation, either tumor, diverticulitis, arteritis, or pancreatic pseudocyst, while two remained unexplained. If the presence of CMV merely represented an opportunistic superinfection, then all 13 should have been at equal risk of infection. However, CMV was present in only one of the 11 cases with another identifiable cause of perforation but was present in both of the cases without another cause. This is consistent with the hypothesis that CMV was in fact an etiologic or contributing factor in those cases where it was present. Other cases of CMV infection of the gastrointestinal tract were studied to determine the mechanism by which this infection could lead to perforation of a viscus. In our three cases with perforation, four additional cases of CMV infection of the colon which we have studied, and 30 other cases in the literature, CMV inclusions were found only in areas of ulceration or perforation, never in undamaged mucosa. Thus there is as yet no evidence that CMV can be a primary cause of colonic mucosal injury. It remains likely, however, that a mucosal injury due to another cause may be followed by CMV infection of the granulation tissue which then may lead to further injury and perforation."}
{"id": "PMID:222561", "title": "Prevalence of gallbladder disease in hyperlipoproteinemia.", "content": "An analysis of the occurrence of gallbladder disease (ie, cholelithiasis, cholecystitis, cholecystectomy) in 210 consecutive patients with primary hyperlipoproteinemia showed that the prevalence of gallbladder disease was 8%, 18%, and 42% in males with type IIa, IIb, and IV hyperlipoproteinemia, and 22%, 48%, and 72% in the corresponding groups of females. The 40-59-year-old patients were compared to three necropsy series from Malm\u00f6, Sweden. The occurrence of gallbladder disease was within normal limits in type IIa and abnormally high in type IV hyperlipoproteinemia. There were no differences with regard to age, body weight, glucose intolerance, or ischemic heart disease between type IV patients with and without GBD. It is suggested that certain forms of disturbances of lipoprotein metabolism are associated with an increased risk for development of gallbladder disease.", "contents": "Prevalence of gallbladder disease in hyperlipoproteinemia. An analysis of the occurrence of gallbladder disease (ie, cholelithiasis, cholecystitis, cholecystectomy) in 210 consecutive patients with primary hyperlipoproteinemia showed that the prevalence of gallbladder disease was 8%, 18%, and 42% in males with type IIa, IIb, and IV hyperlipoproteinemia, and 22%, 48%, and 72% in the corresponding groups of females. The 40-59-year-old patients were compared to three necropsy series from Malm\u00f6, Sweden. The occurrence of gallbladder disease was within normal limits in type IIa and abnormally high in type IV hyperlipoproteinemia. There were no differences with regard to age, body weight, glucose intolerance, or ischemic heart disease between type IV patients with and without GBD. It is suggested that certain forms of disturbances of lipoprotein metabolism are associated with an increased risk for development of gallbladder disease."}
{"id": "PMID:222557", "title": "Structure and function of photoreaction-centre chlorophyll.", "content": "Evidence from electron paramagnetic resonance (e.p.r.) studies suggests that the unpaired spin in oxidized P700+. or P865+. is shared by two special chlorophyll a (Chl a) or bacteriochlorophyll a (Bchl a) molecules respectively. Three classes of models have been proposed for special pair reaction centre chlorophyll: asymmetric, in which one Chl a (or Bchl a) acts as electron donor to a second acting as acceptor; models with translational symmetry only; and models with C2 symmetry. Models with C2 symmetry have been synthesized in vitro with two chlorophyll macrocycles tied together by a covalent link. The singlet and triplet states of the in vitro models have been characterized by e.p.r., nuclear magnetic resonance, and optical studies involving absorption, emission, and lasting behaviour. The fact that lasting occurs only from the folded configuration of the linked dimers suggests the availability of a highly effective nonradiative decay path from the S1 state of the excited open dimer. A radical-pair mechanism that accounts for the unusual spin polarization of the special pair triplet is proposed for the primary photochemistry in the reaction centre.", "contents": "Structure and function of photoreaction-centre chlorophyll. Evidence from electron paramagnetic resonance (e.p.r.) studies suggests that the unpaired spin in oxidized P700+. or P865+. is shared by two special chlorophyll a (Chl a) or bacteriochlorophyll a (Bchl a) molecules respectively. Three classes of models have been proposed for special pair reaction centre chlorophyll: asymmetric, in which one Chl a (or Bchl a) acts as electron donor to a second acting as acceptor; models with translational symmetry only; and models with C2 symmetry. Models with C2 symmetry have been synthesized in vitro with two chlorophyll macrocycles tied together by a covalent link. The singlet and triplet states of the in vitro models have been characterized by e.p.r., nuclear magnetic resonance, and optical studies involving absorption, emission, and lasting behaviour. The fact that lasting occurs only from the folded configuration of the linked dimers suggests the availability of a highly effective nonradiative decay path from the S1 state of the excited open dimer. A radical-pair mechanism that accounts for the unusual spin polarization of the special pair triplet is proposed for the primary photochemistry in the reaction centre."}
{"id": "PMID:222567", "title": "Pharmacology of bromocriptine in health and disease.", "content": "Bromocriptine, a lysergic acid derivative with a bromine atom at position 2, has been found to have unique effects on the dopamine receptors in the pituitary and central nervous system and peripherally. It is rapidly and completely absorbed from the gut and is mainly excreted in the bile and faeces. It seems to have a particular specificity for the pituitary prolactinotrophe although it does have other effects in different diseases states. In spite of the fact that it is an ergot derivative, it is remarkably free of ergot vascular side effects in the doses needed for therapeutic benefit. The most common adverse effect are nausea, vomiting and postural symptoms. These can be overcome by starting at low doses and increasing the therapeutic levels. Its major use is in the suppression of prolactin in states where this hormone is elevated irrespective of cause. It has also been used in the treatment of acromegaly and is under investigation for use in other disease states probably linked with prolactin system or dopaminergic receptors.", "contents": "Pharmacology of bromocriptine in health and disease. Bromocriptine, a lysergic acid derivative with a bromine atom at position 2, has been found to have unique effects on the dopamine receptors in the pituitary and central nervous system and peripherally. It is rapidly and completely absorbed from the gut and is mainly excreted in the bile and faeces. It seems to have a particular specificity for the pituitary prolactinotrophe although it does have other effects in different diseases states. In spite of the fact that it is an ergot derivative, it is remarkably free of ergot vascular side effects in the doses needed for therapeutic benefit. The most common adverse effect are nausea, vomiting and postural symptoms. These can be overcome by starting at low doses and increasing the therapeutic levels. Its major use is in the suppression of prolactin in states where this hormone is elevated irrespective of cause. It has also been used in the treatment of acromegaly and is under investigation for use in other disease states probably linked with prolactin system or dopaminergic receptors."}
{"id": "PMID:222569", "title": "The influence of normal human IgG and of thyroid-stimulating antibody (TSAb) on the binding of thyrotropin to thyroid plasma membranes.", "content": "The influence of serum IgG from normal and Graves' disease subjects on the binding of 125I-thyrotropin to isolated thyroid membranes was studied. IgG from either source inhibited binding in a concentration -dependent fashion. Human membranes were more sensitive to the human IgG than were bovine thyroid membranes and, when membranes were purified by discontinuous sucrose gradient centrifugation, they were more sensitive than were those less-purified, obtained by differential centrifugation. Using a Dixon plot, inhibition by normal IgG showed non-competitive kinetics. Fab fragments were more effective, on an equimolar basis, than was intact normal IgG, but were less potent when Graves' disease IgG was the parent molecule; this difference implies distinct modes of inhibition of thyrotropin-binding. The degree of inhibition by normal IgG was variable so that multiple control preparations are required to assess the additional effect characteristic of IgG from the subject with Graves' disease.", "contents": "The influence of normal human IgG and of thyroid-stimulating antibody (TSAb) on the binding of thyrotropin to thyroid plasma membranes. The influence of serum IgG from normal and Graves' disease subjects on the binding of 125I-thyrotropin to isolated thyroid membranes was studied. IgG from either source inhibited binding in a concentration -dependent fashion. Human membranes were more sensitive to the human IgG than were bovine thyroid membranes and, when membranes were purified by discontinuous sucrose gradient centrifugation, they were more sensitive than were those less-purified, obtained by differential centrifugation. Using a Dixon plot, inhibition by normal IgG showed non-competitive kinetics. Fab fragments were more effective, on an equimolar basis, than was intact normal IgG, but were less potent when Graves' disease IgG was the parent molecule; this difference implies distinct modes of inhibition of thyrotropin-binding. The degree of inhibition by normal IgG was variable so that multiple control preparations are required to assess the additional effect characteristic of IgG from the subject with Graves' disease."}
{"id": "PMID:222571", "title": "Inhibition of adenosine 3',5'-monophosphate accumulation and parathyroid hormone release by sodium nitroprusside.", "content": "Sodium nitroprusside effected a significant reduction in intracellular cAMP accumulation and parathyroid hormone release in dispersed bovine parathyroid cells. The inhibition was apparent at 3 x 10-4 M and maximal at 10-2 M nitroprusside. The effect was rapid and reversible and could be demonstrated in both the presence and absence of stimulating agonists [i.e. (-)isoproterenol, dopamine, and cholera toxin]. The inhibition was additive with that previously described for alpha-adrenergic agonists and prostaglandin F2 alpha and was not affected by phentolamine, suggesting that nitroprusside does not act through the inhibitory receptors previously described in this system. The nitroprusside effect on cAMP accumulation and parathyroid hormone release was present at virtually all concentrations of extracellular calcium tested; 2mM EGTA failed to prevent the inhibition. While extracellular calcium may play some role in this inhibition, it is not required for demonstration of the effect.", "contents": "Inhibition of adenosine 3',5'-monophosphate accumulation and parathyroid hormone release by sodium nitroprusside. Sodium nitroprusside effected a significant reduction in intracellular cAMP accumulation and parathyroid hormone release in dispersed bovine parathyroid cells. The inhibition was apparent at 3 x 10-4 M and maximal at 10-2 M nitroprusside. The effect was rapid and reversible and could be demonstrated in both the presence and absence of stimulating agonists [i.e. (-)isoproterenol, dopamine, and cholera toxin]. The inhibition was additive with that previously described for alpha-adrenergic agonists and prostaglandin F2 alpha and was not affected by phentolamine, suggesting that nitroprusside does not act through the inhibitory receptors previously described in this system. The nitroprusside effect on cAMP accumulation and parathyroid hormone release was present at virtually all concentrations of extracellular calcium tested; 2mM EGTA failed to prevent the inhibition. While extracellular calcium may play some role in this inhibition, it is not required for demonstration of the effect."}
{"id": "PMID:222574", "title": "The role of the carbohydrate in the stabilization, processing, and packaging of the glycosylated adrenocorticotropin-endorphin common precursor in toad pituitaries.", "content": "The neurointermediate lobes of dark adapted toads, Xenopus laevis, were incubated for 30 min in [3H]arginine, [3H]arginine plus [14C]glucosamine, or [3H]glucosamine and then chased for various time periods ranging from 1--3 h. The labeled polypeptides synthesized and secreted by the lobes were analyzed by acid-urea polyacrylamide gel electrophoresis. A glycosylated ACTH-endorphin precursor (32,000 mol wt) was synthesized during the pulse and identified by immunoprecipitation by ACTH-(11--24) antiserum. During the chase, this precursor was processed to various glycopeptides and peptides, including ACTH, beta-lipotropin, and alpha-MSH, which were subsequently secreted into the medium. An immunoprecipitable ACTH-related glycoprotein (approximately 150,000 mol wt) and other nonimmunoprecipitable glycoproteins (approximately 80,000--100,000 mol wt) were also synthesized and secreted by the neurointermediate lobe. The secretion of these glycoproteins and peptides was inhibited by dopamine. The significance of glycosylation of the precursor for the biosynthesis, processing, and secretion of the ACTH, beta-lipotropin-, and MSH-related peptides was examined by using a specific inhibitor of glycosylation, tunicamycin. Tunicamycin treatment did not affect the synthesis of the 32,000 mol wt ACTH-endorphin precursor but did prevent its glycosylation. The absence of carbohydrate on the precursor resulted in its rapid intracellular degradation. Precursors that escaped degradation were processed incompletely, leading to the formation and secretion of an unglycosylated intermediate and various other abnormal peptides. The data indicate that glycosylation of the ACTH-endorphin precursor may not be involved in the processes of intracellular transport, packaging, and secretion per se but, rather, may provide specific conformational stability to the precursor as a signal for directed limited proteolysis.", "contents": "The role of the carbohydrate in the stabilization, processing, and packaging of the glycosylated adrenocorticotropin-endorphin common precursor in toad pituitaries. The neurointermediate lobes of dark adapted toads, Xenopus laevis, were incubated for 30 min in [3H]arginine, [3H]arginine plus [14C]glucosamine, or [3H]glucosamine and then chased for various time periods ranging from 1--3 h. The labeled polypeptides synthesized and secreted by the lobes were analyzed by acid-urea polyacrylamide gel electrophoresis. A glycosylated ACTH-endorphin precursor (32,000 mol wt) was synthesized during the pulse and identified by immunoprecipitation by ACTH-(11--24) antiserum. During the chase, this precursor was processed to various glycopeptides and peptides, including ACTH, beta-lipotropin, and alpha-MSH, which were subsequently secreted into the medium. An immunoprecipitable ACTH-related glycoprotein (approximately 150,000 mol wt) and other nonimmunoprecipitable glycoproteins (approximately 80,000--100,000 mol wt) were also synthesized and secreted by the neurointermediate lobe. The secretion of these glycoproteins and peptides was inhibited by dopamine. The significance of glycosylation of the precursor for the biosynthesis, processing, and secretion of the ACTH, beta-lipotropin-, and MSH-related peptides was examined by using a specific inhibitor of glycosylation, tunicamycin. Tunicamycin treatment did not affect the synthesis of the 32,000 mol wt ACTH-endorphin precursor but did prevent its glycosylation. The absence of carbohydrate on the precursor resulted in its rapid intracellular degradation. Precursors that escaped degradation were processed incompletely, leading to the formation and secretion of an unglycosylated intermediate and various other abnormal peptides. The data indicate that glycosylation of the ACTH-endorphin precursor may not be involved in the processes of intracellular transport, packaging, and secretion per se but, rather, may provide specific conformational stability to the precursor as a signal for directed limited proteolysis."}
{"id": "PMID:222576", "title": "Anticonvulsant drug actions on in vitro and in vivo levels of cyclic AMP in the mouse brain.", "content": "Injections of pentylenetetrazol to mice produced a rise in steady state levels of cyclic AMP in the cerebrum and cerebellum subsequent to sacrifice by focused microwave irradiation. One hour pretreatment with anticonvulsant drugs--phenytoin, phenobarbital, carbamazepine, clonazepam, and diazepam--prevented this pentylenetetrazol-induced rise in cyclic AMP. Anticonvulsant agents which alone depressed steady state levels of cyclic AMP were phenytoin and carbamazepine in the cerebral cortex and carbamazepine in the cerebellum while elevations in the cyclic nucleotide were evoked by clonazepam in the cerebrum and cerebellum or diazepam and phenytoin in the cerebellum. Under in vitro conditions, in which incubated tissue slices of mouse cerebral cortex were used, the stimulation of cyclic AMP by norepinephrine was blocked by carbamazepine greater than phenobarbital greater than phenytoin. Inhibition of adenosine-induced accumulation of cyclic AMP was observed with phenobarbital greater than carbamazepine greater than phenytoin. Clonazepam enhanced this response to adenosine. Ouabain stimulation of cyclic AMP was prevented by carbamazepine, phenytoin greater than clonazepam greater than phenobarbital greater than diazepam. Only the highest concentrations (0.5 mM) of phenytoin, phenobarbital, and carbamazepine reduced the action of KCl on cyclic AMP elevation. Clonazepam and diazepam elevated the basal levels of the cyclic nucleotide.", "contents": "Anticonvulsant drug actions on in vitro and in vivo levels of cyclic AMP in the mouse brain. Injections of pentylenetetrazol to mice produced a rise in steady state levels of cyclic AMP in the cerebrum and cerebellum subsequent to sacrifice by focused microwave irradiation. One hour pretreatment with anticonvulsant drugs--phenytoin, phenobarbital, carbamazepine, clonazepam, and diazepam--prevented this pentylenetetrazol-induced rise in cyclic AMP. Anticonvulsant agents which alone depressed steady state levels of cyclic AMP were phenytoin and carbamazepine in the cerebral cortex and carbamazepine in the cerebellum while elevations in the cyclic nucleotide were evoked by clonazepam in the cerebrum and cerebellum or diazepam and phenytoin in the cerebellum. Under in vitro conditions, in which incubated tissue slices of mouse cerebral cortex were used, the stimulation of cyclic AMP by norepinephrine was blocked by carbamazepine greater than phenobarbital greater than phenytoin. Inhibition of adenosine-induced accumulation of cyclic AMP was observed with phenobarbital greater than carbamazepine greater than phenytoin. Clonazepam enhanced this response to adenosine. Ouabain stimulation of cyclic AMP was prevented by carbamazepine, phenytoin greater than clonazepam greater than phenobarbital greater than diazepam. Only the highest concentrations (0.5 mM) of phenytoin, phenobarbital, and carbamazepine reduced the action of KCl on cyclic AMP elevation. Clonazepam and diazepam elevated the basal levels of the cyclic nucleotide."}
{"id": "PMID:222577", "title": "Binding of adenosine 5'-monophosphate to bovine liver fructose 1,6-bisphosphatase.", "content": "Bovine liver fructose 1,6-bisphosphatase bound 4 mol of its allosteric inhibitor AMP per mole of enzyme with half-saturation at 17 mumol/l AMP. The presence of a mixture of positive and negative cooperativity in the binding of AMP to the enzyme was suggested by several procedures for analyzing binding data. In particular, calculation of the intrinsic binding constants for AMP yielded the relationships: K1' less than K2' greater than K3' less than K4', indicating mixed cooperativity.", "contents": "Binding of adenosine 5'-monophosphate to bovine liver fructose 1,6-bisphosphatase. Bovine liver fructose 1,6-bisphosphatase bound 4 mol of its allosteric inhibitor AMP per mole of enzyme with half-saturation at 17 mumol/l AMP. The presence of a mixture of positive and negative cooperativity in the binding of AMP to the enzyme was suggested by several procedures for analyzing binding data. In particular, calculation of the intrinsic binding constants for AMP yielded the relationships: K1' less than K2' greater than K3' less than K4', indicating mixed cooperativity."}
{"id": "PMID:222579", "title": "The effect of dephosphorylation on the properties of a helix-destabilizing protein from meiotic cells and its partial reversal by a protein kinase.", "content": "Properties of the helix-destabilizing protein from Lilium meiotic cells, 'R-protein', have been examined after treating it either with alkaline phosphatase or with two types of protein kinase. Dephosphorylation with the phosphatase increases binding capacity for single-strand DNA, but abolishes specificity of binding. Dephosphorylated R-protein binds equally to single and double-strand DNA. The capacity to facilitate denaturation or renaturation of DNA is also abolished by the treatment, but cooperativity characteristics are unaffected. The consequences of protein kinase treatment of native or dephosphorylated R-protein depend upon the origin of the kinase. Heterologous cyclic-AMP-dependent protein kinase cannot reverse the effects of dephosphorylation. However, it abolishes the binding affinity of either native or dephosphorylated R-protein for DNA. A protein kinase isolated from meiotic cells has no effect on the native protein, but it does restore all native properties tested to the dephosphorylated form after phosphorylating approximately two residues/molecule of protein.", "contents": "The effect of dephosphorylation on the properties of a helix-destabilizing protein from meiotic cells and its partial reversal by a protein kinase. Properties of the helix-destabilizing protein from Lilium meiotic cells, 'R-protein', have been examined after treating it either with alkaline phosphatase or with two types of protein kinase. Dephosphorylation with the phosphatase increases binding capacity for single-strand DNA, but abolishes specificity of binding. Dephosphorylated R-protein binds equally to single and double-strand DNA. The capacity to facilitate denaturation or renaturation of DNA is also abolished by the treatment, but cooperativity characteristics are unaffected. The consequences of protein kinase treatment of native or dephosphorylated R-protein depend upon the origin of the kinase. Heterologous cyclic-AMP-dependent protein kinase cannot reverse the effects of dephosphorylation. However, it abolishes the binding affinity of either native or dephosphorylated R-protein for DNA. A protein kinase isolated from meiotic cells has no effect on the native protein, but it does restore all native properties tested to the dephosphorylated form after phosphorylating approximately two residues/molecule of protein."}
{"id": "PMID:222581", "title": "A kinetic analysis of the uptake of cytosine-beta-D-arabinoside by rat-B77 cells. Differentiation between transport and phosphorylation.", "content": "We present here a differentiation by kinetic methods of the tandem processes of transport and metabolic during uptake of cytosine-beta-D-arabinoside by intact rat fibroblasts. Transport across the cell membrane occurs by a carrier-mediated mechanism displaying a Km of approximately 500 microM and a V of approximately pmol x min-1 x (10(6) cells)-1. The subsequent metabolic trapping (phosphorylation) has a Km of approximately 15 microM and V of approximately 0.25 pmol x min-1 x (10(6) cells)-1. In this system, transport is rate-limiting for the first phase of the uptake process whereas phosphorylation becomes rate-limiting when internal concentration of radioactive labeled substrate exceeds that in the extracellular medium. The duration of the first phase depends on the substrate concentration.", "contents": "A kinetic analysis of the uptake of cytosine-beta-D-arabinoside by rat-B77 cells. Differentiation between transport and phosphorylation. We present here a differentiation by kinetic methods of the tandem processes of transport and metabolic during uptake of cytosine-beta-D-arabinoside by intact rat fibroblasts. Transport across the cell membrane occurs by a carrier-mediated mechanism displaying a Km of approximately 500 microM and a V of approximately pmol x min-1 x (10(6) cells)-1. The subsequent metabolic trapping (phosphorylation) has a Km of approximately 15 microM and V of approximately 0.25 pmol x min-1 x (10(6) cells)-1. In this system, transport is rate-limiting for the first phase of the uptake process whereas phosphorylation becomes rate-limiting when internal concentration of radioactive labeled substrate exceeds that in the extracellular medium. The duration of the first phase depends on the substrate concentration."}
{"id": "PMID:222582", "title": "Effects of cytosol on transcription in isolated simian-virus-40-infected nuclei.", "content": "The transcription in vitro of nuclei isolated from monkey kidney cells infected with simian virus 40 was stimulated by a cytosol fraction from the same uninfected cells. Transcription in nuclei was inhibited 60--80% by 0.1 microgram/ml of alpha-amanitin, in the presence or in the absence of the cytosol preparation. Treatment of nuclei after transcription in vitro with 0.02 M EDTA preferentially solubilized viral-specific RNA partially bound to the viral chromatin. The increase in incorporation into total RNA seen in the presence of cytosol was not paralleled by any detectable increase in transcription of viral sequences as shown by RNA . DNA hybridizations.", "contents": "Effects of cytosol on transcription in isolated simian-virus-40-infected nuclei. The transcription in vitro of nuclei isolated from monkey kidney cells infected with simian virus 40 was stimulated by a cytosol fraction from the same uninfected cells. Transcription in nuclei was inhibited 60--80% by 0.1 microgram/ml of alpha-amanitin, in the presence or in the absence of the cytosol preparation. Treatment of nuclei after transcription in vitro with 0.02 M EDTA preferentially solubilized viral-specific RNA partially bound to the viral chromatin. The increase in incorporation into total RNA seen in the presence of cytosol was not paralleled by any detectable increase in transcription of viral sequences as shown by RNA . DNA hybridizations."}
{"id": "PMID:222585", "title": "Calf spleen NAD glycohydrolase. Comparison of the catalytic properties of the membrane-bound and the hydrosoluble forms of the enzyme.", "content": "The catalytic properties of membrane-bound calf spleen NAD glycohydrolase were studied in comparison with previous data obtained with a solubilized hydrosoluble form of the enzyme. When the hydrolysis of NAD catalyzed by membrane-bound NAD glycohydrolase was studied at pH values below 7.5, only insignificant interference by other NAD-hydrolyzing enzymes was detected, and no proton-diffusional inhibition was observed. The kinetics could, therefore, be followed using a titrimetric assay for NAD glycohydrolase activity. The effect of pH, ionic strength on the kinetic parameters, and shifts in binding constants for several ligands of the membrane-bound enzyme indicate that the NAD glycohydrolase activity is influenced by an electrostatic potential due to negative charges (polyelectrolyte effect). No significant changes in kinetic mechanism could be found between both NAD glycohydrolase forms. The association of the enzyme with the membrane results in a remarkably increased thermal stability, in changes in binding properties of the active site and in the emergence of new inhibitor binding sites; e.g. adenosine 3':5'-monophosphate (cyclic AMP) and adenosine, which do not inhibit the hydrosoluble form of NAD glycohydrolase, are good inhibitors (respectively competitive and mixed) of the membrane-bound enzyme. These data (i.e. allotopic changes) probably can be ascribed to enzyme conformational changes induced and stabilized by interaction with membrane constituents.", "contents": "Calf spleen NAD glycohydrolase. Comparison of the catalytic properties of the membrane-bound and the hydrosoluble forms of the enzyme. The catalytic properties of membrane-bound calf spleen NAD glycohydrolase were studied in comparison with previous data obtained with a solubilized hydrosoluble form of the enzyme. When the hydrolysis of NAD catalyzed by membrane-bound NAD glycohydrolase was studied at pH values below 7.5, only insignificant interference by other NAD-hydrolyzing enzymes was detected, and no proton-diffusional inhibition was observed. The kinetics could, therefore, be followed using a titrimetric assay for NAD glycohydrolase activity. The effect of pH, ionic strength on the kinetic parameters, and shifts in binding constants for several ligands of the membrane-bound enzyme indicate that the NAD glycohydrolase activity is influenced by an electrostatic potential due to negative charges (polyelectrolyte effect). No significant changes in kinetic mechanism could be found between both NAD glycohydrolase forms. The association of the enzyme with the membrane results in a remarkably increased thermal stability, in changes in binding properties of the active site and in the emergence of new inhibitor binding sites; e.g. adenosine 3':5'-monophosphate (cyclic AMP) and adenosine, which do not inhibit the hydrosoluble form of NAD glycohydrolase, are good inhibitors (respectively competitive and mixed) of the membrane-bound enzyme. These data (i.e. allotopic changes) probably can be ascribed to enzyme conformational changes induced and stabilized by interaction with membrane constituents."}
{"id": "PMID:222586", "title": "The dolichol pathway of protein glycosylation in rat liver. Stimulation by GTP of the incorporation of N-acetylglucosamine in endogenous lipids and proteins of rough microsomes treated with pyrophosphate.", "content": "Incorporation of N-acetylglucosamine into endogenous lipid and protein acceptors was investigated on heavy microsomes from rat liver, incubated with UDP-N-acetyl[14C]glucosamine and GDP-mannose in the absence of detergent. This subcellular preparation derived for 95% or more from the rough endoplasmic reticulum and was devoid of Golgi components which contain the enzyme that adds the peripheral N-acetylglucosamine units to glycoproteins. The label was found almost exclusively in dolichyl diphosphate N-acetylglucosamine, except when the subcellular preparation was treated with pyrophosphate and subsequently incubated with the nucleotide sugars in the presence of GTP. Then, the incorporation of N-acetylglucosamine was considerably enhanced, and the additional label was associated with dolichyl diphosphate N,N'-diacetylchitobiose, with dolichyl diphosphate oligosaccharides and with proteins. The time-course of N-acetylglucosamine incorporation in these products was compatible with the pathway of dolichyl diphosphate glycoconjugates for the biosynthesis of the core portion of saccharide chains linked to asparagine residues of glycoproteins. The addition of GDP-mannose to the incubation medium was required to produce labeled dolichyl diphosphate oligosaccharides, but not to incorporate N-acetylglucosamine in protein. It is concluded that rough microsomes are capable of assembling dolichol-linked oligosaccharides from exogenous nucleotide precursors and of transferring N,N'-diacetylchitobiose, or its mannosylated derivatives, from the lipid intermediate to endogenous proteins. However, these metabolic activities are hindered in the original subcellular preparation, and in the absence of GTP. Although the earliest perceptible effect produced jointly by the treatment with pyrophosphate and by GTP was the synthesis of dolichyl diphosphate N,N'-diacetylchitobiose, the primary action of these factors remains uncertain. They may stimulate directly the reaction forming dolichyl diphosphate N,N'-diacetylchitobiose from dolichyl diphosphate N-acetylglucosamine, or activate the synthesis of this latter intermediate from a particular pool of dolichyl monophosphate which is readily converted afterwards into disaccharide and oligosaccharide derivatives and glycosylates protein. The requirement for GTP might have a functional meaning, for GTP acted maximally at a concentration distinctly lower than its actual concentration in liver. The detachment of ribosomes from rough vesicles was the major alteration induced by treatment with pyrophosphate. It is suggested that the removal of ribosomes unmasks the membrane sites where GTP acts.", "contents": "The dolichol pathway of protein glycosylation in rat liver. Stimulation by GTP of the incorporation of N-acetylglucosamine in endogenous lipids and proteins of rough microsomes treated with pyrophosphate. Incorporation of N-acetylglucosamine into endogenous lipid and protein acceptors was investigated on heavy microsomes from rat liver, incubated with UDP-N-acetyl[14C]glucosamine and GDP-mannose in the absence of detergent. This subcellular preparation derived for 95% or more from the rough endoplasmic reticulum and was devoid of Golgi components which contain the enzyme that adds the peripheral N-acetylglucosamine units to glycoproteins. The label was found almost exclusively in dolichyl diphosphate N-acetylglucosamine, except when the subcellular preparation was treated with pyrophosphate and subsequently incubated with the nucleotide sugars in the presence of GTP. Then, the incorporation of N-acetylglucosamine was considerably enhanced, and the additional label was associated with dolichyl diphosphate N,N'-diacetylchitobiose, with dolichyl diphosphate oligosaccharides and with proteins. The time-course of N-acetylglucosamine incorporation in these products was compatible with the pathway of dolichyl diphosphate glycoconjugates for the biosynthesis of the core portion of saccharide chains linked to asparagine residues of glycoproteins. The addition of GDP-mannose to the incubation medium was required to produce labeled dolichyl diphosphate oligosaccharides, but not to incorporate N-acetylglucosamine in protein. It is concluded that rough microsomes are capable of assembling dolichol-linked oligosaccharides from exogenous nucleotide precursors and of transferring N,N'-diacetylchitobiose, or its mannosylated derivatives, from the lipid intermediate to endogenous proteins. However, these metabolic activities are hindered in the original subcellular preparation, and in the absence of GTP. Although the earliest perceptible effect produced jointly by the treatment with pyrophosphate and by GTP was the synthesis of dolichyl diphosphate N,N'-diacetylchitobiose, the primary action of these factors remains uncertain. They may stimulate directly the reaction forming dolichyl diphosphate N,N'-diacetylchitobiose from dolichyl diphosphate N-acetylglucosamine, or activate the synthesis of this latter intermediate from a particular pool of dolichyl monophosphate which is readily converted afterwards into disaccharide and oligosaccharide derivatives and glycosylates protein. The requirement for GTP might have a functional meaning, for GTP acted maximally at a concentration distinctly lower than its actual concentration in liver. The detachment of ribosomes from rough vesicles was the major alteration induced by treatment with pyrophosphate. It is suggested that the removal of ribosomes unmasks the membrane sites where GTP acts."}
{"id": "PMID:222587", "title": "Computer simulation of the fructose bisphosphatase/phosphofructokinase couple in rat liver.", "content": "Recycling of fructose 6-phosphate and fructose 1,6-bisphosphate in the rat liver under gluconeogenic and glycolytic conditions was investigated with a computer model containing representations of the kinetic properties of phosphofructokinase and fructose 1,6-bisphosphatase under realistic physiological conditions. The two enzyme submodels were constructed from data for the isolated enzymes in vitro by formal optimization. Tissue metabolite concentrations were corrected for cytosolic/mitochondrial compartmentation and effects of chelation and protonation equilibria. This model, which mostly considers the behavior of livers from starved rats, predicts negligible recycling under physiologically realistic conditions. Metabolic regulation of fructose 6-phosphate, the magnesium ion concentration and the distribution of adenine nucleotides appear to prevent operation of a 'futile cycle' in vivo. Rate-limiting chemical species were identified by sensitivity analysis.", "contents": "Computer simulation of the fructose bisphosphatase/phosphofructokinase couple in rat liver. Recycling of fructose 6-phosphate and fructose 1,6-bisphosphate in the rat liver under gluconeogenic and glycolytic conditions was investigated with a computer model containing representations of the kinetic properties of phosphofructokinase and fructose 1,6-bisphosphatase under realistic physiological conditions. The two enzyme submodels were constructed from data for the isolated enzymes in vitro by formal optimization. Tissue metabolite concentrations were corrected for cytosolic/mitochondrial compartmentation and effects of chelation and protonation equilibria. This model, which mostly considers the behavior of livers from starved rats, predicts negligible recycling under physiologically realistic conditions. Metabolic regulation of fructose 6-phosphate, the magnesium ion concentration and the distribution of adenine nucleotides appear to prevent operation of a 'futile cycle' in vivo. Rate-limiting chemical species were identified by sensitivity analysis."}
{"id": "PMID:222589", "title": "Methionyl-tRNA synthetase from Escherichia coli. Inactivation and labeling by periodate-treated initiator tRNA.", "content": "Both the aminoacylation and isotopic ATP-PPi exchange activities of native and trypsin-modified methionyl-tRNA synthetases from Escherichia coli are specifically inactivated by incubation in the presence of periodate-treated initiator tRNA Met. The inactivation proceeds through the formation of a reversible Schiff's base between the epsilon-amino group of a lysine within the catalytic center of the enzyme and the 2',3'-aldehyde groups created at the 3'-terminal ribose of tRNA. The Schiff's base may be stabilized by reduction with sodium borohydride. Intact tRNA Met f competes with the inactivation by its dialdehyde. It has been verified in the case of the modified enzyme that the protection is afforded according to an equilibrium constant identical to that for tRNA Met f binding at the active site of the enzyme. Finally it is shown that the incorporation of one molecule of the dialdehyde of [14C]tRNA completely destroys the activity of the monomeric trypsin-modified methionyl-tRNA synthetase.", "contents": "Methionyl-tRNA synthetase from Escherichia coli. Inactivation and labeling by periodate-treated initiator tRNA. Both the aminoacylation and isotopic ATP-PPi exchange activities of native and trypsin-modified methionyl-tRNA synthetases from Escherichia coli are specifically inactivated by incubation in the presence of periodate-treated initiator tRNA Met. The inactivation proceeds through the formation of a reversible Schiff's base between the epsilon-amino group of a lysine within the catalytic center of the enzyme and the 2',3'-aldehyde groups created at the 3'-terminal ribose of tRNA. The Schiff's base may be stabilized by reduction with sodium borohydride. Intact tRNA Met f competes with the inactivation by its dialdehyde. It has been verified in the case of the modified enzyme that the protection is afforded according to an equilibrium constant identical to that for tRNA Met f binding at the active site of the enzyme. Finally it is shown that the incorporation of one molecule of the dialdehyde of [14C]tRNA completely destroys the activity of the monomeric trypsin-modified methionyl-tRNA synthetase."}
{"id": "PMID:222590", "title": "Benign cystic nephroblastoma.", "content": "A benign cystic nephroblastoma in a 6-month-old boy is presented. Erroneous interpretation as malignant nephroblastoma led to unnecessarily aggressive therapy. There is no evidence of recurrence or metastatic disease 12 years after the initial resection. As shown in our case and in the others previously reported in the literature, benign cystic nephroblastoma represents a distinct clinicopathological entity which does not show malignant behavior.", "contents": "Benign cystic nephroblastoma. A benign cystic nephroblastoma in a 6-month-old boy is presented. Erroneous interpretation as malignant nephroblastoma led to unnecessarily aggressive therapy. There is no evidence of recurrence or metastatic disease 12 years after the initial resection. As shown in our case and in the others previously reported in the literature, benign cystic nephroblastoma represents a distinct clinicopathological entity which does not show malignant behavior."}
{"id": "PMID:222591", "title": "Adenylate kinase activity and glutathione concentration of cerebrospinal fluid in different neurological disorders.", "content": "Adenylate kinase activity and glutathione concentration were measured in cerebrospinal fluid (CSF) of 64 consecutive patients admitted for various neurological disorders. These two analyses were performed in addition to conventional examination of the CSF. Neurological symptoms most probably connected in some cases with no and in others with only subtle changes in the central nervous system were linked to no or only moderate activities of adenylate kinase together with no glutathione. 1 patient with meningioma had no adenylate kinase activity at all while 3 patients with malignant brain tumours showed clear activities similar to 3 patients with well established diagnoses of multiple sclerosis. On the contrary, glutathione was absent in CSF of the patients with brain tumours and multiple sclerosis. Various cerebrovascular diseases involving larger areas of the brain tissue resulted in clear adenylate kinase activities in CSF either alone as in 11 of the patients with cerebral infarction or in combination with the appearance of also glutathione as in the remaining 7 patients with cerebral infarction as well as in the 14 patients studied with hemorrhages of the brain.", "contents": "Adenylate kinase activity and glutathione concentration of cerebrospinal fluid in different neurological disorders. Adenylate kinase activity and glutathione concentration were measured in cerebrospinal fluid (CSF) of 64 consecutive patients admitted for various neurological disorders. These two analyses were performed in addition to conventional examination of the CSF. Neurological symptoms most probably connected in some cases with no and in others with only subtle changes in the central nervous system were linked to no or only moderate activities of adenylate kinase together with no glutathione. 1 patient with meningioma had no adenylate kinase activity at all while 3 patients with malignant brain tumours showed clear activities similar to 3 patients with well established diagnoses of multiple sclerosis. On the contrary, glutathione was absent in CSF of the patients with brain tumours and multiple sclerosis. Various cerebrovascular diseases involving larger areas of the brain tissue resulted in clear adenylate kinase activities in CSF either alone as in 11 of the patients with cerebral infarction or in combination with the appearance of also glutathione as in the remaining 7 patients with cerebral infarction as well as in the 14 patients studied with hemorrhages of the brain."}
{"id": "PMID:222593", "title": "Reversible abnormalities of low density lipoprotein composition in familial hypercholesterolaemia.", "content": "Low density lipoprotein (LDL) composition was analysed in twenty-one patients with familial hypercholesterolaemia, including six homozygotes. By comparison with nineteen controls the patients' LDL had an increased ratio of cholesterol:phospholipid and a decreased ratio of lecithin:sphingomyelin; these changes were more marked in homozygotes than in heterozygotes. Treatment of sevel patients with plasma exchange temporarily resulted in near-normalization of the composition of their LDL. These results suggest that abnormalities of LDL composition in familial hypercholesterolaemia are secondary to hypocatabolism of LDL, which prolongs the half-life of LDL and thus increases the mean age of the population of particles circulating in plasma.", "contents": "Reversible abnormalities of low density lipoprotein composition in familial hypercholesterolaemia. Low density lipoprotein (LDL) composition was analysed in twenty-one patients with familial hypercholesterolaemia, including six homozygotes. By comparison with nineteen controls the patients' LDL had an increased ratio of cholesterol:phospholipid and a decreased ratio of lecithin:sphingomyelin; these changes were more marked in homozygotes than in heterozygotes. Treatment of sevel patients with plasma exchange temporarily resulted in near-normalization of the composition of their LDL. These results suggest that abnormalities of LDL composition in familial hypercholesterolaemia are secondary to hypocatabolism of LDL, which prolongs the half-life of LDL and thus increases the mean age of the population of particles circulating in plasma."}
{"id": "PMID:222595", "title": "Mechanism of PGE inhibition of catecholamine release from adrenal medulla.", "content": "Catecholamine (CA) secretion from the adrenal medulla was induced in vitro by acetylcholine (10(-4)M) (ACh), by incubation in potassium-free medium, by addition of ouabain (10(-3)M), by theophylline (10(-2)M) or by salbutamol (10(-6) and 6 x 10(-6) M). Theophylline and salbutamol, but not ACh, released CA in a calcium-free medium supplemented with 2mM EGTA. PGE2 significantly inhibited both CA secretion evoked by ACh and that evoked by salbutamol, i.e. both secretion dependent on, and independent of, extracellular calcium, PGE2 counteracted the increase of cAMP levels caused by ACh or salbutamol in adrenal medullary slices. PGE2 also diminished the salbutamol-induced activation of adenylate cyclase in an adrenal medullary membrane preparation, PGE2 reduced the rate of 45Ca efflux from slices of adrenal medulla preloaded with 45CaCl2. It is suggested that PGE2 inhibits CA secretion through the following sequence: inhibition of adenylate cyclase, a fall of cellular cAMP resulting in reduced release of calcium from intracellular binding sites and reduced free cytoplasmic calcium.", "contents": "Mechanism of PGE inhibition of catecholamine release from adrenal medulla. Catecholamine (CA) secretion from the adrenal medulla was induced in vitro by acetylcholine (10(-4)M) (ACh), by incubation in potassium-free medium, by addition of ouabain (10(-3)M), by theophylline (10(-2)M) or by salbutamol (10(-6) and 6 x 10(-6) M). Theophylline and salbutamol, but not ACh, released CA in a calcium-free medium supplemented with 2mM EGTA. PGE2 significantly inhibited both CA secretion evoked by ACh and that evoked by salbutamol, i.e. both secretion dependent on, and independent of, extracellular calcium, PGE2 counteracted the increase of cAMP levels caused by ACh or salbutamol in adrenal medullary slices. PGE2 also diminished the salbutamol-induced activation of adenylate cyclase in an adrenal medullary membrane preparation, PGE2 reduced the rate of 45Ca efflux from slices of adrenal medulla preloaded with 45CaCl2. It is suggested that PGE2 inhibits CA secretion through the following sequence: inhibition of adenylate cyclase, a fall of cellular cAMP resulting in reduced release of calcium from intracellular binding sites and reduced free cytoplasmic calcium."}
{"id": "PMID:222596", "title": "Changes in brain levels of cyclic nucleotides and gamma-aminobutyric acid in barbiturate dependence and withdrawal.", "content": "Rats exposed to chronic intake of sodium barbital maintained high circulating levels of barbital in blood and brain and exhibited increased sensitivity ot audiogenic convulsions during the withdrawal period. Levels of gamma-aminobutyric acid (GABA), glutamate, guanosine 3',5'-monophosphate (cyclic GMP) and adenosine 3',5'-monophosphate (cyclic AMP) were measured in selected brain regions after sacrifice with high power microwave inactivation. Cyclic GMP during chronic barbital administration was significantly lower than controls in most brain regions, especially the hindbrain. During the withdrawal period cyclic GMP in the cerebellum was significantly increased, while returning at least to control levels in all other regions. GABA throughout the brain tended to be reduced during barbital dependence, while cyclic AMP and glutamate levels remained unchanged in all groups. These results indicate a possible role for cyclic GMP in the mediation of the central nervous system response during barbiturate dependence and withdrawal.", "contents": "Changes in brain levels of cyclic nucleotides and gamma-aminobutyric acid in barbiturate dependence and withdrawal. Rats exposed to chronic intake of sodium barbital maintained high circulating levels of barbital in blood and brain and exhibited increased sensitivity ot audiogenic convulsions during the withdrawal period. Levels of gamma-aminobutyric acid (GABA), glutamate, guanosine 3',5'-monophosphate (cyclic GMP) and adenosine 3',5'-monophosphate (cyclic AMP) were measured in selected brain regions after sacrifice with high power microwave inactivation. Cyclic GMP during chronic barbital administration was significantly lower than controls in most brain regions, especially the hindbrain. During the withdrawal period cyclic GMP in the cerebellum was significantly increased, while returning at least to control levels in all other regions. GABA throughout the brain tended to be reduced during barbital dependence, while cyclic AMP and glutamate levels remained unchanged in all groups. These results indicate a possible role for cyclic GMP in the mediation of the central nervous system response during barbiturate dependence and withdrawal."}
{"id": "PMID:222597", "title": "Modification by SQ 14225 of blood pressure and adrenal catecholamine response to hemorrhage.", "content": "SQ 14225 infusion to cats exposed to hemorrhage suppressed adrenomedullary catecholamine release. The immediate compensatory blood pressure response was unaffected, while the later compensatory response was of a higher magnitude in intact cats that in SQ 14225-treated animals. Adrenal gland blood flow was better preserved in SQ 14225-treated hemorrhaged cats than in cats exposed to hemorrhage only. These  data emphasize the role of angiotensin II in adrenal catecholamine and blood pressure responses to hemorrhage.", "contents": "Modification by SQ 14225 of blood pressure and adrenal catecholamine response to hemorrhage. SQ 14225 infusion to cats exposed to hemorrhage suppressed adrenomedullary catecholamine release. The immediate compensatory blood pressure response was unaffected, while the later compensatory response was of a higher magnitude in intact cats that in SQ 14225-treated animals. Adrenal gland blood flow was better preserved in SQ 14225-treated hemorrhaged cats than in cats exposed to hemorrhage only. These  data emphasize the role of angiotensin II in adrenal catecholamine and blood pressure responses to hemorrhage."}
{"id": "PMID:222599", "title": "Effects of monovalent cations on (Na+ + K+)-ATPase in rat brain slices.", "content": "The influence of monovalent cations on membrane (Na + K+)-ATPase was estimated in vitro in intact cells from the oxygen consumption of rat brain cortical slices. High concentrations of K+, Rb+ or Cs+ stimulated the respiration in the presence of Na+. This stimulation was antagonized by ouabain in a concentration- and time-dependent manner. Additionally, only combinations of monovalent cations, that stimulate (Na+ + K+)-ATPase, increased oxygen consumption, indicating that the stimulated portion of respiration is realted to the (Na+ + K+)-ATPase activity. Low concentrations of Rb+ and Cs+, however, failed to affect oxygen consumption. Li+ slightly and transiently stimulated oxygen uptake at low concentrations and inhibited it at higher concentrations. Low concentrations of Tl+ also stimulated respiration in a K+-free medium. However, the inhibitory effects of Tl+ were predominant at higher concentrations or in the presence of K+. Thus, monovalent cations can alter (Na+ + K+)-ATPase activity. While Rb+ and Li+ produce opposite effects on this enzyme system under certain conditions, these actions do not seem to be related to the antidepressant action of Rb+ and the antimanic action of Li+.", "contents": "Effects of monovalent cations on (Na+ + K+)-ATPase in rat brain slices. The influence of monovalent cations on membrane (Na + K+)-ATPase was estimated in vitro in intact cells from the oxygen consumption of rat brain cortical slices. High concentrations of K+, Rb+ or Cs+ stimulated the respiration in the presence of Na+. This stimulation was antagonized by ouabain in a concentration- and time-dependent manner. Additionally, only combinations of monovalent cations, that stimulate (Na+ + K+)-ATPase, increased oxygen consumption, indicating that the stimulated portion of respiration is realted to the (Na+ + K+)-ATPase activity. Low concentrations of Rb+ and Cs+, however, failed to affect oxygen consumption. Li+ slightly and transiently stimulated oxygen uptake at low concentrations and inhibited it at higher concentrations. Low concentrations of Tl+ also stimulated respiration in a K+-free medium. However, the inhibitory effects of Tl+ were predominant at higher concentrations or in the presence of K+. Thus, monovalent cations can alter (Na+ + K+)-ATPase activity. While Rb+ and Li+ produce opposite effects on this enzyme system under certain conditions, these actions do not seem to be related to the antidepressant action of Rb+ and the antimanic action of Li+."}
{"id": "PMID:222600", "title": "Decrease of cyclic GMP in cerebellar cortex by intrastriatal (--)-sulpiride.", "content": "Intraperitoneal administration of (--)-sulpiride (12 to 50 mg/kg) produced a dose-related decrease in cGMP content in cerebellar cortex, while the (+)-sulpiride (10 microgram), but not after intracerebellar injection. These findings support the contention that (--)-sulpiride modifies cerebellar cGMP levels through and action on striatal dopamine receptors.", "contents": "Decrease of cyclic GMP in cerebellar cortex by intrastriatal (--)-sulpiride. Intraperitoneal administration of (--)-sulpiride (12 to 50 mg/kg) produced a dose-related decrease in cGMP content in cerebellar cortex, while the (+)-sulpiride (10 microgram), but not after intracerebellar injection. These findings support the contention that (--)-sulpiride modifies cerebellar cGMP levels through and action on striatal dopamine receptors."}
{"id": "PMID:222622", "title": "An intracerebral, physiological role for angiotensin: effects of central blockade.", "content": "Although exogenous angiotensin II (AII) exerts a multitude of effects on the central nervous system, there is little evidence supporting a physiological role for the endogenously produced peptide. Some investigators have tested the hypothesis that AII is physiologically active in the brain with intracerebral infusions of blockers of the renin-angiotensin system. If blocker infusions produce effects that are opposite to exogenous AII infusions, it is evidence supporting a physiological role for endogenously generated angiotensin. Previous work has demonstrated that intraventricular infusion of AII elicits thirst and stimulates antidiuretic hormone and ACTH release. Intracerebral administration of AII also suppresses aldosterone secretion. Experiments that employed the blockers saralasin, a competitive inhibitor of AII, and SQ 20881, a converting enzyme blocker, are presented; results suggest that endogenous AII is involved in the control of thirst and peripheral hormone levels. Infusion of the blockers in the ventricular system led to changes in peripheral hormone concentrations opposite to that observed following infusions of AII.", "contents": "An intracerebral, physiological role for angiotensin: effects of central blockade. Although exogenous angiotensin II (AII) exerts a multitude of effects on the central nervous system, there is little evidence supporting a physiological role for the endogenously produced peptide. Some investigators have tested the hypothesis that AII is physiologically active in the brain with intracerebral infusions of blockers of the renin-angiotensin system. If blocker infusions produce effects that are opposite to exogenous AII infusions, it is evidence supporting a physiological role for endogenously generated angiotensin. Previous work has demonstrated that intraventricular infusion of AII elicits thirst and stimulates antidiuretic hormone and ACTH release. Intracerebral administration of AII also suppresses aldosterone secretion. Experiments that employed the blockers saralasin, a competitive inhibitor of AII, and SQ 20881, a converting enzyme blocker, are presented; results suggest that endogenous AII is involved in the control of thirst and peripheral hormone levels. Infusion of the blockers in the ventricular system led to changes in peripheral hormone concentrations opposite to that observed following infusions of AII."}
{"id": "PMID:222623", "title": "Evolutionary aspects of some neuropeptides.", "content": "The study of biologically active peptides is a study of structural homology and functional diversity. Some fundamental peptide structures used as chemical messengers by simple organisms were evidently maintained throughout evolution with little change. In higher organisms these structures may still be used for functions related to the original use as well as for very different purposes. Examples are given of the multifunctional roles of common peptides and of the mechanisms by means of which these functions are separated and regulated. The active core of ACTH appears to be used as a signal in regulation of reproduction throughout the range of eukaryotes and also appears in a baffling range of other important proteins. The ubiquitous nature of this peptide sequence suggests that it plays a universal role in recognition or activation of specific receptors. Peptides used in lower species as hormones or chemical defense substances play an important role in research as presagers of the discovery of corresponding mammalian peptides.", "contents": "Evolutionary aspects of some neuropeptides. The study of biologically active peptides is a study of structural homology and functional diversity. Some fundamental peptide structures used as chemical messengers by simple organisms were evidently maintained throughout evolution with little change. In higher organisms these structures may still be used for functions related to the original use as well as for very different purposes. Examples are given of the multifunctional roles of common peptides and of the mechanisms by means of which these functions are separated and regulated. The active core of ACTH appears to be used as a signal in regulation of reproduction throughout the range of eukaryotes and also appears in a baffling range of other important proteins. The ubiquitous nature of this peptide sequence suggests that it plays a universal role in recognition or activation of specific receptors. Peptides used in lower species as hormones or chemical defense substances play an important role in research as presagers of the discovery of corresponding mammalian peptides."}
{"id": "PMID:222624", "title": "Localization and possible function of peptidergic neurons and their interactions with central catecholamine neurons, and the central actions of gut hormones.", "content": "The localization of various neuropeptides is described in the gut and in the hypothalamus in the rat. Evidence is given for the presence of material resembling corticotropin-like intermediate peptide in arcuate and periarcuate neurons, projecting to various hypothalamic nuclei, limbic areas and the thalamus. beta-Endorphin and glucagon decrease dopamine turnover in the median eminence, while secretin increases dopamine turnover and vasoactive intestinal polypeptide (VIP) has no effect. beta-Endorphin, VIP, secretin, and glucagon all produce discrete changes in norepinephrine turnover in various hypothalamic nuclei. Mainly increases of norepinephrine turnover were observed. These catecholamine turnover changes appear to cause changes in the secretion of prolactin and growth hormone. The results therefore indicate that gut hormones and opioid peptides may act directly on the hypothalamus on specific types of receptors to participate in the control of hypothalamic functions such as control of hormone secretion from the anterior pituitary and of food intake. It seems possible that gastrointestinal peptides released from the gastrointestinal tract into the circulation under certain circumstances could reach the hypothalamus and modulate its activity via the above-mentioned mechanisms. It may therefore be speculated that disturbances in gastrointestinal functions could lead to pathological changes in food intake via modulation of hypothalamic activity.", "contents": "Localization and possible function of peptidergic neurons and their interactions with central catecholamine neurons, and the central actions of gut hormones. The localization of various neuropeptides is described in the gut and in the hypothalamus in the rat. Evidence is given for the presence of material resembling corticotropin-like intermediate peptide in arcuate and periarcuate neurons, projecting to various hypothalamic nuclei, limbic areas and the thalamus. beta-Endorphin and glucagon decrease dopamine turnover in the median eminence, while secretin increases dopamine turnover and vasoactive intestinal polypeptide (VIP) has no effect. beta-Endorphin, VIP, secretin, and glucagon all produce discrete changes in norepinephrine turnover in various hypothalamic nuclei. Mainly increases of norepinephrine turnover were observed. These catecholamine turnover changes appear to cause changes in the secretion of prolactin and growth hormone. The results therefore indicate that gut hormones and opioid peptides may act directly on the hypothalamus on specific types of receptors to participate in the control of hypothalamic functions such as control of hormone secretion from the anterior pituitary and of food intake. It seems possible that gastrointestinal peptides released from the gastrointestinal tract into the circulation under certain circumstances could reach the hypothalamus and modulate its activity via the above-mentioned mechanisms. It may therefore be speculated that disturbances in gastrointestinal functions could lead to pathological changes in food intake via modulation of hypothalamic activity."}
{"id": "PMID:222625", "title": "[Heart rate in cats during sleep after coagulation of the locus coeruleus].", "content": "The relationship between heart rate (HR) modulation and sleep mechanisms were analysed in 14 unrestrained cats with implanted electrodes and additional tripolar electrodes in the lateral geniculate nucleus and the abducens nucleus for recording the ponto--geniculo--occipital spikes. Anterior lesion of the locus coeruleus (LC) reduced the heart rate by about 18%, and a severe arrhythmia with augmented dispersion of R--R intervals occurred during paradoxical sleep (PS). Cats with posterior lesion had the heart rate increased by 20% and the spontaneous fluctuations of the R--R interval totally disappeared in them. The obtained data show that anterior and posterior LC exert different influences upon the heart rate fluctuations in sleep.", "contents": "[Heart rate in cats during sleep after coagulation of the locus coeruleus]. The relationship between heart rate (HR) modulation and sleep mechanisms were analysed in 14 unrestrained cats with implanted electrodes and additional tripolar electrodes in the lateral geniculate nucleus and the abducens nucleus for recording the ponto--geniculo--occipital spikes. Anterior lesion of the locus coeruleus (LC) reduced the heart rate by about 18%, and a severe arrhythmia with augmented dispersion of R--R intervals occurred during paradoxical sleep (PS). Cats with posterior lesion had the heart rate increased by 20% and the spontaneous fluctuations of the R--R interval totally disappeared in them. The obtained data show that anterior and posterior LC exert different influences upon the heart rate fluctuations in sleep."}
{"id": "PMID:222626", "title": "[Effect of parathyroid hormone on the myocardium in the presence of ouabain-induced reduced membrane ATPase activity].", "content": "The effect of parathyroid hormone (PTH) on the action potential of myocardium cells under conditions of the oubain--reduced activity of transport ATPase tells in reduced duration of the plateau and in increased amplitude of evoked potentials. The form of the AP alters on administration of the hormone against the background of expressed activity of the cardiac glycoside. The increase in the AP amplitude and the appearance of the \"peak\"preseding the plateau phase due to the hormone administration seem to be entailed by an action of the hormone upon the transport of sodium ions and activity of the membrane Na, K--dependent ATPase. The effect of PTH upon the contractile activity of the myocardium cells under the oubain influence becomes inverse: instead of a decrease in the contractions amplitude the hormone administration entails an elongation of the \"therapeutic\" phase of oubain action. The elongation also occurs after a preliminary work of the myocardium strip in the PTH solution. The effect seems to follow the increase of amount of calcium in the cell under the hormone effect.", "contents": "[Effect of parathyroid hormone on the myocardium in the presence of ouabain-induced reduced membrane ATPase activity]. The effect of parathyroid hormone (PTH) on the action potential of myocardium cells under conditions of the oubain--reduced activity of transport ATPase tells in reduced duration of the plateau and in increased amplitude of evoked potentials. The form of the AP alters on administration of the hormone against the background of expressed activity of the cardiac glycoside. The increase in the AP amplitude and the appearance of the \"peak\"preseding the plateau phase due to the hormone administration seem to be entailed by an action of the hormone upon the transport of sodium ions and activity of the membrane Na, K--dependent ATPase. The effect of PTH upon the contractile activity of the myocardium cells under the oubain influence becomes inverse: instead of a decrease in the contractions amplitude the hormone administration entails an elongation of the \"therapeutic\" phase of oubain action. The elongation also occurs after a preliminary work of the myocardium strip in the PTH solution. The effect seems to follow the increase of amount of calcium in the cell under the hormone effect."}
{"id": "PMID:222627", "title": "[Mechanism of dilatation of the thoracic duct upon stimulation of somatic nerves].", "content": "In acute experiments on 31 dogs, dilatation of the thoracic lymphatic duct on moderate (5--8 V) stimulation of afferents of the sciatic nerve and i. v. administration of noradrenaline (3--5 mcg/kg) was shown to be due to specific effects of excitation of the duct alpha-adrenoreceptors mainly. The alpha-adrenoreceptors seem to be represented in the thoracic duct in a much greater amount that the beta-adrenoreceptors. Stimulation of both types of the duct's adrenoreceptors leads to an increase in its capacity.", "contents": "[Mechanism of dilatation of the thoracic duct upon stimulation of somatic nerves]. In acute experiments on 31 dogs, dilatation of the thoracic lymphatic duct on moderate (5--8 V) stimulation of afferents of the sciatic nerve and i. v. administration of noradrenaline (3--5 mcg/kg) was shown to be due to specific effects of excitation of the duct alpha-adrenoreceptors mainly. The alpha-adrenoreceptors seem to be represented in the thoracic duct in a much greater amount that the beta-adrenoreceptors. Stimulation of both types of the duct's adrenoreceptors leads to an increase in its capacity."}
{"id": "PMID:222628", "title": "[Adrenergic and cholinergic mechanisms of the contractile reactions of major blood vessels].", "content": "Epinephrine, norepinephrine, and isoproterenol induced circular contraction of isolated segments of canine intracerebral internal carotid artery. The alpha--and beta-antagonists inhibited the effects of catecholamines. Acetylcholine showed dual effects involving both dilation (5.10(-12)--5.10(-9) g/ml) and contraction 5.10(-8) g/ml and higher). Atropine inhibited both effects. The K+ depolarization abolished the contractile effects of norepinephrine and acetylcholine. The blockade of calcium permeability by Mn++ abolished the contractile effects of sympathetic and parasympathetic mediators.", "contents": "[Adrenergic and cholinergic mechanisms of the contractile reactions of major blood vessels]. Epinephrine, norepinephrine, and isoproterenol induced circular contraction of isolated segments of canine intracerebral internal carotid artery. The alpha--and beta-antagonists inhibited the effects of catecholamines. Acetylcholine showed dual effects involving both dilation (5.10(-12)--5.10(-9) g/ml) and contraction 5.10(-8) g/ml and higher). Atropine inhibited both effects. The K+ depolarization abolished the contractile effects of norepinephrine and acetylcholine. The blockade of calcium permeability by Mn++ abolished the contractile effects of sympathetic and parasympathetic mediators."}
{"id": "PMID:222629", "title": "[Effect of creatine phosphate on the slow inward calcium current, action potentials and the strength of myocardial contraction].", "content": "The effect of creatine phosphate on the frog heart muscle involved maintenance of its contraction at high level even after inhibition of mitochondrial oxidative phosphorylation by sodium cyanide. The effect of creatine phosphate on the contractile force and action potential is similar for the frog heart ventricle and atrium. The voltage--clamp technique showed that creatine phosphate controlled the slow inward calcium current through the surface membrane of the frog atrium cells.", "contents": "[Effect of creatine phosphate on the slow inward calcium current, action potentials and the strength of myocardial contraction]. The effect of creatine phosphate on the frog heart muscle involved maintenance of its contraction at high level even after inhibition of mitochondrial oxidative phosphorylation by sodium cyanide. The effect of creatine phosphate on the contractile force and action potential is similar for the frog heart ventricle and atrium. The voltage--clamp technique showed that creatine phosphate controlled the slow inward calcium current through the surface membrane of the frog atrium cells."}
{"id": "PMID:222630", "title": "[Changes in the morpho-functional properties of gastric parietal cells during activation of secretory activity].", "content": "Electron--microscope and biochemical studies in rats and dogs showed that secretory membranes of parietal cells were in dynamic equilibrium with plasmalemma in activated secretion. During secretion, a transposition of secretory membranes occurs: 53.2% of tubulovesicular membranes transform into membranes of intracellular canaliculi and apical surface. K+--ATPace and carbonic anhydrase activities increased (55.5% and 62.9%, resp.). The system of secretory membranes and enzyme systems of parietal cells seem to take part synchronously in the process of gastric acid secretion.", "contents": "[Changes in the morpho-functional properties of gastric parietal cells during activation of secretory activity]. Electron--microscope and biochemical studies in rats and dogs showed that secretory membranes of parietal cells were in dynamic equilibrium with plasmalemma in activated secretion. During secretion, a transposition of secretory membranes occurs: 53.2% of tubulovesicular membranes transform into membranes of intracellular canaliculi and apical surface. K+--ATPace and carbonic anhydrase activities increased (55.5% and 62.9%, resp.). The system of secretory membranes and enzyme systems of parietal cells seem to take part synchronously in the process of gastric acid secretion."}
{"id": "PMID:222632", "title": "[Effect of etimizol, ethyrasol, and caffeine on the electrical activity of mollusk neurons].", "content": "In experiments on Limnae stagnalis neurons, ethymisol increased the AP duration while reducing the trace hyperpolarization and the rate of development of the AP descending phase. Ethymisol (10 mM/1) induced either hyperpolarization of neurons with an increase in membrane resistance or their depolarization (20 mM/1) with a decrease in membrane resistance. A drop in the medium temperature by 2-4 degrees C prevented the hyperpolarization. The ethymisol-induced hyperpolarization seems to be connected with a decrease in membrane permeability for sodium ions in resting conditions and with activation of electrogenic ion transport. The increase of extraneuronal potassium up to 4 mM/1 and depolarization induced by currents of 1-3 nA intensified the ethymisol effects. Ethymisol decreased efflux and influx of ions through membrane thus affecting the AP parameters. The effects of ethymisol also involved an increase of neurons excitability and intensification of synaptic activity. Neither ethyrasol nor caffein exerted these effects.", "contents": "[Effect of etimizol, ethyrasol, and caffeine on the electrical activity of mollusk neurons]. In experiments on Limnae stagnalis neurons, ethymisol increased the AP duration while reducing the trace hyperpolarization and the rate of development of the AP descending phase. Ethymisol (10 mM/1) induced either hyperpolarization of neurons with an increase in membrane resistance or their depolarization (20 mM/1) with a decrease in membrane resistance. A drop in the medium temperature by 2-4 degrees C prevented the hyperpolarization. The ethymisol-induced hyperpolarization seems to be connected with a decrease in membrane permeability for sodium ions in resting conditions and with activation of electrogenic ion transport. The increase of extraneuronal potassium up to 4 mM/1 and depolarization induced by currents of 1-3 nA intensified the ethymisol effects. Ethymisol decreased efflux and influx of ions through membrane thus affecting the AP parameters. The effects of ethymisol also involved an increase of neurons excitability and intensification of synaptic activity. Neither ethyrasol nor caffein exerted these effects."}
{"id": "PMID:222633", "title": "[Bioelectrical activity and ultrastructure of medicinal leech Retzius neurons during chronic direct and synaptic activation].", "content": "The threshold direct or synaptic 1/sec stimulation of the Retzius cells increases the firing rate of the neuron in the leach. The firing rate becomes synchronized with the stimulation applied. The membrane potential does not change. After 10 min of such stimulation changes occurring in the ultrastructure of neuron are similar to those in a neuron with no stimulation: these changes reveal a decrease in the synthetic processes whereas the bioelectrical activity remains the same which suggests a certain independence of the neuron electrophysiological parameters of its ultrastructure.", "contents": "[Bioelectrical activity and ultrastructure of medicinal leech Retzius neurons during chronic direct and synaptic activation]. The threshold direct or synaptic 1/sec stimulation of the Retzius cells increases the firing rate of the neuron in the leach. The firing rate becomes synchronized with the stimulation applied. The membrane potential does not change. After 10 min of such stimulation changes occurring in the ultrastructure of neuron are similar to those in a neuron with no stimulation: these changes reveal a decrease in the synthetic processes whereas the bioelectrical activity remains the same which suggests a certain independence of the neuron electrophysiological parameters of its ultrastructure."}
{"id": "PMID:222634", "title": "[Neural regulation of coronary circulation].", "content": "In anesthetized dogs, with the aid of catheterization and perfusion of the coronary arteries roith heporinesed blood, catheterization of the heart cavities, and synchronous recording of the hemodynamics in unopened thorax, the mechanisms of neural regulation of the coronary circulation were analysed. Tonic effects of the nervous system on the coronary vessels are insignificant, coronary resistance being maintained by the high basal tonus. The cholinergic and adrenergic mechaniseins interact with the more powerful metabolic mechanisms. The concrete interrelationships between the cholinergic and the adrenergic mechanisms in the heart adrenergic responses as well as their probable physiological significance, are discussed.", "contents": "[Neural regulation of coronary circulation]. In anesthetized dogs, with the aid of catheterization and perfusion of the coronary arteries roith heporinesed blood, catheterization of the heart cavities, and synchronous recording of the hemodynamics in unopened thorax, the mechanisms of neural regulation of the coronary circulation were analysed. Tonic effects of the nervous system on the coronary vessels are insignificant, coronary resistance being maintained by the high basal tonus. The cholinergic and adrenergic mechaniseins interact with the more powerful metabolic mechanisms. The concrete interrelationships between the cholinergic and the adrenergic mechanisms in the heart adrenergic responses as well as their probable physiological significance, are discussed."}
{"id": "PMID:222636", "title": "[Regulation of Na, K-ATPase activity in nerves during propagation of rhythmic excitation].", "content": "The changes of Na, K-ATPase activity of the isolated squid, crab, frog, and rat nerves depended on the stimulation frequency: at the frequency specific for each nerve the maximum deviation from initial resting level occurred. During a certain stimulation the maximum deviation of SH-group content and Na/K ratio as well as of Na, K-ATPase activity developed while the level of acetylcholine esterase activity (AEA) remained at its minimum. The data obtained suggest the mechanism of Na, K-ATPase activity in nerve under rhythmic propagation of excitation. In the resting nerve the minimum level of the acetylcholine concentration is kept because of the AEA. Under stimulation the membrane depolarization induces changes of the protein conformation suppressing the AEA. This results in an increase of the acetylcholine concentration in the nerve which leads to an increase of Na+ influx and K+ efflux. The changes of Na/K ratio in the nerve activate the transport ATPase.", "contents": "[Regulation of Na, K-ATPase activity in nerves during propagation of rhythmic excitation]. The changes of Na, K-ATPase activity of the isolated squid, crab, frog, and rat nerves depended on the stimulation frequency: at the frequency specific for each nerve the maximum deviation from initial resting level occurred. During a certain stimulation the maximum deviation of SH-group content and Na/K ratio as well as of Na, K-ATPase activity developed while the level of acetylcholine esterase activity (AEA) remained at its minimum. The data obtained suggest the mechanism of Na, K-ATPase activity in nerve under rhythmic propagation of excitation. In the resting nerve the minimum level of the acetylcholine concentration is kept because of the AEA. Under stimulation the membrane depolarization induces changes of the protein conformation suppressing the AEA. This results in an increase of the acetylcholine concentration in the nerve which leads to an increase of Na+ influx and K+ efflux. The changes of Na/K ratio in the nerve activate the transport ATPase."}
{"id": "PMID:222637", "title": "[Effect of adaptation to high-altitude hypoxia on the adrenoreactivity of the heart and the state of the adenyl cyclase and phosphodiesterase systems of the myocardium].", "content": "Experiments in white rats suggested that changes in activity of certain intracellular systems played a significant role in the mechanism of increasing adrenoreactivity of the heart in adaptation to high-altitude hypoxia.", "contents": "[Effect of adaptation to high-altitude hypoxia on the adrenoreactivity of the heart and the state of the adenyl cyclase and phosphodiesterase systems of the myocardium]. Experiments in white rats suggested that changes in activity of certain intracellular systems played a significant role in the mechanism of increasing adrenoreactivity of the heart in adaptation to high-altitude hypoxia."}
{"id": "PMID:222639", "title": "Mechanisms of inactivation of hypothalamic regulatory hormones.", "content": "The mechanisms of enzymic inactivation of thyrotropin-releasing hormone, luteinizing hormone-releasing hormone and somatostatin, the three fully-characterized hypothalamic regulatory hormones, and the possible physiological significance of the peptidases in neuroendocrine control has been reviewed. Application of the criteria of enzyme location (at the sites of biosynthesis, release, action, elimination and excretion), appropriate biochemical characteristics of the enzymes and changes in enzyme activity in physiological circumstances all suggest that the peptidases can contribute to the mechanisms controlling the hypothalamic hormones' release and actions. Besides their physiological function, the enzymes may also be directly involved in certain pathological conditions. There is evidence to indicate that the enzymes degrading the regulatory hormones may participate in the process of hormone activation as well as inactivation. A continuing investigation of the peptidases may lead to a better understanding of the established endocrine and other putative functions of these hypothalamic polypeptide hormones.", "contents": "Mechanisms of inactivation of hypothalamic regulatory hormones. The mechanisms of enzymic inactivation of thyrotropin-releasing hormone, luteinizing hormone-releasing hormone and somatostatin, the three fully-characterized hypothalamic regulatory hormones, and the possible physiological significance of the peptidases in neuroendocrine control has been reviewed. Application of the criteria of enzyme location (at the sites of biosynthesis, release, action, elimination and excretion), appropriate biochemical characteristics of the enzymes and changes in enzyme activity in physiological circumstances all suggest that the peptidases can contribute to the mechanisms controlling the hypothalamic hormones' release and actions. Besides their physiological function, the enzymes may also be directly involved in certain pathological conditions. There is evidence to indicate that the enzymes degrading the regulatory hormones may participate in the process of hormone activation as well as inactivation. A continuing investigation of the peptidases may lead to a better understanding of the established endocrine and other putative functions of these hypothalamic polypeptide hormones."}
{"id": "PMID:222640", "title": "Effects of carbamylcholine and ionophore A-23187 on cyclic 3',5'-AMP and cyclic 3',5'-GMP accumulation in dog-thyroid slices.", "content": "Carbamylcholine and acetylcholine through a muscarinic type of receptor, KCl, ionophore A-23187 and NaF increased cyclic GMP accumulation in dog-thyroid slices. These effects were abolished in calcium-depleted slices, which findings confirm that Ca2+ is required for cyclic GMP accumulation. All these agents depressed the accumulation of cyclic AMP in TSH-stimulated slices. KCl and NaF depressed cyclic AMP accumulation in TSH-treated slices even when they had been depleted of Ca2+. This suggests a cyclic GMP- and Ca2+-independent mechanism. The absence of inhibition of the effects of the ionophore, NaF and KCl in the presence of atropine suggests that these drugs do not act by inducing the release of acetylcholine in the slices. The effects of carbamylcholine and ionophore A-23187 on cyclic GMP accumulation and protein iodination were reversible; the inhibitions of TSH-induced cyclic AMP accumulation and secretion were non-competitive and were not accompanied by a depression of ATP levels. All these effects were greatly decreased in the absence of extracellular Ca2+. These data suggest that carbamylcholine and ionophore A-23187 act mainly by increasing the influx of extracellular Ca2+ in thyroid cells. However, the persistence of some carbamylcholine effect in the absence of Ca2+ in the medium suggests that this agent may also trigger the release of Ca2+ from an intrafollicular pool. The kinetics of action of carbamylcholine are compatible with a role of cyclic GMP in the inhibition of cyclic AMP accumulation. However, with the ionophore, the depression of cyclic AMP accumulation was much longer than the rise of cyclic GMP, which suggests a mechanism independent of cyclic GMP.", "contents": "Effects of carbamylcholine and ionophore A-23187 on cyclic 3',5'-AMP and cyclic 3',5'-GMP accumulation in dog-thyroid slices. Carbamylcholine and acetylcholine through a muscarinic type of receptor, KCl, ionophore A-23187 and NaF increased cyclic GMP accumulation in dog-thyroid slices. These effects were abolished in calcium-depleted slices, which findings confirm that Ca2+ is required for cyclic GMP accumulation. All these agents depressed the accumulation of cyclic AMP in TSH-stimulated slices. KCl and NaF depressed cyclic AMP accumulation in TSH-treated slices even when they had been depleted of Ca2+. This suggests a cyclic GMP- and Ca2+-independent mechanism. The absence of inhibition of the effects of the ionophore, NaF and KCl in the presence of atropine suggests that these drugs do not act by inducing the release of acetylcholine in the slices. The effects of carbamylcholine and ionophore A-23187 on cyclic GMP accumulation and protein iodination were reversible; the inhibitions of TSH-induced cyclic AMP accumulation and secretion were non-competitive and were not accompanied by a depression of ATP levels. All these effects were greatly decreased in the absence of extracellular Ca2+. These data suggest that carbamylcholine and ionophore A-23187 act mainly by increasing the influx of extracellular Ca2+ in thyroid cells. However, the persistence of some carbamylcholine effect in the absence of Ca2+ in the medium suggests that this agent may also trigger the release of Ca2+ from an intrafollicular pool. The kinetics of action of carbamylcholine are compatible with a role of cyclic GMP in the inhibition of cyclic AMP accumulation. However, with the ionophore, the depression of cyclic AMP accumulation was much longer than the rise of cyclic GMP, which suggests a mechanism independent of cyclic GMP."}
{"id": "PMID:222641", "title": "Prolactin receptors in primary cultures of carcinogen-induced rat-mammary tumors.", "content": "7,12-Dimethylbenz[alpha]anthracene-induced rat mammary tumors were dissociated with collagenase and hyaluronidase and placed into primary culture. In most cultures, specific binding of 125I-labeled ovine prolactin was (i) lower than that for the original tumors unless bovine prolactin (1 microgram/ml) had been added to the dissociation medium, and (ii) varied with the type of growth medium used. The level of prolactin binding in cultured cells was relatively constant for the first 7-10 days. Prolactin binding in cultured cell homogenates was maximal at pH 7.0, proportional to cell protein, specific for prolactin, and reached a steady state by 12 h at 22 degrees C. The half-maximum inhibition of 125I-labeled prolactin binding by unlabeled prolactin was 100 ng/ml for cells grown in 5-1000 ng of prolactin/ml. After prolactin was removed from the growth medium, the level of available binding sites progressively increased, reached a maximum at 48 h and then declined. At 48 h, the dissociation constant for prolactin binding (Kd approximately 1 x 10(-10) M) was comparable to that in tumors. In some cultured tumors, a 48-h treatment with 0.5 or 1.0 ng of prolactin/ml caused an apparent increase in the level of prolactin binding. Prolactin increased DNA synthesis and its removal caused a reduction in [3H]estradiol and [3H]-R5020 binding to cultured cell cytosols.", "contents": "Prolactin receptors in primary cultures of carcinogen-induced rat-mammary tumors. 7,12-Dimethylbenz[alpha]anthracene-induced rat mammary tumors were dissociated with collagenase and hyaluronidase and placed into primary culture. In most cultures, specific binding of 125I-labeled ovine prolactin was (i) lower than that for the original tumors unless bovine prolactin (1 microgram/ml) had been added to the dissociation medium, and (ii) varied with the type of growth medium used. The level of prolactin binding in cultured cells was relatively constant for the first 7-10 days. Prolactin binding in cultured cell homogenates was maximal at pH 7.0, proportional to cell protein, specific for prolactin, and reached a steady state by 12 h at 22 degrees C. The half-maximum inhibition of 125I-labeled prolactin binding by unlabeled prolactin was 100 ng/ml for cells grown in 5-1000 ng of prolactin/ml. After prolactin was removed from the growth medium, the level of available binding sites progressively increased, reached a maximum at 48 h and then declined. At 48 h, the dissociation constant for prolactin binding (Kd approximately 1 x 10(-10) M) was comparable to that in tumors. In some cultured tumors, a 48-h treatment with 0.5 or 1.0 ng of prolactin/ml caused an apparent increase in the level of prolactin binding. Prolactin increased DNA synthesis and its removal caused a reduction in [3H]estradiol and [3H]-R5020 binding to cultured cell cytosols."}
{"id": "PMID:222644", "title": "Calcific pancreatitis in a patient with type 5 hyperlipoproteinemia.", "content": "The history of a 27-year-old woman with 10 years of episodic abdominal pain and the development of calcific pancreatitis secondary to hyperlipoproteinemia is presented. The relationship between familial and alcoholic hyperlipidemia and pancreatitis is discussed as well as the mechanism of injury to the pancreas.", "contents": "Calcific pancreatitis in a patient with type 5 hyperlipoproteinemia. The history of a 27-year-old woman with 10 years of episodic abdominal pain and the development of calcific pancreatitis secondary to hyperlipoproteinemia is presented. The relationship between familial and alcoholic hyperlipidemia and pancreatitis is discussed as well as the mechanism of injury to the pancreas."}
{"id": "PMID:222645", "title": "Histocompatibility antigens in patients with hepatocellular carcinoma and their relationship to chronic hepatitis B virus infection in these patients.", "content": "Although hepatocellular carcinoma is probably caused by one or more environmental carcinogens, a genetically determined susceptibility to the development of the tumor has not been excluded. In looking for such a predisposition, we have compared the histocompatibility antigens (HLA) of 102 southern African blacks with histologically proved HCC with those of 208 healthy blacks. The standard two-stage lymphocyte microcytotoxicity method was used to test for 40 antigens: 17 in the A locus, 20 in the B locus, and 3 in the C locus. None of the HLA antigens had a frequency that was significantly different in the patients and the controls. A close association undoubtedly exists between chronic hepatitis B virus infection and hepatocellular carcinoma. If this virus is proved to be oncogenic with respect to hepatocellular carcinoma, a genetic predisposition to the hepatitis B virus carrier state may have an indirect bearing on the etiology of the tumor. Sera from the hepatocellular carcinoma patients were therefore tested for hepatitis B virus markers (HBV surface antigen and antibody against HBV core antigen), and these were related to the patients' histocompatibility antigens. None of the HLA antigen frequencies was significantly different in the surface antigen-positive and the surface antigen-negative patients. As 88% of the patients were anticore positive, no meaningful correlation could be carried out with this marker. Analysis of histocompatibility antigens thus failed to show evidence of a genetic predisposition either to hepatocellular carcinoma or to chronic hepatitis B surface antigenemia in patients with this tumor.", "contents": "Histocompatibility antigens in patients with hepatocellular carcinoma and their relationship to chronic hepatitis B virus infection in these patients. Although hepatocellular carcinoma is probably caused by one or more environmental carcinogens, a genetically determined susceptibility to the development of the tumor has not been excluded. In looking for such a predisposition, we have compared the histocompatibility antigens (HLA) of 102 southern African blacks with histologically proved HCC with those of 208 healthy blacks. The standard two-stage lymphocyte microcytotoxicity method was used to test for 40 antigens: 17 in the A locus, 20 in the B locus, and 3 in the C locus. None of the HLA antigens had a frequency that was significantly different in the patients and the controls. A close association undoubtedly exists between chronic hepatitis B virus infection and hepatocellular carcinoma. If this virus is proved to be oncogenic with respect to hepatocellular carcinoma, a genetic predisposition to the hepatitis B virus carrier state may have an indirect bearing on the etiology of the tumor. Sera from the hepatocellular carcinoma patients were therefore tested for hepatitis B virus markers (HBV surface antigen and antibody against HBV core antigen), and these were related to the patients' histocompatibility antigens. None of the HLA antigen frequencies was significantly different in the surface antigen-positive and the surface antigen-negative patients. As 88% of the patients were anticore positive, no meaningful correlation could be carried out with this marker. Analysis of histocompatibility antigens thus failed to show evidence of a genetic predisposition either to hepatocellular carcinoma or to chronic hepatitis B surface antigenemia in patients with this tumor."}
{"id": "PMID:222648", "title": "A genetically distinct form of cyclic AMP phosphodiesterase associated with chromomere 3D4 in Drosophila melanogaster.", "content": "Two cyclic AMP phosphodiesterase enzymes (E.C.3.1.4.17) are present in homogenates of adult Drosophila melanogaster. The two enzymes differ from one another in heat stability, affinity for Mg++, Ca++ activation and molecular weight. They do not differ markedly in their affinities for cyclic AMP, and both exhibit anomalous Michaelis-Menten kinetics. The more heat-labile enzyme is controlled in a dosage-dependent manner by chromomere 3D4 of the X chromosome and is absent in flies that are deficient for chromomere 3D4. Chromomere 3D4 is also necessary for the maintenance of normal cAMP levels, for male fertility, and for normal female fertility and oogenesis. The structural gene(s) for the more heat-stable enzyme is located outside of chromomeres 3C12-3D4. Whether 3D4 contains a structural gene, or a regulatory gene necessary for the presence of the labile enzyme, remains to be determined.", "contents": "A genetically distinct form of cyclic AMP phosphodiesterase associated with chromomere 3D4 in Drosophila melanogaster. Two cyclic AMP phosphodiesterase enzymes (E.C.3.1.4.17) are present in homogenates of adult Drosophila melanogaster. The two enzymes differ from one another in heat stability, affinity for Mg++, Ca++ activation and molecular weight. They do not differ markedly in their affinities for cyclic AMP, and both exhibit anomalous Michaelis-Menten kinetics. The more heat-labile enzyme is controlled in a dosage-dependent manner by chromomere 3D4 of the X chromosome and is absent in flies that are deficient for chromomere 3D4. Chromomere 3D4 is also necessary for the maintenance of normal cAMP levels, for male fertility, and for normal female fertility and oogenesis. The structural gene(s) for the more heat-stable enzyme is located outside of chromomeres 3C12-3D4. Whether 3D4 contains a structural gene, or a regulatory gene necessary for the presence of the labile enzyme, remains to be determined."}
{"id": "PMID:222649", "title": "Effects of dihydroergotoxine (Redergine) on the sleep-wakefulness cycle in the cat.", "content": "Investigations with dihydroergotoxine (DHE 1.0; 3.0 and 5.0 mg/kg i.p.) indicate that DHE exerts effect on the sleep-wakefulness cycle of the cat. In doses of 3.0 and 5.0 mg/kg i.p. DHE has a suppressant effect on sleep, and in particular on REM sleep, while wakefulness was increased. With a dose of 1.0 mg/kg, wakefulness and REM sleep were decreased, while slow-wave sleep was increased.", "contents": "Effects of dihydroergotoxine (Redergine) on the sleep-wakefulness cycle in the cat. Investigations with dihydroergotoxine (DHE 1.0; 3.0 and 5.0 mg/kg i.p.) indicate that DHE exerts effect on the sleep-wakefulness cycle of the cat. In doses of 3.0 and 5.0 mg/kg i.p. DHE has a suppressant effect on sleep, and in particular on REM sleep, while wakefulness was increased. With a dose of 1.0 mg/kg, wakefulness and REM sleep were decreased, while slow-wave sleep was increased."}
{"id": "PMID:222654", "title": "Platelet aggreation malondialdehyde formation in type IIA hypercholesterolemic patients.", "content": "Platelet aggregation induced by threshold concentrations of ADP, adrenaline, collagen and Thrombofax was evaluated in 25 type IIA hypercholesterolemic patients in comparison with 15 control subjects. Malondialdehyde (MDA) formation induced by collagen and thrombin was also studied in a subgroup of 8 patients. In the patient group, irreversible platelet aggregation was induced by significantly lower concentrations of both adrenaline (p is less than 0.05) and Thrombofax (p is less than 0.01). MDA formation induced by both aggregating agents was markedly increased (p is less than 0.01) in type IIA hypercholesterolemic patients.", "contents": "Platelet aggreation malondialdehyde formation in type IIA hypercholesterolemic patients. Platelet aggregation induced by threshold concentrations of ADP, adrenaline, collagen and Thrombofax was evaluated in 25 type IIA hypercholesterolemic patients in comparison with 15 control subjects. Malondialdehyde (MDA) formation induced by collagen and thrombin was also studied in a subgroup of 8 patients. In the patient group, irreversible platelet aggregation was induced by significantly lower concentrations of both adrenaline (p is less than 0.05) and Thrombofax (p is less than 0.01). MDA formation induced by both aggregating agents was markedly increased (p is less than 0.01) in type IIA hypercholesterolemic patients."}
{"id": "PMID:222655", "title": "Diagnostic and prognostic significance of electroencephalography with intravenous diazepam in epilepsy.", "content": "Thirty cases of intractable epilepsy in children were investigated to observe the correlation between the suppression of seizure discharges to intravenous diazepam and the type of seizure or effects of subsequent therapy. Suppression of seizure discharges were bilaterally poor in 75% of the cases with infantile spasms and 89% of cases with Lennox syndrome and other generalized seizures while it was unilaterally poor in 80% of the cases with focal or unilateral seizures. ACTH or steroid therapy was clinically and electroencephalographically effective in 80% of the cases with good suppression responses and in none of cases with good suppression that was resistant to the therapy. On the other hand, clinical seizures were not controlled in 73% of the cases showing poor suppression and EEG did not reveal improvement in 82% of the cases with poor suppression. EEG with intravenous diazepam is valuable for understanding the pharmacophysiological mechanism of epilepsy and it may be possible to select cases as candidates for ACTH or steroid therapy using this technique.", "contents": "Diagnostic and prognostic significance of electroencephalography with intravenous diazepam in epilepsy. Thirty cases of intractable epilepsy in children were investigated to observe the correlation between the suppression of seizure discharges to intravenous diazepam and the type of seizure or effects of subsequent therapy. Suppression of seizure discharges were bilaterally poor in 75% of the cases with infantile spasms and 89% of cases with Lennox syndrome and other generalized seizures while it was unilaterally poor in 80% of the cases with focal or unilateral seizures. ACTH or steroid therapy was clinically and electroencephalographically effective in 80% of the cases with good suppression responses and in none of cases with good suppression that was resistant to the therapy. On the other hand, clinical seizures were not controlled in 73% of the cases showing poor suppression and EEG did not reveal improvement in 82% of the cases with poor suppression. EEG with intravenous diazepam is valuable for understanding the pharmacophysiological mechanism of epilepsy and it may be possible to select cases as candidates for ACTH or steroid therapy using this technique."}
{"id": "PMID:222657", "title": "[Quantitative aspects of specific binding of cardiac glycosides to membrane receptors].", "content": "Although the exact mechanism of positive inotropic action of cardiac glycosides is unknown, specific membrane bound proteins with high affinity for this group of drugs have been characterized. These \"receptors\" for cardiac glycosides have been measured quantitatively in cardiac tissue of humans and several species as well as in other tissues. The occupation of receptors by cardioactive steroids has been found to agree quantitatively with the drug effects in respect to inhibition of (Na+ + K+)-ATPase and in respect to positive inotropy (these experiments were performed in electrically stimulated contracting cardiac muscle). Changes in receptor concentration or receptor properties have been observed in hyperthyroidism, chronic hypokalaemia, thalassaemia or in acutely changed serum concentrations of K+, Ca++ and several drugs. These changes may be of great significance in patients treated with cardiac glycosides as their effects are not reflected by the serum concentration of cardiac glycosides. The understanding of drug-receptor-interactions on the molecular level--especially under the pathological conditions in the patient--will increase our diagnostic and therapeutic knowledge.", "contents": "[Quantitative aspects of specific binding of cardiac glycosides to membrane receptors]. Although the exact mechanism of positive inotropic action of cardiac glycosides is unknown, specific membrane bound proteins with high affinity for this group of drugs have been characterized. These \"receptors\" for cardiac glycosides have been measured quantitatively in cardiac tissue of humans and several species as well as in other tissues. The occupation of receptors by cardioactive steroids has been found to agree quantitatively with the drug effects in respect to inhibition of (Na+ + K+)-ATPase and in respect to positive inotropy (these experiments were performed in electrically stimulated contracting cardiac muscle). Changes in receptor concentration or receptor properties have been observed in hyperthyroidism, chronic hypokalaemia, thalassaemia or in acutely changed serum concentrations of K+, Ca++ and several drugs. These changes may be of great significance in patients treated with cardiac glycosides as their effects are not reflected by the serum concentration of cardiac glycosides. The understanding of drug-receptor-interactions on the molecular level--especially under the pathological conditions in the patient--will increase our diagnostic and therapeutic knowledge."}
{"id": "PMID:222658", "title": "[Conservative treatment of peripheral nerve lesions].", "content": "Conservative treatment for cases of peripheral nerve damage may be subdivided into electrotherapy, positioning on splints and active as well as passive physiotherapy. Electrotherapy is generally carried out with exponential current which makes selective stimulation of the paralyzed muscles possible without stimulation of sensory fibres. The adjustment of the stimulation parameters, duration of stimulus and pause, gradient and stimulus intensity to the conditions of stimulation for each case is possible by determining the most favorable pulse duration. Successful electrotherapy depends upon an early beginning, the selective stimulation of the paralyzed muscles with exponential current at a sufficiently high intensity under isometric conditions and by avoiding overstretching of the muscles. Positioning of the extremities on splints in a functional position of the joints prevents overstretching of paralyzed muscles and thus contractures. Passive physiotherapy is indicated for the prevention or mobilisation of joint contractures. Active physiotherapy stimulates the regeneration of motor nerve fibres. The aim is a reintegration of the paralyzed muscles with the mobile muscles. Here the training of intact synergists, the innervation of antagonists and the activation of symmetrical healthy muscles of the contralateral extremity should be considered. The treatment of single nerve lesions with vitamin B does not appear reasonable.", "contents": "[Conservative treatment of peripheral nerve lesions]. Conservative treatment for cases of peripheral nerve damage may be subdivided into electrotherapy, positioning on splints and active as well as passive physiotherapy. Electrotherapy is generally carried out with exponential current which makes selective stimulation of the paralyzed muscles possible without stimulation of sensory fibres. The adjustment of the stimulation parameters, duration of stimulus and pause, gradient and stimulus intensity to the conditions of stimulation for each case is possible by determining the most favorable pulse duration. Successful electrotherapy depends upon an early beginning, the selective stimulation of the paralyzed muscles with exponential current at a sufficiently high intensity under isometric conditions and by avoiding overstretching of the muscles. Positioning of the extremities on splints in a functional position of the joints prevents overstretching of paralyzed muscles and thus contractures. Passive physiotherapy is indicated for the prevention or mobilisation of joint contractures. Active physiotherapy stimulates the regeneration of motor nerve fibres. The aim is a reintegration of the paralyzed muscles with the mobile muscles. Here the training of intact synergists, the innervation of antagonists and the activation of symmetrical healthy muscles of the contralateral extremity should be considered. The treatment of single nerve lesions with vitamin B does not appear reasonable."}
{"id": "PMID:222659", "title": "[Clinical and hemodynamic studies before and after mitral valve replacement (author's transl)].", "content": "Clinical and hemodynamic studies were carried out before and after replacement of stenotic mitral valves in 17 patients, 10 of whom received Bj\u00f6rk-Shiley (low profile mechanical) prostheses and 7 who received (porcine heterograft) bioprostheses. Mitral valve replacement led to amelioration of symptoms, improvement of phonocardiographic findings and, partially, to a lowering of pressure in the pulmonary circulation, augmentation of cardiac output, lessening of the pulmonary arteriolar and mitral valvular resistances as well as incrementation of mitral valve orifice area. Preexistent ECG changes, radiologic heart size, right ventricular filling pressure and stroke volume remained unaltered. In consideration of variables such as prosthetic size, severity of the disease and post-operative follow-up periods, the results obtained with both types of prostheses were comparable. The prostheses, however, inherently are responsible for a moderate degree of mitral stenosis which compromises exercise capacity and generally does not lead to normalization of pressure in the pulmonary circulation. Irreversible myocardial damage appears responsible for the fact that electrocardiographic abnormalities, the heart size, the right ventricular filling pressure and stroke volume remain unaltered postoperatively. Thus, patients who have undergone mitral valve replacement continue to require limitation of physical activities, a tailored medical regimen and close cardiologic follow-up.", "contents": "[Clinical and hemodynamic studies before and after mitral valve replacement (author's transl)]. Clinical and hemodynamic studies were carried out before and after replacement of stenotic mitral valves in 17 patients, 10 of whom received Bj\u00f6rk-Shiley (low profile mechanical) prostheses and 7 who received (porcine heterograft) bioprostheses. Mitral valve replacement led to amelioration of symptoms, improvement of phonocardiographic findings and, partially, to a lowering of pressure in the pulmonary circulation, augmentation of cardiac output, lessening of the pulmonary arteriolar and mitral valvular resistances as well as incrementation of mitral valve orifice area. Preexistent ECG changes, radiologic heart size, right ventricular filling pressure and stroke volume remained unaltered. In consideration of variables such as prosthetic size, severity of the disease and post-operative follow-up periods, the results obtained with both types of prostheses were comparable. The prostheses, however, inherently are responsible for a moderate degree of mitral stenosis which compromises exercise capacity and generally does not lead to normalization of pressure in the pulmonary circulation. Irreversible myocardial damage appears responsible for the fact that electrocardiographic abnormalities, the heart size, the right ventricular filling pressure and stroke volume remain unaltered postoperatively. Thus, patients who have undergone mitral valve replacement continue to require limitation of physical activities, a tailored medical regimen and close cardiologic follow-up."}
{"id": "PMID:222660", "title": "Glycerokinase in rat and human adipose tissue: response to hormonal and dietary stimuli.", "content": "Glycerokinase activity was measured in homogenates of rat and human adipocytes. Human adipocyte glycerokinase activity was not altered by various dietary and hormonal treatments. In contrast, glycerokinase activity in rat adipocytes was decreased by fasting 48 hr and returned toward normal levels after refeeding for 36 hr. This increase in enzyme activity during refeeding was blocked by prior administration of uromycin. Glycerokinase activity was also significantly increased following prolonged incubation of rat adipocytes with dexamethasone in vitro. This stimulation of glycerokinase was further augmented by the simultaneous addition of insulin. Glycerokinase activity in rat and human adipocytes was also dependent on the body weight of the respective tissue donor. Other data presented indicate that glycerokinase is not involved in the \"anti-lipolytic\" action of insulin. The possible metabolic significance of glycerokinase in adipose tissue is discussed.", "contents": "Glycerokinase in rat and human adipose tissue: response to hormonal and dietary stimuli. Glycerokinase activity was measured in homogenates of rat and human adipocytes. Human adipocyte glycerokinase activity was not altered by various dietary and hormonal treatments. In contrast, glycerokinase activity in rat adipocytes was decreased by fasting 48 hr and returned toward normal levels after refeeding for 36 hr. This increase in enzyme activity during refeeding was blocked by prior administration of uromycin. Glycerokinase activity was also significantly increased following prolonged incubation of rat adipocytes with dexamethasone in vitro. This stimulation of glycerokinase was further augmented by the simultaneous addition of insulin. Glycerokinase activity in rat and human adipocytes was also dependent on the body weight of the respective tissue donor. Other data presented indicate that glycerokinase is not involved in the \"anti-lipolytic\" action of insulin. The possible metabolic significance of glycerokinase in adipose tissue is discussed."}
{"id": "PMID:222661", "title": "Effects of thyrotoxicosis on mitochondrial enzymes of rat soleus.", "content": "Cytochrome oxidase, glycerol-3-phosphate dehydrogenase, and succinate dehydrogenase were measured in mitochondrial fractions obtained from rat soleus muscle of control and 8 week T3 + T4 treated animals. Under these conditions of prolonged treatment, there is a five-fold increase in the specific activities of both cytochrome oxidase and glycerole-3-phosphate dehydrogenase. Significant increases in total cellular mitochondrial content and enzyme activities were observed in T3 + T4 treated animals as compared to controls. These results indicate that thyrotoxicosis can induce selective changes in mitochondrial enzymes in slow twitch red (Type I) muscle fibers.", "contents": "Effects of thyrotoxicosis on mitochondrial enzymes of rat soleus. Cytochrome oxidase, glycerol-3-phosphate dehydrogenase, and succinate dehydrogenase were measured in mitochondrial fractions obtained from rat soleus muscle of control and 8 week T3 + T4 treated animals. Under these conditions of prolonged treatment, there is a five-fold increase in the specific activities of both cytochrome oxidase and glycerole-3-phosphate dehydrogenase. Significant increases in total cellular mitochondrial content and enzyme activities were observed in T3 + T4 treated animals as compared to controls. These results indicate that thyrotoxicosis can induce selective changes in mitochondrial enzymes in slow twitch red (Type I) muscle fibers."}
{"id": "PMID:222662", "title": "Evidence of adrenal 18-hydroxylase inhibition by metyrapone in man.", "content": "The influence of metyrapone (M) on the adrenal 18-hydroxylation was studied in two groups of healthy young men. In group I, serum concentrations of 18-OH-11-deoxycorticosterone (18-OH-DOC) fell significantly after a single oral dose of 40 mg/kg of M at 8.00 h, while those of 11-deoxycorticosterone (DOC) increased by a factor of about 500 within 4 hours after drug administration. Serum concentrations of 18-OH-DOC remained suppressed up to 14,00 h and tended to increase up to 16.00 h with a concomitant increase of plasma ACTH. In group II, serum concentrations of 18-OH-DOC and corticosterone (B) were slightly lowered eight hours after oral administration of 30 mg/kg of M at midnight in comparison with measurement of the previous day. Serum concentrations of 11-deoxycortisol (S) and DOC were markedly increased after drug administration. These findings indicate an inhibitory effect of M on adrenal 18-hydroxylation in addition to 11-hydroxylation under in vivo conditions. The slight increase of 18-OH-DOC at 16.00 h in group I and the only slight decrease of this steroid 8 hrs after drug administration in group II may be explained by declining enzyme blockade and a superimposed ACTH stimulation of the adrenal cortex at this time.", "contents": "Evidence of adrenal 18-hydroxylase inhibition by metyrapone in man. The influence of metyrapone (M) on the adrenal 18-hydroxylation was studied in two groups of healthy young men. In group I, serum concentrations of 18-OH-11-deoxycorticosterone (18-OH-DOC) fell significantly after a single oral dose of 40 mg/kg of M at 8.00 h, while those of 11-deoxycorticosterone (DOC) increased by a factor of about 500 within 4 hours after drug administration. Serum concentrations of 18-OH-DOC remained suppressed up to 14,00 h and tended to increase up to 16.00 h with a concomitant increase of plasma ACTH. In group II, serum concentrations of 18-OH-DOC and corticosterone (B) were slightly lowered eight hours after oral administration of 30 mg/kg of M at midnight in comparison with measurement of the previous day. Serum concentrations of 11-deoxycortisol (S) and DOC were markedly increased after drug administration. These findings indicate an inhibitory effect of M on adrenal 18-hydroxylation in addition to 11-hydroxylation under in vivo conditions. The slight increase of 18-OH-DOC at 16.00 h in group I and the only slight decrease of this steroid 8 hrs after drug administration in group II may be explained by declining enzyme blockade and a superimposed ACTH stimulation of the adrenal cortex at this time."}
{"id": "PMID:222664", "title": "Immunohistochemical localization of prolactin-binding sites in R3327 rat prostatic cancer cells.", "content": "Light microscope immunohistochemistry was used to test for and to localize prolactin-binding sites in the transplantable R3327 rat prostatic carcinoma. Fixed tissue sections of the tumor were first incubated with vehicle or varying concentrations of highly purified NIAMDD rat prolactin and then exposed to an immunoperoxidase staining sequence. Prolactin produced dose-related, immunospecific, staining in the cytoplasm of some neoplastic cells, indicative of intracellular prolactin-binding sites (IPBS). While cells with IPBS have been demonstrated in both differentiated and undifferentiated regions of this cancer, a role for prolactin in prostatic neoplasia, be it stimulatory or inhibitory, remains to be elucidated.", "contents": "Immunohistochemical localization of prolactin-binding sites in R3327 rat prostatic cancer cells. Light microscope immunohistochemistry was used to test for and to localize prolactin-binding sites in the transplantable R3327 rat prostatic carcinoma. Fixed tissue sections of the tumor were first incubated with vehicle or varying concentrations of highly purified NIAMDD rat prolactin and then exposed to an immunoperoxidase staining sequence. Prolactin produced dose-related, immunospecific, staining in the cytoplasm of some neoplastic cells, indicative of intracellular prolactin-binding sites (IPBS). While cells with IPBS have been demonstrated in both differentiated and undifferentiated regions of this cancer, a role for prolactin in prostatic neoplasia, be it stimulatory or inhibitory, remains to be elucidated."}
{"id": "PMID:222665", "title": "Cytophotometric DNA determination in human astroglial tumours.", "content": "The DNA content is determined by the cytophotometric method in 16 astroglial tumours, classified according to the degree of clinical malignancy. The values are compared to those found in non-tumoural astrocytes. This method appears to be more reliable in assessment of the degree of malignancy of the tumour in biopsy material than histological criteria and the mitotic index. It is also shown to be of great value in cases where the biopsy is taken at the margin of the tumour and in which malignant histological features are missing.", "contents": "Cytophotometric DNA determination in human astroglial tumours. The DNA content is determined by the cytophotometric method in 16 astroglial tumours, classified according to the degree of clinical malignancy. The values are compared to those found in non-tumoural astrocytes. This method appears to be more reliable in assessment of the degree of malignancy of the tumour in biopsy material than histological criteria and the mitotic index. It is also shown to be of great value in cases where the biopsy is taken at the margin of the tumour and in which malignant histological features are missing."}
{"id": "PMID:222666", "title": "COPE: a systematic approach to moving chronic patients into the community.", "content": "COPE, a program designed to help chronic psychiatric patients make the transition from institutionalization to independent living in the community, emphasizes both in-hospital training the systematic aftercare as two points on a continuum of treatment. The program includes four training phases, with each phase based upon the skills acquired in the preceding one. The residents are thereby assured of having the necessary skills for progressing to more complex tasks as they proceed through the program. During the last phase, support by the mental health system is gradually replaced by help from community support systems.", "contents": "COPE: a systematic approach to moving chronic patients into the community. COPE, a program designed to help chronic psychiatric patients make the transition from institutionalization to independent living in the community, emphasizes both in-hospital training the systematic aftercare as two points on a continuum of treatment. The program includes four training phases, with each phase based upon the skills acquired in the preceding one. The residents are thereby assured of having the necessary skills for progressing to more complex tasks as they proceed through the program. During the last phase, support by the mental health system is gradually replaced by help from community support systems."}
{"id": "PMID:222668", "title": "Oligodactyly and multiple synostoses of the extremities: two cases in sibs. A variant of Cenani-Lenz syndactyly.", "content": "Two sibs with a rare phenotype of oligodactyly with metacarpal, carpal, radioulnar, and metatarsal synostoses and shortening of the forearms were born of healthy parents. Genetic counselling with regard to future children of one of these sibs was given on the assumption of an autosomal recessive inheritance, which is highly probable, judging from the other rare familial cases found in the literature.", "contents": "Oligodactyly and multiple synostoses of the extremities: two cases in sibs. A variant of Cenani-Lenz syndactyly. Two sibs with a rare phenotype of oligodactyly with metacarpal, carpal, radioulnar, and metatarsal synostoses and shortening of the forearms were born of healthy parents. Genetic counselling with regard to future children of one of these sibs was given on the assumption of an autosomal recessive inheritance, which is highly probable, judging from the other rare familial cases found in the literature."}
{"id": "PMID:222669", "title": "Organ culture of adult mouse intestine. I. Morphological results after 24 and 48 hours of culture.", "content": "Explants of adult mouse intestine have been maintained in organ culture for 24 to 48 hr. The best results have been obtained with a mixture of DMEM-HEPES medium and NCTC-135 enriched with 10% fetal bovine serum. The morphology of the mucosa is well preserved at the light and electron microscopic level: absorbing cells exhibit an increase in secondary lysosomes; goblet cells and Paneth cells remain active; numerous mitoses are observed in the crypts; and vigorous re-epithelization takes place on the margin of the explants.", "contents": "Organ culture of adult mouse intestine. I. Morphological results after 24 and 48 hours of culture. Explants of adult mouse intestine have been maintained in organ culture for 24 to 48 hr. The best results have been obtained with a mixture of DMEM-HEPES medium and NCTC-135 enriched with 10% fetal bovine serum. The morphology of the mucosa is well preserved at the light and electron microscopic level: absorbing cells exhibit an increase in secondary lysosomes; goblet cells and Paneth cells remain active; numerous mitoses are observed in the crypts; and vigorous re-epithelization takes place on the margin of the explants."}
{"id": "PMID:222670", "title": "Effect of in vitro cultivation and Mycoplasma pneumoniae infection on intracellular cyclic AMP levels in hamster tracheal organ cultures.", "content": "Exogenous cyclic AMP and dibutyryl cyclic AMP decreased the relative ciliary activity values of tracheal organ cultures. In contrast, theophylline and cholera toxin were not ciliostatic. The use of a radioimmunoassay for cyclic AMP indicated that all of the tested substances increased intracellular cyclic AMP levels to some extent (from 3-fold for cholera toxin to almost 40-fold for dibutyryl cyclic AMP). Physical inactivation of explants by either freeze-thaw or heat destroyed all ciliary activity and greatly decreased intracellular cyclic AMP levels. Cyclic AMP levels of explants remained relatively constant during in vitro cultivation. Three strains of Mycoplasma pneumoniae were found to contain extremely low amounts of cyclic AMP. Infection of tracheal explants produced a significant decrease in relative ciliary activity, but only a slight decline in organ-culture cyclic AMP levels.", "contents": "Effect of in vitro cultivation and Mycoplasma pneumoniae infection on intracellular cyclic AMP levels in hamster tracheal organ cultures. Exogenous cyclic AMP and dibutyryl cyclic AMP decreased the relative ciliary activity values of tracheal organ cultures. In contrast, theophylline and cholera toxin were not ciliostatic. The use of a radioimmunoassay for cyclic AMP indicated that all of the tested substances increased intracellular cyclic AMP levels to some extent (from 3-fold for cholera toxin to almost 40-fold for dibutyryl cyclic AMP). Physical inactivation of explants by either freeze-thaw or heat destroyed all ciliary activity and greatly decreased intracellular cyclic AMP levels. Cyclic AMP levels of explants remained relatively constant during in vitro cultivation. Three strains of Mycoplasma pneumoniae were found to contain extremely low amounts of cyclic AMP. Infection of tracheal explants produced a significant decrease in relative ciliary activity, but only a slight decline in organ-culture cyclic AMP levels."}
{"id": "PMID:222674", "title": "Quantitative immunoelectrophoretic analysis of human antibodies against herpes simplex virus antigens.", "content": "By use of crossed immunoelectrophoresis with intermediate gel, antidbody titers against six individual herpes simplex virus (HSV) glycoproteins and two nonglycosylated proteins were determined in 100 human sera. High antibody titers were found against two different HSV type-common glycoproteins designated Ag8 and Ag11 (containing glycosylated polypeptides D and B, respectively). The anti-Ag8 and -Ag11 titers correlated with HSV neutralizing antibody titers. Most of the serological cross-reactivity between HSV type 1 and type 2 was probably caused by antibodies to Ag8 and Ag11. Human antibodies against one HSV type 1-specific glycoprotein (Ag6, containing glycosylated polypeptide C) and two HSV type 2 glycoproteins (Ag4 and Ag9) were also demonstrated, and the titers correlated better with neutralizing antibody titers of the homologous than of the heterologous virus type. The data presented can be directly applied to the further development of diagnostic reagents.", "contents": "Quantitative immunoelectrophoretic analysis of human antibodies against herpes simplex virus antigens. By use of crossed immunoelectrophoresis with intermediate gel, antidbody titers against six individual herpes simplex virus (HSV) glycoproteins and two nonglycosylated proteins were determined in 100 human sera. High antibody titers were found against two different HSV type-common glycoproteins designated Ag8 and Ag11 (containing glycosylated polypeptides D and B, respectively). The anti-Ag8 and -Ag11 titers correlated with HSV neutralizing antibody titers. Most of the serological cross-reactivity between HSV type 1 and type 2 was probably caused by antibodies to Ag8 and Ag11. Human antibodies against one HSV type 1-specific glycoprotein (Ag6, containing glycosylated polypeptide C) and two HSV type 2 glycoproteins (Ag4 and Ag9) were also demonstrated, and the titers correlated better with neutralizing antibody titers of the homologous than of the heterologous virus type. The data presented can be directly applied to the further development of diagnostic reagents."}
{"id": "PMID:222675", "title": "Effect of tobacco smoking on the functions of polymorphonuclear leukocytes.", "content": "Eight tests investigating the function of circulating polymorphonuclear leukocytes were performed in 68 subjects, half of whom smoked at least 20 cigarettes per day. Comparison of the two groups allowed determination of the in vivo effect of tobacco smoke on the nonspecific defense system of the body. Ingestion ability, oxygen consumption, and bactericidal activity were normal in smokers. Myeloperoxidase and neutrophil alkaline phosphatase activities also were unchanged. The nitroblue tetrazolium reduction and the serum lysozyme levels were slightly increased in smokers. The capillary tube random migration, though, was depressed, and intensive smoking further aggravated this change. It is suggested that tobacco smoke acts directly on one (or several) unidentified target site of polymorphonuclear leukocytes. This impairment, demonstrated in vivo, probably plays a role in the genesis of the bronchopulmonary diseases so frequent in heavy smokers.", "contents": "Effect of tobacco smoking on the functions of polymorphonuclear leukocytes. Eight tests investigating the function of circulating polymorphonuclear leukocytes were performed in 68 subjects, half of whom smoked at least 20 cigarettes per day. Comparison of the two groups allowed determination of the in vivo effect of tobacco smoke on the nonspecific defense system of the body. Ingestion ability, oxygen consumption, and bactericidal activity were normal in smokers. Myeloperoxidase and neutrophil alkaline phosphatase activities also were unchanged. The nitroblue tetrazolium reduction and the serum lysozyme levels were slightly increased in smokers. The capillary tube random migration, though, was depressed, and intensive smoking further aggravated this change. It is suggested that tobacco smoke acts directly on one (or several) unidentified target site of polymorphonuclear leukocytes. This impairment, demonstrated in vivo, probably plays a role in the genesis of the bronchopulmonary diseases so frequent in heavy smokers."}
{"id": "PMID:222676", "title": "Polymyxin B sulfate modification of bacterial endotoxin: effects on the development of endotoxin shock in dogs.", "content": "The effects of endotoxin (lipopolysaccharide [LPS]) on the pathogenesis of canine endotoxin shock were compared with those of LPS which had interacted with polymyxin B sulfate prior to administration. Both LPS and polymyxin B-modified LPS caused comparable early decreases in aortic blood pressure, leukocyte and platelet numbers, and serum complement levels. However, in dogs receiving polymyxin B-modified LPS the late hypotensive phase was significantly ameliorated and lethality was significantly decreased. These data indicate that polymyxin B-modified LPS, though significantly less lethal than unmodified LPS, was capable of major interactions with several components of the humoral defense system, and support the concept that such interactions are not determinative in the pathogenesis of canine endotoxin shock.", "contents": "Polymyxin B sulfate modification of bacterial endotoxin: effects on the development of endotoxin shock in dogs. The effects of endotoxin (lipopolysaccharide [LPS]) on the pathogenesis of canine endotoxin shock were compared with those of LPS which had interacted with polymyxin B sulfate prior to administration. Both LPS and polymyxin B-modified LPS caused comparable early decreases in aortic blood pressure, leukocyte and platelet numbers, and serum complement levels. However, in dogs receiving polymyxin B-modified LPS the late hypotensive phase was significantly ameliorated and lethality was significantly decreased. These data indicate that polymyxin B-modified LPS, though significantly less lethal than unmodified LPS, was capable of major interactions with several components of the humoral defense system, and support the concept that such interactions are not determinative in the pathogenesis of canine endotoxin shock."}
{"id": "PMID:222677", "title": "Suppression of in vitro antibody response by spleen cells of mice infected with Friend-associated lymphatic leukemia virus.", "content": "The ability of spleen cells of mice infected with oncornaviruses to depress the in vitro antibody responsiveness of normal lymphoid cells was exploited in an attempt to clarify the role played by the lymphatic leukemia virus (LLV) component in the immunodepressive properties of the Friend leukemia complex. Spleen cells of mice infected with LLV or, for comparison, with the entire complex were added to cultures of sheep erythrocyte-primed uninfected spleen cells, and the antibody-forming cells produced by the latter, after antigen restimulation, were assayed. The addition within 2 days from culture initiation of low numbers of cells infected with either virus preparation suppressed all stages of the response affecting the production of both immunoglobulin M and immunoglobulin G antibody. The activity of infected cells resisted doses of ultraviolet radiation which inhibit cell multiplication but was abolished by disrupting the cells and was prevented by the presence of anti-LLV antibodies. The LLV-infected spleen cells responsible for suppression were not removed by treatments which selectively remove or kill macrophages and exhibited surface properties of B lymphocytes. These results were interpreted as indicating that the effect is due to virus (or viral products) released by B cells. The suppressing cells in the spleens of mice in the early days of Friend leukemia complex infection presented superimposable properties, supporting the concept that their activity is also due to the LLV they release in large quantities. However, in later stages of infection, the spleens of Friend leukemia complex-infected mice also contained non-B-suppressing cells possibly derived from the proliferation of nonlymphoid LLV-producing cells caused by the neoplastic process.", "contents": "Suppression of in vitro antibody response by spleen cells of mice infected with Friend-associated lymphatic leukemia virus. The ability of spleen cells of mice infected with oncornaviruses to depress the in vitro antibody responsiveness of normal lymphoid cells was exploited in an attempt to clarify the role played by the lymphatic leukemia virus (LLV) component in the immunodepressive properties of the Friend leukemia complex. Spleen cells of mice infected with LLV or, for comparison, with the entire complex were added to cultures of sheep erythrocyte-primed uninfected spleen cells, and the antibody-forming cells produced by the latter, after antigen restimulation, were assayed. The addition within 2 days from culture initiation of low numbers of cells infected with either virus preparation suppressed all stages of the response affecting the production of both immunoglobulin M and immunoglobulin G antibody. The activity of infected cells resisted doses of ultraviolet radiation which inhibit cell multiplication but was abolished by disrupting the cells and was prevented by the presence of anti-LLV antibodies. The LLV-infected spleen cells responsible for suppression were not removed by treatments which selectively remove or kill macrophages and exhibited surface properties of B lymphocytes. These results were interpreted as indicating that the effect is due to virus (or viral products) released by B cells. The suppressing cells in the spleens of mice in the early days of Friend leukemia complex infection presented superimposable properties, supporting the concept that their activity is also due to the LLV they release in large quantities. However, in later stages of infection, the spleens of Friend leukemia complex-infected mice also contained non-B-suppressing cells possibly derived from the proliferation of nonlymphoid LLV-producing cells caused by the neoplastic process."}
{"id": "PMID:222678", "title": "Development of antibodies reactive in antibody-dependent cellular cytotoxicity in infectious mononucleosis.", "content": "Serial sera from patients with infectious mononucleosis were examined for the emergence of antibodies reactive in antibody-dependent cellular cytotoxicity tests, using Epstein-Barr virus-superinfected Raji cells as targets. For this specific purpose, the antibody-dependent cellular cytotoxicity test proved to be of limited sensitivity because only relatively high serum dilutions can be tested dependably, due to prozone effects at low serum concentrations, and because antibody-dependent cellular cytotoxicity reactions at the 5% level are not always statistically significant. Under the conditions of the test, antibody-dependent cellular cytotoxicity-reactive antibodies were not measurable, or only barely measurable, in early-acute-phase sera, but they became detectable during convalescence and increased thereafter, gradually over many months to the range of titers seen in healthy persons after long-past-primary Epstein-Barr virus infections. The percentages of antibody-dependent cellular cytotoxicity ultimately attained were on the order of 20% in most patients and healthy individuals, but in others did not exceed 10%. The likely identity of the antibodies reactive in the test with antibodies to late Epstein-Barr virus-determined cell membrane antigens has been discussed.", "contents": "Development of antibodies reactive in antibody-dependent cellular cytotoxicity in infectious mononucleosis. Serial sera from patients with infectious mononucleosis were examined for the emergence of antibodies reactive in antibody-dependent cellular cytotoxicity tests, using Epstein-Barr virus-superinfected Raji cells as targets. For this specific purpose, the antibody-dependent cellular cytotoxicity test proved to be of limited sensitivity because only relatively high serum dilutions can be tested dependably, due to prozone effects at low serum concentrations, and because antibody-dependent cellular cytotoxicity reactions at the 5% level are not always statistically significant. Under the conditions of the test, antibody-dependent cellular cytotoxicity-reactive antibodies were not measurable, or only barely measurable, in early-acute-phase sera, but they became detectable during convalescence and increased thereafter, gradually over many months to the range of titers seen in healthy persons after long-past-primary Epstein-Barr virus infections. The percentages of antibody-dependent cellular cytotoxicity ultimately attained were on the order of 20% in most patients and healthy individuals, but in others did not exceed 10%. The likely identity of the antibodies reactive in the test with antibodies to late Epstein-Barr virus-determined cell membrane antigens has been discussed."}
{"id": "PMID:222679", "title": "Interaction of inflammatory cells and oral microorganisms. VIII. Detection of leukotoxic activity of a plaque-derived gram-negative microorganism.", "content": "In the present study we identified a gram-negative anaerobic rod referred to as Y4 which was cytotoxic for human polymorphonuclear leukocytes. Y4 was isolated from dental plaque of a patient with juvenile periodontitis and presented most of the taxonomic characteristics of Actinobacillus species. Under experimental conditions, viable Y4 were cytotoxic for human peripheral blood polymorphonuclear leukocytes in serum-free cultures. Cytotoxicity was dependent on bacterial concentrations and was enhanced in the presence of a fresh or heat-inactivated (56 degrees C, 30 min) autologous serum. Leukotoxicity was independent of phagocytosis. Y4 leukotoxic effect was abolished when bacteria were heat treated (56 degrees C, 30 min) or when incubations were carried out at 4 degrees C instead of at 37 degrees C. The leukotoxicity was monitored by electron microscopy and biochemically by measuring lactate dehydrogenase indicator of cell viability. No cytotoxic effects of Y4 on human mononuclear cells, chicken fibroblasts, or mouse macrophages were detected under the conditions studied. Polymorphonuclear leukocytes may play an important role in the host defense against bacteria in periodontal disease. The cytotoxic effect of Y4 for polymorphonuclear leukocytes presented in this study is the first report of a direct offensive microbial vector in a plaque-derived microorganism and may prove to be relevant in the pathogenesis of juvenile periodontitis.", "contents": "Interaction of inflammatory cells and oral microorganisms. VIII. Detection of leukotoxic activity of a plaque-derived gram-negative microorganism. In the present study we identified a gram-negative anaerobic rod referred to as Y4 which was cytotoxic for human polymorphonuclear leukocytes. Y4 was isolated from dental plaque of a patient with juvenile periodontitis and presented most of the taxonomic characteristics of Actinobacillus species. Under experimental conditions, viable Y4 were cytotoxic for human peripheral blood polymorphonuclear leukocytes in serum-free cultures. Cytotoxicity was dependent on bacterial concentrations and was enhanced in the presence of a fresh or heat-inactivated (56 degrees C, 30 min) autologous serum. Leukotoxicity was independent of phagocytosis. Y4 leukotoxic effect was abolished when bacteria were heat treated (56 degrees C, 30 min) or when incubations were carried out at 4 degrees C instead of at 37 degrees C. The leukotoxicity was monitored by electron microscopy and biochemically by measuring lactate dehydrogenase indicator of cell viability. No cytotoxic effects of Y4 on human mononuclear cells, chicken fibroblasts, or mouse macrophages were detected under the conditions studied. Polymorphonuclear leukocytes may play an important role in the host defense against bacteria in periodontal disease. The cytotoxic effect of Y4 for polymorphonuclear leukocytes presented in this study is the first report of a direct offensive microbial vector in a plaque-derived microorganism and may prove to be relevant in the pathogenesis of juvenile periodontitis."}
{"id": "PMID:222680", "title": "Ultrastructural-immunohistochemical evidence for a maturation defect of temperature-sensitive G31 vesicular stomatitis virus in murine spinal cord neurons.", "content": "Ultrastructural immunoperoxidase studies were done in spinal cords of mice infected with wild type vesicular stomatitis virus or its temperature-sensitive (ts) mutant G31. Infected neurons showed subplasmalemmal staining of viral antigen and staining of viral particles budding from the neuronal membrane in wild-type vesicular stomatitis virus infection, whereas diffuse membrane and cytoplasmic staining with no budding virus was observed in ts G31 infection. Such findings suggest rapid viral assembly and release of viral particles from cells infected with wild-type virus. In contrast, maturation of ts G31 appears defective, and this would lead to accumulation of viral antigen in the cytoplasm of infected cells. These results correlate with studies in neuroblastoma cells which investigated the growth cycles of wild type, ts G31, and the spinal cord isolate of ts G31 as well as the viral protein-synthetic capacity of these viruses.", "contents": "Ultrastructural-immunohistochemical evidence for a maturation defect of temperature-sensitive G31 vesicular stomatitis virus in murine spinal cord neurons. Ultrastructural immunoperoxidase studies were done in spinal cords of mice infected with wild type vesicular stomatitis virus or its temperature-sensitive (ts) mutant G31. Infected neurons showed subplasmalemmal staining of viral antigen and staining of viral particles budding from the neuronal membrane in wild-type vesicular stomatitis virus infection, whereas diffuse membrane and cytoplasmic staining with no budding virus was observed in ts G31 infection. Such findings suggest rapid viral assembly and release of viral particles from cells infected with wild-type virus. In contrast, maturation of ts G31 appears defective, and this would lead to accumulation of viral antigen in the cytoplasm of infected cells. These results correlate with studies in neuroblastoma cells which investigated the growth cycles of wild type, ts G31, and the spinal cord isolate of ts G31 as well as the viral protein-synthetic capacity of these viruses."}
{"id": "PMID:222681", "title": "Endogenous RD-114 virus of cats: absence of antibodies to RD-114 envelope antigens in cats naturally exposed to feline leukemia virus.", "content": "Healthy cats, including those exposed to feline leukemia virus in leukemia cluster households, lack evidence of humoral immunity to virion surface antigens of the endogenous RD-114 virus.", "contents": "Endogenous RD-114 virus of cats: absence of antibodies to RD-114 envelope antigens in cats naturally exposed to feline leukemia virus. Healthy cats, including those exposed to feline leukemia virus in leukemia cluster households, lack evidence of humoral immunity to virion surface antigens of the endogenous RD-114 virus."}
{"id": "PMID:222682", "title": "Inhibition of adenosine 3',5'-monophosphate-dependent protein kinase by staphylococcal alpha-toxin.", "content": "Staphylococcal alpha-toxin inhibited the activity of cyclic adenosine 3',5'-monophosphate-dependent protein kinase by competitive inhibition, probably by its interaction with a cyclic adenosine 3',5'-monophosphate-binding site in the protein kinase molecule.", "contents": "Inhibition of adenosine 3',5'-monophosphate-dependent protein kinase by staphylococcal alpha-toxin. Staphylococcal alpha-toxin inhibited the activity of cyclic adenosine 3',5'-monophosphate-dependent protein kinase by competitive inhibition, probably by its interaction with a cyclic adenosine 3',5'-monophosphate-binding site in the protein kinase molecule."}
{"id": "PMID:222683", "title": "Experimental reproduction of neonatal diarrhea in young gnotobiotic hares simultaneously associated with Clostridium difficile and other Clostridium strains.", "content": "Clostridium difficile, C. perfringens, and C. tertium are very often present simultaneously in the feces of conventional diarrheic young hares, whereas these three bacterial species are rarely encountered and never present simultaneously in the feces of healthy young hares. When a strain of each of the three bacterial species was monoassociated with axenic young hares, the appearance of pathological disorders was only observed in animals monoassociated with C. difficile, when the number of C. difficile exceeded 10(8) per g of fresh feces. When a strain of C. perfringens or a strain of C. tertium, or both, was associated with C. difficile, diarrhea and death occurred more rapidly than in hares monoassociated with C. difficile. C. difficile and C. perfringens became established more rapidly when disassociated than when monoassociated with axenic hares. The association of C. perfringens and C. tertium with axenic hares did not bring about any pathological disorders. It may be concluded that C. difficile is the causal agent of neonatal diarrhea in conventional and gnotobiotic young hares and that other strains of Clostridium enhance its pathogenic effect. C difficile alone or associated with C. perfringens or C. tertium does not play any pathogenic role in young rats, mice, or rabbits.", "contents": "Experimental reproduction of neonatal diarrhea in young gnotobiotic hares simultaneously associated with Clostridium difficile and other Clostridium strains. Clostridium difficile, C. perfringens, and C. tertium are very often present simultaneously in the feces of conventional diarrheic young hares, whereas these three bacterial species are rarely encountered and never present simultaneously in the feces of healthy young hares. When a strain of each of the three bacterial species was monoassociated with axenic young hares, the appearance of pathological disorders was only observed in animals monoassociated with C. difficile, when the number of C. difficile exceeded 10(8) per g of fresh feces. When a strain of C. perfringens or a strain of C. tertium, or both, was associated with C. difficile, diarrhea and death occurred more rapidly than in hares monoassociated with C. difficile. C. difficile and C. perfringens became established more rapidly when disassociated than when monoassociated with axenic hares. The association of C. perfringens and C. tertium with axenic hares did not bring about any pathological disorders. It may be concluded that C. difficile is the causal agent of neonatal diarrhea in conventional and gnotobiotic young hares and that other strains of Clostridium enhance its pathogenic effect. C difficile alone or associated with C. perfringens or C. tertium does not play any pathogenic role in young rats, mice, or rabbits."}
{"id": "PMID:222684", "title": "Evaluation of a ribosomal vaccine against pertussis.", "content": "A crude ribosomal vaccine derived from Bordetella pertussis administered to ICR and N:NIH (SW) strains of mice protected them effectively against a standardized intracranial challenge. The dose of vaccine that protected half the mice was less for N:NIH (SW) than for ICR mice and compared favorably with a killed reference vaccine. Ribosomes prepared from bacteria ground with washed sea sand were more immunogenic than those obtained by rupture with alumina or with a Braun homogenizer. The protective effect of the crude ribosomes was not an innate part of the organelle but was due to a substance or substances that could be removed from them by a 1 M NH4Cl wash. The material in the wash was highly immunogenic and retained both the histamine-sensitizing and leukocytosis-promoting properties. It lost much of the dermonecrotic activity and was poorly pyrogenic in rabbits. The most potent pyrogen was present in the washed ribosomes, which apparently, retained the endotoxic components of the cell wall. The best vaccines permitted acceptable weight gain in the immunized mice.", "contents": "Evaluation of a ribosomal vaccine against pertussis. A crude ribosomal vaccine derived from Bordetella pertussis administered to ICR and N:NIH (SW) strains of mice protected them effectively against a standardized intracranial challenge. The dose of vaccine that protected half the mice was less for N:NIH (SW) than for ICR mice and compared favorably with a killed reference vaccine. Ribosomes prepared from bacteria ground with washed sea sand were more immunogenic than those obtained by rupture with alumina or with a Braun homogenizer. The protective effect of the crude ribosomes was not an innate part of the organelle but was due to a substance or substances that could be removed from them by a 1 M NH4Cl wash. The material in the wash was highly immunogenic and retained both the histamine-sensitizing and leukocytosis-promoting properties. It lost much of the dermonecrotic activity and was poorly pyrogenic in rabbits. The most potent pyrogen was present in the washed ribosomes, which apparently, retained the endotoxic components of the cell wall. The best vaccines permitted acceptable weight gain in the immunized mice."}
{"id": "PMID:222685", "title": "Assays for endogenous and exogenous lymphoid leukosis viruses and chick helper factor with RSV(--) cell lines.", "content": "Japanese quail cells transformed by the envelope-defective Bryan high-titer strain of Rous sarcoma virus [R(-)Q] were used as a source of the Rous sarcoma virus genome in three kinds of assays. (i) The simplest and most sensitive assay for infectious, endogenous viruses of the chicken belonging to subgroup E involved infection of a mixture of R(-)Q cells and turkey cells with the sample and assay of supernatants of these cells for focus formation on subgroup E susceptible cells. (ii) Inactivated Sendai virus-induced fusion of R(-)Q cells with live test cells was found to be a specific method for detection of chick helper factor. Focus formation by supernatant of the fused cells on subgroup E susceptible cells was correlated with the presence of subgroup E envelope glycoprotein on the plasma membranes of test cells. Whole blood cells as well as fibroblasts could be used in this assay. (iii) A method of assay for exogenous lymphoid leukosis viruses in which mixed cultures of R(-)Q cells and C/E cells and assay of supernatants for focus formation on C/E cells was as sensitive as assays presently used for exogenous lymphoid leukosis virus. Because no infectious Rous sarcoma virus was used as part of the procedure, the assays for infectious virus described here yielded pure pseudotypes of the input virus, an advantage for determining purity and subgroup of the input virus.", "contents": "Assays for endogenous and exogenous lymphoid leukosis viruses and chick helper factor with RSV(--) cell lines. Japanese quail cells transformed by the envelope-defective Bryan high-titer strain of Rous sarcoma virus [R(-)Q] were used as a source of the Rous sarcoma virus genome in three kinds of assays. (i) The simplest and most sensitive assay for infectious, endogenous viruses of the chicken belonging to subgroup E involved infection of a mixture of R(-)Q cells and turkey cells with the sample and assay of supernatants of these cells for focus formation on subgroup E susceptible cells. (ii) Inactivated Sendai virus-induced fusion of R(-)Q cells with live test cells was found to be a specific method for detection of chick helper factor. Focus formation by supernatant of the fused cells on subgroup E susceptible cells was correlated with the presence of subgroup E envelope glycoprotein on the plasma membranes of test cells. Whole blood cells as well as fibroblasts could be used in this assay. (iii) A method of assay for exogenous lymphoid leukosis viruses in which mixed cultures of R(-)Q cells and C/E cells and assay of supernatants for focus formation on C/E cells was as sensitive as assays presently used for exogenous lymphoid leukosis virus. Because no infectious Rous sarcoma virus was used as part of the procedure, the assays for infectious virus described here yielded pure pseudotypes of the input virus, an advantage for determining purity and subgroup of the input virus."}
{"id": "PMID:222686", "title": "Effect of cyclic adenosine 3',5'-monophosphate antagonists on endotoxin-induced inhibition of human neutrophil chemotaxis.", "content": "We reported previously that Escherichia coli endotoxin inhibited human neutrophil chemotaxis toward C5a. This effect of endotoxin was antagonized by anti-inflammatory steroids. We now report that dibutyryl cyclic adenosine 3',5'-monophosphate, prostaglandin E1, isoproterenol, and cholera toxin also antagonize the suppression of chemotaxis by endotoxin. Each compound inhibited the effect of endotoxin in a dose-dependent fashion. To be effective, each compound except cholera toxin had to be present at the time of endotoxin challenge. Furthermore, propranolol blocked the protective effect of isoproterenol against endotoxin but not the protective effect of dibutyrl cyclic adenosine 3',5'-monophosphate or prostaglandin E1. Dibutyryl cyclic guanosine 3',5'-monophosphate, adenosine 5'-monophosphate, phenylephrine, prostaglandin F2 alpha, and carbachol did not modify the suppression of chemotaxis by endotoxin. Anti-inflammatory steroids and dibutyryl cyclic adenosine 3',5'-monophosphate are thought to stabilize phospholipids in certain cell membranes. This phospholipid-stabilizing action may contribute, at least in part, to the protective effect against endotoxin-mediated suppression of neutrophil chemotaxis.", "contents": "Effect of cyclic adenosine 3',5'-monophosphate antagonists on endotoxin-induced inhibition of human neutrophil chemotaxis. We reported previously that Escherichia coli endotoxin inhibited human neutrophil chemotaxis toward C5a. This effect of endotoxin was antagonized by anti-inflammatory steroids. We now report that dibutyryl cyclic adenosine 3',5'-monophosphate, prostaglandin E1, isoproterenol, and cholera toxin also antagonize the suppression of chemotaxis by endotoxin. Each compound inhibited the effect of endotoxin in a dose-dependent fashion. To be effective, each compound except cholera toxin had to be present at the time of endotoxin challenge. Furthermore, propranolol blocked the protective effect of isoproterenol against endotoxin but not the protective effect of dibutyrl cyclic adenosine 3',5'-monophosphate or prostaglandin E1. Dibutyryl cyclic guanosine 3',5'-monophosphate, adenosine 5'-monophosphate, phenylephrine, prostaglandin F2 alpha, and carbachol did not modify the suppression of chemotaxis by endotoxin. Anti-inflammatory steroids and dibutyryl cyclic adenosine 3',5'-monophosphate are thought to stabilize phospholipids in certain cell membranes. This phospholipid-stabilizing action may contribute, at least in part, to the protective effect against endotoxin-mediated suppression of neutrophil chemotaxis."}
{"id": "PMID:222687", "title": "New strain of mouse hepatitis virus as the cause of lethal enteritis in infant mice.", "content": "A new strain of mouse hepatitis virus (MHV) was isolated from pooled gut suspensions from an epizootic of lethal enteritis in newborn mice. Negative-contrast electron microscopy showed an abundance of coronavirus particles in the intestinal contents and intestinal epithelium of moribund mice. We found no other virus in the epizootic. Dams seroconverted to MHV polyvalent antigen and to the agent isolated, but did not develop antibodies to other known mouse pathogens. Virus propagated in NCTC-1469 tissue culture produced enteric disease in suckling mice but not fatal diarrhea; the dams of these mice also developed antibodies to MHV and to the isolates. By complement fixation, single radial hemolysis, and quantal neutralization tests, we found the isolates antigenically most closely related to MHV-S, unilaterally related to MHV-JHM, and more distantly related to MHV-1, MHV-3, MHV-A59, and human coronavirus OC-43. We also studied cross-reactions among the murine and human coronaviruses in detail. Tissues of infected newborn mice were examined by light microscopy, thin-section electron microscopy, and frozen-section indirect immunofluorescence, revealing that viral antigen, virus particles, and pathological changes were limited to the intestinal tract. We have designated our isolates as MHV-S/CDC.", "contents": "New strain of mouse hepatitis virus as the cause of lethal enteritis in infant mice. A new strain of mouse hepatitis virus (MHV) was isolated from pooled gut suspensions from an epizootic of lethal enteritis in newborn mice. Negative-contrast electron microscopy showed an abundance of coronavirus particles in the intestinal contents and intestinal epithelium of moribund mice. We found no other virus in the epizootic. Dams seroconverted to MHV polyvalent antigen and to the agent isolated, but did not develop antibodies to other known mouse pathogens. Virus propagated in NCTC-1469 tissue culture produced enteric disease in suckling mice but not fatal diarrhea; the dams of these mice also developed antibodies to MHV and to the isolates. By complement fixation, single radial hemolysis, and quantal neutralization tests, we found the isolates antigenically most closely related to MHV-S, unilaterally related to MHV-JHM, and more distantly related to MHV-1, MHV-3, MHV-A59, and human coronavirus OC-43. We also studied cross-reactions among the murine and human coronaviruses in detail. Tissues of infected newborn mice were examined by light microscopy, thin-section electron microscopy, and frozen-section indirect immunofluorescence, revealing that viral antigen, virus particles, and pathological changes were limited to the intestinal tract. We have designated our isolates as MHV-S/CDC."}
{"id": "PMID:222688", "title": "Persistent infection of a human lymphoblastoid cell line with equine herpesvirus 1.", "content": "Infection of a human lymphoblastoid cell line (Jijoye line derived from a Burkitt lymphoma which contains Epstein-Barr virus) with equine herpesvirus 1, maintained and observed for 53 days, was characterized by the continuous production of infectious extracellular and intracellular virus. Maximum virus production correlated with active cell multiplication. Less than 15% of the cells possessed viral capsid antigen at any one time. Five percent of the cells in the Jijoye line possess Epstein-Barr viral capsid antigen; 80% of the Epstein-Barr viral caspid-containing cells also contained equine herpesvirus 1 antigen as detected by double staining. The interaction of equine herpesvirus 1 and lymphoblastoid cells provides a useful in vitro model which may help clarify the mechanism for herpesvirus latency.", "contents": "Persistent infection of a human lymphoblastoid cell line with equine herpesvirus 1. Infection of a human lymphoblastoid cell line (Jijoye line derived from a Burkitt lymphoma which contains Epstein-Barr virus) with equine herpesvirus 1, maintained and observed for 53 days, was characterized by the continuous production of infectious extracellular and intracellular virus. Maximum virus production correlated with active cell multiplication. Less than 15% of the cells possessed viral capsid antigen at any one time. Five percent of the cells in the Jijoye line possess Epstein-Barr viral capsid antigen; 80% of the Epstein-Barr viral caspid-containing cells also contained equine herpesvirus 1 antigen as detected by double staining. The interaction of equine herpesvirus 1 and lymphoblastoid cells provides a useful in vitro model which may help clarify the mechanism for herpesvirus latency."}
{"id": "PMID:222689", "title": "Effects of viral pneumonia on lung macrophage lysosomal enzymes.", "content": "During viral pneumonitis in mice, lung fluid protein and free lysosomal enzyme activity are increased while macrophage lysosomal enzymes are decreased.", "contents": "Effects of viral pneumonia on lung macrophage lysosomal enzymes. During viral pneumonitis in mice, lung fluid protein and free lysosomal enzyme activity are increased while macrophage lysosomal enzymes are decreased."}
{"id": "PMID:222690", "title": "Long-term C-cell-mediated immunity to Epstein-Barr virus in man. II. Components necessary for regression in virus-infected leukocyte cultures.", "content": "Regression of EB-virus-induced transformation occurs exclusively in cultures of leukocytes from seropositive donors. Studies have shown that the strength of regression could be assayed in terms of the proportion of T cells which must be added to the autologous EB virus-infected T-cell-depleted population in order to establish regression in the culture. The in vitro regression phenomenon was strongly T-cell-dependent but did not require the presence of either monocytes or, as a potential antigenic stimulus, the residual viral envelope material on the surface of virus-infected B cells. The T-cell-depleted population from seropositive donors sometimes transformed (7/60 cultures) without the experimental addition of virus. Regression appeared to be independent of cytotoxic mechanisms involving anti-viral antibodies and not to be mediated by soluble factors released into culture medium.", "contents": "Long-term C-cell-mediated immunity to Epstein-Barr virus in man. II. Components necessary for regression in virus-infected leukocyte cultures. Regression of EB-virus-induced transformation occurs exclusively in cultures of leukocytes from seropositive donors. Studies have shown that the strength of regression could be assayed in terms of the proportion of T cells which must be added to the autologous EB virus-infected T-cell-depleted population in order to establish regression in the culture. The in vitro regression phenomenon was strongly T-cell-dependent but did not require the presence of either monocytes or, as a potential antigenic stimulus, the residual viral envelope material on the surface of virus-infected B cells. The T-cell-depleted population from seropositive donors sometimes transformed (7/60 cultures) without the experimental addition of virus. Regression appeared to be independent of cytotoxic mechanisms involving anti-viral antibodies and not to be mediated by soluble factors released into culture medium."}
{"id": "PMID:222691", "title": "Long-term T-cell-mediated immunity to Epstein-Barr virus in man. III. Activation of cytotoxic T cells in virus-infected leukocyte cultures.", "content": "Experiments have been conducted to determine the role played by immune T cells in the regression of EB-virus-induced transformation which is exclusively seen in leukocyte cultures from sero-positive donors. Kinetic studies suggest that, in virus-infected cultures from such donors, a population of T cells proliferates within the first 2 weeks apparently in response to the appearance of virus-infected B cells. This proliferation continues to some extent during the period of regression. Nonspecific induction of T-cell proliferation by PHA did not induce regression in virus-infected cultures from seronegative donors and acutally prevented the regression in seropositive donor cultures. T cells harvested from seropositive donor cultures 11-14 days post infection were generally much more inhibitory to the growth of the autologous EB-virus-transformed cell line than were T cells either freshly prepared from whole blood or harvested from corresponding uninfected cultures; this inhibitory activity was either absent or much diminished when assayed against allogeneic target cell lines. The results suggest that virus-specific memory T cells capable of mounting a cytotoxic response when properly challenged in vitro.", "contents": "Long-term T-cell-mediated immunity to Epstein-Barr virus in man. III. Activation of cytotoxic T cells in virus-infected leukocyte cultures. Experiments have been conducted to determine the role played by immune T cells in the regression of EB-virus-induced transformation which is exclusively seen in leukocyte cultures from sero-positive donors. Kinetic studies suggest that, in virus-infected cultures from such donors, a population of T cells proliferates within the first 2 weeks apparently in response to the appearance of virus-infected B cells. This proliferation continues to some extent during the period of regression. Nonspecific induction of T-cell proliferation by PHA did not induce regression in virus-infected cultures from seronegative donors and acutally prevented the regression in seropositive donor cultures. T cells harvested from seropositive donor cultures 11-14 days post infection were generally much more inhibitory to the growth of the autologous EB-virus-transformed cell line than were T cells either freshly prepared from whole blood or harvested from corresponding uninfected cultures; this inhibitory activity was either absent or much diminished when assayed against allogeneic target cell lines. The results suggest that virus-specific memory T cells capable of mounting a cytotoxic response when properly challenged in vitro."}
{"id": "PMID:222692", "title": "The role of the macrophages in Marek's disease: in vitro and in vivo studies.", "content": "Macrophages form S- and K-strain Leghorn chickens, susceptible and restant to Marek's disease (MD) respectively, were studied to determine the macrophage contribution to the dynamics of MD infection, tumorigenesis and genetic resistance to this disease. In vitro studies demonstrated that macrophages from bothstrains were similar in their responses toward JM strain of Marek's disease virus (MDV) and JM-1 tumor cells. Macrophages were observed to phagocytize JM virus, but the interiorized virus was not seen to replicate within the macrophage or induce antigenic changes of the cell membrane. Clearance of JM-1 tumor cells was by both cytolytic and phagocytic mechanism. In vivo selective suppression of macrophage functions by antimacrophage serum or trypan blue inoculations resulted in significantly elevated viral titers and increased tumorigenesis, as compared to infected, non-suppressed or non-infected control groups. Results from this study indicate that genetic susceptibility or resistance to MD, as exhibited by S- and K-strain chickens, respectively, is not controlled at the macrophage level. The role of the macrophage in MD infection appears to be specifically surveillance.", "contents": "The role of the macrophages in Marek's disease: in vitro and in vivo studies. Macrophages form S- and K-strain Leghorn chickens, susceptible and restant to Marek's disease (MD) respectively, were studied to determine the macrophage contribution to the dynamics of MD infection, tumorigenesis and genetic resistance to this disease. In vitro studies demonstrated that macrophages from bothstrains were similar in their responses toward JM strain of Marek's disease virus (MDV) and JM-1 tumor cells. Macrophages were observed to phagocytize JM virus, but the interiorized virus was not seen to replicate within the macrophage or induce antigenic changes of the cell membrane. Clearance of JM-1 tumor cells was by both cytolytic and phagocytic mechanism. In vivo selective suppression of macrophage functions by antimacrophage serum or trypan blue inoculations resulted in significantly elevated viral titers and increased tumorigenesis, as compared to infected, non-suppressed or non-infected control groups. Results from this study indicate that genetic susceptibility or resistance to MD, as exhibited by S- and K-strain chickens, respectively, is not controlled at the macrophage level. The role of the macrophage in MD infection appears to be specifically surveillance."}
{"id": "PMID:222693", "title": "Enhancement of host cell reactivation of ultraviolet-irradiated Herpes simplex virus by caffeine, hydroxyurea and 5-bromodeoxyuridine.", "content": "Enhancement of host cell reactivation (HCR) of ultraviolet (UV)-irradiated herpes simplex virus (HSV) was demonstrated in cell cultures pretreated with caffeine, hydroxyurea, or 5-bromodeoxyuridine (BrdUrd). The effect of caffeine on HCR was shown to depend on the time of drug treatment with respect to infection. In cultures treated with caffeine during the course of virus replication, the infectivity of irradiated HSV was reduced about nine-fold, while cultures pretreated with the drug before infection showed an increase in infectivity. The extent of HCR enhancement depended on the time interval between treatment with caffeine and infection, drug concentration, and the UV irradiation dose to which HSV was exposed. Magnitude of enhancement of HCR by caffeine differed in various cell species. The results suggest that enhanced HCR of UV-irradiated HSV by DNA antimetabolities is associated with DNA repair activated in consequence of cell DNA damage.", "contents": "Enhancement of host cell reactivation of ultraviolet-irradiated Herpes simplex virus by caffeine, hydroxyurea and 5-bromodeoxyuridine. Enhancement of host cell reactivation (HCR) of ultraviolet (UV)-irradiated herpes simplex virus (HSV) was demonstrated in cell cultures pretreated with caffeine, hydroxyurea, or 5-bromodeoxyuridine (BrdUrd). The effect of caffeine on HCR was shown to depend on the time of drug treatment with respect to infection. In cultures treated with caffeine during the course of virus replication, the infectivity of irradiated HSV was reduced about nine-fold, while cultures pretreated with the drug before infection showed an increase in infectivity. The extent of HCR enhancement depended on the time interval between treatment with caffeine and infection, drug concentration, and the UV irradiation dose to which HSV was exposed. Magnitude of enhancement of HCR by caffeine differed in various cell species. The results suggest that enhanced HCR of UV-irradiated HSV by DNA antimetabolities is associated with DNA repair activated in consequence of cell DNA damage."}
{"id": "PMID:222694", "title": "Lymphomas resembling lymphoid leukosis in chickens inoculated with reticuloendotheliosis virus.", "content": "Chickens inoculated as embyros or at hatching with the chick syncytial strain of reticuloendotheliosis virus developed a high incidence of lymphoid neoplasms between the 17th and 43rd weeks of age, involving principally the liver and bursa of Fabricius. On the basis of organ distribution, latent period, pathology and surface IgM production, the lymphomas closely resembled those of lymphoid leukosis. One inoculated chicken developed a myxosarcoma. No tumors were observed in uninoculated controls. The tumor-bearing chickens were free of infection with Marek's disease virus and exogenous avian leukosis virus (ALV) of subgroups A, B, C or D. However, the chickens were known to express endogenous ALV genes to varying degrees.", "contents": "Lymphomas resembling lymphoid leukosis in chickens inoculated with reticuloendotheliosis virus. Chickens inoculated as embyros or at hatching with the chick syncytial strain of reticuloendotheliosis virus developed a high incidence of lymphoid neoplasms between the 17th and 43rd weeks of age, involving principally the liver and bursa of Fabricius. On the basis of organ distribution, latent period, pathology and surface IgM production, the lymphomas closely resembled those of lymphoid leukosis. One inoculated chicken developed a myxosarcoma. No tumors were observed in uninoculated controls. The tumor-bearing chickens were free of infection with Marek's disease virus and exogenous avian leukosis virus (ALV) of subgroups A, B, C or D. However, the chickens were known to express endogenous ALV genes to varying degrees."}
{"id": "PMID:222695", "title": "Idiopathic mammary tumors in BALB/c mice.", "content": "A colony of BALB/c mice consisting of two sublines with a high incidence of mammary tumors was examined for the presence of a mammary tumor virus (MuMTV). The mammary tumor incidences in the two sublines were 18% and 35% at average tumor age 19-20 months. Over a period of 8 years, their milk at third to tenth lactations were monitored for the presence of MuMTV antigen,and the milk and tumors were examined for the presence of B particles. Neither antigen nor B particles were found. Milk and tumor extracts from the higher mammary tumor lines were also assayed for MuMTV bioactivity by intraperitoneal inoculation of weanling C57BL, BALB/c, and RIIIf females. No response was obtained, except possible in RIIIf. Both the MuMTV antigen incidence and the tumor incidence in inoculated RIIIf mice were somewhat elevated over controls. The question remains unanswered as to whether there is an active MuMTV in our colony of tumor-bearing BALB/c mice and, if there is, whether it is associated with B particles.", "contents": "Idiopathic mammary tumors in BALB/c mice. A colony of BALB/c mice consisting of two sublines with a high incidence of mammary tumors was examined for the presence of a mammary tumor virus (MuMTV). The mammary tumor incidences in the two sublines were 18% and 35% at average tumor age 19-20 months. Over a period of 8 years, their milk at third to tenth lactations were monitored for the presence of MuMTV antigen,and the milk and tumors were examined for the presence of B particles. Neither antigen nor B particles were found. Milk and tumor extracts from the higher mammary tumor lines were also assayed for MuMTV bioactivity by intraperitoneal inoculation of weanling C57BL, BALB/c, and RIIIf females. No response was obtained, except possible in RIIIf. Both the MuMTV antigen incidence and the tumor incidence in inoculated RIIIf mice were somewhat elevated over controls. The question remains unanswered as to whether there is an active MuMTV in our colony of tumor-bearing BALB/c mice and, if there is, whether it is associated with B particles."}
{"id": "PMID:222700", "title": "Antibodies against haptens in the study of structure and biological activity of growth hormone.", "content": "The alpha-amino group of bovine Growth Hormone was selectively modified with TNBS with no detectable changes in growth promoting activity. TNP was used as hapten for the production of antibodies against the end terminal region of bGH. The region near the alpha-amino group is not involved in the binding of bGH to rat liver cells, and it seems to be away from the part of the molecule that interacts with the cell binding sites.", "contents": "Antibodies against haptens in the study of structure and biological activity of growth hormone. The alpha-amino group of bovine Growth Hormone was selectively modified with TNBS with no detectable changes in growth promoting activity. TNP was used as hapten for the production of antibodies against the end terminal region of bGH. The region near the alpha-amino group is not involved in the binding of bGH to rat liver cells, and it seems to be away from the part of the molecule that interacts with the cell binding sites."}
{"id": "PMID:222701", "title": "Studies on pituitary follitropin. V. Isolation of the subunits of the human hormone and reaction of the amino groups with acylating agents.", "content": "The alpha and beta subunits of human follitropin were isolated in a high state of purity. The tryptophan fluorescence of the native hormone and the isolated beta subunit are different. The N-terminus of the alpha and beta subunits was identified as valine and aspartic acid respectively. While recombination of the isolated alpha and beta subunits restores the electrophoretic mobility of the intact hormone, its receptor binding activity cannot be fully regenerated. Substitution of the human follitropin alpha by an ovine lutropin alpha subunit, to form a recombinant with the follitropin beta subunit, generates a complex with 2-3 receptor binding activity of the native human follitropin and the same activity as ovine follitropin. Acylation of the intact hormone does not disrupt the quaternary structure but leads to complete inactivation. Acylation studies with the subunits suggests the crucial role of the epsilon-amino groups of the alpha subunit in determining biological activity.", "contents": "Studies on pituitary follitropin. V. Isolation of the subunits of the human hormone and reaction of the amino groups with acylating agents. The alpha and beta subunits of human follitropin were isolated in a high state of purity. The tryptophan fluorescence of the native hormone and the isolated beta subunit are different. The N-terminus of the alpha and beta subunits was identified as valine and aspartic acid respectively. While recombination of the isolated alpha and beta subunits restores the electrophoretic mobility of the intact hormone, its receptor binding activity cannot be fully regenerated. Substitution of the human follitropin alpha by an ovine lutropin alpha subunit, to form a recombinant with the follitropin beta subunit, generates a complex with 2-3 receptor binding activity of the native human follitropin and the same activity as ovine follitropin. Acylation of the intact hormone does not disrupt the quaternary structure but leads to complete inactivation. Acylation studies with the subunits suggests the crucial role of the epsilon-amino groups of the alpha subunit in determining biological activity."}
{"id": "PMID:222702", "title": "Tumor regrowth after irradiation; an experimental approach.", "content": "Structural changes in irradiated tumors and their regrowth were studied in a rat hepatoma, AH109A, using histological and transparent-chamber techniques. The development of the tumour was examined by means of vascular morphometry as observed in the chamber. Schematically, the tumour tissue was divided into four isocentric layers according to vascular morphology and measurements of vessel volume, surface area, and length per mm3 of tissue. The vascularity was greatest in the outermost region, decreased towards the inner parts and reached an absence of vascularity at the central necrosis. The tumors were gamma- or X-irradiated with various doses. The inside hypoxic region was destroyed completely after 3000 rad, and regrowths started exclusively from the outermost area of the tumour where enhancement of the effect of radiation by oxygen was thought to be greatest. Possible mechanisms of tumour regrowth are discussed.", "contents": "Tumor regrowth after irradiation; an experimental approach. Structural changes in irradiated tumors and their regrowth were studied in a rat hepatoma, AH109A, using histological and transparent-chamber techniques. The development of the tumour was examined by means of vascular morphometry as observed in the chamber. Schematically, the tumour tissue was divided into four isocentric layers according to vascular morphology and measurements of vessel volume, surface area, and length per mm3 of tissue. The vascularity was greatest in the outermost region, decreased towards the inner parts and reached an absence of vascularity at the central necrosis. The tumors were gamma- or X-irradiated with various doses. The inside hypoxic region was destroyed completely after 3000 rad, and regrowths started exclusively from the outermost area of the tumour where enhancement of the effect of radiation by oxygen was thought to be greatest. Possible mechanisms of tumour regrowth are discussed."}
{"id": "PMID:222704", "title": "Ocular surface manifestations of the major viruses.", "content": "The ocular surface is often the first site of involvement by viral infections. Background information, clinical presentations, and current treatment of three major viruses--herpes simplex, varicella-zoster, and adenovirus, have been presented in detail in this chapter. The effects of adenoviruses are usually transient and may be regarded as a nuisance. Infection with herpes simplex or varicella-zoster may lead to prolonged activity of the disease and life-long treatment with occasional loss of useful vision. It is apparent that our understanding of the clinical behavior of the major viruses has increased in recent years. Therapeutic criteria and modalities have also improved for some of the complications of the viruses. Much work needs to be done for some of the other manifestations, i.e., failure of reepithelialization, stromal melting, scarring, vascularization, and inflammation.", "contents": "Ocular surface manifestations of the major viruses. The ocular surface is often the first site of involvement by viral infections. Background information, clinical presentations, and current treatment of three major viruses--herpes simplex, varicella-zoster, and adenovirus, have been presented in detail in this chapter. The effects of adenoviruses are usually transient and may be regarded as a nuisance. Infection with herpes simplex or varicella-zoster may lead to prolonged activity of the disease and life-long treatment with occasional loss of useful vision. It is apparent that our understanding of the clinical behavior of the major viruses has increased in recent years. Therapeutic criteria and modalities have also improved for some of the complications of the viruses. Much work needs to be done for some of the other manifestations, i.e., failure of reepithelialization, stromal melting, scarring, vascularization, and inflammation."}
{"id": "PMID:222706", "title": "Demonstration of a protease inhibitor in the cornea.", "content": "Sequential extraction of bovine corneal homogenates with aqueous 0.154M NaCl, 0.5M NaCl and 3M guanidine HCl revealed the presence, in the two sodium chloride extracts, of trypsin inhibitory factors. Upon gel-filtration chromatography of the o.5M NaCl soluble corneal material on Sephadex G-75, two peaks with trypsin inhibitory activity were resolved. One peak was eluted in the void volume, whereas a second peak had mobility corresponding to a molecular weight fraction much lower than, and therefore distinct from, alpha 1-antitrypsin inhibitor. The possible implication of this inhibitory factor in the pathogenesis of corneal ulceration is briefly discussed.", "contents": "Demonstration of a protease inhibitor in the cornea. Sequential extraction of bovine corneal homogenates with aqueous 0.154M NaCl, 0.5M NaCl and 3M guanidine HCl revealed the presence, in the two sodium chloride extracts, of trypsin inhibitory factors. Upon gel-filtration chromatography of the o.5M NaCl soluble corneal material on Sephadex G-75, two peaks with trypsin inhibitory activity were resolved. One peak was eluted in the void volume, whereas a second peak had mobility corresponding to a molecular weight fraction much lower than, and therefore distinct from, alpha 1-antitrypsin inhibitor. The possible implication of this inhibitory factor in the pathogenesis of corneal ulceration is briefly discussed."}
{"id": "PMID:222707", "title": "Temperature sensitivity of the arenavirus junin isolated from persistently infected Vero cells.", "content": "A persistently infected cell culture was established from Vero cells surviving primary infection with wild-type Junin virus (JVwt). The cells were refractory to superinfection by both Junin virus and the related Tacaribe virus. Replication of virus released from the persistently infected cells (JVpi) was inhibited at 39 degrees. JVpi did not interfere with JVwt at 37 degrees, and it was inactivated at 37, 40, 43, 46 and 50 degrees much more rapidly than was JVwt.", "contents": "Temperature sensitivity of the arenavirus junin isolated from persistently infected Vero cells. A persistently infected cell culture was established from Vero cells surviving primary infection with wild-type Junin virus (JVwt). The cells were refractory to superinfection by both Junin virus and the related Tacaribe virus. Replication of virus released from the persistently infected cells (JVpi) was inhibited at 39 degrees. JVpi did not interfere with JVwt at 37 degrees, and it was inactivated at 37, 40, 43, 46 and 50 degrees much more rapidly than was JVwt."}
{"id": "PMID:222708", "title": "Disulfide bonds in Sendai virus glycoproteins.", "content": "The precursor of fusion protein (Fo) in Sendai virus growth in Vero cells can be cleaved by trypsin to forms F1 and F2, which can be resolved on SDS-polyacrylamide gels. However, if disulfide bonds are preserved during electrophoresis, F1 and F2 remain linked together even after trypsin treatment (F). Sendai virus growth in embryonated chicken eggs does not contain the precursor Fo. However, an F protein was found for Sendai virus grown in eggs when disulfide bonds were preserved during electrophoresis. The hemagglutinin-neuraminidase (HN) glycoproteins also appear to be disulfide-linked to form large complexes which are observed on SDS-polyacrylamide gels of nonreduced samples.", "contents": "Disulfide bonds in Sendai virus glycoproteins. The precursor of fusion protein (Fo) in Sendai virus growth in Vero cells can be cleaved by trypsin to forms F1 and F2, which can be resolved on SDS-polyacrylamide gels. However, if disulfide bonds are preserved during electrophoresis, F1 and F2 remain linked together even after trypsin treatment (F). Sendai virus growth in embryonated chicken eggs does not contain the precursor Fo. However, an F protein was found for Sendai virus grown in eggs when disulfide bonds were preserved during electrophoresis. The hemagglutinin-neuraminidase (HN) glycoproteins also appear to be disulfide-linked to form large complexes which are observed on SDS-polyacrylamide gels of nonreduced samples."}
{"id": "PMID:222709", "title": "In vitro synthesis of infectious DNA copies of the Rous sarcoma virus genome.", "content": "Detergent-disrupted virions of Rous sarcoma virus can synthesize in vitro an infectious viral DNA. Infectivity of the DNA was determined in transfection assays at the endpoint dilution. It was found that the specific infectivity of the crude endogenous reaction product was 34 infectious units/microgram. The endogenous reaction yielded up to 8.5 x 10(-7) infectious units per biologically active input virion, i.e., nearly 0.1 -1 infectious molecules. The possible structure of these molecules is discussed.", "contents": "In vitro synthesis of infectious DNA copies of the Rous sarcoma virus genome. Detergent-disrupted virions of Rous sarcoma virus can synthesize in vitro an infectious viral DNA. Infectivity of the DNA was determined in transfection assays at the endpoint dilution. It was found that the specific infectivity of the crude endogenous reaction product was 34 infectious units/microgram. The endogenous reaction yielded up to 8.5 x 10(-7) infectious units per biologically active input virion, i.e., nearly 0.1 -1 infectious molecules. The possible structure of these molecules is discussed."}
{"id": "PMID:222711", "title": "[Herpesviruses in man].", "content": "The importance and the extent of the inter-actions between herpes viruses and man is beginning to be understood. As more is learned about the natural histories of these viruses, it is becoming apparent that they have in common: Horizontal spread during childhood, often with subclinical infection. Latency in the host for many years, probably for life. Potential for reactivation at a later time. Host immune response maintained for life. Potential for oncogeneiss. A more thorough knowledge of the biochemistry and the biology of these viruses promises to be the foundation of more effective treatment and prevention.", "contents": "[Herpesviruses in man]. The importance and the extent of the inter-actions between herpes viruses and man is beginning to be understood. As more is learned about the natural histories of these viruses, it is becoming apparent that they have in common: Horizontal spread during childhood, often with subclinical infection. Latency in the host for many years, probably for life. Potential for reactivation at a later time. Host immune response maintained for life. Potential for oncogeneiss. A more thorough knowledge of the biochemistry and the biology of these viruses promises to be the foundation of more effective treatment and prevention."}
{"id": "PMID:222713", "title": "Myoclonic encephalopathy of infants or \"dancing eyes syndrome\". Report of 7 cases with long-term follow-up and review of the literature (cases with and without neuroblastoma).", "content": "We describe 7 children with myoclonic encephalopathy of infants (MEI). MEI is a clinical entity characterized by an acute or subacute onset of polymyoclonia, cerebellar ataxia and opsoclonus (\"dancing eyes\"). It occurs either spontaneously, following an infectiuos illness or in association with an occult neuroblastoma. It is likely that immunological factors play a role in the pathogenesis. Steroid therapy resulted in rapid dramatic improvement of the neurological symptoms in 4 cases. However, this initial response did not correlate with the eventual outcome. We reviewed the literature to compare 45 reported cases of MEI associated with a neuroblastoma with 48 children without such a tumor to identify possible differences in clinical presentation, response to steroid medication and long-term prognosis of the neurological syndrome. In this respect we found no differences. Impairment of motor, verbal or intellectual performance were reported in at least half the cases. Although an immediate and marked response to steroids occurs in many cases of both groups, it remains unclear whether the long-term outcome is favourably influenced by this medication. The two-year-survival rate (90%) in the neuroblastoma group and the percentage of mediastinal localisation of the tumor (49%) are much higher compared with neuroblastomas without MEI. The reasons for these remarkable differences are not known. Diagnostic, therapeutic and prognostic implications justify the separation of MEI from the more common and benign syndrome known as acute cerebellar ataxia of childhood.", "contents": "Myoclonic encephalopathy of infants or \"dancing eyes syndrome\". Report of 7 cases with long-term follow-up and review of the literature (cases with and without neuroblastoma). We describe 7 children with myoclonic encephalopathy of infants (MEI). MEI is a clinical entity characterized by an acute or subacute onset of polymyoclonia, cerebellar ataxia and opsoclonus (\"dancing eyes\"). It occurs either spontaneously, following an infectiuos illness or in association with an occult neuroblastoma. It is likely that immunological factors play a role in the pathogenesis. Steroid therapy resulted in rapid dramatic improvement of the neurological symptoms in 4 cases. However, this initial response did not correlate with the eventual outcome. We reviewed the literature to compare 45 reported cases of MEI associated with a neuroblastoma with 48 children without such a tumor to identify possible differences in clinical presentation, response to steroid medication and long-term prognosis of the neurological syndrome. In this respect we found no differences. Impairment of motor, verbal or intellectual performance were reported in at least half the cases. Although an immediate and marked response to steroids occurs in many cases of both groups, it remains unclear whether the long-term outcome is favourably influenced by this medication. The two-year-survival rate (90%) in the neuroblastoma group and the percentage of mediastinal localisation of the tumor (49%) are much higher compared with neuroblastomas without MEI. The reasons for these remarkable differences are not known. Diagnostic, therapeutic and prognostic implications justify the separation of MEI from the more common and benign syndrome known as acute cerebellar ataxia of childhood."}
{"id": "PMID:222714", "title": "Some observations on the phosphatase cytochemistry of the submandibular gland of cat.", "content": "The localization of reaction product arising from incubation with thiamine pyrophosphate at pH 7.2 and beta-glycerophosphate or nitrophenylphosphate at pH 5 has been examined in central and demilunar acinar cells, myoepithelial cells, and cells of the striated ducts. Thiamine pyrophosphate reaction product was seen in the inner saccules of the Golgi apparatuses of the different types of cell. beta-Glycerophosphate and nitrophenylphosphate reaction products were seen in lysosomes, and in GERL-like structures in all except the cells of the striated ducts, in which the reaction products were observed in the Golgi apparatus. In central cells, the latter two reactions products were also seen in secretory granules and the cytosol.", "contents": "Some observations on the phosphatase cytochemistry of the submandibular gland of cat. The localization of reaction product arising from incubation with thiamine pyrophosphate at pH 7.2 and beta-glycerophosphate or nitrophenylphosphate at pH 5 has been examined in central and demilunar acinar cells, myoepithelial cells, and cells of the striated ducts. Thiamine pyrophosphate reaction product was seen in the inner saccules of the Golgi apparatuses of the different types of cell. beta-Glycerophosphate and nitrophenylphosphate reaction products were seen in lysosomes, and in GERL-like structures in all except the cells of the striated ducts, in which the reaction products were observed in the Golgi apparatus. In central cells, the latter two reactions products were also seen in secretory granules and the cytosol."}
{"id": "PMID:222715", "title": "The localization and properties of membrane adenosine triphosphatases in the guinea-pig placenta.", "content": "The distribution and properties of cytochemically demonstrable phosphatases in the near-term guinea-pig placenta were examined using a strontium capture technique for sodium- and potassium-dependent adenosine triphosphatase (Na+, K+-ATPase) and a lead capture technique for magnesium-dependent adenosine triphosphatase (Mg2+-ATPase). Localizations with the strontium technique in the presence of an alkaline phosphatase inhibitor were mainly on the syncytiotrophoblast plasma membranes; the reaction was potassium-dependent and ouabain-sensitive. Reaction product using the lead capture method was found on both trophoblast and endothelial cell plasma membranes and was independent of magnesium and insensitive to p-hydroxymercuribenzoate (POHMB), an inhibitor of membrane ATPases. However, a very large proportion of this reaction could be blocked by an alkaline phosphatase inhibitor. It is concluded that the strontium capture technique gave a reliable localization for Na+, K+-ATPase. However, the lead capture method mainly demonstrated alkaline phosphatase, and does not offer a useful approach to specific ATPase studies in this particular system.", "contents": "The localization and properties of membrane adenosine triphosphatases in the guinea-pig placenta. The distribution and properties of cytochemically demonstrable phosphatases in the near-term guinea-pig placenta were examined using a strontium capture technique for sodium- and potassium-dependent adenosine triphosphatase (Na+, K+-ATPase) and a lead capture technique for magnesium-dependent adenosine triphosphatase (Mg2+-ATPase). Localizations with the strontium technique in the presence of an alkaline phosphatase inhibitor were mainly on the syncytiotrophoblast plasma membranes; the reaction was potassium-dependent and ouabain-sensitive. Reaction product using the lead capture method was found on both trophoblast and endothelial cell plasma membranes and was independent of magnesium and insensitive to p-hydroxymercuribenzoate (POHMB), an inhibitor of membrane ATPases. However, a very large proportion of this reaction could be blocked by an alkaline phosphatase inhibitor. It is concluded that the strontium capture technique gave a reliable localization for Na+, K+-ATPase. However, the lead capture method mainly demonstrated alkaline phosphatase, and does not offer a useful approach to specific ATPase studies in this particular system."}
{"id": "PMID:222716", "title": "Electron spin resonance (ESR) spectrum of paraffin embedded human liver tissue. A possible method for the estimation of copper content.", "content": "Human liver tissues embedded in paraffin wax for histological examination have been studied by Electron Spin Resonance (ESR) spectroscopy. A signal was detected at g approximately 2.05 section of the spectrum. The amplitude of this signal was correlated with the copper content of the embedded specimens measured by flame atomic absorption technique. The positive correlation which has been found can make ESR spectroscopy suitable for estimating the copper content of tissues without damaging the sample. The limits and errors of this method have also been analysed.", "contents": "Electron spin resonance (ESR) spectrum of paraffin embedded human liver tissue. A possible method for the estimation of copper content. Human liver tissues embedded in paraffin wax for histological examination have been studied by Electron Spin Resonance (ESR) spectroscopy. A signal was detected at g approximately 2.05 section of the spectrum. The amplitude of this signal was correlated with the copper content of the embedded specimens measured by flame atomic absorption technique. The positive correlation which has been found can make ESR spectroscopy suitable for estimating the copper content of tissues without damaging the sample. The limits and errors of this method have also been analysed."}
{"id": "PMID:222717", "title": "[The treatment of glomus jugulare tumours (author's transl)].", "content": "Symptoms and signs in 25 patients with glomus jugulare tumours are described. 14 patients with advanced tumours were treated exclusively by irradiation. No case of progression was noted during a follow-up period averaging 7.9 years.", "contents": "[The treatment of glomus jugulare tumours (author's transl)]. Symptoms and signs in 25 patients with glomus jugulare tumours are described. 14 patients with advanced tumours were treated exclusively by irradiation. No case of progression was noted during a follow-up period averaging 7.9 years."}
{"id": "PMID:222718", "title": "[Carotid body and glomus vagale tumours (author's transl)].", "content": "Twentyfour chemodectomas (non-chromaffin paragangliomas) of the neck seen in 20 patients are presented. The investigation including angiography and the surgery in respect to risk factors and preoperative assessment is discussed. The long term results are also presented. Special note is made of the familial incidence since two twin brothers who had bilateral tumours are included.", "contents": "[Carotid body and glomus vagale tumours (author's transl)]. Twentyfour chemodectomas (non-chromaffin paragangliomas) of the neck seen in 20 patients are presented. The investigation including angiography and the surgery in respect to risk factors and preoperative assessment is discussed. The long term results are also presented. Special note is made of the familial incidence since two twin brothers who had bilateral tumours are included."}
{"id": "PMID:222719", "title": "Hydroxyl radical formation in phagocytic cells of the rat.", "content": "Polymorphonuclear leukocytes (PMN) and macrophages, harvested from the peritoneum and lung, release superoxide (O-.2) and hydrogen peroxide (H2O2) during phagocytosis. These two agents are thought to react with each other to produce a highly active oxidative substance known as hydroxyl radical (OH.). We present evidence suggesting that these radicals are generated by phagocytic cells of the rat. Our findings are based upon an assay where ethylene gas is generated from methional by the action of this radical. Ethylene generation was shown to be inhibited by superoxide dismutase, catalase, and scavengers of OH.. Of the cells examined, PMN generated the most ethylene from methional, exhibiting a fourfold increase during phagocytosis. Pulmonary and peritoneal macrophages caused smaller amounts of this gas to be formed. Regardless of cell type, an intact cell was required for ethylene generation. Zymosan appeared to be the most effective particle for all cells in ethylene formation from methional, although opsonization was critical only for PMN. Ethylene generation was dependent on cell concentration to an extent and increased with time.", "contents": "Hydroxyl radical formation in phagocytic cells of the rat. Polymorphonuclear leukocytes (PMN) and macrophages, harvested from the peritoneum and lung, release superoxide (O-.2) and hydrogen peroxide (H2O2) during phagocytosis. These two agents are thought to react with each other to produce a highly active oxidative substance known as hydroxyl radical (OH.). We present evidence suggesting that these radicals are generated by phagocytic cells of the rat. Our findings are based upon an assay where ethylene gas is generated from methional by the action of this radical. Ethylene generation was shown to be inhibited by superoxide dismutase, catalase, and scavengers of OH.. Of the cells examined, PMN generated the most ethylene from methional, exhibiting a fourfold increase during phagocytosis. Pulmonary and peritoneal macrophages caused smaller amounts of this gas to be formed. Regardless of cell type, an intact cell was required for ethylene generation. Zymosan appeared to be the most effective particle for all cells in ethylene formation from methional, although opsonization was critical only for PMN. Ethylene generation was dependent on cell concentration to an extent and increased with time."}
{"id": "PMID:222720", "title": "Longitudinal mixing in pulmonary airways: comparison of inspiration and expiration.", "content": "The increase in dispersion of an inert tracer bolus of helium (He) or sulfur hexafluoride (SF6) was used as a direct and noninvasive measure of longitudinal mixing in the conducting airways. Over a 0- to 260-ml range of bolus penetration, a change in the inspiratory flow from 0.35 to 1.2 l/s did not affect the dispersion of He and SF6, this implies that pure convective dispersion is the dominant inspiratory mixing process. The same change in expiratory flow caused a significant increase in SF6 dispersion only; this indicates that Taylor dispersion is important during expiration. In experiments performed at a fixed penetration of 160 ml and with SF6 only, the inspiratory and the expiratory flows were independently varied from 0.18 to 5.4 l/s. Though the bolus dispersion exhibited a mildly negative correlation with inspiratory flow, it was linearly correlated with expiratory flow. From the former result we conclude that although inspiratory mixing occurs primarily by convective dispersion, there is also a small degree of turbulent dispersion. The latter result confirms that expiratory mixing is primarily due to Taylor dispersion.", "contents": "Longitudinal mixing in pulmonary airways: comparison of inspiration and expiration. The increase in dispersion of an inert tracer bolus of helium (He) or sulfur hexafluoride (SF6) was used as a direct and noninvasive measure of longitudinal mixing in the conducting airways. Over a 0- to 260-ml range of bolus penetration, a change in the inspiratory flow from 0.35 to 1.2 l/s did not affect the dispersion of He and SF6, this implies that pure convective dispersion is the dominant inspiratory mixing process. The same change in expiratory flow caused a significant increase in SF6 dispersion only; this indicates that Taylor dispersion is important during expiration. In experiments performed at a fixed penetration of 160 ml and with SF6 only, the inspiratory and the expiratory flows were independently varied from 0.18 to 5.4 l/s. Though the bolus dispersion exhibited a mildly negative correlation with inspiratory flow, it was linearly correlated with expiratory flow. From the former result we conclude that although inspiratory mixing occurs primarily by convective dispersion, there is also a small degree of turbulent dispersion. The latter result confirms that expiratory mixing is primarily due to Taylor dispersion."}
{"id": "PMID:222724", "title": "Glycogen, hyaluronate, and some other polysaccharides greatly enhance the formation of exolipase by Serratia marcescens.", "content": "Among 21 different polysaccharides tested, 5 greatly enhanced the spontaneous and cyclic AMP-induced formation of exolipase: glycogen, hyaluronate, laminarin, pectin B, and gum arabic. These polysaccharides have in common the tendency to form highly ordered networks because of the branching or helical arrangement, or both, of their molecules. None of the polysaccharides could be utilized by the cells as the sole carbon source. Strong lipid extraction of four different polysaccharides did not reduce their exolipase-enhancing efficacy. At a constant cell density the stimulation of exolipase formation by various concentrations of glycogen followed saturation kinetics, suggesting a limited number of \"sites\" for the glycogen to act. The active principle present in a solution of pectin was destroyed by degradation (beta-elimination) of the polymer. Hyaluronate lost its exolipase-enhancing activity by exhaustive hydrolysis with hyaluronidase but was resistant to proteinase K. Exopolysaccharide, isolated from growth medium of Serratia marcescens SM-6, enhanced the exolipase formation as efficiently as hyaluronate. The results of this work are discussed mainly in terms of the \"detachment hypothesis.\"", "contents": "Glycogen, hyaluronate, and some other polysaccharides greatly enhance the formation of exolipase by Serratia marcescens. Among 21 different polysaccharides tested, 5 greatly enhanced the spontaneous and cyclic AMP-induced formation of exolipase: glycogen, hyaluronate, laminarin, pectin B, and gum arabic. These polysaccharides have in common the tendency to form highly ordered networks because of the branching or helical arrangement, or both, of their molecules. None of the polysaccharides could be utilized by the cells as the sole carbon source. Strong lipid extraction of four different polysaccharides did not reduce their exolipase-enhancing efficacy. At a constant cell density the stimulation of exolipase formation by various concentrations of glycogen followed saturation kinetics, suggesting a limited number of \"sites\" for the glycogen to act. The active principle present in a solution of pectin was destroyed by degradation (beta-elimination) of the polymer. Hyaluronate lost its exolipase-enhancing activity by exhaustive hydrolysis with hyaluronidase but was resistant to proteinase K. Exopolysaccharide, isolated from growth medium of Serratia marcescens SM-6, enhanced the exolipase formation as efficiently as hyaluronate. The results of this work are discussed mainly in terms of the \"detachment hypothesis.\""}
{"id": "PMID:222725", "title": "Effects of 8-substituted analogs of cyclic adenosine 3',5'-monophosphate on in vivo and in vitro syntheses of beta-galactosidase in Escherichia coli.", "content": "Several 8-substituted alkylthio and alkylamino cyclic adenosine 3',5'-monophosphate (cAMP) derivatives were tested for their ability to stimulate beta-galactosidase synthesis in Estherichia coli in vivo and in vitro and to inhibit the cAMP phosphodiesterase activity of E. coli. Stimulation of beta-galactosidease synthesis in vivo by cAMP derivatives decreased with increasing length of the unbranched carbon chain of the substituent. On the other hand, the stimulation in vitro was increased as the carbon chain elongated. The 8-decylthio- and 8-dodecylthio-cAMP compounds stimulated beta-galactosidase synthesis almost eight-fold compared with cAMP, whereas 8-undecyl-, 8-dodectyl-, and 8-tridecylamino-cAMP stimulated beta-galactosidase synthesis about threefold. However, in in vitro experiments with a phosphodiesterase-deficient strain of E. coli, the Crooks strain, the stimulatory effects of the derivatives disappeared, except for 8-dodecylthio cAMP which stimulated beta-galactosidase about 1.4- to 1.6-fold. All derivatives were quite resistant to hydrolysis by phosphodiesterase. Most derivatives competitively inhibited the hydrolysis of cAMP by phosphodiesterase.", "contents": "Effects of 8-substituted analogs of cyclic adenosine 3',5'-monophosphate on in vivo and in vitro syntheses of beta-galactosidase in Escherichia coli. Several 8-substituted alkylthio and alkylamino cyclic adenosine 3',5'-monophosphate (cAMP) derivatives were tested for their ability to stimulate beta-galactosidase synthesis in Estherichia coli in vivo and in vitro and to inhibit the cAMP phosphodiesterase activity of E. coli. Stimulation of beta-galactosidease synthesis in vivo by cAMP derivatives decreased with increasing length of the unbranched carbon chain of the substituent. On the other hand, the stimulation in vitro was increased as the carbon chain elongated. The 8-decylthio- and 8-dodecylthio-cAMP compounds stimulated beta-galactosidase synthesis almost eight-fold compared with cAMP, whereas 8-undecyl-, 8-dodectyl-, and 8-tridecylamino-cAMP stimulated beta-galactosidase synthesis about threefold. However, in in vitro experiments with a phosphodiesterase-deficient strain of E. coli, the Crooks strain, the stimulatory effects of the derivatives disappeared, except for 8-dodecylthio cAMP which stimulated beta-galactosidase about 1.4- to 1.6-fold. All derivatives were quite resistant to hydrolysis by phosphodiesterase. Most derivatives competitively inhibited the hydrolysis of cAMP by phosphodiesterase."}
{"id": "PMID:222726", "title": "Chemical alterations in cell envelopes of polymyxin-resistant Pseudomonas aeruginosa isolates.", "content": "Cell envelopes from Pseudomonas aeruginosa strains resistant to polymyxin were compared with cell envelopes from polymyxin-sensitive strains as to their content of total protein, carbohydrate, and 2-keto-3-deoxyoctonate and as to their protein composition as determined by slab polyacrylamide gel electrophoresis. The cell envelopes of the polymyxin-resistant strains had reduced amounts of lipopolysaccharide, as indicated a reduction in both carbohydrate and 2-keto-3-deoxyoctonate concentrations, and a greatly altered protein composition as shown by polyacrylamide gel electrophoresis. There was a quantitative increase in total cell envelop protein in these strains. However, those protein bands identified as being major outer membrane proteins upon polyacrylamide gel electrophoresis of separated outer and cytoplasmic membranes were reduced greatly in concentration in the polymyxin-resistant cell envelopes. Thus, it appears that polymyxin resistance in these strains is associated with the alteration of the outer membrane through a loss of lipopolysaccharide and outer membrane proteins.", "contents": "Chemical alterations in cell envelopes of polymyxin-resistant Pseudomonas aeruginosa isolates. Cell envelopes from Pseudomonas aeruginosa strains resistant to polymyxin were compared with cell envelopes from polymyxin-sensitive strains as to their content of total protein, carbohydrate, and 2-keto-3-deoxyoctonate and as to their protein composition as determined by slab polyacrylamide gel electrophoresis. The cell envelopes of the polymyxin-resistant strains had reduced amounts of lipopolysaccharide, as indicated a reduction in both carbohydrate and 2-keto-3-deoxyoctonate concentrations, and a greatly altered protein composition as shown by polyacrylamide gel electrophoresis. There was a quantitative increase in total cell envelop protein in these strains. However, those protein bands identified as being major outer membrane proteins upon polyacrylamide gel electrophoresis of separated outer and cytoplasmic membranes were reduced greatly in concentration in the polymyxin-resistant cell envelopes. Thus, it appears that polymyxin resistance in these strains is associated with the alteration of the outer membrane through a loss of lipopolysaccharide and outer membrane proteins."}
{"id": "PMID:222727", "title": "Yeast cytochrome c-specific protein-lysine methyltransferase: coordinate regulation with cytochrome c and activities in cyc mutants.", "content": "The cytochromes c of fungi and higher plants contain one or two residues of epsilon-N-trimethyllysine, whose biological role is unknown. A cytochrome c-specific S-adenosylmethionine:protein-sysine methyltransferase (methylase) activity was shown to be present in extracts of the bakers' yeast Saccharomyces cerevisiae, and basic kinetic properties of this enzyme are described. The specific activity of the methylase was lower in extracts of cells grown under conditions of catabolite (glucose) repression or anaerobiosis where cytochrome c levels were low, compared with cells grown under derepressed conditions where cytochrome c levels were high. During anaerobic-to-aerobic adaptation, the methylase was induced in parallel with cytochrome c, thus suggesting that the syntheses of cytochrome c and cytochrome c methylase are coordinately regulated. None of the cyc strains surveyed (cyc1, cyc2, cyc3, cyc4, cyc5, and cyc6) had diminished levels of methylase, although some of them were completely or almost completely deficient in cytochrome c.", "contents": "Yeast cytochrome c-specific protein-lysine methyltransferase: coordinate regulation with cytochrome c and activities in cyc mutants. The cytochromes c of fungi and higher plants contain one or two residues of epsilon-N-trimethyllysine, whose biological role is unknown. A cytochrome c-specific S-adenosylmethionine:protein-sysine methyltransferase (methylase) activity was shown to be present in extracts of the bakers' yeast Saccharomyces cerevisiae, and basic kinetic properties of this enzyme are described. The specific activity of the methylase was lower in extracts of cells grown under conditions of catabolite (glucose) repression or anaerobiosis where cytochrome c levels were low, compared with cells grown under derepressed conditions where cytochrome c levels were high. During anaerobic-to-aerobic adaptation, the methylase was induced in parallel with cytochrome c, thus suggesting that the syntheses of cytochrome c and cytochrome c methylase are coordinately regulated. None of the cyc strains surveyed (cyc1, cyc2, cyc3, cyc4, cyc5, and cyc6) had diminished levels of methylase, although some of them were completely or almost completely deficient in cytochrome c."}
{"id": "PMID:222728", "title": "Aromatic amino acid biosynthesis: regulation of shikimate kinase in Escherichia coli K-12.", "content": "Starvation of cells of Escherichia coli K-12 for the aromatic amino acids results in an increased rate of synthesis of shikimate kinase activity. The two controlling amino acids are tyrosine and tryptophan, and starvation for both results in derepression. The product of the regulator gene tyrR also participates in this control, and shikimate kinase synthesis was depressed in tyrR mutants. Chromatography of cell extracts on diethylaminoethyl-Sephadex allowed partial separation of two shikimate kinase enzymes and demonstrated that only one of these subject to specific repression control involving tyrR. By contrast, chromatography of cell extracts with G-75 or G-200 columns revealed a singl-molecular-weight species of shikimate kinase activity with an apparent molecular weight of 20,000. The levels of shikimate kinase in a series of partial diploid strains indicated that aroL, the structural gene for the tyrR-controlled shikimate kinase enzyme, is located on the E. coli chromosome between the structural genes proC and purE. By means of localized mutagenesis, an aroL mutant of E. coli was isolated. The mutant was an aromatic prototroph and, by the criterion of column chromatography, appeared to have only a single functional species of shikimate kinase enzyme.", "contents": "Aromatic amino acid biosynthesis: regulation of shikimate kinase in Escherichia coli K-12. Starvation of cells of Escherichia coli K-12 for the aromatic amino acids results in an increased rate of synthesis of shikimate kinase activity. The two controlling amino acids are tyrosine and tryptophan, and starvation for both results in derepression. The product of the regulator gene tyrR also participates in this control, and shikimate kinase synthesis was depressed in tyrR mutants. Chromatography of cell extracts on diethylaminoethyl-Sephadex allowed partial separation of two shikimate kinase enzymes and demonstrated that only one of these subject to specific repression control involving tyrR. By contrast, chromatography of cell extracts with G-75 or G-200 columns revealed a singl-molecular-weight species of shikimate kinase activity with an apparent molecular weight of 20,000. The levels of shikimate kinase in a series of partial diploid strains indicated that aroL, the structural gene for the tyrR-controlled shikimate kinase enzyme, is located on the E. coli chromosome between the structural genes proC and purE. By means of localized mutagenesis, an aroL mutant of E. coli was isolated. The mutant was an aromatic prototroph and, by the criterion of column chromatography, appeared to have only a single functional species of shikimate kinase enzyme."}
{"id": "PMID:222729", "title": "Pyridine nucleotide cycle of Salmonella typhimurium: regulation of nicotinic acid phosphoribosyltransferase and nicotinamide deamidase.", "content": "Nicotinic acid phosphoribosyl transferase (NAPRTase) and nicotinamide deamidase activities from Salmonella typhimurium were examined regarding their regulation by either feedback inhibition or repression mechanisms. The results indicate that neither enzyme is subject to feedback inhbition. Nicotinamide deamidase does not appear to be under repression control. NAPRTase, however, is repressed when cells are grown in minimal medium supplemented with various intermediates of the pyridine nucleotide cycle. The concentration of exogenously supplied pyridine nucleotide necessary to effect repression of NAPRTas was found to be that concentration which will result in a nadA mutant generation time of less than 60 min. Furthermore, the results presented indicate that nicotinamide adenine dinucleotide is the actual corepressor molecule. The analogs 6-aminonicotinic acid and 6-aminonicotinamide were also capable of repressing NAPRTase, but only when an intact pyridine nucleotide cycl permitted conversion to 6-aminonicotinamide adenine dinucleotide. The role of a repressible NAPRTase is discussed in relation to the overall functioning of the pyridine nucleotide cycle.", "contents": "Pyridine nucleotide cycle of Salmonella typhimurium: regulation of nicotinic acid phosphoribosyltransferase and nicotinamide deamidase. Nicotinic acid phosphoribosyl transferase (NAPRTase) and nicotinamide deamidase activities from Salmonella typhimurium were examined regarding their regulation by either feedback inhibition or repression mechanisms. The results indicate that neither enzyme is subject to feedback inhbition. Nicotinamide deamidase does not appear to be under repression control. NAPRTase, however, is repressed when cells are grown in minimal medium supplemented with various intermediates of the pyridine nucleotide cycle. The concentration of exogenously supplied pyridine nucleotide necessary to effect repression of NAPRTas was found to be that concentration which will result in a nadA mutant generation time of less than 60 min. Furthermore, the results presented indicate that nicotinamide adenine dinucleotide is the actual corepressor molecule. The analogs 6-aminonicotinic acid and 6-aminonicotinamide were also capable of repressing NAPRTase, but only when an intact pyridine nucleotide cycl permitted conversion to 6-aminonicotinamide adenine dinucleotide. The role of a repressible NAPRTase is discussed in relation to the overall functioning of the pyridine nucleotide cycle."}
{"id": "PMID:222730", "title": "Orientation of the guanine operon of Escherichia coli K-12 by utilizing strains containing guaB-xse and guaB-upp deletions.", "content": "Temperature induction of an Escherichia coli strains with lambda cI1857 integrated in the guaB gene has been used to produce strains containing chromosomal deletions extending into the xse and upp genes. By utilizing strains containing these deletions, it has been possible to order the genes in the guanine operon with respect to the xseA and upp genes. The order of the genes in this region is glyA-hisS-xseA-guaO-guaB-guaA-purG-upp-purC.", "contents": "Orientation of the guanine operon of Escherichia coli K-12 by utilizing strains containing guaB-xse and guaB-upp deletions. Temperature induction of an Escherichia coli strains with lambda cI1857 integrated in the guaB gene has been used to produce strains containing chromosomal deletions extending into the xse and upp genes. By utilizing strains containing these deletions, it has been possible to order the genes in the guanine operon with respect to the xseA and upp genes. The order of the genes in this region is glyA-hisS-xseA-guaO-guaB-guaA-purG-upp-purC."}
{"id": "PMID:222731", "title": "Uptake and catabolism of D-xylose in Salmonella typhimurium LT2.", "content": "Salmonella typhimurium LT2 grows on D-xylose as sole carbon source with a generation time of 105 to 110 min. The following activities are induced at the indicated time after the addition of the inducer, D-xylose: D-xylulokinase (5 min), D-xylose isomerase (7 to 8 min), and D-xylose transport (10 min). All other pentoses and pentitols tested failed to induce isomerase or kinase. Synthesis of D-xylose isomerase was subject to catabolite repression, which was reversed by the addition of cyclic adenosine monophosphate. Most of the radioactive counts from D-[14C]xylose were initially accumulated in the cell in the form of D-xylose or D-xylulose. D-Xylose uptake in a mutant which was deficient in D-xylose isomerase was equal to that of the wild type. The apparent Km for D-xylose uptake was 0.41 mM. Some L-arabinose was accumulated in D-xylose-induced cells, and some D-xylose was accumulated in L-arabinose-induced cells. D-Xylitol and L-arabinose competed against C-xylose uptake, but D-arabinose, D-lyxose, and L-lyxose did not. Osmotic shock reduced the uptake of D-xylose by about 50%; by equilibrium dialysis, a D-xylose-binding protein was detected in the supernatant fluid after spheroplasts were formed from D-xylose-induced cells.", "contents": "Uptake and catabolism of D-xylose in Salmonella typhimurium LT2. Salmonella typhimurium LT2 grows on D-xylose as sole carbon source with a generation time of 105 to 110 min. The following activities are induced at the indicated time after the addition of the inducer, D-xylose: D-xylulokinase (5 min), D-xylose isomerase (7 to 8 min), and D-xylose transport (10 min). All other pentoses and pentitols tested failed to induce isomerase or kinase. Synthesis of D-xylose isomerase was subject to catabolite repression, which was reversed by the addition of cyclic adenosine monophosphate. Most of the radioactive counts from D-[14C]xylose were initially accumulated in the cell in the form of D-xylose or D-xylulose. D-Xylose uptake in a mutant which was deficient in D-xylose isomerase was equal to that of the wild type. The apparent Km for D-xylose uptake was 0.41 mM. Some L-arabinose was accumulated in D-xylose-induced cells, and some D-xylose was accumulated in L-arabinose-induced cells. D-Xylitol and L-arabinose competed against C-xylose uptake, but D-arabinose, D-lyxose, and L-lyxose did not. Osmotic shock reduced the uptake of D-xylose by about 50%; by equilibrium dialysis, a D-xylose-binding protein was detected in the supernatant fluid after spheroplasts were formed from D-xylose-induced cells."}
{"id": "PMID:222732", "title": "Genetics and regulation of D-xylose utilization in Salmonella typhimurium LT2.", "content": "Twenty-one Xyl- mutants of Salmonella typhimurium were selected: all had lost one or more of the activities for D-xylose isomerase, C-xylulokinase, or D-xylose transport. The mutants were classified into five functional groups: xylR, pleiotropic negative (12 mutants); xylA, D-xylose isomerase defective (3 mutants); xylB, D-xylulokinase defective (2 mutants); xylT, D-xylose transport defective (1 mutant); and 3 mutants with defective D-xylose isomerase and D-xylulokinase. Some nonsense mutations were identified among the xylR mutants. Two F'xyl plasmids were isolated by selection for early transfer of xyl+ by an Hfr which transfers xyl as a terminal gene; a plasmid with a mutation in the xyl genes, F'xylR1, was also isolated. Complementation tests using F'xyl plasmids indicate that expression of the xylA, xylB, and xylT genes is under the positive control of the xylR regulatory gene. Conjugation crosses and P22-mediated transduction data indicate that all the xyl mutations tested are in a cluster of genes at 78 units on the linkage map, and that the gene order is xylT--xylR--xylB--xylA--glyS--mtlA,D.", "contents": "Genetics and regulation of D-xylose utilization in Salmonella typhimurium LT2. Twenty-one Xyl- mutants of Salmonella typhimurium were selected: all had lost one or more of the activities for D-xylose isomerase, C-xylulokinase, or D-xylose transport. The mutants were classified into five functional groups: xylR, pleiotropic negative (12 mutants); xylA, D-xylose isomerase defective (3 mutants); xylB, D-xylulokinase defective (2 mutants); xylT, D-xylose transport defective (1 mutant); and 3 mutants with defective D-xylose isomerase and D-xylulokinase. Some nonsense mutations were identified among the xylR mutants. Two F'xyl plasmids were isolated by selection for early transfer of xyl+ by an Hfr which transfers xyl as a terminal gene; a plasmid with a mutation in the xyl genes, F'xylR1, was also isolated. Complementation tests using F'xyl plasmids indicate that expression of the xylA, xylB, and xylT genes is under the positive control of the xylR regulatory gene. Conjugation crosses and P22-mediated transduction data indicate that all the xyl mutations tested are in a cluster of genes at 78 units on the linkage map, and that the gene order is xylT--xylR--xylB--xylA--glyS--mtlA,D."}
{"id": "PMID:222733", "title": "Arylsulfatase in Salmonella typhimurium: detection and influence of carbon source and tyramine on its synthesis.", "content": "Arylsulfatase synthesis was shown to occur in Salmonella typhimurium LT2. The enzyme had a molecular weight of approximately 50,000 and was separated into five forms by isoelectrofocusing. The optimal pH for substrate hydrolysis was pH 6.7, with Michaelis constants for nitrocatechol sulfate and nitrophenyl sulfate being 4.1 and 7.9 mM, respectively. Enzyme synthesis was strongly influenced by the presence of tyramine in the growth medium. The uptake of [14C]tyramine and arylsulfatase synthesis were initiated during the second phase of a diauxie growth response, when the organism was cultured with different carbon sources. Adenosine 3',5'-cyclic monophosphoric acid enhanced the uptake of tyramine and the levels of arylsulfatase synthesized. However, the addition of glucose and glycerol to organisms actively transporting tyramine and synthesizing enzyme caused a rapid inhibition of both of these processes. This inhibition was not reversed by adding adenosine 3',5'-cyclic monophosphoric acid. The results suggest that the effect of the carbon source on tyramine transport and arylsulfatase synthesis may be explained in terms of inducer exclusion.", "contents": "Arylsulfatase in Salmonella typhimurium: detection and influence of carbon source and tyramine on its synthesis. Arylsulfatase synthesis was shown to occur in Salmonella typhimurium LT2. The enzyme had a molecular weight of approximately 50,000 and was separated into five forms by isoelectrofocusing. The optimal pH for substrate hydrolysis was pH 6.7, with Michaelis constants for nitrocatechol sulfate and nitrophenyl sulfate being 4.1 and 7.9 mM, respectively. Enzyme synthesis was strongly influenced by the presence of tyramine in the growth medium. The uptake of [14C]tyramine and arylsulfatase synthesis were initiated during the second phase of a diauxie growth response, when the organism was cultured with different carbon sources. Adenosine 3',5'-cyclic monophosphoric acid enhanced the uptake of tyramine and the levels of arylsulfatase synthesized. However, the addition of glucose and glycerol to organisms actively transporting tyramine and synthesizing enzyme caused a rapid inhibition of both of these processes. This inhibition was not reversed by adding adenosine 3',5'-cyclic monophosphoric acid. The results suggest that the effect of the carbon source on tyramine transport and arylsulfatase synthesis may be explained in terms of inducer exclusion."}
{"id": "PMID:222734", "title": "Neisseria gonorrhoeae membrane microenvironment studied by spin-label electron spin resonance: comparison of colony types.", "content": "Spin-label electron spin resonance was used to characterize the microenvironment around spin probes which localize (i) in membranes, (ii) at the membrane surface, or (iii) in the cytoplasm of living Neisseria gonorrhoeae. Four colony types (T1, T2, T3, and T4) of gonococci were compared on the basis of the electron spin resonance parameters 2T parallel to, S (order parameter), and tau c (microviscosity). The concentration of spin label used had little or no effect on viability. T1 and T2 gonococci were found to have a more restricted environment for molecular motion of a membrane surface spin label than did T3 and T4. The membrane fluidity, as measured by a membrane lipid spin label, of T4 (S = 0.571) was significantly greater than that of T1 or T3 (S = 0.580). This difference was detected at 37 degrees C, at 25 degrees C, in agar-grown bacteria, and in exponential-phase cells. Studies using spin labels which probe different levels of the membrane indicated the presence of a membrane flexibility gradient. Cytoplasmic spin-label studies indicated that the cytoplasm of all gonococcal colony types was three to five times more viscous than water.", "contents": "Neisseria gonorrhoeae membrane microenvironment studied by spin-label electron spin resonance: comparison of colony types. Spin-label electron spin resonance was used to characterize the microenvironment around spin probes which localize (i) in membranes, (ii) at the membrane surface, or (iii) in the cytoplasm of living Neisseria gonorrhoeae. Four colony types (T1, T2, T3, and T4) of gonococci were compared on the basis of the electron spin resonance parameters 2T parallel to, S (order parameter), and tau c (microviscosity). The concentration of spin label used had little or no effect on viability. T1 and T2 gonococci were found to have a more restricted environment for molecular motion of a membrane surface spin label than did T3 and T4. The membrane fluidity, as measured by a membrane lipid spin label, of T4 (S = 0.571) was significantly greater than that of T1 or T3 (S = 0.580). This difference was detected at 37 degrees C, at 25 degrees C, in agar-grown bacteria, and in exponential-phase cells. Studies using spin labels which probe different levels of the membrane indicated the presence of a membrane flexibility gradient. Cytoplasmic spin-label studies indicated that the cytoplasm of all gonococcal colony types was three to five times more viscous than water."}
{"id": "PMID:222735", "title": "Effects of cerulenin upon the syntheses of lipid and protein and upon the formation of respiratory enzymes in adapting, lipid-limited Saccharomyces cerevisiae.", "content": "When bakers' yeast cells were grown anaerobically in a medium supplemented with Tween 80 and ergosterol, exposure during aeration to the fatty acid synthesis inhibitor, cerulenin, had little effect upon respiratory adaptation, the induction of enzymes of electron transport, or the in vivo incorporation of [(14)C]leucine into mitochondrial membranes. These lipid-supplemented cells were apparently able to undergo normal respiratory adaptation utilizing endogenous lipids alone. The level of cerulenin used (2 mug/ml) inhibited the in vivo incorporation of [(14)C]acetate into mitochondrial membrane lipids by 96%. If, however, the cells were deprived of exogenous lipid during anaerobic growth, subsequent exposure to cerulenin severely reduced their capacity to undergo respiratory adaptation, to form enzymes of electron transport, and to incorporate amino acid into both total cell and mitochondrial membrane proteins. This cerulenin-mediated inhibition of enzyme formation and of protein synthesis was nearly completely reversed by the addition of exogenous lipid during the aeration of the cells. In lipid-limited cells, chloramphenicol also had dramatic inhibitory effects, both alone (75%) and together with cerulenin (85%), upon total cell and mitochondrial membrane [(14)C]leucine incorporation. This marked chloramphenicol-mediated inhibition was also largely reversed by exogenous lipid. It is concluded that, in lipid-limited cells, either cerulenin or chloramphenicol may prevent the emergence of a pattern of lipids required for normal levels of protein synthetic activity. The effect of cerulenin upon the formation of mitochondrial inner membrane enzymes thus appears to reflect a nonspecific effect of this antilipogenic antibiotic upon total cell protein synthesis.", "contents": "Effects of cerulenin upon the syntheses of lipid and protein and upon the formation of respiratory enzymes in adapting, lipid-limited Saccharomyces cerevisiae. When bakers' yeast cells were grown anaerobically in a medium supplemented with Tween 80 and ergosterol, exposure during aeration to the fatty acid synthesis inhibitor, cerulenin, had little effect upon respiratory adaptation, the induction of enzymes of electron transport, or the in vivo incorporation of [(14)C]leucine into mitochondrial membranes. These lipid-supplemented cells were apparently able to undergo normal respiratory adaptation utilizing endogenous lipids alone. The level of cerulenin used (2 mug/ml) inhibited the in vivo incorporation of [(14)C]acetate into mitochondrial membrane lipids by 96%. If, however, the cells were deprived of exogenous lipid during anaerobic growth, subsequent exposure to cerulenin severely reduced their capacity to undergo respiratory adaptation, to form enzymes of electron transport, and to incorporate amino acid into both total cell and mitochondrial membrane proteins. This cerulenin-mediated inhibition of enzyme formation and of protein synthesis was nearly completely reversed by the addition of exogenous lipid during the aeration of the cells. In lipid-limited cells, chloramphenicol also had dramatic inhibitory effects, both alone (75%) and together with cerulenin (85%), upon total cell and mitochondrial membrane [(14)C]leucine incorporation. This marked chloramphenicol-mediated inhibition was also largely reversed by exogenous lipid. It is concluded that, in lipid-limited cells, either cerulenin or chloramphenicol may prevent the emergence of a pattern of lipids required for normal levels of protein synthetic activity. The effect of cerulenin upon the formation of mitochondrial inner membrane enzymes thus appears to reflect a nonspecific effect of this antilipogenic antibiotic upon total cell protein synthesis."}
{"id": "PMID:222736", "title": "Cardiolipin accumulation in the inner and outer membranes of Escherichia coli mutants defective in phosphatidylserine synthetase.", "content": "Mutants of Escherichia coli defective in phosphatidylserine synthetase (pss) make less phosphatidylethanolamine than normal cells, and they are temperature sensitive for growth. We have isolated a new mutant, designated RA2021, which is better than previously available strains in that the residual phosphatidylethanolamine level approaches 25% after 4 h at 42 degrees C. The total amount of phospholipid normalized to the density of the culture is about the same in RA2021 (pss-21) as in the isogenic wild-type RA2000 (pss(+)). Consequently, there is a net accumulation of polyglycerophosphatides in the mutant, particularly of cardiolipin. The addition of 10 to 20 mM MgCl(2) to a culture of RA2021 prolongs growth under nonpermissive conditions and prevents loss of cell viability, but it does not eliminate the temperature-sensitive phenotype. Divalent cations, like Mg(2+), do not correct the phospholipid composition of the mutant, but may act indirectly by balancing the negative charges of phosphatidylglycerol and cardiolipin. To determine the effects of the pss mutation on membrane composition, we have examined the subcellular distribution of the polyglycerophosphatides that accumulate in these strains. All of the excess anionic lipids of RA2021 are associated with the envelope fraction and are distributed equally between the inner and outer membranes. The protein compositions of the isolated membranes do not differ significantly in the mutant and wild type. The fatty acid composition of RA2021 is almost the same as wild type at 30 degrees C, but there is more palmitic and cyclopropane fatty acid at 42 degrees C. These results demonstrate that the modification of the polar lipid composition observed in pss mutants affects both membranes and that cardiolipin, which is not ordinarily present in large quantities, can accumulate in the outer membrane when it is overproduced by the cell. The altered polar headgroup composition of the outer membrane in pss mutants may account, in part, for their hypersensitivity to the aminoglycoside antibiotics.", "contents": "Cardiolipin accumulation in the inner and outer membranes of Escherichia coli mutants defective in phosphatidylserine synthetase. Mutants of Escherichia coli defective in phosphatidylserine synthetase (pss) make less phosphatidylethanolamine than normal cells, and they are temperature sensitive for growth. We have isolated a new mutant, designated RA2021, which is better than previously available strains in that the residual phosphatidylethanolamine level approaches 25% after 4 h at 42 degrees C. The total amount of phospholipid normalized to the density of the culture is about the same in RA2021 (pss-21) as in the isogenic wild-type RA2000 (pss(+)). Consequently, there is a net accumulation of polyglycerophosphatides in the mutant, particularly of cardiolipin. The addition of 10 to 20 mM MgCl(2) to a culture of RA2021 prolongs growth under nonpermissive conditions and prevents loss of cell viability, but it does not eliminate the temperature-sensitive phenotype. Divalent cations, like Mg(2+), do not correct the phospholipid composition of the mutant, but may act indirectly by balancing the negative charges of phosphatidylglycerol and cardiolipin. To determine the effects of the pss mutation on membrane composition, we have examined the subcellular distribution of the polyglycerophosphatides that accumulate in these strains. All of the excess anionic lipids of RA2021 are associated with the envelope fraction and are distributed equally between the inner and outer membranes. The protein compositions of the isolated membranes do not differ significantly in the mutant and wild type. The fatty acid composition of RA2021 is almost the same as wild type at 30 degrees C, but there is more palmitic and cyclopropane fatty acid at 42 degrees C. These results demonstrate that the modification of the polar lipid composition observed in pss mutants affects both membranes and that cardiolipin, which is not ordinarily present in large quantities, can accumulate in the outer membrane when it is overproduced by the cell. The altered polar headgroup composition of the outer membrane in pss mutants may account, in part, for their hypersensitivity to the aminoglycoside antibiotics."}
{"id": "PMID:222737", "title": "Localization of dolichyl phosphate- and pyrophosphate-dependent glycosyl transfer reactions in Saccharomyces cerevisiae.", "content": "Membranes from Saccharomyces cerevisiae protoplasts were fractionated on a continuous sucrose gradient. Six bands were obtained, which contained altogether about 15% of the total cell protein. From their densitites, their behavior in the presence and absence of Mg2+ ions, and the distribution of marker enzymes, it was possible to identify fractions enriched in rough and smooth endoplasmic reticulum and in mitochondria. All glycosyl transfer reactions investigated where dolichyl phosphates served as glycosyl acceptors or where dolichyl phosphate- and pyrophosphate-activated sugars served as glycosyl donors showed the highest specific activity and up to 75% of the total activity in the endoplasmic reticulum. This was the case for the reactions involved in the formation of O-glycosidic as well as N-glycosidic linkages in yeast glycoprotein biosynthesis. Membrane fractions enriched in plasmalemma contained less than 3% of the corresponding activities.", "contents": "Localization of dolichyl phosphate- and pyrophosphate-dependent glycosyl transfer reactions in Saccharomyces cerevisiae. Membranes from Saccharomyces cerevisiae protoplasts were fractionated on a continuous sucrose gradient. Six bands were obtained, which contained altogether about 15% of the total cell protein. From their densitites, their behavior in the presence and absence of Mg2+ ions, and the distribution of marker enzymes, it was possible to identify fractions enriched in rough and smooth endoplasmic reticulum and in mitochondria. All glycosyl transfer reactions investigated where dolichyl phosphates served as glycosyl acceptors or where dolichyl phosphate- and pyrophosphate-activated sugars served as glycosyl donors showed the highest specific activity and up to 75% of the total activity in the endoplasmic reticulum. This was the case for the reactions involved in the formation of O-glycosidic as well as N-glycosidic linkages in yeast glycoprotein biosynthesis. Membrane fractions enriched in plasmalemma contained less than 3% of the corresponding activities."}
{"id": "PMID:222738", "title": "Decreased binding of polymyxin by polymyxin-resistant mutants of Salmonella typhimurium.", "content": "Polymyxin-resistant pmrA strains were shown to absorb only about 25% of the amount of polymyxin absorbed by the corresponding polymyxin-sensitive parent strains. The lipopolysaccharide from the pmrA strains bound less polymyxin than the lipopolysaccharide from the parent strains.", "contents": "Decreased binding of polymyxin by polymyxin-resistant mutants of Salmonella typhimurium. Polymyxin-resistant pmrA strains were shown to absorb only about 25% of the amount of polymyxin absorbed by the corresponding polymyxin-sensitive parent strains. The lipopolysaccharide from the pmrA strains bound less polymyxin than the lipopolysaccharide from the parent strains."}
{"id": "PMID:222739", "title": "Microbial oxidation of gaseous hydrocarbons. II. Hydroxylation of alkanes and epoxidation of alkenes by cell-free particulate fractions of methane-utilizing bacteria.", "content": "Cell-free particulate fractions derived from methylotrophic bacteria catalyze the oxygen- and reduced nicotinamide adenine dinucleotide-dependent epoxidation of alkenes and hydroxylation of alkanes. Evidence presented indicates that the hydroxylation and epoxidation reactions are catalyzed by the same or a similar metal-containing monooxygenase.", "contents": "Microbial oxidation of gaseous hydrocarbons. II. Hydroxylation of alkanes and epoxidation of alkenes by cell-free particulate fractions of methane-utilizing bacteria. Cell-free particulate fractions derived from methylotrophic bacteria catalyze the oxygen- and reduced nicotinamide adenine dinucleotide-dependent epoxidation of alkenes and hydroxylation of alkanes. Evidence presented indicates that the hydroxylation and epoxidation reactions are catalyzed by the same or a similar metal-containing monooxygenase."}
{"id": "PMID:222740", "title": "Antipain lethality to Escherichia coli: dependence upon cyclic adenosine 3',5'-monophosphate and its receptor protein.", "content": "Antipain kills Escherichia coli K-12 cells in an exponential manner beginning 1 h after its addition. Mutant strains, delta cya and crp, which are unable to synthesize cyclic adenosine 3',5'-monophosphate (cAMP) and the cAMP receptor protein, respectively, are not affected. Addition of cAMP (5 mM) to antipain-treated mutant strains causes killing of delta cya cells, but not crp cells. Thus the lethal effect of antipain is dependent upon cAMP and its receptor protein.", "contents": "Antipain lethality to Escherichia coli: dependence upon cyclic adenosine 3',5'-monophosphate and its receptor protein. Antipain kills Escherichia coli K-12 cells in an exponential manner beginning 1 h after its addition. Mutant strains, delta cya and crp, which are unable to synthesize cyclic adenosine 3',5'-monophosphate (cAMP) and the cAMP receptor protein, respectively, are not affected. Addition of cAMP (5 mM) to antipain-treated mutant strains causes killing of delta cya cells, but not crp cells. Thus the lethal effect of antipain is dependent upon cAMP and its receptor protein."}
{"id": "PMID:222741", "title": "Analgesia and haloperidol: a hypothesis.", "content": "We have previously reported 10 patient histories involving various intractable pain syndromes where the administration of Haloperidol either eliminated the need for narcotic analgesics or resulted in a significant reduction in narcotic dosage. We are presently undertaking a controlled double-blind evaluation of Haloperidol as an adjunctive treatment for intractable cancer pain. Based upon the reported clinical observations, these findings are discussed from the following aspects: 1. The isomeric similarity of Haloperidol to Meperidine. 2. Dose response between Haloperidol and analgesic effect. 3. The clinical literature regarding the use of Haloperidol for the effective withdrawal or maintenance of narcotic addicts. 4. The analgesic property as it relates to the opiate receptor.", "contents": "Analgesia and haloperidol: a hypothesis. We have previously reported 10 patient histories involving various intractable pain syndromes where the administration of Haloperidol either eliminated the need for narcotic analgesics or resulted in a significant reduction in narcotic dosage. We are presently undertaking a controlled double-blind evaluation of Haloperidol as an adjunctive treatment for intractable cancer pain. Based upon the reported clinical observations, these findings are discussed from the following aspects: 1. The isomeric similarity of Haloperidol to Meperidine. 2. Dose response between Haloperidol and analgesic effect. 3. The clinical literature regarding the use of Haloperidol for the effective withdrawal or maintenance of narcotic addicts. 4. The analgesic property as it relates to the opiate receptor."}
{"id": "PMID:222742", "title": "A comment on the functional specificities of cyclic AMP-dependent and cyclic GMP-dependent protein kinases.", "content": "Cyclic AMP-dependent and cyclic GMP-dependent protein kinases (protein kinases A and G, respectively) utilize the same phosphate acceptor proteins when assayed in in vitro systems. Nevertheless, protein kinase A phosphorylates preferentially free histone, whereas protein kinase G greatly favors the histone which is associated with polydeoxyribonucleotide. On the other hand, when cytoplasmic soluble substrates such as phosphorylase kinase are used, the reactions are always more favorable for protein kinase A rather than for protein kinase G. Available evidence implies that the topographic relationship between enzyme and substrate may be an important determining factor for the functional specificities of these two classes of protein kinases.", "contents": "A comment on the functional specificities of cyclic AMP-dependent and cyclic GMP-dependent protein kinases. Cyclic AMP-dependent and cyclic GMP-dependent protein kinases (protein kinases A and G, respectively) utilize the same phosphate acceptor proteins when assayed in in vitro systems. Nevertheless, protein kinase A phosphorylates preferentially free histone, whereas protein kinase G greatly favors the histone which is associated with polydeoxyribonucleotide. On the other hand, when cytoplasmic soluble substrates such as phosphorylase kinase are used, the reactions are always more favorable for protein kinase A rather than for protein kinase G. Available evidence implies that the topographic relationship between enzyme and substrate may be an important determining factor for the functional specificities of these two classes of protein kinases."}
{"id": "PMID:222743", "title": "An iron-containing superoxide dismutase from Anacystis nidulans.", "content": "Superoxide dismutase (SOD) was isolated and purified from Anacystis nidulans to near electrophoretic homogeneity. The enzyme has a molecular weight of 37,500, as determined by gel filtration and SDS-gel electrophoresis. The enzyme molecule consists of two subunits of identical molecular weight. Proton-induced X-ray elemental analysis (PIXE) showed that the SOD of A. nidulans is an iron-containing enzyme; the Fe:enzyme mol ratio was found to be 1. The EPR spectra indicated that the active center contains high-spin ferric ion. Based on quantitative EPR data, we conclude that eseentially all iron ions were detected in the EPR experiments and were present in the Fe3+ active center. Effective g'-values were calculated from computer-simulated spectra and analysis of the g'-value anisotropy of the +/-3/2 Kramers doublet made the calculation of crystal field parameters possible. The symmetry of the Fe3+ ion in the SOD molecule was found to be close to rhombic (E/D=0.240).", "contents": "An iron-containing superoxide dismutase from Anacystis nidulans. Superoxide dismutase (SOD) was isolated and purified from Anacystis nidulans to near electrophoretic homogeneity. The enzyme has a molecular weight of 37,500, as determined by gel filtration and SDS-gel electrophoresis. The enzyme molecule consists of two subunits of identical molecular weight. Proton-induced X-ray elemental analysis (PIXE) showed that the SOD of A. nidulans is an iron-containing enzyme; the Fe:enzyme mol ratio was found to be 1. The EPR spectra indicated that the active center contains high-spin ferric ion. Based on quantitative EPR data, we conclude that eseentially all iron ions were detected in the EPR experiments and were present in the Fe3+ active center. Effective g'-values were calculated from computer-simulated spectra and analysis of the g'-value anisotropy of the +/-3/2 Kramers doublet made the calculation of crystal field parameters possible. The symmetry of the Fe3+ ion in the SOD molecule was found to be close to rhombic (E/D=0.240)."}
{"id": "PMID:222744", "title": "Flavocytochrome c of Chromatium vinosum. Some enzymatic properties and subunit structure.", "content": "The function and the structural features of Chromatium vinosum cytochrome c-552 have been investigated. Cytochrome c-552 has a sulfide-cytochrome c reductase activity and also catalyzes the reduction of elementary sulfur to sulfide with reduced benzylviologen as the electron donor. In the sulfide-cytochrome reduction, horse and yeast cytochromes c act as good electron acceptors, but cytochrome c' or cytochrome c-553(550) purified from the organism does not. The subunit structure of cytochrome c-552 has been studied. The cytochrome is split by 6 M urea into cytochrome and flavoprotein moieties with molecular weights of 21,000 and 46,000, respectively. The flavoprotein moiety is obtained by isoelectric focusing in the presence of 6 M urea and 0.1% beta-mercaptoethanol, while the hemoprotein moiety is obtained by gel filtration with Sephacryl S-200 in the presence of 6 M urea and 0.1 M KCl. Neither subunit has sulfide-cytochrome c reductase activity. Attempts to reconstitute the original flavocytochrome c from the subunits have been unsuccessful.", "contents": "Flavocytochrome c of Chromatium vinosum. Some enzymatic properties and subunit structure. The function and the structural features of Chromatium vinosum cytochrome c-552 have been investigated. Cytochrome c-552 has a sulfide-cytochrome c reductase activity and also catalyzes the reduction of elementary sulfur to sulfide with reduced benzylviologen as the electron donor. In the sulfide-cytochrome reduction, horse and yeast cytochromes c act as good electron acceptors, but cytochrome c' or cytochrome c-553(550) purified from the organism does not. The subunit structure of cytochrome c-552 has been studied. The cytochrome is split by 6 M urea into cytochrome and flavoprotein moieties with molecular weights of 21,000 and 46,000, respectively. The flavoprotein moiety is obtained by isoelectric focusing in the presence of 6 M urea and 0.1% beta-mercaptoethanol, while the hemoprotein moiety is obtained by gel filtration with Sephacryl S-200 in the presence of 6 M urea and 0.1 M KCl. Neither subunit has sulfide-cytochrome c reductase activity. Attempts to reconstitute the original flavocytochrome c from the subunits have been unsuccessful."}
{"id": "PMID:222746", "title": "Formation of a TBA reaction product from crown ether in the presence of KO2.", "content": "Potassium superoxide (KO2), which can be dissolved in dimethyl sulfoxide containing crown ether, has been used as a source of O2-. for superoxide reaction systems. We have found that crown ether reacts with thiobarbituric acid (TBA) in the presence of KO2 to form a red pigment, which is a well-known reaction product of lipoperoxide.", "contents": "Formation of a TBA reaction product from crown ether in the presence of KO2. Potassium superoxide (KO2), which can be dissolved in dimethyl sulfoxide containing crown ether, has been used as a source of O2-. for superoxide reaction systems. We have found that crown ether reacts with thiobarbituric acid (TBA) in the presence of KO2 to form a red pigment, which is a well-known reaction product of lipoperoxide."}
{"id": "PMID:222747", "title": "Adrenocorticotropin acutely increases adrenal polyphosphoinositides.", "content": "After adrenocorticotropin (ACTH) treatment for 15 min, adrenal levels of diphosphoinositide and triphosphoinositide appear to increase severalfold. Several other adrenal phospholipids are not appreciably affected by such treatment. Rapid changes in polyphosphoinositides may play a role in hormonal modulation of membrane-associated metabolic events.", "contents": "Adrenocorticotropin acutely increases adrenal polyphosphoinositides. After adrenocorticotropin (ACTH) treatment for 15 min, adrenal levels of diphosphoinositide and triphosphoinositide appear to increase severalfold. Several other adrenal phospholipids are not appreciably affected by such treatment. Rapid changes in polyphosphoinositides may play a role in hormonal modulation of membrane-associated metabolic events."}
{"id": "PMID:222752", "title": "Phosphorylation of hydroxyproline in a synthetic peptide catalyzed by cyclic AMP-dependent protein kinase.", "content": "The cyclic AMP-dependent protein kinase catalyzes the phosphorylation of hydroxyproline present in the heptapeptide, Leu-Arg-Arg-Ala-Hyp-Leu-Gly. The Km value for the reaction with this substrate was high (approximately 18 mM) compared to the Km values reported for the analogous threonine and serine-containing peptides, which were 0.59 mM and 0.016 mM, respectively (Kemp, B.E., Graves, D.J., Benjamini, E., and Krebs, E.G. (1977) J. Biol. Chem. 252, 4888-4894). The Vmax value with the hydroxyproline-containing peptide was 1 mumol . min-1 mg-1 in contrast to Vmax values of 6 mumol . min-1 mg-1 and 20 mumol . min-1 mg-1 for the threonine- and serine-containing peptides, respectively. Phosphate esterified to hydroxyproline present in the peptide was relatively stable in hot alkali, only 10% being released as Pi within 30 min in 0.1 N NaOH at 100 degrees C, whereas all of the phosphate was released from the phosphoserine peptide analogue under these conditions. Phosphohydroxyproline in the peptide was also more stable to acid (5.7 N HCl, 110 degrees C) than phosphoserine, the time for 50% release as Pi being 15 h in contrast to 6 h for the latter.", "contents": "Phosphorylation of hydroxyproline in a synthetic peptide catalyzed by cyclic AMP-dependent protein kinase. The cyclic AMP-dependent protein kinase catalyzes the phosphorylation of hydroxyproline present in the heptapeptide, Leu-Arg-Arg-Ala-Hyp-Leu-Gly. The Km value for the reaction with this substrate was high (approximately 18 mM) compared to the Km values reported for the analogous threonine and serine-containing peptides, which were 0.59 mM and 0.016 mM, respectively (Kemp, B.E., Graves, D.J., Benjamini, E., and Krebs, E.G. (1977) J. Biol. Chem. 252, 4888-4894). The Vmax value with the hydroxyproline-containing peptide was 1 mumol . min-1 mg-1 in contrast to Vmax values of 6 mumol . min-1 mg-1 and 20 mumol . min-1 mg-1 for the threonine- and serine-containing peptides, respectively. Phosphate esterified to hydroxyproline present in the peptide was relatively stable in hot alkali, only 10% being released as Pi within 30 min in 0.1 N NaOH at 100 degrees C, whereas all of the phosphate was released from the phosphoserine peptide analogue under these conditions. Phosphohydroxyproline in the peptide was also more stable to acid (5.7 N HCl, 110 degrees C) than phosphoserine, the time for 50% release as Pi being 15 h in contrast to 6 h for the latter."}
{"id": "PMID:222754", "title": "The contribution of electrostatic factors to the stabilization of the conformation of cytochrome c. Studies on the maleylated protein.", "content": "All the lysines of horse heart cytochrome c were maleylated yielding a low spin product. At room temperature and low salt concentration, this product lacked the 695 nm absorption band and showed tryptophan fluorescence and circular dichroic spectra typical of denatured cytochrome c. The 695 nm band and the native tryptophan fluorescence and circular dichroic spectra were restored by addition of salts, their effectiveness being dependent on the charge of the cation. On low salt concentration, the 695 nm band was also restored by lowering the temperature. Studies of the temperature dependence of the 695 nm band indicate that the thermal denaturation of maleylated cytochrome c occurs at temperatures 60-70 degrees C lower than in the native protein. This implies a destabilization of the native conformation by 5.6 kcal/mol; a similar value is evidenced by comparative urea denaturation studies on the native and modified proteins. The results confirm the assumption that the native conformation of cytochrome c is mostly determined by interactions involving internal residues.", "contents": "The contribution of electrostatic factors to the stabilization of the conformation of cytochrome c. Studies on the maleylated protein. All the lysines of horse heart cytochrome c were maleylated yielding a low spin product. At room temperature and low salt concentration, this product lacked the 695 nm absorption band and showed tryptophan fluorescence and circular dichroic spectra typical of denatured cytochrome c. The 695 nm band and the native tryptophan fluorescence and circular dichroic spectra were restored by addition of salts, their effectiveness being dependent on the charge of the cation. On low salt concentration, the 695 nm band was also restored by lowering the temperature. Studies of the temperature dependence of the 695 nm band indicate that the thermal denaturation of maleylated cytochrome c occurs at temperatures 60-70 degrees C lower than in the native protein. This implies a destabilization of the native conformation by 5.6 kcal/mol; a similar value is evidenced by comparative urea denaturation studies on the native and modified proteins. The results confirm the assumption that the native conformation of cytochrome c is mostly determined by interactions involving internal residues."}
{"id": "PMID:222757", "title": "The role of calcium ion as a mediator of the effects of angiotensin II, catecholamines, and vasopressin on the phosphorylation and activity of enzymes in isolated hepatocytes.", "content": "Angiotensin II, catecholamines, and vasopressin are thought to stimulate hepatic glycogenolysis and gluconeogenesis via a cyclic AMP-independent mechanism that requires calcium ion. The present study explores the possibility that angiotensin II and vasopressin control the activity of regulatory enzymes in carbohydrate metabolism through Ca2+-dependent changes in their state of phosphorylation. Intact hepatocytes labeled with [32P]PO43- were stimulated with angiotensin II, glucagon, or vasopressin and 30 to 33 phosphorylated proteins resolved from the cytoplasmic fraction of the cell by electrophoresis in sodium dodecyl sulfate polyacrylamide slab gels. Treatment of the cells with angiotensin II or vasopressin increased the phosphorylation of 10 to 12 of these cytosolic proteins without causing measurable changes in cyclic AMP-dependent protein kinase activity. Glucagon stimulated the phosphorylation of the same set of 11 to 12 proteins through a marked increase in cyclic AMP-dependent protein kinase activity. The molecular weights of three of the protein bands whose phosphorylation was increased by these hormones correspond to the subunit molecular weights of phosphorylase (Mr = 93,000), glycogen synthase (Mr = 85,000), and pyruvate kinase (Mr = 61,000). Two of these phosphoprotein bands were positively identified as phosphorylase and pyruvate kinase by affinity chromatography and immunoprecipitation, respectively. Incubation of hepatocytes in a Ca2+-free medium completely abolished the effects of angiotensin II and vasopressin on protein phosphorylation but did not alter those of glucagon. Treatment of hepatocytes with angiotensin II, glucagon, or vasopressin stimulated phosphorylase activity by 250 to 260%, inhibited glycogen synthase activity by 50%, and inhibited pyruvate kinase activity by 30 to 35% (peptides) to 70% (glucagon). The effects of angiotensin II and vasopressin on the activity of all three enzymes were completely abolished if the cells were incubated in a Ca2+-free medium while those of glucagon were not altered. The results imply that angiotensin II, catecholamines, and vasopressin control hepatic carbohydrate metabolism through a Ca2+-requiring, cyclic AMP-independent pathway that leads to the phosphorylation of important regulatory enzymes.", "contents": "The role of calcium ion as a mediator of the effects of angiotensin II, catecholamines, and vasopressin on the phosphorylation and activity of enzymes in isolated hepatocytes. Angiotensin II, catecholamines, and vasopressin are thought to stimulate hepatic glycogenolysis and gluconeogenesis via a cyclic AMP-independent mechanism that requires calcium ion. The present study explores the possibility that angiotensin II and vasopressin control the activity of regulatory enzymes in carbohydrate metabolism through Ca2+-dependent changes in their state of phosphorylation. Intact hepatocytes labeled with [32P]PO43- were stimulated with angiotensin II, glucagon, or vasopressin and 30 to 33 phosphorylated proteins resolved from the cytoplasmic fraction of the cell by electrophoresis in sodium dodecyl sulfate polyacrylamide slab gels. Treatment of the cells with angiotensin II or vasopressin increased the phosphorylation of 10 to 12 of these cytosolic proteins without causing measurable changes in cyclic AMP-dependent protein kinase activity. Glucagon stimulated the phosphorylation of the same set of 11 to 12 proteins through a marked increase in cyclic AMP-dependent protein kinase activity. The molecular weights of three of the protein bands whose phosphorylation was increased by these hormones correspond to the subunit molecular weights of phosphorylase (Mr = 93,000), glycogen synthase (Mr = 85,000), and pyruvate kinase (Mr = 61,000). Two of these phosphoprotein bands were positively identified as phosphorylase and pyruvate kinase by affinity chromatography and immunoprecipitation, respectively. Incubation of hepatocytes in a Ca2+-free medium completely abolished the effects of angiotensin II and vasopressin on protein phosphorylation but did not alter those of glucagon. Treatment of hepatocytes with angiotensin II, glucagon, or vasopressin stimulated phosphorylase activity by 250 to 260%, inhibited glycogen synthase activity by 50%, and inhibited pyruvate kinase activity by 30 to 35% (peptides) to 70% (glucagon). The effects of angiotensin II and vasopressin on the activity of all three enzymes were completely abolished if the cells were incubated in a Ca2+-free medium while those of glucagon were not altered. The results imply that angiotensin II, catecholamines, and vasopressin control hepatic carbohydrate metabolism through a Ca2+-requiring, cyclic AMP-independent pathway that leads to the phosphorylation of important regulatory enzymes."}
{"id": "PMID:222758", "title": "Properties of the oscillatory cAMP binding component of Dictyostelium discoideum cells and isolated plasma membranes.", "content": "The cAMP receptor on the surface of aggregation competent Dictyostelium discoideum cells specifically binds [3H]cAMP in an oscillatory manner with a periodicity of 2 min. The oscillatory cAMP-binding component is developmentallly regulated and has the nucleotide specificity expected for recognition of chemotactic signals. The concentration dependence of the peak amplitudes of cAMP binding exhibit an apparent threshold at 10(-8) M cAMP. The threshold concentration for cAMP binding that we measure is consistent with the concentration dependence of signal relay (cAMP secretion) and the chemotactic response. The kinetic data of binding and dissociation are very rapid, consistent with the time course of oscillations in receptor capacity (affinity). Specific binding oscillations are destroyed by heat or chymotrypsin but are insensitive to trypsin or glycosidase. A plasma membrane localization of receptor is supported by enrichment of cAMP binding in a plasma membrane preparation from differentiated cells. Receptor oscillations with a 2-min period are preserved in the membrane preparations, and the peak amplitudes are increased about 10-fold consistent with the enrichment of other plasma membrane markers. The alternating change in the receptor's binding capacity for cAMP may be the basis of the relay refractory period as well as the primary oscillator involved in the generation of postreceptor events such as stimulation of adenylate cyclase, cAMP secretion, and cellular movement, all of which have been previously shown to oscillate.", "contents": "Properties of the oscillatory cAMP binding component of Dictyostelium discoideum cells and isolated plasma membranes. The cAMP receptor on the surface of aggregation competent Dictyostelium discoideum cells specifically binds [3H]cAMP in an oscillatory manner with a periodicity of 2 min. The oscillatory cAMP-binding component is developmentallly regulated and has the nucleotide specificity expected for recognition of chemotactic signals. The concentration dependence of the peak amplitudes of cAMP binding exhibit an apparent threshold at 10(-8) M cAMP. The threshold concentration for cAMP binding that we measure is consistent with the concentration dependence of signal relay (cAMP secretion) and the chemotactic response. The kinetic data of binding and dissociation are very rapid, consistent with the time course of oscillations in receptor capacity (affinity). Specific binding oscillations are destroyed by heat or chymotrypsin but are insensitive to trypsin or glycosidase. A plasma membrane localization of receptor is supported by enrichment of cAMP binding in a plasma membrane preparation from differentiated cells. Receptor oscillations with a 2-min period are preserved in the membrane preparations, and the peak amplitudes are increased about 10-fold consistent with the enrichment of other plasma membrane markers. The alternating change in the receptor's binding capacity for cAMP may be the basis of the relay refractory period as well as the primary oscillator involved in the generation of postreceptor events such as stimulation of adenylate cyclase, cAMP secretion, and cellular movement, all of which have been previously shown to oscillate."}
{"id": "PMID:222762", "title": "Ionic effects on adrenal steroidogenic electron transport. The role of adrenodoxin as an electron shuttle.", "content": "We have shown (Seybert, D., Lambeth, D., and Kamin, H. (1978), J. Biol. Chem. 253, 8355-8358) that, whereas the 1:1 complex between adrenodoxin reductase and adrenodoxin is the active species for cytochrome c reduction, the complex is not sufficient to allow cytochrome P-45011 beta-mediated hydroxylations;adrenodoxin in excess of reductase is required. In the present studies, reduction by NADPH of excess adrenodoxin is shown to occur at a rate sufficient to support both cytochrome P-450 11 beta-mediated hydroxylation of deoxycorticosterone, and cytochrome P-450sec-mediated side chain cleavage of cholesterol. Oxidation-reduction potential and ion effect studies indicate that the mechanism of steroidogenic electron transport involves an adrenodoxin electron \"shuttle\" rather than a macromolecular complex of reductase, adrenodoxin, and cytochrome. The oxidation-reduction potential of adrenodoxin is shifted about -100 mV when bound to reductase, and reduction of the iron-sulfur protein thus promotes dissociation of the complex. The rate of adrenodoxin reduction is first stimulated, then inhibited by increasing salt; the effect is ion-specific, with Ca2+ approximately Mg2+ greater than Na+ greater than NH/+. Similar ion-specific rate effects are observed for both of the cytochrome P-450-mediated hydroxylations, indicating that the same reduction mechanism is required for these reactions. Increasing salt concentrations caused dissociation of the complex; dissociation of the form of the complex containing reduced adrenodoxin occurred at lower salt concentrations than that containing oxidized adrenodoxin. The order of effectiveness of ions in causing dissociation is the same as the order for stimulation of adrenodoxin reduction, suggesting a dissociation step in the mechanism. This proposed model, together with dissociation constants for the form of the complex containing either oxidized or reduced adrenodoxin, allows accurate prediction of the salt rate effects curve. For all ions, an activity maximum is seen at the ion concentration which produces the largest molar difference between associated-oxidized and dissociated-reduced states, and the model predicts the positions of the maxima for adrenodoxin reduction, 11 beta-hydroxylation, and side chain cleavage. Thus reduction-induced dissociation of adrenodoxin from adrenodoxin reductase appears to be a required step in steroidogenic electron transport by this system, and a role for adrenodoxin as a mobile electron shuttle is proposed.", "contents": "Ionic effects on adrenal steroidogenic electron transport. The role of adrenodoxin as an electron shuttle. We have shown (Seybert, D., Lambeth, D., and Kamin, H. (1978), J. Biol. Chem. 253, 8355-8358) that, whereas the 1:1 complex between adrenodoxin reductase and adrenodoxin is the active species for cytochrome c reduction, the complex is not sufficient to allow cytochrome P-45011 beta-mediated hydroxylations;adrenodoxin in excess of reductase is required. In the present studies, reduction by NADPH of excess adrenodoxin is shown to occur at a rate sufficient to support both cytochrome P-450 11 beta-mediated hydroxylation of deoxycorticosterone, and cytochrome P-450sec-mediated side chain cleavage of cholesterol. Oxidation-reduction potential and ion effect studies indicate that the mechanism of steroidogenic electron transport involves an adrenodoxin electron \"shuttle\" rather than a macromolecular complex of reductase, adrenodoxin, and cytochrome. The oxidation-reduction potential of adrenodoxin is shifted about -100 mV when bound to reductase, and reduction of the iron-sulfur protein thus promotes dissociation of the complex. The rate of adrenodoxin reduction is first stimulated, then inhibited by increasing salt; the effect is ion-specific, with Ca2+ approximately Mg2+ greater than Na+ greater than NH/+. Similar ion-specific rate effects are observed for both of the cytochrome P-450-mediated hydroxylations, indicating that the same reduction mechanism is required for these reactions. Increasing salt concentrations caused dissociation of the complex; dissociation of the form of the complex containing reduced adrenodoxin occurred at lower salt concentrations than that containing oxidized adrenodoxin. The order of effectiveness of ions in causing dissociation is the same as the order for stimulation of adrenodoxin reduction, suggesting a dissociation step in the mechanism. This proposed model, together with dissociation constants for the form of the complex containing either oxidized or reduced adrenodoxin, allows accurate prediction of the salt rate effects curve. For all ions, an activity maximum is seen at the ion concentration which produces the largest molar difference between associated-oxidized and dissociated-reduced states, and the model predicts the positions of the maxima for adrenodoxin reduction, 11 beta-hydroxylation, and side chain cleavage. Thus reduction-induced dissociation of adrenodoxin from adrenodoxin reductase appears to be a required step in steroidogenic electron transport by this system, and a role for adrenodoxin as a mobile electron shuttle is proposed."}
{"id": "PMID:222764", "title": "Accessibility of some regions of DNA in chromatin (chicken erythrocytes) to single strand-specific nucleases.", "content": "The susceptibility of the DNA in chromatin to single strand-specific nucleases was examined using nuclease P1, mung bean nuclease, and venom phosphodiesterase. A stage in the reaction exists where the size range of the solubilized products is similar for each of the three nucleases and is nearly independent of incubation time. During this stage, the chromatin fragments sediment in the range of 30 to 100 S and contain duplex DNA ranging from 1 to 10 million daltons. Starting with chromatin depleted of histones H1 and H5 similar fragments are generated. In both cases these nucleoprotein fragments are reduced to nucleosomes and their multimers by micrococcal nuclease. Thus, chromatin contains a limited number of DNA sites which are susceptible to single strand-specific nucleases. These sites occur at intervals of 8 to 80 nucleosomes and are distributed throughout the chromatin. Nucleosome monomers, dimers, or trimers were not observed at any stage of single strand-specific nuclease digestion of nuclei, H1- and H5-depleted chromatin, or micrococcal nuclease-generated oligonucleosomes. Each of the three nucleases converted mononucleosomes (approximately 160 base pairs) to nucleosome cores (approximately 140 base pairs) probably by exonucleolytic action that was facilitated by the prior removal of H1 and H5. The minichromosome of SV40 is highly resistant to digestion by nuclease P1.", "contents": "Accessibility of some regions of DNA in chromatin (chicken erythrocytes) to single strand-specific nucleases. The susceptibility of the DNA in chromatin to single strand-specific nucleases was examined using nuclease P1, mung bean nuclease, and venom phosphodiesterase. A stage in the reaction exists where the size range of the solubilized products is similar for each of the three nucleases and is nearly independent of incubation time. During this stage, the chromatin fragments sediment in the range of 30 to 100 S and contain duplex DNA ranging from 1 to 10 million daltons. Starting with chromatin depleted of histones H1 and H5 similar fragments are generated. In both cases these nucleoprotein fragments are reduced to nucleosomes and their multimers by micrococcal nuclease. Thus, chromatin contains a limited number of DNA sites which are susceptible to single strand-specific nucleases. These sites occur at intervals of 8 to 80 nucleosomes and are distributed throughout the chromatin. Nucleosome monomers, dimers, or trimers were not observed at any stage of single strand-specific nuclease digestion of nuclei, H1- and H5-depleted chromatin, or micrococcal nuclease-generated oligonucleosomes. Each of the three nucleases converted mononucleosomes (approximately 160 base pairs) to nucleosome cores (approximately 140 base pairs) probably by exonucleolytic action that was facilitated by the prior removal of H1 and H5. The minichromosome of SV40 is highly resistant to digestion by nuclease P1."}
{"id": "PMID:222765", "title": "Control of membrane lipid synthesis in Escherichia coli during growth and during the stringent response.", "content": "The regulation of phospholipid synthesis in cells of Escherichia coli was studied in vivo during growth and during the stringent response to amino acid starvation. Strains harboring the hybrid plasmid pLC44-14 (Clark, L., and Carbon, J. (1976) Cell 9,  91-99), which had increased levels of glycerophosphate acyltransferase, were used to study the involvement of this enzyme in the control of phospholipid synthesis. In addition, regulation was studied by measuring the levels of three early intermediates of phospholipid synthesis:phosphatidic acid, CDP-diglyceride, and dCDP-diglyceride. The liponucleotides were measured by a new enzymatic method which allows determinations to be made on crude lipid extracts. Results from experiments on growing cells are consistent with regulation of membrane lipid synthesis occurring in fatty acid synthesis or at the level of glycerophosphate acylation, but not at any later step. Experiments on the inhibition of lipid synthesis during the stringent response make it possible to rule out explanations which involve the inhibition of a single enzyme; enzymes both before and after the liponucleotides in phospholipid synthesis must be affected.", "contents": "Control of membrane lipid synthesis in Escherichia coli during growth and during the stringent response. The regulation of phospholipid synthesis in cells of Escherichia coli was studied in vivo during growth and during the stringent response to amino acid starvation. Strains harboring the hybrid plasmid pLC44-14 (Clark, L., and Carbon, J. (1976) Cell 9,  91-99), which had increased levels of glycerophosphate acyltransferase, were used to study the involvement of this enzyme in the control of phospholipid synthesis. In addition, regulation was studied by measuring the levels of three early intermediates of phospholipid synthesis:phosphatidic acid, CDP-diglyceride, and dCDP-diglyceride. The liponucleotides were measured by a new enzymatic method which allows determinations to be made on crude lipid extracts. Results from experiments on growing cells are consistent with regulation of membrane lipid synthesis occurring in fatty acid synthesis or at the level of glycerophosphate acylation, but not at any later step. Experiments on the inhibition of lipid synthesis during the stringent response make it possible to rule out explanations which involve the inhibition of a single enzyme; enzymes both before and after the liponucleotides in phospholipid synthesis must be affected."}
{"id": "PMID:222766", "title": "The effects of radiation sterilization on the properties of ultrahigh molecular weight polyethylene.", "content": "The effects of radiation sterilization on ultrahigh molecular weight polyethylene were explored by freeze fractures, electron spin resonance, absorption of aqueous media, density measurements, small-angle and wide-angle x-ray scatter, differential scanning calorimetry, infrared and ultraviolet-visible spectrometry, static and dynamic mechanical fatigue measurements, and standard environmental stress cracking measurements. The rate of fluid absorption increased significantly due to the appearance of carbonyl groups. As the fluids were absorbed, density increased and small-angle x-ray scatter (SAXS) intensity diminished slightly, as expected. Small changes in mechanical properties (e.g., tensile properties and dynamic spectrum) were always consistent with the cross-linking which occurs after irradiation; the only significant mechanical deterioration was in the fatigue properties. The nonspherulitic, inhibited crystallinity which characterized this material and which is responsible for its excellent static resistance to environmental stress cracking was not at all changed.", "contents": "The effects of radiation sterilization on the properties of ultrahigh molecular weight polyethylene. The effects of radiation sterilization on ultrahigh molecular weight polyethylene were explored by freeze fractures, electron spin resonance, absorption of aqueous media, density measurements, small-angle and wide-angle x-ray scatter, differential scanning calorimetry, infrared and ultraviolet-visible spectrometry, static and dynamic mechanical fatigue measurements, and standard environmental stress cracking measurements. The rate of fluid absorption increased significantly due to the appearance of carbonyl groups. As the fluids were absorbed, density increased and small-angle x-ray scatter (SAXS) intensity diminished slightly, as expected. Small changes in mechanical properties (e.g., tensile properties and dynamic spectrum) were always consistent with the cross-linking which occurs after irradiation; the only significant mechanical deterioration was in the fatigue properties. The nonspherulitic, inhibited crystallinity which characterized this material and which is responsible for its excellent static resistance to environmental stress cracking was not at all changed."}
{"id": "PMID:222767", "title": "Acute renal failure after total hip replacement.", "content": "Eight of forty-one patients undergoing total hip replacement experienced acute but not fatal renal failure postoperatively. All forty-one patients received transfusions of frozen blood and albumin and their wounds were irrigated with a bacitracin-neomycin-polymyxin solution. All subsequently had some relative hypotension. None of a second, prospective group of fifty-five patients who received the transfusion of albumin, but not frozen blood or the bacitracin-neomycin-polymyxin irrigant, had renal failure. The incidence of hypotension in this group was comparable to that in the first group, yet no cases of renal failure were seen. We therefore recommend that the combination of frozen blood and potentially nephrotoxic drugs be avoided in patients undergoing total hip replacement.", "contents": "Acute renal failure after total hip replacement. Eight of forty-one patients undergoing total hip replacement experienced acute but not fatal renal failure postoperatively. All forty-one patients received transfusions of frozen blood and albumin and their wounds were irrigated with a bacitracin-neomycin-polymyxin solution. All subsequently had some relative hypotension. None of a second, prospective group of fifty-five patients who received the transfusion of albumin, but not frozen blood or the bacitracin-neomycin-polymyxin irrigant, had renal failure. The incidence of hypotension in this group was comparable to that in the first group, yet no cases of renal failure were seen. We therefore recommend that the combination of frozen blood and potentially nephrotoxic drugs be avoided in patients undergoing total hip replacement."}
{"id": "PMID:222769", "title": "Cyclic 3',5' AMP relay in Dictyostelium discoideum. I. A technique to monitor responses to controlled stimuli.", "content": "A perfusion technique was developed to deliver [14C]adenosine 3',5'-cyclic monophosphate (cAMP) stimuli of well-defined magnitude and duration to tritium-labeled Dictyostelium discoideum amoebae and simultaneously monitor the elicited secretion of [3H]cAMP (i.e., the relay response). The tritiated compounds secreted in response to [14C]cAMP stimuli were highly enriched in [3H]cAMP and reflected an increase in intracellular cAMP accompanying stimulation rather than the release of a preexisting store or bulk cellular contents. The secretory response (per 10(6) cells) to 2-min stimuli increased during differentiation from about 0.2 pmol at 0.5 h to approximately 5 pmol of cAMP at 7 h. Without adequate perfusion, amoebae altered the level of cAMP in their environment in two ways: phosphodiesterases destroyed cAMP stimuli under some conditions so as to attenuate the relay response; under other circumstances, secreted cAMP magnified minimal exogenous stimuli into maximal responses. Amoebae, furthermore, would respond to their basal secretion of cAMP autocatalytically if its removal or destruction were interrupted. The perfusion system minimized these cell-induced modifications, allowing control of the level of the stimulus and response in quantitative studies.", "contents": "Cyclic 3',5' AMP relay in Dictyostelium discoideum. I. A technique to monitor responses to controlled stimuli. A perfusion technique was developed to deliver [14C]adenosine 3',5'-cyclic monophosphate (cAMP) stimuli of well-defined magnitude and duration to tritium-labeled Dictyostelium discoideum amoebae and simultaneously monitor the elicited secretion of [3H]cAMP (i.e., the relay response). The tritiated compounds secreted in response to [14C]cAMP stimuli were highly enriched in [3H]cAMP and reflected an increase in intracellular cAMP accompanying stimulation rather than the release of a preexisting store or bulk cellular contents. The secretory response (per 10(6) cells) to 2-min stimuli increased during differentiation from about 0.2 pmol at 0.5 h to approximately 5 pmol of cAMP at 7 h. Without adequate perfusion, amoebae altered the level of cAMP in their environment in two ways: phosphodiesterases destroyed cAMP stimuli under some conditions so as to attenuate the relay response; under other circumstances, secreted cAMP magnified minimal exogenous stimuli into maximal responses. Amoebae, furthermore, would respond to their basal secretion of cAMP autocatalytically if its removal or destruction were interrupted. The perfusion system minimized these cell-induced modifications, allowing control of the level of the stimulus and response in quantitative studies."}
{"id": "PMID:222770", "title": "Cyclic 3',5' AMP relay in Dictyostelium discoideum. II. Requirements for the initiation and termination of the response.", "content": "The secretion of 3H-cyclic adenosine 3',5'-monophosphate (cAMP) by prelabeled and suitably differentiated Dictyostelium discoideum amoebae was elicited in a perfusion apparatus by 10(-10) to 10(-5) M [14C]cAMP stimuli of defined magnitude and duration. Exogenous stimuli evoked an immediate increase in the rate of [3H]cAMP secretion which accelerated continuously to reach a peak of up to 100 times the unstimulated rate after 2--3 min of stimulation. Withdrawal of the stimulus at any time during the response led to a rapid decline to basal levels. Furthermore, a spontaneous decline in secretion rate was observed during prolonged cAMP stimulation, with a return to basal levels after 3--8 min of stimulation. After the initial secretory event, cells did not respond further to the continued presence of external [14C]cAMP unless (a) it was interrupted by a brief recovery period or (b) the level of the stimulus was increased sufficiently. Since the second increment could follow the first at any time, continuous secretion of [3H]cAMP could be sustained for up to 30 min by progressively increasing the stimulus between 10(-10) and 10(-5) M cAMP. The total magnitude of spontaneously terminated responses depended on the size of the increment in applied cAMP, larger stimuli evoking both a more rapid acceleration and a slower deceleration in [3H]cAMP secretion rate. The integrated response to a given increment in stimulus level was apparently independent of its \"shape\" - i.e., the duration, magnitude, and number of sub-steps in the increment. These data support two mechanistic inferences: that amoebae respond in proportion to relative increases in extracellular cAMP concentration, but adapt to the concentration of cAMP itself. The data further suggest that the initiation and termination of the response are mediated by cellular component(s) beyond cAMP-occupied receptors.", "contents": "Cyclic 3',5' AMP relay in Dictyostelium discoideum. II. Requirements for the initiation and termination of the response. The secretion of 3H-cyclic adenosine 3',5'-monophosphate (cAMP) by prelabeled and suitably differentiated Dictyostelium discoideum amoebae was elicited in a perfusion apparatus by 10(-10) to 10(-5) M [14C]cAMP stimuli of defined magnitude and duration. Exogenous stimuli evoked an immediate increase in the rate of [3H]cAMP secretion which accelerated continuously to reach a peak of up to 100 times the unstimulated rate after 2--3 min of stimulation. Withdrawal of the stimulus at any time during the response led to a rapid decline to basal levels. Furthermore, a spontaneous decline in secretion rate was observed during prolonged cAMP stimulation, with a return to basal levels after 3--8 min of stimulation. After the initial secretory event, cells did not respond further to the continued presence of external [14C]cAMP unless (a) it was interrupted by a brief recovery period or (b) the level of the stimulus was increased sufficiently. Since the second increment could follow the first at any time, continuous secretion of [3H]cAMP could be sustained for up to 30 min by progressively increasing the stimulus between 10(-10) and 10(-5) M cAMP. The total magnitude of spontaneously terminated responses depended on the size of the increment in applied cAMP, larger stimuli evoking both a more rapid acceleration and a slower deceleration in [3H]cAMP secretion rate. The integrated response to a given increment in stimulus level was apparently independent of its \"shape\" - i.e., the duration, magnitude, and number of sub-steps in the increment. These data support two mechanistic inferences: that amoebae respond in proportion to relative increases in extracellular cAMP concentration, but adapt to the concentration of cAMP itself. The data further suggest that the initiation and termination of the response are mediated by cellular component(s) beyond cAMP-occupied receptors."}
{"id": "PMID:222771", "title": "Transmembrane biogenesis of the vesicular stomatitis virus glycoprotein.", "content": "Previous work has shown that the mRNA encoding the vesicular stomatitis virus (VSV) glycoprotein (G) is bound to the rough endoplasmic reticulum (RER) and that newly made G protein is localized to the RER. In this paper, we have investigated the topology and processing of the newly synthesized G protein in microsomal vesicles. G was labeled with [35S]methionine ([35S]met), either by pulse-labeling infected cells or by allowing membrane-bound polysomes containing nascent G polipeptides to complete G synthesis in vitro. In either case, digestion of microsomal vesicles with any of several proteases removes approximately 5% (30 amino acids) from each G molecule. These proteases will digest the entire G protein if detergents are present during digestion. Using the method of Dintzis (1961, Proc. Natl. Acad. Sci. U. S. A. 47:247--261) to order tryptic peptides (8), we show that peptides lost from G protein by protease treatment of closed vesicles are derived from the carboxyterminus of the molecule. The newly made VSV G in microsomal membranes is glycosylated. If carbohydrate is removed by glycosidases, the resultant peptide migrates more rapidly on polyacrylamide gels than the unglycosylated, G0, form synthesized in cell-free systems in the absence of membranes. We infer that some proteolytic cleavage of the polypeptide backbone is associated with membrane insertion of G. Further, our findings demonstrate that, soon after synthesis, G is found in a transmembrane, asymmetric orientation in microsomal membranes, with its carboxyterminus exposed to the extracisternal, or cytoplasmic, face of the vesicles, and with most or all of its amino-terminal peptides and its carbohydrate sequestered within the bilayer and lumen of the microsomes.", "contents": "Transmembrane biogenesis of the vesicular stomatitis virus glycoprotein. Previous work has shown that the mRNA encoding the vesicular stomatitis virus (VSV) glycoprotein (G) is bound to the rough endoplasmic reticulum (RER) and that newly made G protein is localized to the RER. In this paper, we have investigated the topology and processing of the newly synthesized G protein in microsomal vesicles. G was labeled with [35S]methionine ([35S]met), either by pulse-labeling infected cells or by allowing membrane-bound polysomes containing nascent G polipeptides to complete G synthesis in vitro. In either case, digestion of microsomal vesicles with any of several proteases removes approximately 5% (30 amino acids) from each G molecule. These proteases will digest the entire G protein if detergents are present during digestion. Using the method of Dintzis (1961, Proc. Natl. Acad. Sci. U. S. A. 47:247--261) to order tryptic peptides (8), we show that peptides lost from G protein by protease treatment of closed vesicles are derived from the carboxyterminus of the molecule. The newly made VSV G in microsomal membranes is glycosylated. If carbohydrate is removed by glycosidases, the resultant peptide migrates more rapidly on polyacrylamide gels than the unglycosylated, G0, form synthesized in cell-free systems in the absence of membranes. We infer that some proteolytic cleavage of the polypeptide backbone is associated with membrane insertion of G. Further, our findings demonstrate that, soon after synthesis, G is found in a transmembrane, asymmetric orientation in microsomal membranes, with its carboxyterminus exposed to the extracisternal, or cytoplasmic, face of the vesicles, and with most or all of its amino-terminal peptides and its carbohydrate sequestered within the bilayer and lumen of the microsomes."}
{"id": "PMID:222772", "title": "Calcium transport and exchange in mouse 3T3 and SV40-3T3 cells.", "content": "The kinetics of Ca++ uptake have been evaluated in 3T3 and SV40-3T3 mouse cells. The data reveal at least two exchangeable cellular compartments in the 3T3 and SV40-3T3 cell over a 50-min exposure to 45Ca++. A rapidly exchanging compartment may represent surface-membrane-localized Ca++ whereas a more slowly exchanging compartment is presumably intracellular. The transition of the 3T3 cell from exponential growth (at 3 day's incubation) to quiescence (at 7 days) is characterized by a 7.5-fold increase in the size of the fast component. Quiescence of the 3T3 cell is also characterized by a 3.2-fold increase in the unidirectional Ca++ influx into the slowly exchanging compartment and a 3.6-fold increase in its size. The increase in size of the slow compartment at quiescence may result from a redistribution of intracellular Ca++ to a more readily exchangeable compartment, possibly reflecting a release of previously bound Ca++. In contrast, no significant change in any of these parameters is observed in the proliferatively active SV40-3T3 cells after corresponding period of incubation, even though these cells attained higher growth densities and underwent postconfluence.", "contents": "Calcium transport and exchange in mouse 3T3 and SV40-3T3 cells. The kinetics of Ca++ uptake have been evaluated in 3T3 and SV40-3T3 mouse cells. The data reveal at least two exchangeable cellular compartments in the 3T3 and SV40-3T3 cell over a 50-min exposure to 45Ca++. A rapidly exchanging compartment may represent surface-membrane-localized Ca++ whereas a more slowly exchanging compartment is presumably intracellular. The transition of the 3T3 cell from exponential growth (at 3 day's incubation) to quiescence (at 7 days) is characterized by a 7.5-fold increase in the size of the fast component. Quiescence of the 3T3 cell is also characterized by a 3.2-fold increase in the unidirectional Ca++ influx into the slowly exchanging compartment and a 3.6-fold increase in its size. The increase in size of the slow compartment at quiescence may result from a redistribution of intracellular Ca++ to a more readily exchangeable compartment, possibly reflecting a release of previously bound Ca++. In contrast, no significant change in any of these parameters is observed in the proliferatively active SV40-3T3 cells after corresponding period of incubation, even though these cells attained higher growth densities and underwent postconfluence."}
{"id": "PMID:222773", "title": "Retention of differentiated properties in an established dog kidney epithelial cell line (MDCK).", "content": "Madin-Darby canine kidney (MDCK) cells grown in tissue culture have the morphological properties of distal tubular epithelial cells, form tight junctions, and lack several proximal tubular enzyme markers. Adenylate cyclase in these cells was stimulated by vasopressin, oxytocin, prostaglandins E1 and E2, glucagon, and cholera toxin. Hormone-stimulated adenylate cyclase activity in isolated membrane preparations was dependent on low concentrations of GTP and had the MgCl2 and pH optima expected for the kidney enzyme. The results, as well as the demonstration of enhanced hemicyst formation induced by cyclic AMP, suggest that the MDCK cell line has retained the differentiated properties of the kidney epithelial cell of origin. When MDCK cells were injected into baby nude mice, continuous nodule growth was observed until adulthood was attained. Histological studies revealed the presence of two cell types: normal mouse fibroblasts which comprise 80--90% of the solid nodule mass, and MDCK cells, which formed epithelial sheets lining internal fluid-filled glands. Electron microscope analysis showed that the mucosal surfaces of the cells were characterized by microvilli which faced the lumen of the glands, that adjacent MDCK cells were joined by tight junctions, and that the serosal surfaces of the epithelial sheets were characterized by smooth plasma membranes which were lined by a continuous basement membrane. These observations lead to the conclusion that the MDCK cells retain regional differentiation of their plasma membranes and the ability to regenerate kidney tubule-like structures in vivo.", "contents": "Retention of differentiated properties in an established dog kidney epithelial cell line (MDCK). Madin-Darby canine kidney (MDCK) cells grown in tissue culture have the morphological properties of distal tubular epithelial cells, form tight junctions, and lack several proximal tubular enzyme markers. Adenylate cyclase in these cells was stimulated by vasopressin, oxytocin, prostaglandins E1 and E2, glucagon, and cholera toxin. Hormone-stimulated adenylate cyclase activity in isolated membrane preparations was dependent on low concentrations of GTP and had the MgCl2 and pH optima expected for the kidney enzyme. The results, as well as the demonstration of enhanced hemicyst formation induced by cyclic AMP, suggest that the MDCK cell line has retained the differentiated properties of the kidney epithelial cell of origin. When MDCK cells were injected into baby nude mice, continuous nodule growth was observed until adulthood was attained. Histological studies revealed the presence of two cell types: normal mouse fibroblasts which comprise 80--90% of the solid nodule mass, and MDCK cells, which formed epithelial sheets lining internal fluid-filled glands. Electron microscope analysis showed that the mucosal surfaces of the cells were characterized by microvilli which faced the lumen of the glands, that adjacent MDCK cells were joined by tight junctions, and that the serosal surfaces of the epithelial sheets were characterized by smooth plasma membranes which were lined by a continuous basement membrane. These observations lead to the conclusion that the MDCK cells retain regional differentiation of their plasma membranes and the ability to regenerate kidney tubule-like structures in vivo."}
{"id": "PMID:222774", "title": "Regulation of epidermal growth factor (EGF) receptor activity during the modulation of protein synthesis.", "content": "The capacity of cultured human fibroblasts to bind 125I-labeled epidermal growth factor (EGF) was measured during protein synthesis inhibition and reinitiation. Protein synthesis was inhibited by incubation of human fibroblasts in histidine-free medium supplemented with L-histidinol to produce a stringent amino acid starvation. Under these conditions 125 I-EGF binding activity decreased with a half-life of 14.5 hours. Protein synthesis could be rapidly reinitiated by the addition of L-histidine to human fibroblasts which had been preincubated in histidinol containing media for 36 to 48 hours. 125I-EGF binding activity rapidly increased upon the reinitiation of protein synthesis. In the presence of serum 100% of the original binding capacity was recovered ten hours after the reinitiation or protein synthesis, while 70% of the binding capacity was recovered in 12 hours in serum-free media. The recovery of 125I-EGF binding activity after the reinitiation of protein synthesis, was not blocked by the presence of Actinomycin D, indicating that the messenger RNA for the EGF receptor may accumulate during the period of histidinol-mediated inhibition of protein synthesis. The time course of recovery of 125I-EGF binding activity after the reinitiation of protein synthesis is very similar to that observed during the recovery of receptor activity following \"down regulation\" of EGF receptor activity. Recovery from down regulation, however, was markedly sensitive to Actinomycin D.", "contents": "Regulation of epidermal growth factor (EGF) receptor activity during the modulation of protein synthesis. The capacity of cultured human fibroblasts to bind 125I-labeled epidermal growth factor (EGF) was measured during protein synthesis inhibition and reinitiation. Protein synthesis was inhibited by incubation of human fibroblasts in histidine-free medium supplemented with L-histidinol to produce a stringent amino acid starvation. Under these conditions 125 I-EGF binding activity decreased with a half-life of 14.5 hours. Protein synthesis could be rapidly reinitiated by the addition of L-histidine to human fibroblasts which had been preincubated in histidinol containing media for 36 to 48 hours. 125I-EGF binding activity rapidly increased upon the reinitiation of protein synthesis. In the presence of serum 100% of the original binding capacity was recovered ten hours after the reinitiation or protein synthesis, while 70% of the binding capacity was recovered in 12 hours in serum-free media. The recovery of 125I-EGF binding activity after the reinitiation of protein synthesis, was not blocked by the presence of Actinomycin D, indicating that the messenger RNA for the EGF receptor may accumulate during the period of histidinol-mediated inhibition of protein synthesis. The time course of recovery of 125I-EGF binding activity after the reinitiation of protein synthesis is very similar to that observed during the recovery of receptor activity following \"down regulation\" of EGF receptor activity. Recovery from down regulation, however, was markedly sensitive to Actinomycin D."}
{"id": "PMID:222775", "title": "Abnormal regulation of de novo purine synthesis and purine salvage in a cultured mouse T-cell lymphoma mutant partially deficient in adenylosuccinate synthetase.", "content": "The isolation and characterization of a mutant murine T-cell lymphoma (S49) with altered purine metabolism is described. This mutant, AU-100, was isolated from a mutagenized population of S49 cells by virtue of its resistance to 0.1 mM 6-azauridine in semisolid agarose. The AU-100 cells are resistant to adenosine mediated cytotoxicity but are extraordinarily sensitive to killing by guanosine. High performance liquid chromatography of AU-100 cell extracts has demonstrated that intracellular levels of GTP, IMP, and GMP are all elevated about 3-fold over those levels found in wild type cells. The AU-100 cells also contain an elevated intracellular level of pyrophosphoribosylphosphate (PPriboseP), which as in wild type cells is diminished by incubation of AU-100 cells with adenosine. However AU-100 cells synthesize purines de novo at a rate less than 35% of that found in wild type cells. In other growth rate experiments, the AU-100 cell line was shown to be resistant to 6-thioguanine and 6-mercaptopurine. Levels of hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) measured in AU-100 cell extracts, however, are 50-66% greater than those levels of HGPRTase found in wild type cell extracts. Nevertheless this mutant S49 cell line cannot efficiently incorporate labeled hypoxanthine into nucleotides since the salvage enzyme HGPRTase is inhibited in vivo. The AU-100 cell line was found to be 80% deficient in adenylosuccinate synthetase, but these cells are not auxotrophic for adenosine or other purines. The significant alterations in the control of purine de novo and salvage metabolism caused by the defect in adenylosuccinate synthetase are mediated by the resulting increased levels of guanosine nucleotides.", "contents": "Abnormal regulation of de novo purine synthesis and purine salvage in a cultured mouse T-cell lymphoma mutant partially deficient in adenylosuccinate synthetase. The isolation and characterization of a mutant murine T-cell lymphoma (S49) with altered purine metabolism is described. This mutant, AU-100, was isolated from a mutagenized population of S49 cells by virtue of its resistance to 0.1 mM 6-azauridine in semisolid agarose. The AU-100 cells are resistant to adenosine mediated cytotoxicity but are extraordinarily sensitive to killing by guanosine. High performance liquid chromatography of AU-100 cell extracts has demonstrated that intracellular levels of GTP, IMP, and GMP are all elevated about 3-fold over those levels found in wild type cells. The AU-100 cells also contain an elevated intracellular level of pyrophosphoribosylphosphate (PPriboseP), which as in wild type cells is diminished by incubation of AU-100 cells with adenosine. However AU-100 cells synthesize purines de novo at a rate less than 35% of that found in wild type cells. In other growth rate experiments, the AU-100 cell line was shown to be resistant to 6-thioguanine and 6-mercaptopurine. Levels of hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) measured in AU-100 cell extracts, however, are 50-66% greater than those levels of HGPRTase found in wild type cell extracts. Nevertheless this mutant S49 cell line cannot efficiently incorporate labeled hypoxanthine into nucleotides since the salvage enzyme HGPRTase is inhibited in vivo. The AU-100 cell line was found to be 80% deficient in adenylosuccinate synthetase, but these cells are not auxotrophic for adenosine or other purines. The significant alterations in the control of purine de novo and salvage metabolism caused by the defect in adenylosuccinate synthetase are mediated by the resulting increased levels of guanosine nucleotides."}
{"id": "PMID:222776", "title": "Amino acid transport in normal and Rous sarcoma virus-transformed chicken embryo fibroblasts.", "content": "A study was made of the transport of a variety of amino acids by uninfected and Rous sarcoma virus-infected chicken embryo fibroblasts. Following a period of amino acid starvation, transformed, but not normal cells, showed increased levels of transport for alpha-aminoisobutyric acid, proline and alanine, three amino acids which are transported primarily by the A transport system. There was no starvation-induced increase in the transport of leucine, phenylalanine, lysine, or cycloleucine. In the absence of starvation, normal and transformed cells exhibited comparable rates of amino acid transport. Cycloheximide was able to block the increase in uptake. The enhanced uptake was characterized by an increase in Vmax for transport and little change in Km. The data demonstrate that an alteration in the regulation of the A amino acid transport system is an early event in malignant transformation by Rous sarcoma virus. However, since this alteration in made manifest only following a period of starvation, our findings suggest that increased amino acid uptake does not play a role in generating the other manifestations of the transformed state seen in cell culture.", "contents": "Amino acid transport in normal and Rous sarcoma virus-transformed chicken embryo fibroblasts. A study was made of the transport of a variety of amino acids by uninfected and Rous sarcoma virus-infected chicken embryo fibroblasts. Following a period of amino acid starvation, transformed, but not normal cells, showed increased levels of transport for alpha-aminoisobutyric acid, proline and alanine, three amino acids which are transported primarily by the A transport system. There was no starvation-induced increase in the transport of leucine, phenylalanine, lysine, or cycloleucine. In the absence of starvation, normal and transformed cells exhibited comparable rates of amino acid transport. Cycloheximide was able to block the increase in uptake. The enhanced uptake was characterized by an increase in Vmax for transport and little change in Km. The data demonstrate that an alteration in the regulation of the A amino acid transport system is an early event in malignant transformation by Rous sarcoma virus. However, since this alteration in made manifest only following a period of starvation, our findings suggest that increased amino acid uptake does not play a role in generating the other manifestations of the transformed state seen in cell culture."}
{"id": "PMID:222777", "title": "Gonadotropin stimulation of cyclic AMP levels in Chinese hamster ovary cells in culture.", "content": "When Chinese Hamster Ovary (CHO) cells, incubated in serum-free medium, are exposed to gonadotropins a transient increase in the intracellular concentration of cyclic AMP is observed. Maximum accumulation of cyclic AMP is noted 30 minutes after addition of either human chorionic gonadotropin (hCG) or follicle stimulating hormone (FSH). Within one to two hours after hormone addition, the intracellular concentrations of cyclic AMP have returned to basal levels. The enhancement of intracellular cyclic AMP levels by hCG is hormone concentration dependent, with maximal stimulation observed at 10 micrograms/ml hCG. The exogenous addition of gonadotropins also slows the growth rate of CHO cells. This effect on growth seems to be mediated through cyclic AMP since the growth rate of a mutant of CHO cells defective in the catalytic subunit of cyclic AMP dependent protein kinase is only slightly decreased.", "contents": "Gonadotropin stimulation of cyclic AMP levels in Chinese hamster ovary cells in culture. When Chinese Hamster Ovary (CHO) cells, incubated in serum-free medium, are exposed to gonadotropins a transient increase in the intracellular concentration of cyclic AMP is observed. Maximum accumulation of cyclic AMP is noted 30 minutes after addition of either human chorionic gonadotropin (hCG) or follicle stimulating hormone (FSH). Within one to two hours after hormone addition, the intracellular concentrations of cyclic AMP have returned to basal levels. The enhancement of intracellular cyclic AMP levels by hCG is hormone concentration dependent, with maximal stimulation observed at 10 micrograms/ml hCG. The exogenous addition of gonadotropins also slows the growth rate of CHO cells. This effect on growth seems to be mediated through cyclic AMP since the growth rate of a mutant of CHO cells defective in the catalytic subunit of cyclic AMP dependent protein kinase is only slightly decreased."}
{"id": "PMID:222778", "title": "T98G: an anchorage-independent human tumor cell line that exhibits stationary phase G1 arrest in vitro.", "content": "T98 and T98G are two related cell lines that were derived from a human glioblastoma multiforma tumor. T98G has almost twice as many chromosomes as T98, suggesting that it is a polyploid variant of T98. Three aspects of control of cellular proliferation were studied in T98 and T98G cells in comparison to WI-38 normal human diploid cells. WI-38 cells have the following properties: (1) they can undergo only a limited number of population doublings in vitro; (2) they cannot proliferate without anchorage; and (3) they become arrested in G1 phase under stationary phase conditions. T98 cells differ from normal cells in all three of these properties, as do many other transformed cell lines. However, the derivative of T98, namely T98G, expresses an unique combination of normal and transformed aspects of the control of cellular proliferation. T98G cells are like normal cells in that they become arrested in G1 phase under stationary phase conditions, yet they also exhibit the transformed characteristics of anchorage independence and immortality. Thus, T98G cells demonstrate that transformation to immortality and anchorage independence can exist without concomitant loss of the normal mechanism for G1 arrest in response to stationary phase conditions. This result supports the hypothesis that each of these three aspects of control of cellular proliferation can be altered independently. Partially transformed cell lines, such as T98G, should be useful for sorting out the biochemical changes associated with transformation in each of these aspects.", "contents": "T98G: an anchorage-independent human tumor cell line that exhibits stationary phase G1 arrest in vitro. T98 and T98G are two related cell lines that were derived from a human glioblastoma multiforma tumor. T98G has almost twice as many chromosomes as T98, suggesting that it is a polyploid variant of T98. Three aspects of control of cellular proliferation were studied in T98 and T98G cells in comparison to WI-38 normal human diploid cells. WI-38 cells have the following properties: (1) they can undergo only a limited number of population doublings in vitro; (2) they cannot proliferate without anchorage; and (3) they become arrested in G1 phase under stationary phase conditions. T98 cells differ from normal cells in all three of these properties, as do many other transformed cell lines. However, the derivative of T98, namely T98G, expresses an unique combination of normal and transformed aspects of the control of cellular proliferation. T98G cells are like normal cells in that they become arrested in G1 phase under stationary phase conditions, yet they also exhibit the transformed characteristics of anchorage independence and immortality. Thus, T98G cells demonstrate that transformation to immortality and anchorage independence can exist without concomitant loss of the normal mechanism for G1 arrest in response to stationary phase conditions. This result supports the hypothesis that each of these three aspects of control of cellular proliferation can be altered independently. Partially transformed cell lines, such as T98G, should be useful for sorting out the biochemical changes associated with transformation in each of these aspects."}
{"id": "PMID:222780", "title": "The effects of Clostridium perfringens enterotoxin on morphology, viability, and macromolecular synthesis in Vero cells.", "content": "Vero (African green monkey kidney) cells grown in tissue culture monolayer were sensitive to Clostridium perfringens enterotoxin. Within 30 minutes of exposure to the enterotoxin gross morphological damage was observed and within 40 minutes approximately 75% of the cells had detached. Nearly half of the cells were nonviable following 35 to 40 minutes incubation with the enterotoxin. Doses as low as 0.1 ng caused small but detectable inhibition of plating efficiency of the cells while more than 100 ng caused the inhibition to approach 100%. Total inhibition of DNA, RNA, and protein synthesis occurred within 30 minutes exposure to enterotoxin. Heat inactivated enterotoxin had no apparent effects upon cellular morphology, detachment, viability, plating efficiency, or incorporation. We propose that the enterotoxin induces structural damage to the cytoplasmic membrane which results in loss of electrolytes and other essential substances from the cells. The outcome of this process is shut down of macromolecular synthesis, gross morphological damage, and eventual death of the cell.", "contents": "The effects of Clostridium perfringens enterotoxin on morphology, viability, and macromolecular synthesis in Vero cells. Vero (African green monkey kidney) cells grown in tissue culture monolayer were sensitive to Clostridium perfringens enterotoxin. Within 30 minutes of exposure to the enterotoxin gross morphological damage was observed and within 40 minutes approximately 75% of the cells had detached. Nearly half of the cells were nonviable following 35 to 40 minutes incubation with the enterotoxin. Doses as low as 0.1 ng caused small but detectable inhibition of plating efficiency of the cells while more than 100 ng caused the inhibition to approach 100%. Total inhibition of DNA, RNA, and protein synthesis occurred within 30 minutes exposure to enterotoxin. Heat inactivated enterotoxin had no apparent effects upon cellular morphology, detachment, viability, plating efficiency, or incorporation. We propose that the enterotoxin induces structural damage to the cytoplasmic membrane which results in loss of electrolytes and other essential substances from the cells. The outcome of this process is shut down of macromolecular synthesis, gross morphological damage, and eventual death of the cell."}
{"id": "PMID:222781", "title": "Sulfated mucopolysaccharides from normal and virus transformed rodent fibroblasts.", "content": "The sulfated mucopolysaccharide composition of normal and virus transformed Balb 3T3 and BHK21 cell lines is reported. It is shown that normal 3T3 cells contain mainly chondroitin sulfate B and heparitin sulfate. Relatively higher amounts of chondroitin sulface AC were observed in polyoma virus transformed 3T3 cells, besides an absolute increase of all the three sulfated mucopolysaccharides in the polyoma and SV 40 transformed cells. It is shown also that the three sulfated mucopolysaccharides are at least in part at the cell surface. Similar differences in sulfated mucopolysaccharide composition of normal and virus transformed BHK cell lines were also observed.", "contents": "Sulfated mucopolysaccharides from normal and virus transformed rodent fibroblasts. The sulfated mucopolysaccharide composition of normal and virus transformed Balb 3T3 and BHK21 cell lines is reported. It is shown that normal 3T3 cells contain mainly chondroitin sulfate B and heparitin sulfate. Relatively higher amounts of chondroitin sulface AC were observed in polyoma virus transformed 3T3 cells, besides an absolute increase of all the three sulfated mucopolysaccharides in the polyoma and SV 40 transformed cells. It is shown also that the three sulfated mucopolysaccharides are at least in part at the cell surface. Similar differences in sulfated mucopolysaccharide composition of normal and virus transformed BHK cell lines were also observed."}
{"id": "PMID:222783", "title": "Electrophysiology of differentiating mouse spermatozoa.", "content": "The morphological aspects of spermatogenesis are well described in many mammalian species, but functional changes are not completely understood. Electrophysiological parameters were investigated in primary spermatocytes and early and late spermatids isolated from the seminiferous tubules of the mouse. Substantial changes were not detected in membrane potential between different developmental stages. Membrane potential was dependent on both potassium and sodium ion concentration gradients, but not on chloride gradients. The ratio of the permeabilities PNa/Pk varied according to the extracellular concentrations of sodium and potassium. Ouabain, a specific inhibitor of Na+, K+-activated ATPase, produced a maximal reduction in membrane potential of 20%. Comparisons were drawn between differentiating germ cells and previously determined properties of mature spermatozoa.", "contents": "Electrophysiology of differentiating mouse spermatozoa. The morphological aspects of spermatogenesis are well described in many mammalian species, but functional changes are not completely understood. Electrophysiological parameters were investigated in primary spermatocytes and early and late spermatids isolated from the seminiferous tubules of the mouse. Substantial changes were not detected in membrane potential between different developmental stages. Membrane potential was dependent on both potassium and sodium ion concentration gradients, but not on chloride gradients. The ratio of the permeabilities PNa/Pk varied according to the extracellular concentrations of sodium and potassium. Ouabain, a specific inhibitor of Na+, K+-activated ATPase, produced a maximal reduction in membrane potential of 20%. Comparisons were drawn between differentiating germ cells and previously determined properties of mature spermatozoa."}
{"id": "PMID:222784", "title": "Erythroid and granulocytic colony growth in cultures supplemented with human serum lipoproteins.", "content": "The ability of human serum to support erythroid and granulocytic colony formation has been investigated. It was found that normal human serum could replace fetal calf serum in the cultures and was able to support the growth of these hemopoietic colonies. Serum fractions enriched for low density lipoproteins, either by precipitation with Heparin-Mn++ or by ultracentrifugation, was found to contain this growth supporting activity of human serum.", "contents": "Erythroid and granulocytic colony growth in cultures supplemented with human serum lipoproteins. The ability of human serum to support erythroid and granulocytic colony formation has been investigated. It was found that normal human serum could replace fetal calf serum in the cultures and was able to support the growth of these hemopoietic colonies. Serum fractions enriched for low density lipoproteins, either by precipitation with Heparin-Mn++ or by ultracentrifugation, was found to contain this growth supporting activity of human serum."}
{"id": "PMID:222785", "title": "Control of the Balb/c-3T3 cell cycle by nutrients and serum factors: analysis using platelet-derived growth factor and platelet-poor plasma.", "content": "Much controversy regarding the relationship between nutrients and serum in regulation of cell growth can be reconciled by recognizing that serum contains multiple factors which regulate different events in the cell cycle. Serum was fractionated into a platelet-derived growth factor (PDGF), which induces cells to become competent to synthesize DNA, and plasma which allows competent cells to traverse G0/G1 and enter the S phase. Nutrients are not required for the cellular response to PDGF; however amino acids are required for plasma to promote the entry of PDGF-treated, competent cells into S phase. The nutrient independent, PDGF-modulated, growth regulatory event (competence) is located 12 hours prior to the G1/S phase boundary in quiescent, density-arrested Balb/c-3T3 cells. The nutrient dependent, plasma-modulated event is located six hours prior to the G1/S phase boundary and corresponds in concentration of amino acids required for DNA synthesis. Infection of density-arrested Balb/c3T3 cells with SV40 overrides both the nutrient independent and the nutrient dependent growth regulatory events.", "contents": "Control of the Balb/c-3T3 cell cycle by nutrients and serum factors: analysis using platelet-derived growth factor and platelet-poor plasma. Much controversy regarding the relationship between nutrients and serum in regulation of cell growth can be reconciled by recognizing that serum contains multiple factors which regulate different events in the cell cycle. Serum was fractionated into a platelet-derived growth factor (PDGF), which induces cells to become competent to synthesize DNA, and plasma which allows competent cells to traverse G0/G1 and enter the S phase. Nutrients are not required for the cellular response to PDGF; however amino acids are required for plasma to promote the entry of PDGF-treated, competent cells into S phase. The nutrient independent, PDGF-modulated, growth regulatory event (competence) is located 12 hours prior to the G1/S phase boundary in quiescent, density-arrested Balb/c-3T3 cells. The nutrient dependent, plasma-modulated event is located six hours prior to the G1/S phase boundary and corresponds in concentration of amino acids required for DNA synthesis. Infection of density-arrested Balb/c3T3 cells with SV40 overrides both the nutrient independent and the nutrient dependent growth regulatory events."}
{"id": "PMID:222786", "title": "Properties of Na-K pump in primary cultures of kidney cells.", "content": "Activities related to Na-K transport were measured in cell cultures of ground squirrel kidney cortex in order to compare these cells with those of intact kidney and of continuous cell lines. A microsomal preparation containing plasma membrane Na,K-ATPase from fresh kidney showed twice the activity of a similar preparation from 72-hour cultured cells. Na,K-ATPase of homogenates of 72-hour cells showed one-third to one-fourth the specific activity of that from 6-hour cultured cells. The associated K-dependent phosphatase activity also declined as a function of time in culture. The ouabain-sensitive influx of K into 6-hour cultured cells was twice as great as the K influx into 72-hour cells. The number of sites binding 3H-ouabain in intact cultured cells declined 81% on a cell protein basis between 6 and 72 hours in culture. This decline in ouabain binding sites was relatively greater than that of K influx, so that the K turnover number increased over this same time period. The decline in ouabain-sensitive K influx during culture was complementary to an increase in furosemide-sensitive K influx. Measurements of unidirectional and net K fluxes showed that there were three components of K influx into 3-day cultured cells: ouabain-sensitive Na:K exchange, furosemide-sensitive K:K exchange, and K diffusion. In the 6-hour cultures, however, there was no furosemide-sensitive K:K exchange. Thus, after three days in culture ground squirrel kidney cells lose a feature characteristic of the original parent cells (high Na,K-ATPase activity), and gain a feature common to many undifferentiated cultured cells (furosemide-sensitive K:K exchange).", "contents": "Properties of Na-K pump in primary cultures of kidney cells. Activities related to Na-K transport were measured in cell cultures of ground squirrel kidney cortex in order to compare these cells with those of intact kidney and of continuous cell lines. A microsomal preparation containing plasma membrane Na,K-ATPase from fresh kidney showed twice the activity of a similar preparation from 72-hour cultured cells. Na,K-ATPase of homogenates of 72-hour cells showed one-third to one-fourth the specific activity of that from 6-hour cultured cells. The associated K-dependent phosphatase activity also declined as a function of time in culture. The ouabain-sensitive influx of K into 6-hour cultured cells was twice as great as the K influx into 72-hour cells. The number of sites binding 3H-ouabain in intact cultured cells declined 81% on a cell protein basis between 6 and 72 hours in culture. This decline in ouabain binding sites was relatively greater than that of K influx, so that the K turnover number increased over this same time period. The decline in ouabain-sensitive K influx during culture was complementary to an increase in furosemide-sensitive K influx. Measurements of unidirectional and net K fluxes showed that there were three components of K influx into 3-day cultured cells: ouabain-sensitive Na:K exchange, furosemide-sensitive K:K exchange, and K diffusion. In the 6-hour cultures, however, there was no furosemide-sensitive K:K exchange. Thus, after three days in culture ground squirrel kidney cells lose a feature characteristic of the original parent cells (high Na,K-ATPase activity), and gain a feature common to many undifferentiated cultured cells (furosemide-sensitive K:K exchange)."}
{"id": "PMID:222787", "title": "Tyrosinase maturation and pigment expression in B16 melanoma: relation to theophylline treatment and intracellular cyclic AMP.", "content": "We have studied the effects of theophylline treatment on pigmentation characteristics and growth of two B16 melanoma cell lines, HFH-18 and P/140. Cell counts of control and theophylline-treated cultures confirmed that the drug inhibits cell growth. Light and electron microscope cytochemistry with the L-dopa reaction indicated that the two cell lines differ in their ability to transfer Golgi-associated tyrosinase to developing premelanosomes. The results of these experiments, considered with results of electrophoretic analyses and activity measurements by the Pomerantz method, also provide evidence that increased tyrosinase synthesis occurs in response to theophylline treatment. In addition, results indicate that theophylline induces changes in the rate of synthetic or degradative posttranslational modification of tyrosinase. Measurements of intracellular cyclic AMP levels by radioimmunoassay in control cultures and in theophylline- and alpha-MSH-treated cultures were made. Although the hormone induced spectacular increases in cyclic AMP levels, theophylline produced no detectable change. These results indicate that theophylline differs from alpha-MSH because theophylline-induced changes in pigmentation may not require the participation of intracellular cyclic AMP.", "contents": "Tyrosinase maturation and pigment expression in B16 melanoma: relation to theophylline treatment and intracellular cyclic AMP. We have studied the effects of theophylline treatment on pigmentation characteristics and growth of two B16 melanoma cell lines, HFH-18 and P/140. Cell counts of control and theophylline-treated cultures confirmed that the drug inhibits cell growth. Light and electron microscope cytochemistry with the L-dopa reaction indicated that the two cell lines differ in their ability to transfer Golgi-associated tyrosinase to developing premelanosomes. The results of these experiments, considered with results of electrophoretic analyses and activity measurements by the Pomerantz method, also provide evidence that increased tyrosinase synthesis occurs in response to theophylline treatment. In addition, results indicate that theophylline induces changes in the rate of synthetic or degradative posttranslational modification of tyrosinase. Measurements of intracellular cyclic AMP levels by radioimmunoassay in control cultures and in theophylline- and alpha-MSH-treated cultures were made. Although the hormone induced spectacular increases in cyclic AMP levels, theophylline produced no detectable change. These results indicate that theophylline differs from alpha-MSH because theophylline-induced changes in pigmentation may not require the participation of intracellular cyclic AMP."}
{"id": "PMID:222788", "title": "Tumorigenicity of cells transformed by Simian virus 40 and of hybrids between such cells and normal diploid cells.", "content": "A number of newly isolated clonal cell lines derived from diploid mouse embryo cells transformed by SV40 were examined in vitro and in vivo. Although these lines showed the properties that define transformation in vitro, they were not tumorigenic for many passages after their initial isolation. Cells from tumours eventually produced by the SV40-transformed cells were fused with diploid mouse embryo cells. The hybrids formed were initially non-tumorigenic. This indicates that a normal diploid cell can suppress the malignant phenotype of a tumorigenic SV40-transformed cell. The hybrid cells did, however, express the SV40 T antigen and they nad a clearly transformed phenotype in vitro. It thus appears that neither the transformed phenotype nor the expression of the SV40 T antigen are enough to endow a cell with the ability to grow progressively in vivo. The relationship between the transformed phenotype and tumorigenicity was further studied by fusing malignant mouse melanoma cells with non-tumorigenic SV40-transformed cells. The hybrids expressed the transformed phenotype in vitro but unable to form tumours in vivo. The changes that occur in cells after transformation by SV40 do not apparently affect the ability of these cells to suppress the malignant phenotype of tumour cells.", "contents": "Tumorigenicity of cells transformed by Simian virus 40 and of hybrids between such cells and normal diploid cells. A number of newly isolated clonal cell lines derived from diploid mouse embryo cells transformed by SV40 were examined in vitro and in vivo. Although these lines showed the properties that define transformation in vitro, they were not tumorigenic for many passages after their initial isolation. Cells from tumours eventually produced by the SV40-transformed cells were fused with diploid mouse embryo cells. The hybrids formed were initially non-tumorigenic. This indicates that a normal diploid cell can suppress the malignant phenotype of a tumorigenic SV40-transformed cell. The hybrid cells did, however, express the SV40 T antigen and they nad a clearly transformed phenotype in vitro. It thus appears that neither the transformed phenotype nor the expression of the SV40 T antigen are enough to endow a cell with the ability to grow progressively in vivo. The relationship between the transformed phenotype and tumorigenicity was further studied by fusing malignant mouse melanoma cells with non-tumorigenic SV40-transformed cells. The hybrids expressed the transformed phenotype in vitro but unable to form tumours in vivo. The changes that occur in cells after transformation by SV40 do not apparently affect the ability of these cells to suppress the malignant phenotype of tumour cells."}
{"id": "PMID:222789", "title": "The evolution of excitable behaviour in Dictyostelium.", "content": "Aggregation of Dictyostelium discoideum amoebae is effected by relayed cyclic AMP (cAMP) signals. The period of this wave propagation drops abruptly at the transition from aggregative to post-aggregative development. In this paper I demonstrate that the light-scattering response induced by a low concentration pulse of cAMP evolves from one lasting 5 min to one lasting 2 min. The definitive establishment of the 2-min response coincides with the beginning of post-aggregative gene expression. Amoebae at the aggregative stage are unable to respond to a second cAMP pulse delivered less than 4 min after the first, whereas at the post-aggregative stage they can respond to 2 pulses separated by 1 min or longer. Addition of cAMP phosphodiesterase to amoebae at the aggregative stage can in part mimic the change in excitable behaviour: the response is shortened and the amoebae can respond more frequently. However, the shortened response is not post-aggregative in shape and the prolonged presence of cyclic nucleotides induces different responses at the aggregative and post-aggregative stage. Both these results suggest that the rate of destruction of the relayed signal is not solely responsible for the change in excitability.", "contents": "The evolution of excitable behaviour in Dictyostelium. Aggregation of Dictyostelium discoideum amoebae is effected by relayed cyclic AMP (cAMP) signals. The period of this wave propagation drops abruptly at the transition from aggregative to post-aggregative development. In this paper I demonstrate that the light-scattering response induced by a low concentration pulse of cAMP evolves from one lasting 5 min to one lasting 2 min. The definitive establishment of the 2-min response coincides with the beginning of post-aggregative gene expression. Amoebae at the aggregative stage are unable to respond to a second cAMP pulse delivered less than 4 min after the first, whereas at the post-aggregative stage they can respond to 2 pulses separated by 1 min or longer. Addition of cAMP phosphodiesterase to amoebae at the aggregative stage can in part mimic the change in excitable behaviour: the response is shortened and the amoebae can respond more frequently. However, the shortened response is not post-aggregative in shape and the prolonged presence of cyclic nucleotides induces different responses at the aggregative and post-aggregative stage. Both these results suggest that the rate of destruction of the relayed signal is not solely responsible for the change in excitability."}
{"id": "PMID:222790", "title": "Studies of membrane fusion. IV. Fusion of HeLa cells with Sendai virus.", "content": "The Sendai virus-induced fusion of HeLa cells has been studied by freeze-fracture electron microscopy. Freeze-fracture observations confirm previous scanning electron-microscope studies (1977) and show that at 4 degrees C virus particles bind to the cell surface and that cell agglutination results from the crosslinking by virus particles of microvilli on adjacent cells. Incubation at 37 degrees C initiates a change in viral envelope structure and fusion of 'altered' virus particles with the cell plasma membrane. Fusion of a virus particle with two crosslinked cells is probably the membrane fusion event which initiates cell-cell fusion; fusion is completed as a result of virally induced cell swelling. Lateral diffusion of viral envelope components following virus-cell fusion and, in some instances, an aggregation of plasma membrane intramembrane particles occurs in swollen cells. These observations show that the mechanisms of viral envelope-cell and probably cell-cell fusion are the same as have been reported for erythrocytes. Although endocytosis of intact virus particles does occur, the specialized cell-mediated mechanism for fusion of the viral envelope with the cell plasma membrane suggests that this, and not viropexis, is the mechanism of Sendai virus infection.", "contents": "Studies of membrane fusion. IV. Fusion of HeLa cells with Sendai virus. The Sendai virus-induced fusion of HeLa cells has been studied by freeze-fracture electron microscopy. Freeze-fracture observations confirm previous scanning electron-microscope studies (1977) and show that at 4 degrees C virus particles bind to the cell surface and that cell agglutination results from the crosslinking by virus particles of microvilli on adjacent cells. Incubation at 37 degrees C initiates a change in viral envelope structure and fusion of 'altered' virus particles with the cell plasma membrane. Fusion of a virus particle with two crosslinked cells is probably the membrane fusion event which initiates cell-cell fusion; fusion is completed as a result of virally induced cell swelling. Lateral diffusion of viral envelope components following virus-cell fusion and, in some instances, an aggregation of plasma membrane intramembrane particles occurs in swollen cells. These observations show that the mechanisms of viral envelope-cell and probably cell-cell fusion are the same as have been reported for erythrocytes. Although endocytosis of intact virus particles does occur, the specialized cell-mediated mechanism for fusion of the viral envelope with the cell plasma membrane suggests that this, and not viropexis, is the mechanism of Sendai virus infection."}
{"id": "PMID:222791", "title": "Studies of membrane fusion. V. Fusion of erythrocytes with non-haemolytic Sendai virus.", "content": "The fusion of human erythrocytes with non-haemolytic '1-day' Sendai virus has been studied by electron microscopy. The mechanism of viral envelope-cell fusion is the same as that described previously for haemolytic '3-day' Sendai virus except that fusion is frequently arrested at an initial stage when 2 segments of smooth linear viral membrane fuse and become incorporated into the erythrocyte membrane. After longer periods of incubation at 37 degrees C, in addition to many partly fused virus particles, long (up to 4 micrometer) lengths of smooth linear viral membrane are seen within the erythrocyte membrane which arise by linear aggregation of shorter (approximately 0.25 micrometer long) segments of smooth linear membrane derived from individual fused viral envelopes. Cell-Cell fusion, as a result of the fusion of a viral envelope with 2 adjacent erythrocytes also occurs but, in the absence of cell swelling, fusion is arrested at this stage with cells joined by one (or more) small cytoplasmic bridges. Typical fused cells are produced if such cells are swollen with hypotonic buffer. These observations provide further evidence that membrane fusion and cell swelling are distinct events in cell fusion and that cell swelling is the driving force both for completing the incorporation of the viral envelope into the cell membrane and for expanding cells connected by small cytoplasmic bridges to form spherical fused cells. Little lateral diffusion of viral envelope components occurs in the absence of cell swelling; in fact, some aggregation of components occurs. Comparison with previous studies using haemolytic '3-day' Sendai virus suggests that virally induced cell swelling perturbs membrane structure so as to allow the rapid lateral diffusion of integrated viral envelope components.", "contents": "Studies of membrane fusion. V. Fusion of erythrocytes with non-haemolytic Sendai virus. The fusion of human erythrocytes with non-haemolytic '1-day' Sendai virus has been studied by electron microscopy. The mechanism of viral envelope-cell fusion is the same as that described previously for haemolytic '3-day' Sendai virus except that fusion is frequently arrested at an initial stage when 2 segments of smooth linear viral membrane fuse and become incorporated into the erythrocyte membrane. After longer periods of incubation at 37 degrees C, in addition to many partly fused virus particles, long (up to 4 micrometer) lengths of smooth linear viral membrane are seen within the erythrocyte membrane which arise by linear aggregation of shorter (approximately 0.25 micrometer long) segments of smooth linear membrane derived from individual fused viral envelopes. Cell-Cell fusion, as a result of the fusion of a viral envelope with 2 adjacent erythrocytes also occurs but, in the absence of cell swelling, fusion is arrested at this stage with cells joined by one (or more) small cytoplasmic bridges. Typical fused cells are produced if such cells are swollen with hypotonic buffer. These observations provide further evidence that membrane fusion and cell swelling are distinct events in cell fusion and that cell swelling is the driving force both for completing the incorporation of the viral envelope into the cell membrane and for expanding cells connected by small cytoplasmic bridges to form spherical fused cells. Little lateral diffusion of viral envelope components occurs in the absence of cell swelling; in fact, some aggregation of components occurs. Comparison with previous studies using haemolytic '3-day' Sendai virus suggests that virally induced cell swelling perturbs membrane structure so as to allow the rapid lateral diffusion of integrated viral envelope components."}
{"id": "PMID:222793", "title": "Probable pituitary adenoma with adrenocorticotropin hypersecretion (corticotropinoma) secondary to Addison's disease.", "content": "A 50-yr-old woman with Addison's disease from the age of 14 yr was diagnosed as empty sella turcica in 1974 (Rev Clin Esp 139: 183, 1975). She subsequently continued with hyperpigmentation in spite of adequate hormone substitution therapy which permitted her to lead a normal life. When studied she showed an extreme elevation of plasma ACTH (1500--2000 pg/ml), and with dexamethasone (2 and 8 mg/day) continued to have levels of 900 pg/ml. With 60 mg hydrocortisone daily, effects of overdosage were observed (swelling and Cushingoid facies) associated with depigmentation. However, she continued to manifest levels of plasma ACTH of 700 pg/ml and an absence of circadian rhythm. It seems likely that this patient represents a case of pituitary ACTH secretory adenoma (corticotropinoma) secondary to the preexisting Addison's disease. The circulating levels of other pituitary hormones were normal.", "contents": "Probable pituitary adenoma with adrenocorticotropin hypersecretion (corticotropinoma) secondary to Addison's disease. A 50-yr-old woman with Addison's disease from the age of 14 yr was diagnosed as empty sella turcica in 1974 (Rev Clin Esp 139: 183, 1975). She subsequently continued with hyperpigmentation in spite of adequate hormone substitution therapy which permitted her to lead a normal life. When studied she showed an extreme elevation of plasma ACTH (1500--2000 pg/ml), and with dexamethasone (2 and 8 mg/day) continued to have levels of 900 pg/ml. With 60 mg hydrocortisone daily, effects of overdosage were observed (swelling and Cushingoid facies) associated with depigmentation. However, she continued to manifest levels of plasma ACTH of 700 pg/ml and an absence of circadian rhythm. It seems likely that this patient represents a case of pituitary ACTH secretory adenoma (corticotropinoma) secondary to the preexisting Addison's disease. The circulating levels of other pituitary hormones were normal."}
{"id": "PMID:222794", "title": "Regulation of receptor by homologous hormone enhances sensitivity and broadens scope of radioreceptor assay for human growth hormone.", "content": "In standard competitive binding assays (including radioreceptor assays) unlabeled ligand (hormone) competes with labeled ligand (hormone) for binding to a fixed number of binding (receptor) sites. Detection of the unlabeled ligand occurs when the occupancy of binding sites by the unlabeled ligand is sufficient to reduce the binding of labeled ligand. A common feature of the hormone-receptor interaction is the ability of the hormone to regulate the affinity and/or the concentration of its homologous receptor. In the present study, by exploiting the ability of human GH to regulate by negative feedback the concentration of its own receptors, we have enhanced the sensitivity of the human GH radioreceptor assay 5-fold. The ability of hormone to regulate receptor concentration and affinity affords wide opportunities to broaden the scope as well as to enhance the sensitivity of radioreceptor assays.", "contents": "Regulation of receptor by homologous hormone enhances sensitivity and broadens scope of radioreceptor assay for human growth hormone. In standard competitive binding assays (including radioreceptor assays) unlabeled ligand (hormone) competes with labeled ligand (hormone) for binding to a fixed number of binding (receptor) sites. Detection of the unlabeled ligand occurs when the occupancy of binding sites by the unlabeled ligand is sufficient to reduce the binding of labeled ligand. A common feature of the hormone-receptor interaction is the ability of the hormone to regulate the affinity and/or the concentration of its homologous receptor. In the present study, by exploiting the ability of human GH to regulate by negative feedback the concentration of its own receptors, we have enhanced the sensitivity of the human GH radioreceptor assay 5-fold. The ability of hormone to regulate receptor concentration and affinity affords wide opportunities to broaden the scope as well as to enhance the sensitivity of radioreceptor assays."}
{"id": "PMID:222795", "title": "Circadian variation of plasma catecholamines in young and old men: relation to rapid eye movement and slow wave sleep.", "content": "Young and old healthy subjects with indwelling venous cannulae were found to undergo significant diurnal variations in plasma catecholamine levels. Both norepinephrine and epinephrine levels peaked in late morning and reached lowest values at night during sleep. Catecholamine levels were similar during slow wave and rapid eye movement sleep. While epinephrine levels were unaffected by age, norepinephrine levels were greater in older subjects by 28% during the day (at 1100 h; P less than 0.01) and by 75% at night (between 2200--0900 h; P less than 0.01). Older subjects slept less well; they had 90% less stage 4 sleep, 27% less rapid eye movement sleep, and twice as much wakefulness at night (P less than 0.05). These findings raise the possibility that this well known age effect on sleep may be related to increased sympathetic nervous system activity.", "contents": "Circadian variation of plasma catecholamines in young and old men: relation to rapid eye movement and slow wave sleep. Young and old healthy subjects with indwelling venous cannulae were found to undergo significant diurnal variations in plasma catecholamine levels. Both norepinephrine and epinephrine levels peaked in late morning and reached lowest values at night during sleep. Catecholamine levels were similar during slow wave and rapid eye movement sleep. While epinephrine levels were unaffected by age, norepinephrine levels were greater in older subjects by 28% during the day (at 1100 h; P less than 0.01) and by 75% at night (between 2200--0900 h; P less than 0.01). Older subjects slept less well; they had 90% less stage 4 sleep, 27% less rapid eye movement sleep, and twice as much wakefulness at night (P less than 0.05). These findings raise the possibility that this well known age effect on sleep may be related to increased sympathetic nervous system activity."}
{"id": "PMID:222796", "title": "Multiple symmetric lipomatosis (Launois-Bensaude syndrome) - adipose tissue insensitivity to cyclic AMP.", "content": "Adipocytes prepared from lipomatous tissue of a patient with multiple symmetric lipomatosis have been incubated in the presence of norepinephrine, or insulin, or both. No lipolytic response to norepinephrine could be detected. However, the cellular content of cyclic AMP doubled in response to norepinephrine. Insulin reversed this. The data suggest that fat mobilization from the lipoma is impaired, and that this is due to resistance to the effect of cyclic AMP on hormone sensitive lipase.", "contents": "Multiple symmetric lipomatosis (Launois-Bensaude syndrome) - adipose tissue insensitivity to cyclic AMP. Adipocytes prepared from lipomatous tissue of a patient with multiple symmetric lipomatosis have been incubated in the presence of norepinephrine, or insulin, or both. No lipolytic response to norepinephrine could be detected. However, the cellular content of cyclic AMP doubled in response to norepinephrine. Insulin reversed this. The data suggest that fat mobilization from the lipoma is impaired, and that this is due to resistance to the effect of cyclic AMP on hormone sensitive lipase."}
{"id": "PMID:222797", "title": "Pleocytosis and immunoglobulin changes in cerebrospinal fluid and herpesvirus serology in patients with Guillain-Barr\u00e9 syndrome.", "content": "In a follow-up study of 24 patients with Guillain-Barr\u00e9 syndrome, 55% developed a cerebrospinal fluid (CSF) mononuclear pleocytosis, which persisted for 4 months or more. Raised index values of CSF-immunoglobulin G (IgG), CSF-IgA, and CSF-IgM, indicating synthesis of the immunoglobulin in question in the central nervous system, were found in 63, 35, and 25%, respectively. Agarose gel eletrophoresis revealed oligoclonal immunoglobulin in CSF in 21% and in both CSF and serum in another 21% of the patients. Twenty-five percent had abnormally low kappa/lambda ratios of CSF and/or serum, indicating synthesis of oligoclonal immunoglobulin, mainly of the lambda light-chain type. The inflammatory reaction in the central nervous system, as reflected by pleocytosis, immunoglobulin synthesis, and oligoclonal immunoglobulin, was not correlated to the severity or course of Guillain-Barr\u00e9 syndrome. A raised CSF-IgM index and oligoclonal immunoglobulin were found more often in the Guillain-Barr\u00e9 syndrome patients who displayed pleocytosis. All patients had or developed antibodies to Epstein-Barr virus. Three patients had serology indicating a primary infection, 11 patients had antibody changes indicating a reactivated infection, and 10 had serology indicating previous exposure. Two patients showed serological evidence for a primary cytomegalovirus infection, 2 had serology indicative of a reactivated infection, 12 had titers as caused by previous exposure, and 8 remained seronegative. Virus-specific IgM was measurable in all cases of primary infection. Neither primary or reactivated Epstein-Barr virus nor cytomegalovirus infections were obviously related to CSF pleocytosis.", "contents": "Pleocytosis and immunoglobulin changes in cerebrospinal fluid and herpesvirus serology in patients with Guillain-Barr\u00e9 syndrome. In a follow-up study of 24 patients with Guillain-Barr\u00e9 syndrome, 55% developed a cerebrospinal fluid (CSF) mononuclear pleocytosis, which persisted for 4 months or more. Raised index values of CSF-immunoglobulin G (IgG), CSF-IgA, and CSF-IgM, indicating synthesis of the immunoglobulin in question in the central nervous system, were found in 63, 35, and 25%, respectively. Agarose gel eletrophoresis revealed oligoclonal immunoglobulin in CSF in 21% and in both CSF and serum in another 21% of the patients. Twenty-five percent had abnormally low kappa/lambda ratios of CSF and/or serum, indicating synthesis of oligoclonal immunoglobulin, mainly of the lambda light-chain type. The inflammatory reaction in the central nervous system, as reflected by pleocytosis, immunoglobulin synthesis, and oligoclonal immunoglobulin, was not correlated to the severity or course of Guillain-Barr\u00e9 syndrome. A raised CSF-IgM index and oligoclonal immunoglobulin were found more often in the Guillain-Barr\u00e9 syndrome patients who displayed pleocytosis. All patients had or developed antibodies to Epstein-Barr virus. Three patients had serology indicating a primary infection, 11 patients had antibody changes indicating a reactivated infection, and 10 had serology indicating previous exposure. Two patients showed serological evidence for a primary cytomegalovirus infection, 2 had serology indicative of a reactivated infection, 12 had titers as caused by previous exposure, and 8 remained seronegative. Virus-specific IgM was measurable in all cases of primary infection. Neither primary or reactivated Epstein-Barr virus nor cytomegalovirus infections were obviously related to CSF pleocytosis."}
{"id": "PMID:222798", "title": "Thin-layer immunoassay for determination of antibodies to herpes simplex virus.", "content": "Thin-layer immunoassay (TIA) is a simple serological technique suitable for analysis of large numbers of samples. In this study, TIA was evaluated for determination of antibodies to herpes simplex virus. Herpes simplex virus antigen used in TIA was purified from material released from virus-infected cells. The results obtained by TIA were compared with those obtained by neutralization and complement fixation tests. TIA was found to be as sensitive as the neutralization test for demonstration of herpes simplex virus antibodies. No false-negative or -positive reactions were observed. In primary herpes simplex virus-1 infections, an antibody response was demonstrated by TIA, whereas antibodies could not be demonstrated in patients with primary herpes simplex virus-2 infections.", "contents": "Thin-layer immunoassay for determination of antibodies to herpes simplex virus. Thin-layer immunoassay (TIA) is a simple serological technique suitable for analysis of large numbers of samples. In this study, TIA was evaluated for determination of antibodies to herpes simplex virus. Herpes simplex virus antigen used in TIA was purified from material released from virus-infected cells. The results obtained by TIA were compared with those obtained by neutralization and complement fixation tests. TIA was found to be as sensitive as the neutralization test for demonstration of herpes simplex virus antibodies. No false-negative or -positive reactions were observed. In primary herpes simplex virus-1 infections, an antibody response was demonstrated by TIA, whereas antibodies could not be demonstrated in patients with primary herpes simplex virus-2 infections."}
{"id": "PMID:222799", "title": "Decreased cerebrospinal fluid cyclic adenosine 3',5'-monophosphate in bacterial meningitis.", "content": "The concentration of cyclic adenosine 3',5'-monophosphate (cAMP) in 16 cerebrospinal fluid samples from eight patients with bacterial meningitis due to several different organisms was determined. An age- and sex-matched control group of 12 patients with a variety of acute, noninfectious systemic and neurological diseases was also examined. To quantitate the amount of cAMP, a new, improved radioimmunoassay was used with the ability to measure 2.5 X 10(-15) mol of cAMP. The mean concentration of cAMP in the cerebrospinal fluid from patients with meningitis was 0.05 nM, and from patients in the control group it was 1.18 nM. The difference between these two values is statistically significant. The decreased cAMP concentration in the cerebrospinal fluid from patients with bacterial meningitis did not seem to be secondary to metabolism by bacteria or leukocytes, increased enzymatic degradation within the cerebrospinal fluid, or an artifact introduced by the collection and storage procedure. Since the concentration of cAMP in the cerebrospinal fluid is normally found to be within narrow limits and probably reflects intracellular cAMP levels, the results described in this study suggest that interference with cAMP metabolism in central nervous system tissue occurs in bacterial meningitis. This finding seems to be independent of the causative organism and might explain the pathogenesis of selected, neurological manifestations of this disease.", "contents": "Decreased cerebrospinal fluid cyclic adenosine 3',5'-monophosphate in bacterial meningitis. The concentration of cyclic adenosine 3',5'-monophosphate (cAMP) in 16 cerebrospinal fluid samples from eight patients with bacterial meningitis due to several different organisms was determined. An age- and sex-matched control group of 12 patients with a variety of acute, noninfectious systemic and neurological diseases was also examined. To quantitate the amount of cAMP, a new, improved radioimmunoassay was used with the ability to measure 2.5 X 10(-15) mol of cAMP. The mean concentration of cAMP in the cerebrospinal fluid from patients with meningitis was 0.05 nM, and from patients in the control group it was 1.18 nM. The difference between these two values is statistically significant. The decreased cAMP concentration in the cerebrospinal fluid from patients with bacterial meningitis did not seem to be secondary to metabolism by bacteria or leukocytes, increased enzymatic degradation within the cerebrospinal fluid, or an artifact introduced by the collection and storage procedure. Since the concentration of cAMP in the cerebrospinal fluid is normally found to be within narrow limits and probably reflects intracellular cAMP levels, the results described in this study suggest that interference with cAMP metabolism in central nervous system tissue occurs in bacterial meningitis. This finding seems to be independent of the causative organism and might explain the pathogenesis of selected, neurological manifestations of this disease."}
{"id": "PMID:222800", "title": "Comparison of indirect hemagglutination and indirect immunofluorescence tests with microneutralization tests for detection of type-specific Herpesvirus hominis antibody.", "content": "Indirect hemagglutinating and immunofluorescent antibody responses to Herpesvirus hominis types 1 and 2 were compared to neutralizing antibody responses in infected humans from whom H. hominis type 1 or 2 was isolated. The indirect immunofluorescent antibody test was shown to be the most sensitive and specific for primary human infections. The sensitivity and specificity of the indirect hemagglutination and the immunofluorescent antibody tests were shown to be equal to that of the microneutralization test among patients who had primary or recurrent H. hominis type 2 infections. It is suggested that the indirect hemagglutination test is preferable for assaying large populations for previous infection with H. hominis type 2 because it is rapid, easier to perform, and more economical. The intermediate range of titer differences (deltat) between H. hominis types 1 and 2 previously reported to be due to infections with both viruses was shown to occur in all three tests among patients with primary infections with either virus.", "contents": "Comparison of indirect hemagglutination and indirect immunofluorescence tests with microneutralization tests for detection of type-specific Herpesvirus hominis antibody. Indirect hemagglutinating and immunofluorescent antibody responses to Herpesvirus hominis types 1 and 2 were compared to neutralizing antibody responses in infected humans from whom H. hominis type 1 or 2 was isolated. The indirect immunofluorescent antibody test was shown to be the most sensitive and specific for primary human infections. The sensitivity and specificity of the indirect hemagglutination and the immunofluorescent antibody tests were shown to be equal to that of the microneutralization test among patients who had primary or recurrent H. hominis type 2 infections. It is suggested that the indirect hemagglutination test is preferable for assaying large populations for previous infection with H. hominis type 2 because it is rapid, easier to perform, and more economical. The intermediate range of titer differences (deltat) between H. hominis types 1 and 2 previously reported to be due to infections with both viruses was shown to occur in all three tests among patients with primary infections with either virus."}
{"id": "PMID:222801", "title": "Production of high-titer bovine rotavirus with trypsin.", "content": "Titers of bovine rotavirus in excess of 10(9) immunofluorescent infectious units per ml of culture fluids have been produced, using trypsin treatment of the virus. Infectivity of preparations of the virus can be increased with as little as 1 ng of trypsin per ml, with maximum increases of 1 to 2 log10 with 1 microgram of trypsin per ml. The virus grows to titers in excess of 10(5) immunofluorescent units per ml in MDBK, LLC-MK2, MA-104, and HeLa cells. When MDBK cells are infected with a multiplicity of infection of 20, maximum yields of cell-associated, trypsin-enhanceable virus are obtained 4 to 8 h postinfection. Maximum yields of cell-free, trypsin-enhanceable virus are produced 16 to 20 h postinfection. The results presented here indicate that trypsin can be used to produce high-titer stocks of bovine rotavirus.", "contents": "Production of high-titer bovine rotavirus with trypsin. Titers of bovine rotavirus in excess of 10(9) immunofluorescent infectious units per ml of culture fluids have been produced, using trypsin treatment of the virus. Infectivity of preparations of the virus can be increased with as little as 1 ng of trypsin per ml, with maximum increases of 1 to 2 log10 with 1 microgram of trypsin per ml. The virus grows to titers in excess of 10(5) immunofluorescent units per ml in MDBK, LLC-MK2, MA-104, and HeLa cells. When MDBK cells are infected with a multiplicity of infection of 20, maximum yields of cell-associated, trypsin-enhanceable virus are obtained 4 to 8 h postinfection. Maximum yields of cell-free, trypsin-enhanceable virus are produced 16 to 20 h postinfection. The results presented here indicate that trypsin can be used to produce high-titer stocks of bovine rotavirus."}
{"id": "PMID:222802", "title": "Sensitivity of enzyme-linked immunosorbent assay, complement fixation, and hemagglutination inhibition serological tests for detection of Sendai virus antibody in laboratory mice.", "content": "The enzyme-linked immunosorbent assay technique for detection of Sendai virus antibody in mice was approximately 100- and 300-fold more sensitive than the complement fixation and hemagglutination inhibition tests, respectively. The assay also permitted direct quantitative measurement of the amount of antibody on a single serum dilution rather than by the more traditional serial titration.", "contents": "Sensitivity of enzyme-linked immunosorbent assay, complement fixation, and hemagglutination inhibition serological tests for detection of Sendai virus antibody in laboratory mice. The enzyme-linked immunosorbent assay technique for detection of Sendai virus antibody in mice was approximately 100- and 300-fold more sensitive than the complement fixation and hemagglutination inhibition tests, respectively. The assay also permitted direct quantitative measurement of the amount of antibody on a single serum dilution rather than by the more traditional serial titration."}
{"id": "PMID:222803", "title": "Assay of human interferon in Vero cells by several methods.", "content": "Four methods for the assay of human interferon in Vero cells were compared based on the inhibition of viral cytopathic effect (CPE) in tubes, the inhibition of CPE in microplates, the reduction of plaques, and the inhibition of quantitative hemadsorption. For inhibition of CPE, Sindbis virus, vesicular stomatitis virus, poliovirus type 2, and vaccinia virus were used for challenge. In the plaque reduction method, Sindbis virus, vesicular stomatitis virus, and poliovirus were employed, and Newcastle disease virus was used in the quantitative hemadsorption assay. Sindbis virus was most susceptible to interferon in those tests measuring inhibition of CPE, but vesicular stomatitis virus was as sensitive in the plaque reduction method. Highest titers of interferon were recorded in microplates, especially with Sindbis virus as the challenge agent, followed by the quantitative inhibition assay. The CPE inhibition method was the simplest, and the quantitative hemadsorption assay was the most rapid to perform. Reproducibilities, as shown by the coefficient of variation, were 15, 39, and 59% for plaque reduction, CPE inhibition in tubes, and CPE inhibition in microplates, respectively.", "contents": "Assay of human interferon in Vero cells by several methods. Four methods for the assay of human interferon in Vero cells were compared based on the inhibition of viral cytopathic effect (CPE) in tubes, the inhibition of CPE in microplates, the reduction of plaques, and the inhibition of quantitative hemadsorption. For inhibition of CPE, Sindbis virus, vesicular stomatitis virus, poliovirus type 2, and vaccinia virus were used for challenge. In the plaque reduction method, Sindbis virus, vesicular stomatitis virus, and poliovirus were employed, and Newcastle disease virus was used in the quantitative hemadsorption assay. Sindbis virus was most susceptible to interferon in those tests measuring inhibition of CPE, but vesicular stomatitis virus was as sensitive in the plaque reduction method. Highest titers of interferon were recorded in microplates, especially with Sindbis virus as the challenge agent, followed by the quantitative inhibition assay. The CPE inhibition method was the simplest, and the quantitative hemadsorption assay was the most rapid to perform. Reproducibilities, as shown by the coefficient of variation, were 15, 39, and 59% for plaque reduction, CPE inhibition in tubes, and CPE inhibition in microplates, respectively."}
{"id": "PMID:222804", "title": "Immunoglobulin M anti-hepatitis A virus determination reorienting gradient centrifugation for diagnosis of Acute Hepatitis A.", "content": "The persistence of antibody to hepatitis A antigen (anti-HAV) of the immunoglobulin M (IgM) class was evaluated in 88 sera of 51 acute hepatitis A patients. IgM was separated from IgG by a 2-h reorienting sucrose gradient ultracentrifugation, and the titer of anti-HAV was determined in the IgG- and IgM-containing fractions by solid-hase radioimmunoassay. IgM anti-HAV was the predominating antibody at onset of jaundice and persisted in these patients for at least 60 days, but not longer than 115 days. The demonstration of IgM anti-HAV is therefore a valuable tool for the diagnosis of recent hepatitis A infection.", "contents": "Immunoglobulin M anti-hepatitis A virus determination reorienting gradient centrifugation for diagnosis of Acute Hepatitis A. The persistence of antibody to hepatitis A antigen (anti-HAV) of the immunoglobulin M (IgM) class was evaluated in 88 sera of 51 acute hepatitis A patients. IgM was separated from IgG by a 2-h reorienting sucrose gradient ultracentrifugation, and the titer of anti-HAV was determined in the IgG- and IgM-containing fractions by solid-hase radioimmunoassay. IgM anti-HAV was the predominating antibody at onset of jaundice and persisted in these patients for at least 60 days, but not longer than 115 days. The demonstration of IgM anti-HAV is therefore a valuable tool for the diagnosis of recent hepatitis A infection."}
{"id": "PMID:222805", "title": "Enhancement of antigen incorporation and infectivity of cell cultures by human rotavirus.", "content": "Infection of cell cultures with human rotavirus preparations was attempted and the effects of trypsin and low-speed centrifugation on antigen incorporation, as demonstrated by immunofluorescence and radioimmunoassay, were determined. In addition, the effect of viral aggregation on antigen incorporation was investigated by filtering viral preparations. Four strains of human rotavirus were employed, and the results were compared to those obtained with two tissue culture-adapted animal rotaviruses. Centrifugation and trypsin appeared to have little or no effect on infectivity of the tissue culture-adapted (simian rotavirus) or -adaptable (Nebraska calf diarrhea virus) strains, whereas centrifugation and viral aggregation appeared to be essential for the human viruses. In addition, trypsin enhanced antigen incorporation of the human strains to some extent. Infectivity for cell cultures and in vitro human rotavirus protein formation was demonstrated by [35S]methionine incorporation, and the specificity of this human viral protein was established by radio-immunoprecipitation.", "contents": "Enhancement of antigen incorporation and infectivity of cell cultures by human rotavirus. Infection of cell cultures with human rotavirus preparations was attempted and the effects of trypsin and low-speed centrifugation on antigen incorporation, as demonstrated by immunofluorescence and radioimmunoassay, were determined. In addition, the effect of viral aggregation on antigen incorporation was investigated by filtering viral preparations. Four strains of human rotavirus were employed, and the results were compared to those obtained with two tissue culture-adapted animal rotaviruses. Centrifugation and trypsin appeared to have little or no effect on infectivity of the tissue culture-adapted (simian rotavirus) or -adaptable (Nebraska calf diarrhea virus) strains, whereas centrifugation and viral aggregation appeared to be essential for the human viruses. In addition, trypsin enhanced antigen incorporation of the human strains to some extent. Infectivity for cell cultures and in vitro human rotavirus protein formation was demonstrated by [35S]methionine incorporation, and the specificity of this human viral protein was established by radio-immunoprecipitation."}
{"id": "PMID:222806", "title": "Counterimmunoelectrophoresis test for immunoglobulin M antibodies to group B coxsackievirus.", "content": "A counterimmunoelectrophoresis test was developed for immunoglobulin M (IgM) antibodies to group B coxsackievirus (CB) types 1 through 5. The IgM precipitin line could be identified and differentiated from the IgG line by treating sera with 2-mercaptoethanol. Antigen purity was demonstrated by single precipitin lines occurring only to the homologous antigen when tested with type-specific hyperimmune rabbit sera. Serum pairs from 19 of 22 patients with documented CB type 1,3,4, and 5 infections were positive for IgM antibody to the infecting serotype, whereas 2 of 7 pairs from CB type 2 patients were positive. Heterologous IgM antibodies were present in sera from 14 fo 29 CB patients. Of the 14 patients with heterologous IgM antibodies, 12 also had greater than or equal to 4-fold rises in whole serum neutralizing antibody to heterologous serotypes. Only three control sera from 72 patients with coxsackievirus group A, echovirus, or other viral infections had IgM antibody to CB serotypes.", "contents": "Counterimmunoelectrophoresis test for immunoglobulin M antibodies to group B coxsackievirus. A counterimmunoelectrophoresis test was developed for immunoglobulin M (IgM) antibodies to group B coxsackievirus (CB) types 1 through 5. The IgM precipitin line could be identified and differentiated from the IgG line by treating sera with 2-mercaptoethanol. Antigen purity was demonstrated by single precipitin lines occurring only to the homologous antigen when tested with type-specific hyperimmune rabbit sera. Serum pairs from 19 of 22 patients with documented CB type 1,3,4, and 5 infections were positive for IgM antibody to the infecting serotype, whereas 2 of 7 pairs from CB type 2 patients were positive. Heterologous IgM antibodies were present in sera from 14 fo 29 CB patients. Of the 14 patients with heterologous IgM antibodies, 12 also had greater than or equal to 4-fold rises in whole serum neutralizing antibody to heterologous serotypes. Only three control sera from 72 patients with coxsackievirus group A, echovirus, or other viral infections had IgM antibody to CB serotypes."}
{"id": "PMID:222807", "title": "Diarrhea and rotavirus infection associated with differing regimens for postnatal care of newborn babies.", "content": "Surveillance of 2,041 babies born during 4 winter months in one obstetric hospital in Melbourne, Australia, showed that 215 developed acute diarrhea during the first 2 weeks of life. Babies requiring special care from birth had a high incidence of sporadic diarrhea (36%). The incidence of diarrhea among healthy full-term babies was low if they were \"rooming-in\" with their mothers (2 to 3%) but high if they were housed in communal nurseries (29%). The most important factor influencing incidence of diarrhea was proximity to other newborn babies and frequency of handling by related adults. Breast feeding did not always protect babies from diarrhea. Excretion of rotaviruses was temporally retlated to diarrhea in 61 to 76% of healthy full-term babies and in 44% of babies requiring special care. Other eneteric pathogens, including enerotoxigenic Escherichia coli, were occasionally isolated. Calculation of the ratios of symptomatic to asymptomatic infection suggests that babies requiring special care are much more likely to develop symptomatic illness after rotavious infection than are full-term babies.", "contents": "Diarrhea and rotavirus infection associated with differing regimens for postnatal care of newborn babies. Surveillance of 2,041 babies born during 4 winter months in one obstetric hospital in Melbourne, Australia, showed that 215 developed acute diarrhea during the first 2 weeks of life. Babies requiring special care from birth had a high incidence of sporadic diarrhea (36%). The incidence of diarrhea among healthy full-term babies was low if they were \"rooming-in\" with their mothers (2 to 3%) but high if they were housed in communal nurseries (29%). The most important factor influencing incidence of diarrhea was proximity to other newborn babies and frequency of handling by related adults. Breast feeding did not always protect babies from diarrhea. Excretion of rotaviruses was temporally retlated to diarrhea in 61 to 76% of healthy full-term babies and in 44% of babies requiring special care. Other eneteric pathogens, including enerotoxigenic Escherichia coli, were occasionally isolated. Calculation of the ratios of symptomatic to asymptomatic infection suggests that babies requiring special care are much more likely to develop symptomatic illness after rotavious infection than are full-term babies."}
{"id": "PMID:222808", "title": "Comparison of cynomolgus and rhesus monkey kidney cells for recovery of viruses from clinical specimens.", "content": "In a study of virus recovery from clinical specimens, cynomolgus monkey kidney cells demonstrated sensitivity equivalent or slightly superior to rhesus kidney cells for siolation of myxo- and paramyxoviruses, adenoviruses, and enteroviruses.", "contents": "Comparison of cynomolgus and rhesus monkey kidney cells for recovery of viruses from clinical specimens. In a study of virus recovery from clinical specimens, cynomolgus monkey kidney cells demonstrated sensitivity equivalent or slightly superior to rhesus kidney cells for siolation of myxo- and paramyxoviruses, adenoviruses, and enteroviruses."}
{"id": "PMID:222809", "title": "Gangliosides sensitize unresponsive fibroblasts to Escherichia coli heat-labile enterotoxin.", "content": "Chemically transformed mouse fibroblasts did not raise their cyclic AMP level in response to Escherichia coli heat-labile enterotoxin. These fibroblasts did, however, incorporate exogenous mono-, di-, and trisialogangliosides. After the uptake of monosialoganglioside galactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosylceramide (GM1), the cells responded to E. coli heat-labile enterotoxin. The di- and trisialogangliosides were considerably less effective. GM1, the putative cholera toxin (choleragen) receptor, has been implicated previously as the receptor for E. coli heat-labile enterotoxin based on the ability of the free ganglioside to inhibit the effects of toxin. This investigation establishes that the ganglioside, when incorporated into fibroblasts, serves a functional role in mediating the responsiveness to the toxin.", "contents": "Gangliosides sensitize unresponsive fibroblasts to Escherichia coli heat-labile enterotoxin. Chemically transformed mouse fibroblasts did not raise their cyclic AMP level in response to Escherichia coli heat-labile enterotoxin. These fibroblasts did, however, incorporate exogenous mono-, di-, and trisialogangliosides. After the uptake of monosialoganglioside galactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosylceramide (GM1), the cells responded to E. coli heat-labile enterotoxin. The di- and trisialogangliosides were considerably less effective. GM1, the putative cholera toxin (choleragen) receptor, has been implicated previously as the receptor for E. coli heat-labile enterotoxin based on the ability of the free ganglioside to inhibit the effects of toxin. This investigation establishes that the ganglioside, when incorporated into fibroblasts, serves a functional role in mediating the responsiveness to the toxin."}
{"id": "PMID:222810", "title": "Anaphylactic relase of a basophil kallikrein-like activity. II. A mediator of immediate hypersensitivity reactions.", "content": "This report describes the immune release of a new mediator from human peripheral leukocytes, a basophil kallikrein-like activity (BK-A). The release process is initiated by the interaction of antigen on anti-IgE with cell-bound IgE, and appears to be similar in mechanism to the relase of histamine and other mediators of the immediate hypersensitivity reaction. The dose-response relationships and kinetics of histamine and BK-A release from antigen-challenged peripheral leukocytes are similar. The relase of the BK-A is calcium and temperature dependent, requires metabolic energy, and is controlled by hormone-receptor interactions that influence the cellular level of cyclic AMP, as has been described for other mediators of immediate hypersensitivity reactions. The data indicate that the interaction of BK-A with human plasma kininogen, generates immunoreactive kinin. We conclude that the antigen-IgE interation leads to the release from human basophils of a new mediator, a basophil kallikrein-like activity which may well be a link between reactions of immediate hypersenstivitity and the plasma and/or tissue kinin-generating systems.", "contents": "Anaphylactic relase of a basophil kallikrein-like activity. II. A mediator of immediate hypersensitivity reactions. This report describes the immune release of a new mediator from human peripheral leukocytes, a basophil kallikrein-like activity (BK-A). The release process is initiated by the interaction of antigen on anti-IgE with cell-bound IgE, and appears to be similar in mechanism to the relase of histamine and other mediators of the immediate hypersensitivity reaction. The dose-response relationships and kinetics of histamine and BK-A release from antigen-challenged peripheral leukocytes are similar. The relase of the BK-A is calcium and temperature dependent, requires metabolic energy, and is controlled by hormone-receptor interactions that influence the cellular level of cyclic AMP, as has been described for other mediators of immediate hypersensitivity reactions. The data indicate that the interaction of BK-A with human plasma kininogen, generates immunoreactive kinin. We conclude that the antigen-IgE interation leads to the release from human basophils of a new mediator, a basophil kallikrein-like activity which may well be a link between reactions of immediate hypersenstivitity and the plasma and/or tissue kinin-generating systems."}
{"id": "PMID:222811", "title": "Metabolic studies in familial hypercholesterolemia. Evidence for a gene-dosage effect in vivo.", "content": "To investigate the gene-dosage effect in familial hypercholesterolemia (FH), metabolic studies were conducted in a group of well-characterized patients with either heterozygous (n = 7) or homozygous (n = 7) FH and the results were compared to those obtained in normal subjects (n = 6). The turnover of (125)I-labeled low-density lipoprotein (LDL) was measured in all of the normals, all but one of the FH heterozygotes, and in all of the homozygotes. Chemical cholesterol balance was performed simultaneously with the (125)I-LDL turnover in all seven of the homozygotes. With regard to (125)I-LDL turnover, FH homozygotes, who possess two doses of the mutant FH gene, exhibited a threefold increase in the rate of apoLDL synthesis while the fractional catabolic rate (FCR) for the apoprotein was only about one-third of normal. Heterozygotes, who have only one dose of the mutant FH gene, exhibited intermediate values for both parameters; that is, the FCR was two-thirds of normal and the apoLDL synthetic rate was 1.7-fold greater than normal. THE DATA INDICATE THAT THE SINGLE GENE DEFECT IN FH PRODUCES TWO DISTINCT ABNORMALITIES OF LDL METABOLISM: (a) an increase in the synthetic rate for apoLDL and (b) a decrease in the efficiency of apoLDL catabolism. Both defects are more severe in FH homozygotes than in heterozygotes. The FCR for apoLDL in the homozygotes appeared to be fixed at congruent with 17%/d whereas the plasma LDL level varied about twofold. These findings suggest that the twofold variation in plasma LDL levels observed in these seven patients is caused by variation in the plasma apoLDL synthetic rates. Consistent with this conclusion was the finding that the correlation between the plasma LDL level and the apoLDL synthetic rates in the seven FH homozygotes was 0.943. The rate of total body cholesterol synthesis determined by chemical cholesterol balance did not appear to clearly differ between normals and patients with either one or two mutant FH genes. Two of the youngest FH homozygotes exhibited cholesterol overproduction but the other five did not. No consistent abnormality of bile acid metabolism was observed in these patients. Because the daily plasma flux of cholesterol on LDL is about threefold greater than the amount of cholesterol produced per day, a significant amount of the cholesterol liberated from LDL degradation must be reused.", "contents": "Metabolic studies in familial hypercholesterolemia. Evidence for a gene-dosage effect in vivo. To investigate the gene-dosage effect in familial hypercholesterolemia (FH), metabolic studies were conducted in a group of well-characterized patients with either heterozygous (n = 7) or homozygous (n = 7) FH and the results were compared to those obtained in normal subjects (n = 6). The turnover of (125)I-labeled low-density lipoprotein (LDL) was measured in all of the normals, all but one of the FH heterozygotes, and in all of the homozygotes. Chemical cholesterol balance was performed simultaneously with the (125)I-LDL turnover in all seven of the homozygotes. With regard to (125)I-LDL turnover, FH homozygotes, who possess two doses of the mutant FH gene, exhibited a threefold increase in the rate of apoLDL synthesis while the fractional catabolic rate (FCR) for the apoprotein was only about one-third of normal. Heterozygotes, who have only one dose of the mutant FH gene, exhibited intermediate values for both parameters; that is, the FCR was two-thirds of normal and the apoLDL synthetic rate was 1.7-fold greater than normal. THE DATA INDICATE THAT THE SINGLE GENE DEFECT IN FH PRODUCES TWO DISTINCT ABNORMALITIES OF LDL METABOLISM: (a) an increase in the synthetic rate for apoLDL and (b) a decrease in the efficiency of apoLDL catabolism. Both defects are more severe in FH homozygotes than in heterozygotes. The FCR for apoLDL in the homozygotes appeared to be fixed at congruent with 17%/d whereas the plasma LDL level varied about twofold. These findings suggest that the twofold variation in plasma LDL levels observed in these seven patients is caused by variation in the plasma apoLDL synthetic rates. Consistent with this conclusion was the finding that the correlation between the plasma LDL level and the apoLDL synthetic rates in the seven FH homozygotes was 0.943. The rate of total body cholesterol synthesis determined by chemical cholesterol balance did not appear to clearly differ between normals and patients with either one or two mutant FH genes. Two of the youngest FH homozygotes exhibited cholesterol overproduction but the other five did not. No consistent abnormality of bile acid metabolism was observed in these patients. Because the daily plasma flux of cholesterol on LDL is about threefold greater than the amount of cholesterol produced per day, a significant amount of the cholesterol liberated from LDL degradation must be reused."}
{"id": "PMID:222812", "title": "Catecholamine regulation of human erythrocyte membrane protein kinase.", "content": "The effect of catecholamines on membrane-associated protein kinase in the mature human erythrocyte was investigated. Protein kinase activity was assayed after isolation of membranes from intact erythrocytes incubated with and without catecholamines. Activation of the enzyme is expressed as the ratio of the extent of phosphorylation of exogenous protein substrate in the absence to that in the presence of 2.5 microM cyclic AMP (cAMP). The potent beta-adrenergic agonist, (-)isoproterenol (2 microM), (-)epinephrine (10 microM) and (-)norepinephrine (10 microM) stimulated the cAMP-dependent protein kinase in membranes, 38 +/- 7%, 31 +/- 6%, and 30 +/- 6%, respectively. Maximal stimulation of membrane protein kinase by 10 microM (-)epinephrine was obtained approximately equal to 30 min after initiation of the incubation of erythrocytes with the hormone. The concentrations of (-)catecholamines that gave half-maximal stimulation of the membrane protein kinase were 0.17 microM for isoproterenol, 0.35 microM for epinephrine, and 0.63 microM for norepinephrine. The membrane protein kinase response to beta-adrenergic agonists was found to be stereospecific. The stimulation of membrane protein kinase by 10 microM (-)epinephrine was inhibited by the beta-adrenergic antagonist, (-)propranolol with EC50 = 0.60 microM, and the inhibition of agonist stimulation of the cAMP-dependent protein kinase by propranolol was stereospecific. These studies suggest that a functional beta-adrenergic receptor exists in the mature human erythrocyte.", "contents": "Catecholamine regulation of human erythrocyte membrane protein kinase. The effect of catecholamines on membrane-associated protein kinase in the mature human erythrocyte was investigated. Protein kinase activity was assayed after isolation of membranes from intact erythrocytes incubated with and without catecholamines. Activation of the enzyme is expressed as the ratio of the extent of phosphorylation of exogenous protein substrate in the absence to that in the presence of 2.5 microM cyclic AMP (cAMP). The potent beta-adrenergic agonist, (-)isoproterenol (2 microM), (-)epinephrine (10 microM) and (-)norepinephrine (10 microM) stimulated the cAMP-dependent protein kinase in membranes, 38 +/- 7%, 31 +/- 6%, and 30 +/- 6%, respectively. Maximal stimulation of membrane protein kinase by 10 microM (-)epinephrine was obtained approximately equal to 30 min after initiation of the incubation of erythrocytes with the hormone. The concentrations of (-)catecholamines that gave half-maximal stimulation of the membrane protein kinase were 0.17 microM for isoproterenol, 0.35 microM for epinephrine, and 0.63 microM for norepinephrine. The membrane protein kinase response to beta-adrenergic agonists was found to be stereospecific. The stimulation of membrane protein kinase by 10 microM (-)epinephrine was inhibited by the beta-adrenergic antagonist, (-)propranolol with EC50 = 0.60 microM, and the inhibition of agonist stimulation of the cAMP-dependent protein kinase by propranolol was stereospecific. These studies suggest that a functional beta-adrenergic receptor exists in the mature human erythrocyte."}
{"id": "PMID:222813", "title": "Characterization of the platelet prostaglandin D2 receptor. Loss of prostaglandin D2 receptors in platelets of patients with myeloproliferative disorders.", "content": "Prostaglandin (PG) D(2) is synthesized in platelets at concentrations which could inhibit aggregation via activation of adenylate cyclase. To more directly define platelet-PG interactions, a binding assay has been developed for platelet PG receptors with [(3)H]PGD(2) as ligand. [(3)H]PGD(2) binding to intact platelets was saturable and rapid with the ligand bound by 3 min at 20 degrees C. PG competed with the [(3)H]PGD(2) binding site with a potency series: PGD(2) (IC(50) = 0.08 muM) >> PGI(2) (IC(50) = 2 muM) > PGE(1) (IC(50) = 6 muM) > PGF(2alpha) (IC(50) = 8 muM). Scatchard analysis of binding data from six normal subjects showed a single class of binding sites with a dissociation constant (K(d)) of 53 nM and 210 binding sites per platelet. This PGD(2) receptor assay was then used to study platelets from five patients with myeloproliferative disorders (polycythemia vera, essential thrombocythemia, and chronic myelogenous leukemia), as over 90% of these patients have platelets resistant to the effects of PGD(2) on aggregation and adenylate cyclase activity (1978. Blood.52: 618-626.). In the presence of 50 nM [(3)H]PGD(2), the patients' platelets bound 7.1+/-2.9 fmol ligand/10(8) platelets compared with 15.1+/-1 fmol/10(8) platelets in normals, a decrease of 53% (P < 0.01). Scatchard analysis showed that the K(d) of [(3)H]PGD(2) binding (33 nM) was comparable to normal platelets, which indicates that the decreased PGD(2) binding in these platelets represented fewer receptors rather than altered affinity of the ligand for the binding site. The 53% decrease in [(3)H]PGD(2) binding correlated with a 48% decrease in PGD(2)-activated platelet adenylate cyclase. The characterization of the platelet PGD(2) binding site provides further direct evidence that there are at least two PG receptors on platelets, one for PGE(1) and PGI(2), and a separate receptor for PGD(2). Direct binding analysis will be a useful tool for studying the role of PG in regulating platelet function, as demonstrated by the selective loss of PGD(2) binding sites in patients with myeloproliferative disorders.", "contents": "Characterization of the platelet prostaglandin D2 receptor. Loss of prostaglandin D2 receptors in platelets of patients with myeloproliferative disorders. Prostaglandin (PG) D(2) is synthesized in platelets at concentrations which could inhibit aggregation via activation of adenylate cyclase. To more directly define platelet-PG interactions, a binding assay has been developed for platelet PG receptors with [(3)H]PGD(2) as ligand. [(3)H]PGD(2) binding to intact platelets was saturable and rapid with the ligand bound by 3 min at 20 degrees C. PG competed with the [(3)H]PGD(2) binding site with a potency series: PGD(2) (IC(50) = 0.08 muM) >> PGI(2) (IC(50) = 2 muM) > PGE(1) (IC(50) = 6 muM) > PGF(2alpha) (IC(50) = 8 muM). Scatchard analysis of binding data from six normal subjects showed a single class of binding sites with a dissociation constant (K(d)) of 53 nM and 210 binding sites per platelet. This PGD(2) receptor assay was then used to study platelets from five patients with myeloproliferative disorders (polycythemia vera, essential thrombocythemia, and chronic myelogenous leukemia), as over 90% of these patients have platelets resistant to the effects of PGD(2) on aggregation and adenylate cyclase activity (1978. Blood.52: 618-626.). In the presence of 50 nM [(3)H]PGD(2), the patients' platelets bound 7.1+/-2.9 fmol ligand/10(8) platelets compared with 15.1+/-1 fmol/10(8) platelets in normals, a decrease of 53% (P < 0.01). Scatchard analysis showed that the K(d) of [(3)H]PGD(2) binding (33 nM) was comparable to normal platelets, which indicates that the decreased PGD(2) binding in these platelets represented fewer receptors rather than altered affinity of the ligand for the binding site. The 53% decrease in [(3)H]PGD(2) binding correlated with a 48% decrease in PGD(2)-activated platelet adenylate cyclase. The characterization of the platelet PGD(2) binding site provides further direct evidence that there are at least two PG receptors on platelets, one for PGE(1) and PGI(2), and a separate receptor for PGD(2). Direct binding analysis will be a useful tool for studying the role of PG in regulating platelet function, as demonstrated by the selective loss of PGD(2) binding sites in patients with myeloproliferative disorders."}
{"id": "PMID:222814", "title": "Secretion of cholesterol-rich lipoproteins by perfused livers of hypercholesterolemic rats.", "content": "Rats maintained on a high-fat diet supplemented with propylthiouracil develop a hypercholesterolemia, an increased serum level of apolipoprotein (apo) E, abnormal very low density lipoproteins (VLDL) and low density lipoproteins (LDL), and a fatty liver which contains cholesterol ester as its major lipid. The fatty liver secretes apoE into a recirculating perfusate at a significantly higher rate and produces cholesterol ester-rich, apoC-deficient VLDL with slower electrophoretic mobility than the triacylglycerol-rich VLDL produced by perfused normal livers. LDL, secreted in significant quantities by the perfused fatty liver, but not by the normal liver, is also cholesterol rich and contains apoE as well as apoB. The incorporation of [(3)H]leucine into apoVLDL and apoLDL secreted by the livers of the hypercholesterolemic animals and the apoVLDL secreted by the normal liver corresponds to the pattern visualized when the apoproteins are separated by polyacrylamide gel electrophoresis. Similar patterns are noted when non-recirculating perfusates are studied. These results indicate that the cholesterol ester-rich, apoC-deficient VLDL and the apoE-containing LDL found in the serum of hypercholesterolemic rats are not solely catabolic remnants of VLDL and chylomicrons but are secreted by the liver. Separation of the perfusate lipoproteins by agarose gel filtration revealed that most of the apoE secreted by the livers of hypercholesterolemic rats is found in the VLDL and LDL, whereas apoE secreted by the normal livers is distributed equally between VLDL, high density lipoproteins, and a low molecular weight fraction which corresponds to the virtually delipidated apoprotein. Thus the distribution of apoE among the lipoprotein fractions may be related to the total amount of cholesterol being transported in the circulation.", "contents": "Secretion of cholesterol-rich lipoproteins by perfused livers of hypercholesterolemic rats. Rats maintained on a high-fat diet supplemented with propylthiouracil develop a hypercholesterolemia, an increased serum level of apolipoprotein (apo) E, abnormal very low density lipoproteins (VLDL) and low density lipoproteins (LDL), and a fatty liver which contains cholesterol ester as its major lipid. The fatty liver secretes apoE into a recirculating perfusate at a significantly higher rate and produces cholesterol ester-rich, apoC-deficient VLDL with slower electrophoretic mobility than the triacylglycerol-rich VLDL produced by perfused normal livers. LDL, secreted in significant quantities by the perfused fatty liver, but not by the normal liver, is also cholesterol rich and contains apoE as well as apoB. The incorporation of [(3)H]leucine into apoVLDL and apoLDL secreted by the livers of the hypercholesterolemic animals and the apoVLDL secreted by the normal liver corresponds to the pattern visualized when the apoproteins are separated by polyacrylamide gel electrophoresis. Similar patterns are noted when non-recirculating perfusates are studied. These results indicate that the cholesterol ester-rich, apoC-deficient VLDL and the apoE-containing LDL found in the serum of hypercholesterolemic rats are not solely catabolic remnants of VLDL and chylomicrons but are secreted by the liver. Separation of the perfusate lipoproteins by agarose gel filtration revealed that most of the apoE secreted by the livers of hypercholesterolemic rats is found in the VLDL and LDL, whereas apoE secreted by the normal livers is distributed equally between VLDL, high density lipoproteins, and a low molecular weight fraction which corresponds to the virtually delipidated apoprotein. Thus the distribution of apoE among the lipoprotein fractions may be related to the total amount of cholesterol being transported in the circulation."}
{"id": "PMID:222819", "title": "Isolation of functionally active acini from bovine mammary gland.", "content": "Conditions to obtain high yields of intact acini from lactating bovine mammary glands and certain structural and functional characteristics of isolated acini were investigated. A two-factor experiment with three collagenase concentrations (100, 150, and 200 mg/100 ml) and incubation periods (40, 60, and 90 min) demonstrated that increases in both factors significantly increased net acini yield. Largest amounts of acini obtained, based on content of deoxyribonucleic acid, were 10.3% of the original tissue. Morphologically, fractions consisted primarily of acini or large cell clumps, and nearly all cells excluded trypan blue. Acini cultured in complete nutrient medium incorporated radioactive leucine into proteins. When acini were incubated in medium without supplemental amino acids, specific activity of synthesized proteins was correlated negatively with incubation time. During pulse labeling with radioactive L-leucine over 16 min, true labeling of acinar proteins occurred after 4 min. Sequential kinetics of pulse-chase labeling demonstrated a response pattern unique to the in vitro acinar system. Acinar protein synthesis was inhibited by cycloheximide and strongly stimulated by by 3',5'-cyclic adenosine monophosphate.", "contents": "Isolation of functionally active acini from bovine mammary gland. Conditions to obtain high yields of intact acini from lactating bovine mammary glands and certain structural and functional characteristics of isolated acini were investigated. A two-factor experiment with three collagenase concentrations (100, 150, and 200 mg/100 ml) and incubation periods (40, 60, and 90 min) demonstrated that increases in both factors significantly increased net acini yield. Largest amounts of acini obtained, based on content of deoxyribonucleic acid, were 10.3% of the original tissue. Morphologically, fractions consisted primarily of acini or large cell clumps, and nearly all cells excluded trypan blue. Acini cultured in complete nutrient medium incorporated radioactive leucine into proteins. When acini were incubated in medium without supplemental amino acids, specific activity of synthesized proteins was correlated negatively with incubation time. During pulse labeling with radioactive L-leucine over 16 min, true labeling of acinar proteins occurred after 4 min. Sequential kinetics of pulse-chase labeling demonstrated a response pattern unique to the in vitro acinar system. Acinar protein synthesis was inhibited by cycloheximide and strongly stimulated by by 3',5'-cyclic adenosine monophosphate."}
{"id": "PMID:222820", "title": "Pharmacokinetics and amounts of 25-hydroxycholecalciferol in sheep affected by osteodystrophy.", "content": "Amounts of 25-hydroxycholecalciferol in plasma were measured in two groups (A and B) of lambs (Experiment 1) and in two groups (C and D) of wethers (Experiment 2). Groups A (eight lambs) and C (nine wethers) consisted of animals born and raised in total confinement; these animals exhibited an osteodystrophic condition. Groups B (four lambs) and D (10 wethers) consisted of healthy animals born and raised in a conventional barn with free access to an open barn yard (i.e. exposure to sunshine). The 25-hydroxycholecalciferol in plasma of both groups of sick animals, Group A (12.9 ng/ml) and Group C (18.0 ng/ml), were lower than the amounts of the two corresponding groups of healthy animals. Group B (29.2 ng/ml and Group D (32.5 ng/ml). Pharmacokinetic analysis of 25-hydroxycholecalciferol in affected lambs following intramuscular injection of 1,000,000 IU vitamin D3 indicated that transport of vitamin D3 from the site of injection to the liver and its metabolism to 25-hydroxycholecalciferol were rapid. Peak 25-hydroxycholecalciferol occurred at .6 wk, and half-life was 3.1 wk.", "contents": "Pharmacokinetics and amounts of 25-hydroxycholecalciferol in sheep affected by osteodystrophy. Amounts of 25-hydroxycholecalciferol in plasma were measured in two groups (A and B) of lambs (Experiment 1) and in two groups (C and D) of wethers (Experiment 2). Groups A (eight lambs) and C (nine wethers) consisted of animals born and raised in total confinement; these animals exhibited an osteodystrophic condition. Groups B (four lambs) and D (10 wethers) consisted of healthy animals born and raised in a conventional barn with free access to an open barn yard (i.e. exposure to sunshine). The 25-hydroxycholecalciferol in plasma of both groups of sick animals, Group A (12.9 ng/ml) and Group C (18.0 ng/ml), were lower than the amounts of the two corresponding groups of healthy animals. Group B (29.2 ng/ml and Group D (32.5 ng/ml). Pharmacokinetic analysis of 25-hydroxycholecalciferol in affected lambs following intramuscular injection of 1,000,000 IU vitamin D3 indicated that transport of vitamin D3 from the site of injection to the liver and its metabolism to 25-hydroxycholecalciferol were rapid. Peak 25-hydroxycholecalciferol occurred at .6 wk, and half-life was 3.1 wk."}
{"id": "PMID:222822", "title": "Endocrine factors in genetic improvement of milk production.", "content": "The endocrine role in lactation is undisputed, but attempts to correlate milk production with various endocrine products have had limited success. Recent work has suggested that placental hormones, in particular placental lactogen, may be an important regulator of lactation capacity. In addition to concentrations of hormones in blood, it is important to consider receptors in target tissue for the hormones. The concentration of receptors in a tissue may vary with genotype of the individual or under the influence of hormonal state. Other aspects of the target tissue's system for response also must be considered.", "contents": "Endocrine factors in genetic improvement of milk production. The endocrine role in lactation is undisputed, but attempts to correlate milk production with various endocrine products have had limited success. Recent work has suggested that placental hormones, in particular placental lactogen, may be an important regulator of lactation capacity. In addition to concentrations of hormones in blood, it is important to consider receptors in target tissue for the hormones. The concentration of receptors in a tissue may vary with genotype of the individual or under the influence of hormonal state. Other aspects of the target tissue's system for response also must be considered."}
{"id": "PMID:222824", "title": "Urinary excretion of cyclic AMP in bacterial infections.", "content": "Urinary cyclic AMP excretion was found to be increased in patients with severe bacterial infections and normal renal function. The observed changes appeared due to a combination of an increased filtered load plus augmented \"nephrogenous\" production in some patients; while in others, only an increase in the apparent \"nephrogenous\" production of cAMP could be found to account for the elevation in the total urinary excretion. Since total serum calcium was found to be low in most of these patients, increased PTH secretion to reduce urinary excretion of calcium may have been responsible for an increase in renal parenchymal production, and subsequent excretion of cyclic AMP. Although speculative, this theory is tenable in that ionized hypocalcemia exists in septic patients.", "contents": "Urinary excretion of cyclic AMP in bacterial infections. Urinary cyclic AMP excretion was found to be increased in patients with severe bacterial infections and normal renal function. The observed changes appeared due to a combination of an increased filtered load plus augmented \"nephrogenous\" production in some patients; while in others, only an increase in the apparent \"nephrogenous\" production of cAMP could be found to account for the elevation in the total urinary excretion. Since total serum calcium was found to be low in most of these patients, increased PTH secretion to reduce urinary excretion of calcium may have been responsible for an increase in renal parenchymal production, and subsequent excretion of cyclic AMP. Although speculative, this theory is tenable in that ionized hypocalcemia exists in septic patients."}
{"id": "PMID:222825", "title": "The evolution of a token economy programme for female chronic schizophrenic patients.", "content": "Token economy programmes are becoming an increasingly familiar sight in British psychiatric hospitals, yet many remain inflexible and prone to breakdown after a period in operation. This paper describes the evolution of a token economy for female chronic schizophrenic patients, where the nursing staff with minimal 'psychological' support and in dealing with a programme free of research constraints, aimed to increase the therapeutic potential of the system. The major developments arose from the need: (i) to extinguish the emergence of undesirable behaviour; (2) to develop a more individualized approach to treating patients' problems; (3) to keep consistent adequate records; (4) to re-establish contact with the community and (5) to cater for patients' varied responses to treatment.", "contents": "The evolution of a token economy programme for female chronic schizophrenic patients. Token economy programmes are becoming an increasingly familiar sight in British psychiatric hospitals, yet many remain inflexible and prone to breakdown after a period in operation. This paper describes the evolution of a token economy for female chronic schizophrenic patients, where the nursing staff with minimal 'psychological' support and in dealing with a programme free of research constraints, aimed to increase the therapeutic potential of the system. The major developments arose from the need: (i) to extinguish the emergence of undesirable behaviour; (2) to develop a more individualized approach to treating patients' problems; (3) to keep consistent adequate records; (4) to re-establish contact with the community and (5) to cater for patients' varied responses to treatment."}
{"id": "PMID:222826", "title": "Intraoral adenoid cystic carcinoma.", "content": "A case report of adenoid cytic carcinoma of the palate is presented. The clinical manifestations, diagnostic criteria, surgical resection, and prosthetic reconstruction of the patient are discussed.", "contents": "Intraoral adenoid cystic carcinoma. A case report of adenoid cytic carcinoma of the palate is presented. The clinical manifestations, diagnostic criteria, surgical resection, and prosthetic reconstruction of the patient are discussed."}
{"id": "PMID:222827", "title": "Inhalation challenge and pharmacologic studies of toluene diisocyanate (TDI)-sensitive workers.", "content": "Workers with \"sensitivity\" to toluene diisocyanate (TDI) studied in depth in an attempt to determine mechanisms of bronchial hyperreactivity. Tests included provocative inhalation challenge (PIC) with TDI and methacholine challenge. Blood samples obtained prior to and at various times after PIC were used to measure complement and split products of complement and plasma histamine levels and to determine dose-response slopes of lymphocyte cyclic adenosine monophosphate (cAMP) following stimulation with agonists. TDI-reactive individuals were all reactive to methacholine and responded to PIC with TDI by immediate, delayed, or dual bronchospastic reactions. No change in plasma histamine, total complement levels, or split products of complement were measurable. TDI reactors gave decreased lymphocyte cAMP dose response slopes to stimulation with isoproterenol, prostaglandin E1, and TDI, which suggests that impairment of adrenergic receptors may play an important role in TDI reactivity.", "contents": "Inhalation challenge and pharmacologic studies of toluene diisocyanate (TDI)-sensitive workers. Workers with \"sensitivity\" to toluene diisocyanate (TDI) studied in depth in an attempt to determine mechanisms of bronchial hyperreactivity. Tests included provocative inhalation challenge (PIC) with TDI and methacholine challenge. Blood samples obtained prior to and at various times after PIC were used to measure complement and split products of complement and plasma histamine levels and to determine dose-response slopes of lymphocyte cyclic adenosine monophosphate (cAMP) following stimulation with agonists. TDI-reactive individuals were all reactive to methacholine and responded to PIC with TDI by immediate, delayed, or dual bronchospastic reactions. No change in plasma histamine, total complement levels, or split products of complement were measurable. TDI reactors gave decreased lymphocyte cAMP dose response slopes to stimulation with isoproterenol, prostaglandin E1, and TDI, which suggests that impairment of adrenergic receptors may play an important role in TDI reactivity."}
{"id": "PMID:222830", "title": "Histochemical studies on Raillietina (Raillietina) johri (Cestoda: Davaineidae). I. Nonspecific and specific phosphatases.", "content": "Certain phosphatases have been localized by histochemical techniques in various tissues of a pigeon cestode, Raillietina (Raillietina) johri. Acid phosphatase (AcPase), alkaline phosphatase (AlPase) and adenosine triphosphatase (ATPase) were present in almost all structures: tegument; subtegumental muscles; subtegumental cells; excretory canal; testes; sperm ductules; vas deferens; cirrus sac; cirrus; ovary; receptaculum seminis; vagina; vitelline gland cells; oocytes; uterus; embryonated eggs. AlPase was absent in parenchyma, spermatocytes, spermatids and spermatozoa. AlPase activity was more intense in the tegument of mature gravid proglottides. AcPase and ATPase were visualized in various stages of spermatogenesis of the parasite. ATPase activity was also observed in chromosomes. 5'-nucleotidase (AMPase) activity was restricted to embryonated eggs only. Functional significance of these phosphatases is discussed.", "contents": "Histochemical studies on Raillietina (Raillietina) johri (Cestoda: Davaineidae). I. Nonspecific and specific phosphatases. Certain phosphatases have been localized by histochemical techniques in various tissues of a pigeon cestode, Raillietina (Raillietina) johri. Acid phosphatase (AcPase), alkaline phosphatase (AlPase) and adenosine triphosphatase (ATPase) were present in almost all structures: tegument; subtegumental muscles; subtegumental cells; excretory canal; testes; sperm ductules; vas deferens; cirrus sac; cirrus; ovary; receptaculum seminis; vagina; vitelline gland cells; oocytes; uterus; embryonated eggs. AlPase was absent in parenchyma, spermatocytes, spermatids and spermatozoa. AlPase activity was more intense in the tegument of mature gravid proglottides. AcPase and ATPase were visualized in various stages of spermatogenesis of the parasite. ATPase activity was also observed in chromosomes. 5'-nucleotidase (AMPase) activity was restricted to embryonated eggs only. Functional significance of these phosphatases is discussed."}
{"id": "PMID:222836", "title": "Ultrastructural immunohistochemical localization of adrenocorticotropin and beta-lipotropin in the rat brain.", "content": "In an attempt to identify the cells and organellel containing ACTH and beta-lipotropin in the rat brain, an immunocytochemical localization of these two peptides was performed at the electron microscopic level. Both ACTH and beta-lipotropin were localized in dense core vesicles of about 60-80 nm in diameter. Using serial sections, it has been possible to demonstrate that these peptides are contained not only in the same neuronal cell bodies, but also in the same dense core vesicles.", "contents": "Ultrastructural immunohistochemical localization of adrenocorticotropin and beta-lipotropin in the rat brain. In an attempt to identify the cells and organellel containing ACTH and beta-lipotropin in the rat brain, an immunocytochemical localization of these two peptides was performed at the electron microscopic level. Both ACTH and beta-lipotropin were localized in dense core vesicles of about 60-80 nm in diameter. Using serial sections, it has been possible to demonstrate that these peptides are contained not only in the same neuronal cell bodies, but also in the same dense core vesicles."}
{"id": "PMID:222837", "title": "The specific detection of foot-and-mouth disease virus whole particle antigen (140S) by enzyme labelled immunosorbent assay.", "content": "A solid-phase micro-enzyme-labelled immunosorbent assay (ELISA) using guinea pig antiserum against purified (140S) inactivated foot-and-mouth disease (FMD) virus has been used in a sandwich technique to specifically measure 140S virus in the presence of 12S material.", "contents": "The specific detection of foot-and-mouth disease virus whole particle antigen (140S) by enzyme labelled immunosorbent assay. A solid-phase micro-enzyme-labelled immunosorbent assay (ELISA) using guinea pig antiserum against purified (140S) inactivated foot-and-mouth disease (FMD) virus has been used in a sandwich technique to specifically measure 140S virus in the presence of 12S material."}
{"id": "PMID:222838", "title": "The serological diagnosis of whooping cough.", "content": "Indirect haemagglutination (IHA), agglutination and complement fixation tests (CFT) for Bordetella pertussis antibodies were compared on paired sera from 52 suspected cases of whooping cough and single sera from 83 children with no recent history of whooping cough. All three tests detected serotype antibodies 1, 2 and 3, but the IHA test was the most sensitive; in seven cases it was the only test to show a rise in titre. It is recommended, particularly with vaccinated children, that the serological diagnosis of whooping cough should be based upon a rise in titre. There should be a gap of at least 2-4 weeks between serum samples, depending on the age and vaccination state of the child. The CFT appears to detect a different antibody from that detected by the other two tests, and in three cases it was the only test to show a rise in titre.", "contents": "The serological diagnosis of whooping cough. Indirect haemagglutination (IHA), agglutination and complement fixation tests (CFT) for Bordetella pertussis antibodies were compared on paired sera from 52 suspected cases of whooping cough and single sera from 83 children with no recent history of whooping cough. All three tests detected serotype antibodies 1, 2 and 3, but the IHA test was the most sensitive; in seven cases it was the only test to show a rise in titre. It is recommended, particularly with vaccinated children, that the serological diagnosis of whooping cough should be based upon a rise in titre. There should be a gap of at least 2-4 weeks between serum samples, depending on the age and vaccination state of the child. The CFT appears to detect a different antibody from that detected by the other two tests, and in three cases it was the only test to show a rise in titre."}
{"id": "PMID:222839", "title": "Suppression of the in vitro secondary response to syngeneic tumor and of in vivo tumor therapy with immune cells by culture-induced suppressor cells.", "content": "Mice with advanced disseminated syngeneic tumor can be successfully treated with a combination of chemotherapy and adoptively transferred syngeneic immune cells. We have previously demonstrated that in vivo primed cells secondarily sensitized in vitro became more effective in tumor therapy, whereas primed cells cultured for 5 days without tumor stimulation became less effective than an equal number of uncultured fresh primed cells. Therefore, we examined stimulated and unstimulated cultures of tumor-primed cells for the presence of culture-induced suppressor cells, and determined whether in vivo tumor therapy with immune cells could be inhibited by concurrent inoculation of immune effector cells and cultured normal spleen cells, which contain culture-induced suppressor cells but are devoid of additional effector cells. The in vitro primary allogeneic response was suppressed by cultured normal spleen cells, or tumor-primed spleen cells previously cultured for 5 days with or without tumor stimulation. In vitro secondary sensitization to syngeneic tumor was suppressed by normal or tumor-primed cells that had previously been cultured for 5 days without stimulation. The majority of this suppression was mediated by T cells in the cultured populations. The efficacy of fresh tumor-primed cells, as well as primed cells secondarily sensitized in vitro, in adoptive chemoimmunotherapy of advanced tumor was diminished by concurrent inoculation of cultured normal cells. The cells mediating suppression of in vivo therapy required previous in vitro culture for induction, and were radiation sensitive.", "contents": "Suppression of the in vitro secondary response to syngeneic tumor and of in vivo tumor therapy with immune cells by culture-induced suppressor cells. Mice with advanced disseminated syngeneic tumor can be successfully treated with a combination of chemotherapy and adoptively transferred syngeneic immune cells. We have previously demonstrated that in vivo primed cells secondarily sensitized in vitro became more effective in tumor therapy, whereas primed cells cultured for 5 days without tumor stimulation became less effective than an equal number of uncultured fresh primed cells. Therefore, we examined stimulated and unstimulated cultures of tumor-primed cells for the presence of culture-induced suppressor cells, and determined whether in vivo tumor therapy with immune cells could be inhibited by concurrent inoculation of immune effector cells and cultured normal spleen cells, which contain culture-induced suppressor cells but are devoid of additional effector cells. The in vitro primary allogeneic response was suppressed by cultured normal spleen cells, or tumor-primed spleen cells previously cultured for 5 days with or without tumor stimulation. In vitro secondary sensitization to syngeneic tumor was suppressed by normal or tumor-primed cells that had previously been cultured for 5 days without stimulation. The majority of this suppression was mediated by T cells in the cultured populations. The efficacy of fresh tumor-primed cells, as well as primed cells secondarily sensitized in vitro, in adoptive chemoimmunotherapy of advanced tumor was diminished by concurrent inoculation of cultured normal cells. The cells mediating suppression of in vivo therapy required previous in vitro culture for induction, and were radiation sensitive."}
{"id": "PMID:222840", "title": "Limited trypsin cleavage distinguishes MHC and thymus-leukemia antigens.", "content": "A simple technique is presented for the identification of particular cell membrane antigens. The method employs labeled membrane antigens that are isolated immunospecifically and subjected to limited trypsin digestion followed by polyacrylamide gel electrophoresis in detergent. A large \"core\" peptide is produced by proteolysis of murine thymus-leukemia antigens (TLA) and from antigens of the major histocompatibility complex (MHC). The tryptic cores from H-2K and H-2D are regularly distinguishable from the thymus-leukemia antigens (TLA) by gel electrophoresis in one dimension. This chemical distinction is particularly important in the analysis of antigen mixtures isolated with antisera specific for beta 2 microglobulin. These techniques have been used to identify thymus-restricted beta 2 microglobulin-associated antigens on cell membranes from mouse, man, guinea pig, and monkey. In appropriate inbred mouse strains, these are the TLA and it is proposed that in the three other species examined they may be analogues, although not necessarily homologues, of TLA. The broad species distribution of these thymus-restricted cell membrane antigens suggests that they are involved in the differentiation of thymus-dependent lymphocytes (T cells).", "contents": "Limited trypsin cleavage distinguishes MHC and thymus-leukemia antigens. A simple technique is presented for the identification of particular cell membrane antigens. The method employs labeled membrane antigens that are isolated immunospecifically and subjected to limited trypsin digestion followed by polyacrylamide gel electrophoresis in detergent. A large \"core\" peptide is produced by proteolysis of murine thymus-leukemia antigens (TLA) and from antigens of the major histocompatibility complex (MHC). The tryptic cores from H-2K and H-2D are regularly distinguishable from the thymus-leukemia antigens (TLA) by gel electrophoresis in one dimension. This chemical distinction is particularly important in the analysis of antigen mixtures isolated with antisera specific for beta 2 microglobulin. These techniques have been used to identify thymus-restricted beta 2 microglobulin-associated antigens on cell membranes from mouse, man, guinea pig, and monkey. In appropriate inbred mouse strains, these are the TLA and it is proposed that in the three other species examined they may be analogues, although not necessarily homologues, of TLA. The broad species distribution of these thymus-restricted cell membrane antigens suggests that they are involved in the differentiation of thymus-dependent lymphocytes (T cells)."}
{"id": "PMID:222841", "title": "Lysosomal enzymes in inflammatory synovial effusions.", "content": "The concentrations of several polymorphonuclear neutrophilic lysosomal constituents were quantitated by immunochemical and enzymatic assays in 28 inflammatory and 9 noninflammatory synovial fluids. The quantities of lactoferrin, myeloperoxidase, and enzymatically determined lysozyme were covariate with the neutrophil count. Enzymatic activities measured with synthetic substrates developed for the assay of chymotryptic-like cationic protein (cathepsin G) and elastase, along with immunochemically determined lysozyme, were independent of the neutrophil count. Although the latter assays were developed and standardized with human neutrophilic lysosomal constituents, they measure different activities in inflammatory synovial effusions. No elastase was detected if elastin was used as the substrate. Regardless of the source of the enzymes, there was a negative correlation between their concentration and the degree of radiographic destruction of the joint from which the fluid was obtained. Lysosomal enzymes in solution in synovial fluid are not likely to be primarily involved in cartilage destruction.", "contents": "Lysosomal enzymes in inflammatory synovial effusions. The concentrations of several polymorphonuclear neutrophilic lysosomal constituents were quantitated by immunochemical and enzymatic assays in 28 inflammatory and 9 noninflammatory synovial fluids. The quantities of lactoferrin, myeloperoxidase, and enzymatically determined lysozyme were covariate with the neutrophil count. Enzymatic activities measured with synthetic substrates developed for the assay of chymotryptic-like cationic protein (cathepsin G) and elastase, along with immunochemically determined lysozyme, were independent of the neutrophil count. Although the latter assays were developed and standardized with human neutrophilic lysosomal constituents, they measure different activities in inflammatory synovial effusions. No elastase was detected if elastin was used as the substrate. Regardless of the source of the enzymes, there was a negative correlation between their concentration and the degree of radiographic destruction of the joint from which the fluid was obtained. Lysosomal enzymes in solution in synovial fluid are not likely to be primarily involved in cartilage destruction."}
{"id": "PMID:222843", "title": "Cyclic nucleotide phosphodiesterase activity in human peripheral blood lymphocytes and monocytes.", "content": "cAMP and cGMP phosphodiesterase (PDE) activity was assayed in human peripheral blood lymphocytes purified by isopycnic centrifugation as well as in lymphocyte preparations further purified to remove contaminating platelets and monocytes. The 16,000 X G supernatant from sonicates of each of these cell preparations contained two hydrolytic activities for cAMP with apparent Km of 1.1 to 2.5 microM and 33 to 66 microM, and a single hydrolytic activity for cGMP with an apparent Km of 6 to 25 microM. When lymphocytes were disrupted by Dounce homogenization, there was only a single, low Km cAMP PDE activity in the homogenate; however, the 16,000 X G supernatant demonstrated 2 Km similar to that seen in sonicated lymphocytes. Treatment of the Dounce preparations with 0.5% Triton X-100 or 1.0% NP-40 converted these preparations to activities similar to those seen in sonicated preparations. cGMP hydrolytic activity was low or absent in the Dounce preparations and was not altered by centrifugation; however, it was markedly enhanced by detergent extraction. These data indicate that human peripheral blood lymphocytes and monocytes have PDE activities similar to those seen in other tissues.", "contents": "Cyclic nucleotide phosphodiesterase activity in human peripheral blood lymphocytes and monocytes. cAMP and cGMP phosphodiesterase (PDE) activity was assayed in human peripheral blood lymphocytes purified by isopycnic centrifugation as well as in lymphocyte preparations further purified to remove contaminating platelets and monocytes. The 16,000 X G supernatant from sonicates of each of these cell preparations contained two hydrolytic activities for cAMP with apparent Km of 1.1 to 2.5 microM and 33 to 66 microM, and a single hydrolytic activity for cGMP with an apparent Km of 6 to 25 microM. When lymphocytes were disrupted by Dounce homogenization, there was only a single, low Km cAMP PDE activity in the homogenate; however, the 16,000 X G supernatant demonstrated 2 Km similar to that seen in sonicated lymphocytes. Treatment of the Dounce preparations with 0.5% Triton X-100 or 1.0% NP-40 converted these preparations to activities similar to those seen in sonicated preparations. cGMP hydrolytic activity was low or absent in the Dounce preparations and was not altered by centrifugation; however, it was markedly enhanced by detergent extraction. These data indicate that human peripheral blood lymphocytes and monocytes have PDE activities similar to those seen in other tissues."}
{"id": "PMID:222846", "title": "Simultaneous radioimmunoassay for specific antibodies to members of the human herpesvirus group.", "content": "A method of described for the simultaneous radioimmunoassay (RIA) for antibody to members of the human herpesvirus group. The RIA is compared with some of the conventional serologic techniques used to quantitate antibody to these viruses (Epstein-Barr virus, cytomegalovirus, herpesvirus type 1 and varicella-zoster virus). Color-coded beads, each coated with the antigens of a different herpesvirus, were similtaneously placed in a well which contained a human serum to be assayed for antibody to each of these 4 viruses. The results of this test were compared with the results obtained when the serum was assayed for antibody to the 4 viruses in 4 separate tests. We conclude that the antigen-antibody reactions do not significantly interfere with each other when a serum is assayed for antibody to the 4 viruses simultaneously. A comparison of the RIA with conventional serologic techniques shows excellent correlation in the antibody titers obtained. Features of the solid-phase RIA allow significant savings of time, reagents and space, and thus make it feasible for the small laboratory to screen large numbers of sera for antibody to a variety of antigens.", "contents": "Simultaneous radioimmunoassay for specific antibodies to members of the human herpesvirus group. A method of described for the simultaneous radioimmunoassay (RIA) for antibody to members of the human herpesvirus group. The RIA is compared with some of the conventional serologic techniques used to quantitate antibody to these viruses (Epstein-Barr virus, cytomegalovirus, herpesvirus type 1 and varicella-zoster virus). Color-coded beads, each coated with the antigens of a different herpesvirus, were similtaneously placed in a well which contained a human serum to be assayed for antibody to each of these 4 viruses. The results of this test were compared with the results obtained when the serum was assayed for antibody to the 4 viruses in 4 separate tests. We conclude that the antigen-antibody reactions do not significantly interfere with each other when a serum is assayed for antibody to the 4 viruses simultaneously. A comparison of the RIA with conventional serologic techniques shows excellent correlation in the antibody titers obtained. Features of the solid-phase RIA allow significant savings of time, reagents and space, and thus make it feasible for the small laboratory to screen large numbers of sera for antibody to a variety of antigens."}
{"id": "PMID:222847", "title": "The use of polymyxin B and C3H/HeJ mouse spleen cells as criteria for endotoxin contamination.", "content": "We have performed experiments designed to evaluate the potential contribution of endotoxin contamination to lymphocyte reponses. Saline and EDTA extracts of 4 different strains of gram negative bacteria were examined for their capacity to initiate mitogenic responses in murine spleen cells. As compared to phenol extracts of these bacteria which contain primarily lipopolysaccharide-LPS, these saline and EDTA extracts were significantly less active in this assay. The mitogenic activity which was present was also manifest in spleen cells from the C3H/HeJ mouse, whereas phenol-extracted LPS preparations were inactive. In addition, mitogenic activity of saline and EDTA extracts was not blocked by polymyxin B, an agent known to abrogate LPS mediated responses. We conclude that LPS contamination may not normally be as significant a problem as had earlier been assumed. However, when endotoxin contamination is present, neither the use of C3H/HeJ spleen cells nor polymyxin B is an appropriate test to evaluate this possibility.", "contents": "The use of polymyxin B and C3H/HeJ mouse spleen cells as criteria for endotoxin contamination. We have performed experiments designed to evaluate the potential contribution of endotoxin contamination to lymphocyte reponses. Saline and EDTA extracts of 4 different strains of gram negative bacteria were examined for their capacity to initiate mitogenic responses in murine spleen cells. As compared to phenol extracts of these bacteria which contain primarily lipopolysaccharide-LPS, these saline and EDTA extracts were significantly less active in this assay. The mitogenic activity which was present was also manifest in spleen cells from the C3H/HeJ mouse, whereas phenol-extracted LPS preparations were inactive. In addition, mitogenic activity of saline and EDTA extracts was not blocked by polymyxin B, an agent known to abrogate LPS mediated responses. We conclude that LPS contamination may not normally be as significant a problem as had earlier been assumed. However, when endotoxin contamination is present, neither the use of C3H/HeJ spleen cells nor polymyxin B is an appropriate test to evaluate this possibility."}
{"id": "PMID:222850", "title": "Impaired H2 histamine granulocyte response in active atopic eczema.", "content": "Many clinical abnormalities in atopic eczema have been attributed to an imbalance in autonomic nervous system control, specifically a partial blockade of beta-adrenergic responsiveness. The lysosomal enzyme beta-glucuronidase is released from granulocytes during in vitro incubation with complement-activated zymosan particles. Isoproterenol will inhibit the release of this lysosomal enzyme from the granulocyte and the isoproterenol effect is associated with increased granulocyte cyclic AMP formation. In atopic eczema and asthma, this granulocyte response to isoproterenol is impaired. Histamine also inhibits in vitro zymosan induced release of beta-glucuronidase and this is an H2 histamine effect. In asthma, this H2 histamine response is diminished. In the following study, we found a similar impairment in histamine inhibition of beta-glucuronidase release and formation of granulocyte cAMP in atopic eczema. This defect was found only in granulocytes from patients with active eczema. Thus in active atopic eczema, defects in the pharmacological response of the granulocyte are not limited to beta-adrenergic agonists but include H2 histamine activity.", "contents": "Impaired H2 histamine granulocyte response in active atopic eczema. Many clinical abnormalities in atopic eczema have been attributed to an imbalance in autonomic nervous system control, specifically a partial blockade of beta-adrenergic responsiveness. The lysosomal enzyme beta-glucuronidase is released from granulocytes during in vitro incubation with complement-activated zymosan particles. Isoproterenol will inhibit the release of this lysosomal enzyme from the granulocyte and the isoproterenol effect is associated with increased granulocyte cyclic AMP formation. In atopic eczema and asthma, this granulocyte response to isoproterenol is impaired. Histamine also inhibits in vitro zymosan induced release of beta-glucuronidase and this is an H2 histamine effect. In asthma, this H2 histamine response is diminished. In the following study, we found a similar impairment in histamine inhibition of beta-glucuronidase release and formation of granulocyte cAMP in atopic eczema. This defect was found only in granulocytes from patients with active eczema. Thus in active atopic eczema, defects in the pharmacological response of the granulocyte are not limited to beta-adrenergic agonists but include H2 histamine activity."}
{"id": "PMID:222852", "title": "Pharyngoconjunctival fever caused by adenovirus type 4: report of a swimming pool-related outbreak with recovery of virus from pool water.", "content": "During the summer of 1977, an outbreak of pharyngoconjunctival fever (PCF) occurred at a private recreational facility in Georgia. A total of 72 cases of PCF was identified. Adenovirus type 4 (AV-4) was recovered from conjunctival or pharyngeal swab specimens from 20 of 26 persons in the group of cases tested. AV-4 was also recovered, for the first time reported in the literature, from two concentrated samples of water obtained from the swimming pool at the facility on different dates. All persons affected had had direct or indirect contact with the pool. A linear relation between the amount of time spent in the water and the attack rate was demonstrated (r = 0.929, P less than 0.01). Investigation showed that inadequate amounts of chlorine had been added to the pool water. Frequently, levels of free chlorine were below the recommended level of 0.4 mg/liter. Breakpoint chlorination and closing of the pool for the summer stopped the spread of PCF.", "contents": "Pharyngoconjunctival fever caused by adenovirus type 4: report of a swimming pool-related outbreak with recovery of virus from pool water. During the summer of 1977, an outbreak of pharyngoconjunctival fever (PCF) occurred at a private recreational facility in Georgia. A total of 72 cases of PCF was identified. Adenovirus type 4 (AV-4) was recovered from conjunctival or pharyngeal swab specimens from 20 of 26 persons in the group of cases tested. AV-4 was also recovered, for the first time reported in the literature, from two concentrated samples of water obtained from the swimming pool at the facility on different dates. All persons affected had had direct or indirect contact with the pool. A linear relation between the amount of time spent in the water and the attack rate was demonstrated (r = 0.929, P less than 0.01). Investigation showed that inadequate amounts of chlorine had been added to the pool water. Frequently, levels of free chlorine were below the recommended level of 0.4 mg/liter. Breakpoint chlorination and closing of the pool for the summer stopped the spread of PCF."}
{"id": "PMID:222853", "title": "Interrelationship between coronary artery occlusion, high-density lipoprotein cholesterol, and alcohol intake.", "content": "The interrelationships between coronary artery occlusion, alcohol consumption, and plasma levels of HDL cholesterol were investigated in 718 male patients undergoing coronary arteriography. A statistically significant inverse relationship was seen between the extent of coronary occlusion and alcohol intake and between coronary occlusion and plasma HDL cholesterol levels. A positive association was observed between the amounts of alcohol consumed and plasma HDL cholesterol levels, as well as between alcohol consumption and history of smoking. The findings of the present study suggest that the \"retarding\" effect of alcohol on coronary artery disease may be at least partially explained by the alcohol-induced rise of plasma HDL cholesterol.", "contents": "Interrelationship between coronary artery occlusion, high-density lipoprotein cholesterol, and alcohol intake. The interrelationships between coronary artery occlusion, alcohol consumption, and plasma levels of HDL cholesterol were investigated in 718 male patients undergoing coronary arteriography. A statistically significant inverse relationship was seen between the extent of coronary occlusion and alcohol intake and between coronary occlusion and plasma HDL cholesterol levels. A positive association was observed between the amounts of alcohol consumed and plasma HDL cholesterol levels, as well as between alcohol consumption and history of smoking. The findings of the present study suggest that the \"retarding\" effect of alcohol on coronary artery disease may be at least partially explained by the alcohol-induced rise of plasma HDL cholesterol."}
{"id": "PMID:222854", "title": "Evidence for transfer of folate compounds by a specialized erythrocyte membrane system.", "content": "Transfer of folate compounds was studied in human erythrocytes. At steady state, the measured distribution ratio of 5-CH3-H4-folate in erythrocyte suspensions exceeded the ratio predicted from the chloride distribution ratio by a factor of 1.58, suggesting that human erythrocytes concentrate folate. Because folate compounds are anionic at physiologic pH, we investigated the possibility that transport occurs via the inorganic anion channel associated with the predominant integral membrane protein, band 3. Erythrocyte uptake of 5-CH3-H4-folate was decreased (60% to 80%) by several known inhibitors of anion transport--pyridoxal phosphate, dipyridamole, phlorizin, and SITS. However, unlike the inorganic anion transfer system, 5-CH3-H4-folate uptake was only slightly decreased by DIDS; was reduced 50% to 70% by the sulfhydryl reagents NEM, PMB, and pCMBS; and was not affected by the proteolytic enzymes trypsin, chymotrypsin, and pronase. These studies suggest that folate compounds are transported by a specialized carrier system, independent of the inorganic anion channel, which contains sulfhydryl and amino groups. In contrast to 5-CH3-H4-folate transfer, uptake of pteroylglutamic acid was either unaffected or somewhat increased by these membrane modifications. This result indicates that the human erythrocyte transports the reduced and oxidized forms of the vitamin by entirely separate mechanisms.", "contents": "Evidence for transfer of folate compounds by a specialized erythrocyte membrane system. Transfer of folate compounds was studied in human erythrocytes. At steady state, the measured distribution ratio of 5-CH3-H4-folate in erythrocyte suspensions exceeded the ratio predicted from the chloride distribution ratio by a factor of 1.58, suggesting that human erythrocytes concentrate folate. Because folate compounds are anionic at physiologic pH, we investigated the possibility that transport occurs via the inorganic anion channel associated with the predominant integral membrane protein, band 3. Erythrocyte uptake of 5-CH3-H4-folate was decreased (60% to 80%) by several known inhibitors of anion transport--pyridoxal phosphate, dipyridamole, phlorizin, and SITS. However, unlike the inorganic anion transfer system, 5-CH3-H4-folate uptake was only slightly decreased by DIDS; was reduced 50% to 70% by the sulfhydryl reagents NEM, PMB, and pCMBS; and was not affected by the proteolytic enzymes trypsin, chymotrypsin, and pronase. These studies suggest that folate compounds are transported by a specialized carrier system, independent of the inorganic anion channel, which contains sulfhydryl and amino groups. In contrast to 5-CH3-H4-folate transfer, uptake of pteroylglutamic acid was either unaffected or somewhat increased by these membrane modifications. This result indicates that the human erythrocyte transports the reduced and oxidized forms of the vitamin by entirely separate mechanisms."}
{"id": "PMID:222855", "title": "Lipid metabolism in cultured cells. XVIII. Comparative uptake of low density and high density lipoproteins by normal, hypercholesterolemic and tumor virus-transformed human fibroblasts.", "content": "Serum lipoproteins control cell cholesterol content by regulating its uptake, biosynthesis, and excretion. Monolayers of cultured fibroblasts were used to study interactions with human high density (HDL) and low density (LDL) lipoproteins doubly labeled with [(3)H]cholesterol and (125)I in the apoprotein moiety. In the binding assay for LDL, the absence of specific LDL receptors in type II hypercholesterolemic fibroblasts was confirmed, whereas monolayers of virus-transformed human lung fibroblasts (VA-4) exhibited LDL binding characteristics essentially the same as normal lung fibroblasts. In the studies of HDL binding, specific HDL binding sites were demonstrated in normal and virus-transformed fibroblasts. In addition, type II hypercholesterolemic cells, despite the loss of LDL receptors, retained normal HDL binding sites. No significant competition was displayed between the two lipoprotein classes for their respective binding sites over a 5-fold concentration range. In VA-4 cells, the amount of lipoprotein required to saturate half the receptor sites was 3.5 micro g/ml (9 x 10(-9) M) for LDL and 9.1 micro g/ml (9 x 10(-8) M) for HDL. Pronase treatment reduced LDL binding by more than half but had no effect on HDL binding. Chloroquine, a lysomal enzyme inhibitor, stimulated net LDL uptake 3.5-fold by increasing internalized LDL but had essentially no effect on HDL uptake. Further experiments were conducted using doubly labeled lipoproteins to characterize the interaction of LDL and HDL with cells. While the cholesterol and protein moieties of LDL were incorporated into cells at similar rates, the uptake of the cholesterol moiety of HDL was 5 to 10 times more rapid than that of the protein component. Furthermore, the apoprotein component of LDL is extensively degraded following exposure, whereas the apoprotein moiety of HDL retains its macromolecular chromatographic characteristics. These results indicate that HDL and LDL bind to cultured cells at separate sites and that further processing of the two lipoprotein classes appears to take place by fundamentally different mechanisms.-Wu, J-D., J. Butler, and J. M. Bailey. Lipid metabolism in cultured cells XVIII. Comparative uptake of low density and high density lipoproteins by normal, hypercholesterolemic, and tumor virus-transformed human fibroblasts.", "contents": "Lipid metabolism in cultured cells. XVIII. Comparative uptake of low density and high density lipoproteins by normal, hypercholesterolemic and tumor virus-transformed human fibroblasts. Serum lipoproteins control cell cholesterol content by regulating its uptake, biosynthesis, and excretion. Monolayers of cultured fibroblasts were used to study interactions with human high density (HDL) and low density (LDL) lipoproteins doubly labeled with [(3)H]cholesterol and (125)I in the apoprotein moiety. In the binding assay for LDL, the absence of specific LDL receptors in type II hypercholesterolemic fibroblasts was confirmed, whereas monolayers of virus-transformed human lung fibroblasts (VA-4) exhibited LDL binding characteristics essentially the same as normal lung fibroblasts. In the studies of HDL binding, specific HDL binding sites were demonstrated in normal and virus-transformed fibroblasts. In addition, type II hypercholesterolemic cells, despite the loss of LDL receptors, retained normal HDL binding sites. No significant competition was displayed between the two lipoprotein classes for their respective binding sites over a 5-fold concentration range. In VA-4 cells, the amount of lipoprotein required to saturate half the receptor sites was 3.5 micro g/ml (9 x 10(-9) M) for LDL and 9.1 micro g/ml (9 x 10(-8) M) for HDL. Pronase treatment reduced LDL binding by more than half but had no effect on HDL binding. Chloroquine, a lysomal enzyme inhibitor, stimulated net LDL uptake 3.5-fold by increasing internalized LDL but had essentially no effect on HDL uptake. Further experiments were conducted using doubly labeled lipoproteins to characterize the interaction of LDL and HDL with cells. While the cholesterol and protein moieties of LDL were incorporated into cells at similar rates, the uptake of the cholesterol moiety of HDL was 5 to 10 times more rapid than that of the protein component. Furthermore, the apoprotein component of LDL is extensively degraded following exposure, whereas the apoprotein moiety of HDL retains its macromolecular chromatographic characteristics. These results indicate that HDL and LDL bind to cultured cells at separate sites and that further processing of the two lipoprotein classes appears to take place by fundamentally different mechanisms.-Wu, J-D., J. Butler, and J. M. Bailey. Lipid metabolism in cultured cells XVIII. Comparative uptake of low density and high density lipoproteins by normal, hypercholesterolemic, and tumor virus-transformed human fibroblasts."}
{"id": "PMID:222856", "title": "Secondary structure in very low density and intermediate density lipoproteins of human serum.", "content": "We have studies the secondary structures of the protein moieties of very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL) of human serum by circular dichroism (CD). Two potential complications in the application of this technique to lipoproteins have been evaluated. First, using chronographic potentiometry in CD measurements of VLDL fractions of different mean particle diameters, we have analyzed statistically the CD signals in order to define the limits imposed by light scattering with respect to both particle diameter and wavelength. We found that CD measurements can be made to as low as 210 nm on particles of 520 A or smaller, and to 194 nm on particles of 450 A and below. Second, we have evaluated the CD contribution of lipid chromophores. Despite the high ratio of lipid to protein, the relative CD effect of the lipids is smaller than for low density lipoproteins (LDL). due to the extremely small ellipticity of natural VLDL triglycerides. Thus, CD measurements can be obtained with confidence on the preponderant bulk of normal VLDL. For the first time we report the CD spectra of human VLDL and IDL. In contrast with human LDL and the lipoproteins of the hypercholesterolemic rabbit, the entire CD SPECTRUM OF HUMAN VLDL shows increased ellipticity with decreasing temperature, which is completely reversible. We have found that the protein moieties of human VLDL and IDL contain substantially more helix (approximately 50%) than does that of human LDL.", "contents": "Secondary structure in very low density and intermediate density lipoproteins of human serum. We have studies the secondary structures of the protein moieties of very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL) of human serum by circular dichroism (CD). Two potential complications in the application of this technique to lipoproteins have been evaluated. First, using chronographic potentiometry in CD measurements of VLDL fractions of different mean particle diameters, we have analyzed statistically the CD signals in order to define the limits imposed by light scattering with respect to both particle diameter and wavelength. We found that CD measurements can be made to as low as 210 nm on particles of 520 A or smaller, and to 194 nm on particles of 450 A and below. Second, we have evaluated the CD contribution of lipid chromophores. Despite the high ratio of lipid to protein, the relative CD effect of the lipids is smaller than for low density lipoproteins (LDL). due to the extremely small ellipticity of natural VLDL triglycerides. Thus, CD measurements can be obtained with confidence on the preponderant bulk of normal VLDL. For the first time we report the CD spectra of human VLDL and IDL. In contrast with human LDL and the lipoproteins of the hypercholesterolemic rabbit, the entire CD SPECTRUM OF HUMAN VLDL shows increased ellipticity with decreasing temperature, which is completely reversible. We have found that the protein moieties of human VLDL and IDL contain substantially more helix (approximately 50%) than does that of human LDL."}
{"id": "PMID:222857", "title": "Apoprotein composition and turnover in rat intestinal lymph during steady-state triglyceride absorption.", "content": "Apoproteins of chylomicrons, very low density lipoprotein (VLDL), and a low density + high density fraction secreted by proximal and distal rat small intestine into mesenteric lymph were examined during triglyceride (TG) absorption. Apoprotein output and composition were determined and the turnover rates of labeled non-apoB (soluble) apoproteins in lipoprotein fractions were measured after an intraluminal [(3)H]leucine pulse during stable TG transport into lymph. The output of VLDL apoproteins exceeded that of chylomicrons during the absorption of 45 micro mol of TG per hour. More [(3)H]leucine was incorporated into VLDL than into chylomicrons and the decay of newly synthesized VLDL apoproteins was more rapid than that of chylomicrons, in part due to higher concentrations of apoA-I and apoA-IV with a rapid turnover rate. Chylomicrons from proximal intestine contained more apoA-I and less C peptides than chylomicrons from distal intestine. Ninety percent of [(3)H]leucine incorporated into soluble apoproteins was in apoA-I and apoA-IV, but little apoARP was labeled. The turnover rate of apoA-I and apoA-IV differed significantly in the lymph lipoproteins examined. Although total C peptide labeling was small, evidence for intestinal apoC-II formation and differing patterns of apoC-III subunit labeling was obtained. [(3)H]Leucine incorporation and apoprotein turnover rates in lipoprotein secreted by proximal and distal intestine were similar. The different turnover rates of apoA-I and apoA-IV in individual lipoproteins suggest that these A apoproteins are synthesized independently in the intestine.-Holt, P. R., A-L. Wu, and S. Bennett Clark. Apoprotein composition and turnover in rat intestinal lymph during steady-state triglyceride absorption.", "contents": "Apoprotein composition and turnover in rat intestinal lymph during steady-state triglyceride absorption. Apoproteins of chylomicrons, very low density lipoprotein (VLDL), and a low density + high density fraction secreted by proximal and distal rat small intestine into mesenteric lymph were examined during triglyceride (TG) absorption. Apoprotein output and composition were determined and the turnover rates of labeled non-apoB (soluble) apoproteins in lipoprotein fractions were measured after an intraluminal [(3)H]leucine pulse during stable TG transport into lymph. The output of VLDL apoproteins exceeded that of chylomicrons during the absorption of 45 micro mol of TG per hour. More [(3)H]leucine was incorporated into VLDL than into chylomicrons and the decay of newly synthesized VLDL apoproteins was more rapid than that of chylomicrons, in part due to higher concentrations of apoA-I and apoA-IV with a rapid turnover rate. Chylomicrons from proximal intestine contained more apoA-I and less C peptides than chylomicrons from distal intestine. Ninety percent of [(3)H]leucine incorporated into soluble apoproteins was in apoA-I and apoA-IV, but little apoARP was labeled. The turnover rate of apoA-I and apoA-IV differed significantly in the lymph lipoproteins examined. Although total C peptide labeling was small, evidence for intestinal apoC-II formation and differing patterns of apoC-III subunit labeling was obtained. [(3)H]Leucine incorporation and apoprotein turnover rates in lipoprotein secreted by proximal and distal intestine were similar. The different turnover rates of apoA-I and apoA-IV in individual lipoproteins suggest that these A apoproteins are synthesized independently in the intestine.-Holt, P. R., A-L. Wu, and S. Bennett Clark. Apoprotein composition and turnover in rat intestinal lymph during steady-state triglyceride absorption."}
{"id": "PMID:222858", "title": "The lipid composition of the electric organ of the ray, Torpedo marmorata, with specific reference to sulfatides and Na+-K+-ATPase.", "content": "The lipids from the electric organ of the ray, Torpedo marmorata, have been isolated and characterized. The major lipids were cholesterol, choline phospholipids, ethanolamine phospholipids, and sphingomyelins. The major fatty acids of ethanolamine phospholipids were 18:1, 18:0, 22:6, and 20:4. More than 50% of the acids in choline phospholipids were 16:0. The sphingomyelins consisted of five major ceramide species, all with sphingosine and the fatty acids 14:0, 15:0, 16:0, 22:1, and 24:1. The fatty acid 15:0 was mostly branched (n-2), a fatty acid earlier identified in sphingomyelins of the rectal gland of spiny dogfish. All long-chain bases were dihydroxy bases with a small percentage of branched chains. Sulfatides (cerebroside sulfate) made up the largest glycolipid fraction. The polar moiety wase galactose-3-sulfate. The fatty acids were normal and 2-hydroxy; the homologue 24:1 was the most abundant in both types of fatty acids. Most fatty acids were higher homologues of mono-unsaturated acids, but normal 18:0 fatty acid was also found. The long-chain bases were both dihydroxy and trihydroxy, with very small amounts of branched chains. The two major ceramide species of sulfatides were sphingosine combined with normal and hydroxy 24:1 fatty acids, respectively. Smaller amounts of trihydroxy base (18:0) were found linked to hydroxy 24:1 fatty acid, but not to its normal homologue. The cerebrosides contained the two major species mentioned above but lacked the trihydroxy base-hydroxy fatty acid species. The ratio of the activity of Na+-K+-dependent ATPase (EC 3.6.1.3) and the concentration of sulfatides was similar to ratios found for other tissues with normal and increased Na+ and K+ transporting capacity. The significance of this finding is discussed.", "contents": "The lipid composition of the electric organ of the ray, Torpedo marmorata, with specific reference to sulfatides and Na+-K+-ATPase. The lipids from the electric organ of the ray, Torpedo marmorata, have been isolated and characterized. The major lipids were cholesterol, choline phospholipids, ethanolamine phospholipids, and sphingomyelins. The major fatty acids of ethanolamine phospholipids were 18:1, 18:0, 22:6, and 20:4. More than 50% of the acids in choline phospholipids were 16:0. The sphingomyelins consisted of five major ceramide species, all with sphingosine and the fatty acids 14:0, 15:0, 16:0, 22:1, and 24:1. The fatty acid 15:0 was mostly branched (n-2), a fatty acid earlier identified in sphingomyelins of the rectal gland of spiny dogfish. All long-chain bases were dihydroxy bases with a small percentage of branched chains. Sulfatides (cerebroside sulfate) made up the largest glycolipid fraction. The polar moiety wase galactose-3-sulfate. The fatty acids were normal and 2-hydroxy; the homologue 24:1 was the most abundant in both types of fatty acids. Most fatty acids were higher homologues of mono-unsaturated acids, but normal 18:0 fatty acid was also found. The long-chain bases were both dihydroxy and trihydroxy, with very small amounts of branched chains. The two major ceramide species of sulfatides were sphingosine combined with normal and hydroxy 24:1 fatty acids, respectively. Smaller amounts of trihydroxy base (18:0) were found linked to hydroxy 24:1 fatty acid, but not to its normal homologue. The cerebrosides contained the two major species mentioned above but lacked the trihydroxy base-hydroxy fatty acid species. The ratio of the activity of Na+-K+-dependent ATPase (EC 3.6.1.3) and the concentration of sulfatides was similar to ratios found for other tissues with normal and increased Na+ and K+ transporting capacity. The significance of this finding is discussed."}
{"id": "PMID:222859", "title": "Lesions of the inferior alveolar nerve in sagittal osteotomy of the ramus -- experimental-study.", "content": "An experimental study on 30 hemimandibles in which sagittal osteotomy of the ramus was performed, after cleansing of the mandibular canal and filling it with wax, shows how inferior alveolar nerve lesions can occur. The use of a fine spatula is advocated for the splitting, in order to reduce the number of nerve lesions.", "contents": "Lesions of the inferior alveolar nerve in sagittal osteotomy of the ramus -- experimental-study. An experimental study on 30 hemimandibles in which sagittal osteotomy of the ramus was performed, after cleansing of the mandibular canal and filling it with wax, shows how inferior alveolar nerve lesions can occur. The use of a fine spatula is advocated for the splitting, in order to reduce the number of nerve lesions."}
{"id": "PMID:222860", "title": "Sialic acid content and growth control of mouse cells transformed by a temperature-sensitive mutant of SV40.", "content": "The sialic acid content of mouse cells transformed by a temperature-sensitive mutants (ts-mutant) of Simian virus 40 (SV40) was measured, and proved to be derived from changes in the sialic acid content in the plasma membrane which resulted from changes in the microsomal sialytransferase activity. Plasma membrane glycoproteins of ts-mutant transformed cells showed significantly different patterns on electrofocusing, but when treated with neuraminidase, differences of elution patterns were extinguished. It was concluded that there was a positive correlation between sialic acid content and loss of contact inhibition in the cell line examined.", "contents": "Sialic acid content and growth control of mouse cells transformed by a temperature-sensitive mutant of SV40. The sialic acid content of mouse cells transformed by a temperature-sensitive mutants (ts-mutant) of Simian virus 40 (SV40) was measured, and proved to be derived from changes in the sialic acid content in the plasma membrane which resulted from changes in the microsomal sialytransferase activity. Plasma membrane glycoproteins of ts-mutant transformed cells showed significantly different patterns on electrofocusing, but when treated with neuraminidase, differences of elution patterns were extinguished. It was concluded that there was a positive correlation between sialic acid content and loss of contact inhibition in the cell line examined."}
{"id": "PMID:222874", "title": "Chemotactic cell sorting in Dictyostelium discoideum.", "content": "We made mixed mounds of vitally stained prestalk cells and unstained prespore cells, from Dictyostelium discoideum (Dd), and exposed these to external 3',5'-cyclic-AMP (c-AMP) sources. We show that prestalk cells will sort out by moving directionally toward c-AMP sources held at less than 10(-5) M c-AMP. This is evidence for cell sorting via chemotaxis. We present arguments that the natural cell sorting, observed during Dd development, is also chemotactic to c-AMP.", "contents": "Chemotactic cell sorting in Dictyostelium discoideum. We made mixed mounds of vitally stained prestalk cells and unstained prespore cells, from Dictyostelium discoideum (Dd), and exposed these to external 3',5'-cyclic-AMP (c-AMP) sources. We show that prestalk cells will sort out by moving directionally toward c-AMP sources held at less than 10(-5) M c-AMP. This is evidence for cell sorting via chemotaxis. We present arguments that the natural cell sorting, observed during Dd development, is also chemotactic to c-AMP."}
{"id": "PMID:222875", "title": "Effect of cytochalasin B on the maturation of enveloped viruses.", "content": "The maturation of two enveloped viruses, influenza and vesicular stomatitis, occurs in cells treated with cytochalasin B. Virions produced in the presence of 50 microgram/ml cytochalasin B (CB) appear to be as infectious as those from control cells, indicating that polymerized actin is not required for the assembly of functional viral components. CB inhibits the release of influenza virus from treated cells, a phenomenon which appears to be a result of the synthesis of an aberrant neuraminidase (NA) glycoprotein; virions grown in CB-treated cells had a 90% reduction in specific enzymatic activity. We found that both influenza viral glycoproteins (NA and Hemagglutinin glycoprotein) had faster electrophoretic mobilities and were more heterogeneous in CB-treated cells as compared with controls. We also observed complete inhibition of incorporation of labeled glucosamine into viral glycoproteins in the presence of the drug. It was of interest that CB-induced inhibition of glycosylation appeared to cause loss of neuraminidase function, whereas hemagglutinating activity was not noticeably impaired. The presence of altered glycoproteins did not significantly diminish the infectivity of either influenza virus or vesicular stomatitis virus. Our results indicate that no step in the maturation of enveloped viruses is dependent upon an intact cytoskeletal network.", "contents": "Effect of cytochalasin B on the maturation of enveloped viruses. The maturation of two enveloped viruses, influenza and vesicular stomatitis, occurs in cells treated with cytochalasin B. Virions produced in the presence of 50 microgram/ml cytochalasin B (CB) appear to be as infectious as those from control cells, indicating that polymerized actin is not required for the assembly of functional viral components. CB inhibits the release of influenza virus from treated cells, a phenomenon which appears to be a result of the synthesis of an aberrant neuraminidase (NA) glycoprotein; virions grown in CB-treated cells had a 90% reduction in specific enzymatic activity. We found that both influenza viral glycoproteins (NA and Hemagglutinin glycoprotein) had faster electrophoretic mobilities and were more heterogeneous in CB-treated cells as compared with controls. We also observed complete inhibition of incorporation of labeled glucosamine into viral glycoproteins in the presence of the drug. It was of interest that CB-induced inhibition of glycosylation appeared to cause loss of neuraminidase function, whereas hemagglutinating activity was not noticeably impaired. The presence of altered glycoproteins did not significantly diminish the infectivity of either influenza virus or vesicular stomatitis virus. Our results indicate that no step in the maturation of enveloped viruses is dependent upon an intact cytoskeletal network."}
{"id": "PMID:222876", "title": "Mechanisms controlling choline transport and acetylcholine synthesis in motor nerve terminals during electrical stimulation.", "content": "Electrical stimulation of the chick ciliary nerve leads to a frequency-dependent increase in the Na+-dependent high affinity uptake of [3H]choline (SDHACU) and its conversion to acetylcholine (ACh) in the nerve terminals innervating the iris muscle. The forces that drive this choline (Ch) uptake across the presynaptic membrane were evaluated. Depolarization with increased [K+] out or veratridine decreases Ch accumulation. In addition to the electrical driving force, energy is provided by the Na+ gradient. Inhibition of the Na,K-ATPase decreased the Ch taken up. Thus, changes in the rate of Ch transport are dependent on the electrochemical gradients for both Ch and Na+. Ch uptake and ACh synthesis were increased after a conditioning preincubation with high [K+] out or veratridine. As is the case for electrical stimulation, this acceleration of Ch uptake and ACh synthesis was strongly dependent on the presence of Ca++ in the incubation medium. Na+ influx through a TTX-sensitive channel also contributed to this acceleration. Inasmuch as membrane depolarization reduces the initial velocity of Ch uptake and ACh synthesis, their increases during electrical stimulation therefore cannot be the direct effect of the depolarization phase of the action potential. Instead they are the result of the ionic fluxes accompanying the presynaptic spike. It is concluded that stimulation of Ch uptake and ACh synthesis by nerve activity depends first, on the ACh release elicited by Ca++ influx after depolarization and second, on the activation of the Na,K-ATPase due to Na+ entry. Furthermore, it is suggested that the release of ACh after stimulation drives translocation of cytoplasmic ACh into a protected compartment (probably vesicular). This recompartmentation of intraterminal ACh stimulates ACh synthesis by mass action, allowing further accumulation of Ch.", "contents": "Mechanisms controlling choline transport and acetylcholine synthesis in motor nerve terminals during electrical stimulation. Electrical stimulation of the chick ciliary nerve leads to a frequency-dependent increase in the Na+-dependent high affinity uptake of [3H]choline (SDHACU) and its conversion to acetylcholine (ACh) in the nerve terminals innervating the iris muscle. The forces that drive this choline (Ch) uptake across the presynaptic membrane were evaluated. Depolarization with increased [K+] out or veratridine decreases Ch accumulation. In addition to the electrical driving force, energy is provided by the Na+ gradient. Inhibition of the Na,K-ATPase decreased the Ch taken up. Thus, changes in the rate of Ch transport are dependent on the electrochemical gradients for both Ch and Na+. Ch uptake and ACh synthesis were increased after a conditioning preincubation with high [K+] out or veratridine. As is the case for electrical stimulation, this acceleration of Ch uptake and ACh synthesis was strongly dependent on the presence of Ca++ in the incubation medium. Na+ influx through a TTX-sensitive channel also contributed to this acceleration. Inasmuch as membrane depolarization reduces the initial velocity of Ch uptake and ACh synthesis, their increases during electrical stimulation therefore cannot be the direct effect of the depolarization phase of the action potential. Instead they are the result of the ionic fluxes accompanying the presynaptic spike. It is concluded that stimulation of Ch uptake and ACh synthesis by nerve activity depends first, on the ACh release elicited by Ca++ influx after depolarization and second, on the activation of the Na,K-ATPase due to Na+ entry. Furthermore, it is suggested that the release of ACh after stimulation drives translocation of cytoplasmic ACh into a protected compartment (probably vesicular). This recompartmentation of intraterminal ACh stimulates ACh synthesis by mass action, allowing further accumulation of Ch."}
{"id": "PMID:222877", "title": "Amplitude, kinetics, and reversibility of a light-induced decrease in guanosine 3',5'-cyclic monophosphate in frog photoreceptor membranes.", "content": "The concentration of guanosine 3',5'-cyclic monophosphate (cyclic GMP) has been examined in suspensions of freshly isolated frog rod outer segments using conditions which previously have been shown to maintain the ability of outer segments to perform a light-induced permeability change (presence of calf serum, anti-oxidant, and low calcium concentration). Illumination causes a rapid decrease in cyclic GMP levels which has a half-time approximately 125 ms. With light exposures that bleach less than 100 rhodopsin molecules in each rod outer segment, at least 10(4)-10(5) molecules of cyclic GMP are hydrolyzed for each rhodopsin molecule bleached. Half of the total cyclic GMP in each outer segment, approximately 2 X 10(7) molecules, is contained in the light-sensitive pool. If outer segments are exposed to continuous illumination, using intensities which bleach between 5.0 X 10(1) and 5.0 X 10(4) rhodopsin molecules/outer segment per second, cyclic GMP levels fall to a value characteristic for the intensity used. This suggests that a balance between synthesis and degradation of cyclic GMP is established. This constant level appears to be regulated by the rate of bleaching rhodopsin molecules (by the intensity of illumination), not the absolute number of rhodopsin molecules bleached...", "contents": "Amplitude, kinetics, and reversibility of a light-induced decrease in guanosine 3',5'-cyclic monophosphate in frog photoreceptor membranes. The concentration of guanosine 3',5'-cyclic monophosphate (cyclic GMP) has been examined in suspensions of freshly isolated frog rod outer segments using conditions which previously have been shown to maintain the ability of outer segments to perform a light-induced permeability change (presence of calf serum, anti-oxidant, and low calcium concentration). Illumination causes a rapid decrease in cyclic GMP levels which has a half-time approximately 125 ms. With light exposures that bleach less than 100 rhodopsin molecules in each rod outer segment, at least 10(4)-10(5) molecules of cyclic GMP are hydrolyzed for each rhodopsin molecule bleached. Half of the total cyclic GMP in each outer segment, approximately 2 X 10(7) molecules, is contained in the light-sensitive pool. If outer segments are exposed to continuous illumination, using intensities which bleach between 5.0 X 10(1) and 5.0 X 10(4) rhodopsin molecules/outer segment per second, cyclic GMP levels fall to a value characteristic for the intensity used. This suggests that a balance between synthesis and degradation of cyclic GMP is established. This constant level appears to be regulated by the rate of bleaching rhodopsin molecules (by the intensity of illumination), not the absolute number of rhodopsin molecules bleached..."}
{"id": "PMID:222878", "title": "Hindlimb extensor reflex of spinal rats given tranylcypromine stereoisomers.", "content": "The hindlimb extensor reflex of reserpinized, spinal rats was used to determine whether tranylcypromine (dl-TCP) and its stereoisomers (d-TCP and l-TCP) after tryptaminergic neurotransmission. dl-TCP and d-TCP caused an extensor reflex while l-TCP failed to cause a reliable extensor reflex. Neither H 22/54 nor nialamide affected the extensor reflex in rats given dl-TCP, while H 22/54 reduced the reflex in rats given d-TCP. The results suggest that dl-TCP and d-TCP have direct as well as indirect actions on tryptaminergic neurotransmission.", "contents": "Hindlimb extensor reflex of spinal rats given tranylcypromine stereoisomers. The hindlimb extensor reflex of reserpinized, spinal rats was used to determine whether tranylcypromine (dl-TCP) and its stereoisomers (d-TCP and l-TCP) after tryptaminergic neurotransmission. dl-TCP and d-TCP caused an extensor reflex while l-TCP failed to cause a reliable extensor reflex. Neither H 22/54 nor nialamide affected the extensor reflex in rats given dl-TCP, while H 22/54 reduced the reflex in rats given d-TCP. The results suggest that dl-TCP and d-TCP have direct as well as indirect actions on tryptaminergic neurotransmission."}
{"id": "PMID:222887", "title": "Boron betaine analogs: antitumor activity and effects on Ehrlich ascites tumor cell metabolism.", "content": "Several newly synthesized boron betaine analogs had antitumor activity in Ehrlich ascites, Walker 256 ascites carcinosarcoma, and Lewis lung screens and marginal activity in the B-16 melanotic melanoma screen. In vivo testing demonstrated that trimethylamine-cyanoborane inhibied Ehrlich ascites cell DNA and protein syntheses as well as gene modulation by chromatin protein phosphorylation and methylation. Trimethylamine-cyanoborane increased cyclic-AMP levels. In vitro testing showed that nuclear DNA polymerase, thymidylate synthetase, S-adenosylmethyltransferase, nonhistone chromatin methylation, deoxyribonuclease, ribonuclease, and cathepsin were inhibited by the boron analogs. These compounds did not demonstrate high antitumor activity at the doses employed, but blockage of methyl transfer from S-adenosylmethionine was established as a feasible method for controlling cell proliferation.", "contents": "Boron betaine analogs: antitumor activity and effects on Ehrlich ascites tumor cell metabolism. Several newly synthesized boron betaine analogs had antitumor activity in Ehrlich ascites, Walker 256 ascites carcinosarcoma, and Lewis lung screens and marginal activity in the B-16 melanotic melanoma screen. In vivo testing demonstrated that trimethylamine-cyanoborane inhibied Ehrlich ascites cell DNA and protein syntheses as well as gene modulation by chromatin protein phosphorylation and methylation. Trimethylamine-cyanoborane increased cyclic-AMP levels. In vitro testing showed that nuclear DNA polymerase, thymidylate synthetase, S-adenosylmethyltransferase, nonhistone chromatin methylation, deoxyribonuclease, ribonuclease, and cathepsin were inhibited by the boron analogs. These compounds did not demonstrate high antitumor activity at the doses employed, but blockage of methyl transfer from S-adenosylmethionine was established as a feasible method for controlling cell proliferation."}
{"id": "PMID:222888", "title": "Rheological and drug release properties of oil gels containing colloidal silicon dioxide.", "content": "The rheological properties of oil gels prepared by dispersing colloidal silica in n-dodecane and 1-dodecanol were examined. The differences in gel strength using these two media were accounted for by the difference in the extent of hydrogen bond formation between the silanol groups on the silica surface. The incorporation of methyl salicylate further modified the rheological properties of the gels. The drug was capable of hydrogen bonding with silanol groups in the n-dodecane gels, which increase gel strength at low concentrations; at high concentrations, the drug acted as a plasticizer. In 1-dodecanol systems, the drug acted solely as a plasticizer. Adsorption studies showed that methyl salicylate was adsorbed only on the silica particles in the n-dodecane medium. Interaction of the drug with the silanol groups in the n-dodecane systems did not appear to effect methyl salicylate release from the gels.", "contents": "Rheological and drug release properties of oil gels containing colloidal silicon dioxide. The rheological properties of oil gels prepared by dispersing colloidal silica in n-dodecane and 1-dodecanol were examined. The differences in gel strength using these two media were accounted for by the difference in the extent of hydrogen bond formation between the silanol groups on the silica surface. The incorporation of methyl salicylate further modified the rheological properties of the gels. The drug was capable of hydrogen bonding with silanol groups in the n-dodecane gels, which increase gel strength at low concentrations; at high concentrations, the drug acted as a plasticizer. In 1-dodecanol systems, the drug acted solely as a plasticizer. Adsorption studies showed that methyl salicylate was adsorbed only on the silica particles in the n-dodecane medium. Interaction of the drug with the silanol groups in the n-dodecane systems did not appear to effect methyl salicylate release from the gels."}
{"id": "PMID:222889", "title": "Antitumor agents. XXXV: Effects of brusatol, bruceoside A, and bruceantin on P-388 lymphocytic leukemia cell respiration.", "content": "Brusatol, a quassinoid with potent antineoplastic activity against P-388 lymphocytic leukemia cell proliferation, significantly inhibited P-388 cell hexokinase, phosphofructokinase, malic dehydrogenase, and succinic dehydrogenase. Mitochondrial oxidative phosphorylation, basal, and adenosine diphosphate-stimulated respiration, utilizing succinate and alpha-ketoglutarate as the substrate, was suppressed significantly by in vivo treatment with brusatol. However, brusatol treatment had no effect on liver oxidative phosphorylation. Brusatol greatly increased P-388 cyclic AMP levels but had no effect on liver cyclic nucleotides. Similar inhibitory effects on P-388 cell oxidative phosphorylation were found in vitro with brusatol, bruceoside A, and bruceantin. Brusatol had no effect on adenosine triphosphatase activity or on uncoupling of oxidative phosphorylation. Rather, brusatol appeared to increase the concentration of reduced mitochondrial electron-transport cofactors, thereby blocking aerobic respiration. A proposed mechanism of action is discussed.", "contents": "Antitumor agents. XXXV: Effects of brusatol, bruceoside A, and bruceantin on P-388 lymphocytic leukemia cell respiration. Brusatol, a quassinoid with potent antineoplastic activity against P-388 lymphocytic leukemia cell proliferation, significantly inhibited P-388 cell hexokinase, phosphofructokinase, malic dehydrogenase, and succinic dehydrogenase. Mitochondrial oxidative phosphorylation, basal, and adenosine diphosphate-stimulated respiration, utilizing succinate and alpha-ketoglutarate as the substrate, was suppressed significantly by in vivo treatment with brusatol. However, brusatol treatment had no effect on liver oxidative phosphorylation. Brusatol greatly increased P-388 cyclic AMP levels but had no effect on liver cyclic nucleotides. Similar inhibitory effects on P-388 cell oxidative phosphorylation were found in vitro with brusatol, bruceoside A, and bruceantin. Brusatol had no effect on adenosine triphosphatase activity or on uncoupling of oxidative phosphorylation. Rather, brusatol appeared to increase the concentration of reduced mitochondrial electron-transport cofactors, thereby blocking aerobic respiration. A proposed mechanism of action is discussed."}
{"id": "PMID:222890", "title": "Phosphodiesterase inhibition by succinic and related acid biphenylalkyl monoesters.", "content": "Biphenylalkyl monoesters of succinic and related acids represent a potent new class of cyclic AMP phosphodiesterase inhibitors. The biphenyl group is necessary for potent inhibition. The spatial relationship of the carboxyl and ester groups and alkyl chain length are important to inhibitory potency.", "contents": "Phosphodiesterase inhibition by succinic and related acid biphenylalkyl monoesters. Biphenylalkyl monoesters of succinic and related acids represent a potent new class of cyclic AMP phosphodiesterase inhibitors. The biphenyl group is necessary for potent inhibition. The spatial relationship of the carboxyl and ester groups and alkyl chain length are important to inhibitory potency."}
{"id": "PMID:222892", "title": "Electroencephalographic and behavioral tolerance to and cross-tolerance between D-Ala2-methionine-enkephalinamide and morphine in the rat.", "content": "Rats were given repeated intraventricular (i.vt.) injections of D-enkephalin (20 microgram/4 hr) or morphine (20 microgram/4 hr) for 72 to 96 hr during electroencephalograman(EEG) recording. Initial epileptiform EEG and associated wet-dog shakes occurred following D-enkephalin but not morphine. The epileptoid EEG progressed to a continous high-voltage EEG synchrony similar to morphine and was associated with behavioral stupor. Rapid eye movement sleep was also suppressed. Repeated administration of D-enkephalin or morphine produced tolerance to their effects. When challenged with i.vt. morphine, D-enkephalin-tolerant rats were cross-tolerant to morphine. Likewise, morphine-tolerant rats were cross-tolerant to D-enkephalin. While the morphine-tolerant rats demonstrated a marked abstinence syndrome when challenged with naloxone (10 mg/kg i.p.), no abstinence signs were observed in the D-enkephalin-tolerant rats. The demonstration of tolerance and cross-tolerance between morphine and D-enkephalin suggests a similar mechanism of action, but the differential development of physical dependence may entail different mechanisms or receptor sensitivities for this effect. These findings of similarities and differences in the acute and chronic effects of D-enkephalin and morphine support the contention that heterogenous opiate receptors may mediate their pharmacologic actions.", "contents": "Electroencephalographic and behavioral tolerance to and cross-tolerance between D-Ala2-methionine-enkephalinamide and morphine in the rat. Rats were given repeated intraventricular (i.vt.) injections of D-enkephalin (20 microgram/4 hr) or morphine (20 microgram/4 hr) for 72 to 96 hr during electroencephalograman(EEG) recording. Initial epileptiform EEG and associated wet-dog shakes occurred following D-enkephalin but not morphine. The epileptoid EEG progressed to a continous high-voltage EEG synchrony similar to morphine and was associated with behavioral stupor. Rapid eye movement sleep was also suppressed. Repeated administration of D-enkephalin or morphine produced tolerance to their effects. When challenged with i.vt. morphine, D-enkephalin-tolerant rats were cross-tolerant to morphine. Likewise, morphine-tolerant rats were cross-tolerant to D-enkephalin. While the morphine-tolerant rats demonstrated a marked abstinence syndrome when challenged with naloxone (10 mg/kg i.p.), no abstinence signs were observed in the D-enkephalin-tolerant rats. The demonstration of tolerance and cross-tolerance between morphine and D-enkephalin suggests a similar mechanism of action, but the differential development of physical dependence may entail different mechanisms or receptor sensitivities for this effect. These findings of similarities and differences in the acute and chronic effects of D-enkephalin and morphine support the contention that heterogenous opiate receptors may mediate their pharmacologic actions."}
{"id": "PMID:222896", "title": "Sodium ions, acting at high-affinity extracellular sites, inhibit sodium-ATPase activity of the sodium pump by slowing dephosphorylation.", "content": "1. It is known that extracellular Na+ ions, in low concentrations, inhibit Na+-ATPase activity in resealed red cell ghosts and that this inhibition is reversed by high concentrations of extracellular Na+. We have attempted to elucidate these actions of extracellular Na+ by investigating the dependence on Na+ concentration of (a) ATP-ADP exchange and Na+-ATPase activity both in native and in N-ethylmaleimide (NEM)-treated (Na+ + K+)-ATPase from pig kidney, and (b) the rate of hydrolysis of the phosphorylated kidney enzyme in the absence of K+ ions. 2. With the native enzyme, ATP-ADP exchange and Na+-ATPase activity showed similar responses to changes in Na+ concentration: a steep but S-shaped rise between 0 and 2.5 mM, a slight fall (exchange) or a plateau (ATPase) between 2.5 and 10 mM, and a roughly linear rise between 10 and 150 mM. With NEM-treated enzyme, the ATP-ADP exchange, which was greatly accelerated, showed no sign either of inhibition at intermediate Na+ concentrations or of the reversal of that inhibition at higher concentrations. The exchange rate increased with Na+ concentration in a smooth curve and was half-maximal at about 7 mM. 3. The effects, on ATP-ADP exchange, of changing the concentrations of ATP, ADP and Mg have also been investigated. With both native and NEM-treated enzyme, the interactions of ATP, ADP and Mg are complicated; they show that, for the reaction leading to ATP formation, either free ADP rather than MgADP is the substrate, or Mg2+ ions are inhibitory (or both). 4. Since NEM, in the conditions in which we have used it, is believed to act by inhibiting the conversion of an ADP-sensitive form of the phosphoenzyme (E1P) to an ADP-insensitive form (E2P), the absence of Na+ inhibition of ATP-ADP exchange in NEM-treated enzyme, together with the parallel effects of Na+ ions on the ATP-ADP exchange activity and on the Na+-ATPase activity of native enzyme, suggests that the inhibitory effect of external Na+ occurs after the conversion of E1P into E2P. 5. To test whether this inhibitory effect of Na+ reflected inhibition of the hydrolysis of E2P, we measured the rate of loss of incorporated 32P when enzyme, newly phosphorylated by [gamma32P]ATP, was squirted into a large volume of ice-cold solution containing 1,2-cyclohexylenedinitrilotetraacetic aicd (CDTA), unlabelled ATP and 0, 5 or 150 mM-Na+. The rate of loss of radioactivity from the membranes was least at 5 mM-Na+, about twice as great at 150 mM-Na+, and about 5 times as great at 20 microM (final) Na+. 6. An unexpected feature of the results was that the pattern of stimulation of ATP-ADP exchange in intact cells. If Na+ ions are absent externally, a different could be fitted better on the assumption that activation by internal Na+ occurs at two sites with equal affinities, than on the assumptions that activation occurs at a single site or at three sites with equal affinities.", "contents": "Sodium ions, acting at high-affinity extracellular sites, inhibit sodium-ATPase activity of the sodium pump by slowing dephosphorylation. 1. It is known that extracellular Na+ ions, in low concentrations, inhibit Na+-ATPase activity in resealed red cell ghosts and that this inhibition is reversed by high concentrations of extracellular Na+. We have attempted to elucidate these actions of extracellular Na+ by investigating the dependence on Na+ concentration of (a) ATP-ADP exchange and Na+-ATPase activity both in native and in N-ethylmaleimide (NEM)-treated (Na+ + K+)-ATPase from pig kidney, and (b) the rate of hydrolysis of the phosphorylated kidney enzyme in the absence of K+ ions. 2. With the native enzyme, ATP-ADP exchange and Na+-ATPase activity showed similar responses to changes in Na+ concentration: a steep but S-shaped rise between 0 and 2.5 mM, a slight fall (exchange) or a plateau (ATPase) between 2.5 and 10 mM, and a roughly linear rise between 10 and 150 mM. With NEM-treated enzyme, the ATP-ADP exchange, which was greatly accelerated, showed no sign either of inhibition at intermediate Na+ concentrations or of the reversal of that inhibition at higher concentrations. The exchange rate increased with Na+ concentration in a smooth curve and was half-maximal at about 7 mM. 3. The effects, on ATP-ADP exchange, of changing the concentrations of ATP, ADP and Mg have also been investigated. With both native and NEM-treated enzyme, the interactions of ATP, ADP and Mg are complicated; they show that, for the reaction leading to ATP formation, either free ADP rather than MgADP is the substrate, or Mg2+ ions are inhibitory (or both). 4. Since NEM, in the conditions in which we have used it, is believed to act by inhibiting the conversion of an ADP-sensitive form of the phosphoenzyme (E1P) to an ADP-insensitive form (E2P), the absence of Na+ inhibition of ATP-ADP exchange in NEM-treated enzyme, together with the parallel effects of Na+ ions on the ATP-ADP exchange activity and on the Na+-ATPase activity of native enzyme, suggests that the inhibitory effect of external Na+ occurs after the conversion of E1P into E2P. 5. To test whether this inhibitory effect of Na+ reflected inhibition of the hydrolysis of E2P, we measured the rate of loss of incorporated 32P when enzyme, newly phosphorylated by [gamma32P]ATP, was squirted into a large volume of ice-cold solution containing 1,2-cyclohexylenedinitrilotetraacetic aicd (CDTA), unlabelled ATP and 0, 5 or 150 mM-Na+. The rate of loss of radioactivity from the membranes was least at 5 mM-Na+, about twice as great at 150 mM-Na+, and about 5 times as great at 20 microM (final) Na+. 6. An unexpected feature of the results was that the pattern of stimulation of ATP-ADP exchange in intact cells. If Na+ ions are absent externally, a different could be fitted better on the assumption that activation by internal Na+ occurs at two sites with equal affinities, than on the assumptions that activation occurs at a single site or at three sites with equal affinities."}
{"id": "PMID:222897", "title": "Dual innervation of end-plate sites and its consequences for neuromuscular transmission in muscles of adult Xenopus laevis.", "content": "1. Electrophysiological study of dually innervated end-plate sites was carried out in Xenopus laevis pectoral muscle fibres. End-plate potentials (e.p.p.s) and miniature end-plate potentials (m.e.p.p.s) have been recorded in Mg-blocked preparations. 2. The mean quantal content (m) of each e.p.p. at dually innervated end-plates was significantly smaller than the corresponding values obtained at singly innervated ones. At a given doubly innervated end-plate site the values of m tended to be inversely related, so that the compound value of m (obtained by adding them) was in the same range as that found in singly innervated junctions. These findings were taken to suggest the existence of an upper limit in the average amount of transmitter released at a synaptic site. 3. It was found that neither intermittent presynaptic conduction block, nor particular muscle fibre properties could account for the low values of m in dual end plates. The small size of the nerve terminals appears to be the most likely explanation. 4. The sensitivity to acetylcholine and muscle fibre electrical properties were investigated; no differences were found between fibres with sub- or suprathreshold e.p.p.s. 5. The nature of the factors responsible for this presumed small size of the nerve endings (competition between nerve endings for a limited synaptic space on the muscle membrane or reciprocal interaction between closely located terminals) as well as the possible origins of polyinnervation are discussed.", "contents": "Dual innervation of end-plate sites and its consequences for neuromuscular transmission in muscles of adult Xenopus laevis. 1. Electrophysiological study of dually innervated end-plate sites was carried out in Xenopus laevis pectoral muscle fibres. End-plate potentials (e.p.p.s) and miniature end-plate potentials (m.e.p.p.s) have been recorded in Mg-blocked preparations. 2. The mean quantal content (m) of each e.p.p. at dually innervated end-plates was significantly smaller than the corresponding values obtained at singly innervated ones. At a given doubly innervated end-plate site the values of m tended to be inversely related, so that the compound value of m (obtained by adding them) was in the same range as that found in singly innervated junctions. These findings were taken to suggest the existence of an upper limit in the average amount of transmitter released at a synaptic site. 3. It was found that neither intermittent presynaptic conduction block, nor particular muscle fibre properties could account for the low values of m in dual end plates. The small size of the nerve terminals appears to be the most likely explanation. 4. The sensitivity to acetylcholine and muscle fibre electrical properties were investigated; no differences were found between fibres with sub- or suprathreshold e.p.p.s. 5. The nature of the factors responsible for this presumed small size of the nerve endings (competition between nerve endings for a limited synaptic space on the muscle membrane or reciprocal interaction between closely located terminals) as well as the possible origins of polyinnervation are discussed."}
{"id": "PMID:222898", "title": "The physiology, pharmacology, and trophic effectiveness of synapses formed by autonomic preganglionic nerves on frog skeletal muscle.", "content": "1. Frog sartorius muscles, newly denervated and transplanted to the lymph sac of the back, are reinnervated by implanted cholinergic nerves (spinal somatic motor nerves or the preganglionic sympathetic splanchnic nerve), but not by nerves). 2. Foreign somatic motor nerves (s.m.n.s) form synapses that resemble normal sartorius neuromuscular junctions electrophysiologically. 3. Axons of the sympathetic preganglionic splanchnic nerve (s.p.n.) grow throughout the muscle, but only a small percentage of fibres form synapses. Most e.p.p.s are of low quantal content, generally subthreshold. Long onset latencies and multiple post-synaptic responses indicate that innervation is multiple, multi-terminal, and by unmyelinated axons. 4. Spontaneous miniature e.p.p.s at splanchnic junctions occur at an average rate under 0.1/sec. Their average amplitude and time course are about the same as for control muscles, but the variability of amplitudes is greater than for control muscles. 5. The amount of facilitation shown by s.p.n.-evoked e.p.p.s is the same as by s.m.n. e.p.p.s, but the time course is almost twice as long. 6. S.p.n.-reinnervated fibres show dramatic post-tetanic potentiation preceded by depression, following as few as 20--50 stimuli. 7. As judged by standard physiological and histochemical criteria, AChEsterase is absent at s.p.n. junctions. 8. The pharmacological responses of the s.p.n. junctions are similar to those of normal or foreign s.m.n. innervated neuromuscular junctions in their sensitivity to the cholinergic blocking agents D-tubocurarine and hexamethonium. 9 The s.p.n. is capable of restricting ACh sensitivity to the sites of nerve contacts, although this restriction occurs more slowly and less completely than with s.m.n. reinnervation. The loss of extrajunctional ACh sensitivity can be correlated with effectiveness of innervation; but significant restriction occurs even in s.p.n. reinnervated fibres that probably never contract to nerve stimulation.", "contents": "The physiology, pharmacology, and trophic effectiveness of synapses formed by autonomic preganglionic nerves on frog skeletal muscle. 1. Frog sartorius muscles, newly denervated and transplanted to the lymph sac of the back, are reinnervated by implanted cholinergic nerves (spinal somatic motor nerves or the preganglionic sympathetic splanchnic nerve), but not by nerves). 2. Foreign somatic motor nerves (s.m.n.s) form synapses that resemble normal sartorius neuromuscular junctions electrophysiologically. 3. Axons of the sympathetic preganglionic splanchnic nerve (s.p.n.) grow throughout the muscle, but only a small percentage of fibres form synapses. Most e.p.p.s are of low quantal content, generally subthreshold. Long onset latencies and multiple post-synaptic responses indicate that innervation is multiple, multi-terminal, and by unmyelinated axons. 4. Spontaneous miniature e.p.p.s at splanchnic junctions occur at an average rate under 0.1/sec. Their average amplitude and time course are about the same as for control muscles, but the variability of amplitudes is greater than for control muscles. 5. The amount of facilitation shown by s.p.n.-evoked e.p.p.s is the same as by s.m.n. e.p.p.s, but the time course is almost twice as long. 6. S.p.n.-reinnervated fibres show dramatic post-tetanic potentiation preceded by depression, following as few as 20--50 stimuli. 7. As judged by standard physiological and histochemical criteria, AChEsterase is absent at s.p.n. junctions. 8. The pharmacological responses of the s.p.n. junctions are similar to those of normal or foreign s.m.n. innervated neuromuscular junctions in their sensitivity to the cholinergic blocking agents D-tubocurarine and hexamethonium. 9 The s.p.n. is capable of restricting ACh sensitivity to the sites of nerve contacts, although this restriction occurs more slowly and less completely than with s.m.n. reinnervation. The loss of extrajunctional ACh sensitivity can be correlated with effectiveness of innervation; but significant restriction occurs even in s.p.n. reinnervated fibres that probably never contract to nerve stimulation."}
{"id": "PMID:222899", "title": "Competitive interaction between foreign nerves innervating frog skeletal muscle.", "content": "1. Competition between two foreign nerves innervating frog skeletal muscle has been studied by using pairs of somatic motor nerves (s.m.n.s) or one s.m.n. and the preganglionic splanchnic nerve (s.p.n.) implanted into a denervated sartorius muscle that has been transplanted to the lymph sac of the back. 2. A single s.m.n. implanted into the muscle succeeded in innervating essentially every fibre within 2--3 months; tetanic stimulation of the nerve elicited 9--100% of the maximal direct tetanus tension. Most of the e.p.p.s were suprathreshold, since a single indirect stimulus evoked a twitch 60--100% as large as that to a direct stimulus. 3. If two s.m.n.s were implanted simultaneously, tetanic stimulation of either elicited 80--100% of the maximal tension to direct stimulation. If one nerve was implanted 2--3 months before the other, the second, although usually less effective than the first, normally innervated 50--100% of the fibres, with approximately the same time course of innervation as a single s.m.n. 4. Mutual synaptic repression was seen on examination of twitch tensions. With either simultaneous or staggered innervation, stimulation of each s.m.n. resulted in a twitch of 30--50% of the total direct twitch tension, with little overlap between the fields driven by the two nerves. Intracellular recordings showed that the distribution of subthreshold and spike-producing e.p.p.s reflected the existence of separate twitch fields. Even if one s.m.n. was implanted several months before the other and had time to establish suprathreshold junctions on most muscle fibres, an s.m.n. implanted later was able to reduce sharply the effectiveness of many junctions from the earlier nerve while itself innervating most muscle fibres. 5. The subthreshold e.p.p.s had low quantal content, typically ten or fewer quanta/e.p.p. The min e.p.p. frequency was very low, while min e.p.p. amplitude appeared to be normal. 6. In the vast majority of muscle fibres, junctions from the two nerves were not within recording distance of each other. Hence, we infer that the competitive interaction was mediated somehow via the muscle fibre. 7. The preganglionic splanchnic nerve, which also successfully reinnervated frog skeletal muscle, competed with a foreign s.m.n. in ways which differ qualitatively from the competition by a second s.m.n. In the presence of a s.m.n., synapses of the s.p.n. were almost universally subthreshold. However, if the s.p.n. was implanted 2--3 months before the s.m.n., the s.m.n. was prevented for several months from innervating fibres driven by the s.p.n. This delay in s.m.n. reinnervation was greater than if the first nerve implanted was also an s.m.n. 8. After 6--8 months of dual innervation by s.m.n. and s.p.n., the s.m.n. became almost totally dominant. However, if the s.m.n. was then sectioned, the s.p.n. became as effective, within approximately 1 week, as it would have been in the absence of the s.m.n.", "contents": "Competitive interaction between foreign nerves innervating frog skeletal muscle. 1. Competition between two foreign nerves innervating frog skeletal muscle has been studied by using pairs of somatic motor nerves (s.m.n.s) or one s.m.n. and the preganglionic splanchnic nerve (s.p.n.) implanted into a denervated sartorius muscle that has been transplanted to the lymph sac of the back. 2. A single s.m.n. implanted into the muscle succeeded in innervating essentially every fibre within 2--3 months; tetanic stimulation of the nerve elicited 9--100% of the maximal direct tetanus tension. Most of the e.p.p.s were suprathreshold, since a single indirect stimulus evoked a twitch 60--100% as large as that to a direct stimulus. 3. If two s.m.n.s were implanted simultaneously, tetanic stimulation of either elicited 80--100% of the maximal tension to direct stimulation. If one nerve was implanted 2--3 months before the other, the second, although usually less effective than the first, normally innervated 50--100% of the fibres, with approximately the same time course of innervation as a single s.m.n. 4. Mutual synaptic repression was seen on examination of twitch tensions. With either simultaneous or staggered innervation, stimulation of each s.m.n. resulted in a twitch of 30--50% of the total direct twitch tension, with little overlap between the fields driven by the two nerves. Intracellular recordings showed that the distribution of subthreshold and spike-producing e.p.p.s reflected the existence of separate twitch fields. Even if one s.m.n. was implanted several months before the other and had time to establish suprathreshold junctions on most muscle fibres, an s.m.n. implanted later was able to reduce sharply the effectiveness of many junctions from the earlier nerve while itself innervating most muscle fibres. 5. The subthreshold e.p.p.s had low quantal content, typically ten or fewer quanta/e.p.p. The min e.p.p. frequency was very low, while min e.p.p. amplitude appeared to be normal. 6. In the vast majority of muscle fibres, junctions from the two nerves were not within recording distance of each other. Hence, we infer that the competitive interaction was mediated somehow via the muscle fibre. 7. The preganglionic splanchnic nerve, which also successfully reinnervated frog skeletal muscle, competed with a foreign s.m.n. in ways which differ qualitatively from the competition by a second s.m.n. In the presence of a s.m.n., synapses of the s.p.n. were almost universally subthreshold. However, if the s.p.n. was implanted 2--3 months before the s.m.n., the s.m.n. was prevented for several months from innervating fibres driven by the s.p.n. This delay in s.m.n. reinnervation was greater than if the first nerve implanted was also an s.m.n. 8. After 6--8 months of dual innervation by s.m.n. and s.p.n., the s.m.n. became almost totally dominant. However, if the s.m.n. was then sectioned, the s.p.n. became as effective, within approximately 1 week, as it would have been in the absence of the s.m.n."}
{"id": "PMID:222901", "title": "Estrogen-progesterone therapy in perimenopausal women.", "content": "A retrospective study was made of 74 women who had received estrogen continuously, cycled with progesterone, for menopausal symptoms over an average 57-month period. Treated patients were compared with control patients from the same private practice. Vabra endometrial aspiration biopsies showed no statistical differences between 25 treated and 28 untreated patients in the frequency of normal, inactive, hyperplastic or neoplastic specimens. The most common finding in the treated group was a secretory response, which suggests that progesterone exerts an antiestrogen effect even when estrogen is given on a continuing basis. There is evidence that the vaginal maturation index in the postmenopausal patient, although helpful in determining the current state of her systemic estrogen activity, may not reflect the effect of estrogen on the endometrium. Estrogen therapy has no absolute predictable correlation with endometrial histology. Thus, the information from routine endometrial curettage is essential to evaluate the status of all treated patients. Among all hormone-treated patients (74), weight decreased over time, blood pressure, blood sugar and cholesterol levels were relatively unchanged, and Papanicolaou smear classes improved.", "contents": "Estrogen-progesterone therapy in perimenopausal women. A retrospective study was made of 74 women who had received estrogen continuously, cycled with progesterone, for menopausal symptoms over an average 57-month period. Treated patients were compared with control patients from the same private practice. Vabra endometrial aspiration biopsies showed no statistical differences between 25 treated and 28 untreated patients in the frequency of normal, inactive, hyperplastic or neoplastic specimens. The most common finding in the treated group was a secretory response, which suggests that progesterone exerts an antiestrogen effect even when estrogen is given on a continuing basis. There is evidence that the vaginal maturation index in the postmenopausal patient, although helpful in determining the current state of her systemic estrogen activity, may not reflect the effect of estrogen on the endometrium. Estrogen therapy has no absolute predictable correlation with endometrial histology. Thus, the information from routine endometrial curettage is essential to evaluate the status of all treated patients. Among all hormone-treated patients (74), weight decreased over time, blood pressure, blood sugar and cholesterol levels were relatively unchanged, and Papanicolaou smear classes improved."}
{"id": "PMID:222902", "title": "Familial respiratory distress syndrome in three consecutive full-term infants. Case reports and documentation of lung enzyme activities.", "content": "Familial respiratory distress syndrome in full-term newborn infants is a rare occurrence. Our patient delivered three consecutive full-term infants who developed findings consistent with respiratory distress syndrome. All three died from autopsy-proven hyaline membrane disease. Analysis of the activities of four enzymes that play an important role in the biosynthesis of lecithin (choline kinase, choline phosphotransferase, phospholipase A and lysolecithin acyltransferase) failed to disclose an abnormality in lung samples in our patient with familial respiratory distress syndrome.", "contents": "Familial respiratory distress syndrome in three consecutive full-term infants. Case reports and documentation of lung enzyme activities. Familial respiratory distress syndrome in full-term newborn infants is a rare occurrence. Our patient delivered three consecutive full-term infants who developed findings consistent with respiratory distress syndrome. All three died from autopsy-proven hyaline membrane disease. Analysis of the activities of four enzymes that play an important role in the biosynthesis of lecithin (choline kinase, choline phosphotransferase, phospholipase A and lysolecithin acyltransferase) failed to disclose an abnormality in lung samples in our patient with familial respiratory distress syndrome."}
{"id": "PMID:222906", "title": "Antiviral activity of aliphatic nucleoside analogues: structure-function relationship.", "content": "Of a series of 58 aliphatic nucleoside analogues, (S)-9-(2,3-dihydroxypropyl)adenine [(S)-DHPA] proved to be the most active congener, when assayed for antiviral activity in primary rabbit kidney cell cultures challenged with either vaccinia or vesicular stomatitis virus. Whereas most analogues derived from substituted purine and pyrimidine bases and bearing various hydroxy- or amino-substituted alkyl chains did not show evidence of antiviral activity at a concentration of 2 mM, (S)-DHPA inhibited both vaccinia and vesicular stomatitis virus replication at 0.05-0.1 mM. For 9-[(RS)-2,3-diazidopropyl]adenine and some di- and trihydroxybutyl analogues of DHPA, viz., 9-[(2RS,3SR)-2,3-dihydroxybutylladenine, 9-[(RS)- or 9-[(S)-3,4-dihydroxybutyl]adenine, 9-[(2S,3R)-2,3,4-trihydroxybutyl]adenine, and 3-(adenin-9-yl)-(RS)-alanine, an antiviral effect was noted at a concentration of 0.5-1 mM.", "contents": "Antiviral activity of aliphatic nucleoside analogues: structure-function relationship. Of a series of 58 aliphatic nucleoside analogues, (S)-9-(2,3-dihydroxypropyl)adenine [(S)-DHPA] proved to be the most active congener, when assayed for antiviral activity in primary rabbit kidney cell cultures challenged with either vaccinia or vesicular stomatitis virus. Whereas most analogues derived from substituted purine and pyrimidine bases and bearing various hydroxy- or amino-substituted alkyl chains did not show evidence of antiviral activity at a concentration of 2 mM, (S)-DHPA inhibited both vaccinia and vesicular stomatitis virus replication at 0.05-0.1 mM. For 9-[(RS)-2,3-diazidopropyl]adenine and some di- and trihydroxybutyl analogues of DHPA, viz., 9-[(2RS,3SR)-2,3-dihydroxybutylladenine, 9-[(RS)- or 9-[(S)-3,4-dihydroxybutyl]adenine, 9-[(2S,3R)-2,3,4-trihydroxybutyl]adenine, and 3-(adenin-9-yl)-(RS)-alanine, an antiviral effect was noted at a concentration of 0.5-1 mM."}
{"id": "PMID:222907", "title": "Cardenolide analogues. 4. (20R)- and (20S)-Cardanolides: on the roles of the 20(22)-ene and 14beta-hydroxyl in genin activity.", "content": "(20R)-20,22-Dihydrodigitoxigenin (3a) and (20S)-20,22-dihydrodigitoxigenin (3b) were isolated from (20R,S)-20,22-dihydrodigitoxigenin (3) by three fractional crystallizations each from ethyl acetate. The two diastereomers have distinct NMR spectra and similar (Na+,K+)ATPase inhibitory activities (I50 = 1.1-1.4 X 10(-5) M)--about 1/100 as active as digitoxigenin (1). Their activity compared with other cardenolide analogues suggests a passive geometric role for the 20(22) double bond in eliciting (Na+,K+)ATPase inhibition, keeping the lactone carbonyl in the proper orientation. (20S)-3 beta,14 beta-Dihydroxy-22-methylene-5 beta,14 beta-cardanolide (7a) was then synthesized from 3a, and (20R)-3 beta,14 beta-dihydroxy-22-methylene-5 beta,14 beta-cardanolide (7b) from 3b. They were found to be equivalently active in inhibiting (Na+,K+)ATPase, with I50 values of 7.0 x 10(-5) M. Although it has been usually believed that the 14 beta-hydroxyl of cardenolides increases binding to the receptor, 2b (the 14-ene derivative of 7b) was more than twice as active (I50 = 3.0 X 10(-5)) than either 7a or 7b.", "contents": "Cardenolide analogues. 4. (20R)- and (20S)-Cardanolides: on the roles of the 20(22)-ene and 14beta-hydroxyl in genin activity. (20R)-20,22-Dihydrodigitoxigenin (3a) and (20S)-20,22-dihydrodigitoxigenin (3b) were isolated from (20R,S)-20,22-dihydrodigitoxigenin (3) by three fractional crystallizations each from ethyl acetate. The two diastereomers have distinct NMR spectra and similar (Na+,K+)ATPase inhibitory activities (I50 = 1.1-1.4 X 10(-5) M)--about 1/100 as active as digitoxigenin (1). Their activity compared with other cardenolide analogues suggests a passive geometric role for the 20(22) double bond in eliciting (Na+,K+)ATPase inhibition, keeping the lactone carbonyl in the proper orientation. (20S)-3 beta,14 beta-Dihydroxy-22-methylene-5 beta,14 beta-cardanolide (7a) was then synthesized from 3a, and (20R)-3 beta,14 beta-dihydroxy-22-methylene-5 beta,14 beta-cardanolide (7b) from 3b. They were found to be equivalently active in inhibiting (Na+,K+)ATPase, with I50 values of 7.0 x 10(-5) M. Although it has been usually believed that the 14 beta-hydroxyl of cardenolides increases binding to the receptor, 2b (the 14-ene derivative of 7b) was more than twice as active (I50 = 3.0 X 10(-5)) than either 7a or 7b."}
{"id": "PMID:222909", "title": "Studies on the mechanism of antiviral action of 1-(beta-D-ribofuranosyl)-1,2,4-triazole-3-carboxamide (ribavirin).", "content": "Syntheses are described for the 5'-phosphates of the 2'- and 3'-O-methylribavirins (2a and 2b) and the methyl ester of ribavirin 5'-phosphate (3). The 5'-phosphate of 1-beta-(D-ribofuranosyl)-1,2,4-triazole (2d) was obtained via the 3-carboxyl derivative of ribavirin 5'-phosphate (2c). Compounds 2a, 2b, and 2d were inactive as inactive as inhibitors of IMP dehydrogenase under conditions where the parent ribavirin 5'-phosphate (2) was an effective inhibitor. Weak inhibitory activity was exhibited by 3 (Ki approximately 200 muM) and 2c (K1 approximately 70 muM). Under conditions where ribavirin (1) is effectively phosphorylated by rat liver nucleoside kinase, the 2'- and 3'-O-methylribavirins (1a and 1b), the 3-carboxylate of ribavirin (1c), and the riboside of 1,2,4-triazole (1d) were totally inactive. The overall results are fully consistent with the lack of antiviral activity of 1a and 1b, while the specificity of ribavirin as an antiviral agent is further underlined by the behavior of the methyl ester 3.", "contents": "Studies on the mechanism of antiviral action of 1-(beta-D-ribofuranosyl)-1,2,4-triazole-3-carboxamide (ribavirin). Syntheses are described for the 5'-phosphates of the 2'- and 3'-O-methylribavirins (2a and 2b) and the methyl ester of ribavirin 5'-phosphate (3). The 5'-phosphate of 1-beta-(D-ribofuranosyl)-1,2,4-triazole (2d) was obtained via the 3-carboxyl derivative of ribavirin 5'-phosphate (2c). Compounds 2a, 2b, and 2d were inactive as inactive as inhibitors of IMP dehydrogenase under conditions where the parent ribavirin 5'-phosphate (2) was an effective inhibitor. Weak inhibitory activity was exhibited by 3 (Ki approximately 200 muM) and 2c (K1 approximately 70 muM). Under conditions where ribavirin (1) is effectively phosphorylated by rat liver nucleoside kinase, the 2'- and 3'-O-methylribavirins (1a and 1b), the 3-carboxylate of ribavirin (1c), and the riboside of 1,2,4-triazole (1d) were totally inactive. The overall results are fully consistent with the lack of antiviral activity of 1a and 1b, while the specificity of ribavirin as an antiviral agent is further underlined by the behavior of the methyl ester 3."}
{"id": "PMID:222910", "title": "Changes in lipid ordering and state of aggregation in lymphocyte plasma membranes after exposure to mitogens.", "content": "An electron spin probe study was made of the effect of a number of mitogenic agents on the ordering and state of aggregation of the plasma membrane lipids of lymphocytes. These agents, which included phytohemagglutinin, Concanavalin A, the calcium ionophore A23187 and periodate, caused a 20% decrease in lipid ordering in the region of the bilayer probed by 5-nitroxide stearic acid. The corresponding methyl ester probe showed marked probe-probe interaction under the same conditions indicating an aggregation of lipids in the area probed by this label. Studies with mixed lipid vesicles and ganglioside-free cells indicate that these areas are rich in glycolipids capable of hydrogen bonding to the ester probe. The decrease in ordering and the increase in aggregation of the membrane lipids were correlated with the patching and capping of the ligand-receptor complexes. Furthermore, the disappearance of fluorescent ligand from the surface of treated cells corresponded with the return of the spectral parameters of the probes to control cell values. It was concluded that glycolipids might play an important role in ligand-induced cell surface changes either as bearers of receptor groups, as in the case of some gangliosides, or in association by hydrogen-bonding with receptor proteins.", "contents": "Changes in lipid ordering and state of aggregation in lymphocyte plasma membranes after exposure to mitogens. An electron spin probe study was made of the effect of a number of mitogenic agents on the ordering and state of aggregation of the plasma membrane lipids of lymphocytes. These agents, which included phytohemagglutinin, Concanavalin A, the calcium ionophore A23187 and periodate, caused a 20% decrease in lipid ordering in the region of the bilayer probed by 5-nitroxide stearic acid. The corresponding methyl ester probe showed marked probe-probe interaction under the same conditions indicating an aggregation of lipids in the area probed by this label. Studies with mixed lipid vesicles and ganglioside-free cells indicate that these areas are rich in glycolipids capable of hydrogen bonding to the ester probe. The decrease in ordering and the increase in aggregation of the membrane lipids were correlated with the patching and capping of the ligand-receptor complexes. Furthermore, the disappearance of fluorescent ligand from the surface of treated cells corresponded with the return of the spectral parameters of the probes to control cell values. It was concluded that glycolipids might play an important role in ligand-induced cell surface changes either as bearers of receptor groups, as in the case of some gangliosides, or in association by hydrogen-bonding with receptor proteins."}
{"id": "PMID:222911", "title": "Isolation of radio-iodinated apical and basal-lateral plasma membranes of toad bladder epithelium.", "content": "The apical and basal-lateral plasma membranes of toad bladder epithelium were radio-iodinated with the glucose-glucose oxidase-lactoperoxidase system. The covalently bound radio iodine was used as a marker during subcellular fractionation and membrane isolation. Homogenization conditions that ensured rupture of more than 80% of the cells without substantial nuclear damage were defined by Normarski optics. The nuclei were separated by differential centrifugation and the apical and basal-lateral components were resolved by differential and sucrose density gradient centrifugation. The apical components yielded two radioactive bands that were identified as glycocalyx and plasma membrane labeled with 125I. The basal-lateral components yielded a hetero-disperse pattern made up of at least 3 radioactive bands, but the bulk of the activity of ouabain-sensitive ATPase comigrated with only one of these bands. The mitochondia, identified by assays for cytochrome oxidase and NADH cytochrome c reductase activities, were separated from the radio-iodine labeled by centrifugation in sucrose density gradients under isokinetic conditions. The labeled glycocalyx and the slowly migrating components of basal-lateral labeling were separated from the radio-iodinated membranes by centrifugation at 100,000 x g x 1 hr after removal of the mitochrondria by the isokinetic method. The labeled membranes were then subjected to ultracentrifugation in sucrose density gradients under isopycnic conditions; the basal-lateral membranes containing ouabain-sensitive ATP-ase were well resolved from the apical membranes by this method. These results provide a relatively rapid method of attaining partial purification of the apical and basal-lateral plasma membranes of toad bladder epithelium.", "contents": "Isolation of radio-iodinated apical and basal-lateral plasma membranes of toad bladder epithelium. The apical and basal-lateral plasma membranes of toad bladder epithelium were radio-iodinated with the glucose-glucose oxidase-lactoperoxidase system. The covalently bound radio iodine was used as a marker during subcellular fractionation and membrane isolation. Homogenization conditions that ensured rupture of more than 80% of the cells without substantial nuclear damage were defined by Normarski optics. The nuclei were separated by differential centrifugation and the apical and basal-lateral components were resolved by differential and sucrose density gradient centrifugation. The apical components yielded two radioactive bands that were identified as glycocalyx and plasma membrane labeled with 125I. The basal-lateral components yielded a hetero-disperse pattern made up of at least 3 radioactive bands, but the bulk of the activity of ouabain-sensitive ATPase comigrated with only one of these bands. The mitochondia, identified by assays for cytochrome oxidase and NADH cytochrome c reductase activities, were separated from the radio-iodine labeled by centrifugation in sucrose density gradients under isokinetic conditions. The labeled glycocalyx and the slowly migrating components of basal-lateral labeling were separated from the radio-iodinated membranes by centrifugation at 100,000 x g x 1 hr after removal of the mitochrondria by the isokinetic method. The labeled membranes were then subjected to ultracentrifugation in sucrose density gradients under isopycnic conditions; the basal-lateral membranes containing ouabain-sensitive ATP-ase were well resolved from the apical membranes by this method. These results provide a relatively rapid method of attaining partial purification of the apical and basal-lateral plasma membranes of toad bladder epithelium."}
{"id": "PMID:222913", "title": "Unusual parapharyngeal lesions.", "content": "Six cases of unusual parapharyngeal lesions are presented in detail along with discussions of the anatomy, pathology, clinical aspects, and treatment methods of lesions in the parapharyngeal space. Newer techniques of CT scanning and selective embolization are discussed as they apply to management of such lesions. A plasmalymphocytic tumor with amyloidosis is described. The authors believe that such a lesion has not been reported previously in the parapharyngeal space.", "contents": "Unusual parapharyngeal lesions. Six cases of unusual parapharyngeal lesions are presented in detail along with discussions of the anatomy, pathology, clinical aspects, and treatment methods of lesions in the parapharyngeal space. Newer techniques of CT scanning and selective embolization are discussed as they apply to management of such lesions. A plasmalymphocytic tumor with amyloidosis is described. The authors believe that such a lesion has not been reported previously in the parapharyngeal space."}
{"id": "PMID:222914", "title": "Chemodectoma in the mid-thyroid region.", "content": "A chemodectoma (non-chromafin paraganglioma), which presented as a neck mass in the mid-thyroid region, is reported in a 36 year old female. Clinically, it resembled a thyroglossal duct cyst and on frozen section it looked like a thyroid adenoma.", "contents": "Chemodectoma in the mid-thyroid region. A chemodectoma (non-chromafin paraganglioma), which presented as a neck mass in the mid-thyroid region, is reported in a 36 year old female. Clinically, it resembled a thyroglossal duct cyst and on frozen section it looked like a thyroid adenoma."}
{"id": "PMID:222915", "title": "Malignant fibrous histiocytoma of the retroperitoneum and genitourinary tract: a clinicopathological correlation and review of the literature.", "content": "Malignant fibrous histiocytoma is an uncommon pleomorphic tumor of the soft tissues possibly arising from the histiocyte. A case of malignant fibrous histiocytoma in the retroperitoneal space is reported. Pathologic and clinical features of this lesion as they relate to the retroperitoneum and genitourinary tract are discussed and suggestions for therapy are presented.", "contents": "Malignant fibrous histiocytoma of the retroperitoneum and genitourinary tract: a clinicopathological correlation and review of the literature. Malignant fibrous histiocytoma is an uncommon pleomorphic tumor of the soft tissues possibly arising from the histiocyte. A case of malignant fibrous histiocytoma in the retroperitoneal space is reported. Pathologic and clinical features of this lesion as they relate to the retroperitoneum and genitourinary tract are discussed and suggestions for therapy are presented."}
{"id": "PMID:222917", "title": "Isolation of a herpesvirus from an American kestrel with inclusion body disease.", "content": "A herpesvirus was isolated from the liver of a captive-bred American kestrel (Falco sparverius) which had died of inclusion body disease. Initial isolation was achieved in chicken embryo fibroblasts after three blind passages. Cell-adapted virus produced a distinct rounding of CEF cells within 24 to 48 h. Biologic and serologic tests suggested that the kestrel virus is similar to falcon herpesvirus and pigeon herpesvirus and is at least partially related to owl herpesvirus. However, serologic tests indicated that the kestrel herpesvirus is neither related to infectious laryngotracheitis virus nor to a herpesvirus from a psittacine bird; (Eupsittula canicularis) with Pacheco's parrot disease. This is the first report on the recovery of a herpesvirus similar to falcon herpesvirus from an American kestrel with naturally-occurring inclusion body disease, and on the serologic comparison between falcon herpesvirus and a psittacine herpesvirus.", "contents": "Isolation of a herpesvirus from an American kestrel with inclusion body disease. A herpesvirus was isolated from the liver of a captive-bred American kestrel (Falco sparverius) which had died of inclusion body disease. Initial isolation was achieved in chicken embryo fibroblasts after three blind passages. Cell-adapted virus produced a distinct rounding of CEF cells within 24 to 48 h. Biologic and serologic tests suggested that the kestrel virus is similar to falcon herpesvirus and pigeon herpesvirus and is at least partially related to owl herpesvirus. However, serologic tests indicated that the kestrel herpesvirus is neither related to infectious laryngotracheitis virus nor to a herpesvirus from a psittacine bird; (Eupsittula canicularis) with Pacheco's parrot disease. This is the first report on the recovery of a herpesvirus similar to falcon herpesvirus from an American kestrel with naturally-occurring inclusion body disease, and on the serologic comparison between falcon herpesvirus and a psittacine herpesvirus."}
{"id": "PMID:222919", "title": "The effect of angiotensin-converting enzyme inhibition on regional blood flow in salt-depleted and salt-loaded normotensive conscious rats.", "content": "The effect of angiotensin-converting enzyme inhibition on regional blood flow was studied in a total of 21 normotensive Wistar rats fed on either low or high salt diet. A new potent angiotensin-converting enzyme inhibitor (CEI), SQ 14,225 was administered intravenously in a dose of 2 mg/Kg to the conscious animals, and changes in fractional distribution of cardiac output were determined with a microsphere method. Prior to administration of CEI, there was no significant difference in mean arterial pressure (MAP) or regional blood flow between salt-depleted and salt-loaded rats. With CEI, MAP did not change significantly in either group. Fractional distribution of cardiac output increased to the kidneys (p less than 0.002), and decreased to the stomach, spleen, and skeletal muscle (p less than 0.02, p less than 0.002, and p less than 0.01, respectively) in the salt-depleted group, while a pattern of blood flow distribution was not changed in the salt-loaded group. These results suggest that angiotensin II plays an important role in regulating regional blood flow in salt-depleted conscious animals, but not in salt-loaded ones.", "contents": "The effect of angiotensin-converting enzyme inhibition on regional blood flow in salt-depleted and salt-loaded normotensive conscious rats. The effect of angiotensin-converting enzyme inhibition on regional blood flow was studied in a total of 21 normotensive Wistar rats fed on either low or high salt diet. A new potent angiotensin-converting enzyme inhibitor (CEI), SQ 14,225 was administered intravenously in a dose of 2 mg/Kg to the conscious animals, and changes in fractional distribution of cardiac output were determined with a microsphere method. Prior to administration of CEI, there was no significant difference in mean arterial pressure (MAP) or regional blood flow between salt-depleted and salt-loaded rats. With CEI, MAP did not change significantly in either group. Fractional distribution of cardiac output increased to the kidneys (p less than 0.002), and decreased to the stomach, spleen, and skeletal muscle (p less than 0.02, p less than 0.002, and p less than 0.01, respectively) in the salt-depleted group, while a pattern of blood flow distribution was not changed in the salt-loaded group. These results suggest that angiotensin II plays an important role in regulating regional blood flow in salt-depleted conscious animals, but not in salt-loaded ones."}
{"id": "PMID:222923", "title": "The beta-adrenergic responses in isolated splenic capsule area of several species of animals.", "content": "In isolated splenic capsules of mouse, rat, guinea pig, rabbit, cat and dog, either a single or a cumulative dose of l- and dl-isoproterenol at a concentration higher than l0(-9) M, induced a relaxation which was inhibited or blocked with pretreatment of 10(-5) M propranolol. At a concentration of 5 x 10(-6) M to 10(-5) M 1- and dl-isoproterenol, an inverse contraction was induced, and such response was prevented or reversed to one of relaxation in the presence of 10(-5) M phentolamine. Application of 10(-5) M epinephrine produced a strong contraction and such was reversed to one of relaxation after addition of 10(-4) M phentolamine. This relaxation was reduced or blocked with pretreatment of 10(-5) M propranolol. Thus, it was confirmed that both alpha- and beta-receptors exist in the splenic capsule area of these different species.", "contents": "The beta-adrenergic responses in isolated splenic capsule area of several species of animals. In isolated splenic capsules of mouse, rat, guinea pig, rabbit, cat and dog, either a single or a cumulative dose of l- and dl-isoproterenol at a concentration higher than l0(-9) M, induced a relaxation which was inhibited or blocked with pretreatment of 10(-5) M propranolol. At a concentration of 5 x 10(-6) M to 10(-5) M 1- and dl-isoproterenol, an inverse contraction was induced, and such response was prevented or reversed to one of relaxation in the presence of 10(-5) M phentolamine. Application of 10(-5) M epinephrine produced a strong contraction and such was reversed to one of relaxation after addition of 10(-4) M phentolamine. This relaxation was reduced or blocked with pretreatment of 10(-5) M propranolol. Thus, it was confirmed that both alpha- and beta-receptors exist in the splenic capsule area of these different species."}
{"id": "PMID:222928", "title": "Tumor-bound immunoglobulin in human gynecologic cancers.", "content": "By the use of immunofluorescence techniques, immunoglobulin of the IgG class was consistently found in touch preparations and in frozen sections of squamous cell carcinomas of the uterine cervix (both keratinizing and nonkeratinizing) and in an adenosquamous cell carcinoma of the cervix, an adenocarcinoma of the cervix, a mixed mesodermal-uterine tumor, and a uterine adenocarcinoma metastasized to the ovaries. Trace amountsof IgM were found in 1 squamous cell carcinoma and in 1 adenocarcinoma of the cervix. Except for 1 tumor specimen consisting primarily of infiltrating lymphocytes that stained positive for human IgG, IgM, IgA, and C3, the tumors were consistently negative for IgA and C3. Specimens made from normal cervical tissue were uniformly negative for all immunoglobulins and complement. Positive staining for human IgG could be eliminated by incubation of the tumor preparations with unconjugated goat antihuman IgG before the preparations were stained with fluorescein isothiocyanate-conjugated goat antihuman IgG. Attempts to elute the tumor-bound IgG with glycine-HCl buffer (pH 2.2) were most successful with the use of unfixed tissue, although the positive staining for IgG could not be entirely eliminated. The elution effects of the low-pH buffer on tissue fixed over 2 hours in 10% Formalin were minimal.", "contents": "Tumor-bound immunoglobulin in human gynecologic cancers. By the use of immunofluorescence techniques, immunoglobulin of the IgG class was consistently found in touch preparations and in frozen sections of squamous cell carcinomas of the uterine cervix (both keratinizing and nonkeratinizing) and in an adenosquamous cell carcinoma of the cervix, an adenocarcinoma of the cervix, a mixed mesodermal-uterine tumor, and a uterine adenocarcinoma metastasized to the ovaries. Trace amountsof IgM were found in 1 squamous cell carcinoma and in 1 adenocarcinoma of the cervix. Except for 1 tumor specimen consisting primarily of infiltrating lymphocytes that stained positive for human IgG, IgM, IgA, and C3, the tumors were consistently negative for IgA and C3. Specimens made from normal cervical tissue were uniformly negative for all immunoglobulins and complement. Positive staining for human IgG could be eliminated by incubation of the tumor preparations with unconjugated goat antihuman IgG before the preparations were stained with fluorescein isothiocyanate-conjugated goat antihuman IgG. Attempts to elute the tumor-bound IgG with glycine-HCl buffer (pH 2.2) were most successful with the use of unfixed tissue, although the positive staining for IgG could not be entirely eliminated. The elution effects of the low-pH buffer on tissue fixed over 2 hours in 10% Formalin were minimal."}
{"id": "PMID:222930", "title": "Role of regional and distant lymph nodes in rejection of feline sarcoma virus-induced tumors in sheep.", "content": "The immune response of regional and distant lymph nodes was compared relative to rejection of feline sarcoma virus (FeSV)-induced tumors in sheep. Following injection of FeSV-transformed allogeneic or autochthonous fibroblasts into the lower leg, small tumors developed at the site of inoculation and subsequently regressed. Efferent lymph from the regional popliteal nodes and distant nodes in the same host was collected for periods up to 40 days after tumor cell inoculation. The cell response in the efferent lymph of the stimulated node was the same regardless of whether inoculum consisted of autochthonous or allogeneic FeSV-transformed sheep cells. There was a rapid rise in total lymphocytes leaving the regional node, beginning at 3 days and peaking at 6--8 days post inoculation. On days 6--8 post inoculation, lymphoblasts appeared in regional lymph ranging from 25 to 40% of the total cell output. The cell population in lymph from distant (nonstimulated) nodes, however, remained morphologically normal throughout the response. Lymphocytes cytotoxic to the injected FeSV-transformed cells appeared in efferent lymph from the regional node within 5 days post inoculation and in lymph from distant nonstimulated nodes several days later. Cytotoxic lymphocytic cells had no \"killing\" effect against the corresponding nontransformed cells if the inoculum was autochthonous in origin; however, they did have such an effect when corresponding nontransformed cells were allogeneic. The cytotoxicity of lymph cells varied according to the type of cells in the lymph. With the use of the growth inhibition assay, it was possible to demonstrate that lymph cell populations high in lymphoblasts \"killed\" all target cells in 24 hours, whereas populations of lymph cells comprised mainly of small lymphocytes took up to 2--3 days to \"kill\" the target cells. Complement-dependent antibody first appeared in lymph from the stimulated popliteal node at 8 days post inoculation and at 12 days post inoculation in blood sera and lymph from distant nodes.", "contents": "Role of regional and distant lymph nodes in rejection of feline sarcoma virus-induced tumors in sheep. The immune response of regional and distant lymph nodes was compared relative to rejection of feline sarcoma virus (FeSV)-induced tumors in sheep. Following injection of FeSV-transformed allogeneic or autochthonous fibroblasts into the lower leg, small tumors developed at the site of inoculation and subsequently regressed. Efferent lymph from the regional popliteal nodes and distant nodes in the same host was collected for periods up to 40 days after tumor cell inoculation. The cell response in the efferent lymph of the stimulated node was the same regardless of whether inoculum consisted of autochthonous or allogeneic FeSV-transformed sheep cells. There was a rapid rise in total lymphocytes leaving the regional node, beginning at 3 days and peaking at 6--8 days post inoculation. On days 6--8 post inoculation, lymphoblasts appeared in regional lymph ranging from 25 to 40% of the total cell output. The cell population in lymph from distant (nonstimulated) nodes, however, remained morphologically normal throughout the response. Lymphocytes cytotoxic to the injected FeSV-transformed cells appeared in efferent lymph from the regional node within 5 days post inoculation and in lymph from distant nonstimulated nodes several days later. Cytotoxic lymphocytic cells had no \"killing\" effect against the corresponding nontransformed cells if the inoculum was autochthonous in origin; however, they did have such an effect when corresponding nontransformed cells were allogeneic. The cytotoxicity of lymph cells varied according to the type of cells in the lymph. With the use of the growth inhibition assay, it was possible to demonstrate that lymph cell populations high in lymphoblasts \"killed\" all target cells in 24 hours, whereas populations of lymph cells comprised mainly of small lymphocytes took up to 2--3 days to \"kill\" the target cells. Complement-dependent antibody first appeared in lymph from the stimulated popliteal node at 8 days post inoculation and at 12 days post inoculation in blood sera and lymph from distant nodes."}
{"id": "PMID:222931", "title": "Reticulum cell neoplasms induced in C57BL/6 mice by cultured virus grown in stromal hematopoietic cell lines.", "content": "Thirty-one adherent cell lines have been established from the spleens, lymph nodes, and bone marrow of C57BL/6 mice carrying radiation leukemia virus (Duplan isolate)-induced reticulum cell neoplasms (RCN). The cell lines had a stable epithelial or fibroblastoid morphology, Supernatant virus from these lines induced splenic and lymph node RCN in 100% of inoculated C57BL/6 mice within 30 days. The disease was generalized and involved many organs. The monolayer cells themselves were not tumor cells and induced RCN through infection of the host with RCN virus. Simultaneous inoculation of in vitro-grown RCN-inducing virus any thymic lymphosarcoma virus induced each disease independently with unaltered incidence, latency period, and organ involvement; no mutual enhancement or inhibition was found, thus two separate mechanisms of action were indicated. Reextraction of the viruses from spleen, lymph nodes, and thymus gland indicated the specific organotropism of each agent. All the adherent cell lines that were derived from hematopoietic tissues produced ample, potent RCN-inducing virus. This high success rate suggests that in the hematopoietic organs the stromal, fibroblastoid cells are a natural habitat for the RCN-inducing virus. The RCN-inducing virus species may well be synthesized in these hematopoietic stromal cells. RCN-inducing virus from culture supernatants contained high-titer infectious ecotropic and xenotropic virus that was titrated. The cultures are being used to clone the RCN-inducing virus and to establish the virologic and molecular properties that endow it with specific RCN-inducing capacity.", "contents": "Reticulum cell neoplasms induced in C57BL/6 mice by cultured virus grown in stromal hematopoietic cell lines. Thirty-one adherent cell lines have been established from the spleens, lymph nodes, and bone marrow of C57BL/6 mice carrying radiation leukemia virus (Duplan isolate)-induced reticulum cell neoplasms (RCN). The cell lines had a stable epithelial or fibroblastoid morphology, Supernatant virus from these lines induced splenic and lymph node RCN in 100% of inoculated C57BL/6 mice within 30 days. The disease was generalized and involved many organs. The monolayer cells themselves were not tumor cells and induced RCN through infection of the host with RCN virus. Simultaneous inoculation of in vitro-grown RCN-inducing virus any thymic lymphosarcoma virus induced each disease independently with unaltered incidence, latency period, and organ involvement; no mutual enhancement or inhibition was found, thus two separate mechanisms of action were indicated. Reextraction of the viruses from spleen, lymph nodes, and thymus gland indicated the specific organotropism of each agent. All the adherent cell lines that were derived from hematopoietic tissues produced ample, potent RCN-inducing virus. This high success rate suggests that in the hematopoietic organs the stromal, fibroblastoid cells are a natural habitat for the RCN-inducing virus. The RCN-inducing virus species may well be synthesized in these hematopoietic stromal cells. RCN-inducing virus from culture supernatants contained high-titer infectious ecotropic and xenotropic virus that was titrated. The cultures are being used to clone the RCN-inducing virus and to establish the virologic and molecular properties that endow it with specific RCN-inducing capacity."}
{"id": "PMID:222932", "title": "[Metabolic shifts in acute period of myocardial infarct and the possibility of their correction with curantil].", "content": "The effect of curantil on the values of energy metabolism in different parts of the myocardium was studied on dogs with experimental myocardial infarction. Tissue respiration, the activity of Krebs' cycle enzymes, cytochrome oxidase, pentose phosphate cycle and glycolysis, and the content of glycogen and adenyl components were studied. It was established that curantil has a positive effect on energy processes, particularly in myocardial areas not involved in ischemia. It is suggested that activation of tissue oxidation enzymes, which improves oxygen utilization and increases ATP production, is among the mechanisms of the curantil effect. It is noted that curantil stimulates the synthesis of glycogen and inhibits its decomposition. The accumulation in the myocardium of AMP, the precursor of adenosine possessing a marked coronarolytic effect, is an important aspect of the drug's action.", "contents": "[Metabolic shifts in acute period of myocardial infarct and the possibility of their correction with curantil]. The effect of curantil on the values of energy metabolism in different parts of the myocardium was studied on dogs with experimental myocardial infarction. Tissue respiration, the activity of Krebs' cycle enzymes, cytochrome oxidase, pentose phosphate cycle and glycolysis, and the content of glycogen and adenyl components were studied. It was established that curantil has a positive effect on energy processes, particularly in myocardial areas not involved in ischemia. It is suggested that activation of tissue oxidation enzymes, which improves oxygen utilization and increases ATP production, is among the mechanisms of the curantil effect. It is noted that curantil stimulates the synthesis of glycogen and inhibits its decomposition. The accumulation in the myocardium of AMP, the precursor of adenosine possessing a marked coronarolytic effect, is an important aspect of the drug's action."}
{"id": "PMID:222934", "title": "Mechanism of renal potassium conservation in the rat.", "content": "The mechanisms responsible for renal potassium (K) conservation during dietary potassium deficiency are poorly understood. This study was undertaken to investigate the time course of potassium conservation as well as the roles of distal sodium (Na) delivery, the distal delivery or sodium plus a nonpermeable anion, mineralocorticoid hormone, renal tissue potassium content, and Na-K-ATPase activity in renal potassium conservation. After 72 hours of a low-potassium diet, basal potassium excretion was negligible. After 24 hours, and even more so after 72 hours of potassium restriction, the kaliuretic response to increasing distal delivery of sodium or sodium plus a nonpermeable anion was impaired. After 24 hours of a low-potassium diet, plasma aldosterone levels fell from 180 +/- 25 to 32 +/- 9 pg/ml (P less than 0.001). Mineralocorticoid hormone given in the first 24 hours of a low-potassium diet resulted in a greater potassium loss (1564 +/- 125 muEq) than it did in controls on the same diet not receiving mineralocorticoid hormone (1032 +/- 83 muEq, P less than 0.005). In contrast, after 72 hours of diet, large doses of mineralocorticoid hormone failed to cause a kaliuresis in either anesthetized or conscious rats. After both 24 and 72 hours, outer medullary Na-K-ATPase was increased. At 72 hours, cortical, medullary, and papillary tissue potassium concentrations were significantly depressed. Acute administration of potassium repleted tissue potassium levels and restored basal and saline-stimulated potassium excretion to normal. Although potassium excretion was markedly depressed after 24 hours of the low-potassium diet, 42K microinjection studies of the distal nephron did not suggest any increase in potassium reabsorption. Following 72 hours of diet, potassium reabsorption increased significantly from 26 +/- 2% to 41 +/- 2% (P less than 0.001). We conclude that renal potassium conservation is at first primarily related to a decrease in potassium secretion, which is most likely mediated by falling levels of mineralocorticoid hormone. After 72 hours of the potassium-deficient diet, however, potassium conservation becomes independent of mineralocorticoid hormone, distal delivery of sodium, and Na-K-ATPase. The decreased tissue potassium content appears to be the primary mediator of both the increase in potassium reabsorption by the distal nephron and of renal potassium conservation at this time.", "contents": "Mechanism of renal potassium conservation in the rat. The mechanisms responsible for renal potassium (K) conservation during dietary potassium deficiency are poorly understood. This study was undertaken to investigate the time course of potassium conservation as well as the roles of distal sodium (Na) delivery, the distal delivery or sodium plus a nonpermeable anion, mineralocorticoid hormone, renal tissue potassium content, and Na-K-ATPase activity in renal potassium conservation. After 72 hours of a low-potassium diet, basal potassium excretion was negligible. After 24 hours, and even more so after 72 hours of potassium restriction, the kaliuretic response to increasing distal delivery of sodium or sodium plus a nonpermeable anion was impaired. After 24 hours of a low-potassium diet, plasma aldosterone levels fell from 180 +/- 25 to 32 +/- 9 pg/ml (P less than 0.001). Mineralocorticoid hormone given in the first 24 hours of a low-potassium diet resulted in a greater potassium loss (1564 +/- 125 muEq) than it did in controls on the same diet not receiving mineralocorticoid hormone (1032 +/- 83 muEq, P less than 0.005). In contrast, after 72 hours of diet, large doses of mineralocorticoid hormone failed to cause a kaliuresis in either anesthetized or conscious rats. After both 24 and 72 hours, outer medullary Na-K-ATPase was increased. At 72 hours, cortical, medullary, and papillary tissue potassium concentrations were significantly depressed. Acute administration of potassium repleted tissue potassium levels and restored basal and saline-stimulated potassium excretion to normal. Although potassium excretion was markedly depressed after 24 hours of the low-potassium diet, 42K microinjection studies of the distal nephron did not suggest any increase in potassium reabsorption. Following 72 hours of diet, potassium reabsorption increased significantly from 26 +/- 2% to 41 +/- 2% (P less than 0.001). We conclude that renal potassium conservation is at first primarily related to a decrease in potassium secretion, which is most likely mediated by falling levels of mineralocorticoid hormone. After 72 hours of the potassium-deficient diet, however, potassium conservation becomes independent of mineralocorticoid hormone, distal delivery of sodium, and Na-K-ATPase. The decreased tissue potassium content appears to be the primary mediator of both the increase in potassium reabsorption by the distal nephron and of renal potassium conservation at this time."}
{"id": "PMID:222935", "title": "Quantitative indices of clinical uremia.", "content": "The disabling, dialysis-responsive symptoms of clinical uremia primarily represent impaired functions of the nervous system. Accordingly, these studies used several quantitative electrophysiologic and cognition-dependent probes of nervous system function: peripheral nerve-conduction velocity, response latency and amplitude; electroencephalographic (EEG) power-spectrum analysis; visual evoked response latency; EEG responses to photic driving; and measures of integrated behavioral performance that stressed sustained and selective attention, reaction time, speed of decision-making, short-term memory, and mental manipulation of symbols. Probes of quanitified central nervous system function consistently revealed impairments that varied directly with the degree of renal failure, that improved following onset of maintenance dialysis, and that improved still further after successful renal transplantation. In contrast, measures of peripheral nerve function were generally unchanged. Neurobehavioral measures that are relevant to uremic symptomatology provide quantitative estimates of the clinically significant, whole-organism biologic effects of renal failure and its several treatments. Applications of such measures in studies of symptomatic states other than uremia are indicated also.", "contents": "Quantitative indices of clinical uremia. The disabling, dialysis-responsive symptoms of clinical uremia primarily represent impaired functions of the nervous system. Accordingly, these studies used several quantitative electrophysiologic and cognition-dependent probes of nervous system function: peripheral nerve-conduction velocity, response latency and amplitude; electroencephalographic (EEG) power-spectrum analysis; visual evoked response latency; EEG responses to photic driving; and measures of integrated behavioral performance that stressed sustained and selective attention, reaction time, speed of decision-making, short-term memory, and mental manipulation of symbols. Probes of quanitified central nervous system function consistently revealed impairments that varied directly with the degree of renal failure, that improved following onset of maintenance dialysis, and that improved still further after successful renal transplantation. In contrast, measures of peripheral nerve function were generally unchanged. Neurobehavioral measures that are relevant to uremic symptomatology provide quantitative estimates of the clinically significant, whole-organism biologic effects of renal failure and its several treatments. Applications of such measures in studies of symptomatic states other than uremia are indicated also."}
{"id": "PMID:222937", "title": "[Butterfly-shaped dystrophy of the macula with absent pre-beta-fraction of the electropherogram of the serum lipoproteins (author's transl)].", "content": "A case of butterfly-shaped dystrophy of the macula is described. Clinical and electrophysiological data are compared with those of 11 cases described in the literature. An aberrant electropherogram of the lipoproteins examined at two different laboratories was found to be present. The serum lipoproteins showed total lack of the pre-beta-fraction. Two children of the patient were examined, too. They showed minimal macular changes which however did not justify the diagnosis of butterfly-shaped dystrophy. Their pre-beta-lipoprotein fractions of the electropherogram were below the Finish standards. The proband is the first case of butterfly-shaped macular dystrophy described from Finland and therefore it was not possible to control the laboratory findings on other cases. The absence of the pre-beta-lipoprotein fraction might be an important feature of butterfly-shaped dystrophy of the macula.", "contents": "[Butterfly-shaped dystrophy of the macula with absent pre-beta-fraction of the electropherogram of the serum lipoproteins (author's transl)]. A case of butterfly-shaped dystrophy of the macula is described. Clinical and electrophysiological data are compared with those of 11 cases described in the literature. An aberrant electropherogram of the lipoproteins examined at two different laboratories was found to be present. The serum lipoproteins showed total lack of the pre-beta-fraction. Two children of the patient were examined, too. They showed minimal macular changes which however did not justify the diagnosis of butterfly-shaped dystrophy. Their pre-beta-lipoprotein fractions of the electropherogram were below the Finish standards. The proband is the first case of butterfly-shaped macular dystrophy described from Finland and therefore it was not possible to control the laboratory findings on other cases. The absence of the pre-beta-lipoprotein fraction might be an important feature of butterfly-shaped dystrophy of the macula."}
{"id": "PMID:222938", "title": "[A new oculo-dento-cutaneous syndrome (author's transl)].", "content": "A report is given about an 11-year-old girl with multiple anomalies - specially concerning the eye, followed by a comparison with other similar syndromes as presented in literature.", "contents": "[A new oculo-dento-cutaneous syndrome (author's transl)]. A report is given about an 11-year-old girl with multiple anomalies - specially concerning the eye, followed by a comparison with other similar syndromes as presented in literature."}
{"id": "PMID:222939", "title": "[Virusenteritis in childhood (author's transl)].", "content": "About 20% of infantile enteritis are caused by bacterial infections. The most cases of non bacterial infantile enteritis are supposed to be viral infections. Arguments for the existence of enterotropic viruses arised the first time in 1943. Since the middle of the fifties, various kinds of enteroviruses are known to be causative agents of infantile gastroenteritis. The same is true occasionally for some types of adenovirus. In 1973 the Norwalk-agent was discovered provocing enteritis mainly in adults. The most important progress was achieved by the discovery of Rotavirus. The viruses of this group nowadays are ment to be the most wide spread causes of enteritis in human beings and many mammalians. Rotavirus can be found in about 40--60% of acute infantile gastroenteritis in many parts of the world. Furthermore, in the last years of Coronavirus and Astrovirus were detected as causative agents of gastroenteritis in some domestic animals and probably in human beings too.", "contents": "[Virusenteritis in childhood (author's transl)]. About 20% of infantile enteritis are caused by bacterial infections. The most cases of non bacterial infantile enteritis are supposed to be viral infections. Arguments for the existence of enterotropic viruses arised the first time in 1943. Since the middle of the fifties, various kinds of enteroviruses are known to be causative agents of infantile gastroenteritis. The same is true occasionally for some types of adenovirus. In 1973 the Norwalk-agent was discovered provocing enteritis mainly in adults. The most important progress was achieved by the discovery of Rotavirus. The viruses of this group nowadays are ment to be the most wide spread causes of enteritis in human beings and many mammalians. Rotavirus can be found in about 40--60% of acute infantile gastroenteritis in many parts of the world. Furthermore, in the last years of Coronavirus and Astrovirus were detected as causative agents of gastroenteritis in some domestic animals and probably in human beings too."}
{"id": "PMID:222940", "title": "[Visceral leishmaniasis (Kala-Azar) in a 3-year-old German infant (author's transl)].", "content": "The article reports on a case of visceral leishmaniasis in a 3-year-old child of German residents in Rome who had passed two vacations on the isle of Ischia. Initial signs were intermittent temperatures, marked anorexia, hepatosplenomegaly and pancytopenia, with spontaneous recovery after three weeks. At that time, leishmania serology was already positive, whereas no leishmania were found in several bone marrow preparations despite a most thorough search. During the following eight weeks, the patient had chickenpox and mumps. During the mumps, relapse of the visceral leishmaniasis occurred, associated with a dramatic increase of the hepatosplenomegaly and recurring pancytopenia. It was only now that we could discover multiple leishmania infection of the bone marrow. Subsequent therapy with sodium stibogluconate (Pentostam) was effective without any complications, and eventually cured the patient.", "contents": "[Visceral leishmaniasis (Kala-Azar) in a 3-year-old German infant (author's transl)]. The article reports on a case of visceral leishmaniasis in a 3-year-old child of German residents in Rome who had passed two vacations on the isle of Ischia. Initial signs were intermittent temperatures, marked anorexia, hepatosplenomegaly and pancytopenia, with spontaneous recovery after three weeks. At that time, leishmania serology was already positive, whereas no leishmania were found in several bone marrow preparations despite a most thorough search. During the following eight weeks, the patient had chickenpox and mumps. During the mumps, relapse of the visceral leishmaniasis occurred, associated with a dramatic increase of the hepatosplenomegaly and recurring pancytopenia. It was only now that we could discover multiple leishmania infection of the bone marrow. Subsequent therapy with sodium stibogluconate (Pentostam) was effective without any complications, and eventually cured the patient."}
{"id": "PMID:222941", "title": "Spontaneous rupture of the Achilles tendon - a sign of hyperlipoproteinaemia (HLP) type II.", "content": "In biopsies from spontaneously ruptured Achilles tendons a serum lipid and lipoprotein analysis was performed in fifty nine patients. In nine males considerable histological signs of lipid deposition were detectable. The tendon fibers were found to be partly desintegrated. Only in these cases LDL-cholesterol values were found to exceed the normal range indicative of type II hyperlipoproteinaemia (HLP). None of the fifty remaining patients presented biochemical or clinical signs of disorders of lipid metabolism. The observations demonstrate that a spontaneous rupture of Achilles tendom may indicate a primary type II HLP.", "contents": "Spontaneous rupture of the Achilles tendon - a sign of hyperlipoproteinaemia (HLP) type II. In biopsies from spontaneously ruptured Achilles tendons a serum lipid and lipoprotein analysis was performed in fifty nine patients. In nine males considerable histological signs of lipid deposition were detectable. The tendon fibers were found to be partly desintegrated. Only in these cases LDL-cholesterol values were found to exceed the normal range indicative of type II hyperlipoproteinaemia (HLP). None of the fifty remaining patients presented biochemical or clinical signs of disorders of lipid metabolism. The observations demonstrate that a spontaneous rupture of Achilles tendom may indicate a primary type II HLP."}
{"id": "PMID:222943", "title": "[Effect of short-term antiorthostatic hypokinesia on carbohydrate metabolic indices and on the beta-lipoprotein content in human blood].", "content": "Before and after 5-day bed rest in the head-down position (at an angle of --4.5 degrees) the healthy male test subjects were exposed to selective catheterization with blood samples withdrawn drom different compartments of the cardiovascular system. The content of glucose insulin lactic acid and beta-lipoproteins was measured. After bed rest the systemic circulation--mixed arterial and venous blood--showed a trend for a decrease of carbohydrate metabolism and an increase of the content of beta-lipoproteins. Transcapillary metabolism in different organs, first of all, in the brain and liver altered significantly. The liver began to release glucose and ceased to utilize lactic acid whereas the brain increased substantially its release of beta-lipoproteins. The data obtained were analyzed using a model of carbohydrate metabolism to control and artifical pancreas.", "contents": "[Effect of short-term antiorthostatic hypokinesia on carbohydrate metabolic indices and on the beta-lipoprotein content in human blood]. Before and after 5-day bed rest in the head-down position (at an angle of --4.5 degrees) the healthy male test subjects were exposed to selective catheterization with blood samples withdrawn drom different compartments of the cardiovascular system. The content of glucose insulin lactic acid and beta-lipoproteins was measured. After bed rest the systemic circulation--mixed arterial and venous blood--showed a trend for a decrease of carbohydrate metabolism and an increase of the content of beta-lipoproteins. Transcapillary metabolism in different organs, first of all, in the brain and liver altered significantly. The liver began to release glucose and ceased to utilize lactic acid whereas the brain increased substantially its release of beta-lipoproteins. The data obtained were analyzed using a model of carbohydrate metabolism to control and artifical pancreas."}
{"id": "PMID:222958", "title": "Vasoactive intestinal peptide and its relationship to ganglion cell differentiation in neuroblastic tumors.", "content": "Immunohistochemical studies have demonstrated that immunoreactive vasoactive intestinal peptide is present in, and restricted to, the differentiating and mature ganglion cells in a variety of normal and neoplastic neural tissues. In a composite pheochromocytoma-ganglioneuroma (associated with the syndrome of watery diarrhea, hypokalemia, and hypochlorhydria), five ganglioneuroblastomas, five ganglioneuromas (two of which were associated with diarrheal syndromes), an unusual mixed neuroblastoma-ganglioneuroma, and four normal sympathetic ganglia, vasoactive intestinal peptide was present in differentiating and mature ganglion cells. The peptide was also demonstrated in isolated ganglion cells in two pheochromocytomas but was not present in pheochromocytes, Schwann cells, or undifferentiated neuroblastic cells in the neuroblastomas and ganglioneuroblastomas. These studies indicate that the presence and presumably the production of vasoactive intestinal peptide thus reflect a particular line of neuroblastic differentiation and are not merely a reflection of common derivation of these tissues. Our identification of vasoactive intestinal peptide in neurogenic tumors associated with diarrhea supports the contention that the peptide might be an important diarrheogenic factor in these tumors.", "contents": "Vasoactive intestinal peptide and its relationship to ganglion cell differentiation in neuroblastic tumors. Immunohistochemical studies have demonstrated that immunoreactive vasoactive intestinal peptide is present in, and restricted to, the differentiating and mature ganglion cells in a variety of normal and neoplastic neural tissues. In a composite pheochromocytoma-ganglioneuroma (associated with the syndrome of watery diarrhea, hypokalemia, and hypochlorhydria), five ganglioneuroblastomas, five ganglioneuromas (two of which were associated with diarrheal syndromes), an unusual mixed neuroblastoma-ganglioneuroma, and four normal sympathetic ganglia, vasoactive intestinal peptide was present in differentiating and mature ganglion cells. The peptide was also demonstrated in isolated ganglion cells in two pheochromocytomas but was not present in pheochromocytes, Schwann cells, or undifferentiated neuroblastic cells in the neuroblastomas and ganglioneuroblastomas. These studies indicate that the presence and presumably the production of vasoactive intestinal peptide thus reflect a particular line of neuroblastic differentiation and are not merely a reflection of common derivation of these tissues. Our identification of vasoactive intestinal peptide in neurogenic tumors associated with diarrhea supports the contention that the peptide might be an important diarrheogenic factor in these tumors."}
{"id": "PMID:222963", "title": "Growth factors and gangliosides: a possible new perspective in neuronal growth control.", "content": "For many permanent cell lines the transition from a growing (P) to a resting (R) state is reversibly controlled by growth factors present in serum. This P-to-R transition was studied in a neuronal cell line (B104) with respect to the action of serum, dibutyryl cyclic AMP (DBcAMP), gangliosides, and a glioma cell-produced growth factor GGF. In this cell system gangliosides seem to act as differentiation and survival factors. The kinetics of uptake of radioactively labeled gangliosides and survival experiments both support the idea of the stable incorporation of exogenously added gangliosides into the cells. Based on the experimental evidence a new model of cell development is proposed. Thus in addition to the R or Go state, which in this cell system is rather unstable and probably regulated by cyclic nucleotides, we postulate a differentiated D state, which is controlled by gangliosides and which is characterized by its stability (survival time). This D compartment seems to be closer to the in vivo differentiated neuron than does the R or P state. tthe possible mechanisms for the action of gangliosides are discussed.", "contents": "Growth factors and gangliosides: a possible new perspective in neuronal growth control. For many permanent cell lines the transition from a growing (P) to a resting (R) state is reversibly controlled by growth factors present in serum. This P-to-R transition was studied in a neuronal cell line (B104) with respect to the action of serum, dibutyryl cyclic AMP (DBcAMP), gangliosides, and a glioma cell-produced growth factor GGF. In this cell system gangliosides seem to act as differentiation and survival factors. The kinetics of uptake of radioactively labeled gangliosides and survival experiments both support the idea of the stable incorporation of exogenously added gangliosides into the cells. Based on the experimental evidence a new model of cell development is proposed. Thus in addition to the R or Go state, which in this cell system is rather unstable and probably regulated by cyclic nucleotides, we postulate a differentiated D state, which is controlled by gangliosides and which is characterized by its stability (survival time). This D compartment seems to be closer to the in vivo differentiated neuron than does the R or P state. tthe possible mechanisms for the action of gangliosides are discussed."}
{"id": "PMID:222964", "title": "Activation of cyclic AMP-dependent protein kinase and stimulation of protein phosphorylation in response to adenosine in C-1300 murine neuroblastoma.", "content": "DEAE-cellulose chromatography of the 20,000g supernatant fraction of homogenates of C-1300 murine neuroblastoma (clone N2a) yields one major and two minor peaks of cyclic AMP-dependent protein kinase activity. Assessment of the endogenous activation state of the enzyme(s) reveals that the enzyme is fully activated by the treatment of whole cells with adenosine (10 microM) in the presence of the phosphodiesterase inhibitor Ro 20 1724 (0.7 mM). This treatment produces a large elevation in the cyclic AMP content of the cells. The treatment of whole cells with adenosine alone (1-100 microM) or Ro 20 1724 alone (0.1-0.7 mM) produces minimal elevations in cyclic AMP but nevertheless causes significant activations of cyclic AMP-dependent protein kinase. The autophosphorylation of whole homogenates of treated and untreated cells was studied using [gamma-32P] ATP, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Treatments which activate cyclic AMP-dependent protein kinase selectively stimulate the incorporation of 32P into several proteins. This stimulation is most prominent in the 15,000-dalton protein band. The addition of cyclic AMP to phosphorylation reactions containing homogenate of untreated cells stimulates the phosphorylation of the same protein bands. These results indicate that adenosine may have regulatory functions through its effect on the cyclic AMP:cyclic AMP-dependent protein kinase system.", "contents": "Activation of cyclic AMP-dependent protein kinase and stimulation of protein phosphorylation in response to adenosine in C-1300 murine neuroblastoma. DEAE-cellulose chromatography of the 20,000g supernatant fraction of homogenates of C-1300 murine neuroblastoma (clone N2a) yields one major and two minor peaks of cyclic AMP-dependent protein kinase activity. Assessment of the endogenous activation state of the enzyme(s) reveals that the enzyme is fully activated by the treatment of whole cells with adenosine (10 microM) in the presence of the phosphodiesterase inhibitor Ro 20 1724 (0.7 mM). This treatment produces a large elevation in the cyclic AMP content of the cells. The treatment of whole cells with adenosine alone (1-100 microM) or Ro 20 1724 alone (0.1-0.7 mM) produces minimal elevations in cyclic AMP but nevertheless causes significant activations of cyclic AMP-dependent protein kinase. The autophosphorylation of whole homogenates of treated and untreated cells was studied using [gamma-32P] ATP, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Treatments which activate cyclic AMP-dependent protein kinase selectively stimulate the incorporation of 32P into several proteins. This stimulation is most prominent in the 15,000-dalton protein band. The addition of cyclic AMP to phosphorylation reactions containing homogenate of untreated cells stimulates the phosphorylation of the same protein bands. These results indicate that adenosine may have regulatory functions through its effect on the cyclic AMP:cyclic AMP-dependent protein kinase system."}
{"id": "PMID:222965", "title": "Cholera toxin-catalysed ADP-ribosylation of erythrocyte proteins: general properties.", "content": "Upon incubation of lysed pigeon erythrocytes with NAD, adenosine diphosphate-ribose (ADP-ribose) is incorporated into nuclear poly ADP-ribose and into an unidentified acid-insoluble product of the cytosol. The properties of these incorporations have been examined and a method developed for reducing their amount whilst retaining the sensitivity of the lysate to cholera toxin. This method has allowed the detection and description of a set of cholera toxin-specific ADP-ribose transfers to membrane-bound and soluble proteins under conditions that lead to adenylate cyclase activation.", "contents": "Cholera toxin-catalysed ADP-ribosylation of erythrocyte proteins: general properties. Upon incubation of lysed pigeon erythrocytes with NAD, adenosine diphosphate-ribose (ADP-ribose) is incorporated into nuclear poly ADP-ribose and into an unidentified acid-insoluble product of the cytosol. The properties of these incorporations have been examined and a method developed for reducing their amount whilst retaining the sensitivity of the lysate to cholera toxin. This method has allowed the detection and description of a set of cholera toxin-specific ADP-ribose transfers to membrane-bound and soluble proteins under conditions that lead to adenylate cyclase activation."}
{"id": "PMID:222966", "title": "Effect of metabolic inhibitors on vasopressin-stimulated transport systems in the toad bladder.", "content": "Vasopressin increases the permeability of receptor cells to water and, in tissues such as toad bladder, to solutes such as urea. While cyclic AMP appears to play a major role in mediating the effects of vasopressin, there is evidence that activation of the water permeability system and the urea permeability system involves separate pathways. In the present study, we have shown that inhibitors of oxidative metabolism (rotenone, dinitrophenol, and methylene blue) selectively inhibit either vasopressin-stimulated water flow or vasopressin-stimulated urea transport. There was no inhibition, however, when exogenous cyclic AMP was substituted for vasopressin, and little to no inhibition when the potent analogue 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP) was employed. Rotenone had no effect on adenylate cyclase activity or cyclic AMP levels within the cell; dinitrophenol decreased adenylate cyclase activity minimally. Additional studies with vinblastine and nocodazole, inhibitors of microtubule assembly, demonstrated an inhibition of vasopressin and cyclic AMP-stimulated water flow but showed no effect on urea transport. We would conclude that water and urea transport, as examples of hormone-stimulated processes, have different links to cell metabolism, and that in addition to cyclic AMP, a non-nucleotide pathway may be involved in the action of vasopressin.", "contents": "Effect of metabolic inhibitors on vasopressin-stimulated transport systems in the toad bladder. Vasopressin increases the permeability of receptor cells to water and, in tissues such as toad bladder, to solutes such as urea. While cyclic AMP appears to play a major role in mediating the effects of vasopressin, there is evidence that activation of the water permeability system and the urea permeability system involves separate pathways. In the present study, we have shown that inhibitors of oxidative metabolism (rotenone, dinitrophenol, and methylene blue) selectively inhibit either vasopressin-stimulated water flow or vasopressin-stimulated urea transport. There was no inhibition, however, when exogenous cyclic AMP was substituted for vasopressin, and little to no inhibition when the potent analogue 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP) was employed. Rotenone had no effect on adenylate cyclase activity or cyclic AMP levels within the cell; dinitrophenol decreased adenylate cyclase activity minimally. Additional studies with vinblastine and nocodazole, inhibitors of microtubule assembly, demonstrated an inhibition of vasopressin and cyclic AMP-stimulated water flow but showed no effect on urea transport. We would conclude that water and urea transport, as examples of hormone-stimulated processes, have different links to cell metabolism, and that in addition to cyclic AMP, a non-nucleotide pathway may be involved in the action of vasopressin."}
{"id": "PMID:222967", "title": "Predictive value of the analogy between hormone-sensitive adenylate cyclase and light-sensitive photoreceptor cyclic GMP phosphodiesterase: a specific role for a light-sensitive GTPase  as a component in the activation sequence.", "content": "We report experiments which involve a light sensitive GTPase in the light dependent activation of retinal rod 3'5'-cyclic guanosine monophosphate (cGMP) phosphodiesterase (PDE). The data suggest that the light activated GTPase is intermediate between rhodopsin and PDE in the light-dependent activation sequence. We list the many striking similarities between hormone sensitive adenylate cyclase and light activated PDE in order to emphasize that the findings presented herein may have predictive value for ongoing studies of the hormone sensitive adenylate cyclase specifically regarding the role of the hormone activated GTPase in the activation sequence.", "contents": "Predictive value of the analogy between hormone-sensitive adenylate cyclase and light-sensitive photoreceptor cyclic GMP phosphodiesterase: a specific role for a light-sensitive GTPase  as a component in the activation sequence. We report experiments which involve a light sensitive GTPase in the light dependent activation of retinal rod 3'5'-cyclic guanosine monophosphate (cGMP) phosphodiesterase (PDE). The data suggest that the light activated GTPase is intermediate between rhodopsin and PDE in the light-dependent activation sequence. We list the many striking similarities between hormone sensitive adenylate cyclase and light activated PDE in order to emphasize that the findings presented herein may have predictive value for ongoing studies of the hormone sensitive adenylate cyclase specifically regarding the role of the hormone activated GTPase in the activation sequence."}
{"id": "PMID:222968", "title": "Interaction between glycophorin and phospholipids in recombined systems.", "content": "Both the MN-glycoprotein from human erythrocytes and the hydrophobic fragment from the protein isolated with trypsin treatment, T(is), have been recombined with egg phosphatidylcholine in bilayers at various phospholipid/protein ratios. In order to investigate the effect of the protein on the phospholipid headgroups, 31P nuclear magnetic resonance spectra were obtained with the MN-glycoprotein recombined with egg phosphatidylcholine, which revealed two classes of phospholipid environments, one immobilized and one not immobilized. Electron spin resonance (ESR) of fatty acid methyl ester spin labels provided supporting evidence. Computer analysis of the ESR spectra indicate that 4-5 moles of phospholipid are immobilized per mole of protein over a wide range of lipid-to-protein ratios. The immobilization of the phospholipids appears mediated by both the polar headgroups and the hydrocarbon tails of the phospholipid.", "contents": "Interaction between glycophorin and phospholipids in recombined systems. Both the MN-glycoprotein from human erythrocytes and the hydrophobic fragment from the protein isolated with trypsin treatment, T(is), have been recombined with egg phosphatidylcholine in bilayers at various phospholipid/protein ratios. In order to investigate the effect of the protein on the phospholipid headgroups, 31P nuclear magnetic resonance spectra were obtained with the MN-glycoprotein recombined with egg phosphatidylcholine, which revealed two classes of phospholipid environments, one immobilized and one not immobilized. Electron spin resonance (ESR) of fatty acid methyl ester spin labels provided supporting evidence. Computer analysis of the ESR spectra indicate that 4-5 moles of phospholipid are immobilized per mole of protein over a wide range of lipid-to-protein ratios. The immobilization of the phospholipids appears mediated by both the polar headgroups and the hydrocarbon tails of the phospholipid."}
{"id": "PMID:222969", "title": "Erythrocyte spectrin alteration induced by low-density lipoprotein.", "content": "Addition of human plasma low-density lipoproteins (LDL) to intact human erythrocytes induces the erythrocytes to undergo morphologic transition from biconcave disks to echinocytes and spherocytes. The transformation is time-dependent. Two hours are required before echinocytes are detected by scanning electron microscopy. After two hours, LDL also decrease the phosphate content of spectrin by 40% relative to the control, suggesting that these lipoproteins modulate cell shape by influencing phosphorylation-dephosphorylation of a membrane-associated cytoskeletal protein. LDL do not induce depletion of intracellular adenosine triphosphate (ATP), nor do they inhibit cyclic adenosine monophosphate-independent protein kinases which phosphorylate spectrin. LDL stimulate membrane-bound phosphatases by a factor of two, thereby reducing the amount of phosphate covalently bound to membrane proteins. The observed effects are specific for LDL. High-density lipoproteins (HDL) do not stimulate dephosphorylation of spectrin or alter erythrocyte morphology. However, HDL protect the erythrocytes against LDL-induced alterations. These data suggest that the circulating lipoproteins have a role in maintaining erythrocyte morphology by regulating the extent of phosphorylation of spectrin.", "contents": "Erythrocyte spectrin alteration induced by low-density lipoprotein. Addition of human plasma low-density lipoproteins (LDL) to intact human erythrocytes induces the erythrocytes to undergo morphologic transition from biconcave disks to echinocytes and spherocytes. The transformation is time-dependent. Two hours are required before echinocytes are detected by scanning electron microscopy. After two hours, LDL also decrease the phosphate content of spectrin by 40% relative to the control, suggesting that these lipoproteins modulate cell shape by influencing phosphorylation-dephosphorylation of a membrane-associated cytoskeletal protein. LDL do not induce depletion of intracellular adenosine triphosphate (ATP), nor do they inhibit cyclic adenosine monophosphate-independent protein kinases which phosphorylate spectrin. LDL stimulate membrane-bound phosphatases by a factor of two, thereby reducing the amount of phosphate covalently bound to membrane proteins. The observed effects are specific for LDL. High-density lipoproteins (HDL) do not stimulate dephosphorylation of spectrin or alter erythrocyte morphology. However, HDL protect the erythrocytes against LDL-induced alterations. These data suggest that the circulating lipoproteins have a role in maintaining erythrocyte morphology by regulating the extent of phosphorylation of spectrin."}
{"id": "PMID:222970", "title": "Cancer of the breast. Gross and histologic pathlogy.", "content": "Increased demands are made upon the pathologist to work closely with the surgeon and the mammographer in the interest of early detection. The smallest of cancers and the very earliest phases of neoplastic development are being detected, necessitating fine discriminations between cancer and noncancer. Agreement is not always uniform at these new frontiers of diagnosis, and accuracy is paramount. Tumors are populations of heterogeneous cells. Their morphology lends itself poorly to simple categorization, and their biology is not always accurately reflected in their gross and histologic appearances. Clearly evident to the pathologist are the limitations of morphology, of the light microscope and of routine techniques for examining surgical specimens. Paradoxically, \"noninvasive\" cancers occasionally metastasize, and lymph nodes originally \"free\" of cancer are found to contain metastases on more meticulous re-examination. Notwithstanding these limitations a prognostic statement can be made with relative confidence with regard to certain morphologic types of carcinoma. Pure intraductal carcinoma and lobular carcinoma in situ entail negligible threat to normal life expectancy if the breast is thoroughly removed. Other types with a favorable prognosis are intracystic papillary carcinomas and pure mucinous carcinomas. Tumors classified as well differentiated or tubular adenocarcinoma infrequently metastasize and have excellent prospects for cure. Unfortunately, these and other favorable histologic types comprise less than one quarter of all mammary carcinomas. Most carcinomas are without such distinctive features. In this category the degree of anaplasia and the nature of the tumor borders, as well as the presence or absence of blood vessel invasion, dermal lymphatic invasion and metastases in regional lymph nodes, are of major importance in arriving at an estimate of prognosis.", "contents": "Cancer of the breast. Gross and histologic pathlogy. Increased demands are made upon the pathologist to work closely with the surgeon and the mammographer in the interest of early detection. The smallest of cancers and the very earliest phases of neoplastic development are being detected, necessitating fine discriminations between cancer and noncancer. Agreement is not always uniform at these new frontiers of diagnosis, and accuracy is paramount. Tumors are populations of heterogeneous cells. Their morphology lends itself poorly to simple categorization, and their biology is not always accurately reflected in their gross and histologic appearances. Clearly evident to the pathologist are the limitations of morphology, of the light microscope and of routine techniques for examining surgical specimens. Paradoxically, \"noninvasive\" cancers occasionally metastasize, and lymph nodes originally \"free\" of cancer are found to contain metastases on more meticulous re-examination. Notwithstanding these limitations a prognostic statement can be made with relative confidence with regard to certain morphologic types of carcinoma. Pure intraductal carcinoma and lobular carcinoma in situ entail negligible threat to normal life expectancy if the breast is thoroughly removed. Other types with a favorable prognosis are intracystic papillary carcinomas and pure mucinous carcinomas. Tumors classified as well differentiated or tubular adenocarcinoma infrequently metastasize and have excellent prospects for cure. Unfortunately, these and other favorable histologic types comprise less than one quarter of all mammary carcinomas. Most carcinomas are without such distinctive features. In this category the degree of anaplasia and the nature of the tumor borders, as well as the presence or absence of blood vessel invasion, dermal lymphatic invasion and metastases in regional lymph nodes, are of major importance in arriving at an estimate of prognosis."}
{"id": "PMID:222974", "title": "Developmental aspect of phenylalanine hydroxylase in the rat -- hormonal influences.", "content": "Interpretations of the development of phenylalanine hydroxylase (PAH) in rat liver have been controversial, and the mechanism of ontogenic changes have not yet been elucidated. Fetal PAH activity at a gestational age of 21 days appeared to reach 32% that of adult male level at birth. The in vivo effectiveness of fetal PAH activity was correlated with enhancement of blood tyrosine, while amino-transferase activity appeared only after birth. No sex difference was noted in weaning rats, whereas, in adult females, PAH activity was only 42% that of males. Investigating hormonal influences on liver PAH activity we noted no change of enzyme activity following hydrocortisone, ACTH and estradiol treatment. However, 4 days of testosterone treatment in weaning female rats increased PAH activity (X1.7). Therefore, testosterone could explain increased PAH activity in adult males.", "contents": "Developmental aspect of phenylalanine hydroxylase in the rat -- hormonal influences. Interpretations of the development of phenylalanine hydroxylase (PAH) in rat liver have been controversial, and the mechanism of ontogenic changes have not yet been elucidated. Fetal PAH activity at a gestational age of 21 days appeared to reach 32% that of adult male level at birth. The in vivo effectiveness of fetal PAH activity was correlated with enhancement of blood tyrosine, while amino-transferase activity appeared only after birth. No sex difference was noted in weaning rats, whereas, in adult females, PAH activity was only 42% that of males. Investigating hormonal influences on liver PAH activity we noted no change of enzyme activity following hydrocortisone, ACTH and estradiol treatment. However, 4 days of testosterone treatment in weaning female rats increased PAH activity (X1.7). Therefore, testosterone could explain increased PAH activity in adult males."}
{"id": "PMID:222975", "title": "Hormone action during aging: alterations and mechanisms.", "content": "The ability to respond to certain hormones is altered during the aging process. Attempts to elucidate the mechanisms involved in such changes have focused primarily on the various molecular components which mediate hormone actions. These include chromatin, the nucleus, cytoplasmic factors, adenylate cyclase and hormone receptors. Age related changes have been observed at all of these levels, and in some cases have been correlated with changes in biological responsiveness to particular hormones. This review attempts to summarize the data obtained in these studies. Possible interpretations are discussed and future directions for such research are suggested.", "contents": "Hormone action during aging: alterations and mechanisms. The ability to respond to certain hormones is altered during the aging process. Attempts to elucidate the mechanisms involved in such changes have focused primarily on the various molecular components which mediate hormone actions. These include chromatin, the nucleus, cytoplasmic factors, adenylate cyclase and hormone receptors. Age related changes have been observed at all of these levels, and in some cases have been correlated with changes in biological responsiveness to particular hormones. This review attempts to summarize the data obtained in these studies. Possible interpretations are discussed and future directions for such research are suggested."}
{"id": "PMID:222976", "title": "[Hormonal multiplicity of an apudoma of the lung and pancreas. Characterization of the different peptides in the tumoral extracts (author's transl)].", "content": "The capacity which the cells of some tumors have of synthesizing, storing, and releasing hormonal polypetides constitutes the basic characteristic of the neoplasms of the APUD system. On many occasions these polypeptides are released as hormonal precursors of high molecular weight, with a minimal biological action in comparison with the real hormone (big ACTH, big gastrin, etc.), and they have no clinical expressivity. On other occasions they reproduce, however, the clinical syndrome of the hormone released in excess. The production of multiple hormones by a single tumor is not a common event. Here we present the case of a patient with an oat-cell carcinoma of the lung and a carcinoma of the pancreas, both histopathologically primitive. In this patient a syndrome of inadequate secretion of antidiuretic hormone was detected. By means of radioimmunoassay techniques, the existence of antidiuretic hormone, ACTH with a predominance of the components of high molecular weight (big ACTH and beta-LPH) and MSH was demonstrated in the tumoral extracts from the lung, pancreas, and from a mediastinal metastatic lymph node. While the concentrations of ACTH were much greater in the lung than in the pancreas, the opposite occurred for the antidiuretic hormone. The synthesis of MSH by the hypophyseal gland or by tumors is not at present recognized, but rather is considered as a degradation product during the process of extraction. The APUD system makes up the morphologic substrate of the syndromes of familiar multiple endocrine adenomatosis. The present case could represent a variant of sporadic multiple endocrine neoplasms which would have the same anatomical basis.", "contents": "[Hormonal multiplicity of an apudoma of the lung and pancreas. Characterization of the different peptides in the tumoral extracts (author's transl)]. The capacity which the cells of some tumors have of synthesizing, storing, and releasing hormonal polypetides constitutes the basic characteristic of the neoplasms of the APUD system. On many occasions these polypeptides are released as hormonal precursors of high molecular weight, with a minimal biological action in comparison with the real hormone (big ACTH, big gastrin, etc.), and they have no clinical expressivity. On other occasions they reproduce, however, the clinical syndrome of the hormone released in excess. The production of multiple hormones by a single tumor is not a common event. Here we present the case of a patient with an oat-cell carcinoma of the lung and a carcinoma of the pancreas, both histopathologically primitive. In this patient a syndrome of inadequate secretion of antidiuretic hormone was detected. By means of radioimmunoassay techniques, the existence of antidiuretic hormone, ACTH with a predominance of the components of high molecular weight (big ACTH and beta-LPH) and MSH was demonstrated in the tumoral extracts from the lung, pancreas, and from a mediastinal metastatic lymph node. While the concentrations of ACTH were much greater in the lung than in the pancreas, the opposite occurred for the antidiuretic hormone. The synthesis of MSH by the hypophyseal gland or by tumors is not at present recognized, but rather is considered as a degradation product during the process of extraction. The APUD system makes up the morphologic substrate of the syndromes of familiar multiple endocrine adenomatosis. The present case could represent a variant of sporadic multiple endocrine neoplasms which would have the same anatomical basis."}
{"id": "PMID:222977", "title": "[Ectopic ACTH syndrome (author's transl)].", "content": "Ectopic ACTH syndrome is a clinicopathologic condition produced by certain tumors which release hormone that is indistinguishable from ACTH. It orginates the chemical and clinical anomalies characteristic of Cushing's syndrome by its action on the adrenal glands. The tumors may be present in any organ, though they are most frequently found in the lungs, thymus, pancreas or gastrointestinal tract. They may be benign or malignant, though usually the latter. Secretion of the hormone is completely autnomous; it is release in a way similar to that of the hypophysis. Not infrequently other hormones besides ACTH are also produced, such as MSH, serotonin, and CRF. Ectopic ACTH is of higher molecular weight than hypophyseal ACTH, which suggest it may be comprised of the latter bounded covalently to a peptide. The clinical course is rapid, so that not all of the symptoms of Cushing's syndrome develop. Moon face, osteoporosis, and obesity are typically lacking; melanodermia and hypokalemic alkalosis ofter appear. Laboratory data include an increase in ACTH and cholesterol concentrations, disappearance of the nictameral rhythm, and an increase in urinary excretion of 17-hydroxycorticoids and 17-ketosteroids. Stimulation and supression tests are abnormal. The prognosis is poor and the only possible treatment is a complete surgical removal of the tumor. Irradiation or chemotherapy could be applied as well as the correction of the adrenal hyperfunction by the administration of drugs or by total bilateral adrenalectomy.", "contents": "[Ectopic ACTH syndrome (author's transl)]. Ectopic ACTH syndrome is a clinicopathologic condition produced by certain tumors which release hormone that is indistinguishable from ACTH. It orginates the chemical and clinical anomalies characteristic of Cushing's syndrome by its action on the adrenal glands. The tumors may be present in any organ, though they are most frequently found in the lungs, thymus, pancreas or gastrointestinal tract. They may be benign or malignant, though usually the latter. Secretion of the hormone is completely autnomous; it is release in a way similar to that of the hypophysis. Not infrequently other hormones besides ACTH are also produced, such as MSH, serotonin, and CRF. Ectopic ACTH is of higher molecular weight than hypophyseal ACTH, which suggest it may be comprised of the latter bounded covalently to a peptide. The clinical course is rapid, so that not all of the symptoms of Cushing's syndrome develop. Moon face, osteoporosis, and obesity are typically lacking; melanodermia and hypokalemic alkalosis ofter appear. Laboratory data include an increase in ACTH and cholesterol concentrations, disappearance of the nictameral rhythm, and an increase in urinary excretion of 17-hydroxycorticoids and 17-ketosteroids. Stimulation and supression tests are abnormal. The prognosis is poor and the only possible treatment is a complete surgical removal of the tumor. Irradiation or chemotherapy could be applied as well as the correction of the adrenal hyperfunction by the administration of drugs or by total bilateral adrenalectomy."}
{"id": "PMID:222978", "title": "[Investigation of the hypoosmolal syndrome in carcinomas of the lung (author's transl)].", "content": "A study was performed on 30 patients diagnosed antomopathologically for malignant neoplasia of the lung (epidermoid carcinomas, adenocarcinomas, oat-cell carcinomas, and neoplasias which could not be definitely classified). The following parameters for blood and urine were determined: osmolality, sodium, potassium, urea, and creatinine. Osmotic free water, creatinine, sodium, and potassium clearances were also calculated, as well as the plasma osmolality/urinary osmolality ratio. The basic aim of our study was to investigate for the presence of disturbances in the metabolism of water and alterations in plasmatic and urinary osmolality in this type of tumor. These could appear as complete inadequate ADH secretion syndromes as discovered by Bartter and Schwartz or as incomplete syndromes (hypoosmolality and/or hyponatremia). Among the more significant results was the tendency toward oliguira seen in 44% of the patients and the high incidence of plasmatic hypoosmolality (31%). In three patients plasmatic hypoosmolality and hyponatremia were concommitant in repeated observations. A complete inadequate ADH secretion syndrome was discovered in another patient with an oat-cell carcinoma. He presented plasmatic hypoosmolality, hyponatremia, relative urinary hypertonia, and oliguria but not renal, suprarenal, or hepatic pathology.", "contents": "[Investigation of the hypoosmolal syndrome in carcinomas of the lung (author's transl)]. A study was performed on 30 patients diagnosed antomopathologically for malignant neoplasia of the lung (epidermoid carcinomas, adenocarcinomas, oat-cell carcinomas, and neoplasias which could not be definitely classified). The following parameters for blood and urine were determined: osmolality, sodium, potassium, urea, and creatinine. Osmotic free water, creatinine, sodium, and potassium clearances were also calculated, as well as the plasma osmolality/urinary osmolality ratio. The basic aim of our study was to investigate for the presence of disturbances in the metabolism of water and alterations in plasmatic and urinary osmolality in this type of tumor. These could appear as complete inadequate ADH secretion syndromes as discovered by Bartter and Schwartz or as incomplete syndromes (hypoosmolality and/or hyponatremia). Among the more significant results was the tendency toward oliguira seen in 44% of the patients and the high incidence of plasmatic hypoosmolality (31%). In three patients plasmatic hypoosmolality and hyponatremia were concommitant in repeated observations. A complete inadequate ADH secretion syndrome was discovered in another patient with an oat-cell carcinoma. He presented plasmatic hypoosmolality, hyponatremia, relative urinary hypertonia, and oliguria but not renal, suprarenal, or hepatic pathology."}
{"id": "PMID:222979", "title": "Tympanometry in the evaluation of vascular lesions of the middle ear and tinnitus of vascular origin.", "content": "The occurrence of vascular perturbations in the tympanogram in association with glomus tumors has previously been noted in the literature. We have broadened the scope of this method of diagnosis in the study of 3 glomus tympanicum and 3 glomus jugulare tumors, 1 dehiscent high jugular bulb, 1 aberrant carotid artery in the middle ear and 2 cases of pulsatile tinnitus of vascular origin. Analysis of illustrative tympanograms at standard and at increased sensitivity (x 20) obtained in these cases are presented. The following factors as they relate to the mechanism of recording the vascular perturbations are presented: air pressure and/or presence of fluid in the middle ear; compliance of the tympanic membrane and ossicular chain as affected by the mass, size and degree of vascularity of the mass and presence of extraneous sounds. A new method of recording the vascular perturbations utilizing a time-base generator affixed to an X-Y plotter is described. It is the purpose of this study to demonstrate the utility of obtaining tympanograms at standard and at increased sensitivity in the evaluation of vascular middle ear lesions and tinnitus of vascular origin.", "contents": "Tympanometry in the evaluation of vascular lesions of the middle ear and tinnitus of vascular origin. The occurrence of vascular perturbations in the tympanogram in association with glomus tumors has previously been noted in the literature. We have broadened the scope of this method of diagnosis in the study of 3 glomus tympanicum and 3 glomus jugulare tumors, 1 dehiscent high jugular bulb, 1 aberrant carotid artery in the middle ear and 2 cases of pulsatile tinnitus of vascular origin. Analysis of illustrative tympanograms at standard and at increased sensitivity (x 20) obtained in these cases are presented. The following factors as they relate to the mechanism of recording the vascular perturbations are presented: air pressure and/or presence of fluid in the middle ear; compliance of the tympanic membrane and ossicular chain as affected by the mass, size and degree of vascularity of the mass and presence of extraneous sounds. A new method of recording the vascular perturbations utilizing a time-base generator affixed to an X-Y plotter is described. It is the purpose of this study to demonstrate the utility of obtaining tympanograms at standard and at increased sensitivity in the evaluation of vascular middle ear lesions and tinnitus of vascular origin."}
{"id": "PMID:222991", "title": "The composition and metabolism of high density lipoprotein subfractions.", "content": "The composition and metabolism of high density lipoprotein (HDL) subfractions were investigated in seven normal individuals. Mean HDL2 (d, 1.063-1.125 g/ml) composition (by weight) was 43% protein, 28% phospholipid, 23% cholesterol, and 6% triglyceride, and mean HDL3 (d, 1.125-1.21 g/ml) composition was 58% protein, 22% phospholipid, 14% cholesterol, and 5% triglyceride. The mean apoA-I; apoA-II weight ratio was 4.75 for HDL2 and 3.65 for HDL3. HDL2 protein was proportionally slightly richer in C apolipoproteins and higher molecular weight constituents (including apoE) than HDL3. Kinetic studies utilized radiolabeled HDLA (d, 1.09-1.21 g/ml), HDL2, and HDL3 demonstrated rapid exchange of apoA-I and apoA-II radioactivity among HDL subfractions, similar fractional rates of catabolism of apoA-I and apo A-II within HDL, and similar radioactivity decay within HDL subfractions. Mean plasma residence time  was 5.74 days for radiolabeled HDL2 and 5.70 days for radiolabedled HDL3. Differences in HDL protein mass among individuals were largely due to alterations in catabolism, and in general both HDL2 and HDL3 were catabolized via a plasma and a nonplasma pathway. Data from simultaneous radiolabeled very low density lipoprotein and HDL studies in 2 individuals are consistent with the concept that apoC-II and apoC-III are catabolized at a different rate than are apo A-I and apo A-II within the HDL density range.", "contents": "The composition and metabolism of high density lipoprotein subfractions. The composition and metabolism of high density lipoprotein (HDL) subfractions were investigated in seven normal individuals. Mean HDL2 (d, 1.063-1.125 g/ml) composition (by weight) was 43% protein, 28% phospholipid, 23% cholesterol, and 6% triglyceride, and mean HDL3 (d, 1.125-1.21 g/ml) composition was 58% protein, 22% phospholipid, 14% cholesterol, and 5% triglyceride. The mean apoA-I; apoA-II weight ratio was 4.75 for HDL2 and 3.65 for HDL3. HDL2 protein was proportionally slightly richer in C apolipoproteins and higher molecular weight constituents (including apoE) than HDL3. Kinetic studies utilized radiolabeled HDLA (d, 1.09-1.21 g/ml), HDL2, and HDL3 demonstrated rapid exchange of apoA-I and apoA-II radioactivity among HDL subfractions, similar fractional rates of catabolism of apoA-I and apo A-II within HDL, and similar radioactivity decay within HDL subfractions. Mean plasma residence time  was 5.74 days for radiolabeled HDL2 and 5.70 days for radiolabedled HDL3. Differences in HDL protein mass among individuals were largely due to alterations in catabolism, and in general both HDL2 and HDL3 were catabolized via a plasma and a nonplasma pathway. Data from simultaneous radiolabeled very low density lipoprotein and HDL studies in 2 individuals are consistent with the concept that apoC-II and apoC-III are catabolized at a different rate than are apo A-I and apo A-II within the HDL density range."}
{"id": "PMID:222992", "title": "Plasma lipoprotein changes in suckling and weanling rabbits fed semipurified diets.", "content": "The distribution and composition of the plasma lipoproteins were studied in suckling rabbits and in rabbits either weaned to or fed as young adults cholesterol-free, semipurified diets containing protein of animal (casein) or plant (soy protein isolate) origin. The raised cholesterol levels of the suckling period resulted in an increase of very low density and intermediate density lipoproteins in a making similar to that seen in adult rabbits fed a high fat diet supplemented with cholesterol. Young rabbits fed the cholesterol-free, semipurified, diet containing casein also became hypercholesterolemic but, in this case, the increased cholesterol was found primarily in lipoproteins of intermediate density. Cholesterol levels remained low in those rabbits fed the soy protein isolate diet, and the lipoprotein distribution was somewhat similar to that of chow-fed animals. It appears that the raised cholesterol levels during the suckling period result in different lipoprotein patterns to those produced in young adult animals by a cholesterol-free, semipurified diet.", "contents": "Plasma lipoprotein changes in suckling and weanling rabbits fed semipurified diets. The distribution and composition of the plasma lipoproteins were studied in suckling rabbits and in rabbits either weaned to or fed as young adults cholesterol-free, semipurified diets containing protein of animal (casein) or plant (soy protein isolate) origin. The raised cholesterol levels of the suckling period resulted in an increase of very low density and intermediate density lipoproteins in a making similar to that seen in adult rabbits fed a high fat diet supplemented with cholesterol. Young rabbits fed the cholesterol-free, semipurified, diet containing casein also became hypercholesterolemic but, in this case, the increased cholesterol was found primarily in lipoproteins of intermediate density. Cholesterol levels remained low in those rabbits fed the soy protein isolate diet, and the lipoprotein distribution was somewhat similar to that of chow-fed animals. It appears that the raised cholesterol levels during the suckling period result in different lipoprotein patterns to those produced in young adult animals by a cholesterol-free, semipurified diet."}
{"id": "PMID:223019", "title": "A common pathophysiology for sudden cot death and sleep apnoea. \"The vacuum-glossoptosis syndrome\".", "content": "Several congenital and acquired conditions, characterized by upper airway narrowing, may result in respiratory, cardiac, and sleep disturbances. In all these conditions the leading clinical feature is the occurrence of cyclic obstructive apnoea, mainly during sleep. The common pathogenic mechanism for the airway occlusion seems to be a backward displacement of the tongue and mandible, favoured by the muscle relaxation which occurs during sleep and by gravity in the supine position. A constant factor determining the glossoptosis is the pharyngeal vacuum occurring in these conditions as a result of inspiratory efforts in face of a narrowed upper airway. The response to this type of obstruction is age-dependent, since only in early infancy may these apnoeic spells be life-threatening. A similar pathophysiology is suggested for sudden cot death, which could be considered as a peculiar presentation of this \"vacuum-glossoptosis syndrome\". This hypothesis could explain why sudden cot death is often associated with nasopharyngitis and occurs always in infancy, almost invariably during sleep.", "contents": "A common pathophysiology for sudden cot death and sleep apnoea. \"The vacuum-glossoptosis syndrome\". Several congenital and acquired conditions, characterized by upper airway narrowing, may result in respiratory, cardiac, and sleep disturbances. In all these conditions the leading clinical feature is the occurrence of cyclic obstructive apnoea, mainly during sleep. The common pathogenic mechanism for the airway occlusion seems to be a backward displacement of the tongue and mandible, favoured by the muscle relaxation which occurs during sleep and by gravity in the supine position. A constant factor determining the glossoptosis is the pharyngeal vacuum occurring in these conditions as a result of inspiratory efforts in face of a narrowed upper airway. The response to this type of obstruction is age-dependent, since only in early infancy may these apnoeic spells be life-threatening. A similar pathophysiology is suggested for sudden cot death, which could be considered as a peculiar presentation of this \"vacuum-glossoptosis syndrome\". This hypothesis could explain why sudden cot death is often associated with nasopharyngitis and occurs always in infancy, almost invariably during sleep."}
{"id": "PMID:223021", "title": "Theoretical mechanisms for synthesis of carcinogen-induced embryonic proteins: IV. The viruses.", "content": "Speculations are developed for a mechanism by which oncogenic viruses can induce alterations in cells allowing them to express embryonic genes. It is suggested that if viral deoxyribonucleic acid, directly or via ribonucleic acid directed deoxyribonucleic acid polymerase activity becomes inserted at particular euchromatin - heterochromatin junctions of quasidifferentiated stem-like cells, then deheterochromatization may result, causing in turn derepression of genes for acidic protein phosphokinases. This sets into motion a series of events including altered acid protein repressors of embryonic genes which are repressed by uniquely weak type repressors. This explains how viruses can act as specific embryonic gene-inducing agents similar to chemical inducing agents such as the hepatocarcinogen ethinine.", "contents": "Theoretical mechanisms for synthesis of carcinogen-induced embryonic proteins: IV. The viruses. Speculations are developed for a mechanism by which oncogenic viruses can induce alterations in cells allowing them to express embryonic genes. It is suggested that if viral deoxyribonucleic acid, directly or via ribonucleic acid directed deoxyribonucleic acid polymerase activity becomes inserted at particular euchromatin - heterochromatin junctions of quasidifferentiated stem-like cells, then deheterochromatization may result, causing in turn derepression of genes for acidic protein phosphokinases. This sets into motion a series of events including altered acid protein repressors of embryonic genes which are repressed by uniquely weak type repressors. This explains how viruses can act as specific embryonic gene-inducing agents similar to chemical inducing agents such as the hepatocarcinogen ethinine."}
{"id": "PMID:223022", "title": "The cause of species differences in mammary tumourigenesis: significance of mammary gland DNA synthesis.", "content": "The causes of species differences in mammary tumourigenesis are briefly discussed from the genetical and environmental points of view, although no firm conclusions can be drawn. Distinct differences in mammary gland DNA synthesis were found between female mice and rats, which behave very differently in mammary tumourigenesis. Based on the importance of mammary gland DNA synthesis in mammary tumourigenesis, the differences in mammary gland DNA synthesis between species is hypothesized to be a major cause of the species differences in mammary tumourigenesis.", "contents": "The cause of species differences in mammary tumourigenesis: significance of mammary gland DNA synthesis. The causes of species differences in mammary tumourigenesis are briefly discussed from the genetical and environmental points of view, although no firm conclusions can be drawn. Distinct differences in mammary gland DNA synthesis were found between female mice and rats, which behave very differently in mammary tumourigenesis. Based on the importance of mammary gland DNA synthesis in mammary tumourigenesis, the differences in mammary gland DNA synthesis between species is hypothesized to be a major cause of the species differences in mammary tumourigenesis."}
{"id": "PMID:223026", "title": "Plasma protein regulation of platelet function and metabolism.", "content": "This reviews summarizes our evidence suggesting that the plasma protein enviroment influences platelet aggregation potential and metabolic activity. Cationic proteins are capable of restoring the aggreation potential of washed human platelets. The aggregation restoring effect of gamma globulin is inhibited by more anionic proteins in subfractions of Cohn fraction IV and fractions V and VI. Artificial enhancement of the net negative charge of plasma proteins through acylation produces derivatives capable of inhibiting platelet rich plasma. The oxygen consumption of washed human platelets is lower than in platelet rich plasma while the lactate production is identical. Autologus plasma, albumin or IgG immunoglobulin restores the oxygen consumption of washed platelets to values comparable to those obtained for platelet rich plasma, while the lactate production is unaffected. Fibrinogen on IgA myeloma protein increases the lactate production, but not the oxygen consumption. Cyclic AMP levels are considerably lower in washed platelets than in platelet rich plasma. Gamma globulin and albumin causes a futher decrease, which is progressive with time. Fibrinogen causes no change in platelet cyclic AMP content. It is suggested that these observations may in part be explained by the equilibriun between anionic and cationic proteins in the platelet microenvironment. This hypothesis appears applicable in certain situations.", "contents": "Plasma protein regulation of platelet function and metabolism. This reviews summarizes our evidence suggesting that the plasma protein enviroment influences platelet aggregation potential and metabolic activity. Cationic proteins are capable of restoring the aggreation potential of washed human platelets. The aggregation restoring effect of gamma globulin is inhibited by more anionic proteins in subfractions of Cohn fraction IV and fractions V and VI. Artificial enhancement of the net negative charge of plasma proteins through acylation produces derivatives capable of inhibiting platelet rich plasma. The oxygen consumption of washed human platelets is lower than in platelet rich plasma while the lactate production is identical. Autologus plasma, albumin or IgG immunoglobulin restores the oxygen consumption of washed platelets to values comparable to those obtained for platelet rich plasma, while the lactate production is unaffected. Fibrinogen on IgA myeloma protein increases the lactate production, but not the oxygen consumption. Cyclic AMP levels are considerably lower in washed platelets than in platelet rich plasma. Gamma globulin and albumin causes a futher decrease, which is progressive with time. Fibrinogen causes no change in platelet cyclic AMP content. It is suggested that these observations may in part be explained by the equilibriun between anionic and cationic proteins in the platelet microenvironment. This hypothesis appears applicable in certain situations."}
{"id": "PMID:223025", "title": "Cytochrome P450 in adrenocortical mitochondria.", "content": "Cytochrome P450 in the mitochondria of the adrenal cortex functions in the monooxygenation reactions for the biosynthesis of various steroid hormones, such as cholesterol side chain cleavage, hydroxylation at 11 beta-position and that at 18-position of the steroid structure. The cytochrome is firmly associated with the mitochondrial membrane and therefore can be isolated only by the aid of ionic or non-ionic detergent. Recently, two cytochromes P450 each catalyzing a specified reaction have been purified to a homogeneous state, that is, P450scc having cholesterol side chain cleavage activity and P45011 beta having 11 beta-hydroxylation activity. The properties of these purified P450's as well as the other components of the monooxygenase system, adrenodoxin and adrenodoxin reductase, are, therefore, summarized and compared to those of P450 in the mitochondrial preparation in situ. Among many findings, both purified cytochromes P450 were revealed to be a low-spin type hemoprotein and their spin states were changed to a high-spin state by being complexed with the corresponding substrate. The binding of a substrate also facilitated the reduction of the cytochrome and appeared to increase the stability of the oxygenated form of cytochrome P450. These effects are important from the point of view that the primary role of the heme of cytochrome P450 is the activation of molecular oxygen. In addition, the results of our detailed kinetic studies on the transfer of electrons from adrenodoxin to cytochrome P450 in the reconstituted system have also been described. Finally, the topology of adrenodoxin and the reductase were shown to be on the inner mitochondrial membrane by a peroxidase-labeled antibody method.", "contents": "Cytochrome P450 in adrenocortical mitochondria. Cytochrome P450 in the mitochondria of the adrenal cortex functions in the monooxygenation reactions for the biosynthesis of various steroid hormones, such as cholesterol side chain cleavage, hydroxylation at 11 beta-position and that at 18-position of the steroid structure. The cytochrome is firmly associated with the mitochondrial membrane and therefore can be isolated only by the aid of ionic or non-ionic detergent. Recently, two cytochromes P450 each catalyzing a specified reaction have been purified to a homogeneous state, that is, P450scc having cholesterol side chain cleavage activity and P45011 beta having 11 beta-hydroxylation activity. The properties of these purified P450's as well as the other components of the monooxygenase system, adrenodoxin and adrenodoxin reductase, are, therefore, summarized and compared to those of P450 in the mitochondrial preparation in situ. Among many findings, both purified cytochromes P450 were revealed to be a low-spin type hemoprotein and their spin states were changed to a high-spin state by being complexed with the corresponding substrate. The binding of a substrate also facilitated the reduction of the cytochrome and appeared to increase the stability of the oxygenated form of cytochrome P450. These effects are important from the point of view that the primary role of the heme of cytochrome P450 is the activation of molecular oxygen. In addition, the results of our detailed kinetic studies on the transfer of electrons from adrenodoxin to cytochrome P450 in the reconstituted system have also been described. Finally, the topology of adrenodoxin and the reductase were shown to be on the inner mitochondrial membrane by a peroxidase-labeled antibody method."}
{"id": "PMID:223027", "title": "mRNP proteins, initiation factors and phosphorylation.", "content": "Information has been collected to stimulate interest regarding the nature and the possible role of mRNP protein phosphorylation in a cytoplasmic control mechanism for protein synthesis. It does not imply a direct relationship between mRNP protein and initiation factors. These proteins have some properties in common (e.g. molecular weight, phosphorylation, protein kinase, mRNA binding activity). We emphasize that some free mRNP may be translatable after modification of their protein by interference factors belonging to other cellular compartments. Thus, some mRNP proteins might possess initiation factor or protein synthetic activity if we accept Spirin's theory, i.e., \"Eukaryotic messenger RNA and informosomes omnia mea mecum porto.", "contents": "mRNP proteins, initiation factors and phosphorylation. Information has been collected to stimulate interest regarding the nature and the possible role of mRNP protein phosphorylation in a cytoplasmic control mechanism for protein synthesis. It does not imply a direct relationship between mRNP protein and initiation factors. These proteins have some properties in common (e.g. molecular weight, phosphorylation, protein kinase, mRNA binding activity). We emphasize that some free mRNP may be translatable after modification of their protein by interference factors belonging to other cellular compartments. Thus, some mRNP proteins might possess initiation factor or protein synthetic activity if we accept Spirin's theory, i.e., \"Eukaryotic messenger RNA and informosomes omnia mea mecum porto."}
{"id": "PMID:223028", "title": "[Virus-specific proteins associated with components of protein-synthesizing systems in Krebs II ascites carcinoma cells infected with encephalomyocarditis virus].", "content": "Extracts from encephalomyocarditis (EMS) virus infected Krebs II ascites carcinoma cells pulse-labeled during the active virus-specific synthesis and then chased were fractionated in a sucrose concentration gradient. It has shown that some radioactivity was detectable in the polysome region as well as in the regions of ribosome monomers and ribosomal subunits. An analysis of the radioactive material in a CsCl density gradient and by polyacrylamide gel electrophoresis has shown that components of the protein-synthesizing system in infected cells are bound to some proteins, the electrophoretic mobility of which corresponds to that of polypeptides found in the infected cells, namely, polypeptides G 16 (18 kdalton) and 22 (22 kdalton). The ribosomes from normal cells were also found to be associated with three labeled polypeptides, their molecular weight (89-90, 43-48 and 39-40 kdalton) being different from those of the polypeptides bound to the ribosomes from the infected cells. Thus, the presence of polypeptides G and 22 is specific for ribosomes isolated from the infected cells. The possible significance of this binding is discussed.", "contents": "[Virus-specific proteins associated with components of protein-synthesizing systems in Krebs II ascites carcinoma cells infected with encephalomyocarditis virus]. Extracts from encephalomyocarditis (EMS) virus infected Krebs II ascites carcinoma cells pulse-labeled during the active virus-specific synthesis and then chased were fractionated in a sucrose concentration gradient. It has shown that some radioactivity was detectable in the polysome region as well as in the regions of ribosome monomers and ribosomal subunits. An analysis of the radioactive material in a CsCl density gradient and by polyacrylamide gel electrophoresis has shown that components of the protein-synthesizing system in infected cells are bound to some proteins, the electrophoretic mobility of which corresponds to that of polypeptides found in the infected cells, namely, polypeptides G 16 (18 kdalton) and 22 (22 kdalton). The ribosomes from normal cells were also found to be associated with three labeled polypeptides, their molecular weight (89-90, 43-48 and 39-40 kdalton) being different from those of the polypeptides bound to the ribosomes from the infected cells. Thus, the presence of polypeptides G and 22 is specific for ribosomes isolated from the infected cells. The possible significance of this binding is discussed."}
{"id": "PMID:223029", "title": "[Interaction of steroids with human serum albumin by spin echo technique and paramagnetic sound methods].", "content": "The rate of water proton relaxation of the solutions of human serum albumin (HSA) modified by different spin labels has been investigated by spin echo technique. The rate of proton relaxation in the presence of the labeled HSA is higher than that in water solutions of spin labels. The proton relaxation data of the protein solutions can be explained by local properties of the water, bound with the protein (in the regions of spin labels) which seem to resemble those of water-glycerol solutions. The rate of proton relaxation was decreased in the presence of steroids that can be explained by a decrease of the local microviscosity of the water-protein matrix due to interaction of steroids with HSA.", "contents": "[Interaction of steroids with human serum albumin by spin echo technique and paramagnetic sound methods]. The rate of water proton relaxation of the solutions of human serum albumin (HSA) modified by different spin labels has been investigated by spin echo technique. The rate of proton relaxation in the presence of the labeled HSA is higher than that in water solutions of spin labels. The proton relaxation data of the protein solutions can be explained by local properties of the water, bound with the protein (in the regions of spin labels) which seem to resemble those of water-glycerol solutions. The rate of proton relaxation was decreased in the presence of steroids that can be explained by a decrease of the local microviscosity of the water-protein matrix due to interaction of steroids with HSA."}
{"id": "PMID:223030", "title": "[Study of DNA-dye interaction by spin-labels].", "content": "The binding of ethidium bromide and acriflavin dyes with DNA modified with a spin-labelled analogue of ethylene imine has been studied. These spin-labels were shown to bind covalently to DNA, at the same time the number of the dye molecules bound is decreased without any changes in the binding constant. Analysis of ESR spectra of the samples in the frozen 50% water-glycerol solution at 77 degrees K for spin-labelled DNA has shown that addition of the dyes increases distance between the labels. This fact might be explained by an increase in DNA length upon formation of the complex with dye molecules.", "contents": "[Study of DNA-dye interaction by spin-labels]. The binding of ethidium bromide and acriflavin dyes with DNA modified with a spin-labelled analogue of ethylene imine has been studied. These spin-labels were shown to bind covalently to DNA, at the same time the number of the dye molecules bound is decreased without any changes in the binding constant. Analysis of ESR spectra of the samples in the frozen 50% water-glycerol solution at 77 degrees K for spin-labelled DNA has shown that addition of the dyes increases distance between the labels. This fact might be explained by an increase in DNA length upon formation of the complex with dye molecules."}
{"id": "PMID:223033", "title": "[Macromolecule rotative correlation time measurement by ESR for covalently bound spin label].", "content": "The dependence from temperature and viscosity of the shifts of the internal and external wide extremums in the ESR spectra of spin labelled bovine serum albumin has been studied. 2,2,6,6-tetramethylpiperidine-NI-oxyl-4-iodacetamide was used as a spin label. The obtained dependences was shown to be a consequence of the label participation in two types of rotations: an anisotropic fast rotation with tau less than 10(-9) sec relatively to a macromolecule, and the isotropic one with tau greater than 10(-8) sec due to rotation of the macromolecule itself. These conclusions were done on the basis of a model for complex rotation of the spin label. Comparison of theoretical and experimental data makes it possible to determined the correlation time for the protein moiety, to evaluate quantitatively the polarity of surroundings of the iminoxyl and to introduce a numerical parameter for the degree of mobility of the spin label relatively to protein molecule.", "contents": "[Macromolecule rotative correlation time measurement by ESR for covalently bound spin label]. The dependence from temperature and viscosity of the shifts of the internal and external wide extremums in the ESR spectra of spin labelled bovine serum albumin has been studied. 2,2,6,6-tetramethylpiperidine-NI-oxyl-4-iodacetamide was used as a spin label. The obtained dependences was shown to be a consequence of the label participation in two types of rotations: an anisotropic fast rotation with tau less than 10(-9) sec relatively to a macromolecule, and the isotropic one with tau greater than 10(-8) sec due to rotation of the macromolecule itself. These conclusions were done on the basis of a model for complex rotation of the spin label. Comparison of theoretical and experimental data makes it possible to determined the correlation time for the protein moiety, to evaluate quantitatively the polarity of surroundings of the iminoxyl and to introduce a numerical parameter for the degree of mobility of the spin label relatively to protein molecule."}
{"id": "PMID:223034", "title": "[Influence of histone kinase phosphorylating lysine-rich histones, on the physico-chemical properties of normal hepatocyte chromatin and after partial hepatectomy].", "content": "The influence of a specific histone kinase, phosphorylating lysin-rich histone H1, H2a, H2b on the physico-chemical properties of chromatin from hepatocytes of normal and hepatectomized guinea pigs has been investigated. A cytochemical method has been used which permits to obtain information about the physico-chemical properties of the chromatin in situ, i.e. without its isolation. This approach allows us to evaluate changes in chromatin properties in cell cultures as well as in the intact organism. It is found that the specific histone kinase changes the properties of chromatin in non-dividing cells bringing about an increase of acridine orange binding to the level characteristic for hepatocytes after partial hepatectomy. At the same time the chromatin properties in activated hepatocytes are not changed under the action of the histone kinase. It is concluded that the specific histone kinase, phosphorylating lysine-rich histones can play an important role in the course of chromatin activation in cells stimulated to proliferation.", "contents": "[Influence of histone kinase phosphorylating lysine-rich histones, on the physico-chemical properties of normal hepatocyte chromatin and after partial hepatectomy]. The influence of a specific histone kinase, phosphorylating lysin-rich histone H1, H2a, H2b on the physico-chemical properties of chromatin from hepatocytes of normal and hepatectomized guinea pigs has been investigated. A cytochemical method has been used which permits to obtain information about the physico-chemical properties of the chromatin in situ, i.e. without its isolation. This approach allows us to evaluate changes in chromatin properties in cell cultures as well as in the intact organism. It is found that the specific histone kinase changes the properties of chromatin in non-dividing cells bringing about an increase of acridine orange binding to the level characteristic for hepatocytes after partial hepatectomy. At the same time the chromatin properties in activated hepatocytes are not changed under the action of the histone kinase. It is concluded that the specific histone kinase, phosphorylating lysine-rich histones can play an important role in the course of chromatin activation in cells stimulated to proliferation."}
{"id": "PMID:223031", "title": "[Investigation of myxovirus structure by spin probes. I. Thermostability of the lipid membrane of influenza and Sendai viruses].", "content": "Electron spin resonance (ESR) spectra of the spin probes C5 and C16, the iminoxyl derivatives of stearic acids, have been investigated after their incorporation into lipid membranes of influenza and Sendai viruses. At room temperature the spectra of both probes coincided indicating the similar composition and origin of lipid viral membranes. Similar to influenza virus, Sendai virus was shown to possess the external lipid bilayer. Investigation of the rigidity of the lipid phase of myxoviruses as a function temperature has shown that the structure of the lipid external layer (no less than 8 A in thickness) is due to surface glycoproteins incorporated into the viral membrane. The structural transition of the lipid phase of influenza and Sendai viruses 8 A apart from the viral surface was observed at 50 degrees C. The surface glycoproteins do not probably penetrate deep in the lipid membrane of myxoviruses and do not condition its structure at long distances (22 A) from the viral surface. The completely reversible structural transition of lipid phase at this distance was observed at temperatures 17--20 degrees C.", "contents": "[Investigation of myxovirus structure by spin probes. I. Thermostability of the lipid membrane of influenza and Sendai viruses]. Electron spin resonance (ESR) spectra of the spin probes C5 and C16, the iminoxyl derivatives of stearic acids, have been investigated after their incorporation into lipid membranes of influenza and Sendai viruses. At room temperature the spectra of both probes coincided indicating the similar composition and origin of lipid viral membranes. Similar to influenza virus, Sendai virus was shown to possess the external lipid bilayer. Investigation of the rigidity of the lipid phase of myxoviruses as a function temperature has shown that the structure of the lipid external layer (no less than 8 A in thickness) is due to surface glycoproteins incorporated into the viral membrane. The structural transition of the lipid phase of influenza and Sendai viruses 8 A apart from the viral surface was observed at 50 degrees C. The surface glycoproteins do not probably penetrate deep in the lipid membrane of myxoviruses and do not condition its structure at long distances (22 A) from the viral surface. The completely reversible structural transition of lipid phase at this distance was observed at temperatures 17--20 degrees C."}
{"id": "PMID:223035", "title": "[Photoreduction of hemoglobin in erythrocytes].", "content": "The ability of the erythrocyte membrane to transfer the reducing equivalent from the outer solution into the cells was studied. Erythrocyte hemoglobin transformed into the metstate serves as the electron acceptor. The donors develop during illuminating with visible light the outer solution, containing NADH and eosin. Some precautions were made to inhibit the migration of the donor molecules through the membrane. The photoreduction of hemoglobin in erythrocytes in such conditions can be attributed to the diffusion of some lipophilic electron carriers if they exist in the membrane, or to the ability of the transmembrane proteins to mediate the electron transfer from definite donors to the acceptors.", "contents": "[Photoreduction of hemoglobin in erythrocytes]. The ability of the erythrocyte membrane to transfer the reducing equivalent from the outer solution into the cells was studied. Erythrocyte hemoglobin transformed into the metstate serves as the electron acceptor. The donors develop during illuminating with visible light the outer solution, containing NADH and eosin. Some precautions were made to inhibit the migration of the donor molecules through the membrane. The photoreduction of hemoglobin in erythrocytes in such conditions can be attributed to the diffusion of some lipophilic electron carriers if they exist in the membrane, or to the ability of the transmembrane proteins to mediate the electron transfer from definite donors to the acceptors."}
{"id": "PMID:223032", "title": "[Structure of higher plant chloroplast membranes as studied by paramagnetic probes].", "content": "A study of interaction between ten different spin labels and bean chloroplast membranes was carried out. It was found that spin labels were localized in three characteristic regions of the membrane. These regions differ in density and mode of the lipids package. The processes of light--induced reduction (with loss of paramagnetism) and reoxidation of spin labels are due to the interaction with the components of electron-transport chain between photosystems I and II. The kinetics of redox-changes of spin labels depends on the site of the paramagnetic fragment location in membrane.", "contents": "[Structure of higher plant chloroplast membranes as studied by paramagnetic probes]. A study of interaction between ten different spin labels and bean chloroplast membranes was carried out. It was found that spin labels were localized in three characteristic regions of the membrane. These regions differ in density and mode of the lipids package. The processes of light--induced reduction (with loss of paramagnetism) and reoxidation of spin labels are due to the interaction with the components of electron-transport chain between photosystems I and II. The kinetics of redox-changes of spin labels depends on the site of the paramagnetic fragment location in membrane."}
{"id": "PMID:223036", "title": "[Nuclear magnetic resonance study of the conformation in nucleotides, oligonucleotides, and their analogs. I. Conformation of adenosine-3',5'-cyclic phosphate and its analogs in aqueous solutions].", "content": "Conformation in aqueous solution of adenosine-3',5'-cyclophosphate, 8-(beta-aminoethylamino) adenosine-3',5'-cyclophosphate, 8-(beta-oxiethylamino) adenosine-3',5'-cyclophosphate, 8-(carboxymethylamino) adenosine-3',5'-cyclophosphate and their non-cyclic analogs has been studied by NMR spectroscopy. The conformational situation in the model of dynamic equilibrium of sin- and anti-states has been described on the basis of spinlattice relaxation times and temperature dependences of chemical shifts. Adenosine-3',5'-cyclophosphate has been demonstrated to exist mainly in anti-conformation while 8-substituted analogs -- in sin-conformation. Equilibrium constants have been calculated for the compounds under study.", "contents": "[Nuclear magnetic resonance study of the conformation in nucleotides, oligonucleotides, and their analogs. I. Conformation of adenosine-3',5'-cyclic phosphate and its analogs in aqueous solutions]. Conformation in aqueous solution of adenosine-3',5'-cyclophosphate, 8-(beta-aminoethylamino) adenosine-3',5'-cyclophosphate, 8-(beta-oxiethylamino) adenosine-3',5'-cyclophosphate, 8-(carboxymethylamino) adenosine-3',5'-cyclophosphate and their non-cyclic analogs has been studied by NMR spectroscopy. The conformational situation in the model of dynamic equilibrium of sin- and anti-states has been described on the basis of spinlattice relaxation times and temperature dependences of chemical shifts. Adenosine-3',5'-cyclophosphate has been demonstrated to exist mainly in anti-conformation while 8-substituted analogs -- in sin-conformation. Equilibrium constants have been calculated for the compounds under study."}
{"id": "PMID:223037", "title": "[Investigation of the microstructure of biological systems by triplet label].", "content": "A method for investigating the microstruct and dynamics of biological systems by means of triplet-excited molecules is suggested. The method is based on the phenomenon of triplet excitation disactivation by exchange-resonance triplet-triplet energy transfer to the acceptor or by intercombination conversion induced by interaction of an excited molecule with a paramagnetic center. The disactivation efficiency was measured by registrating the phosphorescense decay kinetics. The interaction of the triplet label eosin isothiocyanate, covalently coupled with albumine, lysozyme, sarcoplasmic reticulum membrane and Ca-Mg-dependent sarcoplasmic reticulum ATPase, with O2, the stable nitroxide radicals and ions of Mn2+ was investigated to analyse the potentialities of this method. As a model system the eosin phosphorescence quenching by the same quenchers in glycerine-aguaous solutions was studied. The method permits to investigate the microviscosity and microstructure of biological objects in the label attached region on interaction of the label with a sound-quencher with constants being 10(4) divided by 10(9) M-1 sec-1 and to measure the lateral diffusion of molecules in highly viscosity media (10 divided by 10(5) santypuas).", "contents": "[Investigation of the microstructure of biological systems by triplet label]. A method for investigating the microstruct and dynamics of biological systems by means of triplet-excited molecules is suggested. The method is based on the phenomenon of triplet excitation disactivation by exchange-resonance triplet-triplet energy transfer to the acceptor or by intercombination conversion induced by interaction of an excited molecule with a paramagnetic center. The disactivation efficiency was measured by registrating the phosphorescense decay kinetics. The interaction of the triplet label eosin isothiocyanate, covalently coupled with albumine, lysozyme, sarcoplasmic reticulum membrane and Ca-Mg-dependent sarcoplasmic reticulum ATPase, with O2, the stable nitroxide radicals and ions of Mn2+ was investigated to analyse the potentialities of this method. As a model system the eosin phosphorescence quenching by the same quenchers in glycerine-aguaous solutions was studied. The method permits to investigate the microviscosity and microstructure of biological objects in the label attached region on interaction of the label with a sound-quencher with constants being 10(4) divided by 10(9) M-1 sec-1 and to measure the lateral diffusion of molecules in highly viscosity media (10 divided by 10(5) santypuas)."}
{"id": "PMID:223075", "title": "[Effectivess of synaptic influences of the ascending tracts of different spinal cord funiculi on reticulospinal neurons in cats].", "content": "Extracellular recording of the responses of the reticulospinal neurons evoked by stimulation of the dorsal, dorsolateral, ventral and ventrolateral spinal funiculi were performed in cats under chloralose anesthesia. It is found that dorsal funiculi of the spinal cord are an effective source of ascending influences on the reticulospinal neurons. Correlation of synaptic responses of the reticulospinal neurons with antidromatic responses in the peripheral nerves set up by stimulation of the dorsal funiculi shows that the former can be evoked by low threshold muscle (groups I and II) and cutaneous (group II) afferent fibres. The role of the ascending tracts in the transmission of the spino-bulbo-spinal activity is discussed.", "contents": "[Effectivess of synaptic influences of the ascending tracts of different spinal cord funiculi on reticulospinal neurons in cats]. Extracellular recording of the responses of the reticulospinal neurons evoked by stimulation of the dorsal, dorsolateral, ventral and ventrolateral spinal funiculi were performed in cats under chloralose anesthesia. It is found that dorsal funiculi of the spinal cord are an effective source of ascending influences on the reticulospinal neurons. Correlation of synaptic responses of the reticulospinal neurons with antidromatic responses in the peripheral nerves set up by stimulation of the dorsal funiculi shows that the former can be evoked by low threshold muscle (groups I and II) and cutaneous (group II) afferent fibres. The role of the ascending tracts in the transmission of the spino-bulbo-spinal activity is discussed."}
{"id": "PMID:223076", "title": "Action of harmaline and diazepam on the cerebellar content of cyclic GMP and on the activities of two endogenous inhibitors of protein kinase.", "content": "The rat cerebellum contains a significant amount of cGMP-dependent protein kinase, cAMP-dependent and cyclic nucleotide-independent protein kinase, and a large concentration of protein kinase inhibitors. These inhibitors are thermostable proteins which can be separated by gel chromatography into two molecular forms: the type 1 and type 2 inhibitors of protein kinase (14). The type 1 inhibitor blocks the rat cerebellar cAMP-dependent protein kinase activity while the type 2 inhibitor blocks the cGMP-dependent protein kinase, the cAMP-dependent protein kinase, and the cyclic nucleotide-independent protein kinases. The activity of the type 2 inhibitor increased or decreased in opposite direction to changes of cerebellar cGMP content generated by injection of 10 mg/kg harmaline 2.5 mg diazepam. No changes of type 1 inhibitor were observed under these conditions. The drug-induced shift of type 2 inhibitor of protein kinase was not mediated by changes in protein synthesis because it persisted after pretreatment with cycloheximide. These results are compatible with the hypothesis that cGMP modulates phosphorylation in cerebellum by changing the relationship between cGMP-dependent protein kinase and type 2 inhibitor content.", "contents": "Action of harmaline and diazepam on the cerebellar content of cyclic GMP and on the activities of two endogenous inhibitors of protein kinase. The rat cerebellum contains a significant amount of cGMP-dependent protein kinase, cAMP-dependent and cyclic nucleotide-independent protein kinase, and a large concentration of protein kinase inhibitors. These inhibitors are thermostable proteins which can be separated by gel chromatography into two molecular forms: the type 1 and type 2 inhibitors of protein kinase (14). The type 1 inhibitor blocks the rat cerebellar cAMP-dependent protein kinase activity while the type 2 inhibitor blocks the cGMP-dependent protein kinase, the cAMP-dependent protein kinase, and the cyclic nucleotide-independent protein kinases. The activity of the type 2 inhibitor increased or decreased in opposite direction to changes of cerebellar cGMP content generated by injection of 10 mg/kg harmaline 2.5 mg diazepam. No changes of type 1 inhibitor were observed under these conditions. The drug-induced shift of type 2 inhibitor of protein kinase was not mediated by changes in protein synthesis because it persisted after pretreatment with cycloheximide. These results are compatible with the hypothesis that cGMP modulates phosphorylation in cerebellum by changing the relationship between cGMP-dependent protein kinase and type 2 inhibitor content."}
{"id": "PMID:223077", "title": "High-affinity uptake of gamma-aminobutyric acid in cultured glial and neuronal cells.", "content": "Both glial and neuronal cells maintained in primary culture were found to accumulate [3H]GABA by an efficient \"high-affinity\" uptake system (apparent Km = 9 muM, Vmax = 0.018 and 0.584 nmol/mg/min, respectively) which required sodium ions and was inhibited by 1 mM ouabain. Strychnine and parachloromercuriphenylsulfonate (pCS) (both at 1mM) also strongly inhibited uptake of [3H]GABA, but metabolic inhibitors (2,4-dinitrophenol, potassium cyanide, and malonate) were without effect. Only three structural analogs of GABA (nipecotate, beta-alanine, and 2,4-diaminobutyrate) inhibited uptake of [3H]GABA, while several other compounds with structural similarities to GABA (e.g. glycine, L-proline, and taurine) did not interact with the system. The kinetic studies indicated presence of a second uptake (Km = 92 muM, Vmax = 0.124 nmol/mg/min) in the primary cultures containing predominantly glioblasts. On the other hand, only one of the neuronal cell lines transformed by simian virus SV40 appeared to accumulate [3H]GABA against a concentration gradient. Apparent Km of this uptake was relatively high (819 muM), and it was only weakly inhibited by 1 mM ouabain and 1 mM pCS. The structural specificity also differed from that of the uptake observed in the primary cultures. Significantly, non of the nontransformed continuous cell lines of either tumoral (glioma, C6; neuroblastoma, M1; M1NN) or normal (NN;I6) origin actively accumulated [3H]GABA. It is suggested that for the neurochemical studies related to GABA and requiring homogeneous cell populations, the primary cultures offer a better experimental model than the continuous cell lines.", "contents": "High-affinity uptake of gamma-aminobutyric acid in cultured glial and neuronal cells. Both glial and neuronal cells maintained in primary culture were found to accumulate [3H]GABA by an efficient \"high-affinity\" uptake system (apparent Km = 9 muM, Vmax = 0.018 and 0.584 nmol/mg/min, respectively) which required sodium ions and was inhibited by 1 mM ouabain. Strychnine and parachloromercuriphenylsulfonate (pCS) (both at 1mM) also strongly inhibited uptake of [3H]GABA, but metabolic inhibitors (2,4-dinitrophenol, potassium cyanide, and malonate) were without effect. Only three structural analogs of GABA (nipecotate, beta-alanine, and 2,4-diaminobutyrate) inhibited uptake of [3H]GABA, while several other compounds with structural similarities to GABA (e.g. glycine, L-proline, and taurine) did not interact with the system. The kinetic studies indicated presence of a second uptake (Km = 92 muM, Vmax = 0.124 nmol/mg/min) in the primary cultures containing predominantly glioblasts. On the other hand, only one of the neuronal cell lines transformed by simian virus SV40 appeared to accumulate [3H]GABA against a concentration gradient. Apparent Km of this uptake was relatively high (819 muM), and it was only weakly inhibited by 1 mM ouabain and 1 mM pCS. The structural specificity also differed from that of the uptake observed in the primary cultures. Significantly, non of the nontransformed continuous cell lines of either tumoral (glioma, C6; neuroblastoma, M1; M1NN) or normal (NN;I6) origin actively accumulated [3H]GABA. It is suggested that for the neurochemical studies related to GABA and requiring homogeneous cell populations, the primary cultures offer a better experimental model than the continuous cell lines."}
{"id": "PMID:223079", "title": "Bovine dihydropteridine reductase: purification by affinity chromatography and comparison of enzymes from liver and adrenal medulla.", "content": "Dihydropteridine reductase has been purified to homogeneity from bovine liver and bovine adrenal medulla by precipitation with polyethylene glycol, ion exchange chromatography, gel filtration, and affinity chromatography on 5'-AMP-Sepharose 4B. The enzymes from the two tissues seem identical by the criteria of gel filtration chromatography, affinity chromatography, polyacrylamide gel electrophoresis in the presence and absence of dodecyl sulfate, isoelectric focusing, amino acid analysis, and binding of NADH. Fluorescence studies show two independent binding sites for NADH and a dissociation constant of 10 nM at pH 6.8. Isoelectric focusing of the enzyme as purified in the presence of NADH revealed three different bands, which by removal of this coenzyme were converted into a single band, corresponding to pI 5.7. The enzyme contains no carbohydrate or zinc.", "contents": "Bovine dihydropteridine reductase: purification by affinity chromatography and comparison of enzymes from liver and adrenal medulla. Dihydropteridine reductase has been purified to homogeneity from bovine liver and bovine adrenal medulla by precipitation with polyethylene glycol, ion exchange chromatography, gel filtration, and affinity chromatography on 5'-AMP-Sepharose 4B. The enzymes from the two tissues seem identical by the criteria of gel filtration chromatography, affinity chromatography, polyacrylamide gel electrophoresis in the presence and absence of dodecyl sulfate, isoelectric focusing, amino acid analysis, and binding of NADH. Fluorescence studies show two independent binding sites for NADH and a dissociation constant of 10 nM at pH 6.8. Isoelectric focusing of the enzyme as purified in the presence of NADH revealed three different bands, which by removal of this coenzyme were converted into a single band, corresponding to pI 5.7. The enzyme contains no carbohydrate or zinc."}
{"id": "PMID:223080", "title": "Distribution of opiate-like substances in rat tissues.", "content": "Rat tissues were tested for their ability to inhibit the binding of [3H]dihydromorphine or [3H]naloxone to membrane-bound opiate receptors. By this criterion, morphine-like substances were found in lung, heart, liver, and kidney as well as in brain. The relative activity of the extracts, based on initial tissue weight, differed with the radioactive lignand employed. With dihydromorphine, the order was as above. With naloxone, lung was most active, followed by heart, brain, liver, and kidney. The ability of all tissue extracts to inhibit opiate binding was reduced by 100 mM NaC1 and slightly reduced by 1 mM MnC1(2). Gel filtration using Sephadex G-25 indicated that the inhibitory substances were heterogeneous in molecular weight. Only with brain and kidney extracts was there significant activity at the elution volume where enkephalins would be expected. Fractionation using Amberlite XAD-2, a resin which selectively absorbs hydrophobic materials, again indicated that the major protion of activity in all tissue extracts was due to substances other than enkephalins.", "contents": "Distribution of opiate-like substances in rat tissues. Rat tissues were tested for their ability to inhibit the binding of [3H]dihydromorphine or [3H]naloxone to membrane-bound opiate receptors. By this criterion, morphine-like substances were found in lung, heart, liver, and kidney as well as in brain. The relative activity of the extracts, based on initial tissue weight, differed with the radioactive lignand employed. With dihydromorphine, the order was as above. With naloxone, lung was most active, followed by heart, brain, liver, and kidney. The ability of all tissue extracts to inhibit opiate binding was reduced by 100 mM NaC1 and slightly reduced by 1 mM MnC1(2). Gel filtration using Sephadex G-25 indicated that the inhibitory substances were heterogeneous in molecular weight. Only with brain and kidney extracts was there significant activity at the elution volume where enkephalins would be expected. Fractionation using Amberlite XAD-2, a resin which selectively absorbs hydrophobic materials, again indicated that the major protion of activity in all tissue extracts was due to substances other than enkephalins."}
{"id": "PMID:223082", "title": "Peripheral nerve injection injury: an experimental study.", "content": "In an attempt to answer questions regarding nerve injection injuries, we injected 11 agents in current use and commonly administered by intramuscular injection into the sciatic nerves of adult Wistar rats. Equal volumes of normal saline were used as control. We harvested the sciatic nerves at various times after injection and examined them by both light and electron microscopy. We performed myelinated nerve fiber counts and constructed histograms. Any impairment of motor function was also noted. We gave injections to 79 animals a total of 158 times; 116 injections were directly into the nerve fascicle (intrafascicular) and 42 were into the epineural tissue (extrafascicular). The results revealed considerable variation in the degree of nerve fiber injury according to the agent injected. Minimal damage resulted from the injection of iron-dextran, meperidine, and cephalothin, and maximal nerve injury followed the injection of penicillin, diazepam, and chlorpromazine. The site of injection was crucial. Intrafascicular injection was invariably associated with severe nerve injury, but, with few exceptions, extrafascicular injection resulted in minimal damage. The quantity of drug injected was also important in determining the degree of injury. Large, heavily myelinated fibers were more susceptible to injection injury than smaller, thinly myelinated nerve fibers. The effect of the injected drug seemed to be related to injury of the nerve fiber unit--both the axon and the Schwann cell with its myelin sheath. Regeneration in damaged nerves was a constant finding; even the most severely injured nerves, with total axonal degeneration, underwent subsequent regeneration.", "contents": "Peripheral nerve injection injury: an experimental study. In an attempt to answer questions regarding nerve injection injuries, we injected 11 agents in current use and commonly administered by intramuscular injection into the sciatic nerves of adult Wistar rats. Equal volumes of normal saline were used as control. We harvested the sciatic nerves at various times after injection and examined them by both light and electron microscopy. We performed myelinated nerve fiber counts and constructed histograms. Any impairment of motor function was also noted. We gave injections to 79 animals a total of 158 times; 116 injections were directly into the nerve fascicle (intrafascicular) and 42 were into the epineural tissue (extrafascicular). The results revealed considerable variation in the degree of nerve fiber injury according to the agent injected. Minimal damage resulted from the injection of iron-dextran, meperidine, and cephalothin, and maximal nerve injury followed the injection of penicillin, diazepam, and chlorpromazine. The site of injection was crucial. Intrafascicular injection was invariably associated with severe nerve injury, but, with few exceptions, extrafascicular injection resulted in minimal damage. The quantity of drug injected was also important in determining the degree of injury. Large, heavily myelinated fibers were more susceptible to injection injury than smaller, thinly myelinated nerve fibers. The effect of the injected drug seemed to be related to injury of the nerve fiber unit--both the axon and the Schwann cell with its myelin sheath. Regeneration in damaged nerves was a constant finding; even the most severely injured nerves, with total axonal degeneration, underwent subsequent regeneration."}
{"id": "PMID:223086", "title": "Suppression of foreign innervation in axolotl muscle may not be dependent on juxtaposition of native and foreign nerve terminals.", "content": "The posterior supracoracoideus nerve of the axolotl, Ambystoma mexicanum, was induced to make synapses outside its normal muscle territory. Muscle fibres with inputs from both native and foreign nerves were studied during the period of suppression of foreign transmission and in only 8% of fibres were foreign and native terminals found within 120 micrometer of each other. A combined cholinesterase/silver staining technique revealed non-innervated endplates in foreign-innervated fibres just prior to the return of the native nerve. These results suggest a mechanism enabling suppression of foreign synapses at some distance from native synapses probably beginning with the reinnervation of empty sites by the native nerve.", "contents": "Suppression of foreign innervation in axolotl muscle may not be dependent on juxtaposition of native and foreign nerve terminals. The posterior supracoracoideus nerve of the axolotl, Ambystoma mexicanum, was induced to make synapses outside its normal muscle territory. Muscle fibres with inputs from both native and foreign nerves were studied during the period of suppression of foreign transmission and in only 8% of fibres were foreign and native terminals found within 120 micrometer of each other. A combined cholinesterase/silver staining technique revealed non-innervated endplates in foreign-innervated fibres just prior to the return of the native nerve. These results suggest a mechanism enabling suppression of foreign synapses at some distance from native synapses probably beginning with the reinnervation of empty sites by the native nerve."}
{"id": "PMID:223087", "title": "The effects of intranigral injections of picrotoxin and carbachol in cats with a lesioned nigrostriatal pathway.", "content": "Picrotoxin, carbachol and atropine were injected intranigrally through chronically implanted crannulae in cats. The drug-induced behavioural syndromes, mainly asymmetric behaviour, were analyzed. The changes in these syndromes after 6-hydroxydopamine (6-OHDA) lesion of the substantia nigra (SN) indicate that, in addition to the dopaminergic (DA), a non-catecholaminergic (non-CA) nigral output exists, both being responsible for asymmetric behaviour. It is further suggested that gamma-aminobutyric acid (GABA) receptors are present on both dopaminergic and non-CA nigral output neurons, while acetylcholine (ACh) receptors, responsible for asymmetric behaviour, are almost exclusively located on non-CA nigral output neurons.", "contents": "The effects of intranigral injections of picrotoxin and carbachol in cats with a lesioned nigrostriatal pathway. Picrotoxin, carbachol and atropine were injected intranigrally through chronically implanted crannulae in cats. The drug-induced behavioural syndromes, mainly asymmetric behaviour, were analyzed. The changes in these syndromes after 6-hydroxydopamine (6-OHDA) lesion of the substantia nigra (SN) indicate that, in addition to the dopaminergic (DA), a non-catecholaminergic (non-CA) nigral output exists, both being responsible for asymmetric behaviour. It is further suggested that gamma-aminobutyric acid (GABA) receptors are present on both dopaminergic and non-CA nigral output neurons, while acetylcholine (ACh) receptors, responsible for asymmetric behaviour, are almost exclusively located on non-CA nigral output neurons."}
{"id": "PMID:223088", "title": "Ability of calf brain synaptic membranes to bind [35S]taurine to their triton X-100 and chloroform extracts.", "content": "A protein fraction containing reducing sugars was prepared from calf brain synaptic membranes with 0.5% Triton X-100, and another fraction containing bound phosphorus with a 2 : 1 chloroform--methanol mixture. Both protein fractions bound small amounts of [35S]taurine, the first fraction about 25 pmol/g protein and the second about 220 pmol/g protein. The Triton X-100 extract represented 13.8% of the membrane proteins, but the chloroform--methanol extract only 0.9%. The binding of taurine to the Trition X-100 extract was temperature sensitive, but was only slightly inhibited by hypotaurine and beta-alanine.", "contents": "Ability of calf brain synaptic membranes to bind [35S]taurine to their triton X-100 and chloroform extracts. A protein fraction containing reducing sugars was prepared from calf brain synaptic membranes with 0.5% Triton X-100, and another fraction containing bound phosphorus with a 2 : 1 chloroform--methanol mixture. Both protein fractions bound small amounts of [35S]taurine, the first fraction about 25 pmol/g protein and the second about 220 pmol/g protein. The Triton X-100 extract represented 13.8% of the membrane proteins, but the chloroform--methanol extract only 0.9%. The binding of taurine to the Trition X-100 extract was temperature sensitive, but was only slightly inhibited by hypotaurine and beta-alanine."}
{"id": "PMID:223090", "title": "Localization of opiate receptors in substantia nigra evidence by lesion studies.", "content": "From the effects of selective lesions it is concluded that opiate receptors are located on dopamine (DA) cell-bodies and/or dendrites as well as on GABA nerve-terminals in substantia nigra.", "contents": "Localization of opiate receptors in substantia nigra evidence by lesion studies. From the effects of selective lesions it is concluded that opiate receptors are located on dopamine (DA) cell-bodies and/or dendrites as well as on GABA nerve-terminals in substantia nigra."}
{"id": "PMID:223091", "title": "A study on the effects of interaction between naloxone and 2-Br-alpha-ergocryptine or clonidine on luteinizing hormone, follicle-stimulating hormone, prolactin and thyroid-stimulating hormone levels in normal man serum.", "content": "The effects of 2-Br-alpha-ergocryptine (2.5 mg/osM), clonidine (50 microgram, intramuscularly) and naloxone (0.4 mg, intramuscularly) as well as the interaction between naloxone and 2-Br-alpha-ergocryptine or clonidine on luteinizing hormone (LH) follicle-stimulating hormone (FSH), prolactin (PL) and thyroid-stimulating hormone (TSH) serum levels in normal man have been studied. 2-Br-alpha-ergocryptine and clonidine clearly reduce and naloxone tends to reduce PL serum levels. TSH levels are lowered by naloxone as well by clonidine plus naloxone. The results obtained point also to a possible different pattern of LH and FSH secretion after naloxone, that is after opiate receptor blockade. The clonidine effects on PL secretion are discussed in the frame of a possible adrenergic control of the release of this hormone.", "contents": "A study on the effects of interaction between naloxone and 2-Br-alpha-ergocryptine or clonidine on luteinizing hormone, follicle-stimulating hormone, prolactin and thyroid-stimulating hormone levels in normal man serum. The effects of 2-Br-alpha-ergocryptine (2.5 mg/osM), clonidine (50 microgram, intramuscularly) and naloxone (0.4 mg, intramuscularly) as well as the interaction between naloxone and 2-Br-alpha-ergocryptine or clonidine on luteinizing hormone (LH) follicle-stimulating hormone (FSH), prolactin (PL) and thyroid-stimulating hormone (TSH) serum levels in normal man have been studied. 2-Br-alpha-ergocryptine and clonidine clearly reduce and naloxone tends to reduce PL serum levels. TSH levels are lowered by naloxone as well by clonidine plus naloxone. The results obtained point also to a possible different pattern of LH and FSH secretion after naloxone, that is after opiate receptor blockade. The clonidine effects on PL secretion are discussed in the frame of a possible adrenergic control of the release of this hormone."}
{"id": "PMID:223092", "title": "Prostaglandin E1 raises the cAMP content of peripheral nerve tissue.", "content": "Prostaglandins of the E type have been found to increase the cAMP content in peripheral nerve tissue of several species. In rabbit vagus nerve, for example, the effect is rapid (1--5 min), it can be elicited by 10(-6) M PGE1 and it is maximal at 10(-5) M. In this preparation the increase of the cAMP content caused by PGE1 is about 4-fold, whereas it is about 2-fold in the vagus of calf. PGE1 also causes an increase in cAMP level in the superior cervical ganglion of calf, rat and rabbit. In these tissues, however, the presence of a phosphodiesterase inhibitor is required for cAMP accumulation.", "contents": "Prostaglandin E1 raises the cAMP content of peripheral nerve tissue. Prostaglandins of the E type have been found to increase the cAMP content in peripheral nerve tissue of several species. In rabbit vagus nerve, for example, the effect is rapid (1--5 min), it can be elicited by 10(-6) M PGE1 and it is maximal at 10(-5) M. In this preparation the increase of the cAMP content caused by PGE1 is about 4-fold, whereas it is about 2-fold in the vagus of calf. PGE1 also causes an increase in cAMP level in the superior cervical ganglion of calf, rat and rabbit. In these tissues, however, the presence of a phosphodiesterase inhibitor is required for cAMP accumulation."}
{"id": "PMID:223095", "title": "Persistence of virus shedding in asymptomatic women after recovery from herpes genitalis.", "content": "One hundred seventeen women were reexamined within 6 months after presenting with genital herpes. Swabs for virus isolation were taken from the cervix whether or not lesions were observed. Herpesvirus type II was isolated from 30 of 67 patients with recurrent disease, but also from 5 of 50 women during periods when there were no signs or symptoms of illness. The epidemiologic importance of virus shedding from asymptomatic women is discussed.", "contents": "Persistence of virus shedding in asymptomatic women after recovery from herpes genitalis. One hundred seventeen women were reexamined within 6 months after presenting with genital herpes. Swabs for virus isolation were taken from the cervix whether or not lesions were observed. Herpesvirus type II was isolated from 30 of 67 patients with recurrent disease, but also from 5 of 50 women during periods when there were no signs or symptoms of illness. The epidemiologic importance of virus shedding from asymptomatic women is discussed."}
{"id": "PMID:223098", "title": "Herpes virus infection as a cofactor in carcinogenesis: supernatants of herpes virus type 1- and type 2-infected cell cultures contain a cell growth-stimulating factor.", "content": "Some cell cultures synthesize a mitogenic factor (DNASF) following their lytic infection with either HSV-1 or HSV-2 which is shed into the medium. Of six cell lines permissive to HSV infection tested, three produce DNASF (CV1, HF, MCA) and a significantly higher (3H)-TdR incorporation was obtained with indicator cells growing in supernatants of virus-infected cells (SupV+) than in the corresponding supernatants of sham-treated cells (SupV-). Sometimes the values obtained with SupV+ exceed those obtained with cell controls, which demonstrates that DNASF is not simply a nutritional factor. Other cell lines do not produce DNASF (HeLa, Wistar and probably REF) and SupV+ frequently inhibit cell growth. DNASF is genetically nonspecific and all indicator cells tested were stimulated by supernatants which contain the mitogen, including the nonpermissive DC-3F cells. The quantity of DNASF induced is directly proportional to the number of cells in the culture and its production peaks when the lysis of the cells is complete. It is not accumulated inside the cells.", "contents": "Herpes virus infection as a cofactor in carcinogenesis: supernatants of herpes virus type 1- and type 2-infected cell cultures contain a cell growth-stimulating factor. Some cell cultures synthesize a mitogenic factor (DNASF) following their lytic infection with either HSV-1 or HSV-2 which is shed into the medium. Of six cell lines permissive to HSV infection tested, three produce DNASF (CV1, HF, MCA) and a significantly higher (3H)-TdR incorporation was obtained with indicator cells growing in supernatants of virus-infected cells (SupV+) than in the corresponding supernatants of sham-treated cells (SupV-). Sometimes the values obtained with SupV+ exceed those obtained with cell controls, which demonstrates that DNASF is not simply a nutritional factor. Other cell lines do not produce DNASF (HeLa, Wistar and probably REF) and SupV+ frequently inhibit cell growth. DNASF is genetically nonspecific and all indicator cells tested were stimulated by supernatants which contain the mitogen, including the nonpermissive DC-3F cells. The quantity of DNASF induced is directly proportional to the number of cells in the culture and its production peaks when the lysis of the cells is complete. It is not accumulated inside the cells."}
{"id": "PMID:223100", "title": "[Catecholamine sensitivity of the hypophyseal-adrenal system in the early ontogeny of rats].", "content": "The dynamics of the hypophyseal-suprarenal system reaction to catecholamines of different type of effect was studied in the Wistar rats during the first 16 days of life. The reaction to epinephrine was noted in 4 days old and to novodrin in 8 days old rats. Since the reaction to epinephrine acting on alpha- and beta-receptors appears ahead of that to novodrin acting selectively on beta-receptors, a suggestion was put forward to the effect that alpha-receptors matured more rapidly that beta-receptors. The increase of the system reaction to the stimulation of recepors sensitive to catecholamines was noted on the 12-14th days of life and appears to be related to the formation of central adrenergic mechanisms.", "contents": "[Catecholamine sensitivity of the hypophyseal-adrenal system in the early ontogeny of rats]. The dynamics of the hypophyseal-suprarenal system reaction to catecholamines of different type of effect was studied in the Wistar rats during the first 16 days of life. The reaction to epinephrine was noted in 4 days old and to novodrin in 8 days old rats. Since the reaction to epinephrine acting on alpha- and beta-receptors appears ahead of that to novodrin acting selectively on beta-receptors, a suggestion was put forward to the effect that alpha-receptors matured more rapidly that beta-receptors. The increase of the system reaction to the stimulation of recepors sensitive to catecholamines was noted on the 12-14th days of life and appears to be related to the formation of central adrenergic mechanisms."}
{"id": "PMID:223101", "title": "A testicular tumor with gingival metastasis.", "content": "Testicular tumors comprise approximately 1 percent of all malignant neoplasms in the male. However, they are one of the more common malignant diseases of adolescent and young adult males. An unusual case of a testicular neoplasm in a 23-year-old man exhibiting gingival metastasis is presented.", "contents": "A testicular tumor with gingival metastasis. Testicular tumors comprise approximately 1 percent of all malignant neoplasms in the male. However, they are one of the more common malignant diseases of adolescent and young adult males. An unusual case of a testicular neoplasm in a 23-year-old man exhibiting gingival metastasis is presented."}
{"id": "PMID:223105", "title": "Inhibition of the spinal transmission of nociceptive information by supraspinal stimulation in the cat.", "content": "In cats anaesthetized with alpha-chloralose or sodium pentobarbitone a study was made of the effects of supraspinal electrical stimulation on the excitation of dorsal horn neurones by noxious and non-noxious cutaneous stimuli. Stimulation near the dorsal raphe of the midbrain non-selectively reduced the responses of neurones to both noxious and non-noxious stimuli. Intravenous naloxone (0.3-0.6 mg/kg) had no effect on this inhibition. Electrical stimulation near the medullary raphe selectively reduced the excitation of dorsal horn neurones by noxious cutaneous stimuli. Excitation of neurones by deflection of hairs was unaffected. The inhibition of nociceptive responses outlasted the period of raphe stimulation by up to 6 min. Intravenous naloxone (0.6-1.0 mg/kg) also failed to affect this selective inhibition.", "contents": "Inhibition of the spinal transmission of nociceptive information by supraspinal stimulation in the cat. In cats anaesthetized with alpha-chloralose or sodium pentobarbitone a study was made of the effects of supraspinal electrical stimulation on the excitation of dorsal horn neurones by noxious and non-noxious cutaneous stimuli. Stimulation near the dorsal raphe of the midbrain non-selectively reduced the responses of neurones to both noxious and non-noxious stimuli. Intravenous naloxone (0.3-0.6 mg/kg) had no effect on this inhibition. Electrical stimulation near the medullary raphe selectively reduced the excitation of dorsal horn neurones by noxious cutaneous stimuli. Excitation of neurones by deflection of hairs was unaffected. The inhibition of nociceptive responses outlasted the period of raphe stimulation by up to 6 min. Intravenous naloxone (0.6-1.0 mg/kg) also failed to affect this selective inhibition."}
{"id": "PMID:223119", "title": "[Tumoural calcinosis in a white male (author's transl)].", "content": "A case of tumoural calcinosis in a 61-years-old man. This is a rare condition (60 published cases), affecting above all black subjects. It takes the form of hard rounded masses which progressively increase in size and vary in their location (hips, elbows, shoulders, periscapular region). On X-rays, the tumour is rounded, consisting of a mass of several calcified small nodules. On technetium pyrophosphate isotope scanning, there is very marked and periarticular uptake. There is often hyperphosphoraemia associated with normal blood calcium levels, without any abnormality in the hormones controlling calcium and phosphate metabolism. Treatment usually consists of the excision of the tumour masses. More recently, the reduction of hyperphosphoraemia by the prescription of aluminium salts and a reduction in phosphorus intake has been suggested.", "contents": "[Tumoural calcinosis in a white male (author's transl)]. A case of tumoural calcinosis in a 61-years-old man. This is a rare condition (60 published cases), affecting above all black subjects. It takes the form of hard rounded masses which progressively increase in size and vary in their location (hips, elbows, shoulders, periscapular region). On X-rays, the tumour is rounded, consisting of a mass of several calcified small nodules. On technetium pyrophosphate isotope scanning, there is very marked and periarticular uptake. There is often hyperphosphoraemia associated with normal blood calcium levels, without any abnormality in the hormones controlling calcium and phosphate metabolism. Treatment usually consists of the excision of the tumour masses. More recently, the reduction of hyperphosphoraemia by the prescription of aluminium salts and a reduction in phosphorus intake has been suggested."}
{"id": "PMID:223121", "title": "[Acute pancreatitis during \"diabetic lipemia\": unusual disclosure of insulin-dependent diabetes (author's transl)].", "content": "A case of diabetic lipemia is reported in a 27 year-old man admitted for acute pancreatitis. Initial investigations revealed gross hyperlipoproteinemia and ketoacidosis. Hyperlipoproteinemia was progressively corrected up to normalization in four weeks under insulin-therapy; the metabolic control of diabetes was obtained in parellel. This feature is caracteristic of \"diabetic lipemia\". The following sequence could be suggested: onset of diabetes, occurence of diabetic lipemia and then acute pancreatitis.", "contents": "[Acute pancreatitis during \"diabetic lipemia\": unusual disclosure of insulin-dependent diabetes (author's transl)]. A case of diabetic lipemia is reported in a 27 year-old man admitted for acute pancreatitis. Initial investigations revealed gross hyperlipoproteinemia and ketoacidosis. Hyperlipoproteinemia was progressively corrected up to normalization in four weeks under insulin-therapy; the metabolic control of diabetes was obtained in parellel. This feature is caracteristic of \"diabetic lipemia\". The following sequence could be suggested: onset of diabetes, occurence of diabetic lipemia and then acute pancreatitis."}
{"id": "PMID:223123", "title": "[The treatment of advanced malignant melanoma with vaccina oncolysates (author's transl)].", "content": "Ten patients with recurrent stage II or III malignant melanoma received a live vaccinia virus augmented malignant melanoma cell vaccine. No patient had adverse reactions. The 3 patients surviving (10, 18 and 19 months) had: positive skin reactions to the vaccine (as they had previous positive skin reactions to common recall antigens), elevated vaccinia antibody titers, and they showed lack of progression of the disease with immunotherapy.", "contents": "[The treatment of advanced malignant melanoma with vaccina oncolysates (author's transl)]. Ten patients with recurrent stage II or III malignant melanoma received a live vaccinia virus augmented malignant melanoma cell vaccine. No patient had adverse reactions. The 3 patients surviving (10, 18 and 19 months) had: positive skin reactions to the vaccine (as they had previous positive skin reactions to common recall antigens), elevated vaccinia antibody titers, and they showed lack of progression of the disease with immunotherapy."}
{"id": "PMID:223124", "title": "[Water and electrolytes intestinal secretion (author's transl)].", "content": "This paper reviews methods used for studying intestinal secretion in man and animals, fasting and post prandial intestinal secretion, as well as that induced by bacterial enterotoxins, hormonal stimuli, some endocrine tumours and various intraluminary agents; finally the possible mechanisms and sites of intestinal secretion are discussed. That the intestine secretes fluid under physiological conditions is not proven but seems very likely. Several mechanisms seem to be involved in the production of fluid by the intestine. The adenylate-cyclase-cyclic adenosine monophosphate (AMPc) system is currently thought to play a major role in endotoxins and some hormone-induced secretions. The site of intestinal secretion remains a matter of discussion: both crypts and villi seem to participate in the secretory process.", "contents": "[Water and electrolytes intestinal secretion (author's transl)]. This paper reviews methods used for studying intestinal secretion in man and animals, fasting and post prandial intestinal secretion, as well as that induced by bacterial enterotoxins, hormonal stimuli, some endocrine tumours and various intraluminary agents; finally the possible mechanisms and sites of intestinal secretion are discussed. That the intestine secretes fluid under physiological conditions is not proven but seems very likely. Several mechanisms seem to be involved in the production of fluid by the intestine. The adenylate-cyclase-cyclic adenosine monophosphate (AMPc) system is currently thought to play a major role in endotoxins and some hormone-induced secretions. The site of intestinal secretion remains a matter of discussion: both crypts and villi seem to participate in the secretory process."}
{"id": "PMID:223125", "title": "Direct detection of methylated cytosine in DNA by use of the restriction enzyme MspI.", "content": "The extent of methylation of the internal C in the sequence CCGG in DNA from various eukaryotic sources has been determined using the restriction enzyme MspI known to be specific for this sequence. The methylation of the CCGG sequence is reflected in the restriction pattern obtained by DNA treated with MspI and its isoschizomer HpaII and analyzed by gel electrophoresis. A direct method for detection 5-methylcytosine in the sequence CCGG has been deviced. DNA fragments obtained with MspI were radioactively labeled at their 5' ends and subsequently degraded to the corresponding 5'-deoxyribonucleoside monophosphates. 5 methylcytidylic acid has been found in most of the 5' ends of MspI fragments of calf thymus DNA (about 90%) indicating heavy methylation of the sequence CCGG in calf thymus DNA. The results also reveal a symmetric methylation of both strands at this sequence in calf thymus DNA. In contrast, the CCGG sequence in other eukaryotic DNAs from organisms like Neurospora, Drosophila and Herpes virus proved to be undermethylated at this sequence.", "contents": "Direct detection of methylated cytosine in DNA by use of the restriction enzyme MspI. The extent of methylation of the internal C in the sequence CCGG in DNA from various eukaryotic sources has been determined using the restriction enzyme MspI known to be specific for this sequence. The methylation of the CCGG sequence is reflected in the restriction pattern obtained by DNA treated with MspI and its isoschizomer HpaII and analyzed by gel electrophoresis. A direct method for detection 5-methylcytosine in the sequence CCGG has been deviced. DNA fragments obtained with MspI were radioactively labeled at their 5' ends and subsequently degraded to the corresponding 5'-deoxyribonucleoside monophosphates. 5 methylcytidylic acid has been found in most of the 5' ends of MspI fragments of calf thymus DNA (about 90%) indicating heavy methylation of the sequence CCGG in calf thymus DNA. The results also reveal a symmetric methylation of both strands at this sequence in calf thymus DNA. In contrast, the CCGG sequence in other eukaryotic DNAs from organisms like Neurospora, Drosophila and Herpes virus proved to be undermethylated at this sequence."}
{"id": "PMID:223126", "title": "Isolation and characterization of rabbit anti-m7G-5'-P antibodies of high apparent affinity.", "content": "Antibodies highly specific for intact pm7G (7methylguanosine-5'-mono-phosphate) were induced by immunization of rabbits with a pm7G-BSA conjugate. Since the nucleotide is six-fold more stable than m7G (7-methylguanosine) to alkali-catalyzed fission of the imidazole ring, it is a more desirable antigen for obtaining antibodies capable of binding caps on eukaryotic mRNA. UV spectra demonstrated that the nucleotide in the conjugate was predominantly the intact form. Competition radioimmunoassay showed 1) high apparent affinities for pm7G, on the order of 10(-8)M, 2) low competition by the ring-opened form of the homologous hapten (*pm7G), and by m7G, 3) little or no competition by AMP, GMP, CMP, UMP or m6A, and 4) high apparent affinities for m7GpppAm, m7GpppN6MAm, m7GpppGm, m7GpppA.", "contents": "Isolation and characterization of rabbit anti-m7G-5'-P antibodies of high apparent affinity. Antibodies highly specific for intact pm7G (7methylguanosine-5'-mono-phosphate) were induced by immunization of rabbits with a pm7G-BSA conjugate. Since the nucleotide is six-fold more stable than m7G (7-methylguanosine) to alkali-catalyzed fission of the imidazole ring, it is a more desirable antigen for obtaining antibodies capable of binding caps on eukaryotic mRNA. UV spectra demonstrated that the nucleotide in the conjugate was predominantly the intact form. Competition radioimmunoassay showed 1) high apparent affinities for pm7G, on the order of 10(-8)M, 2) low competition by the ring-opened form of the homologous hapten (*pm7G), and by m7G, 3) little or no competition by AMP, GMP, CMP, UMP or m6A, and 4) high apparent affinities for m7GpppAm, m7GpppN6MAm, m7GpppGm, m7GpppA."}
{"id": "PMID:223127", "title": "Fluoride ion catalyzed alkylation of nucleic acid derivatives using trialkyl phosphates, dialkyl sulfates and alkyl methanesulfonates.", "content": "Trimethyl phosphate, dimethyl and diethyl sulfate and methyl and ethyl methanesulfonate all give high yields of alkylation on purines and pyrimidines in the presence of tetrabutylammonium fluoride. Trimethyl phosphate produces near quantitative yields of diesters of nucleic acids but gives virtually no triester formation. The alkyl sulfates produce very high yields of triesters of nucleic acids including cyclic phosphates while the alkyl methanesulfonates are intermediate in reactivity. It was observed that in the absence of fluoride ion the dialkylsulfates gave reasonable yields of thymidine monosulfates.", "contents": "Fluoride ion catalyzed alkylation of nucleic acid derivatives using trialkyl phosphates, dialkyl sulfates and alkyl methanesulfonates. Trimethyl phosphate, dimethyl and diethyl sulfate and methyl and ethyl methanesulfonate all give high yields of alkylation on purines and pyrimidines in the presence of tetrabutylammonium fluoride. Trimethyl phosphate produces near quantitative yields of diesters of nucleic acids but gives virtually no triester formation. The alkyl sulfates produce very high yields of triesters of nucleic acids including cyclic phosphates while the alkyl methanesulfonates are intermediate in reactivity. It was observed that in the absence of fluoride ion the dialkylsulfates gave reasonable yields of thymidine monosulfates."}
{"id": "PMID:223128", "title": "Sequence and location of the poly C tract in aphtho- and cardiovirus RNA.", "content": "The poly C tract in the RNA of the aphtho- and cardio viruses has been examined in several isolates of foot-and-mouth disease virus (FMDV) and encephalomyocarditis (EMC) virus. The length of the tract is variable, containing 100 to 170 bases in the FMDV isolates and 80 to 250 bases in the EMC virus isolates. Each poly C tract contains c. 10% A and U residues, located at the 5' end, i.e. most of the tract is a continuous run of C residues. The position of the tract on the genome was the same in each of the FMDV isolates, about 400 bases from the 5' end, whereas in the EMC virus isolates it was about 150 bases from the 5' end.", "contents": "Sequence and location of the poly C tract in aphtho- and cardiovirus RNA. The poly C tract in the RNA of the aphtho- and cardio viruses has been examined in several isolates of foot-and-mouth disease virus (FMDV) and encephalomyocarditis (EMC) virus. The length of the tract is variable, containing 100 to 170 bases in the FMDV isolates and 80 to 250 bases in the EMC virus isolates. Each poly C tract contains c. 10% A and U residues, located at the 5' end, i.e. most of the tract is a continuous run of C residues. The position of the tract on the genome was the same in each of the FMDV isolates, about 400 bases from the 5' end, whereas in the EMC virus isolates it was about 150 bases from the 5' end."}
{"id": "PMID:223129", "title": "Evidence for removal at different rates of O-ethyl pyrimidines and ethylphosphotriesters in two human fibroblast cell lines.", "content": "The potent carcinogen, ethylnitrosourea, has been shown to ethylate oxygens, in preference to nitrogens, in the DNA of cultured cells. We have now studied the removal of seven ethyl derivatives in replicating cells. The following findings are reported. 1) The absolute amounts of 02-EtT, 04-EtT and 02-EtC are decreased in cellular DNA after correction for cell growth. However the rate of decrease diminishes after approximately 20 hr and after more than two cell doublings 20--40% of each derivative persists. This decrease is presumed to be due to enzymes since these derivatives are stable in isolated DNA. 2) The amount of ethyl phosphotriesters remains almost unchanged during 72 hr of cell culture. 3) The unstable purine derivatives, 7-EtG and 3-EtA, are both removed from cellular DNA with a rate faster than can be accounted for by the lability of the glycosyl bond. 4) Both GM 637 fibroblasts and Xeroderma pigmentosum fibroblasts (12-RO) (XP-12) have similar ability to remove ethyl products, except for O6-ethyl G which persists to a greater extent in XP12 cells. 5) The implications of the in vivo persistence of ethylated bases is discussed in regard to recent demonstrations that O2-EtT, O4-ET, O2-EtC and O6-EtG are all mutagenic.", "contents": "Evidence for removal at different rates of O-ethyl pyrimidines and ethylphosphotriesters in two human fibroblast cell lines. The potent carcinogen, ethylnitrosourea, has been shown to ethylate oxygens, in preference to nitrogens, in the DNA of cultured cells. We have now studied the removal of seven ethyl derivatives in replicating cells. The following findings are reported. 1) The absolute amounts of 02-EtT, 04-EtT and 02-EtC are decreased in cellular DNA after correction for cell growth. However the rate of decrease diminishes after approximately 20 hr and after more than two cell doublings 20--40% of each derivative persists. This decrease is presumed to be due to enzymes since these derivatives are stable in isolated DNA. 2) The amount of ethyl phosphotriesters remains almost unchanged during 72 hr of cell culture. 3) The unstable purine derivatives, 7-EtG and 3-EtA, are both removed from cellular DNA with a rate faster than can be accounted for by the lability of the glycosyl bond. 4) Both GM 637 fibroblasts and Xeroderma pigmentosum fibroblasts (12-RO) (XP-12) have similar ability to remove ethyl products, except for O6-ethyl G which persists to a greater extent in XP12 cells. 5) The implications of the in vivo persistence of ethylated bases is discussed in regard to recent demonstrations that O2-EtT, O4-ET, O2-EtC and O6-EtG are all mutagenic."}
{"id": "PMID:223130", "title": "Identification and mapping of N6-methyladenosine containing sequences in simian virus 40 RNA.", "content": "Late SV40 16S and 19S mRNAs were found to contain an average of three m6A residues per mRNA molecule. The methylated residues of both the viral and cellular mRNAs occur in two sequences; Gpm6ApC and (Ap)nm6ApC, where n = 1-4. More than 60% of the m6A residues in SV40 16S and 19S mRNAs occur in Gpm6ApC even though there are twice as many (A)nAC than GAC sequences in these messengers. The m6A containing oligonucleotides of late SV40 MRNAs were localized in the viral messengers. In the 16S mRNA two m6A oligonucleotides were located at the 5' coding region between 0.95--0.0 map units. The third m6A residue was mapped between 0.0--0.14 map units in the translated portion of this mRNA. The overall pattern of internal methylation in the 19S mRNA is similar. However, some differences between 16S and 19S mRNAs were observed in both the content and location of the longer (Ap)n m6AC nucleotides. These results provide the first example of precise localization of internal methylation sequences in mRNA species with defined coding specificity. It implies that a) location of m6A residues is not random but specific to a particular region of the RNA, b) apart from sequence specificity other structural features of the mRNA may influence internal methylation and c) m6A residues are present in coding regions of SV40 mRNAs.", "contents": "Identification and mapping of N6-methyladenosine containing sequences in simian virus 40 RNA. Late SV40 16S and 19S mRNAs were found to contain an average of three m6A residues per mRNA molecule. The methylated residues of both the viral and cellular mRNAs occur in two sequences; Gpm6ApC and (Ap)nm6ApC, where n = 1-4. More than 60% of the m6A residues in SV40 16S and 19S mRNAs occur in Gpm6ApC even though there are twice as many (A)nAC than GAC sequences in these messengers. The m6A containing oligonucleotides of late SV40 MRNAs were localized in the viral messengers. In the 16S mRNA two m6A oligonucleotides were located at the 5' coding region between 0.95--0.0 map units. The third m6A residue was mapped between 0.0--0.14 map units in the translated portion of this mRNA. The overall pattern of internal methylation in the 19S mRNA is similar. However, some differences between 16S and 19S mRNAs were observed in both the content and location of the longer (Ap)n m6AC nucleotides. These results provide the first example of precise localization of internal methylation sequences in mRNA species with defined coding specificity. It implies that a) location of m6A residues is not random but specific to a particular region of the RNA, b) apart from sequence specificity other structural features of the mRNA may influence internal methylation and c) m6A residues are present in coding regions of SV40 mRNAs."}
{"id": "PMID:223131", "title": "Transcription of nucleosomal DNA in SV40 minichromosomes by eukaryotic and prokaryotic RNA polymerases.", "content": "SV 40 minichromosomes can be transcribed by prokaryotic and eukaryotic RNA polymerases. Size analysis of transcripts indicated that DNA in nucleosomes was accessible for transcription by both enzymes. Sedimentation of the transcription complex showed that minichromosomes which were being transcribed had a full complement of nucleosomes. Strand selection by E. coli RNA polymerase was reduced by the presence of nucleosomes. No region of SV 40 DNA was preferentially transcribed on minichromosomes by either enzyme.", "contents": "Transcription of nucleosomal DNA in SV40 minichromosomes by eukaryotic and prokaryotic RNA polymerases. SV 40 minichromosomes can be transcribed by prokaryotic and eukaryotic RNA polymerases. Size analysis of transcripts indicated that DNA in nucleosomes was accessible for transcription by both enzymes. Sedimentation of the transcription complex showed that minichromosomes which were being transcribed had a full complement of nucleosomes. Strand selection by E. coli RNA polymerase was reduced by the presence of nucleosomes. No region of SV 40 DNA was preferentially transcribed on minichromosomes by either enzyme."}
{"id": "PMID:223132", "title": "Unusual silica granulomas of the skin with massive involvement of axillary lymph nodes.", "content": "Silica granulomas are rare in the skin. Involvement of the regional lymph nodes seems to be unusual. The case of a 35-year-old man with massive diffuse fibrosis of the axilla with multiple foreign body granulomas and involvement of axillary lymph nodes is presented. The lymph nodes exhibit multiple epithelioid cell granulomas and silicotic nodules which are indistinguishable from similar nodules in mediastinal lymph nodes in pulmonary silicosis. It is assumed that the numerous silica particles which were identified by X-ray microanalysis under the scanning electron microscope and recovered from the mineral ash after incineration were accidentally implanted into the skin at the time of an injury 26 years previously. The long delay between silica exposure and granuloma development is a typical feature of these lesions. The possible mechanisms operative in this process are discussed.", "contents": "Unusual silica granulomas of the skin with massive involvement of axillary lymph nodes. Silica granulomas are rare in the skin. Involvement of the regional lymph nodes seems to be unusual. The case of a 35-year-old man with massive diffuse fibrosis of the axilla with multiple foreign body granulomas and involvement of axillary lymph nodes is presented. The lymph nodes exhibit multiple epithelioid cell granulomas and silicotic nodules which are indistinguishable from similar nodules in mediastinal lymph nodes in pulmonary silicosis. It is assumed that the numerous silica particles which were identified by X-ray microanalysis under the scanning electron microscope and recovered from the mineral ash after incineration were accidentally implanted into the skin at the time of an injury 26 years previously. The long delay between silica exposure and granuloma development is a typical feature of these lesions. The possible mechanisms operative in this process are discussed."}
{"id": "PMID:223133", "title": "Myelolipoma in adenoma of accessory adrenal gland.", "content": "A tumor was incidentally found at autopsy in the vicinity of the right adrenal gland of a 69-year-old man who had died of liver cirrhosis with hepatoma. Microscopic examination disclosed a myelolipoma associated with a cortical adenoma occurring in an accessory adrenal gland. No evidence of hormonal abnormalities was found in the clinical record of the patient. The association of myelolipoma with cortical adenoma occurring in an accessory adrenal gland seems very unusual, and the present case is believed to be the first reported of this type of association.", "contents": "Myelolipoma in adenoma of accessory adrenal gland. A tumor was incidentally found at autopsy in the vicinity of the right adrenal gland of a 69-year-old man who had died of liver cirrhosis with hepatoma. Microscopic examination disclosed a myelolipoma associated with a cortical adenoma occurring in an accessory adrenal gland. No evidence of hormonal abnormalities was found in the clinical record of the patient. The association of myelolipoma with cortical adenoma occurring in an accessory adrenal gland seems very unusual, and the present case is believed to be the first reported of this type of association."}
{"id": "PMID:223134", "title": "A mode of incipient growth in chemically induced signet ring cell carcinoma of the canine stomach.", "content": "A 31-month-old female mongrel dog was orally administered with 50 mg or 100 mg of N-nitrosobutylurea (NBU) in gelatin-capsule 3 times per week for 19 months with interposing periods of complete suspension. Thirty-four foci of signet ring cell carcinoma were found in the antral region of the stomach. The majority of the foci (31 foci) were early cancer, and the remaining foci were invasive cancer. In addition to these lesions, there was \"a single gland cancer\" in which a row of cancer cells was confined to a single gland. The whole gland was composed of two cell layers; the inner layer facing the lumen was normal gastric cells and the outer layer was atypical or neoplastic cells underlaid by the basement membrane. Mitosis was frequently observed on the bottom of the gland. Atypical or neoplastic cells seemed to mature gradually through a process of upward migration with increase in cytoplasmic Alcian blue-PAS and HID-AB positive mucin. Some of the cells rich in mucin moved into the lamina propria. The other cells remained in the flow of the regular cell renewal system of the normal gastric cells and reached the top of the gland. This observation revealed a mode of incipient gastric cancer growth, which starts and spreads within a single gland, before it invades the surrounding lamina propria.", "contents": "A mode of incipient growth in chemically induced signet ring cell carcinoma of the canine stomach. A 31-month-old female mongrel dog was orally administered with 50 mg or 100 mg of N-nitrosobutylurea (NBU) in gelatin-capsule 3 times per week for 19 months with interposing periods of complete suspension. Thirty-four foci of signet ring cell carcinoma were found in the antral region of the stomach. The majority of the foci (31 foci) were early cancer, and the remaining foci were invasive cancer. In addition to these lesions, there was \"a single gland cancer\" in which a row of cancer cells was confined to a single gland. The whole gland was composed of two cell layers; the inner layer facing the lumen was normal gastric cells and the outer layer was atypical or neoplastic cells underlaid by the basement membrane. Mitosis was frequently observed on the bottom of the gland. Atypical or neoplastic cells seemed to mature gradually through a process of upward migration with increase in cytoplasmic Alcian blue-PAS and HID-AB positive mucin. Some of the cells rich in mucin moved into the lamina propria. The other cells remained in the flow of the regular cell renewal system of the normal gastric cells and reached the top of the gland. This observation revealed a mode of incipient gastric cancer growth, which starts and spreads within a single gland, before it invades the surrounding lamina propria."}
{"id": "PMID:223135", "title": "Elevated early gastric carcinoma. Differential diagnosis as regards adenomatous polyps.", "content": "Differential diagnostic problems between gastric carcinomas and precancerous lesions with severe dysplasia have become more perceptible with the increasing number of resected early carcinomas. Although such problems come up for all macroscopic and histologic types of gastric cancer they are particularly marked between early carcinomas of the elevated type and adenomatous polyps. Elevated early carcinomas are usually highly differentiated adenocarcinomas with a morphology which often reminds of of adenomas. But sometimes the carcinomas also demonstrate convincing signs of being developed from adenomas. The criterion of distinction between intramucosal carcinomas and adenomas is invasion through the basal membrane, often difficult to evaluate. The morphological relation between elevated early gastric carcinomas and adenomas and the criterion of distinction between them were studied in 20 early gastric carcinomas of the Japanese types I and IIa, 6 intramucosal and 14 submucosal all highly differentiated adenocarcinomas, and in 42 polyps, of which 5 were of the adenomatous type. All lesions were taken from resection specimens. Among the carcinomas 5 demonstrated convincing signs of being malignant transformed adenomas. In addition, 6 carcinomas had a morphology which more or less reminded of adenomas, but their genetic origin was more uncertain. Nine carcinomas revealed no sign of an adenomatous origin. Among the 5 polyps diagnosed as adenomas 2 revealed an extraordinary degree of severe dysplasia which caused uncertainty on the benign diagnosis. The rest of the polyps were without dysplasia. The significance of invasion through the basal membrane as an indispensable factor of distinction between adenoma and carcinoma in the stomach is discussed. It is concluded that the degree of dysplasia can be so severe and the invasion so difficult to evaluate that the classification of some few tumours depends on the subjectivity of the single pathologist. Four of the tumours, 2 adenomas and 2 intramucosal carcinomas, having a remarkable macroscopic appearance like a large mucosal fold are especially mentioned. Their relation to gastric mucosal prolaps is discussed. Furthermore, a tumour apparently demonstrating only a moderate degree of dysplasia, but even so setting up metastases is mentioned in detail.", "contents": "Elevated early gastric carcinoma. Differential diagnosis as regards adenomatous polyps. Differential diagnostic problems between gastric carcinomas and precancerous lesions with severe dysplasia have become more perceptible with the increasing number of resected early carcinomas. Although such problems come up for all macroscopic and histologic types of gastric cancer they are particularly marked between early carcinomas of the elevated type and adenomatous polyps. Elevated early carcinomas are usually highly differentiated adenocarcinomas with a morphology which often reminds of of adenomas. But sometimes the carcinomas also demonstrate convincing signs of being developed from adenomas. The criterion of distinction between intramucosal carcinomas and adenomas is invasion through the basal membrane, often difficult to evaluate. The morphological relation between elevated early gastric carcinomas and adenomas and the criterion of distinction between them were studied in 20 early gastric carcinomas of the Japanese types I and IIa, 6 intramucosal and 14 submucosal all highly differentiated adenocarcinomas, and in 42 polyps, of which 5 were of the adenomatous type. All lesions were taken from resection specimens. Among the carcinomas 5 demonstrated convincing signs of being malignant transformed adenomas. In addition, 6 carcinomas had a morphology which more or less reminded of adenomas, but their genetic origin was more uncertain. Nine carcinomas revealed no sign of an adenomatous origin. Among the 5 polyps diagnosed as adenomas 2 revealed an extraordinary degree of severe dysplasia which caused uncertainty on the benign diagnosis. The rest of the polyps were without dysplasia. The significance of invasion through the basal membrane as an indispensable factor of distinction between adenoma and carcinoma in the stomach is discussed. It is concluded that the degree of dysplasia can be so severe and the invasion so difficult to evaluate that the classification of some few tumours depends on the subjectivity of the single pathologist. Four of the tumours, 2 adenomas and 2 intramucosal carcinomas, having a remarkable macroscopic appearance like a large mucosal fold are especially mentioned. Their relation to gastric mucosal prolaps is discussed. Furthermore, a tumour apparently demonstrating only a moderate degree of dysplasia, but even so setting up metastases is mentioned in detail."}
{"id": "PMID:223136", "title": "Multifocal early gastric cancer of mixed type.", "content": "A report of three selected gastric resection specimens presents the problems of histological classification of individual early gastric cancer, illustrated in discrepancies between macroscopic or endoscopic, and histologic identification. Multifocal origin and different types of gastric cancer are demonstrated in all three cases. Problems related to exact histologic classification of this mixed type are discussed together with the prognosis and surgical consequences.", "contents": "Multifocal early gastric cancer of mixed type. A report of three selected gastric resection specimens presents the problems of histological classification of individual early gastric cancer, illustrated in discrepancies between macroscopic or endoscopic, and histologic identification. Multifocal origin and different types of gastric cancer are demonstrated in all three cases. Problems related to exact histologic classification of this mixed type are discussed together with the prognosis and surgical consequences."}
{"id": "PMID:223138", "title": "The pathogenesis of respiratory viral infection.", "content": "Sendai virus is used as a model to study the histological response and the mechanism of recovery of mice from infection. Although mice infected intranasally do not appear ill, the ciliated columnar cells of the bronchial epithelium undergoes rapid necrosis followed later by repair. Interferon is produced at an early stage of infection and antibody formation follows later. Cyclophosphamide given to mice infected with Sendai virus abolishes the humoral antibody response but not interferon production; the mice develop pneumonic lesions. They cannot eliminate virus and they die. On the other hand, deprivation of 'T' lymphocytes by thymectomy, irradiation and bone marrow reconstitution renders mice more susceptible to Sendai virus but they do not die. The humoral response is thus apparently helped by 'T' lymphocytes and interferon production is not vital for recovery.", "contents": "The pathogenesis of respiratory viral infection. Sendai virus is used as a model to study the histological response and the mechanism of recovery of mice from infection. Although mice infected intranasally do not appear ill, the ciliated columnar cells of the bronchial epithelium undergoes rapid necrosis followed later by repair. Interferon is produced at an early stage of infection and antibody formation follows later. Cyclophosphamide given to mice infected with Sendai virus abolishes the humoral antibody response but not interferon production; the mice develop pneumonic lesions. They cannot eliminate virus and they die. On the other hand, deprivation of 'T' lymphocytes by thymectomy, irradiation and bone marrow reconstitution renders mice more susceptible to Sendai virus but they do not die. The humoral response is thus apparently helped by 'T' lymphocytes and interferon production is not vital for recovery."}
{"id": "PMID:223139", "title": "Interferon induction by adenoviruses.", "content": "All human, simian, bovine and avian adenovirus types tested so far and the canine hepatitis virus induce interferon production in chick cells. This finding indicated this property to be characteristic for viruses belonging to the adenovirus group. Trypsin treatment, which had no effect upon the infectivity, diminished or eliminated the interferon-inducing abilities of crude adenoviruses, and thus the need for a trypsin-sensitive protein in interferon induction was suggested. T antigen and interferon were formed simultaneously in chick embryo fibroblast cells infected with human adenovirus type 12, and therefore the adenovirus-specific T antigen was resistant to the action of endogenous interferon synthetized by the same cells. In chicks inoculated with human types, the appearance of interferon was biphasic: an 'early' and a 'late' interferon could be demonstrated with maximum titre 4 and 10 hr, respectively, after virus infection. In chicks infected with adenoviruses, first interferon production and then a decreased primary immune response to sheep red blood cells was observed. It was assumed that in adenovirus-infected chicks the interferon produced by viral stimulus resulted in a transient immunosuppression.", "contents": "Interferon induction by adenoviruses. All human, simian, bovine and avian adenovirus types tested so far and the canine hepatitis virus induce interferon production in chick cells. This finding indicated this property to be characteristic for viruses belonging to the adenovirus group. Trypsin treatment, which had no effect upon the infectivity, diminished or eliminated the interferon-inducing abilities of crude adenoviruses, and thus the need for a trypsin-sensitive protein in interferon induction was suggested. T antigen and interferon were formed simultaneously in chick embryo fibroblast cells infected with human adenovirus type 12, and therefore the adenovirus-specific T antigen was resistant to the action of endogenous interferon synthetized by the same cells. In chicks inoculated with human types, the appearance of interferon was biphasic: an 'early' and a 'late' interferon could be demonstrated with maximum titre 4 and 10 hr, respectively, after virus infection. In chicks infected with adenoviruses, first interferon production and then a decreased primary immune response to sheep red blood cells was observed. It was assumed that in adenovirus-infected chicks the interferon produced by viral stimulus resulted in a transient immunosuppression."}
{"id": "PMID:223140", "title": "Slow viruses and chronic disease of the central nervous system.", "content": "Although recognized since the 1930s, slow infections have only recently received considerable attention. There are three types, group A (related to the type C RNA viruses), group B (bizarre agents such as scrapie and kuru) and group C (viruses such as measles which normally produce acute infections but which are behaving here in an unusual fashion). These viruses are only united in that they produce disease with excessively long incubation periods. Many slow infections result in neurological diseases and these will be discussed, together with some possible explanations of their action.", "contents": "Slow viruses and chronic disease of the central nervous system. Although recognized since the 1930s, slow infections have only recently received considerable attention. There are three types, group A (related to the type C RNA viruses), group B (bizarre agents such as scrapie and kuru) and group C (viruses such as measles which normally produce acute infections but which are behaving here in an unusual fashion). These viruses are only united in that they produce disease with excessively long incubation periods. Many slow infections result in neurological diseases and these will be discussed, together with some possible explanations of their action."}
{"id": "PMID:223141", "title": "Some aspects of the role of viruses in cancer.", "content": "The cells of tumours induced by many oncogenic DNA viruses, or cells transformed in vitro, contain virus-specific T and transplantation antigens; these have been described for SV40 virus, polyoma virus and adenoviruses. The investigation of viruses as causes of malignant disease in man has sought to establish whether tumour cells possess these virus-specific proteins; however, to date and with the limitations of present techniques, this enquiry has not demonstrated the above viruses as causal of human cancer. More recent studies with herpesvirus type 2 (HSV-2) have shown this virus to transform animal and human cells in culture, and induce cancer in experimental animals: for these reasons, many researchers have suggested that this agent may be an agent of some forms of cancer, in particular carcinoma of the cervix. The possible association of HSV-2 with human malignant disease is discussed.", "contents": "Some aspects of the role of viruses in cancer. The cells of tumours induced by many oncogenic DNA viruses, or cells transformed in vitro, contain virus-specific T and transplantation antigens; these have been described for SV40 virus, polyoma virus and adenoviruses. The investigation of viruses as causes of malignant disease in man has sought to establish whether tumour cells possess these virus-specific proteins; however, to date and with the limitations of present techniques, this enquiry has not demonstrated the above viruses as causal of human cancer. More recent studies with herpesvirus type 2 (HSV-2) have shown this virus to transform animal and human cells in culture, and induce cancer in experimental animals: for these reasons, many researchers have suggested that this agent may be an agent of some forms of cancer, in particular carcinoma of the cervix. The possible association of HSV-2 with human malignant disease is discussed."}
{"id": "PMID:223142", "title": "Cytomegalovirus-associated gastric ulcer simulating malignancy.", "content": "A case is reported of cytomegalovirus (CMV) infection with radiological, gastroscopic and histological appearances which led to a mistaken diagnosis of carcinoma of the stomach.", "contents": "Cytomegalovirus-associated gastric ulcer simulating malignancy. A case is reported of cytomegalovirus (CMV) infection with radiological, gastroscopic and histological appearances which led to a mistaken diagnosis of carcinoma of the stomach."}
{"id": "PMID:223143", "title": "[Determination of organic elements in histological sections (author's transl)].", "content": "In the microscopic differential diagnosis of fibrosing lung processes organic deposits are often encountered which defy identification by histological methods. Assessment of the aetiological significance of these deposits depends on an accurate analysis. Energy-dispersive X-ray microanalysis with an electron microscope provides the means to identify organic deposits in the tissues. Such analyses, which do not require elaborate techniques, show up the type and structure of the deposits and the topographical relation to the lung lesion. They provide detailed information for assessing pulmonary lesions caused by fibrosis-inducing dusts.", "contents": "[Determination of organic elements in histological sections (author's transl)]. In the microscopic differential diagnosis of fibrosing lung processes organic deposits are often encountered which defy identification by histological methods. Assessment of the aetiological significance of these deposits depends on an accurate analysis. Energy-dispersive X-ray microanalysis with an electron microscope provides the means to identify organic deposits in the tissues. Such analyses, which do not require elaborate techniques, show up the type and structure of the deposits and the topographical relation to the lung lesion. They provide detailed information for assessing pulmonary lesions caused by fibrosis-inducing dusts."}
{"id": "PMID:223146", "title": "Enzyme activities in endothelial cells and smooth muscle cells from swine aorta.", "content": "In populations of cultured arterial endothelial and smooth muscle cells grown under the same conditions, we have measured the total activity per cell of 10 enzymes commonly used as \"markers\" for subcellular organelles: NADH: ferricyanide reductase, NADH:cytochrome c reductase (rotenone insensitive). NADPH:cytochrome c reductase, alpha-glucosidase, 5'-nucleotidase, alkaline phosphodiesterase I, cytochrome oxidase, monoamine oxidase, cathepsin D, and N-acetyl-beta-glucosaminidase. Significant differences between the cell types were found for 7 of the 10 enzymes tested. The total activity of 5'-nucleotidase in cultured smooth muscle cells was 17 times that of cultured endothelial cells. Comparison of the activities in the two cell types freshly collected and in culture showed that the difference in 5'-nucleotidase in cultured cells is due principally to loss of activity from endothelial cells, suggesting that this activity is regulated differently in the two cell types. In both cell types cathepsin D activity rose during culture.", "contents": "Enzyme activities in endothelial cells and smooth muscle cells from swine aorta. In populations of cultured arterial endothelial and smooth muscle cells grown under the same conditions, we have measured the total activity per cell of 10 enzymes commonly used as \"markers\" for subcellular organelles: NADH: ferricyanide reductase, NADH:cytochrome c reductase (rotenone insensitive). NADPH:cytochrome c reductase, alpha-glucosidase, 5'-nucleotidase, alkaline phosphodiesterase I, cytochrome oxidase, monoamine oxidase, cathepsin D, and N-acetyl-beta-glucosaminidase. Significant differences between the cell types were found for 7 of the 10 enzymes tested. The total activity of 5'-nucleotidase in cultured smooth muscle cells was 17 times that of cultured endothelial cells. Comparison of the activities in the two cell types freshly collected and in culture showed that the difference in 5'-nucleotidase in cultured cells is due principally to loss of activity from endothelial cells, suggesting that this activity is regulated differently in the two cell types. In both cell types cathepsin D activity rose during culture."}
{"id": "PMID:223144", "title": "[Localization of retinylphosphatase activity in subcellular fractions of rat liver].", "content": "Enzymic hydrolysis of retinyl phosphate in subcellular fractions of the rat liver has been investigated. A quantitative method of measuring activity of retinyl phosphatase has been developed. The method is based on the isolation of labeled retinol, the substance formed from chemically synthesized labeled retinyl phosphate through enzymatic hydrolysis. It has been shown that the major quantity of retinyl phosphatase activity (75%) with a specific activity of 80 micrograms retinyl phosphate hydrolyzed for 30 min/mg protein at 30 degrees C occurs in plasmatic membranes.", "contents": "[Localization of retinylphosphatase activity in subcellular fractions of rat liver]. Enzymic hydrolysis of retinyl phosphate in subcellular fractions of the rat liver has been investigated. A quantitative method of measuring activity of retinyl phosphatase has been developed. The method is based on the isolation of labeled retinol, the substance formed from chemically synthesized labeled retinyl phosphate through enzymatic hydrolysis. It has been shown that the major quantity of retinyl phosphatase activity (75%) with a specific activity of 80 micrograms retinyl phosphate hydrolyzed for 30 min/mg protein at 30 degrees C occurs in plasmatic membranes."}
{"id": "PMID:223147", "title": "Phosphorylation and inactivation of glycogen synthase by phosphorylase kinase.", "content": "Skeletal muscle glycogen a4-synthase (EC 2.4.1.11) has been purified free of all synthase kinase and phosphatase activities by chromatography on a Glc-N-6-P-Sepharose affinity column and then on a phosphocellulose column. This preparation of glycogen synthase was tested as a substrate for purified skeletal muscle phosphorylase kinase (ATP:phosphorylase-b phosphotransferase, EC 2.7.1.38). Phosphorylase kinase (1-10 microgram/ml or 0.03-0.3 microM) catalyzes rapid phosphorylation of glycogen synthase (4.5 microM) associated with conversion of the active a form to the less active b form. In the reaction, greater than 95% of the 32P incorporation from [gamma-32P]ATP goes into the synthase subunit almost exclusively in the trypsin-insensitive region which is responsible for synthase a-to-b conversion. Synthase phosphorylation or inactivations catalyzed by phosphorylase kinase is blocked by ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, is ATP dependent, is 10-fold more rapid at pH 8.6 than at pH 6.8, and is increased 10-fold by prior activation of the phosphorylase kinase with MgATP and cyclic AMP. With activated phosphorylase kinase at pH 8.2 the apparent Km and Vmax are approximately 70 microM and 4 mumol/min per mg with glycogen synthase and 70 microM and 9 mumol/min per mg with phosphorylase as substrate. It is concluded that glycogen synthase is a substrate in vitro for phosphorylase kinase, a Ca2+-dependent enzyme. The possible physiological significance of this reaction is discussed.", "contents": "Phosphorylation and inactivation of glycogen synthase by phosphorylase kinase. Skeletal muscle glycogen a4-synthase (EC 2.4.1.11) has been purified free of all synthase kinase and phosphatase activities by chromatography on a Glc-N-6-P-Sepharose affinity column and then on a phosphocellulose column. This preparation of glycogen synthase was tested as a substrate for purified skeletal muscle phosphorylase kinase (ATP:phosphorylase-b phosphotransferase, EC 2.7.1.38). Phosphorylase kinase (1-10 microgram/ml or 0.03-0.3 microM) catalyzes rapid phosphorylation of glycogen synthase (4.5 microM) associated with conversion of the active a form to the less active b form. In the reaction, greater than 95% of the 32P incorporation from [gamma-32P]ATP goes into the synthase subunit almost exclusively in the trypsin-insensitive region which is responsible for synthase a-to-b conversion. Synthase phosphorylation or inactivations catalyzed by phosphorylase kinase is blocked by ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, is ATP dependent, is 10-fold more rapid at pH 8.6 than at pH 6.8, and is increased 10-fold by prior activation of the phosphorylase kinase with MgATP and cyclic AMP. With activated phosphorylase kinase at pH 8.2 the apparent Km and Vmax are approximately 70 microM and 4 mumol/min per mg with glycogen synthase and 70 microM and 9 mumol/min per mg with phosphorylase as substrate. It is concluded that glycogen synthase is a substrate in vitro for phosphorylase kinase, a Ca2+-dependent enzyme. The possible physiological significance of this reaction is discussed."}
{"id": "PMID:223145", "title": "[Regulation of the activity of 3', 5'-cyclic AMP phosphodiesterase by pancreatic hormones].", "content": "The character of the insulin effect on the activity of phosphodiesterase (PDE) cAMP of various subcellular localization was studied in the liver of normal and diabetic rats. As a result of kinetic investigations for PDE cAMP preparations of the plasma membranes there were obtained kinetic characteristics of two PDE forms, differing by their affinity to the substrate. For the both PDE cAMP forms stimulation of the activity with insulin was indicated. In examining the insulin effect on the activity of PDE cAMP of the liver of rats with streptozotocin-induced diabetes there was revealed a significant effect of the hormone on the kinetics of the enzyme with a high affinity to cAMP only.", "contents": "[Regulation of the activity of 3', 5'-cyclic AMP phosphodiesterase by pancreatic hormones]. The character of the insulin effect on the activity of phosphodiesterase (PDE) cAMP of various subcellular localization was studied in the liver of normal and diabetic rats. As a result of kinetic investigations for PDE cAMP preparations of the plasma membranes there were obtained kinetic characteristics of two PDE forms, differing by their affinity to the substrate. For the both PDE cAMP forms stimulation of the activity with insulin was indicated. In examining the insulin effect on the activity of PDE cAMP of the liver of rats with streptozotocin-induced diabetes there was revealed a significant effect of the hormone on the kinetics of the enzyme with a high affinity to cAMP only."}
{"id": "PMID:223148", "title": "Segments of simian virus 40 DNA spanning most of the leader sequence of the major late viral messenger RNA are dispensable.", "content": "A highly specific procedure for the isolation of deletion mutants is described. The size and location of the deletions can be predetermined. By this method a series of deletion mutants mapping within and near the untranslated 5' leader sequence of the late 16S mRNA of simian virus 40 have been isolated. The boundaries of the deletions have been accurately determined by DNA sequence analysis. The deletions range from 20 to 223 nucleotides. All these deletions mutants are viable and grow without helper virus. The largest of these deletions removes the entire leader sequence except for six nucleotides at the 3' end that are probably involved in covalent linkage with the 5' end of the body of the mRNA located 937 nucleotides away on the genome. Three of the deletion mutants remove the 5' end of the leader that normally bears the cap structure of the mRNA. A large segment immediately preceding the leader sequence is also removed in one of these mutants, ruling out the generation of the 5' end of the mRNA via initiation of transcription at this point. The circularization of linear infecting DNA producing the DNA of the deletion mutants proceeds mainly by way of blunt end ligation in vivo.", "contents": "Segments of simian virus 40 DNA spanning most of the leader sequence of the major late viral messenger RNA are dispensable. A highly specific procedure for the isolation of deletion mutants is described. The size and location of the deletions can be predetermined. By this method a series of deletion mutants mapping within and near the untranslated 5' leader sequence of the late 16S mRNA of simian virus 40 have been isolated. The boundaries of the deletions have been accurately determined by DNA sequence analysis. The deletions range from 20 to 223 nucleotides. All these deletions mutants are viable and grow without helper virus. The largest of these deletions removes the entire leader sequence except for six nucleotides at the 3' end that are probably involved in covalent linkage with the 5' end of the body of the mRNA located 937 nucleotides away on the genome. Three of the deletion mutants remove the 5' end of the leader that normally bears the cap structure of the mRNA. A large segment immediately preceding the leader sequence is also removed in one of these mutants, ruling out the generation of the 5' end of the mRNA via initiation of transcription at this point. The circularization of linear infecting DNA producing the DNA of the deletion mutants proceeds mainly by way of blunt end ligation in vivo."}
{"id": "PMID:223149", "title": "Cyclic nucleotide phosphodiesterase activity in 10-nm filaments and microtubule preparations from bovine brain.", "content": "Cyclic nucleotide phosphodiesterase activity (3':5'-cyclic-AMP 5'-nucleotidohydrolase, EC 3.1.4.17), which is activatable by Ca(2+)-dependent regulator protein (CDR), has been identified in cycled microtubule preparations from bovine brain. By using various methods to fractionate the microtubule preparation into subfractions (e.g., phosphocellulose chromatography to obtain purified 6S tubulin and soluble microtubule-associated proteins, and gel exclusion chromatography on Bio-Gel A-150m to obtain 10-nm filaments), we found that all the fractions exhibited some enzymic activity, but that most of the phosphodiesterase activity was localized in the 10-nm filament fraction. By using cyclic GMP as substrate, a specific activity of 921 +/- 168 pmol/mg of filament protein.min was determined. Also, 10-nm filaments were prepared directly from brain homogenates by differential centrifugation and gel exclusion chromatography. This fraction also contained phosphodiesterase activity but of slightly lower specific activity (752 +/- 9 pmol/mg of protein.min). The filament-associated enzymic activity was stable during storage (-70 degrees C) and to several salt extractions at moderate ionic strength (0.5 M); the latter finding indicates that the phosphodiesterase is not adsorbed to the filaments via nonspecific electrostatic interactions. Although a chelating agent was present in the initial homogenization buffer and generally in all buffers used in preparing fractions, an activator of a smooth muscle phosphodiesterase was released upon boiling the 10-nm filaments. This activator obtained in the boiled supernatant was Ca(2+)-sensitive, trifluoperazine-sensitive, and stimulated smooth muscle phosphodiesterase to nearly the same extent as purified (exogenous) CDR; thus, it probably represents filament-associated CDR.", "contents": "Cyclic nucleotide phosphodiesterase activity in 10-nm filaments and microtubule preparations from bovine brain. Cyclic nucleotide phosphodiesterase activity (3':5'-cyclic-AMP 5'-nucleotidohydrolase, EC 3.1.4.17), which is activatable by Ca(2+)-dependent regulator protein (CDR), has been identified in cycled microtubule preparations from bovine brain. By using various methods to fractionate the microtubule preparation into subfractions (e.g., phosphocellulose chromatography to obtain purified 6S tubulin and soluble microtubule-associated proteins, and gel exclusion chromatography on Bio-Gel A-150m to obtain 10-nm filaments), we found that all the fractions exhibited some enzymic activity, but that most of the phosphodiesterase activity was localized in the 10-nm filament fraction. By using cyclic GMP as substrate, a specific activity of 921 +/- 168 pmol/mg of filament protein.min was determined. Also, 10-nm filaments were prepared directly from brain homogenates by differential centrifugation and gel exclusion chromatography. This fraction also contained phosphodiesterase activity but of slightly lower specific activity (752 +/- 9 pmol/mg of protein.min). The filament-associated enzymic activity was stable during storage (-70 degrees C) and to several salt extractions at moderate ionic strength (0.5 M); the latter finding indicates that the phosphodiesterase is not adsorbed to the filaments via nonspecific electrostatic interactions. Although a chelating agent was present in the initial homogenization buffer and generally in all buffers used in preparing fractions, an activator of a smooth muscle phosphodiesterase was released upon boiling the 10-nm filaments. This activator obtained in the boiled supernatant was Ca(2+)-sensitive, trifluoperazine-sensitive, and stimulated smooth muscle phosphodiesterase to nearly the same extent as purified (exogenous) CDR; thus, it probably represents filament-associated CDR."}
{"id": "PMID:223150", "title": "Mechanism for discrimination between viral and host mRNA in interferon-treated cells.", "content": "In extracts of interferon-treated HeLa cells, RNA covalently linked to double-stranded RNA (dsRNA) is preferentially degraded compared with mRNA not linked in dsRNA. This was established by following the degradation of poly(A)-containing mRNA annealed with poly(U), of poly(C)-containing encephalomyocarditis virus RNA annealed with poly(I), and of the replicative intermediate of the virus isolated from infected cells. In extracts of interferon-treated cells, dsRNA promotes the synthesis of a series of oligonucleotides, designated (2'-5')oligo(A), which in turn activate an endonuclease. Several lines of evidence suggest that the (2'-5')oligo(A) polymerase/endonuclease system is involved in the preferential degradation of mRNA linked to dsRNA. Conditions that prevent synthesis of (2'-5')oligo(A) prevent this preferential degradation, whereas addition of (2'-5')oligo(A) or conditions that favor its synthesis result in degradation of mRNA both linked and not linked to dsRNA. These results are best explained by a localized activation of the endonuclease near the dsRNA region of our model substrates. We propose that in infected cells activation of the endonuclease takes place near the replicative intermediates of RNA viruses. The replicative intermediates of encephalomyocarditis virus promote synthesis of (2'-5')-oligo(A) in extracts of interferon-treated cells and are degraded to a 20S \"core\" resistant to digestion with RNase A. This mechanism may be responsible for discrimination between viral and cellular mRNA in interferon-treated cells.", "contents": "Mechanism for discrimination between viral and host mRNA in interferon-treated cells. In extracts of interferon-treated HeLa cells, RNA covalently linked to double-stranded RNA (dsRNA) is preferentially degraded compared with mRNA not linked in dsRNA. This was established by following the degradation of poly(A)-containing mRNA annealed with poly(U), of poly(C)-containing encephalomyocarditis virus RNA annealed with poly(I), and of the replicative intermediate of the virus isolated from infected cells. In extracts of interferon-treated cells, dsRNA promotes the synthesis of a series of oligonucleotides, designated (2'-5')oligo(A), which in turn activate an endonuclease. Several lines of evidence suggest that the (2'-5')oligo(A) polymerase/endonuclease system is involved in the preferential degradation of mRNA linked to dsRNA. Conditions that prevent synthesis of (2'-5')oligo(A) prevent this preferential degradation, whereas addition of (2'-5')oligo(A) or conditions that favor its synthesis result in degradation of mRNA both linked and not linked to dsRNA. These results are best explained by a localized activation of the endonuclease near the dsRNA region of our model substrates. We propose that in infected cells activation of the endonuclease takes place near the replicative intermediates of RNA viruses. The replicative intermediates of encephalomyocarditis virus promote synthesis of (2'-5')-oligo(A) in extracts of interferon-treated cells and are degraded to a 20S \"core\" resistant to digestion with RNase A. This mechanism may be responsible for discrimination between viral and cellular mRNA in interferon-treated cells."}
{"id": "PMID:223151", "title": "Multistep regulatory system for activation of a cyclic AMP-independent eukaryotic initiation factor 2 kinase.", "content": "Three functionally related components that block peptide initiation have been identified in lysates of rabbit reticulocytes. The components function consecutively in a cascade type sequence of reactions to cause phosphorylation of eukaryotic peptide initiation factor 2 (eIF-2). The eIF-2 kinase activated as part of this sequence has been tentatively identified as the same protein kinase that is activated by heme deficiency as part of the hemin-controlled repressor (HCR) system. The first component in the sequence is heat stable and can be reversibly activated by heat or pressure. It activates a second, heat-labile, component that in turn directly or indirectly activates the hemin-controlled eIF-2 kinase. This heat-labile component appears to function through proteolysis. This reaction sequence is not detectably affected by heme or cyclic AMP and thus appears to provide an alternative mechanism, independent of heme, for activation of the cyclic AMP-independent eIF-2 kinase of the HCR system.", "contents": "Multistep regulatory system for activation of a cyclic AMP-independent eukaryotic initiation factor 2 kinase. Three functionally related components that block peptide initiation have been identified in lysates of rabbit reticulocytes. The components function consecutively in a cascade type sequence of reactions to cause phosphorylation of eukaryotic peptide initiation factor 2 (eIF-2). The eIF-2 kinase activated as part of this sequence has been tentatively identified as the same protein kinase that is activated by heme deficiency as part of the hemin-controlled repressor (HCR) system. The first component in the sequence is heat stable and can be reversibly activated by heat or pressure. It activates a second, heat-labile, component that in turn directly or indirectly activates the hemin-controlled eIF-2 kinase. This heat-labile component appears to function through proteolysis. This reaction sequence is not detectably affected by heme or cyclic AMP and thus appears to provide an alternative mechanism, independent of heme, for activation of the cyclic AMP-independent eIF-2 kinase of the HCR system."}
{"id": "PMID:223152", "title": "Protein kinase activity associated with simian virus 40 T antigen.", "content": "Incubation of simian virus 40 (SV40) tumor (T) antigen-containing immunoprecipitates with [gamma-32P]ATP results in the incorporation of radioactive phosphate into large T antigen. Highly purified preparations of large T antigen from a SV40-transformed cell line, SV80, are able to catalyze the phosphorylation of a known phosphate acceptor, casein. The kinase activity migrates with large T antigen through multiple purification steps. Sedimentation analysis under non-T-antigen-aggregating conditions reveals that kinase activity and the immunoreactive protein comigrate as a 6S structure. The kinase activity of purified preparations of large T antigen can be specifically adsorbed to solid-phase anti-T IgG, and partially purified T antigen from a SV40 tsA transformation is thermolabile in its ability to phosphorylate casein when compared to comparably purified wild-type T antigen. These observations indicate that the SV40 large T antigen is closely associated with protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37) activity.", "contents": "Protein kinase activity associated with simian virus 40 T antigen. Incubation of simian virus 40 (SV40) tumor (T) antigen-containing immunoprecipitates with [gamma-32P]ATP results in the incorporation of radioactive phosphate into large T antigen. Highly purified preparations of large T antigen from a SV40-transformed cell line, SV80, are able to catalyze the phosphorylation of a known phosphate acceptor, casein. The kinase activity migrates with large T antigen through multiple purification steps. Sedimentation analysis under non-T-antigen-aggregating conditions reveals that kinase activity and the immunoreactive protein comigrate as a 6S structure. The kinase activity of purified preparations of large T antigen can be specifically adsorbed to solid-phase anti-T IgG, and partially purified T antigen from a SV40 tsA transformation is thermolabile in its ability to phosphorylate casein when compared to comparably purified wild-type T antigen. These observations indicate that the SV40 large T antigen is closely associated with protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37) activity."}
{"id": "PMID:223153", "title": "DNA endonucleases associated with the avian myeloblastosis virus DNA polymerase.", "content": "A DNA endonuclease, Endo-I, which cleaves superhelical DNAs, has been isolated from avian myeloblastosis virions stripped of their coats by mild detergent treatment. The enzyme has a broad pH optimum around 7.5-8.0 and requires Mg2+ for activity. A second endonuclease, Endo-II, with a requirement for Mn2+, also present in viral cores, copurified with avian myeloblastosis virus alpha beta DNA polymerase (reverse transcriptase, RNA-dependent DNA nucleotidyltransferase) and similarly cleaved superhelical DNAs. Heat denaturation and sodium fluoride and N-ethylmaleimide inhibition studies were carried out to demonstrate a possible relationship between the two endonucleases and the viral DNA polymerase and RNase H activities. It appears that Endo-II may be an intrinsic activity of the polymerase.", "contents": "DNA endonucleases associated with the avian myeloblastosis virus DNA polymerase. A DNA endonuclease, Endo-I, which cleaves superhelical DNAs, has been isolated from avian myeloblastosis virions stripped of their coats by mild detergent treatment. The enzyme has a broad pH optimum around 7.5-8.0 and requires Mg2+ for activity. A second endonuclease, Endo-II, with a requirement for Mn2+, also present in viral cores, copurified with avian myeloblastosis virus alpha beta DNA polymerase (reverse transcriptase, RNA-dependent DNA nucleotidyltransferase) and similarly cleaved superhelical DNAs. Heat denaturation and sodium fluoride and N-ethylmaleimide inhibition studies were carried out to demonstrate a possible relationship between the two endonucleases and the viral DNA polymerase and RNase H activities. It appears that Endo-II may be an intrinsic activity of the polymerase."}
{"id": "PMID:223154", "title": "Ion-channel component of cytochrome oxidase.", "content": "Cytochrome oxidase is resolvable into an electron transfer complex and an ion transfer complex. The ion transfer complex has been shown to have the capability for inducing nonspecific ion transport into liposomes. Subunit I of cytochrome oxidase has been identified as an ion-channel-forming protein.", "contents": "Ion-channel component of cytochrome oxidase. Cytochrome oxidase is resolvable into an electron transfer complex and an ion transfer complex. The ion transfer complex has been shown to have the capability for inducing nonspecific ion transport into liposomes. Subunit I of cytochrome oxidase has been identified as an ion-channel-forming protein."}
{"id": "PMID:223155", "title": "Poliovirus replicase: a soluble enzyme able to initiate copying of poliovirus RNA.", "content": "The soluble phase of the cytoplasm of poliovirus-infected cells contains an enzymatic activity able to copy RNA without an added primer. This replicase activity has been purified 60-fold; it is absent from uninfected cells. Poly(U) polymerase activity copurifies with replicase activity. Although less pure replicase fractions copy a variety of RNAs, purer fractions respond better to poliovirus RNA than to other viral RNAs. Even the less pure fractions make a specific copy of the added template, as shown by hybridization of the product to its template RNA but not to other RNAs. Among homopolymers only poly(A)-oligo(U) was copied by the replicase; other primed homopolymer templates were inactive.", "contents": "Poliovirus replicase: a soluble enzyme able to initiate copying of poliovirus RNA. The soluble phase of the cytoplasm of poliovirus-infected cells contains an enzymatic activity able to copy RNA without an added primer. This replicase activity has been purified 60-fold; it is absent from uninfected cells. Poly(U) polymerase activity copurifies with replicase activity. Although less pure replicase fractions copy a variety of RNAs, purer fractions respond better to poliovirus RNA than to other viral RNAs. Even the less pure fractions make a specific copy of the added template, as shown by hybridization of the product to its template RNA but not to other RNAs. Among homopolymers only poly(A)-oligo(U) was copied by the replicase; other primed homopolymer templates were inactive."}
{"id": "PMID:223156", "title": "Physical modifications of rhodopsin boundary lipids in lecithin-rhodopsin complexes: a spin-label study.", "content": "The microviscosity of rhodopsin boundary lipids was studied with a spin-labeled fatty acid covalently attached to rhodopsin, in rhodopsin-egg lecithin vesicles. When the lipid-to-protein ratio was high (500:1, mole to mole), only narrow peaks were visible in electron paramagnetic resonance spectrum at 37 degrees C. This enabled us to show that, under these conditions, not more than 10% of the probes have their motion strongly restricted by the proximity of the protein. When the temperature was reduced, a second component characteristic of strong immobilization appeared. It corresponds to 50% of the signal at -5 degrees C. At all temperatures reduction of the lipid-to-protein ratio also resulted in an increase of the amount of immobilized lipid. These results show that the rhodopsin boundary layer under physiological conditions is associated with low microviscosity. However, low temperatures, low lipid-to-protein ratios, or combinations of the two can induce dramatic modifications of the physical state of the boundary lipids, which under these conditions may no longer be representative of the functional biological system. These results are relevant to the general theory of lipid-protein interaction.", "contents": "Physical modifications of rhodopsin boundary lipids in lecithin-rhodopsin complexes: a spin-label study. The microviscosity of rhodopsin boundary lipids was studied with a spin-labeled fatty acid covalently attached to rhodopsin, in rhodopsin-egg lecithin vesicles. When the lipid-to-protein ratio was high (500:1, mole to mole), only narrow peaks were visible in electron paramagnetic resonance spectrum at 37 degrees C. This enabled us to show that, under these conditions, not more than 10% of the probes have their motion strongly restricted by the proximity of the protein. When the temperature was reduced, a second component characteristic of strong immobilization appeared. It corresponds to 50% of the signal at -5 degrees C. At all temperatures reduction of the lipid-to-protein ratio also resulted in an increase of the amount of immobilized lipid. These results show that the rhodopsin boundary layer under physiological conditions is associated with low microviscosity. However, low temperatures, low lipid-to-protein ratios, or combinations of the two can induce dramatic modifications of the physical state of the boundary lipids, which under these conditions may no longer be representative of the functional biological system. These results are relevant to the general theory of lipid-protein interaction."}
{"id": "PMID:223157", "title": "Stimulation of sugar uptake and glycolysis in chicken embryo fibroblasts by the major glycoprotein from avian myeloblastosis virus.", "content": "Addition of purified major glycoprotein from avian myeloblastosis virus to growing or quiescent chicken embryo fibroblasts rapidly stimulates the rate of hexose transport and increases the lactic acid production. These stimulatory effects are dependent on the time of exposure and the dose of viral glycoprotein. In contrast, the glycoprotein only marginally affects hexose transport in chicken cells transformed by Rous sarcoma virus. Some effects of the glycoprotein on serum-starved quiescent cells were similar to those observed upon  re-addition of serum; however, the viral glycoprotein did not stimulate DNA synthesis. Quiescent cells stimulated by saturating levels of serum showed little further stimulation of hexose uptake upon exposure to viral glycoprotein for 3 hr. This behavior suggests that the glycoprotein may be acting on a system that is also a target for serum action.", "contents": "Stimulation of sugar uptake and glycolysis in chicken embryo fibroblasts by the major glycoprotein from avian myeloblastosis virus. Addition of purified major glycoprotein from avian myeloblastosis virus to growing or quiescent chicken embryo fibroblasts rapidly stimulates the rate of hexose transport and increases the lactic acid production. These stimulatory effects are dependent on the time of exposure and the dose of viral glycoprotein. In contrast, the glycoprotein only marginally affects hexose transport in chicken cells transformed by Rous sarcoma virus. Some effects of the glycoprotein on serum-starved quiescent cells were similar to those observed upon  re-addition of serum; however, the viral glycoprotein did not stimulate DNA synthesis. Quiescent cells stimulated by saturating levels of serum showed little further stimulation of hexose uptake upon exposure to viral glycoprotein for 3 hr. This behavior suggests that the glycoprotein may be acting on a system that is also a target for serum action."}
{"id": "PMID:223158", "title": "Functional characteristics of dispersed rat submandibular cells.", "content": "Rat submandibular gland cells have been obtained through enzymatic dispersion using chromatographically purified collagenase (EC 3.4.24.3) and hyaluronidase (EC 3.2.1.35) and gentle mechanical force. The recovery of viable cells after the isolation procedure was 59% on the basis of total glandular DNA content. Approximately 60% of the total cell population consisted of acinar cells; less than 8% were immature granular duct cells; and the remainder were intercalated duct, striated duct, and myoepithelial cells. Most of the acinar cells were in acinar-intercalated duct complexes. The integrity of the isolated cells was substantiated by their exclusion of trypan blue, intracellular electrolyte composition, incorporation of [14C]glucosamine into trichloroacetic acid + phosphotungstic acid precipitable material at a linear rate for 1.5 hr, secretory responses to parasympathomimetic and sympathomimetic stimulation, and morphologic integrity as determined by light and electron microscopy. The cholinergic receptors were characterized through investigation of the net transmembrane flux of K+ in response to carbamoylcholine. The alpha-adrenergic receptors were characterized by investigating the net transmembrane flux of K+ in response to norepinephrine stimulation and the beta-adrenergic receptors were characterized by determining the rate of secretion of 14C-labeled mucin after isoproterenol stimulation. A high degree of sensitivity to both cholinergic and adrenergic secretagogues was observed.", "contents": "Functional characteristics of dispersed rat submandibular cells. Rat submandibular gland cells have been obtained through enzymatic dispersion using chromatographically purified collagenase (EC 3.4.24.3) and hyaluronidase (EC 3.2.1.35) and gentle mechanical force. The recovery of viable cells after the isolation procedure was 59% on the basis of total glandular DNA content. Approximately 60% of the total cell population consisted of acinar cells; less than 8% were immature granular duct cells; and the remainder were intercalated duct, striated duct, and myoepithelial cells. Most of the acinar cells were in acinar-intercalated duct complexes. The integrity of the isolated cells was substantiated by their exclusion of trypan blue, intracellular electrolyte composition, incorporation of [14C]glucosamine into trichloroacetic acid + phosphotungstic acid precipitable material at a linear rate for 1.5 hr, secretory responses to parasympathomimetic and sympathomimetic stimulation, and morphologic integrity as determined by light and electron microscopy. The cholinergic receptors were characterized through investigation of the net transmembrane flux of K+ in response to carbamoylcholine. The alpha-adrenergic receptors were characterized by investigating the net transmembrane flux of K+ in response to norepinephrine stimulation and the beta-adrenergic receptors were characterized by determining the rate of secretion of 14C-labeled mucin after isoproterenol stimulation. A high degree of sensitivity to both cholinergic and adrenergic secretagogues was observed."}
{"id": "PMID:223159", "title": "Sites of sequence variability in Epstein-Barr virus DNA from different sources.", "content": "The intracellular Epstein-Barr virus (EBV) DNA present in virus-transformed cells was partly purified from 23 cell lines or biopsies of Burkitt lymphoma, nasopharyngeal carcinoma, infectious mononucleosis, or healthy carrier origin. Such DNA was cleaved in fragments (A-K) of molecular weights between 1 x 10(6) and 30 x 10(6) with restriction enzyme EcoRI, and these fragments were analyzed by standard methods involving agarose gel electrophoresis, transfer to nitrocellulose filters, and hybridization with radioactive EBV DNA or complementary RNA. Sequence variability among different EBV DNA isolates was largely confined to the A, C, and I fragments. These results are discussed in relation to the linkage map of the EcoRI fragments of EBV DNA. The EcoRI cleavage pattern of intracellular viral DNA of an EBV-like virus from baboon cells, Herpesvirus papio, was entirely different from that of human EBV isolates.", "contents": "Sites of sequence variability in Epstein-Barr virus DNA from different sources. The intracellular Epstein-Barr virus (EBV) DNA present in virus-transformed cells was partly purified from 23 cell lines or biopsies of Burkitt lymphoma, nasopharyngeal carcinoma, infectious mononucleosis, or healthy carrier origin. Such DNA was cleaved in fragments (A-K) of molecular weights between 1 x 10(6) and 30 x 10(6) with restriction enzyme EcoRI, and these fragments were analyzed by standard methods involving agarose gel electrophoresis, transfer to nitrocellulose filters, and hybridization with radioactive EBV DNA or complementary RNA. Sequence variability among different EBV DNA isolates was largely confined to the A, C, and I fragments. These results are discussed in relation to the linkage map of the EcoRI fragments of EBV DNA. The EcoRI cleavage pattern of intracellular viral DNA of an EBV-like virus from baboon cells, Herpesvirus papio, was entirely different from that of human EBV isolates."}
{"id": "PMID:223160", "title": "Vp1 affects intracellular localization of Vp3 polypeptide during simian virus 40 infection.", "content": "In order to understand the functions of simian virus 40 genes, permissive cells (TC7) were infected with mutants temperature sensitive in the complementation groups A, B, C, BC, and D at permissive and nonpermissive temperatures. Cells were examined for the localization of viral polypeptide antigens by immunofluorescent staining with monospecific antibodies. The results are as follows: (i) The appearance of Vp1 antigen in cells infected by tsB, C, or BC mutants was not affected appreciably by the mutations. (ii) The appearance of Vp3 antigen was affected by the mutations in B, C, or BC. Vp3 antigen is confined to the nuclei in cells infected by wild-type virus. With mutant virus infection, Vp3 antigen is found in the cytoplasm, perinuclear region, and nucleoli. (iii) The tsD mutants and the tsA mutants did not express either Vp1 or Vp3 antigens at the nonpermissive temperature. (iv) Nucleoli seem to play an essential role in the biosynthesis and assembly of viral polypeptides. Thus, mutations in any one of complementation groups B, C, or BC, which are within the structural gene for Vp1, cause an alteration of intracellular distribution of another late gene product, Vp3. These results suggest that the amino acid sequences of Vp1 polypeptide play a role(s) in the transport of viral antigens across internal membranes or in virus assembly processes or in both.", "contents": "Vp1 affects intracellular localization of Vp3 polypeptide during simian virus 40 infection. In order to understand the functions of simian virus 40 genes, permissive cells (TC7) were infected with mutants temperature sensitive in the complementation groups A, B, C, BC, and D at permissive and nonpermissive temperatures. Cells were examined for the localization of viral polypeptide antigens by immunofluorescent staining with monospecific antibodies. The results are as follows: (i) The appearance of Vp1 antigen in cells infected by tsB, C, or BC mutants was not affected appreciably by the mutations. (ii) The appearance of Vp3 antigen was affected by the mutations in B, C, or BC. Vp3 antigen is confined to the nuclei in cells infected by wild-type virus. With mutant virus infection, Vp3 antigen is found in the cytoplasm, perinuclear region, and nucleoli. (iii) The tsD mutants and the tsA mutants did not express either Vp1 or Vp3 antigens at the nonpermissive temperature. (iv) Nucleoli seem to play an essential role in the biosynthesis and assembly of viral polypeptides. Thus, mutations in any one of complementation groups B, C, or BC, which are within the structural gene for Vp1, cause an alteration of intracellular distribution of another late gene product, Vp3. These results suggest that the amino acid sequences of Vp1 polypeptide play a role(s) in the transport of viral antigens across internal membranes or in virus assembly processes or in both."}
{"id": "PMID:223161", "title": "Demonstration of low density lipoprotein receptors in mouse teratocarcinoma stem cells and description of a method for producing receptor-deficient mutant mice.", "content": "Familial hypercholesterolemia, a widespread human genetic disorder implicated in vascular and coronary disease, has had no laboratory animal counterpart that would enable the pathogenesis to be analyzed and drugs to be tested in vivo. The primary lesion in some patients is known to occur in the cells' initial handling of the major cholesterol-carrying lipoprotein of plasma. It entails a deficiency in the specific cell surface receptor that binds low density lipoprotein (LDL), with a consequent alteration in the control of cholesterol metabolism. The present study was undertaken to devise a practical scheme for producing, from developmentally versatile mouse teratocarcinoma stem cells, whole-animal models with a comparable genetic lesion. This requires first learning whether the tumor stem cells in culture express LDL receptors, and next establishing a selection or screening procedure to identify receptor-deficient mutants in mutagenized cell cultures. The results show that the teratocarcinoma cells do in fact have specific high-affinity LDL receptors which are similar to those reported for fibroblasts and the parenchymal cells of specialized tissues and different from those of phagocytic cells. Sterols suppressed the otherwise efficient binding, internalization, and degradation of LDL ((125)I-labeled) by the cells. Acetylation of LDL blocked the binding. Only LDL and not high density lipoprotein (HDL) was bound. After LDL uptake and degradation, the liberated cholesterol led, as expected, to increased cholesteryl ester formation; it also suppressed activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase [HMG CoA reductase; mevalonate: NADP(+) oxidoreductase (CoA-acylating), EC 1.1.1.34], the rate-limiting step in cholesterol biosynthesis. Cells with LDL receptors were readily visualized by administering a fluorescent derivative of LDL; in the fluorescence microscope, labeling was seen in all cells. Cells with experimentally depressed receptors, yielding little fluorescence, were separable from those with normal fluorescence in the fluorescence-activated cell sorter. Thus, two methods for isolating receptor-deficient cells from mutagenized cultures are now available, either by visual recognition of low-fluorescing or nonfluorescing colonies in culture plates or by electronic cell sorting. Such mutants in an appropriate line of teratocarcinoma cells can then be passaged into blastocysts for full somatic tissue differentiation and germ-line development into mice.", "contents": "Demonstration of low density lipoprotein receptors in mouse teratocarcinoma stem cells and description of a method for producing receptor-deficient mutant mice. Familial hypercholesterolemia, a widespread human genetic disorder implicated in vascular and coronary disease, has had no laboratory animal counterpart that would enable the pathogenesis to be analyzed and drugs to be tested in vivo. The primary lesion in some patients is known to occur in the cells' initial handling of the major cholesterol-carrying lipoprotein of plasma. It entails a deficiency in the specific cell surface receptor that binds low density lipoprotein (LDL), with a consequent alteration in the control of cholesterol metabolism. The present study was undertaken to devise a practical scheme for producing, from developmentally versatile mouse teratocarcinoma stem cells, whole-animal models with a comparable genetic lesion. This requires first learning whether the tumor stem cells in culture express LDL receptors, and next establishing a selection or screening procedure to identify receptor-deficient mutants in mutagenized cell cultures. The results show that the teratocarcinoma cells do in fact have specific high-affinity LDL receptors which are similar to those reported for fibroblasts and the parenchymal cells of specialized tissues and different from those of phagocytic cells. Sterols suppressed the otherwise efficient binding, internalization, and degradation of LDL ((125)I-labeled) by the cells. Acetylation of LDL blocked the binding. Only LDL and not high density lipoprotein (HDL) was bound. After LDL uptake and degradation, the liberated cholesterol led, as expected, to increased cholesteryl ester formation; it also suppressed activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase [HMG CoA reductase; mevalonate: NADP(+) oxidoreductase (CoA-acylating), EC 1.1.1.34], the rate-limiting step in cholesterol biosynthesis. Cells with LDL receptors were readily visualized by administering a fluorescent derivative of LDL; in the fluorescence microscope, labeling was seen in all cells. Cells with experimentally depressed receptors, yielding little fluorescence, were separable from those with normal fluorescence in the fluorescence-activated cell sorter. Thus, two methods for isolating receptor-deficient cells from mutagenized cultures are now available, either by visual recognition of low-fluorescing or nonfluorescing colonies in culture plates or by electronic cell sorting. Such mutants in an appropriate line of teratocarcinoma cells can then be passaged into blastocysts for full somatic tissue differentiation and germ-line development into mice."}
{"id": "PMID:223162", "title": "Simian virus 40 recombinants are produced at high frequency during infection with genetically mixed oligomeric DNA.", "content": "Classical approaches to analysis of mitotic recombination by use of simian virus 40 (SV40) are limited in usefulness because of low frequencies of recombination. To bypass the apparent rate-limiting step in normal SV40 recombination, oligomeric SV40 was constructed in vitro by ligation of mixtures of pairs of linear DNAs carrying genetically distinct temperature-sensitive mutations. Cultured monkey cells infected with the unfractionated ligation products yielded frequencies of nonparental recombinant progeny that were increased up to 500-fold relative to cells infected with a mixture of the untreated circular molecules. Pairwise crosses were performed with tsB4, tsB8, and tsBC11 DNAs, using unfractionated oligomers constructed from linear molecules cleaved by EcoRI or BamHI. In each cross the fraction of progeny with nonparental genotypes was roughly proportional to the physical distances between the mutant sites. These results suggest a random, rather than site-specific, conversion of oligomers to monomers. Somewhat surprisingly, nonligated mixtures of linear tsB4 and tsB8 DNAs, created by EcoRI digestion, produced a 40-t to 100-fold increase in the frequency of nonparental progeny. These results indicate that intermolecular associations must occur with fairly high efficiency between these linear molecules.", "contents": "Simian virus 40 recombinants are produced at high frequency during infection with genetically mixed oligomeric DNA. Classical approaches to analysis of mitotic recombination by use of simian virus 40 (SV40) are limited in usefulness because of low frequencies of recombination. To bypass the apparent rate-limiting step in normal SV40 recombination, oligomeric SV40 was constructed in vitro by ligation of mixtures of pairs of linear DNAs carrying genetically distinct temperature-sensitive mutations. Cultured monkey cells infected with the unfractionated ligation products yielded frequencies of nonparental recombinant progeny that were increased up to 500-fold relative to cells infected with a mixture of the untreated circular molecules. Pairwise crosses were performed with tsB4, tsB8, and tsBC11 DNAs, using unfractionated oligomers constructed from linear molecules cleaved by EcoRI or BamHI. In each cross the fraction of progeny with nonparental genotypes was roughly proportional to the physical distances between the mutant sites. These results suggest a random, rather than site-specific, conversion of oligomers to monomers. Somewhat surprisingly, nonligated mixtures of linear tsB4 and tsB8 DNAs, created by EcoRI digestion, produced a 40-t to 100-fold increase in the frequency of nonparental progeny. These results indicate that intermolecular associations must occur with fairly high efficiency between these linear molecules."}
{"id": "PMID:223163", "title": "(E)-5-(2-Bromovinyl)-2'-deoxyuridine: a potent and selective anti-herpes agent.", "content": "Of a series of five newly synthesized 2'-deoxyuridine derivatives, including 5-vinyl-dUrd, 5-ethynyl-dUrd, 5-(1-chlorovinyl)-dUrd, (E)-5-(2-bromovinyl)-dUrd, and (E)-5-(2-iodovinyl)-dUrd, the last two compounds were found to exert a marked inhibitory effect on the replication of herpes simplex virus type 1 [ID50 (mean inhibitory dose), 0.004-0.02 microgram/ml]. Both (E)-5-(2-bromovinyl)-dUrd and (E)-5-(2-iodovinyl)-dUrd were highly selective in their anti-herpes activity in that they did not affect the growth or metabolism of the host (primary rabbit kidney) cells unless drug concentrations were used that were 5,000- to 10,000-fold greater than those required to inhibit virus multiplication. In this sense (E)-5-(2-bromovinyl)-dUrd and (E)-5-(2-iodovinyl)-dUrd proved more selective in their activity against herpes simplex virus type 1 than all other anti-herpes compounds that have been described so far. In animal model systems (namely, cutaneous herpes infections of athymic nude mice), (E)-5-(2-bromovinyl)-dUrd suppressed the development of herpetic skin lesions and mortality therewith associated, whether the compound was administered topically or systemically. Under the same conditions, the standard anti-herpes drug 5-iodo-dUrd (Idoxuridine) offered little, if any, protection. Although the precise mechanism of action of (E)-5-(2-bromovinyl)-dUrd and (E)-5-(2-iodovinyl)-dUrd remains to be established, preliminary findings indicate that they do not specifically act at the thymidylate synthetase step.", "contents": "(E)-5-(2-Bromovinyl)-2'-deoxyuridine: a potent and selective anti-herpes agent. Of a series of five newly synthesized 2'-deoxyuridine derivatives, including 5-vinyl-dUrd, 5-ethynyl-dUrd, 5-(1-chlorovinyl)-dUrd, (E)-5-(2-bromovinyl)-dUrd, and (E)-5-(2-iodovinyl)-dUrd, the last two compounds were found to exert a marked inhibitory effect on the replication of herpes simplex virus type 1 [ID50 (mean inhibitory dose), 0.004-0.02 microgram/ml]. Both (E)-5-(2-bromovinyl)-dUrd and (E)-5-(2-iodovinyl)-dUrd were highly selective in their anti-herpes activity in that they did not affect the growth or metabolism of the host (primary rabbit kidney) cells unless drug concentrations were used that were 5,000- to 10,000-fold greater than those required to inhibit virus multiplication. In this sense (E)-5-(2-bromovinyl)-dUrd and (E)-5-(2-iodovinyl)-dUrd proved more selective in their activity against herpes simplex virus type 1 than all other anti-herpes compounds that have been described so far. In animal model systems (namely, cutaneous herpes infections of athymic nude mice), (E)-5-(2-bromovinyl)-dUrd suppressed the development of herpetic skin lesions and mortality therewith associated, whether the compound was administered topically or systemically. Under the same conditions, the standard anti-herpes drug 5-iodo-dUrd (Idoxuridine) offered little, if any, protection. Although the precise mechanism of action of (E)-5-(2-bromovinyl)-dUrd and (E)-5-(2-iodovinyl)-dUrd remains to be established, preliminary findings indicate that they do not specifically act at the thymidylate synthetase step."}
{"id": "PMID:223164", "title": "Murine cytomegalovirus infects spermatogenic cells.", "content": "Murine cytomegalovirus replicated in reproductive tissue of male mice infected with the virus. We examined three strains of mice latently infected by injection at birth with 100 plaque-forming units of the virus. As adults, these mice contained within their testes 4--6 viral genomic equivalents per 100 cells, as tested by hybridization between mouse DNA and cytomegalovirus DNA. Acutely infected male adult CBA mice homozygous for the nude gene (athymic: nude/nude) produced infectious virus in their testes, the amounts of which varied according to the animal's age at the time of infection. Heterozygous (nude/+) litter mates contained significantly less virus than nude/nude mice. At the peak of virus replication hybridization between virus DNA and mouse DNA indicated the presence of 3.3 viral genome equivalents per testicular cell. Both in situ hybridization studies and phenol emulsion reassociation of virus DNA to DNA from purified spermatozoa localized this viral DNA to immature and mature sperm cells. Hence, murine cytomegalovirus can be harbored in testes during both acute and latent infections and can replicate in male germ-line cells.", "contents": "Murine cytomegalovirus infects spermatogenic cells. Murine cytomegalovirus replicated in reproductive tissue of male mice infected with the virus. We examined three strains of mice latently infected by injection at birth with 100 plaque-forming units of the virus. As adults, these mice contained within their testes 4--6 viral genomic equivalents per 100 cells, as tested by hybridization between mouse DNA and cytomegalovirus DNA. Acutely infected male adult CBA mice homozygous for the nude gene (athymic: nude/nude) produced infectious virus in their testes, the amounts of which varied according to the animal's age at the time of infection. Heterozygous (nude/+) litter mates contained significantly less virus than nude/nude mice. At the peak of virus replication hybridization between virus DNA and mouse DNA indicated the presence of 3.3 viral genome equivalents per testicular cell. Both in situ hybridization studies and phenol emulsion reassociation of virus DNA to DNA from purified spermatozoa localized this viral DNA to immature and mature sperm cells. Hence, murine cytomegalovirus can be harbored in testes during both acute and latent infections and can replicate in male germ-line cells."}
{"id": "PMID:223165", "title": "Virus-specified protease in poliovirus-infected HeLa cells.", "content": "Previous studies have shown that primary cleavages in nascent picornavirus precursors are accomplished by cellular proteases. This study has characterized the enzyme in infected cells that produces the capsid polypeptides by secondary cleavages of viral precursors. The kinetics of the production of protease activity correlate with the time course of virus protein synthesis, and the new enzyme has characteristic pH and temperature optima. Guanidine and cycloheximide, which are inhibitors of virus RNA and protein synthesis, prevent production of the protease. As determined by introduction of amino acid analogs into the protease or inhibition by a leucyl chloromethyl ketone, the enzyme is synthesized at a time of infection when host cell proteins are not produced, and the enzyme copurified with a 40,000-dalton virus polypeptide present in the cytoplasm of infected cells. Wild-type levels of protease activity are produced by viral mutants that are defective in coat protein synthesis. The conclusion is that a non-structural poliovirus gene product participates in protein cleavages that produce the viral coat proteins.", "contents": "Virus-specified protease in poliovirus-infected HeLa cells. Previous studies have shown that primary cleavages in nascent picornavirus precursors are accomplished by cellular proteases. This study has characterized the enzyme in infected cells that produces the capsid polypeptides by secondary cleavages of viral precursors. The kinetics of the production of protease activity correlate with the time course of virus protein synthesis, and the new enzyme has characteristic pH and temperature optima. Guanidine and cycloheximide, which are inhibitors of virus RNA and protein synthesis, prevent production of the protease. As determined by introduction of amino acid analogs into the protease or inhibition by a leucyl chloromethyl ketone, the enzyme is synthesized at a time of infection when host cell proteins are not produced, and the enzyme copurified with a 40,000-dalton virus polypeptide present in the cytoplasm of infected cells. Wild-type levels of protease activity are produced by viral mutants that are defective in coat protein synthesis. The conclusion is that a non-structural poliovirus gene product participates in protein cleavages that produce the viral coat proteins."}
{"id": "PMID:223166", "title": "Amino-terminal sequence of bovine leukemia virus major internal protein: homology with mammalian type C virus p30 structural proteins.", "content": "The amino acid composition, the COOH-terminal amino acid, and the NH2-terminal amino acid sequence of the first 55 residues of the major internal structural protein, p24, of bovine leukemia virus (BLV) were determined. The compositional data and the results of end-group analysis revealed that, although BLV p24 is chemically distinct, it more closely resembles the p30 structural proteins than the other gag gene products of mammalian retroviruses. It was found that BLV p24 shares the common NH2-terminal proline and COOH-terminal leucine but lacks the common prolylleucylarginine tripeptide and the larger conserved region found near the NH2 terminus of all mammalian type C viral p30s. Alignment of the amino acid sequence of BLV p24 with the previously determined sequence of feline leukemia virus p27 revealed a statistically significant sequence homology. A more distant relationship was found between BLV p24 and other mammalian p30s. The finding of a definite sequence homology between BLV p24 and mammalian type C virus p30s clearly establishes the origin of these contemporary viral proteins from common progenitor genes.", "contents": "Amino-terminal sequence of bovine leukemia virus major internal protein: homology with mammalian type C virus p30 structural proteins. The amino acid composition, the COOH-terminal amino acid, and the NH2-terminal amino acid sequence of the first 55 residues of the major internal structural protein, p24, of bovine leukemia virus (BLV) were determined. The compositional data and the results of end-group analysis revealed that, although BLV p24 is chemically distinct, it more closely resembles the p30 structural proteins than the other gag gene products of mammalian retroviruses. It was found that BLV p24 shares the common NH2-terminal proline and COOH-terminal leucine but lacks the common prolylleucylarginine tripeptide and the larger conserved region found near the NH2 terminus of all mammalian type C viral p30s. Alignment of the amino acid sequence of BLV p24 with the previously determined sequence of feline leukemia virus p27 revealed a statistically significant sequence homology. A more distant relationship was found between BLV p24 and other mammalian p30s. The finding of a definite sequence homology between BLV p24 and mammalian type C virus p30s clearly establishes the origin of these contemporary viral proteins from common progenitor genes."}
{"id": "PMID:223167", "title": "Recombination between the defective component of an acute leukemia virus and Rous associated virus O, an endogenous virus of chickens.", "content": "The ability of the defective acute leukemia virus of chickens, MC-29, to participate in recombination was investigated by testing the ability of the MC-29 genome to donate sequences to its helper virus. The endogenous virus Rous associated virus O (RAV-O) was used as a helper for MC-29, and its genome was compared by fingerprinting to that of the original RAV-O. In three separate isolates, it was found that the RAV-O used as helper for MC-29 had acquired new sequences near the 3' and 5' ends of its genome. The new 3' proximal sequences resembled the C region found in exogenous but not endogenous avian oncoviruses, and it probably imparted a higher growth rate to the recombinant as compared to RAV-O. One isolate also showed recombination within the env gene. Because we could exclude the possibility that the recombination was with host cell information or with the original helper of MC-29, we conclude that the acquired sequences were derived from the MC-29 genome, and therefore this replication defective virus is not defective in recombination.", "contents": "Recombination between the defective component of an acute leukemia virus and Rous associated virus O, an endogenous virus of chickens. The ability of the defective acute leukemia virus of chickens, MC-29, to participate in recombination was investigated by testing the ability of the MC-29 genome to donate sequences to its helper virus. The endogenous virus Rous associated virus O (RAV-O) was used as a helper for MC-29, and its genome was compared by fingerprinting to that of the original RAV-O. In three separate isolates, it was found that the RAV-O used as helper for MC-29 had acquired new sequences near the 3' and 5' ends of its genome. The new 3' proximal sequences resembled the C region found in exogenous but not endogenous avian oncoviruses, and it probably imparted a higher growth rate to the recombinant as compared to RAV-O. One isolate also showed recombination within the env gene. Because we could exclude the possibility that the recombination was with host cell information or with the original helper of MC-29, we conclude that the acquired sequences were derived from the MC-29 genome, and therefore this replication defective virus is not defective in recombination."}
{"id": "PMID:223168", "title": "Evidence for internalization of the recognition site of beta-adrenergic receptors during receptor subsensitivity induced by (-)-isoproterenol.", "content": "In the supernatant (30,000 x g) of frog erythrocyte homogenates, by using gel filtration we detected a protein that could bind [(3)H]dihydroalprenolol ([(3)H]DHA) with high affinity. This binding was greatly enhanced when the erythrocytes were preincubated with (-)-isoproterenol. After various periods of incubation with (-)-isoproterenol, the extent of the increase in the density of [(3)H]DHA binding sites in the cytosol was paralleled by a proportional decrease in the number of [(3)H]DHA binding sites in the corresponding pellet; both events peaked after 2-3 hr of incubation with (-)-isoproterenol. The K(a) of the (-)-isoproterenol-induced increase in [(3)H]DHA binding in cytosol and the decrease in this binding in the membrane ranged between 60 and 90 nM. The changes in the cytosol and particulate [(3)H]DHA binding sites were independent of RNA and protein synthesis. The increase in cytosol binding elicited by (-)-isoproterenol was blocked by exposure of the cells to (-)-alprenolol which per se failed to change the cytosol binding of [(3)H]DHA. Scatchard analysis revealed that the enhanced [(3)H]DHA binding to cytosol material was due to a 4-fold increase in the B(max) with little or no change in K(d) ( approximately 9 nM). Binding displacement data show that these soluble [(3)H]DHA binding sites resemble the surface membrane recognition sites. Moreover, the ability of various beta-adrenergic agents to increase [(3)H]DHA binding to cytosol after they were incubated with frog erythrocytes paralleled their affinity for membrane-bound beta receptors. These findings support the view that the beta-adrenergic receptor desensitization caused by prolonged exposure to (-)-isoproterenol is due, at least in part, to an internalization of the recognition site of beta-adrenergic receptors.", "contents": "Evidence for internalization of the recognition site of beta-adrenergic receptors during receptor subsensitivity induced by (-)-isoproterenol. In the supernatant (30,000 x g) of frog erythrocyte homogenates, by using gel filtration we detected a protein that could bind [(3)H]dihydroalprenolol ([(3)H]DHA) with high affinity. This binding was greatly enhanced when the erythrocytes were preincubated with (-)-isoproterenol. After various periods of incubation with (-)-isoproterenol, the extent of the increase in the density of [(3)H]DHA binding sites in the cytosol was paralleled by a proportional decrease in the number of [(3)H]DHA binding sites in the corresponding pellet; both events peaked after 2-3 hr of incubation with (-)-isoproterenol. The K(a) of the (-)-isoproterenol-induced increase in [(3)H]DHA binding in cytosol and the decrease in this binding in the membrane ranged between 60 and 90 nM. The changes in the cytosol and particulate [(3)H]DHA binding sites were independent of RNA and protein synthesis. The increase in cytosol binding elicited by (-)-isoproterenol was blocked by exposure of the cells to (-)-alprenolol which per se failed to change the cytosol binding of [(3)H]DHA. Scatchard analysis revealed that the enhanced [(3)H]DHA binding to cytosol material was due to a 4-fold increase in the B(max) with little or no change in K(d) ( approximately 9 nM). Binding displacement data show that these soluble [(3)H]DHA binding sites resemble the surface membrane recognition sites. Moreover, the ability of various beta-adrenergic agents to increase [(3)H]DHA binding to cytosol after they were incubated with frog erythrocytes paralleled their affinity for membrane-bound beta receptors. These findings support the view that the beta-adrenergic receptor desensitization caused by prolonged exposure to (-)-isoproterenol is due, at least in part, to an internalization of the recognition site of beta-adrenergic receptors."}
{"id": "PMID:223173", "title": "Spontaneous vs. naloxone-induced abstinence in dependent rats self-administering L-alpha-acetylmethadol (LAAM) or morphine.", "content": "Rats maintained dependence by the self-administration of LAAM or morphine. Following the substitution of saline for LAAM, REM sleep was not disrupted, and the frequency of lever pressing for saline self-injections peaked at about 24 hr. In contrast, following the substitution of saline for morphine, REM sleep was suppressed for 24 hr while the frequency of lever pressing for saline self-injections peaked within 8 hr. When abstinence was induced by hourly iv naloxone injections, REM sleep occurrences were suppressed to a similar degree and for similar durations during naloxone-induced abstinence from both morphine and LAAM. These results suggest that the level of physical dependence maintained during self-administration of LAAM and morphine was similar. The relatively mild abstinence syndrome that was seen during saline substitution in LAAM-dependent rats was most likely related to the long plasma half-lives of the pharmacologically active N-demethylated metabolites of LAAM.", "contents": "Spontaneous vs. naloxone-induced abstinence in dependent rats self-administering L-alpha-acetylmethadol (LAAM) or morphine. Rats maintained dependence by the self-administration of LAAM or morphine. Following the substitution of saline for LAAM, REM sleep was not disrupted, and the frequency of lever pressing for saline self-injections peaked at about 24 hr. In contrast, following the substitution of saline for morphine, REM sleep was suppressed for 24 hr while the frequency of lever pressing for saline self-injections peaked within 8 hr. When abstinence was induced by hourly iv naloxone injections, REM sleep occurrences were suppressed to a similar degree and for similar durations during naloxone-induced abstinence from both morphine and LAAM. These results suggest that the level of physical dependence maintained during self-administration of LAAM and morphine was similar. The relatively mild abstinence syndrome that was seen during saline substitution in LAAM-dependent rats was most likely related to the long plasma half-lives of the pharmacologically active N-demethylated metabolites of LAAM."}
{"id": "PMID:223174", "title": "Influence of opioids on central thermoregulatory mechanisms.", "content": "Of the effects of morphine and endogenous opioid peptides on thermoregulation, the one which is most likely to be of physiologic significance is hyperthermia. This increase in body temperature is the result of coordinated changes in both physiological and behavioral thermoregulatory activities and, like fever, reflects an increase in the level about which body temperature is regulated. Morphine, endogenous opioid peptides and other opioids such as pentazocine all cause hyperthermia, but the considerable variation in the dose of naloxone required to antagonize the different agonists indicates that more than one type of opiate receptor is involved in these pharmacologic responses. The minimal effect of naloxone and naltrexone on normal body temperature and on pyrogen-induced fever indicates that endogenous opioid peptides are unlikely to act physiologically via stimulation of receptors specifically sensitive to morphine. However, methionine-enkephalin is less readily antagonized by naloxone and could have a physiologic role in thermoregulation through stimulation of another type of opiate receptor.", "contents": "Influence of opioids on central thermoregulatory mechanisms. Of the effects of morphine and endogenous opioid peptides on thermoregulation, the one which is most likely to be of physiologic significance is hyperthermia. This increase in body temperature is the result of coordinated changes in both physiological and behavioral thermoregulatory activities and, like fever, reflects an increase in the level about which body temperature is regulated. Morphine, endogenous opioid peptides and other opioids such as pentazocine all cause hyperthermia, but the considerable variation in the dose of naloxone required to antagonize the different agonists indicates that more than one type of opiate receptor is involved in these pharmacologic responses. The minimal effect of naloxone and naltrexone on normal body temperature and on pyrogen-induced fever indicates that endogenous opioid peptides are unlikely to act physiologically via stimulation of receptors specifically sensitive to morphine. However, methionine-enkephalin is less readily antagonized by naloxone and could have a physiologic role in thermoregulation through stimulation of another type of opiate receptor."}
{"id": "PMID:223177", "title": "Reflections on the topics: EEG frequency bands and regulation of vigilance.", "content": "A critical analysis of quantitative pharmaco-electroencephalography begins with parametrization into variables. The determination of frequency bands according to clinical criteria should be reconsidered. Alternatives may be the determination of factor scores or the definition of frequency bands based on factor analysis. If the latter procedure is used, the clinical alpha-band is subdivided into a lower (alpha 1F = 8,5-10.5 HZ) and an upper (alpha 2F = 10.5-12.5 HZ) part. Furthermore parts of the clinical theta-band (and the delta-band are combined into the delta F-band (1.5-6.0 HZ), for awake healthy volunteers with an occipital alpha-rhythm. Existing concepts of vigilance for the awake stages are not contradictory to the following observations: the factor structure of EEG relative power spectrum variables shows a negative correlation of slow alpha-frequencies with those in the delta F- and beta 3F-band. There is also a negative correlation between slow and fast alpha-wave relative power values.", "contents": "Reflections on the topics: EEG frequency bands and regulation of vigilance. A critical analysis of quantitative pharmaco-electroencephalography begins with parametrization into variables. The determination of frequency bands according to clinical criteria should be reconsidered. Alternatives may be the determination of factor scores or the definition of frequency bands based on factor analysis. If the latter procedure is used, the clinical alpha-band is subdivided into a lower (alpha 1F = 8,5-10.5 HZ) and an upper (alpha 2F = 10.5-12.5 HZ) part. Furthermore parts of the clinical theta-band (and the delta-band are combined into the delta F-band (1.5-6.0 HZ), for awake healthy volunteers with an occipital alpha-rhythm. Existing concepts of vigilance for the awake stages are not contradictory to the following observations: the factor structure of EEG relative power spectrum variables shows a negative correlation of slow alpha-frequencies with those in the delta F- and beta 3F-band. There is also a negative correlation between slow and fast alpha-wave relative power values."}
{"id": "PMID:223178", "title": "The neurology of spinal pain.", "content": "The neuroanatomical and physiological aspects of pain derived from the spine are reviewed. An explanation is presented of the influence of passive movement as it relates to the interaction of the mechanoreceptor afferent nerves' modulation of nociceptive input.", "contents": "The neurology of spinal pain. The neuroanatomical and physiological aspects of pain derived from the spine are reviewed. An explanation is presented of the influence of passive movement as it relates to the interaction of the mechanoreceptor afferent nerves' modulation of nociceptive input."}
{"id": "PMID:223182", "title": "The effect of dibutyryl cyclic AMP on cultivated glial cells from corpus callosum of 30-day-old rats.", "content": "1) Fragments of corpus callosum of 30-day-old rats were cultivated in Rose chambers. Mature astrocytes and predominantly differentiated oligodendroglial cells are present in the corpus callosum of rats at this age. 2) In vitro, astrocytes dedifferentiated into epithelial--like flattened cells, which highly adhered to the surface. Cells exhibited signs of phagocytosis, and their ultrastructure differed from differentiated cells, especially by the absence of microtubules and microfilaments. 3) After dibutyryl cyclic AMP (db-c-AMP) application, epithelial--like cells became rounded and multipolar. Cells were less liable to adhere to the surface. Bundles of microfilaments and microtubules appeared in cell perikarya and their processes. 3--4 hour after application, the morphological changes were well developed and disappeared after 24--48 hours. 4) It is being suggested that the increased intracellular concentration of db-c-AMP induced the formation of microfilamentous structures. The formation of the cyto-skeleton has a direct influence on the shape of cells and appearance of processes and cell adhesivity. 5) These results have demonstrated the high structural plasticity of mature astrocytes, their dedifferentiation in vitro and convertion into mature cells after db-c-AMP application.", "contents": "The effect of dibutyryl cyclic AMP on cultivated glial cells from corpus callosum of 30-day-old rats. 1) Fragments of corpus callosum of 30-day-old rats were cultivated in Rose chambers. Mature astrocytes and predominantly differentiated oligodendroglial cells are present in the corpus callosum of rats at this age. 2) In vitro, astrocytes dedifferentiated into epithelial--like flattened cells, which highly adhered to the surface. Cells exhibited signs of phagocytosis, and their ultrastructure differed from differentiated cells, especially by the absence of microtubules and microfilaments. 3) After dibutyryl cyclic AMP (db-c-AMP) application, epithelial--like cells became rounded and multipolar. Cells were less liable to adhere to the surface. Bundles of microfilaments and microtubules appeared in cell perikarya and their processes. 3--4 hour after application, the morphological changes were well developed and disappeared after 24--48 hours. 4) It is being suggested that the increased intracellular concentration of db-c-AMP induced the formation of microfilamentous structures. The formation of the cyto-skeleton has a direct influence on the shape of cells and appearance of processes and cell adhesivity. 5) These results have demonstrated the high structural plasticity of mature astrocytes, their dedifferentiation in vitro and convertion into mature cells after db-c-AMP application."}
{"id": "PMID:223183", "title": "Effect of altitude hypoxia on ATPase activity in the brain of rats of different ages.", "content": "In experiments on 5-day-old and adult rats of both sexes, the authors investigated Na+--K+-stimulated and Mg2+-dependent ATPase activity in the cerebral cortex, subcortical formations and the medulla oblongata. They studied the effect of 20 min acute altitude hypoxia corresponding to either 7,000 or 9,000 m, in a thermostable chamber (30 degrees C). ATPase activity was found to increase during ontogenesis -- this being the greatest in cortical tissue and the least in the medulla oblongata. Hypoxia corresponding to 7,000 m altitude significantly depressed total ATPase activity in 5-day-old rats, but significantly stimulated it in adult animals. Changes in Na+--K+-stimulated ATPase activity played the major role in these changes. Hypoxia corresponding to 9,000 m altitude likewise depressed total ATPase activity in 5-day-old rats and to practically the same extent as moderate hypoxia (7,000 m). In adult rats, marked hypoxia (9,000 m) significantly reduced only Mg2+-dependent ATPase activity. Mg2+ activity rose during ontogenesis to a lesser degree than Na+--K+-stimulated ATPase and the reciprocal ratio of these ATPase and the reciprocal ratio of these ATPase activities, in the given parts of the brain, fell progressively in adult animals to values close to 1.", "contents": "Effect of altitude hypoxia on ATPase activity in the brain of rats of different ages. In experiments on 5-day-old and adult rats of both sexes, the authors investigated Na+--K+-stimulated and Mg2+-dependent ATPase activity in the cerebral cortex, subcortical formations and the medulla oblongata. They studied the effect of 20 min acute altitude hypoxia corresponding to either 7,000 or 9,000 m, in a thermostable chamber (30 degrees C). ATPase activity was found to increase during ontogenesis -- this being the greatest in cortical tissue and the least in the medulla oblongata. Hypoxia corresponding to 7,000 m altitude significantly depressed total ATPase activity in 5-day-old rats, but significantly stimulated it in adult animals. Changes in Na+--K+-stimulated ATPase activity played the major role in these changes. Hypoxia corresponding to 9,000 m altitude likewise depressed total ATPase activity in 5-day-old rats and to practically the same extent as moderate hypoxia (7,000 m). In adult rats, marked hypoxia (9,000 m) significantly reduced only Mg2+-dependent ATPase activity. Mg2+ activity rose during ontogenesis to a lesser degree than Na+--K+-stimulated ATPase and the reciprocal ratio of these ATPase and the reciprocal ratio of these ATPase activities, in the given parts of the brain, fell progressively in adult animals to values close to 1."}
{"id": "PMID:223186", "title": "Effects of loxapine on the sleep of chronic schizophrenics.", "content": "The sleep patterns of four male chronic schizophrenic patients were monitored throughout the various phases of a 1-year therapeutic trial with loxapine succinate, a newly developed neuroleptic. Compared with the initial drug-free baseline, the early drug period was characterized by an increase in REM percentage, REM density, and REM activity. During the drug maintenance period, the increase in REM phasic events was accompanied by an increase in total sleep. Severe insomnia was noted during the initial period of drug withdrawal. The absence of time lag between changes in drug administration schedule and the associated alterations in sleep patterns was in contrast with the time latency of the therapeutic response. This neuroleptic on sleep and on psychopathology are mediated by different mechanisms.", "contents": "Effects of loxapine on the sleep of chronic schizophrenics. The sleep patterns of four male chronic schizophrenic patients were monitored throughout the various phases of a 1-year therapeutic trial with loxapine succinate, a newly developed neuroleptic. Compared with the initial drug-free baseline, the early drug period was characterized by an increase in REM percentage, REM density, and REM activity. During the drug maintenance period, the increase in REM phasic events was accompanied by an increase in total sleep. Severe insomnia was noted during the initial period of drug withdrawal. The absence of time lag between changes in drug administration schedule and the associated alterations in sleep patterns was in contrast with the time latency of the therapeutic response. This neuroleptic on sleep and on psychopathology are mediated by different mechanisms."}
{"id": "PMID:223192", "title": "Morphologic-radiographic correlations of the pancreas.", "content": "Numerous noninvasive and invasive imaging modalities are available for the study of pancreatic disease. Disappointingly, the radiographic demonstration of a pancreatic neoplasm is more successful than the treatment of the disease. The proximity of large vascular structures to the pancreas makes its study technically difficult and explains why vascular invasion is readily caused by dispersion of pancreatic secretions (as seen in pancreatitis) or by neoplastic infiltration. The latter heralds nonresectability. Needle biopsy under fluoroscopic or echographic control appears to be gaining popularity as a simple, sensitive and specific method for establishing the diagnosis of pancreatic malignancy. Angiography has its highest yield in the diagnosis of islet cell tumors because they are generally hypervascular. This technique has been complemented by selective catheterization of pancreatic veins followed by hormone bioassay determinations.", "contents": "Morphologic-radiographic correlations of the pancreas. Numerous noninvasive and invasive imaging modalities are available for the study of pancreatic disease. Disappointingly, the radiographic demonstration of a pancreatic neoplasm is more successful than the treatment of the disease. The proximity of large vascular structures to the pancreas makes its study technically difficult and explains why vascular invasion is readily caused by dispersion of pancreatic secretions (as seen in pancreatitis) or by neoplastic infiltration. The latter heralds nonresectability. Needle biopsy under fluoroscopic or echographic control appears to be gaining popularity as a simple, sensitive and specific method for establishing the diagnosis of pancreatic malignancy. Angiography has its highest yield in the diagnosis of islet cell tumors because they are generally hypervascular. This technique has been complemented by selective catheterization of pancreatic veins followed by hormone bioassay determinations."}
{"id": "PMID:223194", "title": "Congenital mesoblastic nephroma.", "content": "Congenital mesoblastic nephromas are infiltrating tumors that can contain cystic spaces lined with epithelium similar to that of dysplastic tubules and glomeruli. Urographic contrast material may enter these cystic spaces and suggest the diagnosis.", "contents": "Congenital mesoblastic nephroma. Congenital mesoblastic nephromas are infiltrating tumors that can contain cystic spaces lined with epithelium similar to that of dysplastic tubules and glomeruli. Urographic contrast material may enter these cystic spaces and suggest the diagnosis."}
{"id": "PMID:223195", "title": "Abdominal pansonography in the evaluation of renal cancer.", "content": "Abdominal pansonography was performed in 34 patients after solid renal tumors were diagnosed. Included were evaluation of the inferior vena cava (IVC), the liver, and the retroperitoneal area. Additional findings including hepatic metastases, IVC extension of tumor, and retroperitoneal nodal masses were discovered in 14 patients. The role of pansonography as a noninvasive adjunctive diagnostic tool for more complete staging and treatment planning of renal cancer is discussed.", "contents": "Abdominal pansonography in the evaluation of renal cancer. Abdominal pansonography was performed in 34 patients after solid renal tumors were diagnosed. Included were evaluation of the inferior vena cava (IVC), the liver, and the retroperitoneal area. Additional findings including hepatic metastases, IVC extension of tumor, and retroperitoneal nodal masses were discovered in 14 patients. The role of pansonography as a noninvasive adjunctive diagnostic tool for more complete staging and treatment planning of renal cancer is discussed."}
{"id": "PMID:223196", "title": "Response to thoracic radiotherapy in patients with small cell carcinoma of the lung after failure of combination chemotherapy.", "content": "Chest radiotherapy was given to 23 patients with small cell carcinoma of the lung after development of progressive intrathoracic tumor on chemotherapeutic regimens. Treatment schedules were variable, with a median dose of 3,200 rad (32 Gy) in 10 fractions. Objective tumor regression within the radiation portal was observed in 12 patients (52%). Only 3/12 responders did not develop clinically detectable local tumor recurrence before death. Actuarial median time to local tumor progression was 2.5 months in responding and 3.5 months in nonresponding patients. Relapse of intrathoracic small cell carcinoma despite combination chemotherapy was not effectively treated by chest irradiation in the doses utilized. If sustained local palliation is required in this population, higher doses of radiation should be considered.", "contents": "Response to thoracic radiotherapy in patients with small cell carcinoma of the lung after failure of combination chemotherapy. Chest radiotherapy was given to 23 patients with small cell carcinoma of the lung after development of progressive intrathoracic tumor on chemotherapeutic regimens. Treatment schedules were variable, with a median dose of 3,200 rad (32 Gy) in 10 fractions. Objective tumor regression within the radiation portal was observed in 12 patients (52%). Only 3/12 responders did not develop clinically detectable local tumor recurrence before death. Actuarial median time to local tumor progression was 2.5 months in responding and 3.5 months in nonresponding patients. Relapse of intrathoracic small cell carcinoma despite combination chemotherapy was not effectively treated by chest irradiation in the doses utilized. If sustained local palliation is required in this population, higher doses of radiation should be considered."}
{"id": "PMID:223197", "title": "Prognostic significance of lesion size for glioblastoma multiforme.", "content": "From March 1974 to December 1976, 56 patients with glioblastoma multiforme had precraniotomy computed tomography (CT) scans from which the lesion size was determined by measuring the cross-sectional area. Thirty-two patients underwent surgery followed by irradiation, and 24 had surgery followed by irradiation and chemotherapy. There was no difference in survival between the 16 patients with small lesions and the 16 patients with large lesions in the surgery plus radiation alone group, nor in the 16 patients with small and 8 patients with large lesions in the surgery, radiation and chemotherapy group. Minimum follow-up was one year. Other possible prognostic factors including age, tumor grade, radiation dose, and performance status were comparable for each subgroup. Lesion size in glioblastoma multiforme appears unrelated to prognosis.", "contents": "Prognostic significance of lesion size for glioblastoma multiforme. From March 1974 to December 1976, 56 patients with glioblastoma multiforme had precraniotomy computed tomography (CT) scans from which the lesion size was determined by measuring the cross-sectional area. Thirty-two patients underwent surgery followed by irradiation, and 24 had surgery followed by irradiation and chemotherapy. There was no difference in survival between the 16 patients with small lesions and the 16 patients with large lesions in the surgery plus radiation alone group, nor in the 16 patients with small and 8 patients with large lesions in the surgery, radiation and chemotherapy group. Minimum follow-up was one year. Other possible prognostic factors including age, tumor grade, radiation dose, and performance status were comparable for each subgroup. Lesion size in glioblastoma multiforme appears unrelated to prognosis."}
{"id": "PMID:223198", "title": "Evidence for a PGE-receptor in the rat kidney.", "content": "A membrane preparation derived from homogenates of the rat kidney has been shown to possess a high affinity for prostaglandins of the E-series. Other prostaglandins including PGI2 had characteristic but significantly weaker binding properties. A 15-hydroxyprostaglandin dehydrogenase (PGDH) was found to be associated with the membrane fraction studied. However it was possible to distinguish between this and the \"receptor\" binding by kinetic studies and by the use of a new inhibitor highly specific for PGDH.", "contents": "Evidence for a PGE-receptor in the rat kidney. A membrane preparation derived from homogenates of the rat kidney has been shown to possess a high affinity for prostaglandins of the E-series. Other prostaglandins including PGI2 had characteristic but significantly weaker binding properties. A 15-hydroxyprostaglandin dehydrogenase (PGDH) was found to be associated with the membrane fraction studied. However it was possible to distinguish between this and the \"receptor\" binding by kinetic studies and by the use of a new inhibitor highly specific for PGDH."}
{"id": "PMID:223199", "title": "Cyclic AMP formation of isolated human corpora lutea in response to HCG - interference by PGF2 alpha.", "content": "Human corpora lutea of defined ages were excised at operation, cut into pieces and incubated in the presence of HCG, PGF2 alpha and PGE2 alone or in combination. Following incubation cAMP formation in tissue and medium was determined. HCG-stimulated tissue cAMP content was most pronounced at a corpus luteum age of 7-10 days after ovulation. This stimulation was antagonized by PGF2 alpha in corpora lutea older than 6 days. PGE2 stimulated cAMP formation per se and this effect was more pronounced when HCG and PGE2 were combined. A possible role for PGF2 alpha as a luteolytic substance in the human is suggested.", "contents": "Cyclic AMP formation of isolated human corpora lutea in response to HCG - interference by PGF2 alpha. Human corpora lutea of defined ages were excised at operation, cut into pieces and incubated in the presence of HCG, PGF2 alpha and PGE2 alone or in combination. Following incubation cAMP formation in tissue and medium was determined. HCG-stimulated tissue cAMP content was most pronounced at a corpus luteum age of 7-10 days after ovulation. This stimulation was antagonized by PGF2 alpha in corpora lutea older than 6 days. PGE2 stimulated cAMP formation per se and this effect was more pronounced when HCG and PGE2 were combined. A possible role for PGF2 alpha as a luteolytic substance in the human is suggested."}
{"id": "PMID:223202", "title": "Kinetics of the D and I glycogen synthetase forms and their interconversion, in the sea scallop Pecten maximus.", "content": "In extracts from the adductor muscle of the shell-fish, Pecten maximus, glycogen synthetase (EC.2.4.1.11) was found. The enzyme occurs predominantly as D form (glucose-6-P dependent for activity). An I form (G-6-P independent) was also present. Kinetics of glycogen synthetase showed that the Ka for G-6-P in the D form was 10 fold higher than in the I form. Both forms of glycogen synthetase were interconverted through reactions catalyzed by phosphatase and kinase enzymes respectively. Glucose-6-P and Mg+2 must be present to stabilize glycogen synthetase and to activate the synthetase D phosphatase, found in the 90,000 X g protein-glycogen complex. The conversion of synthetase D to I was inhibited by F-, glycogen, ATP and UTP. When F- was present the effect of G-6-P on synthetase and phosphatase suggested that conversion involved the existence of more than a single glycogen synthetase phosphatase enzyme. ATP and Mg+2 were necessary for the conversion of synthetase I to D, and the conversion was stimulated by cAMP.", "contents": "Kinetics of the D and I glycogen synthetase forms and their interconversion, in the sea scallop Pecten maximus. In extracts from the adductor muscle of the shell-fish, Pecten maximus, glycogen synthetase (EC.2.4.1.11) was found. The enzyme occurs predominantly as D form (glucose-6-P dependent for activity). An I form (G-6-P independent) was also present. Kinetics of glycogen synthetase showed that the Ka for G-6-P in the D form was 10 fold higher than in the I form. Both forms of glycogen synthetase were interconverted through reactions catalyzed by phosphatase and kinase enzymes respectively. Glucose-6-P and Mg+2 must be present to stabilize glycogen synthetase and to activate the synthetase D phosphatase, found in the 90,000 X g protein-glycogen complex. The conversion of synthetase D to I was inhibited by F-, glycogen, ATP and UTP. When F- was present the effect of G-6-P on synthetase and phosphatase suggested that conversion involved the existence of more than a single glycogen synthetase phosphatase enzyme. ATP and Mg+2 were necessary for the conversion of synthetase I to D, and the conversion was stimulated by cAMP."}
{"id": "PMID:223203", "title": "NADH and NADPH-viologen reductases from Acinetobacter calcoaceticus.", "content": "Three pyridine nucleotide-dependent diaphorases have been isolated from Acinetobacter calcoaceticus cells and partially characterized. Two of them, with molecular weights of 165,000 and 57,000, utilize NADPH as electron donor whereas the third one (MW = 57,000) is specific for NADH. Oxidized viologen dyes, flavin nucleotides, dichlorophenol indophenol and ferricyanide can act with efficiency as acceptors in the reaction mediated by these diaphorases. The diaphorase activities have been characterized kinetically, and the effect of different inhibitors and cofactors has been also studied. The diaphorases seem to be subjected to metabolic control by oxidation and reduction.", "contents": "NADH and NADPH-viologen reductases from Acinetobacter calcoaceticus. Three pyridine nucleotide-dependent diaphorases have been isolated from Acinetobacter calcoaceticus cells and partially characterized. Two of them, with molecular weights of 165,000 and 57,000, utilize NADPH as electron donor whereas the third one (MW = 57,000) is specific for NADH. Oxidized viologen dyes, flavin nucleotides, dichlorophenol indophenol and ferricyanide can act with efficiency as acceptors in the reaction mediated by these diaphorases. The diaphorase activities have been characterized kinetically, and the effect of different inhibitors and cofactors has been also studied. The diaphorases seem to be subjected to metabolic control by oxidation and reduction."}
{"id": "PMID:223200", "title": "[Clinical comparison of the kinetics of 99mTc pyrophosphate and 99mTc methylene diphosphonate (author's transl)].", "content": "In a series of 10 patients the hematic and plasmatic clearances of 99mTc-pyrophosphate (PYP) and 99mTc-metylene-diphosphonate (MDP) have been studied. The analysis of the results shows that the elimination both hematic and plasmatic of MDP is significantly faster than that of PYP. Moreover the plasmatic elimination of PYP is faster than its hematic elimination. This fact is probably due to a partial absorption of the radionuclide on the surface of the red cells. No significant differences result in the urinary elimination of both radionuclides. As a consequence the MDP has a lower fundus activity and a lower irradiation dose to the blood and to the whole body. For those reasons this radionuclide is proposed as the preferred agent in bones scintigraphy.", "contents": "[Clinical comparison of the kinetics of 99mTc pyrophosphate and 99mTc methylene diphosphonate (author's transl)]. In a series of 10 patients the hematic and plasmatic clearances of 99mTc-pyrophosphate (PYP) and 99mTc-metylene-diphosphonate (MDP) have been studied. The analysis of the results shows that the elimination both hematic and plasmatic of MDP is significantly faster than that of PYP. Moreover the plasmatic elimination of PYP is faster than its hematic elimination. This fact is probably due to a partial absorption of the radionuclide on the surface of the red cells. No significant differences result in the urinary elimination of both radionuclides. As a consequence the MDP has a lower fundus activity and a lower irradiation dose to the blood and to the whole body. For those reasons this radionuclide is proposed as the preferred agent in bones scintigraphy."}
{"id": "PMID:223209", "title": "Studies on osteoporosis. II. Effect of estrogens and fluoride on experimental osteoporosis. A preliminary report.", "content": "Total skeletal calcium level was determined in female mice with the aid of whole body neutron activation analysis. Three months treatment with heparin produced significant osteoporosis in C3H/St(Ha) mice of 3--5 months of age. Treatment with a conjugated natural estrogen preparation (Premarin) prevented this phenomenon but high level fluoride in the drinking water failed to show preventive activity.", "contents": "Studies on osteoporosis. II. Effect of estrogens and fluoride on experimental osteoporosis. A preliminary report. Total skeletal calcium level was determined in female mice with the aid of whole body neutron activation analysis. Three months treatment with heparin produced significant osteoporosis in C3H/St(Ha) mice of 3--5 months of age. Treatment with a conjugated natural estrogen preparation (Premarin) prevented this phenomenon but high level fluoride in the drinking water failed to show preventive activity."}
{"id": "PMID:223210", "title": "Release of human chorionic somatomammotrophin from isolated perfused lobules and superfused fragments of term placenta: spontaneous liberation and the effects of cholinergic drugs, dibutyrylcyclic adenosine monophosphate and calcium.", "content": "Single isolated lobules from term placentae were bilaterally perfused with Earle's solution, and the release of human chorionic somatomammotrophin (HCS) was measured by radioimmunoassay. HCS was secreted almost exclusively to the maternal side. Concentrations released at the beginning of perfusions were quite similar to established maternal blood values (up to 10 microgram HCS/ml). Secretion then continued for at least 3 hours at a fairly linear rate. Acetylcholine, a prominent constituent of the noninnervated human placenta, and other cholinergic drugs failed to alter this pattern of hormone output in both intact lobules and dynamically superfused placental fragments. The ability of the placenta to respond to alterations in the perfusion environment was verified by stimulating the HCS secretion with 1 mM dibutyryl cyclic adenosine monophosphate and by modifying calcium concentrations. High calcium (10 mM CaCl2) led to a sustained increase of HCS release.", "contents": "Release of human chorionic somatomammotrophin from isolated perfused lobules and superfused fragments of term placenta: spontaneous liberation and the effects of cholinergic drugs, dibutyrylcyclic adenosine monophosphate and calcium. Single isolated lobules from term placentae were bilaterally perfused with Earle's solution, and the release of human chorionic somatomammotrophin (HCS) was measured by radioimmunoassay. HCS was secreted almost exclusively to the maternal side. Concentrations released at the beginning of perfusions were quite similar to established maternal blood values (up to 10 microgram HCS/ml). Secretion then continued for at least 3 hours at a fairly linear rate. Acetylcholine, a prominent constituent of the noninnervated human placenta, and other cholinergic drugs failed to alter this pattern of hormone output in both intact lobules and dynamically superfused placental fragments. The ability of the placenta to respond to alterations in the perfusion environment was verified by stimulating the HCS secretion with 1 mM dibutyryl cyclic adenosine monophosphate and by modifying calcium concentrations. High calcium (10 mM CaCl2) led to a sustained increase of HCS release."}
{"id": "PMID:223211", "title": "Influence of morphine, beta-endorphin and naloxone on the synthesis of phosphoinositides in the rat midbrain.", "content": "The effects of morphine, beta-endorphin and naloxone on the initial incorporation of 32Pi and [3H]glycerol into TPI, DPI and PI were measured in discrete subcellular fractions of the rat midbrain. Morphine and beta-endorphin significantly increased microsomal 32PI incorporation into TPI and PI but not DPI. Although neither morphine nor beta-endorphin significantly affected the levels of [3H]TPI or [3H]DPI, both agents significantly increased [3H]PI levels. All of the significant effects induced by morphine were blocked by naloxone treatment and were decreased after chronic morphine administration. However, naloxone treatment alone also mimicked all the effects of morphine except the increased incorporation of [3H]glycerol into PI. It was also found that chronic morphine treatment significantly increased the incorporation of 32Pi into synaptic TPI and DPI. This effect, however, did not show regional specificity being found in both cortical and subcortical synaptic membranes. Overall, the results suggest that the mechanisms of opioid action are closely associated with changes in the turnover of the brain phosphoinositides.", "contents": "Influence of morphine, beta-endorphin and naloxone on the synthesis of phosphoinositides in the rat midbrain. The effects of morphine, beta-endorphin and naloxone on the initial incorporation of 32Pi and [3H]glycerol into TPI, DPI and PI were measured in discrete subcellular fractions of the rat midbrain. Morphine and beta-endorphin significantly increased microsomal 32PI incorporation into TPI and PI but not DPI. Although neither morphine nor beta-endorphin significantly affected the levels of [3H]TPI or [3H]DPI, both agents significantly increased [3H]PI levels. All of the significant effects induced by morphine were blocked by naloxone treatment and were decreased after chronic morphine administration. However, naloxone treatment alone also mimicked all the effects of morphine except the increased incorporation of [3H]glycerol into PI. It was also found that chronic morphine treatment significantly increased the incorporation of 32Pi into synaptic TPI and DPI. This effect, however, did not show regional specificity being found in both cortical and subcortical synaptic membranes. Overall, the results suggest that the mechanisms of opioid action are closely associated with changes in the turnover of the brain phosphoinositides."}
{"id": "PMID:223217", "title": "[Androgenic therapy and hepatocellular carcinoma. Report of a case].", "content": "A 65 years old, female patient with acquired aplastic anemia secondary to frequent exposure to hair dye. While on treatment with anabolic steroids hormone became jaundiced and developed hepatomegaly eight months later. During laparotomy the liver was enlarged, hard, with multiple whitish nodules on its surgace but was otherwise normal. Liver biopsy showed hepatocellular carcinoma, there were not cirrhosis niether hemochromatosis. A review of the related literature was done and discussed on the experimental and clinical evidences that suggested that androgens may play same role on the etiology of liver cancer.", "contents": "[Androgenic therapy and hepatocellular carcinoma. Report of a case]. A 65 years old, female patient with acquired aplastic anemia secondary to frequent exposure to hair dye. While on treatment with anabolic steroids hormone became jaundiced and developed hepatomegaly eight months later. During laparotomy the liver was enlarged, hard, with multiple whitish nodules on its surgace but was otherwise normal. Liver biopsy showed hepatocellular carcinoma, there were not cirrhosis niether hemochromatosis. A review of the related literature was done and discussed on the experimental and clinical evidences that suggested that androgens may play same role on the etiology of liver cancer."}
{"id": "PMID:223218", "title": "[Role of parainfluenza varuses in etiology of acute respiratory infections in children (serological diagnosis)].", "content": "Serologic investigations carried out in 254 children admitted to a Clinic for Children for respiratory diseases, established a diagnosis of infection with parainfluenza virus in 19.2% of cases. The predominant age-group affected was 7--12 months and 0--6 months; the causative agent in most cases was parainfluenza type 3, followed by type 2 and then type 1. The role of parainfluenza viruses in the aetiology of laryngotracheobronchiectasis was confirmed, as well as their participation in the aetiology of pneumonia in infants. The results also showed the wide circulation of parainfluenza viruses in children and their outstanding contribution to respiratory diseases among hospitalized children within a period of four years.", "contents": "[Role of parainfluenza varuses in etiology of acute respiratory infections in children (serological diagnosis)]. Serologic investigations carried out in 254 children admitted to a Clinic for Children for respiratory diseases, established a diagnosis of infection with parainfluenza virus in 19.2% of cases. The predominant age-group affected was 7--12 months and 0--6 months; the causative agent in most cases was parainfluenza type 3, followed by type 2 and then type 1. The role of parainfluenza viruses in the aetiology of laryngotracheobronchiectasis was confirmed, as well as their participation in the aetiology of pneumonia in infants. The results also showed the wide circulation of parainfluenza viruses in children and their outstanding contribution to respiratory diseases among hospitalized children within a period of four years."}
{"id": "PMID:223220", "title": "[Disodium cromoglycate treatment of bronchial asthma and spastic bronchitis (preliminiary results)].", "content": "After a short review of the mode of action of sodium chromoglycate, the results are presented, of the treatment carried out over a three months period in a group of 31 patients of which 23 had bronchial asthma and 8 had spastic bronchitis. In 19 cases the doses of steroids that the patients were receiving were either diminished or supressed, in 14 cases the doses of broncho-dilating drugs were diminished or supressed and in 15 cases the results of the respiratory function tests were improved or much improved. A synthetic evaluation of the clinical and laboratory results showed that in 3/4 of the cases (74.2%) these were either favourable or very favourable. The treatment was well tolerated and no side-effects were noted.", "contents": "[Disodium cromoglycate treatment of bronchial asthma and spastic bronchitis (preliminiary results)]. After a short review of the mode of action of sodium chromoglycate, the results are presented, of the treatment carried out over a three months period in a group of 31 patients of which 23 had bronchial asthma and 8 had spastic bronchitis. In 19 cases the doses of steroids that the patients were receiving were either diminished or supressed, in 14 cases the doses of broncho-dilating drugs were diminished or supressed and in 15 cases the results of the respiratory function tests were improved or much improved. A synthetic evaluation of the clinical and laboratory results showed that in 3/4 of the cases (74.2%) these were either favourable or very favourable. The treatment was well tolerated and no side-effects were noted."}
{"id": "PMID:223222", "title": "[Results of intermittent biweekly treatment with rifampicin and ethambutol in silicotuberculosis].", "content": "The results were analysed, of the results obtained by the associated treatment with rifampicin and etambutol 2/7 for at least 6 months in 53 patients with silico-tuberculosis and positive bacteriologic tests. Only two of the patients in the group were in the 1-st stage of silicosis while half of the patients had cavities. Also 50% of the patients had strains showing resistance to various drugs. Only five of the patients did not receive chemotherapy before the start of the study. Immediate favourable bacteriological results were noted in 84.9% of the cases and late positive results represented 54.7%, while radiologic improvement was noted in 33.9% of the cases. The percentage of good results was higher in patients without cavities but it was not influenced by the stage of silicosis development.", "contents": "[Results of intermittent biweekly treatment with rifampicin and ethambutol in silicotuberculosis]. The results were analysed, of the results obtained by the associated treatment with rifampicin and etambutol 2/7 for at least 6 months in 53 patients with silico-tuberculosis and positive bacteriologic tests. Only two of the patients in the group were in the 1-st stage of silicosis while half of the patients had cavities. Also 50% of the patients had strains showing resistance to various drugs. Only five of the patients did not receive chemotherapy before the start of the study. Immediate favourable bacteriological results were noted in 84.9% of the cases and late positive results represented 54.7%, while radiologic improvement was noted in 33.9% of the cases. The percentage of good results was higher in patients without cavities but it was not influenced by the stage of silicosis development."}
{"id": "PMID:223221", "title": "[Indications and results of surgical treatment of the post-tuberculosis syndrome].", "content": "The post-tuberculous syndromes are more numerous and more severe following the present treatments with tuberculostatics, as compared with the past. Indications of the surgical treatment of these syndromes should be aimed at obtaining functional recovery, and they must be always adapted according to the patient's requirements. The results depend on the indications, on the technical performance, on the post-operative treatment (medical physical exercises, etc.). In the surgical treatment of the present post-tuberculous syndrome there is a supplementary risk, as compared with the surgical treatment of the evolutive tuberculosis. Prophylaxis of the post-tuberculous syndrome can be achieved by a correct medical treatment. If this is not successful the surgical treatment will be applied at the optimal time.", "contents": "[Indications and results of surgical treatment of the post-tuberculosis syndrome]. The post-tuberculous syndromes are more numerous and more severe following the present treatments with tuberculostatics, as compared with the past. Indications of the surgical treatment of these syndromes should be aimed at obtaining functional recovery, and they must be always adapted according to the patient's requirements. The results depend on the indications, on the technical performance, on the post-operative treatment (medical physical exercises, etc.). In the surgical treatment of the present post-tuberculous syndrome there is a supplementary risk, as compared with the surgical treatment of the evolutive tuberculosis. Prophylaxis of the post-tuberculous syndrome can be achieved by a correct medical treatment. If this is not successful the surgical treatment will be applied at the optimal time."}
{"id": "PMID:223231", "title": "[Nerve and artery lesions after irradiation (author's transl)].", "content": "Recent studies relating to soft tissue lesions following irradiation have been concerned with those involving nerves and arteries: Nerve root myelopathies--Brown-sequard's syndrome--spasmodic paraparesis Peripheral neuropathies--plexal disorders--peripheral lesions Carotid stenosis.", "contents": "[Nerve and artery lesions after irradiation (author's transl)]. Recent studies relating to soft tissue lesions following irradiation have been concerned with those involving nerves and arteries: Nerve root myelopathies--Brown-sequard's syndrome--spasmodic paraparesis Peripheral neuropathies--plexal disorders--peripheral lesions Carotid stenosis."}
{"id": "PMID:223225", "title": "[Importance of Australia antigen in bronchopulmonary diseases].", "content": "Australia antigen (HB Ag) was determined by electroimmunodiffusion in 327 patients with various bronchopulmonary diseases admitted to the Clinic of Pneumophthisiology. Of the total cases investigated 19 (5.8%) presented a positive HB Ag titer. It is considered that the incidence of positive HB Ag cases in the Clinic does not reflect the frequency of the disease in the general population, bearing in mind the selection of the cases in the Clinic. Determination of the HB Ag is of importance for detecting active or latent infections with hepatitis virus type B, requiring follow up and isolation of the patients as well rigurous disinfection.", "contents": "[Importance of Australia antigen in bronchopulmonary diseases]. Australia antigen (HB Ag) was determined by electroimmunodiffusion in 327 patients with various bronchopulmonary diseases admitted to the Clinic of Pneumophthisiology. Of the total cases investigated 19 (5.8%) presented a positive HB Ag titer. It is considered that the incidence of positive HB Ag cases in the Clinic does not reflect the frequency of the disease in the general population, bearing in mind the selection of the cases in the Clinic. Determination of the HB Ag is of importance for detecting active or latent infections with hepatitis virus type B, requiring follow up and isolation of the patients as well rigurous disinfection."}
{"id": "PMID:223232", "title": "A live human B-cell activator operating in isolation of other cellular influences.", "content": "Using a reversed haemolytic plaque assay, we demonstrate that live but not inactivated Epstein-Barr (EB) virus can induce human blood lymphocytes to polyclonal Ig (IgM and IgG) secretion in vitro. Unlike pokeweed mitogen this B-cell-activating effect takes place in relative absence of T cells. EB virus thus promises to be a tool for study of B cell function isolated from other cellular influences, although its mechanism of activation appears to be different from that of previously known B cell activators.", "contents": "A live human B-cell activator operating in isolation of other cellular influences. Using a reversed haemolytic plaque assay, we demonstrate that live but not inactivated Epstein-Barr (EB) virus can induce human blood lymphocytes to polyclonal Ig (IgM and IgG) secretion in vitro. Unlike pokeweed mitogen this B-cell-activating effect takes place in relative absence of T cells. EB virus thus promises to be a tool for study of B cell function isolated from other cellular influences, although its mechanism of activation appears to be different from that of previously known B cell activators."}
{"id": "PMID:223233", "title": "Etiology of sporadic aseptic meningitis in children in the Leningrad area.", "content": "The etiology of sporadic aseptic meningitis among children in the Leningrad area in 1974 was studied. 184 patients and 284 healthy children of the same age groups were studied; altogether 540 stool specimens and 99 cerebrospinal fluid specimens were collected for virus isolations and 162 pairs of sera for virus antibody assays. Mumps virus infection was the etiology of the disease only in 5% of cases. The main etiological role of enteroviruses was proved. Strains most often associated with disease were echoviruses 6 and 14, coxsackievirus A9 and nontypable strains. Additional strains isolated were echoviruses 2, 9, 11 and 20.", "contents": "Etiology of sporadic aseptic meningitis in children in the Leningrad area. The etiology of sporadic aseptic meningitis among children in the Leningrad area in 1974 was studied. 184 patients and 284 healthy children of the same age groups were studied; altogether 540 stool specimens and 99 cerebrospinal fluid specimens were collected for virus isolations and 162 pairs of sera for virus antibody assays. Mumps virus infection was the etiology of the disease only in 5% of cases. The main etiological role of enteroviruses was proved. Strains most often associated with disease were echoviruses 6 and 14, coxsackievirus A9 and nontypable strains. Additional strains isolated were echoviruses 2, 9, 11 and 20."}
{"id": "PMID:223234", "title": "A prospective study on congenital and acquired cytomegalovirus infections in infants.", "content": "A preliminary report is presented on a current prospective virological and clinical study of congenital and acquired infant cytomegalovirus (CMV) infections. During a 1-year period, 7/2200 newborn Swedish infants investigated (0.3%) had a congenital CMV infection as shown by positive virus isolation. Two of them had typical symptoms, hepatosplenomegaly and petechiae in one case and splenomegaly in the other one. All of them had a normal birth weight and normal head circumference. No sequelae have been observed during an observation period of up to 9 months. Five out of 10 control infants followed-up acquired a CMV infection within a few months. 5/7 mothers of the congenitally infected infants and 3/14 mothers of the control infants were primiparas.", "contents": "A prospective study on congenital and acquired cytomegalovirus infections in infants. A preliminary report is presented on a current prospective virological and clinical study of congenital and acquired infant cytomegalovirus (CMV) infections. During a 1-year period, 7/2200 newborn Swedish infants investigated (0.3%) had a congenital CMV infection as shown by positive virus isolation. Two of them had typical symptoms, hepatosplenomegaly and petechiae in one case and splenomegaly in the other one. All of them had a normal birth weight and normal head circumference. No sequelae have been observed during an observation period of up to 9 months. Five out of 10 control infants followed-up acquired a CMV infection within a few months. 5/7 mothers of the congenitally infected infants and 3/14 mothers of the control infants were primiparas."}
{"id": "PMID:223235", "title": "Investigation of the immune response to aerobic and anaerobic intestinal bacteria in a patient with Crohn's disease.", "content": "The immune response to aerobic and anaerobic intestinal bacteria in a patient with Crohn's disease with an intestinal fistula was investigated with various serological techniques. Two aerobic bacterial species, E. dispar and P. mirabilis, and four strict anaerobic bacterial species, B. fragilis ss. fragilis, F. varium and two different strains of C. perfringens, were isolated from fistula secretion of the patient. These strains were used as antigens for tube agglutination, passive hemagglutination, indirect immunofluorescence and immune hemolysis assays with serum specimens obtained before and after operation of the patient. Immune responses were demonstrated to the aerobic as well as to the anaerobic bacterial strains isolated from the patient's fistula. In connection with the operation an active immune response was demonstrated to the aerobic and anaerobic bacterial isolates. Antibodies belonging to IgG and IgA took part in the active immune response while IgM was very little involved. Antibodies responsible for passive hemagglutination reactions were resistant to treatment with beta-mercaptoethanol. Antibodies to aerobic and anaerobic Gram-negative rods were shown to have complement fixing activity. The importance of the demonstrated antibodies for the host's defence against normal intestinal microorganisms and the inflammatory reaction as a consequence of chronic antigenic stimulation in the diseased part of the intestine in patients with Crohn's disease is discussed.", "contents": "Investigation of the immune response to aerobic and anaerobic intestinal bacteria in a patient with Crohn's disease. The immune response to aerobic and anaerobic intestinal bacteria in a patient with Crohn's disease with an intestinal fistula was investigated with various serological techniques. Two aerobic bacterial species, E. dispar and P. mirabilis, and four strict anaerobic bacterial species, B. fragilis ss. fragilis, F. varium and two different strains of C. perfringens, were isolated from fistula secretion of the patient. These strains were used as antigens for tube agglutination, passive hemagglutination, indirect immunofluorescence and immune hemolysis assays with serum specimens obtained before and after operation of the patient. Immune responses were demonstrated to the aerobic as well as to the anaerobic bacterial strains isolated from the patient's fistula. In connection with the operation an active immune response was demonstrated to the aerobic and anaerobic bacterial isolates. Antibodies belonging to IgG and IgA took part in the active immune response while IgM was very little involved. Antibodies responsible for passive hemagglutination reactions were resistant to treatment with beta-mercaptoethanol. Antibodies to aerobic and anaerobic Gram-negative rods were shown to have complement fixing activity. The importance of the demonstrated antibodies for the host's defence against normal intestinal microorganisms and the inflammatory reaction as a consequence of chronic antigenic stimulation in the diseased part of the intestine in patients with Crohn's disease is discussed."}
{"id": "PMID:223236", "title": "[Ectopic hormone formation and tumor markers in bronchial neoplasms].", "content": "Carcinoma of the bronchus can produce several polypeptide hormones and therefore has the capacity to cause most syndromes of endocrine hyperfunction. All pituitary hormones can be synthesized ectopically; furthermore, the production of hormones from the hypothalamus (CRF), the placenta (HCG, HPL) and the C-cells of the thyroid (calcitonin), as well as parathormone and prostaglandins has been described. The paraneoplastic syndrome may often be more dangerous for the patient than the tumor growth itself, and can lead to early death. On the other hand, it may allow the early detection of an unsuspected tumor. The ectopic hormones and other nonendocrine proteins and peptides can be used as tumor markers, and can demonstrate the effect of treatment and early recurrence or metastases. An ideal tumor marker should have the following characteristics: 1. production exclusively by neoplastic tissue, 2. direct correlation with tumor size, 3. substances common to all tumor types (\"large spectrum tumor marker\") although specific tumor markers for special tumors should be available, 4. the assays must be easy and automation should be possible. At present no tumor marker satisfies all these conditions. The measurement of several tumor markers and the use of discriminant analysis may extend their diagnostic value and open the way for biochemical detection of cancer in the future.", "contents": "[Ectopic hormone formation and tumor markers in bronchial neoplasms]. Carcinoma of the bronchus can produce several polypeptide hormones and therefore has the capacity to cause most syndromes of endocrine hyperfunction. All pituitary hormones can be synthesized ectopically; furthermore, the production of hormones from the hypothalamus (CRF), the placenta (HCG, HPL) and the C-cells of the thyroid (calcitonin), as well as parathormone and prostaglandins has been described. The paraneoplastic syndrome may often be more dangerous for the patient than the tumor growth itself, and can lead to early death. On the other hand, it may allow the early detection of an unsuspected tumor. The ectopic hormones and other nonendocrine proteins and peptides can be used as tumor markers, and can demonstrate the effect of treatment and early recurrence or metastases. An ideal tumor marker should have the following characteristics: 1. production exclusively by neoplastic tissue, 2. direct correlation with tumor size, 3. substances common to all tumor types (\"large spectrum tumor marker\") although specific tumor markers for special tumors should be available, 4. the assays must be easy and automation should be possible. At present no tumor marker satisfies all these conditions. The measurement of several tumor markers and the use of discriminant analysis may extend their diagnostic value and open the way for biochemical detection of cancer in the future."}
{"id": "PMID:223237", "title": "[Preliminary results of a phase-II study with DDP (cis-diaminedichloro-platinum) in the small cell bronchogenic carcinoma].", "content": "Eleven patients with measurable, previously treated oat-cell carcinoma of the lung received DDP 80 mg/m2 once every three weeks. The drug was given as a 6-hour infusion. In 4 patients a partial remission was achieved: 2 others showed a minor tumor regression. The main toxicity was vomiting, whereas generally myelosuppression and nephrotoxicity were manageable. Based on these preliminary data, a further investigation of DDP in the treatment of oat-cell carcinoma of the lung is definitely warranted.", "contents": "[Preliminary results of a phase-II study with DDP (cis-diaminedichloro-platinum) in the small cell bronchogenic carcinoma]. Eleven patients with measurable, previously treated oat-cell carcinoma of the lung received DDP 80 mg/m2 once every three weeks. The drug was given as a 6-hour infusion. In 4 patients a partial remission was achieved: 2 others showed a minor tumor regression. The main toxicity was vomiting, whereas generally myelosuppression and nephrotoxicity were manageable. Based on these preliminary data, a further investigation of DDP in the treatment of oat-cell carcinoma of the lung is definitely warranted."}
{"id": "PMID:223238", "title": "[Fever and liver cirrhosis].", "content": "Occurrence of fever in a patient with liver cirrhosis should suggest the following: 1. Endotoxemia. Endotoxins are normally present in portal blood; in hepatic cirrhosis they are insufficiently cleared by the liver and their presence can be demonstrated in the systemic circulation by the \"limulus test\". Fever is one of the many consequences ascribed to the presence of endotoxins in the blood. 2. Infections. Cirrhosis and alcoholism (which often accompanies it) impair host defenses against bacteria and other organisms. Thus, infections are actually more frequent in hepatic cirrhosis as is shown by the example of bacterial endocarditis. Spontaneous bacterial peritonitis must be searched for carefully when ascites is present. 3. Alcoholic hepatitis. This diagnosis is established histologically. The usual symptoms, occurring with variable incidence, include anorexia, nausea and vomiting, abdominal pain, fever and jaundice in the presence of hepatomegaly, leukocytosis and an elevated SGOT. Differential diagnosis from obstructive jaundice and a severe prognosis without alcohol abstinence make early diagnosis mandatory. Its evolution in cirrhosis can be astonishingly rapid. In the absence of hepatic encephalopathy, corticosteroids do not appear to be recommended. 4. Hepatoma.", "contents": "[Fever and liver cirrhosis]. Occurrence of fever in a patient with liver cirrhosis should suggest the following: 1. Endotoxemia. Endotoxins are normally present in portal blood; in hepatic cirrhosis they are insufficiently cleared by the liver and their presence can be demonstrated in the systemic circulation by the \"limulus test\". Fever is one of the many consequences ascribed to the presence of endotoxins in the blood. 2. Infections. Cirrhosis and alcoholism (which often accompanies it) impair host defenses against bacteria and other organisms. Thus, infections are actually more frequent in hepatic cirrhosis as is shown by the example of bacterial endocarditis. Spontaneous bacterial peritonitis must be searched for carefully when ascites is present. 3. Alcoholic hepatitis. This diagnosis is established histologically. The usual symptoms, occurring with variable incidence, include anorexia, nausea and vomiting, abdominal pain, fever and jaundice in the presence of hepatomegaly, leukocytosis and an elevated SGOT. Differential diagnosis from obstructive jaundice and a severe prognosis without alcohol abstinence make early diagnosis mandatory. Its evolution in cirrhosis can be astonishingly rapid. In the absence of hepatic encephalopathy, corticosteroids do not appear to be recommended. 4. Hepatoma."}
{"id": "PMID:223239", "title": "[Icterus and cirrhosis: physiopathology].", "content": "The various factors are reviewed which may contribute to the appearance of jaundice in patients with cirrhosis. During the prehepatic phase, hemolysis, spenomegaly and a drop in coagulation factors constitute the main physiopathological mechanisms, whereas intrahepatic cholestasis, alcoholic hepatitis, hepatoma and terminal hepatic insufficiency are the principal mechanisms cited for the hepatic stage. In the posthepatic stage, attention is drawn to the increased frequency of lithiasis in cirrhotic patients and the choledochal lesions seen in chronic pancreatitis.", "contents": "[Icterus and cirrhosis: physiopathology]. The various factors are reviewed which may contribute to the appearance of jaundice in patients with cirrhosis. During the prehepatic phase, hemolysis, spenomegaly and a drop in coagulation factors constitute the main physiopathological mechanisms, whereas intrahepatic cholestasis, alcoholic hepatitis, hepatoma and terminal hepatic insufficiency are the principal mechanisms cited for the hepatic stage. In the posthepatic stage, attention is drawn to the increased frequency of lithiasis in cirrhotic patients and the choledochal lesions seen in chronic pancreatitis."}
{"id": "PMID:223242", "title": "Cycloheximide-dependent reversion of human cells transformed by MSV and chemical carcinogen.", "content": "The protein synthesis inhibitor cycloheximide, at a concentration of 0.08 microgram per milliliter, induced flat morphology within 24 to 48 hours and low saturation density in human osteosarcoma cells transformed by Kirsten murine sarcoma virus (Ki-MSV) or N-methyl-N' nitro-N-nitrosoguanidine. Removal of the protein synthesis inhibitor caused both transformed cells to revert to the transformed phenotype. The demonstration of cell-surface antigens, cross-reacted with antiserums induced by extracts of both types of transformed human cells, was dependent on the presence or absence of cycloheximide in the culture medium. The results show that protein synthesis is required to maintain the transformed state in virally or chemically transformed human cells.", "contents": "Cycloheximide-dependent reversion of human cells transformed by MSV and chemical carcinogen. The protein synthesis inhibitor cycloheximide, at a concentration of 0.08 microgram per milliliter, induced flat morphology within 24 to 48 hours and low saturation density in human osteosarcoma cells transformed by Kirsten murine sarcoma virus (Ki-MSV) or N-methyl-N' nitro-N-nitrosoguanidine. Removal of the protein synthesis inhibitor caused both transformed cells to revert to the transformed phenotype. The demonstration of cell-surface antigens, cross-reacted with antiserums induced by extracts of both types of transformed human cells, was dependent on the presence or absence of cycloheximide in the culture medium. The results show that protein synthesis is required to maintain the transformed state in virally or chemically transformed human cells."}
{"id": "PMID:223243", "title": "Cerebral cortical microfluorometry at isosbestic wavelengths for correction of vascular artifact.", "content": "Microfluorometric measurements of cerebral cortical mitochondrial respiration in vivo are obscured by hemodynamic and oximetric artifacts. Isosbestic fluorometry provides appropriate correction for these vascular phenomena and permits simultaneous evaluation of mitochondrial nicotinamide adenine dinucleotide redox state, microcirculatory volume, and hemoglobin oxygenation.", "contents": "Cerebral cortical microfluorometry at isosbestic wavelengths for correction of vascular artifact. Microfluorometric measurements of cerebral cortical mitochondrial respiration in vivo are obscured by hemodynamic and oximetric artifacts. Isosbestic fluorometry provides appropriate correction for these vascular phenomena and permits simultaneous evaluation of mitochondrial nicotinamide adenine dinucleotide redox state, microcirculatory volume, and hemoglobin oxygenation."}
{"id": "PMID:223244", "title": "Voltage-dependent calcium and potassium ion conductances: a contingency mechanism for an associative learning model.", "content": "Persistent light-induced depolarization results from Ca2+ influx across a photoreceptor membrane. The marked dependence on potential of this Ca2+ influx and a Ca+-dependent K+ efflux accounts for enhancement of the light-induced depolarization when light is paired with rotation. A positive feedback cycle between light-induced depolarization and synaptic depolarization due to stimulus pairing can explain long-lasting behavioral changes produced by associative training but not control paradigms. The sensitivity of this Ca2+ influx to intracellular levels of adenosine 3'-5'-monophosphate suggests biochemical steps for this model of associative learning.", "contents": "Voltage-dependent calcium and potassium ion conductances: a contingency mechanism for an associative learning model. Persistent light-induced depolarization results from Ca2+ influx across a photoreceptor membrane. The marked dependence on potential of this Ca2+ influx and a Ca+-dependent K+ efflux accounts for enhancement of the light-induced depolarization when light is paired with rotation. A positive feedback cycle between light-induced depolarization and synaptic depolarization due to stimulus pairing can explain long-lasting behavioral changes produced by associative training but not control paradigms. The sensitivity of this Ca2+ influx to intracellular levels of adenosine 3'-5'-monophosphate suggests biochemical steps for this model of associative learning."}
{"id": "PMID:223246", "title": "Locally aggressive fibrous histiocytoma of bone. A case report.", "content": "A fibrohistiocytic tumour involving the distal diaphysis of the left femur in a 44-year-old woman is described. The lesion had a completely benign appearance cytologically but behaved in a locally aggressive manner in that it eroded the adjacent cortical bone and even extended into the soft tissue. To the best of our knowledge, no other similar case has been documented. A lesion of the humerus has been described as an atypical fibrous histiocytoma on the basis of prominent nuclear pleomorphism; the patient involved was alive 5 years after a disarticulation. The differential diagnosis of such a locally aggressive fibrous histiocytoma of bone would include a metaphyseal fibrous defect, benign fibroxanthoma, and malignant fibrous histiocytoma. We believe that the differentiation of a locally aggressive fibrous histiocytoma from the malignant variety may be important in view of the probable differing therapeutic and prognostic implications.", "contents": "Locally aggressive fibrous histiocytoma of bone. A case report. A fibrohistiocytic tumour involving the distal diaphysis of the left femur in a 44-year-old woman is described. The lesion had a completely benign appearance cytologically but behaved in a locally aggressive manner in that it eroded the adjacent cortical bone and even extended into the soft tissue. To the best of our knowledge, no other similar case has been documented. A lesion of the humerus has been described as an atypical fibrous histiocytoma on the basis of prominent nuclear pleomorphism; the patient involved was alive 5 years after a disarticulation. The differential diagnosis of such a locally aggressive fibrous histiocytoma of bone would include a metaphyseal fibrous defect, benign fibroxanthoma, and malignant fibrous histiocytoma. We believe that the differentiation of a locally aggressive fibrous histiocytoma from the malignant variety may be important in view of the probable differing therapeutic and prognostic implications."}
{"id": "PMID:223247", "title": "Sclerosteosis in South Africa.", "content": "Sclerosteosis is a potentially lethal inherited disorder of skeletal overgrowth which has a minimum prevalence of 1 in 60,000 in the Afrikaner community of South Africa. Early presenting features are syndactyly and facial palsy, and the diagnosis should be considered in any infant of Afrikaner stock with these abnormalities. No medical treatment is available, but cosmetic surgery, cranial nerve decompression and prophylactic craniectomy be be of value.", "contents": "Sclerosteosis in South Africa. Sclerosteosis is a potentially lethal inherited disorder of skeletal overgrowth which has a minimum prevalence of 1 in 60,000 in the Afrikaner community of South Africa. Early presenting features are syndactyly and facial palsy, and the diagnosis should be considered in any infant of Afrikaner stock with these abnormalities. No medical treatment is available, but cosmetic surgery, cranial nerve decompression and prophylactic craniectomy be be of value."}
{"id": "PMID:223249", "title": "Successful islet transplantation in spontaneous diabetes.", "content": "Optimism for islet transplantation is based on reversal of diabetes artificially induced in animals by pancreatectomy or beta cell toxins. In naturally occurring diabetes, implanted islets might be destroyed by the etiologic agent of the original disease; e.g., virus infection, genetic factors, or autoimmunity. Genetically determined diabetes in obese mice, in fact, is resistant to islet transplantation. Since these mice are hyperinsulinemic and not similar to human juvenile onset diabetes (JOD), more appropriate models were sought, \"BB\" rats spontaneously develop a syndrome remarkably similar to human JOD. We have studied 279 BB rats. In 31 rats the sudden onset of severe hyperglycemia was observed. Sinc BB rats proved to be AgB2 on serological typing, WF (AgB2) donors were selected. Six hundred Wistar-Furth isolated islets were transplanted intraportally in 10 BB diabetic rats immunosuppressed with antilymphocyte serum. All 10 recipients became normoglycemic, remaining so for 1 to 6 monts. An additional animal model studied was virus-induced diabetes in mice, since viral etiology of human diabetes seems likely. DBA mice receiving encephalomyocarditis virus became severely and persistently diabetic. Eight received syngeneic fetal pancreas to the renal subcapsule and became normoglycemic. Removal of the graft 30 days later demonstrated viable islets histologically and resulted in recurrent diabetes. That virally induced murine diabetes and one spontaneous syndrome in rats which is similar to human JOD responded to beta cell implantation argues that this treatment will be effective in man.", "contents": "Successful islet transplantation in spontaneous diabetes. Optimism for islet transplantation is based on reversal of diabetes artificially induced in animals by pancreatectomy or beta cell toxins. In naturally occurring diabetes, implanted islets might be destroyed by the etiologic agent of the original disease; e.g., virus infection, genetic factors, or autoimmunity. Genetically determined diabetes in obese mice, in fact, is resistant to islet transplantation. Since these mice are hyperinsulinemic and not similar to human juvenile onset diabetes (JOD), more appropriate models were sought, \"BB\" rats spontaneously develop a syndrome remarkably similar to human JOD. We have studied 279 BB rats. In 31 rats the sudden onset of severe hyperglycemia was observed. Sinc BB rats proved to be AgB2 on serological typing, WF (AgB2) donors were selected. Six hundred Wistar-Furth isolated islets were transplanted intraportally in 10 BB diabetic rats immunosuppressed with antilymphocyte serum. All 10 recipients became normoglycemic, remaining so for 1 to 6 monts. An additional animal model studied was virus-induced diabetes in mice, since viral etiology of human diabetes seems likely. DBA mice receiving encephalomyocarditis virus became severely and persistently diabetic. Eight received syngeneic fetal pancreas to the renal subcapsule and became normoglycemic. Removal of the graft 30 days later demonstrated viable islets histologically and resulted in recurrent diabetes. That virally induced murine diabetes and one spontaneous syndrome in rats which is similar to human JOD responded to beta cell implantation argues that this treatment will be effective in man."}
{"id": "PMID:223251", "title": "Myofibroblasts in human breast tumors: an ultrastructural study.", "content": "Myofibroblasts were observed in the stroma of breast tumors in all cases examined by electron microscopy; 1 intraductal papillomatosis, 1 papillary carcinoma and 7 infiltrating duct carcinomas. The tubule- or duct-like structure in the tumor tissue were frequently surrounded by myofibroblasts which corresponded to delimiting fibroblasts in the normal breast tissue. In infiltrating duct carcinomas without tubule-like structures, myofibroblasts occurred dispersely in the stroma and they might correspond to fibroblasts in normal connective tissue. A possible role of these myofibroblasts as mesenchymal cells activated in a tumorous condition was discussed.", "contents": "Myofibroblasts in human breast tumors: an ultrastructural study. Myofibroblasts were observed in the stroma of breast tumors in all cases examined by electron microscopy; 1 intraductal papillomatosis, 1 papillary carcinoma and 7 infiltrating duct carcinomas. The tubule- or duct-like structure in the tumor tissue were frequently surrounded by myofibroblasts which corresponded to delimiting fibroblasts in the normal breast tissue. In infiltrating duct carcinomas without tubule-like structures, myofibroblasts occurred dispersely in the stroma and they might correspond to fibroblasts in normal connective tissue. A possible role of these myofibroblasts as mesenchymal cells activated in a tumorous condition was discussed."}
{"id": "PMID:223253", "title": "Direct inhibitory effects of estrogens on rat Leydig cells in vitro.", "content": "In dispersed rat interstitial cells in vitro both natural and synthetic estrogens inhibited the action of pituitary luteinizing hormone (LH), as assessed by testosterone production. The estrogens also inhibited dibutyryl cyclic AMP induced steroidogenesis, suggesting that one point of inhibition could be distal to the formation of cyclic AMP in the cells. Diethyl stilbestrol and its clinically used sodium phosphate derivative (Honvol), also affected hormone-receptor interaction when tested with rat testicular homogenates. Among estradiol, estradiol benzoate, Honvol and diethyl stilbestrol only the latter at high concentration had toxic effects on Leydig cells as noted from loss of thier viability.", "contents": "Direct inhibitory effects of estrogens on rat Leydig cells in vitro. In dispersed rat interstitial cells in vitro both natural and synthetic estrogens inhibited the action of pituitary luteinizing hormone (LH), as assessed by testosterone production. The estrogens also inhibited dibutyryl cyclic AMP induced steroidogenesis, suggesting that one point of inhibition could be distal to the formation of cyclic AMP in the cells. Diethyl stilbestrol and its clinically used sodium phosphate derivative (Honvol), also affected hormone-receptor interaction when tested with rat testicular homogenates. Among estradiol, estradiol benzoate, Honvol and diethyl stilbestrol only the latter at high concentration had toxic effects on Leydig cells as noted from loss of thier viability."}
{"id": "PMID:223248", "title": "Experimental studies on the mechanism of action of timolol.", "content": "Timolol, which binds to beta-adrenergic receptors, is a potent antagonist of the catecholamine-stimulated synthesis of cyclic AMP. However, the actual mechanism of action by which timolol reduces intraocular pressure is not readily apparent. Compared to its efficacy in human eyes, the drug is relatively ineffective in rabbit eyes. A reasonable postulate is that soon after administration, timolol blocks endogenous adrenergic stimulation contributing to the formation of aqueous humor by the ciliary processes. Nevertheless, the long-lasting reduction of intraocular pressure persists at a time when the drug is no longer bound to beta-adrenergic receptors.", "contents": "Experimental studies on the mechanism of action of timolol. Timolol, which binds to beta-adrenergic receptors, is a potent antagonist of the catecholamine-stimulated synthesis of cyclic AMP. However, the actual mechanism of action by which timolol reduces intraocular pressure is not readily apparent. Compared to its efficacy in human eyes, the drug is relatively ineffective in rabbit eyes. A reasonable postulate is that soon after administration, timolol blocks endogenous adrenergic stimulation contributing to the formation of aqueous humor by the ciliary processes. Nevertheless, the long-lasting reduction of intraocular pressure persists at a time when the drug is no longer bound to beta-adrenergic receptors."}
{"id": "PMID:223254", "title": "[Cell rounding in variant sublines of the L line caused by a moderate decrease in temperature].", "content": "Several novel variants of mouse transformed L cells are described. A distinctive trait of these variants, isolated by different methods, is a rounding of the majority of cells under the influence of the moderate cooling (at 18 degrees C for 30-60 min). In the serum-free medium, no rounding occurs. The rounding is presumably an active contraction, because it is inhibited by cytochalasin B. The comparison of the phenotype of wild-type and variant cells has shown that the exposure of cultures at 18 degrees leads to a disturbance of cell adhesion to the substratum in both the cell lines. The intensive rounding of variant cells at 18 degrees is due to some defect in their attachment to the substratum, which can be revealed not only at 18 degrees, but also at 37 degrees. By the selection procedure described in this paper, a large group of cell variants defective in adhesion to the substratum may be isolated.", "contents": "[Cell rounding in variant sublines of the L line caused by a moderate decrease in temperature]. Several novel variants of mouse transformed L cells are described. A distinctive trait of these variants, isolated by different methods, is a rounding of the majority of cells under the influence of the moderate cooling (at 18 degrees C for 30-60 min). In the serum-free medium, no rounding occurs. The rounding is presumably an active contraction, because it is inhibited by cytochalasin B. The comparison of the phenotype of wild-type and variant cells has shown that the exposure of cultures at 18 degrees leads to a disturbance of cell adhesion to the substratum in both the cell lines. The intensive rounding of variant cells at 18 degrees is due to some defect in their attachment to the substratum, which can be revealed not only at 18 degrees, but also at 37 degrees. By the selection procedure described in this paper, a large group of cell variants defective in adhesion to the substratum may be isolated."}
{"id": "PMID:223255", "title": "[Lysosomes-like thrombocyte alpha-granules: the activation and inhibition of the release of the contents in blood coagulation].", "content": "The mechanism of the release of alpha-granules constituents of thrombocytes was studied in the course of blood coagulation utilizing the fluorometric technique. The release reaction can be induced by proteolytic enzymes. The process is stimulated by the presence of extracellular Ca2+. This pattern of release reaction belongs to \"release II\" type. Aminazin can also induced release of alpha-granules constituents. Heparin inhibited release II induced by Ca2+ in citrated plasma, whereas streptase had no effect.", "contents": "[Lysosomes-like thrombocyte alpha-granules: the activation and inhibition of the release of the contents in blood coagulation]. The mechanism of the release of alpha-granules constituents of thrombocytes was studied in the course of blood coagulation utilizing the fluorometric technique. The release reaction can be induced by proteolytic enzymes. The process is stimulated by the presence of extracellular Ca2+. This pattern of release reaction belongs to \"release II\" type. Aminazin can also induced release of alpha-granules constituents. Heparin inhibited release II induced by Ca2+ in citrated plasma, whereas streptase had no effect."}
{"id": "PMID:223257", "title": "A study of lobular carcinoma of the breast based on the Third National Cancer Survey in The United States of America.", "content": "Cases in in situ and infiltrating lobular carcinoma of the breast reported in the Third National Cancer Survey were reviewed according to age, sex, race, and geographic distribution. The age-specific incidence rates indicate that there are two peak age periods of risk for invasive lobular carcinoma, the first occurring in ages 40-50 years and the second after age 65. The incidence rates for lobular carcinoma were compared to the incidence rates for intraductal and infiltrating ductal carcinoma reported from the Third National Cancer Survey and for total breast cancer from the Miyagi prefecture in Japan. These comparisons indicate that factors which influence the geographic variation in breast cancer play important roles in the etiology of infiltrating ductal carcinoma, but may have little effect upon the incidence of lobular carcinoma and intraductal carcinoma. The limitations of large histological epidemiological surveys are discussed.", "contents": "A study of lobular carcinoma of the breast based on the Third National Cancer Survey in The United States of America. Cases in in situ and infiltrating lobular carcinoma of the breast reported in the Third National Cancer Survey were reviewed according to age, sex, race, and geographic distribution. The age-specific incidence rates indicate that there are two peak age periods of risk for invasive lobular carcinoma, the first occurring in ages 40-50 years and the second after age 65. The incidence rates for lobular carcinoma were compared to the incidence rates for intraductal and infiltrating ductal carcinoma reported from the Third National Cancer Survey and for total breast cancer from the Miyagi prefecture in Japan. These comparisons indicate that factors which influence the geographic variation in breast cancer play important roles in the etiology of infiltrating ductal carcinoma, but may have little effect upon the incidence of lobular carcinoma and intraductal carcinoma. The limitations of large histological epidemiological surveys are discussed."}
{"id": "PMID:223258", "title": "[Surgical treatment of minimal breast carcinoma].", "content": "The surgical approach to minimal breast cancer is still under discussion. In fact by the term \"minimal\" three lesions are meant, namely \"lobular carcinoma in situ\", \"intraductal carcinoma\" and invasive \"microcarcinoma\". It is really difficult to indicate appropriate treatment for these tumors, also because the series reported in the literature are few and represented by a small number of cases. The present paper is a critical review of the literature on the subject. According to the most recent view lobular carcinoma in situ and intraductal carcinoma demand for radical surgery (total mastectomy) due to the high percentage of multicentricity and bilaterality of these lesions. More particularly with regard to lobular carcinoma in situ recent reports claim for a \"wait and see\" policy which is gaining favour, on the ground that the risk of developing invasive cancer in women with lobular carcinoma in situ is not so high and that the period of time between diagnosis of the lobular carcinoma and the development of the invasive cancer is usually very long. On the other side, for intraductal carcinoma, axillary dissection seems to be pleonastic due to the low percentage of secondary deposits in axillary lymph-nodes (1-3%) in women operated on for intraductal carcinoma. Invasive microcardinomas, less than 5 mm in diameter, should be considered as T1N0 tumors; actually there is no reason to treat them by a more conservative surgery than is done for T1N0 cancers, as they present the same involvement of the axillary lymph nodes. In a small series of 38 microcarcinoma observed at the Milan Cancer Institut N+ cases were 27%.", "contents": "[Surgical treatment of minimal breast carcinoma]. The surgical approach to minimal breast cancer is still under discussion. In fact by the term \"minimal\" three lesions are meant, namely \"lobular carcinoma in situ\", \"intraductal carcinoma\" and invasive \"microcarcinoma\". It is really difficult to indicate appropriate treatment for these tumors, also because the series reported in the literature are few and represented by a small number of cases. The present paper is a critical review of the literature on the subject. According to the most recent view lobular carcinoma in situ and intraductal carcinoma demand for radical surgery (total mastectomy) due to the high percentage of multicentricity and bilaterality of these lesions. More particularly with regard to lobular carcinoma in situ recent reports claim for a \"wait and see\" policy which is gaining favour, on the ground that the risk of developing invasive cancer in women with lobular carcinoma in situ is not so high and that the period of time between diagnosis of the lobular carcinoma and the development of the invasive cancer is usually very long. On the other side, for intraductal carcinoma, axillary dissection seems to be pleonastic due to the low percentage of secondary deposits in axillary lymph-nodes (1-3%) in women operated on for intraductal carcinoma. Invasive microcardinomas, less than 5 mm in diameter, should be considered as T1N0 tumors; actually there is no reason to treat them by a more conservative surgery than is done for T1N0 cancers, as they present the same involvement of the axillary lymph nodes. In a small series of 38 microcarcinoma observed at the Milan Cancer Institut N+ cases were 27%."}
{"id": "PMID:223259", "title": "Pitfalls of liver scan in Wilms' tumors.", "content": "Twenty-five patients suffering from nephroblastoma were investigated with a liver scan. The scan results were compared with surgical and pathological findings. This study suggests that different factors (i.e., primary tumor compression, local recurrence and effects of radiotherapy) may determine identical pathological patterns of the scan. Anamnestic information is very important for a correct diagnosis.", "contents": "Pitfalls of liver scan in Wilms' tumors. Twenty-five patients suffering from nephroblastoma were investigated with a liver scan. The scan results were compared with surgical and pathological findings. This study suggests that different factors (i.e., primary tumor compression, local recurrence and effects of radiotherapy) may determine identical pathological patterns of the scan. Anamnestic information is very important for a correct diagnosis."}
{"id": "PMID:223261", "title": "[Dependence of [14C] nicotinate and [35S] lipoate transport to erythrocytes on their Mg2+, Na+, K+-ATPase activity].", "content": "Nicotinic acid added to the incubation medium stimulates ATPase activity in erythrocytes and their membranes. Simultaneously the ouabain-sensitive ATPase activity is activated. The mentioned effect is not observed when lipoic acid is added to the medium. Accumulation of [14C]nicotinate and [35S]lipoate in biostructures occurs more intensely under conditions optimal for the Mg2+, Na+, K+-ATPase activity. In experiments with \"traces\" of erythrocytes it is shown that the gradient of Na+ and K+ favours to the transport of [35S] lipoate.", "contents": "[Dependence of [14C] nicotinate and [35S] lipoate transport to erythrocytes on their Mg2+, Na+, K+-ATPase activity]. Nicotinic acid added to the incubation medium stimulates ATPase activity in erythrocytes and their membranes. Simultaneously the ouabain-sensitive ATPase activity is activated. The mentioned effect is not observed when lipoic acid is added to the medium. Accumulation of [14C]nicotinate and [35S]lipoate in biostructures occurs more intensely under conditions optimal for the Mg2+, Na+, K+-ATPase activity. In experiments with \"traces\" of erythrocytes it is shown that the gradient of Na+ and K+ favours to the transport of [35S] lipoate."}
{"id": "PMID:223265", "title": "Pressure, anesthetics, and membrane structure: a spin-probe study.", "content": "Fatty acid spin-probe analyses at various depths in the membrane bilayer of intact erythrocytes indicate that compressional effects of pressure and fluidizing effects of lipid-soluble anesthetics are detectable only in hydrated regions of the membrane bilayer. Since current theories of anesthetic action cannot explain these observations, a proposal to do so is outlined.", "contents": "Pressure, anesthetics, and membrane structure: a spin-probe study. Fatty acid spin-probe analyses at various depths in the membrane bilayer of intact erythrocytes indicate that compressional effects of pressure and fluidizing effects of lipid-soluble anesthetics are detectable only in hydrated regions of the membrane bilayer. Since current theories of anesthetic action cannot explain these observations, a proposal to do so is outlined."}
{"id": "PMID:223262", "title": "[Activity of glycolysis key enzymes in subcellular structures of normal kidneys and under acute renal insufficiency].", "content": "The activity of key glycolysis enzymes (hexokinase, glucose-6-phosphatase, phosphofructokinase, fructose-diphosphatase and ketose-1-phosphate aldolase) in the kidney tissue and its subcellular structures was studied in normal rats and in rats with experimental acute renal insufficiency. It is established that considerable biochemical changes in the kidney tissues affecting all the elements of cellular structures occur under acute lesion of the kidneys. The activity of the enzymes under study under acute renal insufficiency lowers to a greater extent in those subcellular structures of the kidneys where they are mainly localized. The arising disturbances in permeability of the kidneys cellular membranes intensify the release of the mentioned enzymes to blood serum and urine, that in its turn disturbs the coordination of certain glycolysis stages.", "contents": "[Activity of glycolysis key enzymes in subcellular structures of normal kidneys and under acute renal insufficiency]. The activity of key glycolysis enzymes (hexokinase, glucose-6-phosphatase, phosphofructokinase, fructose-diphosphatase and ketose-1-phosphate aldolase) in the kidney tissue and its subcellular structures was studied in normal rats and in rats with experimental acute renal insufficiency. It is established that considerable biochemical changes in the kidney tissues affecting all the elements of cellular structures occur under acute lesion of the kidneys. The activity of the enzymes under study under acute renal insufficiency lowers to a greater extent in those subcellular structures of the kidneys where they are mainly localized. The arising disturbances in permeability of the kidneys cellular membranes intensify the release of the mentioned enzymes to blood serum and urine, that in its turn disturbs the coordination of certain glycolysis stages."}
{"id": "PMID:223266", "title": "Nerve membrane lipid fluidity: opposing effects of high pressure and ethanol.", "content": "Studies on model phospholipid membranes have shown that general anesthetics and pressure exert opposing effects--anesthetics increase and high pressure decreases membrane fluidity. The present study extends these investigations to intact nerve membranes. The fluidity of the membranes of spin-labeled crayfish claw nerves was measured with electron paramagnetic resonance spectroscopy. Nerves exposed to 5- or 10% ethanol showed a linear increase in membrane fluidity. In contrast, 100 ATA of helium pressure decreased nerve fluidity. Successive application of ethanol and pressure to the nerve produced opposing effects. The similarity of effects between model and nerve membranes supports the relevance of studies with model systems.", "contents": "Nerve membrane lipid fluidity: opposing effects of high pressure and ethanol. Studies on model phospholipid membranes have shown that general anesthetics and pressure exert opposing effects--anesthetics increase and high pressure decreases membrane fluidity. The present study extends these investigations to intact nerve membranes. The fluidity of the membranes of spin-labeled crayfish claw nerves was measured with electron paramagnetic resonance spectroscopy. Nerves exposed to 5- or 10% ethanol showed a linear increase in membrane fluidity. In contrast, 100 ATA of helium pressure decreased nerve fluidity. Successive application of ethanol and pressure to the nerve produced opposing effects. The similarity of effects between model and nerve membranes supports the relevance of studies with model systems."}
{"id": "PMID:223263", "title": "[Estimation of methods for isolation of 3':5'-AMP-dependent protein kinases from animal tissues].", "content": "Different approaches are described to isolation and purification of soluble and membrane-bound 3':5'-AMP-dependent protein kinases from different tissues and intracellular structures. Main stages of the enzyme isolation: homogenization of tissues, acidic precipitation, fractionation by ammonium sulphate, chromatography on ion-exchangers and gel filtration, are characterized.", "contents": "[Estimation of methods for isolation of 3':5'-AMP-dependent protein kinases from animal tissues]. Different approaches are described to isolation and purification of soluble and membrane-bound 3':5'-AMP-dependent protein kinases from different tissues and intracellular structures. Main stages of the enzyme isolation: homogenization of tissues, acidic precipitation, fractionation by ammonium sulphate, chromatography on ion-exchangers and gel filtration, are characterized."}
{"id": "PMID:223267", "title": "Ureterosigmoidostomy and carcinoma of the colon.", "content": "The etiology for the development of colon carcinoma associated with ureterosigmoidostomy seems to be related to the urine. The incidence of colon carcinoma associated with ureterosignoidostomy is 500 times greater than in the normal population, indicating a 5 per cent lifetime risk. The development time of these lesions varies from 6 to 50 years postoperatively but development time is significantly less in patients more than 40 years old. The possibility exists that colon carcinoma may develop in primary sigmoid urinary diversion conduits or sigmoid internal conduits to either bladder or bowel. No reported bowel carcinoma has developed in an ileal urinary diversion. Follow-up evaluation should include stools for blood every 3 months after 2 years, excretory urogram yearly after 5 years, sigmoid or colonoscopy every 5 years and barium enema every 5 years. If the patient has hematochezia or the excretory urogram demonstrates ureteral obstruction sigmoid and colonoscopy should be done.", "contents": "Ureterosigmoidostomy and carcinoma of the colon. The etiology for the development of colon carcinoma associated with ureterosigmoidostomy seems to be related to the urine. The incidence of colon carcinoma associated with ureterosignoidostomy is 500 times greater than in the normal population, indicating a 5 per cent lifetime risk. The development time of these lesions varies from 6 to 50 years postoperatively but development time is significantly less in patients more than 40 years old. The possibility exists that colon carcinoma may develop in primary sigmoid urinary diversion conduits or sigmoid internal conduits to either bladder or bowel. No reported bowel carcinoma has developed in an ileal urinary diversion. Follow-up evaluation should include stools for blood every 3 months after 2 years, excretory urogram yearly after 5 years, sigmoid or colonoscopy every 5 years and barium enema every 5 years. If the patient has hematochezia or the excretory urogram demonstrates ureteral obstruction sigmoid and colonoscopy should be done."}
{"id": "PMID:223260", "title": "[Interaction of p-nitrophenylphosphate with Na+,K+-ATPase].", "content": "The vector characteristics of the interacting Na+, K+-ATPase and ouabaine were studied in experiments on the restored ghosts of erythrocytes. It is shown that the effect of K+ on the enzyme activity is the same as in cases of using ATP and p-nitrophenylphosphate (p-NPP) as phosphorylating agents. ADP removes the p-NPP induced inhibition with ouabain. This effect is explained rather by addition of ADP to the enzyme substrate centre than by a decrease in the concentration of E1 approximately P phosphoform. Incorporation of labelled orthophosphate into p-nitrophenol (NP) in the presence of Na+, K+-ATPase preparations was not detected. It is shown that antibodies against the fraction of the brain microsomes inhibit K+-NPPases to a much less extent than Na+, K+-ATPase. The digitonin treatment does not remove (Na++ATP)-dependent increase in the K+-NPPase activity. A conclusion is drawn that the mechanisms of p-NPP hydrolysis differs from the mechanism of ATP hydrolysis.", "contents": "[Interaction of p-nitrophenylphosphate with Na+,K+-ATPase]. The vector characteristics of the interacting Na+, K+-ATPase and ouabaine were studied in experiments on the restored ghosts of erythrocytes. It is shown that the effect of K+ on the enzyme activity is the same as in cases of using ATP and p-nitrophenylphosphate (p-NPP) as phosphorylating agents. ADP removes the p-NPP induced inhibition with ouabain. This effect is explained rather by addition of ADP to the enzyme substrate centre than by a decrease in the concentration of E1 approximately P phosphoform. Incorporation of labelled orthophosphate into p-nitrophenol (NP) in the presence of Na+, K+-ATPase preparations was not detected. It is shown that antibodies against the fraction of the brain microsomes inhibit K+-NPPases to a much less extent than Na+, K+-ATPase. The digitonin treatment does not remove (Na++ATP)-dependent increase in the K+-NPPase activity. A conclusion is drawn that the mechanisms of p-NPP hydrolysis differs from the mechanism of ATP hydrolysis."}
{"id": "PMID:223270", "title": "[Immunization effectiveness of the inactivated vaccine against infectious bovine rhinotracheitis (IBR) with an oily adjuvant].", "content": "The adjuvant vaccine against infectious bovine rhinotracheitis (IBR) was tested as to its innocuousness and immunogenicity. The immunity response induced by a single or double application of different vaccine doses was evaluated according to the content of neutralization antibodies (NP) in the blood serum. A direct dependence was revealed between the size of the inoculum and NP content in the blood serum, with NP titres of 1 : 9.3; 1 : 26.6, 1 : 80 and 1 : 149 after doubled application of 1, 2, 5, and 10 ml of the vaccine. The calves inoculated at an age of one week produced antibodies in the same titres as one- to five-month-old calves. Singly inoculated animals mostly showed zero-level or low antibody titres, but revaccination induced general serum-positivity with NP titres 1 : 4 to 1 : 128. The animals which had been in contact with the IBR virus and were serologically negative during inoculation or had an NP content in the blood serum at a titre of 1 : 4 or less, gave an anamnestic response to inoculation, but revaccination did not lead to a significant rise in antibody content. Double administration of 2 ml of vaccine in four production charges induced the production of antibodies with average titres of 1 : 36, 1 : 25; 1 : 31 and 1 : 24. Inoculation of susceptible animals in non-infected herds and of clinically healthy animals in infected herds did not cause any health disorders. IBR; inactivated adjuvant vaccine; different age; different doses; immunity response; neutralization antibodies.", "contents": "[Immunization effectiveness of the inactivated vaccine against infectious bovine rhinotracheitis (IBR) with an oily adjuvant]. The adjuvant vaccine against infectious bovine rhinotracheitis (IBR) was tested as to its innocuousness and immunogenicity. The immunity response induced by a single or double application of different vaccine doses was evaluated according to the content of neutralization antibodies (NP) in the blood serum. A direct dependence was revealed between the size of the inoculum and NP content in the blood serum, with NP titres of 1 : 9.3; 1 : 26.6, 1 : 80 and 1 : 149 after doubled application of 1, 2, 5, and 10 ml of the vaccine. The calves inoculated at an age of one week produced antibodies in the same titres as one- to five-month-old calves. Singly inoculated animals mostly showed zero-level or low antibody titres, but revaccination induced general serum-positivity with NP titres 1 : 4 to 1 : 128. The animals which had been in contact with the IBR virus and were serologically negative during inoculation or had an NP content in the blood serum at a titre of 1 : 4 or less, gave an anamnestic response to inoculation, but revaccination did not lead to a significant rise in antibody content. Double administration of 2 ml of vaccine in four production charges induced the production of antibodies with average titres of 1 : 36, 1 : 25; 1 : 31 and 1 : 24. Inoculation of susceptible animals in non-infected herds and of clinically healthy animals in infected herds did not cause any health disorders. IBR; inactivated adjuvant vaccine; different age; different doses; immunity response; neutralization antibodies."}
{"id": "PMID:223271", "title": "[Effects of different growth rates in weaned piglets, starvation and hormonal action, on various metabolic parameters in the blood plasma].", "content": "Changes in concentrations of metabolites of the main nutrients in the blood plasma, caused by weaning and by different body weight gains, by starvation, exogenous adrenaline and ASTH administration were studied in 141 weaned piglets of the Large White breed at an age of 26 to 69 days. After weaning, the total protein level showed a faster decrease in the intensively growing piglets than in those with lower growth rates. This rapid decrease was induced by adrenaline. The post-weaning levels of glucose decreased irrespective of the growth rate of the piglets. Adrenaline caused hyperglycaemia and, after 48 hours of starvation, hypoglycaemia. Urea levels significantly increased after weaning. During starvation they remained unchanged, even under exposure to hormonal effects. Cholesterol concentration decreased after weaning, after ACTH and adrenaline administration also showed a decrease. The concentration of non-esterified fatty acids decreased after weaning, the decrease being more pronounced in the piglets with less intensive growth. The action of adrenaline, ACTH, together with an increased level of glucocorticoids, increased the concentration of these acids even in the state of starvation. It is assumed that early piglet weaning implies great metabolic changes which need not impair growth if their character is transient. The author evaluates the suitability of the starter used and parameters chosen for the determination of the metabolic profile of pigs.", "contents": "[Effects of different growth rates in weaned piglets, starvation and hormonal action, on various metabolic parameters in the blood plasma]. Changes in concentrations of metabolites of the main nutrients in the blood plasma, caused by weaning and by different body weight gains, by starvation, exogenous adrenaline and ASTH administration were studied in 141 weaned piglets of the Large White breed at an age of 26 to 69 days. After weaning, the total protein level showed a faster decrease in the intensively growing piglets than in those with lower growth rates. This rapid decrease was induced by adrenaline. The post-weaning levels of glucose decreased irrespective of the growth rate of the piglets. Adrenaline caused hyperglycaemia and, after 48 hours of starvation, hypoglycaemia. Urea levels significantly increased after weaning. During starvation they remained unchanged, even under exposure to hormonal effects. Cholesterol concentration decreased after weaning, after ACTH and adrenaline administration also showed a decrease. The concentration of non-esterified fatty acids decreased after weaning, the decrease being more pronounced in the piglets with less intensive growth. The action of adrenaline, ACTH, together with an increased level of glucocorticoids, increased the concentration of these acids even in the state of starvation. It is assumed that early piglet weaning implies great metabolic changes which need not impair growth if their character is transient. The author evaluates the suitability of the starter used and parameters chosen for the determination of the metabolic profile of pigs."}
{"id": "PMID:223276", "title": "[Corona- and rotavirus enteritis in newborn calves in Bulgaria].", "content": "In the course of investigations into enteritis enzootics in newly-born calves, 55 fecal samples have been studied through direct electron microscopy by the negative contrast method. Rota viruses were found in eight of them, corona viruses in 38.2 per cent of the cases, and both rota- and corona viruses in 49.1 per cent of the cases. Two types of rota-viral particles were observed: with and without supercapsids. Also two types of corona-viral particles were established. The first type was relatively monomorphic, having an average diameter of 120 nm, and length of the surface spikes of 20 nm. The second type  was pleomorphic with length of the spikes of 11 nm. Most of the fecal samples, containing corona viruses, agglutinate mice, rat and hamster erythrocytes. On studying the physical and chemical properties of the hemagglutinine, ist gradient density and antigenic patterns it was shown that it is related to the intact corona-virions. With the hemagglutination-inhibition test developed, antibodies against corona-viruses in the sera of a considerable number of the cows have been demonstrated. A precipitating antigen has been shown in a part of the fecal samples, containing rota-viruses. By studying the physical and chemical properties, its gradient density and its comparison with a refernce antigen, it has been shown that the antigen was conditioned by degraded fragments of rota-viruses. With the aid of the immunodiffusion method with a fecal antigen evolved, precipitating antibodies have been shown in 18 to 46 per cent of the cows and calves.", "contents": "[Corona- and rotavirus enteritis in newborn calves in Bulgaria]. In the course of investigations into enteritis enzootics in newly-born calves, 55 fecal samples have been studied through direct electron microscopy by the negative contrast method. Rota viruses were found in eight of them, corona viruses in 38.2 per cent of the cases, and both rota- and corona viruses in 49.1 per cent of the cases. Two types of rota-viral particles were observed: with and without supercapsids. Also two types of corona-viral particles were established. The first type was relatively monomorphic, having an average diameter of 120 nm, and length of the surface spikes of 20 nm. The second type  was pleomorphic with length of the spikes of 11 nm. Most of the fecal samples, containing corona viruses, agglutinate mice, rat and hamster erythrocytes. On studying the physical and chemical properties of the hemagglutinine, ist gradient density and antigenic patterns it was shown that it is related to the intact corona-virions. With the hemagglutination-inhibition test developed, antibodies against corona-viruses in the sera of a considerable number of the cows have been demonstrated. A precipitating antigen has been shown in a part of the fecal samples, containing rota-viruses. By studying the physical and chemical properties, its gradient density and its comparison with a refernce antigen, it has been shown that the antigen was conditioned by degraded fragments of rota-viruses. With the aid of the immunodiffusion method with a fecal antigen evolved, precipitating antibodies have been shown in 18 to 46 per cent of the cows and calves."}
{"id": "PMID:223277", "title": "[Trials to obtain a hyperimmune serum against bovine mucosal disease-virus diarrhea].", "content": "Obtained are two types of hyperimmune sera against the virus of the mucous disease--viral diarrhea (MD--VD) by means of subcutaneous and venous hyperimmunization of cattle with a live viral suspension: (a) A polyvariant hyperimmune serum, obtained by the use of four local and reference strains of the MD--VD virus with a neutralization titre against the Nadl strain of 1 : 1280. (b) Monovariant hyperimmune serum, prepared by the use of a reference strain of the MD--VD virus with a neutralization titre against the Nadl strain of 1 : 1280. On testing experimental calves and application in practice, it has not been established that the polyvariant serum possesses a marked protective effect at a dose of 1 cm3/kg.", "contents": "[Trials to obtain a hyperimmune serum against bovine mucosal disease-virus diarrhea]. Obtained are two types of hyperimmune sera against the virus of the mucous disease--viral diarrhea (MD--VD) by means of subcutaneous and venous hyperimmunization of cattle with a live viral suspension: (a) A polyvariant hyperimmune serum, obtained by the use of four local and reference strains of the MD--VD virus with a neutralization titre against the Nadl strain of 1 : 1280. (b) Monovariant hyperimmune serum, prepared by the use of a reference strain of the MD--VD virus with a neutralization titre against the Nadl strain of 1 : 1280. On testing experimental calves and application in practice, it has not been established that the polyvariant serum possesses a marked protective effect at a dose of 1 cm3/kg."}
{"id": "PMID:223278", "title": "[Concentration and purification of the infectious bovine rhinotracheitis virus (IBR)].", "content": "Various combinations of the method for the concentration and purification of the IBR virus have been tested. An easily applicable pattern is adopted with whose aid the virus is rapidly purified with a slightly reduced infectability. The pattern includes concentration of the virus through precipitation with polyethylenglycol, gel-filtration on a Sepharose 4B column and ultra-centrifugation in a linear gradient of sucrose. The virus is checked electronmicroscopically, immunoelectrophoretically and through a bioassay on a rabbit. When a rabbit is hyperimmunized with a virus thus purified, a high titre antiserum is obtained in which antibodies against bovine protein are lacking.", "contents": "[Concentration and purification of the infectious bovine rhinotracheitis virus (IBR)]. Various combinations of the method for the concentration and purification of the IBR virus have been tested. An easily applicable pattern is adopted with whose aid the virus is rapidly purified with a slightly reduced infectability. The pattern includes concentration of the virus through precipitation with polyethylenglycol, gel-filtration on a Sepharose 4B column and ultra-centrifugation in a linear gradient of sucrose. The virus is checked electronmicroscopically, immunoelectrophoretically and through a bioassay on a rabbit. When a rabbit is hyperimmunized with a virus thus purified, a high titre antiserum is obtained in which antibodies against bovine protein are lacking."}
{"id": "PMID:223279", "title": "[Isolation of adenovirus type 1 from aborted cattle fetuses].", "content": "Five adenoviral strains, typed as adenovirus type 1, were isolated from aborted cattle foetuses, taken from farms with abortions in cows. The viruses were isolated from kidneys, lungs and livers of the foetuses. They were isolated from the kidney most frequenty (three strains). Intranuclear basophilic inclusions in the alveolar epithelium of the lungs and in the tubular epithelium of the kidneys have been established in the histological investigations of the internal organs of the foetuses. The isolation of adenoviruses from foetuses has been discussed as an infectious process, emerging as a result of a transplacental infection.", "contents": "[Isolation of adenovirus type 1 from aborted cattle fetuses]. Five adenoviral strains, typed as adenovirus type 1, were isolated from aborted cattle foetuses, taken from farms with abortions in cows. The viruses were isolated from kidneys, lungs and livers of the foetuses. They were isolated from the kidney most frequenty (three strains). Intranuclear basophilic inclusions in the alveolar epithelium of the lungs and in the tubular epithelium of the kidneys have been established in the histological investigations of the internal organs of the foetuses. The isolation of adenoviruses from foetuses has been discussed as an infectious process, emerging as a result of a transplacental infection."}
{"id": "PMID:223281", "title": "Study of cell surface antigens induced by herpes simplex virus. Note I. Identification of the antigens by means of protein A-containing staphylococci.", "content": "A rapid, easy-to-perform and specific technique for the visualization of herpes simplex virus (HSV)-induced cell surface antigens is described. The technique consists in the incubation of HSV-infected cells with hyperimmune HSV antiserum and formation of rosettes with FITC-labelled Cowan strain staphylococci containing protein A. The \"nonspecific background\" of the reaction can be estimated by comparison with the rate of bacteria binding by control cells not incubated with HSV antiserum.", "contents": "Study of cell surface antigens induced by herpes simplex virus. Note I. Identification of the antigens by means of protein A-containing staphylococci. A rapid, easy-to-perform and specific technique for the visualization of herpes simplex virus (HSV)-induced cell surface antigens is described. The technique consists in the incubation of HSV-infected cells with hyperimmune HSV antiserum and formation of rosettes with FITC-labelled Cowan strain staphylococci containing protein A. The \"nonspecific background\" of the reaction can be estimated by comparison with the rate of bacteria binding by control cells not incubated with HSV antiserum."}
{"id": "PMID:223311", "title": "Identification of a sarcoma virus-coded phosphoprotein in nonproducer cells transformed by Kirsten or Harvey murine sarcoma virus.", "content": "A similar protein of 21,000 MW (p21) coded for by Harvey or Kirsten murine sarcoma virus has been identified in nonproducer cells transformed by these two viruses. Antisera prepared from rats bearing tumors induced by syngeneic transplantation of NRK cells transformed by Harvey murine sarcoma virus (Ha-MuSV) specifically precipitated the Ha-MuSV p21 from a nonproducer Balb/c mouse cell and a nonproducer dog cell transformed by Ha-MuSV. The same antisera also precipitated a similar protein, Ki-MuSV p21, from a nonproducer mink cell transformed by Kirsten murine sarcoma virus (Ki-MuSV). Both the p21 of Ha-MuSV and of Ki-MuSV are phosphoproteins. Previous studies have reported a virus-specific p21 polypeptide from translation of Ha-MuSV RNA in cell-free protein synthesis systems (W. P. Parks and E. M. Scolnick, 1977, J. Virol. 22, 711-719; T. Y. Shih, D. R. Williams, M. O. Weeks, J. M. Maryak, W. C. Vass, and E. M. Scolnick, 1978, J. Virol 27, 45-55). This p21 protein was specifically precipitated by the same anti-tumor sera. Similarly, a p21 polypeptide translated from Ki-MuSV RNA was also specifically precipitated by the antitumor sera. Therefore, it is concluded that the p21 of Ha-MuSV and Ki-MuSV are homologous proteins coded for bv homologous sequences found in the recombinant genomes of Ha-MuSV and Ki-MuSV.", "contents": "Identification of a sarcoma virus-coded phosphoprotein in nonproducer cells transformed by Kirsten or Harvey murine sarcoma virus. A similar protein of 21,000 MW (p21) coded for by Harvey or Kirsten murine sarcoma virus has been identified in nonproducer cells transformed by these two viruses. Antisera prepared from rats bearing tumors induced by syngeneic transplantation of NRK cells transformed by Harvey murine sarcoma virus (Ha-MuSV) specifically precipitated the Ha-MuSV p21 from a nonproducer Balb/c mouse cell and a nonproducer dog cell transformed by Ha-MuSV. The same antisera also precipitated a similar protein, Ki-MuSV p21, from a nonproducer mink cell transformed by Kirsten murine sarcoma virus (Ki-MuSV). Both the p21 of Ha-MuSV and of Ki-MuSV are phosphoproteins. Previous studies have reported a virus-specific p21 polypeptide from translation of Ha-MuSV RNA in cell-free protein synthesis systems (W. P. Parks and E. M. Scolnick, 1977, J. Virol. 22, 711-719; T. Y. Shih, D. R. Williams, M. O. Weeks, J. M. Maryak, W. C. Vass, and E. M. Scolnick, 1978, J. Virol 27, 45-55). This p21 protein was specifically precipitated by the same anti-tumor sera. Similarly, a p21 polypeptide translated from Ki-MuSV RNA was also specifically precipitated by the antitumor sera. Therefore, it is concluded that the p21 of Ha-MuSV and Ki-MuSV are homologous proteins coded for bv homologous sequences found in the recombinant genomes of Ha-MuSV and Ki-MuSV."}
{"id": "PMID:223322", "title": "Cell-free assembly of a polyoma-like particle from empty capsids and DNA.", "content": "A polyoma-like particle (PLP) is formed when polyoma DNA and purified empty capsids are incubated in a cell-free system. The DNA of this new particle is protected against the action of pancreatic DNase. The density of the purified PLP in CsCl is 1.32 g/cm3, which is intermediate between that of polyoma virions (1.34 g/cm3) and empty capsids (1.29 g/cm3). Purified PLP sediments at 190 S in sucrose and is stable in solutions of high ionic strength. When the DNA is extracted from PLP by the use of detergent and phenol, it is found to be doublestranded with a molecular weight of approximately 1.1 x 10(6). The particles are stable in CsCl at 4 degrees for at least 5 months. Electron micrographs indicate that highly purified PLPs stained with 2% PTA have the same appearance as polyoma capsids. Neither aggregates nor complexes bound by loose ionic bonds appear reasonable to explain these results. The evidence indicates that the DNA of this new polyoma-like particle, made under cell-free conditions, is protected by the capsid.", "contents": "Cell-free assembly of a polyoma-like particle from empty capsids and DNA. A polyoma-like particle (PLP) is formed when polyoma DNA and purified empty capsids are incubated in a cell-free system. The DNA of this new particle is protected against the action of pancreatic DNase. The density of the purified PLP in CsCl is 1.32 g/cm3, which is intermediate between that of polyoma virions (1.34 g/cm3) and empty capsids (1.29 g/cm3). Purified PLP sediments at 190 S in sucrose and is stable in solutions of high ionic strength. When the DNA is extracted from PLP by the use of detergent and phenol, it is found to be doublestranded with a molecular weight of approximately 1.1 x 10(6). The particles are stable in CsCl at 4 degrees for at least 5 months. Electron micrographs indicate that highly purified PLPs stained with 2% PTA have the same appearance as polyoma capsids. Neither aggregates nor complexes bound by loose ionic bonds appear reasonable to explain these results. The evidence indicates that the DNA of this new polyoma-like particle, made under cell-free conditions, is protected by the capsid."}
{"id": "PMID:223325", "title": "[Effect of hypophysectomy, hypophyseal explants and ACTH on the growth of human melanomas in diffusion chambers].", "content": "Under study was the hypophysis influence on the growth of human melanoma explants, cultivated in the abdominal cavity of mice and rats. The heterotransplants growth was compared in intact and hypophysectomized animals exposed to ACTH, and also the effect of the murine hypophysis explanted into the adjacent chamber compartments on the melanoma explants growth was investigated. The growth was assessed by a square area of the explants growth zones. ACTH and the hypophysis explanted were found to render a stimulating effect on the growth of tumor heterotransplants. Hypophysectomy in rats would suppress the growth of all melanoma explants under investigation. When injecting ACTH into hypophysectomized animals the growth of melanoma heterotransplants in the chambers does not differ from that in control series.", "contents": "[Effect of hypophysectomy, hypophyseal explants and ACTH on the growth of human melanomas in diffusion chambers]. Under study was the hypophysis influence on the growth of human melanoma explants, cultivated in the abdominal cavity of mice and rats. The heterotransplants growth was compared in intact and hypophysectomized animals exposed to ACTH, and also the effect of the murine hypophysis explanted into the adjacent chamber compartments on the melanoma explants growth was investigated. The growth was assessed by a square area of the explants growth zones. ACTH and the hypophysis explanted were found to render a stimulating effect on the growth of tumor heterotransplants. Hypophysectomy in rats would suppress the growth of all melanoma explants under investigation. When injecting ACTH into hypophysectomized animals the growth of melanoma heterotransplants in the chambers does not differ from that in control series."}
{"id": "PMID:223326", "title": "[Hybridization analysis of the viral sequences in the DNA of a hamster Rous sarcoma].", "content": "The nuclear genome of Syrian hamster virrion non-producer tumor contains the Rous sarcoma virus-specific nucleotide sequences. The information complexity of the proviral DNA from its tumor is similar to that for the DNA of Rous chicken sarcoma. The proviral DNA both in the hamster and chicken tumor consists of moderately reiterated and unique sequences. The avian oncornavirus-specific sequences are absent in the DNA of normal hamster tissue.", "contents": "[Hybridization analysis of the viral sequences in the DNA of a hamster Rous sarcoma]. The nuclear genome of Syrian hamster virrion non-producer tumor contains the Rous sarcoma virus-specific nucleotide sequences. The information complexity of the proviral DNA from its tumor is similar to that for the DNA of Rous chicken sarcoma. The proviral DNA both in the hamster and chicken tumor consists of moderately reiterated and unique sequences. The avian oncornavirus-specific sequences are absent in the DNA of normal hamster tissue."}
{"id": "PMID:223328", "title": "[Development of immunity to the poliomyelitis virus in infants with various methods of administering a live poliomyelitis vaccine].", "content": "The data have been obtained which indicate that the effectiveness of vaccination with live trivalent poliomyelitis vaccine may be increased and 90--100% of the vaccinated infants under 1 year of age may develop marked resistance of the alimentary tract and high antibody titers in the blood serum to the threee types of poliomyelitis virus in the course of 3 vaccinations. Some regularities of the formation of immunity to individual poliomyelitis virus types in the course of 4 vaccinations with trivalent vaccine were revealed and specified. The results indicate that the contact of vaccine virus with the oropharyngeal tissues during immunization has a favourable effect on the development of immunity. Vaccination of infants under 1 at 6-week intervals between vaccine feedings creates solid immunity in 90--100% vaccines. Administration of the next vaccine dose 6 weeks after the previous one stops multiplication of the dominating type of vaccine virus and prevents its long-term passage in the intestinal tract decreasing the probability of emergence of vaccine virus variants with increased pathogenicity.", "contents": "[Development of immunity to the poliomyelitis virus in infants with various methods of administering a live poliomyelitis vaccine]. The data have been obtained which indicate that the effectiveness of vaccination with live trivalent poliomyelitis vaccine may be increased and 90--100% of the vaccinated infants under 1 year of age may develop marked resistance of the alimentary tract and high antibody titers in the blood serum to the threee types of poliomyelitis virus in the course of 3 vaccinations. Some regularities of the formation of immunity to individual poliomyelitis virus types in the course of 4 vaccinations with trivalent vaccine were revealed and specified. The results indicate that the contact of vaccine virus with the oropharyngeal tissues during immunization has a favourable effect on the development of immunity. Vaccination of infants under 1 at 6-week intervals between vaccine feedings creates solid immunity in 90--100% vaccines. Administration of the next vaccine dose 6 weeks after the previous one stops multiplication of the dominating type of vaccine virus and prevents its long-term passage in the intestinal tract decreasing the probability of emergence of vaccine virus variants with increased pathogenicity."}
{"id": "PMID:223329", "title": "[Comparative experimental studies of the combined use of vaccines, interferon and interferon inducers in neurovirus infections].", "content": "Comparative investigations of the combined use of vaccines and interferon in tick-borne encephalitis, herpes, and acute encephalomyelitis of man showed that up to 78% of animal protection against 10--50 LD50 of intraperitoneally inoculated viruses could be achieved. Vaccination alone provided up to 56% survival of the infected mice, while administration of interferon subcutaneously or intraperitoneally in a dose of 800 units (53,300 units per 1 kilo body weight) 18--20 hours before virus gave a survival rate of 36%. The use of vaccine in combination with an interferon inducer, phage of f2 RNA, in tick-borne encephalitis gave up to 75% survival of the infected mice. Four hours after administration, interferon could be detected in mouse sera in a concentration up to 640 units/ml which in immune mice accumulated more rapidly and remained at a higher level 18 hours after inoculation of the inducer.", "contents": "[Comparative experimental studies of the combined use of vaccines, interferon and interferon inducers in neurovirus infections]. Comparative investigations of the combined use of vaccines and interferon in tick-borne encephalitis, herpes, and acute encephalomyelitis of man showed that up to 78% of animal protection against 10--50 LD50 of intraperitoneally inoculated viruses could be achieved. Vaccination alone provided up to 56% survival of the infected mice, while administration of interferon subcutaneously or intraperitoneally in a dose of 800 units (53,300 units per 1 kilo body weight) 18--20 hours before virus gave a survival rate of 36%. The use of vaccine in combination with an interferon inducer, phage of f2 RNA, in tick-borne encephalitis gave up to 75% survival of the infected mice. Four hours after administration, interferon could be detected in mouse sera in a concentration up to 640 units/ml which in immune mice accumulated more rapidly and remained at a higher level 18 hours after inoculation of the inducer."}
{"id": "PMID:223330", "title": "[Morphological data on the reproductive characteristics of the LEIV-108A and LEIV-3306 Uz strains of the Baku virus in chick fibroblast cell culture].", "content": "Electron microscopic examinations of chick fibroblast cells 24 hours after inoculation with LEIV-108A and LEIV-3306 Uz strains of Baku virus revealed the following: in the nuclei of the cells infected with the LEIV-108A strain fine granular matrices were found and virus particles were forming at the periphery of the nucleus; in the LEIV-3306Uz-infected cells virus particles were found budding from the plasma membrane of the cell.", "contents": "[Morphological data on the reproductive characteristics of the LEIV-108A and LEIV-3306 Uz strains of the Baku virus in chick fibroblast cell culture]. Electron microscopic examinations of chick fibroblast cells 24 hours after inoculation with LEIV-108A and LEIV-3306 Uz strains of Baku virus revealed the following: in the nuclei of the cells infected with the LEIV-108A strain fine granular matrices were found and virus particles were forming at the periphery of the nucleus; in the LEIV-3306Uz-infected cells virus particles were found budding from the plasma membrane of the cell."}
{"id": "PMID:223334", "title": "[Inhibition of PZ-peptidases by serum (author's transl)].", "content": "The inhibition of two PZ-peptidases by several sera was studied with the aid of methods based on the PZ-peptidase assay of W\u00fcnsch and Heidrich Clostridiopeptidase A is inhibited by all sera, whilst the PZ-peptidase from the rabbit serum is inhibited only by heterologous sera. The inhibition is weak and cannot be compared with the strong serum inhibition shown by collagenases.", "contents": "[Inhibition of PZ-peptidases by serum (author's transl)]. The inhibition of two PZ-peptidases by several sera was studied with the aid of methods based on the PZ-peptidase assay of W\u00fcnsch and Heidrich Clostridiopeptidase A is inhibited by all sera, whilst the PZ-peptidase from the rabbit serum is inhibited only by heterologous sera. The inhibition is weak and cannot be compared with the strong serum inhibition shown by collagenases."}
{"id": "PMID:223335", "title": "[Occupational metal poisoning (author's transl)].", "content": "The early diagnosis of lead poisoning -- the most common type of occupational metal poisoning -- based on the determination of the haemprecursors coproporphyrin, delta amino laevulinic acid and free erythrocyte protoporphyrin. Treatment with chelating agents increases urinary lead excretion very effectively. Clinical manifestations of mercury poisoning are different with organic and inorganic mercury compounds. Cadmium poisoning results in inhibition of non-specific enzymes. Depending on the mode of exposure, alteration of the epithelium of the renal tubules or skeletal damage is seen. The toxic effects of chromium are primarily due to direct contact and absorption. Chromium is also carcinogenic. The importance of technical prophylaxis is stressed.", "contents": "[Occupational metal poisoning (author's transl)]. The early diagnosis of lead poisoning -- the most common type of occupational metal poisoning -- based on the determination of the haemprecursors coproporphyrin, delta amino laevulinic acid and free erythrocyte protoporphyrin. Treatment with chelating agents increases urinary lead excretion very effectively. Clinical manifestations of mercury poisoning are different with organic and inorganic mercury compounds. Cadmium poisoning results in inhibition of non-specific enzymes. Depending on the mode of exposure, alteration of the epithelium of the renal tubules or skeletal damage is seen. The toxic effects of chromium are primarily due to direct contact and absorption. Chromium is also carcinogenic. The importance of technical prophylaxis is stressed."}
{"id": "PMID:223339", "title": "[Primary malignant chemodectoma of lung (author's transl)].", "content": "Intrathoracic chemodectomas are usually localized in the mediastinum. Primary solitary chemodectomas of the lung are very sparse. All cases of primary lung chemodectomas are described as non malignant tumors in literature. The morphological (light microscopy, enzyme histochemistry and enzyme cytochemistry) changes of a malignant chemodectoma of lung with metastases in regionar lymph nodes are reported in detail.", "contents": "[Primary malignant chemodectoma of lung (author's transl)]. Intrathoracic chemodectomas are usually localized in the mediastinum. Primary solitary chemodectomas of the lung are very sparse. All cases of primary lung chemodectomas are described as non malignant tumors in literature. The morphological (light microscopy, enzyme histochemistry and enzyme cytochemistry) changes of a malignant chemodectoma of lung with metastases in regionar lymph nodes are reported in detail."}
{"id": "PMID:223341", "title": "[Severe iatrogenic lesions caused by Huneke's neural therapy].", "content": "During a combined acupuncture-neural therapy-treatment on account of a gastric ulcer several lesions with vast haemorrhages in the abdominal cavity and in the retroperitoneal space on the right (lesions of the kidney) were produced. At the operation a duodenal ulcer without perforation was found. The competence of the neural therapy in its relation to the complications is discussed, the indication to the application of these forms of therapy in such cases is refused.", "contents": "[Severe iatrogenic lesions caused by Huneke's neural therapy]. During a combined acupuncture-neural therapy-treatment on account of a gastric ulcer several lesions with vast haemorrhages in the abdominal cavity and in the retroperitoneal space on the right (lesions of the kidney) were produced. At the operation a duodenal ulcer without perforation was found. The competence of the neural therapy in its relation to the complications is discussed, the indication to the application of these forms of therapy in such cases is refused."}
{"id": "PMID:223342", "title": "[Catecholamines for treatment of severe heart failure (author's transl)].", "content": "In patients with severe heart failure there is increased sympathetic-adrenergic activity functioning as a compensatory mechanism. Despite of increased plasma catecholamine levels myocardial sensivity to catecholamines administered for therapeutic reasons is not diminished. The positive inotropic effect of catecholamines is more pronounced as compared to digitalis glycosides. The therapeutic efficacy of catecholamines, particularly their capability to increase cardiac output, is strongly dependent on their action on alpha- and beta2-receptors. In order to enhance cardiac performance, catecholamines are mainly used under three clinical settings: 1. severe heart failure and cardiogenic shock secondary to acute myocardial infarction, 2. 'Low cardiac output syndrome\" following cardiac surgery, and 3. chronic congestive heart failure refractory to therapy with glycosides and diuretics. The use of catecholamines in the presence of acute myocardial infarction may be hazardous due to the accompanying increase of myocardial oxygen consumption. Among the available catecholamines, clinical interest recently focused on dopamine and dobutamine. Particularly with the primarily cardioselective beta-stimulating agent dobutamine a marked positive inotropic effect can be achieved in a range of dosage not significantly affecting heart rate and peripheral resistance. Positive inotropic agents may be even more effective when used in combination with vasodilators, which decrease impedance to left ventricular ejection.", "contents": "[Catecholamines for treatment of severe heart failure (author's transl)]. In patients with severe heart failure there is increased sympathetic-adrenergic activity functioning as a compensatory mechanism. Despite of increased plasma catecholamine levels myocardial sensivity to catecholamines administered for therapeutic reasons is not diminished. The positive inotropic effect of catecholamines is more pronounced as compared to digitalis glycosides. The therapeutic efficacy of catecholamines, particularly their capability to increase cardiac output, is strongly dependent on their action on alpha- and beta2-receptors. In order to enhance cardiac performance, catecholamines are mainly used under three clinical settings: 1. severe heart failure and cardiogenic shock secondary to acute myocardial infarction, 2. 'Low cardiac output syndrome\" following cardiac surgery, and 3. chronic congestive heart failure refractory to therapy with glycosides and diuretics. The use of catecholamines in the presence of acute myocardial infarction may be hazardous due to the accompanying increase of myocardial oxygen consumption. Among the available catecholamines, clinical interest recently focused on dopamine and dobutamine. Particularly with the primarily cardioselective beta-stimulating agent dobutamine a marked positive inotropic effect can be achieved in a range of dosage not significantly affecting heart rate and peripheral resistance. Positive inotropic agents may be even more effective when used in combination with vasodilators, which decrease impedance to left ventricular ejection."}
{"id": "PMID:223344", "title": "[Intra-articular or extra-articular substitution of cruciate ligament--a critical study (author's transl)].", "content": "Intra- and extra-articular methods of cruciate ligament substitution are available for treating old anteromedial knee-joint instability. Twelve patients with intra-articular cruciate ligament substitution (median third of the patellar ligaments as free transplant) and 24 patients with extra-articular cruicate ligament substitution (operation according to Nciholas) were examined with particular reference to improved stability as follow-up examinations, the results being subjected to comparative evaluation. Intra-artricular cruciate ligament substitution reduces or eliminates the pre-operative instability of the joint which is due to insufficiency of the cruciate liagment, whereas the extra-articular cruciate ligament substitution produces a significantly more frequent reduction of elimination of the instability of the valgus position and of the anteromedial instability. The combination of both methods to remove anteromedial instability of the knee joint may seem a very useful solution of the problem, but it should be limited to a restricted group of patients because it involves also contain disadvantages which make it unsuitable for indiscriminate application.", "contents": "[Intra-articular or extra-articular substitution of cruciate ligament--a critical study (author's transl)]. Intra- and extra-articular methods of cruciate ligament substitution are available for treating old anteromedial knee-joint instability. Twelve patients with intra-articular cruciate ligament substitution (median third of the patellar ligaments as free transplant) and 24 patients with extra-articular cruicate ligament substitution (operation according to Nciholas) were examined with particular reference to improved stability as follow-up examinations, the results being subjected to comparative evaluation. Intra-artricular cruciate ligament substitution reduces or eliminates the pre-operative instability of the joint which is due to insufficiency of the cruciate liagment, whereas the extra-articular cruciate ligament substitution produces a significantly more frequent reduction of elimination of the instability of the valgus position and of the anteromedial instability. The combination of both methods to remove anteromedial instability of the knee joint may seem a very useful solution of the problem, but it should be limited to a restricted group of patients because it involves also contain disadvantages which make it unsuitable for indiscriminate application."}
{"id": "PMID:223343", "title": "Cyanide insensitive iron superoxide dismutase in Euglena gracilis. Comparison of the reliabilities of different test systems for superoxide dismutases.", "content": "Two proteins (P1 and P2, with weights of 57,500 and 27,500 respectively) were isolated from Euglena gracilis. Both proteins show cyanide-insensitive superoxide dismutase activity in the \"classical\" superoxide dismutase assay, using xanthine-xanthine oxidase as O2.- generator. If O2.- is generated chemically (autoxidation of reduced anthraquinone), photochemically (illuminated riboflavine) or pulse radiolytically, only protein P1 but not P2 shows SOD activity. Protein P1 contains 1 g atom (determined: 0.82) iron (no Mn or Cu) per mole protein and may thus be defined as iron-superoxide dismutase. Protein P2, showing the spectral properties of a flavoprotein, exhibits the activities of ferredoxin-NADP-oxidoreductase and \"diaphorase\". The cyanide-insensitive SOD-activity of this Diaphorase\" in the xanthine oxidase-assay for superoxide dismutase makes this classical and commonly used test unreliable for assay cyanide insensitive SOD activities. The existence of the \"prokaryote-type\" of superoxide dismutase (Fe-SOD) in Euglena gracilis is exceptional for an eukaryotic, autotrophically grown organisms.", "contents": "Cyanide insensitive iron superoxide dismutase in Euglena gracilis. Comparison of the reliabilities of different test systems for superoxide dismutases. Two proteins (P1 and P2, with weights of 57,500 and 27,500 respectively) were isolated from Euglena gracilis. Both proteins show cyanide-insensitive superoxide dismutase activity in the \"classical\" superoxide dismutase assay, using xanthine-xanthine oxidase as O2.- generator. If O2.- is generated chemically (autoxidation of reduced anthraquinone), photochemically (illuminated riboflavine) or pulse radiolytically, only protein P1 but not P2 shows SOD activity. Protein P1 contains 1 g atom (determined: 0.82) iron (no Mn or Cu) per mole protein and may thus be defined as iron-superoxide dismutase. Protein P2, showing the spectral properties of a flavoprotein, exhibits the activities of ferredoxin-NADP-oxidoreductase and \"diaphorase\". The cyanide-insensitive SOD-activity of this Diaphorase\" in the xanthine oxidase-assay for superoxide dismutase makes this classical and commonly used test unreliable for assay cyanide insensitive SOD activities. The existence of the \"prokaryote-type\" of superoxide dismutase (Fe-SOD) in Euglena gracilis is exceptional for an eukaryotic, autotrophically grown organisms."}
{"id": "PMID:223347", "title": "[Nestl\u00e9 Foundation studies of nutritional problems in the 3d world].", "content": "An outline is given of the aims and activities of the Nestl\u00e9 Foundation, notably the inquiries performed at the Study center at Adiopodoum\u00e9 (Ivory Coast) about the nutrition situation, and the efforts made there to improve the protein intake by introducing new food-stuffs of high protein content.", "contents": "[Nestl\u00e9 Foundation studies of nutritional problems in the 3d world]. An outline is given of the aims and activities of the Nestl\u00e9 Foundation, notably the inquiries performed at the Study center at Adiopodoum\u00e9 (Ivory Coast) about the nutrition situation, and the efforts made there to improve the protein intake by introducing new food-stuffs of high protein content."}
{"id": "PMID:223348", "title": "[On the nature and significance of nodular renal blastoma (author's transl)].", "content": "In nephrectomy specimens from a series of 24 Wilms' tumors three different types of neoplastic lesion were found in the uninvolved kidney parenchyma: nodular renal blastema, Wilms' tumorlet and metanephric hamartomas. The histologic features of the first two abnormalities are presented. They show the following characteristics: Being found in patients of younger age they occur mostly bilateral. In older children they are associated to Wilms' tumor. They are related, as this is the case with Wilms' tumors, to certain congenital malformation syndromes. Nodular blastema has been also observed in association with Wilms' tumor in siblings. These findings suggest a genetic relationship between nodular renal blastema-nephroblastomatosis complex and Wilms' tumor. Furthermore, such lesions may represent potential progenitor stages of most nephroblastomas. The clinical implications hereof are discussed.", "contents": "[On the nature and significance of nodular renal blastoma (author's transl)]. In nephrectomy specimens from a series of 24 Wilms' tumors three different types of neoplastic lesion were found in the uninvolved kidney parenchyma: nodular renal blastema, Wilms' tumorlet and metanephric hamartomas. The histologic features of the first two abnormalities are presented. They show the following characteristics: Being found in patients of younger age they occur mostly bilateral. In older children they are associated to Wilms' tumor. They are related, as this is the case with Wilms' tumors, to certain congenital malformation syndromes. Nodular blastema has been also observed in association with Wilms' tumor in siblings. These findings suggest a genetic relationship between nodular renal blastema-nephroblastomatosis complex and Wilms' tumor. Furthermore, such lesions may represent potential progenitor stages of most nephroblastomas. The clinical implications hereof are discussed."}
{"id": "PMID:223349", "title": "[Metanephric epithelial hamartomas. A contribution to their morphology, evolution and significance (author's transl)].", "content": "In the uninvolved kidney parenchyma of three cases with Wilms' tumor neoplastic metanephric aberrations were found which represent regressive forms of the nodular renal blastema-nephroblastomatosis complex. Their histopathologic features are demonstrated. They are designated as simple or diffuse metanephric epithelial hamartomas. Small lesions show involution resulting in scars. In the central parts of larger lesions cysts and adenomas were detected. The latter were multicentric and revealed compact-epithelial, papillary-psammomatous, cystic-multilocular and tubulo-papillary forms. Their origin, possible evolution, relationship to nephroblastoma as well as their significance are discussed.", "contents": "[Metanephric epithelial hamartomas. A contribution to their morphology, evolution and significance (author's transl)]. In the uninvolved kidney parenchyma of three cases with Wilms' tumor neoplastic metanephric aberrations were found which represent regressive forms of the nodular renal blastema-nephroblastomatosis complex. Their histopathologic features are demonstrated. They are designated as simple or diffuse metanephric epithelial hamartomas. Small lesions show involution resulting in scars. In the central parts of larger lesions cysts and adenomas were detected. The latter were multicentric and revealed compact-epithelial, papillary-psammomatous, cystic-multilocular and tubulo-papillary forms. Their origin, possible evolution, relationship to nephroblastoma as well as their significance are discussed."}
{"id": "PMID:223350", "title": "[Serodiagnosis of cytomegalovirus -- (CMV) -- infections].", "content": "Specific IgM-antibodies to cytomegalovirus had been detected by both immunofluorescence and enzyme immunoassay. Using isolated nuclei instead of whole cells nonspecific reactions could be markedly reduced. -- IgM antibodies to cytomegalovirus were found in 7% of all pregnant women studied. Congenital infections could be demonstrated almost exclusively among children borne to mothers who had specific IgM antibodies during pregnancy.", "contents": "[Serodiagnosis of cytomegalovirus -- (CMV) -- infections]. Specific IgM-antibodies to cytomegalovirus had been detected by both immunofluorescence and enzyme immunoassay. Using isolated nuclei instead of whole cells nonspecific reactions could be markedly reduced. -- IgM antibodies to cytomegalovirus were found in 7% of all pregnant women studied. Congenital infections could be demonstrated almost exclusively among children borne to mothers who had specific IgM antibodies during pregnancy."}
{"id": "PMID:223351", "title": "[The importance of Walthard inclusions from the stand point of differential diagnosis of the female genital tuberculosis (author's transl)].", "content": "Walthard inclusions are described, which are frequent found like small nodules or cysts on the serosa of fallopian tubes and uterine ligaments under routine pelviscopy. The importance of Walthard inclusions is emphasized for distinguishing from the tubercles. During the three years period the incidence of Walthard inclusions from the 574 pelviscopic examinations was 19.7%.", "contents": "[The importance of Walthard inclusions from the stand point of differential diagnosis of the female genital tuberculosis (author's transl)]. Walthard inclusions are described, which are frequent found like small nodules or cysts on the serosa of fallopian tubes and uterine ligaments under routine pelviscopy. The importance of Walthard inclusions is emphasized for distinguishing from the tubercles. During the three years period the incidence of Walthard inclusions from the 574 pelviscopic examinations was 19.7%."}
{"id": "PMID:223354", "title": "Gigantism associated with a pituitary tumour secreting growth hormone and prolactin and cured by transsphenoidal hypophysectomy.", "content": "An 18-year old male is reported who presented with a history of a growtn spurt over the year preceding his admission. His height was above the 97th percentile, and he had incompletely developed secondary sexual characters. Pituitary evaluation demonstrated a moderately elevated level of growth hormone (hGH) not suppressible by a glucose load and not stimulable by TRH or by L-DOPA. Serum prolactin (PRL) concentration was also increased while gonadotrophin, thyroid and adrenal function were all subnormal. There was clear radiological evidence of a large pituitary tumour with suprasellar extension and transsphenoidal total hypophysectomy was performed. A mixed chromophobe and acidophilic adenoma was found and both growth hormone and prolactin were demonstrable in different cells of the tumour by the immunoperoxidase technique. Post-operatively the patient has hypopituitarism and levels of growth hormone and prolactin have remained low or undetectable after 6 months. Thus early diagnosis and surgical treatment of gigantism of this mixed hGH-PRL secreting pituitary tumour was associated with a cure, which contrasts with the unfavourable outcome of many of the patients previously reported.", "contents": "Gigantism associated with a pituitary tumour secreting growth hormone and prolactin and cured by transsphenoidal hypophysectomy. An 18-year old male is reported who presented with a history of a growtn spurt over the year preceding his admission. His height was above the 97th percentile, and he had incompletely developed secondary sexual characters. Pituitary evaluation demonstrated a moderately elevated level of growth hormone (hGH) not suppressible by a glucose load and not stimulable by TRH or by L-DOPA. Serum prolactin (PRL) concentration was also increased while gonadotrophin, thyroid and adrenal function were all subnormal. There was clear radiological evidence of a large pituitary tumour with suprasellar extension and transsphenoidal total hypophysectomy was performed. A mixed chromophobe and acidophilic adenoma was found and both growth hormone and prolactin were demonstrable in different cells of the tumour by the immunoperoxidase technique. Post-operatively the patient has hypopituitarism and levels of growth hormone and prolactin have remained low or undetectable after 6 months. Thus early diagnosis and surgical treatment of gigantism of this mixed hGH-PRL secreting pituitary tumour was associated with a cure, which contrasts with the unfavourable outcome of many of the patients previously reported."}
{"id": "PMID:223355", "title": "Bromocriptine-induced modulation of plasma aldosterone response to acute stimulations.", "content": "The influence of the dopaminergic agent 2-bromoergocryptine on plasma aldosterone response to acute stimulations was assessed in 14 normal male volunteers. Without modifying basal plasma aldosterone levels or urinary aldosterone excretion, bromocriptine retarded and diminished significantly the plasma aldosterone response to angiotensin II or ACTH, but did not alter the response to upright posture. These results point to a bromocriptine-induced modulation of the plasma aldosterone response to direct stimulations at the adrenal level. The present work brings further evidence for an effect of the dopaminergic system on the physiological control of aldosterone.", "contents": "Bromocriptine-induced modulation of plasma aldosterone response to acute stimulations. The influence of the dopaminergic agent 2-bromoergocryptine on plasma aldosterone response to acute stimulations was assessed in 14 normal male volunteers. Without modifying basal plasma aldosterone levels or urinary aldosterone excretion, bromocriptine retarded and diminished significantly the plasma aldosterone response to angiotensin II or ACTH, but did not alter the response to upright posture. These results point to a bromocriptine-induced modulation of the plasma aldosterone response to direct stimulations at the adrenal level. The present work brings further evidence for an effect of the dopaminergic system on the physiological control of aldosterone."}
{"id": "PMID:223353", "title": "[Cyclic nucleotide metabolic disorder in brain tumors].", "content": "The content of cAMP and cGMP as well as their ratio in the tissues of different cerebral tumors in humans were studied. The concentration of both cyclic nucleotides in tumors of the brain was found to vary widely. The richest information on disorders of metabolism of these substances may be gained from the ratio of cAMP and cGMP concentrations, which statistically is significantly reduced in the neoplasm as compared to the ratio in the cerebral tissue. Bearing in mind the principal possibility of correcting this ratio, further study of the metabolism of cyclic nucleotides in cerebral tumors holds promise for their treatment.", "contents": "[Cyclic nucleotide metabolic disorder in brain tumors]. The content of cAMP and cGMP as well as their ratio in the tissues of different cerebral tumors in humans were studied. The concentration of both cyclic nucleotides in tumors of the brain was found to vary widely. The richest information on disorders of metabolism of these substances may be gained from the ratio of cAMP and cGMP concentrations, which statistically is significantly reduced in the neoplasm as compared to the ratio in the cerebral tissue. Bearing in mind the principal possibility of correcting this ratio, further study of the metabolism of cyclic nucleotides in cerebral tumors holds promise for their treatment."}
{"id": "PMID:223352", "title": "[State of the blood coagulation in glial tumors of the brain].", "content": "The data presented may be of definite value in the prevention of hemorrhage and thrombosis in patients with malignant glial tumors. A malignant glioma may lead to increased activity of the blood coagulation system (BCS). Preoperative staining of the tumor was not attended by marked changes in the BCS and blood viscocity, though a tendency towards an increase in BCS activity according to some of the indices may sometimes be noted. Chemotherapy with nitrosourea and methotrexate was attended by thrombocytopenia but there was practically no changes in the other BCS indices. The postoperative period is usually marked by increased BCS activity according to most of the indices. Increased blood viscocity is often encountered in patients with glial cerebral tumors in the preoperative and postoperative periods, which is evidently due to the intensive dehydration therapy to which they are subjected in marked increase of intracranial pressure.", "contents": "[State of the blood coagulation in glial tumors of the brain]. The data presented may be of definite value in the prevention of hemorrhage and thrombosis in patients with malignant glial tumors. A malignant glioma may lead to increased activity of the blood coagulation system (BCS). Preoperative staining of the tumor was not attended by marked changes in the BCS and blood viscocity, though a tendency towards an increase in BCS activity according to some of the indices may sometimes be noted. Chemotherapy with nitrosourea and methotrexate was attended by thrombocytopenia but there was practically no changes in the other BCS indices. The postoperative period is usually marked by increased BCS activity according to most of the indices. Increased blood viscocity is often encountered in patients with glial cerebral tumors in the preoperative and postoperative periods, which is evidently due to the intensive dehydration therapy to which they are subjected in marked increase of intracranial pressure."}
{"id": "PMID:223356", "title": "Cushing's syndrome due to adrenocortical carcinoma - a comphrensive clinical and biochemical study of patients treated by surgery and chemotherapy.", "content": "Four post-menopausal women had Cushing's syndrome due to adrenal cortical carcinomas. Comprehensive analyses of blood and urinary steroids showed that although the steroid profiles differed between patients, the pattern in each patient remained almost constant as the disease progressed, or remitted due to therapy. Elevations of serum testosterone and oestradiol were commensurate with the extent of virilisation, and the urinary output of aldosterone was associated with the severity of hypertension. A new finding was that all had substantially increased urinary free deoxycorticosterone. Complete surgical removal of the primary tumours was impossible but when most of the tumour tissue was removed, full clinical and biochemical remissions were obtained for a short time in 2 patients. One patient obtained a clinical and biochemical remission from op'DDD. In another patient the drug caused reduction both in blood pressure and in urinary aldosterone excretion, but there were unpleasant side effects. A third patient could not tolerate op'DDD. Metyrapone therapy produced neither clinical nor biochemical improvement in 3 patients. The mean duration of survival was 17 months after the first symptoms and 10 months from the date of operation. Despite advances in drug therapy, adrenal cortical carcinoma remains a lethal disease. Biochemical screening of multiple steroids offers a means of early diagnosis and disease monitoring. Extensive surgical removal of the tumour offers the best chance of a clinical and biochemical remission.", "contents": "Cushing's syndrome due to adrenocortical carcinoma - a comphrensive clinical and biochemical study of patients treated by surgery and chemotherapy. Four post-menopausal women had Cushing's syndrome due to adrenal cortical carcinomas. Comprehensive analyses of blood and urinary steroids showed that although the steroid profiles differed between patients, the pattern in each patient remained almost constant as the disease progressed, or remitted due to therapy. Elevations of serum testosterone and oestradiol were commensurate with the extent of virilisation, and the urinary output of aldosterone was associated with the severity of hypertension. A new finding was that all had substantially increased urinary free deoxycorticosterone. Complete surgical removal of the primary tumours was impossible but when most of the tumour tissue was removed, full clinical and biochemical remissions were obtained for a short time in 2 patients. One patient obtained a clinical and biochemical remission from op'DDD. In another patient the drug caused reduction both in blood pressure and in urinary aldosterone excretion, but there were unpleasant side effects. A third patient could not tolerate op'DDD. Metyrapone therapy produced neither clinical nor biochemical improvement in 3 patients. The mean duration of survival was 17 months after the first symptoms and 10 months from the date of operation. Despite advances in drug therapy, adrenal cortical carcinoma remains a lethal disease. Biochemical screening of multiple steroids offers a means of early diagnosis and disease monitoring. Extensive surgical removal of the tumour offers the best chance of a clinical and biochemical remission."}
{"id": "PMID:223357", "title": "Plasma cortisol profiles in Cushing's syndrome.", "content": "Plasma cortisol profiles were studied by the frequent sampling method in 5 patients with Cushing's disease (CD), 7 patients with Cushing's syndrome due to adrenocortical adenoma (AA), and one patient with bronchogenic carcinoma. Plasma ACTH was measured by radioimmunoassay at 10 min intervals in 2 of the subjects. In CD, there was distinct episodic secretion of cortisol and ACTH; the coefficients of variation about the mean plasma cortisol concentration ranged from 24 to 27%; plasma ACTH ranged from zero to 455 pg/ml with a mean of 94 pg/ml. In AA, the tumour secreted cortisol at a constant rate with little fluctuation; the coefficients of variation of plasma cortisol concentration ranged from 8 to 14%; plasma concentrations of ACTH were always near zero. In the patient with bronchogenic carcinoma, the coefficient of variation of cortisol was 14%. These results were apparent even in profiles of plasma cortisol concentrations measured over only a 6 h period. It is concluded that characteristics of plasma cortisol and ACTH secretory patterns are helpful in differentiating Cushing's syndrome of differing aetiology.", "contents": "Plasma cortisol profiles in Cushing's syndrome. Plasma cortisol profiles were studied by the frequent sampling method in 5 patients with Cushing's disease (CD), 7 patients with Cushing's syndrome due to adrenocortical adenoma (AA), and one patient with bronchogenic carcinoma. Plasma ACTH was measured by radioimmunoassay at 10 min intervals in 2 of the subjects. In CD, there was distinct episodic secretion of cortisol and ACTH; the coefficients of variation about the mean plasma cortisol concentration ranged from 24 to 27%; plasma ACTH ranged from zero to 455 pg/ml with a mean of 94 pg/ml. In AA, the tumour secreted cortisol at a constant rate with little fluctuation; the coefficients of variation of plasma cortisol concentration ranged from 8 to 14%; plasma concentrations of ACTH were always near zero. In the patient with bronchogenic carcinoma, the coefficient of variation of cortisol was 14%. These results were apparent even in profiles of plasma cortisol concentrations measured over only a 6 h period. It is concluded that characteristics of plasma cortisol and ACTH secretory patterns are helpful in differentiating Cushing's syndrome of differing aetiology."}
{"id": "PMID:223358", "title": "Different biological action of corticosteroids, corticosterone and cortisol, as a base of zonal function of adrenal cortex.", "content": "The effects of corticosterone and cortisol in concentrations attainable in the adrenal gland were studied on ACTH-induced steroidogenesis in cultured cortical cells of foetal human and rat adrenals. Corticosterone at a concentration of 5.8 x 10(-5) mol/l clearly inhibited cortisol production (65.5%; P less than 0.005) and simultaneously increased androgen production in tissue culture of foetal human adrenals. Cortisol at a concentration of 2.8 x 10(-4) mol/l clearly inhibited 18-OH-DOC (74.0%, P less than 0.001) and aldosterone (83.7% P less than 0.005) production in tissue culture of foetal rat adrenals. In primary culture of foetal human adrenals cortisol did not decrease aldosterone production absolutely, but it significantly decreased the relative amount of aldosterone with respect to corticosterone. Cortisol did not inhibit corticosterone production in either culture. The results demonstrate that cortisol and corticosterone have qualitatively different effects on adrenal steroidogenesis and that these steroids may play a basic role in the functional zonation of the adrenal gland.", "contents": "Different biological action of corticosteroids, corticosterone and cortisol, as a base of zonal function of adrenal cortex. The effects of corticosterone and cortisol in concentrations attainable in the adrenal gland were studied on ACTH-induced steroidogenesis in cultured cortical cells of foetal human and rat adrenals. Corticosterone at a concentration of 5.8 x 10(-5) mol/l clearly inhibited cortisol production (65.5%; P less than 0.005) and simultaneously increased androgen production in tissue culture of foetal human adrenals. Cortisol at a concentration of 2.8 x 10(-4) mol/l clearly inhibited 18-OH-DOC (74.0%, P less than 0.001) and aldosterone (83.7% P less than 0.005) production in tissue culture of foetal rat adrenals. In primary culture of foetal human adrenals cortisol did not decrease aldosterone production absolutely, but it significantly decreased the relative amount of aldosterone with respect to corticosterone. Cortisol did not inhibit corticosterone production in either culture. The results demonstrate that cortisol and corticosterone have qualitatively different effects on adrenal steroidogenesis and that these steroids may play a basic role in the functional zonation of the adrenal gland."}
{"id": "PMID:223359", "title": "Early increase of cyclic adenosine monophosphate level induced by erythropoietin on rabbit bone marrow cell suspensions.", "content": "The effects of an erythropoietin (Ep)-rich plasma fraction and of a commercial preparation of purified Ep (Step I) on the cyclic adenosine monophosphate (cAMP) levels of suspended rabbit bone marrow cells at different incubation times (up to 10 min) were investigated. Both Ep preparations caused an early increase in cAMP concentration: using the plasma fraction a significant increase was found at the 6th, 7th, 9th and 10th min of incubation, whereas the purified Ep produces a significant increase at all incubation times, starting from 1 min. No effect was observed following incubation with fluorescein isothiocyanate (FITC)-inactivated Ep. These findings are discussed and possible role of cAMP as the intracellular messenger for Ep action is suggested.", "contents": "Early increase of cyclic adenosine monophosphate level induced by erythropoietin on rabbit bone marrow cell suspensions. The effects of an erythropoietin (Ep)-rich plasma fraction and of a commercial preparation of purified Ep (Step I) on the cyclic adenosine monophosphate (cAMP) levels of suspended rabbit bone marrow cells at different incubation times (up to 10 min) were investigated. Both Ep preparations caused an early increase in cAMP concentration: using the plasma fraction a significant increase was found at the 6th, 7th, 9th and 10th min of incubation, whereas the purified Ep produces a significant increase at all incubation times, starting from 1 min. No effect was observed following incubation with fluorescein isothiocyanate (FITC)-inactivated Ep. These findings are discussed and possible role of cAMP as the intracellular messenger for Ep action is suggested."}
{"id": "PMID:223360", "title": "Pseudo-Chediak-Higashi anomaly in acute myeloid leukaemia. An electron microscopical study.", "content": "2 cases of acute myeloid leukaemia with inclusion bodies are presented. The inclusions were found mainly in the blast cells but could also be encountered in lymphocytes and plasma cells. Cytochemical and ultrastructural studies showed a great resemblance of these inclusions to the ones found in Chediak-Higashi anomaly, i.e., high acid phosphatase activity, varying in size of inclusions from clusters of small granules to hugh inclusion, sometimes found in vacuoles, featuring fusion of lysosomes.", "contents": "Pseudo-Chediak-Higashi anomaly in acute myeloid leukaemia. An electron microscopical study. 2 cases of acute myeloid leukaemia with inclusion bodies are presented. The inclusions were found mainly in the blast cells but could also be encountered in lymphocytes and plasma cells. Cytochemical and ultrastructural studies showed a great resemblance of these inclusions to the ones found in Chediak-Higashi anomaly, i.e., high acid phosphatase activity, varying in size of inclusions from clusters of small granules to hugh inclusion, sometimes found in vacuoles, featuring fusion of lysosomes."}
{"id": "PMID:223361", "title": "The central nervous system in canine giant axonal neuropathy.", "content": "The pathology of the central nervous system (CNS) in a dog with giant axonal neuropathy (GAN) is presented. Swollen axons containing excessive and disorganised neurofilaments were present in the spinal cord, mainly at the distal portions of long tracts. The fasiculus gracilis and dorsal spinocerebellar tracts were affected only in the rostral cervical cord while the lateral cortico spinal tract was principally involved in the lower thoracic and lumbar cord. Occasional swellings were also found in the central dorsal columns of the rostral lumbar segments and in the dorsal and intermediate grey matter. The nuclei gracilis and cuneatus, restiform body and ventral spinocerebellar tracts were all involved in the brain stem. Spheroids were seen in the white matter of the rostral cerebellar vermis and in the granule cell layer. The brachium of the superior colliculus contained swollen axons and the cortex was diffusely involved with spheroids. The distribution was of a distal axonopathy and the cortical changes provided an explanation for the abnormal EEG and mental retardation found in some human patients.", "contents": "The central nervous system in canine giant axonal neuropathy. The pathology of the central nervous system (CNS) in a dog with giant axonal neuropathy (GAN) is presented. Swollen axons containing excessive and disorganised neurofilaments were present in the spinal cord, mainly at the distal portions of long tracts. The fasiculus gracilis and dorsal spinocerebellar tracts were affected only in the rostral cervical cord while the lateral cortico spinal tract was principally involved in the lower thoracic and lumbar cord. Occasional swellings were also found in the central dorsal columns of the rostral lumbar segments and in the dorsal and intermediate grey matter. The nuclei gracilis and cuneatus, restiform body and ventral spinocerebellar tracts were all involved in the brain stem. Spheroids were seen in the white matter of the rostral cerebellar vermis and in the granule cell layer. The brachium of the superior colliculus contained swollen axons and the cortex was diffusely involved with spheroids. The distribution was of a distal axonopathy and the cortical changes provided an explanation for the abnormal EEG and mental retardation found in some human patients."}
{"id": "PMID:223362", "title": "On the pathogenesis of mitochondrial myopathies. An experimental study.", "content": "The intra-arterial injection of 2-4 dinitrophenol, an uncoupler of oxidative phosphorylation, resulted in the production of ragged red fibers. The ultrastructure of these fibers showed intramitochondrial paracrystalline inclusions, laminar and fingerprint bodies. Antimycin A and oligomycin injection (which inhibit mitochondrial respiration) only caused swelling and disruption of the mitochondria. An increase in muscle lactic acid, decrease in ATP, glycogen and phosphocreatine was observed after the injection of all these agents. This indicates that lactic acidosis has no significant role in the pathogenesis of mitochondrial pathology. It is concluded that mitochondrial changes are a morphological expression of uncoupled but intact mitochondrial respiration.", "contents": "On the pathogenesis of mitochondrial myopathies. An experimental study. The intra-arterial injection of 2-4 dinitrophenol, an uncoupler of oxidative phosphorylation, resulted in the production of ragged red fibers. The ultrastructure of these fibers showed intramitochondrial paracrystalline inclusions, laminar and fingerprint bodies. Antimycin A and oligomycin injection (which inhibit mitochondrial respiration) only caused swelling and disruption of the mitochondria. An increase in muscle lactic acid, decrease in ATP, glycogen and phosphocreatine was observed after the injection of all these agents. This indicates that lactic acidosis has no significant role in the pathogenesis of mitochondrial pathology. It is concluded that mitochondrial changes are a morphological expression of uncoupled but intact mitochondrial respiration."}
{"id": "PMID:223363", "title": "Two cases of mucopolysaccharidosis type III (Sanfilippo). An anatomopathological study.", "content": "Anatomopathological studies of one case of Sanfilippo disease types A and C, respectively, are presented. The storage phenomenon is very severe in the central as well as in the peripheral nervous system of both patients. Light microscopy does not show significant differences between the two cases. Electron microscopy of the nervous system reveals in both cases the presence of variable amounts of zebra bodies and of membrano-granulo-vacuolar inclusions. The presence of larger amounts of zebra bodies in the type A case and of larger quantities of membrano-granulo-vacuolar inclusions in the type C case constitute probably a nondistinctive feature between the two types. Light and electron microscopic studies of visceral organs do not disclose significant differences either. It is concluded that no major morphological differences between Sanfilippo disease types A and C can be observed.", "contents": "Two cases of mucopolysaccharidosis type III (Sanfilippo). An anatomopathological study. Anatomopathological studies of one case of Sanfilippo disease types A and C, respectively, are presented. The storage phenomenon is very severe in the central as well as in the peripheral nervous system of both patients. Light microscopy does not show significant differences between the two cases. Electron microscopy of the nervous system reveals in both cases the presence of variable amounts of zebra bodies and of membrano-granulo-vacuolar inclusions. The presence of larger amounts of zebra bodies in the type A case and of larger quantities of membrano-granulo-vacuolar inclusions in the type C case constitute probably a nondistinctive feature between the two types. Light and electron microscopic studies of visceral organs do not disclose significant differences either. It is concluded that no major morphological differences between Sanfilippo disease types A and C can be observed."}
{"id": "PMID:223364", "title": "Differential effects of chloroquine and of several other amphiphilic cationic drugs upon rat choroid plexus.", "content": "Several cationic amphiphilic drugs, each of which is known to induce generalized lipidosis in rats, were compared with respect to their cytological effects on rat choroid plexus epithelium. Chloroquine induced large cytoplasmic vacuoles, whereas the other drugs (quinacrine, 4,4'-diethylaminoethoxyhexestrol, chlorphentermine, iprindole, 1-chloro-amitriptyline, clomipramine) caused formation of lamellated or crystalloid inclusions as usually seen in drug-induced lipidosis. The ultrastructure of the chloroquine-induced vacuoles suggested storage of water-soluble materials (polar lipids and/or non-lipid materials) in addition to non-water-soluble polar lipids.", "contents": "Differential effects of chloroquine and of several other amphiphilic cationic drugs upon rat choroid plexus. Several cationic amphiphilic drugs, each of which is known to induce generalized lipidosis in rats, were compared with respect to their cytological effects on rat choroid plexus epithelium. Chloroquine induced large cytoplasmic vacuoles, whereas the other drugs (quinacrine, 4,4'-diethylaminoethoxyhexestrol, chlorphentermine, iprindole, 1-chloro-amitriptyline, clomipramine) caused formation of lamellated or crystalloid inclusions as usually seen in drug-induced lipidosis. The ultrastructure of the chloroquine-induced vacuoles suggested storage of water-soluble materials (polar lipids and/or non-lipid materials) in addition to non-water-soluble polar lipids."}
{"id": "PMID:223365", "title": "Subperineurial space of the sural nerve in various peripheral nerve diseases.", "content": "The size of the subperineurial space of the sural nerve has been evaluated quantitatively in 69 cases of various peripheral nerve diseases and in controls. A significant increase was found in beriberi neuropathy (6 cases) and idiopathic polyradiculoneuropathy (9 cases) as compared with the control (8 cases). On electron microscopy a few macrophages, fibroblast processes, collagen fibrils with a diameter of 50 nm, microfibrils with a diameter of 8 nm, and amorphous material were observed in both the enlarged subperineural space and the endoneurial intercellular space. They were less frequently observed in controls. No significant correlation was found between the size of subperineurial space and the density of myelinated fibers.", "contents": "Subperineurial space of the sural nerve in various peripheral nerve diseases. The size of the subperineurial space of the sural nerve has been evaluated quantitatively in 69 cases of various peripheral nerve diseases and in controls. A significant increase was found in beriberi neuropathy (6 cases) and idiopathic polyradiculoneuropathy (9 cases) as compared with the control (8 cases). On electron microscopy a few macrophages, fibroblast processes, collagen fibrils with a diameter of 50 nm, microfibrils with a diameter of 8 nm, and amorphous material were observed in both the enlarged subperineural space and the endoneurial intercellular space. They were less frequently observed in controls. No significant correlation was found between the size of subperineurial space and the density of myelinated fibers."}
{"id": "PMID:223366", "title": "Growth hormone-producing pituitary adenoma with giant secretory granules.", "content": "Unusually large, oval and pleomorphic secretory granules were noted by electron microscopy in an acidophilic adenoma of the pituitary. The tumor, which was removed by surgery from a 42-year-old woman with elevated blood growth hormone levels and the clinical features of acromegaly, was found to contain growth hormone by the immunoperoxidase technique. This ultrastructural abnormality of secretory granules was not reported so far and was not seen among the 58 cases of growth hormone-producing adenomas investigated in our laboratory. The present case clearly shows that the cytogenesis and cellular composition of pituitary adenomas cannot be determined by solely examining the size and shape of secretory granules.", "contents": "Growth hormone-producing pituitary adenoma with giant secretory granules. Unusually large, oval and pleomorphic secretory granules were noted by electron microscopy in an acidophilic adenoma of the pituitary. The tumor, which was removed by surgery from a 42-year-old woman with elevated blood growth hormone levels and the clinical features of acromegaly, was found to contain growth hormone by the immunoperoxidase technique. This ultrastructural abnormality of secretory granules was not reported so far and was not seen among the 58 cases of growth hormone-producing adenomas investigated in our laboratory. The present case clearly shows that the cytogenesis and cellular composition of pituitary adenomas cannot be determined by solely examining the size and shape of secretory granules."}
{"id": "PMID:223367", "title": "Growth of the WW strain of Theiler virus in mouse central nervous system organotypic culture.", "content": "Myelinated organotypic cultures of mouse central nervous system (CNS) provide a favorable milieu for growth of the WW strain of Theiler virus (TV). WW-TV induced a cytopathic effect characterized by neuronal destruction and swelling of myelin sheaths. Tissue culture medium and homogenates of infected cultures produced neurologic disease in mice, and TV was demonstrated in cultures by indirect immunofluorescence and electron microscopy. Ultrastructurally, severe alterations in neurons and the presence of cytoplasmic inclusions containing paracrystalline arrays of 30-nm virus particles were evident in astrocytes. Demyelination appeared to be secondary to lysis of oligodendrocytes by virus. CNS organotypic cultures provide an environment for the study of TV-induced demyelination.", "contents": "Growth of the WW strain of Theiler virus in mouse central nervous system organotypic culture. Myelinated organotypic cultures of mouse central nervous system (CNS) provide a favorable milieu for growth of the WW strain of Theiler virus (TV). WW-TV induced a cytopathic effect characterized by neuronal destruction and swelling of myelin sheaths. Tissue culture medium and homogenates of infected cultures produced neurologic disease in mice, and TV was demonstrated in cultures by indirect immunofluorescence and electron microscopy. Ultrastructurally, severe alterations in neurons and the presence of cytoplasmic inclusions containing paracrystalline arrays of 30-nm virus particles were evident in astrocytes. Demyelination appeared to be secondary to lysis of oligodendrocytes by virus. CNS organotypic cultures provide an environment for the study of TV-induced demyelination."}
{"id": "PMID:223368", "title": "Pexid-induced rat retinal pathology.", "content": "Three morphologically distinct kinds of cytoplasmic inclusion (lamellar, reticular and crystalloid) developed in the retinal cells of suckling rats treated with Pexid (300 mg/kg/day). Lamellar inclusions were most abundant and they were seen in all types of retinal cells. This variety of inclusion was especially numerous in the ganglion cells. Reticular inclusions were encountered less commonly than the lamellar type and their distribution did not show any particular cellular predilection. Crystalloid inclusions were observed only in the pigment epithelial cells. The mechanism of formation of the three types of inclusion is not known, nor is the reason why certain types of inclusion occur most commonly in a particular kind of cell. One can speculate, however, that the dissimilarity of form may reflect differences in the metabolism and physiochemical properties of the various retinal cells.", "contents": "Pexid-induced rat retinal pathology. Three morphologically distinct kinds of cytoplasmic inclusion (lamellar, reticular and crystalloid) developed in the retinal cells of suckling rats treated with Pexid (300 mg/kg/day). Lamellar inclusions were most abundant and they were seen in all types of retinal cells. This variety of inclusion was especially numerous in the ganglion cells. Reticular inclusions were encountered less commonly than the lamellar type and their distribution did not show any particular cellular predilection. Crystalloid inclusions were observed only in the pigment epithelial cells. The mechanism of formation of the three types of inclusion is not known, nor is the reason why certain types of inclusion occur most commonly in a particular kind of cell. One can speculate, however, that the dissimilarity of form may reflect differences in the metabolism and physiochemical properties of the various retinal cells."}
{"id": "PMID:223372", "title": "Screening for hyperlipoproteinemia in 10,000 Danish newborns. Follow-up studies in 522 children with elevated cord serum VLDL-LDL-cholesterol.", "content": "Among 10 440 newborns, 522 with upper 5 percentile values for very low-low density lipoprotein cholesterol in cord serum were selected for follow-up studies. Follow-up was possible in 446 of these 522 families (85%) and familial hypercholesterolemia (FH) was diagnosed in 11. In 273 of the 522 children, serum lipids were determined between the ages of 1 and 2 years and were now found to be normal, except in the 11 children with FH. Furthermore the serum lipids were compared in subgroups of these 273 children divided according to obstetric complications (i.e. low birth-weight, perinatal asphyxia and antepartum betamethasone treatment), which may cause a rise in serum lipids at birth. No differences were found between these subgroups at the age of 1--2 years.", "contents": "Screening for hyperlipoproteinemia in 10,000 Danish newborns. Follow-up studies in 522 children with elevated cord serum VLDL-LDL-cholesterol. Among 10 440 newborns, 522 with upper 5 percentile values for very low-low density lipoprotein cholesterol in cord serum were selected for follow-up studies. Follow-up was possible in 446 of these 522 families (85%) and familial hypercholesterolemia (FH) was diagnosed in 11. In 273 of the 522 children, serum lipids were determined between the ages of 1 and 2 years and were now found to be normal, except in the 11 children with FH. Furthermore the serum lipids were compared in subgroups of these 273 children divided according to obstetric complications (i.e. low birth-weight, perinatal asphyxia and antepartum betamethasone treatment), which may cause a rise in serum lipids at birth. No differences were found between these subgroups at the age of 1--2 years."}
{"id": "PMID:223374", "title": "Vitamin D sclerosis in rats.", "content": "The early fine structural changes in the arteries of rats induced by excess vitamin D3 perorally or parenterally were essentially similar, except the latter had a more prominent toxic effect to the vascular wall. The ultrastructural features, incidental to calcification, included the appearance of increased ground substance with a separation of collagenous and elastic fibrils, and degenerative changes in smooth muscle cells. Atherosclerosis was greatly accelerated at the sites of vascular injury when cholesterol, cholic acid and thiouracil were added to the basal diet. Calcification was initially observed in relation to elastic fibrils or degenerated cells in the upper and middle layers of the arteries, although there were few such deposits in the thickened intima of the coronary arteries. Calcium deposition could not be a direct effect of hypercalcemia, but the functional activity of smooth muscle cells did seem to promote the mineralization of calcium and phosphate. Furthermore, vitamin D-induced sclerosis did not prevent intimal thickening of the arteries when vitamin D3 was withdrawn.", "contents": "Vitamin D sclerosis in rats. The early fine structural changes in the arteries of rats induced by excess vitamin D3 perorally or parenterally were essentially similar, except the latter had a more prominent toxic effect to the vascular wall. The ultrastructural features, incidental to calcification, included the appearance of increased ground substance with a separation of collagenous and elastic fibrils, and degenerative changes in smooth muscle cells. Atherosclerosis was greatly accelerated at the sites of vascular injury when cholesterol, cholic acid and thiouracil were added to the basal diet. Calcification was initially observed in relation to elastic fibrils or degenerated cells in the upper and middle layers of the arteries, although there were few such deposits in the thickened intima of the coronary arteries. Calcium deposition could not be a direct effect of hypercalcemia, but the functional activity of smooth muscle cells did seem to promote the mineralization of calcium and phosphate. Furthermore, vitamin D-induced sclerosis did not prevent intimal thickening of the arteries when vitamin D3 was withdrawn."}
{"id": "PMID:223377", "title": "The effect of glucagon, dibutyrylic cyclic AMP and theophylline on bile production in the cat.", "content": "The effect of glucagon, dibutyrylic cyclic AMP and theophylline on bile production and liver metabolism was studied in fasting, chloralose anesthetized cats. After 45 min infusion of glucagon (0.1 mug/kg/min) total bile flow started to increase and finally reached a level 32% above control bile flow. The rise in flow was accompanied by a parallel increase in the biliary clearance of erythritol and the rate of biliary excretion of inorganic ions, whereas the bile acid excretion remained constant. Glucagon therefore appears to stimulate selectively the bile acid-independent canalicular production of bile. In contrast to the delayed action on bile production, glucagon caused an immediate change in liver metabolism as judged from the elimination rate of ethanol and the rise in plasma glucose concentration. Dibutyrylic cyclic AMP or theorphylline also caused similar immediate changes in liver metabolism but neither substance influenced bile production or the biliary excretion of electrolytes or bile acids. It thus appears that glucagon choleresis in the cat is either independent of cAMP release or that an increase in intracellular cAMP is not in itself sufficient to influence bile secretion. The results also seem to exclude that an increase in insulin production induced by hyperglycemia, or hemodynamic changes in the liver, can explain glucagon choleresis.", "contents": "The effect of glucagon, dibutyrylic cyclic AMP and theophylline on bile production in the cat. The effect of glucagon, dibutyrylic cyclic AMP and theophylline on bile production and liver metabolism was studied in fasting, chloralose anesthetized cats. After 45 min infusion of glucagon (0.1 mug/kg/min) total bile flow started to increase and finally reached a level 32% above control bile flow. The rise in flow was accompanied by a parallel increase in the biliary clearance of erythritol and the rate of biliary excretion of inorganic ions, whereas the bile acid excretion remained constant. Glucagon therefore appears to stimulate selectively the bile acid-independent canalicular production of bile. In contrast to the delayed action on bile production, glucagon caused an immediate change in liver metabolism as judged from the elimination rate of ethanol and the rise in plasma glucose concentration. Dibutyrylic cyclic AMP or theorphylline also caused similar immediate changes in liver metabolism but neither substance influenced bile production or the biliary excretion of electrolytes or bile acids. It thus appears that glucagon choleresis in the cat is either independent of cAMP release or that an increase in intracellular cAMP is not in itself sufficient to influence bile secretion. The results also seem to exclude that an increase in insulin production induced by hyperglycemia, or hemodynamic changes in the liver, can explain glucagon choleresis."}
{"id": "PMID:223378", "title": "Adenylate kinase activity in cerebrospinal fluid of schizophrenic and certain other psychiatric symptomatologies.", "content": "Adenylate kinase activity in the cerebrospinal fluid (CSF) was investigated in 29 patients with psychiatric symptomatologies. Such activity was demonstrated in 18 of the 19 individuals with schizophrenic or other psychotic or borderline psychotic symptomatology. No activity was seen in the remaining 10 patients with non-psychotic nervous and/or functional somatic complaints, nor in the 20 persons whose CSF was examined in connection with spinal anaesthesia, nor in four who were treated with neuroleptic drugs on nonpsychiatric indications. The findings are compatible with the assumption that in persons with psychotic or borderline psychotic symptomatology a lowered membrane electrochemical potential may be associated with some of the symptoms exhibited.", "contents": "Adenylate kinase activity in cerebrospinal fluid of schizophrenic and certain other psychiatric symptomatologies. Adenylate kinase activity in the cerebrospinal fluid (CSF) was investigated in 29 patients with psychiatric symptomatologies. Such activity was demonstrated in 18 of the 19 individuals with schizophrenic or other psychotic or borderline psychotic symptomatology. No activity was seen in the remaining 10 patients with non-psychotic nervous and/or functional somatic complaints, nor in the 20 persons whose CSF was examined in connection with spinal anaesthesia, nor in four who were treated with neuroleptic drugs on nonpsychiatric indications. The findings are compatible with the assumption that in persons with psychotic or borderline psychotic symptomatology a lowered membrane electrochemical potential may be associated with some of the symptoms exhibited."}
{"id": "PMID:223375", "title": "Comparison of the mechanism of action of vitamin D3 and 1 alpha-OH D3 under conditions of experimental hypercalcemia.", "content": "Comparison of the mechanism of action Vitamin D3 and 1 alpha-OH D3 under conditions of experimental hypercalcemia. Acta Physiol. Pol. 1979, 30 (2): 313--318. The hypercalcemic effect of supraphysiological doses of Vitamin D and 1 alpha-OH D3 were compared applying an animal model. Changes in serum calcium of animals with normal dietary calcium supplementation and those under conditions of calcium depletion were analyzed. Dietary calcium is necessary for the hypercalcemic effect of Vitamin D, whereas in case of 1 alpha-OH D3 calcium is mobilized not only from the dietary but also from some other sources. The analysis of the hypercalcemia kinetics in the Vitamin D and 1 alpha-OH D3 treated animals indicated that the kidney 1 hydroxylase of 25 hydroxycholecalciferol is an important step in the hypercalcemia preventing mechanism.", "contents": "Comparison of the mechanism of action of vitamin D3 and 1 alpha-OH D3 under conditions of experimental hypercalcemia. Comparison of the mechanism of action Vitamin D3 and 1 alpha-OH D3 under conditions of experimental hypercalcemia. Acta Physiol. Pol. 1979, 30 (2): 313--318. The hypercalcemic effect of supraphysiological doses of Vitamin D and 1 alpha-OH D3 were compared applying an animal model. Changes in serum calcium of animals with normal dietary calcium supplementation and those under conditions of calcium depletion were analyzed. Dietary calcium is necessary for the hypercalcemic effect of Vitamin D, whereas in case of 1 alpha-OH D3 calcium is mobilized not only from the dietary but also from some other sources. The analysis of the hypercalcemia kinetics in the Vitamin D and 1 alpha-OH D3 treated animals indicated that the kidney 1 hydroxylase of 25 hydroxycholecalciferol is an important step in the hypercalcemia preventing mechanism."}
{"id": "PMID:223381", "title": "Follicular growth in the rat: a reevaluation of the roles of FSH and LH.", "content": "The growth of preovulatory ovarian follicles involves hormonally induced proliferation and differentiation of theca cells and granulosa cells resulting ultimately in an increased ability of follicles to produce estradiol and to respond to the pituitary gonadotropins. The increased ability of follicles to produce estradiol appears to depend on an increased ability of theca cells to produce androgen as well as an increased ability of granulosa cells to aromatize androgens to estradiol. Estradiol in turn, appears to be required for FSH or FSH and LH to stimulate the appearance of functional receptors for LH in granulosa cells. Thus, the intrafollicular hormone estradiol enhances the response of granulosa cells to the gonadotropin. Therefore production of estradiol appears to determine which follicles will gain the mechanisms, including LH receptor, necessary for ovulation and luteinization. Since LH can act to increase its own receptor in the presence of estradiol and low amounts of FSH, it is possible that LH plays a predominant role in the final stages of preovulatory follicular growth both to promote estradiol production stimulation of theca cell androgen production as well as by facilitating an increase in its receptor by acting directly on granulosa cells.", "contents": "Follicular growth in the rat: a reevaluation of the roles of FSH and LH. The growth of preovulatory ovarian follicles involves hormonally induced proliferation and differentiation of theca cells and granulosa cells resulting ultimately in an increased ability of follicles to produce estradiol and to respond to the pituitary gonadotropins. The increased ability of follicles to produce estradiol appears to depend on an increased ability of theca cells to produce androgen as well as an increased ability of granulosa cells to aromatize androgens to estradiol. Estradiol in turn, appears to be required for FSH or FSH and LH to stimulate the appearance of functional receptors for LH in granulosa cells. Thus, the intrafollicular hormone estradiol enhances the response of granulosa cells to the gonadotropin. Therefore production of estradiol appears to determine which follicles will gain the mechanisms, including LH receptor, necessary for ovulation and luteinization. Since LH can act to increase its own receptor in the presence of estradiol and low amounts of FSH, it is possible that LH plays a predominant role in the final stages of preovulatory follicular growth both to promote estradiol production stimulation of theca cell androgen production as well as by facilitating an increase in its receptor by acting directly on granulosa cells."}
{"id": "PMID:223385", "title": "Steroidal modulation of steroid secretion in vitro: an experimental approach to intra-follicular regulatory mechanisms.", "content": "Studies in vitro and in vivo indicate that steroid secretion by granulosa cells of the developing follicle is modulated in part by steroid hormones themselves. Androgens stimulate progestin synthesis in vitro by granulosa cells of all developmental stages independently of their role as an estrogen precursor; generally, the action of estradiol results in suppression of progesterone secretion. The nature of the relationship between steroid secretion by granulosa cells and the physiological processes of follicular development or atresia remains to be investigated in greater detail. The cellular mechanism(s) of steroidal modulation of steroid secretion is unknown but apparently does not involve changes in the number of granulosa cell LH receptors per se.", "contents": "Steroidal modulation of steroid secretion in vitro: an experimental approach to intra-follicular regulatory mechanisms. Studies in vitro and in vivo indicate that steroid secretion by granulosa cells of the developing follicle is modulated in part by steroid hormones themselves. Androgens stimulate progestin synthesis in vitro by granulosa cells of all developmental stages independently of their role as an estrogen precursor; generally, the action of estradiol results in suppression of progesterone secretion. The nature of the relationship between steroid secretion by granulosa cells and the physiological processes of follicular development or atresia remains to be investigated in greater detail. The cellular mechanism(s) of steroidal modulation of steroid secretion is unknown but apparently does not involve changes in the number of granulosa cell LH receptors per se."}
{"id": "PMID:223376", "title": "The influence of sodium diethyldithiocarbamate (DDC) on serum lipids in the rabbit.", "content": "The influence of sodium diethyldithiocarbamate (DDC) on serum lipids in the rabbit. Acta Physiol. Pol., 1979, 30 (2): 327--329. The level of cholesterol, phospholipids and triglycerides in blood serum of rabbits treated with sodium diethyldithiocarbamate (DDC) was determined. DDC administration in daily doses of 100, 200 and 400 mg/kg, during 4 weeks, resulted in an increase of triglyceride and phospholipid levels changes were found in the serum cholesterol concentration.", "contents": "The influence of sodium diethyldithiocarbamate (DDC) on serum lipids in the rabbit. The influence of sodium diethyldithiocarbamate (DDC) on serum lipids in the rabbit. Acta Physiol. Pol., 1979, 30 (2): 327--329. The level of cholesterol, phospholipids and triglycerides in blood serum of rabbits treated with sodium diethyldithiocarbamate (DDC) was determined. DDC administration in daily doses of 100, 200 and 400 mg/kg, during 4 weeks, resulted in an increase of triglyceride and phospholipid levels changes were found in the serum cholesterol concentration."}
{"id": "PMID:223389", "title": "Mammalian oocyte maturation: model systems and their physiological relevance.", "content": "Maturation of mammalian oocytes is studied mainly in two dissimilar in vitro models: isolated oocytes maturing spontaneously in culture, and hormone-induced maturation of follicle-enclosed oocytes. In this discussion the following aspects of maturation in vitro in the two aforementioned models were compared: timing of germinal vesicle breakdown (GVB), involvement of cyclic nucleotides, protein synthesis and divalent cations. A third approach to the study of oocyte maturation in vitro, namely oocyte co-culture with follicular constituents was adopted in order to test the role of follicular components in the control of the resumption of meiosis. Such studies demonstrated an inhibitory action of granulosa cells, granulosa cell-conditioned medium and of follicular fluid upon the spontaneous maturation of the co-cultured oocytes. Furthermore, addition of LH to co-cultures of oocytes and granulosa cells induced resumption of meiosis. Although oocytes obtained by spontaneous or by hormone-induced maturation cannot be distinguished morphologically, the developmental potential of oocytes matured spontaneously has been questioned, at least in some species. Furthermore, analysis of the kinetics of spontaneous maturation suggests that oocytes dislodged from their follicles escape physiologic mechanisms ensuring meiotic arrest and skip some of the regulatory steps involved in the normal hormonal triggering of maturation. Oocyte co-culture with granulosa cells offers a close approximation to physiological conditions in that meiotic maturation depends on hormonal stimulation, while the system permits the application of separate treatments to the oocyte-cumulus complex and granulosa cells. As in any in vitro system, critical evaluation is required to discriminate between artifacts inherent in the model and physiological processes.", "contents": "Mammalian oocyte maturation: model systems and their physiological relevance. Maturation of mammalian oocytes is studied mainly in two dissimilar in vitro models: isolated oocytes maturing spontaneously in culture, and hormone-induced maturation of follicle-enclosed oocytes. In this discussion the following aspects of maturation in vitro in the two aforementioned models were compared: timing of germinal vesicle breakdown (GVB), involvement of cyclic nucleotides, protein synthesis and divalent cations. A third approach to the study of oocyte maturation in vitro, namely oocyte co-culture with follicular constituents was adopted in order to test the role of follicular components in the control of the resumption of meiosis. Such studies demonstrated an inhibitory action of granulosa cells, granulosa cell-conditioned medium and of follicular fluid upon the spontaneous maturation of the co-cultured oocytes. Furthermore, addition of LH to co-cultures of oocytes and granulosa cells induced resumption of meiosis. Although oocytes obtained by spontaneous or by hormone-induced maturation cannot be distinguished morphologically, the developmental potential of oocytes matured spontaneously has been questioned, at least in some species. Furthermore, analysis of the kinetics of spontaneous maturation suggests that oocytes dislodged from their follicles escape physiologic mechanisms ensuring meiotic arrest and skip some of the regulatory steps involved in the normal hormonal triggering of maturation. Oocyte co-culture with granulosa cells offers a close approximation to physiological conditions in that meiotic maturation depends on hormonal stimulation, while the system permits the application of separate treatments to the oocyte-cumulus complex and granulosa cells. As in any in vitro system, critical evaluation is required to discriminate between artifacts inherent in the model and physiological processes."}
{"id": "PMID:223390", "title": "LH-induced desensitization of the adenylyl cyclase system in ovarian follicles.", "content": "Studies on the gonadotrophin-responsive adenylyl cyclase (AC) system of rabbit and porcine ovarian follicles reveal that hCG or LH-induced desensitization of the AC system can be divided into two phases: an initial, LH-specific phase and a second phase which is not specific for LH. The first phase occurs within the first hour after LH-hCG-receptor interaction, is agonist specific, and is not mediated by protein synthetic events or by cAMP. In view of our previous demonstration of the critical dependence of the LH-induced desensitizing process in cell-free membrane preparations of porcine follicles upon Mg2+ and ATP, we investigated the role of a phosphorylation reaction in the first phase of the AC desensitizing process. Porcine follicular membranes rich in LH-sensitive AC activity were found to contain the molecular requirements necessary for a phosphorylation reaction: namely, cAMP-dependent and cAMP-independent protein kinases as well as phosphoprotein phosphatases. The following lines of indirect evidence indicated that reversal or resensitization of the desenzitized AC system to LH was mediated by a dephosphorylation reaction. Activators of endogenous phosphoprotein phosphatases--Mn2+ and dithiothreitol--promoted a specific resensitization of the follicular AC system to LH. Likewise, a partially purified phosphoprotein phosphatase also resensitized the desensitized, LH unresponsive AC to LH, and boiling of the phosphatase prevented its effect. LH-induced desensitization of the AC system, on the other hand, did not appear to be mediated by a cAMP-dependent protein kinase, as evidenced both by the inability of beef heart protein to promote desensitization of AC and by the inability of an inhibitor of cAMP-dependent protein kinase to prevent LH-induced densensitization. The second phase of desensitization, which occurs after the first hour following hCG-LH-receptor interaction, is characterized by a loss of responsiveness to FSH as well as to LH and can be promoted by dibutryl cAMP (in the absence of LH). These results provide new evidence on the characteristics and molecular mechanism of LH-induced densensitization of the follicular AC system. These results indicate that the level of phosphorylation of membrane-associated components may, in part, regulate the activity of the AC system during this first phase of homologous desensitization.", "contents": "LH-induced desensitization of the adenylyl cyclase system in ovarian follicles. Studies on the gonadotrophin-responsive adenylyl cyclase (AC) system of rabbit and porcine ovarian follicles reveal that hCG or LH-induced desensitization of the AC system can be divided into two phases: an initial, LH-specific phase and a second phase which is not specific for LH. The first phase occurs within the first hour after LH-hCG-receptor interaction, is agonist specific, and is not mediated by protein synthetic events or by cAMP. In view of our previous demonstration of the critical dependence of the LH-induced desensitizing process in cell-free membrane preparations of porcine follicles upon Mg2+ and ATP, we investigated the role of a phosphorylation reaction in the first phase of the AC desensitizing process. Porcine follicular membranes rich in LH-sensitive AC activity were found to contain the molecular requirements necessary for a phosphorylation reaction: namely, cAMP-dependent and cAMP-independent protein kinases as well as phosphoprotein phosphatases. The following lines of indirect evidence indicated that reversal or resensitization of the desenzitized AC system to LH was mediated by a dephosphorylation reaction. Activators of endogenous phosphoprotein phosphatases--Mn2+ and dithiothreitol--promoted a specific resensitization of the follicular AC system to LH. Likewise, a partially purified phosphoprotein phosphatase also resensitized the desensitized, LH unresponsive AC to LH, and boiling of the phosphatase prevented its effect. LH-induced desensitization of the AC system, on the other hand, did not appear to be mediated by a cAMP-dependent protein kinase, as evidenced both by the inability of beef heart protein to promote desensitization of AC and by the inability of an inhibitor of cAMP-dependent protein kinase to prevent LH-induced densensitization. The second phase of desensitization, which occurs after the first hour following hCG-LH-receptor interaction, is characterized by a loss of responsiveness to FSH as well as to LH and can be promoted by dibutryl cAMP (in the absence of LH). These results provide new evidence on the characteristics and molecular mechanism of LH-induced densensitization of the follicular AC system. These results indicate that the level of phosphorylation of membrane-associated components may, in part, regulate the activity of the AC system during this first phase of homologous desensitization."}
{"id": "PMID:223398", "title": "Mechanisms of PGF2 alpha action in functional luteolysis.", "content": "The luteolytic action of PGF2 alpha appears to be due to loss of gonadotropin support of corpus luteum function. This \"chemical hypophysectomy\" produced by PGF2 alpha in the rat has several components: 1. A rapid block of gonadotropin uptake in vivo by an unexplained mechanism. 2. A rapid and direct block of adenylate cyclase activation by the LH receptor complex in isolated luteal cells. 3. An eventual loss of LH receptor binding activity produced by inhibition of prolactin action.", "contents": "Mechanisms of PGF2 alpha action in functional luteolysis. The luteolytic action of PGF2 alpha appears to be due to loss of gonadotropin support of corpus luteum function. This \"chemical hypophysectomy\" produced by PGF2 alpha in the rat has several components: 1. A rapid block of gonadotropin uptake in vivo by an unexplained mechanism. 2. A rapid and direct block of adenylate cyclase activation by the LH receptor complex in isolated luteal cells. 3. An eventual loss of LH receptor binding activity produced by inhibition of prolactin action."}
{"id": "PMID:223409", "title": "hCG-induced loss of LH-hCG receptor and desensitization of adenylate cyclase.", "content": "hCG-induced loss of hCG (LH) receptors and desensitization of adenylate cyclase in the pseudopregnant rat ovary have been studied. At various time intervals after hCG treatment, the decrease in hCG-stimulated adenylate cyclase activity was closely related to the reduction in available hCG receptors. The hCG-induced desensitization of adenylate cyclase and a fall in hCG binding activity were also dose-dependent and directly correlated. There were no changes in the affinity of receptors binding and in the apparent Km for adenylate cyclase activation. These findings indicate that the loss of hCG receptors is associated with desensitization of adenylate cyclase following the hCG injection.", "contents": "hCG-induced loss of LH-hCG receptor and desensitization of adenylate cyclase. hCG-induced loss of hCG (LH) receptors and desensitization of adenylate cyclase in the pseudopregnant rat ovary have been studied. At various time intervals after hCG treatment, the decrease in hCG-stimulated adenylate cyclase activity was closely related to the reduction in available hCG receptors. The hCG-induced desensitization of adenylate cyclase and a fall in hCG binding activity were also dose-dependent and directly correlated. There were no changes in the affinity of receptors binding and in the apparent Km for adenylate cyclase activation. These findings indicate that the loss of hCG receptors is associated with desensitization of adenylate cyclase following the hCG injection."}
{"id": "PMID:223410", "title": "Evidence of a greater activity of LH/HCH binding inhibitor present in aqueous extracts from old compared to young porcine corpus luteum.", "content": "As porcine corpus luteum tissue ages there is an increase in amount of LH/hCG vinding inhibitor. This inhibitor is absent in non-luteal ovarian tissue, heart and lung.", "contents": "Evidence of a greater activity of LH/HCH binding inhibitor present in aqueous extracts from old compared to young porcine corpus luteum. As porcine corpus luteum tissue ages there is an increase in amount of LH/hCG vinding inhibitor. This inhibitor is absent in non-luteal ovarian tissue, heart and lung."}
{"id": "PMID:223411", "title": "Suppression of ovarian function by LHRH and its analogues in pregnant rats.", "content": "1. LHRH and its analogues, when infused continuously at the doses that inhibit ovum implantation, reduced serum concentration of progesterone in pregnant rats. The progesterone concentration fell between Days 3 and 4 of pregnancy in rats treated with LHRH and Analogue I (Des-Gly10-LHRH-ethylamide), but fell between Days 4 and 5 in rats treated with Analogue II [Des-Gly10-(D-Ala6)-LHRH-ethylamide]. 2. Ovarian LH/hCG receptor levels were markedly reduced in rats treated with LHRH and its analogues in the first week of pregnancy. 3. Continuous infusion of LH to pregnant rats did not reduce the serum concentration of progesterone even with the highest dose that inhibited implantation. Interruption of pregnancy by LH appears to be due to excessive secretion of estrogen as indicated by uterine swellings, presence of large follicles in the ovaries, and absence of free blastocysts in the uterine lumen. Thus, the antifertility effects of LHRH and its analogues were not reproduced by LH administration.", "contents": "Suppression of ovarian function by LHRH and its analogues in pregnant rats. 1. LHRH and its analogues, when infused continuously at the doses that inhibit ovum implantation, reduced serum concentration of progesterone in pregnant rats. The progesterone concentration fell between Days 3 and 4 of pregnancy in rats treated with LHRH and Analogue I (Des-Gly10-LHRH-ethylamide), but fell between Days 4 and 5 in rats treated with Analogue II [Des-Gly10-(D-Ala6)-LHRH-ethylamide]. 2. Ovarian LH/hCG receptor levels were markedly reduced in rats treated with LHRH and its analogues in the first week of pregnancy. 3. Continuous infusion of LH to pregnant rats did not reduce the serum concentration of progesterone even with the highest dose that inhibited implantation. Interruption of pregnancy by LH appears to be due to excessive secretion of estrogen as indicated by uterine swellings, presence of large follicles in the ovaries, and absence of free blastocysts in the uterine lumen. Thus, the antifertility effects of LHRH and its analogues were not reproduced by LH administration."}
{"id": "PMID:223412", "title": "Clinical applications in the area of contraceptive development.", "content": "The ovary is not necessarily a prime locus for regulating reproductive function but in the process of understanding various aspects of ovarian function, opportunities have arisen to test both the role of specific functions in the reproductive process and the possible use of a given function as a site for contraceptive regulation. Better understanding of corpus luteum physiology from receptor site-gonadotropin interaction to natural luteolytic processes still hold promise for contraceptive development.", "contents": "Clinical applications in the area of contraceptive development. The ovary is not necessarily a prime locus for regulating reproductive function but in the process of understanding various aspects of ovarian function, opportunities have arisen to test both the role of specific functions in the reproductive process and the possible use of a given function as a site for contraceptive regulation. Better understanding of corpus luteum physiology from receptor site-gonadotropin interaction to natural luteolytic processes still hold promise for contraceptive development."}
{"id": "PMID:223421", "title": "Hypothermia-induced potentiation of histamine H2-receptor-mediated relaxation and cyclic AMP increase in the isolated mesenteric artery of the rabbit.", "content": "On helically cut strips of the rabbit's mesenteric artery, a temperature decrease from 42 degrees C to 25 degrees C reduced the contractile responses to histamine. Metiamide shifted the dose-response curve of the histamine-induced contraction towards higher values at 25 degrees C, but not at 42 degrees C. Furthermore, on arterial strips contracted by phenylephrine histamine evoked a dose-dependent relaxation at 25 degrees C whereas at 42 degrees C only slight relaxing responses to histamine occurred. Metiamide was capable of preventing the relaxation induced by histamine in a competitive manner. At 25 degrees C the relaxation as produced by histamine was accompanied by increases in cyclic AMP which occurred prior to the relaxing effects. Metiamide abolished the cyclic AMP increase in response to histamine. At 42 degrees C histamine was unable to elevate the cyclic AMP content. Thus, it is concluded that a cyclic AMP-mediated relaxation due to stimulation of H2-receptors counteracts the histamine-induced contraction and reduces the contractile responses to histamine at low temperatures. In addition, clear-cut evidence exists from the present study that also on artery smooth muscle the H2-receptor-mediated responses are closely associated to cyclic AMP.", "contents": "Hypothermia-induced potentiation of histamine H2-receptor-mediated relaxation and cyclic AMP increase in the isolated mesenteric artery of the rabbit. On helically cut strips of the rabbit's mesenteric artery, a temperature decrease from 42 degrees C to 25 degrees C reduced the contractile responses to histamine. Metiamide shifted the dose-response curve of the histamine-induced contraction towards higher values at 25 degrees C, but not at 42 degrees C. Furthermore, on arterial strips contracted by phenylephrine histamine evoked a dose-dependent relaxation at 25 degrees C whereas at 42 degrees C only slight relaxing responses to histamine occurred. Metiamide was capable of preventing the relaxation induced by histamine in a competitive manner. At 25 degrees C the relaxation as produced by histamine was accompanied by increases in cyclic AMP which occurred prior to the relaxing effects. Metiamide abolished the cyclic AMP increase in response to histamine. At 42 degrees C histamine was unable to elevate the cyclic AMP content. Thus, it is concluded that a cyclic AMP-mediated relaxation due to stimulation of H2-receptors counteracts the histamine-induced contraction and reduces the contractile responses to histamine at low temperatures. In addition, clear-cut evidence exists from the present study that also on artery smooth muscle the H2-receptor-mediated responses are closely associated to cyclic AMP."}
{"id": "PMID:223422", "title": "Skeletal effects of megavoltage irradiation in survivors of Wilms' tumor.", "content": "The skeletal effects of megavoltage irradiation (60Co) in 25 long term survivors of Wilms' tumor are described. In general, the changes seen with megavoltage irradiation are as frequent but not as severe as those previously reported after orthovoltage irradiation. Vertebral body changes generally occur within 5 years after irradiation. Scoliosis and/or kyphosis do not usually develop until after five years postirradiation. Kyphotic curves tend to progress after the adolescent growth spurt while scoliotic curves do not. Other bony and nonosseous changes are detailed.", "contents": "Skeletal effects of megavoltage irradiation in survivors of Wilms' tumor. The skeletal effects of megavoltage irradiation (60Co) in 25 long term survivors of Wilms' tumor are described. In general, the changes seen with megavoltage irradiation are as frequent but not as severe as those previously reported after orthovoltage irradiation. Vertebral body changes generally occur within 5 years after irradiation. Scoliosis and/or kyphosis do not usually develop until after five years postirradiation. Kyphotic curves tend to progress after the adolescent growth spurt while scoliotic curves do not. Other bony and nonosseous changes are detailed."}
{"id": "PMID:223423", "title": "Radiology of epidemic adenovirus 21 infection of the lower respiratory tract in infants and young children.", "content": "The radiologic features of 18 children admitted to Princess Mary Hospital, Auckland, New Zealand, in the winter and spring of 1977 with adenovirus 21 infection are reported. Attention is drawn to the severity of the disease in the respiratory tract, manifest radiologically as widespread patchy or confluent pulmonary opacification, extensive bronchial wall thickening, or peribronchial linear opacities. No hilar adenopathy was present. Prominent residual bronchopulmonary abnormalities were present in 13 of 15 patients 6--12 months after epidemic. High kilovoltage chester radiography or bronchography demonstrated bronchiectasis in five patients. These findings emphasize the role of adenovirus as a cause of chronic pulmonary disease and bronchiectasis in children.", "contents": "Radiology of epidemic adenovirus 21 infection of the lower respiratory tract in infants and young children. The radiologic features of 18 children admitted to Princess Mary Hospital, Auckland, New Zealand, in the winter and spring of 1977 with adenovirus 21 infection are reported. Attention is drawn to the severity of the disease in the respiratory tract, manifest radiologically as widespread patchy or confluent pulmonary opacification, extensive bronchial wall thickening, or peribronchial linear opacities. No hilar adenopathy was present. Prominent residual bronchopulmonary abnormalities were present in 13 of 15 patients 6--12 months after epidemic. High kilovoltage chester radiography or bronchography demonstrated bronchiectasis in five patients. These findings emphasize the role of adenovirus as a cause of chronic pulmonary disease and bronchiectasis in children."}
{"id": "PMID:223424", "title": "Size and skeletal maturation of the hand in children with hypothyroidism and hypopituitarism.", "content": "Hypothyroidism affects linear growth less than it affects skeletal maturation, while hypopituitarism linear growth is more severely affected. By determining the mean age for the length of the second metacarpal and dividing by the skeletal age, a ratio R was obtained in 15 hypothyroid children and in 33 with hypopituitarism. R was more than 1 in most hypothyroids and less than 1 in most children with hypopituitarism. Thus, a distinction between these two entities can be made simply from a hand radiograph and appropriate reference sources for determining second metacarpal length age and skeletal age.", "contents": "Size and skeletal maturation of the hand in children with hypothyroidism and hypopituitarism. Hypothyroidism affects linear growth less than it affects skeletal maturation, while hypopituitarism linear growth is more severely affected. By determining the mean age for the length of the second metacarpal and dividing by the skeletal age, a ratio R was obtained in 15 hypothyroid children and in 33 with hypopituitarism. R was more than 1 in most hypothyroids and less than 1 in most children with hypopituitarism. Thus, a distinction between these two entities can be made simply from a hand radiograph and appropriate reference sources for determining second metacarpal length age and skeletal age."}
{"id": "PMID:223427", "title": "Two dimensional echocardiographic quantification of infarct size alteration by pharmacologic agents.", "content": "In 27 closed chest dogs left ventricular wall motion abnormalities assessed quantitatively with two dimensional echocardiography were used as a measure of myocardial infarct size, and the change in extent of segmental wall motion abnormalities due to drug intervention early after infarction was evaluated. The extent of wall motion abnormalities was measured with echocardiography before and at 20 and 40 minutes and 5 1/2 hours after coronary occlusion. Three subgroups of dogs received, respectively, an infusion of nitroglycerin, phenylephrine or saline solution. Infarct size was measured with technetium pyrophosphate scintigraphy of the excised left ventricle. The infarct size correlated well with the extent of wall motion abnormalities before death. Wall motion was initially similar among the three groups but was significantly improved after treatment with nitroglycerin (P less than 0.025), remained stable with continued saline infusion and worsened significantly (P less than 0.05) after treatment with phenylephrine. Two dimensional echocardiography can be used to quantify experimental canine myocardial infarction and assess the effect of nitroglycerin.", "contents": "Two dimensional echocardiographic quantification of infarct size alteration by pharmacologic agents. In 27 closed chest dogs left ventricular wall motion abnormalities assessed quantitatively with two dimensional echocardiography were used as a measure of myocardial infarct size, and the change in extent of segmental wall motion abnormalities due to drug intervention early after infarction was evaluated. The extent of wall motion abnormalities was measured with echocardiography before and at 20 and 40 minutes and 5 1/2 hours after coronary occlusion. Three subgroups of dogs received, respectively, an infusion of nitroglycerin, phenylephrine or saline solution. Infarct size was measured with technetium pyrophosphate scintigraphy of the excised left ventricle. The infarct size correlated well with the extent of wall motion abnormalities before death. Wall motion was initially similar among the three groups but was significantly improved after treatment with nitroglycerin (P less than 0.025), remained stable with continued saline infusion and worsened significantly (P less than 0.05) after treatment with phenylephrine. Two dimensional echocardiography can be used to quantify experimental canine myocardial infarction and assess the effect of nitroglycerin."}
{"id": "PMID:223428", "title": "Epicardial ischemia as delineated with epicardial S-T segment mapping andnicotinamide adenine dinucleotide (NADH) fluorescence photography.", "content": "In isolated rabbit hearts with an experimental coronary arterial occlusion, epicardial ischemia was identified by reduced nicotinamide adenine dinucleotide (NADH) fluorescence photography, a technique that detects areas of myocardial anoxia. Epicardial S-T segment mapping was performed to evaluate the S-T segment changes across an ischemic border defined by NADH fluorescence. After S-T segment mapping and perfusion with a fluorescein dye, serial selections of the hearts revealed that the ischemic area was transmural and and the border was nearly perpendicular to the epicardial surface. As the epicardial ischemic border was approached, S-T segment elevation was first detected 3.3 mm outside the ischemic border, and increased over a transition zone 7 mm wide. S-T segment negativity was not detected immediately outside the ischemic border. It is concluded from these studies that S-T segment changes give relatively imprecise definition of an ischemic border, and that S-T segment changes across an ischemic border are not consistent with those predicted by solid angle analysis.", "contents": "Epicardial ischemia as delineated with epicardial S-T segment mapping andnicotinamide adenine dinucleotide (NADH) fluorescence photography. In isolated rabbit hearts with an experimental coronary arterial occlusion, epicardial ischemia was identified by reduced nicotinamide adenine dinucleotide (NADH) fluorescence photography, a technique that detects areas of myocardial anoxia. Epicardial S-T segment mapping was performed to evaluate the S-T segment changes across an ischemic border defined by NADH fluorescence. After S-T segment mapping and perfusion with a fluorescein dye, serial selections of the hearts revealed that the ischemic area was transmural and and the border was nearly perpendicular to the epicardial surface. As the epicardial ischemic border was approached, S-T segment elevation was first detected 3.3 mm outside the ischemic border, and increased over a transition zone 7 mm wide. S-T segment negativity was not detected immediately outside the ischemic border. It is concluded from these studies that S-T segment changes give relatively imprecise definition of an ischemic border, and that S-T segment changes across an ischemic border are not consistent with those predicted by solid angle analysis."}
{"id": "PMID:223429", "title": "Immunocytochemical evidence for anti-LHRH and anti-ACTH activity in the \"F\" antiserum.", "content": "An antiserum which has previously been thought to be specific for LHRH-like immunoreactive material was shown to contain two populations of antibodies, one demonstrating anti-LHRH activity and the other anti-ACTH(1-24) activity. In rat and mouse, ACTH(1-24)-like immunoreactive substance is present in perikarya within the basal hypothalamus and in fibers in arcuate, periventricular and dorsomedial nuclei. LHRH-like immunoreactivity is present in fibers within the median eminence and arcuate nucleus, in a few fibers running along the ventral border of the hypothalamus, and in a small number of cell bodies within the medial basal hypothalamus.", "contents": "Immunocytochemical evidence for anti-LHRH and anti-ACTH activity in the \"F\" antiserum. An antiserum which has previously been thought to be specific for LHRH-like immunoreactive material was shown to contain two populations of antibodies, one demonstrating anti-LHRH activity and the other anti-ACTH(1-24) activity. In rat and mouse, ACTH(1-24)-like immunoreactive substance is present in perikarya within the basal hypothalamus and in fibers in arcuate, periventricular and dorsomedial nuclei. LHRH-like immunoreactivity is present in fibers within the median eminence and arcuate nucleus, in a few fibers running along the ventral border of the hypothalamus, and in a small number of cell bodies within the medial basal hypothalamus."}
{"id": "PMID:223431", "title": "Height, weight, and head circumference in survivors of marasmus and kwashiorkor.", "content": "The physical growth of 44 survivors of marasmus and 43 survivors of kwashiorker 7 1/2 years after their hospitalization and cure from malnutrition has been evaluated. The collected data on height, weight, and head circumference of these 87 previously malnourished children have been compared with data on height, weight, and head circumference of 559 children of the same age and sex from the same environment who have never been malnourished. The statistical analysis of the data indicate the following conclusions. 1) The survivors of marasmus are shorter and lighter and have a smaller head circumference than controls. The observed difference is statistically significant. 2) The survivors of kwashiorkor have the same physical stature as controls. 3) The survivors of marasmus are shorter and lighter and have a smaller head circumference than survivors of kwashiorkor. 4) The survivors of marasmus who were hospitalized for treatment of malnutrition when younger than 1 year have the same physical stature as the survivors of marasmus who were hospitalized for treatment of malnutrition when older than 1 year.", "contents": "Height, weight, and head circumference in survivors of marasmus and kwashiorkor. The physical growth of 44 survivors of marasmus and 43 survivors of kwashiorker 7 1/2 years after their hospitalization and cure from malnutrition has been evaluated. The collected data on height, weight, and head circumference of these 87 previously malnourished children have been compared with data on height, weight, and head circumference of 559 children of the same age and sex from the same environment who have never been malnourished. The statistical analysis of the data indicate the following conclusions. 1) The survivors of marasmus are shorter and lighter and have a smaller head circumference than controls. The observed difference is statistically significant. 2) The survivors of kwashiorkor have the same physical stature as controls. 3) The survivors of marasmus are shorter and lighter and have a smaller head circumference than survivors of kwashiorkor. 4) The survivors of marasmus who were hospitalized for treatment of malnutrition when younger than 1 year have the same physical stature as the survivors of marasmus who were hospitalized for treatment of malnutrition when older than 1 year."}
{"id": "PMID:223425", "title": "[Action of repeated doses of a beta-adrenergic in the response of plasma cyclic AMP in asthmatic patients].", "content": "The present work studies the behaviour of plasma cAMP after repeated doses of a beta mimetic currently used as a broncodilator in asthmatics. A group of patients repeatedly treated with Phenoterol showed increased cAMP values, particularly evident when compared with those obtained throughout the day. It is notable that this increase does not continue with treatment, but levels off and even shows some tendency to diminish. After the final dose of beta mimetic there is an abrupt fall of cAMP to initial (pre-treatment) values. It is suggested that the increase in nucleotide values is not maintained after repeated doses of beta-stimulants because asthmatics show a diminished response as a result of exhaustion or \"tolerance\" to the response. It is probable that, as in the case of some hormones, the receptors in the effector organs are exhausted.", "contents": "[Action of repeated doses of a beta-adrenergic in the response of plasma cyclic AMP in asthmatic patients]. The present work studies the behaviour of plasma cAMP after repeated doses of a beta mimetic currently used as a broncodilator in asthmatics. A group of patients repeatedly treated with Phenoterol showed increased cAMP values, particularly evident when compared with those obtained throughout the day. It is notable that this increase does not continue with treatment, but levels off and even shows some tendency to diminish. After the final dose of beta mimetic there is an abrupt fall of cAMP to initial (pre-treatment) values. It is suggested that the increase in nucleotide values is not maintained after repeated doses of beta-stimulants because asthmatics show a diminished response as a result of exhaustion or \"tolerance\" to the response. It is probable that, as in the case of some hormones, the receptors in the effector organs are exhausted."}
{"id": "PMID:223432", "title": "Sexual precocity with hypothalamic hypopituitarism.", "content": "Two girls, one with septo-optic dysplasia and the other with posttraumatic brain damage, had the unusual combination of human growth hormone, thyrotropin, adrenocorticotrophic hormone, and vasopressin deficiencies that were associated with sexual precocity in one patient and early sexual maturation in the second patient, and of adult follicle-stimulating hormone and luteinizing hormone concentrations. At autopsy, the first patient had optic nerve aplasia, a normal pituitary gland, and some disorganization of myelinated fibers in the hypothalamus. The second patient had a normal thyrotropin and prolactin response to thyrotropin-releasing hormone, plus hyperphagia, deranged thirst mechanism, and temperature instability. These findings suggest that the lesion may be a defective hypothalamic regulation of pituitary hormone secretion. Congenital or traumatic hypothalamic-pituitary lesions may not affect all releasing factors or trophic hormones in a similar fashion.", "contents": "Sexual precocity with hypothalamic hypopituitarism. Two girls, one with septo-optic dysplasia and the other with posttraumatic brain damage, had the unusual combination of human growth hormone, thyrotropin, adrenocorticotrophic hormone, and vasopressin deficiencies that were associated with sexual precocity in one patient and early sexual maturation in the second patient, and of adult follicle-stimulating hormone and luteinizing hormone concentrations. At autopsy, the first patient had optic nerve aplasia, a normal pituitary gland, and some disorganization of myelinated fibers in the hypothalamus. The second patient had a normal thyrotropin and prolactin response to thyrotropin-releasing hormone, plus hyperphagia, deranged thirst mechanism, and temperature instability. These findings suggest that the lesion may be a defective hypothalamic regulation of pituitary hormone secretion. Congenital or traumatic hypothalamic-pituitary lesions may not affect all releasing factors or trophic hormones in a similar fashion."}
{"id": "PMID:223433", "title": "Coxsackievirus B epidemic at a boys' camp.", "content": "An epidemic of coxsackievirus B2 infections occured at a boys summer camp. The resulting illness was characterized by malaise, headache, muscle pain, and high fever that persisted for four to six days. The boy in the index case arrived at the camp the first day of the season. The attack rate was 89% among campers and 47% among counselors. The spread of infections appeared to be on a person-to-person basis and in a disorderly fashion. Unusual features of the epidemic included the high attack rate, restriction of infection to the camp residents, and evidence of prolonged pharyngeal viral shedding. Conditions at camps are ripe for similar epidemic and the potential problem is greater than is generally realized.", "contents": "Coxsackievirus B epidemic at a boys' camp. An epidemic of coxsackievirus B2 infections occured at a boys summer camp. The resulting illness was characterized by malaise, headache, muscle pain, and high fever that persisted for four to six days. The boy in the index case arrived at the camp the first day of the season. The attack rate was 89% among campers and 47% among counselors. The spread of infections appeared to be on a person-to-person basis and in a disorderly fashion. Unusual features of the epidemic included the high attack rate, restriction of infection to the camp residents, and evidence of prolonged pharyngeal viral shedding. Conditions at camps are ripe for similar epidemic and the potential problem is greater than is generally realized."}
{"id": "PMID:223434", "title": "Computerized tomography in infantile encephalitis.", "content": "Although computerized tomographic (CT) findings are well recognized in numerous neurologic diseases of children, CT scan abnormalities of encephalitis have only been associated with herpes simplex infection. We describe two infants, one with coxsackievirus B2 meningoencephalitis and one with clinical encephalitis, whose CT scans were similarly abnormal during the acute phase of their illness. In both infants, recovery of both neurologic and developmental deficits was accompanied by resolution of the abnormalities of the initial CT scan. Speculation is offered as to the role of the CT scan in the assistance of the physician who must evaluate both the diagnosis and prognosis of infants who have a clinical picture of encephalitis.", "contents": "Computerized tomography in infantile encephalitis. Although computerized tomographic (CT) findings are well recognized in numerous neurologic diseases of children, CT scan abnormalities of encephalitis have only been associated with herpes simplex infection. We describe two infants, one with coxsackievirus B2 meningoencephalitis and one with clinical encephalitis, whose CT scans were similarly abnormal during the acute phase of their illness. In both infants, recovery of both neurologic and developmental deficits was accompanied by resolution of the abnormalities of the initial CT scan. Speculation is offered as to the role of the CT scan in the assistance of the physician who must evaluate both the diagnosis and prognosis of infants who have a clinical picture of encephalitis."}
{"id": "PMID:223435", "title": "Greig cephalopolysyndactyly syndrome.", "content": "Based on the family presented and five others previously described, it can be concluded that the Grieg cephalopolysyndactyly syndrome is a fully penetrant autosomal dominant disease consisting of four variably expressed malformations: postaxial polydactyly (type B), preaxial polydactyly, syndactyly, and minor craniofacial abnormalities. This entity can be differentiated from other craniofacial-digital syndromes because of the absence of mental retardation, craniosynostosis, and brachydactyly.", "contents": "Greig cephalopolysyndactyly syndrome. Based on the family presented and five others previously described, it can be concluded that the Grieg cephalopolysyndactyly syndrome is a fully penetrant autosomal dominant disease consisting of four variably expressed malformations: postaxial polydactyly (type B), preaxial polydactyly, syndactyly, and minor craniofacial abnormalities. This entity can be differentiated from other craniofacial-digital syndromes because of the absence of mental retardation, craniosynostosis, and brachydactyly."}
{"id": "PMID:223436", "title": "Influenza A virus associated with acute encephalopathy.", "content": "During the period of February 1972 until February 1976, we documented six cases of influenza A-associated acute encephalopathy. The illnesses occurred during periods of influenza A activity in our community. The encephalopathy was invariably preceded by an upper respiratory tract infection, and, thereafter, patients soon became confused, vomited, and showed noticeable restlessness. Patients then followed either of two courses, some becoming comatose within 24 hours and others improving rapidly within three days or less. None of these patients exhibited the hepatic and biochemical abnormalities associated with Reye's syndrome. All patients survived but some had sequelae. The syndrome of influenza-associated acute encephalopathy deserves wider recognition.", "contents": "Influenza A virus associated with acute encephalopathy. During the period of February 1972 until February 1976, we documented six cases of influenza A-associated acute encephalopathy. The illnesses occurred during periods of influenza A activity in our community. The encephalopathy was invariably preceded by an upper respiratory tract infection, and, thereafter, patients soon became confused, vomited, and showed noticeable restlessness. Patients then followed either of two courses, some becoming comatose within 24 hours and others improving rapidly within three days or less. None of these patients exhibited the hepatic and biochemical abnormalities associated with Reye's syndrome. All patients survived but some had sequelae. The syndrome of influenza-associated acute encephalopathy deserves wider recognition."}
{"id": "PMID:223437", "title": "Demonstration of specific antibodies to a coxsackie-like virus in patients of a hepatitis outbreak.", "content": "Lynchburg fecal virus (LFV), originally isolated from the stool of an infectious hepatitis patient, was passaged 15 times in WI-38 cells and partially characterized. Its properties are as follows: RNA virus; 27 nm in diameter, picornavirus-like morphology; inactivated at 56 C for 60 minutes; resistant to treatment with hydrochloric acid (pH 3.0), chloroform (33%), and diethyl ether (20%). Neutralization studies indicated that LFV is antigenically related to coxsackievirus A-24 but not to prototype hepatitis A virus (HAV). The simultaneous occurrence of infections with LFV and with HAV was indicated by the results of enzyme immunoassay (EIA) of the sera of patients of the Lynchburg outbreak. Absence of anti-LFV in patient sera was accompanied by an absence of anti-HAV and, conversely, an increased titer in anti-LFV was accompanied by an increased titer in anti-HAV. Each antibody type was shown to be elicited independently indicating simultaneous infections with LFV and HAV. The contribution, if any, of LFV to disease in the outbreak remains unknown.", "contents": "Demonstration of specific antibodies to a coxsackie-like virus in patients of a hepatitis outbreak. Lynchburg fecal virus (LFV), originally isolated from the stool of an infectious hepatitis patient, was passaged 15 times in WI-38 cells and partially characterized. Its properties are as follows: RNA virus; 27 nm in diameter, picornavirus-like morphology; inactivated at 56 C for 60 minutes; resistant to treatment with hydrochloric acid (pH 3.0), chloroform (33%), and diethyl ether (20%). Neutralization studies indicated that LFV is antigenically related to coxsackievirus A-24 but not to prototype hepatitis A virus (HAV). The simultaneous occurrence of infections with LFV and with HAV was indicated by the results of enzyme immunoassay (EIA) of the sera of patients of the Lynchburg outbreak. Absence of anti-LFV in patient sera was accompanied by an absence of anti-HAV and, conversely, an increased titer in anti-LFV was accompanied by an increased titer in anti-HAV. Each antibody type was shown to be elicited independently indicating simultaneous infections with LFV and HAV. The contribution, if any, of LFV to disease in the outbreak remains unknown."}
{"id": "PMID:223438", "title": "Association of Herpes simplex virus (HSV) with cervical cancer by lymphocyte reactivity with HSV-1 and HSV-2 antigens.", "content": "Twenty-six women with invasive cervical cancer were examined for lymphocyte responsiveness to phytohemagglutinin (PHA) herpes simplex virus (HSV). Blood specimens were obtained from each patient before radiation therapy and separated into subpopulations by Ficoll-Hypaque centrifugation. Lymphocytes were cultured in RPMI-1640 containing autologous plasma and exposed to PHA, HSV-1, HSV-2, and control antigens. The results compared with those of women having negative Papanicolaou smears and matched to the cancer patients by age, race, and socioeconomic class revealed significant differences in blastogenic response (3H-thymidine) to HSV-2 antigens. Results from groups with known HSV-1 and HSV-2 infections indicated that differences were associated with the cancer patients having a higher frequency of HSV-2 infection. Results generally agreed with the findings of previous studies in which serologic test procedures were used.", "contents": "Association of Herpes simplex virus (HSV) with cervical cancer by lymphocyte reactivity with HSV-1 and HSV-2 antigens. Twenty-six women with invasive cervical cancer were examined for lymphocyte responsiveness to phytohemagglutinin (PHA) herpes simplex virus (HSV). Blood specimens were obtained from each patient before radiation therapy and separated into subpopulations by Ficoll-Hypaque centrifugation. Lymphocytes were cultured in RPMI-1640 containing autologous plasma and exposed to PHA, HSV-1, HSV-2, and control antigens. The results compared with those of women having negative Papanicolaou smears and matched to the cancer patients by age, race, and socioeconomic class revealed significant differences in blastogenic response (3H-thymidine) to HSV-2 antigens. Results from groups with known HSV-1 and HSV-2 infections indicated that differences were associated with the cancer patients having a higher frequency of HSV-2 infection. Results generally agreed with the findings of previous studies in which serologic test procedures were used."}
{"id": "PMID:223439", "title": "Infant blood pressure and heart rate: relation to ethnic group (black or white), nutrition and electrolyte intake.", "content": "Blood pressure (BP) and heart rate were measured during non-rapid-eye-movement sleep in 392 full-term newborns and in 318 of these infants at age six months. Two-day records of food intake were collected at age six months for 150 infants. Black babies did not differ substantially in BP from white babies either at birth or at six months. The earliest BP tracking was from age six to 15 months (systolic (SBP): r = .29, p less than .001; diastolic:r = .45, p less than .001). No relationship was found between BP at six months and breast- or bottle-feeding, infant weight or weight change, or nutrient intake. The relationship between parental BP, on the one hand, and infant electrolyte intake and BP on the other, suggested that electrolyte intake was related to BP in the six-month-old infant, and that the relationship was different in white babies than in black babies. Among 56 white infants whose mother's mean BP was above the median for this population, infant sodium intake correlated with infant SBP (r = .31, p less than .009). Among 32 black infants, regardless of parents' BP, sodium intake was negatively correlated with SBP (r = -.36, p less than .021).", "contents": "Infant blood pressure and heart rate: relation to ethnic group (black or white), nutrition and electrolyte intake. Blood pressure (BP) and heart rate were measured during non-rapid-eye-movement sleep in 392 full-term newborns and in 318 of these infants at age six months. Two-day records of food intake were collected at age six months for 150 infants. Black babies did not differ substantially in BP from white babies either at birth or at six months. The earliest BP tracking was from age six to 15 months (systolic (SBP): r = .29, p less than .001; diastolic:r = .45, p less than .001). No relationship was found between BP at six months and breast- or bottle-feeding, infant weight or weight change, or nutrient intake. The relationship between parental BP, on the one hand, and infant electrolyte intake and BP on the other, suggested that electrolyte intake was related to BP in the six-month-old infant, and that the relationship was different in white babies than in black babies. Among 56 white infants whose mother's mean BP was above the median for this population, infant sodium intake correlated with infant SBP (r = .31, p less than .009). Among 32 black infants, regardless of parents' BP, sodium intake was negatively correlated with SBP (r = -.36, p less than .021)."}
{"id": "PMID:223441", "title": "Tumorous phosphaturic osteomalacia. Report of a case associated with multiple hemangiomas of bone.", "content": "A case of osteomalacia associated with hypophosphatemia, decreased tubular reabsorption of phosphorus, hyperphosphaturia and renal glycosuria with associated bone pain and myopathy is presented. The patient was found to have multiple osteolytic lesions of bone which, on biopsy, proved to be sclerosing hemangiomas of bone. Treatment with oral phosphate and vitamin D effected a diminution in his symptoms of bone pain and muscular weakness. The literature on hypophosphatemic phosphaturic osteomalacia associated with mesenchymal tumors is reviewed. It has been suggested that certain mesenchymal tumors elaborate a yet to be identified humoral substance which decreased synthesis of 1 alpha, 25-dihydroxycholecalciferol causing decreased tubular reabsorption of phosphorus, hyperphosphaturia, hypophosphatemic osteomalacia and hypophosphatemic myopathy.", "contents": "Tumorous phosphaturic osteomalacia. Report of a case associated with multiple hemangiomas of bone. A case of osteomalacia associated with hypophosphatemia, decreased tubular reabsorption of phosphorus, hyperphosphaturia and renal glycosuria with associated bone pain and myopathy is presented. The patient was found to have multiple osteolytic lesions of bone which, on biopsy, proved to be sclerosing hemangiomas of bone. Treatment with oral phosphate and vitamin D effected a diminution in his symptoms of bone pain and muscular weakness. The literature on hypophosphatemic phosphaturic osteomalacia associated with mesenchymal tumors is reviewed. It has been suggested that certain mesenchymal tumors elaborate a yet to be identified humoral substance which decreased synthesis of 1 alpha, 25-dihydroxycholecalciferol causing decreased tubular reabsorption of phosphorus, hyperphosphaturia, hypophosphatemic osteomalacia and hypophosphatemic myopathy."}
{"id": "PMID:223442", "title": "Silicosis due to intentional inhalation of abrasive scouring powder. Case report with long-term survival and vasculitic sequelae.", "content": "Silicosis due to inhalation of abrasive scouring powder is now an unusual event. We report a nonindustrial case of acute silicosis due to intentional inhalation of commercial, silica-containing scouring powder. This case is unique in that the patient had a 20 year survival (after onset of symptoms) with typical roentgenographic and histopathologic changes of silicosis, and evidence of immune complex disease in extrapulmonary tissues.", "contents": "Silicosis due to intentional inhalation of abrasive scouring powder. Case report with long-term survival and vasculitic sequelae. Silicosis due to inhalation of abrasive scouring powder is now an unusual event. We report a nonindustrial case of acute silicosis due to intentional inhalation of commercial, silica-containing scouring powder. This case is unique in that the patient had a 20 year survival (after onset of symptoms) with typical roentgenographic and histopathologic changes of silicosis, and evidence of immune complex disease in extrapulmonary tissues."}
{"id": "PMID:223443", "title": "Increased platelet aggregation and decreased high-density lipoprotein cholesterol in women on oral contraceptives.", "content": "In vivo platelet function, serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL), and serum triglycerides (TG) were determined in 26 women starting oral contraceptives (OCA). Studies were run prior to, and after one and two months of therapy. Platelet aggregation time decreased by 50 percent or more in eight of the 26 women from a pre-experimental mean value of 387 +/- 136 seconds. TC did not vary but after the women were on medication for two months, HDL decreased from 56 +/- 14.4 mg/dl to 52 +/- 12.3 mg/dl (p less than 0.05). There was a progressive increase in TG under treatment, 74 +/- 23.3 mg/dl on the pre-experimental measurement to 93 +/- 31.0 mg/dl after two months of therapy (p less than 0.005). Women planning to use OCA might best be advised to have aggregation and serum lipid studies done before and early in usage.", "contents": "Increased platelet aggregation and decreased high-density lipoprotein cholesterol in women on oral contraceptives. In vivo platelet function, serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL), and serum triglycerides (TG) were determined in 26 women starting oral contraceptives (OCA). Studies were run prior to, and after one and two months of therapy. Platelet aggregation time decreased by 50 percent or more in eight of the 26 women from a pre-experimental mean value of 387 +/- 136 seconds. TC did not vary but after the women were on medication for two months, HDL decreased from 56 +/- 14.4 mg/dl to 52 +/- 12.3 mg/dl (p less than 0.05). There was a progressive increase in TG under treatment, 74 +/- 23.3 mg/dl on the pre-experimental measurement to 93 +/- 31.0 mg/dl after two months of therapy (p less than 0.005). Women planning to use OCA might best be advised to have aggregation and serum lipid studies done before and early in usage."}
{"id": "PMID:223445", "title": "Bilateral Paget's disease of the nipple: case report.", "content": "Paget's disease of the breast accounts for 1% to 4.1% of all cancers; however, bilateral Paget's disease is extremely rare. A case of bilateral Paget's disease is presented and treatment is described.", "contents": "Bilateral Paget's disease of the nipple: case report. Paget's disease of the breast accounts for 1% to 4.1% of all cancers; however, bilateral Paget's disease is extremely rare. A case of bilateral Paget's disease is presented and treatment is described."}
{"id": "PMID:223446", "title": "Study of secretory component in patients with metastatic breast cancer.", "content": "A radioimmunoassay was developed for secretory component, a glandular epithelial cell product secreted as an accessory protein with dimeric immunoglobulins A and M. Forty-four normal women between the ages of 40 and 70 had plasma concentrations of secretory component of 7.195 microgram/ml +/- 3.590 (+/-2 SD). Of the patients with metastic breast cancer of epithelial origin, 34 (91.9%) had plasma concentrations greater than 8.990 microgram/ml; 29 (78.1%) had plasma concentrations greater than 10.785 microgram/ml; 10 (27%) had concentrations greater than 15.000 microgram/ml; and 3 (8.1%) had concentrations greater than 22.710 microgram/ml. Serial plasma concentrations (averaging 3.48 per patient) of 35 (94.6%) of these patients reflected the clinical course of the disease. All patients had some combination of surgery, radiation therapy, and chemotherapy. No direct correlation was noted between the type of therapy and concentration of secretory component. However, plasma secretory component served as a marker in the systemic circulation of a change in the status of the metastatic breast cancer. The impact of this research may lie in its incorporation into clinical management.", "contents": "Study of secretory component in patients with metastatic breast cancer. A radioimmunoassay was developed for secretory component, a glandular epithelial cell product secreted as an accessory protein with dimeric immunoglobulins A and M. Forty-four normal women between the ages of 40 and 70 had plasma concentrations of secretory component of 7.195 microgram/ml +/- 3.590 (+/-2 SD). Of the patients with metastic breast cancer of epithelial origin, 34 (91.9%) had plasma concentrations greater than 8.990 microgram/ml; 29 (78.1%) had plasma concentrations greater than 10.785 microgram/ml; 10 (27%) had concentrations greater than 15.000 microgram/ml; and 3 (8.1%) had concentrations greater than 22.710 microgram/ml. Serial plasma concentrations (averaging 3.48 per patient) of 35 (94.6%) of these patients reflected the clinical course of the disease. All patients had some combination of surgery, radiation therapy, and chemotherapy. No direct correlation was noted between the type of therapy and concentration of secretory component. However, plasma secretory component served as a marker in the systemic circulation of a change in the status of the metastatic breast cancer. The impact of this research may lie in its incorporation into clinical management."}
{"id": "PMID:223447", "title": "Comparative pathology of silicate pneumoconiosis.", "content": "A simple pneumoconiosis with lamellar birefringent crystals was observed in animals dying in the San Diego Zoo. We studied 100 autopsies from 11 mammalian and eight avian species. In mammals, mild pulmonary lesions comprised crystal-laden macrophages in alveoli and lymphatics. Interstitial fibrosis was present in 20% of cases. There were no nodules. In birds, dust retention produced large granulomas around tertiary bronchi without fibrosis. Mineralogic analysis using scanning and transmission electron microscopy showed most of the crystals to be silicates. Ninety percent were complex silicates, with aluminum-potassium silicates comprising 70% of the analyzed particles. Electron and x-ray diffraction showed the silicates to be muscovite mica and its hydrothermal degradation product, ie, illite clay. This mica was also present on filtration membranes of atmospheric air samples obtained from the San Diego Zoo. The amount of dust retention was related to the animal's age, anatomic or ecologic variances, and length of stay in the San Diego Zoo. Its semidesert atmosphere is rich in silicates, which are inhaled and deposited in the lungs. Similar mica-induced lesions are found in humans living in this region or the Southwest of the USA. This simple pneumoconiosis is likely to be widespread in human populations living in desert or semidesert climates.", "contents": "Comparative pathology of silicate pneumoconiosis. A simple pneumoconiosis with lamellar birefringent crystals was observed in animals dying in the San Diego Zoo. We studied 100 autopsies from 11 mammalian and eight avian species. In mammals, mild pulmonary lesions comprised crystal-laden macrophages in alveoli and lymphatics. Interstitial fibrosis was present in 20% of cases. There were no nodules. In birds, dust retention produced large granulomas around tertiary bronchi without fibrosis. Mineralogic analysis using scanning and transmission electron microscopy showed most of the crystals to be silicates. Ninety percent were complex silicates, with aluminum-potassium silicates comprising 70% of the analyzed particles. Electron and x-ray diffraction showed the silicates to be muscovite mica and its hydrothermal degradation product, ie, illite clay. This mica was also present on filtration membranes of atmospheric air samples obtained from the San Diego Zoo. The amount of dust retention was related to the animal's age, anatomic or ecologic variances, and length of stay in the San Diego Zoo. Its semidesert atmosphere is rich in silicates, which are inhaled and deposited in the lungs. Similar mica-induced lesions are found in humans living in this region or the Southwest of the USA. This simple pneumoconiosis is likely to be widespread in human populations living in desert or semidesert climates."}
{"id": "PMID:223448", "title": "Endocrine regulation of thymic biosynthetic polyamine decarboxylases in adult rat.", "content": "The activities of ornithine and S-adenosyl-L-methionine decarboxylase were assayed in the thymuses of adult rats killed at 7-day intervals up to 6 wk after either pinealectomy or sham pinealectomy. The absence of the pineal gland markedly influenced the ornithine decarboxylase activity in the thymus, in which the level of the enzyme was decreased permanently by the 4th wk after the operation (P less than 0.05). The time course of the changes in S-adenosyl-L-methionine decarboxylase activity in the thymus during the entire period investigated was also significantly (P less than 0.05) modified by pinealectomy but did not show any stable trend. Adrenalectomy significantly raised (P less than 0.001) for ornithine decarboxylase; P less than 0.01 for S-adenosyl-L-methionine decarboxylase) the basal levels of the thymic biosynthetic polyamine decarboxylases. A pharmacological dose of corticosterone or cortisol produced a rapid and significant decrease in ornithine and S-adenosyl-L-methionine decarboxylase activities (P less than 0.02) in the thymus, whereas the injection of either D-aldosterone or ACTH was ineffective. Therefore, the thymic biosynthetic polyamine decarboxylases that in this organ are known to be located only in the lymphocytes appear to be regulated in opposing ways by the pineal gland and by the adrenal cortex.", "contents": "Endocrine regulation of thymic biosynthetic polyamine decarboxylases in adult rat. The activities of ornithine and S-adenosyl-L-methionine decarboxylase were assayed in the thymuses of adult rats killed at 7-day intervals up to 6 wk after either pinealectomy or sham pinealectomy. The absence of the pineal gland markedly influenced the ornithine decarboxylase activity in the thymus, in which the level of the enzyme was decreased permanently by the 4th wk after the operation (P less than 0.05). The time course of the changes in S-adenosyl-L-methionine decarboxylase activity in the thymus during the entire period investigated was also significantly (P less than 0.05) modified by pinealectomy but did not show any stable trend. Adrenalectomy significantly raised (P less than 0.001) for ornithine decarboxylase; P less than 0.01 for S-adenosyl-L-methionine decarboxylase) the basal levels of the thymic biosynthetic polyamine decarboxylases. A pharmacological dose of corticosterone or cortisol produced a rapid and significant decrease in ornithine and S-adenosyl-L-methionine decarboxylase activities (P less than 0.02) in the thymus, whereas the injection of either D-aldosterone or ACTH was ineffective. Therefore, the thymic biosynthetic polyamine decarboxylases that in this organ are known to be located only in the lymphocytes appear to be regulated in opposing ways by the pineal gland and by the adrenal cortex."}
{"id": "PMID:223450", "title": "Renal metabolism of N6,O2'-dibutyryl adenosine 3',5'-monophosphate.", "content": "Metabolism of dibutyryl cyclic AMP was studied by including the 3H- or C-labeled nucleotide (0.1 mM, 5 mumol) in the recirculating perfusate of the isolated rat kidney. Kidneys were perfused with nucleotide for 60 min. Dibutyryl cyclic AMP was almost completely cleared from the perfusate, about one-quarter as urinary excretion principally by probenecid-sensitive secretion and about one-half as metabolism beyond 3'-phosphate bond cleavage. The principal metabolite, N6-monobutyryl adenosine, accounted for one-third of added dibutyryl cyclic AMP. The remaining metabolites were ATP, ADP AMP, and N6-monobutyryl AMP. Dibutyryl cyclic AMP (0.1 or 1.0 mM) elevated renal ATP but did not alter uricogenesis. Both dibutyryl cyclic AMP and cyclic AMP at 0.2 mM produced similar activation and subcellular redistribution of renal protein kinase. N6-monobutyryl adenosine, unlike adenosine, had no effect on the renal activity of adenylate cyclase, low Km cyclic AMP phosphodiesterase, and protein kinase. Dibutyryl cyclic AMP is like exogenous cyclic AMP in that it penetrates the rat kidney, activates protein kinase, and is metabolized to ATP (R. Coulson, J. Biol. Chem. 251: 4958-4967, 1976), but is unlike cyclic AMP in its extent of secretion and metabolism to ATP and urate and in its formation of the unique metabolites N6-monobutyryl AMP and N6-monobutyryl adenosine.", "contents": "Renal metabolism of N6,O2'-dibutyryl adenosine 3',5'-monophosphate. Metabolism of dibutyryl cyclic AMP was studied by including the 3H- or C-labeled nucleotide (0.1 mM, 5 mumol) in the recirculating perfusate of the isolated rat kidney. Kidneys were perfused with nucleotide for 60 min. Dibutyryl cyclic AMP was almost completely cleared from the perfusate, about one-quarter as urinary excretion principally by probenecid-sensitive secretion and about one-half as metabolism beyond 3'-phosphate bond cleavage. The principal metabolite, N6-monobutyryl adenosine, accounted for one-third of added dibutyryl cyclic AMP. The remaining metabolites were ATP, ADP AMP, and N6-monobutyryl AMP. Dibutyryl cyclic AMP (0.1 or 1.0 mM) elevated renal ATP but did not alter uricogenesis. Both dibutyryl cyclic AMP and cyclic AMP at 0.2 mM produced similar activation and subcellular redistribution of renal protein kinase. N6-monobutyryl adenosine, unlike adenosine, had no effect on the renal activity of adenylate cyclase, low Km cyclic AMP phosphodiesterase, and protein kinase. Dibutyryl cyclic AMP is like exogenous cyclic AMP in that it penetrates the rat kidney, activates protein kinase, and is metabolized to ATP (R. Coulson, J. Biol. Chem. 251: 4958-4967, 1976), but is unlike cyclic AMP in its extent of secretion and metabolism to ATP and urate and in its formation of the unique metabolites N6-monobutyryl AMP and N6-monobutyryl adenosine."}
{"id": "PMID:223451", "title": "Influence of hypothalamic and ambient temperatures on sleep in kangaroo rats.", "content": "Unanesthetized, unrestrained kangaroo rats (Dipodomys) were studied to examine the changes in the frequency and duration of sleep states caused by long-term manipulations of hypothalamic temperature (Thy) at a thermoneutral (30 degrees C) and a low (20 degrees C) ambient temperature (Ta). A cold stimulus present in either the hypothalamus or the skin decreased both the total sleep time (TST) and the ratio of paradoxical sleep (PS) to TST. At a low Ta, TST, but not the PS-to-TST ratio, was increased by raising Thy, indicating that a cold peripheral stimulus could differentially inhibit PS. At a thermoneutral Ta, cooling Thy decreased both TST and the PS/TST. Changes in the amount of PS were due largely to changes in the frequency, but not the duration, of individual episodes of PS, suggesting that the transition to PS is partially dependent on the thermoregulatory conditions existing during slow-wave sleep (SWS). These results are consistent with the recent findings that the thermoregulatory system is functional during SWS but is inhibited or inactivated during PS.", "contents": "Influence of hypothalamic and ambient temperatures on sleep in kangaroo rats. Unanesthetized, unrestrained kangaroo rats (Dipodomys) were studied to examine the changes in the frequency and duration of sleep states caused by long-term manipulations of hypothalamic temperature (Thy) at a thermoneutral (30 degrees C) and a low (20 degrees C) ambient temperature (Ta). A cold stimulus present in either the hypothalamus or the skin decreased both the total sleep time (TST) and the ratio of paradoxical sleep (PS) to TST. At a low Ta, TST, but not the PS-to-TST ratio, was increased by raising Thy, indicating that a cold peripheral stimulus could differentially inhibit PS. At a thermoneutral Ta, cooling Thy decreased both TST and the PS/TST. Changes in the amount of PS were due largely to changes in the frequency, but not the duration, of individual episodes of PS, suggesting that the transition to PS is partially dependent on the thermoregulatory conditions existing during slow-wave sleep (SWS). These results are consistent with the recent findings that the thermoregulatory system is functional during SWS but is inhibited or inactivated during PS."}
{"id": "PMID:223453", "title": "Receptor affinity and biological potency of thyroid hormones in thyrotropic cells.", "content": "The nuclear receptor affinity for L-triiodothyronine (L-T3), L-thyroxine (L-T4), L-triiodothyroacetic acid (triac), and D-triiodothyronine (D-T3) was compared to the potency of these thyroid hormone analogues in regulating thyrotropin (TSH) production and the number of membrane receptors for thyrotropin-releasing hormone (TRH) in mouse thyrotropic tumor cells in culture. L-T3 and triac were equally potent and D-T3 was one-sixth to one-fifth as potent in binding to the receptor and in regulating TSH production and TRH receptor number. L-T4 was the least potent analogue in each instance, but its relative receptor-binding affinity, measured after 3 h, was significantly less than its somewhat variable relative biological potency, measured after 48 h. The cells were shown to monodeiodinate L-[125I]T4 to L-[125I]T3 in a time-dependent manner, and the enhanced biological potency of L-T4 was ascribed to its conversion to L-T3. Thyroid hormones appear to regulate TSH production and the number of receptors for TRH in thyrotropic cells in culture through interaction with a nuclear receptor.", "contents": "Receptor affinity and biological potency of thyroid hormones in thyrotropic cells. The nuclear receptor affinity for L-triiodothyronine (L-T3), L-thyroxine (L-T4), L-triiodothyroacetic acid (triac), and D-triiodothyronine (D-T3) was compared to the potency of these thyroid hormone analogues in regulating thyrotropin (TSH) production and the number of membrane receptors for thyrotropin-releasing hormone (TRH) in mouse thyrotropic tumor cells in culture. L-T3 and triac were equally potent and D-T3 was one-sixth to one-fifth as potent in binding to the receptor and in regulating TSH production and TRH receptor number. L-T4 was the least potent analogue in each instance, but its relative receptor-binding affinity, measured after 3 h, was significantly less than its somewhat variable relative biological potency, measured after 48 h. The cells were shown to monodeiodinate L-[125I]T4 to L-[125I]T3 in a time-dependent manner, and the enhanced biological potency of L-T4 was ascribed to its conversion to L-T3. Thyroid hormones appear to regulate TSH production and the number of receptors for TRH in thyrotropic cells in culture through interaction with a nuclear receptor."}
{"id": "PMID:223454", "title": "Synthesis of taurocholate by rat fetal liver in organ culture: effects of cortisol in vitro.", "content": "Taurocholate production by fetal hepatic organ cultures was measured by radioimmunoassay. Taurocholate production was maximal on day 1 of in vitro incubation, but was demonstrable in organ cultures maintained for periods up to 15 days. Explants obtained from fetuses of 18 gestational days of age produced only 82 pmol taurocholate per milligram dry weight of tissue during the first 24 h of incubation. Explants obtained from fetuses 21 gestational days of age produced 1,043 pmol taurocholate per milligram dry weight. The presence of cortisol (2.0 X 10(-6) M) in the incubation medium increased synthesis of taurocholate by rat fetal liver in which total taurocholate rose 50-fold above control after 120 h of incubation. In increasing concentrations from 2.0 X 10(-9) M to 2.0 X 10(-7) M, cortisol produced an incremental rise in taurocholate. However, additional increases in cortisol dose failed to provide further stimulation, and taurocholate production was inhibited by cortisol concentrations of 2.0 X 10(-5) M. The results provide further validation for the technique of fetal hepatic organ culture. They demonstrate that taurocholate synthesis is increasing rapidly during the final stages of gestation and show that cortisol augments taurocholate synthesis in a dose-response pattern.", "contents": "Synthesis of taurocholate by rat fetal liver in organ culture: effects of cortisol in vitro. Taurocholate production by fetal hepatic organ cultures was measured by radioimmunoassay. Taurocholate production was maximal on day 1 of in vitro incubation, but was demonstrable in organ cultures maintained for periods up to 15 days. Explants obtained from fetuses of 18 gestational days of age produced only 82 pmol taurocholate per milligram dry weight of tissue during the first 24 h of incubation. Explants obtained from fetuses 21 gestational days of age produced 1,043 pmol taurocholate per milligram dry weight. The presence of cortisol (2.0 X 10(-6) M) in the incubation medium increased synthesis of taurocholate by rat fetal liver in which total taurocholate rose 50-fold above control after 120 h of incubation. In increasing concentrations from 2.0 X 10(-9) M to 2.0 X 10(-7) M, cortisol produced an incremental rise in taurocholate. However, additional increases in cortisol dose failed to provide further stimulation, and taurocholate production was inhibited by cortisol concentrations of 2.0 X 10(-5) M. The results provide further validation for the technique of fetal hepatic organ culture. They demonstrate that taurocholate synthesis is increasing rapidly during the final stages of gestation and show that cortisol augments taurocholate synthesis in a dose-response pattern."}
{"id": "PMID:223455", "title": "Determination of Na-K-ATPase activity in single segments of the mammalian nephron.", "content": "A micromethod for the determination of Na-K-ATPase in discrete segments of nephrons from rabbit, rat, and mouse kidneys is described. To facilitate tubule microdissection, the kidneys were perfused with collagenase after it had been verified that collagenase had no effect on ATPase activity. Individual tubule segments were dissected under stereomicroscopic observation, exposed to a hypotonic environment followed by rapid freezing, and incubated in 1 microliter assay medium. Enzyme activity was determined by direct measurement of labeled inorganic phosphate release by the hydrolysis of [gamma-32P]ATP and was expressed as a function of tubule length. This method is technically simple enough to permit simultaneous measurement of the enzyme in large numbers of tubules and sufficiently sensitive to determine its activity in each region of the nephron. Correlation of Na-K-ATPase activity in single tubules with functional measurements obtained in the corresponding segment of the nephron with the perfused tubule or micropuncture techniques should help define the role of this enzyme in tubular ion transport.", "contents": "Determination of Na-K-ATPase activity in single segments of the mammalian nephron. A micromethod for the determination of Na-K-ATPase in discrete segments of nephrons from rabbit, rat, and mouse kidneys is described. To facilitate tubule microdissection, the kidneys were perfused with collagenase after it had been verified that collagenase had no effect on ATPase activity. Individual tubule segments were dissected under stereomicroscopic observation, exposed to a hypotonic environment followed by rapid freezing, and incubated in 1 microliter assay medium. Enzyme activity was determined by direct measurement of labeled inorganic phosphate release by the hydrolysis of [gamma-32P]ATP and was expressed as a function of tubule length. This method is technically simple enough to permit simultaneous measurement of the enzyme in large numbers of tubules and sufficiently sensitive to determine its activity in each region of the nephron. Correlation of Na-K-ATPase activity in single tubules with functional measurements obtained in the corresponding segment of the nephron with the perfused tubule or micropuncture techniques should help define the role of this enzyme in tubular ion transport."}
{"id": "PMID:223456", "title": "Na-K-ATPase activity along the rabbit, rat, and mouse nephron.", "content": "Na-K-ATPase activity along the rabbit, rat, and mouse nephron was determined with a micromethod that measures directly labeled phosphate released by the hydrolysis of [gamma-32P]ATP. Na-K-ATPase activity was highest in the rat, intermediate in the mouse, and lowest in the rabbit nephron. With the exception of rabbit cortical thick ascending limb, the enzyme profile was similar in the three species: Na-K-ATPase activity per millimeter tubule length was highest in the distal convoluted tubule and thick ascending limb of Henle's loop, intermediate in the proximal convoluted tubule, and lowest in the pars recta and collecting tubule. The enzyme was present in the thin limbs of Henle's loop, but its activity was very low and measurements were close to the sensitivity limit of the method. Both the absolute activity and the fraction of the total enzyme represented by Na-K-ATPase were severalfold higher than in kidney homogenates. Finally, the Na-K-ATPase activity measured in certain segments of the rat and rabbit nephron in this study seems sufficient to account in theory for the active component of the net sodium transport found in the corresponding region of the nephron with either in vivo or in vitro single tubule microperfusion techniques.", "contents": "Na-K-ATPase activity along the rabbit, rat, and mouse nephron. Na-K-ATPase activity along the rabbit, rat, and mouse nephron was determined with a micromethod that measures directly labeled phosphate released by the hydrolysis of [gamma-32P]ATP. Na-K-ATPase activity was highest in the rat, intermediate in the mouse, and lowest in the rabbit nephron. With the exception of rabbit cortical thick ascending limb, the enzyme profile was similar in the three species: Na-K-ATPase activity per millimeter tubule length was highest in the distal convoluted tubule and thick ascending limb of Henle's loop, intermediate in the proximal convoluted tubule, and lowest in the pars recta and collecting tubule. The enzyme was present in the thin limbs of Henle's loop, but its activity was very low and measurements were close to the sensitivity limit of the method. Both the absolute activity and the fraction of the total enzyme represented by Na-K-ATPase were severalfold higher than in kidney homogenates. Finally, the Na-K-ATPase activity measured in certain segments of the rat and rabbit nephron in this study seems sufficient to account in theory for the active component of the net sodium transport found in the corresponding region of the nephron with either in vivo or in vitro single tubule microperfusion techniques."}
{"id": "PMID:223457", "title": "Hormonal regulation of active chloride transport in the dogfish rectal gland.", "content": "Active transport of chloride is modulated by cyclic AMP in the rectal gland of Squalus acanthias. Vasoactive intestinal peptide (VIP) specifically activates the production of cyclic AMP by the gland and stimulates the secretion of chloride. Somatostatin inhibits VIP-induced secretion but has no effect alone. Both these peptides are present in the dogfish shark and may play an important role in electrolyte homeostasis.", "contents": "Hormonal regulation of active chloride transport in the dogfish rectal gland. Active transport of chloride is modulated by cyclic AMP in the rectal gland of Squalus acanthias. Vasoactive intestinal peptide (VIP) specifically activates the production of cyclic AMP by the gland and stimulates the secretion of chloride. Somatostatin inhibits VIP-induced secretion but has no effect alone. Both these peptides are present in the dogfish shark and may play an important role in electrolyte homeostasis."}
{"id": "PMID:223458", "title": "Electroconvulsive therapy for iatrogenic hypothalamic-hypopituitarism (CRF-ACTH type).", "content": "A 41-year-old man with hypothalamic hypopituitarism (CRF-ACTH type) that persisted for 2 years after discontinuation of exogenous dexamethasone was treated with bilateral ECT for severe chronic depression. The depression improved only evanescently after 17 ECT sessions but the hypothalamic-pituitary suppression cleared completely and permanently, based on responses to four metyrapone stress tests in a 2-year follow-up period. ECT may be an effective treatment for persistent hypothalamic-pituitary suppression, even in the absence of a psychiatric disorder.", "contents": "Electroconvulsive therapy for iatrogenic hypothalamic-hypopituitarism (CRF-ACTH type). A 41-year-old man with hypothalamic hypopituitarism (CRF-ACTH type) that persisted for 2 years after discontinuation of exogenous dexamethasone was treated with bilateral ECT for severe chronic depression. The depression improved only evanescently after 17 ECT sessions but the hypothalamic-pituitary suppression cleared completely and permanently, based on responses to four metyrapone stress tests in a 2-year follow-up period. ECT may be an effective treatment for persistent hypothalamic-pituitary suppression, even in the absence of a psychiatric disorder."}
{"id": "PMID:223459", "title": "Experimental amebiasis. IV. Amebal viruses and the virulence of Entamoeba histolytica.", "content": "We have attempted to determine whether amebal viruses are capable of viral conversion of the virulence of Entamoeba histolytical. Amebae of little or no virulence for the newborn hamster liver were infected with viruses obtained from four amebal strains of different virulence. Cultures of surviving amebae were increased in virulence by viruses from amebae of high, moderate, or low virulence, but decreased in virulence by the virus of the second most pathogenic amebal strain. Sequential infection with two viruses did not produce consistent cumulative effects on virulence. The changes in virulence noted are considered to be the unpredictable result of either selection pressures exerted by the lytic virus infection or possibly viral alterations of the amebae.", "contents": "Experimental amebiasis. IV. Amebal viruses and the virulence of Entamoeba histolytica. We have attempted to determine whether amebal viruses are capable of viral conversion of the virulence of Entamoeba histolytical. Amebae of little or no virulence for the newborn hamster liver were infected with viruses obtained from four amebal strains of different virulence. Cultures of surviving amebae were increased in virulence by viruses from amebae of high, moderate, or low virulence, but decreased in virulence by the virus of the second most pathogenic amebal strain. Sequential infection with two viruses did not produce consistent cumulative effects on virulence. The changes in virulence noted are considered to be the unpredictable result of either selection pressures exerted by the lytic virus infection or possibly viral alterations of the amebae."}
{"id": "PMID:223460", "title": "Immunoperoxidase staining for detection of Colorado tick fever virus, and a study of congenital infection in the mouse.", "content": "Indirect immunoperoxidase (IP) staining was evaluated for sensitivity and specificity in detecting Colorado tick fever (CTF) virus antigen in infected cell cultures and infected mouse tissues, and then was applied to a study of congenital CTF infection in mice. The sensitivity of IP staining was comparable to that of immunofluorescence staining in detecting CTF antigen in infected cell cultures. Endogenous peroxidase activity of mouse tissues caused nonspecific reactivity in the IP system, but this could be abolished by treatment with sodium azide and hydrogen peroxide without destroying CTF antigen. Offspring of mice infected with CTF virus during the 2nd week of pregnancy showed a highly significant increase in the incidence of stillbirths and neonatal deaths as compared with offspring of uninfected controls. CTF antigen or virus was demonstrable in only a low proportion (7%) of embryos, ill newborns or stillborns examined, but a high proportion of mice examined at a time when maternal antibody would be lost (6 and 12 weeks) showed CTF antibody, indicating a higher incidence of infection. IP staining showed potential for use in studies of viral pathogenesis in the mouse model.", "contents": "Immunoperoxidase staining for detection of Colorado tick fever virus, and a study of congenital infection in the mouse. Indirect immunoperoxidase (IP) staining was evaluated for sensitivity and specificity in detecting Colorado tick fever (CTF) virus antigen in infected cell cultures and infected mouse tissues, and then was applied to a study of congenital CTF infection in mice. The sensitivity of IP staining was comparable to that of immunofluorescence staining in detecting CTF antigen in infected cell cultures. Endogenous peroxidase activity of mouse tissues caused nonspecific reactivity in the IP system, but this could be abolished by treatment with sodium azide and hydrogen peroxide without destroying CTF antigen. Offspring of mice infected with CTF virus during the 2nd week of pregnancy showed a highly significant increase in the incidence of stillbirths and neonatal deaths as compared with offspring of uninfected controls. CTF antigen or virus was demonstrable in only a low proportion (7%) of embryos, ill newborns or stillborns examined, but a high proportion of mice examined at a time when maternal antibody would be lost (6 and 12 weeks) showed CTF antibody, indicating a higher incidence of infection. IP staining showed potential for use in studies of viral pathogenesis in the mouse model."}
{"id": "PMID:223461", "title": "Dimethyl sulfoxide enhancement of phlebotomus fever virus plaque formation.", "content": "Dimethyl sulfoxide (DMSO)incorporated into an agar overlay containing DEAE-dextran enhanced plaque formation in Vero cells by Naples sandfly fever virus passaged in mouse brain or Vero cell cultures. No plaques were visible when DMSO was used without the DEAE-dextran, some plaques were rarely visible (less than 0.5mm) when DEAE-dextran was used without the DMSO, and up to 10-fold more plaques were clearly visible (0.5-1.5 mm) when both chemicals were used. The combined enhancing effect of DMSO and DEAE-dextran was also observed with mouse brain passaged, but not Vero passaged Sicilian sandfly fever virus. Other Phlebotomus group viruses produced a bit plaques (3-5 mm) and did not require DMSO for plaque formation, although an increase in plaque clarity was obtained with DMSO for some of them. Plaque reduction neutralization tests were assayed successfully under agar containing DMSO. The alphavirus Sindbis produced slightly larger plaques under agar containing DMSO, but there was no effect on clarity or size of plaques produced by the flavivirus dengue-2.", "contents": "Dimethyl sulfoxide enhancement of phlebotomus fever virus plaque formation. Dimethyl sulfoxide (DMSO)incorporated into an agar overlay containing DEAE-dextran enhanced plaque formation in Vero cells by Naples sandfly fever virus passaged in mouse brain or Vero cell cultures. No plaques were visible when DMSO was used without the DEAE-dextran, some plaques were rarely visible (less than 0.5mm) when DEAE-dextran was used without the DMSO, and up to 10-fold more plaques were clearly visible (0.5-1.5 mm) when both chemicals were used. The combined enhancing effect of DMSO and DEAE-dextran was also observed with mouse brain passaged, but not Vero passaged Sicilian sandfly fever virus. Other Phlebotomus group viruses produced a bit plaques (3-5 mm) and did not require DMSO for plaque formation, although an increase in plaque clarity was obtained with DMSO for some of them. Plaque reduction neutralization tests were assayed successfully under agar containing DMSO. The alphavirus Sindbis produced slightly larger plaques under agar containing DMSO, but there was no effect on clarity or size of plaques produced by the flavivirus dengue-2."}
{"id": "PMID:223462", "title": "Discriminant analysis: a method of identifying foci of vector-borne diseases.", "content": "Identification of foci of vector-borne diseases does not require knowledge of exact abundances of vectors and pathogens; rather, a focus is defined by the presence, or some minimal level of abundance, of a vector and pathogen. Stepwise discriminant analysis (DA) was applied to data on free-ranging adult wood ticks (the vector) and to data on isolations of Colorado tick fever virus from small mammals. Trap stations were grouped on the basis of relative abundance of wood ticks for one set of analyses and on the presence or absence of virus for another set of analyses. Additional data consisted of easily measured environmental variables. It is concluded that DA provides a useful tool for analysis of ecosystem structure and an effective means of identifying foci of infection.", "contents": "Discriminant analysis: a method of identifying foci of vector-borne diseases. Identification of foci of vector-borne diseases does not require knowledge of exact abundances of vectors and pathogens; rather, a focus is defined by the presence, or some minimal level of abundance, of a vector and pathogen. Stepwise discriminant analysis (DA) was applied to data on free-ranging adult wood ticks (the vector) and to data on isolations of Colorado tick fever virus from small mammals. Trap stations were grouped on the basis of relative abundance of wood ticks for one set of analyses and on the presence or absence of virus for another set of analyses. Additional data consisted of easily measured environmental variables. It is concluded that DA provides a useful tool for analysis of ecosystem structure and an effective means of identifying foci of infection."}
{"id": "PMID:223473", "title": "The development of functional heterogeneity in the liver parenchyma of the golden hamster.", "content": "Prenatal and postnatal stages of the development of golden hamsters were studied histochemically and biochemically. It was shown that, beginning with the 12th gestational day, the fetal liver starts to store glycogen, and that this process reaches its maximum a birth. Glycogen phosphorylase and glucose-6-phosphatase (G6Pase)-activity increased drastically in the last two days before birth, glycogen phosphorylase preceding G6Pase. As a histochemical characteristic, an even distribution of glycogen, glycogen phosphorylase and G6Pase activity is found in the liver parenchyma at birth. During the first two postnatal weeks typical heterogeneous patterns of distribution developed: glycogen depletion could be demonstrated predominantly in zone 1 of the liver acinus, this being at the same time the area of highest glycogen phosphorylase and G6Pase-activity. The periportal zone 1 thus became characterized as the primary site of glycogenolysis (glycogen phosphorylase) and gluco(neo)genesis (G6Pase). \"Metabolic Zonation\" is interpreted as the chemomorphological equivalent of the regulatory function of the liver as a glucostat.", "contents": "The development of functional heterogeneity in the liver parenchyma of the golden hamster. Prenatal and postnatal stages of the development of golden hamsters were studied histochemically and biochemically. It was shown that, beginning with the 12th gestational day, the fetal liver starts to store glycogen, and that this process reaches its maximum a birth. Glycogen phosphorylase and glucose-6-phosphatase (G6Pase)-activity increased drastically in the last two days before birth, glycogen phosphorylase preceding G6Pase. As a histochemical characteristic, an even distribution of glycogen, glycogen phosphorylase and G6Pase activity is found in the liver parenchyma at birth. During the first two postnatal weeks typical heterogeneous patterns of distribution developed: glycogen depletion could be demonstrated predominantly in zone 1 of the liver acinus, this being at the same time the area of highest glycogen phosphorylase and G6Pase-activity. The periportal zone 1 thus became characterized as the primary site of glycogenolysis (glycogen phosphorylase) and gluco(neo)genesis (G6Pase). \"Metabolic Zonation\" is interpreted as the chemomorphological equivalent of the regulatory function of the liver as a glucostat."}
{"id": "PMID:223474", "title": "Intramitochondrial rod-like inclusions in human breast tumors.", "content": "Ultrastructural screening of human breast tumor biopsies has revealed, in 43% of the carcinomas, and in 16% of the benign lesions examined. the presence of rod-like inclusions in mitochondria of epithelial cells. The inclusions are cylindrical in cross section, with a diameter of about 50 nm, and show regular striations in longitudinal sections. They are probably derived from cristae. Mitochondria with inclusions are usually enlarged and are found most frequently in epithelial cells of invasive tumors and near zones of tumor necrosis. Similar although not identical inclusions have been observed by other investigators in the liver of women with hydatidiform mole or choriocarcinoma, of pregnant women, and of women taking oral contraceptives. Identical inclusions have been found in mitochondria of HeLa cells treated with anti-HeLa serum. Although no clear-cut correlations were found between the finding of inclusions and parameters such as age of patients, nuclear grade or lymphocytic infiltration of the breast tumors, it is conceivable that the presence of mitochondrial inclusions reflects the effect of hormonal or of immunological factors.", "contents": "Intramitochondrial rod-like inclusions in human breast tumors. Ultrastructural screening of human breast tumor biopsies has revealed, in 43% of the carcinomas, and in 16% of the benign lesions examined. the presence of rod-like inclusions in mitochondria of epithelial cells. The inclusions are cylindrical in cross section, with a diameter of about 50 nm, and show regular striations in longitudinal sections. They are probably derived from cristae. Mitochondria with inclusions are usually enlarged and are found most frequently in epithelial cells of invasive tumors and near zones of tumor necrosis. Similar although not identical inclusions have been observed by other investigators in the liver of women with hydatidiform mole or choriocarcinoma, of pregnant women, and of women taking oral contraceptives. Identical inclusions have been found in mitochondria of HeLa cells treated with anti-HeLa serum. Although no clear-cut correlations were found between the finding of inclusions and parameters such as age of patients, nuclear grade or lymphocytic infiltration of the breast tumors, it is conceivable that the presence of mitochondrial inclusions reflects the effect of hormonal or of immunological factors."}
{"id": "PMID:223475", "title": "Feline plasma cortisol (hydrocortisone) measured by radioimmunoassay.", "content": "Plasma cortisol (hydrocortisone) was measured by radioimmunoassay in 6 normal cats. Blood was collected from the cats by venipuncture at intervals of 3 hours for 3 days. Resting plasma cortisol concentrations averaged 17.0 +/- 2.8 (SD) ng/ml and ranged from nondetectable (less than 3 ng/ml) to 82.8 ng/ml. Of 144 plasma samples, 95% contained less than 40 ng of cortisol/ml. Circadian rhythm of cortisol secretion was not detected, suggesting that adrenal function tests may be started in feline patients at any time of day. Intramuscular injection of 2.2 U of ACTH gel/kg of body weight caused detectable increase in plasma cortisol concentrations at 1 and 2 hours after injection. Maximal response to ACTH in the 6 cats ranged from 41.6 to 178.4 ng/ml. Oral administration of 0.1 mg of dexamethasone/kg suppressed plasma cortisol to nondetectable concentrations for 32 hours in 5 of the 6 cats.", "contents": "Feline plasma cortisol (hydrocortisone) measured by radioimmunoassay. Plasma cortisol (hydrocortisone) was measured by radioimmunoassay in 6 normal cats. Blood was collected from the cats by venipuncture at intervals of 3 hours for 3 days. Resting plasma cortisol concentrations averaged 17.0 +/- 2.8 (SD) ng/ml and ranged from nondetectable (less than 3 ng/ml) to 82.8 ng/ml. Of 144 plasma samples, 95% contained less than 40 ng of cortisol/ml. Circadian rhythm of cortisol secretion was not detected, suggesting that adrenal function tests may be started in feline patients at any time of day. Intramuscular injection of 2.2 U of ACTH gel/kg of body weight caused detectable increase in plasma cortisol concentrations at 1 and 2 hours after injection. Maximal response to ACTH in the 6 cats ranged from 41.6 to 178.4 ng/ml. Oral administration of 0.1 mg of dexamethasone/kg suppressed plasma cortisol to nondetectable concentrations for 32 hours in 5 of the 6 cats."}
{"id": "PMID:223476", "title": "Demonstration of cytotoxic lymphocytes to virus-infected target cells in pigs inoculated with transmissible gastroenteritis virus.", "content": "Lymphocytes, cytotoxic to virus-infected target cells, were induced in pigs orally exposed to transmissible gastroenteritis virus. They were studied and experiments were carried out by using autochthonous testicle cells as target cells to avoid genetic incompatibility of effector lymphocytes and target cells. Cytotoxic lymphocytes were demonstrated in Peyer's patches, mesenteric lymph nodes, spleen, and peripheral blood on postinoculation day (PID) 7. Cytotoxic activity of lymphocytes increased thereafter and reached the maximal amount at PID 21. Lymphocyte cytotoxicity was somewhat greater in lymphocytes of peripheral blood and spleen than in those of Peyer's patches and mesenteric lymph nodes after PID 14. On the contrary, lymphocyte reactivity to the viral antigen measured by lymphocyte proliferative assay was higher in Peyer's patch and mesenteric lymph node cells than in peripheral blood and splenic cells. Lymphocyte cytotoxicity was depressed by treating effector cells with anti-porcine thymocyte serum and complement. However, lymphocyte suspensions treated with anti-porcine thymocyte serum and complement were still cytotoxic to some extent against virus-infected target cells, although T lymphocytes were completely excluded by the treatment. This suggests that cytotoxic mechanism other than the direct action of cytotoxic T lymphocytes may be involved in the cytotoxicity assay systems used in the present studies. In experiments in which allogenic cells (testicle cells of siblings) were used together with autochthonous cells as targets, lymphocyte cytotoxicity was equally expressed against both autochthonous and allogenic target cells in 2 of 3 experiments. However, lymphocyte cytotoxicity was greater against autochthonous cells than against allogenic target cells in 1 of 3 experiments.", "contents": "Demonstration of cytotoxic lymphocytes to virus-infected target cells in pigs inoculated with transmissible gastroenteritis virus. Lymphocytes, cytotoxic to virus-infected target cells, were induced in pigs orally exposed to transmissible gastroenteritis virus. They were studied and experiments were carried out by using autochthonous testicle cells as target cells to avoid genetic incompatibility of effector lymphocytes and target cells. Cytotoxic lymphocytes were demonstrated in Peyer's patches, mesenteric lymph nodes, spleen, and peripheral blood on postinoculation day (PID) 7. Cytotoxic activity of lymphocytes increased thereafter and reached the maximal amount at PID 21. Lymphocyte cytotoxicity was somewhat greater in lymphocytes of peripheral blood and spleen than in those of Peyer's patches and mesenteric lymph nodes after PID 14. On the contrary, lymphocyte reactivity to the viral antigen measured by lymphocyte proliferative assay was higher in Peyer's patch and mesenteric lymph node cells than in peripheral blood and splenic cells. Lymphocyte cytotoxicity was depressed by treating effector cells with anti-porcine thymocyte serum and complement. However, lymphocyte suspensions treated with anti-porcine thymocyte serum and complement were still cytotoxic to some extent against virus-infected target cells, although T lymphocytes were completely excluded by the treatment. This suggests that cytotoxic mechanism other than the direct action of cytotoxic T lymphocytes may be involved in the cytotoxicity assay systems used in the present studies. In experiments in which allogenic cells (testicle cells of siblings) were used together with autochthonous cells as targets, lymphocyte cytotoxicity was equally expressed against both autochthonous and allogenic target cells in 2 of 3 experiments. However, lymphocyte cytotoxicity was greater against autochthonous cells than against allogenic target cells in 1 of 3 experiments."}
{"id": "PMID:223477", "title": "Responses of immune and nonimmune adult rhesus macaques (Macaca mulatta) to adenovirus SV-20.", "content": "Adenovirus SV-20 (ASV-20) was inoculated subcutaneously into adult rhesus macaques (Macaca mulatta), and various immunologic parameters were studied. Similar changes were observed in macaques that had anti-ASV-20 serum-neutralizing antibodies prior to inoculation and in those lacking detectable antibodies. There were absolute decreases in numbers of peripheral blood lymphocytes (PBL), erythrocyte-rosetting lymphocytes, complement-receptor lymphocytes, and Fc-receptor lymphocytes. These changes were most significant (P less than 0.05) on postinoculation days (PID) 3 and 7. Mitogenic responsiveness to concanavalin A, phytohemagglutinin, and pokeweed mitogen in cultured PBL from immune and nonimmune macaques was depressed on PID 3, 7, and 14. Ultraviolet-inactivated ASV-20 caused moderate suppression of phytohemagglutinin-induced mitogenesis when viral particles and lectin were added simultaneously to PBL cultures. Plasma cortisol (hydrocortisone) values were not significantly altered following inoculation of ASV-20. High titers of anti-ASV-20 antibody developed by PID 7 in nonimmune macaques, and previously immune macaques showed a booster effect in the same time period. Antibody titers were still increased 120 days after inoculation. There was no clinical evidence of an adverse effect of ASV-20 infection in these macaques.", "contents": "Responses of immune and nonimmune adult rhesus macaques (Macaca mulatta) to adenovirus SV-20. Adenovirus SV-20 (ASV-20) was inoculated subcutaneously into adult rhesus macaques (Macaca mulatta), and various immunologic parameters were studied. Similar changes were observed in macaques that had anti-ASV-20 serum-neutralizing antibodies prior to inoculation and in those lacking detectable antibodies. There were absolute decreases in numbers of peripheral blood lymphocytes (PBL), erythrocyte-rosetting lymphocytes, complement-receptor lymphocytes, and Fc-receptor lymphocytes. These changes were most significant (P less than 0.05) on postinoculation days (PID) 3 and 7. Mitogenic responsiveness to concanavalin A, phytohemagglutinin, and pokeweed mitogen in cultured PBL from immune and nonimmune macaques was depressed on PID 3, 7, and 14. Ultraviolet-inactivated ASV-20 caused moderate suppression of phytohemagglutinin-induced mitogenesis when viral particles and lectin were added simultaneously to PBL cultures. Plasma cortisol (hydrocortisone) values were not significantly altered following inoculation of ASV-20. High titers of anti-ASV-20 antibody developed by PID 7 in nonimmune macaques, and previously immune macaques showed a booster effect in the same time period. Antibody titers were still increased 120 days after inoculation. There was no clinical evidence of an adverse effect of ASV-20 infection in these macaques."}
{"id": "PMID:223479", "title": "Equine infectious anemia virus: development of a simple reproducible method for titrating infectivity of the cell-adapted strain.", "content": "An equine dermal cell line between the 14th and 30th subpassages was used to develop a reproducible method of titrating the infectivity of the cell-adapted strain of equine infectious anemia virus (EIAV). Cells inoculated with EIAV were subcultured or fed once each week and were monitored for the production of P26 antigen of EIAV in supernatant fluids. Ultrathin sections were prepared once each week and were examined for the detection of budding virus-like particles (VLP). The VLP could not be detected in the infected cells subcultured once each week. When the medium was changed once week and when the cells not transferred, budding VLP were detected routinely after 3 to 4 weeks, Feeding of the infected cells once each week was used to establish the infectivity assay. The reproducibility of the assay on a frozen viral stock preparation was within an endpoint of one tenfold dilution.", "contents": "Equine infectious anemia virus: development of a simple reproducible method for titrating infectivity of the cell-adapted strain. An equine dermal cell line between the 14th and 30th subpassages was used to develop a reproducible method of titrating the infectivity of the cell-adapted strain of equine infectious anemia virus (EIAV). Cells inoculated with EIAV were subcultured or fed once each week and were monitored for the production of P26 antigen of EIAV in supernatant fluids. Ultrathin sections were prepared once each week and were examined for the detection of budding virus-like particles (VLP). The VLP could not be detected in the infected cells subcultured once each week. When the medium was changed once week and when the cells not transferred, budding VLP were detected routinely after 3 to 4 weeks, Feeding of the infected cells once each week was used to establish the infectivity assay. The reproducibility of the assay on a frozen viral stock preparation was within an endpoint of one tenfold dilution."}
{"id": "PMID:223481", "title": "Multiple granular cell tumors of the bronchi: treatment with laser.", "content": "Granular cell tumors involving multiple bronchial and extrapulmonary sites were found in a young man. Carbon dioxide laser ray was applied through a specially fitted rigid bronchoscope to a lesion at the left mainstem bronchus. Serial follow-up bronchoscopies revealed a white scarred plaque without evidence of regrowth. A partially obstructing lesion at the left lower lobe bronchus did not respond to one application of laser therapy. Laser treatment of proximal benign bronchial lesions is feasible; however, peripheral lesions may require several courses of laser therapy.", "contents": "Multiple granular cell tumors of the bronchi: treatment with laser. Granular cell tumors involving multiple bronchial and extrapulmonary sites were found in a young man. Carbon dioxide laser ray was applied through a specially fitted rigid bronchoscope to a lesion at the left mainstem bronchus. Serial follow-up bronchoscopies revealed a white scarred plaque without evidence of regrowth. A partially obstructing lesion at the left lower lobe bronchus did not respond to one application of laser therapy. Laser treatment of proximal benign bronchial lesions is feasible; however, peripheral lesions may require several courses of laser therapy."}
{"id": "PMID:223482", "title": "Pulmonary cell-mediated cytotoxicity in hamsters with parainfluenza virus type 3 pneumonia.", "content": "A 51Cr-release cytotoxic assay in vitro was developed to permit definition of the role of local pulmonary cell-mediated immunity in the recovery phase of experimental parainfluenza virus type 3 pneumonia in the Syrian hamster. Cytotoxic effector cells were obtained by bronchalveolar lavage; virus-infected targets were syngeneic secondary hamster kidney cells. Maximal target-cell killing was mediated by lung lavage cells obtained one week after infection; the response waned rapidly thereafter. There was a close temporal correlation between the cytotoxic response and termination of virus replication in the lung. Cytotoxicity was virus specific and was restricted by a requirement for species identity between effector and target cells. Immune spleen cells mediated one-fourth the amount of 51Cr release effected by lung lavage cells, which suggests that cytotoxic effectors were concentrated in the lung. Although the identity of the cytotoxic effector cell was not established conclusively, the characteristics of the response suggested strongly that thymus-derived lymphocytes mediated lysis of target cells. Further work is required to determine the relative importance of this aspect of the host response during recovery from respiratory viral infection.", "contents": "Pulmonary cell-mediated cytotoxicity in hamsters with parainfluenza virus type 3 pneumonia. A 51Cr-release cytotoxic assay in vitro was developed to permit definition of the role of local pulmonary cell-mediated immunity in the recovery phase of experimental parainfluenza virus type 3 pneumonia in the Syrian hamster. Cytotoxic effector cells were obtained by bronchalveolar lavage; virus-infected targets were syngeneic secondary hamster kidney cells. Maximal target-cell killing was mediated by lung lavage cells obtained one week after infection; the response waned rapidly thereafter. There was a close temporal correlation between the cytotoxic response and termination of virus replication in the lung. Cytotoxicity was virus specific and was restricted by a requirement for species identity between effector and target cells. Immune spleen cells mediated one-fourth the amount of 51Cr release effected by lung lavage cells, which suggests that cytotoxic effectors were concentrated in the lung. Although the identity of the cytotoxic effector cell was not established conclusively, the characteristics of the response suggested strongly that thymus-derived lymphocytes mediated lysis of target cells. Further work is required to determine the relative importance of this aspect of the host response during recovery from respiratory viral infection."}
{"id": "PMID:223483", "title": "[Sleep apnea in a child with adenotonsillar hypertrophy (author's transl)].", "content": "A three year old with sleep apnea due to adenotonsillar hypertrophy is presented. The picture improved after treatment with antibiotics and corticosteroids, and disappeared after adenotonsillectomy. The symptomatology is studied in relation to primary alveolar hypoventilation and the \"sudden death\" syndrome in infants. The need of an early diagnosis is emphasized to avoid onset of an irreversible \"cor pulmonale\". It is suggested that aside from a probable predisposing \"central\" and constitutional factor in children with this syndrome, apparently there are heterogeneous electroencephalographic sleep patterns.", "contents": "[Sleep apnea in a child with adenotonsillar hypertrophy (author's transl)]. A three year old with sleep apnea due to adenotonsillar hypertrophy is presented. The picture improved after treatment with antibiotics and corticosteroids, and disappeared after adenotonsillectomy. The symptomatology is studied in relation to primary alveolar hypoventilation and the \"sudden death\" syndrome in infants. The need of an early diagnosis is emphasized to avoid onset of an irreversible \"cor pulmonale\". It is suggested that aside from a probable predisposing \"central\" and constitutional factor in children with this syndrome, apparently there are heterogeneous electroencephalographic sleep patterns."}
{"id": "PMID:223485", "title": "Fever: pathogenesis, pathophysiology, and purpose.", "content": "Fever appears to have evolved in vertebrate hosts as an adaptive mechanism for controlling infection. This phenomenon is produced by certain exogenous (largely microbial) stimuli that activated bone-marrow-derived phagocytes to release a fever-inducing hormone (endogenous pyrogen). Endogenous pyrogen, in turn, circulates to the thermoregulatory center of the brain (preoptic area of the anterior hypothalamus) where it causes an elevation in the \"set-point\" for normal body temperature. Warm blooded animals produced fever by increasing heat production (through shivering) or reducing heat loss (by peripheral vasoconstriction), whereas cold blooded animals do so only by behavioral mechanisms (seeking a warmer environment). This paper discusses current concepts that involve the mechanism of endogenous pyrogen production, the role of central transmittors, and the probable function of fever in combating disease.", "contents": "Fever: pathogenesis, pathophysiology, and purpose. Fever appears to have evolved in vertebrate hosts as an adaptive mechanism for controlling infection. This phenomenon is produced by certain exogenous (largely microbial) stimuli that activated bone-marrow-derived phagocytes to release a fever-inducing hormone (endogenous pyrogen). Endogenous pyrogen, in turn, circulates to the thermoregulatory center of the brain (preoptic area of the anterior hypothalamus) where it causes an elevation in the \"set-point\" for normal body temperature. Warm blooded animals produced fever by increasing heat production (through shivering) or reducing heat loss (by peripheral vasoconstriction), whereas cold blooded animals do so only by behavioral mechanisms (seeking a warmer environment). This paper discusses current concepts that involve the mechanism of endogenous pyrogen production, the role of central transmittors, and the probable function of fever in combating disease."}
{"id": "PMID:223490", "title": "High-density lipoprotein, lipid, and carbohydrate metabolism during increasing fitness.", "content": "Eleven unfit bank executives in sedentary employment exercised daily for 10 weeks according to the Canadian Air-Force 5BX Exercise Programme. Over this period no changes were observed in the glucose or insulin responses to a standard breakfast or to intravenous glucose, or in the glucose response to intravenous insulin. There was a significant reduction in high-density-lipoprotein cholesterol, but total plasma triglyceride and cholesterol levels were unaffected by exercise.", "contents": "High-density lipoprotein, lipid, and carbohydrate metabolism during increasing fitness. Eleven unfit bank executives in sedentary employment exercised daily for 10 weeks according to the Canadian Air-Force 5BX Exercise Programme. Over this period no changes were observed in the glucose or insulin responses to a standard breakfast or to intravenous glucose, or in the glucose response to intravenous insulin. There was a significant reduction in high-density-lipoprotein cholesterol, but total plasma triglyceride and cholesterol levels were unaffected by exercise."}
{"id": "PMID:223487", "title": "Coexisting benign mixed tumor and mucoepidermoid carcinoma of the parotid gland.", "content": "Multiple unilateral parotid gland tumors are very rare. A review of the literature shows only seven cases of coexisting unilateral parotid tumors. This patient had a benign mixed tumor and a mucoepidermoid carcinoma of the right parotid gland. This is the eighth reported case of multiple unilateral parotid tumors and the first to show such a combination of tumors.", "contents": "Coexisting benign mixed tumor and mucoepidermoid carcinoma of the parotid gland. Multiple unilateral parotid gland tumors are very rare. A review of the literature shows only seven cases of coexisting unilateral parotid tumors. This patient had a benign mixed tumor and a mucoepidermoid carcinoma of the right parotid gland. This is the eighth reported case of multiple unilateral parotid tumors and the first to show such a combination of tumors."}
{"id": "PMID:223488", "title": "Thermal hazard during mastoid surgery.", "content": "Torque speed characteristics of two mastoid drills were measured. Potential temperature elevations in temporal bones were calculated from these measurements. Measured temperature elevations in temporal bones drilled without irrigation agreed well with predictions. Irrigation was demonstrated to be of critical importance in minimizing thermal hazard from mastoid drills.", "contents": "Thermal hazard during mastoid surgery. Torque speed characteristics of two mastoid drills were measured. Potential temperature elevations in temporal bones were calculated from these measurements. Measured temperature elevations in temporal bones drilled without irrigation agreed well with predictions. Irrigation was demonstrated to be of critical importance in minimizing thermal hazard from mastoid drills."}
{"id": "PMID:223493", "title": "Paraneoplastic vasculitis of nerve: a remote effect of cancer.", "content": "The development of mononeuritis multiplex brought three men to medical attention weeks to months prior to the diagnosis of a malignancy. In each case, sural nerve biopsy exhibited active wallerian degeneration with vasculitis. Two of the men died and at autopsy were found to have clinically unrecognized oat cell carcinoma and carcinomatous sensory neuropathy with brainstem encephalitis. The third patient is still alive but was found to have a lymphoma and has subsequently developed a liposarcoma. The vasculitis in all 3 cases seems limited mainly to the peripheral nervous system. Mononeuritis multiplex due to vasculitis may represent a new remote effect of cancer on the nervous system.", "contents": "Paraneoplastic vasculitis of nerve: a remote effect of cancer. The development of mononeuritis multiplex brought three men to medical attention weeks to months prior to the diagnosis of a malignancy. In each case, sural nerve biopsy exhibited active wallerian degeneration with vasculitis. Two of the men died and at autopsy were found to have clinically unrecognized oat cell carcinoma and carcinomatous sensory neuropathy with brainstem encephalitis. The third patient is still alive but was found to have a lymphoma and has subsequently developed a liposarcoma. The vasculitis in all 3 cases seems limited mainly to the peripheral nervous system. Mononeuritis multiplex due to vasculitis may represent a new remote effect of cancer on the nervous system."}
{"id": "PMID:223489", "title": "Cytomegalovirus isolation from a human inner ear.", "content": "Cytomegalovirus (CMV) infection of the fetus has been associated with congenital deafness or hearing loss. This association has previously been based on clinical or pathological studies. We report an infant who died with the congenital CMV syndrome in which CMV was isolated from the perilymph of the inner ear providing additional evidence that this virus can infect the labyrinth.", "contents": "Cytomegalovirus isolation from a human inner ear. Cytomegalovirus (CMV) infection of the fetus has been associated with congenital deafness or hearing loss. This association has previously been based on clinical or pathological studies. We report an infant who died with the congenital CMV syndrome in which CMV was isolated from the perilymph of the inner ear providing additional evidence that this virus can infect the labyrinth."}
{"id": "PMID:223494", "title": "Abnormal auditory evoked potentials in hereditary motor-sensory neuropathy.", "content": "From a kinship with a dominantly inherited motor-sensory neuropathy, we studied 2 brothers with brainstem auditory evoked potentials and behavioral audiometric tests. They had abnormal prolongation of I-III interpeak intervals. Wave V was poorly developed. Conventional audiometric tests did not reveal a peripheral hearing loss. It is probable that their auditory nerves and spiral ganglia are undergoing a pathophysiological process analogous to that of their peripheral nerves.", "contents": "Abnormal auditory evoked potentials in hereditary motor-sensory neuropathy. From a kinship with a dominantly inherited motor-sensory neuropathy, we studied 2 brothers with brainstem auditory evoked potentials and behavioral audiometric tests. They had abnormal prolongation of I-III interpeak intervals. Wave V was poorly developed. Conventional audiometric tests did not reveal a peripheral hearing loss. It is probable that their auditory nerves and spiral ganglia are undergoing a pathophysiological process analogous to that of their peripheral nerves."}
{"id": "PMID:223491", "title": "Immunohistochemical evidence for RNA virus related components in human breast cancer.", "content": "The localization of antigenic components with cross-reactivity to a 52,000 dalton group specific glycoprotein (gp52) of the mouse mammary tumor virus (MMTV) in paraffin sections of human breast carcinomas is described using an indirect immunoperoxidase method. This method was first optimized on paraffin sections of mouse mammary tumors. The specificity of the reaction observed in the human tissues was established by absorption of the specific IgG with: a) purified gp52; b) several relevant and irrelevant viral preparations; c) normal human plasma, leukocytes, breast tissue, milk, actin, collagen, and hyaluronic acid; d) sheep erythrocytes, bovine mucin and fetal calf serum. Only MMTV and purified gp52 eliminated the immunohistochemical reaction in human breast tumors. Positive reactions were seen in 171 of 376 (45.5 percent) randomly selected breast carcinomas of various histopathologic types, while negative reactions were obtained in all 137 normal and benign cases tested. In those invasive tumors with an intraductal component, a higher percentage (63.9 percent) of positive cases was seen. A positive reaction of different specificity was observed in foci of apocrine metaplasia. With one exception, 99 carcinomas from 13 organs other than breast and eight cystosarcomas were negative.", "contents": "Immunohistochemical evidence for RNA virus related components in human breast cancer. The localization of antigenic components with cross-reactivity to a 52,000 dalton group specific glycoprotein (gp52) of the mouse mammary tumor virus (MMTV) in paraffin sections of human breast carcinomas is described using an indirect immunoperoxidase method. This method was first optimized on paraffin sections of mouse mammary tumors. The specificity of the reaction observed in the human tissues was established by absorption of the specific IgG with: a) purified gp52; b) several relevant and irrelevant viral preparations; c) normal human plasma, leukocytes, breast tissue, milk, actin, collagen, and hyaluronic acid; d) sheep erythrocytes, bovine mucin and fetal calf serum. Only MMTV and purified gp52 eliminated the immunohistochemical reaction in human breast tumors. Positive reactions were seen in 171 of 376 (45.5 percent) randomly selected breast carcinomas of various histopathologic types, while negative reactions were obtained in all 137 normal and benign cases tested. In those invasive tumors with an intraductal component, a higher percentage (63.9 percent) of positive cases was seen. A positive reaction of different specificity was observed in foci of apocrine metaplasia. With one exception, 99 carcinomas from 13 organs other than breast and eight cystosarcomas were negative."}
{"id": "PMID:223492", "title": "Islet cell tumors of the pancreas: clinico-biochemical correlations.", "content": "Islet cell tumors produce a spectrum of syndromes. Intensive investigations of these tumors have enhanced our understanding of cellular origin, physiology and biochemistry of the islet hormones. Biochemical studies on the hormones are helpful in the diagnosis and treatment planning of the islet tumors. For example, insulinoma and glucagonoma can be diagnosed more readily by demonstration of proinsulin and proglucagon-like components, respectively, in the blood. Similarly, measurement of vasoactive intestinal polypeptide is not only useful in the diagnosis, but also in the follow-up of patients with pancreatic cholera syndrome. This mini-review examines these and other clinico-biochemical correlates seen in islet tumors.", "contents": "Islet cell tumors of the pancreas: clinico-biochemical correlations. Islet cell tumors produce a spectrum of syndromes. Intensive investigations of these tumors have enhanced our understanding of cellular origin, physiology and biochemistry of the islet hormones. Biochemical studies on the hormones are helpful in the diagnosis and treatment planning of the islet tumors. For example, insulinoma and glucagonoma can be diagnosed more readily by demonstration of proinsulin and proglucagon-like components, respectively, in the blood. Similarly, measurement of vasoactive intestinal polypeptide is not only useful in the diagnosis, but also in the follow-up of patients with pancreatic cholera syndrome. This mini-review examines these and other clinico-biochemical correlates seen in islet tumors."}
{"id": "PMID:223495", "title": "Ontogeny of spontaneous blinking and of habituation of the blink reflex.", "content": "Habituation of the blink reflex to glabellar percussion was examined in 164 infants and children from ages 2 days to 18 years and in 18 adults aged 18 to 50 years. Spontaneous blink rates were measured in 269 children and 179 adults. The mean number of glabellar taps required for habituation of the blink reflex increased from 2.7 (SD 1.2) at 0 to 2 months of age to a peak of 13.3 (SD 5.6) at age 3 to 4, remained at more than 10 until age 6, after which a rapid decline occurred, reaching the adult level of 2 to 5 blinks to habituation at age 12 years. The mean rate of spontaneous blinking was less than 2 per minute in early infancy and increased steadily during childhood up to age 14 or 15. The inverse relationship of spontaneous blink rate and number of blink reflexes to habituation in early childhood and in disorders of dopamine transmission suggests that spontaneous blink rate and habituation of the blink reflex reflect maturation and integrity of dopaminergic circuits in the brain.", "contents": "Ontogeny of spontaneous blinking and of habituation of the blink reflex. Habituation of the blink reflex to glabellar percussion was examined in 164 infants and children from ages 2 days to 18 years and in 18 adults aged 18 to 50 years. Spontaneous blink rates were measured in 269 children and 179 adults. The mean number of glabellar taps required for habituation of the blink reflex increased from 2.7 (SD 1.2) at 0 to 2 months of age to a peak of 13.3 (SD 5.6) at age 3 to 4, remained at more than 10 until age 6, after which a rapid decline occurred, reaching the adult level of 2 to 5 blinks to habituation at age 12 years. The mean rate of spontaneous blinking was less than 2 per minute in early infancy and increased steadily during childhood up to age 14 or 15. The inverse relationship of spontaneous blink rate and number of blink reflexes to habituation in early childhood and in disorders of dopamine transmission suggests that spontaneous blink rate and habituation of the blink reflex reflect maturation and integrity of dopaminergic circuits in the brain."}
{"id": "PMID:223497", "title": "[Synthesis of spin-labeled rubomycin and a study of its interaction with DNA].", "content": "Hydrochloride of 14-(I-oxyl-2,2,6,6-tetramethylpiperidyl-4)-acetoxyrubomycin (spin-labeled rubomycin or SL-rubomycin) was prepared by interaction of hydrochloride of 14-bromrubomycin with potassium salt of I-oxyl-2,2,6,6-tetramethylpiperidyl-4-acetic acid. Its interaction with DNA and synthetic poly A and poly U polyribonucleotides was studied. The character of the EPR spectra was indicative of DNA binding with SL-rubomycin and forming a system with a high level of regularity similar to that of liquid crystals. The results of the study of the EPR spectra correlated with the model of rubomycin intercalation between the pairs of DNA bases and were indicative of water surrounding of the nitroxyl group of SL-rubomycin bound with DNA.", "contents": "[Synthesis of spin-labeled rubomycin and a study of its interaction with DNA]. Hydrochloride of 14-(I-oxyl-2,2,6,6-tetramethylpiperidyl-4)-acetoxyrubomycin (spin-labeled rubomycin or SL-rubomycin) was prepared by interaction of hydrochloride of 14-bromrubomycin with potassium salt of I-oxyl-2,2,6,6-tetramethylpiperidyl-4-acetic acid. Its interaction with DNA and synthetic poly A and poly U polyribonucleotides was studied. The character of the EPR spectra was indicative of DNA binding with SL-rubomycin and forming a system with a high level of regularity similar to that of liquid crystals. The results of the study of the EPR spectra correlated with the model of rubomycin intercalation between the pairs of DNA bases and were indicative of water surrounding of the nitroxyl group of SL-rubomycin bound with DNA."}
{"id": "PMID:223498", "title": "[Pseudomonas aeruginosa melanin].", "content": "The EPR, IR, UV and visible absorption spectra of a melanin-like pigment from P. aeruginosa were studied. By the whole complex of the spectral characteristics the pigment may be classified as belonging to the melanin group. The study of the antibiotic properties of the pigment showed that it did not inhibit the growth of P. aeruginosa and E. coli. Still, it possessed some antistaphylococcal activity.", "contents": "[Pseudomonas aeruginosa melanin]. The EPR, IR, UV and visible absorption spectra of a melanin-like pigment from P. aeruginosa were studied. By the whole complex of the spectral characteristics the pigment may be classified as belonging to the melanin group. The study of the antibiotic properties of the pigment showed that it did not inhibit the growth of P. aeruginosa and E. coli. Still, it possessed some antistaphylococcal activity."}
{"id": "PMID:223499", "title": "In vitro system for studying the efficacy of antiviral agents in preventing the reactivation of latent herpes simplex virus.", "content": "Antiviral antibody and interferon did not prevent in vitro reactivation of herpes simplex virus in latently infected sensory ganglia. Phosphonoacetic acid and 9-beta-d-arabinofuranosyladenine blocked reactivation, but this treatment did not eradicate the latent infection.", "contents": "In vitro system for studying the efficacy of antiviral agents in preventing the reactivation of latent herpes simplex virus. Antiviral antibody and interferon did not prevent in vitro reactivation of herpes simplex virus in latently infected sensory ganglia. Phosphonoacetic acid and 9-beta-d-arabinofuranosyladenine blocked reactivation, but this treatment did not eradicate the latent infection."}
{"id": "PMID:223502", "title": "A new method for obtaining viable cells from dermal infiltrates. A study on 2,4 dinitrochlorobenzene induced contact dermatitis.", "content": "Experimental contact dermatitis has been induced in 2,4 dinitrochlorobenzene (DNCB) sensitized guinea pigs. The developing dermal infiltrate was excised and the infiltrating cells were obtained by mechanical extraction alone as well as by the combination with collagenase and elastase treatment. The most viable cells appeared in the elastase and mechanically extracted samples and the least in those subjected to mechanical treatment alone. The most cells in the enzyme-treated samples were present 24 h after re-exposure of the sensitized animals to DNCB consisting mainly of lymphocytes and of polymorphonuclear granulocytes. The optimum conditions for the action of enzymes including optimum duration of the treatment, buffer milieu, aspecific proteolytic effect on foreign substrate and action on T and B cell receptors have been elaborated. It was concluded that 80 min of collagenase treatment with gentle mechanical extraction under specified conditions does not affect any measurable immunologic properties of the liberated cells resulting in the second best yield. A comparison of these data with earlier reports and their significance is being discussed.", "contents": "A new method for obtaining viable cells from dermal infiltrates. A study on 2,4 dinitrochlorobenzene induced contact dermatitis. Experimental contact dermatitis has been induced in 2,4 dinitrochlorobenzene (DNCB) sensitized guinea pigs. The developing dermal infiltrate was excised and the infiltrating cells were obtained by mechanical extraction alone as well as by the combination with collagenase and elastase treatment. The most viable cells appeared in the elastase and mechanically extracted samples and the least in those subjected to mechanical treatment alone. The most cells in the enzyme-treated samples were present 24 h after re-exposure of the sensitized animals to DNCB consisting mainly of lymphocytes and of polymorphonuclear granulocytes. The optimum conditions for the action of enzymes including optimum duration of the treatment, buffer milieu, aspecific proteolytic effect on foreign substrate and action on T and B cell receptors have been elaborated. It was concluded that 80 min of collagenase treatment with gentle mechanical extraction under specified conditions does not affect any measurable immunologic properties of the liberated cells resulting in the second best yield. A comparison of these data with earlier reports and their significance is being discussed."}
{"id": "PMID:223503", "title": "DNA-binding proteins in the sera of patients with malignant melanoma.", "content": "Sera of patients with various malignancies are known to contain DNA-binding proteins (DBP) which are not present in sera of normal individuals. In this paper sera of patients with malignant melanoma (MM) were examined as to whether characteristic DBP are present, too. DBP are isolated by DNA-affinity chromatography and represent 0.5-0.9% of all serum proteins. After separation of the DBP by SDS slab gel electrophoresis no typical DBP is detectable in sera of MM-patients. However, quantitative differences are found in sera of patients in the clinical stages I-III and/or tumor level 3-5: 1. All 9 sera of patients who had clinical signs of MM contain more DBP with molecular weight (mw) of 20,000-24,000 dalton than control sera. However, these DBP are only increased in 30% of the 22 sera from MM-patients who had clinical signs for 13-73 months after tumor excision. 2. All sera of the 10 MM-patients of whom sera were drawn twice after tumor excision at an interval of 7-46 months without clinical signs, showed a reduction of DBP with mw 30,000, 68,000, and 165,000.", "contents": "DNA-binding proteins in the sera of patients with malignant melanoma. Sera of patients with various malignancies are known to contain DNA-binding proteins (DBP) which are not present in sera of normal individuals. In this paper sera of patients with malignant melanoma (MM) were examined as to whether characteristic DBP are present, too. DBP are isolated by DNA-affinity chromatography and represent 0.5-0.9% of all serum proteins. After separation of the DBP by SDS slab gel electrophoresis no typical DBP is detectable in sera of MM-patients. However, quantitative differences are found in sera of patients in the clinical stages I-III and/or tumor level 3-5: 1. All 9 sera of patients who had clinical signs of MM contain more DBP with molecular weight (mw) of 20,000-24,000 dalton than control sera. However, these DBP are only increased in 30% of the 22 sera from MM-patients who had clinical signs for 13-73 months after tumor excision. 2. All sera of the 10 MM-patients of whom sera were drawn twice after tumor excision at an interval of 7-46 months without clinical signs, showed a reduction of DBP with mw 30,000, 68,000, and 165,000."}
{"id": "PMID:223504", "title": "Effect of ACTH and corticosterone on melanogenesis and cyclic nucleotide levels in the B-16 melanoma.", "content": "The acute in vitro action of ACTH and corticosterone individually and in combination were determined in the B-16 melanoma grown in vivo. ACTH elevated levels 10-fold while tyrosinase activity generally was depressed. Corticosterone depressed cAMP levels and tyrosinase activity. ACTH in the presence of corticosterone produced a coincident peak in tyrosinase activity and cAMP levels followed by a depression of enzymatic activity. The results demonstrate that cAMP is not the sole modulator of tyrosinase activity and that ACTH, corticosterone and cAMP interact in the regulation of B-16 melanoma tyrosinase activity.", "contents": "Effect of ACTH and corticosterone on melanogenesis and cyclic nucleotide levels in the B-16 melanoma. The acute in vitro action of ACTH and corticosterone individually and in combination were determined in the B-16 melanoma grown in vivo. ACTH elevated levels 10-fold while tyrosinase activity generally was depressed. Corticosterone depressed cAMP levels and tyrosinase activity. ACTH in the presence of corticosterone produced a coincident peak in tyrosinase activity and cAMP levels followed by a depression of enzymatic activity. The results demonstrate that cAMP is not the sole modulator of tyrosinase activity and that ACTH, corticosterone and cAMP interact in the regulation of B-16 melanoma tyrosinase activity."}
{"id": "PMID:223507", "title": "Essential fatty acid deficiency in total parenteral nutrition. Detection by changes in intraocular pressure.", "content": "Essential fatty acid deficiency (EFAD) has been commonly and readily diagnosed during fat-free total parenteral nutrition (TPN), with only vague awareness of possible functional and clinical derangements secondary to essential fatty acid deficiency. Arachidonic acid is known to be a precursor for prostaglandin (PG) synthesis. Prostaglandins are known to be intermediaries between stimulus and cellular response in a variety of physiologic and pathologic processes; one would suspect therefore that EFAD would result in PG deficiency with resultant multiple derangements in functions regulated by PG. We tested this hypothesis by serially measuring intraocular pressure (IOP) in patients before and during fat-free TPN and after supplementing these patients with fat. In the eye as well as in various other organs PG are believed to act as mediators of adrenergic neurotransmission by a negative feedback mechanism. As catecholamines are potent ocular hypotensive agents, decreased levels of PG due to EFAD will cause increase in catecholamine turnover with a reduction in IOP. Two groups of patients matched as to their age, sex, nutritional status and diseases were studied. One group (control) was receiving a normal diet or fat-containing TPN while the other group was receiving fat-free TPN. IOP in the fat-free TPN group dropped from 13.7 +/- 0.4 mmHg pre-TPN to 9.3 +/- 0.5 mmHg during the first week of fat-free TPN. Within two weeks after supplementation of fat or return to normal oral diet IOP returned to 13.9 +/- 0.3 mmHg. Prostaglandin levels, which were 0.025 +/- 0.004 ng/ml pre-TPN or in control patients decreased to 0.012 +/- 0.002 ng/ml (p < 0.001) during fat-free TPN, to return to normal after fat was added to TPN regime or patients returned to normal oral diet. During fat-free TPN linoleic acid levels decreased to 40% of its initial value with a mild increase upon the addition of fat, while eicosatrienoic acid and the triene:tetraene ratio increased to 6.5 times their initial values. Arachidonic acid levels did not change during fat-free TPN or after repletion with fat. Intraocular pressure determination seem to be a simple, harmless, inexpensive, reliable and sensitive indicator of EFAD. Moreover, IOP determination represent a functional derangement which in a clinical setting lends functional credence to the biochemical changes of EFAD whose entire significance has not yet been determined. Similarly, serial IOP determinations are sensitive in detecting adequate functional repletion of EFAD. As PG are known to act as intermediaries in a variety of physiological processes it seems reasonable to assume that the change in IOP is only one of many different changes and derangements to occur as a result of PG and EFA deficiency.", "contents": "Essential fatty acid deficiency in total parenteral nutrition. Detection by changes in intraocular pressure. Essential fatty acid deficiency (EFAD) has been commonly and readily diagnosed during fat-free total parenteral nutrition (TPN), with only vague awareness of possible functional and clinical derangements secondary to essential fatty acid deficiency. Arachidonic acid is known to be a precursor for prostaglandin (PG) synthesis. Prostaglandins are known to be intermediaries between stimulus and cellular response in a variety of physiologic and pathologic processes; one would suspect therefore that EFAD would result in PG deficiency with resultant multiple derangements in functions regulated by PG. We tested this hypothesis by serially measuring intraocular pressure (IOP) in patients before and during fat-free TPN and after supplementing these patients with fat. In the eye as well as in various other organs PG are believed to act as mediators of adrenergic neurotransmission by a negative feedback mechanism. As catecholamines are potent ocular hypotensive agents, decreased levels of PG due to EFAD will cause increase in catecholamine turnover with a reduction in IOP. Two groups of patients matched as to their age, sex, nutritional status and diseases were studied. One group (control) was receiving a normal diet or fat-containing TPN while the other group was receiving fat-free TPN. IOP in the fat-free TPN group dropped from 13.7 +/- 0.4 mmHg pre-TPN to 9.3 +/- 0.5 mmHg during the first week of fat-free TPN. Within two weeks after supplementation of fat or return to normal oral diet IOP returned to 13.9 +/- 0.3 mmHg. Prostaglandin levels, which were 0.025 +/- 0.004 ng/ml pre-TPN or in control patients decreased to 0.012 +/- 0.002 ng/ml (p < 0.001) during fat-free TPN, to return to normal after fat was added to TPN regime or patients returned to normal oral diet. During fat-free TPN linoleic acid levels decreased to 40% of its initial value with a mild increase upon the addition of fat, while eicosatrienoic acid and the triene:tetraene ratio increased to 6.5 times their initial values. Arachidonic acid levels did not change during fat-free TPN or after repletion with fat. Intraocular pressure determination seem to be a simple, harmless, inexpensive, reliable and sensitive indicator of EFAD. Moreover, IOP determination represent a functional derangement which in a clinical setting lends functional credence to the biochemical changes of EFAD whose entire significance has not yet been determined. Similarly, serial IOP determinations are sensitive in detecting adequate functional repletion of EFAD. As PG are known to act as intermediaries in a variety of physiological processes it seems reasonable to assume that the change in IOP is only one of many different changes and derangements to occur as a result of PG and EFA deficiency."}
{"id": "PMID:223508", "title": "Carcinoma of the hepatic hilus. Surgical management and the case for resection.", "content": "Tumor resection for treatment of carcinoma of the hepatic hilus was preferred over routine palliative decompression at the University Hospital Center, Rennes, France, in 1974. Since then, resection has been performed on 18 patients. In seven of these patients resection proved impractical because of the extension of a neoplasm into the portal vein or liver, therefore palliative decompression was performed. In 11 patients (61%) tumor resection, followed by reconstruction of the biliary tree, was performed successfully. All the resected tumors were adenocarcinomas of the proximal bile ducts. Four patients had simple hepatic duct resection. In two patients duct resection was associated with right lobectomy, in three patients with left lobectomy, in one patient with segmentectomy, and in one patient with excision of the right branch of the hepatic artery. There were two postoperative deaths. The mean survival time for the remaining nine patients is 521 days. Five patients were alive in August 1978, at intervals ranging from 175 to 1180 days after resection. These results contrast favorably with those obtained between 1968 and 1973, during which period nine patients had palliative decompression, with three postoperative deaths and a mean survival time of 164 days for the remaining six patients.", "contents": "Carcinoma of the hepatic hilus. Surgical management and the case for resection. Tumor resection for treatment of carcinoma of the hepatic hilus was preferred over routine palliative decompression at the University Hospital Center, Rennes, France, in 1974. Since then, resection has been performed on 18 patients. In seven of these patients resection proved impractical because of the extension of a neoplasm into the portal vein or liver, therefore palliative decompression was performed. In 11 patients (61%) tumor resection, followed by reconstruction of the biliary tree, was performed successfully. All the resected tumors were adenocarcinomas of the proximal bile ducts. Four patients had simple hepatic duct resection. In two patients duct resection was associated with right lobectomy, in three patients with left lobectomy, in one patient with segmentectomy, and in one patient with excision of the right branch of the hepatic artery. There were two postoperative deaths. The mean survival time for the remaining nine patients is 521 days. Five patients were alive in August 1978, at intervals ranging from 175 to 1180 days after resection. These results contrast favorably with those obtained between 1968 and 1973, during which period nine patients had palliative decompression, with three postoperative deaths and a mean survival time of 164 days for the remaining six patients."}
{"id": "PMID:223509", "title": "Peripheral beta-receptor responsiveness in patients with essential hypertension.", "content": "Peripheral beta-adrenergic receptor sensitivity was characterized in 24 patients with essential hypertension and in 13 age-matched normotensive subjects using an isoproterenol hydrochloride bolus dose-response technique. Decreased beta-receptor responsiveness to this exogenously administered beta-agonist was observed in hypertensive patients; for an equivalent chronotropic effect, higher doses of isoproterenol were required in hypertensive subjects than in normal subjects. Among \"normal-renin\" hypertensive patients, beta-receptor responsiveness was directly related to furosemide-stimulated plasma renin activity (PRA), suggesting that independently stimulated PRA may provide an indirect estimate of endogenous beta-receptor sensitivity. Hypertensive patients whose mean arterial pressure fell at least 10 mm Hg after four weeks of treatment with hydrochlorothiazide had even further depression in beta-receptor responsiveness, whereas receptor sensitivity was unchanged in patients whose blood pressure was unaffected. Thus, it is unlikely that this decreased receptor responsiveness in patients with untreated essential hypertension is a direct consequence of elevated arterial pressure.", "contents": "Peripheral beta-receptor responsiveness in patients with essential hypertension. Peripheral beta-adrenergic receptor sensitivity was characterized in 24 patients with essential hypertension and in 13 age-matched normotensive subjects using an isoproterenol hydrochloride bolus dose-response technique. Decreased beta-receptor responsiveness to this exogenously administered beta-agonist was observed in hypertensive patients; for an equivalent chronotropic effect, higher doses of isoproterenol were required in hypertensive subjects than in normal subjects. Among \"normal-renin\" hypertensive patients, beta-receptor responsiveness was directly related to furosemide-stimulated plasma renin activity (PRA), suggesting that independently stimulated PRA may provide an indirect estimate of endogenous beta-receptor sensitivity. Hypertensive patients whose mean arterial pressure fell at least 10 mm Hg after four weeks of treatment with hydrochlorothiazide had even further depression in beta-receptor responsiveness, whereas receptor sensitivity was unchanged in patients whose blood pressure was unaffected. Thus, it is unlikely that this decreased receptor responsiveness in patients with untreated essential hypertension is a direct consequence of elevated arterial pressure."}
{"id": "PMID:223510", "title": "Plasma cell neoplasia with osteosclerotic lesions. A study of five cases and a review of the literature.", "content": "Sixty-eight patients with plasmacytic neoplasia and osteosclerotic lesions were analyzed. Men predominated in this series. Mean age was 55.3 years and 26 patients were younger than 51 years at diagnosis. Early onset of disease was statistically different from multiple myeloma in general. Thirty patients had peripheral polyneuropathy and often neurological manifestations preceded other symptoms. Skeletal pain was less common, whereas hepatomegaly, splenomegaly, and lymphadenopathy were more common than in myeloma in general. Incidence of azotemia, hypercalcemia, high ESR, and anemia was lower than in myeloma. In one fourth of the patients, the number of skeletal lesions did not exceed three. Mean survival was less than 20 months from first symptom and 12 months from diagnosis. Mortality was related sometimes to polyneuropathy. Thus, in several aspects, plasmacytic neoplasia with osteosclerotic lesions is different from the classical multiple myeloma.", "contents": "Plasma cell neoplasia with osteosclerotic lesions. A study of five cases and a review of the literature. Sixty-eight patients with plasmacytic neoplasia and osteosclerotic lesions were analyzed. Men predominated in this series. Mean age was 55.3 years and 26 patients were younger than 51 years at diagnosis. Early onset of disease was statistically different from multiple myeloma in general. Thirty patients had peripheral polyneuropathy and often neurological manifestations preceded other symptoms. Skeletal pain was less common, whereas hepatomegaly, splenomegaly, and lymphadenopathy were more common than in myeloma in general. Incidence of azotemia, hypercalcemia, high ESR, and anemia was lower than in myeloma. In one fourth of the patients, the number of skeletal lesions did not exceed three. Mean survival was less than 20 months from first symptom and 12 months from diagnosis. Mortality was related sometimes to polyneuropathy. Thus, in several aspects, plasmacytic neoplasia with osteosclerotic lesions is different from the classical multiple myeloma."}
{"id": "PMID:223505", "title": "[Virological research in acute respiratory diseases in 1976--1977 (author's transl)].", "content": "From October 1976 to June 1977 virological researches have been carried out on 5 subjects with influenza, on 302 children hospitalized in pediatric departments for respiratory illness and 94 children hospitalized in the same departments for other (non respiratory) diseases. The incidence of influenza was moderate and restricted to small epidemic episodes in school and preschool children. The isolated viruses resulted of A type, substantially similar to the prototype strains appeared from 1972 to 1975. Among children hospitalized for respiratory diseases Adenoviruses (6.8%) and, with decreasing frequency, Enteroviruses, paraifluenza viruses and RS have been also isolated. The incidence of isolation of RS virus is significantly related to bronchopneumonia cases in infants under on year of age. The incidence of significant increases of FC antibodies against influenza (A and B) viruses, RS and Myc. pneumoniae in children with bronchitis and broncho-pneumonia is also considerable. The drawing of pharyngeal swabs at different intervals from the entry to the hospital has shown that the shedding of respiratory viruses is generally very short and that hospital cross-infections may occur.", "contents": "[Virological research in acute respiratory diseases in 1976--1977 (author's transl)]. From October 1976 to June 1977 virological researches have been carried out on 5 subjects with influenza, on 302 children hospitalized in pediatric departments for respiratory illness and 94 children hospitalized in the same departments for other (non respiratory) diseases. The incidence of influenza was moderate and restricted to small epidemic episodes in school and preschool children. The isolated viruses resulted of A type, substantially similar to the prototype strains appeared from 1972 to 1975. Among children hospitalized for respiratory diseases Adenoviruses (6.8%) and, with decreasing frequency, Enteroviruses, paraifluenza viruses and RS have been also isolated. The incidence of isolation of RS virus is significantly related to bronchopneumonia cases in infants under on year of age. The incidence of significant increases of FC antibodies against influenza (A and B) viruses, RS and Myc. pneumoniae in children with bronchitis and broncho-pneumonia is also considerable. The drawing of pharyngeal swabs at different intervals from the entry to the hospital has shown that the shedding of respiratory viruses is generally very short and that hospital cross-infections may occur."}
{"id": "PMID:223512", "title": "Phosphate inhibition of secondary metabolism in Streptomyces hygroscopicus and its reversal by cyclic AMP.", "content": "Inorganic phosphate inhibited the biosynthesis of the macrolide antibiotic turimycin in different strains of Streptomyces hygroscopicus. In the wild type strain a depression was observed with increasing phosphate concentrations. A total inhibition was found at 0.1 M phosphate. In a high producing mutant a minimum of turimycin production occured when the phosphate concentration was between 5 mM and 10 mM. Above this concentration the antibiotic synthesis increased again but the production period shifted to a later period of cultivation. Addition of inorganic phosphate resulted in an initial increase of intracellular cyclic AMP content. But a second elevation characterizing the normal level of cyclic AMP throughout the growth phase was prevented by phosphate. Exogenous cyclic AMP as well as positive effectors of the adenylyl cyclase system were able to overcome the phosphate suppression. Cyclic AMP abolished the reduction of protein synthesis following phosphate addition and caused the reappearance of a protein band which may be responsible for the turimycin biosynthesis.", "contents": "Phosphate inhibition of secondary metabolism in Streptomyces hygroscopicus and its reversal by cyclic AMP. Inorganic phosphate inhibited the biosynthesis of the macrolide antibiotic turimycin in different strains of Streptomyces hygroscopicus. In the wild type strain a depression was observed with increasing phosphate concentrations. A total inhibition was found at 0.1 M phosphate. In a high producing mutant a minimum of turimycin production occured when the phosphate concentration was between 5 mM and 10 mM. Above this concentration the antibiotic synthesis increased again but the production period shifted to a later period of cultivation. Addition of inorganic phosphate resulted in an initial increase of intracellular cyclic AMP content. But a second elevation characterizing the normal level of cyclic AMP throughout the growth phase was prevented by phosphate. Exogenous cyclic AMP as well as positive effectors of the adenylyl cyclase system were able to overcome the phosphate suppression. Cyclic AMP abolished the reduction of protein synthesis following phosphate addition and caused the reappearance of a protein band which may be responsible for the turimycin biosynthesis."}
{"id": "PMID:223514", "title": "[Thrombocytic reactions in experimentally induced neoplasms (author's transl)].", "content": "Strain XVII mice with Graffi virus induced leukemia of various hematological types showed a pronounced thrombocytopenia which was severe in erythroblastic leukemia and weaker in lymphatic ones. The thrombocytic reactions shortly following Friend and Rauscher virus applications and occurred 3 weeks after birth in AKR mice are not found in Graffi virus system. A significant preleukemic thrombocytopenia did appear only 8 weeks after Graffi virus infection. The origin of both the preleukemic and the secondary thrombocytic reactions are discussed. (XVII X AKR) F1 hybrids, neonatally treated with N-nitroso-N-methylurea (NMU), resulted also in a decline in the number of thrombocytes after manifestation of leukemia. In contrast to the expection following NMU treatment a preleukemic thrombocytopenia appeared as in viral leukemogenesis too. The possibility of a co-operation of oncogenic viruses in chemical carcinogenesis is considered.", "contents": "[Thrombocytic reactions in experimentally induced neoplasms (author's transl)]. Strain XVII mice with Graffi virus induced leukemia of various hematological types showed a pronounced thrombocytopenia which was severe in erythroblastic leukemia and weaker in lymphatic ones. The thrombocytic reactions shortly following Friend and Rauscher virus applications and occurred 3 weeks after birth in AKR mice are not found in Graffi virus system. A significant preleukemic thrombocytopenia did appear only 8 weeks after Graffi virus infection. The origin of both the preleukemic and the secondary thrombocytic reactions are discussed. (XVII X AKR) F1 hybrids, neonatally treated with N-nitroso-N-methylurea (NMU), resulted also in a decline in the number of thrombocytes after manifestation of leukemia. In contrast to the expection following NMU treatment a preleukemic thrombocytopenia appeared as in viral leukemogenesis too. The possibility of a co-operation of oncogenic viruses in chemical carcinogenesis is considered."}
{"id": "PMID:223515", "title": "Electron microscope study on the bat testicular interstitial cell with special reference to the cytoplasmic crystalloid.", "content": "The testicular interstitial cell of the bat, Myotis schreibersi (Temmink), captured late in August was electron microscopically investigated. The cytoplasm of Myotis interstitial cells is packed by strikingly numerous mitochondria with many electron dense small matrix granules, endoplasmic reticulum and variable numbers of osmiophilic lipid droplets. The Myotis interstitial cell is characterized by alternate development of the SER and RER: In some Leydig cells the major part of the cytoplasm is packed by tubular SER, whereas in others this apparently is replaced by abundant free ribosomes containing sparse cisternae of the RER. These changes in the amounts of ser and RER are likely reversible and probably reflect functional alterations of Leydig cells of the bat, a hibernator. The Myotis interstitial cell possesses small cytoplasmic crystalloids composed of regularly oriented, compressed tubules, 20-28 m mu thick, which are continuous to the tubular SER (SER derived crystalloids). Type I and type II crystalloids are classified, which show, in suitable planes of section, honeycomb-like and fabric-like patterns, respectively. The Myotis Leydig cell extends cytoplasmic processes of irregular shape and long microvilli, the latter often conglomerates on the cell body or cytoplasmic processes. The entire surface of the cell including the processes is completely surrounded by a basal lamina.", "contents": "Electron microscope study on the bat testicular interstitial cell with special reference to the cytoplasmic crystalloid. The testicular interstitial cell of the bat, Myotis schreibersi (Temmink), captured late in August was electron microscopically investigated. The cytoplasm of Myotis interstitial cells is packed by strikingly numerous mitochondria with many electron dense small matrix granules, endoplasmic reticulum and variable numbers of osmiophilic lipid droplets. The Myotis interstitial cell is characterized by alternate development of the SER and RER: In some Leydig cells the major part of the cytoplasm is packed by tubular SER, whereas in others this apparently is replaced by abundant free ribosomes containing sparse cisternae of the RER. These changes in the amounts of ser and RER are likely reversible and probably reflect functional alterations of Leydig cells of the bat, a hibernator. The Myotis interstitial cell possesses small cytoplasmic crystalloids composed of regularly oriented, compressed tubules, 20-28 m mu thick, which are continuous to the tubular SER (SER derived crystalloids). Type I and type II crystalloids are classified, which show, in suitable planes of section, honeycomb-like and fabric-like patterns, respectively. The Myotis Leydig cell extends cytoplasmic processes of irregular shape and long microvilli, the latter often conglomerates on the cell body or cytoplasmic processes. The entire surface of the cell including the processes is completely surrounded by a basal lamina."}
{"id": "PMID:223516", "title": "Demonstration of alpha 1-antitrypsin in hepatomas.", "content": "Sixty-nine primary malignant hepatomas were examined for the presence of alpha 1-antitrypsin (alph 1-AT) in tumor cells using immunohistochemical methods. Twenty-eight tumors showed positivity for alpha 1-AT. The reaction was globular and PAS-positive in 12 hepatocellular tumors and thus simulated the pattern of alpha 1-AT accumulation in hepatocytes in subjects carrying the Z-gene for alpha 1-AT. In fact, eight of these 12 tumors presented this pattern in the nontumours liver tissue. In ten hepatocellular tumors the reaction was finely granular throughout the hepatocytic cytoplasm, but was present in only a small number of cells. Still fewer cells were positive in six cholangiocarcinomas. The globular alpha 1-AT in tumor cells may be genetically determined when associated with the Z-gene. A reappearance of fetal gene products may be assumed in three hepatocarcinomas with globules positive for alpha-fetoprotein as well as alpha 1-AT.", "contents": "Demonstration of alpha 1-antitrypsin in hepatomas. Sixty-nine primary malignant hepatomas were examined for the presence of alpha 1-antitrypsin (alph 1-AT) in tumor cells using immunohistochemical methods. Twenty-eight tumors showed positivity for alpha 1-AT. The reaction was globular and PAS-positive in 12 hepatocellular tumors and thus simulated the pattern of alpha 1-AT accumulation in hepatocytes in subjects carrying the Z-gene for alpha 1-AT. In fact, eight of these 12 tumors presented this pattern in the nontumours liver tissue. In ten hepatocellular tumors the reaction was finely granular throughout the hepatocytic cytoplasm, but was present in only a small number of cells. Still fewer cells were positive in six cholangiocarcinomas. The globular alpha 1-AT in tumor cells may be genetically determined when associated with the Z-gene. A reappearance of fetal gene products may be assumed in three hepatocarcinomas with globules positive for alpha-fetoprotein as well as alpha 1-AT."}
{"id": "PMID:223517", "title": "Intrasinusoidal bodies in the livers of thermally injured patients.", "content": "Acidophilic intrasinusoidal liver bodies appearing at autopsy in cases in which thermal injury occurred were examined by light microscopy using several special stains and by scanning and transmission electron microscopy. Morphologically, these bodies were found to be membrane-bound protein material that were usually present in the hepatic sinuses but were also identified in hepatocytes, spaces of Disse, and Kupffer's cells. Correlation of clinical data with pathologic findings failed to determine a specific cause for the intrasinusoidal bodies.", "contents": "Intrasinusoidal bodies in the livers of thermally injured patients. Acidophilic intrasinusoidal liver bodies appearing at autopsy in cases in which thermal injury occurred were examined by light microscopy using several special stains and by scanning and transmission electron microscopy. Morphologically, these bodies were found to be membrane-bound protein material that were usually present in the hepatic sinuses but were also identified in hepatocytes, spaces of Disse, and Kupffer's cells. Correlation of clinical data with pathologic findings failed to determine a specific cause for the intrasinusoidal bodies."}
{"id": "PMID:223518", "title": "Granular cell tumors of biliary ducts. Report of two cases and review of the literature.", "content": "There were two cases of granular cell tumor of the extrahepatic biliary system; to our knowledge, 17 have previously been reported. The initial symptoms most often are those of biliary colic. The majority of the patients are black and female. The cystic duct and the common bile duct are most commonly involved. Additional biliary pathologic disorder is present in more than half of the patients.", "contents": "Granular cell tumors of biliary ducts. Report of two cases and review of the literature. There were two cases of granular cell tumor of the extrahepatic biliary system; to our knowledge, 17 have previously been reported. The initial symptoms most often are those of biliary colic. The majority of the patients are black and female. The cystic duct and the common bile duct are most commonly involved. Additional biliary pathologic disorder is present in more than half of the patients."}
{"id": "PMID:223519", "title": "Malakoplakia of the skin. Ultrastructure and quantitative x-ray microanalysis of Michaelis-Gutmann bodies.", "content": "The etiologic agent in a case of malakoplakia of the skin was identified as Staphylococcus aureus from culture of the lesion and from ultrastructural observations. Ultrastructurally, electron-dense inclusions were observed in addition to membranous whorls and Michaelis-Gutmann (MG) bodies. These were labeled \"precalcification formations\" since they possessed an organic crystalline structure. These formations may act as nucleation centers for further incorporation of organic and inorganic material. Deposition of fine crystalline material in the outer region may occur as the structure becomes saturated with inorganic elements, thus completing formation of the MG body. Quantitative x-ray microanalysis of MG bodies demonstrated the presence of phosphorus, calcium, and iron, with average concentrations of 2.1%, 2.6%, and 0.7% by weight, respectively.", "contents": "Malakoplakia of the skin. Ultrastructure and quantitative x-ray microanalysis of Michaelis-Gutmann bodies. The etiologic agent in a case of malakoplakia of the skin was identified as Staphylococcus aureus from culture of the lesion and from ultrastructural observations. Ultrastructurally, electron-dense inclusions were observed in addition to membranous whorls and Michaelis-Gutmann (MG) bodies. These were labeled \"precalcification formations\" since they possessed an organic crystalline structure. These formations may act as nucleation centers for further incorporation of organic and inorganic material. Deposition of fine crystalline material in the outer region may occur as the structure becomes saturated with inorganic elements, thus completing formation of the MG body. Quantitative x-ray microanalysis of MG bodies demonstrated the presence of phosphorus, calcium, and iron, with average concentrations of 2.1%, 2.6%, and 0.7% by weight, respectively."}
{"id": "PMID:223522", "title": "Glioblastoma multiforme presenting as stroke: an electrophysiological and clinicopathological case report.", "content": "A 55-year-old man having hemiplegia after the sudden onset of a stroke was referred for rehabilitation. Cerebral angiography had demonstrated occlusion of the left middle cerebral artery and steroid therapy had been started. Attempted tapering of the steroid therapy on admission for rehabilitation resulted in the patient having severe headaches and confusion. Blink reflex evaluation, somatosensory cerebral evoked potential determinations and visual evoked responses were all consistent with a widespread process involving the parietal lobe of the patient's left cerebral hemisphere. Computerized axial tomography indicated an abnormality consistent with a space-occupying lesion. Craniotomy revealed the presence of a glioblastoma multiforme in the left cerebral hemisphere. Electrodiagnostic evaluation was entirely consistent with the operative finding of widespread involvement of the patient's left parietal lobe. Stroke patients whose conditions deteriorate over time must be serially evaluated in order to determine possible other causes of their symptoms.", "contents": "Glioblastoma multiforme presenting as stroke: an electrophysiological and clinicopathological case report. A 55-year-old man having hemiplegia after the sudden onset of a stroke was referred for rehabilitation. Cerebral angiography had demonstrated occlusion of the left middle cerebral artery and steroid therapy had been started. Attempted tapering of the steroid therapy on admission for rehabilitation resulted in the patient having severe headaches and confusion. Blink reflex evaluation, somatosensory cerebral evoked potential determinations and visual evoked responses were all consistent with a widespread process involving the parietal lobe of the patient's left cerebral hemisphere. Computerized axial tomography indicated an abnormality consistent with a space-occupying lesion. Craniotomy revealed the presence of a glioblastoma multiforme in the left cerebral hemisphere. Electrodiagnostic evaluation was entirely consistent with the operative finding of widespread involvement of the patient's left parietal lobe. Stroke patients whose conditions deteriorate over time must be serially evaluated in order to determine possible other causes of their symptoms."}
{"id": "PMID:223525", "title": "Organotropic mutagenesis in tissues of Chinese hamsters induced by chemical carcinogens.", "content": "In order to investigate the relationship between mutation and carcinogenesis in vivo, a method has been developed in which somatic mutation can be studied in specific organs of Chinese hamsters after acute dosing with chemical carcinogens. In preliminary experiments an increase in mutation was detected in cultures derived from lung tissue of hamsters after intraperitoneal dosing with the direct-acting mutagen and weak carcinogen, ethyl methanesulphonate, or with diethylnitrosamine, a carcinogen which requires metabolic activation before mutagenic activity can be demonstrated in vitro. Subsequent experiments have shown the induction of mutation in cells dereived from the bladder of animals dosed with diethylnitrosamine or methyl nitrosourea and in a variety of tissues from animals dosed with methane-sulphonates, 2-acetylaminofluorene and 3-methylcholanthrene.", "contents": "Organotropic mutagenesis in tissues of Chinese hamsters induced by chemical carcinogens. In order to investigate the relationship between mutation and carcinogenesis in vivo, a method has been developed in which somatic mutation can be studied in specific organs of Chinese hamsters after acute dosing with chemical carcinogens. In preliminary experiments an increase in mutation was detected in cultures derived from lung tissue of hamsters after intraperitoneal dosing with the direct-acting mutagen and weak carcinogen, ethyl methanesulphonate, or with diethylnitrosamine, a carcinogen which requires metabolic activation before mutagenic activity can be demonstrated in vitro. Subsequent experiments have shown the induction of mutation in cells dereived from the bladder of animals dosed with diethylnitrosamine or methyl nitrosourea and in a variety of tissues from animals dosed with methane-sulphonates, 2-acetylaminofluorene and 3-methylcholanthrene."}
{"id": "PMID:223523", "title": "[Carcinoma of the ileo-cecal appendix].", "content": "A structurally impaired appendix observed during laparotomy in a woman of 62, suffering from gall stones with stenosis of the papilla, was removed. Histological examination showed carcinoma. Right hemicolectomy was performed later.", "contents": "[Carcinoma of the ileo-cecal appendix]. A structurally impaired appendix observed during laparotomy in a woman of 62, suffering from gall stones with stenosis of the papilla, was removed. Histological examination showed carcinoma. Right hemicolectomy was performed later."}
{"id": "PMID:223526", "title": "Effect of intratracheal and oral application of corticosteroids on the adrenal function test in beagle dogs after ACTH-stimulation.", "content": "The effect of synthetic corticosteroids given intratracheally or orally on the adrenal glands of beagle dogs was investigated. The adrenal function was evaluated using a standardized ACTH stimulation test. In addition, histological and morphometrical examinations of the adrenal cortex were performed at the end of the study. Beclomethasone dipropionate given intratracheally at daily dose levels of 0.05, 0.1 and 0.5 mg/kg body weight led to a dose dependent adrenal suppression on the basis of plasma cortisol concentration and eosinophil counts after ACTH stimulation and size of zona fasciculata and reticularis. A complete adrenal suppression was observed at the highest dose level of 0.5 mg/kg body weight. Also the oral administration of 0.1 mg/kg body weight/day of beclomethasone dipropionate had a definite adrenal suppressive effect comparaable to that of 0.1 mg/kg body weight given intratracheally. However, intratracheal administration of fluocortin butylester, a local antiinflammatory drug but systemically a nearly ineffective corticosteroid (2 X 8 mg/kg body weight/day) had no suppressive effect on the adrenal gland of the beagle dog, even after a 320 times higher dose.", "contents": "Effect of intratracheal and oral application of corticosteroids on the adrenal function test in beagle dogs after ACTH-stimulation. The effect of synthetic corticosteroids given intratracheally or orally on the adrenal glands of beagle dogs was investigated. The adrenal function was evaluated using a standardized ACTH stimulation test. In addition, histological and morphometrical examinations of the adrenal cortex were performed at the end of the study. Beclomethasone dipropionate given intratracheally at daily dose levels of 0.05, 0.1 and 0.5 mg/kg body weight led to a dose dependent adrenal suppression on the basis of plasma cortisol concentration and eosinophil counts after ACTH stimulation and size of zona fasciculata and reticularis. A complete adrenal suppression was observed at the highest dose level of 0.5 mg/kg body weight. Also the oral administration of 0.1 mg/kg body weight/day of beclomethasone dipropionate had a definite adrenal suppressive effect comparaable to that of 0.1 mg/kg body weight given intratracheally. However, intratracheal administration of fluocortin butylester, a local antiinflammatory drug but systemically a nearly ineffective corticosteroid (2 X 8 mg/kg body weight/day) had no suppressive effect on the adrenal gland of the beagle dog, even after a 320 times higher dose."}
{"id": "PMID:223527", "title": "Unscheduled DNA synthesis in male rabbit germ cells induced by methylmethane sulfonate, cyclophosphamide and adriamycin.", "content": "Male rabbit germ cells were labelled by intratesticular injection of [3H]-thymidine (3H-T). In sperms of control animals, radioactivity was first demonstrated between the 40th and 43rd day after labelling, corresponding to preleptotene spermatocytes. In rabbits treated with 22.5 mg/kg methylmethane sulfonate (MMS), significant radioactivity was shown in sperms collected from day 19 ownwards. These cells derived from spermatocyes and early spermatids at the time of labelling. 3H-T incorporation into these cell populations represents unscheduled DNA synthesis (UDS), a repair process initiated after chemical damage of germ cell DNA. After i.v. injection of 20 mg/kg cyclophosphamide, an alkylating agent that must be activated, labelled sperms were found 28--37 days after treatment. This shows that UDS took place in spermatocytes during the pachytene and zygotene stages. Adriamycin (1.0 and 3.0 mg/kg) induced UDS during pachytene and zygotene stages of spermatogenesis. Sperm counts decreased during spermatogonial stages by a factor of about ten in cyclophosphamide and adriamycin treated rabbits. It was not changed after MMS-treatment.", "contents": "Unscheduled DNA synthesis in male rabbit germ cells induced by methylmethane sulfonate, cyclophosphamide and adriamycin. Male rabbit germ cells were labelled by intratesticular injection of [3H]-thymidine (3H-T). In sperms of control animals, radioactivity was first demonstrated between the 40th and 43rd day after labelling, corresponding to preleptotene spermatocytes. In rabbits treated with 22.5 mg/kg methylmethane sulfonate (MMS), significant radioactivity was shown in sperms collected from day 19 ownwards. These cells derived from spermatocyes and early spermatids at the time of labelling. 3H-T incorporation into these cell populations represents unscheduled DNA synthesis (UDS), a repair process initiated after chemical damage of germ cell DNA. After i.v. injection of 20 mg/kg cyclophosphamide, an alkylating agent that must be activated, labelled sperms were found 28--37 days after treatment. This shows that UDS took place in spermatocytes during the pachytene and zygotene stages. Adriamycin (1.0 and 3.0 mg/kg) induced UDS during pachytene and zygotene stages of spermatogenesis. Sperm counts decreased during spermatogonial stages by a factor of about ten in cyclophosphamide and adriamycin treated rabbits. It was not changed after MMS-treatment."}
{"id": "PMID:223530", "title": "Granular cell tumor (myoblastoma) of the orbit.", "content": "A 43-year-old woman had a three-month history of increasing proptosis and visual loss secondary to an inferior orbital mass. Surgical exploration revealed an encapsulated mass that was excised with good visual recovery. Light microscopy as well as electron microscopy confirmed the diagnosis of granular cell myoblastoma. The tumor's location within the orbit was unusual and its histologic origin was uncertain.", "contents": "Granular cell tumor (myoblastoma) of the orbit. A 43-year-old woman had a three-month history of increasing proptosis and visual loss secondary to an inferior orbital mass. Surgical exploration revealed an encapsulated mass that was excised with good visual recovery. Light microscopy as well as electron microscopy confirmed the diagnosis of granular cell myoblastoma. The tumor's location within the orbit was unusual and its histologic origin was uncertain."}
{"id": "PMID:223531", "title": "Herpetic ganglionic latency. Aciclovir and vidarabine therapy.", "content": "This study report the therapeutic efficacy of systemic antiviral drugs in reducing the incidence of trigeminal ganglionic latent herpes simplex virus (HSV) after ocular infection in mice. Aciclovir sodium, 60 mg/kg daily for five days starting three and 24 hours after inoculation, resulted in a significant decrease in recovery of latent HSV, 28% and 54% positive, respectively, in comparison to untreated controls, 100% positive. Initiation of similar therapy three weeks after inoculation for 5, 10, and 15 days resulted in progressive decrease in persistence of latent virus, being 100%, 33%, and 12% positive, respectively. Systemic vidarabine, 50 mg/kg daily for 15 days starting three weeks after inoculation, also resulted in a significant decrease of positive ganglionic cultures (60% positive) in comparison to the untreated controls. The results indicate that replication of HSV in the trigeminal ganglia in mice is probably continuous and that this reservoir of recurrent ocular herpes is amenable to therapy with systemic antiviral agents.", "contents": "Herpetic ganglionic latency. Aciclovir and vidarabine therapy. This study report the therapeutic efficacy of systemic antiviral drugs in reducing the incidence of trigeminal ganglionic latent herpes simplex virus (HSV) after ocular infection in mice. Aciclovir sodium, 60 mg/kg daily for five days starting three and 24 hours after inoculation, resulted in a significant decrease in recovery of latent HSV, 28% and 54% positive, respectively, in comparison to untreated controls, 100% positive. Initiation of similar therapy three weeks after inoculation for 5, 10, and 15 days resulted in progressive decrease in persistence of latent virus, being 100%, 33%, and 12% positive, respectively. Systemic vidarabine, 50 mg/kg daily for 15 days starting three weeks after inoculation, also resulted in a significant decrease of positive ganglionic cultures (60% positive) in comparison to the untreated controls. The results indicate that replication of HSV in the trigeminal ganglia in mice is probably continuous and that this reservoir of recurrent ocular herpes is amenable to therapy with systemic antiviral agents."}
{"id": "PMID:223532", "title": "Herpetic eye disease in rabbits after inoculation of autonomic ganglia.", "content": "Since herpes simplex virus (HSV) can cause persistent infection of autonomic ganglia of both humans and experimentally infected animals, we followed the pattern of eye disease and viral growth after HSV inoculation of one superior cervical ganglion in rabbits. Of 27 inoculated animals, eye disease or detectable virus developed in 18. Anterior uveitis was the most common clinical manifestation (94%), but conjunctivitis and dendritic keratitis were also frequent (60%). All 12 uveal-retinal specimens tested and five of seven ipsilateral superior cervical ganglia had detectable virus. If recurrent herpetic iritis in humans is associated with persistent infection of the superior cervical ganglion, autonomic mediators might trigger episodes of virus shedding. In patients with herpetic iritis, then, the use of epinephrine and other adrenergic agonists or antagonists should be avoided.", "contents": "Herpetic eye disease in rabbits after inoculation of autonomic ganglia. Since herpes simplex virus (HSV) can cause persistent infection of autonomic ganglia of both humans and experimentally infected animals, we followed the pattern of eye disease and viral growth after HSV inoculation of one superior cervical ganglion in rabbits. Of 27 inoculated animals, eye disease or detectable virus developed in 18. Anterior uveitis was the most common clinical manifestation (94%), but conjunctivitis and dendritic keratitis were also frequent (60%). All 12 uveal-retinal specimens tested and five of seven ipsilateral superior cervical ganglia had detectable virus. If recurrent herpetic iritis in humans is associated with persistent infection of the superior cervical ganglion, autonomic mediators might trigger episodes of virus shedding. In patients with herpetic iritis, then, the use of epinephrine and other adrenergic agonists or antagonists should be avoided."}
{"id": "PMID:223534", "title": "Clinical observations on 600 cases of recurrent laryngeal nerve paralysis.", "content": "A statistical review was made on 600 cases of recurrent laryngeal nerve paralysis who visited the author's clinic during the last 16 years. The yearly incidence, the age and sex distributions and the classifications of the causes of paralysis were presented and discussed. A special attention was given to the topics of associated laryngeal paralysis, bilateral recurrent laryngeal nerve paralysis and the so-called epidemic paralysis. A brief comment was also made on diagnosis and treatment of recurrent laryngeal nerve paralysis in general.", "contents": "Clinical observations on 600 cases of recurrent laryngeal nerve paralysis. A statistical review was made on 600 cases of recurrent laryngeal nerve paralysis who visited the author's clinic during the last 16 years. The yearly incidence, the age and sex distributions and the classifications of the causes of paralysis were presented and discussed. A special attention was given to the topics of associated laryngeal paralysis, bilateral recurrent laryngeal nerve paralysis and the so-called epidemic paralysis. A brief comment was also made on diagnosis and treatment of recurrent laryngeal nerve paralysis in general."}
{"id": "PMID:223535", "title": "Growth failure, somatomedin and growth hormone levels in juvenile diabetes mellitus--a pilot study.", "content": "Growth hormone (hGH) responsiveness to exercise and somatomedin C (SmC) activity were measured in ten children with insulin-deficient diabetes mellitus. Four of the ten children showed a significant degree of growth retardation. Normal SmC activity was found in association with elevated hGH levels. The hypothesis that growth-retarded diabetics have a failure of Sm production despite high hGH levels (analogous to malnutrition and Laron dwarfism) was not substantiated by this study. Chronic deficiency of insulin, itself a somatomedin, may play a major role in diabetic growth failure.", "contents": "Growth failure, somatomedin and growth hormone levels in juvenile diabetes mellitus--a pilot study. Growth hormone (hGH) responsiveness to exercise and somatomedin C (SmC) activity were measured in ten children with insulin-deficient diabetes mellitus. Four of the ten children showed a significant degree of growth retardation. Normal SmC activity was found in association with elevated hGH levels. The hypothesis that growth-retarded diabetics have a failure of Sm production despite high hGH levels (analogous to malnutrition and Laron dwarfism) was not substantiated by this study. Chronic deficiency of insulin, itself a somatomedin, may play a major role in diabetic growth failure."}
{"id": "PMID:223536", "title": "Liver disease associated with chronic arsenic ingestion.", "content": "The association of chronic liver disease with long-standing arsenic ingestion is well documented, although the spectrum and incidence of liver disease due to arsenic remain uncertain. We report two patients with chronic liver disease and arsenical skin changes that followed previous chronic arsenic ingestion. One patient developed macronodular cirrhosis and the other non-cirrhotic portal hypertension with perisinusoidal fibrosis. The latter patient developed a primary liver cell cancer. There is only one previously reported case of malignant hepatoma in a non-cirrhotic liver complicating chronic arsenicism. Lack of awareness of this uncommon but well described cause of chronic liver disease may account for a small proportion of patients with \"cryptogenic\" liver disease. Previous arsenic administration should be considered as a cause of chronic liver disease, especially when typical skin changes or internal neoplasia develop.", "contents": "Liver disease associated with chronic arsenic ingestion. The association of chronic liver disease with long-standing arsenic ingestion is well documented, although the spectrum and incidence of liver disease due to arsenic remain uncertain. We report two patients with chronic liver disease and arsenical skin changes that followed previous chronic arsenic ingestion. One patient developed macronodular cirrhosis and the other non-cirrhotic portal hypertension with perisinusoidal fibrosis. The latter patient developed a primary liver cell cancer. There is only one previously reported case of malignant hepatoma in a non-cirrhotic liver complicating chronic arsenicism. Lack of awareness of this uncommon but well described cause of chronic liver disease may account for a small proportion of patients with \"cryptogenic\" liver disease. Previous arsenic administration should be considered as a cause of chronic liver disease, especially when typical skin changes or internal neoplasia develop."}
{"id": "PMID:223537", "title": "Reverse phase passive haemagglutination and single radial immunodiffusion to detect epsilon antigen of Clostridium perfringens type D.", "content": "Two in vitro immunological assays were developed for detection of the epsilon (epsilon) antigen of Cl. perfringens type D. It was found that the reverse phase passive haemagglutination assay (RPHA) was able to detect concentrations of epsilon-antigen as low as 6 x 10-7 mg/ml whereas the single radial immunodiffusion techniques (SRID) was capable of detecting concentrations of epsilon-antigen above 0.01 mg/ml. When applied to gut contents from freshly dead infected sheep the RPHA test was found to be more sensitive than mouse toxicity assay in detecting the presence of epsilon-antigen. However, very low titres were detected in gut contents from normal sheep which meant that in a diagnostic situation interpretation of RPHA titres would be difficult. No epsilon-antigen was detected by SRID in gut contents from normal sheep or in gut contents from freshly dead infected sheep. The SRID assay could detect epsilon-antigen in gut contents from infected sheep allowed to decompose for 20 h post-mortem.", "contents": "Reverse phase passive haemagglutination and single radial immunodiffusion to detect epsilon antigen of Clostridium perfringens type D. Two in vitro immunological assays were developed for detection of the epsilon (epsilon) antigen of Cl. perfringens type D. It was found that the reverse phase passive haemagglutination assay (RPHA) was able to detect concentrations of epsilon-antigen as low as 6 x 10-7 mg/ml whereas the single radial immunodiffusion techniques (SRID) was capable of detecting concentrations of epsilon-antigen above 0.01 mg/ml. When applied to gut contents from freshly dead infected sheep the RPHA test was found to be more sensitive than mouse toxicity assay in detecting the presence of epsilon-antigen. However, very low titres were detected in gut contents from normal sheep which meant that in a diagnostic situation interpretation of RPHA titres would be difficult. No epsilon-antigen was detected by SRID in gut contents from normal sheep or in gut contents from freshly dead infected sheep. The SRID assay could detect epsilon-antigen in gut contents from infected sheep allowed to decompose for 20 h post-mortem."}
{"id": "PMID:223539", "title": "Infection studies on a reticuloendotheliosis virus contaminant of a commercial Marek's disease vaccine.", "content": "Reticuloendotheliosis virus (REV) was isolated in cell cultures from commercial Marek's disease (herpesvirus of turkeys) vaccine and re-isolated from the organs of vaccinated chickens. Runting and feathering abnormalities were produced when 1-day-old specific pathogen free chickens were inoculated with REV. Histopathological lesions in infected chickens were hypoplasia of the thymus, bursa and spleen, and inflammation of the proventriculus, kidneys and liver. Serological responses to REV were detected by the indirect immunoflorescence test in chickens directly inoculated with contaminated vaccine, and spread of REV infection to in-contact chickens was demonstrated by histopathological and serological investigations.", "contents": "Infection studies on a reticuloendotheliosis virus contaminant of a commercial Marek's disease vaccine. Reticuloendotheliosis virus (REV) was isolated in cell cultures from commercial Marek's disease (herpesvirus of turkeys) vaccine and re-isolated from the organs of vaccinated chickens. Runting and feathering abnormalities were produced when 1-day-old specific pathogen free chickens were inoculated with REV. Histopathological lesions in infected chickens were hypoplasia of the thymus, bursa and spleen, and inflammation of the proventriculus, kidneys and liver. Serological responses to REV were detected by the indirect immunoflorescence test in chickens directly inoculated with contaminated vaccine, and spread of REV infection to in-contact chickens was demonstrated by histopathological and serological investigations."}
{"id": "PMID:223540", "title": "Poxvirus infection of the skin of an eastern grey kangaroo.", "content": "A solitary cutaneous papillomatous lesion, present for 6 weeks, was surgically removed from the hind limb of an 18-month old eastern grey kangaroo (Macropus giganteus). The lesion did not recur within 6 months of excision. Poxvirus particles were demonstrated in epidermal cells of the lesion by electron microscopy.", "contents": "Poxvirus infection of the skin of an eastern grey kangaroo. A solitary cutaneous papillomatous lesion, present for 6 weeks, was surgically removed from the hind limb of an 18-month old eastern grey kangaroo (Macropus giganteus). The lesion did not recur within 6 months of excision. Poxvirus particles were demonstrated in epidermal cells of the lesion by electron microscopy."}
{"id": "PMID:223577", "title": "Quantification of human plasma inorganic pyrophosphate. I. Normal values in osteoarthritis and calcium pyrophosphate dihydrate crystal deposition disease.", "content": "The methodologic variables of the UDPG pyrophosphorylase method for analysis of inorganic pyrophosphate (PPi) levels in biologic fluids are described. Use of a tourniquet in collection of blood specimens elevated plasma PPi levels from 35% to 55% above control values and may explain the differences in published normal values. The sodium pyrophosphate decahydrate used to prepare the standard solution lost 8 waters of hydration after dessication, which could result in the calculation of spuriously elevated PPi levels. Normal plasma PPi concentration was 2.18 muM with a range (95% confidence limits) of 0.58-3.78 muM. Comparison of plasma PPi in normal subjects, patients with primary osteoarthritis, and patients with calcium pyrophosphate dihydrate deposition disease revealed no significant intergroup differences.", "contents": "Quantification of human plasma inorganic pyrophosphate. I. Normal values in osteoarthritis and calcium pyrophosphate dihydrate crystal deposition disease. The methodologic variables of the UDPG pyrophosphorylase method for analysis of inorganic pyrophosphate (PPi) levels in biologic fluids are described. Use of a tourniquet in collection of blood specimens elevated plasma PPi levels from 35% to 55% above control values and may explain the differences in published normal values. The sodium pyrophosphate decahydrate used to prepare the standard solution lost 8 waters of hydration after dessication, which could result in the calculation of spuriously elevated PPi levels. Normal plasma PPi concentration was 2.18 muM with a range (95% confidence limits) of 0.58-3.78 muM. Comparison of plasma PPi in normal subjects, patients with primary osteoarthritis, and patients with calcium pyrophosphate dihydrate deposition disease revealed no significant intergroup differences."}
{"id": "PMID:223578", "title": "Quantification of human plasma inorganic pyrophosphate. II. Biologic variables.", "content": "Plasma inorganic pyrophosphate (PPi) levels rose predictably (28%) after vigorous systemic exercise and returned to baseline values after 30 minutes of rest. Plasma PPi levels were greater (36%) in femoral venous blood than in femoral arterial blood. Forearm muscular exercise, however, did not result in a detectable rise in plasma PPi levels in antecubital veins. The physiologic reasons for both the systemic exercise effect and the arteriovenous differences remain unknown. Measurement of plasma PPi for 10 consecutive days in a single normal subject under basal conditions, where these and other previously identified biologic variables (fasting and diurnal variation) were controlled, showed a coefficient of variation of 12.7%. Thus biologic variability contributed less to observed variation in plasma PPi than did methodologic errors (coefficient of variation of method = 8%). The striking reproducibility of plasma PPi in this subject suggests that this important metabolite is under rather tight homeostatic control.", "contents": "Quantification of human plasma inorganic pyrophosphate. II. Biologic variables. Plasma inorganic pyrophosphate (PPi) levels rose predictably (28%) after vigorous systemic exercise and returned to baseline values after 30 minutes of rest. Plasma PPi levels were greater (36%) in femoral venous blood than in femoral arterial blood. Forearm muscular exercise, however, did not result in a detectable rise in plasma PPi levels in antecubital veins. The physiologic reasons for both the systemic exercise effect and the arteriovenous differences remain unknown. Measurement of plasma PPi for 10 consecutive days in a single normal subject under basal conditions, where these and other previously identified biologic variables (fasting and diurnal variation) were controlled, showed a coefficient of variation of 12.7%. Thus biologic variability contributed less to observed variation in plasma PPi than did methodologic errors (coefficient of variation of method = 8%). The striking reproducibility of plasma PPi in this subject suggests that this important metabolite is under rather tight homeostatic control."}
{"id": "PMID:223579", "title": "[The possibility of endorphins playing a role in psychic disturbances].", "content": "1. The release of endorphins appears to play a role as a reserve-mechanism in stress situations. 2. The application of high doses of the specific opiate antagonist 12-allyl-7,7a,8,9-tetrahydro-3,7a-dihydroxy-(4aH)-(8,9-c)-iminoethanophenanthro(4,5-b,c,d)furan-5(6H)-one (naloxone) to schizophrenic patients induces a partial reversal of hallucinations and actual delusional experience within 2--7 h after injection. 3. The blockade of opiate receptors by naloxone is possibly also effective against catatonic states of schizophrenia. 4. In affective psychoses no curative action of naloxone could be detected so far.", "contents": "[The possibility of endorphins playing a role in psychic disturbances]. 1. The release of endorphins appears to play a role as a reserve-mechanism in stress situations. 2. The application of high doses of the specific opiate antagonist 12-allyl-7,7a,8,9-tetrahydro-3,7a-dihydroxy-(4aH)-(8,9-c)-iminoethanophenanthro(4,5-b,c,d)furan-5(6H)-one (naloxone) to schizophrenic patients induces a partial reversal of hallucinations and actual delusional experience within 2--7 h after injection. 3. The blockade of opiate receptors by naloxone is possibly also effective against catatonic states of schizophrenia. 4. In affective psychoses no curative action of naloxone could be detected so far."}
{"id": "PMID:223580", "title": "[Possible consequence of ACTH-like peptides for human mental performance (author's transl)].", "content": "ACTH affects behavior of rats. The results of the reported experiments suggest that ACTH effects on conditioned behavior are the result of an improved motivation or attention. The ACTH fragments, ACTH 4--10 and ACTH 4--9, have the behavioral effects of ACTH but are devoid of endocrine activities. The ACTH 4--9 analog H-Met(O2)-Glu-His-Phe-D-Lys-Phe-OH (Org 2766) has behavioral activity after oral administration. ACTH-like-peptides restore the behavioral deficiencies of hypophysectomised rats and delay extinction of conditioned behavior of normal rats independent of the type of conditioning. So is extinction of pole jump avoidance and extinction of conditioned tast aversion delayed after Org 2766. Moreover ACTH-like peptides reduce the behavioral deficit in rats with amnesia even when the treatment is given two weeks after the induction of amnesia. In man the administration of a single dose of ACTH 4--10 on Org 2766 reduces the duration of lapses as well as the number of errors of volunteers in a continuous performance task. These and similar observations suggest that ACTH-like peptides may be of practical consequence for the therapy of patients with impairments of cognitive processes.", "contents": "[Possible consequence of ACTH-like peptides for human mental performance (author's transl)]. ACTH affects behavior of rats. The results of the reported experiments suggest that ACTH effects on conditioned behavior are the result of an improved motivation or attention. The ACTH fragments, ACTH 4--10 and ACTH 4--9, have the behavioral effects of ACTH but are devoid of endocrine activities. The ACTH 4--9 analog H-Met(O2)-Glu-His-Phe-D-Lys-Phe-OH (Org 2766) has behavioral activity after oral administration. ACTH-like-peptides restore the behavioral deficiencies of hypophysectomised rats and delay extinction of conditioned behavior of normal rats independent of the type of conditioning. So is extinction of pole jump avoidance and extinction of conditioned tast aversion delayed after Org 2766. Moreover ACTH-like peptides reduce the behavioral deficit in rats with amnesia even when the treatment is given two weeks after the induction of amnesia. In man the administration of a single dose of ACTH 4--10 on Org 2766 reduces the duration of lapses as well as the number of errors of volunteers in a continuous performance task. These and similar observations suggest that ACTH-like peptides may be of practical consequence for the therapy of patients with impairments of cognitive processes."}
{"id": "PMID:223581", "title": "Effect of ACTH on the relaxation of guinea pig trachea with various bronchodilators.", "content": "The effect of ACTH on the actions of various bronchodilators was examined using the isolated guinea pig tracheal smooth muscle. Relaxing effects of isolated guinea pig tracheal smooth muscle with 1-isoproterenol hydrochloride, salbutamol hemisulfate, hexoprenaline hydrochloride and epinephrine except prostaglandin E2 and aminophylline were markedly potentiated by combining ACTH. These results may suggest that ACTH has a direct effect on guinea pig tracheal smooth muscle by potentiating the actions of various beta-receptor stimulators.", "contents": "Effect of ACTH on the relaxation of guinea pig trachea with various bronchodilators. The effect of ACTH on the actions of various bronchodilators was examined using the isolated guinea pig tracheal smooth muscle. Relaxing effects of isolated guinea pig tracheal smooth muscle with 1-isoproterenol hydrochloride, salbutamol hemisulfate, hexoprenaline hydrochloride and epinephrine except prostaglandin E2 and aminophylline were markedly potentiated by combining ACTH. These results may suggest that ACTH has a direct effect on guinea pig tracheal smooth muscle by potentiating the actions of various beta-receptor stimulators."}
{"id": "PMID:223582", "title": "High density lipoproteinemia due to vigorous physical work inhibits the incorporation of [3H]thymidine and the synthesis of glycosaminoglycans by human aortic smooth muscle cells in culture.", "content": "The effect of sera from normolipidemic men engaging in normal physical activity and from high density lipoproteinemic lumberjacks engaging in vigorous physical activity on the incorporation of [3H]thymidine and the synthesis of glycosaminoglycans by human aortic smooth muscle cells in culture was measured. At high concentration (15%) high density lipoproteinemic serum inhibited significantly (P less than 0.001) the incorporation of thymidine. The serum inhibited the synthesis of glycosaminoglycans at all concentrations tested (1--15%) with the most marked inhibition at 10 and 15%. At lower concentrations (1--5%) the inhibition was more pronounced for sulphated glycosaminoglycans than for hyaluronic acid. The inhibition was of the same magnitude for the subclasses (chondroitin, dermatan and heparan sulphates) of sulphated glycosaminoglycans studied. High density lipoproteinemia due to vigorous physical work is postulated as a protective factor against the early biochemical reactions of arterial smooth muscle cells in the development of atherosclerosis.", "contents": "High density lipoproteinemia due to vigorous physical work inhibits the incorporation of [3H]thymidine and the synthesis of glycosaminoglycans by human aortic smooth muscle cells in culture. The effect of sera from normolipidemic men engaging in normal physical activity and from high density lipoproteinemic lumberjacks engaging in vigorous physical activity on the incorporation of [3H]thymidine and the synthesis of glycosaminoglycans by human aortic smooth muscle cells in culture was measured. At high concentration (15%) high density lipoproteinemic serum inhibited significantly (P less than 0.001) the incorporation of thymidine. The serum inhibited the synthesis of glycosaminoglycans at all concentrations tested (1--15%) with the most marked inhibition at 10 and 15%. At lower concentrations (1--5%) the inhibition was more pronounced for sulphated glycosaminoglycans than for hyaluronic acid. The inhibition was of the same magnitude for the subclasses (chondroitin, dermatan and heparan sulphates) of sulphated glycosaminoglycans studied. High density lipoproteinemia due to vigorous physical work is postulated as a protective factor against the early biochemical reactions of arterial smooth muscle cells in the development of atherosclerosis."}
{"id": "PMID:223583", "title": "Triglyceride removal from very low density lipoproteins in vivo as a function of their triglyceride content.", "content": "Rabbit very low density lipoproteins (VLDL) were fractionated in 3 subfractions differing in density and triglyceride (TG) content. The fraction of total weight represented by triglycerides was: VLDL1 TG = 71%, VLDL2 TG = 62%, VLDL3 TG = 55%. No other difference in composition was observed. After intravenous administration of radioglycerol all subfractions were labelled and the distribution of radioactivity in their glycerolipids was the same. In 5 rabbits, a biologically labelled triglyceride-rich VLDL1 subfraction preparation was administered and the specific activity of triglyceride was determined in all 3 subfractions in serial samples. A precursor--product relationship between VLDL1 TG and VLDL TG in other subfractions was not observed. In another set of experiments the disappearance rates of VLDL TG from subfractions were determined in recipient rabbits. The half-lives were: VLDL1 TG = 9.5 +/- 1.3 min, VLDL2 TG : 16.0 +/- 1.3 min, VLDL3 TG: 26.9 +/- 1.3 min. It is concluded that triglyceride removal from a VLDL subfraction varies inversely with its triglyceride content. A role for partial VLDL lipolysis in this metabolic heterogeneity was not established.", "contents": "Triglyceride removal from very low density lipoproteins in vivo as a function of their triglyceride content. Rabbit very low density lipoproteins (VLDL) were fractionated in 3 subfractions differing in density and triglyceride (TG) content. The fraction of total weight represented by triglycerides was: VLDL1 TG = 71%, VLDL2 TG = 62%, VLDL3 TG = 55%. No other difference in composition was observed. After intravenous administration of radioglycerol all subfractions were labelled and the distribution of radioactivity in their glycerolipids was the same. In 5 rabbits, a biologically labelled triglyceride-rich VLDL1 subfraction preparation was administered and the specific activity of triglyceride was determined in all 3 subfractions in serial samples. A precursor--product relationship between VLDL1 TG and VLDL TG in other subfractions was not observed. In another set of experiments the disappearance rates of VLDL TG from subfractions were determined in recipient rabbits. The half-lives were: VLDL1 TG = 9.5 +/- 1.3 min, VLDL2 TG : 16.0 +/- 1.3 min, VLDL3 TG: 26.9 +/- 1.3 min. It is concluded that triglyceride removal from a VLDL subfraction varies inversely with its triglyceride content. A role for partial VLDL lipolysis in this metabolic heterogeneity was not established."}
{"id": "PMID:223584", "title": "Cholesteryl ester distribution in lecithin bilayer membranes.", "content": "The saturated cholesteryl ester, cholesteryl 16-doxylstearate, is shown to incorporate into hydrated egg yolk lecithin multilayers in two distinct forms as visualized by electron spin resonance (ESR) spectroscopy. At concentrations less than 1 mole%, the ester is uniformly distributed in the membrane while at higher concentrations, patches of solid ester are formed.", "contents": "Cholesteryl ester distribution in lecithin bilayer membranes. The saturated cholesteryl ester, cholesteryl 16-doxylstearate, is shown to incorporate into hydrated egg yolk lecithin multilayers in two distinct forms as visualized by electron spin resonance (ESR) spectroscopy. At concentrations less than 1 mole%, the ester is uniformly distributed in the membrane while at higher concentrations, patches of solid ester are formed."}
{"id": "PMID:223585", "title": "LDL-induced cytotoxicity and its inhibition by HDL in human vascular smooth muscle and endothelial cells in culture.", "content": "Human aortic medial smooth muscle cells (SMC) and umbilical vein endothelial cells (EC) in culture were exposed to various concentrations of plasma low density (LDL) and high density (HDL) lipoproteins prepared from normolipemic donors in order to assess their effects on cell growth. So that the effects of each lipoprotein could be evaluated separately and in combination, lipoproteins were added to culture medium containing lipoprotein deficient serum (LPDS, d greater than 1.25 g/ml at a protein concentration of 4.5 mg/ml of medium). The addition of LDL at cholesterol concentrations of 160 microgram/ml of culture medium, resulted in significant reductions in both the number of SMC and EC cells per dish within 3 days of exposure (P less than 0.001, SMC; P less than 0.01, EC), when compared with LPDS controls and the starting cell numbers. This cytotoxic phenomenon was dose-related, and only at LDL cholesterol concentrations equal to or below 50 microgram/ml were no marked changes observed. In contrast, HDL at all concentrations tested produced no such deleterious effects. Autoradiographic assessment of DNA synthesis confirmed these findings. After 48 h of continuous exposure to tritiated thymidine, labeling indexes reached much lower plateaus in the LDL-treated groups.", "contents": "LDL-induced cytotoxicity and its inhibition by HDL in human vascular smooth muscle and endothelial cells in culture. Human aortic medial smooth muscle cells (SMC) and umbilical vein endothelial cells (EC) in culture were exposed to various concentrations of plasma low density (LDL) and high density (HDL) lipoproteins prepared from normolipemic donors in order to assess their effects on cell growth. So that the effects of each lipoprotein could be evaluated separately and in combination, lipoproteins were added to culture medium containing lipoprotein deficient serum (LPDS, d greater than 1.25 g/ml at a protein concentration of 4.5 mg/ml of medium). The addition of LDL at cholesterol concentrations of 160 microgram/ml of culture medium, resulted in significant reductions in both the number of SMC and EC cells per dish within 3 days of exposure (P less than 0.001, SMC; P less than 0.01, EC), when compared with LPDS controls and the starting cell numbers. This cytotoxic phenomenon was dose-related, and only at LDL cholesterol concentrations equal to or below 50 microgram/ml were no marked changes observed. In contrast, HDL at all concentrations tested produced no such deleterious effects. Autoradiographic assessment of DNA synthesis confirmed these findings. After 48 h of continuous exposure to tritiated thymidine, labeling indexes reached much lower plateaus in the LDL-treated groups."}
{"id": "PMID:223586", "title": "Correlation in the human aorta of APO B fractions with tissue cholesterol and collagen content.", "content": "The amounts of buffer- and Triton-extracted apo B (LDL-protein), as well as the sum of these two fractions, were correlated with the total tissue cholesterol and hydroxyproline content (as a measure of collagen) in grossly normal intima, fatty streaks, and fibrous plaques of human aortas obtained at autopsy. Quantitative values of buffer- and Triton-extracted apo B were obtained by sequentially extracting homogenates of aortic intima with an aqueous buffer and one containing Triton X-100, and measuring the apo B content in each extract by an electroimmunoassay relative to plasma LDL or Triton-treated LDL. Significant positive correlations were obtained between the following: tissue cholesterol and both buffer-extracted and total-extracted apo B in grossly normal intima; tissue cholesterol and Triton-extracted apo B in microdissected fibrotic caps and cores of fibrous plaques, as well as in whole plaques. A positive correlation was also obtained between tissue cholesterol and total-extracted apo B in the necrotic core. A significant negative correlation was found between Triton-extracted apo B and collagen in whole plaques. The calculated mean percent of total tissue cholesterol in the different aortic regions that could be present as part of an intact LDL particle were: 100% in grossly normal intima, 16% in fatty streaks, and 11% in fibrous plaques. The positive correlation between Triton-extracted apo B and cholesterol in plaques suggests one or both of the following: the extracellular pool of cholesterol or some material increasing concurrently with cholesterol interacts with apo B or another part of the LDL particle; or the apo B containing lipoprotein is trapped in the hydrophobic environment of extracellular lipid. Both possibilities would render the particle less soluble in aqueous buffers. The negative correlation between Triton-extracted apo B and tissue collagen and the lack of a significant correlation between buffer-extracted apo B and collagen content suggests that collagen is probably not responsible for apo B retention in the aortic intima.", "contents": "Correlation in the human aorta of APO B fractions with tissue cholesterol and collagen content. The amounts of buffer- and Triton-extracted apo B (LDL-protein), as well as the sum of these two fractions, were correlated with the total tissue cholesterol and hydroxyproline content (as a measure of collagen) in grossly normal intima, fatty streaks, and fibrous plaques of human aortas obtained at autopsy. Quantitative values of buffer- and Triton-extracted apo B were obtained by sequentially extracting homogenates of aortic intima with an aqueous buffer and one containing Triton X-100, and measuring the apo B content in each extract by an electroimmunoassay relative to plasma LDL or Triton-treated LDL. Significant positive correlations were obtained between the following: tissue cholesterol and both buffer-extracted and total-extracted apo B in grossly normal intima; tissue cholesterol and Triton-extracted apo B in microdissected fibrotic caps and cores of fibrous plaques, as well as in whole plaques. A positive correlation was also obtained between tissue cholesterol and total-extracted apo B in the necrotic core. A significant negative correlation was found between Triton-extracted apo B and collagen in whole plaques. The calculated mean percent of total tissue cholesterol in the different aortic regions that could be present as part of an intact LDL particle were: 100% in grossly normal intima, 16% in fatty streaks, and 11% in fibrous plaques. The positive correlation between Triton-extracted apo B and cholesterol in plaques suggests one or both of the following: the extracellular pool of cholesterol or some material increasing concurrently with cholesterol interacts with apo B or another part of the LDL particle; or the apo B containing lipoprotein is trapped in the hydrophobic environment of extracellular lipid. Both possibilities would render the particle less soluble in aqueous buffers. The negative correlation between Triton-extracted apo B and tissue collagen and the lack of a significant correlation between buffer-extracted apo B and collagen content suggests that collagen is probably not responsible for apo B retention in the aortic intima."}
{"id": "PMID:223587", "title": "High density lipoprotein cholesterol in male relatives of patients with coronary heart disease.", "content": "To study factors that play a role in the familial occurrence of coronary heart disease, very low density lipoprotein (VLDL) triglycerides, low density lipoprotein (LDL) cholesterol and high density lipoprotein (HDL) cholesterol were measured after preparative ultracentrifugation in first degree male relatives of coronary patients and in control subjects. The HDL cholesterol concentration was significantly lower in relatives of 20--71 years old than in controls. No increase of serum and LDL cholesterol was found. A low level of HDL cholesterol was observed even in the younger relatives who are less likely to have cardiovascualr disease. In older relatives low HDL cholesterol was found in the presence or absence of clinical evidence of coronary artery disease. The HDL-cholesterol concentration was inversely related to the VLDL triglycerides both in relatives and controls, but the regression lines were different ((P less than 0.001) for the relative (y = --0.166x + 0.43) and for the controls (y = 0.191x + 0.49). A low HDL cholesterol level appears to be a marker of relatives of coronary patients.", "contents": "High density lipoprotein cholesterol in male relatives of patients with coronary heart disease. To study factors that play a role in the familial occurrence of coronary heart disease, very low density lipoprotein (VLDL) triglycerides, low density lipoprotein (LDL) cholesterol and high density lipoprotein (HDL) cholesterol were measured after preparative ultracentrifugation in first degree male relatives of coronary patients and in control subjects. The HDL cholesterol concentration was significantly lower in relatives of 20--71 years old than in controls. No increase of serum and LDL cholesterol was found. A low level of HDL cholesterol was observed even in the younger relatives who are less likely to have cardiovascualr disease. In older relatives low HDL cholesterol was found in the presence or absence of clinical evidence of coronary artery disease. The HDL-cholesterol concentration was inversely related to the VLDL triglycerides both in relatives and controls, but the regression lines were different ((P less than 0.001) for the relative (y = --0.166x + 0.43) and for the controls (y = 0.191x + 0.49). A low HDL cholesterol level appears to be a marker of relatives of coronary patients."}
{"id": "PMID:223588", "title": "Modulation by sodium ascorbate of the effect of chloroquine on low density lipoprotein retention and degradation in cultured human skin fibroblasts.", "content": "Human skin fibroblasts in culture were incubated for 48 h with 125I-labelled low density lipoprotein and chloroquine in the presence and absence of sodium ascorbate. Pretreatment of the cells for 3 days with sodium ascorbate and addition of the vitamin during incubation resulted in a decrease in cellular retention and an increase in degradation of the labelled low density lipoprotein. Similar results were obtained when the cells were pretreated for 3 days but the vitamin was not added during the final 48 h of incubation. Pretreatment of the cells with dithiothreitol, butylated hydroxy-toluene, beta-mercaptoethanol and D-alpha-tocopherol had a similar effect to that of ascorbate, i.e. reduction in low density lipoprotein retention and increase in degradation. Neither ascorbate nor the other reducing agents affected low density lipoprotein catabolism in control cells not treated with chloroquine. Sodium ascorbate pretreatment resulted also in a slight but significant alleviation of the chloroquine-induced inhibition of hydrolysis of cholesterol linoleate. It is proposed that sodium ascorbate by virtue of its reducing properties provides some protection to the intralysosomal hydrolases against the inhibitory action of chloroquine. If cholesterol accumulation in human and experimental atheroma is caused by partial inhibition of lysosomal enzymes, sodium ascorbate could play a role in the alleviation of such an inhibition.", "contents": "Modulation by sodium ascorbate of the effect of chloroquine on low density lipoprotein retention and degradation in cultured human skin fibroblasts. Human skin fibroblasts in culture were incubated for 48 h with 125I-labelled low density lipoprotein and chloroquine in the presence and absence of sodium ascorbate. Pretreatment of the cells for 3 days with sodium ascorbate and addition of the vitamin during incubation resulted in a decrease in cellular retention and an increase in degradation of the labelled low density lipoprotein. Similar results were obtained when the cells were pretreated for 3 days but the vitamin was not added during the final 48 h of incubation. Pretreatment of the cells with dithiothreitol, butylated hydroxy-toluene, beta-mercaptoethanol and D-alpha-tocopherol had a similar effect to that of ascorbate, i.e. reduction in low density lipoprotein retention and increase in degradation. Neither ascorbate nor the other reducing agents affected low density lipoprotein catabolism in control cells not treated with chloroquine. Sodium ascorbate pretreatment resulted also in a slight but significant alleviation of the chloroquine-induced inhibition of hydrolysis of cholesterol linoleate. It is proposed that sodium ascorbate by virtue of its reducing properties provides some protection to the intralysosomal hydrolases against the inhibitory action of chloroquine. If cholesterol accumulation in human and experimental atheroma is caused by partial inhibition of lysosomal enzymes, sodium ascorbate could play a role in the alleviation of such an inhibition."}
{"id": "PMID:223589", "title": "Effects of caloric restriction on lipid metabolism in man: changes of tissue lipoprotein lipase activities and of serum lipoproteins.", "content": "Heparin-releasable lipoprotein lipase (LPL) activity was measured in biopsy samples of adipose tissue and skeletal muscle of 8 normal healthy females, first during an isocaloric diet and then after 2 and 7 days on a 400-kcal diet. In adipose tissue the LPL activity expressed per tissue weight fell to 38% and to 22% of the initial level after 2 and 7 days' caloric restriction, respectively. In skeletal muscle the LPL activity rose slightly after two days (+24%) but decreased to 49% of the initial value after seven days on diet. The estimated total body LPL activity decreased to 50% and to 20% of the baseline value after 2 and 7 days, respectively, but the relative contribution of skeletal muscle to the total LPL increased from 10 to 30%. The triglyceride and VLDL triglyceride concentrations were not significantly changed during the low calorie diet but the LDL triglyceride increased and the HDL cholesterol decreased significantly (P less than 0.01). It is concluded that substantial restriction of calorie intake results in a decrease of over-all triglyceride removal capacity but in an increase of the fraction removed by skeletal muscle. The decrease of HDL cholesterol is probably a consequence of the low turnover of exogenous and endogenous triglyceride-rich lipoproteins.", "contents": "Effects of caloric restriction on lipid metabolism in man: changes of tissue lipoprotein lipase activities and of serum lipoproteins. Heparin-releasable lipoprotein lipase (LPL) activity was measured in biopsy samples of adipose tissue and skeletal muscle of 8 normal healthy females, first during an isocaloric diet and then after 2 and 7 days on a 400-kcal diet. In adipose tissue the LPL activity expressed per tissue weight fell to 38% and to 22% of the initial level after 2 and 7 days' caloric restriction, respectively. In skeletal muscle the LPL activity rose slightly after two days (+24%) but decreased to 49% of the initial value after seven days on diet. The estimated total body LPL activity decreased to 50% and to 20% of the baseline value after 2 and 7 days, respectively, but the relative contribution of skeletal muscle to the total LPL increased from 10 to 30%. The triglyceride and VLDL triglyceride concentrations were not significantly changed during the low calorie diet but the LDL triglyceride increased and the HDL cholesterol decreased significantly (P less than 0.01). It is concluded that substantial restriction of calorie intake results in a decrease of over-all triglyceride removal capacity but in an increase of the fraction removed by skeletal muscle. The decrease of HDL cholesterol is probably a consequence of the low turnover of exogenous and endogenous triglyceride-rich lipoproteins."}
{"id": "PMID:223590", "title": "Hypolipidemic effects in dogs of ML-236B, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase.", "content": "ML-236B, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, significantly reduced both serum cholesterol and phospholipid levels in dogs, when used at a dosage higher than 10 mg/kg per day. Triglyceride levels were not consistently changed, but beta- and pre-beta-lipoproteins were preferentially reduced. Serum cholesterol levels were reduced by 44--45% at the higher dosage of 100--400 mg/kg per day (for 5 weeks) but ML-236B caused no significant changes in the cholesterol content of the liver and aorta and in the activities of serum GOT, GPT, CPK and lecithin : cholesterol acyltransferase. Fecal excretion of neutral sterols was unaffected but that of bile acids was markedly elevated by the drug. Under these conditions, hepatic cholesterol 7alpha-hydroxylase, the rate-limiting enzyme in bile acid biosynthesis, showed no detectable changes.", "contents": "Hypolipidemic effects in dogs of ML-236B, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. ML-236B, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, significantly reduced both serum cholesterol and phospholipid levels in dogs, when used at a dosage higher than 10 mg/kg per day. Triglyceride levels were not consistently changed, but beta- and pre-beta-lipoproteins were preferentially reduced. Serum cholesterol levels were reduced by 44--45% at the higher dosage of 100--400 mg/kg per day (for 5 weeks) but ML-236B caused no significant changes in the cholesterol content of the liver and aorta and in the activities of serum GOT, GPT, CPK and lecithin : cholesterol acyltransferase. Fecal excretion of neutral sterols was unaffected but that of bile acids was markedly elevated by the drug. Under these conditions, hepatic cholesterol 7alpha-hydroxylase, the rate-limiting enzyme in bile acid biosynthesis, showed no detectable changes."}
{"id": "PMID:223591", "title": "Metabolism of apolipoprotein B-containing lipoproteins in familial hypercholesterolaemia: effects of plasma exchange.", "content": "The turnover of apolipoprotein B (apo B) in very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and low density lipoprotein (LDL) was investigated in 2 homozygous and 3 heterozygous patients with familial hypercholesterolaemia. The effects of a marked reduction in plasma LDL concentration, brought about by plasma exchange, upon apo B turnover were studied in 4 patients. Specific activity-time curves for the the plasma apo B after intravenous radioactive VLDL before plasma exchange indicated that in the heterozygotes all IDL-apo B was derived from VLDL and all LDL-apo B was derived from IDL, but the curves from the homozygotes showed that a significant fraction of the LDL in the plasma was not derived from IDL. Plasma exchange did not increase the rates of synthesis of LDL-apo B or VLDL-apo B and had no significant effect on the precursor--product relationship between IDL-apo B and LDL-apo B in heterozygous or homozygous patients. These findings provide no support for the hypothesis that apo B synthesis is controlled by the plasma LDL.", "contents": "Metabolism of apolipoprotein B-containing lipoproteins in familial hypercholesterolaemia: effects of plasma exchange. The turnover of apolipoprotein B (apo B) in very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and low density lipoprotein (LDL) was investigated in 2 homozygous and 3 heterozygous patients with familial hypercholesterolaemia. The effects of a marked reduction in plasma LDL concentration, brought about by plasma exchange, upon apo B turnover were studied in 4 patients. Specific activity-time curves for the the plasma apo B after intravenous radioactive VLDL before plasma exchange indicated that in the heterozygotes all IDL-apo B was derived from VLDL and all LDL-apo B was derived from IDL, but the curves from the homozygotes showed that a significant fraction of the LDL in the plasma was not derived from IDL. Plasma exchange did not increase the rates of synthesis of LDL-apo B or VLDL-apo B and had no significant effect on the precursor--product relationship between IDL-apo B and LDL-apo B in heterozygous or homozygous patients. These findings provide no support for the hypothesis that apo B synthesis is controlled by the plasma LDL."}
{"id": "PMID:223592", "title": "High and low density lipoprotein cholesterol in myocardial and cerebral infarction.", "content": "High density lipoprotein (HDL) and low density lipoprotein (LdL) cholesterol levels were measured in fasting blood samples from 950 healthy subjects and 188 aged patients by a new simple method. The HDL-cholesterol levels and HDL/LDL-cholesterol ratios are significantly higher in females than in males. In the healthy subjects, there are slight decreases in the levels of HDL-cholesterol and HDL/LDL-cholesterol ratio with aging in both sexes. The patients with myocardial infarction had significantly lower HDL-cholesterol levels and HDL/LDL-cholesterol ratios as compared to those of the group without infarction. On the contrary, no differences in total lipoprotein cholesterol levels were observed in the patients with cerebral infarction. The results, obtained in respect of electrocardiographic findings after the isoproterenol stress test, suggest that the HDL-cholesterol levels and HDL/LDL-cholesterol ratios may be related not only to the established myocardial infarction, but also to the presence of coronary atherosclerosis and stenosis.", "contents": "High and low density lipoprotein cholesterol in myocardial and cerebral infarction. High density lipoprotein (HDL) and low density lipoprotein (LdL) cholesterol levels were measured in fasting blood samples from 950 healthy subjects and 188 aged patients by a new simple method. The HDL-cholesterol levels and HDL/LDL-cholesterol ratios are significantly higher in females than in males. In the healthy subjects, there are slight decreases in the levels of HDL-cholesterol and HDL/LDL-cholesterol ratio with aging in both sexes. The patients with myocardial infarction had significantly lower HDL-cholesterol levels and HDL/LDL-cholesterol ratios as compared to those of the group without infarction. On the contrary, no differences in total lipoprotein cholesterol levels were observed in the patients with cerebral infarction. The results, obtained in respect of electrocardiographic findings after the isoproterenol stress test, suggest that the HDL-cholesterol levels and HDL/LDL-cholesterol ratios may be related not only to the established myocardial infarction, but also to the presence of coronary atherosclerosis and stenosis."}
{"id": "PMID:223597", "title": "Lecithin : cholesterol acyl transfer (LACT) and fatty acid composition of lecithin and cholesterol esters in young male myocardial infarction survivors.", "content": "Lecithin : cholesterol acyl transfer (LCAT) and relative fatty acid composition of serum lecithin and cholesterol esters were studied in 20 young male survivors of myocardial infarction (MI). Comparisons were made with controls matched for serum cholesterol. There was no difference in LCAT rate between MI patients and controls. The relative content of arachidonic acid in cholesterol esters was higher in MI patients. The fatty acid composition of lecithin and cholesterol esters suggests an equal transfer of linoleic and oleic acids from lecithin to cholesterol. Furthermore negative correlations were found between LCAT and linoleic acid content of lecithin (r = --0.43, P less than 0.01) and cholesterol esters (r = --0.45, P less than 0.01). This inverse relationship does not seem to be linked to substrate specificity, but rather to be mediated by influences in common on serum lipid content and turnover.", "contents": "Lecithin : cholesterol acyl transfer (LACT) and fatty acid composition of lecithin and cholesterol esters in young male myocardial infarction survivors. Lecithin : cholesterol acyl transfer (LCAT) and relative fatty acid composition of serum lecithin and cholesterol esters were studied in 20 young male survivors of myocardial infarction (MI). Comparisons were made with controls matched for serum cholesterol. There was no difference in LCAT rate between MI patients and controls. The relative content of arachidonic acid in cholesterol esters was higher in MI patients. The fatty acid composition of lecithin and cholesterol esters suggests an equal transfer of linoleic and oleic acids from lecithin to cholesterol. Furthermore negative correlations were found between LCAT and linoleic acid content of lecithin (r = --0.43, P less than 0.01) and cholesterol esters (r = --0.45, P less than 0.01). This inverse relationship does not seem to be linked to substrate specificity, but rather to be mediated by influences in common on serum lipid content and turnover."}
{"id": "PMID:223598", "title": "Beta- and pre-beta-lipoproteins in coronary disease and hyperlipoproteinaemia.", "content": "A very high percentage of male patients with proven coronary disease and/or raised lipid levels had a pre-beta-hyperlipoproteinaemia (class P [6] or Fredrickson [3] type IV) and relatively few had a beta-hyperlipoproteinaemia (class B or Fredrickson type IIA). Mixed hyperlipoproteinaemia was found in a large number of male patients but these again had predominantly raised triglyceride. More female patients over 40 years had beta-hyperlipoproteinaemia. Our retrospective study shows that raised triglyceride levels are more often found in patients with coronary disease than raised cholesterol levels.", "contents": "Beta- and pre-beta-lipoproteins in coronary disease and hyperlipoproteinaemia. A very high percentage of male patients with proven coronary disease and/or raised lipid levels had a pre-beta-hyperlipoproteinaemia (class P [6] or Fredrickson [3] type IV) and relatively few had a beta-hyperlipoproteinaemia (class B or Fredrickson type IIA). Mixed hyperlipoproteinaemia was found in a large number of male patients but these again had predominantly raised triglyceride. More female patients over 40 years had beta-hyperlipoproteinaemia. Our retrospective study shows that raised triglyceride levels are more often found in patients with coronary disease than raised cholesterol levels."}
{"id": "PMID:223600", "title": "Dietary fiber and cholesterol metabolism in rats fed a high cholesterol diet.", "content": "The effect of administering blackgram (Phaseolus mungo) fiber (isolated as neutral detergent residue) at the 30% dietary level has been studied with regard to lipid concentration in the tissues and that of biliary and fecal bile acids and sterols. Rats were fed a high fat-cholesterol diet and compared with those fed a cellulose diet. The results indicate that blackgram fiber significantly lowers cholesterol in both serum and aorta [11]. There was an increased concentration of biliary sterols and bile acids and increased fecal excretion of sterols and bile acids, each of these effects being significantly greater than those observed in the rats fed cellulose.", "contents": "Dietary fiber and cholesterol metabolism in rats fed a high cholesterol diet. The effect of administering blackgram (Phaseolus mungo) fiber (isolated as neutral detergent residue) at the 30% dietary level has been studied with regard to lipid concentration in the tissues and that of biliary and fecal bile acids and sterols. Rats were fed a high fat-cholesterol diet and compared with those fed a cellulose diet. The results indicate that blackgram fiber significantly lowers cholesterol in both serum and aorta [11]. There was an increased concentration of biliary sterols and bile acids and increased fecal excretion of sterols and bile acids, each of these effects being significantly greater than those observed in the rats fed cellulose."}
{"id": "PMID:223601", "title": "Long-term effect of the combination of calcium clofibrate and calcium carbonate on serum total cholesterol, triglyceride and high density lipoprotein--cholesterol concentrations in hyperlipoproteinaemia. A comparative study with clofibrate.", "content": "Thirty hyperlipidaemic patients (19 with type IIA, 4 with IIB and 7 with type IV hyperlipoproteinaemia) were subjected to therapy with calcium clofibrate and calcium carbonate (4C, 2 + 2 g/day for 6 months) and the effect was compared with clofibrate (1C, 2 g/day) which was given for 6 months as well, in a single-blind placebo-controlled study. 4C and 1C decreased total serum cholesterol levels especially in subgroups IIA and IIB. 4C was somewhat more effective than 1C in decreasing (VLDL + LDL)-cholesterol in subgroup IIA. The HDL-cholesterol concentrations and the ratio of HDL-cholesterol and total cholesterol increased during treatment with both 1C and 4C. The HDL-cholesterol increase (vs. placebo) was 18%. The concentrations of serum triglycerides decreased by 33% during both treatment periods and there was no significant difference between 1C and 4C.", "contents": "Long-term effect of the combination of calcium clofibrate and calcium carbonate on serum total cholesterol, triglyceride and high density lipoprotein--cholesterol concentrations in hyperlipoproteinaemia. A comparative study with clofibrate. Thirty hyperlipidaemic patients (19 with type IIA, 4 with IIB and 7 with type IV hyperlipoproteinaemia) were subjected to therapy with calcium clofibrate and calcium carbonate (4C, 2 + 2 g/day for 6 months) and the effect was compared with clofibrate (1C, 2 g/day) which was given for 6 months as well, in a single-blind placebo-controlled study. 4C and 1C decreased total serum cholesterol levels especially in subgroups IIA and IIB. 4C was somewhat more effective than 1C in decreasing (VLDL + LDL)-cholesterol in subgroup IIA. The HDL-cholesterol concentrations and the ratio of HDL-cholesterol and total cholesterol increased during treatment with both 1C and 4C. The HDL-cholesterol increase (vs. placebo) was 18%. The concentrations of serum triglycerides decreased by 33% during both treatment periods and there was no significant difference between 1C and 4C."}
{"id": "PMID:223602", "title": "Atherogenic diets and neutral-lipid organization in plasma low density lipoproteins.", "content": "The plasma low density lipoproteins (LDL) of rhesus monkeys fed 3 atherogenic diets exhibited thermal transitions at temperatures much higher (37--43 degrees C) than those observed in control animals or in normal humans (20--33 degrees C). The same differences were noted in the neutral lipids (cholesteryl esters and triglycerides) which were isolated from the respective lipoproteins. In particular, the difference in thermal properties between the normal and abnormal LDLs was attributable to subtle differences in their cholesteryl ester compositions (mainly an increase in the saturated and monounsaturated fatty acid moieties), with altered triglyceride contents playing only a minor role. Thus, at body temperature, the hyperlipidemia that follows the administration of atherogenic diets is associated with a high degree of order of the neutral lipids in the core of the LDL particle. This, in turn, may be related to the atherogenicity of the abnormal lipoprotein species.", "contents": "Atherogenic diets and neutral-lipid organization in plasma low density lipoproteins. The plasma low density lipoproteins (LDL) of rhesus monkeys fed 3 atherogenic diets exhibited thermal transitions at temperatures much higher (37--43 degrees C) than those observed in control animals or in normal humans (20--33 degrees C). The same differences were noted in the neutral lipids (cholesteryl esters and triglycerides) which were isolated from the respective lipoproteins. In particular, the difference in thermal properties between the normal and abnormal LDLs was attributable to subtle differences in their cholesteryl ester compositions (mainly an increase in the saturated and monounsaturated fatty acid moieties), with altered triglyceride contents playing only a minor role. Thus, at body temperature, the hyperlipidemia that follows the administration of atherogenic diets is associated with a high degree of order of the neutral lipids in the core of the LDL particle. This, in turn, may be related to the atherogenicity of the abnormal lipoprotein species."}
{"id": "PMID:223605", "title": "[Histological and electron microscopic study of the cerebral cortex of the progeny of neurosensitized rats].", "content": "The sensomotor brain cortex of 30-day ratlings born by preliminary neurosensitized females, was studied. The studies demonstrated retardation in the development of the brain cortex in the progeny. Electon microscopic examinations detected certain features in the structure of cellular organella, as well as membrane formations in the nuclei of the cortical neurons. These changes are considered as an expression of a lowered level of neuron functioning.", "contents": "[Histological and electron microscopic study of the cerebral cortex of the progeny of neurosensitized rats]. The sensomotor brain cortex of 30-day ratlings born by preliminary neurosensitized females, was studied. The studies demonstrated retardation in the development of the brain cortex in the progeny. Electon microscopic examinations detected certain features in the structure of cellular organella, as well as membrane formations in the nuclei of the cortical neurons. These changes are considered as an expression of a lowered level of neuron functioning."}
{"id": "PMID:223609", "title": "Heart proteins, in situ dissolution of myofibrillar actomyosin in bovine heart.", "content": "Immersion of small pieces of bovine heart into 0.2 M pyrophosphate, or 0.6 M KCl for 24 hours at +5 degrees results in the dissolution of actomyosin filaments in the tissue. Immersion into distilled water under the same conditions has no such effect.", "contents": "Heart proteins, in situ dissolution of myofibrillar actomyosin in bovine heart. Immersion of small pieces of bovine heart into 0.2 M pyrophosphate, or 0.6 M KCl for 24 hours at +5 degrees results in the dissolution of actomyosin filaments in the tissue. Immersion into distilled water under the same conditions has no such effect."}
{"id": "PMID:223610", "title": "Adaptation to hypertonicity and selection of cell hybrids.", "content": "The ability to survive in hypertonic media varies markedly among different cell strains. This property was exploited to set up a selection procedure to isolate cell hybrids, in cell fusion experiments. The results of a cross between two EUE sublines, with a differential sensitivity to hypertonicity, are discussed.", "contents": "Adaptation to hypertonicity and selection of cell hybrids. The ability to survive in hypertonic media varies markedly among different cell strains. This property was exploited to set up a selection procedure to isolate cell hybrids, in cell fusion experiments. The results of a cross between two EUE sublines, with a differential sensitivity to hypertonicity, are discussed."}
{"id": "PMID:223606", "title": "[Thrombocytopenic purpura of the young infant caused by perinatal infection by cytomegaloviruses].", "content": "Two cases of idiopathic trombocytopenic purpura, in infants 37 and 42 days old, and one case of atypical congenital cytomegaloviral disease are presented, the latter proved at necropsy. Cytomegalic inclusion cells are found in urine in both cases of purpura with hepatosplenomegaly and mononucleosis syndrome. In one of the cases, cytomegalovirus cultures are positive in urine and blood. The hemorrhagic syndrome is mild and recuperation is achieved in less than thirty days, without relapse. The use of corticosteroids is not recommended. With these two new cases, thirteen similar clinical observation of thrombocytopenic purpura in infants, six of them in 1977, are completed. Thus, a new entity is added to the growing list of clinical manifestations caused by human CMV infection.", "contents": "[Thrombocytopenic purpura of the young infant caused by perinatal infection by cytomegaloviruses]. Two cases of idiopathic trombocytopenic purpura, in infants 37 and 42 days old, and one case of atypical congenital cytomegaloviral disease are presented, the latter proved at necropsy. Cytomegalic inclusion cells are found in urine in both cases of purpura with hepatosplenomegaly and mononucleosis syndrome. In one of the cases, cytomegalovirus cultures are positive in urine and blood. The hemorrhagic syndrome is mild and recuperation is achieved in less than thirty days, without relapse. The use of corticosteroids is not recommended. With these two new cases, thirteen similar clinical observation of thrombocytopenic purpura in infants, six of them in 1977, are completed. Thus, a new entity is added to the growing list of clinical manifestations caused by human CMV infection."}
{"id": "PMID:223611", "title": "Studies on the cholesterol synthesis in the human adipose tissue. II. Mechanism of metabolic shifts and regulation of cholesterol through ascorbic acid.", "content": "Ratios of yields of cholesterol in different media with different metabolites (200 estimations) show that if the initial normal quantity in a system is X, glucose makes it 4X which is then reduced by the amino acids and ascorbic acid. Alanine, Serine, Threonine, Cysteine, Cystine and Lysine reduce it to 2X. Glycine, Valine, Leucine, Aspartic, Phenylalanine, Tyrosine, Tryptophan roughly increase it to 6X. Other amino acids are intermediate between the above sets. Balanced amino acids and fatty acids keep up the glucose value 4X but the individual amino acids behave as above. Ascorbic acid reduces the quantity of cholesterol everywhere from one third to one half bringing it back to normal X. Since it is not directly involved in the cholesterol synthesis, it must be acting through the pyridine nucleotides. The interesting feature is that the C/H ratio in the amino acids  corresponds to the yield of cholesterol with respect to glucose saline yield = 1. Mechanism of metabolic shifts has been discussed on the empirical basis as also on the basis of the change in ratios of NAD+ (NADP+) to NADH2 (NADPH2) through ascorbic acid.", "contents": "Studies on the cholesterol synthesis in the human adipose tissue. II. Mechanism of metabolic shifts and regulation of cholesterol through ascorbic acid. Ratios of yields of cholesterol in different media with different metabolites (200 estimations) show that if the initial normal quantity in a system is X, glucose makes it 4X which is then reduced by the amino acids and ascorbic acid. Alanine, Serine, Threonine, Cysteine, Cystine and Lysine reduce it to 2X. Glycine, Valine, Leucine, Aspartic, Phenylalanine, Tyrosine, Tryptophan roughly increase it to 6X. Other amino acids are intermediate between the above sets. Balanced amino acids and fatty acids keep up the glucose value 4X but the individual amino acids behave as above. Ascorbic acid reduces the quantity of cholesterol everywhere from one third to one half bringing it back to normal X. Since it is not directly involved in the cholesterol synthesis, it must be acting through the pyridine nucleotides. The interesting feature is that the C/H ratio in the amino acids  corresponds to the yield of cholesterol with respect to glucose saline yield = 1. Mechanism of metabolic shifts has been discussed on the empirical basis as also on the basis of the change in ratios of NAD+ (NADP+) to NADH2 (NADPH2) through ascorbic acid."}
{"id": "PMID:223612", "title": "Antibodies to Coxsackie B viruses in congestive cardiomyopathy.", "content": "Fifty patients with congestive cardiomyopathy have been studied for evidence of previous Coxsackie B virus infection and compared with age- and sex-matched controls who had been admitted to hospital for investigation of other cardiac diseases. High neutralisation titres (greater than or equal to 1024) to Coxsackie B viruses were more common among the controls. On subdividing the patients according to their length of symptomatic history before study, high titres were more common only in those with a short history (less than or equal to 1 year). High titres were more common when there had been a febrile illness at the onset of symptoms. Endomyocardial biopsies of 18 patients disclosed no evidence of myocarditis, or, in 12 cases, of viral involvement. Although the evidence remains circumstantial, these results support the theory that Coxsackie B viruses may cause congestive cardiomyopathy and encourage further research into the mechanisms of myocardial cell damage by these visuses.", "contents": "Antibodies to Coxsackie B viruses in congestive cardiomyopathy. Fifty patients with congestive cardiomyopathy have been studied for evidence of previous Coxsackie B virus infection and compared with age- and sex-matched controls who had been admitted to hospital for investigation of other cardiac diseases. High neutralisation titres (greater than or equal to 1024) to Coxsackie B viruses were more common among the controls. On subdividing the patients according to their length of symptomatic history before study, high titres were more common only in those with a short history (less than or equal to 1 year). High titres were more common when there had been a febrile illness at the onset of symptoms. Endomyocardial biopsies of 18 patients disclosed no evidence of myocarditis, or, in 12 cases, of viral involvement. Although the evidence remains circumstantial, these results support the theory that Coxsackie B viruses may cause congestive cardiomyopathy and encourage further research into the mechanisms of myocardial cell damage by these visuses."}
{"id": "PMID:223614", "title": "Orally active angiotensin-converting enzyme inhibitor (SO 14,225) as a treatment for essential hypertension.", "content": "1 Captopril (SQ14,225), an orally active inhibitor of angiotensin-converting enzyme, was administered to nine patients with essential hypertension. Plasma renin activity (PRA) was low in four, 'normal' in three and high in two patients. 2 In the hospital, captopril alone induced a significant drop in BP from 165 +/- 6/106 +/- 2 to 140 +/- 5/90 +/- 1 mmHb (P less than 0.001). PRA increased concomitantly (P less than 0.05), whereas plasma-converting enzyme activity (P less than 0.005) and plasma aldosterone (P less than 0.05) were reduced. 3 Six patients underwent chronic ambulatory therapy with captopril for a mean of 16 +/- 3 weeks. After discharge from the hospital, BP remained normalized but in five out of six patients this required additional diuretic therapy. 4 The results suggest that captopril alone or combined with diuretic therapy provides a new, efficient and well tolerated tool to treat patients with essential hypertension independently of their PRA level. It may turn out to be more effective in lowering BP than beta-adrenoceptor-blocking agents.", "contents": "Orally active angiotensin-converting enzyme inhibitor (SO 14,225) as a treatment for essential hypertension. 1 Captopril (SQ14,225), an orally active inhibitor of angiotensin-converting enzyme, was administered to nine patients with essential hypertension. Plasma renin activity (PRA) was low in four, 'normal' in three and high in two patients. 2 In the hospital, captopril alone induced a significant drop in BP from 165 +/- 6/106 +/- 2 to 140 +/- 5/90 +/- 1 mmHb (P less than 0.001). PRA increased concomitantly (P less than 0.05), whereas plasma-converting enzyme activity (P less than 0.005) and plasma aldosterone (P less than 0.05) were reduced. 3 Six patients underwent chronic ambulatory therapy with captopril for a mean of 16 +/- 3 weeks. After discharge from the hospital, BP remained normalized but in five out of six patients this required additional diuretic therapy. 4 The results suggest that captopril alone or combined with diuretic therapy provides a new, efficient and well tolerated tool to treat patients with essential hypertension independently of their PRA level. It may turn out to be more effective in lowering BP than beta-adrenoceptor-blocking agents."}
{"id": "PMID:223615", "title": "Inhibitors of the renin-angiotensin system in experimental hypertension, with a note on the measurement of angiotensin I, II and III during infusion of converting-enzyme inhibitor.", "content": "1 Prolonged infusion (11 h) of both saralasin and angiotensin-converting enzyme inhibitor (SQ20881) gradually lowered BP in two-kidney hypertensive rats to levels similar to that in normotensive rats infused with dextrose. 2 Saralasin did not lower BP in DOCA-salt hypertensive rats. 3 These observations support the notion that in chronic renal hypertension, angiotensin II may maintain hypertension by a slowly developing action. 4 Plasma angiotensin II in rats infused with SQ20881 was suppressed relative to renin, but was not eliminated. 5 Chromatography of angiotensin II extracts from dogs infused with converting enzyme inhibitor (SQ14,225) showed that the very high levels of angiotensin I achieved after treatment with SQ14,225 can lead to falsely high estimated angiotensin II levels as a result of angiotensin I cross-reacting with the angiotensin II assay.", "contents": "Inhibitors of the renin-angiotensin system in experimental hypertension, with a note on the measurement of angiotensin I, II and III during infusion of converting-enzyme inhibitor. 1 Prolonged infusion (11 h) of both saralasin and angiotensin-converting enzyme inhibitor (SQ20881) gradually lowered BP in two-kidney hypertensive rats to levels similar to that in normotensive rats infused with dextrose. 2 Saralasin did not lower BP in DOCA-salt hypertensive rats. 3 These observations support the notion that in chronic renal hypertension, angiotensin II may maintain hypertension by a slowly developing action. 4 Plasma angiotensin II in rats infused with SQ20881 was suppressed relative to renin, but was not eliminated. 5 Chromatography of angiotensin II extracts from dogs infused with converting enzyme inhibitor (SQ14,225) showed that the very high levels of angiotensin I achieved after treatment with SQ14,225 can lead to falsely high estimated angiotensin II levels as a result of angiotensin I cross-reacting with the angiotensin II assay."}
{"id": "PMID:223616", "title": "Animal and molecular pharmacology of mixed agonist-antagonist analgesic drugs.", "content": "1 The pharmacology of analgesic drugs with mixed agonist-antagonist action is reviewed in the light of the theory of drug action at single and multiple receptors. 2 Evidence for a heterogeneous population of opiate receptors in mammalian brain and in isolated tissue preparations is discussed. 3 The unusual pharmacological and pharmacokinetic profiles of the oripavine derivative buprenorphine are discussed in relation to the action of the drug at a molecular level.", "contents": "Animal and molecular pharmacology of mixed agonist-antagonist analgesic drugs. 1 The pharmacology of analgesic drugs with mixed agonist-antagonist action is reviewed in the light of the theory of drug action at single and multiple receptors. 2 Evidence for a heterogeneous population of opiate receptors in mammalian brain and in isolated tissue preparations is discussed. 3 The unusual pharmacological and pharmacokinetic profiles of the oripavine derivative buprenorphine are discussed in relation to the action of the drug at a molecular level."}
{"id": "PMID:223618", "title": "Effect of endogenous and exogenous prostaglandin E on Friend erythroleukaemia cell growth and differentiation.", "content": "The effect of exogenous and endogenous prostaglandins on the patterns of growth and differentiation of Friend erythroleukaemia cells (FLC) were studied. During the differentiation process, DMSO stimulated PGE synthesis by an average of 95%. The addition of a long-acting synthetic analogue of PGE2,16,16-dimethyl-PGE2-methyl ester (di-M-PGE2) to the culture medium only slightly and temporarily slowed cell growth, with no appreciable induction of differentiation. However, in the presence of DMSO, the same concentration of di-M-PGE2 produced 73% inhibition of cell growth and accelerated and potently stimulated haemoglobin production. The action of both di-M-PGE2 and DMSO on cell proliferation was dependent upon the state of cell growth at the time of the administration of these compounds. FLC cultures treated with DMSO + di-M-PGE2 produced considerable amounts of haemoglobin before even one duplication cycle was completed. Both DMSO and di-M-PGE2 stimulated endogenous PGE biosynthesis, and the biosynthetic effect of these compounds was synergistic. Inhibition of endogenous prostaglandin synthesis by indomethacin completely abolished the effects produced by DMSO + di-M-PGE2 on the growth, and substantially reduced the stimulated differentiation of FLC. These data suggest that an endogenously synthesized prostaglandin plays a significant role in both the inhibition of replication and in the stimulation of differentiation induced by DMSO and di-M-PGE2 in Friend erythroleukaemia cells.", "contents": "Effect of endogenous and exogenous prostaglandin E on Friend erythroleukaemia cell growth and differentiation. The effect of exogenous and endogenous prostaglandins on the patterns of growth and differentiation of Friend erythroleukaemia cells (FLC) were studied. During the differentiation process, DMSO stimulated PGE synthesis by an average of 95%. The addition of a long-acting synthetic analogue of PGE2,16,16-dimethyl-PGE2-methyl ester (di-M-PGE2) to the culture medium only slightly and temporarily slowed cell growth, with no appreciable induction of differentiation. However, in the presence of DMSO, the same concentration of di-M-PGE2 produced 73% inhibition of cell growth and accelerated and potently stimulated haemoglobin production. The action of both di-M-PGE2 and DMSO on cell proliferation was dependent upon the state of cell growth at the time of the administration of these compounds. FLC cultures treated with DMSO + di-M-PGE2 produced considerable amounts of haemoglobin before even one duplication cycle was completed. Both DMSO and di-M-PGE2 stimulated endogenous PGE biosynthesis, and the biosynthetic effect of these compounds was synergistic. Inhibition of endogenous prostaglandin synthesis by indomethacin completely abolished the effects produced by DMSO + di-M-PGE2 on the growth, and substantially reduced the stimulated differentiation of FLC. These data suggest that an endogenously synthesized prostaglandin plays a significant role in both the inhibition of replication and in the stimulation of differentiation induced by DMSO and di-M-PGE2 in Friend erythroleukaemia cells."}
{"id": "PMID:223619", "title": "Paramagnetic changes in cancer: DMBA-induced tumours studied in non-lyophilized and lyophilized tissues.", "content": "Electron spin resonance (ESR) studies were made on frozen samples of 7,12 dimethylbenzanthracene (DMBA)-induced rat breast tumours both before and after lyophilization. The primary purpose of these studies was to determine the relationship between ESR spectra under these two conditions and thereby hopefully resolve an apparent conflict as to the experimental findings and clinical implications of these findings. In contrast to the other system (Walker 256 carcinosarcoma) which we studied by a similar method, in the DMBA-induced tumours we found a close parallel between the ESR spectra before and after lyophilization. In both cases free-radical levels were elevated about two-fold in all tumours and showed little dependence on the age of the tumour. Studies of blood and liver before the development of tumours showed no change in free radicals levels in either nonlyophilized or lyophilized samples. In animals with tumours, the level of free radicals in the liver increased approximately 17%. Manganese (2+) levels were increased in breast tumours but the changes did not closely follow those of free radicals and were much more variable in the lyophilized samples. We conclude that: (1) there seems to be no general relationship between ESR spectra of tumours before and after lyophilization; (2) there appears to be no general pattern of ESR changes in lyophilized samples of tumours.", "contents": "Paramagnetic changes in cancer: DMBA-induced tumours studied in non-lyophilized and lyophilized tissues. Electron spin resonance (ESR) studies were made on frozen samples of 7,12 dimethylbenzanthracene (DMBA)-induced rat breast tumours both before and after lyophilization. The primary purpose of these studies was to determine the relationship between ESR spectra under these two conditions and thereby hopefully resolve an apparent conflict as to the experimental findings and clinical implications of these findings. In contrast to the other system (Walker 256 carcinosarcoma) which we studied by a similar method, in the DMBA-induced tumours we found a close parallel between the ESR spectra before and after lyophilization. In both cases free-radical levels were elevated about two-fold in all tumours and showed little dependence on the age of the tumour. Studies of blood and liver before the development of tumours showed no change in free radicals levels in either nonlyophilized or lyophilized samples. In animals with tumours, the level of free radicals in the liver increased approximately 17%. Manganese (2+) levels were increased in breast tumours but the changes did not closely follow those of free radicals and were much more variable in the lyophilized samples. We conclude that: (1) there seems to be no general relationship between ESR spectra of tumours before and after lyophilization; (2) there appears to be no general pattern of ESR changes in lyophilized samples of tumours."}
{"id": "PMID:223620", "title": "Xanthomatosis and other clinical findings in patients with elevated levels of very low density lipoproteins.", "content": "Forty-six patients with xanthomatosis and elevated very low density lipoproteins (VLDL) levels (in different types of hyperlipoproteinaemia) were classified on the basis of the WHO criteria and the cholesterol/triglyceride ratio in VLDL. A large majority (31/46) of the patients referred to the Department of Dermatology could be classified as hyperlipoproteinaemia type III, only 8/46 as type IIB and 7/46 as type IV/V. This distinction seems to be relevant as the xanthomatous lesions differed distinctly between these three types of hyperlipoproteinaemia. Xanthochromia striata palmaris was present in 29/31 cases of hyperlipoproteinaemia type III and was not found in type IV/V patients, who had distinctive papuloeruptive xanthomas. During a follow-up in 35/46 patients all xanthomas disappeared within 2 years except the xanthelasma palpebrarum and tendinous xanthomas. All type IV/V patients (7/7) but only one type III patient (1/31) had abnormal glucose tolerance. Only 2/18 type III patients less than 45 years showed claudication and none of the young type III patients had angina pectoris. In contrast, all four type IIB patients less than 45 years had clinical signs of atherosclerosis. However, angina pectoris and/or claudication were present in 5/13 type III patients over 45 years old. The mean serum cholesterol level was equally elevated in both groups but the cholesterol was mainly present in VLDL in type III and in low density lipoproteins (LDL) in type IIB. In 9/31 type III patients the LDL level was also elevated but was easily normalized by a diet low in carbohydrate, whereas the elevated LDL level in type IIB was therapy-resistant. The recognition of xanthomatous lesions, specifically xanthochromia striata palmaris, as an early sign of type III hyperlipoproteinaemia, can lead to the early diagnosis and successful treatment of these patients, and thus possibly prevent the development of premature atherosclerosis.", "contents": "Xanthomatosis and other clinical findings in patients with elevated levels of very low density lipoproteins. Forty-six patients with xanthomatosis and elevated very low density lipoproteins (VLDL) levels (in different types of hyperlipoproteinaemia) were classified on the basis of the WHO criteria and the cholesterol/triglyceride ratio in VLDL. A large majority (31/46) of the patients referred to the Department of Dermatology could be classified as hyperlipoproteinaemia type III, only 8/46 as type IIB and 7/46 as type IV/V. This distinction seems to be relevant as the xanthomatous lesions differed distinctly between these three types of hyperlipoproteinaemia. Xanthochromia striata palmaris was present in 29/31 cases of hyperlipoproteinaemia type III and was not found in type IV/V patients, who had distinctive papuloeruptive xanthomas. During a follow-up in 35/46 patients all xanthomas disappeared within 2 years except the xanthelasma palpebrarum and tendinous xanthomas. All type IV/V patients (7/7) but only one type III patient (1/31) had abnormal glucose tolerance. Only 2/18 type III patients less than 45 years showed claudication and none of the young type III patients had angina pectoris. In contrast, all four type IIB patients less than 45 years had clinical signs of atherosclerosis. However, angina pectoris and/or claudication were present in 5/13 type III patients over 45 years old. The mean serum cholesterol level was equally elevated in both groups but the cholesterol was mainly present in VLDL in type III and in low density lipoproteins (LDL) in type IIB. In 9/31 type III patients the LDL level was also elevated but was easily normalized by a diet low in carbohydrate, whereas the elevated LDL level in type IIB was therapy-resistant. The recognition of xanthomatous lesions, specifically xanthochromia striata palmaris, as an early sign of type III hyperlipoproteinaemia, can lead to the early diagnosis and successful treatment of these patients, and thus possibly prevent the development of premature atherosclerosis."}
{"id": "PMID:223622", "title": "Conduction velocity in the peripheral nerves of rats with chronic carbon disulphide neuropathy.", "content": "Effects of carbon disulphide (CS2) on conduction velocity in sciatic and tibial nerve were investigated in rats exposed to CS2 vapour at concentrations of 0.9 mg/l or 1.6 mg/l of air for periods of 1.5, 3, 6, 9 and 12 months. The conduction velocity was measured on the day following each exposure period, and again, three and six months after the last day of exposure. The majority of exposed rats showed a reduction in conduction velocity on the day after exposure: the extent of this reduction was dependent on the CS2 concentration and the duration of exposure. Exposure for 1.5 months to 1.6 mg CS2/l produced temporary and fully reversible impairment of conduction velocity. Increased exposure to CS2 (3,6 or 9 months at 1.6 mg/l; 6 or 12 months at 0.9 mg/l CS2 in air) caused a reduction in velocity which was only partially reversible.", "contents": "Conduction velocity in the peripheral nerves of rats with chronic carbon disulphide neuropathy. Effects of carbon disulphide (CS2) on conduction velocity in sciatic and tibial nerve were investigated in rats exposed to CS2 vapour at concentrations of 0.9 mg/l or 1.6 mg/l of air for periods of 1.5, 3, 6, 9 and 12 months. The conduction velocity was measured on the day following each exposure period, and again, three and six months after the last day of exposure. The majority of exposed rats showed a reduction in conduction velocity on the day after exposure: the extent of this reduction was dependent on the CS2 concentration and the duration of exposure. Exposure for 1.5 months to 1.6 mg CS2/l produced temporary and fully reversible impairment of conduction velocity. Increased exposure to CS2 (3,6 or 9 months at 1.6 mg/l; 6 or 12 months at 0.9 mg/l CS2 in air) caused a reduction in velocity which was only partially reversible."}
{"id": "PMID:223623", "title": "Discrepancies in the histological diagnosis of hydatidiform mole.", "content": "Sections of tissue from 256 patients on which a histological diagnosis of hydatidiform mole had been made were reviewed by a visiting pathologist. There was agreement between the reporting pathologists and the visiting pathologist in only 55.1 per cent of cases, a less severe diagnosis was made by the visiting pathologist in 42.2 per cent of cases. The disagreement was as high as 66.6 per cent with pathologists who rarely worked in the gynaecological field. This study casts serious doubt on the consistency of the histological diagnosis of hydatidiform mole made in any one laboratory and between different laboratories. It is suggested that in epidemiological studies the diagnosis should be made by a panel of pathologists using strict histological criteria and in an individual laboratory diagnosis should be made or confirmed by a pathologist experienced in gynaecological pathology.", "contents": "Discrepancies in the histological diagnosis of hydatidiform mole. Sections of tissue from 256 patients on which a histological diagnosis of hydatidiform mole had been made were reviewed by a visiting pathologist. There was agreement between the reporting pathologists and the visiting pathologist in only 55.1 per cent of cases, a less severe diagnosis was made by the visiting pathologist in 42.2 per cent of cases. The disagreement was as high as 66.6 per cent with pathologists who rarely worked in the gynaecological field. This study casts serious doubt on the consistency of the histological diagnosis of hydatidiform mole made in any one laboratory and between different laboratories. It is suggested that in epidemiological studies the diagnosis should be made by a panel of pathologists using strict histological criteria and in an individual laboratory diagnosis should be made or confirmed by a pathologist experienced in gynaecological pathology."}
{"id": "PMID:223627", "title": "Direct evidence for internalization of mitochondrial aspartate aminotransferase into mitoplasts.", "content": "Mitochondrial aspartate aminotransferase, an enzyme localized on the inner face of the inner mitochondrial membrane, is released into the intermembrane space upon addition of a \"movement effector\" (succinate, fumarate, pyruvate, or glutamate) [Waksman, A., & Rendon, A. (1974) Biochimie 56, 907-924]. After removal of the movement effector, 90% of the released enzyme rebound to mitoplasts. Lubrol fractionation showed that this bound activity was associated with the inner membrane. Internalization was demonstrated by using both enzymatic and molecular approaches. It was found that 70% of the reassociated enzyme became inaccessible from the outside of the mitoplast either to a nonpermeating substrate (NADH), to mild protease hydrolysis, or to recognition by a specific antibody. In contrast, in inside-out vesicles, the enzyme remained accessible to NADH, protease, and antibodies. Latency measurements performed at different temperatures on whole intact mitochondria confirmed the existence of reversible intermembrane movement of the enzyme in situ.", "contents": "Direct evidence for internalization of mitochondrial aspartate aminotransferase into mitoplasts. Mitochondrial aspartate aminotransferase, an enzyme localized on the inner face of the inner mitochondrial membrane, is released into the intermembrane space upon addition of a \"movement effector\" (succinate, fumarate, pyruvate, or glutamate) [Waksman, A., & Rendon, A. (1974) Biochimie 56, 907-924]. After removal of the movement effector, 90% of the released enzyme rebound to mitoplasts. Lubrol fractionation showed that this bound activity was associated with the inner membrane. Internalization was demonstrated by using both enzymatic and molecular approaches. It was found that 70% of the reassociated enzyme became inaccessible from the outside of the mitoplast either to a nonpermeating substrate (NADH), to mild protease hydrolysis, or to recognition by a specific antibody. In contrast, in inside-out vesicles, the enzyme remained accessible to NADH, protease, and antibodies. Latency measurements performed at different temperatures on whole intact mitochondria confirmed the existence of reversible intermembrane movement of the enzyme in situ."}
{"id": "PMID:223633", "title": "A rapid vectorial back reaction at the reaction centers of photosystem II in tris-washed chloroplasts induced by repetitive flash excitation.", "content": "In Tris-washed chloroplasts, completely lacking the oxygen-evolving capacity, absorption changes in the range of 420--560 nm induced by repetitive flash excitation have been measured in the presence and absence of electron donors. It was found: (1) At 520 nm flash-induced absorption changes are observed, which predominantly decay via a 100--200-mus exponential kinetics corresponding to that of the back reaction between the primary electron donor and acceptor of Photosystem II (Haveman, J. and Mathis, P. (1976) Biochim. Biophys. Acta 440, 346--355; Renger, G. and Wolff, Ch. (1976) Biochim. Biophys. Acta 423, 610--614). In the presence of hydroquinone/ascorbate as donor couple the amplitude is nearly doubled and the decay becomes significantly slowed down. (2) The difference spectrum of the absorption changes obtained in the presence of hydroquinone/ascorbate, which are sensitive to ionophores, is nearly identical with that of normal chloroplasts in the range of 460--560 nm (Emrich, H.M., Junge, W. and Witt, H.T. (1969) Z. Naturforsch. 24b, 114--1146). In the absence of hydroquinone/ascorbate the difference spectrum of the absorption changes, characterized by a 100--200-mus decay kinetics, differs in the range of 460--500 nm and by a hump in the range of 530--560 nm. The hump is shown to be attributable to the socalled C550 absorption change, which reflects the turnover of the primary acceptor of Photosystem II (van Gorkom, H.J.(1976) Thesis, Leiden), while the deviations in the range of 460--500 nm are understandable as to be due to the overlapping absorption changes of chlorphyll alpha II+. The problems arising with the latter explanation are discussed. (3) The electron transfer due to the rapid turnover at Photosystem II, which can be induced by flash groups with a short dark time between the flashes, is not able to energize the ATPase and to drive photophosphorylation. On the basis of the present results it is inferred, that in Tris-washed chloroplasts under repetitive flash excitation a rapid transmembrane vectorial electron shuttle takes place between the primary acceptor (X320) and donor (Chl alpha II) of Photosystem II, which is not able to energize the photophosphorylation. Furthermore, the data are shown to confirm the localization of X320 and Chl alpha II within the thylakoid membrane at the outer and inner side, respectively.", "contents": "A rapid vectorial back reaction at the reaction centers of photosystem II in tris-washed chloroplasts induced by repetitive flash excitation. In Tris-washed chloroplasts, completely lacking the oxygen-evolving capacity, absorption changes in the range of 420--560 nm induced by repetitive flash excitation have been measured in the presence and absence of electron donors. It was found: (1) At 520 nm flash-induced absorption changes are observed, which predominantly decay via a 100--200-mus exponential kinetics corresponding to that of the back reaction between the primary electron donor and acceptor of Photosystem II (Haveman, J. and Mathis, P. (1976) Biochim. Biophys. Acta 440, 346--355; Renger, G. and Wolff, Ch. (1976) Biochim. Biophys. Acta 423, 610--614). In the presence of hydroquinone/ascorbate as donor couple the amplitude is nearly doubled and the decay becomes significantly slowed down. (2) The difference spectrum of the absorption changes obtained in the presence of hydroquinone/ascorbate, which are sensitive to ionophores, is nearly identical with that of normal chloroplasts in the range of 460--560 nm (Emrich, H.M., Junge, W. and Witt, H.T. (1969) Z. Naturforsch. 24b, 114--1146). In the absence of hydroquinone/ascorbate the difference spectrum of the absorption changes, characterized by a 100--200-mus decay kinetics, differs in the range of 460--500 nm and by a hump in the range of 530--560 nm. The hump is shown to be attributable to the socalled C550 absorption change, which reflects the turnover of the primary acceptor of Photosystem II (van Gorkom, H.J.(1976) Thesis, Leiden), while the deviations in the range of 460--500 nm are understandable as to be due to the overlapping absorption changes of chlorphyll alpha II+. The problems arising with the latter explanation are discussed. (3) The electron transfer due to the rapid turnover at Photosystem II, which can be induced by flash groups with a short dark time between the flashes, is not able to energize the ATPase and to drive photophosphorylation. On the basis of the present results it is inferred, that in Tris-washed chloroplasts under repetitive flash excitation a rapid transmembrane vectorial electron shuttle takes place between the primary acceptor (X320) and donor (Chl alpha II) of Photosystem II, which is not able to energize the photophosphorylation. Furthermore, the data are shown to confirm the localization of X320 and Chl alpha II within the thylakoid membrane at the outer and inner side, respectively."}
{"id": "PMID:223634", "title": "Photoinduced charge separation in liposomes containing chlorophyll a. I. Photoreduction of copper(II) by potassium ascorbate through liposome bilayer containing purified chlorophyll a.", "content": "Photosensitivity of dispersion of phosphatidylcholine bilayer liposomes containing purified chlorophyll alpha was examined. The reduction of Cu(II) in the solution outside liposomes was observed upon illumination with visible light under anaerobic condition by means of ESR. The rate of photoreduction was significantly increased by a reductant, potassium ascorbate, localized in the solution of the opposite side of the membrane. The aciton spectrum of the reduction agreed with the absorption spectrum of chlorphyll a in the dispersion. The amount of bleach chlorophyll a was negligible compared with that of reduced (Cu(II). These facts lead to the conclusion that the potoinduced redox reactions at both the membrane-solution  interfaces are coupled with each other through the bilayer of each liposome. Kinetic analysis of the reactions based on a possible reaction scheme was carried out and some of the kinetic parameters were determined.", "contents": "Photoinduced charge separation in liposomes containing chlorophyll a. I. Photoreduction of copper(II) by potassium ascorbate through liposome bilayer containing purified chlorophyll a. Photosensitivity of dispersion of phosphatidylcholine bilayer liposomes containing purified chlorophyll alpha was examined. The reduction of Cu(II) in the solution outside liposomes was observed upon illumination with visible light under anaerobic condition by means of ESR. The rate of photoreduction was significantly increased by a reductant, potassium ascorbate, localized in the solution of the opposite side of the membrane. The aciton spectrum of the reduction agreed with the absorption spectrum of chlorphyll a in the dispersion. The amount of bleach chlorophyll a was negligible compared with that of reduced (Cu(II). These facts lead to the conclusion that the potoinduced redox reactions at both the membrane-solution  interfaces are coupled with each other through the bilayer of each liposome. Kinetic analysis of the reactions based on a possible reaction scheme was carried out and some of the kinetic parameters were determined."}
{"id": "PMID:223635", "title": "Ferrocyanide as electron donor to cytochrome aa3. Cytochrome c requirement for oxygen uptake.", "content": "1. In the absence of cytochrome c, ferrocyanide or ferrous sulphate reduces cytochrome c oxidase (EC 1.9.3.1), but no continuous oxygen uptake ensues, as it does with N,N,N',N'-tetramethyl-p-phenylenediamine or reduced phenazine methosulphate as reductants, unless a substoichiometric amount of cytochrome c or an excess of clupein is present. Cytochrome c cannot be replaced by porphyrin cytochrome c. 2. Cytochrome c, porphyrin cytochrome c and clupein all stimulate the reduction of cytochrome aa3 by ferrocyanide. 3. A model is proposed to explain these findings in which a high-affinity site for cytochrome c on the oxidase regulates the access of hydrophilic electron donors to a low-affinity site, and reduction via the high-affinity site is required for continuous oxygen uptake. 4. Furthermore, it is shown that upon reaction of oxidase with ferrocyanide, cyano-oxidase is formed.", "contents": "Ferrocyanide as electron donor to cytochrome aa3. Cytochrome c requirement for oxygen uptake. 1. In the absence of cytochrome c, ferrocyanide or ferrous sulphate reduces cytochrome c oxidase (EC 1.9.3.1), but no continuous oxygen uptake ensues, as it does with N,N,N',N'-tetramethyl-p-phenylenediamine or reduced phenazine methosulphate as reductants, unless a substoichiometric amount of cytochrome c or an excess of clupein is present. Cytochrome c cannot be replaced by porphyrin cytochrome c. 2. Cytochrome c, porphyrin cytochrome c and clupein all stimulate the reduction of cytochrome aa3 by ferrocyanide. 3. A model is proposed to explain these findings in which a high-affinity site for cytochrome c on the oxidase regulates the access of hydrophilic electron donors to a low-affinity site, and reduction via the high-affinity site is required for continuous oxygen uptake. 4. Furthermore, it is shown that upon reaction of oxidase with ferrocyanide, cyano-oxidase is formed."}
{"id": "PMID:223636", "title": "Regulation of cyclic photophosphorylation in Rhodospirillum rubrum by the redox state of nicotinamide-adenine dinucleotide.", "content": "We have investigated the effect of the redox state of added NAD on the rates of anaerobic cyclic photophosphorylation which are supported by membrane vesicles isolated from Rhodospirillum rubrum. As the redox potential of NAD was lowered, the activity decreased according to a typical potentiometric titration. The Nernst plot showed an apparent midpoint potential (E'o) of -350 mV and had a slope which corresponded to a two-electron transition. Besides, an almost identical potentiometric relationship was found to exist between the extent of light-elicited ATP formation in anaerobic suspensions of intact R. rubrum cells and the redox potential of intracellular NAD. These results suggest that physiological photophosphorylation in R. rubrum requires the oxidized form of a membrane-bound constituent (E'o = -350 mV) whose redox state is controlled by the redox state of cytoplasmic NAD.", "contents": "Regulation of cyclic photophosphorylation in Rhodospirillum rubrum by the redox state of nicotinamide-adenine dinucleotide. We have investigated the effect of the redox state of added NAD on the rates of anaerobic cyclic photophosphorylation which are supported by membrane vesicles isolated from Rhodospirillum rubrum. As the redox potential of NAD was lowered, the activity decreased according to a typical potentiometric titration. The Nernst plot showed an apparent midpoint potential (E'o) of -350 mV and had a slope which corresponded to a two-electron transition. Besides, an almost identical potentiometric relationship was found to exist between the extent of light-elicited ATP formation in anaerobic suspensions of intact R. rubrum cells and the redox potential of intracellular NAD. These results suggest that physiological photophosphorylation in R. rubrum requires the oxidized form of a membrane-bound constituent (E'o = -350 mV) whose redox state is controlled by the redox state of cytoplasmic NAD."}
{"id": "PMID:223637", "title": "The orientation of iron-sulfur clusters and a spin-coupled ubiquinone pair in the mitochondrial membrane.", "content": "Oriented multilayers made from beef heart and yeast mitochondria and submitochondrial particles were studied using electron paramagnetic resonance. EPR signals from membrane-bound iron-sulfur clusters and from a spin-coupled ubiquinone pair are highly orientation dependent, implying that these redox centers are fixed in the membrane at definite angles relative to the membrane plane. Typically the iron-iron axis (gz) of the binuclear iron-sulfur clusters is in the membrane plane. This finding is discussed in terms of the protein structure. The tetranuclear iron-sulfur clusters can have their gz axis either perpendicular or parallel to the membrane plane, but intermediate orientation was not observed.", "contents": "The orientation of iron-sulfur clusters and a spin-coupled ubiquinone pair in the mitochondrial membrane. Oriented multilayers made from beef heart and yeast mitochondria and submitochondrial particles were studied using electron paramagnetic resonance. EPR signals from membrane-bound iron-sulfur clusters and from a spin-coupled ubiquinone pair are highly orientation dependent, implying that these redox centers are fixed in the membrane at definite angles relative to the membrane plane. Typically the iron-iron axis (gz) of the binuclear iron-sulfur clusters is in the membrane plane. This finding is discussed in terms of the protein structure. The tetranuclear iron-sulfur clusters can have their gz axis either perpendicular or parallel to the membrane plane, but intermediate orientation was not observed."}
{"id": "PMID:223638", "title": "Electron-transfer processes in carboxy-cytochrome c oxidase after photodissociation of cytochrome a3 2+ . CO.", "content": "Under continuous illumination the CO binding curve of reduced carboxy-cytochrome c oxidase maintains the shape of the binding curve in the dark. The apparent dissociation constant calculated from the binding curves at various light intensities is a linear function of the light intensity. Marked differences are observed between the light-induced difference spectra of the fully reduced carboxy-cytochrome c oxidase and the mixed-valence carboxy-cytochrome c oxidase. These differences are enhanced in the presence of ferricyanide as an electron acceptor and are explained by partial oxidation of cytochrome a3 in the mixed-valence enzyme after photodissociation. Upon addition of CO to partially reduced formate cytochrome c oxidase (a2+a3 3+ . HCOOH) the cytochrome a3 2+. CO compound is formed completely with a concomitant oxidation of cytochrome a and the Cu associated with cytochrome a. During photodissociation of the CO compound the formate rebinds to cytochrome a3 and cytochrome a and its associated Cu are simultaneously reduced. These electron transfer processes are fully reversible since in the dark the a3 3+ . HCOOH compound is dissociated slowly with a concomitant formation of the a3 2+ . CO compound and oxidation of cytochrome a. When these experiments are carried out in the presence of cytochrome c, both cytochrome c and cytochrome a are reduced upon illumination of the mixed-valence carboxy-cytochrome c oxidase. In the dark both cytochrome c and cytochrome a are reoxidized when formate dissociates from cytochrome a3 and the a2+ 3 . CO compound is formed back. Thus, in this system we are able to reverse and to modulate the redox state of the different components of the final part of the respiratory chain by light.", "contents": "Electron-transfer processes in carboxy-cytochrome c oxidase after photodissociation of cytochrome a3 2+ . CO. Under continuous illumination the CO binding curve of reduced carboxy-cytochrome c oxidase maintains the shape of the binding curve in the dark. The apparent dissociation constant calculated from the binding curves at various light intensities is a linear function of the light intensity. Marked differences are observed between the light-induced difference spectra of the fully reduced carboxy-cytochrome c oxidase and the mixed-valence carboxy-cytochrome c oxidase. These differences are enhanced in the presence of ferricyanide as an electron acceptor and are explained by partial oxidation of cytochrome a3 in the mixed-valence enzyme after photodissociation. Upon addition of CO to partially reduced formate cytochrome c oxidase (a2+a3 3+ . HCOOH) the cytochrome a3 2+. CO compound is formed completely with a concomitant oxidation of cytochrome a and the Cu associated with cytochrome a. During photodissociation of the CO compound the formate rebinds to cytochrome a3 and cytochrome a and its associated Cu are simultaneously reduced. These electron transfer processes are fully reversible since in the dark the a3 3+ . HCOOH compound is dissociated slowly with a concomitant formation of the a3 2+ . CO compound and oxidation of cytochrome a. When these experiments are carried out in the presence of cytochrome c, both cytochrome c and cytochrome a are reduced upon illumination of the mixed-valence carboxy-cytochrome c oxidase. In the dark both cytochrome c and cytochrome a are reoxidized when formate dissociates from cytochrome a3 and the a2+ 3 . CO compound is formed back. Thus, in this system we are able to reverse and to modulate the redox state of the different components of the final part of the respiratory chain by light."}
{"id": "PMID:223640", "title": "Purine metabolism in microplasmodia of Physarum polycephalum.", "content": "The uptake and utilization of purine nucleosides and purines in microplasmodia of Physarum polycephalum were investigated. The results revealed a unique pattern, namely that exogenous purine nucleosides are readily taken up and metabolised, while free purine bases are hardly taken up. The pathways of incorporation have been elucidated in studies with whole cells and with cell-free extracts. The ribonucleosides (adenosine, inosine and guanosine) can be converted into ribonucleotides in two ways; either directly catalysed by a kinase or by a phosphorolytic cleavage to the free base (adenine, hypoxanthine and guanine respectively) which can then be activated by a purine phosphoribosyltransferase. Apparently the purine phosphoribosyltransferases do not react with exogenous purine bases. The deoxyribonucleosides (deoxyadenosine, deoxyinosine and deoxyguanosine) are also phosphorolysed by purine nucleoside phosphorylase to adenine, hypoxanthine and guanine respectively. A portion of deoxyadenosine is directly phosphorylated to dAMP. It appears that only a minor part of the soluble nucleotide pool can be synthesised from exogenous supplied nucleosides and that none of the deoxyribonucleosides specifically label DNA. There is no catabolism of the purine moiety. In agreement with the above findings, we have found that analoguees of purine nucleosides are more toxic than their corresponding purine base analogues.", "contents": "Purine metabolism in microplasmodia of Physarum polycephalum. The uptake and utilization of purine nucleosides and purines in microplasmodia of Physarum polycephalum were investigated. The results revealed a unique pattern, namely that exogenous purine nucleosides are readily taken up and metabolised, while free purine bases are hardly taken up. The pathways of incorporation have been elucidated in studies with whole cells and with cell-free extracts. The ribonucleosides (adenosine, inosine and guanosine) can be converted into ribonucleotides in two ways; either directly catalysed by a kinase or by a phosphorolytic cleavage to the free base (adenine, hypoxanthine and guanine respectively) which can then be activated by a purine phosphoribosyltransferase. Apparently the purine phosphoribosyltransferases do not react with exogenous purine bases. The deoxyribonucleosides (deoxyadenosine, deoxyinosine and deoxyguanosine) are also phosphorolysed by purine nucleoside phosphorylase to adenine, hypoxanthine and guanine respectively. A portion of deoxyadenosine is directly phosphorylated to dAMP. It appears that only a minor part of the soluble nucleotide pool can be synthesised from exogenous supplied nucleosides and that none of the deoxyribonucleosides specifically label DNA. There is no catabolism of the purine moiety. In agreement with the above findings, we have found that analoguees of purine nucleosides are more toxic than their corresponding purine base analogues."}
{"id": "PMID:223641", "title": "Early changes in the synthesis of proteins with affinity for single-stranded DNA during the onset of transformation in NRK cells.", "content": "Early alterations in the synthesis of proteins which bind to single-stranded DNA have been examined following the onset of transformation in NRK cells transformed by a heat-sensitive mutant (ts339) of Rous sarcoma virus. Transformation was initiated by shifting quiescent cultures from nonpermissive to permissive temperatures. Cultures were prelabelled with [3H]leucine for several generations at the non-permissive temperature, and with [35S]methionine at times after shift to the permissive temperature. Cytosol extracts were passed through sequential columns of double-stranded and single-stranded DNA bound to cellulose. Within the first hour of transformation there was an increase in the synthetic rate of proteins binding tightly to single-stranded DNA, but not to double-stranded DNA. More loosely bound protein fractions showed no such early synthetic increase. Electrophoresis of the fraction eluted from single stranded DNA-cellulose with 2 M NaCl demonstrated the presence of a major protein of 93 000 daltons, which comprised more than 0.1% of the cytosol protein. The synthesis of the 93 000 dalton protein increased continuously over the first 4 h interval after the onset of transformation. The synthetic rate of a 35 000 dalton protein, a major DNA-binding polypeptide found in mammalian cells, began to increase after a 1-h lag, following the onset of transformation. The protein fraction containing the 93 000 dalton protein had considerable unwinding activity, depressing the melting temperature of poly(dA-dT) by 39 degrees C. The protein fraction containing the bulk of the 35 000 dalton protein did not have unwinding activity. Transformation-induced DNA synthesis was measured in cells made permeable to deoxyribonucleoside triphosphates at times after shift to the permissive temperature. It was determined that synthesis of DNA began within the first 1--2 h after the onset of transformation. We conclude that the early transformation-associated synthesis of SS93 and perhaps other proteins binding to single-stranded DNA may be related to early transformation-associated changes preparatory to DNA replication and subsequent growth.", "contents": "Early changes in the synthesis of proteins with affinity for single-stranded DNA during the onset of transformation in NRK cells. Early alterations in the synthesis of proteins which bind to single-stranded DNA have been examined following the onset of transformation in NRK cells transformed by a heat-sensitive mutant (ts339) of Rous sarcoma virus. Transformation was initiated by shifting quiescent cultures from nonpermissive to permissive temperatures. Cultures were prelabelled with [3H]leucine for several generations at the non-permissive temperature, and with [35S]methionine at times after shift to the permissive temperature. Cytosol extracts were passed through sequential columns of double-stranded and single-stranded DNA bound to cellulose. Within the first hour of transformation there was an increase in the synthetic rate of proteins binding tightly to single-stranded DNA, but not to double-stranded DNA. More loosely bound protein fractions showed no such early synthetic increase. Electrophoresis of the fraction eluted from single stranded DNA-cellulose with 2 M NaCl demonstrated the presence of a major protein of 93 000 daltons, which comprised more than 0.1% of the cytosol protein. The synthesis of the 93 000 dalton protein increased continuously over the first 4 h interval after the onset of transformation. The synthetic rate of a 35 000 dalton protein, a major DNA-binding polypeptide found in mammalian cells, began to increase after a 1-h lag, following the onset of transformation. The protein fraction containing the 93 000 dalton protein had considerable unwinding activity, depressing the melting temperature of poly(dA-dT) by 39 degrees C. The protein fraction containing the bulk of the 35 000 dalton protein did not have unwinding activity. Transformation-induced DNA synthesis was measured in cells made permeable to deoxyribonucleoside triphosphates at times after shift to the permissive temperature. It was determined that synthesis of DNA began within the first 1--2 h after the onset of transformation. We conclude that the early transformation-associated synthesis of SS93 and perhaps other proteins binding to single-stranded DNA may be related to early transformation-associated changes preparatory to DNA replication and subsequent growth."}
{"id": "PMID:223642", "title": "'Cap' structures in maize poly(A)-containing RNA.", "content": "Poly(A)-containing RNA was isolated from maize embryos by chromatography on columns of oligo(dT)-cellulose and exhaustively digested with ribonucleases T2, T1, and A. Fractionation of the digests by two-dimensional electrophoresis revealed the presence of three 7-methylguanosine-terminated 'cap structures' of the type m7GpppNp.", "contents": "'Cap' structures in maize poly(A)-containing RNA. Poly(A)-containing RNA was isolated from maize embryos by chromatography on columns of oligo(dT)-cellulose and exhaustively digested with ribonucleases T2, T1, and A. Fractionation of the digests by two-dimensional electrophoresis revealed the presence of three 7-methylguanosine-terminated 'cap structures' of the type m7GpppNp."}
{"id": "PMID:223643", "title": "Immunofluorescence localization of plasma protein synthesis in cultured chick hepatocytes.", "content": "Fibrinogen, albumin and the major apoprotein of high density lipoprotein (apoprotein A) were localized in a primary embryonic chick liver cell culture by indirect immunofluorescence staining. Changes in the pattern of plasma protein synthesis under a variety of conditions, as measured by the accumulation of secreted plasma proteins in the culture medium, could be studied at the cellular level because relative fluorescence intensities were shown to reflect synthetic rates. In all cases studied, the immunofluorescence of the hepatic parenchymal cells was of a similar intensity throughout the monolayers, indicating that the cells in culture constitute a homogeneous population with respect to the synthesis of these plasma proteins.", "contents": "Immunofluorescence localization of plasma protein synthesis in cultured chick hepatocytes. Fibrinogen, albumin and the major apoprotein of high density lipoprotein (apoprotein A) were localized in a primary embryonic chick liver cell culture by indirect immunofluorescence staining. Changes in the pattern of plasma protein synthesis under a variety of conditions, as measured by the accumulation of secreted plasma proteins in the culture medium, could be studied at the cellular level because relative fluorescence intensities were shown to reflect synthetic rates. In all cases studied, the immunofluorescence of the hepatic parenchymal cells was of a similar intensity throughout the monolayers, indicating that the cells in culture constitute a homogeneous population with respect to the synthesis of these plasma proteins."}
{"id": "PMID:223644", "title": "Dissociation of apolipoprotein A-I from porcine and bovine high density lipoproteins by guanidine hydrochloride.", "content": "Dissociation of apolipoprotein A-I from pig and steer high density lipoproteins (HDL) deficient in apoA-II was determined by exposing native HDL fractions to 6 M guanidine hydrochloride (Gdn-HCl) at 37 degrees C for periods from 5 min to 18 h. Bovine high density lipoprotein (HDL-B) was isolated at d 1.063--1.100 g/ml while porcine high density lipoprotein (HDL-P) was isolated at d 1.125--1.21 g/ml. Incubation for 5 min with Gdn-HCl resulted in a 45 and 3% loss of apo-A-I from HDL-P and HDL-B, respectively. Exposure to the denaturant for 3 h resulted in a 75% loss of apoA-I from HDL-P and a 30% loss from HDL-B. Analytic ultracentrifugation, patterns paralleled the degree of apoA-I dissociation from each HDL species. The initial flotation peak for HDL-P shifted from F degrees 1.20 2.68 to F degrees 1.20 10.75 after 3 h exposure while HDL-B showed only a small shift from F degrees 1.20 8.30 to F degrees 1.20 8.96 after 3 h exposure. HDL-P particle diameter increased 25% after 5 min of Gdn-HCl treatment and large, flattened structures predominated after 3 h. There was no changes in the size of HDL-B after 5 min exposure and only 16% increase in particle diameter after 3 h. The difference in behavior of HDL-B and HDL-P to Gdn-HCl exposure is discussed in terms of differences in apolipoprotein A-I amino acid composition, interaction of apolipoprotein A-I with phospholipids and the possible involvement of the cholesteryl ester core.", "contents": "Dissociation of apolipoprotein A-I from porcine and bovine high density lipoproteins by guanidine hydrochloride. Dissociation of apolipoprotein A-I from pig and steer high density lipoproteins (HDL) deficient in apoA-II was determined by exposing native HDL fractions to 6 M guanidine hydrochloride (Gdn-HCl) at 37 degrees C for periods from 5 min to 18 h. Bovine high density lipoprotein (HDL-B) was isolated at d 1.063--1.100 g/ml while porcine high density lipoprotein (HDL-P) was isolated at d 1.125--1.21 g/ml. Incubation for 5 min with Gdn-HCl resulted in a 45 and 3% loss of apo-A-I from HDL-P and HDL-B, respectively. Exposure to the denaturant for 3 h resulted in a 75% loss of apoA-I from HDL-P and a 30% loss from HDL-B. Analytic ultracentrifugation, patterns paralleled the degree of apoA-I dissociation from each HDL species. The initial flotation peak for HDL-P shifted from F degrees 1.20 2.68 to F degrees 1.20 10.75 after 3 h exposure while HDL-B showed only a small shift from F degrees 1.20 8.30 to F degrees 1.20 8.96 after 3 h exposure. HDL-P particle diameter increased 25% after 5 min of Gdn-HCl treatment and large, flattened structures predominated after 3 h. There was no changes in the size of HDL-B after 5 min exposure and only 16% increase in particle diameter after 3 h. The difference in behavior of HDL-B and HDL-P to Gdn-HCl exposure is discussed in terms of differences in apolipoprotein A-I amino acid composition, interaction of apolipoprotein A-I with phospholipids and the possible involvement of the cholesteryl ester core."}
{"id": "PMID:223645", "title": "Effect of lipolytic agents on adenosine and AMP formation by fat cells.", "content": "The release and metabolism of adenosine was examined using rat fat cells in which the nucleotide pool has been labeled by incubation with radioactive adenine. The accumulation of adenosine in the medium was near maximal at the start of the incubation and increased only slightly thereafter. Adenosine was rapidly deaminated to inosine and subsequently oxidized to uric acid. In the presence of allopurinol, and inhibitor of xanthine dehydrogenase, hypoxanthine accumulated in the medium as the end-product of adenosine catabolism. Adenosine accumulated in the medium only if fat cells were incubated in the presence of erythro-9-(2-hydroxy-3-nonyl)adenine, an inhibitor of adenosine deaminase. Even in the presence of this inhibitor there was no acceleration of adenosine release by norepinephrine in the presence of theophylline. However, there was an increase in labeled intracellular AMP accumulation by norepinephrine plus theophylline. The increase in labeled AMP correlated with the final free fatty acid to albumin ratio suggesting that the rise in AMP was related to an accumulation of intracellular free fatty acids. The addition of sodium oleate to the medium mimicked the effect of norepinephrine plus theophylline on the accumulation of labeled AMP. These results indicate that AMP rather than adenosine accumulates in isolated fat cells during incubation with lipolytic agents.", "contents": "Effect of lipolytic agents on adenosine and AMP formation by fat cells. The release and metabolism of adenosine was examined using rat fat cells in which the nucleotide pool has been labeled by incubation with radioactive adenine. The accumulation of adenosine in the medium was near maximal at the start of the incubation and increased only slightly thereafter. Adenosine was rapidly deaminated to inosine and subsequently oxidized to uric acid. In the presence of allopurinol, and inhibitor of xanthine dehydrogenase, hypoxanthine accumulated in the medium as the end-product of adenosine catabolism. Adenosine accumulated in the medium only if fat cells were incubated in the presence of erythro-9-(2-hydroxy-3-nonyl)adenine, an inhibitor of adenosine deaminase. Even in the presence of this inhibitor there was no acceleration of adenosine release by norepinephrine in the presence of theophylline. However, there was an increase in labeled intracellular AMP accumulation by norepinephrine plus theophylline. The increase in labeled AMP correlated with the final free fatty acid to albumin ratio suggesting that the rise in AMP was related to an accumulation of intracellular free fatty acids. The addition of sodium oleate to the medium mimicked the effect of norepinephrine plus theophylline on the accumulation of labeled AMP. These results indicate that AMP rather than adenosine accumulates in isolated fat cells during incubation with lipolytic agents."}
{"id": "PMID:223646", "title": "Lipoprotein lipase of cultured mesenchymal rat heart cells. IV. Modulation of enzyme activity by VLDL added to the culture medium.", "content": "Lipoprotein lipase activity was studied in rat heart cell cultures grown in the presence of 20% fetal calf and horse serum and a medium concentration of triacylglycerol of 0.03 mg/ml. After 6--8 days, when the enzyme activity had reached high levels, the cells were incubated for 24 h in a medium containing 20% serum derived from fasted or fed rats. No change in enzyme activity occurred in the presence of fasted rat serum, but a 50% fall was observed with fed rat serium. When the complete culture medium was supplemented with rat plasma VLDL (0.075--0.75 mg triacylglycerol) a pronounced decrease in lipoprotein lipase activity occurred after 3--5 h of incubation. Similar extent of enzyme fall was observed also in the presence of triacylglycerol-rich lipoproteins isolated from rat plasma after feeding of safflower oil or lard, even though the fatty acid composition of the triacylgylcerol varied markedly. As the addition of VLDL to the culture medium resulted in a lesser fall of heparin releasable than residual activity it seems that there was no direct inhibition of surface bound enzyme activity and that the transport of the enzyme to the cell surface was not affected. These data indicate that addition of VLDL to the culture medium resulted in a fall in enzyme synthesis, while total protein synthesis as determined by incorporation of [3H]leucine, remained unchanged. This inhibition could be reproduced by increasing free fatty acid concentration of the medium, however addition of excess albumin to VLDL-containing medium did not prevent the fall in enzyme activity. The present results obtained with cultured rat hearts cells suggest that in vivo plasma levels of triacylglycerol-rich lipoproteins could modulate the lipoproteins could modulate the lipoprotein lipase activity of the heart.", "contents": "Lipoprotein lipase of cultured mesenchymal rat heart cells. IV. Modulation of enzyme activity by VLDL added to the culture medium. Lipoprotein lipase activity was studied in rat heart cell cultures grown in the presence of 20% fetal calf and horse serum and a medium concentration of triacylglycerol of 0.03 mg/ml. After 6--8 days, when the enzyme activity had reached high levels, the cells were incubated for 24 h in a medium containing 20% serum derived from fasted or fed rats. No change in enzyme activity occurred in the presence of fasted rat serum, but a 50% fall was observed with fed rat serium. When the complete culture medium was supplemented with rat plasma VLDL (0.075--0.75 mg triacylglycerol) a pronounced decrease in lipoprotein lipase activity occurred after 3--5 h of incubation. Similar extent of enzyme fall was observed also in the presence of triacylglycerol-rich lipoproteins isolated from rat plasma after feeding of safflower oil or lard, even though the fatty acid composition of the triacylgylcerol varied markedly. As the addition of VLDL to the culture medium resulted in a lesser fall of heparin releasable than residual activity it seems that there was no direct inhibition of surface bound enzyme activity and that the transport of the enzyme to the cell surface was not affected. These data indicate that addition of VLDL to the culture medium resulted in a fall in enzyme synthesis, while total protein synthesis as determined by incorporation of [3H]leucine, remained unchanged. This inhibition could be reproduced by increasing free fatty acid concentration of the medium, however addition of excess albumin to VLDL-containing medium did not prevent the fall in enzyme activity. The present results obtained with cultured rat hearts cells suggest that in vivo plasma levels of triacylglycerol-rich lipoproteins could modulate the lipoproteins could modulate the lipoprotein lipase activity of the heart."}
{"id": "PMID:223647", "title": "The nature of the nitric oxide complexes of lipoxygenase.", "content": "The NO complex of lipoxygenase with EPR signals near g = 4.0 is an S = 3/2 system with D approximately 15 cm-1 similar to Fe2+-EDTA-NO. This may result from antiferromagnetic coupling of axial (D greater than E) high spin ferrous iron to NO. The other NO complex of lipoxygenase, with EPR signals below ge, may result from rhombic high spin ferrous iron coupled to NO with D greater than J. The quenching of both signals by a hydroperoxy derivative of linoleic acid probably represents replacement of NO by an oxygen ligand.", "contents": "The nature of the nitric oxide complexes of lipoxygenase. The NO complex of lipoxygenase with EPR signals near g = 4.0 is an S = 3/2 system with D approximately 15 cm-1 similar to Fe2+-EDTA-NO. This may result from antiferromagnetic coupling of axial (D greater than E) high spin ferrous iron to NO. The other NO complex of lipoxygenase, with EPR signals below ge, may result from rhombic high spin ferrous iron coupled to NO with D greater than J. The quenching of both signals by a hydroperoxy derivative of linoleic acid probably represents replacement of NO by an oxygen ligand."}
{"id": "PMID:223649", "title": "Cyclic AMP-adenosine binding protein/S-adenosylhomocysteinase from mouse liver. A fraction of adenosine bound is converted to adenine.", "content": "1. Adenosine bound to the cyclic AMP-adenosine binding protein/S-adenosylhomocysteinase from mouse liver was partly converted to a product which was identified as adenine in four chromatographic systems. Ribose was formed in equivalent amounts. 2. The time course of the reaction was characterized by an initial burst phase lasting for less than one second followed by a slow progressive phase. The reaction was partly reversed by prolonged incubation, slow denaturation of the protein, dilution of the incubation mixture and removal of adenosine by converting it to inosine by the enzyme adenosine deaminase. 3. Both the ATP-treated (Ueland, P.M. and D\u00f8skeland, S.O. (1978) Arch. Biochem. Biophys. 185, 195--203) and the non-treated protein were subjected to polyacrylamide gel electrophoresis at pH 8.8. The adenosine-adenine, the cyclic AMP binding activities and the conversion activity comigrated with the main protein band, indicating that these properties reside on the same protein molecule. 4. Adenine generated by hydrolysis of adenosine was mainly bound to the protein as judged by nearly complete reversion of the conversion upon dilution in the presence of excess unlabelled adenine and by Sephadex G-25 chromatography. 5. The conversion of adenosine to inosine by the enzyme adenosine deaminase was decreased in the presence of the binding protein. 6. Adenine formation could also be demonstrated under condition of enzymic formation of S-adenosylhomocysteine, i.e. in the presence of hymocysteine.", "contents": "Cyclic AMP-adenosine binding protein/S-adenosylhomocysteinase from mouse liver. A fraction of adenosine bound is converted to adenine. 1. Adenosine bound to the cyclic AMP-adenosine binding protein/S-adenosylhomocysteinase from mouse liver was partly converted to a product which was identified as adenine in four chromatographic systems. Ribose was formed in equivalent amounts. 2. The time course of the reaction was characterized by an initial burst phase lasting for less than one second followed by a slow progressive phase. The reaction was partly reversed by prolonged incubation, slow denaturation of the protein, dilution of the incubation mixture and removal of adenosine by converting it to inosine by the enzyme adenosine deaminase. 3. Both the ATP-treated (Ueland, P.M. and D\u00f8skeland, S.O. (1978) Arch. Biochem. Biophys. 185, 195--203) and the non-treated protein were subjected to polyacrylamide gel electrophoresis at pH 8.8. The adenosine-adenine, the cyclic AMP binding activities and the conversion activity comigrated with the main protein band, indicating that these properties reside on the same protein molecule. 4. Adenine generated by hydrolysis of adenosine was mainly bound to the protein as judged by nearly complete reversion of the conversion upon dilution in the presence of excess unlabelled adenine and by Sephadex G-25 chromatography. 5. The conversion of adenosine to inosine by the enzyme adenosine deaminase was decreased in the presence of the binding protein. 6. Adenine formation could also be demonstrated under condition of enzymic formation of S-adenosylhomocysteine, i.e. in the presence of hymocysteine."}
{"id": "PMID:223650", "title": "Independent expression of cardiac type I and II cyclic AMP-dependent protein kinase during murine embryogenesis and postnatal development.", "content": "The amount of total cyclic AMP-dependent protein kinase and of the protein kinase isozymes present in mouse heart changes during development. During embryogenesis, the total cardiac protein kinase activity increases most markedly during the 6 days prior to birth. A maximum kinase level is achieved in the 7 day-old neonate, and then activity progressively declines to an adult level approximating that of the mid-embryo. The type II kinase exhibits a moderate increase during late embryogenesis which declines by the time of birth. The type I isozyme increases throughout embryogenesis and the first neonatal week to a maximum specific activity five-fold higher than the mid-embryogenesis level. The isozyme level then falls to an adult activity similar to the mid-embryonic. These changes in isozyme profile are reflected in a changing type I to type II kinase ratio of 1.1 at 13--14 days embryogenesis, 2.4 at birth, 3.0 in the 7 day-old neonates, and 1 in the adult heart. Thus, the two protein kinase isozymes change in association with the developmental process in an independent fashion.", "contents": "Independent expression of cardiac type I and II cyclic AMP-dependent protein kinase during murine embryogenesis and postnatal development. The amount of total cyclic AMP-dependent protein kinase and of the protein kinase isozymes present in mouse heart changes during development. During embryogenesis, the total cardiac protein kinase activity increases most markedly during the 6 days prior to birth. A maximum kinase level is achieved in the 7 day-old neonate, and then activity progressively declines to an adult level approximating that of the mid-embryo. The type II kinase exhibits a moderate increase during late embryogenesis which declines by the time of birth. The type I isozyme increases throughout embryogenesis and the first neonatal week to a maximum specific activity five-fold higher than the mid-embryogenesis level. The isozyme level then falls to an adult activity similar to the mid-embryonic. These changes in isozyme profile are reflected in a changing type I to type II kinase ratio of 1.1 at 13--14 days embryogenesis, 2.4 at birth, 3.0 in the 7 day-old neonates, and 1 in the adult heart. Thus, the two protein kinase isozymes change in association with the developmental process in an independent fashion."}
{"id": "PMID:223651", "title": "Induction of N-acetylmannosamine catabolic pathway in yeast.", "content": "N-Acetylmannosamine kinase activity is absent from yeast cells grown on N-acetylmannosamine. However, other enzymes of the catabolic pathway, namely, N-acetylmannosamine-2-epimerase, N-acetylglucosamine kinase and glucosamine-6-phosphate deaminase are induced. In addition, a high affinity uptake system (permease) for the uptake of N-acetylglucosamine is synthesized under these conditions. The presence of either N-acetylmannosamine or N-acetylglucosamine as inducer is essential for the induced synthesis of these enzymes. The enzyme synthesis stops and their concentration in the cells declines rapidly as soon as inducer is removed from the medium. N-Acetyl-D-galactosamine can also induce all these enzymes except for N-acetylmannosamine-2-epimerase, suggesting the convergence of catabolic pathways for both the aminosugars at N-acetyl-D-glycosamine. Experiments with inhibitors of macromolecule synthesis suggest that the snythesis of RNA and protein is necessary for the induction of these cyzymes whereas the synthesis of DNA is not.", "contents": "Induction of N-acetylmannosamine catabolic pathway in yeast. N-Acetylmannosamine kinase activity is absent from yeast cells grown on N-acetylmannosamine. However, other enzymes of the catabolic pathway, namely, N-acetylmannosamine-2-epimerase, N-acetylglucosamine kinase and glucosamine-6-phosphate deaminase are induced. In addition, a high affinity uptake system (permease) for the uptake of N-acetylglucosamine is synthesized under these conditions. The presence of either N-acetylmannosamine or N-acetylglucosamine as inducer is essential for the induced synthesis of these enzymes. The enzyme synthesis stops and their concentration in the cells declines rapidly as soon as inducer is removed from the medium. N-Acetyl-D-galactosamine can also induce all these enzymes except for N-acetylmannosamine-2-epimerase, suggesting the convergence of catabolic pathways for both the aminosugars at N-acetyl-D-glycosamine. Experiments with inhibitors of macromolecule synthesis suggest that the snythesis of RNA and protein is necessary for the induction of these cyzymes whereas the synthesis of DNA is not."}
{"id": "PMID:223652", "title": "The dark respiration of Anacystis nidulans. Production of HCN from histidine and oxidation of basic amino acids.", "content": "The basic amino acids, L-arginine, L-lysine, LO-irnithine, and to a lesser extent L-histidine, strongly stimulate the O2 uptake of cell suspensions of the blue-green alga or cyanobacterium anacystis nidulans. In the case of L-histidine, the extra O2 consumption is associated with the formation in vivo of small amounts of HCN, particularly in an atmosphere of O2. The enzyme responsible for both the stimulated O2 uptake with the basic amino acids and the formation of HCN from histidine has been isolated and identified as an L-amino acid oxidase specific for the basic amino acids. The purification (15 000-fold) of this enzyme is described. The isolated enzyme is inhibited by o-phenanthroline, which has a similar inhibitory effect on the O2 uptake of cell suspensions with (and without) added amino acids. The basic amino acid oxidase, which is not inhibited by HCN, can be regarded as an 'alternate' oxidase in A. nidulans. An oxidase sensitive to HCN is apparently also operative. At high concentrations of lysine or arginine added HCN can almost double the initial rate of O2 consumption of cell suspensions. This can be attributed to the inhibition of catalase by HCN. At low concentrations of the amino acids, and with more prolonged incubation time, HCN becomes inhibitory. One interpretation could be that the HCN-sensitive terminal oxidase is also involved in the extra O2 uptake elicited by the basic amino acids, but other interpretations are possible. The extra O2 uptake elicited by histidine is almost completely inhibited by HCN, which is consistent with the finding that histidine is a relatively poor substrate for the basic amino acid oxidase.", "contents": "The dark respiration of Anacystis nidulans. Production of HCN from histidine and oxidation of basic amino acids. The basic amino acids, L-arginine, L-lysine, LO-irnithine, and to a lesser extent L-histidine, strongly stimulate the O2 uptake of cell suspensions of the blue-green alga or cyanobacterium anacystis nidulans. In the case of L-histidine, the extra O2 consumption is associated with the formation in vivo of small amounts of HCN, particularly in an atmosphere of O2. The enzyme responsible for both the stimulated O2 uptake with the basic amino acids and the formation of HCN from histidine has been isolated and identified as an L-amino acid oxidase specific for the basic amino acids. The purification (15 000-fold) of this enzyme is described. The isolated enzyme is inhibited by o-phenanthroline, which has a similar inhibitory effect on the O2 uptake of cell suspensions with (and without) added amino acids. The basic amino acid oxidase, which is not inhibited by HCN, can be regarded as an 'alternate' oxidase in A. nidulans. An oxidase sensitive to HCN is apparently also operative. At high concentrations of lysine or arginine added HCN can almost double the initial rate of O2 consumption of cell suspensions. This can be attributed to the inhibition of catalase by HCN. At low concentrations of the amino acids, and with more prolonged incubation time, HCN becomes inhibitory. One interpretation could be that the HCN-sensitive terminal oxidase is also involved in the extra O2 uptake elicited by the basic amino acids, but other interpretations are possible. The extra O2 uptake elicited by histidine is almost completely inhibited by HCN, which is consistent with the finding that histidine is a relatively poor substrate for the basic amino acid oxidase."}
{"id": "PMID:223654", "title": "[Free radicals formed during UV-irradiation of biological membrane lipids].", "content": "Formation of free radicals under UV-irradiation of egg phosphatidyl choline, and synthetic phosphatidyl cholines and their analogs, as well as of their model compounds was studied. When saturated fat lipids are UV-irradiated radicals--CH2CH2 are accumulated at the expense of the breakage of--CH2CH2--COOH-bond. Radicals CH3--OCH2, HCO are formed in aminoalcohols due to the breakage of --OCH2--CH2N+(CH3)3- and--CH2--N+(CH3)3-bonds. It has been found that in natural and synthetic phospholipids radicals are formed in the course of photochemical reactions in complex ether and amine groups. The mechanism of radical formation is discussed.", "contents": "[Free radicals formed during UV-irradiation of biological membrane lipids]. Formation of free radicals under UV-irradiation of egg phosphatidyl choline, and synthetic phosphatidyl cholines and their analogs, as well as of their model compounds was studied. When saturated fat lipids are UV-irradiated radicals--CH2CH2 are accumulated at the expense of the breakage of--CH2CH2--COOH-bond. Radicals CH3--OCH2, HCO are formed in aminoalcohols due to the breakage of --OCH2--CH2N+(CH3)3- and--CH2--N+(CH3)3-bonds. It has been found that in natural and synthetic phospholipids radicals are formed in the course of photochemical reactions in complex ether and amine groups. The mechanism of radical formation is discussed."}
{"id": "PMID:223656", "title": "[Qualitative study of a mathematical model of the open futile cycle fructose-6-P--fructose-1,6-P2].", "content": "A simple mathematical model of the open futile cycle fructose-6-P in equilibrium fructose-1,6-P2 in which the fructose bisphosphatase reaction is inhibited by excess of its substrate has been analysed. A detailed qualitative investigation of the model shows that it possesses all properties characteristic of any other dynamical system of the second order which has a hysteretic major null-cline, 1 to 3 steady states and is capable of generating self-oscillations.", "contents": "[Qualitative study of a mathematical model of the open futile cycle fructose-6-P--fructose-1,6-P2]. A simple mathematical model of the open futile cycle fructose-6-P in equilibrium fructose-1,6-P2 in which the fructose bisphosphatase reaction is inhibited by excess of its substrate has been analysed. A detailed qualitative investigation of the model shows that it possesses all properties characteristic of any other dynamical system of the second order which has a hysteretic major null-cline, 1 to 3 steady states and is capable of generating self-oscillations."}
{"id": "PMID:223657", "title": "[Quantitative model of human erythrocyte glycolysis. Relationship between erythrocyte energy metabolism and Na+, K+-ATPase activity].", "content": "The influence of the changes of the transport Na+, K+-ATPase activity on the human red blood cell (RBC) glycolysis was studied. Two different types of energetic regulation were found out under the strophanthin inhibition. A decrease of ATP comsumption results in a drop of glucose consumption and lactate production in the first type regulation of RBC. In the second type regulation of RBC the glucose consumption does not change after ATPase inhibition and the excess metabolic flux is directed through the hexosemonophosphate shunt. In both cases the resulting decrease of ATP production leads to the ATP level stabilization. An increase of potassium ions concentration in the external medium does not influence the RBC glycolysis. The valinomycin added increases the glucose consumption and the lactate production. The cell volume decreases under the effect of valinomycin.", "contents": "[Quantitative model of human erythrocyte glycolysis. Relationship between erythrocyte energy metabolism and Na+, K+-ATPase activity]. The influence of the changes of the transport Na+, K+-ATPase activity on the human red blood cell (RBC) glycolysis was studied. Two different types of energetic regulation were found out under the strophanthin inhibition. A decrease of ATP comsumption results in a drop of glucose consumption and lactate production in the first type regulation of RBC. In the second type regulation of RBC the glucose consumption does not change after ATPase inhibition and the excess metabolic flux is directed through the hexosemonophosphate shunt. In both cases the resulting decrease of ATP production leads to the ATP level stabilization. An increase of potassium ions concentration in the external medium does not influence the RBC glycolysis. The valinomycin added increases the glucose consumption and the lactate production. The cell volume decreases under the effect of valinomycin."}
{"id": "PMID:223658", "title": "[Spin label study of the temperature stability of plant fibers].", "content": "Temperature relationship of rotation diffusion parameters of radical connected to different varieties of cotton filament, isolated from normal and with affected cotton was studied. It has been found that structural transitions accompanied with a markable increase of radical rotation diffusion in all the samples studied, proceed at definite temperatures. For filament samples from wilt-affected plants temperatures at which structural transitions proceed are higher as compared to the filaments taken from normal plants. This phenomenon point to higher micro rigidity of wilt-affected plants.", "contents": "[Spin label study of the temperature stability of plant fibers]. Temperature relationship of rotation diffusion parameters of radical connected to different varieties of cotton filament, isolated from normal and with affected cotton was studied. It has been found that structural transitions accompanied with a markable increase of radical rotation diffusion in all the samples studied, proceed at definite temperatures. For filament samples from wilt-affected plants temperatures at which structural transitions proceed are higher as compared to the filaments taken from normal plants. This phenomenon point to higher micro rigidity of wilt-affected plants."}
{"id": "PMID:223659", "title": "[Prolonged afterglow of microorganisms].", "content": "The afterglow of some organisms is registered in the region of 460--540 nm at excitation in the 365 nm region. Apparently this effect is due to NAD and flavin containing coferments of proteins. The afterflow of NAD and riboflavin is also registered in thin films of albumin at excitation in 365 nm. The afterflow of NAD and riboflavin in thin protein films is similar to that spectrum of freezedried organisms' when the concentrations of these components are close to their concentrations in the cell.", "contents": "[Prolonged afterglow of microorganisms]. The afterglow of some organisms is registered in the region of 460--540 nm at excitation in the 365 nm region. Apparently this effect is due to NAD and flavin containing coferments of proteins. The afterflow of NAD and riboflavin is also registered in thin films of albumin at excitation in 365 nm. The afterflow of NAD and riboflavin in thin protein films is similar to that spectrum of freezedried organisms' when the concentrations of these components are close to their concentrations in the cell."}
{"id": "PMID:223663", "title": "The markers of pig heart mitochondrial sub-fractions : I. - The dual location of NADPH-cytochrome c reductase in outer membrane and microsomes.", "content": "Evidence is presented about the dual location of NADPH-cytochrome c reductase in mitochondrial outer membranes as well as in microsomes, from pig heart. A high specific activity, was found in both fractions, even after their purification by washing, digitonin treatments, or passages on sucrose gradients. A large fraction of the total activity was associated with both mitochondria and microsomes. Mitochondrial outer membrane differs from microsomes by a low choline phosphotransferase activity and the absence of cytochrome P-450. The properties of mitochondrial and microsomal rotenone-insensitive NADH- and NADPH-cytochrome c reductases were studied. In microsomes, both activities have the same optimum pH (8.5) ; in contrast, in mitochondria they have a different one. The Km-NADPH were always much higher than those for NADH. In mitochondria the Km for NAD(P)H were dependent on cytochrome c concentration. The results show that the rotenone-insensitive NADH- and NADPH-cytochrome c reductases of mitochondria and microsomes have quite different behavior and do not appear to be supported by the same enzyme.", "contents": "The markers of pig heart mitochondrial sub-fractions : I. - The dual location of NADPH-cytochrome c reductase in outer membrane and microsomes. Evidence is presented about the dual location of NADPH-cytochrome c reductase in mitochondrial outer membranes as well as in microsomes, from pig heart. A high specific activity, was found in both fractions, even after their purification by washing, digitonin treatments, or passages on sucrose gradients. A large fraction of the total activity was associated with both mitochondria and microsomes. Mitochondrial outer membrane differs from microsomes by a low choline phosphotransferase activity and the absence of cytochrome P-450. The properties of mitochondrial and microsomal rotenone-insensitive NADH- and NADPH-cytochrome c reductases were studied. In microsomes, both activities have the same optimum pH (8.5) ; in contrast, in mitochondria they have a different one. The Km-NADPH were always much higher than those for NADH. In mitochondria the Km for NAD(P)H were dependent on cytochrome c concentration. The results show that the rotenone-insensitive NADH- and NADPH-cytochrome c reductases of mitochondria and microsomes have quite different behavior and do not appear to be supported by the same enzyme."}
{"id": "PMID:223665", "title": "[Presence of enzymes catalyzing UDP-glucose biosynthesis in a low density Golgi fractions of cat hepatocytes].", "content": "A Golgi-rich fraction is prepared from cat hepatocytes by the means of a four-step sucrose density gradient. The material applied to this gradient is composed either of smooth microsomes prepared from healthy animals, or of total microsomes prepared from cat treated by 50 per cent ethanol (0.6 g/100 g body weight, administered by stomach tube). A light fraction (d : 1.10) is obtained by the two procedures. It does not show any glucose-6-phosphatase activity, but is enriched in sialyltransferase, known as a marker enzyme for Golgi apparatus. It also contains the three enzymes implicated in the biosynthetic pathway for UDP-glucose (glucokinase, phosphoglucomutase and UTP : glucose-1-phosphate uridylyltransferase). UDP-glucose being the ultimate substrate in membranous glucosylation reactions, these results could support the hypothesis that sugar-nucleotides necessary for the glycoprotein biosynthesis are produced in the Golgi vesicles directly.", "contents": "[Presence of enzymes catalyzing UDP-glucose biosynthesis in a low density Golgi fractions of cat hepatocytes]. A Golgi-rich fraction is prepared from cat hepatocytes by the means of a four-step sucrose density gradient. The material applied to this gradient is composed either of smooth microsomes prepared from healthy animals, or of total microsomes prepared from cat treated by 50 per cent ethanol (0.6 g/100 g body weight, administered by stomach tube). A light fraction (d : 1.10) is obtained by the two procedures. It does not show any glucose-6-phosphatase activity, but is enriched in sialyltransferase, known as a marker enzyme for Golgi apparatus. It also contains the three enzymes implicated in the biosynthetic pathway for UDP-glucose (glucokinase, phosphoglucomutase and UTP : glucose-1-phosphate uridylyltransferase). UDP-glucose being the ultimate substrate in membranous glucosylation reactions, these results could support the hypothesis that sugar-nucleotides necessary for the glycoprotein biosynthesis are produced in the Golgi vesicles directly."}
{"id": "PMID:223668", "title": "[Cardiotropic effects of luliberin. Interaction with rat heart sarcolemmal membrane].", "content": "Studies of the effects of luliberin (luteinizing hormone-releasing hormone) on cardiac cells showed that the hormone is specifically bound by the sarcolemmal membrane. The activity of the membrane enzyme -- reception of luliberin involves two types of binding sites with high (K' = 10(7) M-1) and low (K'' = 10(5) M-1) affinities for the hormone, respectively. The hormone has no effect on the activities of adenylate cyclase and phosphodiesterase.", "contents": "[Cardiotropic effects of luliberin. Interaction with rat heart sarcolemmal membrane]. Studies of the effects of luliberin (luteinizing hormone-releasing hormone) on cardiac cells showed that the hormone is specifically bound by the sarcolemmal membrane. The activity of the membrane enzyme -- reception of luliberin involves two types of binding sites with high (K' = 10(7) M-1) and low (K'' = 10(5) M-1) affinities for the hormone, respectively. The hormone has no effect on the activities of adenylate cyclase and phosphodiesterase."}
{"id": "PMID:223669", "title": "[Study of regulatory properties of creatine kinase from white muscles of fishes].", "content": "The kinetic and regulatory properties of creatine kinase from Silurus glanis L. white muscles were studied. The effects of several glycolytic intermediates, AMP and pyrophosphate on the creatine kinase reaction catalyzed by fresh and aged enzyme preparations were studied. Glucose-6-phosphate, fructose-1,6-diphosphate, phosphoenolpyruvated and AMP were shown to inhibit the creatine kinase reaction, increasing the cooperativity of the substrate binding. Pyrophosphate exerted a two-phase effect (activation and inhibition) in case of fresh enzyme preparations and one-phase effect (inhibition) in case of aged ones.", "contents": "[Study of regulatory properties of creatine kinase from white muscles of fishes]. The kinetic and regulatory properties of creatine kinase from Silurus glanis L. white muscles were studied. The effects of several glycolytic intermediates, AMP and pyrophosphate on the creatine kinase reaction catalyzed by fresh and aged enzyme preparations were studied. Glucose-6-phosphate, fructose-1,6-diphosphate, phosphoenolpyruvated and AMP were shown to inhibit the creatine kinase reaction, increasing the cooperativity of the substrate binding. Pyrophosphate exerted a two-phase effect (activation and inhibition) in case of fresh enzyme preparations and one-phase effect (inhibition) in case of aged ones."}
{"id": "PMID:223670", "title": "[Study of lipid dependence of glucose-6-phosphatase from rat liver and hepatoma using lipid exchange proteins].", "content": "In order to study the lipid dependence of glucose-6-phosphatase the lipid composition of microsomes from rat liver and hepatoma was modified using lipid exchange proteins. It was shown that the enzyme activity depends on the presence of phosphatidyl ethanolamine and phosphatidyl serine, but is unaffected by the enrichment of the microsomes with phosphatidyl choline. On the basis of the data obtained it was assumed that the aminophospholipids are required for the functioning of the protein carrier; however, they do not affect the activity of the catalytic component of the glucose-6-phosphatase system on the inner surface of the microsomal membrane.", "contents": "[Study of lipid dependence of glucose-6-phosphatase from rat liver and hepatoma using lipid exchange proteins]. In order to study the lipid dependence of glucose-6-phosphatase the lipid composition of microsomes from rat liver and hepatoma was modified using lipid exchange proteins. It was shown that the enzyme activity depends on the presence of phosphatidyl ethanolamine and phosphatidyl serine, but is unaffected by the enrichment of the microsomes with phosphatidyl choline. On the basis of the data obtained it was assumed that the aminophospholipids are required for the functioning of the protein carrier; however, they do not affect the activity of the catalytic component of the glucose-6-phosphatase system on the inner surface of the microsomal membrane."}
{"id": "PMID:223667", "title": "Formation and destruction of photoinduced paramagnetic centers in melanin-containing fungi.", "content": "Irradiation of the melanin-containing fungi Cladosporium transchelii, its pigmented mutants, Stemphyllium ilicis, Oidiodendron cerealis, and isolated melanin pigment with UV or visible light leads to an increase in the concentration of paramagnetic centers (PC) in melanin pigments, recorded by the EPR technique. Differences were established in the reaction of melanin of UV-sensitive and UV-resistant cultures to illumination. Paramagnetic centers are generated by a single-quantum mechanism (light with lambda less than 900 nm was active). A mechanism is proposed for processes occurring during illumination of dark-pigmented subjects, which includes photoinduced electron transport in melanin and dark recombination of the PC formed in the process.", "contents": "Formation and destruction of photoinduced paramagnetic centers in melanin-containing fungi. Irradiation of the melanin-containing fungi Cladosporium transchelii, its pigmented mutants, Stemphyllium ilicis, Oidiodendron cerealis, and isolated melanin pigment with UV or visible light leads to an increase in the concentration of paramagnetic centers (PC) in melanin pigments, recorded by the EPR technique. Differences were established in the reaction of melanin of UV-sensitive and UV-resistant cultures to illumination. Paramagnetic centers are generated by a single-quantum mechanism (light with lambda less than 900 nm was active). A mechanism is proposed for processes occurring during illumination of dark-pigmented subjects, which includes photoinduced electron transport in melanin and dark recombination of the PC formed in the process."}
{"id": "PMID:223671", "title": "[Nucleotide specificity of rat liver thiamine pyrophosphokinase].", "content": "The nucleotide specificity of thiamine pyrophosphokinase from rat liver was studied. The enzyme was found to possess a sufficiently wide substrate specificity. Any of the nucleotides can be a donor of the pyrophosphate groups for TDP biosynthesis at two pH optima of the enzyme in the T-kinase reaction under the Mg2++/NTP optimal ratio. The minimal requirement for the substrate structure allowing to predict the position of the split nucleotide phosphoester bond was postulated.", "contents": "[Nucleotide specificity of rat liver thiamine pyrophosphokinase]. The nucleotide specificity of thiamine pyrophosphokinase from rat liver was studied. The enzyme was found to possess a sufficiently wide substrate specificity. Any of the nucleotides can be a donor of the pyrophosphate groups for TDP biosynthesis at two pH optima of the enzyme in the T-kinase reaction under the Mg2++/NTP optimal ratio. The minimal requirement for the substrate structure allowing to predict the position of the split nucleotide phosphoester bond was postulated."}
{"id": "PMID:223672", "title": "[Some properties of partially purified preparations of cAMP phosphodiesterase from beef heart].", "content": "Beef heart cAMP phosphodiesterase (EC 3.1.4.17) was isolated and partially purified using fractionation by ammonium sulfate and gel filtration on the columns with Sephadex G-200 and Sepharose 6B. This method allowed to preserve the enzyme binding to the low-molecular weight thermostable protein regulator of the phosphodiesterase activity. The enzyme preparation was purified 130--180-fold as compared to the original homogenate. The pH-dependence of the enzyme activity in the imidazole and tris -- buffers for the fraction with maximal activity was carried out. The kinetic analysis of this fraction revealed an abnormal kinetic behaviour with two Km values. The enzyme is represented by four forms differing in their molecular weights and possessing different capacity for activation by Ca2+ and protein regulator. No activation was observed in the forms with higher molecular weights, whereas the activity of the forms with lower molecular weights depended on the presence of Ca2+ and protein regulator. It is assumed that some of the above-described forms are capable of interconversions.", "contents": "[Some properties of partially purified preparations of cAMP phosphodiesterase from beef heart]. Beef heart cAMP phosphodiesterase (EC 3.1.4.17) was isolated and partially purified using fractionation by ammonium sulfate and gel filtration on the columns with Sephadex G-200 and Sepharose 6B. This method allowed to preserve the enzyme binding to the low-molecular weight thermostable protein regulator of the phosphodiesterase activity. The enzyme preparation was purified 130--180-fold as compared to the original homogenate. The pH-dependence of the enzyme activity in the imidazole and tris -- buffers for the fraction with maximal activity was carried out. The kinetic analysis of this fraction revealed an abnormal kinetic behaviour with two Km values. The enzyme is represented by four forms differing in their molecular weights and possessing different capacity for activation by Ca2+ and protein regulator. No activation was observed in the forms with higher molecular weights, whereas the activity of the forms with lower molecular weights depended on the presence of Ca2+ and protein regulator. It is assumed that some of the above-described forms are capable of interconversions."}
{"id": "PMID:223673", "title": "[Photochemical and spectral properies of the photosystem I reaction centers-enriched particles].", "content": "The photosystem I reaction centers-enriched particles (RCP) having the ratio of P700/chlorophyll of 1 : 20--1 :30 were prepared from stroma lamellae photosystem subchloroplast fragments by extraction with water-saturated ether. The EPR signals and light-induced absorption changes indicate that the reaction centers are active in the particles. The spectral properties of the RCP were characterized. The main red absorption maximum is located at 673--674 nm with a \"shoulder\" at about 684--688 nm. A comparative analysis of the subchloroplast fragments and RCP absorption and fluorescence spectra suggests that the chl. a forms absorbed in the region of 680--695 nm are more closely associated with the reaction center. The most long-wavelength absorbing chl. a forms with maxima around 730--740 nm in the low temperature fluorescence spectra were not found in the RCP.", "contents": "[Photochemical and spectral properies of the photosystem I reaction centers-enriched particles]. The photosystem I reaction centers-enriched particles (RCP) having the ratio of P700/chlorophyll of 1 : 20--1 :30 were prepared from stroma lamellae photosystem subchloroplast fragments by extraction with water-saturated ether. The EPR signals and light-induced absorption changes indicate that the reaction centers are active in the particles. The spectral properties of the RCP were characterized. The main red absorption maximum is located at 673--674 nm with a \"shoulder\" at about 684--688 nm. A comparative analysis of the subchloroplast fragments and RCP absorption and fluorescence spectra suggests that the chl. a forms absorbed in the region of 680--695 nm are more closely associated with the reaction center. The most long-wavelength absorbing chl. a forms with maxima around 730--740 nm in the low temperature fluorescence spectra were not found in the RCP."}
{"id": "PMID:223674", "title": "[Effects of the medium on the rate of electron transfer in a reconstituted system of mitochondrial hydroxylation].", "content": "Effects of ionic strength, pH, viscosity, concentrations of components and nature of acceptor on the rate of NADPH oxidation and acceptor reduction were studied in a hydroxylation system containing adrenodoxin reductase, adrenodoxin and cytochrome P450 or cytochrome c. The maximal rate was observed with 0.05--0.10 M phosphate buffer, pH 6.0--6.5 and at the adrenoxin/flavoprotein/cytochrome ratio of 1 : 1 : 1. The electron transfer rate was decreased with an increase in viscosity. Cytochrome P450 is more efficient as a terminal acceptor as compared to cytochrome c or indigodisulphonate.", "contents": "[Effects of the medium on the rate of electron transfer in a reconstituted system of mitochondrial hydroxylation]. Effects of ionic strength, pH, viscosity, concentrations of components and nature of acceptor on the rate of NADPH oxidation and acceptor reduction were studied in a hydroxylation system containing adrenodoxin reductase, adrenodoxin and cytochrome P450 or cytochrome c. The maximal rate was observed with 0.05--0.10 M phosphate buffer, pH 6.0--6.5 and at the adrenoxin/flavoprotein/cytochrome ratio of 1 : 1 : 1. The electron transfer rate was decreased with an increase in viscosity. Cytochrome P450 is more efficient as a terminal acceptor as compared to cytochrome c or indigodisulphonate."}
{"id": "PMID:223675", "title": "[Role of lipids in regulation of microsomal glucose-6-phosphatase activity after modification of mcirosomes in vivo and in vitro. Effect of phospholipid effectors on the activity of glucose-6-phosphatase].", "content": "Modification of microsomal membranes in vivo and in vitro results in changes of the glucose-6-phosphate and inorganic pyrophosphate phosphohydrolase activities of liver microsomal glucose-6-phosphate phosphohydrolase (EC 3.1.3.9). It was demonstrated that the glucose-6-phosphate phosphohydrolase activity of glucose-6-phosphatase depends on the content of phosphatidylethanolamine in the microsomal membranes, whereas the inorganic pyrophosphate phosphohydrolase activity seems to be dependent on the phosphatidylserine content. It is assumed that the regulation of the corresponding enzyme activities by these phospholipids is performed by the same allosteric mechanism in vitro and in vivo.", "contents": "[Role of lipids in regulation of microsomal glucose-6-phosphatase activity after modification of mcirosomes in vivo and in vitro. Effect of phospholipid effectors on the activity of glucose-6-phosphatase]. Modification of microsomal membranes in vivo and in vitro results in changes of the glucose-6-phosphate and inorganic pyrophosphate phosphohydrolase activities of liver microsomal glucose-6-phosphate phosphohydrolase (EC 3.1.3.9). It was demonstrated that the glucose-6-phosphate phosphohydrolase activity of glucose-6-phosphatase depends on the content of phosphatidylethanolamine in the microsomal membranes, whereas the inorganic pyrophosphate phosphohydrolase activity seems to be dependent on the phosphatidylserine content. It is assumed that the regulation of the corresponding enzyme activities by these phospholipids is performed by the same allosteric mechanism in vitro and in vivo."}
{"id": "PMID:223676", "title": "[Regulation of alpha-ketoglutarate dehydrogenase complex from pigeon breast muscle].", "content": "The activity of alpha-ketoglutarate dehydrogenase complex from pigeon breast muscle is controlled by ADP and the reaction products, i. e. succinyl-CoA and NADH. ADP activates the alpha-ketoglutarate dehydrogenase component of the complex, whereas NADH inhibits alpha-ketoglutarate dehydrogenase and lipoyl dehydrogenase. In the presence of NADH the kinetic curve of the complex with respect to alpha-ketoglutarate and NAD and the dependence of upsilon versus [NAD] and upsilon versus [Lip (SH)2] in the lipoyl dehydrogenase reaction are S-shaped. In the absence of inhibitor ADP had no activating effect on lipoyl dehydrogenase; however, in the presence of NADH ADP decreases the cooperativity for NAD. The cooperative kinetics of the constituent enzymes of the complex are indicative of its allosteric properties. Isolation of the alpha-ketoglutarate dehydrogenase complex and its lipoyl dehydrogenase and alpha-ketoglutarate dehydrogenase components in a desensitized state confirms their allosteric nature. It is assumed that NADH effects of isolated alpha-ketoglutarate dehydrogenase is due to a shift in the equilibrium between different oligomeric forms of the enzyme.", "contents": "[Regulation of alpha-ketoglutarate dehydrogenase complex from pigeon breast muscle]. The activity of alpha-ketoglutarate dehydrogenase complex from pigeon breast muscle is controlled by ADP and the reaction products, i. e. succinyl-CoA and NADH. ADP activates the alpha-ketoglutarate dehydrogenase component of the complex, whereas NADH inhibits alpha-ketoglutarate dehydrogenase and lipoyl dehydrogenase. In the presence of NADH the kinetic curve of the complex with respect to alpha-ketoglutarate and NAD and the dependence of upsilon versus [NAD] and upsilon versus [Lip (SH)2] in the lipoyl dehydrogenase reaction are S-shaped. In the absence of inhibitor ADP had no activating effect on lipoyl dehydrogenase; however, in the presence of NADH ADP decreases the cooperativity for NAD. The cooperative kinetics of the constituent enzymes of the complex are indicative of its allosteric properties. Isolation of the alpha-ketoglutarate dehydrogenase complex and its lipoyl dehydrogenase and alpha-ketoglutarate dehydrogenase components in a desensitized state confirms their allosteric nature. It is assumed that NADH effects of isolated alpha-ketoglutarate dehydrogenase is due to a shift in the equilibrium between different oligomeric forms of the enzyme."}
{"id": "PMID:223678", "title": "Endorphin-locus coeruleus connection mediates opiate action and withdrawal.", "content": "Endorphins and exogenous opiates inhibit the activity of the noradrenergic nucleus locus coeruleus (LC). This discovery of endorphin transmitters and their interaction with the LC has supported our studies which have suggested that the majority of the signs and symptoms of opiate withdrawal are mimicked by electrical or chemical activation of the LC. We hypothesize that this endorphin-LC connection is critical to opiate action and the withdrawal syndrome. This hypothesis suggests that chronic opiate administration inhibits LC activity and that opiate abstinence after addiction results in a release from inhibition with resultant LC hyperactivity. This hypothesis is supported by recent data suggesting that clonidine as a drug which inhibits the LC and LC-mediated noradrenergic activation, is an efficacious non-opiate treatment for opiate withdrawal. This hypothesis can be tested in man by evaluating drugs which inhibit the LC and LC-mediated behaviors for anti-withdrawal efficacy.", "contents": "Endorphin-locus coeruleus connection mediates opiate action and withdrawal. Endorphins and exogenous opiates inhibit the activity of the noradrenergic nucleus locus coeruleus (LC). This discovery of endorphin transmitters and their interaction with the LC has supported our studies which have suggested that the majority of the signs and symptoms of opiate withdrawal are mimicked by electrical or chemical activation of the LC. We hypothesize that this endorphin-LC connection is critical to opiate action and the withdrawal syndrome. This hypothesis suggests that chronic opiate administration inhibits LC activity and that opiate abstinence after addiction results in a release from inhibition with resultant LC hyperactivity. This hypothesis is supported by recent data suggesting that clonidine as a drug which inhibits the LC and LC-mediated noradrenergic activation, is an efficacious non-opiate treatment for opiate withdrawal. This hypothesis can be tested in man by evaluating drugs which inhibit the LC and LC-mediated behaviors for anti-withdrawal efficacy."}
{"id": "PMID:223680", "title": "Erythrocyte membrane protein kinase and adenylate cyclase in Duchenne muscular dystrophy.", "content": "In freshly prepared erythrocyte membranes from normal individuals and patients with Duchenne progressive muscular dystrophy the endogenous protein kinase and the cAMP stimulated phosphorylation was identical for the 3 main32P proteins including spectrin (protein band II). Another enzyme, adenylate cyclase, was found unchanged. Altered protein kinase and adenylate cyclase have been reported in this disorder. We have no explanation for these discrepancies.", "contents": "Erythrocyte membrane protein kinase and adenylate cyclase in Duchenne muscular dystrophy. In freshly prepared erythrocyte membranes from normal individuals and patients with Duchenne progressive muscular dystrophy the endogenous protein kinase and the cAMP stimulated phosphorylation was identical for the 3 main32P proteins including spectrin (protein band II). Another enzyme, adenylate cyclase, was found unchanged. Altered protein kinase and adenylate cyclase have been reported in this disorder. We have no explanation for these discrepancies."}
{"id": "PMID:223681", "title": "Evidence that eel acetylcholinesterase is not an integral membrane protein.", "content": "Detergent binding studies indicated that the neural enzyme, acetylcholinesterase, did not exhibit the properties of an integral membrane protein. The 11S form was isolated by affinity chromatography from a tryptic digest and the 14S and 18S forms in like manner from an undigested preparation. Studies were performed with [3H]TX-100 to determine the extent of binding by these forms and with catalase and human low density lipoprotein as reference proteins. All forms of the enzyme bound less than 0.04 mg TX-100/mg protein which is only slightly higher than binding by catalase and about 25 fold lower than the binding exhibited by low density lipoprotein.", "contents": "Evidence that eel acetylcholinesterase is not an integral membrane protein. Detergent binding studies indicated that the neural enzyme, acetylcholinesterase, did not exhibit the properties of an integral membrane protein. The 11S form was isolated by affinity chromatography from a tryptic digest and the 14S and 18S forms in like manner from an undigested preparation. Studies were performed with [3H]TX-100 to determine the extent of binding by these forms and with catalase and human low density lipoprotein as reference proteins. All forms of the enzyme bound less than 0.04 mg TX-100/mg protein which is only slightly higher than binding by catalase and about 25 fold lower than the binding exhibited by low density lipoprotein."}
{"id": "PMID:223683", "title": "[Effect of heparin, spermidine and Be2+ ions on the phosphatase and RNAse activity of rat liver cell nuclei].", "content": "Effects of heparin, spermidine, and Be2+ ions on the ATPase and beta-glycerophosphatase and RNA-ase activities of the rat liver cell nuclei were studied. Be2+ was shown to inhibit the ATPase activity and, to a lesser extent, beta-glycerophosphatase activities. Physiological concentrations of heparin and spermidine also lowered the mentioned two activities, as well as the RNAase activity of the nuclei. Evidence is presented for the inhibitory effect of heparin and spermidine on endonucleases.", "contents": "[Effect of heparin, spermidine and Be2+ ions on the phosphatase and RNAse activity of rat liver cell nuclei]. Effects of heparin, spermidine, and Be2+ ions on the ATPase and beta-glycerophosphatase and RNA-ase activities of the rat liver cell nuclei were studied. Be2+ was shown to inhibit the ATPase activity and, to a lesser extent, beta-glycerophosphatase activities. Physiological concentrations of heparin and spermidine also lowered the mentioned two activities, as well as the RNAase activity of the nuclei. Evidence is presented for the inhibitory effect of heparin and spermidine on endonucleases."}
{"id": "PMID:223684", "title": "[Change in the activity of the key gluconeogenesis enzymes in the rat liver and kidneys during the action of subextreme and extreme factors on the body].", "content": "The activity of glucogenesis key enzymes (phosphoenolpyruvate carboxinase, fructoso-1,6-siphosphatase, glucoso-6-phosphatase) of the rat liver and kidneys was studied simultaneously under the effect of extreme and subextreme factors on the organism. The low initial phosphoenolpyruvate carboxikinase activity in the liver and its high inductivity under extreme conditions suggest a role of this enzyme as limiting link in glyconeogenesis. The activity of phosphoenolpyruvate carboxinase in the kidneys is comparable to that of fructoso-1,6-diphosphatase; it is considerably higher than the activity of glucoso-6-phosphatase. The phosphoenolpyruvate carboxinase activity in the kidneys is 5--6 times higher than in the liver. The activity of phosphoenolpyruvate carboxinase and glucoso-6-phosphatase is increased under the effect of extreme factors, and that of fructoso-1,6-diphosphatase remains unchanged. The lack of clear synchronous changes in the activity of glucogenesis key enzymes in the liver and kidneys indicates that the cells of these organs do not provide the united operon for phosphoenolpyruvate carboxinase, fructoso-1,6-diphosphatase and glucoso-6-phosphatase with common regulation mechanism.", "contents": "[Change in the activity of the key gluconeogenesis enzymes in the rat liver and kidneys during the action of subextreme and extreme factors on the body]. The activity of glucogenesis key enzymes (phosphoenolpyruvate carboxinase, fructoso-1,6-siphosphatase, glucoso-6-phosphatase) of the rat liver and kidneys was studied simultaneously under the effect of extreme and subextreme factors on the organism. The low initial phosphoenolpyruvate carboxikinase activity in the liver and its high inductivity under extreme conditions suggest a role of this enzyme as limiting link in glyconeogenesis. The activity of phosphoenolpyruvate carboxinase in the kidneys is comparable to that of fructoso-1,6-diphosphatase; it is considerably higher than the activity of glucoso-6-phosphatase. The phosphoenolpyruvate carboxinase activity in the kidneys is 5--6 times higher than in the liver. The activity of phosphoenolpyruvate carboxinase and glucoso-6-phosphatase is increased under the effect of extreme factors, and that of fructoso-1,6-diphosphatase remains unchanged. The lack of clear synchronous changes in the activity of glucogenesis key enzymes in the liver and kidneys indicates that the cells of these organs do not provide the united operon for phosphoenolpyruvate carboxinase, fructoso-1,6-diphosphatase and glucoso-6-phosphatase with common regulation mechanism."}
{"id": "PMID:223685", "title": "[Effect of leucine-enkephalin on the interneuronal transmission of excitation].", "content": "In the experiments on non-anesthetized flaxedil-immobilized cats it has been shown that the injection of leucin-enkephalin (1 mg) into the lateral ventricle of the brain is followed by the inhibition of evoked potentials in the ventrolateral columns of the spinal cord and of segmental interneuronal transmission in the spinal cord as well as by the reduction of the amplitude of potentials in the S I zone of the brain cortex induced by the sciatic nerve stimulation. Naloxone (1 mg/kg, i.v.) prevented the effects of leucin-enkephalin. Methysergide pretreatment (2.5 mg/kg, i.p.) led to a decrease of leucin-enkephalin effect on the interneuronal transmission in the spinal cord. Leucin-enkephalin failed to change the amplitude of polysynaptic potentials of glosso-mandibular reflex integrated at the brain stem level.", "contents": "[Effect of leucine-enkephalin on the interneuronal transmission of excitation]. In the experiments on non-anesthetized flaxedil-immobilized cats it has been shown that the injection of leucin-enkephalin (1 mg) into the lateral ventricle of the brain is followed by the inhibition of evoked potentials in the ventrolateral columns of the spinal cord and of segmental interneuronal transmission in the spinal cord as well as by the reduction of the amplitude of potentials in the S I zone of the brain cortex induced by the sciatic nerve stimulation. Naloxone (1 mg/kg, i.v.) prevented the effects of leucin-enkephalin. Methysergide pretreatment (2.5 mg/kg, i.p.) led to a decrease of leucin-enkephalin effect on the interneuronal transmission in the spinal cord. Leucin-enkephalin failed to change the amplitude of polysynaptic potentials of glosso-mandibular reflex integrated at the brain stem level."}
{"id": "PMID:223686", "title": "[Dynamics of the change in cyclic nucleotide content in wound tissues].", "content": "Changes in the content of cyclic nucleotides (cAMP and cGMP) in the wound tissues (muscles and granulations) were studied in experiments on rats. A wound with skin defect in the dorsal area with a crushed underlying muscle served as an experimental model. It was shown that the cAMP content in the muscular tissue rises twice: during the 1st day and to a greater measure on the 7th day. The cGMP content slightly increases on the 1-4th day, drops on the 7th day and increases cAMP concentration changes similarly to that inthe muscular tissue: it increases on the 7th day and drops on the 14th day. On the contrary, the cGMP content curve in granulations is more monotonous, only a slight increase being observed on the 7th day.", "contents": "[Dynamics of the change in cyclic nucleotide content in wound tissues]. Changes in the content of cyclic nucleotides (cAMP and cGMP) in the wound tissues (muscles and granulations) were studied in experiments on rats. A wound with skin defect in the dorsal area with a crushed underlying muscle served as an experimental model. It was shown that the cAMP content in the muscular tissue rises twice: during the 1st day and to a greater measure on the 7th day. The cGMP content slightly increases on the 1-4th day, drops on the 7th day and increases cAMP concentration changes similarly to that inthe muscular tissue: it increases on the 7th day and drops on the 14th day. On the contrary, the cGMP content curve in granulations is more monotonous, only a slight increase being observed on the 7th day."}
{"id": "PMID:223687", "title": "[Increased sensitivity of the fatty tissue of rats with spontaneous hypertension to the action of ACTH. The role of calcium].", "content": "The action of ACTH on the adipose tissue lypolysis was studied in rats with spontaneous and renal hypertension as well as in normotensive rats of the respective control groups. It was demonstrated that sensitivity of the adipose tissue SHR to ACTH was increased as compared to normotensive controls. The data presented indicate that the increased sensitivity is due to the state or content of intracellular calcium. The rats with renal hypertension did not show such an increased sensitivity of the adipose tissue to ACTH.", "contents": "[Increased sensitivity of the fatty tissue of rats with spontaneous hypertension to the action of ACTH. The role of calcium]. The action of ACTH on the adipose tissue lypolysis was studied in rats with spontaneous and renal hypertension as well as in normotensive rats of the respective control groups. It was demonstrated that sensitivity of the adipose tissue SHR to ACTH was increased as compared to normotensive controls. The data presented indicate that the increased sensitivity is due to the state or content of intracellular calcium. The rats with renal hypertension did not show such an increased sensitivity of the adipose tissue to ACTH."}
{"id": "PMID:223688", "title": "[Bradykinin as a factor regulating synaptic inflow to the neurons in Helix pomata].", "content": "The action of bradykinin on spontaneous electric activity of Helix pomata neurones from the subfaringeal complex was studied by microionophoresis. Bradykinin not only facilitates the neuronal responses to synaptic activation, but also prolongs the activation-induced generation of the potential action. Bradykinin effects were observed only in experiments conducted in spring.", "contents": "[Bradykinin as a factor regulating synaptic inflow to the neurons in Helix pomata]. The action of bradykinin on spontaneous electric activity of Helix pomata neurones from the subfaringeal complex was studied by microionophoresis. Bradykinin not only facilitates the neuronal responses to synaptic activation, but also prolongs the activation-induced generation of the potential action. Bradykinin effects were observed only in experiments conducted in spring."}
{"id": "PMID:223689", "title": "[Carbohydrate metabolism enzymatic activity and its alteration under the influence of thyroid hormone during tumor growth].", "content": "The activity of hexokinase (HK), its isoenzymes, glucose-6-phosphatase and glucose-6-phosphate dehydrogenase, and the triiodothyronine (T3) effect on this activity in the liver tissue of mice bearing transplantable hepatoma 22a were studied in different periods of the tumor growtn. It was shown that alterations in the activity of the enzymes in the liver of tumor-bearing mice occurred already in the presence of a small tumor. More profound alterations in the activity of all enzymes studied, apart from those in the enzymatic pattern of HK, could be observed starting from day 21after the tumor transplantation. In the initial stages of the hepatoma growth the activity of the test enzymes in the liver was regulated by thyroid hormone. The effect of Ta on the activity of the enzymes in the host liver was gradually lost in the course of the tumor growth.", "contents": "[Carbohydrate metabolism enzymatic activity and its alteration under the influence of thyroid hormone during tumor growth]. The activity of hexokinase (HK), its isoenzymes, glucose-6-phosphatase and glucose-6-phosphate dehydrogenase, and the triiodothyronine (T3) effect on this activity in the liver tissue of mice bearing transplantable hepatoma 22a were studied in different periods of the tumor growtn. It was shown that alterations in the activity of the enzymes in the liver of tumor-bearing mice occurred already in the presence of a small tumor. More profound alterations in the activity of all enzymes studied, apart from those in the enzymatic pattern of HK, could be observed starting from day 21after the tumor transplantation. In the initial stages of the hepatoma growth the activity of the test enzymes in the liver was regulated by thyroid hormone. The effect of Ta on the activity of the enzymes in the host liver was gradually lost in the course of the tumor growth."}
{"id": "PMID:223690", "title": "[Participation of thyroid hormones in the regulation of the genetic activity of normal and transformed human cells].", "content": "It is shown that 125J-thyroid hormones are localized on the structures of the interphasic nucleus and metaphasic chromosomes of cultured fibroblasts of 8--10-day human embryos. At the same time, the labelled thyroid hormones, though localizing in the interphasic nuclei of HeLa cells, are not accepted, unlike normal cells, by their metaphasic chromosomes. It is suggested that during transformation the acceptor ares of the HeLa cells genome lost their property to bind their own receptor complexes with thyroid hormones.", "contents": "[Participation of thyroid hormones in the regulation of the genetic activity of normal and transformed human cells]. It is shown that 125J-thyroid hormones are localized on the structures of the interphasic nucleus and metaphasic chromosomes of cultured fibroblasts of 8--10-day human embryos. At the same time, the labelled thyroid hormones, though localizing in the interphasic nuclei of HeLa cells, are not accepted, unlike normal cells, by their metaphasic chromosomes. It is suggested that during transformation the acceptor ares of the HeLa cells genome lost their property to bind their own receptor complexes with thyroid hormones."}
{"id": "PMID:223691", "title": "[Characteristics of the effect of estradiol on prolactin secretion by adenohyophyseal cells from intact and ovariectomized rats in primary monolayer cultures].", "content": "Estradiol directly stimulated the secretion of prolactin by the adenohypophyseal cells of intact rats in a monolayer culture. Complex interactions between estradiol and some other regulators of the hypophyseal lactotropic function were revealed. It was established that changes in prolactin synthesis and secretion in ovariectomized rats persisted for 3--4 days of adenohypophyseal cell cultivation in vitro.", "contents": "[Characteristics of the effect of estradiol on prolactin secretion by adenohyophyseal cells from intact and ovariectomized rats in primary monolayer cultures]. Estradiol directly stimulated the secretion of prolactin by the adenohypophyseal cells of intact rats in a monolayer culture. Complex interactions between estradiol and some other regulators of the hypophyseal lactotropic function were revealed. It was established that changes in prolactin synthesis and secretion in ovariectomized rats persisted for 3--4 days of adenohypophyseal cell cultivation in vitro."}
{"id": "PMID:223692", "title": "Estimation of kinetic parameters of neutrophilic, eosinophilic, and basophilic granulocytes in human blood.", "content": "Two hematologically normal patients with glioblastoma and six patients with chronic lymphocytic leukemia received continuous 3H-thymidine infusions for 3--10 days. In autoradiographs of blood cell smears taken for 25 days or more after the beginning of 3H-thymidine administration the labeling index and the labeling intensity of granulocytes were determined. A sufficiently high labeling intensity, i.e. a sufficiently long autoradiographic exposure time was found to be critical for obtaining valid and reproducible results. On the basis of certain assumptions discussed in detail, complete labeling of cells with 3H-thymidine followed by autoradiographic evaluation and mathematical analysis of the labeling patterns seems to be a suitable method for estimation of kinetic parameters of postmitotic granulocytes in vivo. The mean intramedullary maturation and storage time was observed to be 115 +/- 7 h or neutrophils, 103 +/- 4 h for eosinophils and 103 +/- 11 h for basophils. The mean relative inflow rate into the blood (or relative turnover rate in the blood) was found to be 4.2 +/- 0.4/h for neutrophils, 4.0 +/- 0.4%/h for eosinophils and 1.2 +/- 0.3%/h for basophils. The mean blood transit time (or blood sojourn time) was estimated to be 25 +/- 2 h or neutrophils, 26 +/- 3 h for eosinophils and 89 +/- 21 h for basophils. Accordingly the half lifes (T 1/2) of granulocytes in the blood were 17.3 +/- 1.4 h for neutrophils, 18.0 +/- 2.1 for eosinophils and 62 +/- 15 h for basophils. Under the quasi steady state conditions of this study the kinetics of granulocytes in the present CLL patients appeared to be normal, despite a marked lymphocytic infiltration of the bone marrow. The apparent discrepancy between these findings and the data obtained with autotransfusion of DFP-labeled granulocytes is discussed.", "contents": "Estimation of kinetic parameters of neutrophilic, eosinophilic, and basophilic granulocytes in human blood. Two hematologically normal patients with glioblastoma and six patients with chronic lymphocytic leukemia received continuous 3H-thymidine infusions for 3--10 days. In autoradiographs of blood cell smears taken for 25 days or more after the beginning of 3H-thymidine administration the labeling index and the labeling intensity of granulocytes were determined. A sufficiently high labeling intensity, i.e. a sufficiently long autoradiographic exposure time was found to be critical for obtaining valid and reproducible results. On the basis of certain assumptions discussed in detail, complete labeling of cells with 3H-thymidine followed by autoradiographic evaluation and mathematical analysis of the labeling patterns seems to be a suitable method for estimation of kinetic parameters of postmitotic granulocytes in vivo. The mean intramedullary maturation and storage time was observed to be 115 +/- 7 h or neutrophils, 103 +/- 4 h for eosinophils and 103 +/- 11 h for basophils. The mean relative inflow rate into the blood (or relative turnover rate in the blood) was found to be 4.2 +/- 0.4/h for neutrophils, 4.0 +/- 0.4%/h for eosinophils and 1.2 +/- 0.3%/h for basophils. The mean blood transit time (or blood sojourn time) was estimated to be 25 +/- 2 h or neutrophils, 26 +/- 3 h for eosinophils and 89 +/- 21 h for basophils. Accordingly the half lifes (T 1/2) of granulocytes in the blood were 17.3 +/- 1.4 h for neutrophils, 18.0 +/- 2.1 for eosinophils and 62 +/- 15 h for basophils. Under the quasi steady state conditions of this study the kinetics of granulocytes in the present CLL patients appeared to be normal, despite a marked lymphocytic infiltration of the bone marrow. The apparent discrepancy between these findings and the data obtained with autotransfusion of DFP-labeled granulocytes is discussed."}
{"id": "PMID:223698", "title": "Mercuric chloride induced enzymological changes in kidney and ovary of a teleost fish, Channa punctatus.", "content": "The effect of LC(50) (1.8 MG/L) and a sublethal concentration (0.03 mg/L) of in vivo mercuric chloride exposure on the activities of acid and alkaline phosphatases, glucose-6-phosphatase, lipase and urease in the kidneys and ovaries of a teleost fish, Channa punctatus has been studied after 96 hr and 30 days respectively. It has been observed that the activities of all the enzymes except acid phosphatase were significantly inhibited in both the tissues. However, treatment for 96 hr resulted in more marked inhibition than 30 days of treatment. Acid phosphatase showed elevation in activity in the kidney after 96 hr of treatment.", "contents": "Mercuric chloride induced enzymological changes in kidney and ovary of a teleost fish, Channa punctatus. The effect of LC(50) (1.8 MG/L) and a sublethal concentration (0.03 mg/L) of in vivo mercuric chloride exposure on the activities of acid and alkaline phosphatases, glucose-6-phosphatase, lipase and urease in the kidneys and ovaries of a teleost fish, Channa punctatus has been studied after 96 hr and 30 days respectively. It has been observed that the activities of all the enzymes except acid phosphatase were significantly inhibited in both the tissues. However, treatment for 96 hr resulted in more marked inhibition than 30 days of treatment. Acid phosphatase showed elevation in activity in the kidney after 96 hr of treatment."}
{"id": "PMID:223700", "title": "Effects of lead nitrate on the activities of a few enzymes in the kidney and ovary Heteropneustes fossillis.", "content": "The effect of LC(50) and a sublethal concentration of lead nitrate on the activities of alkaline phosphatase, acid phosphatase, glucose-6-phosphatase, lipase and urease in the kidneys and ovaries of a teleost fish, Channa punctatus has been examined after 96 hr and 30 days respectively. The results show that all the five enzymes in the two tissues are inhibited significantly at both the experimental stages. However, the inhibition produced after 30 days by the sublethal concentration ish higher indicating the cumulative action of lead. Further, the inhibition of enzymes is, more marked in kidney than in the ovary.", "contents": "Effects of lead nitrate on the activities of a few enzymes in the kidney and ovary Heteropneustes fossillis. The effect of LC(50) and a sublethal concentration of lead nitrate on the activities of alkaline phosphatase, acid phosphatase, glucose-6-phosphatase, lipase and urease in the kidneys and ovaries of a teleost fish, Channa punctatus has been examined after 96 hr and 30 days respectively. The results show that all the five enzymes in the two tissues are inhibited significantly at both the experimental stages. However, the inhibition produced after 30 days by the sublethal concentration ish higher indicating the cumulative action of lead. Further, the inhibition of enzymes is, more marked in kidney than in the ovary."}
{"id": "PMID:223701", "title": "The in vivo effect of mercuric chloride on some digestive enzymes of a fresh water teleost fish, Channa punctatus.", "content": "Alterations in the activities of alkaline phosphatase, acid phosphatase, glucose-6-phosphatase amylase, trypsin, pepsin, aminotripeptidase, glycylglycine dipeptidase and carnosinase due to exposure of Channa punctatus to a sublethal concentration (0.30 mg/L) of mercuric chloride by bath for 20 days have been studied in the different parts of the digestive system. Afall in the activities of the three phosphatases was recorded except for alkaline phosphatase which showed a slight elevation in activity in intestine and pyloric caeca. An increase in the activity of amylase and the two proteases was observed in all the portions of the digestive system. The three peptidases revealed a decrease in activity.", "contents": "The in vivo effect of mercuric chloride on some digestive enzymes of a fresh water teleost fish, Channa punctatus. Alterations in the activities of alkaline phosphatase, acid phosphatase, glucose-6-phosphatase amylase, trypsin, pepsin, aminotripeptidase, glycylglycine dipeptidase and carnosinase due to exposure of Channa punctatus to a sublethal concentration (0.30 mg/L) of mercuric chloride by bath for 20 days have been studied in the different parts of the digestive system. Afall in the activities of the three phosphatases was recorded except for alkaline phosphatase which showed a slight elevation in activity in intestine and pyloric caeca. An increase in the activity of amylase and the two proteases was observed in all the portions of the digestive system. The three peptidases revealed a decrease in activity."}
{"id": "PMID:223706", "title": "The relationship between the pharmacokinetics, cholinesterase inhibition and facilitation of twitch tension of the quaternary ammonium anticholinesterase drugs, neostigmine, pyridostigmine, edrophonium and 3-hydroxyphenyltrimethylammonium.", "content": "1 The relationship between the concentration of drug in plasma, the inhibition of erythrocyte acetylcholinesterase and the facilitation of neuromuscular transmission has been studied in the rat after the administration of neostigmine, pyridostigmine, edrophonium and 3-hydroxyphenyltrimethyl-ammonium (3-OH PTMA). 2 After the administration of neostigmine or pyridostigmine, acetylcholinesterase activity recovered only slowly due to the covalent nature of the inhibition. In contrast, recovery from the reversible inhibition caused by edrophonium or 3-OH PTMA was rapid and showed a direct relationship to the plasma concentration of these drugs. 3 There was a statistically significant linear correlation between the logarithm of the plasma concentration of the drugs and the increase in the tibialis twitch tension. 4 The relationship between the inhibition of acetylcholinesterase and the facilitation of neuromuscular transmission was complex. When the enzyme was less than 85% inhibited no facilitation occurred. Between 85% and 98% inhibition, facilitation was linearly related to enzyme inhibition. Above 98% inhibition, facilitation was unrelated to inhibition of the enzyme.", "contents": "The relationship between the pharmacokinetics, cholinesterase inhibition and facilitation of twitch tension of the quaternary ammonium anticholinesterase drugs, neostigmine, pyridostigmine, edrophonium and 3-hydroxyphenyltrimethylammonium. 1 The relationship between the concentration of drug in plasma, the inhibition of erythrocyte acetylcholinesterase and the facilitation of neuromuscular transmission has been studied in the rat after the administration of neostigmine, pyridostigmine, edrophonium and 3-hydroxyphenyltrimethyl-ammonium (3-OH PTMA). 2 After the administration of neostigmine or pyridostigmine, acetylcholinesterase activity recovered only slowly due to the covalent nature of the inhibition. In contrast, recovery from the reversible inhibition caused by edrophonium or 3-OH PTMA was rapid and showed a direct relationship to the plasma concentration of these drugs. 3 There was a statistically significant linear correlation between the logarithm of the plasma concentration of the drugs and the increase in the tibialis twitch tension. 4 The relationship between the inhibition of acetylcholinesterase and the facilitation of neuromuscular transmission was complex. When the enzyme was less than 85% inhibited no facilitation occurred. Between 85% and 98% inhibition, facilitation was linearly related to enzyme inhibition. Above 98% inhibition, facilitation was unrelated to inhibition of the enzyme."}
{"id": "PMID:223709", "title": "An assessment of computerised isotopic renal section scanning.", "content": "The basic non-invasive investigation of renal space occupying lesions by excretion pyelography was coupled with ultrasonic scanning. Forty-one patients who have undergone isotopic section scanning as part of their investigative assessment were studied. The conditions investigated included solitary cysts, polycystic kidneys, renal tumours, tumefactive xanthomatous pyelonephritis, renal infarct and non-functioning kidneys. An analysis of the accuracy of isotopic section scanning in these different pathological states was made. Computerised isotopic section renal scanning offers a new non-invasive renal investigative technique.", "contents": "An assessment of computerised isotopic renal section scanning. The basic non-invasive investigation of renal space occupying lesions by excretion pyelography was coupled with ultrasonic scanning. Forty-one patients who have undergone isotopic section scanning as part of their investigative assessment were studied. The conditions investigated included solitary cysts, polycystic kidneys, renal tumours, tumefactive xanthomatous pyelonephritis, renal infarct and non-functioning kidneys. An analysis of the accuracy of isotopic section scanning in these different pathological states was made. Computerised isotopic section renal scanning offers a new non-invasive renal investigative technique."}
{"id": "PMID:223711", "title": "Urinary inhibitor of the formation of calcium oxalate.", "content": "Normal urine was examined for substances which inhibited the formation of calcium oxalate, using a separation scheme which involved ultrafiltration, alcohol precipitation, electrophoresis and paper chromatography. The major anionic inhibitors were found to be citric acid, isocitric acid and pyrophosphate. The inhibitory activity of urine and that of an artificial urine having the same concentration of urea, creatinine, sodium, potassiu, magnesium, calcium, ammonia, sulphate, chloride, inorganic phosphate, oxalate, citrate, isocitrate and pyrophosphate, and the same pH were identical. This confirmed that urine does not contain an unidentified potent substance which inhibits the formation of calcium oxalate.", "contents": "Urinary inhibitor of the formation of calcium oxalate. Normal urine was examined for substances which inhibited the formation of calcium oxalate, using a separation scheme which involved ultrafiltration, alcohol precipitation, electrophoresis and paper chromatography. The major anionic inhibitors were found to be citric acid, isocitric acid and pyrophosphate. The inhibitory activity of urine and that of an artificial urine having the same concentration of urea, creatinine, sodium, potassiu, magnesium, calcium, ammonia, sulphate, chloride, inorganic phosphate, oxalate, citrate, isocitrate and pyrophosphate, and the same pH were identical. This confirmed that urine does not contain an unidentified potent substance which inhibits the formation of calcium oxalate."}
{"id": "PMID:223717", "title": "Growth and effect of chlamydiae in human and bovine oviduct organ cultures.", "content": "Organ cultures of 10 Fallopian tubes were inoculated with a genital strain of Chlamydia trachomatis and seven were infected. Infection was enhanced by centrifuging the organisms on to the tissues, larger numbers of organisms being reisolated from the tissues after this procedure. There was evidence of chlamydial multiplication because the number of organisms which were recovered from the tissues three to five days after inoculation had increased. Recovery was rare, however, after the sixth day, thus suggesting a self-limiting infection. Organ cultures of two bovine oviducts were infected with the bovine abortion strain of Chlamydia psittaci, but in these experiments centrifugation of the inocula did not enhance infection. The organisms were found in both the tissue and medium of cultures up to 18 days after inoculation and in much greater numbers than in the C. trachomatis-infected Fallopian cultures. Chlamydial infection was not entirely host-tissue specific, because C. trachomatis organisms were isolated from bovine oviduct cultures. Inclusions, however, were not detected histologically or electron microscopically in the epithelium of C. trachomatis-infected cultures, but they were detected by these means in C. psittaci-infected bovine cultures. All the elements of the chlamydial growth cycle were seen by electron microscopy, organisms being found in ciliated and possibly non-ciliated cells, and shedding of some infected epithelial cells was observed. No evidence of extensive epithelial cell damage was observed, however, and no loss of ciliary activity was detected in cultures infected with either C. trachomatis or C. psittaci when compared with uninoculated cultures. Thus acute salpingitis, when caused by chlamydial infection, is probably immunologically mediated.", "contents": "Growth and effect of chlamydiae in human and bovine oviduct organ cultures. Organ cultures of 10 Fallopian tubes were inoculated with a genital strain of Chlamydia trachomatis and seven were infected. Infection was enhanced by centrifuging the organisms on to the tissues, larger numbers of organisms being reisolated from the tissues after this procedure. There was evidence of chlamydial multiplication because the number of organisms which were recovered from the tissues three to five days after inoculation had increased. Recovery was rare, however, after the sixth day, thus suggesting a self-limiting infection. Organ cultures of two bovine oviducts were infected with the bovine abortion strain of Chlamydia psittaci, but in these experiments centrifugation of the inocula did not enhance infection. The organisms were found in both the tissue and medium of cultures up to 18 days after inoculation and in much greater numbers than in the C. trachomatis-infected Fallopian cultures. Chlamydial infection was not entirely host-tissue specific, because C. trachomatis organisms were isolated from bovine oviduct cultures. Inclusions, however, were not detected histologically or electron microscopically in the epithelium of C. trachomatis-infected cultures, but they were detected by these means in C. psittaci-infected bovine cultures. All the elements of the chlamydial growth cycle were seen by electron microscopy, organisms being found in ciliated and possibly non-ciliated cells, and shedding of some infected epithelial cells was observed. No evidence of extensive epithelial cell damage was observed, however, and no loss of ciliary activity was detected in cultures infected with either C. trachomatis or C. psittaci when compared with uninoculated cultures. Thus acute salpingitis, when caused by chlamydial infection, is probably immunologically mediated."}
{"id": "PMID:223718", "title": "Distribution of PNS myelin proteins and membrane enzymes in fractions isolated by continuous gradient zonal centrifugation.", "content": "Myelin was purified from adult rabbit sciatic nerve by two procedures: discontinuous gradient centrifugation and continuous gradient zonal centrifugation. Two fractions were obtained from the discontinuous gradient. The fraction floating on 0.32 M sucrose and the fraction recovered from the 0.32/0.85 M sucrose interface showed typical myelin membranes by electron microscopy and typical myelin proteins by gel electrophoresis. The specific activity of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) decreased from the top to the bottom of the discontinuous gradient. The myelin separated by zonal centrifugation on a continuous sucrose gradient showed three distinct peaks (on monitoring optical density) at 0.10, 0.30 and 0.57 M sucrose. The latter peak yielded 92% of the material applied. The two minor peaks of low density exhibited high CNP and acetylcholinesterase (AChE) activities but the specific activity of both enzymes increased markedly at the heavy end of the gradient. The zonal fractions showed typical myelin proteins in all fractions by polyacrylamide gel electrophoresis but with important quantitative differences. These results indicate that PNS myelin shows significant heterogeneity.", "contents": "Distribution of PNS myelin proteins and membrane enzymes in fractions isolated by continuous gradient zonal centrifugation. Myelin was purified from adult rabbit sciatic nerve by two procedures: discontinuous gradient centrifugation and continuous gradient zonal centrifugation. Two fractions were obtained from the discontinuous gradient. The fraction floating on 0.32 M sucrose and the fraction recovered from the 0.32/0.85 M sucrose interface showed typical myelin membranes by electron microscopy and typical myelin proteins by gel electrophoresis. The specific activity of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) decreased from the top to the bottom of the discontinuous gradient. The myelin separated by zonal centrifugation on a continuous sucrose gradient showed three distinct peaks (on monitoring optical density) at 0.10, 0.30 and 0.57 M sucrose. The latter peak yielded 92% of the material applied. The two minor peaks of low density exhibited high CNP and acetylcholinesterase (AChE) activities but the specific activity of both enzymes increased markedly at the heavy end of the gradient. The zonal fractions showed typical myelin proteins in all fractions by polyacrylamide gel electrophoresis but with important quantitative differences. These results indicate that PNS myelin shows significant heterogeneity."}
{"id": "PMID:223721", "title": "Evidence that an excitatory connection between the periaqueductal gray and nucleus raphe magnus mediates stimulation produced analgesia.", "content": "Both electrical stimulation and injection of morphine into the midbrain periaqueductal gray (PAG) produce analgesia in the rat. There is evidence that this analgesic effect is mediated by a descending system that involves nucleus raphe magnus (NRM) and adjacent reticular formation. In the studies reported here, the activity of the cells in the PAG was increased by microinjection of glutamate in this area and its effect on both the activity of single cells in the NRM and on a flexion reflex elicited by noxious heat was measured. It is shown that an increase in the firing rate of the cells in the PAG is associated with a raised threshold for flexion and is also correlated with an increase in the firing rate of a majority of the cells in the NRM. This effect on the flexion reflex can be abolished by (a) lesion of the nucleus raphe magnus and a small area of the reticular formation surrounding this nucleus and (b) by nalazone 20 min after its i.v. injection. It is concluded that there is an excitatory connection between the periaqueductal gray and the nucleus raphe magnus and that activation of this system can cause analgesia.", "contents": "Evidence that an excitatory connection between the periaqueductal gray and nucleus raphe magnus mediates stimulation produced analgesia. Both electrical stimulation and injection of morphine into the midbrain periaqueductal gray (PAG) produce analgesia in the rat. There is evidence that this analgesic effect is mediated by a descending system that involves nucleus raphe magnus (NRM) and adjacent reticular formation. In the studies reported here, the activity of the cells in the PAG was increased by microinjection of glutamate in this area and its effect on both the activity of single cells in the NRM and on a flexion reflex elicited by noxious heat was measured. It is shown that an increase in the firing rate of the cells in the PAG is associated with a raised threshold for flexion and is also correlated with an increase in the firing rate of a majority of the cells in the NRM. This effect on the flexion reflex can be abolished by (a) lesion of the nucleus raphe magnus and a small area of the reticular formation surrounding this nucleus and (b) by nalazone 20 min after its i.v. injection. It is concluded that there is an excitatory connection between the periaqueductal gray and the nucleus raphe magnus and that activation of this system can cause analgesia."}
{"id": "PMID:223722", "title": "Role of the nucleus raphe magnus in opiate analgesia as studied by the microinjection technique in the rat.", "content": "The analgesic effects of morphine (5 microgram, 0.2 microliter) microinjected into the nucleus raph\u00e9 magnus (NRM) and the surrounding reticular formation of the rat were tested using vocalization after electric shock to the tail as the test for analgesia. Only sites in the NRM produced powerful analgesic effects, strongest analgesia being equivalent to 3 mg/kg i.v. morphine. The analgesia produced by the microinjection was reversed by systemic naloxone. Pretreatment with systemic cinanserin, a blocker of serotonergic receptors, led to a pronounced diminution of the analgesic effects of the morphine. The effects of microinjections of naloxone (5 microgram 0.2 microliter) were studied for their effect on analgesia produced by systemic morphine. The analgesia following 3 mg/kg i.v. morphine was diminished by the microinjection of naloxone but the naloxone almost completely reversed the analgesic effects of 1.5 mg/kg i.v. morphine. These results further substantiate the role of the NRM in analgesic mechanisms.", "contents": "Role of the nucleus raphe magnus in opiate analgesia as studied by the microinjection technique in the rat. The analgesic effects of morphine (5 microgram, 0.2 microliter) microinjected into the nucleus raph\u00e9 magnus (NRM) and the surrounding reticular formation of the rat were tested using vocalization after electric shock to the tail as the test for analgesia. Only sites in the NRM produced powerful analgesic effects, strongest analgesia being equivalent to 3 mg/kg i.v. morphine. The analgesia produced by the microinjection was reversed by systemic naloxone. Pretreatment with systemic cinanserin, a blocker of serotonergic receptors, led to a pronounced diminution of the analgesic effects of the morphine. The effects of microinjections of naloxone (5 microgram 0.2 microliter) were studied for their effect on analgesia produced by systemic morphine. The analgesia following 3 mg/kg i.v. morphine was diminished by the microinjection of naloxone but the naloxone almost completely reversed the analgesic effects of 1.5 mg/kg i.v. morphine. These results further substantiate the role of the NRM in analgesic mechanisms."}
{"id": "PMID:223723", "title": "Endogenous phosphorylation in vitro: differential effects of brain state (anesthesia, post-mortem) on electrophoretically separated brain proteins.", "content": "In vitro phosphorylation of rat cerebral cortex synaptosomes was measured in animals that had been acutely treated with sodium pentobarbital. [32P]Labelled phosphoproteins were separated by SDS-slab gel electrophoresis, and the autoradiographs were analyzed by densitometry. We report here that Band F of our previous reports can be separated into two components, F1 and F2, using an improved gel system. This separation is particularly relevant in this report since these components appear to be differentially sensitive to the manipulations used. Specifically, we found that while F1 phosphorylation was markedly diminished by deep barbiturate anesthesia, F2 was relatively stable. While phosphorylation of F2 was also stable 24 h post-mortem, Band F1 phosphorylation was no longer detectable. Finally, while osmotic shock treatment of synaptosomes reduced phosphorylation of F2 somewhat, it eliminated the in vitro phosphorylation of Band F1. We found that under light barbiturate anesthesia, just at the time when the animals lost the righting reflex, the in vitro phosphorylation of Bands D (MR 78,000--80,000 daltons), F1 (MR 47,000--49,000) and F2 (MR 40,000--45,000) increased relative to unanesthetized controls. The in vitro labelling of Bands D and F1 was depressed in tissue prepared from animals that were deeply comatose. These effects of pentobarbital were more pronounced when animals were sacrificed by liquid nitrogen immersion, rather than by decapitation. Cyclic AMP-dependent phosphorylation of Band D exhibited remarkable stability 24 h post-morten (7 days in one case), even when brain tissue was left at room temperature (21--23 degrees C). Phosphorylation of Band F1, however, was not detectable in post-mortem tissue. The results of these studies indicate that phosphorylation of Band F1 is: (1) sensitive to pentobarbital, and (2) unstable post-mortem. Previous findings from our laboratory suggest that Band F1 is: (3) increased in phosphorylation in liquid nitrogen P2 preparations, and may be (4) cAMP-independent, (5) rapidly turning over its phosphate in vivo, and (6) altered by a training experience. Other evidence suggests that: (7) Band F1 phosphorylation may be Ca2+-dependent and that: (8) its phosphorylation is sensitive to osmotic lysis of synaptosomes. The results suggest an important and perhaps unique role for Band F1 in neuronal function.", "contents": "Endogenous phosphorylation in vitro: differential effects of brain state (anesthesia, post-mortem) on electrophoretically separated brain proteins. In vitro phosphorylation of rat cerebral cortex synaptosomes was measured in animals that had been acutely treated with sodium pentobarbital. [32P]Labelled phosphoproteins were separated by SDS-slab gel electrophoresis, and the autoradiographs were analyzed by densitometry. We report here that Band F of our previous reports can be separated into two components, F1 and F2, using an improved gel system. This separation is particularly relevant in this report since these components appear to be differentially sensitive to the manipulations used. Specifically, we found that while F1 phosphorylation was markedly diminished by deep barbiturate anesthesia, F2 was relatively stable. While phosphorylation of F2 was also stable 24 h post-mortem, Band F1 phosphorylation was no longer detectable. Finally, while osmotic shock treatment of synaptosomes reduced phosphorylation of F2 somewhat, it eliminated the in vitro phosphorylation of Band F1. We found that under light barbiturate anesthesia, just at the time when the animals lost the righting reflex, the in vitro phosphorylation of Bands D (MR 78,000--80,000 daltons), F1 (MR 47,000--49,000) and F2 (MR 40,000--45,000) increased relative to unanesthetized controls. The in vitro labelling of Bands D and F1 was depressed in tissue prepared from animals that were deeply comatose. These effects of pentobarbital were more pronounced when animals were sacrificed by liquid nitrogen immersion, rather than by decapitation. Cyclic AMP-dependent phosphorylation of Band D exhibited remarkable stability 24 h post-morten (7 days in one case), even when brain tissue was left at room temperature (21--23 degrees C). Phosphorylation of Band F1, however, was not detectable in post-mortem tissue. The results of these studies indicate that phosphorylation of Band F1 is: (1) sensitive to pentobarbital, and (2) unstable post-mortem. Previous findings from our laboratory suggest that Band F1 is: (3) increased in phosphorylation in liquid nitrogen P2 preparations, and may be (4) cAMP-independent, (5) rapidly turning over its phosphate in vivo, and (6) altered by a training experience. Other evidence suggests that: (7) Band F1 phosphorylation may be Ca2+-dependent and that: (8) its phosphorylation is sensitive to osmotic lysis of synaptosomes. The results suggest an important and perhaps unique role for Band F1 in neuronal function."}
{"id": "PMID:223724", "title": "Effects of opiate-like peptides, morphine, and naloxone in the photosensitive baboon, Papio papio.", "content": "The effects of intracerebroventricular (i.c.v.) or systemic injections of Met- or Leu-enkephalin, beta-endorphin, FK 33.824 (D-Ala2, MePhe4, Met(O5)-ol-enkephalin) and of morphine and naloxone have been studied in baboons, Papio papio, which spontaneously show photically induced epileptic responses. Animals were chronically implanted with epidural or deep recording electrodes and a cannula in one lateral ventricle, and tested whilst seated in a primate chair. In some animals the natural syndrome was enhanced by the prior administration of DL-allylglycine, 100--200 mg/kg, i.v. Met- or Leu-enkephalin, 1--10 mg, i.c.v., did not lead to any manifest focal or generalized seizure discharges. Nor did it lead to any consistent enhancement or reduction of photically induced myoclonic responses (as tested 5--10 min after injection). beta-Endorphin, 0.1--0.5 mg, i.c.v., did not enhance or impair photically induced myoclonic responses. FK 33.824, 0.1--0.5 mg, i.c.v., depressed respiration and slowed EEG background rhythms for 9--15 h. This was associated with a loss of myoclonic responses to photic stimulation. These effects were reversed for 20--40 min following the injection of naloxone, 1 mg/kg i.m. A depression of respiration and a slowing of EEG rhythms was seen beginning 5--20 min after FK 33.824, 2 or 4 mg/kg, i.v. The higher dose also abolished photically induced myoclonic responses. Naloxone, 1 mg/kg, definitively reversed these effects. Morphine, 5--10 mg i.c.v., tended to increase the latency to onset of generalized myoclonus during photic stimulation. Myoclonic responses were delayed or diminished after morphine, 5 mg/kg, i.m. Naloxone, 1--2 mg/kg i.m., reversed this effect. Naloxone, 0.2--5.0 mg/kg i.m., alone, did not significantly modify photically induced myoclonus, either in animals of low or high initial responsiveness, or in those pretreated with allylglycine.", "contents": "Effects of opiate-like peptides, morphine, and naloxone in the photosensitive baboon, Papio papio. The effects of intracerebroventricular (i.c.v.) or systemic injections of Met- or Leu-enkephalin, beta-endorphin, FK 33.824 (D-Ala2, MePhe4, Met(O5)-ol-enkephalin) and of morphine and naloxone have been studied in baboons, Papio papio, which spontaneously show photically induced epileptic responses. Animals were chronically implanted with epidural or deep recording electrodes and a cannula in one lateral ventricle, and tested whilst seated in a primate chair. In some animals the natural syndrome was enhanced by the prior administration of DL-allylglycine, 100--200 mg/kg, i.v. Met- or Leu-enkephalin, 1--10 mg, i.c.v., did not lead to any manifest focal or generalized seizure discharges. Nor did it lead to any consistent enhancement or reduction of photically induced myoclonic responses (as tested 5--10 min after injection). beta-Endorphin, 0.1--0.5 mg, i.c.v., did not enhance or impair photically induced myoclonic responses. FK 33.824, 0.1--0.5 mg, i.c.v., depressed respiration and slowed EEG background rhythms for 9--15 h. This was associated with a loss of myoclonic responses to photic stimulation. These effects were reversed for 20--40 min following the injection of naloxone, 1 mg/kg i.m. A depression of respiration and a slowing of EEG rhythms was seen beginning 5--20 min after FK 33.824, 2 or 4 mg/kg, i.v. The higher dose also abolished photically induced myoclonic responses. Naloxone, 1 mg/kg, definitively reversed these effects. Morphine, 5--10 mg i.c.v., tended to increase the latency to onset of generalized myoclonus during photic stimulation. Myoclonic responses were delayed or diminished after morphine, 5 mg/kg, i.m. Naloxone, 1--2 mg/kg i.m., reversed this effect. Naloxone, 0.2--5.0 mg/kg i.m., alone, did not significantly modify photically induced myoclonus, either in animals of low or high initial responsiveness, or in those pretreated with allylglycine."}
{"id": "PMID:223726", "title": "Blockade of progesterone-induced increase in hypothalamic luteinizing hormone-releasing hormone levels and serum gonadotropins by intrahypothalamic implantation of 6-hydroxydopamine.", "content": "The present study was undertaken to identify the hypothalamic locus where norepinephrine (NE) nerve terminals communicate with luteinizing hormone-releasing hormone (LH-RH)-containing neurons involved in the stimulatory feedback action of gonadal steroids on LH and FSH release. Ovariectomized rats received estradiol benzoate (10 microgram/rat s.c.) on day 0. Intracranial implants containing either 6-hydroxydopamine (6-OHDA), to destroy NE terminals, or cocoa butter (controls) were placed bilaterally in the suprachiasmatic nucleus (SCN), medial basal hypothalamus (MBH) or olfactory tubercle (OT) on day 1. Progesterone (P, 5 mg/rat s.c.) was administered at 10.00 h on day 2 to elicit increases in serum LH and FSH and the MBH LH-RH levels in the afternoon. Implantation of 6-OHDA in the SCN resulted in a marked depletion of NE in and around the region of the SCN in the preoptic-anterior hypothalamic area (POA-AH) without adversely affecting dopamine (DA) concentrations, and blocked the P-induced afternoon increase in the MBH LH-RH and serum gonadotropin levels. Similar reduction in the MBH NE concentrations occurred following placement of 6-OHDA in the MBH; however, these as well as implants in the OT were ineffective in suppressing the P-induced effects. These studies show that functional integrity of the SCN regions is critical in manifestation of the P-induced rise in the MBH LH-RH activity, and this region in the POA-AH, therefore, may be the primary locus of synaptic communication between NE terminals and LH-RH neurons.", "contents": "Blockade of progesterone-induced increase in hypothalamic luteinizing hormone-releasing hormone levels and serum gonadotropins by intrahypothalamic implantation of 6-hydroxydopamine. The present study was undertaken to identify the hypothalamic locus where norepinephrine (NE) nerve terminals communicate with luteinizing hormone-releasing hormone (LH-RH)-containing neurons involved in the stimulatory feedback action of gonadal steroids on LH and FSH release. Ovariectomized rats received estradiol benzoate (10 microgram/rat s.c.) on day 0. Intracranial implants containing either 6-hydroxydopamine (6-OHDA), to destroy NE terminals, or cocoa butter (controls) were placed bilaterally in the suprachiasmatic nucleus (SCN), medial basal hypothalamus (MBH) or olfactory tubercle (OT) on day 1. Progesterone (P, 5 mg/rat s.c.) was administered at 10.00 h on day 2 to elicit increases in serum LH and FSH and the MBH LH-RH levels in the afternoon. Implantation of 6-OHDA in the SCN resulted in a marked depletion of NE in and around the region of the SCN in the preoptic-anterior hypothalamic area (POA-AH) without adversely affecting dopamine (DA) concentrations, and blocked the P-induced afternoon increase in the MBH LH-RH and serum gonadotropin levels. Similar reduction in the MBH NE concentrations occurred following placement of 6-OHDA in the MBH; however, these as well as implants in the OT were ineffective in suppressing the P-induced effects. These studies show that functional integrity of the SCN regions is critical in manifestation of the P-induced rise in the MBH LH-RH activity, and this region in the POA-AH, therefore, may be the primary locus of synaptic communication between NE terminals and LH-RH neurons."}
{"id": "PMID:223730", "title": "Changes in the visual system of monocularly sutured or enucleated cats demonstrable with cytochrome oxidase histochemistry.", "content": "Endogenous cytochrome oxidase activity within the mitochondria of neurons and neuropil was demonstrated histochemically under normal and experimental conditions. Since enzymatic changes were noted with chronic neuronal inactivity in the auditory system (Wong-Riley et al), the present study sought to examine functionally induced enzymatic changes in the visual system of kittens. Eight kittens were used experimentally: 5 had monocular lid suture for varying periods of time; one had binocular lid suture followed by monocular suture followed by binocular opening; two had monocular enucleation. All initial procedures were performed before eye opening. Materials from other normal kittens and cats were also used as controls. At the end of the experiments, the animals were perfused with aldehyde solutions and frozen sections of the brains were incubated for cytochrome oxidase activity (a detailed protocol was outlined). The results indicated that the deprivation caused by monocular suture produced a decrease in the cytochrome oxidase staining of the binocular segment of the deprived geniculate laminae. Enucleation yielded a greater decrease in the cytochrome oxidase activity in the affected geniculate laminae. However, the staining in the 'normal' lamina extended across the interlaminar border to include a row of surviving large cells in the 'denervated' lamina. The staining of the monocular segment appeared not to be affected by lid suture, but was decreased by enucleation. At the cortical level, lamina IV in area 17 of normal cats was stained darkly as a continuous band. Following lid suture, this pattern was replaced in part by alternating columns of light and dark staining, suggestive of ocular dominance columns. Thus, a decrease in neuronal activity due to reduced visual stimulation or destruction of the primary afferent nerves led to a significant decrease in the level of oxidative enzyme activity one to several synapses away.", "contents": "Changes in the visual system of monocularly sutured or enucleated cats demonstrable with cytochrome oxidase histochemistry. Endogenous cytochrome oxidase activity within the mitochondria of neurons and neuropil was demonstrated histochemically under normal and experimental conditions. Since enzymatic changes were noted with chronic neuronal inactivity in the auditory system (Wong-Riley et al), the present study sought to examine functionally induced enzymatic changes in the visual system of kittens. Eight kittens were used experimentally: 5 had monocular lid suture for varying periods of time; one had binocular lid suture followed by monocular suture followed by binocular opening; two had monocular enucleation. All initial procedures were performed before eye opening. Materials from other normal kittens and cats were also used as controls. At the end of the experiments, the animals were perfused with aldehyde solutions and frozen sections of the brains were incubated for cytochrome oxidase activity (a detailed protocol was outlined). The results indicated that the deprivation caused by monocular suture produced a decrease in the cytochrome oxidase staining of the binocular segment of the deprived geniculate laminae. Enucleation yielded a greater decrease in the cytochrome oxidase activity in the affected geniculate laminae. However, the staining in the 'normal' lamina extended across the interlaminar border to include a row of surviving large cells in the 'denervated' lamina. The staining of the monocular segment appeared not to be affected by lid suture, but was decreased by enucleation. At the cortical level, lamina IV in area 17 of normal cats was stained darkly as a continuous band. Following lid suture, this pattern was replaced in part by alternating columns of light and dark staining, suggestive of ocular dominance columns. Thus, a decrease in neuronal activity due to reduced visual stimulation or destruction of the primary afferent nerves led to a significant decrease in the level of oxidative enzyme activity one to several synapses away."}
{"id": "PMID:223731", "title": "Potentiation of the effects of GABA by pentobarbitone.", "content": "Pentobarbitone (50 microM) has been shown to potentiate GABA-induced responses in rat isolated superior cervical ganglia and in dorsal or ventral root fibres of immature rat isolated spinal cords. Measurements of dose ratios for the antagonism of GABA-induced responses of dorsal root fibres by bicuculline showed that pentobarbitone (50 microM) did not significantly alter this antagonism. This result indicates that the antagonism of GABA by bucuculline at dorsal root fibres is not reversed by pentobarbitone. Ventral root responses to GABA (but not glycine) were also potentiated by pentobarbitone (+/-)-Nipecotic acid (300 microM) potentiated responses to GABA much more than those to 3-aminopropane-sulphonic acid.", "contents": "Potentiation of the effects of GABA by pentobarbitone. Pentobarbitone (50 microM) has been shown to potentiate GABA-induced responses in rat isolated superior cervical ganglia and in dorsal or ventral root fibres of immature rat isolated spinal cords. Measurements of dose ratios for the antagonism of GABA-induced responses of dorsal root fibres by bicuculline showed that pentobarbitone (50 microM) did not significantly alter this antagonism. This result indicates that the antagonism of GABA by bucuculline at dorsal root fibres is not reversed by pentobarbitone. Ventral root responses to GABA (but not glycine) were also potentiated by pentobarbitone (+/-)-Nipecotic acid (300 microM) potentiated responses to GABA much more than those to 3-aminopropane-sulphonic acid."}
{"id": "PMID:223734", "title": "Turnover of phosphatidyl choline and changes in enzymatic activity in cell membranes of the CNS during early myelination.", "content": "Subfractions of fraction A, which floats on top on 0.8 M sucrose in the classical density gradient used for the isolation of brain subcellular fractions (A1 corresponding in adult rats to myelin and A2 which corresponds to the myelin-like fraction), were studied in comparison to other brain subcellular fractions in 5 day old rats and at different stages of development, up to 60 days of age. Variations in the enzymatic activity of acetylcholinesterase, non-specific cholinesterase and 2',3'-Cyclic nucleotide phosphohydrolase, changes in lipid and protein composition and turnover of phosphatidyl choline were investigated. Results indicate that fractions A1 and A2 obtained prior to the beginning of myelination could be composed of fragments of the oligodendroglial cell plasma membranes, and that both fractions undergo substantial changes in chemical composition, enzymatic activity and in turnover of phosphatidyl choline during maturation. In vivo experiments at short times, using radioactive choline as a precursor of phosphatidylcholine suggest that membrane fragments isolated in fraction A2 are precursors of those isolated in fraction A1 at all ages.", "contents": "Turnover of phosphatidyl choline and changes in enzymatic activity in cell membranes of the CNS during early myelination. Subfractions of fraction A, which floats on top on 0.8 M sucrose in the classical density gradient used for the isolation of brain subcellular fractions (A1 corresponding in adult rats to myelin and A2 which corresponds to the myelin-like fraction), were studied in comparison to other brain subcellular fractions in 5 day old rats and at different stages of development, up to 60 days of age. Variations in the enzymatic activity of acetylcholinesterase, non-specific cholinesterase and 2',3'-Cyclic nucleotide phosphohydrolase, changes in lipid and protein composition and turnover of phosphatidyl choline were investigated. Results indicate that fractions A1 and A2 obtained prior to the beginning of myelination could be composed of fragments of the oligodendroglial cell plasma membranes, and that both fractions undergo substantial changes in chemical composition, enzymatic activity and in turnover of phosphatidyl choline during maturation. In vivo experiments at short times, using radioactive choline as a precursor of phosphatidylcholine suggest that membrane fragments isolated in fraction A2 are precursors of those isolated in fraction A1 at all ages."}
{"id": "PMID:223737", "title": "The bulbo-spinal indoleaminergic pathway in the frog.", "content": "The role of the bulbo-spinal indoleaminergic pathway of the frog was investigated. Using the isolated spinal cord preparation, responses of motoneurons of segments 9 and 10 to lateral column stimulation were recorded from ventral roots (LC-VRP) and by intracellularly placed microelectrodes. Control responses were compared to those obtained after addition of substances known to alter indoleaminergic synthesis or receptor activation. Responses from spinal cords of animals that were pretreated with indoleamine-depleting agents were compared to mean control responses. Procedures that inhibited indoleamine synthesis or blocked indoleamine receptors reduced motoneuronal activity. This was manifested as an increase in mean latency and a decrease in amplitude of the monosynaptic LC-VRP, an increased duration of suppression following an LC conditioning stimulus, and a decrease in spontaneous activity. In contrast to intracellularly recorded responses from control cords, those recorded under these conditions typically showed single spikes with longer latencies. Additions of indoleamine precursors to normal cords or to cords depleted of monoamines by reserpine shortened mean latencies, increased amplitudes of LC-elicited responses and caused an increase in spontaneous activity. These observations were recorded both extracellularly and intracellularly. Our results suggest that the bulbo-spinal indoleaminergic pathway modulates the output of motoneurons of the frog spinal cord.", "contents": "The bulbo-spinal indoleaminergic pathway in the frog. The role of the bulbo-spinal indoleaminergic pathway of the frog was investigated. Using the isolated spinal cord preparation, responses of motoneurons of segments 9 and 10 to lateral column stimulation were recorded from ventral roots (LC-VRP) and by intracellularly placed microelectrodes. Control responses were compared to those obtained after addition of substances known to alter indoleaminergic synthesis or receptor activation. Responses from spinal cords of animals that were pretreated with indoleamine-depleting agents were compared to mean control responses. Procedures that inhibited indoleamine synthesis or blocked indoleamine receptors reduced motoneuronal activity. This was manifested as an increase in mean latency and a decrease in amplitude of the monosynaptic LC-VRP, an increased duration of suppression following an LC conditioning stimulus, and a decrease in spontaneous activity. In contrast to intracellularly recorded responses from control cords, those recorded under these conditions typically showed single spikes with longer latencies. Additions of indoleamine precursors to normal cords or to cords depleted of monoamines by reserpine shortened mean latencies, increased amplitudes of LC-elicited responses and caused an increase in spontaneous activity. These observations were recorded both extracellularly and intracellularly. Our results suggest that the bulbo-spinal indoleaminergic pathway modulates the output of motoneurons of the frog spinal cord."}
{"id": "PMID:223738", "title": "Isotherm of alcohol-cooled cryoprobe.", "content": "The spread of cooling from the tip of a cryoprobe placed in the ventral posterior lateral nucleus of the thalamus in 10 cats was determined. A 20 degrees C isotherm was described as having a diameter of 4 mm and extending 2 mm below the tip of the cryoprobe and tapering up along the shaft of the cryoprobe for a distance of 2 mm, when the cryoprobe tip temperature was maintained at 3 degrees C.", "contents": "Isotherm of alcohol-cooled cryoprobe. The spread of cooling from the tip of a cryoprobe placed in the ventral posterior lateral nucleus of the thalamus in 10 cats was determined. A 20 degrees C isotherm was described as having a diameter of 4 mm and extending 2 mm below the tip of the cryoprobe and tapering up along the shaft of the cryoprobe for a distance of 2 mm, when the cryoprobe tip temperature was maintained at 3 degrees C."}
{"id": "PMID:223743", "title": "Feedback loop between locus coeruleus and spinal trigeminal nucleus neurons responding to tooth pulp stimulation in the rat.", "content": "Studies were performed to elucidate reciprocal relationships between locus coeruleus (LC) and spinal trigeminal nucleus (STN) neurons responding to tooth pulp (TP) stimulation using rats anesthetized with alpha-chloralose. LC conditioning stimulation inhibited STN field potential as well as orthodromic spike generation of STN neurons produced by ipsilateral TP stimulation, confirming the previous findings in cats that LC neurons played an inhibitory role in the orthodromic transmission in STN neurons. Forty-one out of 56 LC neurons were activated by ipsilateral TP stimulation and 12 neurons by stimulation of both ipsi- and contralateral TP. STN stimulation usually excited LC neurons with a significantly shorter latency than did TP stimulation, including three LC neurons with a latency of less than 2.0 msec. These results indicate the existence of input from TP to LC neurons via multisynapses. In addition, neurons antidromically activated by STN stimulation were found in LC. It is highly probable, therefore, that there is a feedback loop between LC and STN, which might control input from TP to STN.", "contents": "Feedback loop between locus coeruleus and spinal trigeminal nucleus neurons responding to tooth pulp stimulation in the rat. Studies were performed to elucidate reciprocal relationships between locus coeruleus (LC) and spinal trigeminal nucleus (STN) neurons responding to tooth pulp (TP) stimulation using rats anesthetized with alpha-chloralose. LC conditioning stimulation inhibited STN field potential as well as orthodromic spike generation of STN neurons produced by ipsilateral TP stimulation, confirming the previous findings in cats that LC neurons played an inhibitory role in the orthodromic transmission in STN neurons. Forty-one out of 56 LC neurons were activated by ipsilateral TP stimulation and 12 neurons by stimulation of both ipsi- and contralateral TP. STN stimulation usually excited LC neurons with a significantly shorter latency than did TP stimulation, including three LC neurons with a latency of less than 2.0 msec. These results indicate the existence of input from TP to LC neurons via multisynapses. In addition, neurons antidromically activated by STN stimulation were found in LC. It is highly probable, therefore, that there is a feedback loop between LC and STN, which might control input from TP to STN."}
{"id": "PMID:223747", "title": "[Effect of stimulation of alpha and beta presynaptic adrenoceptors on the liberation of noradrenaline produced by electric stimulation in rabbit carotid sinus].", "content": "The experiments carried out on the isolated carotid sinus in the rabbit demonstrated that alpha and beta adrenoceptors are capable of detecting the circulating catecholamines and the catecholamines of the synaptic cleft in order to modulate the release of noradrenaline from the sympathetic nerve endings in response to a potential action.", "contents": "[Effect of stimulation of alpha and beta presynaptic adrenoceptors on the liberation of noradrenaline produced by electric stimulation in rabbit carotid sinus]. The experiments carried out on the isolated carotid sinus in the rabbit demonstrated that alpha and beta adrenoceptors are capable of detecting the circulating catecholamines and the catecholamines of the synaptic cleft in order to modulate the release of noradrenaline from the sympathetic nerve endings in response to a potential action."}
{"id": "PMID:223748", "title": "[Cellular receptors of gonadotropic hormones. Immunocytochemical evidence in rat testicle].", "content": "We have performed topical applications of HCG and LH on fixed paraffin-embedded sections of adult rat testes. Thereafter, immuno-cytochemical demonstration of the peptides was carried on and demonstrated that HCG and LH specifically bound to the cell membrane of Leydig cells. This technique is highly reproductible provided that adequate fixation (with formalin containing fixatives) as been performed.", "contents": "[Cellular receptors of gonadotropic hormones. Immunocytochemical evidence in rat testicle]. We have performed topical applications of HCG and LH on fixed paraffin-embedded sections of adult rat testes. Thereafter, immuno-cytochemical demonstration of the peptides was carried on and demonstrated that HCG and LH specifically bound to the cell membrane of Leydig cells. This technique is highly reproductible provided that adequate fixation (with formalin containing fixatives) as been performed."}
{"id": "PMID:223749", "title": "[Fate of Leydig cells in testicular organ culture].", "content": "In organ culture experiments, the Leydig cells of mouse testes can still be recognized after 12 days at 31 degrees C. HCG binding sites are effectively demonstrated. Meanwhile, when HCG is added at the initiation of the cultures, it is selectively stored in the cytoplasm of the Leydig cells. These findings point to a fairly good survival of Leydig cells in our tissue culture system.", "contents": "[Fate of Leydig cells in testicular organ culture]. In organ culture experiments, the Leydig cells of mouse testes can still be recognized after 12 days at 31 degrees C. HCG binding sites are effectively demonstrated. Meanwhile, when HCG is added at the initiation of the cultures, it is selectively stored in the cytoplasm of the Leydig cells. These findings point to a fairly good survival of Leydig cells in our tissue culture system."}
{"id": "PMID:223744", "title": "Differences in norepinephrine and dopamine neurotransmitter storage systems.", "content": "Low doses of d-amphetamine (d-AMP) produced a 50% or greater decrease in the firing rates of both dopamine (DA) neurons (substantia nigra zone compacta) and norepinephrine (NE) neurons (locus coeruleus). However, pretreatment with the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (alpha-MT) blocked the d-AMP-induced reduction in DA neuron firing rate, but had no effect on the d-AMP-induced reduction in NE cell firing rate. Similarly, alpha-MT administered subsequent to d-AMP readily reversed the d-AMP-induced decrease in the firing rates of DA cells, but caused no significant reversal in NE cell firing rates. These electrophysiological findings, in conjunction with biochemical and behavioral data, support the hypothesis that there is a difference in the DA and NE neurotransmitter storage mechanism. In the DA neuron, there appears to be a slow transfer between stored and readily-releasable (newly synthesized) amine pools so that, following synthesis inhibition, there is little DA available for release. However, in the NE neuron, there is a more rapid mobilization of stored amine to readily releasable sites, such that d-AMP continues to cause the release of NE even though synthesis of transmitter is blocked.", "contents": "Differences in norepinephrine and dopamine neurotransmitter storage systems. Low doses of d-amphetamine (d-AMP) produced a 50% or greater decrease in the firing rates of both dopamine (DA) neurons (substantia nigra zone compacta) and norepinephrine (NE) neurons (locus coeruleus). However, pretreatment with the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (alpha-MT) blocked the d-AMP-induced reduction in DA neuron firing rate, but had no effect on the d-AMP-induced reduction in NE cell firing rate. Similarly, alpha-MT administered subsequent to d-AMP readily reversed the d-AMP-induced decrease in the firing rates of DA cells, but caused no significant reversal in NE cell firing rates. These electrophysiological findings, in conjunction with biochemical and behavioral data, support the hypothesis that there is a difference in the DA and NE neurotransmitter storage mechanism. In the DA neuron, there appears to be a slow transfer between stored and readily-releasable (newly synthesized) amine pools so that, following synthesis inhibition, there is little DA available for release. However, in the NE neuron, there is a more rapid mobilization of stored amine to readily releasable sites, such that d-AMP continues to cause the release of NE even though synthesis of transmitter is blocked."}
{"id": "PMID:223745", "title": "Monosynaptic facilitatory pathway from the hypothalamic ventromedial nucleus to the frontal cortex in the rat.", "content": "Stimulation of the ventromedial nucleus (VMH) evoked a short latency negative wave with two peaks (cN1 and cN2) followed by a small positive wave (cP) at the ipsilateral dorsal frontal cortex (area 10) in the rat. The maximum response was observed from the lateral edge of the frontal pole. From the depth profiles of recordings, cN1 changed polarity at a depth of about 4 mm and the cN1-cN2 changed into a large compound action potential at the medioventral part of the frontal pole at a depth of about 6 mm. Since the surface evoked potential and the compound action potential followed high frequency stimulation, these respective potentials are concluded to be due to antidromic and monosynaptic activation of the cortical neurons. This was verified by unit recording experiments. The cP was concluded to be produced by the initial rise of the monosynaptic EPSP.", "contents": "Monosynaptic facilitatory pathway from the hypothalamic ventromedial nucleus to the frontal cortex in the rat. Stimulation of the ventromedial nucleus (VMH) evoked a short latency negative wave with two peaks (cN1 and cN2) followed by a small positive wave (cP) at the ipsilateral dorsal frontal cortex (area 10) in the rat. The maximum response was observed from the lateral edge of the frontal pole. From the depth profiles of recordings, cN1 changed polarity at a depth of about 4 mm and the cN1-cN2 changed into a large compound action potential at the medioventral part of the frontal pole at a depth of about 6 mm. Since the surface evoked potential and the compound action potential followed high frequency stimulation, these respective potentials are concluded to be due to antidromic and monosynaptic activation of the cortical neurons. This was verified by unit recording experiments. The cP was concluded to be produced by the initial rise of the monosynaptic EPSP."}
{"id": "PMID:223750", "title": "Anticonvulsant drug-induced osteomalacia: alterations in mineral metabolism and response to vitamin D3 administration.", "content": "Parameters of mineral metabolism were examined in 6 patients with moderately severe anticonvulsant drug-induced osteomalacia. Compared to 15 matched controls, the patients exhibited significantly reduced serum calcium, inorganic phosphate, and 25-hydroxyvitamin D concentration, elevated serum alkaline phosphatase and immunoreactive parathyroid hormone (iPTH) concentration, reduced intestinal 47Ca absorption, reduced urinary calcium and increased urinary hydroxyproline excretion, and reduced forearm bone mass. Intestinal absorption of vitamin D3 was normal. Following 4 months of treatment with vitamin D3 (4000 units/day), serum 25-OHD concentration was increased to 3 times mean normal values and all parameters except serum iPTH, urinary calcium excretion, and forearm bone mass were returned to levels not significantly different from normal. Serum iPTH concentration was reduced by 39% (P less than 0.05); 24-h urinary calcium excretion rose by 98% (P less than 0.001), and forearm bone mass increased by 5.6% (P less than 0.05). It is concluded that moderate-dose vitamin D3 supplementation is effective in normalizing parameters of mineral metabolism in this disorder, despite evidence of resistance to the biologic effects of vitamin D.", "contents": "Anticonvulsant drug-induced osteomalacia: alterations in mineral metabolism and response to vitamin D3 administration. Parameters of mineral metabolism were examined in 6 patients with moderately severe anticonvulsant drug-induced osteomalacia. Compared to 15 matched controls, the patients exhibited significantly reduced serum calcium, inorganic phosphate, and 25-hydroxyvitamin D concentration, elevated serum alkaline phosphatase and immunoreactive parathyroid hormone (iPTH) concentration, reduced intestinal 47Ca absorption, reduced urinary calcium and increased urinary hydroxyproline excretion, and reduced forearm bone mass. Intestinal absorption of vitamin D3 was normal. Following 4 months of treatment with vitamin D3 (4000 units/day), serum 25-OHD concentration was increased to 3 times mean normal values and all parameters except serum iPTH, urinary calcium excretion, and forearm bone mass were returned to levels not significantly different from normal. Serum iPTH concentration was reduced by 39% (P less than 0.05); 24-h urinary calcium excretion rose by 98% (P less than 0.001), and forearm bone mass increased by 5.6% (P less than 0.05). It is concluded that moderate-dose vitamin D3 supplementation is effective in normalizing parameters of mineral metabolism in this disorder, despite evidence of resistance to the biologic effects of vitamin D."}
{"id": "PMID:223753", "title": "The effect of morphine on human neuromuscular transmission.", "content": "By utilizing high frequency nerve stimulation, we observed the effects of morphine sulphate, 0.5 mg.kg-1 on human neuromuscular transmission. Tetanic fade at 50, 100 and 200 hz did not change during the one hour period after infusion of morphine. Post-tetanic depression (PTD) of single twitch response increased progressively with time over the one-hour study period. This was most marked with the 100 and 200 hz tetanic frequencies. In contrast, control subjects displayed either no change, or a slight increase (post-tetanic facilitation; PTF), over a similar one-hour test period. We believe these results are best explained by a presynaptic action of morphine, whereby intraterminal mobilization of acetylcholine is impaired by the opiate narcotic drug.", "contents": "The effect of morphine on human neuromuscular transmission. By utilizing high frequency nerve stimulation, we observed the effects of morphine sulphate, 0.5 mg.kg-1 on human neuromuscular transmission. Tetanic fade at 50, 100 and 200 hz did not change during the one hour period after infusion of morphine. Post-tetanic depression (PTD) of single twitch response increased progressively with time over the one-hour study period. This was most marked with the 100 and 200 hz tetanic frequencies. In contrast, control subjects displayed either no change, or a slight increase (post-tetanic facilitation; PTF), over a similar one-hour test period. We believe these results are best explained by a presynaptic action of morphine, whereby intraterminal mobilization of acetylcholine is impaired by the opiate narcotic drug."}
{"id": "PMID:223755", "title": "Effects of lanthanum on the heart sarcolemmal ATPase and calcium binding activities.", "content": "Effects of lanthanum on Ca2+-ATPase, Mg2+-ATPase, Na+-K+-ATPase, and calcium binding activities were studied in rat heart sarcolemma. Ten to 100 micrometers lanthanum depressed significantly the Ca2+-ATPase activity and 50--200 micrometers lanthanum inhibited the calcium binding activity. Lineweaver-Burk plots of the Ca2+-ATPase activity showed that the inhibition by lanthanum was competitive with calcium concentration. Neither Mg2+-ATPase nor Na+-K+-ATPase activities were affected by lanthanum when the assay medium contained 1 mM EDTA; however, in the absence of EDTA, these enzyme activities were significantly decreased by 10--100 micrometers lanthanum. Rat hearts perfused with HEPES buffer containing 0.5 mM lanthanum showed electron-dense deposits restricted to the outer cell surface and the sarcolemma obtained from these hearts also had the deposits, indicating that the membrane fraction isolated by the hypotonic shock--LiBr treatment method is of sarcolemmal origin. The Ca2+-ATPase activity of the sarcolemma isolated from lanthanum-perfused hearts, unlike the Mg2+-ATPase, Na+-K+-ATPase, and calcium binding activities, was significantly less than the control value. From these observations it is suggested that lanthanum may influence calcium movement across the sarcolemma by affecting sarcolemmal ATPase and calcium binding activities.", "contents": "Effects of lanthanum on the heart sarcolemmal ATPase and calcium binding activities. Effects of lanthanum on Ca2+-ATPase, Mg2+-ATPase, Na+-K+-ATPase, and calcium binding activities were studied in rat heart sarcolemma. Ten to 100 micrometers lanthanum depressed significantly the Ca2+-ATPase activity and 50--200 micrometers lanthanum inhibited the calcium binding activity. Lineweaver-Burk plots of the Ca2+-ATPase activity showed that the inhibition by lanthanum was competitive with calcium concentration. Neither Mg2+-ATPase nor Na+-K+-ATPase activities were affected by lanthanum when the assay medium contained 1 mM EDTA; however, in the absence of EDTA, these enzyme activities were significantly decreased by 10--100 micrometers lanthanum. Rat hearts perfused with HEPES buffer containing 0.5 mM lanthanum showed electron-dense deposits restricted to the outer cell surface and the sarcolemma obtained from these hearts also had the deposits, indicating that the membrane fraction isolated by the hypotonic shock--LiBr treatment method is of sarcolemmal origin. The Ca2+-ATPase activity of the sarcolemma isolated from lanthanum-perfused hearts, unlike the Mg2+-ATPase, Na+-K+-ATPase, and calcium binding activities, was significantly less than the control value. From these observations it is suggested that lanthanum may influence calcium movement across the sarcolemma by affecting sarcolemmal ATPase and calcium binding activities."}
{"id": "PMID:223756", "title": "Effect of captopril (SQ 14225) on blood pressure, plasma renin activity and angiotensin I converting enzyme activity.", "content": "Seven patients with essential hypertension and seven patients with hypertension associated with renal artery stenosis received captopril (SQ 14225), an inhibitor of angiotensin I converting enzyme. There was a significant reduction in mean blood pressure, from 176/113 +/- 4/3 mm Hg during the control period to 140/90 +/- 5/3 mm Hg during captopril administration. Five patients received captopril alone and nine patients needed hydrochlorothiazide in addition to control their blood pressure. Captopril produced a significant increase in peripheral plasma renin activity. When measured 12 hours after the administration of captopril the angiotensin I converting enzyme activity was found to be similar to that during the control period even though the blood pressure was at or near normal. These findings indicate that although captopril is an effective antihypertensive agent, its action does not depend only on inhibition of plasma angiotensin I converting enzyme activity.", "contents": "Effect of captopril (SQ 14225) on blood pressure, plasma renin activity and angiotensin I converting enzyme activity. Seven patients with essential hypertension and seven patients with hypertension associated with renal artery stenosis received captopril (SQ 14225), an inhibitor of angiotensin I converting enzyme. There was a significant reduction in mean blood pressure, from 176/113 +/- 4/3 mm Hg during the control period to 140/90 +/- 5/3 mm Hg during captopril administration. Five patients received captopril alone and nine patients needed hydrochlorothiazide in addition to control their blood pressure. Captopril produced a significant increase in peripheral plasma renin activity. When measured 12 hours after the administration of captopril the angiotensin I converting enzyme activity was found to be similar to that during the control period even though the blood pressure was at or near normal. These findings indicate that although captopril is an effective antihypertensive agent, its action does not depend only on inhibition of plasma angiotensin I converting enzyme activity."}
{"id": "PMID:223758", "title": "Suspected reticuloendotheliosis in turkeys with cutaneous lesions reminiscent of fowl pox.", "content": "Twelve turkeys from a flock of 2,500 had cutaneous lesions somewhat resembling fowl pox. Lymphoid-like tumors were evident in livers and spleens. Closer examination of cutaneous lesions, and histopathological examinations indicated skin lesions were also infiltrative and not unlike reticuloendotheliosis. Electron micrographs revealed the presence of C-type virus particles.", "contents": "Suspected reticuloendotheliosis in turkeys with cutaneous lesions reminiscent of fowl pox. Twelve turkeys from a flock of 2,500 had cutaneous lesions somewhat resembling fowl pox. Lymphoid-like tumors were evident in livers and spleens. Closer examination of cutaneous lesions, and histopathological examinations indicated skin lesions were also infiltrative and not unlike reticuloendotheliosis. Electron micrographs revealed the presence of C-type virus particles."}
{"id": "PMID:223759", "title": "Differential protection of normal and malignant tissues against the cytotoxic effects of mechlorethamine.", "content": "The radioprotective drug, WR-2721 (S,2-[3-aminopropylamino]ethyl-phosphorothioic acid), has been studied in terms of its ability to (a) protect mice against mechlorethamine (HN2)-induced hematopoietic death, and (b) alter the ability of HN2 injections to induce growth delay in a solid tumor, the Line 1 lung carcinoma. When WR-2721 was injected ip 15 minutes before iv injections of HN2, it increased resistance to hematopoietic death by a factor of 2, and the protection declined with a half-life of 1.5-2.0 hours. Similar administration of both drugs failed to alter the responsiveness of the Line 1 lung carcinoma to HN2-induced growth delays, except when the HN2 was given within 15 minutes after WR-2721. This interaction of the two drugs, when given within 5-15 minutes of each other, does not appear to be true protection at the tumor site, but rather appears to result from HN2 inactivation in the blood. When HN2 is given 30-60 minutes after WR-2721, it is possible to obtain a twofold increase in the tumor delay without risking increased hematopoietic injury.", "contents": "Differential protection of normal and malignant tissues against the cytotoxic effects of mechlorethamine. The radioprotective drug, WR-2721 (S,2-[3-aminopropylamino]ethyl-phosphorothioic acid), has been studied in terms of its ability to (a) protect mice against mechlorethamine (HN2)-induced hematopoietic death, and (b) alter the ability of HN2 injections to induce growth delay in a solid tumor, the Line 1 lung carcinoma. When WR-2721 was injected ip 15 minutes before iv injections of HN2, it increased resistance to hematopoietic death by a factor of 2, and the protection declined with a half-life of 1.5-2.0 hours. Similar administration of both drugs failed to alter the responsiveness of the Line 1 lung carcinoma to HN2-induced growth delays, except when the HN2 was given within 15 minutes after WR-2721. This interaction of the two drugs, when given within 5-15 minutes of each other, does not appear to be true protection at the tumor site, but rather appears to result from HN2 inactivation in the blood. When HN2 is given 30-60 minutes after WR-2721, it is possible to obtain a twofold increase in the tumor delay without risking increased hematopoietic injury."}
{"id": "PMID:223760", "title": "Intra- and extracellular electrolytes and sarcolemmal ATPase in the failing heart due to pressure overload in dogs.", "content": "An investigation of changes in the Mg2+ -dependent, Na+ -K+ -stimulated sarcolemmal ATPase and of intracellular electrolytes in the left failing heart due to pressure overload (aortic banding) was carried out in dogs. There was no change in the sarcolemmal Mg2+ -ATPase of the left or right ventricle for the whole duration (3 to 9 months) of left ventricular pressure overload. In the early phase (3 months) of aortic banding, when there was no haemodynamic evidence of left ventricular failure, there was also no significant change in the sarcolemmal Na+ -K+ -ATPase, extracellular space, or intra- and extracellular electrolytes. However, during 6 to 9 months of aortic binding when there was haemodynamic evidence of left ventricular failure (increased end-diastolic pressure, decreased cardiac index and (dP/dt)/IIP, enlarged heart), there was also a marked increase in the left ventricular sarcolemmal Na+ -K+ -ATPase and intracellular K+; and a decrease in the intracellular Na+ and Ca2+. The extracellular space in the left ventricle also increased significantly. Unlike the left ventricle, the right ventricle did not show any evidence of failure, not did it show any change in the sarcolemmal Na+ -K+ -ATPase and intracellular electrolytes during any period of aortic banding. These results suggest that the decrease in the myocardial contractility in failing heart due to pressure overload might be associated with a decrease in the intracellular Ca2+ as a result of an increase in the sarcolemmal Na+ -K+ -ATPase.", "contents": "Intra- and extracellular electrolytes and sarcolemmal ATPase in the failing heart due to pressure overload in dogs. An investigation of changes in the Mg2+ -dependent, Na+ -K+ -stimulated sarcolemmal ATPase and of intracellular electrolytes in the left failing heart due to pressure overload (aortic banding) was carried out in dogs. There was no change in the sarcolemmal Mg2+ -ATPase of the left or right ventricle for the whole duration (3 to 9 months) of left ventricular pressure overload. In the early phase (3 months) of aortic banding, when there was no haemodynamic evidence of left ventricular failure, there was also no significant change in the sarcolemmal Na+ -K+ -ATPase, extracellular space, or intra- and extracellular electrolytes. However, during 6 to 9 months of aortic binding when there was haemodynamic evidence of left ventricular failure (increased end-diastolic pressure, decreased cardiac index and (dP/dt)/IIP, enlarged heart), there was also a marked increase in the left ventricular sarcolemmal Na+ -K+ -ATPase and intracellular K+; and a decrease in the intracellular Na+ and Ca2+. The extracellular space in the left ventricle also increased significantly. Unlike the left ventricle, the right ventricle did not show any evidence of failure, not did it show any change in the sarcolemmal Na+ -K+ -ATPase and intracellular electrolytes during any period of aortic banding. These results suggest that the decrease in the myocardial contractility in failing heart due to pressure overload might be associated with a decrease in the intracellular Ca2+ as a result of an increase in the sarcolemmal Na+ -K+ -ATPase."}
{"id": "PMID:223762", "title": "Morphological and physiological aspects of melanophores in primary culture from tadpoles of Xenopus laevis.", "content": "Melanophores from tadpoles of Xenopus laevis (Daudin) were isolated by digestion of tail fins with acetyltrypsin and collagenase and maintained in primary culture for 6 weeks up to 3 months. Within 36 to 72 h the melanophores develop one to eight dendritic processes per cell; secondary and tertiary branchings of the processes were frequently observed. The melanophores in primary culture disperse under the influence of alpha-MSH or cyclic AMP; upon rinsing out these substances the cells aggregate. In darkness, about 40% of the cells disperse their pigment, whereas under illumination the pigment of the melanophores aggregates. To date, attempts to initiate cell division in melanophores have not been successful.", "contents": "Morphological and physiological aspects of melanophores in primary culture from tadpoles of Xenopus laevis. Melanophores from tadpoles of Xenopus laevis (Daudin) were isolated by digestion of tail fins with acetyltrypsin and collagenase and maintained in primary culture for 6 weeks up to 3 months. Within 36 to 72 h the melanophores develop one to eight dendritic processes per cell; secondary and tertiary branchings of the processes were frequently observed. The melanophores in primary culture disperse under the influence of alpha-MSH or cyclic AMP; upon rinsing out these substances the cells aggregate. In darkness, about 40% of the cells disperse their pigment, whereas under illumination the pigment of the melanophores aggregates. To date, attempts to initiate cell division in melanophores have not been successful."}
{"id": "PMID:223763", "title": "Cyclic GMP and cyclic AMP changes in response to folic acid pulses during cell development of Dictyostelium discoideum.", "content": "Folic acid pulses induced developmental processes in agip 71, a morphogenetic mutant of Dictyostelium discoideum, strain Ax-2. Cells that had received folic acid pulses were able to form EDTA-stable cell aggregates and to complete full differentiation to fruiting bodies. In these cells no autonomous periodic activities were observed by light scattering. Folic acid pulses elicited increases in the concentrations of cyclic GMP and cyclic AMP. In undifferentiated cells, folic acid caused a rapid increase in the level of cyclic GMP without a significant change in the level of cyclic AMP. In an advanced developmental state folic acid caused an increase in cyclic AMP in addition to two successsive peaks of cyclic GMP. Experiments performed with the parent strain, Ax-2, also showed that during the development towards aggregation competence, cells acquired the ability to produce a cyclic AMP peak in response to folic acid.", "contents": "Cyclic GMP and cyclic AMP changes in response to folic acid pulses during cell development of Dictyostelium discoideum. Folic acid pulses induced developmental processes in agip 71, a morphogenetic mutant of Dictyostelium discoideum, strain Ax-2. Cells that had received folic acid pulses were able to form EDTA-stable cell aggregates and to complete full differentiation to fruiting bodies. In these cells no autonomous periodic activities were observed by light scattering. Folic acid pulses elicited increases in the concentrations of cyclic GMP and cyclic AMP. In undifferentiated cells, folic acid caused a rapid increase in the level of cyclic GMP without a significant change in the level of cyclic AMP. In an advanced developmental state folic acid caused an increase in cyclic AMP in addition to two successsive peaks of cyclic GMP. Experiments performed with the parent strain, Ax-2, also showed that during the development towards aggregation competence, cells acquired the ability to produce a cyclic AMP peak in response to folic acid."}
{"id": "PMID:223769", "title": "Metabolic alterations of liver regeneration. XV. Cadmium-mediated depression of thymidine and thymidylate kinase induction in rats.", "content": "Cadmium administered shortly before or after partial hepatectomy blocks in a dose-dependent manner the increase of thymidine and thymidylate kinase activities in regenerating rat livers. The effect of cadmium can be partially antagonized by simultaneous zinc administration. The intraperitoneal injection of cadmium is more effective than its subcutaneous administration. While there are in vitro differences in the sensitivity of thymidine kinase and thymidylate kinase towards Cd2+-, Zn2%- and Cu2+-ions, both enzymes are equally depressed following their in vivo administration. Cadmium displays the highest inhibitory activity and resembles in this respect beryllium [1].", "contents": "Metabolic alterations of liver regeneration. XV. Cadmium-mediated depression of thymidine and thymidylate kinase induction in rats. Cadmium administered shortly before or after partial hepatectomy blocks in a dose-dependent manner the increase of thymidine and thymidylate kinase activities in regenerating rat livers. The effect of cadmium can be partially antagonized by simultaneous zinc administration. The intraperitoneal injection of cadmium is more effective than its subcutaneous administration. While there are in vitro differences in the sensitivity of thymidine kinase and thymidylate kinase towards Cd2+-, Zn2%- and Cu2+-ions, both enzymes are equally depressed following their in vivo administration. Cadmium displays the highest inhibitory activity and resembles in this respect beryllium [1]."}
{"id": "PMID:223770", "title": "Cyclic nucleotides levels in the liver of rats treated with CCl4.", "content": "Treatment of rats with two different doses of CCl4 (respectively 2.5 and 0.5 ml/kg body wt. intragastrically) is followed by a rapid increase in the cAMP content of the liver. With 0.5 ml of CCl4, the increase occurs as early as 30 min after poisoning, namely about 4-5 h before the onset of triglyceride accumulation in the liver. The maximum increase has been at 6 h after administration of the hepatotoxin. In both experimental conditions, normal values are recovered only after 36-48 h. cGMP level appears unmodified during the whole observation period. Therefore the ratio cGMP/CAMP decreases consistently. The ATP level decreases significantly between 2 and 12 h. The increase in liver triglycerides level after CCl4 can be also a consequence of an impairment of microtubule function, leading to a decreased release of lipoprotein micelles from hepatocytes into the blood stream.", "contents": "Cyclic nucleotides levels in the liver of rats treated with CCl4. Treatment of rats with two different doses of CCl4 (respectively 2.5 and 0.5 ml/kg body wt. intragastrically) is followed by a rapid increase in the cAMP content of the liver. With 0.5 ml of CCl4, the increase occurs as early as 30 min after poisoning, namely about 4-5 h before the onset of triglyceride accumulation in the liver. The maximum increase has been at 6 h after administration of the hepatotoxin. In both experimental conditions, normal values are recovered only after 36-48 h. cGMP level appears unmodified during the whole observation period. Therefore the ratio cGMP/CAMP decreases consistently. The ATP level decreases significantly between 2 and 12 h. The increase in liver triglycerides level after CCl4 can be also a consequence of an impairment of microtubule function, leading to a decreased release of lipoprotein micelles from hepatocytes into the blood stream."}
{"id": "PMID:223772", "title": "[Activation of the pituitary-adrenal axis by nipple suction in the lactating rat].", "content": "The response of the pituitary-adrenal axis to suckling in lactating Rats is dependent on two factors: 1. a psychic factor, which is identical by its effects to the psychological stress of the strange environment (transitory increase of plasma corticosterone and no significant modification of the content of ACTH in the two lobes of the pituitary); 2. a specific factor namely the stimulation of the nipples, which is distinguishable from the psychic factor by a longer release of corticosterone by the adrenals and a durable and significant decrease of the content of ACTH in the pars distalis.", "contents": "[Activation of the pituitary-adrenal axis by nipple suction in the lactating rat]. The response of the pituitary-adrenal axis to suckling in lactating Rats is dependent on two factors: 1. a psychic factor, which is identical by its effects to the psychological stress of the strange environment (transitory increase of plasma corticosterone and no significant modification of the content of ACTH in the two lobes of the pituitary); 2. a specific factor namely the stimulation of the nipples, which is distinguishable from the psychic factor by a longer release of corticosterone by the adrenals and a durable and significant decrease of the content of ACTH in the pars distalis."}
{"id": "PMID:223773", "title": "[Role of tropomyosin in the sensitivity of (Na+ + K+) ATPase to ouabain].", "content": "EDTA treatment of isolated plasma membranes from MF2S cells increased 1,000 fold the sensitivity of (Na+ + K+) ATPase activity to ouabain. The original sensitivity of the enzyme to the drug is recovered after addition of tropomyosin together with Ca++ ions to the treated membranes.", "contents": "[Role of tropomyosin in the sensitivity of (Na+ + K+) ATPase to ouabain]. EDTA treatment of isolated plasma membranes from MF2S cells increased 1,000 fold the sensitivity of (Na+ + K+) ATPase activity to ouabain. The original sensitivity of the enzyme to the drug is recovered after addition of tropomyosin together with Ca++ ions to the treated membranes."}
{"id": "PMID:223774", "title": "[Molecular forms of human leukocytic alpha-galactosidase and N-acetyl-alpha-galactosaminidase].", "content": "1. Normal human leukocytes present three molecular forms of alpha-galactosidase (EC 3.2.1.22) separated using electrofocusing: a new major form IV (pI 4.0) characteristic of leukocytes and two forms that exist in other tissues, form I (pI 4.5) and form II (pI 4.0). 2. Normal human leukocytes present only one molecular form (pI 4.5) of N-acetyl-alpha-galactosaminidase (EC 3.2.1.49) corresponding to alpha-galactosidase form II. 3. In leukocytes from patients with Fabry disease, the electrofocusing shows that the alpha-galactosidase lacking corresponds to forms I and IV, while the residual activity corresponds to form II (or N-acetyl-alpha-galactosaminidase).", "contents": "[Molecular forms of human leukocytic alpha-galactosidase and N-acetyl-alpha-galactosaminidase]. 1. Normal human leukocytes present three molecular forms of alpha-galactosidase (EC 3.2.1.22) separated using electrofocusing: a new major form IV (pI 4.0) characteristic of leukocytes and two forms that exist in other tissues, form I (pI 4.5) and form II (pI 4.0). 2. Normal human leukocytes present only one molecular form (pI 4.5) of N-acetyl-alpha-galactosaminidase (EC 3.2.1.49) corresponding to alpha-galactosidase form II. 3. In leukocytes from patients with Fabry disease, the electrofocusing shows that the alpha-galactosidase lacking corresponds to forms I and IV, while the residual activity corresponds to form II (or N-acetyl-alpha-galactosaminidase)."}
{"id": "PMID:223776", "title": "[Choice of a spin label probe in order to study the recombination of beta-hydroxybutyrate dehydrogenase of a rat liver inner mitochondrial membrane with lecithin vesicles].", "content": "We find from studying the inhibitory effect of N-ethylmaleimide (NEM) on the enzymatic activity of beta-hydroxybutyrate dehydrogenase, that approximately one molecule of NEM is bound for one molecule of protein when the enzymatic activity is completely inhibited. Since the protein is a dimer this implies that each molecule of protein possesses only one thiol group in its catalytic center. Two long chain maleimide derivates: (10.3) NEM and (1.14) NEM conform, if a reasonable assumption is accepted to the conditions required for the study of the recombination of beta-hydroxybutyrate dehydrogenase with lecithin vesicles by spin label technique.", "contents": "[Choice of a spin label probe in order to study the recombination of beta-hydroxybutyrate dehydrogenase of a rat liver inner mitochondrial membrane with lecithin vesicles]. We find from studying the inhibitory effect of N-ethylmaleimide (NEM) on the enzymatic activity of beta-hydroxybutyrate dehydrogenase, that approximately one molecule of NEM is bound for one molecule of protein when the enzymatic activity is completely inhibited. Since the protein is a dimer this implies that each molecule of protein possesses only one thiol group in its catalytic center. Two long chain maleimide derivates: (10.3) NEM and (1.14) NEM conform, if a reasonable assumption is accepted to the conditions required for the study of the recombination of beta-hydroxybutyrate dehydrogenase with lecithin vesicles by spin label technique."}
{"id": "PMID:223777", "title": "A prospective study of respiratory infection in adult asthmatics and their normal spouses.", "content": "A prospective study of respiratory infections was performed in nineteen married asthmatics and their normal spouses who were examined at monthly intervals during a 1-year period. The colds described were associated with nasal symptoms, sore throat and usually malaise, fever, cough and hoarseness. The asthamtics reported a larger number of these symptomatic episodes than the non-asthmatics but significantly fewer of the episodes in the asthmatics were objectively confirmed by viral isolation or rise in serum titre of viral antibody. The frequency of respiratory infections was not influenced by the long term use of inhaled beclomethasone dipropionate and oral corticosteroid drugs. Less than 10% of the exacerbations of asthma were associated with respiratory infection. The disability resulting from respiratory infections in the asthmatics did not significantly exceed that in the non-asthmatics.", "contents": "A prospective study of respiratory infection in adult asthmatics and their normal spouses. A prospective study of respiratory infections was performed in nineteen married asthmatics and their normal spouses who were examined at monthly intervals during a 1-year period. The colds described were associated with nasal symptoms, sore throat and usually malaise, fever, cough and hoarseness. The asthamtics reported a larger number of these symptomatic episodes than the non-asthmatics but significantly fewer of the episodes in the asthmatics were objectively confirmed by viral isolation or rise in serum titre of viral antibody. The frequency of respiratory infections was not influenced by the long term use of inhaled beclomethasone dipropionate and oral corticosteroid drugs. Less than 10% of the exacerbations of asthma were associated with respiratory infection. The disability resulting from respiratory infections in the asthmatics did not significantly exceed that in the non-asthmatics."}
{"id": "PMID:223778", "title": "Liquid-chromatographic assay for urinary 3-methoxy-4-hydroxymandelic acid, with use of a periodate oxidative monitor.", "content": "We describe a \"high-performance\" liquid-chromatographic procedure for measuring 3-methoxy-4-hydroxymandelic acid (vanillylmandelic acid) in urine. The compound is quantitatively extracted from urine by use of an automated system, including an anion-exchange resin. After elution from the resin and concentration by air drying, the urine extract is chromatographed on an octyl silica column, with use of a buffered mobile phase. To overcome interference from other organic acid in the extract, the column effluent is reacted with periodate in an analytical system to oxidize the analyte and internal standard to products that absorb at 360 nm. We evaluated the procedure for precision, linearity, analytical recovery, interfering substances, and correlation with an established procedure. The combination of a preliminary resin extraction, a liquid-chromatographic separation, and a periodate oxidative monitor results in a rapid, specific method that can be adapted for use in the clinical laboratory.", "contents": "Liquid-chromatographic assay for urinary 3-methoxy-4-hydroxymandelic acid, with use of a periodate oxidative monitor. We describe a \"high-performance\" liquid-chromatographic procedure for measuring 3-methoxy-4-hydroxymandelic acid (vanillylmandelic acid) in urine. The compound is quantitatively extracted from urine by use of an automated system, including an anion-exchange resin. After elution from the resin and concentration by air drying, the urine extract is chromatographed on an octyl silica column, with use of a buffered mobile phase. To overcome interference from other organic acid in the extract, the column effluent is reacted with periodate in an analytical system to oxidize the analyte and internal standard to products that absorb at 360 nm. We evaluated the procedure for precision, linearity, analytical recovery, interfering substances, and correlation with an established procedure. The combination of a preliminary resin extraction, a liquid-chromatographic separation, and a periodate oxidative monitor results in a rapid, specific method that can be adapted for use in the clinical laboratory."}
{"id": "PMID:223779", "title": "Comparison of current methods for high-density lipoprotein cholesterol quantitation.", "content": "We compared six precipitation methods for high-density-lipoprotein cholesterol quantitation with an ultracentrifugation method, the accuracy of which was improved by correcting for 4% manipulative loss in the d greater than 1.063 fractions. For purposes of comparison, the apoprotein B-associated cholesterol (average 56 mg/L) measured by immunoassay in the d greater than 1.063 fractions was subtracted. In 65 plasma samples from men, women, and children, a heparin-Mn2+ procedure with Mn2+ at 46 mmol/L produced results slightly higher (+16 mg/L), while results with Mn2+ at 92 mmol/L averaged slightly lower (-8 mg/L) than the comparison ultracentrifuge method. Results that were about 5% low were obtained by the dextran sulfate 500-Mg2+ (-25 mg/L) and phosphotungstate-Mg2+ (-31 mg/L) methods. A heparin-Ca2+ method produced results 10% high (+58 mg/L). Results by a polyethylene glycol-6000 precipitation method were 12% low (-64 mg/L). Precision was better with the two heparin-Mn2+ and the dextran sulfate 500-Mg2+ procedures, with CVs of 4%, intermediate with phosphotungstate-Mg2+ and polyethylene glycol-6000 (CV 6-7%), and poorest with heparin-Ca2+ (CV 10%). Precipitation by phosphotungate-Mg2+ appeared more sensitive to reagent concentration and temperature variations than either the heparin-Mn2+ or dextran sulfate 500-Mg2+ methods. We conclude that these precipitation methods are not equivalent, but give rise to significant systematic differences in high-density-lipoprotein cholesterol quantitation.", "contents": "Comparison of current methods for high-density lipoprotein cholesterol quantitation. We compared six precipitation methods for high-density-lipoprotein cholesterol quantitation with an ultracentrifugation method, the accuracy of which was improved by correcting for 4% manipulative loss in the d greater than 1.063 fractions. For purposes of comparison, the apoprotein B-associated cholesterol (average 56 mg/L) measured by immunoassay in the d greater than 1.063 fractions was subtracted. In 65 plasma samples from men, women, and children, a heparin-Mn2+ procedure with Mn2+ at 46 mmol/L produced results slightly higher (+16 mg/L), while results with Mn2+ at 92 mmol/L averaged slightly lower (-8 mg/L) than the comparison ultracentrifuge method. Results that were about 5% low were obtained by the dextran sulfate 500-Mg2+ (-25 mg/L) and phosphotungstate-Mg2+ (-31 mg/L) methods. A heparin-Ca2+ method produced results 10% high (+58 mg/L). Results by a polyethylene glycol-6000 precipitation method were 12% low (-64 mg/L). Precision was better with the two heparin-Mn2+ and the dextran sulfate 500-Mg2+ procedures, with CVs of 4%, intermediate with phosphotungstate-Mg2+ and polyethylene glycol-6000 (CV 6-7%), and poorest with heparin-Ca2+ (CV 10%). Precipitation by phosphotungate-Mg2+ appeared more sensitive to reagent concentration and temperature variations than either the heparin-Mn2+ or dextran sulfate 500-Mg2+ methods. We conclude that these precipitation methods are not equivalent, but give rise to significant systematic differences in high-density-lipoprotein cholesterol quantitation."}
{"id": "PMID:223782", "title": "A direct radio-immunoassay for plasma delta 4-androstenedione. Application to children.", "content": "A RIA for the estimation of delta 4-androstenedione in human plasma without chromatographic purification is analyzed. Sensitivity, accuracy, precision and specificity are shown to be, at least, equivalent to those of methods involving chromatography.", "contents": "A direct radio-immunoassay for plasma delta 4-androstenedione. Application to children. A RIA for the estimation of delta 4-androstenedione in human plasma without chromatographic purification is analyzed. Sensitivity, accuracy, precision and specificity are shown to be, at least, equivalent to those of methods involving chromatography."}
{"id": "PMID:223784", "title": "A major locus for hyper-beta-lipoproteinemia with xanthomatosis.", "content": "Complex segregation analysis of hyper-beta-lipoproteinemia with xanthomatosis has provided strong evidence for a major locus, in addition to significant polygenic effect and sibling environment. Estimates of gene frequency agree with values generally given in the literature.", "contents": "A major locus for hyper-beta-lipoproteinemia with xanthomatosis. Complex segregation analysis of hyper-beta-lipoproteinemia with xanthomatosis has provided strong evidence for a major locus, in addition to significant polygenic effect and sibling environment. Estimates of gene frequency agree with values generally given in the literature."}
{"id": "PMID:223786", "title": "Effect of veratrum alkaloids on right and left atrial receptors in the cat.", "content": "1. The effects of veriloid and veratridine on right and left atrial receptors have been studied in cats. 2. Threshold doses of these drugs for right atrial receptors were found to be almost twice those for left atrial receptors. Beyond threshold doses, however, the dose-response curves were similar. 3. The sensitivity of left atrial receptors to veratridine was not altered by an increase in PCO2 and/or decrease in PO2 of left atrial blood. Therefore, the difference in the behaviour of left and right atrial receptors to these drugs is not due to the differences in PO2 and PCO2 of blood in the two atria. They are more likely to be a feature of the regenerative  regions of the receptors.", "contents": "Effect of veratrum alkaloids on right and left atrial receptors in the cat. 1. The effects of veriloid and veratridine on right and left atrial receptors have been studied in cats. 2. Threshold doses of these drugs for right atrial receptors were found to be almost twice those for left atrial receptors. Beyond threshold doses, however, the dose-response curves were similar. 3. The sensitivity of left atrial receptors to veratridine was not altered by an increase in PCO2 and/or decrease in PO2 of left atrial blood. Therefore, the difference in the behaviour of left and right atrial receptors to these drugs is not due to the differences in PO2 and PCO2 of blood in the two atria. They are more likely to be a feature of the regenerative  regions of the receptors."}
{"id": "PMID:223793", "title": "Tumours at the spinocranial junction: some clinical and electromyographic aspects in relation to the symptomatology.", "content": "On the basis of six cases of a tumour at the spinocranial junction, the clinical symptomatology is discussed with special reference to the occurrence of astereognosis and amyotrophy of the hand muscles. Possible mechanisms underlying these symptoms are discussed. In the authors' opinion, the frequent association of these symptoms is explained by the association of two pathogenic mechanisms, i.e., compression of the posterior column or interference with the arterial blood flow to the medial lemniscus, leading to astereognosis, and interference with the venous blood flow, leading to amyotrophy of the hand muscles.", "contents": "Tumours at the spinocranial junction: some clinical and electromyographic aspects in relation to the symptomatology. On the basis of six cases of a tumour at the spinocranial junction, the clinical symptomatology is discussed with special reference to the occurrence of astereognosis and amyotrophy of the hand muscles. Possible mechanisms underlying these symptoms are discussed. In the authors' opinion, the frequent association of these symptoms is explained by the association of two pathogenic mechanisms, i.e., compression of the posterior column or interference with the arterial blood flow to the medial lemniscus, leading to astereognosis, and interference with the venous blood flow, leading to amyotrophy of the hand muscles."}
{"id": "PMID:223794", "title": "Subacute combined degeneration of the spinal cord and the vitamin B12 metabolism, a clinical study.", "content": "In 28 patients suffering from subacute combined degeneration of the spinal cord, vitamin B12 metabolism was investigated. Two postulates, proving vitamin B12 deficiency and excluding another cause for the clinical symptoms, have to be fulfilled. Two patients had no disturbance in their vitamin B12 metabolism. Seven patients had a distinct vitamin B12 deficiency. In the remaining 19 patients we found a mild vitamin B12 deficiency. Of these patients, 5 had had a subtotal gastrectomy, one had had a low absorption of vitamin B12, and 13 patients we could not find a distinct cause for the vitamin B12 deficiency. It is not impossible that nutritional habits can be hold responsible for this deficiency. The question whether these 13 patients should be treated with vitamin B12 for the rest of their lives is difficult to answer. It is a conditio sine qua non that in the patients with S.C.D. the vitamin B12 metabolism is examined circumstantially. By so doing, it may be possible to detect, in cases with minor clinical signs and symptoms of S.C.D., the cause of their illness.", "contents": "Subacute combined degeneration of the spinal cord and the vitamin B12 metabolism, a clinical study. In 28 patients suffering from subacute combined degeneration of the spinal cord, vitamin B12 metabolism was investigated. Two postulates, proving vitamin B12 deficiency and excluding another cause for the clinical symptoms, have to be fulfilled. Two patients had no disturbance in their vitamin B12 metabolism. Seven patients had a distinct vitamin B12 deficiency. In the remaining 19 patients we found a mild vitamin B12 deficiency. Of these patients, 5 had had a subtotal gastrectomy, one had had a low absorption of vitamin B12, and 13 patients we could not find a distinct cause for the vitamin B12 deficiency. It is not impossible that nutritional habits can be hold responsible for this deficiency. The question whether these 13 patients should be treated with vitamin B12 for the rest of their lives is difficult to answer. It is a conditio sine qua non that in the patients with S.C.D. the vitamin B12 metabolism is examined circumstantially. By so doing, it may be possible to detect, in cases with minor clinical signs and symptoms of S.C.D., the cause of their illness."}
{"id": "PMID:223795", "title": "Benign tumors of the cranial vault, a report of 12 cases.", "content": "Twelve cases of different types of benign tumors of the cranial vault are described. In most cases there was a localised swelling which was sometimes painful. There were no neurological abnormalities due to the lesion. Radiological examination revealed a zone of radiolucency in all cases. In 8 patients the brain scan with 99mTc sodiumpertechnetate showed an increased uptake at the level of the bone lesion. Eight patients were operated upon and a total resection could be performed. In the four others only a biopsy was done. Histopathological examination revealed a fibrous dysplasia (3x), an eosinophilic granuloma (3x), an osteoid osteoma (2x), a cholesteatoma, aneurysmal bone cyst, an osteoclastoma and a fibroma. The pathological mechanisms underlying these different lesions are discussed.", "contents": "Benign tumors of the cranial vault, a report of 12 cases. Twelve cases of different types of benign tumors of the cranial vault are described. In most cases there was a localised swelling which was sometimes painful. There were no neurological abnormalities due to the lesion. Radiological examination revealed a zone of radiolucency in all cases. In 8 patients the brain scan with 99mTc sodiumpertechnetate showed an increased uptake at the level of the bone lesion. Eight patients were operated upon and a total resection could be performed. In the four others only a biopsy was done. Histopathological examination revealed a fibrous dysplasia (3x), an eosinophilic granuloma (3x), an osteoid osteoma (2x), a cholesteatoma, aneurysmal bone cyst, an osteoclastoma and a fibroma. The pathological mechanisms underlying these different lesions are discussed."}
{"id": "PMID:223796", "title": "Vertebral osteomyelitis and epidural abcess due to mucormycosis, a case report.", "content": "A patient is described, with a history of pain in the neck, followed by a slowly progressive loss of muscle strength in both arms, followed by tetraplegia. Medical history included laryngectomy with partial hypopharyngectomy preceded by radiotherapy, because of carcinoma. X-ray of the cervical spine was suggestive for metastases. The patient died as a consequence of massive pulmonary embolism and at autopsy the cause of the neurological deficit turned out to be vertebral osteomyelitis and epidural abscess due to mucormycosis.", "contents": "Vertebral osteomyelitis and epidural abcess due to mucormycosis, a case report. A patient is described, with a history of pain in the neck, followed by a slowly progressive loss of muscle strength in both arms, followed by tetraplegia. Medical history included laryngectomy with partial hypopharyngectomy preceded by radiotherapy, because of carcinoma. X-ray of the cervical spine was suggestive for metastases. The patient died as a consequence of massive pulmonary embolism and at autopsy the cause of the neurological deficit turned out to be vertebral osteomyelitis and epidural abscess due to mucormycosis."}
{"id": "PMID:223798", "title": "Vertebrobasilar insufficiency due to Tumoural emboli.", "content": "A case, which is clinically characterized by a subacute vertebrobasilar syndrome, is presented. The necropsy reveals multiple infarcts in brainstem, cerebellum and left cerebral hemisphere, due to tumoural emboli of a non-detected primary tumour. It is postulated that the latter has to originate in the lungs in order to produce this unique type of cerebral arterial embolism.", "contents": "Vertebrobasilar insufficiency due to Tumoural emboli. A case, which is clinically characterized by a subacute vertebrobasilar syndrome, is presented. The necropsy reveals multiple infarcts in brainstem, cerebellum and left cerebral hemisphere, due to tumoural emboli of a non-detected primary tumour. It is postulated that the latter has to originate in the lungs in order to produce this unique type of cerebral arterial embolism."}
{"id": "PMID:223799", "title": "Cerebrospinal fluid glutamine levels and EEG findings in patients with hepatic encephalopathy.", "content": "The cerebrospinal fluid glutamine level was determined and an electro-encephalogram was made at roughly the same time in 41 patients on 55 occasions. A modified electro-encephalographic grading for practical use was introduced, because the classical electroencephalographic grading described by PARSONS-SMITH et al. (1957) does not apply to patients in deep coma. A significant correlation was found between the natural logarithms of cerebrospinal fluid glutamine levels and the electro-encephalic grade. In combination, these parameters provide valuable diagnostic and prognostic information in hepatic encephalopathy, and each can serve separately for follow-up purposes.", "contents": "Cerebrospinal fluid glutamine levels and EEG findings in patients with hepatic encephalopathy. The cerebrospinal fluid glutamine level was determined and an electro-encephalogram was made at roughly the same time in 41 patients on 55 occasions. A modified electro-encephalographic grading for practical use was introduced, because the classical electroencephalographic grading described by PARSONS-SMITH et al. (1957) does not apply to patients in deep coma. A significant correlation was found between the natural logarithms of cerebrospinal fluid glutamine levels and the electro-encephalic grade. In combination, these parameters provide valuable diagnostic and prognostic information in hepatic encephalopathy, and each can serve separately for follow-up purposes."}
{"id": "PMID:223802", "title": "Grey scale ultrasound appearances in hepatocellular carcinoma.", "content": "Thirty patients with histologically proven hepatocellular carcinoma were examined ultrasonically. All except two of these cases were reported ultrasonically as having a solid mass. Forty-three per cent of these lesions appeared multiple and 90% had irregular walls or boundaries. Stretching or distortion of the inferior margin of the liver is considered significant and 53% of cases demonstrated this feature. Just over two-thirds (67%) of the lesions were echogenic and under one-third (27%) were mixed lesions with echogenic and transonic areas. These transonic areas are considered to be due to the necrosis within the tumour. Most patients presented late and died within three months. Ninety per cent had clinical hepatomegaly or an epigastric mass. So far the main benefits of ultrasonography have been the recognition or exclusion of treatable disease such as liver abscess, cysts and congestive conditions of the liver, which may also present with unexplained hepatomegaly or epigastric masses. The possibility of a recognisable echo pattern for hepatocellular carcinoma emerged from this study. By conducting selective ultrasonic surveys in endemic areas and by employing the ultrasonic criteria described early diagnosis may be possible. Aspects of management and research may be assisted.", "contents": "Grey scale ultrasound appearances in hepatocellular carcinoma. Thirty patients with histologically proven hepatocellular carcinoma were examined ultrasonically. All except two of these cases were reported ultrasonically as having a solid mass. Forty-three per cent of these lesions appeared multiple and 90% had irregular walls or boundaries. Stretching or distortion of the inferior margin of the liver is considered significant and 53% of cases demonstrated this feature. Just over two-thirds (67%) of the lesions were echogenic and under one-third (27%) were mixed lesions with echogenic and transonic areas. These transonic areas are considered to be due to the necrosis within the tumour. Most patients presented late and died within three months. Ninety per cent had clinical hepatomegaly or an epigastric mass. So far the main benefits of ultrasonography have been the recognition or exclusion of treatable disease such as liver abscess, cysts and congestive conditions of the liver, which may also present with unexplained hepatomegaly or epigastric masses. The possibility of a recognisable echo pattern for hepatocellular carcinoma emerged from this study. By conducting selective ultrasonic surveys in endemic areas and by employing the ultrasonic criteria described early diagnosis may be possible. Aspects of management and research may be assisted."}
{"id": "PMID:223803", "title": "The CT scan and subtraction angiography in chemodectomas.", "content": "The value of subtraction angiography and CT scanning in the diagnosis of chemodectomas are illustrated by two cases, a glomus jugulare tumour which exhibited true malignant behaviour, and a carotid body tumour. The characteristic early arterial blush of a chemodectoma, which can be obscured by bone, is clearly seen following subtraction techniques revealing tumours as small as 0.5 cm. The chemodectoma appeared as an isodense tumour on the CT scan with uniform contrast enhancement and well-defined margins. The appearances, however, are not diagnostic of a chemodectoma and may be simulated by other tumours.", "contents": "The CT scan and subtraction angiography in chemodectomas. The value of subtraction angiography and CT scanning in the diagnosis of chemodectomas are illustrated by two cases, a glomus jugulare tumour which exhibited true malignant behaviour, and a carotid body tumour. The characteristic early arterial blush of a chemodectoma, which can be obscured by bone, is clearly seen following subtraction techniques revealing tumours as small as 0.5 cm. The chemodectoma appeared as an isodense tumour on the CT scan with uniform contrast enhancement and well-defined margins. The appearances, however, are not diagnostic of a chemodectoma and may be simulated by other tumours."}
{"id": "PMID:223807", "title": "Correlation between volumetric CT imaging and autopsy measurements of glioblastoma size.", "content": "A three-dimensional reconstruction and display technique (THREAD SYSTEM) for serial computed tomography (CT) was employed in monitoring tumor volumes in two children under chemotherapy for glioblastoma multiforme of the cerebral hemispheres. Progressive diminution of tumor bulk was documented in the first patient and an increase in volume in the second. The first patient expired of the complications of his therapy and the second of transtentorial herniation. Independent measurements of the tumors as determined by a CT scan near the times of death and tumor dimensions measured at autopsy revealed good correlations between the radiographic and the anatomical data. The final CT measurement of tumor volume of 20 cm3 compared with an autopsy calculation of 13.3 cm3 in the first case. In the second case, CT volume was 417 cm3 and the actual volume of the primary tumor mass at autopsy was 437 cm3. The results suggest that the THREAD system is a practical method for monitoring the results of radiotherapy and chemotherapy in certain types of cerebral neoplasms.", "contents": "Correlation between volumetric CT imaging and autopsy measurements of glioblastoma size. A three-dimensional reconstruction and display technique (THREAD SYSTEM) for serial computed tomography (CT) was employed in monitoring tumor volumes in two children under chemotherapy for glioblastoma multiforme of the cerebral hemispheres. Progressive diminution of tumor bulk was documented in the first patient and an increase in volume in the second. The first patient expired of the complications of his therapy and the second of transtentorial herniation. Independent measurements of the tumors as determined by a CT scan near the times of death and tumor dimensions measured at autopsy revealed good correlations between the radiographic and the anatomical data. The final CT measurement of tumor volume of 20 cm3 compared with an autopsy calculation of 13.3 cm3 in the first case. In the second case, CT volume was 417 cm3 and the actual volume of the primary tumor mass at autopsy was 437 cm3. The results suggest that the THREAD system is a practical method for monitoring the results of radiotherapy and chemotherapy in certain types of cerebral neoplasms."}
{"id": "PMID:223811", "title": "Cadmium nephropathy.", "content": "Cadmium is an inessential trace metal which accumulates in human tissues from contamination of food, water or air. The kidney is the critical organ following long-term, low-level absorption either by inhalation or ingestion; accumulation occurring in tubular epithelium in the form of a cadmium-metallothionein complex, giving rise to tubular dysfunction. In a group of 12 cadmium workers some of whom were followed for up to 16 years, tubular proteinuria, renal glycosuria, aminoaciduria, hypercalciuria and defects of concentration and acidification have been observed. Two men became recurrent renal stone formers and 1 man, who had nephrocalcinosis when first seen, later developed vitamin D-resistant osteomalacia. Renal tubular dysfunction following cadmium exposure may continue symptom-free for long intervals, but in a proportion of cases serious clinical effects may eventually develop.", "contents": "Cadmium nephropathy. Cadmium is an inessential trace metal which accumulates in human tissues from contamination of food, water or air. The kidney is the critical organ following long-term, low-level absorption either by inhalation or ingestion; accumulation occurring in tubular epithelium in the form of a cadmium-metallothionein complex, giving rise to tubular dysfunction. In a group of 12 cadmium workers some of whom were followed for up to 16 years, tubular proteinuria, renal glycosuria, aminoaciduria, hypercalciuria and defects of concentration and acidification have been observed. Two men became recurrent renal stone formers and 1 man, who had nephrocalcinosis when first seen, later developed vitamin D-resistant osteomalacia. Renal tubular dysfunction following cadmium exposure may continue symptom-free for long intervals, but in a proportion of cases serious clinical effects may eventually develop."}
{"id": "PMID:223812", "title": "Canine viral enteritis. I. Status report on corona- and parvo-like viral enteritides.", "content": "This report attempts to provide the most recent information on salient features of two newly recognized viral enteritides of dogs. The viruses, a corona-like virus and canine parvo-like virus, are distinct but the disease manifestations in a particular outbreak often are similar. Laboratory study is therefore required. The parvoviral infection generally is more severe, with leukopenia (relative lymphopenia) a most prominent feature. Knowledge of the pathogenesis, epizootiology and the host's immune response is fragmentary at the present time, but research now in progress will doubtless expand knowledge of both diseases and of the viruses that cause them.", "contents": "Canine viral enteritis. I. Status report on corona- and parvo-like viral enteritides. This report attempts to provide the most recent information on salient features of two newly recognized viral enteritides of dogs. The viruses, a corona-like virus and canine parvo-like virus, are distinct but the disease manifestations in a particular outbreak often are similar. Laboratory study is therefore required. The parvoviral infection generally is more severe, with leukopenia (relative lymphopenia) a most prominent feature. Knowledge of the pathogenesis, epizootiology and the host's immune response is fragmentary at the present time, but research now in progress will doubtless expand knowledge of both diseases and of the viruses that cause them."}
{"id": "PMID:223813", "title": "Fluorescence mapping of mitochondrial redox changes in heart and brain.", "content": "Fluorescence techniques may be utilized to map changes in the distribution of mitochondrial redox states in heart and brain during ischemic or hypoxic stress. The basis of these techniques is the intrinsic fluorescence of reduced NADH and oxidized flavoprotein in mitochondria which respond to changes in critical oxygen supply. Ischemic areas in rabbit hearts induced by coronary ligation were detected and mapped based on the increase in NADH fluorescence in the ischemic zone. The width of the jeopardized normoxic tissue surrounding the ischemic area (less than 50--350 mu) was measured by combination of fluorescein angiography and NADH fluorescence. Areas of increased NADH fluorescence in gerbil brains after carotid artery ligation or induction of spreading depression were mapped in a similar manner. Intraoperative monitoring of flavoprotein fluorescence from human cerebral cortex after superficial temporal artery middle cerebral artery (STA-MCA) anastomoses demonstrated increased rates of cortical oxidative metabolism after the surgical procedures.", "contents": "Fluorescence mapping of mitochondrial redox changes in heart and brain. Fluorescence techniques may be utilized to map changes in the distribution of mitochondrial redox states in heart and brain during ischemic or hypoxic stress. The basis of these techniques is the intrinsic fluorescence of reduced NADH and oxidized flavoprotein in mitochondria which respond to changes in critical oxygen supply. Ischemic areas in rabbit hearts induced by coronary ligation were detected and mapped based on the increase in NADH fluorescence in the ischemic zone. The width of the jeopardized normoxic tissue surrounding the ischemic area (less than 50--350 mu) was measured by combination of fluorescein angiography and NADH fluorescence. Areas of increased NADH fluorescence in gerbil brains after carotid artery ligation or induction of spreading depression were mapped in a similar manner. Intraoperative monitoring of flavoprotein fluorescence from human cerebral cortex after superficial temporal artery middle cerebral artery (STA-MCA) anastomoses demonstrated increased rates of cortical oxidative metabolism after the surgical procedures."}
{"id": "PMID:223815", "title": "Oncornavirus modification of the Golgi apparatus.", "content": "Two virus system, The Friend leukaemia virus (FLV) and the Rous sarcoma virus (RSV), were introduced into tissue both in vitro and in vivo. Both brought about substantial modification of the activity of the Golgi apparatus detectable as such by specific radioautographic studies. This modification was accompanied by changes in the development and social behaviour of the cells with some differences being detectable between the in vivo and in vitro studies.", "contents": "Oncornavirus modification of the Golgi apparatus. Two virus system, The Friend leukaemia virus (FLV) and the Rous sarcoma virus (RSV), were introduced into tissue both in vitro and in vivo. Both brought about substantial modification of the activity of the Golgi apparatus detectable as such by specific radioautographic studies. This modification was accompanied by changes in the development and social behaviour of the cells with some differences being detectable between the in vivo and in vitro studies."}
{"id": "PMID:223816", "title": "Paracrystalline inclusions in various isolates of the blue-green bacteria Nostoc and Anabaena.", "content": "A number of different crystalline inclusions were observed in various isolates of Anabaena and Nostoc. Membrane-limited crystalline bodies were observed in 7 of 20 isolates of Anabaena and 19 of 29 isolates of Nostoc. These are spherical, single membrane-limited bodies from 0.6 to 0.1 micron in diameter. In most of the isolates they contained needle-like crystals 20 A in thickness and up to 80 nm in length. In 9 of the isolates the inclusions contained granular and fibrillar material. The number of bodies per cell varied in the different isolates from only a few, observed in many sections, up to 5 in a single section of A. subtropica (B1618). Crystalloids were observed in the cytoplasm of Anabaena sp. (1551), N. calcicola (B382), Nostoc sp. (588), and N. punctiforme (1629). In Anabaena sp. (1551) the roughly cuboidal inclusions 0.6 micron in diameter were composed of 100 A thick osmiophilic striations spaced to produce a 150 A periodicity. In Nostoc sp. (588) the elongate, 0.1 micron by 2.5 micron, crystalloids were composed of 100 A thick osmiophilic striations spaced to produce a 200 A periodicity. N. punctiforme (1629) and N. calciola (B382) contained intrathylakoidal crystalloids which consisted of short curved segments with 100 A thick osmiophilic striations producing a 200 A periodicity. Granular areas were observed in 2 isolates of Anabaena and 5 of Nostoc. These bodies found in various locations in the cells, were interpreted to be elongate structures 0.2 micron thick, 1.2 micron long and about 5 micron in depth. These inclusions were composed of 15 nm diameter granules which in some section planes appeared in rows spaced 20 nm apart. Spherical bodies up to 0.7 micron in diameter and of medium electron density were observed in 4 isolates of Anabaena and 2 of Nostoc. Convoluted inclusions were found in N. calcicola (B382) and Anabaena sp. (1551). These roughly spherical bodies up to 0.8 micron in diameter contain lighter swirled areas.", "contents": "Paracrystalline inclusions in various isolates of the blue-green bacteria Nostoc and Anabaena. A number of different crystalline inclusions were observed in various isolates of Anabaena and Nostoc. Membrane-limited crystalline bodies were observed in 7 of 20 isolates of Anabaena and 19 of 29 isolates of Nostoc. These are spherical, single membrane-limited bodies from 0.6 to 0.1 micron in diameter. In most of the isolates they contained needle-like crystals 20 A in thickness and up to 80 nm in length. In 9 of the isolates the inclusions contained granular and fibrillar material. The number of bodies per cell varied in the different isolates from only a few, observed in many sections, up to 5 in a single section of A. subtropica (B1618). Crystalloids were observed in the cytoplasm of Anabaena sp. (1551), N. calcicola (B382), Nostoc sp. (588), and N. punctiforme (1629). In Anabaena sp. (1551) the roughly cuboidal inclusions 0.6 micron in diameter were composed of 100 A thick osmiophilic striations spaced to produce a 150 A periodicity. In Nostoc sp. (588) the elongate, 0.1 micron by 2.5 micron, crystalloids were composed of 100 A thick osmiophilic striations spaced to produce a 200 A periodicity. N. punctiforme (1629) and N. calciola (B382) contained intrathylakoidal crystalloids which consisted of short curved segments with 100 A thick osmiophilic striations producing a 200 A periodicity. Granular areas were observed in 2 isolates of Anabaena and 5 of Nostoc. These bodies found in various locations in the cells, were interpreted to be elongate structures 0.2 micron thick, 1.2 micron long and about 5 micron in depth. These inclusions were composed of 15 nm diameter granules which in some section planes appeared in rows spaced 20 nm apart. Spherical bodies up to 0.7 micron in diameter and of medium electron density were observed in 4 isolates of Anabaena and 2 of Nostoc. Convoluted inclusions were found in N. calcicola (B382) and Anabaena sp. (1551). These roughly spherical bodies up to 0.8 micron in diameter contain lighter swirled areas."}
{"id": "PMID:223817", "title": "Small cell carcinoma of the lung. Prognosis in relation to histologic subtype.", "content": "Forty-six of 59 patients with small cell carcinoma of the lung who were treated with multiple drug chemotherapy and radiotherapy were subclassified according to the World Health Organization classification. Subtyping was not possible in the 13 other patients who were diagnosed on sputum cytology findings alone. There was no significant difference in extent of disease, response, duration of response to treatment, or median survival between the different subtypes. Two main difficulties arise in applying the subtyping classification. First, many tumors showed features of several histologic subtypes, implying the existence of a morphologic continuum within the general group of small cell anaplastic carcinomas. Second, tissue crushing artefact was common. Our results do not reveal any advantage in knowing the tumor subtype. It remains essential to differentiate small cell anaplastic carcinoma from other forms of lung carcinoma not responsive to chemotherapy.", "contents": "Small cell carcinoma of the lung. Prognosis in relation to histologic subtype. Forty-six of 59 patients with small cell carcinoma of the lung who were treated with multiple drug chemotherapy and radiotherapy were subclassified according to the World Health Organization classification. Subtyping was not possible in the 13 other patients who were diagnosed on sputum cytology findings alone. There was no significant difference in extent of disease, response, duration of response to treatment, or median survival between the different subtypes. Two main difficulties arise in applying the subtyping classification. First, many tumors showed features of several histologic subtypes, implying the existence of a morphologic continuum within the general group of small cell anaplastic carcinomas. Second, tissue crushing artefact was common. Our results do not reveal any advantage in knowing the tumor subtype. It remains essential to differentiate small cell anaplastic carcinoma from other forms of lung carcinoma not responsive to chemotherapy."}
{"id": "PMID:223818", "title": "Unilateral hyperlucent lung. Patent ductus arteriosus coexisting with bronchial carcinoid.", "content": "We report an unusual case of patent ductus arteriosus (PDA) co-existing with bronchial carcinoid. The initial radiographic presentation was hyperlucent lung. Causes and possible mechanisms of unilateral hypoperfusion of the lung are reviewed briefly. Useful diagnostic modalities in evaluating a hyperlucent lung are also discussed.", "contents": "Unilateral hyperlucent lung. Patent ductus arteriosus coexisting with bronchial carcinoid. We report an unusual case of patent ductus arteriosus (PDA) co-existing with bronchial carcinoid. The initial radiographic presentation was hyperlucent lung. Causes and possible mechanisms of unilateral hypoperfusion of the lung are reviewed briefly. Useful diagnostic modalities in evaluating a hyperlucent lung are also discussed."}
{"id": "PMID:223820", "title": "Laparoscopic diagnosis of suspected liver neoplasms. Value of prior liver scans.", "content": "To study the efficacy of standard blood tests of liver function (LFTs) and technetium-99m liver scan followed by laparoscopy in the diagnosis of solid malignant tumors of the liver, 100 consecutive patients were evaluated who had these tests because of clinical suspicion of liver neoplasm. Malignant liver tumors were present in 65 of the 100 patients. Laparoscopy diagnosed 60 of the 65, and the neoplasms were documented pathologically by directed biopsy (92% sensitivity, 100% specificity). In 8 patients, hepatoma was diagnosed and staged for possible resection. A negative \"blind\" biopsy had been performed in 23 of the 60 patients with liver neoplasms diagnosed at laparoscopy. LFTs and liver scans together were good screening tests (95% sensitivity) but had low specificity (46%). Liver scans also provided information as to probable tumor location in the liver, guiding the insertion site for the laparoscope, and directing deep-needle biopsies if no surface lesions were seen.", "contents": "Laparoscopic diagnosis of suspected liver neoplasms. Value of prior liver scans. To study the efficacy of standard blood tests of liver function (LFTs) and technetium-99m liver scan followed by laparoscopy in the diagnosis of solid malignant tumors of the liver, 100 consecutive patients were evaluated who had these tests because of clinical suspicion of liver neoplasm. Malignant liver tumors were present in 65 of the 100 patients. Laparoscopy diagnosed 60 of the 65, and the neoplasms were documented pathologically by directed biopsy (92% sensitivity, 100% specificity). In 8 patients, hepatoma was diagnosed and staged for possible resection. A negative \"blind\" biopsy had been performed in 23 of the 60 patients with liver neoplasms diagnosed at laparoscopy. LFTs and liver scans together were good screening tests (95% sensitivity) but had low specificity (46%). Liver scans also provided information as to probable tumor location in the liver, guiding the insertion site for the laparoscope, and directing deep-needle biopsies if no surface lesions were seen."}
{"id": "PMID:223821", "title": "Effects of pancreatic polypeptide and vasoactive intestinal polypeptide on rat ileal and colonic water and electrolyte transport in vivo.", "content": "Two gastrointestinal peptides, vasoactive intestinal polypeptide (VIP) and pancreatic polypeptide, suspected of being associated with symptoms of WDHA syndrome (pancreatic cholera) were tested on the rat small and large intestine for their effects on water and electrolyte transport. Intravenous infusion of VIP (14.3 microgram/kg/hr) inhibited net absorption of water and electrolytes in the ileum and reversed net absorption to net secretion in the colon. In contrast, bovine pancreatic polypeptide (52 microgram/kg/hr) did not inhibit absorption or stimulate secretion. These data indicate VIP causes colonic secretion in vivo, an effect previously shown only in vitro, and that bovine pancreatic polypeptide (at this dose) is not a secretagogue in the small or large intestine of the rat. Thus, while consistent with VIP being a contributory agent to the secretion of pancreatic cholera, the data do not support the notion that pancreatic polypeptide might be a causative agent in this syndrome.", "contents": "Effects of pancreatic polypeptide and vasoactive intestinal polypeptide on rat ileal and colonic water and electrolyte transport in vivo. Two gastrointestinal peptides, vasoactive intestinal polypeptide (VIP) and pancreatic polypeptide, suspected of being associated with symptoms of WDHA syndrome (pancreatic cholera) were tested on the rat small and large intestine for their effects on water and electrolyte transport. Intravenous infusion of VIP (14.3 microgram/kg/hr) inhibited net absorption of water and electrolytes in the ileum and reversed net absorption to net secretion in the colon. In contrast, bovine pancreatic polypeptide (52 microgram/kg/hr) did not inhibit absorption or stimulate secretion. These data indicate VIP causes colonic secretion in vivo, an effect previously shown only in vitro, and that bovine pancreatic polypeptide (at this dose) is not a secretagogue in the small or large intestine of the rat. Thus, while consistent with VIP being a contributory agent to the secretion of pancreatic cholera, the data do not support the notion that pancreatic polypeptide might be a causative agent in this syndrome."}
{"id": "PMID:223826", "title": "[ADAM complex--maxillofacial abnormalities and abnormalities of the extremities caused by amniotic strangulations].", "content": "The anomalies of the ADAM complex arise through amniotic strangulations, adhesions and amputations. In the face cleft formations, displacements and deformities of various structures occur. The limbs exhibit constriction grooves, secondary syndactyle or amptuations. According to observations on 8 patients and information from the literature, the presentation of Adam complexes can vary to an extraordinary degree. The anomalies result from exogenous influences. In genetic counselling phenotypically similar congenital malformations must be separated.", "contents": "[ADAM complex--maxillofacial abnormalities and abnormalities of the extremities caused by amniotic strangulations]. The anomalies of the ADAM complex arise through amniotic strangulations, adhesions and amputations. In the face cleft formations, displacements and deformities of various structures occur. The limbs exhibit constriction grooves, secondary syndactyle or amptuations. According to observations on 8 patients and information from the literature, the presentation of Adam complexes can vary to an extraordinary degree. The anomalies result from exogenous influences. In genetic counselling phenotypically similar congenital malformations must be separated."}
{"id": "PMID:223827", "title": "alpha-Melanocyte-stimulating hormone and adrenocorticotropin in the regulation of glucocorticoid secretion during the perinatal period in sheep.", "content": "To determine the role of other ACTH-like peptides in the regulation of glucocorticoid secretion in fetal sheep, we examined the responses of the adrenal gland of fetal and newborn sheep to comparable single doses of alpha MSH (75 micrograms) or ACTH (50 micrograms) during the last third of gestation and the first month of postnatal life. alpha MSH first increased the plasma glucocorticoid concentration at 121--130 days of gestation [from 16 +/- 1.5 to 36.9 +/- 9 (SE) ng/ml]; the response to alpha MSH persisted on days 131--140 of gestation and during the first month after birth. ACTH first increased the plasma glucocorticoid concentration at 131--140 days of gestation and increased it further in the first month after birth (from 18.9 +/- 3.6 to 97.0 +/- 10 ng/ml). The observations that the adrenal glands of fetuses and newborn lambs responded to alpha MSH at a dose comparable to that of ACTH and that the response to alpha MSH in the fetus preceded the response to ACTH may indicate that adrenal receptors mature during fetal development. These data also suggest that the regulation of the adrenal during fetal life may involve more than one tropic hormone.", "contents": "alpha-Melanocyte-stimulating hormone and adrenocorticotropin in the regulation of glucocorticoid secretion during the perinatal period in sheep. To determine the role of other ACTH-like peptides in the regulation of glucocorticoid secretion in fetal sheep, we examined the responses of the adrenal gland of fetal and newborn sheep to comparable single doses of alpha MSH (75 micrograms) or ACTH (50 micrograms) during the last third of gestation and the first month of postnatal life. alpha MSH first increased the plasma glucocorticoid concentration at 121--130 days of gestation [from 16 +/- 1.5 to 36.9 +/- 9 (SE) ng/ml]; the response to alpha MSH persisted on days 131--140 of gestation and during the first month after birth. ACTH first increased the plasma glucocorticoid concentration at 131--140 days of gestation and increased it further in the first month after birth (from 18.9 +/- 3.6 to 97.0 +/- 10 ng/ml). The observations that the adrenal glands of fetuses and newborn lambs responded to alpha MSH at a dose comparable to that of ACTH and that the response to alpha MSH in the fetus preceded the response to ACTH may indicate that adrenal receptors mature during fetal development. These data also suggest that the regulation of the adrenal during fetal life may involve more than one tropic hormone."}
{"id": "PMID:223830", "title": "Nitrogenous compounds reversibly inhibit the adenosine 3',5'-monophosphate response to thyrotropin: this effect is dissociated from altered guanine 3',5'-monophosphate levels.", "content": "Nitrogenous compounds were studied for their effect on cGMP levels in the thyroid. Several agents, including sodium nitrite and hydroxylamine, could generate a rise of over 100-fold in cGMP. At a concentration of 20 mM, HN2OH and NaNO2 significantly reduced cAMP levels previously generated by 0.5 mU/ml TSH. If the slices were rinsed and placed in new buffer without the latter nitrogenous compound, the cAMP response to TSH was restored even though intracellular cGMP levels remained elevated. Thus, the counterregulatory effect of these agents on cAMP levels is not correlated with the presence of high levels of cGMP per se. Both the rise in cGMP and the fall in cAMP could still be detected when Ca++ was deleted from the incubation medium, in contrast to other reported stimuli that elevate cGMP levels in the thyroid.", "contents": "Nitrogenous compounds reversibly inhibit the adenosine 3',5'-monophosphate response to thyrotropin: this effect is dissociated from altered guanine 3',5'-monophosphate levels. Nitrogenous compounds were studied for their effect on cGMP levels in the thyroid. Several agents, including sodium nitrite and hydroxylamine, could generate a rise of over 100-fold in cGMP. At a concentration of 20 mM, HN2OH and NaNO2 significantly reduced cAMP levels previously generated by 0.5 mU/ml TSH. If the slices were rinsed and placed in new buffer without the latter nitrogenous compound, the cAMP response to TSH was restored even though intracellular cGMP levels remained elevated. Thus, the counterregulatory effect of these agents on cAMP levels is not correlated with the presence of high levels of cGMP per se. Both the rise in cGMP and the fall in cAMP could still be detected when Ca++ was deleted from the incubation medium, in contrast to other reported stimuli that elevate cGMP levels in the thyroid."}
{"id": "PMID:223832", "title": "Effect of stress, adrenocorticotropin or corticosteroid treatment, adrenalectomy, or hypophysectomy on hypothalamic immunoreactive adrenocorticotropin concentrations.", "content": "Despite variations in plasma and/or pituitary ACTH concentrations, no changes in median eminence or medial basal hypothalamic immunoreactive ACTH-like concentrations were seen in rats studied 6 weeks posthypophysectomy, 12 h or 28 days after bilateral adrenalectomy, 6 days after implantation of corticosterone pellets (75 mg), after dexamethasone administration (300 micrograms/100 g BW, ip, twice daily for 4 days), or after chronic immobilization stress. The lack of concordant variation of brain, pituitary, and plasma ACTH concentrations further supports the suggestion of a nonpituitary, central nervous system origin of some portion of brain immunoreactive ACTH-like activity.", "contents": "Effect of stress, adrenocorticotropin or corticosteroid treatment, adrenalectomy, or hypophysectomy on hypothalamic immunoreactive adrenocorticotropin concentrations. Despite variations in plasma and/or pituitary ACTH concentrations, no changes in median eminence or medial basal hypothalamic immunoreactive ACTH-like concentrations were seen in rats studied 6 weeks posthypophysectomy, 12 h or 28 days after bilateral adrenalectomy, 6 days after implantation of corticosterone pellets (75 mg), after dexamethasone administration (300 micrograms/100 g BW, ip, twice daily for 4 days), or after chronic immobilization stress. The lack of concordant variation of brain, pituitary, and plasma ACTH concentrations further supports the suggestion of a nonpituitary, central nervous system origin of some portion of brain immunoreactive ACTH-like activity."}
{"id": "PMID:223837", "title": "Gonadotropin binding and testicular function in old rats.", "content": "Serum testosterone levels, testicular LH binding and the spermatogenic cycle were analyzed in rats 4 and 22 mo of age. With age, serum testosterone levels decreased from 3.2 to 0.63 ng/ml serum. There was no age related decline in testicular LH binding or changes in the spermatogenic cycle.", "contents": "Gonadotropin binding and testicular function in old rats. Serum testosterone levels, testicular LH binding and the spermatogenic cycle were analyzed in rats 4 and 22 mo of age. With age, serum testosterone levels decreased from 3.2 to 0.63 ng/ml serum. There was no age related decline in testicular LH binding or changes in the spermatogenic cycle."}
{"id": "PMID:223838", "title": "Biphasic inhibitory and stimulatory effects of thyrotropin on the mitotic activity of thyroid explants cultured in vitro.", "content": "An influence of thyrotropin (TSH), dibutyryl cyclic AMP (dbcAMP), triiodothyronine (T3) and thyroxine (T4) on the mitotic incidence in the organ-cultured rat thyroid was studied. The study has revealed biphasic inhibitory and stimulatory effects of TSH on the thyroid mitotic activity. The inhibitory effect occurred 14 h after an exposure of the thyroid explants to TSH and was enhanced by T3. A similar inhibitory effect was observed after an exposure of the explants to dbcAMP. 24 h after the exposure of the thyroid explants to TSH a stimulatory effect on the mitotic incidence was observed. The latter effect was not reproduced by dbcAMP.", "contents": "Biphasic inhibitory and stimulatory effects of thyrotropin on the mitotic activity of thyroid explants cultured in vitro. An influence of thyrotropin (TSH), dibutyryl cyclic AMP (dbcAMP), triiodothyronine (T3) and thyroxine (T4) on the mitotic incidence in the organ-cultured rat thyroid was studied. The study has revealed biphasic inhibitory and stimulatory effects of TSH on the thyroid mitotic activity. The inhibitory effect occurred 14 h after an exposure of the thyroid explants to TSH and was enhanced by T3. A similar inhibitory effect was observed after an exposure of the explants to dbcAMP. 24 h after the exposure of the thyroid explants to TSH a stimulatory effect on the mitotic incidence was observed. The latter effect was not reproduced by dbcAMP."}
{"id": "PMID:223840", "title": "Purification and properties of sheep-liver aldehyde dehydrogenases.", "content": "Sheep liver cytoplasmic aldehyde dehydrogenase was purified to homogeneity to give a sample with a specific activity of 380 nmol NADH min(-1) mg(-1). An amino acid analysis of the enzyme gave results similar to those reported for aldehyde dehydrogenases from other sources. The isoelectric point was at pH 5.25 and the enzyme contained no significant amounts of metal ions. On the binding of NADH to the enzyme there is a shift in absorption maximum of NADH to 344 nm, and a 5.6-fold enhancement of nucleotide fluorescence. The protein fluorescence (lambdaexcit = 290 nm, lambdaemisson = 340 nm) is quenched on the binding of NAD+ and NADH. The enhancement of nucleotide fluorescence on the binding of NADH has been utilised to determine the dissociation constant for the enzyme . NADH complex (Kd = 1.2 +/- 0.2 muM). A Hill plot of the data gave a straight line with a slope of 1.0 +/- 0.3 indicating the absence of co-operative effects. Ellman's reagent reacted only slowly with the enzyme but in the presence of sodium dodecylsulphate complete reaction occurred within a few minutes to an extent corresponding to 36 thiol groups/enzyme. Molecular weights were determined for both cytoplasmic and mitochondrial aldehyde dehydrogenases and were 212 000 +/- 8 000 and 205 000 respectively. Each enzyme consisted of four subunits with molecular weight of 53 000 +/- 2 000. Properties of the cytoplasmic and mitochondrial aldehyde dehydrogenases from sheep liver were compared with other mammalian liver aldehyde dehydrogenases.", "contents": "Purification and properties of sheep-liver aldehyde dehydrogenases. Sheep liver cytoplasmic aldehyde dehydrogenase was purified to homogeneity to give a sample with a specific activity of 380 nmol NADH min(-1) mg(-1). An amino acid analysis of the enzyme gave results similar to those reported for aldehyde dehydrogenases from other sources. The isoelectric point was at pH 5.25 and the enzyme contained no significant amounts of metal ions. On the binding of NADH to the enzyme there is a shift in absorption maximum of NADH to 344 nm, and a 5.6-fold enhancement of nucleotide fluorescence. The protein fluorescence (lambdaexcit = 290 nm, lambdaemisson = 340 nm) is quenched on the binding of NAD+ and NADH. The enhancement of nucleotide fluorescence on the binding of NADH has been utilised to determine the dissociation constant for the enzyme . NADH complex (Kd = 1.2 +/- 0.2 muM). A Hill plot of the data gave a straight line with a slope of 1.0 +/- 0.3 indicating the absence of co-operative effects. Ellman's reagent reacted only slowly with the enzyme but in the presence of sodium dodecylsulphate complete reaction occurred within a few minutes to an extent corresponding to 36 thiol groups/enzyme. Molecular weights were determined for both cytoplasmic and mitochondrial aldehyde dehydrogenases and were 212 000 +/- 8 000 and 205 000 respectively. Each enzyme consisted of four subunits with molecular weight of 53 000 +/- 2 000. Properties of the cytoplasmic and mitochondrial aldehyde dehydrogenases from sheep liver were compared with other mammalian liver aldehyde dehydrogenases."}
{"id": "PMID:223841", "title": "Some comments on the article: 'The Structure of Human-Plasma Low-Density Lipoprotein B. An X-Ray Small-Angle Scattering Study' by K. Muller, P. Laggner, O. Glatter, and G. Kostner [Eur. J. Biochem. 82, 73--90 (1978)].", "content": "In their paper, K. Muller, P. Laggner, O. Glatter and G. Kostner report X-ray scattering and density experiments on human plasma low-density lipoprotein B, performed at different solvent densities (i.e. contrast variation method). The interpretation of the experimental data lead those authors to question the use of that method and particularly the use of the characteristic scattering functions in the study of serum lipoproteins. In the present paper it is shown that several aspects of their analysis are in fact highly questionable and that the objections raised are therefore unfounded.", "contents": "Some comments on the article: 'The Structure of Human-Plasma Low-Density Lipoprotein B. An X-Ray Small-Angle Scattering Study' by K. Muller, P. Laggner, O. Glatter, and G. Kostner [Eur. J. Biochem. 82, 73--90 (1978)]. In their paper, K. Muller, P. Laggner, O. Glatter and G. Kostner report X-ray scattering and density experiments on human plasma low-density lipoprotein B, performed at different solvent densities (i.e. contrast variation method). The interpretation of the experimental data lead those authors to question the use of that method and particularly the use of the characteristic scattering functions in the study of serum lipoproteins. In the present paper it is shown that several aspects of their analysis are in fact highly questionable and that the objections raised are therefore unfounded."}
{"id": "PMID:223843", "title": "Evidence for ligand-induced conformational changes in rabbit-muscle glyceraldehyde-3-phosphate dehydrogenase.", "content": "The tetrameric glyceraldehyde-3-phosphate dehydrogenase from rabbit muscle binds NAD+ and some of its analogues in a negatively cooperative manner, whereas other NAD+ analogues bind non-cooperatively to this enzyme. Subsequent to alkylation of a fraction of the active sites of the enzyme with the fluorescent SH reagent N-iodoacetyl-N'-(5-sulfo-1-naphthyl)-ethylenediamine, it was found that the alkylated sites bind NAD+ and NAD+ analogues with a markedly reduced affinity as compared with non-alkylated sites. It was therefore feasible to measure the fluorescence and the circular polarization of the luminescence of the enzyme-bound alkyl groups as a function of binding of NAD+ and of NAD+ analogues to the non-alkylated sites. The changes observed indicate that ligand binding to the non-alkylated sites induces changes in the fluorescence properties of the alkyl groups bound to neighbouring subunits, most likely through the protein moiety. The nature of these changes appears to depend on the structure of the coenzyme analogue. The binding of the non-cooperative binders acetyl-pyridine--adenine dinucleotide, ATP and ADP-ribose induce different conformational changes in the neighbouring vacant subunit, as monitored by the spectroscopic properties of the bound alkyl group. These results in conjunction with other data support the view that the negative cooperativity in NAD+ binding to glyceraldehyde-3-phosphate dehydrogenase results from ligand-induced conformational changes. Furthermore, these results further support the view that subtle structural changes in the coenzyme molecule determine the nature of the conformational changes induced within the enzyme tetramer.", "contents": "Evidence for ligand-induced conformational changes in rabbit-muscle glyceraldehyde-3-phosphate dehydrogenase. The tetrameric glyceraldehyde-3-phosphate dehydrogenase from rabbit muscle binds NAD+ and some of its analogues in a negatively cooperative manner, whereas other NAD+ analogues bind non-cooperatively to this enzyme. Subsequent to alkylation of a fraction of the active sites of the enzyme with the fluorescent SH reagent N-iodoacetyl-N'-(5-sulfo-1-naphthyl)-ethylenediamine, it was found that the alkylated sites bind NAD+ and NAD+ analogues with a markedly reduced affinity as compared with non-alkylated sites. It was therefore feasible to measure the fluorescence and the circular polarization of the luminescence of the enzyme-bound alkyl groups as a function of binding of NAD+ and of NAD+ analogues to the non-alkylated sites. The changes observed indicate that ligand binding to the non-alkylated sites induces changes in the fluorescence properties of the alkyl groups bound to neighbouring subunits, most likely through the protein moiety. The nature of these changes appears to depend on the structure of the coenzyme analogue. The binding of the non-cooperative binders acetyl-pyridine--adenine dinucleotide, ATP and ADP-ribose induce different conformational changes in the neighbouring vacant subunit, as monitored by the spectroscopic properties of the bound alkyl group. These results in conjunction with other data support the view that the negative cooperativity in NAD+ binding to glyceraldehyde-3-phosphate dehydrogenase results from ligand-induced conformational changes. Furthermore, these results further support the view that subtle structural changes in the coenzyme molecule determine the nature of the conformational changes induced within the enzyme tetramer."}
{"id": "PMID:223844", "title": "Aggregation of sponge cells. Isolation and characterization of an inhibitor of aggregation receptor from the cell surface.", "content": "From the cell membranes of the sponge Geodia cydonium a component was isolated and purified which inhibits the aggregation factor isolated from the same source; the component was termed anti-aggregation receptor. This molecule was characterized as a glycoprotein (54% neutral carbohydrate) and its molecular weight is in the range of 180,000 One biological site of the anti-aggregation receptor was determined to be D-galactose. Indirect evidence presented seems to indicate that this molecule is present in an active form in aggregation-deficient cells and absent in aggregation-susceptible cells.", "contents": "Aggregation of sponge cells. Isolation and characterization of an inhibitor of aggregation receptor from the cell surface. From the cell membranes of the sponge Geodia cydonium a component was isolated and purified which inhibits the aggregation factor isolated from the same source; the component was termed anti-aggregation receptor. This molecule was characterized as a glycoprotein (54% neutral carbohydrate) and its molecular weight is in the range of 180,000 One biological site of the anti-aggregation receptor was determined to be D-galactose. Indirect evidence presented seems to indicate that this molecule is present in an active form in aggregation-deficient cells and absent in aggregation-susceptible cells."}
{"id": "PMID:223845", "title": "Studies on the methylation of cytoplasmic ribosomal RNA from cultured higher plant cells.", "content": "The methylation of cytoplasmic ribosomal RNA of cultured sycamore cells (Acer pseudoplatanus L.) was investigated. Labelled 17-S and 26-S rRNA were prepared from cells that had been incubated with either [32P]phosphate, [Me-3H]methionine or [Me-14C]methionine. Ion-exchange resin chromatography of 0.3 M KOH or 1 M HCl hydrolysates and two-dimensional chromatographic analyses of phosphodiesterase plus phosphatase digests of 17-S and 26-S rRNA were performed. 17-S and 26-S rRNA contain 49 and 91 methyl groups per molecule, respectively. These values were verified in sevemral ways. The high degree of methylation of sycamore rRNA, particularly for the 26-S rRNA, contrasts with the situation in all other investigated organisms. Several methylated bases were identified. 7-Methylguanine and 5-methylcytosine both occur in 17-S and 26-S rRNA. N6-Methyladenine and N6,N6-dimethyladenine are restricted to the 17-S rRNA while 3-methyluracil and 1-methyladenine occur in the 26-S rRNA. One hypermodified uridine was also tentatively identified in the small rRNA. In 17-S rRNA, there is one copy of 7-methylguanine, N6-methyladenine and hypermodified uridine and two copies of N6,N6-dimethyladenine. 3-Methyluracil, 1-methyladenine and 5-methylcytosine occur twice, twice and three times, respectively, in 26-S rRNA. 7-Methylguanine and 5-methylcytosine are only in submolar amounts in the 26-S and 17-S rRNA, respectively. There are 40 +/- 2 and 83 +/- 3 2'-O-methylriboses per 17-S and 26-S rRNA molecule, respectively. In addition to the four 2'-O-methylnucleosides, one 2'-O-methylpseudouridine is present in the 17-S rRNA. Several lines of evidence argues for a non-random distribution of the methylriboses. In particular, one and seven Nm-Nm-Np structures occur in the 17-S and 26-S rRNA, respectively. The data are discussed comparatively with the methylation pattern of Escherichia coli, yeast and HeLa cell rRNA.", "contents": "Studies on the methylation of cytoplasmic ribosomal RNA from cultured higher plant cells. The methylation of cytoplasmic ribosomal RNA of cultured sycamore cells (Acer pseudoplatanus L.) was investigated. Labelled 17-S and 26-S rRNA were prepared from cells that had been incubated with either [32P]phosphate, [Me-3H]methionine or [Me-14C]methionine. Ion-exchange resin chromatography of 0.3 M KOH or 1 M HCl hydrolysates and two-dimensional chromatographic analyses of phosphodiesterase plus phosphatase digests of 17-S and 26-S rRNA were performed. 17-S and 26-S rRNA contain 49 and 91 methyl groups per molecule, respectively. These values were verified in sevemral ways. The high degree of methylation of sycamore rRNA, particularly for the 26-S rRNA, contrasts with the situation in all other investigated organisms. Several methylated bases were identified. 7-Methylguanine and 5-methylcytosine both occur in 17-S and 26-S rRNA. N6-Methyladenine and N6,N6-dimethyladenine are restricted to the 17-S rRNA while 3-methyluracil and 1-methyladenine occur in the 26-S rRNA. One hypermodified uridine was also tentatively identified in the small rRNA. In 17-S rRNA, there is one copy of 7-methylguanine, N6-methyladenine and hypermodified uridine and two copies of N6,N6-dimethyladenine. 3-Methyluracil, 1-methyladenine and 5-methylcytosine occur twice, twice and three times, respectively, in 26-S rRNA. 7-Methylguanine and 5-methylcytosine are only in submolar amounts in the 26-S and 17-S rRNA, respectively. There are 40 +/- 2 and 83 +/- 3 2'-O-methylriboses per 17-S and 26-S rRNA molecule, respectively. In addition to the four 2'-O-methylnucleosides, one 2'-O-methylpseudouridine is present in the 17-S rRNA. Several lines of evidence argues for a non-random distribution of the methylriboses. In particular, one and seven Nm-Nm-Np structures occur in the 17-S and 26-S rRNA, respectively. The data are discussed comparatively with the methylation pattern of Escherichia coli, yeast and HeLa cell rRNA."}
{"id": "PMID:223846", "title": "Properties of herpes simplex virus DNA polymerase and characterization of its associated exonuclease activity.", "content": "Herpes simplex virus (HSV) DNA polymerase was isolated on a large-scale from African green monkey kidney cells infected with HSV type 1 (HSV-1) strain Angelotti. After DNA-cellulose chromatography the enzyme showed a specific activity of 48,000 units/mg protein. Three major single polypeptides with molecular weights of 144,000, 74,000 and 29,000 were copurified with the enzyme activity at the DNA-cellulose ste. By its chromatographic behavior and by template studies, the HSV DNA polymerase activity was clearly distinguishable from cellular alpha, beta and gamma DNA polymerase activities. Two exonucleolytic activities were found in the DNA-cellulose enzyme preparation. The main exonucleolytic activity, which degraded both single-stranded and double-stranded DNA to deoxynucleoside 5'-monophosphates, was separated by subsequent velocity sedimentation. The remaining exonucleolytic activity was not separable from the HSV DNA polymerase by several chromatographic steps and by velocity sedimentation at high ionic strength. This novel exonuclease and HSV DNA polymerase were equally sensitive both to phosphonoacetic acid and Zn2+ ions, inhibitors of the viral polymerase. Similar to the 3'-to-5'-exonuclease of procaryotic DNA polymerases and mammalian DNA polymerase delta, the HSV-polymerase-associated exonuclease catalyzed the removal of 3'-terminal nucleotides from the primer/template as well as the template-dependent conversion of deoxynucleoside triphosphates to monophosphates.", "contents": "Properties of herpes simplex virus DNA polymerase and characterization of its associated exonuclease activity. Herpes simplex virus (HSV) DNA polymerase was isolated on a large-scale from African green monkey kidney cells infected with HSV type 1 (HSV-1) strain Angelotti. After DNA-cellulose chromatography the enzyme showed a specific activity of 48,000 units/mg protein. Three major single polypeptides with molecular weights of 144,000, 74,000 and 29,000 were copurified with the enzyme activity at the DNA-cellulose ste. By its chromatographic behavior and by template studies, the HSV DNA polymerase activity was clearly distinguishable from cellular alpha, beta and gamma DNA polymerase activities. Two exonucleolytic activities were found in the DNA-cellulose enzyme preparation. The main exonucleolytic activity, which degraded both single-stranded and double-stranded DNA to deoxynucleoside 5'-monophosphates, was separated by subsequent velocity sedimentation. The remaining exonucleolytic activity was not separable from the HSV DNA polymerase by several chromatographic steps and by velocity sedimentation at high ionic strength. This novel exonuclease and HSV DNA polymerase were equally sensitive both to phosphonoacetic acid and Zn2+ ions, inhibitors of the viral polymerase. Similar to the 3'-to-5'-exonuclease of procaryotic DNA polymerases and mammalian DNA polymerase delta, the HSV-polymerase-associated exonuclease catalyzed the removal of 3'-terminal nucleotides from the primer/template as well as the template-dependent conversion of deoxynucleoside triphosphates to monophosphates."}
{"id": "PMID:223848", "title": "Cytochrome c oxidase subunits in nuclear and extranuclear cytochrome-aa3-deficient mutants of Neurospora crassa.", "content": "The mitochondria of cytochrome-aa3-deficient Neurospora crassa mutants were screened for the seven polypeptide constiuents of cytochrome c oxidase. The polypeptides of the holoenzyme and the unassembled or partially assembled subunits were detected by sodium dodecyl sulfate/acrylamide gel electrophoresis of immunoprecipitates obtained with antiserum to the holoenzyme as well as to several individual subunits. With respect to the mitochondrially synthesized polypeptides of the oxidase, subunits 1 to 3, the results obtained from the analysis of immunoprecipitates were confirmed through the direct electrophoretic analysis of mitochondrial translation products. The results were as follows. 1. The mitochondria of the cya-2-8 and cya-3-16 nuclear mutants and the [exn-5] cytoplasmic mutant contained a protein complex immunoprecipitated by anti-holoenzyme antibody and composed of the complete set of the seven cytochrome oxidase polypeptides. Only the oxidase subunits 5 and 6 were immunoprecipitated by anti-holoenzyme antibody from the mitochondria of the cyt-2-1 and 299-1 nuclear mutants, even though at least some of the mitochondrially synthesized polypeptides were detected in both mutants by subunit specific immunoprecipitation. 2. A 'subunit 1' polypeptide larger than the authentic subunit-1 polypeptide of wild-type cytochrome oxidase was found in the mitochondria from two nuclear mutants, cyt-2-1, and 299-1 and the [mi-3] cytoplasmic mutant. This larger polypeptide may be an unprocessed precursor of the 'mature' subunit 1 protein of the holoenzyme. No changes in the apparent molecular weights were found for the polypeptide subunits of cytochrome oxidase in mitochondria of the [exn-5] cytoplasmic mutant and the cya-2-8 and cya-4-23 nuclear mutants. 3. A nuclear mutant, 299-1, lacks the mitochondrially synthesized subunit-2 polypeptide of cytochrome oxidase. When cells were labelled in the presence of cycloheximide, the subunit 2 content of mitochondria from mutants [exn-5], cya-2-8, cya-3-16 and cya-4-23 was lower than in mitochondria from wild-type. This deficiency, however, does not appear to be sufficiently severe to fully account for the lack of cytochrome aa3 in these mutants. The cya-4-23 nuclear mutant either is severely deficient in or lacks cytochrome oxidase subunits 5 and 6. On the basis of these and previously reported observations, it is proposed that the cytochrome oxidase deficiencies of as many as seven of the eight N. crassa cytochrome-aa3-deficient mutants could be caused by genetically imposed alterations in regulatory systems controlling the production of different components of the enzyme.", "contents": "Cytochrome c oxidase subunits in nuclear and extranuclear cytochrome-aa3-deficient mutants of Neurospora crassa. The mitochondria of cytochrome-aa3-deficient Neurospora crassa mutants were screened for the seven polypeptide constiuents of cytochrome c oxidase. The polypeptides of the holoenzyme and the unassembled or partially assembled subunits were detected by sodium dodecyl sulfate/acrylamide gel electrophoresis of immunoprecipitates obtained with antiserum to the holoenzyme as well as to several individual subunits. With respect to the mitochondrially synthesized polypeptides of the oxidase, subunits 1 to 3, the results obtained from the analysis of immunoprecipitates were confirmed through the direct electrophoretic analysis of mitochondrial translation products. The results were as follows. 1. The mitochondria of the cya-2-8 and cya-3-16 nuclear mutants and the [exn-5] cytoplasmic mutant contained a protein complex immunoprecipitated by anti-holoenzyme antibody and composed of the complete set of the seven cytochrome oxidase polypeptides. Only the oxidase subunits 5 and 6 were immunoprecipitated by anti-holoenzyme antibody from the mitochondria of the cyt-2-1 and 299-1 nuclear mutants, even though at least some of the mitochondrially synthesized polypeptides were detected in both mutants by subunit specific immunoprecipitation. 2. A 'subunit 1' polypeptide larger than the authentic subunit-1 polypeptide of wild-type cytochrome oxidase was found in the mitochondria from two nuclear mutants, cyt-2-1, and 299-1 and the [mi-3] cytoplasmic mutant. This larger polypeptide may be an unprocessed precursor of the 'mature' subunit 1 protein of the holoenzyme. No changes in the apparent molecular weights were found for the polypeptide subunits of cytochrome oxidase in mitochondria of the [exn-5] cytoplasmic mutant and the cya-2-8 and cya-4-23 nuclear mutants. 3. A nuclear mutant, 299-1, lacks the mitochondrially synthesized subunit-2 polypeptide of cytochrome oxidase. When cells were labelled in the presence of cycloheximide, the subunit 2 content of mitochondria from mutants [exn-5], cya-2-8, cya-3-16 and cya-4-23 was lower than in mitochondria from wild-type. This deficiency, however, does not appear to be sufficiently severe to fully account for the lack of cytochrome aa3 in these mutants. The cya-4-23 nuclear mutant either is severely deficient in or lacks cytochrome oxidase subunits 5 and 6. On the basis of these and previously reported observations, it is proposed that the cytochrome oxidase deficiencies of as many as seven of the eight N. crassa cytochrome-aa3-deficient mutants could be caused by genetically imposed alterations in regulatory systems controlling the production of different components of the enzyme."}
{"id": "PMID:223849", "title": "Regulation of protein synthesis.", "content": "A system of translational control in eukaryotes consists of (a) a proinhibitor and (b) an inhibitor of polypeptide chain initiation. The inhibitor (active eIF-2 kinase), a cAMP-independent protein kinase, catalyzes the phosphorylation by ATP of the small subunit of the polypeptide chain initiation factor eIF-2. This blocks the interaction of eIF-2 with eIF-2 stimulating protein (ESP) without which eIF-2 is unable to form an initiation complex, a prerequisite for translation. Our observations are consistent with the view that the proinhibitor (inactive eIF-2 kinase) is converted to the inhibitor by phosphorylation catalyzed by a cAMP-dependent protein kinase. This is analogous to the conversion of inactive phosphorylase kinase to active phosphorylase kinase. As in the case of phosphorylase kinase and phosphorylase, the modification of activity produced by phosphorylation of eIF-2 kinase and eIF-2 itself is probably reversed by dephosphorylation catalyzed by specific protein phosphatases (see diagram in Fig. 12) but no evidence bearing on this aspect of the problem is yet available. Hemin inhibits the cAMP-induced dissociation of the regulatory and catalytic subunits of cAMP-dependent protein kinase by binding to the regulatory subunit of the enzyme and blocking, through an allosteric effect, the binding of cAMP. Thus, hemin prevents the activation of eIF-2 kinase by inhibiting the cAMP-dependent protein kinase.", "contents": "Regulation of protein synthesis. A system of translational control in eukaryotes consists of (a) a proinhibitor and (b) an inhibitor of polypeptide chain initiation. The inhibitor (active eIF-2 kinase), a cAMP-independent protein kinase, catalyzes the phosphorylation by ATP of the small subunit of the polypeptide chain initiation factor eIF-2. This blocks the interaction of eIF-2 with eIF-2 stimulating protein (ESP) without which eIF-2 is unable to form an initiation complex, a prerequisite for translation. Our observations are consistent with the view that the proinhibitor (inactive eIF-2 kinase) is converted to the inhibitor by phosphorylation catalyzed by a cAMP-dependent protein kinase. This is analogous to the conversion of inactive phosphorylase kinase to active phosphorylase kinase. As in the case of phosphorylase kinase and phosphorylase, the modification of activity produced by phosphorylation of eIF-2 kinase and eIF-2 itself is probably reversed by dephosphorylation catalyzed by specific protein phosphatases (see diagram in Fig. 12) but no evidence bearing on this aspect of the problem is yet available. Hemin inhibits the cAMP-induced dissociation of the regulatory and catalytic subunits of cAMP-dependent protein kinase by binding to the regulatory subunit of the enzyme and blocking, through an allosteric effect, the binding of cAMP. Thus, hemin prevents the activation of eIF-2 kinase by inhibiting the cAMP-dependent protein kinase."}
{"id": "PMID:223852", "title": "The effect of prednisolone on neuromuscular transmission in the rat diaphragm.", "content": "Prednisolone, in concentrations of 0.004--0.032 mmol/l, increased the amplitude of the miniature end-plate potentials (MEPPs). A maximum increase to 134% of the control values was seen at 0.016 mmol/l. At higher prednisolone concentrations the MEPP amplitude gradually decreased to reach 77% of the control value at 0.62 mmol/l. The MEPP frequency was increased to twice the control value at 0.62 mmol/l. The quantal content of the end-plate potential (EPP), however, was not influenced by prednisolone. The response to iontophoretically applied acetylcholine was diminished, especially at 0.62 mmol/l prednisolone. Prednisolone, therefore, caused presynaptic effects as was shown by an increase in unitary MEPP amplitude and by a considerable number of giant MEPPs, which at increasing prednisolone concentrations was antagonized increasingly by a postsynaptic depressant effect. These results also provide an explanation for the adverse effects of prednisolone on the end-plate potential and on neuromuscular transmission.", "contents": "The effect of prednisolone on neuromuscular transmission in the rat diaphragm. Prednisolone, in concentrations of 0.004--0.032 mmol/l, increased the amplitude of the miniature end-plate potentials (MEPPs). A maximum increase to 134% of the control values was seen at 0.016 mmol/l. At higher prednisolone concentrations the MEPP amplitude gradually decreased to reach 77% of the control value at 0.62 mmol/l. The MEPP frequency was increased to twice the control value at 0.62 mmol/l. The quantal content of the end-plate potential (EPP), however, was not influenced by prednisolone. The response to iontophoretically applied acetylcholine was diminished, especially at 0.62 mmol/l prednisolone. Prednisolone, therefore, caused presynaptic effects as was shown by an increase in unitary MEPP amplitude and by a considerable number of giant MEPPs, which at increasing prednisolone concentrations was antagonized increasingly by a postsynaptic depressant effect. These results also provide an explanation for the adverse effects of prednisolone on the end-plate potential and on neuromuscular transmission."}
{"id": "PMID:223853", "title": "Opiate antagonist--receptor interaction unchanged by acute or chronic opiate treatment.", "content": "The apparent pA2 of naloxone, a measure of the apparent receptor affinity for the antagonist, was estimated in naive rats, in rats after acute and various schedules of chronic morphine pretreatment, and in rats during abrupt withdrawal. The results were adjusted to compensate for the amount of pretreatment drug in the rat brains as, otherwise, such a drug could have inflated the apparent pA2 values (see appendix). After this adjustment, a tendency of the apparent pA2 values to be increased after chronic pretreatment disappeared. The apparent pA2 of naloxone in acutely pretreated rats was also unchanged from that in naive rats, while the results in abruptly withdrawn rats were ambiguous. Thus, no change in the affinity of the antagonist for opiate receptors was found and theories suggesting that a conformational change takes place in the opiate receptor during the development of tolerance/dependence could not be supported.", "contents": "Opiate antagonist--receptor interaction unchanged by acute or chronic opiate treatment. The apparent pA2 of naloxone, a measure of the apparent receptor affinity for the antagonist, was estimated in naive rats, in rats after acute and various schedules of chronic morphine pretreatment, and in rats during abrupt withdrawal. The results were adjusted to compensate for the amount of pretreatment drug in the rat brains as, otherwise, such a drug could have inflated the apparent pA2 values (see appendix). After this adjustment, a tendency of the apparent pA2 values to be increased after chronic pretreatment disappeared. The apparent pA2 of naloxone in acutely pretreated rats was also unchanged from that in naive rats, while the results in abruptly withdrawn rats were ambiguous. Thus, no change in the affinity of the antagonist for opiate receptors was found and theories suggesting that a conformational change takes place in the opiate receptor during the development of tolerance/dependence could not be supported."}
{"id": "PMID:223854", "title": "Effects of external calcium ions and strontium ions on interactions of isoprenaline and its competitive inhibitor with beta-adrenoceptors in the intestinal smooth muscle.", "content": "The effects were tested of Ca ions and Sr ions on interactions of isoprenaline and its competitive inhibitor with beta-adrenoceptors in the taenia caecum from the guinea pig. Ca ions were involved in the combination of isoprenaline with the beta-adrenoceptors but not involved in the combination of the competitive inhibitor with the beta-adrenoceptors. Sr ions could not substitute for Ca ions in the isoprenaline--receptor interaction.", "contents": "Effects of external calcium ions and strontium ions on interactions of isoprenaline and its competitive inhibitor with beta-adrenoceptors in the intestinal smooth muscle. The effects were tested of Ca ions and Sr ions on interactions of isoprenaline and its competitive inhibitor with beta-adrenoceptors in the taenia caecum from the guinea pig. Ca ions were involved in the combination of isoprenaline with the beta-adrenoceptors but not involved in the combination of the competitive inhibitor with the beta-adrenoceptors. Sr ions could not substitute for Ca ions in the isoprenaline--receptor interaction."}
{"id": "PMID:223855", "title": "Modulation of the evoked release of noradrenaline in canine saphenous vein via presynaptic receptors for adenosine but not ATP.", "content": "The effects of adenosine, ATP and adenosine beta, gamma-methylene-5'-triphosphate (APPCP) were compared in the saphenous vein of the dog. Adenosine and ATP in concentrations which did not affect the response to exogenous noradrenaline, depressed that to nerve stimulation; this effect was antagonized by theophylline. APPCP increased tension in unstimulated veins and in those made to contract with noradrenaline and nerve stimulation. The results suggest that the inhibitory effect of ATP on adrenergic neurotransmission is due to its rapid breakdown to adenosine, which acts on prejunctional P1 purinoceptors.", "contents": "Modulation of the evoked release of noradrenaline in canine saphenous vein via presynaptic receptors for adenosine but not ATP. The effects of adenosine, ATP and adenosine beta, gamma-methylene-5'-triphosphate (APPCP) were compared in the saphenous vein of the dog. Adenosine and ATP in concentrations which did not affect the response to exogenous noradrenaline, depressed that to nerve stimulation; this effect was antagonized by theophylline. APPCP increased tension in unstimulated veins and in those made to contract with noradrenaline and nerve stimulation. The results suggest that the inhibitory effect of ATP on adrenergic neurotransmission is due to its rapid breakdown to adenosine, which acts on prejunctional P1 purinoceptors."}
{"id": "PMID:223856", "title": "Effect of an angiotensin converting enzyme inhibitor (SQ 14,225) on beta-adrenergic and angiotensin-induced thirsts.", "content": "The effect of acute administration of SQ 14,225, a new angiotensin converting enzyme inhibitor, on the drinking response of female rats administered either isoprenaline, angiotensin I, or angiotensin II was studied during 2 h after treatment. Administration of isoprenaline (25 micrograms/kg body wt) was accompanied by a significant increase in water intake when compared with saline-treated controls. Acute administration of a constant dose of isoprenaline (25 micrograms/kg body wt) and increasing doses of SQ 14,225 (5--50 mg/kg) was accompanied by a dose-related, linear decrease in water intake. Acute administration of either angiotensin I or angiotensin II (200 micrograms/kg body wt) was accompanied by a significant increase in water intake. The dipsogenic response to angiotensin II was not affected by acute administration of 35 mg SQ 14,225/kg body wt. However, at the same dose of SQ 14,225, angiotensin I-induced thirst was attenuated. Since isoprenaline-induced and angiotensin I-induced, but not angiotensin II-induced, thirsts are blocked by SQ 14,225, the results suggest that isoprenaline-induced thirst is mediated by way of the renin--angiotensin system.", "contents": "Effect of an angiotensin converting enzyme inhibitor (SQ 14,225) on beta-adrenergic and angiotensin-induced thirsts. The effect of acute administration of SQ 14,225, a new angiotensin converting enzyme inhibitor, on the drinking response of female rats administered either isoprenaline, angiotensin I, or angiotensin II was studied during 2 h after treatment. Administration of isoprenaline (25 micrograms/kg body wt) was accompanied by a significant increase in water intake when compared with saline-treated controls. Acute administration of a constant dose of isoprenaline (25 micrograms/kg body wt) and increasing doses of SQ 14,225 (5--50 mg/kg) was accompanied by a dose-related, linear decrease in water intake. Acute administration of either angiotensin I or angiotensin II (200 micrograms/kg body wt) was accompanied by a significant increase in water intake. The dipsogenic response to angiotensin II was not affected by acute administration of 35 mg SQ 14,225/kg body wt. However, at the same dose of SQ 14,225, angiotensin I-induced thirst was attenuated. Since isoprenaline-induced and angiotensin I-induced, but not angiotensin II-induced, thirsts are blocked by SQ 14,225, the results suggest that isoprenaline-induced thirst is mediated by way of the renin--angiotensin system."}
{"id": "PMID:223857", "title": "Changes of adrenoceptor-mediated responses in the pithed rat during propylthiouracil-induced hypothyroidism.", "content": "Adrenoceptor-mediated responses of the cardiovascular system during propylthiouracil-induced hypothyroidism were investigated. Interfering nervous reflexes could be circumvented by using pithed rats. Cardiac beta-adrenoceptor-mediated acceleration of heart rate following electrical stimulation or injection of noradrenaline and isoprenaline was markedly diminished even after 2 weeks of treatment. This loss of beta-sensitivity prevented the study of possible changes of presynaptic regulatory adrenoceptors in this test model. Taking the increase in diastolic blood pressure after application of alpha-agonists as index of the sensitivity of vascular alpha-adrenoceptors we found these to have been desensitized in the hypothyroid state. According to these results the lack of thyroid hormones exerted a similar effect on cardiac beta- and on vascular alpha-adrenoceptors.", "contents": "Changes of adrenoceptor-mediated responses in the pithed rat during propylthiouracil-induced hypothyroidism. Adrenoceptor-mediated responses of the cardiovascular system during propylthiouracil-induced hypothyroidism were investigated. Interfering nervous reflexes could be circumvented by using pithed rats. Cardiac beta-adrenoceptor-mediated acceleration of heart rate following electrical stimulation or injection of noradrenaline and isoprenaline was markedly diminished even after 2 weeks of treatment. This loss of beta-sensitivity prevented the study of possible changes of presynaptic regulatory adrenoceptors in this test model. Taking the increase in diastolic blood pressure after application of alpha-agonists as index of the sensitivity of vascular alpha-adrenoceptors we found these to have been desensitized in the hypothyroid state. According to these results the lack of thyroid hormones exerted a similar effect on cardiac beta- and on vascular alpha-adrenoceptors."}
{"id": "PMID:223858", "title": "Adrenoceptors involved in the contractile activity of islated pregnant rat uterus.", "content": "Cumulative log dose-response curves of soterenol, isoproterenol, phenylephrine and norepinephrine on isolated pregnant rat uterus at different days of gestation, were investigated. Soterenol produced a sustained inhibition of spontaneous motility during the whole pregnancy and this effect was blocked by butoxamine. The affinity of myometrium for the beta 2-adrenoceptor agonist was parallel to the concentration of progesterone in plasma during pregnancy. Isoproterenol, norepinephrine and phenylephrine caused dual, alpha- and beta-mediated responses, their relative dominance varied with the concentration and the days of pregnancy, alpha-Adrenoceptor effects of the amines coincided with increased plasma concentrations of estrogens, whereas beta ones were in parallel with the increment of plasma progesterone. It is concluded that: (a) there exist in the pregnant rat uterus beta 2-receptor-mediated responses influenced by the length of gestation; and (b) the concentration-pregnancy-dependent biphasic actions of isoproterenol, norepinephrine or phenylephrine suggest that their variable hormone-modulated ability interacts with both alpha- and beta-adrenoceptive uterine sites.", "contents": "Adrenoceptors involved in the contractile activity of islated pregnant rat uterus. Cumulative log dose-response curves of soterenol, isoproterenol, phenylephrine and norepinephrine on isolated pregnant rat uterus at different days of gestation, were investigated. Soterenol produced a sustained inhibition of spontaneous motility during the whole pregnancy and this effect was blocked by butoxamine. The affinity of myometrium for the beta 2-adrenoceptor agonist was parallel to the concentration of progesterone in plasma during pregnancy. Isoproterenol, norepinephrine and phenylephrine caused dual, alpha- and beta-mediated responses, their relative dominance varied with the concentration and the days of pregnancy, alpha-Adrenoceptor effects of the amines coincided with increased plasma concentrations of estrogens, whereas beta ones were in parallel with the increment of plasma progesterone. It is concluded that: (a) there exist in the pregnant rat uterus beta 2-receptor-mediated responses influenced by the length of gestation; and (b) the concentration-pregnancy-dependent biphasic actions of isoproterenol, norepinephrine or phenylephrine suggest that their variable hormone-modulated ability interacts with both alpha- and beta-adrenoceptive uterine sites."}
{"id": "PMID:223867", "title": "The establishment of the suspension Epstein-Barr virus producing cell lines from patients with tumoral diseases.", "content": "Isolation of the Epstein-Barr virus (EBV) in suspension lymphoblastoid cell lines from human patients with tumor diseases, mainly malignant lymphoma, has been described. It has been shown that the EBV was isolated from human patients with myeloid type of leukemia in 75% of cases. A similar virus was also isolated from patients with Hodgkin's disease and leukemoid reaction of the myeloid type for lung cancer. Morphological, cytochemical, immunological, and cytogenetic characteristics of the cell lines in which the EBV is replicated have been investigated.", "contents": "The establishment of the suspension Epstein-Barr virus producing cell lines from patients with tumoral diseases. Isolation of the Epstein-Barr virus (EBV) in suspension lymphoblastoid cell lines from human patients with tumor diseases, mainly malignant lymphoma, has been described. It has been shown that the EBV was isolated from human patients with myeloid type of leukemia in 75% of cases. A similar virus was also isolated from patients with Hodgkin's disease and leukemoid reaction of the myeloid type for lung cancer. Morphological, cytochemical, immunological, and cytogenetic characteristics of the cell lines in which the EBV is replicated have been investigated."}
{"id": "PMID:223868", "title": "Amphiphilic spectroscopic probes utilizing metal chelates.", "content": "The synthesis and initial applications are reported for 1-[p-(palmitamido)-phenyl]ethylenedinitrilotetraacetic acid. The results demonstrate the versatility of this spectroscopic probe molecule, which allows choice of a particular technique for a particular system as well as use of multiple spectroscopic techniques for complementary information about hydrophobic regions in biological systems.", "contents": "Amphiphilic spectroscopic probes utilizing metal chelates. The synthesis and initial applications are reported for 1-[p-(palmitamido)-phenyl]ethylenedinitrilotetraacetic acid. The results demonstrate the versatility of this spectroscopic probe molecule, which allows choice of a particular technique for a particular system as well as use of multiple spectroscopic techniques for complementary information about hydrophobic regions in biological systems."}
{"id": "PMID:223870", "title": "The inability of nuclear dehydrogenating clostridia to oxidize bile salt hydroxyl groups.", "content": "In a survey of the intracellular bile salt oxidoreductase activity in fecal bacteria, 16 strains of nuclear dehydrogenating clostridia and 2 strains of non-nuclear dehydrogenating C. paraputrificum were demonstrated unable to oxidize cholate at any of the 3 OH groups. Since nuclear dehydrogenation at the delta-1 and delta-4 position requires a 3-oxo precursor steroid, it appears that these organisms require the presence of a 3 alpha-hydroxysteroid dehydrogenating organism for nuclear dehydrogenation.", "contents": "The inability of nuclear dehydrogenating clostridia to oxidize bile salt hydroxyl groups. In a survey of the intracellular bile salt oxidoreductase activity in fecal bacteria, 16 strains of nuclear dehydrogenating clostridia and 2 strains of non-nuclear dehydrogenating C. paraputrificum were demonstrated unable to oxidize cholate at any of the 3 OH groups. Since nuclear dehydrogenation at the delta-1 and delta-4 position requires a 3-oxo precursor steroid, it appears that these organisms require the presence of a 3 alpha-hydroxysteroid dehydrogenating organism for nuclear dehydrogenation."}
{"id": "PMID:223871", "title": "Increase in Na+, K+ -ATPase enzyme units in liver and kidneys from essential fatty acid deficient rats.", "content": "(3H)-Ouabain binding to liver and kidney preparations was utilized to estimate the number of Na+, K+-ATPase enzyme units in livers and kidneys from rats fed 2% corn oil supplemented or fat-free diets. The specific (3H)-ouabain binding in liver and kidney preparations from fatty acid deficient rats was increased approximately 40%, but the affinity of the binding sites for ouabain (Kd-value) remained unchanged. The increased concentration of Na+, K+-ATPase enzyme units observed in the essential fatty acid deficient rats may contribute to the reduced body fat accumulation and elevated heat production observed in these animals.", "contents": "Increase in Na+, K+ -ATPase enzyme units in liver and kidneys from essential fatty acid deficient rats. (3H)-Ouabain binding to liver and kidney preparations was utilized to estimate the number of Na+, K+-ATPase enzyme units in livers and kidneys from rats fed 2% corn oil supplemented or fat-free diets. The specific (3H)-ouabain binding in liver and kidney preparations from fatty acid deficient rats was increased approximately 40%, but the affinity of the binding sites for ouabain (Kd-value) remained unchanged. The increased concentration of Na+, K+-ATPase enzyme units observed in the essential fatty acid deficient rats may contribute to the reduced body fat accumulation and elevated heat production observed in these animals."}
{"id": "PMID:223872", "title": "Effect of acetone on VLDL secretion by the isolated rat liver.", "content": "High acetone levels occur in uncontrolled diabetes and after isopropanol administration to rats. In both conditions, very low density lipoproteins (VLDL) secretion is depressed. Acetone, hoever, failed to affect the VLDL secretion rate by the isolated perfused rat liver, suggesting that this metabolite is not involved in impaired VLDL production in diabetes and after isopropanol administration.", "contents": "Effect of acetone on VLDL secretion by the isolated rat liver. High acetone levels occur in uncontrolled diabetes and after isopropanol administration to rats. In both conditions, very low density lipoproteins (VLDL) secretion is depressed. Acetone, hoever, failed to affect the VLDL secretion rate by the isolated perfused rat liver, suggesting that this metabolite is not involved in impaired VLDL production in diabetes and after isopropanol administration."}
{"id": "PMID:223873", "title": "Absence of dopamine sensitive adenylate cyclase in the A10 region, the origin of mesolimbic dopamine neurones.", "content": "Dopamine (DA) failed to stimulate the adenylate cyclase of the mesolimbic A10 DA nerve cell body area, in contrast to tis activating effect in the nigrostriatal A9 DA cell body area. The enzyme was stimulated by GMPPNP (a GTP analog) and NaF. This indicates the absence in the A 10 cell area of DA receptors with functional coupling on adenylate cyclase, in contrast to the A9 cell area where such DA receptors are believed to be located on afferent axon terminals.", "contents": "Absence of dopamine sensitive adenylate cyclase in the A10 region, the origin of mesolimbic dopamine neurones. Dopamine (DA) failed to stimulate the adenylate cyclase of the mesolimbic A10 DA nerve cell body area, in contrast to tis activating effect in the nigrostriatal A9 DA cell body area. The enzyme was stimulated by GMPPNP (a GTP analog) and NaF. This indicates the absence in the A 10 cell area of DA receptors with functional coupling on adenylate cyclase, in contrast to the A9 cell area where such DA receptors are believed to be located on afferent axon terminals."}
{"id": "PMID:223874", "title": "Inverse regulation of spore germination and growth by cyclic AMP in Streptomyces hygroscopicus.", "content": "The cyclic AMP level in germinating spores of Streptomyces hygroscopicus rises to a miximum ag outgrowth of germ tubes. Exogenous cyclic AMP results in an inverse effect on germination speed and growth.", "contents": "Inverse regulation of spore germination and growth by cyclic AMP in Streptomyces hygroscopicus. The cyclic AMP level in germinating spores of Streptomyces hygroscopicus rises to a miximum ag outgrowth of germ tubes. Exogenous cyclic AMP results in an inverse effect on germination speed and growth."}
{"id": "PMID:223875", "title": "Activation of the electrogenic Na-pump of cardiac muscle fibres by ACh in K-free solutions.", "content": "The ionic mechanism of the membrane outward current (ACh-current) of bullfrog atrium muscle, induced by acetylcholine in K-free solution, was analyzed by a voltage-clamp experiment. The results suggested that the ACh-current was induced not only by an increase in K-conductance but also by an activation of the electrogenic Na-pump.", "contents": "Activation of the electrogenic Na-pump of cardiac muscle fibres by ACh in K-free solutions. The ionic mechanism of the membrane outward current (ACh-current) of bullfrog atrium muscle, induced by acetylcholine in K-free solution, was analyzed by a voltage-clamp experiment. The results suggested that the ACh-current was induced not only by an increase in K-conductance but also by an activation of the electrogenic Na-pump."}
{"id": "PMID:223876", "title": "Depression of spontaneous and ionophore-induced neurotransmitter release by Salmonella.", "content": "Exposure of frog neuromuscular junctions to heat-killed, lyophilized Salmonella typhimurium (SR 11) produces an early increase in spontaneous transmitter release followed by depression of release and blockade of the obligatory release usually induced by ionophore X537A.", "contents": "Depression of spontaneous and ionophore-induced neurotransmitter release by Salmonella. Exposure of frog neuromuscular junctions to heat-killed, lyophilized Salmonella typhimurium (SR 11) produces an early increase in spontaneous transmitter release followed by depression of release and blockade of the obligatory release usually induced by ionophore X537A."}
{"id": "PMID:223877", "title": "On the action of vitamin C on the neuromuscular junctions.", "content": "High concentrations of ascorbic acid produce complete blockage of the transmission of nervous stimuli on the isolated neuromuscular preparation of phrenic nerve-hemidiaphragm of the rat.", "contents": "On the action of vitamin C on the neuromuscular junctions. High concentrations of ascorbic acid produce complete blockage of the transmission of nervous stimuli on the isolated neuromuscular preparation of phrenic nerve-hemidiaphragm of the rat."}
{"id": "PMID:223887", "title": "Spermatogenesis in men exposed to polybrominated biphenyl (PBB).", "content": "Experience with other halogenated hydrocarbons, animal experiments, and individual complaints indicated that polybrominated biphenyl (PBB) might have an effect on human spermatogenesis. Analysis of semen from 52 PBB-exposed men as compared with analysis of semen from a control group of 52 men not exposed to PBB revealed no differences in the distribution of sperm counts, motility, or morphology.", "contents": "Spermatogenesis in men exposed to polybrominated biphenyl (PBB). Experience with other halogenated hydrocarbons, animal experiments, and individual complaints indicated that polybrominated biphenyl (PBB) might have an effect on human spermatogenesis. Analysis of semen from 52 PBB-exposed men as compared with analysis of semen from a control group of 52 men not exposed to PBB revealed no differences in the distribution of sperm counts, motility, or morphology."}
{"id": "PMID:223888", "title": "Initiation of hamster sperm motility from quiescence: effect of conditions upon flagellation and respiration.", "content": "The point within the male reproductive tract where sperm motility originates varies with mammalian species. Premotile sperm from hamster, a species whose sperm are still quiescent in the epididymis, were used here to investigate further the parameters involved in the initiation of sperm motility. Two types of motility were produced: (1) partial, weak flagellation by simple dilution; (2) strong, complete motility by inducers (calcium, cyclic adenosine 3':5'-monophosphate) in the presence of amplifiers (caffeine, spermine). Expansion of initiation conditions to test tube volumes revealed that, at high sperm dilutions, bicarbonate could also induce motility. The respiratory consequences of sperm motility induction were measured. A Large, short-term burst of oxygen consumption occurred at a time paralleling the previously reported shifts in nucleotide levels associated with this event.", "contents": "Initiation of hamster sperm motility from quiescence: effect of conditions upon flagellation and respiration. The point within the male reproductive tract where sperm motility originates varies with mammalian species. Premotile sperm from hamster, a species whose sperm are still quiescent in the epididymis, were used here to investigate further the parameters involved in the initiation of sperm motility. Two types of motility were produced: (1) partial, weak flagellation by simple dilution; (2) strong, complete motility by inducers (calcium, cyclic adenosine 3':5'-monophosphate) in the presence of amplifiers (caffeine, spermine). Expansion of initiation conditions to test tube volumes revealed that, at high sperm dilutions, bicarbonate could also induce motility. The respiratory consequences of sperm motility induction were measured. A Large, short-term burst of oxygen consumption occurred at a time paralleling the previously reported shifts in nucleotide levels associated with this event."}
{"id": "PMID:223893", "title": "The effect of sulfhydryl and amino group reagents on human lymphocyte--sheep erythrocyte rosettes.", "content": "We have studied the influence of certain chemical groups, located on the surface of lymphocytes or sheep red blood cells, on the ability of these cells to form spontaneous rosettes. We found that fluorescamine, which reacts with amino groups, inhibits rosette formation, while p-chloromercuriphenylsulfonic acid, which binds to sulfydryl groups, increases the percentage of the rosette-forming lymphocytes. The possible mechanism of action of the above reagents is discussed.", "contents": "The effect of sulfhydryl and amino group reagents on human lymphocyte--sheep erythrocyte rosettes. We have studied the influence of certain chemical groups, located on the surface of lymphocytes or sheep red blood cells, on the ability of these cells to form spontaneous rosettes. We found that fluorescamine, which reacts with amino groups, inhibits rosette formation, while p-chloromercuriphenylsulfonic acid, which binds to sulfydryl groups, increases the percentage of the rosette-forming lymphocytes. The possible mechanism of action of the above reagents is discussed."}
{"id": "PMID:223894", "title": "Cytologic uniformity of breast cancer from different localizations: a pattern analysis study.", "content": "Using cytologic pattern analysis it is shown that regions of different histologic structure in one breast cancer are of cytologic homogeneity. The so-called PFORM -- the quotient of the total outline length of DNA-particles to the nuclear area -- gives an objective cytologic parameter which is independent of DNA content of cancer cells. This objective parameter together with the subjective cytologic parameters described earlier may be a better basis for describing the biologic behavior of breast cancer than histologic structure which is inhomogeneous very often in a lump.", "contents": "Cytologic uniformity of breast cancer from different localizations: a pattern analysis study. Using cytologic pattern analysis it is shown that regions of different histologic structure in one breast cancer are of cytologic homogeneity. The so-called PFORM -- the quotient of the total outline length of DNA-particles to the nuclear area -- gives an objective cytologic parameter which is independent of DNA content of cancer cells. This objective parameter together with the subjective cytologic parameters described earlier may be a better basis for describing the biologic behavior of breast cancer than histologic structure which is inhomogeneous very often in a lump."}
{"id": "PMID:223898", "title": "Filipin prevents and reverses insulin stimulation of rat adipocyte phosphodiesterase.", "content": "A membrane fraction prepared from isolated rat adipocytes contained an insulin-sensitive cyclic nucleotide phosphodiesterase (EC 3.1.4.17) which catalyzed the hydrolysis of both adenosine 3',5'-monophosphate (cAMP) and guanosine 3',5'-monophosphate (cGMP). The rate of hydrolysis of cGMP was about one-third that of cAMP. The hydrolysis of the two nucleotides appeared to be assoicated with one catalytic site: one nucleotide interfered with the hydrolysis of the other, in a manner predictable from the kinetic constants in that the Km of one nucleotide as a substrate was comparable to its Ki as an inhibitor of the hydrolysis of the other nucleotide. Incubation of the adipocytes with insulin increased the Vmax of phosphodiesterase without affecting the Km values for either substrate. After adipocytes had been treated with filipin, a membrane perturbant, at a concentration that did not cause cell lysis, the response of phosphodiesterase to insulin was obliterated. Further, the insulin-stimulated phosphodiesterase activity was reversed when hormone-treated cells were subsequently incubated with this agent. These results suggest that the response of membrane phosphodiesterase to insulin is impaired once adipocytes have been exposed to filipin, either preceding or following the incubation with insulin.", "contents": "Filipin prevents and reverses insulin stimulation of rat adipocyte phosphodiesterase. A membrane fraction prepared from isolated rat adipocytes contained an insulin-sensitive cyclic nucleotide phosphodiesterase (EC 3.1.4.17) which catalyzed the hydrolysis of both adenosine 3',5'-monophosphate (cAMP) and guanosine 3',5'-monophosphate (cGMP). The rate of hydrolysis of cGMP was about one-third that of cAMP. The hydrolysis of the two nucleotides appeared to be assoicated with one catalytic site: one nucleotide interfered with the hydrolysis of the other, in a manner predictable from the kinetic constants in that the Km of one nucleotide as a substrate was comparable to its Ki as an inhibitor of the hydrolysis of the other nucleotide. Incubation of the adipocytes with insulin increased the Vmax of phosphodiesterase without affecting the Km values for either substrate. After adipocytes had been treated with filipin, a membrane perturbant, at a concentration that did not cause cell lysis, the response of phosphodiesterase to insulin was obliterated. Further, the insulin-stimulated phosphodiesterase activity was reversed when hormone-treated cells were subsequently incubated with this agent. These results suggest that the response of membrane phosphodiesterase to insulin is impaired once adipocytes have been exposed to filipin, either preceding or following the incubation with insulin."}
{"id": "PMID:223899", "title": "Inhibition by estradiol-17 beta of porcine thecal androgen production in vitro.", "content": "Thecal preparations from medium-sized procine ovarian follicles (3.5-5 mm diameter) were incubated for 4 h in a chemically defined medium in the presence or absence of highly purified luteinizing hormone (LH) and/or estradiol-17 beta (estradiol). LH (1 microgram/ml) stimulated the thecal production of testosterone (T) and dihydrotestosterone (DHT) by 2- to 3-fold. Although estradiol (10 microgram/ml) alone had only a slight but non-significant inhibitory effect on basal testosterone production, it significantly inhibited the  production of both T and DHT as well as decreasing the DHT/T ratio in a dose-related manner in the presence of LH. Production of cyclic adenosine 3',5'-monophosphate (cAMP) and progesterone by the thecal cells was stimulated 50-to 200-fold and 2.5-fold, respectively, by LH. Estradiol had no significant effect on thecal cAMP and progesterone production in the presence or absence of the gonadotropin. These findings are consistent with the concept that estradiol produced by granulosa cells following hormonal stimulation may serve as a local negative feedback mechanism to control thecal androgen production.", "contents": "Inhibition by estradiol-17 beta of porcine thecal androgen production in vitro. Thecal preparations from medium-sized procine ovarian follicles (3.5-5 mm diameter) were incubated for 4 h in a chemically defined medium in the presence or absence of highly purified luteinizing hormone (LH) and/or estradiol-17 beta (estradiol). LH (1 microgram/ml) stimulated the thecal production of testosterone (T) and dihydrotestosterone (DHT) by 2- to 3-fold. Although estradiol (10 microgram/ml) alone had only a slight but non-significant inhibitory effect on basal testosterone production, it significantly inhibited the  production of both T and DHT as well as decreasing the DHT/T ratio in a dose-related manner in the presence of LH. Production of cyclic adenosine 3',5'-monophosphate (cAMP) and progesterone by the thecal cells was stimulated 50-to 200-fold and 2.5-fold, respectively, by LH. Estradiol had no significant effect on thecal cAMP and progesterone production in the presence or absence of the gonadotropin. These findings are consistent with the concept that estradiol produced by granulosa cells following hormonal stimulation may serve as a local negative feedback mechanism to control thecal androgen production."}
{"id": "PMID:223900", "title": "Hormonal regulation of thyroidal protein phosphokinase activities. II. Differential sensitivity of type I and type II cAMP-dependent enzymes to the treatment of rats with thyroxine.", "content": "Two cAMP-dependent protein kinase activities can be separated from rat thyroid cytosol. Their elution properties during the gel chromatography, as well as their sedimentation coefficients after sucrose-gradient ultracentrifugation and their capacity to dissociate in the presence of histones, suggest they are like the Type I and Type II protein kinases described in many other tissues. The sensitivity of the two types of kinases to thyroxine treatment is different. The activity of Type I is not changed during the first 5 days of treatment. Thereafter, it decreased by about 50% and is maintained at that level for up to one month. The activity of the Type II enzyme decreased rapidly by about 30-40% already on the second day of treatment, and after 10 days it reached 50% of the initial level. This differential reactivity of the two types of enzymes to the thyroxine treatment leads to profound modifications in their relative activities between the second and the fifth day of treatment. The significance of these results and the possible role of the two types of kinases in the control of different steps of iodine metabolism have been discussed.", "contents": "Hormonal regulation of thyroidal protein phosphokinase activities. II. Differential sensitivity of type I and type II cAMP-dependent enzymes to the treatment of rats with thyroxine. Two cAMP-dependent protein kinase activities can be separated from rat thyroid cytosol. Their elution properties during the gel chromatography, as well as their sedimentation coefficients after sucrose-gradient ultracentrifugation and their capacity to dissociate in the presence of histones, suggest they are like the Type I and Type II protein kinases described in many other tissues. The sensitivity of the two types of kinases to thyroxine treatment is different. The activity of Type I is not changed during the first 5 days of treatment. Thereafter, it decreased by about 50% and is maintained at that level for up to one month. The activity of the Type II enzyme decreased rapidly by about 30-40% already on the second day of treatment, and after 10 days it reached 50% of the initial level. This differential reactivity of the two types of enzymes to the thyroxine treatment leads to profound modifications in their relative activities between the second and the fifth day of treatment. The significance of these results and the possible role of the two types of kinases in the control of different steps of iodine metabolism have been discussed."}
{"id": "PMID:223901", "title": "Evidence for the involvement of lutropin-independent RNA synthesis in Leydig cell steroidogenesis.", "content": "The effect of incubating purified Leydig cells in Eagle's medium and the subsequent effect of the RNA synthesis inhibitors, actinomycin D and cordycepin, on lutropin-stimulated testosterone synthesis have been investigated. The inhibiting effect was found to be inversely related to the time of preincubation; with cells preincubated for 0, 1, 2 and 3 h with Eagle's medium only, followed by 2-h incubation with lutropin with and without actinomycin D, testosterone synthesis was inhibited by 37 +/- 4, 31 +/- 3, 18 +/- 4 and 14 +/- 3% respectively (means +/- s.e.m., n = 5). In cells that had been preincubated for 3 h there was no significant effect of actinomycin D on testosterone synthesis during the first hour of incubation with lutropin. Thereafter the inhibition increased with time reaching a maximum of 30% after 5 h. The effects of preincubation were not due to endogenous lutropin in the Leydig cells because cells isolated from hypophysectomized rats gave similar results. The inhibition of [3H]uridine incorporation into the Leydig cell RNA was 80 +/- 1% with 8 microgram/ml actinomycin D. Increasing the concentration of this inhibitor to 80 microgram/ml did not significantly increase the inhibition of [3H]uridine incorporation or lutropin-stimulated steroidogenesis in preincubated and non-preincubated cells. With cordycepin the inhibition of both RNA synthesis and lutropin-stimulated testosterone synthesis in non-preincubated cells were the same; with 25.1--251 microgram/ml approx. 30--70% resp. With preincubated cells (3 h), 0--50% inhibition of testosterone synthesis was obtained respectively. The inhibitory effect of actinomycin D oimilar to that obtained with lutropin. These observations suggest that during preincubation and independently of lutropin, synthesis of intermediates, including RNAs required for stimulation of steroidogenesis, takes place and that subsequent stimulation of steroidogenesis by lutropin occurs without further de novo RNA synthesis. These results provide evidence for a permissive role of specific RNA and protein synthesis in the action of lutropin on testosterone synthesis in the Leydig cell.", "contents": "Evidence for the involvement of lutropin-independent RNA synthesis in Leydig cell steroidogenesis. The effect of incubating purified Leydig cells in Eagle's medium and the subsequent effect of the RNA synthesis inhibitors, actinomycin D and cordycepin, on lutropin-stimulated testosterone synthesis have been investigated. The inhibiting effect was found to be inversely related to the time of preincubation; with cells preincubated for 0, 1, 2 and 3 h with Eagle's medium only, followed by 2-h incubation with lutropin with and without actinomycin D, testosterone synthesis was inhibited by 37 +/- 4, 31 +/- 3, 18 +/- 4 and 14 +/- 3% respectively (means +/- s.e.m., n = 5). In cells that had been preincubated for 3 h there was no significant effect of actinomycin D on testosterone synthesis during the first hour of incubation with lutropin. Thereafter the inhibition increased with time reaching a maximum of 30% after 5 h. The effects of preincubation were not due to endogenous lutropin in the Leydig cells because cells isolated from hypophysectomized rats gave similar results. The inhibition of [3H]uridine incorporation into the Leydig cell RNA was 80 +/- 1% with 8 microgram/ml actinomycin D. Increasing the concentration of this inhibitor to 80 microgram/ml did not significantly increase the inhibition of [3H]uridine incorporation or lutropin-stimulated steroidogenesis in preincubated and non-preincubated cells. With cordycepin the inhibition of both RNA synthesis and lutropin-stimulated testosterone synthesis in non-preincubated cells were the same; with 25.1--251 microgram/ml approx. 30--70% resp. With preincubated cells (3 h), 0--50% inhibition of testosterone synthesis was obtained respectively. The inhibitory effect of actinomycin D oimilar to that obtained with lutropin. These observations suggest that during preincubation and independently of lutropin, synthesis of intermediates, including RNAs required for stimulation of steroidogenesis, takes place and that subsequent stimulation of steroidogenesis by lutropin occurs without further de novo RNA synthesis. These results provide evidence for a permissive role of specific RNA and protein synthesis in the action of lutropin on testosterone synthesis in the Leydig cell."}
{"id": "PMID:223902", "title": "Differential effects of castration and testosterone replacement on basal and LHRH-stimulated cAMP and cGMP accumulation and on gonadotropin release from the pituitary of the male rat.", "content": "Castration of male rats decreased cAMP levels, and increased cGMP levels and gonadotropin release from anterior pituitaries incubated in vitro. Testosterone (T) replacement via silastic tubes filled with the steroid increased cAMP and decreased cGMP levels and gonadotropin release. Incubation of hemipituitaries from intact males with luteinizing hormone releasing hormone (LHRH, 5 nM for 2 h) resulted in increased cAMP and cGMP accumulation and gonadotropin release. Castration abolished LHRH-induced cAMP accumulation, but increased the effect of LHRH on cGMP accumulation and gonadotropin release. Testosterone replacement restored cAMP stimulation by LHRH but decreased LHRH-induced elevation of cGMP levels and gonadotropin release. These data illustrate parallel increases by castration of LHRH-induced cGMP accumulation and of gonadotropin release. Furthermore, these two parameters are influenced in the opposite direction by replacement therapy. These results support the concept of a role for cGMP in LHRH action as well as providing evidence of a link between the feedback action of T and cGMP in the pituitary gland.", "contents": "Differential effects of castration and testosterone replacement on basal and LHRH-stimulated cAMP and cGMP accumulation and on gonadotropin release from the pituitary of the male rat. Castration of male rats decreased cAMP levels, and increased cGMP levels and gonadotropin release from anterior pituitaries incubated in vitro. Testosterone (T) replacement via silastic tubes filled with the steroid increased cAMP and decreased cGMP levels and gonadotropin release. Incubation of hemipituitaries from intact males with luteinizing hormone releasing hormone (LHRH, 5 nM for 2 h) resulted in increased cAMP and cGMP accumulation and gonadotropin release. Castration abolished LHRH-induced cAMP accumulation, but increased the effect of LHRH on cGMP accumulation and gonadotropin release. Testosterone replacement restored cAMP stimulation by LHRH but decreased LHRH-induced elevation of cGMP levels and gonadotropin release. These data illustrate parallel increases by castration of LHRH-induced cGMP accumulation and of gonadotropin release. Furthermore, these two parameters are influenced in the opposite direction by replacement therapy. These results support the concept of a role for cGMP in LHRH action as well as providing evidence of a link between the feedback action of T and cGMP in the pituitary gland."}
{"id": "PMID:223903", "title": "Effects of calcium and cyclic nucleotides on rat calcitonin and parathyroid hormone secretion.", "content": "Recently we developed a system for studying concurrent secretion of calcitonin (CT)and parathyroid hormone(PTH)in vitro from single rat thyroparathyroid gland complexes. In the present study, mechanisms involved in secretion of CT and PTH were explored by altering the medium [Ca ] and by using the Ca antagonist, verapamil. We also re-examined the idea that cyclic nucleotides may help regulate secretion of these hormones and attempted to determine if effects of cyclic nucleotides might be altered by changes in medium [Ca]. Thyroparathyroid glands from 8-day-old rats were incubated in serum-free medium for 8h, and CT and PTH levels in the medium were measured by radioimmunoassays. We show for the first time that: (1) although low [Ca] is well known to promote PTH release, some extracellular Ca is needed for PTH secretion to occur at a maximal rate; (2) inhibition of Ca entry into cells with verapamil mimics the effects of low medium Ca on both CT and PTH release; and (3) cyclic nucleotides may exert their effects on secretion of CT and PTH at least in part via effects on Ca entry into cells.", "contents": "Effects of calcium and cyclic nucleotides on rat calcitonin and parathyroid hormone secretion. Recently we developed a system for studying concurrent secretion of calcitonin (CT)and parathyroid hormone(PTH)in vitro from single rat thyroparathyroid gland complexes. In the present study, mechanisms involved in secretion of CT and PTH were explored by altering the medium [Ca ] and by using the Ca antagonist, verapamil. We also re-examined the idea that cyclic nucleotides may help regulate secretion of these hormones and attempted to determine if effects of cyclic nucleotides might be altered by changes in medium [Ca]. Thyroparathyroid glands from 8-day-old rats were incubated in serum-free medium for 8h, and CT and PTH levels in the medium were measured by radioimmunoassays. We show for the first time that: (1) although low [Ca] is well known to promote PTH release, some extracellular Ca is needed for PTH secretion to occur at a maximal rate; (2) inhibition of Ca entry into cells with verapamil mimics the effects of low medium Ca on both CT and PTH release; and (3) cyclic nucleotides may exert their effects on secretion of CT and PTH at least in part via effects on Ca entry into cells."}
{"id": "PMID:223905", "title": "Experiences of vaccination with inactivated poliovirus vaccine and epidemiology round a single case of polio in 1977 in Sweden.", "content": "Inactivated poliovaccine manufactured in this country has been used in Sweden since 1957. The coverage of the vaccination in children is close to 100%. The majority of adults has also been immunized. No indigenous case occurred between 1962 and 1977. In 1977 a 2-year-old unvaccinated girl caught a mild paralytic disease caused by polio type 2. An epidemiologic investigation revealed excretion of virus in 25 persons, all close contacts to other excretors. No virus excretors were found among vaccinated pre-school children while 14 of 20 unvaccinated children showed positive virus samples.", "contents": "Experiences of vaccination with inactivated poliovirus vaccine and epidemiology round a single case of polio in 1977 in Sweden. Inactivated poliovaccine manufactured in this country has been used in Sweden since 1957. The coverage of the vaccination in children is close to 100%. The majority of adults has also been immunized. No indigenous case occurred between 1962 and 1977. In 1977 a 2-year-old unvaccinated girl caught a mild paralytic disease caused by polio type 2. An epidemiologic investigation revealed excretion of virus in 25 persons, all close contacts to other excretors. No virus excretors were found among vaccinated pre-school children while 14 of 20 unvaccinated children showed positive virus samples."}
{"id": "PMID:223906", "title": "The efficacy of polio vaccination in Finland.", "content": "The inactivated polio vaccine has eliminated not only the disease but also polioviruses from Finland. The last endemic cases of poliomyelitis were seen in 1961, and two were imported in 1964. To check whether polioviruses were still circulating in Finland, an intensified search for polioviruses was carried out in 1972-1974 in sewage, among patients with polio-like diseases and among healthy preschool children. Viruses, mostly Coxsackie B viruses, were isolated from sewage in 67% of the samples, but no polioviruses. The etiology of aseptic meningitis and other polio-like diseases was explained in 52% of the cases, but without isolation of any polioviruses. Faeces samples from 4878 different preschool children were examined: 15.7% of them excreted viruses, but not polioviruses.", "contents": "The efficacy of polio vaccination in Finland. The inactivated polio vaccine has eliminated not only the disease but also polioviruses from Finland. The last endemic cases of poliomyelitis were seen in 1961, and two were imported in 1964. To check whether polioviruses were still circulating in Finland, an intensified search for polioviruses was carried out in 1972-1974 in sewage, among patients with polio-like diseases and among healthy preschool children. Viruses, mostly Coxsackie B viruses, were isolated from sewage in 67% of the samples, but no polioviruses. The etiology of aseptic meningitis and other polio-like diseases was explained in 52% of the cases, but without isolation of any polioviruses. Faeces samples from 4878 different preschool children were examined: 15.7% of them excreted viruses, but not polioviruses."}
{"id": "PMID:223907", "title": "Poliomyelitis survey in Middle-East countries.", "content": "The poliomyelitis survey was started in 1976 in Bahrain and Kuwait. For each paralytic case, diagnosis was done by virus isolation, neutralizing antibody titration and specific IgM characterization. More than 90% of the infants who were ill were less than 2 years old. In Bahrain, 17 paralytic cases in 1976 and 12 in 1977 occurred between January and July (annual incidence was respectively 7.7 and 5.4/100,000). The first epidemic was due to poliovirus type 2, the second one to poliovirus type1. From 29 cases, 13 occurred in vaccinated infants of which 9 received 3 or 4 oral vaccine doses. For 3 infants, paralysis occurred less than one month after vaccination. All the isolates were wild polioviruses (rct). In Kuwait, 119 cases were examined, and of them, 57 occurred between August 76 and May 77 (incidence 5.7/100,000). Poliovirus type 1 was responsible for 61% of cases, type 2 for 5% and type 3 for 12%. From October 1976 to December 1977, 350 stools samples were collected from contacts: 19% of them carried poliovirus (12% type 1, 1% type 2 and 6% type 3). All the viruses isolated from both paralytic cases and contacts were wild strains (rct). Of 119 cases, 35 occurred in vaccinated infants from which 4 had received 3 or 4 oral vaccine doses. For 11 infants paralysis occurred less than one month after vaccination. The virus spread was evaluated (i) just before vaccination in 337 infants or children from June to December 76: 8% carried poliovirus Sabin-like strains (and 18% non polioviruses), and (ii) one month after vaccination in 75 infants: 37% carried poliovirus Sabin-like strains.", "contents": "Poliomyelitis survey in Middle-East countries. The poliomyelitis survey was started in 1976 in Bahrain and Kuwait. For each paralytic case, diagnosis was done by virus isolation, neutralizing antibody titration and specific IgM characterization. More than 90% of the infants who were ill were less than 2 years old. In Bahrain, 17 paralytic cases in 1976 and 12 in 1977 occurred between January and July (annual incidence was respectively 7.7 and 5.4/100,000). The first epidemic was due to poliovirus type 2, the second one to poliovirus type1. From 29 cases, 13 occurred in vaccinated infants of which 9 received 3 or 4 oral vaccine doses. For 3 infants, paralysis occurred less than one month after vaccination. All the isolates were wild polioviruses (rct). In Kuwait, 119 cases were examined, and of them, 57 occurred between August 76 and May 77 (incidence 5.7/100,000). Poliovirus type 1 was responsible for 61% of cases, type 2 for 5% and type 3 for 12%. From October 1976 to December 1977, 350 stools samples were collected from contacts: 19% of them carried poliovirus (12% type 1, 1% type 2 and 6% type 3). All the viruses isolated from both paralytic cases and contacts were wild strains (rct). Of 119 cases, 35 occurred in vaccinated infants from which 4 had received 3 or 4 oral vaccine doses. For 11 infants paralysis occurred less than one month after vaccination. The virus spread was evaluated (i) just before vaccination in 337 infants or children from June to December 76: 8% carried poliovirus Sabin-like strains (and 18% non polioviruses), and (ii) one month after vaccination in 75 infants: 37% carried poliovirus Sabin-like strains."}
{"id": "PMID:223908", "title": "New approach to the production of concentrated and purified inactivated polio and rabies tissue culture vaccines.", "content": "The preparation of inactivated polio and rabies vaccine in tissue culture has been developed into a \"Unit Process\" at our laboratory during recent years. The process comprises trypsinization of animal kidney cells by the perfusion method, cell/virus cultivation in microcarrier culture and concentration and purification of the virus suspension followed by inactivation. Also, the control tests on the virus suspensions and vaccines are performed, to the greatest possible extent, according to the same procedures. In the meantime, both vaccines thus prepared have been tested in man. High antibody titres have been obtained and no adverse reactions have been observed. The results of a field trial with inactivated poliovaccine, administered at different concentrations, will be presented by Dr Salk. Preliminary concepts for further development of the production and control of these inactivated virus vaccines are discussed.", "contents": "New approach to the production of concentrated and purified inactivated polio and rabies tissue culture vaccines. The preparation of inactivated polio and rabies vaccine in tissue culture has been developed into a \"Unit Process\" at our laboratory during recent years. The process comprises trypsinization of animal kidney cells by the perfusion method, cell/virus cultivation in microcarrier culture and concentration and purification of the virus suspension followed by inactivation. Also, the control tests on the virus suspensions and vaccines are performed, to the greatest possible extent, according to the same procedures. In the meantime, both vaccines thus prepared have been tested in man. High antibody titres have been obtained and no adverse reactions have been observed. The results of a field trial with inactivated poliovaccine, administered at different concentrations, will be presented by Dr Salk. Preliminary concepts for further development of the production and control of these inactivated virus vaccines are discussed."}
{"id": "PMID:223909", "title": "Vaccination against pox diseases under immunosuppressive conditions.", "content": "Pox diseases, caused either by smallpox virus or zoonotic pox viruses or animals, continue to be of potential danger to a non-vaccinated population. Mass vaccinations will become necessary and will then also be administered to persons with immunological aberrations. The vaccines which are presently used against smallpox cause severe complications in such hosts. In contrast, the attenuated vaccinia virus strain MVA is safe even under the conditions of immunosuppression and is recommended for the production of smallpox vaccines. Because of the special epizootic situations and the numerous immunosuppressive factors present in developing countries, the use of such a safe pox vaccine there is of crucial importance.", "contents": "Vaccination against pox diseases under immunosuppressive conditions. Pox diseases, caused either by smallpox virus or zoonotic pox viruses or animals, continue to be of potential danger to a non-vaccinated population. Mass vaccinations will become necessary and will then also be administered to persons with immunological aberrations. The vaccines which are presently used against smallpox cause severe complications in such hosts. In contrast, the attenuated vaccinia virus strain MVA is safe even under the conditions of immunosuppression and is recommended for the production of smallpox vaccines. Because of the special epizootic situations and the numerous immunosuppressive factors present in developing countries, the use of such a safe pox vaccine there is of crucial importance."}
{"id": "PMID:223910", "title": "Subcellular fractions for immunizing against pertussis.", "content": "Differential centrifugation was used to prepare fractions from broken cells of Bordetella pertussis strain 114. Whole cells and several fractions were then assayed for potency and for safety. Crude ribosomal fractions were uniformly protective. However, ribosomes purified by washing in high salt solution and recentrifugation were at least 40 fold less potent. Protective antigen was found in the wash fluid. Wash fluid was subjected to SDS-polyacrylamide gel electrophoresis. No specific protein or carbohydrate has yet been identified as a protective immunogen. It is clear that ribosomes are not protective, but copurify with protective antigen. SDS-polyacrylamide gel analysis of soluble material purified from ribosomes may be of value in experimental studies on pertussis vaccine. If the protective immunogen can be identified, this procedure may also be of value in vaccine standardization.", "contents": "Subcellular fractions for immunizing against pertussis. Differential centrifugation was used to prepare fractions from broken cells of Bordetella pertussis strain 114. Whole cells and several fractions were then assayed for potency and for safety. Crude ribosomal fractions were uniformly protective. However, ribosomes purified by washing in high salt solution and recentrifugation were at least 40 fold less potent. Protective antigen was found in the wash fluid. Wash fluid was subjected to SDS-polyacrylamide gel electrophoresis. No specific protein or carbohydrate has yet been identified as a protective immunogen. It is clear that ribosomes are not protective, but copurify with protective antigen. SDS-polyacrylamide gel analysis of soluble material purified from ribosomes may be of value in experimental studies on pertussis vaccine. If the protective immunogen can be identified, this procedure may also be of value in vaccine standardization."}
{"id": "PMID:223911", "title": "Serodiagnosis of herpesvirus infection in primates.", "content": "The presence of herpesviruses in various animal tissues used for vaccine production is of importance, inasmuch as these viruses may go unrecognized, residing in latent form. Of greatest concern is Herpesvirus simiae (B virus) present in the majority of macaca species, one of the more extensively used laboratory nonhuman primates. The close antigenic relationship of B virus to human herpes strains (H. hominis) and SA8 (a baboon herpesvirus) makes serologic differentiation extremely difficult, but necessary. Complicating the differential diagnosis is the frequent infection of simian species with human strains. The present study clearly shows that many animal sera negative to herpes simplex will be negative to B virus in the neutralization test. However, a sufficient number of sera will be negative to simplex, but positive to B virus, indicating that the assumed one-way cross is invalid. Also, if antibody to simplex is present, and this antibody is present in most adult macaques, then differentiation requires testing with B virus. At least 50% of these positive sera may appear to be negative for B virus if only tested with H. hominis. Approximately 25% of the remaining positive sera will have higher titers to B virus than to herpes simplex and 25% will have the same titers to both viruses. Further, complement is required by many of the test sera to detect the presence of antibodies to B virus.", "contents": "Serodiagnosis of herpesvirus infection in primates. The presence of herpesviruses in various animal tissues used for vaccine production is of importance, inasmuch as these viruses may go unrecognized, residing in latent form. Of greatest concern is Herpesvirus simiae (B virus) present in the majority of macaca species, one of the more extensively used laboratory nonhuman primates. The close antigenic relationship of B virus to human herpes strains (H. hominis) and SA8 (a baboon herpesvirus) makes serologic differentiation extremely difficult, but necessary. Complicating the differential diagnosis is the frequent infection of simian species with human strains. The present study clearly shows that many animal sera negative to herpes simplex will be negative to B virus in the neutralization test. However, a sufficient number of sera will be negative to simplex, but positive to B virus, indicating that the assumed one-way cross is invalid. Also, if antibody to simplex is present, and this antibody is present in most adult macaques, then differentiation requires testing with B virus. At least 50% of these positive sera may appear to be negative for B virus if only tested with H. hominis. Approximately 25% of the remaining positive sera will have higher titers to B virus than to herpes simplex and 25% will have the same titers to both viruses. Further, complement is required by many of the test sera to detect the presence of antibodies to B virus."}
{"id": "PMID:223912", "title": "Stabilizing effect of magnesium chloride and sucrose on Sabin live polio vaccine.", "content": "A trivalent vaccine was stabilized with (a) 70% sucrose, (b) MgCl2 1M, and (c) 35% sucrose plus MgCl2 1/2M. A portion of each batch was kept at +4 degrees C and 22-25 degrees C. No change in titre for all 3 preparations was recorded after 9 weeks storage at +4 degrees C. While the potency of vaccines containing MgCl2 alone or mixed with sucrose and kept at +25-28 degrees C for 5 weeks was not altered, the vaccine containing only sucrose was less stable, and a drop of titre was noticed after 2 weeks of storage at +22-25 degrees C. Monovalent polio vaccines were also stabilized as above and kept at +4 degrees C or at -20 degrees C. It was found that regardless of the type of stabilizer used, 82 to 97 per cent of potency was retained after 9 months of storage at +4 degrees C or at -20 degrees C.", "contents": "Stabilizing effect of magnesium chloride and sucrose on Sabin live polio vaccine. A trivalent vaccine was stabilized with (a) 70% sucrose, (b) MgCl2 1M, and (c) 35% sucrose plus MgCl2 1/2M. A portion of each batch was kept at +4 degrees C and 22-25 degrees C. No change in titre for all 3 preparations was recorded after 9 weeks storage at +4 degrees C. While the potency of vaccines containing MgCl2 alone or mixed with sucrose and kept at +25-28 degrees C for 5 weeks was not altered, the vaccine containing only sucrose was less stable, and a drop of titre was noticed after 2 weeks of storage at +22-25 degrees C. Monovalent polio vaccines were also stabilized as above and kept at +4 degrees C or at -20 degrees C. It was found that regardless of the type of stabilizer used, 82 to 97 per cent of potency was retained after 9 months of storage at +4 degrees C or at -20 degrees C."}
{"id": "PMID:223913", "title": "Smallpox eradication: progress and problems.", "content": "In 1958, the Eleventh World Health Assembly, on the proposal of the USSR, approved a resolution for world-wide smallpox eradication. In that year alone the disease occurred in 59 countries, and in addition many other areas experienced imported cases. When the intensified eradication programme began in 1967, there were 33 countries with endemic smallpox and two more countries subsequently became endemic. These 33 countries had a population of over 1,200,000,000 and were located in four of the six WHO regions. The most important endemic area was in Asia, but the disease was also endemic in South America and in Africa, south of the Sahara. The intensified campaign quickly narrowed the endemic area. In April 1971, the last case was reported from Brazil, the stronghold of the disease in the Western Hemisphere. By 1973, with the exception of those in the Horn of Africa, smallpox transmission was interrupted in all African countries. The last case in Asia occurred in Bangladesh where variola major made its last stand. The last known case of smallpox in the world was reported from Somalia on 27 October 1977. If no more cases are discovered it will be possible, in two years from that date, to certify that smallpox has been eradicated from all areas of the world, and Member States of the World Health Organization will be able to celebrate an unprecedented victory for preventive medicine. The complete eradication of smallpox is not only the liberation of the world from one of its most dangerous diseases, but also provides an example of what can be achieved when countries throughout the world join together with a common aim.", "contents": "Smallpox eradication: progress and problems. In 1958, the Eleventh World Health Assembly, on the proposal of the USSR, approved a resolution for world-wide smallpox eradication. In that year alone the disease occurred in 59 countries, and in addition many other areas experienced imported cases. When the intensified eradication programme began in 1967, there were 33 countries with endemic smallpox and two more countries subsequently became endemic. These 33 countries had a population of over 1,200,000,000 and were located in four of the six WHO regions. The most important endemic area was in Asia, but the disease was also endemic in South America and in Africa, south of the Sahara. The intensified campaign quickly narrowed the endemic area. In April 1971, the last case was reported from Brazil, the stronghold of the disease in the Western Hemisphere. By 1973, with the exception of those in the Horn of Africa, smallpox transmission was interrupted in all African countries. The last case in Asia occurred in Bangladesh where variola major made its last stand. The last known case of smallpox in the world was reported from Somalia on 27 October 1977. If no more cases are discovered it will be possible, in two years from that date, to certify that smallpox has been eradicated from all areas of the world, and Member States of the World Health Organization will be able to celebrate an unprecedented victory for preventive medicine. The complete eradication of smallpox is not only the liberation of the world from one of its most dangerous diseases, but also provides an example of what can be achieved when countries throughout the world join together with a common aim."}
{"id": "PMID:223914", "title": "[A broad program of vaccination in the Ivory Coast].", "content": "This paper is a description of a vaccination programme against the most frequent communicable diseases among children: measles, tuberculosis, diphtheria, tetanus, whooping-cough and poliomyelitis. The programme is to be carried out in three different climate zones (town, forest and savanna) and over a period of six years. The project is supported by US-AID and UNICEF.", "contents": "[A broad program of vaccination in the Ivory Coast]. This paper is a description of a vaccination programme against the most frequent communicable diseases among children: measles, tuberculosis, diphtheria, tetanus, whooping-cough and poliomyelitis. The programme is to be carried out in three different climate zones (town, forest and savanna) and over a period of six years. The project is supported by US-AID and UNICEF."}
{"id": "PMID:223916", "title": "Monolayer culture of animal cells with the gyrogen equipped with tubes.", "content": "The gyrogen with tubes has been the object of repeated trials carried out over a period of some years. The aim of these trials was essentially to multiply BHK cells in monolayer and to reproduce the FMD virus in one operation. At the laboratory stage, the gyrogen consisted of 3 rolling flasks; at the pilot stage, it equalled 100 rolling flasks; and at the industrial stage which will be tested in the coming months, it should equal 500 flasks. The culture of cells on a glass support was not in itself new; the difficulty appeared when replicating the virus in order to obtain the high parameters necessary for the production of vaccine. Everything was done so that finally cell culture and viral multiplication could be carried out in situ in the same apparatus.", "contents": "Monolayer culture of animal cells with the gyrogen equipped with tubes. The gyrogen with tubes has been the object of repeated trials carried out over a period of some years. The aim of these trials was essentially to multiply BHK cells in monolayer and to reproduce the FMD virus in one operation. At the laboratory stage, the gyrogen consisted of 3 rolling flasks; at the pilot stage, it equalled 100 rolling flasks; and at the industrial stage which will be tested in the coming months, it should equal 500 flasks. The culture of cells on a glass support was not in itself new; the difficulty appeared when replicating the virus in order to obtain the high parameters necessary for the production of vaccine. Everything was done so that finally cell culture and viral multiplication could be carried out in situ in the same apparatus."}
{"id": "PMID:223917", "title": "Cell culture on beads used for the industrial production of foot-and-mouth disease virus.", "content": "The microcarrier culture technique has been applied to a pig kidney cell line. Microcarriers consisted of DEAE Sephadex A 50 beads washed and containing carboxymethyl cellulose. Sifted beads gave better results than unclassified material. Cells for inoculum were prepared in Roux flasks. The two types of fermentors which were used (operating capacity 100 l and 150 l) gave similar results. The growth of the cells can easily be followed by microscopic observation and cell count. The yields of cells per volume of spent medium were three times higher on microcarrier than in Roux bottles; the average doubling time was not modified. Foot-and-mouth disease virus can be produced with cells grown on beads. Vaccines prepared with these viruses induced good protection for pigs.", "contents": "Cell culture on beads used for the industrial production of foot-and-mouth disease virus. The microcarrier culture technique has been applied to a pig kidney cell line. Microcarriers consisted of DEAE Sephadex A 50 beads washed and containing carboxymethyl cellulose. Sifted beads gave better results than unclassified material. Cells for inoculum were prepared in Roux flasks. The two types of fermentors which were used (operating capacity 100 l and 150 l) gave similar results. The growth of the cells can easily be followed by microscopic observation and cell count. The yields of cells per volume of spent medium were three times higher on microcarrier than in Roux bottles; the average doubling time was not modified. Foot-and-mouth disease virus can be produced with cells grown on beads. Vaccines prepared with these viruses induced good protection for pigs."}
{"id": "PMID:223918", "title": "Multiplication of normal and virus-infected diploid cells cultivated on microcarriers.", "content": "In prelminary studies, growth of diploid cells (fetal calf buccal cells and chick embryo fibroblasts on dextran microcarriers was studied and compared to growth in monolayer. Growth coefficients obtained were always greater (by 2 fold) when microcarriers were used. Moreover, this technique had the advantage of reducing the number of manipulations and hence the risk of contamination. In two series of experiments, buccal epithelial cells were infected with vescicular stomatitis virus. Good virus multiplication was obtained.", "contents": "Multiplication of normal and virus-infected diploid cells cultivated on microcarriers. In prelminary studies, growth of diploid cells (fetal calf buccal cells and chick embryo fibroblasts on dextran microcarriers was studied and compared to growth in monolayer. Growth coefficients obtained were always greater (by 2 fold) when microcarriers were used. Moreover, this technique had the advantage of reducing the number of manipulations and hence the risk of contamination. In two series of experiments, buccal epithelial cells were infected with vescicular stomatitis virus. Good virus multiplication was obtained."}
{"id": "PMID:223919", "title": "Alterations of membrane glycoproteins in malignant cells.", "content": "Comparisons have been made of the carbohydrates bound to membrane proteins of control and malignant cells in culture. It has been found that most individual glycoproteins of control and malignant cells differ in their carbohydrate components. Differences between control and malignant cells have been foundin the glycoproteins of the various membrane systems (surface, nucleus, mitochondria, endoplasmic reticulum). It is suggested that the extensive changes in bound carbohydrates of the malignant cell permit the cell to live and divide but isolate the cell functionally. The extensive structural changes may also be responsible for the cascading of involvement of various processes within the malignant cell.", "contents": "Alterations of membrane glycoproteins in malignant cells. Comparisons have been made of the carbohydrates bound to membrane proteins of control and malignant cells in culture. It has been found that most individual glycoproteins of control and malignant cells differ in their carbohydrate components. Differences between control and malignant cells have been foundin the glycoproteins of the various membrane systems (surface, nucleus, mitochondria, endoplasmic reticulum). It is suggested that the extensive changes in bound carbohydrates of the malignant cell permit the cell to live and divide but isolate the cell functionally. The extensive structural changes may also be responsible for the cascading of involvement of various processes within the malignant cell."}
{"id": "PMID:223921", "title": "A human neoplastic hematopoietic cell line producing a fibroblast type of interferon.", "content": "1301 is a subline of the EBV-genome negative T leukemia line CCRF-CEM. IF was induced by Sendai virus. By use of neutralizing antisera and by studies of some physical properties it could be shown that IF was of the fibroblast type. This was confirmed by its antiviral effect on heterologous cell lines.", "contents": "A human neoplastic hematopoietic cell line producing a fibroblast type of interferon. 1301 is a subline of the EBV-genome negative T leukemia line CCRF-CEM. IF was induced by Sendai virus. By use of neutralizing antisera and by studies of some physical properties it could be shown that IF was of the fibroblast type. This was confirmed by its antiviral effect on heterologous cell lines."}
{"id": "PMID:223922", "title": "The use of frozen BHK21 C13 cells to control the biological parameters for cell and foot-and-mouth disease virus growth.", "content": "In order to control the four primary variables (cells, serum, medium and physical conditions) in a cell or virus growth system it is important to have a reliable and constant positive control with which to compare any variable of the system components. The use of aliquots of a frozen cell population (stored at -136 degrees C) for this purpose is the subject of this paper. Using such cells, tests have been established for the control of sera, media, cell susceptibility and the quality of serum treated DEAE Sephadex A50 beads.", "contents": "The use of frozen BHK21 C13 cells to control the biological parameters for cell and foot-and-mouth disease virus growth. In order to control the four primary variables (cells, serum, medium and physical conditions) in a cell or virus growth system it is important to have a reliable and constant positive control with which to compare any variable of the system components. The use of aliquots of a frozen cell population (stored at -136 degrees C) for this purpose is the subject of this paper. Using such cells, tests have been established for the control of sera, media, cell susceptibility and the quality of serum treated DEAE Sephadex A50 beads."}
{"id": "PMID:223923", "title": "Large-scale concentration and purification of virus suspension from microcarrier culture for the preparation of inactivated virus vaccines.", "content": "Because of the presence of bovine serum proteins in poliovirus and rabiesvirus suspensions harvested from microcarrier cultures, a concentration and purification process has been developed in order to remove these proteins. The process comprises clarification by filtration, concentration by ultrafiltration, gel filtration on Sepharose 6B and column chromatography on DEAE-Sephadex A50. The serum protein content of the virus suspensions if reduced to a serum dilution of less than 1: 10(6) at a virus antigen recovery rate of 70 to 80%.", "contents": "Large-scale concentration and purification of virus suspension from microcarrier culture for the preparation of inactivated virus vaccines. Because of the presence of bovine serum proteins in poliovirus and rabiesvirus suspensions harvested from microcarrier cultures, a concentration and purification process has been developed in order to remove these proteins. The process comprises clarification by filtration, concentration by ultrafiltration, gel filtration on Sepharose 6B and column chromatography on DEAE-Sephadex A50. The serum protein content of the virus suspensions if reduced to a serum dilution of less than 1: 10(6) at a virus antigen recovery rate of 70 to 80%."}
{"id": "PMID:223924", "title": "Some aspects of FMDV-production in growing cells and a closed system for concentration of FMDV by polyethylene glycol.", "content": "Different commercially available peptone preparations, all derived by enzymatic digestion of meat, were tested for their ability to replace the individual amino acids and polyethylene glycol (PEG)-treated serum in BHK suspended cell culture growth medium. Cell growth was not impaired if the individual amino acids were replaced by 3 g/l of peptone in combination with 3 g/l LAH and 5% PEG-treated bovine serum. The concentration of the latter could be reduced to 1% by gradually lowering the concentration in successive cell passages. No significant differences in growth stimulating properties were observed between the peptone preparations. The virus produced was concentrated and partly purified by precipitation with PEG, collection of the precipitate by filter-aid filtration and direct elution from filter cake in the filter by pumping one tenth the original volume of buffer through the filter. The whole procedure was performed in a simple closed system, offering maximum guarantee of bacteriological sterility and preventing virus aerosol formation in the surroundings.", "contents": "Some aspects of FMDV-production in growing cells and a closed system for concentration of FMDV by polyethylene glycol. Different commercially available peptone preparations, all derived by enzymatic digestion of meat, were tested for their ability to replace the individual amino acids and polyethylene glycol (PEG)-treated serum in BHK suspended cell culture growth medium. Cell growth was not impaired if the individual amino acids were replaced by 3 g/l of peptone in combination with 3 g/l LAH and 5% PEG-treated bovine serum. The concentration of the latter could be reduced to 1% by gradually lowering the concentration in successive cell passages. No significant differences in growth stimulating properties were observed between the peptone preparations. The virus produced was concentrated and partly purified by precipitation with PEG, collection of the precipitate by filter-aid filtration and direct elution from filter cake in the filter by pumping one tenth the original volume of buffer through the filter. The whole procedure was performed in a simple closed system, offering maximum guarantee of bacteriological sterility and preventing virus aerosol formation in the surroundings."}
{"id": "PMID:223925", "title": "Purification of poliovirus obtained from human diploid cells by means of DEAE-Sepharose.", "content": "Mahoney, MEF and Saukett poliovirus strains were grown on human diploid cells (MRC 5) and concentrated on Amicon filter. Concentrated viral suspensions containing 3H-uridine labelled virus were mixed with 14C-amino acid labelled cell extracts containing calf serum and passed through a DEAE-Sepharose column. Fractions eluted at various ionic strengths were analyzed for infectivity, radio-activity and serum content by counter immunoelectrophoresis in the presence of a rabbit anti-calf serum. A peak containing 40--60% of the input infectivity was easily obtained by elution with 0.01 M phosphate buffer at pH 7. The virus peak did not contain 14C or calf serum and its purity was controlled by PAGE-SDS electrophoresis and electron microscopy. This technique may be useful in the large-scale purification of viruses used in the preparation of inactivated vaccines.", "contents": "Purification of poliovirus obtained from human diploid cells by means of DEAE-Sepharose. Mahoney, MEF and Saukett poliovirus strains were grown on human diploid cells (MRC 5) and concentrated on Amicon filter. Concentrated viral suspensions containing 3H-uridine labelled virus were mixed with 14C-amino acid labelled cell extracts containing calf serum and passed through a DEAE-Sepharose column. Fractions eluted at various ionic strengths were analyzed for infectivity, radio-activity and serum content by counter immunoelectrophoresis in the presence of a rabbit anti-calf serum. A peak containing 40--60% of the input infectivity was easily obtained by elution with 0.01 M phosphate buffer at pH 7. The virus peak did not contain 14C or calf serum and its purity was controlled by PAGE-SDS electrophoresis and electron microscopy. This technique may be useful in the large-scale purification of viruses used in the preparation of inactivated vaccines."}
{"id": "PMID:223926", "title": "Construction of hybrid viruses in vitro and their possible use for the production of specific viral or cellular proteins.", "content": "The use of plasmid and bacteriophage vectors for cloning of DNA segments from procaryotes and eucaryotes is described. A similar approach is being developed with DNA viruses like simian virus 40 or adenovirus 2. Such hybrid viruses may permit the amplification of specific genes and the overproduction of the corresponding proteins.", "contents": "Construction of hybrid viruses in vitro and their possible use for the production of specific viral or cellular proteins. The use of plasmid and bacteriophage vectors for cloning of DNA segments from procaryotes and eucaryotes is described. A similar approach is being developed with DNA viruses like simian virus 40 or adenovirus 2. Such hybrid viruses may permit the amplification of specific genes and the overproduction of the corresponding proteins."}
{"id": "PMID:223932", "title": "[The surgical treatment of Klippel-Trenaunay syndrome (author's transl)].", "content": "Three cases of congenital angiodysplasies of the extremities, classified as Klippel-Trenaunay syndrome, underwent to surgical treatment. These cases, clinically similar, have shown a quite different pathogenesis, according to which the surgical treatment has been modified. Once again we recommend a complete diagnostic study every time one find varicosities of the extremities which are atipical for time of appearance, territories involved or for aspect and thus be congenital varicosities with complex pathogenesis.", "contents": "[The surgical treatment of Klippel-Trenaunay syndrome (author's transl)]. Three cases of congenital angiodysplasies of the extremities, classified as Klippel-Trenaunay syndrome, underwent to surgical treatment. These cases, clinically similar, have shown a quite different pathogenesis, according to which the surgical treatment has been modified. Once again we recommend a complete diagnostic study every time one find varicosities of the extremities which are atipical for time of appearance, territories involved or for aspect and thus be congenital varicosities with complex pathogenesis."}
{"id": "PMID:223933", "title": "Virus particles in normal prostate tissues of mice from ten strains, with special reference to type-B virus particles.", "content": "Prostate tissues of a total of 61 normal mice from 10 different strains, including high (C3H/Dm, RIII/Dm, and A/Dm) and low (BALB/c/Dm, C3Hf/Bi/Dm, and C3Hf/He/TEX) mammary cancer, and high (AKR/Dm) and low (CBA/J/Cr, SJL/J/Cr, and C57/BL/6/TEX) leukemia strains were examined by electron microscopy for the presence of virus particles. These studies demonstrated that type-B virus particles were present in normal prostate tissues of some old mice from all the three high (C3H/Dm, RIII/Dm, and A/Dm) and one low (BALB/c/Dm) mammary cancer strains. They further demonstrated that varying number of type-C virus particles were present in prostate tissues of some young and old mice, including those from all the 10 strains, especially in a larger number in older mice, and that intracisternal type-A virus particles were observed in all the mice examined. Immunological characterization of type-B virus particles by fixed immunofluorescence tests and immunoelectron microscopy revealed that type-B virus particles in normal prostate tissues of old C3H/Dm and A/Dm mice are morphologically and immunologically similar to the mouse mammary tumor virus. Thus, prostate tissues of mice can be a potential source of horizontally transmitted mammary tumor virus in mice of at least some high mammary cancer strains.", "contents": "Virus particles in normal prostate tissues of mice from ten strains, with special reference to type-B virus particles. Prostate tissues of a total of 61 normal mice from 10 different strains, including high (C3H/Dm, RIII/Dm, and A/Dm) and low (BALB/c/Dm, C3Hf/Bi/Dm, and C3Hf/He/TEX) mammary cancer, and high (AKR/Dm) and low (CBA/J/Cr, SJL/J/Cr, and C57/BL/6/TEX) leukemia strains were examined by electron microscopy for the presence of virus particles. These studies demonstrated that type-B virus particles were present in normal prostate tissues of some old mice from all the three high (C3H/Dm, RIII/Dm, and A/Dm) and one low (BALB/c/Dm) mammary cancer strains. They further demonstrated that varying number of type-C virus particles were present in prostate tissues of some young and old mice, including those from all the 10 strains, especially in a larger number in older mice, and that intracisternal type-A virus particles were observed in all the mice examined. Immunological characterization of type-B virus particles by fixed immunofluorescence tests and immunoelectron microscopy revealed that type-B virus particles in normal prostate tissues of old C3H/Dm and A/Dm mice are morphologically and immunologically similar to the mouse mammary tumor virus. Thus, prostate tissues of mice can be a potential source of horizontally transmitted mammary tumor virus in mice of at least some high mammary cancer strains."}
{"id": "PMID:223934", "title": "Fusion of XC cells by murine type-C viruses: cinematographic observations.", "content": "Continuous observations on the processes of multikaryon formation by purified murine type-C virus, produced by a line of murine myeloma cell cultures and Rauscher leukemia virus, were carried out by cinematography. The process first began by fusion of two mononucleated cells and additional cells continued to introduce their cytoplasm and nucleus one after another to give rise to multinucleated giant cells. These findings strongly suggested that the formation of multikaryons is due to a cellular fusion process and not to endomitosis.", "contents": "Fusion of XC cells by murine type-C viruses: cinematographic observations. Continuous observations on the processes of multikaryon formation by purified murine type-C virus, produced by a line of murine myeloma cell cultures and Rauscher leukemia virus, were carried out by cinematography. The process first began by fusion of two mononucleated cells and additional cells continued to introduce their cytoplasm and nucleus one after another to give rise to multinucleated giant cells. These findings strongly suggested that the formation of multikaryons is due to a cellular fusion process and not to endomitosis."}
{"id": "PMID:223935", "title": "Establishment of cell lines from the wild rodent Millardia meltada and tests for endogenous virus.", "content": "Four cell lines were established from the wild rodent, Millardia meltada; an untransformed cell line (MM-D), a non-producer (NP) cell line transformed with murine sarcoma virus (MM-CL4), and SV40-transformed cell lines (MM-8 MM-663). MM-D is epithelioid and contact-inhibited, whereas MM-CL4, MM-8, and MM-663 are fibroblastic and grow piling up. No endogenous virus was induced in Millardia cell lines by a long-term culture with various inducers. Millardia cell DNA has no nucleotide sequence homology with cDNA of either murine leukemia virus or rat endogenous virus.", "contents": "Establishment of cell lines from the wild rodent Millardia meltada and tests for endogenous virus. Four cell lines were established from the wild rodent, Millardia meltada; an untransformed cell line (MM-D), a non-producer (NP) cell line transformed with murine sarcoma virus (MM-CL4), and SV40-transformed cell lines (MM-8 MM-663). MM-D is epithelioid and contact-inhibited, whereas MM-CL4, MM-8, and MM-663 are fibroblastic and grow piling up. No endogenous virus was induced in Millardia cell lines by a long-term culture with various inducers. Millardia cell DNA has no nucleotide sequence homology with cDNA of either murine leukemia virus or rat endogenous virus."}
{"id": "PMID:223938", "title": "Immunofluorescence studies for hepatitis A virus and hepatitis B surface and core antigen in liver biopsies from patients with acute viral hepatitis.", "content": "Immunofluorescence studies for hepatitis A virus and hepatitis B surface and core antigen were performed on liver biopsies from 48 patients with acute viral hepatitis. Hepatitis A virus was detected in 11 out of 17 patients with type A hepatitis and was not found in patients with type B or non-A non-B hepatitis. Hepatitis B surface and core antigens were detected in 2, hepatitis B core antigen alone in 1, and hepatitis B surface antigen alone in 4 out of 24 patients with type B hepatitis. Neither hepatitis B surface nor core antigen were found in patients with type A or non-A non-B hepatitis. One patient with both type A and B hepatitis were all negative for hepatitis A virus, and hepatitis B surface and core antigens. Immunofluorescence examination for hepatitis A virus in human liver biopsies appears to be a sensitive and specific technique and might be valuable in the search for possible chronic carriers of hepatitis A virus.", "contents": "Immunofluorescence studies for hepatitis A virus and hepatitis B surface and core antigen in liver biopsies from patients with acute viral hepatitis. Immunofluorescence studies for hepatitis A virus and hepatitis B surface and core antigen were performed on liver biopsies from 48 patients with acute viral hepatitis. Hepatitis A virus was detected in 11 out of 17 patients with type A hepatitis and was not found in patients with type B or non-A non-B hepatitis. Hepatitis B surface and core antigens were detected in 2, hepatitis B core antigen alone in 1, and hepatitis B surface antigen alone in 4 out of 24 patients with type B hepatitis. Neither hepatitis B surface nor core antigen were found in patients with type A or non-A non-B hepatitis. One patient with both type A and B hepatitis were all negative for hepatitis A virus, and hepatitis B surface and core antigens. Immunofluorescence examination for hepatitis A virus in human liver biopsies appears to be a sensitive and specific technique and might be valuable in the search for possible chronic carriers of hepatitis A virus."}
{"id": "PMID:223941", "title": "Phosphomonoesterases in the male genital system of some mammals.", "content": "The various male genital organs of the experimental animals used in this investigation (rat, guinea pig, rabbit, cat and dog) showed a widely different localizations of alkaline and acid phosphatases. Alkaline phosphatase was presented as secretory, stromal, nuclear and vascular, while with acid phosphatase, distinction was made only between secretory and nuclear phosphatases. Although the morphological distributions of both enzymes were sometimes overlapping, they were not identical.", "contents": "Phosphomonoesterases in the male genital system of some mammals. The various male genital organs of the experimental animals used in this investigation (rat, guinea pig, rabbit, cat and dog) showed a widely different localizations of alkaline and acid phosphatases. Alkaline phosphatase was presented as secretory, stromal, nuclear and vascular, while with acid phosphatase, distinction was made only between secretory and nuclear phosphatases. Although the morphological distributions of both enzymes were sometimes overlapping, they were not identical."}
{"id": "PMID:223947", "title": "Plasma prednisolone levels and adrenocortical responsiveness after administration of prednisolone-21-phosphate as a retention enema.", "content": "Plasma prednisolone levels have been measured by radioimmunoassay after oral and rectal administration to healthy volunteers and to patients with idiopathic proctocolitis. The amount of prednisolone absorbed from a 20 mg retention enema given to patients with proctocolitis was about 44% of that absorbed from the same dose orally administered. Adrenocortical response to synthetic ACTH in patients receiving prolonged rectal therapy was either normal, or only slightly impaired, and this may be related to the pattern of steroid absorption rather than to the total amount absorbed.", "contents": "Plasma prednisolone levels and adrenocortical responsiveness after administration of prednisolone-21-phosphate as a retention enema. Plasma prednisolone levels have been measured by radioimmunoassay after oral and rectal administration to healthy volunteers and to patients with idiopathic proctocolitis. The amount of prednisolone absorbed from a 20 mg retention enema given to patients with proctocolitis was about 44% of that absorbed from the same dose orally administered. Adrenocortical response to synthetic ACTH in patients receiving prolonged rectal therapy was either normal, or only slightly impaired, and this may be related to the pattern of steroid absorption rather than to the total amount absorbed."}
{"id": "PMID:223948", "title": "Effect of ouabain on Na,K-ATPase and electrolyte transport in the dog ileum in vivo.", "content": "It is currently believed that the rate and direction of sodium transport in the small intestine may be regulated by the activity of Na,K-ATPase in the basolateral cell membrane. We tested this hypothesis by selectively infusing ouabain, a known inhibitor of Na,K-ATPase, into the mesenteric artery supplying a perfused loop of ileum in 18 dogs. Before ouabain infusion there were significant correlations between the activity of Na,K-ATPase and net and lumen to plasma fluxes of sodium and chloride. After ouabain, there was no significant change in sodium and chloride transport, unidirectional fluxes or transmucosal potential difference, despite a 50% reduction in Na,K-ATPase activity. Furthermore, there was no significant correlation between Na,K-ATPase activity and sodium or chloride transport after ouabain. The only statistically significant effect of ouabain infusion was a reduction in the rate of bicarbonate secretion. Thus, the results of our experiments suggest that mucosal Na,K-ATPase is not a rate-limiting step in the absorption of sodium and chloride in the dog ileum, though it may be an important facilitative factor.", "contents": "Effect of ouabain on Na,K-ATPase and electrolyte transport in the dog ileum in vivo. It is currently believed that the rate and direction of sodium transport in the small intestine may be regulated by the activity of Na,K-ATPase in the basolateral cell membrane. We tested this hypothesis by selectively infusing ouabain, a known inhibitor of Na,K-ATPase, into the mesenteric artery supplying a perfused loop of ileum in 18 dogs. Before ouabain infusion there were significant correlations between the activity of Na,K-ATPase and net and lumen to plasma fluxes of sodium and chloride. After ouabain, there was no significant change in sodium and chloride transport, unidirectional fluxes or transmucosal potential difference, despite a 50% reduction in Na,K-ATPase activity. Furthermore, there was no significant correlation between Na,K-ATPase activity and sodium or chloride transport after ouabain. The only statistically significant effect of ouabain infusion was a reduction in the rate of bicarbonate secretion. Thus, the results of our experiments suggest that mucosal Na,K-ATPase is not a rate-limiting step in the absorption of sodium and chloride in the dog ileum, though it may be an important facilitative factor."}
{"id": "PMID:223949", "title": "Turcot's syndrome and its mode of inheritance.", "content": "Two sisters with Turcot's syndrome, in which malignant cerebral neoplasms are associated with colonic polyposis, are presented. Cases reported in the literature, including some familial cases, have also been analysed. In familial cases, sex was unrelated to the occurrence of this disease and it was found only among siblings of the same parents and not in other members of the family. There was consanguinity in the parents of the patients in two out of three families. We therefore concluded that the mode of inheritance in this condition is autosomal recessive and that it is genetically distinct from the ordinary form of familial polyposis coli. Support is lent to the absence of an association between the two disorders by a difference in the number, size, and distribution of the colonic polyps found in Turcot's syndrome as compared with familial polyposis coli.", "contents": "Turcot's syndrome and its mode of inheritance. Two sisters with Turcot's syndrome, in which malignant cerebral neoplasms are associated with colonic polyposis, are presented. Cases reported in the literature, including some familial cases, have also been analysed. In familial cases, sex was unrelated to the occurrence of this disease and it was found only among siblings of the same parents and not in other members of the family. There was consanguinity in the parents of the patients in two out of three families. We therefore concluded that the mode of inheritance in this condition is autosomal recessive and that it is genetically distinct from the ordinary form of familial polyposis coli. Support is lent to the absence of an association between the two disorders by a difference in the number, size, and distribution of the colonic polyps found in Turcot's syndrome as compared with familial polyposis coli."}
{"id": "PMID:223950", "title": "Cyclic AMP and cyclic GMP levels in human colonic mucosa before and during chenodeoxycholic acid therapy.", "content": "Previous experimental studies suggest that bile salt-induced colonic fluid secretion is mediated by adenosine 3':5'-phosphate (cyclic AMP). Two biopsy specimens of colonic mucosa were obtained endoscopically before and after different periods of therapy (five, 10, or 15 days), from each of 21 patients receiving chenodeoxycholic acid. A rise of cyclic AMP intracellular levels was found, but only after five and 10 days of treatment was the increase statistically significant when compared with basal levels. Similar changes were observed for guanosine 3':5'-phosphate (cyclic GMP), but percentage increases were higher than for cyclic AMP. Initial diarrhoea disappeared spontaneously, and at 15 days the levels of both cyclic nucleotides were not significantly different from basal levels. Our findings suggest that colonic adaptation to increase in luminal bile salt levels is related to changes in intracellular levels of cyclic nucleotides and support the hypothesis that not only cyclic AMP, but also cyclic GMP may play an important role in producing bile salt-induced diarrhoea in man.", "contents": "Cyclic AMP and cyclic GMP levels in human colonic mucosa before and during chenodeoxycholic acid therapy. Previous experimental studies suggest that bile salt-induced colonic fluid secretion is mediated by adenosine 3':5'-phosphate (cyclic AMP). Two biopsy specimens of colonic mucosa were obtained endoscopically before and after different periods of therapy (five, 10, or 15 days), from each of 21 patients receiving chenodeoxycholic acid. A rise of cyclic AMP intracellular levels was found, but only after five and 10 days of treatment was the increase statistically significant when compared with basal levels. Similar changes were observed for guanosine 3':5'-phosphate (cyclic GMP), but percentage increases were higher than for cyclic AMP. Initial diarrhoea disappeared spontaneously, and at 15 days the levels of both cyclic nucleotides were not significantly different from basal levels. Our findings suggest that colonic adaptation to increase in luminal bile salt levels is related to changes in intracellular levels of cyclic nucleotides and support the hypothesis that not only cyclic AMP, but also cyclic GMP may play an important role in producing bile salt-induced diarrhoea in man."}
{"id": "PMID:223954", "title": "Relaxin and collagen metabolism.", "content": "The influence of the peptide hormone relaxin on collagen metabolism was studied in the symphysis pubis of the mouse. In the tissue the content of water and of acid soluble collagen in relation to total collagen is increased by hormonal treatment. Total collagen calculated in relation to the dry weight is decreased. Collagenase which was also detected in the symphyses of the controls is slightly enhanced. In serum collagen peptidase and collagen peptidase inhibitor as well as cyclic AMP exhibit distinctly increased levels. The effects can be suppressed by administration of relaxin-specific antisera. The data make clear that in the symphysis relaxin activates the collagenolytic system.", "contents": "Relaxin and collagen metabolism. The influence of the peptide hormone relaxin on collagen metabolism was studied in the symphysis pubis of the mouse. In the tissue the content of water and of acid soluble collagen in relation to total collagen is increased by hormonal treatment. Total collagen calculated in relation to the dry weight is decreased. Collagenase which was also detected in the symphyses of the controls is slightly enhanced. In serum collagen peptidase and collagen peptidase inhibitor as well as cyclic AMP exhibit distinctly increased levels. The effects can be suppressed by administration of relaxin-specific antisera. The data make clear that in the symphysis relaxin activates the collagenolytic system."}
{"id": "PMID:223955", "title": "Surface localization of apolipoprotein AII in lipoprotein-complexes.", "content": "Lipoprotein particles reconstituted from the apolipoprotein AII (apo AII) component of human serum high density lipoprotein, phosphatidylcholine and lysophosphatidylcholine were covalently linked to the imidoester groups of a polystyrene residue. Apo AII was proteolytically digested with thermolysin after delipidation. The covalently bound peptides remaining at the resin were cleaved and separated by combined two-dimensional electrophoresis/chromatography. The peptides were isolated, hydrolyzed and their amino acid composition determined. They were assigned to the apo AII sequence. Since the imidoester groups on the surface of the resin carrier cannot react with buried lysine residues, this method gives strong chemical evidence for the spreading of the apo AII polypeptide chain over the surface of the lipoprotein particle, as far as the sequence carrying lysine residues between residue 22 and 55 of each symmetrical half is concerned.", "contents": "Surface localization of apolipoprotein AII in lipoprotein-complexes. Lipoprotein particles reconstituted from the apolipoprotein AII (apo AII) component of human serum high density lipoprotein, phosphatidylcholine and lysophosphatidylcholine were covalently linked to the imidoester groups of a polystyrene residue. Apo AII was proteolytically digested with thermolysin after delipidation. The covalently bound peptides remaining at the resin were cleaved and separated by combined two-dimensional electrophoresis/chromatography. The peptides were isolated, hydrolyzed and their amino acid composition determined. They were assigned to the apo AII sequence. Since the imidoester groups on the surface of the resin carrier cannot react with buried lysine residues, this method gives strong chemical evidence for the spreading of the apo AII polypeptide chain over the surface of the lipoprotein particle, as far as the sequence carrying lysine residues between residue 22 and 55 of each symmetrical half is concerned."}
{"id": "PMID:223956", "title": "Conformational analysis of serum apolipoprotein AII in lipoprotein complexes with bifunctional crosslinking reagents.", "content": "Apolipoprotein AII isolated from human serum high density lipoproteins was recombined with phosphatidylcholine to yield homogeneous particles of 80-120 A diameter. The radioactive bifunctional crosslinkers dimethyl [1,1'-14C]suberimidate and dimethyl 4,4'-dithiobis([1-14C]butyrimidate) were reacted with these particles. The kinetics of the reactions and the localisation of the crosslinked lysines of the polypeptide chains were determined. Thermolysin hydrolysis followed by two-dimensional separation of the peptides and isolation of the mono- and bifunctionally modified peptides allowed the assignment of the crosslinked peptides of the apoprotein AII seqeunce. The crosslinking pattern indicates a close-neighbour relationship (13-15 A) of the peptide chains between amino acid residues 3, 23, 46 and 55 of the symmetrical halves of the apo AII molecule. A reconstruction of the secondary structure of Apo AII in the lipoprotein complex on the basis of theoretical calculations is given and correlated with the chemical data.", "contents": "Conformational analysis of serum apolipoprotein AII in lipoprotein complexes with bifunctional crosslinking reagents. Apolipoprotein AII isolated from human serum high density lipoproteins was recombined with phosphatidylcholine to yield homogeneous particles of 80-120 A diameter. The radioactive bifunctional crosslinkers dimethyl [1,1'-14C]suberimidate and dimethyl 4,4'-dithiobis([1-14C]butyrimidate) were reacted with these particles. The kinetics of the reactions and the localisation of the crosslinked lysines of the polypeptide chains were determined. Thermolysin hydrolysis followed by two-dimensional separation of the peptides and isolation of the mono- and bifunctionally modified peptides allowed the assignment of the crosslinked peptides of the apoprotein AII seqeunce. The crosslinking pattern indicates a close-neighbour relationship (13-15 A) of the peptide chains between amino acid residues 3, 23, 46 and 55 of the symmetrical halves of the apo AII molecule. A reconstruction of the secondary structure of Apo AII in the lipoprotein complex on the basis of theoretical calculations is given and correlated with the chemical data."}
{"id": "PMID:223957", "title": "Hepatoblastoma with adenomatoid renal epithelium.", "content": "A case is described in which a hepatoblastoma is associated with a renal malformation where adenomatoid epithelium lines Bowman's capsule and the adjacent part of the proximal tubule. The significance of this is discussed in relation to the association of developmental malformations with neoplasia.", "contents": "Hepatoblastoma with adenomatoid renal epithelium. A case is described in which a hepatoblastoma is associated with a renal malformation where adenomatoid epithelium lines Bowman's capsule and the adjacent part of the proximal tubule. The significance of this is discussed in relation to the association of developmental malformations with neoplasia."}
{"id": "PMID:223959", "title": "Deinstitutionalization in the absence of consensus.", "content": "The process of deinstitutionalization began almost unnoticed in 1955 as state hospital populations started to decline, and it proceeded without adequate planning and without development of a social consensus. The inevitable result was strong criticism, severe personal dislocations, and, with rare exceptions, programmatic chaos. The authors trace and describe the reasons for the growing polarization about deinstitutionalization among such groups as mental health professionals, public officials, families, advocacy groups, citizens, and unions. They also note that between 1950 and 1970 the total institutionalized population in the U.S. was not reduced but simply shifted. Deinstitutionalization should focus not on the location of care but on the broader problem of improving the lot of persons with chronic illness, regardless of its cause or time of onset, the authors suggest. They outline the basic elements of a service and financing system to meet both the daily-living and the specifically medical needs of the chronically ill.", "contents": "Deinstitutionalization in the absence of consensus. The process of deinstitutionalization began almost unnoticed in 1955 as state hospital populations started to decline, and it proceeded without adequate planning and without development of a social consensus. The inevitable result was strong criticism, severe personal dislocations, and, with rare exceptions, programmatic chaos. The authors trace and describe the reasons for the growing polarization about deinstitutionalization among such groups as mental health professionals, public officials, families, advocacy groups, citizens, and unions. They also note that between 1950 and 1970 the total institutionalized population in the U.S. was not reduced but simply shifted. Deinstitutionalization should focus not on the location of care but on the broader problem of improving the lot of persons with chronic illness, regardless of its cause or time of onset, the authors suggest. They outline the basic elements of a service and financing system to meet both the daily-living and the specifically medical needs of the chronically ill."}
{"id": "PMID:223962", "title": "Does insulin dependent diabetes mellitus have a viral etiology?", "content": "Clinical, epidemiological, and experimental observations suggest that common viruses may play an etiologic role in at least some cases of insulin dependent diabetes mellitus. The evidence is summarized and critically assessed in this presentation.", "contents": "Does insulin dependent diabetes mellitus have a viral etiology? Clinical, epidemiological, and experimental observations suggest that common viruses may play an etiologic role in at least some cases of insulin dependent diabetes mellitus. The evidence is summarized and critically assessed in this presentation."}
{"id": "PMID:223963", "title": "Malignant soft tissue tumors (malignant fibrous histiocytoma, pleomorphic liposarcoma, and pleomorphic rhabdomyosarcoma): an electron microscopic study.", "content": "A comparative ultrastructural analysis of malignant soft tissue tumors (malignant fibrous histiocytoma, pleomorphic liposarcoma, and pleomorphic rhabdomyosarcoma) revealed similar ultrastructural features in this group of tumors. However, by electron microscopy these tumors can be differentiated on the basis of cytoplasmic and extracytoplasmic features (myosin filaments, lipid droplets, and perinuclear intermediate filaments, for example). This is even true of less well differentiated tumors and tumor cells. These findings support and amplify the concept of a common histogenesis for tumors of mesenchymal origin. Paradoxical features observed by light microscopy warrant further study by electron microscopy if the correct diagnosis is to be made in atypical cases, such as apparent malignant fibrous histiocytoma with cross striations.", "contents": "Malignant soft tissue tumors (malignant fibrous histiocytoma, pleomorphic liposarcoma, and pleomorphic rhabdomyosarcoma): an electron microscopic study. A comparative ultrastructural analysis of malignant soft tissue tumors (malignant fibrous histiocytoma, pleomorphic liposarcoma, and pleomorphic rhabdomyosarcoma) revealed similar ultrastructural features in this group of tumors. However, by electron microscopy these tumors can be differentiated on the basis of cytoplasmic and extracytoplasmic features (myosin filaments, lipid droplets, and perinuclear intermediate filaments, for example). This is even true of less well differentiated tumors and tumor cells. These findings support and amplify the concept of a common histogenesis for tumors of mesenchymal origin. Paradoxical features observed by light microscopy warrant further study by electron microscopy if the correct diagnosis is to be made in atypical cases, such as apparent malignant fibrous histiocytoma with cross striations."}
{"id": "PMID:223964", "title": "Does the Z gene variant of alpha-1-antitrypsin predispose to hepatic carcinoma?", "content": "In 10 of 56 patients with primary liver carcinoma the nontumorous hepatocytes contained diastase resistant, periodic acid-Schiff positive and alpha-1-antitrypsin positive (immunoperoxidase technique) globules. This is a frequency of 18 per cent among patients with liver carcinoma against 6 per cent in an unselected autopsy series. The tumors were of the hepatocellular or mixed type in nine of the 10 patients, and the frequency among such patients was 23 per cent. We consider that these globules indicate a carrier of the protease inhibitor allele of the Z gene variant (single or double).", "contents": "Does the Z gene variant of alpha-1-antitrypsin predispose to hepatic carcinoma? In 10 of 56 patients with primary liver carcinoma the nontumorous hepatocytes contained diastase resistant, periodic acid-Schiff positive and alpha-1-antitrypsin positive (immunoperoxidase technique) globules. This is a frequency of 18 per cent among patients with liver carcinoma against 6 per cent in an unselected autopsy series. The tumors were of the hepatocellular or mixed type in nine of the 10 patients, and the frequency among such patients was 23 per cent. We consider that these globules indicate a carrier of the protease inhibitor allele of the Z gene variant (single or double)."}
{"id": "PMID:223965", "title": "Budd-Chiari syndrome caused by undifferentiated small round cell tumor of the liver in an adult.", "content": "An undifferentiated small round cell tumor of the liver in a 60 year old black male is described. Although the light microscopic findings in this tumor were strongly suggestive of embryonal rhabdomyosarcoma, the ultrastructural study disclosed no myofibrils or other specific characteristics. Thus, we classify this tumor as an embryonic tumor or primitive mesenchymal tumor of the liver.", "contents": "Budd-Chiari syndrome caused by undifferentiated small round cell tumor of the liver in an adult. An undifferentiated small round cell tumor of the liver in a 60 year old black male is described. Although the light microscopic findings in this tumor were strongly suggestive of embryonal rhabdomyosarcoma, the ultrastructural study disclosed no myofibrils or other specific characteristics. Thus, we classify this tumor as an embryonic tumor or primitive mesenchymal tumor of the liver."}
{"id": "PMID:223966", "title": "Triplex gene dosage effect of TPI and G3PD in a human lymphoblastoid cell line with partial trisomy 12p13 and 18p.", "content": "The EBV-induced lymphoblastoid line established from a patient carrying a duplication of the distal part of chromosome 12 short arm (12p13) retained the original partial trisomy and displayed the same triplex gene dosage effect for TPI and G3PD as found in the patient's RBC and WBC.", "contents": "Triplex gene dosage effect of TPI and G3PD in a human lymphoblastoid cell line with partial trisomy 12p13 and 18p. The EBV-induced lymphoblastoid line established from a patient carrying a duplication of the distal part of chromosome 12 short arm (12p13) retained the original partial trisomy and displayed the same triplex gene dosage effect for TPI and G3PD as found in the patient's RBC and WBC."}
{"id": "PMID:223973", "title": "Poliovirus-induced suppression of lymphocyte stimulation: a macrophage-mediated effect.", "content": "Poliovirus was shown to suppress the in vitro response of human mononuclear blood cells stimulated with phytohaemagglutinin (PHA), pokeweed mitogen (PWM), tuberculin purified protein derivative (PPD) or allogeneic cells. The suppression required infectious virus and the presence of macrophages. Experiments with combined cultures of human lymphocytes stimulated with PHA, PWM, PPD or allogeneic cells, and different numbers of autologous macrophages indicated that both lymphocyte stimulation and the inhibitory effect of poliovirus increased with increasing ratio of macrophages to lymphocytes. The response of human lymphocytes to PHA also was enhanced when autologous macrophages were replaced with murine macrophages. Mouse hepatitis virus inhibited this enhancing effect whereas poliovirus failed to do so. The findings confirm our previous suggestion that poliovirus inhibits stimulation of lymphocytes by suppressing the enhancing effect of macrophages.", "contents": "Poliovirus-induced suppression of lymphocyte stimulation: a macrophage-mediated effect. Poliovirus was shown to suppress the in vitro response of human mononuclear blood cells stimulated with phytohaemagglutinin (PHA), pokeweed mitogen (PWM), tuberculin purified protein derivative (PPD) or allogeneic cells. The suppression required infectious virus and the presence of macrophages. Experiments with combined cultures of human lymphocytes stimulated with PHA, PWM, PPD or allogeneic cells, and different numbers of autologous macrophages indicated that both lymphocyte stimulation and the inhibitory effect of poliovirus increased with increasing ratio of macrophages to lymphocytes. The response of human lymphocytes to PHA also was enhanced when autologous macrophages were replaced with murine macrophages. Mouse hepatitis virus inhibited this enhancing effect whereas poliovirus failed to do so. The findings confirm our previous suggestion that poliovirus inhibits stimulation of lymphocytes by suppressing the enhancing effect of macrophages."}
{"id": "PMID:223974", "title": "The in vitro effects of propranolol and atenolol on neutrophil motility and post-phagocytic metabolic activity.", "content": "Propranolol at concentrations of 1 x 10(-6) to 1 x 10(-4) M consistently increased neutrophil motility as measured in Boyden chambers. The effects were not due solely to stimulation of random migration and chemokinesis but also of directional motility. Propranolol, over a similar concentration range, caused inhibition of post-phagocytic cell metabolic activity (hexose monophosphate shunt, nitro-blue tetrazolium reduction and protein iodination) without any detectable effect on the ingestion rate of Candida albicans. Atenolol had no effect on any of these neutrophil functions. Both drugs were without effect on glycolysis and intracellular cyclic AMP levels. Propranolol however, at concentrations which stimulated cell motility, caused increased intracellular cyclic GMP levels. It is suggested that propranolol may stimulate neutrophil motility by promoting increased intracellular cyclic GMP levels or by decreasing neutrophil superoxide production.", "contents": "The in vitro effects of propranolol and atenolol on neutrophil motility and post-phagocytic metabolic activity. Propranolol at concentrations of 1 x 10(-6) to 1 x 10(-4) M consistently increased neutrophil motility as measured in Boyden chambers. The effects were not due solely to stimulation of random migration and chemokinesis but also of directional motility. Propranolol, over a similar concentration range, caused inhibition of post-phagocytic cell metabolic activity (hexose monophosphate shunt, nitro-blue tetrazolium reduction and protein iodination) without any detectable effect on the ingestion rate of Candida albicans. Atenolol had no effect on any of these neutrophil functions. Both drugs were without effect on glycolysis and intracellular cyclic AMP levels. Propranolol however, at concentrations which stimulated cell motility, caused increased intracellular cyclic GMP levels. It is suggested that propranolol may stimulate neutrophil motility by promoting increased intracellular cyclic GMP levels or by decreasing neutrophil superoxide production."}
{"id": "PMID:223975", "title": "Induction of suppressor cells by sodium periodate: the opposite expression of periodate-induced lymphocyte activation in spleen cells of normal and nude mice.", "content": "Normal mouse spleen cells treated with sodium periodate for 10 min at 4 degrees are stimulated to undergo blastogenesis and to incorporate thymidine. In contrast, periodate treatment does not stimulate DNA synthesis in nude mice spleen cells. The effect of such treatment on the antibody response in vitro induced by sheep red blood cells (SRBC) and by trinitrophenyl polyacrylamide (TNP-PAA), a T-independent antigen has been evaluated. Periodic-induced proliferation is accompanied by a marked inhibition of the immune response to both of these antigens in normal mouse spleen cells. Mild oxidation of nude cells with periodate markedly enhances their anti-TNP response elicited by TNP-PAA. The data suggest that periodate-induced immune suppression is associated with T lymphocytes. Furthermore, periodate-treated cells are capable of suppressing the in vitro antibody response of untreated normal cells.", "contents": "Induction of suppressor cells by sodium periodate: the opposite expression of periodate-induced lymphocyte activation in spleen cells of normal and nude mice. Normal mouse spleen cells treated with sodium periodate for 10 min at 4 degrees are stimulated to undergo blastogenesis and to incorporate thymidine. In contrast, periodate treatment does not stimulate DNA synthesis in nude mice spleen cells. The effect of such treatment on the antibody response in vitro induced by sheep red blood cells (SRBC) and by trinitrophenyl polyacrylamide (TNP-PAA), a T-independent antigen has been evaluated. Periodic-induced proliferation is accompanied by a marked inhibition of the immune response to both of these antigens in normal mouse spleen cells. Mild oxidation of nude cells with periodate markedly enhances their anti-TNP response elicited by TNP-PAA. The data suggest that periodate-induced immune suppression is associated with T lymphocytes. Furthermore, periodate-treated cells are capable of suppressing the in vitro antibody response of untreated normal cells."}
{"id": "PMID:223976", "title": "Evidence for the role of superoxide radicals in neutrophil-mediated cytotoxicity.", "content": "Human peripheral neutrophils became cytotoxic to chicken red blood cells (CRBC) in the presence of lectins as assessed by release of 51chromium from labelled target cells. Phytohaemagglutinin (PHA) and concanavalin A (Con A), which caused time-dependent and dose-dependent cytotoxicity over a concentration range of 25--400 microgram/ml, also caused significant generation of superoxide radicals as measured by ferricytochrome C reduction. Pokeweed mitogen, which does not induce cytotoxicity over the same concentration range, was unable to promote superoxide generation by neutrophils. PHA-induced generation of superoxide paralleled and appeared to precede PHA-dependent cytotoxicity. Superoxide dismutase (SOD), which enzymatically destroys superoxide, caused moderate inhibition of PHA-dependent cytotoxicity over the concentration range of 100--500 microgram/ml whereas catalytically inactive enzyme had no effect. Incubation under oxygen-depleted conditions caused a marked decrease in both PHA-induced superoxide generation and cytotoxicity relative to that obtained with neutrophils incubated aerobically. These findings suggest a central role for superoxide radicals in causing target cell damage in this model of neutrophil-mediated cytotoxicity.", "contents": "Evidence for the role of superoxide radicals in neutrophil-mediated cytotoxicity. Human peripheral neutrophils became cytotoxic to chicken red blood cells (CRBC) in the presence of lectins as assessed by release of 51chromium from labelled target cells. Phytohaemagglutinin (PHA) and concanavalin A (Con A), which caused time-dependent and dose-dependent cytotoxicity over a concentration range of 25--400 microgram/ml, also caused significant generation of superoxide radicals as measured by ferricytochrome C reduction. Pokeweed mitogen, which does not induce cytotoxicity over the same concentration range, was unable to promote superoxide generation by neutrophils. PHA-induced generation of superoxide paralleled and appeared to precede PHA-dependent cytotoxicity. Superoxide dismutase (SOD), which enzymatically destroys superoxide, caused moderate inhibition of PHA-dependent cytotoxicity over the concentration range of 100--500 microgram/ml whereas catalytically inactive enzyme had no effect. Incubation under oxygen-depleted conditions caused a marked decrease in both PHA-induced superoxide generation and cytotoxicity relative to that obtained with neutrophils incubated aerobically. These findings suggest a central role for superoxide radicals in causing target cell damage in this model of neutrophil-mediated cytotoxicity."}
{"id": "PMID:223977", "title": "Studies on the mechanism of macrophage aggregation induced by lymphokines.", "content": "Macrophage aggregation (measured by a light-scattering technique) induced by unpurified lymphokine preparations has been investigated. This has been shown to be Ca2+ or Mg2+ dependent and to be inhibited by a number of agents known to affect cellular physiology and biochemistry. The divalent cation ionophore A23187 causes a macrophage aggregation superficially similar to that induced by lymphokines, although differences were found. It is suggested that a biochemical response by the macrophage is required for aggregation induced by lymphokines, and thus measurements of macrophage aggregation allow a study of the early events in the response of macrophages to lymphokines.", "contents": "Studies on the mechanism of macrophage aggregation induced by lymphokines. Macrophage aggregation (measured by a light-scattering technique) induced by unpurified lymphokine preparations has been investigated. This has been shown to be Ca2+ or Mg2+ dependent and to be inhibited by a number of agents known to affect cellular physiology and biochemistry. The divalent cation ionophore A23187 causes a macrophage aggregation superficially similar to that induced by lymphokines, although differences were found. It is suggested that a biochemical response by the macrophage is required for aggregation induced by lymphokines, and thus measurements of macrophage aggregation allow a study of the early events in the response of macrophages to lymphokines."}
{"id": "PMID:223980", "title": "Molecular approach to the epidemiology of swine vesicular disease: correlation of variation in the virus structural polypeptides with serological properties.", "content": "Variation has been observed in the structural polypeptides of swine vesicular disease viruses isolated from the United Kingdom and Hong Kong. Despite the limited number of isolates examined, several distinct polypeptide patterns were obtained when the virus structural proteins were examined by polyacrylamide gel electrophoresis. Isolates from outbreaks in the United Kingdom which were known to be connected gave the same polypeptide pattern, whereas viruses with different polypeptide patterns could not be traced to a common source. The different polypeptide patterns were obtained consistently and were not altered by passage of the virus in tissue culture. In general, isolates with identical polypeptide patterns could not be distinguished by neutralization or antibody blocking tests or by competition radioimmunoassays. However, isolates with different polypeptide patterns could be differentiated by antibody blocking tests or radioimmunoassay. The correlation between the serological tests and the polyacrylamide gel electrophoresis analyses illustrates the value of analyzing structural polypeptides in the epidemiological study of swine vesicular disease.", "contents": "Molecular approach to the epidemiology of swine vesicular disease: correlation of variation in the virus structural polypeptides with serological properties. Variation has been observed in the structural polypeptides of swine vesicular disease viruses isolated from the United Kingdom and Hong Kong. Despite the limited number of isolates examined, several distinct polypeptide patterns were obtained when the virus structural proteins were examined by polyacrylamide gel electrophoresis. Isolates from outbreaks in the United Kingdom which were known to be connected gave the same polypeptide pattern, whereas viruses with different polypeptide patterns could not be traced to a common source. The different polypeptide patterns were obtained consistently and were not altered by passage of the virus in tissue culture. In general, isolates with identical polypeptide patterns could not be distinguished by neutralization or antibody blocking tests or by competition radioimmunoassays. However, isolates with different polypeptide patterns could be differentiated by antibody blocking tests or radioimmunoassay. The correlation between the serological tests and the polyacrylamide gel electrophoresis analyses illustrates the value of analyzing structural polypeptides in the epidemiological study of swine vesicular disease."}
{"id": "PMID:223981", "title": "Leukocyte cytotoxicity in a persistent virus infection: presence of direct cytotoxicity but absence of antibody-dependent cellular cytotoxicity in horses infected with equine infectious anemia virus.", "content": "Antibody-dependent cellular cytotoxicity and direct cytotoxicity assays were performed with equine infectious anemia virus-infected target cells, equine leukocytes, and equine anti-equine infectious anemia virus antibody to determine whether these mechanisms play a role in controlling viral replication in equine infectious anemia. Direct cytotoxicity was observed by using peripheral blood mononuclear cells from 7 of 10 infected horses. Antibody-dependent cellular cytotoxicity was not observed. The antibody-dependent cellular cytotoxicity reaction in horses was then studied by using sheep erythrocytes and trinitrophenylated sheep erythrocytes as target cells. Lysis of these target cells was mediated by neutrophils, monocytes, and lymphocytes. The reaction was activated by antibody of the immunoglobulin G class but not by immunoglobulin G(T). Furthermore, immunoglobulin G(T) efficiently inhibited immunoglobulin G in this function.", "contents": "Leukocyte cytotoxicity in a persistent virus infection: presence of direct cytotoxicity but absence of antibody-dependent cellular cytotoxicity in horses infected with equine infectious anemia virus. Antibody-dependent cellular cytotoxicity and direct cytotoxicity assays were performed with equine infectious anemia virus-infected target cells, equine leukocytes, and equine anti-equine infectious anemia virus antibody to determine whether these mechanisms play a role in controlling viral replication in equine infectious anemia. Direct cytotoxicity was observed by using peripheral blood mononuclear cells from 7 of 10 infected horses. Antibody-dependent cellular cytotoxicity was not observed. The antibody-dependent cellular cytotoxicity reaction in horses was then studied by using sheep erythrocytes and trinitrophenylated sheep erythrocytes as target cells. Lysis of these target cells was mediated by neutrophils, monocytes, and lymphocytes. The reaction was activated by antibody of the immunoglobulin G class but not by immunoglobulin G(T). Furthermore, immunoglobulin G(T) efficiently inhibited immunoglobulin G in this function."}
{"id": "PMID:223982", "title": "Effect of viruses on luminol-dependent chemiluminescence of human neutrophils.", "content": "The effects of Newcastle disease, herpes simplex, vaccinia, encephalomyocarditis, vesicular stomatitis and reoviruses on in vitro function of neutrophils were studied in Ficoll-Hypaque-separated polymorphonuclear leukocytes (PMN) employing the technique of luminol-dependent chemiluminescence. Newcastle disease, herpes simplex vaccinia, and reoviruses depressed chemiluminescence by 98, 65, 46, and 29%, respectively, while encephalomyocarditis and vesicular stomatitis viruses had no inhibitory effect. None of the viruses affected phagocytosis or PMN viability. These observations suggest significant alteration of neutrophil function by interaction with several viruses in in vitro settings. It is suggested that similar changes in PMN function may occur during in vivo viral infection.", "contents": "Effect of viruses on luminol-dependent chemiluminescence of human neutrophils. The effects of Newcastle disease, herpes simplex, vaccinia, encephalomyocarditis, vesicular stomatitis and reoviruses on in vitro function of neutrophils were studied in Ficoll-Hypaque-separated polymorphonuclear leukocytes (PMN) employing the technique of luminol-dependent chemiluminescence. Newcastle disease, herpes simplex vaccinia, and reoviruses depressed chemiluminescence by 98, 65, 46, and 29%, respectively, while encephalomyocarditis and vesicular stomatitis viruses had no inhibitory effect. None of the viruses affected phagocytosis or PMN viability. These observations suggest significant alteration of neutrophil function by interaction with several viruses in in vitro settings. It is suggested that similar changes in PMN function may occur during in vivo viral infection."}
{"id": "PMID:223983", "title": "Interaction between 6/94 virus, a parainfluenza type 1 strain, and mouse macrophages.", "content": "The 6/94 virus, a type 1 parainfluenza virus recovered from multiple sclerosis brain cells after lysolecithin-induced fusion of these cells with African green monkey kidney cells (CV-1), has been found to grow in splenic and peritoneal macrophages obtained from outbred and different strains of inbred mice. Macrophages from C57BL animals were least susceptible to infection, a resistance apparently partially age related. The virus also has been found to replicate in IC21 cells, a line of simian virus 40 virus-transformed mouse macrophages. Viral growth was detected by development of hemadsorption in infected cells, followed by the appearance of infectious virus. The growth of 6/94 virus had different kinetics in mouse macrophages, in the standard continuous cell lines L, 3T3, and CV-1, and in primary mouse kidney and mouse embryo cells. The virus produced in macrophages could be passed in series to other macrophage cultures. In addition, once infected, the cultures continued to produce virus, and permanently infected cell lines were thus obtained. Macrophages from immunized mice with high titers of humoral neutralizing antibodies were found variably able to support virus growth.", "contents": "Interaction between 6/94 virus, a parainfluenza type 1 strain, and mouse macrophages. The 6/94 virus, a type 1 parainfluenza virus recovered from multiple sclerosis brain cells after lysolecithin-induced fusion of these cells with African green monkey kidney cells (CV-1), has been found to grow in splenic and peritoneal macrophages obtained from outbred and different strains of inbred mice. Macrophages from C57BL animals were least susceptible to infection, a resistance apparently partially age related. The virus also has been found to replicate in IC21 cells, a line of simian virus 40 virus-transformed mouse macrophages. Viral growth was detected by development of hemadsorption in infected cells, followed by the appearance of infectious virus. The growth of 6/94 virus had different kinetics in mouse macrophages, in the standard continuous cell lines L, 3T3, and CV-1, and in primary mouse kidney and mouse embryo cells. The virus produced in macrophages could be passed in series to other macrophage cultures. In addition, once infected, the cultures continued to produce virus, and permanently infected cell lines were thus obtained. Macrophages from immunized mice with high titers of humoral neutralizing antibodies were found variably able to support virus growth."}
{"id": "PMID:223984", "title": "Interaction between 6/94 virus, a parainfluenza type 1 strain, and unstimulated mouse lymphocytes.", "content": "6/94 virus was found to grow in unstimulated splenic mouse lymphocytes depleted of monocyte macrophages. Both egg-grown virus and virus produced in mouse macrophage cultures induced the development of hemadsorption and the appearance of new infectious virus in the lymphocyte cultures. An antigenic relative. Sendai virus, on the contrary, was quickly inactivated in these lymphocyte cultures, in agreement with previous reports in the literature. The T lymphocyte population seemed to be the fraction principally involved in the replication of 6/94 virus. The immunization of mice with 6/94 virus and the appearance of high levels of humoral neutralizing antibodies did not inhibit completely the susceptibility of their lymphocytes to the infectious agent.", "contents": "Interaction between 6/94 virus, a parainfluenza type 1 strain, and unstimulated mouse lymphocytes. 6/94 virus was found to grow in unstimulated splenic mouse lymphocytes depleted of monocyte macrophages. Both egg-grown virus and virus produced in mouse macrophage cultures induced the development of hemadsorption and the appearance of new infectious virus in the lymphocyte cultures. An antigenic relative. Sendai virus, on the contrary, was quickly inactivated in these lymphocyte cultures, in agreement with previous reports in the literature. The T lymphocyte population seemed to be the fraction principally involved in the replication of 6/94 virus. The immunization of mice with 6/94 virus and the appearance of high levels of humoral neutralizing antibodies did not inhibit completely the susceptibility of their lymphocytes to the infectious agent."}
{"id": "PMID:223985", "title": "Interaction between 6/94 virus, a parainfluenza type 1 strain, and human leukocytes.", "content": "6/94 virus, a parainfluenza type 1 virus recovered by lysolecithin fusion of multiple sclerosis brain cell cultures with CV-1 cells, replicated in monocyte macrophages and lymphocytes from normal human donors and from a patient with multiple sclerosis. In macrophage cultures, hemadsorption-positive cells and high levels of infectious virus became apparent within 24 to 48 h after infection, persisted for 6 days, and then began to decrease. Phytohemagglutinin-stimulated macrophages yielded similar titers of virus, but the levels were maintained for a longer period of time. Macrophage-produced virus appeared to be infectious for other macrophages in the same culture. Both unstimulated and phytohemagglutinin-stimulated lymphocytes also supported virus replication. Significantly higher titers were produced in the stimulated cultures, T cell-enriched populations producing more virus than unseparated populations whether stimulated or unstimulated. The presence or absence of antibodies to the virus in the donors did not appear to influence the levels of virus obtained in any of the leukocyte cultures. However, an increase in blastic forms after 6/94 virus infection was noted in lymphocytes from donors with antibodies as revealed morphologically and by increased incorporations of tritiated thymidine. Furthermore, 6/94 virus-infected lymphocytes, unlike Sendai virus-infected lymphocytes, were able to respond well to mitogenic stimulation by phytohemagglutinin.", "contents": "Interaction between 6/94 virus, a parainfluenza type 1 strain, and human leukocytes. 6/94 virus, a parainfluenza type 1 virus recovered by lysolecithin fusion of multiple sclerosis brain cell cultures with CV-1 cells, replicated in monocyte macrophages and lymphocytes from normal human donors and from a patient with multiple sclerosis. In macrophage cultures, hemadsorption-positive cells and high levels of infectious virus became apparent within 24 to 48 h after infection, persisted for 6 days, and then began to decrease. Phytohemagglutinin-stimulated macrophages yielded similar titers of virus, but the levels were maintained for a longer period of time. Macrophage-produced virus appeared to be infectious for other macrophages in the same culture. Both unstimulated and phytohemagglutinin-stimulated lymphocytes also supported virus replication. Significantly higher titers were produced in the stimulated cultures, T cell-enriched populations producing more virus than unseparated populations whether stimulated or unstimulated. The presence or absence of antibodies to the virus in the donors did not appear to influence the levels of virus obtained in any of the leukocyte cultures. However, an increase in blastic forms after 6/94 virus infection was noted in lymphocytes from donors with antibodies as revealed morphologically and by increased incorporations of tritiated thymidine. Furthermore, 6/94 virus-infected lymphocytes, unlike Sendai virus-infected lymphocytes, were able to respond well to mitogenic stimulation by phytohemagglutinin."}
{"id": "PMID:223986", "title": "Immunity to foot-and-mouth disease virus in guinea pigs: clinical and immune responses.", "content": "Clinical and immune responses were determined for guinea pigs infected with different doses of foot-and-mouth disease virus (FMDV) type A12, strain 119, administered by different routes. Vesicles developed on the tongue or heel pad 1 day after these areas were intradermally inoculated with FMDV. However, vesicles did not develop on the feet and tongue until 3 to 4 days after the intradermal inoculation of FMDV in the flank skin or after intracardiac or subcutaneous inoculation. Infected guinea pigs developed neutralizing antibody, immediate skin reactivity of the Arthus type (4 h), and delayed skin reactivity. In addition to a delayed skin response, the presence of a cell-mediated immune response to FMDV was shown by the specific production of macrophage migration inhibition factor by peritoneal exudate cells in response to FMDV. Kinetic studies showed that neutralizing antibodies were detected at 3 days postinfection, and Arthus and delayed skin reactivity were detected at 4 days postinfection. Some guinea pigs developed either mild or subclinical infections. Regardless of the dose of infectious virus, the route of inoculation, the severity of disease, or the time of clinical onset of disease, infected guinea pigs developed similar immune responses.", "contents": "Immunity to foot-and-mouth disease virus in guinea pigs: clinical and immune responses. Clinical and immune responses were determined for guinea pigs infected with different doses of foot-and-mouth disease virus (FMDV) type A12, strain 119, administered by different routes. Vesicles developed on the tongue or heel pad 1 day after these areas were intradermally inoculated with FMDV. However, vesicles did not develop on the feet and tongue until 3 to 4 days after the intradermal inoculation of FMDV in the flank skin or after intracardiac or subcutaneous inoculation. Infected guinea pigs developed neutralizing antibody, immediate skin reactivity of the Arthus type (4 h), and delayed skin reactivity. In addition to a delayed skin response, the presence of a cell-mediated immune response to FMDV was shown by the specific production of macrophage migration inhibition factor by peritoneal exudate cells in response to FMDV. Kinetic studies showed that neutralizing antibodies were detected at 3 days postinfection, and Arthus and delayed skin reactivity were detected at 4 days postinfection. Some guinea pigs developed either mild or subclinical infections. Regardless of the dose of infectious virus, the route of inoculation, the severity of disease, or the time of clinical onset of disease, infected guinea pigs developed similar immune responses."}
{"id": "PMID:223987", "title": "Characteristics of infection of B and T lymphocytes from mice after inoculation with cytomegalovirus.", "content": "Viremia was produced by inoculating intravenously BALB/c mice with murine cytomegalovirus. Virus was detected in plasma and granulocytes only during the first 8 days after infection. Lymphocyte-associated viremia, detectable by cocultivation on syngeneic or allogeneic fibroblasts, persisted for at least 4 weeks. Eight to 10 days after infection, sonicated lymphocytes had no demonstrable free virus. When whole lymphocytes with no demonstrable free virus were enclosed in a Millipore chamber and placed on a fibroblastic feeder layer, T cells produced free virus but B cells did not. Compared to normal calf serum, specific hyperimmune serum reduced B cell-associated infectious centers by 74% and T cell-associated infectious centers by only 38%. Normal mouse sera reduced by 36% and 30% infectious center production by B cells and T cells, respectively. Lymphocytes enriched with Fc receptor-positive cells produced significantly more infectious centers than receptor-negative cells.", "contents": "Characteristics of infection of B and T lymphocytes from mice after inoculation with cytomegalovirus. Viremia was produced by inoculating intravenously BALB/c mice with murine cytomegalovirus. Virus was detected in plasma and granulocytes only during the first 8 days after infection. Lymphocyte-associated viremia, detectable by cocultivation on syngeneic or allogeneic fibroblasts, persisted for at least 4 weeks. Eight to 10 days after infection, sonicated lymphocytes had no demonstrable free virus. When whole lymphocytes with no demonstrable free virus were enclosed in a Millipore chamber and placed on a fibroblastic feeder layer, T cells produced free virus but B cells did not. Compared to normal calf serum, specific hyperimmune serum reduced B cell-associated infectious centers by 74% and T cell-associated infectious centers by only 38%. Normal mouse sera reduced by 36% and 30% infectious center production by B cells and T cells, respectively. Lymphocytes enriched with Fc receptor-positive cells produced significantly more infectious centers than receptor-negative cells."}
{"id": "PMID:223988", "title": "Shigella infection of henle intestinal epithelial cells: role of the host cell.", "content": "The process of Henle 407 embryonic intestinal epithelial cell infection by Shigella flexneri 2a M42-43 was studied in an in vitro model system. The role of the Henle cell was assessed. It was established that entry of S. flexneri into cells was suppressed by reagents which inhibit uptake of particles by phagocytic cells. The compounds tested included cytochalasin B, dibutyryl-cyclic adenosine monophosphate, choleragen (Vibrio cholera enterotoxin), iodoacetate, and dinitrophenol. Cytochalasin B inhibited infection at concentrations of 1.0 mug/ml or greater. Dibutyryl-cyclic adenosine monophosphate at concentrations of 1 mM and choleragen at 0.1 mug/ml caused significant suppression of infection. Iodoacetate or dinitrophenol, at 0.1 mM concentrations, inhibited internalization of virulent shigellae, and a combination of these compounds inhibited infection at 0.01 mM concentrations. Preincubation of Henle cell monolayers with the combination of iodoacetate and dinitrophenol (0.05 mM) also inhibited infection markedly. The data suggest that infection of epithelial cells by S. flexneri in vitro is accomplished by an endocytic process induced by virulent bacteria. The process appears to be similar to uptake of particles by phagocytic cells. Ultrastructural analysis by transmission electron microscopy provided corroborative evidence of phagocytosis of shigellae by Henle cells in that intracellular bacteria were often observed within membrane-limiting vacuoles resembling phagosomes.", "contents": "Shigella infection of henle intestinal epithelial cells: role of the host cell. The process of Henle 407 embryonic intestinal epithelial cell infection by Shigella flexneri 2a M42-43 was studied in an in vitro model system. The role of the Henle cell was assessed. It was established that entry of S. flexneri into cells was suppressed by reagents which inhibit uptake of particles by phagocytic cells. The compounds tested included cytochalasin B, dibutyryl-cyclic adenosine monophosphate, choleragen (Vibrio cholera enterotoxin), iodoacetate, and dinitrophenol. Cytochalasin B inhibited infection at concentrations of 1.0 mug/ml or greater. Dibutyryl-cyclic adenosine monophosphate at concentrations of 1 mM and choleragen at 0.1 mug/ml caused significant suppression of infection. Iodoacetate or dinitrophenol, at 0.1 mM concentrations, inhibited internalization of virulent shigellae, and a combination of these compounds inhibited infection at 0.01 mM concentrations. Preincubation of Henle cell monolayers with the combination of iodoacetate and dinitrophenol (0.05 mM) also inhibited infection markedly. The data suggest that infection of epithelial cells by S. flexneri in vitro is accomplished by an endocytic process induced by virulent bacteria. The process appears to be similar to uptake of particles by phagocytic cells. Ultrastructural analysis by transmission electron microscopy provided corroborative evidence of phagocytosis of shigellae by Henle cells in that intracellular bacteria were often observed within membrane-limiting vacuoles resembling phagosomes."}
{"id": "PMID:223989", "title": "A rat model for study of bilirubin conjugation by a cultured cell/ artificial capillary liver assist device.", "content": "The Gunn rat, congenitally lacking the conjugating enzyme glucuronyl transferase, provides an animal model for the study of bilirubin conjugation by an extracorporeal liver assist device (LAD) composed of cultured cells and artificial capillaries. Rat hepatoma cells of the H4-II-E cell line able to form conjugated bilirubin glucuronide from bilirubin were grown to tissue density by circumfusion culture of the LAD before symbiotic hemoperfusion experiments lasting up to 24 hours. Rat bile was analyzed by thin layer chromatography for bilirubin glucuronide which was formed by the device and then excreted by the rat.", "contents": "A rat model for study of bilirubin conjugation by a cultured cell/ artificial capillary liver assist device. The Gunn rat, congenitally lacking the conjugating enzyme glucuronyl transferase, provides an animal model for the study of bilirubin conjugation by an extracorporeal liver assist device (LAD) composed of cultured cells and artificial capillaries. Rat hepatoma cells of the H4-II-E cell line able to form conjugated bilirubin glucuronide from bilirubin were grown to tissue density by circumfusion culture of the LAD before symbiotic hemoperfusion experiments lasting up to 24 hours. Rat bile was analyzed by thin layer chromatography for bilirubin glucuronide which was formed by the device and then excreted by the rat."}
{"id": "PMID:223990", "title": "Simultaneous presence of EBNA-positive and colony-forming cells in peripheral blood of patients with infectious mononucleosis.", "content": "EBNA-positive lymphoblast cells were detected in 0.1 to 0.9% of the T-cell-depleted lymphocytes obtained from peripheral blood samples of five patients with infectious mononucleosis (IM). The same blood specimens from four of the five patients contained cells that formed EBNA-positive colonies in soft agar containing EBV antibodies. The ratio of the colony formers to EBNA-positive cells was higher in blood samples taken early in the disease than in those obtained in later stages of the disease. The present results strongly suggest that EBV-transformed cells are present in the peripheral circulation of IM patients and that such cells can directly give rise to immortalized cell lines in vitro.", "contents": "Simultaneous presence of EBNA-positive and colony-forming cells in peripheral blood of patients with infectious mononucleosis. EBNA-positive lymphoblast cells were detected in 0.1 to 0.9% of the T-cell-depleted lymphocytes obtained from peripheral blood samples of five patients with infectious mononucleosis (IM). The same blood specimens from four of the five patients contained cells that formed EBNA-positive colonies in soft agar containing EBV antibodies. The ratio of the colony formers to EBNA-positive cells was higher in blood samples taken early in the disease than in those obtained in later stages of the disease. The present results strongly suggest that EBV-transformed cells are present in the peripheral circulation of IM patients and that such cells can directly give rise to immortalized cell lines in vitro."}
{"id": "PMID:223991", "title": "Relationship between the Epstein-Barr virus genome and nasopharyngeal carcinoma in Caucasian patients.", "content": "In order to explore whether undifferentiated nasopharyngeal carcinoma (NPC) shows a regular association with Epstein-Barr virus (EBV), regardless of the geographical and ethnic origin of the patient, a correlated histopathological and nucleic acid hybridization study was performed on biopsies from Caucasian patients with nasopharyngeal carcinomas and from various controls. Among 12 undifferentiated NPCs, 11 were positive for EBV-DNA, with multiple copies of the viral genome per cell. Serological tests showed elevated anti-VCA and anti-EA(DA) titers. Six NPCs with various degrees of squamous differentiation, four malignant lymphomas of the nasopharynx and seven carcinomas located outside the nasopharynx were EBV-DNA negative. These findings further stress the uniqueness and regularity of the association between EBV-DNA and undifferentiated NPC. Clearly, the association extends over geographical barriers and holds true not only in the previously studied, moderate-incidence African ethnic group, but also in the low-incidence Western patients.", "contents": "Relationship between the Epstein-Barr virus genome and nasopharyngeal carcinoma in Caucasian patients. In order to explore whether undifferentiated nasopharyngeal carcinoma (NPC) shows a regular association with Epstein-Barr virus (EBV), regardless of the geographical and ethnic origin of the patient, a correlated histopathological and nucleic acid hybridization study was performed on biopsies from Caucasian patients with nasopharyngeal carcinomas and from various controls. Among 12 undifferentiated NPCs, 11 were positive for EBV-DNA, with multiple copies of the viral genome per cell. Serological tests showed elevated anti-VCA and anti-EA(DA) titers. Six NPCs with various degrees of squamous differentiation, four malignant lymphomas of the nasopharynx and seven carcinomas located outside the nasopharynx were EBV-DNA negative. These findings further stress the uniqueness and regularity of the association between EBV-DNA and undifferentiated NPC. Clearly, the association extends over geographical barriers and holds true not only in the previously studied, moderate-incidence African ethnic group, but also in the low-incidence Western patients."}
{"id": "PMID:223992", "title": "Macrophage-dependent, NK-cell-independent \"natural\" surveillance of tumors in syngeneic mice.", "content": "The present study, which was designed to further characterize the \"natural\" T-independent rejection of syngenetic tumours (Greenberg and Greene, 1976), has revealed the following points: (1) no detectable DBA/2 NK cell activity was demonstrated against the syngeneic tumour lines studied, and these tumours were indensitive to NK cells from high-activity strains; (2) in addition the tumour frequencies in old and young mice receiving small tumour inocula were identical, in contrast with the reported decline in NK cell activity with age, suggesting that the surveillance of small inocula of these tumours was NK-cell-independent; (3) injection of silica intraperitoneally enhanced the frequency of tumours in normal and immunodeficient AT x BM mice, suggesting that the rejection mechanism was macrophage-dependent; (4) the effects of silica injection were maximal if administered 3 days prior to tumour injection, indicating that the period of time in which the rejection mechanism must act was very limited; (5) silica markedly decreased the survival of AKR mice dying of spontaneous tumours, providing evidence that the effect of this agent was not limited to model systems but would influence the appearance of spontaneous tumours; (6) reticuloendothelial stimulants such as mycobacterium butyricum and proteose peptone decreased the tumour frequency of small tumour inocula, indicating that the effector mechanism can be stimulated; and (7) soluble tumour antigen enhanced the tumour frequency in normal and immunodeficient mice, suggesting that the specific receptor molecule of the surveillance mechanism was not thymus-dependent.", "contents": "Macrophage-dependent, NK-cell-independent \"natural\" surveillance of tumors in syngeneic mice. The present study, which was designed to further characterize the \"natural\" T-independent rejection of syngenetic tumours (Greenberg and Greene, 1976), has revealed the following points: (1) no detectable DBA/2 NK cell activity was demonstrated against the syngeneic tumour lines studied, and these tumours were indensitive to NK cells from high-activity strains; (2) in addition the tumour frequencies in old and young mice receiving small tumour inocula were identical, in contrast with the reported decline in NK cell activity with age, suggesting that the surveillance of small inocula of these tumours was NK-cell-independent; (3) injection of silica intraperitoneally enhanced the frequency of tumours in normal and immunodeficient AT x BM mice, suggesting that the rejection mechanism was macrophage-dependent; (4) the effects of silica injection were maximal if administered 3 days prior to tumour injection, indicating that the period of time in which the rejection mechanism must act was very limited; (5) silica markedly decreased the survival of AKR mice dying of spontaneous tumours, providing evidence that the effect of this agent was not limited to model systems but would influence the appearance of spontaneous tumours; (6) reticuloendothelial stimulants such as mycobacterium butyricum and proteose peptone decreased the tumour frequency of small tumour inocula, indicating that the effector mechanism can be stimulated; and (7) soluble tumour antigen enhanced the tumour frequency in normal and immunodeficient mice, suggesting that the specific receptor molecule of the surveillance mechanism was not thymus-dependent."}
{"id": "PMID:223993", "title": "Effect of interferon on chronic infection of human cells by xenotropic type-C viruses.", "content": "Different preparations of human interferon inhibit virus production in human cells chronically infected by a variety of type-C xenotropic viruses. Some of these viruses have been incriminated in the development of leukemia in primates. The characteristics of blocking of viral multiplication are similar to those described for the effect of mouse interferon on ecotropic viruses. The amount of free virus in culture supernatants is strongly decreased while intracellular protein p30 stays unchanged or is slightly increased. On the other hand, the inhibitory effect is reversible. The withdrawal of interferon results in a rapid increase in virus production as detectable in supernatant fluids. In the light of these results it is suggested that human interferon might be useful in the treatment of some blood malignancies suspected of being related to infection with xenotropic type-C viruses.", "contents": "Effect of interferon on chronic infection of human cells by xenotropic type-C viruses. Different preparations of human interferon inhibit virus production in human cells chronically infected by a variety of type-C xenotropic viruses. Some of these viruses have been incriminated in the development of leukemia in primates. The characteristics of blocking of viral multiplication are similar to those described for the effect of mouse interferon on ecotropic viruses. The amount of free virus in culture supernatants is strongly decreased while intracellular protein p30 stays unchanged or is slightly increased. On the other hand, the inhibitory effect is reversible. The withdrawal of interferon results in a rapid increase in virus production as detectable in supernatant fluids. In the light of these results it is suggested that human interferon might be useful in the treatment of some blood malignancies suspected of being related to infection with xenotropic type-C viruses."}
{"id": "PMID:223995", "title": "Enhancement by asbestos of oncogenesis by Moloney murine sarcoma virus in CBA mice.", "content": "Five micrograms of finely ground crocidolite asbestos (UICC standard sample) were injected intraperitoneally into 3-week-old CBA mice, together with 10(5) FFU of Moloney murine sarcoma virus. Altogether 44 out of 61 mice (72.1%) so treated developed palpable intraperitoneal tumours, and half of these died of such tumours within 100 days. The same amount of quartz and carbon similarly administered gave lower tumour incidences, namely, 19.4% (3.2% fatal) and 11.9% (1.5% fatal) respectively. Only 1 out of 59 mice inoculated with the virus alone developed a palpable intraperitoneal tumour, and this regressed spontaneously within 10 days of its first appearance. No tumours were encountered in mice treated with either asbestos, quartz or carbon alone. All the neoplasms had the appearance, under the light microscope, of anaplastic sarcomas. Most of them were confined to the serosal surface of the abdominal cavity, although invasion of underlying tissues was observed in some of the animals that died. Electron microscopical examination of tumours revealed the presence of C-type particles budding off from cellular surface. Some neoplastic cells showed characteristic features of mesothelial lining cells. The role of milky spots (taches laiteuses) in oncogenesis by asbestos and virus, especially in the induction of mesothelioma, is discussed.", "contents": "Enhancement by asbestos of oncogenesis by Moloney murine sarcoma virus in CBA mice. Five micrograms of finely ground crocidolite asbestos (UICC standard sample) were injected intraperitoneally into 3-week-old CBA mice, together with 10(5) FFU of Moloney murine sarcoma virus. Altogether 44 out of 61 mice (72.1%) so treated developed palpable intraperitoneal tumours, and half of these died of such tumours within 100 days. The same amount of quartz and carbon similarly administered gave lower tumour incidences, namely, 19.4% (3.2% fatal) and 11.9% (1.5% fatal) respectively. Only 1 out of 59 mice inoculated with the virus alone developed a palpable intraperitoneal tumour, and this regressed spontaneously within 10 days of its first appearance. No tumours were encountered in mice treated with either asbestos, quartz or carbon alone. All the neoplasms had the appearance, under the light microscope, of anaplastic sarcomas. Most of them were confined to the serosal surface of the abdominal cavity, although invasion of underlying tissues was observed in some of the animals that died. Electron microscopical examination of tumours revealed the presence of C-type particles budding off from cellular surface. Some neoplastic cells showed characteristic features of mesothelial lining cells. The role of milky spots (taches laiteuses) in oncogenesis by asbestos and virus, especially in the induction of mesothelioma, is discussed."}
{"id": "PMID:223996", "title": "Therapy of adrenocortical hydroxylase deficiencies in acne vulgaris.", "content": "Twenty women with acne vulgaris who presented to a gynecologist's office with the complaints of hirsutism, infertility, menorrhagia, or oligomenorrhea were subjected to a 24-hour cosyntropin (ACTH) infusion to detect partial 11- or 21-adrenocortical hydroxylase deficiencies. All patients demonstrated enzymatic defects and were placed on prednisone therapy. The six patients with moderate acne either showed improvement of their acne or conceived. Of the 14 patients with mild acne, seven showed improvement of their acne or conceived; whereas, the remainder showed no improvement. Patients with acne and gynecologic signs and symptoms should be evaluated for the presence of 11- or 21-adrenocortical hydroxylase deficiencies.", "contents": "Therapy of adrenocortical hydroxylase deficiencies in acne vulgaris. Twenty women with acne vulgaris who presented to a gynecologist's office with the complaints of hirsutism, infertility, menorrhagia, or oligomenorrhea were subjected to a 24-hour cosyntropin (ACTH) infusion to detect partial 11- or 21-adrenocortical hydroxylase deficiencies. All patients demonstrated enzymatic defects and were placed on prednisone therapy. The six patients with moderate acne either showed improvement of their acne or conceived. Of the 14 patients with mild acne, seven showed improvement of their acne or conceived; whereas, the remainder showed no improvement. Patients with acne and gynecologic signs and symptoms should be evaluated for the presence of 11- or 21-adrenocortical hydroxylase deficiencies."}
{"id": "PMID:223997", "title": "Granular cell tumor of the tongue.", "content": "The granular cell tumor has been and still is a debatable lesion in several aspects. The etiology and pathogenesis are still unknown. Granular cell tumors may occur everywhere in the body, but the oral cavity is a favorite location. The majority of the oral lesions are found in the dorsum and the borders of the anterior two-thirds of the tongue. Seven patients with a granular cell tumor of the tongue are described. The clinical and microscopic findings have been discussed. In all cases an excisional biopsy had been aimed at. In spite of incomplete excision in six out of the seven cases, local recurrences were noticed in only one patient. In one patient \"metastatic\" occurrence of granular cell tumors was noticed.", "contents": "Granular cell tumor of the tongue. The granular cell tumor has been and still is a debatable lesion in several aspects. The etiology and pathogenesis are still unknown. Granular cell tumors may occur everywhere in the body, but the oral cavity is a favorite location. The majority of the oral lesions are found in the dorsum and the borders of the anterior two-thirds of the tongue. Seven patients with a granular cell tumor of the tongue are described. The clinical and microscopic findings have been discussed. In all cases an excisional biopsy had been aimed at. In spite of incomplete excision in six out of the seven cases, local recurrences were noticed in only one patient. In one patient \"metastatic\" occurrence of granular cell tumors was noticed."}
{"id": "PMID:223998", "title": "Follow-up study of 14 oral granular cell tumors.", "content": "The granular cell tumor is an uncommon benign lesion with a predilection for the oral cavity. Fourteen tumors from 13 patients have been reviewed with a follow-up period ranging from 7 months to 21 years with an average of 7.1 years. Women were affected twice as often as men, and the age of the patients varied from 14 to 75 years. Eleven of the lesions were located on the tongue, the remaining on the lower lip, sublingual papilla, and the buccal mucosa. Multiple lesions were found in one patient.The tumors varied in size from 3 to 25 mm in diameter and were all firm to hard in consistency. All the lesions were treated by local excision. Pseudoepitheliomatous hyperplasia of the overlying epithelium was seen in four patients. In spite of a possible inadequate removal of 10 of the lesions where granular cells extended to the margin of excision, no recurrence was seen. A simple but deep local excision is the recommended treatment.", "contents": "Follow-up study of 14 oral granular cell tumors. The granular cell tumor is an uncommon benign lesion with a predilection for the oral cavity. Fourteen tumors from 13 patients have been reviewed with a follow-up period ranging from 7 months to 21 years with an average of 7.1 years. Women were affected twice as often as men, and the age of the patients varied from 14 to 75 years. Eleven of the lesions were located on the tongue, the remaining on the lower lip, sublingual papilla, and the buccal mucosa. Multiple lesions were found in one patient.The tumors varied in size from 3 to 25 mm in diameter and were all firm to hard in consistency. All the lesions were treated by local excision. Pseudoepitheliomatous hyperplasia of the overlying epithelium was seen in four patients. In spite of a possible inadequate removal of 10 of the lesions where granular cells extended to the margin of excision, no recurrence was seen. A simple but deep local excision is the recommended treatment."}
{"id": "PMID:223999", "title": "Two qualitatively different effects of hyperthermia on acid phosphatase staining in mouse spleen, dependent on the severity of the treatment.", "content": "Heating the lower body of the mouse for up to 1.5 hours at temperatures above 41.0 degrees C causes an increase in splenic lysosomal acid phosphatase activity. For mouse temperatures up to 42.3 degrees C the change is probably due to enzyme activation, which reaches a maximum 1.5 hours after heating and then decays in a way which may be related to the transient ability of moderate hyperthermia to potentiate X-ray damage. At temperatures above about 42.5 degrees C hyperthermia results in a qualitatively different lysomal response, probably due to an increased lysosomal membrane permeability. The change is observed immediately after heating and remains high for at least 4 hours. The resultant release of hydrolases into the cytoplasm may be involved in the irreversible cell damage caused by severe hyperthermia.", "contents": "Two qualitatively different effects of hyperthermia on acid phosphatase staining in mouse spleen, dependent on the severity of the treatment. Heating the lower body of the mouse for up to 1.5 hours at temperatures above 41.0 degrees C causes an increase in splenic lysosomal acid phosphatase activity. For mouse temperatures up to 42.3 degrees C the change is probably due to enzyme activation, which reaches a maximum 1.5 hours after heating and then decays in a way which may be related to the transient ability of moderate hyperthermia to potentiate X-ray damage. At temperatures above about 42.5 degrees C hyperthermia results in a qualitatively different lysomal response, probably due to an increased lysosomal membrane permeability. The change is observed immediately after heating and remains high for at least 4 hours. The resultant release of hydrolases into the cytoplasm may be involved in the irreversible cell damage caused by severe hyperthermia."}
{"id": "PMID:224000", "title": "Suppression of induced beta-galactosidase synthesis by cysteamine and its reversion by gamma-irradiation in the presence of ascorbate.", "content": "The induced synthesis of beta-galactosidase in E. coli was found to be inhibited by cysteamine. This inhibitory effect of the SH compound was antagonized by the addition of ascorbate followed by gamma-irradiation with relatively low doses. The cAMP level which, it has been suggested, plays a role in the radioprotective action of cysteamine, is stabilized by ascorbate against changes induced by irradiation.", "contents": "Suppression of induced beta-galactosidase synthesis by cysteamine and its reversion by gamma-irradiation in the presence of ascorbate. The induced synthesis of beta-galactosidase in E. coli was found to be inhibited by cysteamine. This inhibitory effect of the SH compound was antagonized by the addition of ascorbate followed by gamma-irradiation with relatively low doses. The cAMP level which, it has been suggested, plays a role in the radioprotective action of cysteamine, is stabilized by ascorbate against changes induced by irradiation."}
{"id": "PMID:224001", "title": "Enhancement of radiation killing of cultured mammalian cells by cordycepin.", "content": "Asynchronous populations of rat hepatoma cells (H4) in log-phase growth survived a 3-hour exposure to cordycepin (3'-deoxyadenosine), and RNA antimetabolite, in a simple exponential fashion with a 'DO' of 43.8 microM/l. When cordycepin-treated cells were exposed to X-irradiation, the resultant survival levels were much lower than one would expect were the agents simply additive. Patterns of X-ray survival of cells treated with cordycepin were dependent on drug concentration, the predominant effect being to decrease the DO of the X-ray survival curve. The increased sensitivity of cells exposed to cordycepin to subsequent X-ray treatment persists for longer than 4 hours after drug administration. Although immediate cordycepin post-treatment of X-irradiated cells is less effective than pre-treatment, the interaction is still significant. Cordycepin treatment did not appear to reduce split-dose recovery or to inhibit the rejoining of single-strand breaks as measured by DNA sedimentation in alkaline-sucrose gradients.", "contents": "Enhancement of radiation killing of cultured mammalian cells by cordycepin. Asynchronous populations of rat hepatoma cells (H4) in log-phase growth survived a 3-hour exposure to cordycepin (3'-deoxyadenosine), and RNA antimetabolite, in a simple exponential fashion with a 'DO' of 43.8 microM/l. When cordycepin-treated cells were exposed to X-irradiation, the resultant survival levels were much lower than one would expect were the agents simply additive. Patterns of X-ray survival of cells treated with cordycepin were dependent on drug concentration, the predominant effect being to decrease the DO of the X-ray survival curve. The increased sensitivity of cells exposed to cordycepin to subsequent X-ray treatment persists for longer than 4 hours after drug administration. Although immediate cordycepin post-treatment of X-irradiated cells is less effective than pre-treatment, the interaction is still significant. Cordycepin treatment did not appear to reduce split-dose recovery or to inhibit the rejoining of single-strand breaks as measured by DNA sedimentation in alkaline-sucrose gradients."}
{"id": "PMID:224002", "title": "Hydrated electron-initiated main-chain scission in peptides: an e.s.r. and spin-trapping study.", "content": "The reactions of hydrated electrons (eaq-) with 19 tripeptides were investigated. Hydrated electrons were produced by gamma-radiolysis of aqueous peptide solutions containing sufficient sodium formate to remove hydroxyl radicals and hydrogen atoms. t-Butanol was also used to scavenge hydroxyl radicals. The short-lived radicals formed by the reactions of eaq- with the peptides were spin-trapped with t-nitrosobutane to form stable nitroxide radicals and identified by e.s.r. spectroscopy. The tripeptides studied contained two glycine residues. Following the addition of eaq- to tripeptides, C-N bond scission was observed at three sites. Cleavage occurred between the nitrogen of the ammonium group and the alpha-carbon and between the nitrogen of the peptide linkage and the adjoining alpha-carbons. The radicals corresponding to each of these three types of scission were identified. From a comparison of the radical yields of the reaction of eaq- with ala, (ala)2, and poly-DL-ananine with an average degree of polymerization of 1800, it was shown that eaq-, can react with many carbonyl groups of poly-DL-alanine, leading to main-chain scission. Analogous reactions of eaq- with proteins and enzymes may be expected to lead to loss of biological activity.", "contents": "Hydrated electron-initiated main-chain scission in peptides: an e.s.r. and spin-trapping study. The reactions of hydrated electrons (eaq-) with 19 tripeptides were investigated. Hydrated electrons were produced by gamma-radiolysis of aqueous peptide solutions containing sufficient sodium formate to remove hydroxyl radicals and hydrogen atoms. t-Butanol was also used to scavenge hydroxyl radicals. The short-lived radicals formed by the reactions of eaq- with the peptides were spin-trapped with t-nitrosobutane to form stable nitroxide radicals and identified by e.s.r. spectroscopy. The tripeptides studied contained two glycine residues. Following the addition of eaq- to tripeptides, C-N bond scission was observed at three sites. Cleavage occurred between the nitrogen of the ammonium group and the alpha-carbon and between the nitrogen of the peptide linkage and the adjoining alpha-carbons. The radicals corresponding to each of these three types of scission were identified. From a comparison of the radical yields of the reaction of eaq- with ala, (ala)2, and poly-DL-ananine with an average degree of polymerization of 1800, it was shown that eaq-, can react with many carbonyl groups of poly-DL-alanine, leading to main-chain scission. Analogous reactions of eaq- with proteins and enzymes may be expected to lead to loss of biological activity."}
{"id": "PMID:224003", "title": "\"Triple infections\" (fungal, bacterial and viral) in immunosuppressed renal transplant recipients.", "content": "In a period of 5 years, 8 out of 77 renal transplant patients showed simultaneous fungal, bacterial and viral infections. Candida albicans was found in all cases. The most severe bacterial complications were infections with Klebsiella, Pseudomonas and Staphylococcus aureus. Cytomegalovirus, persistent HBsAg positive hepatitis, herpes zoster, and herpes simplex infections were also found. Seven patients died of bacterial superinfection and miliary tuberculosis. The data presented show that \"triple infections\" are associated with high mortality and that miliary tuberculosis occurred frequently in immunosuppressed renal transplant recipients.", "contents": "\"Triple infections\" (fungal, bacterial and viral) in immunosuppressed renal transplant recipients. In a period of 5 years, 8 out of 77 renal transplant patients showed simultaneous fungal, bacterial and viral infections. Candida albicans was found in all cases. The most severe bacterial complications were infections with Klebsiella, Pseudomonas and Staphylococcus aureus. Cytomegalovirus, persistent HBsAg positive hepatitis, herpes zoster, and herpes simplex infections were also found. Seven patients died of bacterial superinfection and miliary tuberculosis. The data presented show that \"triple infections\" are associated with high mortality and that miliary tuberculosis occurred frequently in immunosuppressed renal transplant recipients."}
{"id": "PMID:224004", "title": "Models of electrolyte absorption and secretion by gastrointestinal epithelia.", "content": "An attempt has been made to account for the electrolyte transport properties of several gastrointestinal epithelia in terms of relatively simple cell models. In doing so, it becomes apparent that the complex patterns of electrolyte absorption and secretion by tissues such as in vitro rabbit ileum may actually represent a combination or superposition of several basic transport processes that can be more readily identified in other epithelia. Thus, attempts to explain the effects of agents such as cyclic AMP in terms of a single mechanism of action may prove to be unproductive for such tissues. Clearly, our approach has involved certain speculations and, undoubtedly, oversimplifications. Only those processes which appear to be responsible for sodium and chloride transport have been dealt with in any detail; much remains to be learned about the processes responsible for the absorptive and secretory movements of other ions, principally HCO3. However, this analysis may be useful in bringing a degree of uniformity to a complex area and, hopefully, has identified certain important gaps in our understanding of electrolyte transport at the cellular level which require further investigation.", "contents": "Models of electrolyte absorption and secretion by gastrointestinal epithelia. An attempt has been made to account for the electrolyte transport properties of several gastrointestinal epithelia in terms of relatively simple cell models. In doing so, it becomes apparent that the complex patterns of electrolyte absorption and secretion by tissues such as in vitro rabbit ileum may actually represent a combination or superposition of several basic transport processes that can be more readily identified in other epithelia. Thus, attempts to explain the effects of agents such as cyclic AMP in terms of a single mechanism of action may prove to be unproductive for such tissues. Clearly, our approach has involved certain speculations and, undoubtedly, oversimplifications. Only those processes which appear to be responsible for sodium and chloride transport have been dealt with in any detail; much remains to be learned about the processes responsible for the absorptive and secretory movements of other ions, principally HCO3. However, this analysis may be useful in bringing a degree of uniformity to a complex area and, hopefully, has identified certain important gaps in our understanding of electrolyte transport at the cellular level which require further investigation."}
{"id": "PMID:224007", "title": "[Bronchiolo-alveolar cell carcinoma].", "content": "15 cases of bronchiolo-alveolar cell carcinoma were observed at the Dept. of Surgery of the University Hospital of Zurich from 1961 to 1976. The mean age of these patients was 56 years. The sex distribution was 13 males and 2 females. Five cases were discovered accidentally; the symptoms of the remaining 10 were uncharacteristic. Cytology, bronchoscopy and mediastinoscopy were negative at early stages. Diagnosis was made by histologic examination of the specimens only. Needle biopsy, performed routinely over recent years, proved helpful in 4 cases. In 12 out of 14 patients, lobectomy was considered 'radical'; nevertheless, only 2 survived more than 5 years. The disseminated form of the bronchiolo-alveolar cell carcinoma is characterized by a particularly poor prognosis. According to our experience and to the literature, only the solitary, nodular type shows a more favourable outlook.", "contents": "[Bronchiolo-alveolar cell carcinoma]. 15 cases of bronchiolo-alveolar cell carcinoma were observed at the Dept. of Surgery of the University Hospital of Zurich from 1961 to 1976. The mean age of these patients was 56 years. The sex distribution was 13 males and 2 females. Five cases were discovered accidentally; the symptoms of the remaining 10 were uncharacteristic. Cytology, bronchoscopy and mediastinoscopy were negative at early stages. Diagnosis was made by histologic examination of the specimens only. Needle biopsy, performed routinely over recent years, proved helpful in 4 cases. In 12 out of 14 patients, lobectomy was considered 'radical'; nevertheless, only 2 survived more than 5 years. The disseminated form of the bronchiolo-alveolar cell carcinoma is characterized by a particularly poor prognosis. According to our experience and to the literature, only the solitary, nodular type shows a more favourable outlook."}
{"id": "PMID:224008", "title": "Use of protein A-coated colloidal gold particles for immunoelectronmicroscopic localization of ACTH on ultrathin sections.", "content": "ACTH was localized in dissociated porcine adenohypophysial cells using a novel indirect EM immunocytochemical technique. Incubation of ultrathin resin sections in anti-ACTH was followed by incubation with protein A-coated colloidal gold particles. Protein A binds specifically to the Fc part of the IgG molecule, and thus the ACTH-containing secretory granules became labelled with electron-dense gold particles. With this method, the dissociated porcine ACTH cells was identified as containing numerous round or ovoid 170--300 nm secretory granules.", "contents": "Use of protein A-coated colloidal gold particles for immunoelectronmicroscopic localization of ACTH on ultrathin sections. ACTH was localized in dissociated porcine adenohypophysial cells using a novel indirect EM immunocytochemical technique. Incubation of ultrathin resin sections in anti-ACTH was followed by incubation with protein A-coated colloidal gold particles. Protein A binds specifically to the Fc part of the IgG molecule, and thus the ACTH-containing secretory granules became labelled with electron-dense gold particles. With this method, the dissociated porcine ACTH cells was identified as containing numerous round or ovoid 170--300 nm secretory granules."}
{"id": "PMID:224009", "title": "Ultrahistochemical investigations of dog lung surfactant with ruthenium red and iodoplatinate reactions.", "content": "Dog lungs have been fixed by immersion and submitted to two histochemical procedures. An iodoplatinate reaction technique to demontrate choline phospholipids stains cell membranes, inclusion bodies of type II alveolar epithelial cells and tubular myelin figures of pulmonary surfactant, the latter as electron-dense lines measuring 5 nm. The ruthenium red procedure gives rise to an intense contrast of the free surface of alveolar epithelium. The 5 nm-lines of the pulmonary surfactant are seen as electron-lucent lines, but bordered by electron-dense rims. Though both techniques have limitations in their interpretation, which are discussed in this paper, they demonstrate the tubular myelin figures to be a highly organized mixture of phospholipids and glycoproteins.", "contents": "Ultrahistochemical investigations of dog lung surfactant with ruthenium red and iodoplatinate reactions. Dog lungs have been fixed by immersion and submitted to two histochemical procedures. An iodoplatinate reaction technique to demontrate choline phospholipids stains cell membranes, inclusion bodies of type II alveolar epithelial cells and tubular myelin figures of pulmonary surfactant, the latter as electron-dense lines measuring 5 nm. The ruthenium red procedure gives rise to an intense contrast of the free surface of alveolar epithelium. The 5 nm-lines of the pulmonary surfactant are seen as electron-lucent lines, but bordered by electron-dense rims. Though both techniques have limitations in their interpretation, which are discussed in this paper, they demonstrate the tubular myelin figures to be a highly organized mixture of phospholipids and glycoproteins."}
{"id": "PMID:224010", "title": "Experimental canine anaphylaxis: cyclic nucleotides, histamine, and lung function.", "content": "We studied the effects of Ascaris suum antigen (iv) in 32 natively allergic, anesthetized dogs. After thoracotomy, bilateral cervical vagotomy, and propranolol, samples of peripheral lung frozen in situ were obtained for measurement of cyclic nucleotides and histamine. Following Ascaris, lung histamine decreased 20.4 +/- 3.7% (mean +/- SE), cAMP increased 391 +/- 122%, and cGMP increased 110 +/- 20% with increased plasma histamine and physiological changes of anaphylaxis. No significant changes occurred in 10 control dogs. Release of histamine, reflecting immunological degranulation of mast cells, correlated closely with the physiological effects of anaphylaxis. beta-Adrenergic stimulation with isoproterenol prevented these physiological effects of anaphylaxis in three dogs studied. Furthermore, the level of cAMP induced in lung tissue by beta-adrenergic stimulation in these dogs correlated with the degree of inhibition of immunologically induced histamine release. These results illustrate the suitability of this experimental preparation to study the biochemical and physiological mechanisms of anaphylaxis in vivo.", "contents": "Experimental canine anaphylaxis: cyclic nucleotides, histamine, and lung function. We studied the effects of Ascaris suum antigen (iv) in 32 natively allergic, anesthetized dogs. After thoracotomy, bilateral cervical vagotomy, and propranolol, samples of peripheral lung frozen in situ were obtained for measurement of cyclic nucleotides and histamine. Following Ascaris, lung histamine decreased 20.4 +/- 3.7% (mean +/- SE), cAMP increased 391 +/- 122%, and cGMP increased 110 +/- 20% with increased plasma histamine and physiological changes of anaphylaxis. No significant changes occurred in 10 control dogs. Release of histamine, reflecting immunological degranulation of mast cells, correlated closely with the physiological effects of anaphylaxis. beta-Adrenergic stimulation with isoproterenol prevented these physiological effects of anaphylaxis in three dogs studied. Furthermore, the level of cAMP induced in lung tissue by beta-adrenergic stimulation in these dogs correlated with the degree of inhibition of immunologically induced histamine release. These results illustrate the suitability of this experimental preparation to study the biochemical and physiological mechanisms of anaphylaxis in vivo."}
{"id": "PMID:224011", "title": "Factors affecting the physical performance of the rat in hyperbaric environments.", "content": "Experiments were designed to partition the effect of inspired oxygen tension (PIO2), gas density (rho), and ambient pressure (P) at rest and during exercise in rats. At rest oxygen uptake (VO2) was reduced by 19.5% (P less than 0.01) in 3 ATA air and by 32.1% (P less than 0.01) in 10 ATA air from 1 ATA air control of 29.3 +/- 1.21 (SE) ml/min.kg; there was no difference in VO2 between 1, 3, and 10 ATA He mixtures containing 20% O2. During exercise, VO2 was depressed by 36.2% (P less than 0.01) in 3 ATA air from 1 ATA air value of 55.3 +/- 3.23 ml/min.kg; VO2 was unaffected in 3 ATA He containing 20% O2 as compared to that of 46.5 +/- 2.43 ml/min.kg at 1 ATA He-O2 ambient. These VO2 values were compared to that obtained from normoxic ambients for separation of effects of elevated PIO2, P, and rho on VO2 at rest and during exercise. The effect of PIO2 was deduced by comparing VO2 in normoxic and hyperoxic He and N2 at a given P and rho. The density effect was obtained by comparing the VO2 in various densities at a given P and PIO2. The P effect was obtained by comparing the VO2 in various ambient pressures at a given rho and PIO2. Summation of the effects of P, rho, and PIO2 sufficiently approximates the changes in VO2 at rest. The same procedure underestimates the actually measured VO2 in all N2 ambients.", "contents": "Factors affecting the physical performance of the rat in hyperbaric environments. Experiments were designed to partition the effect of inspired oxygen tension (PIO2), gas density (rho), and ambient pressure (P) at rest and during exercise in rats. At rest oxygen uptake (VO2) was reduced by 19.5% (P less than 0.01) in 3 ATA air and by 32.1% (P less than 0.01) in 10 ATA air from 1 ATA air control of 29.3 +/- 1.21 (SE) ml/min.kg; there was no difference in VO2 between 1, 3, and 10 ATA He mixtures containing 20% O2. During exercise, VO2 was depressed by 36.2% (P less than 0.01) in 3 ATA air from 1 ATA air value of 55.3 +/- 3.23 ml/min.kg; VO2 was unaffected in 3 ATA He containing 20% O2 as compared to that of 46.5 +/- 2.43 ml/min.kg at 1 ATA He-O2 ambient. These VO2 values were compared to that obtained from normoxic ambients for separation of effects of elevated PIO2, P, and rho on VO2 at rest and during exercise. The effect of PIO2 was deduced by comparing VO2 in normoxic and hyperoxic He and N2 at a given P and rho. The density effect was obtained by comparing the VO2 in various densities at a given P and PIO2. The P effect was obtained by comparing the VO2 in various ambient pressures at a given rho and PIO2. Summation of the effects of P, rho, and PIO2 sufficiently approximates the changes in VO2 at rest. The same procedure underestimates the actually measured VO2 in all N2 ambients."}
{"id": "PMID:224012", "title": "Maturation of ventilation and ventilatory pattern in normal sleeping infants.", "content": "Noninvasive studies of ventilation and ventilatory pattern were performed serially in 15 normal infants in the first 4 mo of life during REM and quiet sleep with the barometric method. We measured tidal volume (VT), total respiratory cycle time (Ttot), inspiratory time (Ti), expiratory time (TE), mean inspiratory flow (VT/TI), and respiratory \"duty cycle\" (TI/Ttot). Vt, Ttot, TI, TE, VT/TI, and VT/Ttot but not TI/Ttot increased with age. In all age groups, Ttot, TI, and TE but not VT/TI were greater in quiet than in REM sleep. In the first 2 mo of life, VT was greater in quiet than in REM sleep; in the older infants, VT/Ttot was smaller in quiet than in REM sleep. TI/Ttot was not dependent on sleep state. Thus, because VT/Ttot = VT/TI X TI/Ttot, the increase in VT/Ttot with age results from an increase in mean inspiratory flow rather than from changes in respiratory \"duty cycle\". Further, the \"on-switching\" as well as the \"off-switching\" of inspiratory activity depends on sleep state.", "contents": "Maturation of ventilation and ventilatory pattern in normal sleeping infants. Noninvasive studies of ventilation and ventilatory pattern were performed serially in 15 normal infants in the first 4 mo of life during REM and quiet sleep with the barometric method. We measured tidal volume (VT), total respiratory cycle time (Ttot), inspiratory time (Ti), expiratory time (TE), mean inspiratory flow (VT/TI), and respiratory \"duty cycle\" (TI/Ttot). Vt, Ttot, TI, TE, VT/TI, and VT/Ttot but not TI/Ttot increased with age. In all age groups, Ttot, TI, and TE but not VT/TI were greater in quiet than in REM sleep. In the first 2 mo of life, VT was greater in quiet than in REM sleep; in the older infants, VT/Ttot was smaller in quiet than in REM sleep. TI/Ttot was not dependent on sleep state. Thus, because VT/Ttot = VT/TI X TI/Ttot, the increase in VT/Ttot with age results from an increase in mean inspiratory flow rather than from changes in respiratory \"duty cycle\". Further, the \"on-switching\" as well as the \"off-switching\" of inspiratory activity depends on sleep state."}
{"id": "PMID:224013", "title": "Oxygen extraction by canine hindlimb during hypoxic hypoxia.", "content": "Regional and total blood flow and O2 uptake (VO2) were measured in 10 anesthetized paralyzed dogs in which venous outflow from the left hindlimb (less paw) was directed through the femoral vein. After being ventilated on room air during a 40-min control period, they were ventilated on 12.0% O2 for 40 min, 9.2% O2 for 40 min, and again on room air for 40 min. A second group of 10 was treated the same after they were given 1.0 mg/kg propranolol to block beta-adrenergic receptors. Neither limb blood flow nor cardiac output changed significantly during moderate hypoxia in either group; both increased in severe hypoxia but only in the no-beta-block group. Limb VO2 was not decreased significantly in either group during moderate hypoxia but total VO2 was decreased in the beta-block group. Total VO2 was decreased in both groups during severe hypoxia but limb VO2 was maintained in the beta-block group. beta-Block prevented the fall in total and limb peripheral resistance seen in severe hypoxia but did not alter the consistently more efficient utilization of total O2 delivery shown by the limb in comparison to the whole body by higher O2 extraction ratios and lower venous O2 pressure. beta-Vasodilator receptors evidently played an active part in the vasodilatation seen during severe hypoxia.", "contents": "Oxygen extraction by canine hindlimb during hypoxic hypoxia. Regional and total blood flow and O2 uptake (VO2) were measured in 10 anesthetized paralyzed dogs in which venous outflow from the left hindlimb (less paw) was directed through the femoral vein. After being ventilated on room air during a 40-min control period, they were ventilated on 12.0% O2 for 40 min, 9.2% O2 for 40 min, and again on room air for 40 min. A second group of 10 was treated the same after they were given 1.0 mg/kg propranolol to block beta-adrenergic receptors. Neither limb blood flow nor cardiac output changed significantly during moderate hypoxia in either group; both increased in severe hypoxia but only in the no-beta-block group. Limb VO2 was not decreased significantly in either group during moderate hypoxia but total VO2 was decreased in the beta-block group. Total VO2 was decreased in both groups during severe hypoxia but limb VO2 was maintained in the beta-block group. beta-Block prevented the fall in total and limb peripheral resistance seen in severe hypoxia but did not alter the consistently more efficient utilization of total O2 delivery shown by the limb in comparison to the whole body by higher O2 extraction ratios and lower venous O2 pressure. beta-Vasodilator receptors evidently played an active part in the vasodilatation seen during severe hypoxia."}
{"id": "PMID:224015", "title": "Reduced lung volume during behavioral active sleep in the newborn.", "content": "In a previous study of newborn infants we observed overall rib cage collapse during active sleep and postulated that the lungs also could be deflated, leading to reduced oxygen stores and circumstances favoring the rapid development of hypoxemia during apnea. In this study, thoracic gas volume (TGV) has been measured directly by occlusion plethysmography in six normal babies during behavioral quiet and active sleep and related to the different movements of the rib cage and abdomen-diaphragm that occur during each sleep state. TGV was significantly reduced in each baby during active sleep and was associated with rib cage deflation and increased abdomen-diaphragm excursions. The average reduction of TGV was 31% when compared with the volume in quiet sleep and did not depend on the order in which the sleep states were tested. The reduced lung volume in active sleep could have implications for the regulation of breathing in that state. A reduction of lung oxygen stores in active sleep suggests an age-related vulnerability of the young infant to hypoxemia.", "contents": "Reduced lung volume during behavioral active sleep in the newborn. In a previous study of newborn infants we observed overall rib cage collapse during active sleep and postulated that the lungs also could be deflated, leading to reduced oxygen stores and circumstances favoring the rapid development of hypoxemia during apnea. In this study, thoracic gas volume (TGV) has been measured directly by occlusion plethysmography in six normal babies during behavioral quiet and active sleep and related to the different movements of the rib cage and abdomen-diaphragm that occur during each sleep state. TGV was significantly reduced in each baby during active sleep and was associated with rib cage deflation and increased abdomen-diaphragm excursions. The average reduction of TGV was 31% when compared with the volume in quiet sleep and did not depend on the order in which the sleep states were tested. The reduced lung volume in active sleep could have implications for the regulation of breathing in that state. A reduction of lung oxygen stores in active sleep suggests an age-related vulnerability of the young infant to hypoxemia."}
{"id": "PMID:224016", "title": "Inert gas transport in the microcirculation: risk of isobaric supersaturation.", "content": "This paper is concerned with the theretical background and implications of isobaric supersaturation and bubble formation in the microcirculation following an abrupt shift from one inspired inert gas to another. The use of more than one inert gas, simultaneously or sequentially, has become common in diving and presents risks as well as potential benefits. A review of microcirculatory model useds, theoretical approaches to decompression, and order of magnitude calculations indicates that present empiricisms are inadequate for predicting such supersaturation phenomena. This is true whether based on the familiar assumption of perfusion-limited behavior or its diffusion-limited counterpart. The \"chromatographic\"  model used here, which considers both perfusion and axial diffusion in tissue cylinders, shows that these combined effects can produce unexpectedly high local supersaturation. The implications include new possibilities for the experimental evaluation of gas transport models as well as practical risks of inert gas shifts in diving and certain diagnostic procedures.", "contents": "Inert gas transport in the microcirculation: risk of isobaric supersaturation. This paper is concerned with the theretical background and implications of isobaric supersaturation and bubble formation in the microcirculation following an abrupt shift from one inspired inert gas to another. The use of more than one inert gas, simultaneously or sequentially, has become common in diving and presents risks as well as potential benefits. A review of microcirculatory model useds, theoretical approaches to decompression, and order of magnitude calculations indicates that present empiricisms are inadequate for predicting such supersaturation phenomena. This is true whether based on the familiar assumption of perfusion-limited behavior or its diffusion-limited counterpart. The \"chromatographic\"  model used here, which considers both perfusion and axial diffusion in tissue cylinders, shows that these combined effects can produce unexpectedly high local supersaturation. The implications include new possibilities for the experimental evaluation of gas transport models as well as practical risks of inert gas shifts in diving and certain diagnostic procedures."}
{"id": "PMID:224017", "title": "Solubility and partition coefficients for gases in rabbit brain and blood.", "content": "Solubility and partition coefficients for argon, methane, neon, nitrogen, and sulfur hexafluoride in normal saline, rabbit blood, and exsanguinated rabbit brain were determined in a two-step process that involved equilibration of the various aliquots, and subsequent analysis by gas chromatography. Brain-blood partition coefficient was specifically higher than one for argon, neon, and sulfur hexafluoride, and questionably significant (P less than 0.025) for nitrogen.", "contents": "Solubility and partition coefficients for gases in rabbit brain and blood. Solubility and partition coefficients for argon, methane, neon, nitrogen, and sulfur hexafluoride in normal saline, rabbit blood, and exsanguinated rabbit brain were determined in a two-step process that involved equilibration of the various aliquots, and subsequent analysis by gas chromatography. Brain-blood partition coefficient was specifically higher than one for argon, neon, and sulfur hexafluoride, and questionably significant (P less than 0.025) for nitrogen."}
{"id": "PMID:224018", "title": "Solubility of inert gases in homogenates of canine lung tissue.", "content": "The solubility of sulfur hexafluoride (SF6), ethane, cyclopropane, halothane, diethyl ether, and acetone in homogenates of dog lung tissue were measured and compared with values obtained in dog blood. The measurements were made to provide data for a method for determining distribution of ventilation, blood flow, and tissue volume (Physiologist 20: 95, 1977) and for reasons discussed, the blood was not washed from the tissue prior to homogenization. All gases except SF6 were significantly more soluble in blood than  lung tissue, whereas SF6 was 3.7 times more soluble in tissue than blood. It was further found that SF6 is 5 times more soluble, and ethane is twice as soluble in tissue obtained from lungs containing blood than in tissue obtained from rinsed lungs, suggesting that measurements of parenchymal solubility made on tissue from sinsed lungs may be considerably in error for some lipid-soluble gases.", "contents": "Solubility of inert gases in homogenates of canine lung tissue. The solubility of sulfur hexafluoride (SF6), ethane, cyclopropane, halothane, diethyl ether, and acetone in homogenates of dog lung tissue were measured and compared with values obtained in dog blood. The measurements were made to provide data for a method for determining distribution of ventilation, blood flow, and tissue volume (Physiologist 20: 95, 1977) and for reasons discussed, the blood was not washed from the tissue prior to homogenization. All gases except SF6 were significantly more soluble in blood than  lung tissue, whereas SF6 was 3.7 times more soluble in tissue than blood. It was further found that SF6 is 5 times more soluble, and ethane is twice as soluble in tissue obtained from lungs containing blood than in tissue obtained from rinsed lungs, suggesting that measurements of parenchymal solubility made on tissue from sinsed lungs may be considerably in error for some lipid-soluble gases."}
{"id": "PMID:224019", "title": "Arousal, ventilatory, and airway responses to bronchopulmonary stimulation in sleeping dogs.", "content": "We studied waking, ventilatory, and reflex tracheal smooth muscle (TSM) responses to tracheobronchial irritation or lung inflation in three sleeping dogs. The dogs breathed through a cuffed endotracheal tube, and airflow was measured with a pneumotachograph. TSM tone was monitored directly by measuring pressure in the water-filled cuff of the endotracheal tube. Mild degrees of tracheobronchia irritation, produced by squirting 0.1--1.0 ml of water into the lower trachea, or by having the dogs inhale one breath of acetic acid vapor (concentration 17 ppm), generally caused arousal from slow-wave sleep (SWS), but not from rapid-eye-movement (REM) sleep. During wakefulness the irritant stimuli caused coughing and TSM constriction; during SWS or REM sleep, these responses occurred only if the stimulus first produced arousal. In contrast, stimulation of pulmonary stretch receptors by lung inflation did not cause arousal, but readily produced apnea and TSM relaxation during SWS. The results indicate that cough and airway smooth muscle constriction in response to bronchopulmonary irritant stimuli do not occur in the absence of arousal, and that arousal responses to such stimuli are depressed in REM sleep.", "contents": "Arousal, ventilatory, and airway responses to bronchopulmonary stimulation in sleeping dogs. We studied waking, ventilatory, and reflex tracheal smooth muscle (TSM) responses to tracheobronchial irritation or lung inflation in three sleeping dogs. The dogs breathed through a cuffed endotracheal tube, and airflow was measured with a pneumotachograph. TSM tone was monitored directly by measuring pressure in the water-filled cuff of the endotracheal tube. Mild degrees of tracheobronchia irritation, produced by squirting 0.1--1.0 ml of water into the lower trachea, or by having the dogs inhale one breath of acetic acid vapor (concentration 17 ppm), generally caused arousal from slow-wave sleep (SWS), but not from rapid-eye-movement (REM) sleep. During wakefulness the irritant stimuli caused coughing and TSM constriction; during SWS or REM sleep, these responses occurred only if the stimulus first produced arousal. In contrast, stimulation of pulmonary stretch receptors by lung inflation did not cause arousal, but readily produced apnea and TSM relaxation during SWS. The results indicate that cough and airway smooth muscle constriction in response to bronchopulmonary irritant stimuli do not occur in the absence of arousal, and that arousal responses to such stimuli are depressed in REM sleep."}
{"id": "PMID:224020", "title": "Exhaustive exercise, endurance training, and acid hydrolase activity in skeletal muscle.", "content": "The activity of eight acid hydrolases and two energy metabolism enzymes were assayed from homogenates of predominantly red (proximal heads of m. vastus lateralis, m. vastus medialis, and m. vastus intermedius) and predominantly white (distal head of m. vastus lateralis) skeletal muscle of mice belonging to one of the following groups: 1) sedentary controls, never trained or exhausted; 2) exhausted controls, exhausted once by running on a treadmill 5, 10, or 20 days before killing; 3) trained mice, exercising until killed; 4) exhausted trained mice, exercising until exhausted 5, 10 or 20 days before killing, not exercising during that period; and 5) detrained mice, terminating training 5, 10, or 20 days before killing. In untrained but not in trained animals, exhaustive exercise caused, 5 days afterward, fiber necrosis and a marked increase in the activities of beta-glucuronidase, beta-N-acetylglucosaminidase, arylsulphatase, ribonuclease, deoxyribonuclease, cathepsin D, and cathepsin C, especially in red muscle fibers. Training increased the activities of citrate synthase, beta-glucuronidase, and cathepsin D in both muscle types and those of beta-N-acetylglucosaminidase, arylsulphatase, and cathepsin C in red muscle. Effects of detraining were minor. Exhaustive exercise causes lethal and evidently also sublethal fiber injuries manifesting themselves as an activation of the lysosomal system of muscle fibers 5 days later. Training affects cellular homeostasis by causing an apparent resistance to the damaging effects of exhaustive exercise. Moderately increased hydrolase activities may reflect increased turnover in endurance-trained muscles.", "contents": "Exhaustive exercise, endurance training, and acid hydrolase activity in skeletal muscle. The activity of eight acid hydrolases and two energy metabolism enzymes were assayed from homogenates of predominantly red (proximal heads of m. vastus lateralis, m. vastus medialis, and m. vastus intermedius) and predominantly white (distal head of m. vastus lateralis) skeletal muscle of mice belonging to one of the following groups: 1) sedentary controls, never trained or exhausted; 2) exhausted controls, exhausted once by running on a treadmill 5, 10, or 20 days before killing; 3) trained mice, exercising until killed; 4) exhausted trained mice, exercising until exhausted 5, 10 or 20 days before killing, not exercising during that period; and 5) detrained mice, terminating training 5, 10, or 20 days before killing. In untrained but not in trained animals, exhaustive exercise caused, 5 days afterward, fiber necrosis and a marked increase in the activities of beta-glucuronidase, beta-N-acetylglucosaminidase, arylsulphatase, ribonuclease, deoxyribonuclease, cathepsin D, and cathepsin C, especially in red muscle fibers. Training increased the activities of citrate synthase, beta-glucuronidase, and cathepsin D in both muscle types and those of beta-N-acetylglucosaminidase, arylsulphatase, and cathepsin C in red muscle. Effects of detraining were minor. Exhaustive exercise causes lethal and evidently also sublethal fiber injuries manifesting themselves as an activation of the lysosomal system of muscle fibers 5 days later. Training affects cellular homeostasis by causing an apparent resistance to the damaging effects of exhaustive exercise. Moderately increased hydrolase activities may reflect increased turnover in endurance-trained muscles."}
{"id": "PMID:224021", "title": "Effects of high oxygen exposure on bioenergetics in isolated type II pneumocytes.", "content": "O2-mediated alterations in cell energy metabolism may play a role in structural and functional abnormalities described in type II pneumocytes (T-II-P) following in vivo hyperoxia. Bioenergetic alterations produced by hyperoxia (95% O2) were therefore examined in a culture-maintained cell line derived from T-II-P. Exposure of cell monolayers to 95% O2 for 96 h results in a significant decrease in O2 consumption (from 0.52 +/- 0.07 to 0.30 +/- 0.08, P less than 0.01), suggesting impaired mitochondrial energy provision. In addition, there are increased rates of aerobic lactate production (from 2.89 +/- 0.52 to 3.84 +/-0.80, P less than 0.05) with loss of Pasteur effect, indicating a shift to glycolytic metabolism at relatively high PO2's. These metabolic changes are not accompanied by altered activities of critical mitochondrial (cytochrome oxidase) or glycolytic (pyruvate kinase, phosphofructokinase) enzymes. Altered cell bioenergetics following hyperoxia may this represent an important secondary mechanism leading to functional abnormalities in T-II-P.", "contents": "Effects of high oxygen exposure on bioenergetics in isolated type II pneumocytes. O2-mediated alterations in cell energy metabolism may play a role in structural and functional abnormalities described in type II pneumocytes (T-II-P) following in vivo hyperoxia. Bioenergetic alterations produced by hyperoxia (95% O2) were therefore examined in a culture-maintained cell line derived from T-II-P. Exposure of cell monolayers to 95% O2 for 96 h results in a significant decrease in O2 consumption (from 0.52 +/- 0.07 to 0.30 +/- 0.08, P less than 0.01), suggesting impaired mitochondrial energy provision. In addition, there are increased rates of aerobic lactate production (from 2.89 +/- 0.52 to 3.84 +/-0.80, P less than 0.05) with loss of Pasteur effect, indicating a shift to glycolytic metabolism at relatively high PO2's. These metabolic changes are not accompanied by altered activities of critical mitochondrial (cytochrome oxidase) or glycolytic (pyruvate kinase, phosphofructokinase) enzymes. Altered cell bioenergetics following hyperoxia may this represent an important secondary mechanism leading to functional abnormalities in T-II-P."}
{"id": "PMID:224022", "title": "Diaphragmatic muscle tone.", "content": "It is generally believed that there is a scarcity of muscle spindles in the diaphragm and that there is no tonic activity at end expiration. This conclusion is based mainly on animal studies and the difficulty in differentiating tonic electromyogram activity from noise. We have, however, found a number of muscle spindles in the newborn human diagphragm, concentrated in the region of the central tendon. We also tried to detect tonic activity by decreasing it (by rapid-eye movement (REM) sleep or anesthesia) or increasing it (with abdominal loading). During REM sleep in five infants and five adults, using subcostal electrodes were observed a marked fall in tonic activity (P less than 0.001) compared to non-REM or quiet sleep. We also observed a reduction in diaphragmatic tonic activity with halothane anesthesia (P less than 0.001). With esophageal electrodes in adult subjects, there was a rise in tonic diaphragmatic activity proportional to the amount of abdomina load (P less than 0.001). We conclude that there are muscle spindles in the human diaphragm and that there is tonic activity at end expiration.", "contents": "Diaphragmatic muscle tone. It is generally believed that there is a scarcity of muscle spindles in the diaphragm and that there is no tonic activity at end expiration. This conclusion is based mainly on animal studies and the difficulty in differentiating tonic electromyogram activity from noise. We have, however, found a number of muscle spindles in the newborn human diagphragm, concentrated in the region of the central tendon. We also tried to detect tonic activity by decreasing it (by rapid-eye movement (REM) sleep or anesthesia) or increasing it (with abdominal loading). During REM sleep in five infants and five adults, using subcostal electrodes were observed a marked fall in tonic activity (P less than 0.001) compared to non-REM or quiet sleep. We also observed a reduction in diaphragmatic tonic activity with halothane anesthesia (P less than 0.001). With esophageal electrodes in adult subjects, there was a rise in tonic diaphragmatic activity proportional to the amount of abdomina load (P less than 0.001). We conclude that there are muscle spindles in the human diaphragm and that there is tonic activity at end expiration."}
{"id": "PMID:224023", "title": "Dibutyryl cyclic GMP and hyperventilation promote rat lung phospholipid release.", "content": "Ventilation of rats at high inspiratory pressures raises lung tissue content of guanosine 3',5'-cyclic monophosphate (cGMP). Hyperventilation in rabbits augments release of phospholipid into lavage fluid. Can cGMP, in the absence of hyperventilation, increase lung phospholipid release? Sprague-Dawley rats are injected with [14C]palmitate, and after 1.5 h are anesthetized and ventilated for 20 min. Three groups are ventilated at peak inspiratory pressures (PIP) of 10 cmH2O, while saline, dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP), or dibutyryl cGMP (DBcGMP) is infused into the pulmonary artery. In a fourth group, saline is infused into the pulmonary artery, but ventilation is performed with PIP of 25 cmH2O. Lung tissue and lavage fluid are then analyzed for phospholipid (PL) content and for incorporation of [14C]palmitate into lavage and tissue PL fractions. Ventilation at increased pressure and infusion of DBcGMP are associated with increases in release of labeled PL into lavage fraction. The findings suggest that the increase in lavage PL release associated with hyperventilation is, at least in part, mediated by cGMP.", "contents": "Dibutyryl cyclic GMP and hyperventilation promote rat lung phospholipid release. Ventilation of rats at high inspiratory pressures raises lung tissue content of guanosine 3',5'-cyclic monophosphate (cGMP). Hyperventilation in rabbits augments release of phospholipid into lavage fluid. Can cGMP, in the absence of hyperventilation, increase lung phospholipid release? Sprague-Dawley rats are injected with [14C]palmitate, and after 1.5 h are anesthetized and ventilated for 20 min. Three groups are ventilated at peak inspiratory pressures (PIP) of 10 cmH2O, while saline, dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP), or dibutyryl cGMP (DBcGMP) is infused into the pulmonary artery. In a fourth group, saline is infused into the pulmonary artery, but ventilation is performed with PIP of 25 cmH2O. Lung tissue and lavage fluid are then analyzed for phospholipid (PL) content and for incorporation of [14C]palmitate into lavage and tissue PL fractions. Ventilation at increased pressure and infusion of DBcGMP are associated with increases in release of labeled PL into lavage fraction. The findings suggest that the increase in lavage PL release associated with hyperventilation is, at least in part, mediated by cGMP."}
{"id": "PMID:224024", "title": "Pulmonary interdependence of gas transport.", "content": "We have examined the interaction of convection and gas-phase diffusion among parallel pathways of the human lung by solving the differential equation for gas transport in a solid geometric model. Two trumpet-shaped units with a threefold differences in volume flow were joined at a branch point that could be varied in position along the airway tree. Because diffusion dominates gas transport in peripheral airways, or when time for diffusion is large, alveolar concentrations are more homogeneous than predicted from volume flows when the branch point is peripheral to respiratory bronchioles, or when total flow rate is small. When the branch point is in the larger airways, subtending large units of lung, diffusion is less important, so that alveolar concentration of each unit depends almost completely on its volume flow. These simulations provide a possible explanation for experimental findings of partial separation of inert gases of differing diffusivities and of improved O2 exchange when dense gases are breathed.", "contents": "Pulmonary interdependence of gas transport. We have examined the interaction of convection and gas-phase diffusion among parallel pathways of the human lung by solving the differential equation for gas transport in a solid geometric model. Two trumpet-shaped units with a threefold differences in volume flow were joined at a branch point that could be varied in position along the airway tree. Because diffusion dominates gas transport in peripheral airways, or when time for diffusion is large, alveolar concentrations are more homogeneous than predicted from volume flows when the branch point is peripheral to respiratory bronchioles, or when total flow rate is small. When the branch point is in the larger airways, subtending large units of lung, diffusion is less important, so that alveolar concentration of each unit depends almost completely on its volume flow. These simulations provide a possible explanation for experimental findings of partial separation of inert gases of differing diffusivities and of improved O2 exchange when dense gases are breathed."}
{"id": "PMID:224025", "title": "The ultrastructure of the epithelium of the ducts of the Harderian and lacrimal glands of the turkey, fowl and duck.", "content": "The ultrastructure of the epithelium in the Harderian and lacrimal gland ducts of the turkey, fowl and duck has been investigated. The findings establish that the ducts are fundamentally similar in morphology, although species differences occur. The duct epithelia are composed of cuboidal, columnar or pseudostratisfied columnar cells with many secretory vesicles as well as goblet cells. PAS-positive fibrillary rods and crystalline inclusions occupied the cisternae of the rough endoplasmic reticulum of the epithelial cells of turkeys. The crystals, which were thought to evolve from the rods, had a mean periodicity of 7.0 nm. In chicks between 1 and 3 days of age, but not in poults and ducklings, the duct epithelia displayed large intracytoplasmic deposits of glycogen which disappeared by the seventh day.", "contents": "The ultrastructure of the epithelium of the ducts of the Harderian and lacrimal glands of the turkey, fowl and duck. The ultrastructure of the epithelium in the Harderian and lacrimal gland ducts of the turkey, fowl and duck has been investigated. The findings establish that the ducts are fundamentally similar in morphology, although species differences occur. The duct epithelia are composed of cuboidal, columnar or pseudostratisfied columnar cells with many secretory vesicles as well as goblet cells. PAS-positive fibrillary rods and crystalline inclusions occupied the cisternae of the rough endoplasmic reticulum of the epithelial cells of turkeys. The crystals, which were thought to evolve from the rods, had a mean periodicity of 7.0 nm. In chicks between 1 and 3 days of age, but not in poults and ducklings, the duct epithelia displayed large intracytoplasmic deposits of glycogen which disappeared by the seventh day."}
{"id": "PMID:224026", "title": "Morphological and cytochemical study of a hypothalamochiasmatic perivascular neuronal system.", "content": "The topographical localization and some cytochemical characteristics of groups of perivascular neurons in the hypothalamus and in the optic chiasma have been studied. In the anterior hypothalamic area there are neuronal groups located around the blood vessels which penetrate the optic chiasma still associated with neurons. These perivascular neurons show some characteristics similar to those observed in neurosecretory hypothalamic neurons, but differ from them in that they show a greater intensity of thiaminopyrophosphatase and nucleoside-diphosphataseactivities. It is suggested that these neuronal groups may constitute a special hypothalamochiasmatic-perviscular-neurosecretory system (H. Ch. P. N. S.).", "contents": "Morphological and cytochemical study of a hypothalamochiasmatic perivascular neuronal system. The topographical localization and some cytochemical characteristics of groups of perivascular neurons in the hypothalamus and in the optic chiasma have been studied. In the anterior hypothalamic area there are neuronal groups located around the blood vessels which penetrate the optic chiasma still associated with neurons. These perivascular neurons show some characteristics similar to those observed in neurosecretory hypothalamic neurons, but differ from them in that they show a greater intensity of thiaminopyrophosphatase and nucleoside-diphosphataseactivities. It is suggested that these neuronal groups may constitute a special hypothalamochiasmatic-perviscular-neurosecretory system (H. Ch. P. N. S.)."}
{"id": "PMID:224028", "title": "Transport of proteins across the mitochondrial outer membrane. A precursor form of the cytoplasmically made intermembrane enzyme cytochrome c peroxidase.", "content": "Cytochrome c peroxidase, a cytoplasmically made enzyme located between the inner and outer membrane of yeast mitochondria, is synthesized as larger precursor in a reticulocyte cell-free lysate as well as in pulsed yeast spheroplasts. When the pulsed spheroplasts are chased, the precursor is converted to the mature apoprotein. When the in vitro synthesized precursor is incubated with isolated yeast mitochondria in the absence of protein synthesis, it is cleaved to the mature form; the mature form co-sediments with the mitochondria and is resistant to externally added proteases. These results, in conjunction with those reported earlier (Maccecchini, M.-L., Rudin, Y., Blobel, G., and Schatz, G. (1979) Proc. Natl. Acad. Sci. U.S.A. 76, 343-347) suggest that the mechanism of protein transport into the mitochondrial intermembrane space is quite similar to that of protein transport into the matrix or the inner membrane.", "contents": "Transport of proteins across the mitochondrial outer membrane. A precursor form of the cytoplasmically made intermembrane enzyme cytochrome c peroxidase. Cytochrome c peroxidase, a cytoplasmically made enzyme located between the inner and outer membrane of yeast mitochondria, is synthesized as larger precursor in a reticulocyte cell-free lysate as well as in pulsed yeast spheroplasts. When the pulsed spheroplasts are chased, the precursor is converted to the mature apoprotein. When the in vitro synthesized precursor is incubated with isolated yeast mitochondria in the absence of protein synthesis, it is cleaved to the mature form; the mature form co-sediments with the mitochondria and is resistant to externally added proteases. These results, in conjunction with those reported earlier (Maccecchini, M.-L., Rudin, Y., Blobel, G., and Schatz, G. (1979) Proc. Natl. Acad. Sci. U.S.A. 76, 343-347) suggest that the mechanism of protein transport into the mitochondrial intermembrane space is quite similar to that of protein transport into the matrix or the inner membrane."}
{"id": "PMID:224029", "title": "Stereochemistry of hydrolysis by snake venom phosphodiesterase.", "content": "[18O]Adenosine 5'-O-phosphorothioate-O-p-nitrophenyl ester was prepared by saponification of the bis (-O,O-p-nitrophenyl ester) with K18OH. Only the diastereoisomer with the Rp configuration si a substrate for snake venom phosphodiesterase. The asymmetrically labeled [18O]adenosine 5'-O-phosphorothioate formed in this reaction was converted enzymatically to [18O]adenosine 5'-(1-thiodiphosphate) with the Sp configuration. The position of the 18O label, either bridging [1,2-mu-18O] or nonbridging [1-18O] was then determined. The results show that the reaction catalyzed by snake venom phosphodiesterase takes place with retention of configuration at phosphorus. This indicates that the hydrolysis proceeds via a covalent nucleotide enzyme intermediate.", "contents": "Stereochemistry of hydrolysis by snake venom phosphodiesterase. [18O]Adenosine 5'-O-phosphorothioate-O-p-nitrophenyl ester was prepared by saponification of the bis (-O,O-p-nitrophenyl ester) with K18OH. Only the diastereoisomer with the Rp configuration si a substrate for snake venom phosphodiesterase. The asymmetrically labeled [18O]adenosine 5'-O-phosphorothioate formed in this reaction was converted enzymatically to [18O]adenosine 5'-(1-thiodiphosphate) with the Sp configuration. The position of the 18O label, either bridging [1,2-mu-18O] or nonbridging [1-18O] was then determined. The results show that the reaction catalyzed by snake venom phosphodiesterase takes place with retention of configuration at phosphorus. This indicates that the hydrolysis proceeds via a covalent nucleotide enzyme intermediate."}
{"id": "PMID:224030", "title": "Hyperfine structure resolved by 2 to 4 GHz EPR of cytochrome c oxidase.", "content": "Using low frequency 2 to 4 GHz EPR at 10 K, we have resolved previously unseen hyperfine structure associated with the EPR-detectable copper signal of cytochrome c oxidase. The observed hyperfine structure appears consistent with hyperfine coupling to copper; although to account for all of the observed structure, an additional magnetic interaction is required as well. This work points out the utility of the 2 to 4 GHz EPR technique for resolving electronic hyperfine structural information from copper and possibly other paramagnetic sites in biomolecules when random variation in electronic g values is a cause of EPR line-broadening.", "contents": "Hyperfine structure resolved by 2 to 4 GHz EPR of cytochrome c oxidase. Using low frequency 2 to 4 GHz EPR at 10 K, we have resolved previously unseen hyperfine structure associated with the EPR-detectable copper signal of cytochrome c oxidase. The observed hyperfine structure appears consistent with hyperfine coupling to copper; although to account for all of the observed structure, an additional magnetic interaction is required as well. This work points out the utility of the 2 to 4 GHz EPR technique for resolving electronic hyperfine structural information from copper and possibly other paramagnetic sites in biomolecules when random variation in electronic g values is a cause of EPR line-broadening."}
{"id": "PMID:224031", "title": "Affinity labeling of catalytic subunit of bovine heart muscle cyclic AMP-dependent protein kinase by 5'-p-fluorosulfonylbenzoyladenosine.", "content": "Incubation of 5'-p-fluorosulfonylbenzoyladenosine with the catalytic subunit of bovine cardiac muscle cyclic AMP-dependent protein kinase led to the formation of an inactive enzyme irreversibly modified with approximately one mol of reagent per mol of subunit. The inactivation reaction followed pseudofirst order kinetics. The rate of inactivation at various reagent concentrations exhibited saturation kinetics implying that the reagent reversibly binds to the enzyme prior to inactivation. The addition of MgATP, MgADP, or MgAMP-PNP to the reaction mixture fully protected the enzyme from inactivation by 5'-p-fluorosulfonylbenzoyladenosine. The reagent was demonstrated to be a competitive inhibitor of MgATP with a Ki of 0.235 mM. Metal-free nucleotides were without effect upon the reaction rate while metal ions alone accelerated the inactivation rate up to 7-fold. The inclusion of casein or synthetic peptide substrate in the incubation mixture did not affect the reaction kinetics. Reaction of 5'-p-fluorosulfonylbenzoyladenosine with the kinase subunit exhibits all of the characteristics of affinity labeling of the MgATP-binding site.", "contents": "Affinity labeling of catalytic subunit of bovine heart muscle cyclic AMP-dependent protein kinase by 5'-p-fluorosulfonylbenzoyladenosine. Incubation of 5'-p-fluorosulfonylbenzoyladenosine with the catalytic subunit of bovine cardiac muscle cyclic AMP-dependent protein kinase led to the formation of an inactive enzyme irreversibly modified with approximately one mol of reagent per mol of subunit. The inactivation reaction followed pseudofirst order kinetics. The rate of inactivation at various reagent concentrations exhibited saturation kinetics implying that the reagent reversibly binds to the enzyme prior to inactivation. The addition of MgATP, MgADP, or MgAMP-PNP to the reaction mixture fully protected the enzyme from inactivation by 5'-p-fluorosulfonylbenzoyladenosine. The reagent was demonstrated to be a competitive inhibitor of MgATP with a Ki of 0.235 mM. Metal-free nucleotides were without effect upon the reaction rate while metal ions alone accelerated the inactivation rate up to 7-fold. The inclusion of casein or synthetic peptide substrate in the incubation mixture did not affect the reaction kinetics. Reaction of 5'-p-fluorosulfonylbenzoyladenosine with the kinase subunit exhibits all of the characteristics of affinity labeling of the MgATP-binding site."}
{"id": "PMID:224032", "title": "Calcium dependence of hormone-stimulated cAMP accumulation in intact glial tumor cells.", "content": "The Ca2+ content of glial tumor (C6) cells was reduced approximately 5-fold by repeated treatment with media containing ethylene glycol bis(beta-aminoethyl ether) N,N'-tetraacetic acid (EGTA) without loss of cellular viability. The ability of the cells to accumulate cAMP in response to beta-adrenergic agonists was reduced 60 to 70% following Ca2+ depletion. Ca2+ did not affect the apparent KACT for norepinephrine, nor did it change the concentration of propranolol required to produce 50% inhibition of the maximal norepinephrine response. Phentolamine did not alter the Ca2+ dependence of the response. The binding of dihydroalprenolol by intact C6 cells was not influenced by Ca2+. Furthermore, pretreatment with norepinephrine did not affect the Ca2+ dependence of cAMP accumulation. The effects of Ca2+, therefore, appeared to be exerted on components of the adenylate cyclase system other than the catecholamine receptor. Micromolar free Ca2+ concentration in the extracellular medium were sufficient to restore a maximal norepinephrine response to Ca2+-depeleted cells. The effect of Ca2+ on cAMP accumulation in response to hormone was immediate and was rapidly reversible upon the addition of EGTA in excess of the cation. Cells in media containing Ca2+ exhibited a characteristic biphasic time course of cAMP accumulation; with Ca2+-depleted cells cAMP was accumulated more slowly and the subsequent decline in cAMP content was also reduced. Verapamil, an inhibitor of plasmalemmal Ca2+ influx, decreased the Ca2+-dependent component of the cAMP accumulation when added prior to the cation. The effect of Ca2+ on cAMP accumulation was reduced more extensively by pretreatment of cells at 45 degrees C under Ca2+-depleted (80% loss) than under Ca2+-restored (30% loss) conditions. Trifluoperazine at micromolar concentrations decreased the Ca2+-dependent increment in accumulation of cAMP in Ca2+-restored cells. This inhibition was not overcome by increasing concentrations of norepinephrine or of extracellular Ca2+.", "contents": "Calcium dependence of hormone-stimulated cAMP accumulation in intact glial tumor cells. The Ca2+ content of glial tumor (C6) cells was reduced approximately 5-fold by repeated treatment with media containing ethylene glycol bis(beta-aminoethyl ether) N,N'-tetraacetic acid (EGTA) without loss of cellular viability. The ability of the cells to accumulate cAMP in response to beta-adrenergic agonists was reduced 60 to 70% following Ca2+ depletion. Ca2+ did not affect the apparent KACT for norepinephrine, nor did it change the concentration of propranolol required to produce 50% inhibition of the maximal norepinephrine response. Phentolamine did not alter the Ca2+ dependence of the response. The binding of dihydroalprenolol by intact C6 cells was not influenced by Ca2+. Furthermore, pretreatment with norepinephrine did not affect the Ca2+ dependence of cAMP accumulation. The effects of Ca2+, therefore, appeared to be exerted on components of the adenylate cyclase system other than the catecholamine receptor. Micromolar free Ca2+ concentration in the extracellular medium were sufficient to restore a maximal norepinephrine response to Ca2+-depeleted cells. The effect of Ca2+ on cAMP accumulation in response to hormone was immediate and was rapidly reversible upon the addition of EGTA in excess of the cation. Cells in media containing Ca2+ exhibited a characteristic biphasic time course of cAMP accumulation; with Ca2+-depleted cells cAMP was accumulated more slowly and the subsequent decline in cAMP content was also reduced. Verapamil, an inhibitor of plasmalemmal Ca2+ influx, decreased the Ca2+-dependent component of the cAMP accumulation when added prior to the cation. The effect of Ca2+ on cAMP accumulation was reduced more extensively by pretreatment of cells at 45 degrees C under Ca2+-depleted (80% loss) than under Ca2+-restored (30% loss) conditions. Trifluoperazine at micromolar concentrations decreased the Ca2+-dependent increment in accumulation of cAMP in Ca2+-restored cells. This inhibition was not overcome by increasing concentrations of norepinephrine or of extracellular Ca2+."}
{"id": "PMID:224034", "title": "Observations on the mechanism of the reversible epimerization of GDP-D-mannose to GDP-L-galactose by an enzyme from Chlorella pyrenoidosa.", "content": "An enzyme fraction from the green alga Chlorella pyrenoidosa that catalyzes the reversible epimerization of guanosine 5'-diphosphate D-mannose to guanosine 5'-diphosphate L-galactose brings about the incorporation of tritium from  tritium-labeled water into the hexosyl moieties of those sugar nucleotides. The hexoses were degraded by periodate oxidation whereby the tritium was found to be equally distributed between carbon atoms 3 and 5. That observation was taken to imply that the epimerizations proceed via ene-diol intermediates.", "contents": "Observations on the mechanism of the reversible epimerization of GDP-D-mannose to GDP-L-galactose by an enzyme from Chlorella pyrenoidosa. An enzyme fraction from the green alga Chlorella pyrenoidosa that catalyzes the reversible epimerization of guanosine 5'-diphosphate D-mannose to guanosine 5'-diphosphate L-galactose brings about the incorporation of tritium from  tritium-labeled water into the hexosyl moieties of those sugar nucleotides. The hexoses were degraded by periodate oxidation whereby the tritium was found to be equally distributed between carbon atoms 3 and 5. That observation was taken to imply that the epimerizations proceed via ene-diol intermediates."}
{"id": "PMID:224035", "title": "Biosynthesis of the Ca2+- and Mg2+-dependent adenosine triphosphatase of sarcoplasmic reticulum in cell cultures of embryonic chick heart.", "content": "The biosynthesis of the Ca2+- and Mg2+-dependent adenosine triphosphatase of sarcoplasmic reticulum was studied in cell cultures of embryonic chick heart. Rates of synthesis were estimated from the incorporation of tritium-labeled leucine into the ATPase. Newly synthesized ATPase was isolated from cells by immunoprecipitation. Radioactive leucine incorporation into the ATPase was determined by gel electrophoresis of the immunoprecipitates and counting of gel slices containing the ATPase band. Accumulation of the ATPase was estimated from the concentration of Ca2+ and Mg2+-dependent, hydroxylamine-sensitive phosphoprotein in the whole cell membrane fraction of cultured cells. Embryonic heart cells cultured in a medium which permitted cell proliferation showed approximately linearly increasing rates of ATPase synthesis and accumulation/culture plate as the cells proliferated. When cells were cultured in a serum-free medium, cell proliferation was inhibited and there was no sustained increase in the rate of ATPase synthesis or accumulation. Inclusion of isoproterenol or dibutyryl cyclic AMP at concentrations of 10 microM up to 1 mM in serum-free culture medium failed to stimulate significantly ATPase synthesis.", "contents": "Biosynthesis of the Ca2+- and Mg2+-dependent adenosine triphosphatase of sarcoplasmic reticulum in cell cultures of embryonic chick heart. The biosynthesis of the Ca2+- and Mg2+-dependent adenosine triphosphatase of sarcoplasmic reticulum was studied in cell cultures of embryonic chick heart. Rates of synthesis were estimated from the incorporation of tritium-labeled leucine into the ATPase. Newly synthesized ATPase was isolated from cells by immunoprecipitation. Radioactive leucine incorporation into the ATPase was determined by gel electrophoresis of the immunoprecipitates and counting of gel slices containing the ATPase band. Accumulation of the ATPase was estimated from the concentration of Ca2+ and Mg2+-dependent, hydroxylamine-sensitive phosphoprotein in the whole cell membrane fraction of cultured cells. Embryonic heart cells cultured in a medium which permitted cell proliferation showed approximately linearly increasing rates of ATPase synthesis and accumulation/culture plate as the cells proliferated. When cells were cultured in a serum-free medium, cell proliferation was inhibited and there was no sustained increase in the rate of ATPase synthesis or accumulation. Inclusion of isoproterenol or dibutyryl cyclic AMP at concentrations of 10 microM up to 1 mM in serum-free culture medium failed to stimulate significantly ATPase synthesis."}
{"id": "PMID:224036", "title": "Cytochrome c oxidase from bakers' yeast. Photolabeling of subunits exposed to the lipid bilayer.", "content": "Yeast mitochondria and purified yeast cytochrome c oxidase incorporated into micelles of the nonionic detergent Tween 80 were equilibrated with the hydrophobic aryl azides 5-[125I]iodonaphthyl-1-azide or S-(4-azido-2-nitrophenyl)-[35S]thiophenol. The azides were then converted to highly reactive nitrenes by flash photolysis or by illumination for 2 min and the derivatized cytochrome c oxidase subunits were identified by gel electrophoresis and radioactivity measurements. 5-[125I]Iodonaphthyl-1-azide labeled mainly the three mitochondrially made Subunits I to III and the cytoplasmically made Subunit VII. Subunits IV to VI or cytochrome c bound to the purified enzyme were labeled 9- to 90-fold less. Essentially the same result was obtained with S-(4-azido-2-nitrophenyl)-[35S]thiophenol except that Subunit V was labeled as well. In contrast, all seven subunits as well as cytochrome c were heavily labeled when the enzyme was dissociated with dodecyl sulfate prior to photolabeling with either of the two probes. These data indicate that all subunits of yeast cytochrome c oxidase except Subunits IV and VI are at least partly embedded in the lipid bilayer of the mitochondrial inner membrane.", "contents": "Cytochrome c oxidase from bakers' yeast. Photolabeling of subunits exposed to the lipid bilayer. Yeast mitochondria and purified yeast cytochrome c oxidase incorporated into micelles of the nonionic detergent Tween 80 were equilibrated with the hydrophobic aryl azides 5-[125I]iodonaphthyl-1-azide or S-(4-azido-2-nitrophenyl)-[35S]thiophenol. The azides were then converted to highly reactive nitrenes by flash photolysis or by illumination for 2 min and the derivatized cytochrome c oxidase subunits were identified by gel electrophoresis and radioactivity measurements. 5-[125I]Iodonaphthyl-1-azide labeled mainly the three mitochondrially made Subunits I to III and the cytoplasmically made Subunit VII. Subunits IV to VI or cytochrome c bound to the purified enzyme were labeled 9- to 90-fold less. Essentially the same result was obtained with S-(4-azido-2-nitrophenyl)-[35S]thiophenol except that Subunit V was labeled as well. In contrast, all seven subunits as well as cytochrome c were heavily labeled when the enzyme was dissociated with dodecyl sulfate prior to photolabeling with either of the two probes. These data indicate that all subunits of yeast cytochrome c oxidase except Subunits IV and VI are at least partly embedded in the lipid bilayer of the mitochondrial inner membrane."}
{"id": "PMID:224037", "title": "Membrane-dependent guanine nucleotide binding and GTPase activities of soluble protein from bovine rod cell outer segments.", "content": "Soluble proteins can be extracted by osmotic shock of purified rod (photoreceptor cell) outer segments that have intact plasma membranes. The soluble proteins include a component that contains tightly bound GDP-Exchange of this GDP with exogenous nucleotide is catalyzed by (and requires) the membranes from the outer segments. ATP does not participate in these reactions. Approximately one-half of the binding sites in the soluble component require GTP as the source of exogenous nucleotide; the remainder accept GTP or GDP with equal facility. When exogenous GTP is the source of bound nucleotide, it is found in the complex in the form of GDP. Exchange of bound nucleotide with GTP is stoichiometrically related to GTPase activity; this activity is highly dependent upon the presence of both membranes and soluble protein. The soluble nucleotide binding protein was purified by making use of the fact that it binds tightly to the membranes (under conditions of moderate ionic strength) in the absence of GTP and can be eluted by solutions containing low concentrations of GTP (but not GDP or ATP, nor can it be eluted by GTP-free solutions of low ionic strength). The purified protein contains two polypeptide chains of molecular weights 41,000 and 37,000; these are the major species that can be extracted from the outer segments by osmotic shock, and they constitute approximately 7% of the total protein of the isolated organelle.", "contents": "Membrane-dependent guanine nucleotide binding and GTPase activities of soluble protein from bovine rod cell outer segments. Soluble proteins can be extracted by osmotic shock of purified rod (photoreceptor cell) outer segments that have intact plasma membranes. The soluble proteins include a component that contains tightly bound GDP-Exchange of this GDP with exogenous nucleotide is catalyzed by (and requires) the membranes from the outer segments. ATP does not participate in these reactions. Approximately one-half of the binding sites in the soluble component require GTP as the source of exogenous nucleotide; the remainder accept GTP or GDP with equal facility. When exogenous GTP is the source of bound nucleotide, it is found in the complex in the form of GDP. Exchange of bound nucleotide with GTP is stoichiometrically related to GTPase activity; this activity is highly dependent upon the presence of both membranes and soluble protein. The soluble nucleotide binding protein was purified by making use of the fact that it binds tightly to the membranes (under conditions of moderate ionic strength) in the absence of GTP and can be eluted by solutions containing low concentrations of GTP (but not GDP or ATP, nor can it be eluted by GTP-free solutions of low ionic strength). The purified protein contains two polypeptide chains of molecular weights 41,000 and 37,000; these are the major species that can be extracted from the outer segments by osmotic shock, and they constitute approximately 7% of the total protein of the isolated organelle."}
{"id": "PMID:224038", "title": "Synthesis and secretion of corticotropins, melanotropins, and endorphins by rat intermediate pituitary cells.", "content": "The synthesis and secretion of various intermediate pituitary proteins was studied by using dispersed intermediate pituitary cell suspensions. Control studies indicated that the isolated cells were obtained in good yield and that after more than 24 h in culture the isolated cells continued to synthesize a collection of proteins similar to those found in freshly extracted intermediate pituitary tissue. Rat intermediate pituitary cells synthesized a molecule (Mr = 30,000; called 30K) that contained antigenic determinants for beta-endorphin, gamma-lipotropin, corticotropin (ACTH), and 16K fragment (the NH2-terminal region of mouse tumor cell pro-ACTH/endorphin). This 30K molecule, two high molecular weight forms of ACTH(13K and 20K), and 16K fragment were all shown to be glycoproteins. Continuous labeling and pulse-chase incubations were used to define the intracellular biosynthetic processing of the 30K molecule. After a 15-min pulse incubation the 30K molecule was the only labeled protein containing antigenic determinants for beta-endorphin, gamma-lipotropin, ACTH, or 16K fragment. A beta-lipotropin-like molecule served as a biosynthetic intermediate in the production of proteins similar to beta-endorphin and gamma-lipotropin. Methionine-enkephalin and alpha-endorphin were not major products in the intermediate lobe cells. Molecules similar to alpha-melanocyte-stimulating hormone and corticotropin-like intermediate lobe peptide (ACTH(18-39)) were also derived from the same 30K molecule; 20K ACTH served as a biosynthetic intermediate in this conversion. In rat intermediate pituitary cells ACTH(1-39) was not a major final product of the intracellular biosynthetic processing of the 30K molecule. The 30K molecule also served as a precursor to a protein similar to mouse tumor cell 16K fragment and related smaller proteins. With rat intermediate pituitary cells, pulse-chase experiments utilizing [35S]methionine demonstrated almost quantitative conversion of the 30K precursor into labeled proteins similar to beta-endorphin and alpha-melanocyte-stimulating hormone. In the absence of added secretagogues, small amounts of all of the smaller proteins derived from the 30K precursor were secreted coordinately into the culture medium.", "contents": "Synthesis and secretion of corticotropins, melanotropins, and endorphins by rat intermediate pituitary cells. The synthesis and secretion of various intermediate pituitary proteins was studied by using dispersed intermediate pituitary cell suspensions. Control studies indicated that the isolated cells were obtained in good yield and that after more than 24 h in culture the isolated cells continued to synthesize a collection of proteins similar to those found in freshly extracted intermediate pituitary tissue. Rat intermediate pituitary cells synthesized a molecule (Mr = 30,000; called 30K) that contained antigenic determinants for beta-endorphin, gamma-lipotropin, corticotropin (ACTH), and 16K fragment (the NH2-terminal region of mouse tumor cell pro-ACTH/endorphin). This 30K molecule, two high molecular weight forms of ACTH(13K and 20K), and 16K fragment were all shown to be glycoproteins. Continuous labeling and pulse-chase incubations were used to define the intracellular biosynthetic processing of the 30K molecule. After a 15-min pulse incubation the 30K molecule was the only labeled protein containing antigenic determinants for beta-endorphin, gamma-lipotropin, ACTH, or 16K fragment. A beta-lipotropin-like molecule served as a biosynthetic intermediate in the production of proteins similar to beta-endorphin and gamma-lipotropin. Methionine-enkephalin and alpha-endorphin were not major products in the intermediate lobe cells. Molecules similar to alpha-melanocyte-stimulating hormone and corticotropin-like intermediate lobe peptide (ACTH(18-39)) were also derived from the same 30K molecule; 20K ACTH served as a biosynthetic intermediate in this conversion. In rat intermediate pituitary cells ACTH(1-39) was not a major final product of the intracellular biosynthetic processing of the 30K molecule. The 30K molecule also served as a precursor to a protein similar to mouse tumor cell 16K fragment and related smaller proteins. With rat intermediate pituitary cells, pulse-chase experiments utilizing [35S]methionine demonstrated almost quantitative conversion of the 30K precursor into labeled proteins similar to beta-endorphin and alpha-melanocyte-stimulating hormone. In the absence of added secretagogues, small amounts of all of the smaller proteins derived from the 30K precursor were secreted coordinately into the culture medium."}
{"id": "PMID:224040", "title": "Modulation of protein synthesis by nerve growth factor.", "content": "The effects of nerve growth factor (NGF) and two analogs of cAMP have been studied in the PC12 line of rat pheochromocytoma cells. We have used two-dimensional gel electrophoresis to detect more than 800 proteins from control and NGF-treated cells. Of these proteins, none were qualitatively repressed in response to NGF, and no new proteins appeared after NGF treatment. Visual inspection of the gels showed that approximately 5% of the proteins were detectably increased or decreased in rate of synthesis by NGF, and each of these changes was mimicked by both cAMP analogs. The two-dimensional gel data were further analyzed by a computerized scanning system. This analysis has revealed many significant changes that are smaller than those detected by eye. Approximately 25 to 30% of the proteins analyzed were found to be altered in rate of synthesis by 30% or more. Statistical analysis has shown that the response to NGF and the response to dibutyryl cAMP are highly correlated, even down to changes as small as 30%. No proteins were found to be significantly altered by both dibutyryl cAMP and 8-bromo cAMP, but not by NGF. These results show that NGF causes only quantitative modulations of protein synthesis in PC12 cells, and these data strongly suggest that the response of PC12 cells to NGF is mediated by cAMP.", "contents": "Modulation of protein synthesis by nerve growth factor. The effects of nerve growth factor (NGF) and two analogs of cAMP have been studied in the PC12 line of rat pheochromocytoma cells. We have used two-dimensional gel electrophoresis to detect more than 800 proteins from control and NGF-treated cells. Of these proteins, none were qualitatively repressed in response to NGF, and no new proteins appeared after NGF treatment. Visual inspection of the gels showed that approximately 5% of the proteins were detectably increased or decreased in rate of synthesis by NGF, and each of these changes was mimicked by both cAMP analogs. The two-dimensional gel data were further analyzed by a computerized scanning system. This analysis has revealed many significant changes that are smaller than those detected by eye. Approximately 25 to 30% of the proteins analyzed were found to be altered in rate of synthesis by 30% or more. Statistical analysis has shown that the response to NGF and the response to dibutyryl cAMP are highly correlated, even down to changes as small as 30%. No proteins were found to be significantly altered by both dibutyryl cAMP and 8-bromo cAMP, but not by NGF. These results show that NGF causes only quantitative modulations of protein synthesis in PC12 cells, and these data strongly suggest that the response of PC12 cells to NGF is mediated by cAMP."}
{"id": "PMID:224041", "title": "Crystallographic symmetry and coenzyme binding properties of D-glyceraldehyde-3-phosphate dehydrogenase from the tail muscle of Palinurus vulgaris.", "content": "Crystals of apo- and holo-D-glyceraldehyde-3-phosphate dehydrogenase from the tail muscle of the Mediterranean lobster Palinurus vulgaris, previously found to be suitable for single crystal microspectrophotometric studies of catalytic activity in the crystalline state, have been examined by x-ray crystallography. The two forms are isomorphous, space group C 2 with cell dimensions a=128.4 A, b=99.9 A, c=80.3 A,beta=113.4 degrees. These data are consistent with a molecular weight of 73,000 in the crystallographic asymmetric unit, indicating that the tetrameric molecule possesses an exact 2-fold axis both in the presence and in the absence of NAD+. Analysis of the intensity distribution of conventional x-ray precession photographs shows that two further noncrystallographic diads are present and that the molecule has the 2 pseudo 22 symmetry found in other D-glyceraldehyde-3-phosphate dehydrogenases. Binding of NAD+ to apoenzyme in solution, at 25 degrees C, is anticooperative and it can be satisfactorily described by assuming two classes of coenzyme binding sites.", "contents": "Crystallographic symmetry and coenzyme binding properties of D-glyceraldehyde-3-phosphate dehydrogenase from the tail muscle of Palinurus vulgaris. Crystals of apo- and holo-D-glyceraldehyde-3-phosphate dehydrogenase from the tail muscle of the Mediterranean lobster Palinurus vulgaris, previously found to be suitable for single crystal microspectrophotometric studies of catalytic activity in the crystalline state, have been examined by x-ray crystallography. The two forms are isomorphous, space group C 2 with cell dimensions a=128.4 A, b=99.9 A, c=80.3 A,beta=113.4 degrees. These data are consistent with a molecular weight of 73,000 in the crystallographic asymmetric unit, indicating that the tetrameric molecule possesses an exact 2-fold axis both in the presence and in the absence of NAD+. Analysis of the intensity distribution of conventional x-ray precession photographs shows that two further noncrystallographic diads are present and that the molecule has the 2 pseudo 22 symmetry found in other D-glyceraldehyde-3-phosphate dehydrogenases. Binding of NAD+ to apoenzyme in solution, at 25 degrees C, is anticooperative and it can be satisfactorily described by assuming two classes of coenzyme binding sites."}
{"id": "PMID:224043", "title": "The purification and properties of a double-stranded DNA-binding protein encoded by the gene D5 of bacteriophage T5.", "content": "We have purified a DNA-binding protein from bacteriophage T5-infected cells. The protein is the product of the T5 gene D5 and is produced in quantities ultimately exceeding 2% of the total cell protein. The protein has no tendency to aggregate and exists in solution as a monomer of about 29,000 daltons. Although the protein binds with a high affinity to both single-stranded (fd, T7) and duplex DNA (T5, T7), there is a preferred binding to duplex DNA. The binding of the gene D5 protein to duplex DNA is cooperative with an estimated dissociation constant of 6.27 x 10(-10) M and leads to the production of a more condensed form of the DNA. In contrast, binding of the gene D5 protein to single-stranded DNA is noncooperative with an estimated dissociation constant of only 1.85 x 10(-8) M and produces a sedimentation shift in the DNA proportional to the added mass of the protein. The protein product of the gene D5 of bacteriophage T5 is known to be required for both T5 DNA replication and for the inhibition of early phage gene expression. We also show here that the protein is required to initiate transcription of the late region of the T5 genome.", "contents": "The purification and properties of a double-stranded DNA-binding protein encoded by the gene D5 of bacteriophage T5. We have purified a DNA-binding protein from bacteriophage T5-infected cells. The protein is the product of the T5 gene D5 and is produced in quantities ultimately exceeding 2% of the total cell protein. The protein has no tendency to aggregate and exists in solution as a monomer of about 29,000 daltons. Although the protein binds with a high affinity to both single-stranded (fd, T7) and duplex DNA (T5, T7), there is a preferred binding to duplex DNA. The binding of the gene D5 protein to duplex DNA is cooperative with an estimated dissociation constant of 6.27 x 10(-10) M and leads to the production of a more condensed form of the DNA. In contrast, binding of the gene D5 protein to single-stranded DNA is noncooperative with an estimated dissociation constant of only 1.85 x 10(-8) M and produces a sedimentation shift in the DNA proportional to the added mass of the protein. The protein product of the gene D5 of bacteriophage T5 is known to be required for both T5 DNA replication and for the inhibition of early phage gene expression. We also show here that the protein is required to initiate transcription of the late region of the T5 genome."}
{"id": "PMID:224045", "title": "Kinetic studies on the effect of the heme iron(III) on the protein folding of ferricytochrome c.", "content": "The three-dimensional conformation of ferricytochrome c results from specific folding of the polypeptide chain around the covalently bound heme so that His-18 and Met-80 are axially coordinated to the Fe(III). The Fe(III)-free, porphyrin protein has an intrinsic viscosity, sedimentation coefficient, and circular dichroism indicative of a compact, globular protein conformation comparable to the holoprotein. Both the porphyrin protein and ferricytochrome c are reversibly denatured by guanidinium chloride. Refolding of the porphyrin protein occurs in essentially a single, exceptionally rapid kinetic phase (tau = 14 ms, 0.75 M guanidinium chloride, pH 6.5, 25 degrees C); whereas refolding of ferricytochrome c occurs in two slower kinetic phases (TAU 1 = 0.10 S, TAU 2 = 20 S) UNDER COMPARABLE CONDITIONS. The presence of Fe(III) in the metalloporphyrin of ferricytochrome c thus has a major effect on the protein folding kinetics. The slow kinetic phase is evidently due to this effect of Fe(III) and not to the slow cis-trans isomerism of the peptide bond of proline residues as has been suggested.", "contents": "Kinetic studies on the effect of the heme iron(III) on the protein folding of ferricytochrome c. The three-dimensional conformation of ferricytochrome c results from specific folding of the polypeptide chain around the covalently bound heme so that His-18 and Met-80 are axially coordinated to the Fe(III). The Fe(III)-free, porphyrin protein has an intrinsic viscosity, sedimentation coefficient, and circular dichroism indicative of a compact, globular protein conformation comparable to the holoprotein. Both the porphyrin protein and ferricytochrome c are reversibly denatured by guanidinium chloride. Refolding of the porphyrin protein occurs in essentially a single, exceptionally rapid kinetic phase (tau = 14 ms, 0.75 M guanidinium chloride, pH 6.5, 25 degrees C); whereas refolding of ferricytochrome c occurs in two slower kinetic phases (TAU 1 = 0.10 S, TAU 2 = 20 S) UNDER COMPARABLE CONDITIONS. The presence of Fe(III) in the metalloporphyrin of ferricytochrome c thus has a major effect on the protein folding kinetics. The slow kinetic phase is evidently due to this effect of Fe(III) and not to the slow cis-trans isomerism of the peptide bond of proline residues as has been suggested."}
{"id": "PMID:224046", "title": "A poly(dT)-stimulated ATPase activity associated with simian virus 40 large T antigen.", "content": "Highly purified SV40 large T antigen exhibits an ATPase activity which can be stimulated approximately 7-fold by the DNA homopolymer poly(dT). The poly(dT)-stimulated enzyme can hydrolyze various ribonucleotide and deoxyribonucleotide triphosphates, with ATP and dATP serving as the best substrates. Purified large T antigen hydrolyzes ATP to ADP and Pi, with a maximum specific activity of 13.5 mumol of inorganic phosphate released per h per mg of protein. Of the various natural and synthetic polynucleotides tested, poly(dT) was by far the best activator. Long chain poly(dT) molecules are much more effective activators than are short chain length oligo(dT) molecules. The highly purified large T antigen contains no detectable protein kinase activity.", "contents": "A poly(dT)-stimulated ATPase activity associated with simian virus 40 large T antigen. Highly purified SV40 large T antigen exhibits an ATPase activity which can be stimulated approximately 7-fold by the DNA homopolymer poly(dT). The poly(dT)-stimulated enzyme can hydrolyze various ribonucleotide and deoxyribonucleotide triphosphates, with ATP and dATP serving as the best substrates. Purified large T antigen hydrolyzes ATP to ADP and Pi, with a maximum specific activity of 13.5 mumol of inorganic phosphate released per h per mg of protein. Of the various natural and synthetic polynucleotides tested, poly(dT) was by far the best activator. Long chain poly(dT) molecules are much more effective activators than are short chain length oligo(dT) molecules. The highly purified large T antigen contains no detectable protein kinase activity."}
{"id": "PMID:224048", "title": "Biophysical properties of a major membrane phospholipid, dielaidoylphosphatidylethanolamine, found in an Escherichia coli fatty acid auxotroph.", "content": "Dielaidoylphosphatidylethanolamine, a principal lipid component of membranes of Escherichia coli fatty acid auxotrophs enriched in elaidic acid, has been studied by paramagnetic resonance, fluorescence, and calorimetric methods. EPR measurements with perdeutero-di-tert-butylnitroxide and 2,2,6,6-tetramethyl piperidine-1-oxyl indicate that, when dispersed in aqueous media, this phospholipid undergoes an abrupt order leads to disorder transition at 37.5 degrees C and 36.5 C, respectively. A similar transition temperature is suggested by experiments with 9-doxyl-dimyristoylphosphatidylethanolamine (DEPE). cis- and trans-Parinaric-acid fluorescence polarization measurements indicate that the midpoint of this transition occurs at 34.0 degrees C and 35.5 degrees C, respectively. Differential scanning calorimetry of DEPE revealed a single, sharp endotherm at 38.5 degrees C with increasing temperature; two exotherms of similar magnitude were observed at 36.5 degrees C and 34.5 degrees C upon cooling. This double transition was not observed by any of the other methods. From these results we conclude that the major structural transition at 30-31 degrees C observed previously with 5-, 12-, and 16-doxyl stearate in intact E. coli membranes is due to the DEPE present (Morrisett, J.D., Pownall, H.J., Plumlee, R.T., Smith, L.C., Zehner, Z.E., Esfahani, M., and Wakil, S.J. (1975) J. Biol. Chem. 250, 6969-6976).", "contents": "Biophysical properties of a major membrane phospholipid, dielaidoylphosphatidylethanolamine, found in an Escherichia coli fatty acid auxotroph. Dielaidoylphosphatidylethanolamine, a principal lipid component of membranes of Escherichia coli fatty acid auxotrophs enriched in elaidic acid, has been studied by paramagnetic resonance, fluorescence, and calorimetric methods. EPR measurements with perdeutero-di-tert-butylnitroxide and 2,2,6,6-tetramethyl piperidine-1-oxyl indicate that, when dispersed in aqueous media, this phospholipid undergoes an abrupt order leads to disorder transition at 37.5 degrees C and 36.5 C, respectively. A similar transition temperature is suggested by experiments with 9-doxyl-dimyristoylphosphatidylethanolamine (DEPE). cis- and trans-Parinaric-acid fluorescence polarization measurements indicate that the midpoint of this transition occurs at 34.0 degrees C and 35.5 degrees C, respectively. Differential scanning calorimetry of DEPE revealed a single, sharp endotherm at 38.5 degrees C with increasing temperature; two exotherms of similar magnitude were observed at 36.5 degrees C and 34.5 degrees C upon cooling. This double transition was not observed by any of the other methods. From these results we conclude that the major structural transition at 30-31 degrees C observed previously with 5-, 12-, and 16-doxyl stearate in intact E. coli membranes is due to the DEPE present (Morrisett, J.D., Pownall, H.J., Plumlee, R.T., Smith, L.C., Zehner, Z.E., Esfahani, M., and Wakil, S.J. (1975) J. Biol. Chem. 250, 6969-6976)."}
{"id": "PMID:224050", "title": "Contribution of cyclic adenosine 3':5'-monophosphate to the regulation of bacterial glycogen synthesis in vivo. Effect of carbon source and cyclic adenosine 3':5'-monophosphate on the quantitative relationship between the rate of glycogen synthesis and the cellular concentrations of glucose 6-phosphate and fructose 1,6-diphosphate in Escherichia coli.", "content": "When either fructose, glycerol, or succinate served as a sole source of carbon and energy in nitrogen-starved cultures of Escherichia coli W4597(K) the values of the kinetic constants of the equation that expresses the relationship between glycogen synthesis and hexose phosphates were different from the values observed when glucose was the sole source of carbon and energy. Addition of glucose during either exponential growth or nitrogen starvation to a culture using one of the other carbon sources slowed the rate of glycogen synthesis and shifted the values of the constants toward the values observed in cultures using glucose alone. Addition of cyclic AMP (cyclic adenosine 3':5'-monophosphate) during exponential growth of a culture using glucose caused the values of the constants to be shifted toward the values observed in cultures using a carbon source other than glucose. In all of the metabolic conditions studied in this report the adenylate energy charge ((ATP + 1/2 ADP)/(ATP + ADP + AMP)) and the level of the rate-limiting enzyme of glycogen synthesis, ADP-glucose synthetase (glucose 1-phosphate adenylyltransferase, EC 2.7.7.27), were the same. The data presented here indicate that the difference we observed in the quantitative relationship for glycogen synthesis is the result of the different cellular levels of cyclic AMP in the cells using glucose and the cells using one of the other carbon sources. Since cyclic AMP does not affect the velocity of ADP-glucose synthetase in vitro, apparently a change in the cellular level of cyclic AMP causes a shift in the cellular level of a presently unknown (and previously undetected) effector of this enzyme. The shift in the level of this effector evidently alters the response of the enzyme in vivo to the substrate glucose 1-phosphate and the activator fructose 1,6-diphosphate.", "contents": "Contribution of cyclic adenosine 3':5'-monophosphate to the regulation of bacterial glycogen synthesis in vivo. Effect of carbon source and cyclic adenosine 3':5'-monophosphate on the quantitative relationship between the rate of glycogen synthesis and the cellular concentrations of glucose 6-phosphate and fructose 1,6-diphosphate in Escherichia coli. When either fructose, glycerol, or succinate served as a sole source of carbon and energy in nitrogen-starved cultures of Escherichia coli W4597(K) the values of the kinetic constants of the equation that expresses the relationship between glycogen synthesis and hexose phosphates were different from the values observed when glucose was the sole source of carbon and energy. Addition of glucose during either exponential growth or nitrogen starvation to a culture using one of the other carbon sources slowed the rate of glycogen synthesis and shifted the values of the constants toward the values observed in cultures using glucose alone. Addition of cyclic AMP (cyclic adenosine 3':5'-monophosphate) during exponential growth of a culture using glucose caused the values of the constants to be shifted toward the values observed in cultures using a carbon source other than glucose. In all of the metabolic conditions studied in this report the adenylate energy charge ((ATP + 1/2 ADP)/(ATP + ADP + AMP)) and the level of the rate-limiting enzyme of glycogen synthesis, ADP-glucose synthetase (glucose 1-phosphate adenylyltransferase, EC 2.7.7.27), were the same. The data presented here indicate that the difference we observed in the quantitative relationship for glycogen synthesis is the result of the different cellular levels of cyclic AMP in the cells using glucose and the cells using one of the other carbon sources. Since cyclic AMP does not affect the velocity of ADP-glucose synthetase in vitro, apparently a change in the cellular level of cyclic AMP causes a shift in the cellular level of a presently unknown (and previously undetected) effector of this enzyme. The shift in the level of this effector evidently alters the response of the enzyme in vivo to the substrate glucose 1-phosphate and the activator fructose 1,6-diphosphate."}
{"id": "PMID:224053", "title": "Shedding of hyaluronate from the cell surface of Rous sarcoma virus-transformed chondrocytes.", "content": "Transformation of cultured chick embryo chondrocytes with Rous sarcoma virus gives rise to increased incorporation of isotopic precursors into hyaluronate and decreased incorporation into chondroitin 6-sulfate. Chemical measurements of these glycosaminoglycans showed corresponding changes. Comparison of the kinetics of production of glycosaminoglycan by normal and Rous sarcoma virus-transformed chondrocytes demonstrated (i) that the rate of accumulation in the medium was similar in both cultures, and (ii) that approximately 50% of total glycosaminoglycan produced by the normal chondrocytes, but only 10% of that from the transformed cells, accumulated in the cell layer. Prelabel-chase experiments indicated that cell surface-associated hyaluronate, as measured by release from the cell layer by trypsin treatment, was shed rapidly into the medium and accounted for all of the hyaluronate which accumulated in the medium. Thus we conclude (i) that accumulation of cell surface-associated glycosaminoglycan is dramatically reduced in Rous sarcoma virus-transformed chondrocytes, and (ii) that hyaluronate produced by the transformed chondrocytes is first deposited in the cell-associated extracellular compartment and then rapidly shed into the medium, rather than being secreted directly into the medium.", "contents": "Shedding of hyaluronate from the cell surface of Rous sarcoma virus-transformed chondrocytes. Transformation of cultured chick embryo chondrocytes with Rous sarcoma virus gives rise to increased incorporation of isotopic precursors into hyaluronate and decreased incorporation into chondroitin 6-sulfate. Chemical measurements of these glycosaminoglycans showed corresponding changes. Comparison of the kinetics of production of glycosaminoglycan by normal and Rous sarcoma virus-transformed chondrocytes demonstrated (i) that the rate of accumulation in the medium was similar in both cultures, and (ii) that approximately 50% of total glycosaminoglycan produced by the normal chondrocytes, but only 10% of that from the transformed cells, accumulated in the cell layer. Prelabel-chase experiments indicated that cell surface-associated hyaluronate, as measured by release from the cell layer by trypsin treatment, was shed rapidly into the medium and accounted for all of the hyaluronate which accumulated in the medium. Thus we conclude (i) that accumulation of cell surface-associated glycosaminoglycan is dramatically reduced in Rous sarcoma virus-transformed chondrocytes, and (ii) that hyaluronate produced by the transformed chondrocytes is first deposited in the cell-associated extracellular compartment and then rapidly shed into the medium, rather than being secreted directly into the medium."}
{"id": "PMID:224058", "title": "Regulation of fatty acid synthetase activity. The 4'-phosphopantetheine hydrolase of rat liver.", "content": "The 4'-phosphopantetheine hydrolase of rat liver, partially purified by ammonium sulfate precipitation, catalyzes the hydrolysis of the prosthetic group 4'-phosphopantetheine from the holo-fatty acid synthetase. The two products of the action of this enzyme, 4'-phosphopantetheine and apo-fatty acid synthetase, were isolated by DEAE-cellulose chromatography and by chromatography on a Sepharose epsilon-aminocaproyl pantetheine column, respectively. The resultant apo-fatty acid synthetase was quantitated by immunoprecipitation and it was also converted to the holoprotein with a crude preparation of rat liver 4'-phosphopantetheine transferase. Quantitative determination of the hydrolase reaction product, 4'-phosphopantetheine, by amino acid analysis and microbiological assays confirmed the presence of 1 mol of this compound/mol of holo-fatty acid synthetase.", "contents": "Regulation of fatty acid synthetase activity. The 4'-phosphopantetheine hydrolase of rat liver. The 4'-phosphopantetheine hydrolase of rat liver, partially purified by ammonium sulfate precipitation, catalyzes the hydrolysis of the prosthetic group 4'-phosphopantetheine from the holo-fatty acid synthetase. The two products of the action of this enzyme, 4'-phosphopantetheine and apo-fatty acid synthetase, were isolated by DEAE-cellulose chromatography and by chromatography on a Sepharose epsilon-aminocaproyl pantetheine column, respectively. The resultant apo-fatty acid synthetase was quantitated by immunoprecipitation and it was also converted to the holoprotein with a crude preparation of rat liver 4'-phosphopantetheine transferase. Quantitative determination of the hydrolase reaction product, 4'-phosphopantetheine, by amino acid analysis and microbiological assays confirmed the presence of 1 mol of this compound/mol of holo-fatty acid synthetase."}
{"id": "PMID:224059", "title": "The role of cyclic AMP in aldosterone production by isolated zona glomerulosa cells.", "content": "The role of cyclic AMP in the regulation of aldosterone production by adrenocorticotropic hormone (ACTH), angiotensin II (A II), potassium, and serotonin was examined in collagenase-dispersed adrenal glomerulosa cells. The ability of 8-bromo cyclic AMP and choleragen to stimulate maximum aldosterone production indicated that cyclic AMP could act as second messenger for certain of the aldosterone-stimulating factors. The actions of ACTH and choleragen on aldosterone and cyclic AMP production were correlated in dog and rat cells, and a similar relation was seen during stimulation of rat cells by serotonin. In contrast, A II and potassium did not cause changes in cyclic AMP formation while stimulating aldosterone production. Intracellular and receptor-bound cyclic AMP were increased 3-fold by 10(-7) M ACTH but not by A II. Addition of a phosphodiesterase inhibitor increased the magnitude of the cyclic AMP response to ACTH but did not change the lack of stimulation by A II or potassium. In dog cells, the effects of A II and potassium on aldosterone production were partially additive to those of ACTH, choleragen, and 8-bromo cyclic AMP. In contrast, no additivity was observed between A II and potassium, or between combinations of the cyclic AMP-dependent stimuli. These results indicate that the actions of ACTH on aldosterone secretion are mediated by cyclic AMP formation, whereas A II and potassium stimulate aldosterone production through an independent mechanism. The lack of additivity between steroid responses to A II and potassium suggests that these factors could share a common mode of action on steroidogenesis in zona glomerulosa cells.", "contents": "The role of cyclic AMP in aldosterone production by isolated zona glomerulosa cells. The role of cyclic AMP in the regulation of aldosterone production by adrenocorticotropic hormone (ACTH), angiotensin II (A II), potassium, and serotonin was examined in collagenase-dispersed adrenal glomerulosa cells. The ability of 8-bromo cyclic AMP and choleragen to stimulate maximum aldosterone production indicated that cyclic AMP could act as second messenger for certain of the aldosterone-stimulating factors. The actions of ACTH and choleragen on aldosterone and cyclic AMP production were correlated in dog and rat cells, and a similar relation was seen during stimulation of rat cells by serotonin. In contrast, A II and potassium did not cause changes in cyclic AMP formation while stimulating aldosterone production. Intracellular and receptor-bound cyclic AMP were increased 3-fold by 10(-7) M ACTH but not by A II. Addition of a phosphodiesterase inhibitor increased the magnitude of the cyclic AMP response to ACTH but did not change the lack of stimulation by A II or potassium. In dog cells, the effects of A II and potassium on aldosterone production were partially additive to those of ACTH, choleragen, and 8-bromo cyclic AMP. In contrast, no additivity was observed between A II and potassium, or between combinations of the cyclic AMP-dependent stimuli. These results indicate that the actions of ACTH on aldosterone secretion are mediated by cyclic AMP formation, whereas A II and potassium stimulate aldosterone production through an independent mechanism. The lack of additivity between steroid responses to A II and potassium suggests that these factors could share a common mode of action on steroidogenesis in zona glomerulosa cells."}
{"id": "PMID:224060", "title": "Characterization of small cAMP-binding fragments of cAMP-dependent protein kinases.", "content": "Monomeric cAMP-binding fragments of molecular mass 16,000 and 14,000 daltons were obtained by Sephadex G-75 chromatography of partially trypsin-hydrolyzed regulatory subunits of cAMP-dependent protein kinase isozymes I and II, respectively. The Stokes radii were 19.1 and 16.4 A, the frictional ratios were 1.15 and 1.03, and the sedimentation coefficients were 1.94 and 1.91 S for the 16,000- and 14,000-dalton fragments, respectively. The 16,000-dalton fragment retained specific cyclic nucleotide binding characteristics of the native protein. The specificity of cyclic nucleotide binding to the 14,000-dalton fragment (cAMP greater than cIMP = 8-bromo-cAMP = 8-oxo-cAMP greater than cUMP = cGMP) differed from that of the native subunit (cAMP = 8-oxo-cAMP greater than 8-bromo-cAMP greater than cIMP greater than cUMP = cGMP). The 14,000-dalton fragment bound nearly 1 mol of cAMP/mol of fragment. The binding exchange rate of cAMP was much faster for the 14,000-dalton fragment than for either of the native regulatory subunits or for the 16,000 dalton fragment. Although hemin inhibited cAMP binding to the native regulatory subunits and to the 16,000 dalton fragment, the molecule did not affect cAMP binding to the 14,000-dalton fragment. Both of the native regulatory subunits and the isolated 16,000- and 14,000-dalton fragments could be covalently labeled with the photoaffinity analog, 8-N3-[32P]cAMP. The 14,000-dalton fragment could not be phosphorylated and neither fragment could recombine with the catalytic subunit to inhibit its activity. The results indicate that the functional entities of the regulatory subunit other than cAMP binding are destroyed by trypsin. The properties of the 16,000-dalton fragment suggest that the intact cAMP-binding site is contained in a small trypsin-resistant \"core\" of the native regulatory subunit. The properties of the 14,000-dalton fragment imply that part of the binding site of the native regulatory subunit was slighlty modified or lost during preparation of this fragment.", "contents": "Characterization of small cAMP-binding fragments of cAMP-dependent protein kinases. Monomeric cAMP-binding fragments of molecular mass 16,000 and 14,000 daltons were obtained by Sephadex G-75 chromatography of partially trypsin-hydrolyzed regulatory subunits of cAMP-dependent protein kinase isozymes I and II, respectively. The Stokes radii were 19.1 and 16.4 A, the frictional ratios were 1.15 and 1.03, and the sedimentation coefficients were 1.94 and 1.91 S for the 16,000- and 14,000-dalton fragments, respectively. The 16,000-dalton fragment retained specific cyclic nucleotide binding characteristics of the native protein. The specificity of cyclic nucleotide binding to the 14,000-dalton fragment (cAMP greater than cIMP = 8-bromo-cAMP = 8-oxo-cAMP greater than cUMP = cGMP) differed from that of the native subunit (cAMP = 8-oxo-cAMP greater than 8-bromo-cAMP greater than cIMP greater than cUMP = cGMP). The 14,000-dalton fragment bound nearly 1 mol of cAMP/mol of fragment. The binding exchange rate of cAMP was much faster for the 14,000-dalton fragment than for either of the native regulatory subunits or for the 16,000 dalton fragment. Although hemin inhibited cAMP binding to the native regulatory subunits and to the 16,000 dalton fragment, the molecule did not affect cAMP binding to the 14,000-dalton fragment. Both of the native regulatory subunits and the isolated 16,000- and 14,000-dalton fragments could be covalently labeled with the photoaffinity analog, 8-N3-[32P]cAMP. The 14,000-dalton fragment could not be phosphorylated and neither fragment could recombine with the catalytic subunit to inhibit its activity. The results indicate that the functional entities of the regulatory subunit other than cAMP binding are destroyed by trypsin. The properties of the 16,000-dalton fragment suggest that the intact cAMP-binding site is contained in a small trypsin-resistant \"core\" of the native regulatory subunit. The properties of the 14,000-dalton fragment imply that part of the binding site of the native regulatory subunit was slighlty modified or lost during preparation of this fragment."}
{"id": "PMID:224062", "title": "Purification of a reconstitutively active iron-sulfur protein (oxidation factor) from succinate . cytochrome c reductase complex of bovine heart mitochondria.", "content": "Oxidation factor, a protein required for electron transfer from succinate to cytochrome c in the mitochondrial respiratory chain, has been purified from isolated succinate . cytochrome c reductase complex. Purification of the protein has been followed by a reconstitution assay in which restoration of ubiquinol . cytochrome c reductase activity is proportional to the amount of oxidation factor added back to depleted reductase complex. The purified protein is a homogeneous polypeptide on acrylamide gel electrophoresis in sodium dodecyl sulfate and migrates with an apparent Mr = 24,500. Purified oxidation factor restores succinate . cytochrome c reductase and ubiquinol . cytochrome c reductase activities to depleted reductase complex. It is not required for succinate dehydrogenase nor for succinate . ubiquinone reductase activities of the reconstituted reductase complex. Oxidation factor co-electrophoreses with the iron-sulfur protein polypeptide of ubiquinol . cytochrome c reductase complex. The purified protein contains 56 nmol of nonheme iron and 36 nmol of acid-labile sulfide/mg of protein and possesses an EPR spectrum with the characteristic \"g = 1.90\" signal identical to that of the iron-sulfur protein of the cytochrome b . c1 complex. In addition, the optimal conditions for extraction of oxidation factor, including reduction with hydrosulfite and treatment of the b . c1 complex with antimycin, are identical to those which facilitate extraction of the iron-sulfur protein from the b . c1 complex. These results indicate that oxidation factor is a reconstitutively active form of the iron-sulfur protein of the cytochrome b . c1 complex first discovered by Rieske and co-workers (Rieske, J.S., Maclennan, D.H., and Coleman, R. (1964) Biochem. Biophys. Res. Commun. 15, 338-344) and thus demonstrate that this iron-sulfur protein is required for electron transfer from ubiquinol to cytochrome c in the mitochondrial respiratory chain.", "contents": "Purification of a reconstitutively active iron-sulfur protein (oxidation factor) from succinate . cytochrome c reductase complex of bovine heart mitochondria. Oxidation factor, a protein required for electron transfer from succinate to cytochrome c in the mitochondrial respiratory chain, has been purified from isolated succinate . cytochrome c reductase complex. Purification of the protein has been followed by a reconstitution assay in which restoration of ubiquinol . cytochrome c reductase activity is proportional to the amount of oxidation factor added back to depleted reductase complex. The purified protein is a homogeneous polypeptide on acrylamide gel electrophoresis in sodium dodecyl sulfate and migrates with an apparent Mr = 24,500. Purified oxidation factor restores succinate . cytochrome c reductase and ubiquinol . cytochrome c reductase activities to depleted reductase complex. It is not required for succinate dehydrogenase nor for succinate . ubiquinone reductase activities of the reconstituted reductase complex. Oxidation factor co-electrophoreses with the iron-sulfur protein polypeptide of ubiquinol . cytochrome c reductase complex. The purified protein contains 56 nmol of nonheme iron and 36 nmol of acid-labile sulfide/mg of protein and possesses an EPR spectrum with the characteristic \"g = 1.90\" signal identical to that of the iron-sulfur protein of the cytochrome b . c1 complex. In addition, the optimal conditions for extraction of oxidation factor, including reduction with hydrosulfite and treatment of the b . c1 complex with antimycin, are identical to those which facilitate extraction of the iron-sulfur protein from the b . c1 complex. These results indicate that oxidation factor is a reconstitutively active form of the iron-sulfur protein of the cytochrome b . c1 complex first discovered by Rieske and co-workers (Rieske, J.S., Maclennan, D.H., and Coleman, R. (1964) Biochem. Biophys. Res. Commun. 15, 338-344) and thus demonstrate that this iron-sulfur protein is required for electron transfer from ubiquinol to cytochrome c in the mitochondrial respiratory chain."}
{"id": "PMID:224063", "title": "Pitfalls to avoid: accidental intravenous injection of Ethiodol.", "content": "Direct intravenous injection of Ethiodol occurred at lymphography. Early fluoroscopic or radiographic film evaluation, and careful monitoring of injection rates, would help to avoid this complication.", "contents": "Pitfalls to avoid: accidental intravenous injection of Ethiodol. Direct intravenous injection of Ethiodol occurred at lymphography. Early fluoroscopic or radiographic film evaluation, and careful monitoring of injection rates, would help to avoid this complication."}
{"id": "PMID:224064", "title": "Prostaglandin E2 and cyclic AMP levels in human breast tumors.", "content": "Prostaglandin E2 (PGE2) and cyclic adenosine-3', 5'-monophosphate (cAMP) concentrations were measured in human benign and malignant breast tumors by radioimmunoassay. Two groups were found among the malignant tissues, one with high PGE2 (M = 65.89 pg/mg) and high cAMP (M = 0.704 pmole/mg) concentrations and one with low concentrations (M = 9.24 pg/mg and M = 0.299 pmole/mg, respectively). The low PGE2 levels in the malignant tumors did not differ significantly from the levels found in benign tumors (M = 8.06 pg/mg). cAMP levels were positively and highly correlated (r = +0.81) with PGE2 levels. No bone osteolysis could be discovered in any of the patients a few weeks after mastectomy operation, but PGE2 analysis of breast tumors may have prognostic value for the future.", "contents": "Prostaglandin E2 and cyclic AMP levels in human breast tumors. Prostaglandin E2 (PGE2) and cyclic adenosine-3', 5'-monophosphate (cAMP) concentrations were measured in human benign and malignant breast tumors by radioimmunoassay. Two groups were found among the malignant tissues, one with high PGE2 (M = 65.89 pg/mg) and high cAMP (M = 0.704 pmole/mg) concentrations and one with low concentrations (M = 9.24 pg/mg and M = 0.299 pmole/mg, respectively). The low PGE2 levels in the malignant tumors did not differ significantly from the levels found in benign tumors (M = 8.06 pg/mg). cAMP levels were positively and highly correlated (r = +0.81) with PGE2 levels. No bone osteolysis could be discovered in any of the patients a few weeks after mastectomy operation, but PGE2 analysis of breast tumors may have prognostic value for the future."}
{"id": "PMID:224065", "title": "Light and electron microscopic investigations of nasopharyngeal carcinomas with regard to the viral etiology of these tumors.", "content": "Five carcinomata of the nasopharynx (four lymphoepithelial carcinomata of the Regaud type and one squamous cell carcinoma) were examined light and electron microscopically. In addition to the familiar histological and cytological features of these tumors, and because of an increased antibody titer against Epstein-Barr virus in all five patients, all those cytoplasmic and nuclear inclusions were examined which could be interpreted as indicative of a virus contact. The following structures were found: 1. Particles and microtubules which correspond in diameter, shape, and location to Corona viruses. 2. Particles surrounded by a double membrane and resembling in form and diameter Oncorna viruses. 3. Tubulo-reticular, coil-shaped cytoplasmic inclusions interpreted as an unspecific reaction of the host cell to viral attack. 4. Spherical nuclear bodies, which are frequently observed in tumors and in viral infections. 5. Intranuclear particles which correspond in diameter, structure, and distribution to viruses of the herpes type such as have been described in cell cultures of Burkitt lymphoma and nasopharyngeal carcinoma. The fifth group particularly was discussed in detail with regard to differentiation between those particles and other structures which could simulate a virus structure. Together with the appearance of increased ribosomes and of particular chromatin distribution within the tumor cell nuclei, the particles we discussed have been interpreted as morphological indications of a virus etiology of the examined tumors.", "contents": "Light and electron microscopic investigations of nasopharyngeal carcinomas with regard to the viral etiology of these tumors. Five carcinomata of the nasopharynx (four lymphoepithelial carcinomata of the Regaud type and one squamous cell carcinoma) were examined light and electron microscopically. In addition to the familiar histological and cytological features of these tumors, and because of an increased antibody titer against Epstein-Barr virus in all five patients, all those cytoplasmic and nuclear inclusions were examined which could be interpreted as indicative of a virus contact. The following structures were found: 1. Particles and microtubules which correspond in diameter, shape, and location to Corona viruses. 2. Particles surrounded by a double membrane and resembling in form and diameter Oncorna viruses. 3. Tubulo-reticular, coil-shaped cytoplasmic inclusions interpreted as an unspecific reaction of the host cell to viral attack. 4. Spherical nuclear bodies, which are frequently observed in tumors and in viral infections. 5. Intranuclear particles which correspond in diameter, structure, and distribution to viruses of the herpes type such as have been described in cell cultures of Burkitt lymphoma and nasopharyngeal carcinoma. The fifth group particularly was discussed in detail with regard to differentiation between those particles and other structures which could simulate a virus structure. Together with the appearance of increased ribosomes and of particular chromatin distribution within the tumor cell nuclei, the particles we discussed have been interpreted as morphological indications of a virus etiology of the examined tumors."}
{"id": "PMID:224066", "title": "Changes in mouse skin cyclic nucleotides during chemical carcinogenesis and tumor response to treatment with BCG, L-Dopa and cyclic DBAMP.", "content": "During chemical carcinogenesis by 9, 10-dimethyl 1,2-benzanthracene the cyclic AMP and GMP content was measured in the skin of mice. The tissue of the developing skin tumor is characterized by an elevated cyclic GMP- and a lowered cyclic AMP level. Consequently the quotient of cyclic AMP and GMP is greatly lowered and is discussed as a crucial factor of cell derangement. Complete regression of the tumor is to be achieved by increasing the cyclic AMP levels by means of cyclic DBAMP and L-Dopa in 20% of the experimental animals. Additional stimulation by BCG of the unspecific immune defence has a favourable effect on tumor regression (about 50%). In a different type of tumor (solid Ehrlich carcinoma) it was possible after pretreatment of the mice with L-Dopa, cyclic DBAMP and BCG and after treatment following tumor injection to prevent tumor development in 67% of the animals.", "contents": "Changes in mouse skin cyclic nucleotides during chemical carcinogenesis and tumor response to treatment with BCG, L-Dopa and cyclic DBAMP. During chemical carcinogenesis by 9, 10-dimethyl 1,2-benzanthracene the cyclic AMP and GMP content was measured in the skin of mice. The tissue of the developing skin tumor is characterized by an elevated cyclic GMP- and a lowered cyclic AMP level. Consequently the quotient of cyclic AMP and GMP is greatly lowered and is discussed as a crucial factor of cell derangement. Complete regression of the tumor is to be achieved by increasing the cyclic AMP levels by means of cyclic DBAMP and L-Dopa in 20% of the experimental animals. Additional stimulation by BCG of the unspecific immune defence has a favourable effect on tumor regression (about 50%). In a different type of tumor (solid Ehrlich carcinoma) it was possible after pretreatment of the mice with L-Dopa, cyclic DBAMP and BCG and after treatment following tumor injection to prevent tumor development in 67% of the animals."}
{"id": "PMID:224067", "title": "Establishment and characterization of C-type RNA virus-producing cell lines from radiation-induced murine osteosarcomas.", "content": "Eight cell lines were established from murine osteosarcomas induced in vivo with the radionuclides 224Ra and 227Th. They have been compared by light and electron microscopy, by karyology, and by their growth properties. The morphology, the growth pattern, and the ability to induce tumors in mice indicate that five of them are tumor cell lines. Chromosome studies demonstrated that the five cell lines have marker chromosomes. The other cell lines only showed some criteria generally used to score for transformation of fibroblasts and they may be derived from stromal cells. All cell lines release virus particles in the culture fluid which have the typical properties of RNA tumor viruses. They possess C-type morphology, a density of 1.16--1.18 g/cm3, a 60--70 S RNA, a RNA dependent DNA polymerase and they induce syncytia in rat XC cells. The possible significance of these virus particles in radiation osteosarcomagenesis is discussed.", "contents": "Establishment and characterization of C-type RNA virus-producing cell lines from radiation-induced murine osteosarcomas. Eight cell lines were established from murine osteosarcomas induced in vivo with the radionuclides 224Ra and 227Th. They have been compared by light and electron microscopy, by karyology, and by their growth properties. The morphology, the growth pattern, and the ability to induce tumors in mice indicate that five of them are tumor cell lines. Chromosome studies demonstrated that the five cell lines have marker chromosomes. The other cell lines only showed some criteria generally used to score for transformation of fibroblasts and they may be derived from stromal cells. All cell lines release virus particles in the culture fluid which have the typical properties of RNA tumor viruses. They possess C-type morphology, a density of 1.16--1.18 g/cm3, a 60--70 S RNA, a RNA dependent DNA polymerase and they induce syncytia in rat XC cells. The possible significance of these virus particles in radiation osteosarcomagenesis is discussed."}
{"id": "PMID:224068", "title": "Sodium-potassium adenosine triphosphatase activity of human lymphocyte membrane vesicles: kinetic parameters, substrate specificity, and effects of phytohemagglutinin.", "content": "We have prepared human blood lymphocyte membrane vesicles of high purity in sufficient quantity for detailed enzyme analysis. This was made possible by the use of plateletpheresis residues, which contain human lymphocytes in amounts equivalent to thousands of milliliters of blood. The substrate specificity and the kinetics of the cofactor and substrate requirements of the human lymphocyte membrane Na+, K+-ATPase activity were characterized. The Na+, K+-ATPase did not hydrolyze ADP, AMP, ITP, UTP, GTP or TTP. The mean ATPase stimulated by optimal concentrations of Na+ and K+ (Na+, K+-ATPase) was 1.5 nmol of P(i) hydrolyzed, microgram protein-1, 30 min-1 (range 0.9-2.1). This activity was completely inhibited by the cardiac glycoside, ouabain. The K(m) for K+ was approximately 1.0 mM and the K(m) for Na+ was approximately 15 mM. Active Na+ and K+ transport and ouabain-sensitive ATP production increase when lymphocytes are stimulated by PHA. Na+, K+-ATPase activity must increase also to transduce energy for the transport of Na+ and K+. Some studies have reported that PHA stimulates the lymphocyte membrane ATPase directly. We did not observe stimulation of the membrane Na+, K+-ATPase when either lymphocytes or lymphocyte membranes were treated with mitogenic concentrations of PHA. Moreover, PHA did not enhance the reaction velocity of the Na+, K+-ATPase when studied at the K(m) for ATP, Na+, K+ OR Mg++, indicating that it does not alter the affinity of the enzyme for its substrate or cofactors. Thus, our data indicate that the increase in ATPase activity does not occur as a direct result of PHA action on the cell membrane.", "contents": "Sodium-potassium adenosine triphosphatase activity of human lymphocyte membrane vesicles: kinetic parameters, substrate specificity, and effects of phytohemagglutinin. We have prepared human blood lymphocyte membrane vesicles of high purity in sufficient quantity for detailed enzyme analysis. This was made possible by the use of plateletpheresis residues, which contain human lymphocytes in amounts equivalent to thousands of milliliters of blood. The substrate specificity and the kinetics of the cofactor and substrate requirements of the human lymphocyte membrane Na+, K+-ATPase activity were characterized. The Na+, K+-ATPase did not hydrolyze ADP, AMP, ITP, UTP, GTP or TTP. The mean ATPase stimulated by optimal concentrations of Na+ and K+ (Na+, K+-ATPase) was 1.5 nmol of P(i) hydrolyzed, microgram protein-1, 30 min-1 (range 0.9-2.1). This activity was completely inhibited by the cardiac glycoside, ouabain. The K(m) for K+ was approximately 1.0 mM and the K(m) for Na+ was approximately 15 mM. Active Na+ and K+ transport and ouabain-sensitive ATP production increase when lymphocytes are stimulated by PHA. Na+, K+-ATPase activity must increase also to transduce energy for the transport of Na+ and K+. Some studies have reported that PHA stimulates the lymphocyte membrane ATPase directly. We did not observe stimulation of the membrane Na+, K+-ATPase when either lymphocytes or lymphocyte membranes were treated with mitogenic concentrations of PHA. Moreover, PHA did not enhance the reaction velocity of the Na+, K+-ATPase when studied at the K(m) for ATP, Na+, K+ OR Mg++, indicating that it does not alter the affinity of the enzyme for its substrate or cofactors. Thus, our data indicate that the increase in ATPase activity does not occur as a direct result of PHA action on the cell membrane."}
{"id": "PMID:224069", "title": "Plasma membrane phosphoproteins in normal and Rous sarcoma virus transformed chick embryo fibroblasts: characterization by in vitro phosphorylation.", "content": "Plasma membranes isolated from normal and RSV transformed chick embryo fibroblasts were phosphorylated in vitro using endogenous protein kinase and ATP (gamma32P) and the labeled phosphoproteins were analyzed by SDS-PAGE. A number of protein phosphorylation changes were observed following transformation, however in most cases they were relatively small quantitative differences. The four major changes were in proteins of 47,000, 58,000, 75,000 and 135,000 daltons. Decreased phosphorylation of the 47,000 dalton polypeptide was found in transformed cell membranes but this alteration was shown to be due to differences in cell growth rather than transformation. Increase phosphorylation of the 75,000 dalton protein was at least partially related to virus infection. However, increased phosphorylation of the 58,000 and 135,000 dalton polypeptides were entirely transformation specific.", "contents": "Plasma membrane phosphoproteins in normal and Rous sarcoma virus transformed chick embryo fibroblasts: characterization by in vitro phosphorylation. Plasma membranes isolated from normal and RSV transformed chick embryo fibroblasts were phosphorylated in vitro using endogenous protein kinase and ATP (gamma32P) and the labeled phosphoproteins were analyzed by SDS-PAGE. A number of protein phosphorylation changes were observed following transformation, however in most cases they were relatively small quantitative differences. The four major changes were in proteins of 47,000, 58,000, 75,000 and 135,000 daltons. Decreased phosphorylation of the 47,000 dalton polypeptide was found in transformed cell membranes but this alteration was shown to be due to differences in cell growth rather than transformation. Increase phosphorylation of the 75,000 dalton protein was at least partially related to virus infection. However, increased phosphorylation of the 58,000 and 135,000 dalton polypeptides were entirely transformation specific."}
{"id": "PMID:224070", "title": "Long acting cAMP analogues enhance sulfate incorporation into matrix proteoglycans and suppress cell division of fetal rat chondrocytes in monolayer culture.", "content": "The relationship between replication and the synthesis of matrix sulfated proteoglycans was investigated with fetal rat chondrocytes grown in monolayer culture. The effect of N6 O2' dibutyryl adenosine 3', 5' cyclic monophosphate (DBcAMP), adenosine 3', 5' cyclic monophosphate (cAMP), 8 Bromo adenosine 3', 5' cyclic monophosphate (8 Br-cAMP), sodium butyrate and hydroxyurea was examined. Between 0.05 and 0.5 mM DBcAMP, a dose related inhibition of cell division and stimulation of [35SO=/4] incorporation into matrix proteoglycans was demonstrated. At the higher concentrations of DBcAMP, cell division was completely inhibited and the enhancement of [35SO=/4] incorporation into matrix proteoglycans ranged between 40 and 120% (P less than 0.01). Utilizing 14C-glucosamine and photometric determination of proteoglycans with Alcian Blue, it was demonstrated that the increase in sulfate incorporation reflected enhanced accumulation of extracellular matrix. The effects of DBcAMP were mimicked by 8 Br-cAMP, suggesting they were mediated by the adenylyl cyclase system. cAMP (0.05-0.5 mM), sodium butyrate (0.1-0.5 mM) and hydroxyurea (0.5-5 mM) partially or fully inhibited cell division, but either failed or only slightly enhanced sulfate incorporation. The enhanced sulfated proteoglycan deposition promoted by DBcAMP began 8 to 12 hours after serum stimulation, its onset occurred prior to thymidine incorporation and the effect persisted for 28 hours. Determination of cell volume demonstrated an increase in size of DBcAMP treated chondrocytes between 8 to 12 hours, coincident with the onset of increased sulfate incorporation. These results are consistent with a model where matrix sulfated proteoglycan deposition by chondrocytes is mediated by intracellular cAMP levels and occurs in the G1 phase of the cell cycle.", "contents": "Long acting cAMP analogues enhance sulfate incorporation into matrix proteoglycans and suppress cell division of fetal rat chondrocytes in monolayer culture. The relationship between replication and the synthesis of matrix sulfated proteoglycans was investigated with fetal rat chondrocytes grown in monolayer culture. The effect of N6 O2' dibutyryl adenosine 3', 5' cyclic monophosphate (DBcAMP), adenosine 3', 5' cyclic monophosphate (cAMP), 8 Bromo adenosine 3', 5' cyclic monophosphate (8 Br-cAMP), sodium butyrate and hydroxyurea was examined. Between 0.05 and 0.5 mM DBcAMP, a dose related inhibition of cell division and stimulation of [35SO=/4] incorporation into matrix proteoglycans was demonstrated. At the higher concentrations of DBcAMP, cell division was completely inhibited and the enhancement of [35SO=/4] incorporation into matrix proteoglycans ranged between 40 and 120% (P less than 0.01). Utilizing 14C-glucosamine and photometric determination of proteoglycans with Alcian Blue, it was demonstrated that the increase in sulfate incorporation reflected enhanced accumulation of extracellular matrix. The effects of DBcAMP were mimicked by 8 Br-cAMP, suggesting they were mediated by the adenylyl cyclase system. cAMP (0.05-0.5 mM), sodium butyrate (0.1-0.5 mM) and hydroxyurea (0.5-5 mM) partially or fully inhibited cell division, but either failed or only slightly enhanced sulfate incorporation. The enhanced sulfated proteoglycan deposition promoted by DBcAMP began 8 to 12 hours after serum stimulation, its onset occurred prior to thymidine incorporation and the effect persisted for 28 hours. Determination of cell volume demonstrated an increase in size of DBcAMP treated chondrocytes between 8 to 12 hours, coincident with the onset of increased sulfate incorporation. These results are consistent with a model where matrix sulfated proteoglycan deposition by chondrocytes is mediated by intracellular cAMP levels and occurs in the G1 phase of the cell cycle."}
{"id": "PMID:224071", "title": "Effect of hypothalamic extract and other factors on release of adrenocorticotropin from and adenosine 3',5'-monophosphate levels in dispersed nonpituitary tumor cells.", "content": "Tumor tissues obtained from two patients with the ectopic ACTH syndrome caused by medullary carcinoma of the thyroid and malignant epithelial thymoma were dispersed by tryptic digestion and mechanical agitation. Using the isolated cells, the effects of various agents on ACTH secretion and intracellular cAMP concentrations were studied. Addition of rat median eminence extract significantly stimulated ACTH secretion and increased levels of intracellular cAMP in both cell preparations, and a dose-response relationship appeared to exist between the dose of rat median eminence extract added and either ACTH secretion or intracellular cAMP formation in the thymic tumor cells. High concentrations of calcium also produced a marked ACTH secretion in both cases. In the thymic tumor cells, norepinephrine, serotonin, and TRH were found to be effective in increasing ACTH secretion and intracellular cAMP levels, whereas biogenic amines, hypothalamic hormones, and gastrointestinal hormones did not affect hormone secretion in the thyroid tumor cells. These results suggest that a corticortropin-releasing factor-like substance(s), as yet unspecified, may play some role in stimulating ectopic ACTH secretion by certain tumors, that both intracellular cAMP and Ca++ may be involved in ectopic hormone secretion, and that the inappropriate hormonal secretory responses of some tumors to a variety of stimuli might be mediated by altered membrane receptors of the neoplastic cells.", "contents": "Effect of hypothalamic extract and other factors on release of adrenocorticotropin from and adenosine 3',5'-monophosphate levels in dispersed nonpituitary tumor cells. Tumor tissues obtained from two patients with the ectopic ACTH syndrome caused by medullary carcinoma of the thyroid and malignant epithelial thymoma were dispersed by tryptic digestion and mechanical agitation. Using the isolated cells, the effects of various agents on ACTH secretion and intracellular cAMP concentrations were studied. Addition of rat median eminence extract significantly stimulated ACTH secretion and increased levels of intracellular cAMP in both cell preparations, and a dose-response relationship appeared to exist between the dose of rat median eminence extract added and either ACTH secretion or intracellular cAMP formation in the thymic tumor cells. High concentrations of calcium also produced a marked ACTH secretion in both cases. In the thymic tumor cells, norepinephrine, serotonin, and TRH were found to be effective in increasing ACTH secretion and intracellular cAMP levels, whereas biogenic amines, hypothalamic hormones, and gastrointestinal hormones did not affect hormone secretion in the thyroid tumor cells. These results suggest that a corticortropin-releasing factor-like substance(s), as yet unspecified, may play some role in stimulating ectopic ACTH secretion by certain tumors, that both intracellular cAMP and Ca++ may be involved in ectopic hormone secretion, and that the inappropriate hormonal secretory responses of some tumors to a variety of stimuli might be mediated by altered membrane receptors of the neoplastic cells."}
{"id": "PMID:224072", "title": "An attenuated form of congenital virilizing adrenal hyperplasia.", "content": "The families of two patients with hirsutism and oligomenorrhea were studied with iv ACTH (Cortrosyn) stimulation. The parents responded with a combined incremental rise of progesterone and 17-hydroxyprogesterone greater than 6.5 ng/dl.min, a response seen in the heterozygote parents of patients with congenital virilizing adrenal hyperplasia (CVAH). One sibling in one family responded as do heterozygous subjects, while two other siblings responded normally. The abnormal response of the two pairs of parents and the sibling along with the pattern of steroid secretion observed in the propositi suggest that the so-called adult-onset CVAH is a mild form of the homozygous state of CVAH.", "contents": "An attenuated form of congenital virilizing adrenal hyperplasia. The families of two patients with hirsutism and oligomenorrhea were studied with iv ACTH (Cortrosyn) stimulation. The parents responded with a combined incremental rise of progesterone and 17-hydroxyprogesterone greater than 6.5 ng/dl.min, a response seen in the heterozygote parents of patients with congenital virilizing adrenal hyperplasia (CVAH). One sibling in one family responded as do heterozygous subjects, while two other siblings responded normally. The abnormal response of the two pairs of parents and the sibling along with the pattern of steroid secretion observed in the propositi suggest that the so-called adult-onset CVAH is a mild form of the homozygous state of CVAH."}
{"id": "PMID:224073", "title": "Plasma levels of adrenocorticotropin and cortisol in women receiving oral contraceptive steroid treatment.", "content": "The secretion rate and plasma concentration of the adrenocortical steroid cortisol is modified in subjects treated with estrogenic and/or progestational steroids. The effects of contraceptive steroids on the secretion of ACTH are poorly documented, however, In the current investigation, we found that concentrations of ACTH and cortisol in plasma obtained at 0800--0900 h from a group of women with normal cyclic menses (n = 4) ranged from 78--120 pg/ml and 77--137 ng/ml, respectively. Although significant cyclic changes in the plasma levels of LH, FSH, 17 beta-estradiol, and progesterone occurred during the ovarian cycle, no obvious cyclic fluctuations in plasma levels of ACTH or cortisol were observed. In women treated with Norinyl 1 + 80 (1.0 mg norethindrone plus 0.08 mg mestranol), plasma concentrations of LH, FSH, 17 beta-estradiol, and progesterone were significantly lower (P less than 0.001) than plasma levels of these hormones in normal women during the ovarian cycle. The mean daily plasma concentrations of ACTH were significantly lower (P less than 0.001), whereas plasma cortisol levels were significantly higher (P less than 0.001) in women treated with oral contraceptive steroids compared to the levels of these hormones in the untreated ovulatory women.", "contents": "Plasma levels of adrenocorticotropin and cortisol in women receiving oral contraceptive steroid treatment. The secretion rate and plasma concentration of the adrenocortical steroid cortisol is modified in subjects treated with estrogenic and/or progestational steroids. The effects of contraceptive steroids on the secretion of ACTH are poorly documented, however, In the current investigation, we found that concentrations of ACTH and cortisol in plasma obtained at 0800--0900 h from a group of women with normal cyclic menses (n = 4) ranged from 78--120 pg/ml and 77--137 ng/ml, respectively. Although significant cyclic changes in the plasma levels of LH, FSH, 17 beta-estradiol, and progesterone occurred during the ovarian cycle, no obvious cyclic fluctuations in plasma levels of ACTH or cortisol were observed. In women treated with Norinyl 1 + 80 (1.0 mg norethindrone plus 0.08 mg mestranol), plasma concentrations of LH, FSH, 17 beta-estradiol, and progesterone were significantly lower (P less than 0.001) than plasma levels of these hormones in normal women during the ovarian cycle. The mean daily plasma concentrations of ACTH were significantly lower (P less than 0.001), whereas plasma cortisol levels were significantly higher (P less than 0.001) in women treated with oral contraceptive steroids compared to the levels of these hormones in the untreated ovulatory women."}
{"id": "PMID:224075", "title": "Adrenocorticotropin-dependent virilizing paraovarian tumors in Nelson's syndrome.", "content": "A 35-yr-old woman with Nelson's syndrome presented with amenorrhea and virilization. Serum testosterone (T) concentration was 605 ng/dl and fell to 33 ng/dl when dexamethasone was administered. The MCR of T fell from 1383 to 991 liters/day and the T production rate decreased by 96%. With administration of synthetic ACTH, T concentration rose to 338 ng/dl. Plasma ACTH concentration paralleled T during repeated suppression testing, suggesting that T secretion was dependent on ACTH hypersecretion. Preoperative and intraoperative ovarian vein catheterization suggested that the predominant source of androgen production was from the right ovarian vein. Laporatomy revealed multiple paraovarian tumors in the right mesosalpinyx and mesovarium. Incubation of tumor slices and ovarian tissue with [3H]pregnenolone and [14C]17-hydroxyprogesterone demonstrated conversion of both precursors to T by the tumor and confirmed that the tumors were the source of androgen excess. The microscopic appearance of the tumors closely resembled the morphology of testicular and paratesticular tumors of men with congenital adrenal hyperplasia and Nelson's syndrome. The analogous dependency of the tumors on ACTH hypersecretion in men with paratesticular tumors and in this woman with paraovarian tumors suggests that the tumors may arise in both males and females from a common steroid-secreting cell of adrenogenital origin.", "contents": "Adrenocorticotropin-dependent virilizing paraovarian tumors in Nelson's syndrome. A 35-yr-old woman with Nelson's syndrome presented with amenorrhea and virilization. Serum testosterone (T) concentration was 605 ng/dl and fell to 33 ng/dl when dexamethasone was administered. The MCR of T fell from 1383 to 991 liters/day and the T production rate decreased by 96%. With administration of synthetic ACTH, T concentration rose to 338 ng/dl. Plasma ACTH concentration paralleled T during repeated suppression testing, suggesting that T secretion was dependent on ACTH hypersecretion. Preoperative and intraoperative ovarian vein catheterization suggested that the predominant source of androgen production was from the right ovarian vein. Laporatomy revealed multiple paraovarian tumors in the right mesosalpinyx and mesovarium. Incubation of tumor slices and ovarian tissue with [3H]pregnenolone and [14C]17-hydroxyprogesterone demonstrated conversion of both precursors to T by the tumor and confirmed that the tumors were the source of androgen excess. The microscopic appearance of the tumors closely resembled the morphology of testicular and paratesticular tumors of men with congenital adrenal hyperplasia and Nelson's syndrome. The analogous dependency of the tumors on ACTH hypersecretion in men with paratesticular tumors and in this woman with paraovarian tumors suggests that the tumors may arise in both males and females from a common steroid-secreting cell of adrenogenital origin."}
{"id": "PMID:224076", "title": "ACTH, beta-LPH and beta-endorphin in pituitary adenomas of the patients with Cushing's disease: activation of beta-LPH conversion to beta-endorphin.", "content": "ACTH, beta-lipotropin (beta-LPH) and beta-endorphin concentrations were determined in pituitary adenomas of the patients with Cushing's disease. Immunoreactive ACTH and beta-endorphin were present in high concentrations and essentially equimolar amounts in pituitary adenomas. beta-LPH conversion to beta-endorphin was activated in pituitaries associated with ACTH/beta-LPH producing adenomas. Immunoreactive ACTH and beta-endorphin concentrations were markedly suppressed in the surrounding tissues.", "contents": "ACTH, beta-LPH and beta-endorphin in pituitary adenomas of the patients with Cushing's disease: activation of beta-LPH conversion to beta-endorphin. ACTH, beta-lipotropin (beta-LPH) and beta-endorphin concentrations were determined in pituitary adenomas of the patients with Cushing's disease. Immunoreactive ACTH and beta-endorphin were present in high concentrations and essentially equimolar amounts in pituitary adenomas. beta-LPH conversion to beta-endorphin was activated in pituitaries associated with ACTH/beta-LPH producing adenomas. Immunoreactive ACTH and beta-endorphin concentrations were markedly suppressed in the surrounding tissues."}
{"id": "PMID:224077", "title": "Altered metabolism (in vivo and in vitro) of plasma lipoproteins after selective chemical modification of lysine residues of the apoproteins.", "content": "Chemical modification of lysine residues by acetoacetylation of the apoproteins of iodinated canine and human low density lipoproteins (LDL) and canine high density lipoproteins (HDL) resulted in a marked acceleration in the rate of removal of these lipoproteins from the plasma after intravenous injection into dogs. Clearance of the lipoproteins from the plasma correlated with their rapid appearance in the liver. Acetoacetylated canine (125)I-LDL (30-60% of the lysine residues modified) were essentially completely removed from the plasma within an hour, and > 75% of the activity cleared within 5 min. Reversal of the acetoacetylation of the lysine residues of the LDL restored to these lipoproteins a rate of clearance essentially identical to that of control LDL. Identical results were obtained with modified human LDL injected into dogs. At 10 min, when congruent with 90% of the acetoacetylated human (125)I-LDL had been removed from the plasma, 90% of the total injected activity could be accounted for in the liver. Furthermore, it was possible to demonstrate an enhancement in uptake and degradation of acetoacetylated LDL by canine peritoneal macrophages in vitro. The mechanism(s) responsible for the enhanced removal of the LDL and HDL in vivo and in vitro remains to be determined. By contrast, however, acetoacetylation of canine (125)I-apoE HDL(c) did not accelerate their rate of removal from the plasma but, in fact, retarded their clearance. Control (native) apoE HDL(c) were removed from the plasma (64% within 20 min) and rapidly appeared in the liver (39% at 20 min). At the same time point, only 45% of the acetoacetylated apoE HDL(c) were cleared from the plasma and <10% appeared in the liver. Acetoacetylation of the apoE HDL(c) did not enhance their uptake or degradation by macrophages. The rapid clearance from the plasma of the native apoE HDL(c) in normal and hypercholesterolemic dogs suggests that the liver may be a normal site for the removal of the cholesteryl ester-rich apoE HDL(c). The retardation in removal after acetoacetylation of apoE HDL(c) indicates that the uptake process may be mediated by a lysine-dependent recognition system.", "contents": "Altered metabolism (in vivo and in vitro) of plasma lipoproteins after selective chemical modification of lysine residues of the apoproteins. Chemical modification of lysine residues by acetoacetylation of the apoproteins of iodinated canine and human low density lipoproteins (LDL) and canine high density lipoproteins (HDL) resulted in a marked acceleration in the rate of removal of these lipoproteins from the plasma after intravenous injection into dogs. Clearance of the lipoproteins from the plasma correlated with their rapid appearance in the liver. Acetoacetylated canine (125)I-LDL (30-60% of the lysine residues modified) were essentially completely removed from the plasma within an hour, and > 75% of the activity cleared within 5 min. Reversal of the acetoacetylation of the lysine residues of the LDL restored to these lipoproteins a rate of clearance essentially identical to that of control LDL. Identical results were obtained with modified human LDL injected into dogs. At 10 min, when congruent with 90% of the acetoacetylated human (125)I-LDL had been removed from the plasma, 90% of the total injected activity could be accounted for in the liver. Furthermore, it was possible to demonstrate an enhancement in uptake and degradation of acetoacetylated LDL by canine peritoneal macrophages in vitro. The mechanism(s) responsible for the enhanced removal of the LDL and HDL in vivo and in vitro remains to be determined. By contrast, however, acetoacetylation of canine (125)I-apoE HDL(c) did not accelerate their rate of removal from the plasma but, in fact, retarded their clearance. Control (native) apoE HDL(c) were removed from the plasma (64% within 20 min) and rapidly appeared in the liver (39% at 20 min). At the same time point, only 45% of the acetoacetylated apoE HDL(c) were cleared from the plasma and <10% appeared in the liver. Acetoacetylation of the apoE HDL(c) did not enhance their uptake or degradation by macrophages. The rapid clearance from the plasma of the native apoE HDL(c) in normal and hypercholesterolemic dogs suggests that the liver may be a normal site for the removal of the cholesteryl ester-rich apoE HDL(c). The retardation in removal after acetoacetylation of apoE HDL(c) indicates that the uptake process may be mediated by a lysine-dependent recognition system."}
{"id": "PMID:224078", "title": "Regulation of sodium and potassium transport in phytohemagglutinin-stimulated human blood lymphocytes.", "content": "Phytohemagglutinin (PHA) or concanavalin A treatment of lymphocytes causes an increase in membrane permeability so that the leak rates of Na and K increase 1.5- to 2-fold. Active Na and K transport increase proportionately in response to the increased membrane permeability. We have examined the role of lymphocyte Na concentration in sustaining the increased Na and K transport observed after PHA treatment. Cell Na concentration increases from 14.8 to 20.5 mmol/liter cell water in PHA-treated lymphocytes (P < 0.001). Four lines of evidence suggest that the 5-6 mmol/liter cell water increase in lymphocyte Na accounts for the increase in active Na and K transport in mitogen-treated lymphocytes. First, PHA does not increase directly the maximal Na, K-ATPase activity of isolated lymphocyte membrane vesicles. Second, when the Na concentration is increased by 6 mmol/liter cell water in unstimulated lymphocytes, Na and K transport increase nearly twofold. Third, the cell Na concentration (15 mmol/liter cell water) is near the K(m) for Na activation of the Na, K-ATPase in lymphocyte membranes. The ATPase activity thus, is capable of increasing as the cell Na rises above normal. Fourth, if lymphocytes are incubated in a medium containing a low Na concentration, K transport does not maintain the internal K concentration and the fall in cell K is accentuated in PHA-treated lymphocytes. These studies indicate that the adaptive acceleration of Na and K transport in mitogen-treated lymphocytes is mediated by a small increase in cell Na.", "contents": "Regulation of sodium and potassium transport in phytohemagglutinin-stimulated human blood lymphocytes. Phytohemagglutinin (PHA) or concanavalin A treatment of lymphocytes causes an increase in membrane permeability so that the leak rates of Na and K increase 1.5- to 2-fold. Active Na and K transport increase proportionately in response to the increased membrane permeability. We have examined the role of lymphocyte Na concentration in sustaining the increased Na and K transport observed after PHA treatment. Cell Na concentration increases from 14.8 to 20.5 mmol/liter cell water in PHA-treated lymphocytes (P < 0.001). Four lines of evidence suggest that the 5-6 mmol/liter cell water increase in lymphocyte Na accounts for the increase in active Na and K transport in mitogen-treated lymphocytes. First, PHA does not increase directly the maximal Na, K-ATPase activity of isolated lymphocyte membrane vesicles. Second, when the Na concentration is increased by 6 mmol/liter cell water in unstimulated lymphocytes, Na and K transport increase nearly twofold. Third, the cell Na concentration (15 mmol/liter cell water) is near the K(m) for Na activation of the Na, K-ATPase in lymphocyte membranes. The ATPase activity thus, is capable of increasing as the cell Na rises above normal. Fourth, if lymphocytes are incubated in a medium containing a low Na concentration, K transport does not maintain the internal K concentration and the fall in cell K is accentuated in PHA-treated lymphocytes. These studies indicate that the adaptive acceleration of Na and K transport in mitogen-treated lymphocytes is mediated by a small increase in cell Na."}
{"id": "PMID:224080", "title": "A simple biological method for detecting streptococcal nicotinamide adenine dinucleotide glycohydrolase.", "content": "A biological method for detecting streptococcal nicotinamide adenine dinucleotide glycohydrolase (NADG) is presented, based on its ability to inhibit the growth of Haemophilus parainfluenzae. Three hundred clinical isolates of beta-haemolytic streptococci were tested. All isolates producing NADG belonged to Lancefield's group A, C, or G.", "contents": "A simple biological method for detecting streptococcal nicotinamide adenine dinucleotide glycohydrolase. A biological method for detecting streptococcal nicotinamide adenine dinucleotide glycohydrolase (NADG) is presented, based on its ability to inhibit the growth of Haemophilus parainfluenzae. Three hundred clinical isolates of beta-haemolytic streptococci were tested. All isolates producing NADG belonged to Lancefield's group A, C, or G."}
{"id": "PMID:224081", "title": "Bone metastases in children presenting with renal tumours.", "content": "A survey of bone metastases in 132 children presenting with renal tumours has been carried out using material from the Manchester (England) Children's Tumour Registry during the period 1954 to 1976. Seven such cases were found. Only one of the 117 Wilms' tumours developed bone metastases. The remainder included carcinoma (1/4), 'bone metastasising renal tumour of childhood' (2/3), atypical tumours (2/2), and lymphosarcoma (1/1). Bone metastases from true nephroblastoma seem to be an exceptional finding.", "contents": "Bone metastases in children presenting with renal tumours. A survey of bone metastases in 132 children presenting with renal tumours has been carried out using material from the Manchester (England) Children's Tumour Registry during the period 1954 to 1976. Seven such cases were found. Only one of the 117 Wilms' tumours developed bone metastases. The remainder included carcinoma (1/4), 'bone metastasising renal tumour of childhood' (2/3), atypical tumours (2/2), and lymphosarcoma (1/1). Bone metastases from true nephroblastoma seem to be an exceptional finding."}
{"id": "PMID:224082", "title": "Angiofibromas in tuberous sclerosis: a light and electron microscopic study.", "content": "Angiofibromas from two patients with tuberous sclerosis were studied by light and electron microscopy. Light microscopy revealed that these tumor-like nodules (which in the past have been called adenoma sebaceum) were made up of dilated capillaries, venules and arterioles embedded in connective tissue. At the ultrastructural level the arterioles embedded in connective tissue. At the ultrastructural level the endothelium of these vessels showed large numbers of microvilli on their luminal surface. The stroma contained many banded structures (so-called fibrous long spacing collagen). Myofibroblasts recently described in juvenile nasopharyngeal angiofibromas were not found in these angiofibromas of tuberous sclerosis.", "contents": "Angiofibromas in tuberous sclerosis: a light and electron microscopic study. Angiofibromas from two patients with tuberous sclerosis were studied by light and electron microscopy. Light microscopy revealed that these tumor-like nodules (which in the past have been called adenoma sebaceum) were made up of dilated capillaries, venules and arterioles embedded in connective tissue. At the ultrastructural level the arterioles embedded in connective tissue. At the ultrastructural level the endothelium of these vessels showed large numbers of microvilli on their luminal surface. The stroma contained many banded structures (so-called fibrous long spacing collagen). Myofibroblasts recently described in juvenile nasopharyngeal angiofibromas were not found in these angiofibromas of tuberous sclerosis."}
{"id": "PMID:224083", "title": "The relative caries-inhibiting effects of a stannous fluoride dentifrice in a silica gel base.", "content": "An unsupervised toothbrushing study involving 1,339 children from 5 to 13 years of age conducted for three years compared two stannous fluoride dentifrices, one in a calcium pyrophosphate base and the other in a silica gel base, with a nonfluoride control dentifrice. The test dentifrice, stannous fluoride in a silica gel base, reduced caries to a significant extent when compared with the nonfluoride control dentifrice.The percentage of reductions ranged from 15% to 25% for whole mouth and interproximal surface indexes. There was no significant difference between the two fluoride dentifrices.", "contents": "The relative caries-inhibiting effects of a stannous fluoride dentifrice in a silica gel base. An unsupervised toothbrushing study involving 1,339 children from 5 to 13 years of age conducted for three years compared two stannous fluoride dentifrices, one in a calcium pyrophosphate base and the other in a silica gel base, with a nonfluoride control dentifrice. The test dentifrice, stannous fluoride in a silica gel base, reduced caries to a significant extent when compared with the nonfluoride control dentifrice.The percentage of reductions ranged from 15% to 25% for whole mouth and interproximal surface indexes. There was no significant difference between the two fluoride dentifrices."}
{"id": "PMID:224084", "title": "Simultaneous development of autoimmune disease and malignancy in two elderly patients.", "content": "Two elderly patients who presented with symptoms of \"systemic rheumatic or autoimmune disease\" had high serum titers of fluorescent antinuclear antibody (ANA). Signs of malignancy were evident at the time of the first examination. T-cell dysfunction in the aged may permit the simultaneous development of autoimmunity and neoplasia. When rheumatic symptoms with a high titer of fluorescent ANA develop in elderly patients, an exhaustive search for malignancy should be considered.", "contents": "Simultaneous development of autoimmune disease and malignancy in two elderly patients. Two elderly patients who presented with symptoms of \"systemic rheumatic or autoimmune disease\" had high serum titers of fluorescent antinuclear antibody (ANA). Signs of malignancy were evident at the time of the first examination. T-cell dysfunction in the aged may permit the simultaneous development of autoimmunity and neoplasia. When rheumatic symptoms with a high titer of fluorescent ANA develop in elderly patients, an exhaustive search for malignancy should be considered."}
{"id": "PMID:224085", "title": "Studies on the origin of the methylsulfonyl-containing metabolites from propachlor.", "content": "Metabolites in which the chlorine from propachlor has been replaced by a cysteine group or a methylsulfonyl group [-S(O2) CH3] are present in the urine of rats dosed orally with propachlor. In the present study, urine from rats given single oral doses of 35S-labeled cysteine conjugate of propachlor contained metabolites having the methylsulfonyl groups labeled with 35S. No metabolites containing 14C-labeled methylsulfonyl groups were isolated from urine of rats given single oral doses of the cysteine conjugate of propachlor in which the cysteine group was uniformly labeled with 14C. These findings show that the cysteine conjugate of propachlor is the source of sulfur in the methylsulfonyl-containing metabolites. Therefore, we suggest that a C-S lyase present in the animal cleaves the cysteine conjugate of propachlor and thus allows further metabolism of the sulfur to a methylsulfonyl moiety.", "contents": "Studies on the origin of the methylsulfonyl-containing metabolites from propachlor. Metabolites in which the chlorine from propachlor has been replaced by a cysteine group or a methylsulfonyl group [-S(O2) CH3] are present in the urine of rats dosed orally with propachlor. In the present study, urine from rats given single oral doses of 35S-labeled cysteine conjugate of propachlor contained metabolites having the methylsulfonyl groups labeled with 35S. No metabolites containing 14C-labeled methylsulfonyl groups were isolated from urine of rats given single oral doses of the cysteine conjugate of propachlor in which the cysteine group was uniformly labeled with 14C. These findings show that the cysteine conjugate of propachlor is the source of sulfur in the methylsulfonyl-containing metabolites. Therefore, we suggest that a C-S lyase present in the animal cleaves the cysteine conjugate of propachlor and thus allows further metabolism of the sulfur to a methylsulfonyl moiety."}
{"id": "PMID:224086", "title": "Ion movements in the nervous system of the American cockroach, Periplaneta americana (L.), influenced by toxaphene.", "content": "The effect of toxaphene upon ion fluxes of the central nervous system (CNS) of the cockroach, Periplaneta americana (L.), was studied in vitro. The CNS, divided into three sections (brain, thoracic, and abdominal), was exposed to 10(-5) M toxaphene in saline containing 24Na+, 42K+, 36CL-, or 45Ca++. Uptake and efflux of these ion were evaluated. Toxaphene was responsible for significant increases in the internal levels of 42K+ and 45Ca++, but had little effect upon 24Na+ or 36Cl- movements. The resulting concentration changes of the ions may be involved in the neural activity observed with toxaphene poisoning. Of the three CNS sections, significant changes were more numerous and occurred earlier in abdominal sections.", "contents": "Ion movements in the nervous system of the American cockroach, Periplaneta americana (L.), influenced by toxaphene. The effect of toxaphene upon ion fluxes of the central nervous system (CNS) of the cockroach, Periplaneta americana (L.), was studied in vitro. The CNS, divided into three sections (brain, thoracic, and abdominal), was exposed to 10(-5) M toxaphene in saline containing 24Na+, 42K+, 36CL-, or 45Ca++. Uptake and efflux of these ion were evaluated. Toxaphene was responsible for significant increases in the internal levels of 42K+ and 45Ca++, but had little effect upon 24Na+ or 36Cl- movements. The resulting concentration changes of the ions may be involved in the neural activity observed with toxaphene poisoning. Of the three CNS sections, significant changes were more numerous and occurred earlier in abdominal sections."}
{"id": "PMID:224087", "title": "Adenosine triphosphatase activities in brain, kidney and liver of mice treated with toxaphene.", "content": "The sensitivity of Na+-K+ and Mg++ Adenosine Triphosphatases (ATPases) in mouse tissues to toxaphene, a highly chlorinated camphene, was determined both in vivo and in vitro. The brain and kidney Na+-K+ ATPase activities were significantly inhibited in vitro by toxaphene. Interestingly, the inhibition was not significantly increased with an increase in the concentration of toxaphene. The oligomycin-sensitive (mitochondrial Mg++ ATPase activities in mouse brain, kidney and liver fractions were significantly inhibited by toxaphene in a concentration-dependent fashion. The oligomycin-insensitive Mg++ ATPase in all tissues examined was also inhibited but less sensitive to toxaphene than mitochondrial Mg++ ATPase. In contrast to in vitro response, the brain ATPases were not altered in mice fed toxaphene by oral intubation for three days. The renal and hepatic ATPase activities were significantly decreased in toxaphene treated mice with the oligomycin-insensitive Mg++ ATPase activity being only slightly altered.", "contents": "Adenosine triphosphatase activities in brain, kidney and liver of mice treated with toxaphene. The sensitivity of Na+-K+ and Mg++ Adenosine Triphosphatases (ATPases) in mouse tissues to toxaphene, a highly chlorinated camphene, was determined both in vivo and in vitro. The brain and kidney Na+-K+ ATPase activities were significantly inhibited in vitro by toxaphene. Interestingly, the inhibition was not significantly increased with an increase in the concentration of toxaphene. The oligomycin-sensitive (mitochondrial Mg++ ATPase activities in mouse brain, kidney and liver fractions were significantly inhibited by toxaphene in a concentration-dependent fashion. The oligomycin-insensitive Mg++ ATPase in all tissues examined was also inhibited but less sensitive to toxaphene than mitochondrial Mg++ ATPase. In contrast to in vitro response, the brain ATPases were not altered in mice fed toxaphene by oral intubation for three days. The renal and hepatic ATPase activities were significantly decreased in toxaphene treated mice with the oligomycin-insensitive Mg++ ATPase activity being only slightly altered."}
{"id": "PMID:224089", "title": "Deformities of the hand and wrist with ulnar deficiency.", "content": "Deformities of the hand and wrist in 26 upper limbs of 20 patients with ulnar deficiency were studied. In eight limbs the ulna was totally absent. In the remainder it was severely or moderately hypoplastic. Abnormalities of the digits were present in all affected limbs. There was ectrodactyly in 25 hands. The thumb was hypoplastic in 21 hands and totally absent in five. Digital deformities also included syndactyly (14 hands) and delta phalanx (six hands). Early syndactyly release, pollicization, and rotational osteotomy of the metacarpals improved hand function in many of these patients. In only three of 26 limbs was there more than 20 degrees of fixed ulnar deviation at the wrist. In 16 patients the distal ulnar \"anlage\" was not removed. None of these patients developed ulnar deviation of the wrist or progressive deformity at the wrist during growth. Resection of the distal ulnar \"anlage\" does not appear to be warranted, unless there is progressive deformity of the wrist or elbow or increased bowing of the radius.", "contents": "Deformities of the hand and wrist with ulnar deficiency. Deformities of the hand and wrist in 26 upper limbs of 20 patients with ulnar deficiency were studied. In eight limbs the ulna was totally absent. In the remainder it was severely or moderately hypoplastic. Abnormalities of the digits were present in all affected limbs. There was ectrodactyly in 25 hands. The thumb was hypoplastic in 21 hands and totally absent in five. Digital deformities also included syndactyly (14 hands) and delta phalanx (six hands). Early syndactyly release, pollicization, and rotational osteotomy of the metacarpals improved hand function in many of these patients. In only three of 26 limbs was there more than 20 degrees of fixed ulnar deviation at the wrist. In 16 patients the distal ulnar \"anlage\" was not removed. None of these patients developed ulnar deviation of the wrist or progressive deformity at the wrist during growth. Resection of the distal ulnar \"anlage\" does not appear to be warranted, unless there is progressive deformity of the wrist or elbow or increased bowing of the radius."}
{"id": "PMID:224090", "title": "Multiple digital glomus tumors.", "content": "In 28 patients with glomus tumors of the digits, 21 were relieved of symptoms by excision of a solitary tumor. Seven other patients had multiple tumors, four of which were the cause of recurrent symptoms. Three patients had multiple tumors--five in one patient, four in another, and two in a third, which had been found at the time of the first operation. A 25% incidence of multiple tumors and a 15% incidence of recurrent symptoms indicates that a careful search should be made for additional tumors.", "contents": "Multiple digital glomus tumors. In 28 patients with glomus tumors of the digits, 21 were relieved of symptoms by excision of a solitary tumor. Seven other patients had multiple tumors, four of which were the cause of recurrent symptoms. Three patients had multiple tumors--five in one patient, four in another, and two in a third, which had been found at the time of the first operation. A 25% incidence of multiple tumors and a 15% incidence of recurrent symptoms indicates that a careful search should be made for additional tumors."}
{"id": "PMID:224105", "title": "Sero-epidemiology of type--2 (genital) herpes simplex virus infection in Ibadan.", "content": "Herpes Type 1 (HT-1) virus infection is prevalent in Ibadan, Nigeria. In a study to determine the prevalence of Herpes Type-2 (HT-2) virus infection in this environment by the complement fixation (CF) test, it was shown that antibodies to the virus were not found below the age of 14 years, after which there was a gradual rise from the 16-25-year age group to a peak in the 26-35-year age group. It was suggested that the pattern of distribution of HT-2 antibodies is compatible with the sexual habits of the different age groups, and is in support of the venereal mode of transmission of the virus.", "contents": "Sero-epidemiology of type--2 (genital) herpes simplex virus infection in Ibadan. Herpes Type 1 (HT-1) virus infection is prevalent in Ibadan, Nigeria. In a study to determine the prevalence of Herpes Type-2 (HT-2) virus infection in this environment by the complement fixation (CF) test, it was shown that antibodies to the virus were not found below the age of 14 years, after which there was a gradual rise from the 16-25-year age group to a peak in the 26-35-year age group. It was suggested that the pattern of distribution of HT-2 antibodies is compatible with the sexual habits of the different age groups, and is in support of the venereal mode of transmission of the virus."}
{"id": "PMID:224107", "title": "Suggestive evidence for receptors for morphine and methionine-enkephalin on normal human blood T lymphocytes.", "content": "This study reports the in vitro influence of morphine, dextromoramide, levomoramide, and methionine-enkephalin upon normal human T blood lymphocytes by using the active and total rosette tests. Morphine and dextromoramide inhibited the percentage of active T rosettes. This effect was completely reversed in the presence of naloxone, their specific antagonist. The specificity was further demonstrated by the absence of the effect of levomoramide, the inactive enantiomere, upon the rosette system. Methionine-enkephalin increased the percentage of active T rosettes. This effect was specifically inhibited by naloxone. These observations suggest that normal human blood T lymphocytes bear surface receptor-like structures for morphine, dextromoramide, and methionine-enkephalin. Such findings may provide a link between the central nervous system and the immune system.", "contents": "Suggestive evidence for receptors for morphine and methionine-enkephalin on normal human blood T lymphocytes. This study reports the in vitro influence of morphine, dextromoramide, levomoramide, and methionine-enkephalin upon normal human T blood lymphocytes by using the active and total rosette tests. Morphine and dextromoramide inhibited the percentage of active T rosettes. This effect was completely reversed in the presence of naloxone, their specific antagonist. The specificity was further demonstrated by the absence of the effect of levomoramide, the inactive enantiomere, upon the rosette system. Methionine-enkephalin increased the percentage of active T rosettes. This effect was specifically inhibited by naloxone. These observations suggest that normal human blood T lymphocytes bear surface receptor-like structures for morphine, dextromoramide, and methionine-enkephalin. Such findings may provide a link between the central nervous system and the immune system."}
{"id": "PMID:224109", "title": "Macrophage restriction of Marek's disease virus replication and lymphoma cell proliferation.", "content": "Macrophages are shown to restrict the replication of Marek's disease virus (MDV) and isotope uptake by spleen cells from chickens bearing Marek's disease (MD) tumors. The titer of virus from duck embryo fibroblasts (DEF) co-cultivation with MDV-spleen cells pretreated to deplete marcophages was 4- to 18-fold higher than with untreated cells. Treated MDV-spleen cells increased isotope uptake by 2-fold. These restrictive activities are attributable to macrophage regulation of cell proliferation.", "contents": "Macrophage restriction of Marek's disease virus replication and lymphoma cell proliferation. Macrophages are shown to restrict the replication of Marek's disease virus (MDV) and isotope uptake by spleen cells from chickens bearing Marek's disease (MD) tumors. The titer of virus from duck embryo fibroblasts (DEF) co-cultivation with MDV-spleen cells pretreated to deplete marcophages was 4- to 18-fold higher than with untreated cells. Treated MDV-spleen cells increased isotope uptake by 2-fold. These restrictive activities are attributable to macrophage regulation of cell proliferation."}
{"id": "PMID:224112", "title": "Colloidal silica--aluminum modified--PVP density gradient centrifugation: centrifuge tube wall cell adherence, aggregation, separation properties and comparison to BSA and Ficoll.", "content": "A method is described for the inexpensive and easy preparation of colloidal silica--aluminum modified--polyvinylpyrrolidone (CS-AM-PVP) density gradient centrifugation medium. Using density gradient centrifugation, several cell separation and biochemical characteristics were studied: centrifuge tube wall cell adherence, mouse spleen cell density distribution, rebanding properties, mitogen response and cell aggregation. Cell adherence to the centrifuge tube wall using density gradients of CS-AM-PVP was compared with density gradients of bovine serum albumin and Ficoll. Few cells adhered to the centrifuge tube wall when CS-AM-PVP was used as a gradient medium; whereas, significant cell adherence to the centrifuge tube cell wall occurred when bovine serum albumin or Ficoll was used as a gradient medium. The CS-AM-PVP gradient medium did not inhibit the response to mitogens of mouse spleen cells which had been separated into density subpopulations in a discontinuous CS-AM-PVP density gradient, caused a minimum amount of cell aggregation, and was found to be non-toxic.", "contents": "Colloidal silica--aluminum modified--PVP density gradient centrifugation: centrifuge tube wall cell adherence, aggregation, separation properties and comparison to BSA and Ficoll. A method is described for the inexpensive and easy preparation of colloidal silica--aluminum modified--polyvinylpyrrolidone (CS-AM-PVP) density gradient centrifugation medium. Using density gradient centrifugation, several cell separation and biochemical characteristics were studied: centrifuge tube wall cell adherence, mouse spleen cell density distribution, rebanding properties, mitogen response and cell aggregation. Cell adherence to the centrifuge tube wall using density gradients of CS-AM-PVP was compared with density gradients of bovine serum albumin and Ficoll. Few cells adhered to the centrifuge tube wall when CS-AM-PVP was used as a gradient medium; whereas, significant cell adherence to the centrifuge tube cell wall occurred when bovine serum albumin or Ficoll was used as a gradient medium. The CS-AM-PVP gradient medium did not inhibit the response to mitogens of mouse spleen cells which had been separated into density subpopulations in a discontinuous CS-AM-PVP density gradient, caused a minimum amount of cell aggregation, and was found to be non-toxic."}
{"id": "PMID:224113", "title": "Comparison of activation and blocking procedures in the use of defined antigen substrate spheres (DASS) for quantitative and visual assessment of conjugate activity.", "content": "The use of Sepharose beads in the defined antigen substrate sphere (DASS) immunofluorescent system has been restricted by the need for sophisticated equipment for fluorescence quantitation since reliable subjective reading is not possible. This paper describes a method for visual assessment of results in this system. Antigen is coupled to sodium metaperiodate activated. Cross-linked Sepharose 4B beads and blocked with rhodamine-BSA prior to reduction. This procedure eliminates the use of the hazardous cyanogen bromide activation process and is potentially suitable for use in both direct systems for evaluation of specificity and potency of fluorescent conjugates and in indirect systems for serological screening of sera for specific antibody.", "contents": "Comparison of activation and blocking procedures in the use of defined antigen substrate spheres (DASS) for quantitative and visual assessment of conjugate activity. The use of Sepharose beads in the defined antigen substrate sphere (DASS) immunofluorescent system has been restricted by the need for sophisticated equipment for fluorescence quantitation since reliable subjective reading is not possible. This paper describes a method for visual assessment of results in this system. Antigen is coupled to sodium metaperiodate activated. Cross-linked Sepharose 4B beads and blocked with rhodamine-BSA prior to reduction. This procedure eliminates the use of the hazardous cyanogen bromide activation process and is potentially suitable for use in both direct systems for evaluation of specificity and potency of fluorescent conjugates and in indirect systems for serological screening of sera for specific antibody."}
{"id": "PMID:224114", "title": "Detection of antibodies to Sendai virus by enzyme-linked immunosorbent assay (ELISA).", "content": "An enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies to Sendai virus, a paramyxovirus, is described. The assay was found to be about 20-fold more sensitive than the hemagglutination inhibition assay. Differentiation between virus specific IgG and IgM is possible. The test appears to be especially useful in the study of early events in antibody formation in vivo as well as in vitro.", "contents": "Detection of antibodies to Sendai virus by enzyme-linked immunosorbent assay (ELISA). An enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies to Sendai virus, a paramyxovirus, is described. The assay was found to be about 20-fold more sensitive than the hemagglutination inhibition assay. Differentiation between virus specific IgG and IgM is possible. The test appears to be especially useful in the study of early events in antibody formation in vivo as well as in vitro."}
{"id": "PMID:224115", "title": "Comparative ultrastructure and cytochemistry of epidermal responses to tape stripping, ethanol and vitamin A acid in hairless mice.", "content": "The responses of hairless mouse epidermis to tape stripping, ethanol and vitamin A acid were compared using electron microscopy and cytochemistry. Stripping the skin 4 times with cellophane tape removed most of the stratum corneum and caused the development of enlarged intercellular spaces and dense intramitochondrial inclusions. These changes began within an hour, reached a maximum by 24 hr, and subsided by about 4 days. There was also some accumulation of glycogen and the development of occasional basal lamina breaks and a few intracellular lipid droplets by 24 hr. Topically applied ethanol (95%) produced a similar response, though less damaging. In addition, ethanol induced the formation of numerous lipid droplets in the cytoplasm of keratinocytes by 24 hr and often caused sloughing of the stratum corneum. Vitamin A acid (3%) was dissolved in propylene glycol for application to the skin. We found the application of propylene glycol alone to produce no epidermal changes. Vitamin A acid produced mild damaging effects with small intercellular spaces and intramitochondrial inclusions, but no lipid droplets or glycogen were detected. Vitamin A acid also caused dramatic inhibition of keratinization by 24 hr. Intramitochondrial inclusions were digested by protease, indicating a protein component and they also stained with silver methenamine, indicating the presence of glycogen or glycoprotein.", "contents": "Comparative ultrastructure and cytochemistry of epidermal responses to tape stripping, ethanol and vitamin A acid in hairless mice. The responses of hairless mouse epidermis to tape stripping, ethanol and vitamin A acid were compared using electron microscopy and cytochemistry. Stripping the skin 4 times with cellophane tape removed most of the stratum corneum and caused the development of enlarged intercellular spaces and dense intramitochondrial inclusions. These changes began within an hour, reached a maximum by 24 hr, and subsided by about 4 days. There was also some accumulation of glycogen and the development of occasional basal lamina breaks and a few intracellular lipid droplets by 24 hr. Topically applied ethanol (95%) produced a similar response, though less damaging. In addition, ethanol induced the formation of numerous lipid droplets in the cytoplasm of keratinocytes by 24 hr and often caused sloughing of the stratum corneum. Vitamin A acid (3%) was dissolved in propylene glycol for application to the skin. We found the application of propylene glycol alone to produce no epidermal changes. Vitamin A acid produced mild damaging effects with small intercellular spaces and intramitochondrial inclusions, but no lipid droplets or glycogen were detected. Vitamin A acid also caused dramatic inhibition of keratinization by 24 hr. Intramitochondrial inclusions were digested by protease, indicating a protein component and they also stained with silver methenamine, indicating the presence of glycogen or glycoprotein."}
{"id": "PMID:224120", "title": "The effect of fasting on the adrenergic receptor activity of human adipocytes.", "content": "To assess the influence of fasting of the alpha- and beta-adrenergic receptor activities of human adipocytes, subcutaneous adipose tissue was obtained from normal obese subjects in the fed state and after 3 days of fasting. Isolated cells prepared from the adipose tissue were incubated with epinephrine, 10(-6)M, and in the presence of the alpha-blocker phentolamine, 10(-5)M, and the beta-blocker propranolol, 10(-5)M, respectively; intracellular cyclic AMP levels and glycerol released into the buffer were measured. Consistent with past observations, epinephrine stimulated cyclic AMP and glycerol release when incubated with cells from fed subjects. Phentolamine enhanced this action and propranolol reduced it below the basal level. In contrast, epinephrine suppressed cyclic AMP and lipolysis when incubated with adipocytes from fasted individuals. This reversal in the effect of epinephrine on adipocy.se in alpha-activity. Additional studies suggest that this change in alpha- and beta-adrenergic receptor balance occurred after 1 day of fast and was not significantly exaggerated when fast was prolonged to 8 days. These findings are consistent with the view that in the fasting state the sympathetic nervous system and circulating catecholamines act to conserve adipose tissue triglyceride.", "contents": "The effect of fasting on the adrenergic receptor activity of human adipocytes. To assess the influence of fasting of the alpha- and beta-adrenergic receptor activities of human adipocytes, subcutaneous adipose tissue was obtained from normal obese subjects in the fed state and after 3 days of fasting. Isolated cells prepared from the adipose tissue were incubated with epinephrine, 10(-6)M, and in the presence of the alpha-blocker phentolamine, 10(-5)M, and the beta-blocker propranolol, 10(-5)M, respectively; intracellular cyclic AMP levels and glycerol released into the buffer were measured. Consistent with past observations, epinephrine stimulated cyclic AMP and glycerol release when incubated with cells from fed subjects. Phentolamine enhanced this action and propranolol reduced it below the basal level. In contrast, epinephrine suppressed cyclic AMP and lipolysis when incubated with adipocytes from fasted individuals. This reversal in the effect of epinephrine on adipocy.se in alpha-activity. Additional studies suggest that this change in alpha- and beta-adrenergic receptor balance occurred after 1 day of fast and was not significantly exaggerated when fast was prolonged to 8 days. These findings are consistent with the view that in the fasting state the sympathetic nervous system and circulating catecholamines act to conserve adipose tissue triglyceride."}
{"id": "PMID:224121", "title": "Hemodialysis hypotension is not the result of uremic peripheral autonomic neuropathy.", "content": "Five chronic hemodialysis patients with persistent hypotension during dialysis (MAP: 74.2 +/- 3.1 mm Hg) were given a number of standard tests of autonomic nervous system function and compared with eight normotensive hemodialysis patients (MAP: 96.4 +/- 3.4 mm Hg). Tests of efferent sympathetic nerves were normal in both groups, as were plasma catecholamine levels and the cold pressor test. The response to Valsalva maneuver and the venoconstriction reflex were generally abnormal and did not differentiate between the two groups. When adjusted for age and MAP, the baroreceptor slope to a high-pressure stimulus was diminished only in the hypotensive subjects. This result reinforces the previously described finding that many uremic patients do not develop a normal cardioacceleration during hypotension. Although reduced baroreceptor sensitivity may be a factor in the chronic hypotension of some hemodialysis patients, autonomic dysfunction alone is not a sufficient explanation of this phenomenon.", "contents": "Hemodialysis hypotension is not the result of uremic peripheral autonomic neuropathy. Five chronic hemodialysis patients with persistent hypotension during dialysis (MAP: 74.2 +/- 3.1 mm Hg) were given a number of standard tests of autonomic nervous system function and compared with eight normotensive hemodialysis patients (MAP: 96.4 +/- 3.4 mm Hg). Tests of efferent sympathetic nerves were normal in both groups, as were plasma catecholamine levels and the cold pressor test. The response to Valsalva maneuver and the venoconstriction reflex were generally abnormal and did not differentiate between the two groups. When adjusted for age and MAP, the baroreceptor slope to a high-pressure stimulus was diminished only in the hypotensive subjects. This result reinforces the previously described finding that many uremic patients do not develop a normal cardioacceleration during hypotension. Although reduced baroreceptor sensitivity may be a factor in the chronic hypotension of some hemodialysis patients, autonomic dysfunction alone is not a sufficient explanation of this phenomenon."}
{"id": "PMID:224122", "title": "Chemotactic factor-induced superoxide radical generation by human neutrophils: requirement for proteinase (esterase) activity.", "content": "The requirement for proteinase (esterase) activity in the generation of O2- by human peripheral neutrophils was investigated. Neutrophils were activated by exposure to the chemotactic peptide FMLP and superoxide generation was assessed by ferricytochrome C reduction. Inhibition of O2- generation was observed by pretreating cells with the chloromethyl ketone derivatives of tosyl-phenylalanine (TPCK, ID50 2.2 X 10(-5)M) and tosyl-lysine (TLCK, ID50 1.9 X 10(-4)M). Dose-dependent inhibition was also noted with synthetic proteinase substrates, especially those of chymotrypsin-like specificity, phenylalanine and tryptophan methyl esters (ID50S approximately 1.5 X 10(-4)M), as compared to derivatives of basic amino acids, arginine and acetyl-lysine methyl esters, which caused negligible inhibition at 10(-3M. The inhibition of O2- generation demonstrated by TryME was time- and temperature-dependent and reversible with washing of the cells, whereas the inhibition seen with TPCK was irreversible. DFP at high concentrations, 10(-3)M or greater, caused moderate inhibition of O2- generation that was unaffected by exogenous serine and almost completely reversible by washing the cells. TPCK and TryME, at concentrations that caused marked inhibition of O2- generation, had no effect on the fmlp-induced calcium-45 uptake by the cells. These studies suggest that intact proteinase function is required for O2- generation and that this step follows the calcium influx in the activation sequence induced by FMLP.", "contents": "Chemotactic factor-induced superoxide radical generation by human neutrophils: requirement for proteinase (esterase) activity. The requirement for proteinase (esterase) activity in the generation of O2- by human peripheral neutrophils was investigated. Neutrophils were activated by exposure to the chemotactic peptide FMLP and superoxide generation was assessed by ferricytochrome C reduction. Inhibition of O2- generation was observed by pretreating cells with the chloromethyl ketone derivatives of tosyl-phenylalanine (TPCK, ID50 2.2 X 10(-5)M) and tosyl-lysine (TLCK, ID50 1.9 X 10(-4)M). Dose-dependent inhibition was also noted with synthetic proteinase substrates, especially those of chymotrypsin-like specificity, phenylalanine and tryptophan methyl esters (ID50S approximately 1.5 X 10(-4)M), as compared to derivatives of basic amino acids, arginine and acetyl-lysine methyl esters, which caused negligible inhibition at 10(-3M. The inhibition of O2- generation demonstrated by TryME was time- and temperature-dependent and reversible with washing of the cells, whereas the inhibition seen with TPCK was irreversible. DFP at high concentrations, 10(-3)M or greater, caused moderate inhibition of O2- generation that was unaffected by exogenous serine and almost completely reversible by washing the cells. TPCK and TryME, at concentrations that caused marked inhibition of O2- generation, had no effect on the fmlp-induced calcium-45 uptake by the cells. These studies suggest that intact proteinase function is required for O2- generation and that this step follows the calcium influx in the activation sequence induced by FMLP."}
{"id": "PMID:224123", "title": "Virology studies and Bell's palsy.", "content": "A retrospective analysis of 104 cases of facial nerve paralysis is presented, attention being focused on possible clues to link Bell's palsy with a virus infection. The findings are compared to those of another larger prospective series of cases. Some recent developments which suggest that Bell's palsy represents a reactivation of herpes simplex virus, rather than a primary infection, are discussed.", "contents": "Virology studies and Bell's palsy. A retrospective analysis of 104 cases of facial nerve paralysis is presented, attention being focused on possible clues to link Bell's palsy with a virus infection. The findings are compared to those of another larger prospective series of cases. Some recent developments which suggest that Bell's palsy represents a reactivation of herpes simplex virus, rather than a primary infection, are discussed."}
{"id": "PMID:224124", "title": "Traumatic aneurysm of the internal carotid artery and epistaxis. (Review of literature and report of a case).", "content": "A review of 108 years of world literature revealed 69 cases fulfilling the picture of a clinical syndrome of head injury, a latent period followed by epistaxis and cranial nerve lesions. A similar case has been added which is the fourth case to be reported to be due to a bullet injury. The applied anatomy of the intracranial internal carotid artery (ICA) and the aetiology, clinical syndrome, pathology, diagnosis, prognosis and management of ICA aneurysms have been briefly discussed.", "contents": "Traumatic aneurysm of the internal carotid artery and epistaxis. (Review of literature and report of a case). A review of 108 years of world literature revealed 69 cases fulfilling the picture of a clinical syndrome of head injury, a latent period followed by epistaxis and cranial nerve lesions. A similar case has been added which is the fourth case to be reported to be due to a bullet injury. The applied anatomy of the intracranial internal carotid artery (ICA) and the aetiology, clinical syndrome, pathology, diagnosis, prognosis and management of ICA aneurysms have been briefly discussed."}
{"id": "PMID:224125", "title": "The clinical evaluation of a new clobetasol propionate preparation in the treatment of otitis externa.", "content": "A new preparation containing clobetasol propionate, tetracycline and nystatin was compared with Otosporin in the the treatment of otitis externa. Thirty-two patients with bilateral disease and seventeen with unilateral disease completed the trial. Signs and symptoms were assessed by the clinician initially and at varying times after treatment. Both preparations were effective in relieving the symptoms with the majority of patients noticing improvement within seven days. Clobetasol propionate ear drops were significantly better than Otosporin when assessed on the patient's last visit to the hospital (p less than 0.05). There were less relapses in the clobetasol propionate group than in the Otosporin group.", "contents": "The clinical evaluation of a new clobetasol propionate preparation in the treatment of otitis externa. A new preparation containing clobetasol propionate, tetracycline and nystatin was compared with Otosporin in the the treatment of otitis externa. Thirty-two patients with bilateral disease and seventeen with unilateral disease completed the trial. Signs and symptoms were assessed by the clinician initially and at varying times after treatment. Both preparations were effective in relieving the symptoms with the majority of patients noticing improvement within seven days. Clobetasol propionate ear drops were significantly better than Otosporin when assessed on the patient's last visit to the hospital (p less than 0.05). There were less relapses in the clobetasol propionate group than in the Otosporin group."}
{"id": "PMID:224126", "title": "Temporal oscillations in neuronal nets.", "content": "A model for the interactions of cortical neurons is derived and analyzed. It is shown that small amplitude spatially inhomogeneous standing oscillations can bifurcate from the rest state. In a periodic domain, traveling wave trains exist. Stability of these patterns is discussed in terms of biological parameters. Homoclinic and heteroclinic orbits are demonstrated for the space-clamped system.", "contents": "Temporal oscillations in neuronal nets. A model for the interactions of cortical neurons is derived and analyzed. It is shown that small amplitude spatially inhomogeneous standing oscillations can bifurcate from the rest state. In a periodic domain, traveling wave trains exist. Stability of these patterns is discussed in terms of biological parameters. Homoclinic and heteroclinic orbits are demonstrated for the space-clamped system."}
{"id": "PMID:224127", "title": "Existence and stability of local excitations in homogeneous neural fields.", "content": "Dynamics of excitation patterns is studied in one-dimensional homogeneous lateral-inhibition type neural fields. The existence of a local excitation pattern solution as well as its waveform stability is proved by the use of the Schauder fixed-point theorem and a generalized version of the Perron-Frobenius theorem of positive matrices to the fuction space. The dynamcis of the field is in general multi-stable so that the field can keep short-term memory.", "contents": "Existence and stability of local excitations in homogeneous neural fields. Dynamics of excitation patterns is studied in one-dimensional homogeneous lateral-inhibition type neural fields. The existence of a local excitation pattern solution as well as its waveform stability is proved by the use of the Schauder fixed-point theorem and a generalized version of the Perron-Frobenius theorem of positive matrices to the fuction space. The dynamcis of the field is in general multi-stable so that the field can keep short-term memory."}
{"id": "PMID:224129", "title": "Adrenocorticotrophin-related peptides in adult and foetal sheep pituitary glands.", "content": "Differences in foetal and adult adrenal function may be due to qualitative as well as quantitative changes in the pituitary corticotrophic stimulus. Pituitary glands from adult and foetal sheep were freshly dissected and stored at -70 degrees C until extracted at pH 1.5. The extracts were subjected to chromatography on Sephadex G-100 superfine and fractions were assayed by multiple radioimmunoassays directed against the NH2- and CO2H-terminal sequences of ACTH and lipotrophin (LPH). Peaks corresponding to beta-melanocyte-stimulating hormone (beta-MSH), beta-LHP, gamma-LPH, beta-endorphin and ACTH were identified, with little or no evidence for the presence of alpha-MSH and corticotrophin-like intermediate lobe peptide. Three peaks of large molecular weight material, A. B and C, were identified and their relative proportions shown to be considerably greater in the foetus than in the adult. The immunoassay profile of peaks A and B suggested that they were 'stem hormones' which could give rise to a family of biologically active peptides. Since the 'family tree' which they engender varies according to the stage of development, it is proposed that the changes in the 'trophic family' may explain the different adrenal responses of the foetal and adult sheep.", "contents": "Adrenocorticotrophin-related peptides in adult and foetal sheep pituitary glands. Differences in foetal and adult adrenal function may be due to qualitative as well as quantitative changes in the pituitary corticotrophic stimulus. Pituitary glands from adult and foetal sheep were freshly dissected and stored at -70 degrees C until extracted at pH 1.5. The extracts were subjected to chromatography on Sephadex G-100 superfine and fractions were assayed by multiple radioimmunoassays directed against the NH2- and CO2H-terminal sequences of ACTH and lipotrophin (LPH). Peaks corresponding to beta-melanocyte-stimulating hormone (beta-MSH), beta-LHP, gamma-LPH, beta-endorphin and ACTH were identified, with little or no evidence for the presence of alpha-MSH and corticotrophin-like intermediate lobe peptide. Three peaks of large molecular weight material, A. B and C, were identified and their relative proportions shown to be considerably greater in the foetus than in the adult. The immunoassay profile of peaks A and B suggested that they were 'stem hormones' which could give rise to a family of biologically active peptides. Since the 'family tree' which they engender varies according to the stage of development, it is proposed that the changes in the 'trophic family' may explain the different adrenal responses of the foetal and adult sheep."}
{"id": "PMID:224130", "title": "Priming effect of luteinizing hormone releasing factor in vitro: role of protein synthesis, contractile elements, Ca2+ and cyclic AMP.", "content": "The mechanism of the priming effect of luteinizing hormone releasing factor (LH-RF) upon gonadotrophin secretion was studied using short-term incubation of hemipituitary glands from pro-oestrous rats. The dependence of the priming, but not the LH releasing action of LH-RF on protein synthesis in pituitary tissue was confirmed. Cytochalasin B failed to affect the first response to LH-RF, but abolished the priming effect, suggesting that the integrity of cellular microfilaments was essential. Colchicine and vinblastine did not modify the response to LH-RF. Neither inhibitors of DNA nor the inhibitor of RNA polymerase II, alpha-amanitin, significantly affected the priming action of LH-RF. Normal extracellular concentrations of Ca2+ were necessary for gonadotrophin release, but the priming effect was not significantly affected by low extracellular Ca2+ and could not be elicited by raising intracellular Ca2+ concentrations. Adenosine 3':5'-cyclic phosphate did not appear to act as a second messenger for either the gonadotrophin releasing or the priming action of LH-RF.", "contents": "Priming effect of luteinizing hormone releasing factor in vitro: role of protein synthesis, contractile elements, Ca2+ and cyclic AMP. The mechanism of the priming effect of luteinizing hormone releasing factor (LH-RF) upon gonadotrophin secretion was studied using short-term incubation of hemipituitary glands from pro-oestrous rats. The dependence of the priming, but not the LH releasing action of LH-RF on protein synthesis in pituitary tissue was confirmed. Cytochalasin B failed to affect the first response to LH-RF, but abolished the priming effect, suggesting that the integrity of cellular microfilaments was essential. Colchicine and vinblastine did not modify the response to LH-RF. Neither inhibitors of DNA nor the inhibitor of RNA polymerase II, alpha-amanitin, significantly affected the priming action of LH-RF. Normal extracellular concentrations of Ca2+ were necessary for gonadotrophin release, but the priming effect was not significantly affected by low extracellular Ca2+ and could not be elicited by raising intracellular Ca2+ concentrations. Adenosine 3':5'-cyclic phosphate did not appear to act as a second messenger for either the gonadotrophin releasing or the priming action of LH-RF."}
{"id": "PMID:224131", "title": "Do hypothalamic regulatory factors other than luteinizing hormone releasing factor exert a priming effect?", "content": "Extracts of hypothalamic tissue were applied to pituitary tissue in vitro to see whether they could exert a priming effect on gonadotrophin, adrenocorticotrophin, thyrotrophin or prolactin secretion. A clear-cut priming effect was seen only for gonadotrophin secretion.", "contents": "Do hypothalamic regulatory factors other than luteinizing hormone releasing factor exert a priming effect? Extracts of hypothalamic tissue were applied to pituitary tissue in vitro to see whether they could exert a priming effect on gonadotrophin, adrenocorticotrophin, thyrotrophin or prolactin secretion. A clear-cut priming effect was seen only for gonadotrophin secretion."}
{"id": "PMID:224132", "title": "An extra-adrenal action of adrenocorticotrophin: physiological induction of lipolysis by secretion of adrenocorticotrophin in obese rabbits.", "content": "The effect of minor stressful stimuli (saline infusions or venepunctures) on lipid mobilization (estimated by plasma free fatty acids (FFA) and glycerol levels) was studied in two strains of conscious rabbits of various ages. Infusions of 0.9% (w/v) NaCl solution induced a prompt increase of FFA levels in naturally obese rabbits while this effect was absent in younger lighter animals. Administration of propranolol (a beta-adrenoceptor blocking drug) beforehand did not prevent lipid mobilization. Adipose tissue in vitro was completely unresponsive to the lipid mobilizing action of adrenaline. The initial output of ACTH induced by stressful stimuli was quickly followed by the increase in the plasma concentration of FFA. A highly significant correlation (r = 0.84 or 0.85; P less than 0.01) existed between plasma ACTH and FFA levels 30 and 60 min after the start of stress. Dexamethasone completely prevented lipid mobilization while adipose tissue in vivo and in vitro responded strongly to ACTH. Consequently the lack of response of plasma FFA concentrations in corticosteroid-treated rabbits seemed to be linked to the failure of the pituitary gland to mobilize ACTH rather than to the unresponsiveness of adipose tissue to the pituitary hormone. Our data indicate that in the rabbit, under conditions of stress, ACTH is of greater physiological importance than catecholamines in the control of lipolysis.", "contents": "An extra-adrenal action of adrenocorticotrophin: physiological induction of lipolysis by secretion of adrenocorticotrophin in obese rabbits. The effect of minor stressful stimuli (saline infusions or venepunctures) on lipid mobilization (estimated by plasma free fatty acids (FFA) and glycerol levels) was studied in two strains of conscious rabbits of various ages. Infusions of 0.9% (w/v) NaCl solution induced a prompt increase of FFA levels in naturally obese rabbits while this effect was absent in younger lighter animals. Administration of propranolol (a beta-adrenoceptor blocking drug) beforehand did not prevent lipid mobilization. Adipose tissue in vitro was completely unresponsive to the lipid mobilizing action of adrenaline. The initial output of ACTH induced by stressful stimuli was quickly followed by the increase in the plasma concentration of FFA. A highly significant correlation (r = 0.84 or 0.85; P less than 0.01) existed between plasma ACTH and FFA levels 30 and 60 min after the start of stress. Dexamethasone completely prevented lipid mobilization while adipose tissue in vivo and in vitro responded strongly to ACTH. Consequently the lack of response of plasma FFA concentrations in corticosteroid-treated rabbits seemed to be linked to the failure of the pituitary gland to mobilize ACTH rather than to the unresponsiveness of adipose tissue to the pituitary hormone. Our data indicate that in the rabbit, under conditions of stress, ACTH is of greater physiological importance than catecholamines in the control of lipolysis."}
{"id": "PMID:224133", "title": "Secretion of aldosterone in response to histamine in hypophysectomized-nephrectomized dogs.", "content": "In hypophysectomized-nephrectomized dogs after intravenous injection of histamine, a marked increase was observed in the rate of secretion of aldosterone, although it was smaller than that in intact dogs. Hypophysectomy plus bilateral nephrectomy greatly impaired the secretion of corticosterone and cortisol in the dog in response to histamine. However, a small yet significant increase in corticosterone and cortisol secretion was observed in hypophysectomized-nephrectomized dogs after intravenous injection of histamine. Additional experiments showed that plasma concentrations of potassium and sodium in hypophysectomized-nephrectomized dogs remained unchanged after intravenous injection of histamine. These results suggest that histamine stimulates aldosterone secretion in the dog partly by a direct effect on the adrenal cortical cells, whereas the effect of histamine on corticosterone and cortisol secretion is mediated mainly, but not totally, by pituitary release of ACTH.", "contents": "Secretion of aldosterone in response to histamine in hypophysectomized-nephrectomized dogs. In hypophysectomized-nephrectomized dogs after intravenous injection of histamine, a marked increase was observed in the rate of secretion of aldosterone, although it was smaller than that in intact dogs. Hypophysectomy plus bilateral nephrectomy greatly impaired the secretion of corticosterone and cortisol in the dog in response to histamine. However, a small yet significant increase in corticosterone and cortisol secretion was observed in hypophysectomized-nephrectomized dogs after intravenous injection of histamine. Additional experiments showed that plasma concentrations of potassium and sodium in hypophysectomized-nephrectomized dogs remained unchanged after intravenous injection of histamine. These results suggest that histamine stimulates aldosterone secretion in the dog partly by a direct effect on the adrenal cortical cells, whereas the effect of histamine on corticosterone and cortisol secretion is mediated mainly, but not totally, by pituitary release of ACTH."}
{"id": "PMID:224134", "title": "Anaerobic rat heart: mitochondrial role in calcium uptake and contractility.", "content": "In order to evaluate the manner by which fumarate enhances contractility in the anaerobic heart, we examined Ca++ movements in isolated heart mitochondria and in the isolated perfused heart. Our experiments showed that in isolated antimycin A plus cyanide treated mitochondria: (a) Ca++ uptake was promoted by electron transport generated by fumarate-dependent oxidation of NADH, (b) Ca++ stimulated fumarate-dependent oxidation of NADH, (c) the ratio of Ca++ uptake:NADH oxidized was 1.7 and (d) the Ca++ sequestered is transiently highly mobile and is rapidly released upon collapse of the membrane potential. In anaerobic hearts perfused with glucose plus fumarate, malate and glutamate Ca++ levels were the same as those in oxygenated hearts while in anaerobic organs perfused with or without glucose Ca++ content was appreciably lower. Succinate production in anaerobic heart perfusions was related to: (a) an increased retention of Ca++ by the heart, (b) a diminution in peak aortic pressure generated by cardiac contractions and (c) an increase in heart rate. The information obtained indicates that mitochondria have a capability for Ca++ movement which be used physiologically, particularly in fumarate perfused anaerobic hearts, to assist the mechanism for contraction and relaxation of the heart.", "contents": "Anaerobic rat heart: mitochondrial role in calcium uptake and contractility. In order to evaluate the manner by which fumarate enhances contractility in the anaerobic heart, we examined Ca++ movements in isolated heart mitochondria and in the isolated perfused heart. Our experiments showed that in isolated antimycin A plus cyanide treated mitochondria: (a) Ca++ uptake was promoted by electron transport generated by fumarate-dependent oxidation of NADH, (b) Ca++ stimulated fumarate-dependent oxidation of NADH, (c) the ratio of Ca++ uptake:NADH oxidized was 1.7 and (d) the Ca++ sequestered is transiently highly mobile and is rapidly released upon collapse of the membrane potential. In anaerobic hearts perfused with glucose plus fumarate, malate and glutamate Ca++ levels were the same as those in oxygenated hearts while in anaerobic organs perfused with or without glucose Ca++ content was appreciably lower. Succinate production in anaerobic heart perfusions was related to: (a) an increased retention of Ca++ by the heart, (b) a diminution in peak aortic pressure generated by cardiac contractions and (c) an increase in heart rate. The information obtained indicates that mitochondria have a capability for Ca++ movement which be used physiologically, particularly in fumarate perfused anaerobic hearts, to assist the mechanism for contraction and relaxation of the heart."}
{"id": "PMID:224136", "title": "Hormone-induced pigment translocations in amphibian dermal iridophores, in vitro: changes in cell shape.", "content": "Hormone-induced pigment translocation studies were conducted at both the light and electron microscopic levels on cultured dermal iridophores from the Mexican leaf frog, Pachymedusa dacnicolor. Two distinct types of dermal iridophores were characterized which differed in (1) their in vivo locations, (2) their overall morphologies in vitro, (3) their responses to alpha-MSH, ACTH, c-AMP or theophylline, (4) their physical alterations of light, and (5) certain ultrastructural features. One iridophore (Type I) was found to be physiologically responsive to the above hormones or agents by a reversible retraction of cellular processes and a thickening of the cell body, an event which is inhibited by cytochalasin B. The other iridophore (Type II) appeared to be unresponsive. Type I iridophores contain cube-like pigmentary organelles, refractosomes, while Type II iridophores contain larger, bar-shaped refractosomes. In addition, both iridophore types contain 60  and 100 A microfilaments as well as microtubules. By in large, micorfilaments were found within microvilli, beneath and parallel to the plasma membrane and in the perinuclear region. Occasionally, bundles of 100 A microfilaments were found between layers of refractosomes in Type I iridophores. These results are discussed in relation to hormone-induced changes in cell shape.", "contents": "Hormone-induced pigment translocations in amphibian dermal iridophores, in vitro: changes in cell shape. Hormone-induced pigment translocation studies were conducted at both the light and electron microscopic levels on cultured dermal iridophores from the Mexican leaf frog, Pachymedusa dacnicolor. Two distinct types of dermal iridophores were characterized which differed in (1) their in vivo locations, (2) their overall morphologies in vitro, (3) their responses to alpha-MSH, ACTH, c-AMP or theophylline, (4) their physical alterations of light, and (5) certain ultrastructural features. One iridophore (Type I) was found to be physiologically responsive to the above hormones or agents by a reversible retraction of cellular processes and a thickening of the cell body, an event which is inhibited by cytochalasin B. The other iridophore (Type II) appeared to be unresponsive. Type I iridophores contain cube-like pigmentary organelles, refractosomes, while Type II iridophores contain larger, bar-shaped refractosomes. In addition, both iridophore types contain 60  and 100 A microfilaments as well as microtubules. By in large, micorfilaments were found within microvilli, beneath and parallel to the plasma membrane and in the perinuclear region. Occasionally, bundles of 100 A microfilaments were found between layers of refractosomes in Type I iridophores. These results are discussed in relation to hormone-induced changes in cell shape."}
{"id": "PMID:224137", "title": "The effect of collagen on the cyclic AMP content of embryonic somites.", "content": "Previous studies have demonstrated that collagen substrates stimulate in vitro somite chondrogenesis, and that agents that elevate intracellular cyclic AMP levels in hibit the ability of somites to respond to the inductive influence of collagen. In the present investigation, radiommunoassay was utilized to compare the cyclic AMP content of somite explants cultured on purified Type I collagen substrates with control explants cultured on Millipore filters. During the period of culture, the cyclic AMP content of collagen-treated explants is significantly lower than the cyclic AMP content of control explants. The cyclic AMP content of collagen-treated explants is 66% of control values as early as one hour following the initiation of culture, and the cyclic AMP content of collagen-treated explants remains lower than controls throughout the 3-day cultured period. The greatest difference in the cyclic AMP content of collagen-treated and control explants is observed at the seventeenth hour of culture, at which time the cyclic AMP content of collagen-treated explants is 56% of controls. These results combined with previous studies provides support for the hypothesis that collagen elicits a reduction in the cyclic AMP content of embroyic somites and that this reduction is necessary to trigger chondrogenic differentiation.", "contents": "The effect of collagen on the cyclic AMP content of embryonic somites. Previous studies have demonstrated that collagen substrates stimulate in vitro somite chondrogenesis, and that agents that elevate intracellular cyclic AMP levels in hibit the ability of somites to respond to the inductive influence of collagen. In the present investigation, radiommunoassay was utilized to compare the cyclic AMP content of somite explants cultured on purified Type I collagen substrates with control explants cultured on Millipore filters. During the period of culture, the cyclic AMP content of collagen-treated explants is significantly lower than the cyclic AMP content of control explants. The cyclic AMP content of collagen-treated explants is 66% of control values as early as one hour following the initiation of culture, and the cyclic AMP content of collagen-treated explants remains lower than controls throughout the 3-day cultured period. The greatest difference in the cyclic AMP content of collagen-treated and control explants is observed at the seventeenth hour of culture, at which time the cyclic AMP content of collagen-treated explants is 56% of controls. These results combined with previous studies provides support for the hypothesis that collagen elicits a reduction in the cyclic AMP content of embroyic somites and that this reduction is necessary to trigger chondrogenic differentiation."}
{"id": "PMID:224138", "title": "Dopamine blockade of the thyroliberin -- induced cyclic AMP accumulation in rat anterior pituitary.", "content": "Effects of dopamine and thyroliberin on the cyclic AMP concentration in the rat anterior pituitary gland were investigated in vitro. Dopamine by itself had no effect on the anterior pituitary cAMP concentration but inhibited the cAMP-accumulating effect of thyroliberin.", "contents": "Dopamine blockade of the thyroliberin -- induced cyclic AMP accumulation in rat anterior pituitary. Effects of dopamine and thyroliberin on the cyclic AMP concentration in the rat anterior pituitary gland were investigated in vitro. Dopamine by itself had no effect on the anterior pituitary cAMP concentration but inhibited the cAMP-accumulating effect of thyroliberin."}
{"id": "PMID:224139", "title": "Qualitative aspects on motility changes in mice induced by low doses of apomorphine and clonidine.", "content": "Single mice were treated with apomorphine (0.05, 0.2 or 0.8 mg/kg) or clonidine (0.025 or 0.05 mg/kg), and were placed in a new kind of motility meter, allowing classification of movements in terms of size, and also charting the motility with the help of an X/Y pen recorder. All treatments induced reduction of motility in this model. Apomorphine, 0.8 mg/kg, considerably changed the motility type, whereas the lower doses did not. This finding is consistent with earlier studies on gross lobomotor activity and suggests that the higher dose alone evokes a significant direct net stimulation of postsynaptic dopamine receptors, whereas the lower doses merely reduce the physiological stimulation of these receptors by inhibiting dopamine neurotransmission. Clonidine, 0.025 mg/kg, depressed motility at least as much as did 0.05 mg/kg, in agreement with previous behavioural studies.", "contents": "Qualitative aspects on motility changes in mice induced by low doses of apomorphine and clonidine. Single mice were treated with apomorphine (0.05, 0.2 or 0.8 mg/kg) or clonidine (0.025 or 0.05 mg/kg), and were placed in a new kind of motility meter, allowing classification of movements in terms of size, and also charting the motility with the help of an X/Y pen recorder. All treatments induced reduction of motility in this model. Apomorphine, 0.8 mg/kg, considerably changed the motility type, whereas the lower doses did not. This finding is consistent with earlier studies on gross lobomotor activity and suggests that the higher dose alone evokes a significant direct net stimulation of postsynaptic dopamine receptors, whereas the lower doses merely reduce the physiological stimulation of these receptors by inhibiting dopamine neurotransmission. Clonidine, 0.025 mg/kg, depressed motility at least as much as did 0.05 mg/kg, in agreement with previous behavioural studies."}
{"id": "PMID:224140", "title": "The effects of the combined administration of gamma-hydroxybutyrate and diazepam on sleep parameters in the rat.", "content": "The actions of diazepam and gamma-hydroxybutyrate (GHB) were assessed on the sleep-wakefulness cycle of male Wistar rats. One and 2 mg/kg diazepam and 12.5 mg/kg GHB had no effects on the sleep variables. After 25 mg/kg GHB, slow wave sleep (SWS2) was significantly increased. Following the combined administration of non-effective doses of GHB and diazepam, significantly higher amounts of SWS2 at the expense of wakefulness were obtained. The injection of a subconvulsant dose of bicuculline (2.5 mg/kg) prior to treatments which significantly increased SWS2 prevented this effect to show up. It is suggested that the actions of GHB and diazepam on the sleep-awake cycle are related to the same neurotransmitter system.", "contents": "The effects of the combined administration of gamma-hydroxybutyrate and diazepam on sleep parameters in the rat. The actions of diazepam and gamma-hydroxybutyrate (GHB) were assessed on the sleep-wakefulness cycle of male Wistar rats. One and 2 mg/kg diazepam and 12.5 mg/kg GHB had no effects on the sleep variables. After 25 mg/kg GHB, slow wave sleep (SWS2) was significantly increased. Following the combined administration of non-effective doses of GHB and diazepam, significantly higher amounts of SWS2 at the expense of wakefulness were obtained. The injection of a subconvulsant dose of bicuculline (2.5 mg/kg) prior to treatments which significantly increased SWS2 prevented this effect to show up. It is suggested that the actions of GHB and diazepam on the sleep-awake cycle are related to the same neurotransmitter system."}
{"id": "PMID:224141", "title": "Arginine vasotocin as a pineal hormone.", "content": "The pineal nonapeptide hormone arginine vasotocin (AVT) is synthesized by the ependymal cells of the pineal recess and subcommissural organ and stored in so far undefined cells of the pineal gland proper. AVT is first released into the cerebrospinal fluid (CSF) and reaches the blood only secondarily after its absorption from CSF. It displays a diurnal rhythm in the pineal and CSF, suggesting its release into the CSF during the night in the dark. Melatonin represents its releasing hormone. AVT exerts both its endocrine and non-endocrine effects by a unique mechanism involving the activation of serotonin neurotransmission in the brain with resultant inhibition of release of hypothalamic releasing and inhibiting hormones and induction of sleep. It produces both its endocrine effects and sleep at concentrations equivalent to only several hundreds of molecules, being thus by far the most active hormone so far known. Midbrain raphe nuclei or some structures intimately correlated with these cell bodies, most contain the extremely sensitive and specific AVT receptors in the mammalian brain. In contrast with its natural analogues arginine vasopressin and oxytocin which are mainly blood hormones, AVT is a CSF hormone whose major if not the sole site of action is the brain itself.", "contents": "Arginine vasotocin as a pineal hormone. The pineal nonapeptide hormone arginine vasotocin (AVT) is synthesized by the ependymal cells of the pineal recess and subcommissural organ and stored in so far undefined cells of the pineal gland proper. AVT is first released into the cerebrospinal fluid (CSF) and reaches the blood only secondarily after its absorption from CSF. It displays a diurnal rhythm in the pineal and CSF, suggesting its release into the CSF during the night in the dark. Melatonin represents its releasing hormone. AVT exerts both its endocrine and non-endocrine effects by a unique mechanism involving the activation of serotonin neurotransmission in the brain with resultant inhibition of release of hypothalamic releasing and inhibiting hormones and induction of sleep. It produces both its endocrine effects and sleep at concentrations equivalent to only several hundreds of molecules, being thus by far the most active hormone so far known. Midbrain raphe nuclei or some structures intimately correlated with these cell bodies, most contain the extremely sensitive and specific AVT receptors in the mammalian brain. In contrast with its natural analogues arginine vasopressin and oxytocin which are mainly blood hormones, AVT is a CSF hormone whose major if not the sole site of action is the brain itself."}
{"id": "PMID:224142", "title": "Sensitivity and cyclic nucleotides in the rat pineal gland.", "content": "beta-Adrenergic stimulation induces serotonin N-acetyltransferase (SNAT) activity in the rat pineal gland. The magnitude and some of the characteristics of this response vary as a function of the gland's previous exposure to stimulation. A period of stimulation results in a subsensitive response to subsequent stimulation. A period without stimulation provides a supersensitive response to subsequent stimulation. Investigations concerned with the mechanisms regulating the rat pineal's sensitivity to beta-adrenergic stimulation are described. These have focused on the regulation of cyclic AMP metabolism. Several of the components involved in the induction of SNAT activity appear to participate in the regulation of sensitivity. These include the beta-adrenergic binding sites, the catecholamine-sensitive adenylate cyclase, the cyclic nucleotide phosphodiesterase, and the cyclic AMP-dependent protein kinase. Thus, the rat pineal's sensitivity to beta-adrenergic stimulation appears to be regulated at multiple sites. Other investigations have focused on the regulation of pineal cyclic GMP metabolism. Unlike cyclic AMP, the stimulation of cyclic GMP synthesis requires the presence of intact nerve endings and of extracellular calcium. Some of the characteristics of pineal cyclic GMP regulation are described.", "contents": "Sensitivity and cyclic nucleotides in the rat pineal gland. beta-Adrenergic stimulation induces serotonin N-acetyltransferase (SNAT) activity in the rat pineal gland. The magnitude and some of the characteristics of this response vary as a function of the gland's previous exposure to stimulation. A period of stimulation results in a subsensitive response to subsequent stimulation. A period without stimulation provides a supersensitive response to subsequent stimulation. Investigations concerned with the mechanisms regulating the rat pineal's sensitivity to beta-adrenergic stimulation are described. These have focused on the regulation of cyclic AMP metabolism. Several of the components involved in the induction of SNAT activity appear to participate in the regulation of sensitivity. These include the beta-adrenergic binding sites, the catecholamine-sensitive adenylate cyclase, the cyclic nucleotide phosphodiesterase, and the cyclic AMP-dependent protein kinase. Thus, the rat pineal's sensitivity to beta-adrenergic stimulation appears to be regulated at multiple sites. Other investigations have focused on the regulation of pineal cyclic GMP metabolism. Unlike cyclic AMP, the stimulation of cyclic GMP synthesis requires the presence of intact nerve endings and of extracellular calcium. Some of the characteristics of pineal cyclic GMP regulation are described."}
{"id": "PMID:224143", "title": "Developmental plasticity of central noradrenaline neurons after neonatal damage--changes in transmitter functions.", "content": "The effects of neonatal 6-hydroxydopamine (6-OH-DA) treatment (systemic administration) on noradrenaline (NA) metabolism, turn over, and receptor characteristics have been investigated in rat brain in the adult stage. This treatment is known to preferentially affect the locus coeruleus (LC) NA system leading to a marked NA denervation in the central cortex and hyperinnervation of NA nerve terminals in the pons and medulla oblongata without influencing the LC perikarya. The main NA metabolite, 3-methoxy-4-hydroxy-phenylglycol (MOPEG) was reduced by about 70% in the cerebral cortex after 6-OH-DA treatment at birth while the endogenous NA was almost completely depleted (-92%). The MOPEG levels were not significantly changed in the pons medulla after 6-OH-DA treatment in contrast to the 60% increase of the endogenous NA concentration. The relative reduction of NA in the cerebral cortex of 6-OH-DA treated rats increased in the cerebral cortex following administration of the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine (H44/68) compared to the control, while the H44/68 induced depletion of NA was reduced in the pons medulla after 6-OH-DA. The steady-state level of endogenous NA and the effect of H44/68 were unchanged in the LC perikarya after 6-OH-DA treatment. These results indicate that the NA turn over in remaining NA nerve terminals in the cerebral cortex is increased after 6-OH-DA, while decreased in the pons-medulla, possible related to changes in the activation of presynaptic alpha-adrenoreceptors in both regions. NA-induced formation of cAMP in vitro was found to be markedly increased in the cerebral cortex after 6-OH-DA, whereas no consistent change was observed in the pons medulla. Measurements of alpha- and beta-receptor binding in vitro using radioligand techniques showed an increase of binding sites (20%--50%) for both receptors in the neocortex aster 6-OH-DA, whereas no changes were observed in the pons medulla. The 6-OH-DA induced changes in NA turnover, cAMP generating systems, and receptor density may all represent compensatory processes following the altered development of the NA neurons induced by 6-OH-DA.", "contents": "Developmental plasticity of central noradrenaline neurons after neonatal damage--changes in transmitter functions. The effects of neonatal 6-hydroxydopamine (6-OH-DA) treatment (systemic administration) on noradrenaline (NA) metabolism, turn over, and receptor characteristics have been investigated in rat brain in the adult stage. This treatment is known to preferentially affect the locus coeruleus (LC) NA system leading to a marked NA denervation in the central cortex and hyperinnervation of NA nerve terminals in the pons and medulla oblongata without influencing the LC perikarya. The main NA metabolite, 3-methoxy-4-hydroxy-phenylglycol (MOPEG) was reduced by about 70% in the cerebral cortex after 6-OH-DA treatment at birth while the endogenous NA was almost completely depleted (-92%). The MOPEG levels were not significantly changed in the pons medulla after 6-OH-DA treatment in contrast to the 60% increase of the endogenous NA concentration. The relative reduction of NA in the cerebral cortex of 6-OH-DA treated rats increased in the cerebral cortex following administration of the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine (H44/68) compared to the control, while the H44/68 induced depletion of NA was reduced in the pons medulla after 6-OH-DA. The steady-state level of endogenous NA and the effect of H44/68 were unchanged in the LC perikarya after 6-OH-DA treatment. These results indicate that the NA turn over in remaining NA nerve terminals in the cerebral cortex is increased after 6-OH-DA, while decreased in the pons-medulla, possible related to changes in the activation of presynaptic alpha-adrenoreceptors in both regions. NA-induced formation of cAMP in vitro was found to be markedly increased in the cerebral cortex after 6-OH-DA, whereas no consistent change was observed in the pons medulla. Measurements of alpha- and beta-receptor binding in vitro using radioligand techniques showed an increase of binding sites (20%--50%) for both receptors in the neocortex aster 6-OH-DA, whereas no changes were observed in the pons medulla. The 6-OH-DA induced changes in NA turnover, cAMP generating systems, and receptor density may all represent compensatory processes following the altered development of the NA neurons induced by 6-OH-DA."}
{"id": "PMID:224148", "title": "Peripheral neuropathy in angioimmunoblastic lymphadenopathy with dysproteinaemia.", "content": "A case of angioimmunoblastic lymphadenopathy with dysproteinaemia complicated by a subacute peripheral neuropathy is described. Clinically  the neuropathy was mainly motor, but pain and paraesthesiae in the legs were also present. Sural nerve biopsy indicated decreased numbers of myelinated fibres, mainly the largest, without actual signs of degeneration or regeneration. However, the occurrence of denervation bands indicated that degeneration had led to loss of myelinated fibres.", "contents": "Peripheral neuropathy in angioimmunoblastic lymphadenopathy with dysproteinaemia. A case of angioimmunoblastic lymphadenopathy with dysproteinaemia complicated by a subacute peripheral neuropathy is described. Clinically  the neuropathy was mainly motor, but pain and paraesthesiae in the legs were also present. Sural nerve biopsy indicated decreased numbers of myelinated fibres, mainly the largest, without actual signs of degeneration or regeneration. However, the occurrence of denervation bands indicated that degeneration had led to loss of myelinated fibres."}
{"id": "PMID:224149", "title": "Ataxia-telangiectasia. Report of a case with Lewy bodies and vascular abnormalities within cerebral tissue.", "content": "The neuropathologic findings in a 31 year old patient with ataxia-telangiectasia are presented. There was an unusually severe and widespread distribution of the recognized abnormalities within the nervous system. In addition, there were Lewy bodies in the substantia nigra and widely distributed vascular changes in cerebral tissue. The nature of the vascular changes is discussed. These findings underline and expand the known spectrum of nervous system involvement in this condition.", "contents": "Ataxia-telangiectasia. Report of a case with Lewy bodies and vascular abnormalities within cerebral tissue. The neuropathologic findings in a 31 year old patient with ataxia-telangiectasia are presented. There was an unusually severe and widespread distribution of the recognized abnormalities within the nervous system. In addition, there were Lewy bodies in the substantia nigra and widely distributed vascular changes in cerebral tissue. The nature of the vascular changes is discussed. These findings underline and expand the known spectrum of nervous system involvement in this condition."}
{"id": "PMID:224150", "title": "Ultrastructural study of zinc pyridinethione-induced peripheral neuropathy.", "content": "This study describes, for the first time, the neuropathy of zinc pyridinethione (ZPT) toxicity in rats. Although hind-limb weakness has been previously reported as a consequence of dietary ZPT ingestion in rats and rabbits, the cause of the paralysis has been unexplained. Sequential morphologic studies in rats fed a diet containing 166 ppm of ZPT revealed a dying-back neuropathy characterized by the early accumulation of tubulo-vesicular profiles in the motor nerve terminals. Continued exposure resulted in similar abnormalities in the intrasmuscular nerves and later in the peroneal and posterior tibial nerves and nerve branches to individual muscles. Axonal degeneration and regeneration followed the initial pathologic changes. There was relative sparing of the sensory nerve terminals of the muscle spindles. Central nervous system axons in the long descending tracts of the spinal cord and in the cerebellar vermis showed similar but quantitatively fewer axonal changes compared to the peripheral nerves. The central effects occurred only after prolonged administration of ZPT.", "contents": "Ultrastructural study of zinc pyridinethione-induced peripheral neuropathy. This study describes, for the first time, the neuropathy of zinc pyridinethione (ZPT) toxicity in rats. Although hind-limb weakness has been previously reported as a consequence of dietary ZPT ingestion in rats and rabbits, the cause of the paralysis has been unexplained. Sequential morphologic studies in rats fed a diet containing 166 ppm of ZPT revealed a dying-back neuropathy characterized by the early accumulation of tubulo-vesicular profiles in the motor nerve terminals. Continued exposure resulted in similar abnormalities in the intrasmuscular nerves and later in the peroneal and posterior tibial nerves and nerve branches to individual muscles. Axonal degeneration and regeneration followed the initial pathologic changes. There was relative sparing of the sensory nerve terminals of the muscle spindles. Central nervous system axons in the long descending tracts of the spinal cord and in the cerebellar vermis showed similar but quantitatively fewer axonal changes compared to the peripheral nerves. The central effects occurred only after prolonged administration of ZPT."}
{"id": "PMID:224151", "title": "Cytologic observations on axotomized feline Betz cells. II. Quantitative ultrastructural findings.", "content": "Quantitative electron microscopic examination was made of Betz cells of two unoperated cats as well as cats subjected to left lateral funiculotomy 5, 10, 28 and 49 days before sacrifice. The percent cytoplasmic composition of chromatolyzed, right-sided Betz cells contributed by cisternal elements of RER, Golgi apparatus and dense bodies and the percent perikaryal membrane apposed by subsurface cisterns were unchanged from the normal despite marked qualitative alterations of the cytoplasm. However, 49 days postoperatively mitochondrial numerical density of axotomized, right-sided Betz cells was significantly less than at 0, 10 and 28 days post funiculotomy. Importantly, normal-appearing Betz cells ipsilateral to corticospinal tract section showed an increase in mitochondrial numerical density 5 days postoperatively. Operation did not induce change in the % perikaryal coverage by axosomatic boutons. Retraction of axosomatic boutons, though often reported for other neuronal populations undergoing axon reaction, is not a necessary feature of the axon reaction of feline Betz cells.", "contents": "Cytologic observations on axotomized feline Betz cells. II. Quantitative ultrastructural findings. Quantitative electron microscopic examination was made of Betz cells of two unoperated cats as well as cats subjected to left lateral funiculotomy 5, 10, 28 and 49 days before sacrifice. The percent cytoplasmic composition of chromatolyzed, right-sided Betz cells contributed by cisternal elements of RER, Golgi apparatus and dense bodies and the percent perikaryal membrane apposed by subsurface cisterns were unchanged from the normal despite marked qualitative alterations of the cytoplasm. However, 49 days postoperatively mitochondrial numerical density of axotomized, right-sided Betz cells was significantly less than at 0, 10 and 28 days post funiculotomy. Importantly, normal-appearing Betz cells ipsilateral to corticospinal tract section showed an increase in mitochondrial numerical density 5 days postoperatively. Operation did not induce change in the % perikaryal coverage by axosomatic boutons. Retraction of axosomatic boutons, though often reported for other neuronal populations undergoing axon reaction, is not a necessary feature of the axon reaction of feline Betz cells."}
{"id": "PMID:224152", "title": "Experimental interfascicular nerve grafting.", "content": "Twenty-nine adult rhesus monkeys underwent complete laceration of both tibial nerves at mid-thigh level and repair by different methods to study the relative efficacy of autogenous interfascicular nerve grafts. Sixteen animals in Group I had an interfascicular graft repair using short sural nerve autografts on one limb and fascicular repair without grafts on the other limb. Thirteen animals in Group II, after having a 1-cm segment of tibial nerve resected, had an interfascicular graft repair without tension in one limb and an epineurial repair under moderate tension in the other limb. Evoked nerve and muscle action potentials and muscle strenght in response to repetitive and tetanic stimulation were recorded as baseline values prelaceration and then on re-exploration at 4, 6, 9, or 12 months. All nerves were examined by light and electron microscopy. Electrophysiological data, particularly muscle strength response, showed non-graft repairs to be superior at 4 and 6 months of regeneration. However, by 9 and 12 months the graft repairs had caught up and were equal to the non-graft repairs. Histologically, it was observed that many axons missed the graft segments and were present in extrafascicular connective tissues. Nonetheless, enough axons regenerated to the distal nerve to explain the success of these relatively short grafts. From the results of these experiments, it is concluded that use of autogenous interfascicular grafts offers no advantage over end-to-end non-graft repair. When and end-to-end repair cannot be achieved, use of short interfascicular nerve grafts is feasible and will work.", "contents": "Experimental interfascicular nerve grafting. Twenty-nine adult rhesus monkeys underwent complete laceration of both tibial nerves at mid-thigh level and repair by different methods to study the relative efficacy of autogenous interfascicular nerve grafts. Sixteen animals in Group I had an interfascicular graft repair using short sural nerve autografts on one limb and fascicular repair without grafts on the other limb. Thirteen animals in Group II, after having a 1-cm segment of tibial nerve resected, had an interfascicular graft repair without tension in one limb and an epineurial repair under moderate tension in the other limb. Evoked nerve and muscle action potentials and muscle strenght in response to repetitive and tetanic stimulation were recorded as baseline values prelaceration and then on re-exploration at 4, 6, 9, or 12 months. All nerves were examined by light and electron microscopy. Electrophysiological data, particularly muscle strength response, showed non-graft repairs to be superior at 4 and 6 months of regeneration. However, by 9 and 12 months the graft repairs had caught up and were equal to the non-graft repairs. Histologically, it was observed that many axons missed the graft segments and were present in extrafascicular connective tissues. Nonetheless, enough axons regenerated to the distal nerve to explain the success of these relatively short grafts. From the results of these experiments, it is concluded that use of autogenous interfascicular grafts offers no advantage over end-to-end non-graft repair. When and end-to-end repair cannot be achieved, use of short interfascicular nerve grafts is feasible and will work."}
{"id": "PMID:224153", "title": "Histological studies of experimental interfascicular graft repairs.", "content": "Biopsies of sutured and grafted primate peripheral nerves were examined by light and electron microscopy after the final set of electrical measurements had been recorded. Inspection of all proximal stumps showed the expected regenerative activity which was not affected by the nature of the nerve repair. Transverse sections through the epineurial, interfascicular, and graft suture lines showed a similar pattern in all animals and at this site nerves sutured by epineurial technique could only be distinguished from those sutured by fascicular technique by loci of the non-absorbable suture. Fascicular repairs, whether done fascicle-to-fascicle or with interposition of grafts, had a more lengthy neuroma than did the epineurial repairs. Maintenance of fascicular architecture through the course of the grafts was variable. Fascicular structure was frequently absent in the central graft segments and in segments close to the second suture site. The method of repair used more proximally could not be distinguished by evaluation of distal stump segments. Measurements of myelinated fiber size made of distal stump axons revealed no statistical difference between the methods of repair.", "contents": "Histological studies of experimental interfascicular graft repairs. Biopsies of sutured and grafted primate peripheral nerves were examined by light and electron microscopy after the final set of electrical measurements had been recorded. Inspection of all proximal stumps showed the expected regenerative activity which was not affected by the nature of the nerve repair. Transverse sections through the epineurial, interfascicular, and graft suture lines showed a similar pattern in all animals and at this site nerves sutured by epineurial technique could only be distinguished from those sutured by fascicular technique by loci of the non-absorbable suture. Fascicular repairs, whether done fascicle-to-fascicle or with interposition of grafts, had a more lengthy neuroma than did the epineurial repairs. Maintenance of fascicular architecture through the course of the grafts was variable. Fascicular structure was frequently absent in the central graft segments and in segments close to the second suture site. The method of repair used more proximally could not be distinguished by evaluation of distal stump segments. Measurements of myelinated fiber size made of distal stump axons revealed no statistical difference between the methods of repair."}
{"id": "PMID:224154", "title": "Atypical fibrous histiocytoma of the thoracic spine. Case report.", "content": "A 14-year-old boy presented with mid-thoracic pain, leg weakness, and bladder dysfunction. Plain x-ray films and bone scan were normal whereas myelography demonstrated an extradural mass extending from T-2 to T-5. Exploration revealed a large tumor adherent to dura and bone. Pathological verification of an atypical fibrous histiocytoma prompted the report of this rare tumor of the vertebral column.", "contents": "Atypical fibrous histiocytoma of the thoracic spine. Case report. A 14-year-old boy presented with mid-thoracic pain, leg weakness, and bladder dysfunction. Plain x-ray films and bone scan were normal whereas myelography demonstrated an extradural mass extending from T-2 to T-5. Exploration revealed a large tumor adherent to dura and bone. Pathological verification of an atypical fibrous histiocytoma prompted the report of this rare tumor of the vertebral column."}
{"id": "PMID:224155", "title": "Longitudinal study of tolyl-reactive IgE antibodies in workers hypersensitive to TDI.", "content": "Three workers with TDI hypersensitivity were evaluated for IgE antibodies to TDI over a period of 13 months. A radioallergosorbent test (RAST) system was employed using p-toly(mono)isocyanate-human serum albumin antigen covalently bound to cyanogen bromide-activated paper discs. IgE antibody titers were consistently elevated in two individuals who experienced several bronchial hypersensitivity responses to TDI during the study period. The responses were either solely asthmatic or asthmatic accompanied by cutaneous hypersensitivity reactions. By contrast, antibody titers in a third subject who had not experienced any hyersensitivity reactions during the study period continually decreased, falling to insignificant levels after 12 months. In the absence of renewed TDI exposure, sensitive workers may have titers indistinguishable from those of workers exposed to TDI but without sensitivity to the chemical.", "contents": "Longitudinal study of tolyl-reactive IgE antibodies in workers hypersensitive to TDI. Three workers with TDI hypersensitivity were evaluated for IgE antibodies to TDI over a period of 13 months. A radioallergosorbent test (RAST) system was employed using p-toly(mono)isocyanate-human serum albumin antigen covalently bound to cyanogen bromide-activated paper discs. IgE antibody titers were consistently elevated in two individuals who experienced several bronchial hypersensitivity responses to TDI during the study period. The responses were either solely asthmatic or asthmatic accompanied by cutaneous hypersensitivity reactions. By contrast, antibody titers in a third subject who had not experienced any hyersensitivity reactions during the study period continually decreased, falling to insignificant levels after 12 months. In the absence of renewed TDI exposure, sensitive workers may have titers indistinguishable from those of workers exposed to TDI but without sensitivity to the chemical."}
{"id": "PMID:224156", "title": "Effects of chronic amorphous silica exposure on sequential pulmonary function.", "content": "To assess clincial effects of precipitated amorphous silica (PAS), the authors reviewed serial spirograms, respiratory questionnaires, and chest radiographs of 165 workers exposed for a mean of 8.6 years. Monthly exposure was graded on a 1 to 4 scale and a \"cumulative exposure index\" (CEI) calculated for each worker from the sum of measured exposure. A \"mean exposure index\" (MEI) was calculated by dividing the CEI by total months exposed. Sputum production and dyspnea were inversely correlated with CEI, while cough and dyspnea correlated with mean pack-years of smoking but not PAS exposure. Linear regression analysis of yearly change of all pulmonary function variables (FVC, FEV1, FEV1/FVC, FEF25-75) showed no correlation with either the dose of PAS (CEI) or total years of exposure. Among 44 workers with a mean exposure time of 18 years (range 10-35 years), yearly decline of FVC and FEV1 were similar to the overall group. Of 143 workers with serial radiographs and exposure to only PAS, none had radiographic pneumoconiosis. Respiratory symptoms in PAS workers correlate with smoking but not with PAS exposure, while serial pulmonary function values and chest radiographs are not adversely affected by long-term exposure.", "contents": "Effects of chronic amorphous silica exposure on sequential pulmonary function. To assess clincial effects of precipitated amorphous silica (PAS), the authors reviewed serial spirograms, respiratory questionnaires, and chest radiographs of 165 workers exposed for a mean of 8.6 years. Monthly exposure was graded on a 1 to 4 scale and a \"cumulative exposure index\" (CEI) calculated for each worker from the sum of measured exposure. A \"mean exposure index\" (MEI) was calculated by dividing the CEI by total months exposed. Sputum production and dyspnea were inversely correlated with CEI, while cough and dyspnea correlated with mean pack-years of smoking but not PAS exposure. Linear regression analysis of yearly change of all pulmonary function variables (FVC, FEV1, FEV1/FVC, FEF25-75) showed no correlation with either the dose of PAS (CEI) or total years of exposure. Among 44 workers with a mean exposure time of 18 years (range 10-35 years), yearly decline of FVC and FEV1 were similar to the overall group. Of 143 workers with serial radiographs and exposure to only PAS, none had radiographic pneumoconiosis. Respiratory symptoms in PAS workers correlate with smoking but not with PAS exposure, while serial pulmonary function values and chest radiographs are not adversely affected by long-term exposure."}
{"id": "PMID:224157", "title": "Cadmium nephropathy--a clinical evaluation.", "content": "Decreased GFR and TmG and increased beta-2-microglobulin excretion were found in a worker with a nine-year exposure to cadmium. The patient's recent marked weight loss and other multiple symptoms could not be explained on these abnormalities or by results of other specialized studies. Increased urinary beta-2-microglobulin without proteinuria but with elevated blood and urine cadmium levels in this patient raises questions about which biological indicators will prove to be most helpful in effectively monitoring cadmium workers.", "contents": "Cadmium nephropathy--a clinical evaluation. Decreased GFR and TmG and increased beta-2-microglobulin excretion were found in a worker with a nine-year exposure to cadmium. The patient's recent marked weight loss and other multiple symptoms could not be explained on these abnormalities or by results of other specialized studies. Increased urinary beta-2-microglobulin without proteinuria but with elevated blood and urine cadmium levels in this patient raises questions about which biological indicators will prove to be most helpful in effectively monitoring cadmium workers."}
{"id": "PMID:224159", "title": "Extrapulmonary manifestations of adenovirus type 7 pneumonia simulating Reye syndrome and the possible role of an adenovirus toxin.", "content": "Three children developed extensive extrapulmonary disease in the course of fatal adenovirus type 7 pneumonia. Several clinical features, including the unexpected onset of coma, suggested the development of Reye syndrome, but biochemical and histopathologic findings were inconsistent with this diagnosis. Virologic and pathologic studies did not reveal evidence of extrapulmonary adenovirus infection, despite clinical involvement of the liver, skeletal muscle, and central nervous system. The detection in premortem sera from all three patients of adenovirus penton antigen, known to be cytotoxic in vitro, suggests a possible mechanism for the production of extrapulmonary pathology in the absence of extrapulmonary virus infection.", "contents": "Extrapulmonary manifestations of adenovirus type 7 pneumonia simulating Reye syndrome and the possible role of an adenovirus toxin. Three children developed extensive extrapulmonary disease in the course of fatal adenovirus type 7 pneumonia. Several clinical features, including the unexpected onset of coma, suggested the development of Reye syndrome, but biochemical and histopathologic findings were inconsistent with this diagnosis. Virologic and pathologic studies did not reveal evidence of extrapulmonary adenovirus infection, despite clinical involvement of the liver, skeletal muscle, and central nervous system. The detection in premortem sera from all three patients of adenovirus penton antigen, known to be cytotoxic in vitro, suggests a possible mechanism for the production of extrapulmonary pathology in the absence of extrapulmonary virus infection."}
{"id": "PMID:224161", "title": "Cytomegaloviruria in older infants in intensive care nurseries.", "content": "Over a four-month period, urine specimens for viral isolation were obtained weekly from all infants older than three weeks in two intensive care nurseries. These babies comprised 43% of the patients in the nurseries surveyed. Cytomegalovirus was cultured from 13 of 93 (14%) of these infants. Eleven of 13 infants who developed cytomegaloviruria were born prematurely, and nine of these 11 were found to be excreting CMV before they reached 40 weeks postconception. Infants excreting CMV received blood transfusions from a mean of 10.45 (+/- 1.80 SE) different donors versus 5.10 (+/- 0.55 SE) for infants without viruria (P less than 0.002) and five of 14 infants undergoing one or more exchange transfusions developed cytomegaloviruria (P less than 0.05). The possible role of other CMV reservoirs and the importance of these findings are discussed.", "contents": "Cytomegaloviruria in older infants in intensive care nurseries. Over a four-month period, urine specimens for viral isolation were obtained weekly from all infants older than three weeks in two intensive care nurseries. These babies comprised 43% of the patients in the nurseries surveyed. Cytomegalovirus was cultured from 13 of 93 (14%) of these infants. Eleven of 13 infants who developed cytomegaloviruria were born prematurely, and nine of these 11 were found to be excreting CMV before they reached 40 weeks postconception. Infants excreting CMV received blood transfusions from a mean of 10.45 (+/- 1.80 SE) different donors versus 5.10 (+/- 0.55 SE) for infants without viruria (P less than 0.002) and five of 14 infants undergoing one or more exchange transfusions developed cytomegaloviruria (P less than 0.05). The possible role of other CMV reservoirs and the importance of these findings are discussed."}
{"id": "PMID:224166", "title": "The actions of excitatory amino acids on motoneurones in the feline spinal cord.", "content": "1. Combined recording or ionophoretic electrodes of the concentric type were used to investigate the depolarizing responses of DL-homocysteate (DLH) and L-glutamate in cat lumbar motoneurones. 2. Typically, DLH responses were slow both in onset and recovery, while glutamate responses were fast in onset and recovery and were frequently accompanied by a post-response hyperpolarization. 3. DLH responses (smaller than those necessary to evoke firing) were accompanied by a stable decrease in GM. This decrease was usually more than could be accounted for by anomalous rectification of the membrane. 4. Small glutamate responses were accompanied by either a small decrease, no change or a small increase in GM. There was a biphasic change in GM during large responses: GM decreased during the rising phase and early part of the response plateau and thereafter increased as the depolarization was maintained. It is proposed that the high conductance state during glutamate application (but not the depolarization itself) is a manifestation of glutamate uptake. 5. Firing evoked by DLH was stable during very long applications of the drug. Firing evoked by glutamate was usually of short duration, despite the maintained depolarization. 6. No reversal potential for the DLH responses could be demonstrated, but the responses decreased in size both with hyperpolarization and depolarization of the membrane. A 'null point' of the response in the negative direction was found to be approximately -95 mV. 7. DLH resonses were insensitive to changes in the internal Cl concentration. When the external K concentration was increased by K+ ionophoresis, the DLH responses became smaller. It is concluded that the DLH response is probably mediated via a decrease in K+ conductance and that the availability of this conductance channel is potential dependent. 8. Changes in the sizes of evoked potentials (e.p.s.p.s, i.p.s.p.s and a.h.p.s) with DLH and glutamate responses were investigated. The size of each of these evoked potentials was inversely related to GM during the responses; thus they all showed stable increases during DLH responses. E.p.s.p.s recorded during DLH were of longer half-width and time-to-peak than the control, but there was no change in the maximum slope (V.sec-1). When e.p.s.p.s decreased in size with glutamate the time-to-peak remained constant. 9. Acidic amino acids have been implicated as natural excitatory transmitters. The consequence of our results for the mechanism of excitatory transmission is therefore discussed.", "contents": "The actions of excitatory amino acids on motoneurones in the feline spinal cord. 1. Combined recording or ionophoretic electrodes of the concentric type were used to investigate the depolarizing responses of DL-homocysteate (DLH) and L-glutamate in cat lumbar motoneurones. 2. Typically, DLH responses were slow both in onset and recovery, while glutamate responses were fast in onset and recovery and were frequently accompanied by a post-response hyperpolarization. 3. DLH responses (smaller than those necessary to evoke firing) were accompanied by a stable decrease in GM. This decrease was usually more than could be accounted for by anomalous rectification of the membrane. 4. Small glutamate responses were accompanied by either a small decrease, no change or a small increase in GM. There was a biphasic change in GM during large responses: GM decreased during the rising phase and early part of the response plateau and thereafter increased as the depolarization was maintained. It is proposed that the high conductance state during glutamate application (but not the depolarization itself) is a manifestation of glutamate uptake. 5. Firing evoked by DLH was stable during very long applications of the drug. Firing evoked by glutamate was usually of short duration, despite the maintained depolarization. 6. No reversal potential for the DLH responses could be demonstrated, but the responses decreased in size both with hyperpolarization and depolarization of the membrane. A 'null point' of the response in the negative direction was found to be approximately -95 mV. 7. DLH resonses were insensitive to changes in the internal Cl concentration. When the external K concentration was increased by K+ ionophoresis, the DLH responses became smaller. It is concluded that the DLH response is probably mediated via a decrease in K+ conductance and that the availability of this conductance channel is potential dependent. 8. Changes in the sizes of evoked potentials (e.p.s.p.s, i.p.s.p.s and a.h.p.s) with DLH and glutamate responses were investigated. The size of each of these evoked potentials was inversely related to GM during the responses; thus they all showed stable increases during DLH responses. E.p.s.p.s recorded during DLH were of longer half-width and time-to-peak than the control, but there was no change in the maximum slope (V.sec-1). When e.p.s.p.s decreased in size with glutamate the time-to-peak remained constant. 9. Acidic amino acids have been implicated as natural excitatory transmitters. The consequence of our results for the mechanism of excitatory transmission is therefore discussed."}
{"id": "PMID:224167", "title": "Transmission and contraction fatigue of rat motor units in relation to succinate dehydrogenase activity of motor unit fibres.", "content": "1. The fatigue in rat anterior tibial (a.t.) motor units was studied and related to microphotometric determinations of succinate dehydrogenase (SDH) activity of the motor unit muscle fibres. 2. Anterior tibial contains fast-twitch type II fibre units with an average contraction time of 11 msec and about 5% slow-twitch type I fibre units with an average contraction time of 20 msec. 3. In type II fibres stained for SDH, absorbance varied continuously from 0.046 to 0.569 and inversely to fibre size, except for the largest fibres. 4. Resistance to fatigue of fast motor units to 100 Hz intermittent stimulation varied continuously within a wide range in near linear relations to absorbance for SDH of unit fibres and inversely to tetanic tension, except for motor units with the largest fibres and the largest tetanic tension. 5. Neither resistance to fatigue nor SDH activity lent itself to any categorization of motor units or fibres into well demarcated functional or histochemical types, since both parameters varied continuously in the unit and fibre population of the muscle. 6. The direct relation between resistance to fatigue of fast-twitch motor units and SDH activity of unit fibres appeared valid for fatigue resistance of: (a) neuromuscular transmission, tested with 100 Hz intermittent stimulation which gave concomitant failure of electrical and mechanical response, (b) excitation--contraction coupling,  demonstrated by post-stimulatory depression of twitch tension with preserved maximum tetanus tension and action potential, and (c) contractile mechanism; excitation--contraction coupling?, tested with low frequency stimulation which gave decline of twitch and maximum tetanus tension with preserved action potential. 7. It is suggested that the endurance of each link in the chain of events leading to contraction, including neuromuscular junction and the excitation--contraction coupling system, is under aerobic conditions matched to the contractile capacity of the fibre expressed by its oxidative enzyme activity.", "contents": "Transmission and contraction fatigue of rat motor units in relation to succinate dehydrogenase activity of motor unit fibres. 1. The fatigue in rat anterior tibial (a.t.) motor units was studied and related to microphotometric determinations of succinate dehydrogenase (SDH) activity of the motor unit muscle fibres. 2. Anterior tibial contains fast-twitch type II fibre units with an average contraction time of 11 msec and about 5% slow-twitch type I fibre units with an average contraction time of 20 msec. 3. In type II fibres stained for SDH, absorbance varied continuously from 0.046 to 0.569 and inversely to fibre size, except for the largest fibres. 4. Resistance to fatigue of fast motor units to 100 Hz intermittent stimulation varied continuously within a wide range in near linear relations to absorbance for SDH of unit fibres and inversely to tetanic tension, except for motor units with the largest fibres and the largest tetanic tension. 5. Neither resistance to fatigue nor SDH activity lent itself to any categorization of motor units or fibres into well demarcated functional or histochemical types, since both parameters varied continuously in the unit and fibre population of the muscle. 6. The direct relation between resistance to fatigue of fast-twitch motor units and SDH activity of unit fibres appeared valid for fatigue resistance of: (a) neuromuscular transmission, tested with 100 Hz intermittent stimulation which gave concomitant failure of electrical and mechanical response, (b) excitation--contraction coupling,  demonstrated by post-stimulatory depression of twitch tension with preserved maximum tetanus tension and action potential, and (c) contractile mechanism; excitation--contraction coupling?, tested with low frequency stimulation which gave decline of twitch and maximum tetanus tension with preserved action potential. 7. It is suggested that the endurance of each link in the chain of events leading to contraction, including neuromuscular junction and the excitation--contraction coupling system, is under aerobic conditions matched to the contractile capacity of the fibre expressed by its oxidative enzyme activity."}
{"id": "PMID:224168", "title": "Some effects of hypertonic solution on the properties of spontaneous transmitter release in the hypogastric ganglia of guinea-pigs.", "content": "1. The effects of hypertonic solutions on spontaneous transmitter release at synapses in the hypogastric ganglia of guinea-pigs were studied using intracellular recording techniques. 2. Hypertonic solutions were found to cause a marked hyperpolarization of the ganglion cells and this was accompanied by an increase in both the threshold and input resistance of these cells. 3. The frequency of spontaneous quantal release was found to depend exponentially on the tonicity of the bathing solution with a 50% increase in tonicity producing a 7-9 fold increase in the frequency of release. 4. Hypertonic solutions were also found to increase the degree of bursting within the spontaneous process so that the proportion of multiquantal spontaneous potentials was found to be increased in such solutions. 5. Two different models, the 'charge-screening' model (Van der Kloot & Kita, 1973) and the 'Ca-increase' model (Shimoni, Alnaes & Rahamimoff, 1977), for the mechanism underlying the effects of hypertonic solution were considered.", "contents": "Some effects of hypertonic solution on the properties of spontaneous transmitter release in the hypogastric ganglia of guinea-pigs. 1. The effects of hypertonic solutions on spontaneous transmitter release at synapses in the hypogastric ganglia of guinea-pigs were studied using intracellular recording techniques. 2. Hypertonic solutions were found to cause a marked hyperpolarization of the ganglion cells and this was accompanied by an increase in both the threshold and input resistance of these cells. 3. The frequency of spontaneous quantal release was found to depend exponentially on the tonicity of the bathing solution with a 50% increase in tonicity producing a 7-9 fold increase in the frequency of release. 4. Hypertonic solutions were also found to increase the degree of bursting within the spontaneous process so that the proportion of multiquantal spontaneous potentials was found to be increased in such solutions. 5. Two different models, the 'charge-screening' model (Van der Kloot & Kita, 1973) and the 'Ca-increase' model (Shimoni, Alnaes & Rahamimoff, 1977), for the mechanism underlying the effects of hypertonic solution were considered."}
{"id": "PMID:224169", "title": "Dorsal root potentials and changes in extracellular potassium in the spinal cord of the frog.", "content": "1. In the present study changes in extracellular potassium, ([K]e), were recorded in the isolated spinal cord of the frog with glial cell recordings and K-selective micro-electrodes to test the hypothesis that elevations in [K]e during neuronal activity produce the dorsal root potential (d.r.p.). 2. Sucrose gap recording from the dorsal root (d.r.) was used to record responses to root stimulation and to exogenously applied K+. 3. Stimulation of the ventral root, which elicits a d.r.p. in the frog spinal cord, was not associated with any change in [K]e, suggesting that d.r.p.s produced by ventral root stimulation are not due to changes in [K]e. 4. The largest change in [K]e observed following single stimuli to the dorsal root was 0.4 mM. Such a change in [K]e, if evenly distributed, would depolarize the dorsal root by about 1 mV and yet the simultaneously recorded d.r.p. evoked by stimulating an adjacent dorsal root (d.r.-d.r.p.) was over 10 mV. 5. The time-to-peak of the glidal cell responses was 10 times that of the d.r.-d.r.p. Low frequency (1-10 Hz) d.r. stimulation caused a decremental summation of glial cell responses, while there was no summation in the d.r.-d.r.p. These results suggest that the d.r.p. produced by single d.r. stimulation is generated in large part by a mechanism other than a change in [K]e. 6. During high frequency d.r. stimulation, which evoked 6-8 mM increases in [K]e, the adjacent d.r. was depolarized to a greater extent than that produced by single stimuli. The magnitude of this depolarization was similar to that produced by applying a [K]e equivalent to that observed in the spinal cord during high frequency stimulation. Thus, a substantial component of the sustained d.r. depolarization during high frequency d.r. stimulation may result from changes in [K]e. 7. In the presence of magnesium, high frequency d.r. stimulation evoked a picrotoxin resistant depolarization of an adjacent d.r. whose magnitude correlated well with the changes in [K]e recorded in the spinal cord. 8. In the presence of picrotoxin a slow, long duration depolarization of the d.r. occurred following single stimuli to the adjacent d.r. and the appearance and time course of this response correlated well with the time course of changes in [K]e. 9. Addition of K+ to the Ringer solution in concentrations up to 12 mM had a facilitatory action on reflex activity in the frog spinal cord. 10 The present results suggest that although changes in [K]e play a relatively minor role in generating d.r.p.s. elicited by single d.r. stimulation, the sustained dorsal root depolarization evoked either by high frequency stimulation or by single stimuli in the presence of picrotoxin may be due to a considerable extent to [K]e.", "contents": "Dorsal root potentials and changes in extracellular potassium in the spinal cord of the frog. 1. In the present study changes in extracellular potassium, ([K]e), were recorded in the isolated spinal cord of the frog with glial cell recordings and K-selective micro-electrodes to test the hypothesis that elevations in [K]e during neuronal activity produce the dorsal root potential (d.r.p.). 2. Sucrose gap recording from the dorsal root (d.r.) was used to record responses to root stimulation and to exogenously applied K+. 3. Stimulation of the ventral root, which elicits a d.r.p. in the frog spinal cord, was not associated with any change in [K]e, suggesting that d.r.p.s produced by ventral root stimulation are not due to changes in [K]e. 4. The largest change in [K]e observed following single stimuli to the dorsal root was 0.4 mM. Such a change in [K]e, if evenly distributed, would depolarize the dorsal root by about 1 mV and yet the simultaneously recorded d.r.p. evoked by stimulating an adjacent dorsal root (d.r.-d.r.p.) was over 10 mV. 5. The time-to-peak of the glidal cell responses was 10 times that of the d.r.-d.r.p. Low frequency (1-10 Hz) d.r. stimulation caused a decremental summation of glial cell responses, while there was no summation in the d.r.-d.r.p. These results suggest that the d.r.p. produced by single d.r. stimulation is generated in large part by a mechanism other than a change in [K]e. 6. During high frequency d.r. stimulation, which evoked 6-8 mM increases in [K]e, the adjacent d.r. was depolarized to a greater extent than that produced by single stimuli. The magnitude of this depolarization was similar to that produced by applying a [K]e equivalent to that observed in the spinal cord during high frequency stimulation. Thus, a substantial component of the sustained d.r. depolarization during high frequency d.r. stimulation may result from changes in [K]e. 7. In the presence of magnesium, high frequency d.r. stimulation evoked a picrotoxin resistant depolarization of an adjacent d.r. whose magnitude correlated well with the changes in [K]e recorded in the spinal cord. 8. In the presence of picrotoxin a slow, long duration depolarization of the d.r. occurred following single stimuli to the adjacent d.r. and the appearance and time course of this response correlated well with the time course of changes in [K]e. 9. Addition of K+ to the Ringer solution in concentrations up to 12 mM had a facilitatory action on reflex activity in the frog spinal cord. 10 The present results suggest that although changes in [K]e play a relatively minor role in generating d.r.p.s. elicited by single d.r. stimulation, the sustained dorsal root depolarization evoked either by high frequency stimulation or by single stimuli in the presence of picrotoxin may be due to a considerable extent to [K]e."}
{"id": "PMID:224171", "title": "Relation between catecholamine-induced cyclic AMP changes and hyperpolarization in isolated rat sympathetic ganglia.", "content": "1. The effect of catecholamines on cyclic adenosine 3'5'-monophosphate (cyclic AMP) production in isolated rat superior cervical ganglia has been measured under experimental conditions in which they also produce ganglion hyperpolarization.2. (+/-)Isoprenaline (1 muM) increased cyclic AMP levels by 8-100 times after 15 min incubation at 25 degrees C. Half-maximal stimulation occurred at about 0.03 muM. This was due to stimulation of beta-receptors, since it was prevented by 1 muM-propranolol but not by 1 muM-phentolamine.3. The alpha-agonists phenylephrine (100 muM), dopamine (100 muM) and clonidine (1 muM) did not produce a detectable increase in ganglionic cyclic AMP. Dopamine (100 muM) was also ineffective at 37 degrees C in the presence of 10 mM-theophylline.4. Exogenous cyclic AMP (0.01-1 mM) hyperpolarized the ganglion. This effect was replicated by other adenosine compounds, most effectively by adenosine and by adenosine 5'-monophosphate, and was antagonized by theophylline. Dibutyryl cyclic AMP was weaker than cyclic AMP.5. Neither theophylline nor the non-xanthine phosphodiesterase inhibitor, Ro 20-1724, enhanced the hyperpolarizing actions of noradrenaline or dopamine.6. Since catecholamine-induced hyperpolarization of the isolated rat ganglion is induced via alpha-receptors, whereas cyclic AMP-production is induced via beta-receptors, it is concluded that cyclic AMP is unlikely to mediate the hyperpolarization. The effect of exogenous cyclic AMP may be due to an action on external adenosine-receptors.", "contents": "Relation between catecholamine-induced cyclic AMP changes and hyperpolarization in isolated rat sympathetic ganglia. 1. The effect of catecholamines on cyclic adenosine 3'5'-monophosphate (cyclic AMP) production in isolated rat superior cervical ganglia has been measured under experimental conditions in which they also produce ganglion hyperpolarization.2. (+/-)Isoprenaline (1 muM) increased cyclic AMP levels by 8-100 times after 15 min incubation at 25 degrees C. Half-maximal stimulation occurred at about 0.03 muM. This was due to stimulation of beta-receptors, since it was prevented by 1 muM-propranolol but not by 1 muM-phentolamine.3. The alpha-agonists phenylephrine (100 muM), dopamine (100 muM) and clonidine (1 muM) did not produce a detectable increase in ganglionic cyclic AMP. Dopamine (100 muM) was also ineffective at 37 degrees C in the presence of 10 mM-theophylline.4. Exogenous cyclic AMP (0.01-1 mM) hyperpolarized the ganglion. This effect was replicated by other adenosine compounds, most effectively by adenosine and by adenosine 5'-monophosphate, and was antagonized by theophylline. Dibutyryl cyclic AMP was weaker than cyclic AMP.5. Neither theophylline nor the non-xanthine phosphodiesterase inhibitor, Ro 20-1724, enhanced the hyperpolarizing actions of noradrenaline or dopamine.6. Since catecholamine-induced hyperpolarization of the isolated rat ganglion is induced via alpha-receptors, whereas cyclic AMP-production is induced via beta-receptors, it is concluded that cyclic AMP is unlikely to mediate the hyperpolarization. The effect of exogenous cyclic AMP may be due to an action on external adenosine-receptors."}
{"id": "PMID:224172", "title": "Voltage clamping of unparalysed cut rat diaphragm for study of transmitter release.", "content": "1. As a result of the cutting procedure there is a decrease in the membrane potential, input resistance, and space constant of the rat diaphragm, and there is no contraction when the phrenic nerve is stimulated. While the reversal potential of  end-plate currents in cut preparations appears normal, the size of miniature end-plate currents (m.e.p.c.s.) is slightly decreased. 2. An increase in the external concentration of potassium from 2.5 to 10.0 mM results only in a minor change (less than 5%) in statistical parameters of transmitter release (m, n and p). The size of m.e.p.c. is also almost unchanged. 3. A decrease in temperature from 37 degrees to 15 degrees C resulted in a decrease of m, n and p; however, the values are less than 25% smaller at 25 degrees C than at 37 degrees C. The size of m.e.p.c.s is very insensitive to changes in temperature. 4. As previously reported for the frog neuromuscular junction, changes in muscle membrane potential of cut and uncut rat diaphragm due to voltage clamping affect the frequency of m.e.p.c.s only in medium with raised external K concentration. The dependence of frequency of m.e.p.c.s on muscle membrane potential is remarkably similar in cut and uncut preparations. Evoked release in cut preparation in normal medium is not affected by the change in muscle membrane potential.", "contents": "Voltage clamping of unparalysed cut rat diaphragm for study of transmitter release. 1. As a result of the cutting procedure there is a decrease in the membrane potential, input resistance, and space constant of the rat diaphragm, and there is no contraction when the phrenic nerve is stimulated. While the reversal potential of  end-plate currents in cut preparations appears normal, the size of miniature end-plate currents (m.e.p.c.s.) is slightly decreased. 2. An increase in the external concentration of potassium from 2.5 to 10.0 mM results only in a minor change (less than 5%) in statistical parameters of transmitter release (m, n and p). The size of m.e.p.c. is also almost unchanged. 3. A decrease in temperature from 37 degrees to 15 degrees C resulted in a decrease of m, n and p; however, the values are less than 25% smaller at 25 degrees C than at 37 degrees C. The size of m.e.p.c.s is very insensitive to changes in temperature. 4. As previously reported for the frog neuromuscular junction, changes in muscle membrane potential of cut and uncut rat diaphragm due to voltage clamping affect the frequency of m.e.p.c.s only in medium with raised external K concentration. The dependence of frequency of m.e.p.c.s on muscle membrane potential is remarkably similar in cut and uncut preparations. Evoked release in cut preparation in normal medium is not affected by the change in muscle membrane potential."}
{"id": "PMID:224173", "title": "Change of statistical parameters of transmitter release during various kinetic tests in unparalysed voltage-clamped rat diaphragm.", "content": "1. The statistical nature of transmitter release was studied in unparalysed cut rat diaphragm using a voltage clamp technique at room temperature (23 degrees C). 2. While the binomial distribution described observed amplitude histograms well, the Poisson distribution was clearly inadequate. Values of m ranged from 40 to 45, while values for n varied from 45 to 53 and p was between 0.82 and 0.90. 3. Estimation of the probability of release from the transient decay of e.p.c.s in short tetanic trains (11 pulses, 150 Hz) gave values of p from 0.031 to 0.054, which are more than one order of magnitude lower than statistical estimates. 4. As a result of the short tetanic stimulation (5 pulses, 20, 50 and 100 Hz) there is an initial transient facilitation which afterwards becomes masked by depression. Statistical analysis suggests that the changes in the average numbers of quanta released (m) could be attributed to the change in the immediately available store (n). 5. During long tetanic stimulation (4000 pulses, 10-100 Hz) statistical analysis suggests that the decrease in the average number of quanta released (m) could be attributed almost entirely to the decrease in the immediately available store (n). The probability of release (p) decreased only slightly. The extent of the post-tetanic potentiation indicates that it cannot be explained on the grounds of increased probability of release (p) only. There should be an increase as well in the immediately available store (n). 6. It is suggested that while depression is most likely caused by the depletion of the immediately available store due to insufficient replenishment, the facilitation is probably caused by the increase in the capacity of the immediately available store to contain transmitter.", "contents": "Change of statistical parameters of transmitter release during various kinetic tests in unparalysed voltage-clamped rat diaphragm. 1. The statistical nature of transmitter release was studied in unparalysed cut rat diaphragm using a voltage clamp technique at room temperature (23 degrees C). 2. While the binomial distribution described observed amplitude histograms well, the Poisson distribution was clearly inadequate. Values of m ranged from 40 to 45, while values for n varied from 45 to 53 and p was between 0.82 and 0.90. 3. Estimation of the probability of release from the transient decay of e.p.c.s in short tetanic trains (11 pulses, 150 Hz) gave values of p from 0.031 to 0.054, which are more than one order of magnitude lower than statistical estimates. 4. As a result of the short tetanic stimulation (5 pulses, 20, 50 and 100 Hz) there is an initial transient facilitation which afterwards becomes masked by depression. Statistical analysis suggests that the changes in the average numbers of quanta released (m) could be attributed to the change in the immediately available store (n). 5. During long tetanic stimulation (4000 pulses, 10-100 Hz) statistical analysis suggests that the decrease in the average number of quanta released (m) could be attributed almost entirely to the decrease in the immediately available store (n). The probability of release (p) decreased only slightly. The extent of the post-tetanic potentiation indicates that it cannot be explained on the grounds of increased probability of release (p) only. There should be an increase as well in the immediately available store (n). 6. It is suggested that while depression is most likely caused by the depletion of the immediately available store due to insufficient replenishment, the facilitation is probably caused by the increase in the capacity of the immediately available store to contain transmitter."}
{"id": "PMID:224174", "title": "Presynaptic action of curare.", "content": "1. As a result of a conditioning phrenic nerve stimulus, end-plate currents (e.p.c.s) in a voltage clamped uncurarized cut diaphragm show a facilitation which reaches its maximum at 30-40 msec and subsequently decays with a time constant from 150 to 200 msec. In curarized (cut or uncut) diaphragms, however, the conditioning stimulus causes a depression which reaches its maximal value at 10 msec and then decays slowly with a time constant of about 3 sec. This indicates that curare strongly interferes with the process of transmitter release. 2. The presynaptic action of curare is also evident if short tetanic trains are given. In uncurarized preparations e.p.c.s decay in size much more slowly than in curarized preparations, and usually show a transient facilitation. 3. These results can be explained in terms of a model where curare blocks presynaptic depolarizing action of ACh. As a result of this presumed curare action a small increase in Ca permeability and subsequent entry of Ca associated with depolarization are also blocked, and the facilitation resulting from that entry of Ca is abolished.", "contents": "Presynaptic action of curare. 1. As a result of a conditioning phrenic nerve stimulus, end-plate currents (e.p.c.s) in a voltage clamped uncurarized cut diaphragm show a facilitation which reaches its maximum at 30-40 msec and subsequently decays with a time constant from 150 to 200 msec. In curarized (cut or uncut) diaphragms, however, the conditioning stimulus causes a depression which reaches its maximal value at 10 msec and then decays slowly with a time constant of about 3 sec. This indicates that curare strongly interferes with the process of transmitter release. 2. The presynaptic action of curare is also evident if short tetanic trains are given. In uncurarized preparations e.p.c.s decay in size much more slowly than in curarized preparations, and usually show a transient facilitation. 3. These results can be explained in terms of a model where curare blocks presynaptic depolarizing action of ACh. As a result of this presumed curare action a small increase in Ca permeability and subsequent entry of Ca associated with depolarization are also blocked, and the facilitation resulting from that entry of Ca is abolished."}
{"id": "PMID:224175", "title": "Effects of cold adaptation and re-adaptation upon the mitochondrial phospholipids of brown adipose tissue.", "content": "1. A study of the mitochondrial phospholipids, phospholipid fatty acid patterns and enzyme activities was investigated in brown tissue (B.A.T.) from rats chronically exposed to cold and/or treated with thyroxine. 2. The total activities of the oxidative enzymes were increased after cold exposure, but not after thyroxine treatment. 3. Cold exposure increased the amount of phosphatidylethanolamine, phosphatidylcholine, cardiolipin and lysophospholipids, the effect being greatest for phosphatidylethanolamine. At the same time, there were marked alterations in the fatty acid composition of the mitochondrial phospholipids (decrease of palmitic, palmitoleic and oleic acids ; increase of stearic, linoleic and arachidonic acids). 4. All these cold-induced alterations were reversed by re-adaptation of the animal to a normal temperature range. 5. The alterations of the fatty acid composition of phospholipids could be explained by changes in the rate of individual fatty acid biosynthesis.", "contents": "Effects of cold adaptation and re-adaptation upon the mitochondrial phospholipids of brown adipose tissue. 1. A study of the mitochondrial phospholipids, phospholipid fatty acid patterns and enzyme activities was investigated in brown tissue (B.A.T.) from rats chronically exposed to cold and/or treated with thyroxine. 2. The total activities of the oxidative enzymes were increased after cold exposure, but not after thyroxine treatment. 3. Cold exposure increased the amount of phosphatidylethanolamine, phosphatidylcholine, cardiolipin and lysophospholipids, the effect being greatest for phosphatidylethanolamine. At the same time, there were marked alterations in the fatty acid composition of the mitochondrial phospholipids (decrease of palmitic, palmitoleic and oleic acids ; increase of stearic, linoleic and arachidonic acids). 4. All these cold-induced alterations were reversed by re-adaptation of the animal to a normal temperature range. 5. The alterations of the fatty acid composition of phospholipids could be explained by changes in the rate of individual fatty acid biosynthesis."}
{"id": "PMID:224176", "title": "[Hypothalamic influence on differentiation of the immunoreactive ACTH beta-LPH, alpha- and beta-endorphin containing cells in adenohypophysial primordia of rat fetus in organ culture (author's transl)].", "content": "Adenohypophysial primordia were isolated in rat fetuses from day 12.5 to day 15.5 of gestation. The organ culture employed for maintenance of the primordia was made up according to Watanabe et al. (1973). The fixation of primordia in Bouin Hollande's solution was performed after 9, 8, 7 or 6 days of culture when the normal duration of pregnancy was achieved. The cultivated primordia were immunologically studied using different antisera: anti-alpha(17-39)ACTH, anti-beta(1-24)ACTH, anti-beta-LPH, anti-alpha and anti-beta-endorphins, with immunoperoxidase or immunofluorescence techniques, including control experiments of the specificity of the antisera. A similar study was performed on pituitaries removed from normal rat fetuses from day 16.5 of gestation and each day up to birth, and fixated immediately. In vivo the first cells reacting with all the antisera used in this study were observed on day 16.5 of gestation; their number increased during gestation (Fig. 1 A, B and C). Immunoreactive cells with the different antisera could be detected in primordia isolated on day 12.5 of gestation after 9 days of culture. Numerous groups of cells were observed in primordia of older fetuses (Fig. 2 A and B). These data indicate that the corticotropic cells in rat fetuses could start to be differentiated without stimuli from the hypothalamus since primordia were isolated before the appearance of this cell type in normal rat fetuses and before the differentiation of the hypothalamus. The presence of ACTH and other peptides such as beta-LPH or beta-endorphin would support the hypothesis of a common precursor in this cell type existing early in gestation. Similar results were obtained in human fetuses.", "contents": "[Hypothalamic influence on differentiation of the immunoreactive ACTH beta-LPH, alpha- and beta-endorphin containing cells in adenohypophysial primordia of rat fetus in organ culture (author's transl)]. Adenohypophysial primordia were isolated in rat fetuses from day 12.5 to day 15.5 of gestation. The organ culture employed for maintenance of the primordia was made up according to Watanabe et al. (1973). The fixation of primordia in Bouin Hollande's solution was performed after 9, 8, 7 or 6 days of culture when the normal duration of pregnancy was achieved. The cultivated primordia were immunologically studied using different antisera: anti-alpha(17-39)ACTH, anti-beta(1-24)ACTH, anti-beta-LPH, anti-alpha and anti-beta-endorphins, with immunoperoxidase or immunofluorescence techniques, including control experiments of the specificity of the antisera. A similar study was performed on pituitaries removed from normal rat fetuses from day 16.5 of gestation and each day up to birth, and fixated immediately. In vivo the first cells reacting with all the antisera used in this study were observed on day 16.5 of gestation; their number increased during gestation (Fig. 1 A, B and C). Immunoreactive cells with the different antisera could be detected in primordia isolated on day 12.5 of gestation after 9 days of culture. Numerous groups of cells were observed in primordia of older fetuses (Fig. 2 A and B). These data indicate that the corticotropic cells in rat fetuses could start to be differentiated without stimuli from the hypothalamus since primordia were isolated before the appearance of this cell type in normal rat fetuses and before the differentiation of the hypothalamus. The presence of ACTH and other peptides such as beta-LPH or beta-endorphin would support the hypothesis of a common precursor in this cell type existing early in gestation. Similar results were obtained in human fetuses."}
{"id": "PMID:224184", "title": "The defense mechanism of splitting: developmental origins, effects on staff, recommendations for nursing care.", "content": "Splitting as a predominant defense mechanism is used by a large number of people. It is characterized by projection of good and bad qualities onto people in the environment and malformed ego functioning. Nurses need to understand the developmental origins, formation of ego deficits and defense mechanism of splitting so that they can care for these people. Effective nursing care is dependent on leadership which anticipates splitting, maintains a cohesive staff group and intervenes appropriately. Limit setting provides the most effective treatment modality as it supplies the missing internal function of the deficient ego. With this use of limit setting staff will prevent splitting and foster socially acceptable behavior. This will have a dual effect of beginning ego reconstruction and increasing self-esteem for the patient and treatment success for the staff.", "contents": "The defense mechanism of splitting: developmental origins, effects on staff, recommendations for nursing care. Splitting as a predominant defense mechanism is used by a large number of people. It is characterized by projection of good and bad qualities onto people in the environment and malformed ego functioning. Nurses need to understand the developmental origins, formation of ego deficits and defense mechanism of splitting so that they can care for these people. Effective nursing care is dependent on leadership which anticipates splitting, maintains a cohesive staff group and intervenes appropriately. Limit setting provides the most effective treatment modality as it supplies the missing internal function of the deficient ego. With this use of limit setting staff will prevent splitting and foster socially acceptable behavior. This will have a dual effect of beginning ego reconstruction and increasing self-esteem for the patient and treatment success for the staff."}
{"id": "PMID:224188", "title": "Adenosine 3'5'-monophosphate phosphodiesterase of buffalo spermatozoa.", "content": "The cyclic AMP-phosphodiesterase (EC 3.1.4.17) of buffalo spermatozoa is distributed in the head, mid-piece and tail fractions and has multiple forms, 70% of which is in the bound form. The bound enzyme was not solubilized by Triton X-100, lubrol or hyamine 2389. Kinetic measurements of the soluble enzyme showed two apparent Km values for low and high cAMP concentrations, i.e. 4.5 and 100 micro M with Vmax values of 0.25 and 2.0 nmol cAMP hydrolysed min-1 mg protein-1. The bound enzyme had an apparent Km of 66.6 microM with a Vmax of 0.75 nmol cAMP hydrolysed min-1 mg protein-1. The pH for optimum enzyme activity was 7.5 and Mg2+ was essential for the activity of the soluble and bound enzymes. Methylxanthines, ATP, ADP and ppi inhibited the soluble and bound enzymes, ATP being the most potent inhibitor.", "contents": "Adenosine 3'5'-monophosphate phosphodiesterase of buffalo spermatozoa. The cyclic AMP-phosphodiesterase (EC 3.1.4.17) of buffalo spermatozoa is distributed in the head, mid-piece and tail fractions and has multiple forms, 70% of which is in the bound form. The bound enzyme was not solubilized by Triton X-100, lubrol or hyamine 2389. Kinetic measurements of the soluble enzyme showed two apparent Km values for low and high cAMP concentrations, i.e. 4.5 and 100 micro M with Vmax values of 0.25 and 2.0 nmol cAMP hydrolysed min-1 mg protein-1. The bound enzyme had an apparent Km of 66.6 microM with a Vmax of 0.75 nmol cAMP hydrolysed min-1 mg protein-1. The pH for optimum enzyme activity was 7.5 and Mg2+ was essential for the activity of the soluble and bound enzymes. Methylxanthines, ATP, ADP and ppi inhibited the soluble and bound enzymes, ATP being the most potent inhibitor."}
{"id": "PMID:224195", "title": "Suppression of the hypothalamic-pituitary-adrenal axis after subcutaneous cortisone acetate administration in rats.", "content": "Groups of female rats were injected daily for 14 days with 10 mg of cortisone acetate subcutaneously, to study the mechanisms of glucocorticoid suppression on the hypothalamic-pituitary-adrenal axis. Pituitary adrenocorticotropic hormone (ACTH) content, plasma ACTH, adrenal venous corticosterone, adrenal weights, and the catabolic effects on body weight were studied simultaneously (under stressful and non-stressful conditions) before, during, and up to six weeks after cortisone. This study confirmed the results of other investigators that cortisone acetate caused catabolic weight loss and adrenal atrophy, but it was noted to persist up to six weeks after the injections. Glucocorticoid acetate was more effective in causing ACTH-axis suppression than succinate or phosphate preparations, and the effects were dose and time related. Significant depletion of pituitary ACTH content, suppression of plasma ACTH, and corticosterone secretion occurred five to seven days after beginning cortisone acetate (p=<0.001); it was continuous throughout the injection schedule (p=<0.001); it remained for two to four weeks after the cortisone was discontinued (p=<0.001). The animals showed minimum plasma ACTH responsiveness to severe acute stress during this two to four-week suppression phase, but rapid recovery occurred thereafter. Plasma ACTH was undetectable up to six weeks post-cortisone when the animals were not under stress. This may be related to residual cortisone acetate found at the injection sites, or to an altered or different ACTH-axis control mechanism. The sequence of events during recovery from cortisone suppression appeared to be (1) repletion of corticotrophin-releasing hormone (by inference), (2) repletion of pituitary ACTH content, (3) secretion of plasma ACTH, (4) reversal of adrenal atrophy, and (5) subsequent secretion of corticosterone.", "contents": "Suppression of the hypothalamic-pituitary-adrenal axis after subcutaneous cortisone acetate administration in rats. Groups of female rats were injected daily for 14 days with 10 mg of cortisone acetate subcutaneously, to study the mechanisms of glucocorticoid suppression on the hypothalamic-pituitary-adrenal axis. Pituitary adrenocorticotropic hormone (ACTH) content, plasma ACTH, adrenal venous corticosterone, adrenal weights, and the catabolic effects on body weight were studied simultaneously (under stressful and non-stressful conditions) before, during, and up to six weeks after cortisone. This study confirmed the results of other investigators that cortisone acetate caused catabolic weight loss and adrenal atrophy, but it was noted to persist up to six weeks after the injections. Glucocorticoid acetate was more effective in causing ACTH-axis suppression than succinate or phosphate preparations, and the effects were dose and time related. Significant depletion of pituitary ACTH content, suppression of plasma ACTH, and corticosterone secretion occurred five to seven days after beginning cortisone acetate (p=<0.001); it was continuous throughout the injection schedule (p=<0.001); it remained for two to four weeks after the cortisone was discontinued (p=<0.001). The animals showed minimum plasma ACTH responsiveness to severe acute stress during this two to four-week suppression phase, but rapid recovery occurred thereafter. Plasma ACTH was undetectable up to six weeks post-cortisone when the animals were not under stress. This may be related to residual cortisone acetate found at the injection sites, or to an altered or different ACTH-axis control mechanism. The sequence of events during recovery from cortisone suppression appeared to be (1) repletion of corticotrophin-releasing hormone (by inference), (2) repletion of pituitary ACTH content, (3) secretion of plasma ACTH, (4) reversal of adrenal atrophy, and (5) subsequent secretion of corticosterone."}
{"id": "PMID:224196", "title": "Relation of steroids to liver oncogenesis.", "content": "Experience with pathological material from 150 women with liver tumors is reviewed. The features of liver cell adenoma and focal nodular hyperplasia are sufficiently different that the vast majority of the benign tumors can be easily subclassified. Although most occurred in women ingesting steroids, the wide usage of oral contraceptives makes it difficult to prove a causative role. Nineteen of the tumors were malignant and, to date, 12 of those patients have died of their disease. Since hepatomas are much more common than benign liver tumors, one must be even more circumspect in indicting steroids in their causation. In this group of women none had cirrhosis, whereas in the general population cirrhosis is a very common precedent lesion. Further investigation of estrogens and primary liver carcinoma would be timely.", "contents": "Relation of steroids to liver oncogenesis. Experience with pathological material from 150 women with liver tumors is reviewed. The features of liver cell adenoma and focal nodular hyperplasia are sufficiently different that the vast majority of the benign tumors can be easily subclassified. Although most occurred in women ingesting steroids, the wide usage of oral contraceptives makes it difficult to prove a causative role. Nineteen of the tumors were malignant and, to date, 12 of those patients have died of their disease. Since hepatomas are much more common than benign liver tumors, one must be even more circumspect in indicting steroids in their causation. In this group of women none had cirrhosis, whereas in the general population cirrhosis is a very common precedent lesion. Further investigation of estrogens and primary liver carcinoma would be timely."}
{"id": "PMID:224197", "title": "Role of oral contraceptive agents in the pathogenesis of liver tumors.", "content": "Since the introduction of oral contraceptive steroids in 1960 there has been a sharp increase in the incidence of benign liver tumors. Epidemiologic and other evidence links focal nodular hyperplasia and hepatic cell adenoma to the use of these agents. The risk increases with long-term exposure. The majority of patients were less than 35 years old. Most patients were exposed to mestranol (ME) alone or alternately with ethinylestradiol, both synthetic steroidal estrogens. Inability to demethylate ME in the smooth endoplasmic reticulum of hepatocytes may allow massive accumulation of oncogenic metabolites. This is probably a pharmacogenetic variable in a small number of women. Cholestasis, hypervascularity, induction of intracellular enzyme systems, thrombogenesis, and thickening of arterial and venous walls are other known effects of synthetic estrogens and progestogens. All may contribute to the pathogenesis of liver tumors. Many patients are asymptomatic until there is rapid expansion of the tumor. Pain occurs when Glisson's capsule stretches. Intrahepatic bleeding and liver rupture are common sequelae. Ligation of the hepatic artery may be lifesaving in the face of exsanguinating liver bleeding. Reports of regression with observation alone are encouraging. Instances of progression of unresected adenomas to rupture during subsequent pregnancy dictate avoidance of sex steroids in patients with hepatic neoplasia. Sonography, computerized axial tomography, radionuclide scans, and selective celiohepatic angiography are useful methods for the diagnosis of liver tumor in the symptomatic patient. There is a primary need to develop biochemical methods for detecting patients at risk for developing liver tumors. Epidemiologic research and central reporting of case histories are needed in the search for common factors.", "contents": "Role of oral contraceptive agents in the pathogenesis of liver tumors. Since the introduction of oral contraceptive steroids in 1960 there has been a sharp increase in the incidence of benign liver tumors. Epidemiologic and other evidence links focal nodular hyperplasia and hepatic cell adenoma to the use of these agents. The risk increases with long-term exposure. The majority of patients were less than 35 years old. Most patients were exposed to mestranol (ME) alone or alternately with ethinylestradiol, both synthetic steroidal estrogens. Inability to demethylate ME in the smooth endoplasmic reticulum of hepatocytes may allow massive accumulation of oncogenic metabolites. This is probably a pharmacogenetic variable in a small number of women. Cholestasis, hypervascularity, induction of intracellular enzyme systems, thrombogenesis, and thickening of arterial and venous walls are other known effects of synthetic estrogens and progestogens. All may contribute to the pathogenesis of liver tumors. Many patients are asymptomatic until there is rapid expansion of the tumor. Pain occurs when Glisson's capsule stretches. Intrahepatic bleeding and liver rupture are common sequelae. Ligation of the hepatic artery may be lifesaving in the face of exsanguinating liver bleeding. Reports of regression with observation alone are encouraging. Instances of progression of unresected adenomas to rupture during subsequent pregnancy dictate avoidance of sex steroids in patients with hepatic neoplasia. Sonography, computerized axial tomography, radionuclide scans, and selective celiohepatic angiography are useful methods for the diagnosis of liver tumor in the symptomatic patient. There is a primary need to develop biochemical methods for detecting patients at risk for developing liver tumors. Epidemiologic research and central reporting of case histories are needed in the search for common factors."}
{"id": "PMID:224198", "title": "Survey of primary liver tumors and oral contraceptive use.", "content": "The American College of Surgeons' survey data on 378 female and 165 male cases of primary liver tumors reported by 477 hospitals in the United States during 1970--1975 are presented. In males, 91.5% of the tumors were malignant, confirming the rarity of benign liver tumors in males. Among females, 43.9% were malignant and 56.1% were benign. Of the 212 benign tumors, 96 were hepatic cell adenomas and 58 were focal nodular hyperplasias. A positive history of oral contraceptive use was found in nearly half of all tumors, 65% of benign tumors, 74% of hepatic cell adenomas, and 74% of focal nodular hyperplasias. High frequencies of benign tumors were observed in the age group 20--30 yr. More than 80% of the tumors in this age group were found in oral contraceptive users. Symptomatology was more severe among users. No case of intraperitoneal bleeding was observed in nonusers. The findings confirm the suggested association between use of oral contraceptives and hepatic cell adenomas and focal nodular hyperplasias.", "contents": "Survey of primary liver tumors and oral contraceptive use. The American College of Surgeons' survey data on 378 female and 165 male cases of primary liver tumors reported by 477 hospitals in the United States during 1970--1975 are presented. In males, 91.5% of the tumors were malignant, confirming the rarity of benign liver tumors in males. Among females, 43.9% were malignant and 56.1% were benign. Of the 212 benign tumors, 96 were hepatic cell adenomas and 58 were focal nodular hyperplasias. A positive history of oral contraceptive use was found in nearly half of all tumors, 65% of benign tumors, 74% of hepatic cell adenomas, and 74% of focal nodular hyperplasias. High frequencies of benign tumors were observed in the age group 20--30 yr. More than 80% of the tumors in this age group were found in oral contraceptive users. Symptomatology was more severe among users. No case of intraperitoneal bleeding was observed in nonusers. The findings confirm the suggested association between use of oral contraceptives and hepatic cell adenomas and focal nodular hyperplasias."}
{"id": "PMID:224199", "title": "Role of hepatitis B virus in primary liver cancer.", "content": "There is an excess prevalence of markers of active infection with hepatitis B virus in patients with primary liver cancer in many parts of the world. Early age of infection with hepatitis B virus is likely to be an important factor, resulting in persistent infection that may progress to chronic liver damage. Results of recent experimental studies are consistent with integration of hepatitis B viral DNA with host cell DNA molecules. It is likely that primary liver cancer is the cumulative result of several cofactors including infection with hepatitis B virus; genetic, immunologic, hormonal, and nutritional factors; and environmental factors including mycotoxins and chemical carcinogens.", "contents": "Role of hepatitis B virus in primary liver cancer. There is an excess prevalence of markers of active infection with hepatitis B virus in patients with primary liver cancer in many parts of the world. Early age of infection with hepatitis B virus is likely to be an important factor, resulting in persistent infection that may progress to chronic liver damage. Results of recent experimental studies are consistent with integration of hepatitis B viral DNA with host cell DNA molecules. It is likely that primary liver cancer is the cumulative result of several cofactors including infection with hepatitis B virus; genetic, immunologic, hormonal, and nutritional factors; and environmental factors including mycotoxins and chemical carcinogens."}
{"id": "PMID:224200", "title": "Precancerous changes in the human liver.", "content": "Knowledge of the cellular changes that lead to hepatic neoplasia in humans is limited. Cirrhosis is a common antecedent or accompaniment of liver cell carcinoma and it seems that both its etiology and its time of duration are relevant risk factors. Many cellular changes have been observed in patients and among populations considered to be at risk. Of these, liver cell dysplasia is the most striking, and studies of its prevalence, natural history, and association with particular forms of cirrhosis suggest that it is a precancerous change. Bile duct carcinoma may follow infestation with liver flukes and duct epithelial hyperplasia is present before the development of cancer. Angiosarcoma from several causes is commonly preceded by a peculiar fibrosis, vascular changes, and Kupffer cell hyperplasia.", "contents": "Precancerous changes in the human liver. Knowledge of the cellular changes that lead to hepatic neoplasia in humans is limited. Cirrhosis is a common antecedent or accompaniment of liver cell carcinoma and it seems that both its etiology and its time of duration are relevant risk factors. Many cellular changes have been observed in patients and among populations considered to be at risk. Of these, liver cell dysplasia is the most striking, and studies of its prevalence, natural history, and association with particular forms of cirrhosis suggest that it is a precancerous change. Bile duct carcinoma may follow infestation with liver flukes and duct epithelial hyperplasia is present before the development of cancer. Angiosarcoma from several causes is commonly preceded by a peculiar fibrosis, vascular changes, and Kupffer cell hyperplasia."}
{"id": "PMID:224201", "title": "Pathology of primary liver cancer.", "content": "After a brief survey of the factors that play a role in the etiopathogenesis of human hepatocellular carcinomas, a detailed description is given of the macroscopic and microscopic features of human liver cancers as well as their association with cirrhosis. The ultrastructural features of liver cancers of various degrees of differentiation are described. The mode of spread, metastasis formation of primary liver cancers, and most frequent causes of death of liver cancer patients are reviewed.", "contents": "Pathology of primary liver cancer. After a brief survey of the factors that play a role in the etiopathogenesis of human hepatocellular carcinomas, a detailed description is given of the macroscopic and microscopic features of human liver cancers as well as their association with cirrhosis. The ultrastructural features of liver cancers of various degrees of differentiation are described. The mode of spread, metastasis formation of primary liver cancers, and most frequent causes of death of liver cancer patients are reviewed."}
{"id": "PMID:224202", "title": "Biochemical strategy of hepatomas.", "content": "An insight into the ordered pattern of enzymatic and biochemical imbalance of cancer cells was made possible, at least in part, by the molecular correlation concept, the concept of key enzymes, and the use of biological model systems. With these approaches the pattern of gene expression in neoplasia can be studied in terms of the activities of key enzymes and their linking with neoplastic transformation and progression. An ordered pattern of biochemical imbalance was recognized in carbohydrate, pentose phosphate, purine, pyrimidine, DNA, and polyamine metabolism and in other biochemical areas. Current work is directed to clarifying the enzymology and metabolic pattern of thymidine metabolism and CTP biosynthesis since these areas are of particular importance in selective chemotherapy and rescue. The activities of key enzymes in thymidine metabolism have been correlated with the growth rates in a spectrum of hepatomas. Increases in the activities of four key enzymes in CTP biosynthesis appear to be specific to neoplasia because no similar pattern was observed in the normal adult resting or regenerating liver or in the fetal and developing liver. The overall pattern discovered in transplantable rat hepatomas applies to other rodent tumors. It is of particular importance that the pattern of biochemical imbalance is also applicable to human hepatocellular carcinomas. With the recognition of the ordered pattern of reprogramming of gene expression in hepatomas, the path is open for the development of sensitive assays for biochemical diagnosis of liver tumors and for a rational design of selective chemotherapy and rescue.", "contents": "Biochemical strategy of hepatomas. An insight into the ordered pattern of enzymatic and biochemical imbalance of cancer cells was made possible, at least in part, by the molecular correlation concept, the concept of key enzymes, and the use of biological model systems. With these approaches the pattern of gene expression in neoplasia can be studied in terms of the activities of key enzymes and their linking with neoplastic transformation and progression. An ordered pattern of biochemical imbalance was recognized in carbohydrate, pentose phosphate, purine, pyrimidine, DNA, and polyamine metabolism and in other biochemical areas. Current work is directed to clarifying the enzymology and metabolic pattern of thymidine metabolism and CTP biosynthesis since these areas are of particular importance in selective chemotherapy and rescue. The activities of key enzymes in thymidine metabolism have been correlated with the growth rates in a spectrum of hepatomas. Increases in the activities of four key enzymes in CTP biosynthesis appear to be specific to neoplasia because no similar pattern was observed in the normal adult resting or regenerating liver or in the fetal and developing liver. The overall pattern discovered in transplantable rat hepatomas applies to other rodent tumors. It is of particular importance that the pattern of biochemical imbalance is also applicable to human hepatocellular carcinomas. With the recognition of the ordered pattern of reprogramming of gene expression in hepatomas, the path is open for the development of sensitive assays for biochemical diagnosis of liver tumors and for a rational design of selective chemotherapy and rescue."}
{"id": "PMID:224203", "title": "Limitations of current treatment methods for primary carcinoma of the liver.", "content": "Because the liver is the largest organ in the human body and is situated deep in a body cavity, large amounts of the parenchymal tissue can be replaced by malignant tissue before any symptoms are noticed. When clinical symptoms are present, the cancer has usually reached an advanced stage, severely limiting the useful application of current treatment methods for cure or prolonged palliation. At present, surgical resection may be expected to produce long-term survivors in 25% of patients resectable for cure. Improved tests for earlier diagnosis and increased awareness on the part of the physican and the patient are needed to permit diagnosis of this cancer in patients with stage I disease, which can be controlled for long periods of time.", "contents": "Limitations of current treatment methods for primary carcinoma of the liver. Because the liver is the largest organ in the human body and is situated deep in a body cavity, large amounts of the parenchymal tissue can be replaced by malignant tissue before any symptoms are noticed. When clinical symptoms are present, the cancer has usually reached an advanced stage, severely limiting the useful application of current treatment methods for cure or prolonged palliation. At present, surgical resection may be expected to produce long-term survivors in 25% of patients resectable for cure. Improved tests for earlier diagnosis and increased awareness on the part of the physican and the patient are needed to permit diagnosis of this cancer in patients with stage I disease, which can be controlled for long periods of time."}
{"id": "PMID:224204", "title": "Ultrastructure of hepatocellular tumors.", "content": "The lesions that appear during hepatocarcinogenesis can be separated into morphologically distinct entities, which have been arranged into sequences believed to represent stages in carcinogenesis. Similarly, the primary and transplantable hepato-cellular carcinomas (HCC) can be arranged into a sequence of stages believed to represent the progression toward the ultimate cancer cell. Separation of morphological entities has been most successful in rat liver. Ultrastructural studies differentiate between lesions derived from hepatocytes and those originating in other cellular components of the liver. They show that there is variability and divergence in the structure of cellular organelles in the early stages of carcinogenesis, that there is simplification of cellular structure and of organelles during the progression of HCC, and that qualitative changes specific for cancer cells do not exist. Toxic changes associated with the process of carcinogenesis are loss of stacks; wrapping of cisternae around mitochondria; dilation, denudation, and vesiculation of cisternae; increase of autophagy; depletion of glycogen, and enlargement of nuclei and nucleoli. Early changes are storage of glycogen and hyperplasia of smooth endoplasmic reticulum. Subsequent alterations are increased variability in the size, shape, and structure of mitochondria and in the structure of endoplasmic reticulum, including the appearance of fingerprints. A transient stage recognizable by storage of lipid may represent a degenerative process. Ultrastructural characteristics of basophilic cells such as abundance of free ribosomes and absence of glycogen and of smooth endoplasmic reticulum suggest that they may be a stage in the formation of HCC. Progression of HCC is associated with a decrease in the number and size of mitochondria, reduction of mitochondrial cristae, decrease in the number and complexity of microbodies, reduction of the tubulovesicular form of smooth reticulum, accumulation of free ribosomes, and increase of the granular component and condensation of the fibrillar component of nucleoli. Various types of nuclear inclusions reflect the increased mitotic rate of the neoplastic tissue. Changes of the cellular surface are believed to be associated with the ability of the cells to invade and metastasize. Future investigations will require the use of single doses of potent carcinogens, application of morphometric methods at the ultrastructural level, and acceptance of primates as models for human hepatocarcinogenesis.", "contents": "Ultrastructure of hepatocellular tumors. The lesions that appear during hepatocarcinogenesis can be separated into morphologically distinct entities, which have been arranged into sequences believed to represent stages in carcinogenesis. Similarly, the primary and transplantable hepato-cellular carcinomas (HCC) can be arranged into a sequence of stages believed to represent the progression toward the ultimate cancer cell. Separation of morphological entities has been most successful in rat liver. Ultrastructural studies differentiate between lesions derived from hepatocytes and those originating in other cellular components of the liver. They show that there is variability and divergence in the structure of cellular organelles in the early stages of carcinogenesis, that there is simplification of cellular structure and of organelles during the progression of HCC, and that qualitative changes specific for cancer cells do not exist. Toxic changes associated with the process of carcinogenesis are loss of stacks; wrapping of cisternae around mitochondria; dilation, denudation, and vesiculation of cisternae; increase of autophagy; depletion of glycogen, and enlargement of nuclei and nucleoli. Early changes are storage of glycogen and hyperplasia of smooth endoplasmic reticulum. Subsequent alterations are increased variability in the size, shape, and structure of mitochondria and in the structure of endoplasmic reticulum, including the appearance of fingerprints. A transient stage recognizable by storage of lipid may represent a degenerative process. Ultrastructural characteristics of basophilic cells such as abundance of free ribosomes and absence of glycogen and of smooth endoplasmic reticulum suggest that they may be a stage in the formation of HCC. Progression of HCC is associated with a decrease in the number and size of mitochondria, reduction of mitochondrial cristae, decrease in the number and complexity of microbodies, reduction of the tubulovesicular form of smooth reticulum, accumulation of free ribosomes, and increase of the granular component and condensation of the fibrillar component of nucleoli. Various types of nuclear inclusions reflect the increased mitotic rate of the neoplastic tissue. Changes of the cellular surface are believed to be associated with the ability of the cells to invade and metastasize. Future investigations will require the use of single doses of potent carcinogens, application of morphometric methods at the ultrastructural level, and acceptance of primates as models for human hepatocarcinogenesis."}
{"id": "PMID:224205", "title": "Histology and ultrastructural aspects of virus-induced primary liver cancer and transplantable hepatomas of viral origin in chickens.", "content": "The macroscopic, light microscopic and electron microscopic features and biological properties of MC-29 virus-induced hepatocellular carcinomas in chickens are described. The tumors developed in noncirrhotic livers within a very short time and formed metastases. Virus production was also evidenced in the tumors. There were also indications of virus production in the transplantable tumors. The tumors grew equally well after sc, ip, or im inoculation. In about 25% of the tumor-bearing animals, tumorous nodules developed in the liver. It could not be established whether they were metastases or primary liver cancers induced by viruses released from the transplantable tumors.", "contents": "Histology and ultrastructural aspects of virus-induced primary liver cancer and transplantable hepatomas of viral origin in chickens. The macroscopic, light microscopic and electron microscopic features and biological properties of MC-29 virus-induced hepatocellular carcinomas in chickens are described. The tumors developed in noncirrhotic livers within a very short time and formed metastases. Virus production was also evidenced in the tumors. There were also indications of virus production in the transplantable tumors. The tumors grew equally well after sc, ip, or im inoculation. In about 25% of the tumor-bearing animals, tumorous nodules developed in the liver. It could not be established whether they were metastases or primary liver cancers induced by viruses released from the transplantable tumors."}
{"id": "PMID:224210", "title": "Transformation-defective mutants of Rous sarcoma virus with longer sizes of genome RNA and their highly frequent occurrences.", "content": "Transformation-defective (td) mutants with different sizes of genomic RNA were isolated from the Prague strain of Rous sarcoma virus, subgroup C(PR-C). All six td viruses (tdTYPR-C) isolated from a single UV-irradiated stock of PR-C (clone 2 of TYPR-C) had slightly longer RNA than did the ordinary class b RNA of tdB77 and Rous-associated virus-7. td viruses spontaneously segregated in uncloned TYPR-C also contained genomic RNA of a size similar to tdTYPR-C RNA. On the other hand, two td mutants isolated from another stock of PR-C (LAPR-C) had the class b RNA. Fingerprint analysis confirmed that tdTYPR-C and tdLAPR-C were derived by deletion from clone 2 of TYPR-C and LAPR-C, respectively, and also showed that clone 2 of TYPR-C had sequences in its genome RNA different from those of LAPR-C, although it gave a fingerprinting pattern similar to the latter. These results strongly suggest that differences between the nucleotide sequences in TYPR-C and LAPR-C RNA may result in different extents of deletion.", "contents": "Transformation-defective mutants of Rous sarcoma virus with longer sizes of genome RNA and their highly frequent occurrences. Transformation-defective (td) mutants with different sizes of genomic RNA were isolated from the Prague strain of Rous sarcoma virus, subgroup C(PR-C). All six td viruses (tdTYPR-C) isolated from a single UV-irradiated stock of PR-C (clone 2 of TYPR-C) had slightly longer RNA than did the ordinary class b RNA of tdB77 and Rous-associated virus-7. td viruses spontaneously segregated in uncloned TYPR-C also contained genomic RNA of a size similar to tdTYPR-C RNA. On the other hand, two td mutants isolated from another stock of PR-C (LAPR-C) had the class b RNA. Fingerprint analysis confirmed that tdTYPR-C and tdLAPR-C were derived by deletion from clone 2 of TYPR-C and LAPR-C, respectively, and also showed that clone 2 of TYPR-C had sequences in its genome RNA different from those of LAPR-C, although it gave a fingerprinting pattern similar to the latter. These results strongly suggest that differences between the nucleotide sequences in TYPR-C and LAPR-C RNA may result in different extents of deletion."}
{"id": "PMID:224211", "title": "Translation of encephalomyocarditis virus RNA in reticulocyte lysates: kinetic analysis of the formation of virion proteins and a protein required for processing.", "content": "In cell-free extracts derived from rabbit reticulocytes, encephalomyocarditis RNA can be translated completely, and the products can be processed extensively to give encephalomyocarditis virion proteins and several nonvirion proteins, including a genome-coded protein required for processing. The latter is probably a protease. Translation is very efficient. Under typical conditions, each EMC RNA is translated approximately eight times during a 3-h period. Kinetic analyses (time-course experiments, pulse-chase experiments, and pulse-stop experiments) have been used to determine the time of appearance of major products, and these times have been correlated with map positions. The gene for the putative protease is located near the middle of the genome downstream from the virion protein genes. Ribosomes can travel the length of encephalomycarditis RNA within 30 min, but there is a delay in their progress along the RNA at some point soon after they traverse the region coding for virion protein precursors. This delay results in the accumulation of precursors for a period of about 10 min before the putative protease is made and virion proteins (epsilon, alpha, and gamma) are released by proteolysis.", "contents": "Translation of encephalomyocarditis virus RNA in reticulocyte lysates: kinetic analysis of the formation of virion proteins and a protein required for processing. In cell-free extracts derived from rabbit reticulocytes, encephalomyocarditis RNA can be translated completely, and the products can be processed extensively to give encephalomyocarditis virion proteins and several nonvirion proteins, including a genome-coded protein required for processing. The latter is probably a protease. Translation is very efficient. Under typical conditions, each EMC RNA is translated approximately eight times during a 3-h period. Kinetic analyses (time-course experiments, pulse-chase experiments, and pulse-stop experiments) have been used to determine the time of appearance of major products, and these times have been correlated with map positions. The gene for the putative protease is located near the middle of the genome downstream from the virion protein genes. Ribosomes can travel the length of encephalomycarditis RNA within 30 min, but there is a delay in their progress along the RNA at some point soon after they traverse the region coding for virion protein precursors. This delay results in the accumulation of precursors for a period of about 10 min before the putative protease is made and virion proteins (epsilon, alpha, and gamma) are released by proteolysis."}
{"id": "PMID:224206", "title": "Biochemical behavior of MC-29 virus-induced transplantable chicken hepatoma.", "content": "Studies were performed to test the applicability of the molecular correlation concept developed in chemically induced transplantable rat hepatomas to virally induced transplantable hepatoma in chicken. In a comparison of the activities of carbohydrate, purine, and pyrimidine key enzymes in rat and chicken hepatomas, similar patterns were observed in rodent and avian tumors. These results show that the enzymatic imbalance elucidated in chemically induced rat hepatomas is applicable to the virus-induced hepatoma in chicken, independent of the nature of the carcinogenic agent and the species.", "contents": "Biochemical behavior of MC-29 virus-induced transplantable chicken hepatoma. Studies were performed to test the applicability of the molecular correlation concept developed in chemically induced transplantable rat hepatomas to virally induced transplantable hepatoma in chicken. In a comparison of the activities of carbohydrate, purine, and pyrimidine key enzymes in rat and chicken hepatomas, similar patterns were observed in rodent and avian tumors. These results show that the enzymatic imbalance elucidated in chemically induced rat hepatomas is applicable to the virus-induced hepatoma in chicken, independent of the nature of the carcinogenic agent and the species."}
{"id": "PMID:224208", "title": "Comparative study of tumor-specific transplantation antigens of MC-29 chicken hepatoma and Rous sarcoma virus-induced sarcomas in mice.", "content": "Immunization of CBAT6T6 mice with MC-29 hepatoma antigen did not change the take of Rous sarcoma virus, Schmidt-Ruppin strain [RSV(SR)] mouse tumors after sc transplantation. Immunization with MC-29 hepatoma antigen only slightly increased the average survival time of the mice and significantly decreased tumor growth only at the minimal lethal dose level. Immunization of mice with MC-29 hepatoma antigen and immunization with chicken Rous sarcoma gave similar results; both elicited much less transplantation resistance than immunization with irradiated RSV(SR) mouse tumor cells. The data indicate that there are common tumor-specific transplantation antigens of MC-29 hepatoma and Rouse sarcoma, but further in vitro experiments are needed to prove this.", "contents": "Comparative study of tumor-specific transplantation antigens of MC-29 chicken hepatoma and Rous sarcoma virus-induced sarcomas in mice. Immunization of CBAT6T6 mice with MC-29 hepatoma antigen did not change the take of Rous sarcoma virus, Schmidt-Ruppin strain [RSV(SR)] mouse tumors after sc transplantation. Immunization with MC-29 hepatoma antigen only slightly increased the average survival time of the mice and significantly decreased tumor growth only at the minimal lethal dose level. Immunization of mice with MC-29 hepatoma antigen and immunization with chicken Rous sarcoma gave similar results; both elicited much less transplantation resistance than immunization with irradiated RSV(SR) mouse tumor cells. The data indicate that there are common tumor-specific transplantation antigens of MC-29 hepatoma and Rouse sarcoma, but further in vitro experiments are needed to prove this."}
{"id": "PMID:224212", "title": "Capsid protein precursor is one of two initiated products of translation of poliovirus RNA in vitro.", "content": "Previous studies in our laboratory have demonstrated that cell-free systems translating the Mahoney strain of poliovirus type I RNA utilize two unique initiation sites. In this study, defective-interfering particles of poliovirus, which contain deletions in the region encoding the capsid proteins, are shown to initiate translation of proteins in vitro at these same two sites. Both the standard virus and the defective-interfering virus RNA direct the synthesis of two polypeptides labeled with n-formyl-methionine (fmet) at their amino termini. The size of the smaller fmet polypeptide synthesized in vitro by the defective virus appears identical in size to that of the standard virus. However, the larger-molecular-weight fmet polypeptide is reduced in size from 115,000 to 69,000 daltons. This correlates exactly with the reduced size of the precursor to the capsid proteins synthesized by the defective virus in vivo and with the size of the deletion in the defective virus RNA (1,200 bases). This provides genetic evidence that the 115,000-dalton fmet polypeptide synthesized into vitro by the standard virus is NCVP1a, the precursor to the coat proteins. Although the identity of the small (5,000 to 10,000 daltons) fmet polypeptide is not clear, several lines of evidence enable us to exclude the possibility that it is VP4, the smallest viral capsid protein.", "contents": "Capsid protein precursor is one of two initiated products of translation of poliovirus RNA in vitro. Previous studies in our laboratory have demonstrated that cell-free systems translating the Mahoney strain of poliovirus type I RNA utilize two unique initiation sites. In this study, defective-interfering particles of poliovirus, which contain deletions in the region encoding the capsid proteins, are shown to initiate translation of proteins in vitro at these same two sites. Both the standard virus and the defective-interfering virus RNA direct the synthesis of two polypeptides labeled with n-formyl-methionine (fmet) at their amino termini. The size of the smaller fmet polypeptide synthesized in vitro by the defective virus appears identical in size to that of the standard virus. However, the larger-molecular-weight fmet polypeptide is reduced in size from 115,000 to 69,000 daltons. This correlates exactly with the reduced size of the precursor to the capsid proteins synthesized by the defective virus in vivo and with the size of the deletion in the defective virus RNA (1,200 bases). This provides genetic evidence that the 115,000-dalton fmet polypeptide synthesized into vitro by the standard virus is NCVP1a, the precursor to the coat proteins. Although the identity of the small (5,000 to 10,000 daltons) fmet polypeptide is not clear, several lines of evidence enable us to exclude the possibility that it is VP4, the smallest viral capsid protein."}
{"id": "PMID:224207", "title": "Chromatin alterations and gene function disorder in MC-29 virus-derived hepatoma.", "content": "The disorder of gene expression in hepatomas was studied by following certain metabolic alterations (enzyme stimulation, nucleic acid labeling) after glucocorticoid treatment and analyzing the site of action of glucocorticoids. Compared to normal liver, the MC-29 virus-derived transplantable hepatoma (VTH) responded abnormally to glucocorticoids, which failed to stimulate the activity of certain enzymes (glucose-6-phosphatase, aryl hydrocarbon hydroxylase) or to inhibit DNA synthesis. Since the binding capacity of the cytosol steroid receptor was the same in liver and VTH but the interaction between the steroid receptor and DNA was reduced in VTH, it was concluded that structural alterations of chromatin nonhistones--including processed steroid receptor--may be responsible for the lack of physiological responses to steroids in VTH. Furthermore, the increased proportion or repetitive sequences in VTH DNA may be a feature of the disorder of gene regulation in malignant cells.", "contents": "Chromatin alterations and gene function disorder in MC-29 virus-derived hepatoma. The disorder of gene expression in hepatomas was studied by following certain metabolic alterations (enzyme stimulation, nucleic acid labeling) after glucocorticoid treatment and analyzing the site of action of glucocorticoids. Compared to normal liver, the MC-29 virus-derived transplantable hepatoma (VTH) responded abnormally to glucocorticoids, which failed to stimulate the activity of certain enzymes (glucose-6-phosphatase, aryl hydrocarbon hydroxylase) or to inhibit DNA synthesis. Since the binding capacity of the cytosol steroid receptor was the same in liver and VTH but the interaction between the steroid receptor and DNA was reduced in VTH, it was concluded that structural alterations of chromatin nonhistones--including processed steroid receptor--may be responsible for the lack of physiological responses to steroids in VTH. Furthermore, the increased proportion or repetitive sequences in VTH DNA may be a feature of the disorder of gene regulation in malignant cells."}
{"id": "PMID:224209", "title": "Hepatocyte suspensions and cultures as tools in experimental carcinogenesis.", "content": "Isolation of preneoplastic cell populations would greatly facilitate analysis of the development of liver carcinogenesis. Suspensions of intact single cells can be prepared in an almost quantitative yield by two-step perfusion of the isolated liver. In the first step the liver is perfused with a Ca2+-free buffer (or with EGTA) in order to irreversibly cleave the desmosomes; in the second step perfusion with Ca2+-activated collagenase dissolves the collagenous extracellular matrix. The resulting single-cell suspension will be a mixture of intact normal and preneoplastic hepatocytes, other liver cell types (mostly Kupffer and endothelial cells), damaged cells, and subcellular debris. Intact hepatocytes can be purified--e.g., by differential centrifugation--but separation of preneoplastic from normal cells has not yet been achieved. Density gradient separation or selection in culture on the basis of the unique properties of preneoplastic hepatocytes (e.g., drug resistance) may prove useful. The use of hepatocyte cultures and liver-derived epithelial cell lines as test systems and models for chemical carcinogenesis in vitro is briefly reviewed.", "contents": "Hepatocyte suspensions and cultures as tools in experimental carcinogenesis. Isolation of preneoplastic cell populations would greatly facilitate analysis of the development of liver carcinogenesis. Suspensions of intact single cells can be prepared in an almost quantitative yield by two-step perfusion of the isolated liver. In the first step the liver is perfused with a Ca2+-free buffer (or with EGTA) in order to irreversibly cleave the desmosomes; in the second step perfusion with Ca2+-activated collagenase dissolves the collagenous extracellular matrix. The resulting single-cell suspension will be a mixture of intact normal and preneoplastic hepatocytes, other liver cell types (mostly Kupffer and endothelial cells), damaged cells, and subcellular debris. Intact hepatocytes can be purified--e.g., by differential centrifugation--but separation of preneoplastic from normal cells has not yet been achieved. Density gradient separation or selection in culture on the basis of the unique properties of preneoplastic hepatocytes (e.g., drug resistance) may prove useful. The use of hepatocyte cultures and liver-derived epithelial cell lines as test systems and models for chemical carcinogenesis in vitro is briefly reviewed."}
{"id": "PMID:224213", "title": "Protein synthesized early after infection is linked to the termini of adenovirus type 2 DNA synthesized in vivo and in vitro.", "content": "The human adenovirus DNA genome contains a protein (CBP, or covalently bound protein) linked to each 5' terminus. To assess whether CBP is synthesized early, infected cells were incubated with hydroxyurea from 1 to 18 h postinfection, the hydroxyurea was removed, cycloheximide was added, and viral DNA was labeled with [3H]thymidine from 18 to 23 h postinfection. Removal of hydroxyurea at 18 h postinfection permits the synthesis of viral DNA, whereas cycloheximide maintains the block in late viral protein synthesis. Three lines of evidence are presented to show that viral 3H-labeled DNA prepared by this procedure was linked to CBP: (I) the DNA sedimented more rapidly than protein-free DNA (i.e., protinase treated) in neutral sucrose gradients containing guanidine  hydrochloride; (ii) the DNA banded at a lower density than protein-free DNA in CsCl gradients containing guanidine hydrochloride; and (iii) neither the 3H-labeled DNA nor the end fragments produced by EcoRI digestion entered a 1.4% agarose gel during electrophoresis. These experiments are strong evidence that CBP is not a product of a late viral gene and is therefore the product of either an early viral gene or a cell gene. Experiments were performed to test whether CBP is attached to viral DNA synthesized in vitro by a soluble complex that synthesizes exclusively viral DNA as completed viral genomes in vitro. In vitro-labeled DNA was analyzed by velocity sedimentation, equilibrium sedimentation, and agarose gel electrophoresis as described above. Our results indicate that the majority of in vitro-synthesized DNA molecules were attached to CBP. These results, which indicate that CBP is synthesized early after infection and is attached to viral DNA labeled in vitro by a soluble replication complex, are consistent with the idea that CBP may play a role in viral DNA replication.", "contents": "Protein synthesized early after infection is linked to the termini of adenovirus type 2 DNA synthesized in vivo and in vitro. The human adenovirus DNA genome contains a protein (CBP, or covalently bound protein) linked to each 5' terminus. To assess whether CBP is synthesized early, infected cells were incubated with hydroxyurea from 1 to 18 h postinfection, the hydroxyurea was removed, cycloheximide was added, and viral DNA was labeled with [3H]thymidine from 18 to 23 h postinfection. Removal of hydroxyurea at 18 h postinfection permits the synthesis of viral DNA, whereas cycloheximide maintains the block in late viral protein synthesis. Three lines of evidence are presented to show that viral 3H-labeled DNA prepared by this procedure was linked to CBP: (I) the DNA sedimented more rapidly than protein-free DNA (i.e., protinase treated) in neutral sucrose gradients containing guanidine  hydrochloride; (ii) the DNA banded at a lower density than protein-free DNA in CsCl gradients containing guanidine hydrochloride; and (iii) neither the 3H-labeled DNA nor the end fragments produced by EcoRI digestion entered a 1.4% agarose gel during electrophoresis. These experiments are strong evidence that CBP is not a product of a late viral gene and is therefore the product of either an early viral gene or a cell gene. Experiments were performed to test whether CBP is attached to viral DNA synthesized in vitro by a soluble complex that synthesizes exclusively viral DNA as completed viral genomes in vitro. In vitro-labeled DNA was analyzed by velocity sedimentation, equilibrium sedimentation, and agarose gel electrophoresis as described above. Our results indicate that the majority of in vitro-synthesized DNA molecules were attached to CBP. These results, which indicate that CBP is synthesized early after infection and is attached to viral DNA labeled in vitro by a soluble replication complex, are consistent with the idea that CBP may play a role in viral DNA replication."}
{"id": "PMID:224214", "title": "Polyoma viruses with mutations at endonuclease HindII site 1: alterations at the COOH terminus of VP1.", "content": "Four mutants of polyoma virus lacking endonuclease HindII site 1 were isolated and characterized with respect to the VP1 coding sequence. Three of these mutants had deletions that removed 0.2 to 0.3% of the genome. All three deletion mutants encoded VP1 proteins that were smaller than wild type and that lacked one or more tryptic peptides normally found in the wild-type VP1 protein. Our results suggest the HindII site 1 is at, or very near, the carboxy terminal end of the coding sequence for VP1. A model for the peptide organization in that region is presented.", "contents": "Polyoma viruses with mutations at endonuclease HindII site 1: alterations at the COOH terminus of VP1. Four mutants of polyoma virus lacking endonuclease HindII site 1 were isolated and characterized with respect to the VP1 coding sequence. Three of these mutants had deletions that removed 0.2 to 0.3% of the genome. All three deletion mutants encoded VP1 proteins that were smaller than wild type and that lacked one or more tryptic peptides normally found in the wild-type VP1 protein. Our results suggest the HindII site 1 is at, or very near, the carboxy terminal end of the coding sequence for VP1. A model for the peptide organization in that region is presented."}
{"id": "PMID:224215", "title": "Subcellular Localization of simian virus 40 large tumor antigen.", "content": "The distribution of simian virus 40 large tumor antigen in subcellular fractions from simian virus 40-transformed hamster (H-50) and mouse (VLM) cells and from simian virus 40-infected monkey cells was determined. Solubilized [(35)S]-methionine- or (32)P(i)-labeled surface membrane and nuclear fractions were prepared, immunoprecipitated with hamster anti-T serum, and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Tumor antigen with an apparent molecular weight of approximately 96,000 was detected in both subcellular fractions. Minor components of approximately 68,000 and approximately 56,000 with anti-T reactivity which labeled with [(35)S]methionine were also detected in both fractions from H-50 cells, as were components of approximately 140,000 and approximately 56,000 from VLM cells. The 56,000 component appeared to be greatly reduced in (32)P(i)-labeled surface membrane fractions. Normal cells or cells transformed with a heterologous agent, such as polyoma virus or a chemical carcinogen, lacked immunoprecipitable tumor antigen. Cell fractionation was monitored by [(3)H]thymidine labeling, NADH-diaphorase activity, and Na(+)-K(+)-dependent ATPase activity. These analyses revealed only trace contamination of surface membranes by nuclei, extremely low levels of nuclear rupture during homogenization, and an approximate 10-fold enrichment of surface membrane. Reconstruction experiments demonstrated that soluble tumor antigen failed to associate or copurify with surface membranes during fractionation procedures. These results indicate the presence of a protein in the plasma membrane of cells transformed or infected by simian virus 40 that is immunologically indistinguishable from nuclear tumor antigen.", "contents": "Subcellular Localization of simian virus 40 large tumor antigen. The distribution of simian virus 40 large tumor antigen in subcellular fractions from simian virus 40-transformed hamster (H-50) and mouse (VLM) cells and from simian virus 40-infected monkey cells was determined. Solubilized [(35)S]-methionine- or (32)P(i)-labeled surface membrane and nuclear fractions were prepared, immunoprecipitated with hamster anti-T serum, and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Tumor antigen with an apparent molecular weight of approximately 96,000 was detected in both subcellular fractions. Minor components of approximately 68,000 and approximately 56,000 with anti-T reactivity which labeled with [(35)S]methionine were also detected in both fractions from H-50 cells, as were components of approximately 140,000 and approximately 56,000 from VLM cells. The 56,000 component appeared to be greatly reduced in (32)P(i)-labeled surface membrane fractions. Normal cells or cells transformed with a heterologous agent, such as polyoma virus or a chemical carcinogen, lacked immunoprecipitable tumor antigen. Cell fractionation was monitored by [(3)H]thymidine labeling, NADH-diaphorase activity, and Na(+)-K(+)-dependent ATPase activity. These analyses revealed only trace contamination of surface membranes by nuclei, extremely low levels of nuclear rupture during homogenization, and an approximate 10-fold enrichment of surface membrane. Reconstruction experiments demonstrated that soluble tumor antigen failed to associate or copurify with surface membranes during fractionation procedures. These results indicate the presence of a protein in the plasma membrane of cells transformed or infected by simian virus 40 that is immunologically indistinguishable from nuclear tumor antigen."}
{"id": "PMID:224216", "title": "Structural analysis of the intracellular RNAs of murine mammary tumor virus.", "content": "We have characterized murine mammary tumor virus (MuMTV)-specific RNA in several types of cells in which viral DNA is transcribed into RNA: cultured GR mouse mammary tumor cells, S49 lymphoma cells from BALB/c mice, lactating mammary glands from C57BL/6 mice, and mink lung cells infected in vitro with MuMTV. In all cell types studied, there are three distinct species of intracellular viral RNA, with sedimentation coefficients of 35S, 24S, and 13S (or molecular weights of 3.1 X 10(6), 1.5 X 10(6), and 0.37 X 10(6), as determined by rate-zonal sedimentation in sucrose gradients and by electrophoresis in agarose gels under denaturing conditions. These three viral RNA species appear to be present regardless of viral RNA concentration, responsiveness to glucocorticoid hormones, production of extracellular virus, and use of either endogenous or acquired MuMTV proviral DNA as template. The three viral RNAs display characteristics of mRNAs in that they are polyadenylated, associated with polyribosomes, and released from polyribosomes by treatment with EDTA; hence all three species presumably direct the synthesis of virus-coded proteins. The two larger species of viral RNA are probably responsible for synthesis of the structural proteins of the virion, but the function of the 13S RNA is not known. Both of the subgenomic RNAs contain sequences found at the 3' terminus of 35S (or genomic) RNA. However, only the 24S RNA (not the 13S RNA) contains sequences which are located at the 5' terminus of 35S RNA and are apparently transposed during RNA synthesis of maturation, as described for subgenomic mRNA's of other retroviruses.", "contents": "Structural analysis of the intracellular RNAs of murine mammary tumor virus. We have characterized murine mammary tumor virus (MuMTV)-specific RNA in several types of cells in which viral DNA is transcribed into RNA: cultured GR mouse mammary tumor cells, S49 lymphoma cells from BALB/c mice, lactating mammary glands from C57BL/6 mice, and mink lung cells infected in vitro with MuMTV. In all cell types studied, there are three distinct species of intracellular viral RNA, with sedimentation coefficients of 35S, 24S, and 13S (or molecular weights of 3.1 X 10(6), 1.5 X 10(6), and 0.37 X 10(6), as determined by rate-zonal sedimentation in sucrose gradients and by electrophoresis in agarose gels under denaturing conditions. These three viral RNA species appear to be present regardless of viral RNA concentration, responsiveness to glucocorticoid hormones, production of extracellular virus, and use of either endogenous or acquired MuMTV proviral DNA as template. The three viral RNAs display characteristics of mRNAs in that they are polyadenylated, associated with polyribosomes, and released from polyribosomes by treatment with EDTA; hence all three species presumably direct the synthesis of virus-coded proteins. The two larger species of viral RNA are probably responsible for synthesis of the structural proteins of the virion, but the function of the 13S RNA is not known. Both of the subgenomic RNAs contain sequences found at the 3' terminus of 35S (or genomic) RNA. However, only the 24S RNA (not the 13S RNA) contains sequences which are located at the 5' terminus of 35S RNA and are apparently transposed during RNA synthesis of maturation, as described for subgenomic mRNA's of other retroviruses."}
{"id": "PMID:224217", "title": "Simian virus 40 gene A regulation of cellular DNA synthesis. I. In permissive cells.", "content": "The kinetics of host cellular DNA stimulation by simian virus 40 (SV40) tsA58 infection was studied by flow microfluorometry and autoradiography in two types of productively infected monkey kidney cells (AGMK, secondary passage, and the TC-7 cell line). Prior to infection, the cell populations were maintained predominantly in G0-G1 hase of the cell cycle by low (0.25%) serum concentration. Infection of TC-7 or AGMK cells by wild-type SV40, viable deletion mutant dl890, or by SV40 tsA58 at 33 degrees C induced cells through S phase after which they were blocked with a 4N DNA content in the G2 phase. The infection of TC-7 cells by tsA58 at 41 degrees C, which was a nonpermissive temperature for viral DNA replication, induced a round of cell DNA synthesis in approximately 30% of the cell population. These cells proceeded through S phase but then re-entered the G1 resting state. In contrast, infection of AGMK cells by tsA58 at 41 degrees C induced DNA synthesis in approximately 50% of the cells, but this population remained blocked in the G2 phase. These results indicate that the mitogenic effect of the A gene product upon cellular DNA is more heat resistant than its regulating activity on viral DNA synthesis and that the extent of induction of cell DNA synthesis by the A gene product may be influenced by the host cell.", "contents": "Simian virus 40 gene A regulation of cellular DNA synthesis. I. In permissive cells. The kinetics of host cellular DNA stimulation by simian virus 40 (SV40) tsA58 infection was studied by flow microfluorometry and autoradiography in two types of productively infected monkey kidney cells (AGMK, secondary passage, and the TC-7 cell line). Prior to infection, the cell populations were maintained predominantly in G0-G1 hase of the cell cycle by low (0.25%) serum concentration. Infection of TC-7 or AGMK cells by wild-type SV40, viable deletion mutant dl890, or by SV40 tsA58 at 33 degrees C induced cells through S phase after which they were blocked with a 4N DNA content in the G2 phase. The infection of TC-7 cells by tsA58 at 41 degrees C, which was a nonpermissive temperature for viral DNA replication, induced a round of cell DNA synthesis in approximately 30% of the cell population. These cells proceeded through S phase but then re-entered the G1 resting state. In contrast, infection of AGMK cells by tsA58 at 41 degrees C induced DNA synthesis in approximately 50% of the cells, but this population remained blocked in the G2 phase. These results indicate that the mitogenic effect of the A gene product upon cellular DNA is more heat resistant than its regulating activity on viral DNA synthesis and that the extent of induction of cell DNA synthesis by the A gene product may be influenced by the host cell."}
{"id": "PMID:224218", "title": "Late replicative intermediates are accumulated during simian virus 40 DNA replication in vivo and in vitro.", "content": "Simian virus 40 (SV40) replicating chromosomes were extracted from nuclei of infected cells. The chromosomes in the extract were resolved on neutral sucrose gradients, and the extent of replication of the DNA in the chromosome peaks was determined. The extract, in combination with cytosol factors and the appropriate  precursors, supports the continued replication of viral DNA. The products of the incubation were mature form I DNA and molecules (after deproteinization) with sedimentation coefficients, in neutral sucrose, of 22S and 29S. The results of our analysis of this system indicate the following. (i) The 22S molecule, which has been described by previous workers, is a relaxed, replicating molecule and is an artifact of the in vitro system. (ii) When the in vitro synthesis is performed at optimal ionic strength (150 mM potassium acetate), the artifactual 22S molecule does not appear. (iii) Late replicative intermediates do accumulate in vivo and in vitro. The major late form accumulated is 91% completed. (iv) The replicating chromosomes can be resolved into two distinct peaks on neutral sucrose gradients. The molecules in these peaks differ in extent of replication. (v) The nuclear extraction procedure preferentially extracts early replicating chromosomes. The relevance of these data to the problem of SV40 and cellular chromosome replication and termination is described.", "contents": "Late replicative intermediates are accumulated during simian virus 40 DNA replication in vivo and in vitro. Simian virus 40 (SV40) replicating chromosomes were extracted from nuclei of infected cells. The chromosomes in the extract were resolved on neutral sucrose gradients, and the extent of replication of the DNA in the chromosome peaks was determined. The extract, in combination with cytosol factors and the appropriate  precursors, supports the continued replication of viral DNA. The products of the incubation were mature form I DNA and molecules (after deproteinization) with sedimentation coefficients, in neutral sucrose, of 22S and 29S. The results of our analysis of this system indicate the following. (i) The 22S molecule, which has been described by previous workers, is a relaxed, replicating molecule and is an artifact of the in vitro system. (ii) When the in vitro synthesis is performed at optimal ionic strength (150 mM potassium acetate), the artifactual 22S molecule does not appear. (iii) Late replicative intermediates do accumulate in vivo and in vitro. The major late form accumulated is 91% completed. (iv) The replicating chromosomes can be resolved into two distinct peaks on neutral sucrose gradients. The molecules in these peaks differ in extent of replication. (v) The nuclear extraction procedure preferentially extracts early replicating chromosomes. The relevance of these data to the problem of SV40 and cellular chromosome replication and termination is described."}
{"id": "PMID:224219", "title": "Evolutionary relationships of the primate papovaviruses: base sequence homology among the genomes of simian virus 40, stump-tailed macaque virus, and SA12 virus.", "content": "Physical maps of the genomes of the two newly discovered primate papovaviruses, SA12 and stump-tailed macaque virus (STMV), were generated by restriction endonuclease analysis. The base sequence homologies among the genomes of SA12, stump-tailed macaque virus, and simian virus 40 (SV40) were studied by heteroduplex analysis. Heteroduplexes between SA12 and SV40 DNAs and stump-tailed macaque virus and SV40 DNAs were constructed and mounted for electron microscopy in various amounts of formamide to achieve a range of effective temperatures. At each effective temperature, the regions of duplex DNA in the heteroduplexes were measured and localized on the SV40 physical and functional maps. By analyzing the data from this study and rom our previous study (N. Newell, C. J. Lai, G. Khoury, and T. J. Kelly Jr., J. Virol. 25:193-201, 1978) on the base sequence homology between the genomes of BK virus and SV40, some general conclusions have been drawn concerning the evolutionary relationships among the genomes of the primate papovaviruses. The extent of homology among the viral genomes does not reflect the phylogenetic relationships of their hosts. At comparable effective temperatures Tm - 33 degrees C), the heteroduplexes between the DNAs of BK virus and SV40 contained the largest amount of duplex (about 90%). The heteroduplexes made between SA12 and SV40 DNAs were slightly less homologous, containing about 80% duplex. The heteroduplexes made between SV40 and stump-tailed macaque virus DNAs were only 20% duplex under the same conditions. When the various heteroduplexes were mounted for microscopy at effective temperatures greater than Tm - 33 degrees C, the fraction of the duplex DNA decreased in each case, indicating the existence of considerable base mismatching in the homologous regions. When specific coding or noncoding regions of the viral genomes were compared, the data indicated that the extent of sequence divergence differed markedly from one region to another. In all the heteroduplexes studied, there were two regions, located near the junctions between early and late regions on the SV40 map, which were essentially nonhomologous. All of the heteroduplexes studied showed significantly greater homology in the late region than in early region. Within the late region, the sequences coding for the major capsid polypeptide, VP1, were the most highly conserved.", "contents": "Evolutionary relationships of the primate papovaviruses: base sequence homology among the genomes of simian virus 40, stump-tailed macaque virus, and SA12 virus. Physical maps of the genomes of the two newly discovered primate papovaviruses, SA12 and stump-tailed macaque virus (STMV), were generated by restriction endonuclease analysis. The base sequence homologies among the genomes of SA12, stump-tailed macaque virus, and simian virus 40 (SV40) were studied by heteroduplex analysis. Heteroduplexes between SA12 and SV40 DNAs and stump-tailed macaque virus and SV40 DNAs were constructed and mounted for electron microscopy in various amounts of formamide to achieve a range of effective temperatures. At each effective temperature, the regions of duplex DNA in the heteroduplexes were measured and localized on the SV40 physical and functional maps. By analyzing the data from this study and rom our previous study (N. Newell, C. J. Lai, G. Khoury, and T. J. Kelly Jr., J. Virol. 25:193-201, 1978) on the base sequence homology between the genomes of BK virus and SV40, some general conclusions have been drawn concerning the evolutionary relationships among the genomes of the primate papovaviruses. The extent of homology among the viral genomes does not reflect the phylogenetic relationships of their hosts. At comparable effective temperatures Tm - 33 degrees C), the heteroduplexes between the DNAs of BK virus and SV40 contained the largest amount of duplex (about 90%). The heteroduplexes made between SA12 and SV40 DNAs were slightly less homologous, containing about 80% duplex. The heteroduplexes made between SV40 and stump-tailed macaque virus DNAs were only 20% duplex under the same conditions. When the various heteroduplexes were mounted for microscopy at effective temperatures greater than Tm - 33 degrees C, the fraction of the duplex DNA decreased in each case, indicating the existence of considerable base mismatching in the homologous regions. When specific coding or noncoding regions of the viral genomes were compared, the data indicated that the extent of sequence divergence differed markedly from one region to another. In all the heteroduplexes studied, there were two regions, located near the junctions between early and late regions on the SV40 map, which were essentially nonhomologous. All of the heteroduplexes studied showed significantly greater homology in the late region than in early region. Within the late region, the sequences coding for the major capsid polypeptide, VP1, were the most highly conserved."}
{"id": "PMID:224220", "title": "Detection of virus-specific RNA in simian sarcoma-leukemia virus-infected cells in in situ hybridization to viral complementary DNA.", "content": "An in situ molecular hybridization system which will detect retrovirus RNA in the cytoplasm of individual virus-infected cells has been developed. The technique was applied to cells infected with simian sarcoma-leukemia virus, where the virus-specific RNA was detected by hybridization to simian sarcoma-leukemia virus 3H-labeled complementary DNA. The system is useful for detecting viral RNA-containing cells in the presence of an excess of virus-negative cells and for determining which type of cell in a heterogenous population is  expressing viral RNA.", "contents": "Detection of virus-specific RNA in simian sarcoma-leukemia virus-infected cells in in situ hybridization to viral complementary DNA. An in situ molecular hybridization system which will detect retrovirus RNA in the cytoplasm of individual virus-infected cells has been developed. The technique was applied to cells infected with simian sarcoma-leukemia virus, where the virus-specific RNA was detected by hybridization to simian sarcoma-leukemia virus 3H-labeled complementary DNA. The system is useful for detecting viral RNA-containing cells in the presence of an excess of virus-negative cells and for determining which type of cell in a heterogenous population is  expressing viral RNA."}
{"id": "PMID:224222", "title": "Clinical features of acute coxsackie B viral myocarditis.", "content": "Clinical features of 11 patients of acute Coxsackie B viral myocarditis diagnosed by neutralizing antibody titers were reported. All patients had a flu-like symptom and 8 patients had fever. Initial cardiac manifestations were congestive heart failure in 9 patients, and syncopal attack in 4 patients. Electrocardiographic abnormalities frequently observed were non-specific ST-T changes, low voltage, and intraventricular conduction, disturbances including 4 patients of complete A-V block due to trifascicular block. Ten patients had a rise of serum enzymes. It seemed that in severe patients the serum enzymes rose markedly. From the analysis of laboratory and histological findings. Coxsackie B viral myocarditis were often complicated by hepatitis.", "contents": "Clinical features of acute coxsackie B viral myocarditis. Clinical features of 11 patients of acute Coxsackie B viral myocarditis diagnosed by neutralizing antibody titers were reported. All patients had a flu-like symptom and 8 patients had fever. Initial cardiac manifestations were congestive heart failure in 9 patients, and syncopal attack in 4 patients. Electrocardiographic abnormalities frequently observed were non-specific ST-T changes, low voltage, and intraventricular conduction, disturbances including 4 patients of complete A-V block due to trifascicular block. Ten patients had a rise of serum enzymes. It seemed that in severe patients the serum enzymes rose markedly. From the analysis of laboratory and histological findings. Coxsackie B viral myocarditis were often complicated by hepatitis."}
{"id": "PMID:224228", "title": "Clostridium perfringens exotoxins. VI. Reactivity of perfringolysin O with thiol and disulfide compounds.", "content": "The reactivity of perfringolysin O with thiol and disulfide compounds was studied. The activation potency of thiols was roughly proportional to the reaction rate constants of 5,5'-dithiobis-(2-nitrobenzoic acid) with thiols, which should be inversely proportional to their oxidation-reduction potentials. 1,2-Dimercaptoethane, which had the highest rate constant, most potently activated the toxin among the thiols tested and 4,4'-dipyridyl disulfide, which is known to be one of the most potent thiol-disulfide exchanging reagents, strongly inhibited toxin activity. Toxin activity was also inhibited by other thiol inhibitors.", "contents": "Clostridium perfringens exotoxins. VI. Reactivity of perfringolysin O with thiol and disulfide compounds. The reactivity of perfringolysin O with thiol and disulfide compounds was studied. The activation potency of thiols was roughly proportional to the reaction rate constants of 5,5'-dithiobis-(2-nitrobenzoic acid) with thiols, which should be inversely proportional to their oxidation-reduction potentials. 1,2-Dimercaptoethane, which had the highest rate constant, most potently activated the toxin among the thiols tested and 4,4'-dipyridyl disulfide, which is known to be one of the most potent thiol-disulfide exchanging reagents, strongly inhibited toxin activity. Toxin activity was also inhibited by other thiol inhibitors."}
{"id": "PMID:224229", "title": "Pathology of diarrhea due to mouse hepatitis virus in the infant mouse.", "content": "Two-day-old mice were inoculated orally with a mouse hepatitis virus which had been isolated from a suckling mouse with fatal diarrhea, and a systemic infection was shown to be established, though enterotropism of the isolate was evident. Significant viral growth and syncytium forming lesions were first detectable in the intestines at day 2 postinoculation, followed by the development of focal necrotic hepatitis. The virus titer in both liver and intestine attained maximum levels at days 4 to 5. Death occurred at day 5 or later, and 60 to 100% mice died during the first 2 weeks of life. Before death, some mice showed neurologic signs with high titered viruses recovered from the brain. The necrotizing lesions were also demonstrated in the lung and lymphoid organs.", "contents": "Pathology of diarrhea due to mouse hepatitis virus in the infant mouse. Two-day-old mice were inoculated orally with a mouse hepatitis virus which had been isolated from a suckling mouse with fatal diarrhea, and a systemic infection was shown to be established, though enterotropism of the isolate was evident. Significant viral growth and syncytium forming lesions were first detectable in the intestines at day 2 postinoculation, followed by the development of focal necrotic hepatitis. The virus titer in both liver and intestine attained maximum levels at days 4 to 5. Death occurred at day 5 or later, and 60 to 100% mice died during the first 2 weeks of life. Before death, some mice showed neurologic signs with high titered viruses recovered from the brain. The necrotizing lesions were also demonstrated in the lung and lymphoid organs."}
{"id": "PMID:224231", "title": "Continuous lines of RSV-transformed embryo cells and peritoneal macrophages of Japanese quails.", "content": "Four continuous lines of RSV-transformed quail cells were established; QERC-31F and QERC-31N cells derived from quail embryo cells and PERP and PERY cells from adult quail peritoneal macrophages. Marked morphological difference was noted between QERC-31F and QERC-31N; the former showed fusiform shape and the latter nodular shape. Both PERP and PERY showed macrophage-like morphology with phagocytic capacity. All four cell lines contained gs antigen and gp 85. Production of transforming virus was found in QERC-31N, PERP and PERY. In spite of failure in production of transforming virus, EQRC-31F was demonstrated to produce C-type particles by electron microscopy and to contain tumor-specific surface antigen by in vivo immunization and in vitro microcytotoxicity tests.", "contents": "Continuous lines of RSV-transformed embryo cells and peritoneal macrophages of Japanese quails. Four continuous lines of RSV-transformed quail cells were established; QERC-31F and QERC-31N cells derived from quail embryo cells and PERP and PERY cells from adult quail peritoneal macrophages. Marked morphological difference was noted between QERC-31F and QERC-31N; the former showed fusiform shape and the latter nodular shape. Both PERP and PERY showed macrophage-like morphology with phagocytic capacity. All four cell lines contained gs antigen and gp 85. Production of transforming virus was found in QERC-31N, PERP and PERY. In spite of failure in production of transforming virus, EQRC-31F was demonstrated to produce C-type particles by electron microscopy and to contain tumor-specific surface antigen by in vivo immunization and in vitro microcytotoxicity tests."}
{"id": "PMID:224232", "title": "Histopathological factors predictive for prognosis of lung cancer.", "content": "This study was done on 110 lung cancer patients who had received surgical resection consisted of two groups; one group of 43 who survived more than 5 years without recurrence and the other group of 67 who died within one year following surgery. Prognostic significance of the histopathological features at the primary tumor site as well as the regional lymph nodes were compared between the two groups. Blood vessel invasion by the tumor and lymph node metastasis appeared to be equally significant prognostic factors. Patients having the both factors had little chance for survival. Abundant lymphoid cell infiltration around the tumor was associated with longer survival. Lymphoid cell infiltration at the site of blood vessel invasion also was associated with better prognosis. Follicular hyperplasia and paracortical hyperplasia in the regional lymph nodes were favorable prognostic indicators, whereas sinus histocytosis was poorly significant prognostic indicator.", "contents": "Histopathological factors predictive for prognosis of lung cancer. This study was done on 110 lung cancer patients who had received surgical resection consisted of two groups; one group of 43 who survived more than 5 years without recurrence and the other group of 67 who died within one year following surgery. Prognostic significance of the histopathological features at the primary tumor site as well as the regional lymph nodes were compared between the two groups. Blood vessel invasion by the tumor and lymph node metastasis appeared to be equally significant prognostic factors. Patients having the both factors had little chance for survival. Abundant lymphoid cell infiltration around the tumor was associated with longer survival. Lymphoid cell infiltration at the site of blood vessel invasion also was associated with better prognosis. Follicular hyperplasia and paracortical hyperplasia in the regional lymph nodes were favorable prognostic indicators, whereas sinus histocytosis was poorly significant prognostic indicator."}
{"id": "PMID:224234", "title": "Assessment of host immune status during progressive growth and after excision of DNA virus (simian virus 40) tumors in hamsters: comparison of tumor-specific and tumor-unrelated parameters of immune responsiveness.", "content": "The kinetics of cell-mediated immunity to simian virus 40 (SV40) tumor-specific transplantation antigen (TSTA) were compared to the kinetics of tumor-unrelated parameters of immune responsiveness in the assessment of the immune statuses of inbred MHA/SsLAK hamsters during the course of progressive syngeneic SV40 tumor growth and after tumor excision. With the use of the tumor cell neutralization test in vivo and the macrophage migration inhibition assay in vitro, specific cellular immunity to SV40 TSTA was detected by 4 days after tumor cell inoculation, when the tumor was small. This tumor-specific immune response was no longer detected at 7 days after tumor cell inoculation, when the tumor had reached a mean diameter of 12.5 mm, but it returned by 14 days after surgical excision of the tumor. The patterns of host responsiveness to mitogens in spleen cells derived from tumor-bearing animals or from tumor-excised animals generally showed little or no correlation with the kinetics of tumor-specific cellular immunity. The kinetics of the humoral immune response to murine erythrocytes, as determined by hemagglutination assays, correlated much more closely with the kinetics of tumor-specific immunity than did the responses to mitogens. IgG antibody (T-dependent) responses were more affected by progressive tumor growth than were IgM antibody (T-independent) responses. The data suggest that results of tests with the use of tumor-unrelated parameters of immune responsiveness for the assessment of the immune status of cancer patients should be interpreted with caution.", "contents": "Assessment of host immune status during progressive growth and after excision of DNA virus (simian virus 40) tumors in hamsters: comparison of tumor-specific and tumor-unrelated parameters of immune responsiveness. The kinetics of cell-mediated immunity to simian virus 40 (SV40) tumor-specific transplantation antigen (TSTA) were compared to the kinetics of tumor-unrelated parameters of immune responsiveness in the assessment of the immune statuses of inbred MHA/SsLAK hamsters during the course of progressive syngeneic SV40 tumor growth and after tumor excision. With the use of the tumor cell neutralization test in vivo and the macrophage migration inhibition assay in vitro, specific cellular immunity to SV40 TSTA was detected by 4 days after tumor cell inoculation, when the tumor was small. This tumor-specific immune response was no longer detected at 7 days after tumor cell inoculation, when the tumor had reached a mean diameter of 12.5 mm, but it returned by 14 days after surgical excision of the tumor. The patterns of host responsiveness to mitogens in spleen cells derived from tumor-bearing animals or from tumor-excised animals generally showed little or no correlation with the kinetics of tumor-specific cellular immunity. The kinetics of the humoral immune response to murine erythrocytes, as determined by hemagglutination assays, correlated much more closely with the kinetics of tumor-specific immunity than did the responses to mitogens. IgG antibody (T-dependent) responses were more affected by progressive tumor growth than were IgM antibody (T-independent) responses. The data suggest that results of tests with the use of tumor-unrelated parameters of immune responsiveness for the assessment of the immune status of cancer patients should be interpreted with caution."}
{"id": "PMID:224235", "title": "Association of tumor induction by ultraviolet light-inactivated adenovirus 2-simian virus 40 recombinants with a specific segment of simian virus 40 DNA.", "content": "The nondefective (ND) adenovirus 2 (Ad2)-simian virus 40 (SV40) hybrid Ad2+ND4, which contains the segment of the SV40 genome between map positions 0.11 and 0.59, induced tumors in Syrian golden hamsters after inactivation by UV light. Ad2 and the Ad2+ND2 hybrid, which contains the segment of the SV40 genome between map positions 0.11 and 0.43, were not oncogenic after inactivation by UV light. These results showed that the incorporation of a specific segment of SV40 DNA into the Ad2 genome can alter the pathogenesis of the Ad2+ND4 virus by rendering it oncogenic for hamsters.", "contents": "Association of tumor induction by ultraviolet light-inactivated adenovirus 2-simian virus 40 recombinants with a specific segment of simian virus 40 DNA. The nondefective (ND) adenovirus 2 (Ad2)-simian virus 40 (SV40) hybrid Ad2+ND4, which contains the segment of the SV40 genome between map positions 0.11 and 0.59, induced tumors in Syrian golden hamsters after inactivation by UV light. Ad2 and the Ad2+ND2 hybrid, which contains the segment of the SV40 genome between map positions 0.11 and 0.43, were not oncogenic after inactivation by UV light. These results showed that the incorporation of a specific segment of SV40 DNA into the Ad2 genome can alter the pathogenesis of the Ad2+ND4 virus by rendering it oncogenic for hamsters."}
{"id": "PMID:224236", "title": "Pleiotropic phenotype of cultured murine cells resistant to maytansine, vincristine, colchicine, and adriamycin.", "content": "A noncloned subline of 3T3FL cells was developed that was resistant to the toxicity of the ansamycin alkaloid maytansine. Culture of 3T3FL cells with serially increasing concentrations of maytansine resulted in a cell line resistant to maytansine at concentrations 118-fold higher than concentrations cytotoxic for parental cells. Resistant cells (3T3r) exhibited cross-resistance to colchicine, vincristine, adriamycin, and, to a lesser extent, cytochalasin B. Studies of binding and uptake of tritiated colchicine suggested that drug resistance of 3T3r cells might reflect decreased uptake of drug without decreased binding to surface receptors. Murine sarcoma virus transformed 3T3r cells less efficiently than 3T3FL cells.", "contents": "Pleiotropic phenotype of cultured murine cells resistant to maytansine, vincristine, colchicine, and adriamycin. A noncloned subline of 3T3FL cells was developed that was resistant to the toxicity of the ansamycin alkaloid maytansine. Culture of 3T3FL cells with serially increasing concentrations of maytansine resulted in a cell line resistant to maytansine at concentrations 118-fold higher than concentrations cytotoxic for parental cells. Resistant cells (3T3r) exhibited cross-resistance to colchicine, vincristine, adriamycin, and, to a lesser extent, cytochalasin B. Studies of binding and uptake of tritiated colchicine suggested that drug resistance of 3T3r cells might reflect decreased uptake of drug without decreased binding to surface receptors. Murine sarcoma virus transformed 3T3r cells less efficiently than 3T3FL cells."}
{"id": "PMID:224238", "title": "Immunocytochemical distribution of mouse mammary tumor virus antigens in BALB/cfC3H mammary epithelium.", "content": "The distribution of mouse mammary tumor virus (MuMTV) antigens was studied in normal, preneoplastic, and neoplastic mammary epithelia from female BALB/cfC3H mice with the use of a polyvalent anti-MuMTV serum and indirect immunoperoxidase techniques. The MuMTV antigens were on the apical surface or in focal cytoplasmic aggregates or diffused throughout the infected cells. As much as 70% of all cells in adenocarcinomas and as much as 100% of all cells in preneoplastic hyperplastic alveolar nodules contained MMTV antigens. Comparable percentages of cells from mammary glands of multiparous mice were MuMTV-positive. Some mammary tissues of nullparous and primiparous mice did not contain detectable MuMTV antigen. The MuMTV antigen-containing cells in lactating mammary glands tended to be in discrete lobuloalveolar clusters surrounded by antigen-negative alveoli. The percentage of MuMTV-positive cells in a given gland was proportional to the amount of virus found in the animal's milk.", "contents": "Immunocytochemical distribution of mouse mammary tumor virus antigens in BALB/cfC3H mammary epithelium. The distribution of mouse mammary tumor virus (MuMTV) antigens was studied in normal, preneoplastic, and neoplastic mammary epithelia from female BALB/cfC3H mice with the use of a polyvalent anti-MuMTV serum and indirect immunoperoxidase techniques. The MuMTV antigens were on the apical surface or in focal cytoplasmic aggregates or diffused throughout the infected cells. As much as 70% of all cells in adenocarcinomas and as much as 100% of all cells in preneoplastic hyperplastic alveolar nodules contained MMTV antigens. Comparable percentages of cells from mammary glands of multiparous mice were MuMTV-positive. Some mammary tissues of nullparous and primiparous mice did not contain detectable MuMTV antigen. The MuMTV antigen-containing cells in lactating mammary glands tended to be in discrete lobuloalveolar clusters surrounded by antigen-negative alveoli. The percentage of MuMTV-positive cells in a given gland was proportional to the amount of virus found in the animal's milk."}
{"id": "PMID:224239", "title": "Reduced prevalence of the Luck\u00e9 renal adenocarcinoma in populations of Rana pipiens in Minnesota.", "content": "Northern leopard frogs (Rana pipiens) afflicted with the Luck\u00e9 renal adenocarcinoma virtually disappeared from Minnesota in the autumn of 1977. Frogs from four sites in Minnesota counties (Polk, Otter Tail, Kandiyohi, and Scott) with a previously high prevalence of Luck\u00e9 renal tumor were studied. In the past decade, prevalence averaged 4.2% in 29 collections (total, 1,870 frogs). No tumors were detected in 685 frogs autopsied in the autumn of 1977 by the method of previous studies. Frog collections, each comprised of 20 or more individuals, were compared for the presence or absence of tumor-bearing frogs. Significantly fewer collections contained tumor-bearing frogs in the autumn of 1977 than did collections of previous years.", "contents": "Reduced prevalence of the Luck\u00e9 renal adenocarcinoma in populations of Rana pipiens in Minnesota. Northern leopard frogs (Rana pipiens) afflicted with the Luck\u00e9 renal adenocarcinoma virtually disappeared from Minnesota in the autumn of 1977. Frogs from four sites in Minnesota counties (Polk, Otter Tail, Kandiyohi, and Scott) with a previously high prevalence of Luck\u00e9 renal tumor were studied. In the past decade, prevalence averaged 4.2% in 29 collections (total, 1,870 frogs). No tumors were detected in 685 frogs autopsied in the autumn of 1977 by the method of previous studies. Frog collections, each comprised of 20 or more individuals, were compared for the presence or absence of tumor-bearing frogs. Significantly fewer collections contained tumor-bearing frogs in the autumn of 1977 than did collections of previous years."}
{"id": "PMID:224240", "title": "H-2-dependent regulation of the high level of expression of ecotropic murine leukemia virus.", "content": "Adult B10.Y mice, which are congenic with C57BL/10ScSn ((B10) mice for the H-2 region, expressed a high titer of infectious ecotropic virus in the spleen. F1 hybrids between B10.Y and B10 mice were negative or had very low levels of virus expression. In (B10.Y x B10)F2 segregant mice, the high virus phenotype segregated with the H-2pa haplotype of B10.Y, whereas the virus-negative phenotype was associated with the H-2b haplotype of B10. Molecular hybridization experiments with a selected ecotropic AKR murine leukemia virus cyclic DNA probe indicated that both partner strains possessed ecotropic virus sequences and that the number of sequences present was the same in B10.Y mice as in B10 mice. This finding excluded the possibility that the H-2-related effect might be due to the presence of additional viral structural genes within or close to the H-2 region of B10.Y mice. The level of expression of this endogenous ecotropic virus was therefore affected by regulatory genes of the H-2 region.", "contents": "H-2-dependent regulation of the high level of expression of ecotropic murine leukemia virus. Adult B10.Y mice, which are congenic with C57BL/10ScSn ((B10) mice for the H-2 region, expressed a high titer of infectious ecotropic virus in the spleen. F1 hybrids between B10.Y and B10 mice were negative or had very low levels of virus expression. In (B10.Y x B10)F2 segregant mice, the high virus phenotype segregated with the H-2pa haplotype of B10.Y, whereas the virus-negative phenotype was associated with the H-2b haplotype of B10. Molecular hybridization experiments with a selected ecotropic AKR murine leukemia virus cyclic DNA probe indicated that both partner strains possessed ecotropic virus sequences and that the number of sequences present was the same in B10.Y mice as in B10 mice. This finding excluded the possibility that the H-2-related effect might be due to the presence of additional viral structural genes within or close to the H-2 region of B10.Y mice. The level of expression of this endogenous ecotropic virus was therefore affected by regulatory genes of the H-2 region."}
{"id": "PMID:224243", "title": "[Hormone receptors and hormone action (author's transl)].", "content": "All hormones act only on their target tissues. The ability of a tissue to react to a hormone is due to the presence of a receptor in or at the cell. There are two classes of hormone receptors: those bound to the membrane and those present in the cytosol. Peptide hormones generally act through membrane receptors. The interaction of a hormone with its receptors leads to an activation of the adenylate cyclase and the production of cyclo-AMP, the second messenger. In cases where several hormones act on the same tissue (example: adipose tissue) they must interact with their specific receptors, but presumably with the same adenylate cyclase. This interaction is discussed. The receptors for steroid hormones are not membrane-bound, but present in the cytosol. They are specific proteins which bind the hormone rather tightly. This results in a change in protein conformation, sometimes accompanied by a dimerization; the modified receptor is then transferred to the cell nucleus where it stimulates transcription. The control mechanisms of transcription are discussed; the most probable mode of action is removal of a repressor or repressor-like component from chromatin which results in deinhibition of transcription. mRNA is then produced and translated into protein. Post-transcriptional controls have been postulated, but never unequivocally demonstrated.", "contents": "[Hormone receptors and hormone action (author's transl)]. All hormones act only on their target tissues. The ability of a tissue to react to a hormone is due to the presence of a receptor in or at the cell. There are two classes of hormone receptors: those bound to the membrane and those present in the cytosol. Peptide hormones generally act through membrane receptors. The interaction of a hormone with its receptors leads to an activation of the adenylate cyclase and the production of cyclo-AMP, the second messenger. In cases where several hormones act on the same tissue (example: adipose tissue) they must interact with their specific receptors, but presumably with the same adenylate cyclase. This interaction is discussed. The receptors for steroid hormones are not membrane-bound, but present in the cytosol. They are specific proteins which bind the hormone rather tightly. This results in a change in protein conformation, sometimes accompanied by a dimerization; the modified receptor is then transferred to the cell nucleus where it stimulates transcription. The control mechanisms of transcription are discussed; the most probable mode of action is removal of a repressor or repressor-like component from chromatin which results in deinhibition of transcription. mRNA is then produced and translated into protein. Post-transcriptional controls have been postulated, but never unequivocally demonstrated."}
{"id": "PMID:224244", "title": "[Structure and function of biological membranes (author's transl)].", "content": "Biological membranes are essentially asymmetric two-dimensional solutions of proteins in a bimolecular lipid layer. The overall structure and many physical properties of biological membranes can be explained by the fact that membrane proteins and membrane lipids contain hydrophilic as well as hydrophobic domains. Most biological properties of the membrane are determined by the membrane proteins which can catalyze directional processes. With the membrane protein cytochrome oxidase it will be demonstrated how the three-dimensional arrangement of membrane proteins can be studied by chemical, fluorometric, and electron optical methods. However, it is in most cases still impossible to explain the function of a membrane on the basis of its molecular architecture.", "contents": "[Structure and function of biological membranes (author's transl)]. Biological membranes are essentially asymmetric two-dimensional solutions of proteins in a bimolecular lipid layer. The overall structure and many physical properties of biological membranes can be explained by the fact that membrane proteins and membrane lipids contain hydrophilic as well as hydrophobic domains. Most biological properties of the membrane are determined by the membrane proteins which can catalyze directional processes. With the membrane protein cytochrome oxidase it will be demonstrated how the three-dimensional arrangement of membrane proteins can be studied by chemical, fluorometric, and electron optical methods. However, it is in most cases still impossible to explain the function of a membrane on the basis of its molecular architecture."}
{"id": "PMID:224245", "title": "[On the physiology and pharmacology of endorphins (author's transl)].", "content": "Endorphins are peptides with opiate-like action synthesized in various tissue, e.g. in intestine and central nervous system. Exact characterization of opioid-specific receptors and sensitive biological test assays for opioids were prerequisites for the discovery of these substances. Met- and leu-enkephalin were the first endorphins discovered. Both are pentapeptides. One of them, namely met-enkephalin (H-Tyr-Gly-Gyl-Phe-Met-OH) is likely to be a fragment of the peptides alpha- and beta-endorphin, both showing opioid-like actions, as well as of beta-lipotropin, a polypeptide showing no opioid-like activity: all these peptides include the pentapeptide met-enkephalin within their molecules. beta-liportropin and ACTH are likely to be fragments of a common precursor. At least both enkephalins (which are studied better as yet than the other endorphins) are supposed to be formed in the soma of the neuron and transported to the nerve ending, where they are released. They seem to have the function of neuromodulator or even of neurotransmitters. The pharmacological actions of endorphins resemble those of \"classical opiates\", both having e.g. analgesic effects. Both enkephalins are, among various other brain and spinal cord areas, localized in those areas which seem to be of particular relevance for perception and transmission of pain. They might, under certain conditions, play some part in the regulation of pain perception. Furthermore, they seem to be relevant for some neuroendocrine processes. Their relevance in symptoms of schizophrenic psychoses seems to be more doubtful. In opiate dependence no significant alterations of endorphin concentrations could be observed as yet.", "contents": "[On the physiology and pharmacology of endorphins (author's transl)]. Endorphins are peptides with opiate-like action synthesized in various tissue, e.g. in intestine and central nervous system. Exact characterization of opioid-specific receptors and sensitive biological test assays for opioids were prerequisites for the discovery of these substances. Met- and leu-enkephalin were the first endorphins discovered. Both are pentapeptides. One of them, namely met-enkephalin (H-Tyr-Gly-Gyl-Phe-Met-OH) is likely to be a fragment of the peptides alpha- and beta-endorphin, both showing opioid-like actions, as well as of beta-lipotropin, a polypeptide showing no opioid-like activity: all these peptides include the pentapeptide met-enkephalin within their molecules. beta-liportropin and ACTH are likely to be fragments of a common precursor. At least both enkephalins (which are studied better as yet than the other endorphins) are supposed to be formed in the soma of the neuron and transported to the nerve ending, where they are released. They seem to have the function of neuromodulator or even of neurotransmitters. The pharmacological actions of endorphins resemble those of \"classical opiates\", both having e.g. analgesic effects. Both enkephalins are, among various other brain and spinal cord areas, localized in those areas which seem to be of particular relevance for perception and transmission of pain. They might, under certain conditions, play some part in the regulation of pain perception. Furthermore, they seem to be relevant for some neuroendocrine processes. Their relevance in symptoms of schizophrenic psychoses seems to be more doubtful. In opiate dependence no significant alterations of endorphin concentrations could be observed as yet."}
{"id": "PMID:224246", "title": "Catecholamine secreting tumor of the glomus jugulare.", "content": "A case of endocrinologically active glomus jugulare is presented. The localization within the tumor of the catecholamine hyperproduction was demonstrated by selective venous sampling from the vena jugularis externa draining the tumor. The norepinephrine/epinephrine ratio was high and of the same order in blood, urine and cerebrospinal fluid. Bioassay showed high levels of intratumoral norepinephrine and epinephrine. The ways of treatment and their influence on the catecholamines are briefly discussed. In every phaeochromocytoma-like syndrome both the existence of catecholamine hyperproduction and the anatomical site of this hypersecretion have to be precisely documented in order to define the correct treatment to be applied.", "contents": "Catecholamine secreting tumor of the glomus jugulare. A case of endocrinologically active glomus jugulare is presented. The localization within the tumor of the catecholamine hyperproduction was demonstrated by selective venous sampling from the vena jugularis externa draining the tumor. The norepinephrine/epinephrine ratio was high and of the same order in blood, urine and cerebrospinal fluid. Bioassay showed high levels of intratumoral norepinephrine and epinephrine. The ways of treatment and their influence on the catecholamines are briefly discussed. In every phaeochromocytoma-like syndrome both the existence of catecholamine hyperproduction and the anatomical site of this hypersecretion have to be precisely documented in order to define the correct treatment to be applied."}
{"id": "PMID:224263", "title": "Effects of experimental marijuana and tobacco smoke inhalation on alveolar macrophages. A comparative stereologic study.", "content": "Male rats were exposed for 30 consecutive days to whole smoke from either marijuana or tobacco cigarettes. At the end of this period, anesthetized animals from the two smoke-exposed groups together with their age-matched, nonexposed controls underwent bronchopulmonary lavage, and the free lung cells obtained were fixed and collected for light and electron microscopy. Measurements made on 1-micrometer. sections indicated slight, but statistically nonsignificant, shifts in the frequency distributions of alveolar macrophage profile diameters after both exposure regimens. Stereologic techniques were used to study the subcellular morphology of alveolar macrophages from the three groups of animals. Statistically significant changes were found in cells from tobacco-exposed animals in the volume densities of mitochondria, lipid inclusions, lysosomes, remaining cytoplasm, and the surface to volume ratio of the cell. In contrast, only two parameters in the cells from marijuana-exposed animals were found to have changed significantly, with a 3-fold increase in the volume density of lipid inclusions and a slight reduction in the volume density of the remaining cytoplasm. Possible reasons for the differences in the response of the cells in the two smoke-exposed groups are discussed.", "contents": "Effects of experimental marijuana and tobacco smoke inhalation on alveolar macrophages. A comparative stereologic study. Male rats were exposed for 30 consecutive days to whole smoke from either marijuana or tobacco cigarettes. At the end of this period, anesthetized animals from the two smoke-exposed groups together with their age-matched, nonexposed controls underwent bronchopulmonary lavage, and the free lung cells obtained were fixed and collected for light and electron microscopy. Measurements made on 1-micrometer. sections indicated slight, but statistically nonsignificant, shifts in the frequency distributions of alveolar macrophage profile diameters after both exposure regimens. Stereologic techniques were used to study the subcellular morphology of alveolar macrophages from the three groups of animals. Statistically significant changes were found in cells from tobacco-exposed animals in the volume densities of mitochondria, lipid inclusions, lysosomes, remaining cytoplasm, and the surface to volume ratio of the cell. In contrast, only two parameters in the cells from marijuana-exposed animals were found to have changed significantly, with a 3-fold increase in the volume density of lipid inclusions and a slight reduction in the volume density of the remaining cytoplasm. Possible reasons for the differences in the response of the cells in the two smoke-exposed groups are discussed."}
{"id": "PMID:224268", "title": "Lithium antagonism of ethanol-induced depletion of cerebellar guanosine-3',5'-cyclic monophosphate and stimulation of striatal dopamine release.", "content": "Long-term lithium treatment antagonized the behavioral intoxication, depletion of cerebellar guanosine-3,5'-cyclic monophosphate and stimulation of striatal dopamine release induced by a single dose of ethanol. Blood ethanol concentrations were significantly reduced after lithium treatment in a dose-dependent manner.", "contents": "Lithium antagonism of ethanol-induced depletion of cerebellar guanosine-3',5'-cyclic monophosphate and stimulation of striatal dopamine release. Long-term lithium treatment antagonized the behavioral intoxication, depletion of cerebellar guanosine-3,5'-cyclic monophosphate and stimulation of striatal dopamine release induced by a single dose of ethanol. Blood ethanol concentrations were significantly reduced after lithium treatment in a dose-dependent manner."}
{"id": "PMID:224284", "title": "Pathogenesis of Hobbs' heat-sensitive spore forming Clostridium perfringens type A strain.", "content": "Food poisoning in man due to heat-sensitive strains of Cl. perfringens type A appeared to be mediated through enterotoxin synthesized in vivo during sporulation. A minimum of 2.0 X 10(5) vegetative cells suspended in sporulation medium was sufficient to elicit gut-loop response in rabbits. The functional disturbance in the gut as well as the structural changes were progressive and proportional to the size of the inoculum up to a dose limit of 2.0 X 10(7) vegetative cells and beyond this the changes remained steady.", "contents": "Pathogenesis of Hobbs' heat-sensitive spore forming Clostridium perfringens type A strain. Food poisoning in man due to heat-sensitive strains of Cl. perfringens type A appeared to be mediated through enterotoxin synthesized in vivo during sporulation. A minimum of 2.0 X 10(5) vegetative cells suspended in sporulation medium was sufficient to elicit gut-loop response in rabbits. The functional disturbance in the gut as well as the structural changes were progressive and proportional to the size of the inoculum up to a dose limit of 2.0 X 10(7) vegetative cells and beyond this the changes remained steady."}
{"id": "PMID:224287", "title": "Induction of pre-early nuclear antigen(s) in HEL cells infected with human cytomegalovirus.", "content": "Human cytomegalovirus (HCMV)-specific nuclear antigen could be detected within 1 hr after infection in human embryo lung cells by the anticomplement immunofluorescence (ACIF) test. This antigen has been named the pre-early nuclear antigen (PENA) in this paper. Serum absorption tests suggested that PENA is immunologically different from the early antigen and the major nuclear inclusion antigens detected by the indirect immunofluorescence test before and after viral DNA replication, respectively. PENA-forming ability of the virus corresponded to its plaque forming ability. PENA formation was not affected by phosphonoacetate but was inhibited by the addition of inhibitors of RNA and protein syntheses or by UV-irradiation of infecting virus, suggesting that the formation of PENA depends on the expression of infecting virus gene functions. Virus-specific proteins were isolated by indirect immunoprecipitation from HCMV-infected cells exposed to 35S-methionine. SDS-polyacrylamide gel electrophoresis of the immunoprecipitate showed that at least two species of virus-specific polypeptides with molecular weights o.f 70,000 and 30,000 were synthesized de novo within 3 hr after infection.", "contents": "Induction of pre-early nuclear antigen(s) in HEL cells infected with human cytomegalovirus. Human cytomegalovirus (HCMV)-specific nuclear antigen could be detected within 1 hr after infection in human embryo lung cells by the anticomplement immunofluorescence (ACIF) test. This antigen has been named the pre-early nuclear antigen (PENA) in this paper. Serum absorption tests suggested that PENA is immunologically different from the early antigen and the major nuclear inclusion antigens detected by the indirect immunofluorescence test before and after viral DNA replication, respectively. PENA-forming ability of the virus corresponded to its plaque forming ability. PENA formation was not affected by phosphonoacetate but was inhibited by the addition of inhibitors of RNA and protein syntheses or by UV-irradiation of infecting virus, suggesting that the formation of PENA depends on the expression of infecting virus gene functions. Virus-specific proteins were isolated by indirect immunoprecipitation from HCMV-infected cells exposed to 35S-methionine. SDS-polyacrylamide gel electrophoresis of the immunoprecipitate showed that at least two species of virus-specific polypeptides with molecular weights o.f 70,000 and 30,000 were synthesized de novo within 3 hr after infection."}
{"id": "PMID:224291", "title": "[Comparative study of the analysis of lipoproteins with different electrophoretic methods (author's transl)].", "content": "In 100 unselected sera the lipids were analysed with different methods. A commonly used method of the lipoprotein-electrophoresis, which evaluates the pherogram after staining with lipid-strains, was compared with the quantitative lipoproteinelectrophoresis according to Wieland and Seidel. The analyses were supplemented through the enzymatic estimation of total cholesterol and triglycerides. Only in 55 cases the results were identical. The improved diagnosis of lipoproteins is due to the complete and reproducible demonstration of HDL (high density lipoproteins) bands, which are found with the staining methods only in half of the cases. On the contrary the relative proportion of the VLDL (very low density lipoproteins) is increased three-fold with the staining methods.", "contents": "[Comparative study of the analysis of lipoproteins with different electrophoretic methods (author's transl)]. In 100 unselected sera the lipids were analysed with different methods. A commonly used method of the lipoprotein-electrophoresis, which evaluates the pherogram after staining with lipid-strains, was compared with the quantitative lipoproteinelectrophoresis according to Wieland and Seidel. The analyses were supplemented through the enzymatic estimation of total cholesterol and triglycerides. Only in 55 cases the results were identical. The improved diagnosis of lipoproteins is due to the complete and reproducible demonstration of HDL (high density lipoproteins) bands, which are found with the staining methods only in half of the cases. On the contrary the relative proportion of the VLDL (very low density lipoproteins) is increased three-fold with the staining methods."}
{"id": "PMID:224292", "title": "[Defective organification of iodine in an infant demonstrated with 123J and gamma camera (author's transl)].", "content": "A defective organification of iodine is demonstrated in a two year old male infant. The availability and a relatively simple radiation detector and storage system (gamma camera and 1600 word memory) gives a reasonable low radiation dose, allows correction for extrathyroid neck activity and obviates problems of collimation.", "contents": "[Defective organification of iodine in an infant demonstrated with 123J and gamma camera (author's transl)]. A defective organification of iodine is demonstrated in a two year old male infant. The availability and a relatively simple radiation detector and storage system (gamma camera and 1600 word memory) gives a reasonable low radiation dose, allows correction for extrathyroid neck activity and obviates problems of collimation."}
{"id": "PMID:224289", "title": "Do adenine derivatives have a special role in biological regulation?", "content": "The hypothesis is raised \"that adenine by way of its many derivatives plays an important role in regulating a wide variety of biological functions\". Evidence is cited for such a role in cell-to-cell communication, intracellular regulation and interorganism communication. It is predicted that many more key biological functions will be found to be modulated by adenine derivatives and that adenine compounds which have not yet been studied in great depth will become recognized as biological regulators. The hypothesis also predicts that some disease states may be caused by perturbations of the adenine derivative-receptor system.", "contents": "Do adenine derivatives have a special role in biological regulation? The hypothesis is raised \"that adenine by way of its many derivatives plays an important role in regulating a wide variety of biological functions\". Evidence is cited for such a role in cell-to-cell communication, intracellular regulation and interorganism communication. It is predicted that many more key biological functions will be found to be modulated by adenine derivatives and that adenine compounds which have not yet been studied in great depth will become recognized as biological regulators. The hypothesis also predicts that some disease states may be caused by perturbations of the adenine derivative-receptor system."}
{"id": "PMID:224288", "title": "[Electron microscopic study of normal Bacillus anthracoides spores and after exposure to a chloroactive disinfectant].", "content": "The fine structure of Bacillus anthracoides spores is similar in general to that of other, taxonomically related species of spore forming bacteria. However, the former is characterized by a well-developed multilayered exosporium and the heterogeneous structure of an envelope. The lethal effect of a chloroactive disinfectant (2/3 of calcium hypochlorite basic salt) is caused by changes in the structural organization of spores, which interferes with the normal permeability barrier and metabolic processes.", "contents": "[Electron microscopic study of normal Bacillus anthracoides spores and after exposure to a chloroactive disinfectant]. The fine structure of Bacillus anthracoides spores is similar in general to that of other, taxonomically related species of spore forming bacteria. However, the former is characterized by a well-developed multilayered exosporium and the heterogeneous structure of an envelope. The lethal effect of a chloroactive disinfectant (2/3 of calcium hypochlorite basic salt) is caused by changes in the structural organization of spores, which interferes with the normal permeability barrier and metabolic processes."}
{"id": "PMID:224294", "title": "[Investigations concerning the hypothalamic-hypophysial regulation of aldosterone secretion (author's transl)].", "content": "In 17 patients with retrospectively healthy adrenals we performed a LHRH-test, a TRF-test and an ACTH-test in the short modification. Additionally we determined plasma aldosterone and renine levels. Concerning the LHRH-tests and the TRF-tests we did not find any differences on the aldosterone values. Concerning the ACTH-tests in the short modification we found an increase of the aldosterone values which resembled that of the cortisol levels (increase of cortisol 104.7%, increase of aldosterone 93.3%). The renin values remained unchanged. Therefore the plasma aldosterone levels are modified in accordance with the cortisol levels by hypophysial influences.", "contents": "[Investigations concerning the hypothalamic-hypophysial regulation of aldosterone secretion (author's transl)]. In 17 patients with retrospectively healthy adrenals we performed a LHRH-test, a TRF-test and an ACTH-test in the short modification. Additionally we determined plasma aldosterone and renine levels. Concerning the LHRH-tests and the TRF-tests we did not find any differences on the aldosterone values. Concerning the ACTH-tests in the short modification we found an increase of the aldosterone values which resembled that of the cortisol levels (increase of cortisol 104.7%, increase of aldosterone 93.3%). The renin values remained unchanged. Therefore the plasma aldosterone levels are modified in accordance with the cortisol levels by hypophysial influences."}
{"id": "PMID:224296", "title": "Normal and pseudorabies virus infected primary nerve cell cultures in scanning electron microscopy.", "content": "Primary cell cultures from the central nervous system of the embryonic rat were inoculated with pseudorabies virus. Their morphological changes were studied by phase contrast microscopy and by scanning as well as by transmission electron microscopy. Uninfected cultures display two distinct cell layers in scanning electron microscopy: a flat continuous monolayer supports a heterogeneous population of individual, presumably neural cells, which emit processes of different number and size. The latter cells form contacts by a dense network of fibres. Infectious virus is propagated in these nerve cell cultures with similar effectivity as in other cultures. The infectoin leads to fusion and death of the cells. By the time the cytopathic effect is visible, nearly all cells, including those of neuronal and those of nonneuronal appearance, are studded with ample amounts of virus-sized particles. The particles represent viruses as demonstrated by transmission electron microscopy or by treatment with a hyperimmune serum directed against pseudorabies virus structural components. Hyperimmune serum leads to clustering of the particles at the cell surface. The amount of virus particles per surface unit was about 10 times higher on neural cells as compared to primary rabbit kidney cells. The concentration of infectious particles in the supernatant, however was approximately the same. The system described appears to be useful for the study of acute virus effects on neural tissue under strictly controlled conditions.", "contents": "Normal and pseudorabies virus infected primary nerve cell cultures in scanning electron microscopy. Primary cell cultures from the central nervous system of the embryonic rat were inoculated with pseudorabies virus. Their morphological changes were studied by phase contrast microscopy and by scanning as well as by transmission electron microscopy. Uninfected cultures display two distinct cell layers in scanning electron microscopy: a flat continuous monolayer supports a heterogeneous population of individual, presumably neural cells, which emit processes of different number and size. The latter cells form contacts by a dense network of fibres. Infectious virus is propagated in these nerve cell cultures with similar effectivity as in other cultures. The infectoin leads to fusion and death of the cells. By the time the cytopathic effect is visible, nearly all cells, including those of neuronal and those of nonneuronal appearance, are studded with ample amounts of virus-sized particles. The particles represent viruses as demonstrated by transmission electron microscopy or by treatment with a hyperimmune serum directed against pseudorabies virus structural components. Hyperimmune serum leads to clustering of the particles at the cell surface. The amount of virus particles per surface unit was about 10 times higher on neural cells as compared to primary rabbit kidney cells. The concentration of infectious particles in the supernatant, however was approximately the same. The system described appears to be useful for the study of acute virus effects on neural tissue under strictly controlled conditions."}
{"id": "PMID:224304", "title": "Canine viral enteritis. Recent developments.", "content": "Two apparently novel viral gastroenteritides of dogs were recognized in 1978: one caused by a parvo-like virus (CPV) and one by a corona-like virus (CCV). A rotavirus has also been tentatively associated with neonatal pup enteritis. Canine viral enteritis is characterized by a sudden onset of vomiting and diarrhea, rapid spread and high morbidity. Treatment is only supportive but must be initiated promptly. Infected animals should be isolated immediately; the extremely contagious nature of these diseases makes them difficult to contain. Feces from infected dogs appear to be the primary means of transmission. Sodium hypochlorite solutions (eg, Clorox) are recommended for disinfection. The development of effective vaccines is an immediate and pressing problem.", "contents": "Canine viral enteritis. Recent developments. Two apparently novel viral gastroenteritides of dogs were recognized in 1978: one caused by a parvo-like virus (CPV) and one by a corona-like virus (CCV). A rotavirus has also been tentatively associated with neonatal pup enteritis. Canine viral enteritis is characterized by a sudden onset of vomiting and diarrhea, rapid spread and high morbidity. Treatment is only supportive but must be initiated promptly. Infected animals should be isolated immediately; the extremely contagious nature of these diseases makes them difficult to contain. Feces from infected dogs appear to be the primary means of transmission. Sodium hypochlorite solutions (eg, Clorox) are recommended for disinfection. The development of effective vaccines is an immediate and pressing problem."}
{"id": "PMID:224302", "title": "[Scanning microscopic study of the action of perchloric acid on emptying of the pulporadicular cavity].", "content": "Following a rapid review of techniques of mechanical and chemical emptying of the pulporadicular cavity, the use of perchloric acid and hypochlorite of sodium and oxygenated water is described by means of scan microscope histological slides.", "contents": "[Scanning microscopic study of the action of perchloric acid on emptying of the pulporadicular cavity]. Following a rapid review of techniques of mechanical and chemical emptying of the pulporadicular cavity, the use of perchloric acid and hypochlorite of sodium and oxygenated water is described by means of scan microscope histological slides."}
{"id": "PMID:224310", "title": "[New results on hyperglobulinemic purpura of Waldenstr\u00f6m in childhood (author's transl)].", "content": "The case of a 13 year old girl with benign purpura hypergammaglobulinemica Waldenstr\u00f6m. Besides the characteristic clinical symptoms and the respective laboratory results new findings we demonstrated, which might shed some light into the pathogenesis of this disease. The transformation rate of lymphocytes was decreased particularly after stimulation with ConA. The T-lymphocytes which are reduced in their function are unable to sufficiently control the activity of mesenchymal cells which results in an increased production of glycosaminoglycans. The demonstration of glycosaminoglycan-inclusion-bodies in the mononuclear bone marrow cells of the patient could be explained by the above mentioned mechanism. Upon therapy with D-penicillamine the clinical state improved along with a reduction of the sedimentation rate, the serum protein and the serum gamma-globulin.", "contents": "[New results on hyperglobulinemic purpura of Waldenstr\u00f6m in childhood (author's transl)]. The case of a 13 year old girl with benign purpura hypergammaglobulinemica Waldenstr\u00f6m. Besides the characteristic clinical symptoms and the respective laboratory results new findings we demonstrated, which might shed some light into the pathogenesis of this disease. The transformation rate of lymphocytes was decreased particularly after stimulation with ConA. The T-lymphocytes which are reduced in their function are unable to sufficiently control the activity of mesenchymal cells which results in an increased production of glycosaminoglycans. The demonstration of glycosaminoglycan-inclusion-bodies in the mononuclear bone marrow cells of the patient could be explained by the above mentioned mechanism. Upon therapy with D-penicillamine the clinical state improved along with a reduction of the sedimentation rate, the serum protein and the serum gamma-globulin."}
{"id": "PMID:224308", "title": "[Covalent bond between RNA and protein in encephalomyocarditis virus].", "content": "Deproteinized encephalomyocarditis [32P]RNA, after digestion with a mixture of RNases A, T1 and T2, yields mononucleotides and a labelled compound, which is positively charged at pH 3.5. This product can be digested with pronase and has a close electrophoretic mobility to a protein with a molecular weight of 7000-8000. Covalently bound nucleotide-peptides were isolated from this compound after treatment with RNases and pronase. It was shown that the 5'-terminal uridylic acid is covalently linked with peptides. The phosphodiester bond between uridylic acid and peptides is discussed.", "contents": "[Covalent bond between RNA and protein in encephalomyocarditis virus]. Deproteinized encephalomyocarditis [32P]RNA, after digestion with a mixture of RNases A, T1 and T2, yields mononucleotides and a labelled compound, which is positively charged at pH 3.5. This product can be digested with pronase and has a close electrophoretic mobility to a protein with a molecular weight of 7000-8000. Covalently bound nucleotide-peptides were isolated from this compound after treatment with RNases and pronase. It was shown that the 5'-terminal uridylic acid is covalently linked with peptides. The phosphodiester bond between uridylic acid and peptides is discussed."}
{"id": "PMID:224322", "title": "Evidence for the release of endogenous substance P from intestinal nerves.", "content": "The desensitization of receptors for substance P in the longitudinal muscle of the guinea-pig ileum has been studied. Receptors for substance P in the muscle became desensitized in the presence of relatively large concentrations of synthetic substance P; a desensitizing concentration of substance P of 7.5 x 10(-9) M shifted the concentration-response curve for substance P about 20-fold to the right, while a desensitizing concentration of 7.5 x 10(-8) M shifted the curve about 300-fold to the right. This desensitization appeared specific; concentration-response curves for carbachol, DMPP, 5-HT and bradykinin were not significantly affected by substance P, 7.5 x 10(-8) M. Furthermore, substance P in concentrations up to 7.5 x 10(-8) M did not modify transmission from either cholinergic nerves or enteric inhibitory nerves when these were stimulated electrically. However, hyoscine-resistant contractions produced by stimulation of nerves in the ileum at 10 Hz were abolished by exposure to concentrations of substance P of 7.5 x 10(-9) M or greater, suggesting that these nerves release a substance similar to or identical with substance P. DMPP evoked small hyoscine-resistant contractions of the ileum. These contractions were also antagonised by desensitization of receptors for substance P. Immunohistochemical studies showed substance P-like immunoreactivity in nerve terminals of both the myenteric and submucous plexuses.", "contents": "Evidence for the release of endogenous substance P from intestinal nerves. The desensitization of receptors for substance P in the longitudinal muscle of the guinea-pig ileum has been studied. Receptors for substance P in the muscle became desensitized in the presence of relatively large concentrations of synthetic substance P; a desensitizing concentration of substance P of 7.5 x 10(-9) M shifted the concentration-response curve for substance P about 20-fold to the right, while a desensitizing concentration of 7.5 x 10(-8) M shifted the curve about 300-fold to the right. This desensitization appeared specific; concentration-response curves for carbachol, DMPP, 5-HT and bradykinin were not significantly affected by substance P, 7.5 x 10(-8) M. Furthermore, substance P in concentrations up to 7.5 x 10(-8) M did not modify transmission from either cholinergic nerves or enteric inhibitory nerves when these were stimulated electrically. However, hyoscine-resistant contractions produced by stimulation of nerves in the ileum at 10 Hz were abolished by exposure to concentrations of substance P of 7.5 x 10(-9) M or greater, suggesting that these nerves release a substance similar to or identical with substance P. DMPP evoked small hyoscine-resistant contractions of the ileum. These contractions were also antagonised by desensitization of receptors for substance P. Immunohistochemical studies showed substance P-like immunoreactivity in nerve terminals of both the myenteric and submucous plexuses."}
{"id": "PMID:224326", "title": "[Structure and correlation of \"fast\" and \"slow\" background impulse activity of visual cortex neurons].", "content": "Background and optically modified impulse activity of neurons in visual cortex of unanaesthetized rabbits was analyzed. By means of joint interval histograms it was shown that neurons can be distinguished by the ratio of burts (intervals to 15-40 ms) and extraburst activity and by the shape of transition from one from of activity to another. The extraburst activity comprises 63% of impulses and its ratio to bursts of 2 or 3 and more impulses was 27:3:1. Burts impulse distribution showed a relative stability of timing pattern within bursts and small number of burst impulses (2.4 on the average). Bursts of 3 and more impulses (3.6 on the average) are not rhythmical and 79% of them contained long intervals (18.6 +/- 2.4 ms) before the shortest one (7.9 +/- 0.9 ms). Optical stimulation resulted in bursts containing core impulses, shorter intervals and beginning with the shortest interval in most neurons. This may testify to the increase of the EPSP steepness and amplitude. 20% of cortical neurons showed background bursts containing more impulses and shorter intervals in comparison with evoked bursts.", "contents": "[Structure and correlation of \"fast\" and \"slow\" background impulse activity of visual cortex neurons]. Background and optically modified impulse activity of neurons in visual cortex of unanaesthetized rabbits was analyzed. By means of joint interval histograms it was shown that neurons can be distinguished by the ratio of burts (intervals to 15-40 ms) and extraburst activity and by the shape of transition from one from of activity to another. The extraburst activity comprises 63% of impulses and its ratio to bursts of 2 or 3 and more impulses was 27:3:1. Burts impulse distribution showed a relative stability of timing pattern within bursts and small number of burst impulses (2.4 on the average). Bursts of 3 and more impulses (3.6 on the average) are not rhythmical and 79% of them contained long intervals (18.6 +/- 2.4 ms) before the shortest one (7.9 +/- 0.9 ms). Optical stimulation resulted in bursts containing core impulses, shorter intervals and beginning with the shortest interval in most neurons. This may testify to the increase of the EPSP steepness and amplitude. 20% of cortical neurons showed background bursts containing more impulses and shorter intervals in comparison with evoked bursts."}
{"id": "PMID:224327", "title": "[Polysynaptic effects in neurons of the cervical portion of the cat spinal cord induced by activation of long propriospinal pathways].", "content": "Effects evoked in cervical moto- and interneurons by stimulation of lateral (LF) and ventral (VF) funicles at low thoracic level were studied in anaesthetized cats; degeneration of descending supraspinal fibres was provided by preliminary cord sections. LF and (or) VF stimulation evoked PSPs (usually mixed) in 57 of 90 studied motoneurons. Monosynaptic EPSPs were \"primary\" actions in 9 motoneurons while poly(di)-synaptic EPSPs or IPSPs--in the rest. Intensity of excitatory synaptic action on motoneurons of proximal muscles was substantially higher than on \"distal\" ones. LF and VF stimulation excited interneurons localized in the ventral quadrant and had no action on interneurons situated more dorsally. The effects studied are suggested to be mainly a result of activation of long proporiospinal fibres ascending via LF and VF to the cervical enlargement; certain part of reactions is supposed to be transmitted via collaterals of descending propriospinal fibres to the cervical neurons.", "contents": "[Polysynaptic effects in neurons of the cervical portion of the cat spinal cord induced by activation of long propriospinal pathways]. Effects evoked in cervical moto- and interneurons by stimulation of lateral (LF) and ventral (VF) funicles at low thoracic level were studied in anaesthetized cats; degeneration of descending supraspinal fibres was provided by preliminary cord sections. LF and (or) VF stimulation evoked PSPs (usually mixed) in 57 of 90 studied motoneurons. Monosynaptic EPSPs were \"primary\" actions in 9 motoneurons while poly(di)-synaptic EPSPs or IPSPs--in the rest. Intensity of excitatory synaptic action on motoneurons of proximal muscles was substantially higher than on \"distal\" ones. LF and VF stimulation excited interneurons localized in the ventral quadrant and had no action on interneurons situated more dorsally. The effects studied are suggested to be mainly a result of activation of long proporiospinal fibres ascending via LF and VF to the cervical enlargement; certain part of reactions is supposed to be transmitted via collaterals of descending propriospinal fibres to the cervical neurons."}
{"id": "PMID:224328", "title": "[Display of a monosynaptic excitatory connection in the structure of a crosscorrelation histogram].", "content": "Reflection of the monosynaptic excitatory connection in the cross correlation histogram structure was investigated using mathematical model of neuron interactions. The peculiar features of crosscorrelation histogram primary peak waveform and situation permitting distinguishing the monosynaptic excitatory connection from the monosynaptic excitatory shared input were described. Variation of primary peak magnitude with the model parameters describing mechanisms of the action potential generation and synaptic excitation transmission was shown. The autocorrelation histogram structure is shown to be reflected in the crosscorrelation histogram structure on both sides of the primary peak and to take part in the forming of secondary peaks and troughs.", "contents": "[Display of a monosynaptic excitatory connection in the structure of a crosscorrelation histogram]. Reflection of the monosynaptic excitatory connection in the cross correlation histogram structure was investigated using mathematical model of neuron interactions. The peculiar features of crosscorrelation histogram primary peak waveform and situation permitting distinguishing the monosynaptic excitatory connection from the monosynaptic excitatory shared input were described. Variation of primary peak magnitude with the model parameters describing mechanisms of the action potential generation and synaptic excitation transmission was shown. The autocorrelation histogram structure is shown to be reflected in the crosscorrelation histogram structure on both sides of the primary peak and to take part in the forming of secondary peaks and troughs."}
{"id": "PMID:224330", "title": "EBV-specific humoral antibodies in nasopharyngeal carcinoma patients in Cuba.", "content": "Sera of 24 patients with nasopharyngeal carcinoma (NPC) and of 60 healthy donors were studied for presence of IgG and IgA antibodies against different antigens induced by Epstein--Barr virus (EBV). The results obtained demonstrate that NPC in Cuba, as in other countries, is accompanied by elevated antibody titers against EBV-specific IgG antibodies, whose levels strongly differ from those of healthy persons. Patients with NPC in Cuba had higher titers of antibody against VCA of EBV in comparison with patients of Caucasian origin in those countries where NPC, the same as in cuba, is rarely found. Cuban NPC patients had high levels of antibody against EA, often higher than in NPC patients in endemic zones of this disease.", "contents": "EBV-specific humoral antibodies in nasopharyngeal carcinoma patients in Cuba. Sera of 24 patients with nasopharyngeal carcinoma (NPC) and of 60 healthy donors were studied for presence of IgG and IgA antibodies against different antigens induced by Epstein--Barr virus (EBV). The results obtained demonstrate that NPC in Cuba, as in other countries, is accompanied by elevated antibody titers against EBV-specific IgG antibodies, whose levels strongly differ from those of healthy persons. Patients with NPC in Cuba had higher titers of antibody against VCA of EBV in comparison with patients of Caucasian origin in those countries where NPC, the same as in cuba, is rarely found. Cuban NPC patients had high levels of antibody against EA, often higher than in NPC patients in endemic zones of this disease."}
{"id": "PMID:224333", "title": "[Downward migration of the optic system after transsphenoidal approach of a giant eosinophilic adenoma (author's transl)].", "content": "Headache and visual impairment resulting from downward migration of the optic system in an acromegalic patient, occurred after one year postoperatively. A 25-year-old woman with eosinophilic adenoma was operated on via transsphenoidal approach and irradiated (5,000 rads) following the operation. After the operation, bitemporal hemianopia was thoroughly improved and serum HGH level was also markedly decreased after radiation therapy. One year later, headache and visual impairment recurred. Pneumoencephalogram revealed that the infundibular and optic recessus of the third ventricle were elongated and descended into the sella turcica. The second operation was performed by subfrontal approach and the optic system was found to be migrated into the sella, which we assumed to be the cause for the recurrence of the headache and visual field defect. In order to prevent this type of complication, it would be recommended to fill up the dead space in the sella with bone or cartilage fragments in addition to muscle pieces, as was suggested by Guiot et al.", "contents": "[Downward migration of the optic system after transsphenoidal approach of a giant eosinophilic adenoma (author's transl)]. Headache and visual impairment resulting from downward migration of the optic system in an acromegalic patient, occurred after one year postoperatively. A 25-year-old woman with eosinophilic adenoma was operated on via transsphenoidal approach and irradiated (5,000 rads) following the operation. After the operation, bitemporal hemianopia was thoroughly improved and serum HGH level was also markedly decreased after radiation therapy. One year later, headache and visual impairment recurred. Pneumoencephalogram revealed that the infundibular and optic recessus of the third ventricle were elongated and descended into the sella turcica. The second operation was performed by subfrontal approach and the optic system was found to be migrated into the sella, which we assumed to be the cause for the recurrence of the headache and visual field defect. In order to prevent this type of complication, it would be recommended to fill up the dead space in the sella with bone or cartilage fragments in addition to muscle pieces, as was suggested by Guiot et al."}
{"id": "PMID:224332", "title": "[Hemorrhagic lesion of the sciatic nerve caused by chronic infection and iatrogenic factors].", "content": "The author reports a 50-year-old woman with haemorrhagic lesion to the sciatic nerve during a chronic infectious process and treatment with chemotherapeutic agents. The nerve was damaged by pressure exerted by extravasated blood or haemorrhage from vasa nervorum.", "contents": "[Hemorrhagic lesion of the sciatic nerve caused by chronic infection and iatrogenic factors]. The author reports a 50-year-old woman with haemorrhagic lesion to the sciatic nerve during a chronic infectious process and treatment with chemotherapeutic agents. The nerve was damaged by pressure exerted by extravasated blood or haemorrhage from vasa nervorum."}
{"id": "PMID:224336", "title": "Depression of evoked potentials in rat thalamic ventro-basal complex and somatosensory cortex after reticular stimulation.", "content": "Experiments on unanesthetized rats immobilized with D-tubocurarine showed that electrical stimulation (100/sec) of the central gray matter and the mesencephalic and medullary reticular formation considerably depressed potentials in the somatic thalamic relay nucleus and somatosensory cortex evoked by stimulation of the forelimb or medial lemniscus. The mean threshold values of the current used for electrical stimulation of these structures did not differ significantly and were 70 (20--100), 100(20--120), and 120 (50--200) muA, respectively. On comparison of the amplitude-temporal characteristics of inhibition of evoked potentials during electrical stimulation of the above-mentioned structures by a current of twice the threshold strength, no significant differences were found. Immediately after the end of electrical stimulation the amplitude of the cortical evolved potential and the post-synpatic components of the thalamic evoked potential was 50--60% (P less than 0.01) below the control values. The duration of this depression varied from 0.5 to 1 sec. An increase in the intensity of electrical stimulation of brain-stem structures to between three and five times the threshold led to depression of the presynaptic component of the thalamic evoked potential also. Depression of the evoked potential as described above was found with various ratios between the intensities of conditioning and testing stimuli.", "contents": "Depression of evoked potentials in rat thalamic ventro-basal complex and somatosensory cortex after reticular stimulation. Experiments on unanesthetized rats immobilized with D-tubocurarine showed that electrical stimulation (100/sec) of the central gray matter and the mesencephalic and medullary reticular formation considerably depressed potentials in the somatic thalamic relay nucleus and somatosensory cortex evoked by stimulation of the forelimb or medial lemniscus. The mean threshold values of the current used for electrical stimulation of these structures did not differ significantly and were 70 (20--100), 100(20--120), and 120 (50--200) muA, respectively. On comparison of the amplitude-temporal characteristics of inhibition of evoked potentials during electrical stimulation of the above-mentioned structures by a current of twice the threshold strength, no significant differences were found. Immediately after the end of electrical stimulation the amplitude of the cortical evolved potential and the post-synpatic components of the thalamic evoked potential was 50--60% (P less than 0.01) below the control values. The duration of this depression varied from 0.5 to 1 sec. An increase in the intensity of electrical stimulation of brain-stem structures to between three and five times the threshold led to depression of the presynaptic component of the thalamic evoked potential also. Depression of the evoked potential as described above was found with various ratios between the intensities of conditioning and testing stimuli."}
{"id": "PMID:224341", "title": "Cell-mediated immunity to polio and HLA antigens in amyotrophic lateral sclerosis.", "content": "Cell-mediated immunity to poliovirus was demonstrated in 21 of 33 patients suffering from amyotrophic lateral sclerosis (ALS), whereas no response to poliovirus was found in patients suffering from other neurologic disorders or in healthy controls. Three of the severe bulbar cases produced a migration inhibition factor (MIF) in the presence of poliovirus, although skin tests to common antigens were negative. An increased incidence (46 percent) of HLA-A3 was found in patients with amytrophic lateral sclerosis. Nine of the 13 patients with HLA-A3 antigen also had a positive index of MIF to poliovirus. These findings suggest a strong linkage between HLA-A3 and poliovirus in the pathogenesis of amyotrophic lateral sclerosis.", "contents": "Cell-mediated immunity to polio and HLA antigens in amyotrophic lateral sclerosis. Cell-mediated immunity to poliovirus was demonstrated in 21 of 33 patients suffering from amyotrophic lateral sclerosis (ALS), whereas no response to poliovirus was found in patients suffering from other neurologic disorders or in healthy controls. Three of the severe bulbar cases produced a migration inhibition factor (MIF) in the presence of poliovirus, although skin tests to common antigens were negative. An increased incidence (46 percent) of HLA-A3 was found in patients with amytrophic lateral sclerosis. Nine of the 13 patients with HLA-A3 antigen also had a positive index of MIF to poliovirus. These findings suggest a strong linkage between HLA-A3 and poliovirus in the pathogenesis of amyotrophic lateral sclerosis."}
{"id": "PMID:224339", "title": "Role of adrenergic structures in functional control over the cerebral circulation.", "content": "An investigation of the cerebral circulation by the thermoelectric method showed that stimulation of the cervical sympathetic nerve leads to considerable changes in the blood supply to the brain. The changes in blood flow are biphasic in character: An initial small increase is followed by a decrease below the original level. Pharmacological analysis with alpha and beta adreno-blockers showed that the constrictor response of the cerebral vessels is due to excitation of alpha-adrenergic structures and the dilator response to excitation of beta-adrenergic structures. A possible mechanism of these changes is postulated.", "contents": "Role of adrenergic structures in functional control over the cerebral circulation. An investigation of the cerebral circulation by the thermoelectric method showed that stimulation of the cervical sympathetic nerve leads to considerable changes in the blood supply to the brain. The changes in blood flow are biphasic in character: An initial small increase is followed by a decrease below the original level. Pharmacological analysis with alpha and beta adreno-blockers showed that the constrictor response of the cerebral vessels is due to excitation of alpha-adrenergic structures and the dilator response to excitation of beta-adrenergic structures. A possible mechanism of these changes is postulated."}
{"id": "PMID:224342", "title": "Lactic acidemia, mitochondrial myopathy, and basal ganglia calcification.", "content": "A 27-year-old man had limb weakness, short stature, neurosensory hearing loss, seizures, mild peripheral neuropathy, neurogenic bladder, elevated cerebrospinal fluid (CSF) protein content, primary lactic acidemia, and basal ganglia calcification. Muscle biopsy revealed numerous ragged-red fibers. On electronmicroscopy there were mitochondrial alterations, including many intramitochondrial inclusions. The mother of the patient had Vogt-Koyanagi-Harada syndrome, a combination of rare disorders in the same family that has not been previously described.", "contents": "Lactic acidemia, mitochondrial myopathy, and basal ganglia calcification. A 27-year-old man had limb weakness, short stature, neurosensory hearing loss, seizures, mild peripheral neuropathy, neurogenic bladder, elevated cerebrospinal fluid (CSF) protein content, primary lactic acidemia, and basal ganglia calcification. Muscle biopsy revealed numerous ragged-red fibers. On electronmicroscopy there were mitochondrial alterations, including many intramitochondrial inclusions. The mother of the patient had Vogt-Koyanagi-Harada syndrome, a combination of rare disorders in the same family that has not been previously described."}
{"id": "PMID:224343", "title": "Ephaptic transmission in chronically damaged peripheral nerves.", "content": "Several weeks after damage of the sciatic nerve in adult rats, a stable electrical (ephaptic) interaction forms between pairs of injured sensory and motor axons. Fiber-fiber interaction occurs when the nerve ends in a neuroma, after end-to-end nerve suture and after nerve crush injury. Unlike the transient \"artificial synapse\" created acutely on section of a nerve, this form of crosstalk is long-lasting. Its existence lends support to the hypothesis that ephaptic interaction is an important factor in neurologic pathophysiology.", "contents": "Ephaptic transmission in chronically damaged peripheral nerves. Several weeks after damage of the sciatic nerve in adult rats, a stable electrical (ephaptic) interaction forms between pairs of injured sensory and motor axons. Fiber-fiber interaction occurs when the nerve ends in a neuroma, after end-to-end nerve suture and after nerve crush injury. Unlike the transient \"artificial synapse\" created acutely on section of a nerve, this form of crosstalk is long-lasting. Its existence lends support to the hypothesis that ephaptic interaction is an important factor in neurologic pathophysiology."}
{"id": "PMID:224345", "title": "Peripheral neuropathy in arsenic smelter workers.", "content": "We conducted a double-blind controlled study of individuals exposed to arsenic trioxide in a copper-smelting factory. Subjects fell into three categories of peripheral neuropathy: none, subclinical, and clinical. The subclinical group had no symptoms or signs of numbness or reduced reflexes, but did have reduced nerve conduction velocity and amplitude measurements. Clinical neuropathy groups had signs and symptoms of neuropathy and electrophysiologic abnormalities. The clinical and subclinical groups correlated with increased content of arsenic in urine, hair and nails. The incidence of subclinical and clinical neuropathy was greater in arsenic workers than in unexposed controls.", "contents": "Peripheral neuropathy in arsenic smelter workers. We conducted a double-blind controlled study of individuals exposed to arsenic trioxide in a copper-smelting factory. Subjects fell into three categories of peripheral neuropathy: none, subclinical, and clinical. The subclinical group had no symptoms or signs of numbness or reduced reflexes, but did have reduced nerve conduction velocity and amplitude measurements. Clinical neuropathy groups had signs and symptoms of neuropathy and electrophysiologic abnormalities. The clinical and subclinical groups correlated with increased content of arsenic in urine, hair and nails. The incidence of subclinical and clinical neuropathy was greater in arsenic workers than in unexposed controls."}
{"id": "PMID:224346", "title": "Ethylene oxide neurotoxicity: report of four cases and review of the literature.", "content": "Four workers were exposed to ethylene oxide gas. Acute encephalopathy occurred in one, and peripheral neuropathy in three, two of whom were symptomatic. Nerve conduction velocity studies were abnormal in three, including the asymptomatic patient. Decreasing the amount of exposure resulted in relief of symptoms. The abnormal nerve conduction studies did not change in two patients who continued to work at a lower level of exposure, whereas the conduction abnormalities improved in the patient who was removed from exposure.", "contents": "Ethylene oxide neurotoxicity: report of four cases and review of the literature. Four workers were exposed to ethylene oxide gas. Acute encephalopathy occurred in one, and peripheral neuropathy in three, two of whom were symptomatic. Nerve conduction velocity studies were abnormal in three, including the asymptomatic patient. Decreasing the amount of exposure resulted in relief of symptoms. The abnormal nerve conduction studies did not change in two patients who continued to work at a lower level of exposure, whereas the conduction abnormalities improved in the patient who was removed from exposure."}
{"id": "PMID:224347", "title": "H reflex analysis of segmental reflex excitability in flexor and extensor muscles.", "content": "In normal adults, H reflexes are commonly found only in the antigravity calf and flexor carpi radialis (FCR) muscles. However, these responses may be more widespread if agonist muscles contract. This study demonstrates that H reflexes may be found in the peroneal (P) and anterior tibialis (TA) muscles in the leg and the extensor digitorum communis (EDC) muscle in the arm on contraction of the antagonistic calf and flexor carpi radialis muscles, respectively. H reflexes were also elicited regularly in the EDC by passive extension of the wrist. The data indicate physiologic unity of comparably acting human antigravity muscles and their antagonists in both the upper and lower extremities, and imply an important functional role of group II afferent fibers in normal motor system activity.", "contents": "H reflex analysis of segmental reflex excitability in flexor and extensor muscles. In normal adults, H reflexes are commonly found only in the antigravity calf and flexor carpi radialis (FCR) muscles. However, these responses may be more widespread if agonist muscles contract. This study demonstrates that H reflexes may be found in the peroneal (P) and anterior tibialis (TA) muscles in the leg and the extensor digitorum communis (EDC) muscle in the arm on contraction of the antagonistic calf and flexor carpi radialis muscles, respectively. H reflexes were also elicited regularly in the EDC by passive extension of the wrist. The data indicate physiologic unity of comparably acting human antigravity muscles and their antagonists in both the upper and lower extremities, and imply an important functional role of group II afferent fibers in normal motor system activity."}
{"id": "PMID:224348", "title": "[The role of fiberoptic bronchoscopy in the diagnosis of pulmonary cancer].", "content": "Cancer of the lung is becoming increasingly common. In the U.S., it has the highest mortality of the neoplastic diseases, well ahead of cancer of the colon and rectum. Surgical and/or complementary management is poorly effective because it comes too late. Early diagnosis and treatment are essential, therefore. Preclinical diagnosis may be possible radiographically in certain fortunate cases, but this is never an early diagnosis. The latter is only possible through active bronchial cytology (bronchial brushing, selective washing, PBS) during and after flexible fibrobronchoscopy, which can be carried out under local anaesthesia at the outpatient level and causes very little distress to the patient. Data from a personal series are cited in support of the view that cytodiagnosis should be routinely employed in subjects at high risk (heavy smokers, persons with chronic bronchitis, emphysema, etc.).", "contents": "[The role of fiberoptic bronchoscopy in the diagnosis of pulmonary cancer]. Cancer of the lung is becoming increasingly common. In the U.S., it has the highest mortality of the neoplastic diseases, well ahead of cancer of the colon and rectum. Surgical and/or complementary management is poorly effective because it comes too late. Early diagnosis and treatment are essential, therefore. Preclinical diagnosis may be possible radiographically in certain fortunate cases, but this is never an early diagnosis. The latter is only possible through active bronchial cytology (bronchial brushing, selective washing, PBS) during and after flexible fibrobronchoscopy, which can be carried out under local anaesthesia at the outpatient level and causes very little distress to the patient. Data from a personal series are cited in support of the view that cytodiagnosis should be routinely employed in subjects at high risk (heavy smokers, persons with chronic bronchitis, emphysema, etc.)."}
{"id": "PMID:224349", "title": "[Criteria of surgical treatment in 148 cases of recto-sigmoid cancer].", "content": "The clinical aspects of cancer of the rectum and sigmoid colon are discussed, and stress is laid on the importance of symptomatological, radiological and endoscopical examination, including biopsy. A description is given of the surgical criteria employed in 148 cases, with particular attention to the indications for anterior resection of the rectum and abdominoperineal amputation of the rectum according to Miles.", "contents": "[Criteria of surgical treatment in 148 cases of recto-sigmoid cancer]. The clinical aspects of cancer of the rectum and sigmoid colon are discussed, and stress is laid on the importance of symptomatological, radiological and endoscopical examination, including biopsy. A description is given of the surgical criteria employed in 148 cases, with particular attention to the indications for anterior resection of the rectum and abdominoperineal amputation of the rectum according to Miles."}
{"id": "PMID:224353", "title": "Genital Chlamydia trachomatis infections in patients with cervical atypia.", "content": "Of 177 gynecologic outpatients with cervical dysplasia studied, 29 (16%) were found to excrete Chlamydia trachomatis from their urogenital tract. Sera collected from 93 of these patients were significantly more often positive for and showed higher levels of antichlamydial micro-complement fixation (CF) and immunofluorescence (IF) antibodies than sera obtained from the controls. However, when the sera were tested for anti-herpesvirus type II (HSV-II) and cytomegalovirus (CMV) antibodies, no difference between the cases and the controls were encountered.", "contents": "Genital Chlamydia trachomatis infections in patients with cervical atypia. Of 177 gynecologic outpatients with cervical dysplasia studied, 29 (16%) were found to excrete Chlamydia trachomatis from their urogenital tract. Sera collected from 93 of these patients were significantly more often positive for and showed higher levels of antichlamydial micro-complement fixation (CF) and immunofluorescence (IF) antibodies than sera obtained from the controls. However, when the sera were tested for anti-herpesvirus type II (HSV-II) and cytomegalovirus (CMV) antibodies, no difference between the cases and the controls were encountered."}
{"id": "PMID:224354", "title": "Premature menopause: a reversible entity?", "content": "Secondary hypergonadotropic, hypoestrogenic amenorrhea, or premature menopause, is usually considered an irreversible process. Four patients with this entity were observed to have evidence of ovulation. Three of these patients became pregnant while they were treated with estrogen replacement therapy (ERT) for their hypoestrogenic symptoms. Estrogen replacement may be effective in reversal of this process.", "contents": "Premature menopause: a reversible entity? Secondary hypergonadotropic, hypoestrogenic amenorrhea, or premature menopause, is usually considered an irreversible process. Four patients with this entity were observed to have evidence of ovulation. Three of these patients became pregnant while they were treated with estrogen replacement therapy (ERT) for their hypoestrogenic symptoms. Estrogen replacement may be effective in reversal of this process."}
{"id": "PMID:224356", "title": "Cell-mediated immunity in patients with cervical cancer.", "content": "In 16 patients with cervical carcinoma (stages II and III) tumor-specific and general immune reactivity was investigated. Cancer patients' skin reactivity was different from that of controls insofar as there was a decreased response to streptokinase-streptodornase as well as to DNCB. Absence of DNCB sensitization was mainly in stage III patients. Cell-mediated immunity to autologous and/or allogeneic tumor-associated antigens (TAA) was demonstrated in vivo and in vitro. 3 of 8 patients had positive skin reactions to autologous TAA and 8 of 14 reacted to allogeneic TAA. In the lymphocyte migration inhibition test, 8 of 14 patients reacted to autologous tumor membrane preparations and 3 of 10 to allogeneic pooled preparations. In addition, there was some indication of cross-reaction with antigens from a human squamous cell carcinoma of the lung. There was no reaction in vitro to normal cervical tissue and no association between tumor-specific reactions and herpes simplex virus type II antibodies could be demonstrated. Patients with DNCB sensitization and in vivo as well as in vitro lymphocyte reactivity to TAA had a better prognosis than nonreacting patients, indicating the value of combined immunological tests.", "contents": "Cell-mediated immunity in patients with cervical cancer. In 16 patients with cervical carcinoma (stages II and III) tumor-specific and general immune reactivity was investigated. Cancer patients' skin reactivity was different from that of controls insofar as there was a decreased response to streptokinase-streptodornase as well as to DNCB. Absence of DNCB sensitization was mainly in stage III patients. Cell-mediated immunity to autologous and/or allogeneic tumor-associated antigens (TAA) was demonstrated in vivo and in vitro. 3 of 8 patients had positive skin reactions to autologous TAA and 8 of 14 reacted to allogeneic TAA. In the lymphocyte migration inhibition test, 8 of 14 patients reacted to autologous tumor membrane preparations and 3 of 10 to allogeneic pooled preparations. In addition, there was some indication of cross-reaction with antigens from a human squamous cell carcinoma of the lung. There was no reaction in vitro to normal cervical tissue and no association between tumor-specific reactions and herpes simplex virus type II antibodies could be demonstrated. Patients with DNCB sensitization and in vivo as well as in vitro lymphocyte reactivity to TAA had a better prognosis than nonreacting patients, indicating the value of combined immunological tests."}
{"id": "PMID:224357", "title": "Lymphocyte subpopulation in primary lung cancer.", "content": "To determine whether impaired cellular immune responsiveness in lung cancer patients is related to a reduction in the number of T lymphocytes, circulating levels of T-rosette-forming lymphocytes were measured in 48 cases with primary lung cancer and compared to levels in 94 age-matched healthy subjects. The results show that T lymphocytes levels are significantly reduced in lung cancer patients. A possible consequence of reduced numbers of circulating T lymphocytes would be a diminution in tumor-inhibiting (T-cell) influences and a corresponding relative enhancement of blocking (B-cell) influences, a circumstance which would favor tumor proliferation.", "contents": "Lymphocyte subpopulation in primary lung cancer. To determine whether impaired cellular immune responsiveness in lung cancer patients is related to a reduction in the number of T lymphocytes, circulating levels of T-rosette-forming lymphocytes were measured in 48 cases with primary lung cancer and compared to levels in 94 age-matched healthy subjects. The results show that T lymphocytes levels are significantly reduced in lung cancer patients. A possible consequence of reduced numbers of circulating T lymphocytes would be a diminution in tumor-inhibiting (T-cell) influences and a corresponding relative enhancement of blocking (B-cell) influences, a circumstance which would favor tumor proliferation."}
{"id": "PMID:224362", "title": "Infectious mononucleosis.", "content": "An up-to-date review of the clinical diagnostic and treatment of infectious mononucleosis, emphasizing on new etiological concepts (Epstein-Barr virus) and pathogenetic (T and B lymphocytes) interaction is presented.", "contents": "Infectious mononucleosis. An up-to-date review of the clinical diagnostic and treatment of infectious mononucleosis, emphasizing on new etiological concepts (Epstein-Barr virus) and pathogenetic (T and B lymphocytes) interaction is presented."}
{"id": "PMID:224363", "title": "Diagnosis and treatment of pertussis.", "content": "A review of the diagnostic methods of pertussis (clinical, radiological, laboratoryy: 42 case reports in a period of 2 1/2 years, being all hospitalized children with pertussis, aged from 23 days to 7 years. A review of the treatment with hyperimmune globulin, antibiotics, symptomatic treatment, and the results obtained, is presented.", "contents": "Diagnosis and treatment of pertussis. A review of the diagnostic methods of pertussis (clinical, radiological, laboratoryy: 42 case reports in a period of 2 1/2 years, being all hospitalized children with pertussis, aged from 23 days to 7 years. A review of the treatment with hyperimmune globulin, antibiotics, symptomatic treatment, and the results obtained, is presented."}
{"id": "PMID:224365", "title": "Ultrastructure of cardiovascular lesions induced by hypervitaminosis D and its withdrawal.", "content": "Aortic, coronary and cardiac lesions were induced in swine by a hypervitaminosis D3 diet Lipid-free intimal plaques overlying focally calcified medial or internal elastica occured in the thoracic aorta, pulmonary trunk and coronary artery of swine fed a basal ration supplemented with 250,000 IU of vitamin D3/kg of diet for an induction period of 4 months. Cartilage formation with minimal calcification was initiated in the aortic valve during this period. When such animals were subsequently fed only the basal ration free of excessive vitamin D3 for 3 months, intimal plaques regressed in the aorta and pulmonary trunk but progressed in the coronary artery. The calcific deposits in the medial elastica and internal elastica of all three arteries decreased in size. Atherosclerotic intimal thickening occurred in the main coronary arteries. The most severe lesion occupied 75 p.100 of the lumen area. Multiple intimal plaques were noted in the left atrium and aortic and mitral valves. The thickened intima at these coronary and cardiac sites contained calcified elastica and collagen fibers.", "contents": "Ultrastructure of cardiovascular lesions induced by hypervitaminosis D and its withdrawal. Aortic, coronary and cardiac lesions were induced in swine by a hypervitaminosis D3 diet Lipid-free intimal plaques overlying focally calcified medial or internal elastica occured in the thoracic aorta, pulmonary trunk and coronary artery of swine fed a basal ration supplemented with 250,000 IU of vitamin D3/kg of diet for an induction period of 4 months. Cartilage formation with minimal calcification was initiated in the aortic valve during this period. When such animals were subsequently fed only the basal ration free of excessive vitamin D3 for 3 months, intimal plaques regressed in the aorta and pulmonary trunk but progressed in the coronary artery. The calcific deposits in the medial elastica and internal elastica of all three arteries decreased in size. Atherosclerotic intimal thickening occurred in the main coronary arteries. The most severe lesion occupied 75 p.100 of the lumen area. Multiple intimal plaques were noted in the left atrium and aortic and mitral valves. The thickened intima at these coronary and cardiac sites contained calcified elastica and collagen fibers."}
{"id": "PMID:224361", "title": "Immunovirologic assessment of American patients with nasopharyngeal carcinoma and occult primary tumors.", "content": "The Epstein-Barr virus (EBV) is closely associated with nasopharyngeal carcinoma, suggesting an etiologic relationship. We have under-taken studies (1) to quantitate the relationship between antibody titers to EBV-associated antigens and nasopharyngeal carcinoma in American patients since most of the patients in previous studies were of either Asian or African descent and (2) to determine the relationship between antibody titers and the clinical course of the disease. Sera from patients with primary or recurrent nasopharyngeal carcinoma and from patients in remission, from patients with various other head and neck tumors (including occult primary lesions and lymphomas), and from normal controls were titrated for IgG antibodies to viral capsid antigen (VCA) and early antigen and IgA antibodies to VCA, using indirect immunofluorescence procedures previously detailed. High titers of antibodies to EBV-induced early antigens and VCA in the IgG fraction and VCA in the IgA fraction were frequently found in the sera of patients with nasopharyngeal carcinoma. A significant reduction in these titers was observed with clinical remission of the disease in treated patients. Preliminary findings suggest that EBV serology may be useful in the evaluation and treatment of patients with nasopharyngeal carcinoma and also in patients with cervical metastases from clinically occult promary sites in order to identify those with occult nasopharyngeal carcinoma.", "contents": "Immunovirologic assessment of American patients with nasopharyngeal carcinoma and occult primary tumors. The Epstein-Barr virus (EBV) is closely associated with nasopharyngeal carcinoma, suggesting an etiologic relationship. We have under-taken studies (1) to quantitate the relationship between antibody titers to EBV-associated antigens and nasopharyngeal carcinoma in American patients since most of the patients in previous studies were of either Asian or African descent and (2) to determine the relationship between antibody titers and the clinical course of the disease. Sera from patients with primary or recurrent nasopharyngeal carcinoma and from patients in remission, from patients with various other head and neck tumors (including occult primary lesions and lymphomas), and from normal controls were titrated for IgG antibodies to viral capsid antigen (VCA) and early antigen and IgA antibodies to VCA, using indirect immunofluorescence procedures previously detailed. High titers of antibodies to EBV-induced early antigens and VCA in the IgG fraction and VCA in the IgA fraction were frequently found in the sera of patients with nasopharyngeal carcinoma. A significant reduction in these titers was observed with clinical remission of the disease in treated patients. Preliminary findings suggest that EBV serology may be useful in the evaluation and treatment of patients with nasopharyngeal carcinoma and also in patients with cervical metastases from clinically occult promary sites in order to identify those with occult nasopharyngeal carcinoma."}
{"id": "PMID:224372", "title": "Plasma cyclic nucleotide determination in the investigation of hypocalcemia.", "content": "Changes in plasma adenosine 3'5' (cAMP) and guanosine (cGMP) monophosphate, measured by specific radioimmunoassay, after 150 USP/M2 of bovine parathyroid hormone (bPTH) iv administered were studied in children with pseudohypoparathyroidism, and idiopathic hypoparathyroidism, and in normal controls. Basal concentrations of plasma cAMP (17 nmole/1 +/- 1, 6 SEM) and cGMP (8,7 nmole/1 +/- 1, 3 SEM) were the same in all studied children. Plasma cAMP in normal and idiopathic hypoparathyroid children significantly (30-fold, P less than 0.001) and constantly rose with a peak value (537 nmole/1 +/- 210 SEM) observed 5--10 min after bPTH injection. By contrast, no significant change in plasma cAMP occurred in children with pseudohypoparathyroidism. The data confirmed further the unability of pseudohypoparathyroid children to increase cAMP after exogenous PTH, while the cGMP response did not appear to be significantly modified. It is suggested that an injection of 150 USP/m2 bPTH with plasma samples for cAMP assay taken before and 10 min after hormone administration represents a simplified assessment of Ellsworth-Howard's test.", "contents": "Plasma cyclic nucleotide determination in the investigation of hypocalcemia. Changes in plasma adenosine 3'5' (cAMP) and guanosine (cGMP) monophosphate, measured by specific radioimmunoassay, after 150 USP/M2 of bovine parathyroid hormone (bPTH) iv administered were studied in children with pseudohypoparathyroidism, and idiopathic hypoparathyroidism, and in normal controls. Basal concentrations of plasma cAMP (17 nmole/1 +/- 1, 6 SEM) and cGMP (8,7 nmole/1 +/- 1, 3 SEM) were the same in all studied children. Plasma cAMP in normal and idiopathic hypoparathyroid children significantly (30-fold, P less than 0.001) and constantly rose with a peak value (537 nmole/1 +/- 210 SEM) observed 5--10 min after bPTH injection. By contrast, no significant change in plasma cAMP occurred in children with pseudohypoparathyroidism. The data confirmed further the unability of pseudohypoparathyroid children to increase cAMP after exogenous PTH, while the cGMP response did not appear to be significantly modified. It is suggested that an injection of 150 USP/m2 bPTH with plasma samples for cAMP assay taken before and 10 min after hormone administration represents a simplified assessment of Ellsworth-Howard's test."}
{"id": "PMID:224378", "title": "[Vasoactive intestinal peptide (VIP) in the Verner-Morrison syndrome (author's transl)].", "content": "An early diagnosis of the Verner-Morrison syndrome will greatly enhance the chances of curative resection. There is a striking need for a simple diagnostic test. A number of suggestions have been made for the presumed hormone mediator of this syndrome. Numerous reports have led to a wide acceptance that vasoactive intestinal peptide (VIP) is the responsible mediator for the pharmacologic actions of this peptide are similar to the physiological characteristics noted in the watery diarrhea syndrome. A raised plasma VIP concentration, on the other hand, would suggest the presence of a tumour. These observations argue for the radioimmunoassay measurement of plasma VIP in a patient with the watery diarrhea syndrome.", "contents": "[Vasoactive intestinal peptide (VIP) in the Verner-Morrison syndrome (author's transl)]. An early diagnosis of the Verner-Morrison syndrome will greatly enhance the chances of curative resection. There is a striking need for a simple diagnostic test. A number of suggestions have been made for the presumed hormone mediator of this syndrome. Numerous reports have led to a wide acceptance that vasoactive intestinal peptide (VIP) is the responsible mediator for the pharmacologic actions of this peptide are similar to the physiological characteristics noted in the watery diarrhea syndrome. A raised plasma VIP concentration, on the other hand, would suggest the presence of a tumour. These observations argue for the radioimmunoassay measurement of plasma VIP in a patient with the watery diarrhea syndrome."}
{"id": "PMID:224381", "title": "Mobile gamma cameras and 99mTc-labelled phosphates in acute myocardial infarction.", "content": "99mTc-labelled phosphates (PyP, IDP and MDP) were compared for their usefulness for the diagnosis of myocardial infarction. The results indicated the superiority of 99mTc-labelled imidodiphosphonate over the other 99mTc-labelled phosphates. At the same time, two mobile gamma cameras were compared with respect to their instrumental characteristics and clinical versalitity and their advantages and disadvantages are reported.", "contents": "Mobile gamma cameras and 99mTc-labelled phosphates in acute myocardial infarction. 99mTc-labelled phosphates (PyP, IDP and MDP) were compared for their usefulness for the diagnosis of myocardial infarction. The results indicated the superiority of 99mTc-labelled imidodiphosphonate over the other 99mTc-labelled phosphates. At the same time, two mobile gamma cameras were compared with respect to their instrumental characteristics and clinical versalitity and their advantages and disadvantages are reported."}
{"id": "PMID:224385", "title": "Diagnostic aspects of the cytomegalovirus mononucleosis syndrome in previously healthy persons.", "content": "The mononucleosis-like syndrome due to cytomegalovirus (CMV) has many clinical features in common with classic Epstein-Barr virus (EBV) induced infectious mononucleosis (IM). The hematologic and hepatic findings in both diseases are identical. Diagnosis of the CMV-IM syndrome usually can be made on the basis of indirect immunofluorescence for CMV macroglobulins (CMV-IgM). EBV virologic tests may also be necessary, as patients with primary EBV infections may have cross-reactions at low titer in the CMV-IgM test.", "contents": "Diagnostic aspects of the cytomegalovirus mononucleosis syndrome in previously healthy persons. The mononucleosis-like syndrome due to cytomegalovirus (CMV) has many clinical features in common with classic Epstein-Barr virus (EBV) induced infectious mononucleosis (IM). The hematologic and hepatic findings in both diseases are identical. Diagnosis of the CMV-IM syndrome usually can be made on the basis of indirect immunofluorescence for CMV macroglobulins (CMV-IgM). EBV virologic tests may also be necessary, as patients with primary EBV infections may have cross-reactions at low titer in the CMV-IgM test."}
{"id": "PMID:224386", "title": "Accumulation of 125I in the oocytes, thyroids, and plasma of laying Japanese quail treated with cyclic AMP, theophylline, or prostaglandins E1 or E2.", "content": "Dibutyryl cyclic AMP, theophyline, or prostaglandins E1 or E2 were injected intraperitoneally into laying Japanese quail in an attempt to stimulate increased transference of iodide by the ovarian membranes. Theophyline induced increased 18-hr 125I accumulations (by 7 to 18% of the injected dose) of borderline significance in the growing oocytes of some test groups. Theophyline plus DBcAMP treatment lead to a slight increase in 125I accumulation in the thyroid. Other treatments had no apparent effect on 125I transference. The prostaglandins induced oviposition within minutes of injection, as has been reported for uterine application of prostaglandins by other investigators. Means for plasma 125I levels for treated quail were 1.7 to 12.5 times greater than control levels. Values for oocyte to plasma and thyroid to plasma 125I ratios, it appeared that DBcAMP, theophyline, and the prostaglandins inhibited rather than stimulated the accumulation of 125I by the ovary and thyroid of the quail.", "contents": "Accumulation of 125I in the oocytes, thyroids, and plasma of laying Japanese quail treated with cyclic AMP, theophylline, or prostaglandins E1 or E2. Dibutyryl cyclic AMP, theophyline, or prostaglandins E1 or E2 were injected intraperitoneally into laying Japanese quail in an attempt to stimulate increased transference of iodide by the ovarian membranes. Theophyline induced increased 18-hr 125I accumulations (by 7 to 18% of the injected dose) of borderline significance in the growing oocytes of some test groups. Theophyline plus DBcAMP treatment lead to a slight increase in 125I accumulation in the thyroid. Other treatments had no apparent effect on 125I transference. The prostaglandins induced oviposition within minutes of injection, as has been reported for uterine application of prostaglandins by other investigators. Means for plasma 125I levels for treated quail were 1.7 to 12.5 times greater than control levels. Values for oocyte to plasma and thyroid to plasma 125I ratios, it appeared that DBcAMP, theophyline, and the prostaglandins inhibited rather than stimulated the accumulation of 125I by the ovary and thyroid of the quail."}
{"id": "PMID:224387", "title": "Validation of an in vitro method for incorporating labelled cholesterol into human erythrocytes.", "content": "At least 85% of the cholesterol of human erythrocytes can be replaced by isotopically labelled cholesterol, by incubation of the cells with the plasma lipoprotein HDL3 into which labelled cholesterol has been incorporated from Celite. With erythrocytes containing 40% labelled cholesterol, the reactivity of the incorporated labelled cholesterol was the same as that of the remaining native cholesterol with regard to: oxidation by cholesterol oxidase for both intact erythrocytes and cell ghosts, extraction by cholesterol depleted plasma, and exchange for HDL3 cholesterol. Also, the reactivity of the cholesterol in the cells in which labelled cholesterol was incorporated was the same as in untreated erythrocytes.", "contents": "Validation of an in vitro method for incorporating labelled cholesterol into human erythrocytes. At least 85% of the cholesterol of human erythrocytes can be replaced by isotopically labelled cholesterol, by incubation of the cells with the plasma lipoprotein HDL3 into which labelled cholesterol has been incorporated from Celite. With erythrocytes containing 40% labelled cholesterol, the reactivity of the incorporated labelled cholesterol was the same as that of the remaining native cholesterol with regard to: oxidation by cholesterol oxidase for both intact erythrocytes and cell ghosts, extraction by cholesterol depleted plasma, and exchange for HDL3 cholesterol. Also, the reactivity of the cholesterol in the cells in which labelled cholesterol was incorporated was the same as in untreated erythrocytes."}
{"id": "PMID:224389", "title": "[Clinical value of radionuclide imaging in the diagnosis of the adrenal cortex lesions].", "content": "Results of using radioisotopic visualization of the adrenal glands together with the hormonal profile determination ACTH, renin, aldosterone, cortisol) for the diagnosis of the adrenal gland affections are presented. Parameters of the scintigraphic appearance of the affected adrenal cortex were developed to distinguish six types of scintigraphic patterns of the adrenal gland, which were the most frequent. Clinical analysis of the results of the examination of patients indicated Conn's disease in 24 patients (it was verified during the operation), 12 had unilateral corticosteroma of the adrenal gland, 8 suffered from residual adrenal gland tissue, and 2 had metastases of malignant tumours of the adrenal glands. Accumulation of radiopharmaceutical preparations into the corpus luteum was revealed in one case.", "contents": "[Clinical value of radionuclide imaging in the diagnosis of the adrenal cortex lesions]. Results of using radioisotopic visualization of the adrenal glands together with the hormonal profile determination ACTH, renin, aldosterone, cortisol) for the diagnosis of the adrenal gland affections are presented. Parameters of the scintigraphic appearance of the affected adrenal cortex were developed to distinguish six types of scintigraphic patterns of the adrenal gland, which were the most frequent. Clinical analysis of the results of the examination of patients indicated Conn's disease in 24 patients (it was verified during the operation), 12 had unilateral corticosteroma of the adrenal gland, 8 suffered from residual adrenal gland tissue, and 2 had metastases of malignant tumours of the adrenal glands. Accumulation of radiopharmaceutical preparations into the corpus luteum was revealed in one case."}
{"id": "PMID:224390", "title": "[Participation of different parts of the tonsils and the hippocampus in the regulation of the pituitary-adrenal cortex system in rats].", "content": "In experiments on rats the effect of electric coagulation of the tonsil and hippocamp on the functional activity of the pituitary-adrenal axis was studied. The weight of the adenohypophysis after the coagulation of the medial or lateral tonsils proved to decrease; the ACTH content in the hypophysis and the cortocosteroid level in the peripheral blood plasma diminished, and the compensatory hypertrophy of the remaining adrenal gland was intensified in rats with destroyed medial tonsil. The dorsal hippocamp coagulation was accompanied by a decrease in the adenohypophysis ACTH content, and the ventral hippocamp destruction led to reduction of corticosteroid secretion into the adrenal vein; in both cases the reaction to the irritation was potentiated. It was concluded that different parts of the tonsil and hippocamp influenced the pituitary-adrenal function unequally.", "contents": "[Participation of different parts of the tonsils and the hippocampus in the regulation of the pituitary-adrenal cortex system in rats]. In experiments on rats the effect of electric coagulation of the tonsil and hippocamp on the functional activity of the pituitary-adrenal axis was studied. The weight of the adenohypophysis after the coagulation of the medial or lateral tonsils proved to decrease; the ACTH content in the hypophysis and the cortocosteroid level in the peripheral blood plasma diminished, and the compensatory hypertrophy of the remaining adrenal gland was intensified in rats with destroyed medial tonsil. The dorsal hippocamp coagulation was accompanied by a decrease in the adenohypophysis ACTH content, and the ventral hippocamp destruction led to reduction of corticosteroid secretion into the adrenal vein; in both cases the reaction to the irritation was potentiated. It was concluded that different parts of the tonsil and hippocamp influenced the pituitary-adrenal function unequally."}
{"id": "PMID:224391", "title": "[Study of the somatotropic function of the pituitary gland and the glucocorticoid function of the adrenal glands in rats with alloxan diabetes].", "content": "The somatotropichormone (STH) content was studied in the hypophysis and the peripheral blood of rats with alloxan diabetes; the corticosterone content was determined in their peripheral blood. The STH content in the peripheral blood and the hypophysis of these rats failed to differ from that in the control group, but the blood STH content rose considerably in the sick animals. Exclusion of the insular apparatus function was accompanied by the adrenal gland hypertrophy, which correlated with the rise of the blood corticosterone level. The data obtained indicated that the insular apparatus insufficiency induced by alloxan was accompanied by changes in the somatotropic function of the hypophysis and of glucocorticoid function of the adrenal glands.", "contents": "[Study of the somatotropic function of the pituitary gland and the glucocorticoid function of the adrenal glands in rats with alloxan diabetes]. The somatotropichormone (STH) content was studied in the hypophysis and the peripheral blood of rats with alloxan diabetes; the corticosterone content was determined in their peripheral blood. The STH content in the peripheral blood and the hypophysis of these rats failed to differ from that in the control group, but the blood STH content rose considerably in the sick animals. Exclusion of the insular apparatus function was accompanied by the adrenal gland hypertrophy, which correlated with the rise of the blood corticosterone level. The data obtained indicated that the insular apparatus insufficiency induced by alloxan was accompanied by changes in the somatotropic function of the hypophysis and of glucocorticoid function of the adrenal glands."}
{"id": "PMID:224404", "title": "Emotional disturbance following childbirth: clinical findings and urinary excretion of cyclic AMP (adenosine 3'5'cyclic monophosphate).", "content": "Emotional disturbance was assessed in a group of women in the first few days following childbirth and again 2 months and 1 year following childbirth; the clinical features are described. Variables such as social class, age and parity were not related to the level of emotional disturbance, but a history of marital problems, sexual difficulties, poor relationships with immediate family or disrupted family relationships in childhood were so related. Twenty-four hour urinary excretion of cyclic AMP (adenosine 3'5' cyclic monophosphate) was estimated in the same group of women on 2 occasions in the week following childbirth and again 2-3 months later in approximately one third of the original sample. Excretion of cyclic AMP in the few days following delivery was elevated compared with excretion 2-3 months later, and there was a significant rise in urinary excretion of cyclic AMP between the 1st and 2nd urine collections. Those women showing most emotional disturbance on the 3rd day after delivery and women indicating most mood change in the direction of becoming elated had the highest levels of cyclic AMP in the 2nd urine collection.", "contents": "Emotional disturbance following childbirth: clinical findings and urinary excretion of cyclic AMP (adenosine 3'5'cyclic monophosphate). Emotional disturbance was assessed in a group of women in the first few days following childbirth and again 2 months and 1 year following childbirth; the clinical features are described. Variables such as social class, age and parity were not related to the level of emotional disturbance, but a history of marital problems, sexual difficulties, poor relationships with immediate family or disrupted family relationships in childhood were so related. Twenty-four hour urinary excretion of cyclic AMP (adenosine 3'5' cyclic monophosphate) was estimated in the same group of women on 2 occasions in the week following childbirth and again 2-3 months later in approximately one third of the original sample. Excretion of cyclic AMP in the few days following delivery was elevated compared with excretion 2-3 months later, and there was a significant rise in urinary excretion of cyclic AMP between the 1st and 2nd urine collections. Those women showing most emotional disturbance on the 3rd day after delivery and women indicating most mood change in the direction of becoming elated had the highest levels of cyclic AMP in the 2nd urine collection."}
{"id": "PMID:224407", "title": "Influence of the DNA structure on the free radical induction due to proflavine and light treatment.", "content": "Induction of peroxide free radicals (detected by Electron Paramagnetic Resonance at 77 K) due to the photodynamic activity of proflavine was measured on bacteriophage phi X174 DNA either single-stranded (ss) as isolated from the virion, or double-stranded supercoiled (RFI) as isolated from the infected bacteria. Comparison was made with calf thymus DNA photosensitization. In order to use equivalent DNA-proflavine complexes, binding of the dye to the three DNA's was first determined under those conditions of high ionic strength favourable to the photodynamic reaction. Free radical induction was maximal for definite amounts of bound proflavine (which varied depending upon the DNA substrate) and at an ionic strength value of 0.5. The level of the maximal reaction increased in the following order: from phi Xss DNA to calf thymus DNA and finally to phi XRFI DNA. The conformation of the proflavine-DNA complex was thus a determinant for the efficiency of the photodynamic process. The ionic strength effect could not be explained by the evolution of the proflavine triplet state in irradiated proflavine-calf thymus DNA complexes.", "contents": "Influence of the DNA structure on the free radical induction due to proflavine and light treatment. Induction of peroxide free radicals (detected by Electron Paramagnetic Resonance at 77 K) due to the photodynamic activity of proflavine was measured on bacteriophage phi X174 DNA either single-stranded (ss) as isolated from the virion, or double-stranded supercoiled (RFI) as isolated from the infected bacteria. Comparison was made with calf thymus DNA photosensitization. In order to use equivalent DNA-proflavine complexes, binding of the dye to the three DNA's was first determined under those conditions of high ionic strength favourable to the photodynamic reaction. Free radical induction was maximal for definite amounts of bound proflavine (which varied depending upon the DNA substrate) and at an ionic strength value of 0.5. The level of the maximal reaction increased in the following order: from phi Xss DNA to calf thymus DNA and finally to phi XRFI DNA. The conformation of the proflavine-DNA complex was thus a determinant for the efficiency of the photodynamic process. The ionic strength effect could not be explained by the evolution of the proflavine triplet state in irradiated proflavine-calf thymus DNA complexes."}
{"id": "PMID:224413", "title": "Pharmacodynamics of stannous chelates administered with 99mTc-labeled chelates.", "content": "The pharmacodynamics of several tin compounds were studied in healthy rabbits, rabbits with myocardial infarcts, and isolated myocardial tissue. The results showed that tin chelates of pyrophosphate, HEDP, DTPA, and glucoheptonate are very unstable in vivo, giving rise to free stannous ions. These ions localize mainly in bone, with the rest being primarily excreted in the urine. They also concentrate more in infarcted than in normal myocardium; there they enter the mitochondria. The supernatant of homogenates contains bound and free fractions, demonstrating a subcellular distribution pattern similar to that of calcium ions. Tin chelates have different pharmacodynamics from the corresponding 99mTc chelates.", "contents": "Pharmacodynamics of stannous chelates administered with 99mTc-labeled chelates. The pharmacodynamics of several tin compounds were studied in healthy rabbits, rabbits with myocardial infarcts, and isolated myocardial tissue. The results showed that tin chelates of pyrophosphate, HEDP, DTPA, and glucoheptonate are very unstable in vivo, giving rise to free stannous ions. These ions localize mainly in bone, with the rest being primarily excreted in the urine. They also concentrate more in infarcted than in normal myocardium; there they enter the mitochondria. The supernatant of homogenates contains bound and free fractions, demonstrating a subcellular distribution pattern similar to that of calcium ions. Tin chelates have different pharmacodynamics from the corresponding 99mTc chelates."}
{"id": "PMID:224414", "title": "Enhancement of tissue structure visualization in breast specimen radiography.", "content": "A simple technique is described for producing enhanced radiographs of excised breast specimens with clinical mammographic equipment. Radiographs of specimens immersed in water are compared to radiographs of the same specimen in air. Using this fluid-balancing technique, visualization of tissue structure is enhanced, particularly when negative-mode Xerox or film is used.", "contents": "Enhancement of tissue structure visualization in breast specimen radiography. A simple technique is described for producing enhanced radiographs of excised breast specimens with clinical mammographic equipment. Radiographs of specimens immersed in water are compared to radiographs of the same specimen in air. Using this fluid-balancing technique, visualization of tissue structure is enhanced, particularly when negative-mode Xerox or film is used."}
{"id": "PMID:224415", "title": "A multihole catheter for maintaining longterm percutaneous antegrade biliary drainage.", "content": "The use of multihole catheters to achieve longterm antegrade biliary drainage in 43 patients with obstructive jaundice is described. Catheters were positioned with sideholes both above and below an obstruction and continued patency maintained. Better results were obtained using larger diameters and larger sideholes.", "contents": "A multihole catheter for maintaining longterm percutaneous antegrade biliary drainage. The use of multihole catheters to achieve longterm antegrade biliary drainage in 43 patients with obstructive jaundice is described. Catheters were positioned with sideholes both above and below an obstruction and continued patency maintained. Better results were obtained using larger diameters and larger sideholes."}
{"id": "PMID:224416", "title": "Pyrophosphate retention by previously irradiated renal tissue.", "content": "In 3 patients, each of whom had previously had part of one kidney included within the field during radiation therapy, whole-body bone imaging using 99mTc-pyrophosphate showed increased activity in the irradiated renal segment. Possible mechanisms of such renal uptake are discussed.", "contents": "Pyrophosphate retention by previously irradiated renal tissue. In 3 patients, each of whom had previously had part of one kidney included within the field during radiation therapy, whole-body bone imaging using 99mTc-pyrophosphate showed increased activity in the irradiated renal segment. Possible mechanisms of such renal uptake are discussed."}
{"id": "PMID:224417", "title": "Comparison of radiopaque perfluorocarbon and Ethiodol in lymphography.", "content": "Lymphangiography was performed on 40 adult cats, 39 dogs, 20 rabbits, and 12 rats of mixed sex using Ethiodol or radiopaque perfluorocarbon (BPC). Ethiodol was more radiodense than RPC, but imaging of lymph channels and nodes was satisfactory with the latter. RPC could be infused rapidly, while Ethiodol infusion was time consuming. RPC was biologically inert; Ethiodol produced both local and systemic inflammatory reactions. The lymph node distribution with RPC was more uniform and persisted for longer periods. It was concluded that RPC was an improvement over Ethiodol for lymphangiography.", "contents": "Comparison of radiopaque perfluorocarbon and Ethiodol in lymphography. Lymphangiography was performed on 40 adult cats, 39 dogs, 20 rabbits, and 12 rats of mixed sex using Ethiodol or radiopaque perfluorocarbon (BPC). Ethiodol was more radiodense than RPC, but imaging of lymph channels and nodes was satisfactory with the latter. RPC could be infused rapidly, while Ethiodol infusion was time consuming. RPC was biologically inert; Ethiodol produced both local and systemic inflammatory reactions. The lymph node distribution with RPC was more uniform and persisted for longer periods. It was concluded that RPC was an improvement over Ethiodol for lymphangiography."}
{"id": "PMID:224420", "title": "Effect of prostaglandins on cyclic nucleotide levels in cultured keratinocytes.", "content": "Ginea pig ear epidermal cells (keratinocytes) were established in primary cultures using trypsin, and treated in their proliferative phase of growth with prostaglandins E1, D1, F1 alpha, E2, D2, or F2 alpha. This phase is induced by the addition of retinoic acid during cell plating. Intracellular content of cAMP and cGMP was measured by radioimmunoassay at various times after treatment. Maximum stimulation of cAMP levels was observed with PGD2, smaller increases with PGE2 and relatively transient rises with PGF2 alpha which were of low significance, but confirm earlier data. Similar results were observed with PGD1, PGE1, and PGF1 alpha with smaller increases. The effects of D and E PGs were biphasic. Significant increases in cGMP were immediately observed with PGD2 and PGE2. With PGF2 alpha, maximum cGMP levels were noted after some delay. All PGs tested showed some effect in elevating cyclic nucleotides in keratinocytes. The most striking result was the increase in cAMP on PGD2 treatment.", "contents": "Effect of prostaglandins on cyclic nucleotide levels in cultured keratinocytes. Ginea pig ear epidermal cells (keratinocytes) were established in primary cultures using trypsin, and treated in their proliferative phase of growth with prostaglandins E1, D1, F1 alpha, E2, D2, or F2 alpha. This phase is induced by the addition of retinoic acid during cell plating. Intracellular content of cAMP and cGMP was measured by radioimmunoassay at various times after treatment. Maximum stimulation of cAMP levels was observed with PGD2, smaller increases with PGE2 and relatively transient rises with PGF2 alpha which were of low significance, but confirm earlier data. Similar results were observed with PGD1, PGE1, and PGF1 alpha with smaller increases. The effects of D and E PGs were biphasic. Significant increases in cGMP were immediately observed with PGD2 and PGE2. With PGF2 alpha, maximum cGMP levels were noted after some delay. All PGs tested showed some effect in elevating cyclic nucleotides in keratinocytes. The most striking result was the increase in cAMP on PGD2 treatment."}
{"id": "PMID:224421", "title": "[Recurrences of the gastric carcinoma after surgery (author's transl)].", "content": "A series of 71 patients with recurrences of gastric carcinoma after operation is reviewed. The most frequent localization is the gastric bed (48 cases , 67.6%) while the local recurrences is less frequent (22 cases, 30.9%) and usually the esophago-cardial junction is affected. In one patient both the local recurrence and that of the gastric bed were present. The radiologic investigation was negative in about 60% of the patients because it is not useful for a correct examination of the gastric bed. In any case it must be considered essential for the study of the local recurrences and for the evaluation of the post operative anatomic patterns.", "contents": "[Recurrences of the gastric carcinoma after surgery (author's transl)]. A series of 71 patients with recurrences of gastric carcinoma after operation is reviewed. The most frequent localization is the gastric bed (48 cases , 67.6%) while the local recurrences is less frequent (22 cases, 30.9%) and usually the esophago-cardial junction is affected. In one patient both the local recurrence and that of the gastric bed were present. The radiologic investigation was negative in about 60% of the patients because it is not useful for a correct examination of the gastric bed. In any case it must be considered essential for the study of the local recurrences and for the evaluation of the post operative anatomic patterns."}
{"id": "PMID:224422", "title": "[Comedocarcinoma of the breast: mammographic and thermographic evaluation of 52 cases (author's transl)].", "content": "A series of 52 patients with comedocarcinoma of the breast was studied by means of mammography and thermography. All the patients underwent surgery and histologic examination. The results stress the importance of these investigations which reach a diagnostic accuracy in 98% of the cases.", "contents": "[Comedocarcinoma of the breast: mammographic and thermographic evaluation of 52 cases (author's transl)]. A series of 52 patients with comedocarcinoma of the breast was studied by means of mammography and thermography. All the patients underwent surgery and histologic examination. The results stress the importance of these investigations which reach a diagnostic accuracy in 98% of the cases."}
{"id": "PMID:224423", "title": "[Lymphographic examinations in the pediatric age: review of 413 cases].", "content": "From January 1969-June 1978, 413 children less than 15 years of age underwent lymphography at the National Cancer Institute, Milan. Successful lymphatic cannulation was accomplished in 97.7% (769/787) of the sites where it was attempted. No major or permanent complications were encountered. In those children undergoing biopsy of opacified lymph nodes, lymphographic-histologic correlation was 94.5% (104/110). 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.", "contents": "[Lymphographic examinations in the pediatric age: review of 413 cases]. From January 1969-June 1978, 413 children less than 15 years of age underwent lymphography at the National Cancer Institute, Milan. Successful lymphatic cannulation was accomplished in 97.7% (769/787) of the sites where it was attempted. No major or permanent complications were encountered. In those children undergoing biopsy of opacified lymph nodes, lymphographic-histologic correlation was 94.5% (104/110). 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."}
{"id": "PMID:224424", "title": "[Hepatography in the course of lymphography].", "content": "Two cases are presented in which epatography occurred following lymphangiography. The morphologic findings and their changes in subsequent controls are described. Attention is pointed on the uncommon persistance of epatography for a few months from lymphangiography.", "contents": "[Hepatography in the course of lymphography]. Two cases are presented in which epatography occurred following lymphangiography. The morphologic findings and their changes in subsequent controls are described. Attention is pointed on the uncommon persistance of epatography for a few months from lymphangiography."}
{"id": "PMID:224433", "title": "Immunosuppression in bovine trypanosomiasis: studies with louping-ill vaccine.", "content": "The antibody response to louping-ill virus vaccine was examined in mice infected with Trypanosoma brucei and T congolense, and in Ethiopian cattle experimentally infected with T brucei, T congolense  and T vivax. In mice the antibody response was completely suppressed, while in cattle infected with T congolense and T vivax the antibody response to the vaccine was only 10 per cent that of uninfected animals. In contrast, the response of cattle infected with T brucei was not significantly reduced, and this was attributed to their relatively light and transient parasitaemias. Trypanocidal chemotherapy (diminazine aceturate) administered on the same day as vaccination largely restored the competence of the immune response of both mice and cattle infected with T congolense. The use of such drugs should be considered when cattle are vaccinated in trypanosome endemic areas.", "contents": "Immunosuppression in bovine trypanosomiasis: studies with louping-ill vaccine. The antibody response to louping-ill virus vaccine was examined in mice infected with Trypanosoma brucei and T congolense, and in Ethiopian cattle experimentally infected with T brucei, T congolense  and T vivax. In mice the antibody response was completely suppressed, while in cattle infected with T congolense and T vivax the antibody response to the vaccine was only 10 per cent that of uninfected animals. In contrast, the response of cattle infected with T brucei was not significantly reduced, and this was attributed to their relatively light and transient parasitaemias. Trypanocidal chemotherapy (diminazine aceturate) administered on the same day as vaccination largely restored the competence of the immune response of both mice and cattle infected with T congolense. The use of such drugs should be considered when cattle are vaccinated in trypanosome endemic areas."}
{"id": "PMID:224434", "title": "The effect of tetrathiomolybdate upon sheep caeruloplasmin amine oxidase activity in vitro: the influence of substrate on apparent sensitivity to inhibition.", "content": "The effect of molybdate, dithiomolybdate, tetrathiomolybdate and diethyldithiocarbamate on caeruloplasmin amine oxidase activity was examined using o-dianisidine as a substrate. Enzyme activity was strongly inhibited by tetrathiomolybdate (1.5 X 10(6)M), oxidation of another substrate, p-phenylenediamine, was inhibited only slightly.", "contents": "The effect of tetrathiomolybdate upon sheep caeruloplasmin amine oxidase activity in vitro: the influence of substrate on apparent sensitivity to inhibition. The effect of molybdate, dithiomolybdate, tetrathiomolybdate and diethyldithiocarbamate on caeruloplasmin amine oxidase activity was examined using o-dianisidine as a substrate. Enzyme activity was strongly inhibited by tetrathiomolybdate (1.5 X 10(6)M), oxidation of another substrate, p-phenylenediamine, was inhibited only slightly."}
{"id": "PMID:224435", "title": "The susceptibility of chicken kidney and oviduct organ cultures to a vaccine strain of avian infectious bronchitis virus.", "content": "The minimal infectious dose of the H52 strain of infectious bronchitis virus for organ cultures of oviduct and kidney was compared in chickens of different ages. Organ cultures of oviduct were found to be highly susceptible to infection regardless of the age of chicken and no difference in susceptibility could be demonstrated between cultures of the magnum and uterus regions of the mature oviduct. Kidney organ cultures were less susceptible and resistance to infection increased significantly (P less than 0.001) with the age of the chicken from which cultures were prepared.", "contents": "The susceptibility of chicken kidney and oviduct organ cultures to a vaccine strain of avian infectious bronchitis virus. The minimal infectious dose of the H52 strain of infectious bronchitis virus for organ cultures of oviduct and kidney was compared in chickens of different ages. Organ cultures of oviduct were found to be highly susceptible to infection regardless of the age of chicken and no difference in susceptibility could be demonstrated between cultures of the magnum and uterus regions of the mature oviduct. Kidney organ cultures were less susceptible and resistance to infection increased significantly (P less than 0.001) with the age of the chicken from which cultures were prepared."}
{"id": "PMID:224439", "title": "[Amyloid neuropathy associated with a benign monoclonal gammopathy (lambda light chains)].", "content": "The authors report a case of non-familial amyloid neuropathy in which there was sensory-motor neuropathy of the 4 limbs, multiple lesions in the cranial nerves, and large subcutaneous amyloid deposits. Biopsy samples showed the presence of amyloid deposits in the interstitial tissues, the vessel walls in the muscle hypodermis, and in the bone marrow. A light monoclonal lambda chain was present in the serum. Immunofluorescent studies of the biopsy specimens showed the presence of elective fluorescence with an anti-lambda immunoserum in the amyloid substance.", "contents": "[Amyloid neuropathy associated with a benign monoclonal gammopathy (lambda light chains)]. The authors report a case of non-familial amyloid neuropathy in which there was sensory-motor neuropathy of the 4 limbs, multiple lesions in the cranial nerves, and large subcutaneous amyloid deposits. Biopsy samples showed the presence of amyloid deposits in the interstitial tissues, the vessel walls in the muscle hypodermis, and in the bone marrow. A light monoclonal lambda chain was present in the serum. Immunofluorescent studies of the biopsy specimens showed the presence of elective fluorescence with an anti-lambda immunoserum in the amyloid substance."}
{"id": "PMID:224443", "title": "[Histological and ultrastructural features of a case of subacute sclerosing panencephalitis (author's transl)].", "content": "A case of subacute sclerosing panencephalitis is described from a clinical, histopathological and ultrastructural point of view. The most notable morphologic feature is the presence of a great number of nuclear inclusions inside both neurons and oligodendroglial cells. These inclusions are spread to the whole brain and are decreasing in number from the cerebral cortex towards midbrain. The cerebellum is completely spared. The Authors discuss the problems related to the viral origin of the disease, to the diffusion of the virus inside nervous system and to the myelin degeneration in the light of the recent literature.", "contents": "[Histological and ultrastructural features of a case of subacute sclerosing panencephalitis (author's transl)]. A case of subacute sclerosing panencephalitis is described from a clinical, histopathological and ultrastructural point of view. The most notable morphologic feature is the presence of a great number of nuclear inclusions inside both neurons and oligodendroglial cells. These inclusions are spread to the whole brain and are decreasing in number from the cerebral cortex towards midbrain. The cerebellum is completely spared. The Authors discuss the problems related to the viral origin of the disease, to the diffusion of the virus inside nervous system and to the myelin degeneration in the light of the recent literature."}
{"id": "PMID:224447", "title": "Effects of serum and cations on the selective release of granular proteins from human netrophils during phagocytosis.", "content": "The extracellular release from human neutrophils of the primary (azurophil) granule constituents, myeloperoxidase (MPO), chymotrypsin-like cationic protein (CCP), collagenase and lysozyme, and the secondary (specific) granule constituents, lactoferrin and lysozyme, was measured during ingestion of staphylococcus protein-A-IgG complexes. In buffer, lactoferrin release was consistently higher than that of the other protein. In serum, lactoferrin release increased concomitantly with ingestion, whereas the rate of lysozyme and especially of MPO release were stimulated to a higher degree than ingestion. Magnesium (0.5--2 mM) was more potent than calcium (0.5--2 mM) in promoting release but these cations worked synergistically. Zinc (0.5--4 mM) was found to be a potent and selective inhibitor of collagenase release. Manganese (0.25--4 mM), which inhibited the ingestion of SpA-IgG complexes, also inhibited release of CCP, collagenase, lysozyme and MPO, but actually stimulated lactoferrin release. The data suggests that lactoferrin and lysozyme may be confined to distinct granule populations or else released in a different fashion from the granules. When the effects on release of primary granule proteins are concerned it is suggested that the dissociation of binding of various agents to an anionic granule matrix may be affected differently by various cations.", "contents": "Effects of serum and cations on the selective release of granular proteins from human netrophils during phagocytosis. The extracellular release from human neutrophils of the primary (azurophil) granule constituents, myeloperoxidase (MPO), chymotrypsin-like cationic protein (CCP), collagenase and lysozyme, and the secondary (specific) granule constituents, lactoferrin and lysozyme, was measured during ingestion of staphylococcus protein-A-IgG complexes. In buffer, lactoferrin release was consistently higher than that of the other protein. In serum, lactoferrin release increased concomitantly with ingestion, whereas the rate of lysozyme and especially of MPO release were stimulated to a higher degree than ingestion. Magnesium (0.5--2 mM) was more potent than calcium (0.5--2 mM) in promoting release but these cations worked synergistically. Zinc (0.5--4 mM) was found to be a potent and selective inhibitor of collagenase release. Manganese (0.25--4 mM), which inhibited the ingestion of SpA-IgG complexes, also inhibited release of CCP, collagenase, lysozyme and MPO, but actually stimulated lactoferrin release. The data suggests that lactoferrin and lysozyme may be confined to distinct granule populations or else released in a different fashion from the granules. When the effects on release of primary granule proteins are concerned it is suggested that the dissociation of binding of various agents to an anionic granule matrix may be affected differently by various cations."}
{"id": "PMID:224448", "title": "Serum and plasma myeloperoxidase, elastase and lactoferrin content in acute myeloid leukaemia.", "content": "Myeloperoxidase (MPO) and elastase, restricted to azurophil granules of neutrophils, as well as lactoferrin, restricted to specific granules of neutrophils, were determined in plasma and serum from patients with acute myeloid leukaemia (AML). Highly sensitive radio immuno assays were developed for detection of these proteins. Serum MPO was increased in 12/35 and decreased in 2/35 patients without correlation to WBC or neutrophil counts; these levels may reflect an abnormal production by leukaemic blasts or ineffective granulopoiesis in the bone marrow. Serum elastase was increased in 6/22 patients. Serum lactoferrin was decreased in 12/25 patients without correlation to neutrophil counts probably reflecting abnormal production. Serum elastase and MPO showed a covariation in chronic myeloid leukaemia but not in AML; the latter finding may indicate that the synthesis of these two proteins is not synchronized in AML-cells. Sequential studies of patients with AML demonstrated fluctuations of serum MPO and lactoferrin during remission most likely because of chemotherapeutic pertubation. Although a limited number of patients has been studied it is suggested that serum lactoferrin may be of help for prediction of relapse in AML.", "contents": "Serum and plasma myeloperoxidase, elastase and lactoferrin content in acute myeloid leukaemia. Myeloperoxidase (MPO) and elastase, restricted to azurophil granules of neutrophils, as well as lactoferrin, restricted to specific granules of neutrophils, were determined in plasma and serum from patients with acute myeloid leukaemia (AML). Highly sensitive radio immuno assays were developed for detection of these proteins. Serum MPO was increased in 12/35 and decreased in 2/35 patients without correlation to WBC or neutrophil counts; these levels may reflect an abnormal production by leukaemic blasts or ineffective granulopoiesis in the bone marrow. Serum elastase was increased in 6/22 patients. Serum lactoferrin was decreased in 12/25 patients without correlation to neutrophil counts probably reflecting abnormal production. Serum elastase and MPO showed a covariation in chronic myeloid leukaemia but not in AML; the latter finding may indicate that the synthesis of these two proteins is not synchronized in AML-cells. Sequential studies of patients with AML demonstrated fluctuations of serum MPO and lactoferrin during remission most likely because of chemotherapeutic pertubation. Although a limited number of patients has been studied it is suggested that serum lactoferrin may be of help for prediction of relapse in AML."}
{"id": "PMID:224449", "title": "High-density lipoprotein as carrier for amyloid-related protein SAA in rabbit serum.", "content": "In this study present evidence that SAA is complexed to high density lipoprotein (HDL) in rabbit serum and is co-isolated with HDL apoproteins. The binding of SAA to HDL seems to be quite strong, judged from affinity chromatography experiments. The studies did not reveal any interaction between SAA and albumin, and there was no evidence that SAA could complex to itself. By isolation of HDL apoproteins, SAA seems to behave like other known apoproteins and may be characterized as an apoprotein that is present in normal serum in very low concentration but increases in concentration under different unphysiological circumstances.", "contents": "High-density lipoprotein as carrier for amyloid-related protein SAA in rabbit serum. In this study present evidence that SAA is complexed to high density lipoprotein (HDL) in rabbit serum and is co-isolated with HDL apoproteins. The binding of SAA to HDL seems to be quite strong, judged from affinity chromatography experiments. The studies did not reveal any interaction between SAA and albumin, and there was no evidence that SAA could complex to itself. By isolation of HDL apoproteins, SAA seems to behave like other known apoproteins and may be characterized as an apoprotein that is present in normal serum in very low concentration but increases in concentration under different unphysiological circumstances."}
{"id": "PMID:224450", "title": "Substrate specificity of the human lymphokine leucocyte migration-inhibitory factor (LIF): radioenzymic assay and inhibition by cGMP.", "content": "The human lymphokine, leucocyte migration-inhibitory factor (LIF), appears to be a serine esterase and protease by virtue of its susceptibility to the irreversible enzyme inhibitor, phenylmethylsulfonyl fluoride (PMSF), and by the ability of arginine esters and amides to protect LIF against PMSF-induced inactivation. In this paper, three methods are described by which putative substrates for LIF may be investigated. Thus, molecules satisfying the substrate specificities of this lymphokine should (1) protect LIF against inactivation by PMSF, (2) reduce LIF activity in vitro on polymorphonuclear leucocytes, and (3) reduce the esterolytic activity of purified LIF-rich supernatants. The first two reactions were tested by means of the leucocyte migration agarose technique; the third reaction was tested by a sensitive enzyme assay using tritiated tosyl arginine methyl ester as substrate. Guanosine 3',5'-cyclic monophosphoric acid, which is capable of protecting LIF against PMSF-induced inhibition, also inhibited the esterolytic activity of the purified LIF preparation. Four synthetic oligopeptide substrates for trypsin, thombin and plasmin were investigated. Only one, the thrombin- and trypsin-specific benzoyl-phenylalanyl-valyl-agarine-p-nitroanilide, possessed high affinity for the LIF molecule and may therefore prove to be a potent substrate for this lymphokine.", "contents": "Substrate specificity of the human lymphokine leucocyte migration-inhibitory factor (LIF): radioenzymic assay and inhibition by cGMP. The human lymphokine, leucocyte migration-inhibitory factor (LIF), appears to be a serine esterase and protease by virtue of its susceptibility to the irreversible enzyme inhibitor, phenylmethylsulfonyl fluoride (PMSF), and by the ability of arginine esters and amides to protect LIF against PMSF-induced inactivation. In this paper, three methods are described by which putative substrates for LIF may be investigated. Thus, molecules satisfying the substrate specificities of this lymphokine should (1) protect LIF against inactivation by PMSF, (2) reduce LIF activity in vitro on polymorphonuclear leucocytes, and (3) reduce the esterolytic activity of purified LIF-rich supernatants. The first two reactions were tested by means of the leucocyte migration agarose technique; the third reaction was tested by a sensitive enzyme assay using tritiated tosyl arginine methyl ester as substrate. Guanosine 3',5'-cyclic monophosphoric acid, which is capable of protecting LIF against PMSF-induced inhibition, also inhibited the esterolytic activity of the purified LIF preparation. Four synthetic oligopeptide substrates for trypsin, thombin and plasmin were investigated. Only one, the thrombin- and trypsin-specific benzoyl-phenylalanyl-valyl-agarine-p-nitroanilide, possessed high affinity for the LIF molecule and may therefore prove to be a potent substrate for this lymphokine."}
{"id": "PMID:224451", "title": "[Histology of cerebellar metastasis of bronchial oat cell carcinoma].", "content": "Anatomo-pathological examination of 28 bronchic oat-cell carcinoma, all with cerebellar metastases and which are very often cerebral. In half of the cases, these localized cerebellar metastases contain palisades. These formations which haven't been described until now within intracranial metastases, can't be considered as artefacts as their frequency approaches 50% of the cases. Neither the primitive tumor nor the extracerebral metastases of the series reveal palisades; sometimes some of them exist in their cerebral metastases. As far as the epidemiology, the clinical evolution, the survival time and the extracerebral localization are concerned, these 28 cases are not different from those described in medical literature. The morphological, hormonal and biochemical knowledge we possess about this type of cancer tends to prove its neuroectodermic origin as well as its close relation with both the APUD- and the \"endocrinien diffus\" systems. The described palisading elements represent another very specific morphological point which tends to support this theory: they appear principally in the tumors of the central and peripheral nervous system. Although the author is not able to explain the reason of palisades' genesis in cerebellar metastases, he insists on the fact that it iw very important - as far as every days' biopsy's study is concerned - to proceed to a differential histological diagnosis in regards to certain primitive tumors of the nervous system (among these the medulloblastoma) and a cerebellar metastasis of this type of bronchic carcinoma.", "contents": "[Histology of cerebellar metastasis of bronchial oat cell carcinoma]. Anatomo-pathological examination of 28 bronchic oat-cell carcinoma, all with cerebellar metastases and which are very often cerebral. In half of the cases, these localized cerebellar metastases contain palisades. These formations which haven't been described until now within intracranial metastases, can't be considered as artefacts as their frequency approaches 50% of the cases. Neither the primitive tumor nor the extracerebral metastases of the series reveal palisades; sometimes some of them exist in their cerebral metastases. As far as the epidemiology, the clinical evolution, the survival time and the extracerebral localization are concerned, these 28 cases are not different from those described in medical literature. The morphological, hormonal and biochemical knowledge we possess about this type of cancer tends to prove its neuroectodermic origin as well as its close relation with both the APUD- and the \"endocrinien diffus\" systems. The described palisading elements represent another very specific morphological point which tends to support this theory: they appear principally in the tumors of the central and peripheral nervous system. Although the author is not able to explain the reason of palisades' genesis in cerebellar metastases, he insists on the fact that it iw very important - as far as every days' biopsy's study is concerned - to proceed to a differential histological diagnosis in regards to certain primitive tumors of the nervous system (among these the medulloblastoma) and a cerebellar metastasis of this type of bronchic carcinoma."}
{"id": "PMID:224452", "title": "Mediastinal tumours and cysts. A review of 91 cases.", "content": "The experience with 91 primary tumours of the mediastinum during a period of 20 years is presented. A total of 24 separate cell types were identified. The most frequent lesions were thyroid tumours, neurogenic tumours, cysts and tumours of lymphatic origin. About 50% of the tumours were discovered by chance in asymptomatic patients undergoing routine chest examination. Twenty per cent of the patients with malignant lesions were free of symptoms. The pre-operative diagnosis was uncertain in most instances, and early surgical exploration is therefore recommended. Seventy-four patients underwent surgery and the operative mortality rate was 2.7%. The long-term survival was closely related to the histological nature of the neoplasm.", "contents": "Mediastinal tumours and cysts. A review of 91 cases. The experience with 91 primary tumours of the mediastinum during a period of 20 years is presented. A total of 24 separate cell types were identified. The most frequent lesions were thyroid tumours, neurogenic tumours, cysts and tumours of lymphatic origin. About 50% of the tumours were discovered by chance in asymptomatic patients undergoing routine chest examination. Twenty per cent of the patients with malignant lesions were free of symptoms. The pre-operative diagnosis was uncertain in most instances, and early surgical exploration is therefore recommended. Seventy-four patients underwent surgery and the operative mortality rate was 2.7%. The long-term survival was closely related to the histological nature of the neoplasm."}
{"id": "PMID:224454", "title": "Trigeminal ganglion infection by thymidine kinase-negative mutants of herpes simplex virus.", "content": "The incidence of trigeminal ganglion infection after corneal inoculation of guinea pigs with thymidine kinase-negative mutants of herpes simplex virus was markedly reduced compared to infection after inoculation of thymidine kinase-positive virus. Thymidine kinase-negative herpes simplex virus replicated well in ocular tissues in which dividing or potentially dividing cells were present, but not in trigeminal ganglion infection of nondividing neurons. Thymidine kinase-positive virus, however, replicated well in ocular tissues as well as in trigeminal ganglion. These results suggest that thymidine kinase expression of herpes simplex virus may be important in infections of sensory ganglia.", "contents": "Trigeminal ganglion infection by thymidine kinase-negative mutants of herpes simplex virus. The incidence of trigeminal ganglion infection after corneal inoculation of guinea pigs with thymidine kinase-negative mutants of herpes simplex virus was markedly reduced compared to infection after inoculation of thymidine kinase-positive virus. Thymidine kinase-negative herpes simplex virus replicated well in ocular tissues in which dividing or potentially dividing cells were present, but not in trigeminal ganglion infection of nondividing neurons. Thymidine kinase-positive virus, however, replicated well in ocular tissues as well as in trigeminal ganglion. These results suggest that thymidine kinase expression of herpes simplex virus may be important in infections of sensory ganglia."}
{"id": "PMID:224455", "title": "Digitalis genin activity: side-group carbonyl oxygen position is a major determinant.", "content": "The Na+,k+-adenosine triphosphatase-inhibiting activity of digitalis genins and their analogs is a function of side-group carbonyl (C = O) oxygen position. For each 2.2 angstroms that this oxygen is displaced from its position in digitoxigenin, activity drops by one order of magnitude. This quantitative relation resolves previously proposed models which have attempted to describe the molecular basis of genin activity. A multidisciplinary (crystallographic, conformational energy, synthetic, biological) approach to structure-activity relations is described.", "contents": "Digitalis genin activity: side-group carbonyl oxygen position is a major determinant. The Na+,k+-adenosine triphosphatase-inhibiting activity of digitalis genins and their analogs is a function of side-group carbonyl (C = O) oxygen position. For each 2.2 angstroms that this oxygen is displaced from its position in digitoxigenin, activity drops by one order of magnitude. This quantitative relation resolves previously proposed models which have attempted to describe the molecular basis of genin activity. A multidisciplinary (crystallographic, conformational energy, synthetic, biological) approach to structure-activity relations is described."}
{"id": "PMID:224456", "title": "Chronic zinc deficiency alters neuronal function of hippocampal mossy fibers.", "content": "Low-frequency stimulation of hippocampal mossy fiber axons in zinc-deficient adult rats produced synaptic responses that declined in amplitude with successive stimuli. This response decrement is abnormal and suggests that the heavy deposits of zinc in mossy fiber boutons are important for synaptic transmission.", "contents": "Chronic zinc deficiency alters neuronal function of hippocampal mossy fibers. Low-frequency stimulation of hippocampal mossy fiber axons in zinc-deficient adult rats produced synaptic responses that declined in amplitude with successive stimuli. This response decrement is abnormal and suggests that the heavy deposits of zinc in mossy fiber boutons are important for synaptic transmission."}
{"id": "PMID:224457", "title": "Specific nonopiate receptors for beta-endorphin.", "content": "Iodinated beta H-[2-D-alanine]endorphin exhibits specific binding to cultured human lymphocytes. The binding is inhibited by low concentrations of beta-endorphin and its D-alanine derivative, but is not affected by opiate agonists and antagonists, or by enkephalin analogs, beta-lipotropin, adrenocorticotrophic hormone, or alpha-melanocyte-stimulating hormone; this suggests the existence of a specific, non-opiate binding site (receptor) for beta-endorphin. The carboxy-terminal region of beta-endorphin is essential for this binding activity, since alpha-endorphin is not active. beta-Endorphin may be a circulating hormone with peripheral physiological effects that are not primarily mediated through interactions with opiate or enkephalin receptors.", "contents": "Specific nonopiate receptors for beta-endorphin. Iodinated beta H-[2-D-alanine]endorphin exhibits specific binding to cultured human lymphocytes. The binding is inhibited by low concentrations of beta-endorphin and its D-alanine derivative, but is not affected by opiate agonists and antagonists, or by enkephalin analogs, beta-lipotropin, adrenocorticotrophic hormone, or alpha-melanocyte-stimulating hormone; this suggests the existence of a specific, non-opiate binding site (receptor) for beta-endorphin. The carboxy-terminal region of beta-endorphin is essential for this binding activity, since alpha-endorphin is not active. beta-Endorphin may be a circulating hormone with peripheral physiological effects that are not primarily mediated through interactions with opiate or enkephalin receptors."}
{"id": "PMID:224458", "title": "Molecular cloning of polyoma virus DNA in Escherichia coli: oncogenicity testing in hamsters.", "content": "Inoculation of suckling hamsters with 2 x 10(8) live cells of Escherichia coli K12 strain chi1776, carrying the complete genome of polyoma virus in a recombinant plasmid, failed to induce tumors in any of 32 recipients. Also, lambda phage DNA and particles with a monomeric insert of polyoma DNA did not induce tumors. Purified recombinant plasmid DNA, as well as phage particles and DNA containing a head-to-tail dimer of polyoma DNA, showed a low degree of oncogenicity, comparable to that of polyoma DNA prepared from mouse cells. These findings support the previous conclusions, based on infectivity assays in mice, that propagation of polyoma virus DNA as a component of recombinant DNA molecules in E. coli K12 reduces its biologic activity many orders of magnitude relative to the virus itself.", "contents": "Molecular cloning of polyoma virus DNA in Escherichia coli: oncogenicity testing in hamsters. Inoculation of suckling hamsters with 2 x 10(8) live cells of Escherichia coli K12 strain chi1776, carrying the complete genome of polyoma virus in a recombinant plasmid, failed to induce tumors in any of 32 recipients. Also, lambda phage DNA and particles with a monomeric insert of polyoma DNA did not induce tumors. Purified recombinant plasmid DNA, as well as phage particles and DNA containing a head-to-tail dimer of polyoma DNA, showed a low degree of oncogenicity, comparable to that of polyoma DNA prepared from mouse cells. These findings support the previous conclusions, based on infectivity assays in mice, that propagation of polyoma virus DNA as a component of recombinant DNA molecules in E. coli K12 reduces its biologic activity many orders of magnitude relative to the virus itself."}
{"id": "PMID:224459", "title": "[3H]GABA binding in brains from Huntington's chorea patients: altered regulation by phospholipids?", "content": "Binding sites for tritum-labeled gamma-aminobutyric acid (GABA) in cerebellar cortex of Huntington's chorea patients have an increased affinity but unaltered maximum capacity as compared to binding sites in tissue from control patients. A similar binding pattern is produced in control membranes by treatment with Triton X-100, phospholipase C, or glycerophosphoethanolamine. Thus, it is likely that phospholipids or their metabolites regulate the accessibility of the GABA binding site and that this regulation is abnormal in Huntington's chorea.", "contents": "[3H]GABA binding in brains from Huntington's chorea patients: altered regulation by phospholipids? Binding sites for tritum-labeled gamma-aminobutyric acid (GABA) in cerebellar cortex of Huntington's chorea patients have an increased affinity but unaltered maximum capacity as compared to binding sites in tissue from control patients. A similar binding pattern is produced in control membranes by treatment with Triton X-100, phospholipase C, or glycerophosphoethanolamine. Thus, it is likely that phospholipids or their metabolites regulate the accessibility of the GABA binding site and that this regulation is abnormal in Huntington's chorea."}
{"id": "PMID:224460", "title": "Starvation-induced decreased sensitivity of resting metabolic rate to triiodothyronine.", "content": "The decrease in resting oxygen consumption induced by starvation was found to occur not only in euthyroid rats but also in hypothyroid and even in hypothyroid animals treated with triiodothyronine. Furthermore, the effectiveness of triiodothyronine was decreased when given to hypothyroid animals.", "contents": "Starvation-induced decreased sensitivity of resting metabolic rate to triiodothyronine. The decrease in resting oxygen consumption induced by starvation was found to occur not only in euthyroid rats but also in hypothyroid and even in hypothyroid animals treated with triiodothyronine. Furthermore, the effectiveness of triiodothyronine was decreased when given to hypothyroid animals."}
{"id": "PMID:224461", "title": "Thyrotropin-releasing hormone selectively depresses glutamate excitation of cerebral cortical neurons.", "content": "The microiontophoretic application of thyrotropin-releasing hormone causes a selective reduction in neuronal excitation evoked by L-glutamate but not by acetylcholine in rat cerebral cortex. Thyrotropin-releasing hormone has no influence on the activity of acetylcholinesterase or on choline uptake and release from cerebral synaptosomes. This evidence for a selective interaction between a centrally acting peptide and an excitatory amino acid neurotransmitter may indicate a specific locus of thyrotropin-releasing hormone action at glutamate-activated receptor sites.", "contents": "Thyrotropin-releasing hormone selectively depresses glutamate excitation of cerebral cortical neurons. The microiontophoretic application of thyrotropin-releasing hormone causes a selective reduction in neuronal excitation evoked by L-glutamate but not by acetylcholine in rat cerebral cortex. Thyrotropin-releasing hormone has no influence on the activity of acetylcholinesterase or on choline uptake and release from cerebral synaptosomes. This evidence for a selective interaction between a centrally acting peptide and an excitatory amino acid neurotransmitter may indicate a specific locus of thyrotropin-releasing hormone action at glutamate-activated receptor sites."}
{"id": "PMID:224462", "title": "Morphine-naloxone interactions: a role for nonspecific morphine excitatory effects in withdrawal.", "content": "The opiate antagonist naloxone precipitates withdrawal when given either 15 minutes after or 1 minute before a single injection of morphine in drug-na\u00efve mice. We propose that withdrawal signs arise from a synergistic mixture of excitatory influences that are direct (agonistic action on nonspecific opiate receptors) and indirect (sensory and affective disorders, stress, hormonal and neurotransmitter dysfunction, and so forth). The predominant effects during precipitated withdrawal are assumed to be direct, whereas during abstinence in tolerant animals they are indirect.", "contents": "Morphine-naloxone interactions: a role for nonspecific morphine excitatory effects in withdrawal. The opiate antagonist naloxone precipitates withdrawal when given either 15 minutes after or 1 minute before a single injection of morphine in drug-na\u00efve mice. We propose that withdrawal signs arise from a synergistic mixture of excitatory influences that are direct (agonistic action on nonspecific opiate receptors) and indirect (sensory and affective disorders, stress, hormonal and neurotransmitter dysfunction, and so forth). The predominant effects during precipitated withdrawal are assumed to be direct, whereas during abstinence in tolerant animals they are indirect."}
{"id": "PMID:224463", "title": "Cyclic AMP receptor triggers nuclear protein phosphorylation in a hormone-dependent mammary tumor cell-free system.", "content": "Adenosine 3',5'-monophosphate (cyclic AMP) receptor protein of 56,000 daltons increases markedly in mammary tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) after incubation of tumor slices with cyclic AMP, benzamide, and arginine. Incubation of cytosol from these tumor slices with nuclei from unincubated tumors results in nuclear uptake of the 56,000-dalton cyclic AMP receptor and in phosphorylation of the 76,000-dalton nuclear protein. Binding of the 56,000-dalton receptor and phosphorylation of the 76,000-dalton protein also occur in DMBA tumor nuclei when protein kinase type II of bovine heart is used. The results suggest that cyclic AMP receptor is involved in the nuclear events of a hormone-dependent mammary tumor.", "contents": "Cyclic AMP receptor triggers nuclear protein phosphorylation in a hormone-dependent mammary tumor cell-free system. Adenosine 3',5'-monophosphate (cyclic AMP) receptor protein of 56,000 daltons increases markedly in mammary tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) after incubation of tumor slices with cyclic AMP, benzamide, and arginine. Incubation of cytosol from these tumor slices with nuclei from unincubated tumors results in nuclear uptake of the 56,000-dalton cyclic AMP receptor and in phosphorylation of the 76,000-dalton nuclear protein. Binding of the 56,000-dalton receptor and phosphorylation of the 76,000-dalton protein also occur in DMBA tumor nuclei when protein kinase type II of bovine heart is used. The results suggest that cyclic AMP receptor is involved in the nuclear events of a hormone-dependent mammary tumor."}
{"id": "PMID:224464", "title": "Substance P: evidence for diverse roles in neuronal function from cultured mouse spinal neurons.", "content": "Mouse spinal neurons grown in tissue culture were used to examine the membrane mechanisms of action of the peptide substance P. Two functionally distinct actions were observed, one being a rapidly desensitizing excitation, and the other being a dose-dependent, reversible depression of excitatory responses to the putative amino acid neurotransmitter glutamate. These effects on excitability suggest that substance P may play more than one role in intercellular communication in the nervous system.", "contents": "Substance P: evidence for diverse roles in neuronal function from cultured mouse spinal neurons. Mouse spinal neurons grown in tissue culture were used to examine the membrane mechanisms of action of the peptide substance P. Two functionally distinct actions were observed, one being a rapidly desensitizing excitation, and the other being a dose-dependent, reversible depression of excitatory responses to the putative amino acid neurotransmitter glutamate. These effects on excitability suggest that substance P may play more than one role in intercellular communication in the nervous system."}
{"id": "PMID:224467", "title": "[Crohn's disease of the colon. History].", "content": "During the 18th, 19th, and at the beginning of the 20th century, various observations of inflammatory lesions of the colon and small intestine were published, which were different of tuberculosis to which was at that time attributed every chronical small intestinal inflammatory disease. It was only in 1932, that in a very important paper, Crohn, Ginsburg and Oppenheimer defined the terminal ileitis, afterwards called regional enteritis, and finally more simply Crohn's disease. Twenty years later, in 1952, Crohn's disease of the colon, confused until that date with colonic tuberculosis and with ulcerative colitis, was also identified as a separate entity. Since that time, the number of reported cases has tremendously increased through its is impossible to state whether the incidence of the disease has really increased or whether the diagnosis is done earlier and more precisely. Even today, the exacts limits of the disease are difficult to precise, since the causal agent of the disease is unknown, and that no biological test is completely secure. The present work reports 60 observations of chronic colitis, associated or not with small intestinal inflammation.", "contents": "[Crohn's disease of the colon. History]. During the 18th, 19th, and at the beginning of the 20th century, various observations of inflammatory lesions of the colon and small intestine were published, which were different of tuberculosis to which was at that time attributed every chronical small intestinal inflammatory disease. It was only in 1932, that in a very important paper, Crohn, Ginsburg and Oppenheimer defined the terminal ileitis, afterwards called regional enteritis, and finally more simply Crohn's disease. Twenty years later, in 1952, Crohn's disease of the colon, confused until that date with colonic tuberculosis and with ulcerative colitis, was also identified as a separate entity. Since that time, the number of reported cases has tremendously increased through its is impossible to state whether the incidence of the disease has really increased or whether the diagnosis is done earlier and more precisely. Even today, the exacts limits of the disease are difficult to precise, since the causal agent of the disease is unknown, and that no biological test is completely secure. The present work reports 60 observations of chronic colitis, associated or not with small intestinal inflammation."}
{"id": "PMID:224468", "title": "[Pathology of the Crohn's disease of colon (author's transl)].", "content": "The examination of 43 postoperative specimens and of 51 biopsic specimens of the rectum concerning colic Crohn's disease (MCC) confirm the known macroscopic and histologic characteristics of this disease. The epithelioid and gigant cell granuloma is rarely observed in the biopsic specimens of the rectum, and it is not always observed even on post operative specimens (only in 40% of the cases). The other characteristics and in particular the small \"serous lymphohistiocytic perivascular infiltrates\" should be taken into account when making the diagnosis. At the present time, there are still a certain number of forms of ulcerative colitis which cannot be classified, and the characteristics of which are both those of the MCC and of the RCUH.", "contents": "[Pathology of the Crohn's disease of colon (author's transl)]. The examination of 43 postoperative specimens and of 51 biopsic specimens of the rectum concerning colic Crohn's disease (MCC) confirm the known macroscopic and histologic characteristics of this disease. The epithelioid and gigant cell granuloma is rarely observed in the biopsic specimens of the rectum, and it is not always observed even on post operative specimens (only in 40% of the cases). The other characteristics and in particular the small \"serous lymphohistiocytic perivascular infiltrates\" should be taken into account when making the diagnosis. At the present time, there are still a certain number of forms of ulcerative colitis which cannot be classified, and the characteristics of which are both those of the MCC and of the RCUH."}
{"id": "PMID:224469", "title": "[Findings by baryum enema in granulomatous colitis and ileocolitis. A review based upon 60 cases (author's transl)].", "content": "Radiological aspects of colonic involvement in 60 patients whose disease has been followed up during several years are described. The typical radiological findings have been observed with their usual frequency. This study also confirmed the persistancy of the radiological findings in the chronic stage and the frequency of recurence in the two first years after surgery. Extension of disease has not been uncommon in the series, even without surgery. This progression was different, according to the initial location of disease: in the case of initial ileal lesion, extension occurred towards the adjacent caecum and right colon in sequence; in the case of initial colitis or ileocolitis lesion, extension occurred at a distance in other colonic segments.", "contents": "[Findings by baryum enema in granulomatous colitis and ileocolitis. A review based upon 60 cases (author's transl)]. Radiological aspects of colonic involvement in 60 patients whose disease has been followed up during several years are described. The typical radiological findings have been observed with their usual frequency. This study also confirmed the persistancy of the radiological findings in the chronic stage and the frequency of recurence in the two first years after surgery. Extension of disease has not been uncommon in the series, even without surgery. This progression was different, according to the initial location of disease: in the case of initial ileal lesion, extension occurred towards the adjacent caecum and right colon in sequence; in the case of initial colitis or ileocolitis lesion, extension occurred at a distance in other colonic segments."}
{"id": "PMID:224470", "title": "[Extra intestinal manifestations of Crohn's disease (author's transl)].", "content": "The extra intestinal manifestations of Crohn's disease (CD) are not devoid of interest. They can, by themselves, aggravate the CD. Some of them have to be searched systematically (urinary complications, spondylarthritis and sacro-iliac arthritis). Amongst our 60 cases of Crohn's disease of the colon or of the ileon and colon, articular manifestations were the most frequent: arthralgias 25 cases (42%), true arthritis 17 cases (28%), spondylarthritis 5 cases, aacro-ileitis 9 cas (13%), finger hippocratism 11 cases (18%). In second cause, the cutaneous manifestations: 29 cases (48%) among which 6 cases (10%) of erytheme nodosa and 9 cases of allergic troubles (15%). Then came ocular troubles (5 cases), jaundice (5 cases). We observed 4 renal lithiasis and an hepatic sarco\u00efd granuloma revealed by the liver biopsy. Some complications were the local consequence of a local disease (hydronephrosis). Others represented the distant repercussion of a severe chronical intestinal disease. Some were true extra-intestinal localisations of the disease (perineal ulcerations and para-stomal ulcerations). Finally some complications, though non specific of Crohn's disease, evolued in parallel to it (some articular, ocular; dermatologic complications). In some cases they were anterior by several months or years to the intestinal symptoms of Crohn's disease, which suggests the existence of common etiological factors, especially genetical.", "contents": "[Extra intestinal manifestations of Crohn's disease (author's transl)]. The extra intestinal manifestations of Crohn's disease (CD) are not devoid of interest. They can, by themselves, aggravate the CD. Some of them have to be searched systematically (urinary complications, spondylarthritis and sacro-iliac arthritis). Amongst our 60 cases of Crohn's disease of the colon or of the ileon and colon, articular manifestations were the most frequent: arthralgias 25 cases (42%), true arthritis 17 cases (28%), spondylarthritis 5 cases, aacro-ileitis 9 cas (13%), finger hippocratism 11 cases (18%). In second cause, the cutaneous manifestations: 29 cases (48%) among which 6 cases (10%) of erytheme nodosa and 9 cases of allergic troubles (15%). Then came ocular troubles (5 cases), jaundice (5 cases). We observed 4 renal lithiasis and an hepatic sarco\u00efd granuloma revealed by the liver biopsy. Some complications were the local consequence of a local disease (hydronephrosis). Others represented the distant repercussion of a severe chronical intestinal disease. Some were true extra-intestinal localisations of the disease (perineal ulcerations and para-stomal ulcerations). Finally some complications, though non specific of Crohn's disease, evolued in parallel to it (some articular, ocular; dermatologic complications). In some cases they were anterior by several months or years to the intestinal symptoms of Crohn's disease, which suggests the existence of common etiological factors, especially genetical."}
{"id": "PMID:224471", "title": "[Haematologic disorders in Crohn's disease (author's transl)].", "content": "Anemia is the most commonly haematologic disorder observed in Crohn's disease. Secondary megaloblastic anemia related to a nutritional deficiency of vitamin B 12 and/or folic acid is a rare condition as well as auto-immune haemolytic anemia. Iron lack microcytic hypochromic anemia is far more frequent. It is probably due to several causes as microscopic or macroscopic haemorrhages, inflammatory syndrome, disturbance of iron absorption. Hyperleucocytis, hypereosinophilia, hypoprothrombinemia related to the inflammatory syndrome and/or lesions of the bowels are frequently observed in such patients. Anyhow, heamatologic disorders seem markedly correlated with the activity of the disease and should be useful in the follow up patients with Crohn's disease.", "contents": "[Haematologic disorders in Crohn's disease (author's transl)]. Anemia is the most commonly haematologic disorder observed in Crohn's disease. Secondary megaloblastic anemia related to a nutritional deficiency of vitamin B 12 and/or folic acid is a rare condition as well as auto-immune haemolytic anemia. Iron lack microcytic hypochromic anemia is far more frequent. It is probably due to several causes as microscopic or macroscopic haemorrhages, inflammatory syndrome, disturbance of iron absorption. Hyperleucocytis, hypereosinophilia, hypoprothrombinemia related to the inflammatory syndrome and/or lesions of the bowels are frequently observed in such patients. Anyhow, heamatologic disorders seem markedly correlated with the activity of the disease and should be useful in the follow up patients with Crohn's disease."}
{"id": "PMID:224472", "title": "[Psychiatric aspects of Crohn's disease (author's transl)].", "content": "We have examined 13 patients suffering from Crohn's disease, almost all of them during an active spell. Three patients had a well-structured personality, four patients an obsessional one, one patient a narcissistic personality, and five patients a passive-dependant personality structure. Four patients seemed depressed and anxious. The texts dealing with the psychological aspects of Crohn's disease acknowledge the influence of a stress as a precipitating factor. Patients' passivity and dependence is an idea emphasized by several authors, and the frequency of obsessive personality traits is pointed out in different studies. In short, no author allows us to conclude formally in favour of a psychosomatic origin of Crohn's disease, which confirms our impression after examination of the patients we have talked with or seen regularly.", "contents": "[Psychiatric aspects of Crohn's disease (author's transl)]. We have examined 13 patients suffering from Crohn's disease, almost all of them during an active spell. Three patients had a well-structured personality, four patients an obsessional one, one patient a narcissistic personality, and five patients a passive-dependant personality structure. Four patients seemed depressed and anxious. The texts dealing with the psychological aspects of Crohn's disease acknowledge the influence of a stress as a precipitating factor. Patients' passivity and dependence is an idea emphasized by several authors, and the frequency of obsessive personality traits is pointed out in different studies. In short, no author allows us to conclude formally in favour of a psychosomatic origin of Crohn's disease, which confirms our impression after examination of the patients we have talked with or seen regularly."}
{"id": "PMID:224473", "title": "[Medical mangement of Crohn's disease (author's transl)].", "content": "Medical management of Crohn's disease is above all symptomatic. According to the severeness of the case, treatment varies and may be simple (regimen, antidiarrheic agents and sulfamid drugs) or more sophisticated (continous parenteral alimentation). Sulfamids and antibiotics have a definite although temporary action. Pathogenic medication includes: 1) steroid therapy who is active, but its effects are not long stand; 2) immunosuppressors who allow for the reduction of steroid therapy dosages; 3) immunostimulants as proposed by Geffroy. Among those presently studied are Calmette-Gu\u00e9rin vaccine, either given orally or by scarification, and two anti-parasitic drugs, metronidazole and levamisole. Short term results are good but they worsen with time. The main problem is to know when to discuss surgery. As need be, resection although mutilating, should be timely indicated.", "contents": "[Medical mangement of Crohn's disease (author's transl)]. Medical management of Crohn's disease is above all symptomatic. According to the severeness of the case, treatment varies and may be simple (regimen, antidiarrheic agents and sulfamid drugs) or more sophisticated (continous parenteral alimentation). Sulfamids and antibiotics have a definite although temporary action. Pathogenic medication includes: 1) steroid therapy who is active, but its effects are not long stand; 2) immunosuppressors who allow for the reduction of steroid therapy dosages; 3) immunostimulants as proposed by Geffroy. Among those presently studied are Calmette-Gu\u00e9rin vaccine, either given orally or by scarification, and two anti-parasitic drugs, metronidazole and levamisole. Short term results are good but they worsen with time. The main problem is to know when to discuss surgery. As need be, resection although mutilating, should be timely indicated."}
{"id": "PMID:224474", "title": "[Surgical treatment of Crohn disease of the colon. (38 cases) (author's transl)].", "content": "From 1959 to december 1972 thirty-eight patients out of sixty having Crohn disease of the colon alone or with ileal and/or rectal involvement were operated upon. We had four post-operative deaths and one a long time after the intervention, but in relation with the initial Crohn disease. These thirty-eight patients had sixty-seven operations. Only fifty-five per cent of the operated on patients did not have any complications. Twenty-three patients had recurrence of the disease, seven of them were re-operated for this first recurrence, two of them for a second recurrence and one of these two last patients had a third recurrence. That makes twenty-seven recurrences out of forty-three resections. Among these twenty-seven recurrences, in at least seventeen cases, resection was not large enough or was not radical. Three quarters of the recurrences appear during the first year. The more exposed interventions to recurrences are left hemi-colectomies (two out of two) and total colectomies with ileo-rectal anastomosis (six out of eight). The ones that give less recurrences are total colo-protectomies or subtotal colectomies (one recurrence out of nine). Indications for the different types of interventions are analysed. Management of the rectum in Crohn disease of the colon is difficult. Procedures applied for toxic megacolon are equally very critical.", "contents": "[Surgical treatment of Crohn disease of the colon. (38 cases) (author's transl)]. From 1959 to december 1972 thirty-eight patients out of sixty having Crohn disease of the colon alone or with ileal and/or rectal involvement were operated upon. We had four post-operative deaths and one a long time after the intervention, but in relation with the initial Crohn disease. These thirty-eight patients had sixty-seven operations. Only fifty-five per cent of the operated on patients did not have any complications. Twenty-three patients had recurrence of the disease, seven of them were re-operated for this first recurrence, two of them for a second recurrence and one of these two last patients had a third recurrence. That makes twenty-seven recurrences out of forty-three resections. Among these twenty-seven recurrences, in at least seventeen cases, resection was not large enough or was not radical. Three quarters of the recurrences appear during the first year. The more exposed interventions to recurrences are left hemi-colectomies (two out of two) and total colectomies with ileo-rectal anastomosis (six out of eight). The ones that give less recurrences are total colo-protectomies or subtotal colectomies (one recurrence out of nine). Indications for the different types of interventions are analysed. Management of the rectum in Crohn disease of the colon is difficult. Procedures applied for toxic megacolon are equally very critical."}
{"id": "PMID:224476", "title": "[Seasonal variations of cellular composition of human semen (author's transl)].", "content": "Sperm samples taken fortnightly from 14 young europeans over a period of 8 months show evidence of a seasonal variation in the concentration of spermatozoa and in the frequency of abnormal sperm (teratospermy). Both factors are highest in winter and lowest in springtime. A study of 3,000 spermograms established during consultations for sterility over the last 2 years did not clearly reveal the same trends, however, a statistical analysis of the results leads to the conclusion that several hundred examinations per month would be needed to show a significant seasonal variation in such a heterogeneous sample.", "contents": "[Seasonal variations of cellular composition of human semen (author's transl)]. Sperm samples taken fortnightly from 14 young europeans over a period of 8 months show evidence of a seasonal variation in the concentration of spermatozoa and in the frequency of abnormal sperm (teratospermy). Both factors are highest in winter and lowest in springtime. A study of 3,000 spermograms established during consultations for sterility over the last 2 years did not clearly reveal the same trends, however, a statistical analysis of the results leads to the conclusion that several hundred examinations per month would be needed to show a significant seasonal variation in such a heterogeneous sample."}
{"id": "PMID:224475", "title": "[About five cases of congenital german measle (author's transl)].", "content": "The authors are reporting five cases of congenital german measles confirmed by serological and virological tests. They recall the circumstances in which the serological diagnosis of maternal german measles was arrived at during pregnancy: misinterpretation of the results had in four cases given the doctor a mistaken sense of security. Lastly, they are stressing the interest of prevention by systematic vaccination of girls aged 11 to 13 and women known to be seronegative.", "contents": "[About five cases of congenital german measle (author's transl)]. The authors are reporting five cases of congenital german measles confirmed by serological and virological tests. They recall the circumstances in which the serological diagnosis of maternal german measles was arrived at during pregnancy: misinterpretation of the results had in four cases given the doctor a mistaken sense of security. Lastly, they are stressing the interest of prevention by systematic vaccination of girls aged 11 to 13 and women known to be seronegative."}
{"id": "PMID:224477", "title": "[Leptospirosis in children: a not infrequent disease (author's transl)].", "content": "A total of 14 cases of leptospirosis in children aged from 5 to 15 years, hospitalized in the Paris region, are reported. The polymorphe character of the disease is pointed out. The necessity for respecting a rigorous chronological order when requesting complementary examinations, which could confirm the diagnosis, is stressed. Domestic animals, team-mates, and while swimming at week-ends or during holidays, are potential sources or means of infection in the young. This justifies searching for leptospirosis in cases of unexplained fever, a pseudo-influenza syndrome, a meningitis which is mainly of the lymphocytic type, or more rarely, in cases of jaundice. Leptospirosis should be a disease well-known by the pediatrician.", "contents": "[Leptospirosis in children: a not infrequent disease (author's transl)]. A total of 14 cases of leptospirosis in children aged from 5 to 15 years, hospitalized in the Paris region, are reported. The polymorphe character of the disease is pointed out. The necessity for respecting a rigorous chronological order when requesting complementary examinations, which could confirm the diagnosis, is stressed. Domestic animals, team-mates, and while swimming at week-ends or during holidays, are potential sources or means of infection in the young. This justifies searching for leptospirosis in cases of unexplained fever, a pseudo-influenza syndrome, a meningitis which is mainly of the lymphocytic type, or more rarely, in cases of jaundice. Leptospirosis should be a disease well-known by the pediatrician."}
{"id": "PMID:224478", "title": "[Treatment of 100 acute myeloid leukemias (author's transl)].", "content": "Between november 1974 and august 1976, 100 acute myelo\u00efd leukemias were treated by the same protocol L. 275. Induction treatment was daunorubicine, vincristine, cytosine arabinoside, in one intensive course for patients under 65 and cyclophosphamide (CPM), VCR and CAR in a less intensive and repetitive courses for patients over 65. In remission, there were three phases: consolidation, prevention of central nervous system leukemia, maintenance. All patients in remission received an androgenotherapy and two groups were randomised: chemotherapy and chemotherapy plus BCG. 68 patients were in complet remission (CR) 61 out of 80 patients under 65 and 7 out of 20 over 65. Median duration of first remission was 12 months. Median duration of survival was 13 months for all patients, 15 months for patients under 65, 3 months for patients over 65, and 22 months for 68 patients in CR. Survival of patients receiving BCG was slightly better than patients without BCG.", "contents": "[Treatment of 100 acute myeloid leukemias (author's transl)]. Between november 1974 and august 1976, 100 acute myelo\u00efd leukemias were treated by the same protocol L. 275. Induction treatment was daunorubicine, vincristine, cytosine arabinoside, in one intensive course for patients under 65 and cyclophosphamide (CPM), VCR and CAR in a less intensive and repetitive courses for patients over 65. In remission, there were three phases: consolidation, prevention of central nervous system leukemia, maintenance. All patients in remission received an androgenotherapy and two groups were randomised: chemotherapy and chemotherapy plus BCG. 68 patients were in complet remission (CR) 61 out of 80 patients under 65 and 7 out of 20 over 65. Median duration of first remission was 12 months. Median duration of survival was 13 months for all patients, 15 months for patients under 65, 3 months for patients over 65, and 22 months for 68 patients in CR. Survival of patients receiving BCG was slightly better than patients without BCG."}
{"id": "PMID:224479", "title": "[Paroxysmal paralytic myoglobinuria. Restatement according to a personal observation (author's transl)].", "content": "The authors relate the case of a 24 year old man with deadly evolution in keeping with a paroxysmal paralytic myoglobinuria. Clinical, biological and histological studies of this disease are successively recorded. The pathogenesis is obscure. Symptomatic medical treatment must be supervise in an intensive department.", "contents": "[Paroxysmal paralytic myoglobinuria. Restatement according to a personal observation (author's transl)]. The authors relate the case of a 24 year old man with deadly evolution in keeping with a paroxysmal paralytic myoglobinuria. Clinical, biological and histological studies of this disease are successively recorded. The pathogenesis is obscure. Symptomatic medical treatment must be supervise in an intensive department."}
{"id": "PMID:224480", "title": "[Therapy of bacterial infections occuring during aplastic phasis of acute leukemias (author's transl)].", "content": "On a three years' period, 122 patients with AL (45 children, 76 adults) received 158 treatments of induction, involving a severe medullary aplasia. In 48 cases (30.4%) none infectious complication was recorded. In the other 110 observations, infections syndrome (septicemia due to gram-negative rods above all) was treated by an early and intensive combination antibiotherapy (three successive protocols are employed, after failure of the precedent), in association with a careful medical reanimation and trasfusions of granulocytes in 16 cases. Regression was obtained in 94 cases (59,5%) but infection was lethal in 16 patients (10.1%). More than cytological variety of AL, principal pronostic element is age (15 deaths among 88 infections episodes in adults, one among 22 in children). Granulocytes rate at the time of aplasia (lower than 500 /mm3) also represents a factor of gravity. Among 94 infections episodes, antibiotherapy was successful alone in 81 cases (86.2%), illustrating the fundamental place of this treatment.", "contents": "[Therapy of bacterial infections occuring during aplastic phasis of acute leukemias (author's transl)]. On a three years' period, 122 patients with AL (45 children, 76 adults) received 158 treatments of induction, involving a severe medullary aplasia. In 48 cases (30.4%) none infectious complication was recorded. In the other 110 observations, infections syndrome (septicemia due to gram-negative rods above all) was treated by an early and intensive combination antibiotherapy (three successive protocols are employed, after failure of the precedent), in association with a careful medical reanimation and trasfusions of granulocytes in 16 cases. Regression was obtained in 94 cases (59,5%) but infection was lethal in 16 patients (10.1%). More than cytological variety of AL, principal pronostic element is age (15 deaths among 88 infections episodes in adults, one among 22 in children). Granulocytes rate at the time of aplasia (lower than 500 /mm3) also represents a factor of gravity. Among 94 infections episodes, antibiotherapy was successful alone in 81 cases (86.2%), illustrating the fundamental place of this treatment."}
{"id": "PMID:224481", "title": "[Value and technique of measuring the tibia length in pathological conditions of the newborn (author's transl)].", "content": "Together with determining the bone age of the immature and/or small-for date neonate, it is possible to work out the length of the tibia on the profile X ray of the leg. Authors have drafted up a scale of growth, featuring the 10 th, 50 th and 90 th percentiles common for boys and girls ranging from 28 to 42 weeks of gestation and they propose this new criterion for the study of pathological neonates, particularly the small-for-date. The method has a second advantage: it is possible to follow the increment of the tibia length by X rays taken at regular intervals and thus to estimate the various factors that can interfere with the child's growth, and in the first place, the quality of the food given to the child.", "contents": "[Value and technique of measuring the tibia length in pathological conditions of the newborn (author's transl)]. Together with determining the bone age of the immature and/or small-for date neonate, it is possible to work out the length of the tibia on the profile X ray of the leg. Authors have drafted up a scale of growth, featuring the 10 th, 50 th and 90 th percentiles common for boys and girls ranging from 28 to 42 weeks of gestation and they propose this new criterion for the study of pathological neonates, particularly the small-for-date. The method has a second advantage: it is possible to follow the increment of the tibia length by X rays taken at regular intervals and thus to estimate the various factors that can interfere with the child's growth, and in the first place, the quality of the food given to the child."}
{"id": "PMID:224483", "title": "[Myoclonus during a treatment with diclofenac (author's transl)].", "content": "Diclofenac is a non stero\u00efdal anti-inflammatory drug. In 1978, the case of a myoclonic encephalopathy appearing three days after starting a treatment with this drug in a patients with renal insufficiency was published. A few months later, we observed a case of myoclonus of the lower limbs in a young man in good general status, without renal insufficiency, after four full months of this treatment. Myoclonus vanished 48 hours after withdrawal of the drug.", "contents": "[Myoclonus during a treatment with diclofenac (author's transl)]. Diclofenac is a non stero\u00efdal anti-inflammatory drug. In 1978, the case of a myoclonic encephalopathy appearing three days after starting a treatment with this drug in a patients with renal insufficiency was published. A few months later, we observed a case of myoclonus of the lower limbs in a young man in good general status, without renal insufficiency, after four full months of this treatment. Myoclonus vanished 48 hours after withdrawal of the drug."}
{"id": "PMID:224482", "title": "[Value of the antibiogram technic for the treatment of urogenital infection with Ureaplasma (author's transl)].", "content": "We have currently established the spectrum of sensitivity of the isolated strains to various antibiotics before prescribing the appropriate treatment. A microtechnic has been used. The most active antibiotics are: minocyclin, pristinamycin, erythromycin, chloramphenicol, oxytetracyclin, kanamycin, tobramycin, streptomycin, in this order.", "contents": "[Value of the antibiogram technic for the treatment of urogenital infection with Ureaplasma (author's transl)]. We have currently established the spectrum of sensitivity of the isolated strains to various antibiotics before prescribing the appropriate treatment. A microtechnic has been used. The most active antibiotics are: minocyclin, pristinamycin, erythromycin, chloramphenicol, oxytetracyclin, kanamycin, tobramycin, streptomycin, in this order."}
{"id": "PMID:224485", "title": "[Menetrier's disease and edematous syndrome (author's transl)].", "content": "The authors report a case of Menetrier's disease revealed in a 51 years woman before oedomas by systematic gastroscopy. Somes particularities of this case authorize to argue problems put by this disease: a thyroid nodule treated by L + triodothyronin; an eosinophilia; a biological study of gastric secretion, gastrin and intrinsec factor level; an hormonal, immunologic and genetic exploration; an histochimic and ultra-structural study of operative portion; its favorable evolution after total gastrectomy.", "contents": "[Menetrier's disease and edematous syndrome (author's transl)]. The authors report a case of Menetrier's disease revealed in a 51 years woman before oedomas by systematic gastroscopy. Somes particularities of this case authorize to argue problems put by this disease: a thyroid nodule treated by L + triodothyronin; an eosinophilia; a biological study of gastric secretion, gastrin and intrinsec factor level; an hormonal, immunologic and genetic exploration; an histochimic and ultra-structural study of operative portion; its favorable evolution after total gastrectomy."}
{"id": "PMID:224486", "title": "[Williams and Beuren's syndrome with hypertension and associated renal abnormalities (author's transl)].", "content": "The authors presented a case of the Williams and Beuren's syndrome, special by the existence of aorta coarctation, high blood pressure, nephrotic syndrome and renal dysplasia. The Williams-Beuren's syndrome is characterised by the association of facial anomalies, mental retardation and supra-valvular aortic stenosis. The case presented in this study demonstrates: -- the symptomatic diversity of the Williams and Beuren's syndrome; -- and the relationship of this syndrome and severe idiopathic hypercalcemia of the infant. The etiopathogenesis is also discussed.", "contents": "[Williams and Beuren's syndrome with hypertension and associated renal abnormalities (author's transl)]. The authors presented a case of the Williams and Beuren's syndrome, special by the existence of aorta coarctation, high blood pressure, nephrotic syndrome and renal dysplasia. The Williams-Beuren's syndrome is characterised by the association of facial anomalies, mental retardation and supra-valvular aortic stenosis. The case presented in this study demonstrates: -- the symptomatic diversity of the Williams and Beuren's syndrome; -- and the relationship of this syndrome and severe idiopathic hypercalcemia of the infant. The etiopathogenesis is also discussed."}
{"id": "PMID:224484", "title": "[Thrombocytosis: general frequency and etiological circumstances (author's transl)].", "content": "During a period of five years, fifteen thousand platelet counts has been systematically realised at the H\u00f4tel-Dieu Hospital in Marseilles. A thrombocytosis superior to 400 000/mm3 has been observed in 1,2% of cases, in such various etiological cases as mainly cancer (30%), infectious diseases (28%) and post-hemorragic anaemias (11%).", "contents": "[Thrombocytosis: general frequency and etiological circumstances (author's transl)]. During a period of five years, fifteen thousand platelet counts has been systematically realised at the H\u00f4tel-Dieu Hospital in Marseilles. A thrombocytosis superior to 400 000/mm3 has been observed in 1,2% of cases, in such various etiological cases as mainly cancer (30%), infectious diseases (28%) and post-hemorragic anaemias (11%)."}
{"id": "PMID:224487", "title": "[Sarcoidosis and portal hypertension (author's transl)].", "content": "A new case of portal hypertension associated with hepatic sarco\u00efdosis is reported. The authors reviewed 23 other cases in the literature, they underline diagnostic difficulties of which the etiology remains unclear. Surgical treatment seems to be the best in comparison with corticotherapy. Postoperative encephalopathy may appear till 8 years postoperatively. Hepatic atrophy rather than sarco\u00efdosis must be responsible for it.", "contents": "[Sarcoidosis and portal hypertension (author's transl)]. A new case of portal hypertension associated with hepatic sarco\u00efdosis is reported. The authors reviewed 23 other cases in the literature, they underline diagnostic difficulties of which the etiology remains unclear. Surgical treatment seems to be the best in comparison with corticotherapy. Postoperative encephalopathy may appear till 8 years postoperatively. Hepatic atrophy rather than sarco\u00efdosis must be responsible for it."}
{"id": "PMID:224489", "title": "[Diagnostic problems in gastric dysplasias: value of cytology (author's transl)].", "content": "Gastric smears have been performed on 835 patients, among which examinations 771 (92 percent) were available. Histology assumed in parallel showed a dysplasia lesion in 56 cases: 14 of the 601 negative smears (2.3 percent), in 33 of the 40 suspect smears (82 percent), and in 9 of the 130 cases of positive smears (7 percent). Gastric dysplasia evidence both by cytology and pathology show mostly differenciated cells, alterations of which reflect the lesion level. By contrast, cytology and histology diagnosis are not in agreement when dysplasia concern dedifferenciated cells with a severe degree of alterations which can be misinterpreted as malignant cells.", "contents": "[Diagnostic problems in gastric dysplasias: value of cytology (author's transl)]. Gastric smears have been performed on 835 patients, among which examinations 771 (92 percent) were available. Histology assumed in parallel showed a dysplasia lesion in 56 cases: 14 of the 601 negative smears (2.3 percent), in 33 of the 40 suspect smears (82 percent), and in 9 of the 130 cases of positive smears (7 percent). Gastric dysplasia evidence both by cytology and pathology show mostly differenciated cells, alterations of which reflect the lesion level. By contrast, cytology and histology diagnosis are not in agreement when dysplasia concern dedifferenciated cells with a severe degree of alterations which can be misinterpreted as malignant cells."}
{"id": "PMID:224488", "title": "[Clinical trial of Pulvo 47 Neomycin in the treatment of leg ulcer (author's transl)].", "content": "Pulva 47 Neomycine was tested in 30 patients suffering from a leg ulcer, 11 of those were surinfected. Half the ulcers dated back over 6 months. The would preparation included a careful cleaning with a permanganate or dakin's solution. In most of the cases, the product was applied on a once a day basis during an average period of 30 days. In 12 patients, the severity of the infection needed an additional antibiotherapy administered orally. The results were expressed in relation to the activity on the infection and wound healing. In 28 patients, the signs of infection disappeared completely. The wound healing effect was very satisfying in 22 patients (19 of them had varicose or post-phlebitis ulcers). The value of the results is independent on the date of onset and on the area of the lesions. The tolerance was good; only 4 patients suffered from itching after the application of the compound. It is mainly through his wound healing effect that Pulvo 47 Neomycine represents a progress compared to other similar specialties.", "contents": "[Clinical trial of Pulvo 47 Neomycin in the treatment of leg ulcer (author's transl)]. Pulva 47 Neomycine was tested in 30 patients suffering from a leg ulcer, 11 of those were surinfected. Half the ulcers dated back over 6 months. The would preparation included a careful cleaning with a permanganate or dakin's solution. In most of the cases, the product was applied on a once a day basis during an average period of 30 days. In 12 patients, the severity of the infection needed an additional antibiotherapy administered orally. The results were expressed in relation to the activity on the infection and wound healing. In 28 patients, the signs of infection disappeared completely. The wound healing effect was very satisfying in 22 patients (19 of them had varicose or post-phlebitis ulcers). The value of the results is independent on the date of onset and on the area of the lesions. The tolerance was good; only 4 patients suffered from itching after the application of the compound. It is mainly through his wound healing effect that Pulvo 47 Neomycine represents a progress compared to other similar specialties."}
{"id": "PMID:224490", "title": "[Learning disabilities (author's transl)].", "content": "The author insists on the necessity to set the learning disabilities of written language in the frame of the child's personality and of the family and school environment. A therapeutical intervening which would not take these data into consideration risks to \"crystallise\" the parents in an attitude which excludes the coming to them of their responsibilities in the child's difficulties.", "contents": "[Learning disabilities (author's transl)]. The author insists on the necessity to set the learning disabilities of written language in the frame of the child's personality and of the family and school environment. A therapeutical intervening which would not take these data into consideration risks to \"crystallise\" the parents in an attitude which excludes the coming to them of their responsibilities in the child's difficulties."}
{"id": "PMID:224491", "title": "[Human cysticercosis. Four cases. (second part) (author's transl)].", "content": "Beside the principal aspects of cysticercosis (see the first part of this article) there are others clinical forms : medullar, ocular, subcutaneous, often associated to cerebral cysticercosis, latent or not. The complemental investigations are numerous, their value is variable. The complemental investigations are numerous, their value is variable. It is often difficult to distinguish cysticercosis from cenurosis. Therapy remains deceitful. Very important and useful are the measures of prevention.", "contents": "[Human cysticercosis. Four cases. (second part) (author's transl)]. Beside the principal aspects of cysticercosis (see the first part of this article) there are others clinical forms : medullar, ocular, subcutaneous, often associated to cerebral cysticercosis, latent or not. The complemental investigations are numerous, their value is variable. The complemental investigations are numerous, their value is variable. It is often difficult to distinguish cysticercosis from cenurosis. Therapy remains deceitful. Very important and useful are the measures of prevention."}
{"id": "PMID:224492", "title": "[Cutis verticis gyrata, hypertrophic gastritis, motrice diarhea, and horse's tall syndrome, a new association an apudoma (carcinoid or chemodectoma) (author's transl)].", "content": "The authors report the observation of a 70 years male with Cutis Verticis Gyrata (without hypertrophying osteopathy), Menetrier's hypertrophic gastritis, motrice diarrhea of the endocrine type, flush syndrom, liver angiomatosis and a large sacral water clear cells tumor with horse's tail syndrom. The initial tumor was on the posterior wall of rectum, but was necrosed : bone metastasing chemodectoma, or locally invading carcinoid ? This new complex paraneoplastic disease seems to be associated with APUD tumor.", "contents": "[Cutis verticis gyrata, hypertrophic gastritis, motrice diarhea, and horse's tall syndrome, a new association an apudoma (carcinoid or chemodectoma) (author's transl)]. The authors report the observation of a 70 years male with Cutis Verticis Gyrata (without hypertrophying osteopathy), Menetrier's hypertrophic gastritis, motrice diarrhea of the endocrine type, flush syndrom, liver angiomatosis and a large sacral water clear cells tumor with horse's tail syndrom. The initial tumor was on the posterior wall of rectum, but was necrosed : bone metastasing chemodectoma, or locally invading carcinoid ? This new complex paraneoplastic disease seems to be associated with APUD tumor."}
{"id": "PMID:224493", "title": "[Consumption coagulopathy in adenocarcinomas. Report of seven cases (author's transl)].", "content": "The authors present 7 cases of disseminated intravascular coagulation (DIC), 4 of them with hemorragic syndrom, with appeared in the course of different adenocarcinomas (prostatic, pancreatic or undeterminated). Emphasis is set on 2 points : -- in all cases, metastasis of these cancers can be found in the bone marrow and/or the liver ; -- DIC may be the first sign of the disease. The pronostic is very bad, even with heparinic therapy because of the lack of specific treatment but for prostatic cancer.", "contents": "[Consumption coagulopathy in adenocarcinomas. Report of seven cases (author's transl)]. The authors present 7 cases of disseminated intravascular coagulation (DIC), 4 of them with hemorragic syndrom, with appeared in the course of different adenocarcinomas (prostatic, pancreatic or undeterminated). Emphasis is set on 2 points : -- in all cases, metastasis of these cancers can be found in the bone marrow and/or the liver ; -- DIC may be the first sign of the disease. The pronostic is very bad, even with heparinic therapy because of the lack of specific treatment but for prostatic cancer."}
{"id": "PMID:224494", "title": "[Secretan's disease (author's transl)].", "content": "Five cases are presented of hard, brawny, edema of the dorsum of the hand. Surgical interventions was doing in two cases, but the results were poor with persistent pain. We now believe splinting and active exercise to be the initial treatment of choice. Secretan's disease produces a quite extensive disability of the hand which lasted more than 6 months, often for years.", "contents": "[Secretan's disease (author's transl)]. Five cases are presented of hard, brawny, edema of the dorsum of the hand. Surgical interventions was doing in two cases, but the results were poor with persistent pain. We now believe splinting and active exercise to be the initial treatment of choice. Secretan's disease produces a quite extensive disability of the hand which lasted more than 6 months, often for years."}
{"id": "PMID:224495", "title": "[Wilson's disease. A clinical and pathological study on 6 cases (author's transl)].", "content": "In connection with 6 cases of Wilson's disease, the authors recall the main features of this hereditary metabolic disorder at late onset (usually the second decade), treatable with a chelating agent, when diagnosed at an early stage. Wilson's disease is first of all a liver disease and the authors emphasize the fact that cirrhosis is usually present when neurologic symptoms, revealing the disease in 5 cases, appear, even if there is no clinical or biological evidence for liver disease. In one instance hemolytic anemia and chronic active hepatitis were observed at clinical onset. Copper metabolism usually gives the key for diagnosis but its interpretation may be difficult, a normal serum ceruleoplasmin level being found in two patients and evaluated at 6% in the literature. This fact brings up the puzzling question of the pathogesis of the disease. Wilson's disease is not a simple ceruleoplasmin synthesis defect, but a lysosomal disease responsible for the lack of copper biliary excretion. This is pointed out by histochemical studies using a special rubeanic acid preparation (revealing copper deposit on the biliary side of the hepatic cell), and by electron microscopy showing lysosomal dystrophy.", "contents": "[Wilson's disease. A clinical and pathological study on 6 cases (author's transl)]. In connection with 6 cases of Wilson's disease, the authors recall the main features of this hereditary metabolic disorder at late onset (usually the second decade), treatable with a chelating agent, when diagnosed at an early stage. Wilson's disease is first of all a liver disease and the authors emphasize the fact that cirrhosis is usually present when neurologic symptoms, revealing the disease in 5 cases, appear, even if there is no clinical or biological evidence for liver disease. In one instance hemolytic anemia and chronic active hepatitis were observed at clinical onset. Copper metabolism usually gives the key for diagnosis but its interpretation may be difficult, a normal serum ceruleoplasmin level being found in two patients and evaluated at 6% in the literature. This fact brings up the puzzling question of the pathogesis of the disease. Wilson's disease is not a simple ceruleoplasmin synthesis defect, but a lysosomal disease responsible for the lack of copper biliary excretion. This is pointed out by histochemical studies using a special rubeanic acid preparation (revealing copper deposit on the biliary side of the hepatic cell), and by electron microscopy showing lysosomal dystrophy."}
{"id": "PMID:224496", "title": "[Surgical treatment of Prinzmetal's syndrome. Report of sixty operated cases (author's transl)].", "content": "The results of the surgical treatment of Prinzmetal's angina are reported in this study of 60 patients. The operative mortality is 3,3 percent and the incidence of post-operative infarction is 20 percent. 53 patients were followed over an average period of 2,7 years. The global survival rate is 91 percent at 5 years, the infarction rate is 24 percent. 76 percent of the sublims are asymptomac. The patients can be classified in three group : isolated lesions, multiple lesions and spasms.", "contents": "[Surgical treatment of Prinzmetal's syndrome. Report of sixty operated cases (author's transl)]. The results of the surgical treatment of Prinzmetal's angina are reported in this study of 60 patients. The operative mortality is 3,3 percent and the incidence of post-operative infarction is 20 percent. 53 patients were followed over an average period of 2,7 years. The global survival rate is 91 percent at 5 years, the infarction rate is 24 percent. 76 percent of the sublims are asymptomac. The patients can be classified in three group : isolated lesions, multiple lesions and spasms."}
{"id": "PMID:224497", "title": "[Study of an homogeneous population of obeses people and of its regression of weight under hypocaloric diet in hospital. II. - Weight loss (author's transl)].", "content": "A study of 79 obese patients who were hospitalized and treated with a low calorie diet demonstrated that the weight loss occurred in a univocal manner, according to a semilogarithmic law. It was not influenced, as far as initial results were concerned, by the age, sex, or morphotype of the patient, or whether weight gain was recent or of long-standing. Factors affecting results, however, are the existence of functional signs, the amount of natriuresis during the first few days, and the quantity of alcohol ingested regularly. Short term results, one month after leaving hospital, appear to be moderate only. A diet supplying 800 calories causes weight loss at the expense of body fat. Individual variations in minimal calorie requirements during the treatment can be used as a basis for prescribing a personalized supplementary diet.", "contents": "[Study of an homogeneous population of obeses people and of its regression of weight under hypocaloric diet in hospital. II. - Weight loss (author's transl)]. A study of 79 obese patients who were hospitalized and treated with a low calorie diet demonstrated that the weight loss occurred in a univocal manner, according to a semilogarithmic law. It was not influenced, as far as initial results were concerned, by the age, sex, or morphotype of the patient, or whether weight gain was recent or of long-standing. Factors affecting results, however, are the existence of functional signs, the amount of natriuresis during the first few days, and the quantity of alcohol ingested regularly. Short term results, one month after leaving hospital, appear to be moderate only. A diet supplying 800 calories causes weight loss at the expense of body fat. Individual variations in minimal calorie requirements during the treatment can be used as a basis for prescribing a personalized supplementary diet."}
{"id": "PMID:224499", "title": "[Vertebro-basilar dissecting aneurysm : an anatomo-clinical case study fibrodysplasia of the left vertebral artery (author's transl)].", "content": "A new anatomo-clinical case of vertebro-basilar dissecting aneurysm in a 43 year old woman is reported. The originality of this study comes from the autopsic discovery of an intimal fibro-dysplasia at the origin of the dissection in the left vertebral artery. The authors also included anatomoclinical and pathogenic comments about both the lesions discussed.", "contents": "[Vertebro-basilar dissecting aneurysm : an anatomo-clinical case study fibrodysplasia of the left vertebral artery (author's transl)]. A new anatomo-clinical case of vertebro-basilar dissecting aneurysm in a 43 year old woman is reported. The originality of this study comes from the autopsic discovery of an intimal fibro-dysplasia at the origin of the dissection in the left vertebral artery. The authors also included anatomoclinical and pathogenic comments about both the lesions discussed."}
{"id": "PMID:224500", "title": "[Glomerular disease associated with myelofibrosis (author's transl)].", "content": "The authors report the case of a 46 year-old patient presenting with membranous-proliferative glomerular disease, megakaryocytes present in the glomerular capillaries, evolving concomitantly with myelofibrosis. There are two possible explanations for this unusual association: the glomerular disease and the myelofibrosis may both result from the same etiologic and pathogenic factor, or the glomerular disease may be the consequence, thrombocytosis existing, of platelet activation, either direct or after deposition of immune complexes. The formation of immune complexes after antigenic stimulation in myelofibrosis is theoretically compatible with immunitary anomalies found in the evolution of this disorder as described in the literature.", "contents": "[Glomerular disease associated with myelofibrosis (author's transl)]. The authors report the case of a 46 year-old patient presenting with membranous-proliferative glomerular disease, megakaryocytes present in the glomerular capillaries, evolving concomitantly with myelofibrosis. There are two possible explanations for this unusual association: the glomerular disease and the myelofibrosis may both result from the same etiologic and pathogenic factor, or the glomerular disease may be the consequence, thrombocytosis existing, of platelet activation, either direct or after deposition of immune complexes. The formation of immune complexes after antigenic stimulation in myelofibrosis is theoretically compatible with immunitary anomalies found in the evolution of this disorder as described in the literature."}
{"id": "PMID:224501", "title": "[Perforation of rectal with peritonitis during a barium enema administration. Report of a case (author's transl)].", "content": "The authors report one case of perforation of rectal with peritonitis during a barium enema administration in a patient suffering from an adeno-carcinome of colon, and died after 48 hours with collapsus. After a brief review of the literature, the authors expose pathogeny and clinical signs of this relatively rare accidients. The conclusions repose on watchful precautions according to indications and technical way of barium enema examination in patients specially exposed to perforation accidents.", "contents": "[Perforation of rectal with peritonitis during a barium enema administration. Report of a case (author's transl)]. The authors report one case of perforation of rectal with peritonitis during a barium enema administration in a patient suffering from an adeno-carcinome of colon, and died after 48 hours with collapsus. After a brief review of the literature, the authors expose pathogeny and clinical signs of this relatively rare accidients. The conclusions repose on watchful precautions according to indications and technical way of barium enema examination in patients specially exposed to perforation accidents."}
{"id": "PMID:224502", "title": "[Scattered arterioveinous fistulae of the lung associated with alcoholic cirrhosis : about one case complicated by neurological involvement (author's transl)].", "content": "We report case of 49 years old woman suffering from severe alcoholic cirrhosis and presenting arterioveinous fistulae of the lung which evidence was given by selective arteriography. Quantitative analysis of vasoactive intestinal polypeptide show no modification ; mecanism of the opening of fistulae could no be found. This observation is noteworthy in consideration of lung lasting evolution (4 years) and out come of neurological complication (must likely due to cortical phlebitis).", "contents": "[Scattered arterioveinous fistulae of the lung associated with alcoholic cirrhosis : about one case complicated by neurological involvement (author's transl)]. We report case of 49 years old woman suffering from severe alcoholic cirrhosis and presenting arterioveinous fistulae of the lung which evidence was given by selective arteriography. Quantitative analysis of vasoactive intestinal polypeptide show no modification ; mecanism of the opening of fistulae could no be found. This observation is noteworthy in consideration of lung lasting evolution (4 years) and out come of neurological complication (must likely due to cortical phlebitis)."}
{"id": "PMID:224498", "title": "[Detection and follow up of inflammatory lesions of the central nervous system by means of cytological study of the cerebrospinal fluid (author's transl)].", "content": "Cytocentrifugation gives an excellent quantitative and qualitative preservation of the cerebrospinal fluid cells. This method permits the study various types of meningeal or ventricular inflammatory changes (acute inflammatory changes with granulocytes, immunitary type or macrophagic changes) and causal diagnosis. During meningitis following bleeding or neurosurgical operation, repeated cytological examinations allow a simple but useful follow up of the evolution during the treatment.", "contents": "[Detection and follow up of inflammatory lesions of the central nervous system by means of cytological study of the cerebrospinal fluid (author's transl)]. Cytocentrifugation gives an excellent quantitative and qualitative preservation of the cerebrospinal fluid cells. This method permits the study various types of meningeal or ventricular inflammatory changes (acute inflammatory changes with granulocytes, immunitary type or macrophagic changes) and causal diagnosis. During meningitis following bleeding or neurosurgical operation, repeated cytological examinations allow a simple but useful follow up of the evolution during the treatment."}
{"id": "PMID:224503", "title": "[Therapeutic indications of Cortalugel 20 in hepatic and gastro-enterological diseases (author's transl)].", "content": "Regular observation of 40 patients treated with Cortalugel 20 confirmed that the association of aluminum phosphate with prednisolone produced no phenomenon of chelation and did not affect absorption of the latter compound. The product was well-tolerated by the digestive system during prolonged administration for the treatment of hepatic and gastro-enterological diseases for which corticotherapy is usually administered.", "contents": "[Therapeutic indications of Cortalugel 20 in hepatic and gastro-enterological diseases (author's transl)]. Regular observation of 40 patients treated with Cortalugel 20 confirmed that the association of aluminum phosphate with prednisolone produced no phenomenon of chelation and did not affect absorption of the latter compound. The product was well-tolerated by the digestive system during prolonged administration for the treatment of hepatic and gastro-enterological diseases for which corticotherapy is usually administered."}
{"id": "PMID:224509", "title": "Isolated accessory nerve palsy.", "content": "Accessory nerve palsy is either idiopathic or secondary to local trauma, infection, or tumor. The discomfort and disability produced as a result of trapezius weakness may be significant. The clinical features and management of accessory nerve palsy have been discussed.", "contents": "Isolated accessory nerve palsy. Accessory nerve palsy is either idiopathic or secondary to local trauma, infection, or tumor. The discomfort and disability produced as a result of trapezius weakness may be significant. The clinical features and management of accessory nerve palsy have been discussed."}
{"id": "PMID:224505", "title": "[Sudden death in new-born babies (author's transl)].", "content": "This sudden death of a new-born baby, which had been thriving up to then, is a dramatic but not exceptional event. A systematic search for the etiology must be made, and this should include an autopsy in order that the diagnosis of \"sudden and unexplained death\" is confirmed only after eliminating all other possible causes. Knowledge of this syndrome has benefited from epidemiological surveys which have defined the previous clinical condition, but none of the many etiollotical hypotheses envisaged can take into account the total number of cases reported. One of the most recent cases developed apnoea during sleep, which could explain some unexpected deaths in new-born babies. This was discovered by polygraphic sleep recordings and confirmed by pathological examinations. These demonstrated indirect signs of chronic hypoxia which could have been related to the sudden death of the baby. Though there does not appear to be any relationship between the apnoea syndrome during sleep and these sudden  and unexpected deaths, this hypothesis has opened up a new promising line of research which could help to identify new-born babies at risk from \"sudden death\", and to propose preventative measures.", "contents": "[Sudden death in new-born babies (author's transl)]. This sudden death of a new-born baby, which had been thriving up to then, is a dramatic but not exceptional event. A systematic search for the etiology must be made, and this should include an autopsy in order that the diagnosis of \"sudden and unexplained death\" is confirmed only after eliminating all other possible causes. Knowledge of this syndrome has benefited from epidemiological surveys which have defined the previous clinical condition, but none of the many etiollotical hypotheses envisaged can take into account the total number of cases reported. One of the most recent cases developed apnoea during sleep, which could explain some unexpected deaths in new-born babies. This was discovered by polygraphic sleep recordings and confirmed by pathological examinations. These demonstrated indirect signs of chronic hypoxia which could have been related to the sudden death of the baby. Though there does not appear to be any relationship between the apnoea syndrome during sleep and these sudden  and unexpected deaths, this hypothesis has opened up a new promising line of research which could help to identify new-born babies at risk from \"sudden death\", and to propose preventative measures."}
{"id": "PMID:224504", "title": "[Listeriosis : evaluation of twenty years of inquires at Rouen (France) (author's transl)].", "content": "The laboratory of bacteriology of the CHU of Rouen has isolated in twenty years 297 strains of Listeria monocytogenes which are corresponding to 249 cases, 48 new-borns being infected by the same germ as their mother. The listeriosis frequency is increasing ; the disease is recurrent, with a periodicity of four years, but the number of the cases which are observed every year is larger than that which has been observed four years before. The disease seems to affect mainly the women ; in reality, both sexes are sensitive, but some conditions, especially the pregnancy, are favouring the disease burst. Five pregnant women per one thousand incur the risk to catch a listeriosis during their pregnancy ; for want of early diagnosis and treatment, they will not be able to carry their pregnancy through, and will generally give birth to shortly condemned children.", "contents": "[Listeriosis : evaluation of twenty years of inquires at Rouen (France) (author's transl)]. The laboratory of bacteriology of the CHU of Rouen has isolated in twenty years 297 strains of Listeria monocytogenes which are corresponding to 249 cases, 48 new-borns being infected by the same germ as their mother. The listeriosis frequency is increasing ; the disease is recurrent, with a periodicity of four years, but the number of the cases which are observed every year is larger than that which has been observed four years before. The disease seems to affect mainly the women ; in reality, both sexes are sensitive, but some conditions, especially the pregnancy, are favouring the disease burst. Five pregnant women per one thousand incur the risk to catch a listeriosis during their pregnancy ; for want of early diagnosis and treatment, they will not be able to carry their pregnancy through, and will generally give birth to shortly condemned children."}
{"id": "PMID:224511", "title": "Granular cell myoblastoma of the esophagus after irradiation for carcinoma.", "content": "Granular cell myoblastoma is an uncommon, usually benign tumor. Only 20 cases are reported in the esophagus. We describe a 65-year-old woman who developed a granular cell myoblastoma of the postericoid esophagus in the area of a squamous cell carcinoma successfully treated with irradiation. To our knowledge, this is the 21st reported case, and the only case occurring in the esophagus after irradiation for primary squamous cell carcinoma.", "contents": "Granular cell myoblastoma of the esophagus after irradiation for carcinoma. Granular cell myoblastoma is an uncommon, usually benign tumor. Only 20 cases are reported in the esophagus. We describe a 65-year-old woman who developed a granular cell myoblastoma of the postericoid esophagus in the area of a squamous cell carcinoma successfully treated with irradiation. To our knowledge, this is the 21st reported case, and the only case occurring in the esophagus after irradiation for primary squamous cell carcinoma."}
{"id": "PMID:224517", "title": "Do methoxyflurane and enflurane induce hepatic drug-metabolizing enzymes?", "content": "The effect of acute anaesthetic (1,0 MAC) and chronic subanaesthetic (0,1 MAC) exposure to methoxyflurane and enflurane on the levels of several liver enzymes is reported. Methoxyflurane appears to be an enzyme-inducing agent similar to spironolactone, whereas enflurane does not appear to be an inducing agent for any of the enzymes studied.", "contents": "Do methoxyflurane and enflurane induce hepatic drug-metabolizing enzymes? The effect of acute anaesthetic (1,0 MAC) and chronic subanaesthetic (0,1 MAC) exposure to methoxyflurane and enflurane on the levels of several liver enzymes is reported. Methoxyflurane appears to be an enzyme-inducing agent similar to spironolactone, whereas enflurane does not appear to be an inducing agent for any of the enzymes studied."}
{"id": "PMID:224518", "title": "Bernard, Mitchell, Horner syndrome and others?", "content": "Recent findings of parasellar sympathetic connections lead to renewed speculation concerning the ultimate course of the orbital and facial sympathetic pathways.", "contents": "Bernard, Mitchell, Horner syndrome and others? Recent findings of parasellar sympathetic connections lead to renewed speculation concerning the ultimate course of the orbital and facial sympathetic pathways."}
{"id": "PMID:224521", "title": "Aggregation of gel-filtered guinea-pig platelets by lipoproteins.", "content": "Very low density lipoproteins (VLDL) and low density lipoproteins (LDL) were isolated from serum of hypercholesterolemic guinea-pigs, and the effect of these lipoproteins on guinea-pig platelets was studied. VLDL (greater than 100 microgram/ml) and LDL (greater than 400 microgram/ml) were found to cause aggregation of gel-filtered platelets (GFP), although the extent of GFP aggregation by LDL was smaller than that by VLDL. In platelet-rich plasma, however, lipoproteins could not induce platelet aggregation. VLDL and LDL even at the low concentrations at which lipoproteins alone could not induce aggregation potentiated ADP-induced aggregation of GFP. VLDL-induced aggregation of GFP was inhibited by apyrase (0.2--1.0 mg/ml) in a concentration-related manner. Prostaglandin E1, dipyridamole, potassium cyanide and ethylenediaminetetraacetic acid inhibited VLDL- and ADP-induced aggregation of GFP in the almost same degree. Inhibitions of VLDL-induced GFP aggregation by acetylsalicylic acid and albumin were slightly stronger than that of ADP-induced aggregation. These findings suggest that lipoproteins modulate platelets so that endogenous ADP can be released from platelets.", "contents": "Aggregation of gel-filtered guinea-pig platelets by lipoproteins. Very low density lipoproteins (VLDL) and low density lipoproteins (LDL) were isolated from serum of hypercholesterolemic guinea-pigs, and the effect of these lipoproteins on guinea-pig platelets was studied. VLDL (greater than 100 microgram/ml) and LDL (greater than 400 microgram/ml) were found to cause aggregation of gel-filtered platelets (GFP), although the extent of GFP aggregation by LDL was smaller than that by VLDL. In platelet-rich plasma, however, lipoproteins could not induce platelet aggregation. VLDL and LDL even at the low concentrations at which lipoproteins alone could not induce aggregation potentiated ADP-induced aggregation of GFP. VLDL-induced aggregation of GFP was inhibited by apyrase (0.2--1.0 mg/ml) in a concentration-related manner. Prostaglandin E1, dipyridamole, potassium cyanide and ethylenediaminetetraacetic acid inhibited VLDL- and ADP-induced aggregation of GFP in the almost same degree. Inhibitions of VLDL-induced GFP aggregation by acetylsalicylic acid and albumin were slightly stronger than that of ADP-induced aggregation. These findings suggest that lipoproteins modulate platelets so that endogenous ADP can be released from platelets."}
{"id": "PMID:224522", "title": "Mode of action of ticlopidine in inhibition of platelet aggregation in the rat.", "content": "Ticlopidine, when orally administered to rats, resulted in activation of basal and prostaglandin E1 (PGE1)-stimulated adenylate cylase activity through increase in affinity of the cyclase in platelet membrane to PGE1, although it failed to affect adenosine- or sodium fluoride-stimulated activity of the enzyme. In washed platelets, Ticlopidine also activated basal and PGE1-stimulated activity of the cyclase and prevented reduction in the cyclase activity caused by low concentrations of PGE2. Furthermore, Ticlopidine inhibited malondialdehyde formation in platelets induced by thrombin but failed to inhibit that caused by exogenous arachidonic acid. Adenosine 3',5'-cyclic monophosphate (c-AMP): phosphodiesterase activity of platelet lysate was not significantly affected by Ticlopidine treatment. These findings indicate that Ticlopidine inhibits platelet aggregation and prostaglandin synthesis from endogenous substrate through activating basal and PGE1-stimulated activity of the cyclase, preventing PGE2-induced depression of the cyclase activity and thus increasing platelet c-AMP level.", "contents": "Mode of action of ticlopidine in inhibition of platelet aggregation in the rat. Ticlopidine, when orally administered to rats, resulted in activation of basal and prostaglandin E1 (PGE1)-stimulated adenylate cylase activity through increase in affinity of the cyclase in platelet membrane to PGE1, although it failed to affect adenosine- or sodium fluoride-stimulated activity of the enzyme. In washed platelets, Ticlopidine also activated basal and PGE1-stimulated activity of the cyclase and prevented reduction in the cyclase activity caused by low concentrations of PGE2. Furthermore, Ticlopidine inhibited malondialdehyde formation in platelets induced by thrombin but failed to inhibit that caused by exogenous arachidonic acid. Adenosine 3',5'-cyclic monophosphate (c-AMP): phosphodiesterase activity of platelet lysate was not significantly affected by Ticlopidine treatment. These findings indicate that Ticlopidine inhibits platelet aggregation and prostaglandin synthesis from endogenous substrate through activating basal and PGE1-stimulated activity of the cyclase, preventing PGE2-induced depression of the cyclase activity and thus increasing platelet c-AMP level."}
{"id": "PMID:224525", "title": "[High density lipoproteins dissociation induced by addition of delta 9-THC (author's transl)].", "content": "Delta 9-THC has a structure similar to cholesterol and can be associated to different lipoproteins of the serum. This study concerns the in vitro association of (3H) delta 9-THC with human HDL (1,10 less than 1,19 g/ml). The incubation (1 hour at 37 degrees C) of (3H) delta 9-THC with HDL induces dissociation of HDL into 3 subunits which are characterized by different electrophoretic migration. Immunoelectrophoresis reveals that the slower migrating fraction, poor in lipids, is mainly apo A1; the faster migrating fraction is similar to native HDL; the intermediate migration fraction, rich in lipids, contains mainly C peptides. Two dimensional immuneolectrophoresis confirms these results. These effects could explain the modifications of cells membranes observed in serum of people smoking marihuana.", "contents": "[High density lipoproteins dissociation induced by addition of delta 9-THC (author's transl)]. Delta 9-THC has a structure similar to cholesterol and can be associated to different lipoproteins of the serum. This study concerns the in vitro association of (3H) delta 9-THC with human HDL (1,10 less than 1,19 g/ml). The incubation (1 hour at 37 degrees C) of (3H) delta 9-THC with HDL induces dissociation of HDL into 3 subunits which are characterized by different electrophoretic migration. Immunoelectrophoresis reveals that the slower migrating fraction, poor in lipids, is mainly apo A1; the faster migrating fraction is similar to native HDL; the intermediate migration fraction, rich in lipids, contains mainly C peptides. Two dimensional immuneolectrophoresis confirms these results. These effects could explain the modifications of cells membranes observed in serum of people smoking marihuana."}
{"id": "PMID:224531", "title": "Hepatic effects of xylidine isomers in rats.", "content": "The effect of repeated (4 weeks) oral administration of 2,4-, 2,5- or 2,6-xylidine (at dose levels of 400--500 mg/kg/day) on the morphology and microsomal drug metabolising enzyme activity of the liver was studied in rats. All 3 isomers caused hepatomegaly which was considered to be due to proliferation of the smooth endoplasmic reticulum. Decreases in glycogen content and glucose-6-phosphatase activity were demonstrated histochemically. Biochemical investigations showed increases in microsomal protein and cytochrome P-450 content in rats dosed with 2,4- or 2,5-xylidine and in glucuronyltransferase activity in rats given 2,4-, 2,5- or 2,6-xylidine. Aniline hydroxylase activity was increased in all treated rats except males dosed with 2,6-xylidine. The results of the study indicate that all isomes of xylidine can be inducers of microsomal drug-metabolising enzyme activity, that they may be metabolised by oxidation and that the xylidine molecule may be eliminated as a conjugate with glucuronic acid.", "contents": "Hepatic effects of xylidine isomers in rats. The effect of repeated (4 weeks) oral administration of 2,4-, 2,5- or 2,6-xylidine (at dose levels of 400--500 mg/kg/day) on the morphology and microsomal drug metabolising enzyme activity of the liver was studied in rats. All 3 isomers caused hepatomegaly which was considered to be due to proliferation of the smooth endoplasmic reticulum. Decreases in glycogen content and glucose-6-phosphatase activity were demonstrated histochemically. Biochemical investigations showed increases in microsomal protein and cytochrome P-450 content in rats dosed with 2,4- or 2,5-xylidine and in glucuronyltransferase activity in rats given 2,4-, 2,5- or 2,6-xylidine. Aniline hydroxylase activity was increased in all treated rats except males dosed with 2,6-xylidine. The results of the study indicate that all isomes of xylidine can be inducers of microsomal drug-metabolising enzyme activity, that they may be metabolised by oxidation and that the xylidine molecule may be eliminated as a conjugate with glucuronic acid."}
{"id": "PMID:224541", "title": "[Pronase E and P immobilization on aminoorganosilica surface].", "content": "Immobilization of pronase E and P was performed on sylochrome modified by gamma-aminopropyltrietoxysilane using cyanuric chloride, 2,4--toluylenediisocyanate, glutaric aldehyde and also on sylochrome by means of titanium tetrachloride. The esterase and cas\u00e9inolytic activities of the immobilized preparations and their stability during storage were determined. The increased thermostability of the immobilized preparation is established. The influence of the enzyme: carrier ratio on the immobilization process and activity of the enzymes was studied. It is shown that application of glutaric aldehyde favours the best retention of the esterase activity (73%), whereas the caseinolytic activity is better retained (31%) when titanium tetrachloride was used.", "contents": "[Pronase E and P immobilization on aminoorganosilica surface]. Immobilization of pronase E and P was performed on sylochrome modified by gamma-aminopropyltrietoxysilane using cyanuric chloride, 2,4--toluylenediisocyanate, glutaric aldehyde and also on sylochrome by means of titanium tetrachloride. The esterase and cas\u00e9inolytic activities of the immobilized preparations and their stability during storage were determined. The increased thermostability of the immobilized preparation is established. The influence of the enzyme: carrier ratio on the immobilization process and activity of the enzymes was studied. It is shown that application of glutaric aldehyde favours the best retention of the esterase activity (73%), whereas the caseinolytic activity is better retained (31%) when titanium tetrachloride was used."}
{"id": "PMID:224542", "title": "[Immobilization of enzymic preparation of amylosubtilin G10x on silochrome].", "content": "The article deals with the process of immobilizing the enzymic preparation amylosubtilin G10x by the carriers activated with 2,4-toluylenediisocyanate and cyanurchloride which were obtained on the basis of silanized sylochrome. The 2,4-toluylenediisocyanate activated carrier is shown to be high-effective in immobilization. The activity of the preparations immobilized by the carrier activated with 2,4-toluylenediisocyatate is 75 units per 1 g of carrier; for the preparation immobilized on the carrier activated with cyanurchloride it is equal to 2.9 u/g. The specific activity is 3.1 and 0.9 u/mg, respectively. Immobilization on the tested carriers decreases the enzymic preparation thermostability.", "contents": "[Immobilization of enzymic preparation of amylosubtilin G10x on silochrome]. The article deals with the process of immobilizing the enzymic preparation amylosubtilin G10x by the carriers activated with 2,4-toluylenediisocyanate and cyanurchloride which were obtained on the basis of silanized sylochrome. The 2,4-toluylenediisocyanate activated carrier is shown to be high-effective in immobilization. The activity of the preparations immobilized by the carrier activated with 2,4-toluylenediisocyatate is 75 units per 1 g of carrier; for the preparation immobilized on the carrier activated with cyanurchloride it is equal to 2.9 u/g. The specific activity is 3.1 and 0.9 u/mg, respectively. Immobilization on the tested carriers decreases the enzymic preparation thermostability."}
{"id": "PMID:224546", "title": "The endocrine background of human renal cell carcinoma. I. Binding of the highly potent progestin R 5020 by tumour cytosol.", "content": "Based on the potential sensitivity of the growth of human renal cell carcinoma, tumour tissue from 88 patients was analysed for progestin receptors. With the dextran-coated charcoal assay, cytoplasmic components which bound the potent progestin R 5020 specifically and with high affinity could be detected in 42% of the carcinomas. The apparent dissociation constant of the R-5020-binder complex amounted to 3.1 +/- 1.2 X 10(-8) mol/l. Sedimentation in sucrose gradients revealed the bulk of these components to be in the 4-S region. The ligand specificity for binding to these sites indicated a requirement for progestins. Despite the enormous case material investigated, we were unable to confirm the presence of the high receptor concentrations reported in the literature.", "contents": "The endocrine background of human renal cell carcinoma. I. Binding of the highly potent progestin R 5020 by tumour cytosol. Based on the potential sensitivity of the growth of human renal cell carcinoma, tumour tissue from 88 patients was analysed for progestin receptors. With the dextran-coated charcoal assay, cytoplasmic components which bound the potent progestin R 5020 specifically and with high affinity could be detected in 42% of the carcinomas. The apparent dissociation constant of the R-5020-binder complex amounted to 3.1 +/- 1.2 X 10(-8) mol/l. Sedimentation in sucrose gradients revealed the bulk of these components to be in the 4-S region. The ligand specificity for binding to these sites indicated a requirement for progestins. Despite the enormous case material investigated, we were unable to confirm the presence of the high receptor concentrations reported in the literature."}
{"id": "PMID:224543", "title": "[Effect of physical load on cholesterol content in different classes of lipoproteins of blood serum and their decomposition].", "content": "An increase in the amount of cholesterol is established in blood serum high-density lipoproteins of rabbits which were subjected to moderate physical loads. Under these conditions an accelerated decay was also observed for lipoproteins of very low and low density.", "contents": "[Effect of physical load on cholesterol content in different classes of lipoproteins of blood serum and their decomposition]. An increase in the amount of cholesterol is established in blood serum high-density lipoproteins of rabbits which were subjected to moderate physical loads. Under these conditions an accelerated decay was also observed for lipoproteins of very low and low density."}
{"id": "PMID:224547", "title": "The endocrine background of human renal cell carcinoma. II. Attempt to induce the R-5020-binding components by oestrogens.", "content": "In an attempt to elevate the concentration of progestin-binding components in human renal cell carcinoma, 24 patients were treated prior to tumour nephrectomy with various doses of oestrogens, potent inducers of progestin receptor synthesis. Low-dose oestrogen treatment was found to be insufficient to significantly induce progestin-binder synthesis in the tumour tissue. In the carcinoma of patients receiving high-dose oestrogen treatment, the average concentration of R-5020-binding sites did not differ from that of the low-dose group. However, 2 out of these patients (12.5%) exhibited R-5020-binder concentrations in the tumour tissue which exceeded the highest quantities of progestin-binding components found in 88 untreated controls previously analysed in our laboratory.", "contents": "The endocrine background of human renal cell carcinoma. II. Attempt to induce the R-5020-binding components by oestrogens. In an attempt to elevate the concentration of progestin-binding components in human renal cell carcinoma, 24 patients were treated prior to tumour nephrectomy with various doses of oestrogens, potent inducers of progestin receptor synthesis. Low-dose oestrogen treatment was found to be insufficient to significantly induce progestin-binder synthesis in the tumour tissue. In the carcinoma of patients receiving high-dose oestrogen treatment, the average concentration of R-5020-binding sites did not differ from that of the low-dose group. However, 2 out of these patients (12.5%) exhibited R-5020-binder concentrations in the tumour tissue which exceeded the highest quantities of progestin-binding components found in 88 untreated controls previously analysed in our laboratory."}
{"id": "PMID:224548", "title": "Collagenase--a marker enzyme in human bladder cancer?", "content": "Collagenase activity in human bladder carcinomas was measured against 14C-labeled collagen as substrate. Enzymes activity in vivo increased with the degree of penetration of the bladder wall. It was not detectable or low in the cases of superficially infiltrating tumours (A, B1 B2) and high in the cases of deeply infiltrating tumours (C, D). These results suggest that collagenase activity of advanced tumours is predominantly expressed in the pervesical layer of the bladder wall. A quantitative estimate of this enzyme may thus help to distinguish between Stage C and Stage C tumour.", "contents": "Collagenase--a marker enzyme in human bladder cancer? Collagenase activity in human bladder carcinomas was measured against 14C-labeled collagen as substrate. Enzymes activity in vivo increased with the degree of penetration of the bladder wall. It was not detectable or low in the cases of superficially infiltrating tumours (A, B1 B2) and high in the cases of deeply infiltrating tumours (C, D). These results suggest that collagenase activity of advanced tumours is predominantly expressed in the pervesical layer of the bladder wall. A quantitative estimate of this enzyme may thus help to distinguish between Stage C and Stage C tumour."}
{"id": "PMID:224550", "title": "Somatostatin: selective inhibition of cyclic AMP stimulated protein kinase.", "content": "Utilizing histones as a substrate and measuring the production of labelled phosphoserine from [gamma 32P-ATP], cAMP stimulated protein kinase activity was found in islet and anterior pituitary secretory vesicles. Cyclic AMP (5 X 10(-7)m)stimulated islet secretory vesicle protein kinase activity as evidenced by a net  increase of 32P incorporation into phosphoserine 7.35 +/- 1.68 pmoles/micrograms, (P LESS THAN 9001). Somatostatin (0.1 ng/microgram) decreased 32P phosphoserine production from 10.64 +/- 1.72 to 5.61 +/- 1.26 pmoles/microgram (Pless than .01) by suppressing cAMP stimulated protein kinase activity. In pituitary secretory vesicles, cAMP (5 X 10(-6M) increased 32P incorporation into TCA precipitable protein from 127.3 +/- 8.6 to 202.6 +/- 12.5 pmoles/microgram, P less than .001. With somatostatin (0.2 ng/microgram) there was 55.25+/- 1.95% inhibition of cAMP stimulated protein kinase activity, (P LESS THAN .001). Somatostatin did not inhibit cAMP stimulated protein kinase activity in erythrocyte membrane ghosts nor did somatostatin inhibit the partially purified cAMP dependent protein kinase from cardiac muscle. These data suggest that either (1) a specific somatostatin sensitive dependent protein kinase is present in islet and anterior pituitary secretory vesicles or (2) that a somatostatin receptor is present in these tissues which allows somatostatin to act selectively at these sites. Somatostatin may act by inhibiting the cAMP dependent protein kinase enzme in certain key tissues or subcellular organelles.", "contents": "Somatostatin: selective inhibition of cyclic AMP stimulated protein kinase. Utilizing histones as a substrate and measuring the production of labelled phosphoserine from [gamma 32P-ATP], cAMP stimulated protein kinase activity was found in islet and anterior pituitary secretory vesicles. Cyclic AMP (5 X 10(-7)m)stimulated islet secretory vesicle protein kinase activity as evidenced by a net  increase of 32P incorporation into phosphoserine 7.35 +/- 1.68 pmoles/micrograms, (P LESS THAN 9001). Somatostatin (0.1 ng/microgram) decreased 32P phosphoserine production from 10.64 +/- 1.72 to 5.61 +/- 1.26 pmoles/microgram (Pless than .01) by suppressing cAMP stimulated protein kinase activity. In pituitary secretory vesicles, cAMP (5 X 10(-6M) increased 32P incorporation into TCA precipitable protein from 127.3 +/- 8.6 to 202.6 +/- 12.5 pmoles/microgram, P less than .001. With somatostatin (0.2 ng/microgram) there was 55.25+/- 1.95% inhibition of cAMP stimulated protein kinase activity, (P LESS THAN .001). Somatostatin did not inhibit cAMP stimulated protein kinase activity in erythrocyte membrane ghosts nor did somatostatin inhibit the partially purified cAMP dependent protein kinase from cardiac muscle. These data suggest that either (1) a specific somatostatin sensitive dependent protein kinase is present in islet and anterior pituitary secretory vesicles or (2) that a somatostatin receptor is present in these tissues which allows somatostatin to act selectively at these sites. Somatostatin may act by inhibiting the cAMP dependent protein kinase enzme in certain key tissues or subcellular organelles."}
{"id": "PMID:224554", "title": "Partial purification of thyroid hormone receptor from mitochondrial inner membrane: evidence for a physiologic role.", "content": "Recently we described a protein component, from the inner mitochondrial membrane, which binds thyroid hormone with high affinity, low capacity (saturable) characteristics. This partially purified rat liver mitochondrial membrane component appears to be a 150,000 daltons lipoprotein complex. Phospholipids, tentatively identified as lecithin, phosphatidyl ethanoamine, and cardiolipin, appear to constitute 50% of this complex. A similar hormone binding marcomolecule was also found in mitochondria from rabbit kidney, as well as human liver and kidney. In the rat this saturable thyroid hormone binding component was found in mitochondria from liver, kidney, myocardium, skeletal muscle, intestinal mucosa, whole small intestine, adipose tissue, and lung. It was absent from the mitochondria of adult brain, spleen and testis, organs known to be calorigenically unresponsive to thyroid hormones injected in vivo. In contrast, neonatal rat brains contain the protein with binding constants similar to those of neonatal or adult rat liver mitochondria, but in older rat brains (14 and 17 days) the saturable binding was no longer present, as in adult brain. These data provide strong support for the biological relevance of the mitochondrial component as a thyroid hormone receptor.", "contents": "Partial purification of thyroid hormone receptor from mitochondrial inner membrane: evidence for a physiologic role. Recently we described a protein component, from the inner mitochondrial membrane, which binds thyroid hormone with high affinity, low capacity (saturable) characteristics. This partially purified rat liver mitochondrial membrane component appears to be a 150,000 daltons lipoprotein complex. Phospholipids, tentatively identified as lecithin, phosphatidyl ethanoamine, and cardiolipin, appear to constitute 50% of this complex. A similar hormone binding marcomolecule was also found in mitochondria from rabbit kidney, as well as human liver and kidney. In the rat this saturable thyroid hormone binding component was found in mitochondria from liver, kidney, myocardium, skeletal muscle, intestinal mucosa, whole small intestine, adipose tissue, and lung. It was absent from the mitochondria of adult brain, spleen and testis, organs known to be calorigenically unresponsive to thyroid hormones injected in vivo. In contrast, neonatal rat brains contain the protein with binding constants similar to those of neonatal or adult rat liver mitochondria, but in older rat brains (14 and 17 days) the saturable binding was no longer present, as in adult brain. These data provide strong support for the biological relevance of the mitochondrial component as a thyroid hormone receptor."}
{"id": "PMID:224557", "title": "The earliest membrane responses to phagocytosis: membrane potential changes and Ca++ loss in human granulocytes.", "content": "The two findings reported here clearly indicate that the human granulocyte undergoes stimulus-secretion coupling when appropriate stimuli engage the cell surface. These secretory and metabolic responses seem designed to provide efficient mechanisms for bacterial killing or the elimination of immune complexes. First, ligands bind to surface receptors, in the case of concanavalin A, via surface sugars, in the case of immune complexes, via Fc receptors. Our new findings, described above, show that this is followed within five to ten seconds by membrane hyperpolarization: changes in the membrane potential of the cell: delta psi. Local loss of membrane calcium is noted concurrently: not as part of a generalized \"triggering\" of all the surface membraneof the cell, but only at the point of ligand-receptor interaction: the initiating point of phagocytosis. The subsequent changes, such as superoxide anion production, the generation of thromboxanes and prostaglandins, and the intracellular events which lead to secretion appear, therefore, to be secondary to these earliest membrane responses of phagocytosis.", "contents": "The earliest membrane responses to phagocytosis: membrane potential changes and Ca++ loss in human granulocytes. The two findings reported here clearly indicate that the human granulocyte undergoes stimulus-secretion coupling when appropriate stimuli engage the cell surface. These secretory and metabolic responses seem designed to provide efficient mechanisms for bacterial killing or the elimination of immune complexes. First, ligands bind to surface receptors, in the case of concanavalin A, via surface sugars, in the case of immune complexes, via Fc receptors. Our new findings, described above, show that this is followed within five to ten seconds by membrane hyperpolarization: changes in the membrane potential of the cell: delta psi. Local loss of membrane calcium is noted concurrently: not as part of a generalized \"triggering\" of all the surface membraneof the cell, but only at the point of ligand-receptor interaction: the initiating point of phagocytosis. The subsequent changes, such as superoxide anion production, the generation of thromboxanes and prostaglandins, and the intracellular events which lead to secretion appear, therefore, to be secondary to these earliest membrane responses of phagocytosis."}
{"id": "PMID:224563", "title": "Comparison of two infectious bursal disease vaccine strains: efficacy and potential hazards in susceptible and maternally immune birds.", "content": "Two infectious bursal disease vaccines were administered to separate groups of maternally immune and susceptible chickens at various ages. Vaccine B caused no damage to the bursae of chickens examined histologically at nine and 20 days after vaccination. The bursae of chickens given vaccine A were shown to be severely damaged when similarly examined. Both vaccines protected all the susceptible groups against challenge, but only vaccine A protected the groups of maternally immune chickens. Susceptible chickens vaccinated at one day of age with vaccine A showed a lowered response to Hitchner B1 Newcastle disease vaccine given at 14 days of age, judged by the haemagglutination-inhibition response and Newcastle disease challenge. The performance of the Newcastle disease vaccine was not affected in chickens given vaccine B. Bedding used by birds given vaccine A was shown to be capable of transmitting vaccinal virus to susceptible chickens, causing severe bursal damage.", "contents": "Comparison of two infectious bursal disease vaccine strains: efficacy and potential hazards in susceptible and maternally immune birds. Two infectious bursal disease vaccines were administered to separate groups of maternally immune and susceptible chickens at various ages. Vaccine B caused no damage to the bursae of chickens examined histologically at nine and 20 days after vaccination. The bursae of chickens given vaccine A were shown to be severely damaged when similarly examined. Both vaccines protected all the susceptible groups against challenge, but only vaccine A protected the groups of maternally immune chickens. Susceptible chickens vaccinated at one day of age with vaccine A showed a lowered response to Hitchner B1 Newcastle disease vaccine given at 14 days of age, judged by the haemagglutination-inhibition response and Newcastle disease challenge. The performance of the Newcastle disease vaccine was not affected in chickens given vaccine B. Bedding used by birds given vaccine A was shown to be capable of transmitting vaccinal virus to susceptible chickens, causing severe bursal damage."}
{"id": "PMID:224567", "title": "Double tumours of the liver following intravenous thorotrast injection. Patho-anatomical report on two cases.", "content": "Observations on the contrast between the livers of two patients who underwent an arteriogram with thorotrast in 1941 have been made. The first case produced a cholangicellular carcinoma (CCC) in addition to atypical proliferations of sinusoidal lining cells. The second case produced a very rare tumour combination of a CCC with a haemangioendothelial sarcoma (Haem-SA the problem of double tumours of the liver following thorotrast injection is discussed in the light of these cases. In addition the discussion includes various opinions on Kupffer cells.", "contents": "Double tumours of the liver following intravenous thorotrast injection. Patho-anatomical report on two cases. Observations on the contrast between the livers of two patients who underwent an arteriogram with thorotrast in 1941 have been made. The first case produced a cholangicellular carcinoma (CCC) in addition to atypical proliferations of sinusoidal lining cells. The second case produced a very rare tumour combination of a CCC with a haemangioendothelial sarcoma (Haem-SA the problem of double tumours of the liver following thorotrast injection is discussed in the light of these cases. In addition the discussion includes various opinions on Kupffer cells."}
{"id": "PMID:224568", "title": "Bronchial mucous gland tumours.", "content": "Tumours arising in the bronchial mucous glands closely resemble tumours arising in the mixed salivary glands. Bronchial mucous gland tumours account for less than 0.5 per cent of all lung tumours. Twenty six tumours are reviewed and they have been divided into five types, (a) adenoidcystic carcinomas, (b) muco-epidermoid tumors, (c) mixed (pleomorphic) tumors, (d) cystadenomas and (f) oxyphilic adenoma. The clinical features, and postoperative course of the patients are reviewed. Adenocystic carcinomas, arising in the bronchus frequently involve the neighbouring trachea and spread mainly by direct infiltration. Most muco-epidermoid bronchial tumours were confined to young persons, and the only malignant muco-epidermoid tumour occurred in an elderly person. The prognosis in young persons is good provided the tumours are completely excised. The two mixed bronchial tumours resembled their salivary counterparts and one subsequently behaved as a carcinoma and metastasised. Bronchial cystadenomas all proved to be benign tumours but in two cases were associated with surface papillary proliferation. The only example of an oxyphil cell adenoma was discovered at post mortem examination. The histogenesis of the tumours is considered.", "contents": "Bronchial mucous gland tumours. Tumours arising in the bronchial mucous glands closely resemble tumours arising in the mixed salivary glands. Bronchial mucous gland tumours account for less than 0.5 per cent of all lung tumours. Twenty six tumours are reviewed and they have been divided into five types, (a) adenoidcystic carcinomas, (b) muco-epidermoid tumors, (c) mixed (pleomorphic) tumors, (d) cystadenomas and (f) oxyphilic adenoma. The clinical features, and postoperative course of the patients are reviewed. Adenocystic carcinomas, arising in the bronchus frequently involve the neighbouring trachea and spread mainly by direct infiltration. Most muco-epidermoid bronchial tumours were confined to young persons, and the only malignant muco-epidermoid tumour occurred in an elderly person. The prognosis in young persons is good provided the tumours are completely excised. The two mixed bronchial tumours resembled their salivary counterparts and one subsequently behaved as a carcinoma and metastasised. Bronchial cystadenomas all proved to be benign tumours but in two cases were associated with surface papillary proliferation. The only example of an oxyphil cell adenoma was discovered at post mortem examination. The histogenesis of the tumours is considered."}
{"id": "PMID:224569", "title": "Fibrous histiocytoma: an analysis of the storiform pattern.", "content": "A storiform pattern is an important structural feature of fibrous histiocytoma (FH). In this analysis reconstructions of histological patterns were carried out from drawings. Highly FH with only a suggestion of storiform pattern and small star-formations were seen, there were other lesions with more pronounced fiber formation which showed more distinct and larger storiform stars. These structures can frequently be followed for only 3 sections of 5 micron thickness. In contrast to leiomyomas or meningioma, no regular or consistent orientation of these structures with respect to vessels is evident. Storiform structures apparently develop at the periphery of adjacent proliferating cells groups. They show a typical and diagnostically significant histological pattern, which was found to some degree in all FH examined.", "contents": "Fibrous histiocytoma: an analysis of the storiform pattern. A storiform pattern is an important structural feature of fibrous histiocytoma (FH). In this analysis reconstructions of histological patterns were carried out from drawings. Highly FH with only a suggestion of storiform pattern and small star-formations were seen, there were other lesions with more pronounced fiber formation which showed more distinct and larger storiform stars. These structures can frequently be followed for only 3 sections of 5 micron thickness. In contrast to leiomyomas or meningioma, no regular or consistent orientation of these structures with respect to vessels is evident. Storiform structures apparently develop at the periphery of adjacent proliferating cells groups. They show a typical and diagnostically significant histological pattern, which was found to some degree in all FH examined."}
{"id": "PMID:224570", "title": "Nonchromaffin paraganglioma of the duodenum.", "content": "A benign nonchromaffin paraganglioma of the duodenum is described and compared with other reported cases. Duodenal location is extremely rare but the morphology, based on the optical microscopic pattern (Zellballen) and the ultrastructural appearance is, comparable with paragangliomas of other sites. The lack of nerve fibres and ganglion cells in this tumour, together with the absence of a positive chromaffin reaction permits us to classify it as a pure nonchromaffin paraganglioma. This finding constitutes indirect evidence of the probable existence of a paraganglion in the duodenal wall, a structure not yet demonstrated in the adult.", "contents": "Nonchromaffin paraganglioma of the duodenum. A benign nonchromaffin paraganglioma of the duodenum is described and compared with other reported cases. Duodenal location is extremely rare but the morphology, based on the optical microscopic pattern (Zellballen) and the ultrastructural appearance is, comparable with paragangliomas of other sites. The lack of nerve fibres and ganglion cells in this tumour, together with the absence of a positive chromaffin reaction permits us to classify it as a pure nonchromaffin paraganglioma. This finding constitutes indirect evidence of the probable existence of a paraganglion in the duodenal wall, a structure not yet demonstrated in the adult."}
{"id": "PMID:224597", "title": "[cAMP phosphodiesterase activity in the leukocytes in bronchial asthma].", "content": "Activity of cAMP phosphodiesterase was similar in leukocytes of healthy persons and of the patients with bronchial asthma in the period of remission. The enzymatic activity was independent on the form of the impairment (infectious-allergic or atopic types). Sensivity of cAMP phosphodiesterase to the effect of its inhibitors and stimulants--theophylline, papaverine and imidazole was higher in the patients as compared with the healthy persons. Prolonged therapy with the phosphodiesterase inhibitors did not lead to development of resistance.", "contents": "[cAMP phosphodiesterase activity in the leukocytes in bronchial asthma]. Activity of cAMP phosphodiesterase was similar in leukocytes of healthy persons and of the patients with bronchial asthma in the period of remission. The enzymatic activity was independent on the form of the impairment (infectious-allergic or atopic types). Sensivity of cAMP phosphodiesterase to the effect of its inhibitors and stimulants--theophylline, papaverine and imidazole was higher in the patients as compared with the healthy persons. Prolonged therapy with the phosphodiesterase inhibitors did not lead to development of resistance."}
{"id": "PMID:224603", "title": "[Does the concept for the prevention of chronic ischemic heart disease correspond to current ideas on etiology and pathogenesis of arteriosclerosis?].", "content": "A summarizing description of the essential relations between the existence of risk factors and the course of the morphologic changes in the arteriosclerosis in the intima is given. In this process the low density lipoproteins play an important role which together with further etiologic factors contribute to an increased permeability of the endothelium and to the stimulation of the proliferation and modulation of the smooth muscle cells, which are of central importance in the vascular reaction. Certain effects on the progression of the arteriosclerosis as well as a regression of adequate morphologic changes are to be expected from an elimination of risk factors, provided the necessary measures begin in the early stages of the arteriosclerosis, i. e. in the preatheromatous stage.", "contents": "[Does the concept for the prevention of chronic ischemic heart disease correspond to current ideas on etiology and pathogenesis of arteriosclerosis?]. A summarizing description of the essential relations between the existence of risk factors and the course of the morphologic changes in the arteriosclerosis in the intima is given. In this process the low density lipoproteins play an important role which together with further etiologic factors contribute to an increased permeability of the endothelium and to the stimulation of the proliferation and modulation of the smooth muscle cells, which are of central importance in the vascular reaction. Certain effects on the progression of the arteriosclerosis as well as a regression of adequate morphologic changes are to be expected from an elimination of risk factors, provided the necessary measures begin in the early stages of the arteriosclerosis, i. e. in the preatheromatous stage."}
{"id": "PMID:224604", "title": "[Benign and semimalignant intrabronchial lung tumors].", "content": "From 1961 to 1977 we observed 14 patients with semimalignant and benign intrabronchial tumours. In our own patients only a proportion of 0.8% of all bronchial tumours was of non-malignant or semimalignant origin. It is referred to the symptomatology, diagnostics and therapy of these tumours (7 carcinoids, 1 malignant degenerated carcinoid, 1 metastasizing cylindrome, 2 adenomas, 1 intrabronchial chondroma, 2 neurofibromas). The authors especially deal with the possibility of an endobronchial removal of tumours.", "contents": "[Benign and semimalignant intrabronchial lung tumors]. From 1961 to 1977 we observed 14 patients with semimalignant and benign intrabronchial tumours. In our own patients only a proportion of 0.8% of all bronchial tumours was of non-malignant or semimalignant origin. It is referred to the symptomatology, diagnostics and therapy of these tumours (7 carcinoids, 1 malignant degenerated carcinoid, 1 metastasizing cylindrome, 2 adenomas, 1 intrabronchial chondroma, 2 neurofibromas). The authors especially deal with the possibility of an endobronchial removal of tumours."}
{"id": "PMID:224598", "title": "[Distribution of the reducing equivalents in the cell in the active phase of benz(a)pyrene metabolism].", "content": "Hydroxylation of benz/a/pyrene might occur under decreased activity of NADPH-dependent reductase. In vivo a decrease in the activity of NADPH-dependent reductase did not influence apparently the intensity of benz/a/pyrene hydroxylation, which is maintained due to redistribution of reducing equivalents between oxygenase and oxidase systems in the cells. Anticarcinogenic effects of two different substances chrisene and ubiquinone are discussed taking into account possible normalization of NADPH- and NADH-dependent oxidative reactions in the cells.", "contents": "[Distribution of the reducing equivalents in the cell in the active phase of benz(a)pyrene metabolism]. Hydroxylation of benz/a/pyrene might occur under decreased activity of NADPH-dependent reductase. In vivo a decrease in the activity of NADPH-dependent reductase did not influence apparently the intensity of benz/a/pyrene hydroxylation, which is maintained due to redistribution of reducing equivalents between oxygenase and oxidase systems in the cells. Anticarcinogenic effects of two different substances chrisene and ubiquinone are discussed taking into account possible normalization of NADPH- and NADH-dependent oxidative reactions in the cells."}
{"id": "PMID:224600", "title": "[Activity of the key glycolysis and respiration enzymes in the rat liver in chemical carcinogenesis].", "content": "Activities of hexokinase, glucokinase, cytochrome oxidase as well as amount of mitochondrial protein and subcellular distribution of hexokinase were studied in rat liver tissue after administration of acetyl aminofluorene and diethyl nitrosamine. Activity of the enzymes was altered in the same direction both in the primary induced hepatomas and in transplantable tumors of liver tissue. Glucokinase was not found but the fraction of hexokinase bound to mitochondrial membranes was observed in all the primary hepatomas studied; in this property the tumors resembled the embryonal liver tissue, various tissues of mature animals and transplantable hepatomas. This pattern of distribution of the enzymes reflects biochemical and functional disdifferentiation of the hepatomas. Properties of the bound hexokinase from the hepatoma were similar to those of the enzyme from embryonal liver tissue and, hence, they were distinct as compared with the enzymatic properties of hexokinase in the transplantable hepatomas.", "contents": "[Activity of the key glycolysis and respiration enzymes in the rat liver in chemical carcinogenesis]. Activities of hexokinase, glucokinase, cytochrome oxidase as well as amount of mitochondrial protein and subcellular distribution of hexokinase were studied in rat liver tissue after administration of acetyl aminofluorene and diethyl nitrosamine. Activity of the enzymes was altered in the same direction both in the primary induced hepatomas and in transplantable tumors of liver tissue. Glucokinase was not found but the fraction of hexokinase bound to mitochondrial membranes was observed in all the primary hepatomas studied; in this property the tumors resembled the embryonal liver tissue, various tissues of mature animals and transplantable hepatomas. This pattern of distribution of the enzymes reflects biochemical and functional disdifferentiation of the hepatomas. Properties of the bound hexokinase from the hepatoma were similar to those of the enzyme from embryonal liver tissue and, hence, they were distinct as compared with the enzymatic properties of hexokinase in the transplantable hepatomas."}
{"id": "PMID:224605", "title": "[Demonstration of hepatitis A virus in the feces].", "content": "On the basis of own examinations methodology and results of the demonstration of the virus A in the stools and of the proof of antibodies in the serum are described. The parameters of the virus-A-hepatitis which are important for practice are further the basis for diagnosis, therapy and surrounding prophylaxis in routine work. They were compiled in a table.", "contents": "[Demonstration of hepatitis A virus in the feces]. On the basis of own examinations methodology and results of the demonstration of the virus A in the stools and of the proof of antibodies in the serum are described. The parameters of the virus-A-hepatitis which are important for practice are further the basis for diagnosis, therapy and surrounding prophylaxis in routine work. They were compiled in a table."}
{"id": "PMID:224599", "title": "[Plasma lipoproteins and aortic collagen fractions in rabbits with different degrees of atherosclerosis].", "content": "Content of cholesterol and of collagen fractions (salt-, acid soluble and insoluble) in thoracal and peritoneal parts of aorta as well as concentration of products of collagen metabolism (protein-bound and free hydroxyproline) in blood plasma were studied in rabbits with various degree of atherosclerosis--separate lipid spots in aorta thoracal part (I group), total impairment of aorta (II group) and in control animals. Concentration of cholesterol and triglycerides was also studied in blood plasma and content of cholesterol, cholesterol and triglyceride esters, phospholipids and protein was measured in separate types of lipoproteins--lipoprotein of low (LPLD), of very low (LPVLD) and of high density (LPHD). Increase in content of cholesterol, salt-soluble and insoluble collagen from the both parts of aorta as well as in concentration of protein-bound and free hydroxyproline was found in rabbits of the II group as compared with the control animals. In animals of the I group content of collagen fractions in aorta was similar to that of control animals. Hypercholesterolemia, observed in both groups of rabbits, was most distinct in the II group, being related to the higher amount of cholesterol in LPLD fraction. The ratio of cholesterol esters, free cholesterol, triglycerides and phospholipids was similarly altered in LPVLD fraction of the groups of animals, mainly due to an increase in content of cholesterol esters. But rabbits of the I group were distinct from the II group of animals in the ratio of these components in LPLD: relative content of protein was lower and of cholesterol esters--higher in LPLD of the II group than of the I group. The data suggest that LPLD contained high amount of lipoproteins of intermediate density and cholesterol deposited into vessel wall from LPLD and lipoproteins of intermediate density at the increased rate. In LPHD from blood plasma of rabbits of the II group the ratios cholesterol/protein, cholesterol esters/protein as well as the molar ratio free cholesterol/phospholipids were increased; these data suggest that LPHD was saturated with cholesterol and LPHD appeared to lose the ability to eliminate cholesterol from the vessel wall. Differences in the degree of atherosclerotic impairments, existing between the I and II groups of animals, were apparently related to the variations in composition and content of lipoproteins, which regulate the level of cholesterol in vessel wall, as well as to content of collagen, i. e. they were due to features of metabolism of lipoproteins in blood plasma and of collagen in the vascular wall.", "contents": "[Plasma lipoproteins and aortic collagen fractions in rabbits with different degrees of atherosclerosis]. Content of cholesterol and of collagen fractions (salt-, acid soluble and insoluble) in thoracal and peritoneal parts of aorta as well as concentration of products of collagen metabolism (protein-bound and free hydroxyproline) in blood plasma were studied in rabbits with various degree of atherosclerosis--separate lipid spots in aorta thoracal part (I group), total impairment of aorta (II group) and in control animals. Concentration of cholesterol and triglycerides was also studied in blood plasma and content of cholesterol, cholesterol and triglyceride esters, phospholipids and protein was measured in separate types of lipoproteins--lipoprotein of low (LPLD), of very low (LPVLD) and of high density (LPHD). Increase in content of cholesterol, salt-soluble and insoluble collagen from the both parts of aorta as well as in concentration of protein-bound and free hydroxyproline was found in rabbits of the II group as compared with the control animals. In animals of the I group content of collagen fractions in aorta was similar to that of control animals. Hypercholesterolemia, observed in both groups of rabbits, was most distinct in the II group, being related to the higher amount of cholesterol in LPLD fraction. The ratio of cholesterol esters, free cholesterol, triglycerides and phospholipids was similarly altered in LPVLD fraction of the groups of animals, mainly due to an increase in content of cholesterol esters. But rabbits of the I group were distinct from the II group of animals in the ratio of these components in LPLD: relative content of protein was lower and of cholesterol esters--higher in LPLD of the II group than of the I group. The data suggest that LPLD contained high amount of lipoproteins of intermediate density and cholesterol deposited into vessel wall from LPLD and lipoproteins of intermediate density at the increased rate. In LPHD from blood plasma of rabbits of the II group the ratios cholesterol/protein, cholesterol esters/protein as well as the molar ratio free cholesterol/phospholipids were increased; these data suggest that LPHD was saturated with cholesterol and LPHD appeared to lose the ability to eliminate cholesterol from the vessel wall. Differences in the degree of atherosclerotic impairments, existing between the I and II groups of animals, were apparently related to the variations in composition and content of lipoproteins, which regulate the level of cholesterol in vessel wall, as well as to content of collagen, i. e. they were due to features of metabolism of lipoproteins in blood plasma and of collagen in the vascular wall."}
{"id": "PMID:224606", "title": "Plasma-estrogens and liver cirrhosis.", "content": "The plasma concentrations of estrogens as well as their relationship to testosterone are determined in male patients suffering from fatty liver, chronic hepatitis and cirrhosis of the liver. By stimulation and suppresion tests the contribution of the adrenal gland and the testes to the elevated estrogens are investigated, demonstrating that enhanced peripheral conversion of androgens to estrone rather than to estradiol appears to be more effective in sustaining plasma levels in hepatic cirrhosis. Futhermore, the effect of testosterone application was studied in male patients with alcohol-induced cirrhosis of the liver in order to realize possible side-effects of an androgenic substitution therapy. It is concluded that clinical signs of hyper-estrogensim and hypoandrogenism in male patients with hepatic cirrhosis may in part be attributed to the increase of estrogens and the decrease of total and free testosterone, as is best shown by the ration of the heterosexual hormones which are grossly shifted in favour of the estrogens.", "contents": "Plasma-estrogens and liver cirrhosis. The plasma concentrations of estrogens as well as their relationship to testosterone are determined in male patients suffering from fatty liver, chronic hepatitis and cirrhosis of the liver. By stimulation and suppresion tests the contribution of the adrenal gland and the testes to the elevated estrogens are investigated, demonstrating that enhanced peripheral conversion of androgens to estrone rather than to estradiol appears to be more effective in sustaining plasma levels in hepatic cirrhosis. Futhermore, the effect of testosterone application was studied in male patients with alcohol-induced cirrhosis of the liver in order to realize possible side-effects of an androgenic substitution therapy. It is concluded that clinical signs of hyper-estrogensim and hypoandrogenism in male patients with hepatic cirrhosis may in part be attributed to the increase of estrogens and the decrease of total and free testosterone, as is best shown by the ration of the heterosexual hormones which are grossly shifted in favour of the estrogens."}
{"id": "PMID:224607", "title": "Glucocorticoid and mineralocorticoid hormones in chronic liver diseases.", "content": "In patients with chronic liver disease a dissociation of the two most important partial functions of the adrenal cortex may be observed. A widening of the zona glomerulosa is associated with an increased aldosterone secretion and an atrophy of the zona fasciculata with a decreased cortisol production rate. In acute alcoholic liver damage there are sometimes remarkable special features concerning the adrenal function. The pathogenesis of the altered C21-steroid hormone metabolism is nonuniform and depends upon the etiology of the liver disease. Following factors may play role: 1. Decreased activity of specific hepatic enzymes a)direct enzyme damage b)indirect enzyme activity decreasing processed by deficiency of hydrogen from NADPH 2. Decreased hepatic blood flow 3. Disturbance of intracellular transport of substrates (e.g. cholestasis 4. Changes of transport proteins. 5. Direct or reactive changes of other factors of hormonal feedback systems (hypothalamus-pituitary-adrenal or gonadal-system; renin-angiotensin-aldosterone-system).", "contents": "Glucocorticoid and mineralocorticoid hormones in chronic liver diseases. In patients with chronic liver disease a dissociation of the two most important partial functions of the adrenal cortex may be observed. A widening of the zona glomerulosa is associated with an increased aldosterone secretion and an atrophy of the zona fasciculata with a decreased cortisol production rate. In acute alcoholic liver damage there are sometimes remarkable special features concerning the adrenal function. The pathogenesis of the altered C21-steroid hormone metabolism is nonuniform and depends upon the etiology of the liver disease. Following factors may play role: 1. Decreased activity of specific hepatic enzymes a)direct enzyme damage b)indirect enzyme activity decreasing processed by deficiency of hydrogen from NADPH 2. Decreased hepatic blood flow 3. Disturbance of intracellular transport of substrates (e.g. cholestasis 4. Changes of transport proteins. 5. Direct or reactive changes of other factors of hormonal feedback systems (hypothalamus-pituitary-adrenal or gonadal-system; renin-angiotensin-aldosterone-system)."}
{"id": "PMID:224608", "title": "Fine structure and histochemistry of the gastric shield in the lamellibranch Donax trunculus L.", "content": "The histochemical observations performed by the authors on the stomach wall of Donax trunculus are not wholly in agreement with the results of workers on other bivalves. The ultrastructure of the gastric shield and underlying cells was therefore, studied. It was confirmed that the epithelial cells contain glycogen granules at the base. In addition two distanct P.A.S. positive inclusions were identified: lysosomal residual bodies and neutral mucopolysaccharidic inclusions. The gastric shield is composed largely of long narrow microvilli embedded in a chitinous glycocalyx but is nevertheless easily removable. Hence, there is no causal relationship between abundance of microvilli and the possibility of removing the shield.", "contents": "Fine structure and histochemistry of the gastric shield in the lamellibranch Donax trunculus L. The histochemical observations performed by the authors on the stomach wall of Donax trunculus are not wholly in agreement with the results of workers on other bivalves. The ultrastructure of the gastric shield and underlying cells was therefore, studied. It was confirmed that the epithelial cells contain glycogen granules at the base. In addition two distanct P.A.S. positive inclusions were identified: lysosomal residual bodies and neutral mucopolysaccharidic inclusions. The gastric shield is composed largely of long narrow microvilli embedded in a chitinous glycocalyx but is nevertheless easily removable. Hence, there is no causal relationship between abundance of microvilli and the possibility of removing the shield."}
{"id": "PMID:224613", "title": "[Sujective evaluation of the duration of sleep periods: role of actual time and the representation rate of different EEG stages].", "content": "Subjective estimations of the duration of night sleep periods and their actual duration were compared in 29 healthy men 21--36 years of age, awoken from the night sleep. The comparisons concerned the duration of consecutive sleep cycles, long (almost whole sleep cycles) and short (\"parts of the cycles\") periods, short periods (\"parts of the cycle\") without REM and with it. It has been found that long and short sleep periods are correspondingly reflected in the subjective estimation of their duration. The comparison of the estimation rates of various stages revealed that the highest subjective estimation, reduced to an hour of real time (subjective \"hour estimation\") in the first three sleep cycles characterises the cycle parts, including REM, whereas the lowest one--cycle parts, represented only by slow sleep stages, including delta-sleep. Subjective estimation of the sleep cycle duration regularly lowers throughout night sleep from evening till morning. Thus, subjective estimation of the duration of sleep periods is determined by two factors: their actual duration and manifestation rate of different sleep stages. The course of subjective time count in the sleep cycle seems to be uneven: it is slowed down in delta-sleep and accelerated in REM sleep following delta-sleep.", "contents": "[Sujective evaluation of the duration of sleep periods: role of actual time and the representation rate of different EEG stages]. Subjective estimations of the duration of night sleep periods and their actual duration were compared in 29 healthy men 21--36 years of age, awoken from the night sleep. The comparisons concerned the duration of consecutive sleep cycles, long (almost whole sleep cycles) and short (\"parts of the cycles\") periods, short periods (\"parts of the cycle\") without REM and with it. It has been found that long and short sleep periods are correspondingly reflected in the subjective estimation of their duration. The comparison of the estimation rates of various stages revealed that the highest subjective estimation, reduced to an hour of real time (subjective \"hour estimation\") in the first three sleep cycles characterises the cycle parts, including REM, whereas the lowest one--cycle parts, represented only by slow sleep stages, including delta-sleep. Subjective estimation of the sleep cycle duration regularly lowers throughout night sleep from evening till morning. Thus, subjective estimation of the duration of sleep periods is determined by two factors: their actual duration and manifestation rate of different sleep stages. The course of subjective time count in the sleep cycle seems to be uneven: it is slowed down in delta-sleep and accelerated in REM sleep following delta-sleep."}
{"id": "PMID:224615", "title": "[Effect of emotional stress on sleep dynamics in cats].", "content": "Emotional stress was developed in cats by putting them in one cage with dogs for 24 hours. Then the 24 hours sleep-walking cycles records revealed prolonged REM stage in day time or at night in five animals out of seven, and in six animals a general increase of REM sleep duration over 24 hours. Simultaneously, in six animals the length of drowsiness and of deep slow-wave sleep stages was reduced. Increased overall sleep duration in the 24 hours was recorded in five cats. Sleep changes dynamics analysis reveals three stages: 1) sharp shift of all sleep parameters--27%, 2) deviation in sleep parameters--34% and 3) returning to basic sleep parameters--in 38%. The conclusion is drawn that sleep disorders may be used as an index of higher nervous activity disturbance in waking state.", "contents": "[Effect of emotional stress on sleep dynamics in cats]. Emotional stress was developed in cats by putting them in one cage with dogs for 24 hours. Then the 24 hours sleep-walking cycles records revealed prolonged REM stage in day time or at night in five animals out of seven, and in six animals a general increase of REM sleep duration over 24 hours. Simultaneously, in six animals the length of drowsiness and of deep slow-wave sleep stages was reduced. Increased overall sleep duration in the 24 hours was recorded in five cats. Sleep changes dynamics analysis reveals three stages: 1) sharp shift of all sleep parameters--27%, 2) deviation in sleep parameters--34% and 3) returning to basic sleep parameters--in 38%. The conclusion is drawn that sleep disorders may be used as an index of higher nervous activity disturbance in waking state."}
{"id": "PMID:224617", "title": "Prostaglandin E2 and F2 alpha levels in human dental cyst fluid as bone resorbing factors?", "content": "Prostaglandin E2 and F2 alpha concentrations in aspirated cyst fluid of 14 human dental cysts were measured by radioimmunoassay. The mean concentrations were found to be 22.0 ng PGE2/g cyst fluid and 4.0 ng PGF2 alpha/g cyst fluid. As compared to plasma conditions a remarkable shift of the ratio of the two prostaglandins to PGE2 could be demonstrated. Due to the high concentrations of PGE2 found in the cyst material it is suggested that this prostaglandin may be one of the bone resorbing factors to be responsible for the destruction of bone in periodontal diseases.", "contents": "Prostaglandin E2 and F2 alpha levels in human dental cyst fluid as bone resorbing factors? Prostaglandin E2 and F2 alpha concentrations in aspirated cyst fluid of 14 human dental cysts were measured by radioimmunoassay. The mean concentrations were found to be 22.0 ng PGE2/g cyst fluid and 4.0 ng PGF2 alpha/g cyst fluid. As compared to plasma conditions a remarkable shift of the ratio of the two prostaglandins to PGE2 could be demonstrated. Due to the high concentrations of PGE2 found in the cyst material it is suggested that this prostaglandin may be one of the bone resorbing factors to be responsible for the destruction of bone in periodontal diseases."}
{"id": "PMID:224622", "title": "Phosphatase production by microorganisms isolated from diverse types of soils.", "content": "Qualitative and quantitative nature of phosphatases produced by various fungal, bacterial, and actinomycetes isolates from diverse soils was examined. Soil fungi, particularly those belonging to the genera Aspergillus and Penicillium, were found to be most effective in producing phosphatases intra- and extracellularly. None of the 16 bacterial isolates produced acid phosphatase, but most of them did produce neutral phosphatase. Actinomycetes produced only negligible quantities of phosphatases.", "contents": "Phosphatase production by microorganisms isolated from diverse types of soils. Qualitative and quantitative nature of phosphatases produced by various fungal, bacterial, and actinomycetes isolates from diverse soils was examined. Soil fungi, particularly those belonging to the genera Aspergillus and Penicillium, were found to be most effective in producing phosphatases intra- and extracellularly. None of the 16 bacterial isolates produced acid phosphatase, but most of them did produce neutral phosphatase. Actinomycetes produced only negligible quantities of phosphatases."}
{"id": "PMID:224618", "title": "[Pathobiochemistry of organ fibroses. Changes in the connective tissue metabolism in liver fibrosis and in chronic polyarthritis].", "content": "Many chronic inflammations of various origin are characterized by an elevated metabolic activity of connective tissue, causing an increased tissue proliferation. The authors first review the more recent methods of analyzing the connective tissue metabolism. Details of changes of this metabolism are described with reference to liver fibrosis and rheumatoid arthritis. First steps of a pathobiochemical diagnosis of activity in organ fibroses are discussed. It seems possible to judge the activity of liver fibrosis by estimating the serum activity of lysosomal glycosidases and serum levels of terminal collagen peptides. Elevated antiprotease serum levels in rheumatoid patients may indicate an inflammatory activity.", "contents": "[Pathobiochemistry of organ fibroses. Changes in the connective tissue metabolism in liver fibrosis and in chronic polyarthritis]. Many chronic inflammations of various origin are characterized by an elevated metabolic activity of connective tissue, causing an increased tissue proliferation. The authors first review the more recent methods of analyzing the connective tissue metabolism. Details of changes of this metabolism are described with reference to liver fibrosis and rheumatoid arthritis. First steps of a pathobiochemical diagnosis of activity in organ fibroses are discussed. It seems possible to judge the activity of liver fibrosis by estimating the serum activity of lysosomal glycosidases and serum levels of terminal collagen peptides. Elevated antiprotease serum levels in rheumatoid patients may indicate an inflammatory activity."}
{"id": "PMID:224619", "title": "[The effect of pathogenic factors and anti-rheumatic drugs on the proliferation of cultured human fibroblasts].", "content": "1. Staphylolysin and low density lipoprotein (LDL) stimulate the proliferation of cultivated fetal human fibroblasts of the lung. 2. Antirheumatic drugs (prednisolone, acetylsalicylic acid, D-penicillamine and chloroquine) inhibit the proliferation of cultivated fetal human fibroblasts. 3. Antirheumatic drugs (prednisolone, acetylsalicylic acid, D-penicillamine and chloroquine), simultaneously added to the cluture eliminate the acceleration of the proliferation induced by staphylolysine or low density lipoprotein. 4. These results suggest, that in rheumatic diseases either pathogenic factors or antirheumatic drugs stimulate or inhibit, respectively, directly the cells of the connective tissue. Arterial wall cells, being mesenchymal cells, react in similar way on staphylolysine, low density lipoprotein and antirheumatic drugs. The similarity between the rheumatic and the arteriosclerotic process suggest to use antirheumatic drugs in the prevention and therapy of human arteriosclerosis.", "contents": "[The effect of pathogenic factors and anti-rheumatic drugs on the proliferation of cultured human fibroblasts]. 1. Staphylolysin and low density lipoprotein (LDL) stimulate the proliferation of cultivated fetal human fibroblasts of the lung. 2. Antirheumatic drugs (prednisolone, acetylsalicylic acid, D-penicillamine and chloroquine) inhibit the proliferation of cultivated fetal human fibroblasts. 3. Antirheumatic drugs (prednisolone, acetylsalicylic acid, D-penicillamine and chloroquine), simultaneously added to the cluture eliminate the acceleration of the proliferation induced by staphylolysine or low density lipoprotein. 4. These results suggest, that in rheumatic diseases either pathogenic factors or antirheumatic drugs stimulate or inhibit, respectively, directly the cells of the connective tissue. Arterial wall cells, being mesenchymal cells, react in similar way on staphylolysine, low density lipoprotein and antirheumatic drugs. The similarity between the rheumatic and the arteriosclerotic process suggest to use antirheumatic drugs in the prevention and therapy of human arteriosclerosis."}
{"id": "PMID:224627", "title": "[Experience in examining infectious hepatitis patients by using a viral detection method].", "content": "Immune electron microscopy was shown to be an acceptable diagnostic method which allowed to detect hepatitis A virus particles in the stools of patients with infectious hepatitis even at the late stages of the disease. The examination of stools from 225 children (aged 2--17 years) hospitalized with diagnosed infectious hepatitis during the period of a seasonal rise in morbidity rate yielded positive findings at an average rate of 10.5%. This rate also depended on the severity of the disease and the patient's age. The results obtained indicated that patients with infectious hepatitis could shed the virus for a long time (about 2 weeks) after the onset of the disease. Patients with the atypical, or anicteric, form of the disease could be equally considered a source of virus shedding. The prolonged excretion of viral particles did not correlate with delayed IgM response. The particles identified as hepatitis A virus seemed to be antigenically very close, if not identical, to the virus circulating in some other countries (USA, Australia, West Germany).", "contents": "[Experience in examining infectious hepatitis patients by using a viral detection method]. Immune electron microscopy was shown to be an acceptable diagnostic method which allowed to detect hepatitis A virus particles in the stools of patients with infectious hepatitis even at the late stages of the disease. The examination of stools from 225 children (aged 2--17 years) hospitalized with diagnosed infectious hepatitis during the period of a seasonal rise in morbidity rate yielded positive findings at an average rate of 10.5%. This rate also depended on the severity of the disease and the patient's age. The results obtained indicated that patients with infectious hepatitis could shed the virus for a long time (about 2 weeks) after the onset of the disease. Patients with the atypical, or anicteric, form of the disease could be equally considered a source of virus shedding. The prolonged excretion of viral particles did not correlate with delayed IgM response. The particles identified as hepatitis A virus seemed to be antigenically very close, if not identical, to the virus circulating in some other countries (USA, Australia, West Germany)."}
{"id": "PMID:224628", "title": "[Neurologic complications following medical treatment of epileptic patients].", "content": "Neurological complications due to anticonvulsive treatment was analyzed in 48 epileptic patients. It is demonstrated that there is a changed structure and increased frequency of epileptic paroxysms in appearance of neurological complications. Special attention is drawn to the significance of residual signs in organic diseases and to their occurrence. Recommendations are given for prevention and treatment of complications.", "contents": "[Neurologic complications following medical treatment of epileptic patients]. Neurological complications due to anticonvulsive treatment was analyzed in 48 epileptic patients. It is demonstrated that there is a changed structure and increased frequency of epileptic paroxysms in appearance of neurological complications. Special attention is drawn to the significance of residual signs in organic diseases and to their occurrence. Recommendations are given for prevention and treatment of complications."}
{"id": "PMID:224630", "title": "Ultrastructure of synapses in the central nervous system of lamellibranch molluscs.", "content": "Fine-structural characteristics of synaptic contacts were investigated in the central nervous system of different species of lamellibranch molluscs. Neuropile of the ganglia is characterized by regular occurrence of ultrastructurally well-defined polarized chemical synapses resembling those described in other invertebrate species and vertebrates. In addition to the generally observed membrane thickenings, enhanced density of synaptic membranes, cleft material and vesicle clustering on the presynaptic membrane, synapses are occasionally characterized by other and pinocytotic invaginations. Synaptic connections were distinguished on the basis of the vesicle content of the presynaptic terminal. Different forms of synaptic configurations (divergence, convergence, presynaptic modification) were observed in the ganglia.", "contents": "Ultrastructure of synapses in the central nervous system of lamellibranch molluscs. Fine-structural characteristics of synaptic contacts were investigated in the central nervous system of different species of lamellibranch molluscs. Neuropile of the ganglia is characterized by regular occurrence of ultrastructurally well-defined polarized chemical synapses resembling those described in other invertebrate species and vertebrates. In addition to the generally observed membrane thickenings, enhanced density of synaptic membranes, cleft material and vesicle clustering on the presynaptic membrane, synapses are occasionally characterized by other and pinocytotic invaginations. Synaptic connections were distinguished on the basis of the vesicle content of the presynaptic terminal. Different forms of synaptic configurations (divergence, convergence, presynaptic modification) were observed in the ganglia."}
{"id": "PMID:224632", "title": "Effects of an intravenous injection of tetracosactid on plasma corticosteroid and testosterone levels in unstressed male rabbits.", "content": "Administration of tetracosactid into male rabbits, fitted with permanently indwelling jugular catheters, resulted in a rapid rise of plasma corticosteroids and plasma testosterone. Corticosteroid concentrations were significantly elevated at 40 and 60 min and testosterone concentrations 20 min after the iv injection of tetracosactid (2.5, 5.0, and 10.0 micrograms/kg body weight), in comparison to pre-treatment levels. Corticosteroid values in plasma were elevated as long as 120 min after tetracosactid injection. In contrast, testosterone levels were lower at 60-120 min after tetracosactid injection than corresponding pre-treatment values. However, these differences were not significant. At the doses used no tetracosactid-dose-dependent corticosteroid or testosterone release could be found; apparently, testosterone release is only dependent upon basal plasma levels but not upon the dose of tetracosactid applied. From these studies it is concluded that tetracosactid may bring about an increase or decrease of testosterone concentration in plasma in the buck depending upon the length of time elapsing between injection of tetracosactid and blood withdrawal.", "contents": "Effects of an intravenous injection of tetracosactid on plasma corticosteroid and testosterone levels in unstressed male rabbits. Administration of tetracosactid into male rabbits, fitted with permanently indwelling jugular catheters, resulted in a rapid rise of plasma corticosteroids and plasma testosterone. Corticosteroid concentrations were significantly elevated at 40 and 60 min and testosterone concentrations 20 min after the iv injection of tetracosactid (2.5, 5.0, and 10.0 micrograms/kg body weight), in comparison to pre-treatment levels. Corticosteroid values in plasma were elevated as long as 120 min after tetracosactid injection. In contrast, testosterone levels were lower at 60-120 min after tetracosactid injection than corresponding pre-treatment values. However, these differences were not significant. At the doses used no tetracosactid-dose-dependent corticosteroid or testosterone release could be found; apparently, testosterone release is only dependent upon basal plasma levels but not upon the dose of tetracosactid applied. From these studies it is concluded that tetracosactid may bring about an increase or decrease of testosterone concentration in plasma in the buck depending upon the length of time elapsing between injection of tetracosactid and blood withdrawal."}
{"id": "PMID:224633", "title": "Replacement oral ethinyloestradiol therapy for gonadal dysgenesis: growth and adrenal androgen studies.", "content": "We have studied growth and adrenal dehydroepiandrosterone (DHA) responses to iv synthetic adrenocorticotrophic hormone (ACTH, Cortrosyn) in 6 girls with gonadal dysgenesis before and during treatment with low-dose ethinyloestradiol (EOe2). In all patients there was a statisfactory induction of secondary sexual characteristics including increase in breasts and public hair and onset of withdrawal bleeding within 6 months of therapy. Height velocity increased from 2.8 +/- 0.9 cm/year pre-treatment to 5.3 +/- 1.5 cm/year (P less than 0.02) in the first year. There was deceleration to 1.9 +/- 1.1 cm/year in the second year. There was no disproportionate advancement in bone age and thus, presumably, no loss of ultimate height. We could demonstrate no change in basal or ACTH-stimulated levels of DHA, a specific adrenal androgen, to account for the increased public hair and growth in these patients.", "contents": "Replacement oral ethinyloestradiol therapy for gonadal dysgenesis: growth and adrenal androgen studies. We have studied growth and adrenal dehydroepiandrosterone (DHA) responses to iv synthetic adrenocorticotrophic hormone (ACTH, Cortrosyn) in 6 girls with gonadal dysgenesis before and during treatment with low-dose ethinyloestradiol (EOe2). In all patients there was a statisfactory induction of secondary sexual characteristics including increase in breasts and public hair and onset of withdrawal bleeding within 6 months of therapy. Height velocity increased from 2.8 +/- 0.9 cm/year pre-treatment to 5.3 +/- 1.5 cm/year (P less than 0.02) in the first year. There was deceleration to 1.9 +/- 1.1 cm/year in the second year. There was no disproportionate advancement in bone age and thus, presumably, no loss of ultimate height. We could demonstrate no change in basal or ACTH-stimulated levels of DHA, a specific adrenal androgen, to account for the increased public hair and growth in these patients."}
{"id": "PMID:224634", "title": "Receptors for gonadotrophin and prostaglandin F2 alpha in bovine corpora lutea of early, mid and late luteal phase.", "content": "A total of 15 corpora lutea representing early (day 3), mid (day 13) and late luteal phase (day 20 and 21-24) were obtained by ovariectomy on cycling cows. The luteal weights and peripheral plasma progesterone levels just prior to ovariectomy, were consistent with the above luteal phases. The specific binding of [125I]human chorionic gonadotrophin to membranes prepared from corpora lutea was significantly higher (P less than 0.01) for days 13 and 20 than for days 3 and 21-24. The binding in day 21-24 corpora lutea was higher (P less than 0.01) than day 3. Although there was no different either in number or affinity (apparent dissociation constant (Kd) = 0.04 nM) of gonadotrophin receptors in days 13 and 20 corpora lutea, only in the former did the binding correlate well with plasma progesterone levels. The specific binding of [3H]prostaglanding (PG)F2 alpha to the membranes of the same corpora lutea showed a progressive increase (P less than 0.01) from day 3, reached the highest value at a time when corpora lutea were actively regressing (day 20) and the decline (P less than 0.01) by day 21-24. Although a considerable number of PGF2 alpha receptors existed at day 13, the affinity of these same receptors was 203 times lower (Kd = 3458 nM) than the affinity of receptors in day 20 corpora lutea (Kd = 17 nM). In summary, the above results show that gonadotrophin receptors correlate with luteotrophic, whereas PGF2 alpha receptors correlate with luteolytic phases in bovine corpora lutea.", "contents": "Receptors for gonadotrophin and prostaglandin F2 alpha in bovine corpora lutea of early, mid and late luteal phase. A total of 15 corpora lutea representing early (day 3), mid (day 13) and late luteal phase (day 20 and 21-24) were obtained by ovariectomy on cycling cows. The luteal weights and peripheral plasma progesterone levels just prior to ovariectomy, were consistent with the above luteal phases. The specific binding of [125I]human chorionic gonadotrophin to membranes prepared from corpora lutea was significantly higher (P less than 0.01) for days 13 and 20 than for days 3 and 21-24. The binding in day 21-24 corpora lutea was higher (P less than 0.01) than day 3. Although there was no different either in number or affinity (apparent dissociation constant (Kd) = 0.04 nM) of gonadotrophin receptors in days 13 and 20 corpora lutea, only in the former did the binding correlate well with plasma progesterone levels. The specific binding of [3H]prostaglanding (PG)F2 alpha to the membranes of the same corpora lutea showed a progressive increase (P less than 0.01) from day 3, reached the highest value at a time when corpora lutea were actively regressing (day 20) and the decline (P less than 0.01) by day 21-24. Although a considerable number of PGF2 alpha receptors existed at day 13, the affinity of these same receptors was 203 times lower (Kd = 3458 nM) than the affinity of receptors in day 20 corpora lutea (Kd = 17 nM). In summary, the above results show that gonadotrophin receptors correlate with luteotrophic, whereas PGF2 alpha receptors correlate with luteolytic phases in bovine corpora lutea."}
{"id": "PMID:224635", "title": "Thermal stability of F-actin as studied by spin labelling.", "content": "An analysis of the EPR spectra of maleimide spin-labelled actin was undertaken. We estimated a rotational correlation time of (13 +/- 2) nsec for the five-membered maleimide spin label bound to G-actin. The polarity of the environment of the bound labels indicated a strong polar character. The temperature dependence of the EPR spectral parameters of the attached label for F-actin exhibited rapid changes between 60-70 degrees C, which might be due to changes of protein structure. The conformational changes were reversible below 65 degrees C. The spin label spectra showed that the polymerization and depolymerization could be accomplished on actin thermally treated in F-form for 10 minutes at a temperature not higher than 60 degrees C. The findings suggest thermal stability of the spin-labelled sites in F-actin below 65 degrees C.", "contents": "Thermal stability of F-actin as studied by spin labelling. An analysis of the EPR spectra of maleimide spin-labelled actin was undertaken. We estimated a rotational correlation time of (13 +/- 2) nsec for the five-membered maleimide spin label bound to G-actin. The polarity of the environment of the bound labels indicated a strong polar character. The temperature dependence of the EPR spectral parameters of the attached label for F-actin exhibited rapid changes between 60-70 degrees C, which might be due to changes of protein structure. The conformational changes were reversible below 65 degrees C. The spin label spectra showed that the polymerization and depolymerization could be accomplished on actin thermally treated in F-form for 10 minutes at a temperature not higher than 60 degrees C. The findings suggest thermal stability of the spin-labelled sites in F-actin below 65 degrees C."}
{"id": "PMID:224631", "title": "[Surgical treatment of tumors of the parotid gland (author's transl)].", "content": "One hundred and thirty-one cases of patients operated for a parotidal tumor were reviewed. We report on 85 cases that had no previous treatment, including 68 benign and 17 malignant tumors. The surgical treatment applied is analysed according to the benign or malignant nature of the tumor and to the results. For benign mixed tumors (43 cases) there were 29 total resections, 12 superficial lobectomies and 2 simple enucleations (intraparotidal location unforseen). For tumors of Warthin (19 cases) the treatment was a superficial lobectomy in all cases. For malignant tumors (17 cases) 5 superficial lobectomies and 12 total resections of the gland were performed. In the latter, the facial nerve was severed in 6 patients and left intact in the other 6. The minimal operation realizing the resection of a parotidal tumor, is the superficial lobectomy realized in once, the deep lobe only being resected if invaded. Preservation of the facial nerve should always be tried, sacrificing it only in cases of infiltrating malignant tumor.", "contents": "[Surgical treatment of tumors of the parotid gland (author's transl)]. One hundred and thirty-one cases of patients operated for a parotidal tumor were reviewed. We report on 85 cases that had no previous treatment, including 68 benign and 17 malignant tumors. The surgical treatment applied is analysed according to the benign or malignant nature of the tumor and to the results. For benign mixed tumors (43 cases) there were 29 total resections, 12 superficial lobectomies and 2 simple enucleations (intraparotidal location unforseen). For tumors of Warthin (19 cases) the treatment was a superficial lobectomy in all cases. For malignant tumors (17 cases) 5 superficial lobectomies and 12 total resections of the gland were performed. In the latter, the facial nerve was severed in 6 patients and left intact in the other 6. The minimal operation realizing the resection of a parotidal tumor, is the superficial lobectomy realized in once, the deep lobe only being resected if invaded. Preservation of the facial nerve should always be tried, sacrificing it only in cases of infiltrating malignant tumor."}
{"id": "PMID:224637", "title": "Fingerprint inclusions and circular structures in the muscle. Report of a case.", "content": "Fingerprint inclusions, circular structures of unknown origin, mitochondrial changes, dilatation of the sarcoplasmic reticulum, rods of Z-line material, elongated T-systems, honeycombs, and myelin figures were present in some damaged muscle fibres. Many damaged fibres showed loss of myofilaments and groups of atrophied fibres occurred. The muscle biopsy was from the left biceps brachii and presented also the changes of polymyositis. The patient had muscle weakness, malignant hypertension, alcoholism, polyarthropathy, and evidence of mild peripheral neuropathy.", "contents": "Fingerprint inclusions and circular structures in the muscle. Report of a case. Fingerprint inclusions, circular structures of unknown origin, mitochondrial changes, dilatation of the sarcoplasmic reticulum, rods of Z-line material, elongated T-systems, honeycombs, and myelin figures were present in some damaged muscle fibres. Many damaged fibres showed loss of myofilaments and groups of atrophied fibres occurred. The muscle biopsy was from the left biceps brachii and presented also the changes of polymyositis. The patient had muscle weakness, malignant hypertension, alcoholism, polyarthropathy, and evidence of mild peripheral neuropathy."}
{"id": "PMID:224638", "title": "Studies on the early changes in acute isoniazid neuropathy in the rat.", "content": "Large single doses if isoniazid by mouth (1--2g/kg) have been shown to produce in rats Wallerian degeneration visible with the light microscope from the third day onwards. By contrast, changes in axons are seen from 24 h onwards by electron microscopy. The earliest ultrastructural changes are associated with vacuoles appearing between axon and Schwann cells. These are large and focal, and often compress the axon. The adjacent axon may show changes in smooth ER, and in microtubular arrangement. Alterations in smooth membranes and in mitochondria are visible in Schwann cell cytoplasm, not necessarily related to the vacuole formation and axonal features. It is suggested that INH neuropathy is essentially a multifocal axonal lesion.", "contents": "Studies on the early changes in acute isoniazid neuropathy in the rat. Large single doses if isoniazid by mouth (1--2g/kg) have been shown to produce in rats Wallerian degeneration visible with the light microscope from the third day onwards. By contrast, changes in axons are seen from 24 h onwards by electron microscopy. The earliest ultrastructural changes are associated with vacuoles appearing between axon and Schwann cells. These are large and focal, and often compress the axon. The adjacent axon may show changes in smooth ER, and in microtubular arrangement. Alterations in smooth membranes and in mitochondria are visible in Schwann cell cytoplasm, not necessarily related to the vacuole formation and axonal features. It is suggested that INH neuropathy is essentially a multifocal axonal lesion."}
{"id": "PMID:224639", "title": "Histopathology of the lens capsule in fibrillopathia epitheliocapsularis (FEC) or so-called senile exfoliation or pseudoexfoliation. An electron microscopic study.", "content": "Twenty lenses from cataractous eyes have been subjected to enzymatic breakdown by collagenase and alpha-chymotrypsin in order to remove part of the lens capsule and the zonular apparatus. Twelve of the lenses had clinical fibrillopathia epitheliocapsularis (FEC syndrome). In addition four FEC lenses and four ordinary cataractous lenses served as controls. A characteristic fibrillar substance was found in the FEC lenses located to circular epithelium-near areas varying in size from 10 micrometers to 150 micrometers. The circular areas were found in zona germinativa in front of the bow region and corresponded to the discoid plaques of the deep layer. The ultrastructure of the finely fibrillar material of the deep layer were indistinguishable from that of the surface material of the peripheral band and the central disc. A connection between the discoid plaques of deep layer and the peripheral granular band were demonstrated in the form of radial \"cobble-stone\" sectors seen in partially digested FEC capsules. An increased amount of age dependent spindleshaped formed bodies were also found in FEC lenses. The evidence presented points towards a lenticular origin of the Busacca-bushes in the peripheral ganular band of the lens capsule.", "contents": "Histopathology of the lens capsule in fibrillopathia epitheliocapsularis (FEC) or so-called senile exfoliation or pseudoexfoliation. An electron microscopic study. Twenty lenses from cataractous eyes have been subjected to enzymatic breakdown by collagenase and alpha-chymotrypsin in order to remove part of the lens capsule and the zonular apparatus. Twelve of the lenses had clinical fibrillopathia epitheliocapsularis (FEC syndrome). In addition four FEC lenses and four ordinary cataractous lenses served as controls. A characteristic fibrillar substance was found in the FEC lenses located to circular epithelium-near areas varying in size from 10 micrometers to 150 micrometers. The circular areas were found in zona germinativa in front of the bow region and corresponded to the discoid plaques of the deep layer. The ultrastructure of the finely fibrillar material of the deep layer were indistinguishable from that of the surface material of the peripheral band and the central disc. A connection between the discoid plaques of deep layer and the peripheral granular band were demonstrated in the form of radial \"cobble-stone\" sectors seen in partially digested FEC capsules. An increased amount of age dependent spindleshaped formed bodies were also found in FEC lenses. The evidence presented points towards a lenticular origin of the Busacca-bushes in the peripheral ganular band of the lens capsule."}
{"id": "PMID:224640", "title": "The prognosis in congenital lower limb hypertrophy.", "content": "Twenty-eight patients with congenital total hypertrophy and ten patients with lower limb hypertrophy with congenital vascular abnormalities are reviewed. The pattern of increase in leg length discrepancy during growth and its influence on surgical management is discussed and the clinical features of the affected limbs are described. In congenital total hypertrophy the maximal increase in leg length discrepancy of more than 2.5 cm at age 4 years are likely to develop significant limb overgrowth that will require eventual surgical correction. In patients with congenital vascular abnormalities the change of leg length discrepancy was variable in degree and unpredictable in pattern, even in those with similar venous anomalies. The outcome for the limb was detergiography.", "contents": "The prognosis in congenital lower limb hypertrophy. Twenty-eight patients with congenital total hypertrophy and ten patients with lower limb hypertrophy with congenital vascular abnormalities are reviewed. The pattern of increase in leg length discrepancy during growth and its influence on surgical management is discussed and the clinical features of the affected limbs are described. In congenital total hypertrophy the maximal increase in leg length discrepancy of more than 2.5 cm at age 4 years are likely to develop significant limb overgrowth that will require eventual surgical correction. In patients with congenital vascular abnormalities the change of leg length discrepancy was variable in degree and unpredictable in pattern, even in those with similar venous anomalies. The outcome for the limb was detergiography."}
{"id": "PMID:224641", "title": "Primary carcinoma of the liver. A histological study of 52 cases from Denmark.", "content": "Among 7763 autopsies performed in Greater Copenhagen in 1973, there were 309 cases of cirrhosis of the liver and 52 cases of primary carcinoma of the liver (PCL). Of the latter, 45 were hepatocellular carcinoma (HCC), 4 combined HCC and cholangiocarcinoma (CCC) and 3 CCC. HCC was found in 7.8 per cent of the cirrhotic livers and was in 57.1 per cent accompagnied by cirrhosis. The criteria of WHO, Peters (modified) and Anthony were used for classification. The degree of differentiation of the tumours was estimated using the criteria of WHO and Edmondson. The apparently small number of CCC may be due to the fact that this tumour is often overdiagnosed at the expense of HCC. The incidence of combined tumours is probably higher than generally assumed. The reticulin stain was found very valuable in HCC, both for descriptive and diagnostic purposes. In contrast to the situation in sub-Saharan Africa where hepatitis B virus is incriminated as the most important etiologic factor of HCC, it was found in the present study that alcoholism was a very essential cause of cirrhosis and thereby of HCC.", "contents": "Primary carcinoma of the liver. A histological study of 52 cases from Denmark. Among 7763 autopsies performed in Greater Copenhagen in 1973, there were 309 cases of cirrhosis of the liver and 52 cases of primary carcinoma of the liver (PCL). Of the latter, 45 were hepatocellular carcinoma (HCC), 4 combined HCC and cholangiocarcinoma (CCC) and 3 CCC. HCC was found in 7.8 per cent of the cirrhotic livers and was in 57.1 per cent accompagnied by cirrhosis. The criteria of WHO, Peters (modified) and Anthony were used for classification. The degree of differentiation of the tumours was estimated using the criteria of WHO and Edmondson. The apparently small number of CCC may be due to the fact that this tumour is often overdiagnosed at the expense of HCC. The incidence of combined tumours is probably higher than generally assumed. The reticulin stain was found very valuable in HCC, both for descriptive and diagnostic purposes. In contrast to the situation in sub-Saharan Africa where hepatitis B virus is incriminated as the most important etiologic factor of HCC, it was found in the present study that alcoholism was a very essential cause of cirrhosis and thereby of HCC."}
{"id": "PMID:224644", "title": "Increased brain uptake of copper and zinc in mice caused by diethyldithiocarbamate.", "content": "Mice given 64CuCl2 and 65ZnCl2 (10 mumol/kg) were treated with sodium diethyldithiocarbamate (0.5 mmol/kg). The treatment increased the brain level of radioactive copper five-fold and that of radioactive zinc three-fold. Such redistribution of metal ions may be explained from the formation of lipophilic metal chelates. The increased brain levels may involve neurotoxic effects.", "contents": "Increased brain uptake of copper and zinc in mice caused by diethyldithiocarbamate. Mice given 64CuCl2 and 65ZnCl2 (10 mumol/kg) were treated with sodium diethyldithiocarbamate (0.5 mmol/kg). The treatment increased the brain level of radioactive copper five-fold and that of radioactive zinc three-fold. Such redistribution of metal ions may be explained from the formation of lipophilic metal chelates. The increased brain levels may involve neurotoxic effects."}
{"id": "PMID:224645", "title": "Effect of toxogonin and P2S on the toxicity of carbamates and organophosphorus compounds.", "content": "Toxogonin (80 mg/kg intraperitoneally) given 15 min. prior to the administration of organophosphorus insecticides dimethoate, malathion, parathion and azinphos-methyl, organophosphorus warfare agents soman and tabun, or carbamates physostigmine, pyridostigmine and aldicarb, reduced the toxicity in mice of these agents by increasing their LD50 dose 1.5-3 fold. The toxicity of the carbamate insecticide carbaryl, however, was significantly increased by toxogonin. Similar results were obtained for P2S (150 mg/kg intraperitoneally) with respect to the toxicity of dimethoate, soman and pyridostigmine, whereas no effect could be detected on the toxicity of tabun. Only a slight reduction in the toxicity of physostigmine was observed. The acetylcholinesterase activity in erythrocytes, cerebrum and diaphragm of surviving mice 20 hours after organophosphate intoxication was similar both in toxogonin and P2S treated animals and untreated animals.", "contents": "Effect of toxogonin and P2S on the toxicity of carbamates and organophosphorus compounds. Toxogonin (80 mg/kg intraperitoneally) given 15 min. prior to the administration of organophosphorus insecticides dimethoate, malathion, parathion and azinphos-methyl, organophosphorus warfare agents soman and tabun, or carbamates physostigmine, pyridostigmine and aldicarb, reduced the toxicity in mice of these agents by increasing their LD50 dose 1.5-3 fold. The toxicity of the carbamate insecticide carbaryl, however, was significantly increased by toxogonin. Similar results were obtained for P2S (150 mg/kg intraperitoneally) with respect to the toxicity of dimethoate, soman and pyridostigmine, whereas no effect could be detected on the toxicity of tabun. Only a slight reduction in the toxicity of physostigmine was observed. The acetylcholinesterase activity in erythrocytes, cerebrum and diaphragm of surviving mice 20 hours after organophosphate intoxication was similar both in toxogonin and P2S treated animals and untreated animals."}
{"id": "PMID:224647", "title": "The role of alpha-adrenergic receptors in the vasoconstrictor response induced by indomethacin in the kidney.", "content": "The effect of indomethacin, an inhibitor of prostaglandin (PG) synthesis, was studied on the renal circulation, Na+ and water excretion in anaesthesized dogs during alpha-receptor inhibition. Indomethacin decreased cortical blood flow (CBFcontr, 454 +/- 142; CBFindo, 332 +/- 51 ml per min per 100 g; p less than 0.02) as well as medullary blood flow (OMBFcontr, 339 +/- 95; OMBFindo, 183 +/- 46 ml per min per 100 g; p less than 0.001), salt and water excretion, further it caused a shift in the intrarenal blood flow distribution toward the cortex. Alpha-blockade prevented the indomethacin-induced vasoconstriction in the cortex (CBF alpha inhibition + indo, 455 +/- 76 ml per min per 100 g) but not in the medullar (OMBF alpha inhibition + indo, 259 +/- 102 ml per min per 100 g, p less than 0.05). Alpha-blockade failed to prevent the indomethacin-induced antidiuresis, antinatriuresis and the intrarenal blood flow redistribution. GFR remained unaffected in all three series of studies. Our experimental findings are in line with the presumption that alpha-receptors are involved in the renal circulatory changes caused by indomethacin, probably as a result of an enhanced NE release during the inhibition of PG production. A NE--PG feed back mechanism is suggested in the regulation of renal circulation. The reduction of salt and water output induced by indomethacin appears to be independent of the alterations in renal haemodynamics, and seems rather to be the result of enhanced Na+ reabsorption, predominantly at the distal segment of the nephron, in the absence of PG, and/or a direct action of indomethacin.", "contents": "The role of alpha-adrenergic receptors in the vasoconstrictor response induced by indomethacin in the kidney. The effect of indomethacin, an inhibitor of prostaglandin (PG) synthesis, was studied on the renal circulation, Na+ and water excretion in anaesthesized dogs during alpha-receptor inhibition. Indomethacin decreased cortical blood flow (CBFcontr, 454 +/- 142; CBFindo, 332 +/- 51 ml per min per 100 g; p less than 0.02) as well as medullary blood flow (OMBFcontr, 339 +/- 95; OMBFindo, 183 +/- 46 ml per min per 100 g; p less than 0.001), salt and water excretion, further it caused a shift in the intrarenal blood flow distribution toward the cortex. Alpha-blockade prevented the indomethacin-induced vasoconstriction in the cortex (CBF alpha inhibition + indo, 455 +/- 76 ml per min per 100 g) but not in the medullar (OMBF alpha inhibition + indo, 259 +/- 102 ml per min per 100 g, p less than 0.05). Alpha-blockade failed to prevent the indomethacin-induced antidiuresis, antinatriuresis and the intrarenal blood flow redistribution. GFR remained unaffected in all three series of studies. Our experimental findings are in line with the presumption that alpha-receptors are involved in the renal circulatory changes caused by indomethacin, probably as a result of an enhanced NE release during the inhibition of PG production. A NE--PG feed back mechanism is suggested in the regulation of renal circulation. The reduction of salt and water output induced by indomethacin appears to be independent of the alterations in renal haemodynamics, and seems rather to be the result of enhanced Na+ reabsorption, predominantly at the distal segment of the nephron, in the absence of PG, and/or a direct action of indomethacin."}
{"id": "PMID:224648", "title": "Cardiac output and peripheral resistance of swim-trained rats under urethan anesthesia.", "content": "Several circulatory variables were determined in control and swim-trained white rats under urethan anesthesia. Trained animals exhibited significantly lower heart rate and cardiac index and significantly higher peripheral resistance than control animals. Blood pressure, systolic index and left ventricular work output were not statistically different in the two groups. These results suggest an alteration of resting cardiovascular regulation in trained animals. Beta adrenergic mechanisms are suppressed by increased parasympathetic tone, and the resting circulatory balance is maintained mainly by increased alfa adrenergic mechanisms.", "contents": "Cardiac output and peripheral resistance of swim-trained rats under urethan anesthesia. Several circulatory variables were determined in control and swim-trained white rats under urethan anesthesia. Trained animals exhibited significantly lower heart rate and cardiac index and significantly higher peripheral resistance than control animals. Blood pressure, systolic index and left ventricular work output were not statistically different in the two groups. These results suggest an alteration of resting cardiovascular regulation in trained animals. Beta adrenergic mechanisms are suppressed by increased parasympathetic tone, and the resting circulatory balance is maintained mainly by increased alfa adrenergic mechanisms."}
{"id": "PMID:224649", "title": "Effects of macrophages in resistance to murine cytomegalovirus infection.", "content": "In a preliminary experiment, the protective effects of peritoneal macrophages was shown by transferring macrophages from adult mice to newborn and to 7 and 14 days old mice. It was demonstrated that such transplantation protect suckling mice from intraperitoneal infection with MCMV by reducing the mortality rate from 100% to 27%.", "contents": "Effects of macrophages in resistance to murine cytomegalovirus infection. In a preliminary experiment, the protective effects of peritoneal macrophages was shown by transferring macrophages from adult mice to newborn and to 7 and 14 days old mice. It was demonstrated that such transplantation protect suckling mice from intraperitoneal infection with MCMV by reducing the mortality rate from 100% to 27%."}
{"id": "PMID:224650", "title": "Syncytia formation of human transformed cell lines by simian sarcoma virus type I (SSV-I/SSAV-I).", "content": "Human cells derived from malignant tumors (HeLa, HEp-2 and KB) and human cells transformed by tumor viruses (KCand RSb) formed syncytia by simian sarcoma virus type I (SSV-I/SSAV-I), but human diploid or non-transformed cells (WI-38, HEL and HEC) did not.", "contents": "Syncytia formation of human transformed cell lines by simian sarcoma virus type I (SSV-I/SSAV-I). Human cells derived from malignant tumors (HeLa, HEp-2 and KB) and human cells transformed by tumor viruses (KCand RSb) formed syncytia by simian sarcoma virus type I (SSV-I/SSAV-I), but human diploid or non-transformed cells (WI-38, HEL and HEC) did not."}
{"id": "PMID:224651", "title": "Demonstration of EBNA (Epstein-Barr virus nuclear antigen) antibodies of different immunoglobulin classes.", "content": "Anit-EBNA IgM, a previously unknown antibody, was detected by the antihuman globulin anticomplement immunofluorescence (ACIF) method in serum samples from acute infectious mononucleosis (IM) of Epstein-Barr virus (EBV) origin. The antibody disappears from the serum in some weeks during convalescence. It was absent in anti-EBV=positive sera of healthy donors and in serum samples taken from patients with IM caused by cytomegalo-virus. The antibody appears simultaneously with anti-EBV IgmM and, reaching a lower titre than the latter, its titre curve runs parallel with the anti-EBV IgM curve. Since in acute EBV infections, anti-EBNA IgM always appeared, its presence may serve as an additional evidence of the acuteness of EBV infection. In EBV-seropositive healthy subjects, the bulk of antibodies belongs to the IgG class, non-complement-fixing IgA antibodies occur only sporadically.", "contents": "Demonstration of EBNA (Epstein-Barr virus nuclear antigen) antibodies of different immunoglobulin classes. Anit-EBNA IgM, a previously unknown antibody, was detected by the antihuman globulin anticomplement immunofluorescence (ACIF) method in serum samples from acute infectious mononucleosis (IM) of Epstein-Barr virus (EBV) origin. The antibody disappears from the serum in some weeks during convalescence. It was absent in anti-EBV=positive sera of healthy donors and in serum samples taken from patients with IM caused by cytomegalo-virus. The antibody appears simultaneously with anti-EBV IgmM and, reaching a lower titre than the latter, its titre curve runs parallel with the anti-EBV IgM curve. Since in acute EBV infections, anti-EBNA IgM always appeared, its presence may serve as an additional evidence of the acuteness of EBV infection. In EBV-seropositive healthy subjects, the bulk of antibodies belongs to the IgG class, non-complement-fixing IgA antibodies occur only sporadically."}
{"id": "PMID:224652", "title": "Transformation of hamster embryonic fibroblast cells by UV-irradiated human cytomegalovirus.", "content": "Infection of hamster embryonic fibroblast (HEF) cells with UV-irradiated human CMV resulted in appearance of transformed clones. The established cell line (87-TRH-5) when inoculated subcutaneously induced tumour in newborn hamsters. The 87-TRH-5 cell line and the cell lines (87-TRH-5-Tsc1, 87-TRH-5-Tsc2, 87TRH-5-Tsc3) developed from the induced tumour, proved to bear CMV-spcific cytoplasmic and surface antigens. Demonstration of infectious CMV or MCV-specific nuclear antigen in 87-THR-5-cells has failed.", "contents": "Transformation of hamster embryonic fibroblast cells by UV-irradiated human cytomegalovirus. Infection of hamster embryonic fibroblast (HEF) cells with UV-irradiated human CMV resulted in appearance of transformed clones. The established cell line (87-TRH-5) when inoculated subcutaneously induced tumour in newborn hamsters. The 87-TRH-5 cell line and the cell lines (87-TRH-5-Tsc1, 87-TRH-5-Tsc2, 87TRH-5-Tsc3) developed from the induced tumour, proved to bear CMV-spcific cytoplasmic and surface antigens. Demonstration of infectious CMV or MCV-specific nuclear antigen in 87-THR-5-cells has failed."}
{"id": "PMID:224653", "title": "Neoplastic response of turkey liver to MC29 leukosis virus.", "content": "Twelve to fourteen days after intravenous inoculation of MC29 virus (1 x 10(5)LD50) into 1-day-old turkeys, liver tumour developed in 100% of the infected animals and led to death of birds. The tumour proved to be hepatomas histologically and electron microscopically. Numerous C-type particles were detectable among the tumour cells, as well as budding from the cell membrane. C-type particles were also observed in the tumour-free liver tissue in the spaces between the cells, budding was not detectable. Large number of virus particles were found in spleen extracellularly and intracellular vacuoles. Kidney tumours did not develop, but a few extracellular virus particles were located in the tissue. The MC29 virus-induced primary liver tumour in the turkey seems to be a suitable model for the morphological study of the relationship between oncogenic viruses and eukaryotic cells.", "contents": "Neoplastic response of turkey liver to MC29 leukosis virus. Twelve to fourteen days after intravenous inoculation of MC29 virus (1 x 10(5)LD50) into 1-day-old turkeys, liver tumour developed in 100% of the infected animals and led to death of birds. The tumour proved to be hepatomas histologically and electron microscopically. Numerous C-type particles were detectable among the tumour cells, as well as budding from the cell membrane. C-type particles were also observed in the tumour-free liver tissue in the spaces between the cells, budding was not detectable. Large number of virus particles were found in spleen extracellularly and intracellular vacuoles. Kidney tumours did not develop, but a few extracellular virus particles were located in the tissue. The MC29 virus-induced primary liver tumour in the turkey seems to be a suitable model for the morphological study of the relationship between oncogenic viruses and eukaryotic cells."}
{"id": "PMID:224654", "title": "Experimental cerebral concussion. A histochemical study.", "content": "The activity of mitochondrial enzymes (succinic dehydrogenase and cytochrome oxidase) and enzymes associated with blood-brain barrier function (butyrylcholinesterase and alkaline phosphatase) in the CNS of rats was studied from 5 minutes to 62 hours after cerebral concussion. There was a transient increase in succinic dehydrogenase activity during the first hour after concussion in the neurons of the structures close to the impact. The alkaline phosphatase activity, strongly positive in the walls of normal blood vessels, decreased within five minutes after concussion; it virtually disappeared in 15 minutes but returned to normal level after 62 hours. These findings are in good correlation with previous electron microscopic observations. Their significance is discussed.", "contents": "Experimental cerebral concussion. A histochemical study. The activity of mitochondrial enzymes (succinic dehydrogenase and cytochrome oxidase) and enzymes associated with blood-brain barrier function (butyrylcholinesterase and alkaline phosphatase) in the CNS of rats was studied from 5 minutes to 62 hours after cerebral concussion. There was a transient increase in succinic dehydrogenase activity during the first hour after concussion in the neurons of the structures close to the impact. The alkaline phosphatase activity, strongly positive in the walls of normal blood vessels, decreased within five minutes after concussion; it virtually disappeared in 15 minutes but returned to normal level after 62 hours. These findings are in good correlation with previous electron microscopic observations. Their significance is discussed."}
{"id": "PMID:224659", "title": "Nerve cell calcium as a messenger for opiate and endorphin actions.", "content": "The studies outlined in this chapter provide convincing evidence for the role of calcium in pharmacological and biochemical actions of opiates on the central nervous system. The ability of the synaptosomes to accumulate excess calcium during narcotic exposure represents a singular major example of cellular adaptation at the level of the membrane. These findings together with the possibility that CDR and calcium may mediate a number of processes involving neurotransmitter activity provide many avenues for the future study of opiates and other central nervous system depressants.", "contents": "Nerve cell calcium as a messenger for opiate and endorphin actions. The studies outlined in this chapter provide convincing evidence for the role of calcium in pharmacological and biochemical actions of opiates on the central nervous system. The ability of the synaptosomes to accumulate excess calcium during narcotic exposure represents a singular major example of cellular adaptation at the level of the membrane. These findings together with the possibility that CDR and calcium may mediate a number of processes involving neurotransmitter activity provide many avenues for the future study of opiates and other central nervous system depressants."}
{"id": "PMID:224662", "title": "Histochemical localization of opiate receptors and the enkephalins.", "content": "It is possible to localize opiate receptors and opioid peptides by light microscopic histochemical methods. The receptors have been mapped by autoradiography with specifically bound 3H-diprenorphine. They are found in anatomical areas associated with physiologic functions known to be altered by opiate administration, as well as in other areas. There appear to be opiate receptors on axons and nerve terminals; some of these are probably for axo-axonic synapses in glomeruli. Some electrophysiologic studies are supportive of the autoradiographic results. Enkephalin-containing neurons can be revealed by immunohistochemistry. Often, although not always, the distribution of enkephalin-like immunoreactivity is similar to that of the opiate receptors. These results are compatible with the notion that the enkephalins are the endogenous substrates of the opiate receptors.", "contents": "Histochemical localization of opiate receptors and the enkephalins. It is possible to localize opiate receptors and opioid peptides by light microscopic histochemical methods. The receptors have been mapped by autoradiography with specifically bound 3H-diprenorphine. They are found in anatomical areas associated with physiologic functions known to be altered by opiate administration, as well as in other areas. There appear to be opiate receptors on axons and nerve terminals; some of these are probably for axo-axonic synapses in glomeruli. Some electrophysiologic studies are supportive of the autoradiographic results. Enkephalin-containing neurons can be revealed by immunohistochemistry. Often, although not always, the distribution of enkephalin-like immunoreactivity is similar to that of the opiate receptors. These results are compatible with the notion that the enkephalins are the endogenous substrates of the opiate receptors."}
{"id": "PMID:224674", "title": "The obesity of middle age: a common variety of Cushing's syndrome due to a chronic increase in adrenocorticotrophin (ACTH) and beta-endorphin activity.", "content": "The common obesity of middle age presents a set of features that strongly resembles the cardinal symptoms of Cushing's syndrome: obesity of the face (moon face), upper back (buffalo hump) and trunk (pot belly) accompanied by signs of protein-wasting. In non-obese individuals who remain at a constant weight throughout life, the proportion of adipose tissue increases with age at the expense of lean tissue loss. Thus, a mild version of Cushing's syndrome may be part of the normal aging process. A more intense version of this process may occur in overweight adults. Excess and chronic activity of two pituitary hormones may contribute to this adiposity. Both hormones are produced in the same pituitary cell by cleavage from a common large precursor known as pro-opiocortin. One hormone is adrenocorticotrophin (ACTH), which stimulates the release of the glucocorticoid hormones. These hormones promote the conversion of bodily proteins to glucose (gluconeogenesis). The other pituitary hormone is beta-endorphin, a stimulant of appetite that causes the release of insulin. This pancreatic hormone promotes the conversion of glucose and fatty acids to triglycerides (lipogenesis). Three different etiologies are suggested for the excessive and chronic action of these two pituitary hormones: tumors that increase the number of cells that synthesize pro-opiocortin; mutant strains that produce excessive amounts of ACTH and beta-endorphin such as the genetically obese mouse (ob/ob) and rat (fa/fa); and an age-determined shift in the type of cleavage enzymes present in the pro-opiocortin cell that favors ACTH and beta-endorphin production.", "contents": "The obesity of middle age: a common variety of Cushing's syndrome due to a chronic increase in adrenocorticotrophin (ACTH) and beta-endorphin activity. The common obesity of middle age presents a set of features that strongly resembles the cardinal symptoms of Cushing's syndrome: obesity of the face (moon face), upper back (buffalo hump) and trunk (pot belly) accompanied by signs of protein-wasting. In non-obese individuals who remain at a constant weight throughout life, the proportion of adipose tissue increases with age at the expense of lean tissue loss. Thus, a mild version of Cushing's syndrome may be part of the normal aging process. A more intense version of this process may occur in overweight adults. Excess and chronic activity of two pituitary hormones may contribute to this adiposity. Both hormones are produced in the same pituitary cell by cleavage from a common large precursor known as pro-opiocortin. One hormone is adrenocorticotrophin (ACTH), which stimulates the release of the glucocorticoid hormones. These hormones promote the conversion of bodily proteins to glucose (gluconeogenesis). The other pituitary hormone is beta-endorphin, a stimulant of appetite that causes the release of insulin. This pancreatic hormone promotes the conversion of glucose and fatty acids to triglycerides (lipogenesis). Three different etiologies are suggested for the excessive and chronic action of these two pituitary hormones: tumors that increase the number of cells that synthesize pro-opiocortin; mutant strains that produce excessive amounts of ACTH and beta-endorphin such as the genetically obese mouse (ob/ob) and rat (fa/fa); and an age-determined shift in the type of cleavage enzymes present in the pro-opiocortin cell that favors ACTH and beta-endorphin production."}
{"id": "PMID:224677", "title": "Glucocorticoid receptor inactivation and activation by phosphorylation mechanisms.", "content": "The specific glucocorticoid binding capacity of cytosol preparations is rapidly lost on incubation at 25 degrees in the absence of ligand. We have examined this process in cell-free preparations from rat thymus, rat liver and mouse fibroblasts (L 929 cells), and we have found that the unoccupied receptor is inactivated by endogenous enzymes to a form that does not bind steroids. The inactivation can be prevented by inhibitors of phosphatase action such as molybdate, fluoride and glucose-1-phosphate. On the basis of this type of evidence we propose that the receptor activity of cytosol can be rendered inactive by a dephosphorylation process. We have now been able to partially reactivate the receptor in both L cell and rat thymus cytosols in an ATP dependent manner. If fibroblast (L cell) cytosol is preincubated to permit receptor inactivation by endogenous enzyme, further inactivation can be prevented by the addition of 10 mM molybdate and reactivation of the binding capacity can be obtained by adding 5 to 10 mM ATP in addition to molybdate. ATP dependent activation is prevented with EDTA and this block is overcome by added magnesium. ADP, CTP, GTP, and UTP are inactive. After inactivating the glucocorticoid binding capacity of rat thymocyte cytosol by incubation for 45 minutes at 25 degrees, considerable reactivation is obtained by addition of dithiothreitol and ATP. This system does not absolutely require the presence of a phosphatase inhibitor in order to show activation. Thymocyte cytosol can also be activated to a steroid binding state by addition of DTT and heat-treated (90 degrees for 15 min.) cytosol from a variety of cell types. The heat-treated cytosol contains ATP, reducing equivalents, and a relatively small molecular weight heat-stable activator(s) that potentiates the reactivation process. Maximum receptor activation is obtained by adding dithiothreitol, heat-stable factor, ATP, and molybdate to the inactivated thymocyte cytosol.", "contents": "Glucocorticoid receptor inactivation and activation by phosphorylation mechanisms. The specific glucocorticoid binding capacity of cytosol preparations is rapidly lost on incubation at 25 degrees in the absence of ligand. We have examined this process in cell-free preparations from rat thymus, rat liver and mouse fibroblasts (L 929 cells), and we have found that the unoccupied receptor is inactivated by endogenous enzymes to a form that does not bind steroids. The inactivation can be prevented by inhibitors of phosphatase action such as molybdate, fluoride and glucose-1-phosphate. On the basis of this type of evidence we propose that the receptor activity of cytosol can be rendered inactive by a dephosphorylation process. We have now been able to partially reactivate the receptor in both L cell and rat thymus cytosols in an ATP dependent manner. If fibroblast (L cell) cytosol is preincubated to permit receptor inactivation by endogenous enzyme, further inactivation can be prevented by the addition of 10 mM molybdate and reactivation of the binding capacity can be obtained by adding 5 to 10 mM ATP in addition to molybdate. ATP dependent activation is prevented with EDTA and this block is overcome by added magnesium. ADP, CTP, GTP, and UTP are inactive. After inactivating the glucocorticoid binding capacity of rat thymocyte cytosol by incubation for 45 minutes at 25 degrees, considerable reactivation is obtained by addition of dithiothreitol and ATP. This system does not absolutely require the presence of a phosphatase inhibitor in order to show activation. Thymocyte cytosol can also be activated to a steroid binding state by addition of DTT and heat-treated (90 degrees for 15 min.) cytosol from a variety of cell types. The heat-treated cytosol contains ATP, reducing equivalents, and a relatively small molecular weight heat-stable activator(s) that potentiates the reactivation process. Maximum receptor activation is obtained by adding dithiothreitol, heat-stable factor, ATP, and molybdate to the inactivated thymocyte cytosol."}
{"id": "PMID:224680", "title": "Relationship between histamine-induced changes of cyclic AMP and mechanical activity on smooth muscle preparations of the guinea-pig ileum and the rabbit mesenteric artery.", "content": "On guinea-pig ileum and rabbit mesenteric artery contracted by high potassium (100 mM) histamine produced relaxations which were inhibited by the H2-receptor antagonist metiamide. These results are thus indicative for the role of H2-receptors in mediating relaxation and for H1-receptors in mediating contraction on smooth muscle. Time course studies for the relaxing and cyclic AMP responses to histamine showed that the cyclic AMP increase preceded the H2-receptor mediated relaxation. The cyclic AMP increase in response to histamine was prevented by metiamide, but remained unaffected by mepyramine on both the guinea-pig ileum and the rabbit mesenteric artery. In addition, dose-response curves obtained on the mesenteric artery demonstrated that the H2-receptor mediated depressor responses coincided with cyclic AMP increases. Thus, these results gave clear-cut evidence that cyclic AMP is an intracellular metabolic event only implicit in the H2-receptor mediated relaxation, but not in the H1-receptor mediated contraction on smooth muscle preparations.", "contents": "Relationship between histamine-induced changes of cyclic AMP and mechanical activity on smooth muscle preparations of the guinea-pig ileum and the rabbit mesenteric artery. On guinea-pig ileum and rabbit mesenteric artery contracted by high potassium (100 mM) histamine produced relaxations which were inhibited by the H2-receptor antagonist metiamide. These results are thus indicative for the role of H2-receptors in mediating relaxation and for H1-receptors in mediating contraction on smooth muscle. Time course studies for the relaxing and cyclic AMP responses to histamine showed that the cyclic AMP increase preceded the H2-receptor mediated relaxation. The cyclic AMP increase in response to histamine was prevented by metiamide, but remained unaffected by mepyramine on both the guinea-pig ileum and the rabbit mesenteric artery. In addition, dose-response curves obtained on the mesenteric artery demonstrated that the H2-receptor mediated depressor responses coincided with cyclic AMP increases. Thus, these results gave clear-cut evidence that cyclic AMP is an intracellular metabolic event only implicit in the H2-receptor mediated relaxation, but not in the H1-receptor mediated contraction on smooth muscle preparations."}
{"id": "PMID:224682", "title": "Effects of D-penicillamine on lymphocyte modulation of synovial collagenase production.", "content": "While D-Penicillamine is effective in the treatment of rheumatoid arthritis, its mechanism of action is unknown. In this study, effects of D-Penicillamine on collagenase production by adherent rheumatoid synovial cells were investigated. D-Penicillamine did not directly affect the synovial collagenase production. However, lymphocyte-free-supernatant (LFS) recovered from lymphocytes exposed to D-Penicillamine in vivo and in vitro significantly reduced collagenase production by adherent synovial cells. LFS from lymphocytes of normal subjects and from non-D-Penicillamine treated rheumatoid patients stimulated collagenase production. These investigations indicate that D-Pencillamine indirectly affects collagenase production by cultured synovial cells and suggests beneficial effects on controlling the primary disease process.", "contents": "Effects of D-penicillamine on lymphocyte modulation of synovial collagenase production. While D-Penicillamine is effective in the treatment of rheumatoid arthritis, its mechanism of action is unknown. In this study, effects of D-Penicillamine on collagenase production by adherent rheumatoid synovial cells were investigated. D-Penicillamine did not directly affect the synovial collagenase production. However, lymphocyte-free-supernatant (LFS) recovered from lymphocytes exposed to D-Penicillamine in vivo and in vitro significantly reduced collagenase production by adherent synovial cells. LFS from lymphocytes of normal subjects and from non-D-Penicillamine treated rheumatoid patients stimulated collagenase production. These investigations indicate that D-Pencillamine indirectly affects collagenase production by cultured synovial cells and suggests beneficial effects on controlling the primary disease process."}
{"id": "PMID:224683", "title": "Differential susceptibility of peripheral nerves of the hen to triorthocresyl phosphate and to trauma.", "content": "The nerve fibres of largest diameter and of greatest length are considered to be the most vulnerable to triorthocresyl phosphate (TOCP). In this study, the differential vulnerability of the particular sciatic nerve branches was determined in the course of TOCP neuropathy and of Wallerian degeneration. The branch innervating the lateral gastrocnemius muscle, made up predominantly of large-diameter fibres, proved most susceptible to TOCP. By contrast, after proximal sciatic-nerve transection, degeneration commenced in the lateral nerve of the third digit, containing long nerve fibres of small diameter.", "contents": "Differential susceptibility of peripheral nerves of the hen to triorthocresyl phosphate and to trauma. The nerve fibres of largest diameter and of greatest length are considered to be the most vulnerable to triorthocresyl phosphate (TOCP). In this study, the differential vulnerability of the particular sciatic nerve branches was determined in the course of TOCP neuropathy and of Wallerian degeneration. The branch innervating the lateral gastrocnemius muscle, made up predominantly of large-diameter fibres, proved most susceptible to TOCP. By contrast, after proximal sciatic-nerve transection, degeneration commenced in the lateral nerve of the third digit, containing long nerve fibres of small diameter."}
{"id": "PMID:224686", "title": "Effects of the vestibular system on human development, part 2: Effects of vestibular stimulation on mentally retarded, emotionally disturbed, and learning-disabled individuals.", "content": "In Part 1 of this two-part series, studies concerned with the effects of vestibular stimulation on human development and function were reviewed and some implications for therapy were suggested. In Part 2, three categories of dysfunction with possible links to the vestibular system are discussed. Studies in the category of mental retardation evaluate motor development and sensory preference. Possible vestibular associations with emotional disturbance are examined by review of studies concerned with etiology, motor activity, speech, and clinical observations. A brief review of studies concerned with early identification and speech and language factors of learning-disabled children constitutes the third category. Interpretations are drawn and some implications for therapy are made.", "contents": "Effects of the vestibular system on human development, part 2: Effects of vestibular stimulation on mentally retarded, emotionally disturbed, and learning-disabled individuals. In Part 1 of this two-part series, studies concerned with the effects of vestibular stimulation on human development and function were reviewed and some implications for therapy were suggested. In Part 2, three categories of dysfunction with possible links to the vestibular system are discussed. Studies in the category of mental retardation evaluate motor development and sensory preference. Possible vestibular associations with emotional disturbance are examined by review of studies concerned with etiology, motor activity, speech, and clinical observations. A brief review of studies concerned with early identification and speech and language factors of learning-disabled children constitutes the third category. Interpretations are drawn and some implications for therapy are made."}
{"id": "PMID:224687", "title": "Formation and fate of ethionine-induced cytoplasmic crystalloids in rat parotid acinar cells.", "content": "The formation and fate of cytoplasmic crystalloids in rat parotid acinar cells were investigated during ethionine intoxication and recovery. By day 3 of ethionine treatment, acinar cells had numerous autophagic vacuoles containing recognizable secretory granules and fragments of rough endoplasmic reticulum. By day 5, immature crystalloids were present in many of the autophagic vacuoles, and as the crystalloids matured, a 7-nm periodicity became apparent. Crystalloids were never observed in the Golgi saccules or in any other organelle associated with secretory granule formation. When ethionine treatment was stopped, the acinar cells rapidly returned to their normal morphology. The majority of the crystalloids and autophagic vacuoles were lost from the cells during the first two to three days of recovery. At this time annulate lamellae were present intracellularly, and macrophages, many containing crystalloids, were associated with the basal surface of the acinar cells. These results indicate that the cytoplasmic crystalloids are formed in autophagic vacuoles, and do not represent an abnormal secretory product. Additiontionally, during recovery crystalloids may be removed from the acinar cells by interaction with macrophages. The sequence of autophagic vacuole formation, development of crystalloids, macrophage infiltration and phagocytosis of acinar cell debris appears to be a non-specific response of the rat parotid gland to cellular injury occurring in a variety of experimental and pathological conditions.", "contents": "Formation and fate of ethionine-induced cytoplasmic crystalloids in rat parotid acinar cells. The formation and fate of cytoplasmic crystalloids in rat parotid acinar cells were investigated during ethionine intoxication and recovery. By day 3 of ethionine treatment, acinar cells had numerous autophagic vacuoles containing recognizable secretory granules and fragments of rough endoplasmic reticulum. By day 5, immature crystalloids were present in many of the autophagic vacuoles, and as the crystalloids matured, a 7-nm periodicity became apparent. Crystalloids were never observed in the Golgi saccules or in any other organelle associated with secretory granule formation. When ethionine treatment was stopped, the acinar cells rapidly returned to their normal morphology. The majority of the crystalloids and autophagic vacuoles were lost from the cells during the first two to three days of recovery. At this time annulate lamellae were present intracellularly, and macrophages, many containing crystalloids, were associated with the basal surface of the acinar cells. These results indicate that the cytoplasmic crystalloids are formed in autophagic vacuoles, and do not represent an abnormal secretory product. Additiontionally, during recovery crystalloids may be removed from the acinar cells by interaction with macrophages. The sequence of autophagic vacuole formation, development of crystalloids, macrophage infiltration and phagocytosis of acinar cell debris appears to be a non-specific response of the rat parotid gland to cellular injury occurring in a variety of experimental and pathological conditions."}
{"id": "PMID:224688", "title": "The isolation of single cells from the avian salt gland.", "content": "Collagenase, hyaluronidase, and trypsin were used to isolate single cells from the avian salt gland. Three cell types were distinquishable in the resultant cell suspension: peripheral, intermediate, and principal cells. The fine structure of these cells is described and related to the morphology of the intact gland.", "contents": "The isolation of single cells from the avian salt gland. Collagenase, hyaluronidase, and trypsin were used to isolate single cells from the avian salt gland. Three cell types were distinquishable in the resultant cell suspension: peripheral, intermediate, and principal cells. The fine structure of these cells is described and related to the morphology of the intact gland."}
{"id": "PMID:224689", "title": "Structure of the endodermal epithelium of the chick yolk sac during early stages of development.", "content": "The structure of the areas pellucida and vasculosa of the early chick embryo (stages 11-29) was examined by light, transmission and scanning electron microscopy. The most striking feature of the endodermal cells of these areas is the presence of large intracellular yolk drops which are characteristic of the regions in which they are found; lipid-like homogeneous drops in the area pellucida, heterogeneously composed pleomorphic drops in the mid-region of the area vasculosa and granular drops at the periphery of the area vasculosa in the region of the sinus terminalis. On morphological criteria it is postulated that granular drops may arise by direct engulfment of extracellular yolk, but this does not appear to be true for pleomorphic or homogeneous drops. Since the apical junctions between endodermal cells across the yolk sac are tight, they seal off the extraembryonic compartment from the vitelline circulation and presumably prevent intercellular passage of the yolk constituents. Thus the endodermal epithelium must mediate the transport of nutrients from the yolk mass to the developing embryo. Endodermal cells exhibit a variation across the yolk sac in the presence and number of structures associated with uptake of extracellular materials. The mid-region of the area vasculosa appears to be the most endocytotically active region with an abundance of microvilli, bristle-coated pits and vesicles and apical canaliculi and vacuoles. There is a close association between the endoderm and vitelline blood vessels and this association is maintained, as the yolk sac develops, by the formation of small vessels juxtaposed between the vascular surface of the endoderm and the walls of the large vitelline vessels.", "contents": "Structure of the endodermal epithelium of the chick yolk sac during early stages of development. The structure of the areas pellucida and vasculosa of the early chick embryo (stages 11-29) was examined by light, transmission and scanning electron microscopy. The most striking feature of the endodermal cells of these areas is the presence of large intracellular yolk drops which are characteristic of the regions in which they are found; lipid-like homogeneous drops in the area pellucida, heterogeneously composed pleomorphic drops in the mid-region of the area vasculosa and granular drops at the periphery of the area vasculosa in the region of the sinus terminalis. On morphological criteria it is postulated that granular drops may arise by direct engulfment of extracellular yolk, but this does not appear to be true for pleomorphic or homogeneous drops. Since the apical junctions between endodermal cells across the yolk sac are tight, they seal off the extraembryonic compartment from the vitelline circulation and presumably prevent intercellular passage of the yolk constituents. Thus the endodermal epithelium must mediate the transport of nutrients from the yolk mass to the developing embryo. Endodermal cells exhibit a variation across the yolk sac in the presence and number of structures associated with uptake of extracellular materials. The mid-region of the area vasculosa appears to be the most endocytotically active region with an abundance of microvilli, bristle-coated pits and vesicles and apical canaliculi and vacuoles. There is a close association between the endoderm and vitelline blood vessels and this association is maintained, as the yolk sac develops, by the formation of small vessels juxtaposed between the vascular surface of the endoderm and the walls of the large vitelline vessels."}
{"id": "PMID:224691", "title": "The effect of a natural high-fiber diet on serum lipids, fecal lipids, and colonic function.", "content": "In a cross-over experiment,  46 young healthy volunteers consumed in succession a high-fiber and a low-fiber diet for 3 weeks at two levels of dietary cholesterol. Half of the dietary fiber came from fruits and vegetables, and the rest from bread and other cereal products. On the high-fiber diet, concentrations of serum cholesterol decreased on average by 0.44 mmole/liter with high-cholesterol and 0.31 mmole/liter with low-cholesterol regimes; high density lipoprotein-cholesterole decreased by 0.1 mmole/liter; on average fecal weight increased by 115 g/day and mean transit time through the gut was decreased by 18 hr. Only part of the decrease in serum cholesterole may be due directly to the high intake of dietary fiber components. The remainder is due to differences in fat intake: during the high-fiber period subjects consumed less fat and cholesterol than had been planned.", "contents": "The effect of a natural high-fiber diet on serum lipids, fecal lipids, and colonic function. In a cross-over experiment,  46 young healthy volunteers consumed in succession a high-fiber and a low-fiber diet for 3 weeks at two levels of dietary cholesterol. Half of the dietary fiber came from fruits and vegetables, and the rest from bread and other cereal products. On the high-fiber diet, concentrations of serum cholesterol decreased on average by 0.44 mmole/liter with high-cholesterol and 0.31 mmole/liter with low-cholesterol regimes; high density lipoprotein-cholesterole decreased by 0.1 mmole/liter; on average fecal weight increased by 115 g/day and mean transit time through the gut was decreased by 18 hr. Only part of the decrease in serum cholesterole may be due directly to the high intake of dietary fiber components. The remainder is due to differences in fat intake: during the high-fiber period subjects consumed less fat and cholesterol than had been planned."}
{"id": "PMID:224693", "title": "Infectious mononucleosis test performance on CAP survey specimens.", "content": "The participant performances on 1977 and 1978 infectious mononucleosis survey specimens are tabulated. The various methods utilized gave similar results on negative specimens. Commercial reagent kits incorporating differential absorption performed somewhat better on positive specimens than kits without differential absorption. Many of the commercial reagent kits performed very poorly on the false postitive specimen.", "contents": "Infectious mononucleosis test performance on CAP survey specimens. The participant performances on 1977 and 1978 infectious mononucleosis survey specimens are tabulated. The various methods utilized gave similar results on negative specimens. Commercial reagent kits incorporating differential absorption performed somewhat better on positive specimens than kits without differential absorption. Many of the commercial reagent kits performed very poorly on the false postitive specimen."}
{"id": "PMID:224694", "title": "Somatomedin and growth hormone studies in pediatric renal allograft recipients who receive daily prednisone.", "content": "Plasma somatomedin (SM) activity and growth hormone (GH) concentration were measured in ten growth-retarded, well-nourished pediatric renal allograft recipients who received daily prednisone therapy. The SM activity ranged from 0.21 to 1.22 micron/mL, and it was subnormal in three patients. A significant correlation was found between SM activity and creatinine clearance. Serial SM levels were determined during a 24-hour period in five patients; SM activity decreased at six and 12 hours and returned to normal values by 24 hours. The 24-hour plasma GH concentrations ranged from 1.5 to 7.6 mg/mL. Peak GH concentrations ranged from 2.1 to 14.2 ng/mL after insulin-induced hypoglycemia and from 1.8 to 24.6 ng/mL after oral glucose loading. Sleeping GH peaks were absent in two patients. These results suggest that growth failure in renal allograft recipients who receive daily prednisone may result from (1) partial GH deficiency, (2) reduced SM levels owing to diminished allograft function, and (3) daily transient decrease in plasma SM levels after prednisone administration.", "contents": "Somatomedin and growth hormone studies in pediatric renal allograft recipients who receive daily prednisone. Plasma somatomedin (SM) activity and growth hormone (GH) concentration were measured in ten growth-retarded, well-nourished pediatric renal allograft recipients who received daily prednisone therapy. The SM activity ranged from 0.21 to 1.22 micron/mL, and it was subnormal in three patients. A significant correlation was found between SM activity and creatinine clearance. Serial SM levels were determined during a 24-hour period in five patients; SM activity decreased at six and 12 hours and returned to normal values by 24 hours. The 24-hour plasma GH concentrations ranged from 1.5 to 7.6 mg/mL. Peak GH concentrations ranged from 2.1 to 14.2 ng/mL after insulin-induced hypoglycemia and from 1.8 to 24.6 ng/mL after oral glucose loading. Sleeping GH peaks were absent in two patients. These results suggest that growth failure in renal allograft recipients who receive daily prednisone may result from (1) partial GH deficiency, (2) reduced SM levels owing to diminished allograft function, and (3) daily transient decrease in plasma SM levels after prednisone administration."}
{"id": "PMID:224695", "title": "Surgical management of insulinoma.", "content": "Three patients with insulinoma have been presented. Accurate diagnosis, localization and multiplicity are possible employing angiography, sonography, CAT and insulin concentration determinations of specimens obtained by percutaneous, transhepatic simultaneous sampling of the portal, splenic and superior mesenteric veins. Meticulous exploration of the gland will permit enucleation rather than major resection to be a feasible solution and the operation of choice.", "contents": "Surgical management of insulinoma. Three patients with insulinoma have been presented. Accurate diagnosis, localization and multiplicity are possible employing angiography, sonography, CAT and insulin concentration determinations of specimens obtained by percutaneous, transhepatic simultaneous sampling of the portal, splenic and superior mesenteric veins. Meticulous exploration of the gland will permit enucleation rather than major resection to be a feasible solution and the operation of choice."}
{"id": "PMID:224696", "title": "Prevalence of antibody to hepatitis A and hepatitis B viruses in selected populations of the South Pacific.", "content": "Five island populations representing the three major cultural groups of the South Pacific--Polynesia, Micronesia, Melanesia--were studied for prevalence of antibody to hepatitis A virus (anti-HAV) and of antibody to the core antigen of hepatitis B virus (anti-HBc). Sera were collected in the late 1950s and early 1960s, selected where possible for appropriate age and sex distributions, and were tested by radioimmunoassay. Rather marked differences in prevalence were observed. Anti-HBc patterns confirmed that HBV is endemic in the Pacific populations. Furthermore, the patterns differed somewhat from each other and did not correlate with ethnogeographic area. Prevalence of anti-HAV was high in all populations studied. A Unique pattern was found for the island of Ponape (Micronesia): In a Ponape population bled in 1963, anti-HAV was not detected in any individual under 20 years of age, but almost all individuals over that age were found to be seropositive. On testing a second group of sera collected in 1975, all individuals aged 14--21 years were found to be antibody positive, indicating that HAV had returned to Ponape sometime prior to 1975. There was no significant difference in the prevalence of HAV or HBV infection between males and females in any of the populations studied.", "contents": "Prevalence of antibody to hepatitis A and hepatitis B viruses in selected populations of the South Pacific. Five island populations representing the three major cultural groups of the South Pacific--Polynesia, Micronesia, Melanesia--were studied for prevalence of antibody to hepatitis A virus (anti-HAV) and of antibody to the core antigen of hepatitis B virus (anti-HBc). Sera were collected in the late 1950s and early 1960s, selected where possible for appropriate age and sex distributions, and were tested by radioimmunoassay. Rather marked differences in prevalence were observed. Anti-HBc patterns confirmed that HBV is endemic in the Pacific populations. Furthermore, the patterns differed somewhat from each other and did not correlate with ethnogeographic area. Prevalence of anti-HAV was high in all populations studied. A Unique pattern was found for the island of Ponape (Micronesia): In a Ponape population bled in 1963, anti-HAV was not detected in any individual under 20 years of age, but almost all individuals over that age were found to be seropositive. On testing a second group of sera collected in 1975, all individuals aged 14--21 years were found to be antibody positive, indicating that HAV had returned to Ponape sometime prior to 1975. There was no significant difference in the prevalence of HAV or HBV infection between males and females in any of the populations studied."}
{"id": "PMID:224697", "title": "A seroepidemiologic study of infection with HAV and HBV in five Pacific Islands.", "content": "A batch of 1025 serum samples, obtained from healthy subjects and hospital patients from five Pacific islands (Viti Levu, Funafuti, Niue, Rarotonga and Upolu) were tested for antibody to hepatitis A virus (anti-HAV), hepatitis B surface antigen (HBsAG) and antibody to hepatitis B surface antigen (anti-HBs) by solid phase radioimmunoassay (SPRIA). High frequencies of anti-HAV were observed in each population (Funafuti, 79.9%; Upolu, 81.6%; Viti Levu, 84.3%; Rarotonga, 95.0%; and Niue, 95.2%), and the age-specific prevalence suggested that the majority of infections with this virus had occurred in the first decade of life. Hepatitis B was endemic in each population, although the total infection rates (as measured by the sum of HBsAG and anti-Hbs frequencies) were lower than for hepatitis A. While infections with each virus tended to run in parallel, peak prevalence of anti-HAV was usually reached in the second decade of life and peak prevalence of HBsAg and anti-HBs was not attained until a decade later. The pattern of infection with HBV was similar in each of the groups studied with the exception of Indians living in Viti Levu, among whom unusually low levels of antigen and antibody were demonstrated.", "contents": "A seroepidemiologic study of infection with HAV and HBV in five Pacific Islands. A batch of 1025 serum samples, obtained from healthy subjects and hospital patients from five Pacific islands (Viti Levu, Funafuti, Niue, Rarotonga and Upolu) were tested for antibody to hepatitis A virus (anti-HAV), hepatitis B surface antigen (HBsAG) and antibody to hepatitis B surface antigen (anti-HBs) by solid phase radioimmunoassay (SPRIA). High frequencies of anti-HAV were observed in each population (Funafuti, 79.9%; Upolu, 81.6%; Viti Levu, 84.3%; Rarotonga, 95.0%; and Niue, 95.2%), and the age-specific prevalence suggested that the majority of infections with this virus had occurred in the first decade of life. Hepatitis B was endemic in each population, although the total infection rates (as measured by the sum of HBsAG and anti-Hbs frequencies) were lower than for hepatitis A. While infections with each virus tended to run in parallel, peak prevalence of anti-HAV was usually reached in the second decade of life and peak prevalence of HBsAg and anti-HBs was not attained until a decade later. The pattern of infection with HBV was similar in each of the groups studied with the exception of Indians living in Viti Levu, among whom unusually low levels of antigen and antibody were demonstrated."}
{"id": "PMID:224698", "title": "Comparative epidemiology of two rotavirus serotypes and other viral agents associated with pediatric gastroenteritis.", "content": "Human rotavirus (HRV) type 1 or 2, adenovirus, or non-cultivatable 27 nm virus-like particles were demonstrated by electron microscopy and/or rotavirus ELISA in fecal samples from 45.5% of 604 gastroenteritis inpatients, 25.0% of 200 gastroenteritis outpatients and 6.0% of 812 control subjects, all sampled at Children's Hospital National Medical Center. Washington, DC. Rotaviruses were the most common pathogens detected as 39% and 22% of gastroenteritis inpatients and outpatients, respectively, shed HRV. About three-fourths of the rotaviruses were type 2, which was prevalent during five successive epidemic years from January, 1974, through June, 1978. HRV type 1 was detected in the last four successive epidemic years and represented nearly half of the HRV infections observed among gastroenteritis inpatients during the year 1977--1978. Both rotavirus serotypes were detected most often in the month of January, when 71% of 123 gastroenteritis inpatients and 62% of 34 gastroenteritis outpatients shed one of these viruses. Uncultivatable adenoviruses were detected significantly more frequently in stools from patients with gastroenteritis (3.9%) than from control subjects (0.6%), suggesting that these viruses played a role in acute enteric disease. The frequency of detection of 27 nm particles was not significantly different in gastroenteritis and control patients. Numerically, HRV infection was detected most often in gastroenteritis inpatients who were 10 through 12 months of age. The group of gastroenteritis inpatients with the highest percentage of HRV infection was 13 through 15 months of age. The excess of type 2 HRV infection relative to type 1 infection was especially large in those aged 7 through 24 months. Lower socioeconomic status or greater crowding appeared to be associated with the occurrence of rotavirus infection earlier in life and earlier in the epidemic year.", "contents": "Comparative epidemiology of two rotavirus serotypes and other viral agents associated with pediatric gastroenteritis. Human rotavirus (HRV) type 1 or 2, adenovirus, or non-cultivatable 27 nm virus-like particles were demonstrated by electron microscopy and/or rotavirus ELISA in fecal samples from 45.5% of 604 gastroenteritis inpatients, 25.0% of 200 gastroenteritis outpatients and 6.0% of 812 control subjects, all sampled at Children's Hospital National Medical Center. Washington, DC. Rotaviruses were the most common pathogens detected as 39% and 22% of gastroenteritis inpatients and outpatients, respectively, shed HRV. About three-fourths of the rotaviruses were type 2, which was prevalent during five successive epidemic years from January, 1974, through June, 1978. HRV type 1 was detected in the last four successive epidemic years and represented nearly half of the HRV infections observed among gastroenteritis inpatients during the year 1977--1978. Both rotavirus serotypes were detected most often in the month of January, when 71% of 123 gastroenteritis inpatients and 62% of 34 gastroenteritis outpatients shed one of these viruses. Uncultivatable adenoviruses were detected significantly more frequently in stools from patients with gastroenteritis (3.9%) than from control subjects (0.6%), suggesting that these viruses played a role in acute enteric disease. The frequency of detection of 27 nm particles was not significantly different in gastroenteritis and control patients. Numerically, HRV infection was detected most often in gastroenteritis inpatients who were 10 through 12 months of age. The group of gastroenteritis inpatients with the highest percentage of HRV infection was 13 through 15 months of age. The excess of type 2 HRV infection relative to type 1 infection was especially large in those aged 7 through 24 months. Lower socioeconomic status or greater crowding appeared to be associated with the occurrence of rotavirus infection earlier in life and earlier in the epidemic year."}
{"id": "PMID:224699", "title": "The association of total cholesterol, triglycerides and plasma lipoprotein cholesterol levels in first degree relatives and spouse pairs.", "content": "HDL, VLDL, and LDL cholesterol as well as total cholesterol were measured in young adult offspring of Framingham Heart Study participants. Parental total cholesterol levels measured in the early 1950s were found to be significant predictors of present total cholesterol in the offspring. While both maternal and paternal cholesterol levels made an independent contribution to the prediction of the offspring's cholesterol, the mother's contribution was significantly greater than the father's for male offspring with a similar but less striking relationship for female offspring. The correlation for LDL cholesterol levels for siblings was higher than for HDL cholesterol or log VLDL choles terol. When adjustments were made for age, body weight, alcohol intake and cigarette smoking, slight reductions in the correlations were noted, but all adjusted correlations remained significantly different from zero. The spouse correlations for lipoproteins, however, did not differ from zero after adujustment. Since the significant association for lipoproteins in spouse pairs disappears on adjustment for correlates but the association for siblings does not, it is likely that the sibling lipoprotein associations result from either genetic or environmental factors shared early in life.", "contents": "The association of total cholesterol, triglycerides and plasma lipoprotein cholesterol levels in first degree relatives and spouse pairs. HDL, VLDL, and LDL cholesterol as well as total cholesterol were measured in young adult offspring of Framingham Heart Study participants. Parental total cholesterol levels measured in the early 1950s were found to be significant predictors of present total cholesterol in the offspring. While both maternal and paternal cholesterol levels made an independent contribution to the prediction of the offspring's cholesterol, the mother's contribution was significantly greater than the father's for male offspring with a similar but less striking relationship for female offspring. The correlation for LDL cholesterol levels for siblings was higher than for HDL cholesterol or log VLDL choles terol. When adjustments were made for age, body weight, alcohol intake and cigarette smoking, slight reductions in the correlations were noted, but all adjusted correlations remained significantly different from zero. The spouse correlations for lipoproteins, however, did not differ from zero after adujustment. Since the significant association for lipoproteins in spouse pairs disappears on adjustment for correlates but the association for siblings does not, it is likely that the sibling lipoprotein associations result from either genetic or environmental factors shared early in life."}
{"id": "PMID:224701", "title": "Familial absorptive hypercalciuria and renal tubular acidosis.", "content": "Hypercalciuria was considered as a secondary condition when associated with familial renal tubular acidosis. Later studies suggested that hypercalciuria could lead to renal tubular acidosis and nephrocalcinosis. Selected members of a family spanning five generations were studied. Renal tubular acidosis was present in eight subjects in three consecutive generations. Increased 24-hour urinary calcium excretion was present in nine subjects in three consecutive generations, alone in the younger generation, and in combination with renal tubular acidosis and nephrocalcinosis in the older generation. Calcium loading tests showed the absorptive nature of hypercalciuria in nine of 18 subjects studied. This report suggests that in this family the absorptive hypercalciuria is an autosomal dominant genetic defect with complete penetrance and variable expressivity which leads to renal tubular acidosis and nephrocalcinosis.", "contents": "Familial absorptive hypercalciuria and renal tubular acidosis. Hypercalciuria was considered as a secondary condition when associated with familial renal tubular acidosis. Later studies suggested that hypercalciuria could lead to renal tubular acidosis and nephrocalcinosis. Selected members of a family spanning five generations were studied. Renal tubular acidosis was present in eight subjects in three consecutive generations. Increased 24-hour urinary calcium excretion was present in nine subjects in three consecutive generations, alone in the younger generation, and in combination with renal tubular acidosis and nephrocalcinosis in the older generation. Calcium loading tests showed the absorptive nature of hypercalciuria in nine of 18 subjects studied. This report suggests that in this family the absorptive hypercalciuria is an autosomal dominant genetic defect with complete penetrance and variable expressivity which leads to renal tubular acidosis and nephrocalcinosis."}
{"id": "PMID:224705", "title": "Genital bacteriology: a comparative study of premenopausal women with postmenopausal women.", "content": "Premenopausal women are reportedly at a higher risk than postmenopausal women of postoperative infection following vaginal hysterectomy. A study was designed to determine whether a relationship exists between bacterial flora and patient age that may explain the difference in the risk of postoperative infection. No statistically significant difference was found in the number or type of bacterial species isolated from the cervix or vagina of premenopausal and postmenopausal women. Postmenopausal women on a regimen of conjugated estrogens had genital flora similar to that of the other women studied.", "contents": "Genital bacteriology: a comparative study of premenopausal women with postmenopausal women. Premenopausal women are reportedly at a higher risk than postmenopausal women of postoperative infection following vaginal hysterectomy. A study was designed to determine whether a relationship exists between bacterial flora and patient age that may explain the difference in the risk of postoperative infection. No statistically significant difference was found in the number or type of bacterial species isolated from the cervix or vagina of premenopausal and postmenopausal women. Postmenopausal women on a regimen of conjugated estrogens had genital flora similar to that of the other women studied."}
{"id": "PMID:224707", "title": "Polypeptide hormones in argentaffin and argyrophil gastroduodenal endocrine tumors.", "content": "The morphology and histochemistry of gastroduodenal endocrine tumors from 16 patients were studied. All patients underwent operation, in most cases with a preoperative diagnosis of nonendocrine tumor, ulcer, o polyp(s). The argentaffin reaction was positive in three tumors, and the Hellerstr\u00f6m--Hellman argyrophil reaction was positive in four tumors. All tumors reacted positively to the Grimelius argyrophil stain, and 13 were positive with the Sevier--Munger argyrophil stain. Gastrin immunoreactivity was found in eight tumors, and substance-P immunoreactivity in seven tumors. No enteroglucagon, adrenal cortex hormone, or pancreatic polypeptide was observed in any of the tumors. Three patients with Sevier--Munger-positive gastric tumors had concurrent pernicious anemia, and 2 patients with gastrin-immunoreactive tumors had acute or chronic gastroduodenal ulceration. The results indicate that the gastroduodenal endocrine tumor as a rule gives no endocrine symptoms and that the tumor type is an unexpected finding at operation. The tumors may contain gastrin, substance P, somatostatin, and serotonin and tend to be multihormonal.", "contents": "Polypeptide hormones in argentaffin and argyrophil gastroduodenal endocrine tumors. The morphology and histochemistry of gastroduodenal endocrine tumors from 16 patients were studied. All patients underwent operation, in most cases with a preoperative diagnosis of nonendocrine tumor, ulcer, o polyp(s). The argentaffin reaction was positive in three tumors, and the Hellerstr\u00f6m--Hellman argyrophil reaction was positive in four tumors. All tumors reacted positively to the Grimelius argyrophil stain, and 13 were positive with the Sevier--Munger argyrophil stain. Gastrin immunoreactivity was found in eight tumors, and substance-P immunoreactivity in seven tumors. No enteroglucagon, adrenal cortex hormone, or pancreatic polypeptide was observed in any of the tumors. Three patients with Sevier--Munger-positive gastric tumors had concurrent pernicious anemia, and 2 patients with gastrin-immunoreactive tumors had acute or chronic gastroduodenal ulceration. The results indicate that the gastroduodenal endocrine tumor as a rule gives no endocrine symptoms and that the tumor type is an unexpected finding at operation. The tumors may contain gastrin, substance P, somatostatin, and serotonin and tend to be multihormonal."}
{"id": "PMID:224708", "title": "Selective mitochondrial degeneration in renal tubules following hyperbaric oxygen exposure.", "content": "To study the ultrastructural effects of hyperoxia on the kidney, young adult Sprague Dawley rats were exposed to 3 atmospheres absolute (ATAs) of pure oxygen for 5 hours and were killed in a time sequence varying from immediately to 30 days after exposure. Their renal cortices were processed for electron microscopy. Selective mitochondrial changes were observed within sublethally and transiently altered proximal tubular epithelial cells. The most consistent finding was the accumulation of 0.08 mu to 0.5 mu round to ovoid homogeneous matrical inclusions which frequently formed larger confluent amorphous masses. The inclusions stained intensely with lead and uranium but appeared homogeneously electron-lucent in unstained sections. Energy-dispersive x-ray analysis revealed that they did not contain calcium or phosphorus. The inclusions were different from the innately electron-opaque flocculent densities commonly found in pathologically altered mitochondria. Since the mitochondria containing them were removed by autophagocytosis, it is suggested that the inclusions were associated with selective mitochondrial degeneration induced by hyperoxia. No glomerular lesions were found.", "contents": "Selective mitochondrial degeneration in renal tubules following hyperbaric oxygen exposure. To study the ultrastructural effects of hyperoxia on the kidney, young adult Sprague Dawley rats were exposed to 3 atmospheres absolute (ATAs) of pure oxygen for 5 hours and were killed in a time sequence varying from immediately to 30 days after exposure. Their renal cortices were processed for electron microscopy. Selective mitochondrial changes were observed within sublethally and transiently altered proximal tubular epithelial cells. The most consistent finding was the accumulation of 0.08 mu to 0.5 mu round to ovoid homogeneous matrical inclusions which frequently formed larger confluent amorphous masses. The inclusions stained intensely with lead and uranium but appeared homogeneously electron-lucent in unstained sections. Energy-dispersive x-ray analysis revealed that they did not contain calcium or phosphorus. The inclusions were different from the innately electron-opaque flocculent densities commonly found in pathologically altered mitochondria. Since the mitochondria containing them were removed by autophagocytosis, it is suggested that the inclusions were associated with selective mitochondrial degeneration induced by hyperoxia. No glomerular lesions were found."}
{"id": "PMID:224709", "title": "Na+,K+-ATPase enzyme units in lean and obese (ob/ob) thyroxine-injected mice.", "content": "The possible involvement of Na+,K+-ATPase in the etiology of obesity in the obese (ob/ob) mouse was explored. The number of Na+,K+-ATPase enzyme units in skeletal muscle, liver, and kidneys from 4- and 8-wk-old obese and lean mice was estimated from saturable [3H]ouabain binding to particulate fractions. Neither phenotype nor age altered the Kd value for ouabain binding in these three tissue preparations. The total number of [3H]ouabain binding sites in hindlimb muscles was 35--55% lower in 4- and 8-wk-old obese mice than in their lean counterparts. However, the total number of [3H]ouabain binding sites in liver and kidneys of obese mice was similar to values observed in their lean counterparts. Because it has been suggested that ob/ob mice are hypothyroid, we investigated the response of Na+,K+-ATPase in these mice to thyroid hormone treatment (approximately 5 microgram thyroxine/day for 2 wk). The number of [3H]ouabain binding sites in the three tissues increased in both obese and lean mice injected with this relatively large dose of thyroxine, but the obese mice were 2--3 times more responsive than lean mice.", "contents": "Na+,K+-ATPase enzyme units in lean and obese (ob/ob) thyroxine-injected mice. The possible involvement of Na+,K+-ATPase in the etiology of obesity in the obese (ob/ob) mouse was explored. The number of Na+,K+-ATPase enzyme units in skeletal muscle, liver, and kidneys from 4- and 8-wk-old obese and lean mice was estimated from saturable [3H]ouabain binding to particulate fractions. Neither phenotype nor age altered the Kd value for ouabain binding in these three tissue preparations. The total number of [3H]ouabain binding sites in hindlimb muscles was 35--55% lower in 4- and 8-wk-old obese mice than in their lean counterparts. However, the total number of [3H]ouabain binding sites in liver and kidneys of obese mice was similar to values observed in their lean counterparts. Because it has been suggested that ob/ob mice are hypothyroid, we investigated the response of Na+,K+-ATPase in these mice to thyroid hormone treatment (approximately 5 microgram thyroxine/day for 2 wk). The number of [3H]ouabain binding sites in the three tissues increased in both obese and lean mice injected with this relatively large dose of thyroxine, but the obese mice were 2--3 times more responsive than lean mice."}
{"id": "PMID:224710", "title": "Mucosal gastrin receptor. I. Assay standardization and fulfillment of receptor criteria.", "content": "Using iodinated gastrin with demonstrable biological activity, this study has shown that optimal specific gastrin binding occurs in rat gastric mucosal 270--30,000 g membrane preparations after an incubation period of 30 min at 30 degrees C (pH 7.4) with a protein concentration of 150--200 micrograms per assay tube. The gastrin binding was shown to be saturable with an equilibrium Ka of approximately 0.25 X 10(10) M-1 and an equilibrium Kd of approximately 4 X 10(10) M. The binding capacity was approximately 4 fmol/mg protein. Specific gastrin binding was shown to be present in the oxyntic gland and duodenal mucosa and to be absent from the antral mucosa, liver, spleen, and kidney. In order to decrease the specific binding of gastrin by 50% the competitors in order of potency are 15-Leu G-17 greater than cholecystokinin greater than caerulein greater than pentagastrin; secretin did not display a response similar to the other four competitors tested, indicating that its inhibition may be non-competitive. Fasting decreased the binding capacity of the gastrin receptor and refeeding brought the receptor levels back to control range; this result parallels the decrease seen in serum gastrin after fasting and the return to normal levels with refeeding. This suggests that rat gastric mucosal gastrin receptors may exhibit autoregulation. This study is the first to meet all the criteria for establishing the existence of a mucosal gastrin receptor.", "contents": "Mucosal gastrin receptor. I. Assay standardization and fulfillment of receptor criteria. Using iodinated gastrin with demonstrable biological activity, this study has shown that optimal specific gastrin binding occurs in rat gastric mucosal 270--30,000 g membrane preparations after an incubation period of 30 min at 30 degrees C (pH 7.4) with a protein concentration of 150--200 micrograms per assay tube. The gastrin binding was shown to be saturable with an equilibrium Ka of approximately 0.25 X 10(10) M-1 and an equilibrium Kd of approximately 4 X 10(10) M. The binding capacity was approximately 4 fmol/mg protein. Specific gastrin binding was shown to be present in the oxyntic gland and duodenal mucosa and to be absent from the antral mucosa, liver, spleen, and kidney. In order to decrease the specific binding of gastrin by 50% the competitors in order of potency are 15-Leu G-17 greater than cholecystokinin greater than caerulein greater than pentagastrin; secretin did not display a response similar to the other four competitors tested, indicating that its inhibition may be non-competitive. Fasting decreased the binding capacity of the gastrin receptor and refeeding brought the receptor levels back to control range; this result parallels the decrease seen in serum gastrin after fasting and the return to normal levels with refeeding. This suggests that rat gastric mucosal gastrin receptors may exhibit autoregulation. This study is the first to meet all the criteria for establishing the existence of a mucosal gastrin receptor."}
{"id": "PMID:224711", "title": "Mucosal gastrin receptor. II. Physical characteristics of binding.", "content": "Gastrin binding to rat gastric mucosal membrane preparations revealed a linear Scatchard plot, suggesting the existence of a single class of binding sites. Further studies revealed the absence of a positive cooperative effect. Because the system appeared to satisfy the conditions for Michaelis-Menten type kinetics, the determination of a Kd of approximately 3.6 X 10(-10) M was justified. These studies also demonstrated the efficacy of the specific activity of our iodinated gastrin. Trypsin treatment abolished specific binding of gastrin to the membrane preparation, indicating the protein nature of the receptor. The importance of maintaining extremely low temperatures during the incubation and wash period is demonstrated by the decrease in both the rate and the amount of dissociation at 0 degrees C compared with 30 degrees C.", "contents": "Mucosal gastrin receptor. II. Physical characteristics of binding. Gastrin binding to rat gastric mucosal membrane preparations revealed a linear Scatchard plot, suggesting the existence of a single class of binding sites. Further studies revealed the absence of a positive cooperative effect. Because the system appeared to satisfy the conditions for Michaelis-Menten type kinetics, the determination of a Kd of approximately 3.6 X 10(-10) M was justified. These studies also demonstrated the efficacy of the specific activity of our iodinated gastrin. Trypsin treatment abolished specific binding of gastrin to the membrane preparation, indicating the protein nature of the receptor. The importance of maintaining extremely low temperatures during the incubation and wash period is demonstrated by the decrease in both the rate and the amount of dissociation at 0 degrees C compared with 30 degrees C."}
{"id": "PMID:224712", "title": "Dissociation between plasma, urine, and renal papillary cyclic AMP content following vasopressin and DDAVP.", "content": "The effects of in vivo physiologic doses of vasopressin and 1-deamino-8-D-arginine vasopressin (DDAVP) on the cyclic AMP content of plasma, urine, and renal papillary tissue were determined in the ADH-deficient Brattleboro rat. During clearance studies, plasma cyclic AMP concentrations and both total and nephrogenous urinary cyclic AMP excretion in vasopressin- and DDAVP-treated rats were similar to the values in time-matched controls. In contrast, in situ renal papillary cyclic AMP content was higher (P less than 0.001) in both vasopressin- (35.7 +/- 3.6 pmol/mg protein) and DDAVP- (29.7 +/- 2.2 pmol/mg protein) treated rats compared to controls (15.1 +/- 1.3 pmol/mg protein). Endogenous stimulation of vasopressin by dehydration in normal rats increased both papillary cyclic AMP content (27.1 +/- 2.7 pmol/mg protein) and urine osmolality, whereas no change in papillary cyclic AMP was observed following dehydration in Brattleboro rats (13.6 +/- 0.8 pmol/mg protein) despite an increase in urine osmolality. The results demonstrate that changes in cyclic AMP following in vivo vasopressin are best demonstrated by measurement of in situ cyclic AMP content of the renal papilla, whereas total urinary cyclic AMP and nephrogenous cyclic AMP are not useful indices of tubular sensitivity to this hormone.", "contents": "Dissociation between plasma, urine, and renal papillary cyclic AMP content following vasopressin and DDAVP. The effects of in vivo physiologic doses of vasopressin and 1-deamino-8-D-arginine vasopressin (DDAVP) on the cyclic AMP content of plasma, urine, and renal papillary tissue were determined in the ADH-deficient Brattleboro rat. During clearance studies, plasma cyclic AMP concentrations and both total and nephrogenous urinary cyclic AMP excretion in vasopressin- and DDAVP-treated rats were similar to the values in time-matched controls. In contrast, in situ renal papillary cyclic AMP content was higher (P less than 0.001) in both vasopressin- (35.7 +/- 3.6 pmol/mg protein) and DDAVP- (29.7 +/- 2.2 pmol/mg protein) treated rats compared to controls (15.1 +/- 1.3 pmol/mg protein). Endogenous stimulation of vasopressin by dehydration in normal rats increased both papillary cyclic AMP content (27.1 +/- 2.7 pmol/mg protein) and urine osmolality, whereas no change in papillary cyclic AMP was observed following dehydration in Brattleboro rats (13.6 +/- 0.8 pmol/mg protein) despite an increase in urine osmolality. The results demonstrate that changes in cyclic AMP following in vivo vasopressin are best demonstrated by measurement of in situ cyclic AMP content of the renal papilla, whereas total urinary cyclic AMP and nephrogenous cyclic AMP are not useful indices of tubular sensitivity to this hormone."}
{"id": "PMID:224713", "title": "Effect of fasting on tubular phosphorus reabsorption.", "content": "In the thyroparathyroidectomized (TPTX) rat, fasting increased urinary phosphorus excretion by decreasing the tubular reabsorption of P1 (TRP) and resulted in hypophosphatemia. The administration of either sucrose or NaHCO3 prevented the metabolic acidosis associated with fasting and decreased the phosphaturia, indicating that the phosphaturia in fasting is in part due to metabolic acidosis. In rats on partial reduction of P1 intake selectively, the phosphaturic response to parathyroid hormone (PTH) was completely suppressed. On the other hand, the fasting rat partially retained the phosphaturic response to PTH, although dietary P1 intake was totally absent. These findings suggest that the renal P1 wasting in fasting may take place by dual mechanisms: a) the PTH-independent decrease in TRP, and b) an inability to totally suppress the response to PTH. Cyclic AMP generation in response to PTH, determined both in vivo and in vitro, was not measurably altered in fasting. However, the phosphaturic response to cyclic AMP was decreased in fasting, suggesting that the mechanism of partial resistance to PTH is probably not at but after cyclic AMP generation.", "contents": "Effect of fasting on tubular phosphorus reabsorption. In the thyroparathyroidectomized (TPTX) rat, fasting increased urinary phosphorus excretion by decreasing the tubular reabsorption of P1 (TRP) and resulted in hypophosphatemia. The administration of either sucrose or NaHCO3 prevented the metabolic acidosis associated with fasting and decreased the phosphaturia, indicating that the phosphaturia in fasting is in part due to metabolic acidosis. In rats on partial reduction of P1 intake selectively, the phosphaturic response to parathyroid hormone (PTH) was completely suppressed. On the other hand, the fasting rat partially retained the phosphaturic response to PTH, although dietary P1 intake was totally absent. These findings suggest that the renal P1 wasting in fasting may take place by dual mechanisms: a) the PTH-independent decrease in TRP, and b) an inability to totally suppress the response to PTH. Cyclic AMP generation in response to PTH, determined both in vivo and in vitro, was not measurably altered in fasting. However, the phosphaturic response to cyclic AMP was decreased in fasting, suggesting that the mechanism of partial resistance to PTH is probably not at but after cyclic AMP generation."}
{"id": "PMID:224714", "title": "Effects of repetitive bursts of vagal activity on atrioventricular junctional rate in dogs.", "content": "A stable atrioventricular (AV) junctional rhythm was produced in open-chest dogs by injecting pentobarbital into the sinus node artery. When the cervical vagus nerves were stimulated repetitively, the junctional pacemaker cells tended to become synchronized with the vagal activity. During such synchronization, the junctional rate varied directly rather than inversely with the frequency of vagal stimulation. The magnitude of the chronotropic response depended on the timing of the vagal stimuli within the cardiac cycle. In 9 dogs, when the mean heart periods were plotted as a function of the R-st intervals (i.e., the time from the beginning of ventricular depolarization to the beginning of the stimulus burst), the mean heart periods varied from a maximum of 1,815 ms to a minimum of 1,160 ms, depending on the R-st interval. A small change in the R-st interval was capable of evoking a relatively large change in cycle length. Therefore, the impulses from various efferent vagal fibers to the AV junction must arrive almost synchronously, the released acetylcholine must be removed rapidly, and the sensitivity of the pacemaker cells to acetylcholine must change rapidly at some critical time during the cardiac cycle.", "contents": "Effects of repetitive bursts of vagal activity on atrioventricular junctional rate in dogs. A stable atrioventricular (AV) junctional rhythm was produced in open-chest dogs by injecting pentobarbital into the sinus node artery. When the cervical vagus nerves were stimulated repetitively, the junctional pacemaker cells tended to become synchronized with the vagal activity. During such synchronization, the junctional rate varied directly rather than inversely with the frequency of vagal stimulation. The magnitude of the chronotropic response depended on the timing of the vagal stimuli within the cardiac cycle. In 9 dogs, when the mean heart periods were plotted as a function of the R-st intervals (i.e., the time from the beginning of ventricular depolarization to the beginning of the stimulus burst), the mean heart periods varied from a maximum of 1,815 ms to a minimum of 1,160 ms, depending on the R-st interval. A small change in the R-st interval was capable of evoking a relatively large change in cycle length. Therefore, the impulses from various efferent vagal fibers to the AV junction must arrive almost synchronously, the released acetylcholine must be removed rapidly, and the sensitivity of the pacemaker cells to acetylcholine must change rapidly at some critical time during the cardiac cycle."}
{"id": "PMID:224715", "title": "Presynaptic inhibition of canine renal adrenergic nerves by acetylcholine in vivo.", "content": "Experiments were performed in anesthetized dogs to determine whether previously reported in vitro inhibition of sympathetic neurotransmitter release by acetylcholine could be demonstrated in the renal vasculature of the intact animal. Vasoconstrictor responses to renal sympathetic nerve stimulation at varying frequencies were compared to intra-arterial injections of norepinephrine before and during intra-arterial infusions of acetylcholine, 2.5--80 micrograms/min. The vasoconstrictor responses to nerve stimulation were inhibited to a greater extent than were responses to norepinephrine during infusions of acetylcholine. The inhibitory effects of acetylcholine on nerve stimulation were dose and frequency dependent. The inhibition was blocked by atropine but not altered by physostigmine. Changes in renal blood flow per se did not contribute to the inhibitory effect of acetylcholine, since another vasodilator agent, sodium acetate, did not affect the nerve stimulation-norepinephrine vasocontriction relationship. Thus, acetylcholine produced inhibition of in vivo renal sympathetic vasoconstrictor responses, and the receptor involved appears to be muscarinic.", "contents": "Presynaptic inhibition of canine renal adrenergic nerves by acetylcholine in vivo. Experiments were performed in anesthetized dogs to determine whether previously reported in vitro inhibition of sympathetic neurotransmitter release by acetylcholine could be demonstrated in the renal vasculature of the intact animal. Vasoconstrictor responses to renal sympathetic nerve stimulation at varying frequencies were compared to intra-arterial injections of norepinephrine before and during intra-arterial infusions of acetylcholine, 2.5--80 micrograms/min. The vasoconstrictor responses to nerve stimulation were inhibited to a greater extent than were responses to norepinephrine during infusions of acetylcholine. The inhibitory effects of acetylcholine on nerve stimulation were dose and frequency dependent. The inhibition was blocked by atropine but not altered by physostigmine. Changes in renal blood flow per se did not contribute to the inhibitory effect of acetylcholine, since another vasodilator agent, sodium acetate, did not affect the nerve stimulation-norepinephrine vasocontriction relationship. Thus, acetylcholine produced inhibition of in vivo renal sympathetic vasoconstrictor responses, and the receptor involved appears to be muscarinic."}
{"id": "PMID:224716", "title": "Ascending spinal pathways for the somatosympathetic A and C reflexes.", "content": "Sympathetic unit nerve activity was recorded from the cervical sympathetic trunk of anesthetized, vagotomized, and carotid sinus-denervated cats. Single pulses or short trains of pulses with suprathreshold intensity for afferent C fibers were applied to the common peroneal nerve to elicit somatosympathetic A or simultaneous A and C reflexes, respectively. Bilateral lesions of an ascending spinal pathway in the dorsolateral sulcus area (DLS) of the T12 spinal cord eliminated the sympathetic C reflex. The remaining somatosympathetic A reflex was abolished by the subsequent lesion of an ascending spinal pathway in the dorsolateral funiculus (DLF) bilaterally. The duration of the silent period was found to be mainly influenced by an ascending spinal pathway in the DLF. It was concluded that excitation of afferent A fibers activates ascending pathways mainly in the DLF and a smaller contribution in the DLS of the spinal cord. This produces a small reflex excitation (A reflex) followed by a long silent period in the sympathetic nerves resulting in a net decrease of total sympathetic nerve activity. On the other hand, excitation of afferent C fibers activates the ascending spinal pathway in the DLS. This produces a reflex excitation (C reflex) which exceeds the decreased activity due to the silent period resulting in a net increase of total sympathetic nerve activity.", "contents": "Ascending spinal pathways for the somatosympathetic A and C reflexes. Sympathetic unit nerve activity was recorded from the cervical sympathetic trunk of anesthetized, vagotomized, and carotid sinus-denervated cats. Single pulses or short trains of pulses with suprathreshold intensity for afferent C fibers were applied to the common peroneal nerve to elicit somatosympathetic A or simultaneous A and C reflexes, respectively. Bilateral lesions of an ascending spinal pathway in the dorsolateral sulcus area (DLS) of the T12 spinal cord eliminated the sympathetic C reflex. The remaining somatosympathetic A reflex was abolished by the subsequent lesion of an ascending spinal pathway in the dorsolateral funiculus (DLF) bilaterally. The duration of the silent period was found to be mainly influenced by an ascending spinal pathway in the DLF. It was concluded that excitation of afferent A fibers activates ascending pathways mainly in the DLF and a smaller contribution in the DLS of the spinal cord. This produces a small reflex excitation (A reflex) followed by a long silent period in the sympathetic nerves resulting in a net decrease of total sympathetic nerve activity. On the other hand, excitation of afferent C fibers activates the ascending spinal pathway in the DLS. This produces a reflex excitation (C reflex) which exceeds the decreased activity due to the silent period resulting in a net increase of total sympathetic nerve activity."}
{"id": "PMID:224717", "title": "Liver glycogenolysis during exercise without a significant increase in cAMP.", "content": "Liver glycogenolysis may be controlled by glucagon or catecholamine-induced changes in cAMP or by cAMP-independent mechanisms. The purpose of these experiments was to determine whether an increase in liver cAMP occurs during exercise at a time when the rate of liver glycogenolysis is greatly accelerated. Rats were taught to run on a treadmill 10 min/day for 6 wk. They were then run continuously for periods of time ranging from 0 to 120 min at 0.8 mph up a 15% grade. Liver glycogen was depleted by the end of 90 min in fed animals and by 20 min in overnight-fasted animals. Liver cAMP was not significantly increased in fed animals during the first 60 min of exercise. The major increase in liver cAMP occurred after liver glycogen was depleted, at which time the rat must rely entirely on gluconeogenesis for maintenance of blood glucose. This increase in cAMP corresponded to large increases in plasma glucagon and catecholamines. We conclude that liver glycogenolysis in the rat can occur during exercise independently from significant detectable increases in cAMP concentrations.", "contents": "Liver glycogenolysis during exercise without a significant increase in cAMP. Liver glycogenolysis may be controlled by glucagon or catecholamine-induced changes in cAMP or by cAMP-independent mechanisms. The purpose of these experiments was to determine whether an increase in liver cAMP occurs during exercise at a time when the rate of liver glycogenolysis is greatly accelerated. Rats were taught to run on a treadmill 10 min/day for 6 wk. They were then run continuously for periods of time ranging from 0 to 120 min at 0.8 mph up a 15% grade. Liver glycogen was depleted by the end of 90 min in fed animals and by 20 min in overnight-fasted animals. Liver cAMP was not significantly increased in fed animals during the first 60 min of exercise. The major increase in liver cAMP occurred after liver glycogen was depleted, at which time the rat must rely entirely on gluconeogenesis for maintenance of blood glucose. This increase in cAMP corresponded to large increases in plasma glucagon and catecholamines. We conclude that liver glycogenolysis in the rat can occur during exercise independently from significant detectable increases in cAMP concentrations."}
{"id": "PMID:224718", "title": "Computer simulation of metabolism in pyruvate-perfused rat heart. II. Krebs cycle.", "content": "A realistic metabolic model of the tricarboxylic acid cycle in the perfused rat heart was constructed to help explain the sequence of biochemical events regulating the metabolism of exogenous pyruvate following a large increase in work load. The unchelated Mg2+ level was the most important controlling factor. The resulting mixture of chelated and unchelated nucleotides and tribasic acids effected coordinated control of citrate synthase, aconitase, isocitrate dehydrogenase, succinyl CoA synthetase, fumarase, and nucleoside diphosphokinase, because Mg2+-chelates are generally substrates whereas unchelated species are inhibitors. Succinate dehydrogenase is largely controlled by the ubiquinone redox potential. The fluxes through alpha-ketoglutarate and malate dehydrogenases are largely dependent on thepyridine nucleotide redox potential, but the succinyl CoA-to-CoASH ratio strongly affects the former enzyme as well. The model predicts an accumulation of succinate during the transition to higher work output.", "contents": "Computer simulation of metabolism in pyruvate-perfused rat heart. II. Krebs cycle. A realistic metabolic model of the tricarboxylic acid cycle in the perfused rat heart was constructed to help explain the sequence of biochemical events regulating the metabolism of exogenous pyruvate following a large increase in work load. The unchelated Mg2+ level was the most important controlling factor. The resulting mixture of chelated and unchelated nucleotides and tribasic acids effected coordinated control of citrate synthase, aconitase, isocitrate dehydrogenase, succinyl CoA synthetase, fumarase, and nucleoside diphosphokinase, because Mg2+-chelates are generally substrates whereas unchelated species are inhibitors. Succinate dehydrogenase is largely controlled by the ubiquinone redox potential. The fluxes through alpha-ketoglutarate and malate dehydrogenases are largely dependent on thepyridine nucleotide redox potential, but the succinyl CoA-to-CoASH ratio strongly affects the former enzyme as well. The model predicts an accumulation of succinate during the transition to higher work output."}
{"id": "PMID:224719", "title": "Computer simulation of metabolism in pyruvate-perfused rat heart. V. Physiological implications.", "content": "The results of a simulation of metabolism in the pyruvate-perfused rat heart subjected to a sudden increase in work load are interpreted to provide a coherent explanation for the observed physiology. Respiration is most closely correlated with the mitochondrial phosphate potential, calculated from the MgATP and MgADP levels. No correlation between respiration and the pH gradient across the mitochondrial membrane was found. The transient falls in pH in the cytosol and perhaps the mitochondria are due largely to carbonic and lactic acidosis and appear to be only weakly coupled. The heart maintains a high ATP level during the transition to increased work by utilizing its energy reserves in order of decreasing availability in response to physiological signals mediated by Mg2+, Ca2+, and cAMP.", "contents": "Computer simulation of metabolism in pyruvate-perfused rat heart. V. Physiological implications. The results of a simulation of metabolism in the pyruvate-perfused rat heart subjected to a sudden increase in work load are interpreted to provide a coherent explanation for the observed physiology. Respiration is most closely correlated with the mitochondrial phosphate potential, calculated from the MgATP and MgADP levels. No correlation between respiration and the pH gradient across the mitochondrial membrane was found. The transient falls in pH in the cytosol and perhaps the mitochondria are due largely to carbonic and lactic acidosis and appear to be only weakly coupled. The heart maintains a high ATP level during the transition to increased work by utilizing its energy reserves in order of decreasing availability in response to physiological signals mediated by Mg2+, Ca2+, and cAMP."}
{"id": "PMID:224721", "title": "Results of hepatic lobectomy for primary epithelial cancer in 31 adults.", "content": "Hepatic lobectomy for primary epithelial cancer was performed in 31 adults from 1964 through 1977 in the surgical departments of six Scandinavian hospitals. Twenty-three patients were discharged and had a 2 year survival rate of 62 per cent and a 5 year survival rate of 16 per cent. Alternatives to surgery have not yet emerged. Further progress requires centralization.", "contents": "Results of hepatic lobectomy for primary epithelial cancer in 31 adults. Hepatic lobectomy for primary epithelial cancer was performed in 31 adults from 1964 through 1977 in the surgical departments of six Scandinavian hospitals. Twenty-three patients were discharged and had a 2 year survival rate of 62 per cent and a 5 year survival rate of 16 per cent. Alternatives to surgery have not yet emerged. Further progress requires centralization."}
{"id": "PMID:224731", "title": "[The fine structure of the exocrine pancreas of the mink (author's transl)].", "content": "The pancreas of female mink has been investigated by transmission electron microscopic means. The following results can be summarized: The pancreas of the mink is built up by the well known gland lobules as found in many other species; each lobule contains branched ducts with acini. The acinar cells are characteristically packed with granular endoplasmic reticulum, large Golgi apparatuses, and zymogen granules. Particularly interesting are large vacuoles, which seem to emerge directly from the endoplasmic reticular cysternae. The centroacinar cells form relatively extended protrusions or pseudopodia, which frequently penetrate into the intercellular spaces between neighbouring acinar cells. The peripheral isthmic parts of the ducts are covered by an isoprismatic epithelium. The adventitial tissue of the intralobular ducts contain mucous glands. Within the loose connective tissue between the exocrine cells, blood vessels as well as numerous nerves can be found. These results are compared to earlier reports on the same subject, and are also discussed together with available data from the literature.", "contents": "[The fine structure of the exocrine pancreas of the mink (author's transl)]. The pancreas of female mink has been investigated by transmission electron microscopic means. The following results can be summarized: The pancreas of the mink is built up by the well known gland lobules as found in many other species; each lobule contains branched ducts with acini. The acinar cells are characteristically packed with granular endoplasmic reticulum, large Golgi apparatuses, and zymogen granules. Particularly interesting are large vacuoles, which seem to emerge directly from the endoplasmic reticular cysternae. The centroacinar cells form relatively extended protrusions or pseudopodia, which frequently penetrate into the intercellular spaces between neighbouring acinar cells. The peripheral isthmic parts of the ducts are covered by an isoprismatic epithelium. The adventitial tissue of the intralobular ducts contain mucous glands. Within the loose connective tissue between the exocrine cells, blood vessels as well as numerous nerves can be found. These results are compared to earlier reports on the same subject, and are also discussed together with available data from the literature."}
{"id": "PMID:224732", "title": "Morphology of osteoclasts in resorbing fetal rat bone explants: effects of PTH and AIF in vitro.", "content": "Osteoclastic bone resorption was studied using 45Ca-labeled fetal rat bones cultured in the presence of parathyroid hormone (PTH) and an anti-invasion factor (AIF) derived from bovine hyaline cartilage which is enriched in a collagenase inhibitor. The specific morphological expressions of osteoclasts cultured in PTH and AIF were observed in both light and electron microscopy and analyzed cytometrically. Stimulation of bone resorption with PTH revealed significant increases in the numbers and activity of osteoclasts, whereas bones cultured in the presence of AIF showed significant decreases in numbers of osteoclasts and altered cell features including the loss of osteoclast contact with bone surfaces. These structural modifications were evaluated with 45Ca release data derived from matched-pair explants of fetal rat bones, revealing the existence of a relationship between resorptive states of the cultured bones and morphological expressions of osteoclastic activity.", "contents": "Morphology of osteoclasts in resorbing fetal rat bone explants: effects of PTH and AIF in vitro. Osteoclastic bone resorption was studied using 45Ca-labeled fetal rat bones cultured in the presence of parathyroid hormone (PTH) and an anti-invasion factor (AIF) derived from bovine hyaline cartilage which is enriched in a collagenase inhibitor. The specific morphological expressions of osteoclasts cultured in PTH and AIF were observed in both light and electron microscopy and analyzed cytometrically. Stimulation of bone resorption with PTH revealed significant increases in the numbers and activity of osteoclasts, whereas bones cultured in the presence of AIF showed significant decreases in numbers of osteoclasts and altered cell features including the loss of osteoclast contact with bone surfaces. These structural modifications were evaluated with 45Ca release data derived from matched-pair explants of fetal rat bones, revealing the existence of a relationship between resorptive states of the cultured bones and morphological expressions of osteoclastic activity."}
{"id": "PMID:224733", "title": "Lipoprotein particles in the jejunal mucosa of postnatal developing rats.", "content": "The jejunal mucosa of neonatal rats contains lipid particles of the same size, electron density and intracellular and extracellular distribution as particles identified by others in adult jejunum as lipoprotein particles. As in fetal jejunum obtained during the last three days of gestation, the jejunal mucosa of unsuckled newborn rats contains exclusively lipoprotein particles the size of very low density lipoproteins (VLDL). Within one day after initiation of suckling, there is in the mucosa a spectrum of lipoprotein particles ranging widely in size from those of VLDL particles to those of chylomicrons. These particles are seen in the endoplasmic reticulum and Golgi material of absorptive cells and within interepithelial cell spaces, the extracellular spaces of the lamina propria and lymphatic lacteals. VLDL-sized and chylomicron-sized particles are also seen, although in decreasing number, in the jejunal mucosa of 18-day-old suckling rats. However, in rats of comparable age, fasted for 48 or 72 hours, only VLDL-sized particles are seen in the jejunal mucosa. Ligation and transection of bile duct followed by fasting in rats of this age results in a marked decrease in the number of lipoprotein particles in absorptive cells. The results indicate that endogenous lipid contributes to the formation of VLDL particles whereas dietary triglycerides are needed for formation of chylomicrons.", "contents": "Lipoprotein particles in the jejunal mucosa of postnatal developing rats. The jejunal mucosa of neonatal rats contains lipid particles of the same size, electron density and intracellular and extracellular distribution as particles identified by others in adult jejunum as lipoprotein particles. As in fetal jejunum obtained during the last three days of gestation, the jejunal mucosa of unsuckled newborn rats contains exclusively lipoprotein particles the size of very low density lipoproteins (VLDL). Within one day after initiation of suckling, there is in the mucosa a spectrum of lipoprotein particles ranging widely in size from those of VLDL particles to those of chylomicrons. These particles are seen in the endoplasmic reticulum and Golgi material of absorptive cells and within interepithelial cell spaces, the extracellular spaces of the lamina propria and lymphatic lacteals. VLDL-sized and chylomicron-sized particles are also seen, although in decreasing number, in the jejunal mucosa of 18-day-old suckling rats. However, in rats of comparable age, fasted for 48 or 72 hours, only VLDL-sized particles are seen in the jejunal mucosa. Ligation and transection of bile duct followed by fasting in rats of this age results in a marked decrease in the number of lipoprotein particles in absorptive cells. The results indicate that endogenous lipid contributes to the formation of VLDL particles whereas dietary triglycerides are needed for formation of chylomicrons."}
{"id": "PMID:224735", "title": "Bovine trypanosomiasis: effect on the immune response of the infected host.", "content": "Yearling cattle were inoculated with a recently isolated field strain of Trypanosoma congolense. Dinitrophenylated ovalbumin, a bacteriophage, or bovine parainfluenza-3 virus injected into the cattle during the first 5 weeks of infection resulted in peak serum antibody titers lower but not much lower than those produced by noninfected cattle. Primary and secondary antibody responses of inoculated cattle required more time to reach peak titers. Peripheral blood lymphocyte concentrations decreased to 42% of preinfection base-line value 1 1/2 weeks after the onset of T congolense infection and thereafter plateaued at less than 75% of base-line value. Lymphocyte cultures prepared from infected and noninfected cattle gave no marked differences in [(3)H]thymidine uptake after stimulation with phytohemagglutinin or pokeweed mitogen. Differences in lymphpocyte responsiveness were not noticed in one-way mixed lymphocyte culture reactions, using mitomycin C-treated lymphocytes from noninfected cattle as stimulator cells.", "contents": "Bovine trypanosomiasis: effect on the immune response of the infected host. Yearling cattle were inoculated with a recently isolated field strain of Trypanosoma congolense. Dinitrophenylated ovalbumin, a bacteriophage, or bovine parainfluenza-3 virus injected into the cattle during the first 5 weeks of infection resulted in peak serum antibody titers lower but not much lower than those produced by noninfected cattle. Primary and secondary antibody responses of inoculated cattle required more time to reach peak titers. Peripheral blood lymphocyte concentrations decreased to 42% of preinfection base-line value 1 1/2 weeks after the onset of T congolense infection and thereafter plateaued at less than 75% of base-line value. Lymphocyte cultures prepared from infected and noninfected cattle gave no marked differences in [(3)H]thymidine uptake after stimulation with phytohemagglutinin or pokeweed mitogen. Differences in lymphpocyte responsiveness were not noticed in one-way mixed lymphocyte culture reactions, using mitomycin C-treated lymphocytes from noninfected cattle as stimulator cells."}
{"id": "PMID:224736", "title": "Concurrent porcine rotaviral and transmissible gastroenteritis viral infections in a three-day-old conventional pig.", "content": "A 3-day-old suckling pig with diarrhea was necropsied, and immunofluorescent microscopic examination of the small intestinal mucosa, together with immune electron microscopic examination of the large intestinal contents, provided a presumptive diagnosis of a concurrent infection with transmissible gastroenteritis (TGE) virus and porcine rotavirus. Immunofluorescent microscopic, immune electron microscopic, and serologic data obtained from gnotobiotic pigs experimentally inoculated with the large intestinal contents of the suckling pig confirmed this diagnosis. Two gnotobiotic pigs, convalescent from previous TGE viral infections, became infected with porcine rotavirus only. However, another gnotobiotic pig, convalescent from a previous porcine rotaviral infection, became infected with TGE virus only, following inoculation with the large intestinal contents of the suckling pig.", "contents": "Concurrent porcine rotaviral and transmissible gastroenteritis viral infections in a three-day-old conventional pig. A 3-day-old suckling pig with diarrhea was necropsied, and immunofluorescent microscopic examination of the small intestinal mucosa, together with immune electron microscopic examination of the large intestinal contents, provided a presumptive diagnosis of a concurrent infection with transmissible gastroenteritis (TGE) virus and porcine rotavirus. Immunofluorescent microscopic, immune electron microscopic, and serologic data obtained from gnotobiotic pigs experimentally inoculated with the large intestinal contents of the suckling pig confirmed this diagnosis. Two gnotobiotic pigs, convalescent from previous TGE viral infections, became infected with porcine rotavirus only. However, another gnotobiotic pig, convalescent from a previous porcine rotaviral infection, became infected with TGE virus only, following inoculation with the large intestinal contents of the suckling pig."}
{"id": "PMID:224737", "title": "Adrenal gland function in the horse: effects of cosyntropin (synthetic) and corticotropin (natural) stimulation.", "content": "The plasma concentration of hydrocortisone was determined in mares given either cosyntropin (100 IU, given IV) or corticotropin (200 IU, given IM). Plasma hydrocortisone concentrations of the mares treated with cosyntropin increased by 46%, 57% and 80% at 30, 60, and 120 minutes, respectively, when compared with base-line values; these values returned to base line at 240 minutes. In mares treated with corticotropin, mean plasma hydrocortisone concentrations increased by 42%, 143%, 101% and 155% at 30, 60, 120, and 240 minutes, respectively, when compared with base-line values. Differences in total leukocyte count, total eosinophil count, and plasma concentrations of electrolytes (calcium, sodium, magnesium, potassium) of cosyntropin- and corticotropin-treated mares, and these values in control animals were not significant. Results of the present study indicated that the horse responds to small dosages of cosyntropin (IV) in a prompt and reproducible manner as determined by plasma hydrocortisone values. Response to corticotropin was slow and less consistent. Thus, administration of cosyntropin to the horse, according to test results with paired samples collected (before administration and again at 2 hours after injection), was found to be a prompt and meaningful test of adrenal gland function.", "contents": "Adrenal gland function in the horse: effects of cosyntropin (synthetic) and corticotropin (natural) stimulation. The plasma concentration of hydrocortisone was determined in mares given either cosyntropin (100 IU, given IV) or corticotropin (200 IU, given IM). Plasma hydrocortisone concentrations of the mares treated with cosyntropin increased by 46%, 57% and 80% at 30, 60, and 120 minutes, respectively, when compared with base-line values; these values returned to base line at 240 minutes. In mares treated with corticotropin, mean plasma hydrocortisone concentrations increased by 42%, 143%, 101% and 155% at 30, 60, 120, and 240 minutes, respectively, when compared with base-line values. Differences in total leukocyte count, total eosinophil count, and plasma concentrations of electrolytes (calcium, sodium, magnesium, potassium) of cosyntropin- and corticotropin-treated mares, and these values in control animals were not significant. Results of the present study indicated that the horse responds to small dosages of cosyntropin (IV) in a prompt and reproducible manner as determined by plasma hydrocortisone values. Response to corticotropin was slow and less consistent. Thus, administration of cosyntropin to the horse, according to test results with paired samples collected (before administration and again at 2 hours after injection), was found to be a prompt and meaningful test of adrenal gland function."}
{"id": "PMID:224738", "title": "Comparative thermometric coagulation studies of plasmas from normal outbred Swiss Webster mice and persons.", "content": "The functional capabilities of a thermometric clot-timer have been demonstrated in a comparative study of human and mouse plasma coagulation. The influence of some variables on coagulation times of mouse and human plasmas were examined in activated partial thromboplastin time, one-stage prothrombin time, and Russell's viper venom time assays. Mouse plasma coagulation times were generally shorter and more reproducible than those of human plasma. Optimal assay conditions are also described.", "contents": "Comparative thermometric coagulation studies of plasmas from normal outbred Swiss Webster mice and persons. The functional capabilities of a thermometric clot-timer have been demonstrated in a comparative study of human and mouse plasma coagulation. The influence of some variables on coagulation times of mouse and human plasmas were examined in activated partial thromboplastin time, one-stage prothrombin time, and Russell's viper venom time assays. Mouse plasma coagulation times were generally shorter and more reproducible than those of human plasma. Optimal assay conditions are also described."}
{"id": "PMID:224739", "title": "Occurrence of anaerobic bacteria in diseases of the dog and cat.", "content": "A survey for anaerobic bacteria was conducted in 314 clinical specimens from dogs and cats. A total of 187 anaerobic isolates in pure and mixed culture were isolated from 111 of the specimens that contained anaerobic bacteria. Common isolated included Actinomyces (9.1%), Clostridium perfringens (19.3%), other Clostridium spp (11.2%), Peptostreptococcus anaerobius (7.5%), Bacteroides melaninogenicus (13.4%), other Bacteroides spp (17.6%), and Fusobacterium necrophorum (5.3%). Anaerobic bacteria were involved in serious lesions that often were life threatening to the animals. Antibiotic susceptibility data indicated that the lincomycin family, the penicillin family, chloramphenicol, and cephaloridine are preferred drugs for treatment of anaerobic infections. Data from the survey were used in formulation of a table to aid practitioners in clinical diagnosis of disease caused by anaerobes. Clostridium perfringens was isolated in large numbers from five of six dogs with a clinical diagnosis of canine hemorrhagic gastroenteritis and from one cat with hemorrhagic diarrhea. Experimental infections were induced in rats, using caine feces as inoculum. Induced lesions contained aerobic and anaerobic bacteria similar to those bacteria isolated in the clinical survey, indicating that feces may serve as a major source of these bacteria in clinical infections of the dog.", "contents": "Occurrence of anaerobic bacteria in diseases of the dog and cat. A survey for anaerobic bacteria was conducted in 314 clinical specimens from dogs and cats. A total of 187 anaerobic isolates in pure and mixed culture were isolated from 111 of the specimens that contained anaerobic bacteria. Common isolated included Actinomyces (9.1%), Clostridium perfringens (19.3%), other Clostridium spp (11.2%), Peptostreptococcus anaerobius (7.5%), Bacteroides melaninogenicus (13.4%), other Bacteroides spp (17.6%), and Fusobacterium necrophorum (5.3%). Anaerobic bacteria were involved in serious lesions that often were life threatening to the animals. Antibiotic susceptibility data indicated that the lincomycin family, the penicillin family, chloramphenicol, and cephaloridine are preferred drugs for treatment of anaerobic infections. Data from the survey were used in formulation of a table to aid practitioners in clinical diagnosis of disease caused by anaerobes. Clostridium perfringens was isolated in large numbers from five of six dogs with a clinical diagnosis of canine hemorrhagic gastroenteritis and from one cat with hemorrhagic diarrhea. Experimental infections were induced in rats, using caine feces as inoculum. Induced lesions contained aerobic and anaerobic bacteria similar to those bacteria isolated in the clinical survey, indicating that feces may serve as a major source of these bacteria in clinical infections of the dog."}
{"id": "PMID:224742", "title": "Etiology of liver disease in renal-transplant patients.", "content": "The etiology of 72 episodes of liver disease that developed in 62 of 162 renal-transplant recipients was evaluated. Infection with hepatitis B virus was a minor problem, and none of our patients had evidence of infection with hepatitis A. Cytomegalovirus infection was ubiquitous in the population and probably accounted for many episodes of acute liver disease. This agent's role in causing chronic hepatitis is less secure. Infections with other viruses including Epstein-Barr virus, adenovirus, and the herpes viruses were only rarely associated with hepatic disease. Azathioprine was responsible for some episodes of acute cholestasis but could not be incriminated as a direct cause of chronic disease. A cause could be identified for the majority of episodes of acute hepatic dysfunction, but the cause of most of the chronic hepatitis remains undetermined. It is likely that infection with non-A, non-B hepatitis virus accounts for much of this serious, often fatal, complication of renal transplantation.", "contents": "Etiology of liver disease in renal-transplant patients. The etiology of 72 episodes of liver disease that developed in 62 of 162 renal-transplant recipients was evaluated. Infection with hepatitis B virus was a minor problem, and none of our patients had evidence of infection with hepatitis A. Cytomegalovirus infection was ubiquitous in the population and probably accounted for many episodes of acute liver disease. This agent's role in causing chronic hepatitis is less secure. Infections with other viruses including Epstein-Barr virus, adenovirus, and the herpes viruses were only rarely associated with hepatic disease. Azathioprine was responsible for some episodes of acute cholestasis but could not be incriminated as a direct cause of chronic disease. A cause could be identified for the majority of episodes of acute hepatic dysfunction, but the cause of most of the chronic hepatitis remains undetermined. It is likely that infection with non-A, non-B hepatitis virus accounts for much of this serious, often fatal, complication of renal transplantation."}
{"id": "PMID:224746", "title": "[Expression of ts-3 mutant of polyoma virus in mouse cells (author's transl)].", "content": "A thermosensitive mutant (ts-3) of polyoma virus produces T antigen, viral DNA and V antigen in BalbC/3T3 cells only at the permissive temperature (31 degrees C). At the non-permissive temperature (39 degrees C) these cells are unable to complement the viral defect. The pulse technique reveals only transitory cellular DNA induction between 15 and 25 h after infection at 39 degrees C. However, at both temperatures, cytoplasmic penetration is observed, and the viral DNA reaches the nuclei. Similarly, the myoblast cell line PCD2 does not complement the viral defect. In other idfferent types of cells tested (3T6, mouse kidney or secondary embryo cultures), the ts-3 mutant is expressed equally at 31 degrees C and 39 degrees C.", "contents": "[Expression of ts-3 mutant of polyoma virus in mouse cells (author's transl)]. A thermosensitive mutant (ts-3) of polyoma virus produces T antigen, viral DNA and V antigen in BalbC/3T3 cells only at the permissive temperature (31 degrees C). At the non-permissive temperature (39 degrees C) these cells are unable to complement the viral defect. The pulse technique reveals only transitory cellular DNA induction between 15 and 25 h after infection at 39 degrees C. However, at both temperatures, cytoplasmic penetration is observed, and the viral DNA reaches the nuclei. Similarly, the myoblast cell line PCD2 does not complement the viral defect. In other idfferent types of cells tested (3T6, mouse kidney or secondary embryo cultures), the ts-3 mutant is expressed equally at 31 degrees C and 39 degrees C."}
{"id": "PMID:224750", "title": "Phosphodiesters in muscular dystrophies.", "content": "Phosphorus nuclear magnetic resonance studies of various normal and dystrophic muscles have demonstrated differences in phosphodiester contents. Dystrophic chicken pectoralis muscle contains elevated levels of the diester SEP, and Duchenne dystrophic human leg muscle lacks the diester GPC. It is shown that SEP may be characteristic of slow fiber types, indicating imcomplete maturation of the dystrophic pectoralis muscle. The activities of SEP-metabolizing enzymes have been determined in microsomes of pectoralis muscle, kidney, and intestinal mucosa of normal and dystrophic chickens. There was little difference between normal and dystrophic values of SEP phosphodiesterase and SEP synthase in kidney and mucosa. Dystrophic pectoralis muscle microsomes possessed significantly elevated levels of both enzymes. The increase in SEP synthase activity of dystrophic muscle may explain the increase in the SEP level if the phosphodiesterase is regulated in vivo. It is shown that human muscle disease processes may raise, leave unchanged, or lower GPC levels. In certain diseases when GPC is markedly elevated, such as Werdnig-Hoffmann, or depressed, such as Duchenne muscular dystrophy, it may serve as a marker.", "contents": "Phosphodiesters in muscular dystrophies. Phosphorus nuclear magnetic resonance studies of various normal and dystrophic muscles have demonstrated differences in phosphodiester contents. Dystrophic chicken pectoralis muscle contains elevated levels of the diester SEP, and Duchenne dystrophic human leg muscle lacks the diester GPC. It is shown that SEP may be characteristic of slow fiber types, indicating imcomplete maturation of the dystrophic pectoralis muscle. The activities of SEP-metabolizing enzymes have been determined in microsomes of pectoralis muscle, kidney, and intestinal mucosa of normal and dystrophic chickens. There was little difference between normal and dystrophic values of SEP phosphodiesterase and SEP synthase in kidney and mucosa. Dystrophic pectoralis muscle microsomes possessed significantly elevated levels of both enzymes. The increase in SEP synthase activity of dystrophic muscle may explain the increase in the SEP level if the phosphodiesterase is regulated in vivo. It is shown that human muscle disease processes may raise, leave unchanged, or lower GPC levels. In certain diseases when GPC is markedly elevated, such as Werdnig-Hoffmann, or depressed, such as Duchenne muscular dystrophy, it may serve as a marker."}
{"id": "PMID:224751", "title": "Experimental hyperlipidemia in rats.", "content": "Implantation of MtT-F4 tumor, a mammotropic tumor that secretes large quantities of ACTH, GH and prolactin, into male Fisher rats induced the development of hyperlipidemia. Free fatty acid, triglyceride and cholesterol levels in the plasma were significantly increased at 31 days after tumor implantation. Blood glucose and glycerol levels remained normal, while uric acid concentration in the blood was significantly decreased. The concentrations of the serum lipoproteins were significantly increased, while, only small changes in the distribution of the serum lipids and the composition of the lipoproteins were observed. Following stimulation of isolated adipose tissue cells with ACTH, the lipolytic response and the accumulation of cyclic AMP was higher in cells derived from the rats with the tumor, although the accumulation of cyclic GMP was not different from control adipocytes. Further, when the isolated adipose tissue cells were stimulated with dibutyryl cyclic AMP no difference was observed between the control and tumor bearing groups. Clofibrate administered in the diet resulted in a complete elimination of the tumor effect on serum triglycerides and to a great extent prevented the rise in serum cholesterol. The tumor-induced increase in the concentration of the high density lipoproteins was not affected, but the elevation of the d less than 1.063 lipoproteins was not affected, but the elevation of the d less than 1.063 lipoproteins was partially reversed. The increased lipolytic response and accumulation of cyclic AMP following stimulation by ACTH was not altered in adipocytes derived from tumor bearing rats. However, clofibrate treatment resulted in a significantly greater accumulation of cyclic GMP in fat cells stimulated with ACTH from both control and tumor bearing rats. Clofibrate in the diet did not alter the levels of GH or prolactin or serum lipids in the control rats nor were the elevated hormone levels of the tumor bearing rats changed.", "contents": "Experimental hyperlipidemia in rats. Implantation of MtT-F4 tumor, a mammotropic tumor that secretes large quantities of ACTH, GH and prolactin, into male Fisher rats induced the development of hyperlipidemia. Free fatty acid, triglyceride and cholesterol levels in the plasma were significantly increased at 31 days after tumor implantation. Blood glucose and glycerol levels remained normal, while uric acid concentration in the blood was significantly decreased. The concentrations of the serum lipoproteins were significantly increased, while, only small changes in the distribution of the serum lipids and the composition of the lipoproteins were observed. Following stimulation of isolated adipose tissue cells with ACTH, the lipolytic response and the accumulation of cyclic AMP was higher in cells derived from the rats with the tumor, although the accumulation of cyclic GMP was not different from control adipocytes. Further, when the isolated adipose tissue cells were stimulated with dibutyryl cyclic AMP no difference was observed between the control and tumor bearing groups. Clofibrate administered in the diet resulted in a complete elimination of the tumor effect on serum triglycerides and to a great extent prevented the rise in serum cholesterol. The tumor-induced increase in the concentration of the high density lipoproteins was not affected, but the elevation of the d less than 1.063 lipoproteins was not affected, but the elevation of the d less than 1.063 lipoproteins was partially reversed. The increased lipolytic response and accumulation of cyclic AMP following stimulation by ACTH was not altered in adipocytes derived from tumor bearing rats. However, clofibrate treatment resulted in a significantly greater accumulation of cyclic GMP in fat cells stimulated with ACTH from both control and tumor bearing rats. Clofibrate in the diet did not alter the levels of GH or prolactin or serum lipids in the control rats nor were the elevated hormone levels of the tumor bearing rats changed."}
{"id": "PMID:224753", "title": "[Pathology of the polymorphonuclears in dermatology. Methods of investigation. Clinical pictures (author's transl)].", "content": "A remarkable increase in the number of recognized clinical abnormalities of neutrophil function has occurred within the 8 years past. Of major importance in the delineation of these disorders is the establishment of appropriate methodology of their characterization. This review discusses phagocytosis and its disorders by dividing it into stages that encompass the way in which phagocytes ferret out injection, how they recognize pathogens and the intracellular events leading to engulfment and killing of micro-organisms. The pathology of chemotaxis and random mobility is described: the lazy leukocyte syndrome, the Chediak-Higashi syndrome, the familial chemotaxis pecular dermatosis, and a variety of serum abnormalities of the serum complement system associated with deficient generation of chemotactic activity. The second part of these disorders is dailing with the inherited abnormalities of the oxygen dependent killing mechanisms of phagocytes, the chronic granulomatous disease, the glucose-6-phosphate deshydrogenase deficiency, the myeloperoxydase deficiency and the glutathione peroxydase deficiency.", "contents": "[Pathology of the polymorphonuclears in dermatology. Methods of investigation. Clinical pictures (author's transl)]. A remarkable increase in the number of recognized clinical abnormalities of neutrophil function has occurred within the 8 years past. Of major importance in the delineation of these disorders is the establishment of appropriate methodology of their characterization. This review discusses phagocytosis and its disorders by dividing it into stages that encompass the way in which phagocytes ferret out injection, how they recognize pathogens and the intracellular events leading to engulfment and killing of micro-organisms. The pathology of chemotaxis and random mobility is described: the lazy leukocyte syndrome, the Chediak-Higashi syndrome, the familial chemotaxis pecular dermatosis, and a variety of serum abnormalities of the serum complement system associated with deficient generation of chemotactic activity. The second part of these disorders is dailing with the inherited abnormalities of the oxygen dependent killing mechanisms of phagocytes, the chronic granulomatous disease, the glucose-6-phosphate deshydrogenase deficiency, the myeloperoxydase deficiency and the glutathione peroxydase deficiency."}
{"id": "PMID:224754", "title": "Studies on specific antigen content in different fractions of preparations from BLV-producing cell cultures.", "content": "Different protein fractions of BLV-antigens were examined with serological and chemical methods. The fractions of ether resistant and dual antigens were obtained by means of QAE-50A Sephadex chromatography and the fractions of gp-antigen were collected in the course of the affinity chromatography on Concanavalin A-Sepharose. All protein fractions examined by means of polyacrylamide gels electrophoresis occurred to be heterogenous. Some of them showed positive RID or GID reactions with sera of cattle or sheep affected with leukosis. By means of thinlayer chromatography on Sephadex, there were estimated following molecular weights of proteins in the serologically positive fractions: 12.500, 67.000, 70.000 and 150.000.", "contents": "Studies on specific antigen content in different fractions of preparations from BLV-producing cell cultures. Different protein fractions of BLV-antigens were examined with serological and chemical methods. The fractions of ether resistant and dual antigens were obtained by means of QAE-50A Sephadex chromatography and the fractions of gp-antigen were collected in the course of the affinity chromatography on Concanavalin A-Sepharose. All protein fractions examined by means of polyacrylamide gels electrophoresis occurred to be heterogenous. Some of them showed positive RID or GID reactions with sera of cattle or sheep affected with leukosis. By means of thinlayer chromatography on Sephadex, there were estimated following molecular weights of proteins in the serologically positive fractions: 12.500, 67.000, 70.000 and 150.000."}
{"id": "PMID:224755", "title": "Subunit and fine structure of the glycoprotein of bovine leukemia virus.", "content": "The structure of the glycoprotein of bovine leukemia virus (BLV) was investigated. Analysis of BLV under nonreducing conditions revealed two viral glycoproteins with apparent molecular weights of 162,000 (VGP I) and 85,000 (VGP II). After reduction and alkylation, two glycosylated polypeptide chains of apparent molecular weights of 60,000 (gp 60) and 30,000 (gp 30) could be demonstrated in VGP I and VGP II; VGP I appears to contain two molecules of gp 60 and two molecules of gp 30, and VGP II consists of only one molecule of gp 60 and one molecule of gp 30 linked by disulfide bonds. Comparison of the tryptic peptides of gp 60 and gp 30 provided evidence for the existence of partial sequence relationship between gp 60 and gp 30. The structural similarity of the BLV glycoprotein molecule to immunoglobulins is discussed in regard to the possible function of this protein in the pathogenesis of bovine leukemia.", "contents": "Subunit and fine structure of the glycoprotein of bovine leukemia virus. The structure of the glycoprotein of bovine leukemia virus (BLV) was investigated. Analysis of BLV under nonreducing conditions revealed two viral glycoproteins with apparent molecular weights of 162,000 (VGP I) and 85,000 (VGP II). After reduction and alkylation, two glycosylated polypeptide chains of apparent molecular weights of 60,000 (gp 60) and 30,000 (gp 30) could be demonstrated in VGP I and VGP II; VGP I appears to contain two molecules of gp 60 and two molecules of gp 30, and VGP II consists of only one molecule of gp 60 and one molecule of gp 30 linked by disulfide bonds. Comparison of the tryptic peptides of gp 60 and gp 30 provided evidence for the existence of partial sequence relationship between gp 60 and gp 30. The structural similarity of the BLV glycoprotein molecule to immunoglobulins is discussed in regard to the possible function of this protein in the pathogenesis of bovine leukemia."}
{"id": "PMID:224756", "title": "Detection of a precursor of bovine leukemia virus structural proteins in purified virions.", "content": "Gel filtration chromatography of disrupted bovine leukemia virus (BLV) resulted in the isolation of the 25,000 dalton major virion internal protein and two previously uncharacterized virion proteins of molecular weight 65,000 and 12,000 respectively. The 65,000 dalton protein does not bind to concanavalin A and its antigenicity is ether-resistant. Therefore, this polypeptide is different from the previously described glycoprotein associated with BLV. Radiommunoprecipitation and competitive radioimmunoassays indicated that the 65,000 molecular weight polypeptide shares antigenic determinants with the 25,000, 15,000, and 12,000 dalton BLV proteins, respectively. Thus, the 65,000 dalton polypeptide may represent the precursor of these three smaller virion proteins.", "contents": "Detection of a precursor of bovine leukemia virus structural proteins in purified virions. Gel filtration chromatography of disrupted bovine leukemia virus (BLV) resulted in the isolation of the 25,000 dalton major virion internal protein and two previously uncharacterized virion proteins of molecular weight 65,000 and 12,000 respectively. The 65,000 dalton protein does not bind to concanavalin A and its antigenicity is ether-resistant. Therefore, this polypeptide is different from the previously described glycoprotein associated with BLV. Radiommunoprecipitation and competitive radioimmunoassays indicated that the 65,000 molecular weight polypeptide shares antigenic determinants with the 25,000, 15,000, and 12,000 dalton BLV proteins, respectively. Thus, the 65,000 dalton polypeptide may represent the precursor of these three smaller virion proteins."}
{"id": "PMID:224752", "title": "Bilateral hypoglossal nerve paralysis after irradiation therapy.", "content": "Cancericidal doses of irradiation therapy to be the head and neck may be followed by paralysis of cranial nerves due to fibrosis of tissue about the nerves and infiltration of the nerves with fibrous tissue. The hypoglossal nerve is particularly prone to this delayed effect of irradiation therapy and a case is presented here in which there was bilateral hypoglossal paresis appearing three years after therapy.", "contents": "Bilateral hypoglossal nerve paralysis after irradiation therapy. Cancericidal doses of irradiation therapy to be the head and neck may be followed by paralysis of cranial nerves due to fibrosis of tissue about the nerves and infiltration of the nerves with fibrous tissue. The hypoglossal nerve is particularly prone to this delayed effect of irradiation therapy and a case is presented here in which there was bilateral hypoglossal paresis appearing three years after therapy."}
{"id": "PMID:224758", "title": "Heterogeneous properties of BLV-precipitating immunoglobulins in bovine leukemic sera.", "content": "Purified precipitating serum antibodies against bovine leukemia virus present in cattle suffering from various stages of leukosis were identified as immunoglobulins of the IgG 1 subclass and IgA class. Each of these precipitating immunoglobulins exhibited several electrical charges as well as molecular sizes the origin of which will be discussed. Differences in precipitating activities against antigen gp69 and p24 could be observed comparing serum from a suspect animal and a highly leukemic one. In disrupted BLV preparations four antigens were detected immunoelectrophoretically, and two of them could be analyzed. Antigen gp69 less basic than p24 showed a considerably faster mobility.", "contents": "Heterogeneous properties of BLV-precipitating immunoglobulins in bovine leukemic sera. Purified precipitating serum antibodies against bovine leukemia virus present in cattle suffering from various stages of leukosis were identified as immunoglobulins of the IgG 1 subclass and IgA class. Each of these precipitating immunoglobulins exhibited several electrical charges as well as molecular sizes the origin of which will be discussed. Differences in precipitating activities against antigen gp69 and p24 could be observed comparing serum from a suspect animal and a highly leukemic one. In disrupted BLV preparations four antigens were detected immunoelectrophoretically, and two of them could be analyzed. Antigen gp69 less basic than p24 showed a considerably faster mobility."}
{"id": "PMID:224759", "title": "Bovine leukemia virus (BLV) specific RNA in infected cells.", "content": "BLV specific RNA sequences were detected by hybridization to the single stranded DNA copy of the viral RNA in fetal lamb kidney cells infected with bovine leukemia virus (FLK-BLV). The DNA synthesis was carried out in vitro by an endogenous reaction. It was found that uninfected lamb cells do not contain RNA sequences related to the BLV genome, whereas BLV-DNA completely annealed to FLK-BLV RNAs. RNA from FLK-BLV cells contains three species of virus specific RNA which sediment respectively at 35 S, 20--24 S and 12--4 S. In view of their EDTA-sensitive association with ribosomes, viral specific RNA sequences are viral messenger RNAs and their polarity is identical to that of the 70 S viral RNA.", "contents": "Bovine leukemia virus (BLV) specific RNA in infected cells. BLV specific RNA sequences were detected by hybridization to the single stranded DNA copy of the viral RNA in fetal lamb kidney cells infected with bovine leukemia virus (FLK-BLV). The DNA synthesis was carried out in vitro by an endogenous reaction. It was found that uninfected lamb cells do not contain RNA sequences related to the BLV genome, whereas BLV-DNA completely annealed to FLK-BLV RNAs. RNA from FLK-BLV cells contains three species of virus specific RNA which sediment respectively at 35 S, 20--24 S and 12--4 S. In view of their EDTA-sensitive association with ribosomes, viral specific RNA sequences are viral messenger RNAs and their polarity is identical to that of the 70 S viral RNA."}
{"id": "PMID:224760", "title": "Further investigations on the porcine lymphoma C-type particle (PLCP) and the possible biological significance of the virus in pigs.", "content": "The possible biological significance of the procine lymphoma C-type particle (PLCP) was investigated serologically. The screening of 1 200 field sera of apparently normal breeder pigs, performed with an immunodiffusion test, revealed negative results. The same results were obtained with sera from a herd with hereditary lymphosarcoma and with sera from experimentally infected piglets. In cases of doubtful precipitation lines additional tests with a more sensitive indirect immunofluorescence assay were performed. In no case a specific cytoplasmic fluorescence could be observed. The same sera of the 1 200 pigs were tested with BLV antigen as well as 350 bovine sera from BLV-positive cattle were tested with PLCP antigen. A possible antigenic relationship between BLV and PLCP could not be detected by the assays mentioned above. Purified PLCP was compared in SDS-PAGE with MuLV, FeLV, and BLV. The electrophoretical pattern presents suggestive evidence for a typical oncornavirus polypeptide composition. Apart from the presumable major internal protein with a molecular weight of 28 000 d, three low molecular weight proteins appeared at 12 000 d, 11 000 d, and 10 000 d. High molecular weight proteins could not be detected yet. The antigenic specificity of these bands has still to be confirmed.", "contents": "Further investigations on the porcine lymphoma C-type particle (PLCP) and the possible biological significance of the virus in pigs. The possible biological significance of the procine lymphoma C-type particle (PLCP) was investigated serologically. The screening of 1 200 field sera of apparently normal breeder pigs, performed with an immunodiffusion test, revealed negative results. The same results were obtained with sera from a herd with hereditary lymphosarcoma and with sera from experimentally infected piglets. In cases of doubtful precipitation lines additional tests with a more sensitive indirect immunofluorescence assay were performed. In no case a specific cytoplasmic fluorescence could be observed. The same sera of the 1 200 pigs were tested with BLV antigen as well as 350 bovine sera from BLV-positive cattle were tested with PLCP antigen. A possible antigenic relationship between BLV and PLCP could not be detected by the assays mentioned above. Purified PLCP was compared in SDS-PAGE with MuLV, FeLV, and BLV. The electrophoretical pattern presents suggestive evidence for a typical oncornavirus polypeptide composition. Apart from the presumable major internal protein with a molecular weight of 28 000 d, three low molecular weight proteins appeared at 12 000 d, 11 000 d, and 10 000 d. High molecular weight proteins could not be detected yet. The antigenic specificity of these bands has still to be confirmed."}
{"id": "PMID:224762", "title": "Studies on bovine leukosis. VI. Enzyme linked immunosorbent assay for the detection of antibodies to bovine leukosis virus.", "content": "The results of examination of 2 784 sera in the AGIDT-gp were compared with those of the ELISA. A discrepancy was seen in 0.5% of the cases. It was concluded that the ELISA was another useful serological method added to the list of serological techniques presently available for the detection of antibodies to BLV. The advantages of the technique are discussed.", "contents": "Studies on bovine leukosis. VI. Enzyme linked immunosorbent assay for the detection of antibodies to bovine leukosis virus. The results of examination of 2 784 sera in the AGIDT-gp were compared with those of the ELISA. A discrepancy was seen in 0.5% of the cases. It was concluded that the ELISA was another useful serological method added to the list of serological techniques presently available for the detection of antibodies to BLV. The advantages of the technique are discussed."}
{"id": "PMID:224763", "title": "Detection of complement-dependent lytic antibodies in sera from bovine leukemia virus-infected animals.", "content": "Cattle and sheep infected by Bovine Leukemia Virus (BLV) harbor complement-dependent cytotoxic IgG1 antibodies. These antibodies lyse BLV producing cells but are inactive against noncultured tumorous lymphocytes of animals with persistent lymphocytosis. The target structure in the cell membrane contains antigenic determinants of BLV gp 60. The level of cytotoxic activity increases with progression of the disease towards the tumor phase. Sheep vaccinated with inactivated BLV have no cytotoxic activity in the serum but seem to resist infectious BLV challenge. Such cytotoxic activities do not protect the host against tumor growth but strongly control viremia and thus limit BLV spread within bovine and ovine populations.", "contents": "Detection of complement-dependent lytic antibodies in sera from bovine leukemia virus-infected animals. Cattle and sheep infected by Bovine Leukemia Virus (BLV) harbor complement-dependent cytotoxic IgG1 antibodies. These antibodies lyse BLV producing cells but are inactive against noncultured tumorous lymphocytes of animals with persistent lymphocytosis. The target structure in the cell membrane contains antigenic determinants of BLV gp 60. The level of cytotoxic activity increases with progression of the disease towards the tumor phase. Sheep vaccinated with inactivated BLV have no cytotoxic activity in the serum but seem to resist infectious BLV challenge. Such cytotoxic activities do not protect the host against tumor growth but strongly control viremia and thus limit BLV spread within bovine and ovine populations."}
{"id": "PMID:224764", "title": "Indirect hemagglutination test for detection of antibody against bovine leukemia virus.", "content": "An indirect hemagglutination test was developed for detecting antibody against Bovine Leukemia Virus. Medium from Bovine Leukemia Virus infected monolayer fetal lamb kidney cell line cultures was concentrated by a combination of ammonium sulfate precipitation and freezedrying. Tanned sheep red blood cells were exposed to p24 and GP antigens, separately and together. The GP antigen did not attach to the sheep red blood cells, while the p24 antigen did. On testing 150 samples from suspect animals with the crude antigen-coated sheep red blood cells, the indirect hemagglutination test detected almost the same number (74) of positive animals as the agar gel immunodiffusion test with GP antigen (79), and by each of these test a far greater number of cases of leukosis were detected than by hematologic examination (58) or agar gel immunodiffusion test with p24 antigen (44). These results suggest that the indirect hemagglutination test may detect almost the same number of positive as the agar gel immunodiffusion test with GP antigen. Moreover, its results can be read two days earlier, and an impression of the antibody level in the sera is obtained. In routine or large-scale work the indirect hemagglutination test is too troublesome and time-consuming compared to the agar gel immunodiffusion test. The indirect hemagglutination test may be improved if it becomes possible to sensitize sheep red blood cells with GP antigen.", "contents": "Indirect hemagglutination test for detection of antibody against bovine leukemia virus. An indirect hemagglutination test was developed for detecting antibody against Bovine Leukemia Virus. Medium from Bovine Leukemia Virus infected monolayer fetal lamb kidney cell line cultures was concentrated by a combination of ammonium sulfate precipitation and freezedrying. Tanned sheep red blood cells were exposed to p24 and GP antigens, separately and together. The GP antigen did not attach to the sheep red blood cells, while the p24 antigen did. On testing 150 samples from suspect animals with the crude antigen-coated sheep red blood cells, the indirect hemagglutination test detected almost the same number (74) of positive animals as the agar gel immunodiffusion test with GP antigen (79), and by each of these test a far greater number of cases of leukosis were detected than by hematologic examination (58) or agar gel immunodiffusion test with p24 antigen (44). These results suggest that the indirect hemagglutination test may detect almost the same number of positive as the agar gel immunodiffusion test with GP antigen. Moreover, its results can be read two days earlier, and an impression of the antibody level in the sera is obtained. In routine or large-scale work the indirect hemagglutination test is too troublesome and time-consuming compared to the agar gel immunodiffusion test. The indirect hemagglutination test may be improved if it becomes possible to sensitize sheep red blood cells with GP antigen."}
{"id": "PMID:224766", "title": "Characterization of antibodies responsible for the inhibition of BLV induced early polycaryoxytosis.", "content": "A quantitative in vitro assay (EPI) was developed for the serological detection of bovine leukemia virus (BLV) infection in cattle. Positive sera react in inhibiting early polycaryocytosis (EP) induced by BLV. We report here experiments which demonstrate that BLV induced antibodies are responsible for this inhibition. Serum fractionation by gel filtration and affinity chromatography indicates that EP inhibiting activity is mediated by immunoglobulins of the IgG class but not by those of the IgM or other classes. Furthermore, in view of their ion-exchange chromatographic behaviour, these antibodies were attributed to the IgG1 subclass. We also ruled out the participation in the EP inhibition rection of the other compounds like polypeptides, including serum complement and interferon or DNA and RNA. These results demonstrate that EP inhibition by bovine sera is specific of BLV induced antibodies.", "contents": "Characterization of antibodies responsible for the inhibition of BLV induced early polycaryoxytosis. A quantitative in vitro assay (EPI) was developed for the serological detection of bovine leukemia virus (BLV) infection in cattle. Positive sera react in inhibiting early polycaryocytosis (EP) induced by BLV. We report here experiments which demonstrate that BLV induced antibodies are responsible for this inhibition. Serum fractionation by gel filtration and affinity chromatography indicates that EP inhibiting activity is mediated by immunoglobulins of the IgG class but not by those of the IgM or other classes. Furthermore, in view of their ion-exchange chromatographic behaviour, these antibodies were attributed to the IgG1 subclass. We also ruled out the participation in the EP inhibition rection of the other compounds like polypeptides, including serum complement and interferon or DNA and RNA. These results demonstrate that EP inhibition by bovine sera is specific of BLV induced antibodies."}
{"id": "PMID:224767", "title": "Early polykaryocytosis inhibition test: evaluation of its performance in a seroepidemiological survey of bovine leukemia virus induced antibodies in cattle.", "content": "We report the results of a seroepidemiological survey, using the recently described early polykaryocytosis inhibition (EPI) assay to detect bovine leukemia virus (BLV) infection in cattle. At the herd level, there is a good correlation between epidemiological, hematological, anatomopathological data and of both the presence and titer of EP inhibiting antibodies. The EPI procedure revealed to be more sensitive than two other routine serological techniques, complement fixation and immunodiffusion. In addition, at the individual level the average EPI titers of the sera increase progressively from normal to hematologically-suspect, -- positive and finally to lymphosarcomatous animals; when the age is considered, there is a very significant increase of the amount of EP inhibiting antibodies among lymphocytotic animals, while there is only a very moderate increase of the EPI titer among hematologically normal contact animals. This suggests a loss of control of BLV expression in most lymphocytotic animals and may explain the more frequent occurrence of lymphosarcomas in this category of animals. The horizontal transmission of BLV throughout the entire life span is supported by the observation of an increase with age of the percentage of animals with EP inhibiting antibodies.", "contents": "Early polykaryocytosis inhibition test: evaluation of its performance in a seroepidemiological survey of bovine leukemia virus induced antibodies in cattle. We report the results of a seroepidemiological survey, using the recently described early polykaryocytosis inhibition (EPI) assay to detect bovine leukemia virus (BLV) infection in cattle. At the herd level, there is a good correlation between epidemiological, hematological, anatomopathological data and of both the presence and titer of EP inhibiting antibodies. The EPI procedure revealed to be more sensitive than two other routine serological techniques, complement fixation and immunodiffusion. In addition, at the individual level the average EPI titers of the sera increase progressively from normal to hematologically-suspect, -- positive and finally to lymphosarcomatous animals; when the age is considered, there is a very significant increase of the amount of EP inhibiting antibodies among lymphocytotic animals, while there is only a very moderate increase of the EPI titer among hematologically normal contact animals. This suggests a loss of control of BLV expression in most lymphocytotic animals and may explain the more frequent occurrence of lymphosarcomas in this category of animals. The horizontal transmission of BLV throughout the entire life span is supported by the observation of an increase with age of the percentage of animals with EP inhibiting antibodies."}
{"id": "PMID:224769", "title": "An infectivity assay for the bovine leukemia virus based on the induction of the major internal virion antigen in susceptible cell cultures.", "content": "This report described the development of a 7-day infectivity assay for the bovine leukemia virus (BLV) which is based on the induction of the major internal virion antigen (p25) in susceptible indicator monolayer cell cultures. In this assay the antigen is detected in the indicator cells by the immunoperoxidase antibody technique using a monospecific anti-BLV serum. The immunoperoxidase infectivity assay (IPIA) is specific, quantitative, reproducible and more sensitive than the previously developed syncytia induction assay. The IPIA can be applied for the detection of BLV-infected cells and provides a reliable method for the direct diagnosis of BLV infection in cattle.", "contents": "An infectivity assay for the bovine leukemia virus based on the induction of the major internal virion antigen in susceptible cell cultures. This report described the development of a 7-day infectivity assay for the bovine leukemia virus (BLV) which is based on the induction of the major internal virion antigen (p25) in susceptible indicator monolayer cell cultures. In this assay the antigen is detected in the indicator cells by the immunoperoxidase antibody technique using a monospecific anti-BLV serum. The immunoperoxidase infectivity assay (IPIA) is specific, quantitative, reproducible and more sensitive than the previously developed syncytia induction assay. The IPIA can be applied for the detection of BLV-infected cells and provides a reliable method for the direct diagnosis of BLV infection in cattle."}
{"id": "PMID:224770", "title": "Bovine leucosis in Ireland.", "content": "An abbatoir tumour survey showed that lymphosarcoma cases arose at a rate of approximately 2/100,000 cattle slaughtered. No multiple cases occurred in herds. A limited haematological survey showed no evidence of E.B.L. E.B.L. was made a notifiable disease in October 1977. Since then all tumour cases were back-traced and the herd of origin tested by A.G.I.D. test. All herds proved negative. A survey of herds containing imported cattle was started. To date seven herds containing Canadian Holsteins have proved positive serologically. Little spread of infection within the herds has taken place.", "contents": "Bovine leucosis in Ireland. An abbatoir tumour survey showed that lymphosarcoma cases arose at a rate of approximately 2/100,000 cattle slaughtered. No multiple cases occurred in herds. A limited haematological survey showed no evidence of E.B.L. E.B.L. was made a notifiable disease in October 1977. Since then all tumour cases were back-traced and the herd of origin tested by A.G.I.D. test. All herds proved negative. A survey of herds containing imported cattle was started. To date seven herds containing Canadian Holsteins have proved positive serologically. Little spread of infection within the herds has taken place."}
{"id": "PMID:224772", "title": "Epidemiology of bovine leukemia in Venezuela.", "content": "Approximately 20 thousand bovines of autochtonious and imported breeds, located in different regions of the Country were serologically tested by Immuno-diffusion (I.D.) in agar, using BLV GP60 antigens, for the purpose of determining the prevalence of infection by Bovine Leukemia Virus. Hematologic and histopathologic assays were made with the object of determining variations in hematologic values and the determination of stages of persistent lymphocytosis, and of studying the morphocytological changes that accompany malignant transformations of lymphoid elements, in order to make studies on the incidence of clear tumoral lesions in herds highly affected by Leukemia. From 16 thousand samples of serum, tested by the I.D., 6 thousand were positives (37,5%) pertaining to 150 herds distributed in all 20 states of the Country. The sera correspond to different breeds: dairy cattle, beef cattle, brahman, zeb\u00fa hybrids, and buffalo. Hematologically, persistent lymphocytosis induced by the BLV was verified, by previously discarding other pathologic stages with transitory lymphocytosis. Factors which explain this high incidence and the spread of the Bovine Leukemia in Venezuela were detected.", "contents": "Epidemiology of bovine leukemia in Venezuela. Approximately 20 thousand bovines of autochtonious and imported breeds, located in different regions of the Country were serologically tested by Immuno-diffusion (I.D.) in agar, using BLV GP60 antigens, for the purpose of determining the prevalence of infection by Bovine Leukemia Virus. Hematologic and histopathologic assays were made with the object of determining variations in hematologic values and the determination of stages of persistent lymphocytosis, and of studying the morphocytological changes that accompany malignant transformations of lymphoid elements, in order to make studies on the incidence of clear tumoral lesions in herds highly affected by Leukemia. From 16 thousand samples of serum, tested by the I.D., 6 thousand were positives (37,5%) pertaining to 150 herds distributed in all 20 states of the Country. The sera correspond to different breeds: dairy cattle, beef cattle, brahman, zeb\u00fa hybrids, and buffalo. Hematologically, persistent lymphocytosis induced by the BLV was verified, by previously discarding other pathologic stages with transitory lymphocytosis. Factors which explain this high incidence and the spread of the Bovine Leukemia in Venezuela were detected."}
{"id": "PMID:224774", "title": "Enzootic bovine leukosis: an epidemiological survey among cattle in the west of France by precipitating antibody detection.", "content": "In order to inform the sanitary veterinaty authorities, an epidemiological survey was carried out in the West of France to appreciate the level of infection by BLV in cattle. More than 10,000 sera from 763 herds were tested by agar gel immuno-diffusion. The animals were more than one-year-old dairy cattle. 23 sera (0.22%) from 11 herds (1.44%) were found positive. In the 11 herds the levels of serologically positive animals ranged from 1.6 to 40% with a 9% average. These levels are comparatively low and are almost in correspondence with the number of leukotic tumours recorded in the slaughter houses and knackeries.", "contents": "Enzootic bovine leukosis: an epidemiological survey among cattle in the west of France by precipitating antibody detection. In order to inform the sanitary veterinaty authorities, an epidemiological survey was carried out in the West of France to appreciate the level of infection by BLV in cattle. More than 10,000 sera from 763 herds were tested by agar gel immuno-diffusion. The animals were more than one-year-old dairy cattle. 23 sera (0.22%) from 11 herds (1.44%) were found positive. In the 11 herds the levels of serologically positive animals ranged from 1.6 to 40% with a 9% average. These levels are comparatively low and are almost in correspondence with the number of leukotic tumours recorded in the slaughter houses and knackeries."}
{"id": "PMID:224775", "title": "Epidemiologic study on enzootic bovine leukemia in Italy.", "content": "The results obtained from serologic and hematologic investigations conducted on 1.124 cattle belonging to 14 herds located in Central Italy are reported. The results demonstrate a considerable number of animals with antibodies to Bovine Leukemia Virus (BLV) and/or lymphocytosis, coming from Friesian herds with or without history of leucosis. Furthermore it is demonstrated the absence of animals with circulating antibodies to BLV in herds made up of the Chianina breed even with a herd history of leucosis.", "contents": "Epidemiologic study on enzootic bovine leukemia in Italy. The results obtained from serologic and hematologic investigations conducted on 1.124 cattle belonging to 14 herds located in Central Italy are reported. The results demonstrate a considerable number of animals with antibodies to Bovine Leukemia Virus (BLV) and/or lymphocytosis, coming from Friesian herds with or without history of leucosis. Furthermore it is demonstrated the absence of animals with circulating antibodies to BLV in herds made up of the Chianina breed even with a herd history of leucosis."}
{"id": "PMID:224776", "title": "Results of an epidemiological survey of enzootic bovine leukosis in the northern part of Lower Saxony and a preliminary communication of an examination into relationship between BLV-antibody development and calving.", "content": "The Agar-Gel-Immunodiffusion-Test as proposed by EEC has been carried out during the last 2 1/2 years within a defined test area of Lower Saxony. About 500 leukosis-infected herds with a total of about 20.000 head of cattle have been tested five times now within three to six months sequences. The AGIDT has proved to be an easy and very practical test for routine diagnosis in large scale surveys. Our results described again show the superiority of the glykoprotein-antigen over the ether-treated p24-antigen in the AGIDT. Slaughter of AGIDT-reactors within this population led to a fast decrease of leukosis-infection as detected by the test. Epidemiological herd-data show, that spreading of infection within a herd depends largely on direct contact between infected and noninfected animals. Moreover our data give rise to the suspicion that the manipulations during blood-sampling seem to be implicated in the spread of the disease within a herd. Possible reasons for inconsistencies of antibody-titer in infected animals are discussed.", "contents": "Results of an epidemiological survey of enzootic bovine leukosis in the northern part of Lower Saxony and a preliminary communication of an examination into relationship between BLV-antibody development and calving. The Agar-Gel-Immunodiffusion-Test as proposed by EEC has been carried out during the last 2 1/2 years within a defined test area of Lower Saxony. About 500 leukosis-infected herds with a total of about 20.000 head of cattle have been tested five times now within three to six months sequences. The AGIDT has proved to be an easy and very practical test for routine diagnosis in large scale surveys. Our results described again show the superiority of the glykoprotein-antigen over the ether-treated p24-antigen in the AGIDT. Slaughter of AGIDT-reactors within this population led to a fast decrease of leukosis-infection as detected by the test. Epidemiological herd-data show, that spreading of infection within a herd depends largely on direct contact between infected and noninfected animals. Moreover our data give rise to the suspicion that the manipulations during blood-sampling seem to be implicated in the spread of the disease within a herd. Possible reasons for inconsistencies of antibody-titer in infected animals are discussed."}
{"id": "PMID:224777", "title": "Sequential studies of bovine leukemia virus antibody development in dairy cattle over a four-year period.", "content": "Serological examinations using the agar gel immunodiffusion and immunofluorescence tests were undertaken to study: a) the development of bovine leukemia virus infections in a given herd under field conditions monitored by antibody development, b) the reproducibility of the results of serological examination during 22 sequential tests, c) the antibody titre variations amongst individual animals. A total of 286 Friesian cattle representing 2,352 serum samples was tested at regular intervals over a period from 1974/75 to 1978. The percentage of animals with bovine leukemia virus antibodies continuously increased during the observation period from an initial 4.8% (1974/75), 9.7% (1976), 34.2% (1977) to 52.6% (1978). On the basis of 22 sequential tests representing 1,672 serum samples obtained from 76 animals no false positive reactions were seen in the immunodiffusion test. Thirty-six (14.2%) out of 254 animals, however, showed variations of the antibody titre leading to a shift from positive to negative or negative to positive results, respectively. AnothFr three cattle (1.2%) shifted from a positive to negative immunodiffusion result and maintained their negative reactivity for at least two following tests. But they still had specific antibodies if tested by the immunofluorescence test. A detailed analysis of the group of variable reactors supports the view that a more sensitive and quantitative test system may be helpful to complement the presently used immunodiffusion test for the eradication of enzootic bovine leukosis.", "contents": "Sequential studies of bovine leukemia virus antibody development in dairy cattle over a four-year period. Serological examinations using the agar gel immunodiffusion and immunofluorescence tests were undertaken to study: a) the development of bovine leukemia virus infections in a given herd under field conditions monitored by antibody development, b) the reproducibility of the results of serological examination during 22 sequential tests, c) the antibody titre variations amongst individual animals. A total of 286 Friesian cattle representing 2,352 serum samples was tested at regular intervals over a period from 1974/75 to 1978. The percentage of animals with bovine leukemia virus antibodies continuously increased during the observation period from an initial 4.8% (1974/75), 9.7% (1976), 34.2% (1977) to 52.6% (1978). On the basis of 22 sequential tests representing 1,672 serum samples obtained from 76 animals no false positive reactions were seen in the immunodiffusion test. Thirty-six (14.2%) out of 254 animals, however, showed variations of the antibody titre leading to a shift from positive to negative or negative to positive results, respectively. AnothFr three cattle (1.2%) shifted from a positive to negative immunodiffusion result and maintained their negative reactivity for at least two following tests. But they still had specific antibodies if tested by the immunofluorescence test. A detailed analysis of the group of variable reactors supports the view that a more sensitive and quantitative test system may be helpful to complement the presently used immunodiffusion test for the eradication of enzootic bovine leukosis."}
{"id": "PMID:224780", "title": "BLV-antibodies in serial sampling over five years in a bovine leukosis herd.", "content": "The sequential monthly bleedings of bovine leukosis herd animals showed that a majority of the animals was positive for BLV-antibodies at the age of 1 1/2 years or over and remained reactors throughout the observation period. Two phases of BLV-antibodies were observed in the calves born in the herd. In the first phase the calves remained reactors for two to seven months, indicating residual maternal antibodies acquired through colostrum. In the second phase, the animals became permanent reactors reflecting an active concomitant infection with BLV. The degree of spread of BLV infection among the leukosis herd animals appeared to depend upon the ratio between reactors and negative animals.", "contents": "BLV-antibodies in serial sampling over five years in a bovine leukosis herd. The sequential monthly bleedings of bovine leukosis herd animals showed that a majority of the animals was positive for BLV-antibodies at the age of 1 1/2 years or over and remained reactors throughout the observation period. Two phases of BLV-antibodies were observed in the calves born in the herd. In the first phase the calves remained reactors for two to seven months, indicating residual maternal antibodies acquired through colostrum. In the second phase, the animals became permanent reactors reflecting an active concomitant infection with BLV. The degree of spread of BLV infection among the leukosis herd animals appeared to depend upon the ratio between reactors and negative animals."}
{"id": "PMID:224781", "title": "An evaluation of the role of milk in the natural transmission of BLV.", "content": "In order to evaluate the role of milk in the transmission of BLV, the presence of the virus and viral antibodies was investigated in cattle that were born to, and nursed on, infected dams and then raised in isolation or in contact with infected animals. Only 3 of the 17 isolated cattle became infected during 25-29 months of observation. During the same period of time, all 17 cattle raised in contact with BLV-positive animals developed BLV infection. From these results, it is apparent that milk-borne transmission of BLV, if it occurs, is much less frequent than contact transmission.", "contents": "An evaluation of the role of milk in the natural transmission of BLV. In order to evaluate the role of milk in the transmission of BLV, the presence of the virus and viral antibodies was investigated in cattle that were born to, and nursed on, infected dams and then raised in isolation or in contact with infected animals. Only 3 of the 17 isolated cattle became infected during 25-29 months of observation. During the same period of time, all 17 cattle raised in contact with BLV-positive animals developed BLV infection. From these results, it is apparent that milk-borne transmission of BLV, if it occurs, is much less frequent than contact transmission."}
{"id": "PMID:224782", "title": "Horizontal transmission studies on enzootic bovine leukosis.", "content": "Four groups of sero-negative cattle were brought into contact for various periods with either sero-positive and antigen-negative or sero- as well as antigen-positive animals. A seroconversion as evidence of transmission was only detected in animals that had been in contact with sero- and antigen-positive cattle. Shortest period of contact for those was 2 months after which a seroconversion was found. A distinct elevation of the number of lymphocytes was only detected in two animals which had been transported shortly after evidence of the seroconversion had occured.", "contents": "Horizontal transmission studies on enzootic bovine leukosis. Four groups of sero-negative cattle were brought into contact for various periods with either sero-positive and antigen-negative or sero- as well as antigen-positive animals. A seroconversion as evidence of transmission was only detected in animals that had been in contact with sero- and antigen-positive cattle. Shortest period of contact for those was 2 months after which a seroconversion was found. A distinct elevation of the number of lymphocytes was only detected in two animals which had been transported shortly after evidence of the seroconversion had occured."}
{"id": "PMID:224783", "title": "Tumor-associated antigen and cell surface marker in cells of bovine lymphosarcoma.", "content": "The detection of tumor-associated antigen and B cell surface marker was attempted in lymphoid cells of peripheral blood (PBL) and lymph nodes obtained from cattle with lymphosarcoma, cattle infected with bovine leukosis virus (BLV), and clinically normal cattle. As a result, specific tumor-associated antigen was found in PBL and lymphoid tumor cells from cattle with the adult form of lymphosarcoma (ALS) using anti-ALS serum. The antigen was also detected in PBL of BLV-infected cattle. A weak reaction for the antigen was found in 2 of 5 cases of calf form. No significant reaction for the tumor-associated antigen of neoplastic lymphoid cells from ALS was found in the thymic and skin forms. The percentage of B cells in PBL and lymph nodes from ALS was higher than that in normal cattle. However, a loss of B cell surface marker was suggested in some ALS cases. A good relation was obtained between an increased B cell percentage and an appearance of the tumor-associated antigen in PBL of BLV-infected cattle. In lymphoid cells of PBL and lymph nodes from sporadic cases, the percentage of B cells was lower than that observed in normal cattle.", "contents": "Tumor-associated antigen and cell surface marker in cells of bovine lymphosarcoma. The detection of tumor-associated antigen and B cell surface marker was attempted in lymphoid cells of peripheral blood (PBL) and lymph nodes obtained from cattle with lymphosarcoma, cattle infected with bovine leukosis virus (BLV), and clinically normal cattle. As a result, specific tumor-associated antigen was found in PBL and lymphoid tumor cells from cattle with the adult form of lymphosarcoma (ALS) using anti-ALS serum. The antigen was also detected in PBL of BLV-infected cattle. A weak reaction for the antigen was found in 2 of 5 cases of calf form. No significant reaction for the tumor-associated antigen of neoplastic lymphoid cells from ALS was found in the thymic and skin forms. The percentage of B cells in PBL and lymph nodes from ALS was higher than that in normal cattle. However, a loss of B cell surface marker was suggested in some ALS cases. A good relation was obtained between an increased B cell percentage and an appearance of the tumor-associated antigen in PBL of BLV-infected cattle. In lymphoid cells of PBL and lymph nodes from sporadic cases, the percentage of B cells was lower than that observed in normal cattle."}
{"id": "PMID:224785", "title": "Distribution of bovine leukemia virus proviral sequences in tissues of bovine, ovine and human origin.", "content": "Bovine leukemia virus (BLV) single-stranded cDNA was used to study the distribution of DNA sequences in tissues (normal or malignant) from bovine, ovine and human origin. After recycling against normal bovine DNA, BLV (3H) cDNA hybridized with bovine enzootic tumor DNA but did not hybridize with normal bovine DNA. These results indicate that BLV is an exogenous RNA oncogenic virus and confirm that enzootic bovine leukosis (EBL) is an infectious disease. Proviral BLV sequences were also detected in buffy coat cells of animals in persistent lymphocytosis (PL) and carrying antibodies to BLV but no tumors. In animals at the tumor stage of EBL, the proviral sequences were found in buffy coat cells, in solid tumors (lymphosarcomas) and in organs infiltrated with tumoral lymphoid cells but not in apparently normal organs. No hybridization above background was observed between BLV (3H) cDNA and DNAs extracted from buffy coat cells and tumors corresponding to sporadic forms of bovine leukosis and some human leukemias and sarcomas.", "contents": "Distribution of bovine leukemia virus proviral sequences in tissues of bovine, ovine and human origin. Bovine leukemia virus (BLV) single-stranded cDNA was used to study the distribution of DNA sequences in tissues (normal or malignant) from bovine, ovine and human origin. After recycling against normal bovine DNA, BLV (3H) cDNA hybridized with bovine enzootic tumor DNA but did not hybridize with normal bovine DNA. These results indicate that BLV is an exogenous RNA oncogenic virus and confirm that enzootic bovine leukosis (EBL) is an infectious disease. Proviral BLV sequences were also detected in buffy coat cells of animals in persistent lymphocytosis (PL) and carrying antibodies to BLV but no tumors. In animals at the tumor stage of EBL, the proviral sequences were found in buffy coat cells, in solid tumors (lymphosarcomas) and in organs infiltrated with tumoral lymphoid cells but not in apparently normal organs. No hybridization above background was observed between BLV (3H) cDNA and DNAs extracted from buffy coat cells and tumors corresponding to sporadic forms of bovine leukosis and some human leukemias and sarcomas."}
{"id": "PMID:224786", "title": "Development of bovine leukosis virus infection in cattle. A preliminary study.", "content": "A serological study in three herds for 5 to 7 years indicated that BLV infection usually developed when cows where 2 to 4 years old, thereafter, the rate of new infection was somewhat less. The reactor status of the dam had no influence on whether or not and when progeny became reactors. In only one herd 3 calves from 57 reactor cows become persistent reactors, thus there was little evidence of vertical transmission. Such can occur where there is a break in the placental barrier.", "contents": "Development of bovine leukosis virus infection in cattle. A preliminary study. A serological study in three herds for 5 to 7 years indicated that BLV infection usually developed when cows where 2 to 4 years old, thereafter, the rate of new infection was somewhat less. The reactor status of the dam had no influence on whether or not and when progeny became reactors. In only one herd 3 calves from 57 reactor cows become persistent reactors, thus there was little evidence of vertical transmission. Such can occur where there is a break in the placental barrier."}
{"id": "PMID:224787", "title": "Persistent lymphocytosis in cattle: its cause, nature and relation to lymphosarcoma.", "content": "Studies in well-characterized cattle populations strongly support the view that the bovine leukemia virus (BLV) is the causative agent of the adult (enzootic) form of bovine lymphosarcoma and persistent lymphocytosis (PL), and that host genetic factors play an important role in the development of these two conditions. On the other hand, the available information indicates that the genetic factors controlling the development of PL are frequently independent of those controlling the development of lymphosarcoma. There is no evidence that clinically normal cattle with PL harbor malignant cells or have any other clinical abnormality. In these animals lymphocytosis results from the expansion of two distinct subpopulations of non-neoplastic B lymphocytes, one of which is free of BLV. Long-term studies have shown that the large majority of cattle with PL do not develop lymphosarcoma even when kept to advanced age. These data indicate that PL is not a disease nor a preclinical stage of lymphosarcoma. Rather PL should be considered as a benign response to BLV infection which, although frequently associated with lymphosarcoma, is independant of it.", "contents": "Persistent lymphocytosis in cattle: its cause, nature and relation to lymphosarcoma. Studies in well-characterized cattle populations strongly support the view that the bovine leukemia virus (BLV) is the causative agent of the adult (enzootic) form of bovine lymphosarcoma and persistent lymphocytosis (PL), and that host genetic factors play an important role in the development of these two conditions. On the other hand, the available information indicates that the genetic factors controlling the development of PL are frequently independent of those controlling the development of lymphosarcoma. There is no evidence that clinically normal cattle with PL harbor malignant cells or have any other clinical abnormality. In these animals lymphocytosis results from the expansion of two distinct subpopulations of non-neoplastic B lymphocytes, one of which is free of BLV. Long-term studies have shown that the large majority of cattle with PL do not develop lymphosarcoma even when kept to advanced age. These data indicate that PL is not a disease nor a preclinical stage of lymphosarcoma. Rather PL should be considered as a benign response to BLV infection which, although frequently associated with lymphosarcoma, is independant of it."}
{"id": "PMID:224788", "title": "A new antiviral agent (P2) in the purpose of treatment of bovine leukemia.", "content": "Thirty five cows and heifers, all positive reactors on ID test and all showing persistent lymphocytosis (15 with markedly enlarged lymphatic glands) were divided in 4 experimental groups and treated with P-2, a new antiviral agent, previously shown to be effective for several RNA type viruses. In table are indicated groups, range of dosages of P-2, and variability in WBC and lymphocyte. White blood cells found to be at the lowest level (P less than 0.02) one month after treatment with P-2, a less marked reduction (P less than 0.05) was found when the experiments ended at 7 months. A significant (P less than 0.05) fall in lymphocytes was found one month after treatment but this was not significant at the end of experiment. In 12 animals with lymphosarcomatous disease significant retraction of lymphatic glands. It is not clear whether the sudden drop in WBC and lymphocytes is due to the virostatic effect of drug or an effect of drug per se. New series of experiments will be made to treat BLV with two agents: one virostatic and other cytostatic.", "contents": "A new antiviral agent (P2) in the purpose of treatment of bovine leukemia. Thirty five cows and heifers, all positive reactors on ID test and all showing persistent lymphocytosis (15 with markedly enlarged lymphatic glands) were divided in 4 experimental groups and treated with P-2, a new antiviral agent, previously shown to be effective for several RNA type viruses. In table are indicated groups, range of dosages of P-2, and variability in WBC and lymphocyte. White blood cells found to be at the lowest level (P less than 0.02) one month after treatment with P-2, a less marked reduction (P less than 0.05) was found when the experiments ended at 7 months. A significant (P less than 0.05) fall in lymphocytes was found one month after treatment but this was not significant at the end of experiment. In 12 animals with lymphosarcomatous disease significant retraction of lymphatic glands. It is not clear whether the sudden drop in WBC and lymphocytes is due to the virostatic effect of drug or an effect of drug per se. New series of experiments will be made to treat BLV with two agents: one virostatic and other cytostatic."}
{"id": "PMID:224792", "title": "Preliminary results of a new sanitation program for the eradication of enzootic bovine leukosis.", "content": "The program under discussion is based on results obtained during transmission studies in which specific antibodies were detected in the immunodiffusion test earlier than antigen in peripheral blood leukocytes. Furthermore, it could be demonstrated that seroconversion does not seem to occur later than 3 months after transmission of the infectious agent. The results obtained in 11 herds are presented. The program is as follows: when the result of the immunodiffusion test becomes available all positive animals above 6 months of age are immediately removed from the herd. The remaining animals are checked at intervals of 3 months and sero-positives are always instantly removed. In pursuing the program a number of herds have obviously reachend 2 years old.", "contents": "Preliminary results of a new sanitation program for the eradication of enzootic bovine leukosis. The program under discussion is based on results obtained during transmission studies in which specific antibodies were detected in the immunodiffusion test earlier than antigen in peripheral blood leukocytes. Furthermore, it could be demonstrated that seroconversion does not seem to occur later than 3 months after transmission of the infectious agent. The results obtained in 11 herds are presented. The program is as follows: when the result of the immunodiffusion test becomes available all positive animals above 6 months of age are immediately removed from the herd. The remaining animals are checked at intervals of 3 months and sero-positives are always instantly removed. In pursuing the program a number of herds have obviously reachend 2 years old."}
{"id": "PMID:224793", "title": "Studies on bovine leukosis as it is seen in England and Wales.", "content": "A random series of 14 clinical cases of bovine leukosis as it is seen in England and Wales has been studied clinically, haematologically, serologically (by the indirect fluorescent antibody test and later by agar gel immunodiffusion as well), virologically (for evidence of bovine leukaemia virus--BLV) and using the electron microsocope to count intranuclear pockets in circulating lymphocytes. Additionally calves have been inoculated with whole blood and a tissue lymphocyte suspension from the first six cases and the experimental calves studied periodically by the same methods. Herds of origin of the field cases were examined for clinical evidence of lymphomatosis, for evidence of leukaemia and for serum antibody to BLV. To date no evidence has been found to indicate that the field cases were other than sporadic and non-contagious. Neither BLV nor specific antibody has been demonstrated; no increase in lymphocytic nuclear pockets has been seen; the transmission tests are still apparently negative. It would appear that sporadic bovine leukosis and enzootic bovine leukosis are aetiologically separate entities.", "contents": "Studies on bovine leukosis as it is seen in England and Wales. A random series of 14 clinical cases of bovine leukosis as it is seen in England and Wales has been studied clinically, haematologically, serologically (by the indirect fluorescent antibody test and later by agar gel immunodiffusion as well), virologically (for evidence of bovine leukaemia virus--BLV) and using the electron microsocope to count intranuclear pockets in circulating lymphocytes. Additionally calves have been inoculated with whole blood and a tissue lymphocyte suspension from the first six cases and the experimental calves studied periodically by the same methods. Herds of origin of the field cases were examined for clinical evidence of lymphomatosis, for evidence of leukaemia and for serum antibody to BLV. To date no evidence has been found to indicate that the field cases were other than sporadic and non-contagious. Neither BLV nor specific antibody has been demonstrated; no increase in lymphocytic nuclear pockets has been seen; the transmission tests are still apparently negative. It would appear that sporadic bovine leukosis and enzootic bovine leukosis are aetiologically separate entities."}
{"id": "PMID:224794", "title": "Leucosis in cattle in the Netherlands.", "content": "It is stated with certainty that enzootic bovine leucosis never has been encountered in autochtonous Dutch cattle. After 1965 when due to E.C. regulations the import of cattle from partner countries was facilitated, several cases of E.B.L. were found in imported cattle and sometimes these cattle caused outbreaks on Dutch farms. A review is given of the control of the disease since that time and of the official eradication system that started in May 1977. Reports are given of some case histories, the policy of the eradication under the national circumstances and the status of the disease on this moment.", "contents": "Leucosis in cattle in the Netherlands. It is stated with certainty that enzootic bovine leucosis never has been encountered in autochtonous Dutch cattle. After 1965 when due to E.C. regulations the import of cattle from partner countries was facilitated, several cases of E.B.L. were found in imported cattle and sometimes these cattle caused outbreaks on Dutch farms. A review is given of the control of the disease since that time and of the official eradication system that started in May 1977. Reports are given of some case histories, the policy of the eradication under the national circumstances and the status of the disease on this moment."}
{"id": "PMID:224796", "title": "Problems of bovine leucosis control and prophylaxis in industrial breeding conditions.", "content": "Industrial cattle-breeding in Bulgaria is characterized by large cattle-breeding complexes holding 500, 1,000 or 2,000 dairy cows; farms specialized in rearing calves for breeding purposes, and calves fattening units holding 2,000, 5,000 or 10,000 animals. A specific technology has been introduced for management purposes. This high concentration and specialization creates specific organisational problems for antiepizootic control measures. Bovine leucosis has been brought from abroad by imported breedings animals. A complex system for leucosis prophylaxis and control is obligatorily implemented. It is supervized and financed by the state. Particular care is taken of ensuring protective measures for import breeding animals. The infected farms are put under strict quarantine. The animals which show a positive reaction during complex diagnostic tests are slaughtered and the meat is used after heat-processing. The milk is heat-processed too and sent for further utilization. Calves born in infected farms are not fit for breeding purposes but for fattening only.", "contents": "Problems of bovine leucosis control and prophylaxis in industrial breeding conditions. Industrial cattle-breeding in Bulgaria is characterized by large cattle-breeding complexes holding 500, 1,000 or 2,000 dairy cows; farms specialized in rearing calves for breeding purposes, and calves fattening units holding 2,000, 5,000 or 10,000 animals. A specific technology has been introduced for management purposes. This high concentration and specialization creates specific organisational problems for antiepizootic control measures. Bovine leucosis has been brought from abroad by imported breedings animals. A complex system for leucosis prophylaxis and control is obligatorily implemented. It is supervized and financed by the state. Particular care is taken of ensuring protective measures for import breeding animals. The infected farms are put under strict quarantine. The animals which show a positive reaction during complex diagnostic tests are slaughtered and the meat is used after heat-processing. The milk is heat-processed too and sent for further utilization. Calves born in infected farms are not fit for breeding purposes but for fattening only."}
{"id": "PMID:224797", "title": "[Physio-pathology of pseudohypoparathyroidism (author's transl)].", "content": "A case of pseudohypoparathyroidism has been investigated. Indirect evidence allows to eliminate a defect of renal 1 alpha-hydroxylase as the determining factor of this condition. Similarly, the increased size of the mean surface area of the cross-section of periosteocytic lacunae, as determined on decalcified sections of bone obtained by transiliac biopsy, shows the osteocytes to be sensitive to the endogenous PTH, discarding cAMP response to PTH in bone as a prerequisite for PTH action on bone. The authors conclude from these data and from previous experiments that the defect of parathyroid function in this condition probably relates to the existence of an abnormal PTH molecule and/or metabolism and/or interaction with the receptors sites. The endocrine function was studied as well. Prediabetes was demonstrated, as well as primary latent hypothyroidism (TRH test). Prolactin release could not be stimulated by TRH, levodopa, metoclopramide, chlorpromazine and insulin hypoglycemia. The latter produced a normal release of ACTH (as ascertained by plasma cortisol levels) and GH, and possibly a sluggish response of glucagon and gastrin. There was a deficiency of urinary concentration upon restriction of fluid intake. This was only partially corrected by ADH administration.", "contents": "[Physio-pathology of pseudohypoparathyroidism (author's transl)]. A case of pseudohypoparathyroidism has been investigated. Indirect evidence allows to eliminate a defect of renal 1 alpha-hydroxylase as the determining factor of this condition. Similarly, the increased size of the mean surface area of the cross-section of periosteocytic lacunae, as determined on decalcified sections of bone obtained by transiliac biopsy, shows the osteocytes to be sensitive to the endogenous PTH, discarding cAMP response to PTH in bone as a prerequisite for PTH action on bone. The authors conclude from these data and from previous experiments that the defect of parathyroid function in this condition probably relates to the existence of an abnormal PTH molecule and/or metabolism and/or interaction with the receptors sites. The endocrine function was studied as well. Prediabetes was demonstrated, as well as primary latent hypothyroidism (TRH test). Prolactin release could not be stimulated by TRH, levodopa, metoclopramide, chlorpromazine and insulin hypoglycemia. The latter produced a normal release of ACTH (as ascertained by plasma cortisol levels) and GH, and possibly a sluggish response of glucagon and gastrin. There was a deficiency of urinary concentration upon restriction of fluid intake. This was only partially corrected by ADH administration."}
{"id": "PMID:224798", "title": "The interaction of radioiodinated thyrotropin with human plasma membranes from normal and diseased thyroid glands. Relation of thyrotropin binding to adenylate cyclase activity.", "content": "Plasma membranes have been purified from homogenates of normal human thyroid glands and multinodular euthyroid and Graves' goitres by discontinuous sucrose gradient centrifugation. Preparations of reasonable purity were obtained containing specific binding sites for thyrotropin and thyrotropin-sensitive adenylate cyclase. Optimum conditions for 125I-labeled thyrotropin binding were pH 7.8 and 37 degrees C. Sodium ions and concentration of Tris above 20 mM reduced thyrotropin binding. Human plasma membranes showed no species specificity toward thyrotropins from 3 different species (ox, hog and man). Displacement curves of I125-labeled bovine thyrotropin by unlabeled hormones was in the order of increasing concentrations of bovine, porcine and human highly purified thyrotropins and was inversely related to the specific biological activity of these preparations as determined by the bioassay in the mouse. Analysis of the interaction between membranes and 125I-labeled thyrotropin resulted in curvilinear Scatchard plots which can indicate the presence of two types of sites with high affinity -- low capacity (KD = 5 nM) and low affinity -- high capacity (KD = 500 nM) or site -- site interaction of the negative cooperativity type. No significant difference in binding site characteristics was found in normal and diseased glands (multinodular and Graves' goitres). A good correlation was found at equilibrium and in the conditions of adenylate cyclase assay between receptor occupancy and cyclase activation by b-thyrotropin.", "contents": "The interaction of radioiodinated thyrotropin with human plasma membranes from normal and diseased thyroid glands. Relation of thyrotropin binding to adenylate cyclase activity. Plasma membranes have been purified from homogenates of normal human thyroid glands and multinodular euthyroid and Graves' goitres by discontinuous sucrose gradient centrifugation. Preparations of reasonable purity were obtained containing specific binding sites for thyrotropin and thyrotropin-sensitive adenylate cyclase. Optimum conditions for 125I-labeled thyrotropin binding were pH 7.8 and 37 degrees C. Sodium ions and concentration of Tris above 20 mM reduced thyrotropin binding. Human plasma membranes showed no species specificity toward thyrotropins from 3 different species (ox, hog and man). Displacement curves of I125-labeled bovine thyrotropin by unlabeled hormones was in the order of increasing concentrations of bovine, porcine and human highly purified thyrotropins and was inversely related to the specific biological activity of these preparations as determined by the bioassay in the mouse. Analysis of the interaction between membranes and 125I-labeled thyrotropin resulted in curvilinear Scatchard plots which can indicate the presence of two types of sites with high affinity -- low capacity (KD = 5 nM) and low affinity -- high capacity (KD = 500 nM) or site -- site interaction of the negative cooperativity type. No significant difference in binding site characteristics was found in normal and diseased glands (multinodular and Graves' goitres). A good correlation was found at equilibrium and in the conditions of adenylate cyclase assay between receptor occupancy and cyclase activation by b-thyrotropin."}
{"id": "PMID:224799", "title": "[Bovine chromosome mapping with the cell hybridization technic. Localization on the x chromosome of glucose-6-phosphate dehydrogenase, phosphoglycerate kinase, alpha-galactosidase A and hypoxanthine phosphoribosyltransferase].", "content": "Twelve hamster x cattle (Bos taurus) cell hybrids showed loss of cattle chromosomes, which allows their use for chromosome mapping of cattle. Genes coding for G6PD, alpha-GAL A, PGK, and (indirectly) HGPRT are synteneic and localized on the X chromosome.", "contents": "[Bovine chromosome mapping with the cell hybridization technic. Localization on the x chromosome of glucose-6-phosphate dehydrogenase, phosphoglycerate kinase, alpha-galactosidase A and hypoxanthine phosphoribosyltransferase]. Twelve hamster x cattle (Bos taurus) cell hybrids showed loss of cattle chromosomes, which allows their use for chromosome mapping of cattle. Genes coding for G6PD, alpha-GAL A, PGK, and (indirectly) HGPRT are synteneic and localized on the X chromosome."}
{"id": "PMID:224800", "title": "Hyperexcitability of motor and sensory neurons in neuromyotonia.", "content": "Two members of a family with a neuropathy resembling Charcot-Marie-Tooth disease were unable to relax their muscles after voluntary contraction. Muscle spasm often outlasted voluntary contraction by 30 seconds or more before subsiding into myokymia and fasciculations. The posture of the hand during muscle spasm resembled that of tetany, and Trousseau's and Chvostek's signs were present although no abnormality of calcium or magnesium metabolism could be demonstrated. Muscle spasms ceased during medication with carbamazepine, 600 mg daily. Nerve stimulation, electromyography, and regional neuromuscular blockade with curare indicated that the condition originated in peripheral nerve, while microneurographic recordings showed that sensory as well as motor fibers were hyperexcitable. Sural nerve biopsy revealed axonal degeneration involving myelinated and unmyelinated fibers. It was concluded that the neural hyperexcitability is caused by a membrane defect resulting in a low threshold for excitation throughout the length of the axon.", "contents": "Hyperexcitability of motor and sensory neurons in neuromyotonia. Two members of a family with a neuropathy resembling Charcot-Marie-Tooth disease were unable to relax their muscles after voluntary contraction. Muscle spasm often outlasted voluntary contraction by 30 seconds or more before subsiding into myokymia and fasciculations. The posture of the hand during muscle spasm resembled that of tetany, and Trousseau's and Chvostek's signs were present although no abnormality of calcium or magnesium metabolism could be demonstrated. Muscle spasms ceased during medication with carbamazepine, 600 mg daily. Nerve stimulation, electromyography, and regional neuromuscular blockade with curare indicated that the condition originated in peripheral nerve, while microneurographic recordings showed that sensory as well as motor fibers were hyperexcitable. Sural nerve biopsy revealed axonal degeneration involving myelinated and unmyelinated fibers. It was concluded that the neural hyperexcitability is caused by a membrane defect resulting in a low threshold for excitation throughout the length of the axon."}
{"id": "PMID:224801", "title": "Activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase in human cerebrospinal fluid.", "content": "Activity of the myelin marker enzyme 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) was assayed in cerebrospinal fluid samples obtained from patients with multiple sclerosis (MS) and other neurological diseases. The enzyme activity was found to be elevated in acute cases of MS and reduced during remission. It was present in other demyelinating diseases, and no activity was detected in normal CSF. CNP may be released into CSF from any insult to myelin. The level of activity appears to reflect demyelination and the rate of breakdown of the myelin sheath.", "contents": "Activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase in human cerebrospinal fluid. Activity of the myelin marker enzyme 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) was assayed in cerebrospinal fluid samples obtained from patients with multiple sclerosis (MS) and other neurological diseases. The enzyme activity was found to be elevated in acute cases of MS and reduced during remission. It was present in other demyelinating diseases, and no activity was detected in normal CSF. CNP may be released into CSF from any insult to myelin. The level of activity appears to reflect demyelination and the rate of breakdown of the myelin sheath."}
{"id": "PMID:224808", "title": "Preliminary studies of the mode of action of arildone, a novel antiviral agent.", "content": "Arildone (also known as Win 38020), a novel aryl diketone, inhibited replication of herpes simplex virus type 2 in tissue culture by interfering with an event that occurs prior to 6 h postinfection. The inhibition could be partially reversed by washing. Although the exact mechanism of action is unknown, neither viral deoxyribonucleic acid nor viral proteins were synthesized in the presence of arildone.", "contents": "Preliminary studies of the mode of action of arildone, a novel antiviral agent. Arildone (also known as Win 38020), a novel aryl diketone, inhibited replication of herpes simplex virus type 2 in tissue culture by interfering with an event that occurs prior to 6 h postinfection. The inhibition could be partially reversed by washing. Although the exact mechanism of action is unknown, neither viral deoxyribonucleic acid nor viral proteins were synthesized in the presence of arildone."}
{"id": "PMID:224809", "title": "Effect of 5-iodo-5'-amino-2',5'-dideoxyuridine on varicella-zoster virus in vitro.", "content": "The antiviral effect of the nucleoside analog 5-iodo-5'-amino-2',5'-dideoxyuridine (AIU) was tested with three isolates of varicella-zoster virus (VZV). AIU concentrations of 10 to 800 muM (3.5 to 288 mug/ml) reduced the number of plaques produced by VZV-infected cells and cell-free VZV from approximately 30 to 95%. Smaller plaque size was also observed in the presence of AIU. AIU was less effective than arabinofuranosylthymine in reducing VZV-induced plaques since as little as 5 mug of arabinofuranosylthymine per ml completely blocked plaque formation by cell-free VZV. Toxicity assays with human diploid embryo fibroblast cells were also carried out. Drug concentrations as high as 800 muM were not toxic to human diploid embryo fibroblast cells as determined by radiolabeling of cell deoxyribonucleic acid, ribonucleic acid, and protein.", "contents": "Effect of 5-iodo-5'-amino-2',5'-dideoxyuridine on varicella-zoster virus in vitro. The antiviral effect of the nucleoside analog 5-iodo-5'-amino-2',5'-dideoxyuridine (AIU) was tested with three isolates of varicella-zoster virus (VZV). AIU concentrations of 10 to 800 muM (3.5 to 288 mug/ml) reduced the number of plaques produced by VZV-infected cells and cell-free VZV from approximately 30 to 95%. Smaller plaque size was also observed in the presence of AIU. AIU was less effective than arabinofuranosylthymine in reducing VZV-induced plaques since as little as 5 mug of arabinofuranosylthymine per ml completely blocked plaque formation by cell-free VZV. Toxicity assays with human diploid embryo fibroblast cells were also carried out. Drug concentrations as high as 800 muM were not toxic to human diploid embryo fibroblast cells as determined by radiolabeling of cell deoxyribonucleic acid, ribonucleic acid, and protein."}
{"id": "PMID:224823", "title": "Extragonadal germ-cell tumours.", "content": "The case histories of two patients with an extragonadal germ-cell tumour are discussed. One had a retroperitoneal embryonal carcinoma, and the other had a mediastinal choriocarcinoma-seminoma. The pathogenesis, symptomatology, diagnosis and treatment of these rare tumours are discussed in some detail.?", "contents": "Extragonadal germ-cell tumours. The case histories of two patients with an extragonadal germ-cell tumour are discussed. One had a retroperitoneal embryonal carcinoma, and the other had a mediastinal choriocarcinoma-seminoma. The pathogenesis, symptomatology, diagnosis and treatment of these rare tumours are discussed in some detail.?"}
{"id": "PMID:224824", "title": "A year's experience of the rotavirus syndrome and its association with respiratory illness.", "content": "In a hospital study rotavirus was identified in 51% of 152 children with diarrhoea. These patients showed a clinical pattern that was distinct from patients in whom the diarrhoea was associated with bacteria, other viruses, or no pathogens. A respiratory illness was described in 66% of rotavirus patients and usually preceded the gastrointestinal symptoms. Vomiting lasted between one and 3 days and was curtailed by substituting the normal diet with clear fluids. Watery diarrhoes continued for 4 or 5 days, even when rehydration was by the intravenous rather than the oral route. Prolonged diarrhoea was rare. Most children infected with rotavirus were under 2 years of age, but dehydration was most severe in infants aged between 12 and 18 months. A clinician can thus recognise the rotavirus syndrome and expect spontaneous recovery if adequate rehydration is maintained for a critical few days.", "contents": "A year's experience of the rotavirus syndrome and its association with respiratory illness. In a hospital study rotavirus was identified in 51% of 152 children with diarrhoea. These patients showed a clinical pattern that was distinct from patients in whom the diarrhoea was associated with bacteria, other viruses, or no pathogens. A respiratory illness was described in 66% of rotavirus patients and usually preceded the gastrointestinal symptoms. Vomiting lasted between one and 3 days and was curtailed by substituting the normal diet with clear fluids. Watery diarrhoes continued for 4 or 5 days, even when rehydration was by the intravenous rather than the oral route. Prolonged diarrhoea was rare. Most children infected with rotavirus were under 2 years of age, but dehydration was most severe in infants aged between 12 and 18 months. A clinician can thus recognise the rotavirus syndrome and expect spontaneous recovery if adequate rehydration is maintained for a critical few days."}
{"id": "PMID:224825", "title": "Recurrent attack of rotavirus gastroenteritis after adenovirus-induced diarrhoea.", "content": "A 14-month-old baby boy suffered a second attack of rotavirus gastroenteritis within one month of the initial one. The second attack followed a diarrhoeal episode associated with adenovirus. Gastrointestinal symptoms in the second attack were more severe than those of the first. The adenovirus-associated enteritis was mild compared with the illness in both episodes of rotavirus infection.", "contents": "Recurrent attack of rotavirus gastroenteritis after adenovirus-induced diarrhoea. A 14-month-old baby boy suffered a second attack of rotavirus gastroenteritis within one month of the initial one. The second attack followed a diarrhoeal episode associated with adenovirus. Gastrointestinal symptoms in the second attack were more severe than those of the first. The adenovirus-associated enteritis was mild compared with the illness in both episodes of rotavirus infection."}
{"id": "PMID:224827", "title": "[The leukocyte migration inhibition test (LMIT) in recurrent herpes simplex labialis. Comparison of the results of treatment with BCG and Levamisole (author's transl)].", "content": "Forty six patients suffering from recurrent herpes simplex labialis (HSLR) have been treated by either BCG or Levamisole. Therapy was equally successful in both groups: 10 patients remained free of symptoms during the observation period, 11 patients improved clearly and 2 patients did not respond to the therapy. Sensitization of lymphocytes toward herpes simplex virus antigen (HVS-AG) was determined in vitro by means of the leukocyte migration inhibition test (LMIT); test were performed before therapy and in certain intervals after the end of it. While lymphocytes of 10 control persons could be stimulated by HSV-AG, those of patients suffering from HSLR did not react to this antigen before onset of any therapy. Clinical success of therapy correlated well with the in vitro results of the LMIT: after therapy, the lymphocytes of symptom-free and improved patients also reacted in vitro to the antigen added.", "contents": "[The leukocyte migration inhibition test (LMIT) in recurrent herpes simplex labialis. Comparison of the results of treatment with BCG and Levamisole (author's transl)]. Forty six patients suffering from recurrent herpes simplex labialis (HSLR) have been treated by either BCG or Levamisole. Therapy was equally successful in both groups: 10 patients remained free of symptoms during the observation period, 11 patients improved clearly and 2 patients did not respond to the therapy. Sensitization of lymphocytes toward herpes simplex virus antigen (HVS-AG) was determined in vitro by means of the leukocyte migration inhibition test (LMIT); test were performed before therapy and in certain intervals after the end of it. While lymphocytes of 10 control persons could be stimulated by HSV-AG, those of patients suffering from HSLR did not react to this antigen before onset of any therapy. Clinical success of therapy correlated well with the in vitro results of the LMIT: after therapy, the lymphocytes of symptom-free and improved patients also reacted in vitro to the antigen added."}
{"id": "PMID:224830", "title": "Glucocorticoid effects in vitamin D intoxication.", "content": "Calcium balance studies and measurement of 25-hydroxyvitamin D3 (25[OH]D3) levels were performed on a vitamin D intoxicated, hypoparathyroid patient before, during, and after successful management of hypercalcemia with oral prednisone therapy. Prednisone effected a dramatic reduction in both mean serum calcium levels and mean 24-hour urinary calcium excretion within four days on two separate occasions. No changes were apparent in fecal calcium excretion. Calcium balance became less negative with prednisone treatment. Levels of 25(OH) D3 during the same period did not change. Decreased calcium mobilization from bone best accounted for the glucocorticoid-mediated amelioration of hypercalcemia.", "contents": "Glucocorticoid effects in vitamin D intoxication. Calcium balance studies and measurement of 25-hydroxyvitamin D3 (25[OH]D3) levels were performed on a vitamin D intoxicated, hypoparathyroid patient before, during, and after successful management of hypercalcemia with oral prednisone therapy. Prednisone effected a dramatic reduction in both mean serum calcium levels and mean 24-hour urinary calcium excretion within four days on two separate occasions. No changes were apparent in fecal calcium excretion. Calcium balance became less negative with prednisone treatment. Levels of 25(OH) D3 during the same period did not change. Decreased calcium mobilization from bone best accounted for the glucocorticoid-mediated amelioration of hypercalcemia."}
{"id": "PMID:224831", "title": "Day treatment and psychotropic drugs in the aftercare of schizophrenic patients. A Veterans Administration cooperative study.", "content": "Schizophrenic patients referred for day treatment at the time of discharge from ten hospitals were randomly assigned to receive day treatment plus drugs or to receive drugs alone. They were tested before assignment and at 6, 12, 18, and 24 months on social functioning, symptoms, and attitudes. Community tenure and costs were also measured. The ten day centers were described on process variables every six months for the four years of the study. Some centers were found to be effective in treating chronic schizophrenic patients and others were not. All centers improved the patients' social functioning. Six of the centers were found to significantly delay relapse, reduce sumptoms, and change some attitudes. Costs for patients in these centers were not significantly different from the group receiving only drugs. More professional staff hours, group therapy, and a high patient turnover treatment philosophy were associated with poor-result centers. More occupational therapy and a sustained nonthreatening environment were more characteristic of successful outcome centers.", "contents": "Day treatment and psychotropic drugs in the aftercare of schizophrenic patients. A Veterans Administration cooperative study. Schizophrenic patients referred for day treatment at the time of discharge from ten hospitals were randomly assigned to receive day treatment plus drugs or to receive drugs alone. They were tested before assignment and at 6, 12, 18, and 24 months on social functioning, symptoms, and attitudes. Community tenure and costs were also measured. The ten day centers were described on process variables every six months for the four years of the study. Some centers were found to be effective in treating chronic schizophrenic patients and others were not. All centers improved the patients' social functioning. Six of the centers were found to significantly delay relapse, reduce sumptoms, and change some attitudes. Costs for patients in these centers were not significantly different from the group receiving only drugs. More professional staff hours, group therapy, and a high patient turnover treatment philosophy were associated with poor-result centers. More occupational therapy and a sustained nonthreatening environment were more characteristic of successful outcome centers."}
{"id": "PMID:224832", "title": "Substrate oxidation and energy production by Guerin epithelioma mitochondria.", "content": "The mitochondria from Guerin epithelioma and normal rat liver were isolated and their energy production abilities were compared. Both mitochondrial preparations were of the same degree of purity. The percentage of mitochondrial protein in tumour homogenates was three times lower than in rat liver. Guerin epithelioma mitochondria characterized a high respiratory control ratio with succinate and low with NAD dependent substrates in the presence of ADP. The ADP-ATP exchange rate was five times lower in tumour than in rat liver. Energy dependent potassium ions accumulation was about 45% of that found in rat liver mitochondria. The uptake of respiratory substrates was similar in tumour and liver mitochondria. These results indicate on the low efficiency of oxidative phosphorylation in the mitochondria of Guerin epithelioma.", "contents": "Substrate oxidation and energy production by Guerin epithelioma mitochondria. The mitochondria from Guerin epithelioma and normal rat liver were isolated and their energy production abilities were compared. Both mitochondrial preparations were of the same degree of purity. The percentage of mitochondrial protein in tumour homogenates was three times lower than in rat liver. Guerin epithelioma mitochondria characterized a high respiratory control ratio with succinate and low with NAD dependent substrates in the presence of ADP. The ADP-ATP exchange rate was five times lower in tumour than in rat liver. Energy dependent potassium ions accumulation was about 45% of that found in rat liver mitochondria. The uptake of respiratory substrates was similar in tumour and liver mitochondria. These results indicate on the low efficiency of oxidative phosphorylation in the mitochondria of Guerin epithelioma."}
{"id": "PMID:224833", "title": "Influence of ACTH on activity of some granulocytic proteases in patients with multiple sclerosis.", "content": "The effect of treatment with ACTH on activity of granulocytic acid and neutral proteases in patients suffering from multiple sclerosis was studied. Protease activity was distinctly higher in granulocytes from patients. ACTH normalized the activities investigated in patients with exacerbating course multiple sclerosis, but had no influence on hydrolases in the progressive form of the disease.", "contents": "Influence of ACTH on activity of some granulocytic proteases in patients with multiple sclerosis. The effect of treatment with ACTH on activity of granulocytic acid and neutral proteases in patients suffering from multiple sclerosis was studied. Protease activity was distinctly higher in granulocytes from patients. ACTH normalized the activities investigated in patients with exacerbating course multiple sclerosis, but had no influence on hydrolases in the progressive form of the disease."}
{"id": "PMID:224834", "title": "The influence of PGE1 and db-cAMP on permeability of lysosomal membranes of rat lymphocytes in the in vitro histamine test.", "content": "An attempt was made to develop as in vitro model of inflammation which would allow the study of the inflammatory process on the subcellular level and on the influence of PGE1 and db-cAMP on permeability of lysosomal membranes of liver lymphocytes. The results showed that the in vitro histamine test permits evaluation of early changes in the lysosomal membranes. Drugs such as acetylsalicylic acid, hydrocortisone, as well as PGE1 and db-cAMP exerted a stabilizing influence on the lysosomal membranes of rat lymphocytes.", "contents": "The influence of PGE1 and db-cAMP on permeability of lysosomal membranes of rat lymphocytes in the in vitro histamine test. An attempt was made to develop as in vitro model of inflammation which would allow the study of the inflammatory process on the subcellular level and on the influence of PGE1 and db-cAMP on permeability of lysosomal membranes of liver lymphocytes. The results showed that the in vitro histamine test permits evaluation of early changes in the lysosomal membranes. Drugs such as acetylsalicylic acid, hydrocortisone, as well as PGE1 and db-cAMP exerted a stabilizing influence on the lysosomal membranes of rat lymphocytes."}
{"id": "PMID:224835", "title": "Influence of insulin on pharmacokinetics of mannosulfan in rats.", "content": "The purpose of the present study was to investigate the possibilities of potentiation of the antitumor action of mannosulfan after its administration together with insulin. The pharmacokinetics of mannnosulfan were investigated after its administration separately and together with insulin. Concentrations of mannosulfan in the plasma were determined by gas chromatography. Insulin enhanced the rate of absorption of mannosulfan from the peritoneal cavity and prolonged its elimination from the body. It may be assumed that insulin enhances not only passage of mannosulfan from the peritoneal cavity to blood, but also from blood to tissues. Since increased antitumor effectiveness of mannosulfan was accompanied by its decreased toxicity, it may be concluded that insulin causes selective cummulation of the cytostatic only in some tissues, among others, in the tumor.", "contents": "Influence of insulin on pharmacokinetics of mannosulfan in rats. The purpose of the present study was to investigate the possibilities of potentiation of the antitumor action of mannosulfan after its administration together with insulin. The pharmacokinetics of mannnosulfan were investigated after its administration separately and together with insulin. Concentrations of mannosulfan in the plasma were determined by gas chromatography. Insulin enhanced the rate of absorption of mannosulfan from the peritoneal cavity and prolonged its elimination from the body. It may be assumed that insulin enhances not only passage of mannosulfan from the peritoneal cavity to blood, but also from blood to tissues. Since increased antitumor effectiveness of mannosulfan was accompanied by its decreased toxicity, it may be concluded that insulin causes selective cummulation of the cytostatic only in some tissues, among others, in the tumor."}
{"id": "PMID:224837", "title": "Electromyographic value of the tibialis posterior muscle.", "content": "Differentiation between peroneal palsy and L5 radiculopathy poses a diagnostic challenge. However, clinical weakness of the tibialis posterior muscle indicates that the involvement must lie outside the peroneal territory, potentially at a radicular level. Electromyographically this muscle should provide similar information but it has been relatively ignored, possibly for reasons of presumed inaccessibility. A retrospective study was undertaken to delineate the potential electrical discriminatory value of this muscle. Patients selected were those with clinical evidence of lower extremity neurogenic dysfunction in whom needle electrode examination had been performed on the tibialis posterior as well as other posterior and anterior compartment musculature. The parameters measured were the presence of abnormal spontaneous activity suggestive of denervation plus neurogenic motor unit alterations. Abnormalities were detected in the tibialis posterior which were reflected equally in the anterior but not posterior compartment muscles, indicating a shared L5 radicular innervation. Thus this muscle represents a useful source of electrical information assisting in the differentiation between peroneal and radicular dysfunction.", "contents": "Electromyographic value of the tibialis posterior muscle. Differentiation between peroneal palsy and L5 radiculopathy poses a diagnostic challenge. However, clinical weakness of the tibialis posterior muscle indicates that the involvement must lie outside the peroneal territory, potentially at a radicular level. Electromyographically this muscle should provide similar information but it has been relatively ignored, possibly for reasons of presumed inaccessibility. A retrospective study was undertaken to delineate the potential electrical discriminatory value of this muscle. Patients selected were those with clinical evidence of lower extremity neurogenic dysfunction in whom needle electrode examination had been performed on the tibialis posterior as well as other posterior and anterior compartment musculature. The parameters measured were the presence of abnormal spontaneous activity suggestive of denervation plus neurogenic motor unit alterations. Abnormalities were detected in the tibialis posterior which were reflected equally in the anterior but not posterior compartment muscles, indicating a shared L5 radicular innervation. Thus this muscle represents a useful source of electrical information assisting in the differentiation between peroneal and radicular dysfunction."}
{"id": "PMID:224838", "title": "H-reflex latency in uremic neuropathy: correlation with NCV and clinical findings.", "content": "Sixty-two uremic patients on dialysis of varying durations were tested bilaterally for posterior tibial nerve H-reflex latency, at 3-month intervals. Bilateral nerve conduction velocities (NCVs) of the peroneal, tibial, and sural nerves were concomitantly determined in all subjects. Proprioception sense, vibration perception threshold at the great toes, and deep tendon reflexes at the knee and ankle were determined in all subjects on the day of electrodiagnostic testing. The sensitivity of the H-reflex latency in detection of the onset and severity of uremic neuropathy was assessed. H-reflex latency changes were compared to NCV and clinical test results. The following was found: (1) of the parameters studied, the H-reflex latency appeared to be the most sensitive indicator of early uremic polyneuropathies, (2) electrodiagnostic tests were more sensitive to the onset of neuropathies than the clinical testing parameters studied, and (3) the sural sensory nerve appeared to be involved earlier than peroneal and tibial motor nerves in neuropathies studied.", "contents": "H-reflex latency in uremic neuropathy: correlation with NCV and clinical findings. Sixty-two uremic patients on dialysis of varying durations were tested bilaterally for posterior tibial nerve H-reflex latency, at 3-month intervals. Bilateral nerve conduction velocities (NCVs) of the peroneal, tibial, and sural nerves were concomitantly determined in all subjects. Proprioception sense, vibration perception threshold at the great toes, and deep tendon reflexes at the knee and ankle were determined in all subjects on the day of electrodiagnostic testing. The sensitivity of the H-reflex latency in detection of the onset and severity of uremic neuropathy was assessed. H-reflex latency changes were compared to NCV and clinical test results. The following was found: (1) of the parameters studied, the H-reflex latency appeared to be the most sensitive indicator of early uremic polyneuropathies, (2) electrodiagnostic tests were more sensitive to the onset of neuropathies than the clinical testing parameters studied, and (3) the sural sensory nerve appeared to be involved earlier than peroneal and tibial motor nerves in neuropathies studied."}
{"id": "PMID:224836", "title": "[Serologic study of 2 strains of foot-and-mouth virus, cultured in cell line IB-RS-2, clone 26-3].", "content": "The antigenic characteristics of the two FMDV plaque size variants ASQ-PG and ASQ-Pp were studied by serum neutralization kinetics. The results evidentiated that the antiserum ASQ-PG and ASQ-Pp neutralized both variants at the same extent. The plaque population of these variants after passage in laboratory animals was compared in IB-RS-2 cells.", "contents": "[Serologic study of 2 strains of foot-and-mouth virus, cultured in cell line IB-RS-2, clone 26-3]. The antigenic characteristics of the two FMDV plaque size variants ASQ-PG and ASQ-Pp were studied by serum neutralization kinetics. The results evidentiated that the antiserum ASQ-PG and ASQ-Pp neutralized both variants at the same extent. The plaque population of these variants after passage in laboratory animals was compared in IB-RS-2 cells."}
{"id": "PMID:224839", "title": "[Effect of hormones on the susceptibility of the swine cell line IB-RS-2 to foot-and-mouth disease virus].", "content": "The actions of hydrocortisone and insulin on the multiplication of foot-and-mouth disease virus were studied. The data obtained showed that the infectivity and the synthesis of the virus nucleic acid as evaluated through the plaque assay method and the kinetics of Uridine-3H incorporation were increased or decreased by hydrocortisone (2 x 10(-6) M). The induction of both effects seems to be related to the carbohydrate metabolism: when the maintenance medium contained glucose or glucose plus calf serum there was an inhibition on virus multiplication and no effect was observed in the absence of both serum and glucose. This was found both when the hormone was added to the cell culture 24 hours before infection as well as when it was added immediately or thirty minutes after virus adsorption. The possibility that these effects could be related to the synthesis of viral RNA-polimerase is discussed. Insulin (50 ng/ml) did not induce any effect on foot-and-mouth disease virus multiplication. However this hormone antagonized the action of hydrocortisone on the infectivity and on the synthesis of foot-and-mouth disease virus nucleic acid.", "contents": "[Effect of hormones on the susceptibility of the swine cell line IB-RS-2 to foot-and-mouth disease virus]. The actions of hydrocortisone and insulin on the multiplication of foot-and-mouth disease virus were studied. The data obtained showed that the infectivity and the synthesis of the virus nucleic acid as evaluated through the plaque assay method and the kinetics of Uridine-3H incorporation were increased or decreased by hydrocortisone (2 x 10(-6) M). The induction of both effects seems to be related to the carbohydrate metabolism: when the maintenance medium contained glucose or glucose plus calf serum there was an inhibition on virus multiplication and no effect was observed in the absence of both serum and glucose. This was found both when the hormone was added to the cell culture 24 hours before infection as well as when it was added immediately or thirty minutes after virus adsorption. The possibility that these effects could be related to the synthesis of viral RNA-polimerase is discussed. Insulin (50 ng/ml) did not induce any effect on foot-and-mouth disease virus multiplication. However this hormone antagonized the action of hydrocortisone on the infectivity and on the synthesis of foot-and-mouth disease virus nucleic acid."}
{"id": "PMID:224840", "title": "[Isolation and identification of the infectious bovine rhinotracheitis virus in a bovine fetus kidney (IBR/IPV)].", "content": "The authors describe the isolation and identification of a virus from bovine fetal kidney cells maintained in culture for 30 to 45 days. The virus was characterized as a herpesvirus of the infectious bovine rhinotracheitis in cell culture by the evidence of cytopathogenic effect in bovine kidney and testis cultures and serologically by a neutralization test using rabbit anti-infectious bovine rhinotracheitis sera.", "contents": "[Isolation and identification of the infectious bovine rhinotracheitis virus in a bovine fetus kidney (IBR/IPV)]. The authors describe the isolation and identification of a virus from bovine fetal kidney cells maintained in culture for 30 to 45 days. The virus was characterized as a herpesvirus of the infectious bovine rhinotracheitis in cell culture by the evidence of cytopathogenic effect in bovine kidney and testis cultures and serologically by a neutralization test using rabbit anti-infectious bovine rhinotracheitis sera."}
{"id": "PMID:224841", "title": "[Isolation of foot-and mouth disease virus in swine with other diseases].", "content": "The authors took a survey of foot-and-mouth disease samples of myocardium and tonsil from swine which was died without clinicals signs of foot-and-mouth disease, with isolation of virus, type O, A and C. It was observed and accentuated relation between the incidence of hog cholera, pneumonia and atipic foot-and-mouth disease, especially from suckling pigs.", "contents": "[Isolation of foot-and mouth disease virus in swine with other diseases]. The authors took a survey of foot-and-mouth disease samples of myocardium and tonsil from swine which was died without clinicals signs of foot-and-mouth disease, with isolation of virus, type O, A and C. It was observed and accentuated relation between the incidence of hog cholera, pneumonia and atipic foot-and-mouth disease, especially from suckling pigs."}
{"id": "PMID:224842", "title": "[Effects of polyionic compounds in the plaque formation of different strains of foot-and-mouth disease virus (FMDV) in the swine cell line IB-RS-2].", "content": "The effects of dithylaminoethyl (DEAE)-dextran (DD) and dextran-sulfate (DS) were studied in some strains of the foot-and-mouth disease virus (FMDV). The strains ASQ-PG, CR and O, large plaque variants in IB-RS-2 cells, when DD or DS were added to the agar overlay, the plaques were inhibited. However, the strains ASQ-Pp and CI, that are small plaque variants in IB-RS-2 cells, when to the agar overlay was added DD the plaques were greatly enhanced while when was added DS the plaques were inhibited.", "contents": "[Effects of polyionic compounds in the plaque formation of different strains of foot-and-mouth disease virus (FMDV) in the swine cell line IB-RS-2]. The effects of dithylaminoethyl (DEAE)-dextran (DD) and dextran-sulfate (DS) were studied in some strains of the foot-and-mouth disease virus (FMDV). The strains ASQ-PG, CR and O, large plaque variants in IB-RS-2 cells, when DD or DS were added to the agar overlay, the plaques were inhibited. However, the strains ASQ-Pp and CI, that are small plaque variants in IB-RS-2 cells, when to the agar overlay was added DD the plaques were greatly enhanced while when was added DS the plaques were inhibited."}
{"id": "PMID:224846", "title": "A familial mitochondrial myopathy with central defect in neural transmission.", "content": "A family was found to exhibit progressive external ophthalmoplegia, congenital cataracts, variable somatic weakness, gonadal dysgenesis, and, in one member, an abnormal chromosomal pattern. Muscle biopsy specimens showed \"ragged-red\" fibers; electron microscopy showed widespread paracrystalline mitochondrial inclusions. Orbicularis oculi reflex testing in the propositus showed bilateral absence of the late response. The family was evaluated in relation to other familial mitochondrial myopathies; a central defect in brain stem neural transmission was suggested as a mechanism for the progressive external ophthalmoplegia.", "contents": "A familial mitochondrial myopathy with central defect in neural transmission. A family was found to exhibit progressive external ophthalmoplegia, congenital cataracts, variable somatic weakness, gonadal dysgenesis, and, in one member, an abnormal chromosomal pattern. Muscle biopsy specimens showed \"ragged-red\" fibers; electron microscopy showed widespread paracrystalline mitochondrial inclusions. Orbicularis oculi reflex testing in the propositus showed bilateral absence of the late response. The family was evaluated in relation to other familial mitochondrial myopathies; a central defect in brain stem neural transmission was suggested as a mechanism for the progressive external ophthalmoplegia."}
{"id": "PMID:224843", "title": "[Swine cell sublines with different ploidies. III. Susceptibility to foot-and-mouth disease virus].", "content": "IB-RS-10-II subline with tetraploid level cells was more susceptible to the infection by the foot-and-mouth disease virus (FMDV) ASQ-PG strain than IB-RS-10-I subline with diploid level cells, when number and size of plaques and cytopathogenic effect of the virus were used as criteria. Besides, the virus yield in one-cycle of infection was almost the double in IB-RS-10-II than IB-RS-10-I cell subline and the near-tetraploid cells were more susceptible to be infected by the virus than the near-diploid cells. However, in relation to FMDV ASQ-Pp strain the cell subline with a diploid level was more susceptible than that with a tetraploid level. The effects of polyionic compounds under specific experimental conditions were peculiar to each cell subline. 1. Pretreatment of cell monolayers with DEAE-dextran increased the diploid level cells receptivity to the virus, whereas that of the tetraploid level cells was affected only slightly; pretreatment with dextran sulphate did not affect the receptivity of both cell sublines. 2. Pretreatment of the virus with the polycationic compound increased significantly its infectivity to the cells of both sublines; pretreatment of the virus with polyanionic compound decreased significantly its infectivity to the diploid level cells but did not affect that for the tetraploid level cells. 3. Treatment of the agar overlay with the polycationic compound induced increase on the plaque size formed in both cell sublines and treatment with the polyanionic compound inhibited plaque sizes in both cell sublines. A correlation was not found between the susceptibility of both cell sublines to the infection and the chromosomic alterations.", "contents": "[Swine cell sublines with different ploidies. III. Susceptibility to foot-and-mouth disease virus]. IB-RS-10-II subline with tetraploid level cells was more susceptible to the infection by the foot-and-mouth disease virus (FMDV) ASQ-PG strain than IB-RS-10-I subline with diploid level cells, when number and size of plaques and cytopathogenic effect of the virus were used as criteria. Besides, the virus yield in one-cycle of infection was almost the double in IB-RS-10-II than IB-RS-10-I cell subline and the near-tetraploid cells were more susceptible to be infected by the virus than the near-diploid cells. However, in relation to FMDV ASQ-Pp strain the cell subline with a diploid level was more susceptible than that with a tetraploid level. The effects of polyionic compounds under specific experimental conditions were peculiar to each cell subline. 1. Pretreatment of cell monolayers with DEAE-dextran increased the diploid level cells receptivity to the virus, whereas that of the tetraploid level cells was affected only slightly; pretreatment with dextran sulphate did not affect the receptivity of both cell sublines. 2. Pretreatment of the virus with the polycationic compound increased significantly its infectivity to the cells of both sublines; pretreatment of the virus with polyanionic compound decreased significantly its infectivity to the diploid level cells but did not affect that for the tetraploid level cells. 3. Treatment of the agar overlay with the polycationic compound induced increase on the plaque size formed in both cell sublines and treatment with the polyanionic compound inhibited plaque sizes in both cell sublines. A correlation was not found between the susceptibility of both cell sublines to the infection and the chromosomic alterations."}
{"id": "PMID:224847", "title": "Primary aberrant oculomotor regeneration due to intracranial aneurysm.", "content": "Two elderly patients had unilateral ophthalmoparesis and retrobulbar pain. Both had subtle lid signs of aberrant regeneration of the third nerve without proceding acute oculomotor paralysis, and both were found to have intracranial aneurysms. Although primary aberrant oculomotor regeneration has been reported previously in patients with aneurysms and meningiomas, the diagnostic importance of this sign in the elderly has not been emphasized. The presence of lid elevation on downgaze associated with slowly progressive ophthalmoplegia in patients aged 65 or older suggests aneurysm in or near the cavernous sinus.", "contents": "Primary aberrant oculomotor regeneration due to intracranial aneurysm. Two elderly patients had unilateral ophthalmoparesis and retrobulbar pain. Both had subtle lid signs of aberrant regeneration of the third nerve without proceding acute oculomotor paralysis, and both were found to have intracranial aneurysms. Although primary aberrant oculomotor regeneration has been reported previously in patients with aneurysms and meningiomas, the diagnostic importance of this sign in the elderly has not been emphasized. The presence of lid elevation on downgaze associated with slowly progressive ophthalmoplegia in patients aged 65 or older suggests aneurysm in or near the cavernous sinus."}
{"id": "PMID:224844", "title": "[Influence of a hypertonic medium on cell susceptibility to foot-and-mouth disease virus].", "content": "The influence of hypertonic medium on the relationship between two cell clones of IB-RS-2 swine line and the foot-and-mouth disease virus was studied. Although the number of infected cells was increased by the cell treatment with the hypertonic medium, before or during the time of virus adsorption and penetration onto the cells, showed by the plaque number, the viral replication was partially inhibited as showed by the plaque size as by the viral yield in one-cycle of infection. On the other hand, the cell treatment with that medium after virus adsorption and penetration time inhibited as the plaque number and size as the yield of the foot-and-mouth disease virus.", "contents": "[Influence of a hypertonic medium on cell susceptibility to foot-and-mouth disease virus]. The influence of hypertonic medium on the relationship between two cell clones of IB-RS-2 swine line and the foot-and-mouth disease virus was studied. Although the number of infected cells was increased by the cell treatment with the hypertonic medium, before or during the time of virus adsorption and penetration onto the cells, showed by the plaque number, the viral replication was partially inhibited as showed by the plaque size as by the viral yield in one-cycle of infection. On the other hand, the cell treatment with that medium after virus adsorption and penetration time inhibited as the plaque number and size as the yield of the foot-and-mouth disease virus."}
{"id": "PMID:224848", "title": "Topical antibiotic therapy of Pseudomonas aeruginosa keratitis.", "content": "The in vivo antibacterial effectiveness in the rabbit cornea of several commercially available ophthalmic antibiotic preparations was determined against a single strain of Pseudomonas aeruginosa isolated from a human corneal ulcer. Each antibiotic was instilled topically at hourly intervals, and the number of residual viable organisms in the cornea subsequently was ascertained. In vivo measurements correlated well with in vitro data and with generally held clinical impressions. Three antibiotics, gentamicin sulfate, polymyxin B sulfate, and colistin sulfate, suppressed corneal growth of P aeruginosa in commercially available concentrations. Gentamicin was slightly more effective than polymyxin B; both drugs were substantially more effective than colistin. Formulations of gentamicin and polymyxin B containing approximately four times the quantity of drug found in commercial preparations eliminated this P aeruginosa strain from the cornea much more rapidly than did the commercial preparations.", "contents": "Topical antibiotic therapy of Pseudomonas aeruginosa keratitis. The in vivo antibacterial effectiveness in the rabbit cornea of several commercially available ophthalmic antibiotic preparations was determined against a single strain of Pseudomonas aeruginosa isolated from a human corneal ulcer. Each antibiotic was instilled topically at hourly intervals, and the number of residual viable organisms in the cornea subsequently was ascertained. In vivo measurements correlated well with in vitro data and with generally held clinical impressions. Three antibiotics, gentamicin sulfate, polymyxin B sulfate, and colistin sulfate, suppressed corneal growth of P aeruginosa in commercially available concentrations. Gentamicin was slightly more effective than polymyxin B; both drugs were substantially more effective than colistin. Formulations of gentamicin and polymyxin B containing approximately four times the quantity of drug found in commercial preparations eliminated this P aeruginosa strain from the cornea much more rapidly than did the commercial preparations."}
{"id": "PMID:224850", "title": "Vasopressin and isoproterenol activate adenylate cyclase in the guinea pig inner ear.", "content": "Cochleas from guinea pigs were perfused by isotonic buffer after punction of the carotid artery. The cochlea tissue was removed from the bony capsule and separated from the mediolus as band with a sharp needle under the microscope. Cell membranes were prepared subsequently from whole tissue. Purified membranes from the inner ear of guinea pigs contain adenylate cyclase which functionally is coupled with membrane receptors for vasopressin and beta-receptors for isoproterenol (epinephrine), respectively. Both hormones stimulate production of cyclic AMP at 37 degrees C. Furthermore, cyclase activity is increased by addition of Gpp (NH)p, a GTP analog. Possible relationships of these molecular events to cochlear events such as glycogenolysis, ionfluxes, transport and secretion mechanisms, and synaptic transmissions are discussed.", "contents": "Vasopressin and isoproterenol activate adenylate cyclase in the guinea pig inner ear. Cochleas from guinea pigs were perfused by isotonic buffer after punction of the carotid artery. The cochlea tissue was removed from the bony capsule and separated from the mediolus as band with a sharp needle under the microscope. Cell membranes were prepared subsequently from whole tissue. Purified membranes from the inner ear of guinea pigs contain adenylate cyclase which functionally is coupled with membrane receptors for vasopressin and beta-receptors for isoproterenol (epinephrine), respectively. Both hormones stimulate production of cyclic AMP at 37 degrees C. Furthermore, cyclase activity is increased by addition of Gpp (NH)p, a GTP analog. Possible relationships of these molecular events to cochlear events such as glycogenolysis, ionfluxes, transport and secretion mechanisms, and synaptic transmissions are discussed."}
{"id": "PMID:224851", "title": "[Viruses, virus-like and virus-related structures in nasopharyngeal carcinoma (author's transl)].", "content": "Five cases of nasopharyngeal carcinoma with typically elevated EB-virus-antigen-titer were studied by light- and electron microscopic methods. Within the cytoplasm corona viruses in different forms, regular capsid-like particles with a diameter of 60 nm, tubuloreticular aggregates, and pathologic alterations of the membranes of the endoplasmatic reticulum could be found. The nuclei of the tumour cells often showed particles within the nucleoplasm with an average diameter of 100 nm containing a central core; the appearance of the particles is similar to that of herpes viruses as shown in the literature concerning EB-viruses. Atypic mitoses are common as well as free nucleoplasma-like condensates within the ground cytoplasm. Multiple doubling of the membranes of the endoplasmatic reticulum are characteristic for the tumor cell cytoplasm. Myelin figures are often situated within the enlarged tubules of the E. R., within mitochondria and within the nuclei. The results are discussed concerning the possible viral etiology of nasopharyngeal carcinoma. We do not believe that the particles found within the nucleoplasm have a relation to nuclear pores. The arguments are discussed.", "contents": "[Viruses, virus-like and virus-related structures in nasopharyngeal carcinoma (author's transl)]. Five cases of nasopharyngeal carcinoma with typically elevated EB-virus-antigen-titer were studied by light- and electron microscopic methods. Within the cytoplasm corona viruses in different forms, regular capsid-like particles with a diameter of 60 nm, tubuloreticular aggregates, and pathologic alterations of the membranes of the endoplasmatic reticulum could be found. The nuclei of the tumour cells often showed particles within the nucleoplasm with an average diameter of 100 nm containing a central core; the appearance of the particles is similar to that of herpes viruses as shown in the literature concerning EB-viruses. Atypic mitoses are common as well as free nucleoplasma-like condensates within the ground cytoplasm. Multiple doubling of the membranes of the endoplasmatic reticulum are characteristic for the tumor cell cytoplasm. Myelin figures are often situated within the enlarged tubules of the E. R., within mitochondria and within the nuclei. The results are discussed concerning the possible viral etiology of nasopharyngeal carcinoma. We do not believe that the particles found within the nucleoplasm have a relation to nuclear pores. The arguments are discussed."}
{"id": "PMID:224852", "title": "Search for human tumour viruses by transfection: uptake of melanoma and Epstein-Barr virus DNA by human cells.", "content": "In a model system, consistent transfection of chick embryo fibroblasts (CEF) by DNA from the XC cell line occurred, with recovery of infectious Rous sarcoma virus. The techniques were then applied in attempts to recover possible human tumour viruses. Even with various modifications of the XC technique, DNA from three human malignant melanoma cell lines failed to infect adult or foetal human fibroblasts, although melanoma DNA was taken up into nuclei of target cells. XC DNA did not transfect human foetal fibroblasts and melanoma DNA was ineffective in CEF. DNA from the Raji (Epstein-Barr virus non-producer) and QIMR-WIL (producer) lymphoblastoid cell lines did not transfect human cord blood lymphocytes or amnion cells. These broadly applicable techniques therefore failed to recover EB virus, the putative melanoma retrovirus, or other potential tumour virus.", "contents": "Search for human tumour viruses by transfection: uptake of melanoma and Epstein-Barr virus DNA by human cells. In a model system, consistent transfection of chick embryo fibroblasts (CEF) by DNA from the XC cell line occurred, with recovery of infectious Rous sarcoma virus. The techniques were then applied in attempts to recover possible human tumour viruses. Even with various modifications of the XC technique, DNA from three human malignant melanoma cell lines failed to infect adult or foetal human fibroblasts, although melanoma DNA was taken up into nuclei of target cells. XC DNA did not transfect human foetal fibroblasts and melanoma DNA was ineffective in CEF. DNA from the Raji (Epstein-Barr virus non-producer) and QIMR-WIL (producer) lymphoblastoid cell lines did not transfect human cord blood lymphocytes or amnion cells. These broadly applicable techniques therefore failed to recover EB virus, the putative melanoma retrovirus, or other potential tumour virus."}
{"id": "PMID:224853", "title": "The prognosis of breast cancer based on histological assessment.", "content": "Histopathology data from 298 patients with breast cancer have been stored in a computer, and features influencing survival have been analysed by the life table method and presented in survival curves. Prognostic features assessed were the size, type, and grade of neoplasm, the amount of stromal elastosis and lymphocytic infiltrate, and the presence and number of axillary metastases. The most reliable indications of short survival are the presence of axillary metastases and a high tumour grade. These two features are correlated, as high-grade tumours are much more likely to have metastases at presentation. No statistical difference is found in the survival of patients with metastases in one or two axillary nodes compared with those with larger numbers involved. There are differences in survival in different types of carcinoma; the well-differentiated infiltrating duct carcinoma with tubular pattern has the best prognosis, followed by the medullary carcinoma. The size of the tumour has some prognostic significance, but this is outweighed by its grade.", "contents": "The prognosis of breast cancer based on histological assessment. Histopathology data from 298 patients with breast cancer have been stored in a computer, and features influencing survival have been analysed by the life table method and presented in survival curves. Prognostic features assessed were the size, type, and grade of neoplasm, the amount of stromal elastosis and lymphocytic infiltrate, and the presence and number of axillary metastases. The most reliable indications of short survival are the presence of axillary metastases and a high tumour grade. These two features are correlated, as high-grade tumours are much more likely to have metastases at presentation. No statistical difference is found in the survival of patients with metastases in one or two axillary nodes compared with those with larger numbers involved. There are differences in survival in different types of carcinoma; the well-differentiated infiltrating duct carcinoma with tubular pattern has the best prognosis, followed by the medullary carcinoma. The size of the tumour has some prognostic significance, but this is outweighed by its grade."}
{"id": "PMID:224854", "title": "Skin temperature changes in paradoxical sleep in man in the cold.", "content": "Mean skin temperature (Tsk) calculated from seven sites and rectal temperature (Tre) were recorded every minute for a total of 88 man-nights in eight young men sleeping at night in both cold (during the Artic winter) and neutral (laboratory) environments, and were related to the EEG stages of sleep, especially to paradoxical sleep (PS). In the neutral environment, Tre was always above 36 degrees C and Tsk increased during PS. In the cold conditions, during PS, Tsk increased when Tre was high, and decreased when Tre was below 36 degrees C. It was concluded that, although it is not known why a core temperature of about 36 degrees C is the critical point of change in the direction of Tsk variations during PS, the direction in which Tsk will vary during PS is dependent on the core temperature at the time.", "contents": "Skin temperature changes in paradoxical sleep in man in the cold. Mean skin temperature (Tsk) calculated from seven sites and rectal temperature (Tre) were recorded every minute for a total of 88 man-nights in eight young men sleeping at night in both cold (during the Artic winter) and neutral (laboratory) environments, and were related to the EEG stages of sleep, especially to paradoxical sleep (PS). In the neutral environment, Tre was always above 36 degrees C and Tsk increased during PS. In the cold conditions, during PS, Tsk increased when Tre was high, and decreased when Tre was below 36 degrees C. It was concluded that, although it is not known why a core temperature of about 36 degrees C is the critical point of change in the direction of Tsk variations during PS, the direction in which Tsk will vary during PS is dependent on the core temperature at the time."}
{"id": "PMID:224858", "title": "Polymorphonuclear leukocyte-inhibitory factor of Bordetella pertussis. I. Extraction and partial purification of phagocytosis- and chemotaxis-inhibitory activities.", "content": "A new factor that inhibited phagocytosis to opsonized targets and chemotaxis of PMN was extracted from B. pertussis cells, and named PMN-inhibitory factor (PIF). Cells in phase I produced 10 times more PIF than those in phase III, and like other phase I-associated components--the hemagglutinin, the histamine-sensitizing factor and agglutinogens--PIF showed degenerative, phenotypic variation during in vitro culture of phase I bacteria. PIF was partially purified by four steps, including adsorption chromatography on Dansyl-aminononamethylene Sepharose. The resulting fraction was heterogeneous but showed little histamine-sensitizing and cytotoxic activities and was free from LPS, the hemagglutinin and a leukocyte agglutinin. The inherent resistance of B. pertussis cells, in either phase I or III, as demonstrated also in the present study, and PIF-mediated defiance against immunological defense mechanism may constitute a complex host-parasite relation in experimental infections with B. pertussis.", "contents": "Polymorphonuclear leukocyte-inhibitory factor of Bordetella pertussis. I. Extraction and partial purification of phagocytosis- and chemotaxis-inhibitory activities. A new factor that inhibited phagocytosis to opsonized targets and chemotaxis of PMN was extracted from B. pertussis cells, and named PMN-inhibitory factor (PIF). Cells in phase I produced 10 times more PIF than those in phase III, and like other phase I-associated components--the hemagglutinin, the histamine-sensitizing factor and agglutinogens--PIF showed degenerative, phenotypic variation during in vitro culture of phase I bacteria. PIF was partially purified by four steps, including adsorption chromatography on Dansyl-aminononamethylene Sepharose. The resulting fraction was heterogeneous but showed little histamine-sensitizing and cytotoxic activities and was free from LPS, the hemagglutinin and a leukocyte agglutinin. The inherent resistance of B. pertussis cells, in either phase I or III, as demonstrated also in the present study, and PIF-mediated defiance against immunological defense mechanism may constitute a complex host-parasite relation in experimental infections with B. pertussis."}
{"id": "PMID:224859", "title": "The semisynthesis of fragments corresponding to residues 66-104 of horse heart cytochrome c.", "content": "We describe the N epsilon-acetimidylation of horse heart cytochrome c with retention of biological activity, the cleavage of the modified protein by CNBr, the separation of the fragments, and their further side-chain protection. We describe the manipulation of the amino acid sequences of the fragments by stepwise semisynthetic methods. We have prepared fragments corresponding to residues 66-78 and 66-79 of the protein, as well as the [Asp66] analogue of fragment 66-79. We have prepared the natural sequence and the [o-fluoro-Phe82] analogue of the fragment corresponding to residues 81-104 of the protein, and the [N epsilon-trifluoroacetyl-Lys79], the [N epsilon-dinitrophenyl-Lys79] and the [S-acetamidomethyl-Cys79] analogues of fragment 79-104, and the [N epsilon-Cbz-Lys81] analogue of fragment 80-104. We have coupled back the fragments of natural sequence to form a semisynthetic fragment corresponding to residues 66-104 of the protein. Modified fragments were also coupled to give analogues of the 66-104-residue sequence. In every case the homoserine residue representing methionine-80 was removed from the C-terminus of the 66-80-residue fragment and replaced by methionine on the N-terminus of the 81-104 residue fragment during the preparation of the fragments for coupling. The semisynthetic fragments are ready for specific deprotection and further coupling. We have coupled one such fragment to the (1-65)-peptide to produce semisynthetic [Hse65]cytochrome c. The product has satisfactory characteristics on chemical analysis, and on assay of its biological activity.", "contents": "The semisynthesis of fragments corresponding to residues 66-104 of horse heart cytochrome c. We describe the N epsilon-acetimidylation of horse heart cytochrome c with retention of biological activity, the cleavage of the modified protein by CNBr, the separation of the fragments, and their further side-chain protection. We describe the manipulation of the amino acid sequences of the fragments by stepwise semisynthetic methods. We have prepared fragments corresponding to residues 66-78 and 66-79 of the protein, as well as the [Asp66] analogue of fragment 66-79. We have prepared the natural sequence and the [o-fluoro-Phe82] analogue of the fragment corresponding to residues 81-104 of the protein, and the [N epsilon-trifluoroacetyl-Lys79], the [N epsilon-dinitrophenyl-Lys79] and the [S-acetamidomethyl-Cys79] analogues of fragment 79-104, and the [N epsilon-Cbz-Lys81] analogue of fragment 80-104. We have coupled back the fragments of natural sequence to form a semisynthetic fragment corresponding to residues 66-104 of the protein. Modified fragments were also coupled to give analogues of the 66-104-residue sequence. In every case the homoserine residue representing methionine-80 was removed from the C-terminus of the 66-80-residue fragment and replaced by methionine on the N-terminus of the 81-104 residue fragment during the preparation of the fragments for coupling. The semisynthetic fragments are ready for specific deprotection and further coupling. We have coupled one such fragment to the (1-65)-peptide to produce semisynthetic [Hse65]cytochrome c. The product has satisfactory characteristics on chemical analysis, and on assay of its biological activity."}
{"id": "PMID:224860", "title": "Differences in the degradation of native collagen by two microbial collagenases.", "content": "The early stages of degradation of native collagen by two bacterial collagenases were studied by electron microscopy and by automatic Edman degradation. The purified collagenase from Clostridium histolyticum was shown to cleave native collagen at several sites, but not progressively from the N-terminus, as had been previously suggested. The homogeneous collagenase from Achromobacter iophagus cleaves native collagen preferentially at two sites corresponding to the interbands 33-34 and 41-42. The latter lies within the region cleaved by the eukaryotic collagenases.", "contents": "Differences in the degradation of native collagen by two microbial collagenases. The early stages of degradation of native collagen by two bacterial collagenases were studied by electron microscopy and by automatic Edman degradation. The purified collagenase from Clostridium histolyticum was shown to cleave native collagen at several sites, but not progressively from the N-terminus, as had been previously suggested. The homogeneous collagenase from Achromobacter iophagus cleaves native collagen preferentially at two sites corresponding to the interbands 33-34 and 41-42. The latter lies within the region cleaved by the eukaryotic collagenases."}
{"id": "PMID:224861", "title": "Calmodulin and myosin light-chain kinase of rabbit fast skeletal muscle.", "content": "1. It is confirmed that myosin light-chain kinase is a protein of mol.wt. about 80,000 that is inactive in the absence of calmodulin. 2. In the presence of 1 mol of calmodulin/mol of kinase 80-90% of the maximal activity is obtained. 3. Crude preparations of the whole light-chain fraction of rabbit fast-skeletal-muscle myosin contain enough calmodulin to activate the enzyme. A method for the preparation of calmodulin-free P light chain is described. 4. A procedure is described for the isolation of calmodulin from rabbit fast skeletal muscle. 5. Rabbit fast-skeletal-muscle calmodulin is indistinguishable from bovine brain calmodulin in its ability to activate myosin light-chain kinase. The other properties of these two proteins are also very similar. 6. Rabbit fast-skeletal-muscle troponin C was about 10% as effective as calmodulin as activator for myosin light-chain kinase. 7. By chromatography on a Sepharose-calmodulin affinity column evidence was obtained for the formation of a Ca2+-dependent complex between calmodulin and myosin light-chain kinase. 8. Troponin I from rabbit fast skeletal muscle and histone IIAS were phosphorylated by fully activated myosin light-chain kinase at about 1% of the rate of the P light chain.", "contents": "Calmodulin and myosin light-chain kinase of rabbit fast skeletal muscle. 1. It is confirmed that myosin light-chain kinase is a protein of mol.wt. about 80,000 that is inactive in the absence of calmodulin. 2. In the presence of 1 mol of calmodulin/mol of kinase 80-90% of the maximal activity is obtained. 3. Crude preparations of the whole light-chain fraction of rabbit fast-skeletal-muscle myosin contain enough calmodulin to activate the enzyme. A method for the preparation of calmodulin-free P light chain is described. 4. A procedure is described for the isolation of calmodulin from rabbit fast skeletal muscle. 5. Rabbit fast-skeletal-muscle calmodulin is indistinguishable from bovine brain calmodulin in its ability to activate myosin light-chain kinase. The other properties of these two proteins are also very similar. 6. Rabbit fast-skeletal-muscle troponin C was about 10% as effective as calmodulin as activator for myosin light-chain kinase. 7. By chromatography on a Sepharose-calmodulin affinity column evidence was obtained for the formation of a Ca2+-dependent complex between calmodulin and myosin light-chain kinase. 8. Troponin I from rabbit fast skeletal muscle and histone IIAS were phosphorylated by fully activated myosin light-chain kinase at about 1% of the rate of the P light chain."}
{"id": "PMID:224857", "title": "Myocardial extraction of cyclic AMP during pacing-induced angina.", "content": "The application of cyclic AMP as a marker of myocardial ischemia in humans with coronary artery disease has been investigated during pacing-induced angina. Cyclic AMP was determined by a radioimmunoassay. In 15 patients myocardial lactate extraction at rest (20 +/- 12%) converted to production levels (-30 +/- 23%) during angina (p less than 0.0005). Insignificant changes occurred in coronary venous plasma cyclic-AMP levels. The mean myocardial cyclic-AMP extraction at rest (0.3 +/- 8.7%) converted to small release values (-6.0 +/-11%) during angina (= n.s.). No significant correlation was found between myocardial lactate and cyclic-AMP uptake or release. Therefore, cyclic AMP is an insensitive marker in the evaluation of myocardial ischemia.", "contents": "Myocardial extraction of cyclic AMP during pacing-induced angina. The application of cyclic AMP as a marker of myocardial ischemia in humans with coronary artery disease has been investigated during pacing-induced angina. Cyclic AMP was determined by a radioimmunoassay. In 15 patients myocardial lactate extraction at rest (20 +/- 12%) converted to production levels (-30 +/- 23%) during angina (p less than 0.0005). Insignificant changes occurred in coronary venous plasma cyclic-AMP levels. The mean myocardial cyclic-AMP extraction at rest (0.3 +/- 8.7%) converted to small release values (-6.0 +/-11%) during angina (= n.s.). No significant correlation was found between myocardial lactate and cyclic-AMP uptake or release. Therefore, cyclic AMP is an insensitive marker in the evaluation of myocardial ischemia."}
{"id": "PMID:224862", "title": "Enzymes of myo-inositol and inositol lipid metabolism in rats with streptozotocin-induced diabetes.", "content": "Diabetes, with only mild ketosis, was induced in male rats by a single injection of streptozotocin. After 12 weeks the specific activities of enzymes concerned with the metabolism of inositol and of inositol lipids were measured in various tissues. Inositol 1-phosphate synthase (EC 5.5.1.4) was most active in testis and the activity was significantly less in diabetic rats than in controls on a similar diet. Inositol oxygenase (EC 1.13.99.1), which converts myo-inositol into glucuronic acid, was also less active in kidney from diabetic animals. CDP-diacylglycerol-inositol phosphatidyltransferase (EC 2.7.8.11) and phosphatidylinositol 4-phosphate kinase (EC 2.7.1.68) showed decreased specific activities in brain and sciatic nerve of diabetic rats. By contrast the diabetic state did not affect the specific activities of phosphatidylinositol kinase (EC 2.7.1.67) or phosphatidylinositol 4,5-bisphosphate phosphatase (EC 3.1.3.36) in these tissues. The results are discussed in relation to diabetic neuropathy.", "contents": "Enzymes of myo-inositol and inositol lipid metabolism in rats with streptozotocin-induced diabetes. Diabetes, with only mild ketosis, was induced in male rats by a single injection of streptozotocin. After 12 weeks the specific activities of enzymes concerned with the metabolism of inositol and of inositol lipids were measured in various tissues. Inositol 1-phosphate synthase (EC 5.5.1.4) was most active in testis and the activity was significantly less in diabetic rats than in controls on a similar diet. Inositol oxygenase (EC 1.13.99.1), which converts myo-inositol into glucuronic acid, was also less active in kidney from diabetic animals. CDP-diacylglycerol-inositol phosphatidyltransferase (EC 2.7.8.11) and phosphatidylinositol 4-phosphate kinase (EC 2.7.1.68) showed decreased specific activities in brain and sciatic nerve of diabetic rats. By contrast the diabetic state did not affect the specific activities of phosphatidylinositol kinase (EC 2.7.1.67) or phosphatidylinositol 4,5-bisphosphate phosphatase (EC 3.1.3.36) in these tissues. The results are discussed in relation to diabetic neuropathy."}
{"id": "PMID:224863", "title": "Phosphorylation of threonine and serine residues of native and partially dephosphorylated caseins by a rat liver cyclic AMP-insensitive protein kinase.", "content": "The preferential phosphorylation of threonine residues of native casein fractions by a rat liver cyclic AMP-independent protein kinase (EC 2.7.1.37) is abolished by preliminary limited dephosphorylation of the substrates, which promotes a fall in the phosphothreonine/phosphoserine ratios from values higher than 1 to much less than 0.1. This finding and the identification of the threonine residues phosphorylated support the view that the liver protein kinase affects threonine residues only when suitable serine residues, which fulfil the structural requirements for attack by the enzyme but which are not yet phosphorylated, are not available.", "contents": "Phosphorylation of threonine and serine residues of native and partially dephosphorylated caseins by a rat liver cyclic AMP-insensitive protein kinase. The preferential phosphorylation of threonine residues of native casein fractions by a rat liver cyclic AMP-independent protein kinase (EC 2.7.1.37) is abolished by preliminary limited dephosphorylation of the substrates, which promotes a fall in the phosphothreonine/phosphoserine ratios from values higher than 1 to much less than 0.1. This finding and the identification of the threonine residues phosphorylated support the view that the liver protein kinase affects threonine residues only when suitable serine residues, which fulfil the structural requirements for attack by the enzyme but which are not yet phosphorylated, are not available."}
{"id": "PMID:224864", "title": "The cell-wall phosphatase of cotton (Gossypium) is inhibited by kelthane.", "content": "Kelthane [4,4'-dichloro-alpha-(trichloromethyl)benzhydrol] was previously shown to decrease the limited tolerance of susceptible varieties of cotton (Gossypium) to Verticillium wilt. Kelthane was shown in the present study to inhibit the cell-wall p-nitrophenyl phosphatase of cotton. In view of information already establishing the cell wall as a primary site of action of Verticillium wilt, the data are interpreted as suggesting an as yet undefined interaction between Kelthane, cell-wall phosphatase and verticillium-resistance mechanisms of the cell wall.", "contents": "The cell-wall phosphatase of cotton (Gossypium) is inhibited by kelthane. Kelthane [4,4'-dichloro-alpha-(trichloromethyl)benzhydrol] was previously shown to decrease the limited tolerance of susceptible varieties of cotton (Gossypium) to Verticillium wilt. Kelthane was shown in the present study to inhibit the cell-wall p-nitrophenyl phosphatase of cotton. In view of information already establishing the cell wall as a primary site of action of Verticillium wilt, the data are interpreted as suggesting an as yet undefined interaction between Kelthane, cell-wall phosphatase and verticillium-resistance mechanisms of the cell wall."}
{"id": "PMID:224887", "title": "Effect of fluocortin butylester and beclomethasone dipropionate on the adrenal gland in beagle dogs.", "content": "The effect of butyl-6 alpha-fluoro-11 beta-hydroxy-16 alpha-methyl-3,20-dioxo-1,4-pregnadien-21-oate (fluocortin butylester, Vaspit) administered intratracheally and of beclomethasone dipropionate given intratracheally or orally on the adrenal glands of beagle dogs was investigated. The adrenal function was evaluated using a standardized ACTH stimulation test including eosinophil counts 5 h after a single i.v. injection of 0.02mg (approximately 2 IU) ACTH/kg body weight were found as well as the histological and morphometrical examination of the adrenal cortex. The cortisol determination (with Clark's method) 1.5 h and eosinophil counts to be the optimum indices for the evaluation of adrenal function. Beclomethasone dipropionate given intratracheally at daily dose levels of 0.05; 0.1 and 0.5 mg/kg body weight lead to a dose dependent adrenal suppression on the basis of plasma cortisol concentration, eosinophil counts after ACTH stimulation and size of zona fasciculata and reticularis. A complete adrenal suppression was observed at the highest dose level of 0.5 mg/kg bw. Also the oral administration of 0.1 mg/kg bw./day of beclomethasone dipropionate had a definite adrenal suppressive effect comparable to that of 0.1 mg/kg bw. given intratracheally. However, intratracheal administration of fluocortin butylester even after a 320 times higher dose (2 X 8 mg/kg bw./day) had no suppressive effect on the adrenal gland of the beagle dog.", "contents": "Effect of fluocortin butylester and beclomethasone dipropionate on the adrenal gland in beagle dogs. The effect of butyl-6 alpha-fluoro-11 beta-hydroxy-16 alpha-methyl-3,20-dioxo-1,4-pregnadien-21-oate (fluocortin butylester, Vaspit) administered intratracheally and of beclomethasone dipropionate given intratracheally or orally on the adrenal glands of beagle dogs was investigated. The adrenal function was evaluated using a standardized ACTH stimulation test including eosinophil counts 5 h after a single i.v. injection of 0.02mg (approximately 2 IU) ACTH/kg body weight were found as well as the histological and morphometrical examination of the adrenal cortex. The cortisol determination (with Clark's method) 1.5 h and eosinophil counts to be the optimum indices for the evaluation of adrenal function. Beclomethasone dipropionate given intratracheally at daily dose levels of 0.05; 0.1 and 0.5 mg/kg body weight lead to a dose dependent adrenal suppression on the basis of plasma cortisol concentration, eosinophil counts after ACTH stimulation and size of zona fasciculata and reticularis. A complete adrenal suppression was observed at the highest dose level of 0.5 mg/kg bw. Also the oral administration of 0.1 mg/kg bw./day of beclomethasone dipropionate had a definite adrenal suppressive effect comparable to that of 0.1 mg/kg bw. given intratracheally. However, intratracheal administration of fluocortin butylester even after a 320 times higher dose (2 X 8 mg/kg bw./day) had no suppressive effect on the adrenal gland of the beagle dog."}
{"id": "PMID:224888", "title": "[Transplantable experimental tumor. Morphological and ultrastructural study (author's transl].", "content": "An experimental tumor which has been induced in newborn chicken, was transplanted into inbred BALB/c mice and then studied by the means of light and electron microscopy. Sendai virus fusion between MSV-H transformed rat cells and chickembryo cells provided the tumor. Histological pattern of this neoplasia seems to be superposable, both in chicken and in mouse, to that of anaplastic fibrosarcomas and shows some differences from either Rous sarcoma or BALB/c mouse H-6668 spontaneous rabdomyosarcoma patterns. tumor malignancy was evaluated onthe basis of rapid growth", "contents": "[Transplantable experimental tumor. Morphological and ultrastructural study (author's transl]. An experimental tumor which has been induced in newborn chicken, was transplanted into inbred BALB/c mice and then studied by the means of light and electron microscopy. Sendai virus fusion between MSV-H transformed rat cells and chickembryo cells provided the tumor. Histological pattern of this neoplasia seems to be superposable, both in chicken and in mouse, to that of anaplastic fibrosarcomas and shows some differences from either Rous sarcoma or BALB/c mouse H-6668 spontaneous rabdomyosarcoma patterns. tumor malignancy was evaluated onthe basis of rapid growth"}
{"id": "PMID:224889", "title": "Species differences in the activity of a serum triglyceride transferring factor.", "content": "Low density lipoproteins (LDL), endogenously labelled with 3H in the triglyceride moiety, were isolated from rabbit serum and subsequently incubated in vitro at 37 degrees C with unlabelled preparations of rabbit high density lipoproteins (HDL) or very low density lipoproteins (VLDL). In incubations performed in the presence of phosphate buffer, there was no significant transfer of [3H]triglyceride from LDL to either HDL or VLDL; but when rabbit lipoprotein-free serum (the dialysed 1.21 g/ml infranatant) was added, transfer was apparent to both HDL and VLDL. The triglyceride transferring activity of the lipoprotein-free serum was abolished by heating at 85 degrees C for 10 min; all the transferring activity was found in the fraction which precipitated with ammonium sulphate at a concentration of less than 50% saturation. In direct contrast to the rabbit studies, rat serum failed to show a comparable process of triglyceride transfer. In subsequent experiments, mixtures of labelled LDL and unlabelled VLDL isolated either from rabbits or from rats were incubated with lipoprotein-free rabbit, rat or human serum. The lipoprotein-free serum of both the rabbit and man was effective in promoting transfer of 30--50% of LDL [3H]triglyceride into VLDL, regardless of the species origin of the lipoproteins. By contrast the lipoprotein-free serum of rats was only slightly more effective than buffer alone in promoting such transfers. It has been concluded that rabbit and human serum contains a triglyceride transferring factor of far greater activity than that in rat serum.", "contents": "Species differences in the activity of a serum triglyceride transferring factor. Low density lipoproteins (LDL), endogenously labelled with 3H in the triglyceride moiety, were isolated from rabbit serum and subsequently incubated in vitro at 37 degrees C with unlabelled preparations of rabbit high density lipoproteins (HDL) or very low density lipoproteins (VLDL). In incubations performed in the presence of phosphate buffer, there was no significant transfer of [3H]triglyceride from LDL to either HDL or VLDL; but when rabbit lipoprotein-free serum (the dialysed 1.21 g/ml infranatant) was added, transfer was apparent to both HDL and VLDL. The triglyceride transferring activity of the lipoprotein-free serum was abolished by heating at 85 degrees C for 10 min; all the transferring activity was found in the fraction which precipitated with ammonium sulphate at a concentration of less than 50% saturation. In direct contrast to the rabbit studies, rat serum failed to show a comparable process of triglyceride transfer. In subsequent experiments, mixtures of labelled LDL and unlabelled VLDL isolated either from rabbits or from rats were incubated with lipoprotein-free rabbit, rat or human serum. The lipoprotein-free serum of both the rabbit and man was effective in promoting transfer of 30--50% of LDL [3H]triglyceride into VLDL, regardless of the species origin of the lipoproteins. By contrast the lipoprotein-free serum of rats was only slightly more effective than buffer alone in promoting such transfers. It has been concluded that rabbit and human serum contains a triglyceride transferring factor of far greater activity than that in rat serum."}
{"id": "PMID:224890", "title": "Prostacyclin-dependent differences in TXA2 formation by platelets from normal and atherosclerotic rabbits.", "content": "Intact platelets from atherosclerotic rabbits release more thromboxane B2 (TXB2) and 12-hydroxyeicosatetraenoic acid (HETE) than platelets from normal rabbits following incubation with [14C]arachidonic acid (AA). In contrast, no difference is found between homogenates of platelets from normal and atherosclerotic animals. PGI2 stimulates cAMP accumulation and inhibits TXB2 formation more potently in intact platelets from atherosclerotic than from normal rabbits, but has no effect on AA metabolism in homogenised platelets.", "contents": "Prostacyclin-dependent differences in TXA2 formation by platelets from normal and atherosclerotic rabbits. Intact platelets from atherosclerotic rabbits release more thromboxane B2 (TXB2) and 12-hydroxyeicosatetraenoic acid (HETE) than platelets from normal rabbits following incubation with [14C]arachidonic acid (AA). In contrast, no difference is found between homogenates of platelets from normal and atherosclerotic animals. PGI2 stimulates cAMP accumulation and inhibits TXB2 formation more potently in intact platelets from atherosclerotic than from normal rabbits, but has no effect on AA metabolism in homogenised platelets."}
{"id": "PMID:224891", "title": "High density lipoprotein cholesterole levels in peripheral vascular disease and in women on oral contraception.", "content": "Male patients with peripheral vascular disease (PVD) had significantly lower high density lipoprotein cholesterol (HDL-Ch) levels than their corresponding controls, while no significant difference could be demonstrated for female patients with PVD. No significant difference of HDL-Ch was found between women who used oral contraception and those who did not.", "contents": "High density lipoprotein cholesterole levels in peripheral vascular disease and in women on oral contraception. Male patients with peripheral vascular disease (PVD) had significantly lower high density lipoprotein cholesterol (HDL-Ch) levels than their corresponding controls, while no significant difference could be demonstrated for female patients with PVD. No significant difference of HDL-Ch was found between women who used oral contraception and those who did not."}
{"id": "PMID:224892", "title": "[Avoidance learning in rats treated with estrogens].", "content": "Male and female rats were treated with estradiol benzoate in the 5 degrees day of life. The avoidance conditioning, tested after 65 days, was significatively impaired in males treated with estradiol, a significative retardation was observed in females treated, but no significant end-difference versus no-treated females. It is supposed that a hormone induced synaptic shaft/spines ratio in preoptic area may be involved in avoidance conditioning.", "contents": "[Avoidance learning in rats treated with estrogens]. Male and female rats were treated with estradiol benzoate in the 5 degrees day of life. The avoidance conditioning, tested after 65 days, was significatively impaired in males treated with estradiol, a significative retardation was observed in females treated, but no significant end-difference versus no-treated females. It is supposed that a hormone induced synaptic shaft/spines ratio in preoptic area may be involved in avoidance conditioning."}
{"id": "PMID:224894", "title": "A light and electron microscope study on the origin of Fo\u00e0-Kurloff cells.", "content": "Numerous Fo\u00e0-Kurloff (FK) cells have been found in the circulation, spleen, bone marrow, thymus and placenta of guinea pigs under endogenous or exogenous oestrogenic stimulation. The origin of these cells is obscure. In the present experiment, the distribution of FK cells in organs other than those stated above was studied following gonadectomy and hexoestrol administration in guinea pigs of both sexes for either 1 or 10 weeks. More FK cells than those expected from the vascularity of the organ were found in the liver and lungs of male and female animals. The number of FK cells in these organs was larger after the long-term treatment with hexoestrol and it was accompanied by a significant decrease in the number of Kupffer cells of the liver. The latter observation is in contrast to previous reports of increased numbers of Kupffer cells in the liver of oestrogen-receiving mice, a species not producing FK cells. These observations suggest a relation between the two types of cells. No transformation of mature Kupffer cells into FK cells was seen with the electron microscope. However, other findings suggest that both Kupffer cells and FK cells may well be derived from a common precursor of MPS in the bone marrow.", "contents": "A light and electron microscope study on the origin of Fo\u00e0-Kurloff cells. Numerous Fo\u00e0-Kurloff (FK) cells have been found in the circulation, spleen, bone marrow, thymus and placenta of guinea pigs under endogenous or exogenous oestrogenic stimulation. The origin of these cells is obscure. In the present experiment, the distribution of FK cells in organs other than those stated above was studied following gonadectomy and hexoestrol administration in guinea pigs of both sexes for either 1 or 10 weeks. More FK cells than those expected from the vascularity of the organ were found in the liver and lungs of male and female animals. The number of FK cells in these organs was larger after the long-term treatment with hexoestrol and it was accompanied by a significant decrease in the number of Kupffer cells of the liver. The latter observation is in contrast to previous reports of increased numbers of Kupffer cells in the liver of oestrogen-receiving mice, a species not producing FK cells. These observations suggest a relation between the two types of cells. No transformation of mature Kupffer cells into FK cells was seen with the electron microscope. However, other findings suggest that both Kupffer cells and FK cells may well be derived from a common precursor of MPS in the bone marrow."}
{"id": "PMID:224896", "title": "The nature of the effector cells of cell-mediated immune responses to Sendai and Kunz virus infections in mice.", "content": "The development of virus-specific cell-mediated immune (CMI) responses to Sendai and Kunz virus infections of the respiratory tract of mice is described. In addition a heterotypic cell-mediated immune response develops during each of the virus infections. Cell depletion studies indicate that the effector cells of the virus-specific CMI responses are theta antigen bearing T lymphocytes. Similar studies of the heterotypic responses suggest that 2 cell types are involved, T lymphocytes and NK cells.", "contents": "The nature of the effector cells of cell-mediated immune responses to Sendai and Kunz virus infections in mice. The development of virus-specific cell-mediated immune (CMI) responses to Sendai and Kunz virus infections of the respiratory tract of mice is described. In addition a heterotypic cell-mediated immune response develops during each of the virus infections. Cell depletion studies indicate that the effector cells of the virus-specific CMI responses are theta antigen bearing T lymphocytes. Similar studies of the heterotypic responses suggest that 2 cell types are involved, T lymphocytes and NK cells."}
{"id": "PMID:224897", "title": "Proliferative epidermis of essential fatty acid deficient mice has reduced cyclic AMP content.", "content": "We have simultaneously measured epidermal DNA synthesis, epidermal thickness and cyclic nucleotide levels in essential fatty acid (EFA) deficient hairless mice skin. In vitro epidermal DNA synthesis and epidermal thickness were significantly increased in EFA deficient epidermis. Cyclic AMP levels were significantly reduced when expressed using three different data bases. Cyclic GMP levels were increased using two data bases but these increases were not statistically significant; Cyclic AMP/cyclic GMP ratios were significantly decreased in the EFA deficient skin. The results provide evidence that cyclic nucleotide levels are altered in an animal model of benign epidermal proliferation.", "contents": "Proliferative epidermis of essential fatty acid deficient mice has reduced cyclic AMP content. We have simultaneously measured epidermal DNA synthesis, epidermal thickness and cyclic nucleotide levels in essential fatty acid (EFA) deficient hairless mice skin. In vitro epidermal DNA synthesis and epidermal thickness were significantly increased in EFA deficient epidermis. Cyclic AMP levels were significantly reduced when expressed using three different data bases. Cyclic GMP levels were increased using two data bases but these increases were not statistically significant; Cyclic AMP/cyclic GMP ratios were significantly decreased in the EFA deficient skin. The results provide evidence that cyclic nucleotide levels are altered in an animal model of benign epidermal proliferation."}
{"id": "PMID:224898", "title": "Modulation of transferrin receptors in bone marrow cells by changes in lipid fluidity.", "content": "The hypothesis that modulation of transferrin receptors during haematopoiesis is mediated by changes in the lipid fluidity of the cell membranes was tested in this study with bone marrow cells. Binding conditions were first established, under which internalization of fluorescently-labelled transferrin was reduced to a minimum during the binding assays. Cholesterol depletion, which was achieved by a mild physiological treatment, and which increased the membrane-lipid fluidity, resulted in a substantial increase in the average number of the available transferrin receptors per bone marrow cell. Cholesterol enrichment mediated a converse effect. These findings correlate well with the changes observed in the availability of transferrin receptors and membrane microviscosity during differentiation of erythroid cells. In line with the notion of passive modulation, it is proposed that the transferrin receptor is a cross-membrane protein with a substantial portion facing the cytoplasm.", "contents": "Modulation of transferrin receptors in bone marrow cells by changes in lipid fluidity. The hypothesis that modulation of transferrin receptors during haematopoiesis is mediated by changes in the lipid fluidity of the cell membranes was tested in this study with bone marrow cells. Binding conditions were first established, under which internalization of fluorescently-labelled transferrin was reduced to a minimum during the binding assays. Cholesterol depletion, which was achieved by a mild physiological treatment, and which increased the membrane-lipid fluidity, resulted in a substantial increase in the average number of the available transferrin receptors per bone marrow cell. Cholesterol enrichment mediated a converse effect. These findings correlate well with the changes observed in the availability of transferrin receptors and membrane microviscosity during differentiation of erythroid cells. In line with the notion of passive modulation, it is proposed that the transferrin receptor is a cross-membrane protein with a substantial portion facing the cytoplasm."}
{"id": "PMID:224899", "title": "Sex hormone binding globulin capacity and postmenopausal hormone replacement therapy.", "content": "The sex hormone binding globulin (SHBG) capacity was measured in 26 normal untreated postmenopausal women and 10 postmenopausal women taking different types of hormone replacement therapy. The patients on hormone replacement therapy had significantly higher levels of SHBG than postmenopausal women (p less than 0.001) and also significantly higher levels than 52 normal ovulating women studied previously (Pogmore and Jequier, 1979; p less than 0.02). This suggests that postmenopausal women on hormone therapy are being overtreated.", "contents": "Sex hormone binding globulin capacity and postmenopausal hormone replacement therapy. The sex hormone binding globulin (SHBG) capacity was measured in 26 normal untreated postmenopausal women and 10 postmenopausal women taking different types of hormone replacement therapy. The patients on hormone replacement therapy had significantly higher levels of SHBG than postmenopausal women (p less than 0.001) and also significantly higher levels than 52 normal ovulating women studied previously (Pogmore and Jequier, 1979; p less than 0.02). This suggests that postmenopausal women on hormone therapy are being overtreated."}
{"id": "PMID:224900", "title": "Tumours of the salivary glands: a histological and clinical review.", "content": "The aim of this paper is to try to identify points of correlation between the histological appearance and the clinical behaviour of minor salivary gland tumours. To this end 62 well-documented minor salivary gland tumours have been followed up for at least five years or until recurrence. The discussion is limited to the adenoidcystic carcinoma, the pleomorphic adenoma and the basal cell adenoma, since only these three tumours were represented in sufficient numbers to be analysed. For each tumour a number of histological pointers to prognosis are reviewed. In the case of the basal cell adenoma, a recently recognised tumour, the possibility of confusion with the adenoidcystic carcinoma is discussed.", "contents": "Tumours of the salivary glands: a histological and clinical review. The aim of this paper is to try to identify points of correlation between the histological appearance and the clinical behaviour of minor salivary gland tumours. To this end 62 well-documented minor salivary gland tumours have been followed up for at least five years or until recurrence. The discussion is limited to the adenoidcystic carcinoma, the pleomorphic adenoma and the basal cell adenoma, since only these three tumours were represented in sufficient numbers to be analysed. For each tumour a number of histological pointers to prognosis are reviewed. In the case of the basal cell adenoma, a recently recognised tumour, the possibility of confusion with the adenoidcystic carcinoma is discussed."}
{"id": "PMID:224902", "title": "Chorismate mutase-prephenate dehydrogenase from Aerobacter aerogenes: evidence that the two reactions occur at one active site.", "content": "The relationship between the sites for catalysis of two reactions by the bifunctional enzyme chorismate mutase--prephenate dehydrogenase has been investigated. The results are consistent with the occurrence of both reactions at one active site. Comparisons have been made between experimental data for the time course of the overall reaction and computer simulations, according to various models for the relationship between the mutase and dehydrogenase sites. A model based on a single active site is consistent with the time course data if a minor proportion of the chorismate that reacts can be converted through to (hydroxyphenyl)pyruvate without the intermediate release of prephenate. Consistent with this requirement, some channeling of radioactivity from chorismate to (hydroxyphenyl)pyruvate has been detected. A model based on two separate sites has also been considered; the simulations show that if this model applies there is no need to postulate any channeling of the intermediate, prephenate, between the sites and there must be marked inhibition of the dehydrogenase reaction by chorismate. Since channeling has been observed and chorismate increases the dehydrogenase rate under all conditions, the two-site model appears unlikely. Consistent with the one-site model are the observations that a variety of inactivating conditions cause parallel loss of mutase and dehydrogenase activity and that identical protection against inactivation of both mutase and dehydrogenase by iodoacetamide is afforded by prephenate.", "contents": "Chorismate mutase-prephenate dehydrogenase from Aerobacter aerogenes: evidence that the two reactions occur at one active site. The relationship between the sites for catalysis of two reactions by the bifunctional enzyme chorismate mutase--prephenate dehydrogenase has been investigated. The results are consistent with the occurrence of both reactions at one active site. Comparisons have been made between experimental data for the time course of the overall reaction and computer simulations, according to various models for the relationship between the mutase and dehydrogenase sites. A model based on a single active site is consistent with the time course data if a minor proportion of the chorismate that reacts can be converted through to (hydroxyphenyl)pyruvate without the intermediate release of prephenate. Consistent with this requirement, some channeling of radioactivity from chorismate to (hydroxyphenyl)pyruvate has been detected. A model based on two separate sites has also been considered; the simulations show that if this model applies there is no need to postulate any channeling of the intermediate, prephenate, between the sites and there must be marked inhibition of the dehydrogenase reaction by chorismate. Since channeling has been observed and chorismate increases the dehydrogenase rate under all conditions, the two-site model appears unlikely. Consistent with the one-site model are the observations that a variety of inactivating conditions cause parallel loss of mutase and dehydrogenase activity and that identical protection against inactivation of both mutase and dehydrogenase by iodoacetamide is afforded by prephenate."}
{"id": "PMID:224903", "title": "Proton nuclear magnetic resonance study of the conformation and configuration of the cyclized pyridine nucleotide adducts.", "content": "We have closely examined by high-frequenty 1H nuclear magnetic resonance spectroscopy the structure of the adducts which form when various carbonyl compounds react with pyridine nucleotides at elevated pH. These studies show that the adducts of N-(2,6-dichlorobenzyl)nicotinamide-acetone, n-(2,6-dichlorobenzyl)nicotinamide-pyruvate, NMN-pyruvate, NAD-pyruvate, NAD-acetaldehyde, and NAD-oxaloacetate form with identical structural features as well as configuration. The following structural features are observed: (1) the adducts are pyridine N-4-substituted compounds; (2) a second six-membered ring forms by addition of the nicotinamide amido to the carbonyl group of the compound forming the addition complex; (3) cyclization occurs stereospecifically, indicating that the stereochemistry is predetermined by the initial attack at the N-4 position; (4) two diastereomeric forms are observed for each nucleotide adduct. Finally, the determination of configuration at all symmetric carbon atoms in these adducts will be discussed.", "contents": "Proton nuclear magnetic resonance study of the conformation and configuration of the cyclized pyridine nucleotide adducts. We have closely examined by high-frequenty 1H nuclear magnetic resonance spectroscopy the structure of the adducts which form when various carbonyl compounds react with pyridine nucleotides at elevated pH. These studies show that the adducts of N-(2,6-dichlorobenzyl)nicotinamide-acetone, n-(2,6-dichlorobenzyl)nicotinamide-pyruvate, NMN-pyruvate, NAD-pyruvate, NAD-acetaldehyde, and NAD-oxaloacetate form with identical structural features as well as configuration. The following structural features are observed: (1) the adducts are pyridine N-4-substituted compounds; (2) a second six-membered ring forms by addition of the nicotinamide amido to the carbonyl group of the compound forming the addition complex; (3) cyclization occurs stereospecifically, indicating that the stereochemistry is predetermined by the initial attack at the N-4 position; (4) two diastereomeric forms are observed for each nucleotide adduct. Finally, the determination of configuration at all symmetric carbon atoms in these adducts will be discussed."}
{"id": "PMID:224904", "title": "Cross-linking of iodine-125-labeled, calcium-dependent regulatory protein to the Ca2+-sensitive phosphodiesterase purified from bovine heart.", "content": "The calcium-dependent regulatory protein (CDR).Ca2+ sensitive cyclic nucleotide phosphodiesterase was purified to apparent homogeneity from bovine heart by using ammonium sulfate fractionation, DEAE-ceelulose chromatography, and CDR-Sepharose affinity chromatography. The enzyme was purifed 13 750-fold with a 10% yield and a specific activity of 275 mumol of cAMP min-1 mg-1. The purified enzyme ran as a single band during sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an apparent molecular weight of 57 000. Phosphodiesterase activity was stimulated 10-fold by Ca2+ and CDR with half-maximal activation occurring at 9 ng/assay. [125I]CDR was cross-linked to the purified phosphodiesterase by using dimethyl suberimidate Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the cross-linked products revealed a number of discrete 125I-labeled bands. The molecular weights of the cross-linked products indicate that the stoichiometry of the phosphodiesterase complex is A2C2, where A is the phosphodiesterase catalytic subunit and C is the calcium-dependent regulatory protein.", "contents": "Cross-linking of iodine-125-labeled, calcium-dependent regulatory protein to the Ca2+-sensitive phosphodiesterase purified from bovine heart. The calcium-dependent regulatory protein (CDR).Ca2+ sensitive cyclic nucleotide phosphodiesterase was purified to apparent homogeneity from bovine heart by using ammonium sulfate fractionation, DEAE-ceelulose chromatography, and CDR-Sepharose affinity chromatography. The enzyme was purifed 13 750-fold with a 10% yield and a specific activity of 275 mumol of cAMP min-1 mg-1. The purified enzyme ran as a single band during sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an apparent molecular weight of 57 000. Phosphodiesterase activity was stimulated 10-fold by Ca2+ and CDR with half-maximal activation occurring at 9 ng/assay. [125I]CDR was cross-linked to the purified phosphodiesterase by using dimethyl suberimidate Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the cross-linked products revealed a number of discrete 125I-labeled bands. The molecular weights of the cross-linked products indicate that the stoichiometry of the phosphodiesterase complex is A2C2, where A is the phosphodiesterase catalytic subunit and C is the calcium-dependent regulatory protein."}
{"id": "PMID:224905", "title": "Stereochemical course of the reaction catalyzed by 5'-nucleotide phosphodiesterase from snake venom.", "content": "The hydrolysis reaction of ATP alpha S by snake venom phosphodiesterase is highly specific for the B diastereomer and proceeds with 88% retention of configuration at phosphorus. Since this enzyme also catalyzes the hydrolysis of the S enantimoer of O-p-nitrophenyl phenylphosphonothioate, the absolute configuration at A alpha of ATP alpha S (B) is assigned as the R configuration provided the two substrates are processed identically. A mechanism for the hydrolysis reactions catalzyed by the venom phosphodiesterase involving at least a single covalent phosphoryl-enzyme intermediate is in accord with this result.", "contents": "Stereochemical course of the reaction catalyzed by 5'-nucleotide phosphodiesterase from snake venom. The hydrolysis reaction of ATP alpha S by snake venom phosphodiesterase is highly specific for the B diastereomer and proceeds with 88% retention of configuration at phosphorus. Since this enzyme also catalyzes the hydrolysis of the S enantimoer of O-p-nitrophenyl phenylphosphonothioate, the absolute configuration at A alpha of ATP alpha S (B) is assigned as the R configuration provided the two substrates are processed identically. A mechanism for the hydrolysis reactions catalzyed by the venom phosphodiesterase involving at least a single covalent phosphoryl-enzyme intermediate is in accord with this result."}
{"id": "PMID:224906", "title": "Magnesium ion dependent rabbit skeletal muscle myosin guanosine and thioguanosine triphosphatase mechanism and a novel guanosine diphosphatase reaction.", "content": "The mechanism of the Mg2+-dependent myosin subfragment 1 catalyzed hydrolysis of GTP and 2-amino-6-mercapto-9-beta-ribofuranosylpurine 5'-triphosphate (thioGTP) has been investigated by rapid-reaction techniques. The myosin was isolated from rabbit skeletal muscle. The steady-state intermediate of these reactions consists pre-dominantly of a protein-substrate complex unlike the myosin subfragment 1 ATPase reaction which has a protein-products complex as the principal steady-state component. The mechanism of GTP hydrolysis catalyzed by subfragment 1 has other marked differences from the ATPase mechanism. The second-order rate constant of binding of GTP to subfragment 1 is tenfold greater than that for GDP binding. The dissociation rate constant of GDP from subfragment 1 is 0.06 s-1 compared with the subfragment 1 catalytic center activity for GTP hydrolysis of 0.5 s-1 at pH 8.0 and 20 degrees C. This shows that GDP bound to subfragment 1 forms a complex which is not kinetically competent to be an intermediate of the GTPase mechanism. GDP is hydrolyzed in the presence of subfragment 1 to GMP and Pi. The subfragment 1 GTPase mechanism has a nuber if features in common with that of the elongation factor Tu GTPase of the protein biosynthetic system of Escherichia coli.", "contents": "Magnesium ion dependent rabbit skeletal muscle myosin guanosine and thioguanosine triphosphatase mechanism and a novel guanosine diphosphatase reaction. The mechanism of the Mg2+-dependent myosin subfragment 1 catalyzed hydrolysis of GTP and 2-amino-6-mercapto-9-beta-ribofuranosylpurine 5'-triphosphate (thioGTP) has been investigated by rapid-reaction techniques. The myosin was isolated from rabbit skeletal muscle. The steady-state intermediate of these reactions consists pre-dominantly of a protein-substrate complex unlike the myosin subfragment 1 ATPase reaction which has a protein-products complex as the principal steady-state component. The mechanism of GTP hydrolysis catalyzed by subfragment 1 has other marked differences from the ATPase mechanism. The second-order rate constant of binding of GTP to subfragment 1 is tenfold greater than that for GDP binding. The dissociation rate constant of GDP from subfragment 1 is 0.06 s-1 compared with the subfragment 1 catalytic center activity for GTP hydrolysis of 0.5 s-1 at pH 8.0 and 20 degrees C. This shows that GDP bound to subfragment 1 forms a complex which is not kinetically competent to be an intermediate of the GTPase mechanism. GDP is hydrolyzed in the presence of subfragment 1 to GMP and Pi. The subfragment 1 GTPase mechanism has a nuber if features in common with that of the elongation factor Tu GTPase of the protein biosynthetic system of Escherichia coli."}
{"id": "PMID:224908", "title": "Allosteric cooperative interactions among redox sites of Pseudomonas cytochrome oxidase.", "content": "Anaerobic reductive spectrophotometric titrations of Pseudomonas aeruginosa cytochrome oxidase were performed. Both types of hemes (C and D) of the dimeric enzyme were monitored. The reduction process was found to involve cooperative allosteric and spectroscopic interactions between the two subunits. The model fitting the data best involves the following features. (1) The redox potential of heme C is about 60 mV higher than that of heme D. (2) In the electron uptake, a positive cooperativity of about 30 mV exists between the two D-type hemes residing in the two subunits. (3) A negative cooperativity of the same magnitude (30 mV) is found between the two C-type hemes bound to two subunits. (4) No interaction was found between heme C and D in the same subunit or in the different subunits. (5) It is suggested that the reduction of the heme, of each kind, has about twice the spectral change compared to that observed upon reduction of the second one. The possible significance of this model for the mechanism of action of the enzyme is discussed", "contents": "Allosteric cooperative interactions among redox sites of Pseudomonas cytochrome oxidase. Anaerobic reductive spectrophotometric titrations of Pseudomonas aeruginosa cytochrome oxidase were performed. Both types of hemes (C and D) of the dimeric enzyme were monitored. The reduction process was found to involve cooperative allosteric and spectroscopic interactions between the two subunits. The model fitting the data best involves the following features. (1) The redox potential of heme C is about 60 mV higher than that of heme D. (2) In the electron uptake, a positive cooperativity of about 30 mV exists between the two D-type hemes residing in the two subunits. (3) A negative cooperativity of the same magnitude (30 mV) is found between the two C-type hemes bound to two subunits. (4) No interaction was found between heme C and D in the same subunit or in the different subunits. (5) It is suggested that the reduction of the heme, of each kind, has about twice the spectral change compared to that observed upon reduction of the second one. The possible significance of this model for the mechanism of action of the enzyme is discussed"}
{"id": "PMID:224909", "title": "Influence of temperature and cholesterol on the rotational diffusion of band 3 in the human erythrocyte membrane.", "content": "Band 3 rotation in the human erythrocyte membrane is measured by observing flash-induced dichroism of eosin probes. The decay of the absorption anisotropy is found to be strongly dependent on temperature. The results are analyzed on the assumption that rotation of band 3 only occurs about the membrane normal. It is deduced that both fast and slowly rotating forms of band 3 coexist in the membrane. The equilibrium between these forms is temperature dependent, the slowly rotating species becoming increasingly dominant as the temperature is reduced. Plots of the fractional distribution of the different species against temperature show a marked change of slope at around 37--40 degrees C. The effects are essentially reversible over the range 1--45 degrees C and independent of the presence of the spectrin--actin network. The results could be due to temperature-dependent protein--protein associations mediated either by a protein conformational change or by lipid phase segregation. In further experiments, the cholesterol content of the erythrocyte membrane is varied by incubation with lipid vesicles. No significant changes in the rotational diffusion of band 3 are observed following variation of membrane cholesterol/phospholipid mole ratios over the range 0.34--1.66. This is a surprising result in view of the well-known effects of cholesterol on lipid fluidity.", "contents": "Influence of temperature and cholesterol on the rotational diffusion of band 3 in the human erythrocyte membrane. Band 3 rotation in the human erythrocyte membrane is measured by observing flash-induced dichroism of eosin probes. The decay of the absorption anisotropy is found to be strongly dependent on temperature. The results are analyzed on the assumption that rotation of band 3 only occurs about the membrane normal. It is deduced that both fast and slowly rotating forms of band 3 coexist in the membrane. The equilibrium between these forms is temperature dependent, the slowly rotating species becoming increasingly dominant as the temperature is reduced. Plots of the fractional distribution of the different species against temperature show a marked change of slope at around 37--40 degrees C. The effects are essentially reversible over the range 1--45 degrees C and independent of the presence of the spectrin--actin network. The results could be due to temperature-dependent protein--protein associations mediated either by a protein conformational change or by lipid phase segregation. In further experiments, the cholesterol content of the erythrocyte membrane is varied by incubation with lipid vesicles. No significant changes in the rotational diffusion of band 3 are observed following variation of membrane cholesterol/phospholipid mole ratios over the range 0.34--1.66. This is a surprising result in view of the well-known effects of cholesterol on lipid fluidity."}
{"id": "PMID:224910", "title": "Microsecond luminescence emission from copper cytochrome c.", "content": "The luminescence of Cu-substituted cytochrome c exhibits temperature-dependent decay modes and spectral shifts at temperatures below 80 K. By comparison with the data from metal-substituted porphyrins, we determined intramolecular rate parameters. The observed tripdoublet decay time is 13 +/- 1 mus at 77 K and the quartet decay time is 12 +/- 5 mus below 30 K. We also investigated the luminescence emission from Cu cytochrome c in the presence of cytochrome c depleted mitochondria and in the presence of soluble cytochrome c oxidase; upon binding, the intensity and decay time of the emission are altered. The results indicate an interaction between cytochrome c and its mitochondrial binding site which depends on the electronic state of cytochrome c.", "contents": "Microsecond luminescence emission from copper cytochrome c. The luminescence of Cu-substituted cytochrome c exhibits temperature-dependent decay modes and spectral shifts at temperatures below 80 K. By comparison with the data from metal-substituted porphyrins, we determined intramolecular rate parameters. The observed tripdoublet decay time is 13 +/- 1 mus at 77 K and the quartet decay time is 12 +/- 5 mus below 30 K. We also investigated the luminescence emission from Cu cytochrome c in the presence of cytochrome c depleted mitochondria and in the presence of soluble cytochrome c oxidase; upon binding, the intensity and decay time of the emission are altered. The results indicate an interaction between cytochrome c and its mitochondrial binding site which depends on the electronic state of cytochrome c."}
{"id": "PMID:224914", "title": "Binding of reduced and oxidized nicotinamide adenine dinucleotide to pig heart supernatant malate dehydrogenase.", "content": "The association reactions of NADH and NAD+ with dimeric pig heart supernatant malate dehydrogenase (s-MDH) have been measured at pH 6 and 8 by calorimetric and fluorescence methods, and the thermodynamic parameters describing these reactions have been evaluated. Coenzyme binding is associated with the uptake of 0.55 mol of H+/mol of NADH at pH 8 and 0.19 mol of H+ at pH 6. No significant effect of NAD+ binding on proton binding was observed. Increase in ionic strength strongly affects the free energies of binding of NAD+ and NADH. No cooperativity was observed in the enthalpy or free energy changes for binding of NAD+ or NADH. The differences in free energy of binding of NAD+ and NADH and the effect of pH on binding of NADH are entropy based. These effects are interpreted as reflecting a small number of interactions within the active site that are predominantly ionic.", "contents": "Binding of reduced and oxidized nicotinamide adenine dinucleotide to pig heart supernatant malate dehydrogenase. The association reactions of NADH and NAD+ with dimeric pig heart supernatant malate dehydrogenase (s-MDH) have been measured at pH 6 and 8 by calorimetric and fluorescence methods, and the thermodynamic parameters describing these reactions have been evaluated. Coenzyme binding is associated with the uptake of 0.55 mol of H+/mol of NADH at pH 8 and 0.19 mol of H+ at pH 6. No significant effect of NAD+ binding on proton binding was observed. Increase in ionic strength strongly affects the free energies of binding of NAD+ and NADH. No cooperativity was observed in the enthalpy or free energy changes for binding of NAD+ or NADH. The differences in free energy of binding of NAD+ and NADH and the effect of pH on binding of NADH are entropy based. These effects are interpreted as reflecting a small number of interactions within the active site that are predominantly ionic."}
{"id": "PMID:224915", "title": "Purification and subunit structure of nicotinamide adenine dinucleotide specific isocitrate dehydrogenase from Neurospora crassa.", "content": "Neurospora crassa nicotinamide adenine dinucleotide specific isocitrate dehydrogenase (EC 1.1.1.41) has been purified to homogeneity by the criteria of disc gel electrophoresis and sedimentation equilibrium. Purification of the enzyme is facilitated by the presence of phenylmethanesulfonyl fluoride and by the use of a ribose-linked adenosine 5'-monophosphate affinity column. The enzyme appears to be composed of nonidentical subunits of molecular weights 42 800 and 38 300 as estimated by polyacrylamide gel electrophoresis in 0.1% sodium dodecyl sulfate. From the intensity of each band and the native molecular weight, it is concluded that the enzyme is composed of either six or eight subunits, three or four of each type, respectively. The availability of pure enzyme will allow clarification of the structure of the enzyme by ligand binding studies.", "contents": "Purification and subunit structure of nicotinamide adenine dinucleotide specific isocitrate dehydrogenase from Neurospora crassa. Neurospora crassa nicotinamide adenine dinucleotide specific isocitrate dehydrogenase (EC 1.1.1.41) has been purified to homogeneity by the criteria of disc gel electrophoresis and sedimentation equilibrium. Purification of the enzyme is facilitated by the presence of phenylmethanesulfonyl fluoride and by the use of a ribose-linked adenosine 5'-monophosphate affinity column. The enzyme appears to be composed of nonidentical subunits of molecular weights 42 800 and 38 300 as estimated by polyacrylamide gel electrophoresis in 0.1% sodium dodecyl sulfate. From the intensity of each band and the native molecular weight, it is concluded that the enzyme is composed of either six or eight subunits, three or four of each type, respectively. The availability of pure enzyme will allow clarification of the structure of the enzyme by ligand binding studies."}
{"id": "PMID:224916", "title": "Mechanism of phenylalanyl-tRNA synthetase of Escherichia coli K. 10. Modulation of catalytic properties by magnesium.", "content": "The association of phenylalanylptRNA and Mg2+ follows a biphasic concentration dependence as indicated by the active site directed fluorescent indicator 2-p-toluidinyl-naphthalene-6-sulfonate. The macroscopic dissociation constants are 0.16 +/- 0.03 and 4.1 +/- mM. The effect of Mg2+ on the association of enzyme and MgATP, on the synergistic binding of MgATP and L-phenylalaninol, and on the pre-steady-state synthesis and pyrophosphorolysis of the enzyme-phenylalanyladenylate complex in the absence and the presence of tRNA Phe has been measured by established equilibrium and stopped-flow techniques using 2-p-toluidinylnaphthalene-6-sulfonate. At 10 mM Mg2+, the association of enzyme and MgATP is biphasic with dissociation constants of 0.25 +/- 0.03 and 9.1 +/- 1.7 mM. At 2 mM Mg2+, a single dissociation constant of 5.0 +/- 0.5 mM is indicated. The coupling constant of the synergistic reaction is 15 at 1 mM Mg2+ and 290 at 10 mM Mg2+. The Hill constant of the sigmoidal dependence is 3.6. The strengthening of the synergism is believed to reflect a Mg2+-dependent coupling of the synergistic reactions at the two active sites of the enzyme, the coupling being negligible at 1 mM and maximal at 10 mM Mg2+. The pre-steady-state rate of adenylate synthesis is accelerated by the presence of Mg2+. The effect is to decrease the value of the Michaelis-Menten constant of MgATP. Another effect is to increase the rate constant when tRNA Phe is present. At subsaturating [MgATP], the [Mg2+] dependence of the observed rate constant is hyperbolical in the absence and sigmoidal (Hill constant, 3.5) in the presence of tRNA Phe. The rate of the pyrophosphorolysis is enhanced by a decrease of the Michaelis-Menten constant of MgPPi. The effects on the thermodynamics and kinetics parallel the occupancy of the low-affinity Mg2+-binding sites of the enzyme.", "contents": "Mechanism of phenylalanyl-tRNA synthetase of Escherichia coli K. 10. Modulation of catalytic properties by magnesium. The association of phenylalanylptRNA and Mg2+ follows a biphasic concentration dependence as indicated by the active site directed fluorescent indicator 2-p-toluidinyl-naphthalene-6-sulfonate. The macroscopic dissociation constants are 0.16 +/- 0.03 and 4.1 +/- mM. The effect of Mg2+ on the association of enzyme and MgATP, on the synergistic binding of MgATP and L-phenylalaninol, and on the pre-steady-state synthesis and pyrophosphorolysis of the enzyme-phenylalanyladenylate complex in the absence and the presence of tRNA Phe has been measured by established equilibrium and stopped-flow techniques using 2-p-toluidinylnaphthalene-6-sulfonate. At 10 mM Mg2+, the association of enzyme and MgATP is biphasic with dissociation constants of 0.25 +/- 0.03 and 9.1 +/- 1.7 mM. At 2 mM Mg2+, a single dissociation constant of 5.0 +/- 0.5 mM is indicated. The coupling constant of the synergistic reaction is 15 at 1 mM Mg2+ and 290 at 10 mM Mg2+. The Hill constant of the sigmoidal dependence is 3.6. The strengthening of the synergism is believed to reflect a Mg2+-dependent coupling of the synergistic reactions at the two active sites of the enzyme, the coupling being negligible at 1 mM and maximal at 10 mM Mg2+. The pre-steady-state rate of adenylate synthesis is accelerated by the presence of Mg2+. The effect is to decrease the value of the Michaelis-Menten constant of MgATP. Another effect is to increase the rate constant when tRNA Phe is present. At subsaturating [MgATP], the [Mg2+] dependence of the observed rate constant is hyperbolical in the absence and sigmoidal (Hill constant, 3.5) in the presence of tRNA Phe. The rate of the pyrophosphorolysis is enhanced by a decrease of the Michaelis-Menten constant of MgPPi. The effects on the thermodynamics and kinetics parallel the occupancy of the low-affinity Mg2+-binding sites of the enzyme."}
{"id": "PMID:224919", "title": "Characterization of a novel collagen chain in human placenta and its relation to AB collagen.", "content": "A novel collagen chain, termed alpha C, has been isolated from human placenta by limited pepsin digestion. The collagen containing the alpha C chain copurifies with placental AB collagen during selective salt precipitation but is virtually absent from fetal birth membranes, which contain relatively larger amounts of AB. Both native AB and alpha C-containing collagens are resistant to human skin collagenase under conditions that support cleavage of type I by greater than 90%. The alpha C chain was separated from alpha B by phosphocellulose chromatography and subsequently from alpha P by chromatography on CM-cellulose. Its amino acid composition is distinct from alpha A and alha B although all three chains posses compositional features in common; the carbohydrate content of the alpha C chain was intermediate between those of alpha A and alpha B. Analysis by NaDodSO4-polyacrylamide gel electrophoresis of peptides produced by CNBr cleavage and by limited digestion with the enzyme mast cell protease indicated different and unique products for the alpha A, alpha B, and alpha C chains. The data support the existence of another collagen chain which is related to the alpha A and alpha B chains but which is structurally unique. The proteins containing these chains may in turn comprise a subfamily of collagen isotypes which represents a divergence from and/or specialization of the type IV basement membrane collagens.", "contents": "Characterization of a novel collagen chain in human placenta and its relation to AB collagen. A novel collagen chain, termed alpha C, has been isolated from human placenta by limited pepsin digestion. The collagen containing the alpha C chain copurifies with placental AB collagen during selective salt precipitation but is virtually absent from fetal birth membranes, which contain relatively larger amounts of AB. Both native AB and alpha C-containing collagens are resistant to human skin collagenase under conditions that support cleavage of type I by greater than 90%. The alpha C chain was separated from alpha B by phosphocellulose chromatography and subsequently from alpha P by chromatography on CM-cellulose. Its amino acid composition is distinct from alpha A and alha B although all three chains posses compositional features in common; the carbohydrate content of the alpha C chain was intermediate between those of alpha A and alpha B. Analysis by NaDodSO4-polyacrylamide gel electrophoresis of peptides produced by CNBr cleavage and by limited digestion with the enzyme mast cell protease indicated different and unique products for the alpha A, alpha B, and alpha C chains. The data support the existence of another collagen chain which is related to the alpha A and alpha B chains but which is structurally unique. The proteins containing these chains may in turn comprise a subfamily of collagen isotypes which represents a divergence from and/or specialization of the type IV basement membrane collagens."}
{"id": "PMID:224920", "title": "Interaction of a paramagnetic analogue of oxaloacetate with citrate synthase.", "content": "Electron paramagnetic resonance studies have indicated that nitrosodisulfonate binds to pig heart citrate synthase. Titration of the enzyme with nitrosodisulfonate revealed several binding sites for the probe per subunit with one site (KD approximately 0.1 mM) having a greater affinity than the others. The substrate, oxaloacetate, competed very effectively for one of the nitrosodisulfonate binding sites (KD less than 10(-2) mM) at the same time eliminating the weaker probe binding sites. Citrate and (R)- and (S)-malates also displaced the probe. Failure to resolve low- and high-field shoulder in the high gain--high modulation electron paramagnetic resonance spectra of the enzyme--nitrosodisulfonate system indicated that the bound probe was \"weakly immobilized\". However, the electron paramagnetic resonance spectrum of the bound probe changed to one typical of a \"strongly immobilized\" nitroxide upon the addition of a saturating concentration of the substrate acetyl coenzyme A (acetyl-CoA) to the enzyme--nitrosodisulfonate system, indicating the formation of a ternary acetyl-CoA-enzyme-probe complex. Titration of the acetyl-CoA saturated enzyme with the probe indicated one binding site per subunit (KD = 0.37 mM). Thus, nitrosodisulfonate may be considered as a paramagnetic analogue of oxaloacetate in its interaction with citrate synthase. These results are compared with our previous studies with this enzyme, employing a spin-labeled acyl coenzyme A (acyl-CoA) derivative [Weidman, S. W., Drysdale, G. R., & Mildvan, A. S. (1973) Biochemistry 12, 1874--1883].", "contents": "Interaction of a paramagnetic analogue of oxaloacetate with citrate synthase. Electron paramagnetic resonance studies have indicated that nitrosodisulfonate binds to pig heart citrate synthase. Titration of the enzyme with nitrosodisulfonate revealed several binding sites for the probe per subunit with one site (KD approximately 0.1 mM) having a greater affinity than the others. The substrate, oxaloacetate, competed very effectively for one of the nitrosodisulfonate binding sites (KD less than 10(-2) mM) at the same time eliminating the weaker probe binding sites. Citrate and (R)- and (S)-malates also displaced the probe. Failure to resolve low- and high-field shoulder in the high gain--high modulation electron paramagnetic resonance spectra of the enzyme--nitrosodisulfonate system indicated that the bound probe was \"weakly immobilized\". However, the electron paramagnetic resonance spectrum of the bound probe changed to one typical of a \"strongly immobilized\" nitroxide upon the addition of a saturating concentration of the substrate acetyl coenzyme A (acetyl-CoA) to the enzyme--nitrosodisulfonate system, indicating the formation of a ternary acetyl-CoA-enzyme-probe complex. Titration of the acetyl-CoA saturated enzyme with the probe indicated one binding site per subunit (KD = 0.37 mM). Thus, nitrosodisulfonate may be considered as a paramagnetic analogue of oxaloacetate in its interaction with citrate synthase. These results are compared with our previous studies with this enzyme, employing a spin-labeled acyl coenzyme A (acyl-CoA) derivative [Weidman, S. W., Drysdale, G. R., & Mildvan, A. S. (1973) Biochemistry 12, 1874--1883]."}
{"id": "PMID:224923", "title": "Isolation and characterization of cardiac sarcolemma.", "content": "A procedure was developed for the isolation of cardiac sarcolemmal vesicles. These vesicles are enriched about ten-fold (with respect to the tissue homogenate) in K+-stimulated p-nitrophenylphosphatase, (Na+ + K+)-ATPase, 5'-nucleotidase activities and sialic acid content, all of which are believed to be components of the sarcolemma. The sarcolemma of tissue culture cardiac cells were radioiodinated and the distribution of this radioiodine paralleled the distribution of the other membrane markers above. There was very little contamination of the sarcolemmal fraction by sarcoplasmic reticulum (as judged by Ca2+-ATPase and glucose-6-phosphatase activities) or inner mitochondrial membranes (as judged by succinate dehydrogenase activity). There may, however, be some contamination by outer mitochondrial membranes (as judged by monoamine oxidase and rotenone-insensitive NADH cytochrome c reductase activities) which have rarely been monitored in cardiac sarcolemmal preparations. The purity of this preparation is good when compared with other cardiac sarcolemmal preparations. This preparation should be very useful in studying the roles of the cardiac sarcolemma (e.g. in excitation contraction coupling and Ca2+ binding).", "contents": "Isolation and characterization of cardiac sarcolemma. A procedure was developed for the isolation of cardiac sarcolemmal vesicles. These vesicles are enriched about ten-fold (with respect to the tissue homogenate) in K+-stimulated p-nitrophenylphosphatase, (Na+ + K+)-ATPase, 5'-nucleotidase activities and sialic acid content, all of which are believed to be components of the sarcolemma. The sarcolemma of tissue culture cardiac cells were radioiodinated and the distribution of this radioiodine paralleled the distribution of the other membrane markers above. There was very little contamination of the sarcolemmal fraction by sarcoplasmic reticulum (as judged by Ca2+-ATPase and glucose-6-phosphatase activities) or inner mitochondrial membranes (as judged by succinate dehydrogenase activity). There may, however, be some contamination by outer mitochondrial membranes (as judged by monoamine oxidase and rotenone-insensitive NADH cytochrome c reductase activities) which have rarely been monitored in cardiac sarcolemmal preparations. The purity of this preparation is good when compared with other cardiac sarcolemmal preparations. This preparation should be very useful in studying the roles of the cardiac sarcolemma (e.g. in excitation contraction coupling and Ca2+ binding)."}
{"id": "PMID:224924", "title": "Relationship of growth temperature and thermotropic lipid phase changes in cytoplasmic and outer membranes from Escherichia coli K12.", "content": "Purified cytoplasmic and outer membranes isolated from cells of wild type Escherichia coli grown at 12, 20, 37 and 43 degrees C were labelled with the fatty acid spin probe 5-doxyl stearate. Electron spin resonance spectroscopy revealed broad thermotropic phase changes. The inherent viscosity of both membranes was found to increase as a function of elevated growth temperature. The lipid order to disorder transition in the outer membrane but not the cytoplasmic membrane was dramatically affected by the temperature of growth. As a result, the cytoplasmic membrane presumably existed in a gel + liquid crystalline state during cellular growth at 12 and 20 degrees C, but in a liquid crystalline state when cells were grown at 37 and 43 degrees C. In contrast, the outer membrane apparently existed in a gel + liquid crystalline state at all incubation temperatures. Data presented here indicate that the temperature range over which the cell can maintain the outer membrane phospholipids in a mixed (presumedly gel + liquid crystalline) state correlates with the temperature range over which growth occurs.", "contents": "Relationship of growth temperature and thermotropic lipid phase changes in cytoplasmic and outer membranes from Escherichia coli K12. Purified cytoplasmic and outer membranes isolated from cells of wild type Escherichia coli grown at 12, 20, 37 and 43 degrees C were labelled with the fatty acid spin probe 5-doxyl stearate. Electron spin resonance spectroscopy revealed broad thermotropic phase changes. The inherent viscosity of both membranes was found to increase as a function of elevated growth temperature. The lipid order to disorder transition in the outer membrane but not the cytoplasmic membrane was dramatically affected by the temperature of growth. As a result, the cytoplasmic membrane presumably existed in a gel + liquid crystalline state during cellular growth at 12 and 20 degrees C, but in a liquid crystalline state when cells were grown at 37 and 43 degrees C. In contrast, the outer membrane apparently existed in a gel + liquid crystalline state at all incubation temperatures. Data presented here indicate that the temperature range over which the cell can maintain the outer membrane phospholipids in a mixed (presumedly gel + liquid crystalline) state correlates with the temperature range over which growth occurs."}
{"id": "PMID:224925", "title": "Synaptic membrane proteins as substrates for cyclic AMP-stimulated protein phosphorylation in various regions of rat brain.", "content": "Synaptosomal plasma membranes from mammalian brain contain protein kinase activity which phosphorylates endogenous membrane proteins and is stimulated by cyclic AMP. Using polyacrylamide gel electrophoresis it was shown that at least ten proteins in the synaptosomal plasma membrane fraction could be phosphorylated by endogenous cyclic AMP-stimulated protein kinase activity. The number of proteins whose phosphorylation was stimulated by cyclic AMP was strongly influenced by the pH and Mg2+ concentration used in the phosphorylation reaction. A complex pattern of cyclic AMP-stimulated protein phosphorylation was obtained only with synaptosomal plasma membranes and a crude microsomal fraction. Mitochondrial and myelin fractions exhibited no cyclic AMP-stimulated protein kinase activity. Investigation of the distribution of substrates for cyclic AMP-stimulated phosphorylation among various brain regions failed to reveal any regional differences.", "contents": "Synaptic membrane proteins as substrates for cyclic AMP-stimulated protein phosphorylation in various regions of rat brain. Synaptosomal plasma membranes from mammalian brain contain protein kinase activity which phosphorylates endogenous membrane proteins and is stimulated by cyclic AMP. Using polyacrylamide gel electrophoresis it was shown that at least ten proteins in the synaptosomal plasma membrane fraction could be phosphorylated by endogenous cyclic AMP-stimulated protein kinase activity. The number of proteins whose phosphorylation was stimulated by cyclic AMP was strongly influenced by the pH and Mg2+ concentration used in the phosphorylation reaction. A complex pattern of cyclic AMP-stimulated protein phosphorylation was obtained only with synaptosomal plasma membranes and a crude microsomal fraction. Mitochondrial and myelin fractions exhibited no cyclic AMP-stimulated protein kinase activity. Investigation of the distribution of substrates for cyclic AMP-stimulated phosphorylation among various brain regions failed to reveal any regional differences."}
{"id": "PMID:224926", "title": "Direct photoaffinity labeling of the primary region of the ouabain binding site of (Na+ + K+)-ATPase with [3H]ouabain, [3H]digitoxin and [3H]digitoxigenin.", "content": "The tritiated cardiotonic steroids, ouabain, digitoxin, and digitoxigenin are shown to photolabel the large polypeptide but not the glycoprotein or proteolipid component of the (Na+ + K+)-ATPase when they are bound to the inhibitory site and exposed to light of 220 or 254 nm. The extent of photolabeling is low, less than 1%, and is limited by photocross-linking of the enzyme. The mechanism of photoincorporation does not appear to be either photolysis of the lactone ring in ouabain or photolysis of tryptophan or tyrosine residues in the polypeptide.", "contents": "Direct photoaffinity labeling of the primary region of the ouabain binding site of (Na+ + K+)-ATPase with [3H]ouabain, [3H]digitoxin and [3H]digitoxigenin. The tritiated cardiotonic steroids, ouabain, digitoxin, and digitoxigenin are shown to photolabel the large polypeptide but not the glycoprotein or proteolipid component of the (Na+ + K+)-ATPase when they are bound to the inhibitory site and exposed to light of 220 or 254 nm. The extent of photolabeling is low, less than 1%, and is limited by photocross-linking of the enzyme. The mechanism of photoincorporation does not appear to be either photolysis of the lactone ring in ouabain or photolysis of tryptophan or tyrosine residues in the polypeptide."}
{"id": "PMID:224927", "title": "The interaction of 3,3',4',5-tetrachlorosalicylanilide with phosphatidylcholine bilayers.", "content": "1. The interaction of the germicide 3,3',4',5-tetrachlorosalicylanilide (T4CS) with vesicles and dispersions of egg phosphatidylcholine has been studied by gel permeation chromatography, electron microscopy, electron spin resonance spin labelling and ion permeability measurements. 2. Incorporation of T4CS into vesicles of egg phosphatidylcholine gives rise to a large increase in the permeability rate of the paramagnetic cation N,N-dimethyl-N-(1'-oxyl-2',2',6',6'-tetramethyl-4'-piperidyl)-2-hydroxyethylammonium chloride through the lipid bilayer but has no significant effect on the vesicle sizes as measured by gel permeation chromatography or electron microscopy. 3. ESR studies using a spin-labelled fatty acid have demonstrated the presence of two different environments for the spin label when T4CS is incorporated into phosphatidylcholine bilayers. These two environments are identified as (a) highly ordered areas of the bilayer, rich in T4CS and (b) areas with very similar ordering to that in pure egg phosphatidylcholine. 4. The effectiveness of very low concentrations of the germicide in increasing vesicle permeability is explained in terms of its clustering to give rigid patches, rich in T4CS, rather than being evenly distributed throughout the bilayer. It is proposed that the increased ion permeability arises from leakage at the interfaces between the rigid and flexible regions of the lipid bilayer. 5. Comparisons between the effective levels of T4CS in phosphatidylcholine vesicles and its minimum inhibitory concentration with a Gram-positive bacterium confirm the validity of phospholipid vesicles as a model for studies of germicidal activity.", "contents": "The interaction of 3,3',4',5-tetrachlorosalicylanilide with phosphatidylcholine bilayers. 1. The interaction of the germicide 3,3',4',5-tetrachlorosalicylanilide (T4CS) with vesicles and dispersions of egg phosphatidylcholine has been studied by gel permeation chromatography, electron microscopy, electron spin resonance spin labelling and ion permeability measurements. 2. Incorporation of T4CS into vesicles of egg phosphatidylcholine gives rise to a large increase in the permeability rate of the paramagnetic cation N,N-dimethyl-N-(1'-oxyl-2',2',6',6'-tetramethyl-4'-piperidyl)-2-hydroxyethylammonium chloride through the lipid bilayer but has no significant effect on the vesicle sizes as measured by gel permeation chromatography or electron microscopy. 3. ESR studies using a spin-labelled fatty acid have demonstrated the presence of two different environments for the spin label when T4CS is incorporated into phosphatidylcholine bilayers. These two environments are identified as (a) highly ordered areas of the bilayer, rich in T4CS and (b) areas with very similar ordering to that in pure egg phosphatidylcholine. 4. The effectiveness of very low concentrations of the germicide in increasing vesicle permeability is explained in terms of its clustering to give rigid patches, rich in T4CS, rather than being evenly distributed throughout the bilayer. It is proposed that the increased ion permeability arises from leakage at the interfaces between the rigid and flexible regions of the lipid bilayer. 5. Comparisons between the effective levels of T4CS in phosphatidylcholine vesicles and its minimum inhibitory concentration with a Gram-positive bacterium confirm the validity of phospholipid vesicles as a model for studies of germicidal activity."}
{"id": "PMID:224928", "title": "Smooth muscle cell sarcolemma. Purification and properties of plasma membranes from the rat uterus.", "content": "A membrane fraction with sarcolemmal properties was purified from the smooth muscle layers (myometrium) of rat uterus by successive differential and equilibrium centrifugation in sucrose. The putative sarcolemmal fraction was identified by iodination with [125I]iodosulfanilic acid, had an equilibrium density of 1.15, and was enriched in enzyme activities usually associated with the plasma membrane including 5'-nucleotidase (EC 3.1.3.5) and (Na+ + K+) ATPase (EC 3.6.1.3). These membranes were free of mitochondrial or nuclear membrane contamination, suggesting the relative enrichment of sarcolemmal membranes in the fraction. Proteins of the membranes were heterogeneous with respect to molecular weight, but only a few were labelled when intact muscle was radioiodinated. Uniform resistance of sarcolemmal proteins to trypsin digestion and salt extraction suggested many are tightly bound or intrinsic membrane proteins and was a further indication of the homogeneity of membranes in this fraction.", "contents": "Smooth muscle cell sarcolemma. Purification and properties of plasma membranes from the rat uterus. A membrane fraction with sarcolemmal properties was purified from the smooth muscle layers (myometrium) of rat uterus by successive differential and equilibrium centrifugation in sucrose. The putative sarcolemmal fraction was identified by iodination with [125I]iodosulfanilic acid, had an equilibrium density of 1.15, and was enriched in enzyme activities usually associated with the plasma membrane including 5'-nucleotidase (EC 3.1.3.5) and (Na+ + K+) ATPase (EC 3.6.1.3). These membranes were free of mitochondrial or nuclear membrane contamination, suggesting the relative enrichment of sarcolemmal membranes in the fraction. Proteins of the membranes were heterogeneous with respect to molecular weight, but only a few were labelled when intact muscle was radioiodinated. Uniform resistance of sarcolemmal proteins to trypsin digestion and salt extraction suggested many are tightly bound or intrinsic membrane proteins and was a further indication of the homogeneity of membranes in this fraction."}
{"id": "PMID:224929", "title": "Isolation of neuronal plasma membranes from the crayfish Procamburus clarkii, with an aqueous two phase polymer system followed by sucrose density gradient centrifugation.", "content": "An aqueous two phase polymer system (Dextran-polyethyleneglycol system was developed for isolation of plasma membrane fraction from nerves of the crayfish, Procamburus clarkii. The polymer system effectively reduced both mitochondrial and endoplasmic reticulum marker enzyme activity from a crude membrane fraction. The similar enrichment of (Na+ + K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) was shown by the polymer system as well as by the sucrose density gradient centrifugation. The purified plasma membrane fraction (PM) was obtained using the polymer system followed by sucrose density gradient centrifugation. The PM fraction had a high specific activity of (Na + K+)-ATPase of up to 17 times that in the homogenate, with smaller contamination by mitochondria and endoplasmic reticulum enzyme activities than any other membrane fraction. Electron micrographs of the PM fraction also supported the above evidences. The protein recovered from the PM fraction amounted to 1.1% of the total protein in the homogenate. The specific activity of acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) in the membrane fractions was less increased than that of (Na+ + K+)-ATPase. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis suggested that polypeptide chains of estimated molecular weight 115,000 and 31,000 were enriched in the plasma membranes of the crayfish nerves.", "contents": "Isolation of neuronal plasma membranes from the crayfish Procamburus clarkii, with an aqueous two phase polymer system followed by sucrose density gradient centrifugation. An aqueous two phase polymer system (Dextran-polyethyleneglycol system was developed for isolation of plasma membrane fraction from nerves of the crayfish, Procamburus clarkii. The polymer system effectively reduced both mitochondrial and endoplasmic reticulum marker enzyme activity from a crude membrane fraction. The similar enrichment of (Na+ + K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) was shown by the polymer system as well as by the sucrose density gradient centrifugation. The purified plasma membrane fraction (PM) was obtained using the polymer system followed by sucrose density gradient centrifugation. The PM fraction had a high specific activity of (Na + K+)-ATPase of up to 17 times that in the homogenate, with smaller contamination by mitochondria and endoplasmic reticulum enzyme activities than any other membrane fraction. Electron micrographs of the PM fraction also supported the above evidences. The protein recovered from the PM fraction amounted to 1.1% of the total protein in the homogenate. The specific activity of acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) in the membrane fractions was less increased than that of (Na+ + K+)-ATPase. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis suggested that polypeptide chains of estimated molecular weight 115,000 and 31,000 were enriched in the plasma membranes of the crayfish nerves."}
{"id": "PMID:224930", "title": "Purification and partial characterization of aldehyde dehydrogenase from human erythrocytes.", "content": "Human erythrocyte aldehyde dehydrogenase (aldehyde:NAD+ oxidoreductase, EC 1.2.1.3) was purified to apparent homogeneity. The native enzyme has a molecular weight of about 210,000 as determined by gel filtration, and SDS-polyacrylamide gel electrophoresis of this enzyme yields a single protein and with a molecular weight of 51,500, suggesting that the native enzyme may be a tetramer. The enzyme has a relatively low Km for NAD (15 microM) and a high sensitivity to disulfiram. Disulfiram inhibits the enzyme activity rapidly and this inhibition is apparently of a non-competitive nature. In kinetic characteristic and sensitivity to disulfiram, erythrocyte aldehyde dehydrogenase closely resembles the cytosolic aldehyde dehydrogenase found in the liver of various species of mammalians.", "contents": "Purification and partial characterization of aldehyde dehydrogenase from human erythrocytes. Human erythrocyte aldehyde dehydrogenase (aldehyde:NAD+ oxidoreductase, EC 1.2.1.3) was purified to apparent homogeneity. The native enzyme has a molecular weight of about 210,000 as determined by gel filtration, and SDS-polyacrylamide gel electrophoresis of this enzyme yields a single protein and with a molecular weight of 51,500, suggesting that the native enzyme may be a tetramer. The enzyme has a relatively low Km for NAD (15 microM) and a high sensitivity to disulfiram. Disulfiram inhibits the enzyme activity rapidly and this inhibition is apparently of a non-competitive nature. In kinetic characteristic and sensitivity to disulfiram, erythrocyte aldehyde dehydrogenase closely resembles the cytosolic aldehyde dehydrogenase found in the liver of various species of mammalians."}
{"id": "PMID:224931", "title": "Subunit interactions in rabbit-muscle glyceraldehyde-phosphate dehydrogenase, as measured by NAD+ and NADH binding.", "content": "1. The binding parameters for NADH and NAD+ to rabbit-muscle glyceraldehyde-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate:NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12) have been measured by quenching of the flourescence of the protein and the NADH. 2. The fact that the degree of protein fluorescence quenching by bound NAD+ or NADH, excited at 285 nm and measured at 340 nm ('blue' tryptophans), is not linearly related to the saturation functions of these nucleotides, leads to a slight overestimation of the interaction energy and an underestimation of the concentration of sites, if linearity is assumed. 3. This is also the case for NADH, but not for NAD+, when the protein fluorescence is excited at 305 nm and measured at 390 nm ('red' tryptophans). 4. The binding of NAD+ can be described by a model in which the binding of NAD+, via negative interactions within the dimer, induces weaker binding sites, with the result that the microscopic dissociation constant is 0.08 microM at low saturation and 0.18 microM for the holoenzyme. 5. The binding of NADH can be described on the basis of the same model, the dissociation constant at low saturation being 0.5 microM and of the holoenzyme 1.0 microM. 6. The fluorescence of bound NADH is not sensitive to the conformational changes that cause the decrease in affinity of bound NAD+ or NADH. 7. The binding of NAD+ to the 3-phosphoglyceroyl enzyme can be described by a dissociation constant that is at least two orders of magnitude greater than the dissociation constants of the unacylated enzyme. The affinity of NAD+ to this form of the enzyme is in agreement with the Ki calculated from product inhibition by NAD+ of the reductive dephosphorylation of 1,3-diphosphoglycerate.", "contents": "Subunit interactions in rabbit-muscle glyceraldehyde-phosphate dehydrogenase, as measured by NAD+ and NADH binding. 1. The binding parameters for NADH and NAD+ to rabbit-muscle glyceraldehyde-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate:NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12) have been measured by quenching of the flourescence of the protein and the NADH. 2. The fact that the degree of protein fluorescence quenching by bound NAD+ or NADH, excited at 285 nm and measured at 340 nm ('blue' tryptophans), is not linearly related to the saturation functions of these nucleotides, leads to a slight overestimation of the interaction energy and an underestimation of the concentration of sites, if linearity is assumed. 3. This is also the case for NADH, but not for NAD+, when the protein fluorescence is excited at 305 nm and measured at 390 nm ('red' tryptophans). 4. The binding of NAD+ can be described by a model in which the binding of NAD+, via negative interactions within the dimer, induces weaker binding sites, with the result that the microscopic dissociation constant is 0.08 microM at low saturation and 0.18 microM for the holoenzyme. 5. The binding of NADH can be described on the basis of the same model, the dissociation constant at low saturation being 0.5 microM and of the holoenzyme 1.0 microM. 6. The fluorescence of bound NADH is not sensitive to the conformational changes that cause the decrease in affinity of bound NAD+ or NADH. 7. The binding of NAD+ to the 3-phosphoglyceroyl enzyme can be described by a dissociation constant that is at least two orders of magnitude greater than the dissociation constants of the unacylated enzyme. The affinity of NAD+ to this form of the enzyme is in agreement with the Ki calculated from product inhibition by NAD+ of the reductive dephosphorylation of 1,3-diphosphoglycerate."}
{"id": "PMID:224932", "title": "Determination of binding parameters of cyclic AMP and its analogs to cyclic AMP-dependent protein kinase by the fluorescent probe method.", "content": "The method for determination of dissociation constants for cyclic AMP and its analogs bound to cyclic AMP-dependent protein kinase from pig brain is described. The technique for measuring the binding parameters of the ligands is based on the changes in the fluorescent spectrum of etheno cyclic AMP once it is bound to protein kinase. The dissociation constants for a number of nonfluorescent cyclic AMP analogs were determined in the competitive displacement of etheno cyclic AMP by these analogs. The number of cyclic AMP-binding sites in the pig brain protein kinase was found to be 2.2; no cooperativity was observed upon binding. The holoenzyme complex (Mr = 180,000) of the protein kinase under study was established to have the stoichiometry of R2C2 type under native conditions.", "contents": "Determination of binding parameters of cyclic AMP and its analogs to cyclic AMP-dependent protein kinase by the fluorescent probe method. The method for determination of dissociation constants for cyclic AMP and its analogs bound to cyclic AMP-dependent protein kinase from pig brain is described. The technique for measuring the binding parameters of the ligands is based on the changes in the fluorescent spectrum of etheno cyclic AMP once it is bound to protein kinase. The dissociation constants for a number of nonfluorescent cyclic AMP analogs were determined in the competitive displacement of etheno cyclic AMP by these analogs. The number of cyclic AMP-binding sites in the pig brain protein kinase was found to be 2.2; no cooperativity was observed upon binding. The holoenzyme complex (Mr = 180,000) of the protein kinase under study was established to have the stoichiometry of R2C2 type under native conditions."}
{"id": "PMID:224934", "title": "The role of ferrichrome reductase in iron metabolism of Ustilago sphaerogena.", "content": "Ferrichrome, the ferric ionophore for Ustilago sphaerogena, can serve as a source of iron for the enzyme ferrochelatase (protoheme ferrolyase, EC 4.99.1.1) in this organism, but only after enzymatic removal of the iron from its carrier. U. sphaerogena contains a specific ferrichrome reductase (NADH:ferrichrome oxidoreductase) which catalyzes cellular dissociation of the complex by reduction of the metal to the ferrous state. A spectrophotometric assay was developed based on trapping of the ferrous ion produced by ferrozine. There is an apparent inhibition by oxygen which is thought to be due to re-oxidation of the metal under the assay conditions. The close structural analogue, ferrichrome A, is not a substrate, nor is the ester type siderochrome ferric hexahydro-N,N',N\"-triacetylfusarinine C. Aluminum desferriferrichrome is inhibitory. The importance of this enzyme for the metabolism of iron in this organism is discussed.", "contents": "The role of ferrichrome reductase in iron metabolism of Ustilago sphaerogena. Ferrichrome, the ferric ionophore for Ustilago sphaerogena, can serve as a source of iron for the enzyme ferrochelatase (protoheme ferrolyase, EC 4.99.1.1) in this organism, but only after enzymatic removal of the iron from its carrier. U. sphaerogena contains a specific ferrichrome reductase (NADH:ferrichrome oxidoreductase) which catalyzes cellular dissociation of the complex by reduction of the metal to the ferrous state. A spectrophotometric assay was developed based on trapping of the ferrous ion produced by ferrozine. There is an apparent inhibition by oxygen which is thought to be due to re-oxidation of the metal under the assay conditions. The close structural analogue, ferrichrome A, is not a substrate, nor is the ester type siderochrome ferric hexahydro-N,N',N\"-triacetylfusarinine C. Aluminum desferriferrichrome is inhibitory. The importance of this enzyme for the metabolism of iron in this organism is discussed."}
{"id": "PMID:224935", "title": "Improved in vitro light activation and assay systems for two spinach chloroplast enzymes.", "content": "An improved system for the in vitro light activation of the chloroplast enzymes fructose-1,6-bisphosphatase and NADP-dependent malate dehydrogenase is described. Through the presence of the monothiol beta-mercaptoethanol in the reaction mixtures the activated forms of the enzymes can be stabilized and their activity determined spectrophotometrically.", "contents": "Improved in vitro light activation and assay systems for two spinach chloroplast enzymes. An improved system for the in vitro light activation of the chloroplast enzymes fructose-1,6-bisphosphatase and NADP-dependent malate dehydrogenase is described. Through the presence of the monothiol beta-mercaptoethanol in the reaction mixtures the activated forms of the enzymes can be stabilized and their activity determined spectrophotometrically."}
{"id": "PMID:224936", "title": "Characterization of undecaprenol kinase from Lactobacillus plantarum.", "content": "A membrane-bound undecaprenol kinase from Lactobacillus has been identified by observing the ATP-dependent phosphorylation of [14C]undercaprenol. The product of this reaction was shown to be [14C]undecaprenyl monophosphate by comparison of its chromatographic mobilities with authentic undecaprenyl monophosphate. It was shown that 32P from [gamma-32P]ATP was incorporated into undecaprenyl monophosphate. The kinase was partially solubilized by a variety of methods utilizing Triton X-100. Both the membrane-associated and solubilized enzymes required Mg2+, Triton X-100 and dimethylsulfoxide for activity. The enzyme preferentially phosphorylated the C34, C50 AND C 55 polyprenols. Geranylgeraniol (C20) and dolichol (C100), however, were utilized only 6% and 13% as well as undecaprenol, respectively. Despite the 8-fold difference in apparent V values, the apparent Km values for dolichol and undecaprenol were both 14 microM. The apparent Km for the nucleotide cosubstrate, ATP, was 2 mM. No other nucleoside triphosphate could substitute for ATP.", "contents": "Characterization of undecaprenol kinase from Lactobacillus plantarum. A membrane-bound undecaprenol kinase from Lactobacillus has been identified by observing the ATP-dependent phosphorylation of [14C]undercaprenol. The product of this reaction was shown to be [14C]undecaprenyl monophosphate by comparison of its chromatographic mobilities with authentic undecaprenyl monophosphate. It was shown that 32P from [gamma-32P]ATP was incorporated into undecaprenyl monophosphate. The kinase was partially solubilized by a variety of methods utilizing Triton X-100. Both the membrane-associated and solubilized enzymes required Mg2+, Triton X-100 and dimethylsulfoxide for activity. The enzyme preferentially phosphorylated the C34, C50 AND C 55 polyprenols. Geranylgeraniol (C20) and dolichol (C100), however, were utilized only 6% and 13% as well as undecaprenol, respectively. Despite the 8-fold difference in apparent V values, the apparent Km values for dolichol and undecaprenol were both 14 microM. The apparent Km for the nucleotide cosubstrate, ATP, was 2 mM. No other nucleoside triphosphate could substitute for ATP."}
{"id": "PMID:224937", "title": "Purification and characterization of a 15-ketoprostaglandin delta 13-reductase from bovine lung.", "content": "15-Ketoprostaglandin delta 13-reductase from bovine lung has been purified using affinity chromatography to apparent homogeneity, as judged from polyacrylamide gel electrophoresis with and without sodium dodecyl sulphate. Valine was identified as tne N-terminal aumino acid, and the isoelectric point was estimated at pH 7.8. Molecular weights of 56,000 and 39,500 were found by the use of gel filtration and SDS-polyacrylamide gel electrophoresis, respectively. The enzyme was found to be specific for the 15-keto group, thus 15-ketoprostaglandin E4 (apparent Km = microM) is a substrate, in contrast to prostaglandin E1. The enzyme was active with both NADH (apparent Km = 88--94 microM) and NADH (apparent Km = 5--9 microM) as coenzyme, but the V max with NADH was more than twice that obtained with NADPH. The enzyme did not catalyze the reversed reaction: 13,14-dihydro-15-keto-prostaglandin E1 to 15-ketoprostaglandin E1. The turnover number of the enzyme was determined to be either 60 or 42 min-1. The low value of the turnover number is compensated by a high concentration (96.4 mU/g tissue) of the enzyme in lung tissue, resulting in a high metabolic capacity. Thus, 15-ketoprostaglandin delta 13-reductase together with 15-hydroxyprostaglandin dehydrogenase ensures an irreversible catabolism of prostaglandins.", "contents": "Purification and characterization of a 15-ketoprostaglandin delta 13-reductase from bovine lung. 15-Ketoprostaglandin delta 13-reductase from bovine lung has been purified using affinity chromatography to apparent homogeneity, as judged from polyacrylamide gel electrophoresis with and without sodium dodecyl sulphate. Valine was identified as tne N-terminal aumino acid, and the isoelectric point was estimated at pH 7.8. Molecular weights of 56,000 and 39,500 were found by the use of gel filtration and SDS-polyacrylamide gel electrophoresis, respectively. The enzyme was found to be specific for the 15-keto group, thus 15-ketoprostaglandin E4 (apparent Km = microM) is a substrate, in contrast to prostaglandin E1. The enzyme was active with both NADH (apparent Km = 88--94 microM) and NADH (apparent Km = 5--9 microM) as coenzyme, but the V max with NADH was more than twice that obtained with NADPH. The enzyme did not catalyze the reversed reaction: 13,14-dihydro-15-keto-prostaglandin E1 to 15-ketoprostaglandin E1. The turnover number of the enzyme was determined to be either 60 or 42 min-1. The low value of the turnover number is compensated by a high concentration (96.4 mU/g tissue) of the enzyme in lung tissue, resulting in a high metabolic capacity. Thus, 15-ketoprostaglandin delta 13-reductase together with 15-hydroxyprostaglandin dehydrogenase ensures an irreversible catabolism of prostaglandins."}
{"id": "PMID:224938", "title": "Regulation of lipogenesis in adipocytes. Independent effects of thyroid hormones, cyclic AMP and insulin on the uptake of deoxy-D-glucose.", "content": "Thyroidectomy is known to enhance fat cell phosphodiesterase activity; as a result, the response to lipolytic hormones is markedly reduced. Thyroidectomy also stimulates overall lipogenesis and the uptake of glucose: the present experiments investigated whether there was a correlation between cyclic AMP and glucose uptake. The parameter measured was the transport and phosphorylation (uptake) of deoxy-D-glucose in the presence of two modifiers of the cyclic AMP pool: phosphodiesterase inhibitors and the analogue, dibutyryl cyclic AMP. The inhibition by methylxanthines and dibutyryl cyclic AMP of deoxy-D-glucose uptake observed, was the same in fat cells from normal and thyroidectomized rats: the latter nonetheless still maintained their enhanced glucose uptake. It was therefore concluded that thyroid hormones and cyclic AMP control this step by different, separate pathways. Insulin, well known for its lipogenic effect, enhanced deoxy-D-glucose uptake in fat cells from both normal and thyroidectomized rats to the same extent (about 40%). An additive effect of thyroidectomy and insulin on glucose uptake was thus demonstrated. These results imply that glucose uptake in the adipocyte is controlled by at least three factors: thyroid hormones, cyclic AMP and insulin, each of which can act independently. Maximum glucose uptake is achieved in the presence of a combination of low concentrations of cyclic AMP, of insulin, and in the absence of thyroid hormones.", "contents": "Regulation of lipogenesis in adipocytes. Independent effects of thyroid hormones, cyclic AMP and insulin on the uptake of deoxy-D-glucose. Thyroidectomy is known to enhance fat cell phosphodiesterase activity; as a result, the response to lipolytic hormones is markedly reduced. Thyroidectomy also stimulates overall lipogenesis and the uptake of glucose: the present experiments investigated whether there was a correlation between cyclic AMP and glucose uptake. The parameter measured was the transport and phosphorylation (uptake) of deoxy-D-glucose in the presence of two modifiers of the cyclic AMP pool: phosphodiesterase inhibitors and the analogue, dibutyryl cyclic AMP. The inhibition by methylxanthines and dibutyryl cyclic AMP of deoxy-D-glucose uptake observed, was the same in fat cells from normal and thyroidectomized rats: the latter nonetheless still maintained their enhanced glucose uptake. It was therefore concluded that thyroid hormones and cyclic AMP control this step by different, separate pathways. Insulin, well known for its lipogenic effect, enhanced deoxy-D-glucose uptake in fat cells from both normal and thyroidectomized rats to the same extent (about 40%). An additive effect of thyroidectomy and insulin on glucose uptake was thus demonstrated. These results imply that glucose uptake in the adipocyte is controlled by at least three factors: thyroid hormones, cyclic AMP and insulin, each of which can act independently. Maximum glucose uptake is achieved in the presence of a combination of low concentrations of cyclic AMP, of insulin, and in the absence of thyroid hormones."}
{"id": "PMID:224939", "title": "Differential effects of GTP on the coupling of beta-adrenergic receptors to adenylate cyclase from frog and turkey erythrocytes. Application of new methods for the analysis of receptor-effector coupling.", "content": "A detailed comparison of the interaction of beta-adrenergic receptors with adenylate cyclase stimulation and modification of this interaction by guanine nucleotides has been made in two model systems, the frog and turkey erythrocyte. Objective analysis of the data was facilitated by the development of new graphical methods which involve the use of logit-logit transformations of percent receptor occupancy versus percent enzyme stimulation plots (coupling curves). Receptor-cyclase coupling in turkey erythrocyte membranes demonstrates a proportional relationship between receptor occupancy and adenylate cyclase activation and is unaffected by exogenous guanine nucleotides. By comparison, the proportional relationship of receptor occupancy and adenylate cyclase activation observed in frog erythrocyte membranes in the absence of guanine nucleotides is modified by the addition of exogenous guanine nucleotides such that a greater fractional enzyme stimulation is elicited by low receptor occupancy. Methodological criteria crucial for valid comparison of receptor occupancy and adenylate cyclase activity are delineated. In addition, the possible molecular mechanisms of receptor-cyclase coupling which might give rise to the coupling curves observed are discussed.", "contents": "Differential effects of GTP on the coupling of beta-adrenergic receptors to adenylate cyclase from frog and turkey erythrocytes. Application of new methods for the analysis of receptor-effector coupling. A detailed comparison of the interaction of beta-adrenergic receptors with adenylate cyclase stimulation and modification of this interaction by guanine nucleotides has been made in two model systems, the frog and turkey erythrocyte. Objective analysis of the data was facilitated by the development of new graphical methods which involve the use of logit-logit transformations of percent receptor occupancy versus percent enzyme stimulation plots (coupling curves). Receptor-cyclase coupling in turkey erythrocyte membranes demonstrates a proportional relationship between receptor occupancy and adenylate cyclase activation and is unaffected by exogenous guanine nucleotides. By comparison, the proportional relationship of receptor occupancy and adenylate cyclase activation observed in frog erythrocyte membranes in the absence of guanine nucleotides is modified by the addition of exogenous guanine nucleotides such that a greater fractional enzyme stimulation is elicited by low receptor occupancy. Methodological criteria crucial for valid comparison of receptor occupancy and adenylate cyclase activity are delineated. In addition, the possible molecular mechanisms of receptor-cyclase coupling which might give rise to the coupling curves observed are discussed."}
{"id": "PMID:224943", "title": "Responses of nuclear glucose-6-phosphatase to diabetes and to hydrocortisone administered to normal and diabetic rats differ from those of the microsomal enzyme.", "content": "The effect of alloxan-diabetes, and of pharmacological doses of hydrocortisone administered to normal and diabetic rats, on carbamyl phosphate:glucose phosphotransferase and D-glucose-6-phosphate phosphohydrolase (EC 3.1.3.9) activities of isolated hepatic nuclei and microsomes were studied by assay at pH 7 in the absence and presence of deoxycholate. Hormonally related alterations both in activity levels and in the activation by the detergent (i.e. latency) of activities of the two cellular structural elements differed significantly. Most strikingly, (a) a 3--4-fold increase in the levels of activities of nuclei was seen in response either to diabetes or to hydrocortisone administered to normal rats whether or not detergent was added to preparations prior to assay; (b) the normally low degree of stimulation by detergent of activities of nuclei was unaltered in diabetes, and (c) administration of the glucocorticoid to diabetic rats decreased activity levels and increased their activation by detergent. Directly contrasting responses were noted with isolated microsomal preparations. Fundamental differences in the enzymes in these two organelle preparations are thus demonstrated. It appears that both synthetic and hydrolytic activities of this enzyme of nuclei may be manifest in the presence of requisite substrates, and that activities of this organelle may become increasingly prominent under certain hormonally perturbed conditions.", "contents": "Responses of nuclear glucose-6-phosphatase to diabetes and to hydrocortisone administered to normal and diabetic rats differ from those of the microsomal enzyme. The effect of alloxan-diabetes, and of pharmacological doses of hydrocortisone administered to normal and diabetic rats, on carbamyl phosphate:glucose phosphotransferase and D-glucose-6-phosphate phosphohydrolase (EC 3.1.3.9) activities of isolated hepatic nuclei and microsomes were studied by assay at pH 7 in the absence and presence of deoxycholate. Hormonally related alterations both in activity levels and in the activation by the detergent (i.e. latency) of activities of the two cellular structural elements differed significantly. Most strikingly, (a) a 3--4-fold increase in the levels of activities of nuclei was seen in response either to diabetes or to hydrocortisone administered to normal rats whether or not detergent was added to preparations prior to assay; (b) the normally low degree of stimulation by detergent of activities of nuclei was unaltered in diabetes, and (c) administration of the glucocorticoid to diabetic rats decreased activity levels and increased their activation by detergent. Directly contrasting responses were noted with isolated microsomal preparations. Fundamental differences in the enzymes in these two organelle preparations are thus demonstrated. It appears that both synthetic and hydrolytic activities of this enzyme of nuclei may be manifest in the presence of requisite substrates, and that activities of this organelle may become increasingly prominent under certain hormonally perturbed conditions."}
{"id": "PMID:224944", "title": "Role of cyclic AMP and related enzymes in rat lung growth and development.", "content": "Cyclic AMP levels in rat lungs showed phasic elevations which peaked during fetal, neonatal and late postnatal periods of development. Lung phospholipids showed major alterations in their levels during fetal and early neonatal life. Alterations in glycogen levels were accompanied by parallel changes in phosphorylase a/total phosphorylase activity which may be related to changes in cyclic AMP during development. Cyclic AMP levels were dependent on the relative activities of adenylate cyclase and cyclic AMP phosphodiesterase which also changed with age. Activation of adenylate cyclase by norepinephrine and NaF, and of cyclic AMP phosphodiesterase by calcium, was maximum neonatally and declined variably thereafter. These data suggest a relationship between cyclic AMP, glycogen and phospholipids during rat lung development.", "contents": "Role of cyclic AMP and related enzymes in rat lung growth and development. Cyclic AMP levels in rat lungs showed phasic elevations which peaked during fetal, neonatal and late postnatal periods of development. Lung phospholipids showed major alterations in their levels during fetal and early neonatal life. Alterations in glycogen levels were accompanied by parallel changes in phosphorylase a/total phosphorylase activity which may be related to changes in cyclic AMP during development. Cyclic AMP levels were dependent on the relative activities of adenylate cyclase and cyclic AMP phosphodiesterase which also changed with age. Activation of adenylate cyclase by norepinephrine and NaF, and of cyclic AMP phosphodiesterase by calcium, was maximum neonatally and declined variably thereafter. These data suggest a relationship between cyclic AMP, glycogen and phospholipids during rat lung development."}
{"id": "PMID:224946", "title": "Cell density-dependent increase in prolyl hydroxylase activity in cultured L-929 cells requires de novo protein synthesis.", "content": "Prolyl hydroxylase activity in cultured L-929 cells was found to increase when cells grew from log phase to stationary phase and when cells were harvested at the mid-log phase and replated at higher cell densities. Cycloheximide and actinomycin D inhibited the cell density-dependent increase in prolyl hydroxylase activity indicating that the increase in prolyl hydroxylase activity required de novo synthesis of protein and RNA. Prolyl hydroxylase was purified from cultured L-929 cells and antibodies against the protein were raised in rabbits. The antibodies were used to demonstrate that L-929 cells contained two forms of prolyl hydroxylase: an enzymatically active, tetrameric form consisting of two alpha and two beta polypeptide chains and an enzymatically inactive form containing immunologically cross-reacting protein. The polypeptide chains alpha, beta and cross-reacting protein were obtained by immunoadsorption. Peptide map analysis indicated that cross-reacting protein was similar if not identical to beta in primary structure, and alpha was different from both beta and cross-reacting protein. The results suggested that the prolyl hydroxylase levels in cells or tissues may be regulated by new protein and/or RNA synthesis.", "contents": "Cell density-dependent increase in prolyl hydroxylase activity in cultured L-929 cells requires de novo protein synthesis. Prolyl hydroxylase activity in cultured L-929 cells was found to increase when cells grew from log phase to stationary phase and when cells were harvested at the mid-log phase and replated at higher cell densities. Cycloheximide and actinomycin D inhibited the cell density-dependent increase in prolyl hydroxylase activity indicating that the increase in prolyl hydroxylase activity required de novo synthesis of protein and RNA. Prolyl hydroxylase was purified from cultured L-929 cells and antibodies against the protein were raised in rabbits. The antibodies were used to demonstrate that L-929 cells contained two forms of prolyl hydroxylase: an enzymatically active, tetrameric form consisting of two alpha and two beta polypeptide chains and an enzymatically inactive form containing immunologically cross-reacting protein. The polypeptide chains alpha, beta and cross-reacting protein were obtained by immunoadsorption. Peptide map analysis indicated that cross-reacting protein was similar if not identical to beta in primary structure, and alpha was different from both beta and cross-reacting protein. The results suggested that the prolyl hydroxylase levels in cells or tissues may be regulated by new protein and/or RNA synthesis."}
{"id": "PMID:224947", "title": "Inhibition of the degradation of receptor-bound human choriogonadotropin by leupeptin.", "content": "The ability of leupeptin to block the degradation of receptor-bound human choriogonadotropin has been studied. It was found that this compound inhibited hormone degradation and intracellular cathepsin B activity in a parallel fasion, without affecting hormone-stimulated steroidogenesis.", "contents": "Inhibition of the degradation of receptor-bound human choriogonadotropin by leupeptin. The ability of leupeptin to block the degradation of receptor-bound human choriogonadotropin has been studied. It was found that this compound inhibited hormone degradation and intracellular cathepsin B activity in a parallel fasion, without affecting hormone-stimulated steroidogenesis."}
{"id": "PMID:224949", "title": "[ESR of adsorbed chlorophyll a].", "content": "Oxygen and water vapour effect on the dark ESR signal of chlorophyll a adsorbed on silica in vacuum has been studied. It has been determined that when O2 and H2O are absent chlorophyll a adsorption is accompanied by an increase of the paramagnetic states portion (PSP) of the pigment. The PSP is increasing when oxygen is admitted. Water vapour does not increase the PSP of the adsorbed chlorophyll a. It has been supposed that the ESR signal of chlorophyll a in solution belongs to the chlorophyll-oxygen complex and that any strengthening of the pi-pi-interactions results in intensification of the ESR signal. It has been concluded that the ESR signal of adsorbed chlorophyll a belongs to the charge transfer complex of the molecular oxygen and the chlorophyll aggregate with strong pi-pi-interactions.", "contents": "[ESR of adsorbed chlorophyll a]. Oxygen and water vapour effect on the dark ESR signal of chlorophyll a adsorbed on silica in vacuum has been studied. It has been determined that when O2 and H2O are absent chlorophyll a adsorption is accompanied by an increase of the paramagnetic states portion (PSP) of the pigment. The PSP is increasing when oxygen is admitted. Water vapour does not increase the PSP of the adsorbed chlorophyll a. It has been supposed that the ESR signal of chlorophyll a in solution belongs to the chlorophyll-oxygen complex and that any strengthening of the pi-pi-interactions results in intensification of the ESR signal. It has been concluded that the ESR signal of adsorbed chlorophyll a belongs to the charge transfer complex of the molecular oxygen and the chlorophyll aggregate with strong pi-pi-interactions."}
{"id": "PMID:224951", "title": "[Effect of inhibitors of free radical processes on the \"dark\" paramagnetic centers of the melanoprotein granules of the pigment epithelium of the eye].", "content": "Effect of three inhibitors of free radical processes (IFRP) differing in antiradical activity (2-tret. butyl-6-methyl-3-oxipyridin, 2-ethyl-6-methyl-3-oxipyridin and 3-oxipyridin) on paramagnetic centres of melanoprotein granules of pigment epithelium was studied by ESR method at room temperature. It was shown that IFRP decreased the dark signal and that the reaction of paramagnetic particles dissociation proceeded according to the equation of the first order reaction. The rate constants of these reactions were calculated. It was found that the relative amount of reacting and non-reacting paramagnetic particles with the inhibitor depended on the nature and concentration of IFRP.", "contents": "[Effect of inhibitors of free radical processes on the \"dark\" paramagnetic centers of the melanoprotein granules of the pigment epithelium of the eye]. Effect of three inhibitors of free radical processes (IFRP) differing in antiradical activity (2-tret. butyl-6-methyl-3-oxipyridin, 2-ethyl-6-methyl-3-oxipyridin and 3-oxipyridin) on paramagnetic centres of melanoprotein granules of pigment epithelium was studied by ESR method at room temperature. It was shown that IFRP decreased the dark signal and that the reaction of paramagnetic particles dissociation proceeded according to the equation of the first order reaction. The rate constants of these reactions were calculated. It was found that the relative amount of reacting and non-reacting paramagnetic particles with the inhibitor depended on the nature and concentration of IFRP."}
{"id": "PMID:224956", "title": "Postnatal changes in carbamylphosphate synthetase-I and ornithine transcarbamylase activities after normal birth, premature delivery and prolonged gestation in rat liver: effects of actinomycin D and glucose.", "content": "The development of two urea cycle enzymes, carbamylphosphate synthetase-I and ornithine transcarbamylase was examined in neonatal rat liver. Normal birth on day 21.5 caused a marked increase of both activities as early as 4 h of extrauterine life. That increase occurred later in newborns delivered by cesarian section on day 21.5, but they exhibited a greater hepatic urea level. Premature delivery on day 20.5 caused a marked increase of both activities and hepatic urea level while prolonged gestation abolished these increases. The postnatal increase in both activities and in hepatic urea level was therefore dependent on a factor associated with birth. The in vivo administration of actinomycin D (2 microgram) at birth did not abolish the postnatal increase of both activities. Moreover, the administration of glucose (25 mg every 2 h) to newborns delivered by cesarian section on day 21.5 abolished the postnatal increase of ornithine transcarbamylase activity and hepatic urea level 23 h later. It seems that the transient hypoglycemia and appearance of gluconeogenesis at birth were the physiological mechanisms involved in the postnatal induction of ornithine transcarbamylase activity.", "contents": "Postnatal changes in carbamylphosphate synthetase-I and ornithine transcarbamylase activities after normal birth, premature delivery and prolonged gestation in rat liver: effects of actinomycin D and glucose. The development of two urea cycle enzymes, carbamylphosphate synthetase-I and ornithine transcarbamylase was examined in neonatal rat liver. Normal birth on day 21.5 caused a marked increase of both activities as early as 4 h of extrauterine life. That increase occurred later in newborns delivered by cesarian section on day 21.5, but they exhibited a greater hepatic urea level. Premature delivery on day 20.5 caused a marked increase of both activities and hepatic urea level while prolonged gestation abolished these increases. The postnatal increase in both activities and in hepatic urea level was therefore dependent on a factor associated with birth. The in vivo administration of actinomycin D (2 microgram) at birth did not abolish the postnatal increase of both activities. Moreover, the administration of glucose (25 mg every 2 h) to newborns delivered by cesarian section on day 21.5 abolished the postnatal increase of ornithine transcarbamylase activity and hepatic urea level 23 h later. It seems that the transient hypoglycemia and appearance of gluconeogenesis at birth were the physiological mechanisms involved in the postnatal induction of ornithine transcarbamylase activity."}
{"id": "PMID:224952", "title": "[Formation of nitrosyl complexes of nonheme iron (2.03 complexes) in animal tissues in vivo].", "content": "Formation or dinitrozyl non-haem iron complexes (2.03 complexes) in white rats' tissues in vivo has been studied. The formation of these complexes has been examined in the liver kidneys and small intestines when injecting p/o NaNO2 to the rats. Most of the complexes have been found in the liver. They have not been detected in the heart, spleen, muscle, cerebrum and marrow in vivo. 3-4-fold content of 2.03 complexes has been determined while introducing iron and NaNO2 in running water. This effect has not been found when introducing iron and NaNO2 simultaneously. The mechanism of 2.03 complex formation in the animal tissues in vivo has been proposed. According to this mechanism these complexes are formed in the tissues when Fe-NO from nitrozyl non-haem from complexes originating in blood passes into SH-group of protein in tissues. The formation of 2.03 complexes in vivo has been found in blood uniform elements.", "contents": "[Formation of nitrosyl complexes of nonheme iron (2.03 complexes) in animal tissues in vivo]. Formation or dinitrozyl non-haem iron complexes (2.03 complexes) in white rats' tissues in vivo has been studied. The formation of these complexes has been examined in the liver kidneys and small intestines when injecting p/o NaNO2 to the rats. Most of the complexes have been found in the liver. They have not been detected in the heart, spleen, muscle, cerebrum and marrow in vivo. 3-4-fold content of 2.03 complexes has been determined while introducing iron and NaNO2 in running water. This effect has not been found when introducing iron and NaNO2 simultaneously. The mechanism of 2.03 complex formation in the animal tissues in vivo has been proposed. According to this mechanism these complexes are formed in the tissues when Fe-NO from nitrozyl non-haem from complexes originating in blood passes into SH-group of protein in tissues. The formation of 2.03 complexes in vivo has been found in blood uniform elements."}
{"id": "PMID:224953", "title": "[Free radical centers in the chromatophores and preparations of Rhodospirillum rubrum reaction centers].", "content": "The light-induced free radical ESR signals in chromatophores and reaction center preparation of R. rubrum were studied. It has been shown that the properties of the signals in both systems were strictly identical. At the microwave powers higher than 10 mW the ESR signal at g approximatley 2.00 is saturated and its asymmetry arises. Changes of the ESR signal shape may be explained by the superposition of P870+ signal with that from the ubisemiquinone. Addition of ferricyanide to chromatophores induces in the dark a new ESR signal characterized by a linewidth of 4.5 Oe which presumably arises from the antenna bacteriochlorophyll aggregates, because this signal is absent in the reaction center preparations.", "contents": "[Free radical centers in the chromatophores and preparations of Rhodospirillum rubrum reaction centers]. The light-induced free radical ESR signals in chromatophores and reaction center preparation of R. rubrum were studied. It has been shown that the properties of the signals in both systems were strictly identical. At the microwave powers higher than 10 mW the ESR signal at g approximatley 2.00 is saturated and its asymmetry arises. Changes of the ESR signal shape may be explained by the superposition of P870+ signal with that from the ubisemiquinone. Addition of ferricyanide to chromatophores induces in the dark a new ESR signal characterized by a linewidth of 4.5 Oe which presumably arises from the antenna bacteriochlorophyll aggregates, because this signal is absent in the reaction center preparations."}
{"id": "PMID:224957", "title": "Perinatal development of glucoeneogenic enzymes in rabbit liver.", "content": "Activities of the 4 hepatic gluconeogenic enzymes: glucose-6-phosphatase, fructose-1,6-diphosphatase, pyruvate carboxylase, particulate and cytosolic phosphoenolpyruvate carboxykinase (PEPCK) have been measured in fetal rabbits (22, 25, 28, 30 and 31 days of gestation) and in fasted or suckling newborns (1 and 2 days after birth). Between days 25 and 31 of gestation, fructose 1,6-diphosphatase and particulate PEPCK activities represent 50% of adult (pregnant female) activities, while pyruvate carboxylase is present at adult values during the same period. Glucose-6-phosphatase is low and cytosolic PEPCK absent in fetal liver until 30 days of gestation and increase significantly during the day preceding birth. Al the enzymes show a further increase after birth independently of the nutritional status of the animals (starved or suckling).", "contents": "Perinatal development of glucoeneogenic enzymes in rabbit liver. Activities of the 4 hepatic gluconeogenic enzymes: glucose-6-phosphatase, fructose-1,6-diphosphatase, pyruvate carboxylase, particulate and cytosolic phosphoenolpyruvate carboxykinase (PEPCK) have been measured in fetal rabbits (22, 25, 28, 30 and 31 days of gestation) and in fasted or suckling newborns (1 and 2 days after birth). Between days 25 and 31 of gestation, fructose 1,6-diphosphatase and particulate PEPCK activities represent 50% of adult (pregnant female) activities, while pyruvate carboxylase is present at adult values during the same period. Glucose-6-phosphatase is low and cytosolic PEPCK absent in fetal liver until 30 days of gestation and increase significantly during the day preceding birth. Al the enzymes show a further increase after birth independently of the nutritional status of the animals (starved or suckling)."}
{"id": "PMID:224958", "title": "The effect of fluphenazine upon social and vocational functioning in remitted schizophrenics.", "content": "Thirty-six remitted schizophrenics who participated in an outpatient study of fluphenazine decanoate or oral fluphenazine vs placebo given for a year were examined for the effect of drug treatment upon social and vocational functioning. Only the period prior to any clinical relapse was evaluated. We found no difference between those on drug or placebo, and conclude that antipsychotic drugs, at least in the context of an aftercare clinic offering a rich spectrum of nonpharmacological services, and when combined with antiparkinson medication, do not interfere with social and vocational functioning.", "contents": "The effect of fluphenazine upon social and vocational functioning in remitted schizophrenics. Thirty-six remitted schizophrenics who participated in an outpatient study of fluphenazine decanoate or oral fluphenazine vs placebo given for a year were examined for the effect of drug treatment upon social and vocational functioning. Only the period prior to any clinical relapse was evaluated. We found no difference between those on drug or placebo, and conclude that antipsychotic drugs, at least in the context of an aftercare clinic offering a rich spectrum of nonpharmacological services, and when combined with antiparkinson medication, do not interfere with social and vocational functioning."}
{"id": "PMID:224955", "title": "Antibacterial effect of some combinations of pesticides of pure cultures of microorganisms.", "content": "The investigations conducted showed that the antibacterial effect of dinitro-o-cresol, cuprozane, and trichlorfon is due to their chemical structure and to the species of microorganisms on which they act. Dinitro-o-cresol and Cuprozane possess selective toxicity with respect to B. anthracis and Rh. gracilis and cuprozane with respect to Ch. perfringens. The method of evaluating the effect of combinations of chemical compounds consisting of two or more components which have been developed made it possible to detect the antibacterial effect of mixtures consisting of the indicated pesticides. It was established that the combinations studied possess synergic and additive effects, which also depend on the chemical structure of the pesticides and the species of microorganisms.", "contents": "Antibacterial effect of some combinations of pesticides of pure cultures of microorganisms. The investigations conducted showed that the antibacterial effect of dinitro-o-cresol, cuprozane, and trichlorfon is due to their chemical structure and to the species of microorganisms on which they act. Dinitro-o-cresol and Cuprozane possess selective toxicity with respect to B. anthracis and Rh. gracilis and cuprozane with respect to Ch. perfringens. The method of evaluating the effect of combinations of chemical compounds consisting of two or more components which have been developed made it possible to detect the antibacterial effect of mixtures consisting of the indicated pesticides. It was established that the combinations studied possess synergic and additive effects, which also depend on the chemical structure of the pesticides and the species of microorganisms."}
{"id": "PMID:224964", "title": "In vitro transforming activity of Epstein-Barr virus (EBV). II. Differences between M81 and B95-8 EBV strains.", "content": "Lymphocytes from 38 human cord blood and 9 adult circulating blood were aliquoted and infected in parallel either with the B95-8 EBV strain (produced by cotton-top marmoset lymphocytes transformed by EBV originating from an infectious mononucleosis line) or with the M81 EB virus (produced by callithrix jacchus marmoset lymphocytes transformed by EBV originating from a nasopharyngeal carcinoma (NPC) derived line). Significant differences were observed in the lymphoblastoid lines obtained and involved cell morphology, cell growth and synthesis of viral antigen. Cord blood lymphocytes infected with M81 virus resulted in lymphoblastoid lines where EA and VCA synthesis and production of virions took place, whereas this was not observed in B95-8 induced lines.", "contents": "In vitro transforming activity of Epstein-Barr virus (EBV). II. Differences between M81 and B95-8 EBV strains. Lymphocytes from 38 human cord blood and 9 adult circulating blood were aliquoted and infected in parallel either with the B95-8 EBV strain (produced by cotton-top marmoset lymphocytes transformed by EBV originating from an infectious mononucleosis line) or with the M81 EB virus (produced by callithrix jacchus marmoset lymphocytes transformed by EBV originating from a nasopharyngeal carcinoma (NPC) derived line). Significant differences were observed in the lymphoblastoid lines obtained and involved cell morphology, cell growth and synthesis of viral antigen. Cord blood lymphocytes infected with M81 virus resulted in lymphoblastoid lines where EA and VCA synthesis and production of virions took place, whereas this was not observed in B95-8 induced lines."}
{"id": "PMID:224965", "title": "Chemotaxis of human leucocytes: II. Effects of lectins, colchicine, cytochalasin B, cyclic nucleotides and immuno-stimulatory products.", "content": "Drugs or products acting as chemo-modulators were assayed for their effect on the chemotactic activity of human normal neutrophils by a method of direct microscopic observation. Lectins (PHA-P and Con A) have an inhibitory effect at the level of 10 micrograms/ml. Colchicine and Cytochalasin B have also an inhibitory effect at the level of 0.25.10(-6)M/ml and 0.20 micrograms/ml. For the cyclic nucleotides: dibutyryl cAMP and products such as norepinephrine, aminophylline that raise the cellular level of cAMP have an inhibitory effect, and whereas cGMP and carbamylcholine have a stimulatory effect Imidazole and levamisole, have some enhancement of chemotaxis but it is not significant. Lectins by binding to cell surface receptors which assume the recognition of a chemotactic gradient in the environment, colchicine and cytochalasin B by interfering with the cytoskeletal elements (microtubules and microfilaments) cyclic nucleotides involved in the metabolic activity during the cell motility. The data show that the integrity of one of these three sequences is necessary for the normal activity of chemotasxis. Animal and human models (i.e. mutant mouse bg/bg and Chediak-Higashi syndrome) give some clue of their interrelation.", "contents": "Chemotaxis of human leucocytes: II. Effects of lectins, colchicine, cytochalasin B, cyclic nucleotides and immuno-stimulatory products. Drugs or products acting as chemo-modulators were assayed for their effect on the chemotactic activity of human normal neutrophils by a method of direct microscopic observation. Lectins (PHA-P and Con A) have an inhibitory effect at the level of 10 micrograms/ml. Colchicine and Cytochalasin B have also an inhibitory effect at the level of 0.25.10(-6)M/ml and 0.20 micrograms/ml. For the cyclic nucleotides: dibutyryl cAMP and products such as norepinephrine, aminophylline that raise the cellular level of cAMP have an inhibitory effect, and whereas cGMP and carbamylcholine have a stimulatory effect Imidazole and levamisole, have some enhancement of chemotaxis but it is not significant. Lectins by binding to cell surface receptors which assume the recognition of a chemotactic gradient in the environment, colchicine and cytochalasin B by interfering with the cytoskeletal elements (microtubules and microfilaments) cyclic nucleotides involved in the metabolic activity during the cell motility. The data show that the integrity of one of these three sequences is necessary for the normal activity of chemotasxis. Animal and human models (i.e. mutant mouse bg/bg and Chediak-Higashi syndrome) give some clue of their interrelation."}
{"id": "PMID:224966", "title": "Virus induced diabetes and the immune system. II -- Evidence for an immune pathogenesis of the acute phase of diabetes.", "content": "The infection of normal DBA2 and BALB/C nu/ + mice with 2 X 10(2,6) TCID50 of the M variant of the EMC virus induced pathological mean glucose values of 426 +/- 99 mg/100 ml in DBA2 mice and 292 +/- 130 mg/100 ml in BALB/C nu/ + mice on day five following infection. As diabetic animals died afterwards, mean glucose values decreased in the surviving animals on day seven and fourteen. The infected immunodeficient BALB/C nu/nu mice with thymus aplasia did not show abnormal mean glucose values or higher standard deviation of the means (114 +/- 37 mg/100 ml) when compared to uninfected controls (117 +/- 23 mg/100 ml). This demonstrates that a complete thymus-dependent immune system seems to be necessary for the development of the acute stage of virus-induced diabetes in the mouse.", "contents": "Virus induced diabetes and the immune system. II -- Evidence for an immune pathogenesis of the acute phase of diabetes. The infection of normal DBA2 and BALB/C nu/ + mice with 2 X 10(2,6) TCID50 of the M variant of the EMC virus induced pathological mean glucose values of 426 +/- 99 mg/100 ml in DBA2 mice and 292 +/- 130 mg/100 ml in BALB/C nu/ + mice on day five following infection. As diabetic animals died afterwards, mean glucose values decreased in the surviving animals on day seven and fourteen. The infected immunodeficient BALB/C nu/nu mice with thymus aplasia did not show abnormal mean glucose values or higher standard deviation of the means (114 +/- 37 mg/100 ml) when compared to uninfected controls (117 +/- 23 mg/100 ml). This demonstrates that a complete thymus-dependent immune system seems to be necessary for the development of the acute stage of virus-induced diabetes in the mouse."}
{"id": "PMID:224967", "title": "Hepatitis A infection and primary hepatocellular carcinoma.", "content": "The prevalence of antibody to the hepatitis A antigen (anti-HAV) has been studied in Senegal, among patients suffering from primary hepatocellular carcinoma (PHC) and among healthy blood donors. Anti-HAV was found in 62.5% of 64 cases of PHC as compared to 64% of 50 blood donors. Anti-HAV was as prevalent among PHC patients who evidenced chronic hepatitis B infection as among those without markers of chronic hepatitis B infection. These data suggest that hepatitis A infection is not associated with PHC in Senegal.", "contents": "Hepatitis A infection and primary hepatocellular carcinoma. The prevalence of antibody to the hepatitis A antigen (anti-HAV) has been studied in Senegal, among patients suffering from primary hepatocellular carcinoma (PHC) and among healthy blood donors. Anti-HAV was found in 62.5% of 64 cases of PHC as compared to 64% of 50 blood donors. Anti-HAV was as prevalent among PHC patients who evidenced chronic hepatitis B infection as among those without markers of chronic hepatitis B infection. These data suggest that hepatitis A infection is not associated with PHC in Senegal."}
{"id": "PMID:224968", "title": "Abnormal red cell membrane phosphatase activity in an unidentified congenital hemolytic anemia.", "content": "The erythrocyte membrane contains a neutral phosphatase, which was studied with p-nitrophenyl-phosphate as the substrate. The enzyme was investigated in four members of the same family, suffering from a congenital spherocytic hemolytic anemia. Although the condition was transmitted as a dominant trait, it was not identified to the common hereditary spherocytosis. The phosphatase, instead of having a Michaelis-Menten kinetics, displayed a dramatically biphasic kinetics: substrate excess generated partial inhibition of the enzyme. We consider that such an abnormality, which was never encountered before, is a distinctive feature of a given type of congenital hemolytic anemia.", "contents": "Abnormal red cell membrane phosphatase activity in an unidentified congenital hemolytic anemia. The erythrocyte membrane contains a neutral phosphatase, which was studied with p-nitrophenyl-phosphate as the substrate. The enzyme was investigated in four members of the same family, suffering from a congenital spherocytic hemolytic anemia. Although the condition was transmitted as a dominant trait, it was not identified to the common hereditary spherocytosis. The phosphatase, instead of having a Michaelis-Menten kinetics, displayed a dramatically biphasic kinetics: substrate excess generated partial inhibition of the enzyme. We consider that such an abnormality, which was never encountered before, is a distinctive feature of a given type of congenital hemolytic anemia."}
{"id": "PMID:224970", "title": "Electron spin resonance (esr) investigations on blood of patients with leukemia.", "content": "ESR investigations of lyophilized blood of patients with acute lymphatic leukemia exhibit an increase in spin concentration and an additional peak not present in control samples. This peak disappears almost completely concomittantly with a reduction in spin concentration after treating the patients with prednisolone, vincristine, and doxorubicin or after addition of 5mM of CuCl2 to blood samples. The results show that the ESR spectra of lyophilized blood samples can be utilized to follow the effect of therapy. Moreover, they suggest that the leukemic blood possesses a high concentration of antioxidants.", "contents": "Electron spin resonance (esr) investigations on blood of patients with leukemia. ESR investigations of lyophilized blood of patients with acute lymphatic leukemia exhibit an increase in spin concentration and an additional peak not present in control samples. This peak disappears almost completely concomittantly with a reduction in spin concentration after treating the patients with prednisolone, vincristine, and doxorubicin or after addition of 5mM of CuCl2 to blood samples. The results show that the ESR spectra of lyophilized blood samples can be utilized to follow the effect of therapy. Moreover, they suggest that the leukemic blood possesses a high concentration of antioxidants."}
{"id": "PMID:224971", "title": "Lithium side effects in a routine lithium clinic.", "content": "Approximately two thirds of a group of bipolar patients attending the routine lithium clinic suffered sid effects. These patients tended to have a lower plasma and erythrocyte lithium concentration and a lower erythrocyte/plasma lithium ratio than those who had no side effects. Explanations of this unexpected finding are discussed.", "contents": "Lithium side effects in a routine lithium clinic. Approximately two thirds of a group of bipolar patients attending the routine lithium clinic suffered sid effects. These patients tended to have a lower plasma and erythrocyte lithium concentration and a lower erythrocyte/plasma lithium ratio than those who had no side effects. Explanations of this unexpected finding are discussed."}
{"id": "PMID:224973", "title": "The antidromic compound action potential of the hypothalamo-neurohypophysial tract, a tool for assessing posterior pituitary activity in vivo.", "content": "A sensitive technique was developed for measuring continuously the summated neural activity of the rat hypothalamo-neurohypophysial tract. Large compound potentials of 4-9 mV peak amplitude were recorded from the fibre tract in response to electrical stimulation of the neurohypophysis. It was estimated that all fibres in the tract were electrically activated and contributed to the compound potential. It was shown that a decrease of peak amplitude could be used as a measure of changes in endogenous neural activity. The decrease in peak amplitude during an increase of endogenous neural activity was due to fatigue and temporal spread of the compound potential, and also to collision of antidromic and orthodromic action potentials. Decrease of the compound potentials was related to the intensity of vaginal distension, haemorrhage and plasma hyperosmolality, and it correlated with neurohypophysial hormone release. This method may usefully complement hormone assays and single cell analysis.", "contents": "The antidromic compound action potential of the hypothalamo-neurohypophysial tract, a tool for assessing posterior pituitary activity in vivo. A sensitive technique was developed for measuring continuously the summated neural activity of the rat hypothalamo-neurohypophysial tract. Large compound potentials of 4-9 mV peak amplitude were recorded from the fibre tract in response to electrical stimulation of the neurohypophysis. It was estimated that all fibres in the tract were electrically activated and contributed to the compound potential. It was shown that a decrease of peak amplitude could be used as a measure of changes in endogenous neural activity. The decrease in peak amplitude during an increase of endogenous neural activity was due to fatigue and temporal spread of the compound potential, and also to collision of antidromic and orthodromic action potentials. Decrease of the compound potentials was related to the intensity of vaginal distension, haemorrhage and plasma hyperosmolality, and it correlated with neurohypophysial hormone release. This method may usefully complement hormone assays and single cell analysis."}
{"id": "PMID:224974", "title": "Behavioral and biochemical analysis of GABA-mediated inhibition in the early chick embryo.", "content": "Exogenous gamma-aminobutyric acid (GABA) decreased spontaneous motility in 4-, 6-, 7-, 9-, and 13-day chick embryos; the younger embryos were more sensitive. Neither the positional isomers of GABA, alpha-aminobutyric acid (AABA) and beta-aminobutyric acid, nor the principle GABA catabolite, succinic acid, decreased motility in 4-day embryos. Several semi-rigid GABA analogues decreased motility in 4-day embryos with a potency that paralleled their effectiveness in displacing [3H]GABA in ligand-binding studies. The effects of AABA and GABA on hind-limb motility were quantitatively similar in thoracic spinal and sham-operated 7-day embryos. Bicuculline and picrotoxin elicited absolute motility increases at 6, 7 and 9 days of incubation. Picrotoxin and two bicyclophosphate GABA antagnoists elicited relative motility increases while bicuculline elicited an absolute motility increase at 4 days. The two bicyclophosphates increased motility with a potency that paralleled their electrophysiological effectiveness. L-Glutamic acid decarboxylase (GAD) activity was detected in the embryonic lumbar spinal cord at all ages examined (3--7 days) using a new radiometric cation-exchange method. Gamma-Aminobutyric acid transaminase (GABA-T) activity was detected in the lumbar spinal cord at the earliest age examined (day 5). Both GAD and GABA-T activity were detected at earlier ages than previously reported. GABA receptors, and the enzymes necessary for the synthesis and degradation of GABA, all appear to be present at (or before) the onset of spontaneous motility. GABA-mediated transmission appears to be present at 6 days and perhaps as early as 4 days.", "contents": "Behavioral and biochemical analysis of GABA-mediated inhibition in the early chick embryo. Exogenous gamma-aminobutyric acid (GABA) decreased spontaneous motility in 4-, 6-, 7-, 9-, and 13-day chick embryos; the younger embryos were more sensitive. Neither the positional isomers of GABA, alpha-aminobutyric acid (AABA) and beta-aminobutyric acid, nor the principle GABA catabolite, succinic acid, decreased motility in 4-day embryos. Several semi-rigid GABA analogues decreased motility in 4-day embryos with a potency that paralleled their effectiveness in displacing [3H]GABA in ligand-binding studies. The effects of AABA and GABA on hind-limb motility were quantitatively similar in thoracic spinal and sham-operated 7-day embryos. Bicuculline and picrotoxin elicited absolute motility increases at 6, 7 and 9 days of incubation. Picrotoxin and two bicyclophosphate GABA antagnoists elicited relative motility increases while bicuculline elicited an absolute motility increase at 4 days. The two bicyclophosphates increased motility with a potency that paralleled their electrophysiological effectiveness. L-Glutamic acid decarboxylase (GAD) activity was detected in the embryonic lumbar spinal cord at all ages examined (3--7 days) using a new radiometric cation-exchange method. Gamma-Aminobutyric acid transaminase (GABA-T) activity was detected in the lumbar spinal cord at the earliest age examined (day 5). Both GAD and GABA-T activity were detected at earlier ages than previously reported. GABA receptors, and the enzymes necessary for the synthesis and degradation of GABA, all appear to be present at (or before) the onset of spontaneous motility. GABA-mediated transmission appears to be present at 6 days and perhaps as early as 4 days."}
{"id": "PMID:224981", "title": "Evaluation of receptor function in ACTH-responsive and ACTH-insensitive adrenal tumor cells.", "content": "Two variant cell lines (Y6 and OS3), derived from the ACTH-sensitive mouse adrenocortical tumor clone Y1, are defective in the ACTH-sensitive adenylate cyclase system. This study further characterizes the nature of the defects in Y6 and OS3 cells using ACTH1-10, ACTH4-10, and cholera toxin. In Y1 cells, ACTH1-39, ACTH1-10, and ACTH4-10 stimulated steroidogenesis to the same maximum level with Kd' values of 5 x 10(-11) M, 5 x 10(-7) M and 10(-4) m respectively. ACTH1-10 (0.4 mM) and ACTH4-10 (3.2 mM) increased the accumulation of adenosine 3',5'-monophosphate (cAMP) in Y1 cells two- to three-fold. Cholera toxin increased steroidogenesis and cAMP accumulation in Y1 cells with Kd' values of 0.4 ng/mL and 9 ng/mL respectively. Y6 and OS3 cells responded to added cholera toxin with increased cAMP accumulation and increased steroidogenesis but did not respond to ACTH1-39, ACTH1-10, or ACTH4-10 at concentrations effective in Y1 cells. These data are interpreted to suggest that Y6 and OS3 cells are defective in a process or component that links the principal binding regions of the ACTH receptor to the catalytic subunit of the adenylate cyclase system. Attempts to were made to assess the interactions of ACTH with the principal binding regions of the ACTH receptor by analysis of binding of radioactive, iodinated ACTH1-24. ACTH binding, however, showed low affinity, high capacity, and no target-tissue specificity, and was considered not to be useful in evaluating the integrity of the ACTH receptor.", "contents": "Evaluation of receptor function in ACTH-responsive and ACTH-insensitive adrenal tumor cells. Two variant cell lines (Y6 and OS3), derived from the ACTH-sensitive mouse adrenocortical tumor clone Y1, are defective in the ACTH-sensitive adenylate cyclase system. This study further characterizes the nature of the defects in Y6 and OS3 cells using ACTH1-10, ACTH4-10, and cholera toxin. In Y1 cells, ACTH1-39, ACTH1-10, and ACTH4-10 stimulated steroidogenesis to the same maximum level with Kd' values of 5 x 10(-11) M, 5 x 10(-7) M and 10(-4) m respectively. ACTH1-10 (0.4 mM) and ACTH4-10 (3.2 mM) increased the accumulation of adenosine 3',5'-monophosphate (cAMP) in Y1 cells two- to three-fold. Cholera toxin increased steroidogenesis and cAMP accumulation in Y1 cells with Kd' values of 0.4 ng/mL and 9 ng/mL respectively. Y6 and OS3 cells responded to added cholera toxin with increased cAMP accumulation and increased steroidogenesis but did not respond to ACTH1-39, ACTH1-10, or ACTH4-10 at concentrations effective in Y1 cells. These data are interpreted to suggest that Y6 and OS3 cells are defective in a process or component that links the principal binding regions of the ACTH receptor to the catalytic subunit of the adenylate cyclase system. Attempts to were made to assess the interactions of ACTH with the principal binding regions of the ACTH receptor by analysis of binding of radioactive, iodinated ACTH1-24. ACTH binding, however, showed low affinity, high capacity, and no target-tissue specificity, and was considered not to be useful in evaluating the integrity of the ACTH receptor."}
{"id": "PMID:224983", "title": "Low density lipoprotein binding, internalization, and degradation in human adipose cells.", "content": "Human adipose tissue derives its cholesterol primarily from circulating lipoproteins. To study fat cell-lipoprotein interactions, low density lipoprotein (LDL) uptake and metabolism were examined using isolated human adipocytes. The 125I-labelled LDL (d = 1.025-1.045) was bound and incorporated by human fat cells in a dose-dependent manner with an apparent Km of 6.9 + 0.9 microgram LDL protein/mL and a Vmax of 15-80 microgram LDL protein/mg lipid per 2 h. In time-course studies, LDL uptake was characterized by rapid initial binding followed by a linear accumulation for at least 4 h. The 125I-labelled LDL degradation products (trichloroacetic acid soluble iodopeptides) accumulated in the incubation medium in a progressive manner with time. Azide and F- inhibited LDL internalization and degradation, suggesting that these processes are energy dependent. Binding and cellular internalization of 125I-labelled LDL lacked lipoprotein class specificity in that excess (25-fold) unlabelled very low density lipoprotein (VLDL) (d less than 1.006) and high density lipoprotein (HDL) (d = 1.075-1.21) inhibited binding and internalization of 125I-labelled LDL. On an equivalent protein basis HDL was the most potent. The 125I-labelled LDL binding to an adipocyte plasma membrane preparation was a saturable process and almost completely abolished by a three- to four-fold greater concentration of HDL. The binding, internalization, and degradation of LDL by human adipocytes resembled that reported by other mesenchymal cells and could account for a significant proportion of in vivo LDL catabolism. It is further suggested that adipose tissue is an important site of LDL and HDL interactions.", "contents": "Low density lipoprotein binding, internalization, and degradation in human adipose cells. Human adipose tissue derives its cholesterol primarily from circulating lipoproteins. To study fat cell-lipoprotein interactions, low density lipoprotein (LDL) uptake and metabolism were examined using isolated human adipocytes. The 125I-labelled LDL (d = 1.025-1.045) was bound and incorporated by human fat cells in a dose-dependent manner with an apparent Km of 6.9 + 0.9 microgram LDL protein/mL and a Vmax of 15-80 microgram LDL protein/mg lipid per 2 h. In time-course studies, LDL uptake was characterized by rapid initial binding followed by a linear accumulation for at least 4 h. The 125I-labelled LDL degradation products (trichloroacetic acid soluble iodopeptides) accumulated in the incubation medium in a progressive manner with time. Azide and F- inhibited LDL internalization and degradation, suggesting that these processes are energy dependent. Binding and cellular internalization of 125I-labelled LDL lacked lipoprotein class specificity in that excess (25-fold) unlabelled very low density lipoprotein (VLDL) (d less than 1.006) and high density lipoprotein (HDL) (d = 1.075-1.21) inhibited binding and internalization of 125I-labelled LDL. On an equivalent protein basis HDL was the most potent. The 125I-labelled LDL binding to an adipocyte plasma membrane preparation was a saturable process and almost completely abolished by a three- to four-fold greater concentration of HDL. The binding, internalization, and degradation of LDL by human adipocytes resembled that reported by other mesenchymal cells and could account for a significant proportion of in vivo LDL catabolism. It is further suggested that adipose tissue is an important site of LDL and HDL interactions."}
{"id": "PMID:224984", "title": "An approach to measuring the in vivo transformation of glycerol to a very low density lipoprotein triglyceride.", "content": "This paper describes a new method which permits measurement of the steady-state rate of transformation of serum glycerol to a very low density lipoprotein (VLDL) triglyceride in vivo in dogs. Although the turnover of glycerol and the turnover of VLDL triglyceride glycerol have both been previously measured, the rate of transformation of the former into the latter has not. While there is considerable dog-to-dog variation in the absolute turnover and transformation rates, the relationship between the various rates is quite constant. Thus, 13% of the serum glycerol which normal fasting dogs utilize is converted to VLDL triglyceride. The remaining 87% is converted to other products. Also, 28% of VLDL triglyceride glycerol in these dogs is derived from serum glycerol. The balance, 72%, is derived from other sources. The procedure described here can be used to quantitate the contribution of glycerol to VLDL in a number of conditions in which glycerol and (or) VLDL triglyceride metabolism is altered, thereby providing another way to gain insight into the metabolism of VLDL. Even more generally, the principles developed here can be applied to estimate the transformation of other precursors to other products in vivo.", "contents": "An approach to measuring the in vivo transformation of glycerol to a very low density lipoprotein triglyceride. This paper describes a new method which permits measurement of the steady-state rate of transformation of serum glycerol to a very low density lipoprotein (VLDL) triglyceride in vivo in dogs. Although the turnover of glycerol and the turnover of VLDL triglyceride glycerol have both been previously measured, the rate of transformation of the former into the latter has not. While there is considerable dog-to-dog variation in the absolute turnover and transformation rates, the relationship between the various rates is quite constant. Thus, 13% of the serum glycerol which normal fasting dogs utilize is converted to VLDL triglyceride. The remaining 87% is converted to other products. Also, 28% of VLDL triglyceride glycerol in these dogs is derived from serum glycerol. The balance, 72%, is derived from other sources. The procedure described here can be used to quantitate the contribution of glycerol to VLDL in a number of conditions in which glycerol and (or) VLDL triglyceride metabolism is altered, thereby providing another way to gain insight into the metabolism of VLDL. Even more generally, the principles developed here can be applied to estimate the transformation of other precursors to other products in vivo."}
{"id": "PMID:224986", "title": "Multiple effects of serum low-density lipoprotein on cultured human fibroblasts.", "content": "The effects of serum low-density lipoproteins (LDL) were studied in cultures of human skin fibroblasts grown in medium supplemented with human serum deficient in lipoproteins and in platelet factor. The LDL led to a temporary increase in the rate of cell replication, to increases in the cell content of protein and cholesterol, to an increase in average cell size, and to an increased secretion of glycosaminoglycans. The increases in cholesterol and protein were proportional to the increase in cell size, suggesting that the additional protein and cholesterol were of a structural, rather than a storage, nature. The increase in cell protein during the first few days of exposure to LDL was due to a decrease in the rate of protein degradation. Ultrafiltration of the serum to remove substances of molecular weight less than 30,000 did not reduce the basal rate of cell proliferation but did prevent the stimulation of proliferation by LDL; it did not alter the effect of LDL on cell protein and cholesterol, indicating that the latter responses are independent of the mitogenic action. The response of cells from diabetic donors did not differ from that of normal cells.", "contents": "Multiple effects of serum low-density lipoprotein on cultured human fibroblasts. The effects of serum low-density lipoproteins (LDL) were studied in cultures of human skin fibroblasts grown in medium supplemented with human serum deficient in lipoproteins and in platelet factor. The LDL led to a temporary increase in the rate of cell replication, to increases in the cell content of protein and cholesterol, to an increase in average cell size, and to an increased secretion of glycosaminoglycans. The increases in cholesterol and protein were proportional to the increase in cell size, suggesting that the additional protein and cholesterol were of a structural, rather than a storage, nature. The increase in cell protein during the first few days of exposure to LDL was due to a decrease in the rate of protein degradation. Ultrafiltration of the serum to remove substances of molecular weight less than 30,000 did not reduce the basal rate of cell proliferation but did prevent the stimulation of proliferation by LDL; it did not alter the effect of LDL on cell protein and cholesterol, indicating that the latter responses are independent of the mitogenic action. The response of cells from diabetic donors did not differ from that of normal cells."}
{"id": "PMID:224988", "title": "Presence of herpes simplex virus type 2 DNA in hamster cells oncogenically transformed by ultraviolet-inactivated virus.", "content": "Herpes simplex virus type 2 (HSV-2) DNA has been detected by molecular hybridization in hamster fibroblast cells oncogenically transformed by ultraviolet-irradiated virus. At early passages after cloning in soft agar, about 40% of the HSV-2 genome was present in all the transformed cell lines at one to six copies per cell. In cell lines derived from tumors induced by these cells, the same percentage of the HSV-2 genome was also found with more uniform number of copies (between two and three). Thus the presence of viral DNA seems to be necessary for the maintenance of the transformed state in these cell lines.", "contents": "Presence of herpes simplex virus type 2 DNA in hamster cells oncogenically transformed by ultraviolet-inactivated virus. Herpes simplex virus type 2 (HSV-2) DNA has been detected by molecular hybridization in hamster fibroblast cells oncogenically transformed by ultraviolet-irradiated virus. At early passages after cloning in soft agar, about 40% of the HSV-2 genome was present in all the transformed cell lines at one to six copies per cell. In cell lines derived from tumors induced by these cells, the same percentage of the HSV-2 genome was also found with more uniform number of copies (between two and three). Thus the presence of viral DNA seems to be necessary for the maintenance of the transformed state in these cell lines."}
{"id": "PMID:224989", "title": "Studies of two temperature-sensitive mutants of Mengo virus.", "content": "Studies of the synthesis of viral ribonucleates and polypeptides in cells infected with two RNA- ts mutants of Mengo virus (ts 135 and ts 520) have shown that when ts 135 infected cells are shifted from the permissive (33 degrees C) to the nonpermissive (39 degrees C) temperature: (i) the synthesis of all three species of viral RNA (single stranded, replicative form, and replicative intermediate) is inhibited to about the same extent, and (ii) the posttranslational cleavage of structural polypeptide precursors A and B is partially blocked. Investigations of the in vivo and in vitro stability of the viral RNA replicase suggest that the RNA- phentotype reflects a temperature-sensitive defect in the enzyme. The second defect does not appear to result from the inhibition of viral RNA synthesis at 39 degrees C, since normal cleavage of polypeptides A and B occurs in wt Mengo-infected cells in which viral RNA synthesis is blocked by cordycepin, and at the nonpermissive temperature in ts 520 infected cells. Considered in toto, the evidence suggests that ts 135 is a double mutant. Subviral (53S) particles have been shown to accumulate in ts 520 (but not ts 135) infected cells when cultures are shifted from 33 to 39 degrees C. This observation provides supporting evidence for the proposal that this recently discovered particle is an intermediate in the assembly pathway of Mengo virions.", "contents": "Studies of two temperature-sensitive mutants of Mengo virus. Studies of the synthesis of viral ribonucleates and polypeptides in cells infected with two RNA- ts mutants of Mengo virus (ts 135 and ts 520) have shown that when ts 135 infected cells are shifted from the permissive (33 degrees C) to the nonpermissive (39 degrees C) temperature: (i) the synthesis of all three species of viral RNA (single stranded, replicative form, and replicative intermediate) is inhibited to about the same extent, and (ii) the posttranslational cleavage of structural polypeptide precursors A and B is partially blocked. Investigations of the in vivo and in vitro stability of the viral RNA replicase suggest that the RNA- phentotype reflects a temperature-sensitive defect in the enzyme. The second defect does not appear to result from the inhibition of viral RNA synthesis at 39 degrees C, since normal cleavage of polypeptides A and B occurs in wt Mengo-infected cells in which viral RNA synthesis is blocked by cordycepin, and at the nonpermissive temperature in ts 520 infected cells. Considered in toto, the evidence suggests that ts 135 is a double mutant. Subviral (53S) particles have been shown to accumulate in ts 520 (but not ts 135) infected cells when cultures are shifted from 33 to 39 degrees C. This observation provides supporting evidence for the proposal that this recently discovered particle is an intermediate in the assembly pathway of Mengo virions."}
{"id": "PMID:224990", "title": "Myoinositol biosynthesis by Sertoli cells, and levels of myoinositol biosynthetic enzymes in testis and epididymis.", "content": "Levels of glucose-6-phosphate cyclase (myoinsitol-1-phosphate synthase, EC 5.5.1.4) and myoinositol-1-phosphate phosphatase (myoinositol-1-phosphatase, EC 3.1.3.25) were determined in extracts of testes from10-, 20-, and 30-day-old rats, and in extracts of Sertoli cells, germinal cells, and epididymides. The specific activity of the cyclase was approximately 1/10th that of the phosphatase in all extracts found to contain either enzyme. Among cells in the testis examined, Sertoli cells had highest levels of enzymes required for inositol biosynthesis from glucose, while spermatocytes and round spermatids did not have detectable activity. Spermatozoa from the epididymis also had no detectable cyclase or phosphatase activity. In contrast, extracts of washed epididymides contained exceedingly high specific activities of these enzymes. Primary cultures of Sertoli cells, maintained in a chemically defined medium without added inositol, released inositol into the medium during three successive 24-h periods. The amounts released were greater in cells stimulated by dibutyryl cyclic AMP. Results were interpreted to indicate that inositol in the fluid of seminiferous tubules most probably originates from Sertoli cells, which synthesize inositol from glucose. Additional inositol in the fluid of epididymal tubules could readily be provided by metabolism of glucose by epididymal epithelial cells", "contents": "Myoinositol biosynthesis by Sertoli cells, and levels of myoinositol biosynthetic enzymes in testis and epididymis. Levels of glucose-6-phosphate cyclase (myoinsitol-1-phosphate synthase, EC 5.5.1.4) and myoinositol-1-phosphate phosphatase (myoinositol-1-phosphatase, EC 3.1.3.25) were determined in extracts of testes from10-, 20-, and 30-day-old rats, and in extracts of Sertoli cells, germinal cells, and epididymides. The specific activity of the cyclase was approximately 1/10th that of the phosphatase in all extracts found to contain either enzyme. Among cells in the testis examined, Sertoli cells had highest levels of enzymes required for inositol biosynthesis from glucose, while spermatocytes and round spermatids did not have detectable activity. Spermatozoa from the epididymis also had no detectable cyclase or phosphatase activity. In contrast, extracts of washed epididymides contained exceedingly high specific activities of these enzymes. Primary cultures of Sertoli cells, maintained in a chemically defined medium without added inositol, released inositol into the medium during three successive 24-h periods. The amounts released were greater in cells stimulated by dibutyryl cyclic AMP. Results were interpreted to indicate that inositol in the fluid of seminiferous tubules most probably originates from Sertoli cells, which synthesize inositol from glucose. Additional inositol in the fluid of epididymal tubules could readily be provided by metabolism of glucose by epididymal epithelial cells"}
{"id": "PMID:224991", "title": "Photooxidation of NADH by 2,3-butanedione: a potential source of error in studies on active site arginyl residues.", "content": "Incubation of NADH or NADPH with 2,3-butanedione in aqueous solution results in photooxidation of the reduced pyridine nucleotides under conditions of ordinary laboratory lighting. Maximum rates of photooxidation are obtained at pH 7 and with light at a wavelength of 410 nm. This reaction could lead to artifactual results in experiments on the role of arginyl groups in enzymes in which a reduced pyridine nucleotide is used to protect the active site residues from modification by 2,3-butanedione.", "contents": "Photooxidation of NADH by 2,3-butanedione: a potential source of error in studies on active site arginyl residues. Incubation of NADH or NADPH with 2,3-butanedione in aqueous solution results in photooxidation of the reduced pyridine nucleotides under conditions of ordinary laboratory lighting. Maximum rates of photooxidation are obtained at pH 7 and with light at a wavelength of 410 nm. This reaction could lead to artifactual results in experiments on the role of arginyl groups in enzymes in which a reduced pyridine nucleotide is used to protect the active site residues from modification by 2,3-butanedione."}
{"id": "PMID:224992", "title": "Restoration of virulence of axenically cultivated Entamoeba histolytica by cholesterol.", "content": "The lost pathogenicity of two strains of Entamoeba histolytica, one isolated in 1924 and the other in 1967, grown in axenic culture for the past 5 and 6 years respectively, was restored by supplementing the culture medium with cholesterol through a number of transfers. The number of passages in the cholesterol-supplemented medium, necessary to restore a certain degree of pathogenicity of the two strains in hamsters, was proportional to the total time of in vitro cultivation of the strain, and not just the time of cultivation under axenic conditions. Pathogenicity, once restored, persisted for a long time after cholesterol treatment was stopped.", "contents": "Restoration of virulence of axenically cultivated Entamoeba histolytica by cholesterol. The lost pathogenicity of two strains of Entamoeba histolytica, one isolated in 1924 and the other in 1967, grown in axenic culture for the past 5 and 6 years respectively, was restored by supplementing the culture medium with cholesterol through a number of transfers. The number of passages in the cholesterol-supplemented medium, necessary to restore a certain degree of pathogenicity of the two strains in hamsters, was proportional to the total time of in vitro cultivation of the strain, and not just the time of cultivation under axenic conditions. Pathogenicity, once restored, persisted for a long time after cholesterol treatment was stopped."}
{"id": "PMID:224993", "title": "Infection of inbred strains of mice with Sendai virus.", "content": "A comparative study of the consequences of Parainfluenza type 1 (Sendai) virus infection in inbred (C57B1/6J, C57Br, CBA, DBA) strains and a randomly bred (Swiss white) strain of mice showed significant mortality in the inbred strains but not in the randomly bred ones. This difference may be partly related to the high levels of virus growth obtained in the lungs of the inbred strains contrasted to little or no virus growth in the lungs of the Swiss white mice. A similar difference between these mice was found in the incidence of virus involvement of a variety of mouse tissues. These differences in mortality and in vivo growth of virus were not clearly mimicked in antiviral-antibody production in these different mouse populations.", "contents": "Infection of inbred strains of mice with Sendai virus. A comparative study of the consequences of Parainfluenza type 1 (Sendai) virus infection in inbred (C57B1/6J, C57Br, CBA, DBA) strains and a randomly bred (Swiss white) strain of mice showed significant mortality in the inbred strains but not in the randomly bred ones. This difference may be partly related to the high levels of virus growth obtained in the lungs of the inbred strains contrasted to little or no virus growth in the lungs of the Swiss white mice. A similar difference between these mice was found in the incidence of virus involvement of a variety of mouse tissues. These differences in mortality and in vivo growth of virus were not clearly mimicked in antiviral-antibody production in these different mouse populations."}
{"id": "PMID:224994", "title": "Second-step concentration of viruses in drinking and surface waters using polyethylene glycol hydroextraction.", "content": "In our laboratory, virus adsorbed to talc--Celite layers is eluted with 100 mL of 10% fetal calf serum (FCS) in normal saline (pH 9.0). A further 10-fold reduction in the volume of the eluate was necessary before its inoculation into cell cultures. A 100-mL volume of an experimentally contaminated sample was placed in a dialysis sac and hydroextracted overnight (4 degrees C) with polyethylene glycol (PEG) 6000. The viscous material remaining in the sac was resuspended in 10 mL of Earle's balanced salt solution. After membrane filtration (0.2 micron), the concentrate was plaque assayed in BS-C-1 cells. Using this technique, recoveries of five laboratory-adapted enteric viruses (polio 1, echo 6, coxsackie B5, coxackie A9, and reo 3) and four freshly isolated enteric virus strains (polio 1, echo 1, coxsackie B3, and reo) ranged from 87 to 97%. In comparative tests, PEG hydroextraction was simpler and superior to organic flocculation.", "contents": "Second-step concentration of viruses in drinking and surface waters using polyethylene glycol hydroextraction. In our laboratory, virus adsorbed to talc--Celite layers is eluted with 100 mL of 10% fetal calf serum (FCS) in normal saline (pH 9.0). A further 10-fold reduction in the volume of the eluate was necessary before its inoculation into cell cultures. A 100-mL volume of an experimentally contaminated sample was placed in a dialysis sac and hydroextracted overnight (4 degrees C) with polyethylene glycol (PEG) 6000. The viscous material remaining in the sac was resuspended in 10 mL of Earle's balanced salt solution. After membrane filtration (0.2 micron), the concentrate was plaque assayed in BS-C-1 cells. Using this technique, recoveries of five laboratory-adapted enteric viruses (polio 1, echo 6, coxsackie B5, coxackie A9, and reo 3) and four freshly isolated enteric virus strains (polio 1, echo 1, coxsackie B3, and reo) ranged from 87 to 97%. In comparative tests, PEG hydroextraction was simpler and superior to organic flocculation."}
{"id": "PMID:224995", "title": "[Induction and repression of the collagenase synthesis in Acinetobacter sp].", "content": "The synthesis of collagenase in Acinetobacter sp. was found to be inducible by denatured collagen and by its high molecular weight fragments. The presence in the inducer of part of the tertiary structure appear to be indispensable. On the other hand, an addition of Casamino acids, meat protein hydrolysate, or a mixture of amino acids with a similar composition to gelatin does not stimulate collagenase synthesis. Enzyme production was severely repressed in the early phase of growth by glucose, arabinose, and ribose, single amino acids, proline, hydroxyproline, alanine, glutamic acid or casein acid hydrolysate. A mechanism of repression similar to catabolite repression was involved in the phenomenon caused by carbohydrates. However, the fact that cyclic adenosine 3'5-monophosphate did not overcome the repression caused by amino acids or Casamino acids, in contrast to classical catabolite repression, suggests that these two forms of repression may be distinct.", "contents": "[Induction and repression of the collagenase synthesis in Acinetobacter sp]. The synthesis of collagenase in Acinetobacter sp. was found to be inducible by denatured collagen and by its high molecular weight fragments. The presence in the inducer of part of the tertiary structure appear to be indispensable. On the other hand, an addition of Casamino acids, meat protein hydrolysate, or a mixture of amino acids with a similar composition to gelatin does not stimulate collagenase synthesis. Enzyme production was severely repressed in the early phase of growth by glucose, arabinose, and ribose, single amino acids, proline, hydroxyproline, alanine, glutamic acid or casein acid hydrolysate. A mechanism of repression similar to catabolite repression was involved in the phenomenon caused by carbohydrates. However, the fact that cyclic adenosine 3'5-monophosphate did not overcome the repression caused by amino acids or Casamino acids, in contrast to classical catabolite repression, suggests that these two forms of repression may be distinct."}
{"id": "PMID:224996", "title": "High yields of coatless spores of Clostridium perfringens strain 8--6 in a defined medium.", "content": "Coatless spores of mutant strain 8--6 of Clostridium perfringens were formed reproducibly at levels exceeding 10(7)/mL in a defined medium. Confirming previous observations, the spores are quite stable in water and resistant to heat, octanol, and ethanol. They also resist 5% phenol. Electron microscopy confirms, with further evidence, the probable absence of any structure exterior to the cortex. The levels of sporulation attained are sufficient to permit recovery and purification for future studies on physicochemical and germination properties. The defined medium makes possible studies on spore coat (and exterotoxin) biosynthesis and coat assembly.", "contents": "High yields of coatless spores of Clostridium perfringens strain 8--6 in a defined medium. Coatless spores of mutant strain 8--6 of Clostridium perfringens were formed reproducibly at levels exceeding 10(7)/mL in a defined medium. Confirming previous observations, the spores are quite stable in water and resistant to heat, octanol, and ethanol. They also resist 5% phenol. Electron microscopy confirms, with further evidence, the probable absence of any structure exterior to the cortex. The levels of sporulation attained are sufficient to permit recovery and purification for future studies on physicochemical and germination properties. The defined medium makes possible studies on spore coat (and exterotoxin) biosynthesis and coat assembly."}
{"id": "PMID:224997", "title": "The superiority of combination chemotherapy over single agent chemotherapy in small cell lung carcinoma.", "content": "From June 1974 to October 1976, 288 patients with small cell undifferentiated lung carcinoma were entered into a randomized, controlled study comparing the two noncycle-active induction regimens of cyclophosphamide vs. the combination of cyclophosphamide, doxorubicin and imidazole carboximide (DTIC). Patients were stratified by extent of disease, previous radiotherapy and performance status. Responding patients and those who did not progress were then randomized to receive their initial regimen alone, or their initial regimen with added cycle-active therapy (vincristine, hydroxyurea and methotrexate). While only 4/34 (12%) evaluable patients treated with cyclophosphamide achieved a response (greater than 50% regression), a final total of 119/217 (57%) evaluable patients on the three drugs have responded (p = 0.005). The survival curve for all the combination-treated patients was significantly better than for those treated with cyclophosphamide alone (p = 0.012). There was no demonstrable statistical superiority in length of remission or survival for patients on the combination who received in addition cycle-active consolidation therapy. In the combination chemotherapy group, survival duration was longer for patients with limited disease than extensive disease (p = 0.035). There was a strong correlation between quality of remission produced by the combination and survival.", "contents": "The superiority of combination chemotherapy over single agent chemotherapy in small cell lung carcinoma. From June 1974 to October 1976, 288 patients with small cell undifferentiated lung carcinoma were entered into a randomized, controlled study comparing the two noncycle-active induction regimens of cyclophosphamide vs. the combination of cyclophosphamide, doxorubicin and imidazole carboximide (DTIC). Patients were stratified by extent of disease, previous radiotherapy and performance status. Responding patients and those who did not progress were then randomized to receive their initial regimen alone, or their initial regimen with added cycle-active therapy (vincristine, hydroxyurea and methotrexate). While only 4/34 (12%) evaluable patients treated with cyclophosphamide achieved a response (greater than 50% regression), a final total of 119/217 (57%) evaluable patients on the three drugs have responded (p = 0.005). The survival curve for all the combination-treated patients was significantly better than for those treated with cyclophosphamide alone (p = 0.012). There was no demonstrable statistical superiority in length of remission or survival for patients on the combination who received in addition cycle-active consolidation therapy. In the combination chemotherapy group, survival duration was longer for patients with limited disease than extensive disease (p = 0.035). There was a strong correlation between quality of remission produced by the combination and survival."}
{"id": "PMID:224998", "title": "Radical radiation therapy of advanced lung cancer: evaluation of prognostic factors and results of continuous and split course treatment.", "content": "One hundred patients with inoperable (80) or unresectable (20) bronchogenic carcinoma without evidence of spread beyond the thorax and supraclavicular nodes were planned for radical radiotherapy. Seventy-six patients received continuous irradiation (6000 rads in 30 treatments in 6 weeks, TDF 99) and 24 received split course therapy (2 courses of 2500 rads in 10 treatments with a 3 week break between courses, TDF 88). Forty-three patients had squamous cell carcinoma or adenocarcinoma and were considered to have favorable prognostic factors, while 57 patients had unfavorable prognostic factors: undifferentiated large cell or small cell carcinoma, supraclavicular metastases, SVC obstruction, superior sulcus tumors, or bone erosion in continuity with the tumor. Ninety-two patients completed the planned course of treatment. In patients completing treatment, local control of cancer within the irradiated volume was achieved in 58.5% of continuously irradiated patients and 45.4% of patients receiving split course therapy. Median survival was 1.2 months in patients not completing treatment and 12 months for the patients who completed treatment; 19% of the total group survived 3 years. Median and 3 year survivals of 14 months and 20.4% and of 9 months and 11% were observed for patients treated continuously and by the split course techniques, respectively. Corresponding survival figures for patients with favorable and unfavorable prognostic signs were 21 months and 26%, and 4 months and 11%, respectively. Implications of these data for treatment planning and patient selection for radical radiotherapy in bronchogenic carcinoma are discussed.", "contents": "Radical radiation therapy of advanced lung cancer: evaluation of prognostic factors and results of continuous and split course treatment. One hundred patients with inoperable (80) or unresectable (20) bronchogenic carcinoma without evidence of spread beyond the thorax and supraclavicular nodes were planned for radical radiotherapy. Seventy-six patients received continuous irradiation (6000 rads in 30 treatments in 6 weeks, TDF 99) and 24 received split course therapy (2 courses of 2500 rads in 10 treatments with a 3 week break between courses, TDF 88). Forty-three patients had squamous cell carcinoma or adenocarcinoma and were considered to have favorable prognostic factors, while 57 patients had unfavorable prognostic factors: undifferentiated large cell or small cell carcinoma, supraclavicular metastases, SVC obstruction, superior sulcus tumors, or bone erosion in continuity with the tumor. Ninety-two patients completed the planned course of treatment. In patients completing treatment, local control of cancer within the irradiated volume was achieved in 58.5% of continuously irradiated patients and 45.4% of patients receiving split course therapy. Median survival was 1.2 months in patients not completing treatment and 12 months for the patients who completed treatment; 19% of the total group survived 3 years. Median and 3 year survivals of 14 months and 20.4% and of 9 months and 11% were observed for patients treated continuously and by the split course techniques, respectively. Corresponding survival figures for patients with favorable and unfavorable prognostic signs were 21 months and 26%, and 4 months and 11%, respectively. Implications of these data for treatment planning and patient selection for radical radiotherapy in bronchogenic carcinoma are discussed."}
{"id": "PMID:224999", "title": "Delayed radiation necrosis of brainstem related to fast neutron beam irradiation: case report and literature review.", "content": "A 42-year-old man developed necrosis of the brainstem 10 months following fast neutron irradiation of a recurrent adenocystic carcinoma of the right submandibular salivary gland. The neoplasm had been diagnosed 15 years earlier. Neck dissection and several local excisions failed to control local extension, so that 7000 rad 4.8 MeV x-rays were administered. The right mandible and part of the tongue and palate were resected for recurrence and chemotherapy and transfer factor were given. Because of cranial neuropathy and erosion of the skull base, fast neutron radiation (2.080 rads) was administered five and one-half years after the x-ray therapy, but to a nonoverlapping field. Ten months later, rapidly progressive symptoms and signs of multiple cranial nerve palsies on the right side and left hemihypesthesia and hemiplegia appeared. Clinical manifestations of brainstem necrosis lasted 4 months. Postmortem examination demonstrated radionecrosis of pons and upper medulla, predominantly on the right side. This case illustrates the efficacy of neutron radiation in eradicating local carcinoma and also the serious complications of this therapeutic modality.", "contents": "Delayed radiation necrosis of brainstem related to fast neutron beam irradiation: case report and literature review. A 42-year-old man developed necrosis of the brainstem 10 months following fast neutron irradiation of a recurrent adenocystic carcinoma of the right submandibular salivary gland. The neoplasm had been diagnosed 15 years earlier. Neck dissection and several local excisions failed to control local extension, so that 7000 rad 4.8 MeV x-rays were administered. The right mandible and part of the tongue and palate were resected for recurrence and chemotherapy and transfer factor were given. Because of cranial neuropathy and erosion of the skull base, fast neutron radiation (2.080 rads) was administered five and one-half years after the x-ray therapy, but to a nonoverlapping field. Ten months later, rapidly progressive symptoms and signs of multiple cranial nerve palsies on the right side and left hemihypesthesia and hemiplegia appeared. Clinical manifestations of brainstem necrosis lasted 4 months. Postmortem examination demonstrated radionecrosis of pons and upper medulla, predominantly on the right side. This case illustrates the efficacy of neutron radiation in eradicating local carcinoma and also the serious complications of this therapeutic modality."}
{"id": "PMID:225000", "title": "Elevated prolactin levels in bronchogenic carcinoma.", "content": "The frequency and significance of hyperprolactinemia was studied in 21 consecutive, untreated male patients with bronchogenic carcinoma. Seven patients (33%) were found to have elevated serum prolactin (hPRL) levels. No correlation was demonstrated between increased hPRL levels, tissue histology, or tumor burden. L-dopa suppression and/or TRH stimulation tests were obtained in three untreated patients with hyperprolactinemia. The results of these tests were considered normal suggesting hypothalamic control.", "contents": "Elevated prolactin levels in bronchogenic carcinoma. The frequency and significance of hyperprolactinemia was studied in 21 consecutive, untreated male patients with bronchogenic carcinoma. Seven patients (33%) were found to have elevated serum prolactin (hPRL) levels. No correlation was demonstrated between increased hPRL levels, tissue histology, or tumor burden. L-dopa suppression and/or TRH stimulation tests were obtained in three untreated patients with hyperprolactinemia. The results of these tests were considered normal suggesting hypothalamic control."}
{"id": "PMID:225001", "title": "The value of carcinoembryonic antigen in patients with carcinoma of the lung.", "content": "Carcinoembryonic antigen levels in 682 lung cancer patients have been studied in order to assess their value in the screening of high-risk populations, monitoring total surgical ablation and projecting the effectiveness of therapy. The initial values are shown to be related to the histology of the tumor and to the extent of the disease. All histologic types of lung cancer produce elevated CEA but adenocarcinoma characteristically produces higher values than small, large or squamous cell carcinomas. CEA has its most precise value in distinguishing at an early date cured patients subsequent to surgical resection from those patients who will eventually fail because of recurrent disease.", "contents": "The value of carcinoembryonic antigen in patients with carcinoma of the lung. Carcinoembryonic antigen levels in 682 lung cancer patients have been studied in order to assess their value in the screening of high-risk populations, monitoring total surgical ablation and projecting the effectiveness of therapy. The initial values are shown to be related to the histology of the tumor and to the extent of the disease. All histologic types of lung cancer produce elevated CEA but adenocarcinoma characteristically produces higher values than small, large or squamous cell carcinomas. CEA has its most precise value in distinguishing at an early date cured patients subsequent to surgical resection from those patients who will eventually fail because of recurrent disease."}
{"id": "PMID:225002", "title": "Histopathology of nasopharyngeal carcinoma: correlations with epidemiology, survival rates and other biological characteristics.", "content": "A total of 363 cases of nasopharyngeal carcinoma (NPC) in Singapore were classified into squamous cell carcinoma (SCC; 73 cases), non-keratinizing carcinoma (NKC; 178 cases) and undifferentiated carcinoma (UC; 172 cases). Possible biological differences between these histologic types and between tumors with and without lymphocytic infiltration were investigated by correlations with survival rates and with selected epidemiologic, immunovirologic, and immunogenetic data on the disease. The 5-year survival rates following radiotherapy were 25.3% for all cases and 58.8% for tumors restricted to the nasopharynx. The 5-year survival rate for SCC was poorer than for the combined NKC and UC groups (p less than 0.05). The 3-year survival rate was better for tumors with lymphocytic infiltration (p less than 0.05), but there were no differences in the 5-year survivals. The survival rates were better in females (p less than 0.01) and in the younger age groups (p less than 0.01). There were no significant correlations between histopathology of NPC and the distributions of cases by age, sex, HLA antigen profiles, or cell-mediated immune status. Squamous cell carcinoma was associated with lower levels of antibodies to the Epstein-Barr nuclear antigen (p less than 0.05), but there were no differences with respect to antibodies against other EBV related antigens. These findings support the view that SCC, NKC, and UC of the nasopharynx, as defined in the WHO classification, are variants of a fairly homogeneous group of neoplasms in the Singapore population.", "contents": "Histopathology of nasopharyngeal carcinoma: correlations with epidemiology, survival rates and other biological characteristics. A total of 363 cases of nasopharyngeal carcinoma (NPC) in Singapore were classified into squamous cell carcinoma (SCC; 73 cases), non-keratinizing carcinoma (NKC; 178 cases) and undifferentiated carcinoma (UC; 172 cases). Possible biological differences between these histologic types and between tumors with and without lymphocytic infiltration were investigated by correlations with survival rates and with selected epidemiologic, immunovirologic, and immunogenetic data on the disease. The 5-year survival rates following radiotherapy were 25.3% for all cases and 58.8% for tumors restricted to the nasopharynx. The 5-year survival rate for SCC was poorer than for the combined NKC and UC groups (p less than 0.05). The 3-year survival rate was better for tumors with lymphocytic infiltration (p less than 0.05), but there were no differences in the 5-year survivals. The survival rates were better in females (p less than 0.01) and in the younger age groups (p less than 0.01). There were no significant correlations between histopathology of NPC and the distributions of cases by age, sex, HLA antigen profiles, or cell-mediated immune status. Squamous cell carcinoma was associated with lower levels of antibodies to the Epstein-Barr nuclear antigen (p less than 0.05), but there were no differences with respect to antibodies against other EBV related antigens. These findings support the view that SCC, NKC, and UC of the nasopharynx, as defined in the WHO classification, are variants of a fairly homogeneous group of neoplasms in the Singapore population."}
{"id": "PMID:225003", "title": "Relationship between survival and histologic type in small cell anaplastic carcinoma of the lung.", "content": "Survival and histologic subtype were compared in 61 patients with small cell anaplastic lung cancer. Patients with lymphocyte-like (oat cell) and fusiform histologies treated with chemotherapy had longer median survivals than the polygonal and other varieties on the same treatment. Likewise, when detectable disease was confined to the chest and supraclavicular nodes, the patients with lymphocyte-like and fusiform types lived longer. The improved survival in the lymphocyte-like and fusiform categories accounted for most of our improved overall median survival rates with the COPP regimen in small cell lung cancer. Survival in the polygonal and other types was not appreciably different from that seen in non-small cell lung cancer (squamous and adenocarcinoma). It may be possible to refine treatment plans on the basis of cell type so as to further increase survival in small cell anaplastic lung carcinoma.", "contents": "Relationship between survival and histologic type in small cell anaplastic carcinoma of the lung. Survival and histologic subtype were compared in 61 patients with small cell anaplastic lung cancer. Patients with lymphocyte-like (oat cell) and fusiform histologies treated with chemotherapy had longer median survivals than the polygonal and other varieties on the same treatment. Likewise, when detectable disease was confined to the chest and supraclavicular nodes, the patients with lymphocyte-like and fusiform types lived longer. The improved survival in the lymphocyte-like and fusiform categories accounted for most of our improved overall median survival rates with the COPP regimen in small cell lung cancer. Survival in the polygonal and other types was not appreciably different from that seen in non-small cell lung cancer (squamous and adenocarcinoma). It may be possible to refine treatment plans on the basis of cell type so as to further increase survival in small cell anaplastic lung carcinoma."}
{"id": "PMID:225004", "title": "Chemotherapy of nonirradiated malignant gliomas. Phase II: study of the combination of methyl-CCNU, vincristine, and procarbazine.", "content": "Twenty-eight adult patients with nonirradiated malignant gliomas of the brain were administered a combination of methyl-CCNU (130 mg/m2, p.o., day 1), vincristine (2 mg/m2, i.v., day 1) and procarbazine (100 mg/m2, p.o., days 2 to 15) (MVP), scheduled to be given at successive 6 week intervals. Nineteen (67.9%) were not responsive to MVP and 9 (32.1%) were. Of 16 who had previous partial resection of their tumors, 8 (50%) responded to MVP and 8 (50%) did not. Of 12 who had previous biopsy, only 1 (8.3%) responded. Overall 1-year survival rate for the 28 patients was 28.6%. Major side effects of MVP were leukopenia, thrombocytopenia, pulmonary emboli, and thrombophlebitis, detected mainly during the first 20 to 24 weeks of treatment.", "contents": "Chemotherapy of nonirradiated malignant gliomas. Phase II: study of the combination of methyl-CCNU, vincristine, and procarbazine. Twenty-eight adult patients with nonirradiated malignant gliomas of the brain were administered a combination of methyl-CCNU (130 mg/m2, p.o., day 1), vincristine (2 mg/m2, i.v., day 1) and procarbazine (100 mg/m2, p.o., days 2 to 15) (MVP), scheduled to be given at successive 6 week intervals. Nineteen (67.9%) were not responsive to MVP and 9 (32.1%) were. Of 16 who had previous partial resection of their tumors, 8 (50%) responded to MVP and 8 (50%) did not. Of 12 who had previous biopsy, only 1 (8.3%) responded. Overall 1-year survival rate for the 28 patients was 28.6%. Major side effects of MVP were leukopenia, thrombocytopenia, pulmonary emboli, and thrombophlebitis, detected mainly during the first 20 to 24 weeks of treatment."}
{"id": "PMID:225005", "title": "Absence of carcinoembryonic antigen-like material in mesothelioma: an immunohistochemical differentiation from other lung cancers.", "content": "This study is to examine the potential usefulness of immunohistochemical staining for carcinoembryonic antigen (CEA)-like material in the differential diagnosis of mesotheliomas (12 cases) from other lung cancers (14 cases) that had been previously diagnosed by transmission and scanning electron microscopy and conventional light microscopy. Indirect immunofluorescent staining for CEA was carried out on formalin-fixed paraffin-embedded sections, and the slides were examined under code. All 9 cases of diffuse mesothelioma were negative, and all 12 cases of adenocarcinoma and bronchioloalveolar carcinoma were positive for CEA-like material. Three localized mesotheliomas and a carcinoid tumor were also negative. A squamous cell carcinoma was positive. A positive immunohistochemical result for CEA-like material in lung cancers will raise the possibility of its being of bronchial epithelial origin.", "contents": "Absence of carcinoembryonic antigen-like material in mesothelioma: an immunohistochemical differentiation from other lung cancers. This study is to examine the potential usefulness of immunohistochemical staining for carcinoembryonic antigen (CEA)-like material in the differential diagnosis of mesotheliomas (12 cases) from other lung cancers (14 cases) that had been previously diagnosed by transmission and scanning electron microscopy and conventional light microscopy. Indirect immunofluorescent staining for CEA was carried out on formalin-fixed paraffin-embedded sections, and the slides were examined under code. All 9 cases of diffuse mesothelioma were negative, and all 12 cases of adenocarcinoma and bronchioloalveolar carcinoma were positive for CEA-like material. Three localized mesotheliomas and a carcinoid tumor were also negative. A squamous cell carcinoma was positive. A positive immunohistochemical result for CEA-like material in lung cancers will raise the possibility of its being of bronchial epithelial origin."}
{"id": "PMID:225006", "title": "Sclerosing hemangioma of the lung: an ultrastructural study.", "content": "A well-circumscribed nodular mass was excised from the lingula of the left lung of a 40-year-old-female. The lesion was discovered on routine chest x-ray examination and corresponded to a typical \"sclerosing hemangioma\" described by Liebow and Hubbell. Electron microscopic study revealed unequivocal epithelial cells in both the irregular spaces and the solid areas of the tumor; some of these cells were identical to granular pneumonocytes. The true vascular component was sparsely distributed. We concluded that \"sclerosing hemangioma\" was a misnomer because we were dealing with an essentially epithelial lesion.", "contents": "Sclerosing hemangioma of the lung: an ultrastructural study. A well-circumscribed nodular mass was excised from the lingula of the left lung of a 40-year-old-female. The lesion was discovered on routine chest x-ray examination and corresponded to a typical \"sclerosing hemangioma\" described by Liebow and Hubbell. Electron microscopic study revealed unequivocal epithelial cells in both the irregular spaces and the solid areas of the tumor; some of these cells were identical to granular pneumonocytes. The true vascular component was sparsely distributed. We concluded that \"sclerosing hemangioma\" was a misnomer because we were dealing with an essentially epithelial lesion."}
{"id": "PMID:225007", "title": "Cell kinetic analyses of human malignant brain tumors (gliomas).", "content": "Administration of 3H-thymidine, either with or without mitostatic agents, to 24 patients with various gliomas revealed 1) in viable areas a labeling index (LI) for glioblastomas equal to 5-15%, 2) an LI of 1% or less in well-differentiated gliomas, and 3) the LI of anaplastic astrocytomas was intermediate and reflected the extent of anaplasia. Growth fraction was 0.14-0.44 in malignant gliomas (average 0.31 +/- 0.10), and cell cycle time obtained by means of stathmokinetic analysis was 75.6 +/- 45.7 hr. With few exceptions, the patients whose tumors showed an LI of 5% or more died within 1 year after the onset of disease, and no patients whose tumors at biopsy had an LI of over 5% survived more than 6 months. In contrast, there was a far better prognosis for patients whose tumors demonstrated an LI of less than 1%.", "contents": "Cell kinetic analyses of human malignant brain tumors (gliomas). Administration of 3H-thymidine, either with or without mitostatic agents, to 24 patients with various gliomas revealed 1) in viable areas a labeling index (LI) for glioblastomas equal to 5-15%, 2) an LI of 1% or less in well-differentiated gliomas, and 3) the LI of anaplastic astrocytomas was intermediate and reflected the extent of anaplasia. Growth fraction was 0.14-0.44 in malignant gliomas (average 0.31 +/- 0.10), and cell cycle time obtained by means of stathmokinetic analysis was 75.6 +/- 45.7 hr. With few exceptions, the patients whose tumors showed an LI of 5% or more died within 1 year after the onset of disease, and no patients whose tumors at biopsy had an LI of over 5% survived more than 6 months. In contrast, there was a far better prognosis for patients whose tumors demonstrated an LI of less than 1%."}
{"id": "PMID:225008", "title": "Virus-associated hemophagocytic syndrome: a benign histiocytic proliferation distinct from malignant histiocytosis.", "content": "Nineteen patients whose bone marrow smears showed histiocytic hyperplasia with prominent hemophagocytosis were found to have a clinicopathologic syndrome associated with active viral infection. High fever, constitutional symptoms, liver function, and coagulation abnormalities and peripheral blood cytopenias were characteristic findings. Hepatosplenomegaly, lymphadenopathy, bilateral pulmonary infiltrates, and skin rash were often present. Fourteen of the patients were immunosuppressed. Active infection by herpes group viruses was documented in 14 patients and by adenovirus in 1. The bone marrow of most patients also showed decreased granulopoiesis and erythropoiesis with normal to increased numbers of megakaryocytes. Treatment generally consisted of supportive therapy and withdrawal of immunosuppressive drugs. Thirteen patients recovered. Lymph node biopsy and autopsy material showed generalized histiocytic hyperplasia with hemophagocytosis. The relationship of this disorder to familial hemophagocytic reticulosis, familial erythrophagocytic lymphohistiocytosis, histiocytic medullary reticulosis, and malignant histiocytosis is discussed. Immunosuppressive and cytotoxic therapy may be contraindicated in the treatment of this virus-associated syndrome.", "contents": "Virus-associated hemophagocytic syndrome: a benign histiocytic proliferation distinct from malignant histiocytosis. Nineteen patients whose bone marrow smears showed histiocytic hyperplasia with prominent hemophagocytosis were found to have a clinicopathologic syndrome associated with active viral infection. High fever, constitutional symptoms, liver function, and coagulation abnormalities and peripheral blood cytopenias were characteristic findings. Hepatosplenomegaly, lymphadenopathy, bilateral pulmonary infiltrates, and skin rash were often present. Fourteen of the patients were immunosuppressed. Active infection by herpes group viruses was documented in 14 patients and by adenovirus in 1. The bone marrow of most patients also showed decreased granulopoiesis and erythropoiesis with normal to increased numbers of megakaryocytes. Treatment generally consisted of supportive therapy and withdrawal of immunosuppressive drugs. Thirteen patients recovered. Lymph node biopsy and autopsy material showed generalized histiocytic hyperplasia with hemophagocytosis. The relationship of this disorder to familial hemophagocytic reticulosis, familial erythrophagocytic lymphohistiocytosis, histiocytic medullary reticulosis, and malignant histiocytosis is discussed. Immunosuppressive and cytotoxic therapy may be contraindicated in the treatment of this virus-associated syndrome."}
{"id": "PMID:225009", "title": "Carcinogenic effect of N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine, a postulated proximate pancreatic carcinogen in Syrian hamsters.", "content": "N-Nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) proved to be a potent carcinogen in Syrian golden hamsters. The compound is an in vivo metabolite of N-nitrosobis(2-hydroxypropyl)amine, N-nitrosobis(2-oxopropyl)amine (BOP), and N-nitroso-2,6-dimethylmorpholine and a postulated proximate pancreatic carcinogen in hamsters. As with BOP, HPOP induced a higher incidence of pancreatic ductular adenocarcinomas than did N-nitrosobis(2-hydroxypropyl)amine and N-nitroso-2,6-dimethylmorpholine, and these neoplasms showed a great tendency for invasion and metastasis. Also, HPOP induced tumors of the forestomach, liver, gallbladder, kidneys, and vagina (as did BOP). However, HPOP [unlike BOP, but like N-nitrosobis(2-hydroxypropyl)amine and N-nitroso-2,6-dimethylmorpholine] led to tumor development in the nasal cavity, larynx, trachea, intestine, Harderian gland, lips, and flank organ. The possible mechanisms of HPOP carcinogenicity are discussed.", "contents": "Carcinogenic effect of N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine, a postulated proximate pancreatic carcinogen in Syrian hamsters. N-Nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) proved to be a potent carcinogen in Syrian golden hamsters. The compound is an in vivo metabolite of N-nitrosobis(2-hydroxypropyl)amine, N-nitrosobis(2-oxopropyl)amine (BOP), and N-nitroso-2,6-dimethylmorpholine and a postulated proximate pancreatic carcinogen in hamsters. As with BOP, HPOP induced a higher incidence of pancreatic ductular adenocarcinomas than did N-nitrosobis(2-hydroxypropyl)amine and N-nitroso-2,6-dimethylmorpholine, and these neoplasms showed a great tendency for invasion and metastasis. Also, HPOP induced tumors of the forestomach, liver, gallbladder, kidneys, and vagina (as did BOP). However, HPOP [unlike BOP, but like N-nitrosobis(2-hydroxypropyl)amine and N-nitroso-2,6-dimethylmorpholine] led to tumor development in the nasal cavity, larynx, trachea, intestine, Harderian gland, lips, and flank organ. The possible mechanisms of HPOP carcinogenicity are discussed."}
{"id": "PMID:225010", "title": "Comparison of virus-positive and virus-negative cases of feline leukemia and lymphoma.", "content": "One hundred eighty-four cases of feline leukemia and lymphoma diagnosed in Boston from 1972 through 1976 were investigated. Fifty-eight % of these cases were lymphoma, and 42% were leukemia. Sixty-seven % of the cats had positive fluorescent antibody tests for circulating feline leukemia virus. The rest (33%) were virus negative. Clinically and epidemiologically, the virus-positive and virus-negative cases were remarkably similar except for their age at diagnosis. Virus-negative cats tended to be older (mean age at diagnosis, 4.9 years) as compared to virus-positive cats (3.5 years). For 22 cases of leukemia and lymphoma diagnosed after the age of 8 years, 15 were virus negative. The minimum mean induction period (time from first positive virus test to diagnosis of cancer) for 19 cats that were virus positive and healthy at their first test was 16.7 months (range, 2 to 41 months).", "contents": "Comparison of virus-positive and virus-negative cases of feline leukemia and lymphoma. One hundred eighty-four cases of feline leukemia and lymphoma diagnosed in Boston from 1972 through 1976 were investigated. Fifty-eight % of these cases were lymphoma, and 42% were leukemia. Sixty-seven % of the cats had positive fluorescent antibody tests for circulating feline leukemia virus. The rest (33%) were virus negative. Clinically and epidemiologically, the virus-positive and virus-negative cases were remarkably similar except for their age at diagnosis. Virus-negative cats tended to be older (mean age at diagnosis, 4.9 years) as compared to virus-positive cats (3.5 years). For 22 cases of leukemia and lymphoma diagnosed after the age of 8 years, 15 were virus negative. The minimum mean induction period (time from first positive virus test to diagnosis of cancer) for 19 cats that were virus positive and healthy at their first test was 16.7 months (range, 2 to 41 months)."}
{"id": "PMID:225011", "title": "Content of gonadotropins in cultured human malignant cells and effects of sodium butyrate treatment on gonadotropin secretion by HeLa cells.", "content": "Twenty-one of 82 human cell lines examined for production of human chorionic gonadotropin and its subunits (HCG-alpha and HCG-beta) produced either one or both subunits at some phase in their growth. Of these, 14 produced an excess amount of free alpha subunit, and seven produced HCG-beta or complete HCG without evidence for free alpha subunit synthesis. Five of the HCG-producing cell lines also contained or secreted the beta subunit of human luteinizing hormone. CBT cells derived from a glioblastoma multiforme and JAR choriocarcinoma cells secreted significant amounts of the beta subunit of human luteinizing hormone, while three other cell lines (breast carcinoma MCF-7, HeLa S3, and melanoma A375) produced small amounts of the beta subunit of human luteinizing hormone but did not appear to secrete it. Two cell lines (the melanoma line A375 and the SV40-transformed line SV80) appeared to contain small amounts of human follicle-stimulating hormone. Sodium butyrate caused a 40-fold induction in the secretion of both HCG-alpha and HCG-beta by HeLa S3 cells, but the total amount of HCG-alpha secretion induced was 800-fold greater than that of HCG-beta. Induction was blocked by actinomycin D (1 microgram/ml) and cycloheximide (5 microgram/ml) but was not affected by 1-beta-D-arabinofuranosylcytosine at a concentration (5 microgram/ml) that blocked DNA synthesis 99%. These results indicate that a number of malignant human cell lines produce the subunits of both placental and pituitary gonadotropins and that there is frequently an excess secretion of the free alpha subunit common to these hormones.", "contents": "Content of gonadotropins in cultured human malignant cells and effects of sodium butyrate treatment on gonadotropin secretion by HeLa cells. Twenty-one of 82 human cell lines examined for production of human chorionic gonadotropin and its subunits (HCG-alpha and HCG-beta) produced either one or both subunits at some phase in their growth. Of these, 14 produced an excess amount of free alpha subunit, and seven produced HCG-beta or complete HCG without evidence for free alpha subunit synthesis. Five of the HCG-producing cell lines also contained or secreted the beta subunit of human luteinizing hormone. CBT cells derived from a glioblastoma multiforme and JAR choriocarcinoma cells secreted significant amounts of the beta subunit of human luteinizing hormone, while three other cell lines (breast carcinoma MCF-7, HeLa S3, and melanoma A375) produced small amounts of the beta subunit of human luteinizing hormone but did not appear to secrete it. Two cell lines (the melanoma line A375 and the SV40-transformed line SV80) appeared to contain small amounts of human follicle-stimulating hormone. Sodium butyrate caused a 40-fold induction in the secretion of both HCG-alpha and HCG-beta by HeLa S3 cells, but the total amount of HCG-alpha secretion induced was 800-fold greater than that of HCG-beta. Induction was blocked by actinomycin D (1 microgram/ml) and cycloheximide (5 microgram/ml) but was not affected by 1-beta-D-arabinofuranosylcytosine at a concentration (5 microgram/ml) that blocked DNA synthesis 99%. These results indicate that a number of malignant human cell lines produce the subunits of both placental and pituitary gonadotropins and that there is frequently an excess secretion of the free alpha subunit common to these hormones."}
{"id": "PMID:225012", "title": "An infectivity assay for bovine leukemia virus using the immunoperoxidase technique.", "content": "This report describes the development of a 7-day infectivity assay for bovine leukemia virus (BLV) which is based on the induction of the major internal virion antigen (a protein with a molecular weight of 25,000) in susceptible indicator monolayer cell cultures. In this assay, the antigen is detected in the indicator cells by the immunoperoxidase antibody technique using a specific rabbit antiserum to a BLV protein with a molecular weight of 25,000. The immunoperoxidase infectivity assay is specific, quantitative, reproducible, and more sensitive than the previously described syncytia induction assay. The immunoperoxidase infectivity assay can be applied to the detection of BLV-infected cells and provides a reliable method for the direct diagnosis of BLV infection in cattle.", "contents": "An infectivity assay for bovine leukemia virus using the immunoperoxidase technique. This report describes the development of a 7-day infectivity assay for bovine leukemia virus (BLV) which is based on the induction of the major internal virion antigen (a protein with a molecular weight of 25,000) in susceptible indicator monolayer cell cultures. In this assay, the antigen is detected in the indicator cells by the immunoperoxidase antibody technique using a specific rabbit antiserum to a BLV protein with a molecular weight of 25,000. The immunoperoxidase infectivity assay is specific, quantitative, reproducible, and more sensitive than the previously described syncytia induction assay. The immunoperoxidase infectivity assay can be applied to the detection of BLV-infected cells and provides a reliable method for the direct diagnosis of BLV infection in cattle."}
{"id": "PMID:225013", "title": "Lymphocyte transformation for the detection of herpesvirus-induced tumor-associated antigens.", "content": "Cell-mediated immunity to fibroblasts transformed by herpes simplex virus type 2 was investigated with a lymphocyte assay system. The assay system was first standardized with phytohemagglutinin, a nonspecific stimulator of blastogenesis. Hamster splenic and blood lymphocytes reacted to phytohemagglutinin with a dose-response curve similar to that reported for other rodent species. Splenic lymphocytes from hamsters bearing isografts, induced by herpes simplex virus type 2, were transformed by cell-free virus-induced tumor antigens. The reactions with cell-free tumor antigens were dose-dependent and paralleled the findings with phytohemagglutinin. The initial transformation response of immune lymphocytes to homologous tumor antigens occurred after 72 hr incubation with antigen. Immune splenic lymphocytes from hamsters were also significantly stimulated with antigens obtained from cells productively infected with herpes simplex virus type 2. Immune lymphocytes were not stimulated with heterologous antigens from simian virus 40-transformed mouse or hamster cells. Likewise, lymphocytes from hamsters sensitized to cells transformed by simian virus 40 reacted with both simian virus 40-transformed mouse and hamster cells but did not react with cells transformed by a heterologous virus. The results suggest that under defined conditions a lymphocyte transformation assay may be useful for the specific detection of common viral-induced antigens on tumor cells.", "contents": "Lymphocyte transformation for the detection of herpesvirus-induced tumor-associated antigens. Cell-mediated immunity to fibroblasts transformed by herpes simplex virus type 2 was investigated with a lymphocyte assay system. The assay system was first standardized with phytohemagglutinin, a nonspecific stimulator of blastogenesis. Hamster splenic and blood lymphocytes reacted to phytohemagglutinin with a dose-response curve similar to that reported for other rodent species. Splenic lymphocytes from hamsters bearing isografts, induced by herpes simplex virus type 2, were transformed by cell-free virus-induced tumor antigens. The reactions with cell-free tumor antigens were dose-dependent and paralleled the findings with phytohemagglutinin. The initial transformation response of immune lymphocytes to homologous tumor antigens occurred after 72 hr incubation with antigen. Immune splenic lymphocytes from hamsters were also significantly stimulated with antigens obtained from cells productively infected with herpes simplex virus type 2. Immune lymphocytes were not stimulated with heterologous antigens from simian virus 40-transformed mouse or hamster cells. Likewise, lymphocytes from hamsters sensitized to cells transformed by simian virus 40 reacted with both simian virus 40-transformed mouse and hamster cells but did not react with cells transformed by a heterologous virus. The results suggest that under defined conditions a lymphocyte transformation assay may be useful for the specific detection of common viral-induced antigens on tumor cells."}
{"id": "PMID:225015", "title": "Enhanced transformation of xeroderma pigmentosum variant cells by ultraviolet light-irradiated simian virus 40.", "content": "The role of DNA repair in transformation was investigated by infecting repair-deficient xeroderma pigmentosum (XP) variant cells, XP variant heterozygous cells, and normal human fibroblasts with simian virus 40 which had been irradiated by ultraviolet light. The transformation frequencies obtained were compared to those observed for unirradiated virus. While normal and heterozygous cells showed no differences between transformation frequencies using either irradiated or untreated virus, two XP variant cell lines were transformed 2- to 7-fold more readily with irradiated virus than with unirradiated virus. XP variant cells were also found to produce lower than normal quantities of virus following infection with either damages or undamaged virus, suggesting that increased viral production was not contributing to the increased transformation seen for these cells. Finally, the proportion of cells which repair ultraviolet light-irradiated simian virus 40 was found to be similar for wild-type and XP variant cells, suggesting that enhanced transformation in the mutant cells was not associated with a reduction in the numbers of cells which repair damaged virus. Several possible mechanisms to account for the increased transformation of XP variant cells by ultraviolet light-irradiated simian virus 40 are proposed.", "contents": "Enhanced transformation of xeroderma pigmentosum variant cells by ultraviolet light-irradiated simian virus 40. The role of DNA repair in transformation was investigated by infecting repair-deficient xeroderma pigmentosum (XP) variant cells, XP variant heterozygous cells, and normal human fibroblasts with simian virus 40 which had been irradiated by ultraviolet light. The transformation frequencies obtained were compared to those observed for unirradiated virus. While normal and heterozygous cells showed no differences between transformation frequencies using either irradiated or untreated virus, two XP variant cell lines were transformed 2- to 7-fold more readily with irradiated virus than with unirradiated virus. XP variant cells were also found to produce lower than normal quantities of virus following infection with either damages or undamaged virus, suggesting that increased viral production was not contributing to the increased transformation seen for these cells. Finally, the proportion of cells which repair ultraviolet light-irradiated simian virus 40 was found to be similar for wild-type and XP variant cells, suggesting that enhanced transformation in the mutant cells was not associated with a reduction in the numbers of cells which repair damaged virus. Several possible mechanisms to account for the increased transformation of XP variant cells by ultraviolet light-irradiated simian virus 40 are proposed."}
{"id": "PMID:225017", "title": "Ornithine decarboxylase activity, cell proliferation, and tumor promotion in mouse epidermis in vivo.", "content": "The effect of different phorbol esters and of mechanical treatment on the activity of ornithine decarboxylase in mouse epidermis in vivo was investigated. The strong promoter 12-O-tetradecanoylphorbol-13-acetate as well as the weak promoters phorbol dibenzoate and the 12-O-tetradecanoylphorbol-13-acetate analog 12-O-tetradeca-2-cis, 4-trans-6,8-tetraenoylphorobol-13-acetate strongly increased the activity of the enzyme and the intraepidermal level of putrescine, with a maximum at 5 hr after application, when applied in doses which evoke comparable proliferative and irritant responses in skin. The hyperplasiogenic but nonirritant and almost nonpromoting 4-O-methyl ether of 12-O-tetradecanoylphorbol-13-acetate did not show such effects. Mechanical removal of the uppermost horny layer led to a considerable increase of ornithine decarboxylase activity after 4 to 8 hr, while skin massage showed only a minute effect under conditions in which both treatments exhibit about the same mitogenic efficiency. Neither manipulation promotes tumor development. After skin massage, the induction of ornithine decarboxylase was influenced neither by treatments which alter the cyclic adenosine 3',5'-monophosphate level in epidermis (inhibition of phosphodiesterase, beta-adrenergic stimulation, and injection of dibutyryl cyclic adenosine 3',5'-monophosphate) nor by injection of epidermal G1 chalone. The results indicate that no clear-cut correlation exists between epithelial cell proliferation, development of hyperplasia, and tumor promotion on the one hand and an activation of epidermal ornithine decarboxylase on the other.", "contents": "Ornithine decarboxylase activity, cell proliferation, and tumor promotion in mouse epidermis in vivo. The effect of different phorbol esters and of mechanical treatment on the activity of ornithine decarboxylase in mouse epidermis in vivo was investigated. The strong promoter 12-O-tetradecanoylphorbol-13-acetate as well as the weak promoters phorbol dibenzoate and the 12-O-tetradecanoylphorbol-13-acetate analog 12-O-tetradeca-2-cis, 4-trans-6,8-tetraenoylphorobol-13-acetate strongly increased the activity of the enzyme and the intraepidermal level of putrescine, with a maximum at 5 hr after application, when applied in doses which evoke comparable proliferative and irritant responses in skin. The hyperplasiogenic but nonirritant and almost nonpromoting 4-O-methyl ether of 12-O-tetradecanoylphorbol-13-acetate did not show such effects. Mechanical removal of the uppermost horny layer led to a considerable increase of ornithine decarboxylase activity after 4 to 8 hr, while skin massage showed only a minute effect under conditions in which both treatments exhibit about the same mitogenic efficiency. Neither manipulation promotes tumor development. After skin massage, the induction of ornithine decarboxylase was influenced neither by treatments which alter the cyclic adenosine 3',5'-monophosphate level in epidermis (inhibition of phosphodiesterase, beta-adrenergic stimulation, and injection of dibutyryl cyclic adenosine 3',5'-monophosphate) nor by injection of epidermal G1 chalone. The results indicate that no clear-cut correlation exists between epithelial cell proliferation, development of hyperplasia, and tumor promotion on the one hand and an activation of epidermal ornithine decarboxylase on the other."}
{"id": "PMID:225019", "title": "The potential histogenic relationship of the peripheral nerve to synovioma.", "content": "The belief that synoviomas differentiate from the synovial membrane has been widely accepted. Absolute proof is lacking, mainly because precancerous synovial atypia has not been documented in human tissue. During the last 50 years, pain has emerged as one of the significant features of synovioma, occurring very early in the course of the disease in some patients. Gross relationship to nerve, cumulative histological data, and theoretical relationships with three other cancers of neural origin suggest the nerve sheath as an alternate parent tissue for synovioma. Three cases illustrating nerve involvement are included.", "contents": "The potential histogenic relationship of the peripheral nerve to synovioma. The belief that synoviomas differentiate from the synovial membrane has been widely accepted. Absolute proof is lacking, mainly because precancerous synovial atypia has not been documented in human tissue. During the last 50 years, pain has emerged as one of the significant features of synovioma, occurring very early in the course of the disease in some patients. Gross relationship to nerve, cumulative histological data, and theoretical relationships with three other cancers of neural origin suggest the nerve sheath as an alternate parent tissue for synovioma. Three cases illustrating nerve involvement are included."}
{"id": "PMID:225020", "title": "Incorporation of HLA antigens into the envelope of RNA tumor viruses grown in human cells.", "content": "Virion antigens of feline leukemia virus are associated with HLA antigens in the membrane of human cells infected with the virus. Feline leukemia virus produced by these cells incorporates host membrane antigens into the virion envelope, making the virus susceptible to lysis by antisera directed to HLA or to uninfected cells plus complement.", "contents": "Incorporation of HLA antigens into the envelope of RNA tumor viruses grown in human cells. Virion antigens of feline leukemia virus are associated with HLA antigens in the membrane of human cells infected with the virus. Feline leukemia virus produced by these cells incorporates host membrane antigens into the virion envelope, making the virus susceptible to lysis by antisera directed to HLA or to uninfected cells plus complement."}
{"id": "PMID:225021", "title": "Defective reactivation of ultraviolet light-irradiated herpesvirus by a Bloom's syndrome fibroblast strain.", "content": "We have used the technique of host cell reactivation of UV-irradiated herpes simplex virus type 1 as a measure of the repair capacity of three Bloom's syndrome skin fibroblast strains. At low multiplicity of infection (less than 6 x 10(-4) plaque-forming unit/cell), reactivation of the virus by the Bloom's syndrome strains was indistinguishable from that by normal strains. Reactivation at higher multiplicities was measured using an infectious centers assay. At 3 plaque-forming units/cell, survival of UV-irradiated herpes simplex virus was higher in all cell strains as a result of the multiplicity reactivation effect. This effect was, however, much smaller in one Bloom's syndrome strain, GM1492, than in either the normal strains or the other Bloom's syndrome fibroblasts. The defect in GM1492 was manifest only at relatively high multiplicates of infection. Thus, at 0.01 plaque-forming unit/cell, the GM1492 strain appeared normal, using the infectious centers assay. Clonal survival of the UV-irradiated GM1492 fibroblasts was also normal. Caffeine at 4 mM had little effect on either virus or cell survival following UV irradiation. The results indicate that the Bloom's syndrome strain GM1492 may be deficient in one of the cellular functions responsible for the multiplicity reactivation effect. These effects include complementation and recombinational events. Alternatively, the GM1492 strain may have a defective UV repair system which becomes saturated at high levels of damage.", "contents": "Defective reactivation of ultraviolet light-irradiated herpesvirus by a Bloom's syndrome fibroblast strain. We have used the technique of host cell reactivation of UV-irradiated herpes simplex virus type 1 as a measure of the repair capacity of three Bloom's syndrome skin fibroblast strains. At low multiplicity of infection (less than 6 x 10(-4) plaque-forming unit/cell), reactivation of the virus by the Bloom's syndrome strains was indistinguishable from that by normal strains. Reactivation at higher multiplicities was measured using an infectious centers assay. At 3 plaque-forming units/cell, survival of UV-irradiated herpes simplex virus was higher in all cell strains as a result of the multiplicity reactivation effect. This effect was, however, much smaller in one Bloom's syndrome strain, GM1492, than in either the normal strains or the other Bloom's syndrome fibroblasts. The defect in GM1492 was manifest only at relatively high multiplicates of infection. Thus, at 0.01 plaque-forming unit/cell, the GM1492 strain appeared normal, using the infectious centers assay. Clonal survival of the UV-irradiated GM1492 fibroblasts was also normal. Caffeine at 4 mM had little effect on either virus or cell survival following UV irradiation. The results indicate that the Bloom's syndrome strain GM1492 may be deficient in one of the cellular functions responsible for the multiplicity reactivation effect. These effects include complementation and recombinational events. Alternatively, the GM1492 strain may have a defective UV repair system which becomes saturated at high levels of damage."}
{"id": "PMID:225022", "title": "Temperature-dependent alteration in immunogenicity of tumor-associated transplantation antigen monitored via paraformaldehyde fixation.", "content": "Paraformaldehyde-fixed mKSA tumor cells of BALB/c mice were shown to retain tumor-associated transplantation antigen (TATA) activity to a degree comparable to that of X-ray-inactivated tumor cells under the optimal conditions of 1% paraformaldehyde for 30 min at 37 degrees. Unexpectedly, the TATA activity of cells fixed below 10 degrees was greatly reduced. This temperature effect was reversible. TATA activity was restored if the cells were returned to 37 degrees before fixation. Fixation at all temperatures for longer than 2 hr or at paraformaldehyde concentrations greater than 1% also caused a decrease in immunogenicity. Spleen cells from mice immunized with tumor cells fixed at 37 degrees were able to more effectively neutralize tumor growth in the Winn assay compared with those from mice immunized with cells fixed at 0 degrees. Immunization with paraformaldehyde-fixed tumor cells was completely specific. Mice immunized with an antigenically unrelated tumor were not rendered immune to tumor challenge. Fixed tumor cells could be stored for at least 1 month without loss of TATA activity.", "contents": "Temperature-dependent alteration in immunogenicity of tumor-associated transplantation antigen monitored via paraformaldehyde fixation. Paraformaldehyde-fixed mKSA tumor cells of BALB/c mice were shown to retain tumor-associated transplantation antigen (TATA) activity to a degree comparable to that of X-ray-inactivated tumor cells under the optimal conditions of 1% paraformaldehyde for 30 min at 37 degrees. Unexpectedly, the TATA activity of cells fixed below 10 degrees was greatly reduced. This temperature effect was reversible. TATA activity was restored if the cells were returned to 37 degrees before fixation. Fixation at all temperatures for longer than 2 hr or at paraformaldehyde concentrations greater than 1% also caused a decrease in immunogenicity. Spleen cells from mice immunized with tumor cells fixed at 37 degrees were able to more effectively neutralize tumor growth in the Winn assay compared with those from mice immunized with cells fixed at 0 degrees. Immunization with paraformaldehyde-fixed tumor cells was completely specific. Mice immunized with an antigenically unrelated tumor were not rendered immune to tumor challenge. Fixed tumor cells could be stored for at least 1 month without loss of TATA activity."}
{"id": "PMID:225024", "title": "A thymus cell marker in murine leukemia virus-induced lymphomas of rats.", "content": "A specific marker for an immature population of thymus cells in the rat was shown by the rosette formation between thymus cells and guinea pig erythrocytes. This method was used to classify murine leukemia virus-induced rat lymphomas. Eight of nine Gross virus-induced rat lymphoma lines, which originated in the thymus, formed rosettes; whereas Friend, Rauscher, or Moloney virus-induced rat lymphoma lines, which originated in either the thymus, spleen, or mesenteric lymph nodes, did not form rosettes. The percentage of the total cells which formed rosettes in the Gross lymphoma lines decreased with in vivo passages. If the tumor cells were exposed to trypsin treatment, then the tumor cells would form rosettes. Lymphoma lines which lacked rosette-forming cells did not show rosette formation after trypsin treatment. An immunofluorescence test showed that none of the lymphoma lines induced by Gross, Friend, Rauscher, or Moloney viruses carried the surface immunoglobulin characteristic of B-cells. These results suggest that Gross lymphomas may be derived from the thymic cortex and that Friend, Rauscher, or Moloney lymphomas may be derived from either mature thymus cells (non-rosette-forming cells) or from a subpopulation of the B-cell series which does not have the surface immunoglobulin G receptor.", "contents": "A thymus cell marker in murine leukemia virus-induced lymphomas of rats. A specific marker for an immature population of thymus cells in the rat was shown by the rosette formation between thymus cells and guinea pig erythrocytes. This method was used to classify murine leukemia virus-induced rat lymphomas. Eight of nine Gross virus-induced rat lymphoma lines, which originated in the thymus, formed rosettes; whereas Friend, Rauscher, or Moloney virus-induced rat lymphoma lines, which originated in either the thymus, spleen, or mesenteric lymph nodes, did not form rosettes. The percentage of the total cells which formed rosettes in the Gross lymphoma lines decreased with in vivo passages. If the tumor cells were exposed to trypsin treatment, then the tumor cells would form rosettes. Lymphoma lines which lacked rosette-forming cells did not show rosette formation after trypsin treatment. An immunofluorescence test showed that none of the lymphoma lines induced by Gross, Friend, Rauscher, or Moloney viruses carried the surface immunoglobulin characteristic of B-cells. These results suggest that Gross lymphomas may be derived from the thymic cortex and that Friend, Rauscher, or Moloney lymphomas may be derived from either mature thymus cells (non-rosette-forming cells) or from a subpopulation of the B-cell series which does not have the surface immunoglobulin G receptor."}
{"id": "PMID:225025", "title": "Influence of adrenal corticosteroids on the susceptibility of cats to feline leukemia virus infection.", "content": "The natural resistance of adult specific-pathogen-free cats to feline leukemia virus (FeLV) was abrogated by treatment with various doses of a synthetic corticosteroid, methylprednisolone acetate (MPA), prior to either oral-nasal or i.p. inoculation of FeLV. Persistent viremia was induced in 82% (18 of 22) of MPA-treated cats versus 11% (1 of 9) of age-matched control cats. MPA-treated FeLV-inoculated cats developed prolonged lymphopenia (2 to 8 weeks postinoculation) and a delayed antibody response to the feline oncornavirus-associated cell membrane antigen. The distribution of FeLV group specific antigen in tissues of MPA-treated, FeLV-inoculated cats suggested that corticosteroids enhanced susceptibility to FeLV by impairing early viral containment in the reticuloendothelial and lymphoid tissues.", "contents": "Influence of adrenal corticosteroids on the susceptibility of cats to feline leukemia virus infection. The natural resistance of adult specific-pathogen-free cats to feline leukemia virus (FeLV) was abrogated by treatment with various doses of a synthetic corticosteroid, methylprednisolone acetate (MPA), prior to either oral-nasal or i.p. inoculation of FeLV. Persistent viremia was induced in 82% (18 of 22) of MPA-treated cats versus 11% (1 of 9) of age-matched control cats. MPA-treated FeLV-inoculated cats developed prolonged lymphopenia (2 to 8 weeks postinoculation) and a delayed antibody response to the feline oncornavirus-associated cell membrane antigen. The distribution of FeLV group specific antigen in tissues of MPA-treated, FeLV-inoculated cats suggested that corticosteroids enhanced susceptibility to FeLV by impairing early viral containment in the reticuloendothelial and lymphoid tissues."}
{"id": "PMID:225027", "title": "Interaction of thoracic irradiation and chemotherapy on local control and survival in small cell carcinoma of the lung.", "content": "The records of all patients with small cell carcinoma of the lung seen in the Division of Therapeutic Radiology at The Medical College of Wisconsin from 1971 through 1977 were reviewed. Of 69 patients (34 with limited disease and 35 with extensive disease), 35 received irradiation only, nine received local plus total-body irradiation, and 25 received irradiation plus chemotherapy. In spite of the prompt response of the tumor, 16 of 35 patients who were only irradiated failed locally. Two patients who received local plus total-body irradiation failed in the chest. Only four of 25 irradiation plus chemotherapy patients failed locally in spite of much lower doses of thoracic irradiation. Limited-disease patients who had local control by irradiation had a slight increase (29 vs 22 weeks) in median survival. Patients receiving irradiation plus chemotherapy (three with limited and 22 with extensive disease) survived for a median of 56 weeks if the local tumor was controlled and for a median of 28 weeks if there was local failure. Regardless of therapy, survival beyond the median is greatly influenced by local tumor control.", "contents": "Interaction of thoracic irradiation and chemotherapy on local control and survival in small cell carcinoma of the lung. The records of all patients with small cell carcinoma of the lung seen in the Division of Therapeutic Radiology at The Medical College of Wisconsin from 1971 through 1977 were reviewed. Of 69 patients (34 with limited disease and 35 with extensive disease), 35 received irradiation only, nine received local plus total-body irradiation, and 25 received irradiation plus chemotherapy. In spite of the prompt response of the tumor, 16 of 35 patients who were only irradiated failed locally. Two patients who received local plus total-body irradiation failed in the chest. Only four of 25 irradiation plus chemotherapy patients failed locally in spite of much lower doses of thoracic irradiation. Limited-disease patients who had local control by irradiation had a slight increase (29 vs 22 weeks) in median survival. Patients receiving irradiation plus chemotherapy (three with limited and 22 with extensive disease) survived for a median of 56 weeks if the local tumor was controlled and for a median of 28 weeks if there was local failure. Regardless of therapy, survival beyond the median is greatly influenced by local tumor control."}
{"id": "PMID:225028", "title": "Phase II evaluation of vindesine in patients with non-small cell carcinoma of the lung.", "content": "Fifty-two patients with non-small cell carcinoma of the lung were treated iv with doses of vindesine at 3--4 mg/m2/week iv. Partial responses occurred in all histologic types in ten of 46 adequately treated patients, for an overall response rate of 22%. Patients not previously treated with chemotherapy had a higher response rate than those who had received prior chemotherapy (33% versus 12%). Reversible peripheral neuropathy occurred in all patients, and was generally of a mild to moderate degree. Mild leukopenia was seen frequently, with a median wbc nadir of 2900/mm3. As reported with the older vinca alkaloids, platelet-sparing with occasional episodes of thrombocytosis occurred with vindesine. It is concluded that vindesine is an active agent in non-small cell carcinoma of the lung and that further studies in previously untreated patients are indicated.", "contents": "Phase II evaluation of vindesine in patients with non-small cell carcinoma of the lung. Fifty-two patients with non-small cell carcinoma of the lung were treated iv with doses of vindesine at 3--4 mg/m2/week iv. Partial responses occurred in all histologic types in ten of 46 adequately treated patients, for an overall response rate of 22%. Patients not previously treated with chemotherapy had a higher response rate than those who had received prior chemotherapy (33% versus 12%). Reversible peripheral neuropathy occurred in all patients, and was generally of a mild to moderate degree. Mild leukopenia was seen frequently, with a median wbc nadir of 2900/mm3. As reported with the older vinca alkaloids, platelet-sparing with occasional episodes of thrombocytosis occurred with vindesine. It is concluded that vindesine is an active agent in non-small cell carcinoma of the lung and that further studies in previously untreated patients are indicated."}
{"id": "PMID:225030", "title": "Phase II evaluation of thioTEPA for treatment of central nervous system tumors.", "content": "Nineteen patients with primary malignant gliomas were treated with thioTEPA. It was found to be ineffective in 13 evaluable patients.", "contents": "Phase II evaluation of thioTEPA for treatment of central nervous system tumors. Nineteen patients with primary malignant gliomas were treated with thioTEPA. It was found to be ineffective in 13 evaluable patients."}
{"id": "PMID:225031", "title": "Liproprotein inhibitor of bone marrow cells in tumor-bearing rats.", "content": "The role of a plasma inhibitor of erythropoiesis is evaluated in rats with Walker-256 carcinoma (W-256). Plasma from tumor-bearing rats was treated by gel filtration chromatography (Sephadex G-150) and fractions were combined into four pools on the basis of mol. wt. Inhibitory activity was assayed by adding an aliquot of the plasma fractions to normal rat marrow cells which were cultured for 24 hr with and without erythropoietin. 59Fe-heme synthesis, [3H]thymidine DNA synthesis, and 14C-leucine protein synthesis were studied. The results indicated that cultures containing the high mol. wt. pool (greater than 400,000 daltons) had significantly decreased heme, DNA and protein synthesis. This inhibitor also diminished the response to erythropoietin in polycythemic mice. The lower mol. wt. pool stimulated heme synthesis in vitro. To identify the inhibitor further, plasma lipoprotein classes were isolated by density gradient ultracentrifugation. The very low density lipoprotein (VLDL) and chylomicron fractions markedly inhibited DNA, protein and heme synthesis. Low density and high density lipoprotein fractions were inactive. A lipoprotein inhibitor of erythropoiesis was also identified in cancerous ascitic fluid, and to a lesser degree, in normal rat plasma. We suggest that this VLDL inhibitor of marrow erythropoiesis is a contributing factor in the anaemia of cancer.", "contents": "Liproprotein inhibitor of bone marrow cells in tumor-bearing rats. The role of a plasma inhibitor of erythropoiesis is evaluated in rats with Walker-256 carcinoma (W-256). Plasma from tumor-bearing rats was treated by gel filtration chromatography (Sephadex G-150) and fractions were combined into four pools on the basis of mol. wt. Inhibitory activity was assayed by adding an aliquot of the plasma fractions to normal rat marrow cells which were cultured for 24 hr with and without erythropoietin. 59Fe-heme synthesis, [3H]thymidine DNA synthesis, and 14C-leucine protein synthesis were studied. The results indicated that cultures containing the high mol. wt. pool (greater than 400,000 daltons) had significantly decreased heme, DNA and protein synthesis. This inhibitor also diminished the response to erythropoietin in polycythemic mice. The lower mol. wt. pool stimulated heme synthesis in vitro. To identify the inhibitor further, plasma lipoprotein classes were isolated by density gradient ultracentrifugation. The very low density lipoprotein (VLDL) and chylomicron fractions markedly inhibited DNA, protein and heme synthesis. Low density and high density lipoprotein fractions were inactive. A lipoprotein inhibitor of erythropoiesis was also identified in cancerous ascitic fluid, and to a lesser degree, in normal rat plasma. We suggest that this VLDL inhibitor of marrow erythropoiesis is a contributing factor in the anaemia of cancer."}
{"id": "PMID:225032", "title": "The mechanism of sensory transduction in the sensilla of the trochanteral hair plate of the cockroach, Periplaneta americana.", "content": "The trochanteral hair plate of the cockroach leg contains approximately 60 hair sensilla that are deflected by a joint membrane during flexion of the leg. Previous work has shown that the organ is a mechanoreceptor which limits leg flexion during walking by reflex connections to flexor and extensor motoneurons. Functional analysis of the largest sensilla has shown that their behaviour may be well approximated by a velocity detector followed by a unidirectional rectifier. We report here the results of an examination of the largest sensilla by scanning and transmission electron microscopy in an attempt to correlate the structure with the known functional elements. Each hair is innervated by a single sensory dendrite which is surrounded by an electron dense dendritic sheath. The dendrite terminates below the hair shaft in a tubular body containing a parallel array of microtubules embedded in an electron dense matrix, while the dendritic sheath extends beyond the tubular body to form the walls of the ecdysial canal. At the proximal end of the tubular body the dendritic sheath and sensory dendrite are anchored to the cuticular socket by a fibrous dome which seems to form a flucrum around which the tubular body can be deflected by movements of the hair. We suggest that the basis for the detection of velocity shealth and the tubular body. The structure is also discussed with relation to the mechanism of sensory transduction and the possible causes of the unidirectional sensitivity.", "contents": "The mechanism of sensory transduction in the sensilla of the trochanteral hair plate of the cockroach, Periplaneta americana. The trochanteral hair plate of the cockroach leg contains approximately 60 hair sensilla that are deflected by a joint membrane during flexion of the leg. Previous work has shown that the organ is a mechanoreceptor which limits leg flexion during walking by reflex connections to flexor and extensor motoneurons. Functional analysis of the largest sensilla has shown that their behaviour may be well approximated by a velocity detector followed by a unidirectional rectifier. We report here the results of an examination of the largest sensilla by scanning and transmission electron microscopy in an attempt to correlate the structure with the known functional elements. Each hair is innervated by a single sensory dendrite which is surrounded by an electron dense dendritic sheath. The dendrite terminates below the hair shaft in a tubular body containing a parallel array of microtubules embedded in an electron dense matrix, while the dendritic sheath extends beyond the tubular body to form the walls of the ecdysial canal. At the proximal end of the tubular body the dendritic sheath and sensory dendrite are anchored to the cuticular socket by a fibrous dome which seems to form a flucrum around which the tubular body can be deflected by movements of the hair. We suggest that the basis for the detection of velocity shealth and the tubular body. The structure is also discussed with relation to the mechanism of sensory transduction and the possible causes of the unidirectional sensitivity."}
{"id": "PMID:225033", "title": "Infundibular neurons of the human hypothalamus simultaneously reactive with antisera against endorphins, ACTH, MSH and beta-LPH.", "content": "In man, discrete neurons of the infundibular (arcuate) nucleus contain compounds that can be stained with anti-endorphin (alpha and beta), anti-ACTH, anti-MSH (alpha and beta) and anti-beta-LPH immune sera (I.S.). In the fetus, certain neurons stain with anti-beta-endorphin or anti((17--39)ACTH starting from the 11th week of fetal life. At the ultrastructural level, these neurons contain elementary granules that are immunoreactive with anti-beta-endorphin. In the adult, neurons immunoreactive with anti-beta-endorphin are found in the infundibular nucleus. Their axonal fibers terminate around blood vessels in the neurovascular zone and in the pituitary stalk, or establish contacts with non-immunoreactive perikarya of the infundibular nucleus. These neurons can be stained with anti(17--39)ACTH and anti-beta-endorphin I.S. The most reactive are also stained moderately with anti-alpha-MSH, anti-beta-MSH, anti-beta-LPH, anti-alpha-endorphin, or anti(1--24)ACTH I.S. These results indicate that, in man, compound(s) identical with or immunologically related to endorphins, beta-LPH, ACTH and MSH are secreted by certain hypothalamic neurons. These agents probably originate from a common precursor molecula similar to the so-called pro-opiocortin.", "contents": "Infundibular neurons of the human hypothalamus simultaneously reactive with antisera against endorphins, ACTH, MSH and beta-LPH. In man, discrete neurons of the infundibular (arcuate) nucleus contain compounds that can be stained with anti-endorphin (alpha and beta), anti-ACTH, anti-MSH (alpha and beta) and anti-beta-LPH immune sera (I.S.). In the fetus, certain neurons stain with anti-beta-endorphin or anti((17--39)ACTH starting from the 11th week of fetal life. At the ultrastructural level, these neurons contain elementary granules that are immunoreactive with anti-beta-endorphin. In the adult, neurons immunoreactive with anti-beta-endorphin are found in the infundibular nucleus. Their axonal fibers terminate around blood vessels in the neurovascular zone and in the pituitary stalk, or establish contacts with non-immunoreactive perikarya of the infundibular nucleus. These neurons can be stained with anti(17--39)ACTH and anti-beta-endorphin I.S. The most reactive are also stained moderately with anti-alpha-MSH, anti-beta-MSH, anti-beta-LPH, anti-alpha-endorphin, or anti(1--24)ACTH I.S. These results indicate that, in man, compound(s) identical with or immunologically related to endorphins, beta-LPH, ACTH and MSH are secreted by certain hypothalamic neurons. These agents probably originate from a common precursor molecula similar to the so-called pro-opiocortin."}
{"id": "PMID:225034", "title": "Electron microscopic study of the giant cells in the olfactory bulb of labyrinth fish (Belontiidae, perciformes).", "content": "The giant cells in the olfactory bulb of labyrinth fish, most likely belonging to the nervus terminalis, show ultrastructural features of active synthesis of secretory material. Dense core vesicles (70--100 nm in diameter), found in the perikaryon as well as in the axon, are the possible storage sites of the secretory substance. Its chemical nature is unknown. In some of these vesicles acid phosphatase is demonstrable. Large membrane-bound bodies (up to 2000 nm in diameter), either containing an electron dense matrix or debris of cytoplasmic organelles, are also acid phosphatase-positive, suggesting their lysosomal nature. Some other ultrastructural characteristics of these cells are also described.", "contents": "Electron microscopic study of the giant cells in the olfactory bulb of labyrinth fish (Belontiidae, perciformes). The giant cells in the olfactory bulb of labyrinth fish, most likely belonging to the nervus terminalis, show ultrastructural features of active synthesis of secretory material. Dense core vesicles (70--100 nm in diameter), found in the perikaryon as well as in the axon, are the possible storage sites of the secretory substance. Its chemical nature is unknown. In some of these vesicles acid phosphatase is demonstrable. Large membrane-bound bodies (up to 2000 nm in diameter), either containing an electron dense matrix or debris of cytoplasmic organelles, are also acid phosphatase-positive, suggesting their lysosomal nature. Some other ultrastructural characteristics of these cells are also described."}
{"id": "PMID:225036", "title": "The distribution of endogenous chicken retrovirus sequences in the DNA of galliform birds does not coincide with avian phylogenetic relationships.", "content": "The chicken is a domesticated form of Red Jungle-fowl (Gallus gallus), which belongs to the Pheasant family (Phasianidae) within the order Galliformes. Domestic chickens carry the genome of the endogenous retrovirus RAV-O as DNA sequences integrated into host chromosomes transmitted through the germ line. We have examined the presence and distribution of RAV-O-related sequences in the DNA of Red Junglefowl and other closely related species of Junglefowl, as well as more distantly related Pheasants and Quail. DNA sequences homologous to RAV-O were analyzed by molecular hybridization in liquid and after electrophoresis of restriction endonuclease fragments. The presence of RAV-O-related sequences in avian DNA does not correlate with phylogenetic relationships. Under stringent conditions of hybridization in liquid, DNA sequences homologous to RAV-O cDNA were detected at high levels (greater than 80% homology( only in the genomes of the domestic chicken and its phylogenetic ancestor, the Red Junglefowl (Gallus gallus). The DNA of two other species of Gallus (G. sonnerati, Sonnerat's Junglefowl and G. varius, Green Junglefowl), of Ring-necked Pheasant and of Japanese Quail contained sequences with less than 10% homology to RAV-O cDNA. Under conditions permitting mismatching, however, Ring-necked Pheasant DNA hybridized up to 50% of the RAV-O cDNA, and Quail DNA 24%, whereas the extent of hybridization to Sonnerat's and Green Junglefowl DNA was not markedly increased. Analysis of restriction enzyme digests revealed several distinct fragments of DNA hybridizing to chick retrovirus cDNA in both Red Junglefowl and domestic chicken, and multiple fragments in DNA from two species of Phasianus. No fragments with sequences related to chicken retroviruses were found, however, in digests of DNA prepared from Sonnerat's, Ceylonese and Green Junglefowl, from two other Pheasant genera (Chrysolophus and Lophura), or from one Quail genus (Coturnix). Thus the DNA of three Junglefowl species closely related to Gallus gallus lacked RAV-O sequences while the DNA of more distantly related Phasianus species showed significant homology. These results show that RAV-O-related sequences have not diverged together with the normal host genes during the evolution of the Phasianidae. Although RAV-O sequences are endogenous in all domestic chickens and Red Junglefowl studied thus far, it appears that the RAV-O genome has been introduced relatively recently into the germ line of Gallus gallus, following speciation but before domestication, and independently of the related sequences found in members of the genus Phasianus.", "contents": "The distribution of endogenous chicken retrovirus sequences in the DNA of galliform birds does not coincide with avian phylogenetic relationships. The chicken is a domesticated form of Red Jungle-fowl (Gallus gallus), which belongs to the Pheasant family (Phasianidae) within the order Galliformes. Domestic chickens carry the genome of the endogenous retrovirus RAV-O as DNA sequences integrated into host chromosomes transmitted through the germ line. We have examined the presence and distribution of RAV-O-related sequences in the DNA of Red Junglefowl and other closely related species of Junglefowl, as well as more distantly related Pheasants and Quail. DNA sequences homologous to RAV-O were analyzed by molecular hybridization in liquid and after electrophoresis of restriction endonuclease fragments. The presence of RAV-O-related sequences in avian DNA does not correlate with phylogenetic relationships. Under stringent conditions of hybridization in liquid, DNA sequences homologous to RAV-O cDNA were detected at high levels (greater than 80% homology( only in the genomes of the domestic chicken and its phylogenetic ancestor, the Red Junglefowl (Gallus gallus). The DNA of two other species of Gallus (G. sonnerati, Sonnerat's Junglefowl and G. varius, Green Junglefowl), of Ring-necked Pheasant and of Japanese Quail contained sequences with less than 10% homology to RAV-O cDNA. Under conditions permitting mismatching, however, Ring-necked Pheasant DNA hybridized up to 50% of the RAV-O cDNA, and Quail DNA 24%, whereas the extent of hybridization to Sonnerat's and Green Junglefowl DNA was not markedly increased. Analysis of restriction enzyme digests revealed several distinct fragments of DNA hybridizing to chick retrovirus cDNA in both Red Junglefowl and domestic chicken, and multiple fragments in DNA from two species of Phasianus. No fragments with sequences related to chicken retroviruses were found, however, in digests of DNA prepared from Sonnerat's, Ceylonese and Green Junglefowl, from two other Pheasant genera (Chrysolophus and Lophura), or from one Quail genus (Coturnix). Thus the DNA of three Junglefowl species closely related to Gallus gallus lacked RAV-O sequences while the DNA of more distantly related Phasianus species showed significant homology. These results show that RAV-O-related sequences have not diverged together with the normal host genes during the evolution of the Phasianidae. Although RAV-O sequences are endogenous in all domestic chickens and Red Junglefowl studied thus far, it appears that the RAV-O genome has been introduced relatively recently into the germ line of Gallus gallus, following speciation but before domestication, and independently of the related sequences found in members of the genus Phasianus."}
{"id": "PMID:225037", "title": "The roles of the simian virus 40 tumor antigens in transformation of Chinese hamster lung cells.", "content": "Simian virus 40 mutants and deletions between 0.54 and 0.59 map units direct the synthesis of defective 20K t antigens (Crawford et al., 1978). These deletion mutants transformed actively growing CHL cells nearly as efficently as did wild-type virus, in either the focus formation assay or the growth in soft agar assay. In contrast, when CHL cells were in a resting state during infection, the transformation frequency of the mutants relative to wild-type dropped approximately 50 fold. The presence of the phorbol ester, TPA, diminished this difference. CHL cell lines transformed by the deletion mutants and selected by the focus assay grew almost as efficiently in soft agar as lines transformed by wild-type SV40. Both produced tumors in nude mice. The function of the 20K t antigen is discussed.", "contents": "The roles of the simian virus 40 tumor antigens in transformation of Chinese hamster lung cells. Simian virus 40 mutants and deletions between 0.54 and 0.59 map units direct the synthesis of defective 20K t antigens (Crawford et al., 1978). These deletion mutants transformed actively growing CHL cells nearly as efficently as did wild-type virus, in either the focus formation assay or the growth in soft agar assay. In contrast, when CHL cells were in a resting state during infection, the transformation frequency of the mutants relative to wild-type dropped approximately 50 fold. The presence of the phorbol ester, TPA, diminished this difference. CHL cell lines transformed by the deletion mutants and selected by the focus assay grew almost as efficiently in soft agar as lines transformed by wild-type SV40. Both produced tumors in nude mice. The function of the 20K t antigen is discussed."}
{"id": "PMID:225038", "title": "Loss of integrated viral DNA sequences in polyomatransformed cells is associated with an active viral A function.", "content": "Rat cells transformed by polyoma virus contain, in addition to integrated viral DNA, a small number of nonintegrated viral DNA molecules. The free viral DNA originates from the integrated form through a spontaneous induction of viral DNA replication in a minority of the cell population. Its presence is under the control of the viral A locus. To determine whether the induction of free viral DNA replication was accompanied by a loss of integrated viral DNA molecules in a phenomenon similar to the \"curing\" of lysogenic bacteria, we selected for revertants arising in the transformed rat populations and determined whether these cells had lost integrated viral genomes. We further investigated whether the viral A function was necessary for \"curing\" by determining the frequency of cured cells in populations of rat cells transformed by the ts-a mutant of polyoma virus following propagation at the permissive or nonpermissive temperature. A large proportion of the revertants isolated were negative or weakly positive when assayed by immunofluorescence for polyoma T antigen and were unable to produce infectious virus upon fusion with permissive mouse cells. The T antigen-negative, virus rescue-negative clones can be retransformed by superinfection and appear to have lost a considerable proportion of integrated viral DNA sequences. Restriction enzyme analysis of the integrated viral DNA sequences shows that the parental transformed lines contain tandem repeats of integrated viral molecules, and that this tandem arrangement is generally lost in the cured derivatives. While cells transformed by wild-type virus undergo \"curing\" with about the same frequency at 33 degrees or 39 degrees C, cells transformed by the ts-a mutant contain a much higher frequency of cured cells after propagation at 33 degrees than at 39 degrees C. Our results indicate that in polyoma-transformed rat cells, loss of integrated viral DNA can occur at a rather high rate, producing (at least in some cases) cells which have reverted partially or completely to a normal phenotype. Loss of integrated viral DNA is never total and appears to involve an excision event. The polyoma A function (large T antigen) is necessary for such excision to occur. In the absence of a functional A gene product, the association of the viral DNA with the host DNA appears to be very stable.", "contents": "Loss of integrated viral DNA sequences in polyomatransformed cells is associated with an active viral A function. Rat cells transformed by polyoma virus contain, in addition to integrated viral DNA, a small number of nonintegrated viral DNA molecules. The free viral DNA originates from the integrated form through a spontaneous induction of viral DNA replication in a minority of the cell population. Its presence is under the control of the viral A locus. To determine whether the induction of free viral DNA replication was accompanied by a loss of integrated viral DNA molecules in a phenomenon similar to the \"curing\" of lysogenic bacteria, we selected for revertants arising in the transformed rat populations and determined whether these cells had lost integrated viral genomes. We further investigated whether the viral A function was necessary for \"curing\" by determining the frequency of cured cells in populations of rat cells transformed by the ts-a mutant of polyoma virus following propagation at the permissive or nonpermissive temperature. A large proportion of the revertants isolated were negative or weakly positive when assayed by immunofluorescence for polyoma T antigen and were unable to produce infectious virus upon fusion with permissive mouse cells. The T antigen-negative, virus rescue-negative clones can be retransformed by superinfection and appear to have lost a considerable proportion of integrated viral DNA sequences. Restriction enzyme analysis of the integrated viral DNA sequences shows that the parental transformed lines contain tandem repeats of integrated viral molecules, and that this tandem arrangement is generally lost in the cured derivatives. While cells transformed by wild-type virus undergo \"curing\" with about the same frequency at 33 degrees or 39 degrees C, cells transformed by the ts-a mutant contain a much higher frequency of cured cells after propagation at 33 degrees than at 39 degrees C. Our results indicate that in polyoma-transformed rat cells, loss of integrated viral DNA can occur at a rather high rate, producing (at least in some cases) cells which have reverted partially or completely to a normal phenotype. Loss of integrated viral DNA is never total and appears to involve an excision event. The polyoma A function (large T antigen) is necessary for such excision to occur. In the absence of a functional A gene product, the association of the viral DNA with the host DNA appears to be very stable."}
{"id": "PMID:225039", "title": "The structure of the termini of the DNA of Epstein-Barr virus.", "content": "We have studied the DNA of Epstein-Barr virus (EBV) isolated from the B95-8 strain of that virus (Miller and Lipman, 1973). When EBV DNA is partially digested with lambda-exonuclease and allowed to reanneal, up to 50% of the full-length molecules circularize. The arrangements of nucleotide sequences containing the terminal repeats identified in this circularization experiment have been determined. Those fragments of viral DNA generated by digestion with restriction endonucleases which are terminal and contain the terminal repeats have been identified by their sensitivity to digestion of full-length DNA by lambda-exonuclease and by virtue of their being partially homologous to one another. The population of DNA molecules in the B95-8 strain of EBV was found to be nonuniform. The nonuniformity results from different molecules having different numbers of a 0.37 megadalton terminal repeat at each end. About 70% of molecules have four terminal repeats at one end, while four equal classes, each comprising approximately 25% of the population, have one, two, three or four repeats at the other end. The arrangements of nucleotide sequences identified as being terminal in virion DNA were studied in the intracellular circular viral DNA of cells transformed by a single particle on EBV. All fragments produced by digestion with endonucleases and scored as being terminal in virion DNA were absent from intracellular circular DNA. An additional fragment was identified in the digests of intracellular DNA of each transformed clone. The molecular weights of the new fragments equal the sum of the molecular weights of two terminal fragments which are joined upon intracellular circularization of viral DNA.", "contents": "The structure of the termini of the DNA of Epstein-Barr virus. We have studied the DNA of Epstein-Barr virus (EBV) isolated from the B95-8 strain of that virus (Miller and Lipman, 1973). When EBV DNA is partially digested with lambda-exonuclease and allowed to reanneal, up to 50% of the full-length molecules circularize. The arrangements of nucleotide sequences containing the terminal repeats identified in this circularization experiment have been determined. Those fragments of viral DNA generated by digestion with restriction endonucleases which are terminal and contain the terminal repeats have been identified by their sensitivity to digestion of full-length DNA by lambda-exonuclease and by virtue of their being partially homologous to one another. The population of DNA molecules in the B95-8 strain of EBV was found to be nonuniform. The nonuniformity results from different molecules having different numbers of a 0.37 megadalton terminal repeat at each end. About 70% of molecules have four terminal repeats at one end, while four equal classes, each comprising approximately 25% of the population, have one, two, three or four repeats at the other end. The arrangements of nucleotide sequences identified as being terminal in virion DNA were studied in the intracellular circular viral DNA of cells transformed by a single particle on EBV. All fragments produced by digestion with endonucleases and scored as being terminal in virion DNA were absent from intracellular circular DNA. An additional fragment was identified in the digests of intracellular DNA of each transformed clone. The molecular weights of the new fragments equal the sum of the molecular weights of two terminal fragments which are joined upon intracellular circularization of viral DNA."}
{"id": "PMID:225040", "title": "Structure of the 3' hairpin termini of four rodent parvovirus genomes: nucleotide sequence homology at origins of DNA replication.", "content": "The nucleotide sequences of the 3' termini of the DNA from four autonomous rodent parvoviruses have been determined. The terminus of each genome exists as a Y-shaped hairpin structure involving 115 or 116 nucleotides. The sequence of this region of DNA is highly conserved and shows no evidence of internal sequence heterogeneity, a characteristic which is observed in the terminal nucleotide sequence of the helper-dependent, adeno-associated viruses (Berns et al., 1978a). The implications of these results with respect to the models of parvovirus DNA replication are discussed.", "contents": "Structure of the 3' hairpin termini of four rodent parvovirus genomes: nucleotide sequence homology at origins of DNA replication. The nucleotide sequences of the 3' termini of the DNA from four autonomous rodent parvoviruses have been determined. The terminus of each genome exists as a Y-shaped hairpin structure involving 115 or 116 nucleotides. The sequence of this region of DNA is highly conserved and shows no evidence of internal sequence heterogeneity, a characteristic which is observed in the terminal nucleotide sequence of the helper-dependent, adeno-associated viruses (Berns et al., 1978a). The implications of these results with respect to the models of parvovirus DNA replication are discussed."}
{"id": "PMID:225041", "title": "Sequence of inverted terminal repetitions from different adenoviruses: demonstration of conserved sequences and homology between SA7 termini and SV40 DNA.", "content": "We have established the nucleotide sequence for the inverted terminal repetition of human adenovirus type 3, a subgroup B adenovirus. The repetition, which is 136 bp long, shows a high degree of homology with the known sequence for the inverted repetition of adenovirus type 5 (Steenbergh et al., 1977) a subgroup C adenovirus. Partial sequence information convering 120 bp of the inverted terminal repetitions of human serotype 12, a subgroup A member, and of simian adenovirus type 7 has also been obtained. A comparison of the established sequences shows that the terminal repetitions, in particular the first 50 bp from the ends, contain sequences that have been well conserved in adenovirus evolution. For instance, only six mismatched base pairs were detected among the first 50 bp in the repetitions of simian adenovirus type 7 and human adenovirus type 5, although the homology between simian adenovirus 7 and human subgroup C adenoviruses was estimated to be only 30%. A 14 bp sequence located 9-22 nucleotides from the ends is present in DNAs from all the human serotypes examined as well as in simian adenovirus 7 DNA. Furthermore, the simian adenovirus 7 repetition contains a 21 bp sequence which is present in SV40 DNA, close to the origin of DNA replication.", "contents": "Sequence of inverted terminal repetitions from different adenoviruses: demonstration of conserved sequences and homology between SA7 termini and SV40 DNA. We have established the nucleotide sequence for the inverted terminal repetition of human adenovirus type 3, a subgroup B adenovirus. The repetition, which is 136 bp long, shows a high degree of homology with the known sequence for the inverted repetition of adenovirus type 5 (Steenbergh et al., 1977) a subgroup C adenovirus. Partial sequence information convering 120 bp of the inverted terminal repetitions of human serotype 12, a subgroup A member, and of simian adenovirus type 7 has also been obtained. A comparison of the established sequences shows that the terminal repetitions, in particular the first 50 bp from the ends, contain sequences that have been well conserved in adenovirus evolution. For instance, only six mismatched base pairs were detected among the first 50 bp in the repetitions of simian adenovirus type 7 and human adenovirus type 5, although the homology between simian adenovirus 7 and human subgroup C adenoviruses was estimated to be only 30%. A 14 bp sequence located 9-22 nucleotides from the ends is present in DNAs from all the human serotypes examined as well as in simian adenovirus 7 DNA. Furthermore, the simian adenovirus 7 repetition contains a 21 bp sequence which is present in SV40 DNA, close to the origin of DNA replication."}
{"id": "PMID:225043", "title": "SV40 recombinants carrying rabbit beta-globin gene coding sequences.", "content": "We have constructed and propagated two SV40 recombinants in which different portions of the viral late gene region are replaced by a rabbit beta-globin coding sequence derived from a cloned cDNA (Maniatis et al., 1976). One of these recombinants, which retains the promoter, leader and intervening sequences for a viral late mRNA, directs the synthesis of a stable SV40-globin hybrid transcript. Using a sensitive radioimmunoassay, we have shown that this globin RNA is translated in infected monkey cells. A second recombinant, which retains the late region promoter but lacks the RNA splicing region, produces neither a stable globin transcript nor any detectable beta-globin. These experiments indicate that some sequence within a 500 bp SV40 segment, presumably the splicing region, is required for the accumulation of stable mRNA. They also demonstrate how hybrid transducing viruses can be used both to characterize viral regulatory sequences and to produce new gene products in cultured cells.", "contents": "SV40 recombinants carrying rabbit beta-globin gene coding sequences. We have constructed and propagated two SV40 recombinants in which different portions of the viral late gene region are replaced by a rabbit beta-globin coding sequence derived from a cloned cDNA (Maniatis et al., 1976). One of these recombinants, which retains the promoter, leader and intervening sequences for a viral late mRNA, directs the synthesis of a stable SV40-globin hybrid transcript. Using a sensitive radioimmunoassay, we have shown that this globin RNA is translated in infected monkey cells. A second recombinant, which retains the late region promoter but lacks the RNA splicing region, produces neither a stable globin transcript nor any detectable beta-globin. These experiments indicate that some sequence within a 500 bp SV40 segment, presumably the splicing region, is required for the accumulation of stable mRNA. They also demonstrate how hybrid transducing viruses can be used both to characterize viral regulatory sequences and to produce new gene products in cultured cells."}
{"id": "PMID:225044", "title": "SV40 recombinants carrying a functional RNA splice junction and polyadenylation site from the chromosomal mouse beta maj globin gene.", "content": "We have introduced a fragment of the chromosomal mouse beta major globin gene into SV40 and used the resultant hybrid virus to infect cultured monkey kidney cells. The mouse DNA fragment, which contains an intervening sequence and a poly(A) addition site, has been inserted in both possible orientations relative to the SV40 late region promoter. While the fragment is transcribed regardless of orientation, the RNA splice signal and poly(A) addition site are utilized only when the fragment is inserted in the \"sense\" orientation. Thus genomic mouse signals for both splicing and polyadenylation are recognized across species boundaries. Furthermore, since only an 18 bp segment was included on the 5' border of the intervening sequence, we can define a maximum length for this splice signal.", "contents": "SV40 recombinants carrying a functional RNA splice junction and polyadenylation site from the chromosomal mouse beta maj globin gene. We have introduced a fragment of the chromosomal mouse beta major globin gene into SV40 and used the resultant hybrid virus to infect cultured monkey kidney cells. The mouse DNA fragment, which contains an intervening sequence and a poly(A) addition site, has been inserted in both possible orientations relative to the SV40 late region promoter. While the fragment is transcribed regardless of orientation, the RNA splice signal and poly(A) addition site are utilized only when the fragment is inserted in the \"sense\" orientation. Thus genomic mouse signals for both splicing and polyadenylation are recognized across species boundaries. Furthermore, since only an 18 bp segment was included on the 5' border of the intervening sequence, we can define a maximum length for this splice signal."}
{"id": "PMID:225045", "title": "Effect of organotin compounds and hexachlorophene on brain adenosine cyclic 3',5'-monophosphate metabolism.", "content": "The effect of triethyltin (TET), triphenyltin (TPT), hexachlorophene (HCP) and cuprizone on adenosine cyclic 3',5'-monophosphate (cyclic AMP) production in rat brain was examined both in vitro and in vivo. TET and TPT inhibited basal adenylate cyclase activity of brain homogenate at a concentration as low as 1 microM in vitro but these compounds had no effect on norepinephrine (NE) and dopamine(DA)-stimluated enzyme activity. HCP and cuprizone failed to inhibit adenylate cyclase activity. In vivo TET given intravenously at a dose rate of 10 mg/kg decreased the cyclic AMP content of cerebrum, but not of medulla. TPT and HCP give intravenously and intraperitoneally respectively failed to decrease the cyclic AMP content of the cerebrum. In the case of TET the reduction in cyclic AMP content of the cerebrum was prevented by maintaining the rats normothermic after treatment. On the basis of these results the inhibition of adenylate cyclase produced by TET in brain homogenates in vitro would not appear to be involved in the development of nervous changes associated with acute TET toxicity, or in the production of progressive brain oedema caused by TET, HCP and cuprizone.", "contents": "Effect of organotin compounds and hexachlorophene on brain adenosine cyclic 3',5'-monophosphate metabolism. The effect of triethyltin (TET), triphenyltin (TPT), hexachlorophene (HCP) and cuprizone on adenosine cyclic 3',5'-monophosphate (cyclic AMP) production in rat brain was examined both in vitro and in vivo. TET and TPT inhibited basal adenylate cyclase activity of brain homogenate at a concentration as low as 1 microM in vitro but these compounds had no effect on norepinephrine (NE) and dopamine(DA)-stimluated enzyme activity. HCP and cuprizone failed to inhibit adenylate cyclase activity. In vivo TET given intravenously at a dose rate of 10 mg/kg decreased the cyclic AMP content of cerebrum, but not of medulla. TPT and HCP give intravenously and intraperitoneally respectively failed to decrease the cyclic AMP content of the cerebrum. In the case of TET the reduction in cyclic AMP content of the cerebrum was prevented by maintaining the rats normothermic after treatment. On the basis of these results the inhibition of adenylate cyclase produced by TET in brain homogenates in vitro would not appear to be involved in the development of nervous changes associated with acute TET toxicity, or in the production of progressive brain oedema caused by TET, HCP and cuprizone."}
{"id": "PMID:225049", "title": "Field and experimental studies of poxvirus infections in rodents.", "content": "Data are presented from serological and virological investigations of natural and experimental infections, in rodents, with different poxviruses. The demonstration of poxvirus antibodies (virus neutralizing antibodies, antihaemagglutinins, and precipitins) in the kidneys and/or lungs of rodents from Europe and Africa, and the isolation of poxviruses from them, all indicate that rodents may be poxvirus carriers. Isolates from rodents differed in their properties. Some, from Turkmenistan rodents or from white rats caught near Moscow, appeared to be very close to cowpox virus, while others (from Zaire rodents) were identical to variola-like (whitepox) viruses found earlier in monkeys in the same region. The results suggest that rodents that carry the virus closely similar to cowpox virus might be a source of infection for other animal species.", "contents": "Field and experimental studies of poxvirus infections in rodents. Data are presented from serological and virological investigations of natural and experimental infections, in rodents, with different poxviruses. The demonstration of poxvirus antibodies (virus neutralizing antibodies, antihaemagglutinins, and precipitins) in the kidneys and/or lungs of rodents from Europe and Africa, and the isolation of poxviruses from them, all indicate that rodents may be poxvirus carriers. Isolates from rodents differed in their properties. Some, from Turkmenistan rodents or from white rats caught near Moscow, appeared to be very close to cowpox virus, while others (from Zaire rodents) were identical to variola-like (whitepox) viruses found earlier in monkeys in the same region. The results suggest that rodents that carry the virus closely similar to cowpox virus might be a source of infection for other animal species."}
{"id": "PMID:225051", "title": "[Vasoactive intestinal peptide (VIP): specific receptors and adenylate cyclase activation in a human prolactin-secreting pituitary tumor].", "content": "Receptors for the Vasoactive Intestinal Peptide (VIP) were characterized in particles enriched in plasma membranes obtained from a human prolactin-secreting pituiatry tumor. Native VIP inhibited competitively the binding of 125I-VIP to the particles and stimulated cyclic AMP production; both these effects were observed at concentrations of VIP as low as 10(-11)-10(-10) M, which are compatible with VIP concentrations in the hypothalamopituitary portal blood.", "contents": "[Vasoactive intestinal peptide (VIP): specific receptors and adenylate cyclase activation in a human prolactin-secreting pituitary tumor]. Receptors for the Vasoactive Intestinal Peptide (VIP) were characterized in particles enriched in plasma membranes obtained from a human prolactin-secreting pituiatry tumor. Native VIP inhibited competitively the binding of 125I-VIP to the particles and stimulated cyclic AMP production; both these effects were observed at concentrations of VIP as low as 10(-11)-10(-10) M, which are compatible with VIP concentrations in the hypothalamopituitary portal blood."}
{"id": "PMID:225052", "title": "[Cooperative non-specific binding of the cyclic adenosine 3'--5'-monophosphate receptor protein (CRP) from Escherichia coli to double-stranded thymus and lambda pgal DNA].", "content": "Either free or combined with cAMP, CRP binds cooperatively to double-stranded thymus and lambda pgal DNA. The affinity of CRP for both DNAs in these non-specific interactions is increased by cAMP without noticeable change in the degree of cooperativity. Values of the intrinsic association constant, cooperativity parameter, and site size of DNA were determined from ultracentrifugal investigations under near-physiological ionic conditions.", "contents": "[Cooperative non-specific binding of the cyclic adenosine 3'--5'-monophosphate receptor protein (CRP) from Escherichia coli to double-stranded thymus and lambda pgal DNA]. Either free or combined with cAMP, CRP binds cooperatively to double-stranded thymus and lambda pgal DNA. The affinity of CRP for both DNAs in these non-specific interactions is increased by cAMP without noticeable change in the degree of cooperativity. Values of the intrinsic association constant, cooperativity parameter, and site size of DNA were determined from ultracentrifugal investigations under near-physiological ionic conditions."}
{"id": "PMID:225053", "title": "[Effects of EDTA on (Na+-K+) ATPase bound to human erythrocyte membranes].", "content": "Membranes preincubation with high EDTA concentration induced an alteration on (Na\"-K+) ATPase kinetic behaviour. This effect can be related to a change in calcium content tightly bound to the membranes.", "contents": "[Effects of EDTA on (Na+-K+) ATPase bound to human erythrocyte membranes]. Membranes preincubation with high EDTA concentration induced an alteration on (Na\"-K+) ATPase kinetic behaviour. This effect can be related to a change in calcium content tightly bound to the membranes."}
{"id": "PMID:225054", "title": "Suppression of renin secretion in the rat kidney by a nonvascular alpha-adrenergic mechanism.", "content": "We studied the effect of alpha-adrenergic stimulation, using phenylephrine, on basal and isoproterenol-provoked renin secretion in the isolated perfused rat kidney. Infusion of phenylephrine increased renal perfusion pressure and prevented the response in renin secretion to isoproterenol. No suppression of basal secretion was observed. Renal vasoconstriction was abolished, and the response in renin secretion to isoproterenol was restored by alpha-adrenoceptor blockade with phenoxybenzamine. In contrast, when renal vasoconstriction was prevented by dihydralazine, suppression of renin release by phenylephrine still occurred. These observations support an inhibitory effect of a nonvascular alpha-adrenergic mechanism on renin release. We suggest that the alpha receptor mediating this effect is related directly to the juxtaglomerular cell.", "contents": "Suppression of renin secretion in the rat kidney by a nonvascular alpha-adrenergic mechanism. We studied the effect of alpha-adrenergic stimulation, using phenylephrine, on basal and isoproterenol-provoked renin secretion in the isolated perfused rat kidney. Infusion of phenylephrine increased renal perfusion pressure and prevented the response in renin secretion to isoproterenol. No suppression of basal secretion was observed. Renal vasoconstriction was abolished, and the response in renin secretion to isoproterenol was restored by alpha-adrenoceptor blockade with phenoxybenzamine. In contrast, when renal vasoconstriction was prevented by dihydralazine, suppression of renin release by phenylephrine still occurred. These observations support an inhibitory effect of a nonvascular alpha-adrenergic mechanism on renin release. We suggest that the alpha receptor mediating this effect is related directly to the juxtaglomerular cell."}
{"id": "PMID:225055", "title": "Effect of acetylcholine on the norepinephrine-induced positive chronotropy and increase in cyclic nucleotides of isolated rabbit sinoatrial node.", "content": "Transmural stimulation of, or application of nicotine to, the isolated rabbit sinoatrial (SA) node resulted in initial negative and late positive chronotropy. Simultaneous application of acetylcholine and norepinephrine produced a similar biphasic chronotropic effect. These procedures produced an initial increase in cyclic guanosine 3':5'-monophosphate (cyclic GMP) and a delayed elevation in cyclic adenosine 3':5'-monophosphate (cyclic AMP). The initial and late effects on rate and nucleotide levels were inhibited by pretreatment with atropine and propranolol, respectively. Pretreatment with atropine shortened the time of maximum increase in cyclic AMP level and heart rate from 3 to 1 minute after the simultaneous application of acetylcholine and norepinephrine and enhanced the positive chronotropic effect. Physostigmine prolonged the duration of the increase in cyclic GMP and negative chronotropic effect after the simultaneous application. These results suggest that when acetylocholine and norepinephrine are present simultaneously in the SA node region, the former interacts predominantly with muscarinic receptors and stimulates the cyclic GMP system, which in effect delays the cyclic AMP elevation and reduces the positive chronotropic effect of norepinephrine. However, these effects of acetylcholine cannot be explained solely on the basis of changes in the cyclic GMP level, because sodium nitroprusside produced a marked elevation of the cyclic GMP levels without decreasing the heart rate and did not affect the norepinephrine-induced increase in pacemaker rate and cyclic AMP. Sodium nitroprusside may affect cyclic GMP pools other than those susceptible to acetylcholine. These cyclic GMP pools may not exert chronotropic effects.", "contents": "Effect of acetylcholine on the norepinephrine-induced positive chronotropy and increase in cyclic nucleotides of isolated rabbit sinoatrial node. Transmural stimulation of, or application of nicotine to, the isolated rabbit sinoatrial (SA) node resulted in initial negative and late positive chronotropy. Simultaneous application of acetylcholine and norepinephrine produced a similar biphasic chronotropic effect. These procedures produced an initial increase in cyclic guanosine 3':5'-monophosphate (cyclic GMP) and a delayed elevation in cyclic adenosine 3':5'-monophosphate (cyclic AMP). The initial and late effects on rate and nucleotide levels were inhibited by pretreatment with atropine and propranolol, respectively. Pretreatment with atropine shortened the time of maximum increase in cyclic AMP level and heart rate from 3 to 1 minute after the simultaneous application of acetylcholine and norepinephrine and enhanced the positive chronotropic effect. Physostigmine prolonged the duration of the increase in cyclic GMP and negative chronotropic effect after the simultaneous application. These results suggest that when acetylocholine and norepinephrine are present simultaneously in the SA node region, the former interacts predominantly with muscarinic receptors and stimulates the cyclic GMP system, which in effect delays the cyclic AMP elevation and reduces the positive chronotropic effect of norepinephrine. However, these effects of acetylcholine cannot be explained solely on the basis of changes in the cyclic GMP level, because sodium nitroprusside produced a marked elevation of the cyclic GMP levels without decreasing the heart rate and did not affect the norepinephrine-induced increase in pacemaker rate and cyclic AMP. Sodium nitroprusside may affect cyclic GMP pools other than those susceptible to acetylcholine. These cyclic GMP pools may not exert chronotropic effects."}
{"id": "PMID:225056", "title": "Effects of the oral converting enzyme inhibitor, SQ 14225, in a model of low cardiac output in dogs.", "content": "Dogs with thoracic caval constriction retain sodium and develop ascites and edema. The role of the renin-angiotensin-aldosterone system in this model of low output failure was evaluated before, during, and after administration of the new orally active converting enzyme inhibitor, 2-D-methyl-3-mercaptopropanoyl-L-proline (SQ 14225). The acute response to the initial oral dose of SQ 14225 (10 mg/kg) consisted of a striking fall in plasma aldosterone concentration (PAC) from 22.7 and 29.9 ng% to 10.7, 11.9, and 11.0 ng% (P less than 0.05) after 67.5, 112.5, and 157.5 minutes; sodium excretion increased from 1.9 and 1.9 mu Eq/min to 19.9, 22.4, and 17.8 mu Eq/min. Arterial pressure and filtration fraction decreased (P less than 0.05), and plasma renin activity (PRA) increased (P less than 0.05) after the initial dose of SQ 14225; clearance of paraaminohippuric acid (PAH) and creatinine did not change significantly. The daily responses for 3-4 days to SQ 14225 (35 mg/kg per day, given as doses of 10, 10, and 15 mg/kg) were a decrease in PAC from 50 +/- 15 and 32 +/- 10 ng% to 10 +/- 4 ng% on the 4th day, a value not statistically different from normal (P greater than 0.05), and an increase in sodium excretion from 2.9 to 2.0 mEq/day to 5.7, 10.0, 32.4, and 32.9 mEq/day on a sodium intake of 35 mEq/day (P less than 0.05 for the last 2 days). Arterial pressure and creatinine clearance decreased (P less than 0.05). PRA increased transiently on day 1 of SQ 14225 and then returned toward control levels, and clearance of PAH was unchanged. These data demonstrate an important role for aldosterone and the renin-angiotensin system in the retention of sodium and in ascites formation in dogs with thoracic caval constriction.", "contents": "Effects of the oral converting enzyme inhibitor, SQ 14225, in a model of low cardiac output in dogs. Dogs with thoracic caval constriction retain sodium and develop ascites and edema. The role of the renin-angiotensin-aldosterone system in this model of low output failure was evaluated before, during, and after administration of the new orally active converting enzyme inhibitor, 2-D-methyl-3-mercaptopropanoyl-L-proline (SQ 14225). The acute response to the initial oral dose of SQ 14225 (10 mg/kg) consisted of a striking fall in plasma aldosterone concentration (PAC) from 22.7 and 29.9 ng% to 10.7, 11.9, and 11.0 ng% (P less than 0.05) after 67.5, 112.5, and 157.5 minutes; sodium excretion increased from 1.9 and 1.9 mu Eq/min to 19.9, 22.4, and 17.8 mu Eq/min. Arterial pressure and filtration fraction decreased (P less than 0.05), and plasma renin activity (PRA) increased (P less than 0.05) after the initial dose of SQ 14225; clearance of paraaminohippuric acid (PAH) and creatinine did not change significantly. The daily responses for 3-4 days to SQ 14225 (35 mg/kg per day, given as doses of 10, 10, and 15 mg/kg) were a decrease in PAC from 50 +/- 15 and 32 +/- 10 ng% to 10 +/- 4 ng% on the 4th day, a value not statistically different from normal (P greater than 0.05), and an increase in sodium excretion from 2.9 to 2.0 mEq/day to 5.7, 10.0, 32.4, and 32.9 mEq/day on a sodium intake of 35 mEq/day (P less than 0.05 for the last 2 days). Arterial pressure and creatinine clearance decreased (P less than 0.05). PRA increased transiently on day 1 of SQ 14225 and then returned toward control levels, and clearance of PAH was unchanged. These data demonstrate an important role for aldosterone and the renin-angiotensin system in the retention of sodium and in ascites formation in dogs with thoracic caval constriction."}
{"id": "PMID:225057", "title": "Decreased cardiac beta-adrenergic receptors in deoxycorticosterone-salt and renal hypertensive rats.", "content": "The development of experimental deoxycorticosterone-salt (DOCA-salt) and renal artery clip hypertension in rats is associated with alterations in the sensitivity of the myocardium to adrenergic stimulation. We studied beta-adrenergic receptors and isoproterenol-stimulated adenylate cyclase in myocardial membranes from hypertensive rats to determine whether this altered sensitivity is associated with any change in beta-adrenergic receptors. The specific binding of the beta-adrenergic antagonist, 125I-iodohydroxybenzylpindolol, was used to measure numbers and affinities of receptors in myocardial membrane preparations. Cardiac membranes from both DOCA-salt and renal hypertensive rats showed significantly fewer beta-receptors than did membranes from control, normotensive rats. Receptor affinity remained unchanged. This decrease was from 110 +/- 19 to 49 +/- 5 fmol/mg protein for DOCA-salt hypertension and from 110 +/- 18 to 75 +/- 16 fmol/mg protein for renal artery clip hypertension. Isoproterenol-stimulated adenylate cyclase activity also was lower in membranes from hypertensive rats, whereas basal and fluoride-stimulated activities were unchanged.", "contents": "Decreased cardiac beta-adrenergic receptors in deoxycorticosterone-salt and renal hypertensive rats. The development of experimental deoxycorticosterone-salt (DOCA-salt) and renal artery clip hypertension in rats is associated with alterations in the sensitivity of the myocardium to adrenergic stimulation. We studied beta-adrenergic receptors and isoproterenol-stimulated adenylate cyclase in myocardial membranes from hypertensive rats to determine whether this altered sensitivity is associated with any change in beta-adrenergic receptors. The specific binding of the beta-adrenergic antagonist, 125I-iodohydroxybenzylpindolol, was used to measure numbers and affinities of receptors in myocardial membrane preparations. Cardiac membranes from both DOCA-salt and renal hypertensive rats showed significantly fewer beta-receptors than did membranes from control, normotensive rats. Receptor affinity remained unchanged. This decrease was from 110 +/- 19 to 49 +/- 5 fmol/mg protein for DOCA-salt hypertension and from 110 +/- 18 to 75 +/- 16 fmol/mg protein for renal artery clip hypertension. Isoproterenol-stimulated adenylate cyclase activity also was lower in membranes from hypertensive rats, whereas basal and fluoride-stimulated activities were unchanged."}
{"id": "PMID:225058", "title": "Serum cortisol and 11 deoxycortisol by liquid chromatography: clinical studies and comparison with radioimmunoassay.", "content": "We describe a liquid-chromatographic procedure for separating and measuring cortisol and 11-deoxycortisol in serum. We quantitated these steroids in patients who were undergoing various tests of pituitary and (or) adrenal function and compared the results with those obtained by two radioimmunoassays done in two different laboratories. Results of 48 tests done in 37 functionally normal humans are presented. Cortisol values for sera collected in the morning as determined by liquid chromatography were (mean +/- SD) 134 +/- 54 micrograms/L. Serum cortisol concentrations increased from 136 +/- 65 to 321 +/- 80 micrograms/L 60 min after injecting synthetic corticotropin and increased from 107 +/- 46 to 242 +/- 31 micrograms/L after insulin-induced hypoglycemia. Serum cortisol decreased from 142 +/- 49 to 26 +/- 20 micrograms/L after oral administration of metyrapone, while 11-deoxycortisol increased from less than 10 to 210 +/- 53 micrograms/L. Serum cortisol measured less than 10 micrograms/L the morning after oral ingestion of dexamethasone. Results of the dynamic tests of adrenal function correlated well with previously reported studies. However, the cortisol values obtained by our technique were generally lower than those obtained by radioimmunoassay, possibly owing to lack of specificity of the latter methods used here for comparison. In contrast, values for 11-deoxycortisol were the same by both methods. The present studies confirm the usefulness of liquid chromatography for measuring these two steroids in serum during tests of pituitary and adrenal function. Future refinements of the technique should continue to increase its clinical applications.", "contents": "Serum cortisol and 11 deoxycortisol by liquid chromatography: clinical studies and comparison with radioimmunoassay. We describe a liquid-chromatographic procedure for separating and measuring cortisol and 11-deoxycortisol in serum. We quantitated these steroids in patients who were undergoing various tests of pituitary and (or) adrenal function and compared the results with those obtained by two radioimmunoassays done in two different laboratories. Results of 48 tests done in 37 functionally normal humans are presented. Cortisol values for sera collected in the morning as determined by liquid chromatography were (mean +/- SD) 134 +/- 54 micrograms/L. Serum cortisol concentrations increased from 136 +/- 65 to 321 +/- 80 micrograms/L 60 min after injecting synthetic corticotropin and increased from 107 +/- 46 to 242 +/- 31 micrograms/L after insulin-induced hypoglycemia. Serum cortisol decreased from 142 +/- 49 to 26 +/- 20 micrograms/L after oral administration of metyrapone, while 11-deoxycortisol increased from less than 10 to 210 +/- 53 micrograms/L. Serum cortisol measured less than 10 micrograms/L the morning after oral ingestion of dexamethasone. Results of the dynamic tests of adrenal function correlated well with previously reported studies. However, the cortisol values obtained by our technique were generally lower than those obtained by radioimmunoassay, possibly owing to lack of specificity of the latter methods used here for comparison. In contrast, values for 11-deoxycortisol were the same by both methods. The present studies confirm the usefulness of liquid chromatography for measuring these two steroids in serum during tests of pituitary and adrenal function. Future refinements of the technique should continue to increase its clinical applications."}
{"id": "PMID:225059", "title": "Identification of alpha1-lipoproteins in crossed immunoelectrophoresis.", "content": "Evans Blue dye binds selectively, but with different avidities, to five major antigens in human serum. The anodic mobility of the antigen-dye complexes is greater than that of the antigens alone in crossed immunoelectrophoresis, which is of practical value for identification. We used this characteristic to show that in some human sera there is a population of alpha1-lipoprotein molecules that migrates electrophoretically in the beta-lipoprotein region, where in conventional zone electrophoresis it could be mistaken for beta-lipoprotein. We also demonstrate that horses, unlike rabbits, rarely make precipitins to human serum alpha1-lipoprotein. Equine antiserum to human serum therefore generally is useless for detecting this important serum antigen in immunoelectrophoresis.", "contents": "Identification of alpha1-lipoproteins in crossed immunoelectrophoresis. Evans Blue dye binds selectively, but with different avidities, to five major antigens in human serum. The anodic mobility of the antigen-dye complexes is greater than that of the antigens alone in crossed immunoelectrophoresis, which is of practical value for identification. We used this characteristic to show that in some human sera there is a population of alpha1-lipoprotein molecules that migrates electrophoretically in the beta-lipoprotein region, where in conventional zone electrophoresis it could be mistaken for beta-lipoprotein. We also demonstrate that horses, unlike rabbits, rarely make precipitins to human serum alpha1-lipoprotein. Equine antiserum to human serum therefore generally is useless for detecting this important serum antigen in immunoelectrophoresis."}
{"id": "PMID:225060", "title": "Comparison of two micromethods for determination of lipoprotein cholesterol in plasma.", "content": "We compared the results obtained by a micromethod for the determination of plasma lipoprotein cholesterol, in which electrophoresis is used to separate the lipoprotein fractions (beta-, pre-beta-, and alpha-lipoproteins), with those determinations with ultracentrifugation (low-density, very-low-density, and high-density lipoproteins). Precision of determination (coefficient of variation, CV, %) was the same for beta- and low-density lipoproteins (1.6%), and for pre-beta- and very-low-density lipoproteins (3.7%); however, determination of alpha-lipoprotein cholesterol was more precise (1.4%) than that of high-density lipoprotein cholesterol (3.1%). Analytical recovery of lipoprotein cholesterol was the same for both methods (98--100%) and the results were closely correlated (r = 0.943). The procedure has been used to determine the cholesterol content of plasma lipoprotein fractions of apparently healthy adults (both sexes). Lipoprotein cholesterol concentrations in our population sample compare well with those reported for other groups of similar age, in particular Stanford long-distance runners.", "contents": "Comparison of two micromethods for determination of lipoprotein cholesterol in plasma. We compared the results obtained by a micromethod for the determination of plasma lipoprotein cholesterol, in which electrophoresis is used to separate the lipoprotein fractions (beta-, pre-beta-, and alpha-lipoproteins), with those determinations with ultracentrifugation (low-density, very-low-density, and high-density lipoproteins). Precision of determination (coefficient of variation, CV, %) was the same for beta- and low-density lipoproteins (1.6%), and for pre-beta- and very-low-density lipoproteins (3.7%); however, determination of alpha-lipoprotein cholesterol was more precise (1.4%) than that of high-density lipoprotein cholesterol (3.1%). Analytical recovery of lipoprotein cholesterol was the same for both methods (98--100%) and the results were closely correlated (r = 0.943). The procedure has been used to determine the cholesterol content of plasma lipoprotein fractions of apparently healthy adults (both sexes). Lipoprotein cholesterol concentrations in our population sample compare well with those reported for other groups of similar age, in particular Stanford long-distance runners."}
{"id": "PMID:225061", "title": "1,25-Dihydroxycholecalciferol in human serum and its relationship with other metabolites of vitamin D-3.", "content": "A competitive protein binding assay for 1,25-dihydroxycholecalciferol has been developed using the hormone's nuclear receptor protein from chick intestinal mucosa. This nuclear receptor protein can be stored at -70 degrees C for several months and bound and free hormone can be separated easily with dextran coated charcoal. Results obtained using this assay agree well with those reported by other groups of workers. Serum levels of other vitamin D-3 metabolites, namely 25-hydroxycholecalciferol and 24,25-dihydroxycholecalciferol have also been measured and are shown in relation to 1,25-(OH)2D3 levels.", "contents": "1,25-Dihydroxycholecalciferol in human serum and its relationship with other metabolites of vitamin D-3. A competitive protein binding assay for 1,25-dihydroxycholecalciferol has been developed using the hormone's nuclear receptor protein from chick intestinal mucosa. This nuclear receptor protein can be stored at -70 degrees C for several months and bound and free hormone can be separated easily with dextran coated charcoal. Results obtained using this assay agree well with those reported by other groups of workers. Serum levels of other vitamin D-3 metabolites, namely 25-hydroxycholecalciferol and 24,25-dihydroxycholecalciferol have also been measured and are shown in relation to 1,25-(OH)2D3 levels."}
{"id": "PMID:225062", "title": "Enzymes of collagen biosynthesis in skin and serum in dermatological diseases. I. Enzymes of the skin.", "content": "Immunoreactive prolyl hydroxylase protein, prolyl hydroxylase activity and galactosylhydroxylysyl glucosyltransferase activity were measured in skin biopsies from 54 patients with various dermatological disorders and compared with results from 15 control samples; The mean prolyl hydroxylase activity was significantly elevated in case of keloids (P less than 0.001) and lichen ruber planus (P less than 0.02) and the mean galactosylhydroxylysyl glucosyltransferase activity in keloids (P less than 0.005), lichen ruber planus (P less than 0.02) and psoriasis (P less than 0.05), and high activities of these two enzymes were also occasionally found in other skin diseases and active systemic connective tissue diseases. These two enzyme activities correlated highly significantly (P less than 0.001) with each other in the total disease material. Immunoreactive prolyl hydroxylase protein was significantly elevated in psoriasis (P less than 0.02) lichen ruber planus (P less than 0.005), but not in keloids, where very high activities of the corresponding enzyme were found. Active prolyl hydroxylase constituted about 1.3% of total immunoreactive prolyl hydroxylase protein in normal skin, but as much as 10% in cases of keloids.", "contents": "Enzymes of collagen biosynthesis in skin and serum in dermatological diseases. I. Enzymes of the skin. Immunoreactive prolyl hydroxylase protein, prolyl hydroxylase activity and galactosylhydroxylysyl glucosyltransferase activity were measured in skin biopsies from 54 patients with various dermatological disorders and compared with results from 15 control samples; The mean prolyl hydroxylase activity was significantly elevated in case of keloids (P less than 0.001) and lichen ruber planus (P less than 0.02) and the mean galactosylhydroxylysyl glucosyltransferase activity in keloids (P less than 0.005), lichen ruber planus (P less than 0.02) and psoriasis (P less than 0.05), and high activities of these two enzymes were also occasionally found in other skin diseases and active systemic connective tissue diseases. These two enzyme activities correlated highly significantly (P less than 0.001) with each other in the total disease material. Immunoreactive prolyl hydroxylase protein was significantly elevated in psoriasis (P less than 0.02) lichen ruber planus (P less than 0.005), but not in keloids, where very high activities of the corresponding enzyme were found. Active prolyl hydroxylase constituted about 1.3% of total immunoreactive prolyl hydroxylase protein in normal skin, but as much as 10% in cases of keloids."}
{"id": "PMID:225063", "title": "Enzymes of collagen biosynthesis in skin and serum and dermatological diseases. II. Serum enzymes.", "content": "Serum immunoreactive prolyl hydroxylase protein and galactosylhydroxylysyl glucosyltransferase activity were measured in 54 patients wtih various dermatological diseases and compared with corresponding values in 32 control subjects. These serum enzymes were at the control level in the great majority of the patients, and no correlation was found between serum and skin enzymes, except for one weak correlation in lichen ruber planus. Some patients with psoriasis, lichen ruber planus, keloids, erythema nodosum or chronic discoid lupus erythematosus, however, did have at least one of these enzymes elevated in the serum, and a significant correlation (P less than 0.01) between the two enzymes was found in the total disease material. Thus it does seem that diseases limited only to the skin can sometimes raise these serum enzyme levels. The mean levels of serum immunoreactive prolyl hydroxylase and galactosylhydroxylysyl glucosyltransferase activity were significantly elevated (P less than 0.001) in active systemic connective tissue diseases such as systemic lupus erythematosus, scleroderma or dermatomyositis compared with the controls, and 4 out of 7 values for immunoreactive prolyl hydroxylase and 3 out of 7 for galactosylhydroxylysyl glucosyltransferase activity were above the 95% confidence limit of the controls. Since the levels of the skin enzymes were not elevated in most of these patients, however, the main sources for the elevated serum enzymes were probably tissues other than the skin.", "contents": "Enzymes of collagen biosynthesis in skin and serum and dermatological diseases. II. Serum enzymes. Serum immunoreactive prolyl hydroxylase protein and galactosylhydroxylysyl glucosyltransferase activity were measured in 54 patients wtih various dermatological diseases and compared with corresponding values in 32 control subjects. These serum enzymes were at the control level in the great majority of the patients, and no correlation was found between serum and skin enzymes, except for one weak correlation in lichen ruber planus. Some patients with psoriasis, lichen ruber planus, keloids, erythema nodosum or chronic discoid lupus erythematosus, however, did have at least one of these enzymes elevated in the serum, and a significant correlation (P less than 0.01) between the two enzymes was found in the total disease material. Thus it does seem that diseases limited only to the skin can sometimes raise these serum enzyme levels. The mean levels of serum immunoreactive prolyl hydroxylase and galactosylhydroxylysyl glucosyltransferase activity were significantly elevated (P less than 0.001) in active systemic connective tissue diseases such as systemic lupus erythematosus, scleroderma or dermatomyositis compared with the controls, and 4 out of 7 values for immunoreactive prolyl hydroxylase and 3 out of 7 for galactosylhydroxylysyl glucosyltransferase activity were above the 95% confidence limit of the controls. Since the levels of the skin enzymes were not elevated in most of these patients, however, the main sources for the elevated serum enzymes were probably tissues other than the skin."}
{"id": "PMID:225064", "title": "Apoenzyme of aspartate aminotransferase isozymes in serum and its diagnostic usefullness for hepatic diseases.", "content": "Aspartate aminotransferase in the sera of normal subjects and of patients with hepatic diseases has been immunologically separated into two isoenzymes, cytosolic aspartate aminotransferase and mitochondrial aspartate aminotransferase. The activity of the isoenzymes was measured in three different buffer solutions with or without pyridoxal 5'-phosphate. To attain maximal activation, the apoenzyme of mitochondrial fraction must be preincubated with pyridoxal 5'-phosphate longer than that of the cytosolic fraction in either of the three reaction mixtures. In most sera the activity of both isoenzymes increased substantially in the presence of pyridoxal 5'-phosphate regardless of the type of buffer solutions. Both the apoenzymatic activity and the ratio of apo- to holo-enzymatic activity of each of the isoenzymes varied among samples from the patients with hepatic diseases. However, significantly high ratios of apo- to holo-enzymatic activity of both isoenzymes were observed in the patients with hepatoma in contrast with those with other hepatic diseases. These findings suggest that the simultaneous measurement of both apo- and holo-enzyme activities of aspartate aminotransferase isoenzymes may be useful in the clinical assessment of hepatic diseases.", "contents": "Apoenzyme of aspartate aminotransferase isozymes in serum and its diagnostic usefullness for hepatic diseases. Aspartate aminotransferase in the sera of normal subjects and of patients with hepatic diseases has been immunologically separated into two isoenzymes, cytosolic aspartate aminotransferase and mitochondrial aspartate aminotransferase. The activity of the isoenzymes was measured in three different buffer solutions with or without pyridoxal 5'-phosphate. To attain maximal activation, the apoenzyme of mitochondrial fraction must be preincubated with pyridoxal 5'-phosphate longer than that of the cytosolic fraction in either of the three reaction mixtures. In most sera the activity of both isoenzymes increased substantially in the presence of pyridoxal 5'-phosphate regardless of the type of buffer solutions. Both the apoenzymatic activity and the ratio of apo- to holo-enzymatic activity of each of the isoenzymes varied among samples from the patients with hepatic diseases. However, significantly high ratios of apo- to holo-enzymatic activity of both isoenzymes were observed in the patients with hepatoma in contrast with those with other hepatic diseases. These findings suggest that the simultaneous measurement of both apo- and holo-enzyme activities of aspartate aminotransferase isoenzymes may be useful in the clinical assessment of hepatic diseases."}
{"id": "PMID:225065", "title": "Kinetics of plasma corticosteroids during metyrapone infusion in man.", "content": "The effect of metyrapone on plasma kinetics of cortisol (F), 11-deoxycortisol (S), corticosterone (B), 11-deoxycorticosterone (DOC), aldosterone (Aldo) and 17 hydroxyprogesterone (17 OHP) was studied in ten normal prepubertal children intravenously infused with the drug (1 gm/1.73 m2 body surface area in 4 h). Similar falls in F, B and Aldo were observed during the first hour expressing similar sensitivity of the 11 hydroxylases to the drug. The effect of the compensatory increase of endogenous ACTH could be detected after 1 hour by the rise in 17 OHP. However the concentrations of the 11-hydroxy compounds, F, B and Aldo, remained low throughout the infusion period. From the second hour onwards, facilitation of the synthesis of DOC was noticed. After the end of infusion, the levels of the precursors decreased and F and B were restored to initial values. Aldo remained low probably due to the inhibitory effect of the elevated DOC on the renin-angiotensin system.", "contents": "Kinetics of plasma corticosteroids during metyrapone infusion in man. The effect of metyrapone on plasma kinetics of cortisol (F), 11-deoxycortisol (S), corticosterone (B), 11-deoxycorticosterone (DOC), aldosterone (Aldo) and 17 hydroxyprogesterone (17 OHP) was studied in ten normal prepubertal children intravenously infused with the drug (1 gm/1.73 m2 body surface area in 4 h). Similar falls in F, B and Aldo were observed during the first hour expressing similar sensitivity of the 11 hydroxylases to the drug. The effect of the compensatory increase of endogenous ACTH could be detected after 1 hour by the rise in 17 OHP. However the concentrations of the 11-hydroxy compounds, F, B and Aldo, remained low throughout the infusion period. From the second hour onwards, facilitation of the synthesis of DOC was noticed. After the end of infusion, the levels of the precursors decreased and F and B were restored to initial values. Aldo remained low probably due to the inhibitory effect of the elevated DOC on the renin-angiotensin system."}
{"id": "PMID:225067", "title": "Plasma cyclic-AMP response to parathyroid hormone in Turner's syndrome and Albright's hereditary osteodystrophy.", "content": "Purified bovine parathyroid hormone (BPTH) given by injection to five patients with Turner's syndrome, and seven healthy volunteers produced a significant rise in plasma cyclic AMP reacing a maximum within 10 min. In a pseudohypoparathyroid patient there was no increase. Urinary excretion of cyclic AMP exceeded the normal in three out of four patients with Turner's syndrome. Thus, if there is a relationship between Turner's syndrome and Albright's osteodystrophy it is with the incomplete form known as pseudo-pseudohypoparathyroidism.", "contents": "Plasma cyclic-AMP response to parathyroid hormone in Turner's syndrome and Albright's hereditary osteodystrophy. Purified bovine parathyroid hormone (BPTH) given by injection to five patients with Turner's syndrome, and seven healthy volunteers produced a significant rise in plasma cyclic AMP reacing a maximum within 10 min. In a pseudohypoparathyroid patient there was no increase. Urinary excretion of cyclic AMP exceeded the normal in three out of four patients with Turner's syndrome. Thus, if there is a relationship between Turner's syndrome and Albright's osteodystrophy it is with the incomplete form known as pseudo-pseudohypoparathyroidism."}
{"id": "PMID:225068", "title": "The short metyrapone test: comparison of the plasma ACTH response to metyrapone and insulin-induced hypoglycaemia.", "content": "Plasma ACTH levels in response to metyrapone and insulin hypoglycaemia were compared in subjects with normal pituitary-adrenal function. After a single dose of 2 g of metyrapone given with a snack at midnight, the ACTH level was 468 ng/l +/- 66 )SEM) at 07.30 h the next morning (mean increment approximately nine fold over normal morning values). After insulin-hypoglycaemia the peak ACTH level was 369 ng/l +/- 31 (SEM). Peak ACTH levels greater than 200 ng/l were achieved in twenty of twenty-one (95%) subjects after metyrapone and twenty of twenty-four (83%) after insulin. No major side effects were noted after metyrapone. It is concluded that the short single-dose metyrapone test produces at least as strong and consistent a stimulus to ACTH release as the standard insulin-hypoglycaemia test in normal subjects. A direct assay of ACTH avoids misinterpretations which are inherent in a judgement based on compound S increase only. The short test has significant practical advantages over the classical metyrapone test, and provides a convenient and sensitive method of assessing the negative feedback ACTH control mechanism. It may be particularly useful in detecting minor degrees of pituitary suppression. The value of this test in clinical practice for the investigation of patients with hypothalamic-pituitary diseases in comparison to the classical tests of ACTH stimulation has yet to be demonstrated.", "contents": "The short metyrapone test: comparison of the plasma ACTH response to metyrapone and insulin-induced hypoglycaemia. Plasma ACTH levels in response to metyrapone and insulin hypoglycaemia were compared in subjects with normal pituitary-adrenal function. After a single dose of 2 g of metyrapone given with a snack at midnight, the ACTH level was 468 ng/l +/- 66 )SEM) at 07.30 h the next morning (mean increment approximately nine fold over normal morning values). After insulin-hypoglycaemia the peak ACTH level was 369 ng/l +/- 31 (SEM). Peak ACTH levels greater than 200 ng/l were achieved in twenty of twenty-one (95%) subjects after metyrapone and twenty of twenty-four (83%) after insulin. No major side effects were noted after metyrapone. It is concluded that the short single-dose metyrapone test produces at least as strong and consistent a stimulus to ACTH release as the standard insulin-hypoglycaemia test in normal subjects. A direct assay of ACTH avoids misinterpretations which are inherent in a judgement based on compound S increase only. The short test has significant practical advantages over the classical metyrapone test, and provides a convenient and sensitive method of assessing the negative feedback ACTH control mechanism. It may be particularly useful in detecting minor degrees of pituitary suppression. The value of this test in clinical practice for the investigation of patients with hypothalamic-pituitary diseases in comparison to the classical tests of ACTH stimulation has yet to be demonstrated."}
{"id": "PMID:225069", "title": "Salivary tumours--experience over thirty years.", "content": "A clinicopathological survey of tumours of salivary glands seen in a special surgical clinic at the Christie Hospital and Holt Radium Institute is reported. Nine hundred and seventy-seven benign and malignant tumours have been seen within the past 30 years. The results of treatment are included with particular attention to those of the parotid glands which present the greatest therapeutic problem. The approach to surgical treatment of pleomorphic adenomas is described in detail and guidelines offered as to the procedure that should be used based on full exploration and assessment of each tumour. The need for adjuvant irradiation depends on the standard of surgery that is done. The relationship between carcinomas and benign adenomas is discussed and the need for surgery in all cases is stressed in order to make a definite histological diagnosis in view of the wide range of pathological abnormality encountered.", "contents": "Salivary tumours--experience over thirty years. A clinicopathological survey of tumours of salivary glands seen in a special surgical clinic at the Christie Hospital and Holt Radium Institute is reported. Nine hundred and seventy-seven benign and malignant tumours have been seen within the past 30 years. The results of treatment are included with particular attention to those of the parotid glands which present the greatest therapeutic problem. The approach to surgical treatment of pleomorphic adenomas is described in detail and guidelines offered as to the procedure that should be used based on full exploration and assessment of each tumour. The need for adjuvant irradiation depends on the standard of surgery that is done. The relationship between carcinomas and benign adenomas is discussed and the need for surgery in all cases is stressed in order to make a definite histological diagnosis in view of the wide range of pathological abnormality encountered."}
{"id": "PMID:225073", "title": "Peroneal nerve paralysis: a complication of extensor reconstruction of the knee.", "content": "Adequate hemostasis is extremely important in extensor reconstruction of the knee and possibly all knee injury. Hemarthrosis postoperatively contributes to postoperative discomfort and may increase the risk of infection. Hematoma formation is also responsible for neurovascular complications. Peroneal nerve palsies were associated with hematoma formation in this series and probably represented a pressure palsy. Release of the tourniquet with good hemostasis and a pressure dressing prior to cast application will aid in the prevention of hemarthroses and consequent neurovascular complications. Peroneal nerve palsy is probably more common in reconstruction of the extensor mechanism of the knee than has previously been reported.", "contents": "Peroneal nerve paralysis: a complication of extensor reconstruction of the knee. Adequate hemostasis is extremely important in extensor reconstruction of the knee and possibly all knee injury. Hemarthrosis postoperatively contributes to postoperative discomfort and may increase the risk of infection. Hematoma formation is also responsible for neurovascular complications. Peroneal nerve palsies were associated with hematoma formation in this series and probably represented a pressure palsy. Release of the tourniquet with good hemostasis and a pressure dressing prior to cast application will aid in the prevention of hemarthroses and consequent neurovascular complications. Peroneal nerve palsy is probably more common in reconstruction of the extensor mechanism of the knee than has previously been reported."}
{"id": "PMID:225074", "title": "Metabolic properties of hormonally responsive osteogenic sarcoma cells.", "content": "There is sufficient impetus from the clinical nature of osteogenic sarcoma to stimulate basic studies of the effects of hormones on tumor growth and differentiation. This can probably best be done first by the use of in vitro studies to determine precisely the effects of certain hormones on tumor cell growth and biochemical function. Such investigations would hopefully indicate the direction of in vivo work. The differentiated transplantable tumor described in this paper is clearly hormone-responsive, and offers a means of investigating the effects of other hormones, including growth hormone, androgens, estrogens and glucocorticoids, on specialized function of the osteogenic sarcoma cells, and on the growth of the tumor.", "contents": "Metabolic properties of hormonally responsive osteogenic sarcoma cells. There is sufficient impetus from the clinical nature of osteogenic sarcoma to stimulate basic studies of the effects of hormones on tumor growth and differentiation. This can probably best be done first by the use of in vitro studies to determine precisely the effects of certain hormones on tumor cell growth and biochemical function. Such investigations would hopefully indicate the direction of in vivo work. The differentiated transplantable tumor described in this paper is clearly hormone-responsive, and offers a means of investigating the effects of other hormones, including growth hormone, androgens, estrogens and glucocorticoids, on specialized function of the osteogenic sarcoma cells, and on the growth of the tumor."}
{"id": "PMID:225076", "title": "Reliability of Doppler sonography in extracranial cerebro-vascular stenosis.", "content": "Of our patients who underwent quantitative Doppler sonography (Haemato-Tacho-Graphy), 382 underwent carotid angiography and 61 vertebral artery angiography. The reliability of the method proved to be between 90 and 95 percent for carotid as well as for vertebral arteries. The HTG proved to be a useful addition to angiography in patients with extracranial cerebro-vascular stenosis.", "contents": "Reliability of Doppler sonography in extracranial cerebro-vascular stenosis. Of our patients who underwent quantitative Doppler sonography (Haemato-Tacho-Graphy), 382 underwent carotid angiography and 61 vertebral artery angiography. The reliability of the method proved to be between 90 and 95 percent for carotid as well as for vertebral arteries. The HTG proved to be a useful addition to angiography in patients with extracranial cerebro-vascular stenosis."}
{"id": "PMID:225077", "title": "Atlanto axial rotatory fixation--a cause of torticollis.", "content": "Atlanto-axial rotatory fixation is a rare but important cause of persistent torticollis. The diagnosis is confirmed by careful radiological examination of the atlanto-axial joint, also employing tomography if necessary. Treatment is skull traction in an attempt to improve the position followed by posterior atlanto-axial fusion to prevent further, and potentially disastrous, displacement. Atlanto-axial dislocation or subluxation should be looked for in all cases of acute torticollis, when reduction by traction will most likely be successful and prevent the development of atlanto-axial rotatory fixation and the associated persistent torticollis.", "contents": "Atlanto axial rotatory fixation--a cause of torticollis. Atlanto-axial rotatory fixation is a rare but important cause of persistent torticollis. The diagnosis is confirmed by careful radiological examination of the atlanto-axial joint, also employing tomography if necessary. Treatment is skull traction in an attempt to improve the position followed by posterior atlanto-axial fusion to prevent further, and potentially disastrous, displacement. Atlanto-axial dislocation or subluxation should be looked for in all cases of acute torticollis, when reduction by traction will most likely be successful and prevent the development of atlanto-axial rotatory fixation and the associated persistent torticollis."}
{"id": "PMID:225078", "title": "Lacrimal sweating in a patient with Reader's syndrome.", "content": "A patient is described with a right-sided Reader's syndrome and extensive sweating in the frontal area above the right eye. This pathological sweating can be explained by sprouting of lacrimal parasympathetic fibres in the previous denervated sympathetic sudomotor pathways to that area.", "contents": "Lacrimal sweating in a patient with Reader's syndrome. A patient is described with a right-sided Reader's syndrome and extensive sweating in the frontal area above the right eye. This pathological sweating can be explained by sprouting of lacrimal parasympathetic fibres in the previous denervated sympathetic sudomotor pathways to that area."}
{"id": "PMID:225079", "title": "Uncommon neurological presentations of tuberculoma.", "content": "The neurological manifestations and autopsy findings of 3 cases of tuberculoma have been described. A cerebello-pontine angle tuberculoma presented with a long history of trigeminal neuralgia. Intramedallary tuberculoma of the spinal cord presented with transverse myelitis, history of one complete remission and a normal myelogram. A tuberculoma of the medulla led to, apart from other features, severe orthostatic hypotension. Tuberculous meningitis, as a terminal process, developed in the first two cases and the third patient died from a vasomotor collapse on suddenly standing up from bed.", "contents": "Uncommon neurological presentations of tuberculoma. The neurological manifestations and autopsy findings of 3 cases of tuberculoma have been described. A cerebello-pontine angle tuberculoma presented with a long history of trigeminal neuralgia. Intramedallary tuberculoma of the spinal cord presented with transverse myelitis, history of one complete remission and a normal myelogram. A tuberculoma of the medulla led to, apart from other features, severe orthostatic hypotension. Tuberculous meningitis, as a terminal process, developed in the first two cases and the third patient died from a vasomotor collapse on suddenly standing up from bed."}
{"id": "PMID:225080", "title": "Surgical treatment of traumatic carotid cavernous fistulas.", "content": "Six cases of traumatic corotid cavernous fistulae treated by a combination of trapping and embolization are reported. The advantages and disadvantages of various operative procedures in the treatment of carotid cavernous fistulas are discussed. In our opinion a combination of trapping and embolization has advantages over other methods in the treatment of traumatic carotid cavernous fistulae.", "contents": "Surgical treatment of traumatic carotid cavernous fistulas. Six cases of traumatic corotid cavernous fistulae treated by a combination of trapping and embolization are reported. The advantages and disadvantages of various operative procedures in the treatment of carotid cavernous fistulas are discussed. In our opinion a combination of trapping and embolization has advantages over other methods in the treatment of traumatic carotid cavernous fistulae."}
{"id": "PMID:225082", "title": "Complementary values of static and dynamic scintigraphy, computerized tomography and angiography in the diagnosis of a partially thrombosed giant intracranial aneurysm.", "content": "The case history is presented of a 17 year-old male admitted with right hemiplegia and motor aphasia. Static and dynamic scintigraphy allowed prediction of a giant aneurysm in the deep left frontotemporal region, and this supposition was confirmed by CT and carotid angiography. CT also revealed the aneurysm to extend farther medially than the other two examinations had indicated, the medial portion of the aneurysm being thrombosed. Evaluation of the diagnostic information obtained from the three procedures, combined with the clinical data, makes possible a reconstruction of the probable course of events. The presenting signs were probably caused by a newly formed thrombus within the aneurysm. Death, which occurred after five days, was apparently due to subarachnoid hemorrhage.", "contents": "Complementary values of static and dynamic scintigraphy, computerized tomography and angiography in the diagnosis of a partially thrombosed giant intracranial aneurysm. The case history is presented of a 17 year-old male admitted with right hemiplegia and motor aphasia. Static and dynamic scintigraphy allowed prediction of a giant aneurysm in the deep left frontotemporal region, and this supposition was confirmed by CT and carotid angiography. CT also revealed the aneurysm to extend farther medially than the other two examinations had indicated, the medial portion of the aneurysm being thrombosed. Evaluation of the diagnostic information obtained from the three procedures, combined with the clinical data, makes possible a reconstruction of the probable course of events. The presenting signs were probably caused by a newly formed thrombus within the aneurysm. Death, which occurred after five days, was apparently due to subarachnoid hemorrhage."}
{"id": "PMID:225083", "title": "On the neurology of perception.", "content": "The neurological base of biological space and of spatial perception is discussed. The nervous system is viewed as a system controlling behaviour. Movements as elements of behaviour are guided movements: goal-directed, programmed and ordered in space. Perceptual space is derived from directional properties of behaviour. The sense organs are not 'doors of perception', transparent to the alleged properties of the environment. Rather they are used in a centrifugal sense--outward from the organism. They are instrumental in updating a 'map' of the outside world and of the organisms as part of that world. The map is, in essence, a projection of the organism's own behaviour modified by the regularities, constraints and supports encountered in the world. The role of the periphery varies from moment to moment with the organisational level of behaviour. Thus, the sensomotor system is operated for updating the map and also for calibrating movements. At a peripheral level it helps to level out irregularities encountered in the execution of simple movements. All these functions may take place at the same time. Taken together, these considerations serve as an explanation of the fact that we are able to determine the spatial properties of objects although the shape as such is not presented to the sensory surface of the body, nor are the various scanpaths of our exploratory movements a replica of the geometrical properties of the object.", "contents": "On the neurology of perception. The neurological base of biological space and of spatial perception is discussed. The nervous system is viewed as a system controlling behaviour. Movements as elements of behaviour are guided movements: goal-directed, programmed and ordered in space. Perceptual space is derived from directional properties of behaviour. The sense organs are not 'doors of perception', transparent to the alleged properties of the environment. Rather they are used in a centrifugal sense--outward from the organism. They are instrumental in updating a 'map' of the outside world and of the organisms as part of that world. The map is, in essence, a projection of the organism's own behaviour modified by the regularities, constraints and supports encountered in the world. The role of the periphery varies from moment to moment with the organisational level of behaviour. Thus, the sensomotor system is operated for updating the map and also for calibrating movements. At a peripheral level it helps to level out irregularities encountered in the execution of simple movements. All these functions may take place at the same time. Taken together, these considerations serve as an explanation of the fact that we are able to determine the spatial properties of objects although the shape as such is not presented to the sensory surface of the body, nor are the various scanpaths of our exploratory movements a replica of the geometrical properties of the object."}
{"id": "PMID:225087", "title": "Effects of methylxanthines on the fetus.", "content": "The role of caffeine and other methylxanthines in prematurity, intrauterine growth retardation, and the respiratory distress syndrome is currently under investigation. Their pharmacokinetics are discussed together with their newly discovered beneficial role as possible inhibitors of premature labor and accelerators of fetal lung maturation.", "contents": "Effects of methylxanthines on the fetus. The role of caffeine and other methylxanthines in prematurity, intrauterine growth retardation, and the respiratory distress syndrome is currently under investigation. Their pharmacokinetics are discussed together with their newly discovered beneficial role as possible inhibitors of premature labor and accelerators of fetal lung maturation."}
{"id": "PMID:225088", "title": "Hepatic binding sites for angiotensen II in the rat.", "content": "1. 125I-labelled (Asn1,Val5)-angiotensin II (125I-labelled AII) incubated with purified rat liver membranes was degraded with time, as estimated by three techniques: binding to an excess of specific antibody, polyacrylamide-gel electrophoresis and rebinding to fresh membranes. Degradation was inhibited in the presence of an excess of beta 1-24-corticotrophin but still very marked. 2. 125 I-labelled AII became bound to purified rat liver membranes. Association and dissociation rates were slow. Binding was competitively inhibited by (Asn1,Val5)-AII, (Asp1,Ile5)-AII and (Des,Asp1, Ile5)-AII. Apparent KD was approximately 0.1 nmol/l. 3. Bound hormone was also partly degraded independently of time. 4. Angiotensinases inhibitors had different effects on 125I-labelled AII binding. A clear increase was observed in the presence of beta 1-24-corticotrophin and phenylmethylsulphonylfluoride whereas binding was decreased in the presence of EDTA or 8-hydroxyquinoline. 5. These results demonstrate the presence of high-affinity binding sites for AII and of angiotensinases in hepatic membranes.", "contents": "Hepatic binding sites for angiotensen II in the rat. 1. 125I-labelled (Asn1,Val5)-angiotensin II (125I-labelled AII) incubated with purified rat liver membranes was degraded with time, as estimated by three techniques: binding to an excess of specific antibody, polyacrylamide-gel electrophoresis and rebinding to fresh membranes. Degradation was inhibited in the presence of an excess of beta 1-24-corticotrophin but still very marked. 2. 125 I-labelled AII became bound to purified rat liver membranes. Association and dissociation rates were slow. Binding was competitively inhibited by (Asn1,Val5)-AII, (Asp1,Ile5)-AII and (Des,Asp1, Ile5)-AII. Apparent KD was approximately 0.1 nmol/l. 3. Bound hormone was also partly degraded independently of time. 4. Angiotensinases inhibitors had different effects on 125I-labelled AII binding. A clear increase was observed in the presence of beta 1-24-corticotrophin and phenylmethylsulphonylfluoride whereas binding was decreased in the presence of EDTA or 8-hydroxyquinoline. 5. These results demonstrate the presence of high-affinity binding sites for AII and of angiotensinases in hepatic membranes."}
{"id": "PMID:225090", "title": "Inhibition of mitochondrial electron transfer in rats by ethanethiol and methanethiol.", "content": "1. We have investigated the effects of ethanethiol, methanethiol and dimethyl sulphide on some metabolic processes of isolated rat hepatocytes, isolated mitochondria from liver and brain and ox-heart submitochondrial particles. 2. Ethanethiol, but not dimethyl sulphide, inhibited both gluconeogenesis and ureogenesis from various substrates in rat hepatocytes, depressed cellular ATP content and caused an increased reduction of the mitochondria. 3. Ethanethiol inhibited respiration in isolated rat-liver mitochondria with several substrates, both in the presence of ADP and phosphate or in the presence of an uncoupling agent. Ethanethiol also inhibited respiration in isolated rat-brain mitochondria. Dimethyl sulphide was much less effective in inhibiting mitochondrial respiration. 4. In ox-heart submitochondrial particles ethanethiol inhibited electron transfer between cytochrome c and oxygen. 5. Purified cytochrome c oxidase was inhibited by ethanethiol in a non-competitive manner. 6. Methanethiol inhibited cytochrome c oxidase and was an effective inhibitor of mitochondrial electron transfer, both in liver and brain. 7. The difference in inhibitory properties between ethanethiol, methanethiol and dimethyl sulphide observed in our experiments coincides with the difference in potency to elicit coma in rats. We suggest that inhibition of mitochondrial electron transfer by mercaptans may be relevant to the mechanism by which energy production in brain is depressed during hepatic coma.", "contents": "Inhibition of mitochondrial electron transfer in rats by ethanethiol and methanethiol. 1. We have investigated the effects of ethanethiol, methanethiol and dimethyl sulphide on some metabolic processes of isolated rat hepatocytes, isolated mitochondria from liver and brain and ox-heart submitochondrial particles. 2. Ethanethiol, but not dimethyl sulphide, inhibited both gluconeogenesis and ureogenesis from various substrates in rat hepatocytes, depressed cellular ATP content and caused an increased reduction of the mitochondria. 3. Ethanethiol inhibited respiration in isolated rat-liver mitochondria with several substrates, both in the presence of ADP and phosphate or in the presence of an uncoupling agent. Ethanethiol also inhibited respiration in isolated rat-brain mitochondria. Dimethyl sulphide was much less effective in inhibiting mitochondrial respiration. 4. In ox-heart submitochondrial particles ethanethiol inhibited electron transfer between cytochrome c and oxygen. 5. Purified cytochrome c oxidase was inhibited by ethanethiol in a non-competitive manner. 6. Methanethiol inhibited cytochrome c oxidase and was an effective inhibitor of mitochondrial electron transfer, both in liver and brain. 7. The difference in inhibitory properties between ethanethiol, methanethiol and dimethyl sulphide observed in our experiments coincides with the difference in potency to elicit coma in rats. We suggest that inhibition of mitochondrial electron transfer by mercaptans may be relevant to the mechanism by which energy production in brain is depressed during hepatic coma."}
{"id": "PMID:225091", "title": "The relationship between concentrations of glycosylated haemoglobins and of serum high-density-lipoprotein cholesterol in diabetic patients.", "content": "1. Concentrations of high-density-lipoprotein cholesterol and of glycosylated haemoglobins [HbA1(a+b+c)] were measured in non-fasting blood samples taken from 171 diabetic patients. 2. Mean concentrations of high-density-lipoprotein cholesterol were lower in men, and in patients not requiring insulin. 3. There was no correlation between concentrations of high-density-lipoprotein cholesterol and of HbA1(a+b+c) in the patients as a whole, but a significant positive correlation was found between these values in male diabetics not requiring insulin. 4. Changes in the concentrations of HbA1(a+b+c) were not correlated with changes in concentrations of high-density-lipoprotein cholesterol.", "contents": "The relationship between concentrations of glycosylated haemoglobins and of serum high-density-lipoprotein cholesterol in diabetic patients. 1. Concentrations of high-density-lipoprotein cholesterol and of glycosylated haemoglobins [HbA1(a+b+c)] were measured in non-fasting blood samples taken from 171 diabetic patients. 2. Mean concentrations of high-density-lipoprotein cholesterol were lower in men, and in patients not requiring insulin. 3. There was no correlation between concentrations of high-density-lipoprotein cholesterol and of HbA1(a+b+c) in the patients as a whole, but a significant positive correlation was found between these values in male diabetics not requiring insulin. 4. Changes in the concentrations of HbA1(a+b+c) were not correlated with changes in concentrations of high-density-lipoprotein cholesterol."}
{"id": "PMID:225094", "title": "Effects of aprotinin on renal function and urinary prostaglandin excretion in conscious rats after acute salt loading.", "content": "1. Aprotinin, a potent kallikrein inhibitor, was given to conscious rats with and without expansion of the extracellular fluid volume with isotonic saline. 2. In non-expanded rats aprotinin had no effect on arterial pressure, glomerular filtration rate (GFR), hippuran clearance, urinary flow rate, absolute sodium and potassium excretion or free-water clearance. 3. In volume-expanded rats aprotinin significantly reduced GFR, hippuran clearance, urine volume (V) UNaV, UKV and Cwater/GFR without effect on systemic arterial pressure. 4. Urinary immunoreactive prostaglandin E2 excretion significantly increased during the expansion phase but returned to below the control range during stable extracellular fluid volume expansion. 5. Aprotinin significantly suppressed urinary immunoreactive prostaglandin E2 excretion in non-expanded rats and in volume-expand rats during the expansion phase, but not during stable expansion. 6. The results suggest that the kallikrein-kinin system may contribute to changes in renal function during extracellular volume expansion. This action may not necessarily be associated with changes in renal prostaglandin E2 activity.", "contents": "Effects of aprotinin on renal function and urinary prostaglandin excretion in conscious rats after acute salt loading. 1. Aprotinin, a potent kallikrein inhibitor, was given to conscious rats with and without expansion of the extracellular fluid volume with isotonic saline. 2. In non-expanded rats aprotinin had no effect on arterial pressure, glomerular filtration rate (GFR), hippuran clearance, urinary flow rate, absolute sodium and potassium excretion or free-water clearance. 3. In volume-expanded rats aprotinin significantly reduced GFR, hippuran clearance, urine volume (V) UNaV, UKV and Cwater/GFR without effect on systemic arterial pressure. 4. Urinary immunoreactive prostaglandin E2 excretion significantly increased during the expansion phase but returned to below the control range during stable extracellular fluid volume expansion. 5. Aprotinin significantly suppressed urinary immunoreactive prostaglandin E2 excretion in non-expanded rats and in volume-expand rats during the expansion phase, but not during stable expansion. 6. The results suggest that the kallikrein-kinin system may contribute to changes in renal function during extracellular volume expansion. This action may not necessarily be associated with changes in renal prostaglandin E2 activity."}
{"id": "PMID:225095", "title": "Lecithin-cholesterol acyltransferase and the lipoprotein abnormalities of parenchymal liver disease.", "content": "1. Detailed studies have been made of the plasma lipoprotein abnormalities in parenchymal liver disease to test the hypothesis that the abnormalities would correlate with plasma lecithin-cholesterol acyltransferase (LCAT) activity. 2. When LCAT was high, very-low-density-lipoproteins (VLDL) were normal in composition and had a normal pre-beta electrophoretic mobility. When LCAT was low, VLDL concentrations were greatly reduced. 3. With high LCAT low-density lipoproteins (LDL) were normal. The LDL particles found with low LCAT activity were of normal size but of abnormal composition, being triglyceride rich and cholesteryl ester poor. Regardless of LCAT activity LDL were present in normal amounts. 4. High-density lipoproteins (HDL) were normal in composition and electron-microscopic appearance when LCAT activity was high. When LCAT activity was low HDL were abnormal in composition and 'stacked discs' were seen on electron microscopy. 5. These results suggest that low LCAT activity may be the cause of at least some of the lipoprotein changes of parenchymal liver disease.", "contents": "Lecithin-cholesterol acyltransferase and the lipoprotein abnormalities of parenchymal liver disease. 1. Detailed studies have been made of the plasma lipoprotein abnormalities in parenchymal liver disease to test the hypothesis that the abnormalities would correlate with plasma lecithin-cholesterol acyltransferase (LCAT) activity. 2. When LCAT was high, very-low-density-lipoproteins (VLDL) were normal in composition and had a normal pre-beta electrophoretic mobility. When LCAT was low, VLDL concentrations were greatly reduced. 3. With high LCAT low-density lipoproteins (LDL) were normal. The LDL particles found with low LCAT activity were of normal size but of abnormal composition, being triglyceride rich and cholesteryl ester poor. Regardless of LCAT activity LDL were present in normal amounts. 4. High-density lipoproteins (HDL) were normal in composition and electron-microscopic appearance when LCAT activity was high. When LCAT activity was low HDL were abnormal in composition and 'stacked discs' were seen on electron microscopy. 5. These results suggest that low LCAT activity may be the cause of at least some of the lipoprotein changes of parenchymal liver disease."}
{"id": "PMID:225096", "title": "Brain angiotensin II binding and central [Sar1,Ala8]angiotensin responses in normal rats and the New Zealand strain of genetically hypertensive rats.", "content": "1. Specific angiotensin II (ANGII) receptor binding was measured in regions of the brains of the New Zealand gentically hypertensive and normal rats. 2. ANGII receptor binding was consistently lower in the septum, midbrain, thalamus and posterior medulla of the genetically hypertensive rats than in normal rats. 3. Blood pressure responses to intraventricular injections of ANGII and an ANGII antagonist [Sar1,Ala8]angiotensin were studied in conscious and pentobarbitone-anaesthetized genetically hypertensive and normal rats. In conscious rats no significant difference between the two strains of rat was detected. 4. In pentobarbitone-anaesthetized rats intraventricular injection of 40 microgram of [Sar1,Ala8]angiotensin had a hypotensive effect which was three times greater in the genetically hypertensive rats than that observed in normal rats. The latency of this hypotensive effect was longer than the latency of the hypertensive effect of ANGII. 5. The drinking responses to intraventricular injections of ANGII were similar in genetically hypertensive and normal rats. 6. The physiological role of the ANGII system is discussed and it is concluded that an abnormality of this system in the brain may well be responsible for the hypertension found in the genetically hypertensive rat.", "contents": "Brain angiotensin II binding and central [Sar1,Ala8]angiotensin responses in normal rats and the New Zealand strain of genetically hypertensive rats. 1. Specific angiotensin II (ANGII) receptor binding was measured in regions of the brains of the New Zealand gentically hypertensive and normal rats. 2. ANGII receptor binding was consistently lower in the septum, midbrain, thalamus and posterior medulla of the genetically hypertensive rats than in normal rats. 3. Blood pressure responses to intraventricular injections of ANGII and an ANGII antagonist [Sar1,Ala8]angiotensin were studied in conscious and pentobarbitone-anaesthetized genetically hypertensive and normal rats. In conscious rats no significant difference between the two strains of rat was detected. 4. In pentobarbitone-anaesthetized rats intraventricular injection of 40 microgram of [Sar1,Ala8]angiotensin had a hypotensive effect which was three times greater in the genetically hypertensive rats than that observed in normal rats. The latency of this hypotensive effect was longer than the latency of the hypertensive effect of ANGII. 5. The drinking responses to intraventricular injections of ANGII were similar in genetically hypertensive and normal rats. 6. The physiological role of the ANGII system is discussed and it is concluded that an abnormality of this system in the brain may well be responsible for the hypertension found in the genetically hypertensive rat."}
{"id": "PMID:225106", "title": "DNA-dependent ATPases from Escherichia coli K12.", "content": "Four DNA-dependent ATPases have been isolated from E. coli extracts. ATPases I and III, both sensitive to NEM, require denatured DNA but differ in their heat sensitivity, elution from DEAE-cellulose, and sedimentation coefficient. ATPases II and IV are both resistant to NEM. ATPase II requires partially denatured DNA, whereas ATPase IV can be stimulated by SS DNA. ATPase I is a DNA-unwinding enzyme; ATPase II may be involved in recombination.", "contents": "DNA-dependent ATPases from Escherichia coli K12. Four DNA-dependent ATPases have been isolated from E. coli extracts. ATPases I and III, both sensitive to NEM, require denatured DNA but differ in their heat sensitivity, elution from DEAE-cellulose, and sedimentation coefficient. ATPases II and IV are both resistant to NEM. ATPase II requires partially denatured DNA, whereas ATPase IV can be stimulated by SS DNA. ATPase I is a DNA-unwinding enzyme; ATPase II may be involved in recombination."}
{"id": "PMID:225120", "title": "DNA helicases.", "content": "In summary, we postulate that DNA unwinding and ATP dephosphorylation are coupled in different ways, depending on whether the fibrous ATPase or one of the globular ATPases provides the catalytic agent. Unanswered is the question of whether there is stoichiometry of ATP utilization during the unwinding of a duplex, and unsolved is the role of the individual enzyme in the cell.", "contents": "DNA helicases. In summary, we postulate that DNA unwinding and ATP dephosphorylation are coupled in different ways, depending on whether the fibrous ATPase or one of the globular ATPases provides the catalytic agent. Unanswered is the question of whether there is stoichiometry of ATP utilization during the unwinding of a duplex, and unsolved is the role of the individual enzyme in the cell."}
{"id": "PMID:225122", "title": "Changes in adrenocorticotropic hormone (ACTH) and cortisol levels in drug addicts treated by a new and rapid detoxification procedure using acupuncture and naloxone.", "content": "Plasma ACTH, cortisol, and cyclic-AMP levels of eleven heroin addicts were dertermined before and after treatment with a fast detoxification procedure using acupuncture and electrical stimulation (AES) together with the administration of limited doses of naloxone. At the end of the treatment period, the average plasma ACTH, cortisol, and cyclic-AMP level rose 130,83, and 24 percent, respectively. In view of the appearance of mild withdrawal signs during this method of treatment, the observed increases in ACTH and cortisol levels probably reflect the inability of AES to suppress withdrawal symptoms induced by naloxone completely. The mechanism underlying this new method of treatment is discussed in relation to AES's ability to stimulate the secretion of endorphins.", "contents": "Changes in adrenocorticotropic hormone (ACTH) and cortisol levels in drug addicts treated by a new and rapid detoxification procedure using acupuncture and naloxone. Plasma ACTH, cortisol, and cyclic-AMP levels of eleven heroin addicts were dertermined before and after treatment with a fast detoxification procedure using acupuncture and electrical stimulation (AES) together with the administration of limited doses of naloxone. At the end of the treatment period, the average plasma ACTH, cortisol, and cyclic-AMP level rose 130,83, and 24 percent, respectively. In view of the appearance of mild withdrawal signs during this method of treatment, the observed increases in ACTH and cortisol levels probably reflect the inability of AES to suppress withdrawal symptoms induced by naloxone completely. The mechanism underlying this new method of treatment is discussed in relation to AES's ability to stimulate the secretion of endorphins."}
{"id": "PMID:225124", "title": "Prevalence of neutralizing antibody to the calf rotavirus in New York cattle.", "content": "In March 1973, a modified live virus vaccine was released for sale in the United States for the protection of neonatal calves from infection with calf rotavirus. At that time no published evidence existed that this agent was present in New York or the New England states. Serum neutralizing antibodies for the calf rotavirus (reovirus-like agent of neonatal calf diarrhea) were detected in serum from 108 of 110 dairy cattle in New York State representing 78 different herds. To exclude the possibility that the demonstrated serologic response may have been stimulated by vaccine virus, 36 samples were included that had been collected prior to the date of vaccine release. Neutralizing antibodies were demonstrated in 108 of the 110 sera ranging from titers of 4 to greater than 1024, thereby offering indirect evidence of the ubiquitous nature of calf rotavirus in New York.", "contents": "Prevalence of neutralizing antibody to the calf rotavirus in New York cattle. In March 1973, a modified live virus vaccine was released for sale in the United States for the protection of neonatal calves from infection with calf rotavirus. At that time no published evidence existed that this agent was present in New York or the New England states. Serum neutralizing antibodies for the calf rotavirus (reovirus-like agent of neonatal calf diarrhea) were detected in serum from 108 of 110 dairy cattle in New York State representing 78 different herds. To exclude the possibility that the demonstrated serologic response may have been stimulated by vaccine virus, 36 samples were included that had been collected prior to the date of vaccine release. Neutralizing antibodies were demonstrated in 108 of the 110 sera ranging from titers of 4 to greater than 1024, thereby offering indirect evidence of the ubiquitous nature of calf rotavirus in New York."}
{"id": "PMID:225125", "title": "Short-term immobilization of healthy men: right ventricular function and metabolism during graded exercise.", "content": "Five healthy male volunteers were subjected to graded exercise tests on a bicycle ergometer (600 kpm/min for 8 minutes) with simultaneous catheterization of the right cardiac ventricle and radial artery, first before immobilization and them after five-day bed rest in the head-down posture (the foot bed end was elevated 4.5 degrees). After immobilization, during exercise the stroke index did not increase, the tachycardia was more marked, the indicators of right ventricular contractility increased [+ max dp/dt, mas (dp/dt) /P, --mas dp/dt], the arterial pressure decreased, and the lactic acid level in mixed venous blood rose. Possible causes of haemodynamic and metabolic alterations, occurring in healthy volunteers during graded exercise following short-term hypokinesis, are discussed.", "contents": "Short-term immobilization of healthy men: right ventricular function and metabolism during graded exercise. Five healthy male volunteers were subjected to graded exercise tests on a bicycle ergometer (600 kpm/min for 8 minutes) with simultaneous catheterization of the right cardiac ventricle and radial artery, first before immobilization and them after five-day bed rest in the head-down posture (the foot bed end was elevated 4.5 degrees). After immobilization, during exercise the stroke index did not increase, the tachycardia was more marked, the indicators of right ventricular contractility increased [+ max dp/dt, mas (dp/dt) /P, --mas dp/dt], the arterial pressure decreased, and the lactic acid level in mixed venous blood rose. Possible causes of haemodynamic and metabolic alterations, occurring in healthy volunteers during graded exercise following short-term hypokinesis, are discussed."}
{"id": "PMID:225130", "title": "Simultaneous infection with Treponema pallidum and herpes simplex virus.", "content": "Two cases are presented of simultaneous infection with Treponema pallidum and herpes simplex virus. The occasional concurrence of these diseases suggests that all cases of herpes genitalis, including those with negative darkfield examinations and initial nonreactive serologic tests for syphilis, should be followed in two to four weeks by a repeat serologic test for syphilis.", "contents": "Simultaneous infection with Treponema pallidum and herpes simplex virus. Two cases are presented of simultaneous infection with Treponema pallidum and herpes simplex virus. The occasional concurrence of these diseases suggests that all cases of herpes genitalis, including those with negative darkfield examinations and initial nonreactive serologic tests for syphilis, should be followed in two to four weeks by a repeat serologic test for syphilis."}
{"id": "PMID:225131", "title": "Aniridia-Wilms' tumor association: evidence for specific deletion of 11p13.", "content": "A 7-year-old boy with aniridia, Wilms' tumor, and mental retardation, previously reported as having an interstitial deletion of the short arm of chromosome 8 resulting from a t(8p+;11q-) translocation (Ladda et al., 1974), has been restudied using high-resolution trypsin-Giemsa banding of prometaphase chromsomes. The results revealed a complex rearrangement with four break points in 8p, 11p, and 11q, leading to a net loss of an interstitial segment of 11p (region p1407 yields p1304) but not of 8p. His red blood cells contained normal activities of glutathione reductase (gene on 8p) and lactate dehydrogeanse A (gene on 11p12), indicating a gene dosage consistent with the chromosomal findings. The revised interpretation of this case agrees with seven others reported as having aniridia and interstitial 11p deletions in establishing the distal half of band 11p13 as the site of gene(s) which lead to aniridia and predispose to Wilms' tumor if present in a hemizygous state. Possible relationships between heterozygous deletion of specific chromosomal bands 11p13 and 13q14 and the autosomal dominant disorders aniridia, Wilms' tumor, and retinoblastoma, respectively, are discussed.", "contents": "Aniridia-Wilms' tumor association: evidence for specific deletion of 11p13. A 7-year-old boy with aniridia, Wilms' tumor, and mental retardation, previously reported as having an interstitial deletion of the short arm of chromosome 8 resulting from a t(8p+;11q-) translocation (Ladda et al., 1974), has been restudied using high-resolution trypsin-Giemsa banding of prometaphase chromsomes. The results revealed a complex rearrangement with four break points in 8p, 11p, and 11q, leading to a net loss of an interstitial segment of 11p (region p1407 yields p1304) but not of 8p. His red blood cells contained normal activities of glutathione reductase (gene on 8p) and lactate dehydrogeanse A (gene on 11p12), indicating a gene dosage consistent with the chromosomal findings. The revised interpretation of this case agrees with seven others reported as having aniridia and interstitial 11p deletions in establishing the distal half of band 11p13 as the site of gene(s) which lead to aniridia and predispose to Wilms' tumor if present in a hemizygous state. Possible relationships between heterozygous deletion of specific chromosomal bands 11p13 and 13q14 and the autosomal dominant disorders aniridia, Wilms' tumor, and retinoblastoma, respectively, are discussed."}
{"id": "PMID:225132", "title": "Clinical significance of pulmonary function tests. Alterations in pulmonary function following respiratory viral infection.", "content": "Respiratory viral illness is a major cause of morbidity in both adults and children. This report focuses on both the acute and chronic effects on respiratory function of these ubiquitous infections. Infant airways are particularly vulnerable due to the relatively low conductance in immature peripheral airways. Bronchiolitis, caused predominantly by respiratory syncytial virus, is the most important of these viral illnesses and is emerging as a major risk factor for the subsequent development of obstructive airway diseases in adults, possibly by interference with normal alveolar proliferation. The basic pathogenic mechanism involved in adult respiratory viral infection is bronchial hyperreactivity, presumably secondary to epithelial damage and resultant sensitization of rapidly adapting airway receptors. In addition, there may be virus-related alterations in the autonomic and humoral regulation of airway tone. Viral infections may alter the effects of common air pollutants on respiratory function.", "contents": "Clinical significance of pulmonary function tests. Alterations in pulmonary function following respiratory viral infection. Respiratory viral illness is a major cause of morbidity in both adults and children. This report focuses on both the acute and chronic effects on respiratory function of these ubiquitous infections. Infant airways are particularly vulnerable due to the relatively low conductance in immature peripheral airways. Bronchiolitis, caused predominantly by respiratory syncytial virus, is the most important of these viral illnesses and is emerging as a major risk factor for the subsequent development of obstructive airway diseases in adults, possibly by interference with normal alveolar proliferation. The basic pathogenic mechanism involved in adult respiratory viral infection is bronchial hyperreactivity, presumably secondary to epithelial damage and resultant sensitization of rapidly adapting airway receptors. In addition, there may be virus-related alterations in the autonomic and humoral regulation of airway tone. Viral infections may alter the effects of common air pollutants on respiratory function."}
{"id": "PMID:225133", "title": "Bronchial angiofibromata in a suspected case of tuberous sclerosis.", "content": "Widespread hamartomatous proliferations are often seen with tuberous sclerosis, yet pulmonary involvement is rare. We describe a patient with a probable forme fruste of tuberous sclerosis in whom the diagnosis of bronchial angiofibromata was made bronchoscopically. This is the first description of this pulmonary manifestation.", "contents": "Bronchial angiofibromata in a suspected case of tuberous sclerosis. Widespread hamartomatous proliferations are often seen with tuberous sclerosis, yet pulmonary involvement is rare. We describe a patient with a probable forme fruste of tuberous sclerosis in whom the diagnosis of bronchial angiofibromata was made bronchoscopically. This is the first description of this pulmonary manifestation."}
{"id": "PMID:225134", "title": "Attempts to standardize the screening for antiviral drugs by in vitro tests.", "content": "Plaque reduction (PR) and persistent infection cell culture (PICC) tests were used as a standard procedure for the selection of effective and well-tolerated antiviral compounds. Antiviral activity and cytotoxicity as well as other characteristics of the test compound, i.e., the development of drug resistance or the potential for activating the multiplication of other viruses can be examined by this method. In the described system analogues of 2'-deoxyuridine were tested against herpes simplex virus.", "contents": "Attempts to standardize the screening for antiviral drugs by in vitro tests. Plaque reduction (PR) and persistent infection cell culture (PICC) tests were used as a standard procedure for the selection of effective and well-tolerated antiviral compounds. Antiviral activity and cytotoxicity as well as other characteristics of the test compound, i.e., the development of drug resistance or the potential for activating the multiplication of other viruses can be examined by this method. In the described system analogues of 2'-deoxyuridine were tested against herpes simplex virus."}
{"id": "PMID:225135", "title": "9-(2-hydroxyethoxymethyl)guanine as an inhibitor of herpes simplex virus replication.", "content": "The drug 9-(2-hydroxyethoxymethyl)guanine effectively inhibits herpes simplex virus replication. It is selectively phosphorylated by the virus-induced thymidine kinase but not by normal cellular thymidine kinase.", "contents": "9-(2-hydroxyethoxymethyl)guanine as an inhibitor of herpes simplex virus replication. The drug 9-(2-hydroxyethoxymethyl)guanine effectively inhibits herpes simplex virus replication. It is selectively phosphorylated by the virus-induced thymidine kinase but not by normal cellular thymidine kinase."}
{"id": "PMID:225136", "title": "Therapeutic activity of pretazettine, a narcissus alkaloid, on spontaneous AKR leukemia.", "content": "A narcissus alkaloid, pretazettine hydrochloride (PTZ) has been shown to be active against spontaneous AKR leukemia. The long-term treatment with PTZ begining at 5--7 months of age of a group of AKR mice containing 10--20% of advanced leukemic mice significantly prolonged the life span of the group. The therapeutic effectiveness of PTZ has been compared with several standard antileukemic drugs. PTZ decreased the AKR virus titer in the circulating blood of mice and its antiviral activity in AKR virus infected NIH/3T3 cells has been confirmed by XC assay.", "contents": "Therapeutic activity of pretazettine, a narcissus alkaloid, on spontaneous AKR leukemia. A narcissus alkaloid, pretazettine hydrochloride (PTZ) has been shown to be active against spontaneous AKR leukemia. The long-term treatment with PTZ begining at 5--7 months of age of a group of AKR mice containing 10--20% of advanced leukemic mice significantly prolonged the life span of the group. The therapeutic effectiveness of PTZ has been compared with several standard antileukemic drugs. PTZ decreased the AKR virus titer in the circulating blood of mice and its antiviral activity in AKR virus infected NIH/3T3 cells has been confirmed by XC assay."}
{"id": "PMID:225137", "title": "[New aspects in the concept of adjuvant and after-care therapy for gastric carcinoma?].", "content": "Basis and current possibilities of adjuvant therapy in gastric cancer are discussed. The response rate with 5-FU und nitrosoureas for advanced gastric cancer is significantly superior to all other regimens. Based on Japanese experiences a higher survival rate is observed in the curatively resected patients treated with postoperative prophylactic chemotherapy. The drawing of reliable conclusions must await the results of further studies. Efforts for individual chemotherapy by measurement of cell production of recurrences and the necessity of aftercare in gastric cancer patients are explained.", "contents": "[New aspects in the concept of adjuvant and after-care therapy for gastric carcinoma?]. Basis and current possibilities of adjuvant therapy in gastric cancer are discussed. The response rate with 5-FU und nitrosoureas for advanced gastric cancer is significantly superior to all other regimens. Based on Japanese experiences a higher survival rate is observed in the curatively resected patients treated with postoperative prophylactic chemotherapy. The drawing of reliable conclusions must await the results of further studies. Efforts for individual chemotherapy by measurement of cell production of recurrences and the necessity of aftercare in gastric cancer patients are explained."}
{"id": "PMID:225139", "title": "Dioxygen and the vitamin K-dependent synthesis of prothrombin.", "content": "It has been shown that bovine erythrocyte superoxide dismutase inhibits the gamma-carboxylation of glutamyl residues in the precursor of prothrombin and in a related synthetic peptide by a vitamin K-dependent rat liver microsomal carboxylase. In the same conditions a simple copper(II) tyrosinyl complex also inhibits the carobxylation. The formation of the vitamin K epoxide by the same systems is inhibited by both superoxide dismutase and catalase. It is suggested that the formation of the epoxide is a process distinct from carboxylation, representing perhaps a protective mechanism against the superoxide ion, or species derived therefrom, generated by the reaction of reduced vitamin K with dioxygen. Furthermore, the possibility that the carboxylating species is formed by the reaction of the superoxide ion, or species derived therefrom, with carbon dioxide, is proposed.", "contents": "Dioxygen and the vitamin K-dependent synthesis of prothrombin. It has been shown that bovine erythrocyte superoxide dismutase inhibits the gamma-carboxylation of glutamyl residues in the precursor of prothrombin and in a related synthetic peptide by a vitamin K-dependent rat liver microsomal carboxylase. In the same conditions a simple copper(II) tyrosinyl complex also inhibits the carobxylation. The formation of the vitamin K epoxide by the same systems is inhibited by both superoxide dismutase and catalase. It is suggested that the formation of the epoxide is a process distinct from carboxylation, representing perhaps a protective mechanism against the superoxide ion, or species derived therefrom, generated by the reaction of reduced vitamin K with dioxygen. Furthermore, the possibility that the carboxylating species is formed by the reaction of the superoxide ion, or species derived therefrom, with carbon dioxide, is proposed."}
{"id": "PMID:225140", "title": "Oxygen consumption by stimulated human neutrophils.", "content": "Oxygen consumption by stimulated human neutrophils has been studied. An initial lag after stimulation of about 20 s is followed by a linear phase of oxygen consumption which lasts about 60 s and then declines exponentially. The duration of the respiratory  burst is thus much shorter than has been generally recognized. The cessation of the linear phase of oxygen consumption occurs at a constant time after stimulation, is not due to depletion of the substrate of the oxidase enzyme (since linear oxygen consumption can be re-initiated), and is due to termination or saturation of particle uptake. The curtailment of oxygen consumption probably marks the end of the oxygen-dependent microbial role of the phagocytic vacuole, preparing it for the secondary and independent function of digestion. A novel cytochrome b becomes associated with the phagosomes and probably forms a component of a complex electron-transport chain. Superoxide may be an intermediate in this system, but it is unlikely to be released free from the cell or to form the final product of the system.", "contents": "Oxygen consumption by stimulated human neutrophils. Oxygen consumption by stimulated human neutrophils has been studied. An initial lag after stimulation of about 20 s is followed by a linear phase of oxygen consumption which lasts about 60 s and then declines exponentially. The duration of the respiratory  burst is thus much shorter than has been generally recognized. The cessation of the linear phase of oxygen consumption occurs at a constant time after stimulation, is not due to depletion of the substrate of the oxidase enzyme (since linear oxygen consumption can be re-initiated), and is due to termination or saturation of particle uptake. The curtailment of oxygen consumption probably marks the end of the oxygen-dependent microbial role of the phagocytic vacuole, preparing it for the secondary and independent function of digestion. A novel cytochrome b becomes associated with the phagosomes and probably forms a component of a complex electron-transport chain. Superoxide may be an intermediate in this system, but it is unlikely to be released free from the cell or to form the final product of the system."}
{"id": "PMID:225141", "title": "Defects in the oxidative killing of microorganisms by phagocytic leukocytes.", "content": "One of the most important mechanisms of phagocytic killing of ingested microorganisms by leukocytes is the generation of toxic oxygen products. During phagocytosis, neutrophils, as well as monocytes and macrophages, display a strongly increased cell respiration. Quantitatively the most important product of this reaction is hydrogen peroxide. Superoxide is also generated in large amounts, probably as an intermediate in the formation of hydrogen peroxide. Indications exist that singlet oxygen and hydroxyl radicals are also formed in this process. Some of these oxygen products have microbicidal properties by themselves. The effect of hydrogen peroxide is greatly enhanced by the enzyme myeloperoxidase. Several dysfunctions of this sytem are known. In chronic granulomatous disease the enzyme system that produces superoxide is not operative. Thus, no superoxide or hydrogen peroxide is generated, leading to a severely decreased bacterial killing capacity. The exact molecular defects in the X-linked and the autosomal form are as yet undefined. Two variants are also known: lipochrome histiocytosis, with different clinical and histological manifestations, and a 'triggering defect' where only strongly opsonized particles trigger the respiratory burst. Myeloperoxidase deficiency leads to slightly decreased killing capacity, especially for yeasts. In glucose-6-phosphate dehydrogenase deficiency no oxygen radicals or hydrogen peroxide are produced because no equivalents for oxygen reduction can be generated in the hexose-monophosphate shunt. Deficiencies in the glutathione redox system also result in impaired phagocyte function, probably because the cells have to be protected against their own toxic oxygen products.", "contents": "Defects in the oxidative killing of microorganisms by phagocytic leukocytes. One of the most important mechanisms of phagocytic killing of ingested microorganisms by leukocytes is the generation of toxic oxygen products. During phagocytosis, neutrophils, as well as monocytes and macrophages, display a strongly increased cell respiration. Quantitatively the most important product of this reaction is hydrogen peroxide. Superoxide is also generated in large amounts, probably as an intermediate in the formation of hydrogen peroxide. Indications exist that singlet oxygen and hydroxyl radicals are also formed in this process. Some of these oxygen products have microbicidal properties by themselves. The effect of hydrogen peroxide is greatly enhanced by the enzyme myeloperoxidase. Several dysfunctions of this sytem are known. In chronic granulomatous disease the enzyme system that produces superoxide is not operative. Thus, no superoxide or hydrogen peroxide is generated, leading to a severely decreased bacterial killing capacity. The exact molecular defects in the X-linked and the autosomal form are as yet undefined. Two variants are also known: lipochrome histiocytosis, with different clinical and histological manifestations, and a 'triggering defect' where only strongly opsonized particles trigger the respiratory burst. Myeloperoxidase deficiency leads to slightly decreased killing capacity, especially for yeasts. In glucose-6-phosphate dehydrogenase deficiency no oxygen radicals or hydrogen peroxide are produced because no equivalents for oxygen reduction can be generated in the hexose-monophosphate shunt. Deficiencies in the glutathione redox system also result in impaired phagocyte function, probably because the cells have to be protected against their own toxic oxygen products."}
{"id": "PMID:225142", "title": "The role of myeloperoxidase in the microbicidal activity of polymorphonuclear leukocytes.", "content": "Myeloperoxidase (MPO), H2O2 and a halide form a powerful antimicrobial system effective against bacteria, fungi, viruses and mammalian cells. After phagocytosis, MPO is released into the phagosome from adjacent granules where it interacts with H2O2 generated either by leukocytic or microbial metabolism and a halide such as chloride or iodide to form agents toxic to the ingested organisms. Evidence for H2O2 and MPO participation in the microbicidal activity of polymorphonuclear leukocytes (PMNs) has been obtained from patients with neutrophil dysfunction. In chronic granulomatous disease, PMNs have a microbicidal defect associated with the absence of the respiratory burst. The importance of H2O2 deficiency in the PMN dysfunction is emphasized by its reversal by H2O2. PMNs which lack MPO also have a major fungicidal and bactericidal defect. Bactericidal activity is particularly low during the early postphagocytic period, after which the organisms are killed. Although emphasizing the importance of MPO-mediated antimicrobial systems particularly during the early postphagocytic period, these findings also indicate the presence of MPO-independent systems which develop slowly but are ultimately effective. The MPO-independent antimicrobial systems may be oxygen-dependent or oxygen-independent. The acetaldehyde-xanthine oxidase system has been used as a model of the MPO-independent, oxygen-dependent antimicrobial systems of the PMN. A microbicidal effect by this system was observed which was inhibited by superoxide dismutase, catalase and scavengers of hydroxyl radicals (OH') and singlet oxygen (1O2). The microbicidal activity of acetaldehyde and xanthine oxidase is increased considerably by MPO and chloride. The formation of ethylene from methional or 2-oxo-4-methylthiobutyric acid by PMNs has been regarded as evidence for OH' formation. We have found ethylene formation to be largely dependent on MPO and evidence for the initiation of ethylene formation by 1O2 has been obtained. Both the xanthine oxidase system and the MPO-H2O2-halide system convert diphenylfuran into cis-dibenzoylethylene, an effect which is compatible with, although not proof of, the formation of 1O2 by these systems.", "contents": "The role of myeloperoxidase in the microbicidal activity of polymorphonuclear leukocytes. Myeloperoxidase (MPO), H2O2 and a halide form a powerful antimicrobial system effective against bacteria, fungi, viruses and mammalian cells. After phagocytosis, MPO is released into the phagosome from adjacent granules where it interacts with H2O2 generated either by leukocytic or microbial metabolism and a halide such as chloride or iodide to form agents toxic to the ingested organisms. Evidence for H2O2 and MPO participation in the microbicidal activity of polymorphonuclear leukocytes (PMNs) has been obtained from patients with neutrophil dysfunction. In chronic granulomatous disease, PMNs have a microbicidal defect associated with the absence of the respiratory burst. The importance of H2O2 deficiency in the PMN dysfunction is emphasized by its reversal by H2O2. PMNs which lack MPO also have a major fungicidal and bactericidal defect. Bactericidal activity is particularly low during the early postphagocytic period, after which the organisms are killed. Although emphasizing the importance of MPO-mediated antimicrobial systems particularly during the early postphagocytic period, these findings also indicate the presence of MPO-independent systems which develop slowly but are ultimately effective. The MPO-independent antimicrobial systems may be oxygen-dependent or oxygen-independent. The acetaldehyde-xanthine oxidase system has been used as a model of the MPO-independent, oxygen-dependent antimicrobial systems of the PMN. A microbicidal effect by this system was observed which was inhibited by superoxide dismutase, catalase and scavengers of hydroxyl radicals (OH') and singlet oxygen (1O2). The microbicidal activity of acetaldehyde and xanthine oxidase is increased considerably by MPO and chloride. The formation of ethylene from methional or 2-oxo-4-methylthiobutyric acid by PMNs has been regarded as evidence for OH' formation. We have found ethylene formation to be largely dependent on MPO and evidence for the initiation of ethylene formation by 1O2 has been obtained. Both the xanthine oxidase system and the MPO-H2O2-halide system convert diphenylfuran into cis-dibenzoylethylene, an effect which is compatible with, although not proof of, the formation of 1O2 by these systems."}
{"id": "PMID:225143", "title": "The lactoperoxidase-thiocyanate-hydrogen peroxide antibacterium system.", "content": "Lactoperoxidase present in various secretions oxidizes thiocyanate (SCN-) in the presence of H2O2 to an unstable oxidation product--hypothiocyanite (OSCN-), which is bactericidal for enteric pathogens including multiple antibiotic resistant strains of E. coli. The system damages the inner membrane causing leakage and cessation of uptake of nutrient, leading eventually to death of the organisms and lysis. The possible involvement of O2- and 1O2 is discussed.", "contents": "The lactoperoxidase-thiocyanate-hydrogen peroxide antibacterium system. Lactoperoxidase present in various secretions oxidizes thiocyanate (SCN-) in the presence of H2O2 to an unstable oxidation product--hypothiocyanite (OSCN-), which is bactericidal for enteric pathogens including multiple antibiotic resistant strains of E. coli. The system damages the inner membrane causing leakage and cessation of uptake of nutrient, leading eventually to death of the organisms and lysis. The possible involvement of O2- and 1O2 is discussed."}
{"id": "PMID:225144", "title": "Phagocyte-produced free radicals: roles in cytotoxicity and inflammation.", "content": "The production of superoxide free radical, O2-, by metabolically activated phagocytes results in damage to the phagocyte which is manifested by the premature death of the cell in vitro. The cytotoxic agent appears to be formed by the reaction of superoxide with hydrogen peroxide, and is thought to be hydroxyl radical or a secondary radical thereof. In vivo two animal models of induced inflammation also appear to be largely dependent on superoxide production by phagocytes for the development of tissue damage manifested as oedema. Intravenously administered superoxide dismutase shows anti-inflammatory activity in these models, but only when so derivatized that it can remain in the circulation for longer periods of time. Catalase, or a catalase derivative, on the other hand, shows no anti-inflammatory activity in vivo.", "contents": "Phagocyte-produced free radicals: roles in cytotoxicity and inflammation. The production of superoxide free radical, O2-, by metabolically activated phagocytes results in damage to the phagocyte which is manifested by the premature death of the cell in vitro. The cytotoxic agent appears to be formed by the reaction of superoxide with hydrogen peroxide, and is thought to be hydroxyl radical or a secondary radical thereof. In vivo two animal models of induced inflammation also appear to be largely dependent on superoxide production by phagocytes for the development of tissue damage manifested as oedema. Intravenously administered superoxide dismutase shows anti-inflammatory activity in these models, but only when so derivatized that it can remain in the circulation for longer periods of time. Catalase, or a catalase derivative, on the other hand, shows no anti-inflammatory activity in vivo."}
{"id": "PMID:225146", "title": "The chemistry of dioxygen and its reduction products.", "content": "The electronic properties of dioxygen are discussed with reference to its reactions in biological systems. In particular, the importance of its reduction to the superoxide ion is stressed. The physical and chemical properties of the superoxide ion are described and their relevance to its function in biochemical processes is emphasized. The relationship to other intermediates such as the hydroxyl radical is discussed.", "contents": "The chemistry of dioxygen and its reduction products. The electronic properties of dioxygen are discussed with reference to its reactions in biological systems. In particular, the importance of its reduction to the superoxide ion is stressed. The physical and chemical properties of the superoxide ion are described and their relevance to its function in biochemical processes is emphasized. The relationship to other intermediates such as the hydroxyl radical is discussed."}
{"id": "PMID:225147", "title": "Superoxide dismutases: defence against endogenous superoxide radical.", "content": "Attempts to measure the rate of O2- production, in whole cells or in intact subcellular organelles, are frustrated by the endogenous superoxide dismutase (SOD). Streptococcus faecalis contains a single manganese-SOD which was isolated and used as an antigen in the rabbit. A precipitating and inhibiting antibody was obtained and used to suppress the SOD in crude lysates of S. faecalis. It allowed the demonstration that 17% of the total oxygen uptake by such lysates, in the presence of NADH, was associated with O2- production. O2- attacks unsaturated lipids and breaches the integrity of membranes. When the membranes are free of lipid hydroperoxides, then both O2- and H2O2 are required and singlet oxygen appears to be the proximal attacking species. When the membrane contains some lipid hydroperoxide, then O2- is itself sufficient and seems to generate an alkoxy radical, by reacting with the lipid hydroperoxide. It appears likely that attack on membranes is one of the reasons for the cytotoxicity of O2-. In Escherichia coli the manganese-SOD is derepressed by O2-. This enzyme is not made in the absence of oxygen and in aerobic conditions any change which results in enhanced production of O2- calls forth an increased synthesis of this enzyme. Increased levels of SOD, however achieved, correlate with greater resistance towards oxygen toxicity. It is generally true that respiring cells contain more SOD than non-respiring cells. Among obligate anaerobes there is a correlation between SOD-content and tolerance towards oxygen. It is not known whether the SOD in obligate anaerobes is a retained primitive characteristic or one recently acquired by plasmid transfer. There is an exception to the rule that copper-zinc-SOD is found in eukaryotes but not in prokaryotes, and that is the symbiotic bacterium Photobacterium leiognathi. This symbiont may have obtained the Cu-ZnSOD gene from the host fish.", "contents": "Superoxide dismutases: defence against endogenous superoxide radical. Attempts to measure the rate of O2- production, in whole cells or in intact subcellular organelles, are frustrated by the endogenous superoxide dismutase (SOD). Streptococcus faecalis contains a single manganese-SOD which was isolated and used as an antigen in the rabbit. A precipitating and inhibiting antibody was obtained and used to suppress the SOD in crude lysates of S. faecalis. It allowed the demonstration that 17% of the total oxygen uptake by such lysates, in the presence of NADH, was associated with O2- production. O2- attacks unsaturated lipids and breaches the integrity of membranes. When the membranes are free of lipid hydroperoxides, then both O2- and H2O2 are required and singlet oxygen appears to be the proximal attacking species. When the membrane contains some lipid hydroperoxide, then O2- is itself sufficient and seems to generate an alkoxy radical, by reacting with the lipid hydroperoxide. It appears likely that attack on membranes is one of the reasons for the cytotoxicity of O2-. In Escherichia coli the manganese-SOD is derepressed by O2-. This enzyme is not made in the absence of oxygen and in aerobic conditions any change which results in enhanced production of O2- calls forth an increased synthesis of this enzyme. Increased levels of SOD, however achieved, correlate with greater resistance towards oxygen toxicity. It is generally true that respiring cells contain more SOD than non-respiring cells. Among obligate anaerobes there is a correlation between SOD-content and tolerance towards oxygen. It is not known whether the SOD in obligate anaerobes is a retained primitive characteristic or one recently acquired by plasmid transfer. There is an exception to the rule that copper-zinc-SOD is found in eukaryotes but not in prokaryotes, and that is the symbiotic bacterium Photobacterium leiognathi. This symbiont may have obtained the Cu-ZnSOD gene from the host fish."}
{"id": "PMID:225148", "title": "The role of viral transformation and cytogenetic changes in viral oncogenesis.", "content": "A wide variety of DNA viruses and a more restricted family of RNA viruses can transform normal cells in vitro. Transformation means either immortalization and/or the appearance of certain phenotypic changes. Although it has been often inferred that in vitro transformation can be essentially equated with malignant transformation, increasing evidence indicates that the latter, reflected by tumorigenicity in vivo, requires additional cytogenetic changes. The evidence will be reviewed for EB virus-associated human malignancy (Burkitt's lymphoma) and the role of the 14q + translocation marker in human B-cell neoplasia. These findings point to an initiating role of viral transformation, reflected by in vitro immortalization, followed by a cytogenetic evolution where chromosome 14-associated changes are essential for the liberation of B lymphocytes from super-imposed controls. The contrast of tissue-associated, specific chromosomal changes that bring about malignant transformation after the initiating impact of different agents will be illustrated experimentally for murine T-cell lymphoma. Here, X-ray, DMBA and different virus (RadLV, Gross virus)-induced T lymphomas show the same chromosomal change: trisomy 15. It may be questioned whether viral transformation can ever lead to neoplasia in the absence of subsequent cytogenetic changes.", "contents": "The role of viral transformation and cytogenetic changes in viral oncogenesis. A wide variety of DNA viruses and a more restricted family of RNA viruses can transform normal cells in vitro. Transformation means either immortalization and/or the appearance of certain phenotypic changes. Although it has been often inferred that in vitro transformation can be essentially equated with malignant transformation, increasing evidence indicates that the latter, reflected by tumorigenicity in vivo, requires additional cytogenetic changes. The evidence will be reviewed for EB virus-associated human malignancy (Burkitt's lymphoma) and the role of the 14q + translocation marker in human B-cell neoplasia. These findings point to an initiating role of viral transformation, reflected by in vitro immortalization, followed by a cytogenetic evolution where chromosome 14-associated changes are essential for the liberation of B lymphocytes from super-imposed controls. The contrast of tissue-associated, specific chromosomal changes that bring about malignant transformation after the initiating impact of different agents will be illustrated experimentally for murine T-cell lymphoma. Here, X-ray, DMBA and different virus (RadLV, Gross virus)-induced T lymphomas show the same chromosomal change: trisomy 15. It may be questioned whether viral transformation can ever lead to neoplasia in the absence of subsequent cytogenetic changes."}
{"id": "PMID:225154", "title": "[Therapeutic and diagnostic problems of generalized acute suppurative periodontitis marginalis profunda].", "content": "Generalized periodontal abscesses with considerable increase in the volume and sensitivity of the gingiva, tooth loosening, and malaise accompanied by fever and weight loss were observed in 22 of 35 patients studied. The symptoms developed after antibiotic treatment for another disease. Local therapeutic measures alone were successful. Success was obtained only after institution of directed antibiotic therapy.", "contents": "[Therapeutic and diagnostic problems of generalized acute suppurative periodontitis marginalis profunda]. Generalized periodontal abscesses with considerable increase in the volume and sensitivity of the gingiva, tooth loosening, and malaise accompanied by fever and weight loss were observed in 22 of 35 patients studied. The symptoms developed after antibiotic treatment for another disease. Local therapeutic measures alone were successful. Success was obtained only after institution of directed antibiotic therapy."}
{"id": "PMID:225155", "title": "[Reversible alterations of peripheral nerve function in thyroid dysfunction (author's transl)].", "content": "In 7 patients with hyperthyroidism and 9 patients with hypothyroidism both thve before treatment and after a period of normal thyroid function of at least one year duration. As far as conduction velocity and relative refractory period are concerned there was no difference between hyperthyroid patients and normal persons, whereas in cases of hypothyroidism before treatment the conduction velocity was shown to be significantly reduced; moreover a prolonged relative refractory period and a decline in amplitude of the nerve action potential were found. These alterations of peripheral nerve function, interpreted as evidence of neuropathy, proved to be reversible when the thyroid function returned to normal.", "contents": "[Reversible alterations of peripheral nerve function in thyroid dysfunction (author's transl)]. In 7 patients with hyperthyroidism and 9 patients with hypothyroidism both thve before treatment and after a period of normal thyroid function of at least one year duration. As far as conduction velocity and relative refractory period are concerned there was no difference between hyperthyroid patients and normal persons, whereas in cases of hypothyroidism before treatment the conduction velocity was shown to be significantly reduced; moreover a prolonged relative refractory period and a decline in amplitude of the nerve action potential were found. These alterations of peripheral nerve function, interpreted as evidence of neuropathy, proved to be reversible when the thyroid function returned to normal."}
{"id": "PMID:225156", "title": "[Electroencephalographic assessment of dosage and sleep-profile in a hypnotic Triazolothienodiazepine (author's transl)].", "content": "We 941, a Triazolodiazepine, has satisfying hypnotic properties. The optimum dosage lies nearly at 0.3 mg. In this dosage the sleep-begin is shortened, the number of nightly wakeness is decreased and the total sleep-time is extended, while the sleep-profile remains unchanged. A normal cycling can be taken as a sign of qualitative good sleep. The REM-percentage is diminished insignificantly and increases again under the continuated therapy. The percentage of deep sleep increases by 0.3 mg. The subjective presentations confirm the melioration of sleep. In higher dosages troubles occur as decrease of deep-sleep stage and deteriorations of feeling. Remarkable is the withdrawal effect after 1.0 mg with an initial and a dissociated REM. However, such strong disturbances couldn't be observed in the carried on therapy with 0.3 mg.", "contents": "[Electroencephalographic assessment of dosage and sleep-profile in a hypnotic Triazolothienodiazepine (author's transl)]. We 941, a Triazolodiazepine, has satisfying hypnotic properties. The optimum dosage lies nearly at 0.3 mg. In this dosage the sleep-begin is shortened, the number of nightly wakeness is decreased and the total sleep-time is extended, while the sleep-profile remains unchanged. A normal cycling can be taken as a sign of qualitative good sleep. The REM-percentage is diminished insignificantly and increases again under the continuated therapy. The percentage of deep sleep increases by 0.3 mg. The subjective presentations confirm the melioration of sleep. In higher dosages troubles occur as decrease of deep-sleep stage and deteriorations of feeling. Remarkable is the withdrawal effect after 1.0 mg with an initial and a dissociated REM. However, such strong disturbances couldn't be observed in the carried on therapy with 0.3 mg."}
{"id": "PMID:225158", "title": "Stimulation of guanosine 3',5'-monophosphate-phosphodiesterase activity by adrenocorticotropic hormone-activated increase of guanosine 3',5'-monophosphate in isolated adrenocortical carcinoma cells.", "content": "The decline of the ACTH-stimulated cGMP to the basal level in isolated adrenocortical carcinoma cells was inhibited by cyclic phosphodiesterase inhibitors. Time-course experiments showed that the ACTH-induced level of cGMP preceded the activation of phosphodiesterase. Cells incubated with increasing concentrations of exogenous cGMP responded with a corresponding increase in the cGMP-phosphodiesterase activity. cAMP was 100-fold less effective than cGMP in the activation of cGMP-phosphodiesterase, indicating the nucleotide specificity of enzyme activation. The activation of cGMP-phosphodiesterase by ACTH-induced cGMP or exogenous cGMP was rapid. In contrast to these observations, there was no activation of cAMP-phosphodiesterase by exogenous cAMP or cGMP. These results indicate that one mechanism by which isolated adrenocortical carcinoma cells regulate the ACTH-induced increase in cGMP is the cyclic nucleotide control of the activity of its phosphodiesterase, thereby regulating cGMP degradation.", "contents": "Stimulation of guanosine 3',5'-monophosphate-phosphodiesterase activity by adrenocorticotropic hormone-activated increase of guanosine 3',5'-monophosphate in isolated adrenocortical carcinoma cells. The decline of the ACTH-stimulated cGMP to the basal level in isolated adrenocortical carcinoma cells was inhibited by cyclic phosphodiesterase inhibitors. Time-course experiments showed that the ACTH-induced level of cGMP preceded the activation of phosphodiesterase. Cells incubated with increasing concentrations of exogenous cGMP responded with a corresponding increase in the cGMP-phosphodiesterase activity. cAMP was 100-fold less effective than cGMP in the activation of cGMP-phosphodiesterase, indicating the nucleotide specificity of enzyme activation. The activation of cGMP-phosphodiesterase by ACTH-induced cGMP or exogenous cGMP was rapid. In contrast to these observations, there was no activation of cAMP-phosphodiesterase by exogenous cAMP or cGMP. These results indicate that one mechanism by which isolated adrenocortical carcinoma cells regulate the ACTH-induced increase in cGMP is the cyclic nucleotide control of the activity of its phosphodiesterase, thereby regulating cGMP degradation."}
{"id": "PMID:225159", "title": "Acute self-suppression of corticosteroidogenesis in isolated adrenocortical cells.", "content": "The relation between steroidogenesis induced by ACTH and that induced by exogenous concentrations of glucocorticoids was studied in isolated adrenocortical cells. Exogenous corticosterone and cortisol, in concentrations within the production capacity of the adrenal gland, suppressed steroidogenesis induced by ACTH in rat and beef cells, respectively. The precursors pregnenolone and progesterone enhanced steroidogenesis in both rat and beef cells. Aldosterone in rat cells and 17 beta-estradiol in rat and beef cells had little if any effect on steroidogenesis. Either suppression or stimulation by exogenous steroids was acute, that is, after 2-h incubation for rat cells and 1-h incubation for beef cells. A direct suppressive action of end product glucocorticoids is indicated. This observed self-suppression of adrenocortical cells suggests the existence of a mechanism for the find adjustment of steroidogenesis that operates in addition to the classical control exerted by the anterior pituitary.", "contents": "Acute self-suppression of corticosteroidogenesis in isolated adrenocortical cells. The relation between steroidogenesis induced by ACTH and that induced by exogenous concentrations of glucocorticoids was studied in isolated adrenocortical cells. Exogenous corticosterone and cortisol, in concentrations within the production capacity of the adrenal gland, suppressed steroidogenesis induced by ACTH in rat and beef cells, respectively. The precursors pregnenolone and progesterone enhanced steroidogenesis in both rat and beef cells. Aldosterone in rat cells and 17 beta-estradiol in rat and beef cells had little if any effect on steroidogenesis. Either suppression or stimulation by exogenous steroids was acute, that is, after 2-h incubation for rat cells and 1-h incubation for beef cells. A direct suppressive action of end product glucocorticoids is indicated. This observed self-suppression of adrenocortical cells suggests the existence of a mechanism for the find adjustment of steroidogenesis that operates in addition to the classical control exerted by the anterior pituitary."}
{"id": "PMID:225161", "title": "Effect of calcium administration on renal responsiveness to parathyroid hormone in pseudohypoparathyroidism type I and II -- in comparison with normals, idiopathic and surgical hypoparathyroidism.", "content": "A 31-year-old man and a 12-year-old girl were diagnosed as pseudohypoparathyroidism (PHP) Type I because of a failure to respond to the administration of parathyroid hormone (PTH) with increased urinary excretion of phosphate and cyclic adenosine-3', 5'-monophosphate (cAMP). A 22-year-old woman was diagnosed as PHP Type II because there was no increase in the urinary excretion of phosphate despite of a marked increase in urinary cAMP excretion. With the combined calcium-PTH infusion or PTH infusion after vitamin D therapy, renal response was improved in these patients. Also dibutyryl adenosine-3'-5'-cyclic monophosphate (dbcAMP) infusion evoked an increased urinary phosphate excretion in all of the patients. The metabolic defect of our patients with PHP Type I may be caused not by a lack or defective form of PTH-sensitive receptor adenylate cyclase complex but rather by an abnormal conformation in the plasma membrane-associated receptor adenylate cyclase enzyme complex in kidney. In the patient with PHP Type II, as cAMP generation is intact, the metabolic defect might be related to a defect of calcium mobilization in renal tubular cells in response to PTH.", "contents": "Effect of calcium administration on renal responsiveness to parathyroid hormone in pseudohypoparathyroidism type I and II -- in comparison with normals, idiopathic and surgical hypoparathyroidism. A 31-year-old man and a 12-year-old girl were diagnosed as pseudohypoparathyroidism (PHP) Type I because of a failure to respond to the administration of parathyroid hormone (PTH) with increased urinary excretion of phosphate and cyclic adenosine-3', 5'-monophosphate (cAMP). A 22-year-old woman was diagnosed as PHP Type II because there was no increase in the urinary excretion of phosphate despite of a marked increase in urinary cAMP excretion. With the combined calcium-PTH infusion or PTH infusion after vitamin D therapy, renal response was improved in these patients. Also dibutyryl adenosine-3'-5'-cyclic monophosphate (dbcAMP) infusion evoked an increased urinary phosphate excretion in all of the patients. The metabolic defect of our patients with PHP Type I may be caused not by a lack or defective form of PTH-sensitive receptor adenylate cyclase complex but rather by an abnormal conformation in the plasma membrane-associated receptor adenylate cyclase enzyme complex in kidney. In the patient with PHP Type II, as cAMP generation is intact, the metabolic defect might be related to a defect of calcium mobilization in renal tubular cells in response to PTH."}
{"id": "PMID:225162", "title": "Effects of ACTH and calcium on cyclic AMP production and steroid output by the zona glomerulosa of the adrenal cortex.", "content": "Effects of ACTH and calcium on cyclic AMP production and steroid output by the zona glomerulosa (the capsular fraction) from the rat adrenal cortex have been studied. Although high concentrations of extracellular calcium potentiated the stimulatory action of ACTH on cyclic AMP and aldosterone output, tetracaine or verapamil inhibited aldosterone output but not cyclic AMP production during ACTH-stimulation. Lanthanum reduced both aldosterone and cyclic AMP accumulation induced by ACTH. These results suggest that an extracellular calcium would be essential in stimulating the capsular steroidogenesis without involvement of the cyclic AMP system.", "contents": "Effects of ACTH and calcium on cyclic AMP production and steroid output by the zona glomerulosa of the adrenal cortex. Effects of ACTH and calcium on cyclic AMP production and steroid output by the zona glomerulosa (the capsular fraction) from the rat adrenal cortex have been studied. Although high concentrations of extracellular calcium potentiated the stimulatory action of ACTH on cyclic AMP and aldosterone output, tetracaine or verapamil inhibited aldosterone output but not cyclic AMP production during ACTH-stimulation. Lanthanum reduced both aldosterone and cyclic AMP accumulation induced by ACTH. These results suggest that an extracellular calcium would be essential in stimulating the capsular steroidogenesis without involvement of the cyclic AMP system."}
{"id": "PMID:225163", "title": "Calcium ion as \"second messenger\" in corticoidogenic action of ACTH.", "content": "The correlation between corticoidogenesis and Ca2+-influx in the cell was investigated using isolated rat or bovine adrenocortical cells. 1) ACTH-induced corticoidogenesis in both rat and bovine adrenocortical cells was enhanced in parallel with increasing concentration of external Ca2+. In the bovine cells but not in the rat cells, moreover, the marked stimulatory effect of external Ca2+ on the corticoidogenesis was observed despite the absence of ACTH. 2) Ca2+-influx and corticoidogenesis always occurred unitedly. 3) Verapamil markedly inhibited either corticoidogenesis or Ca2+-influx in response to ACTH. 4) The stimulatory effect of Ca2+ on corticoidogenesis was completely blocked by cycloheximide. It was therefore suggested that Ca2+ could regulate corticoidogenesis as a primary \"second messenger\" of ACTH through biosynthesis of so-called steroidogenic protein.", "contents": "Calcium ion as \"second messenger\" in corticoidogenic action of ACTH. The correlation between corticoidogenesis and Ca2+-influx in the cell was investigated using isolated rat or bovine adrenocortical cells. 1) ACTH-induced corticoidogenesis in both rat and bovine adrenocortical cells was enhanced in parallel with increasing concentration of external Ca2+. In the bovine cells but not in the rat cells, moreover, the marked stimulatory effect of external Ca2+ on the corticoidogenesis was observed despite the absence of ACTH. 2) Ca2+-influx and corticoidogenesis always occurred unitedly. 3) Verapamil markedly inhibited either corticoidogenesis or Ca2+-influx in response to ACTH. 4) The stimulatory effect of Ca2+ on corticoidogenesis was completely blocked by cycloheximide. It was therefore suggested that Ca2+ could regulate corticoidogenesis as a primary \"second messenger\" of ACTH through biosynthesis of so-called steroidogenic protein."}
{"id": "PMID:225164", "title": "Effects of vasopressin and cyclic AMP on water transport at arachnoid villi of cats.", "content": "The effects of vasopressin and cyclic AMP on water transport at arachnoid villi into the superior sagittal sinus were examined using the isolated meninges preparations of cats. The meninges preparation, the superior sagittal sinus of which was opened at the midline of the outer surface, was held between two polyethylene tubes. The tubes were fixed vertically in the way that the opened surface of the sinus was directed downward and arachnoid surface upward. Water transport was determined by measuring the tritiated water dripping through the membrane preparation. Vasopressin from less than 50 to 500 muU/ml accelerated the water transport and this effect was dose-dependent. Cyclic AMP from 0.5 to 10 mM was proved to manifest the same effect as vasopressin. This effect of cyclic AMP appeared rapidly in comparison with that of vasopressin, suggesting that the effect of vasopressin may be manifested through cyclic AMP. From these findings a physiological role of vasopressin in cerebrospinal fluid was discussed regarding the regulation of intracranial pressure.", "contents": "Effects of vasopressin and cyclic AMP on water transport at arachnoid villi of cats. The effects of vasopressin and cyclic AMP on water transport at arachnoid villi into the superior sagittal sinus were examined using the isolated meninges preparations of cats. The meninges preparation, the superior sagittal sinus of which was opened at the midline of the outer surface, was held between two polyethylene tubes. The tubes were fixed vertically in the way that the opened surface of the sinus was directed downward and arachnoid surface upward. Water transport was determined by measuring the tritiated water dripping through the membrane preparation. Vasopressin from less than 50 to 500 muU/ml accelerated the water transport and this effect was dose-dependent. Cyclic AMP from 0.5 to 10 mM was proved to manifest the same effect as vasopressin. This effect of cyclic AMP appeared rapidly in comparison with that of vasopressin, suggesting that the effect of vasopressin may be manifested through cyclic AMP. From these findings a physiological role of vasopressin in cerebrospinal fluid was discussed regarding the regulation of intracranial pressure."}
{"id": "PMID:225166", "title": "Inactivation of human thyroid stimulator by human thyroid extract.", "content": "To determine whether the thyroid stimulating activity of IGG of patients with Graves' disease is associated with the reaction with a putative human thyroid antigen, the inactivation of the property of IgG to stimulate cAMP generation in human thyroid slices incubated in vitro was studied by pretreating the IgG with human thyroidal particulate fraction. In the preliminary experiment, it was demonstrated that to cause cAMP generation stimulation, on incubation period of 120 min is required to allow the IgG to penetrate the tissue. When human thyroid slices were incubated with normal IgG without or with pretreatment by human thyroid particulate fraction obtained from 100 mg tissue, cAMP content in the slices was 142 +/- 25 or 138 +/- 26 f moles/mg, respectively, indicating that basal thyroidal cAMP levels were not influenced at all by normal IgG even after pretreatment with thyroid particulate fraction. When the slices were incubated with gG of Graves' disease without or with the similar pretreatment, cAMP content was 320 +/- 31 or 140 +/- 25 f moles/mg, respectively, demonstrating an almost complete inhibition of the activity of the IgG to cause cAMP generation stimulation.", "contents": "Inactivation of human thyroid stimulator by human thyroid extract. To determine whether the thyroid stimulating activity of IGG of patients with Graves' disease is associated with the reaction with a putative human thyroid antigen, the inactivation of the property of IgG to stimulate cAMP generation in human thyroid slices incubated in vitro was studied by pretreating the IgG with human thyroidal particulate fraction. In the preliminary experiment, it was demonstrated that to cause cAMP generation stimulation, on incubation period of 120 min is required to allow the IgG to penetrate the tissue. When human thyroid slices were incubated with normal IgG without or with pretreatment by human thyroid particulate fraction obtained from 100 mg tissue, cAMP content in the slices was 142 +/- 25 or 138 +/- 26 f moles/mg, respectively, indicating that basal thyroidal cAMP levels were not influenced at all by normal IgG even after pretreatment with thyroid particulate fraction. When the slices were incubated with gG of Graves' disease without or with the similar pretreatment, cAMP content was 320 +/- 31 or 140 +/- 25 f moles/mg, respectively, demonstrating an almost complete inhibition of the activity of the IgG to cause cAMP generation stimulation."}
{"id": "PMID:225167", "title": "A case of histiocytosis X associated with panhypopituitarism and hyperimmunoglobulinemia G and E.", "content": "A 43 year old man with diabetes insipidus who showed panhypopituitarism and marked hypergammaglobulinemia due to histiocytosis X is reported. His low basal plasma adrenocorticotropin (ACTH) and growth hormone (GH) failed to respond to insulin-induced hypoglycemia. His basal serum thyroid hormone level was below normal and normal basal plasma thyrotropin (TSH) showed a delayed response with normal peak value to TSH-releasing hormone (TRH). Normal basal plasma pituitary gonadotropin also showed a delayed response with normal peak value to luteinizing hormone-releasing hormone (LH-RH). Suppression of plasma prolactin (PRL) by levodopa (l-dopa) was impaired and elevation of basal plasma PRL was noted at the second admission. These results, combined with diabetes insipidus, suggested that the panhypopituitarism in these patients was hypothalamic in origin. The polyclonal hypergammaglobulinemia was characterized by elevated serum IgG and IgE levels which returned to normal after corticosteroid treatment with concomitant clinical improvement. Elevated serum IgE levels, tissue and peripheral eosinophilia, and the effectiveness of corticosteroid therapy support the hypothesis that some allergic mechanism may be involved in the pathogenesis of this disease.", "contents": "A case of histiocytosis X associated with panhypopituitarism and hyperimmunoglobulinemia G and E. A 43 year old man with diabetes insipidus who showed panhypopituitarism and marked hypergammaglobulinemia due to histiocytosis X is reported. His low basal plasma adrenocorticotropin (ACTH) and growth hormone (GH) failed to respond to insulin-induced hypoglycemia. His basal serum thyroid hormone level was below normal and normal basal plasma thyrotropin (TSH) showed a delayed response with normal peak value to TSH-releasing hormone (TRH). Normal basal plasma pituitary gonadotropin also showed a delayed response with normal peak value to luteinizing hormone-releasing hormone (LH-RH). Suppression of plasma prolactin (PRL) by levodopa (l-dopa) was impaired and elevation of basal plasma PRL was noted at the second admission. These results, combined with diabetes insipidus, suggested that the panhypopituitarism in these patients was hypothalamic in origin. The polyclonal hypergammaglobulinemia was characterized by elevated serum IgG and IgE levels which returned to normal after corticosteroid treatment with concomitant clinical improvement. Elevated serum IgE levels, tissue and peripheral eosinophilia, and the effectiveness of corticosteroid therapy support the hypothesis that some allergic mechanism may be involved in the pathogenesis of this disease."}
{"id": "PMID:225168", "title": "C-peptide, insulin and proinsulinlike components in diabetic and nondiabetic human pancreas.", "content": "The contents of insulin and C-peptide extractable with acid alcohol from the tail of the pancreas and insulinoma were investigated, using gel filtration in seven nondiabetics including two patients with insulinoma and eight diabetics. The gel filtration patterns of both C-peptide and insulin in pancreatic extract were fairly stable even after the pancreas had been left for 14 hrs in the room temperature. In nondiabetics except cases of insulinoma the content of insulin in pancreas ranged from 1.42 to 4.56 U per gram and that of C-peptide from 8.76 to 25.63 microgram per gram wet pancreas. The proportion of proinsulinlike components (PLC) ranged from 0.01 to 2.04% of insulin plus PLC. In diabetics insulin content was low and ranged from 0 to 1.68 U per gram and that of C-peptide from 0 to 14.48 microgram per gram wet pancreas. In insulinoma, both insulin and C-peptide increased and PLC occupied 5.48 and 5.96%, respectively.", "contents": "C-peptide, insulin and proinsulinlike components in diabetic and nondiabetic human pancreas. The contents of insulin and C-peptide extractable with acid alcohol from the tail of the pancreas and insulinoma were investigated, using gel filtration in seven nondiabetics including two patients with insulinoma and eight diabetics. The gel filtration patterns of both C-peptide and insulin in pancreatic extract were fairly stable even after the pancreas had been left for 14 hrs in the room temperature. In nondiabetics except cases of insulinoma the content of insulin in pancreas ranged from 1.42 to 4.56 U per gram and that of C-peptide from 8.76 to 25.63 microgram per gram wet pancreas. The proportion of proinsulinlike components (PLC) ranged from 0.01 to 2.04% of insulin plus PLC. In diabetics insulin content was low and ranged from 0 to 1.68 U per gram and that of C-peptide from 0 to 14.48 microgram per gram wet pancreas. In insulinoma, both insulin and C-peptide increased and PLC occupied 5.48 and 5.96%, respectively."}
{"id": "PMID:225169", "title": "Insulin release and metabolism of calcium, adenine and adenosine 3',5'-cyclic monophosphate.", "content": "In order to assess further the mechanisms involved in insulin release, we prelabeled rat pancreatic islets of Langerhans by incubating either 45Ca or [2-3H]adenine. When prelabeled islets were perfused with a glucose-free medium (the experiment with 45Ca) and a medium containing 2.8 mM glucose (the experiment with [2-3H]adenine) respectively, a constant rate of efflux of the radioactivity was established by 30 min in each case. D-Glucose at 16.7 mM concentration elicited a rapid efflux of 45Ca and [2-3H]adenine derivatives ([3H]Ad) within 4 to 6 min after commencing the step-wise stimulation by glucose, concomitantly with insulin release. However, L-glucose and D-galactose littel stimulated both 45Ca and [3H]Ad release. Lanthanum chloride caused a burst peak of 45Ca release in the absence of glucose. A rapid efflux of 45Ca was caused by beta-D-glucose and D-glyceraldehyde to much lesser extent than by alpha-D-glucose. The slowly rising concentration of glucose at 0.1 mM/min of gradient level failed to elicit any rapid efflux of 45Ca or [3H]Ad, although insulin release occurred in accordance with an increase in glucose concentration. Even when the gradient of glucose concentration was raised to 0.7 mM/min, glucose failed to stimulate an efflux of [3H]Ad but the subsequent stimulation by 16.7 mM glucose caused a rapid efflux of [3H]Ad concomitantly with the release of insulin. No rapid efflux of 45Ca was observed under a slow-rise glucose stimulation until the gradient level of the glucose concentration was raised to 6.7 mM. Analysis of distribution of the radioactive adenine derivatives after incubation showed that the adenosine fraction had the highest radioactivity in the medium followed by the ATP, adenine and cAMP fraction in that order, and the ATP fraction had the highest radioactivity in the islet. The ratio of radioactivity in the cAMP fraction in the medium to the total count was the highest among all. On the basis of these results, it was suggested that the discharge of [3H]Ad and 45Ca might occur with the alteration of the membrane permeability induced by a rapid change of the glucose concentration, and that their discharge might perhaps link to the glucoreceptor mechanism directly controlling insulin release.", "contents": "Insulin release and metabolism of calcium, adenine and adenosine 3',5'-cyclic monophosphate. In order to assess further the mechanisms involved in insulin release, we prelabeled rat pancreatic islets of Langerhans by incubating either 45Ca or [2-3H]adenine. When prelabeled islets were perfused with a glucose-free medium (the experiment with 45Ca) and a medium containing 2.8 mM glucose (the experiment with [2-3H]adenine) respectively, a constant rate of efflux of the radioactivity was established by 30 min in each case. D-Glucose at 16.7 mM concentration elicited a rapid efflux of 45Ca and [2-3H]adenine derivatives ([3H]Ad) within 4 to 6 min after commencing the step-wise stimulation by glucose, concomitantly with insulin release. However, L-glucose and D-galactose littel stimulated both 45Ca and [3H]Ad release. Lanthanum chloride caused a burst peak of 45Ca release in the absence of glucose. A rapid efflux of 45Ca was caused by beta-D-glucose and D-glyceraldehyde to much lesser extent than by alpha-D-glucose. The slowly rising concentration of glucose at 0.1 mM/min of gradient level failed to elicit any rapid efflux of 45Ca or [3H]Ad, although insulin release occurred in accordance with an increase in glucose concentration. Even when the gradient of glucose concentration was raised to 0.7 mM/min, glucose failed to stimulate an efflux of [3H]Ad but the subsequent stimulation by 16.7 mM glucose caused a rapid efflux of [3H]Ad concomitantly with the release of insulin. No rapid efflux of 45Ca was observed under a slow-rise glucose stimulation until the gradient level of the glucose concentration was raised to 6.7 mM. Analysis of distribution of the radioactive adenine derivatives after incubation showed that the adenosine fraction had the highest radioactivity in the medium followed by the ATP, adenine and cAMP fraction in that order, and the ATP fraction had the highest radioactivity in the islet. The ratio of radioactivity in the cAMP fraction in the medium to the total count was the highest among all. On the basis of these results, it was suggested that the discharge of [3H]Ad and 45Ca might occur with the alteration of the membrane permeability induced by a rapid change of the glucose concentration, and that their discharge might perhaps link to the glucoreceptor mechanism directly controlling insulin release."}
{"id": "PMID:225171", "title": "The hormonal control of glycogen metabolism. Phosphorylation of protein phosphatase inhibitor-1 in vivo in response to adrenaline.", "content": "Inhibitor-1 has been shown to be phosphorylated in skeletal muscle in vivo. In normal fed animals the degree of phosphorylation was 31 +/- 7% and this value increases to 70 +/- 12% following an intravenous injection of adrenaline. The results imply that the phosphorylation of inhibitor-1 may be equally as important as the phosphorylation of phosphorylase kinase in elevating the levels of phosphorylase a. The role of inhibitor-1 in metabolism is discussed.", "contents": "The hormonal control of glycogen metabolism. Phosphorylation of protein phosphatase inhibitor-1 in vivo in response to adrenaline. Inhibitor-1 has been shown to be phosphorylated in skeletal muscle in vivo. In normal fed animals the degree of phosphorylation was 31 +/- 7% and this value increases to 70 +/- 12% following an intravenous injection of adrenaline. The results imply that the phosphorylation of inhibitor-1 may be equally as important as the phosphorylation of phosphorylase kinase in elevating the levels of phosphorylase a. The role of inhibitor-1 in metabolism is discussed."}
{"id": "PMID:225173", "title": "Nucleotide sequence of three isoaccepting lysine tRNAs from rabbit liver and SV40-transformed mouse fibroblasts.", "content": "The lysine isoacceptor tRNAs differ in two aspects from the majority of the other mammalian tRNA species: they do not contain ribosylthymine (T) in loop IV, and a 'new' lysine tRNA, which is practically absent in non-dividing tissue, appears at elevated levels in proliferating cells. We have therefore purified the three major isoaccepting lysine tRNAs from rabbit liver and the 'new' lysine tRNA isolated from SV40-transformed mouse fibroblasts, and determined their nucleotide sequences. Our basic findings are as follows. a) The three major lysine tRNAs (species 1, 2 and 3) from rabbit liver contain 2'-O-methylribosylthymine (Tm) in place of T. tRNA1Lys and tRNA2Lys differ only by a single base pair in the middle of the anticodon stem; the anticodon sequence C-U-U is followed by N-threonyl-adenosine (t6A). TRNA3Lys has the anticodon S-U-U and contains two highly modified thionucleosides, S (shown to be 2-thio-5-carboxymethyl-uridine methyl ester) and a further modified derivative of t6 A (2-methyl-thio-N6-threonyl-adenosine) on the 3' side of the anticodon. tRNA3Lys differs in 14 and 16 positions, respectively, from the other two isoacceptors. b) Protein synthesis in vitro, using synthetic polynucleotides of defined sequence, showed that tRNA2Lys with anticodon C-U-U recognized A-A-G only, whereas tRNA3Lys, which contains thio-nucleotides in and next to the anticodon, decodes both lysine codons A-A-G and A-A-A, but with a preference for A-A-A. In a globin-mRNA-translating cell-free system from ascites cells, both lysine tRNAs donated lysine into globin. The rate and extent of lysine incorporation, however, was higher with tRNA2Lys than with tRNA3Lys, in agreement with the fact that alpha-globin and beta-globin mRNAs contain more A-A-G than A-A-A- codons for lysine. c) A comparison of the nucleotide sequences of lysine tRNA species 1, 2 and 3 from rabbit liver, with that of the 'new' tRNA4Lys from transformed and rapidly dividing cells showed that this tRNA is not the product of a new gene or group of genes, but is an undermodified tRNA derived exclusively from tRNA2Lys. Of the two dihydrouridines present in tRNA2Lys, one is found as U in tRNA4Lys; the purine next to the anticodon is as yet unidentified but is known not be t6 A. In addition we have found U, T and psi besides Tm as the first nucleoside in loop IV.", "contents": "Nucleotide sequence of three isoaccepting lysine tRNAs from rabbit liver and SV40-transformed mouse fibroblasts. The lysine isoacceptor tRNAs differ in two aspects from the majority of the other mammalian tRNA species: they do not contain ribosylthymine (T) in loop IV, and a 'new' lysine tRNA, which is practically absent in non-dividing tissue, appears at elevated levels in proliferating cells. We have therefore purified the three major isoaccepting lysine tRNAs from rabbit liver and the 'new' lysine tRNA isolated from SV40-transformed mouse fibroblasts, and determined their nucleotide sequences. Our basic findings are as follows. a) The three major lysine tRNAs (species 1, 2 and 3) from rabbit liver contain 2'-O-methylribosylthymine (Tm) in place of T. tRNA1Lys and tRNA2Lys differ only by a single base pair in the middle of the anticodon stem; the anticodon sequence C-U-U is followed by N-threonyl-adenosine (t6A). TRNA3Lys has the anticodon S-U-U and contains two highly modified thionucleosides, S (shown to be 2-thio-5-carboxymethyl-uridine methyl ester) and a further modified derivative of t6 A (2-methyl-thio-N6-threonyl-adenosine) on the 3' side of the anticodon. tRNA3Lys differs in 14 and 16 positions, respectively, from the other two isoacceptors. b) Protein synthesis in vitro, using synthetic polynucleotides of defined sequence, showed that tRNA2Lys with anticodon C-U-U recognized A-A-G only, whereas tRNA3Lys, which contains thio-nucleotides in and next to the anticodon, decodes both lysine codons A-A-G and A-A-A, but with a preference for A-A-A. In a globin-mRNA-translating cell-free system from ascites cells, both lysine tRNAs donated lysine into globin. The rate and extent of lysine incorporation, however, was higher with tRNA2Lys than with tRNA3Lys, in agreement with the fact that alpha-globin and beta-globin mRNAs contain more A-A-G than A-A-A- codons for lysine. c) A comparison of the nucleotide sequences of lysine tRNA species 1, 2 and 3 from rabbit liver, with that of the 'new' tRNA4Lys from transformed and rapidly dividing cells showed that this tRNA is not the product of a new gene or group of genes, but is an undermodified tRNA derived exclusively from tRNA2Lys. Of the two dihydrouridines present in tRNA2Lys, one is found as U in tRNA4Lys; the purine next to the anticodon is as yet unidentified but is known not be t6 A. In addition we have found U, T and psi besides Tm as the first nucleoside in loop IV."}
{"id": "PMID:225174", "title": "Characterization of an adenosine triphosphatase from myeloblasts infected with the avian myeloblastosis virus.", "content": "An adenosine triphosphatase (ATPase EC 3.6.1.3) was partially purified from myeloblasts of chicken infected with the avian myeloblastosis virus and some of its molecular, catalytic and immunological properties were compared with that of the ATPase purified from the virus. Both the enzymes possessed almost same electrophoretic mobility, molecular weight, S20,w value, substrate specificity, metal-ion requirement, apparent Km value and sensitivity to inhibitors and activator. Evidence also indicated immunological identity of the two enzymes. The insensitivity of this enzyme to rutamycin or ouabain and extreme sensitivity to most of the detergents, trypsin and mercurials are the remarkable properties of this enzyme.", "contents": "Characterization of an adenosine triphosphatase from myeloblasts infected with the avian myeloblastosis virus. An adenosine triphosphatase (ATPase EC 3.6.1.3) was partially purified from myeloblasts of chicken infected with the avian myeloblastosis virus and some of its molecular, catalytic and immunological properties were compared with that of the ATPase purified from the virus. Both the enzymes possessed almost same electrophoretic mobility, molecular weight, S20,w value, substrate specificity, metal-ion requirement, apparent Km value and sensitivity to inhibitors and activator. Evidence also indicated immunological identity of the two enzymes. The insensitivity of this enzyme to rutamycin or ouabain and extreme sensitivity to most of the detergents, trypsin and mercurials are the remarkable properties of this enzyme."}
{"id": "PMID:225175", "title": "Cyclic 3',5'-adenosine monophosphate (cAMP) in a 42-month-old child with clinical evidence of multiple hormonal disturbances.", "content": "In a boy aged 42 months, small stature, retarded psychomotor development, dry skin, excessive thirst, polyuria, cryptorchidism, and rickets were signs of multihormonal disturbances. Contrary to the clinical manifestations, laboratory investigations showed normal or raised levels of hormones (hGH, insulin, T3RU, T4, TSH, PTH). The cAMP level in the plasma was low and its urinary excretion was reduced. After administration of hGH, adrenaline, T3, T4, pitressin, vitamin D3 and aminophylline there was no rise in the cAMP concentration in plasma and urine. In the light of these results it may be assumed that deficient function of the adenyl cyclase system led to development of a clinical syndrome of tissue insensitivity to multiple hormonal factors in this case.", "contents": "Cyclic 3',5'-adenosine monophosphate (cAMP) in a 42-month-old child with clinical evidence of multiple hormonal disturbances. In a boy aged 42 months, small stature, retarded psychomotor development, dry skin, excessive thirst, polyuria, cryptorchidism, and rickets were signs of multihormonal disturbances. Contrary to the clinical manifestations, laboratory investigations showed normal or raised levels of hormones (hGH, insulin, T3RU, T4, TSH, PTH). The cAMP level in the plasma was low and its urinary excretion was reduced. After administration of hGH, adrenaline, T3, T4, pitressin, vitamin D3 and aminophylline there was no rise in the cAMP concentration in plasma and urine. In the light of these results it may be assumed that deficient function of the adenyl cyclase system led to development of a clinical syndrome of tissue insensitivity to multiple hormonal factors in this case."}
{"id": "PMID:225176", "title": "Reduced high density lipoprotein in stroke: relationship with elevated triglyceride and hypertension.", "content": "Lipids and lipoproteins were analysed in forty-one survivors of stroke, aged less than 65 years, and the same number of age and sex matched controls without vascular disease. The stroke subjects had no evidence of coronary artery or peripheral vascular disease. High density lipoprotein cholesterol was significantly lower (1.19 +/- 0.06 mmol/l) in the stroke subjects than the controls (1.47 +/- 0.07 mmol/l). Triglyceride was also elevated in the stroke subjects, but this was confined to those who were taking antihypertensive treatment which included beta-blockers and/or thiazides. The low levels of high density lipoprotein in stroke were independent of hypertension or its treatment. Thus low levels of high density lipoprotein appear to be associated with cerebrovascular disease, while elevated triglyceride is a complication of anti-hypertensive therapy.", "contents": "Reduced high density lipoprotein in stroke: relationship with elevated triglyceride and hypertension. Lipids and lipoproteins were analysed in forty-one survivors of stroke, aged less than 65 years, and the same number of age and sex matched controls without vascular disease. The stroke subjects had no evidence of coronary artery or peripheral vascular disease. High density lipoprotein cholesterol was significantly lower (1.19 +/- 0.06 mmol/l) in the stroke subjects than the controls (1.47 +/- 0.07 mmol/l). Triglyceride was also elevated in the stroke subjects, but this was confined to those who were taking antihypertensive treatment which included beta-blockers and/or thiazides. The low levels of high density lipoprotein in stroke were independent of hypertension or its treatment. Thus low levels of high density lipoprotein appear to be associated with cerebrovascular disease, while elevated triglyceride is a complication of anti-hypertensive therapy."}
{"id": "PMID:225177", "title": "Selective labeling of apomorphine receptors by 3H-LSD.", "content": "There are at least two types of dopamine receptors: the 3H-dopamine or 3H-apomorphine receptor (with high or nM affinity for dopamine), and the 3H-neuroleptic receptor (with low or microM affinity for dopamine). While 3H-LSD can label the 3H-neuroleptic receptor, this study was done in order to label the 3H-apomorphine/dopamine receptor site. In the presence of excess phentolamine, serotonin and spiperone (to preclude binding to alpha-adrenergic, serotonergic and neuroleptic receptors, respectively) similar concentrations of dopaminergic drugs inhibited the binding (to calf caudate) of 3H-LSD and 3H-apomorphine. This is compatible with the concept that the 3H-apomorphine/dopamine receptor and the 3H-neuroleptic/dopamine receptor are separate.", "contents": "Selective labeling of apomorphine receptors by 3H-LSD. There are at least two types of dopamine receptors: the 3H-dopamine or 3H-apomorphine receptor (with high or nM affinity for dopamine), and the 3H-neuroleptic receptor (with low or microM affinity for dopamine). While 3H-LSD can label the 3H-neuroleptic receptor, this study was done in order to label the 3H-apomorphine/dopamine receptor site. In the presence of excess phentolamine, serotonin and spiperone (to preclude binding to alpha-adrenergic, serotonergic and neuroleptic receptors, respectively) similar concentrations of dopaminergic drugs inhibited the binding (to calf caudate) of 3H-LSD and 3H-apomorphine. This is compatible with the concept that the 3H-apomorphine/dopamine receptor and the 3H-neuroleptic/dopamine receptor are separate."}
{"id": "PMID:225178", "title": "Effect of chronic ethanol treatment on specific [3H]ouabain binding to (Na+ + K+)-ATPase in different areas of cat brain.", "content": "Chronic ethanol administration to cats increased specific [3H]ouabain binding by 63% in cerebral cortex, 47% in cerebellum, 84% in amygdala, and 100% in hippocampus when the binding assays were performed in the presence of 160 nM [3H]ouabain. There was no significant change in specific [3H]ouabain binding in hypothalamus, thalamus, corpus striatum, and brain stem following chronic ethanol ingestion. Scatchard analysis revealed that enhancement of specific [3H]ouabain binding following chronic ethanol treatment in some areas of cat brain is primarily due to changes in densities of ouabain binding sites. Since ouabain is a specific inhibitor of (Na+ + K+)-ATPase the present observations suggest that the molecular mechanism for the enhancement of (Na+ + K+)-ATPase activity after chronic ethanol ingestion may be due to increased net rate of synthesis of (Na+ + K+)-ATPase molecules or exposure of non-functional enzyme system following conformational change of plasma membrane.", "contents": "Effect of chronic ethanol treatment on specific [3H]ouabain binding to (Na+ + K+)-ATPase in different areas of cat brain. Chronic ethanol administration to cats increased specific [3H]ouabain binding by 63% in cerebral cortex, 47% in cerebellum, 84% in amygdala, and 100% in hippocampus when the binding assays were performed in the presence of 160 nM [3H]ouabain. There was no significant change in specific [3H]ouabain binding in hypothalamus, thalamus, corpus striatum, and brain stem following chronic ethanol ingestion. Scatchard analysis revealed that enhancement of specific [3H]ouabain binding following chronic ethanol treatment in some areas of cat brain is primarily due to changes in densities of ouabain binding sites. Since ouabain is a specific inhibitor of (Na+ + K+)-ATPase the present observations suggest that the molecular mechanism for the enhancement of (Na+ + K+)-ATPase activity after chronic ethanol ingestion may be due to increased net rate of synthesis of (Na+ + K+)-ATPase molecules or exposure of non-functional enzyme system following conformational change of plasma membrane."}
{"id": "PMID:225180", "title": "GABA receptor-mediated modulation of 3H-diazepam binding in rat cortex.", "content": "Three membrane preparations of rat cortex were used to examine the effects of GABA, bicuculline and bicucine on specific 3H-diazepam binding. In the crude synaptosomal fraction, GABA had no effect on either the maximal binding capacity (Bmax) or dissociation constant (KD) of 3H-diazepam binding. Bicuculline and bicucine both decreased binding affinity. This was antagonized by adding GABA. In the repeatedly washed membrane preparation, and in the washed, frozen and thawed preparation, GABA increased binding affinity and, at high concentrations, increased Bmax. Increased binding affinity was observed with as little as 10(-8) M GABA in the washed, frozen and thawed preparation. Bicuculline inhibited the effect of GABA on 3H-diazepam binding. It was found that about 3 X 10(-5) M GABA was present in the assay medium containing crude synaptosomal fraction. These results suggest endogenous GABA is present in, and influences the results of 3H-diazepam binding assays. Furthermore, it appears that GABA and bicuculline affect 3H-diazepam binding through their binding to the specific GABA binding site.", "contents": "GABA receptor-mediated modulation of 3H-diazepam binding in rat cortex. Three membrane preparations of rat cortex were used to examine the effects of GABA, bicuculline and bicucine on specific 3H-diazepam binding. In the crude synaptosomal fraction, GABA had no effect on either the maximal binding capacity (Bmax) or dissociation constant (KD) of 3H-diazepam binding. Bicuculline and bicucine both decreased binding affinity. This was antagonized by adding GABA. In the repeatedly washed membrane preparation, and in the washed, frozen and thawed preparation, GABA increased binding affinity and, at high concentrations, increased Bmax. Increased binding affinity was observed with as little as 10(-8) M GABA in the washed, frozen and thawed preparation. Bicuculline inhibited the effect of GABA on 3H-diazepam binding. It was found that about 3 X 10(-5) M GABA was present in the assay medium containing crude synaptosomal fraction. These results suggest endogenous GABA is present in, and influences the results of 3H-diazepam binding assays. Furthermore, it appears that GABA and bicuculline affect 3H-diazepam binding through their binding to the specific GABA binding site."}
{"id": "PMID:225181", "title": "Effect of serotonin on cyclic AMP level in rat hypothalamus slices during development.", "content": "The effect of serotonin (5-HT) on cyclic AMP levels in rat hypothalamic slices was age-dependent. The sensitivity of the cyclic AMP system to 5 X 10(-5) M 5-HT already existed in the foetus at 21 days of pregnancy. It reached a maximum on the 7th postnatal day and then decreased with age. In adult tissue the response was still present and was antagonized by two serotonergic antagonists (methiothepin and metergoline). When compared to the progressive increase of 5-HT level in the hypothalamus the data suggest a different evolution of serotonergic innervation and of 5-HT receptors.", "contents": "Effect of serotonin on cyclic AMP level in rat hypothalamus slices during development. The effect of serotonin (5-HT) on cyclic AMP levels in rat hypothalamic slices was age-dependent. The sensitivity of the cyclic AMP system to 5 X 10(-5) M 5-HT already existed in the foetus at 21 days of pregnancy. It reached a maximum on the 7th postnatal day and then decreased with age. In adult tissue the response was still present and was antagonized by two serotonergic antagonists (methiothepin and metergoline). When compared to the progressive increase of 5-HT level in the hypothalamus the data suggest a different evolution of serotonergic innervation and of 5-HT receptors."}
{"id": "PMID:225182", "title": "Inhibition of fundic strips from guinea-pig stomach: the effect of theophylline on the membrane potential, muscle contraction and ion fluxes.", "content": "The effect of theophylline on the smooth muscle cells of the fundic part of the stomach of the guinea pig was investigated. Theophylline hyperpolarized the membrane, inhibited spike discharges and slow waves and produced relaxation of the muscle cells. Furthermore, the theophylline-induced relaxation was not affected in low sodium solution or during inhibition of the sodium pump. Partial inhibition of the theophylline relaxation was seen in muscle depolarized by a high potassium solution and also when ATP was the relaxant. The potassium efflux was enhanced by ATP, but was not markedly changed by theophylline. A change in calcium efflux in the presence of theophylline could not be measured in quiescent preparations. The calcium influx was not changed by theophylline in Krebs, by low Ca, or by high K solution. Furthermore, the tissue content of cyclic AMP was increased by 59.6% in the presence of theophylline (2 x 10(-3) M). The conclusion is reached that the most likely mode of action of theophylline is a suppression of spontaneous activity and an extensive calcium binding to internal sites.", "contents": "Inhibition of fundic strips from guinea-pig stomach: the effect of theophylline on the membrane potential, muscle contraction and ion fluxes. The effect of theophylline on the smooth muscle cells of the fundic part of the stomach of the guinea pig was investigated. Theophylline hyperpolarized the membrane, inhibited spike discharges and slow waves and produced relaxation of the muscle cells. Furthermore, the theophylline-induced relaxation was not affected in low sodium solution or during inhibition of the sodium pump. Partial inhibition of the theophylline relaxation was seen in muscle depolarized by a high potassium solution and also when ATP was the relaxant. The potassium efflux was enhanced by ATP, but was not markedly changed by theophylline. A change in calcium efflux in the presence of theophylline could not be measured in quiescent preparations. The calcium influx was not changed by theophylline in Krebs, by low Ca, or by high K solution. Furthermore, the tissue content of cyclic AMP was increased by 59.6% in the presence of theophylline (2 x 10(-3) M). The conclusion is reached that the most likely mode of action of theophylline is a suppression of spontaneous activity and an extensive calcium binding to internal sites."}
{"id": "PMID:225183", "title": "[Seromonitoring of laboratory mouse and rat colonies for common murine pathogens (author's transl)].", "content": "During a period from 1973 to 1978, 392 and 225 lots including 12,232 mouse and 8,044 rat individual sera, respectively, were examined for antibodies to murine hepatitis virus, Sendai virus, Bordetella bronchiseptica, Mycoplasma pulmonis, Tyzzer agents, Salmonella typhimurium and Corynebacterium kutscheri. Of mouse lots 94.5% and 39.3% from breeder and user colonies, respectively, were negative for all antibodies examined as well as 31.6% and 17.2% of rat breeder and user colonies, respectively. Among positive lots from mouse users, high positivity rates were seen with Senai virus (47.6%), M. pulmonis (19.0%), and murine hepatitis virus (JHM : 18.2%, MHV : 31.0%), while the rates were high in rat user lots with Sendai virus (24.4%), B. bronchiseptica (39.3%) M. pulmonis (12.5%), murine coronaviruses (JHM : 19.0%, MHV-2 : 28.0%) and tyzzer agents (MSK : 19.6%, RT : 17.9%). These pathogenes with high positivities should be monitored indispensably as a quality control of laboratory mice and rats.", "contents": "[Seromonitoring of laboratory mouse and rat colonies for common murine pathogens (author's transl)]. During a period from 1973 to 1978, 392 and 225 lots including 12,232 mouse and 8,044 rat individual sera, respectively, were examined for antibodies to murine hepatitis virus, Sendai virus, Bordetella bronchiseptica, Mycoplasma pulmonis, Tyzzer agents, Salmonella typhimurium and Corynebacterium kutscheri. Of mouse lots 94.5% and 39.3% from breeder and user colonies, respectively, were negative for all antibodies examined as well as 31.6% and 17.2% of rat breeder and user colonies, respectively. Among positive lots from mouse users, high positivity rates were seen with Senai virus (47.6%), M. pulmonis (19.0%), and murine hepatitis virus (JHM : 18.2%, MHV : 31.0%), while the rates were high in rat user lots with Sendai virus (24.4%), B. bronchiseptica (39.3%) M. pulmonis (12.5%), murine coronaviruses (JHM : 19.0%, MHV-2 : 28.0%) and tyzzer agents (MSK : 19.6%, RT : 17.9%). These pathogenes with high positivities should be monitored indispensably as a quality control of laboratory mice and rats."}
{"id": "PMID:225188", "title": "Factors promoting colony stimulating activity (CSA) production in macrophages and epithelial cells.", "content": "The regulation of colony stimulating activity (CSA) release from CSA producing cells is a poorly understood process. Using freshly isolated mouse peritoneal cells and a continuous line of mouse thymic epithelial cells a precise and reproducible method of short term culture was developed to study this phenomenon. Serum, endotoxin, lithium, and cyclic GMP stimulated CSA release from both cell types. Particles such as zymosan, inulin, latex, and iron filings stimulated CSA release from mouse peritoneal cells but not from thymic epthelial cells. Theophylline and cyclic AMP inhibited CSA release from both cell types. Trypsin activated guinea pig C3 and C5 did not stimulate CSA release. Cycloheximide, an inhibitor of protein synthesis, completely inhibited CSA release. We believe these findings may reflect mechanisms of in vivo regulation of CSA release.", "contents": "Factors promoting colony stimulating activity (CSA) production in macrophages and epithelial cells. The regulation of colony stimulating activity (CSA) release from CSA producing cells is a poorly understood process. Using freshly isolated mouse peritoneal cells and a continuous line of mouse thymic epithelial cells a precise and reproducible method of short term culture was developed to study this phenomenon. Serum, endotoxin, lithium, and cyclic GMP stimulated CSA release from both cell types. Particles such as zymosan, inulin, latex, and iron filings stimulated CSA release from mouse peritoneal cells but not from thymic epthelial cells. Theophylline and cyclic AMP inhibited CSA release from both cell types. Trypsin activated guinea pig C3 and C5 did not stimulate CSA release. Cycloheximide, an inhibitor of protein synthesis, completely inhibited CSA release. We believe these findings may reflect mechanisms of in vivo regulation of CSA release."}
{"id": "PMID:225190", "title": "Cyclic AMP mediated activity stimulation by metronidazole in rat liver.", "content": "In the homogenate of the liver biochemically examined 45 hrs after a single 250 mg dose of metronidazole administration, a 45% increase of c-AMP level was found as compared with controls. A marked proliferation of hepatic smooth endoplasmic reticulum was observed. In the light microscope numerous mitotic figures could be seen. No mitotic figures were present in the liver tissue of either treated or untreated animals examined 24, 72 and 120 hrs post administration of metronidazole. Two points seem of interest in the biologic properties of metronidazole: one is the participation of hepatic smooth endoplasmic reticulum in its metabolism, the other--the formation of active metabolites which may posses carcinogenous properties.", "contents": "Cyclic AMP mediated activity stimulation by metronidazole in rat liver. In the homogenate of the liver biochemically examined 45 hrs after a single 250 mg dose of metronidazole administration, a 45% increase of c-AMP level was found as compared with controls. A marked proliferation of hepatic smooth endoplasmic reticulum was observed. In the light microscope numerous mitotic figures could be seen. No mitotic figures were present in the liver tissue of either treated or untreated animals examined 24, 72 and 120 hrs post administration of metronidazole. Two points seem of interest in the biologic properties of metronidazole: one is the participation of hepatic smooth endoplasmic reticulum in its metabolism, the other--the formation of active metabolites which may posses carcinogenous properties."}
{"id": "PMID:225191", "title": "Rat endo- and mesothelium lack Fc receptors.", "content": "The present study is concerned with the interaction of rat endo- and mesothelium with homologous erythrocytes under various conditions of pretreatment and incubation. Its findings show rat endo- and mesothelial cells a) nonadhesive to native or pretreated erythrocytes irrespective of the presence of gamma-globulin in the medium, b) devoid of primary or cryptic receptors sensitive to the Fc segment of the IgG molecule, and c) provided with binding sites at the oxidized glycocalyx which together with receptor groups of modified erythrocytes share the same class of IgG.", "contents": "Rat endo- and mesothelium lack Fc receptors. The present study is concerned with the interaction of rat endo- and mesothelium with homologous erythrocytes under various conditions of pretreatment and incubation. Its findings show rat endo- and mesothelial cells a) nonadhesive to native or pretreated erythrocytes irrespective of the presence of gamma-globulin in the medium, b) devoid of primary or cryptic receptors sensitive to the Fc segment of the IgG molecule, and c) provided with binding sites at the oxidized glycocalyx which together with receptor groups of modified erythrocytes share the same class of IgG."}
{"id": "PMID:225192", "title": "Effect of sodium butyrate in combination with X-irradiation, chemotherapeutic and cyclic AMP stimulating agents on neuroblastoma cells in culture.", "content": "Sodium butyrate, X-irradiation, chemotherapeutic agents and cyclic AMP-stimulating agents cuased reduction in the cell number (due to cell death and reduction in cell division) when added individually to mouse neuroblastoma cells in culture. However, the combination of sodium butyrate with X-irradiation, chemotherapeutic and cyclic AMP-stimulating agents produced a greater reduction in the cell number than that produced by the individual agents.", "contents": "Effect of sodium butyrate in combination with X-irradiation, chemotherapeutic and cyclic AMP stimulating agents on neuroblastoma cells in culture. Sodium butyrate, X-irradiation, chemotherapeutic agents and cyclic AMP-stimulating agents cuased reduction in the cell number (due to cell death and reduction in cell division) when added individually to mouse neuroblastoma cells in culture. However, the combination of sodium butyrate with X-irradiation, chemotherapeutic and cyclic AMP-stimulating agents produced a greater reduction in the cell number than that produced by the individual agents."}
{"id": "PMID:225193", "title": "Effects of cadmium on the immune system of mice.", "content": "Chronic oral exposure of mice to Cd++ inhibits cell-mediated immunity of delayed type hypersensitivity induced by sheep red blood cells (SRBC). No effect was detected on humoral immune response to SRBC. Spleen cells derived from mice exposed to Cd++ showed in vitro enhanced response to T and B cell mitogens. These results demonstrate that Cd++ exposure alters the immune system of mice.", "contents": "Effects of cadmium on the immune system of mice. Chronic oral exposure of mice to Cd++ inhibits cell-mediated immunity of delayed type hypersensitivity induced by sheep red blood cells (SRBC). No effect was detected on humoral immune response to SRBC. Spleen cells derived from mice exposed to Cd++ showed in vitro enhanced response to T and B cell mitogens. These results demonstrate that Cd++ exposure alters the immune system of mice."}
{"id": "PMID:225194", "title": "Regional and strain variation in brain 3':5' cyclic adenosine monophosphate of inbred mice.", "content": "Regional variations were found in cAMP levels in flash frozen mouse brains with the pons and cerebellum having higher levels than the cerebrum. There were also strain variations with CBA/J and BALB/cJ having higher levels than C57B1/6J in the pons and cerebellum.", "contents": "Regional and strain variation in brain 3':5' cyclic adenosine monophosphate of inbred mice. Regional variations were found in cAMP levels in flash frozen mouse brains with the pons and cerebellum having higher levels than the cerebrum. There were also strain variations with CBA/J and BALB/cJ having higher levels than C57B1/6J in the pons and cerebellum."}
{"id": "PMID:225195", "title": "Possible mechanism of rubidium-induced hyperactivity in the rat.", "content": "This study suggests that replacement of intracellular potassium by rubidium ions might lower the resting membrane potential. Thus rubidium-treated rats were more responsive to depolarizing influences and generated more cyclic AMP in the brainstem and consequently the behavioral changes.", "contents": "Possible mechanism of rubidium-induced hyperactivity in the rat. This study suggests that replacement of intracellular potassium by rubidium ions might lower the resting membrane potential. Thus rubidium-treated rats were more responsive to depolarizing influences and generated more cyclic AMP in the brainstem and consequently the behavioral changes."}
{"id": "PMID:225200", "title": "[Homoanalogues of pyrimidine nucleosides. XII. 3,6-anhydro-1,2-bis-desoxy-1-(pyrimidin- and 5-halopyrimidin-1-yl)-D-arabinohexitols; 3,6-anhydro-1-desoxy-1(5-halopyrimidin-1-yl)-D-glucitols].", "content": "Lithium aluminium hydride reduction of 3,6-anhydro-1-o-benzoyl-4,5-o-isopropylidene-2-o-p-tolylsulfonyl-D-mannitol (II) gives with 74% yield 3,6-anhydro-2-deoxy-4,5-o-isopropylidene-D-arabino-hexitol (III). This compound is used as its corresponding 1-o-p-toluene-sulfonate (IV) for the N-1 alkylation of uracil, 5-fluorouracil, thymine and N-acetylcytosine. Acidic cleavage of the acetal protecting group gives the expected bis-homoanalogues of the pyrimidine- and halopyrimidine-nucleosides (V-VIII) which are characterized mainly through their mass spectra and U.V. absorption. 3,6-Anhydro-1,2-dideoxy-1-(5-bromo- and 5-iodouracil-1-yl)-D-arabino-hexitols (XIII, XIV), 3,6-anhydro-1-deoxy-1-(5-bromo- and 5-iodouracil-1-yl)-D-glucitols (XV, XVI) are similarly prepared by direct halogenation of the corresponding uracil derivatives. Results of cytotoxic, cytostatic and antiviral tests are described.", "contents": "[Homoanalogues of pyrimidine nucleosides. XII. 3,6-anhydro-1,2-bis-desoxy-1-(pyrimidin- and 5-halopyrimidin-1-yl)-D-arabinohexitols; 3,6-anhydro-1-desoxy-1(5-halopyrimidin-1-yl)-D-glucitols]. Lithium aluminium hydride reduction of 3,6-anhydro-1-o-benzoyl-4,5-o-isopropylidene-2-o-p-tolylsulfonyl-D-mannitol (II) gives with 74% yield 3,6-anhydro-2-deoxy-4,5-o-isopropylidene-D-arabino-hexitol (III). This compound is used as its corresponding 1-o-p-toluene-sulfonate (IV) for the N-1 alkylation of uracil, 5-fluorouracil, thymine and N-acetylcytosine. Acidic cleavage of the acetal protecting group gives the expected bis-homoanalogues of the pyrimidine- and halopyrimidine-nucleosides (V-VIII) which are characterized mainly through their mass spectra and U.V. absorption. 3,6-Anhydro-1,2-dideoxy-1-(5-bromo- and 5-iodouracil-1-yl)-D-arabino-hexitols (XIII, XIV), 3,6-anhydro-1-deoxy-1-(5-bromo- and 5-iodouracil-1-yl)-D-glucitols (XV, XVI) are similarly prepared by direct halogenation of the corresponding uracil derivatives. Results of cytotoxic, cytostatic and antiviral tests are described."}
{"id": "PMID:225198", "title": "[Effect of preparations that alter the cyclic nucleotide level on acetylation processes].", "content": "The action of stimulants and imitators of the adenylate cyclase function (novodrin, sodium fluoride, cAMP), imitators of the guanylcyclase function (cGMP), inhibitors of adenylate cyclase (propranolol), izanylate cyclase (atropin) or phosphodiesterase (euphyllin, papaverin) on the body acetylating capacity measured from acetyl-PABA release, and CoA content in the liver was studied in experiments on male rats. The substances that mainly produce an increase in cAMP in the tissues augment the CoA endogenic pool and, as a rule, stimulate the acetylating capacity of the body. As compared to cAMP, the eczogenic cGMP raises, but to a significantly less measure, the CoA content and does not change the rate of arylamine acetylation. Paraverin is an exception to the rule since it seems to exert a direct action on the enzymatic system of acetylation. When administered to rats cGMP elicits a cAMP-like but a weaker action on the CoA pool. It is suggested that combined use of test substances prolonging cAMP effects and drugs belonging to a group of arylamines is not advisable because of active inactivation of the latter compounds.", "contents": "[Effect of preparations that alter the cyclic nucleotide level on acetylation processes]. The action of stimulants and imitators of the adenylate cyclase function (novodrin, sodium fluoride, cAMP), imitators of the guanylcyclase function (cGMP), inhibitors of adenylate cyclase (propranolol), izanylate cyclase (atropin) or phosphodiesterase (euphyllin, papaverin) on the body acetylating capacity measured from acetyl-PABA release, and CoA content in the liver was studied in experiments on male rats. The substances that mainly produce an increase in cAMP in the tissues augment the CoA endogenic pool and, as a rule, stimulate the acetylating capacity of the body. As compared to cAMP, the eczogenic cGMP raises, but to a significantly less measure, the CoA content and does not change the rate of arylamine acetylation. Paraverin is an exception to the rule since it seems to exert a direct action on the enzymatic system of acetylation. When administered to rats cGMP elicits a cAMP-like but a weaker action on the CoA pool. It is suggested that combined use of test substances prolonging cAMP effects and drugs belonging to a group of arylamines is not advisable because of active inactivation of the latter compounds."}
{"id": "PMID:225216", "title": "Trials with xanthine derivatives in systemic treatment of psoriasis.", "content": "The psoriatic epidermis is more active metabolically and its rate of proliferation is faster, showing incomplete differentiation as a result of the imbalance between the low level of cyclic AMP and the high level of cyclic GMP. The low cyclic AMP levels are due to hyperactivity of the phosphodiesterase which hydrolyzes cyclic AMP. Xanthine derivatives are found to be potent phosphodiesterase inhibitors. 15 psoriatic patients were treated with tablets of xanthine derivatives (dyphylline, aminophylline). The obtained results are discussed.", "contents": "Trials with xanthine derivatives in systemic treatment of psoriasis. The psoriatic epidermis is more active metabolically and its rate of proliferation is faster, showing incomplete differentiation as a result of the imbalance between the low level of cyclic AMP and the high level of cyclic GMP. The low cyclic AMP levels are due to hyperactivity of the phosphodiesterase which hydrolyzes cyclic AMP. Xanthine derivatives are found to be potent phosphodiesterase inhibitors. 15 psoriatic patients were treated with tablets of xanthine derivatives (dyphylline, aminophylline). The obtained results are discussed."}
{"id": "PMID:225217", "title": "[On neurogenic granular cells and their relationships to the so-called granular cell myoblastoma (author's transl)].", "content": "A report on granular cells found in biopsy material is presented. Morphologically identical patterns were seen in a pigmentated granular 'rankenneuroma' and in a patient with a morphea of the tongue. The independent development of granular cells in tumorous and nontumorous tissue supports the idea that the so-called granular cell myoblastoma originates from degenerative alterations of Schwann cells.", "contents": "[On neurogenic granular cells and their relationships to the so-called granular cell myoblastoma (author's transl)]. A report on granular cells found in biopsy material is presented. Morphologically identical patterns were seen in a pigmentated granular 'rankenneuroma' and in a patient with a morphea of the tongue. The independent development of granular cells in tumorous and nontumorous tissue supports the idea that the so-called granular cell myoblastoma originates from degenerative alterations of Schwann cells."}
{"id": "PMID:225218", "title": "[Plasma cortisol response to intravenous beta 1-24 corticotropin as related to the fat mass and its topographic localisation (author's transl)].", "content": "Plasma cortisol response induced by 2.5 microgram/kg beta 1-24 corticotropin (1 hour infusion) in obese females was not related to fat mass. The response was increasingly pronounced as fat predominated in the upper body segment, i.e. android obesity. This phenomenon may be interpreted as indicating an increased adrenal capacity to secrete cortisol in such obese patients. Low level but longstanding excess cortisol secretion is probably the cause of the android features of obesity.", "contents": "[Plasma cortisol response to intravenous beta 1-24 corticotropin as related to the fat mass and its topographic localisation (author's transl)]. Plasma cortisol response induced by 2.5 microgram/kg beta 1-24 corticotropin (1 hour infusion) in obese females was not related to fat mass. The response was increasingly pronounced as fat predominated in the upper body segment, i.e. android obesity. This phenomenon may be interpreted as indicating an increased adrenal capacity to secrete cortisol in such obese patients. Low level but longstanding excess cortisol secretion is probably the cause of the android features of obesity."}
{"id": "PMID:225219", "title": "[Mechanisms of spontaneous hypoglycaemia in the adult (author's transl)].", "content": "Hypoglycaemia increases hepatic glucose output; insulin release is suppressed and the secretion of counter regulatory hormones enhanced. Catecholamines and glucagon seem to play a major role. The brain energy content is initially preserved, but the neuronal activity exhibits a 40-60 % decrease. Neither cerebral blood flow, nor oxygen consumption are altered. In addition to glucose, other substrates are metabolized. Cerebral edema may occur. An insulin-storage defect seems to be the main abnormality in insulinoma beta cell function. The most accurate biological tests are the insulin/glucose ratio, stimulation tests and suppression tests such as fasting and insulin-induced hypoglycaemia. Ectopic release of ACTH, HCG, HLP, glucagon or gastrin, is observed in some malignant insulinomas. When inconclusive, classic localising procedures may be effected by selective venous-blood sampling. Hypoglycaemia of extra-pancreatic tumors results from glucose hyperconsumption and decreases in glucose hepatic output, lipolysis and ketogenesis, related to secretion of insulin-like peptides NSILAs or NSILAp. Rare cases of hypoglycaemia related to insulin auto-antibodies of unknown origin have been reported. Alcoholic hypoglycemia results from diminished hepatic glycogen content, alcohol dehydrogenase pathway blockade, reduction of gluconeogenesis defect in the alcohol catabolic catalase pathway and enhancement of peripheral glucose consumption.", "contents": "[Mechanisms of spontaneous hypoglycaemia in the adult (author's transl)]. Hypoglycaemia increases hepatic glucose output; insulin release is suppressed and the secretion of counter regulatory hormones enhanced. Catecholamines and glucagon seem to play a major role. The brain energy content is initially preserved, but the neuronal activity exhibits a 40-60 % decrease. Neither cerebral blood flow, nor oxygen consumption are altered. In addition to glucose, other substrates are metabolized. Cerebral edema may occur. An insulin-storage defect seems to be the main abnormality in insulinoma beta cell function. The most accurate biological tests are the insulin/glucose ratio, stimulation tests and suppression tests such as fasting and insulin-induced hypoglycaemia. Ectopic release of ACTH, HCG, HLP, glucagon or gastrin, is observed in some malignant insulinomas. When inconclusive, classic localising procedures may be effected by selective venous-blood sampling. Hypoglycaemia of extra-pancreatic tumors results from glucose hyperconsumption and decreases in glucose hepatic output, lipolysis and ketogenesis, related to secretion of insulin-like peptides NSILAs or NSILAp. Rare cases of hypoglycaemia related to insulin auto-antibodies of unknown origin have been reported. Alcoholic hypoglycemia results from diminished hepatic glycogen content, alcohol dehydrogenase pathway blockade, reduction of gluconeogenesis defect in the alcohol catabolic catalase pathway and enhancement of peripheral glucose consumption."}
{"id": "PMID:225233", "title": "Low density lipoprotein receptor activity in fibroblasts cultured from diabetic donors.", "content": "Low density lipoprotein (LDL) receptor activity was evaluated in cultured skin fibroblasts from diabetics and nondiabetic controls to evaluate whether intrinsic abnormalities of the LDL pathway exist, which might account for the premature atherosclerosis associated with diabetes mellitus. LDL receptors did not differ between cells grown from 16 diabetics (7 insulin-dependent, 9 non-insulin-dependent ) or from 16 nondiabetic controls. An inverse relationship between LDL receptor activity and cell density was observed (y = 1.35x-1.22, r = 0.90, P less than 0.001), which appeared the same for diabetic and nondiabetic cells. Normalized values for LDL degradation by diabetic and nondiabetic cell strains were 1.52 +/- 0.42% of added LDL/10(6) cells and 1.34 +/- 0.28, respectively (P = NS). The kinetics of the LDL receptor also appeared to be the same in cells derived from a diabetic and a nondiabetic donor. LDL receptor activity in diabetic cells increased appropriately in response to physiologic concentrations of insulin in the incubation mediu. Thus, LDL receptor activity appears to be normal in diabetic cell strains. Therefore, these results do not support the possibility that alterations in the LDL pathway contribute to the accelerated atherosclerosis associated with diabetes.", "contents": "Low density lipoprotein receptor activity in fibroblasts cultured from diabetic donors. Low density lipoprotein (LDL) receptor activity was evaluated in cultured skin fibroblasts from diabetics and nondiabetic controls to evaluate whether intrinsic abnormalities of the LDL pathway exist, which might account for the premature atherosclerosis associated with diabetes mellitus. LDL receptors did not differ between cells grown from 16 diabetics (7 insulin-dependent, 9 non-insulin-dependent ) or from 16 nondiabetic controls. An inverse relationship between LDL receptor activity and cell density was observed (y = 1.35x-1.22, r = 0.90, P less than 0.001), which appeared the same for diabetic and nondiabetic cells. Normalized values for LDL degradation by diabetic and nondiabetic cell strains were 1.52 +/- 0.42% of added LDL/10(6) cells and 1.34 +/- 0.28, respectively (P = NS). The kinetics of the LDL receptor also appeared to be the same in cells derived from a diabetic and a nondiabetic donor. LDL receptor activity in diabetic cells increased appropriately in response to physiologic concentrations of insulin in the incubation mediu. Thus, LDL receptor activity appears to be normal in diabetic cell strains. Therefore, these results do not support the possibility that alterations in the LDL pathway contribute to the accelerated atherosclerosis associated with diabetes."}
{"id": "PMID:225235", "title": "The prestalk-prespore pattern in cellular slime molds.", "content": "In cellular slime molds the slugs become divided into two regions with different properties, and anterior prestalk-zone and a posterior prespore zone. Although the cells in these zones are normally destined to form the stalk cells and spores of the fruiting body, respectively, they are not irreversibly committed to one sort of differentiation or the other during the slug stage. The volume ratio of the two zones remains almost constant over a wide range of slug sizes. If the prestalk-prespore pattern is distrubed by removing tissue from the slug, conversion of tissue from prestalk to prespore or vice versa occurs as necessary to restore a normal pattern with normal proportions. Conversions also occur in both directions during normal development. The initial formation of the prestalk-prespore pattern may well involve sorting-out, but other mechanisms must be invoked to account for regulation. We describe three different models of the generation of the prestalk-prespore pattern, the'cell-contact model' of McMahon, in which pattern is created by interactions of cells with their immediate neighbors, the 'positional-information model' of various authors, in which pattern formation involves an overall gradient and a gradient-reading mechanism, and the 'activator-inhibitor model' of Gierer and Meinhardt, in which the prestalk-prespore pattern is formed by a system of diffusible substances that affect one another's production. The activator-inhibitor model is the most successful of the models at describing the known features of the prestalk-prespore pattern. The various models lead to a number of distinctive predictions. According to the cell-contact model, small transplants may cause gross changes in the prestalk-prespore pattern, and mutants may exist which severely disrupt pattern formation even if diluted with a large excess of wild-type cells. Positional-information models predict the existence of 'gradient-reading mutants'; slugs that are a mixture of such mutants and wild-type cells would show two prestalk-prespore boundaries, one at the mutant and one at the normal position. Both the activator-inhibitor model and some versions of the positional-information model predict that small transplants will sometimes induce accessory prestalk or prespore zones; the quantitative characteristics of these effects may allow one to make a case in favor of one or other of the two models. Finally, the activator-inhibitor model leads one to expect that mutants may be isolated which normally show accessory prestalk or prespore zones. A search for these phenomena may help determine whether the activator-inhibitor model will continue to enjoy its present preeminent position.", "contents": "The prestalk-prespore pattern in cellular slime molds. In cellular slime molds the slugs become divided into two regions with different properties, and anterior prestalk-zone and a posterior prespore zone. Although the cells in these zones are normally destined to form the stalk cells and spores of the fruiting body, respectively, they are not irreversibly committed to one sort of differentiation or the other during the slug stage. The volume ratio of the two zones remains almost constant over a wide range of slug sizes. If the prestalk-prespore pattern is distrubed by removing tissue from the slug, conversion of tissue from prestalk to prespore or vice versa occurs as necessary to restore a normal pattern with normal proportions. Conversions also occur in both directions during normal development. The initial formation of the prestalk-prespore pattern may well involve sorting-out, but other mechanisms must be invoked to account for regulation. We describe three different models of the generation of the prestalk-prespore pattern, the'cell-contact model' of McMahon, in which pattern is created by interactions of cells with their immediate neighbors, the 'positional-information model' of various authors, in which pattern formation involves an overall gradient and a gradient-reading mechanism, and the 'activator-inhibitor model' of Gierer and Meinhardt, in which the prestalk-prespore pattern is formed by a system of diffusible substances that affect one another's production. The activator-inhibitor model is the most successful of the models at describing the known features of the prestalk-prespore pattern. The various models lead to a number of distinctive predictions. According to the cell-contact model, small transplants may cause gross changes in the prestalk-prespore pattern, and mutants may exist which severely disrupt pattern formation even if diluted with a large excess of wild-type cells. Positional-information models predict the existence of 'gradient-reading mutants'; slugs that are a mixture of such mutants and wild-type cells would show two prestalk-prespore boundaries, one at the mutant and one at the normal position. Both the activator-inhibitor model and some versions of the positional-information model predict that small transplants will sometimes induce accessory prestalk or prespore zones; the quantitative characteristics of these effects may allow one to make a case in favor of one or other of the two models. Finally, the activator-inhibitor model leads one to expect that mutants may be isolated which normally show accessory prestalk or prespore zones. A search for these phenomena may help determine whether the activator-inhibitor model will continue to enjoy its present preeminent position."}
{"id": "PMID:225236", "title": "Immunohistochemical localization of cyclic GMP in aggregating Polysphondylium violaceum.", "content": "Using indirect immunofluorescence technique, it has been possible to localize cyclic GMP in Polysphondylium violaceum cells. The bound cyclic nucleotide is localized throughout the cell during early stages, however, this staining increases and there is marked localization of cyclic GMP in the nuclear areas of the cells when aggregation is in full swing. Over 90% of the cells exhibited intense nuclear staining by 6 h and this decreased to less than 10% by 10 h.", "contents": "Immunohistochemical localization of cyclic GMP in aggregating Polysphondylium violaceum. Using indirect immunofluorescence technique, it has been possible to localize cyclic GMP in Polysphondylium violaceum cells. The bound cyclic nucleotide is localized throughout the cell during early stages, however, this staining increases and there is marked localization of cyclic GMP in the nuclear areas of the cells when aggregation is in full swing. Over 90% of the cells exhibited intense nuclear staining by 6 h and this decreased to less than 10% by 10 h."}
{"id": "PMID:225241", "title": "Persistence of phage lambda DNA in genomes of mouse cells transformed by lambda-carrying SV40 vectors.", "content": "To test the suitability of simian virus 40 (SV40) DNA as a vector for inserting DNA segments into the chromosomes of mammalian cells, an EcoRI-A fragment of bacteriophage lambda DNA was covalently joined to a fragment of SV40 DNA and used to transform mouse cells in culture. Three independent, morphologically transformed clones were obtained that were positive for SV40 T-antigen by immunofluorescence staining. DNA from each transformant was examined by restriction enzyme analysis and found to contain both lambda and SV40 sequences. Co-migration of some fragments containing lambda and SV40 sequences following digestion of transformed cell DNA by each of four different restriction enzymes indicated that part of the retained lambda and SV40 DNA was linked in two of the three lines. In the third line, however, none of the restriction fragments had both lambda and SV40 sequences. Although the presence of non-integrated lambda DNA was not excluded, at least some of the lambda DNA appeared to be linked to host cell DNA. Results of digestion by EcoRI suggested that in some cases the transforming linear molecule had probably circularized prior to integration.", "contents": "Persistence of phage lambda DNA in genomes of mouse cells transformed by lambda-carrying SV40 vectors. To test the suitability of simian virus 40 (SV40) DNA as a vector for inserting DNA segments into the chromosomes of mammalian cells, an EcoRI-A fragment of bacteriophage lambda DNA was covalently joined to a fragment of SV40 DNA and used to transform mouse cells in culture. Three independent, morphologically transformed clones were obtained that were positive for SV40 T-antigen by immunofluorescence staining. DNA from each transformant was examined by restriction enzyme analysis and found to contain both lambda and SV40 sequences. Co-migration of some fragments containing lambda and SV40 sequences following digestion of transformed cell DNA by each of four different restriction enzymes indicated that part of the retained lambda and SV40 DNA was linked in two of the three lines. In the third line, however, none of the restriction fragments had both lambda and SV40 sequences. Although the presence of non-integrated lambda DNA was not excluded, at least some of the lambda DNA appeared to be linked to host cell DNA. Results of digestion by EcoRI suggested that in some cases the transforming linear molecule had probably circularized prior to integration."}
{"id": "PMID:225244", "title": "An autopsy case of progressive dementia showing special intraplasmic inclusions in diffuse cerebral cortex.", "content": "A 29-year-old male characterized by progressive dementia has been described. Histopathologically, the changes obtained were as follows: 1) Some atrophic nerve cells contained homogeneous round or oval intraplasmic inclusions which could be stained with periodic acid-Schiff and coupled tetrazonium. From these examinations the inclusions consisted of neutral mucopolysaccharide including protein. 2) Mild neuronal loss was diffusely present. 3) Most of the remaining nerve cells were atrophic. The above-described findings were observed diffusely in the whole cortex of the brain. To our knowledge, the present case does not belong to the category of any well-known pathological diseases.", "contents": "An autopsy case of progressive dementia showing special intraplasmic inclusions in diffuse cerebral cortex. A 29-year-old male characterized by progressive dementia has been described. Histopathologically, the changes obtained were as follows: 1) Some atrophic nerve cells contained homogeneous round or oval intraplasmic inclusions which could be stained with periodic acid-Schiff and coupled tetrazonium. From these examinations the inclusions consisted of neutral mucopolysaccharide including protein. 2) Mild neuronal loss was diffusely present. 3) Most of the remaining nerve cells were atrophic. The above-described findings were observed diffusely in the whole cortex of the brain. To our knowledge, the present case does not belong to the category of any well-known pathological diseases."}
{"id": "PMID:225246", "title": "Percutaneous transhepatic portography in bile duct carcinoma. Correlation with percutaneous transhepatic cholangiography and angiography.", "content": "In 16 patients with carcinoma of the extrahepatic bile ducts, percutaneous transhepatic portography (PTP) and cholangiography (PTC) were performed. Fourteen of these patients also had angiography, which failed to show the tumor in 7 cases. Findings indicating non-extirpability of the tumor were demonstrated by angiography in 3 patients. At PTP non-extirpability was confirmed in these cases. PTP further indicated non-extirpability in one patient and gave hints of infiltration of the liver by the tumor in 5 patients because of intra or extrahepatic invasion of the portal vein.", "contents": "Percutaneous transhepatic portography in bile duct carcinoma. Correlation with percutaneous transhepatic cholangiography and angiography. In 16 patients with carcinoma of the extrahepatic bile ducts, percutaneous transhepatic portography (PTP) and cholangiography (PTC) were performed. Fourteen of these patients also had angiography, which failed to show the tumor in 7 cases. Findings indicating non-extirpability of the tumor were demonstrated by angiography in 3 patients. At PTP non-extirpability was confirmed in these cases. PTP further indicated non-extirpability in one patient and gave hints of infiltration of the liver by the tumor in 5 patients because of intra or extrahepatic invasion of the portal vein."}
{"id": "PMID:225247", "title": "[The radiologic diagnosis of inguinal hernias. Experience with the use of intraperitoneal iodinated contrast media (author's transl)].", "content": "By injecting an iodine contrast medium into the abdominal cavity and by placing the patient in a position with the table somewhat elevated, it is easy to visualize the inguinal region. The examination is performed with the X-ray tube angulated caudally, and exposures are made while the patient is straining. The method is well adapted for patients with obscure pains in the groins, for patients operated for hernias but not cured of pain and for patients in whom symptoms recur postoperatively without clinical evidence of hernial relapse. The value of the methode appears from four short case reports.", "contents": "[The radiologic diagnosis of inguinal hernias. Experience with the use of intraperitoneal iodinated contrast media (author's transl)]. By injecting an iodine contrast medium into the abdominal cavity and by placing the patient in a position with the table somewhat elevated, it is easy to visualize the inguinal region. The examination is performed with the X-ray tube angulated caudally, and exposures are made while the patient is straining. The method is well adapted for patients with obscure pains in the groins, for patients operated for hernias but not cured of pain and for patients in whom symptoms recur postoperatively without clinical evidence of hernial relapse. The value of the methode appears from four short case reports."}
{"id": "PMID:225252", "title": "Plasma lipids and high density lipoproteins during oral contraception with different combinations of ethinyl estradiol and levonorgestrel.", "content": "Seventy-five menstruating women seeking contraceptive advice were randomly allocated to treatment with combined oral contraceptives containing either ethinyl estradiol 50 micrograms + levonorgestrel 250 micrograms (50/250), ethinyl estradiol 30 micrograms + levonorgestrel 150 micrograms (30/150) or ethinyl estradiol 50 micrograms + levonorgestrel 125 micrograms (50/125). The concentrations of cholesterol, triglycerides, phospholipids, high density lipoprotein (HDL)-cholesterol and HDL-phospholipids were determined after one, three and six months and compared to the mean of two determinations of the same parameters before medication. Triglycerides increased by 18--42 per cent after 1--6 months of treatment with 50/125. The HDL-cholesterol and HDL-phospholipids were reduced by 10 per cent during 50/250 treatment. No other parameters showed any consistent alteration in any of the treatment groups. Raised triglyceride concentration and/or decreased HDL concentration increases the risk for cardiovascular disease. It is therefore suggested that in order not to alter the HDL concentration a combined oral contraceptive agent should not contain more gestagen-androgen than corresponding to 125--150 micrograms of levonorgestrel. To avoid a rise of the triglyceride level the weight relation between levonorgestrel and ethinyl estradiol should be about 5:1.", "contents": "Plasma lipids and high density lipoproteins during oral contraception with different combinations of ethinyl estradiol and levonorgestrel. Seventy-five menstruating women seeking contraceptive advice were randomly allocated to treatment with combined oral contraceptives containing either ethinyl estradiol 50 micrograms + levonorgestrel 250 micrograms (50/250), ethinyl estradiol 30 micrograms + levonorgestrel 150 micrograms (30/150) or ethinyl estradiol 50 micrograms + levonorgestrel 125 micrograms (50/125). The concentrations of cholesterol, triglycerides, phospholipids, high density lipoprotein (HDL)-cholesterol and HDL-phospholipids were determined after one, three and six months and compared to the mean of two determinations of the same parameters before medication. Triglycerides increased by 18--42 per cent after 1--6 months of treatment with 50/125. The HDL-cholesterol and HDL-phospholipids were reduced by 10 per cent during 50/250 treatment. No other parameters showed any consistent alteration in any of the treatment groups. Raised triglyceride concentration and/or decreased HDL concentration increases the risk for cardiovascular disease. It is therefore suggested that in order not to alter the HDL concentration a combined oral contraceptive agent should not contain more gestagen-androgen than corresponding to 125--150 micrograms of levonorgestrel. To avoid a rise of the triglyceride level the weight relation between levonorgestrel and ethinyl estradiol should be about 5:1."}
{"id": "PMID:225253", "title": "The effects of growth hormone, thyroxine and insulin on the activities of reduced nicotinamide adenine dinucleotide phosphate dehydrogenase, glucose-6-phosphatase and glycogen phosphorylase in fetal rat liver.", "content": "Growth hormone (GH), thyroxine (T4) and insulin were injected, in utero into 20.5 day-old rat fetuses to study the effects of these hormones on the activities of liver NADPH dehydrogenase, glucose-6-phosphatase and glycogen phosphorylase. It was found that at 21.5 days of gestation, GH increases the fetal liver glucose-6-phosphatase activity and decreases the liver glycogen phosphorylase activity. T4 treatment augments the activity of NADPH dehydrogenase even at 0.3% of the dose shown previously to produce premature elevation of activity. Prior to this experiment T4 in large doses has been shown to be capable of elevating glucose-6-phosphatase. However, at the lower T4 dose used, no treatment effect was observed. The fetal rat liver is responsive to insulin at 21.5 days and insulin was able to depress glucose-6-phosphatase activity. Thereby, showing that the influence of insulin on this enzyme begins prior to birth instead of just subsequent to birth.", "contents": "The effects of growth hormone, thyroxine and insulin on the activities of reduced nicotinamide adenine dinucleotide phosphate dehydrogenase, glucose-6-phosphatase and glycogen phosphorylase in fetal rat liver. Growth hormone (GH), thyroxine (T4) and insulin were injected, in utero into 20.5 day-old rat fetuses to study the effects of these hormones on the activities of liver NADPH dehydrogenase, glucose-6-phosphatase and glycogen phosphorylase. It was found that at 21.5 days of gestation, GH increases the fetal liver glucose-6-phosphatase activity and decreases the liver glycogen phosphorylase activity. T4 treatment augments the activity of NADPH dehydrogenase even at 0.3% of the dose shown previously to produce premature elevation of activity. Prior to this experiment T4 in large doses has been shown to be capable of elevating glucose-6-phosphatase. However, at the lower T4 dose used, no treatment effect was observed. The fetal rat liver is responsive to insulin at 21.5 days and insulin was able to depress glucose-6-phosphatase activity. Thereby, showing that the influence of insulin on this enzyme begins prior to birth instead of just subsequent to birth."}
{"id": "PMID:225254", "title": "Congenital hypoaldosteronism. Thirteen year follow-up in identical twins.", "content": "Identical male twins suffering from congenital hypoaldosteronism due to a rare adrenal enzyme deficiency between corticosterone and aldosterone were followed-upfrom birth till their present age of 13 years. The symptoms of salt loss disappeared and normal growth rate resumed following treatment with DOCA and salt supplementation. Discontinuation of mineralocorticoid administration at the age of 7 years resulted during a 5-year period in a marked decline in their growth rate. Labororatory data revealed a persistent, albeit less pronounced, metabolic impairment. Mineralocorticoid administration was resumed and the twins entered normal puberty and increased their growth rate, emphasizing their need for continued mineralocorticoid administration to maintain adequate growth rate and development.", "contents": "Congenital hypoaldosteronism. Thirteen year follow-up in identical twins. Identical male twins suffering from congenital hypoaldosteronism due to a rare adrenal enzyme deficiency between corticosterone and aldosterone were followed-upfrom birth till their present age of 13 years. The symptoms of salt loss disappeared and normal growth rate resumed following treatment with DOCA and salt supplementation. Discontinuation of mineralocorticoid administration at the age of 7 years resulted during a 5-year period in a marked decline in their growth rate. Labororatory data revealed a persistent, albeit less pronounced, metabolic impairment. Mineralocorticoid administration was resumed and the twins entered normal puberty and increased their growth rate, emphasizing their need for continued mineralocorticoid administration to maintain adequate growth rate and development."}
{"id": "PMID:225255", "title": "Reduced response of plasma aldosterone to acute ACTH stimulation during long-term treatment with spironolactone in essential hypertension.", "content": "The response of plasma aldosterone (PA) to ACTH administration (250 micrograms alpha 1-24 ACTH i.m.) before and during treatment with spironolactone (Sp, 75--100 mg/day) for at least 8 months was studied in 11 patients with essential hypertension. These responses were compared with those before and during prolonged treatment with hydrochlorothiazide (Th, 50--75 mg/day), with or without potassium supplement, in 14 hypertensives. PA and plasma cortisol (PC) were determined by radioimmunoassay in which Sp showed minimal cross-reactivity. Both Sp and Th treatments caused similar increases in plasma renin activity accompanied by nearly identical decreases in blood pressure and body weight. PA was also increased by both treatments, but to a significantly greater extent in the Sp-treated group. Serum potassium concentration was increased only by Sp treatment. The response of PA, but not of PC, to acute ACTH stimulation was blunted in the Sp-treated group. That is, the maximal increment of PA above the baseline level was significantly lower during Sp treatment than either before Sp treatment of during Th treatment. These results demonstrate that long-term treatment with Sp can inhibit aldosterone production by acute ACTH stimulation in patients with essential hypertension.", "contents": "Reduced response of plasma aldosterone to acute ACTH stimulation during long-term treatment with spironolactone in essential hypertension. The response of plasma aldosterone (PA) to ACTH administration (250 micrograms alpha 1-24 ACTH i.m.) before and during treatment with spironolactone (Sp, 75--100 mg/day) for at least 8 months was studied in 11 patients with essential hypertension. These responses were compared with those before and during prolonged treatment with hydrochlorothiazide (Th, 50--75 mg/day), with or without potassium supplement, in 14 hypertensives. PA and plasma cortisol (PC) were determined by radioimmunoassay in which Sp showed minimal cross-reactivity. Both Sp and Th treatments caused similar increases in plasma renin activity accompanied by nearly identical decreases in blood pressure and body weight. PA was also increased by both treatments, but to a significantly greater extent in the Sp-treated group. Serum potassium concentration was increased only by Sp treatment. The response of PA, but not of PC, to acute ACTH stimulation was blunted in the Sp-treated group. That is, the maximal increment of PA above the baseline level was significantly lower during Sp treatment than either before Sp treatment of during Th treatment. These results demonstrate that long-term treatment with Sp can inhibit aldosterone production by acute ACTH stimulation in patients with essential hypertension."}
{"id": "PMID:225256", "title": "Studies on the mode of action of gonadotrophin-inhibiting material (anti-LH) isolated from human urine.", "content": "Gonadotrophin-inhibiting material (GIM) was able to inhibit the binding of 125I-hCG to rat Leydig cells, suggesting that its inhibiting properties are due to its ability to complete for the hCG binding sites on Leydig cells. Binding of fluorescein isothiocyanate-tagged GIM to Leydig cells was also seen. The effect of GIM on hCG-induced adenylate cyclase activation and testosterone production was also studied. It was found that there was a dose-dependent inhibition of both these effects.", "contents": "Studies on the mode of action of gonadotrophin-inhibiting material (anti-LH) isolated from human urine. Gonadotrophin-inhibiting material (GIM) was able to inhibit the binding of 125I-hCG to rat Leydig cells, suggesting that its inhibiting properties are due to its ability to complete for the hCG binding sites on Leydig cells. Binding of fluorescein isothiocyanate-tagged GIM to Leydig cells was also seen. The effect of GIM on hCG-induced adenylate cyclase activation and testosterone production was also studied. It was found that there was a dose-dependent inhibition of both these effects."}
{"id": "PMID:225260", "title": "Characterization of cells cultured from early lactation milks.", "content": "Two major types of cells can be cultured from early lactation human milks: a colony-forming epithelial cell and an adherent nondividing cell referred to as a foam cell. The epithelial cells show a positive reaction with a specific antiserum reactive against membrane components of the milk fat globule, whereas the foam cells do not. The nondividing foam cells are phagocytic and can be killed by silica particles; they produce lysozyme, are resistant to trypsinization, and have Fc receptors. These properties, together with the lack of reaction with antiserum to the milk fat globule membrane, suggest that the foam cells are not terminally differentiated epithelial cells, but tissue macrophages.", "contents": "Characterization of cells cultured from early lactation milks. Two major types of cells can be cultured from early lactation human milks: a colony-forming epithelial cell and an adherent nondividing cell referred to as a foam cell. The epithelial cells show a positive reaction with a specific antiserum reactive against membrane components of the milk fat globule, whereas the foam cells do not. The nondividing foam cells are phagocytic and can be killed by silica particles; they produce lysozyme, are resistant to trypsinization, and have Fc receptors. These properties, together with the lack of reaction with antiserum to the milk fat globule membrane, suggest that the foam cells are not terminally differentiated epithelial cells, but tissue macrophages."}
{"id": "PMID:225261", "title": "Interferon production by mammalian cells grown in a serum-free medium.", "content": "Interferon, produced by rabbit heart cells grown in a serum-free medium, failed to protect rabbit heart serum-free cells, but protected rabbit heart serum-containing-medium cells against vaccinia and vesicular stomatitis virus. Interferon produced in serum-free cells had a greater species specificity than that produced in serum-containing media. The difference in activity was shown to be due to lack of adsorption by serum-free-medium cells.", "contents": "Interferon production by mammalian cells grown in a serum-free medium. Interferon, produced by rabbit heart cells grown in a serum-free medium, failed to protect rabbit heart serum-free cells, but protected rabbit heart serum-containing-medium cells against vaccinia and vesicular stomatitis virus. Interferon produced in serum-free cells had a greater species specificity than that produced in serum-containing media. The difference in activity was shown to be due to lack of adsorption by serum-free-medium cells."}
{"id": "PMID:225263", "title": "Collagen synthesis in normal BHK cells and temperature-sensitive chemically transformed BHK cells.", "content": "Collagen synthesis in normal BHK 21/cl 13 and chemically transformed temperature sensitive BHK 21/cl 13 cells (Me2N4) was assessed by examination of hydroxyproline formation and collagenase-susceptible protein. The Me2N4 cells lost their ability to synthesize collagen at both permissive and nonpermissive temperatures for transformation. These conclusions were confirmed by polyacrylamide-gel eletrophoresis and CM-cellulose chromatography. Prolyl hydroxylase activity was present in both normal and transformed cells even when no collagen could be demonstrated. The production of noncollagen protein, although decreased in the transformed cell, did not change as drastically as the collagen synthesis.", "contents": "Collagen synthesis in normal BHK cells and temperature-sensitive chemically transformed BHK cells. Collagen synthesis in normal BHK 21/cl 13 and chemically transformed temperature sensitive BHK 21/cl 13 cells (Me2N4) was assessed by examination of hydroxyproline formation and collagenase-susceptible protein. The Me2N4 cells lost their ability to synthesize collagen at both permissive and nonpermissive temperatures for transformation. These conclusions were confirmed by polyacrylamide-gel eletrophoresis and CM-cellulose chromatography. Prolyl hydroxylase activity was present in both normal and transformed cells even when no collagen could be demonstrated. The production of noncollagen protein, although decreased in the transformed cell, did not change as drastically as the collagen synthesis."}
{"id": "PMID:225265", "title": "Regulation of bradykinin-induced cyclic amp response by quinacrine and prostaglandin E2 and F2 alpha in human synovial fibroblasts.", "content": "Bradykinin induces an increment in intracellular cyclic AMP concentrations of human synovial fibroblasts and evokes the release of [3H]arachidonic acid and [3H]-E prostaglandins from human synovial fibroblasts pre-labeled in their phospholipids. Both these bradykinin-induced reactions are inhibited by quinacrine, an inhibitor of phospholipase A activity. The cyclic AMP response of human synovial fibroblasts to bradykinin is potentiated by prostaglandin E2 and inhibited by prostaglandin F2 alpha. These data emphasize the critical role of the prostaglandin system in reactions induced by bradykinin and suggest mechansims by which inflammatory reactions due to bradykinin may be modulated.", "contents": "Regulation of bradykinin-induced cyclic amp response by quinacrine and prostaglandin E2 and F2 alpha in human synovial fibroblasts. Bradykinin induces an increment in intracellular cyclic AMP concentrations of human synovial fibroblasts and evokes the release of [3H]arachidonic acid and [3H]-E prostaglandins from human synovial fibroblasts pre-labeled in their phospholipids. Both these bradykinin-induced reactions are inhibited by quinacrine, an inhibitor of phospholipase A activity. The cyclic AMP response of human synovial fibroblasts to bradykinin is potentiated by prostaglandin E2 and inhibited by prostaglandin F2 alpha. These data emphasize the critical role of the prostaglandin system in reactions induced by bradykinin and suggest mechansims by which inflammatory reactions due to bradykinin may be modulated."}
{"id": "PMID:225266", "title": "Unique characteristics of superoxide production by human eosinophils in eosinophilic states.", "content": "Eosinophils from patients with peripheral blood eosinophilia and human neutrophils from normal subjects and patients with neutrophilia produced superoxide anion (O2-) in vitro at similar rates in the absence of stimulation and exhibited comparably increased rates of O2- production during the initial 1 h of incubation with opsonized zymosan. In the presence of opsonized zymosan, the rate of O2- production by eosinophils was constantly high for 3 h, whereas the rate of production by neutrophils fell by more than 65% after 1 h. Consequently, the amount of superoxide produced by phagocytizing leukocytes was twofold higher for eosinophils than for neutrophils at 3 h. O2- production by cell-free sonicates of zymosan-stimulated eosinophils and neutrophils exhibited the same preference for NADPH over NADH. One mM sodium azide significantly decreased the generation of O2- by phagocytizing eosinophils, but lacked an effect on neutrophils. the prolonged release of O2- by eosinophils engaged in phagocytosis may contribute both to their unique microbicidal profile and to the capacity of eosinophils to injure host tissues in some eosinophilic syndromes.", "contents": "Unique characteristics of superoxide production by human eosinophils in eosinophilic states. Eosinophils from patients with peripheral blood eosinophilia and human neutrophils from normal subjects and patients with neutrophilia produced superoxide anion (O2-) in vitro at similar rates in the absence of stimulation and exhibited comparably increased rates of O2- production during the initial 1 h of incubation with opsonized zymosan. In the presence of opsonized zymosan, the rate of O2- production by eosinophils was constantly high for 3 h, whereas the rate of production by neutrophils fell by more than 65% after 1 h. Consequently, the amount of superoxide produced by phagocytizing leukocytes was twofold higher for eosinophils than for neutrophils at 3 h. O2- production by cell-free sonicates of zymosan-stimulated eosinophils and neutrophils exhibited the same preference for NADPH over NADH. One mM sodium azide significantly decreased the generation of O2- by phagocytizing eosinophils, but lacked an effect on neutrophils. the prolonged release of O2- by eosinophils engaged in phagocytosis may contribute both to their unique microbicidal profile and to the capacity of eosinophils to injure host tissues in some eosinophilic syndromes."}
{"id": "PMID:225267", "title": "Tobacco smoke. Effects on pulmonary host defense.", "content": "Tobacco smoke affected both the metabolism and function of pulmonary alveolar macrophages (PAM). Phagocytosis of viable Staphylococcus aureus and inert starch particles was minimally but consistently depressed in PAM from rats exposed to tobacco smoke for six months. Oxygen consumption, superoxide and hydrogen peroxide release, and hexose monophosphate shunt activity were elevated in cells from smokers. Oxidation of glucose, labelled in the carbon-six position, remained unchanged. All observed effects of tobacco smoke on oxygen metabolism occurred during phagocytosis and did not affect the basal metabolism of the nonstimulated cell.", "contents": "Tobacco smoke. Effects on pulmonary host defense. Tobacco smoke affected both the metabolism and function of pulmonary alveolar macrophages (PAM). Phagocytosis of viable Staphylococcus aureus and inert starch particles was minimally but consistently depressed in PAM from rats exposed to tobacco smoke for six months. Oxygen consumption, superoxide and hydrogen peroxide release, and hexose monophosphate shunt activity were elevated in cells from smokers. Oxidation of glucose, labelled in the carbon-six position, remained unchanged. All observed effects of tobacco smoke on oxygen metabolism occurred during phagocytosis and did not affect the basal metabolism of the nonstimulated cell."}
{"id": "PMID:225268", "title": "Effect of estrogens on the myeloperoxidase-mediated antimicrobial system.", "content": "Estradiol 17 beta prevented the fall in the microbicidal activity of the myeloperoxidase-H2O2-halide system induced by high H2O2 concentrations. In contrast, when the H2O2 (and halide) concentrations were low the myeloperoxidase-H2O2-halide antimicrobial system was inhibited by estradiol. These properties of estradiol 17 beta were shared by estradiol 17 alpha, estrone, estriol, ethinyl estradiol, and phenol, but not by estradiol-3-benzoate, testosterone, progesterone, hydroxyprogesterone, cortisone, hydrocortisone, or deoxycorticosterone.", "contents": "Effect of estrogens on the myeloperoxidase-mediated antimicrobial system. Estradiol 17 beta prevented the fall in the microbicidal activity of the myeloperoxidase-H2O2-halide system induced by high H2O2 concentrations. In contrast, when the H2O2 (and halide) concentrations were low the myeloperoxidase-H2O2-halide antimicrobial system was inhibited by estradiol. These properties of estradiol 17 beta were shared by estradiol 17 alpha, estrone, estriol, ethinyl estradiol, and phenol, but not by estradiol-3-benzoate, testosterone, progesterone, hydroxyprogesterone, cortisone, hydrocortisone, or deoxycorticosterone."}
{"id": "PMID:225269", "title": "Cell-mediated immunity to varicella-zoster virus measured by virus inactivation: mechanism and blocking of the reaction by specific antibody.", "content": "The process whereby varicella-zoster (V-Z) virus is inactivated in vitro by immune human peripheral blood leukocytes stimulated with V-Z antigen was examined. It was found that stimulation of leukocytes by V-Z antigen, but not by other viral antigens, was required for inactivation of V-Z virus to occur. Viral inactivation could be blocked by addition of V-Z antiserum to either the stimulation phase of the reaction or the inactivation phase, further demonstrating the specificity of the reaction. In addition these blocking experiments suggested that modulation of V-Z membrane antigen by antiserum occurred with an accompanying loss of immunological recognition of virus-infected cells. Inactivation of V-Z virus in vitro in this study appeared not to be dependent upon the secretion of interferon or upon antibody-dependent cellular cytotoxicity. The specific cells required for V-Z inactivation were T lymphocytes and monocytes (macrophage precursors).", "contents": "Cell-mediated immunity to varicella-zoster virus measured by virus inactivation: mechanism and blocking of the reaction by specific antibody. The process whereby varicella-zoster (V-Z) virus is inactivated in vitro by immune human peripheral blood leukocytes stimulated with V-Z antigen was examined. It was found that stimulation of leukocytes by V-Z antigen, but not by other viral antigens, was required for inactivation of V-Z virus to occur. Viral inactivation could be blocked by addition of V-Z antiserum to either the stimulation phase of the reaction or the inactivation phase, further demonstrating the specificity of the reaction. In addition these blocking experiments suggested that modulation of V-Z membrane antigen by antiserum occurred with an accompanying loss of immunological recognition of virus-infected cells. Inactivation of V-Z virus in vitro in this study appeared not to be dependent upon the secretion of interferon or upon antibody-dependent cellular cytotoxicity. The specific cells required for V-Z inactivation were T lymphocytes and monocytes (macrophage precursors)."}
{"id": "PMID:225270", "title": "Cellular and humoral immune responses to varicella-zoster virus in immunocompromised patients during and after varicella-zoster infections.", "content": "Humoral and cell-mediated immune responses to varicella-zoster (V-Z) virus were assessed in patients during and after V-Z infections. Ongoing V-Z infections was associated with minimal cellular immunity but not necessarily with poor humoral immunity. Recovery from V-Z infection was associated with a vigorous cellular immune response. Cell-mediated immunity to V-Z virus was demonstrable for years after varicella, but responses were lower in immunocompromised patients than in normal individuals.", "contents": "Cellular and humoral immune responses to varicella-zoster virus in immunocompromised patients during and after varicella-zoster infections. Humoral and cell-mediated immune responses to varicella-zoster (V-Z) virus were assessed in patients during and after V-Z infections. Ongoing V-Z infections was associated with minimal cellular immunity but not necessarily with poor humoral immunity. Recovery from V-Z infection was associated with a vigorous cellular immune response. Cell-mediated immunity to V-Z virus was demonstrable for years after varicella, but responses were lower in immunocompromised patients than in normal individuals."}
{"id": "PMID:225271", "title": "Inhibition by cholera toxin of rat polymorphonuclear leukocyte chemotaxis demonstrated in vitro and in vivo.", "content": "The effect of cholera toxin on the chemotaxis of rat polymorphonuclear leukocytes (PMN) was studied using a technique in which the movement of the cells towards a laser-lysed erythrocyte is followed under a phase-contrast microscrope. In vitro studies indicated that the intact toxin was capable of inhibiting PMN chemotaxis in a dose-dependent manner at doses ranging from 1 to 100 ng/ml. Subunits A and B of the toxin were without inhibitory activity when used alone, but after recombination their ability to inhibit chemotaxis was similar to that of the intact toxin, suggesting that the toxin is acting intracellularly. Cholera toxin has been reported to act in other systems via stimulation of adenyl cyclase with consequent elevation of intracellular cyclic adenosine 5'-monophosphate (cAMP) levels. It appears that this mechanism may also account for its ability to inhibit chemotaxis since there was a correlation, at all doses tested, between inhibition of chemotaxis and increased intracellular cAMP levels. Cholera toxin was also found to be active in vivo in that, after intrapleural injection of the toxin, the chemotaxis of cells subsequently recovered from the pleural cavity was markedly reduced. These results support previous findings which suggest that modification of leukocyte cAMP levels can influence the chemotactic responsiveness of these cells.", "contents": "Inhibition by cholera toxin of rat polymorphonuclear leukocyte chemotaxis demonstrated in vitro and in vivo. The effect of cholera toxin on the chemotaxis of rat polymorphonuclear leukocytes (PMN) was studied using a technique in which the movement of the cells towards a laser-lysed erythrocyte is followed under a phase-contrast microscrope. In vitro studies indicated that the intact toxin was capable of inhibiting PMN chemotaxis in a dose-dependent manner at doses ranging from 1 to 100 ng/ml. Subunits A and B of the toxin were without inhibitory activity when used alone, but after recombination their ability to inhibit chemotaxis was similar to that of the intact toxin, suggesting that the toxin is acting intracellularly. Cholera toxin has been reported to act in other systems via stimulation of adenyl cyclase with consequent elevation of intracellular cyclic adenosine 5'-monophosphate (cAMP) levels. It appears that this mechanism may also account for its ability to inhibit chemotaxis since there was a correlation, at all doses tested, between inhibition of chemotaxis and increased intracellular cAMP levels. Cholera toxin was also found to be active in vivo in that, after intrapleural injection of the toxin, the chemotaxis of cells subsequently recovered from the pleural cavity was markedly reduced. These results support previous findings which suggest that modification of leukocyte cAMP levels can influence the chemotactic responsiveness of these cells."}
{"id": "PMID:225272", "title": "Antibody responses and interferon titers in the respiratory tracts of mice after aerosolized exposure to influenza virus.", "content": "We studied the temporal appearance of immunoglobulins (immunoglobulins G1, G2, M, and A) and interferon in lung lavage fluids of mice after aerosol exposure to influenza virus in six animal groups in which mortality rates ranged from 0 to 24%. Immunoglobulin levels in the lung lavage fluids were markedly higher in mouse groups with higher mortality rates (16, 20, and 24%) than in those with low mortality rates (0, 2.5, and 7.5%). Analysis of serum albumin in the respiratory secretions as an index of edema indicated that increased immunoglobulin G levels during the early phase of infection were due to increased vascular permeability. The detection of virus-neutralizing antibodies and antibodies reactive with influenza virus antigens in the lavage fluids at 6 to 8 days postinfection suggested local immunoglobulin synthesis as a result of antigenic stimulation. Both systemic and local antibody productions contributed to immunoglobulin levels in the respiratory secretions after aerosolized influenza virus infection. Peak levels of interferon in the lavage fluids were reached before detection of significant levels of virus-neutralizing antibody in the serum or the lung lavage.", "contents": "Antibody responses and interferon titers in the respiratory tracts of mice after aerosolized exposure to influenza virus. We studied the temporal appearance of immunoglobulins (immunoglobulins G1, G2, M, and A) and interferon in lung lavage fluids of mice after aerosol exposure to influenza virus in six animal groups in which mortality rates ranged from 0 to 24%. Immunoglobulin levels in the lung lavage fluids were markedly higher in mouse groups with higher mortality rates (16, 20, and 24%) than in those with low mortality rates (0, 2.5, and 7.5%). Analysis of serum albumin in the respiratory secretions as an index of edema indicated that increased immunoglobulin G levels during the early phase of infection were due to increased vascular permeability. The detection of virus-neutralizing antibodies and antibodies reactive with influenza virus antigens in the lavage fluids at 6 to 8 days postinfection suggested local immunoglobulin synthesis as a result of antigenic stimulation. Both systemic and local antibody productions contributed to immunoglobulin levels in the respiratory secretions after aerosolized influenza virus infection. Peak levels of interferon in the lavage fluids were reached before detection of significant levels of virus-neutralizing antibody in the serum or the lung lavage."}
{"id": "PMID:225273", "title": "Replication of vesicular stomatitis virus facilitated by Shope fibroma virus in vivo.", "content": "Previous studies show that Shope fibroma virus facilitates replication of vesicular stomatitis virus (VSV) in some rabbit cells grown in vitro. In the present investigation, the possibility that these two viruses can also interact in vivo was determined. Rabbits inoculated intradermally with both viruses together, or each separately, were examined for the formation of lesions or tumors and for the production of infectious virus. The presence of VSV interfered with tumorigenesis by Shope fibroma virus. In tumors already formed, production of infectious VSV was greater than in normal skin. Hence, each virus affected the other. Sera and tissues of normal rabbits were found to contain a substance which inhibits VSV; this may act to limit replication of VSV in rabbit skin. In addition, cultured rabbit skin cells appeared to adsorb VSV inefficiently. When persistently infected by Shope fibroma virus, however, adsorption of VSV was markedly improved. Our results suggest that in vivo Shope fibroma virus may facilitate adsorption of VSV to reduce the effect of a natural inhibitor and consequently enhance production of infectious virus.", "contents": "Replication of vesicular stomatitis virus facilitated by Shope fibroma virus in vivo. Previous studies show that Shope fibroma virus facilitates replication of vesicular stomatitis virus (VSV) in some rabbit cells grown in vitro. In the present investigation, the possibility that these two viruses can also interact in vivo was determined. Rabbits inoculated intradermally with both viruses together, or each separately, were examined for the formation of lesions or tumors and for the production of infectious virus. The presence of VSV interfered with tumorigenesis by Shope fibroma virus. In tumors already formed, production of infectious VSV was greater than in normal skin. Hence, each virus affected the other. Sera and tissues of normal rabbits were found to contain a substance which inhibits VSV; this may act to limit replication of VSV in rabbit skin. In addition, cultured rabbit skin cells appeared to adsorb VSV inefficiently. When persistently infected by Shope fibroma virus, however, adsorption of VSV was markedly improved. Our results suggest that in vivo Shope fibroma virus may facilitate adsorption of VSV to reduce the effect of a natural inhibitor and consequently enhance production of infectious virus."}
{"id": "PMID:225274", "title": "Metabolic and functional characteristics of alveolar macrophages recovered from rats exposed to marijuana smoke.", "content": "Pulmonary alveolar macrophages were obtained by bronchopulmonary lavage from male rats after 30 consecutive days of in vivo exposure to marijuana and tobacco smoke. No significant differences were found between either group of experimental animals and controls in the number of cells recovered, the protein content per 10(6) cells, or the percentage of cells that adhered to plastic surfaces. The ability of macrophages to phagocytize viable bacteria was not affected by exposure to either marijuana or tobacco smoke in that both treatment groups ingested Staphylococcus aureus over a 60-min period as well as did control cells. Differences were found between the groups, however, with respect to cellular metabolism. Marijuana smoke inhalation caused a small decrease in the amount of oxygen consumed by macrophages during phagocytosis, as compared with control cells. This may have been reflected in the even greater decrease in superoxide formation observed during particle engulfment by these treated cells. Tobacco smoke, on the other hand, increased oxygen consumption and was without effect on superoxide release. Neither tobacco nor marijuana smoke treatment had an effect on the direct oxidation of glucose via the hexose monophosphate shunt. Our results indicate that, despite several metabolic alterations in response to marijuana and tobacco smoke, alveolar macrophages were not compromised with respect to their ability to ingest a particulate challenge.", "contents": "Metabolic and functional characteristics of alveolar macrophages recovered from rats exposed to marijuana smoke. Pulmonary alveolar macrophages were obtained by bronchopulmonary lavage from male rats after 30 consecutive days of in vivo exposure to marijuana and tobacco smoke. No significant differences were found between either group of experimental animals and controls in the number of cells recovered, the protein content per 10(6) cells, or the percentage of cells that adhered to plastic surfaces. The ability of macrophages to phagocytize viable bacteria was not affected by exposure to either marijuana or tobacco smoke in that both treatment groups ingested Staphylococcus aureus over a 60-min period as well as did control cells. Differences were found between the groups, however, with respect to cellular metabolism. Marijuana smoke inhalation caused a small decrease in the amount of oxygen consumed by macrophages during phagocytosis, as compared with control cells. This may have been reflected in the even greater decrease in superoxide formation observed during particle engulfment by these treated cells. Tobacco smoke, on the other hand, increased oxygen consumption and was without effect on superoxide release. Neither tobacco nor marijuana smoke treatment had an effect on the direct oxidation of glucose via the hexose monophosphate shunt. Our results indicate that, despite several metabolic alterations in response to marijuana and tobacco smoke, alveolar macrophages were not compromised with respect to their ability to ingest a particulate challenge."}
{"id": "PMID:225275", "title": "Cytokine production by blue tongue virus-infected fetal sheep cells.", "content": "The migration inhibition of guinea pig peritoneal macrophages by a factor(s) from media obtained from blue tongue virus-infected monolayer cultures was studied. Medium from blue tongue virus-infected sheep fetal cell cultures inhibited migration of guinea pig macrophages from agarose droplets. Medium from control cultures and stock virus did not inhibit macrophage migration. Medium containing migration inhibiting factor(s) in vitro induced an inflammatory reaction in the skin of a newborn sheep. The inflammatory reaction was observed 20 h after intradermal inoculation. The skin reaction consisted of infiltrates of mononuclear leukocytes in the superficial dermis. Control medium and stock virus caused no skin reaction.", "contents": "Cytokine production by blue tongue virus-infected fetal sheep cells. The migration inhibition of guinea pig peritoneal macrophages by a factor(s) from media obtained from blue tongue virus-infected monolayer cultures was studied. Medium from blue tongue virus-infected sheep fetal cell cultures inhibited migration of guinea pig macrophages from agarose droplets. Medium from control cultures and stock virus did not inhibit macrophage migration. Medium containing migration inhibiting factor(s) in vitro induced an inflammatory reaction in the skin of a newborn sheep. The inflammatory reaction was observed 20 h after intradermal inoculation. The skin reaction consisted of infiltrates of mononuclear leukocytes in the superficial dermis. Control medium and stock virus caused no skin reaction."}
{"id": "PMID:225276", "title": "Enhancement of granulocyte chemiluminescence with hydroxyl radical scavengers.", "content": "Addition of hydroxyl radical scavengers (benzoate, ethanol, and mannitol) to granulocyte chemiluminescent reactions significantly enhanced light generation without altering granulocyte oxygen consumption or superoxide production.", "contents": "Enhancement of granulocyte chemiluminescence with hydroxyl radical scavengers. Addition of hydroxyl radical scavengers (benzoate, ethanol, and mannitol) to granulocyte chemiluminescent reactions significantly enhanced light generation without altering granulocyte oxygen consumption or superoxide production."}
{"id": "PMID:225277", "title": "Induction of virus-neutralizing antibody by glycoproteins isolated from chicken cells infected with a herpesvirus of turkeys.", "content": "The production of virus-induced proteins in chicken embryo fibroblast cells infected with a herpesvirus of turkeys was studied. It was found that glycoproteins isolated from membrane-rich fractions of infected cells by affinity chromatography using concanavalin A induced neutralizing and precipitating antibody in rabbits and chickens. After analytical electrophoresis, such isolates were found to contain three polypeptide bands of between 100 x 10(3) and 120 x 10(3) molecular weight not present in glycoprotein extracts of uninfected cells, and these polypeptides were further purified by preparative polyacrylamide gel electrophoresis. Inoculation of chickens with purified material also resulted in the production of precipitating and neutralizing antibody, showing that these high-molecular-weight polypeptides play a role in the humoral immunity to Marek's disease. Challenge of these chickens with virulent Marek's disease virus revealed that a partial protection was afforded by the inoculated glycoproteins.", "contents": "Induction of virus-neutralizing antibody by glycoproteins isolated from chicken cells infected with a herpesvirus of turkeys. The production of virus-induced proteins in chicken embryo fibroblast cells infected with a herpesvirus of turkeys was studied. It was found that glycoproteins isolated from membrane-rich fractions of infected cells by affinity chromatography using concanavalin A induced neutralizing and precipitating antibody in rabbits and chickens. After analytical electrophoresis, such isolates were found to contain three polypeptide bands of between 100 x 10(3) and 120 x 10(3) molecular weight not present in glycoprotein extracts of uninfected cells, and these polypeptides were further purified by preparative polyacrylamide gel electrophoresis. Inoculation of chickens with purified material also resulted in the production of precipitating and neutralizing antibody, showing that these high-molecular-weight polypeptides play a role in the humoral immunity to Marek's disease. Challenge of these chickens with virulent Marek's disease virus revealed that a partial protection was afforded by the inoculated glycoproteins."}
{"id": "PMID:225278", "title": "Serological response of the bovine fetus to bovine viral diarrhea virus.", "content": "Susceptible pregnant heifers were inoculated with bovine viral diarrhea virus at 150 days of gestation and earlier. Fetuses were surgically collected at selected times after inoculation. Serum immunoglobulins were quantitated, and the presence of specific antibodies was determined. In fetuses from heifers inoculated at 150 days, immunoglobulin M (IgM) appeared approximately 2 weeks after inoculation and was followed in 7 days by IgG1. Later IgG2 was detected in the sera of three fetuses. Serum-neutralizing and complement-fixing antibodies were first detected in a fetus taken at 206 days of gestation. Fetuses taken at later times also had specific serum antibodies. Possible explanations for the appearance of serum immunoglobulin substantially before specific bovine viral diarrhea antibodies include the viral alteration of host tissues rendering them antigenic viral activation of polyclonal B cells, and viral modulation of virus-specific lymphocytes causing specific interference with the appearance of antiviral antibodies. In one of the fetuses having IgG2, the serum also contained IgA. Placental leakage of material immunoglobulins was thought to be responsible for the presence of IgA and IgG2 in this fetus. Small quantities of IgM were found in the serum of two fetuses taken from heifers inoculated between 65 and 95 days of gestation, but specific antibodies were found in none.", "contents": "Serological response of the bovine fetus to bovine viral diarrhea virus. Susceptible pregnant heifers were inoculated with bovine viral diarrhea virus at 150 days of gestation and earlier. Fetuses were surgically collected at selected times after inoculation. Serum immunoglobulins were quantitated, and the presence of specific antibodies was determined. In fetuses from heifers inoculated at 150 days, immunoglobulin M (IgM) appeared approximately 2 weeks after inoculation and was followed in 7 days by IgG1. Later IgG2 was detected in the sera of three fetuses. Serum-neutralizing and complement-fixing antibodies were first detected in a fetus taken at 206 days of gestation. Fetuses taken at later times also had specific serum antibodies. Possible explanations for the appearance of serum immunoglobulin substantially before specific bovine viral diarrhea antibodies include the viral alteration of host tissues rendering them antigenic viral activation of polyclonal B cells, and viral modulation of virus-specific lymphocytes causing specific interference with the appearance of antiviral antibodies. In one of the fetuses having IgG2, the serum also contained IgA. Placental leakage of material immunoglobulins was thought to be responsible for the presence of IgA and IgG2 in this fetus. Small quantities of IgM were found in the serum of two fetuses taken from heifers inoculated between 65 and 95 days of gestation, but specific antibodies were found in none."}
{"id": "PMID:225281", "title": "Elevated titer of antibodies to Simian sarcoma virus envelope antigen (gp70) and normal response to influenza virus in untreated Danish Hodgkin's patients.", "content": "Untreated Danish Hodgkin's disease (HD) patients and paired age- and sex-matched controls were tested for serum antibodies to Epstein-Barr virus (EBV), six strains of influenza virus and Simian sarcoma virus/Simian sarcoma-associated virus [SSV(SSAV)] antigens. HD sera showed significantly elevated titers against EBV and both increased incidence and mean titer of antibodies to the envelope glycoprotein of SSV(SSAV), whereas testing against the influenza viruses revealed no differences between HD and controls. A focus reduction assay demonstrated a low incidence in HD and controls of sera with neutralizing effects against SSV(SSAV) and the \"baboon\" C-type virus component of the human HL-23 virus complex, which seemed coupled to HL-A type W19.", "contents": "Elevated titer of antibodies to Simian sarcoma virus envelope antigen (gp70) and normal response to influenza virus in untreated Danish Hodgkin's patients. Untreated Danish Hodgkin's disease (HD) patients and paired age- and sex-matched controls were tested for serum antibodies to Epstein-Barr virus (EBV), six strains of influenza virus and Simian sarcoma virus/Simian sarcoma-associated virus [SSV(SSAV)] antigens. HD sera showed significantly elevated titers against EBV and both increased incidence and mean titer of antibodies to the envelope glycoprotein of SSV(SSAV), whereas testing against the influenza viruses revealed no differences between HD and controls. A focus reduction assay demonstrated a low incidence in HD and controls of sera with neutralizing effects against SSV(SSAV) and the \"baboon\" C-type virus component of the human HL-23 virus complex, which seemed coupled to HL-A type W19."}
{"id": "PMID:225282", "title": "Growth of diploid, Epstein-Barr virus-carrying human lymphoblastoid cell lines heterotransplanted into nude mice under immunologically privileged conditions.", "content": "Human Epstein-Barr virus-carrying lymphoid cell lines which have been classified on the basis of studies on clonality and morphological, chromosomal and functional parameters as lymphoblastoid cell lines (LCL) of presumed non-neoplastic origin were inoculated intracerebrally into nude mice. All eighteen of them grew, killing the host mice within 7 to 25 days, except for 2 which grew more slowly. At autopsy, the brain of the nudes was found to be invaded by infiltrating lymphomas. Sixteen of these lymphomas, when recultured in vitro, gave rise to cell lines with growth properties and morphology indistinguishable from those of the inoculated LCL. Chromosomal examinations showed that 3/7 cell lines injected, which grew as lymphomas in the brain, were still normal diploid on reexplantation whereas the remaining four had become aneuploid. Four lines derived from intracerebral lymphomas (2 diploid, 1 aneuploid and 1 untested) were inoculated subcutaneously into adult nude mice. None of them grew. When the corresponding four original LCL lines were inoculated subcutaneously into newborn nude mice, they grew rapidly, but failed to do so in newborn normal mice or intracerebrally in adult normal mice. One such line, U-1450, was treated with anti-lymphocyte serum (ALS). Small nodules developed at the site of inoculation. From one nodule a cell line was cultured, 1450 ALSAD. It was morphologically indistinguishable from the line of origin. The lines obtained from nude mice inoculated with polyclonal LCL seem to have a restricted clonal representation, but were not monoclonal, as evidenced by analyses of their pattern of immunoglobulin synthesis.", "contents": "Growth of diploid, Epstein-Barr virus-carrying human lymphoblastoid cell lines heterotransplanted into nude mice under immunologically privileged conditions. Human Epstein-Barr virus-carrying lymphoid cell lines which have been classified on the basis of studies on clonality and morphological, chromosomal and functional parameters as lymphoblastoid cell lines (LCL) of presumed non-neoplastic origin were inoculated intracerebrally into nude mice. All eighteen of them grew, killing the host mice within 7 to 25 days, except for 2 which grew more slowly. At autopsy, the brain of the nudes was found to be invaded by infiltrating lymphomas. Sixteen of these lymphomas, when recultured in vitro, gave rise to cell lines with growth properties and morphology indistinguishable from those of the inoculated LCL. Chromosomal examinations showed that 3/7 cell lines injected, which grew as lymphomas in the brain, were still normal diploid on reexplantation whereas the remaining four had become aneuploid. Four lines derived from intracerebral lymphomas (2 diploid, 1 aneuploid and 1 untested) were inoculated subcutaneously into adult nude mice. None of them grew. When the corresponding four original LCL lines were inoculated subcutaneously into newborn nude mice, they grew rapidly, but failed to do so in newborn normal mice or intracerebrally in adult normal mice. One such line, U-1450, was treated with anti-lymphocyte serum (ALS). Small nodules developed at the site of inoculation. From one nodule a cell line was cultured, 1450 ALSAD. It was morphologically indistinguishable from the line of origin. The lines obtained from nude mice inoculated with polyclonal LCL seem to have a restricted clonal representation, but were not monoclonal, as evidenced by analyses of their pattern of immunoglobulin synthesis."}
{"id": "PMID:225286", "title": "Vascular basophilia in ocular and orbital tumors.", "content": "The occurrence of vascular basophilia in ocular tumors has been a selective histologic feature of retinoblastomas. We recently observed a metastatic oat-cell carcinoma to the choroid which also demonstrated such a vascular hematoxyphilia. Histologic review of a variety of ocular and orbital metastatic carcinomas failed to yield a similar basophilic pattern. Examination of 100 consecutive retinoblastomas for vascular basophilia revealed an incidence of 6.0%. Similar material was not seen in any of 125 melanomas, including 10 with areas of necrosis. Histochemical studies showed the basophilic material to be DNA, and electron microscopy revealed the nuclear debris of pyknotic tumor cells to be continuous with identical material surrounding the adjacent blood vessels. The pathogenesis of vascular deposition of DNA in these two ocular tumors remains unclear. This finding most likely represents a form of tumor activity requiring comparatively healthy blood vessels to adequately precipitate liberated nucleic acids being filtered from the necrotic and degenerating tumor tissue.", "contents": "Vascular basophilia in ocular and orbital tumors. The occurrence of vascular basophilia in ocular tumors has been a selective histologic feature of retinoblastomas. We recently observed a metastatic oat-cell carcinoma to the choroid which also demonstrated such a vascular hematoxyphilia. Histologic review of a variety of ocular and orbital metastatic carcinomas failed to yield a similar basophilic pattern. Examination of 100 consecutive retinoblastomas for vascular basophilia revealed an incidence of 6.0%. Similar material was not seen in any of 125 melanomas, including 10 with areas of necrosis. Histochemical studies showed the basophilic material to be DNA, and electron microscopy revealed the nuclear debris of pyknotic tumor cells to be continuous with identical material surrounding the adjacent blood vessels. The pathogenesis of vascular deposition of DNA in these two ocular tumors remains unclear. This finding most likely represents a form of tumor activity requiring comparatively healthy blood vessels to adequately precipitate liberated nucleic acids being filtered from the necrotic and degenerating tumor tissue."}
{"id": "PMID:225288", "title": "Adenovirus types 8 and 19 infection of rabbit corneal organ cultures.", "content": "Adenovirus types 8 and 19 are responsible for a large number of cases of acute follicular conjunctivitis, mainly in the form of epidemic keratoconjunctivitis (EKC). This study successfully demonstrates the establishment of adenovirus infection in rabbit corneal organ cultures. Normal rabbit corneas were maintained in culture without significant morphologic alterations for up to 7 weeks. Adenovirus types 8 and 19 replication in rabbit corneas was demonstrated by viral growth curves and subpassage studies. Intracellular localization of adenoviral antigens was confirmed with immunofluorescent techniques. The characteristic cytopathic effects of adenoviral infection were observed with the use of various histochemical stains. Thus an in vitro corneal organ culture model was established for the study of the pathogenesis of corneal lesions in adenovirus EKC.", "contents": "Adenovirus types 8 and 19 infection of rabbit corneal organ cultures. Adenovirus types 8 and 19 are responsible for a large number of cases of acute follicular conjunctivitis, mainly in the form of epidemic keratoconjunctivitis (EKC). This study successfully demonstrates the establishment of adenovirus infection in rabbit corneal organ cultures. Normal rabbit corneas were maintained in culture without significant morphologic alterations for up to 7 weeks. Adenovirus types 8 and 19 replication in rabbit corneas was demonstrated by viral growth curves and subpassage studies. Intracellular localization of adenoviral antigens was confirmed with immunofluorescent techniques. The characteristic cytopathic effects of adenoviral infection were observed with the use of various histochemical stains. Thus an in vitro corneal organ culture model was established for the study of the pathogenesis of corneal lesions in adenovirus EKC."}
{"id": "PMID:225292", "title": "Scanning immunoelectron microscopy markers.", "content": "Ultrastructural analysis of the cell surface and of membrane components such as antigens or receptor sites by scanning immunoelectron microscopy (immuno-SEM) has been the subject of extensive investigation during the past few years. We review the various immunologic and cytochemical techniques applied to SEM, which have employed latex particles, viruses, bacteriophages, protein A, ferritin, gold granules, hemocyanin and peroxidase as markers, and the advantages and disadvantages of these techniques. From current data, it is clear that immuno-SEM has much to offer in determining the distribution of specific cell surface sites and in positive and unambiguous identification of cell types in heterogeneous cell populations.", "contents": "Scanning immunoelectron microscopy markers. Ultrastructural analysis of the cell surface and of membrane components such as antigens or receptor sites by scanning immunoelectron microscopy (immuno-SEM) has been the subject of extensive investigation during the past few years. We review the various immunologic and cytochemical techniques applied to SEM, which have employed latex particles, viruses, bacteriophages, protein A, ferritin, gold granules, hemocyanin and peroxidase as markers, and the advantages and disadvantages of these techniques. From current data, it is clear that immuno-SEM has much to offer in determining the distribution of specific cell surface sites and in positive and unambiguous identification of cell types in heterogeneous cell populations."}
{"id": "PMID:225289", "title": "Tantalum oxide, silica and latex: effects on alveolar macrophage viability and lysozyme release.", "content": "Tantalum an experimental bronchographic material, may be retained in the lungs for a prolonged period following bronchography. The alveolar macrophage (AM) is a cell with potential for clearing tantalum particles from the airways. We studied the in vitro effects of tantalum oxide and two other particles, silca and latex, on rabbit AM viability and lysozyme release over 30 hours. Results indicate: 1) tantalum oxide, silica, and latex particles are ingested by rabbit AM in culture; 2) tantalum oxide and silica are both toxic to AM in vitro; and 3) tantalum oxide exerts its toxic effects less rapidly on AM than does silica. On the basis of these in vitro culture results we conclude that tantalum oxide may be toxic to alveolar macrophages in vivo. Delayed lung clearance of tantalum oxide particles may be due in part to their toxic effects on alveolar macrophages.", "contents": "Tantalum oxide, silica and latex: effects on alveolar macrophage viability and lysozyme release. Tantalum an experimental bronchographic material, may be retained in the lungs for a prolonged period following bronchography. The alveolar macrophage (AM) is a cell with potential for clearing tantalum particles from the airways. We studied the in vitro effects of tantalum oxide and two other particles, silca and latex, on rabbit AM viability and lysozyme release over 30 hours. Results indicate: 1) tantalum oxide, silica, and latex particles are ingested by rabbit AM in culture; 2) tantalum oxide and silica are both toxic to AM in vitro; and 3) tantalum oxide exerts its toxic effects less rapidly on AM than does silica. On the basis of these in vitro culture results we conclude that tantalum oxide may be toxic to alveolar macrophages in vivo. Delayed lung clearance of tantalum oxide particles may be due in part to their toxic effects on alveolar macrophages."}
{"id": "PMID:225293", "title": "[Papillomatous lactic-duct adenoma (pseudoPaget's disease of the mamilla)].", "content": "Papillomatosis and adenomatosis of the nipple ducts can be interpreted clinically as Paget's disease. Three patients with subareolar papillomatosis and adenomatosis are described. The name papillary adenoma of the nipple ducts (pseudo-Paget's disease has been proposed. The differentiation between the papillary adenoma of the nipple ducts and the genuine Paget's disease needs histological examination. The differential diagnosis is very important, because local excision of the diseased ducts represents the treatment of choice of the papillary adenoma of the nipple ducts. Radical mastectomy is always necessary in genuine Paget's disease since the adjacent lactiferous ducts are involved by the carcinoma.", "contents": "[Papillomatous lactic-duct adenoma (pseudoPaget's disease of the mamilla)]. Papillomatosis and adenomatosis of the nipple ducts can be interpreted clinically as Paget's disease. Three patients with subareolar papillomatosis and adenomatosis are described. The name papillary adenoma of the nipple ducts (pseudo-Paget's disease has been proposed. The differentiation between the papillary adenoma of the nipple ducts and the genuine Paget's disease needs histological examination. The differential diagnosis is very important, because local excision of the diseased ducts represents the treatment of choice of the papillary adenoma of the nipple ducts. Radical mastectomy is always necessary in genuine Paget's disease since the adjacent lactiferous ducts are involved by the carcinoma."}
{"id": "PMID:225290", "title": "Application of direct cannulation and injection lymphangiography to the study of the canine cardiac and pulmonary efferent mediastinal lymphatics.", "content": "Lymphangiograms of canine cardiac and pulmonary efferent mediastinal lymphatics were made by cannulation and injection of Ethiodol. Injections were made singly and serially. The mediastinal lymphatics and lymph nodes, which constitute the pathways of drainage of the heart and lungs, were delineated from the point of cannulation to the right and left inferior cervical region where the right lymphatic duct and thoracic duct are located. Lymphangiography reveals that the lymphatics which drain the heart and lungs may join to form common mediastinal lymphatic channels. Interconnections between mediastinal channels were demonstrated. The lymphatics terminated in the region of both the right lymphatic duct and thoracic duct in every subject. The so-called \"cardiac node of Drinker\" is usually a group of pretracheal nodes rather than a single node. The pretracheal nodes and those more cephalad receive drainage of lymph from both the heart and lungs. These studies suggest that lymph collected by cannulation of a \"cardiac\" lymphatic adjacent to the \"cardiac node\" will contain pulmonary as well as cardiac lymph. Thus the high flows reported by many investigators for \"cardiac\" lymph probably indicates that pulmonary lymph is mixed with cardiac lymph, and that the experimental data should be interpreted with this in mind.", "contents": "Application of direct cannulation and injection lymphangiography to the study of the canine cardiac and pulmonary efferent mediastinal lymphatics. Lymphangiograms of canine cardiac and pulmonary efferent mediastinal lymphatics were made by cannulation and injection of Ethiodol. Injections were made singly and serially. The mediastinal lymphatics and lymph nodes, which constitute the pathways of drainage of the heart and lungs, were delineated from the point of cannulation to the right and left inferior cervical region where the right lymphatic duct and thoracic duct are located. Lymphangiography reveals that the lymphatics which drain the heart and lungs may join to form common mediastinal lymphatic channels. Interconnections between mediastinal channels were demonstrated. The lymphatics terminated in the region of both the right lymphatic duct and thoracic duct in every subject. The so-called \"cardiac node of Drinker\" is usually a group of pretracheal nodes rather than a single node. The pretracheal nodes and those more cephalad receive drainage of lymph from both the heart and lungs. These studies suggest that lymph collected by cannulation of a \"cardiac\" lymphatic adjacent to the \"cardiac node\" will contain pulmonary as well as cardiac lymph. Thus the high flows reported by many investigators for \"cardiac\" lymph probably indicates that pulmonary lymph is mixed with cardiac lymph, and that the experimental data should be interpreted with this in mind."}
{"id": "PMID:225291", "title": "Isoproterenol in comparison to WR-2721 as a chemoradioprotector of the rat parotid gland.", "content": "A comparison was made of the radioprotective abilities of the chemoradioprotector WR-2721, an amino-thiol, and the beta-sympathomimetic secretogogue isoproterenol on the rat parotid gland. Using the dose-response curve of WR-2721 for gland weights as a basis for comparison, isoproterenol was found to offer significant and equal protection during both the acute (DMF, 2.5) and the chronic (DMF, 2.3) periods.", "contents": "Isoproterenol in comparison to WR-2721 as a chemoradioprotector of the rat parotid gland. A comparison was made of the radioprotective abilities of the chemoradioprotector WR-2721, an amino-thiol, and the beta-sympathomimetic secretogogue isoproterenol on the rat parotid gland. Using the dose-response curve of WR-2721 for gland weights as a basis for comparison, isoproterenol was found to offer significant and equal protection during both the acute (DMF, 2.5) and the chronic (DMF, 2.3) periods."}
{"id": "PMID:225295", "title": "Attachment of acetylcholinesterase to structures of the motor endplate.", "content": "The kinetics of AChE solubilization from intact motor endplates of mouse diaphragm, by collagenase, papain and hyaluronidase, was studied in parallel with the ultrastructural localization of AChE in treated neuromuscular junctions. Hyaluronidase did not solubilize more AChE from isolated motor endplate regions than Ringer's solution itself. Residual AChE activity could be demonstrated histochemically in motor endplates even after the plateau of solubilization by collagenase or papain was reached. Less than 35% of junctional AChE is left after collagenase, and less than 20% after papain treatment, as estimated by the percentage of AChE activity left in the isolated endplate region of the diaphragm after protease treatment. Cytochemically, both proteases had a similar effect on postsynaptic AChE. Residual AChE activity was distributed randomly, adhering to the sarcolemma of junctional clefts. Presynaptic AChE localized in the gap between axon terminal and Schwann cell appears to be resistant to collagenase but not to papain treatment. The mode of AChE attachment or the composition of the intercellular material in this gap may differ from that of the primary and secondary clefts.", "contents": "Attachment of acetylcholinesterase to structures of the motor endplate. The kinetics of AChE solubilization from intact motor endplates of mouse diaphragm, by collagenase, papain and hyaluronidase, was studied in parallel with the ultrastructural localization of AChE in treated neuromuscular junctions. Hyaluronidase did not solubilize more AChE from isolated motor endplate regions than Ringer's solution itself. Residual AChE activity could be demonstrated histochemically in motor endplates even after the plateau of solubilization by collagenase or papain was reached. Less than 35% of junctional AChE is left after collagenase, and less than 20% after papain treatment, as estimated by the percentage of AChE activity left in the isolated endplate region of the diaphragm after protease treatment. Cytochemically, both proteases had a similar effect on postsynaptic AChE. Residual AChE activity was distributed randomly, adhering to the sarcolemma of junctional clefts. Presynaptic AChE localized in the gap between axon terminal and Schwann cell appears to be resistant to collagenase but not to papain treatment. The mode of AChE attachment or the composition of the intercellular material in this gap may differ from that of the primary and secondary clefts."}
{"id": "PMID:225299", "title": "Haemophilus influenzae periplasmic protein which binds deoxyribonucleic acid: properties and possible participation in genetic transformation.", "content": "A protein which binds to either single-stranded or double-stranded deoxyribonucleic acid (DNA) but not to ribonucleic acid has been isolated by osmotic shock treatment of growing cells. This periplasmic protein differs from the principal intracellular binding protein in its greater thermolability and by the absence of salt-induced cooperativity in its interaction with single-stranded DNA. Certain mutant strains of Haemophilus influenzae defective in the DNA suptake steps of genetic transformation were found to be deficient in periplasmic DNA-binding protein, suggesting that this protein participates in the uptake of DNA in transformation.", "contents": "Haemophilus influenzae periplasmic protein which binds deoxyribonucleic acid: properties and possible participation in genetic transformation. A protein which binds to either single-stranded or double-stranded deoxyribonucleic acid (DNA) but not to ribonucleic acid has been isolated by osmotic shock treatment of growing cells. This periplasmic protein differs from the principal intracellular binding protein in its greater thermolability and by the absence of salt-induced cooperativity in its interaction with single-stranded DNA. Certain mutant strains of Haemophilus influenzae defective in the DNA suptake steps of genetic transformation were found to be deficient in periplasmic DNA-binding protein, suggesting that this protein participates in the uptake of DNA in transformation."}
{"id": "PMID:225298", "title": "Overview of selected basic research in autism.", "content": "Basic research in autism is reviewed. There is mounting indication, but as yet inconclusive evidence, of unique physiologic disturbances etiologically related to autism. Additionally there is indication that some of the physiologic disturbances found in autistic children are also present in children with other developmental disorders. Children called autistic probably represent a complex of clinically similar manifestations in a variety of different subgroups of children, each subgroup representing a basically different physiologic disturbance. However, the possibility remains that there is only one basic disturbance that in varying degrees affects many body systems and thus manifests in a variety of overlapping syndromes. Objective markers are needed so as to allow the demarcation of subgroups of autistic children for further study. Possible markers may be decreased duration of postrotatory nystagmus, auditory evoked response deviations, lymphocytic hyporesponsivity, increased blood platelet serotonin efflux, and/or the presence of urinary DMT or bufotenin.", "contents": "Overview of selected basic research in autism. Basic research in autism is reviewed. There is mounting indication, but as yet inconclusive evidence, of unique physiologic disturbances etiologically related to autism. Additionally there is indication that some of the physiologic disturbances found in autistic children are also present in children with other developmental disorders. Children called autistic probably represent a complex of clinically similar manifestations in a variety of different subgroups of children, each subgroup representing a basically different physiologic disturbance. However, the possibility remains that there is only one basic disturbance that in varying degrees affects many body systems and thus manifests in a variety of overlapping syndromes. Objective markers are needed so as to allow the demarcation of subgroups of autistic children for further study. Possible markers may be decreased duration of postrotatory nystagmus, auditory evoked response deviations, lymphocytic hyporesponsivity, increased blood platelet serotonin efflux, and/or the presence of urinary DMT or bufotenin."}
{"id": "PMID:225300", "title": "Methyl ester of hyaluronate is unable to stimulate exolipase formation by Serratia marcescens.", "content": "Hyaluronate stimulated the formation of exolipase by Serratia marcescens. This ability was abolished when all carboxyl groups of hyaluronate were methyl esterified. Additional studies suggested that the biological inactivity of esterified hyaluronate should be ascribed to the reduced conformational order of the molecules rather than to their electroneutrality.", "contents": "Methyl ester of hyaluronate is unable to stimulate exolipase formation by Serratia marcescens. Hyaluronate stimulated the formation of exolipase by Serratia marcescens. This ability was abolished when all carboxyl groups of hyaluronate were methyl esterified. Additional studies suggested that the biological inactivity of esterified hyaluronate should be ascribed to the reduced conformational order of the molecules rather than to their electroneutrality."}
{"id": "PMID:225301", "title": "Extrachromosomal psi+ determinant suppresses nonsense mutations in yeast.", "content": "The extrachromosomal psi+ determinant in the yeast Saccharomyces cerevisiae enhanced the expression of Mendelian UAA suppressors by 6- to 10-fold. The psi+ determinant by itself is a weak UAA suppressor that caused the production of approximately 1% of the normal level of iso-1-cytochrome c in a strain containing the UAA mutation cycl-72.", "contents": "Extrachromosomal psi+ determinant suppresses nonsense mutations in yeast. The extrachromosomal psi+ determinant in the yeast Saccharomyces cerevisiae enhanced the expression of Mendelian UAA suppressors by 6- to 10-fold. The psi+ determinant by itself is a weak UAA suppressor that caused the production of approximately 1% of the normal level of iso-1-cytochrome c in a strain containing the UAA mutation cycl-72."}
{"id": "PMID:225302", "title": "Nicotinamide adenine dinucleotide metabolism in Candida albicans.", "content": "The functional pathways of nicotinamide adenine dinucleotide (NAD) biosynthesis and their regulation were studied in the dimorphic fungus Candida albicans. The presence of a functional endogenous pathway of NAD biosynthesis from tryptophan was demonstrated. In addition, nicotinamide served as an efficient salvage precursor for NAD biosynthesis but nicotinate was not utilized. The pathway for nicotinamide utilization involved nicotinate and nicotinate nucleotides as intermediates, suggesting that the failure to utilize nicotinate involves a transport defect. The mechanisms that regulate NAD levels during exponential growth operated to maintain constant NAD levels when NAD biosynthesis occurred exclusively from endogenous or salvage pathways or from a combination of the two. The regulation also operated such that the salvage pathway was preferentially utilized.", "contents": "Nicotinamide adenine dinucleotide metabolism in Candida albicans. The functional pathways of nicotinamide adenine dinucleotide (NAD) biosynthesis and their regulation were studied in the dimorphic fungus Candida albicans. The presence of a functional endogenous pathway of NAD biosynthesis from tryptophan was demonstrated. In addition, nicotinamide served as an efficient salvage precursor for NAD biosynthesis but nicotinate was not utilized. The pathway for nicotinamide utilization involved nicotinate and nicotinate nucleotides as intermediates, suggesting that the failure to utilize nicotinate involves a transport defect. The mechanisms that regulate NAD levels during exponential growth operated to maintain constant NAD levels when NAD biosynthesis occurred exclusively from endogenous or salvage pathways or from a combination of the two. The regulation also operated such that the salvage pathway was preferentially utilized."}
{"id": "PMID:225303", "title": "Regulation of phosphoglycerate phosphomutase in developing forespores and dormant and germinated spores of Bacillus megaterium by the level of free manganous ions.", "content": "The large depot of phosphoglyceric acid (PGA) which is accumulated within spores of Bacillus megaterium is greater than 99% 3-phosphoglyceric acid (3-PGA). The 3-PGA depot is stable in forespores and dormant spores, but is utilized rapidly during spore germination. When spores were germinated in KBr plus NaF, the PGA depot was not utilized, but 13% of the 3-PGA was converted to 2-PGA. These data suggest phosphoglycerate phosphomutase as the enzyme which is regulated to allow 3-PGA accumulation during sporulation. Young isolated forespores, in which 3-PGA was normally stable, utilized their 3-PGA rapidly when incubated with Mn2+ plus the divalent cation ionophore X-537A; Mn2+ or ionophore alone or Mg2+ or Ca2+ plus ionophore was without effect. Young forespores contained significant amounts of Mn2+. However, forespore Mn2+ exchanged slowly with exogenous Mn2+ and was removed poorly by toluene treatment. This suggests that much of the forespore Mn2+ is tightly bound to some forespore component. Since phosphoglycerate phosphomutase from B. megaterium has an absolute and specific requirement for Mn2+, these data suggest that the activity of this enzyme in vivo may be regulated to a large degree by the level of free Mn2+. Indeed, the activity of this enzyme in forespore or dormant spore extracts was stimulated greater than 25-fold by Mn2+, whereas comparable extracts from cells or germinated spores were stimulated only two- to fourfold.", "contents": "Regulation of phosphoglycerate phosphomutase in developing forespores and dormant and germinated spores of Bacillus megaterium by the level of free manganous ions. The large depot of phosphoglyceric acid (PGA) which is accumulated within spores of Bacillus megaterium is greater than 99% 3-phosphoglyceric acid (3-PGA). The 3-PGA depot is stable in forespores and dormant spores, but is utilized rapidly during spore germination. When spores were germinated in KBr plus NaF, the PGA depot was not utilized, but 13% of the 3-PGA was converted to 2-PGA. These data suggest phosphoglycerate phosphomutase as the enzyme which is regulated to allow 3-PGA accumulation during sporulation. Young isolated forespores, in which 3-PGA was normally stable, utilized their 3-PGA rapidly when incubated with Mn2+ plus the divalent cation ionophore X-537A; Mn2+ or ionophore alone or Mg2+ or Ca2+ plus ionophore was without effect. Young forespores contained significant amounts of Mn2+. However, forespore Mn2+ exchanged slowly with exogenous Mn2+ and was removed poorly by toluene treatment. This suggests that much of the forespore Mn2+ is tightly bound to some forespore component. Since phosphoglycerate phosphomutase from B. megaterium has an absolute and specific requirement for Mn2+, these data suggest that the activity of this enzyme in vivo may be regulated to a large degree by the level of free Mn2+. Indeed, the activity of this enzyme in forespore or dormant spore extracts was stimulated greater than 25-fold by Mn2+, whereas comparable extracts from cells or germinated spores were stimulated only two- to fourfold."}
{"id": "PMID:225304", "title": "Electric and flow birefringence properties of myosin in aqueous urea and sodium pyrophosphate.", "content": "The electric dipole moment of rabbit skeletal myosin was estimated from the electric and flow birefringence properties. Myosin formed small polydisperse aggregates (0.2-1.1 microM in length) with an apparent electric dipole moment of 5,000-20,000 Debye in aqueous urea or sodium pyrophosphate at low ionic strength. Permanent dipole moment contributed substantially to the apparent dipole moment. An anti-parallel association of myosin was suggested from the dependence of the apparent dipole moment on myosin concentration. Some interactions between myosin and C-protein were detected in 1 M urea by flow birefringence and analytical ultracentrifugation studies. The apparent dipole moment of myosin aggregates was less dependent on myosin concentration in the presence of C-protein.", "contents": "Electric and flow birefringence properties of myosin in aqueous urea and sodium pyrophosphate. The electric dipole moment of rabbit skeletal myosin was estimated from the electric and flow birefringence properties. Myosin formed small polydisperse aggregates (0.2-1.1 microM in length) with an apparent electric dipole moment of 5,000-20,000 Debye in aqueous urea or sodium pyrophosphate at low ionic strength. Permanent dipole moment contributed substantially to the apparent dipole moment. An anti-parallel association of myosin was suggested from the dependence of the apparent dipole moment on myosin concentration. Some interactions between myosin and C-protein were detected in 1 M urea by flow birefringence and analytical ultracentrifugation studies. The apparent dipole moment of myosin aggregates was less dependent on myosin concentration in the presence of C-protein."}
{"id": "PMID:225305", "title": "The use of soybean trypsin inhibitors as phosphorylatable substrates for a rat liver protein kinase.", "content": "Phosphorylation by a cAMP-independent rat liver protein kinase of protein substrates containing the structural feature required by mammary gland casein kinase (-Ser-X-Glu/Asp) has been demonstrated. In particular, the Bowman-Birk Soybean trypsin inhibitor, which is characterized, like other legume protease inhibitors, by clusters of acidic residues near the C-terminal side of seryl residue(s), proved to be a good model substrate for the protein kinase. Its phosphorylation, involving the Ser 65 residue, is apparently hindered by the binding of trypsin, while it is stimulated by unfolding induced by reduction and subsequent carboxy-methylation.", "contents": "The use of soybean trypsin inhibitors as phosphorylatable substrates for a rat liver protein kinase. Phosphorylation by a cAMP-independent rat liver protein kinase of protein substrates containing the structural feature required by mammary gland casein kinase (-Ser-X-Glu/Asp) has been demonstrated. In particular, the Bowman-Birk Soybean trypsin inhibitor, which is characterized, like other legume protease inhibitors, by clusters of acidic residues near the C-terminal side of seryl residue(s), proved to be a good model substrate for the protein kinase. Its phosphorylation, involving the Ser 65 residue, is apparently hindered by the binding of trypsin, while it is stimulated by unfolding induced by reduction and subsequent carboxy-methylation."}
{"id": "PMID:225306", "title": "Studies on regulatory functions of malic enzymes. IV. Effects of sulfhydryl group modification on the catalytic function of NAD-linked malic enzyme from Escherichia coli.", "content": "Reactions catalyzed by NAD-linked malic enzyme from Escherichia coli were investigated. In addition to L-malate oxidative decarboxylase activity (Activity 1) and oxaloacetate decarboxylase activity (Activity 2), the enzyme exhibited oxaloacetate reductase activity (Activity 3) and pyruvate reductase activity (Activity 4). Optimum pH's for Activities 3 and 4 were 4.0 and 5.0, and their specific activities were 1.7 and 0.07, respectively. Upon reaction with N-ethylmaleimide (NEM), Activity 1 decreased following pseudo-first order kinetics. Activity 2 decreased in parallel with Activity 1, while Activities 3 and 4 were about ten-fold enhanced by NEM modification. Modification of one or two sulfhydryl groups per enzyme subunit caused an alteration of the activities. Tartronate, a substrate analog, NAD+, and Mn2+ protected the enzyme against the modification. The Km values for the substrates and coenzymes were not significantly affected by NEM modification. Similarly, other sulfhydryl reagents such as p-hydroxymercuribenzoate (PMB), 5,5'-dithiobis(2-nitrobenzoate) (DTNB), and iodoacetate inhibited the decarboxylase activities and activated the reductase activities to various extents. Modification of the enzyme with PMB or DTNB was reversed by the addition of a sulfhydryl compound such as dithiothreitol or 2-mercaptoethanol. Based on the above results, the mechanism of the alteration of enzyme activities by sulfhydryl group modification is discussed.", "contents": "Studies on regulatory functions of malic enzymes. IV. Effects of sulfhydryl group modification on the catalytic function of NAD-linked malic enzyme from Escherichia coli. Reactions catalyzed by NAD-linked malic enzyme from Escherichia coli were investigated. In addition to L-malate oxidative decarboxylase activity (Activity 1) and oxaloacetate decarboxylase activity (Activity 2), the enzyme exhibited oxaloacetate reductase activity (Activity 3) and pyruvate reductase activity (Activity 4). Optimum pH's for Activities 3 and 4 were 4.0 and 5.0, and their specific activities were 1.7 and 0.07, respectively. Upon reaction with N-ethylmaleimide (NEM), Activity 1 decreased following pseudo-first order kinetics. Activity 2 decreased in parallel with Activity 1, while Activities 3 and 4 were about ten-fold enhanced by NEM modification. Modification of one or two sulfhydryl groups per enzyme subunit caused an alteration of the activities. Tartronate, a substrate analog, NAD+, and Mn2+ protected the enzyme against the modification. The Km values for the substrates and coenzymes were not significantly affected by NEM modification. Similarly, other sulfhydryl reagents such as p-hydroxymercuribenzoate (PMB), 5,5'-dithiobis(2-nitrobenzoate) (DTNB), and iodoacetate inhibited the decarboxylase activities and activated the reductase activities to various extents. Modification of the enzyme with PMB or DTNB was reversed by the addition of a sulfhydryl compound such as dithiothreitol or 2-mercaptoethanol. Based on the above results, the mechanism of the alteration of enzyme activities by sulfhydryl group modification is discussed."}
{"id": "PMID:225307", "title": "Construction of a multilayer planar membrane applicable to ion-transport measurement.", "content": "Multilayer planar membranes applicable to ion-transport measurements were constructed from egg yolk lecithin, egg yolk lecithin-cholesterol mixture, and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine between two tightly stretched cellulose sheets. While most of the phospholipids in the membranes were found by a spin label technique to be uniformly oriented with their long hydrocarbon chains perpendicular to the surfaces of the cellulose sheets, a small fraction of phospholipids were isotropically oriented in multilayer membranes. The amount of phospholipids with isotropic orientations decreased with increasing content of cholesterol in membranes and became zero in membranes of egg yolk lecithin-cholesterol mixture (molar ratio of 1: 0.67). The degree of orientation, S, of uniformly oriented phospholipids in membranes was also increased by adding cholesterol to the membranes. The orientation of phospholipids in membranes was rather stable in distilled water and in aqueous calcium chloride (1, 10, 100 mM), while a marked disordering of oriented phospholipids was induced in a aqueous solutions containing thymol, isopropanol, or butanol beyond certain specific concentrations. The membranes can be used for measurements of calcium permeation. An appreciable barrier function to calcium permeation was detected with these multilayer planar membranes as compared with control experiments using only cellulose sheets as membranes. A preliminary investigation suggested that changes in the orientational structure of phospholipids in the multilayer planar membranes are correlated with permeability properties of the membranes.", "contents": "Construction of a multilayer planar membrane applicable to ion-transport measurement. Multilayer planar membranes applicable to ion-transport measurements were constructed from egg yolk lecithin, egg yolk lecithin-cholesterol mixture, and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine between two tightly stretched cellulose sheets. While most of the phospholipids in the membranes were found by a spin label technique to be uniformly oriented with their long hydrocarbon chains perpendicular to the surfaces of the cellulose sheets, a small fraction of phospholipids were isotropically oriented in multilayer membranes. The amount of phospholipids with isotropic orientations decreased with increasing content of cholesterol in membranes and became zero in membranes of egg yolk lecithin-cholesterol mixture (molar ratio of 1: 0.67). The degree of orientation, S, of uniformly oriented phospholipids in membranes was also increased by adding cholesterol to the membranes. The orientation of phospholipids in membranes was rather stable in distilled water and in aqueous calcium chloride (1, 10, 100 mM), while a marked disordering of oriented phospholipids was induced in a aqueous solutions containing thymol, isopropanol, or butanol beyond certain specific concentrations. The membranes can be used for measurements of calcium permeation. An appreciable barrier function to calcium permeation was detected with these multilayer planar membranes as compared with control experiments using only cellulose sheets as membranes. A preliminary investigation suggested that changes in the orientational structure of phospholipids in the multilayer planar membranes are correlated with permeability properties of the membranes."}
{"id": "PMID:225308", "title": "Evidence for bactericidal activity of polymorphonuclear leukocytes without phagocytosis.", "content": "The relationship between phagocytosis and bactericidal action of polymorphonuclear leukocytes was examined by comparing the functions of cytochalasin D-treated leukocytes with those of the control. Measurement of phagocytotic and bacterial DNA-degrading activities using Escherichia coli prelabeled with [3H]thymidine revealed that phagocytosis and bacterial DNA degradation were inhibited by treatment with cytochalasin D to about 50 and 10% of the control, respectively. Nevertheless, the bactericidal activity of the cytochalasin D-treated leukocytes was almost the same as that of the control leukocytes; almost all the bacteria were phagocytized by the latter leukocytes. Under the same experimental conditions, the production and release of superoxide anions and hydrogen peroxide, which are both known to be involved in the bactericidal action of the leukocytes, were markedly increased by cytochalasin D. Release of several lysosomal hydrolases was also increased markedly by cytochalasin D treatment, except for myeloperoxidase. However, lactate dehydrogenase, a typical cytosolic marker, was not released by the same treatment. Thus, it is unlikely that the increase in the release of the above-mentioned bactericidal factors was due to decomposition of the leukocytes. These results indicate that the site of bactericidal action of cytochalasin D-treated leukocytes is not necessarily intracellular but may be around the external surface of the cells.", "contents": "Evidence for bactericidal activity of polymorphonuclear leukocytes without phagocytosis. The relationship between phagocytosis and bactericidal action of polymorphonuclear leukocytes was examined by comparing the functions of cytochalasin D-treated leukocytes with those of the control. Measurement of phagocytotic and bacterial DNA-degrading activities using Escherichia coli prelabeled with [3H]thymidine revealed that phagocytosis and bacterial DNA degradation were inhibited by treatment with cytochalasin D to about 50 and 10% of the control, respectively. Nevertheless, the bactericidal activity of the cytochalasin D-treated leukocytes was almost the same as that of the control leukocytes; almost all the bacteria were phagocytized by the latter leukocytes. Under the same experimental conditions, the production and release of superoxide anions and hydrogen peroxide, which are both known to be involved in the bactericidal action of the leukocytes, were markedly increased by cytochalasin D. Release of several lysosomal hydrolases was also increased markedly by cytochalasin D treatment, except for myeloperoxidase. However, lactate dehydrogenase, a typical cytosolic marker, was not released by the same treatment. Thus, it is unlikely that the increase in the release of the above-mentioned bactericidal factors was due to decomposition of the leukocytes. These results indicate that the site of bactericidal action of cytochalasin D-treated leukocytes is not necessarily intracellular but may be around the external surface of the cells."}
{"id": "PMID:225310", "title": "A role of membranes in the activation of a new multifunctional protein kinase system.", "content": "A new multifunctional protein kinase, which normally exists as an inactive form in the soluble fraction in mammalian tissues, attaches to membranes to exhibit full enzymatic activity. A low concentration of Ca2+ is absolutely necessary for this activation. This process is reversible. cAMP shows no effect. The active factors in membranes are phosphatidylinositol, phosphatidylserine, phosphatidic acid, diphosphatidylglycerol, and phosphatidylethanolamine in that order. Phosphatidylcholine and sphingomyelin are far less effective. Cytoplasmic as well as other membrane fractions from various tissues are active in supporting the enzymatic activity. A possible role of this Ca2+ and phospholipid-activated protein kinase system in transmembrane control is proposed.", "contents": "A role of membranes in the activation of a new multifunctional protein kinase system. A new multifunctional protein kinase, which normally exists as an inactive form in the soluble fraction in mammalian tissues, attaches to membranes to exhibit full enzymatic activity. A low concentration of Ca2+ is absolutely necessary for this activation. This process is reversible. cAMP shows no effect. The active factors in membranes are phosphatidylinositol, phosphatidylserine, phosphatidic acid, diphosphatidylglycerol, and phosphatidylethanolamine in that order. Phosphatidylcholine and sphingomyelin are far less effective. Cytoplasmic as well as other membrane fractions from various tissues are active in supporting the enzymatic activity. A possible role of this Ca2+ and phospholipid-activated protein kinase system in transmembrane control is proposed."}
{"id": "PMID:225311", "title": "Evidence for the existence of a novel enzyme system. myo-Inositol-1-phosphate dehydrogenase in Phaseolus aureus.", "content": "A novel enzyme system, myo-inositol-1-phosphate dehydrogenase, has been isolated from germinating mung bean seeds. The dehydrogenation and cleavage of myo-inositol 1-phosphate by this enzyme leads to the synthesis of a pentose phosphate which appears to be ribulose 5-phosphate. The pH optimum of the enzyme is 8.6; NAD+ is required as coenzyme and no other nucleotides can replace NAD+. Mono- or divalent cations are not essential for the enzyme activity. Stoichiometry of the  reaction suggests that 2 mol of NAD+ are reduced per mol of ribulose-5-P generated.", "contents": "Evidence for the existence of a novel enzyme system. myo-Inositol-1-phosphate dehydrogenase in Phaseolus aureus. A novel enzyme system, myo-inositol-1-phosphate dehydrogenase, has been isolated from germinating mung bean seeds. The dehydrogenation and cleavage of myo-inositol 1-phosphate by this enzyme leads to the synthesis of a pentose phosphate which appears to be ribulose 5-phosphate. The pH optimum of the enzyme is 8.6; NAD+ is required as coenzyme and no other nucleotides can replace NAD+. Mono- or divalent cations are not essential for the enzyme activity. Stoichiometry of the  reaction suggests that 2 mol of NAD+ are reduced per mol of ribulose-5-P generated."}
{"id": "PMID:225312", "title": "Isolation and characterization of cultured mouse T-lymphoma cells deficient in uridine-cytidine kinase.", "content": "Two clones were isolated from mutagenized mouse T-lymphoma cells (S49) which are over 90% deficient in uridine-cytidine kinase. The first clone, AU-200-1, was isolated in two steps by virtue of its resistance to 6-azauridine; whereas the second clone, FU3-70G, was isolated in three steps after exposure to three increasing concentrations of 5-fluorouracil. Extracts of both the AU-200-1 and the FU3-70G cell lines lacked over 90% of the capacity of those from wild type cells to phosphorylate either uridine or cytidine. Furthermore, the uptake of radioactive uridine and cytidine from the medium by intact AU-200-1 and FU3-70G cells was less than 5% of that found for intact wild type cells. By growth rate experiments, these uridine-cytidine kinase-deficient cell lines have altered sensitivities to the toxic pyrimidine analogs, 6-azauridine, 5-fluorouracil, and 5-fluorouridine and thus have been useful in elucidating the biochemical determinants involved in the metabolism of these compounds.", "contents": "Isolation and characterization of cultured mouse T-lymphoma cells deficient in uridine-cytidine kinase. Two clones were isolated from mutagenized mouse T-lymphoma cells (S49) which are over 90% deficient in uridine-cytidine kinase. The first clone, AU-200-1, was isolated in two steps by virtue of its resistance to 6-azauridine; whereas the second clone, FU3-70G, was isolated in three steps after exposure to three increasing concentrations of 5-fluorouracil. Extracts of both the AU-200-1 and the FU3-70G cell lines lacked over 90% of the capacity of those from wild type cells to phosphorylate either uridine or cytidine. Furthermore, the uptake of radioactive uridine and cytidine from the medium by intact AU-200-1 and FU3-70G cells was less than 5% of that found for intact wild type cells. By growth rate experiments, these uridine-cytidine kinase-deficient cell lines have altered sensitivities to the toxic pyrimidine analogs, 6-azauridine, 5-fluorouracil, and 5-fluorouridine and thus have been useful in elucidating the biochemical determinants involved in the metabolism of these compounds."}
{"id": "PMID:225313", "title": "Active site phosphohistidine peptides from red cell bisphosphoglycerate synthase and yeast phosphoglycerate mutase.", "content": "Bisphosphoglycerate synthase (glycerate-1,3-P2 yields glycerate-2,3-P2) and phosphoglycerate mutase (glycerate-3-P formed from glycerate-2-P) are both phosphorylated by substrates at a histidine residue forming covalent intermediates which have been shown to function in the phosphoryl transfer reactions catalyzed by these enzymes (Rose, Z. B., and Dube, S. (1976) J. Biol. Chem. 251, 4817--4822). We have phosphorylated bisphosphoglycerate synthase from horse red blood cells with [U-32P]glycerate-2,3-P2, digested with trypsin, and purified the phosphopeptide. The amino acid sequence of the phosphohistidine peptide has been determined to be: His-Gly-Gln-Gly-Ala-Trp-Asn-Lys. In like manner, a phosphohistidyl peptide has now been purified from yeast phosphoglycerate mutase, for which the amino acid sequence is known (Winn, S. I., Watson, H. C., Fothergill, L. A., and Harkins, R. N. (1977) Biochem. Soc. Trans. 5, 657-659). The amino acid composition of the phosphopeptide indicates that histidine-8 was phosphorylated. The sequence of this peptide is closely homologous with the active site peptide from bisphosphoglycerate synthase. In yeast phosphoglycerate mutase, the denatured phosphoenzyme hydrolyzes with a single rate constant of 2.02 X 10(-4) s-1 at pH 3, 45 degrees C. The relevance of these observations to the enzymatic mechanism is discussed.", "contents": "Active site phosphohistidine peptides from red cell bisphosphoglycerate synthase and yeast phosphoglycerate mutase. Bisphosphoglycerate synthase (glycerate-1,3-P2 yields glycerate-2,3-P2) and phosphoglycerate mutase (glycerate-3-P formed from glycerate-2-P) are both phosphorylated by substrates at a histidine residue forming covalent intermediates which have been shown to function in the phosphoryl transfer reactions catalyzed by these enzymes (Rose, Z. B., and Dube, S. (1976) J. Biol. Chem. 251, 4817--4822). We have phosphorylated bisphosphoglycerate synthase from horse red blood cells with [U-32P]glycerate-2,3-P2, digested with trypsin, and purified the phosphopeptide. The amino acid sequence of the phosphohistidine peptide has been determined to be: His-Gly-Gln-Gly-Ala-Trp-Asn-Lys. In like manner, a phosphohistidyl peptide has now been purified from yeast phosphoglycerate mutase, for which the amino acid sequence is known (Winn, S. I., Watson, H. C., Fothergill, L. A., and Harkins, R. N. (1977) Biochem. Soc. Trans. 5, 657-659). The amino acid composition of the phosphopeptide indicates that histidine-8 was phosphorylated. The sequence of this peptide is closely homologous with the active site peptide from bisphosphoglycerate synthase. In yeast phosphoglycerate mutase, the denatured phosphoenzyme hydrolyzes with a single rate constant of 2.02 X 10(-4) s-1 at pH 3, 45 degrees C. The relevance of these observations to the enzymatic mechanism is discussed."}
{"id": "PMID:225314", "title": "Characteristics of chylomicron binding and lipid uptake by endothelial cells in culture.", "content": "Bovine vascular endothelial cells bind chylomicrons via a high affinity membrane receptor site. Subsequent to binding, the chylomicron apoprotein was neither internalized nor degraded by either sparse or confluent (contact-inhibited) cells. However, the adsorption of chylomicrons was associated with interiorization of chylomicron cholesteryl ester and triglyceride and the hydrolysis of these lipids to free cholesterol and unesterified fatty acids by a lysosome-dependent pathway. This pathway was active in both subconfluent and contact-inhibited cells. The chylomicron free cholesterol so produced inhibited endogeneous cholesterol synthesis measured in terms of the incorporation of [1-14C]-acetate into sterol. An excess of high density lipoprotein was 2- to 3-fold more effective in reducing both binding of chylomicrons and interiorization of chylomicron lipid than was low density lipoprotein. Chylomicron binding was not \"down-regulated\" by preincubation of the cells with low density lipoprotein or chylomicrons. The results are discussed in the context of cholesterol sources for contact-inhibited endothelial cells which do not interiorize low density lipoprotein cholesterol.", "contents": "Characteristics of chylomicron binding and lipid uptake by endothelial cells in culture. Bovine vascular endothelial cells bind chylomicrons via a high affinity membrane receptor site. Subsequent to binding, the chylomicron apoprotein was neither internalized nor degraded by either sparse or confluent (contact-inhibited) cells. However, the adsorption of chylomicrons was associated with interiorization of chylomicron cholesteryl ester and triglyceride and the hydrolysis of these lipids to free cholesterol and unesterified fatty acids by a lysosome-dependent pathway. This pathway was active in both subconfluent and contact-inhibited cells. The chylomicron free cholesterol so produced inhibited endogeneous cholesterol synthesis measured in terms of the incorporation of [1-14C]-acetate into sterol. An excess of high density lipoprotein was 2- to 3-fold more effective in reducing both binding of chylomicrons and interiorization of chylomicron lipid than was low density lipoprotein. Chylomicron binding was not \"down-regulated\" by preincubation of the cells with low density lipoprotein or chylomicrons. The results are discussed in the context of cholesterol sources for contact-inhibited endothelial cells which do not interiorize low density lipoprotein cholesterol."}
{"id": "PMID:225317", "title": "The fat cell adenylate cyclase system. Characterization and manipulation of its bimodal regulation by GTP.", "content": "GTP evoked both an activatory and an inhibitory response from adipocyte adenylate cyclase. This paper describes the persistence of the bimodal response under a variety of assay conditions. Additionally, manipulations are described which eliminate one or other of these actions. Treatment of adipocyte plasma membranes with cholera toxin A1 peptide and NAD+ abolishes the inhibitory phase of GTP action while preserving the activating phase. Treatment of the membranes with p-hydroxymercuriphenylsulfonic acid eliminates the activatory phase while maintaining the inhibitory processes mediated by GTP in adipocytes normally coexist and operate through different pathways since either phase can be abolished leaving the other intact. Adenosine and its purine-modified analogs inhibit fat cell adenylate cyclase in the GTP inhibitory phase (Londos, C., Cooper, D. M. F., Schlegel, W., and Rodbell, M. (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 5362-5366). When this effect of GTP is abolished by either cholera toxin or Gpp(NH)p pretreatment, the inhibitory action of adenosine analogs is also lost. These data suggest a central role for GTP in mediating both activation and inhibition of adenylate cyclase by agents which act through cell surface receptors.", "contents": "The fat cell adenylate cyclase system. Characterization and manipulation of its bimodal regulation by GTP. GTP evoked both an activatory and an inhibitory response from adipocyte adenylate cyclase. This paper describes the persistence of the bimodal response under a variety of assay conditions. Additionally, manipulations are described which eliminate one or other of these actions. Treatment of adipocyte plasma membranes with cholera toxin A1 peptide and NAD+ abolishes the inhibitory phase of GTP action while preserving the activating phase. Treatment of the membranes with p-hydroxymercuriphenylsulfonic acid eliminates the activatory phase while maintaining the inhibitory processes mediated by GTP in adipocytes normally coexist and operate through different pathways since either phase can be abolished leaving the other intact. Adenosine and its purine-modified analogs inhibit fat cell adenylate cyclase in the GTP inhibitory phase (Londos, C., Cooper, D. M. F., Schlegel, W., and Rodbell, M. (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 5362-5366). When this effect of GTP is abolished by either cholera toxin or Gpp(NH)p pretreatment, the inhibitory action of adenosine analogs is also lost. These data suggest a central role for GTP in mediating both activation and inhibition of adenylate cyclase by agents which act through cell surface receptors."}
{"id": "PMID:225319", "title": "Dansylated thyrotropin as a probe of hormone-receptor interactions.", "content": "A strongly fluorescent 5-dimethylamino-1-naphthalene sulfonate (dansyl) derivative of bovine thyrotropin has been prepared. The dye-conjugated hormone is bioactive and shares, essentially unchanged, the membrane binding and adenylate cyclase stimulatory activities of the native hormone. Binding of 125I-labeled dansyl-thyrotropin to thyroid plasma membranes is sensitive to inhibition by gangliosides and, as is the case for the binding of 125I-thyrotropin, galactosyl-N-acetylgalactosaminyl[N-acetylneuraminyl-N-acetylneuraminyl]-galactosylglucosylceramide (GDIb) is the most potent binding inhibitor. Gangliosides interact with dansyl-thyrotropin, causing a large increase of the quantum yield and a 5- to 10-nm blue shift of the emission maximum of the hormone-bound naphthalene chromophore; gangliosides cause no change in the fluorescent properties of the free dye. The fluorescence enhancement caused by gangliosides can be specifically reversed by unlabeled thyrotropin. The effect of gangliosides on dansyl-thyrotropin fluorescence is strongly salt-dependent; salts cannot, however, reverse the formation of the dansyl-thyrotropin.ganglioside complex once it has formed. The salt data suggest that the association of the ganglioside with dansyl-thyrotropin is dominated by electrostatic interactions, but that salt-independent, short range interactions, most likely hydrophobic, dominate the dissociation of the dansyl-thyrotropin-ganglioside adduct. Sucrose gradient centrifugation, ultracentrifugation, and fluorescence polarization data indicate that the gangliosides are micellar in nature under the conditions of these experiments. Acid titration of dansyl-thyrotropin causes a marked quenching of dansyl fluorescence which in part reflects dissociation of the hormone into its constituent alpha and beta subunits. In the presence of GDIb, but not N-acetylneuraminylgalactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosylceramide (GDIa), pH-dependent quenching and subunit dissociation are essentially eliminated. Circular dichroism results and fluorescence polarization studies support the interpretation that the ganglioside interaction causes a conformational change in the thyrotropin molecule. The acid titration data together with differences in the ability of gangliosides to influence the tyrosine fluorescence of the thyrotropin molecule indicate that different gangliosides induce different conformational perturbations in the thyrotropin molecule.", "contents": "Dansylated thyrotropin as a probe of hormone-receptor interactions. A strongly fluorescent 5-dimethylamino-1-naphthalene sulfonate (dansyl) derivative of bovine thyrotropin has been prepared. The dye-conjugated hormone is bioactive and shares, essentially unchanged, the membrane binding and adenylate cyclase stimulatory activities of the native hormone. Binding of 125I-labeled dansyl-thyrotropin to thyroid plasma membranes is sensitive to inhibition by gangliosides and, as is the case for the binding of 125I-thyrotropin, galactosyl-N-acetylgalactosaminyl[N-acetylneuraminyl-N-acetylneuraminyl]-galactosylglucosylceramide (GDIb) is the most potent binding inhibitor. Gangliosides interact with dansyl-thyrotropin, causing a large increase of the quantum yield and a 5- to 10-nm blue shift of the emission maximum of the hormone-bound naphthalene chromophore; gangliosides cause no change in the fluorescent properties of the free dye. The fluorescence enhancement caused by gangliosides can be specifically reversed by unlabeled thyrotropin. The effect of gangliosides on dansyl-thyrotropin fluorescence is strongly salt-dependent; salts cannot, however, reverse the formation of the dansyl-thyrotropin.ganglioside complex once it has formed. The salt data suggest that the association of the ganglioside with dansyl-thyrotropin is dominated by electrostatic interactions, but that salt-independent, short range interactions, most likely hydrophobic, dominate the dissociation of the dansyl-thyrotropin-ganglioside adduct. Sucrose gradient centrifugation, ultracentrifugation, and fluorescence polarization data indicate that the gangliosides are micellar in nature under the conditions of these experiments. Acid titration of dansyl-thyrotropin causes a marked quenching of dansyl fluorescence which in part reflects dissociation of the hormone into its constituent alpha and beta subunits. In the presence of GDIb, but not N-acetylneuraminylgalactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosylceramide (GDIa), pH-dependent quenching and subunit dissociation are essentially eliminated. Circular dichroism results and fluorescence polarization studies support the interpretation that the ganglioside interaction causes a conformational change in the thyrotropin molecule. The acid titration data together with differences in the ability of gangliosides to influence the tyrosine fluorescence of the thyrotropin molecule indicate that different gangliosides induce different conformational perturbations in the thyrotropin molecule."}
{"id": "PMID:225320", "title": "Role of phospholipids in the structure and function of the thyrotropin receptor.", "content": "Phosphatidylinositol, phosphatidylserine, and phosphatidylethanolamine interact with 125I-thyrotropin and inhibit its binding to thyroid plasma membranes; phosphatidylcholine is not similarly effective. The interaction has been monitored by column chromatography on Sephadex G-100 which shows, for example, that 125I-labeled thyrotropin forms an adduct with phosphatidylinositol but not with phosphatidylcholine. Formation of the 125I-labeled thyrotropin-phosphatidylinositol adduct is dependent on the phosphatidylinositol concentration but can be reversed by both unlabeled thyrotropin and excess membranes. The efficacy of the phospholipid interaction and the phospholipid inhibition of thyrotropin binding to thyroid membranes is paralleled by changes in fluorescence and fluorescence polarization imposed on the 5-dimethylamino-1-naphthalene sulfonate (dansyl) derivative of thyrotropin. These changes are reversed by unlabeled thyrotropin but not by prolactin, placental lactogen, or growth hormone; similar changes are not observed when phospholipids are incubated with dansylated growth hormone, prolactin, and placental lactogen. Monovalent potassium, sodium, and lithium salts neither prevent nor reverse the formation of the phospholipid-dansyl-thyrotropin adduct; these results contrast with the effects of the same salts on the formation of ganglioside adducts with dansyl-thyrotropin. Despite their ability to interact witw 125I-thyrotropin in solution, neither phosphatidylinositol, phosphatidylserine, nor phosphatidylethanolamine, when incorporated in a liposome, binds the 125I-labeled ligand. These same phospholipids have no effect on ganglioside binding of 125I-labeled thyrotropin when gangliosides are incorporated in a liposome. These phospholipids do, however, modulate the expression of the glycoprotein component of the thyrotropin receptor when it is imbedded in a liposome. The phosphatidylinositol in this case serves as a negative modulator, both by decreasing the incorporation of the glycoprotein component of the receptor into the liposome and by inhibiting the binding activity of the glycoprotein component which is incorporated. Speculation is offered as to a possible role of the phospholipids in the message transmission process which would be consistent with current studies demonstrating a direct interaction of acidic phospholipids with thyrotropin. The effect of phospholipids on liposomes containing the glycoprotein component of the thyrotropin receptor raises the possibility that phospholipids and, in particular, phosphatidylinositol, may also play a role in regulating the insertion and expression of this receptor component in thyroid plasma membranes.", "contents": "Role of phospholipids in the structure and function of the thyrotropin receptor. Phosphatidylinositol, phosphatidylserine, and phosphatidylethanolamine interact with 125I-thyrotropin and inhibit its binding to thyroid plasma membranes; phosphatidylcholine is not similarly effective. The interaction has been monitored by column chromatography on Sephadex G-100 which shows, for example, that 125I-labeled thyrotropin forms an adduct with phosphatidylinositol but not with phosphatidylcholine. Formation of the 125I-labeled thyrotropin-phosphatidylinositol adduct is dependent on the phosphatidylinositol concentration but can be reversed by both unlabeled thyrotropin and excess membranes. The efficacy of the phospholipid interaction and the phospholipid inhibition of thyrotropin binding to thyroid membranes is paralleled by changes in fluorescence and fluorescence polarization imposed on the 5-dimethylamino-1-naphthalene sulfonate (dansyl) derivative of thyrotropin. These changes are reversed by unlabeled thyrotropin but not by prolactin, placental lactogen, or growth hormone; similar changes are not observed when phospholipids are incubated with dansylated growth hormone, prolactin, and placental lactogen. Monovalent potassium, sodium, and lithium salts neither prevent nor reverse the formation of the phospholipid-dansyl-thyrotropin adduct; these results contrast with the effects of the same salts on the formation of ganglioside adducts with dansyl-thyrotropin. Despite their ability to interact witw 125I-thyrotropin in solution, neither phosphatidylinositol, phosphatidylserine, nor phosphatidylethanolamine, when incorporated in a liposome, binds the 125I-labeled ligand. These same phospholipids have no effect on ganglioside binding of 125I-labeled thyrotropin when gangliosides are incorporated in a liposome. These phospholipids do, however, modulate the expression of the glycoprotein component of the thyrotropin receptor when it is imbedded in a liposome. The phosphatidylinositol in this case serves as a negative modulator, both by decreasing the incorporation of the glycoprotein component of the receptor into the liposome and by inhibiting the binding activity of the glycoprotein component which is incorporated. Speculation is offered as to a possible role of the phospholipids in the message transmission process which would be consistent with current studies demonstrating a direct interaction of acidic phospholipids with thyrotropin. The effect of phospholipids on liposomes containing the glycoprotein component of the thyrotropin receptor raises the possibility that phospholipids and, in particular, phosphatidylinositol, may also play a role in regulating the insertion and expression of this receptor component in thyroid plasma membranes."}
{"id": "PMID:225321", "title": "NADH binding to porcine mitochondrial malate dehydrogenase.", "content": "The binding of NADH to porcine mitochondrial malate dehydrogenase in phosphate buffer at pH 7.5 has been studied by equilibrium and kinetic methods. Hyperbolic binding was obtained by fluorimetric titration of enzyme with NADH, in the presence or absence of hydroxymalonate. Identical results were obtained for titrations of NADH with enzyme in the presence or absence of hydroxymalonate, measured either by fluorescence emission intensity or by the product of intensity and anisotropy. The equilibrium constant for NADH dissociation was 3.8 +/- 0.2 micrometers, over a 23-fold range of enzyme concentration, and the value in the presence of saturating hydroxymalonate was 0.33 +/- 0.02 micrometer over a 10-fold range of enzyme concentration. The rate constant for NADH binding to the enzyme in the presence of hydroxymalonate was 3.6 X 10(7) M-1 s-1, while the value for dissociation from the ternary complex was 30 +/- 1 s-1. No limiting binding rate was obtained at pseudo-first order rate constants as high as 200 s-1, and the rate curve for dissociation was a single exponential for at least 98% of the amplitude. In addition to demonstrating that the binding sites are independent and indistinguishable, the absence of effects of enzyme concentration on the KD value indicates that NADH binds with equal affinity to monomeric and dimeric enzyme forms.", "contents": "NADH binding to porcine mitochondrial malate dehydrogenase. The binding of NADH to porcine mitochondrial malate dehydrogenase in phosphate buffer at pH 7.5 has been studied by equilibrium and kinetic methods. Hyperbolic binding was obtained by fluorimetric titration of enzyme with NADH, in the presence or absence of hydroxymalonate. Identical results were obtained for titrations of NADH with enzyme in the presence or absence of hydroxymalonate, measured either by fluorescence emission intensity or by the product of intensity and anisotropy. The equilibrium constant for NADH dissociation was 3.8 +/- 0.2 micrometers, over a 23-fold range of enzyme concentration, and the value in the presence of saturating hydroxymalonate was 0.33 +/- 0.02 micrometer over a 10-fold range of enzyme concentration. The rate constant for NADH binding to the enzyme in the presence of hydroxymalonate was 3.6 X 10(7) M-1 s-1, while the value for dissociation from the ternary complex was 30 +/- 1 s-1. No limiting binding rate was obtained at pseudo-first order rate constants as high as 200 s-1, and the rate curve for dissociation was a single exponential for at least 98% of the amplitude. In addition to demonstrating that the binding sites are independent and indistinguishable, the absence of effects of enzyme concentration on the KD value indicates that NADH binds with equal affinity to monomeric and dimeric enzyme forms."}
{"id": "PMID:225322", "title": "Nucleoside diphosphate kinase activity in purified cores of vesicular stomatitis virus.", "content": "Purified cores of vesicular stomatitis virus contain an enzymatic activity that converts GDP, UDP, and CDP into their corresponding triphosphates using ATP as the phosphate donor. Thus, the virion-associated RNA polymerase can synthesize mRNA normally in vitro even when one of the ribonucleoside triphosphates is replaced by its corresponding diphosphate. RNA synthesis does not proceed if ATP is replaced by ADP. Similarly RNA synthesis is impaired if CDP and UDP are present in the same reaction. The role of the nucleoside diphosphate kinase (NDP kinase, EC 2.7.4.6) in vesicular stomatitis virus mRNA synthesis in vitro is discussed.", "contents": "Nucleoside diphosphate kinase activity in purified cores of vesicular stomatitis virus. Purified cores of vesicular stomatitis virus contain an enzymatic activity that converts GDP, UDP, and CDP into their corresponding triphosphates using ATP as the phosphate donor. Thus, the virion-associated RNA polymerase can synthesize mRNA normally in vitro even when one of the ribonucleoside triphosphates is replaced by its corresponding diphosphate. RNA synthesis does not proceed if ATP is replaced by ADP. Similarly RNA synthesis is impaired if CDP and UDP are present in the same reaction. The role of the nucleoside diphosphate kinase (NDP kinase, EC 2.7.4.6) in vesicular stomatitis virus mRNA synthesis in vitro is discussed."}
{"id": "PMID:225324", "title": "Partial characterization of a glycoprotein comprising the NH2-terminal region of mouse tumor cell pro-adrenocorticotropic hormone/endorphin.", "content": "The glycoprotein accounting for most of the nonadrenocorticotropic hormone (ACTH), non-beta-lipotropin (beta LPH) region of mouse tumor cell pro-ACTH/endorphin was purified from tumor cell culture medium and shown to contain 1/2 cystine residues. Preparations of the 16,000-dalton fragment-related material (referred to as 16K fragment) were heterogeneous with respect to size and charge. Despite this heterogeneity, a partial amino acid sequence for the NH2-terminal region of the molecule was determined by automated Edman degradationof the 16K fragment labeled by reduction and alkylation with [3H]iodoacetic acid or labeled biosynthetically with [3H]tryptophan. The sequence of 1/2 cystine and tryptophan residues in the mouse tumor 16K fragment can be aligned with one region of the amino acid sequence predicted from the cDNA for a bovine precursor to ACTH/beta LPH (Nakanishi, S., Inoue, A., Kita, T., Nakamura, M., Chang, A.C.Y., Cohen, S.N., and Numa, S. (1979) Nature 278, 423--427).", "contents": "Partial characterization of a glycoprotein comprising the NH2-terminal region of mouse tumor cell pro-adrenocorticotropic hormone/endorphin. The glycoprotein accounting for most of the nonadrenocorticotropic hormone (ACTH), non-beta-lipotropin (beta LPH) region of mouse tumor cell pro-ACTH/endorphin was purified from tumor cell culture medium and shown to contain 1/2 cystine residues. Preparations of the 16,000-dalton fragment-related material (referred to as 16K fragment) were heterogeneous with respect to size and charge. Despite this heterogeneity, a partial amino acid sequence for the NH2-terminal region of the molecule was determined by automated Edman degradationof the 16K fragment labeled by reduction and alkylation with [3H]iodoacetic acid or labeled biosynthetically with [3H]tryptophan. The sequence of 1/2 cystine and tryptophan residues in the mouse tumor 16K fragment can be aligned with one region of the amino acid sequence predicted from the cDNA for a bovine precursor to ACTH/beta LPH (Nakanishi, S., Inoue, A., Kita, T., Nakamura, M., Chang, A.C.Y., Cohen, S.N., and Numa, S. (1979) Nature 278, 423--427)."}
{"id": "PMID:225327", "title": "Assembly of the mitochondrial membrane system. DNA sequence of subunit 2 of yeast cytochrome oxidase.", "content": "A cytoplasmic \"petitie\" mutant of Saccharomyces cerevisiae (DS200/A1) has been isolated and determined to contain mitochondrial genetic markers in the oxi 1 locus. This locus has previously been reported to code for the structural gene of subunit 2 of cytochrome oxidase (Cabral et al. (1978) J. Biol. Chem. 243, 297-304). The segment of mitochondrial DNA retained in DS200/A1 has a repeat length of approximately 4500 base pairs and based on DNA sequencing contains a 756-nucleotide-long sequence that has been identified as the structural gene of subunit 2 of cytochrome oxidase. The presumptive gene sequence generates an amino acid sequence consistent with the reported molecular weight and composition of subunit 2 of yeast cytochrome oxidase. The correctness of the deduced amino acid sequence is further supported by its extensive homology to the primary structure of bovine cytochrome oxidase. The DNA segment of DS200/A1 has been located on the wild type mitochondrial DNA by comparative restriction mapping. The orientation of the COOH and NH2 termini and the direction of transcription of the gene have been determined.", "contents": "Assembly of the mitochondrial membrane system. DNA sequence of subunit 2 of yeast cytochrome oxidase. A cytoplasmic \"petitie\" mutant of Saccharomyces cerevisiae (DS200/A1) has been isolated and determined to contain mitochondrial genetic markers in the oxi 1 locus. This locus has previously been reported to code for the structural gene of subunit 2 of cytochrome oxidase (Cabral et al. (1978) J. Biol. Chem. 243, 297-304). The segment of mitochondrial DNA retained in DS200/A1 has a repeat length of approximately 4500 base pairs and based on DNA sequencing contains a 756-nucleotide-long sequence that has been identified as the structural gene of subunit 2 of cytochrome oxidase. The presumptive gene sequence generates an amino acid sequence consistent with the reported molecular weight and composition of subunit 2 of yeast cytochrome oxidase. The correctness of the deduced amino acid sequence is further supported by its extensive homology to the primary structure of bovine cytochrome oxidase. The DNA segment of DS200/A1 has been located on the wild type mitochondrial DNA by comparative restriction mapping. The orientation of the COOH and NH2 termini and the direction of transcription of the gene have been determined."}
{"id": "PMID:225333", "title": "Fibrosarcomata and malignant fibrous histiocytomata arising in relation to enchondromata.", "content": "Six cases are reported in which a fibrosarcoma or malignant fibrous histiocytoma developed in relation to an enchondroma in a long bone. Four of the tumours were fibrosarcomata, and two were malignant fibrous histiocytomata. Five of the six cases were in the distal femur, which is a common site for old calcified enchondromata or \"cartilage rests\". The age of the patients was between fifty-six and eighty-six with a mean of seventy. Four were women, Five died less than one year after presentation. The fibrosarcomata and malignant fibrous histiocytomata do not appear to have arisen directly from the tumour cartilage but from the dense fibrous tissue surrounding necrotic areas in the enchondromata by a process analogous to that responsible for the development of fibrosarcomata in bone infarcts and chronic osteomyelitis. The possibility that some \"dedifferentiated\" chondrosarcomata are forms of collision tumour is discussed.", "contents": "Fibrosarcomata and malignant fibrous histiocytomata arising in relation to enchondromata. Six cases are reported in which a fibrosarcoma or malignant fibrous histiocytoma developed in relation to an enchondroma in a long bone. Four of the tumours were fibrosarcomata, and two were malignant fibrous histiocytomata. Five of the six cases were in the distal femur, which is a common site for old calcified enchondromata or \"cartilage rests\". The age of the patients was between fifty-six and eighty-six with a mean of seventy. Four were women, Five died less than one year after presentation. The fibrosarcomata and malignant fibrous histiocytomata do not appear to have arisen directly from the tumour cartilage but from the dense fibrous tissue surrounding necrotic areas in the enchondromata by a process analogous to that responsible for the development of fibrosarcomata in bone infarcts and chronic osteomyelitis. The possibility that some \"dedifferentiated\" chondrosarcomata are forms of collision tumour is discussed."}
{"id": "PMID:225334", "title": "Adrenocorticotropin and beta-lipotropin in the hypothalamus. Localization in the same arcuate neurons by sequential immunocytochemical procedures.", "content": "Adrenocorticotropin and beta-lipotropin (beta-LPH) have been localized by immunoperoxidase methods in nerve cells and fibers of the hypothalamus and brain stem of the ewe. 6-mum sections were immunostained first for either ACTH or beta-LPH. The reaction products and the antibody complexes were then eluted completely from the tissue, and the same section was immunostained for the second peptide. Absorption of the primary antisera with a variety of peptide fragments of ACTH and beta-LPH demonstrated, immunocytochemically as well as by radioimmunoassay, that the ACTH and beta-LPH antisera were directed to the COOH- and NH(2)-termini of the peptides, respectively. Neither antiserum recognized any portion of the heterologous peptide. In the sequential staining procedure on the same tissue section, preincubation of the antisera with the homologous peptide abolished the staining, whereas preincubation with the heterologous peptide did not affect it, regardless of the order followed. Every nerve cell in the arcuate nucleus that contained ACTH also contained beta-LPH, but beta-LPH cells appeared, probably falsely, to be twice as numerous as ACTH cells. beta-LPH-positive fibers in and beyond the hypothalamus were also more numerous and stained more intensively than ACTH fibers. The salient exception was fibers in the infundibular zona externa, where the opposite was true. Our observations establish that ACTH and beta-LPH are contained in the same nerve cells They stongly favor biosynthesis in brain, probably from a common precursor molecule, as has been demonstrated in the pituitary gland. The complexity of the cytologic distribution pattern described suggests that the two peptides are not processed in the same manner by the nerve cell.", "contents": "Adrenocorticotropin and beta-lipotropin in the hypothalamus. Localization in the same arcuate neurons by sequential immunocytochemical procedures. Adrenocorticotropin and beta-lipotropin (beta-LPH) have been localized by immunoperoxidase methods in nerve cells and fibers of the hypothalamus and brain stem of the ewe. 6-mum sections were immunostained first for either ACTH or beta-LPH. The reaction products and the antibody complexes were then eluted completely from the tissue, and the same section was immunostained for the second peptide. Absorption of the primary antisera with a variety of peptide fragments of ACTH and beta-LPH demonstrated, immunocytochemically as well as by radioimmunoassay, that the ACTH and beta-LPH antisera were directed to the COOH- and NH(2)-termini of the peptides, respectively. Neither antiserum recognized any portion of the heterologous peptide. In the sequential staining procedure on the same tissue section, preincubation of the antisera with the homologous peptide abolished the staining, whereas preincubation with the heterologous peptide did not affect it, regardless of the order followed. Every nerve cell in the arcuate nucleus that contained ACTH also contained beta-LPH, but beta-LPH cells appeared, probably falsely, to be twice as numerous as ACTH cells. beta-LPH-positive fibers in and beyond the hypothalamus were also more numerous and stained more intensively than ACTH fibers. The salient exception was fibers in the infundibular zona externa, where the opposite was true. Our observations establish that ACTH and beta-LPH are contained in the same nerve cells They stongly favor biosynthesis in brain, probably from a common precursor molecule, as has been demonstrated in the pituitary gland. The complexity of the cytologic distribution pattern described suggests that the two peptides are not processed in the same manner by the nerve cell."}
{"id": "PMID:225335", "title": "Regulation of secretion of parathormone and secretory protein-I from separate intracellular pools by calcium, dibutyryl cyclic AMP, and (1)-isoproterenol.", "content": "Dispersed porcine parathyroid cells were incubated at calcium concentrations between 0.5 and 3.0 mM in the presence of 3H- or 14C-amino acids to label newly synthesized parathormone. Up to four times more hormone was secreted at the lower calcium concentration but its specific radioactivity, from 30 to 50 times that of the intracellular pool, did not change. Dibutyrl cyclic AMP doubled immunoactive parathormone secretion at each calcium concentration, but there was no increase in secretion of radioactive hormone if labeled amino acids and secretagogue were added simultaneously. Similarly, when the intracellular pool of parathormone was prelabeled with 3H-amino acids and then the cells were incubated in 14C-amino acids and dibutyryl cyclic AMP, the entire increase in hormone secreted was derived from the prelabeled pool. (1)-isoproterenol increased intracellular cyclic AMP and acted on hormone secretion in a manner indistinguishable from dibutyryl cyclic AMP. In similar double-label experiments dibutyryl cyclic AMP preferentially enhanced secretion of secretory protein-I, a calcium-regulated protein of the parathyroid of unknown function. Calcium, alone, inhibited the intracellular level of cyclic AMP in a concentration-dependent fashion. These data are consistent with the existence in the parathyroid cell preparation of two hormone and secretory protein pools that may be individually recruitable--one consisting of most recently synthesized protein, the other consisting of older \"storage\" protein. The data do not allow one to decide whether the two pools coexist within individual cells or whether, instead, they exist in separate cells of the dispersed gland preparation.", "contents": "Regulation of secretion of parathormone and secretory protein-I from separate intracellular pools by calcium, dibutyryl cyclic AMP, and (1)-isoproterenol. Dispersed porcine parathyroid cells were incubated at calcium concentrations between 0.5 and 3.0 mM in the presence of 3H- or 14C-amino acids to label newly synthesized parathormone. Up to four times more hormone was secreted at the lower calcium concentration but its specific radioactivity, from 30 to 50 times that of the intracellular pool, did not change. Dibutyrl cyclic AMP doubled immunoactive parathormone secretion at each calcium concentration, but there was no increase in secretion of radioactive hormone if labeled amino acids and secretagogue were added simultaneously. Similarly, when the intracellular pool of parathormone was prelabeled with 3H-amino acids and then the cells were incubated in 14C-amino acids and dibutyryl cyclic AMP, the entire increase in hormone secreted was derived from the prelabeled pool. (1)-isoproterenol increased intracellular cyclic AMP and acted on hormone secretion in a manner indistinguishable from dibutyryl cyclic AMP. In similar double-label experiments dibutyryl cyclic AMP preferentially enhanced secretion of secretory protein-I, a calcium-regulated protein of the parathyroid of unknown function. Calcium, alone, inhibited the intracellular level of cyclic AMP in a concentration-dependent fashion. These data are consistent with the existence in the parathyroid cell preparation of two hormone and secretory protein pools that may be individually recruitable--one consisting of most recently synthesized protein, the other consisting of older \"storage\" protein. The data do not allow one to decide whether the two pools coexist within individual cells or whether, instead, they exist in separate cells of the dispersed gland preparation."}
{"id": "PMID:225336", "title": "Functional changes in human leukemic cell line HL-60. A model for myeloid differentiation.", "content": "Polar solvents induce terminal differentiation in the human promyelocytic leukemia cell line HL-60. The present studies describe the functional changes that accompany the morphologic progression from promyelocytes to bands and poly-morphonuclear leukocytes (PMN) over 9 d of culture in 1.3 percent dimethylsulfoxide (DMSO). As the HL-60 cells mature, the rate of O(2-) production increase 18-fold, with a progressive shortening of the lag time required for activation. Hexosemonophosphate shunt activity rises concomitantly. Ingestin of paraffin oil droplets opsonized with complement or Ig increases 10-fold over 9 d in DMSO. Latex ingestion per cell by each morphologic type does not change significantly, but total latex ingestion by groups of cells increases with the rise in the proportion of mature cells with greater ingestion capacities. Degranulation, as measured by release of beta-glucuronidase, lysozyme, and peroxidase, reaches maximum after 3-6 d in DMSO, then declines. HL-60 cells contain no detectable lactoferrin, suggesting that their secondary granules are absent or defective. However, they kill staphylococci by day 6 in DMSO. Morphologically immature cells (days 1-3 in DMSO) are capable of O(2-) generation, hexosemonophosphate shunt activity, ingestion, degranulation, and bacterial killing. Maximal performance of each function by cells incubated in DMSO for longer periods of time is 50-100 percent that of normal PMN. DMSO- induced differentiation of HL-60 cells is a promising model for myeloid development.", "contents": "Functional changes in human leukemic cell line HL-60. A model for myeloid differentiation. Polar solvents induce terminal differentiation in the human promyelocytic leukemia cell line HL-60. The present studies describe the functional changes that accompany the morphologic progression from promyelocytes to bands and poly-morphonuclear leukocytes (PMN) over 9 d of culture in 1.3 percent dimethylsulfoxide (DMSO). As the HL-60 cells mature, the rate of O(2-) production increase 18-fold, with a progressive shortening of the lag time required for activation. Hexosemonophosphate shunt activity rises concomitantly. Ingestin of paraffin oil droplets opsonized with complement or Ig increases 10-fold over 9 d in DMSO. Latex ingestion per cell by each morphologic type does not change significantly, but total latex ingestion by groups of cells increases with the rise in the proportion of mature cells with greater ingestion capacities. Degranulation, as measured by release of beta-glucuronidase, lysozyme, and peroxidase, reaches maximum after 3-6 d in DMSO, then declines. HL-60 cells contain no detectable lactoferrin, suggesting that their secondary granules are absent or defective. However, they kill staphylococci by day 6 in DMSO. Morphologically immature cells (days 1-3 in DMSO) are capable of O(2-) generation, hexosemonophosphate shunt activity, ingestion, degranulation, and bacterial killing. Maximal performance of each function by cells incubated in DMSO for longer periods of time is 50-100 percent that of normal PMN. DMSO- induced differentiation of HL-60 cells is a promising model for myeloid development."}
{"id": "PMID:225337", "title": "Localization of Na pumps in the tracheal epithelium of the dog.", "content": "Binding of [3H]ouabain by the dog's tracheal epithelium shows a nonspecific component depending linearly on ouabain concentration, and a specific saturable component with a Km of 10(-7) M. Control experiments showed that the tracer taken up was not trapped within the extracellular space nor bound to tissue collagen. Inhibition of the saturable uptake by high K, metabolic inhibition, low Na, and low temperature indicated that binding was to Na/K ATPase. One-sided exposures of tissue sheets to tracer showed that the submucosal side took up 10 X as much tracer as the luminal. Autoradiography localized tracer uptake under all conditions to the cells' basolateral membranes.", "contents": "Localization of Na pumps in the tracheal epithelium of the dog. Binding of [3H]ouabain by the dog's tracheal epithelium shows a nonspecific component depending linearly on ouabain concentration, and a specific saturable component with a Km of 10(-7) M. Control experiments showed that the tracer taken up was not trapped within the extracellular space nor bound to tissue collagen. Inhibition of the saturable uptake by high K, metabolic inhibition, low Na, and low temperature indicated that binding was to Na/K ATPase. One-sided exposures of tissue sheets to tracer showed that the submucosal side took up 10 X as much tracer as the luminal. Autoradiography localized tracer uptake under all conditions to the cells' basolateral membranes."}
{"id": "PMID:225338", "title": "Quantitative biochemical analysis of microtubule content in normal and transformed 3T3 cells.", "content": "Microtubules in normal and transformed BALB 3T3 cells were preserved in a stabilizing medium and measured by a [3H]colchicine-binding tubulin assay, and compared to total cellular tubulin measured under nonstabilizing conditions. Essentially no change in tubulin or microtubule content was seen with changes in cell density or with changes in cellular morphology at various stages of growth of normal or transformed cells or induced by dibutyryl cAMP treatment of transformed cells. Of five cell lines transformed by a variety of agents, four had a significantly higher total tubulin content than untransformed 3T3 cells and all of them had an increased microtubule content. None of the transformed lines had a lower fraction of tubulin recoverable as sedimentable microtubules compared to untransformed cells, and in three of them this fraction was significantly higher. These results establish that microtubules are present in transformed cells to at least the extent (if not greater) than in normal cells but that there are variations in the total amount of tubulin and microtubules as well as the fraction of the total tubulin present as microtubules which are not strictly correlated with transformation or cell morphology.", "contents": "Quantitative biochemical analysis of microtubule content in normal and transformed 3T3 cells. Microtubules in normal and transformed BALB 3T3 cells were preserved in a stabilizing medium and measured by a [3H]colchicine-binding tubulin assay, and compared to total cellular tubulin measured under nonstabilizing conditions. Essentially no change in tubulin or microtubule content was seen with changes in cell density or with changes in cellular morphology at various stages of growth of normal or transformed cells or induced by dibutyryl cAMP treatment of transformed cells. Of five cell lines transformed by a variety of agents, four had a significantly higher total tubulin content than untransformed 3T3 cells and all of them had an increased microtubule content. None of the transformed lines had a lower fraction of tubulin recoverable as sedimentable microtubules compared to untransformed cells, and in three of them this fraction was significantly higher. These results establish that microtubules are present in transformed cells to at least the extent (if not greater) than in normal cells but that there are variations in the total amount of tubulin and microtubules as well as the fraction of the total tubulin present as microtubules which are not strictly correlated with transformation or cell morphology."}
{"id": "PMID:225339", "title": "Dibutyryl cyclic AMP suppresses mobility of embryonic chick heart cells in aggregates.", "content": "The intermixing of chick embryonic heart ventricle cells was studied in cellular aggregates as a function of embryonic age of the cells. Cell mobility, as measured by intermixing of radiolabelled and unlabelled cells, was high in cells derived from young embryos: 5.36 +/- 1.05 cell diameters per 2.5 days for 6-day-old heart ventricle cells. During development, mobility steadily declined to 1.56 +/- 0.24 cell diameters per 2.5 days for 18-day old cells. Treatment of aggregates with 1.0 mM theophylline plus 1.2 mM dibutyryl cyclic AMP resulted in greatly decreased mobility, particularly in aggregates of the more mobile younger cells. Depending on the embryonic age of the heart ventricle cells, this treatment reduced mobility by 45.3 to 89.4%. These data are consistent with an age-dependent decrease in intrinsic mobility superimposed upon a contact-paralysis mediated inhibition of movement present in solid tissues. In addition, the sensitivity of heart ventricle cells to inhibition by agents that increase intracellular cyclic AMP levels suggest that this is another possible inhibitory mechanism, although its physiological significance has not been established.", "contents": "Dibutyryl cyclic AMP suppresses mobility of embryonic chick heart cells in aggregates. The intermixing of chick embryonic heart ventricle cells was studied in cellular aggregates as a function of embryonic age of the cells. Cell mobility, as measured by intermixing of radiolabelled and unlabelled cells, was high in cells derived from young embryos: 5.36 +/- 1.05 cell diameters per 2.5 days for 6-day-old heart ventricle cells. During development, mobility steadily declined to 1.56 +/- 0.24 cell diameters per 2.5 days for 18-day old cells. Treatment of aggregates with 1.0 mM theophylline plus 1.2 mM dibutyryl cyclic AMP resulted in greatly decreased mobility, particularly in aggregates of the more mobile younger cells. Depending on the embryonic age of the heart ventricle cells, this treatment reduced mobility by 45.3 to 89.4%. These data are consistent with an age-dependent decrease in intrinsic mobility superimposed upon a contact-paralysis mediated inhibition of movement present in solid tissues. In addition, the sensitivity of heart ventricle cells to inhibition by agents that increase intracellular cyclic AMP levels suggest that this is another possible inhibitory mechanism, although its physiological significance has not been established."}
{"id": "PMID:225340", "title": "Identification of human anterior pituitary cells by immunoelectron microscopy.", "content": "An attempt was made to classify human pituitary cell types by electron microscopic immunohistochemistry. The immunoperoxidase technique involving the use of the peroxidase-antiperoxidase complex was applied to thin sections of human pituitaries removed surgically for breast cancer or diabetic retinopathy. Using specific antibodies against human PRL, GH, beta-FSH, beta-LH, beta-TSH, and porcine ACTH, the localization of each hormone was studied. Identification of 5 human pituitary cells was possible: 1) The PRL-secreting cell contains round or slightly ovoid secretory granules of a diameter of 275-350 nm. 2) The GH-secreting cell is densely granulated with granule diameters ranging from 350-500 nm. 3) The gonadotrophic cell, which stains for both beta-FSH and beta-LH, is characterized by the presence of a varying number of secretory granules ranging from 275-375 nm. 4) The cortico-lipotrophic cell has numerous granules of about 375-550 nm in diameter. 5) The TSH-secreting cell contains small secretory granules of about 125-200 nm in diameter. Another cell type of which the small secretory granules of about 100 nm in diameter could not be stained by any of the antisera was also observed. This ultrastructural identification of human pituitary cells should contribute to a better understanding of the pathophysiology of the human pituitary.", "contents": "Identification of human anterior pituitary cells by immunoelectron microscopy. An attempt was made to classify human pituitary cell types by electron microscopic immunohistochemistry. The immunoperoxidase technique involving the use of the peroxidase-antiperoxidase complex was applied to thin sections of human pituitaries removed surgically for breast cancer or diabetic retinopathy. Using specific antibodies against human PRL, GH, beta-FSH, beta-LH, beta-TSH, and porcine ACTH, the localization of each hormone was studied. Identification of 5 human pituitary cells was possible: 1) The PRL-secreting cell contains round or slightly ovoid secretory granules of a diameter of 275-350 nm. 2) The GH-secreting cell is densely granulated with granule diameters ranging from 350-500 nm. 3) The gonadotrophic cell, which stains for both beta-FSH and beta-LH, is characterized by the presence of a varying number of secretory granules ranging from 275-375 nm. 4) The cortico-lipotrophic cell has numerous granules of about 375-550 nm in diameter. 5) The TSH-secreting cell contains small secretory granules of about 125-200 nm in diameter. Another cell type of which the small secretory granules of about 100 nm in diameter could not be stained by any of the antisera was also observed. This ultrastructural identification of human pituitary cells should contribute to a better understanding of the pathophysiology of the human pituitary."}
{"id": "PMID:225341", "title": "Plasma aldosterone response to ACTH in primary aldosteronism and in patients with low renin hypertension.", "content": "ACTH alpha 1-24 was infused at incremental rates of 12.5-200 mIU/30 min in dexamethasone-suppressed hypertensive patients on a regular sodium diet. The plasma aldosterone response to this stimulus in 8 patients with hyperaldosteronism due to an adrenal aldenoma and 11 with adrenal hyperplasia was significantly greater at all infusion rates (P less than 0.05) when compared with the response in 6 normal subjects on a similar diet. This responsiveness to ACTH in the patients with primary hyperaldosteronism was similar to that of the normal subjects on a low sodium diet. Twelve patients with low renin and 6 patients with normal renin essential hypertension were similarly studied. There was no significant difference in the median aldosterone response between these 2 groups and the normal subjects on a normal diet, but the response was significantly lower compared with that in patients with primary hyperaldosteronism. These data show that patients with hyperaldosteronism from an adrenal adenoma or hyperplasia have a consistent and exaggerated response to ACTH. The hyper-responsiveness is not apparently shared by the majority of patients with low renin essential hypertension and does not support the concept that this group is an intermediate form of primary aldosteronism. Individual patients within this group, however, may have such a response and might be identified by this type of testing.", "contents": "Plasma aldosterone response to ACTH in primary aldosteronism and in patients with low renin hypertension. ACTH alpha 1-24 was infused at incremental rates of 12.5-200 mIU/30 min in dexamethasone-suppressed hypertensive patients on a regular sodium diet. The plasma aldosterone response to this stimulus in 8 patients with hyperaldosteronism due to an adrenal aldenoma and 11 with adrenal hyperplasia was significantly greater at all infusion rates (P less than 0.05) when compared with the response in 6 normal subjects on a similar diet. This responsiveness to ACTH in the patients with primary hyperaldosteronism was similar to that of the normal subjects on a low sodium diet. Twelve patients with low renin and 6 patients with normal renin essential hypertension were similarly studied. There was no significant difference in the median aldosterone response between these 2 groups and the normal subjects on a normal diet, but the response was significantly lower compared with that in patients with primary hyperaldosteronism. These data show that patients with hyperaldosteronism from an adrenal adenoma or hyperplasia have a consistent and exaggerated response to ACTH. The hyper-responsiveness is not apparently shared by the majority of patients with low renin essential hypertension and does not support the concept that this group is an intermediate form of primary aldosteronism. Individual patients within this group, however, may have such a response and might be identified by this type of testing."}
{"id": "PMID:225342", "title": "Thyroglobulin inhibition of thyrotropin binding to thyroid plasma membrane.", "content": "The effect of thyroglobulin (TG) on binding of TSH to thyroid plasma membranes was studied in vitro. Human and bovine thyroid plasma membranes have specific binding sites for bovine [125I]TSH. The binding of [125I]TSH is inhibited by the addition of purified TG (100 ng/microgram/ml). The inhibitory mechanism appears to be noncompetitive when subjected to Lineweaver-Burk analysis. Incubation of TG with TSH did not show an interaction, as assessed by sucrose gradient centrifugation. Plasma membranes prepared from human thyroid tissue have specific binding sites for human TG, as shown by [125I]TG binding assay. The TG binding was not affected by adding low concentrations of unlabeled bovine TSH. In the presence of very high concentrations of TSH, TG binding was increased. Hemoglobin, beta-lactoglobin, and ovalbumin did not have an inhibitory effect on [125I]TSH and [125I] TG binding to membrane preparations. Both [125I]TSH and [125I]TG binding were inhibited by 10 mM neuraminic acid. These results suggested that 1) TG released from thyroid gland may have a regulatory effect on TSH binding to its specific receptor, and 2) there are specific binding sites for TG on the thyroid plasma membrane.", "contents": "Thyroglobulin inhibition of thyrotropin binding to thyroid plasma membrane. The effect of thyroglobulin (TG) on binding of TSH to thyroid plasma membranes was studied in vitro. Human and bovine thyroid plasma membranes have specific binding sites for bovine [125I]TSH. The binding of [125I]TSH is inhibited by the addition of purified TG (100 ng/microgram/ml). The inhibitory mechanism appears to be noncompetitive when subjected to Lineweaver-Burk analysis. Incubation of TG with TSH did not show an interaction, as assessed by sucrose gradient centrifugation. Plasma membranes prepared from human thyroid tissue have specific binding sites for human TG, as shown by [125I]TG binding assay. The TG binding was not affected by adding low concentrations of unlabeled bovine TSH. In the presence of very high concentrations of TSH, TG binding was increased. Hemoglobin, beta-lactoglobin, and ovalbumin did not have an inhibitory effect on [125I]TSH and [125I] TG binding to membrane preparations. Both [125I]TSH and [125I]TG binding were inhibited by 10 mM neuraminic acid. These results suggested that 1) TG released from thyroid gland may have a regulatory effect on TSH binding to its specific receptor, and 2) there are specific binding sites for TG on the thyroid plasma membrane."}
{"id": "PMID:225343", "title": "Inhibition of leukocyte superoxide anion production by cortisol administration to normal subjects.", "content": "Superoxide anion production was suppressed in leukocytes obtained at two or four hours following oral administration of 50 to 100 mg of cortisol to normal subjects. The suppression lasted at least 4 hours but was not present at 24 hours. The measurement of superoxide anion production by leukocytes appears to be a convenient method for the serial estimation of an important biologic effect of corticosteroids in human subjects.", "contents": "Inhibition of leukocyte superoxide anion production by cortisol administration to normal subjects. Superoxide anion production was suppressed in leukocytes obtained at two or four hours following oral administration of 50 to 100 mg of cortisol to normal subjects. The suppression lasted at least 4 hours but was not present at 24 hours. The measurement of superoxide anion production by leukocytes appears to be a convenient method for the serial estimation of an important biologic effect of corticosteroids in human subjects."}
{"id": "PMID:225344", "title": "Characterization of lipotropin-, corticotropin-, and beta-endorphin-immunoreactive materials secreted in vitro by a human pituitary adenoma responsible for a case of Nelson's syndrome.", "content": "A human pituitary adenoma responsible for a case of Nelson's syndrome was maintained in organ culture and the incubation medium was examined with four different RIAs; human corticotropin (ACTH), beta-MSH, lipotropin (LPH), and beta-endorphin (beta-End). All four immunoreactivites (IRs) were present in the medium obtained after 24 h of incubation. Gel exclusion chromatography under  denaturing conditions (6 m guanidine HCl) revealed several immunoreactive components. Two components having both human beta-MSH (beta-hMSH) and human LPH (hLPH) IR coeluted with beta-hLPH and gamma-hLPH; a component with beta-hMSH IR but no hLPH IR coeluted with [125I]beta-hMSH; a component with human ACTH (hACTH) IR eluted at the position of hACTH. Sephadex G-50 gel exclusion chromatography revealed that approximately 80% and 20% of human beta-End (beta-hEnd) IR were accounted for by components coeluting with beta-hLPH and beta-hEnd, respectively. These data demonstrate the presence in this incubation medium of materials similar to if not identical with beta-hLPH, gamma-hLPH, hACTH, beta-hMSH, and beta-hEnd; they suggest that all of these peptides may be secreted in the circulation of patients with Nelson's syndrome.", "contents": "Characterization of lipotropin-, corticotropin-, and beta-endorphin-immunoreactive materials secreted in vitro by a human pituitary adenoma responsible for a case of Nelson's syndrome. A human pituitary adenoma responsible for a case of Nelson's syndrome was maintained in organ culture and the incubation medium was examined with four different RIAs; human corticotropin (ACTH), beta-MSH, lipotropin (LPH), and beta-endorphin (beta-End). All four immunoreactivites (IRs) were present in the medium obtained after 24 h of incubation. Gel exclusion chromatography under  denaturing conditions (6 m guanidine HCl) revealed several immunoreactive components. Two components having both human beta-MSH (beta-hMSH) and human LPH (hLPH) IR coeluted with beta-hLPH and gamma-hLPH; a component with beta-hMSH IR but no hLPH IR coeluted with [125I]beta-hMSH; a component with human ACTH (hACTH) IR eluted at the position of hACTH. Sephadex G-50 gel exclusion chromatography revealed that approximately 80% and 20% of human beta-End (beta-hEnd) IR were accounted for by components coeluting with beta-hLPH and beta-hEnd, respectively. These data demonstrate the presence in this incubation medium of materials similar to if not identical with beta-hLPH, gamma-hLPH, hACTH, beta-hMSH, and beta-hEnd; they suggest that all of these peptides may be secreted in the circulation of patients with Nelson's syndrome."}
{"id": "PMID:225345", "title": "Roentgenographic contrast agents inhibit triiodothyronine binding to nuclear receptors in vitro.", "content": "The ability of roentgenographic contrast agents to inhibit binding of [125I]T3 to nuclear receptors was studied during incubation of rat liver nuclei or nuclear extracts in vitro and after ip administration of the agents in vivo. Ipodate, iodipamide, iopanoic acid, and diatrizoate inhibited binding of [125I]T3 in vitro. The most potent inhibitor was ipodate, which produced 50% inhibition of binding at 1.2 X 10(-4) M. When given orally in acute in vivo experiments, ipodate did not diminish binding to liver nuclear receptors. Ipodate appeared to inhibit in vivo metabolism of [125I]T3.", "contents": "Roentgenographic contrast agents inhibit triiodothyronine binding to nuclear receptors in vitro. The ability of roentgenographic contrast agents to inhibit binding of [125I]T3 to nuclear receptors was studied during incubation of rat liver nuclei or nuclear extracts in vitro and after ip administration of the agents in vivo. Ipodate, iodipamide, iopanoic acid, and diatrizoate inhibited binding of [125I]T3 in vitro. The most potent inhibitor was ipodate, which produced 50% inhibition of binding at 1.2 X 10(-4) M. When given orally in acute in vivo experiments, ipodate did not diminish binding to liver nuclear receptors. Ipodate appeared to inhibit in vivo metabolism of [125I]T3."}
{"id": "PMID:225346", "title": "Effect of inhibition of prostaglandin synthesis on sympathetic nervous system function in man.", "content": "The effect of inhibition of prostaglandin synthesis by indomethacin on the function of the peripheral sympathetic nervous system was studied in eight normotensive subjects. Sympathetic nervous function was assessed by measurement of plasma norepinephrine, alpha-adrenergic receptor sites on platelet membranes, and urinary excretion of epinephrine and norepinephrine. Treatment with indomethacin for 7 days resulted in significant decreases in basal plasma norepinephrine from 134 +/- 7 to 99 +/- 6 (SEM) pg/ml (P less than 0.01), a 26% decrease. Posturally stimulated norepinephrine concentrations (337 +/- 14 pg/ml in control studies) were 255 +/- 18 pg/ml (P less than 0.02), 25% lower, with indomethacin. Plasma norepinephrine after 5-min compression of hand grip (468 +/- 47 pg/ml in control) was 331 +/- 30 pg/ml (P less than 0.005), 29% lower, with indomethacin. The number of platelet alpha-adrenergic receptor sites did not change with indomethacin, nor did prostaglandin E1-stimulated cAMP production by platelet membranes. In addition, indomethacin produced no change in urinary excretion of norepinephrine or epinephrine. It is suggested that inhibition of prostaglandin synthesis may lead, via baroreceptor feedback, to a decrease in plasma norepinephrine concentration.", "contents": "Effect of inhibition of prostaglandin synthesis on sympathetic nervous system function in man. The effect of inhibition of prostaglandin synthesis by indomethacin on the function of the peripheral sympathetic nervous system was studied in eight normotensive subjects. Sympathetic nervous function was assessed by measurement of plasma norepinephrine, alpha-adrenergic receptor sites on platelet membranes, and urinary excretion of epinephrine and norepinephrine. Treatment with indomethacin for 7 days resulted in significant decreases in basal plasma norepinephrine from 134 +/- 7 to 99 +/- 6 (SEM) pg/ml (P less than 0.01), a 26% decrease. Posturally stimulated norepinephrine concentrations (337 +/- 14 pg/ml in control studies) were 255 +/- 18 pg/ml (P less than 0.02), 25% lower, with indomethacin. Plasma norepinephrine after 5-min compression of hand grip (468 +/- 47 pg/ml in control) was 331 +/- 30 pg/ml (P less than 0.005), 29% lower, with indomethacin. The number of platelet alpha-adrenergic receptor sites did not change with indomethacin, nor did prostaglandin E1-stimulated cAMP production by platelet membranes. In addition, indomethacin produced no change in urinary excretion of norepinephrine or epinephrine. It is suggested that inhibition of prostaglandin synthesis may lead, via baroreceptor feedback, to a decrease in plasma norepinephrine concentration."}
{"id": "PMID:225347", "title": "Dissociation of cortisol and adrenal androgen secretion in patients with secondary adrenal insufficiency.", "content": "Plasma cortisol, dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), and androstenedione (delta4-A) were measured by RIA during ACTH infusion in preadrenarchal children with constitutional short stature, normal adults, and patients with secondary adrenal insufficiency resulting from hypothalamic-pituitary disease or corticosteroid therapy. The plasma levels of all four steroids were decreased in patients with secondary adrenal insufficiency compared to normal adults, but the decrease in DHA and DHAS was considerably greater than that in cortisol and delta4-A, resulting in significant decreases in the plasma ratios of DHA to cortisol, DHAS to cortisol, DHA to delta4-A, and DHAS to delta4-A (P less than 0.00001). The decreased DHA and DHAS responses to ACTH persisted in one glucocorticoid-treated patient after glucocorticoid therapy was terminated and the cortisol response to ACTH had normalized. The data suggest that adrenal atrophy due to hypothalamic-pituitary disease or corticosteroid therapy is associated with a greater impairment in the secretion of the delta5 adrenal androgens DHA and DHAS than in the secretion of cortisol and delta4-A, and that the capacity to secrete cortisol and delta4-A recovers more rapidly than the capacity to secrete the delta5 adrenal androgens when corticosteroid therapy is withdrawn.", "contents": "Dissociation of cortisol and adrenal androgen secretion in patients with secondary adrenal insufficiency. Plasma cortisol, dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), and androstenedione (delta4-A) were measured by RIA during ACTH infusion in preadrenarchal children with constitutional short stature, normal adults, and patients with secondary adrenal insufficiency resulting from hypothalamic-pituitary disease or corticosteroid therapy. The plasma levels of all four steroids were decreased in patients with secondary adrenal insufficiency compared to normal adults, but the decrease in DHA and DHAS was considerably greater than that in cortisol and delta4-A, resulting in significant decreases in the plasma ratios of DHA to cortisol, DHAS to cortisol, DHA to delta4-A, and DHAS to delta4-A (P less than 0.00001). The decreased DHA and DHAS responses to ACTH persisted in one glucocorticoid-treated patient after glucocorticoid therapy was terminated and the cortisol response to ACTH had normalized. The data suggest that adrenal atrophy due to hypothalamic-pituitary disease or corticosteroid therapy is associated with a greater impairment in the secretion of the delta5 adrenal androgens DHA and DHAS than in the secretion of cortisol and delta4-A, and that the capacity to secrete cortisol and delta4-A recovers more rapidly than the capacity to secrete the delta5 adrenal androgens when corticosteroid therapy is withdrawn."}
{"id": "PMID:225348", "title": "FSH stimulation of 3H-glucosamine-incorporation into proteoglycans by porcine granulosa cells in vitro.", "content": "Porcine granulosa cells from small follicles were incubated in the presence of 1 muCi/ml 3H-glucosamine and various hormones. Proteoglycans were digested with protease, and the mucopolysaccharides (MPS) were recovered. Most of the labeled MPS was found in secretory products. Maximum incorporation of 3H-glucosamine into MPS occurred after incubation with FSH for 8--16 h. Cell concentrations of 0.5--4.0 x 10(6)/ml proved to be ample. Highly purified porcine or human FSH gave consistent, significant stimulation by doses in the order of 100 pg/ml. Linear log-dose response curves occurred from 0.1 to 10.0 ng/ml, and maximal stimulation at 10 ng/ml was 22-fold above control. Preparations of hCG, hTSH and NIH-LH-S18 were not effective. Incubations with 1--10 mM dibutyryl cyclic AMP significantly increased incorporation into MPS, suggesting that effects of FSH may be mediated by cyclic AMP.", "contents": "FSH stimulation of 3H-glucosamine-incorporation into proteoglycans by porcine granulosa cells in vitro. Porcine granulosa cells from small follicles were incubated in the presence of 1 muCi/ml 3H-glucosamine and various hormones. Proteoglycans were digested with protease, and the mucopolysaccharides (MPS) were recovered. Most of the labeled MPS was found in secretory products. Maximum incorporation of 3H-glucosamine into MPS occurred after incubation with FSH for 8--16 h. Cell concentrations of 0.5--4.0 x 10(6)/ml proved to be ample. Highly purified porcine or human FSH gave consistent, significant stimulation by doses in the order of 100 pg/ml. Linear log-dose response curves occurred from 0.1 to 10.0 ng/ml, and maximal stimulation at 10 ng/ml was 22-fold above control. Preparations of hCG, hTSH and NIH-LH-S18 were not effective. Incubations with 1--10 mM dibutyryl cyclic AMP significantly increased incorporation into MPS, suggesting that effects of FSH may be mediated by cyclic AMP."}
{"id": "PMID:225349", "title": "Isolation of oxidase-negative Pseudomonas aeruginosa from sputum culture.", "content": "Two isolates of Pseudomonas aeruginosa lacking characteristic indophenol oxidase were recovered from a sputum specimen. A discussion of the characteristic biochemical tests and antibiograms along with a possible explanation for this phenomenon is presented.", "contents": "Isolation of oxidase-negative Pseudomonas aeruginosa from sputum culture. Two isolates of Pseudomonas aeruginosa lacking characteristic indophenol oxidase were recovered from a sputum specimen. A discussion of the characteristic biochemical tests and antibiograms along with a possible explanation for this phenomenon is presented."}
{"id": "PMID:225350", "title": "Functional profile of the isolated uremic nephron: potassium adaptation in the rabbit cortical collecting tubule.", "content": "As a renal function declines in patients and experimental animals with chronic renal disease, potassium homeostasis is maintained by a progressive increase in potassium secretion by the surviving nephrons, a phenomenon known as potassium adaptation. To determine the nephron site and the underlying mechanisms responsible for this phenomenon, studies were performed on normal and 75% nephrectomized rabbits maintained on normal or high-potassium diets. Cortical collecting tubules (CCT) were dissected from the normal and remnant kidneys and perfused in vitro in an artificial solution. In normal CCT mean (+/- SE) net K secretion, JK, (peq/cm per s) was 1.26 +/- 0.43 (normal diet) and 3.27 +/- 0.66 (high-K diet). In uremic CCT, JK was 3.55 +/- 0.60 (normal diet) and 6.83 +/- 0.58 (high-K diet). By reducing the dietary intake of potassium in proportion to the reduction of renal mass in these uremic animals, the adaptation in K secretion was prevented (JK: 1.22 +/- 0.40). Transepithelial potential difference was similar in CCT from normal and uremic animals on a normal diet despite the fact that JK was significantly greater in the latter group. However, in both normal and uremic CCT, the increase in JK caused by potassium loading was associated with an increase in luminal negativity. Uremic CCT underwent significant compensatory hypertrophy regardless of the dietary intake or potassium secretory rates. Plasma aldosterone levels were elevated only in the uremic-high potassium rabbits suggesting that a mineralocorticoid effect on the CCT may be exaggerated when potassium loading is superimposed upon decreased excretory capacity. The activity of Na-K ATPase was comparable in normal and uremic CCT from rabbits on either normal or high-K diets indicating that potassium adaptation may occur independently of changes in the activity of this enzyme. Intracellular potassium content measured chemically and by 42K exchange, was not significantly altered in either normal or uremic CCT when dietary potassium intake was increased, despite the fact the JK was increased under these circumstances. These data indicate that the CCT is an important site of potassium adaptation in the surviving nephrons of animals with reduced renal mass. This adaptation is an intrinsic property of the CCT and is expressed in the absence of a uremic milieu. Potassium adaptation by the uremic CCT is not fixed according to the degree of compensatory hypertrophy but varies according to the excretory requirements of the animal. Transepithelial potential difference and circulating aldosterone levels contribute to the adaptation but neither factor can entirely account for the phenomenon. Potassium adaptation by the CCT occurs in the absence of changes in Na-K ATPase activity and intracellular potassium content.", "contents": "Functional profile of the isolated uremic nephron: potassium adaptation in the rabbit cortical collecting tubule. As a renal function declines in patients and experimental animals with chronic renal disease, potassium homeostasis is maintained by a progressive increase in potassium secretion by the surviving nephrons, a phenomenon known as potassium adaptation. To determine the nephron site and the underlying mechanisms responsible for this phenomenon, studies were performed on normal and 75% nephrectomized rabbits maintained on normal or high-potassium diets. Cortical collecting tubules (CCT) were dissected from the normal and remnant kidneys and perfused in vitro in an artificial solution. In normal CCT mean (+/- SE) net K secretion, JK, (peq/cm per s) was 1.26 +/- 0.43 (normal diet) and 3.27 +/- 0.66 (high-K diet). In uremic CCT, JK was 3.55 +/- 0.60 (normal diet) and 6.83 +/- 0.58 (high-K diet). By reducing the dietary intake of potassium in proportion to the reduction of renal mass in these uremic animals, the adaptation in K secretion was prevented (JK: 1.22 +/- 0.40). Transepithelial potential difference was similar in CCT from normal and uremic animals on a normal diet despite the fact that JK was significantly greater in the latter group. However, in both normal and uremic CCT, the increase in JK caused by potassium loading was associated with an increase in luminal negativity. Uremic CCT underwent significant compensatory hypertrophy regardless of the dietary intake or potassium secretory rates. Plasma aldosterone levels were elevated only in the uremic-high potassium rabbits suggesting that a mineralocorticoid effect on the CCT may be exaggerated when potassium loading is superimposed upon decreased excretory capacity. The activity of Na-K ATPase was comparable in normal and uremic CCT from rabbits on either normal or high-K diets indicating that potassium adaptation may occur independently of changes in the activity of this enzyme. Intracellular potassium content measured chemically and by 42K exchange, was not significantly altered in either normal or uremic CCT when dietary potassium intake was increased, despite the fact the JK was increased under these circumstances. These data indicate that the CCT is an important site of potassium adaptation in the surviving nephrons of animals with reduced renal mass. This adaptation is an intrinsic property of the CCT and is expressed in the absence of a uremic milieu. Potassium adaptation by the uremic CCT is not fixed according to the degree of compensatory hypertrophy but varies according to the excretory requirements of the animal. Transepithelial potential difference and circulating aldosterone levels contribute to the adaptation but neither factor can entirely account for the phenomenon. Potassium adaptation by the CCT occurs in the absence of changes in Na-K ATPase activity and intracellular potassium content."}
{"id": "PMID:225351", "title": "Regulation of primate testicular luteinizing hormone receptors and steroidogenesis.", "content": "The testicular luteinizing hormone (LH) receptors of the rhesus monkey and human have many features in common, including high equilibrium association constant, marked species specificity, and relatively low binding capacity. We have, therefore, used rhesus monkeys as models for human LH-receptor regulation in vivo during gonadotropin treatment. In four adult male monkeys, treated with 10,000 IU human chorionic gonadotropin (hCG), serum and testicular steroidogenic responses were monitored at 24-h intervals during the following 4 d, and LH-receptor concentrations were measured by (125)I-hCG binding to 15,000-g particles prepared from testis biopsy specimens. In treated animals, serum hCG was maximal on day 1 at 322+/-16 ng/ml and declined to 24.4+/-2.3 ng/ml by day 4. Serum testosterone was increased threefold during the subsequent 4 d (from 6.5+/-2.0 to 18.6+/-4.4 ng/ml) but serum progesterone remained unchanged. In contrast, serum 17alpha-hydroxyprogesterone increased 12-fold to 5.5+/-0.5 ng/ml at day 1 and was increased fourfold during the subsequent 3 d. The LH-receptor binding capacity of the primate testis was reduced by 18.3+/-6.0% on day 1, 51.7+/-7.4% on day 2, and 45.3+/-2.4% on day 4. Occupancy of the LH receptors by endogenously bound hCG was significant on day 1 but was negligible by day 4. These data demonstrate that gonadotropin-induced LH-receptor depletion occurs in the rhesus testis and indicate that primate gonadotropin receptors are susceptible to the regulatory processes recently described in the rat. In addition, the simultaneous and disproportionate accumulation of 17alpha-hydroxyprogesterone indicates that 17,20-desmolase was rate-limiting under these conditions in the primate testis Leydig cell.", "contents": "Regulation of primate testicular luteinizing hormone receptors and steroidogenesis. The testicular luteinizing hormone (LH) receptors of the rhesus monkey and human have many features in common, including high equilibrium association constant, marked species specificity, and relatively low binding capacity. We have, therefore, used rhesus monkeys as models for human LH-receptor regulation in vivo during gonadotropin treatment. In four adult male monkeys, treated with 10,000 IU human chorionic gonadotropin (hCG), serum and testicular steroidogenic responses were monitored at 24-h intervals during the following 4 d, and LH-receptor concentrations were measured by (125)I-hCG binding to 15,000-g particles prepared from testis biopsy specimens. In treated animals, serum hCG was maximal on day 1 at 322+/-16 ng/ml and declined to 24.4+/-2.3 ng/ml by day 4. Serum testosterone was increased threefold during the subsequent 4 d (from 6.5+/-2.0 to 18.6+/-4.4 ng/ml) but serum progesterone remained unchanged. In contrast, serum 17alpha-hydroxyprogesterone increased 12-fold to 5.5+/-0.5 ng/ml at day 1 and was increased fourfold during the subsequent 3 d. The LH-receptor binding capacity of the primate testis was reduced by 18.3+/-6.0% on day 1, 51.7+/-7.4% on day 2, and 45.3+/-2.4% on day 4. Occupancy of the LH receptors by endogenously bound hCG was significant on day 1 but was negligible by day 4. These data demonstrate that gonadotropin-induced LH-receptor depletion occurs in the rhesus testis and indicate that primate gonadotropin receptors are susceptible to the regulatory processes recently described in the rat. In addition, the simultaneous and disproportionate accumulation of 17alpha-hydroxyprogesterone indicates that 17,20-desmolase was rate-limiting under these conditions in the primate testis Leydig cell."}
{"id": "PMID:225352", "title": "Phenobarbital-induced alterations in the metabolism of [3H]vitamin D3 by the perfused rachitic rat liver in vitro.", "content": "Anticonvulsant therapy of seizure disorders in man is associated with the development of complications involving bone and mineral metabolism including hypocalcemia, elevated serum immunoreactive parathyroid hormone levels, and increased amounts of unmineralized bone or osteoid. The latter has been attributed to a reduction in serum-25-hydroxycholecalciferol levels resulting from increased hepatic metabolism of vitamin D. Using an in vitro recycling hepatic perfusion system, we have demonstrated that 5 d of phenobarbital treatment increases the hepatic production of [(3)H]25-hydroxyvitamin D(3) (4.3+/-0.3 vs. 3.3+/-0.2%/h, P <0.025) without affecting the biliary excretion of radioactivity. Furthermore, rachitic livers perfused with blood obtained from animals treated with phenobarbital for 5 d also manifested an increase in [(3)H]25-hydroxyvitamin D(3) production (4.6+/-0.5 vs. 3.3+/-0.2%/h, P < 0.02). Addition of phenobarbital or its major metabolite, p-hydroxyphenobarbital, directly to the perfusion apparatus had no effect on [(3)H]25-hydroxyvitamin D(3) production. Phenobarbital treatment was also attended by a decrease in the intrahepatic content of [(3)H]vitamin D(3) (11.7+/-0.4 vs. 17.5+/-0.7 dpm/mg liver protein, P < 0.001) without alterations in the content of [(3)H]25-hydroxyvitamin D(3). The data collectively suggest that the increased hepatic conversion of [(3)H]vitamin D(3) to [(3)H]25-hydroxyvitamin D(3) attending phenobarbital treatment is secondary to stimulation of the hepatic 25-hydroxylation system(s) by a metabolite of phenobarbital other than p-hydroxyphenobarbital and/or by metabolic alterations resulting from phenobarbital therapy.", "contents": "Phenobarbital-induced alterations in the metabolism of [3H]vitamin D3 by the perfused rachitic rat liver in vitro. Anticonvulsant therapy of seizure disorders in man is associated with the development of complications involving bone and mineral metabolism including hypocalcemia, elevated serum immunoreactive parathyroid hormone levels, and increased amounts of unmineralized bone or osteoid. The latter has been attributed to a reduction in serum-25-hydroxycholecalciferol levels resulting from increased hepatic metabolism of vitamin D. Using an in vitro recycling hepatic perfusion system, we have demonstrated that 5 d of phenobarbital treatment increases the hepatic production of [(3)H]25-hydroxyvitamin D(3) (4.3+/-0.3 vs. 3.3+/-0.2%/h, P <0.025) without affecting the biliary excretion of radioactivity. Furthermore, rachitic livers perfused with blood obtained from animals treated with phenobarbital for 5 d also manifested an increase in [(3)H]25-hydroxyvitamin D(3) production (4.6+/-0.5 vs. 3.3+/-0.2%/h, P < 0.02). Addition of phenobarbital or its major metabolite, p-hydroxyphenobarbital, directly to the perfusion apparatus had no effect on [(3)H]25-hydroxyvitamin D(3) production. Phenobarbital treatment was also attended by a decrease in the intrahepatic content of [(3)H]vitamin D(3) (11.7+/-0.4 vs. 17.5+/-0.7 dpm/mg liver protein, P < 0.001) without alterations in the content of [(3)H]25-hydroxyvitamin D(3). The data collectively suggest that the increased hepatic conversion of [(3)H]vitamin D(3) to [(3)H]25-hydroxyvitamin D(3) attending phenobarbital treatment is secondary to stimulation of the hepatic 25-hydroxylation system(s) by a metabolite of phenobarbital other than p-hydroxyphenobarbital and/or by metabolic alterations resulting from phenobarbital therapy."}
{"id": "PMID:225353", "title": "Chemotactic factor inactivation by the myeloperoxidase-hydrogen peroxide-halide system.", "content": "Polymorphonuclear leukocytes may modulate the acute inflammatory response by the secretion of enzymes capable of inactivating mediators of inflammation. The ability of the myeloperoxidase-H(2)O(2)-halide system of the neutrophil to inactivate chemoattractants was examined using both a radioassay and a morphologic assay of chemotaxis. Incubation of either a complement-derived agent, C5a, or a synthetic formyl-methionyl peptide chemoattractant with the myeloperoxidase system for 15 min at 37 degrees C resulted in essentially complete loss of chemotactic activity. Inactivation was dependent on enzymatically active myeloperoxidase, H(2)O(2) or a peroxide-generating enzyme system, and a halide cofactor. It was blocked by agents which inhibit peroxidase (azide) or degrade H(2)O(2) (catalase). Inactivation of chemoattractants was time-dependent, reaching maximal levels within 1-5 min, and temperature-dependent with no significant inactivation occurring at 0 degrees C. H(2)O(2) alone had no significant inactivating ability at concentrations as high as 10 mM, whereas in the presence of myeloperoxidase and a halide, 0.1 muM H(2)O(2) showed significant activity and 10 muM H(2)O(2) caused complete inactivation. On a molar basis, the order of effectiveness of the halide cofactors was Br(-) > I(-) > Cl(-), although only chloride was fully active at physiologic concentrations. Neutrophils stimulated by phagocytosis or by membraneperturbing agents secrete enzymatic constituents, including myeloperoxidase, and metabolic products such as H(2)O(2). Thus, it is suggested that the myeloperoxidase system acting at an extracellular site serves as an inflammatory control mechanism by virtue of its ability to inactivate neutrophil chemoattractants.", "contents": "Chemotactic factor inactivation by the myeloperoxidase-hydrogen peroxide-halide system. Polymorphonuclear leukocytes may modulate the acute inflammatory response by the secretion of enzymes capable of inactivating mediators of inflammation. The ability of the myeloperoxidase-H(2)O(2)-halide system of the neutrophil to inactivate chemoattractants was examined using both a radioassay and a morphologic assay of chemotaxis. Incubation of either a complement-derived agent, C5a, or a synthetic formyl-methionyl peptide chemoattractant with the myeloperoxidase system for 15 min at 37 degrees C resulted in essentially complete loss of chemotactic activity. Inactivation was dependent on enzymatically active myeloperoxidase, H(2)O(2) or a peroxide-generating enzyme system, and a halide cofactor. It was blocked by agents which inhibit peroxidase (azide) or degrade H(2)O(2) (catalase). Inactivation of chemoattractants was time-dependent, reaching maximal levels within 1-5 min, and temperature-dependent with no significant inactivation occurring at 0 degrees C. H(2)O(2) alone had no significant inactivating ability at concentrations as high as 10 mM, whereas in the presence of myeloperoxidase and a halide, 0.1 muM H(2)O(2) showed significant activity and 10 muM H(2)O(2) caused complete inactivation. On a molar basis, the order of effectiveness of the halide cofactors was Br(-) > I(-) > Cl(-), although only chloride was fully active at physiologic concentrations. Neutrophils stimulated by phagocytosis or by membraneperturbing agents secrete enzymatic constituents, including myeloperoxidase, and metabolic products such as H(2)O(2). Thus, it is suggested that the myeloperoxidase system acting at an extracellular site serves as an inflammatory control mechanism by virtue of its ability to inactivate neutrophil chemoattractants."}
{"id": "PMID:225354", "title": "Metabolic fate of chylomicron phospholipids and apoproteins in the rat.", "content": "To study the metabolic fate of chylomicron phospholipid and apoproteins, 15 mg of doubly labeled ([(3)H]leu, [(32)P]phospholipid) rat mesenteric lymph chylomicrons were injected as an intravenous bolus into conscious rats. The specific radioactivity, composition, pool size, and morphology of the plasma lipoproteins were determined after 2-60 min. After injection of chylomicrons, there was a rapid transfer of radioactivity into high density lipoproteins (HDL). At peak specific activity in HDL (2-5 min), 35% of injected apoprotein and 25% of phospholipid radioactivity were recovered in HDL (d 1.063-1.21 g/ml), with smaller recoveries in other lipoproteins and liver. There was an initial rapid rise of (32)P specific activity in HDL and d 1.02-1.063 lipoproteins (low density lipoproteins [LDL]), but whereas LDL specific activity subsequently converged with that of d < 1.02 lipoproteins, HDL specific activity decayed more rapidly than LDL or d < 1.02 lipoproteins. Lipolysis of chylomicrons was associated with a transfer of phospholipid mass into LDL and HDL. At 5 min, 80% of injected triglyceride had been lipolyzed and there was a significant increase in phospholipid mass in LDL and a smaller increase in HDL. At 10 min, the mass of phospholipid in LDL had returned towards control values, and there was a further increase in phospholipid mass in HDL, which suggested phospholipid transfer from LDL to HDL. In donor lymph chylomicrons (3)H-radioactivity was present in apoprotein (apo)B, apoA-I, and apoA-IV, but only radioactivity of apoA-I and apoA-IV were transferred to HDL. Transfer of radioactivity was associated with loss of mass of apoA-I and apoA-IV from the fraction that contained the chylomicron remnants (d < 1.02). With injection of 15 mg chylomicron, there was a small but insignificant increase in the relatively large pool of HDL apoA-I. However, 60 min after injection of 250 mg of human or rat intestinal chylomicrons into the rat, there was a significant increase in HDL apoA-I that resulted from acquisition of a major fraction of the chylomicron apoA-I. After injection of chylomicrons, phospholipid vesicles were observed by negative stain electron microscopy in the LDL and HDL ultracentrifugal fractions, especially in the LDL. Upon addition of an osmotically active compound, cellobiose, vesicles were observed as flattened particles with a double lipid bilayer thickness ( congruent with 100 A). To validate further the identity of these particles, chylomicrons were injected into rats with [(3)H]glucose, and the recipient rats' plasma was fractionated by chromatography on 6% agarose. Trapping of [(3)H]glucose occurred in the void and LDL regions of the column, and vesicular particles were identified in these column fractions by negative stain electron microscopy. Catabolism of chylomicrons is associated with a rapid transfer of phospholipid, apoA-I, and possibly apoA-IV into HDL. Chylomicron phospholipid appears to give rise to vesicles which are probably incorporated into preexisting HDL. Chylomicron surface components may be an important source of plasma HDL.", "contents": "Metabolic fate of chylomicron phospholipids and apoproteins in the rat. To study the metabolic fate of chylomicron phospholipid and apoproteins, 15 mg of doubly labeled ([(3)H]leu, [(32)P]phospholipid) rat mesenteric lymph chylomicrons were injected as an intravenous bolus into conscious rats. The specific radioactivity, composition, pool size, and morphology of the plasma lipoproteins were determined after 2-60 min. After injection of chylomicrons, there was a rapid transfer of radioactivity into high density lipoproteins (HDL). At peak specific activity in HDL (2-5 min), 35% of injected apoprotein and 25% of phospholipid radioactivity were recovered in HDL (d 1.063-1.21 g/ml), with smaller recoveries in other lipoproteins and liver. There was an initial rapid rise of (32)P specific activity in HDL and d 1.02-1.063 lipoproteins (low density lipoproteins [LDL]), but whereas LDL specific activity subsequently converged with that of d < 1.02 lipoproteins, HDL specific activity decayed more rapidly than LDL or d < 1.02 lipoproteins. Lipolysis of chylomicrons was associated with a transfer of phospholipid mass into LDL and HDL. At 5 min, 80% of injected triglyceride had been lipolyzed and there was a significant increase in phospholipid mass in LDL and a smaller increase in HDL. At 10 min, the mass of phospholipid in LDL had returned towards control values, and there was a further increase in phospholipid mass in HDL, which suggested phospholipid transfer from LDL to HDL. In donor lymph chylomicrons (3)H-radioactivity was present in apoprotein (apo)B, apoA-I, and apoA-IV, but only radioactivity of apoA-I and apoA-IV were transferred to HDL. Transfer of radioactivity was associated with loss of mass of apoA-I and apoA-IV from the fraction that contained the chylomicron remnants (d < 1.02). With injection of 15 mg chylomicron, there was a small but insignificant increase in the relatively large pool of HDL apoA-I. However, 60 min after injection of 250 mg of human or rat intestinal chylomicrons into the rat, there was a significant increase in HDL apoA-I that resulted from acquisition of a major fraction of the chylomicron apoA-I. After injection of chylomicrons, phospholipid vesicles were observed by negative stain electron microscopy in the LDL and HDL ultracentrifugal fractions, especially in the LDL. Upon addition of an osmotically active compound, cellobiose, vesicles were observed as flattened particles with a double lipid bilayer thickness ( congruent with 100 A). To validate further the identity of these particles, chylomicrons were injected into rats with [(3)H]glucose, and the recipient rats' plasma was fractionated by chromatography on 6% agarose. Trapping of [(3)H]glucose occurred in the void and LDL regions of the column, and vesicular particles were identified in these column fractions by negative stain electron microscopy. Catabolism of chylomicrons is associated with a rapid transfer of phospholipid, apoA-I, and possibly apoA-IV into HDL. Chylomicron phospholipid appears to give rise to vesicles which are probably incorporated into preexisting HDL. Chylomicron surface components may be an important source of plasma HDL."}
{"id": "PMID:225355", "title": "Maternal stress and pituitary-adrenal manipulations during pregnancy in rats: effects on morphology and sexual behavior of male offspring.", "content": "The purpose of the present study was to determine whether the demasculinizing and feminizing effects of prenatal stress (i.e., stress applied to the mother during pregnancy) in rats reported previously are mediated by activation of the maternal pituitary-adrenal axis. Neither whole-body restraint, with or without hyperthermia, nor ACTH treatment during the last third of gestation had any reliable effect on masculine or feminine sexual behavior in male Sprague-Dawley offspring, although these treatments produced maternal pathology and evidence of maternal adrenocorticoid release. Significant littermate similarity was found for almost every morphological and behavioral measure. Failure to control for the litter variable may account for many previously reported effects of prenatal stress on sexual behavior in rats. The discrepancy between the present and earlier findings is discussed in terms of methodological and theoretical considerations.", "contents": "Maternal stress and pituitary-adrenal manipulations during pregnancy in rats: effects on morphology and sexual behavior of male offspring. The purpose of the present study was to determine whether the demasculinizing and feminizing effects of prenatal stress (i.e., stress applied to the mother during pregnancy) in rats reported previously are mediated by activation of the maternal pituitary-adrenal axis. Neither whole-body restraint, with or without hyperthermia, nor ACTH treatment during the last third of gestation had any reliable effect on masculine or feminine sexual behavior in male Sprague-Dawley offspring, although these treatments produced maternal pathology and evidence of maternal adrenocorticoid release. Significant littermate similarity was found for almost every morphological and behavioral measure. Failure to control for the litter variable may account for many previously reported effects of prenatal stress on sexual behavior in rats. The discrepancy between the present and earlier findings is discussed in terms of methodological and theoretical considerations."}
{"id": "PMID:225356", "title": "Regulation of cyclic AMP metabolism and lipolysis in isolated rat fat cells by insulin, N6-(phenylisopropyl) adenosine and 2',5'-dideoxyadenosine.", "content": "The increases in cyclic AMP accumulation and lipolysis by rat fat cells incubated in the presence of catecholamines were abolished by N6-(phenylisopropyl) adenosine. The same inhibition of cyclic AMP accumulation was seen in the presence of 2',5'-dideoxyadenosine but lipolysis was unaffected. In contrast, insulin inhibited lipolysis without affecting cyclic AMP accumulation by norepinephrine plus adenosine deaminase. These results suggest that there are either multiple pools of cyclic AMP or that ther exists some other mechanism which is involved in the regulation of lipolysis by hormones.", "contents": "Regulation of cyclic AMP metabolism and lipolysis in isolated rat fat cells by insulin, N6-(phenylisopropyl) adenosine and 2',5'-dideoxyadenosine. The increases in cyclic AMP accumulation and lipolysis by rat fat cells incubated in the presence of catecholamines were abolished by N6-(phenylisopropyl) adenosine. The same inhibition of cyclic AMP accumulation was seen in the presence of 2',5'-dideoxyadenosine but lipolysis was unaffected. In contrast, insulin inhibited lipolysis without affecting cyclic AMP accumulation by norepinephrine plus adenosine deaminase. These results suggest that there are either multiple pools of cyclic AMP or that ther exists some other mechanism which is involved in the regulation of lipolysis by hormones."}
{"id": "PMID:225357", "title": "Comparison of cyclic nucleotide binding to adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate-dependent protein kinases.", "content": "Binding sites for [3H]cAMP on purified regulatory dimers of type II A-kinase (II-R2) are independent as assessed by equilibrium binding (KD = 6 +/- 1.3 nM at pH 7.2, 25 degrees; nH = 1.0) and by the lack of effect of unlabeled cAMP on dissociation rate (kd = 1.0 X 10(-3) sec -1 at pH 7.2, 25 degrees). In contrast, binding sites for [3H]cGMP on purified G-kinase displayed positively cooperative interactions in both equilibrium and dissociation assays with convex upward Scatchard plots, an nH of 1.6 and a dissociation rate (kd = 6.2 X 10(-3) sec-1 at pH 6.8, 0 degree) which was slowed by excess unlabeled cGMP (kd = 1.13 X 10(-3) sec-1 at pH 6.8, degree). Calculated transition state free energies of dissociation revealed that dissociation of nucleotide from G-kinase in the presence of cGMP was restrained by an energy barrier (20.8 kcal.mol-1) similar to that of II-R2 (20.9 kcal.mol-1), whereas dissociation from G-kinase without excess nucleotide occurred more easily (18.9 kcal.mol-1).", "contents": "Comparison of cyclic nucleotide binding to adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate-dependent protein kinases. Binding sites for [3H]cAMP on purified regulatory dimers of type II A-kinase (II-R2) are independent as assessed by equilibrium binding (KD = 6 +/- 1.3 nM at pH 7.2, 25 degrees; nH = 1.0) and by the lack of effect of unlabeled cAMP on dissociation rate (kd = 1.0 X 10(-3) sec -1 at pH 7.2, 25 degrees). In contrast, binding sites for [3H]cGMP on purified G-kinase displayed positively cooperative interactions in both equilibrium and dissociation assays with convex upward Scatchard plots, an nH of 1.6 and a dissociation rate (kd = 6.2 X 10(-3) sec-1 at pH 6.8, 0 degree) which was slowed by excess unlabeled cGMP (kd = 1.13 X 10(-3) sec-1 at pH 6.8, degree). Calculated transition state free energies of dissociation revealed that dissociation of nucleotide from G-kinase in the presence of cGMP was restrained by an energy barrier (20.8 kcal.mol-1) similar to that of II-R2 (20.9 kcal.mol-1), whereas dissociation from G-kinase without excess nucleotide occurred more easily (18.9 kcal.mol-1)."}
{"id": "PMID:225358", "title": "Correlation between cyclic AMP levels and calcium efflux in isolated renal cortical tubules.", "content": "Isolated renal cortical tubules from male hamsters were utilized to examine the possible relationship between cyclic AMP (cAMP) and efflux of calcium. Both parathyroid hormone (PTH) and prostaglandin E1 (PGE1) produced dose-related increases in cAMP levels and calcium efflux from isolated tubules. Maximal concentrations of both hormones resulted in changes in cAMP which were 6 fold greater and changes in calcium efflux which were 2 fold greater with PGE1 than with PTH. Effects of sub-maximal amounts of either hormone on both cAMP and calcium efflux were potentiated to tubule incubations resulted in increases in tissue-associated cAMP over the same degree by inclusion of methyl-isobutylxanthine (MIX). Addition of either exogenous cAMP or dibutyryl cAMP (db-cAMP) produced dose-related increases in calcium efflux which occurred more rapidly with db-cAMP than with cAMP. Increasing amounts of cAMP added to the same concentration range resulting in increases in calcium efflux. Addition of 2', 3' cyclic AMP, 5'AMP or db-cyclic GMP had no significant effect on calcium efflux while 3', 5' cyclic CMP significantly reduced this response. The results indicate that cAMP increases efflux of calcium from renal tubules and may play a central role in hormone-dependent transport of this ion.", "contents": "Correlation between cyclic AMP levels and calcium efflux in isolated renal cortical tubules. Isolated renal cortical tubules from male hamsters were utilized to examine the possible relationship between cyclic AMP (cAMP) and efflux of calcium. Both parathyroid hormone (PTH) and prostaglandin E1 (PGE1) produced dose-related increases in cAMP levels and calcium efflux from isolated tubules. Maximal concentrations of both hormones resulted in changes in cAMP which were 6 fold greater and changes in calcium efflux which were 2 fold greater with PGE1 than with PTH. Effects of sub-maximal amounts of either hormone on both cAMP and calcium efflux were potentiated to tubule incubations resulted in increases in tissue-associated cAMP over the same degree by inclusion of methyl-isobutylxanthine (MIX). Addition of either exogenous cAMP or dibutyryl cAMP (db-cAMP) produced dose-related increases in calcium efflux which occurred more rapidly with db-cAMP than with cAMP. Increasing amounts of cAMP added to the same concentration range resulting in increases in calcium efflux. Addition of 2', 3' cyclic AMP, 5'AMP or db-cyclic GMP had no significant effect on calcium efflux while 3', 5' cyclic CMP significantly reduced this response. The results indicate that cAMP increases efflux of calcium from renal tubules and may play a central role in hormone-dependent transport of this ion."}
{"id": "PMID:225375", "title": "Studies on the specificity of immunohistochemical techniques for cyclic AMP and cyclic GMP.", "content": "Immunohistochemical studies employing antibodies against cyclic nucleotides indicate that cyclic AMP and cyclic GMP are localized to distinct subcellular sites. These antibodies, however, cross-react weakly with noncyclic nucleotides (eg. ATP, GTP), and therefore we investigated the speficity of the immunohistochemical technique. Slides of fetal nuclei exposed to gaseous nitrous acid demonstrated reduced immunofluorescence. The slides were then incubated with cyclic and noncyclic nucleotides, and restoration of distinct cyclic AMP and cyclic GMP staining pattern was achieved only with appropriate cyclic nucleotides. Antibodies that were used have a greater affinity for acetylated derivatives of cyclic nucleotides. By using a gas phase technique, tissue slices were acetylated and immunohistochemical staining intensity was compared with the effect of acetylation on antibody affinity for various nucleotides. Acetylation greatly increased affinity of cyclic AMP antibody for cyclic AMP but not other nucleotides, and greatly intensified cyclic AMP staining. Acetylation moderately increased affinity of cyclic GMP antibody for cyclic GMP, and moderately intensified cyclic GMP staining. Both nitrous acid and acetylation studies support the specificity of the immunohistochemical method for cyclic nucleotides.", "contents": "Studies on the specificity of immunohistochemical techniques for cyclic AMP and cyclic GMP. Immunohistochemical studies employing antibodies against cyclic nucleotides indicate that cyclic AMP and cyclic GMP are localized to distinct subcellular sites. These antibodies, however, cross-react weakly with noncyclic nucleotides (eg. ATP, GTP), and therefore we investigated the speficity of the immunohistochemical technique. Slides of fetal nuclei exposed to gaseous nitrous acid demonstrated reduced immunofluorescence. The slides were then incubated with cyclic and noncyclic nucleotides, and restoration of distinct cyclic AMP and cyclic GMP staining pattern was achieved only with appropriate cyclic nucleotides. Antibodies that were used have a greater affinity for acetylated derivatives of cyclic nucleotides. By using a gas phase technique, tissue slices were acetylated and immunohistochemical staining intensity was compared with the effect of acetylation on antibody affinity for various nucleotides. Acetylation greatly increased affinity of cyclic AMP antibody for cyclic AMP but not other nucleotides, and greatly intensified cyclic AMP staining. Acetylation moderately increased affinity of cyclic GMP antibody for cyclic GMP, and moderately intensified cyclic GMP staining. Both nitrous acid and acetylation studies support the specificity of the immunohistochemical method for cyclic nucleotides."}
{"id": "PMID:225377", "title": "Potential inhibitors of rat tooth alkaline phosphatase studied by means of different histochemical techniques.", "content": "Two histochemical methods for demonstration of alkaline phosphatase activity, a lead pyrophosphate- anda naphtholphosphate technique, were compared. Since different results may be due to methodological differences as well as different enzyme activities, the enzymatic hydrolysis of the naphtholphosphate was visualized both by means of an azo-dye coupler and by lead-capturing of the liberated phosphate ion. Various potential inhibitors of alkaline phosphatase activity (diphosphonate, D-penicillamine, and sodium fluoride) were also tested. The use of diphosphonate and D-penicillamine resulted in inhibited or reduced staining, which could mainly be explained by an interference by these compounds with components in the incubation media rather than with the enzyme itself. The addition of sodium fluoride had no effect on the naphtholphosphate staining pattern irrespective of capturing method, whereas the odontoblastic pyrophosphate splitting alkaline phosphatase appeared to be sensitive to sodium fluoride, suggesting the presence of two alkaline phosphatases in odontoblasts.", "contents": "Potential inhibitors of rat tooth alkaline phosphatase studied by means of different histochemical techniques. Two histochemical methods for demonstration of alkaline phosphatase activity, a lead pyrophosphate- anda naphtholphosphate technique, were compared. Since different results may be due to methodological differences as well as different enzyme activities, the enzymatic hydrolysis of the naphtholphosphate was visualized both by means of an azo-dye coupler and by lead-capturing of the liberated phosphate ion. Various potential inhibitors of alkaline phosphatase activity (diphosphonate, D-penicillamine, and sodium fluoride) were also tested. The use of diphosphonate and D-penicillamine resulted in inhibited or reduced staining, which could mainly be explained by an interference by these compounds with components in the incubation media rather than with the enzyme itself. The addition of sodium fluoride had no effect on the naphtholphosphate staining pattern irrespective of capturing method, whereas the odontoblastic pyrophosphate splitting alkaline phosphatase appeared to be sensitive to sodium fluoride, suggesting the presence of two alkaline phosphatases in odontoblasts."}
{"id": "PMID:225360", "title": "Sleep apnea syndrome: report of case.", "content": "Sleep apnea syndrome encompasses several entities that are characterized by the inability of the victim to achieve restful sleep. The only known treatment for the syndrome is a tracheostomy. Further research and experimentation are required. We are of the opinion that the appliance described in this article offers some promise as an alternative treatment.", "contents": "Sleep apnea syndrome: report of case. Sleep apnea syndrome encompasses several entities that are characterized by the inability of the victim to achieve restful sleep. The only known treatment for the syndrome is a tracheostomy. Further research and experimentation are required. We are of the opinion that the appliance described in this article offers some promise as an alternative treatment."}
{"id": "PMID:225379", "title": "The demonstration of antibody specificity by a new technique. The gel electrophoresis-derived enzyme-linked immunosorbent assay (GEDELISA) and its application to antibodies specific for feline leukemia virus.", "content": "By combining the high resolution of sodium dodecylsulfate polyacrylamide gel electrophoresis with the sensitivity of enzyme-linked immunosorbent assay (ELISA) antibodies specific for different feline leukemia virus components are characterized. Based on the same principle, Concanavalin A binding sites of FeLV components are also detected.", "contents": "The demonstration of antibody specificity by a new technique. The gel electrophoresis-derived enzyme-linked immunosorbent assay (GEDELISA) and its application to antibodies specific for feline leukemia virus. By combining the high resolution of sodium dodecylsulfate polyacrylamide gel electrophoresis with the sensitivity of enzyme-linked immunosorbent assay (ELISA) antibodies specific for different feline leukemia virus components are characterized. Based on the same principle, Concanavalin A binding sites of FeLV components are also detected."}
{"id": "PMID:225380", "title": "Ultrastructural demonstration of cytochrome oxidase via cytochrome C in cerebral cortex.", "content": "A procedure for the ultrastructural cytochemical localization of cytochrome oxidase via cytochrome c in the cerebral cortex is described. Vascular perfusion fixation by formaldehyde and glutaraldehyde of different concentrations and mixtures of the two gave varying results. A mixture of 4% formaldehyde and 0.5% glutaraldehyde gave the best combination of ultrastructural preservation and retention of enzyme activity. Histochemical methods were examined for optimum incubation conditions, based on the oxidative polymerization of 3,3'-diaminobenzidine (DAB) to an osmiophilic product. The reaction product was discretely localized within intercristate and the intermembrane space of mitochondria. The staining pattern was the same in nerve cells and in neuroglia and their processed. The DAB reaction product was also found in mitochondria of the endothelial cells.", "contents": "Ultrastructural demonstration of cytochrome oxidase via cytochrome C in cerebral cortex. A procedure for the ultrastructural cytochemical localization of cytochrome oxidase via cytochrome c in the cerebral cortex is described. Vascular perfusion fixation by formaldehyde and glutaraldehyde of different concentrations and mixtures of the two gave varying results. A mixture of 4% formaldehyde and 0.5% glutaraldehyde gave the best combination of ultrastructural preservation and retention of enzyme activity. Histochemical methods were examined for optimum incubation conditions, based on the oxidative polymerization of 3,3'-diaminobenzidine (DAB) to an osmiophilic product. The reaction product was discretely localized within intercristate and the intermembrane space of mitochondria. The staining pattern was the same in nerve cells and in neuroglia and their processed. The DAB reaction product was also found in mitochondria of the endothelial cells."}
{"id": "PMID:225381", "title": "Morphogenesis of cerebral matrix ectopies in human fetus and newborn.", "content": "The subject of investigations was genesis of periventricular, cerebral matrix ectopies in human fetuses and newborns. The morphologic and histochemical analysis concerned the embryonal elements of the ventricular wall: namely neuroepithelium with membrana limitans externa and suporficial layer of the germinal matrix. It has been distinguished four stages in the development of ectopic changes: 1) atrophy of neuroepithelium, 2) superficial necrobiosis with disruption of membrana limitans externa, 3) egsophytic neuroglial ectopies with organization or sequestration within the ventricular light, 4) neuroeptithelial inclusions in the periventricular zone. The disclosed, destructive changes in superficial layers of the germinal matrix as well as their glial organization suggested that reparative processes that could be an evidence of the passed perinatal hypoxia occur in the ventricular light.", "contents": "Morphogenesis of cerebral matrix ectopies in human fetus and newborn. The subject of investigations was genesis of periventricular, cerebral matrix ectopies in human fetuses and newborns. The morphologic and histochemical analysis concerned the embryonal elements of the ventricular wall: namely neuroepithelium with membrana limitans externa and suporficial layer of the germinal matrix. It has been distinguished four stages in the development of ectopic changes: 1) atrophy of neuroepithelium, 2) superficial necrobiosis with disruption of membrana limitans externa, 3) egsophytic neuroglial ectopies with organization or sequestration within the ventricular light, 4) neuroeptithelial inclusions in the periventricular zone. The disclosed, destructive changes in superficial layers of the germinal matrix as well as their glial organization suggested that reparative processes that could be an evidence of the passed perinatal hypoxia occur in the ventricular light."}
{"id": "PMID:225382", "title": "Synaptic organization of the medial acessory olivary nucleus of the cat.", "content": "Light microscopically the morphological characteristic of neurons and ultrastructurally the synaptic organization of medial accessory olivary nucleus of cat was studied. Different types of chemically mediated as well as electric synapses were observed. The terminal boutons contain mainly clear synaptic vesicles, but small and large dense core vesicles are also available. In the neuropil of the nucleus characteristic glomeruli with central dendritic core were establish. The dendritic profiles were connected with numerous gap junctions and attachment plaques. The apposition without any synaptic specializations in a large area of the cell membrane of adjacent neurons was also observed. In some cases oval structures with size 450--650 A which we called submembraneous dense bodies were established under one of the apposite membranes.", "contents": "Synaptic organization of the medial acessory olivary nucleus of the cat. Light microscopically the morphological characteristic of neurons and ultrastructurally the synaptic organization of medial accessory olivary nucleus of cat was studied. Different types of chemically mediated as well as electric synapses were observed. The terminal boutons contain mainly clear synaptic vesicles, but small and large dense core vesicles are also available. In the neuropil of the nucleus characteristic glomeruli with central dendritic core were establish. The dendritic profiles were connected with numerous gap junctions and attachment plaques. The apposition without any synaptic specializations in a large area of the cell membrane of adjacent neurons was also observed. In some cases oval structures with size 450--650 A which we called submembraneous dense bodies were established under one of the apposite membranes."}
{"id": "PMID:225383", "title": "A prospective study of corticosteroid and catecholamine levels in relation to viral respiratory illness.", "content": "Urinary 17-OHCS, epinephrine and norepinephrine levels were studied for one week before and one week after the onset of acute, severe Adenovirus 4 respiratory illness in 12 Army recruits during Basic Combat Training. During the pre-illness period, a tendency was frequently noted for all three hormone levels to show \"spiking\" elevations two to four days before illness onset. There was also a tendency for 17-OHCS levels to rise on the day before fever onset. The possible relationship of these pre-illness hormonal changes to stressful experiences and, in turn, to altered host resistance to infectious illness is discussed. Following onset of respiratory illness, 17-OHCS, epinephrine and norepinephrine levels all showed about 60 percent increases over the early pre-illness period baseline value. Elevations of these hormones persisted for about four to five days, roughly in correlation with fever duration, with only slight differences in configuration and timing of curves from one hormone to the next. The problem of evaluating which of several independent variables operating concurrently during infectious illness may be responsible for stimulating the final common neuroendocrine pathways is discussed.", "contents": "A prospective study of corticosteroid and catecholamine levels in relation to viral respiratory illness. Urinary 17-OHCS, epinephrine and norepinephrine levels were studied for one week before and one week after the onset of acute, severe Adenovirus 4 respiratory illness in 12 Army recruits during Basic Combat Training. During the pre-illness period, a tendency was frequently noted for all three hormone levels to show \"spiking\" elevations two to four days before illness onset. There was also a tendency for 17-OHCS levels to rise on the day before fever onset. The possible relationship of these pre-illness hormonal changes to stressful experiences and, in turn, to altered host resistance to infectious illness is discussed. Following onset of respiratory illness, 17-OHCS, epinephrine and norepinephrine levels all showed about 60 percent increases over the early pre-illness period baseline value. Elevations of these hormones persisted for about four to five days, roughly in correlation with fever duration, with only slight differences in configuration and timing of curves from one hormone to the next. The problem of evaluating which of several independent variables operating concurrently during infectious illness may be responsible for stimulating the final common neuroendocrine pathways is discussed."}
{"id": "PMID:225385", "title": "Early events in thymocyte activation. II. Changes in nonhistone chromatin proteins induced by a thymus-dependent human serum factor.", "content": "Previously, it has been shown that a human thymus-dependent serum factor (SF), isolated from peripheral blood and acting on precursors of mature T lymphocytes, induces an increase in the synthesis of cyclic AMP and proteins in thymocytes. We have now investigated the action of SF on the incorporation of 3H-leucine and 32P-orthophosphate into nuclear proteins of thymocytes after 15 to 240 min of culture. SF induced a rapid increase in the synthesis and phosphorylation of nuclear proteins, especially in the phosphorylated nonhistone chromatin proteins (P-NHCP). Electrophoretic patterns in polyacrylamide gels of the P-NHCP fractions, extracted from the chromatin of the stimulated cells, showed that proteins with m.w. higher than 50 x 10(3) were synthesized to a larger extent as compared with unstimulated cells. These data suggest that SF acts specifically on the synthesis of P-NHCP and may in this way control DNA-template activity.", "contents": "Early events in thymocyte activation. II. Changes in nonhistone chromatin proteins induced by a thymus-dependent human serum factor. Previously, it has been shown that a human thymus-dependent serum factor (SF), isolated from peripheral blood and acting on precursors of mature T lymphocytes, induces an increase in the synthesis of cyclic AMP and proteins in thymocytes. We have now investigated the action of SF on the incorporation of 3H-leucine and 32P-orthophosphate into nuclear proteins of thymocytes after 15 to 240 min of culture. SF induced a rapid increase in the synthesis and phosphorylation of nuclear proteins, especially in the phosphorylated nonhistone chromatin proteins (P-NHCP). Electrophoretic patterns in polyacrylamide gels of the P-NHCP fractions, extracted from the chromatin of the stimulated cells, showed that proteins with m.w. higher than 50 x 10(3) were synthesized to a larger extent as compared with unstimulated cells. These data suggest that SF acts specifically on the synthesis of P-NHCP and may in this way control DNA-template activity."}
{"id": "PMID:225386", "title": "Separation of functional subpopulations of murine and human lymphoid cells on colloidal silica density gradients. I. Preparation of the Ludox AM gradient material and characterization of separation capacities.", "content": "This report describes a unique modification of an isopycnic density gradient system utilizing as a separating menstrum colloidal silica (Ludox AM). The primary advantages of this preparation are: (1) It is chemically defined, allowing extremely reproducible cell separation employing different lots of material; (2) the physical parameters (pH, density, salt concentration) of the final gradient suspension can be manipulated over a wide range of values, allowing for the separation of many different biological materials; (3) it allows separation of very large numbers of lymphoid cells with greater than 95% recovery of applied cells; (4) separated cellular subpopulations can be easily washed free of silica and cellular function is retained. This paper is a report of the preparation and functional characteristics of the gradient material as it relates to the separation of very large numbers of lymphoid cell subpopulations in both mouse and man. Subpopulations of murine and human lymphocytes separated by this gradient material were assayed for IgM synthesis, T-cell mediated cytotoxicity, and lymphokine production.", "contents": "Separation of functional subpopulations of murine and human lymphoid cells on colloidal silica density gradients. I. Preparation of the Ludox AM gradient material and characterization of separation capacities. This report describes a unique modification of an isopycnic density gradient system utilizing as a separating menstrum colloidal silica (Ludox AM). The primary advantages of this preparation are: (1) It is chemically defined, allowing extremely reproducible cell separation employing different lots of material; (2) the physical parameters (pH, density, salt concentration) of the final gradient suspension can be manipulated over a wide range of values, allowing for the separation of many different biological materials; (3) it allows separation of very large numbers of lymphoid cells with greater than 95% recovery of applied cells; (4) separated cellular subpopulations can be easily washed free of silica and cellular function is retained. This paper is a report of the preparation and functional characteristics of the gradient material as it relates to the separation of very large numbers of lymphoid cell subpopulations in both mouse and man. Subpopulations of murine and human lymphocytes separated by this gradient material were assayed for IgM synthesis, T-cell mediated cytotoxicity, and lymphokine production."}
{"id": "PMID:225389", "title": "Surface analysis by bacterial adherence to virus-infected cells.", "content": "A rapid and inexpensive assay has been developed for the examination of new antigens on the surface of whole eucaryotic cells. This assay is based on the specific tagging of antigen-antibody complexes at the cell surface with Staphylococcus aureus. Cells that had been infected with vesicular stomatitis virus were exposed to specific antiserum, were then exposed to the bacteria, and finally were examined in the light microscope. Almost 100% of infected cells reacted positively. Two temperature-sensitive mutants of vesicular stomatitis virus were employed to determine which virus-specific antigen interacted with antibody and resulted in adherence of bacteria to the cells. Examination of cells infected with either ts G41 or ts 045 at the nonpermissive temperature showed that the assay by bacterial adherence measured the presence of only the viral glycoprotein at the cell surface. Internal viral antigens or readsorbed extracellular virions did not result in bacterial adherence. This assay has potential widespread significance for diagnostic medicine as well as for rapid and sensitive analyses of cell surfaces.", "contents": "Surface analysis by bacterial adherence to virus-infected cells. A rapid and inexpensive assay has been developed for the examination of new antigens on the surface of whole eucaryotic cells. This assay is based on the specific tagging of antigen-antibody complexes at the cell surface with Staphylococcus aureus. Cells that had been infected with vesicular stomatitis virus were exposed to specific antiserum, were then exposed to the bacteria, and finally were examined in the light microscope. Almost 100% of infected cells reacted positively. Two temperature-sensitive mutants of vesicular stomatitis virus were employed to determine which virus-specific antigen interacted with antibody and resulted in adherence of bacteria to the cells. Examination of cells infected with either ts G41 or ts 045 at the nonpermissive temperature showed that the assay by bacterial adherence measured the presence of only the viral glycoprotein at the cell surface. Internal viral antigens or readsorbed extracellular virions did not result in bacterial adherence. This assay has potential widespread significance for diagnostic medicine as well as for rapid and sensitive analyses of cell surfaces."}
{"id": "PMID:225390", "title": "A solid-phase radioimmunoassay for detection of IgM antibodies to hepatitis A virus.", "content": "The conditions for a sensitive and specific solid-phase radioimmunoassay (RIA) for the detection of IgM antibodies to hepatitis A virus (HAV) were optimized, and the RIA was used to assay sera from patients with hepatitis. IgM antibodies to HAV reached highest concentrations between one and three weeks after onset of icterus and were measurable in follow-up sera for at least 12 months after infection. To prove the specificity, the IgG antibodies were separated from patient sera by sucrose density-gradient centrifugation. The remaining IgM antibodies, after treatment with beta-mercaptoethanol, did not bind in the RIA, and, when the anti-IgM antibody bound to the solid phase was replaced with anti-IgG, a negative result was obtained with incubation of IgM antibody to HAV. Also, the presence of IgG was shown not to interfere with measurement of IgM antibody to HAV. Finally, as a further specificity control, 50 sera positive for rheumatoid factor or from patients infected with hepatitis B virus, cytomegalic inclusion disease, infectious mononucleosis, influenza A virus, rubella, or measles were tested, and all of these sera were negative for IgM antibody to HAV.", "contents": "A solid-phase radioimmunoassay for detection of IgM antibodies to hepatitis A virus. The conditions for a sensitive and specific solid-phase radioimmunoassay (RIA) for the detection of IgM antibodies to hepatitis A virus (HAV) were optimized, and the RIA was used to assay sera from patients with hepatitis. IgM antibodies to HAV reached highest concentrations between one and three weeks after onset of icterus and were measurable in follow-up sera for at least 12 months after infection. To prove the specificity, the IgG antibodies were separated from patient sera by sucrose density-gradient centrifugation. The remaining IgM antibodies, after treatment with beta-mercaptoethanol, did not bind in the RIA, and, when the anti-IgM antibody bound to the solid phase was replaced with anti-IgG, a negative result was obtained with incubation of IgM antibody to HAV. Also, the presence of IgG was shown not to interfere with measurement of IgM antibody to HAV. Finally, as a further specificity control, 50 sera positive for rheumatoid factor or from patients infected with hepatitis B virus, cytomegalic inclusion disease, infectious mononucleosis, influenza A virus, rubella, or measles were tested, and all of these sera were negative for IgM antibody to HAV."}
{"id": "PMID:225392", "title": "Selective polymyositis inducted by coxsackievirus B1 in mice.", "content": "A high-passage laboratory strain of coxsackievirus B1 produced a unique myositis that predominantly and profoundly affected hip extensors and, to a lesser extent, hindquarter knee flexors when inoculated into a strain of random-bred newborn mice of Swiss origin (COH mice). The effect was not observed in BALB/c or C3H mice similarly inoculated. In addition to the differences in susceptibility of the mouse strains, it was found that six different low-passage \"field\" isolates of coxsackie-virus B1 isolated from infected patients varied considerably in their capability to induce these lesions. Thus, selective myositis which is muscle group-specific can be induced in a mouse model with coxsackievirus B1, and both genetic factors of the host and characteristics of the virus strain play a significant role in the pathogenesis of the myositis.", "contents": "Selective polymyositis inducted by coxsackievirus B1 in mice. A high-passage laboratory strain of coxsackievirus B1 produced a unique myositis that predominantly and profoundly affected hip extensors and, to a lesser extent, hindquarter knee flexors when inoculated into a strain of random-bred newborn mice of Swiss origin (COH mice). The effect was not observed in BALB/c or C3H mice similarly inoculated. In addition to the differences in susceptibility of the mouse strains, it was found that six different low-passage \"field\" isolates of coxsackie-virus B1 isolated from infected patients varied considerably in their capability to induce these lesions. Thus, selective myositis which is muscle group-specific can be induced in a mouse model with coxsackievirus B1, and both genetic factors of the host and characteristics of the virus strain play a significant role in the pathogenesis of the myositis."}
{"id": "PMID:225399", "title": "Inhibition of the development of spontaneous hypertension in SH rats by gonadectomy or estradiol.", "content": "Young male and female rats that become spontaneously hypertensive when they mature were gonadectomized at 30 days of age while they were still normotensive. Gonadectomy retarded the usual steep ascent of blood pressure up to 120 days of age. Ovariectomized females \"escaped\" from this inhibiting effect, and blood pressure rose to severely high levels, i.e., 210 mm Hg, from 150 to 240 days. Treatment with testosterone or estradiol demonstrated that estradiol was particularly effective in inhibiting the usual rise in blood pressure in intact (sham-operated) or gonadectomized males and females. Although effectively lowering blood pressure, estradiol also caused increased pituitary and adrenal weights, hyperlipidemia, and increased circulating levels of corticosterone and DOC.", "contents": "Inhibition of the development of spontaneous hypertension in SH rats by gonadectomy or estradiol. Young male and female rats that become spontaneously hypertensive when they mature were gonadectomized at 30 days of age while they were still normotensive. Gonadectomy retarded the usual steep ascent of blood pressure up to 120 days of age. Ovariectomized females \"escaped\" from this inhibiting effect, and blood pressure rose to severely high levels, i.e., 210 mm Hg, from 150 to 240 days. Treatment with testosterone or estradiol demonstrated that estradiol was particularly effective in inhibiting the usual rise in blood pressure in intact (sham-operated) or gonadectomized males and females. Although effectively lowering blood pressure, estradiol also caused increased pituitary and adrenal weights, hyperlipidemia, and increased circulating levels of corticosterone and DOC."}
{"id": "PMID:225400", "title": "Chemodectomas: review and report of nine cases.", "content": "We have reviewed the broad spectrum of disease caused by chemodectomas. This spectrum extends from the benign to the aggressively malignant with many graduations in-between. Our analyses included cases from the literature and nine new cases seen over the past twenty-five years. Surgery as the primary and most definitive form of therapy, is recommended if feasible, with total excision as the goal, in both benign and malignant histologies. An excellent outcome is to be expected in benign cases. At present, no predictor exists to foretell the behavior of malignant lesions, which can range from the aggressive to the slowly progressive. Both radiotherapy and chemotherapy have been tried in malignant cases. No consistent good result has occurred from the use of either. The future will hopefully bring us more effective therapy.", "contents": "Chemodectomas: review and report of nine cases. We have reviewed the broad spectrum of disease caused by chemodectomas. This spectrum extends from the benign to the aggressively malignant with many graduations in-between. Our analyses included cases from the literature and nine new cases seen over the past twenty-five years. Surgery as the primary and most definitive form of therapy, is recommended if feasible, with total excision as the goal, in both benign and malignant histologies. An excellent outcome is to be expected in benign cases. At present, no predictor exists to foretell the behavior of malignant lesions, which can range from the aggressive to the slowly progressive. Both radiotherapy and chemotherapy have been tried in malignant cases. No consistent good result has occurred from the use of either. The future will hopefully bring us more effective therapy."}
{"id": "PMID:225402", "title": "Adrenocortical function and a field population of a macropodid marsupial (Setonix brachyurus, Quoy and Gaimard).", "content": "Concentrations of corticosteroids and aldosterone have been measured in the plasma and related to the maximum cortisol binding capacity, to the concentration of sodium and potassium of the plasma and to the condition of the animals, in a natural population of the quokka (Setonix brachyurus, Quoy & Gaimard) on Rottnest Island, Western Australia. A marked population in one area has been repetitively sampled at approximately 6 week intervals over a period of 2 years. Animals were found to be in significantly better condition during the hot-dry season. Their plasma concentrations of corticosteroids, 1.09 +/- 0.11 (S.E.M.) and 1.47 +/- 0.14 microgram/100 ml and their plasma sodium concentrations, 147 +/- 0.87 and 142 +/- 1.17 mequiv/1, for the hot-dry and cold-wet seasons respectively, were both significantly different (P less than 0.05). Plasma concentrations of aldosterone were 8.40 +/- 0.57 and 7.06 +/- 0.53 ng/100 ml for the hot-dry and cold-wet seasons. The level of aldosterone fell to levels comparable to those found in salt-replete laboratory animals only during the month of July. In the laboratory, salt deprivation resulted in a significant rise in the concentration of plasma aldosterone, 2.33 +/- 0.57 (S.E.M.) ng/100 ml when salt-replete and 16.95 +/- 2.74 ng/100 ml when salt-deprived (P less than 0.001). Total plasma corticosteroid levels were unaffected by changes in the sodium content of the diet. Injections of ACTH at a rate of 2 i.u./kg caused a significant rise in the levels of plasma corticosteroids which were essentially identical in both high- and low-condition animals. Both temperature fell to a significantly lower level in low-condition animals held in cages after injection of ACTH. These results indicate that the seasonal mortality of th quokka on Rottnest Island does not result from any breakdown in adrenal function, despite a substantial decline in the condition of the animals.", "contents": "Adrenocortical function and a field population of a macropodid marsupial (Setonix brachyurus, Quoy and Gaimard). Concentrations of corticosteroids and aldosterone have been measured in the plasma and related to the maximum cortisol binding capacity, to the concentration of sodium and potassium of the plasma and to the condition of the animals, in a natural population of the quokka (Setonix brachyurus, Quoy & Gaimard) on Rottnest Island, Western Australia. A marked population in one area has been repetitively sampled at approximately 6 week intervals over a period of 2 years. Animals were found to be in significantly better condition during the hot-dry season. Their plasma concentrations of corticosteroids, 1.09 +/- 0.11 (S.E.M.) and 1.47 +/- 0.14 microgram/100 ml and their plasma sodium concentrations, 147 +/- 0.87 and 142 +/- 1.17 mequiv/1, for the hot-dry and cold-wet seasons respectively, were both significantly different (P less than 0.05). Plasma concentrations of aldosterone were 8.40 +/- 0.57 and 7.06 +/- 0.53 ng/100 ml for the hot-dry and cold-wet seasons. The level of aldosterone fell to levels comparable to those found in salt-replete laboratory animals only during the month of July. In the laboratory, salt deprivation resulted in a significant rise in the concentration of plasma aldosterone, 2.33 +/- 0.57 (S.E.M.) ng/100 ml when salt-replete and 16.95 +/- 2.74 ng/100 ml when salt-deprived (P less than 0.001). Total plasma corticosteroid levels were unaffected by changes in the sodium content of the diet. Injections of ACTH at a rate of 2 i.u./kg caused a significant rise in the levels of plasma corticosteroids which were essentially identical in both high- and low-condition animals. Both temperature fell to a significantly lower level in low-condition animals held in cages after injection of ACTH. These results indicate that the seasonal mortality of th quokka on Rottnest Island does not result from any breakdown in adrenal function, despite a substantial decline in the condition of the animals."}
{"id": "PMID:225403", "title": "Distribution and degradation of two tritium-labelled corticotrophin analogues in the rat.", "content": "The distribution and degradation of corticotrophin-(1--24)-tetracosapeptide specifically labelled with tritium at Tyr2, Phe7 or Tyr23 and [D-Ser1, Lys17, Lys18]-corticotrophin-(1--18)-octadecapeptide amide labelled at Tyr2 were studied at various times after intravenous injection into rats. By characterizing the radioactivity in plasma and various tissues, an overall picture of the metabolic handling of the two peptides emerged. The peptides left the circulation rapidly, entering mainly muscle and skin where they were extensively degraded. The D-Ser1-containing analogue was less rapidly degraded and intact peptide persisted in muscle and skin for up to 1 h. This peptide probably returned to the circulation giving rise to the sustained plasma levels observed after injection of the D-Ser1-substituted octadecapeptide but not after injection of the tetracosapeptide. Although initially the kidneys did not clear such large amounts of peptide as did muscle and skin they played an important role by continuously and, on the basis of existing evidence, irreversibly clearing the peptides and peptide fragments from the circulation and degrading them.", "contents": "Distribution and degradation of two tritium-labelled corticotrophin analogues in the rat. The distribution and degradation of corticotrophin-(1--24)-tetracosapeptide specifically labelled with tritium at Tyr2, Phe7 or Tyr23 and [D-Ser1, Lys17, Lys18]-corticotrophin-(1--18)-octadecapeptide amide labelled at Tyr2 were studied at various times after intravenous injection into rats. By characterizing the radioactivity in plasma and various tissues, an overall picture of the metabolic handling of the two peptides emerged. The peptides left the circulation rapidly, entering mainly muscle and skin where they were extensively degraded. The D-Ser1-containing analogue was less rapidly degraded and intact peptide persisted in muscle and skin for up to 1 h. This peptide probably returned to the circulation giving rise to the sustained plasma levels observed after injection of the D-Ser1-substituted octadecapeptide but not after injection of the tetracosapeptide. Although initially the kidneys did not clear such large amounts of peptide as did muscle and skin they played an important role by continuously and, on the basis of existing evidence, irreversibly clearing the peptides and peptide fragments from the circulation and degrading them."}
{"id": "PMID:225406", "title": "Synaptic facilitation in Aplysia explored by random presynaptic stimulation.", "content": "The identified interneuron L10 in the abdominal ganglion of Aplysia was stimulated to fire action potentials in a random sequence while the early inhibitory potential of its follower cell L2 was recorded. Application of Wiener nonlinear analysis to these data yielded a predictive model of the facilitating postsynaptic potential. The model shows that facilitation changes both the time-course and the magnitude of the early synaptic potential. The facilitated response has a longer duration than the unfacilitated response. Its magnitude is exponentially decreasing with increasing interstimulus interval between test and conditioning stimuli. Facilitation is abolished at short interstimulus intervals. The hypothesis that the magnitude only of transmitter release is increased cannot explain these results. The observed facilitation may be due to characteristics of pre- and postsynaptic morphology.", "contents": "Synaptic facilitation in Aplysia explored by random presynaptic stimulation. The identified interneuron L10 in the abdominal ganglion of Aplysia was stimulated to fire action potentials in a random sequence while the early inhibitory potential of its follower cell L2 was recorded. Application of Wiener nonlinear analysis to these data yielded a predictive model of the facilitating postsynaptic potential. The model shows that facilitation changes both the time-course and the magnitude of the early synaptic potential. The facilitated response has a longer duration than the unfacilitated response. Its magnitude is exponentially decreasing with increasing interstimulus interval between test and conditioning stimuli. Facilitation is abolished at short interstimulus intervals. The hypothesis that the magnitude only of transmitter release is increased cannot explain these results. The observed facilitation may be due to characteristics of pre- and postsynaptic morphology."}
{"id": "PMID:225407", "title": "Light-initiated changes of cyclic guanosine monophosphate levels in the frog retina measured with quick-freezing techniques.", "content": "Although there is good agreement that light reduces the amount of cyclic GMP (cGMP) in the retina, the exact time-course of this decrease is not well established. Bullfrog retinal sections were isolated under infrared light and quick-frozen with liquid nitrogen-cooled, metal hammers after exposure to various intensities of continuous illumination. This quick-freezing should stop the degradation of cGMP within 50-100 ms. The frozen retinal sections were then slowly warmed up in the presence of perchloric acid to denature enzymes involved in cGmp metabolism. cGMP was determined by radioimmunoassay and comparison was made between light- and dark-adapted retinal sections from the same animal. The average cGMP concentration was 44.3 +/- 0.7 pmol cGMP/mg protein or 170.9 +/- 3.2 pmol cGMP/retina. After 1 s of illumination no significant change in cGMP concentration was found even with the brightest light used (approximately 7 x 10(7) rhodopsins bleached/second per rod. At this intensity the first significant decrease in cGMP from dark-adapted levels was detected 3-5 s after the initiation of illumination; cGMP decayed to 70-75% of the dark-adapted value after approximately 30 s. With lower intensity illumination the cGMP levels recovered to dark-adapted levels after the initial decrease even though the bleaching light remained on.", "contents": "Light-initiated changes of cyclic guanosine monophosphate levels in the frog retina measured with quick-freezing techniques. Although there is good agreement that light reduces the amount of cyclic GMP (cGMP) in the retina, the exact time-course of this decrease is not well established. Bullfrog retinal sections were isolated under infrared light and quick-frozen with liquid nitrogen-cooled, metal hammers after exposure to various intensities of continuous illumination. This quick-freezing should stop the degradation of cGMP within 50-100 ms. The frozen retinal sections were then slowly warmed up in the presence of perchloric acid to denature enzymes involved in cGmp metabolism. cGMP was determined by radioimmunoassay and comparison was made between light- and dark-adapted retinal sections from the same animal. The average cGMP concentration was 44.3 +/- 0.7 pmol cGMP/mg protein or 170.9 +/- 3.2 pmol cGMP/retina. After 1 s of illumination no significant change in cGMP concentration was found even with the brightest light used (approximately 7 x 10(7) rhodopsins bleached/second per rod. At this intensity the first significant decrease in cGMP from dark-adapted levels was detected 3-5 s after the initiation of illumination; cGMP decayed to 70-75% of the dark-adapted value after approximately 30 s. With lower intensity illumination the cGMP levels recovered to dark-adapted levels after the initial decrease even though the bleaching light remained on."}
{"id": "PMID:225408", "title": "The preparation and chemical composition of fractions from Aspergillus fumigatus wall and protoplasts possessing antigenic activity.", "content": "A detergent-soluble fraction was prepared from the fragmented wall of Aspergillus fumigatus mycelium using the non-ionic detergent Triton X-100, and a wall-free extract was prepared from the same source in the form of protoplasts, released by a lytic enzyme system from Trichoderma harzianum. These extracts were examined by polyacrylamide gel electrophoresis and their detailed chemical composition was established. They were compared with the water-soluble fraction prepared from total mycelium, which is used routinely in this laboratory for serological tests. All fractions had immunological reactivity towards an antiserum prepared in rabbits against this water-soluble fraction of the mycelium, as shown by double diffusion. Both protein and carbohydrate moieties appear to be involved in the antigenic sites, with carbohydrate reactivity predominantly associated with the protoplast fraction. The fact that all preparations contained at least one common antigenic determinant, as judged by lines of identity to a single antiserum, is discussed in relation to antigen location.", "contents": "The preparation and chemical composition of fractions from Aspergillus fumigatus wall and protoplasts possessing antigenic activity. A detergent-soluble fraction was prepared from the fragmented wall of Aspergillus fumigatus mycelium using the non-ionic detergent Triton X-100, and a wall-free extract was prepared from the same source in the form of protoplasts, released by a lytic enzyme system from Trichoderma harzianum. These extracts were examined by polyacrylamide gel electrophoresis and their detailed chemical composition was established. They were compared with the water-soluble fraction prepared from total mycelium, which is used routinely in this laboratory for serological tests. All fractions had immunological reactivity towards an antiserum prepared in rabbits against this water-soluble fraction of the mycelium, as shown by double diffusion. Both protein and carbohydrate moieties appear to be involved in the antigenic sites, with carbohydrate reactivity predominantly associated with the protoplast fraction. The fact that all preparations contained at least one common antigenic determinant, as judged by lines of identity to a single antiserum, is discussed in relation to antigen location."}
{"id": "PMID:225409", "title": "The role of manganese in growth and sporulation of Bacillus subtilis.", "content": "Phosphoglycerate phosphomutase of Bacillus subtilis, Bacillus cereus and Bacillus megaterium required Mn2+ as cofactor, whereas the wheat germ and rabbit liver enzymes did not. In the absence of Mn2+, B. subtilis did not sporulate in normal sporulation media but it did sporulate if the proper ratio of glucose or glycerol and malate was used. Decoyinine, an inhibitor of guanosine monophosphate synthesis, induced sporulation in the presence of excess glucose and malate to the same extent with and without Mn2+. Apparently, phosphoglycerate phosphomutase is the only strictly Mn2+-requiring enzyme needed for optimal sporulation in normal sporulation media.", "contents": "The role of manganese in growth and sporulation of Bacillus subtilis. Phosphoglycerate phosphomutase of Bacillus subtilis, Bacillus cereus and Bacillus megaterium required Mn2+ as cofactor, whereas the wheat germ and rabbit liver enzymes did not. In the absence of Mn2+, B. subtilis did not sporulate in normal sporulation media but it did sporulate if the proper ratio of glucose or glycerol and malate was used. Decoyinine, an inhibitor of guanosine monophosphate synthesis, induced sporulation in the presence of excess glucose and malate to the same extent with and without Mn2+. Apparently, phosphoglycerate phosphomutase is the only strictly Mn2+-requiring enzyme needed for optimal sporulation in normal sporulation media."}
{"id": "PMID:225410", "title": "Selective advantage of a Spirillum sp. in a carbon-limited environment. Accumulation of poly-beta-hydroxybutyric acid and its role in starvation.", "content": "A freshwater Spirillum sp., which apparently belongs to a niche of low nutritional status (Matin & Veldkamp, 1978), accumulated poly-beta-hydroxybutyric acid (PHB) during lactate-limited growth in continuous culture. The PHB content varied in a complex manner with the dilution rate (D), but was greatest at the lowest D value examined: about 18% (w/w) at D = 0.025 h-1. It is not known what mechanism accounted for PHB accumulation during carbon-limited growth. The resistance of cultures of Spirillum sp. to starvation after growth at various D values was compared with that of a Pseudomonas sp. which appears to belong to relatively richer environments (Matin & Veldkamp, 1978) and does not accumulate PHB. In Spirillum sp., resistance correlated directly with the PHB content of the culture subjected to starvation, whereas in Pseudomonas sp. it increased with RNA content. Further, after growth at D = 0.03 to 0.05 h-1, the Spirillum sp. was much more resistant to starvation than was the Pseudomonas sp. Since the microflora of oligotrophic environments are probably often subjected to starvation conditions, PHB accumulation by Spirillum sp. during growth in such environments may assist survival. PHB in Spirillum sp. was rapidly degraded during starvation but it had no sparing effect on RNA degradation. It is not known how PHB enhanced resistance to starvation.", "contents": "Selective advantage of a Spirillum sp. in a carbon-limited environment. Accumulation of poly-beta-hydroxybutyric acid and its role in starvation. A freshwater Spirillum sp., which apparently belongs to a niche of low nutritional status (Matin & Veldkamp, 1978), accumulated poly-beta-hydroxybutyric acid (PHB) during lactate-limited growth in continuous culture. The PHB content varied in a complex manner with the dilution rate (D), but was greatest at the lowest D value examined: about 18% (w/w) at D = 0.025 h-1. It is not known what mechanism accounted for PHB accumulation during carbon-limited growth. The resistance of cultures of Spirillum sp. to starvation after growth at various D values was compared with that of a Pseudomonas sp. which appears to belong to relatively richer environments (Matin & Veldkamp, 1978) and does not accumulate PHB. In Spirillum sp., resistance correlated directly with the PHB content of the culture subjected to starvation, whereas in Pseudomonas sp. it increased with RNA content. Further, after growth at D = 0.03 to 0.05 h-1, the Spirillum sp. was much more resistant to starvation than was the Pseudomonas sp. Since the microflora of oligotrophic environments are probably often subjected to starvation conditions, PHB accumulation by Spirillum sp. during growth in such environments may assist survival. PHB in Spirillum sp. was rapidly degraded during starvation but it had no sparing effect on RNA degradation. It is not known how PHB enhanced resistance to starvation."}
{"id": "PMID:225411", "title": "Interferon susceptibility of various cell lines persistently infected with haemagglutinating virus of Japan (HVJ).", "content": "Various cell lines persistently infected with para-influenza 1 virus, HVJ strain, were less susceptible to the antiviral action of interferon than the same cell lines when not infected with HVJ. When Vero cells persistently infected with a temperature-sensitive strain of HVJ were incubated at 38 degrees C, a non-permissive temperature, they became fully susceptible to interferon, whereas neither the haemadsorbing nor the cell-associated haemagglutinating activity of the virus was expressed. These findings suggest that the lowered interferon susceptibility of virus-carrier cells may be related to the maturation of virus in them. It was found that the low susceptibility of virus-carrier cells to interferon is not due to blocked adsorption of interferon or to inability of the cells to respond tointerferon. Studies with actinomycin D suggest that some step (or steps) before the synthesis of the messenger RNA for the antiviral protein is blocked.", "contents": "Interferon susceptibility of various cell lines persistently infected with haemagglutinating virus of Japan (HVJ). Various cell lines persistently infected with para-influenza 1 virus, HVJ strain, were less susceptible to the antiviral action of interferon than the same cell lines when not infected with HVJ. When Vero cells persistently infected with a temperature-sensitive strain of HVJ were incubated at 38 degrees C, a non-permissive temperature, they became fully susceptible to interferon, whereas neither the haemadsorbing nor the cell-associated haemagglutinating activity of the virus was expressed. These findings suggest that the lowered interferon susceptibility of virus-carrier cells may be related to the maturation of virus in them. It was found that the low susceptibility of virus-carrier cells to interferon is not due to blocked adsorption of interferon or to inability of the cells to respond tointerferon. Studies with actinomycin D suggest that some step (or steps) before the synthesis of the messenger RNA for the antiviral protein is blocked."}
{"id": "PMID:225412", "title": "Suppressive effects of interferon on syncytium formation by RD-114 virus in human transformed cells.", "content": "The RD-114 virus rapidly induced syncytia in the human transformed cell lines, RSa, RSb and IFr. Treatment of the virus with heat or ultrasonic vibration completely eliminated the syncytium-forming activity. Irradiation with u.v.-light or treatment with beta-propiolactone (BPL) reduced but did not completely destroy the activity. Pre-treatment of the cells for 16 h with 25 to 500 units/ml of human leucocyte interferon (Le-IF) or fibroblast interferon (F-IF) significantly reduced formation of syncytia by active virus or inactivated (u.v. or BPL) virus. This activity of interferon was inhibited by treatment of the cells with cycloheximide. Interferon did not increase the binding of 3H-uridine-labelled RD-114 virus to the cells. It is postulated that interferon treatment altered the plasma membrane of the cells and thus reduced their capacity to fuse.", "contents": "Suppressive effects of interferon on syncytium formation by RD-114 virus in human transformed cells. The RD-114 virus rapidly induced syncytia in the human transformed cell lines, RSa, RSb and IFr. Treatment of the virus with heat or ultrasonic vibration completely eliminated the syncytium-forming activity. Irradiation with u.v.-light or treatment with beta-propiolactone (BPL) reduced but did not completely destroy the activity. Pre-treatment of the cells for 16 h with 25 to 500 units/ml of human leucocyte interferon (Le-IF) or fibroblast interferon (F-IF) significantly reduced formation of syncytia by active virus or inactivated (u.v. or BPL) virus. This activity of interferon was inhibited by treatment of the cells with cycloheximide. Interferon did not increase the binding of 3H-uridine-labelled RD-114 virus to the cells. It is postulated that interferon treatment altered the plasma membrane of the cells and thus reduced their capacity to fuse."}
{"id": "PMID:225413", "title": "Membrane glycoproteins and antigens induced by human cytomegalovirus.", "content": "Early after infection of cells with cytomegalovirus, the membranes were modified with respect to both glycoprotein composition and immunological specificity. Virus-specified antigens were inserted into the plasma membrane at 24 h after infection, as much as 2 days before virion and dense body maturation. Although at least four virus-induced glycoproteins were synthesized and bound to plasma and microsomal membranes between 20 and 24 h after infection, virus-specified antigen accumulated primarily on the plasma membrane. In contrast, at late times (72 h) after infection when virus nucleocapsids can be detected in the necleus, virus-specified antigen was prominent on the plasma, endoplasmic reticulum and nuclear membranes. It is proposed that the virus-specified glycoproteins and antigens of this herpesvirus accumulate first on the plasma membrane and then on internal membranes. The appearance of virus-specified antigen on internal membranes coincides with the commencement of virion and dense body envelopment.", "contents": "Membrane glycoproteins and antigens induced by human cytomegalovirus. Early after infection of cells with cytomegalovirus, the membranes were modified with respect to both glycoprotein composition and immunological specificity. Virus-specified antigens were inserted into the plasma membrane at 24 h after infection, as much as 2 days before virion and dense body maturation. Although at least four virus-induced glycoproteins were synthesized and bound to plasma and microsomal membranes between 20 and 24 h after infection, virus-specified antigen accumulated primarily on the plasma membrane. In contrast, at late times (72 h) after infection when virus nucleocapsids can be detected in the necleus, virus-specified antigen was prominent on the plasma, endoplasmic reticulum and nuclear membranes. It is proposed that the virus-specified glycoproteins and antigens of this herpesvirus accumulate first on the plasma membrane and then on internal membranes. The appearance of virus-specified antigen on internal membranes coincides with the commencement of virion and dense body envelopment."}
{"id": "PMID:225414", "title": "Cell-free varicella-zoster virus in cultured human melanoma cells.", "content": "Varicella-zoster virus (VZV) has been isolated and serially propagated in a continuous cell line derived from a human malignant melanoma tumour. Human melanoma cells (HMC) have been further evaluated as a substrate for the production of cell-free virus and compare favourably with human embryo cells. Within 60 h after inoculation with VZV-infected cells, HMC monolayers incubated at 32 degrees C exhibited advanced syncytial cytopathic effect, and the overlying culture medium contained greater than 10(2) p.f.u./ml. The cell pellet from a mechanically dispersed 150 cm2 monolayer yielded 10(5) p.f.u. after sonic disruption, while the medium ('scraping medium') in which the cells had been harvested contained up to one log more infectious virus than was found in the cells from the same monolayer. When infected cells were subjected to Dounce homogenization, most of the infectivity was found in the nuclear fraction. The concentration and purification of cell-free virus were also investigated. Concentration was carried out by three methods: ultracentrifugation, dialysis against hydrophilic compounds and liquid polymer phase separation. The first two procedures caused considerable loss of biological activity, whereas precipitation with 8% polyethylene glycol resulted in a 50-fold increase in titre. Purification of cell-free virus with retention of infectivity was achieved by rate zonal centrifugation in linear potassium tartrate gradients. Infectious virus was also recovered after sedimentation in combination equilibrium-viscosity gradients of potassium tartrate and glycerol, but not after centrifugation to equilibrium in caesium chloride gradients.", "contents": "Cell-free varicella-zoster virus in cultured human melanoma cells. Varicella-zoster virus (VZV) has been isolated and serially propagated in a continuous cell line derived from a human malignant melanoma tumour. Human melanoma cells (HMC) have been further evaluated as a substrate for the production of cell-free virus and compare favourably with human embryo cells. Within 60 h after inoculation with VZV-infected cells, HMC monolayers incubated at 32 degrees C exhibited advanced syncytial cytopathic effect, and the overlying culture medium contained greater than 10(2) p.f.u./ml. The cell pellet from a mechanically dispersed 150 cm2 monolayer yielded 10(5) p.f.u. after sonic disruption, while the medium ('scraping medium') in which the cells had been harvested contained up to one log more infectious virus than was found in the cells from the same monolayer. When infected cells were subjected to Dounce homogenization, most of the infectivity was found in the nuclear fraction. The concentration and purification of cell-free virus were also investigated. Concentration was carried out by three methods: ultracentrifugation, dialysis against hydrophilic compounds and liquid polymer phase separation. The first two procedures caused considerable loss of biological activity, whereas precipitation with 8% polyethylene glycol resulted in a 50-fold increase in titre. Purification of cell-free virus with retention of infectivity was achieved by rate zonal centrifugation in linear potassium tartrate gradients. Infectious virus was also recovered after sedimentation in combination equilibrium-viscosity gradients of potassium tartrate and glycerol, but not after centrifugation to equilibrium in caesium chloride gradients."}
{"id": "PMID:225415", "title": "The polypeptide and the DNA restriction enzyme profiles of spontaneous isolates of herpes simplex virus type 1 from explants of human trigeminal, superior cervical and vagus ganglia.", "content": "Analysis of the infected cell polypeptides and the DNA restriction profiles of 31 HSV-1 isolates from the trigeminal, superior cervical and vagus ganglia from 17 individuals (12 U.S.A., 2 Japanese, 3 Norwegian) could be classified as 15 different virus strains. With the exception of the three Norwegian isolates which gave identical profiles, virus isolates from the ganglia of different individuals could all be distinguished from one another. In contrast virus isolates from the trigeminal, superior cervical and vagus ganglia of the same individual, or virus isolates from the left and right ganglia of the same individual or multiple isolates from different explants of a single ganglion were indistinguishable. In conclusion, a single virus strain infects each individual initially and virus descended from this event subsequently infects and becomes latent in different cells of the same ganglion as well as in different ganglia.", "contents": "The polypeptide and the DNA restriction enzyme profiles of spontaneous isolates of herpes simplex virus type 1 from explants of human trigeminal, superior cervical and vagus ganglia. Analysis of the infected cell polypeptides and the DNA restriction profiles of 31 HSV-1 isolates from the trigeminal, superior cervical and vagus ganglia from 17 individuals (12 U.S.A., 2 Japanese, 3 Norwegian) could be classified as 15 different virus strains. With the exception of the three Norwegian isolates which gave identical profiles, virus isolates from the ganglia of different individuals could all be distinguished from one another. In contrast virus isolates from the trigeminal, superior cervical and vagus ganglia of the same individual, or virus isolates from the left and right ganglia of the same individual or multiple isolates from different explants of a single ganglion were indistinguishable. In conclusion, a single virus strain infects each individual initially and virus descended from this event subsequently infects and becomes latent in different cells of the same ganglion as well as in different ganglia."}
{"id": "PMID:225416", "title": "An interferon-sensitive early step in the establishment of infection of murine cells by murine sarcoma/leukaemia virus.", "content": "NIH 3T3 mouse cells were infected at very high multiplicity with murine sarcoma/leukaemia virus (MSV/MLV) and then cloned. All of the 48 clones obtained were morphologically transformed, all but one showed anchorage-independence of growth, typical of MSV-transformed NIH 3T3 cells and most (91%) produced MSV/MLV. When cells which had been pre-treated with 10(4) units/ml of purified interferon (IF) were infected under the same conditions and then cloned in the presence of the same amount of IF, only 6 of a total of 63 clones were morphologically transformed. All but these 6 showed a degree of anchorage-independence typical of the uninfected parental cells and very few (2.4%) produced virus. Furthermore, the MSV genome could not be rescued in any of the 23 clones tested and only 1 out of 10 clones produced tumours. The properties of these clones remained stable over a period of 10 to 20 passages in the absence of interferon. We conclude that interferon can irreversibly block an early step in the MSV/MLV infectious process.", "contents": "An interferon-sensitive early step in the establishment of infection of murine cells by murine sarcoma/leukaemia virus. NIH 3T3 mouse cells were infected at very high multiplicity with murine sarcoma/leukaemia virus (MSV/MLV) and then cloned. All of the 48 clones obtained were morphologically transformed, all but one showed anchorage-independence of growth, typical of MSV-transformed NIH 3T3 cells and most (91%) produced MSV/MLV. When cells which had been pre-treated with 10(4) units/ml of purified interferon (IF) were infected under the same conditions and then cloned in the presence of the same amount of IF, only 6 of a total of 63 clones were morphologically transformed. All but these 6 showed a degree of anchorage-independence typical of the uninfected parental cells and very few (2.4%) produced virus. Furthermore, the MSV genome could not be rescued in any of the 23 clones tested and only 1 out of 10 clones produced tumours. The properties of these clones remained stable over a period of 10 to 20 passages in the absence of interferon. We conclude that interferon can irreversibly block an early step in the MSV/MLV infectious process."}
{"id": "PMID:225417", "title": "Plaque formation by a host range mutant of vaccinia virus in non-permissive cells co-infected with Yaba virus.", "content": "A host-dependent conditional lethal mutant of vaccinia virus strain DIs was rescued to form plaques in a non-permissive cell line JINET co-infected with Yaba virus, a poxvirus serologically distant from the rescued virus. The efficiency of plaque formation under optimal conditions in this system was comparable to that in Vero cells which were permissive for the mutant. The plaque number of the mutant in JINET cells was influenced greatly by the multiplicity of Yaba virus, the interval between inoculations with DIs and Yaba virus and the maintenance medium for pre-infection of cells with Yaba virus. The plaque formation by DIs in JINET cells was suppressed or inhibited when the duration of pre-infection with high multiplicities of Yaba virus was prolonged. Thus, Yaba virus possessed both rescuing and inhibitory activities on DIs and the plaque number of DIs in doubly infected cells was thought to be determined by the balance between the two activities. Ultraviolet light-inactivated Yaba virus retained rescuing activity on DIs in JINET cells.", "contents": "Plaque formation by a host range mutant of vaccinia virus in non-permissive cells co-infected with Yaba virus. A host-dependent conditional lethal mutant of vaccinia virus strain DIs was rescued to form plaques in a non-permissive cell line JINET co-infected with Yaba virus, a poxvirus serologically distant from the rescued virus. The efficiency of plaque formation under optimal conditions in this system was comparable to that in Vero cells which were permissive for the mutant. The plaque number of the mutant in JINET cells was influenced greatly by the multiplicity of Yaba virus, the interval between inoculations with DIs and Yaba virus and the maintenance medium for pre-infection of cells with Yaba virus. The plaque formation by DIs in JINET cells was suppressed or inhibited when the duration of pre-infection with high multiplicities of Yaba virus was prolonged. Thus, Yaba virus possessed both rescuing and inhibitory activities on DIs and the plaque number of DIs in doubly infected cells was thought to be determined by the balance between the two activities. Ultraviolet light-inactivated Yaba virus retained rescuing activity on DIs in JINET cells."}
{"id": "PMID:225418", "title": "High C + G content in parapoxvirus DNA.", "content": "The DNAs of eight parapoxviruses (four stomatitis papulosa viruses isolated from infected calves, a pseudocowpox virus isolated from a teat lesion of an infected cow and three orf viruses, one isolated from an infected sheep and two isolated from human infections) were analysed in CsCl gradients. The mole % of G+C was calculated from the buoyant density and found to be approx. 63% for all virus isolates examined. Parapoxvirus DNA thus has by far the highest G+C content of all poxvirus DNAs so far examined.", "contents": "High C + G content in parapoxvirus DNA. The DNAs of eight parapoxviruses (four stomatitis papulosa viruses isolated from infected calves, a pseudocowpox virus isolated from a teat lesion of an infected cow and three orf viruses, one isolated from an infected sheep and two isolated from human infections) were analysed in CsCl gradients. The mole % of G+C was calculated from the buoyant density and found to be approx. 63% for all virus isolates examined. Parapoxvirus DNA thus has by far the highest G+C content of all poxvirus DNAs so far examined."}
{"id": "PMID:225419", "title": "Effect of mitomycin C and 60Co gamma-irradiation on the replication of SV40 in cell lines of varying permissivity for SV40 replication.", "content": "The effects of mitomycin C and 60Co gamma-irradiation, which induce production of SV40 from SV40-transformed hamster cells, on the replication of superinfecting SV40 or virus DNA in cells varying in permissivity for SV40 replication have been examined. These agents enhance replication of SV40 in an uninducible line of SV40-transformed hamster kidney cells and in nonpermissive secondary hamster kidney cells. The same treatments do not affect SV40 replication in semipermissive hamster (BHK21) and human (HEL, HEK) cells and inhibit SV40 replication in permissive monkey (TC-7) cells. We conclude that forms of induction treatment, such as mitomycin C or 60Co gamma-irradiation, modify the expression of host cell factors which determine the level of permissivity for SV40 infection.", "contents": "Effect of mitomycin C and 60Co gamma-irradiation on the replication of SV40 in cell lines of varying permissivity for SV40 replication. The effects of mitomycin C and 60Co gamma-irradiation, which induce production of SV40 from SV40-transformed hamster cells, on the replication of superinfecting SV40 or virus DNA in cells varying in permissivity for SV40 replication have been examined. These agents enhance replication of SV40 in an uninducible line of SV40-transformed hamster kidney cells and in nonpermissive secondary hamster kidney cells. The same treatments do not affect SV40 replication in semipermissive hamster (BHK21) and human (HEL, HEK) cells and inhibit SV40 replication in permissive monkey (TC-7) cells. We conclude that forms of induction treatment, such as mitomycin C or 60Co gamma-irradiation, modify the expression of host cell factors which determine the level of permissivity for SV40 infection."}
{"id": "PMID:225420", "title": "Tumour production by HSV-2 transformed lines in rats and the varying response to immunosuppression.", "content": "Rat embryo cells transformed by two ts mutants of HSV-2 strain HG 52 and also by u.v.-irradiated HSV-2 strain 333 were inoculated into highly inbred host rats, either newborn or which had undergone various immunosuppressive treatments. The latent period before a palpable tumour (a fibrosarcoma) was detected varied directly with the degree of immunosuppression of the host. Transformed cells could form tumours after a latent period of nearly 2 years. All tumours were invasive and in some cases metastatic. The continuing expression of HSV information in 10 tumour cell lines was demonstrated by perinuclear and cytoplasmic staining in immunofluorescence studies using a rat antiserum directed against the early polypeptides of HSV-2 HG 52 infection and a rabbit serum prepared against a 24 h cell infection with HSV-2 HG 52 ts I. Sera from tumour-bearing rats fluoresced the surface of unfixed human or rat embryo cells 4 to 5 h after infection with HSV-2 HG 52. In addition the rabbit antiserum (4740 or 4741) fluoresced the surface of 80% of the tumour cells in culture. Transplanted tumours after 20 passages in vitro and taking up to a year to again form a tumour in a host rat also showed specific HSV cytoplasmic and perinuclear fluorescence in tests with the rat antiserum directed against early polypeptides of HSV-2 lytic infection.", "contents": "Tumour production by HSV-2 transformed lines in rats and the varying response to immunosuppression. Rat embryo cells transformed by two ts mutants of HSV-2 strain HG 52 and also by u.v.-irradiated HSV-2 strain 333 were inoculated into highly inbred host rats, either newborn or which had undergone various immunosuppressive treatments. The latent period before a palpable tumour (a fibrosarcoma) was detected varied directly with the degree of immunosuppression of the host. Transformed cells could form tumours after a latent period of nearly 2 years. All tumours were invasive and in some cases metastatic. The continuing expression of HSV information in 10 tumour cell lines was demonstrated by perinuclear and cytoplasmic staining in immunofluorescence studies using a rat antiserum directed against the early polypeptides of HSV-2 HG 52 infection and a rabbit serum prepared against a 24 h cell infection with HSV-2 HG 52 ts I. Sera from tumour-bearing rats fluoresced the surface of unfixed human or rat embryo cells 4 to 5 h after infection with HSV-2 HG 52. In addition the rabbit antiserum (4740 or 4741) fluoresced the surface of 80% of the tumour cells in culture. Transplanted tumours after 20 passages in vitro and taking up to a year to again form a tumour in a host rat also showed specific HSV cytoplasmic and perinuclear fluorescence in tests with the rat antiserum directed against early polypeptides of HSV-2 lytic infection."}
{"id": "PMID:225421", "title": "Studies of the replication of a bovine enterovirus RNA.", "content": "Replicative intermediate (RI), replicative form (RF) and single-stranded (SS) RNA have been isolated from BHK cells infected with a bovine enterovirus by salt precipitation and gel filtration techniques. Kinetic experiments showed that at no time up to 16 h post-infection (p.i.) did the amount of RF exceed that of RI or SS RNA. Electrophoresis of RF on 1.5% polyacrylamide-agarose gels showed that at least three species of double-stranded RNA were present, one of which was associated with an accessible poly(A)-containing tract. All of the RF was denatured by 99% dimethylsulphoxide (DMSO), although reannealling occurred rapidly when samples were returned to aqueous conditions. No evidence for circular structures in the RF molecular population was found by use of caesium sulphate density gradients containing ethidium bromide. Treatment of RI with ribonuclease produced double-stranded RNA molecules, some of which were smaller in size than intact RF. Denaturation with DMSO and analysis on 99% DMSO sucrose gradients showed that the RI did not contain single strands of greater length than virion RNA. A portion of the RI bound to poly(U)-Sepharose 4B columns. The poly(A) tracts involved were present only in the nascent RNA strands with greatest sedimentation coefficients (30 to 35S). Bovine enterovirus induced SS RNA was heterogeneous with regard to both sedimentation through sucrose gradients and mobility on acrylamide gels compared to purified virion RNA. The reason for this difference has never been satisfactorily resolved. Sedimentation through 99% DMSO-sucrose gradients showed that the heterogeneity was due to aggregation rather than any variation in chain length or conformational differences. Our results support the single-stranded template model rather than a circular model for picornavirus RNA replication.", "contents": "Studies of the replication of a bovine enterovirus RNA. Replicative intermediate (RI), replicative form (RF) and single-stranded (SS) RNA have been isolated from BHK cells infected with a bovine enterovirus by salt precipitation and gel filtration techniques. Kinetic experiments showed that at no time up to 16 h post-infection (p.i.) did the amount of RF exceed that of RI or SS RNA. Electrophoresis of RF on 1.5% polyacrylamide-agarose gels showed that at least three species of double-stranded RNA were present, one of which was associated with an accessible poly(A)-containing tract. All of the RF was denatured by 99% dimethylsulphoxide (DMSO), although reannealling occurred rapidly when samples were returned to aqueous conditions. No evidence for circular structures in the RF molecular population was found by use of caesium sulphate density gradients containing ethidium bromide. Treatment of RI with ribonuclease produced double-stranded RNA molecules, some of which were smaller in size than intact RF. Denaturation with DMSO and analysis on 99% DMSO sucrose gradients showed that the RI did not contain single strands of greater length than virion RNA. A portion of the RI bound to poly(U)-Sepharose 4B columns. The poly(A) tracts involved were present only in the nascent RNA strands with greatest sedimentation coefficients (30 to 35S). Bovine enterovirus induced SS RNA was heterogeneous with regard to both sedimentation through sucrose gradients and mobility on acrylamide gels compared to purified virion RNA. The reason for this difference has never been satisfactorily resolved. Sedimentation through 99% DMSO-sucrose gradients showed that the heterogeneity was due to aggregation rather than any variation in chain length or conformational differences. Our results support the single-stranded template model rather than a circular model for picornavirus RNA replication."}
{"id": "PMID:225422", "title": "Phosphorylation of arabinofuranosylthymine in non-infected and herpesvirus (TK+ and TK-)-infected cells.", "content": "The phosphorylation of arabinofuranosylthymine (araThd) has been studied both in non-infected cells and in those infected with herpes simplex virus (HSV-1, Lennette; HSV-1, IES and HSV-2, D-316). In these experiments, HSV strains were used which either contain (Lennette, TK+ and D-316 TK+) or lack (IES, TK-) the capacity to induce pyrimidine deoxyribonucleoside kinase. It was found that extracellularly administered araThd is phosphorylated to ara TTP via araTMP and araTDP in both non-infected and in HSV-infected cells. The phosphorylating capacity is more than tenfold lower in non-infected cells than in infected cells. Interestingly, cells infected with the TK- strain have a tenfold higher phosphorylating capacity than normal, uninfected cells, a fact which might indicate that host cell deoxythymidine kinase is induced during HSV infection. AraTMP is incorporated into cellular DNA but not into HSV DNA. This finding is in contrast to observations with arabinofuranosyladenine, which is incorporated into both cellular and HSV DNA. In vitro experiments with HSV-induced DNA polymerase show that araTTP strongly inhibits the enzyme activity. Therefore we conclude that the inhibition of HSV DNA polymerase by araTTP (formed intracellularly from araThd) is the explanation for the observed antiviral activity of araThd.", "contents": "Phosphorylation of arabinofuranosylthymine in non-infected and herpesvirus (TK+ and TK-)-infected cells. The phosphorylation of arabinofuranosylthymine (araThd) has been studied both in non-infected cells and in those infected with herpes simplex virus (HSV-1, Lennette; HSV-1, IES and HSV-2, D-316). In these experiments, HSV strains were used which either contain (Lennette, TK+ and D-316 TK+) or lack (IES, TK-) the capacity to induce pyrimidine deoxyribonucleoside kinase. It was found that extracellularly administered araThd is phosphorylated to ara TTP via araTMP and araTDP in both non-infected and in HSV-infected cells. The phosphorylating capacity is more than tenfold lower in non-infected cells than in infected cells. Interestingly, cells infected with the TK- strain have a tenfold higher phosphorylating capacity than normal, uninfected cells, a fact which might indicate that host cell deoxythymidine kinase is induced during HSV infection. AraTMP is incorporated into cellular DNA but not into HSV DNA. This finding is in contrast to observations with arabinofuranosyladenine, which is incorporated into both cellular and HSV DNA. In vitro experiments with HSV-induced DNA polymerase show that araTTP strongly inhibits the enzyme activity. Therefore we conclude that the inhibition of HSV DNA polymerase by araTTP (formed intracellularly from araThd) is the explanation for the observed antiviral activity of araThd."}
{"id": "PMID:225423", "title": "Recovery of three distinct biologically active type C viruses from cloned C57Bl/6 melanoma cells.", "content": "The genome of a single cell derived from the B16 melanoma contains information for the expression of three distinct biologically active viruses: the N- and B-tropic ecotropic viruses and the xenotropic virus. Their release results in reduction of melanin production. A possible relationship of virus replication to differentiation may be involved.", "contents": "Recovery of three distinct biologically active type C viruses from cloned C57Bl/6 melanoma cells. The genome of a single cell derived from the B16 melanoma contains information for the expression of three distinct biologically active viruses: the N- and B-tropic ecotropic viruses and the xenotropic virus. Their release results in reduction of melanin production. A possible relationship of virus replication to differentiation may be involved."}
{"id": "PMID:225424", "title": "Polypeptides of bovine rotavirus.", "content": "Polyacrylamide gel electrophoresis of bovine rotavirus or neonatal calf diarrhoea virus (NCDV) grown in cell culture resolved eight species of polypeptide. The inner shell particles contained five polypeptides and the outer shell three polypeptides. A major polypeptide of the outer shell was glycosylated. The infectivity of NCDV was enhanced by treatment with trypsin in vitro. All eight polypeptides were affected by trypsin treatment as judged by diminished intensity of polypeptide bands by radiography and several new bands appeared. The intracellular synthesis of NCDV polypeptides was studied by pulse and pulse-chase experiments. Infected cells contained all eight virus capsid proteins and, in addition, three presumably virus-specific polypeptides which were non-capsid polypeptides (NCVP). There was no evidence that any of these polypeptides was processed after synthesis. It is suggested, therefore, that all these polypeptides are primary gene products.", "contents": "Polypeptides of bovine rotavirus. Polyacrylamide gel electrophoresis of bovine rotavirus or neonatal calf diarrhoea virus (NCDV) grown in cell culture resolved eight species of polypeptide. The inner shell particles contained five polypeptides and the outer shell three polypeptides. A major polypeptide of the outer shell was glycosylated. The infectivity of NCDV was enhanced by treatment with trypsin in vitro. All eight polypeptides were affected by trypsin treatment as judged by diminished intensity of polypeptide bands by radiography and several new bands appeared. The intracellular synthesis of NCDV polypeptides was studied by pulse and pulse-chase experiments. Infected cells contained all eight virus capsid proteins and, in addition, three presumably virus-specific polypeptides which were non-capsid polypeptides (NCVP). There was no evidence that any of these polypeptides was processed after synthesis. It is suggested, therefore, that all these polypeptides are primary gene products."}
{"id": "PMID:225425", "title": "Isolation and characterization of trypsin-resistant O1 variants of foot-and-mouth disease virus.", "content": "Strains of foot-and-mouth disease virus of types O1 and A10 were isolated which showed no significant loss of infectivity upon trypsinization. These 'trypsin-resistant' (TR) viruses were obtained by serial passage in BHK cells of virus that was trypsin-treated before inoculation of the cells. Three O1 isolates were cloned and studied further. Cell attachment of those TR O1 variants (OTR1) was not reduced by trypsinization, unlike that of parent virus. The polypeptide compositions of TR viruses as determined by SDS-polyacrylamide gel electrophoresis were identical with those of parent virus, with the exception of OTR1 which contained an additional polypeptide approx, 3000 daltons larger than VP1. After trypsinization, which normally cleaves VP1, the polypeptide composition of the three TR viruses (including OTR1) and of parent virus did not show any significant difference. In OTR1 both the additional virus protein and VP1 were cleaved into a P18 molecule and smaller fragments. The surface location of this additional polypeptide was confirmed by iodination experiments. It was shown by immunodiffusion experiments that only OTR1 differed from the parent virus. This antigenic change was present on the trypsin-sensitive part of the virus since trypsinized TR viruses (including OTR1) were antigenically identical to trypsinized parent virus. The electrophoretic mobilities of the three OTR viruses isolated, and of parent virus, differed somewhat before trypsinization. After trypsin-treatment, the mobilities of TR viruses were all increased to the same level; however, their rate of migration was lower than that of trypsin-treated parent virus. This lower mobility of trypsin-treated OTR viruses was the only difference which could be associated with retained infectivity.", "contents": "Isolation and characterization of trypsin-resistant O1 variants of foot-and-mouth disease virus. Strains of foot-and-mouth disease virus of types O1 and A10 were isolated which showed no significant loss of infectivity upon trypsinization. These 'trypsin-resistant' (TR) viruses were obtained by serial passage in BHK cells of virus that was trypsin-treated before inoculation of the cells. Three O1 isolates were cloned and studied further. Cell attachment of those TR O1 variants (OTR1) was not reduced by trypsinization, unlike that of parent virus. The polypeptide compositions of TR viruses as determined by SDS-polyacrylamide gel electrophoresis were identical with those of parent virus, with the exception of OTR1 which contained an additional polypeptide approx, 3000 daltons larger than VP1. After trypsinization, which normally cleaves VP1, the polypeptide composition of the three TR viruses (including OTR1) and of parent virus did not show any significant difference. In OTR1 both the additional virus protein and VP1 were cleaved into a P18 molecule and smaller fragments. The surface location of this additional polypeptide was confirmed by iodination experiments. It was shown by immunodiffusion experiments that only OTR1 differed from the parent virus. This antigenic change was present on the trypsin-sensitive part of the virus since trypsinized TR viruses (including OTR1) were antigenically identical to trypsinized parent virus. The electrophoretic mobilities of the three OTR viruses isolated, and of parent virus, differed somewhat before trypsinization. After trypsin-treatment, the mobilities of TR viruses were all increased to the same level; however, their rate of migration was lower than that of trypsin-treated parent virus. This lower mobility of trypsin-treated OTR viruses was the only difference which could be associated with retained infectivity."}
{"id": "PMID:225426", "title": "Comparison of the suppression of cell and virus growth in transformed human cells of leukocyte and fibroblast interferon.", "content": "The effects of human leukocyte interferon (Le-IF) and fibroblast interferon (F-IF) on the growth of the transformed human cell lines, RSa and RSb, were compared. Both were considerably more sensitive to F-IF than to Le-IF. Two cell lines, IFr and F-IFr, derived from the RSa cell line, were resistant to the anticellular effects of Le-IF, but less resistant to those of F-IF.", "contents": "Comparison of the suppression of cell and virus growth in transformed human cells of leukocyte and fibroblast interferon. The effects of human leukocyte interferon (Le-IF) and fibroblast interferon (F-IF) on the growth of the transformed human cell lines, RSa and RSb, were compared. Both were considerably more sensitive to F-IF than to Le-IF. Two cell lines, IFr and F-IFr, derived from the RSa cell line, were resistant to the anticellular effects of Le-IF, but less resistant to those of F-IF."}
{"id": "PMID:225427", "title": "Inhibition of 80S initiation complex formation by infection with poliovirus.", "content": "Anisomycin has been shown to stabilize ribosome initiation complexes containing messenger RNA and met-tRNAf met to high salt conditions. Extracts from HeLa cells treated with 5 X 10(-7) M-anisomycin for 15 min accumulate 80S initiation complexes which can be detected by their absorbance in sucrose gradients. Poliovirus-infected cells fail to form the 80S initiation complex early after infection, when inhibition of host cell protein synthesis occurs. These complexes re-form later in infection after virus RNA is synthesized. No re-formation occurs in the absence of virus replication. Thus, the step in protein synthesis inhibited by poliovirus precedes the entry of components into the 80S initiation complex.", "contents": "Inhibition of 80S initiation complex formation by infection with poliovirus. Anisomycin has been shown to stabilize ribosome initiation complexes containing messenger RNA and met-tRNAf met to high salt conditions. Extracts from HeLa cells treated with 5 X 10(-7) M-anisomycin for 15 min accumulate 80S initiation complexes which can be detected by their absorbance in sucrose gradients. Poliovirus-infected cells fail to form the 80S initiation complex early after infection, when inhibition of host cell protein synthesis occurs. These complexes re-form later in infection after virus RNA is synthesized. No re-formation occurs in the absence of virus replication. Thus, the step in protein synthesis inhibited by poliovirus precedes the entry of components into the 80S initiation complex."}
{"id": "PMID:225428", "title": "Reversion of Kirsten sarcoma virus transformed human cells: elimination of the sarcoma virus nucleotide sequences.", "content": "The virus-specific nucleotide sequences in the RNA and DNA of a Kirsten mouse sarcoma virus (Ki-MSV)-transformed non-producer human osteosarcoma cell clone and two subclones of these cells that reverted to a normal phenotype have been analysed by hybridization of sarcoma virus-specific complementary DNA (cDNA) to cellular RNA or DNA. Whereas the transformed clone had acquired de novo Ki-MSV sequences in the RNA and DNA of the cells, both the revertant cell lines seemed to have lost most or all of this information from the cellular nucleic acids. The DNA from the revertant cells lacked the sequences represented either in the Ki-MSV-specific cDNA or in the total cDNA of the leukaemia-sarcoma virus complex. Thus, the reversion of the virus-transformed human cells to normal morphology is associated with the loss of most or all of the proviral sequences from the cellular DNA.", "contents": "Reversion of Kirsten sarcoma virus transformed human cells: elimination of the sarcoma virus nucleotide sequences. The virus-specific nucleotide sequences in the RNA and DNA of a Kirsten mouse sarcoma virus (Ki-MSV)-transformed non-producer human osteosarcoma cell clone and two subclones of these cells that reverted to a normal phenotype have been analysed by hybridization of sarcoma virus-specific complementary DNA (cDNA) to cellular RNA or DNA. Whereas the transformed clone had acquired de novo Ki-MSV sequences in the RNA and DNA of the cells, both the revertant cell lines seemed to have lost most or all of this information from the cellular nucleic acids. The DNA from the revertant cells lacked the sequences represented either in the Ki-MSV-specific cDNA or in the total cDNA of the leukaemia-sarcoma virus complex. Thus, the reversion of the virus-transformed human cells to normal morphology is associated with the loss of most or all of the proviral sequences from the cellular DNA."}
{"id": "PMID:225429", "title": "Polypeptides of simian rotavirus (SA-11) determined by a continuous polyacrylamide gel electrophoresis method.", "content": "Simian rotavirus (SA-11) isolated from infected African green monkey kidney cells was separated into two virus fractions in a CsCl density gradient and their proteins analysed on a continuous phosphte buffered polyacrylamide gel electrophoresis system. One peak (buoyant density 1.37 g/ml) contained double capsid virus particles which were radioimmunoassay (RIA)- and haemagglutinin (HA)- positive and yielded eight polypeptides whose mol. wt. ranged from 48,000 to 128,000. The second peak (buoyant density 1.39 g/ml) which contained 70% single capsid particles and was RIA-positive but HA-negative, yielded only five polypeptides. The three polypeptides missing in the second peak are associated presumably with the outer capsid of SA-11 virus particles and one or more of these is assumed to be the HA of SA-11 rotavirus.", "contents": "Polypeptides of simian rotavirus (SA-11) determined by a continuous polyacrylamide gel electrophoresis method. Simian rotavirus (SA-11) isolated from infected African green monkey kidney cells was separated into two virus fractions in a CsCl density gradient and their proteins analysed on a continuous phosphte buffered polyacrylamide gel electrophoresis system. One peak (buoyant density 1.37 g/ml) contained double capsid virus particles which were radioimmunoassay (RIA)- and haemagglutinin (HA)- positive and yielded eight polypeptides whose mol. wt. ranged from 48,000 to 128,000. The second peak (buoyant density 1.39 g/ml) which contained 70% single capsid particles and was RIA-positive but HA-negative, yielded only five polypeptides. The three polypeptides missing in the second peak are associated presumably with the outer capsid of SA-11 virus particles and one or more of these is assumed to be the HA of SA-11 rotavirus."}
{"id": "PMID:225430", "title": "Further characterization of herpes virus persistence.", "content": "Infection of cell cultures with herpes simples virus type 1 (HSV-1) under standard culture conditions yielded persistently infected cells capable of continued growth in the presence of virus and of forming colonies in agarose. The ability of an infected culture to yield cells able to survive HSV-1 infection was directly related to the presence of S phase cells (cells actively engaged in DNA synthesis) at the time of infection. Only when very high multiplicities of infecting virus (greater than 10) were used did cultures fail to yield persistently infected cells capable of colonial growth in agarose. Cell clones derived from colonies grown in agarose established cell cultures which possessed all the characteristics of HSV-1 persistently infected cultures. When cultures were cloned a second time in agarose, as a rare event, cell cultures which did not immediately liberate infectious virus could be isolated. These cell cultures, however, possessed an increased resistance to superinfection by HSV-1. On continued cultivation they reverted to persistence as exhibited by the sudden onset of virus cytopathic effects and release of infectious virus.", "contents": "Further characterization of herpes virus persistence. Infection of cell cultures with herpes simples virus type 1 (HSV-1) under standard culture conditions yielded persistently infected cells capable of continued growth in the presence of virus and of forming colonies in agarose. The ability of an infected culture to yield cells able to survive HSV-1 infection was directly related to the presence of S phase cells (cells actively engaged in DNA synthesis) at the time of infection. Only when very high multiplicities of infecting virus (greater than 10) were used did cultures fail to yield persistently infected cells capable of colonial growth in agarose. Cell clones derived from colonies grown in agarose established cell cultures which possessed all the characteristics of HSV-1 persistently infected cultures. When cultures were cloned a second time in agarose, as a rare event, cell cultures which did not immediately liberate infectious virus could be isolated. These cell cultures, however, possessed an increased resistance to superinfection by HSV-1. On continued cultivation they reverted to persistence as exhibited by the sudden onset of virus cytopathic effects and release of infectious virus."}
{"id": "PMID:225431", "title": "In vitro transformation by bovine papilloma virus.", "content": "This paper reports the development of a quantal transformation assay for bovine papillome virus. Support for its specificity to fibropapilloma derived bovine papilloma virus comes from (I) the absence of transformation associated changes following inoculations of normal bovine skin, bovine teat papilloma, bovine teat focal epithelial hyperplasia lesion and canine papilloma derived suspensions; (2) in vitro transformation occurs when CsCl purified fibropapilloma-derived BPV is used; (3) in vitro transformation experiments reported here parallel in vivo transmission of fibropapillomas described elsewhere using the same extracts; (4) the time-temperature inactivation of BPV using in vitro transformation parallels in vivo results and is similar to that reported for other papovaviruses; (5) BPV in vitro transformed cells are tumorigenic in nude mice and increase in vivo resistance in calves to subsequent challenge with fibropapilloma derived virus; (6) inhibition of in vitro transformation by bovine papilloma virus occurs when sera from calves bearing regressing fibropapillomas are used in conjunction with complement; (7) transformation inhibition activity may be adsorbed from high titre sera using BPV-induced tumour cells or in vitro transformed cells but not using various virus suspensions. The detection of BPV in commercially available milk is reported. While it is highly likely that milk-derived BPV is active, no direct evidence is available since the vast majority of teat lesions contain papilloma and focal epithelial hyperplasia-derived BPV which neither transform cultures in vitro, nor produce fibropapillomas in vivo. The work reported here lends further support for the existence of several types of BPV suggested elsewhere.", "contents": "In vitro transformation by bovine papilloma virus. This paper reports the development of a quantal transformation assay for bovine papillome virus. Support for its specificity to fibropapilloma derived bovine papilloma virus comes from (I) the absence of transformation associated changes following inoculations of normal bovine skin, bovine teat papilloma, bovine teat focal epithelial hyperplasia lesion and canine papilloma derived suspensions; (2) in vitro transformation occurs when CsCl purified fibropapilloma-derived BPV is used; (3) in vitro transformation experiments reported here parallel in vivo transmission of fibropapillomas described elsewhere using the same extracts; (4) the time-temperature inactivation of BPV using in vitro transformation parallels in vivo results and is similar to that reported for other papovaviruses; (5) BPV in vitro transformed cells are tumorigenic in nude mice and increase in vivo resistance in calves to subsequent challenge with fibropapilloma derived virus; (6) inhibition of in vitro transformation by bovine papilloma virus occurs when sera from calves bearing regressing fibropapillomas are used in conjunction with complement; (7) transformation inhibition activity may be adsorbed from high titre sera using BPV-induced tumour cells or in vitro transformed cells but not using various virus suspensions. The detection of BPV in commercially available milk is reported. While it is highly likely that milk-derived BPV is active, no direct evidence is available since the vast majority of teat lesions contain papilloma and focal epithelial hyperplasia-derived BPV which neither transform cultures in vitro, nor produce fibropapillomas in vivo. The work reported here lends further support for the existence of several types of BPV suggested elsewhere."}
{"id": "PMID:225432", "title": "A plaque assay for the simian rotavirus SAII.", "content": "A sensitive, quantitative and reproducible plaque assay for the measurement of the simian rotavirus SAII is described. Plaque formation required the presence of the facilitators pancreatin or trypsin and diethylaminoethyl-dextran in the agar overlay. SAII produced plaques in three continuous primate cell lines: MA-104, CV-1 and LLC-MK2. MA-104 cells were the most sensitive.", "contents": "A plaque assay for the simian rotavirus SAII. A sensitive, quantitative and reproducible plaque assay for the measurement of the simian rotavirus SAII is described. Plaque formation required the presence of the facilitators pancreatin or trypsin and diethylaminoethyl-dextran in the agar overlay. SAII produced plaques in three continuous primate cell lines: MA-104, CV-1 and LLC-MK2. MA-104 cells were the most sensitive."}
{"id": "PMID:225433", "title": "Relationship between single-stranded DNA isolated from mouse cells transformed by simian virus 40 and transcription of cellular and virus genes.", "content": "A minor fraction of single-stranded DNA (ssDNA) was isolated by an improved method of hydroxylapatite chromatography (HAC) from the native nuclear DNA (nDNA) of SV--3T3 cells, non-productively transformed by SV40. Molecular hybridization, monitored by the use of S1 nuclease, HAC, isopycnic centrifugation and thermal melting showed that ssDNA from SV-3T3 cells (which amounts to 1.5 to 2% of the total nDNA) has the same characteristics as ssDNA previously isolated from other cell species. Only 27 to 28% of ssDNA can be self-hybridized but the greatest part can be reassociated to the non-repetitive portion of nDNA and up to 38% hybridized to homologous RNAs, as compared with 7 to 8% for bulk nDNA. Highly radioactive virus probes (SV40-3H-cRNA synthesized in a cell-free system and the separated 'early' and 'late' strands of SV40 DNA labelled with 125I) were annealed to different excess amounts of cellular DNA. Both the quantities of each probe hybridized at saturation levels and the various reaction kinetics indicated that ssDNA is greatly enriched for virus sequences, mainly originating from the 'early' DNA strand which is predominantly expressed in SV-3T3 cells. The mode of formation of ssDNA is discussed in the light of other findings on the effects of DNA untwisting proteins and susceptibility of active animal genes to selective enzymic attacks.", "contents": "Relationship between single-stranded DNA isolated from mouse cells transformed by simian virus 40 and transcription of cellular and virus genes. A minor fraction of single-stranded DNA (ssDNA) was isolated by an improved method of hydroxylapatite chromatography (HAC) from the native nuclear DNA (nDNA) of SV--3T3 cells, non-productively transformed by SV40. Molecular hybridization, monitored by the use of S1 nuclease, HAC, isopycnic centrifugation and thermal melting showed that ssDNA from SV-3T3 cells (which amounts to 1.5 to 2% of the total nDNA) has the same characteristics as ssDNA previously isolated from other cell species. Only 27 to 28% of ssDNA can be self-hybridized but the greatest part can be reassociated to the non-repetitive portion of nDNA and up to 38% hybridized to homologous RNAs, as compared with 7 to 8% for bulk nDNA. Highly radioactive virus probes (SV40-3H-cRNA synthesized in a cell-free system and the separated 'early' and 'late' strands of SV40 DNA labelled with 125I) were annealed to different excess amounts of cellular DNA. Both the quantities of each probe hybridized at saturation levels and the various reaction kinetics indicated that ssDNA is greatly enriched for virus sequences, mainly originating from the 'early' DNA strand which is predominantly expressed in SV-3T3 cells. The mode of formation of ssDNA is discussed in the light of other findings on the effects of DNA untwisting proteins and susceptibility of active animal genes to selective enzymic attacks."}
{"id": "PMID:225434", "title": "Presence of virus-specific DNA sequences in murine type C viruses.", "content": "Total nucleic acids prepared from a number of murine retroviruses have been shown to contain virus-specific DNA in addition to genomic RNA. This virus-specific DNA has been shown to be at least partially double stranded and to be present within the virus core particle. The DNA isolated from the virus is greatly enriched in virus-specific DNA relative to that from virus infected cells.", "contents": "Presence of virus-specific DNA sequences in murine type C viruses. Total nucleic acids prepared from a number of murine retroviruses have been shown to contain virus-specific DNA in addition to genomic RNA. This virus-specific DNA has been shown to be at least partially double stranded and to be present within the virus core particle. The DNA isolated from the virus is greatly enriched in virus-specific DNA relative to that from virus infected cells."}
{"id": "PMID:225435", "title": "Mechanism of host restriction of adenovirus-associated virus replication in African green monkey kidney cells.", "content": "Human adenovirus (Ad) serotypes provide an early factor(s) that is necessary for adenovirus-associated virus (AAV) multiplication in human cell lines. However, little, if any, AAV production occurs in primary African green monkey kidney (AGMK) cells co-infected with AAV and a helper human Ad (non-permissive infection), unless cells are additionally infected with SV40 (permissive infection). To determine the basis of the host restriction of AAV replication in AGMK cells, AAV DNA, RNA and protein synthesis were analyzed under various conditions of infection. Hybridization reactions revealed no detectable AAV-specific DNA or RNA in infections with AAV alone or in combination with SV40. In co-infections with AAV and Ad5 or Ad7, the synthesis of both AAV- and Ad-specific DNA and RNA occurred without a significant rise in titre of either virus. During non-permissive infection, however, AAV DNA synthesis was abnormal in that an expected accumulation of single-stranded progeny molecules was not observed. Finally, although intact 20S AAV transcripts were present in the cytoplasm of AGMK cells during non-permissive infection (in amounts ranging from 50 to 80% of that found during permissive infection), AAV-specific polypeptides were not demonstrable by polyacrylamide gel electrophoresis. Taken together, these experiments indicate that the host restriction of AAV replication in AGMK cells is exerted at the level of translation of the single AAV messenger RNA. In addition, it appears that one or more of the AAV polypeptides specified by this message is required for the production of single-stranded AAV progeny DNA.", "contents": "Mechanism of host restriction of adenovirus-associated virus replication in African green monkey kidney cells. Human adenovirus (Ad) serotypes provide an early factor(s) that is necessary for adenovirus-associated virus (AAV) multiplication in human cell lines. However, little, if any, AAV production occurs in primary African green monkey kidney (AGMK) cells co-infected with AAV and a helper human Ad (non-permissive infection), unless cells are additionally infected with SV40 (permissive infection). To determine the basis of the host restriction of AAV replication in AGMK cells, AAV DNA, RNA and protein synthesis were analyzed under various conditions of infection. Hybridization reactions revealed no detectable AAV-specific DNA or RNA in infections with AAV alone or in combination with SV40. In co-infections with AAV and Ad5 or Ad7, the synthesis of both AAV- and Ad-specific DNA and RNA occurred without a significant rise in titre of either virus. During non-permissive infection, however, AAV DNA synthesis was abnormal in that an expected accumulation of single-stranded progeny molecules was not observed. Finally, although intact 20S AAV transcripts were present in the cytoplasm of AGMK cells during non-permissive infection (in amounts ranging from 50 to 80% of that found during permissive infection), AAV-specific polypeptides were not demonstrable by polyacrylamide gel electrophoresis. Taken together, these experiments indicate that the host restriction of AAV replication in AGMK cells is exerted at the level of translation of the single AAV messenger RNA. In addition, it appears that one or more of the AAV polypeptides specified by this message is required for the production of single-stranded AAV progeny DNA."}
{"id": "PMID:225436", "title": "Phenotypic mixing between murine oncoviruses and murine cytomegalovirus.", "content": "In vitro interactions between murine cytomegalovirus (MCMV) and murine leukaemia viruses (MuLV), two groups of enveloped viruses capable of causing persistent or latent infections in vivo, were examined for evidence of phenotypic mixing. The growth of MCMV in murine cells productively infected with ecotropic MuLV was shown to result regularly in the production of phenotypically mixed particles having the envelope antigens of MuLV and the genome of MCMV [MCMV(MuLV) pseudotypes]. The identity of such pseudotype particles was confirmed by the use of specific anti-MuLV serum and by the demonstration of restriction due to viral interference of penetration of these particles on MuLV-infected murine cells. This restriction was independent of N- or B-tropism. The production of reverse pseudotypes could not be examined because of the lytic effects of MCMV on the requisite assay cells.", "contents": "Phenotypic mixing between murine oncoviruses and murine cytomegalovirus. In vitro interactions between murine cytomegalovirus (MCMV) and murine leukaemia viruses (MuLV), two groups of enveloped viruses capable of causing persistent or latent infections in vivo, were examined for evidence of phenotypic mixing. The growth of MCMV in murine cells productively infected with ecotropic MuLV was shown to result regularly in the production of phenotypically mixed particles having the envelope antigens of MuLV and the genome of MCMV [MCMV(MuLV) pseudotypes]. The identity of such pseudotype particles was confirmed by the use of specific anti-MuLV serum and by the demonstration of restriction due to viral interference of penetration of these particles on MuLV-infected murine cells. This restriction was independent of N- or B-tropism. The production of reverse pseudotypes could not be examined because of the lytic effects of MCMV on the requisite assay cells."}
{"id": "PMID:225437", "title": "SV40-related T-antigen expression in human meningiomas with normal and G-22-monosomic karyotype.", "content": "Six of 16 meningiomas tested in early subcultures by indirect immunofluorescence showed SV40 T-antigen. Two different antisera specific for T-antigen were used. One serum gave a positive reaction with six tumours and the other with only two. In one T-antigen positive meningioma, the typical nuclear fluorescence changed, beginning with the second subculture, into an unusual brilliant granular pattern irregularly distributed over the nuclei. In six meningiomas, a specific chromosome aberration (monosomy G 22) was established. However, up to now, no clear correlation between karyotype and T-antigen expression could be found: cells from three meningiomas with positive reactions had normal karyotypes, whereas those from three tumours with typical chromosome loss showed no T-antigen.", "contents": "SV40-related T-antigen expression in human meningiomas with normal and G-22-monosomic karyotype. Six of 16 meningiomas tested in early subcultures by indirect immunofluorescence showed SV40 T-antigen. Two different antisera specific for T-antigen were used. One serum gave a positive reaction with six tumours and the other with only two. In one T-antigen positive meningioma, the typical nuclear fluorescence changed, beginning with the second subculture, into an unusual brilliant granular pattern irregularly distributed over the nuclei. In six meningiomas, a specific chromosome aberration (monosomy G 22) was established. However, up to now, no clear correlation between karyotype and T-antigen expression could be found: cells from three meningiomas with positive reactions had normal karyotypes, whereas those from three tumours with typical chromosome loss showed no T-antigen."}
{"id": "PMID:225438", "title": "Selective transcription of genomic sequences common to both N- and X-tropic endogenous retroviruses in BALB/c mouse tissues.", "content": "Total RNAs from four BALB/c mouse tissues, containing mostly non-dividing cells (liver and kidney) or variable proportions of dividing cells (uterus and embryo) were analysed for sequences complementary to 3H-DNA transcripts synthesized from BALB/c endogenous. N- and X-tropic retroviruses. Extensive transcription of virogene information was detected in the tissues examined, but such transcription was found to be mostly limited to the homologous regions of the two virus genomes. No additivity of hybridization values could be detected when RNAs from two different tissues were mixed, which suggests that BALB/c mouse liver, kidney, uterus and embryo transcribe a common set of nucleic acid sequences of the homologous regions of the N- and X-tropic viral genomes, in addition to other sequences of the same region that are specific for indiviual tissues.", "contents": "Selective transcription of genomic sequences common to both N- and X-tropic endogenous retroviruses in BALB/c mouse tissues. Total RNAs from four BALB/c mouse tissues, containing mostly non-dividing cells (liver and kidney) or variable proportions of dividing cells (uterus and embryo) were analysed for sequences complementary to 3H-DNA transcripts synthesized from BALB/c endogenous. N- and X-tropic retroviruses. Extensive transcription of virogene information was detected in the tissues examined, but such transcription was found to be mostly limited to the homologous regions of the two virus genomes. No additivity of hybridization values could be detected when RNAs from two different tissues were mixed, which suggests that BALB/c mouse liver, kidney, uterus and embryo transcribe a common set of nucleic acid sequences of the homologous regions of the N- and X-tropic viral genomes, in addition to other sequences of the same region that are specific for indiviual tissues."}
{"id": "PMID:225439", "title": "A simple immunofluorescent technique for the detection of human rotavirus.", "content": "If trypsin is incorporated in the tissue culture medium it is possible to carry out a sensitive immunofluorescence assay for the presence of human rotavirus. The enhanced effect of trypsin is negated by serum. It has also been established that naturally occurring enzymes in faeces enable some virus to penetrate tissue culture cells. The role of these naturally occurring enzymes in the pathogenesis of rotavirus infection is discussed.", "contents": "A simple immunofluorescent technique for the detection of human rotavirus. If trypsin is incorporated in the tissue culture medium it is possible to carry out a sensitive immunofluorescence assay for the presence of human rotavirus. The enhanced effect of trypsin is negated by serum. It has also been established that naturally occurring enzymes in faeces enable some virus to penetrate tissue culture cells. The role of these naturally occurring enzymes in the pathogenesis of rotavirus infection is discussed."}
{"id": "PMID:225440", "title": "The stability of herpes simplex virus on vaginal tampons.", "content": "Herpes simplex virus can be quantitatively recovered from vaginal tampons suspended in tissue culture medium and stored over a wide range of temperatures. Because herpes simplex virus is stable for several days with refrigeration or after freezing, this method of culture of cervicovaginal virus lends itself to epidemiologic studies.", "contents": "The stability of herpes simplex virus on vaginal tampons. Herpes simplex virus can be quantitatively recovered from vaginal tampons suspended in tissue culture medium and stored over a wide range of temperatures. Because herpes simplex virus is stable for several days with refrigeration or after freezing, this method of culture of cervicovaginal virus lends itself to epidemiologic studies."}
{"id": "PMID:225441", "title": "Properties of coxsackievirus B3 variants which are amyocarditic or myocarditic for mice.", "content": "Inoculation of adolescent CD-1 mice with one variant of coxsackievirus B3 (CVB3m) results in induction of readily observable myocardial lesions, whereas inoculation of siblings with a second variant (CVB3o) results in little or no myocarditis. These variants could not be distinquished from each other on the basis of replication properties in HeLa cells or cardiac tissues in vivo, sensitivity to human interferon in HeLa cells, induction of interferon in the mouse, generation of detectable levels of defective-interfering particles in HeLa cells or in cardiac tissue in vivo, stimulation of serum-neutralizing antibody titers, nor in their rate of clearance by the spleen. Infectivity of CVB3o was slightly more heat labile at 34 degrees C than CVB3m. Little if any replication of either CVB3o or CVB3m occurred in either adherent or nonadherent populations of normal murine lymphoid cells. Cardiac tissues from mice inoculated with CVB3m but not CVBo contain new antigens that can inhibit migration of sensitized lymphocytes from CVB3m-immunized mice in an in vitro cell-migration-inhibition assay. However, the CVB3o variant was shown to have the genetic capability of inducing myocarditis if the mice were treated with cyclophosphamide prior to virus inoculation. These results suggest, in agreement with our previously published work, that induction of myocarditis by CVB3 requires destruction of myocytes by virus and subsequent stimulation of cell-mediated responses to new antigens produced in the myocardium during virus replication.", "contents": "Properties of coxsackievirus B3 variants which are amyocarditic or myocarditic for mice. Inoculation of adolescent CD-1 mice with one variant of coxsackievirus B3 (CVB3m) results in induction of readily observable myocardial lesions, whereas inoculation of siblings with a second variant (CVB3o) results in little or no myocarditis. These variants could not be distinquished from each other on the basis of replication properties in HeLa cells or cardiac tissues in vivo, sensitivity to human interferon in HeLa cells, induction of interferon in the mouse, generation of detectable levels of defective-interfering particles in HeLa cells or in cardiac tissue in vivo, stimulation of serum-neutralizing antibody titers, nor in their rate of clearance by the spleen. Infectivity of CVB3o was slightly more heat labile at 34 degrees C than CVB3m. Little if any replication of either CVB3o or CVB3m occurred in either adherent or nonadherent populations of normal murine lymphoid cells. Cardiac tissues from mice inoculated with CVB3m but not CVBo contain new antigens that can inhibit migration of sensitized lymphocytes from CVB3m-immunized mice in an in vitro cell-migration-inhibition assay. However, the CVB3o variant was shown to have the genetic capability of inducing myocarditis if the mice were treated with cyclophosphamide prior to virus inoculation. These results suggest, in agreement with our previously published work, that induction of myocarditis by CVB3 requires destruction of myocytes by virus and subsequent stimulation of cell-mediated responses to new antigens produced in the myocardium during virus replication."}
{"id": "PMID:225442", "title": "Fusion of cytomegalovirus infected fibroblasts to form multinucleate giant cells.", "content": "Multinucleate giant cells have been observed to arise by cell fusion in cultures of human embryonic fibroblasts infected with human cytomegalovirus (CMV), strain AD 169. The infected cells develope intranuclear and intracytoplasmic inclusions and began to fuse three to four days postinfection when the majority of the cells were showing signs of a cytopathic effect.", "contents": "Fusion of cytomegalovirus infected fibroblasts to form multinucleate giant cells. Multinucleate giant cells have been observed to arise by cell fusion in cultures of human embryonic fibroblasts infected with human cytomegalovirus (CMV), strain AD 169. The infected cells develope intranuclear and intracytoplasmic inclusions and began to fuse three to four days postinfection when the majority of the cells were showing signs of a cytopathic effect."}
{"id": "PMID:225443", "title": "Solid-phase radioimmunoassay of IgA, IgG, and IgM antibodies to human rotavirus.", "content": "A solid-phase radioimmunoassay (RIA) has been developed for the detection of human rotavirus-specific IgA, IgG, and IgM antibodies. Nebraska calf diarrhea virus grown in LLC-MK2 cell cultures in the presence of trypsin was directly adsorbed onto polystyrene balls, and antibodies that attached to the virus-coated balls were detected by subsequent binding of 125I-labeled antibodies specific to human alpha, gamma or mu chains of human Iga, IgG, or IgM immunoglobulins. A total of 116 serum specimens from 58 adult patients were tested. Binding ratios between the positive and the negative serum varied between 5 and 15, occasionally being 20 or more in the IgA and IgG assays, but rarely exceeding 3 in the IgM assay. The RIA was found to be more sensitive in detecting antibodies to rotavirus than the complement fixation (CF) test, the RIA titers obtained being 50--100 times as high as the CF titers. The method described offers a possibility of evaluating the immune response to human rotavirus and of detecting recent infection.", "contents": "Solid-phase radioimmunoassay of IgA, IgG, and IgM antibodies to human rotavirus. A solid-phase radioimmunoassay (RIA) has been developed for the detection of human rotavirus-specific IgA, IgG, and IgM antibodies. Nebraska calf diarrhea virus grown in LLC-MK2 cell cultures in the presence of trypsin was directly adsorbed onto polystyrene balls, and antibodies that attached to the virus-coated balls were detected by subsequent binding of 125I-labeled antibodies specific to human alpha, gamma or mu chains of human Iga, IgG, or IgM immunoglobulins. A total of 116 serum specimens from 58 adult patients were tested. Binding ratios between the positive and the negative serum varied between 5 and 15, occasionally being 20 or more in the IgA and IgG assays, but rarely exceeding 3 in the IgM assay. The RIA was found to be more sensitive in detecting antibodies to rotavirus than the complement fixation (CF) test, the RIA titers obtained being 50--100 times as high as the CF titers. The method described offers a possibility of evaluating the immune response to human rotavirus and of detecting recent infection."}
{"id": "PMID:225444", "title": "Identification of an enteric adenovirus by immunoelectroosmophoresis (IEOP) technique.", "content": "Infantile gastroenteritis can be caused by several of the established adenovirus types. There are also adenoviruses that defy in vitro cultivation but have been recognized by electron microscopy. One isolate of these viruses, which have been designated enteric adenoviruses, has been characterized. Several of the established adenovirus types are shed in stools over long periods. The conditions for direct identification of enteric adenoviruses by immunoelectroosmophoresis (IEOP) have therefore been evaluated. Application of this technique requires highly specific reagents. However, a high prevalence of antibodies in rabbits reacting with human rotavirus was noted. For these reasons, immunoadsorbent purified antibodies were prepared. Because of the difficulty in purifying immunogens from stools, an immunization procedure characterized by immunization with adenovirus subunits bound to affinity chromatography beads was elaborated. An identification procedure for adenoviruses causing infantile gastroenteritis based a) on IEOP using group-specific and monospecific antibodies and b) on the determination of the in vitro cultivatability is suggested.", "contents": "Identification of an enteric adenovirus by immunoelectroosmophoresis (IEOP) technique. Infantile gastroenteritis can be caused by several of the established adenovirus types. There are also adenoviruses that defy in vitro cultivation but have been recognized by electron microscopy. One isolate of these viruses, which have been designated enteric adenoviruses, has been characterized. Several of the established adenovirus types are shed in stools over long periods. The conditions for direct identification of enteric adenoviruses by immunoelectroosmophoresis (IEOP) have therefore been evaluated. Application of this technique requires highly specific reagents. However, a high prevalence of antibodies in rabbits reacting with human rotavirus was noted. For these reasons, immunoadsorbent purified antibodies were prepared. Because of the difficulty in purifying immunogens from stools, an immunization procedure characterized by immunization with adenovirus subunits bound to affinity chromatography beads was elaborated. An identification procedure for adenoviruses causing infantile gastroenteritis based a) on IEOP using group-specific and monospecific antibodies and b) on the determination of the in vitro cultivatability is suggested."}
{"id": "PMID:225445", "title": "Catecholamine and 5-hydroxytryptamine synthesis and metabolism following intracerebroventricular injection of dibutyryl cyclic AMP.", "content": "Two to seven days after bilateral implantation of polyethylene tubings into the lateral ventricles rats were injected intracerebroventricularly with dibutyryl cAMP or dibutyryl cGMP. The accumulation of dopa and 5-hydroxytryptophan after inhibition of the aromatic amino acid decarboxylase with 3-hydroxybenzylhyrazine HCl, served as a measure of catecholamine and 5-hydroxytryptamine synthesis in vivo. A dose of 100 microgram dibutyryl cAMP per rat but not dibutyryl cGMP increased the accumulation of dopa in all brain regions by 70 to 130%. Both nucleotides stimulated the formation of 5-hydroxytryptophan in the dopamine-rich part of the limbic system and diencephalon and in addition dibutyryl cAMP increased 5-hydroxytryptophan in C. striatum and cerebellum. Dibutyryl cAMP (25-200 microgram per rat) did not change the dopamine levels in the dopamine-rich parts of the brain but decreased the noradrenaline level of the C. striatum in a dose-dependent manner. The same doses of dibutyryl cAMP elevated the 5-hydroxytryptamine level in brain stem and the level of 5-hydroxyindole acetic acid in diencephalon and the limbic system. The disappearance of noradrenaline but not of dopamine after inhibition of catecholamine synthesis with alpha-methyl-p-tyrosine methylester HCl was accelerated in most brain regions. The data are compatible with the view that dibutyryl cAMP stimulates tyrosine and tryptophan hydroxylase directly. In addition, dibutyryl cAMP appears to enhance the utilization of noradrenaline but not that of dopamine. The increased utilization of 5-hydroxytryptamine may be restricted to the diencephalon and the limbic system.", "contents": "Catecholamine and 5-hydroxytryptamine synthesis and metabolism following intracerebroventricular injection of dibutyryl cyclic AMP. Two to seven days after bilateral implantation of polyethylene tubings into the lateral ventricles rats were injected intracerebroventricularly with dibutyryl cAMP or dibutyryl cGMP. The accumulation of dopa and 5-hydroxytryptophan after inhibition of the aromatic amino acid decarboxylase with 3-hydroxybenzylhyrazine HCl, served as a measure of catecholamine and 5-hydroxytryptamine synthesis in vivo. A dose of 100 microgram dibutyryl cAMP per rat but not dibutyryl cGMP increased the accumulation of dopa in all brain regions by 70 to 130%. Both nucleotides stimulated the formation of 5-hydroxytryptophan in the dopamine-rich part of the limbic system and diencephalon and in addition dibutyryl cAMP increased 5-hydroxytryptophan in C. striatum and cerebellum. Dibutyryl cAMP (25-200 microgram per rat) did not change the dopamine levels in the dopamine-rich parts of the brain but decreased the noradrenaline level of the C. striatum in a dose-dependent manner. The same doses of dibutyryl cAMP elevated the 5-hydroxytryptamine level in brain stem and the level of 5-hydroxyindole acetic acid in diencephalon and the limbic system. The disappearance of noradrenaline but not of dopamine after inhibition of catecholamine synthesis with alpha-methyl-p-tyrosine methylester HCl was accelerated in most brain regions. The data are compatible with the view that dibutyryl cAMP stimulates tyrosine and tryptophan hydroxylase directly. In addition, dibutyryl cAMP appears to enhance the utilization of noradrenaline but not that of dopamine. The increased utilization of 5-hydroxytryptamine may be restricted to the diencephalon and the limbic system."}
{"id": "PMID:225447", "title": "Graded synaptic interactions between local premotor interneurons of the locust.", "content": "1. Graded synaptic interactions are revealed between pairs of nonspiking, local interneurons in the metathroracic ganglion of the locust. These interneurons drive motor neurons innervating muscles of a hindleg. 2. All the interactions found between the interneurons are inhibitory and one way. Synaptic transmission is effected by the graded release of chemical transmitter. Some of the connections are apparently direct. One local interneuron can, therefore, exert a graded control over the membrane potential of another local interneuron. 3. There are inhibitory connections between local interneurons that excite the same motor neuron, between local interneurons that excite antagonistic motor neurons, and between local interneurons that excite motor neurons to muscles moving different joints of a hindleg. 4. Other pairs of interneurons, which are not connected, may be driven by common synaptic inputs. Their outputs add together at the level of the motor neurons to produce effects that are greater than the sum of their individual effects. 5. It is proposed that graded interactions between these local interneurons are an essential element in the generation of motor patterns.", "contents": "Graded synaptic interactions between local premotor interneurons of the locust. 1. Graded synaptic interactions are revealed between pairs of nonspiking, local interneurons in the metathroracic ganglion of the locust. These interneurons drive motor neurons innervating muscles of a hindleg. 2. All the interactions found between the interneurons are inhibitory and one way. Synaptic transmission is effected by the graded release of chemical transmitter. Some of the connections are apparently direct. One local interneuron can, therefore, exert a graded control over the membrane potential of another local interneuron. 3. There are inhibitory connections between local interneurons that excite the same motor neuron, between local interneurons that excite antagonistic motor neurons, and between local interneurons that excite motor neurons to muscles moving different joints of a hindleg. 4. Other pairs of interneurons, which are not connected, may be driven by common synaptic inputs. Their outputs add together at the level of the motor neurons to produce effects that are greater than the sum of their individual effects. 5. It is proposed that graded interactions between these local interneurons are an essential element in the generation of motor patterns."}
{"id": "PMID:225449", "title": "Response properties and synaptic connections of mechanoafferent neurons in cerebral ganglion of Aplysia.", "content": "1. The cells of two clusters of small neurons on the ventrocaudal surface of each hemicerebral ganglion of Aplysia were found to exhibit action potentials following tactile stimuli applied to the skin of the head. These neurons appear to be mechanosensory afferents since they possess axons in the nerves innervating the skin and tactile stimulation evokes spikes with no prepotentials, even when the cell bodies are sufficiently hyperpolarized to block some spikes. The mechanosensory afferents may be primary afferents since the sensory response persists after chemical synaptic transmission is blocked by bathing the ganglion and peripheral structures in seawater with a high-Mg2+ and low-Ca2+ content. 2. The mechanosensory afferents are normally silent and are insensitive to photic, thermal, and chemical stimuli. A punctate tactile stimulus applied to a circumscribed region of skin can evoke a burst of spikes. If the stimulus is maintained at a constant forces, the mechanosensory response slowly adapts over a period of seconds. Repeated brief stimuli have little or no effect on spike frequency within a burst. 3. Approximately 81% of the mechanoafferent neurons have a single ipsilateral receptive field. The fields are located on the lips, the anterior tentacles, the dorsal portion of the head, the neck, or the perioral zone. Because many cells have collateral axons in the cerebral connectives, receptive fields elsewhere on the body are a possibility. The highest receptive-field density was associated with the lips. Within each area, receptive fields vary in size and shape. Adjacent fields overlap and larger fields frequently encompass several smaller ones. The features of some fields appear invariant from one animal to the next. A loose form of topographic organization of the mechanoafferent cells was observed. For example, cells located in the medial cluster have lip receptive fields, and most cells in the posterolateral portion of the lateral clusters have tentacle receptive fields. 4. Intracellular stimulation of individual mechanoafferents evokes short and constant-latency EPSPs in putative motor neurons comprising the identified B-cell clusters of the cerebral ganglion. On the basis of several criteria, these EPSPs appear to be several criteria, these EPSPs appear to be chemically mediated and are monosynaptic. 5. Repetitive intracellular stimulation of individual mechanoafferent neurons at low rates results in a gradual decrement in the amplitude of the EPSPs evoked in B cluster neurons. EPSP amplitude can be restored following brief periods of rest, but subsequent stimulation leads to further diminution of the response. 6. A decremented response cannot be restored by strong mechanical stimulation outside the receptive field of the mechanoafferent or by electrical stimulation of the cerebral nerves or connectives...", "contents": "Response properties and synaptic connections of mechanoafferent neurons in cerebral ganglion of Aplysia. 1. The cells of two clusters of small neurons on the ventrocaudal surface of each hemicerebral ganglion of Aplysia were found to exhibit action potentials following tactile stimuli applied to the skin of the head. These neurons appear to be mechanosensory afferents since they possess axons in the nerves innervating the skin and tactile stimulation evokes spikes with no prepotentials, even when the cell bodies are sufficiently hyperpolarized to block some spikes. The mechanosensory afferents may be primary afferents since the sensory response persists after chemical synaptic transmission is blocked by bathing the ganglion and peripheral structures in seawater with a high-Mg2+ and low-Ca2+ content. 2. The mechanosensory afferents are normally silent and are insensitive to photic, thermal, and chemical stimuli. A punctate tactile stimulus applied to a circumscribed region of skin can evoke a burst of spikes. If the stimulus is maintained at a constant forces, the mechanosensory response slowly adapts over a period of seconds. Repeated brief stimuli have little or no effect on spike frequency within a burst. 3. Approximately 81% of the mechanoafferent neurons have a single ipsilateral receptive field. The fields are located on the lips, the anterior tentacles, the dorsal portion of the head, the neck, or the perioral zone. Because many cells have collateral axons in the cerebral connectives, receptive fields elsewhere on the body are a possibility. The highest receptive-field density was associated with the lips. Within each area, receptive fields vary in size and shape. Adjacent fields overlap and larger fields frequently encompass several smaller ones. The features of some fields appear invariant from one animal to the next. A loose form of topographic organization of the mechanoafferent cells was observed. For example, cells located in the medial cluster have lip receptive fields, and most cells in the posterolateral portion of the lateral clusters have tentacle receptive fields. 4. Intracellular stimulation of individual mechanoafferents evokes short and constant-latency EPSPs in putative motor neurons comprising the identified B-cell clusters of the cerebral ganglion. On the basis of several criteria, these EPSPs appear to be several criteria, these EPSPs appear to be chemically mediated and are monosynaptic. 5. Repetitive intracellular stimulation of individual mechanoafferent neurons at low rates results in a gradual decrement in the amplitude of the EPSPs evoked in B cluster neurons. EPSP amplitude can be restored following brief periods of rest, but subsequent stimulation leads to further diminution of the response. 6. A decremented response cannot be restored by strong mechanical stimulation outside the receptive field of the mechanoafferent or by electrical stimulation of the cerebral nerves or connectives..."}
{"id": "PMID:225450", "title": "Spontaneous electrical activity and interaction of large and small cells in cardiac ganglion of the crab, Portunus sanguinolentus.", "content": "1. Semi-isolated preparations of the nine-celled cardiac ganglion of the crab, Portunus sanguinolentus, were studied electrophysiologically, using simultaneous recording from extracellular and two or three intracellular electrodes. Nine penetrations of small cells were achieved. 2. Three large (80 x 120 micron) cells lie near the anterior end of the 5-mm main trunk; two large and four small (less than 50 micron) cells at the posterior end. Large-cell axons pass along the main trunk and then exit to innervate cardiac muscle; small-cell axons do not leave the ganglion. 3. The semi-isolated ganglion produces spontaneous electrical activity organized into regularly patterned, rhythmic bursts of large- and small-cell impulses recurring at rates of 0.3-0.6/s and lasting 500-800 ms. Small impulse activity commences and ends each burst. Small cells fire trains during the burst, but impulses are not synchronized among them. Large-cell trains are synchronous, are at about one-half the frequency, and have fewer impulses than small-cell trains. 4. Intracellular recordings from small cells show a slow, pacemaker depolarization from a maximum membrane potential of -54 mV leading with only a slight inflection at ca. -50 mV to a depolarized plateau at ca. -40 mV; nonovershooting impulses are superimposed on this but cease before it repolarizes. Impulses, therefore, arise at a site distant from the soma and do not invade it. Deflections suggesting synaptic potentials are not seen. 5. Intracellular recordings from large cells show complex depolarizations corresponding to extracellularly recorded bursts. These represent excitatory postsynaptic potentials (EPSPs) corresponding with individual small-cell impulses, attenuated, non-overshooting spikes, and an underlying slow depolarization; usually no pacemaker depolarization is apparent between bursts. Chemically mediated transmission is probable for the EPSPs because they show delay, increase in amplitude with hyperpolarization, sometimes show facilitation, and are reduced in saline having one-third Ca, 3 x Mg. 6. EPSPs, impulses, and the slow depolarization occur synchronously among the large cells. Potentials recorded from posterior cells are attenuated and slower than those of the anterior cells. This is interpreted to reflect sites of occurrence more distant from the soma in the posterior than in the anterior cells. Impulses do not invade the somata. 7. Intracellular recordings from large-cell axons 4 mm from the soma show overshooting action potentials arising sharply from a base line. EPSPs are absent or highly attenuated and there is little underlying  depolarization (less than 2 mV). 8. Current passing with electrodes intracellular to two cells has established directly that all large cells are electrotonically coupled and that an anterior cell and a small cell are coupled. Changes of burst rate during current passing into any large cell indicate that all large cells and small cells are electrotonically coupled. 9...", "contents": "Spontaneous electrical activity and interaction of large and small cells in cardiac ganglion of the crab, Portunus sanguinolentus. 1. Semi-isolated preparations of the nine-celled cardiac ganglion of the crab, Portunus sanguinolentus, were studied electrophysiologically, using simultaneous recording from extracellular and two or three intracellular electrodes. Nine penetrations of small cells were achieved. 2. Three large (80 x 120 micron) cells lie near the anterior end of the 5-mm main trunk; two large and four small (less than 50 micron) cells at the posterior end. Large-cell axons pass along the main trunk and then exit to innervate cardiac muscle; small-cell axons do not leave the ganglion. 3. The semi-isolated ganglion produces spontaneous electrical activity organized into regularly patterned, rhythmic bursts of large- and small-cell impulses recurring at rates of 0.3-0.6/s and lasting 500-800 ms. Small impulse activity commences and ends each burst. Small cells fire trains during the burst, but impulses are not synchronized among them. Large-cell trains are synchronous, are at about one-half the frequency, and have fewer impulses than small-cell trains. 4. Intracellular recordings from small cells show a slow, pacemaker depolarization from a maximum membrane potential of -54 mV leading with only a slight inflection at ca. -50 mV to a depolarized plateau at ca. -40 mV; nonovershooting impulses are superimposed on this but cease before it repolarizes. Impulses, therefore, arise at a site distant from the soma and do not invade it. Deflections suggesting synaptic potentials are not seen. 5. Intracellular recordings from large cells show complex depolarizations corresponding to extracellularly recorded bursts. These represent excitatory postsynaptic potentials (EPSPs) corresponding with individual small-cell impulses, attenuated, non-overshooting spikes, and an underlying slow depolarization; usually no pacemaker depolarization is apparent between bursts. Chemically mediated transmission is probable for the EPSPs because they show delay, increase in amplitude with hyperpolarization, sometimes show facilitation, and are reduced in saline having one-third Ca, 3 x Mg. 6. EPSPs, impulses, and the slow depolarization occur synchronously among the large cells. Potentials recorded from posterior cells are attenuated and slower than those of the anterior cells. This is interpreted to reflect sites of occurrence more distant from the soma in the posterior than in the anterior cells. Impulses do not invade the somata. 7. Intracellular recordings from large-cell axons 4 mm from the soma show overshooting action potentials arising sharply from a base line. EPSPs are absent or highly attenuated and there is little underlying  depolarization (less than 2 mV). 8. Current passing with electrodes intracellular to two cells has established directly that all large cells are electrotonically coupled and that an anterior cell and a small cell are coupled. Changes of burst rate during current passing into any large cell indicate that all large cells and small cells are electrotonically coupled. 9..."}
{"id": "PMID:225457", "title": "Changes in activity of the Cu-Zn superoxide dismutase enzyme in tissues of the rat with changes in dietary copper.", "content": "The effects of dietary copper level on tissue activities of the copper containing superoxide dismutase (CuSOD) were investigated, and these activities related to those of other copper containing enzymes particularly cytochrome oxidase. Male weaning rats were fed a basal diet (containing 0.8 mg Cu/kg) or this diet supplemented with 4 or 24 mg Cu/kg. After 6 weeks, rats fed the basal diet were then repleted using the high copper diet. In the two copper supplemented groups, no differences were observed in any of the parameters measured. In these groups, tissue activities of CuSOD were in the order of liver greater than kidney greater than RBC greater than testis greater than heart greater than brain greater than lung greater than muscle. In the basal group, CuSOD activity decreased in liver; RBC and heart to 14, 25, and 61%, respectively, of control activities after 6 weeks' depletion; tissues other than brain or muscle showed smaller but significant changes. Conversely, heart and muscle cytochrome oxidase activities decreased to 30 and 45% of control activity and liver to 70%. With repletion, CuSOD activities in liver and heart increased more rapidly than did cytochrome oxidase activities. It is concluded that liver CuSOD activity, which is normally high, is greatly reduced with little change in cytochrome oxidase activity; the reverse is found for heart and muscle tissue. The relevance of these changes to the maintenance of tissue integrity is discussed.", "contents": "Changes in activity of the Cu-Zn superoxide dismutase enzyme in tissues of the rat with changes in dietary copper. The effects of dietary copper level on tissue activities of the copper containing superoxide dismutase (CuSOD) were investigated, and these activities related to those of other copper containing enzymes particularly cytochrome oxidase. Male weaning rats were fed a basal diet (containing 0.8 mg Cu/kg) or this diet supplemented with 4 or 24 mg Cu/kg. After 6 weeks, rats fed the basal diet were then repleted using the high copper diet. In the two copper supplemented groups, no differences were observed in any of the parameters measured. In these groups, tissue activities of CuSOD were in the order of liver greater than kidney greater than RBC greater than testis greater than heart greater than brain greater than lung greater than muscle. In the basal group, CuSOD activity decreased in liver; RBC and heart to 14, 25, and 61%, respectively, of control activities after 6 weeks' depletion; tissues other than brain or muscle showed smaller but significant changes. Conversely, heart and muscle cytochrome oxidase activities decreased to 30 and 45% of control activity and liver to 70%. With repletion, CuSOD activities in liver and heart increased more rapidly than did cytochrome oxidase activities. It is concluded that liver CuSOD activity, which is normally high, is greatly reduced with little change in cytochrome oxidase activity; the reverse is found for heart and muscle tissue. The relevance of these changes to the maintenance of tissue integrity is discussed."}
{"id": "PMID:225459", "title": "Identification of vitamin D3 and 7-dehydrocholesterol in cow's milk by gas chromatography-mass spectrometry and their quantitation by high-performance liquid chromatography.", "content": "Identification of vitamin D3 and 7-dehydrocholesterol (7-DHC) in cow's milk by gas chromatography-mass spectrometry (GC-MS) and their quantitation by high-performance liquid chromatography (HPLC) were investigated. When vitamin D and provitamin D fractions purified from a sample of commercial cow's milk were applied to GC-MS, the results showed that the fractions contained vitamin D3 and 7-DHC, respectively, while neither vitamin D2 nor ergosterol could be detected in the milk. HPLC methods for the determination of vitamin D3 and 7-DHC in cow's milk were then proposed as routine methods. The method for assaying vitamin D3 included the isolation of lipids from milk according to the directions of Bell and Christie (5), saponification, isolation of unsaponifiable matter, digitonin-Celite column chromatography, preparative thin-layer chromatography (TLC) and application to HPLC. On the other hand, 7-DHC in milk could be simultaneously determined without the purification by digitonin-Celite column chromatography. The peak corresponding to either vitamin D3 or 7-DHC in the respective HPL-chromatograms was clearly separated from possible interfering substances and the recovery experiments for both vitamin D3 and 7-DHC gave satisfactory results. When the proposed methods were applied to 10 samples of commercial cow's milk, the assayed values of vitamin D3 and 7-DHC were 19--79 I.U./liter and 14--56 microgram/liter, respectively.", "contents": "Identification of vitamin D3 and 7-dehydrocholesterol in cow's milk by gas chromatography-mass spectrometry and their quantitation by high-performance liquid chromatography. Identification of vitamin D3 and 7-dehydrocholesterol (7-DHC) in cow's milk by gas chromatography-mass spectrometry (GC-MS) and their quantitation by high-performance liquid chromatography (HPLC) were investigated. When vitamin D and provitamin D fractions purified from a sample of commercial cow's milk were applied to GC-MS, the results showed that the fractions contained vitamin D3 and 7-DHC, respectively, while neither vitamin D2 nor ergosterol could be detected in the milk. HPLC methods for the determination of vitamin D3 and 7-DHC in cow's milk were then proposed as routine methods. The method for assaying vitamin D3 included the isolation of lipids from milk according to the directions of Bell and Christie (5), saponification, isolation of unsaponifiable matter, digitonin-Celite column chromatography, preparative thin-layer chromatography (TLC) and application to HPLC. On the other hand, 7-DHC in milk could be simultaneously determined without the purification by digitonin-Celite column chromatography. The peak corresponding to either vitamin D3 or 7-DHC in the respective HPL-chromatograms was clearly separated from possible interfering substances and the recovery experiments for both vitamin D3 and 7-DHC gave satisfactory results. When the proposed methods were applied to 10 samples of commercial cow's milk, the assayed values of vitamin D3 and 7-DHC were 19--79 I.U./liter and 14--56 microgram/liter, respectively."}
{"id": "PMID:225460", "title": "Adenovirus type 21 bronchopneumonia in infants and young children.", "content": "An epidemic of bronchopneumonia in infants and young children, with adenovirus type 21 infection, was observed in Auckland, New Zealand, in 1977. Eighteen children, four to 44 months of age, with clinical and radiologic evidence of bronchopneumonia are described. Several of the children were seriously ill but there were no deaths. When reviewed six to 12 months after diagnosis, six children had clinical signs and 13 had radiologic signs of residual pulmonary disease. There were no detectable pulmonary sequelae in two children. Three children were lost to follow-up and could not be evaluated. Adenovirus type 21 bronchopneumonia is a serious illness and an important cause of chronic bronchopneumopathy in infants and young children.", "contents": "Adenovirus type 21 bronchopneumonia in infants and young children. An epidemic of bronchopneumonia in infants and young children, with adenovirus type 21 infection, was observed in Auckland, New Zealand, in 1977. Eighteen children, four to 44 months of age, with clinical and radiologic evidence of bronchopneumonia are described. Several of the children were seriously ill but there were no deaths. When reviewed six to 12 months after diagnosis, six children had clinical signs and 13 had radiologic signs of residual pulmonary disease. There were no detectable pulmonary sequelae in two children. Three children were lost to follow-up and could not be evaluated. Adenovirus type 21 bronchopneumonia is a serious illness and an important cause of chronic bronchopneumopathy in infants and young children."}
{"id": "PMID:225463", "title": "Multilocular cyst of the kidney.", "content": "Five cases of multilocular cyst of the kidney are presented with a follow-up of 8 mo to 13 yr. Two children were treated with partial nephrectomy and three with nephrectomy. Radiation therapy and chemotherapy were not given pre- or postoperatively. Ultrasonography is helpful in preoperative diagnosis of this lesion. A brief review of the literature, differential diagnosis, possible etiology, preoperative evaluation and treatment are discussed.", "contents": "Multilocular cyst of the kidney. Five cases of multilocular cyst of the kidney are presented with a follow-up of 8 mo to 13 yr. Two children were treated with partial nephrectomy and three with nephrectomy. Radiation therapy and chemotherapy were not given pre- or postoperatively. Ultrasonography is helpful in preoperative diagnosis of this lesion. A brief review of the literature, differential diagnosis, possible etiology, preoperative evaluation and treatment are discussed."}
{"id": "PMID:225464", "title": "Malignant presacral teratoma in children.", "content": "Malignant presacral teratoma is a rare tumor seen predominantly in young female children. The introduction of planned multidisciplinary treatment has improved the outlook for patients with this once dismal disease. Six female children were seen at Memorial Hospital with the diagnosis of malignant presacral teratoma. Five children were age 17 mo to 3 yr and the sixth child was 13 yr old at diagnosis. Presenting symptoms included masses in the buttock or groin, constipation, difficulty voiding, and local pain. Pathological features were varied and complex but three had predominantly endodermal sinus features. One child had the malignant presacral teratoma develop 18 mo after successful resection of a benign sacrosoccygeal teratoma in the newborn period. Treatment varied in the six cases since all were referred after failure of treatment elsewhere. All children had surgery, irradiation, and multiple drug chemotherapy. Four of the six children are surviving disease-free, 3 more than 24 mo off treatment. Evolution of treatment up to the present protocol management is discussed.", "contents": "Malignant presacral teratoma in children. Malignant presacral teratoma is a rare tumor seen predominantly in young female children. The introduction of planned multidisciplinary treatment has improved the outlook for patients with this once dismal disease. Six female children were seen at Memorial Hospital with the diagnosis of malignant presacral teratoma. Five children were age 17 mo to 3 yr and the sixth child was 13 yr old at diagnosis. Presenting symptoms included masses in the buttock or groin, constipation, difficulty voiding, and local pain. Pathological features were varied and complex but three had predominantly endodermal sinus features. One child had the malignant presacral teratoma develop 18 mo after successful resection of a benign sacrosoccygeal teratoma in the newborn period. Treatment varied in the six cases since all were referred after failure of treatment elsewhere. All children had surgery, irradiation, and multiple drug chemotherapy. Four of the six children are surviving disease-free, 3 more than 24 mo off treatment. Evolution of treatment up to the present protocol management is discussed."}
{"id": "PMID:225466", "title": "Conjugated estrogens bioinequivalence: comparison of four products in postmenopausal women.", "content": "The bioequivalence of four conjugated estrogens tablets USP was compared by measurement of seven estrogens or estrogen metabolites in the urine during steady-state dosing in postmenopausal women. Two studies compared three generic products with the innovator's product. The urinary excretion of 17 alpha-dihydroequilin, 17 alpha-dihydroequilenin, and 17 alpha-estradiol were significantly greater in all cases with the innovator's product than with the generic products. Statistically significant differences between products were observed occasionally for other components. The generic products thus were bioinequivalent to the innovator's product, although all products essentially met current compendial specifications. A third study observed no significant differences between three batches of the innovator's product for the seven components. Total conjugated estrogens excretion of all products at the steady state was essentially equal and correlated with neither disintegration time nor dissolution half-time. Bioinequivalence between products is discussed in relation to the need for an improved USP conjugated estrogens monograph. Evidence suggesting the metabolism of a fraction of dosed estrone, equilin, and 17 alpha-dihydroequilin to 17 beta-estradiol, 17 beta-dihydorequilim, and 17 alpha-dihydroequilenin, respectively, is presented.", "contents": "Conjugated estrogens bioinequivalence: comparison of four products in postmenopausal women. The bioequivalence of four conjugated estrogens tablets USP was compared by measurement of seven estrogens or estrogen metabolites in the urine during steady-state dosing in postmenopausal women. Two studies compared three generic products with the innovator's product. The urinary excretion of 17 alpha-dihydroequilin, 17 alpha-dihydroequilenin, and 17 alpha-estradiol were significantly greater in all cases with the innovator's product than with the generic products. Statistically significant differences between products were observed occasionally for other components. The generic products thus were bioinequivalent to the innovator's product, although all products essentially met current compendial specifications. A third study observed no significant differences between three batches of the innovator's product for the seven components. Total conjugated estrogens excretion of all products at the steady state was essentially equal and correlated with neither disintegration time nor dissolution half-time. Bioinequivalence between products is discussed in relation to the need for an improved USP conjugated estrogens monograph. Evidence suggesting the metabolism of a fraction of dosed estrone, equilin, and 17 alpha-dihydroequilin to 17 beta-estradiol, 17 beta-dihydorequilim, and 17 alpha-dihydroequilenin, respectively, is presented."}
{"id": "PMID:225467", "title": "Effect of cholera enterotoxin on pacemaker rate and cyclic adenosine 3':5'-monophosphate in isolated rabbit sinoatrial node.", "content": "The positive chronotropic effect of cholera enterotoxin on isolated rabbit sinoatrial (S-A) node was investigated. This toxin produced a time and dose-related increase in pacemaker rate and cyclic adenosine 3':5'-monophosphate (cyclic AMP) levels and shifted to the left the dose-response curves of norepinephrine on the pacemaker rate and cyclic AMP content in the S-A node. Thus, the sensitivity of the S-A node to norepinephrine was increased by the toxin. These effects of the toxin were not blocked by propranolol. There was a linear relation between the increases in pacemaker rate and cyclic AMP content after application of both the toxin and norepinephrine. However, the slope of the regression line relating pacemaker rate to cyclic AMP level differed with these two agents. These results suggest that cholera enterotoxin increases pacemaker rate with activation of the adenylate cyclase system in the S-A node, but the mechanism differs from that of norepinephrine.", "contents": "Effect of cholera enterotoxin on pacemaker rate and cyclic adenosine 3':5'-monophosphate in isolated rabbit sinoatrial node. The positive chronotropic effect of cholera enterotoxin on isolated rabbit sinoatrial (S-A) node was investigated. This toxin produced a time and dose-related increase in pacemaker rate and cyclic adenosine 3':5'-monophosphate (cyclic AMP) levels and shifted to the left the dose-response curves of norepinephrine on the pacemaker rate and cyclic AMP content in the S-A node. Thus, the sensitivity of the S-A node to norepinephrine was increased by the toxin. These effects of the toxin were not blocked by propranolol. There was a linear relation between the increases in pacemaker rate and cyclic AMP content after application of both the toxin and norepinephrine. However, the slope of the regression line relating pacemaker rate to cyclic AMP level differed with these two agents. These results suggest that cholera enterotoxin increases pacemaker rate with activation of the adenylate cyclase system in the S-A node, but the mechanism differs from that of norepinephrine."}
{"id": "PMID:225469", "title": "Cardiac inotropic beta adrenoceptors are fully active at low temperature.", "content": "The purpose of this study was to test the adrenoceptor interconversion hypothesis of Kunos and Nickerson (Brit. J. Pharmacol. 59: 603--614, 1977) which claims that lowering temperature from 31 to 17 degrees C converts inotropic beta adrenoceptors in rat atria to alpha adrenoceptors. If lowering temperature transforms the adrenoceptor from a beta type to an alpha type, one should expect that the sympathomimetic drug phenylephrine would be more potent at the low than at the high temperature, that the reverse would be true for the sympathomimetic drug isoproterenol, and that the blocking ability of the beta adrenoceptor blocking drug propranolol might be reduced and that of the alpha adrenoceptor blocking drug phentolamine increased by lowering temperature. This was not observed. It was impossible to obtain satisfactory inotropic effects at 17 degrees C and the calcium concentration in the incubation medium had to be reduced, which lowered contractility and permitted strong inotropic effects. At 17 degrees C the sympathomimetic drug effects were inhibited only by propranolol and not by phentolamine, and there was no evidence of \"adrenoceptor interconversion.\"", "contents": "Cardiac inotropic beta adrenoceptors are fully active at low temperature. The purpose of this study was to test the adrenoceptor interconversion hypothesis of Kunos and Nickerson (Brit. J. Pharmacol. 59: 603--614, 1977) which claims that lowering temperature from 31 to 17 degrees C converts inotropic beta adrenoceptors in rat atria to alpha adrenoceptors. If lowering temperature transforms the adrenoceptor from a beta type to an alpha type, one should expect that the sympathomimetic drug phenylephrine would be more potent at the low than at the high temperature, that the reverse would be true for the sympathomimetic drug isoproterenol, and that the blocking ability of the beta adrenoceptor blocking drug propranolol might be reduced and that of the alpha adrenoceptor blocking drug phentolamine increased by lowering temperature. This was not observed. It was impossible to obtain satisfactory inotropic effects at 17 degrees C and the calcium concentration in the incubation medium had to be reduced, which lowered contractility and permitted strong inotropic effects. At 17 degrees C the sympathomimetic drug effects were inhibited only by propranolol and not by phentolamine, and there was no evidence of \"adrenoceptor interconversion.\""}
{"id": "PMID:225471", "title": "The neuronal organization of the rat subfornical organ in vitro and a test of the osmo- and morphine-receptor hypotheses.", "content": "1. Extracellular action potentials (units) were recorded from rat subfornical organ explants in vitro in response to addition of angiotensin II (AII) or carbamyl-choline (carbachol) or serotonin (5-HT) to the superfusion solution. The frequency recorded was dose dependent over a wide range (AII, 0.05--5 nM; carbachol, 2.7--2700 nM; 5-HT, 1--100 nM). Appropriate antagonists, sarc1-ala2 angiotensin (saralasin) for AII, atropine sulphate for carbachol and methysergide maleate for 5-HT, blocked these excitations. The effects were reversible except for that of atropine. 2. Two populations of AII-excited units were found. A superficial population lying between 15 and 45 microns from the ependymal surface was blocked only by  saralasin and another population lying more than 55 microns below the ependymal surface could be blocked by atropine as well as saralasin. Carbachol-evoked units generally lay below 45 microns, and 5-HT-evoked units were scattered evenly over the subfornical organ. It is suggested that superficial AII-excited neurones have a cholinergic excitatory synapse with the deeper carbachol-excited neurones. 3. No evidence was found for the hypothesis that neurones of the subfornical organ are excited by morphine or by changes in extracellular osmotic pressure. 4. All types of drug-excited unit, both superficial (15--55 microns) and deep (below 55 microns), could be driven polysynaptically from the body or columns of the fornix. Units driven antidromically or antidromically and synaptically were almost all more than 55 microns from the surface. 5-HT-evoked units were driven antidromically only by stimulation of the columns of the fornix. AII- and carbachol-evoked units could be driven antidromically or antidromically and synaptically by stimulation of the body or the columns of the fornix. It is suggested that AII units driven antidromically are actually carbachol-sensitive neurones driven by the more superficial AII-sensitive cells. 5. A model of the neuronal organization of the subfornical organ is suggested in which AII-sensitive neurones lying superficially are excited by substances borne by blood or cerebrospinal fluid and synapse with deeper carbachol-sensitive neurones. The axons of these deep neurones pass out of the subfornical organ in the columns and body of the fornix. Afferent fibres from the body and columns of the fornix polysynaptically excite both superficial and deep neurones. A recurrent inhibitory circuit is suggested on the output path.", "contents": "The neuronal organization of the rat subfornical organ in vitro and a test of the osmo- and morphine-receptor hypotheses. 1. Extracellular action potentials (units) were recorded from rat subfornical organ explants in vitro in response to addition of angiotensin II (AII) or carbamyl-choline (carbachol) or serotonin (5-HT) to the superfusion solution. The frequency recorded was dose dependent over a wide range (AII, 0.05--5 nM; carbachol, 2.7--2700 nM; 5-HT, 1--100 nM). Appropriate antagonists, sarc1-ala2 angiotensin (saralasin) for AII, atropine sulphate for carbachol and methysergide maleate for 5-HT, blocked these excitations. The effects were reversible except for that of atropine. 2. Two populations of AII-excited units were found. A superficial population lying between 15 and 45 microns from the ependymal surface was blocked only by  saralasin and another population lying more than 55 microns below the ependymal surface could be blocked by atropine as well as saralasin. Carbachol-evoked units generally lay below 45 microns, and 5-HT-evoked units were scattered evenly over the subfornical organ. It is suggested that superficial AII-excited neurones have a cholinergic excitatory synapse with the deeper carbachol-excited neurones. 3. No evidence was found for the hypothesis that neurones of the subfornical organ are excited by morphine or by changes in extracellular osmotic pressure. 4. All types of drug-excited unit, both superficial (15--55 microns) and deep (below 55 microns), could be driven polysynaptically from the body or columns of the fornix. Units driven antidromically or antidromically and synaptically were almost all more than 55 microns from the surface. 5-HT-evoked units were driven antidromically only by stimulation of the columns of the fornix. AII- and carbachol-evoked units could be driven antidromically or antidromically and synaptically by stimulation of the body or the columns of the fornix. It is suggested that AII units driven antidromically are actually carbachol-sensitive neurones driven by the more superficial AII-sensitive cells. 5. A model of the neuronal organization of the subfornical organ is suggested in which AII-sensitive neurones lying superficially are excited by substances borne by blood or cerebrospinal fluid and synapse with deeper carbachol-sensitive neurones. The axons of these deep neurones pass out of the subfornical organ in the columns and body of the fornix. Afferent fibres from the body and columns of the fornix polysynaptically excite both superficial and deep neurones. A recurrent inhibitory circuit is suggested on the output path."}
{"id": "PMID:225472", "title": "Transmitter release: ruthenium red used to demonstrate a possible role of sialic acid containing substrates.", "content": "1. The possible function of sialic acid-containing substrates (SACS) in synaptic terminals of Aplysia was studied by intracellular injection of ruthenium red and of neuraminidase. 2. Ruthenium red, a dye known to have sialic acid as a molecular target, blocked transmission irreversibly in both cholinergic (buccal ganglion) and non-cholinergic (cerebral ganglion) synapses. 3. An intracellular site of action is likely because much less ruthenium red was necessary to block transmission when it was injected intracellularly than when it was presented by bath perfusion. 4. Ca2+ spikes recorded in the presence of tetrodotoxin or in Na+-free solution were not modified by ruthenium red or neuraminidase injections or perfusions. It is therefore improbable that these substances blocked transmission by blocking voltage-dependent Ca2+ influx. 5. Strong electrotonic depolarization of a pre-synaptic interneurone in the presence of 10(-4) M-tetrodotoxin caused a sustained post-synaptic response, which was abolished by ruthenium red. This result eliminates axonal conduction block as the principal mechanism of ruthenium red action. 6. Post-synaptic responses to ionophoretically applied acetylcholine (ACh) were not modified by bath perfusion of 2 x 10(-2) M-ruthenium red. 7. Biochemical analysis of pools of [3H]ACh was performed after injection of a precursor, [3H]acetate, into an identified interneurone. Ruthenium red appeared to increase significantly the 'free' (cytoplasmic) ACh pool without any change of 'bound' (vesicular) [3H]ACh-pool. 8. A model is proposed in which SACS act as intracellular Ca2+ receptors involved in transmitter release.", "contents": "Transmitter release: ruthenium red used to demonstrate a possible role of sialic acid containing substrates. 1. The possible function of sialic acid-containing substrates (SACS) in synaptic terminals of Aplysia was studied by intracellular injection of ruthenium red and of neuraminidase. 2. Ruthenium red, a dye known to have sialic acid as a molecular target, blocked transmission irreversibly in both cholinergic (buccal ganglion) and non-cholinergic (cerebral ganglion) synapses. 3. An intracellular site of action is likely because much less ruthenium red was necessary to block transmission when it was injected intracellularly than when it was presented by bath perfusion. 4. Ca2+ spikes recorded in the presence of tetrodotoxin or in Na+-free solution were not modified by ruthenium red or neuraminidase injections or perfusions. It is therefore improbable that these substances blocked transmission by blocking voltage-dependent Ca2+ influx. 5. Strong electrotonic depolarization of a pre-synaptic interneurone in the presence of 10(-4) M-tetrodotoxin caused a sustained post-synaptic response, which was abolished by ruthenium red. This result eliminates axonal conduction block as the principal mechanism of ruthenium red action. 6. Post-synaptic responses to ionophoretically applied acetylcholine (ACh) were not modified by bath perfusion of 2 x 10(-2) M-ruthenium red. 7. Biochemical analysis of pools of [3H]ACh was performed after injection of a precursor, [3H]acetate, into an identified interneurone. Ruthenium red appeared to increase significantly the 'free' (cytoplasmic) ACh pool without any change of 'bound' (vesicular) [3H]ACh-pool. 8. A model is proposed in which SACS act as intracellular Ca2+ receptors involved in transmitter release."}
{"id": "PMID:225473", "title": "Disuse enhances synaptic efficacy in spinal mononeurones.", "content": "1. Monosynaptic excitatory post-synaptic potentials (e.p.s.p.s) were recorded from triceps surae motoneurones in the cat following section or chronic conduction block of the medial gastrocnemius (m.g.) nerve with tetrodotoxin (TTX) or after daily stimulation of the sciatic nerve. 2. The mean maximum amplitudes of homonymous and heteronymous monosynaptic e.p.s.p.s evoked by stimulation of the mg. nerve were reduced significantly between 1 and 2 weeks after section of the muscle nerve. The mean amplitudes of monosynaptic e.p.s.p.s produced in the same motoneurones by afferent volleys from the intact synergists showed no significant alterations. 3. Reduction of the amplitude of monosynaptic e.p.s.p.s. evoked by the sectioned m.g. afferent volleys was not prevented by daily stimulation of the sciatic nerve. The chronic stimulation of the sciatic nerve did not increase the amplitude of monosynaptic e.p.s.p.s evoked by stimulation of the intact, lateral gastrocnemius (l.g.) or soleus nerve. 4. Chronic conduction block of the intact m.g. nerve with TTX cuffs for 2 weeks resulted in a significant increase in the homonymous e.p.s.p. amplitude. The amplitude of the heteronymous e.p.s.p.s evoked in the same m.g. motoneurones by stimulation of the intact l.g. or soleus nerve showed no significant changes. 5. It is concluded that decreased central synaptic transmission following section of the peripheral nerve is not due to elimination of impulse activity (disuse) of the sensory input and that prolonged disuse of the sensory fibres causes an increase, rather than a decrease, in central synaptic efficacy.", "contents": "Disuse enhances synaptic efficacy in spinal mononeurones. 1. Monosynaptic excitatory post-synaptic potentials (e.p.s.p.s) were recorded from triceps surae motoneurones in the cat following section or chronic conduction block of the medial gastrocnemius (m.g.) nerve with tetrodotoxin (TTX) or after daily stimulation of the sciatic nerve. 2. The mean maximum amplitudes of homonymous and heteronymous monosynaptic e.p.s.p.s evoked by stimulation of the mg. nerve were reduced significantly between 1 and 2 weeks after section of the muscle nerve. The mean amplitudes of monosynaptic e.p.s.p.s produced in the same motoneurones by afferent volleys from the intact synergists showed no significant alterations. 3. Reduction of the amplitude of monosynaptic e.p.s.p.s. evoked by the sectioned m.g. afferent volleys was not prevented by daily stimulation of the sciatic nerve. The chronic stimulation of the sciatic nerve did not increase the amplitude of monosynaptic e.p.s.p.s evoked by stimulation of the intact, lateral gastrocnemius (l.g.) or soleus nerve. 4. Chronic conduction block of the intact m.g. nerve with TTX cuffs for 2 weeks resulted in a significant increase in the homonymous e.p.s.p. amplitude. The amplitude of the heteronymous e.p.s.p.s evoked in the same m.g. motoneurones by stimulation of the intact l.g. or soleus nerve showed no significant changes. 5. It is concluded that decreased central synaptic transmission following section of the peripheral nerve is not due to elimination of impulse activity (disuse) of the sensory input and that prolonged disuse of the sensory fibres causes an increase, rather than a decrease, in central synaptic efficacy."}
{"id": "PMID:225475", "title": "Evidence of a neurotransmitter role for aspartate and gamma-aminobutyric acid in the rat olfactory cortex.", "content": "1. Using a cortical cup technique, the release of seven endogenous amino acids from the isolated rat olfactory cortex slice has been monitored.2. Electrical stimulation of the lateral olfactory tract at a frequency of 4 min(-1) was accompanied by a significant increase in the release of aspartate, GABA and taurine; the release of GABA and aspartate but not that of taurine was Ca(2+)-dependent.3. Chronic unilateral bulbectomy was accompanied by a specific, significant fall in the aspartate content of the olfactory cortex which reached a maximum 5 days after surgery and persisted for at least a further 5 days. Electrical stimulation of the lateral olfactory tract of such preparations did not release any of the amino acids under investigation.4. When slices from the unoperated side were exposed to solutions containing 25 mM-K+ or stimulated with electrodes placed directly on the cortex enclosed by the cup there was a Ca(2+)-dependent release of aspartate and GABA accompanied by a Ca(2+)-independent release of taurine. Following chronic bulbectomy, these procedures failed to evoke significant release of aspartate whereas the characteristics of GABA and taurine release were unaltered.5. It is concluded that aspartate may be the excitatory transmitter of some of the terminals of the lateral olfactory tract fibres and that GABA may be a transmitter at some inhibitory synapses of the rat olfactory cortex.", "contents": "Evidence of a neurotransmitter role for aspartate and gamma-aminobutyric acid in the rat olfactory cortex. 1. Using a cortical cup technique, the release of seven endogenous amino acids from the isolated rat olfactory cortex slice has been monitored.2. Electrical stimulation of the lateral olfactory tract at a frequency of 4 min(-1) was accompanied by a significant increase in the release of aspartate, GABA and taurine; the release of GABA and aspartate but not that of taurine was Ca(2+)-dependent.3. Chronic unilateral bulbectomy was accompanied by a specific, significant fall in the aspartate content of the olfactory cortex which reached a maximum 5 days after surgery and persisted for at least a further 5 days. Electrical stimulation of the lateral olfactory tract of such preparations did not release any of the amino acids under investigation.4. When slices from the unoperated side were exposed to solutions containing 25 mM-K+ or stimulated with electrodes placed directly on the cortex enclosed by the cup there was a Ca(2+)-dependent release of aspartate and GABA accompanied by a Ca(2+)-independent release of taurine. Following chronic bulbectomy, these procedures failed to evoke significant release of aspartate whereas the characteristics of GABA and taurine release were unaltered.5. It is concluded that aspartate may be the excitatory transmitter of some of the terminals of the lateral olfactory tract fibres and that GABA may be a transmitter at some inhibitory synapses of the rat olfactory cortex."}
{"id": "PMID:225478", "title": "Electrical coupling between cones in turtle retina.", "content": "1. The electrical coupling between cones of known spectral sensitivity in the peripheral part of the turtle's retina was studied by passing current through a micro-electrode inserted into one cone and recording with a second micro-electrode inserted into a neighbouring cone. 2. Spatial sensitivity profiles were determined by recording flash responses to a long narrow strip of light which was moved across the impaled cones in orthogonal directions. These measurements gave both the length constant lambda of electrical spread in the cone network and the separation of the two cones. 3. The cone separation determined from the spatial profiles agreed closely with that measured directly by injecting a fluorescent dye into two cones. 4. The length constant lambda varied from 18 to 39 micron with a mean of 25 micron for red-sensitive cones and 26 micron for green-sensitive cones. 5. The majority of cone pairs studied were electrically coupled provided they had the same spectral sensitivity and were separated by less than 60 micron: thirty-two out of thirty-six red-red pairs, two out of two green-green pairs, none out of eight red-green pairs: no blue cones were observed. 6. The strength of electrical coupling was expressed as a mutual resistance defined as the voltage in one cell divided by the current flowing into the other. Mutual resistances decreased from a maximum value of about 30 M omega at separations close to zero to 0.2 M omega, the lower limit of detectable coupling at separations of about 60 micron. Mutual resistances were always positive and were independent of which cell was directly polarized. The coupling seemed to be ohmic and any rectification or non-linearity probably arose in the cone membranes rather than in the coupling resistances. 7. The results were analysed in terms of the Lamb & Simon (1977) theories of square and hexagonal lattices, which approximate to the continuous sheet model except in the case of the cone to which current is applied. 8. The total membrane resistance of a single cone was estimated as 100--300 M omega and the connecting resistances as 100 M omega for a square array and 170 M omega for a hexagonal array. The input resistance of a cone in the network was 25--50 M omega. Lower values were often obtained but may be due to injury by the micro-electrodes. 9. The time constant of an isolated cone was estimated as about 20 msec and the capacity as about 100 pF. 10. Discrepancies between experimental findings and theoretical predictions of the hexagonal or square array models were tentatively attributed to an overestimate of lambda resulting from light scattering.", "contents": "Electrical coupling between cones in turtle retina. 1. The electrical coupling between cones of known spectral sensitivity in the peripheral part of the turtle's retina was studied by passing current through a micro-electrode inserted into one cone and recording with a second micro-electrode inserted into a neighbouring cone. 2. Spatial sensitivity profiles were determined by recording flash responses to a long narrow strip of light which was moved across the impaled cones in orthogonal directions. These measurements gave both the length constant lambda of electrical spread in the cone network and the separation of the two cones. 3. The cone separation determined from the spatial profiles agreed closely with that measured directly by injecting a fluorescent dye into two cones. 4. The length constant lambda varied from 18 to 39 micron with a mean of 25 micron for red-sensitive cones and 26 micron for green-sensitive cones. 5. The majority of cone pairs studied were electrically coupled provided they had the same spectral sensitivity and were separated by less than 60 micron: thirty-two out of thirty-six red-red pairs, two out of two green-green pairs, none out of eight red-green pairs: no blue cones were observed. 6. The strength of electrical coupling was expressed as a mutual resistance defined as the voltage in one cell divided by the current flowing into the other. Mutual resistances decreased from a maximum value of about 30 M omega at separations close to zero to 0.2 M omega, the lower limit of detectable coupling at separations of about 60 micron. Mutual resistances were always positive and were independent of which cell was directly polarized. The coupling seemed to be ohmic and any rectification or non-linearity probably arose in the cone membranes rather than in the coupling resistances. 7. The results were analysed in terms of the Lamb & Simon (1977) theories of square and hexagonal lattices, which approximate to the continuous sheet model except in the case of the cone to which current is applied. 8. The total membrane resistance of a single cone was estimated as 100--300 M omega and the connecting resistances as 100 M omega for a square array and 170 M omega for a hexagonal array. The input resistance of a cone in the network was 25--50 M omega. Lower values were often obtained but may be due to injury by the micro-electrodes. 9. The time constant of an isolated cone was estimated as about 20 msec and the capacity as about 100 pF. 10. Discrepancies between experimental findings and theoretical predictions of the hexagonal or square array models were tentatively attributed to an overestimate of lambda resulting from light scattering."}
{"id": "PMID:225490", "title": "Respiratory chain components of Leishmania tropica promastigotes.", "content": "Crude preparations of kinetoplast vesicles were used to investigate the respiratory chain components in Leishmania tropica promastigotes. In difference spectra from enzymically and chemically reduced preparations, cytochrome b was the predominant component. By utilizing special assays designed to minimize the influence of cytochrome b on difference spectra, cytochromes a, a3 and c555 were demonstrated. Difference spectra from chemically reduced preparations indicated that pyridine nucleotides (NADH) and flavoproteins were also part of the respiratory chain. The presence of these components as well as their response to respiratory inhibitors and ascorbate provide evidence for the presence of a typical trypanosomatid respiratory chain in L. tropica promastigotes.", "contents": "Respiratory chain components of Leishmania tropica promastigotes. Crude preparations of kinetoplast vesicles were used to investigate the respiratory chain components in Leishmania tropica promastigotes. In difference spectra from enzymically and chemically reduced preparations, cytochrome b was the predominant component. By utilizing special assays designed to minimize the influence of cytochrome b on difference spectra, cytochromes a, a3 and c555 were demonstrated. Difference spectra from chemically reduced preparations indicated that pyridine nucleotides (NADH) and flavoproteins were also part of the respiratory chain. The presence of these components as well as their response to respiratory inhibitors and ascorbate provide evidence for the presence of a typical trypanosomatid respiratory chain in L. tropica promastigotes."}
{"id": "PMID:225492", "title": "Mechanism of liquefaction of the human ejaculate. II. Role of collagenase-like peptidase and seminal proteinase.", "content": "Collagenase-like peptidase and seminal proteinase were isolated from human testis and human seminal plasma. The effects of both enzymes upon proteins isolated from the human ejaculate were studied. Both enzymes degraded ejaculate proteins. The data suggest that collagenase-like peptidase is responsible for the first, and seminal proteinase for the second, phase of human ejaculate liquefaction in vitro.", "contents": "Mechanism of liquefaction of the human ejaculate. II. Role of collagenase-like peptidase and seminal proteinase. Collagenase-like peptidase and seminal proteinase were isolated from human testis and human seminal plasma. The effects of both enzymes upon proteins isolated from the human ejaculate were studied. Both enzymes degraded ejaculate proteins. The data suggest that collagenase-like peptidase is responsible for the first, and seminal proteinase for the second, phase of human ejaculate liquefaction in vitro."}
{"id": "PMID:225493", "title": "Starfish and horseshoe crab egg factors cause elevations of cyclic nucleotide concentrations in spermatozoa from starfish and horseshoe crabs.", "content": "Factors collected from the eggs of the starfish (Pisaster giganteus) and the horsehoe crab (Limulus polyphemus) caused significant increases in the sperm cyclic nucleotide concentrations of the respective species. Sea urchin egg factors, at concentrations that resulted in maximal cyclic nucleotide elevations in sea urchin spermatozoa, had no effect on those of starfish or horseshoe crab, suggesting a species specificity with respect to egg factor-induced changes in sperm cyclic nucleotide metabolism.", "contents": "Starfish and horseshoe crab egg factors cause elevations of cyclic nucleotide concentrations in spermatozoa from starfish and horseshoe crabs. Factors collected from the eggs of the starfish (Pisaster giganteus) and the horsehoe crab (Limulus polyphemus) caused significant increases in the sperm cyclic nucleotide concentrations of the respective species. Sea urchin egg factors, at concentrations that resulted in maximal cyclic nucleotide elevations in sea urchin spermatozoa, had no effect on those of starfish or horseshoe crab, suggesting a species specificity with respect to egg factor-induced changes in sperm cyclic nucleotide metabolism."}
{"id": "PMID:225494", "title": "The interaction of alpha-chlorohydrin with glycerol kinase.", "content": "alpha-Chlorohydrin has been examined both for its ability to act as a substrate for glycerol kinase and as an inhibitor of the reaction of glycerol with glycerol kinase. Using a purified enzyme from Candida mycoderma, it was established that alpha-chlorohydrin does not act as a substrate for glycerol kinase, but does act as a competitive inhibitor (Ki of 30 mM) of purified glycerol kinase and the enzyme present in a sonicated preparation of ram spermatozoa. Neither alpha-chlorohydrin nor alpha-chlorohydrin phosphate acted as inhibitors of NAD- or flavin-linked glycerolphosphate dehydrogenase. It is concluded that alpha-chlorohydrin does not cause the impairment of sperm metabolism as a result of phosphorylation catalysed by glycerol kinase.", "contents": "The interaction of alpha-chlorohydrin with glycerol kinase. alpha-Chlorohydrin has been examined both for its ability to act as a substrate for glycerol kinase and as an inhibitor of the reaction of glycerol with glycerol kinase. Using a purified enzyme from Candida mycoderma, it was established that alpha-chlorohydrin does not act as a substrate for glycerol kinase, but does act as a competitive inhibitor (Ki of 30 mM) of purified glycerol kinase and the enzyme present in a sonicated preparation of ram spermatozoa. Neither alpha-chlorohydrin nor alpha-chlorohydrin phosphate acted as inhibitors of NAD- or flavin-linked glycerolphosphate dehydrogenase. It is concluded that alpha-chlorohydrin does not cause the impairment of sperm metabolism as a result of phosphorylation catalysed by glycerol kinase."}
{"id": "PMID:225496", "title": "The binding of FSH, LH and PMSG to equine gonadal tissues.", "content": "Gonadotrophin-receptor binding studies involving the use of 125I-labelled highly purified FSH and LH have shown that equine gonadal tissues possess similar numbers of specific FSH and LH receptors per cell as the gonadal tissues of other mammals. However, while rat, cow and pig gonadal tissues were shown to bind as much 125I-labelled PMSG as 125I-labelled LH on a molar basis, the equivalent equine tissues bound only less than or equal to 4% as much of the labelled PMSG as LH. Competitive binding studies involving the use of radioreceptor assay techniques have further demonstrated that the small but significant degree of PMSG binding which does take place to equine tissues occurs at LH receptors and not at receptors specific for PMSG. The binding of PMSG to equine FSH receptors was negligible. These results suggest that PMSG (1) binds to equine LH receptors with about one-tenth the affinity of that observed with LH receptors of other species and (2) does not appear to bind specifically to equine FSH receptors. This would possibly explain the apparent refractoriness of mares' ovaries to exogenous and endogenous OMSG.", "contents": "The binding of FSH, LH and PMSG to equine gonadal tissues. Gonadotrophin-receptor binding studies involving the use of 125I-labelled highly purified FSH and LH have shown that equine gonadal tissues possess similar numbers of specific FSH and LH receptors per cell as the gonadal tissues of other mammals. However, while rat, cow and pig gonadal tissues were shown to bind as much 125I-labelled PMSG as 125I-labelled LH on a molar basis, the equivalent equine tissues bound only less than or equal to 4% as much of the labelled PMSG as LH. Competitive binding studies involving the use of radioreceptor assay techniques have further demonstrated that the small but significant degree of PMSG binding which does take place to equine tissues occurs at LH receptors and not at receptors specific for PMSG. The binding of PMSG to equine FSH receptors was negligible. These results suggest that PMSG (1) binds to equine LH receptors with about one-tenth the affinity of that observed with LH receptors of other species and (2) does not appear to bind specifically to equine FSH receptors. This would possibly explain the apparent refractoriness of mares' ovaries to exogenous and endogenous OMSG."}
{"id": "PMID:225497", "title": "Immunity to equine herpesvirus 1 infection in foals during the first year of life.", "content": "A band of 23 pregnant mares on a Thoroughbred breeding farm all had serum virus-neutralizing antibody titres to equine herpesvirus 1 (EHV-1). Antibody was not transferred to their foals in utero. All foals received antibody from colostrum and developed antibody titres similar to their dams. The serum virus-neutralizing antibody titres were observed in 10 of these foals for 1 year. Decay of passive immunity occurred at the rate of 3.25 two-fold dilutions in 100 days and reached zero at the mean time of 180 days. The foals were exposed to EHV-1 twice. Foals with a geometric mean titre of 1 : 25 experienced infection and a rise of titre, while those with a geometric mean titre of 1 : 76 resisted infection.", "contents": "Immunity to equine herpesvirus 1 infection in foals during the first year of life. A band of 23 pregnant mares on a Thoroughbred breeding farm all had serum virus-neutralizing antibody titres to equine herpesvirus 1 (EHV-1). Antibody was not transferred to their foals in utero. All foals received antibody from colostrum and developed antibody titres similar to their dams. The serum virus-neutralizing antibody titres were observed in 10 of these foals for 1 year. Decay of passive immunity occurred at the rate of 3.25 two-fold dilutions in 100 days and reached zero at the mean time of 180 days. The foals were exposed to EHV-1 twice. Foals with a geometric mean titre of 1 : 25 experienced infection and a rise of titre, while those with a geometric mean titre of 1 : 76 resisted infection."}
{"id": "PMID:225499", "title": "A general approach to proving the minimality of phylogenetic trees illustrated by an example with a set of 23 vertebrates.", "content": "We have recently described a method of building phylogenetic trees and have outlined an approach for proving whether a particular tree is optimal for the data used. In this paper we describe in detail the method of establishing lower bounds on the length of a minimal tree by partitioning the data set into subsets. All characters that could be involved in duplications in the data are paired with all other such characters. A matching algorithm is then used to obtain the pairing of characters that reveals the most duplications in the data. This matching may still not account for all nucleotide substitutions on the tree. The structure of the tree is then used to help select subsets of three or more characters until the lower bound found by partitioning is equal to the length of the tree. The tree must then be a minimal tree since no tree can exist with a length less than that of the lower bound. The method is demonstrated using a set of 23 vertebrate cytochrome c sequences with the criterion of minimizing the total number of nucleotide substitutions. There are 131130 7045768798 96033440625 topologically distinct trees that can be constructed from this data set. The method described in this paper does identify 144 minimal tree variants. The method is general in the sense that it can be used for other data and other criteria of length. It need not however always be possible to prove a treee minimal but the method will give an upper and lower bound on the length of minimal trees.", "contents": "A general approach to proving the minimality of phylogenetic trees illustrated by an example with a set of 23 vertebrates. We have recently described a method of building phylogenetic trees and have outlined an approach for proving whether a particular tree is optimal for the data used. In this paper we describe in detail the method of establishing lower bounds on the length of a minimal tree by partitioning the data set into subsets. All characters that could be involved in duplications in the data are paired with all other such characters. A matching algorithm is then used to obtain the pairing of characters that reveals the most duplications in the data. This matching may still not account for all nucleotide substitutions on the tree. The structure of the tree is then used to help select subsets of three or more characters until the lower bound found by partitioning is equal to the length of the tree. The tree must then be a minimal tree since no tree can exist with a length less than that of the lower bound. The method is demonstrated using a set of 23 vertebrate cytochrome c sequences with the criterion of minimizing the total number of nucleotide substitutions. There are 131130 7045768798 96033440625 topologically distinct trees that can be constructed from this data set. The method described in this paper does identify 144 minimal tree variants. The method is general in the sense that it can be used for other data and other criteria of length. It need not however always be possible to prove a treee minimal but the method will give an upper and lower bound on the length of minimal trees."}
{"id": "PMID:225501", "title": "Mouse mammary tumor virus infections: viral expression and tumor risk.", "content": "Concentrations of murine mammary tumor virus (MuMTV) antigen in the milk of individual naturally infected BALB/cfC3H and BALB/c mice given injections of MuMTV were related to their risk of developing a mammary tumor. Two distinct groups of MuMTV-infected mice were identified. One group exhibited high viral antigen levels in their milk (greater than or equal to 100 micrograms/ml), whereas the other group exhibited low viral antigen levels in their milk (less than or equal to 3 micrograms/ml). Mice that exhibited high levels developed tumors by 17 months of age, whereas those with low levels did not. Viral expression levels in mice having high risks of tumor development were also related to the length of the latency period preceding overt tumor development. The tumor risk potential of naturally infected mice was frequently that of their mothers. Various doses of MuMTV were injected into BALB/c mice, and the resulting infections differed in latency period, level of viral expression, and potential for neoplastic transformation.", "contents": "Mouse mammary tumor virus infections: viral expression and tumor risk. Concentrations of murine mammary tumor virus (MuMTV) antigen in the milk of individual naturally infected BALB/cfC3H and BALB/c mice given injections of MuMTV were related to their risk of developing a mammary tumor. Two distinct groups of MuMTV-infected mice were identified. One group exhibited high viral antigen levels in their milk (greater than or equal to 100 micrograms/ml), whereas the other group exhibited low viral antigen levels in their milk (less than or equal to 3 micrograms/ml). Mice that exhibited high levels developed tumors by 17 months of age, whereas those with low levels did not. Viral expression levels in mice having high risks of tumor development were also related to the length of the latency period preceding overt tumor development. The tumor risk potential of naturally infected mice was frequently that of their mothers. Various doses of MuMTV were injected into BALB/c mice, and the resulting infections differed in latency period, level of viral expression, and potential for neoplastic transformation."}
{"id": "PMID:225502", "title": "Human serum and the growth of human mammary cells.", "content": "Human serum from a pool of normal donors, in the presence of fetal bovine serum, inhibited the growth of the major epithelial cell type observed in primary cultures established from biopsy samples of breast carcinoma. In contrast, the growth of cells from nonmalignant mammary tissues removed during reduction mammoplasty and from fibroadenoma was not inhibited. The replication of MCF-7 cells, an established line from a metastatic breast lesion, was also inhibited, whereas the growth of HBL-100 cells, originally derived from a presumably normal source of mammary tissue, was not inhibited by human serum in combination with fetal bovine serum. The growth of two additional cell lines, MDA 157 and MDA 231, was also not affected by human serum. Studies of growth in primary cultures were restricted primarily to direct microscopic observations of the number of cells per colony and the proportion labeled with [3H]thymidine. The results indicate the use of cell lines as adjuncts to primary cultures in future studies of this inhibitory activity.", "contents": "Human serum and the growth of human mammary cells. Human serum from a pool of normal donors, in the presence of fetal bovine serum, inhibited the growth of the major epithelial cell type observed in primary cultures established from biopsy samples of breast carcinoma. In contrast, the growth of cells from nonmalignant mammary tissues removed during reduction mammoplasty and from fibroadenoma was not inhibited. The replication of MCF-7 cells, an established line from a metastatic breast lesion, was also inhibited, whereas the growth of HBL-100 cells, originally derived from a presumably normal source of mammary tissue, was not inhibited by human serum in combination with fetal bovine serum. The growth of two additional cell lines, MDA 157 and MDA 231, was also not affected by human serum. Studies of growth in primary cultures were restricted primarily to direct microscopic observations of the number of cells per colony and the proportion labeled with [3H]thymidine. The results indicate the use of cell lines as adjuncts to primary cultures in future studies of this inhibitory activity."}
{"id": "PMID:225503", "title": "Sarcomas induced by injection of simian virus 40 into neonatal CFW mice.", "content": "Sarcomas were induced in CFW mice by the iv inoculation of simian virus 40 (SV40) in neonatal animals. Infection with murine malaria parasites, Plasmodium berghei yoelli, decreased the latency and increased the incidence and invasiveness of the tumors. All mice given both SV40 and P. berghei yoelli had sarcomas of the liver and spleen at 9 months of age. At 11 months of age, 70% of the SV40-inoculated mice had sarcomas of the liver indistinguishable from those in the group given both pathogens. Only 1 lung metastasis was seen in the SV40-treated group. The sarcomas contained SV40 T-antigen as revealed by the indirect immunofluorescence technique. Among adult CFW mice given iv injections of SV40, only 2 tumors were found at 11 or 12 months after virus inoculation. Both tumors were in the lungs; 1 was an adenoma and 1 was a papillary adenocarcinoma. Neither gave a positive reaction with the immunofluorescence test.", "contents": "Sarcomas induced by injection of simian virus 40 into neonatal CFW mice. Sarcomas were induced in CFW mice by the iv inoculation of simian virus 40 (SV40) in neonatal animals. Infection with murine malaria parasites, Plasmodium berghei yoelli, decreased the latency and increased the incidence and invasiveness of the tumors. All mice given both SV40 and P. berghei yoelli had sarcomas of the liver and spleen at 9 months of age. At 11 months of age, 70% of the SV40-inoculated mice had sarcomas of the liver indistinguishable from those in the group given both pathogens. Only 1 lung metastasis was seen in the SV40-treated group. The sarcomas contained SV40 T-antigen as revealed by the indirect immunofluorescence technique. Among adult CFW mice given iv injections of SV40, only 2 tumors were found at 11 or 12 months after virus inoculation. Both tumors were in the lungs; 1 was an adenoma and 1 was a papillary adenocarcinoma. Neither gave a positive reaction with the immunofluorescence test."}
{"id": "PMID:225504", "title": "Squirrel monkey retrovirus and Herpesvirus saimiri: observation in the same cell following isolation.", "content": "Electron microscopic examination of mink lung cells previously cultured with a squirrel monkey (Saimiri sciureus) throat swab suspension revealed the presence of squirrel monkey retrovirus (SMRV) and Herpesvirus saimiri (HVS) coexisting within the same cells in culture. HVS was identified by serum neutralization, and the retrovirus isolate was identified as SMRV by a morphologic examination, microimmunodiffusion analysis, and demonstration of an Mg2+ preference for the RNA-directed DNA polymerase.", "contents": "Squirrel monkey retrovirus and Herpesvirus saimiri: observation in the same cell following isolation. Electron microscopic examination of mink lung cells previously cultured with a squirrel monkey (Saimiri sciureus) throat swab suspension revealed the presence of squirrel monkey retrovirus (SMRV) and Herpesvirus saimiri (HVS) coexisting within the same cells in culture. HVS was identified by serum neutralization, and the retrovirus isolate was identified as SMRV by a morphologic examination, microimmunodiffusion analysis, and demonstration of an Mg2+ preference for the RNA-directed DNA polymerase."}
{"id": "PMID:225505", "title": "Failure to confirm evidence for a nonvirion tumor-specific surface antigen in avian retrovirus-transformed cells.", "content": "Triton X-100 or Nonidet P40-deoxycholate extracts of [3H]fucose-labeled Rous sarcoma virus-transformed chick embryo fibroblasts were examined by indirect immunoprecipitation for the presence of a tumor-specific neoantigen of 100,000 daltons. Extracts were incubated with immune IgG from Rous tumor-sensitized chickens, and the resultant antigen-antibody complexes were precipitated with rabbit antichicken IgG and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Radioactivity appeared between the migration positions of proteins having molecular weights of 65,000 and 95,000 daltons and at about 30,000 daltons. These antigens were group-specific, and thei precipitation could be inhibited by competition with extracts from cultured fibroblasts that had been infected with a nontransforming avian leukosis virus. They were not precipitated with IgG from unimmunized chickens or chickens immunized with the culture supernatants of uninfected chick embryo fibroblasts. In contrast to results reported recently, the present results could not confirm by immunoprecipitation, the existence of a tumor neoantigen different from that associated with viral components. However, the tumor-specific antigen possibly existed on the cell surface but was not preserved in these detergent extracts.", "contents": "Failure to confirm evidence for a nonvirion tumor-specific surface antigen in avian retrovirus-transformed cells. Triton X-100 or Nonidet P40-deoxycholate extracts of [3H]fucose-labeled Rous sarcoma virus-transformed chick embryo fibroblasts were examined by indirect immunoprecipitation for the presence of a tumor-specific neoantigen of 100,000 daltons. Extracts were incubated with immune IgG from Rous tumor-sensitized chickens, and the resultant antigen-antibody complexes were precipitated with rabbit antichicken IgG and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Radioactivity appeared between the migration positions of proteins having molecular weights of 65,000 and 95,000 daltons and at about 30,000 daltons. These antigens were group-specific, and thei precipitation could be inhibited by competition with extracts from cultured fibroblasts that had been infected with a nontransforming avian leukosis virus. They were not precipitated with IgG from unimmunized chickens or chickens immunized with the culture supernatants of uninfected chick embryo fibroblasts. In contrast to results reported recently, the present results could not confirm by immunoprecipitation, the existence of a tumor neoantigen different from that associated with viral components. However, the tumor-specific antigen possibly existed on the cell surface but was not preserved in these detergent extracts."}
{"id": "PMID:225506", "title": "Epidemiological study of carcinoma of liver in Dodoma region in Tanzania.", "content": "Primary hepatocellular carcinoma is a common disease in Africa, particularly in Mozambique, South Africa, Zambia, Kenya, etc. In Dodoma Region of Tanzania, the populace consumes large numbers of ground nuts which are believed to predispose to liver cancer. Of 939 clinically diagnosed malignancies in the Region during 1972-1976, 256 (27 percent) were primary hepatocellular carcinomas. An analysis of these findings is presented.", "contents": "Epidemiological study of carcinoma of liver in Dodoma region in Tanzania. Primary hepatocellular carcinoma is a common disease in Africa, particularly in Mozambique, South Africa, Zambia, Kenya, etc. In Dodoma Region of Tanzania, the populace consumes large numbers of ground nuts which are believed to predispose to liver cancer. Of 939 clinically diagnosed malignancies in the Region during 1972-1976, 256 (27 percent) were primary hepatocellular carcinomas. An analysis of these findings is presented."}
{"id": "PMID:225509", "title": "RNase III cleaves vesicular stomatitis virus genome-length RNAs but fails to cleave viral mRNA's.", "content": "The procaryotic RNA processing enzyme RNase III (endoribonuclease III [EC 3.1.4.24]) was used to probe vesicular stomatitis virus (VSV) RNAs for specific sites that could be recognized and cleaved. The effect of the enzyme on the RNAs was monitored by measuring their subsequent migration in denaturing agarose-urea gels. VSV virion RNA (negative strand; Mr, 4 X 10(6)) was cleaved by the enzyme to yield a set of discrete fragments which ranged on size from 3.5 X 10(6) to 0.2 X 10(6) daltons. The cleavage was a function of enzyme concentration, salt concentration, and time. A maximum of 20 to 22 fragments was generated under conditions of low enzyme concentration or short times of incubation. VSV genome-length intracellular RNA of both + and - polarity was also cleaved by RNase III. In contrast to the findings with virion-length RNA, however, the migration rates of VSV mRNA's purified by chromatography on polyuridylic acid-Sepharose were unaffected by treatment with RNase III. These results show that specific sites in the virion RNA and its full-length complement can be recognized by RNase III. Sites of this type are not present in the polyadenylic acid-containing mRNA, however.", "contents": "RNase III cleaves vesicular stomatitis virus genome-length RNAs but fails to cleave viral mRNA's. The procaryotic RNA processing enzyme RNase III (endoribonuclease III [EC 3.1.4.24]) was used to probe vesicular stomatitis virus (VSV) RNAs for specific sites that could be recognized and cleaved. The effect of the enzyme on the RNAs was monitored by measuring their subsequent migration in denaturing agarose-urea gels. VSV virion RNA (negative strand; Mr, 4 X 10(6)) was cleaved by the enzyme to yield a set of discrete fragments which ranged on size from 3.5 X 10(6) to 0.2 X 10(6) daltons. The cleavage was a function of enzyme concentration, salt concentration, and time. A maximum of 20 to 22 fragments was generated under conditions of low enzyme concentration or short times of incubation. VSV genome-length intracellular RNA of both + and - polarity was also cleaved by RNase III. In contrast to the findings with virion-length RNA, however, the migration rates of VSV mRNA's purified by chromatography on polyuridylic acid-Sepharose were unaffected by treatment with RNase III. These results show that specific sites in the virion RNA and its full-length complement can be recognized by RNase III. Sites of this type are not present in the polyadenylic acid-containing mRNA, however."}
{"id": "PMID:225510", "title": "Assignment of the large oligonucleotides of vesicular stomatitis virus to the N, NS, M, G, and L genes and oligonucleotide gene ordering within the L gene.", "content": "Analyses of prototype vesicular stomatitis (VSV, Indiana serotype) mRNA-32P-labeled viral RNA duplexes have established the assignments of 65 of the 72 large oligonucleotides that are recovered by two-dimensional electrophoresis of RNase T1 digests of the viral RNA. Fifty of the oligonucleotides are recovered in the L RNA duplex, four each in the N, M, and NS duplexes, and three in the G RNA duplex. Studies of three small defective-particle RNA species indicate that they have only L gene oligonucleotides in addition to three of the seven unassigned oligonucleotides. Some L gene ordering of oligonucleotides can be postulated from the defective-particle RNA sequence analyses. Analyses of naturally occurring alternate isolates of VSV Indiana have established that by comparison to the prototype virus strain, the alternate isolates minimally have genome sequence differences in L, G, N, NS and/or unassigned regions of the genome. Changes in the genome have also been induced by vitro high-level mutagenesis of the prototype virus.", "contents": "Assignment of the large oligonucleotides of vesicular stomatitis virus to the N, NS, M, G, and L genes and oligonucleotide gene ordering within the L gene. Analyses of prototype vesicular stomatitis (VSV, Indiana serotype) mRNA-32P-labeled viral RNA duplexes have established the assignments of 65 of the 72 large oligonucleotides that are recovered by two-dimensional electrophoresis of RNase T1 digests of the viral RNA. Fifty of the oligonucleotides are recovered in the L RNA duplex, four each in the N, M, and NS duplexes, and three in the G RNA duplex. Studies of three small defective-particle RNA species indicate that they have only L gene oligonucleotides in addition to three of the seven unassigned oligonucleotides. Some L gene ordering of oligonucleotides can be postulated from the defective-particle RNA sequence analyses. Analyses of naturally occurring alternate isolates of VSV Indiana have established that by comparison to the prototype virus strain, the alternate isolates minimally have genome sequence differences in L, G, N, NS and/or unassigned regions of the genome. Changes in the genome have also been induced by vitro high-level mutagenesis of the prototype virus."}
{"id": "PMID:225511", "title": "Avian sarcoma virus-transformed quail clones defective in the production of focus-forming virus.", "content": "Quail embryo fibroblasts were infected at low multiplicity with avian sarcoma virus, and transformed cells were selected by their ability to form colonies in agar. Five clones that failed to produce focus-forming virus were examined for (i) intactness of the integrated proviral DNA, (ii) intracellular viral RNA production, (iii) intracellular viral antigen production, (iv) production of virus particles, and (v) rescue of a functional src gene and of parental host range determinants by superinfection with Rous-associated virus-60, an avian leukosis virus of subgroup E. Deletions in the integrated viral DNA were apparent in three of the five nonproducer clones. In one clone producing focus-forming virus, analysis of the integrated viral DNA revealed an insertion in the region of the genome that codes for src.", "contents": "Avian sarcoma virus-transformed quail clones defective in the production of focus-forming virus. Quail embryo fibroblasts were infected at low multiplicity with avian sarcoma virus, and transformed cells were selected by their ability to form colonies in agar. Five clones that failed to produce focus-forming virus were examined for (i) intactness of the integrated proviral DNA, (ii) intracellular viral RNA production, (iii) intracellular viral antigen production, (iv) production of virus particles, and (v) rescue of a functional src gene and of parental host range determinants by superinfection with Rous-associated virus-60, an avian leukosis virus of subgroup E. Deletions in the integrated viral DNA were apparent in three of the five nonproducer clones. In one clone producing focus-forming virus, analysis of the integrated viral DNA revealed an insertion in the region of the genome that codes for src."}
{"id": "PMID:225512", "title": "Functional similarity between the early antigens of simian virus 40 and human papovavirus BK.", "content": "The functional properties of the early antigens of simian virus 40 (SV40) and human papovavirus BK (BKV) were investigated. Infection of African green monkey kidney cells with BKV permitted the bidirectional replication of an early temperature-sensitive mutant (tsA) at a nonpermissive temperature. Conceivably, an early gene product (T-antigen) of BKV can substitute functionally for the defective SV40 T-antigen. On the other hand, SV40 DNA replication remained undetectable in human embryonic kidney cells preinfected with BKV, suggesting that BKV early antigens alone are not sufficient to provide for the replication of SV40. Preinfection of African green monkey kidney cells with BKV restored the normal pattern of late lytic SV40 transcription, suppressing the overproduction of early RNA by an SV40 tsA mutant at the nonpermissive temperature. Furthermore, preinfection of African green monkey kidney cells with BKV supported the growth of adenovirus type 2, providing a \"helper function\" similar to that provided by SV40 for the growth of human adenovirus in  monkey kidney cells.", "contents": "Functional similarity between the early antigens of simian virus 40 and human papovavirus BK. The functional properties of the early antigens of simian virus 40 (SV40) and human papovavirus BK (BKV) were investigated. Infection of African green monkey kidney cells with BKV permitted the bidirectional replication of an early temperature-sensitive mutant (tsA) at a nonpermissive temperature. Conceivably, an early gene product (T-antigen) of BKV can substitute functionally for the defective SV40 T-antigen. On the other hand, SV40 DNA replication remained undetectable in human embryonic kidney cells preinfected with BKV, suggesting that BKV early antigens alone are not sufficient to provide for the replication of SV40. Preinfection of African green monkey kidney cells with BKV restored the normal pattern of late lytic SV40 transcription, suppressing the overproduction of early RNA by an SV40 tsA mutant at the nonpermissive temperature. Furthermore, preinfection of African green monkey kidney cells with BKV supported the growth of adenovirus type 2, providing a \"helper function\" similar to that provided by SV40 for the growth of human adenovirus in  monkey kidney cells."}
{"id": "PMID:225513", "title": "Structural studies of retroviruses: characterization of oligomeric complexes of murine and feline leukemia virus envelope and core components formed upon cross-linking.", "content": "To examine the protein proximity and subunit organization of type C retroviruses, preparations of AKR murine leukemia virus were treated with bifunctional cross-linking reagents and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The cross-linked components obtained were characterized by immunoprecipitation with monospecific antisera against purified viral proteins, followed by SDS-PAGE analysis both before and after cleavage of the cross-links. With these procedures, complexes of both viral envelope and core components were identified. The major envelope subunit obtained was a large (apparent molecular weight of 450,000 to 500,000), glycosylated complex, composed of four to six gp70-p15(E) subunits. This complex was detected over a 100-fold range of cross-linker concentration and thus seems to represent a particularly stable viral substructure. The cross-linked complexes of the core proteins consisted of oligomers of p30 dimers, suggesting that the p30 dimer is a basic structural unit of the viral core. When virion preparations, which had previously been disrupted with the nonionic detergent Nonidet P-40, were cross-linked, the envelope complex was still observed, indicating that this structure is stable in the presence of Nonidet P-40. A similar envelope structure was observed for feline leukemia virus, suggesting that such a complex may be a conserved feature of oncornavirus structure.", "contents": "Structural studies of retroviruses: characterization of oligomeric complexes of murine and feline leukemia virus envelope and core components formed upon cross-linking. To examine the protein proximity and subunit organization of type C retroviruses, preparations of AKR murine leukemia virus were treated with bifunctional cross-linking reagents and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The cross-linked components obtained were characterized by immunoprecipitation with monospecific antisera against purified viral proteins, followed by SDS-PAGE analysis both before and after cleavage of the cross-links. With these procedures, complexes of both viral envelope and core components were identified. The major envelope subunit obtained was a large (apparent molecular weight of 450,000 to 500,000), glycosylated complex, composed of four to six gp70-p15(E) subunits. This complex was detected over a 100-fold range of cross-linker concentration and thus seems to represent a particularly stable viral substructure. The cross-linked complexes of the core proteins consisted of oligomers of p30 dimers, suggesting that the p30 dimer is a basic structural unit of the viral core. When virion preparations, which had previously been disrupted with the nonionic detergent Nonidet P-40, were cross-linked, the envelope complex was still observed, indicating that this structure is stable in the presence of Nonidet P-40. A similar envelope structure was observed for feline leukemia virus, suggesting that such a complex may be a conserved feature of oncornavirus structure."}
{"id": "PMID:225514", "title": "Selective isolation of mutants of vesicular stomatitis virus defective in production of the viral glycoprotein.", "content": "We describe a procedure that enriches for temperature-sensitive (ts) mutants of vesicular stomatitis virus (VSV), Indiana serotype, which are conditionally defective in the biosynthesis of the viral glycoprotein. The selection procedure depends on the rescue of pseudotypes of known ts VSV mutants in complementation group V (corresponding to the viral G protein) by growth at 39.5 degrees C in cells preinfected with the avian retrovirus Rous-associated virus 1 (RAV-1). Seventeen nonleaky ts mutants were isolated from mutagenized stocks of VSV. Eight induced no synthesis of VSV proteins at the nonpermissive temperature and hence were not studied further. Four mutants belonged to complementation group V and resembled other ts (V) mutations in their thermolability, production at 39.5 degrees C of noninfectious particles specifically deficient in VSV G protein, synthesis at 39.5 degrees C of normal levels of viral RNA and protein, and ability to be rescued at 39.5 degrees C by preinfection of cells by avian retroviruses. Five new ts mutants were, unexpectedly, in complementation group IV, the putative structural gene for the viral nucleocapsid (N) protein. At 39.5 degrees C these mutants also induced formation of noninfectious particles relatively deficient in G protein, and production of infectious virus at 39.5 degrees C was also enhanced by preinfection with RAV-1, although not to the same extent as in the case of the group V mutants. We believe that the primary effect of the ts mutation is a reduced synthesis of the nucleocapsid and thus an inhibition of synthesis of all viral proteins; apparently, the accumulation of G protein at the surface is not sufficient to envelope all the viral nucleocapsids, or the mutation in the nucleocapsid prevents proper assembly of G into virions. The selection procedure, based on pseudotype formation with glycoproteins encoded by an unrelated virus, has potential use for the isolation of new glycoprotein mutants of diverse groups of enveloped viruses.", "contents": "Selective isolation of mutants of vesicular stomatitis virus defective in production of the viral glycoprotein. We describe a procedure that enriches for temperature-sensitive (ts) mutants of vesicular stomatitis virus (VSV), Indiana serotype, which are conditionally defective in the biosynthesis of the viral glycoprotein. The selection procedure depends on the rescue of pseudotypes of known ts VSV mutants in complementation group V (corresponding to the viral G protein) by growth at 39.5 degrees C in cells preinfected with the avian retrovirus Rous-associated virus 1 (RAV-1). Seventeen nonleaky ts mutants were isolated from mutagenized stocks of VSV. Eight induced no synthesis of VSV proteins at the nonpermissive temperature and hence were not studied further. Four mutants belonged to complementation group V and resembled other ts (V) mutations in their thermolability, production at 39.5 degrees C of noninfectious particles specifically deficient in VSV G protein, synthesis at 39.5 degrees C of normal levels of viral RNA and protein, and ability to be rescued at 39.5 degrees C by preinfection of cells by avian retroviruses. Five new ts mutants were, unexpectedly, in complementation group IV, the putative structural gene for the viral nucleocapsid (N) protein. At 39.5 degrees C these mutants also induced formation of noninfectious particles relatively deficient in G protein, and production of infectious virus at 39.5 degrees C was also enhanced by preinfection with RAV-1, although not to the same extent as in the case of the group V mutants. We believe that the primary effect of the ts mutation is a reduced synthesis of the nucleocapsid and thus an inhibition of synthesis of all viral proteins; apparently, the accumulation of G protein at the surface is not sufficient to envelope all the viral nucleocapsids, or the mutation in the nucleocapsid prevents proper assembly of G into virions. The selection procedure, based on pseudotype formation with glycoproteins encoded by an unrelated virus, has potential use for the isolation of new glycoprotein mutants of diverse groups of enveloped viruses."}
{"id": "PMID:225515", "title": "Polymorphism of avian sarcoma virus src proteins.", "content": "The src gene products of seven different avian sarcoma viruses were compared. In vitro translation of virion RNA yielded products identified unambiguously as p60src in the case of two stocks of the Schmidt-Ruppin strain, three stocks of the Prague strain, the Bryan strain, and the Bratislava 77 strain of avian sarcoma virus. Differences in the electrophoretic mobility of these seven p60src proteins in sodium dodecyl sulfate-polyacrylamide gels, corresponding to variation in the apparent molecular weights ranging from 56,000 to 60,500, were observed. Antigenic variability was also found; only three of the seven viruses tested encoded a p60src, which was precipitated by antisera derived from rabbits bearing tumors induced by the Schmidt-Ruppin strain of Rous sarcoma virus. Examination of the methionine-containing tryptic peptides of the seven ;60src proteins by two-dimensional mapping revealed four common peptides but marked variability in the five to eight other peptides in each protein. Clear differences in the peptide maps of p60src were observed, both between different strains of virus and within strains. In the three cases examined, p60src synthesized in transformed cells was found to be essentially identical to that synthesized in vitro. We conclude that there is significant polymorphism in the p60src proteins of the avian sarcoma viruses.", "contents": "Polymorphism of avian sarcoma virus src proteins. The src gene products of seven different avian sarcoma viruses were compared. In vitro translation of virion RNA yielded products identified unambiguously as p60src in the case of two stocks of the Schmidt-Ruppin strain, three stocks of the Prague strain, the Bryan strain, and the Bratislava 77 strain of avian sarcoma virus. Differences in the electrophoretic mobility of these seven p60src proteins in sodium dodecyl sulfate-polyacrylamide gels, corresponding to variation in the apparent molecular weights ranging from 56,000 to 60,500, were observed. Antigenic variability was also found; only three of the seven viruses tested encoded a p60src, which was precipitated by antisera derived from rabbits bearing tumors induced by the Schmidt-Ruppin strain of Rous sarcoma virus. Examination of the methionine-containing tryptic peptides of the seven ;60src proteins by two-dimensional mapping revealed four common peptides but marked variability in the five to eight other peptides in each protein. Clear differences in the peptide maps of p60src were observed, both between different strains of virus and within strains. In the three cases examined, p60src synthesized in transformed cells was found to be essentially identical to that synthesized in vitro. We conclude that there is significant polymorphism in the p60src proteins of the avian sarcoma viruses."}
{"id": "PMID:225516", "title": "Characterization of a fused protein specified by the adenovirus type 2-simian virus 40 hybrid Ad2+ND1 dp2.", "content": "The adenovirus type 2-simian virus 40 (SV40) hybrid virus Ad2+ND1 dp2 (E. Lukanidin, manuscript in preparation) specified two proteins (molecular weights, 24,000 and 23,000) that are, in part, products of an insertion of SV40 early DNA sequences. This was demonstrated by translation in vitro from viral mRNA that had been selected by hybridization to SV40 DNA. These two phosphorylated, nonvirion proteins were produced late in infection in amounts similar to adenovirus 2 structural proteins and were closely related to each other in tryptic peptide composition. The portion of SV40 DNA (map units 0.17 to 0.22 on the SV40 genome) coding for these proteins was joined to sequences coding for the amino-terminal part of the adenovirus type 2 structural protein IV (fiber). The Ad2+ND1 dp2 23,000- and 24,000-molecular-weight proteins were hybrid polypeptides, with about two-thirds of their tryptic peptides contributed by the fiber protein and the remainder contributed by SV40 T-antigen. They shared with T-antigen (molecular weight, 96,000) a carboxy-terminal proline-rich tryptic peptide. Together, the tryptic peptide composition of these proteins and the known SV40 DNA sequences suggested the reading frame for the translation of T-antigen. The carboxy terminus for T-anigen would then be located on the SV40 genome map next to the TAA terminator triplet at position 0.175, 910 bases away from the cleavage site of the restriction endonuclease EcoRI. Seven host range mutants from Ad2+ND1 dp2 were isolated that had lost the capacity to propagate on monkey cells. They did not induce detectable levels of the hybrid proteins. Three of these mutants had lost the SV40 DNA insertion that codes in part for these proteins. Thus, in analogy to the Ad2+ND1 30,000-molecular-weight protein, the presence of these proteins correlates with the presence of the helper function for adenovirus replication on monkey cells.", "contents": "Characterization of a fused protein specified by the adenovirus type 2-simian virus 40 hybrid Ad2+ND1 dp2. The adenovirus type 2-simian virus 40 (SV40) hybrid virus Ad2+ND1 dp2 (E. Lukanidin, manuscript in preparation) specified two proteins (molecular weights, 24,000 and 23,000) that are, in part, products of an insertion of SV40 early DNA sequences. This was demonstrated by translation in vitro from viral mRNA that had been selected by hybridization to SV40 DNA. These two phosphorylated, nonvirion proteins were produced late in infection in amounts similar to adenovirus 2 structural proteins and were closely related to each other in tryptic peptide composition. The portion of SV40 DNA (map units 0.17 to 0.22 on the SV40 genome) coding for these proteins was joined to sequences coding for the amino-terminal part of the adenovirus type 2 structural protein IV (fiber). The Ad2+ND1 dp2 23,000- and 24,000-molecular-weight proteins were hybrid polypeptides, with about two-thirds of their tryptic peptides contributed by the fiber protein and the remainder contributed by SV40 T-antigen. They shared with T-antigen (molecular weight, 96,000) a carboxy-terminal proline-rich tryptic peptide. Together, the tryptic peptide composition of these proteins and the known SV40 DNA sequences suggested the reading frame for the translation of T-antigen. The carboxy terminus for T-anigen would then be located on the SV40 genome map next to the TAA terminator triplet at position 0.175, 910 bases away from the cleavage site of the restriction endonuclease EcoRI. Seven host range mutants from Ad2+ND1 dp2 were isolated that had lost the capacity to propagate on monkey cells. They did not induce detectable levels of the hybrid proteins. Three of these mutants had lost the SV40 DNA insertion that codes in part for these proteins. Thus, in analogy to the Ad2+ND1 30,000-molecular-weight protein, the presence of these proteins correlates with the presence of the helper function for adenovirus replication on monkey cells."}
{"id": "PMID:225517", "title": "Histone modifications in simian virus 40 and in nucleoprotein complexes containing supercoiled viral DNA.", "content": "Simian virus (SV40) nucleoprotein complexes containing circular supercoiled viral DNA were extracted from infected cells and purified by differential centrifugation. The protein content of these complexes was compared by electrophoresis on 15% acrylamide gels with the protein content of purified SV40 virions and with histones from virus-infected cells. The electrophoretic patterns of histones from each of the sources revealed several major differences. SV40 virions contained histones H3, H2B, H2A, and H4 but not H1. Nucleoprotein complexes and host cells contained all five major histone groups. Relative to cellular histones, virion and nucleoprotein complex histones were enriched 15 to 40% in histones H3 and H4. In addition to the major classes of histones, several subfractions of histones H1, H3, and H4 were observed in acrylamide gels of proteins from SV40 virions and viral nucleoprotein complexes. Acetate labeling experiments indicated that each subfraction of histones H3 and H4 had a different level of acetylation. The histones from SV40 virions and nucleoprotein complexes were acetylated to significantly higher levels than those of infected host cells. No apparent differences in phosphorylation of the major histone groups were observed.", "contents": "Histone modifications in simian virus 40 and in nucleoprotein complexes containing supercoiled viral DNA. Simian virus (SV40) nucleoprotein complexes containing circular supercoiled viral DNA were extracted from infected cells and purified by differential centrifugation. The protein content of these complexes was compared by electrophoresis on 15% acrylamide gels with the protein content of purified SV40 virions and with histones from virus-infected cells. The electrophoretic patterns of histones from each of the sources revealed several major differences. SV40 virions contained histones H3, H2B, H2A, and H4 but not H1. Nucleoprotein complexes and host cells contained all five major histone groups. Relative to cellular histones, virion and nucleoprotein complex histones were enriched 15 to 40% in histones H3 and H4. In addition to the major classes of histones, several subfractions of histones H1, H3, and H4 were observed in acrylamide gels of proteins from SV40 virions and viral nucleoprotein complexes. Acetate labeling experiments indicated that each subfraction of histones H3 and H4 had a different level of acetylation. The histones from SV40 virions and nucleoprotein complexes were acetylated to significantly higher levels than those of infected host cells. No apparent differences in phosphorylation of the major histone groups were observed."}
{"id": "PMID:225518", "title": "Genetic individuality of intracisternal A-particles of Mus musculus.", "content": "The nucleic acid sequence relationship between mouse intracisternal type A-particles and type C and B viruses was examined by reciprocal complementary DNA-RNA hybridization; complementary DNAs prepared from the RNAs of intracisternal A-particles were hybridized with high-molecular-weight RNAs from a variety of murine tumor viruses, and complementary DNAs representing a variety of RNA tumor virus genomes were hybridized with the high-molecular-weight RNAs from A-particles. The criterion for homology between two types of virus was that the heterologous hybridization reaction occurs over the same RNA concentration range as the homologous reacton. The results of these hybridizations indicate that there are no major sequence homologies between the RNA of intracisternal A-particles and the RNA of representative members of type B and C viruses of Mus musculus.", "contents": "Genetic individuality of intracisternal A-particles of Mus musculus. The nucleic acid sequence relationship between mouse intracisternal type A-particles and type C and B viruses was examined by reciprocal complementary DNA-RNA hybridization; complementary DNAs prepared from the RNAs of intracisternal A-particles were hybridized with high-molecular-weight RNAs from a variety of murine tumor viruses, and complementary DNAs representing a variety of RNA tumor virus genomes were hybridized with the high-molecular-weight RNAs from A-particles. The criterion for homology between two types of virus was that the heterologous hybridization reaction occurs over the same RNA concentration range as the homologous reacton. The results of these hybridizations indicate that there are no major sequence homologies between the RNA of intracisternal A-particles and the RNA of representative members of type B and C viruses of Mus musculus."}
{"id": "PMID:225519", "title": "Differences in pathogenicity among cloned sublines of a murine leukemia virus.", "content": "Five clones of the lymphatic leukemia virus 334C were isolated by a procedure designed to maintain homogeneity of the clones. Three of these induced leukemia in mice with the time course of the uncloned parental virus, one induced leukemia with a delayed time course, and one seemed to be biologically inactive. When the clone inducing leukemia most rapidly and the clone inducing leukemia least rapidly were subcloned, the subclones retained the leukemogenicity of the parental clones. The electrophoretic patterns of purified virion proteins and hybridization of viral RNAs with virus-specific DNA suggest that these clones are two closely related variants, not unrelated viruses. Furthermore, in mice infected with these two clones, viral RNA appears in thymuses and spleens at the same time after infection and at nearly the same concentrations. Thus, variations in leukemogenicity can be determined by a genetic property of an ecotropic leukemia virus, and this property is expressed in some manner more subtle than simple control of replication.", "contents": "Differences in pathogenicity among cloned sublines of a murine leukemia virus. Five clones of the lymphatic leukemia virus 334C were isolated by a procedure designed to maintain homogeneity of the clones. Three of these induced leukemia in mice with the time course of the uncloned parental virus, one induced leukemia with a delayed time course, and one seemed to be biologically inactive. When the clone inducing leukemia most rapidly and the clone inducing leukemia least rapidly were subcloned, the subclones retained the leukemogenicity of the parental clones. The electrophoretic patterns of purified virion proteins and hybridization of viral RNAs with virus-specific DNA suggest that these clones are two closely related variants, not unrelated viruses. Furthermore, in mice infected with these two clones, viral RNA appears in thymuses and spleens at the same time after infection and at nearly the same concentrations. Thus, variations in leukemogenicity can be determined by a genetic property of an ecotropic leukemia virus, and this property is expressed in some manner more subtle than simple control of replication."}
{"id": "PMID:225520", "title": "Phosphorylation of murine mammary tumor virus precursor polypeptides.", "content": "Phosphorylation of the murine mammary tumor virus (MuMTV) structural proteins was studied in an MuMTV-infected epithelial cell line derived from a BALB/cf C3H mouse mammary tumor. Immunoprecipitation of 32P-labeled cell extracts with monospecific anti-p27 serum revealed that phosphorylation occurred at the stage of the core-protein polyprotein precursor prp75. Two forms of phosphorylated prp75 were found: one migrating with an apparent molecular weight of 80,000, and the other with a molecular weight of 76,000. The 80,000-molecular-weight species was found to be the most heavily phosphorylated. In addition, a relatively stable phosphorylated processing intermediate of 34,000 molecular weight was observed as well. Tryptic peptide mapping analysis of the 32P-labeled viral proteins indicated a precursor product relationship between the intracellular phosphorylated, high-molecular-weight peptides and the mature MuMTV phosphoproteins p23 and p27. Phosphopeptide analysis also suggested that phosphorylation of the viral proteins occurred in discrete steps and that the attached phosphate groups were conserved throughout the processing steps.", "contents": "Phosphorylation of murine mammary tumor virus precursor polypeptides. Phosphorylation of the murine mammary tumor virus (MuMTV) structural proteins was studied in an MuMTV-infected epithelial cell line derived from a BALB/cf C3H mouse mammary tumor. Immunoprecipitation of 32P-labeled cell extracts with monospecific anti-p27 serum revealed that phosphorylation occurred at the stage of the core-protein polyprotein precursor prp75. Two forms of phosphorylated prp75 were found: one migrating with an apparent molecular weight of 80,000, and the other with a molecular weight of 76,000. The 80,000-molecular-weight species was found to be the most heavily phosphorylated. In addition, a relatively stable phosphorylated processing intermediate of 34,000 molecular weight was observed as well. Tryptic peptide mapping analysis of the 32P-labeled viral proteins indicated a precursor product relationship between the intracellular phosphorylated, high-molecular-weight peptides and the mature MuMTV phosphoproteins p23 and p27. Phosphopeptide analysis also suggested that phosphorylation of the viral proteins occurred in discrete steps and that the attached phosphate groups were conserved throughout the processing steps."}
{"id": "PMID:225521", "title": "Herpes simplex virus type 1 infection of isogenic Epstein-Barr virus genome-negative and -positive Burkitt's lymphoma-derived cell lines.", "content": "The Epstein-Barr virus (EBV) genome-negative Burkitt's lymphoma-derived cell lines BJAB and Ramos and their in vitro EBV-converted sublines BJAB-B1, BJAB-A5, BJAB-B95-8, and AW-Ramos were infected with high multiplicities of herpes simplex virus type 1 (HSV-1; 10 to 70 PFU/cell). Cultures were monitored for cell growth and HSV-1 DNA synthesis. EBV-converted BJAB cultures were more permissive for HSV-1 infection than BJAB cultures. Significant cell killing and HSV-1 DNA synthesis were observed during the first 48 h of infection in the EBV-converted BJAB cultures but not in the BJAB cultures. The EBV-converted BJAB-B1 cell line contains an appreciable fraction of EBV-negative cells. Therefore, it was cloned. EBV-positive and -negative cells were identified by using EBV-determined nuclear antigen anti-complement immunofluorescence. Two types of subclones were identified: (i) those which contained both EBV-determined nuclear antigen-positive and -negative cells and (ii) those which contained only EBV-determined nuclear antigen-negative cells. When levels of HSV-1 DNA synthesis were measured in these subclones, it was found that the former were more permissive for HSV-1 infection than the latter. Thus, the presence of the EBV genome in BJAB cells correlates with increased permissiveness of these cells for HSV-1 during the first 48 h of infection. Nonetheless, persistent HSV-1 infections were established in both BJAB and EBV-converted BJAB-B1 cultures. No differences in extent of permissiveness for HSV-1 infection were found for Ramos and EBV-converted AW-Ramos cells.", "contents": "Herpes simplex virus type 1 infection of isogenic Epstein-Barr virus genome-negative and -positive Burkitt's lymphoma-derived cell lines. The Epstein-Barr virus (EBV) genome-negative Burkitt's lymphoma-derived cell lines BJAB and Ramos and their in vitro EBV-converted sublines BJAB-B1, BJAB-A5, BJAB-B95-8, and AW-Ramos were infected with high multiplicities of herpes simplex virus type 1 (HSV-1; 10 to 70 PFU/cell). Cultures were monitored for cell growth and HSV-1 DNA synthesis. EBV-converted BJAB cultures were more permissive for HSV-1 infection than BJAB cultures. Significant cell killing and HSV-1 DNA synthesis were observed during the first 48 h of infection in the EBV-converted BJAB cultures but not in the BJAB cultures. The EBV-converted BJAB-B1 cell line contains an appreciable fraction of EBV-negative cells. Therefore, it was cloned. EBV-positive and -negative cells were identified by using EBV-determined nuclear antigen anti-complement immunofluorescence. Two types of subclones were identified: (i) those which contained both EBV-determined nuclear antigen-positive and -negative cells and (ii) those which contained only EBV-determined nuclear antigen-negative cells. When levels of HSV-1 DNA synthesis were measured in these subclones, it was found that the former were more permissive for HSV-1 infection than the latter. Thus, the presence of the EBV genome in BJAB cells correlates with increased permissiveness of these cells for HSV-1 during the first 48 h of infection. Nonetheless, persistent HSV-1 infections were established in both BJAB and EBV-converted BJAB-B1 cultures. No differences in extent of permissiveness for HSV-1 infection were found for Ramos and EBV-converted AW-Ramos cells."}
{"id": "PMID:225522", "title": "Product of in vitro translation of the Rous sarcoma virus src gene has protein kinase activity.", "content": "In vitro translation of Rous sarcoma virus virion RNA resulted in the synthesis of a protein kinase which, when immunoprecipitated with antitumor serum, phosphorylated the immunoglobulin heavy chain. Even though in vitro translation of virion RNA resulted in the synthesis of a number of polypeptides which were recognized by antitumor serum, control experiments demonstrated that an immunoprecipitable protein kinase activity was found only when an immunoprecipitable p60src, the polypeptide product of the src gene, was synthesized. A protein kinase with similar properties was therefore intimately associated with p60src which was synthesized in vitro in the reticulocyte lysate, just as it is with p60src which is obtained from transformed chick and mammalian cells. It is therefore highly unlikely that this association is artifactual. ts NY68 is a mutant of Rous sarcoma virus which is able to transform cells at 36 but not at 41 degrees C. In vitro translation of ts NY68 virion RNA at 30 degrees C resulted in efficient synthesis of immunoprecipitable p60src, but very inefficient synthesis of an immunoprecipitable protein kinase. The p60src obtained by in vitro translation of wild-type virion RNA was more than 20-fold more active as a protein kinase than was that obtained from ts NY68 RNA. The correlation in the case of ts NY68 of a deficiency in protein kinase activity with an inability to transform cells at high temperature suggests that the protein kinase activity associated with p60src is indeed critical to cellular transformation.", "contents": "Product of in vitro translation of the Rous sarcoma virus src gene has protein kinase activity. In vitro translation of Rous sarcoma virus virion RNA resulted in the synthesis of a protein kinase which, when immunoprecipitated with antitumor serum, phosphorylated the immunoglobulin heavy chain. Even though in vitro translation of virion RNA resulted in the synthesis of a number of polypeptides which were recognized by antitumor serum, control experiments demonstrated that an immunoprecipitable protein kinase activity was found only when an immunoprecipitable p60src, the polypeptide product of the src gene, was synthesized. A protein kinase with similar properties was therefore intimately associated with p60src which was synthesized in vitro in the reticulocyte lysate, just as it is with p60src which is obtained from transformed chick and mammalian cells. It is therefore highly unlikely that this association is artifactual. ts NY68 is a mutant of Rous sarcoma virus which is able to transform cells at 36 but not at 41 degrees C. In vitro translation of ts NY68 virion RNA at 30 degrees C resulted in efficient synthesis of immunoprecipitable p60src, but very inefficient synthesis of an immunoprecipitable protein kinase. The p60src obtained by in vitro translation of wild-type virion RNA was more than 20-fold more active as a protein kinase than was that obtained from ts NY68 RNA. The correlation in the case of ts NY68 of a deficiency in protein kinase activity with an inability to transform cells at high temperature suggests that the protein kinase activity associated with p60src is indeed critical to cellular transformation."}
{"id": "PMID:225523", "title": "Biochemical studies on the Phlebotomus fever group viruses (Bunyaviridae family).", "content": "Analyses of the virion polypeptides and genomes of several Phlebotomus fever group viruses, Karimabad, Punta Toro, Chagres, and the sandfly fever Sicilian serotype viruses, have established that they are biochemically similar to the accepted members of the Bunyaviridae family. Like snowshoe hare virus (a member of the California serogroup of the Bunyavirus genus of the Bunyaviridae family), Karimabad, Punta Toro, Chagres, and the sandfly fever Sicilian serotype viruses all have three viral RNA species, designated large (L), medium (M), and small (S). Oligonucleotide fingerprint analyses of Karimabad and Punta Toro virus RNA species indicated that their L, M, and S RNA species are unique. By polyacrylamide gel electrophoresis it was determined for Karimabad virus that the apparent molecular weights of its L, M, and S RNA species are 2.6 X 10(6), 2.2 X 10(6), and 0.8 X 10(6), respectively. For Punta Toro virus, the apparent molecular weights of its L, M, and S RNA species are 2.8 X 10(6), 1.8 X 10(6), and 0.75 X 10(6), respectively. The major internal nucleocapsid (N) protein of Karimabad virus was found to have a molecular weight of 21 X 10(3). A similar polypeptide size class was identified in preparations of sandfly fever Sicilian serotype, Chagres, and Punta Toro viruses. The Karimabad virus glycoproteins formed the external surface projections on virus particles and could be removed from virus preparations by protease treatment. The glycoproteins in an unreduced sample could be resolved into two size classes by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. They had apparent molecular weights of 62 X 10(3) and 50 X 10(3) in continuous polyacrylamide gels. When Karimabad virus preparations were reduced with 1% beta-mercaptoethanol, prior to resolution by continuous polyacrylamide gel electrophoresis, all the viral glycoprotein was recovered in a single size class, having an apparent molecular weight of 62 X 10(3). Two or three major virion polypeptides have been identified in preparations of Punta Toro, Chagres, and sandfly fever Sicilian serotype viruses.", "contents": "Biochemical studies on the Phlebotomus fever group viruses (Bunyaviridae family). Analyses of the virion polypeptides and genomes of several Phlebotomus fever group viruses, Karimabad, Punta Toro, Chagres, and the sandfly fever Sicilian serotype viruses, have established that they are biochemically similar to the accepted members of the Bunyaviridae family. Like snowshoe hare virus (a member of the California serogroup of the Bunyavirus genus of the Bunyaviridae family), Karimabad, Punta Toro, Chagres, and the sandfly fever Sicilian serotype viruses all have three viral RNA species, designated large (L), medium (M), and small (S). Oligonucleotide fingerprint analyses of Karimabad and Punta Toro virus RNA species indicated that their L, M, and S RNA species are unique. By polyacrylamide gel electrophoresis it was determined for Karimabad virus that the apparent molecular weights of its L, M, and S RNA species are 2.6 X 10(6), 2.2 X 10(6), and 0.8 X 10(6), respectively. For Punta Toro virus, the apparent molecular weights of its L, M, and S RNA species are 2.8 X 10(6), 1.8 X 10(6), and 0.75 X 10(6), respectively. The major internal nucleocapsid (N) protein of Karimabad virus was found to have a molecular weight of 21 X 10(3). A similar polypeptide size class was identified in preparations of sandfly fever Sicilian serotype, Chagres, and Punta Toro viruses. The Karimabad virus glycoproteins formed the external surface projections on virus particles and could be removed from virus preparations by protease treatment. The glycoproteins in an unreduced sample could be resolved into two size classes by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. They had apparent molecular weights of 62 X 10(3) and 50 X 10(3) in continuous polyacrylamide gels. When Karimabad virus preparations were reduced with 1% beta-mercaptoethanol, prior to resolution by continuous polyacrylamide gel electrophoresis, all the viral glycoprotein was recovered in a single size class, having an apparent molecular weight of 62 X 10(3). Two or three major virion polypeptides have been identified in preparations of Punta Toro, Chagres, and sandfly fever Sicilian serotype viruses."}
{"id": "PMID:225524", "title": "Simian virus 40 t antigen affects the sensitivity of cellular DNA synthesis to theophylline.", "content": "Cellular DNA synthesis induced by simian virus 40 mutants that lack t antigen is sensitive to concentrations of theophylline that do not affect wild-type-induced synthesis.", "contents": "Simian virus 40 t antigen affects the sensitivity of cellular DNA synthesis to theophylline. Cellular DNA synthesis induced by simian virus 40 mutants that lack t antigen is sensitive to concentrations of theophylline that do not affect wild-type-induced synthesis."}
{"id": "PMID:225525", "title": "Neoplastic transformation of cultured Syrian hamster embryo cells by DNA of herpes simplex virus type 2.", "content": "Syrian hamster embryo cells were transformed to a neoplastic phenotype after exposure to herpes simplex virus type 2 (S-1) DNA at concentrations (less than or equal to 0.01 microgram per 60-mm dish) at which infectivity was no longer demonstrable. Transformed cells manifested in vitro phenotypic properties characteristic of the neoplastic state, expressed herpes simplex virus-specific antigens, and induced invasive tumors in vivo. Transfection and transformation of Syrian hamster embryo cells with herpes simplex virus type 2 DNA or its fragments is a suitable system for investigating the structure and function of herpes simplex virus-transforming gene(s).", "contents": "Neoplastic transformation of cultured Syrian hamster embryo cells by DNA of herpes simplex virus type 2. Syrian hamster embryo cells were transformed to a neoplastic phenotype after exposure to herpes simplex virus type 2 (S-1) DNA at concentrations (less than or equal to 0.01 microgram per 60-mm dish) at which infectivity was no longer demonstrable. Transformed cells manifested in vitro phenotypic properties characteristic of the neoplastic state, expressed herpes simplex virus-specific antigens, and induced invasive tumors in vivo. Transfection and transformation of Syrian hamster embryo cells with herpes simplex virus type 2 DNA or its fragments is a suitable system for investigating the structure and function of herpes simplex virus-transforming gene(s)."}
{"id": "PMID:225526", "title": "Transcription of vesicular stomatitis virus is required to shut off cellular RNA synthesis.", "content": "RNA synthesis by mouse myeloma (MPC-11) cells was rapidly and progressively shut off by infection with vesicular stomatitis virus temperature-sensitive (ts) mutants permissive for transcription. In sharp contrast, mutants or defective vesicular stomatitis virions restricted in transcription were incapable of causing progressive inhibition of cellular RNA synthesis even at massive multiplicities of infection. A viral product synthesized 30 to 60 min after permissive infection with tsG114(I) appeared to be essential for prolonged inhibition of RNA synthesis in cells switched up to restrictive temperature.", "contents": "Transcription of vesicular stomatitis virus is required to shut off cellular RNA synthesis. RNA synthesis by mouse myeloma (MPC-11) cells was rapidly and progressively shut off by infection with vesicular stomatitis virus temperature-sensitive (ts) mutants permissive for transcription. In sharp contrast, mutants or defective vesicular stomatitis virions restricted in transcription were incapable of causing progressive inhibition of cellular RNA synthesis even at massive multiplicities of infection. A viral product synthesized 30 to 60 min after permissive infection with tsG114(I) appeared to be essential for prolonged inhibition of RNA synthesis in cells switched up to restrictive temperature."}
{"id": "PMID:225527", "title": "Size of infectious DNA from human and murine cytomegaloviruses.", "content": "Viral DNA was isolated from human and murine cytomegalovirus by equilibrium centrifugation in cesium chloride gradients. The size of the DNA was measured relative to T4 DNA by velocity sedimentation in neutral glycerol gradients, and fractions were assayed for infectious DNA. Infectious murine cytomegalovirus DNA sedimented as a single peak with an estimated molecular weight of 136 X 10(6). Infectious human cytomegalovirus DNA was detected in two peaks with molecular weights of 130 X 10(6) and 150 X 10(6).", "contents": "Size of infectious DNA from human and murine cytomegaloviruses. Viral DNA was isolated from human and murine cytomegalovirus by equilibrium centrifugation in cesium chloride gradients. The size of the DNA was measured relative to T4 DNA by velocity sedimentation in neutral glycerol gradients, and fractions were assayed for infectious DNA. Infectious murine cytomegalovirus DNA sedimented as a single peak with an estimated molecular weight of 136 X 10(6). Infectious human cytomegalovirus DNA was detected in two peaks with molecular weights of 130 X 10(6) and 150 X 10(6)."}
{"id": "PMID:225528", "title": "Identification of mouse mammary tumor virus-specific mRNA.", "content": "Complementary DNA corresponding to the RNA genome of mouse mammary tumor virus was used to identify viral RNA contained in polysomes of a virus-producing mammary tumor cell line. Separation of polysomal mRNA by agarose gel electrophoresis, transfer of the RNA to diazobenzyloxymethyl paper, and hybridization with 32P-labeled mouse mammary tumor virus complementary DNA revealed three viral RNA size classes of 10, 8.8, and 4.4 kilobases in length, respectively.", "contents": "Identification of mouse mammary tumor virus-specific mRNA. Complementary DNA corresponding to the RNA genome of mouse mammary tumor virus was used to identify viral RNA contained in polysomes of a virus-producing mammary tumor cell line. Separation of polysomal mRNA by agarose gel electrophoresis, transfer of the RNA to diazobenzyloxymethyl paper, and hybridization with 32P-labeled mouse mammary tumor virus complementary DNA revealed three viral RNA size classes of 10, 8.8, and 4.4 kilobases in length, respectively."}
{"id": "PMID:225529", "title": "Proteins of vesicular stomatitis virus. V. Identification of a precursor to the phosphoprotein of Piry virus.", "content": "A metabolic precursor to the major phosphoprotein of Piry virus (NSv) has been identified in extracts of Piry virus-infected L cells. The conversion of the precursor NSi to NSv occurs with a half-life of 20 min and is independent of continued protein synthesis. NSi has a greater electrophoretic mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis than does the product NSv, suggesting an increase in molecular weight during maturation. The conversion is unaffected by cyclic AMP, cyclic GMP, or by theophilline and cordycepin. No decrease in isoelectric point of NSv relative to NSi was observed on isoelectric focusing acrylamide gels. These latter observations suggest that NSi and NSv do not differ in extent of phosphorylation. We also report, without further characterization, the identification of another phosphoprotein in Piry virus-infected cells having an electrophoretic mobility in sodium dodecyl sulfate-polyacrylamide gel electrophoresis just slightly greater than the nucleocapsid N protein.", "contents": "Proteins of vesicular stomatitis virus. V. Identification of a precursor to the phosphoprotein of Piry virus. A metabolic precursor to the major phosphoprotein of Piry virus (NSv) has been identified in extracts of Piry virus-infected L cells. The conversion of the precursor NSi to NSv occurs with a half-life of 20 min and is independent of continued protein synthesis. NSi has a greater electrophoretic mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis than does the product NSv, suggesting an increase in molecular weight during maturation. The conversion is unaffected by cyclic AMP, cyclic GMP, or by theophilline and cordycepin. No decrease in isoelectric point of NSv relative to NSi was observed on isoelectric focusing acrylamide gels. These latter observations suggest that NSi and NSv do not differ in extent of phosphorylation. We also report, without further characterization, the identification of another phosphoprotein in Piry virus-infected cells having an electrophoretic mobility in sodium dodecyl sulfate-polyacrylamide gel electrophoresis just slightly greater than the nucleocapsid N protein."}
{"id": "PMID:225530", "title": "Simian virus 40-host cell interaction during lytic infection.", "content": "Both exponentially growing and serum-arrested subcloned CV-1 cell cultures were infected with simian virus 40 (SV40). By 24 h after infection 96% of the nuclei of these permissive cells contained SV40 T-antigen. Analysis of the average DNA content per cell at various times after infection indicated that by 24 h most of the cells contained amounts of DNA similar to those normally found in G(2) cells. Analysis of cell cycle distributions indicated that a G(2) DNA complement was maintained by over 90% of the cells in the infected populations 24 to 48 h postinfection. Cells continued to synthesize SV40 DNA during the first 50 h after infection, and cytopathic effect was first observed 60 h after inoculation. After infection the number of mitotic cells that could be recovered by selective detachment decreased precipitously and was drastically reduced by 24 h. A study of the kinetics of decline in the number of mitotic cells suggests that this decline is related to an event during the cell cycle at or near the G(1)-S-phase border upon which commencement of SV40 DNA replication apparently depends. It was concluded that after SV40 infection, stationary cells are induced to cycle, and cycling cells complete one round of cellular DNA synthesis but do not divide. Although the infected cells continue to synthesize viral DNA, they do not appear able to reinitiate cellular DNA replication units. These results imply that the abundance of T-antigen (produced independently of cell cycle phase) in the presence of the enzymes required for continued DNA synthesis is not sufficient for reinitiation of cellular DNA synthesis.", "contents": "Simian virus 40-host cell interaction during lytic infection. Both exponentially growing and serum-arrested subcloned CV-1 cell cultures were infected with simian virus 40 (SV40). By 24 h after infection 96% of the nuclei of these permissive cells contained SV40 T-antigen. Analysis of the average DNA content per cell at various times after infection indicated that by 24 h most of the cells contained amounts of DNA similar to those normally found in G(2) cells. Analysis of cell cycle distributions indicated that a G(2) DNA complement was maintained by over 90% of the cells in the infected populations 24 to 48 h postinfection. Cells continued to synthesize SV40 DNA during the first 50 h after infection, and cytopathic effect was first observed 60 h after inoculation. After infection the number of mitotic cells that could be recovered by selective detachment decreased precipitously and was drastically reduced by 24 h. A study of the kinetics of decline in the number of mitotic cells suggests that this decline is related to an event during the cell cycle at or near the G(1)-S-phase border upon which commencement of SV40 DNA replication apparently depends. It was concluded that after SV40 infection, stationary cells are induced to cycle, and cycling cells complete one round of cellular DNA synthesis but do not divide. Although the infected cells continue to synthesize viral DNA, they do not appear able to reinitiate cellular DNA replication units. These results imply that the abundance of T-antigen (produced independently of cell cycle phase) in the presence of the enzymes required for continued DNA synthesis is not sufficient for reinitiation of cellular DNA synthesis."}
{"id": "PMID:225531", "title": "Transcription of the Marek's disease virus genome in virus-induced tumors.", "content": "Transcription of the Marek's disease virus (MDV) genome in tumor tissues from MDV-infected chickens has been studied by analyzing the hybridization kinetics of (3)H-labeled MDV DNA with unlabeled RNA extracted from these tissues. Lymphoid tumors of ovary, spleen, liver, and kidney contained MDV genomes, but the virus-specific RNA sequences were transcribed from less than 15% of the viral DNA. A virus nonproductive lymphoblastoid cell line, designated MKT-1, has been established from a kidney lymphoma and contains 15 MDV genomes per cell. In these cells, 12 to 14% of the viral DNA was transcribed. Thus transcription of the MDV genome was restricted both in tumor tissues and MKT-1 cells. A hybridization experiment where RNA extracted from MKT-1 cells and RNA extracted from a spleen tumor were mixed and hybridized to (3)H-labeled MDV DNA indicated that the virus-specific RNAs from the two sources were encoded by the same DNA sequences. The polyribosomal fractions of MKT-1 cells and this spleen tumor contained only a portion of the virus-specific RNA sequences found in whole-cell extracts, indicating the existence of a posttranscriptional control mechanism which prevents the transfer of certain viral RNA transcripts to the polyribosomes. The data suggest that the repressed expression of the viral genome in lymphoid tumor tissues and MKT-1 cells may be the result of precise controls within the cell at the transcriptional and posttranscriptional levels.", "contents": "Transcription of the Marek's disease virus genome in virus-induced tumors. Transcription of the Marek's disease virus (MDV) genome in tumor tissues from MDV-infected chickens has been studied by analyzing the hybridization kinetics of (3)H-labeled MDV DNA with unlabeled RNA extracted from these tissues. Lymphoid tumors of ovary, spleen, liver, and kidney contained MDV genomes, but the virus-specific RNA sequences were transcribed from less than 15% of the viral DNA. A virus nonproductive lymphoblastoid cell line, designated MKT-1, has been established from a kidney lymphoma and contains 15 MDV genomes per cell. In these cells, 12 to 14% of the viral DNA was transcribed. Thus transcription of the MDV genome was restricted both in tumor tissues and MKT-1 cells. A hybridization experiment where RNA extracted from MKT-1 cells and RNA extracted from a spleen tumor were mixed and hybridized to (3)H-labeled MDV DNA indicated that the virus-specific RNAs from the two sources were encoded by the same DNA sequences. The polyribosomal fractions of MKT-1 cells and this spleen tumor contained only a portion of the virus-specific RNA sequences found in whole-cell extracts, indicating the existence of a posttranscriptional control mechanism which prevents the transfer of certain viral RNA transcripts to the polyribosomes. The data suggest that the repressed expression of the viral genome in lymphoid tumor tissues and MKT-1 cells may be the result of precise controls within the cell at the transcriptional and posttranscriptional levels."}
{"id": "PMID:225532", "title": "Characterization of the genome of the murine papovavirus K.", "content": "The DNA genome of the murine papovavirus K virus (KV) was characterized and compared with the genome of polyoma virus. A physical map of the KV genome was constructed by analysis of the size of DNA fragments generated by sequential cleavage with combinations of restriction endonucleases. By using one of the three EcoRI sites in the KV genome as the 0 map position, the KV physical map was then oriented to the polyoma virus genome. Of 42 restriction sites mapped within the KV genome, 7 were localized within 0.01 map unit of their respective sites in the polyoma virus genome; an eighth site mapped within 0.02 map unit. KV replication was examined and found to be bidirectional, initiating at approximately 0.70 map unit. This corresponds well to the origin of replication within the polyoma virus genome and further supports the orientation of the KV physical map.", "contents": "Characterization of the genome of the murine papovavirus K. The DNA genome of the murine papovavirus K virus (KV) was characterized and compared with the genome of polyoma virus. A physical map of the KV genome was constructed by analysis of the size of DNA fragments generated by sequential cleavage with combinations of restriction endonucleases. By using one of the three EcoRI sites in the KV genome as the 0 map position, the KV physical map was then oriented to the polyoma virus genome. Of 42 restriction sites mapped within the KV genome, 7 were localized within 0.01 map unit of their respective sites in the polyoma virus genome; an eighth site mapped within 0.02 map unit. KV replication was examined and found to be bidirectional, initiating at approximately 0.70 map unit. This corresponds well to the origin of replication within the polyoma virus genome and further supports the orientation of the KV physical map."}
{"id": "PMID:225533", "title": "Distinctive RNA transcriptase, polyadenylic acid polymerase, and polyuridylic acid polymerase activities associated with Pichinde virus.", "content": "Three RNA polymerase activities were found and associated with purified Pichinde virus, a member of the Arenaviridae. A heat-labile polymerase activity which required all four ribonucleoside triphosphates for optimal activity co-sedimented on sucrose gradient centrifugation with the viral ribonucleoprotein complex from detergent-disrupted virus preparations. This enzyme synthesized heteropolymers which represented about 23% of the genome RNA as determined by nucleic acid hybridization. Two relatively heat-stable polymerase activities which differed in their cation requirement and substrate specificity were recovered with the virus-associated ribosomes. These polymerase activities synthesized homopolymers of limited chain length: in the presence of 10 mM Mg2%, polyuridylic acid was made, whereas in the presence of 1 mM Mn2%, polyadenylic acid was made. The addition of complementary RNA synthesized with the viral transcriptase in vitro to the reaction mixture containing the polyadenylic acid polymerase activity resulted in the terminal addition of polyadenylic acid to the complementary RNA. The possible function of the ribosome-associated polymerase activities in the replication of the virus is discussed.", "contents": "Distinctive RNA transcriptase, polyadenylic acid polymerase, and polyuridylic acid polymerase activities associated with Pichinde virus. Three RNA polymerase activities were found and associated with purified Pichinde virus, a member of the Arenaviridae. A heat-labile polymerase activity which required all four ribonucleoside triphosphates for optimal activity co-sedimented on sucrose gradient centrifugation with the viral ribonucleoprotein complex from detergent-disrupted virus preparations. This enzyme synthesized heteropolymers which represented about 23% of the genome RNA as determined by nucleic acid hybridization. Two relatively heat-stable polymerase activities which differed in their cation requirement and substrate specificity were recovered with the virus-associated ribosomes. These polymerase activities synthesized homopolymers of limited chain length: in the presence of 10 mM Mg2%, polyuridylic acid was made, whereas in the presence of 1 mM Mn2%, polyadenylic acid was made. The addition of complementary RNA synthesized with the viral transcriptase in vitro to the reaction mixture containing the polyadenylic acid polymerase activity resulted in the terminal addition of polyadenylic acid to the complementary RNA. The possible function of the ribosome-associated polymerase activities in the replication of the virus is discussed."}
{"id": "PMID:225534", "title": "Morphogenesis of foot-and-mouth disease virus. I. Role of procapsids as virion Precursors.", "content": "The role of procapsids during foot-and-mouth disease virus multiplication was studied on infected BHK-21 cells. Purified virus and procapsids were obtained by treating the infected cytoplasmic extracts with RNase and EDTA. The synthesis of virus, procapsids, and total particles was determined in pulse-chase experiments. A precursor-product relationship between procapsids and virions was obtained. The results show that the rate of synthesis of total particles (virus + procapsids) was linear from the addition of the label and was identical to that corresponding to virions. Therefore, the speed of the morphogenetic process as well as the existence of a precursor pool of structural proteins was established. Furthermore, the rate of virus synthesis from procapsids was identical to the rate of synthesis of procapsids from their structural precursors. A quantitative recovery of label from procapsids into virions was obtained by the use of cycloheximide or tosyl-lysine chloromethyl ketone. Under these conditions, virus synthesis proceeds, indicating that these drugs do not affect the morphogenetic step studied in this paper.", "contents": "Morphogenesis of foot-and-mouth disease virus. I. Role of procapsids as virion Precursors. The role of procapsids during foot-and-mouth disease virus multiplication was studied on infected BHK-21 cells. Purified virus and procapsids were obtained by treating the infected cytoplasmic extracts with RNase and EDTA. The synthesis of virus, procapsids, and total particles was determined in pulse-chase experiments. A precursor-product relationship between procapsids and virions was obtained. The results show that the rate of synthesis of total particles (virus + procapsids) was linear from the addition of the label and was identical to that corresponding to virions. Therefore, the speed of the morphogenetic process as well as the existence of a precursor pool of structural proteins was established. Furthermore, the rate of virus synthesis from procapsids was identical to the rate of synthesis of procapsids from their structural precursors. A quantitative recovery of label from procapsids into virions was obtained by the use of cycloheximide or tosyl-lysine chloromethyl ketone. Under these conditions, virus synthesis proceeds, indicating that these drugs do not affect the morphogenetic step studied in this paper."}
{"id": "PMID:225535", "title": "Nucleotide sequence analysis of viable deletion mutants lacking segments of the simian virus 40 genome coding for small t antigen.", "content": "The deletions in nine viable simian virus 40 mutants have been mapped by direct DNA sequence analysis. The mutant DNAs lack small segments of the early region of the viral chromosome (between 0.535 and 0.600 map unit). The deletions are all located in the region which is removed from the large T antigen transcript by splicing. No one deletion removes this entire region, but no part of this segment is conserved in all of the mutants except for several nucleotides near the splice points of the transcript. Although the deletions do not alter the region coding for the large T polypeptide, they do delete portions of the segment coding for the C-terminal half of the small t polypeptide.", "contents": "Nucleotide sequence analysis of viable deletion mutants lacking segments of the simian virus 40 genome coding for small t antigen. The deletions in nine viable simian virus 40 mutants have been mapped by direct DNA sequence analysis. The mutant DNAs lack small segments of the early region of the viral chromosome (between 0.535 and 0.600 map unit). The deletions are all located in the region which is removed from the large T antigen transcript by splicing. No one deletion removes this entire region, but no part of this segment is conserved in all of the mutants except for several nucleotides near the splice points of the transcript. Although the deletions do not alter the region coding for the large T polypeptide, they do delete portions of the segment coding for the C-terminal half of the small t polypeptide."}
{"id": "PMID:225536", "title": "Nucleotide sequence deletions within the coding region for small-t antigen of simian virus 40.", "content": "Simian virus 40 early mutants with deletions mapping in the 0.53-0.60 region have been sequenced by the Maxam and Gilbert approach. All these deletions effect the small-t gene. The size of the shortened small-t-related polypeptides produced by several of the mutants has been compared with the molecular weight as deduced from the nucleotide sequence. There was good agreement for the mutants dl890, dl891, and dl2102. For dl2121 and dl2122 the small-t-related protein was considerably larger than expected. It is possible to explain this result on the basis of the nucleotide sequence: the normal splicing event of the small-t mRNA still occurs, but as the deletion shifts the reading frame, translation of the small-t-related polypeptide continues beyond the small-t splice, but in a different reading frame than large-T. Mutants dl883, dl884, and dl2112 have lost one of the small-t splicing boundaries, and no (or minute amonts of) small-t-related protein has been observed in mutant-infected cells. The possible relationship between splicing and transport of polyadenylic acid-containing mRNA from the nucleus to the cytoplasm in vertebrae cells is discussed.", "contents": "Nucleotide sequence deletions within the coding region for small-t antigen of simian virus 40. Simian virus 40 early mutants with deletions mapping in the 0.53-0.60 region have been sequenced by the Maxam and Gilbert approach. All these deletions effect the small-t gene. The size of the shortened small-t-related polypeptides produced by several of the mutants has been compared with the molecular weight as deduced from the nucleotide sequence. There was good agreement for the mutants dl890, dl891, and dl2102. For dl2121 and dl2122 the small-t-related protein was considerably larger than expected. It is possible to explain this result on the basis of the nucleotide sequence: the normal splicing event of the small-t mRNA still occurs, but as the deletion shifts the reading frame, translation of the small-t-related polypeptide continues beyond the small-t splice, but in a different reading frame than large-T. Mutants dl883, dl884, and dl2112 have lost one of the small-t splicing boundaries, and no (or minute amonts of) small-t-related protein has been observed in mutant-infected cells. The possible relationship between splicing and transport of polyadenylic acid-containing mRNA from the nucleus to the cytoplasm in vertebrae cells is discussed."}
{"id": "PMID:225537", "title": "Simian virus 40 mutants with deletions at the 3' end of the early region are defective in adenovirus helper function.", "content": "Coinfection of monkey cells with simian virus 40 (SV40) and adenovirus type 2 (Ad2) increased the Ad2 yield 1,000-fold over that obtained by Ad2 infection alone of monkey cells (A. S. Rabson, G. T. O'Conor, I. K. Berezesky, and F. J. Paul, Proc. Soc. Exp. Biol. Med. 116:187-190, 1964). The ability of viable mutants of SV40 that contain deletions at various sites in the viral DNA to enhance Ad2 growth in monkey cells was examined. Only those mutants with deletions near the 3' end of the early region were deficient in providing this helper function. Mutants dl1265, lacking 39 base pairs at map position 0.18, and dl1263, lacking 33 base pairs at map position 0.20 (H. van Heuverswyn, C. Cole, P. Berg, and W. Fiers, J. Virol. 30:936-941, 1979), were approximately 4 and 30% as effective as wild-type SV40, respectively. The extent of enhancement of Ad2 yield depended on the multiplicity of infection by SV40, but not by Ad2 (at a multiplicity of infection of </=50), as well as on the relative times of infection by Ad2 and SV40. Increasing the SV40 multiplicity of infection or infecting cells with SV40 wild type or mutants prior to Ad2 infection increased the Ad2 yield dramatically. The T antigens of wild-type SV40, dl1263, and dl1265 were examined. We attempt to correlate defects in helper function, alterations in the T antigen structure, and the DNA sequence of the mutants as determined by van Heuverswyn et al. (J. Virol. 30:936-941, 1979).", "contents": "Simian virus 40 mutants with deletions at the 3' end of the early region are defective in adenovirus helper function. Coinfection of monkey cells with simian virus 40 (SV40) and adenovirus type 2 (Ad2) increased the Ad2 yield 1,000-fold over that obtained by Ad2 infection alone of monkey cells (A. S. Rabson, G. T. O'Conor, I. K. Berezesky, and F. J. Paul, Proc. Soc. Exp. Biol. Med. 116:187-190, 1964). The ability of viable mutants of SV40 that contain deletions at various sites in the viral DNA to enhance Ad2 growth in monkey cells was examined. Only those mutants with deletions near the 3' end of the early region were deficient in providing this helper function. Mutants dl1265, lacking 39 base pairs at map position 0.18, and dl1263, lacking 33 base pairs at map position 0.20 (H. van Heuverswyn, C. Cole, P. Berg, and W. Fiers, J. Virol. 30:936-941, 1979), were approximately 4 and 30% as effective as wild-type SV40, respectively. The extent of enhancement of Ad2 yield depended on the multiplicity of infection by SV40, but not by Ad2 (at a multiplicity of infection of </=50), as well as on the relative times of infection by Ad2 and SV40. Increasing the SV40 multiplicity of infection or infecting cells with SV40 wild type or mutants prior to Ad2 infection increased the Ad2 yield dramatically. The T antigens of wild-type SV40, dl1263, and dl1265 were examined. We attempt to correlate defects in helper function, alterations in the T antigen structure, and the DNA sequence of the mutants as determined by van Heuverswyn et al. (J. Virol. 30:936-941, 1979)."}
{"id": "PMID:225538", "title": "Effect of temperature-sensitive mutation on activity of the RNA transcriptase of vesicular stomatitis virus New Jersey.", "content": "The virion-associated RNA transcriptase activity of vesicular stomatitis virus New Jersey temperature-sensitive (ts) mutants was assayed in vitro at the permissive (31 degrees C) and restrictive (39 degrees C) temperatures. RNA synthesis at 39 degrees C by the RNA-negative ts A1 and the RNA-positive ts C1 and ts D1 mutants was similar to that of wild-type virus. The RNA-negative ts B1 synthesized only small amounts of RNA in vitro at 39 degrees C. The three mutants of complementation group E were dissimilar in the amounts of RNA they synthesized at 39 degrees C: ts E1 synthesized very little RNA, ts E2 synthesized moderate amounts, and RNA synthesis by ts E3 was not inhibited. The two mutants of group F were also dissimilar, since ts F1 synthesized very little RNA at 39 degrees C, whereas ts F2 synthesized as much RNA as wild-type virus. The revertant clones ts B1/R1, ts E1/R1, and ts F1/R1 synthesized RNA at 39 degrees C in amounts comparable to wild-type virus, indicating that the heat sensitivity of the transcriptase activity of the mutants ts B1, ts E1, and ts F1 was associated with temperature sensitivity. Similar heat sensitivities were observed when transcribing nucleoprotein complexes were used in the assays, showing that the mutated polypeptides were part of the viral core. The heat stability of the mutant ts B1 was similar to that of wild-type virus, and in vitro RNA synthesis was fully restored when the temperature was lowered to 31 degrees C after 30 min of preincubation at 39 degrees C, showing that the inhibition was due to reversible configurational change of the mutated polypeptide. When virions of the mutant ts E1 were heated for 5 h at 39 degrees C, their infectivity and transcriptase activity were as stable as those of the wild-type virus, whereas transcriptase activity became very heat labile after disruption of the viral coat with a neutral detergent. This suggests an interaction between the mutated polypeptide and a coat polypeptide which stabilizes the activity of the transcriptase. The RNA transcriptase activity of the mutant ts F1 was also heat labile, although to a lesser extent than that of ts E1. Thus, the defects in transcriptase activity of groups B, E, and F suggest that all three polypeptides of the virus core, polypeptides L, N, and NS, are involved in the transcription. In addition, we postulate that the mutated gene products of groups E and F are multifunctional, being required both in transcription and replication, and that the gene product of group E may also be involved in some late stage of virus development.", "contents": "Effect of temperature-sensitive mutation on activity of the RNA transcriptase of vesicular stomatitis virus New Jersey. The virion-associated RNA transcriptase activity of vesicular stomatitis virus New Jersey temperature-sensitive (ts) mutants was assayed in vitro at the permissive (31 degrees C) and restrictive (39 degrees C) temperatures. RNA synthesis at 39 degrees C by the RNA-negative ts A1 and the RNA-positive ts C1 and ts D1 mutants was similar to that of wild-type virus. The RNA-negative ts B1 synthesized only small amounts of RNA in vitro at 39 degrees C. The three mutants of complementation group E were dissimilar in the amounts of RNA they synthesized at 39 degrees C: ts E1 synthesized very little RNA, ts E2 synthesized moderate amounts, and RNA synthesis by ts E3 was not inhibited. The two mutants of group F were also dissimilar, since ts F1 synthesized very little RNA at 39 degrees C, whereas ts F2 synthesized as much RNA as wild-type virus. The revertant clones ts B1/R1, ts E1/R1, and ts F1/R1 synthesized RNA at 39 degrees C in amounts comparable to wild-type virus, indicating that the heat sensitivity of the transcriptase activity of the mutants ts B1, ts E1, and ts F1 was associated with temperature sensitivity. Similar heat sensitivities were observed when transcribing nucleoprotein complexes were used in the assays, showing that the mutated polypeptides were part of the viral core. The heat stability of the mutant ts B1 was similar to that of wild-type virus, and in vitro RNA synthesis was fully restored when the temperature was lowered to 31 degrees C after 30 min of preincubation at 39 degrees C, showing that the inhibition was due to reversible configurational change of the mutated polypeptide. When virions of the mutant ts E1 were heated for 5 h at 39 degrees C, their infectivity and transcriptase activity were as stable as those of the wild-type virus, whereas transcriptase activity became very heat labile after disruption of the viral coat with a neutral detergent. This suggests an interaction between the mutated polypeptide and a coat polypeptide which stabilizes the activity of the transcriptase. The RNA transcriptase activity of the mutant ts F1 was also heat labile, although to a lesser extent than that of ts E1. Thus, the defects in transcriptase activity of groups B, E, and F suggest that all three polypeptides of the virus core, polypeptides L, N, and NS, are involved in the transcription. In addition, we postulate that the mutated gene products of groups E and F are multifunctional, being required both in transcription and replication, and that the gene product of group E may also be involved in some late stage of virus development."}
{"id": "PMID:225539", "title": "Topography of a flexible ribonucleoprotein helix: protein-protein contacts in Sendai virus nucleocapsids.", "content": "Contacts among the three polypeptide species in the flexible helical nucleocapsids of a paramyxovirus were examined with bifunctional protein cross-linking reagents. Polypeptides L and P, minor components of Sendai virus nucleocapsids implicated in viral RNA polymerase activity, were efficiently cross-linked into large complexes, indicating that they enjoy abundant contacts with neighboring protein molecules in the helix. Less reactivity was found in the case of the major structural polypeptide, NP; about half of all molecules of NP formed large cross-linked complexes, most of the rest remaining as monomers along with a small proportion of homodimers and low-order oligomers. Marked heterogeneity in the cross-linking reactivity of NP molecules, which may reflect the conformational quasi-equivalence inherent in a flexible helix, was indicated by the production of several conformers of homodimers and other low-order oligomers of NP, and by failure of the kinetics of NP cross-linking to conform to a simple statistical model of random polmerization. The validity of the statistical model was shown by cross-linking experiments with the rigid helical virus, tobacco mosaic virus.", "contents": "Topography of a flexible ribonucleoprotein helix: protein-protein contacts in Sendai virus nucleocapsids. Contacts among the three polypeptide species in the flexible helical nucleocapsids of a paramyxovirus were examined with bifunctional protein cross-linking reagents. Polypeptides L and P, minor components of Sendai virus nucleocapsids implicated in viral RNA polymerase activity, were efficiently cross-linked into large complexes, indicating that they enjoy abundant contacts with neighboring protein molecules in the helix. Less reactivity was found in the case of the major structural polypeptide, NP; about half of all molecules of NP formed large cross-linked complexes, most of the rest remaining as monomers along with a small proportion of homodimers and low-order oligomers. Marked heterogeneity in the cross-linking reactivity of NP molecules, which may reflect the conformational quasi-equivalence inherent in a flexible helix, was indicated by the production of several conformers of homodimers and other low-order oligomers of NP, and by failure of the kinetics of NP cross-linking to conform to a simple statistical model of random polmerization. The validity of the statistical model was shown by cross-linking experiments with the rigid helical virus, tobacco mosaic virus."}
{"id": "PMID:225540", "title": "T-antigen expression in proliferating and non-proliferating simian virus 40-transformed mouse cells.", "content": "Previous studies with simian virus 40-transformed mouse 3T3 cells which are temperature sensitive for the expression of the transformed phenotype (ts SV3T3 cells) have shown that T-antigen expression and viral DNA transcription are under cell cycle control. Using these ts SV3T3 cells, we studied the expression of the viral genome under proliferating and non-proliferating conditions, in the presence and absence of inhibitors of macromolecular synthesis and of the tumor promoter phorbol myristate acetate. ts SV3TE cells which are growth arrested at 39 degrees C by low serum concentration or saturation density accumulated in G1 and did not express T-antigen. When these cells were induced to proliferate, at either 32 or 39 degrees C, T-antigen synthesis preceded the entry of the cells into the S-phase and was not coupled to DNA replication. G1-arrested ts SV3T3 cells were induced to synthesize T-antigen by phorbol myristate acetate treatment, but T-antigen alone was not sufficient to induce cellular DNA synthesis. Isoleucine deprivation arrested growth of ts SV3T3 cells, but these cells, as well as normal 3T3, did not accumulate in G1 and continued to express T-antigen. The temperature-sensitive expression of the transformed phenotype in the ts SV3T3 cells does not appear to be due to a lack of transcription of specific regions of the integrated simian virus 40 genome at 39 degrees C.", "contents": "T-antigen expression in proliferating and non-proliferating simian virus 40-transformed mouse cells. Previous studies with simian virus 40-transformed mouse 3T3 cells which are temperature sensitive for the expression of the transformed phenotype (ts SV3T3 cells) have shown that T-antigen expression and viral DNA transcription are under cell cycle control. Using these ts SV3T3 cells, we studied the expression of the viral genome under proliferating and non-proliferating conditions, in the presence and absence of inhibitors of macromolecular synthesis and of the tumor promoter phorbol myristate acetate. ts SV3TE cells which are growth arrested at 39 degrees C by low serum concentration or saturation density accumulated in G1 and did not express T-antigen. When these cells were induced to proliferate, at either 32 or 39 degrees C, T-antigen synthesis preceded the entry of the cells into the S-phase and was not coupled to DNA replication. G1-arrested ts SV3T3 cells were induced to synthesize T-antigen by phorbol myristate acetate treatment, but T-antigen alone was not sufficient to induce cellular DNA synthesis. Isoleucine deprivation arrested growth of ts SV3T3 cells, but these cells, as well as normal 3T3, did not accumulate in G1 and continued to express T-antigen. The temperature-sensitive expression of the transformed phenotype in the ts SV3T3 cells does not appear to be due to a lack of transcription of specific regions of the integrated simian virus 40 genome at 39 degrees C."}
{"id": "PMID:225541", "title": "Cell surface expression of the env gene polyprotein of dual-tropic mink cell focus-forming murine leukemia virus.", "content": "Differences have been observed in the kinetics of processing of the env gene polyprotein of ecotropic, xenotropic, and dual-tropic mink cell focus-forming (MCF) murine leukemia virus. In pulse-chase experiments, the env gene polyprotein of the dural-tropic MCF virus exhibits a marked increase in stability relative to that of either ecotropic or xenotropic virus. A comparison of cell surface expression of env gene products of ecotropic, xenotropic, and dual-tropic MCF murine leukemia virus has been made. Only gp70 is accessible to lactoperoxidase-catalyzed radioiodination of fibroblasts infected by ecotropic or xenotropic virus, whereas both gp70 and the env gene polyprotein are expressed on the surface of dual-tropic MCF virus-infected cells.", "contents": "Cell surface expression of the env gene polyprotein of dual-tropic mink cell focus-forming murine leukemia virus. Differences have been observed in the kinetics of processing of the env gene polyprotein of ecotropic, xenotropic, and dual-tropic mink cell focus-forming (MCF) murine leukemia virus. In pulse-chase experiments, the env gene polyprotein of the dural-tropic MCF virus exhibits a marked increase in stability relative to that of either ecotropic or xenotropic virus. A comparison of cell surface expression of env gene products of ecotropic, xenotropic, and dual-tropic MCF murine leukemia virus has been made. Only gp70 is accessible to lactoperoxidase-catalyzed radioiodination of fibroblasts infected by ecotropic or xenotropic virus, whereas both gp70 and the env gene polyprotein are expressed on the surface of dual-tropic MCF virus-infected cells."}
{"id": "PMID:225542", "title": "Genetics of xenotropic virus expression in mice. I. Evidence for a single locus regulating spontaneous production of infectious virus in crosses involving NZB/B1NJ and 129/J strains of mice.", "content": "The extent of infectious xenotropic virus expression in homogenized splenic tissues from the high-virus-expressing NZB/BINJ mice and the non-virus-expressing 129/J mice and their crosses has been examined. The data suggest that a single autosomal \"dominant-like\" gene controls the spontaneous production and release of infectious xenotropic virus in NZB mice. Analysis of infectious virus production in second-backcross families [(F1 X 129) X 129] confirmed this conclusion. Variations in the amount of X-tropic virus released were evident in all genetic crosses. Virus titers (expressed as focus-forming units per milliliter) of supernatant fluid ranged from high levels in the NZB mice to somewhat lower levels in crosses involving the 129 mice. In the absence of a definite pattern in the titers observed in the genetic crosses studied, the term dominant-like is proposed for the single gene regulating the expression of X-tropic virus in NZB mice.", "contents": "Genetics of xenotropic virus expression in mice. I. Evidence for a single locus regulating spontaneous production of infectious virus in crosses involving NZB/B1NJ and 129/J strains of mice. The extent of infectious xenotropic virus expression in homogenized splenic tissues from the high-virus-expressing NZB/BINJ mice and the non-virus-expressing 129/J mice and their crosses has been examined. The data suggest that a single autosomal \"dominant-like\" gene controls the spontaneous production and release of infectious xenotropic virus in NZB mice. Analysis of infectious virus production in second-backcross families [(F1 X 129) X 129] confirmed this conclusion. Variations in the amount of X-tropic virus released were evident in all genetic crosses. Virus titers (expressed as focus-forming units per milliliter) of supernatant fluid ranged from high levels in the NZB mice to somewhat lower levels in crosses involving the 129 mice. In the absence of a definite pattern in the titers observed in the genetic crosses studied, the term dominant-like is proposed for the single gene regulating the expression of X-tropic virus in NZB mice."}
{"id": "PMID:225543", "title": "Isolation and localization of herpes simplex virus type 1 mRNA.", "content": "Herpes simplex virus (HSV) DNA bound to cellulose has been used as a reagent to isolate viral mRNA for size analysis on denaturing agarose gels. Total viral polysomal polyadenylated RNA was isolated from cells late after infection when such RNA has sequences encoded by approximately 45% of the HSV DNA. This RNA has a size range of from 1.5 to greater than or equal to 8 kilobases, with certain sizes, such as 1.7 to 1.9 kilobases, being favored. We have used the restriction endonucleases HindIII and XbaI singly and together to generate various sized fragments covering the entire HSV-1 genome. These fragments have been bound to cellulose to allow isolation of HSV-1 mRNA annealing to different regions of the viral genome. Discrete sizes of viral mRNA are associated with certain regions of the genome, but the mRNA population hybridizing to even the smallest restriction fragments is complex. We used hybridization of size-fractionated RNA to Southern blots of restriction fragments of HSV-1 DNA generated by the BglII as well as HindIII and XbaI endonucleases to confirm the preparative hybridization data and to provide some overlap data for positioning transcripts. The data of blot and preparative hybridization agreed very well and were combined to construct a preliminary transcription map of HSV-1. Such a map revealed at least two areas of the long unique region of the HSV-1 genome which annealed to a large number of HSV-1 transcripts. Furthermore, discrete-sized mRNA species larger than 5 kilobases in length were found only in the middle of the long unique region. The implications of these data are discussed.", "contents": "Isolation and localization of herpes simplex virus type 1 mRNA. Herpes simplex virus (HSV) DNA bound to cellulose has been used as a reagent to isolate viral mRNA for size analysis on denaturing agarose gels. Total viral polysomal polyadenylated RNA was isolated from cells late after infection when such RNA has sequences encoded by approximately 45% of the HSV DNA. This RNA has a size range of from 1.5 to greater than or equal to 8 kilobases, with certain sizes, such as 1.7 to 1.9 kilobases, being favored. We have used the restriction endonucleases HindIII and XbaI singly and together to generate various sized fragments covering the entire HSV-1 genome. These fragments have been bound to cellulose to allow isolation of HSV-1 mRNA annealing to different regions of the viral genome. Discrete sizes of viral mRNA are associated with certain regions of the genome, but the mRNA population hybridizing to even the smallest restriction fragments is complex. We used hybridization of size-fractionated RNA to Southern blots of restriction fragments of HSV-1 DNA generated by the BglII as well as HindIII and XbaI endonucleases to confirm the preparative hybridization data and to provide some overlap data for positioning transcripts. The data of blot and preparative hybridization agreed very well and were combined to construct a preliminary transcription map of HSV-1. Such a map revealed at least two areas of the long unique region of the HSV-1 genome which annealed to a large number of HSV-1 transcripts. Furthermore, discrete-sized mRNA species larger than 5 kilobases in length were found only in the middle of the long unique region. The implications of these data are discussed."}
{"id": "PMID:225544", "title": "Nature and distribution of feline sarcoma virus nucleotide sequences.", "content": "The genomes of three independent isolates of feline sarcoma virus (FeSV) were compared by molecular hybridization techniques. Using complementary DNAs prepared from two strains, SM- and ST-FeSV, common complementary DNA'S were selected by sequential hybridization to FeSV and feline leukemia virus RNAs. These DNAs were shown to be highly related among the three independent sarcoma virus isolates. FeSV-specific complementary DNAs were prepared by selection for hybridization by the homologous FeSV RNA and against hybridization by fline leukemia virus RNA. Sarcoma virus-specific sequences of SM-FeSV were shown to differ from those of either ST- or GA-FeSV strains, whereas ST-FeSV-specific DNA shared extensive sequence homology with GA-FeSV. By molecular hybridization, each set of FeSV-specific sequences was demonstrated to be present in normal cat cellular DNA in approximately one copy per haploid genome and was conserved throughout Felidae. In contrast, FeSV-common sequences were present in multiple DNA copies and were found only in Mediterranean cats. The present results are consistent with the concept that each FeSV strain has arisen by a mechanism involving recombination between feline leukemia virus and cat cellular DNA sequences, the latter represented within the cat genome in a manner analogous to that of a cellular gene.", "contents": "Nature and distribution of feline sarcoma virus nucleotide sequences. The genomes of three independent isolates of feline sarcoma virus (FeSV) were compared by molecular hybridization techniques. Using complementary DNAs prepared from two strains, SM- and ST-FeSV, common complementary DNA'S were selected by sequential hybridization to FeSV and feline leukemia virus RNAs. These DNAs were shown to be highly related among the three independent sarcoma virus isolates. FeSV-specific complementary DNAs were prepared by selection for hybridization by the homologous FeSV RNA and against hybridization by fline leukemia virus RNA. Sarcoma virus-specific sequences of SM-FeSV were shown to differ from those of either ST- or GA-FeSV strains, whereas ST-FeSV-specific DNA shared extensive sequence homology with GA-FeSV. By molecular hybridization, each set of FeSV-specific sequences was demonstrated to be present in normal cat cellular DNA in approximately one copy per haploid genome and was conserved throughout Felidae. In contrast, FeSV-common sequences were present in multiple DNA copies and were found only in Mediterranean cats. The present results are consistent with the concept that each FeSV strain has arisen by a mechanism involving recombination between feline leukemia virus and cat cellular DNA sequences, the latter represented within the cat genome in a manner analogous to that of a cellular gene."}
{"id": "PMID:225545", "title": "Comparison of the genomes of simian, bovine, and human rotaviruses by gel electrophoresis and detection of genomic variation among bovine isolates.", "content": "By co-electrophoresis in polyacrylamide gels, the segmented double-standed RNA genome of the simian rotavirus, SA 11, was compared with those of human and bovine rotaviruses. A comparison between SA 11 virus and the Northern Ireland cell culture adapted bovine virus showed that the electrophoretic mobilities of each of the 11 corresponding segments differed. In other comparisons, four to seven segment variations were more common. When the genomes of various bovine rotaviruses were compared, eight different electropherotypes were detected. Four of these electropherotypes were obtained from one property during a single outbreak of disease. In view of such genetic diversity, a scheme for the systematic designation of different rotavirus samples is proposed. The significance of the variations in relation to the molecular epidemiology of bovine rotavirus infections is discussed.", "contents": "Comparison of the genomes of simian, bovine, and human rotaviruses by gel electrophoresis and detection of genomic variation among bovine isolates. By co-electrophoresis in polyacrylamide gels, the segmented double-standed RNA genome of the simian rotavirus, SA 11, was compared with those of human and bovine rotaviruses. A comparison between SA 11 virus and the Northern Ireland cell culture adapted bovine virus showed that the electrophoretic mobilities of each of the 11 corresponding segments differed. In other comparisons, four to seven segment variations were more common. When the genomes of various bovine rotaviruses were compared, eight different electropherotypes were detected. Four of these electropherotypes were obtained from one property during a single outbreak of disease. In view of such genetic diversity, a scheme for the systematic designation of different rotavirus samples is proposed. The significance of the variations in relation to the molecular epidemiology of bovine rotavirus infections is discussed."}
{"id": "PMID:225546", "title": "DNA of Epstein-Barr virus. V. Direct repeats of the ends of Epstein-Barr virus DNA.", "content": "Previous data indicated that Epstein-Barr virus DNA is terminated at both ends by direct or inverted repeats of from 1 to 12 copies of a 3 X 10(5)-dalton sequence. Thus, restriction endonuclease fragments which include either terminus vary in size by 3 X 10(5)-dalton increments (D. Given and E. Kieff, J. Virol. 28:524--542, 1978; S. D. Hayward and E. Kieff, J. Virol. 23:421--429, 1977). Furthermore, defined fragments containing either terminus hybridize to each other (Given and Kieff, J. Virol. 28:524--542, 1978). The 5' ends of the DNA are susceptible to lambda exonuclease digestion (Hayward and Kieff, J. Virol. 23:421--429, 1977). To determine whether the terminal DNA is a direct or inverted repeat, the structures formed after denaturation and reannealing of the DNA from one terminus and after annealing of lambda exonuclease-treated DNA were examined in the electron microscope. The data were as follows. (i) No inverted repeats were detected within the SalI D or EcoRI D terminal fragments of Epstein-Barr virus DNA. The absence of \"hairpin- or pan-handle-like\" structures in denatured and partially reannealed preparations of the SalI D or EcoRI D fragment and the absence of repetitive hairpin- or pan-handle-like structures in the free 5' tails of DNA treated with lambda exonuclease indicate that there is no inverted repeat within the 3 X 10(5)-dalton terminal reiteration. (ii) Denatured SalI D or EcoRI D fragments reanneal to form circles ranging in size from 3 X 10(5) to 2.5 X 1O(6) daltons, indicating the presence of multiple direct repeats within this terminus. (iii) Lambda exonuclease treatment of the DNA extracted from virus that had accumulated in the extracellular fluid resulted in asynchronous digestion of ends and extensive internal digestion, probably a consequence of nicks and gaps in the DNA. Most full-length molecules, after 5 min of lambda exonuclease digestion, annealed to form circles, indicating that there exists a direct repeat at both ends of the DNA. (iv) The finding of several circularized molecules with small, largely double-strand circles at the juncture of the ends indicates that the direct repeat at both ends is directly repeated within each end. Hybridization between the direct repeats at the termini is likely to be the mechanism by which Epstein-Barr virus DNA circularizes within infected cells (T. Lindahl, A. Adams, G. Bjursell, G. W. Bornkamm, C. Kaschka-Dierich, and U. Jehn, J. Mol. Biol. 102:511-530, 1976).", "contents": "DNA of Epstein-Barr virus. V. Direct repeats of the ends of Epstein-Barr virus DNA. Previous data indicated that Epstein-Barr virus DNA is terminated at both ends by direct or inverted repeats of from 1 to 12 copies of a 3 X 10(5)-dalton sequence. Thus, restriction endonuclease fragments which include either terminus vary in size by 3 X 10(5)-dalton increments (D. Given and E. Kieff, J. Virol. 28:524--542, 1978; S. D. Hayward and E. Kieff, J. Virol. 23:421--429, 1977). Furthermore, defined fragments containing either terminus hybridize to each other (Given and Kieff, J. Virol. 28:524--542, 1978). The 5' ends of the DNA are susceptible to lambda exonuclease digestion (Hayward and Kieff, J. Virol. 23:421--429, 1977). To determine whether the terminal DNA is a direct or inverted repeat, the structures formed after denaturation and reannealing of the DNA from one terminus and after annealing of lambda exonuclease-treated DNA were examined in the electron microscope. The data were as follows. (i) No inverted repeats were detected within the SalI D or EcoRI D terminal fragments of Epstein-Barr virus DNA. The absence of \"hairpin- or pan-handle-like\" structures in denatured and partially reannealed preparations of the SalI D or EcoRI D fragment and the absence of repetitive hairpin- or pan-handle-like structures in the free 5' tails of DNA treated with lambda exonuclease indicate that there is no inverted repeat within the 3 X 10(5)-dalton terminal reiteration. (ii) Denatured SalI D or EcoRI D fragments reanneal to form circles ranging in size from 3 X 10(5) to 2.5 X 1O(6) daltons, indicating the presence of multiple direct repeats within this terminus. (iii) Lambda exonuclease treatment of the DNA extracted from virus that had accumulated in the extracellular fluid resulted in asynchronous digestion of ends and extensive internal digestion, probably a consequence of nicks and gaps in the DNA. Most full-length molecules, after 5 min of lambda exonuclease digestion, annealed to form circles, indicating that there exists a direct repeat at both ends of the DNA. (iv) The finding of several circularized molecules with small, largely double-strand circles at the juncture of the ends indicates that the direct repeat at both ends is directly repeated within each end. Hybridization between the direct repeats at the termini is likely to be the mechanism by which Epstein-Barr virus DNA circularizes within infected cells (T. Lindahl, A. Adams, G. Bjursell, G. W. Bornkamm, C. Kaschka-Dierich, and U. Jehn, J. Mol. Biol. 102:511-530, 1976)."}
{"id": "PMID:225547", "title": "Neuroblastoma cell fusion by a temperature-sensitive mutant of vesicular stomatitis virus.", "content": "A temperature sensitive mutant of vesicular stomatitis virus which does not mature properly when grown at 39 degrees C promoted extensive fusion of murine neuroblastoma cells at this nonpermissive temperature. Polykaryocytes apparently formed as a result of fusion from within the cells that requires low doses of infectious virions for its promotion and is dependent on viral protein synthesis. Although 90% of infected N-18 neuroblastoma cells were fused by 15 h after infection, larger polykaryocytes continued to form, leading to an average of 28 nuclei per polykaryocyte as a result of polykaryocytes fusing to each other. Two neuroblastoma cell lines have been observed to undergo fusion, whereas three other cell lines (BHK-21, CHO, and 3T3) were incapable of forming polykaryocytes, suggesting that nervous system-derived cells are particularly susceptible to vesicular stomatitis virus-induced fusion. Although the normal assembly of the protein components of this virus is deficient at 39 degrees C, the G glycoprotein was inserted into the infected cell membranes at this temperature. Two lines of evidence suggest that the expression of G at the cell surface promotes this polykaryocyte formation: (i) inhibition of glycosylation, which may be involved in the migration of the G protein to the cellular plasma membranes, will inhibit the cell fusion reaction; (ii) addition of antiserum, directed toward the purified G glycoprotein, will also inhibit cell fusion.", "contents": "Neuroblastoma cell fusion by a temperature-sensitive mutant of vesicular stomatitis virus. A temperature sensitive mutant of vesicular stomatitis virus which does not mature properly when grown at 39 degrees C promoted extensive fusion of murine neuroblastoma cells at this nonpermissive temperature. Polykaryocytes apparently formed as a result of fusion from within the cells that requires low doses of infectious virions for its promotion and is dependent on viral protein synthesis. Although 90% of infected N-18 neuroblastoma cells were fused by 15 h after infection, larger polykaryocytes continued to form, leading to an average of 28 nuclei per polykaryocyte as a result of polykaryocytes fusing to each other. Two neuroblastoma cell lines have been observed to undergo fusion, whereas three other cell lines (BHK-21, CHO, and 3T3) were incapable of forming polykaryocytes, suggesting that nervous system-derived cells are particularly susceptible to vesicular stomatitis virus-induced fusion. Although the normal assembly of the protein components of this virus is deficient at 39 degrees C, the G glycoprotein was inserted into the infected cell membranes at this temperature. Two lines of evidence suggest that the expression of G at the cell surface promotes this polykaryocyte formation: (i) inhibition of glycosylation, which may be involved in the migration of the G protein to the cellular plasma membranes, will inhibit the cell fusion reaction; (ii) addition of antiserum, directed toward the purified G glycoprotein, will also inhibit cell fusion."}
{"id": "PMID:225548", "title": "Multiple copies of Shope virus DNA are present in cells of benign and malignant non-virus-producing neoplasms.", "content": "In an initial efforts to characterize the virological basis of neoplasia in the Shope papilloma-carcinoma system, the extent to which the viral genome is present in non-virus-producing benign and malignant tumors in domestic rabbits was established. Employing nick-translated radioactive viral DNA purified from productively infected papillomas on cotton tail rabbits as a probe, it was found that (i) papillomas, primary carcinomas, and metastatic carcinomas contain 10 to about 100 copies of the viral genome per diploid cell equivalent of DNA and (ii) viral DNA is present in detectable amounts in essentially all neoplastic cells. These results are consistent with the suggestion that continued presence of the viral genome is necessary for induction and maintenance of malignant as well as benign neoplasms.", "contents": "Multiple copies of Shope virus DNA are present in cells of benign and malignant non-virus-producing neoplasms. In an initial efforts to characterize the virological basis of neoplasia in the Shope papilloma-carcinoma system, the extent to which the viral genome is present in non-virus-producing benign and malignant tumors in domestic rabbits was established. Employing nick-translated radioactive viral DNA purified from productively infected papillomas on cotton tail rabbits as a probe, it was found that (i) papillomas, primary carcinomas, and metastatic carcinomas contain 10 to about 100 copies of the viral genome per diploid cell equivalent of DNA and (ii) viral DNA is present in detectable amounts in essentially all neoplastic cells. These results are consistent with the suggestion that continued presence of the viral genome is necessary for induction and maintenance of malignant as well as benign neoplasms."}
{"id": "PMID:225549", "title": "Polyoma DNA synthesis in isolated nuclei: evidence for defective replication forks.", "content": "Nuclei, isolated from polyoma virus-infected mouse 3T6 cells, were incubated under condtions suitable for polyoma DNA synthesis. By using electrom microscopy and standard regression statistics, it was shown that replication is mainly unidirectional in a large number of molecules, indicating the presence of inactive replication forks. The replication forks were inactivated randomly, and the defect seemed to be present from the beginning of the in vitro incubation.", "contents": "Polyoma DNA synthesis in isolated nuclei: evidence for defective replication forks. Nuclei, isolated from polyoma virus-infected mouse 3T6 cells, were incubated under condtions suitable for polyoma DNA synthesis. By using electrom microscopy and standard regression statistics, it was shown that replication is mainly unidirectional in a large number of molecules, indicating the presence of inactive replication forks. The replication forks were inactivated randomly, and the defect seemed to be present from the beginning of the in vitro incubation."}
{"id": "PMID:225550", "title": "Nucleotide sequence analysis of two simian virus 40 mutants with deletions in the region coding for the carboxyl terminus of the T antigen.", "content": "Nucleotide sequence analysis of two simian virus 40 early mutants dl1263 and dl1265, which lack a DNA segment around map positions 0.21 and 0.18, respectively (C. Cole, T. Landers, S. Goff, S. MAnteuil-Brutlag, and P. Berg, J. Virol. 24:277--294, 1977), revealed in-phase deletions of 33 nucleotide pairs for dl1263 and 39 nucleotide paris for dl1265. The 33-base-pair deletion in dl1263 does not correspond to an apparent shortening by 6,000 daltons observed for the mutant T antigen. In dl1265 the normal termination signal as well as most of the proline-rich terminal tryptic peptide has been removed, and the carboxyl terminus of the mutant T antigen is a series of three cysteine residues.", "contents": "Nucleotide sequence analysis of two simian virus 40 mutants with deletions in the region coding for the carboxyl terminus of the T antigen. Nucleotide sequence analysis of two simian virus 40 early mutants dl1263 and dl1265, which lack a DNA segment around map positions 0.21 and 0.18, respectively (C. Cole, T. Landers, S. Goff, S. MAnteuil-Brutlag, and P. Berg, J. Virol. 24:277--294, 1977), revealed in-phase deletions of 33 nucleotide pairs for dl1263 and 39 nucleotide paris for dl1265. The 33-base-pair deletion in dl1263 does not correspond to an apparent shortening by 6,000 daltons observed for the mutant T antigen. In dl1265 the normal termination signal as well as most of the proline-rich terminal tryptic peptide has been removed, and the carboxyl terminus of the mutant T antigen is a series of three cysteine residues."}
{"id": "PMID:225551", "title": "Characterization of pyrimidine deoxyribonucleoside kinase (thymidine kinase) and thymidylate kinase as a multifunctional enzyme in cells transformed by herpes simplex virus type 1 and in cells infected with mutant strains of herpes simplex virus.", "content": "Pyrimidine deoxyribonucleoside kinase (thymidine kinase [TK]) was purified from two herpes simplex virus type 1 (HVS-1)-transformed TK-deficient mouse (LMTK-) cell lines and from LMTK- cells infected with HSV-1 mutant viruses coding for variant TK enzymes. These preparations exhibited normal or variant virus-induced thymidylate kinase activities correlating with their relative TK activities. Neither virus-induced activity was detected in LMTK- cells infected with an HSV-1 TK-deficient mutant. These results suggest that HSV-1 thymidylate kinase activity and TK activity are mediated by the same protein.", "contents": "Characterization of pyrimidine deoxyribonucleoside kinase (thymidine kinase) and thymidylate kinase as a multifunctional enzyme in cells transformed by herpes simplex virus type 1 and in cells infected with mutant strains of herpes simplex virus. Pyrimidine deoxyribonucleoside kinase (thymidine kinase [TK]) was purified from two herpes simplex virus type 1 (HVS-1)-transformed TK-deficient mouse (LMTK-) cell lines and from LMTK- cells infected with HSV-1 mutant viruses coding for variant TK enzymes. These preparations exhibited normal or variant virus-induced thymidylate kinase activities correlating with their relative TK activities. Neither virus-induced activity was detected in LMTK- cells infected with an HSV-1 TK-deficient mutant. These results suggest that HSV-1 thymidylate kinase activity and TK activity are mediated by the same protein."}
{"id": "PMID:225552", "title": "Nucleotide sequence of the self-priming 3' terminus of the single-stranded DNA extracted from the parvovirus Kilham rat virus.", "content": "The parvovirus genome is a linear, single-stranded DNA molecule with double-stranded hairpin termini. The 3' terminus can serve in vitro as a self-primer for the synthesis of a double-stranded viral DNA intermediate. We have sequenced the nucleotides in the 3' terminus and propose a model for the secondary structure of the terminus and the in vitro origin of replication for the complementary viral DNA strand.", "contents": "Nucleotide sequence of the self-priming 3' terminus of the single-stranded DNA extracted from the parvovirus Kilham rat virus. The parvovirus genome is a linear, single-stranded DNA molecule with double-stranded hairpin termini. The 3' terminus can serve in vitro as a self-primer for the synthesis of a double-stranded viral DNA intermediate. We have sequenced the nucleotides in the 3' terminus and propose a model for the secondary structure of the terminus and the in vitro origin of replication for the complementary viral DNA strand."}
{"id": "PMID:225553", "title": "Physical mapping of paar mutations of herpes simplex virus type 1 and type 2 by intertypic marker rescue.", "content": "Mutations (paar) in herpes simplex virus (HSV) which confer resistance to phosphonoacetic acid involve genes associated with virus-induced DNA polymerase activity. Two mutants of HSV (HSV-1 tsH and HSV-2 ts6) produce a thermolabile DNA polymerase activity. In this study, the ts lesions present in these mutants and those present in two independent phosphonoacetic acid-resistant mutants of HSV-1 and HSV-2 (paar-1 and paar-2) have been physically mapped by restriction endonuclease analysis of recombinants produced between HSV-1 and HSV-2 by intertypic marker rescue. All four mutations mapped within a 3.3-kilobase pair region around map unit 40. The accuracy of the method is reflected by the mapping results for tsH and paar-2, which were found to lie in the same 1.3-kilobase pair region. paar-1 was found to lie to the right of ts6. Virus-induced DNA polymerase is thought to have a molecular weight of 150,000, necessitating a gene with a coding capacity of 4.6 kilobase pairs. The four mutations mapped in this study all lie within a region smaller than this, but the results do not yet prove that all four lesions reside in this or any single gene.", "contents": "Physical mapping of paar mutations of herpes simplex virus type 1 and type 2 by intertypic marker rescue. Mutations (paar) in herpes simplex virus (HSV) which confer resistance to phosphonoacetic acid involve genes associated with virus-induced DNA polymerase activity. Two mutants of HSV (HSV-1 tsH and HSV-2 ts6) produce a thermolabile DNA polymerase activity. In this study, the ts lesions present in these mutants and those present in two independent phosphonoacetic acid-resistant mutants of HSV-1 and HSV-2 (paar-1 and paar-2) have been physically mapped by restriction endonuclease analysis of recombinants produced between HSV-1 and HSV-2 by intertypic marker rescue. All four mutations mapped within a 3.3-kilobase pair region around map unit 40. The accuracy of the method is reflected by the mapping results for tsH and paar-2, which were found to lie in the same 1.3-kilobase pair region. paar-1 was found to lie to the right of ts6. Virus-induced DNA polymerase is thought to have a molecular weight of 150,000, necessitating a gene with a coding capacity of 4.6 kilobase pairs. The four mutations mapped in this study all lie within a region smaller than this, but the results do not yet prove that all four lesions reside in this or any single gene."}
{"id": "PMID:225554", "title": "Selective assay for herpes simplex viruses expressing thymidine kinase.", "content": "A technique for selecting herpes simplex viruses expressing the viral thymidine kinase (TK+) from a population of predominantly TK- viruses was developed. This was accomplished by infecting TK- cells and incubating the cultures under a liquid overlay medium containing methotrexate. Since the TK- cells survive in this medium for only a limited period of time, it was necessary to add fresh uninfected TK- cells 48 h after infection. The technique allowed the detection and quantitation of the TK+ virus fraction in mixtures of TK+ and TK- viruses where the TK+ fraction was present in frequencies as low as 10(-5). It was also used to estimate reversion frequencies and to obtain and analyze TK+ revertants from TK- mutant strains of herpes simplex virus type 1.", "contents": "Selective assay for herpes simplex viruses expressing thymidine kinase. A technique for selecting herpes simplex viruses expressing the viral thymidine kinase (TK+) from a population of predominantly TK- viruses was developed. This was accomplished by infecting TK- cells and incubating the cultures under a liquid overlay medium containing methotrexate. Since the TK- cells survive in this medium for only a limited period of time, it was necessary to add fresh uninfected TK- cells 48 h after infection. The technique allowed the detection and quantitation of the TK+ virus fraction in mixtures of TK+ and TK- viruses where the TK+ fraction was present in frequencies as low as 10(-5). It was also used to estimate reversion frequencies and to obtain and analyze TK+ revertants from TK- mutant strains of herpes simplex virus type 1."}
{"id": "PMID:225555", "title": "Regulation of herpesvirus macromolecular synthesis. VIII. The transcription program consists of three phases during which both extent of transcription and accumulation of RNA in the cytoplasm are regulated.", "content": "This report concerns the stable viral RNA sequences that accumulate in HEp-2 cells infected with herpes simplex virus type 1. By hybridizing labeled total DNA and restriction endonuclease DNA fragments with excess unlabeled total nuclear and cytoplasmic RNA, we determined the genetic complexity of the RNA and we mapped the regions on the physical map of herpes simplex virus type 1 DNA that are homologous to the RNA. Our results show the following. (i) The viral RNAs accumulating in the nucleus and cytoplasm of cells infected and maintained in the presence of inhibitory concentrations of either cycloheximide or emetine were homologous to 33 and 12% of viral DNA, respectively. All of the fragments tested contained sequences homologous to nuclear RNA. However, only the fragments mapping between 0.00 and 0.18, and 0.53 and 1.00 map units contained sequences homologous to cytoplasmic RNA. (ii) The viral RNAs that accumulate in the nucleus and cytoplasm of cells infected and maintained in the presence of inhibitory concentrations of phoaphonoacetic acid were homologous to 39 and 26% of viral DNA, respectively. In this instance all of the fragments except those mapping between 0.42 and 0.53 map units contained sequences homologous to cytoplasmic RNA. (iii) The viral RNAs that accumulate in the nucleus and cytoplasm 8 h after infection were homologous to greater than 50 and 41%, respectively. All of the fragments tested contained sequences homologous to cytoplasmic RNA. (iv) The viral RNAs that accumulate in the nucleus and cytoplasm of cells infected and maintained in the presence of canavanine are homologous to 33 and 19% of viral DNA, respectively. All of the fragments tested contained sequences homologous to both nuclear and cytoplasmic RNAs. Our results indicate the following. First, there are at least three phases of transcription of viral DNA. Phase 1 does not require the synthesis of host cell or viral proteins. Phase 2 requires the synthesis of viral proteins made before the initiation of viral DNA synthesis. Phase 3 appears to be related to the initiation of viral DNA synthesis. Second, both the extent of transcription and the accumulation of viral RNA in the cytoplasm are tightly regulated. The genetic complexity of total RNA accumulating in infected cells increased in each successive phase. Moreover, the genetic complexity of nuclear RNA was invariably higher than that of cytoplasmic RNA in each phase. Lastly, the results of the studies on viral RNA accumulating in canavanine-treated cells reinforce the hypothesis made previously that more than one polypeptide in each of the alpha and beta polypeptide groups is involved in the transcription preceding the transitions from alpha to beta and beta to gamma polypeptide synthesis, respectively, and that canavanine selectively inactivated subsets of these polypeptides permitting only partial transitions from alpha to beta and beta to gamma to occur.", "contents": "Regulation of herpesvirus macromolecular synthesis. VIII. The transcription program consists of three phases during which both extent of transcription and accumulation of RNA in the cytoplasm are regulated. This report concerns the stable viral RNA sequences that accumulate in HEp-2 cells infected with herpes simplex virus type 1. By hybridizing labeled total DNA and restriction endonuclease DNA fragments with excess unlabeled total nuclear and cytoplasmic RNA, we determined the genetic complexity of the RNA and we mapped the regions on the physical map of herpes simplex virus type 1 DNA that are homologous to the RNA. Our results show the following. (i) The viral RNAs accumulating in the nucleus and cytoplasm of cells infected and maintained in the presence of inhibitory concentrations of either cycloheximide or emetine were homologous to 33 and 12% of viral DNA, respectively. All of the fragments tested contained sequences homologous to nuclear RNA. However, only the fragments mapping between 0.00 and 0.18, and 0.53 and 1.00 map units contained sequences homologous to cytoplasmic RNA. (ii) The viral RNAs that accumulate in the nucleus and cytoplasm of cells infected and maintained in the presence of inhibitory concentrations of phoaphonoacetic acid were homologous to 39 and 26% of viral DNA, respectively. In this instance all of the fragments except those mapping between 0.42 and 0.53 map units contained sequences homologous to cytoplasmic RNA. (iii) The viral RNAs that accumulate in the nucleus and cytoplasm 8 h after infection were homologous to greater than 50 and 41%, respectively. All of the fragments tested contained sequences homologous to cytoplasmic RNA. (iv) The viral RNAs that accumulate in the nucleus and cytoplasm of cells infected and maintained in the presence of canavanine are homologous to 33 and 19% of viral DNA, respectively. All of the fragments tested contained sequences homologous to both nuclear and cytoplasmic RNAs. Our results indicate the following. First, there are at least three phases of transcription of viral DNA. Phase 1 does not require the synthesis of host cell or viral proteins. Phase 2 requires the synthesis of viral proteins made before the initiation of viral DNA synthesis. Phase 3 appears to be related to the initiation of viral DNA synthesis. Second, both the extent of transcription and the accumulation of viral RNA in the cytoplasm are tightly regulated. The genetic complexity of total RNA accumulating in infected cells increased in each successive phase. Moreover, the genetic complexity of nuclear RNA was invariably higher than that of cytoplasmic RNA in each phase. Lastly, the results of the studies on viral RNA accumulating in canavanine-treated cells reinforce the hypothesis made previously that more than one polypeptide in each of the alpha and beta polypeptide groups is involved in the transcription preceding the transitions from alpha to beta and beta to gamma polypeptide synthesis, respectively, and that canavanine selectively inactivated subsets of these polypeptides permitting only partial transitions from alpha to beta and beta to gamma to occur."}
{"id": "PMID:225556", "title": "DNA of Epstein-Barr virus. VI. Mapping of the internal tandem reiteration.", "content": "Epstein-Barr virus (B95-8) DNA consists of short (10 X 10(6)) and long (87 X 10(6)) unique DNA sequences joined by 10 tandem reiterations of a 1.85 X 10(6) DNA segment. The reiterated sequence contains BamI and BglII sites separated by 4 X 10(5). The 4.5 X 10(5) and 14.0 X 10(5) segments generated by cleavage of the reiterated DNA with BamI and BglII contain sequences which hybridize to each other, suggesting that the internal tandemly reiterated sequence has a direct or inverted repeat within it. The opposite ends of the linear, nicked, double-stranded DNA molecule (R. F. Pritchett, S. D. Hayward, and E. D. Kieff, J. Virol. 15:556--569, 1975) consist of from 1 to 12 direct repeats of another 3 X 10(5) sequence (D. Given and E. Kieff, J. Virol. 28:524--542, 1978; D. Given, D. Yee, K. Griem, and E. Kieff, J. Virol. 30:852--862, 1979). There is no homology between the internal reiterated sequence and either terminus. However, part of the internal reiteration (less than 5 X 10(5) is reiterated at two separate locations in the long unique region. The internal reiterations are a source of variation within EBV (B95-8) DNA preparations. Thus, although the majority of molecules contain 10 tandem reiterations, some molecules have 9, 8, 7, 6, 5, 4, or fewer tandem reiterations. A consequence of this variability is that the KpnI A fragment and the EcoRI/Hsul A fragment consist of a family of seven or more fragments differing in the number of tandem internal reiterations. The EcoRI/HsuI A fragment of EBV (W91) DNA is approximately 6 X 10(6) smaller than the largest and dominant EcoRI/HsuI A fragment of EBV (B95-8) DNA. EBV (W91 DNA also differs from EBV (B95-8) DNA by an additional 7 X 10(6) to 8 X 10(6) of DNA in the long unique DNA region (D. Given and E. Kieff, J. Virol. 28:524--542, 1978; N. Raab-Traub, R. Pritchett, and E. Kieff, J. Virol. 27:388--398, 1978). These data suggest the possibility that the smaller number of internal reiterations in EBV (W91) DNA may be a consequence of the additional unique DNA and a restriction in the overall size of EBV DNA.", "contents": "DNA of Epstein-Barr virus. VI. Mapping of the internal tandem reiteration. Epstein-Barr virus (B95-8) DNA consists of short (10 X 10(6)) and long (87 X 10(6)) unique DNA sequences joined by 10 tandem reiterations of a 1.85 X 10(6) DNA segment. The reiterated sequence contains BamI and BglII sites separated by 4 X 10(5). The 4.5 X 10(5) and 14.0 X 10(5) segments generated by cleavage of the reiterated DNA with BamI and BglII contain sequences which hybridize to each other, suggesting that the internal tandemly reiterated sequence has a direct or inverted repeat within it. The opposite ends of the linear, nicked, double-stranded DNA molecule (R. F. Pritchett, S. D. Hayward, and E. D. Kieff, J. Virol. 15:556--569, 1975) consist of from 1 to 12 direct repeats of another 3 X 10(5) sequence (D. Given and E. Kieff, J. Virol. 28:524--542, 1978; D. Given, D. Yee, K. Griem, and E. Kieff, J. Virol. 30:852--862, 1979). There is no homology between the internal reiterated sequence and either terminus. However, part of the internal reiteration (less than 5 X 10(5) is reiterated at two separate locations in the long unique region. The internal reiterations are a source of variation within EBV (B95-8) DNA preparations. Thus, although the majority of molecules contain 10 tandem reiterations, some molecules have 9, 8, 7, 6, 5, 4, or fewer tandem reiterations. A consequence of this variability is that the KpnI A fragment and the EcoRI/Hsul A fragment consist of a family of seven or more fragments differing in the number of tandem internal reiterations. The EcoRI/HsuI A fragment of EBV (W91) DNA is approximately 6 X 10(6) smaller than the largest and dominant EcoRI/HsuI A fragment of EBV (B95-8) DNA. EBV (W91 DNA also differs from EBV (B95-8) DNA by an additional 7 X 10(6) to 8 X 10(6) of DNA in the long unique DNA region (D. Given and E. Kieff, J. Virol. 28:524--542, 1978; N. Raab-Traub, R. Pritchett, and E. Kieff, J. Virol. 27:388--398, 1978). These data suggest the possibility that the smaller number of internal reiterations in EBV (W91) DNA may be a consequence of the additional unique DNA and a restriction in the overall size of EBV DNA."}
{"id": "PMID:225557", "title": "Temperature-sensitive mutants of complementation group E of vesicular stomatitis virus New Jersey serotype possess altered NS polypeptides.", "content": "In vesicular stomatitis virus New Jersey serotype polyacrylamide gel electrophoresis was unable to distinguish the polypeptides of the temperature-sensitive (ts) mutants of complementation groups A, B, C, and F from those of the wild-type virus. However, the NS polypeptide of the representative mutant of group E, ts E1, had a significantly greater electrophoretic mobility than that of the wild-type virus NS polypeptide. The electrophoretic mobilities of the NS polypeptides of the three mutants of complementation group E varied, being greatest in the case of ts E1, slightly less for ts E2, and only a little greater than that of wild-type virus NS polypeptide in the case of ts E3. Since the NS polypeptides of the revertant clones ts E1/R1 and ts E3/R1 have mobilities identical to that of wild-type NS polypeptide, the observed altered mobilities of the group E mutants are almost certainly the direct result of the ts mutations in the E locus. The electrophoretic mobilities of the intracellular NS polypeptides of the group E mutants were indistinguishable from those of their virion NS polypeptides. The electrophoretic mobilities of the NS polypeptides of the group E mutants synthesized in vitro using mRNA synthesized in vitro by TNP were identical to those of the NS polypeptides of their purified virions. The NS polypeptides of all three mutants were labeled with (32)P(i) to approximately the same extent as wild-type virus NS polypeptide, indicating that gross differences in phosphorylation of this polypeptide are unlikely to account for the altered mobilities. We propose a model in which the NS polypeptide consists of at least three loops held in this configuration by hydrophobic or ionic forces or both and stabilized by phosphodiester bridges. If a mutation affects one of the amino acids to which the phosphate is covalently linked, the phosphodiester bridge cannot be formed, and, as a result, in the presence of sodium dodecyl sulfate the affected loop opens and thus the NS polypeptide migrates further into the gel. Such a configuration may also explain the multifunctional nature of the NS polypeptide.", "contents": "Temperature-sensitive mutants of complementation group E of vesicular stomatitis virus New Jersey serotype possess altered NS polypeptides. In vesicular stomatitis virus New Jersey serotype polyacrylamide gel electrophoresis was unable to distinguish the polypeptides of the temperature-sensitive (ts) mutants of complementation groups A, B, C, and F from those of the wild-type virus. However, the NS polypeptide of the representative mutant of group E, ts E1, had a significantly greater electrophoretic mobility than that of the wild-type virus NS polypeptide. The electrophoretic mobilities of the NS polypeptides of the three mutants of complementation group E varied, being greatest in the case of ts E1, slightly less for ts E2, and only a little greater than that of wild-type virus NS polypeptide in the case of ts E3. Since the NS polypeptides of the revertant clones ts E1/R1 and ts E3/R1 have mobilities identical to that of wild-type NS polypeptide, the observed altered mobilities of the group E mutants are almost certainly the direct result of the ts mutations in the E locus. The electrophoretic mobilities of the intracellular NS polypeptides of the group E mutants were indistinguishable from those of their virion NS polypeptides. The electrophoretic mobilities of the NS polypeptides of the group E mutants synthesized in vitro using mRNA synthesized in vitro by TNP were identical to those of the NS polypeptides of their purified virions. The NS polypeptides of all three mutants were labeled with (32)P(i) to approximately the same extent as wild-type virus NS polypeptide, indicating that gross differences in phosphorylation of this polypeptide are unlikely to account for the altered mobilities. We propose a model in which the NS polypeptide consists of at least three loops held in this configuration by hydrophobic or ionic forces or both and stabilized by phosphodiester bridges. If a mutation affects one of the amino acids to which the phosphate is covalently linked, the phosphodiester bridge cannot be formed, and, as a result, in the presence of sodium dodecyl sulfate the affected loop opens and thus the NS polypeptide migrates further into the gel. Such a configuration may also explain the multifunctional nature of the NS polypeptide."}
{"id": "PMID:225558", "title": "Growth state of the cell early after infection with simian virus 40 determines whether the maintenance of transformation will be A-gene dependent or independent.", "content": "The existence of both temperature-sensitive (N) and temperature-insensitive (A) rat transformants, isolated after infection with simian virus 40 tsA mutant, is reported. Both types can be isolated as dense foci. Foci appearing after infection of rapidly growing cells were temperature sensitive. Infection of cells arrested at confluence gave rise to foci that were temperature insensitive. Transformants isolated by the agar assay (conditions under which normal cells are unable to grow) were also temperature-insensitive. N-transformants remained temperature sensitive upon entering the resting state at the restrictive temperature and upon re-entering the growth cycle at the permissive temperature. They also remained temperature sensitive under a variety of conditions restrictive for nontransformed cells. Thus, the state of the cell in the first few days after infection fixes the cells. Thus, the state of the cell in the first few days after infection fixes the cell as an N- or A-transformant. Various models for transformation are discussed, including one proposing that the virus interacts in two ways with a central cell mechanism controlling growth. The maintenance of the transformed phenotype would be dependent on T-antigen in N-transformants but independent of T-antigen in A-transformants.", "contents": "Growth state of the cell early after infection with simian virus 40 determines whether the maintenance of transformation will be A-gene dependent or independent. The existence of both temperature-sensitive (N) and temperature-insensitive (A) rat transformants, isolated after infection with simian virus 40 tsA mutant, is reported. Both types can be isolated as dense foci. Foci appearing after infection of rapidly growing cells were temperature sensitive. Infection of cells arrested at confluence gave rise to foci that were temperature insensitive. Transformants isolated by the agar assay (conditions under which normal cells are unable to grow) were also temperature-insensitive. N-transformants remained temperature sensitive upon entering the resting state at the restrictive temperature and upon re-entering the growth cycle at the permissive temperature. They also remained temperature sensitive under a variety of conditions restrictive for nontransformed cells. Thus, the state of the cell in the first few days after infection fixes the cells. Thus, the state of the cell in the first few days after infection fixes the cell as an N- or A-transformant. Various models for transformation are discussed, including one proposing that the virus interacts in two ways with a central cell mechanism controlling growth. The maintenance of the transformed phenotype would be dependent on T-antigen in N-transformants but independent of T-antigen in A-transformants."}
{"id": "PMID:225559", "title": "Regulation of simian virus 40 transcription: sensitive analysis of the RNA species present early in infections by virus or viral DNA.", "content": "We have examined the discrete species of simian virus 40 (SV40) RNA present very early in infection of monkey cells with wild-type virus, with mutant tsA58 virus, and with the corresponding DNAs to distinguish between two classes of models for control of late transcription: (i) positive control mediated by large-T antigen and (ii) negative control mediated by a repressor protein associated with viral DNA in the virion. Total cytoplasmic or nuclear polyadenylated RNAs from infected cells were denatured with glyoxal, separated by electrophoresis on agarose gels, and transferred to diazobenzyloxymethyl paper. The positions of specific early and late RNA species were determined with region-specific SV40 DNA probes. The technique can detect individual RNAs present at the level of less than one copy per cell. After 9.5 h at 37 degrees C, appreciable amounts of two early RNAs (2.6 kilobases [kb] and 2.9 kb) were present in the cytoplasm of cells infected with wild-type virus or DNA, along with much smaller amounts of two late RNAs, 1.6 kb (16S) and 2.5 kb (19S). The amounts of the late RNAs were reduced, but they were still synthesized in the presence of cytosine arabinoside, an inhibitor of DNA synthesis. In comparable infections with tsA58 virus or DNA at nonpermissive temperature (41 degrees C), substantial amounts of the two early RNAs were again present, but the two late RNAs could not be detected. However, small amounts of the late RNAs were found when infections with tsA58 virus or DNA were prolonged to 30 h at 41 degrees C. These results are not consistent with negative control of late transcription through the action of a repressor and, taken together with other data, suggest that T antigen has an active role in late RNA synthesis. Specific early and late viral RNAs were also detected in the nuclear poly(A)(+) fractions and were similar in size to the RNA species found in the cytoplasmic polyadenylated fractions. The late nuclear RNAs (1.8 and 2.9 kb) were significantly larger than the late cytoplasmic species, possibly because they are precursors. The 2.6- and 2.9-kb early RNAs found in the cytoplasm are probably the messengers for large-T and small-t antigens, respectively.", "contents": "Regulation of simian virus 40 transcription: sensitive analysis of the RNA species present early in infections by virus or viral DNA. We have examined the discrete species of simian virus 40 (SV40) RNA present very early in infection of monkey cells with wild-type virus, with mutant tsA58 virus, and with the corresponding DNAs to distinguish between two classes of models for control of late transcription: (i) positive control mediated by large-T antigen and (ii) negative control mediated by a repressor protein associated with viral DNA in the virion. Total cytoplasmic or nuclear polyadenylated RNAs from infected cells were denatured with glyoxal, separated by electrophoresis on agarose gels, and transferred to diazobenzyloxymethyl paper. The positions of specific early and late RNA species were determined with region-specific SV40 DNA probes. The technique can detect individual RNAs present at the level of less than one copy per cell. After 9.5 h at 37 degrees C, appreciable amounts of two early RNAs (2.6 kilobases [kb] and 2.9 kb) were present in the cytoplasm of cells infected with wild-type virus or DNA, along with much smaller amounts of two late RNAs, 1.6 kb (16S) and 2.5 kb (19S). The amounts of the late RNAs were reduced, but they were still synthesized in the presence of cytosine arabinoside, an inhibitor of DNA synthesis. In comparable infections with tsA58 virus or DNA at nonpermissive temperature (41 degrees C), substantial amounts of the two early RNAs were again present, but the two late RNAs could not be detected. However, small amounts of the late RNAs were found when infections with tsA58 virus or DNA were prolonged to 30 h at 41 degrees C. These results are not consistent with negative control of late transcription through the action of a repressor and, taken together with other data, suggest that T antigen has an active role in late RNA synthesis. Specific early and late viral RNAs were also detected in the nuclear poly(A)(+) fractions and were similar in size to the RNA species found in the cytoplasmic polyadenylated fractions. The late nuclear RNAs (1.8 and 2.9 kb) were significantly larger than the late cytoplasmic species, possibly because they are precursors. The 2.6- and 2.9-kb early RNAs found in the cytoplasm are probably the messengers for large-T and small-t antigens, respectively."}
{"id": "PMID:225560", "title": "Cell killing by spleen necrosis virus is correlated with a transient accumulation of spleen necrosis virus DNA.", "content": "Spleen necrosis virus productively infects avian and rat cells. The average number of molecules of unintegrated and integrated viral DNA in cells at different times after infection was determined by hybridization and transfection assays. Shortly after infection, there was a transient accumulation of an average of about 150 to 200 molecules of unintegrated linear spleen necrosis virus DNA per chicken, turkey, or pheasant cell. No such accumulation was seen in infected rat cells. Soon after infection there was in chicken cells, but not inturkey, pheasant, or rat cells, also a transient integration of an average of 35 copies of viral DNA per cell. By 10 days after infection, the majority of this integrated viral DNA was lost from the population of infected chicken cells. At the same time, the majority of the unintegrated viral DNA was also lost from infected chicken, turkey, and pheasant cells. The transient cytopathic effect seen in these infected cells also occurred at this time. Late after infection about five copies of apparently nondefective spleen necrosis proviruses were stably integrated at multiple sites in chicken, turkey, pheasant, and rat DNA. These results demonstrate a correlation between the transient accumulation of large numbers of spleen necrosis virus DNA molecules and the transient occurrence of cytopathic effects.", "contents": "Cell killing by spleen necrosis virus is correlated with a transient accumulation of spleen necrosis virus DNA. Spleen necrosis virus productively infects avian and rat cells. The average number of molecules of unintegrated and integrated viral DNA in cells at different times after infection was determined by hybridization and transfection assays. Shortly after infection, there was a transient accumulation of an average of about 150 to 200 molecules of unintegrated linear spleen necrosis virus DNA per chicken, turkey, or pheasant cell. No such accumulation was seen in infected rat cells. Soon after infection there was in chicken cells, but not inturkey, pheasant, or rat cells, also a transient integration of an average of 35 copies of viral DNA per cell. By 10 days after infection, the majority of this integrated viral DNA was lost from the population of infected chicken cells. At the same time, the majority of the unintegrated viral DNA was also lost from infected chicken, turkey, and pheasant cells. The transient cytopathic effect seen in these infected cells also occurred at this time. Late after infection about five copies of apparently nondefective spleen necrosis proviruses were stably integrated at multiple sites in chicken, turkey, pheasant, and rat DNA. These results demonstrate a correlation between the transient accumulation of large numbers of spleen necrosis virus DNA molecules and the transient occurrence of cytopathic effects."}
{"id": "PMID:225561", "title": "Suppression of multiplication of avian sarcoma virus by rapid spread of transformation-defective virus of the same subgroup.", "content": "We have tested the hypothesis that some transformation-defective (td) viruses grow faster than the avian sarcoma viruses (ASV) from which they are derived, resulting in establishment of interference by the td virus and suppression of the ASV multiplication. Using an ASV of subgroup A (ASV-A) that does not contain td virus and an independently isolated tdASV-A, we performed separate and mixed infections to test this hypothesis. At multiplicities of 1 or less, tdASV alone grew to higher titers and more rapidly than ASV alone. In mixed infections at low multiplicities that allowed spread of progeny virus, when as little as 10% of the virus inoculum was td virus, there was an excess of td virus by 2 days after infection and a decrease in the titer of ASV relative to a control infection with no td virus. In mixed infections at high multiplicities which minimized spread of progeny virus, there was no excess of td virus and the titer of ASV was not decreased relative to the control infection with no td virus. These data support the hypothesis that we proposed and indicate that deletions in the ASV src gene may not be a high-frequency event. We also present data concerning the amounts of unintegrated viral DNA found after the separare and mixed infections. There was no simple correlation between the amounts of unintegrated viral DNA early after infection and the titers of virus produced, indicating perhaps that virus production was determined by integrated viral DNA.", "contents": "Suppression of multiplication of avian sarcoma virus by rapid spread of transformation-defective virus of the same subgroup. We have tested the hypothesis that some transformation-defective (td) viruses grow faster than the avian sarcoma viruses (ASV) from which they are derived, resulting in establishment of interference by the td virus and suppression of the ASV multiplication. Using an ASV of subgroup A (ASV-A) that does not contain td virus and an independently isolated tdASV-A, we performed separate and mixed infections to test this hypothesis. At multiplicities of 1 or less, tdASV alone grew to higher titers and more rapidly than ASV alone. In mixed infections at low multiplicities that allowed spread of progeny virus, when as little as 10% of the virus inoculum was td virus, there was an excess of td virus by 2 days after infection and a decrease in the titer of ASV relative to a control infection with no td virus. In mixed infections at high multiplicities which minimized spread of progeny virus, there was no excess of td virus and the titer of ASV was not decreased relative to the control infection with no td virus. These data support the hypothesis that we proposed and indicate that deletions in the ASV src gene may not be a high-frequency event. We also present data concerning the amounts of unintegrated viral DNA found after the separare and mixed infections. There was no simple correlation between the amounts of unintegrated viral DNA early after infection and the titers of virus produced, indicating perhaps that virus production was determined by integrated viral DNA."}
{"id": "PMID:225562", "title": "Production of plasminogen activator by human and hamster cells infected with human cytomegalovirus.", "content": "Plasminogen activator was produced by both human embryo fibroblasts (a permissive system) and hamster embryo fibroblasts (a nonpermissive system) after exposure to human cytomegalovirus. The level of this activator was measured by using plates coated with [125I]fibrin. The production of plasminogen activator was enhanced when the human cells were exposed to human cytomegalovirus previously irradiated with UV light (5,520 to 55,200 ergs/mm2).", "contents": "Production of plasminogen activator by human and hamster cells infected with human cytomegalovirus. Plasminogen activator was produced by both human embryo fibroblasts (a permissive system) and hamster embryo fibroblasts (a nonpermissive system) after exposure to human cytomegalovirus. The level of this activator was measured by using plates coated with [125I]fibrin. The production of plasminogen activator was enhanced when the human cells were exposed to human cytomegalovirus previously irradiated with UV light (5,520 to 55,200 ergs/mm2)."}
{"id": "PMID:225563", "title": "Gs, an allele of chickens for endogenous avian leukosis viral antigens, segregates with ev 3, a genetic locus that contains structural genes for virus.", "content": "Gs is an allele of chickens for the expression of endogenous avian leukosis virus-related core (gs) and envelope (chf) antigens. Progeny of a genetic cross in which Gs was segregating were analyzed for endogenous viral DNA as well as for the expression of endogenous viral antigens. Viral genetic information was identified by cleavage of embryo DNA with restriction endonucleases, electrophoretic separation of the resulting fragments, and identification of bands containing viral sequences by hybridization of the DNA to 32P-labeled viral RNA. Four different chromosomal sites of residence of endogenous viral sequences were identified by this method. These sites were the same as those previously assigned to the endogenous viral loci ev 1, ev 3, ev 4, and ev 5. ev 1 was present in all of the progeny of the cross. ev 3, ev 4, and ev5 were present in various combinations with ev 1. ev 3 cosegregated with the gs+chf+ phenotpye. Cells which did not contain ev 3 but contained ev 1, ev 4, and/or ev 5, did not express detectable levels of viral antigens. We suggest that Gs contains the structural genes for endogenous virus which reside at ev 3 and that these structural genes code for gs and chf in gs+chf+ cells.", "contents": "Gs, an allele of chickens for endogenous avian leukosis viral antigens, segregates with ev 3, a genetic locus that contains structural genes for virus. Gs is an allele of chickens for the expression of endogenous avian leukosis virus-related core (gs) and envelope (chf) antigens. Progeny of a genetic cross in which Gs was segregating were analyzed for endogenous viral DNA as well as for the expression of endogenous viral antigens. Viral genetic information was identified by cleavage of embryo DNA with restriction endonucleases, electrophoretic separation of the resulting fragments, and identification of bands containing viral sequences by hybridization of the DNA to 32P-labeled viral RNA. Four different chromosomal sites of residence of endogenous viral sequences were identified by this method. These sites were the same as those previously assigned to the endogenous viral loci ev 1, ev 3, ev 4, and ev 5. ev 1 was present in all of the progeny of the cross. ev 3, ev 4, and ev5 were present in various combinations with ev 1. ev 3 cosegregated with the gs+chf+ phenotpye. Cells which did not contain ev 3 but contained ev 1, ev 4, and/or ev 5, did not express detectable levels of viral antigens. We suggest that Gs contains the structural genes for endogenous virus which reside at ev 3 and that these structural genes code for gs and chf in gs+chf+ cells."}
{"id": "PMID:225564", "title": "Isolation and localization of herpes simplex virus type 1 mRNA abundant before viral DNA synthesis.", "content": "Herpes simplex virus type 1 (HSV-1) DNA covalently bound to cellulose was used as a reagent to isolate viral RNA transcripts for size analysis on denaturing agarose gels. Nuclear and polyribosomal RNA isolated at 2 h postinfection (p.i.) migrated with sizes between 1,500 and 5,500 nucleotides. At 6 h p.i. (when viral DNA synthesis is underway), viral polyribosome-associated polyadenylated RNA showed different discrete sizes of species predominating, with RNA larger than 5,500 nucleotides clearly present. Nearly 50% of the newly made viral RNA found in the nucleus at 6 h p.i. was from 5,000 to 10,000 nucleotides in length. A high-resolution transcription map of the viral mRNA abundant at 2 h p.i. was compiled from the hybridization of Southern blots of HSV-1 DNA restriction fragments to both sizes of fractionated polyribosomal polyadenylated RNA and 3' complementary DNA probe made to this size of fractionated RNA. We have identified and mapped 16 mRNA species abundant at 2 h p.i. These RNAs range in size from 1,500 to 5,300 nucleotides and map throughout the HSV-1 genome. In some instances, a direction of transcription can be suggested. Further, about one-third of this number of mRNA's has been found in cells infected with a DNA-negative temperature-sensitive mutant (tsB2) and grown at the nonpermissive temperature (39 degrees C).", "contents": "Isolation and localization of herpes simplex virus type 1 mRNA abundant before viral DNA synthesis. Herpes simplex virus type 1 (HSV-1) DNA covalently bound to cellulose was used as a reagent to isolate viral RNA transcripts for size analysis on denaturing agarose gels. Nuclear and polyribosomal RNA isolated at 2 h postinfection (p.i.) migrated with sizes between 1,500 and 5,500 nucleotides. At 6 h p.i. (when viral DNA synthesis is underway), viral polyribosome-associated polyadenylated RNA showed different discrete sizes of species predominating, with RNA larger than 5,500 nucleotides clearly present. Nearly 50% of the newly made viral RNA found in the nucleus at 6 h p.i. was from 5,000 to 10,000 nucleotides in length. A high-resolution transcription map of the viral mRNA abundant at 2 h p.i. was compiled from the hybridization of Southern blots of HSV-1 DNA restriction fragments to both sizes of fractionated polyribosomal polyadenylated RNA and 3' complementary DNA probe made to this size of fractionated RNA. We have identified and mapped 16 mRNA species abundant at 2 h p.i. These RNAs range in size from 1,500 to 5,300 nucleotides and map throughout the HSV-1 genome. In some instances, a direction of transcription can be suggested. Further, about one-third of this number of mRNA's has been found in cells infected with a DNA-negative temperature-sensitive mutant (tsB2) and grown at the nonpermissive temperature (39 degrees C)."}
{"id": "PMID:225565", "title": "Identification and partial characterization of new antigens from simian virus 40-transformed mouse cells.", "content": "Two new species of antigens were detected in simian virus 40-transformed mouse cells, in addition to the large (94,000 daltons) and small (20,000 daltons) tumor antigens. These antigens were immunoprecipitated from cell extracts by using anti-T serum and not normal, nonimmune serum. One of these was a protein with a molecular weight of approximately 130,000 and was present in some but not all SV40-transformed mouse cells. The other, which we have named Tau antigen, has a molecular weight of 56,000 as estimated by electrophoresis through acrylamide gels and was found in all virus-transformed cells examined. The 13,000-daltons antigen contained about 15 methionine-tryptic peptides which were also present in the large SV40 tumor antigen as determined by ion-exchange chromatography. This strongly suggested that the protein was virus coded. The 56,000-dalton Tau antigen appeared to share only two methionine-tryptic peptides with the large species of SV40 tumor antigen, as determined by ion-exchange and paper chromatographies. Our results are compatible with a cellular origin for Tau antigen. However, our data do not exclude the possibility that this protein contains sequences specified by the virus DNA.", "contents": "Identification and partial characterization of new antigens from simian virus 40-transformed mouse cells. Two new species of antigens were detected in simian virus 40-transformed mouse cells, in addition to the large (94,000 daltons) and small (20,000 daltons) tumor antigens. These antigens were immunoprecipitated from cell extracts by using anti-T serum and not normal, nonimmune serum. One of these was a protein with a molecular weight of approximately 130,000 and was present in some but not all SV40-transformed mouse cells. The other, which we have named Tau antigen, has a molecular weight of 56,000 as estimated by electrophoresis through acrylamide gels and was found in all virus-transformed cells examined. The 13,000-daltons antigen contained about 15 methionine-tryptic peptides which were also present in the large SV40 tumor antigen as determined by ion-exchange chromatography. This strongly suggested that the protein was virus coded. The 56,000-dalton Tau antigen appeared to share only two methionine-tryptic peptides with the large species of SV40 tumor antigen, as determined by ion-exchange and paper chromatographies. Our results are compatible with a cellular origin for Tau antigen. However, our data do not exclude the possibility that this protein contains sequences specified by the virus DNA."}
{"id": "PMID:225566", "title": "Simian virus 40-transformed cells express new species of proteins precipitable by anti-simian virus 40 tumor serum.", "content": "In addition to the virus-coded large-T and small-t antigens, two new classes of proteins were immunoprecipitated by anti-simian virus 40 (SV40) tumor serum from extracts of various SV40-transformed cell lines. These were as follows: (i) proteins (termed \"super-T proteins\") with an Mr higher than that of large-T antigen (86,000), which were found in many SV40-transformed cell lines derived from mouse and rat cells (super-T proteins and large-T antigen appeared to have closely related structures as judged by the Chromobead elution patterns of their methionine-labeled tryptic peptides); (ii) proteins (termed \"55K proteins\") with an Mr ranging from 50,000 to 60,000, which were present in all SV40-transformed cell lines examined so far, including those obtained by chromosome-mediated gene transfer. The 55K proteins were not structurally related to large-T antigens, as judged by the Chromobead elution patterns of their methionine-labeled tryptic peptides. Our data are compatible with the assumption that the 55K proteins are largely or totally cell coded.", "contents": "Simian virus 40-transformed cells express new species of proteins precipitable by anti-simian virus 40 tumor serum. In addition to the virus-coded large-T and small-t antigens, two new classes of proteins were immunoprecipitated by anti-simian virus 40 (SV40) tumor serum from extracts of various SV40-transformed cell lines. These were as follows: (i) proteins (termed \"super-T proteins\") with an Mr higher than that of large-T antigen (86,000), which were found in many SV40-transformed cell lines derived from mouse and rat cells (super-T proteins and large-T antigen appeared to have closely related structures as judged by the Chromobead elution patterns of their methionine-labeled tryptic peptides); (ii) proteins (termed \"55K proteins\") with an Mr ranging from 50,000 to 60,000, which were present in all SV40-transformed cell lines examined so far, including those obtained by chromosome-mediated gene transfer. The 55K proteins were not structurally related to large-T antigens, as judged by the Chromobead elution patterns of their methionine-labeled tryptic peptides. Our data are compatible with the assumption that the 55K proteins are largely or totally cell coded."}
{"id": "PMID:225567", "title": "Heterogeneity of the 5' terminus of late mRNA induced by a viable simian virus 40 deletion mutant.", "content": "d1-1811 is a viable simian virus 40 deletion mutant which lacks the DNA region corresponding to the major capping site of the late viral RNA. The exact size of the deletion (40 base pairs) was determined by comparison of the mutant DNA sequence with the wild-type simian virus 40 (strain 776) DNA sequence. Although d1-1811 forms somewhat smaller plaques, the amount of viral RNA late after infection was not significantly reduced compared with that of the wild type. Virus-specific, polyadenylate-containing, 32P-labeled late RNA was purified from the cytoplasm and enzymatically degraded to characterize the 5' terminus. The cap-containing oligonucleotides were isolated, and their structures were analyzed by further digestion. Instead of a single cap structure, we found a variety of capped 5' termini, with adenosine caps occurring much more frequently than guanosine caps. Nevertheless, there was a remarkable homology between both types of terminal sequences. Conceivably, the minor cap population present in wild-type simian virus 40 late mRNA may correspond to the collection of capped termini identified in the d1-1811 late mRNA . Cellular cytoplasmic RNA shows a similar pattern of cap structures, but the relative abundance is quite different.", "contents": "Heterogeneity of the 5' terminus of late mRNA induced by a viable simian virus 40 deletion mutant. d1-1811 is a viable simian virus 40 deletion mutant which lacks the DNA region corresponding to the major capping site of the late viral RNA. The exact size of the deletion (40 base pairs) was determined by comparison of the mutant DNA sequence with the wild-type simian virus 40 (strain 776) DNA sequence. Although d1-1811 forms somewhat smaller plaques, the amount of viral RNA late after infection was not significantly reduced compared with that of the wild type. Virus-specific, polyadenylate-containing, 32P-labeled late RNA was purified from the cytoplasm and enzymatically degraded to characterize the 5' terminus. The cap-containing oligonucleotides were isolated, and their structures were analyzed by further digestion. Instead of a single cap structure, we found a variety of capped 5' termini, with adenosine caps occurring much more frequently than guanosine caps. Nevertheless, there was a remarkable homology between both types of terminal sequences. Conceivably, the minor cap population present in wild-type simian virus 40 late mRNA may correspond to the collection of capped termini identified in the d1-1811 late mRNA . Cellular cytoplasmic RNA shows a similar pattern of cap structures, but the relative abundance is quite different."}
{"id": "PMID:225568", "title": "Further characterization of the replicative complex of vesicular stomatitis virus.", "content": "Replicating vesicular stomatitis virus ribonucleoprotein (RNP) complexes were isolated in nonequilibrium Renografin density gradients. These nascent RNPs had the same buoyant density as virion nucleocapsids in both isopycnic Renografin and CsCl gradients. Both transcribing and replicating RNP complexes were shown to be stable in sucrose gradients, whereas only replicating RNP complexes were stable in Renografin gradients. Size analysis of the 5-min-pulse-labeled RNA species from the replicating RNPs using methylmercury gels revealed that the nascent strands were primarily less than full-length molecules. Longer times of radiolabeling demonstrated that the nascent RNA accumulated as 42S RNA, which was primarily of the same sense as the virion strand when it was radiolabeled at 5 h postinfection. The percentage of this radiolabeled RNA which was plus stranded was higher at 2.5 h postinfection, reflective of the shift in plus- to minus-stranded full-length 42S RNA synthesis which occurs in the cell. Addition of cycloheximide to the infected cells before the addition of the radiolabel prevented the formation of these RNP complexes. Both the change in the percentage of minus strands found in the RNP complexes at the different times postinfection and the sensitivity to cycloheximide indicate that the RNP complex which was isolated was indeed the replicative complex.", "contents": "Further characterization of the replicative complex of vesicular stomatitis virus. Replicating vesicular stomatitis virus ribonucleoprotein (RNP) complexes were isolated in nonequilibrium Renografin density gradients. These nascent RNPs had the same buoyant density as virion nucleocapsids in both isopycnic Renografin and CsCl gradients. Both transcribing and replicating RNP complexes were shown to be stable in sucrose gradients, whereas only replicating RNP complexes were stable in Renografin gradients. Size analysis of the 5-min-pulse-labeled RNA species from the replicating RNPs using methylmercury gels revealed that the nascent strands were primarily less than full-length molecules. Longer times of radiolabeling demonstrated that the nascent RNA accumulated as 42S RNA, which was primarily of the same sense as the virion strand when it was radiolabeled at 5 h postinfection. The percentage of this radiolabeled RNA which was plus stranded was higher at 2.5 h postinfection, reflective of the shift in plus- to minus-stranded full-length 42S RNA synthesis which occurs in the cell. Addition of cycloheximide to the infected cells before the addition of the radiolabel prevented the formation of these RNP complexes. Both the change in the percentage of minus strands found in the RNP complexes at the different times postinfection and the sensitivity to cycloheximide indicate that the RNP complex which was isolated was indeed the replicative complex."}
{"id": "PMID:225569", "title": "DNA and RNA from uninfected vertebrate cells contain nucleotide sequences related to the putative transforming gene of avian myelocytomatosis virus.", "content": "The avian carcinoma virus MC29 (MC29V) contains a sequence of approximately 1,500 nucleotides which may represent a gene responsible for tumorigenesis by MC29V. We present evidence that MC29V has acquired this nucleotide sequence from the DNA of its host. The host sequence which has been incorporated by MC29V is transcribed into RNA in uninfected chicken cells and thus probably encodes a cellular gene. We have prepared radioactive DNA complementary to the putative MC29V transforming gene (cDNA(mc) (29)) and have found that sequences homologous to cDNA(mc) (29) are present in the genomes of several uninfected vertebrate species. The DNA of chicken, the natural host for MC29V, contains at least 90% of the sequences represented by cDNA(mc) (29). DNAs from other animals show significant but decreasing amounts of complementarity to cDNA(mc) (29) in accordance with their evolutionary divergence from chickens; the thermal stabilities of duplexes formed between cDNA(mc) (29) and avian DNAs also reflect phylogenetic divergence. Sequences complementary to cDNA(mc) (29) are transcribed into approximately 10 copies per cell of polyadenylated RNA in uninfected chicken fibroblasts. Thus, the vertebrate homolog of cDNA(mc) (29) may be a gene which has been conserved throughout vertebrate evolution and which served as a progenitor for the putative transforming gene of MC29V. Recent experiments suggest that the putative transforming gene of avian erythroblastosis virus, like that of MC29V, may have arisen by incorporation of a host gene (Stehelin et al., personal communication). These findings for avian erythroblastosis virus and MC29V closely parallel previous results, suggesting a host origin for src (D. H. Spector, B. Baker, H. E. Varmus, and J. M. Bishop, Cell 13:381-386, 1978; D. H. Spector, K. Smith, T. Padgett, P. McCombe, D. Roulland-Dussoix, C. Moscovici, H. E. Varmus, and J. M. Bishop, Cell 13:371-379, 1978; D. H. Spector, H. E. Varmus, and J. M. Bishop, Proc. Natl. Acad. Sci. U.S.A. 75:4102-4106, 1978; D. Stehelin, H. E. Varmus, J. M. Bishop, and P. K. Vogt, Nature [London] 260:170-173, 1976), the gene responsible for tumorigenesis by avian sarcoma virus. Avian sarcoma virus, avian erythroblastosis virus, and MC29V, however, induce distinctly different spectra of tumors within their host. The putative transforming genes of these viruses share no detectable homology, although sequences homologous to all three types of putative transforming genes occur and are highly conserved in the genomes of several vertebrate species. These data suggest that evolution of oncogenic retroviruses has frequently involved a mechanism whereby incorporation and perhaps modification of different host genes provides each virus with the ability to induce its characteristic tumors.", "contents": "DNA and RNA from uninfected vertebrate cells contain nucleotide sequences related to the putative transforming gene of avian myelocytomatosis virus. The avian carcinoma virus MC29 (MC29V) contains a sequence of approximately 1,500 nucleotides which may represent a gene responsible for tumorigenesis by MC29V. We present evidence that MC29V has acquired this nucleotide sequence from the DNA of its host. The host sequence which has been incorporated by MC29V is transcribed into RNA in uninfected chicken cells and thus probably encodes a cellular gene. We have prepared radioactive DNA complementary to the putative MC29V transforming gene (cDNA(mc) (29)) and have found that sequences homologous to cDNA(mc) (29) are present in the genomes of several uninfected vertebrate species. The DNA of chicken, the natural host for MC29V, contains at least 90% of the sequences represented by cDNA(mc) (29). DNAs from other animals show significant but decreasing amounts of complementarity to cDNA(mc) (29) in accordance with their evolutionary divergence from chickens; the thermal stabilities of duplexes formed between cDNA(mc) (29) and avian DNAs also reflect phylogenetic divergence. Sequences complementary to cDNA(mc) (29) are transcribed into approximately 10 copies per cell of polyadenylated RNA in uninfected chicken fibroblasts. Thus, the vertebrate homolog of cDNA(mc) (29) may be a gene which has been conserved throughout vertebrate evolution and which served as a progenitor for the putative transforming gene of MC29V. Recent experiments suggest that the putative transforming gene of avian erythroblastosis virus, like that of MC29V, may have arisen by incorporation of a host gene (Stehelin et al., personal communication). These findings for avian erythroblastosis virus and MC29V closely parallel previous results, suggesting a host origin for src (D. H. Spector, B. Baker, H. E. Varmus, and J. M. Bishop, Cell 13:381-386, 1978; D. H. Spector, K. Smith, T. Padgett, P. McCombe, D. Roulland-Dussoix, C. Moscovici, H. E. Varmus, and J. M. Bishop, Cell 13:371-379, 1978; D. H. Spector, H. E. Varmus, and J. M. Bishop, Proc. Natl. Acad. Sci. U.S.A. 75:4102-4106, 1978; D. Stehelin, H. E. Varmus, J. M. Bishop, and P. K. Vogt, Nature [London] 260:170-173, 1976), the gene responsible for tumorigenesis by avian sarcoma virus. Avian sarcoma virus, avian erythroblastosis virus, and MC29V, however, induce distinctly different spectra of tumors within their host. The putative transforming genes of these viruses share no detectable homology, although sequences homologous to all three types of putative transforming genes occur and are highly conserved in the genomes of several vertebrate species. These data suggest that evolution of oncogenic retroviruses has frequently involved a mechanism whereby incorporation and perhaps modification of different host genes provides each virus with the ability to induce its characteristic tumors."}
{"id": "PMID:225570", "title": "p21 of Kirsten murine sarcoma virus is thermolabile in a viral mutant temperature sensitive for the maintenance of transformation.", "content": "We have recently described an intracellular protein, p21, in nonproducer cells transformed by either the Kirsten (Ki-MSV) or Harvey (Ha-MSV) strain of murine sarcoma virus (Shih et al., Virology, in press). The p21 is phosphorylated and has been shown to be coded for by either Ki-MSV or Ha-MSV. In this report, we compare the thermal stability of the newly synthesized [35S]methionine-labeled p21 in cells transformed by the wild-type Ki-MSV or by a mutant of Ki-MSV (ts 371) which is temperature sensitive in a viral function required for the maintenance of several properties of the transformed phenotype. The immunoprecipitability of the p21 coded for by the ts 371 Ki-MSV was markedly more thermolabile than the p21 of the wild-type Ki-MSV when the cell extracts are heated in vitro. The present finding suggests that the p21 is required for the maintenance of transformation induced by Ki-MSV.", "contents": "p21 of Kirsten murine sarcoma virus is thermolabile in a viral mutant temperature sensitive for the maintenance of transformation. We have recently described an intracellular protein, p21, in nonproducer cells transformed by either the Kirsten (Ki-MSV) or Harvey (Ha-MSV) strain of murine sarcoma virus (Shih et al., Virology, in press). The p21 is phosphorylated and has been shown to be coded for by either Ki-MSV or Ha-MSV. In this report, we compare the thermal stability of the newly synthesized [35S]methionine-labeled p21 in cells transformed by the wild-type Ki-MSV or by a mutant of Ki-MSV (ts 371) which is temperature sensitive in a viral function required for the maintenance of several properties of the transformed phenotype. The immunoprecipitability of the p21 coded for by the ts 371 Ki-MSV was markedly more thermolabile than the p21 of the wild-type Ki-MSV when the cell extracts are heated in vitro. The present finding suggests that the p21 is required for the maintenance of transformation induced by Ki-MSV."}
{"id": "PMID:225571", "title": "Method for determining the extent and copy number of overlapping and nonoverlapping segments of integrated viral genomes.", "content": "We analyzed the method of exhaustive hybridization of single-stranded DNA and derived a general relationship between the fraction of the probe DNA hybridized and the sizes and copy numbers of the segments of the viral genome integrated in cellular DNA. The equations employed can be used to analyze integrated DNA comprised of overlapping and nonoverlapping segments of the viral genome. Using these equations, we analyzd the adenovirus type 2 DNA content of a series of hamster cell lines transformed by adenovirus type 2 and several adenovirus type 2-simian virus 40 hybrid viruses. We found no eividence that the integrated viral DNA is comprised of overlapsping segments. However, the number of copies of the integrated segments varies between lines cloned from the same transformed isolate, and copy numbers change during in vivo passage of transformed cells.", "contents": "Method for determining the extent and copy number of overlapping and nonoverlapping segments of integrated viral genomes. We analyzed the method of exhaustive hybridization of single-stranded DNA and derived a general relationship between the fraction of the probe DNA hybridized and the sizes and copy numbers of the segments of the viral genome integrated in cellular DNA. The equations employed can be used to analyze integrated DNA comprised of overlapping and nonoverlapping segments of the viral genome. Using these equations, we analyzd the adenovirus type 2 DNA content of a series of hamster cell lines transformed by adenovirus type 2 and several adenovirus type 2-simian virus 40 hybrid viruses. We found no eividence that the integrated viral DNA is comprised of overlapsping segments. However, the number of copies of the integrated segments varies between lines cloned from the same transformed isolate, and copy numbers change during in vivo passage of transformed cells."}
{"id": "PMID:225572", "title": "Cystic nephroma: an ultrastructural and biochemical study.", "content": "A case of a multilocular renal cyst (cystic nephroma) in an 18-month-girl is presented. The light and electron microscopy studies failed to demonstrate nephroblastomatous elements. Analysis of cystic fluid constituents showed levels resembling serum. Measurable levels of prostaglandins E and F also were found. The possible relationship of a cystic nephroma to a nephroblastoma is discussed.", "contents": "Cystic nephroma: an ultrastructural and biochemical study. A case of a multilocular renal cyst (cystic nephroma) in an 18-month-girl is presented. The light and electron microscopy studies failed to demonstrate nephroblastomatous elements. Analysis of cystic fluid constituents showed levels resembling serum. Measurable levels of prostaglandins E and F also were found. The possible relationship of a cystic nephroma to a nephroblastoma is discussed."}
{"id": "PMID:225574", "title": "Embryonal nephroma in a wapiti.", "content": "Ebryonal nephroma was diagnosed in a young, free-ranging female wapiti (Cervus canadensis) from the San Juan National Forest in southwestern Colorado. Metastases were found in the lung.", "contents": "Embryonal nephroma in a wapiti. Ebryonal nephroma was diagnosed in a young, free-ranging female wapiti (Cervus canadensis) from the San Juan National Forest in southwestern Colorado. Metastases were found in the lung."}
{"id": "PMID:225575", "title": "Antigenic comparisons between herpesviruses isolated from fallow deer in Alberta and the viruses of infectious bovine rhinotracheitis, equine rhinopneumonitis and DN-599, a non-IBR bovine herpesvirus.", "content": "Antigenic comparison studies of three herpesviruses isolated from fallow deer (Dama dama) in Alberta and herpesviruses from some domestic species were carried out by the alpha serum-virus neutralization test. Complete cross neutralization was demonstrated among the deer herpesviruses and equine herpesvirus type 1.", "contents": "Antigenic comparisons between herpesviruses isolated from fallow deer in Alberta and the viruses of infectious bovine rhinotracheitis, equine rhinopneumonitis and DN-599, a non-IBR bovine herpesvirus. Antigenic comparison studies of three herpesviruses isolated from fallow deer (Dama dama) in Alberta and herpesviruses from some domestic species were carried out by the alpha serum-virus neutralization test. Complete cross neutralization was demonstrated among the deer herpesviruses and equine herpesvirus type 1."}
{"id": "PMID:225582", "title": "Effects of beer, wine, and liquor in coronary deaths.", "content": "For a series of 568 married men who died of coronary heart disease and an equal number of matched control subjects, information was collected on a large number of variables, including daily alcohol consumption classified by type of beverage, namely, beer, wine, or liquor. Daily consumption of small to moderate amounts of alcohol (2 oz [59.2mL] or less daily) was inversely related to coronary death. This inverse relation was present in both crude and adjusted matched-pair analyses and was similar for each type of alcohol, as indicated by adjusted relative risks of 0.3 for beer, 0.3 for wine, and 0.2 for liquor. In contrast, for heavy drinking, there was no association with coronary death in either crude or adjusted analyses.", "contents": "Effects of beer, wine, and liquor in coronary deaths. For a series of 568 married men who died of coronary heart disease and an equal number of matched control subjects, information was collected on a large number of variables, including daily alcohol consumption classified by type of beverage, namely, beer, wine, or liquor. Daily consumption of small to moderate amounts of alcohol (2 oz [59.2mL] or less daily) was inversely related to coronary death. This inverse relation was present in both crude and adjusted matched-pair analyses and was similar for each type of alcohol, as indicated by adjusted relative risks of 0.3 for beer, 0.3 for wine, and 0.2 for liquor. In contrast, for heavy drinking, there was no association with coronary death in either crude or adjusted analyses."}
{"id": "PMID:225592", "title": "Response of athymic nude mice to Sendai virus.", "content": "Athymic nude mice and euthymic litter mates with BALB/cA back-ground were infected intranasally with a strain of Sendai virus. While no severe illness occurred in euthymic litter mates, some of nude mice showed marked body weight loss and died within 3 weeks after infection. The remaining nude mice recovered from the early depression and survived for 6 weeks or more with chronic pulmonary lesions. The virus was demonstrable in lungs of these chronic cases up to 10 weeks after infection, and none of infected nude mice were found to have anti-Sendai virus antibodies. Pulmonary lesions were characterized by diffuse interstitial pneumonia with a high incidence of prominent adenomatous metaplasia of alveolar epithelium.", "contents": "Response of athymic nude mice to Sendai virus. Athymic nude mice and euthymic litter mates with BALB/cA back-ground were infected intranasally with a strain of Sendai virus. While no severe illness occurred in euthymic litter mates, some of nude mice showed marked body weight loss and died within 3 weeks after infection. The remaining nude mice recovered from the early depression and survived for 6 weeks or more with chronic pulmonary lesions. The virus was demonstrable in lungs of these chronic cases up to 10 weeks after infection, and none of infected nude mice were found to have anti-Sendai virus antibodies. Pulmonary lesions were characterized by diffuse interstitial pneumonia with a high incidence of prominent adenomatous metaplasia of alveolar epithelium."}
{"id": "PMID:225597", "title": "Action of serotonin (5-hydroxytryptamine) on cyclic nucleotides in glomeruli of rat renal cortex.", "content": "Serotonin (5-hydroxytryptamine) is known to influence glomerular function and may have an important role in the pathogenesis of glomerulopathies. Because serotonin acts in nonrenal tissues through mediation of cyclic nucleotides, we investigated in vitro its effect on cAMP and cyclic guanosine monophasphate (cGMP) in tissue slices and isolated glomeruli from rat kidney. Serotonin increased cAMP 161 +/- 35% but not cGMP in renal cortex; it had no effect on cyclic nucleotides in medulla and papilla. In isolated glomeruli, serotonin elicited a dose-dependent (in the range of 10-7 to 10-4 M) increase in cAMP; the maximum increase over basal values was 376 +/- 45%. Serotonin increased cAMP either in the presence or in the absence of a cAMP phosphodiesterase inhibitor. In tubular fraction, serotonin elevated cAMP to a much lesser degree (82 +/- 15%). Neither in glomeruli nor in tubules did cGMP concentrations change in response to serotonin, but carbamylcholine, a known cGMP agonist, significantly increased cGMP concentrations. The increase in cAMP in response to serotonin was blocked (greater than 85% inhibition) by equimolar concentrations of serotonin antagonists methysergide and cinanserine. Results of this study demonstrate that interaction of serotonin with receptors in the kidney, particularly in the glomeruli, cause a striking increase in cAMP concentrations without detectable changes in cGMP concentrations. These findings suggest that serotonin, either synthesized in the kidney or released locally from platelets aggregated in glomeruli (for example, in association with immunopathologic injury) may exert of modulate its physiologic or pathologic effects via mediation of cAMP.", "contents": "Action of serotonin (5-hydroxytryptamine) on cyclic nucleotides in glomeruli of rat renal cortex. Serotonin (5-hydroxytryptamine) is known to influence glomerular function and may have an important role in the pathogenesis of glomerulopathies. Because serotonin acts in nonrenal tissues through mediation of cyclic nucleotides, we investigated in vitro its effect on cAMP and cyclic guanosine monophasphate (cGMP) in tissue slices and isolated glomeruli from rat kidney. Serotonin increased cAMP 161 +/- 35% but not cGMP in renal cortex; it had no effect on cyclic nucleotides in medulla and papilla. In isolated glomeruli, serotonin elicited a dose-dependent (in the range of 10-7 to 10-4 M) increase in cAMP; the maximum increase over basal values was 376 +/- 45%. Serotonin increased cAMP either in the presence or in the absence of a cAMP phosphodiesterase inhibitor. In tubular fraction, serotonin elevated cAMP to a much lesser degree (82 +/- 15%). Neither in glomeruli nor in tubules did cGMP concentrations change in response to serotonin, but carbamylcholine, a known cGMP agonist, significantly increased cGMP concentrations. The increase in cAMP in response to serotonin was blocked (greater than 85% inhibition) by equimolar concentrations of serotonin antagonists methysergide and cinanserine. Results of this study demonstrate that interaction of serotonin with receptors in the kidney, particularly in the glomeruli, cause a striking increase in cAMP concentrations without detectable changes in cGMP concentrations. These findings suggest that serotonin, either synthesized in the kidney or released locally from platelets aggregated in glomeruli (for example, in association with immunopathologic injury) may exert of modulate its physiologic or pathologic effects via mediation of cAMP."}
{"id": "PMID:225599", "title": "[Rotavirus diarrhea in childhood].", "content": "Electron microscopy of 350 diarrhoeal faeces revealed Rotavirus-particles in 145 cases. All patients with Rotavirus-infections showed symptoms of acute gastroenteritis lasting 1 to 8 days. Additionally to diarrhoea most cases presented fever and vomiting. None of the patients showed toxicosis.", "contents": "[Rotavirus diarrhea in childhood]. Electron microscopy of 350 diarrhoeal faeces revealed Rotavirus-particles in 145 cases. All patients with Rotavirus-infections showed symptoms of acute gastroenteritis lasting 1 to 8 days. Additionally to diarrhoea most cases presented fever and vomiting. None of the patients showed toxicosis."}
{"id": "PMID:225596", "title": "Postpartum follow-up goals and assessment.", "content": "The bridge between hospital and home in the puerperal period needs to be assessed for effective intervention, anticipatory guidance, and support in parenting careers. Through the development of specific goals, assessment criteria and cultural implications, the nurse practitioner can hopefully minimize the development crisis for the postpartal family unit.", "contents": "Postpartum follow-up goals and assessment. The bridge between hospital and home in the puerperal period needs to be assessed for effective intervention, anticipatory guidance, and support in parenting careers. Through the development of specific goals, assessment criteria and cultural implications, the nurse practitioner can hopefully minimize the development crisis for the postpartal family unit."}
{"id": "PMID:225602", "title": "[The value of an outpatient clinic for patients with retinal detachment].", "content": "The article reports on an outpatient department for retinal detachment patients established since 1972 in the First Eye Clinic in Vienna. Of the 225 patients treated up to 1978, 19 had a relapse, 9 patients were subjected to prophylactic retinopexy in the tear area which had not coagulated sufficiently, whereas in 15 cases latent tears were found in healed eyes and in 17 cases in the second eye. In two patients, beginning detachment in the second eye was detected at an early stage, whereas in two cases detachment occurred despite continual control. The article underlines the usefulness of this outpatient section for clinical and research work.", "contents": "[The value of an outpatient clinic for patients with retinal detachment]. The article reports on an outpatient department for retinal detachment patients established since 1972 in the First Eye Clinic in Vienna. Of the 225 patients treated up to 1978, 19 had a relapse, 9 patients were subjected to prophylactic retinopexy in the tear area which had not coagulated sufficiently, whereas in 15 cases latent tears were found in healed eyes and in 17 cases in the second eye. In two patients, beginning detachment in the second eye was detected at an early stage, whereas in two cases detachment occurred despite continual control. The article underlines the usefulness of this outpatient section for clinical and research work."}
{"id": "PMID:225603", "title": "[Computerized tomography in finding tumours in the orbit and in the base of the skull (author's transl)].", "content": "Two cases of tumours - a pleomorphic poorly differentiated malignant neoplasm and a juvenile angiofibroma - involving the orbit and extending to the base of the skull are reported. In both cases computerized tomography showed with great precision the localization and the extension of the tumours.", "contents": "[Computerized tomography in finding tumours in the orbit and in the base of the skull (author's transl)]. Two cases of tumours - a pleomorphic poorly differentiated malignant neoplasm and a juvenile angiofibroma - involving the orbit and extending to the base of the skull are reported. In both cases computerized tomography showed with great precision the localization and the extension of the tumours."}
{"id": "PMID:225605", "title": "Activities of urea-cycle enzymes in chronic liver disease.", "content": "The activities of urea-cycle enzymes were measured in liver biopsies of patients suffering from chronic-persistent hepatitis (CPH), chronic-active hepatitis (CAH) and liver cirrhosis. Most of the activities of urea-cycle enzymes did not differ in the case of CPH as compared to controls. Chronic-active hepatitis and liver cirrhosis are associated with a significant (p less than 0.05) decrease of enzyme activity as compared to normal persons. Most of the urea-cycle enzymes are significantly decreased in patients with CAH in comparison with CPH. No significant differences can be demonstrated in the case of CAH as compared to patients with complete cirrhosis. In conclusion, progression of chronic liver disease is associated with increasing alterations of enzyme activities catalyzing a liver specific metabolic pathway. The decrease of the activities of the key enzymes of the urea cycle (Carbamylphosphate-Synthetase and Arginino-succinate-Synthetase) is nearly identical both in CAH and liver cirhosis, although CAH may be a reversible disease. Therefore, marked alterations in the metabolic pathway of ammonia detoxification seem to preceed the histological manifestation of irreversible liver damage.", "contents": "Activities of urea-cycle enzymes in chronic liver disease. The activities of urea-cycle enzymes were measured in liver biopsies of patients suffering from chronic-persistent hepatitis (CPH), chronic-active hepatitis (CAH) and liver cirrhosis. Most of the activities of urea-cycle enzymes did not differ in the case of CPH as compared to controls. Chronic-active hepatitis and liver cirrhosis are associated with a significant (p less than 0.05) decrease of enzyme activity as compared to normal persons. Most of the urea-cycle enzymes are significantly decreased in patients with CAH in comparison with CPH. No significant differences can be demonstrated in the case of CAH as compared to patients with complete cirrhosis. In conclusion, progression of chronic liver disease is associated with increasing alterations of enzyme activities catalyzing a liver specific metabolic pathway. The decrease of the activities of the key enzymes of the urea cycle (Carbamylphosphate-Synthetase and Arginino-succinate-Synthetase) is nearly identical both in CAH and liver cirhosis, although CAH may be a reversible disease. Therefore, marked alterations in the metabolic pathway of ammonia detoxification seem to preceed the histological manifestation of irreversible liver damage."}
{"id": "PMID:225606", "title": "Umbilical metastasis as the presenting symptom of cecal carcinoma.", "content": "Umbilical metastases were encountered as the initial presentation of cecal adenocarcinoma in a 62-year-old woman. Intravenous infusion of 5-fluorouracil, along with intralesional injections of 10% 5-fluorouracil, resulted in regression of the tumor masses on the abdominal wall. Although umbilical metastasis is rare, its significance in diagnosing an otherwise silent colorectal cancer warrants the physician's awareness.", "contents": "Umbilical metastasis as the presenting symptom of cecal carcinoma. Umbilical metastases were encountered as the initial presentation of cecal adenocarcinoma in a 62-year-old woman. Intravenous infusion of 5-fluorouracil, along with intralesional injections of 10% 5-fluorouracil, resulted in regression of the tumor masses on the abdominal wall. Although umbilical metastasis is rare, its significance in diagnosing an otherwise silent colorectal cancer warrants the physician's awareness."}
{"id": "PMID:225611", "title": "Giant cell tumor of the ethmoid sinuses: diagnostic dilemma.", "content": "Tumors originating in the ethmoid sinuses are rare. Carcinomas of the ethmoid sinus, for example, comprise only 2-3% of all head and neck malignancies. Of this small sample, the ethmoid sinuses as the primary site varies from 5-30%. This paper presents the 14th documented case of giant cell tumor originating in the ethmoid sinuses. The pathology became the diagnostic dilemma; the case was originally diagnosed as an angiofibroma, later a reparative granuloma, and finally accepted as a giant cell tumor. The rationale for diagnosis and therapy is discussed.", "contents": "Giant cell tumor of the ethmoid sinuses: diagnostic dilemma. Tumors originating in the ethmoid sinuses are rare. Carcinomas of the ethmoid sinus, for example, comprise only 2-3% of all head and neck malignancies. Of this small sample, the ethmoid sinuses as the primary site varies from 5-30%. This paper presents the 14th documented case of giant cell tumor originating in the ethmoid sinuses. The pathology became the diagnostic dilemma; the case was originally diagnosed as an angiofibroma, later a reparative granuloma, and finally accepted as a giant cell tumor. The rationale for diagnosis and therapy is discussed."}
{"id": "PMID:225612", "title": "[Diagnosis of liver and biliary diseases with 99mTc-Hepatobida (author's transl)].", "content": "Application of 99mTc-Hepatobida has turned out to be a convenient diagnostic screening method in liver and biliary disease. Side effects are unknown, thus patients with iodine allergy or other forms of allergy, as well as patients harboring autonomous adenomata of the thyroid, and severely ill patients will tolerate this substance well. 99mTc-Hepatobida may be applied even in the presence of highly elevated levels of plasma bilirubin and thus will yield diagnostic results in all forms of hepatic disease if findings are monitored repeatedly. In addition screening with 99mTc-Hepatobida will in some cases suffice to establish the diagnosis and thus forgo more complicated diagnostic procedures.", "contents": "[Diagnosis of liver and biliary diseases with 99mTc-Hepatobida (author's transl)]. Application of 99mTc-Hepatobida has turned out to be a convenient diagnostic screening method in liver and biliary disease. Side effects are unknown, thus patients with iodine allergy or other forms of allergy, as well as patients harboring autonomous adenomata of the thyroid, and severely ill patients will tolerate this substance well. 99mTc-Hepatobida may be applied even in the presence of highly elevated levels of plasma bilirubin and thus will yield diagnostic results in all forms of hepatic disease if findings are monitored repeatedly. In addition screening with 99mTc-Hepatobida will in some cases suffice to establish the diagnosis and thus forgo more complicated diagnostic procedures."}
{"id": "PMID:225633", "title": "Cholesteryl ester and triacylglycerol fatty acids in type V hyperlipidemia.", "content": "The fatty acid compositions of plasma cholesteryl esters (CF) and triacylglycerols (TG) from seven healthy individuals and five patients with type V hyperlipoproteinemia were determined. Very low density (VLDL), low density (LDL) and high density lipoproteins (HDL) wer isolated. The lipids were extracted from the lipoproteins and the triacylglycerols and cholesteryl esters separated for analysis. The fatty acid compositions of triacylglycerols from healthy and type V individuals were very similar. The cholesteryl esters from type V patients had increased contents of palmitic and decreased amounts of linoleic and arachidonic acids as compared to the normal individuals. The fatty acid composition of the cholesteryl esters from high density lipoproteins had the greatest deviation. The fatty acid compositions of the triacylglycerols from the two groups were similar. However, the triacylglycerols in all lipoprotein fractions contained more palmitic and oleic and less linoleic and arachidonic acids than the cholesteryl esters.", "contents": "Cholesteryl ester and triacylglycerol fatty acids in type V hyperlipidemia. The fatty acid compositions of plasma cholesteryl esters (CF) and triacylglycerols (TG) from seven healthy individuals and five patients with type V hyperlipoproteinemia were determined. Very low density (VLDL), low density (LDL) and high density lipoproteins (HDL) wer isolated. The lipids were extracted from the lipoproteins and the triacylglycerols and cholesteryl esters separated for analysis. The fatty acid compositions of triacylglycerols from healthy and type V individuals were very similar. The cholesteryl esters from type V patients had increased contents of palmitic and decreased amounts of linoleic and arachidonic acids as compared to the normal individuals. The fatty acid composition of the cholesteryl esters from high density lipoproteins had the greatest deviation. The fatty acid compositions of the triacylglycerols from the two groups were similar. However, the triacylglycerols in all lipoprotein fractions contained more palmitic and oleic and less linoleic and arachidonic acids than the cholesteryl esters."}
{"id": "PMID:225637", "title": "[Urinary lead concentration as a risk factor during mixed exposure to lead, zinc and cadmium].", "content": "Six groups of subjects with different exposure to lead, zinc and cadmium, selected from among workers of zinc works, were studied. The concentration of the metals in the air was in the range: 0.04--0.70 mg Pb/m3; 0.16--1.84 mg ZnO/m3 and below 0.020 mg CdO/m3. Urine specimens were taken several times from the same subjects in mid -- week between the 3rd and 5th work hour. The concentration of the metals in urine was determined by the atomic absorption spectrophotometric method. The exposure to the metals was based on the relation between their concentrations in the air and urine. Statistical analysis indicated that under the conditions of mixed exposure to lead, zinc and cadmium, lead concentration in urine -- with prevailing toxic effects of lead -- may be used to evaluate occupational exposure.", "contents": "[Urinary lead concentration as a risk factor during mixed exposure to lead, zinc and cadmium]. Six groups of subjects with different exposure to lead, zinc and cadmium, selected from among workers of zinc works, were studied. The concentration of the metals in the air was in the range: 0.04--0.70 mg Pb/m3; 0.16--1.84 mg ZnO/m3 and below 0.020 mg CdO/m3. Urine specimens were taken several times from the same subjects in mid -- week between the 3rd and 5th work hour. The concentration of the metals in urine was determined by the atomic absorption spectrophotometric method. The exposure to the metals was based on the relation between their concentrations in the air and urine. Statistical analysis indicated that under the conditions of mixed exposure to lead, zinc and cadmium, lead concentration in urine -- with prevailing toxic effects of lead -- may be used to evaluate occupational exposure."}
{"id": "PMID:225634", "title": "[Hepatitic amoebiasis (75 cases observed in Treichville University Hospital Abidjan--Ivory Coast) (author's transl)].", "content": "Reporting 75 original cases the authors review the clinical radiological and biological syndroma of hepatitic amoebiasis. They emphasize the recent advances in medical treatments which frequently give opportunity of avoiding surgery. But surgical intervention cannot be systematically discarded and has been necessary in 11 p. 100 of the reported cases. Drainage strengthens drugs efficiency. Antibiotherapy is generally useless.", "contents": "[Hepatitic amoebiasis (75 cases observed in Treichville University Hospital Abidjan--Ivory Coast) (author's transl)]. Reporting 75 original cases the authors review the clinical radiological and biological syndroma of hepatitic amoebiasis. They emphasize the recent advances in medical treatments which frequently give opportunity of avoiding surgery. But surgical intervention cannot be systematically discarded and has been necessary in 11 p. 100 of the reported cases. Drainage strengthens drugs efficiency. Antibiotherapy is generally useless."}
{"id": "PMID:225638", "title": "Cushing's syndrome: a review of diagnostic tests.", "content": "This review presents an analysis and interpretation of the published experimental data that form the basis for laboratory tests commonly used for screening, definitive diagnosis, and differential diagnosis in Cushing's syndrome. The single-dose overnight dexamethasone suppression test is excellent for screening outpatients since this test has a very low incidence of false-negative results (1.9% of 154 patients with Cushing's syndrome). The definitive diagnosis of Cushing's syndrome is best established by combining basal state measurements of the daily urine-free cortisol excretion and late evening plasma cortisol levels with the 2-mg low-dose dexamethasone suppression test. The etiology of Cushing's syndrome is best determined by combining measurements of basal state plasma adrenocorticotropin (ACTH) levels with the 8-mg high-dose dexamethasone suppression test. Under certain conditions, the basal state daily urine excretion of 17-hydroxycorticosteroids and 17-ketogenic steroids, the insulin tolerance test, and the metyrapone test may be useful in the definitive or differential diagnosis of Cushing's syndrome.", "contents": "Cushing's syndrome: a review of diagnostic tests. This review presents an analysis and interpretation of the published experimental data that form the basis for laboratory tests commonly used for screening, definitive diagnosis, and differential diagnosis in Cushing's syndrome. The single-dose overnight dexamethasone suppression test is excellent for screening outpatients since this test has a very low incidence of false-negative results (1.9% of 154 patients with Cushing's syndrome). The definitive diagnosis of Cushing's syndrome is best established by combining basal state measurements of the daily urine-free cortisol excretion and late evening plasma cortisol levels with the 2-mg low-dose dexamethasone suppression test. The etiology of Cushing's syndrome is best determined by combining measurements of basal state plasma adrenocorticotropin (ACTH) levels with the 8-mg high-dose dexamethasone suppression test. Under certain conditions, the basal state daily urine excretion of 17-hydroxycorticosteroids and 17-ketogenic steroids, the insulin tolerance test, and the metyrapone test may be useful in the definitive or differential diagnosis of Cushing's syndrome."}
{"id": "PMID:225635", "title": "[Ocular lesions in leprosy (author's transl)].", "content": "Modern authors estimate from 47 p. 100 to 78 p. 100 the frequency of ocular lesions in leprosy. This frequency varies according to the duration and type of the disease. These lesions may result from a paralysis of the V or VII cranial nerves, or from a bacteremia, but, more probably, from a spreading of the bacilli from the nasal cavity through the lacrymal ducts. The various lesions of each ocular structure are described with reference to the T. or L. type of leprosy.", "contents": "[Ocular lesions in leprosy (author's transl)]. Modern authors estimate from 47 p. 100 to 78 p. 100 the frequency of ocular lesions in leprosy. This frequency varies according to the duration and type of the disease. These lesions may result from a paralysis of the V or VII cranial nerves, or from a bacteremia, but, more probably, from a spreading of the bacilli from the nasal cavity through the lacrymal ducts. The various lesions of each ocular structure are described with reference to the T. or L. type of leprosy."}
{"id": "PMID:225636", "title": "[Distributions of Ascaris lumbricoides, Necator americanus and Trichuris trichiura in 6 villages of Ivory Coast (author's transl)].", "content": "Results of stool controls (Kato's technic) in 425 children from 7 to 14 years old in 6 villages of the south districts of Ivory Coast. Necator and Trichuris have a high prevalence (75 p. 100) versus 40 p. 100 for Ascaris-Trichuris is specially frequent in urban and suburban areas.", "contents": "[Distributions of Ascaris lumbricoides, Necator americanus and Trichuris trichiura in 6 villages of Ivory Coast (author's transl)]. Results of stool controls (Kato's technic) in 425 children from 7 to 14 years old in 6 villages of the south districts of Ivory Coast. Necator and Trichuris have a high prevalence (75 p. 100) versus 40 p. 100 for Ascaris-Trichuris is specially frequent in urban and suburban areas."}
{"id": "PMID:225640", "title": "A complementation analysis of mobilization deficient mutants of the plasmid ColE1.", "content": "Hydroxylamine was used to induce mutants of the ColE1 derived plasmid pML2 that are inefficiently mobilized (Mob-) during conjugation by an Hfr donor. The ability of those mutants to be complemented by deletion mutants and Tn3 insertion mutants of ColE1 was examined. Three complementation groups were identified and localized on the ColE1 genetic map (Mob1, Mob2, and Mob3). One hydroxylamine mutant was not complemented by any mobilization deficient mutant but was complemented by mobilizable ColE1 mutants. Two hydroxylamine mutants were not complemented by any ColE1 derivatives. A mutant that had its relaxation nick site deleted had a markedly reduced mobilizability. The relationship between DNA relaxation nick site deleted had a markedly reduced mobilizability. THe relationship between DNA relaxation, replication and mobilization is considered.", "contents": "A complementation analysis of mobilization deficient mutants of the plasmid ColE1. Hydroxylamine was used to induce mutants of the ColE1 derived plasmid pML2 that are inefficiently mobilized (Mob-) during conjugation by an Hfr donor. The ability of those mutants to be complemented by deletion mutants and Tn3 insertion mutants of ColE1 was examined. Three complementation groups were identified and localized on the ColE1 genetic map (Mob1, Mob2, and Mob3). One hydroxylamine mutant was not complemented by any mobilization deficient mutant but was complemented by mobilizable ColE1 mutants. Two hydroxylamine mutants were not complemented by any ColE1 derivatives. A mutant that had its relaxation nick site deleted had a markedly reduced mobilizability. The relationship between DNA relaxation nick site deleted had a markedly reduced mobilizability. THe relationship between DNA relaxation, replication and mobilization is considered."}
{"id": "PMID:225641", "title": "Expression of the lac operon in RNA polymerase mutants of Escherichia coli K12.", "content": "Three temperature-sensitive mutant strains for RNA polymerase beta or beta' subunits (carrying mutations tsx, A2R7 and R120) were used in order to investigate the dependence of the induced lac expression on stimulation by cyclic AMP after the shift to non-permissive temperature. High temperature lowered the rate of beta-galactosidase synthesis. However, the low rate of synthesis could be strongly increased by cyclic AMP (30, 2.4 and 5.7-fold increases for tsX, A2R7 and R120 mutants, respectively). At the permissive temperature stimulation by cyclic AMP was less than 1.4-fold (minimal medium supplemented with glycerol). The results suggest that the maximal expression of the lac operon is saturated, that is, a hypothetical increase in RNA polymerase or cAMP-CRP concentration in the cell with not enhance the expression. The concept of saturation explains why it was possible to increase the beta-galactosidase synthesis in conditions of limited promoter binding activity of RNA polymerase through increase in concentration of cyclic AMP-CRP complex in the cell (addition of cyclic AMP) to the values higher than that observed on glycerol.", "contents": "Expression of the lac operon in RNA polymerase mutants of Escherichia coli K12. Three temperature-sensitive mutant strains for RNA polymerase beta or beta' subunits (carrying mutations tsx, A2R7 and R120) were used in order to investigate the dependence of the induced lac expression on stimulation by cyclic AMP after the shift to non-permissive temperature. High temperature lowered the rate of beta-galactosidase synthesis. However, the low rate of synthesis could be strongly increased by cyclic AMP (30, 2.4 and 5.7-fold increases for tsX, A2R7 and R120 mutants, respectively). At the permissive temperature stimulation by cyclic AMP was less than 1.4-fold (minimal medium supplemented with glycerol). The results suggest that the maximal expression of the lac operon is saturated, that is, a hypothetical increase in RNA polymerase or cAMP-CRP concentration in the cell with not enhance the expression. The concept of saturation explains why it was possible to increase the beta-galactosidase synthesis in conditions of limited promoter binding activity of RNA polymerase through increase in concentration of cyclic AMP-CRP complex in the cell (addition of cyclic AMP) to the values higher than that observed on glycerol."}
{"id": "PMID:225642", "title": "Separation of four components of the phosphoenolpyruvate: glucose phosphotransferase system in Vibrio parahaemolyticus.", "content": "Four classes of Vibrio parahaemolyticus mutants defective in the phosphoenolpyruvate: glucose phosphotransferase system (PTS) are described. They were phenotypically different, and were defective in different PTS components. The components designated tentatively as II, I, III, and H were separated by gel filtration of a wild-type extract. Component II, which was specific for glucose and found in the particulate fraction, is probably membrane-bound, glucose-specific enzyme II. Both components I and H were soluble proteins, and the latter was relatively heat-stable. Component I was required for phosphorylation of glucose, trehalose, fructose, mannose, and mannitol. Component H was also required for phosphorylating all the above sugars except fructose. These and some additional findings strongly suggest that components I and H correspond to enzyme I and HPr, respectively. Component III, a soluble heat-stable protein, may be equivalent to the sugar-specific factor III found in other organisms, although it seems to participate in phosphorylating two sugars, glucose and trehalose. There were evidences that mutants defective in components I and III were deficient in cyclic adenosine 3',5'-monophosphate synthesis under certain conditions.", "contents": "Separation of four components of the phosphoenolpyruvate: glucose phosphotransferase system in Vibrio parahaemolyticus. Four classes of Vibrio parahaemolyticus mutants defective in the phosphoenolpyruvate: glucose phosphotransferase system (PTS) are described. They were phenotypically different, and were defective in different PTS components. The components designated tentatively as II, I, III, and H were separated by gel filtration of a wild-type extract. Component II, which was specific for glucose and found in the particulate fraction, is probably membrane-bound, glucose-specific enzyme II. Both components I and H were soluble proteins, and the latter was relatively heat-stable. Component I was required for phosphorylation of glucose, trehalose, fructose, mannose, and mannitol. Component H was also required for phosphorylating all the above sugars except fructose. These and some additional findings strongly suggest that components I and H correspond to enzyme I and HPr, respectively. Component III, a soluble heat-stable protein, may be equivalent to the sugar-specific factor III found in other organisms, although it seems to participate in phosphorylating two sugars, glucose and trehalose. There were evidences that mutants defective in components I and III were deficient in cyclic adenosine 3',5'-monophosphate synthesis under certain conditions."}
{"id": "PMID:225643", "title": "Effect of certain inhibitors of glycoprotein synthesis on cell fusion induced by vesicular stomatitis virus.", "content": "The effect of certain metabolic inhibitors on the fusion of BHK-21 cells induced by vesicular stomatitis virus (VSV) was studied. The polykaryocyte formation in infected cells and virus growth were inhibited by 2-deoxy-D-glucose and D-glucosamine. Host-cell proteins synthesis was suppressed profoundly in both BHK-21-KB and B cells infected with VSV. On the other hand, glycoprotein synthesis was significantly enhanced during the polykaryocyte formation in BHK-21-KB cells, while it was suppressed in BHK-21-B cells which were not sensitive to cell fusion by VSV.", "contents": "Effect of certain inhibitors of glycoprotein synthesis on cell fusion induced by vesicular stomatitis virus. The effect of certain metabolic inhibitors on the fusion of BHK-21 cells induced by vesicular stomatitis virus (VSV) was studied. The polykaryocyte formation in infected cells and virus growth were inhibited by 2-deoxy-D-glucose and D-glucosamine. Host-cell proteins synthesis was suppressed profoundly in both BHK-21-KB and B cells infected with VSV. On the other hand, glycoprotein synthesis was significantly enhanced during the polykaryocyte formation in BHK-21-KB cells, while it was suppressed in BHK-21-B cells which were not sensitive to cell fusion by VSV."}
{"id": "PMID:225644", "title": "IgM and IgG response to sheep red blood cells in mouse hepatitis virus-infected nude mice.", "content": "In nude mice which originally had no ability to respond to sheep red blood cells, an enhanced response to the same antigen with IgM-IgG switching was demonstrated during subacute infection with mouse hepatitis virus. IgM antibody-producing cells in the spleen were detected at days 2 to 6 after the antigen injection and IgG antibody-producing cells appeared at day 6 or later. The secondary IgG response, though not remarkable, was recognized after reinjection of the antigen 10 days after the first injection.", "contents": "IgM and IgG response to sheep red blood cells in mouse hepatitis virus-infected nude mice. In nude mice which originally had no ability to respond to sheep red blood cells, an enhanced response to the same antigen with IgM-IgG switching was demonstrated during subacute infection with mouse hepatitis virus. IgM antibody-producing cells in the spleen were detected at days 2 to 6 after the antigen injection and IgG antibody-producing cells appeared at day 6 or later. The secondary IgG response, though not remarkable, was recognized after reinjection of the antigen 10 days after the first injection."}
{"id": "PMID:225647", "title": "A study of transfer factor for opportunistic infections in cancer patients.", "content": "Although supportive care during therapy of patients with malignancies has improved, infection remains the major cause of death in these patients. The problem of \"opportunistic\" infections is becoming more apparent as better antibiotics are found. The control of these infections depends in part on mechanisms of cell-mediated immunity. It has been demonstrated that delayed-type hypersensitivity can be transferred from one person to another. Therefore, we used transfer factor in the treatment of 15 patients, most with leukemia, who had fungal, viral, or mycobacterial infections that were not responding to conventional therapy. Seven of ten evaluable patients had therapeutic control of their infections while receiving transfer factor. Transfer factor appears to have contributed to these clinical improvements and is a modality of treatment that deserves further investigation.", "contents": "A study of transfer factor for opportunistic infections in cancer patients. Although supportive care during therapy of patients with malignancies has improved, infection remains the major cause of death in these patients. The problem of \"opportunistic\" infections is becoming more apparent as better antibiotics are found. The control of these infections depends in part on mechanisms of cell-mediated immunity. It has been demonstrated that delayed-type hypersensitivity can be transferred from one person to another. Therefore, we used transfer factor in the treatment of 15 patients, most with leukemia, who had fungal, viral, or mycobacterial infections that were not responding to conventional therapy. Seven of ten evaluable patients had therapeutic control of their infections while receiving transfer factor. Transfer factor appears to have contributed to these clinical improvements and is a modality of treatment that deserves further investigation."}
{"id": "PMID:225648", "title": "Wilms tumor with extension to the right atrium.", "content": "A seven-year-old boy had cardiac symptoms for five months before the diagnosis of Wilms tumor was made. The tumor extended into the inferior vena cava through the renal vein and protruded into the right atrium. All demonstrable tumor masses could be removed at a one-step surgical procedure without using cardiopulmonary bypass. Intensive postoperative chemotherapy has been given, and 15 months after surgery he was without signs of relapse.", "contents": "Wilms tumor with extension to the right atrium. A seven-year-old boy had cardiac symptoms for five months before the diagnosis of Wilms tumor was made. The tumor extended into the inferior vena cava through the renal vein and protruded into the right atrium. All demonstrable tumor masses could be removed at a one-step surgical procedure without using cardiopulmonary bypass. Intensive postoperative chemotherapy has been given, and 15 months after surgery he was without signs of relapse."}
{"id": "PMID:225646", "title": "[Lithotrophic metabolic elements in the obligate methylotroph, Methylococcus thermophilus].", "content": "Methane oxidizing bacteria oxidize ammonium via hydroxylamine to nitrite. Electrons liberated upon oxidation of hydroxylamine are transported, depending on the conditions, by the components of the respiratory chain either to oxygen or to pyridine nucleotide. In the former case, the process is coupled with ATP synthesis which occurs at the level of terminal oxidase; in the latter case, NAD+ is reduced by the energy-dependent reversed electron flow in the respiratory chain. The level of nitrite accumulation in the culture liquid of methane oxidizing bacteria suggests that the process of ammonium nitrification is a necessary step of their metabolism. Therefore, oxidation of the mineral component of the growth medium (i. e. ammonium) is an additional source of metabolic energy for the obligate methane oxidizing bacterium Methylococcus thermophilus. Operation of the lithotrophic type of mechanism for energy production at the account of ammonium oxidation makes methane oxidizing bacteria similar to nitrifying microorganisms.", "contents": "[Lithotrophic metabolic elements in the obligate methylotroph, Methylococcus thermophilus]. Methane oxidizing bacteria oxidize ammonium via hydroxylamine to nitrite. Electrons liberated upon oxidation of hydroxylamine are transported, depending on the conditions, by the components of the respiratory chain either to oxygen or to pyridine nucleotide. In the former case, the process is coupled with ATP synthesis which occurs at the level of terminal oxidase; in the latter case, NAD+ is reduced by the energy-dependent reversed electron flow in the respiratory chain. The level of nitrite accumulation in the culture liquid of methane oxidizing bacteria suggests that the process of ammonium nitrification is a necessary step of their metabolism. Therefore, oxidation of the mineral component of the growth medium (i. e. ammonium) is an additional source of metabolic energy for the obligate methane oxidizing bacterium Methylococcus thermophilus. Operation of the lithotrophic type of mechanism for energy production at the account of ammonium oxidation makes methane oxidizing bacteria similar to nitrifying microorganisms."}
{"id": "PMID:225657", "title": "Regulatory and functional compartment of three multifunctional protein kinase systems.", "content": "Cyclic AMP-dependent protein kinase has been well established to be composed of catalytic and regulatory subunits, and cyclic AMP acts to dissociate these subunits to exhibit full enzymatic activity. In contrast, cyclic GMP-dependent protein kinase does not possess such a subunit structure and is activated by cyclic GMP simply in an allosteric manner. In addition to cyclic AMP-dependent and cyclic GMP-dependent protein kinases, another species of multifunctional protein kinase has been found in many mammalian tissues. This protein kinase is entirely independent of cyclic nucleotides and activated by lower concentrations of Ca2+ in the presence of a membrane-associated factor. This factor has been identified as phospholipids; in fact, phosphatidylinositol and phosphatidylserine are active in this role, whereas lecithin and sphingomyelin are unable to activate the enzyme. Thus, the three species of protein kinases mentioned above are activated in different manners. Nevertheless, these enzymes show very similar substrate specificities and phosphorylate the same specific seryl residues of histone fractions. In addition, all enzymes have abilities to activate and inactivate muscle phosphorylase kinase and glycogen synthetase, respectively, although the relative rates of reactions towards various substrates are markedly different. The Ca2+-dependent protein kinase seems to be associated with membranous components, whereas cyclic GMP-dependent protein kinase appears to be related to certain subcellular organella such as nucleus. Suggestive evidence is available implying that the cyclic AMP-, cyclic GMP- and Ca2+-activated three sets of protein kinase systems may play each specific physiological roles presumably owing to their own subcellular compartments.", "contents": "Regulatory and functional compartment of three multifunctional protein kinase systems. Cyclic AMP-dependent protein kinase has been well established to be composed of catalytic and regulatory subunits, and cyclic AMP acts to dissociate these subunits to exhibit full enzymatic activity. In contrast, cyclic GMP-dependent protein kinase does not possess such a subunit structure and is activated by cyclic GMP simply in an allosteric manner. In addition to cyclic AMP-dependent and cyclic GMP-dependent protein kinases, another species of multifunctional protein kinase has been found in many mammalian tissues. This protein kinase is entirely independent of cyclic nucleotides and activated by lower concentrations of Ca2+ in the presence of a membrane-associated factor. This factor has been identified as phospholipids; in fact, phosphatidylinositol and phosphatidylserine are active in this role, whereas lecithin and sphingomyelin are unable to activate the enzyme. Thus, the three species of protein kinases mentioned above are activated in different manners. Nevertheless, these enzymes show very similar substrate specificities and phosphorylate the same specific seryl residues of histone fractions. In addition, all enzymes have abilities to activate and inactivate muscle phosphorylase kinase and glycogen synthetase, respectively, although the relative rates of reactions towards various substrates are markedly different. The Ca2+-dependent protein kinase seems to be associated with membranous components, whereas cyclic GMP-dependent protein kinase appears to be related to certain subcellular organella such as nucleus. Suggestive evidence is available implying that the cyclic AMP-, cyclic GMP- and Ca2+-activated three sets of protein kinase systems may play each specific physiological roles presumably owing to their own subcellular compartments."}
{"id": "PMID:225661", "title": "Metchnikoff-Schaumann bodies in experimental Yersin's type tuberculosis induced with Mycobacterium avium in hamster.", "content": "Structure and ultrastructure of Metchnikoff-Schaumann bodies occurring in macrophages, epithelioid cells and multinucleated giant cells in tuberculous granuloma were investigated. Their similitude with other reported intracellular calcareous bodies occurring in malakoplakia, infectious orchitis (Michaelis-Guttman' bodies or calcosphaerites), in beryllium granulomas (conchoid bodies) and sarcoidosis (Schaumann bodies) is discussed.", "contents": "Metchnikoff-Schaumann bodies in experimental Yersin's type tuberculosis induced with Mycobacterium avium in hamster. Structure and ultrastructure of Metchnikoff-Schaumann bodies occurring in macrophages, epithelioid cells and multinucleated giant cells in tuberculous granuloma were investigated. Their similitude with other reported intracellular calcareous bodies occurring in malakoplakia, infectious orchitis (Michaelis-Guttman' bodies or calcosphaerites), in beryllium granulomas (conchoid bodies) and sarcoidosis (Schaumann bodies) is discussed."}
{"id": "PMID:225660", "title": "Bronchiolo-alveolar cell carcinomas. A histopathologic analysis of 125 cases.", "content": "A hundred and twenty-five cases of bronchiolo-alveolar cell carcinomas observed between 1954 and 1978 were histopathologically analysed, some of them also histoenzymatically. The material comprised 93 lung resections (56 lobectomies and 37 pulmonectomies). 11 intraoperatory biopsies in inoperable cases, and 21 autopsies. The early discovery and treatment of the overwhelming majority of cases allow the observation of uncomplicated lesions, the bronchiolar involvement followed by alveolar invasion due to sliding of neoplastic cells on denuded alveolar walls often thickened by cell and fibril accumulation, the papillary formations, as well as the histoenzymatic behaviour. The latter evidenced the strong relations of neoplastic cells with the normal bronchiolar cells (glucose-6-phosphate dehydrogenase. Mg-dependent ATP-ase, oxidoreductases). Some peculiarities also point to the existence of a possible second parallel origin of neoplastic cells at the level of large alveolocytes during the morphogenesis of this multicentric lung carcinoma.", "contents": "Bronchiolo-alveolar cell carcinomas. A histopathologic analysis of 125 cases. A hundred and twenty-five cases of bronchiolo-alveolar cell carcinomas observed between 1954 and 1978 were histopathologically analysed, some of them also histoenzymatically. The material comprised 93 lung resections (56 lobectomies and 37 pulmonectomies). 11 intraoperatory biopsies in inoperable cases, and 21 autopsies. The early discovery and treatment of the overwhelming majority of cases allow the observation of uncomplicated lesions, the bronchiolar involvement followed by alveolar invasion due to sliding of neoplastic cells on denuded alveolar walls often thickened by cell and fibril accumulation, the papillary formations, as well as the histoenzymatic behaviour. The latter evidenced the strong relations of neoplastic cells with the normal bronchiolar cells (glucose-6-phosphate dehydrogenase. Mg-dependent ATP-ase, oxidoreductases). Some peculiarities also point to the existence of a possible second parallel origin of neoplastic cells at the level of large alveolocytes during the morphogenesis of this multicentric lung carcinoma."}
{"id": "PMID:225666", "title": "Collagenase in the lower respiratory tract of patients with idiopathic pulmonary fibrosis.", "content": "To test the hypothesis that idiopathic pulmonary fibrosis (IPF) is mediated through collagenase present in the lower respiratory tract, we used the fiberoptic bronchoscope to obtain fluid from the lower respiratory tract of 24 patients with IPF, 18 controls and nine patients with sarcoidosis. The fluid was analyzed for a variety of enzymes, including collagenase. Fifteen of 21 patients with IPF showed collagenase activity, whereas normal controls and patients with sarcoidosis showed none (P greater than 0.001, for all comparisons). In two patients with IPF who were re-evaluated after eight to 24 months, the collagenase activity was persistent. Fluid from patients with IPF also contained elevated levels of a non-specific neutral protease (P greater than 0.01 compared with controls), but there was no elastase activity in fluid from patients with IPF or from controls. The collagenase found in lavage fluid in IPF cleaved lung collagen into collagenase-specific TCA and TCB fragments. We conclude that in IPF the collagen of the lung is subjected to sustained lysis, followed by disordered resynthesis, and that the presence of active collagenase in the lower respiratory tract is a specific feature of the alveolitis associated with this disease.", "contents": "Collagenase in the lower respiratory tract of patients with idiopathic pulmonary fibrosis. To test the hypothesis that idiopathic pulmonary fibrosis (IPF) is mediated through collagenase present in the lower respiratory tract, we used the fiberoptic bronchoscope to obtain fluid from the lower respiratory tract of 24 patients with IPF, 18 controls and nine patients with sarcoidosis. The fluid was analyzed for a variety of enzymes, including collagenase. Fifteen of 21 patients with IPF showed collagenase activity, whereas normal controls and patients with sarcoidosis showed none (P greater than 0.001, for all comparisons). In two patients with IPF who were re-evaluated after eight to 24 months, the collagenase activity was persistent. Fluid from patients with IPF also contained elevated levels of a non-specific neutral protease (P greater than 0.01 compared with controls), but there was no elastase activity in fluid from patients with IPF or from controls. The collagenase found in lavage fluid in IPF cleaved lung collagen into collagenase-specific TCA and TCB fragments. We conclude that in IPF the collagen of the lung is subjected to sustained lysis, followed by disordered resynthesis, and that the presence of active collagenase in the lower respiratory tract is a specific feature of the alveolitis associated with this disease."}
{"id": "PMID:225667", "title": "Tissue differentiation and susceptibility to embryonal tumor induction by ethylnitrosourea in the opossum.", "content": "Opossums (Didelphis virginiana Kerr) exposed to 100 mg ENU/kg in single or incremental doses early in postnatal life developed a spectrum of epithelial and mesenchymal neoplasms including several types of embryonal neoplasms not previously induced in laboratory animals. A correlation was apparent to a varying degree between susceptibility to tumor induction and the state of morphologic maturation of the presumed target tissues at the light microscopic level for embryonal tumors of the eye, kidney, and brain. The susceptibility of the opossum eye to an ENU-induced intraocular teratoid medulloepithelioma extended over the period from 1 to between 3 and 4 weeks of age and was correlated with the differentiation of the apparent target cell, the nonpigmented ciliary epithelium of the pars ciliaris retinae. Induction of nephroblastomas was correlated with the presence in the kidney of stem cells (metanephric blastema) through the period from birth to between 6 and 8 weeks of age. Although susceptibility of the opossum brain to ENU induction of gangliogliomas was correlated with the state of differentiation of the germinal matrix from birth to 56 days of age, induction of these tumors was essentially limited to the 1st week postpartum. No definite correlation between vulnerability to tumor induction and tissue maturation was evident for a tumor of the jaw (ameloblastoma) with presumed origin from embryonic dental remnants. Our results indicated that the opossium early in postnatal life is a useful model for the induction and characterization of certain of the major dysontogenetic tumors, which have been difficult or impossible to reproduce in the traditional laboratory species.", "contents": "Tissue differentiation and susceptibility to embryonal tumor induction by ethylnitrosourea in the opossum. Opossums (Didelphis virginiana Kerr) exposed to 100 mg ENU/kg in single or incremental doses early in postnatal life developed a spectrum of epithelial and mesenchymal neoplasms including several types of embryonal neoplasms not previously induced in laboratory animals. A correlation was apparent to a varying degree between susceptibility to tumor induction and the state of morphologic maturation of the presumed target tissues at the light microscopic level for embryonal tumors of the eye, kidney, and brain. The susceptibility of the opossum eye to an ENU-induced intraocular teratoid medulloepithelioma extended over the period from 1 to between 3 and 4 weeks of age and was correlated with the differentiation of the apparent target cell, the nonpigmented ciliary epithelium of the pars ciliaris retinae. Induction of nephroblastomas was correlated with the presence in the kidney of stem cells (metanephric blastema) through the period from birth to between 6 and 8 weeks of age. Although susceptibility of the opossum brain to ENU induction of gangliogliomas was correlated with the state of differentiation of the germinal matrix from birth to 56 days of age, induction of these tumors was essentially limited to the 1st week postpartum. No definite correlation between vulnerability to tumor induction and tissue maturation was evident for a tumor of the jaw (ameloblastoma) with presumed origin from embryonic dental remnants. Our results indicated that the opossium early in postnatal life is a useful model for the induction and characterization of certain of the major dysontogenetic tumors, which have been difficult or impossible to reproduce in the traditional laboratory species."}
{"id": "PMID:225668", "title": "Mutagenesis and embryonal carcinogenesis.", "content": "The embryonal tumors of children occur in dominantly heritable and nonhereditary forms, which indicates that a dominant mutation can be on the carcinogenic pathway. A model which fits age-specific incidence hypothesizes that both forms arise as a consequence of two mutations. The background incidences of these tumors then reflect spontaneous mutation rates in germinal and somatic cells and may be increased by mutagens. The gene for one tumor (retinoblastoma) seems to be located on chromosome 13. Clues to the pathophysiology of these tumor genes come from consideration of their tissue specificity, origin from embryonal cells, and developmental effects. Childhood cancers may be manifestations of the homozygous states of a series of genes concerned with differentiation in specific embryonal tissues.", "contents": "Mutagenesis and embryonal carcinogenesis. The embryonal tumors of children occur in dominantly heritable and nonhereditary forms, which indicates that a dominant mutation can be on the carcinogenic pathway. A model which fits age-specific incidence hypothesizes that both forms arise as a consequence of two mutations. The background incidences of these tumors then reflect spontaneous mutation rates in germinal and somatic cells and may be increased by mutagens. The gene for one tumor (retinoblastoma) seems to be located on chromosome 13. Clues to the pathophysiology of these tumor genes come from consideration of their tissue specificity, origin from embryonal cells, and developmental effects. Childhood cancers may be manifestations of the homozygous states of a series of genes concerned with differentiation in specific embryonal tissues."}
{"id": "PMID:225669", "title": "Perinatal induction of medulloblastomas in Syrian golden hamsters by a human polyoma virus (JC).", "content": "Medulloblastomas, originating from cells of the internal granular layer of the cerebellum, developed in Syrian golden hamsters 3--6 months after inoculation at birth intracerebrally and sc with JC virus, a papovavirus isolated originally from a human case of the demyelinating disease progressive multifocal leukoencephalopathy. The lesion is compared with the human medulloblastoma of childhood. JC virus is the first infectious agent to produce such a neoplasm in any species.", "contents": "Perinatal induction of medulloblastomas in Syrian golden hamsters by a human polyoma virus (JC). Medulloblastomas, originating from cells of the internal granular layer of the cerebellum, developed in Syrian golden hamsters 3--6 months after inoculation at birth intracerebrally and sc with JC virus, a papovavirus isolated originally from a human case of the demyelinating disease progressive multifocal leukoencephalopathy. The lesion is compared with the human medulloblastoma of childhood. JC virus is the first infectious agent to produce such a neoplasm in any species."}
{"id": "PMID:225670", "title": "Problems and perspectives in perinatal carcinogenesis: a summary of the conference.", "content": "The proceedings of the Conference are summarized in the context of current understanding of perinatal susceptibility to carcinogenic agents. The consequences of exposure to either metabolism-dependent or direct-acting chemical carcinogens during fetal or neonatal life are quantitatively different from the effects of comparable doses of the same agents in adults. The nature of these differences and their relevance both for preventive medicine and for application to bioassay procedures for detection of suspected carcinogens are discussed for conventional (chemically reactive) carcinogenic compounds and for hormones. The degree of tissue differentiation at the time of exposure to a carcinogen and the genetics of the subject have been shown to affect susceptibility to induction of embryonal and differentiated types of tumors and by both chemical agents (including hormones) and viruses. The desirability of conducting parallel studies in two or more species when investigating mechanisms of perinatal/adult differences in susceptibility to carcinogens is emphasized.", "contents": "Problems and perspectives in perinatal carcinogenesis: a summary of the conference. The proceedings of the Conference are summarized in the context of current understanding of perinatal susceptibility to carcinogenic agents. The consequences of exposure to either metabolism-dependent or direct-acting chemical carcinogens during fetal or neonatal life are quantitatively different from the effects of comparable doses of the same agents in adults. The nature of these differences and their relevance both for preventive medicine and for application to bioassay procedures for detection of suspected carcinogens are discussed for conventional (chemically reactive) carcinogenic compounds and for hormones. The degree of tissue differentiation at the time of exposure to a carcinogen and the genetics of the subject have been shown to affect susceptibility to induction of embryonal and differentiated types of tumors and by both chemical agents (including hormones) and viruses. The desirability of conducting parallel studies in two or more species when investigating mechanisms of perinatal/adult differences in susceptibility to carcinogens is emphasized."}
{"id": "PMID:225671", "title": "Single strands induce recA protein to unwind duplex DNA for homologous pairing.", "content": "Single-stranded DNA, whether homologous or not, stimulates purified Escherichia coli recA protein to unwind duplex DNA. This helps to explain how recA promotes a search for homology in genetic recombination. As oligodeoxynucleotide also stimulate unwinding, a common mechanism may relate the function of recA protein in recombination to other functions (SOS) induced by oligonucleotides.", "contents": "Single strands induce recA protein to unwind duplex DNA for homologous pairing. Single-stranded DNA, whether homologous or not, stimulates purified Escherichia coli recA protein to unwind duplex DNA. This helps to explain how recA promotes a search for homology in genetic recombination. As oligodeoxynucleotide also stimulate unwinding, a common mechanism may relate the function of recA protein in recombination to other functions (SOS) induced by oligonucleotides."}
{"id": "PMID:225672", "title": "The src gene product of transformed and morphologically reverted ASV-infected mammalian cells.", "content": "Morphological revertants of avian sarcoma virus transformed vole cells contain the sarcoma gene product (pp60src) in an enzymatically active form, suggesting that the presence of pp60src protein kinase activity is infussicient to induce morphological transformation. Structural analyses of pp60src from infected vole cell clones suggest that in one of the revertant clones on alteration in pp60src may be responsible for morphological reversion while in a second clone, reversion may result from an alteration in a cell gene product with which pp60src must interact. As these morphological revertant cells are tumorigenic, different cell components are required to interact with pp60src to facilitate the two events.", "contents": "The src gene product of transformed and morphologically reverted ASV-infected mammalian cells. Morphological revertants of avian sarcoma virus transformed vole cells contain the sarcoma gene product (pp60src) in an enzymatically active form, suggesting that the presence of pp60src protein kinase activity is infussicient to induce morphological transformation. Structural analyses of pp60src from infected vole cell clones suggest that in one of the revertant clones on alteration in pp60src may be responsible for morphological reversion while in a second clone, reversion may result from an alteration in a cell gene product with which pp60src must interact. As these morphological revertant cells are tumorigenic, different cell components are required to interact with pp60src to facilitate the two events."}
{"id": "PMID:225674", "title": "Vanadate inhibits uncoupled Ca efflux but not Na--Ca exchange in squid axons.", "content": "Nerve cells can maintain a very low intracellular calcium concentration ([Ca2+]i) against large Ca2+ electrochemical gradients (see ref. 1 for review). The properties of the calcium efflux from these cells depend on [Ca2+]i (ref. 2), and within the physiological range, most Ca efflux depends on ATP (which stimulates with high affinity) and is insensitive to Na1, Na0 and Ca0 (uncoupled Ca efflux). When the [Ca2+]i is well above the physiological range, Ca efflux becomes only partially dependent on ATP (acting now with low affinity), is inhibited by Nai and is stimulated by Na0 and Ca0 (Na--Ca exchange). Orthovanadate, a powerful inhibitor of the (Na+ + K+)ATPase and the Na pump, also inhibits the Ca-stimulated ATPase activity, which is the enzymatic basis for the uncoupled Ca pump, in human red cells. The experiments reported here show that in squid axons the ATP-dependent uncoupled Ca efflux can be fully and reversibly inhibited by vanadate, whereas concentrations of vanadate 10 times higher have no effect on the Na--Ca exchange. This is another indication that the uncoupled Ca efflux represents an ATP-driven Ca pump, and supports the suggestion that the uncoupled Ca efflux and Na--Ca exchange are mediated by different mechanisms.", "contents": "Vanadate inhibits uncoupled Ca efflux but not Na--Ca exchange in squid axons. Nerve cells can maintain a very low intracellular calcium concentration ([Ca2+]i) against large Ca2+ electrochemical gradients (see ref. 1 for review). The properties of the calcium efflux from these cells depend on [Ca2+]i (ref. 2), and within the physiological range, most Ca efflux depends on ATP (which stimulates with high affinity) and is insensitive to Na1, Na0 and Ca0 (uncoupled Ca efflux). When the [Ca2+]i is well above the physiological range, Ca efflux becomes only partially dependent on ATP (acting now with low affinity), is inhibited by Nai and is stimulated by Na0 and Ca0 (Na--Ca exchange). Orthovanadate, a powerful inhibitor of the (Na+ + K+)ATPase and the Na pump, also inhibits the Ca-stimulated ATPase activity, which is the enzymatic basis for the uncoupled Ca pump, in human red cells. The experiments reported here show that in squid axons the ATP-dependent uncoupled Ca efflux can be fully and reversibly inhibited by vanadate, whereas concentrations of vanadate 10 times higher have no effect on the Na--Ca exchange. This is another indication that the uncoupled Ca efflux represents an ATP-driven Ca pump, and supports the suggestion that the uncoupled Ca efflux and Na--Ca exchange are mediated by different mechanisms."}
{"id": "PMID:225677", "title": "Curare has a voltage-dependent blocking action on the glutamate synapse.", "content": "The skeletal muscle of members of Orthoptera and Diptera receives an innervation which is probably glutaminergic. Recent study of the ventral muscle fibres in the larvae of the beetle, Tenebrio molitor, has revealed that the transmitter action can be mimicked by the iontophoretic application of L-glutamate to the junctional sites at which the extracellular excitatory postsynaptic potentials (e.p.s.ps) could be recorded (D.Y. and H.W., unpublished observation). Contrary to the evidence favouring glutamate as a transmitter of junctional excitation in insects, some investigators have found that curare (+)tubocrarine, TC), a classic acetylcholine (ACh) antagonist, suppresses the neurally evoked muscle potentials in the fly Sacophaga, and Tenebrio. Here, we have analysed the action of curare on the neuromuscular junction of Tenebrio larvae and found that curare blocked the glutaminergic transmission by antagonising the transmitter at the postsynaptic site.", "contents": "Curare has a voltage-dependent blocking action on the glutamate synapse. The skeletal muscle of members of Orthoptera and Diptera receives an innervation which is probably glutaminergic. Recent study of the ventral muscle fibres in the larvae of the beetle, Tenebrio molitor, has revealed that the transmitter action can be mimicked by the iontophoretic application of L-glutamate to the junctional sites at which the extracellular excitatory postsynaptic potentials (e.p.s.ps) could be recorded (D.Y. and H.W., unpublished observation). Contrary to the evidence favouring glutamate as a transmitter of junctional excitation in insects, some investigators have found that curare (+)tubocrarine, TC), a classic acetylcholine (ACh) antagonist, suppresses the neurally evoked muscle potentials in the fly Sacophaga, and Tenebrio. Here, we have analysed the action of curare on the neuromuscular junction of Tenebrio larvae and found that curare blocked the glutaminergic transmission by antagonising the transmitter at the postsynaptic site."}
{"id": "PMID:225678", "title": "Orthotopic bone induction at sites of Moloney murine sarcoma virus inoculation in mice.", "content": "Moloney murine sarcoma virus (M-MSV) induces at the site of inoculation in newborn and adult mice and rats various types of sarcoma, including osteosarcoma. The induced tumours are fatal in newborn, whereas sarcomas developed in adult animals regress spontaneously. The regression is mediated mainly by a cellular response. We have now demonstrated that the presence of sarcomas induced by M-MSV is a powerful stimulus for periosteal osteogenesis around tumour masses. Orthotopically induced osteogenesis by M-MSV may serve as a model for local regulation of bone growth and for cell differentiation studies, and may help explain the aetiology of some human bone disorders.", "contents": "Orthotopic bone induction at sites of Moloney murine sarcoma virus inoculation in mice. Moloney murine sarcoma virus (M-MSV) induces at the site of inoculation in newborn and adult mice and rats various types of sarcoma, including osteosarcoma. The induced tumours are fatal in newborn, whereas sarcomas developed in adult animals regress spontaneously. The regression is mediated mainly by a cellular response. We have now demonstrated that the presence of sarcomas induced by M-MSV is a powerful stimulus for periosteal osteogenesis around tumour masses. Orthotopically induced osteogenesis by M-MSV may serve as a model for local regulation of bone growth and for cell differentiation studies, and may help explain the aetiology of some human bone disorders."}
{"id": "PMID:225679", "title": "Superoxide involvement in the bactericidal effects of negative air ions on Staphylococcus albus.", "content": "The physical nature of small air ions is well established and it is recognized that they can produce a variety of biological effects. However, in only a few instances have any underlying biochemical changes been detected. Theoretically, one can consider the hydrated superoxide radical anion (O2) (H2O)n with n congruent to 4-8 as a likely candidate for a biologically active species of negative air ion. The chemical and biological reactivity of superoxide is high and includes a leading role in bacterial killing caused by radiation, in which superoxide dismutase (SOD), an enzyme that catalyses the reaction: O2 + O2 +2H leads to H2O2 +O2 protected markedly. Other studies have also demonstrated the bactericidal effect of O2 (refs 9-11). Inasmuch as the bactericidal action of small negative air ions has been repeatedly confirmed, we decided to test for the involvement of O2 in this phenomenon by evaluating the protective effect of SOD. Our results show strong O2 involvement in negative air ion bacterial kill.", "contents": "Superoxide involvement in the bactericidal effects of negative air ions on Staphylococcus albus. The physical nature of small air ions is well established and it is recognized that they can produce a variety of biological effects. However, in only a few instances have any underlying biochemical changes been detected. Theoretically, one can consider the hydrated superoxide radical anion (O2) (H2O)n with n congruent to 4-8 as a likely candidate for a biologically active species of negative air ion. The chemical and biological reactivity of superoxide is high and includes a leading role in bacterial killing caused by radiation, in which superoxide dismutase (SOD), an enzyme that catalyses the reaction: O2 + O2 +2H leads to H2O2 +O2 protected markedly. Other studies have also demonstrated the bactericidal effect of O2 (refs 9-11). Inasmuch as the bactericidal action of small negative air ions has been repeatedly confirmed, we decided to test for the involvement of O2 in this phenomenon by evaluating the protective effect of SOD. Our results show strong O2 involvement in negative air ion bacterial kill."}
{"id": "PMID:225691", "title": "Rate of disappearance of isethionic acid in the rat central nervous system.", "content": "The rates of disappearance of tritiated isethionic acid (2-hydroxyethanesulfonic acid) in eight regions of the rat central nervous system were studied. By utilizing the technique of graphical analysis (\"curve peeling\"), it was determined that seven areas (striatum, diencephalon, pons-medulla, midbrain, hippocampus, spinal cord, and cortex) exhibited triphasic (fast, intermediate, and slow) disappearance rates while only the cerebellum displayed a biphasic (fast, slow) rate. The half-lives for the fast component in the different regions of the central nervous system varied from 0.5 hr (midbrain and cortex) to 1.5 hr (diencephalon, cerebellum, and spinal cord): the half-lives for the intermediate component of the triphasic rate varied from 3.5 hr in the midbrain and spinal cord to 5.5 hr in the hippocampus. Half-lives estimated for the slow component of the multiphasic rate of disappearance of tritiated isethionic acid ([3H]ISA) varied from 28 hr (cerebellum) to 90 hr (spinal cord).", "contents": "Rate of disappearance of isethionic acid in the rat central nervous system. The rates of disappearance of tritiated isethionic acid (2-hydroxyethanesulfonic acid) in eight regions of the rat central nervous system were studied. By utilizing the technique of graphical analysis (\"curve peeling\"), it was determined that seven areas (striatum, diencephalon, pons-medulla, midbrain, hippocampus, spinal cord, and cortex) exhibited triphasic (fast, intermediate, and slow) disappearance rates while only the cerebellum displayed a biphasic (fast, slow) rate. The half-lives for the fast component in the different regions of the central nervous system varied from 0.5 hr (midbrain and cortex) to 1.5 hr (diencephalon, cerebellum, and spinal cord): the half-lives for the intermediate component of the triphasic rate varied from 3.5 hr in the midbrain and spinal cord to 5.5 hr in the hippocampus. Half-lives estimated for the slow component of the multiphasic rate of disappearance of tritiated isethionic acid ([3H]ISA) varied from 28 hr (cerebellum) to 90 hr (spinal cord)."}
{"id": "PMID:225692", "title": "Anomeric preferences of D-glucose uptake and utilization by cerebral cortex slices of rats.", "content": "On aerobic incubation of rat cerebral cortex slices with anomers of D-glucose and with 2-deoxy-D-glucose (2DG) for 5 min, the disappearance of beta-D-glucose from the incubation mixture was greater than that of alpha-D-glucose and both anomers had a greater rate of disappearance than that of 2DG. In addition, there were significantly greater consumption of oxygen and production of lactate with the beta-anomer than with the alpha-anomer. In similar experiments with 3H-labeled D-glucose anomers and [1-3H]-3-O-methyl-D-glucose (3MG), the accumulation of [1-3H]-beta-D-glucose (up to 5 min) by rat cerebral cortex slices was greater than that of [1-3H]-alpha-D-glucose. Although initially lower than that of the anomers, the accumulation of [1-3H]-3MG increased at a greater rate and, by 5 min of incubation, was greater than that of both glucose anomers. This preferential accumulation was seen to disappear when the slices were preincubated with 2DG (hexokinase inhibitor) or when the temperature of incubation was reduced to 20 degrees C. Under those conditions the data with the glucose anomers were similar to those obtained with 3MG. Our data then suggested that the greater accumulation of beta-D-glucose than of alpha-D-glucose by the slices was probably not due to differences in transport through brain cell membranes but rather to the preferential metabolism of the beta-D-glucose.", "contents": "Anomeric preferences of D-glucose uptake and utilization by cerebral cortex slices of rats. On aerobic incubation of rat cerebral cortex slices with anomers of D-glucose and with 2-deoxy-D-glucose (2DG) for 5 min, the disappearance of beta-D-glucose from the incubation mixture was greater than that of alpha-D-glucose and both anomers had a greater rate of disappearance than that of 2DG. In addition, there were significantly greater consumption of oxygen and production of lactate with the beta-anomer than with the alpha-anomer. In similar experiments with 3H-labeled D-glucose anomers and [1-3H]-3-O-methyl-D-glucose (3MG), the accumulation of [1-3H]-beta-D-glucose (up to 5 min) by rat cerebral cortex slices was greater than that of [1-3H]-alpha-D-glucose. Although initially lower than that of the anomers, the accumulation of [1-3H]-3MG increased at a greater rate and, by 5 min of incubation, was greater than that of both glucose anomers. This preferential accumulation was seen to disappear when the slices were preincubated with 2DG (hexokinase inhibitor) or when the temperature of incubation was reduced to 20 degrees C. Under those conditions the data with the glucose anomers were similar to those obtained with 3MG. Our data then suggested that the greater accumulation of beta-D-glucose than of alpha-D-glucose by the slices was probably not due to differences in transport through brain cell membranes but rather to the preferential metabolism of the beta-D-glucose."}
{"id": "PMID:225693", "title": "Tellurium-induced neuropathy: correlative physiological, morphological and electron microprobe studies.", "content": "Elemental tellurium (TE) was included in the normal diet of 15-day-old rats and every day thereafter for 35 days. Within 24 hours a segmental demyelination was seen in the sciatic nerve. On the 2nd day, Te was localized in the cytoplasm of the Schwann cells. On the 3rd day paralysis of the hind legs appeared which lasted 7--10 days. The papralysis then disappeared and demyelination ceased, although the rats were still ingesting Te. After one week there was also slight demyelination in the brachial plexus. Motor nerve conduction velocities were reduced below the normal control range, but only after the rats had taken Te for a least 7 days. This peripheral neuropathy can only be induced in the rat by Te ingestion between the 15th and 35th days of post-natal life, not before or after this period of time.", "contents": "Tellurium-induced neuropathy: correlative physiological, morphological and electron microprobe studies. Elemental tellurium (TE) was included in the normal diet of 15-day-old rats and every day thereafter for 35 days. Within 24 hours a segmental demyelination was seen in the sciatic nerve. On the 2nd day, Te was localized in the cytoplasm of the Schwann cells. On the 3rd day paralysis of the hind legs appeared which lasted 7--10 days. The papralysis then disappeared and demyelination ceased, although the rats were still ingesting Te. After one week there was also slight demyelination in the brachial plexus. Motor nerve conduction velocities were reduced below the normal control range, but only after the rats had taken Te for a least 7 days. This peripheral neuropathy can only be induced in the rat by Te ingestion between the 15th and 35th days of post-natal life, not before or after this period of time."}
{"id": "PMID:225694", "title": "Widespread intranuclear neuronal corpuscles (Marinesco bodies) associated with a familial spinal degeneration with cranial and peripheral nerve involvement.", "content": "Widespread intranuclear, paranucleolar, acidophilic corpuscles, known as Marinesco bodies, were found in association with degeneration of the posterior columns of ting at the age of 45 years. Neurological examination of his sister (aged 51 years) inciates that she is suffering from the same diseases. The cases appear to belong to the predominantly spinal form of spino-cerebellar degenerations or Friedreich's ataxia. This report, which includes an electron microscope examination, considers the pathological significance of Marinesco bodies.", "contents": "Widespread intranuclear neuronal corpuscles (Marinesco bodies) associated with a familial spinal degeneration with cranial and peripheral nerve involvement. Widespread intranuclear, paranucleolar, acidophilic corpuscles, known as Marinesco bodies, were found in association with degeneration of the posterior columns of ting at the age of 45 years. Neurological examination of his sister (aged 51 years) inciates that she is suffering from the same diseases. The cases appear to belong to the predominantly spinal form of spino-cerebellar degenerations or Friedreich's ataxia. This report, which includes an electron microscope examination, considers the pathological significance of Marinesco bodies."}
{"id": "PMID:225695", "title": "Lymphoblastic transformation in response to viral antigens in multiple sclerosis.", "content": "The blastogenic response of lymphocytes to pokeweed mitogen and a battery of viral antigens was studied in healthy individuals, patients with multiple sclerosis (MS), and patients with other neurologic disorders. The multiple sclerosis patients exhibited a diminished response to pokeweed mitogen and to mumps, parainfluenza, and poliomyelitis I antigens when compared with healthy individuals. However, there was no significant difference between the multiple sclerosis patients and the neurologic control group, except that the MS patients had a better response to measles antigen. The three groups did not differ with regard to herpes antigen. Blocking factors were found in the autologous plasma of all three groups with approximately equal frequency, but were not responsible for the decreased responses noted. A significant inverse correlation was found between disease severity and the blastogenic response to pokeweed mitogen and herpes, parainfluenza, and measles antigens. These findings indicate that the decreased cell-mediated immune response in some MS patients is not specific for any of the viruses tested, and is probably a nonspecific effect of chronic disease. Patients with the relapsing-remitting form of the disease had a higher response to measles antigen and a lower response to pokeweed mitogen than patients with the chronic progressive form of the disease, suggesting that these variants differ immunologically as well as clinically.", "contents": "Lymphoblastic transformation in response to viral antigens in multiple sclerosis. The blastogenic response of lymphocytes to pokeweed mitogen and a battery of viral antigens was studied in healthy individuals, patients with multiple sclerosis (MS), and patients with other neurologic disorders. The multiple sclerosis patients exhibited a diminished response to pokeweed mitogen and to mumps, parainfluenza, and poliomyelitis I antigens when compared with healthy individuals. However, there was no significant difference between the multiple sclerosis patients and the neurologic control group, except that the MS patients had a better response to measles antigen. The three groups did not differ with regard to herpes antigen. Blocking factors were found in the autologous plasma of all three groups with approximately equal frequency, but were not responsible for the decreased responses noted. A significant inverse correlation was found between disease severity and the blastogenic response to pokeweed mitogen and herpes, parainfluenza, and measles antigens. These findings indicate that the decreased cell-mediated immune response in some MS patients is not specific for any of the viruses tested, and is probably a nonspecific effect of chronic disease. Patients with the relapsing-remitting form of the disease had a higher response to measles antigen and a lower response to pokeweed mitogen than patients with the chronic progressive form of the disease, suggesting that these variants differ immunologically as well as clinically."}
{"id": "PMID:225696", "title": "Sterilization of cerebral metastases by radiation therapy.", "content": "It is generally acknowledged that radiation therapy (RT) provides effective palliative treatment for the majority of patients with brain metastases. It is less well known that RT can be \"curative.\" In 10 years, we examined five patients with brain metastases treated with whole-brain radiotherapy and with no residual tumor in the brain at autopsy. These five patients represented about 3 percent (5 of 187) of patients treated for brain metastases and later examined at autopsy. Some metastatic brain tumors are eradicated by RT, and all nonterminal patients should be offered such treatment.", "contents": "Sterilization of cerebral metastases by radiation therapy. It is generally acknowledged that radiation therapy (RT) provides effective palliative treatment for the majority of patients with brain metastases. It is less well known that RT can be \"curative.\" In 10 years, we examined five patients with brain metastases treated with whole-brain radiotherapy and with no residual tumor in the brain at autopsy. These five patients represented about 3 percent (5 of 187) of patients treated for brain metastases and later examined at autopsy. Some metastatic brain tumors are eradicated by RT, and all nonterminal patients should be offered such treatment."}
{"id": "PMID:225697", "title": "Conduction velocities in single fibers of diseased human muscle.", "content": "Focal sarcolemmal lesions, segmental degeneration, and fiber splitting are observed in Duchenne muscular dystrophy and have been proposed to be major contributory causes of dysfunction of this disease. The presence of these abnormalities should affect impulse conduction along the sarcolemma. To test this prediction, we measured conduction velocities of the action potential in normal and diseased human intercostal muscle fibers by means of intracellular microelectrodes. The resting potentials of fibers from patients with Duchenne dystrophy, Becker dystrophy, and motor neuron disease were partially depolarized, and conduction velocities in these fibers were slower than normal. When the membrane potential was artifically hyperpolarized, the conduction velocity in Becker dystrophy fibers was not significantly different from normal. However, conduction velocity values in Duchenne dystrophy or motor neuron disease fibers were significantly lower than normal regardless of the level of membrane hyperpolarization. These data are analyzed in light of the presence of morphologic lesions in the diseased muscle fibers.", "contents": "Conduction velocities in single fibers of diseased human muscle. Focal sarcolemmal lesions, segmental degeneration, and fiber splitting are observed in Duchenne muscular dystrophy and have been proposed to be major contributory causes of dysfunction of this disease. The presence of these abnormalities should affect impulse conduction along the sarcolemma. To test this prediction, we measured conduction velocities of the action potential in normal and diseased human intercostal muscle fibers by means of intracellular microelectrodes. The resting potentials of fibers from patients with Duchenne dystrophy, Becker dystrophy, and motor neuron disease were partially depolarized, and conduction velocities in these fibers were slower than normal. When the membrane potential was artifically hyperpolarized, the conduction velocity in Becker dystrophy fibers was not significantly different from normal. However, conduction velocity values in Duchenne dystrophy or motor neuron disease fibers were significantly lower than normal regardless of the level of membrane hyperpolarization. These data are analyzed in light of the presence of morphologic lesions in the diseased muscle fibers."}
{"id": "PMID:225698", "title": "[Endothyroid (non-chromaffin) branchiomeric paraganglioma. Description of a clinical case].", "content": "A case of endothyroid paraganglioma in a 9-yr-old girl is described. Subtotal lobectomy was performed and the tumour was not recognised until a histological examination has been carried out on a section embedded in paraffin. Only two other cases could be found in the literature. An account is given of the diagnosis of this form, and reference is made to its prognostic aspects since there is a remote possibility that metastasis may occur many years after surgery.", "contents": "[Endothyroid (non-chromaffin) branchiomeric paraganglioma. Description of a clinical case]. A case of endothyroid paraganglioma in a 9-yr-old girl is described. Subtotal lobectomy was performed and the tumour was not recognised until a histological examination has been carried out on a section embedded in paraffin. Only two other cases could be found in the literature. An account is given of the diagnosis of this form, and reference is made to its prognostic aspects since there is a remote possibility that metastasis may occur many years after surgery."}
{"id": "PMID:225700", "title": "[The role of aviation in the epidemiology of smallpox].", "content": "The structure and features of the smallpox virus are described and an account is given of the clinical picture of the disease. Tables and graphs are cited to illustrate the progress of the WHO's eradication campaign over the last 10 years. In dealing with part played by the aeroplane in the epidemiology of smallpox, attention is given to the high diffusion potential of the disease owing to increased air travel and the confluence of multi-ethnic and multi-national groups in airports. Prevention should thus be concentrated on airports as opposed to the rest of the country, and both aircrews and ground staff should be vaccinated. Stress indeed is laid on the need for vaccination and the search for further means of preventing its complications.", "contents": "[The role of aviation in the epidemiology of smallpox]. The structure and features of the smallpox virus are described and an account is given of the clinical picture of the disease. Tables and graphs are cited to illustrate the progress of the WHO's eradication campaign over the last 10 years. In dealing with part played by the aeroplane in the epidemiology of smallpox, attention is given to the high diffusion potential of the disease owing to increased air travel and the confluence of multi-ethnic and multi-national groups in airports. Prevention should thus be concentrated on airports as opposed to the rest of the country, and both aircrews and ground staff should be vaccinated. Stress indeed is laid on the need for vaccination and the search for further means of preventing its complications."}
{"id": "PMID:225701", "title": "Effects of isocaloric supplements of glucose or soyabean oil on lipids in tissues and plasma lipoproteins of starved and overfed chicks.", "content": "Chicks were overfed a basic diet supplemented isocalorically by soyabean oil or glucose 1, 2 and 10 days after 1 day of starvation. Carcass lipids resumed the prestarvation level 1 and 2 days after overfeeding with oil or glucose, respectively. After 10 days, an equal amount of lipid, mainly triglycerides, accumulated in the carcasses of both supplement groups. In the liver a transient accumulation of lipid was noticed in the oil-supplemented groups while a continuous increase was found in the glucose-supplemented ones. Hyperlipemia, due essentially to very low density lipoprotein (VLDL), was concomitant to liver lipid concentration. After 1 day, oil overfeeding raised plasma VLDL 6-fold, while the same level of VLDL was obtained within 2 days with glucose supplement. After 10 days, hyperlipemia was reduced in the oil-supplemented group, while it increased in the glucose-supplemented one. The fatty acid fluctuation caused by the treatments in liver lipids and plasma VLDL were grossly similar: the level of linoleic acid was reduced by glucose and increased by oil supplementation; the linoleic acid increase in VLDL preceeded that of liver lipids in the oil-supplemented groups. The results indicate a delayed transport of newly synthesized hepatic lipids in glucose-supplemented animals.", "contents": "Effects of isocaloric supplements of glucose or soyabean oil on lipids in tissues and plasma lipoproteins of starved and overfed chicks. Chicks were overfed a basic diet supplemented isocalorically by soyabean oil or glucose 1, 2 and 10 days after 1 day of starvation. Carcass lipids resumed the prestarvation level 1 and 2 days after overfeeding with oil or glucose, respectively. After 10 days, an equal amount of lipid, mainly triglycerides, accumulated in the carcasses of both supplement groups. In the liver a transient accumulation of lipid was noticed in the oil-supplemented groups while a continuous increase was found in the glucose-supplemented ones. Hyperlipemia, due essentially to very low density lipoprotein (VLDL), was concomitant to liver lipid concentration. After 1 day, oil overfeeding raised plasma VLDL 6-fold, while the same level of VLDL was obtained within 2 days with glucose supplement. After 10 days, hyperlipemia was reduced in the oil-supplemented group, while it increased in the glucose-supplemented one. The fatty acid fluctuation caused by the treatments in liver lipids and plasma VLDL were grossly similar: the level of linoleic acid was reduced by glucose and increased by oil supplementation; the linoleic acid increase in VLDL preceeded that of liver lipids in the oil-supplemented groups. The results indicate a delayed transport of newly synthesized hepatic lipids in glucose-supplemented animals."}
{"id": "PMID:225702", "title": "[Study of lipid metabolic coefficient K2 in patients with hyperlipoproteinemia type IV before and after reduction of triglyceride level by adapted diet therapy].", "content": "An intravenous fat tolerance test (IV FTT) was performed in a group of patients with type IV hyperlipoproteinemia before and after reduction of triglyceride level, the latter is obtained through a diet adapted to the nutritional sensitivity, body weight remaining constant. Before the diet the increase in cholesterol (CT) and triglycerides (TG) was related in both obese and non-obese patients to an increase in very-low-density lipoproteins (VLDL), while other lipoprotein fractions were not affected. In these patients, K2 is significantly lower than in controls whatever the nutritional sensitivity. However, K2 is lower in obese patients than in patients with normal weight, VLDL-CT and VLDL-TG are tremendously reduced by the relevant diet and K2 is constantly and significantly increased, although it does not reach a normal value in obese subjects. There is a highly significant correlation between VLDL-TG levels and K2 in obese and non-obese subjects. Several physiopathological explanations are discussed to account for the variation of K2 according to TG levels. The results obtained support the view that the K2 defect is secondary to the hyperlipoproteinemia.", "contents": "[Study of lipid metabolic coefficient K2 in patients with hyperlipoproteinemia type IV before and after reduction of triglyceride level by adapted diet therapy]. An intravenous fat tolerance test (IV FTT) was performed in a group of patients with type IV hyperlipoproteinemia before and after reduction of triglyceride level, the latter is obtained through a diet adapted to the nutritional sensitivity, body weight remaining constant. Before the diet the increase in cholesterol (CT) and triglycerides (TG) was related in both obese and non-obese patients to an increase in very-low-density lipoproteins (VLDL), while other lipoprotein fractions were not affected. In these patients, K2 is significantly lower than in controls whatever the nutritional sensitivity. However, K2 is lower in obese patients than in patients with normal weight, VLDL-CT and VLDL-TG are tremendously reduced by the relevant diet and K2 is constantly and significantly increased, although it does not reach a normal value in obese subjects. There is a highly significant correlation between VLDL-TG levels and K2 in obese and non-obese subjects. Several physiopathological explanations are discussed to account for the variation of K2 according to TG levels. The results obtained support the view that the K2 defect is secondary to the hyperlipoproteinemia."}
{"id": "PMID:225703", "title": "[Injection of mitochondria into oocytes and fertilized eggs].", "content": "The suspension of mitochondria isolated from the loach embryos or the frog heart were injected in the oocytes or fertilized eggs of the loach, newt, toad and frog in the amount roughly equivalent to the content of mitochondria in the egg. After the injection the oocytes did not differ during several days from the normal ones and the fertilized eggs of the loach, newt and South Afican clawed toad developed normally. The activity of cytochrome oxidase in the injected oocytes was kept at a somewhat higher level (1.4 to 1.9 vs 1.0 in the control) during several days. In the developing eggs the activity of cytochrome oxidase began to decrease from the blastula stage and attained rapidly the control level. The decrease of the enzyme activity is due to non-specific degradation of excessive mitochondria or to compensatory inactivation of the enzyme ensuring the maintenance of its normal activity during the development.", "contents": "[Injection of mitochondria into oocytes and fertilized eggs]. The suspension of mitochondria isolated from the loach embryos or the frog heart were injected in the oocytes or fertilized eggs of the loach, newt, toad and frog in the amount roughly equivalent to the content of mitochondria in the egg. After the injection the oocytes did not differ during several days from the normal ones and the fertilized eggs of the loach, newt and South Afican clawed toad developed normally. The activity of cytochrome oxidase in the injected oocytes was kept at a somewhat higher level (1.4 to 1.9 vs 1.0 in the control) during several days. In the developing eggs the activity of cytochrome oxidase began to decrease from the blastula stage and attained rapidly the control level. The decrease of the enzyme activity is due to non-specific degradation of excessive mitochondria or to compensatory inactivation of the enzyme ensuring the maintenance of its normal activity during the development."}
{"id": "PMID:225704", "title": "[Independence of the (NAD+):(NADH) ratio from the adenylic system in the liver cytoplasm of the developing chick embryo].", "content": "No dependence was found between the index of the adenylic system phosphorylated state (ATP) : (ADP) (HPO2-4), the ratios (ATP) : (ADP) and (ATP : (ADP + AMP), on one hand, and the ratio (NAD+) : (NADH) in the cytoplasm, on the other one. The maximum value of the ratio (ATP) : (ADP) (HPO2-4) was observed on the 17th day of development and correlated with the maximum rate of gluconeogenesis. The ratio (NAD+) : (NADH) in the cytoplasm suffered no changes until hatching and decreased twice thereafter.", "contents": "[Independence of the (NAD+):(NADH) ratio from the adenylic system in the liver cytoplasm of the developing chick embryo]. No dependence was found between the index of the adenylic system phosphorylated state (ATP) : (ADP) (HPO2-4), the ratios (ATP) : (ADP) and (ATP : (ADP + AMP), on one hand, and the ratio (NAD+) : (NADH) in the cytoplasm, on the other one. The maximum value of the ratio (ATP) : (ADP) (HPO2-4) was observed on the 17th day of development and correlated with the maximum rate of gluconeogenesis. The ratio (NAD+) : (NADH) in the cytoplasm suffered no changes until hatching and decreased twice thereafter."}
{"id": "PMID:225705", "title": "Oral cancer and herpes simplex virus--a review.", "content": "Numerous studies have suggested that patients with oral cancer have an increased immune response to herpes simplex virus. However, the number of cases has always been small, and essential controls have not always been included. Laboratory experiments have shown that herpes simplex virus can be carcinogenic or cocarcinogenic under certain circumstances and so must be considered as a possible etiologic agent in oral cancer. This article reviews past research and suggests priorities for future investigations.", "contents": "Oral cancer and herpes simplex virus--a review. Numerous studies have suggested that patients with oral cancer have an increased immune response to herpes simplex virus. However, the number of cases has always been small, and essential controls have not always been included. Laboratory experiments have shown that herpes simplex virus can be carcinogenic or cocarcinogenic under certain circumstances and so must be considered as a possible etiologic agent in oral cancer. This article reviews past research and suggests priorities for future investigations."}
{"id": "PMID:225706", "title": "Asymmetrical radical formation in D- and L-alanines irradiated with yttrium-90 beta-rays.", "content": "Radical formation in 90Y-beta-irradiated D- and L-alanines was studied using ESR. It was observed that the relative radical concentration by beta-irradiation was distinguishably (13.9-21.5%) more in D-alanine than in L-alanine. Discussion was made on the possible mechanisms for the observed results.", "contents": "Asymmetrical radical formation in D- and L-alanines irradiated with yttrium-90 beta-rays. Radical formation in 90Y-beta-irradiated D- and L-alanines was studied using ESR. It was observed that the relative radical concentration by beta-irradiation was distinguishably (13.9-21.5%) more in D-alanine than in L-alanine. Discussion was made on the possible mechanisms for the observed results."}
{"id": "PMID:225707", "title": "Localization of collagenase in chronically inflamed guinea pig temporal bone.", "content": "Bone destruction, commonly associated with chronic otitis media, requires collagen degradation. Collagenase, a neutral protease, appears to be an essential component in the process of collagen breakdown. Collagenase was identified within chronically inflamed and normal guinea pig temporal bones using an immunohistochemical technique with fluorescein isothyocyanate and peroxidase-antiperoxidase labels. Localization of the enzyme identifies sites of matrix resorption. Collagenase was found in osteoclasts, osteocytes, mononuclear inflammatory cells, and at resorbing margins. Inflammation increased the intracellular collagenase content of inflammatory bone osteocytes when compared to normal osteocytes using a microspectrofluorometer. It appears that the inflammatory process directly influences bone destruction through the action of mononuclear inflammatory cells and indirectly by stimulating bone cells to increase their proteolytic enzyme production.", "contents": "Localization of collagenase in chronically inflamed guinea pig temporal bone. Bone destruction, commonly associated with chronic otitis media, requires collagen degradation. Collagenase, a neutral protease, appears to be an essential component in the process of collagen breakdown. Collagenase was identified within chronically inflamed and normal guinea pig temporal bones using an immunohistochemical technique with fluorescein isothyocyanate and peroxidase-antiperoxidase labels. Localization of the enzyme identifies sites of matrix resorption. Collagenase was found in osteoclasts, osteocytes, mononuclear inflammatory cells, and at resorbing margins. Inflammation increased the intracellular collagenase content of inflammatory bone osteocytes when compared to normal osteocytes using a microspectrofluorometer. It appears that the inflammatory process directly influences bone destruction through the action of mononuclear inflammatory cells and indirectly by stimulating bone cells to increase their proteolytic enzyme production."}
{"id": "PMID:225710", "title": "Pathophysiology of Cushing's disease.", "content": "The term Cushing's disease is applied to those cases of Cushing's syndrome in which hypercortisolism is secondary to inappropriate secretion of ACTH by the pituitary. Studies on control of ACTH secretion in these patients reveal: (a) that the episodic secretion of ACTH is similar to the normal; however, frequency and amplitude of the secretory episodes lack the normal circadian rhythm; (b) that ACTH release can be stimulated by vasopressin and metyrapone in a normal or above-normal manner; and (c) that it can be suppressed by large doses of corticosteroids. When the dynamic aspects of the ACTH response to corticosteroid administration are studied, it appears that the normally negative differential feedback mechanism is converted into a positive one, whereas the delayed, integral mechanism is undisturbed. Patients with Cushing's disease in the presence of obvious pituitary tumors cannot be distinguished from those without pituitary tumors by studying only the pituitary function. All these and other well-known facts would favor the concept that ACTH secretion in Cushing's disease is under hypothalamic control whether or not a pituitary tumor is present. Moreover, there are observations that suggest that brain centers superior to the hypophysiotropic area of the hypothalamus are involved in the pathophysiology of Cushing's disease. This concept has led to the discovery of neurotropic drugs that are able to induce complete remission of Cushing's syndrome in a cerain percentage of patients. In some patients with severe psychiatric diseases, neuroendocrine abnormalities are present that resemble closely those characteristic for Cushing's disease. With the most refined neuroradiological methods, pituitary microadenomas are demonstrable in approximately 70% of patients with Cushing's disease, and this number compares well with those of earlier autopsy findings (70 to 80%). In a small number of patients (4 to 10%), these tumors are large and can easily be detected by standard roentgenograms of the head. Recent studies on the frequency of these large tumors do not support the hypothesis that adrenalectomy accelerates the progression of these tumors. In this case the term \"Nelson's syndrome\" would be uncessary. It is established that complete cure of Cushing's disease can be obtained in most patients with selective removal of a microadenoma from the pituitary gland. The current experience with this microsurgical procedure caused a renewed interest in Cushing's original suggestion that the disease is primarily a pituitary disorder. However, there are already a number of enigmatic observations. Possibly, the recent ultrastructural studies using immunocytochemical methods will resolve some of these problems. At this moment it is impossible to decide whether Cushing's disease is primarily a CNS or a pituitary disorder, when all arguments for one or the other hypothesis are taken into account...", "contents": "Pathophysiology of Cushing's disease. The term Cushing's disease is applied to those cases of Cushing's syndrome in which hypercortisolism is secondary to inappropriate secretion of ACTH by the pituitary. Studies on control of ACTH secretion in these patients reveal: (a) that the episodic secretion of ACTH is similar to the normal; however, frequency and amplitude of the secretory episodes lack the normal circadian rhythm; (b) that ACTH release can be stimulated by vasopressin and metyrapone in a normal or above-normal manner; and (c) that it can be suppressed by large doses of corticosteroids. When the dynamic aspects of the ACTH response to corticosteroid administration are studied, it appears that the normally negative differential feedback mechanism is converted into a positive one, whereas the delayed, integral mechanism is undisturbed. Patients with Cushing's disease in the presence of obvious pituitary tumors cannot be distinguished from those without pituitary tumors by studying only the pituitary function. All these and other well-known facts would favor the concept that ACTH secretion in Cushing's disease is under hypothalamic control whether or not a pituitary tumor is present. Moreover, there are observations that suggest that brain centers superior to the hypophysiotropic area of the hypothalamus are involved in the pathophysiology of Cushing's disease. This concept has led to the discovery of neurotropic drugs that are able to induce complete remission of Cushing's syndrome in a cerain percentage of patients. In some patients with severe psychiatric diseases, neuroendocrine abnormalities are present that resemble closely those characteristic for Cushing's disease. With the most refined neuroradiological methods, pituitary microadenomas are demonstrable in approximately 70% of patients with Cushing's disease, and this number compares well with those of earlier autopsy findings (70 to 80%). In a small number of patients (4 to 10%), these tumors are large and can easily be detected by standard roentgenograms of the head. Recent studies on the frequency of these large tumors do not support the hypothesis that adrenalectomy accelerates the progression of these tumors. In this case the term \"Nelson's syndrome\" would be uncessary. It is established that complete cure of Cushing's disease can be obtained in most patients with selective removal of a microadenoma from the pituitary gland. The current experience with this microsurgical procedure caused a renewed interest in Cushing's original suggestion that the disease is primarily a pituitary disorder. However, there are already a number of enigmatic observations. Possibly, the recent ultrastructural studies using immunocytochemical methods will resolve some of these problems. At this moment it is impossible to decide whether Cushing's disease is primarily a CNS or a pituitary disorder, when all arguments for one or the other hypothesis are taken into account..."}
{"id": "PMID:225708", "title": "Current evidence for the organic etiology of spastic dysphonia.", "content": "For over 100 years it has been universally assumed in the literature that spastic dysphonia is a functional or psychoneurotic voice disorder. In the last few years, new data have accumulated that support the concept that spastic dysphonia is caused by an organic, rather than a functional, abnormality. Histologic examination of segments of the recurrent laryngeal nerve removed from patients with spastic dysphonia has revealed myelin abnormalities in 30% of the nerves examined. Neurologic examination indicated brain stem or basal ganglia disturbances in some patients who had no apparent nerve disease.", "contents": "Current evidence for the organic etiology of spastic dysphonia. For over 100 years it has been universally assumed in the literature that spastic dysphonia is a functional or psychoneurotic voice disorder. In the last few years, new data have accumulated that support the concept that spastic dysphonia is caused by an organic, rather than a functional, abnormality. Histologic examination of segments of the recurrent laryngeal nerve removed from patients with spastic dysphonia has revealed myelin abnormalities in 30% of the nerves examined. Neurologic examination indicated brain stem or basal ganglia disturbances in some patients who had no apparent nerve disease."}
{"id": "PMID:225716", "title": "The biologic significance of the aldosterone concentration in saliva.", "content": "Salivary aldosterone measurements can be used to study aldosterone secretion and metabolism noninvasively. Salvia and plasma aldosterone concentration were highly correlated during all periods of study; during adrenocorticotrophic hormone (ACTH) administration, a relatively greater amount of aldosterone appeared in saliva; during dexamethasone administration, a relatively smaller amount of aldosterone appeared in saliva. As plasma cortisol increased with ACTH administration there was an increased relative amount of aldosterone in saliva. DOC (11-deoxycorticosterone) was found in saliva only during ACTH administration. Corticosterone was identified during baseline periods. Salivary aldosterone concentrations were independent of flow. The data indicate that saliva is an accessible bodily fluid which may be used to monitor the changes in nonprotein bound plasma steroid hormone concentration in children.", "contents": "The biologic significance of the aldosterone concentration in saliva. Salivary aldosterone measurements can be used to study aldosterone secretion and metabolism noninvasively. Salvia and plasma aldosterone concentration were highly correlated during all periods of study; during adrenocorticotrophic hormone (ACTH) administration, a relatively greater amount of aldosterone appeared in saliva; during dexamethasone administration, a relatively smaller amount of aldosterone appeared in saliva. As plasma cortisol increased with ACTH administration there was an increased relative amount of aldosterone in saliva. DOC (11-deoxycorticosterone) was found in saliva only during ACTH administration. Corticosterone was identified during baseline periods. Salivary aldosterone concentrations were independent of flow. The data indicate that saliva is an accessible bodily fluid which may be used to monitor the changes in nonprotein bound plasma steroid hormone concentration in children."}
{"id": "PMID:225717", "title": "Development aspects of renal beta-amino acid transport II. Ontogeny of uptake and efflux processes and effect of anoxia.", "content": "Renal cortex slices from newborn, 2-week, and 4-week-old Sprague-Dawley rats had reduced initial rates of taurine uptake compared to adult slices after short (less than 30 min) incubation periods. From birth onward, steady-state accumulation occurred by at least two sodium-dependent uptake systems. The first system had an \"apparent Km1\" = 0.1 mM and a Vmax varying from 1.8 to 5.1 mumoles/ml ICF/120 min at four ages. The second uptake mode had an apparent Km2 = 12-16 mM and a Vmax of 45 mumoles/ml ICF/120 min. Efflux of taurine was reduced in slices from younger animals possibly accounting for taurinuria. Only other beta-amino acids inhibited accumulation. Anoxia inhibited uptake at high concentration ( greater than 1.0 mM) at each age, but taurine accumulation at low concentrations ( less than 0.4 mM) was relatively protected from anoxia in neonatal ( less than 36 hr of age) tissue. Preincubation in taurine-free medium for 120 min enhanced low concentration, but not high concentration uptake in neonatal and 2-week slices. After preincubation in dibutyryl cyclic AMP (dbcAMP) enhanced uptake of taurine was found in adult cortex, but not in neonatal cortex. The ontogeny of renal taurine transport in cortex slices appeared to involve faster initial uptake rates and faster efflux as well as greater dependence on aerobic metabolism with maturation. Age-related differences in the response to preincubation and cyclic nucleotides were also indicative of maturation events in renal tubular amino acid transport.", "contents": "Development aspects of renal beta-amino acid transport II. Ontogeny of uptake and efflux processes and effect of anoxia. Renal cortex slices from newborn, 2-week, and 4-week-old Sprague-Dawley rats had reduced initial rates of taurine uptake compared to adult slices after short (less than 30 min) incubation periods. From birth onward, steady-state accumulation occurred by at least two sodium-dependent uptake systems. The first system had an \"apparent Km1\" = 0.1 mM and a Vmax varying from 1.8 to 5.1 mumoles/ml ICF/120 min at four ages. The second uptake mode had an apparent Km2 = 12-16 mM and a Vmax of 45 mumoles/ml ICF/120 min. Efflux of taurine was reduced in slices from younger animals possibly accounting for taurinuria. Only other beta-amino acids inhibited accumulation. Anoxia inhibited uptake at high concentration ( greater than 1.0 mM) at each age, but taurine accumulation at low concentrations ( less than 0.4 mM) was relatively protected from anoxia in neonatal ( less than 36 hr of age) tissue. Preincubation in taurine-free medium for 120 min enhanced low concentration, but not high concentration uptake in neonatal and 2-week slices. After preincubation in dibutyryl cyclic AMP (dbcAMP) enhanced uptake of taurine was found in adult cortex, but not in neonatal cortex. The ontogeny of renal taurine transport in cortex slices appeared to involve faster initial uptake rates and faster efflux as well as greater dependence on aerobic metabolism with maturation. Age-related differences in the response to preincubation and cyclic nucleotides were also indicative of maturation events in renal tubular amino acid transport."}
{"id": "PMID:225719", "title": "Effects of viral exposure of the two-cell mouse embryo on cleavage and blastocyst formation in vitro.", "content": "The effect of viral exposure of two-cell mouse embryos on their capacity to undergo subsequent cleavage and blastocyst formation in vitro was determined. Exposure to Coxsackie viruses B-4 and B-6, reovirus type 2, influenza virus type A, mouse cytomegalovirus, adenovirus type 5, and mouse adenovirus resulted in statistically significant inhibition of blastocyst formation. Development in vitro was unaffected by exposure to ECHO virus type 11, attenuated poliomyelitis virus type 2, parainfluenza virus type 1, mumps, rubella, and herpes simplex viruses types 1 and 2. Blastocyst formation was also unaffected by exposure of embryos to mouse interferon in a concentration 24 units/ml of culture fluid. Coxsackie virus B-4 was recovered from exposed embryos.", "contents": "Effects of viral exposure of the two-cell mouse embryo on cleavage and blastocyst formation in vitro. The effect of viral exposure of two-cell mouse embryos on their capacity to undergo subsequent cleavage and blastocyst formation in vitro was determined. Exposure to Coxsackie viruses B-4 and B-6, reovirus type 2, influenza virus type A, mouse cytomegalovirus, adenovirus type 5, and mouse adenovirus resulted in statistically significant inhibition of blastocyst formation. Development in vitro was unaffected by exposure to ECHO virus type 11, attenuated poliomyelitis virus type 2, parainfluenza virus type 1, mumps, rubella, and herpes simplex viruses types 1 and 2. Blastocyst formation was also unaffected by exposure of embryos to mouse interferon in a concentration 24 units/ml of culture fluid. Coxsackie virus B-4 was recovered from exposed embryos."}
{"id": "PMID:225723", "title": "Pain thresholds in rats during recovery from REM sleep deprivation.", "content": "Using 30 Sprague-Dawley female rats, threshold to pain was measured over the course of recovery from REM sleep deprivation. Relative to the untreated controls and to their own pretreatment thresholds, the REM-deprived animals showed significantly reduced pain thresholds which were still evident 96 hours after the termination of the REM deprivation. Possible implications of these data for research with analgesic drugs were noted.", "contents": "Pain thresholds in rats during recovery from REM sleep deprivation. Using 30 Sprague-Dawley female rats, threshold to pain was measured over the course of recovery from REM sleep deprivation. Relative to the untreated controls and to their own pretreatment thresholds, the REM-deprived animals showed significantly reduced pain thresholds which were still evident 96 hours after the termination of the REM deprivation. Possible implications of these data for research with analgesic drugs were noted."}
{"id": "PMID:225724", "title": "Corticosteroids and neuromuscular transmission: electrophysiological investigation of the effects of prednisolone on normal and anticholinesterase-treated neuromuscular junction.", "content": "The effect of prednisolone on indirectly stimulated rat muscle twitch was investigated at normal and prostigmine-treated neuromuscular junctions. In vivo, predenisolone up to 150 mg/kg body weight did not affect twitch contraction in normal animals. In neostigmine-pretreated animals, however, doses between 12.5 and 90 mg/kg could entirely abolish the anticholinesterase-induced twitch augmentation. In vitro, prednisolone produced a depressant effect on the twitch of a normal phrenic nerve diaphragm preparation which could amount to 20%. When the preparation was pretreated with neostigmine the augmented twitch could be depressed by 10(-3) to 10(-6) mol/l prednisolone to levels below the untreated control. Part of this effect is owing to a suppression of the neostigmine-induced, stimulus-bound repetitive firing of the motor nerve terminals, but to explain the full effect a further inhibitory action on neuromuscular transmission must be assumed. The latter could be accounted for by a depolarizing interaction of prednisolone and neostigmine on the nerve terminals resulting in conduction block. An action of prednisolone on postsynaptic receptors could also be considered. Such effects of the glucocorticoid might contribute to the exacerbation of muscular weakness occasionally observed in patients with myasthenia gravis at the beginning of steroid therapy.", "contents": "Corticosteroids and neuromuscular transmission: electrophysiological investigation of the effects of prednisolone on normal and anticholinesterase-treated neuromuscular junction. The effect of prednisolone on indirectly stimulated rat muscle twitch was investigated at normal and prostigmine-treated neuromuscular junctions. In vivo, predenisolone up to 150 mg/kg body weight did not affect twitch contraction in normal animals. In neostigmine-pretreated animals, however, doses between 12.5 and 90 mg/kg could entirely abolish the anticholinesterase-induced twitch augmentation. In vitro, prednisolone produced a depressant effect on the twitch of a normal phrenic nerve diaphragm preparation which could amount to 20%. When the preparation was pretreated with neostigmine the augmented twitch could be depressed by 10(-3) to 10(-6) mol/l prednisolone to levels below the untreated control. Part of this effect is owing to a suppression of the neostigmine-induced, stimulus-bound repetitive firing of the motor nerve terminals, but to explain the full effect a further inhibitory action on neuromuscular transmission must be assumed. The latter could be accounted for by a depolarizing interaction of prednisolone and neostigmine on the nerve terminals resulting in conduction block. An action of prednisolone on postsynaptic receptors could also be considered. Such effects of the glucocorticoid might contribute to the exacerbation of muscular weakness occasionally observed in patients with myasthenia gravis at the beginning of steroid therapy."}
{"id": "PMID:225725", "title": "Effect of physical training on the development of hypertension in the spontaneously hypertensive rat.", "content": "The effect of chronic physical exercise on the development of hypertension was measured in spontaneously hypertensive rats (SHR) and their progenitor normotensive wistar-kyoto controls (WK). Starting 4--5 weeks after birth groups of rats were subjected to swimming exercise 1 h x day-1, 4 days x week-1 for a total period of 11 weeks. Control rats were handled daily without exercise. Both in trained SHR and WK a significant delay in increase in body weight was observed. Physical training caused a small, but significant (P less than 0.001) reduction in systolic blood pressure of SHR, whereas it did not affect blood pressure in WK. Heart rate was significantly (P less than 0.001) lower in both trained SHR and WK than in their non-trained controls. At the end of the training period the degree of training was tested by measuring muscle cytochrome oxidase activity and relative heart weight. Cytochrome oxidase activity in gastrocnemius muscle was higher in the trained animals, although the difference was only significant (P less than 0.05) for WK. Training also caused a significant (P less than 0.01) increase in the ratio heart weight to body weight in WK. Both trained and non-trained SHR have a ca. 25% higher relative heart weight than WK controls. SHR hearts did not further hypertrophy as a consequence of physical exercise. These data indicate that swim training induces a trained state in both SHR and WK. Moreover, this form of training causes a slight, but significant attenuation of the development of hypertension in SHR.", "contents": "Effect of physical training on the development of hypertension in the spontaneously hypertensive rat. The effect of chronic physical exercise on the development of hypertension was measured in spontaneously hypertensive rats (SHR) and their progenitor normotensive wistar-kyoto controls (WK). Starting 4--5 weeks after birth groups of rats were subjected to swimming exercise 1 h x day-1, 4 days x week-1 for a total period of 11 weeks. Control rats were handled daily without exercise. Both in trained SHR and WK a significant delay in increase in body weight was observed. Physical training caused a small, but significant (P less than 0.001) reduction in systolic blood pressure of SHR, whereas it did not affect blood pressure in WK. Heart rate was significantly (P less than 0.001) lower in both trained SHR and WK than in their non-trained controls. At the end of the training period the degree of training was tested by measuring muscle cytochrome oxidase activity and relative heart weight. Cytochrome oxidase activity in gastrocnemius muscle was higher in the trained animals, although the difference was only significant (P less than 0.05) for WK. Training also caused a significant (P less than 0.01) increase in the ratio heart weight to body weight in WK. Both trained and non-trained SHR have a ca. 25% higher relative heart weight than WK controls. SHR hearts did not further hypertrophy as a consequence of physical exercise. These data indicate that swim training induces a trained state in both SHR and WK. Moreover, this form of training causes a slight, but significant attenuation of the development of hypertension in SHR."}
{"id": "PMID:225726", "title": "Studies on the synaptic interconnection between bulbar respiratory neurones of cats.", "content": "In cats anaesthetized with pentobarbital, medullary respiratory neurones of both dorsal and ventral populations were recorded intracellularly with 1 mol.l-1 KCl-electrodes. The neurones were classified according to the projection of their axons to the spinal cord (bulbospinal neurones) or to the vagal nerves (vagal neurones). Those neurones which could not be activated antidromically (NAA-neurones) by either procedure were subdivided into (inspiratory) R beta-neurones, which were monosynaptically excited by lung stretch receptor afferents, and into inspiratory and expiratory NAA-neurones, which did not receive a direct synaptic input, from these afferents. All types of neurone investigated revealed postsynaptic activity during both inspiration and expiration. The periods when synaptic activity was minimal were the periods of transition between respiratory phases. The input resistance of most respiratory neurones varied in parallel with the respiratory cycle. A drastic fall of the input resistance during expiration was observed in R beta-neurones and in some inspiratory vagal neurones. This was not seen in inspiratory bulbospinal neurones. In stable intracellular recordings, periodic postsynaptic inhibition was demonstrated in 52 of 53 respiratory neurones by IPSP reversal following chloride injection. Maximal membrane potential then was generally reached during one of the periods of respiratory phase transition. Reasons for the failure of others to demonstrate these IPSPs are presented and discrepancies between other findings and these are discussed. It is concluded that reciprocal inhibition between bulbar respiratory neurones does exist and is a general phenomenon. It is argued that reciprocal inhibition is the fundamental mechanism underlying respiratory gating of afferent inputs. The probable existence of recurrent inhibition is inferred from the changes in the pattern of membrane depolarization during the active period of neurones.", "contents": "Studies on the synaptic interconnection between bulbar respiratory neurones of cats. In cats anaesthetized with pentobarbital, medullary respiratory neurones of both dorsal and ventral populations were recorded intracellularly with 1 mol.l-1 KCl-electrodes. The neurones were classified according to the projection of their axons to the spinal cord (bulbospinal neurones) or to the vagal nerves (vagal neurones). Those neurones which could not be activated antidromically (NAA-neurones) by either procedure were subdivided into (inspiratory) R beta-neurones, which were monosynaptically excited by lung stretch receptor afferents, and into inspiratory and expiratory NAA-neurones, which did not receive a direct synaptic input, from these afferents. All types of neurone investigated revealed postsynaptic activity during both inspiration and expiration. The periods when synaptic activity was minimal were the periods of transition between respiratory phases. The input resistance of most respiratory neurones varied in parallel with the respiratory cycle. A drastic fall of the input resistance during expiration was observed in R beta-neurones and in some inspiratory vagal neurones. This was not seen in inspiratory bulbospinal neurones. In stable intracellular recordings, periodic postsynaptic inhibition was demonstrated in 52 of 53 respiratory neurones by IPSP reversal following chloride injection. Maximal membrane potential then was generally reached during one of the periods of respiratory phase transition. Reasons for the failure of others to demonstrate these IPSPs are presented and discrepancies between other findings and these are discussed. It is concluded that reciprocal inhibition between bulbar respiratory neurones does exist and is a general phenomenon. It is argued that reciprocal inhibition is the fundamental mechanism underlying respiratory gating of afferent inputs. The probable existence of recurrent inhibition is inferred from the changes in the pattern of membrane depolarization during the active period of neurones."}
{"id": "PMID:225727", "title": "[Pesticide residues in feed-stuffs in Sweden (author's transl)].", "content": "The occurrence of pesticide residues was studied in samples of feed-stuffs produced in Sweden or imported to Sweden during the years 1972--1976. In all, 278 samples representing 37 types of feed-stuffs (components, as well as finished feeds) and 18 countries were analyzed. Residues of chlorinated hydrocarbon pesticides and PCBs were looked for in 224 samples, mostly feed components. The analytical method used involved solvent extraction, florisil-column clean-up, thinlayer chromatographic separation and gas-chromatographic determination. Chlorinated hydrocarbons were found in several samples. DDT and its transformation products were detected in 66 samples (29.5%), lindane in 44 (19.5%), PCBs in 25 (11.2%), alpha-BHC in 22 (9.8%), beta-BHC in 11 (4.9%) and dieldrin in 9 (4.0%). The levels were usually low (Table I). The chloropesticides occurred most frequently and at the highest levels in feed-stuffs of animal origin and in imported oil-feeds. In 25 of the samples the contents of sigmaDDT exceeded the maximum limit accepted by the National (Swedish) Food Administration for grain and bran intended for human consumption (0.05 mg/kg, Talbe IV). The highest residue level of sigmaDDT (0.66 mg/kg) was encountered in a sample of fish meal. The PCB levels found did not exceed the temporary tolerance established by FDA (1973) for finished animal feeds (0.2 mg/kg). One hundred and seven samples were analyzed for phenoxy acid residues using a thin-layer chromatographic and gas-chromatographic technique. Phenoxy acids were detected in only 2 of 62 randomly selected feed samples (0.05 and 0.2 mg/kg, respectively). The residue limit established by the National Food Administration for 2,4-D and MCPA in grain and bran intended for human consumption is 0.1 mg/kg. Fortyfour samples of feeds were submitted because of suspected phenoxy acid contamination. In 12 of the samples phenoxy acid residues were found. The highest level (3.5 mg/kg, MCPA) was observed in a sample of accidentally contaminated molasses. Considering the apparently low level of contamination of Swedish grain with chloropesticides, PCBs and phenoxy acids and the dilution on compounding feed-stuffs of animal origin and oil-feeds, only very low pesticide residue levels can be expected in Swedish finished animal feeds.", "contents": "[Pesticide residues in feed-stuffs in Sweden (author's transl)]. The occurrence of pesticide residues was studied in samples of feed-stuffs produced in Sweden or imported to Sweden during the years 1972--1976. In all, 278 samples representing 37 types of feed-stuffs (components, as well as finished feeds) and 18 countries were analyzed. Residues of chlorinated hydrocarbon pesticides and PCBs were looked for in 224 samples, mostly feed components. The analytical method used involved solvent extraction, florisil-column clean-up, thinlayer chromatographic separation and gas-chromatographic determination. Chlorinated hydrocarbons were found in several samples. DDT and its transformation products were detected in 66 samples (29.5%), lindane in 44 (19.5%), PCBs in 25 (11.2%), alpha-BHC in 22 (9.8%), beta-BHC in 11 (4.9%) and dieldrin in 9 (4.0%). The levels were usually low (Table I). The chloropesticides occurred most frequently and at the highest levels in feed-stuffs of animal origin and in imported oil-feeds. In 25 of the samples the contents of sigmaDDT exceeded the maximum limit accepted by the National (Swedish) Food Administration for grain and bran intended for human consumption (0.05 mg/kg, Talbe IV). The highest residue level of sigmaDDT (0.66 mg/kg) was encountered in a sample of fish meal. The PCB levels found did not exceed the temporary tolerance established by FDA (1973) for finished animal feeds (0.2 mg/kg). One hundred and seven samples were analyzed for phenoxy acid residues using a thin-layer chromatographic and gas-chromatographic technique. Phenoxy acids were detected in only 2 of 62 randomly selected feed samples (0.05 and 0.2 mg/kg, respectively). The residue limit established by the National Food Administration for 2,4-D and MCPA in grain and bran intended for human consumption is 0.1 mg/kg. Fortyfour samples of feeds were submitted because of suspected phenoxy acid contamination. In 12 of the samples phenoxy acid residues were found. The highest level (3.5 mg/kg, MCPA) was observed in a sample of accidentally contaminated molasses. Considering the apparently low level of contamination of Swedish grain with chloropesticides, PCBs and phenoxy acids and the dilution on compounding feed-stuffs of animal origin and oil-feeds, only very low pesticide residue levels can be expected in Swedish finished animal feeds."}
{"id": "PMID:225729", "title": "BKV splice sequences based on analysis of preferred donor and acceptor sites.", "content": "We have determined the DNA sequences which correspond to the splicing regions in the transcripts of human papovavirus BKV, an evolutionary variant of SV40. To precisely localize the excision points in the BKV sequence, we have conducted a preliminary analysis of numerous viral and eukaryotic splice site sequences. This analysis suggests that the preferred sequence for the donor site belongs to at least one of four groups: Pu\u2193GTAxG, Pu\u2193GTAxxT, Pu\u2193GTxxGT, Pu\u2193GTxAG (\u2193 = the cleavage site). These four groups derive from the two basic sequences, Pu\u2193GTxxG and Pu\u2193GTA. An optimal donor site might be: AG\u2193GTAAGT. The preferred sequence for the acceptor site is of the form PyPyxPyAG\u2193; no dinucleotide AG occurs within 13 nucleotides prior to the terminal AG of the 3' end of the intervening sequences. As we have found in this study of BKV splice sites, the sequences for the preferred donor and acceptor sites provide predictive value in localizing RNA splice points when the DNA sequence is known.", "contents": "BKV splice sequences based on analysis of preferred donor and acceptor sites. We have determined the DNA sequences which correspond to the splicing regions in the transcripts of human papovavirus BKV, an evolutionary variant of SV40. To precisely localize the excision points in the BKV sequence, we have conducted a preliminary analysis of numerous viral and eukaryotic splice site sequences. This analysis suggests that the preferred sequence for the donor site belongs to at least one of four groups: Pu\u2193GTAxG, Pu\u2193GTAxxT, Pu\u2193GTxxGT, Pu\u2193GTxAG (\u2193 = the cleavage site). These four groups derive from the two basic sequences, Pu\u2193GTxxG and Pu\u2193GTA. An optimal donor site might be: AG\u2193GTAAGT. The preferred sequence for the acceptor site is of the form PyPyxPyAG\u2193; no dinucleotide AG occurs within 13 nucleotides prior to the terminal AG of the 3' end of the intervening sequences. As we have found in this study of BKV splice sites, the sequences for the preferred donor and acceptor sites provide predictive value in localizing RNA splice points when the DNA sequence is known."}
{"id": "PMID:225734", "title": "Weight and skeletal maturation - a study of radiological and chronological age in an anorexia nervosa population.", "content": "The carpal bones of 18 anorexia nervosa patients were radiographed and the X-ray age assessed by 2 different standard methods. The study demonstrates that skeletal development in anorexia nervosa patients is delayed such that there is no association between radiological assessment of age and chronological age. It is strongly suggested that bony development actually ceases when body weight falls sufficiently to stop menstruation. There was a highly significant (P = 0.001) linear relationship between radiological age and the sum of the age of onset of the illness plus any period(s) of re-feeding. Weight gain seems to re-kindle the bone maturing mechanisms: the role of weight thresholds and associated hormone activity being discussed. The findings of this study strongly support the existing evidence that the anorexia nervosa patient is biologically and psychologically immature.", "contents": "Weight and skeletal maturation - a study of radiological and chronological age in an anorexia nervosa population. The carpal bones of 18 anorexia nervosa patients were radiographed and the X-ray age assessed by 2 different standard methods. The study demonstrates that skeletal development in anorexia nervosa patients is delayed such that there is no association between radiological assessment of age and chronological age. It is strongly suggested that bony development actually ceases when body weight falls sufficiently to stop menstruation. There was a highly significant (P = 0.001) linear relationship between radiological age and the sum of the age of onset of the illness plus any period(s) of re-feeding. Weight gain seems to re-kindle the bone maturing mechanisms: the role of weight thresholds and associated hormone activity being discussed. The findings of this study strongly support the existing evidence that the anorexia nervosa patient is biologically and psychologically immature."}
{"id": "PMID:225735", "title": "Neutrophil function and diagnosis of pre-leukaemic states.", "content": "Haemopoietic dysplasia is a condition which often precedes the development of acute non-lymphocytic leukaemia. Before this event, however, patients are at risk from severe infections even in the absence of neutropenia. This paper describes 3 patients with haemopoietic dysplasias in whom neutrophil microbicidal activity was deficient in vitro. The important abnormality appeared to be defective release of myeloperoxidase into the phagocytic vacuole. Two of these patients suffered from numerous baterial infections.", "contents": "Neutrophil function and diagnosis of pre-leukaemic states. Haemopoietic dysplasia is a condition which often precedes the development of acute non-lymphocytic leukaemia. Before this event, however, patients are at risk from severe infections even in the absence of neutropenia. This paper describes 3 patients with haemopoietic dysplasias in whom neutrophil microbicidal activity was deficient in vitro. The important abnormality appeared to be defective release of myeloperoxidase into the phagocytic vacuole. Two of these patients suffered from numerous baterial infections."}
{"id": "PMID:225736", "title": "Trigeminal neuropathy as the presenting symptom of systemic sclerosis.", "content": "Three cases of systemic sclerosis in which trigeminal neuropathy was the presenting symptom are described. All 3 patients had progressive diseases and 2 died from its complications. In each case extensive neurological investigation was undertaken before the disease was recognized and it is suggested that earlier recognition of the systemic sclerosis might obviate the need for this. Trigeminal neuropathy in systemic sclerosis was associated with a poor prognosis in 2 of the patients.", "contents": "Trigeminal neuropathy as the presenting symptom of systemic sclerosis. Three cases of systemic sclerosis in which trigeminal neuropathy was the presenting symptom are described. All 3 patients had progressive diseases and 2 died from its complications. In each case extensive neurological investigation was undertaken before the disease was recognized and it is suggested that earlier recognition of the systemic sclerosis might obviate the need for this. Trigeminal neuropathy in systemic sclerosis was associated with a poor prognosis in 2 of the patients."}
{"id": "PMID:225733", "title": "Stimulatory effect of chlordiazepoxide on locomotor activity in mice: importance of noradrenergic transmission.", "content": "Chlorodiazepoxide (CDP) produces stimulation of the locomotor activity of CD-1 and DBA/2 mice. This effect is strongly pronounced at the commencement of the testing session, and it is followed by a decline of the locomotor activity. The drugs impairing noradrenergic transmission: reserpine, clonidine and alpha-methyltyrosine, depressed or abolished the stimulatory effect of CDP; clonidine, in addition antagonized the subsequent decline of the locomotor activity in CDP-treated mice. Mice receiving reserpine subchronically (in the dose of 0.5 mg/kg daily for 3 days) displayed either motor depression or hypermotility. In approx. 50% of subchronically reserpinized mice CDP produced a strong hypermotility, lasting for at least 1 hr. It can be concluded that a noradrenergic mechanism is involved in the stimulatory effect of CDP on exploratory locomotor activity in mice, and that there exist two distinct subpopulations within the CD-1 strain, reacting differently to chronic reserpine treatment.", "contents": "Stimulatory effect of chlordiazepoxide on locomotor activity in mice: importance of noradrenergic transmission. Chlorodiazepoxide (CDP) produces stimulation of the locomotor activity of CD-1 and DBA/2 mice. This effect is strongly pronounced at the commencement of the testing session, and it is followed by a decline of the locomotor activity. The drugs impairing noradrenergic transmission: reserpine, clonidine and alpha-methyltyrosine, depressed or abolished the stimulatory effect of CDP; clonidine, in addition antagonized the subsequent decline of the locomotor activity in CDP-treated mice. Mice receiving reserpine subchronically (in the dose of 0.5 mg/kg daily for 3 days) displayed either motor depression or hypermotility. In approx. 50% of subchronically reserpinized mice CDP produced a strong hypermotility, lasting for at least 1 hr. It can be concluded that a noradrenergic mechanism is involved in the stimulatory effect of CDP on exploratory locomotor activity in mice, and that there exist two distinct subpopulations within the CD-1 strain, reacting differently to chronic reserpine treatment."}
{"id": "PMID:225737", "title": "Severe orthostatic hypotension associated with carcinoma of the bronchus.", "content": "A patient is described who had severe orthostatic hypotension. An account is given of his treatment with a monoamine oxidase inhibitor and tyramine. At post-mortem, 8 months after the illness began, a small oat cell carcinoma of the bronchus was found. It is suggested that the orthostatic hypotension was a nonmetastatic manifestation of the underlying carcinoma.", "contents": "Severe orthostatic hypotension associated with carcinoma of the bronchus. A patient is described who had severe orthostatic hypotension. An account is given of his treatment with a monoamine oxidase inhibitor and tyramine. At post-mortem, 8 months after the illness began, a small oat cell carcinoma of the bronchus was found. It is suggested that the orthostatic hypotension was a nonmetastatic manifestation of the underlying carcinoma."}
{"id": "PMID:225738", "title": "Bilateral sixth cranial nerve palsy in infectious mononucleosis.", "content": "A 15-year-old girl who presented with a bilateral sixth nerve palsy caused by infectious mononucleosis is described. The neurological presentation of infectious mononucleosis is discussed.", "contents": "Bilateral sixth cranial nerve palsy in infectious mononucleosis. A 15-year-old girl who presented with a bilateral sixth nerve palsy caused by infectious mononucleosis is described. The neurological presentation of infectious mononucleosis is discussed."}
{"id": "PMID:225744", "title": "Cerebral blood flow after treatment with ORG-2766, a potent analog of ACTH 4--9.", "content": "Regional cerebral blood flows (rCBF) were measured in conscious, male rats at 10, 30, 60 min and 24 hr after intravenous administration of a potent, behaviorally active analog of ACTH/MSH 4--9 (ORG-2766). Flows in the basal ganglia, hippocampus, septal area and frontal cortex were depressed significantly throughout the 60 min postinjection period. HYpothalamic and parietal flows were depressed at 10 and 30 min, but recovered by 60 min, whereas flow to the cerebellum was depressed between 30 and 60 min postinjection. The least changed and therefore relatively better perfused area throughout the first 60 min period was the occipital cortex. By contrast, at 24 hr, when perfusion of all brain regions had returned to near control levels, flow to the occipital cortex was elevated. During the first hour after treatment with either ORG-2766 or alphaMSH the patterns of regional circulation in the brain were qualitatively the same. The data suggest that ORG-2766 and, probably, alpha MSH trigger serially linked neurophysiologic changes in the brain lasting at least 24 hr, which organize the behavioral actions of this class of peptides on memory and attentional processes.", "contents": "Cerebral blood flow after treatment with ORG-2766, a potent analog of ACTH 4--9. Regional cerebral blood flows (rCBF) were measured in conscious, male rats at 10, 30, 60 min and 24 hr after intravenous administration of a potent, behaviorally active analog of ACTH/MSH 4--9 (ORG-2766). Flows in the basal ganglia, hippocampus, septal area and frontal cortex were depressed significantly throughout the 60 min postinjection period. HYpothalamic and parietal flows were depressed at 10 and 30 min, but recovered by 60 min, whereas flow to the cerebellum was depressed between 30 and 60 min postinjection. The least changed and therefore relatively better perfused area throughout the first 60 min period was the occipital cortex. By contrast, at 24 hr, when perfusion of all brain regions had returned to near control levels, flow to the occipital cortex was elevated. During the first hour after treatment with either ORG-2766 or alphaMSH the patterns of regional circulation in the brain were qualitatively the same. The data suggest that ORG-2766 and, probably, alpha MSH trigger serially linked neurophysiologic changes in the brain lasting at least 24 hr, which organize the behavioral actions of this class of peptides on memory and attentional processes."}
{"id": "PMID:225749", "title": "A collagen film for microdetermination of collagenase activity.", "content": "A simple, rapid, sensitive, and specific film assay for collagenase activity employing a glass-supported, reconstituted collagen gel is described. Digestion of the collagen film results in sharply defined zones of lysis detectable by staining with Coomassie blue. The assay is semiquantitative and suitable for micro enzyme determination in biological fluids.", "contents": "A collagen film for microdetermination of collagenase activity. A simple, rapid, sensitive, and specific film assay for collagenase activity employing a glass-supported, reconstituted collagen gel is described. Digestion of the collagen film results in sharply defined zones of lysis detectable by staining with Coomassie blue. The assay is semiquantitative and suitable for micro enzyme determination in biological fluids."}
{"id": "PMID:225756", "title": "[Computerized tomography in the evaluation (author's transl)].", "content": "CT can clearly demonstrate dilation of intra- and extra-hepatic bile ducts due to mechanical obstruction. Note is made that the intrahepatic bile must not necessarily participate in dilation in obstructive jaundice. The cause in 27 cases observed in our institutions was as follows: 16 pancreatic tumors; 1 stone; 2 extrahepatic bile duct obstructions; 4 liver lesions (tumor and cirrhosis) and 4 with cause unknown. Furthermore, CT is helpful in the evaluation of hepatogenic non-obstructive jaundice such as due to primary liver cell carcinoma (hepatoma), metastases to the liver and advanced cirrhosis of the liver. The value of CT in the evaluation of different types of cholestasis is demonstrated by several exemplary cases; and the problems of differential diagnosis are pointed out.", "contents": "[Computerized tomography in the evaluation (author's transl)]. CT can clearly demonstrate dilation of intra- and extra-hepatic bile ducts due to mechanical obstruction. Note is made that the intrahepatic bile must not necessarily participate in dilation in obstructive jaundice. The cause in 27 cases observed in our institutions was as follows: 16 pancreatic tumors; 1 stone; 2 extrahepatic bile duct obstructions; 4 liver lesions (tumor and cirrhosis) and 4 with cause unknown. Furthermore, CT is helpful in the evaluation of hepatogenic non-obstructive jaundice such as due to primary liver cell carcinoma (hepatoma), metastases to the liver and advanced cirrhosis of the liver. The value of CT in the evaluation of different types of cholestasis is demonstrated by several exemplary cases; and the problems of differential diagnosis are pointed out."}
{"id": "PMID:225757", "title": "[Percutaneous transhepatic procedures for diagnosis and therapy in obstructive jaundice (author's transl)].", "content": "The techniques of percutaneous transhepatic cholangiography, intubation of the bile ducts for external and internal drainage, application of endoprostheses and removal of biliary tract stones as performed at the Department of Diagnostic Radiology in Lund, Sweden, are described. A flow diagram for diagnostic and therapeutic procedures in patients with obstructive jaundice is discussed.", "contents": "[Percutaneous transhepatic procedures for diagnosis and therapy in obstructive jaundice (author's transl)]. The techniques of percutaneous transhepatic cholangiography, intubation of the bile ducts for external and internal drainage, application of endoprostheses and removal of biliary tract stones as performed at the Department of Diagnostic Radiology in Lund, Sweden, are described. A flow diagram for diagnostic and therapeutic procedures in patients with obstructive jaundice is discussed."}
{"id": "PMID:225765", "title": "[Kinetic mechanism of chicken liver mitochondrial malatedehydrogenase (author's transl)].", "content": "Kinetic mechanism of chicken liver mitochondrial malatedehydrogenase is established from the initial reaction rates and reaction product inhibition. The results obtained in the reduction of NAD+ (pH 10) allow the formulation of an ordered bi-bi mechanism in which the coenzyme is the first substrate added to the enzyme. Inhibition by the reaction products and by the excess of the very substrates, reveals the formation of the E-oxaloacetate; E-L-malate; E-NAD+-oxaloacetate; E.NAD+-NADH; E-NADH-NADH and E-NAD-NAD+ abortive complexes, the significance of which may be checked under defined experimental conditions. Enzyme inhibition by ATP, ADP and AMP in the reduction of NAD+ (pH10), accords with the proposed mechanism and proceeds via formation of the E-nucleotide and E-NAD+-nucleotide inactive complexes.", "contents": "[Kinetic mechanism of chicken liver mitochondrial malatedehydrogenase (author's transl)]. Kinetic mechanism of chicken liver mitochondrial malatedehydrogenase is established from the initial reaction rates and reaction product inhibition. The results obtained in the reduction of NAD+ (pH 10) allow the formulation of an ordered bi-bi mechanism in which the coenzyme is the first substrate added to the enzyme. Inhibition by the reaction products and by the excess of the very substrates, reveals the formation of the E-oxaloacetate; E-L-malate; E-NAD+-oxaloacetate; E.NAD+-NADH; E-NADH-NADH and E-NAD-NAD+ abortive complexes, the significance of which may be checked under defined experimental conditions. Enzyme inhibition by ATP, ADP and AMP in the reduction of NAD+ (pH10), accords with the proposed mechanism and proceeds via formation of the E-nucleotide and E-NAD+-nucleotide inactive complexes."}
{"id": "PMID:225766", "title": "[The geriatric day hospital (author's transl)].", "content": "The author surveys the development of geriatric care in Great Britain and describes the relationship between geriatric medicine and psychogeriatrics. Both specialties have evolved within the system of progressive patient-care day hospitals. The responsible ministry lays down a norm of two places in both the psychogeriatric unit and geriatric days hospitals to every one thousand people aged 65 and over. The author presents the range of functions of the geriatric day hospital as well as its role within the framework of facilities caring for the aged.", "contents": "[The geriatric day hospital (author's transl)]. The author surveys the development of geriatric care in Great Britain and describes the relationship between geriatric medicine and psychogeriatrics. Both specialties have evolved within the system of progressive patient-care day hospitals. The responsible ministry lays down a norm of two places in both the psychogeriatric unit and geriatric days hospitals to every one thousand people aged 65 and over. The author presents the range of functions of the geriatric day hospital as well as its role within the framework of facilities caring for the aged."}
{"id": "PMID:225767", "title": "[Experimental acceleration of fracture repair by biochemical media (author's transl)].", "content": "The influence of calcitonine, amino acids, ribonucleid acids, kallikrein, growth hormone, and cyclic adenosine 3'5' monophosphate on fracture repair was tested in rabbits. To obtain an objective measurement of callus stability the bones were bent mechanically. The force applied and the degree of bending were recorded continuously. The slope of the curve was taken as a parameter of callus stability. In the series with calcitonine no influence on fracture healing was found. Injections of ribonucleic acids, amino acids, kallidrein, and growth hormone demonstrated a limited effect on bone repair. Callus formation was stimulated by adenosine 3'5' monophosphate. Optimal results were achieved by a combination of adenosine 3'5' monophosphate, amino acids, ribonucleic acids, and kallikrein.", "contents": "[Experimental acceleration of fracture repair by biochemical media (author's transl)]. The influence of calcitonine, amino acids, ribonucleid acids, kallikrein, growth hormone, and cyclic adenosine 3'5' monophosphate on fracture repair was tested in rabbits. To obtain an objective measurement of callus stability the bones were bent mechanically. The force applied and the degree of bending were recorded continuously. The slope of the curve was taken as a parameter of callus stability. In the series with calcitonine no influence on fracture healing was found. Injections of ribonucleic acids, amino acids, kallidrein, and growth hormone demonstrated a limited effect on bone repair. Callus formation was stimulated by adenosine 3'5' monophosphate. Optimal results were achieved by a combination of adenosine 3'5' monophosphate, amino acids, ribonucleic acids, and kallikrein."}
{"id": "PMID:225781", "title": "[Contribution of dynamic isotopic tests in the study of algodystrophies].", "content": "The authors studied 20 patients suffering from algodystrophy (23 localizations) by triple scintigraphy with technetium, using pyrophosphate to study the importance of bone changes, marked red blood cells to measure the vascular volume, and pertechnetate to measure the interstitial compartment. These tests were done on the average 1.4 months after the outset of the disease. This work made it possible to demonstrate in the algodystrophy: a pronounced bone hyperfixation that was uneven according to the patients; a frank increase in the vascular volume, notably on the capillary level, and a reduction of the circulatory output (calculated on 4 distal localizations), and an increase of the interstitial compartment higher than that of the vascular volume and corresponding to the edema. These results demonstrate a circulatory stasis. In 4 patients treatment with calcitonine reduced the vascular volume but not the bone hyperfixation. In 1 patient, treatment with pindolol reduced the bone hyperfixation and the vascular volume. The authors underline the advantage of such methods in creating a better knowledge of the physiopathology of algodystrophies and effective means of treating them.", "contents": "[Contribution of dynamic isotopic tests in the study of algodystrophies]. The authors studied 20 patients suffering from algodystrophy (23 localizations) by triple scintigraphy with technetium, using pyrophosphate to study the importance of bone changes, marked red blood cells to measure the vascular volume, and pertechnetate to measure the interstitial compartment. These tests were done on the average 1.4 months after the outset of the disease. This work made it possible to demonstrate in the algodystrophy: a pronounced bone hyperfixation that was uneven according to the patients; a frank increase in the vascular volume, notably on the capillary level, and a reduction of the circulatory output (calculated on 4 distal localizations), and an increase of the interstitial compartment higher than that of the vascular volume and corresponding to the edema. These results demonstrate a circulatory stasis. In 4 patients treatment with calcitonine reduced the vascular volume but not the bone hyperfixation. In 1 patient, treatment with pindolol reduced the bone hyperfixation and the vascular volume. The authors underline the advantage of such methods in creating a better knowledge of the physiopathology of algodystrophies and effective means of treating them."}
{"id": "PMID:225782", "title": "Angiographic localization of beta cell tumours.", "content": "Angiography was carried out on 28 patients by which a beta cell tumour was verified in 21. One case was excluded as no final diagnosis was established. Angiography correctly localized 14/17 adenomas (82%) and 3/4 carcinomas (75%), in total 17/21 tumours (81%). The adenomas were equally distributed throughout the pancreas. Three false negative diagnoses included an adenoma in the head of pancreas seen in retrospect, a hypovascular adenoma in the head of pancreas and an adenoma in the tail of pancreas which probably was hidden by the spleen. All carcinomas were located in the body and tail of pancreas. Metastases to the liver were demonstrated in two cases, although present in all. One carcinoma was not distinguished from superimposed metastases in the left lobe of the liver. A false positive diagnosis was reported in 3/7 cases (57%). One resulted from accumulation of contrast in the duodenal mucosa, another from a small accessory spleen in the tail of pancreas and the third was probably due to contrast accumulation in the body of pancreas seen 'end-on'. A false positive diagnosis may also derive from contrast accumulation in a hyperplastic lymphnode, a penetrating gatroduodenal ulcer, a pancreatic haemangioma or metastasis. Diagnostic specificity was 0.85, sensitivity 0.43.", "contents": "Angiographic localization of beta cell tumours. Angiography was carried out on 28 patients by which a beta cell tumour was verified in 21. One case was excluded as no final diagnosis was established. Angiography correctly localized 14/17 adenomas (82%) and 3/4 carcinomas (75%), in total 17/21 tumours (81%). The adenomas were equally distributed throughout the pancreas. Three false negative diagnoses included an adenoma in the head of pancreas seen in retrospect, a hypovascular adenoma in the head of pancreas and an adenoma in the tail of pancreas which probably was hidden by the spleen. All carcinomas were located in the body and tail of pancreas. Metastases to the liver were demonstrated in two cases, although present in all. One carcinoma was not distinguished from superimposed metastases in the left lobe of the liver. A false positive diagnosis was reported in 3/7 cases (57%). One resulted from accumulation of contrast in the duodenal mucosa, another from a small accessory spleen in the tail of pancreas and the third was probably due to contrast accumulation in the body of pancreas seen 'end-on'. A false positive diagnosis may also derive from contrast accumulation in a hyperplastic lymphnode, a penetrating gatroduodenal ulcer, a pancreatic haemangioma or metastasis. Diagnostic specificity was 0.85, sensitivity 0.43."}
{"id": "PMID:225783", "title": "Classification of pancreatic endocrine tumours.", "content": "Conventional or electron microscopy can contribute significantly to the diagnosis of pancreatic endocrine tumours. These techniques, however, are of limited value for the classification of the tumours, which should take both clinical and morphological findings into account. In this paper a classification based on both the clinical features and on the content of peptide hormone-producing cells in the tumours is presented.", "contents": "Classification of pancreatic endocrine tumours. Conventional or electron microscopy can contribute significantly to the diagnosis of pancreatic endocrine tumours. These techniques, however, are of limited value for the classification of the tumours, which should take both clinical and morphological findings into account. In this paper a classification based on both the clinical features and on the content of peptide hormone-producing cells in the tumours is presented."}
{"id": "PMID:225784", "title": "Radioimmunoassay in diagnosis, localization and treatment of endocrine tumours in gut and pancreas.", "content": "Pancreas and gut hormones are involved in many endocrine and gastrointestinal diseases. Radioimmunoassays for these hormones have proved particularly valuable in diagnosis, localisation and control of treatment of endocrine tumours, of which many are mixed. An estimate based on ten years experience in a homogenous population of 5 million inhabitants (Denmark) suggests, that endocrine gut tumour-syndromes on an average appear with an incidence of 1 patient per year/syndrome/million. At present six different syndromes are known: 1) The insulinoma syndrome, 2) The Zollinger-Ellison syndrome.3) The Verner-Morrison syndrome. 4) The glucagonoma syndrome. 5) The somatostatinoma syndrome, and 6) the carcinoid syndrome. Accordingly diagnostically valuable RIAs for pancreas and gut hormones include those for insulin, gastrin, VIP, HPP, glucagon, somatostatin, and presumably also substance P. It is probably safe to predict that the need for gut and pancreas hormone RIAs within the next decade will increase greatly in order to assure proper management of tumours producing gastroentero-pancreatic hormones.", "contents": "Radioimmunoassay in diagnosis, localization and treatment of endocrine tumours in gut and pancreas. Pancreas and gut hormones are involved in many endocrine and gastrointestinal diseases. Radioimmunoassays for these hormones have proved particularly valuable in diagnosis, localisation and control of treatment of endocrine tumours, of which many are mixed. An estimate based on ten years experience in a homogenous population of 5 million inhabitants (Denmark) suggests, that endocrine gut tumour-syndromes on an average appear with an incidence of 1 patient per year/syndrome/million. At present six different syndromes are known: 1) The insulinoma syndrome, 2) The Zollinger-Ellison syndrome.3) The Verner-Morrison syndrome. 4) The glucagonoma syndrome. 5) The somatostatinoma syndrome, and 6) the carcinoid syndrome. Accordingly diagnostically valuable RIAs for pancreas and gut hormones include those for insulin, gastrin, VIP, HPP, glucagon, somatostatin, and presumably also substance P. It is probably safe to predict that the need for gut and pancreas hormone RIAs within the next decade will increase greatly in order to assure proper management of tumours producing gastroentero-pancreatic hormones."}
{"id": "PMID:225785", "title": "The clinical diagnosis of insulinoma.", "content": "Based on the literature and on experience and on experience with 23 cases the clinical diagnosis of insulinomas is reviewed. In clinical praxis the diagnostic steps can usually be simplified to a demonstration of fasting, symptomatic hypoglycaemia. Hence, we have used the 72-hour fast as the single diagnostic test for insulinomas during the last 5 years. Pro-insulin measurements may be a valuable supplementary tool. Other diagnostic tests are probably of little importance.", "contents": "The clinical diagnosis of insulinoma. Based on the literature and on experience and on experience with 23 cases the clinical diagnosis of insulinomas is reviewed. In clinical praxis the diagnostic steps can usually be simplified to a demonstration of fasting, symptomatic hypoglycaemia. Hence, we have used the 72-hour fast as the single diagnostic test for insulinomas during the last 5 years. Pro-insulin measurements may be a valuable supplementary tool. Other diagnostic tests are probably of little importance."}
{"id": "PMID:225786", "title": "Delay in the diagnosis of insulinomas.", "content": "The median diagnostic delay in 32 patients with verified insulinomas was 2 3/4 years (range 1/4--18). The median delay in the 1939--1958 period was shorter (2 years, n = 17) than in the 1959--1978 period (3 years, n = 15). Thus, modern developments with insulin estimations were without noticeable effect upon the diagnostic delay. The findings can probably only be explained by a poor awareness of the insulinoma syndrome in the medical profession.", "contents": "Delay in the diagnosis of insulinomas. The median diagnostic delay in 32 patients with verified insulinomas was 2 3/4 years (range 1/4--18). The median delay in the 1939--1958 period was shorter (2 years, n = 17) than in the 1959--1978 period (3 years, n = 15). Thus, modern developments with insulin estimations were without noticeable effect upon the diagnostic delay. The findings can probably only be explained by a poor awareness of the insulinoma syndrome in the medical profession."}
{"id": "PMID:225787", "title": "Strategy in the diagnosis of insulinoma.", "content": "A simple diagnostic strategy in the diagnosis of insulinoma in adult subjects is proposed based upon the literature and own experiences. It comprises measurement of plasma proinsulin, insulin and C-peptide as well as blood glucose after an overnight fast. When a low or normal proinsulin concentration is found, organic hyperinsulinaemia is very unlikely, while elevated proinsulin, after exclusion of uremia, hepatic cirrhosis, thyreotoxicosis and surreptitious administration of insulin or sulfonylurea drugs, strongly indicates this condition.", "contents": "Strategy in the diagnosis of insulinoma. A simple diagnostic strategy in the diagnosis of insulinoma in adult subjects is proposed based upon the literature and own experiences. It comprises measurement of plasma proinsulin, insulin and C-peptide as well as blood glucose after an overnight fast. When a low or normal proinsulin concentration is found, organic hyperinsulinaemia is very unlikely, while elevated proinsulin, after exclusion of uremia, hepatic cirrhosis, thyreotoxicosis and surreptitious administration of insulin or sulfonylurea drugs, strongly indicates this condition."}
{"id": "PMID:225788", "title": "Elevated serum proinsulin in beta cell nesidioblastosis. Report of a case in a newborn.", "content": "A newborn infant with severe hypoglycaemia and nesidioblastosis was subjected to subtotal pancreatectomy without any sign of improvement. In spite of very low plasma levels of glucose (i.e. less than 1 mmol/l) plasma insulin concentrations were high (i.e. greater than 700 pmol/l). Plasma proinsulin was considerably enhanced comprising 43% of the total insulin immunoreactivity. Plasma glucagon concentrations were normal. Postoperatively normal to subnormal plasma glucose levels could only be maintained by treatment with frequent meals, diazoxide and intramuscular injections of a long-acting glucagon preparation. With time, signs of mental retardation became obvious.", "contents": "Elevated serum proinsulin in beta cell nesidioblastosis. Report of a case in a newborn. A newborn infant with severe hypoglycaemia and nesidioblastosis was subjected to subtotal pancreatectomy without any sign of improvement. In spite of very low plasma levels of glucose (i.e. less than 1 mmol/l) plasma insulin concentrations were high (i.e. greater than 700 pmol/l). Plasma proinsulin was considerably enhanced comprising 43% of the total insulin immunoreactivity. Plasma glucagon concentrations were normal. Postoperatively normal to subnormal plasma glucose levels could only be maintained by treatment with frequent meals, diazoxide and intramuscular injections of a long-acting glucagon preparation. With time, signs of mental retardation became obvious."}
{"id": "PMID:225789", "title": "Possible entries to the diagnosis of a glucagon-producing tumour.", "content": "Most, if not all, of the glucagon-producing tumours of the pancreas are malignant. For this reason an early diagnosis is essential. The glucagonoma syndrome is associated with a skin rash, stomatitis, anaemia, glucose-intolerance, hypoaminoacidaemia, weight loss, elevated sedimentation rate and hyperglucagonaemia. The more important and constant findings are the skin lesion, the low level of aminoacids in the blood and the increased glucagon concentrations. The skin lesion is not pathognomonic, but any therapy-resistant bullous dermatosis which microscopically is characterized by epidermal changes should alert the clinician to suspect a glucagonoma. The syndrome can be proved by demonstration of hyperglucagonaemia and a pancreatic tumour.", "contents": "Possible entries to the diagnosis of a glucagon-producing tumour. Most, if not all, of the glucagon-producing tumours of the pancreas are malignant. For this reason an early diagnosis is essential. The glucagonoma syndrome is associated with a skin rash, stomatitis, anaemia, glucose-intolerance, hypoaminoacidaemia, weight loss, elevated sedimentation rate and hyperglucagonaemia. The more important and constant findings are the skin lesion, the low level of aminoacids in the blood and the increased glucagon concentrations. The skin lesion is not pathognomonic, but any therapy-resistant bullous dermatosis which microscopically is characterized by epidermal changes should alert the clinician to suspect a glucagonoma. The syndrome can be proved by demonstration of hyperglucagonaemia and a pancreatic tumour."}
{"id": "PMID:225790", "title": "Verner-Morrison syndrome and vasoactive intestinal polypeptide (VIP).", "content": "The clinical features of the Verner-Morrison syndrome are surveyed. This rare clinical entity still needs to be more clearly defined. Especially in relation to the role of VIP and the clinical value of VIP measurements. A case with a good correlation between the activity of the disease and circulating VIP is presented.", "contents": "Verner-Morrison syndrome and vasoactive intestinal polypeptide (VIP). The clinical features of the Verner-Morrison syndrome are surveyed. This rare clinical entity still needs to be more clearly defined. Especially in relation to the role of VIP and the clinical value of VIP measurements. A case with a good correlation between the activity of the disease and circulating VIP is presented."}
{"id": "PMID:225792", "title": "Majority and minority cell populations in GEP and bronchial endocrine tumours.", "content": "Gastro-entero-pancreatic (GEP) and bronchial endocrine tumours have been studied by immunohistochemistry using specific antisera against a variety of hormonal and neuronal peptides. In gastrinomas numerous tumour cells were found to contain GH-like immunoreactivity. These cells were identical with those storing gastrin. Gastrinomas as a rule were extremely heterogeneous containing a variety of minority cell populations, including CCK immunoreactive cells and neurotensin immunoreactive cells. Glucagonoma cells were found to store GIP-like material in addition to glucagon. In some insulinomas calcitonin-like material was encountered in the insulin producing tumour cells. In both glucagonomas and insulinomas other pancreatic endocrine cell types constituted minority cell populations. One intestinal somatostatinoma contained gastrin cells as a minority cell population. Bronchial endocrine tumours contained scattered cells displaying ACTH-like or enkephalin-like immunoreactivity. Two such tumours in addition contained cells displaying neurophysin immunoreactivity.", "contents": "Majority and minority cell populations in GEP and bronchial endocrine tumours. Gastro-entero-pancreatic (GEP) and bronchial endocrine tumours have been studied by immunohistochemistry using specific antisera against a variety of hormonal and neuronal peptides. In gastrinomas numerous tumour cells were found to contain GH-like immunoreactivity. These cells were identical with those storing gastrin. Gastrinomas as a rule were extremely heterogeneous containing a variety of minority cell populations, including CCK immunoreactive cells and neurotensin immunoreactive cells. Glucagonoma cells were found to store GIP-like material in addition to glucagon. In some insulinomas calcitonin-like material was encountered in the insulin producing tumour cells. In both glucagonomas and insulinomas other pancreatic endocrine cell types constituted minority cell populations. One intestinal somatostatinoma contained gastrin cells as a minority cell population. Bronchial endocrine tumours contained scattered cells displaying ACTH-like or enkephalin-like immunoreactivity. Two such tumours in addition contained cells displaying neurophysin immunoreactivity."}
{"id": "PMID:225793", "title": "Pancreatic-polypeptide (PP) and endocrine tumours of the pancreas.", "content": "The role of human pancreatic-polypeptide in endocrine tumours of the pancreas is reviewed. Pancreatic-polypeptide may be involved in 3 different ways: 1. In cases with pure PP producing tumours. 2. In mixed endocrine tumours containing PP cells. 3. In cases with PP cell hyperplasia in normal pancreatic tissue associated with endocrine pancreatic tumours as VIP-omas, insulinomas, and glucagonomas. PP does not seem to serve as a general marker for endocrine tumours of the pancreas, but PP determinations are useful in patients wbith watery diarrhoea syndromes, because such syndromes may be associated with tumours that contain PP cells. Large molecular forms of PP occur in plasma from patients with endocrine tumours and high PP concentrations, but may also be found in other groups of patients. It is suggested that an atropin-suppression test could be of diagnostic value in revealing patients with increased serum concentrations of PP from other causes than vagal stimulation of normal PP cells.", "contents": "Pancreatic-polypeptide (PP) and endocrine tumours of the pancreas. The role of human pancreatic-polypeptide in endocrine tumours of the pancreas is reviewed. Pancreatic-polypeptide may be involved in 3 different ways: 1. In cases with pure PP producing tumours. 2. In mixed endocrine tumours containing PP cells. 3. In cases with PP cell hyperplasia in normal pancreatic tissue associated with endocrine pancreatic tumours as VIP-omas, insulinomas, and glucagonomas. PP does not seem to serve as a general marker for endocrine tumours of the pancreas, but PP determinations are useful in patients wbith watery diarrhoea syndromes, because such syndromes may be associated with tumours that contain PP cells. Large molecular forms of PP occur in plasma from patients with endocrine tumours and high PP concentrations, but may also be found in other groups of patients. It is suggested that an atropin-suppression test could be of diagnostic value in revealing patients with increased serum concentrations of PP from other causes than vagal stimulation of normal PP cells."}
{"id": "PMID:225797", "title": "Role of peripheral afferent nerve fiber in acupuncture analgesia elicited by needling point zusanli.", "content": "Needling acupuncture point zusanli shows a significant suppressive effect characterized by the response of jaw movement. The afferent analgesic impulses arising from the point zusanli for producing this effect are transmitted largely by A beta gamma fibers in the peroneal nerve. Sufficient amount of A beta gamma fibers brought in to action is an important factor in achieving this prominent analgesic effect. The inhibitory action of the large fibers, such as A beta gamma, mediating analgesic impulses upon the small fibers such as A delta and C, carrying painful impulses, seems to be one of the component parts of the mechanism of acupuncture analgesia.", "contents": "Role of peripheral afferent nerve fiber in acupuncture analgesia elicited by needling point zusanli. Needling acupuncture point zusanli shows a significant suppressive effect characterized by the response of jaw movement. The afferent analgesic impulses arising from the point zusanli for producing this effect are transmitted largely by A beta gamma fibers in the peroneal nerve. Sufficient amount of A beta gamma fibers brought in to action is an important factor in achieving this prominent analgesic effect. The inhibitory action of the large fibers, such as A beta gamma, mediating analgesic impulses upon the small fibers such as A delta and C, carrying painful impulses, seems to be one of the component parts of the mechanism of acupuncture analgesia."}
{"id": "PMID:225798", "title": "Calmodulin activation of adenylate cyclase in pancreatic islets.", "content": "Pancreatic islets contain calmodulin. The protein binds to a particulate fraction derived from the islets and stimulates adenylate cyclase activity in this subcellular fraction, both phenomena being activated by ionized calcium. A calcium-dependent stimulation of adenylate cyclase by endogenous calmodulin may contribute to the accumulation of adenosine 3',5'-monophosphate evoked by insulin releasing agents in the islet cells.", "contents": "Calmodulin activation of adenylate cyclase in pancreatic islets. Pancreatic islets contain calmodulin. The protein binds to a particulate fraction derived from the islets and stimulates adenylate cyclase activity in this subcellular fraction, both phenomena being activated by ionized calcium. A calcium-dependent stimulation of adenylate cyclase by endogenous calmodulin may contribute to the accumulation of adenosine 3',5'-monophosphate evoked by insulin releasing agents in the islet cells."}
{"id": "PMID:225799", "title": "[Destroyed lung (author's transl)].", "content": "The expression of \"destroyed lung\" is, now, accepted to designate the large destructions of the lung, secondary to pulmonary and essentially infectious diseases, the cure of which is obtained but with important sequelae. The main cause remains tuberculosis, cured by chemotherapy. Some large pulmonary suppurations, treated by antibiotics, can lead to the same sequelae. These \"destroyed lungs\" can keep an asymptomatic form. But often, about ten years after the initial disease, they cause several troubles such as progressive dyspnea leading to irreversible respiratory insufficiency, repeated pulmonary infectious episodes and hemoptysis, the risk of which is increased by aspergillosis. The radiological aspect of these \"destroyed lungs\" is made of opacities with multiple cavities or with one unique large cavity. The mechanism of hemoptysis has been understood recently: all destructive lesion of the pulmonary tissue produces as a consequence a development of the systemic blood circulation, bronchial or parietal, with reverse blood circulation from systemo-pulmonary anastomoses-which can produce capillary dilatations-into the pulmonary artery. All these complications can lead to a surgical treatment. Embolization of bronchial arteries is a less aggressive method when hemoptysis is the main symptom. These acquires \"destroyed lungs\" can be compared to those caused by extensive pseudokystic bronchiectases. For both cases clinical aspects and therapeutic methods are similar, though the lesions are fixed and likely congenital in the last form.", "contents": "[Destroyed lung (author's transl)]. The expression of \"destroyed lung\" is, now, accepted to designate the large destructions of the lung, secondary to pulmonary and essentially infectious diseases, the cure of which is obtained but with important sequelae. The main cause remains tuberculosis, cured by chemotherapy. Some large pulmonary suppurations, treated by antibiotics, can lead to the same sequelae. These \"destroyed lungs\" can keep an asymptomatic form. But often, about ten years after the initial disease, they cause several troubles such as progressive dyspnea leading to irreversible respiratory insufficiency, repeated pulmonary infectious episodes and hemoptysis, the risk of which is increased by aspergillosis. The radiological aspect of these \"destroyed lungs\" is made of opacities with multiple cavities or with one unique large cavity. The mechanism of hemoptysis has been understood recently: all destructive lesion of the pulmonary tissue produces as a consequence a development of the systemic blood circulation, bronchial or parietal, with reverse blood circulation from systemo-pulmonary anastomoses-which can produce capillary dilatations-into the pulmonary artery. All these complications can lead to a surgical treatment. Embolization of bronchial arteries is a less aggressive method when hemoptysis is the main symptom. These acquires \"destroyed lungs\" can be compared to those caused by extensive pseudokystic bronchiectases. For both cases clinical aspects and therapeutic methods are similar, though the lesions are fixed and likely congenital in the last form."}
{"id": "PMID:225801", "title": "[Carcino\u00efd heart disease: clinical, light and electron microscopic study (author's transl)].", "content": "The authors report a clinical and pathological case of carcino\u00efd heart disease in a 70-years old man. The primary carcino\u00efd tumor was ileal with both hepatic and neighbouring lymph node metastases. The clinical history was dominated by a typical carcino\u00efd syndrom biologically confirmed and accompanied by a tricuspid insufficiency. An autopsy permitted to described with precision the topography and extent of the cardiac affection. The originality of this work is due to the ultrastructural study which has rarely been done. This study permitted us to make some clinical histopathological, histogenetic and pathogenetic comments.", "contents": "[Carcino\u00efd heart disease: clinical, light and electron microscopic study (author's transl)]. The authors report a clinical and pathological case of carcino\u00efd heart disease in a 70-years old man. The primary carcino\u00efd tumor was ileal with both hepatic and neighbouring lymph node metastases. The clinical history was dominated by a typical carcino\u00efd syndrom biologically confirmed and accompanied by a tricuspid insufficiency. An autopsy permitted to described with precision the topography and extent of the cardiac affection. The originality of this work is due to the ultrastructural study which has rarely been done. This study permitted us to make some clinical histopathological, histogenetic and pathogenetic comments."}
{"id": "PMID:225802", "title": "[Supra trochlear femoral erosions. Their relations with gonarthrosis and chondrocalcinosis (author's transl)].", "content": "Studying one hundred cases of simple gonarthrosis we found only one supra trochlear femoral erosion (STFE). Such a lesion was discovered in 14 cases among 150 chondrocalcinosis with arthrosic lesions. The cases involving STFE trend to a commun marked chondro-osteolytic evolution. The caracteristic patella sizes show clearly that STFE is not in relation with en anomaly of patella (patella alta...). The upper osteophyte of the patella presents only a minor importance in the formation of STFE. This STFE formation begins probably with a progressive chondro-osteolysis of patella and trochlea. Then, appears a progressive nipping between the upper point of patella and the supra trochlear femoral bone.", "contents": "[Supra trochlear femoral erosions. Their relations with gonarthrosis and chondrocalcinosis (author's transl)]. Studying one hundred cases of simple gonarthrosis we found only one supra trochlear femoral erosion (STFE). Such a lesion was discovered in 14 cases among 150 chondrocalcinosis with arthrosic lesions. The cases involving STFE trend to a commun marked chondro-osteolytic evolution. The caracteristic patella sizes show clearly that STFE is not in relation with en anomaly of patella (patella alta...). The upper osteophyte of the patella presents only a minor importance in the formation of STFE. This STFE formation begins probably with a progressive chondro-osteolysis of patella and trochlea. Then, appears a progressive nipping between the upper point of patella and the supra trochlear femoral bone."}
{"id": "PMID:225803", "title": "[Therapy of chronic autonomous pancreatitis. Results in 147 cases (author's transl)].", "content": "The authors summarize their own personal experience acquired in the Department of Pr. Mercadier, concerning chronic pancreatitis. They attempt to define the factors influencing the choice of surgical technic, whilst emphasizing the grave nature of this condition, the long term prognosis of which remains severe in 50 per cent of cases.", "contents": "[Therapy of chronic autonomous pancreatitis. Results in 147 cases (author's transl)]. The authors summarize their own personal experience acquired in the Department of Pr. Mercadier, concerning chronic pancreatitis. They attempt to define the factors influencing the choice of surgical technic, whilst emphasizing the grave nature of this condition, the long term prognosis of which remains severe in 50 per cent of cases."}
{"id": "PMID:225804", "title": "[Accidental ingestion of caustic in childhood (author's transl)].", "content": "Accidental ingestion of caustic in childhood is not frequent but severe. It result in oesophagal burns progressing to stricture formation. 18 children with severe oesophagal burns were admitted during the six past years in the Intensive Care Unit of \"H\u00f4pital des Enfants-Malades\" in Paris. The authors report mainly two cases. They recommend oesophagoscopy and they propose a protocol of treating applied since 1974 in France and foreing countries. The present problem consists mainly in a preventive program to avoid kind of accidents and their sequels in children and their families and finally in the community.", "contents": "[Accidental ingestion of caustic in childhood (author's transl)]. Accidental ingestion of caustic in childhood is not frequent but severe. It result in oesophagal burns progressing to stricture formation. 18 children with severe oesophagal burns were admitted during the six past years in the Intensive Care Unit of \"H\u00f4pital des Enfants-Malades\" in Paris. The authors report mainly two cases. They recommend oesophagoscopy and they propose a protocol of treating applied since 1974 in France and foreing countries. The present problem consists mainly in a preventive program to avoid kind of accidents and their sequels in children and their families and finally in the community."}
{"id": "PMID:225805", "title": "[Necrotising enterocolitis. Report of 3 cases (author's transl)].", "content": "A review of clinical, pathological findings in 3 cases of necrotising enterocolitis is presented, as well as considerations about pathogenesis. The authors stress the benefits of hyperbarie oxygen in the treatment of the disease.", "contents": "[Necrotising enterocolitis. Report of 3 cases (author's transl)]. A review of clinical, pathological findings in 3 cases of necrotising enterocolitis is presented, as well as considerations about pathogenesis. The authors stress the benefits of hyperbarie oxygen in the treatment of the disease."}
{"id": "PMID:225806", "title": "[Chronic constrictive pericarditis complicating an apparently stable rheumatoid arthritis. Report of a new case (author's transl)].", "content": "The authors report a case of constrictive pericarditis complicating an apparently stable sero-negative rhumato\u00efd arthritis, a rarely described pathological association. The patient had a serious polyserositis due to an extremely marked and inflammatory pericardial constriction. The rhumato\u00efd origin was confirmed by pericardial effusion, histological and immunofluorescent studies. The inflammatory pericardial process rendered pericardiectomy virtually impossible and resulted in a fatal outcome.", "contents": "[Chronic constrictive pericarditis complicating an apparently stable rheumatoid arthritis. Report of a new case (author's transl)]. The authors report a case of constrictive pericarditis complicating an apparently stable sero-negative rhumato\u00efd arthritis, a rarely described pathological association. The patient had a serious polyserositis due to an extremely marked and inflammatory pericardial constriction. The rhumato\u00efd origin was confirmed by pericardial effusion, histological and immunofluorescent studies. The inflammatory pericardial process rendered pericardiectomy virtually impossible and resulted in a fatal outcome."}
{"id": "PMID:225807", "title": "[Duhring's and coeliac's diseases (author's transl)].", "content": "An atrophy of villi without digestive troubles is found in a 3 1/2 years old boy with a typical Duhring's disease. This observation proves the interest to research an enteropathy in case of dermatitis herpetiformis, and on the other hand the gluten free diet's efficacity on the cutaneous lesions. The authors consider cutaneous lesions's pathogeny and the antigenic relations between these two diseases.", "contents": "[Duhring's and coeliac's diseases (author's transl)]. An atrophy of villi without digestive troubles is found in a 3 1/2 years old boy with a typical Duhring's disease. This observation proves the interest to research an enteropathy in case of dermatitis herpetiformis, and on the other hand the gluten free diet's efficacity on the cutaneous lesions. The authors consider cutaneous lesions's pathogeny and the antigenic relations between these two diseases."}
{"id": "PMID:225808", "title": "[Some rare diseases of the esophagus (author's transl)].", "content": "Cancer excepted all other diseases of the esophagus are rare. Diverticula, benign tumors, perforations and the pathology of the cardia (hiatus hernia, achalasia and esophageal varices) are not studied here. We took into consideration the following diseases only: spasm of the cricopharyngeal muscle, Plummer-Vinson or Kelly-Paterson syndrome, cervical osteophytosis, dysphagia lusoria, benign and malignant mediastinal lymphatic nodes, Schatzki ring of the lower esophagus and esophageal duplications.", "contents": "[Some rare diseases of the esophagus (author's transl)]. Cancer excepted all other diseases of the esophagus are rare. Diverticula, benign tumors, perforations and the pathology of the cardia (hiatus hernia, achalasia and esophageal varices) are not studied here. We took into consideration the following diseases only: spasm of the cricopharyngeal muscle, Plummer-Vinson or Kelly-Paterson syndrome, cervical osteophytosis, dysphagia lusoria, benign and malignant mediastinal lymphatic nodes, Schatzki ring of the lower esophagus and esophageal duplications."}
{"id": "PMID:225809", "title": "[Histopathological findings in Hodgkin's disease (author's transl)].", "content": "The histological classification of Hodgkin's disease, as proposed by Lunkes and Butler, is incomplete and does not include all the morphological findings. The distinction between sub-varieties of the nodular sclerosing type and particular forms of the disease (interfollicular with necrosis, with xanthelasma, or epithelioid pseudo-metastatic cells) clearly demonstrates the large polymorphism of the ganglionic lesions. A study of the different types encountered in the same patient shows that there is probably a form which evolves from type 1 towards type 3 and then type 4, an another form characterized by nodular sclerosis. The distribution of the various varieties and sub-varieties were studied by the author in 442 ganglia and results were similar to those reported in other series: nodular sclerosing form: 38.2%; form without nodular sclerosis: 61.8% made up of H1: 10.6%, H3: 45.5%, H4: 5.6%.", "contents": "[Histopathological findings in Hodgkin's disease (author's transl)]. The histological classification of Hodgkin's disease, as proposed by Lunkes and Butler, is incomplete and does not include all the morphological findings. The distinction between sub-varieties of the nodular sclerosing type and particular forms of the disease (interfollicular with necrosis, with xanthelasma, or epithelioid pseudo-metastatic cells) clearly demonstrates the large polymorphism of the ganglionic lesions. A study of the different types encountered in the same patient shows that there is probably a form which evolves from type 1 towards type 3 and then type 4, an another form characterized by nodular sclerosis. The distribution of the various varieties and sub-varieties were studied by the author in 442 ganglia and results were similar to those reported in other series: nodular sclerosing form: 38.2%; form without nodular sclerosis: 61.8% made up of H1: 10.6%, H3: 45.5%, H4: 5.6%."}
{"id": "PMID:225811", "title": "[Retro-peritoneal tumors. Report of 21 cases (author's transl)].", "content": "The authors report their experience about 21 cases of retroperitoneal tumors. They emphasise their often late revelation, the frequent malignity and the involvement of the surroundings organs. They insist on the interest of the opacification of urinary tract and angiography and the value of echo-ranging and total body scanner to evaluate the characteristics of these tumors and theirs extensions. Recurrents are frequents and must be operated each time necessary.", "contents": "[Retro-peritoneal tumors. Report of 21 cases (author's transl)]. The authors report their experience about 21 cases of retroperitoneal tumors. They emphasise their often late revelation, the frequent malignity and the involvement of the surroundings organs. They insist on the interest of the opacification of urinary tract and angiography and the value of echo-ranging and total body scanner to evaluate the characteristics of these tumors and theirs extensions. Recurrents are frequents and must be operated each time necessary."}
{"id": "PMID:225810", "title": "[Delayed radionecrosis of the cerebral hemispheres following betatron electron beam irradiation for scalp cancer. Pathological and clinical findings in one case (author's transl)].", "content": "Three years following an irradiation by the Betatron's electron beam of an epithelioma in left parieto occipital area of the scalp in a female patient aged 77, early suffering from high blood pressure, a fatal pseudo-tumoral brain necrosis occurs presenting as a rapidly increasing from of Wernicke's aphasia. The necropsy shows intense radionecrosis lesions of the brain and the bone, free of any parenchymatous malignant proliferation note-worthy for the striking density of microvascular changes as previously described in radiation therapy. The case observed some years ago, allows to definite again the limits doses of the extracranial irradiations now estimated at 1760 rets. That is the \"Nominal Standard Dose\" (NSD) measured by rets and taking into account the number of seances (N) and the duration of irradiation (T) which would be to take the place of \"the total dose\" (D) (rads). These dosimetric criteria themselves must be adjusted to the age and the vascular features of each patient.", "contents": "[Delayed radionecrosis of the cerebral hemispheres following betatron electron beam irradiation for scalp cancer. Pathological and clinical findings in one case (author's transl)]. Three years following an irradiation by the Betatron's electron beam of an epithelioma in left parieto occipital area of the scalp in a female patient aged 77, early suffering from high blood pressure, a fatal pseudo-tumoral brain necrosis occurs presenting as a rapidly increasing from of Wernicke's aphasia. The necropsy shows intense radionecrosis lesions of the brain and the bone, free of any parenchymatous malignant proliferation note-worthy for the striking density of microvascular changes as previously described in radiation therapy. The case observed some years ago, allows to definite again the limits doses of the extracranial irradiations now estimated at 1760 rets. That is the \"Nominal Standard Dose\" (NSD) measured by rets and taking into account the number of seances (N) and the duration of irradiation (T) which would be to take the place of \"the total dose\" (D) (rads). These dosimetric criteria themselves must be adjusted to the age and the vascular features of each patient."}
{"id": "PMID:225812", "title": "[Bourneville's tuberose sclerosis in children (author's transl)].", "content": "In 20 out of a series of 30 children with Bourneville's disease, the diagnosis was made from the association of epilepsy and multiple achromic spots, before the appearance of adenomas. A total of 27 of these 30 children had these spots, and their characteristics are reviewed, as well as the average age of onset and frequency of the other typical cutaneous signs noted in this group: sebaceous adenomas, Koenen's tumors, and leather-grained skin plaques. Severe epilepsy was a constant finding and was often resistant to treatment: West's syndrome (18 cases), and Lennox Gastaut's syndrome (16 cases). Severe mental deficiency was also an almost constant finding and was increased by behavioural disorders: 11 out of the 13 children aged more than 5 years. Other locations of the disease included more particularly the ocular (8 cases), skeletal (11 cases), and renal (1 case) regions. In 5 cases, the disease had been transmitted by a parent, but in 3 of these it had not been recognized.", "contents": "[Bourneville's tuberose sclerosis in children (author's transl)]. In 20 out of a series of 30 children with Bourneville's disease, the diagnosis was made from the association of epilepsy and multiple achromic spots, before the appearance of adenomas. A total of 27 of these 30 children had these spots, and their characteristics are reviewed, as well as the average age of onset and frequency of the other typical cutaneous signs noted in this group: sebaceous adenomas, Koenen's tumors, and leather-grained skin plaques. Severe epilepsy was a constant finding and was often resistant to treatment: West's syndrome (18 cases), and Lennox Gastaut's syndrome (16 cases). Severe mental deficiency was also an almost constant finding and was increased by behavioural disorders: 11 out of the 13 children aged more than 5 years. Other locations of the disease included more particularly the ocular (8 cases), skeletal (11 cases), and renal (1 case) regions. In 5 cases, the disease had been transmitted by a parent, but in 3 of these it had not been recognized."}
{"id": "PMID:225814", "title": "[Diagnostic problems in the disseminated intraparenchymatous form of cerebral cysticercosis. A report on two cases (author's transl)].", "content": "The authors report 2 cases of brain localisation of cysticercosis due to Cysticercus cellulosae. In both cases epilepsy was found but only later was its origin proved by the finding of caracteristic ellipsoidal calcifications of cysticerci on the roentgenogram. The authors also recall the various possible symptoms; insist on the fact that early positive diagnosis is difficult and that the mode of treatment by surgery is exceptional. Though cysticercosis is rare in France, it should be remembered when a diagnosis of epilepsy is made and no apparent cause is found: further research of etiology should thus be made in such cases.", "contents": "[Diagnostic problems in the disseminated intraparenchymatous form of cerebral cysticercosis. A report on two cases (author's transl)]. The authors report 2 cases of brain localisation of cysticercosis due to Cysticercus cellulosae. In both cases epilepsy was found but only later was its origin proved by the finding of caracteristic ellipsoidal calcifications of cysticerci on the roentgenogram. The authors also recall the various possible symptoms; insist on the fact that early positive diagnosis is difficult and that the mode of treatment by surgery is exceptional. Though cysticercosis is rare in France, it should be remembered when a diagnosis of epilepsy is made and no apparent cause is found: further research of etiology should thus be made in such cases."}
{"id": "PMID:225815", "title": "[HLA in psoriasis, population and family studies (author's transl)].", "content": "We have detected B13 and BW17, respectively 6 and 20 times, in a dample of 51 psoriasis, versus, respectively 2 and 12 times in a sample of 140 control subjects. Two informative families have been investigated. In the first one, marker transmission and illness heredity were correlated, whereas, in the second one, both were dissociated. These observations allow to consider every physio-pathologic hypothesis linking HLA system and psoriasis vulgaris.", "contents": "[HLA in psoriasis, population and family studies (author's transl)]. We have detected B13 and BW17, respectively 6 and 20 times, in a dample of 51 psoriasis, versus, respectively 2 and 12 times in a sample of 140 control subjects. Two informative families have been investigated. In the first one, marker transmission and illness heredity were correlated, whereas, in the second one, both were dissociated. These observations allow to consider every physio-pathologic hypothesis linking HLA system and psoriasis vulgaris."}
{"id": "PMID:225816", "title": "[Pharmacological basis for a fixed association of hydrochlorothiazide, amiloride hydrochloride, and timolol maleate (author's transl)].", "content": "The treatment of hypertension requires in many cases a therapeutic combination. This survey, carried out in 96 cases, shows the interest of a fixed combination including a thiazide diuretic (hydrochlorothiazide), a potassium sparing (chlorhydrate of amiloride) and a beta-blocking agent (timolol maleate) as compared to therapy with a beta-blocking agent or diuretic alone. This combination, logical from a pharmacological view point, has proved significantly more effective (81% of patients were normalized) and as well tolerated (none additional side effect) as each of its components. As it simplifies prescription by reducing the number of tablets, it appears a considerable contribution to hypertension therapy.", "contents": "[Pharmacological basis for a fixed association of hydrochlorothiazide, amiloride hydrochloride, and timolol maleate (author's transl)]. The treatment of hypertension requires in many cases a therapeutic combination. This survey, carried out in 96 cases, shows the interest of a fixed combination including a thiazide diuretic (hydrochlorothiazide), a potassium sparing (chlorhydrate of amiloride) and a beta-blocking agent (timolol maleate) as compared to therapy with a beta-blocking agent or diuretic alone. This combination, logical from a pharmacological view point, has proved significantly more effective (81% of patients were normalized) and as well tolerated (none additional side effect) as each of its components. As it simplifies prescription by reducing the number of tablets, it appears a considerable contribution to hypertension therapy."}
{"id": "PMID:225817", "title": "[Bone in hepatic cirrhosis: morphometric and biological study (author's transl)].", "content": "Quantitative bone histomorphometry and evaluation of blood parameters have been performed in 24 patients with hepatic cirrhosis. 13 patients show osteoporosis which, in 8 of them, is associated with osteoclastic hyperactivity but without elevation of blood parathormon. All patients have hypocalcemia and 14 of them hyperosteidosis. These results are compared with data of the literature on bone morphometry and phosphocalcic metabolism during hepatic cirrhosis.", "contents": "[Bone in hepatic cirrhosis: morphometric and biological study (author's transl)]. Quantitative bone histomorphometry and evaluation of blood parameters have been performed in 24 patients with hepatic cirrhosis. 13 patients show osteoporosis which, in 8 of them, is associated with osteoclastic hyperactivity but without elevation of blood parathormon. All patients have hypocalcemia and 14 of them hyperosteidosis. These results are compared with data of the literature on bone morphometry and phosphocalcic metabolism during hepatic cirrhosis."}
{"id": "PMID:225813", "title": "[Hormonal status and hyperthyroidies (author's transl)].", "content": "The authors have compared \"clinic\" and \"biology\" in order to determine principal tests in vitro in: hyperthyro\u00efdie diagnostic: T3-FT4 rT3; hyperthyro\u00efdie form: TBG; treated greave's disease: FT4-TBG.", "contents": "[Hormonal status and hyperthyroidies (author's transl)]. The authors have compared \"clinic\" and \"biology\" in order to determine principal tests in vitro in: hyperthyro\u00efdie diagnostic: T3-FT4 rT3; hyperthyro\u00efdie form: TBG; treated greave's disease: FT4-TBG."}
{"id": "PMID:225818", "title": "[Treatment of alcohol withdrawal symptoms: a clinical study (author's transl)].", "content": "A total of 24 patients (20 men and 4 women) were treated for varying degrees of alcoholism. Tiapride was administered orally as 300 to 600 mg/day to 22 patients, the other two cases receiving i.v. injections followed by oral doses. Tiapride was extremely well-tolerated and no side-effects were noted. Withdrawal symptoms were effectively reduced, and a significant action was noted against tremor. Tiapride was also effective against depression and anxiety, and hallucinations disappeared in two cases.", "contents": "[Treatment of alcohol withdrawal symptoms: a clinical study (author's transl)]. A total of 24 patients (20 men and 4 women) were treated for varying degrees of alcoholism. Tiapride was administered orally as 300 to 600 mg/day to 22 patients, the other two cases receiving i.v. injections followed by oral doses. Tiapride was extremely well-tolerated and no side-effects were noted. Withdrawal symptoms were effectively reduced, and a significant action was noted against tremor. Tiapride was also effective against depression and anxiety, and hallucinations disappeared in two cases."}
{"id": "PMID:225820", "title": "[Management of carcinoma of the kidney with metastasis (author's transl)].", "content": "The discovery of pulmonary metastasis is not a contraindication to operation. In the light of 21 personal cases and a review of the literature, the authors give their arguments in favour of surgery. No pronostic criterion is certain except for two facts: 1) the course is capricious; 2) spontaneous remissions do not occur. The results of surgery alone do not seem to be influenced by radiotherapy nor chemotherapy.", "contents": "[Management of carcinoma of the kidney with metastasis (author's transl)]. The discovery of pulmonary metastasis is not a contraindication to operation. In the light of 21 personal cases and a review of the literature, the authors give their arguments in favour of surgery. No pronostic criterion is certain except for two facts: 1) the course is capricious; 2) spontaneous remissions do not occur. The results of surgery alone do not seem to be influenced by radiotherapy nor chemotherapy."}
{"id": "PMID:225825", "title": "Studies on the mechanisms underlying horizontal-bipolar interaction in the carp retina.", "content": "Responses of on-center bipolar cells and horizontal cells were recorded simultaneously in the carp retina, and the effect of polarization of horizontal cells on the bipolar cells was studied. Hyperpolarization by extrinsic current of horizontal cells elicited in the bipolar cells a hyperpolarizing response which, unlike the electrical coupling betweeen adjacent horizontal cells, was accompanied by a change in membrane conductance. The bipolar cell responses elicited by polarization of external horizontal cells showed a negative reversal potential, while those elicited by polarization of intermediate horizontal cells showed a positive reversal potential. It was suggested that the external horizontal cells modify the cone-bipolar transmission which involves the conductance change of subsynaptic potassium and/or chloride channels, while the intermediate horizontal cells modify the rod-bipolar transmission which involves the conductance change of sodium channels.", "contents": "Studies on the mechanisms underlying horizontal-bipolar interaction in the carp retina. Responses of on-center bipolar cells and horizontal cells were recorded simultaneously in the carp retina, and the effect of polarization of horizontal cells on the bipolar cells was studied. Hyperpolarization by extrinsic current of horizontal cells elicited in the bipolar cells a hyperpolarizing response which, unlike the electrical coupling betweeen adjacent horizontal cells, was accompanied by a change in membrane conductance. The bipolar cell responses elicited by polarization of external horizontal cells showed a negative reversal potential, while those elicited by polarization of intermediate horizontal cells showed a positive reversal potential. It was suggested that the external horizontal cells modify the cone-bipolar transmission which involves the conductance change of subsynaptic potassium and/or chloride channels, while the intermediate horizontal cells modify the rod-bipolar transmission which involves the conductance change of sodium channels."}
{"id": "PMID:225819", "title": "[Eighteen cases of desmomas (author's transl)].", "content": "In 14 years the authors have recorded 18 cases of desmomas. Most of the cases were situated in the 3rd and 4th decade. They only found 8 times the usual localization in the abdominal musculature. In five of their observations they found and accidental or surgical traumatism. The histopathological data are given and the ultrastructural examination reveals the fibrillogenetic activity of the tumoral cells. Multiple recurrences were observed in two cases; they concerned lesions localized in the members. No metastatic evolution was to be found.", "contents": "[Eighteen cases of desmomas (author's transl)]. In 14 years the authors have recorded 18 cases of desmomas. Most of the cases were situated in the 3rd and 4th decade. They only found 8 times the usual localization in the abdominal musculature. In five of their observations they found and accidental or surgical traumatism. The histopathological data are given and the ultrastructural examination reveals the fibrillogenetic activity of the tumoral cells. Multiple recurrences were observed in two cases; they concerned lesions localized in the members. No metastatic evolution was to be found."}
{"id": "PMID:225823", "title": "[Bronchial tumor and paraneoplastic syndrome of antiduresis: a new case of Schwartz-Bartter's syndrome (author's transl)].", "content": "The autors reports about a new case of Schwartz-Bartter's syndrome. Its first clinical manifestations are primarily the neuro-psychiatric disorder and the arterial hypertension. These manifestations were attributed to an inappropriate secretion of antidiuretic hormon, in relation with a bronchial neoplasm (oat-cell carcinoma). The tumor was removed surgically; shortly after the operation the biological disorders disappeared completely. But they reappeared 5 months later, indicating recurrence (local and metastatic). This recurrence started to present clinical manifestation, 2 months later. After a brief historical approach, the authors suggested the aetiology, the diagnosis circumstances and the biological criteria of Schwartz-Bartter's syndrome. Then later, the precised the main principles of its management.", "contents": "[Bronchial tumor and paraneoplastic syndrome of antiduresis: a new case of Schwartz-Bartter's syndrome (author's transl)]. The autors reports about a new case of Schwartz-Bartter's syndrome. Its first clinical manifestations are primarily the neuro-psychiatric disorder and the arterial hypertension. These manifestations were attributed to an inappropriate secretion of antidiuretic hormon, in relation with a bronchial neoplasm (oat-cell carcinoma). The tumor was removed surgically; shortly after the operation the biological disorders disappeared completely. But they reappeared 5 months later, indicating recurrence (local and metastatic). This recurrence started to present clinical manifestation, 2 months later. After a brief historical approach, the authors suggested the aetiology, the diagnosis circumstances and the biological criteria of Schwartz-Bartter's syndrome. Then later, the precised the main principles of its management."}
{"id": "PMID:225830", "title": "Primary mucus-secreting adenocarcinoma of the renal pelvis.", "content": "Mucus-secreting adenocarcinoma of the renal pelvis is an extremely rare tumor. It arises from multipotential transitional epithelium which is capable of undergoing metaplastic transformation when subjected to chronic irritation from calculi, hydronephrosis, or pyelonephritis. Women are affected slightly more often than men. Tumor invasion implies a poor prognosis. Long-term survival occurs but is infrequent. In the case reported, preoperative angiography yielded useful diagnostic information.", "contents": "Primary mucus-secreting adenocarcinoma of the renal pelvis. Mucus-secreting adenocarcinoma of the renal pelvis is an extremely rare tumor. It arises from multipotential transitional epithelium which is capable of undergoing metaplastic transformation when subjected to chronic irritation from calculi, hydronephrosis, or pyelonephritis. Women are affected slightly more often than men. Tumor invasion implies a poor prognosis. Long-term survival occurs but is infrequent. In the case reported, preoperative angiography yielded useful diagnostic information."}
{"id": "PMID:225821", "title": "[Technical notes about radiculosaccography (author's transl)].", "content": "We insist about the following notions: contra-indications: epilepsy, papillary stasis, important ethylism, folliculitis in the lumbar punction area; preparation by intra-venous hydrocortisone and Primperan in two different syringes (to prevent lipothymia and vomiting); localisation by TV of the space L2-L3; cytology and albumin in the cerebrospinal fluid; localised X-rays on the suspected intervertebral disk.", "contents": "[Technical notes about radiculosaccography (author's transl)]. We insist about the following notions: contra-indications: epilepsy, papillary stasis, important ethylism, folliculitis in the lumbar punction area; preparation by intra-venous hydrocortisone and Primperan in two different syringes (to prevent lipothymia and vomiting); localisation by TV of the space L2-L3; cytology and albumin in the cerebrospinal fluid; localised X-rays on the suspected intervertebral disk."}
{"id": "PMID:225822", "title": "[Rupture of an aneurysm of the splenic artery into the pancreas, a rare cause of gastrointestinal bleeding (author's transl)].", "content": "In a 73 year old man, repeated gastrointestinal haemorrhages first attributed to peptic oesophagitis, recurred despite anti-reflux surgery. Upper endoscopy being negative, arteriography was performed which revealed the presence of a fissured aneurysm of the splenic artery. This was successfully treated by left splenopancreatectomy. A communication between the aneurysm and wirsung's duct was found in the operative specimen. This a very rare cause of gastrointestinal bleeding. The diagnosis can be made only by arteriography.", "contents": "[Rupture of an aneurysm of the splenic artery into the pancreas, a rare cause of gastrointestinal bleeding (author's transl)]. In a 73 year old man, repeated gastrointestinal haemorrhages first attributed to peptic oesophagitis, recurred despite anti-reflux surgery. Upper endoscopy being negative, arteriography was performed which revealed the presence of a fissured aneurysm of the splenic artery. This was successfully treated by left splenopancreatectomy. A communication between the aneurysm and wirsung's duct was found in the operative specimen. This a very rare cause of gastrointestinal bleeding. The diagnosis can be made only by arteriography."}
{"id": "PMID:225824", "title": "[Paralytic shellfish poisoning (author's transl)].", "content": "Different diseases as viral or bacterian gastro-enteritis, Tiphoid, viral hepatitis can come from shellfishes. Less known is the shellfish poisoning although recent outbreaks took place in Spain, France, England, Morocco. Toxic poisoning is caused by a poison produced by dinoflagelates of plankton which get developped in shells and make them dangerous, even cooked, to be eaten. A respiratory failure can result from this neurotropic poison.", "contents": "[Paralytic shellfish poisoning (author's transl)]. Different diseases as viral or bacterian gastro-enteritis, Tiphoid, viral hepatitis can come from shellfishes. Less known is the shellfish poisoning although recent outbreaks took place in Spain, France, England, Morocco. Toxic poisoning is caused by a poison produced by dinoflagelates of plankton which get developped in shells and make them dangerous, even cooked, to be eaten. A respiratory failure can result from this neurotropic poison."}
{"id": "PMID:225834", "title": "Endocrine function in sclerosteosis.", "content": "Sclerosteosis is a rare autosomal recessive condition which is characterized by excessive skeletal overgrowth, distortion of the facies, cranial nerve abnormalities and raised intracranial pressure. Syndactyly and digital malformation are associated features. Radiological examination reveals thickened sclerotic bone maximally involving the skull, including the pituitary fossa. Sclerosis and hyperostosis are present throughout the skeleton. Biochemical and endocrine tests were carred out on 3 patients with sclerosteosis in an attempt to detect any dysfunction of calcium regulation of the pituitary. Results revealed no abnormality of basal parathyroid or calcitonin secretion. Histological examination revealed quantitatively increased bone resorption in comparison with normal subjects, although the pattern resembled osteosclerosis. Regulation of growth hormone, adrenocorticotrophin, gonadotrophin and thyrotrophin function were intact. We conclude that pituitary function and calcium 'homeostasis' are normal in this disorder.", "contents": "Endocrine function in sclerosteosis. Sclerosteosis is a rare autosomal recessive condition which is characterized by excessive skeletal overgrowth, distortion of the facies, cranial nerve abnormalities and raised intracranial pressure. Syndactyly and digital malformation are associated features. Radiological examination reveals thickened sclerotic bone maximally involving the skull, including the pituitary fossa. Sclerosis and hyperostosis are present throughout the skeleton. Biochemical and endocrine tests were carred out on 3 patients with sclerosteosis in an attempt to detect any dysfunction of calcium regulation of the pituitary. Results revealed no abnormality of basal parathyroid or calcitonin secretion. Histological examination revealed quantitatively increased bone resorption in comparison with normal subjects, although the pattern resembled osteosclerosis. Regulation of growth hormone, adrenocorticotrophin, gonadotrophin and thyrotrophin function were intact. We conclude that pituitary function and calcium 'homeostasis' are normal in this disorder."}
{"id": "PMID:225835", "title": "The role of physical activity in the prevention of ischaemic heart disease. A review.", "content": "It has been demonstrated that vigorous leisure-time physical activity and hard physical occupational work protect against ischaemic heart disease (IHD), but the protective mechanisms are not clear. According to most research reports programmes of regular physical activity do not lower serum cholesterol concentrations, but they do lower serum triglyceride levels. Dedicated marathon runners have lower serum low density lipoprotein and higher high density lipoprotein levels than controls, but it has not been proved that this lipoprotein pattern is the result of regular, high-intensity exercise. Regular physical exercise lowers the blood pressure to a greater degree in hypertensives than in controls. An exercise programme plus diet had no greater effect on serum total cholesterol levels than did diet alone on subjects with primary hyperlipoproteinaemia types IIa, IIb and IV. However, in types IIb and IV the exercise programme plus diet was more effective than diet alone in lowering serum triglyceride levels. The results of these studies are not valid for deciding whether regular exercise decreases the IHD risk factors studied. Such judgements must be based upon the results of randomized, controlled trials. The only satisfactory trial of this nature to date was done in Helsinki, and its results were inconclusive.", "contents": "The role of physical activity in the prevention of ischaemic heart disease. A review. It has been demonstrated that vigorous leisure-time physical activity and hard physical occupational work protect against ischaemic heart disease (IHD), but the protective mechanisms are not clear. According to most research reports programmes of regular physical activity do not lower serum cholesterol concentrations, but they do lower serum triglyceride levels. Dedicated marathon runners have lower serum low density lipoprotein and higher high density lipoprotein levels than controls, but it has not been proved that this lipoprotein pattern is the result of regular, high-intensity exercise. Regular physical exercise lowers the blood pressure to a greater degree in hypertensives than in controls. An exercise programme plus diet had no greater effect on serum total cholesterol levels than did diet alone on subjects with primary hyperlipoproteinaemia types IIa, IIb and IV. However, in types IIb and IV the exercise programme plus diet was more effective than diet alone in lowering serum triglyceride levels. The results of these studies are not valid for deciding whether regular exercise decreases the IHD risk factors studied. Such judgements must be based upon the results of randomized, controlled trials. The only satisfactory trial of this nature to date was done in Helsinki, and its results were inconclusive."}
{"id": "PMID:225836", "title": "Transfer of the herpes simplex thymidine kinase gene from human cells to mouse cells by means of metaphase chromosomes.", "content": "Thymidine kinase (TK)-deficient human cells were infected with ultraviolet light-inactivated Herpes simplex virus type 1, and \"transformed\" cells that expressed Herpes TK activity were isolated. Purified metaphase chromosomes were isolated from the transformed human line and incubated with TK-deficient mouse cells. TK+ cells were selected, and it was shown that these cells were gene transferents which expressed Herpes TK activity, identical to that found in the transformed human cells. The gene transferents contained no intact human chromosomes. When removed from selective pressure, the gene transferents rapidly lost the TK+ phenotype. However, upon continued growth in nonselective medium, a subpopulation in which the TK+ phenotype had become more stabilized appeared. These results suggest that the Herpes gene for thymidine kinase has integrated into the genome of the HSV-transformed human cells and that it can be transferred to other cells by means of purified metaphase chromosomes.", "contents": "Transfer of the herpes simplex thymidine kinase gene from human cells to mouse cells by means of metaphase chromosomes. Thymidine kinase (TK)-deficient human cells were infected with ultraviolet light-inactivated Herpes simplex virus type 1, and \"transformed\" cells that expressed Herpes TK activity were isolated. Purified metaphase chromosomes were isolated from the transformed human line and incubated with TK-deficient mouse cells. TK+ cells were selected, and it was shown that these cells were gene transferents which expressed Herpes TK activity, identical to that found in the transformed human cells. The gene transferents contained no intact human chromosomes. When removed from selective pressure, the gene transferents rapidly lost the TK+ phenotype. However, upon continued growth in nonselective medium, a subpopulation in which the TK+ phenotype had become more stabilized appeared. These results suggest that the Herpes gene for thymidine kinase has integrated into the genome of the HSV-transformed human cells and that it can be transferred to other cells by means of purified metaphase chromosomes."}
{"id": "PMID:225837", "title": "Glucagon stimulated plasma cyclic adenosine-3',5'-monophosphate in the differential diagnosis of jaundice.", "content": "The amount of plasma cyclic adenosine-3',5'-monophosphate was estimated before and 15 minutes after the intravenous injection of 1 milligram of glucagon in 34 patients with obstructive and in 23 patients with nonobstructive jaundice. After stimulation with glucagon, the median adenosine-3',5'-monophosphate concentration in obstructive jaundice rose fortyfold or more, while in nonobstructive jaundice, the increase was twentyfold or less. The difference was highly significant. The results indicate that this test can be useful in the differential diagnosis of obstructive and nonobstructive jaundice.", "contents": "Glucagon stimulated plasma cyclic adenosine-3',5'-monophosphate in the differential diagnosis of jaundice. The amount of plasma cyclic adenosine-3',5'-monophosphate was estimated before and 15 minutes after the intravenous injection of 1 milligram of glucagon in 34 patients with obstructive and in 23 patients with nonobstructive jaundice. After stimulation with glucagon, the median adenosine-3',5'-monophosphate concentration in obstructive jaundice rose fortyfold or more, while in nonobstructive jaundice, the increase was twentyfold or less. The difference was highly significant. The results indicate that this test can be useful in the differential diagnosis of obstructive and nonobstructive jaundice."}
{"id": "PMID:225839", "title": "Lung cancer in Malaysia.", "content": "Between 1967 and 1976, 388 cases of lung cancer were seen at the University Hospital, Kuala Lumpur, with histological confirmation in 72%. Most were aged from 50--80, with a male to female ratio of 2.8 : 1. The patients were predominantly of Chinese origin (82%) and from the lower socioeconomic strata. A history of smoking was elicited in 78%. The chief clinical and radiological features and the diagnostic methods are presented. The incidence of the histological types was squamous carcinoma 34%, adenocarcinoma 25%, large cell carcinoma 12%, small (oat) cell carcinoma 12%, \"unidifferentiated/anaplastic\" 15%, and others 2%. Malays appeared to have a higher percentage of adenocarcinoma. A comparison between the histologically confirmed group and the rest showed no significant difference in features. Problems pertaining to the management of Malaysian patients are discussed.", "contents": "Lung cancer in Malaysia. Between 1967 and 1976, 388 cases of lung cancer were seen at the University Hospital, Kuala Lumpur, with histological confirmation in 72%. Most were aged from 50--80, with a male to female ratio of 2.8 : 1. The patients were predominantly of Chinese origin (82%) and from the lower socioeconomic strata. A history of smoking was elicited in 78%. The chief clinical and radiological features and the diagnostic methods are presented. The incidence of the histological types was squamous carcinoma 34%, adenocarcinoma 25%, large cell carcinoma 12%, small (oat) cell carcinoma 12%, \"unidifferentiated/anaplastic\" 15%, and others 2%. Malays appeared to have a higher percentage of adenocarcinoma. A comparison between the histologically confirmed group and the rest showed no significant difference in features. Problems pertaining to the management of Malaysian patients are discussed."}
{"id": "PMID:225840", "title": "Diagnostic accuracy of cytology and biopsy in primary bronchial carcinoma.", "content": "The accuracy of diagnosis of cell type obtained from sputum cytology, bronchial aspirate, bronchial biopsy, or percutaneous lung biopsy in 161 cases of confirmed primary lung cancer has been examined and the pretreatment histological diagnosis has been compared with the final diagnosis made after surgical resection or necropsy. The yield of positive diagnoses of malignancy obtained by each method of investigation in each cell type showed that cytological examination of sputum was the most accurate method, but a high degree of accuracy was also obtained by bronchoscopic aspiration and bronchial biopsy. Percutaneous lung biopsy was the most effective, but the least accurate, means of obtaining carcinoma cells. The level of diagnostic accuracy was highest in patients with squamous cell carcinoma. Accurate pretreatment diagnosis of patients with adenocarcinoma was particularly difficult, and only 20% of these cases were correctly diagnosed by investigation. Of seven patients with adenocarcinoma and a positive diagnosis of malignancy made on percutaneous lung biopsy, none was correctly diagnosed. The causes of error in diagnosis of cell type of primary lung cancer are discussed.", "contents": "Diagnostic accuracy of cytology and biopsy in primary bronchial carcinoma. The accuracy of diagnosis of cell type obtained from sputum cytology, bronchial aspirate, bronchial biopsy, or percutaneous lung biopsy in 161 cases of confirmed primary lung cancer has been examined and the pretreatment histological diagnosis has been compared with the final diagnosis made after surgical resection or necropsy. The yield of positive diagnoses of malignancy obtained by each method of investigation in each cell type showed that cytological examination of sputum was the most accurate method, but a high degree of accuracy was also obtained by bronchoscopic aspiration and bronchial biopsy. Percutaneous lung biopsy was the most effective, but the least accurate, means of obtaining carcinoma cells. The level of diagnostic accuracy was highest in patients with squamous cell carcinoma. Accurate pretreatment diagnosis of patients with adenocarcinoma was particularly difficult, and only 20% of these cases were correctly diagnosed by investigation. Of seven patients with adenocarcinoma and a positive diagnosis of malignancy made on percutaneous lung biopsy, none was correctly diagnosed. The causes of error in diagnosis of cell type of primary lung cancer are discussed."}
{"id": "PMID:225841", "title": "Peak flow rate records in the diagnosis of occupational asthma due to isocyanates.", "content": "Peak expiratory flow rate (PEFR) has been recorded hourly or two-hourly from waking to sleeping in workers with respiratory symptoms who were exposed to isocyanate fumes at work. Twenty-three recordings averaging 33 days duration were recorded in 20 workers. Each worker was also admitted for bronchial provocation testing to toluene di-isocyanate (TDI) or diphenylmethane di-isocyanate (MDI) fumes or both. A final assessment of work-related asthma made from subsequent work exposure was compared with the results of bronchial provocation testing and a subjective assessment of the peak flow records. Both techniques were specific and sensitive. Physiological patterns of occupational asthma were defined from the records of PEFR. The most striking finding was the slow recovery from work-induced asthma. This commonly took several days to start and in one worker took 70 days to complete after leaving work. Several workers developed a pattern resembling fixed airways obstruction after repeated exposure at work. The consequences of these findings for the recording of symptoms of occupational asthma are discussed and recommendations are made for the recording of PEFR in workers in general.", "contents": "Peak flow rate records in the diagnosis of occupational asthma due to isocyanates. Peak expiratory flow rate (PEFR) has been recorded hourly or two-hourly from waking to sleeping in workers with respiratory symptoms who were exposed to isocyanate fumes at work. Twenty-three recordings averaging 33 days duration were recorded in 20 workers. Each worker was also admitted for bronchial provocation testing to toluene di-isocyanate (TDI) or diphenylmethane di-isocyanate (MDI) fumes or both. A final assessment of work-related asthma made from subsequent work exposure was compared with the results of bronchial provocation testing and a subjective assessment of the peak flow records. Both techniques were specific and sensitive. Physiological patterns of occupational asthma were defined from the records of PEFR. The most striking finding was the slow recovery from work-induced asthma. This commonly took several days to start and in one worker took 70 days to complete after leaving work. Several workers developed a pattern resembling fixed airways obstruction after repeated exposure at work. The consequences of these findings for the recording of symptoms of occupational asthma are discussed and recommendations are made for the recording of PEFR in workers in general."}
{"id": "PMID:225842", "title": "Liquoid induced stasis and the generalized Shwartzman reaction. An electron microscopic study in blue foxes.", "content": "The composition of the occlusive material within dilated glomerular capillaries, following intravenous injections of Liquoid in blue foxes, was studied electron microscopically; it was found that it mainly consisted of a debris in which disintegrated red cells constituted the major component. Damaged platelets and necrotic endothelial remnants were other components. These observations were interpreted as a result of glomerular stasis, and it was concluded that stasis in glomerular capillaries is a basic event in the development of the renal lesions accompanying the generalized Shwartzman reaction.", "contents": "Liquoid induced stasis and the generalized Shwartzman reaction. An electron microscopic study in blue foxes. The composition of the occlusive material within dilated glomerular capillaries, following intravenous injections of Liquoid in blue foxes, was studied electron microscopically; it was found that it mainly consisted of a debris in which disintegrated red cells constituted the major component. Damaged platelets and necrotic endothelial remnants were other components. These observations were interpreted as a result of glomerular stasis, and it was concluded that stasis in glomerular capillaries is a basic event in the development of the renal lesions accompanying the generalized Shwartzman reaction."}
{"id": "PMID:225845", "title": "Cytotoxic effect of neocarzinostatin on human lymphoid cells.", "content": "Effect of a protein antitumor antibiotic, neocarzinostatin (NCS) was examined on Epstein-Barr virus (EBV)-carrying human lymphoid cell lines and normal human lymphocytes. A marked cytotoxic effect of NCS on umbilical cord lymphocytes freshly transformed by EBV was observed, whereas the cells before transformation were affected only very little by NCS. Majority of long-term cultured cell lines were affected only slightly, while shorter-term cultured lines were more susceptible to the effect of NCS. An uptake of FITC-labeled NCS into cells was examined by fluorescence microscopy. The incorporation by the freshly transformed cells was higher than that by the longer-term cultured cell lines. Normal lymphyocytes or heat-killed cells, however, incorporated FITC-NCS very little. On the basis of the known mode of action of NCS on DNA and the present observation, the cytotoxicity of NCS appeared to be exerted within the cells.", "contents": "Cytotoxic effect of neocarzinostatin on human lymphoid cells. Effect of a protein antitumor antibiotic, neocarzinostatin (NCS) was examined on Epstein-Barr virus (EBV)-carrying human lymphoid cell lines and normal human lymphocytes. A marked cytotoxic effect of NCS on umbilical cord lymphocytes freshly transformed by EBV was observed, whereas the cells before transformation were affected only very little by NCS. Majority of long-term cultured cell lines were affected only slightly, while shorter-term cultured lines were more susceptible to the effect of NCS. An uptake of FITC-labeled NCS into cells was examined by fluorescence microscopy. The incorporation by the freshly transformed cells was higher than that by the longer-term cultured cell lines. Normal lymphyocytes or heat-killed cells, however, incorporated FITC-NCS very little. On the basis of the known mode of action of NCS on DNA and the present observation, the cytotoxicity of NCS appeared to be exerted within the cells."}
{"id": "PMID:225847", "title": "The pattern of liver diseases in Singapore. An autopsy study.", "content": "This study is based on an analysis of 1839 consecutive necropsies. Liver diseases are common in Singapore. Of particular importance are cholelithiasis, cirrhosis and primary carcinoma of the liver. Gallstones are mainly of the pigment variety and a significant proportion are present in the bile ducts. The multiracial composition of the population is reflected in a difference in the pattern of liver diseases among the different ethnic groups. Indians are found to have more alcoholic hepatitis and cirrhosis which are often of the micronodular type, while the Chinese have significantly more macronodular cirrhosis and hepatocellular carcinoma. Clonorchiasis and schistosomiasis are confined to the immigrant Chinese. The pattern of liver diseases is changing. Cholangitis and cholangitic abscesses as a result of cholelithiasis are becoming more common while amoebic abscesses and hepatic ascariasis are definitely on the decline. This is attributable to improved sanitary conditions.", "contents": "The pattern of liver diseases in Singapore. An autopsy study. This study is based on an analysis of 1839 consecutive necropsies. Liver diseases are common in Singapore. Of particular importance are cholelithiasis, cirrhosis and primary carcinoma of the liver. Gallstones are mainly of the pigment variety and a significant proportion are present in the bile ducts. The multiracial composition of the population is reflected in a difference in the pattern of liver diseases among the different ethnic groups. Indians are found to have more alcoholic hepatitis and cirrhosis which are often of the micronodular type, while the Chinese have significantly more macronodular cirrhosis and hepatocellular carcinoma. Clonorchiasis and schistosomiasis are confined to the immigrant Chinese. The pattern of liver diseases is changing. Cholangitis and cholangitic abscesses as a result of cholelithiasis are becoming more common while amoebic abscesses and hepatic ascariasis are definitely on the decline. This is attributable to improved sanitary conditions."}
{"id": "PMID:225848", "title": "Breast cancer in Surinam.", "content": "Two hundred forty two breast malignancies, all in women, including 238 carcinomas and four sarcomas, were screened in surgical pathologic materials from 1964-1976 in Surinam (population 385,000). The histologic types were similar to those generally seen. The mean age was 55.1 years and the range 24 to 89 years; 45.8% of cases came from the Creole population. The incidence in this period is calculated at 9.5/100,000.", "contents": "Breast cancer in Surinam. Two hundred forty two breast malignancies, all in women, including 238 carcinomas and four sarcomas, were screened in surgical pathologic materials from 1964-1976 in Surinam (population 385,000). The histologic types were similar to those generally seen. The mean age was 55.1 years and the range 24 to 89 years; 45.8% of cases came from the Creole population. The incidence in this period is calculated at 9.5/100,000."}
{"id": "PMID:225849", "title": "The natural occurrence of Trypanozoon in domestic chicken in the Ivory Coast.", "content": "From a natural infected chicken (Gallus gallus var. domesticus) in the Ivory Coast trypanosomes were isolated using Mastomys natalensis as recipient animal. Trypanosomes were diagnosed as belonging to the subgenus Trypanozoon from its morphology and its infectivity for rodents. The stabilated stock was able to infect a laboratory chicken. The stock proved to be human plasma subresistant and showed electrophoretic patterns of three enzymes (ALAT III, ME I, PEP III) so far only seen in pig and dog originated Trypanozoon stocks from the same region surveyed. The discovery for the first time of chicken harbouring Trypanozoon has to be considered in epizootiology and epidemiology of trypanosomiases.", "contents": "The natural occurrence of Trypanozoon in domestic chicken in the Ivory Coast. From a natural infected chicken (Gallus gallus var. domesticus) in the Ivory Coast trypanosomes were isolated using Mastomys natalensis as recipient animal. Trypanosomes were diagnosed as belonging to the subgenus Trypanozoon from its morphology and its infectivity for rodents. The stabilated stock was able to infect a laboratory chicken. The stock proved to be human plasma subresistant and showed electrophoretic patterns of three enzymes (ALAT III, ME I, PEP III) so far only seen in pig and dog originated Trypanozoon stocks from the same region surveyed. The discovery for the first time of chicken harbouring Trypanozoon has to be considered in epizootiology and epidemiology of trypanosomiases."}
{"id": "PMID:225850", "title": "[Microspectrophotometric study of the crystalline inclusions in different strains of Amoeba proteus].", "content": "Using microspectrometric technique, integral extinction and extinction spectra of crystalline inclusions of two amoeba strains, C and Ct, have been studied. The analysis of extinction spectrum form allowed to suggest that the crystals seen in both amoeba strains have identical chemical composition, whereas the morphological differences between cells in their transparency may be due to different mode of the crystal package. The relative amount of the crystals was measured in both amoeba strains on the basis of the integral extinction value. The distinct differences between the strains were detected in the integral extinction value and in the extinction spectra, which allowed us to use these parameters as genetic markers in the experiments on the nuclear transplantation in amoeba.", "contents": "[Microspectrophotometric study of the crystalline inclusions in different strains of Amoeba proteus]. Using microspectrometric technique, integral extinction and extinction spectra of crystalline inclusions of two amoeba strains, C and Ct, have been studied. The analysis of extinction spectrum form allowed to suggest that the crystals seen in both amoeba strains have identical chemical composition, whereas the morphological differences between cells in their transparency may be due to different mode of the crystal package. The relative amount of the crystals was measured in both amoeba strains on the basis of the integral extinction value. The distinct differences between the strains were detected in the integral extinction value and in the extinction spectra, which allowed us to use these parameters as genetic markers in the experiments on the nuclear transplantation in amoeba."}
{"id": "PMID:225853", "title": "Mucinous adenocarcinoma of prostate.", "content": "Primary mucinous adenocarcinoma of the prostate is rare. The presence of mucin in prostatic carcinoma is usually associated with decreased tumor aggressiveness and increased survival rates. When mucinous adenocarcinoma of the prostate is found, it is necessary to exclude extraprostatic primary sources particularly from the urinary bladder and the gastrointestinal tract.", "contents": "Mucinous adenocarcinoma of prostate. Primary mucinous adenocarcinoma of the prostate is rare. The presence of mucin in prostatic carcinoma is usually associated with decreased tumor aggressiveness and increased survival rates. When mucinous adenocarcinoma of the prostate is found, it is necessary to exclude extraprostatic primary sources particularly from the urinary bladder and the gastrointestinal tract."}
{"id": "PMID:225856", "title": "Border disease: persistant infection with the virus.", "content": "Two genetically related sheep that produced border disease-affected lambs from successive pregnancies were identified. These sheep, and some of their progeny, were found to be persistently infected with a virus antigenically related to bovine virus diarrhoea/mucosal disease virus. Only one of the sheep developed detectable serum antibody to the virus, and this animal only produced it 12 months after being detected as infected. The epidemiological significance of sheep persistently infected with border disease virus is discussed.", "contents": "Border disease: persistant infection with the virus. Two genetically related sheep that produced border disease-affected lambs from successive pregnancies were identified. These sheep, and some of their progeny, were found to be persistently infected with a virus antigenically related to bovine virus diarrhoea/mucosal disease virus. Only one of the sheep developed detectable serum antibody to the virus, and this animal only produced it 12 months after being detected as infected. The epidemiological significance of sheep persistently infected with border disease virus is discussed."}
{"id": "PMID:225875", "title": "[Immunological reactivity study of patients with uterine trophoblastic tumors].", "content": "By using DNCB delayed hypersensitivity test, the reaction of spontaneous rosette formation (RSRF) and the reaction of inhibition of leucocytes migration the authors examined 55 female patients with different forms of trophoblastic tumors of the uterus and 15 females following the removal of the mole without any signs of the disease concerned. Forty three patients showed a positive DNCB test, 93 of them were completely cured, a negative test was noted in 12 patients, only a 50% cure being observed. RSRF indicated the increased level of rosette-forming cells from 4,7--28% up to 10,3--73% in a successful treatment and its decrease down to 0--5% in the tumor progression, except 7 patients showing reduced RFC levels after the recovery. The reaction of leucocytes migration inhibition has revealed a considerable depression of leucocytes migration (MI--from 0.35 to 0.78) in 18 of 25 patients with manifestations of an acute tumor process (72%). In 7 cases no inhibition was noted, in 6--the treatment being insignificantly effective or time-consuming. In 21 (47.8%) of 27 patients without any signs of the affection there was no inhibitory effect. Leucocytes of healthy donors failed to respond to the tumor extract in either of 24 cases.", "contents": "[Immunological reactivity study of patients with uterine trophoblastic tumors]. By using DNCB delayed hypersensitivity test, the reaction of spontaneous rosette formation (RSRF) and the reaction of inhibition of leucocytes migration the authors examined 55 female patients with different forms of trophoblastic tumors of the uterus and 15 females following the removal of the mole without any signs of the disease concerned. Forty three patients showed a positive DNCB test, 93 of them were completely cured, a negative test was noted in 12 patients, only a 50% cure being observed. RSRF indicated the increased level of rosette-forming cells from 4,7--28% up to 10,3--73% in a successful treatment and its decrease down to 0--5% in the tumor progression, except 7 patients showing reduced RFC levels after the recovery. The reaction of leucocytes migration inhibition has revealed a considerable depression of leucocytes migration (MI--from 0.35 to 0.78) in 18 of 25 patients with manifestations of an acute tumor process (72%). In 7 cases no inhibition was noted, in 6--the treatment being insignificantly effective or time-consuming. In 21 (47.8%) of 27 patients without any signs of the affection there was no inhibitory effect. Leucocytes of healthy donors failed to respond to the tumor extract in either of 24 cases."}
{"id": "PMID:225876", "title": "[Pattern of lymphogenic metastasizing of soft tissue malignant tumors].", "content": "The examination performed indicated metastases in regional lymph nodes in 34 (7.5%) of 453 patients with soft tissue malignancies. The presence of metastases aggravates considerably the prognosis: a 5-year survival was 6.6%. Great risk of metastatic proliferation is especially characteristic of rhabdomyosarcoma, non-classifiable blastoma and synovial sarcoma. Primary tumors develop metastases more frequently than recurrent ones. The probability of lymphogenic spread of metastases is the higher the larger the tumor size in young individuals, and also with skin involvement. Tumor infiltration of bones does not result in an increased percentage of lymphogenic metastasization. The proximity of a tumor to regional lymph nodes is not inherent in a higher risk of their metastatic involvement.", "contents": "[Pattern of lymphogenic metastasizing of soft tissue malignant tumors]. The examination performed indicated metastases in regional lymph nodes in 34 (7.5%) of 453 patients with soft tissue malignancies. The presence of metastases aggravates considerably the prognosis: a 5-year survival was 6.6%. Great risk of metastatic proliferation is especially characteristic of rhabdomyosarcoma, non-classifiable blastoma and synovial sarcoma. Primary tumors develop metastases more frequently than recurrent ones. The probability of lymphogenic spread of metastases is the higher the larger the tumor size in young individuals, and also with skin involvement. Tumor infiltration of bones does not result in an increased percentage of lymphogenic metastasization. The proximity of a tumor to regional lymph nodes is not inherent in a higher risk of their metastatic involvement."}
{"id": "PMID:225877", "title": "[Prognosis in malignant tumors of soft tissues].", "content": "The author reports the data on 348 patients with malignant tumors of soft tissues, operated upon within the period of 1946--70 inclusively, children being excluded from this number. Various factors were studied from the prognostic viewpoint. The data obtained enabled estimating the morphological tumor structures, other conditions being equal, as a factor of great importance. None of the factors should be regarded separately. The accumulation of observations and systematization of prognostic criteria seems to be absolutely essential. Prognostication in malignant tumors of soft tissues may aid in selecting an adequate extent of surgical intervention, in avoiding too traumatic procedures, thus contributing to patients' rehabilitation.", "contents": "[Prognosis in malignant tumors of soft tissues]. The author reports the data on 348 patients with malignant tumors of soft tissues, operated upon within the period of 1946--70 inclusively, children being excluded from this number. Various factors were studied from the prognostic viewpoint. The data obtained enabled estimating the morphological tumor structures, other conditions being equal, as a factor of great importance. None of the factors should be regarded separately. The accumulation of observations and systematization of prognostic criteria seems to be absolutely essential. Prognostication in malignant tumors of soft tissues may aid in selecting an adequate extent of surgical intervention, in avoiding too traumatic procedures, thus contributing to patients' rehabilitation."}
{"id": "PMID:225878", "title": "[Diagnosis and treatment of neck chemodectoma].", "content": "The work is based on the analysis of clinical data of 10 patients with chemodectoma of the neck, 8 of them being subjected to surgery. The diagnosis in 8 operated patients was confirmed histologically, 2 non-operated patients had angiographic manifestations. It is emphasized that carotid angiography plays an important role in establishing the diagnosis and differential diagnosis of benign and malignant chemodectoma. There were noted no mortality and postoperative complications. The oncological aspects of surgery for chemodectoma are also discussed.", "contents": "[Diagnosis and treatment of neck chemodectoma]. The work is based on the analysis of clinical data of 10 patients with chemodectoma of the neck, 8 of them being subjected to surgery. The diagnosis in 8 operated patients was confirmed histologically, 2 non-operated patients had angiographic manifestations. It is emphasized that carotid angiography plays an important role in establishing the diagnosis and differential diagnosis of benign and malignant chemodectoma. There were noted no mortality and postoperative complications. The oncological aspects of surgery for chemodectoma are also discussed."}
{"id": "PMID:225879", "title": "[Effect of adrenaline and hydrocortisone on thiamine absorption in the intestine].", "content": "The effect of a single intramuscular injection of adrenalin and hydrocortisone (0.5 mg/kg and 10 mg/kg, respectively) on the thiamine absorption was studied in an isolated part of the intestine in male albino rats. The hormonal action on the Na-K-ATPase activity in the intestinal mucosa was also investigated. The intestinal thiamine absorption rate was shown to increase 10 min after adrenalin and 60 min after hydrocortisone injection. The Na-K-ATPase activity in the intestinal mucosa rose 10 min after the adrenalin injection and did not change after the administration of hydrocortisone.", "contents": "[Effect of adrenaline and hydrocortisone on thiamine absorption in the intestine]. The effect of a single intramuscular injection of adrenalin and hydrocortisone (0.5 mg/kg and 10 mg/kg, respectively) on the thiamine absorption was studied in an isolated part of the intestine in male albino rats. The hormonal action on the Na-K-ATPase activity in the intestinal mucosa was also investigated. The intestinal thiamine absorption rate was shown to increase 10 min after adrenalin and 60 min after hydrocortisone injection. The Na-K-ATPase activity in the intestinal mucosa rose 10 min after the adrenalin injection and did not change after the administration of hydrocortisone."}
{"id": "PMID:225880", "title": "[Cell proliferation induction in a monolayer chick embryo culture by the Sendai virus].", "content": "The response of cells on monolayer chick embryo cultures to infection with Sendai virus was studied. Total infection leads to the death of the cells within 3--5 days postinoculation which permits this system to be considered as lytic. Its significant difference from other systems with the lytic outcome of interaction of non-oncogenic viruses with animal cells consists in marked enhancement of production of proper cellular RNA and proteins in the infected cells and an increase in their division rate preceeding their death.", "contents": "[Cell proliferation induction in a monolayer chick embryo culture by the Sendai virus]. The response of cells on monolayer chick embryo cultures to infection with Sendai virus was studied. Total infection leads to the death of the cells within 3--5 days postinoculation which permits this system to be considered as lytic. Its significant difference from other systems with the lytic outcome of interaction of non-oncogenic viruses with animal cells consists in marked enhancement of production of proper cellular RNA and proteins in the infected cells and an increase in their division rate preceeding their death."}
{"id": "PMID:225881", "title": "[Relationship of the characteristics of the chromosome set in human cell cultures to the production and antiviral action of interferon].", "content": "The role of chromosomes 2, 5, 16, and 21 in production and effect of human interferon was checked in human diploid cells, human heteroploid cells J-96 and clone J-41 thereof. The J-41 cells were found to have a lower number of chromosomes 2 as compared to the other cells under study; J-41 cells produce less interferon than the other cells. Most J-41 cells lack chromosome 21. Unlike the other two cell cultures, these cells do not produce antivirus state after treatment with interferon. The number of chromosomes 16 is larger in J-96 cells than in diploid ones, and they are less sensitive to interferon than diploid cells. The experimental results confirm the importance of chromosome 2 for coding for interferon production, other chromosomes taking part in the regulation of this process. The gene of sensitivity to interferon is localized in chromosome 21, the regulator gene coding the production of repressor of sensitivity to interferon is in chromosome 16.", "contents": "[Relationship of the characteristics of the chromosome set in human cell cultures to the production and antiviral action of interferon]. The role of chromosomes 2, 5, 16, and 21 in production and effect of human interferon was checked in human diploid cells, human heteroploid cells J-96 and clone J-41 thereof. The J-41 cells were found to have a lower number of chromosomes 2 as compared to the other cells under study; J-41 cells produce less interferon than the other cells. Most J-41 cells lack chromosome 21. Unlike the other two cell cultures, these cells do not produce antivirus state after treatment with interferon. The number of chromosomes 16 is larger in J-96 cells than in diploid ones, and they are less sensitive to interferon than diploid cells. The experimental results confirm the importance of chromosome 2 for coding for interferon production, other chromosomes taking part in the regulation of this process. The gene of sensitivity to interferon is localized in chromosome 21, the regulator gene coding the production of repressor of sensitivity to interferon is in chromosome 16."}
{"id": "PMID:225882", "title": "[Experimental myocardiopathy caused by the herpesvirus].", "content": "Mice weighing 18--20 g were inoculated with herpes simplex virus type I. The rate of pathological changes in the myocardium was found to depend on the route of virus inoculation and the time of heart examinations in the infected animals. The development of myocardiopathies was not determined by the virus dose used in the test. An immunosuppressant drug, imurane, reduced the rate of heart affections. Pathomorphological changes in the heart were of parenchymatous-interstitial nature, with the leading role of lesions of myocardium muscle cells proper and secondary development of microcirculation disorders. The rate of heart lesions increased when herpes and influenza viruses were given to mice simultaneously; staphylococcus toxin had the same effect.", "contents": "[Experimental myocardiopathy caused by the herpesvirus]. Mice weighing 18--20 g were inoculated with herpes simplex virus type I. The rate of pathological changes in the myocardium was found to depend on the route of virus inoculation and the time of heart examinations in the infected animals. The development of myocardiopathies was not determined by the virus dose used in the test. An immunosuppressant drug, imurane, reduced the rate of heart affections. Pathomorphological changes in the heart were of parenchymatous-interstitial nature, with the leading role of lesions of myocardium muscle cells proper and secondary development of microcirculation disorders. The rate of heart lesions increased when herpes and influenza viruses were given to mice simultaneously; staphylococcus toxin had the same effect."}
{"id": "PMID:225883", "title": "[Possible mechanism of orthopoxvirus preservation in nature].", "content": "Until recently, virus carrier state in the absence of overt clinical infection has been known for only one species of orthopoxviruses, namely, ectromelia virus. The paper describes the results of the modelling of asypmtomatic infection caused by monkeypox, cowpox, and ratpox viruses. Persistence of these viruses up to 6 weeks in animals (hamsters, cotton and white rats) with experimental asymptomatic infection as well as in apparently normal naturally infected white rats was established by isolation of virus from the organs of these animals. These results suggest that asymptomatic virus carrier state may occur both with ectromelia and a number of other orthopoxviruses. The mechanism may be of ecological importance, providing for circulation of these viruses and their preservation as biological species in nature.", "contents": "[Possible mechanism of orthopoxvirus preservation in nature]. Until recently, virus carrier state in the absence of overt clinical infection has been known for only one species of orthopoxviruses, namely, ectromelia virus. The paper describes the results of the modelling of asypmtomatic infection caused by monkeypox, cowpox, and ratpox viruses. Persistence of these viruses up to 6 weeks in animals (hamsters, cotton and white rats) with experimental asymptomatic infection as well as in apparently normal naturally infected white rats was established by isolation of virus from the organs of these animals. These results suggest that asymptomatic virus carrier state may occur both with ectromelia and a number of other orthopoxviruses. The mechanism may be of ecological importance, providing for circulation of these viruses and their preservation as biological species in nature."}
{"id": "PMID:225884", "title": "[Physicochemical properties of the Okhotsky virus].", "content": "Purified concentrated Okhotsky virus was prepared. The buoyant densities of its virions were determined in sucrose and cesium chloride gradients and found to be 1.16--1.18 and 1.36 g/cm3, respectively. The experimental evidence indicated the double-stranded nature of Okhotsky virus genome RNA. The study of the above physico-chemical properties confirmed the appurtenance of Okhotsky virus to the genus Orbivirus of the Reoviridae family.", "contents": "[Physicochemical properties of the Okhotsky virus]. Purified concentrated Okhotsky virus was prepared. The buoyant densities of its virions were determined in sucrose and cesium chloride gradients and found to be 1.16--1.18 and 1.36 g/cm3, respectively. The experimental evidence indicated the double-stranded nature of Okhotsky virus genome RNA. The study of the above physico-chemical properties confirmed the appurtenance of Okhotsky virus to the genus Orbivirus of the Reoviridae family."}
{"id": "PMID:225885", "title": "[Virological and serological study of rotavirus gastroenteritis].", "content": "Cases of acute gastroenteritis with negative bacteriological analyses were examined. Preparations of feces collected from patients in the acute stage of the disease were found by immune electron microscopy to contain typical rotavirus particles forming specific aggregates in the presence of convalescent sera. Examinations of paired acute and convalescent sera of the patients revealed the presence in convalescent sera of specific antibodies neutralizing simian rotavirus SA 11 antigenically related to human rotavirus. The specificity of the antibody was confirmed by their titrations by immune electron microscopy and HI test. Thus, rotavirus etiology of cases of gastroenteritis in various parts of the country was confirmed, and the possibility of specific laboratory diagnosis of such cases using simian rotavirus SA 11 was demonstrated.", "contents": "[Virological and serological study of rotavirus gastroenteritis]. Cases of acute gastroenteritis with negative bacteriological analyses were examined. Preparations of feces collected from patients in the acute stage of the disease were found by immune electron microscopy to contain typical rotavirus particles forming specific aggregates in the presence of convalescent sera. Examinations of paired acute and convalescent sera of the patients revealed the presence in convalescent sera of specific antibodies neutralizing simian rotavirus SA 11 antigenically related to human rotavirus. The specificity of the antibody was confirmed by their titrations by immune electron microscopy and HI test. Thus, rotavirus etiology of cases of gastroenteritis in various parts of the country was confirmed, and the possibility of specific laboratory diagnosis of such cases using simian rotavirus SA 11 was demonstrated."}
{"id": "PMID:225886", "title": "[Human rotavirus in cell culture: its isolation and passage].", "content": "Rotavirus was isolated from feces of patients and passaged in green monkey kidney cell subculture using the factors affecting the initiation of infection of tissue culture cells with human rotavirus. The effective factors were found to include the presence of low concentrations of trypsin in the infected culture and virus centrifugation of a cell layer which agreed with the data by Almeida et al. (1978) and Shoub and Bertran (1978) obtained in other cell systems. Immune electron microscopy was used to detect the virus in cell cultures and to prove its specificity.", "contents": "[Human rotavirus in cell culture: its isolation and passage]. Rotavirus was isolated from feces of patients and passaged in green monkey kidney cell subculture using the factors affecting the initiation of infection of tissue culture cells with human rotavirus. The effective factors were found to include the presence of low concentrations of trypsin in the infected culture and virus centrifugation of a cell layer which agreed with the data by Almeida et al. (1978) and Shoub and Bertran (1978) obtained in other cell systems. Immune electron microscopy was used to detect the virus in cell cultures and to prove its specificity."}
{"id": "PMID:225892", "title": "[New aspects of diagnosis, treatment and follow-up of trophoblastic tumours (author's transl)].", "content": "Diagnosis, treatment and follow-up of gestational trophoblastic tumours has become more efficient through the introduction of new methods like angiography, computer tomography and, especially, the determination of specific chorionic gonadotrophin. Exact diagnosis, with differentiation of high- and low-risk patients allows an individual approach to treatment. The results of these new diagnostic and therapeutic methods were studied in a department with a relatively high incidence of gestational trophoblastic disease in a European region, where trophoblastic tumours are generally rare. (Since 1971 16 cases of trophoblastic tumour and 68 patients with hydatidiform mole were treated in the department of Obstetrics and Gynaecology, University of Graz.) Schedules were drawn up for the diagnosis, classification of risk and for treatment. This may help to get good results and to prevent errors in the future. Long-term determination of HCG beta in the serum and also comparative follow-up of LH and HCG in urine led to the formulation of further characteristics of gonadotrophin secretion after hydatidiform mole and treatment of trophoblastic tumours. On the basis of the results a regimen has been formulated which seems to be optimal for the detection of tumour after hydatidiform mole and for the registration of the effect of treatment in case of trophoblastic tumour.", "contents": "[New aspects of diagnosis, treatment and follow-up of trophoblastic tumours (author's transl)]. Diagnosis, treatment and follow-up of gestational trophoblastic tumours has become more efficient through the introduction of new methods like angiography, computer tomography and, especially, the determination of specific chorionic gonadotrophin. Exact diagnosis, with differentiation of high- and low-risk patients allows an individual approach to treatment. The results of these new diagnostic and therapeutic methods were studied in a department with a relatively high incidence of gestational trophoblastic disease in a European region, where trophoblastic tumours are generally rare. (Since 1971 16 cases of trophoblastic tumour and 68 patients with hydatidiform mole were treated in the department of Obstetrics and Gynaecology, University of Graz.) Schedules were drawn up for the diagnosis, classification of risk and for treatment. This may help to get good results and to prevent errors in the future. Long-term determination of HCG beta in the serum and also comparative follow-up of LH and HCG in urine led to the formulation of further characteristics of gonadotrophin secretion after hydatidiform mole and treatment of trophoblastic tumours. On the basis of the results a regimen has been formulated which seems to be optimal for the detection of tumour after hydatidiform mole and for the registration of the effect of treatment in case of trophoblastic tumour."}
{"id": "PMID:225894", "title": "[Immunology and oncology of paraproteins].", "content": "Since the first description by Apitz paraproteins were for a long time regarded as biologically abnormal proteins which normally do not appear in the human plasma. According to the modern biochemical knowledge this determination of the notion can no more be acknowledged, since analyses of amino acids did not reveal any differences in the composition of the complete paraproteins and the immune globulins. Apart from the complete paraproteins which consist either of gamma, my, delta, alpha or epsilon heavy chains on the one hand and of kappa or lambda easy chains on the other hand, also molecule fragments and isolated heavy or easy chains, respectively, appear. Like immune proteins paraproteins are formed by B-lymphocytes and their transformation forms, respectively, in which case the monoclonality represents their specific characteristic. Thus exist close relations to malignant changes of the B-lymphocyte system, in particular to the non-Hodgkin-lymphomas. Several functional peculiarities of the paraproteins, such as autoantibody effect, lymphocytotoxicity, aggregation ability and binding affinity to blood cells lead to multiform clinical phenomena. To this belong immune defects, nephropathies, haemocytopenias, amyloidoses and haemorrhagic diatheses. As evoking cause of the alteration of B-lymphocyte system with activation of one or several cell clones (e.g. in double paraproteinaemia) tumour viruses are taken into consideration. After an infection with oncogenic herpes viruses irreversible cell transformations in the lymphatic system have been proved. Thus it is doubtful, whether there are indeed true benign paraproteinaemias. One has rather to speak only of relatively benign forms of the course.", "contents": "[Immunology and oncology of paraproteins]. Since the first description by Apitz paraproteins were for a long time regarded as biologically abnormal proteins which normally do not appear in the human plasma. According to the modern biochemical knowledge this determination of the notion can no more be acknowledged, since analyses of amino acids did not reveal any differences in the composition of the complete paraproteins and the immune globulins. Apart from the complete paraproteins which consist either of gamma, my, delta, alpha or epsilon heavy chains on the one hand and of kappa or lambda easy chains on the other hand, also molecule fragments and isolated heavy or easy chains, respectively, appear. Like immune proteins paraproteins are formed by B-lymphocytes and their transformation forms, respectively, in which case the monoclonality represents their specific characteristic. Thus exist close relations to malignant changes of the B-lymphocyte system, in particular to the non-Hodgkin-lymphomas. Several functional peculiarities of the paraproteins, such as autoantibody effect, lymphocytotoxicity, aggregation ability and binding affinity to blood cells lead to multiform clinical phenomena. To this belong immune defects, nephropathies, haemocytopenias, amyloidoses and haemorrhagic diatheses. As evoking cause of the alteration of B-lymphocyte system with activation of one or several cell clones (e.g. in double paraproteinaemia) tumour viruses are taken into consideration. After an infection with oncogenic herpes viruses irreversible cell transformations in the lymphatic system have been proved. Thus it is doubtful, whether there are indeed true benign paraproteinaemias. One has rather to speak only of relatively benign forms of the course."}
{"id": "PMID:225887", "title": "[IgG- and IgA-antibodies to the Epstein-Barr virus in the sera of patients with nasopharyngeal carcinoma in Cuba].", "content": "Sera from 24 patients with nasopharyngeal carcinoma (NPC) and from 60 normal subjects were examined for the presence of IgG and IgA antibody to various antigens associated with Epstein-Barr virus (EBV). The results indicate that NPC in Cuba, like in other countries, was accompanied by high titers of EBV-specific IgG antibody the levels of which differed markedly from those in normal subjects. Serological activity of the patients differed depending on the stage of the illness and its duration. Geometric mean antibody titers to the capsid antigen (VCA), D and R components of early antigen (EA) of EBV complex were higher in patients with extensive tumour process (III--IV stages) and in patients with the duration of the disease since the onset less than 3 years. Sera of the most patients contained EBV-specific IgA antibody which were practically completely absent in sera of the control subjects. Alongside with characteristic manifestations of responsiveness to EBV observed by other workers, patients with NPC in Cuba had specific features: higher antibody titers to VCA than in Caucasian subjects in the countries where this disease occurred sporadically, like in Cuba; high levels of antibody to EA, frequently exceeding those in patients with NPC from endemic zones (for instance in Chinese patients); prevalence of EBV-specific antibody to the R component of EA complex.", "contents": "[IgG- and IgA-antibodies to the Epstein-Barr virus in the sera of patients with nasopharyngeal carcinoma in Cuba]. Sera from 24 patients with nasopharyngeal carcinoma (NPC) and from 60 normal subjects were examined for the presence of IgG and IgA antibody to various antigens associated with Epstein-Barr virus (EBV). The results indicate that NPC in Cuba, like in other countries, was accompanied by high titers of EBV-specific IgG antibody the levels of which differed markedly from those in normal subjects. Serological activity of the patients differed depending on the stage of the illness and its duration. Geometric mean antibody titers to the capsid antigen (VCA), D and R components of early antigen (EA) of EBV complex were higher in patients with extensive tumour process (III--IV stages) and in patients with the duration of the disease since the onset less than 3 years. Sera of the most patients contained EBV-specific IgA antibody which were practically completely absent in sera of the control subjects. Alongside with characteristic manifestations of responsiveness to EBV observed by other workers, patients with NPC in Cuba had specific features: higher antibody titers to VCA than in Caucasian subjects in the countries where this disease occurred sporadically, like in Cuba; high levels of antibody to EA, frequently exceeding those in patients with NPC from endemic zones (for instance in Chinese patients); prevalence of EBV-specific antibody to the R component of EA complex."}
{"id": "PMID:225888", "title": "[Levels of humoral antibodies to Epstein-Barr virus in the population of Cuba].", "content": "Indirect immunofluorescence was used to study the levels of humoral antibodies to capsid (VCA) and early (EA) antigens of Epstein-Barr virus (EBV) in sera of 322 normal subjects living in the province of Habana and varying in ages from several months to 93 years. The results suggest that the population of Cuba, like in other countries, is widely infected with EBV, although the pattern of spread of this infection has some specific features. In particular, the infection rate of the pediatric population (3--4 and 5--9 years) is moderately high, 73% and 65%, respectively, whereas in adult population it is rather low (62--86%) despite the tropical location of the country. In all the age groups examined, geometric mean titers (GMT) of antibody to VCA were also lower than in comparable groups of population from other countries. The observed high GMT of VCA antibody in persons over 55 years and a considerable increase in the number of positively reacting sera and sera with high antibody titers (greater than or equal to 1 : 160) agree with the data by other workers and appear to be due to reduced immunological defence of the cellular type in elderly people. Antibody to EBV EA were found in all the age groups examined, although in a small per cent. The subjects with high antibody titers to this antigen (greater than or equal to 1 : 40) were found more frequently in the two youngest age groups (0--2 and 3--4 years) which appears to be due to large amounts of virus usually occuring in the period of primary infection. The analysis of infectious mononucleosis incidence for 5 years (1972--1976) in various age groups of Habana province population indicates a general low level of incidence. Two small peaks in 3--4 and 15--19-year groups corresponded to increased GMT values of antibody to EBV EA in these particular age groups.", "contents": "[Levels of humoral antibodies to Epstein-Barr virus in the population of Cuba]. Indirect immunofluorescence was used to study the levels of humoral antibodies to capsid (VCA) and early (EA) antigens of Epstein-Barr virus (EBV) in sera of 322 normal subjects living in the province of Habana and varying in ages from several months to 93 years. The results suggest that the population of Cuba, like in other countries, is widely infected with EBV, although the pattern of spread of this infection has some specific features. In particular, the infection rate of the pediatric population (3--4 and 5--9 years) is moderately high, 73% and 65%, respectively, whereas in adult population it is rather low (62--86%) despite the tropical location of the country. In all the age groups examined, geometric mean titers (GMT) of antibody to VCA were also lower than in comparable groups of population from other countries. The observed high GMT of VCA antibody in persons over 55 years and a considerable increase in the number of positively reacting sera and sera with high antibody titers (greater than or equal to 1 : 160) agree with the data by other workers and appear to be due to reduced immunological defence of the cellular type in elderly people. Antibody to EBV EA were found in all the age groups examined, although in a small per cent. The subjects with high antibody titers to this antigen (greater than or equal to 1 : 40) were found more frequently in the two youngest age groups (0--2 and 3--4 years) which appears to be due to large amounts of virus usually occuring in the period of primary infection. The analysis of infectious mononucleosis incidence for 5 years (1972--1976) in various age groups of Habana province population indicates a general low level of incidence. Two small peaks in 3--4 and 15--19-year groups corresponded to increased GMT values of antibody to EBV EA in these particular age groups."}
{"id": "PMID:225895", "title": "[Plasma lipoproteins and apolipoproteins].", "content": "In a survey the plasmalipoproteins LDL, VLDL and HDL are characterized and their functions demonstrated. Metabolically they are connected together through the IDL. Their clinical importance lies in the disturbances of the lipoprotein metabolism, which are significant for hyperlipoproteinaemia and arteriosclerotic diseases. Atypical plasmalipoproteins are LP(a), pre-beta-1-lipoprotein and sinking-pre-beta-lipoproteins. The LP-X is of interest for the differential diagnosis of jaundice. The carrier proteins of the plasmalipoproteins, the apolipoproteins, are Apo A, Apo B, Apo C, Apo D, and Apo E. They are differently structured. Their concentration in the individual plasmalipoproteins are also responsible for their function in normal and pathological lipid metabolism.", "contents": "[Plasma lipoproteins and apolipoproteins]. In a survey the plasmalipoproteins LDL, VLDL and HDL are characterized and their functions demonstrated. Metabolically they are connected together through the IDL. Their clinical importance lies in the disturbances of the lipoprotein metabolism, which are significant for hyperlipoproteinaemia and arteriosclerotic diseases. Atypical plasmalipoproteins are LP(a), pre-beta-1-lipoprotein and sinking-pre-beta-lipoproteins. The LP-X is of interest for the differential diagnosis of jaundice. The carrier proteins of the plasmalipoproteins, the apolipoproteins, are Apo A, Apo B, Apo C, Apo D, and Apo E. They are differently structured. Their concentration in the individual plasmalipoproteins are also responsible for their function in normal and pathological lipid metabolism."}
{"id": "PMID:225897", "title": "[The effect of theophyllin on small intestinal structure and function of the diabetic rat (author's transl)].", "content": "In order to obtain some information about the role of cAMP in the regulation of cell turnover of the intestinal mucosa it was interesting to investigate whether chronic pharmacologically induced changes in the cellular cAMP levels could cause alterations in mucosal growth in the case of a well defined animal modell, involving increased cell proliferation rate, such as chronic experimental diabetes mellitus of the rat. Since it has been suggested that cAMP levels on the one hand are low in cell division and increased cAMP levels on the other hand inhibit cell division, the aim of the study was to induce a suppression of the cell proliferation rate in the intestinal mucosa by chronic theophyllin application, a well known PDE-inhibitor. The following results could be obtained: Chronic theophyllin application induces a hyperplastic alteration of the small intestinal mucosa of the rat, which is similar to that observed in diabetes mellitus. In diabetic animals theophyllin causes a further increase in hyperplasia. The morphological alterations of the intestinal mucosa are more pronounced than the functional changes. In experimental diabetes mellitus the radioimmunologically determined cAMP level in the intestinal mucosa is rather low. Chronic theophyllin application alone or in combination with experimental diabetes mellitus was unable to increase the cAMP-level continuously. This could be a result of an adaptive change of the cAMP regulating enzyme system. Therefore theophyllin induced mucosal alterations are probably due to systemic effects of this drug.", "contents": "[The effect of theophyllin on small intestinal structure and function of the diabetic rat (author's transl)]. In order to obtain some information about the role of cAMP in the regulation of cell turnover of the intestinal mucosa it was interesting to investigate whether chronic pharmacologically induced changes in the cellular cAMP levels could cause alterations in mucosal growth in the case of a well defined animal modell, involving increased cell proliferation rate, such as chronic experimental diabetes mellitus of the rat. Since it has been suggested that cAMP levels on the one hand are low in cell division and increased cAMP levels on the other hand inhibit cell division, the aim of the study was to induce a suppression of the cell proliferation rate in the intestinal mucosa by chronic theophyllin application, a well known PDE-inhibitor. The following results could be obtained: Chronic theophyllin application induces a hyperplastic alteration of the small intestinal mucosa of the rat, which is similar to that observed in diabetes mellitus. In diabetic animals theophyllin causes a further increase in hyperplasia. The morphological alterations of the intestinal mucosa are more pronounced than the functional changes. In experimental diabetes mellitus the radioimmunologically determined cAMP level in the intestinal mucosa is rather low. Chronic theophyllin application alone or in combination with experimental diabetes mellitus was unable to increase the cAMP-level continuously. This could be a result of an adaptive change of the cAMP regulating enzyme system. Therefore theophyllin induced mucosal alterations are probably due to systemic effects of this drug."}
{"id": "PMID:225898", "title": "[Information regulation in the vegetative periphery].", "content": "The importance of the proteoglycans (PG) of the extracellular matrix in regulating the information reaching the vegetative periphery is demonstrated. Information brought to the vegetative periphery by autonomic nerves and the microcirculatory system are coded by the PG, thereby changing their biochemical structure. These changes (i.e. degree of polymerisation, capacity of ion-exchange and water-binding, electrostatical tonus) stimulate via the specific cellglycocalyx the cAMP-adenylcyclase-system of the cells in the vegetative periphery. In this way the information becomes decoded and is followed by the enzymatically steered answer of the cell. The center for all of these relations is the fibrocyte. The fibrocytes form the metabolic active center in the vegetative periphery and answer to \"informative\" changes in the extracellular matrix with a situation-dependent synthesis of PG. The possibilities of modulating the intercellular transfer of informations --- various cell contacts, temporary intercytoplasmic connections (fusomes), the role of mastcells.", "contents": "[Information regulation in the vegetative periphery]. The importance of the proteoglycans (PG) of the extracellular matrix in regulating the information reaching the vegetative periphery is demonstrated. Information brought to the vegetative periphery by autonomic nerves and the microcirculatory system are coded by the PG, thereby changing their biochemical structure. These changes (i.e. degree of polymerisation, capacity of ion-exchange and water-binding, electrostatical tonus) stimulate via the specific cellglycocalyx the cAMP-adenylcyclase-system of the cells in the vegetative periphery. In this way the information becomes decoded and is followed by the enzymatically steered answer of the cell. The center for all of these relations is the fibrocyte. The fibrocytes form the metabolic active center in the vegetative periphery and answer to \"informative\" changes in the extracellular matrix with a situation-dependent synthesis of PG. The possibilities of modulating the intercellular transfer of informations --- various cell contacts, temporary intercytoplasmic connections (fusomes), the role of mastcells."}
{"id": "PMID:225906", "title": "[Effects of zinc-aerosols on the inhalation toxicity of cadmium (author's transl)].", "content": "Female rats were continuously exposed for 3 months to an aerosol containing 50 micrograms/m3 Cadmium-Oxyd and 1.25 mg/m3 Zinc-Oxyd. Our results were compared with those of Prigge (1977), who studied the CdO-toxicity under equal conditions. Inour investigations we studied with clinical and clinico-chemical methods a possible protective effect of ZnO on the Cd-toxicity, given simultanously. A protective effect of ZnO on the Cd-toxicity was evident in out investigations in form of a reduced deposition of Cd in lungs, in livers and kidneys. A reduction of the cadmium-induced hyperplasia of lungs was a remarkable sign for a protective action of Zn. There are some criterions, that Zn, given simultaneously in the studied concentrations, can inhibit the Cd-induced disorder of function in kidneys.", "contents": "[Effects of zinc-aerosols on the inhalation toxicity of cadmium (author's transl)]. Female rats were continuously exposed for 3 months to an aerosol containing 50 micrograms/m3 Cadmium-Oxyd and 1.25 mg/m3 Zinc-Oxyd. Our results were compared with those of Prigge (1977), who studied the CdO-toxicity under equal conditions. Inour investigations we studied with clinical and clinico-chemical methods a possible protective effect of ZnO on the Cd-toxicity, given simultanously. A protective effect of ZnO on the Cd-toxicity was evident in out investigations in form of a reduced deposition of Cd in lungs, in livers and kidneys. A reduction of the cadmium-induced hyperplasia of lungs was a remarkable sign for a protective action of Zn. There are some criterions, that Zn, given simultaneously in the studied concentrations, can inhibit the Cd-induced disorder of function in kidneys."}
{"id": "PMID:225910", "title": "[Immunologic aspects of the pathogenesis and treatment of myasthenia].", "content": "In 30 myasthenic patients the state of the T and B systems of immunity was examined: Depending on the initial findings the immunodepressant therapy (gamma-irradiation of the thymus, intrathymic blockades with hydrocortisone, ultraphonophoresis of hydrocortisone into the thymus area, oral administration of imuran, and intramuscular injections of antilymphocytic immunoglobulin) was given. A relationship between the immunological changes and the disease stage was discovered: the index of the 3H-thymidine incorporation was found to be 67.9 at the stage of disease exacerbation, and 208.8 at the stage of remission; the complement titre reached, respectively, 46.64 +/- 5.28 and 112.0 +/- 6.0 units per ml. The different methods of the immunodepressant therapy produced different effects on the patients' state and the immunological shifts. The combination of hydrocortisone with imuran appeared to be the most sparing and sufficiently efficacious method of the therapy.", "contents": "[Immunologic aspects of the pathogenesis and treatment of myasthenia]. In 30 myasthenic patients the state of the T and B systems of immunity was examined: Depending on the initial findings the immunodepressant therapy (gamma-irradiation of the thymus, intrathymic blockades with hydrocortisone, ultraphonophoresis of hydrocortisone into the thymus area, oral administration of imuran, and intramuscular injections of antilymphocytic immunoglobulin) was given. A relationship between the immunological changes and the disease stage was discovered: the index of the 3H-thymidine incorporation was found to be 67.9 at the stage of disease exacerbation, and 208.8 at the stage of remission; the complement titre reached, respectively, 46.64 +/- 5.28 and 112.0 +/- 6.0 units per ml. The different methods of the immunodepressant therapy produced different effects on the patients' state and the immunological shifts. The combination of hydrocortisone with imuran appeared to be the most sparing and sufficiently efficacious method of the therapy."}
{"id": "PMID:225912", "title": "[Diagnosis of lesions of the ilioinguinal nerve using clinical and electromyographic methods].", "content": "On the basis of a study of 11 normals and 19 patients, the clinical and EMG features of iloinguinal nerve lesions are described. In lesions of this nerve there are EMG changes in the internal oblique abdominal muscles, which indicate an involvement into the pathological process of not only of the nerve conductors, but central structures. The EMG method may be recommended as a supplementary one for detecting subclinical forms of the disease, clarification of the diagnosis and determination of the degree of nerve lesions.", "contents": "[Diagnosis of lesions of the ilioinguinal nerve using clinical and electromyographic methods]. On the basis of a study of 11 normals and 19 patients, the clinical and EMG features of iloinguinal nerve lesions are described. In lesions of this nerve there are EMG changes in the internal oblique abdominal muscles, which indicate an involvement into the pathological process of not only of the nerve conductors, but central structures. The EMG method may be recommended as a supplementary one for detecting subclinical forms of the disease, clarification of the diagnosis and determination of the degree of nerve lesions."}
{"id": "PMID:225915", "title": "Serum trypsin inhibitory capacity and alpha 1-antitrypsin levels in liver cirrhosis and hepatoma.", "content": "alpha 1-Antitrypsin levels were measured in sera of 134 patients with cirrhosis and in 64 with cirrhosis and hepatoma. S-TIC was determined in 105 patients with cirrhosis and in 54 with cirrhosis and hepatoma. The mean alpha 1-at and S-TIC values in patients with cirrhosis were 369.59 +/- 14.072 mg% and 1,808 +/- 0.05 mg/ml respectively. In patients with cirrhosis and hepatoma the mean alpha 1-at level was 406.595 +/- 17.834 mg% and the S-TIC mean values was 2.064 +/- 0.82 mg/ml. Although these values are higher than those found in the healthy controls, the differences are not statistically significant.", "contents": "Serum trypsin inhibitory capacity and alpha 1-antitrypsin levels in liver cirrhosis and hepatoma. alpha 1-Antitrypsin levels were measured in sera of 134 patients with cirrhosis and in 64 with cirrhosis and hepatoma. S-TIC was determined in 105 patients with cirrhosis and in 54 with cirrhosis and hepatoma. The mean alpha 1-at and S-TIC values in patients with cirrhosis were 369.59 +/- 14.072 mg% and 1,808 +/- 0.05 mg/ml respectively. In patients with cirrhosis and hepatoma the mean alpha 1-at level was 406.595 +/- 17.834 mg% and the S-TIC mean values was 2.064 +/- 0.82 mg/ml. Although these values are higher than those found in the healthy controls, the differences are not statistically significant."}
{"id": "PMID:225916", "title": "Changes of serum angiotensin I converting enzyme in patients with viral hepatitis and liver cirrhosis.", "content": "Serum angiotensin I converting enzyme, identical with kininase II, was measured fluorometrically in patients with acute viral hepatitis (n=18), liver cirrhosis without (n=44) and with (n=19) ascites. In all groups of patients the enzyme was significantly elevated as compared to 44 healthy controls (p less than 0.001). No correlation could be found between angiotensin I converting enzyme activity and liver function tests (serum glutamic oxalacetic transaminase, serum glutamic pyruvic transaminase, total protein, albumin, bilirubin) or other parameters (serum potassium, serum sodium). High serum converting enzyme activity in chronic liver diseases might originate primarily from an altered pulmonary circulation and indicates higher conversion rate of angiotensin I by passage through the lungs as well as increased bradykinin degradation. The reason for the enzyme liberation in acute viral hepatitis is as yet uncertain.", "contents": "Changes of serum angiotensin I converting enzyme in patients with viral hepatitis and liver cirrhosis. Serum angiotensin I converting enzyme, identical with kininase II, was measured fluorometrically in patients with acute viral hepatitis (n=18), liver cirrhosis without (n=44) and with (n=19) ascites. In all groups of patients the enzyme was significantly elevated as compared to 44 healthy controls (p less than 0.001). No correlation could be found between angiotensin I converting enzyme activity and liver function tests (serum glutamic oxalacetic transaminase, serum glutamic pyruvic transaminase, total protein, albumin, bilirubin) or other parameters (serum potassium, serum sodium). High serum converting enzyme activity in chronic liver diseases might originate primarily from an altered pulmonary circulation and indicates higher conversion rate of angiotensin I by passage through the lungs as well as increased bradykinin degradation. The reason for the enzyme liberation in acute viral hepatitis is as yet uncertain."}
{"id": "PMID:225913", "title": "[Determination of the individual sensitivity of human glial tumors to the action of chemotherapeutic preparations].", "content": "Individual sensitivity of 40 glial tumors (34 macroglial and 5 oligodendroglial tumors and 1 medulloblastoma) to 4 chemotherapeutical agents (fluorofur, 5-fluorouracil, methotrexate and sarcolysin) was studied in vitro on the basis of changes in the values of thymidine labelling index after 24-hour incubation of tumor-tissue fragments in a medium with the chemical agents. Each of the tumors studied possessed individual range of sensitivity to the chemotherapeutical agents distinguishing it from other tumors. None of the agents studied proved to more effective than others. The reaction of the tumor tissue to the effect of the chemotherapeutical agents did not depend on the proliferative activity of the tumor, while the degree of manifestation of the tumor reaction was often dependent on the concentration of the agents. An increase in the number of DNA-synthesizing cells in the tumor under the effect of the chemical agents was observed in rare cases.", "contents": "[Determination of the individual sensitivity of human glial tumors to the action of chemotherapeutic preparations]. Individual sensitivity of 40 glial tumors (34 macroglial and 5 oligodendroglial tumors and 1 medulloblastoma) to 4 chemotherapeutical agents (fluorofur, 5-fluorouracil, methotrexate and sarcolysin) was studied in vitro on the basis of changes in the values of thymidine labelling index after 24-hour incubation of tumor-tissue fragments in a medium with the chemical agents. Each of the tumors studied possessed individual range of sensitivity to the chemotherapeutical agents distinguishing it from other tumors. None of the agents studied proved to more effective than others. The reaction of the tumor tissue to the effect of the chemotherapeutical agents did not depend on the proliferative activity of the tumor, while the degree of manifestation of the tumor reaction was often dependent on the concentration of the agents. An increase in the number of DNA-synthesizing cells in the tumor under the effect of the chemical agents was observed in rare cases."}
{"id": "PMID:225917", "title": "Hepatocellular carcinoma associated with erythrocytosis. A nine year survival after successful chemotherapy and left lateral hepatectomy.", "content": "A case of hepatocellular carcinoma associated with erythrocytosis is described. The patient was successfully treated with a combination chemotherapy of 5-fluorouracil, mitomycin C, cyclophosphamide and chromomycin A3, which was followed by a left lateral hepatectomy, and has survived for more than 9 years after the operation without any signs of recurrence. With the regression of hepatic tumor by the anticancer chemotherapy, the remission of erythrocytosis was observed, indicating that the tumor was producing erythropoietin. The data suggest also that erythrocytosis could be a marker for evaluation of chemotherapeutic effects in some patients with hepatocellular carcinoma.", "contents": "Hepatocellular carcinoma associated with erythrocytosis. A nine year survival after successful chemotherapy and left lateral hepatectomy. A case of hepatocellular carcinoma associated with erythrocytosis is described. The patient was successfully treated with a combination chemotherapy of 5-fluorouracil, mitomycin C, cyclophosphamide and chromomycin A3, which was followed by a left lateral hepatectomy, and has survived for more than 9 years after the operation without any signs of recurrence. With the regression of hepatic tumor by the anticancer chemotherapy, the remission of erythrocytosis was observed, indicating that the tumor was producing erythropoietin. The data suggest also that erythrocytosis could be a marker for evaluation of chemotherapeutic effects in some patients with hepatocellular carcinoma."}
{"id": "PMID:225914", "title": "[Intracranial cylindroma (cylindromatous epithelioma)].", "content": "A case with intracranial cylindroma is reported. Intracranial cylindroma possesses local destructive growth and may recur repeatedly and produce metastases; it is localized on the base of the skull in the chiasmal area or, more frequently, in the region of the trigeminal ganglion. Cylindroma of chiasmal localization develops from ectopic mucous glands of the nose or nasal sinuses, whereas cylindroma of the trigeminal ganglion arises from the glandular epithelium of the auditory tube. Intracranial cylindroma is sensitive to radiation therapy. In the case discussed, the cylindroma was localized in the chiasmal area.", "contents": "[Intracranial cylindroma (cylindromatous epithelioma)]. A case with intracranial cylindroma is reported. Intracranial cylindroma possesses local destructive growth and may recur repeatedly and produce metastases; it is localized on the base of the skull in the chiasmal area or, more frequently, in the region of the trigeminal ganglion. Cylindroma of chiasmal localization develops from ectopic mucous glands of the nose or nasal sinuses, whereas cylindroma of the trigeminal ganglion arises from the glandular epithelium of the auditory tube. Intracranial cylindroma is sensitive to radiation therapy. In the case discussed, the cylindroma was localized in the chiasmal area."}
{"id": "PMID:225919", "title": "An electron microscopic study of childhood dermatomyositis.", "content": "Muscle biopsies from 12 patients with a typical clinical picture of dermatomyositis have been examined by electron microscopy. Endothelial cells of intramuscular blood vessels, their basal lamina, pericytes, muscle fibers, and satellite cells show degenerative or regenerative alterations. In nine patients, tubular arrays were noted in the cisterns of endoplasmic reticulum of endothelial cells, pericytes, lymphocytes, macrophages and satellite cells. Other types of inclusions were also observed. The pathogenesis of the disease is discussed.", "contents": "An electron microscopic study of childhood dermatomyositis. Muscle biopsies from 12 patients with a typical clinical picture of dermatomyositis have been examined by electron microscopy. Endothelial cells of intramuscular blood vessels, their basal lamina, pericytes, muscle fibers, and satellite cells show degenerative or regenerative alterations. In nine patients, tubular arrays were noted in the cisterns of endoplasmic reticulum of endothelial cells, pericytes, lymphocytes, macrophages and satellite cells. Other types of inclusions were also observed. The pathogenesis of the disease is discussed."}
{"id": "PMID:225920", "title": "Clioquinol and 2,5-hexanedione induce different types of distal axonopathy in the dog.", "content": "The central distal axonopathy induced in dogs by the administration of high doses of clioquinol is contrasted with the central-peripheral distal axonopathy precipitated by intoxication with 2,5-hexanedione. Mature, pure-bred Beagle dogs received a daily oral dose of 400 mg/kg of clioquinol for up to 7 months, or 1 ml per animal (approximately corresponding to 110 mg/kg) of 2,5-hexanedione for up to 5 months. Intoxicated and control animal were killed and perfused at monthly intervals, so that the spatial-temporal development of the lesion could be followed and correlated with clinical symptoms. During the treatment, dogs intoxicated with 2,5-hexanedione developed symptoms of peripheral neuropathy consisting of flaccid weakness, muscle atrophy, hind-limb foot-drop and areflexia. By contrast, the dogs surviving clioquinol intoxication exhibited a stiff-legged gait, hyperreflexia but no muscle atrophy. Light and electron microscope examination of central and peripheral nervous tissue from dogs intoxicated with 2,5-hexanedione revealed giant axonal swelling and distal axonal degeneration. By contrast, dogs receiving clioquinol showed a distal axonal degeneration confined to the optic tract and the long spinal cord tracts, without any visible involvement of peripheral nerves.", "contents": "Clioquinol and 2,5-hexanedione induce different types of distal axonopathy in the dog. The central distal axonopathy induced in dogs by the administration of high doses of clioquinol is contrasted with the central-peripheral distal axonopathy precipitated by intoxication with 2,5-hexanedione. Mature, pure-bred Beagle dogs received a daily oral dose of 400 mg/kg of clioquinol for up to 7 months, or 1 ml per animal (approximately corresponding to 110 mg/kg) of 2,5-hexanedione for up to 5 months. Intoxicated and control animal were killed and perfused at monthly intervals, so that the spatial-temporal development of the lesion could be followed and correlated with clinical symptoms. During the treatment, dogs intoxicated with 2,5-hexanedione developed symptoms of peripheral neuropathy consisting of flaccid weakness, muscle atrophy, hind-limb foot-drop and areflexia. By contrast, the dogs surviving clioquinol intoxication exhibited a stiff-legged gait, hyperreflexia but no muscle atrophy. Light and electron microscope examination of central and peripheral nervous tissue from dogs intoxicated with 2,5-hexanedione revealed giant axonal swelling and distal axonal degeneration. By contrast, dogs receiving clioquinol showed a distal axonal degeneration confined to the optic tract and the long spinal cord tracts, without any visible involvement of peripheral nerves."}
{"id": "PMID:225921", "title": "Crystalloid inclusions reminiscent of Hirano bodies in autolyzed peripheral nerve of normal wistar rats.", "content": "In a study of experimental autolysis of peripheral nerves of normal Wistar rats, crystalloid inclusions similar to Hirano bodies were observed. They occurred in the nuclei and cytoplasms of Schwann cells and in myelinated axons. They first developed after a 12-h autolysis and increased in number and size with time. Their fine structure, localization, and morphogenesis are discussed in relation to the autolysis of the cellular organelles.", "contents": "Crystalloid inclusions reminiscent of Hirano bodies in autolyzed peripheral nerve of normal wistar rats. In a study of experimental autolysis of peripheral nerves of normal Wistar rats, crystalloid inclusions similar to Hirano bodies were observed. They occurred in the nuclei and cytoplasms of Schwann cells and in myelinated axons. They first developed after a 12-h autolysis and increased in number and size with time. Their fine structure, localization, and morphogenesis are discussed in relation to the autolysis of the cellular organelles."}
{"id": "PMID:225922", "title": "Herpes simplex type 2 encephalitis concurrent with known cerebral metastases.", "content": "A 62-year-old woman developed neurologic deficits 7 months after pulmonary lobectomy for alveolar cell carcinoma of the lung. CT scan of the head demonstrated two metastases with marked peritumoral edema. Administration of Decadron, chemotherapy and 3,000 rad cranial radiation resulted in dramatic improvement of dysphasia and right hand paresis. Almost 2 months later, rhythmic, involuntary movements of the left hand developed. There was progression to multifocal seizures, grand mal seizures, postictal depression, status epilepticus, and coma, with death 9 days after onset of the movement disorder. Bronchoalveolar carcinoma was widely disseminated in lungs and bones, and as three metastases in brain. Bland \"ischemic\" necrosis in a pseudolaminar pattern was present in the neocortex. Innumerable Cowdry type A intranuclear inclusion bodies were seen in neurons, astrocytes, and oligodenodroglia. Immunofluorescence demonstrated Herpes simplex virus type 2 antigen and electron microscopy revealed virions with the morphology of the Herpes group. The case is significant for (1) the concurrence of intracranial metastases and Herpes simplex encephalitis, and (2) the causal agent, Herpes simplex virus type 2. The implication for the clinical neurocientist is the potential in a patient with systemic cancer, for the causation of neurologic complications by more than one factor or mechanism.", "contents": "Herpes simplex type 2 encephalitis concurrent with known cerebral metastases. A 62-year-old woman developed neurologic deficits 7 months after pulmonary lobectomy for alveolar cell carcinoma of the lung. CT scan of the head demonstrated two metastases with marked peritumoral edema. Administration of Decadron, chemotherapy and 3,000 rad cranial radiation resulted in dramatic improvement of dysphasia and right hand paresis. Almost 2 months later, rhythmic, involuntary movements of the left hand developed. There was progression to multifocal seizures, grand mal seizures, postictal depression, status epilepticus, and coma, with death 9 days after onset of the movement disorder. Bronchoalveolar carcinoma was widely disseminated in lungs and bones, and as three metastases in brain. Bland \"ischemic\" necrosis in a pseudolaminar pattern was present in the neocortex. Innumerable Cowdry type A intranuclear inclusion bodies were seen in neurons, astrocytes, and oligodenodroglia. Immunofluorescence demonstrated Herpes simplex virus type 2 antigen and electron microscopy revealed virions with the morphology of the Herpes group. The case is significant for (1) the concurrence of intracranial metastases and Herpes simplex encephalitis, and (2) the causal agent, Herpes simplex virus type 2. The implication for the clinical neurocientist is the potential in a patient with systemic cancer, for the causation of neurologic complications by more than one factor or mechanism."}
{"id": "PMID:225923", "title": "Sendai virus haemolysis: mechanism of the increased haemolysis obtained by pretreatment of the virus with antibody and complement.", "content": "Sendai virus is haemolytic against erythrocytes from various species. Pretreatment of the virus with antibody and complement (C) resulted in a sixfold increase in the haemolysis. The viral haemolysin (HL) could be inactivated by heating the virus at 37 degrees C for 5 h. HL-inactivated virus became haemolytic again when pre-treated with antibody and C. This acquired haemolytic capacity corresponded to the enhanced haemolysis shown by intact virus. It is concluded that the enhanced haemolytic activity is due to a C-mediated indirect haemolysis and is not dependent on the fusion process. The possibility of cell damage in vivo from virus-antibody-C complexes is discussed.", "contents": "Sendai virus haemolysis: mechanism of the increased haemolysis obtained by pretreatment of the virus with antibody and complement. Sendai virus is haemolytic against erythrocytes from various species. Pretreatment of the virus with antibody and complement (C) resulted in a sixfold increase in the haemolysis. The viral haemolysin (HL) could be inactivated by heating the virus at 37 degrees C for 5 h. HL-inactivated virus became haemolytic again when pre-treated with antibody and C. This acquired haemolytic capacity corresponded to the enhanced haemolysis shown by intact virus. It is concluded that the enhanced haemolytic activity is due to a C-mediated indirect haemolysis and is not dependent on the fusion process. The possibility of cell damage in vivo from virus-antibody-C complexes is discussed."}
{"id": "PMID:225924", "title": "Fractionation of connective-tissue-activating factors from the culture medium of silica-treated macrophages.", "content": "The medium of cultured, SiO2-treated peritoneal macrophages contained a factor which enhances the incorporation of labelled proline to collagen and other proteins in granulation tissue slices, cells and polysomes. Simultaneously, the activity of alkaline RNase in the whole medium was decreased in comparison with the corresponding control. Polyvinylpyridine-N-oxide, PVNO, protected the macrophages against SiO2. Latex-particles and E. coli lipopolysaccharide decreased the RNase activity in the macrophage medium, but unlike SiO2 did not cause liberation of the collagen synthesis-stimulating factor. Fractionation of the medium by gel filtration chromatography showed the SiO2-pretreatment to have caused a very significant decrease in the aggregation state of RNase. The fraction from gel filtration chromatography that contained the SiO2-liberated factor stimulating collagen synthesis also contained the disaggregated RNase. There was no RNase-activity in the control sample. A homogenous protein (mol. wt. 14,300) was isolated with repeated gel filtrations from the medium of silica-treated macrophages. It increased the incorporation of 3H proline and 3H thymidine into cultured granuloma cells.", "contents": "Fractionation of connective-tissue-activating factors from the culture medium of silica-treated macrophages. The medium of cultured, SiO2-treated peritoneal macrophages contained a factor which enhances the incorporation of labelled proline to collagen and other proteins in granulation tissue slices, cells and polysomes. Simultaneously, the activity of alkaline RNase in the whole medium was decreased in comparison with the corresponding control. Polyvinylpyridine-N-oxide, PVNO, protected the macrophages against SiO2. Latex-particles and E. coli lipopolysaccharide decreased the RNase activity in the macrophage medium, but unlike SiO2 did not cause liberation of the collagen synthesis-stimulating factor. Fractionation of the medium by gel filtration chromatography showed the SiO2-pretreatment to have caused a very significant decrease in the aggregation state of RNase. The fraction from gel filtration chromatography that contained the SiO2-liberated factor stimulating collagen synthesis also contained the disaggregated RNase. There was no RNase-activity in the control sample. A homogenous protein (mol. wt. 14,300) was isolated with repeated gel filtrations from the medium of silica-treated macrophages. It increased the incorporation of 3H proline and 3H thymidine into cultured granuloma cells."}
{"id": "PMID:225925", "title": "Effect of prostaglandins E1 and F2 alpha on neuromuscular transmission in the frog sartorius muscle.", "content": "End plate potentials (e.p.p.s.) and miniature end plate potentials (m.e.p.p.s.) were recorded intracellularly at the neuromuscular junction of the frog sartorius muscle. Addition of as little as 8.5 x10(-8)M PGE1 reduced the mean m.e.p.p. frequency. The mean amplitude of m.e.p.p.s was not changed, the mean amplitude of the e.p.p.s and the quantum content of the transmitter released by a nerve impulse was slightly reduced. A decrease in mean m.e.p.p. frequency was also seen in response to the administration of 8.5 x 10(-8)M PG2 alpha. The mean amplitude of e.p.p.s and m.e.p.p.s and the quantum content remained unchanged. The possible presynaptic mode of action of PGs in the preparation of discussed.", "contents": "Effect of prostaglandins E1 and F2 alpha on neuromuscular transmission in the frog sartorius muscle. End plate potentials (e.p.p.s.) and miniature end plate potentials (m.e.p.p.s.) were recorded intracellularly at the neuromuscular junction of the frog sartorius muscle. Addition of as little as 8.5 x10(-8)M PGE1 reduced the mean m.e.p.p. frequency. The mean amplitude of m.e.p.p.s was not changed, the mean amplitude of the e.p.p.s and the quantum content of the transmitter released by a nerve impulse was slightly reduced. A decrease in mean m.e.p.p. frequency was also seen in response to the administration of 8.5 x 10(-8)M PG2 alpha. The mean amplitude of e.p.p.s and m.e.p.p.s and the quantum content remained unchanged. The possible presynaptic mode of action of PGs in the preparation of discussed."}
{"id": "PMID:225928", "title": "Angiotensin-converting enzyme in sarcoidosis.", "content": "Using a spectrophotometric assay with L-hippuryl-L-histidyl-L-leucine as substrate, s-angiotensin-converting enzyme (SACE) was determined in 85 sarcoidosis patients, 116 healthy controls and 150 patients with various non-sarcoid diseases. The controls showed no sex or age variation and had SACE levels of 24.4 +/- 6.2 U/ml (mean +/- 1 S.D.), giving a normal range (mean +/- 2 S.D.) of 12.0-36.8 U/ml. In contrast, the sarcoidosis patients had SACE values of 38.4 +/- 14.4 U/ml, with the highest values in cases with active sarcoidosis and duration of disease longer than two years (49.0 +/- 12.7 U/ml). A total of 41% of the sarcoidosis patients had elevated SACE, in the chronic active group 85%. Patients with renal failure, Hodgkin's disease and other malignant lymphoma had low SACE, whereas patients with lung cancer and tuberculosis had normal SACE values. Among 266 patients with non-sarcoid diseases and healthy controls, only two had slightly elevated SACE, but so far we have not found SACE above 40 U/ml in other than sarcoidosis patients. An elevated SACE is rather specific in sarcoidosis and seems to be a useful supplement to existing diagnostic measures.", "contents": "Angiotensin-converting enzyme in sarcoidosis. Using a spectrophotometric assay with L-hippuryl-L-histidyl-L-leucine as substrate, s-angiotensin-converting enzyme (SACE) was determined in 85 sarcoidosis patients, 116 healthy controls and 150 patients with various non-sarcoid diseases. The controls showed no sex or age variation and had SACE levels of 24.4 +/- 6.2 U/ml (mean +/- 1 S.D.), giving a normal range (mean +/- 2 S.D.) of 12.0-36.8 U/ml. In contrast, the sarcoidosis patients had SACE values of 38.4 +/- 14.4 U/ml, with the highest values in cases with active sarcoidosis and duration of disease longer than two years (49.0 +/- 12.7 U/ml). A total of 41% of the sarcoidosis patients had elevated SACE, in the chronic active group 85%. Patients with renal failure, Hodgkin's disease and other malignant lymphoma had low SACE, whereas patients with lung cancer and tuberculosis had normal SACE values. Among 266 patients with non-sarcoid diseases and healthy controls, only two had slightly elevated SACE, but so far we have not found SACE above 40 U/ml in other than sarcoidosis patients. An elevated SACE is rather specific in sarcoidosis and seems to be a useful supplement to existing diagnostic measures."}
{"id": "PMID:225929", "title": "Relationship between biochemical and clinical features in an English Anderson-Fabry family.", "content": "The relationship between biochemical parameters and clinical symptoms in angiokeratoma corporis diffusum universale (Anderson-Fabry's disease) has been studied in an extensive English family. The biochemical parameters measured were alpha-galactosidase activity in urine and in single hair roots and the urinary glycosphingolipid excretion per 24 h. The clinical symptoms evaluated included the occurrence of pain, the prevalence of skin lesions, an abnormal ECG, cornea verticillata and other features. Nine male patients and 13 female carriers were studied. No correlation between biochemical parameters and the severity of the clinical symptoms could be found either in the hemizygotes or in the heterozygotes. The urinary alpha-galactosidase activity in all the heterozygotes lay within the normal range. All the obligate heterozygotes (mothers and daughters of hemizygotes) could be detected by analysis of hair roots. Additional heterozygotes were recognized on the basis of clinical symptoms and hair root analysis.", "contents": "Relationship between biochemical and clinical features in an English Anderson-Fabry family. The relationship between biochemical parameters and clinical symptoms in angiokeratoma corporis diffusum universale (Anderson-Fabry's disease) has been studied in an extensive English family. The biochemical parameters measured were alpha-galactosidase activity in urine and in single hair roots and the urinary glycosphingolipid excretion per 24 h. The clinical symptoms evaluated included the occurrence of pain, the prevalence of skin lesions, an abnormal ECG, cornea verticillata and other features. Nine male patients and 13 female carriers were studied. No correlation between biochemical parameters and the severity of the clinical symptoms could be found either in the hemizygotes or in the heterozygotes. The urinary alpha-galactosidase activity in all the heterozygotes lay within the normal range. All the obligate heterozygotes (mothers and daughters of hemizygotes) could be detected by analysis of hair roots. Additional heterozygotes were recognized on the basis of clinical symptoms and hair root analysis."}
{"id": "PMID:225930", "title": "Interaction of human lymphocytes and viruses in vitro.", "content": "Interaction between phytohaemagglutinin (PHA) stimulated human lymphocytes and two DNA viruses (adenovirus type 5 and herpes simplex virus type 1) considered to be closely connected with lymphoid tissues has been studied. The fate of the same viruses was investigated also in non-stimulated separated lymphocytes for comparative purposes. To elicit this interaction infectivity titrations, immunofluorescent technique and electron microscopy were used. The production of viral antigens was investigated by complement fixation. It has been shown that in PHA-stimulated lymphocytes from peripheral blood of healthy donors adenovirus type 5 is capable to replicate in its infectious form. Prolongation of the interval between stimulation and infection of cells significantly influenced the dynamics of replication. Non-stimulated lymphocytes produced antigens but no infectious particles.", "contents": "Interaction of human lymphocytes and viruses in vitro. Interaction between phytohaemagglutinin (PHA) stimulated human lymphocytes and two DNA viruses (adenovirus type 5 and herpes simplex virus type 1) considered to be closely connected with lymphoid tissues has been studied. The fate of the same viruses was investigated also in non-stimulated separated lymphocytes for comparative purposes. To elicit this interaction infectivity titrations, immunofluorescent technique and electron microscopy were used. The production of viral antigens was investigated by complement fixation. It has been shown that in PHA-stimulated lymphocytes from peripheral blood of healthy donors adenovirus type 5 is capable to replicate in its infectious form. Prolongation of the interval between stimulation and infection of cells significantly influenced the dynamics of replication. Non-stimulated lymphocytes produced antigens but no infectious particles."}
{"id": "PMID:225931", "title": "Detection of antibodies to cytomegalovirus, herpes simplex virus and rubellavirus with the micro-enzyme immunoassay.", "content": "Serum samples of pregnant women (200), non-pregnant women (100) and children (36) were tested for the presence of antibodies to cytomegalovirus (CMV), herpes simplex virus (HSV) and rubellavirus with the micro-enzyme immunoassay (micro-EAI), the indirect immunofluorescence antibody (IFA) technique and the haemagglutination-inhibition (HI) test. Micro-EIA gave the highest positivity rate: 78% for CMV, 86% for HSV and 85% for rubellavirus compared to 67% (CMV) and 84% (HSV) of the IFA technique and 79% (rubellavirus) of the HI test, respectively. Among IFA and HI positive sera the occurrence of micro-EIA negative ones was 6% for CMV, 4% for HSV and 9% for rubellavirus. It is concluded that the introduction of micro-EIA will improve the diagnostic and screening work of virus laboratories.", "contents": "Detection of antibodies to cytomegalovirus, herpes simplex virus and rubellavirus with the micro-enzyme immunoassay. Serum samples of pregnant women (200), non-pregnant women (100) and children (36) were tested for the presence of antibodies to cytomegalovirus (CMV), herpes simplex virus (HSV) and rubellavirus with the micro-enzyme immunoassay (micro-EAI), the indirect immunofluorescence antibody (IFA) technique and the haemagglutination-inhibition (HI) test. Micro-EIA gave the highest positivity rate: 78% for CMV, 86% for HSV and 85% for rubellavirus compared to 67% (CMV) and 84% (HSV) of the IFA technique and 79% (rubellavirus) of the HI test, respectively. Among IFA and HI positive sera the occurrence of micro-EIA negative ones was 6% for CMV, 4% for HSV and 9% for rubellavirus. It is concluded that the introduction of micro-EIA will improve the diagnostic and screening work of virus laboratories."}
{"id": "PMID:225932", "title": "Cells containing Epstein--Barr nuclear antigen (EBNA) in peripheral blood.", "content": "The anti-complement immunofluorescence (ACIF) method was used to demonstrate EBNA in B lymphocytes separated from the peripheral blood of patients with infectious mononucleosis (IM) or other diseases. In the acute phase of IM of Epstein-Barr virus (EBV) origin, 0.5--1% of the B lymphocytes proved to be positive in 6 of the 8 patients tested. In two of the positive cases the test was repeated 20 and 26 days, respectively, after clinical symptoms had appeared; the result was negative in both cases. No EBNA-positive cells were found in the peripheral blood of 17 patients with Hodgkin disease, 3 with systemic lupus erythematosus and 2 with lymphosarcoma. It is supposed that EBNA-positive cells appear in detectable amount exclusively in the acute phase of EBV infection.", "contents": "Cells containing Epstein--Barr nuclear antigen (EBNA) in peripheral blood. The anti-complement immunofluorescence (ACIF) method was used to demonstrate EBNA in B lymphocytes separated from the peripheral blood of patients with infectious mononucleosis (IM) or other diseases. In the acute phase of IM of Epstein-Barr virus (EBV) origin, 0.5--1% of the B lymphocytes proved to be positive in 6 of the 8 patients tested. In two of the positive cases the test was repeated 20 and 26 days, respectively, after clinical symptoms had appeared; the result was negative in both cases. No EBNA-positive cells were found in the peripheral blood of 17 patients with Hodgkin disease, 3 with systemic lupus erythematosus and 2 with lymphosarcoma. It is supposed that EBNA-positive cells appear in detectable amount exclusively in the acute phase of EBV infection."}
{"id": "PMID:225933", "title": "Interaction of peripheral and cerebellar inputs to red nucleus neurons.", "content": "In chloralose anesthetized cats responses of red nucleus neurons to cerebellar cortical or peripheral stimulation are described. Interactions between cerebellar (conditioning) and peripheral (test) stimulations were studied at various interstimulus intervals. Peripheral stimulation alone typically evoked a complex response consisting of an early (15 ms latency) burst, a period of depression of activity (inhibition, lasting up to 300 ms) and a late, long-lasting (on an average 300 ms) excitation. Cerebellar cortical stimulation resulted in a similar pattern of response; but it was composed predominantly of only two phases, an initial inhibition followed by a prolonged late discharge. With conditioning- testing intervals in a range of 10-150 ms, depending on the cell, there was a conspicuous depression of the sh0i.t-latency test excitation, followed by a prominent potentiation of this component. An occlusion of the inhibitory or late excitatory responses occurred when conditioning-testing stimuli were applied with an interval shorter than 0.5 s. It is suggested that the early excitation and the subsequent late components are generated in the red nucleus by independent mechanisms. The initial depression of the early test response is explained as an effect of Purkinje cell inhibition, and the later potentiation as a result of temporary blockage of the cerebellar cortex to afferent input.", "contents": "Interaction of peripheral and cerebellar inputs to red nucleus neurons. In chloralose anesthetized cats responses of red nucleus neurons to cerebellar cortical or peripheral stimulation are described. Interactions between cerebellar (conditioning) and peripheral (test) stimulations were studied at various interstimulus intervals. Peripheral stimulation alone typically evoked a complex response consisting of an early (15 ms latency) burst, a period of depression of activity (inhibition, lasting up to 300 ms) and a late, long-lasting (on an average 300 ms) excitation. Cerebellar cortical stimulation resulted in a similar pattern of response; but it was composed predominantly of only two phases, an initial inhibition followed by a prolonged late discharge. With conditioning- testing intervals in a range of 10-150 ms, depending on the cell, there was a conspicuous depression of the sh0i.t-latency test excitation, followed by a prominent potentiation of this component. An occlusion of the inhibitory or late excitatory responses occurred when conditioning-testing stimuli were applied with an interval shorter than 0.5 s. It is suggested that the early excitation and the subsequent late components are generated in the red nucleus by independent mechanisms. The initial depression of the early test response is explained as an effect of Purkinje cell inhibition, and the later potentiation as a result of temporary blockage of the cerebellar cortex to afferent input."}
{"id": "PMID:225938", "title": "Reversibility of changes in evoked spinal response following graded spinal cord compression.", "content": "The spinal evoked response obtained in cats at a site immediately rostral to the site of a graded spinal cord compression is described. They usually show an earlier decrease in amplitude than cortical SEP's and the appearance of a particular positive potential. The degree of reversibility after decompression is variable and is not correlated with histological damage.", "contents": "Reversibility of changes in evoked spinal response following graded spinal cord compression. The spinal evoked response obtained in cats at a site immediately rostral to the site of a graded spinal cord compression is described. They usually show an earlier decrease in amplitude than cortical SEP's and the appearance of a particular positive potential. The degree of reversibility after decompression is variable and is not correlated with histological damage."}
{"id": "PMID:225940", "title": "Pathological actin in vestibular hair cells of the waltzing guinea pig.", "content": "Vestibular type 1 hair cells in the waltzing guinea pig contain needle-shaped inclusion bodies which grow in an uncontrolled fashion associated with the destruction of the cell. The needles are shown to be composed by filaments of actin, a protein identified in the electron microscope by its ability to bind subfragment 1 of myosin. Whereas actin filaments in stereocilia are oriented down towards the cell body, filaments in the needles point up towards the cuticular plate. The hereditary lesion appears to be associated with a defective control of polymerization of actin into filaments.", "contents": "Pathological actin in vestibular hair cells of the waltzing guinea pig. Vestibular type 1 hair cells in the waltzing guinea pig contain needle-shaped inclusion bodies which grow in an uncontrolled fashion associated with the destruction of the cell. The needles are shown to be composed by filaments of actin, a protein identified in the electron microscope by its ability to bind subfragment 1 of myosin. Whereas actin filaments in stereocilia are oriented down towards the cell body, filaments in the needles point up towards the cuticular plate. The hereditary lesion appears to be associated with a defective control of polymerization of actin into filaments."}
{"id": "PMID:225945", "title": "Therapeutic embolization of juvenile angiofibroma.", "content": "Therapeutic embolization of juvenile angiofibromas was performed in 15 boys, aged 12--18 years, 11 of whom subsequently underwent surgery. Intraoperative blood loss was reduced from an average of 2,400 ml in nonembolized patients to 800 ml after embolization. Angiography is of value to confirm the diagnosis prior to excision and to delineate the extent of the tumor. Embolization may be performed at the same sitting as a presurgical adjunct or possibly as a definitive or palliative therapeutic method. The embolization procedure is discussed in detail, emphasizing techniques and potential hazards of such procedures.", "contents": "Therapeutic embolization of juvenile angiofibroma. Therapeutic embolization of juvenile angiofibromas was performed in 15 boys, aged 12--18 years, 11 of whom subsequently underwent surgery. Intraoperative blood loss was reduced from an average of 2,400 ml in nonembolized patients to 800 ml after embolization. Angiography is of value to confirm the diagnosis prior to excision and to delineate the extent of the tumor. Embolization may be performed at the same sitting as a presurgical adjunct or possibly as a definitive or palliative therapeutic method. The embolization procedure is discussed in detail, emphasizing techniques and potential hazards of such procedures."}
{"id": "PMID:225946", "title": "The use of sand substitution to solve the free silica problem in foundry atmospheres.", "content": "Field tests were carried out to compare the air quailty in a gray iron foundry before and after changing the molding material from the standard silica based sand to the mineral olivine. Olivine is a magnesium iron silicate (Mg, Fe) SiO4 which occurs in nature and contains little or no free silica. Data were collected using standard OSHA approved methods to determine the total dust and the respirable limit for the alpha-quartz particle loading levels. Additional samples were taken using a cascade impactor and filter tape samplers. The foundry was surveyed once before the substitution of olivine and three times after the changeover. The study demonstrates that the partial substitution of olivine can reduce the concentration of free silica to acceptable health levels. However, contamination from processes using silica sand must be controlled.", "contents": "The use of sand substitution to solve the free silica problem in foundry atmospheres. Field tests were carried out to compare the air quailty in a gray iron foundry before and after changing the molding material from the standard silica based sand to the mineral olivine. Olivine is a magnesium iron silicate (Mg, Fe) SiO4 which occurs in nature and contains little or no free silica. Data were collected using standard OSHA approved methods to determine the total dust and the respirable limit for the alpha-quartz particle loading levels. Additional samples were taken using a cascade impactor and filter tape samplers. The foundry was surveyed once before the substitution of olivine and three times after the changeover. The study demonstrates that the partial substitution of olivine can reduce the concentration of free silica to acceptable health levels. However, contamination from processes using silica sand must be controlled."}
{"id": "PMID:225947", "title": "Temporal relation between onset of cell anoxia and ischemic contractile failure. Myocardial ischemia and left ventricular failure in the isolated, perfused rabbit heart.", "content": "Contractile dysfunction is characteristic of the acutely ischemic myocardium. This study was undertaken to assess the temporal relations between the onset of cell anoxia and ischemic contractile failure in isolated, isovolumetric contracting rabbit hearts. High speed epicardial fluorescence photography using reduced nicotinamide adenosine nucleotide (NADH) was used to identify areas of cell anoxia. The onset of ischemia was correlated with deterioration of pressure generation over the course of sequential 60 second coronary arterial occlusions. In the isovolumetric contracting rabbit heart, areas of ischemia were detected 2 seconds after coronary occlusion. Significant reduction in peak systolic pressure occurred at 6 seconds of ischemic time and pressure continued to decrease throughout the 60 second period of coronary occlusion. NADH accumulation indicates imbalance of myocardial oxygen supply and demand and the cessation of oxygen utilization by the mitochondria. The results of this study indicate that ischemia is detectable within 1 to 2 seconds after coronary occlusion and that ischemic ventricular dysfunction occurs several seconds thereafter. Myocardial oxygen reserve is negligible.", "contents": "Temporal relation between onset of cell anoxia and ischemic contractile failure. Myocardial ischemia and left ventricular failure in the isolated, perfused rabbit heart. Contractile dysfunction is characteristic of the acutely ischemic myocardium. This study was undertaken to assess the temporal relations between the onset of cell anoxia and ischemic contractile failure in isolated, isovolumetric contracting rabbit hearts. High speed epicardial fluorescence photography using reduced nicotinamide adenosine nucleotide (NADH) was used to identify areas of cell anoxia. The onset of ischemia was correlated with deterioration of pressure generation over the course of sequential 60 second coronary arterial occlusions. In the isovolumetric contracting rabbit heart, areas of ischemia were detected 2 seconds after coronary occlusion. Significant reduction in peak systolic pressure occurred at 6 seconds of ischemic time and pressure continued to decrease throughout the 60 second period of coronary occlusion. NADH accumulation indicates imbalance of myocardial oxygen supply and demand and the cessation of oxygen utilization by the mitochondria. The results of this study indicate that ischemia is detectable within 1 to 2 seconds after coronary occlusion and that ischemic ventricular dysfunction occurs several seconds thereafter. Myocardial oxygen reserve is negligible."}
{"id": "PMID:225948", "title": "Unexpected decrease in plasma high density lipoprotein cholesterol with weight loss.", "content": "High density lipoprotein (HDL) cholesterol is inversely related to coronary heart disease prevalence. Despite the fact that obese patients have lower plasma HDL-cholesterol concentrations, there are few prospective studies on the effect of weight loss on HDL-cholesterol. Consequently, plasma lipoprotein levels were measured in 15 obese females before and after a 10 week weight loss program. Mean weight loss was 8.6 +/- 3.9 kg (P less than 0.001). Total plasma cholesterol and low density lipoprotein-cholesterol did not change significantly. Plasma triglyceride levels decreased (P less than 0.05) as did HDL-cholesterol (P less than 0.02). A subgroup of 11 of the subjects had repeat lipid measurements 8 months after the start of treatment. Mean weight loss at this time was 12.8 +/- 0.8 kg (P less than 0.01). No subject had returned to her pretreatment weight but mean weight loss was not significantly different from the 10 week value. At 8 months all lipid values, including HDL-cholesterol, had returned to their pretreatment value. By multiple regression analysis HDL-cholesterol decreased with increasing relative weight but also decreased with increasing rate of weight loss. These results suggest that negative caloric balance produces a decrease in HDL-cholesterol that in prospective studies may obscure the inverse relationship between HDL-cholesterol and indices of obesity.", "contents": "Unexpected decrease in plasma high density lipoprotein cholesterol with weight loss. High density lipoprotein (HDL) cholesterol is inversely related to coronary heart disease prevalence. Despite the fact that obese patients have lower plasma HDL-cholesterol concentrations, there are few prospective studies on the effect of weight loss on HDL-cholesterol. Consequently, plasma lipoprotein levels were measured in 15 obese females before and after a 10 week weight loss program. Mean weight loss was 8.6 +/- 3.9 kg (P less than 0.001). Total plasma cholesterol and low density lipoprotein-cholesterol did not change significantly. Plasma triglyceride levels decreased (P less than 0.05) as did HDL-cholesterol (P less than 0.02). A subgroup of 11 of the subjects had repeat lipid measurements 8 months after the start of treatment. Mean weight loss at this time was 12.8 +/- 0.8 kg (P less than 0.01). No subject had returned to her pretreatment weight but mean weight loss was not significantly different from the 10 week value. At 8 months all lipid values, including HDL-cholesterol, had returned to their pretreatment value. By multiple regression analysis HDL-cholesterol decreased with increasing relative weight but also decreased with increasing rate of weight loss. These results suggest that negative caloric balance produces a decrease in HDL-cholesterol that in prospective studies may obscure the inverse relationship between HDL-cholesterol and indices of obesity."}
{"id": "PMID:225949", "title": "Intralipid clearance and lipoprotein pattern in men with advanced alcoholic liver cirrhosis.", "content": "Twelve male patients with advanced alcoholic cirrhosis of the liver were found to have markedly low serum lipid and lipoprotein concentrations. Serum triglyceride and cholesterol concentrations were about 50% of matched control values. The very low density lipoprotein-triglyceride concentration was only one-third of control values and the cholesterol concentrations in very low density and low density lipoproteins were far below control values. The mean high density lipoprotein cholesterol concentration was not significantly decreased, but in three of 12 patients extremely low values were found. These findings may reflect a failure of lipoprotein synthesis secondary to a bad nutritional state and metabolic disturbances in this advanced stage of liver cirrhosis. By means of the intravenous fat tolerance test with Intralipid it could be shown that substantial amounts of triglycerides could be cleared from the plasma in these patients. However, studies on the long-term Intralipid clearance capacity have to be performed before any general recommendations about the inclusion of fat emulsions in parenteral nutrition of these patients can be made.", "contents": "Intralipid clearance and lipoprotein pattern in men with advanced alcoholic liver cirrhosis. Twelve male patients with advanced alcoholic cirrhosis of the liver were found to have markedly low serum lipid and lipoprotein concentrations. Serum triglyceride and cholesterol concentrations were about 50% of matched control values. The very low density lipoprotein-triglyceride concentration was only one-third of control values and the cholesterol concentrations in very low density and low density lipoproteins were far below control values. The mean high density lipoprotein cholesterol concentration was not significantly decreased, but in three of 12 patients extremely low values were found. These findings may reflect a failure of lipoprotein synthesis secondary to a bad nutritional state and metabolic disturbances in this advanced stage of liver cirrhosis. By means of the intravenous fat tolerance test with Intralipid it could be shown that substantial amounts of triglycerides could be cleared from the plasma in these patients. However, studies on the long-term Intralipid clearance capacity have to be performed before any general recommendations about the inclusion of fat emulsions in parenteral nutrition of these patients can be made."}
{"id": "PMID:225950", "title": "Nuclear medicine and cancer research in the People's Republic of China.", "content": "This article reports the experience of the author's recent visit to China where he witnessed nuclear medicine facilities. Among other things, the author observes that most imaging equipment and radionuclides are made in China and that many good textbooks of nuclear medicine are available in Chinese. Precautions on radiation safety are very much stressed. Chinese medicinal plants are always added in order to improve the therapeutic effects of classical chemotherapeutic agents or to lessen their possible side effects. Their scientific value cannot be evaluated, nor can it be for the \"anti-cancer pills\" that are sold freely. The author encourages studies of different patterns of cancer problems in different geographic localities, as he gave indications for a few geographic areas.", "contents": "Nuclear medicine and cancer research in the People's Republic of China. This article reports the experience of the author's recent visit to China where he witnessed nuclear medicine facilities. Among other things, the author observes that most imaging equipment and radionuclides are made in China and that many good textbooks of nuclear medicine are available in Chinese. Precautions on radiation safety are very much stressed. Chinese medicinal plants are always added in order to improve the therapeutic effects of classical chemotherapeutic agents or to lessen their possible side effects. Their scientific value cannot be evaluated, nor can it be for the \"anti-cancer pills\" that are sold freely. The author encourages studies of different patterns of cancer problems in different geographic localities, as he gave indications for a few geographic areas."}
{"id": "PMID:225951", "title": "SV40 T-antigen expression in cultured fibroblasts from patients with Down syndrome and their parents.", "content": "Expression of simian papovavirus 40 (SV40) T-antigen following in vitro infection was studied in skin fibroblasts from patients with Down syndrome (DS) and their parents to determine whether the increased susceptibility to SV40 infection reflected the cytogenetic defect or the leukemia risk associated with this syndrome. As a group, fibroblasts from patients with DS showed elevated T-antigen expression 72 hrs after infection compared to that of a healthy control population. However, among 24 patients tested, the cell lines of only 11 showed statistically significant increases in T-antigen expression. A cell line from a patient with concurrent DS and acute myelogenous leukemia had a normal value. T-antigen expression did not correlate with the percentage of cells trisomic for chromosome 21 in 18 cell lines examined or with the number of copies of this chromosome in disomic and trisomic cell strains cloned from three mosaic patients.Collectively, cell lines from parents of trisomy 21 patients also showed increased susceptibility to SV40 infection; however, in five families tested, a consistent pattern of genetic transmission of elevated T-antigen expression from parent to offspring was not observed. Q-banding of cell lines in one family showed that elevated T-antigen expression is not a marker of parental nondisjunction. Variation in susceptibility to human interferon, an antiviral agent, did not account for variation in T-antigen levels among these cell lines. Thus, the abnormalities of T-antigen expression in DS appear independent of the hyperdiploid state and are not a sensitive indicator of cancer risk.", "contents": "SV40 T-antigen expression in cultured fibroblasts from patients with Down syndrome and their parents. Expression of simian papovavirus 40 (SV40) T-antigen following in vitro infection was studied in skin fibroblasts from patients with Down syndrome (DS) and their parents to determine whether the increased susceptibility to SV40 infection reflected the cytogenetic defect or the leukemia risk associated with this syndrome. As a group, fibroblasts from patients with DS showed elevated T-antigen expression 72 hrs after infection compared to that of a healthy control population. However, among 24 patients tested, the cell lines of only 11 showed statistically significant increases in T-antigen expression. A cell line from a patient with concurrent DS and acute myelogenous leukemia had a normal value. T-antigen expression did not correlate with the percentage of cells trisomic for chromosome 21 in 18 cell lines examined or with the number of copies of this chromosome in disomic and trisomic cell strains cloned from three mosaic patients.Collectively, cell lines from parents of trisomy 21 patients also showed increased susceptibility to SV40 infection; however, in five families tested, a consistent pattern of genetic transmission of elevated T-antigen expression from parent to offspring was not observed. Q-banding of cell lines in one family showed that elevated T-antigen expression is not a marker of parental nondisjunction. Variation in susceptibility to human interferon, an antiviral agent, did not account for variation in T-antigen levels among these cell lines. Thus, the abnormalities of T-antigen expression in DS appear independent of the hyperdiploid state and are not a sensitive indicator of cancer risk."}
{"id": "PMID:225952", "title": "Brief clinical observations: the Neu-Laxova syndrome--a distinct entity.", "content": "We report a stillborn girl with a complex syndrome of microcephaly, lissencephaly, severe subcutaneous edema, atrophic muscles, camptodactyly, syndactyly of toes and fingers, hypoplastic genitalia, and numerous structural changes of the brain and eyes. Similar cases have been reported by Neu et al [1], Laxova et al [2] and Povysilova et al [3]. The above-mentioned syndrome complex is a distinct genetic syndrome, for which we propose the eponym \"the Neu-Laxova syndrome.\" Affected patients resemble each other strikingly and there is usually no doubt about the diagnosis. The Neu-Laxova syndrome is apparently transmitted as an autosomal recessive trait.", "contents": "Brief clinical observations: the Neu-Laxova syndrome--a distinct entity. We report a stillborn girl with a complex syndrome of microcephaly, lissencephaly, severe subcutaneous edema, atrophic muscles, camptodactyly, syndactyly of toes and fingers, hypoplastic genitalia, and numerous structural changes of the brain and eyes. Similar cases have been reported by Neu et al [1], Laxova et al [2] and Povysilova et al [3]. The above-mentioned syndrome complex is a distinct genetic syndrome, for which we propose the eponym \"the Neu-Laxova syndrome.\" Affected patients resemble each other strikingly and there is usually no doubt about the diagnosis. The Neu-Laxova syndrome is apparently transmitted as an autosomal recessive trait."}
{"id": "PMID:225953", "title": "The utility of a rapid assay for human chorionic gonadotropin in the management of trophoblastic disease.", "content": "The diagnosis and treatment of trophoblastic disease depend upon the reliable measurement of human chorionic gonadotropin (hCG) in serum or urine. The double-antibody hCG beta-subunit assay for serum hCG combines great sensitivity, specificity, and precision but requires 36 hours to yield results. This investigation sought to increase the efficiency and total assay volume capabilities of our laboratory through the development of rapid hCG assay to augment the slower beta-subunit system. Two separate rapid hCG assays were examined--a double-antibody radioimmunoassay and a radioreceptor assay. The double-antibody assay took 5 hours to complete, while the radioreceptor assay could be completed with 3 1/2 hours. One hundred serum samples from patients with trophoblastic disease were assayed for hCG in the beta-subunit radioimmunoassay and in both rapid assay systems. No differences in results produced by the rapid double-antibody and the hCG beta-subunit assays were noted; however, results from the radioreceptor assay were significantly different (p less than 0.05) from those obtained in the beta-subunit system.", "contents": "The utility of a rapid assay for human chorionic gonadotropin in the management of trophoblastic disease. The diagnosis and treatment of trophoblastic disease depend upon the reliable measurement of human chorionic gonadotropin (hCG) in serum or urine. The double-antibody hCG beta-subunit assay for serum hCG combines great sensitivity, specificity, and precision but requires 36 hours to yield results. This investigation sought to increase the efficiency and total assay volume capabilities of our laboratory through the development of rapid hCG assay to augment the slower beta-subunit system. Two separate rapid hCG assays were examined--a double-antibody radioimmunoassay and a radioreceptor assay. The double-antibody assay took 5 hours to complete, while the radioreceptor assay could be completed with 3 1/2 hours. One hundred serum samples from patients with trophoblastic disease were assayed for hCG in the beta-subunit radioimmunoassay and in both rapid assay systems. No differences in results produced by the rapid double-antibody and the hCG beta-subunit assays were noted; however, results from the radioreceptor assay were significantly different (p less than 0.05) from those obtained in the beta-subunit system."}
{"id": "PMID:225955", "title": "Visuospatial dysgnosia.", "content": "Spatial dysgnosia may occur in patients with various forms of brain disease, including tumors, vascular accidents, Alzheimer's disease, multiple sclerosis, and developmental aberrations. Patients with lesion in the nondominant hemisphere, particularly at the junction of the occipito-temporoparietal regions, may manifest predominantly visuospatial dysgnosia--a loss of the sense of \"whereness\" in the relation of himself to his environment and in the relation of objects to each other. Visuospatial disturbances caused by lesions in the dominant hemisphere may be masked by other gnostic symptoms. Patients with more extensive lesions, especially those involving similar areas in both hemispheres, may also exhibit other cognitive disturbances associated with vision.", "contents": "Visuospatial dysgnosia. Spatial dysgnosia may occur in patients with various forms of brain disease, including tumors, vascular accidents, Alzheimer's disease, multiple sclerosis, and developmental aberrations. Patients with lesion in the nondominant hemisphere, particularly at the junction of the occipito-temporoparietal regions, may manifest predominantly visuospatial dysgnosia--a loss of the sense of \"whereness\" in the relation of himself to his environment and in the relation of objects to each other. Visuospatial disturbances caused by lesions in the dominant hemisphere may be masked by other gnostic symptoms. Patients with more extensive lesions, especially those involving similar areas in both hemispheres, may also exhibit other cognitive disturbances associated with vision."}
{"id": "PMID:225956", "title": "Temporal firing sequences of antagonistic muscles.", "content": "The purpose of this study was to assess the relationship between paired agonist/antagonist muscle firing times and accompanying time to peak EMG amplitudes with a 75 degree ballistic right forearm flexion task during experimental conditions of A) no external limb resistance, B) 3.1 Kg., and C) 9.8 Kg. of premovement limb resistance. In addition, total reaction time and movement time values were compared relative to the experimental conditions. Twelve male subjects practiced the flexion task for three days until criterion measures stabilized. Following five control measures on each of the next two days, 10 trials each of conditions A, B, C appearing in random order were administered. Results indicated that as external limb resistance increased (from A to B to C), movement time decreased by 30 msec., total reaction time increased by 52 msec., while biceps latency remained unchanged. There were significant (p less than0.05) increases in triceps latency, biceps and triceps time to peak EMG amplitude only with respect to the greatest external resistance (condition C). It is speculated that coordination may be defined in terms of the temporal firing sequences within an agonist/antagonist muscle group.", "contents": "Temporal firing sequences of antagonistic muscles. The purpose of this study was to assess the relationship between paired agonist/antagonist muscle firing times and accompanying time to peak EMG amplitudes with a 75 degree ballistic right forearm flexion task during experimental conditions of A) no external limb resistance, B) 3.1 Kg., and C) 9.8 Kg. of premovement limb resistance. In addition, total reaction time and movement time values were compared relative to the experimental conditions. Twelve male subjects practiced the flexion task for three days until criterion measures stabilized. Following five control measures on each of the next two days, 10 trials each of conditions A, B, C appearing in random order were administered. Results indicated that as external limb resistance increased (from A to B to C), movement time decreased by 30 msec., total reaction time increased by 52 msec., while biceps latency remained unchanged. There were significant (p less than0.05) increases in triceps latency, biceps and triceps time to peak EMG amplitude only with respect to the greatest external resistance (condition C). It is speculated that coordination may be defined in terms of the temporal firing sequences within an agonist/antagonist muscle group."}
{"id": "PMID:225957", "title": "Continuity of care in the delivery of mental health services.", "content": "The authors report on the help-seeking experiences of people referred to community settings for aftercare on discharge from a state mental hospital in western Massachusetts. They present results that bear on three questions relevant to public policy issues in the mental health field: 1) the proportion of patients who comply with referrals to aftercare agencies, 2) the social and psychological characteristics of patients who comply with these referrals, and 3) the impact of receiving aftercare on the probability of rehospitalization.", "contents": "Continuity of care in the delivery of mental health services. The authors report on the help-seeking experiences of people referred to community settings for aftercare on discharge from a state mental hospital in western Massachusetts. They present results that bear on three questions relevant to public policy issues in the mental health field: 1) the proportion of patients who comply with referrals to aftercare agencies, 2) the social and psychological characteristics of patients who comply with these referrals, and 3) the impact of receiving aftercare on the probability of rehospitalization."}
{"id": "PMID:225958", "title": "Health consequences of the snow disaster in Massachusetts, February 6, 1978.", "content": "On February 6, 1978, the largest New England blizzard of the century struck eastern Massachusetts. On request, four days later, the Center for Disease Control provided epidemiologic assistance. On-site disaster assistance provided decision-makers with immediate health surveillance information useful in helping the area return to normal. No outbreaks of infectious diseases and no significant increase in the number of deaths were observed in the week following the blizzard. Some of the deaths which occurred immediately after the blizzard might have been prevented if traffic had been banned earlier.", "contents": "Health consequences of the snow disaster in Massachusetts, February 6, 1978. On February 6, 1978, the largest New England blizzard of the century struck eastern Massachusetts. On request, four days later, the Center for Disease Control provided epidemiologic assistance. On-site disaster assistance provided decision-makers with immediate health surveillance information useful in helping the area return to normal. No outbreaks of infectious diseases and no significant increase in the number of deaths were observed in the week following the blizzard. Some of the deaths which occurred immediately after the blizzard might have been prevented if traffic had been banned earlier."}
{"id": "PMID:225959", "title": "Antigenic analyses of two axenized strains of Entamoeba histolytica by two-dimensional immunoelectrophoresis.", "content": "Antigens in extracts of two strains of Entamoeba histolytica (HT-31 and HK-9) were studied by two-dimensional immunoelectrophoresis (2D-IEP) and 32 and 20 different antigenic components were detected, respectively. Cross-reactions between heterologous systems showed a large number of shared antigens between the two strains. Extracts were fractionated by Sephadex G-200 chromatography. Of the fractions obtained, fraction II of both strains was found to have the most reactive antigenic components. Precipitin patterns of fraction II from HT-31 and HK-9 with sera from patients showed similar 2D-IEP profiles and suggested that in this fraction antigens common to both strains exist which elicit antibody in individuals with E. histolytica infections.", "contents": "Antigenic analyses of two axenized strains of Entamoeba histolytica by two-dimensional immunoelectrophoresis. Antigens in extracts of two strains of Entamoeba histolytica (HT-31 and HK-9) were studied by two-dimensional immunoelectrophoresis (2D-IEP) and 32 and 20 different antigenic components were detected, respectively. Cross-reactions between heterologous systems showed a large number of shared antigens between the two strains. Extracts were fractionated by Sephadex G-200 chromatography. Of the fractions obtained, fraction II of both strains was found to have the most reactive antigenic components. Precipitin patterns of fraction II from HT-31 and HK-9 with sera from patients showed similar 2D-IEP profiles and suggested that in this fraction antigens common to both strains exist which elicit antibody in individuals with E. histolytica infections."}
{"id": "PMID:225961", "title": "Adenoid cystic carcinoma: factors influencing survival.", "content": "We have reviewed our experience with 264 patients treated for adenoid cystic carcinoma of salivary origin. This study updates a previous report from our hospital and includes all patients treated during a 30 year period who were eligible for a minimum follow-up of 10 years. The tumor arose in minor salivary (mucous) glands in two thirds of the patients; half had received treatment elsewhere, and both sexes were equally represented. Actuarial survival curves and \"cure\" rates calculated by the direct method confirm that clinical staging provides a reliable prognostic guide. We are unable to demonstrate that the microscopic appearance of the tumor exerts a predictable effect on treatment results. Although some patients lived for many years after resection despite local recurrence and distant metastases, prolonged survival was unusual in patients with stage 3 lesions, particularly in those with sinus or submaxillary gland primaries. Based on the site of origin of the tumor and its clinical stage, it is now possible to select which patients with adenoid cystic carcinoma have the most ominous prognosis and perhaps plan a more appropriate operation. More importantly, these data may help focus on the subpopulation at greatest risk, which is vital to the design of any prospective study to assess the value of adjunctive irradiation and chemotherapy.", "contents": "Adenoid cystic carcinoma: factors influencing survival. We have reviewed our experience with 264 patients treated for adenoid cystic carcinoma of salivary origin. This study updates a previous report from our hospital and includes all patients treated during a 30 year period who were eligible for a minimum follow-up of 10 years. The tumor arose in minor salivary (mucous) glands in two thirds of the patients; half had received treatment elsewhere, and both sexes were equally represented. Actuarial survival curves and \"cure\" rates calculated by the direct method confirm that clinical staging provides a reliable prognostic guide. We are unable to demonstrate that the microscopic appearance of the tumor exerts a predictable effect on treatment results. Although some patients lived for many years after resection despite local recurrence and distant metastases, prolonged survival was unusual in patients with stage 3 lesions, particularly in those with sinus or submaxillary gland primaries. Based on the site of origin of the tumor and its clinical stage, it is now possible to select which patients with adenoid cystic carcinoma have the most ominous prognosis and perhaps plan a more appropriate operation. More importantly, these data may help focus on the subpopulation at greatest risk, which is vital to the design of any prospective study to assess the value of adjunctive irradiation and chemotherapy."}
{"id": "PMID:225962", "title": "Granular cell myoblastoma of the head and neck: review of the literature and 10 year experience.", "content": "The literature on granular cell myoblastoma (Abrikossoff's tumor) is reviewed and 16 new cases are presented. The etiology of this tumor remains uncertain, although a neurogenic origin appears likely. Individual tumors are usually small, nodular, and nonulcerating. There appeared to be no predilection for either sex in our series, and most tumors occurred between the third and sixth decades of life. Pseudoepitheliomatous hyperplasia is frequently associated with granular cell myoblastoma, and this combination must be distinguished from squamous cell carcinoma. Wide local excision, the treatment of choice, should be curative, although the incidence of multicentricity may exceed 15%. Thus, despite the usually benign nature of granular cell myoblastoma, its propensity for local invasion, multicentricity, and associated pseudoepitheliomatous hyperplasia should alert surgeons to its potential hazards, to the probability of recurrence if it is only marginally excised, and to the possible later development of similar lesions.", "contents": "Granular cell myoblastoma of the head and neck: review of the literature and 10 year experience. The literature on granular cell myoblastoma (Abrikossoff's tumor) is reviewed and 16 new cases are presented. The etiology of this tumor remains uncertain, although a neurogenic origin appears likely. Individual tumors are usually small, nodular, and nonulcerating. There appeared to be no predilection for either sex in our series, and most tumors occurred between the third and sixth decades of life. Pseudoepitheliomatous hyperplasia is frequently associated with granular cell myoblastoma, and this combination must be distinguished from squamous cell carcinoma. Wide local excision, the treatment of choice, should be curative, although the incidence of multicentricity may exceed 15%. Thus, despite the usually benign nature of granular cell myoblastoma, its propensity for local invasion, multicentricity, and associated pseudoepitheliomatous hyperplasia should alert surgeons to its potential hazards, to the probability of recurrence if it is only marginally excised, and to the possible later development of similar lesions."}
{"id": "PMID:225970", "title": "Chronological versus skeletal age, an evaluation of craniofacial growth.", "content": "Skeletal and chronologic ages of both female and male populations were compared relative to the degree of concurrence between the two age-indices at the various age levels. Maxillary and mandibular cephalometric measurements were similarly compared for both sex groups. Individual's comparisons of facial changes were made relative to their respective chronologic and skeletal ages. The significance of a skeletal vs. chronologic age discrepancy and its relationship to the timing of facial growth was demonstrated. Clinical implications were discussed.", "contents": "Chronological versus skeletal age, an evaluation of craniofacial growth. Skeletal and chronologic ages of both female and male populations were compared relative to the degree of concurrence between the two age-indices at the various age levels. Maxillary and mandibular cephalometric measurements were similarly compared for both sex groups. Individual's comparisons of facial changes were made relative to their respective chronologic and skeletal ages. The significance of a skeletal vs. chronologic age discrepancy and its relationship to the timing of facial growth was demonstrated. Clinical implications were discussed."}
{"id": "PMID:225966", "title": "[Post-operative hyperaldosteronism and related endocrine perturbations (author's transl)].", "content": "Electrolytes disturbances during operative period are believed to be related to an hyperaldosteronism produced by anaesthetic management and surgery. Effects of ethrane anaesthesia and surgery on hydroelectrolytic metabolism and endocrin function were investigated in 11 patients submitted to an abdominal surgery. Plasma and urinary levels of aldosterone were increased (x3) significantly (p less than or equal to 0.001) during operation, then decreased gradually in post-operative period, and return to normal values when Na/K ratio is reversed in urines. Relationship between hyperaldosteronism and other changes in endocrine function are established by determination of following hormones: A.C.T.H., cortisol, plasma renin activity (P.R.A.) catecholamines in plasma and urinary levels of 17-ceto, 17-hydroxysteroids and catecholamines. Ethrane anesthesia give a good neurovegetative stability since plasma catecholamines levels are not affected significatively. Plasma aldosterone level is correlated with urinary aldosterone and plasma renin activity. Plasma A.C.T.H. is much more increased at the operative time and decreases rapidly instead of plasma cortisol which decreases more slowly. Relationship of this hyperaldosteronism with anesthetic management, surgical stress intestinal transit disturbances, other endocrine function changes is discussed.", "contents": "[Post-operative hyperaldosteronism and related endocrine perturbations (author's transl)]. Electrolytes disturbances during operative period are believed to be related to an hyperaldosteronism produced by anaesthetic management and surgery. Effects of ethrane anaesthesia and surgery on hydroelectrolytic metabolism and endocrin function were investigated in 11 patients submitted to an abdominal surgery. Plasma and urinary levels of aldosterone were increased (x3) significantly (p less than or equal to 0.001) during operation, then decreased gradually in post-operative period, and return to normal values when Na/K ratio is reversed in urines. Relationship between hyperaldosteronism and other changes in endocrine function are established by determination of following hormones: A.C.T.H., cortisol, plasma renin activity (P.R.A.) catecholamines in plasma and urinary levels of 17-ceto, 17-hydroxysteroids and catecholamines. Ethrane anesthesia give a good neurovegetative stability since plasma catecholamines levels are not affected significatively. Plasma aldosterone level is correlated with urinary aldosterone and plasma renin activity. Plasma A.C.T.H. is much more increased at the operative time and decreases rapidly instead of plasma cortisol which decreases more slowly. Relationship of this hyperaldosteronism with anesthetic management, surgical stress intestinal transit disturbances, other endocrine function changes is discussed."}
{"id": "PMID:225967", "title": "[Anaesthesia. Resuscitation problems arising from the surgical treatment of chemodectomas in the carotid fork (author's transl)].", "content": "Chemodectomas in the carotid fork are rare and usually benign tumours. Their removal by surgery creates certain problems in terms of operating technique since they are, anatomically, awkwardly situated. An additional problem arises from loss of blood resulting from their removal and possible cardiac disturbance which might affect the functioning of the carotid sinus should the tumours have been situated in this region. Furthermore, the possible eventuality of having to clamp the internal carotid for a short or even long time, should the operation require it, presupposes a perfect knowledge of the patient's cerebral circulation. Hence, therefore, the necessity of a verification of this circulation by centrolateral carotid arteriography to confirm the permeability of the circle of Willis and a potentially good supply of blood when the blood in the region of the tumour is restricted. It is equally necessary to have a complete record of the general state of the patient's cardiovascular, circulatory, respiratory, renal and neurological conditions. These must, within certain limits, be deemed satisfactory before the decision to operate is taken. Indeed, it is these conditions that will determine the per-operative as well as the post-operative condition of the patient.", "contents": "[Anaesthesia. Resuscitation problems arising from the surgical treatment of chemodectomas in the carotid fork (author's transl)]. Chemodectomas in the carotid fork are rare and usually benign tumours. Their removal by surgery creates certain problems in terms of operating technique since they are, anatomically, awkwardly situated. An additional problem arises from loss of blood resulting from their removal and possible cardiac disturbance which might affect the functioning of the carotid sinus should the tumours have been situated in this region. Furthermore, the possible eventuality of having to clamp the internal carotid for a short or even long time, should the operation require it, presupposes a perfect knowledge of the patient's cerebral circulation. Hence, therefore, the necessity of a verification of this circulation by centrolateral carotid arteriography to confirm the permeability of the circle of Willis and a potentially good supply of blood when the blood in the region of the tumour is restricted. It is equally necessary to have a complete record of the general state of the patient's cardiovascular, circulatory, respiratory, renal and neurological conditions. These must, within certain limits, be deemed satisfactory before the decision to operate is taken. Indeed, it is these conditions that will determine the per-operative as well as the post-operative condition of the patient."}
{"id": "PMID:225973", "title": "[Quantitative analysis of low concentrations of cristobalite in thin layers by x-ray diffraction].", "content": "A new x-ray diffraction procedure for the determination of cristobalite in the presence of amorphous silica is described. The standards are obtained by deposition of thin layers of watery suspensions of cristobalite and amorphous silica mixtures on silver or lead disks or cellulosa filters. Six calibration curves are then calculated to reduce weight and sampling errors. Six mcg of cristobalite mixed with 594 mcg of amorphus silica is the lowest detectable limit. The method may be used for the analysis of both raw materials and respirable dust.", "contents": "[Quantitative analysis of low concentrations of cristobalite in thin layers by x-ray diffraction]. A new x-ray diffraction procedure for the determination of cristobalite in the presence of amorphous silica is described. The standards are obtained by deposition of thin layers of watery suspensions of cristobalite and amorphous silica mixtures on silver or lead disks or cellulosa filters. Six calibration curves are then calculated to reduce weight and sampling errors. Six mcg of cristobalite mixed with 594 mcg of amorphus silica is the lowest detectable limit. The method may be used for the analysis of both raw materials and respirable dust."}
{"id": "PMID:225974", "title": "[Possibility of siliceous pollution in goldsmith workshops].", "content": "The AA. carried out a research in order to determine the entity and the localization of siliceous dust pollution in goldsmith-field in the industrial area near by Valenza Po, Northern Italy. The research put attention just on the microfusion process and it was carried out among factories that attend to this process continuously. In fact the \"scagliola\" is used only during microfusion. It is a sort of mixture containing a high quantity of quartz and cristobalite used for the moulding. Dangerous dusts are caused by the mentioned \"scagliola\" during stripping and mixing. The use of right technical precautionary measures can surely eliminate the risk.", "contents": "[Possibility of siliceous pollution in goldsmith workshops]. The AA. carried out a research in order to determine the entity and the localization of siliceous dust pollution in goldsmith-field in the industrial area near by Valenza Po, Northern Italy. The research put attention just on the microfusion process and it was carried out among factories that attend to this process continuously. In fact the \"scagliola\" is used only during microfusion. It is a sort of mixture containing a high quantity of quartz and cristobalite used for the moulding. Dangerous dusts are caused by the mentioned \"scagliola\" during stripping and mixing. The use of right technical precautionary measures can surely eliminate the risk."}
{"id": "PMID:225975", "title": "[Urinary kallikrein in cadmium-exposed workers].", "content": "The urinary kallikrein activity was determined in a group of 20 young workers exposed to cadmium and to lower concentrations of lead and other toxic agents. Two of them were suffering from labile hypertension. The urinary kallikrein activity of exposed workers was found to be reduced by more than 80% in comparison with a control group.", "contents": "[Urinary kallikrein in cadmium-exposed workers]. The urinary kallikrein activity was determined in a group of 20 young workers exposed to cadmium and to lower concentrations of lead and other toxic agents. Two of them were suffering from labile hypertension. The urinary kallikrein activity of exposed workers was found to be reduced by more than 80% in comparison with a control group."}
{"id": "PMID:225972", "title": "[Radiological diagnosis of primitive hepatic tumors in infants (author's transl)].", "content": "Six primitive hepatic tumours (two benign and four malignant) collected over a period of seven years, are studied. The symptoms were mild or absent in many of the cases, and all were discovered after investigation of hepatomegaly or abdominal mass. The importance of the co-ordinated use of radiological and gammagraphical findings is pointed out.", "contents": "[Radiological diagnosis of primitive hepatic tumors in infants (author's transl)]. Six primitive hepatic tumours (two benign and four malignant) collected over a period of seven years, are studied. The symptoms were mild or absent in many of the cases, and all were discovered after investigation of hepatomegaly or abdominal mass. The importance of the co-ordinated use of radiological and gammagraphical findings is pointed out."}
{"id": "PMID:225978", "title": "[Ultrastructural study in four cases of cutaneous xanthomas in children (author's transl)].", "content": "Three cases are associated with a Reclinghausen disease. Histological findings show typical xanthoma. Electron microscopical study indicates: --numerous intracytoplasmic lipid inclusions of various type (droplets, crystals, concentric lamellar bodies, ceroid granules) in dermal cells (histiocytic foam cells, endothelial cells, Schwann cells, fibroblasts and most cells); --large intranuclear inclusions in some histiocytes containing few lipids droplets; these figures could be compared to a slice of \"petrified wood\"; their significance is as yet unknown (Liesegang rings?).", "contents": "[Ultrastructural study in four cases of cutaneous xanthomas in children (author's transl)]. Three cases are associated with a Reclinghausen disease. Histological findings show typical xanthoma. Electron microscopical study indicates: --numerous intracytoplasmic lipid inclusions of various type (droplets, crystals, concentric lamellar bodies, ceroid granules) in dermal cells (histiocytic foam cells, endothelial cells, Schwann cells, fibroblasts and most cells); --large intranuclear inclusions in some histiocytes containing few lipids droplets; these figures could be compared to a slice of \"petrified wood\"; their significance is as yet unknown (Liesegang rings?)."}
{"id": "PMID:225979", "title": "[Atopic dermatitis: a histologic and radioautographic study (after 3H-thymidine labelling) of epidermal and dermal lesions (author's transl)].", "content": "Skin lesions of atopic dermatitis (A. D.) have been studied histologically and radioautographically after in vitro incorporation of tritiated thymidine. The histopathologic aspects of epidermis in the different types of skin lesions are reviewed. The dermal infiltrate is mononuclear and not very abundant in all types of lesions. An enlargement of the epidermal proliferative compartment has been noticed. Labelled cells are distributed as follows (mean +/- standard deviation) : 46 +/- p. 100 in the basal layer; 37 +/- 6 p. 100 in the epibasal layer; 16 +/- 7 p. 100 in the upper layers. The basal and epidermal labelling indices have been found significantly increased in exudative and lichenified lesions as compared to xerotic areas and normal epidermis. The labelling index of the \"round\" cell infiltrate in the dermis was significantly higher than in irritant patch test reactions (p less than 0.001) but significantly lower than in allergic positive patch test reactions (p less than 0.001). This increased cell proliferation in the dermal infiltrate does not allow definite conclusions about immunopathogenesis of the disease: indeed, a large number of mediators, involved in the inflammatory reactions of A. D. lesions, can modulate cell proliferation.", "contents": "[Atopic dermatitis: a histologic and radioautographic study (after 3H-thymidine labelling) of epidermal and dermal lesions (author's transl)]. Skin lesions of atopic dermatitis (A. D.) have been studied histologically and radioautographically after in vitro incorporation of tritiated thymidine. The histopathologic aspects of epidermis in the different types of skin lesions are reviewed. The dermal infiltrate is mononuclear and not very abundant in all types of lesions. An enlargement of the epidermal proliferative compartment has been noticed. Labelled cells are distributed as follows (mean +/- standard deviation) : 46 +/- p. 100 in the basal layer; 37 +/- 6 p. 100 in the epibasal layer; 16 +/- 7 p. 100 in the upper layers. The basal and epidermal labelling indices have been found significantly increased in exudative and lichenified lesions as compared to xerotic areas and normal epidermis. The labelling index of the \"round\" cell infiltrate in the dermis was significantly higher than in irritant patch test reactions (p less than 0.001) but significantly lower than in allergic positive patch test reactions (p less than 0.001). This increased cell proliferation in the dermal infiltrate does not allow definite conclusions about immunopathogenesis of the disease: indeed, a large number of mediators, involved in the inflammatory reactions of A. D. lesions, can modulate cell proliferation."}
{"id": "PMID:225977", "title": "[Study of a series of 158 parotidectomies and histological problems in mixed tumors of salivary glands (author's transl)].", "content": "About a homogeneous statististic of 158 parotidectomies, authors study repartition parameters of parotid gland tumors. They insist on particular surgical and evolutive problems in relation to histology sometimes very difficult.", "contents": "[Study of a series of 158 parotidectomies and histological problems in mixed tumors of salivary glands (author's transl)]. About a homogeneous statististic of 158 parotidectomies, authors study repartition parameters of parotid gland tumors. They insist on particular surgical and evolutive problems in relation to histology sometimes very difficult."}
{"id": "PMID:225984", "title": "[Importance of corn extract components for the biosynthesis of polymyxin B by B. polymyxa strain 1538].", "content": "The effect of some components of corn-steep liquor, such as biotin, organic nitrogen, inorganic phosphorus and other mineral elements on biosynthesis of polymyxin B by B. polymyxa, strain 1538 was studied. It was found that biotin and organic nitrogen had the most significant effect on the antibiotic accumulation. The effect of inorganic phosphorus and other mineral elements on accumulation of polymyxin by B. polymyxa, strain 1538 was less significant.", "contents": "[Importance of corn extract components for the biosynthesis of polymyxin B by B. polymyxa strain 1538]. The effect of some components of corn-steep liquor, such as biotin, organic nitrogen, inorganic phosphorus and other mineral elements on biosynthesis of polymyxin B by B. polymyxa, strain 1538 was studied. It was found that biotin and organic nitrogen had the most significant effect on the antibiotic accumulation. The effect of inorganic phosphorus and other mineral elements on accumulation of polymyxin by B. polymyxa, strain 1538 was less significant."}
{"id": "PMID:225985", "title": "Streptomycin resistance in a streptomycin-producing microorganism.", "content": "Cell-free extracts of Streptomyces bikiniensis contain an adenosine 5'-triphosphate-dependent kinase which inactivates streptomycin (Sm) and dihydrostreptomycin by phosphorylation. The products have been identified as streptomycin 6-phosphate and dihydrostreptomycin 6-phosphate. Activity was not present in logarithmic-phase cells, which were susceptible to 25 mug of Sm per ml. In stationary-phase cells, activity appeared 12 h before detectable Sm in the medium. These cells were resistant to more than 200 mug of Sm per ml. Certain S. bikiniensis isolates selected from cultures treated with acriflavine or ethidium bromide lost the ability to produce Sm and became susceptible to 10 mug of Sm per ml throughout their growth. Cell-free extracts of the dye-treated isolates did not inactivate Sm and lacked streptomycin kinase activity at all stages in development. Ribosomes from resistant cells bound the same amount of [(3)H]dihydrostreptomycin as ribosomes from susceptible cells, and there was no correlation between the uptake of [(3)H]dihydrostreptomycin and resistance. The Sm-inactivating enzyme was identified as streptomycin-6-kinase. These results suggest that phosphorylation by streptomycin-6-kinase is a major factor in resistance in S. bikiniensis.", "contents": "Streptomycin resistance in a streptomycin-producing microorganism. Cell-free extracts of Streptomyces bikiniensis contain an adenosine 5'-triphosphate-dependent kinase which inactivates streptomycin (Sm) and dihydrostreptomycin by phosphorylation. The products have been identified as streptomycin 6-phosphate and dihydrostreptomycin 6-phosphate. Activity was not present in logarithmic-phase cells, which were susceptible to 25 mug of Sm per ml. In stationary-phase cells, activity appeared 12 h before detectable Sm in the medium. These cells were resistant to more than 200 mug of Sm per ml. Certain S. bikiniensis isolates selected from cultures treated with acriflavine or ethidium bromide lost the ability to produce Sm and became susceptible to 10 mug of Sm per ml throughout their growth. Cell-free extracts of the dye-treated isolates did not inactivate Sm and lacked streptomycin kinase activity at all stages in development. Ribosomes from resistant cells bound the same amount of [(3)H]dihydrostreptomycin as ribosomes from susceptible cells, and there was no correlation between the uptake of [(3)H]dihydrostreptomycin and resistance. The Sm-inactivating enzyme was identified as streptomycin-6-kinase. These results suggest that phosphorylation by streptomycin-6-kinase is a major factor in resistance in S. bikiniensis."}
{"id": "PMID:225986", "title": "Effects of amphotericin B and its methyl ester on the antiviral activity of polyinosinic:polycytidylic acid.", "content": "Since the macrolide polyene antibiotics, amphotericin B (AmB) and its methyl ester (AmBME), augment interferon production by polyriboinosinic:polyribocytidylic acid [poly(I):poly(C)] in vitro, experiments were undertaken to determine how AmB and AmBME affect the antiviral activity of poly(I):poly(C) and interferon. AmBME increased the direct antiviral activity of poly(I):poly(C) 10(2)-to 10(4)-fold in L929, Flow 6000, and T98G cells. Viral replication, measured by either direct plaque formation or virus yield, was markedly reduced. Serum interferon levels in mice induced by poly(I):poly(C) were enhanced by concomitant treatment with AmB. However, the therapeutic effects of poly(I):poly(C) in encephalomyocarditis and Semliki Forest virus infections were not augmented by combined treatment with poly(I):poly(C) and AmB. In vitro, the antiviral effects of exogenous interferon were markedly inhibited by AmB and AmBME. This inhibition may have contributed to the adverse effects of the macrolide polyenes in encephalomyocarditis and Semliki Forest virus infections in vivo. These findings further substantiate the effectiveness of macrolide polyenes in augmenting cellular penetration of macromolecules. However, therapeutic application may be limited by the complex interactions which occur between compounds administered in vivo.", "contents": "Effects of amphotericin B and its methyl ester on the antiviral activity of polyinosinic:polycytidylic acid. Since the macrolide polyene antibiotics, amphotericin B (AmB) and its methyl ester (AmBME), augment interferon production by polyriboinosinic:polyribocytidylic acid [poly(I):poly(C)] in vitro, experiments were undertaken to determine how AmB and AmBME affect the antiviral activity of poly(I):poly(C) and interferon. AmBME increased the direct antiviral activity of poly(I):poly(C) 10(2)-to 10(4)-fold in L929, Flow 6000, and T98G cells. Viral replication, measured by either direct plaque formation or virus yield, was markedly reduced. Serum interferon levels in mice induced by poly(I):poly(C) were enhanced by concomitant treatment with AmB. However, the therapeutic effects of poly(I):poly(C) in encephalomyocarditis and Semliki Forest virus infections were not augmented by combined treatment with poly(I):poly(C) and AmB. In vitro, the antiviral effects of exogenous interferon were markedly inhibited by AmB and AmBME. This inhibition may have contributed to the adverse effects of the macrolide polyenes in encephalomyocarditis and Semliki Forest virus infections in vivo. These findings further substantiate the effectiveness of macrolide polyenes in augmenting cellular penetration of macromolecules. However, therapeutic application may be limited by the complex interactions which occur between compounds administered in vivo."}
{"id": "PMID:225987", "title": "Pharmacokinetics of E-5-(2-bromovinyl)-2'-deoxyuridine in mice.", "content": "The pharmacokinetics of the newly developed anti-herpes agent, E-5-(2-bromovinyl)-2'-deoxyuridine, was compared with that of the standard anti-herpes drug 5-iodo-2'-deoxyuridine. Both compounds were administered to mice at 100 mg/kg by either the intraperitoneal, subcutaneous, or oral route. The active blood drug levels achieved by E-5-(2-bromovinyl)-2'-deoxyuridine were considerably higher than those attained by 5-iodo-2'-deoxyuridine (serum peak concentrations: 40 to 100 and 4 to 10 mug/ml, respectively). Active blood drug levels could still be found 320 min after oral administration of E-5-(2-bromovinyl)-2'-deoxyuridine.", "contents": "Pharmacokinetics of E-5-(2-bromovinyl)-2'-deoxyuridine in mice. The pharmacokinetics of the newly developed anti-herpes agent, E-5-(2-bromovinyl)-2'-deoxyuridine, was compared with that of the standard anti-herpes drug 5-iodo-2'-deoxyuridine. Both compounds were administered to mice at 100 mg/kg by either the intraperitoneal, subcutaneous, or oral route. The active blood drug levels achieved by E-5-(2-bromovinyl)-2'-deoxyuridine were considerably higher than those attained by 5-iodo-2'-deoxyuridine (serum peak concentrations: 40 to 100 and 4 to 10 mug/ml, respectively). Active blood drug levels could still be found 320 min after oral administration of E-5-(2-bromovinyl)-2'-deoxyuridine."}
{"id": "PMID:225988", "title": "Effect of heat treatment on the performance of tryptose-sulfite-cycloserine agar for enumeration of Clostridium perfringens.", "content": "Dissolving dehydrated tryptose-sulfite-cycloserine agar by only boiling or microwaving was found to inhibit Clostridium perfringens colony development in pour plates when compared with C. perfringens recovery in tryptose-sulfite-cycloserine agar prepared by autoclaving.", "contents": "Effect of heat treatment on the performance of tryptose-sulfite-cycloserine agar for enumeration of Clostridium perfringens. Dissolving dehydrated tryptose-sulfite-cycloserine agar by only boiling or microwaving was found to inhibit Clostridium perfringens colony development in pour plates when compared with C. perfringens recovery in tryptose-sulfite-cycloserine agar prepared by autoclaving."}
{"id": "PMID:225983", "title": "Evaluation of beta-subunit chorionic gonadotropin as an aid in diagnosis of trophoblastic disease.", "content": "The advent of the radioimmunoassay of Beta subunit chorionic gonadotropin (BhCG) has eliminated a major problem in following the patient with gestational trophoblastic neoplasia (GTN). Whole hCG cross reacts with luteinizing hormone (hLH) causing difficulties when GTN patient titers fall to levels coincidental with pituitary levels of hLH. The use of the Beta subunit of hCG in radioimmunoassay has eliminated this problem because there is essentially no cross reaction between the B-subunit of the hCG and hLH. A review of the use of this sensitive assay in the management of patients with GTN is presented.", "contents": "Evaluation of beta-subunit chorionic gonadotropin as an aid in diagnosis of trophoblastic disease. The advent of the radioimmunoassay of Beta subunit chorionic gonadotropin (BhCG) has eliminated a major problem in following the patient with gestational trophoblastic neoplasia (GTN). Whole hCG cross reacts with luteinizing hormone (hLH) causing difficulties when GTN patient titers fall to levels coincidental with pituitary levels of hLH. The use of the Beta subunit of hCG in radioimmunoassay has eliminated this problem because there is essentially no cross reaction between the B-subunit of the hCG and hLH. A review of the use of this sensitive assay in the management of patients with GTN is presented."}
{"id": "PMID:225989", "title": "Glutaraldehyde inactivation of exotic animal viruses in swine heart tissue.", "content": "Glutaraldehyde, 0.2%, in a 1:100 (wt/vol) ratio, inactivated four animal viruses (foot-and-mouth disease, swine vesicular disease, African swine fever, hog cholera) in swine heart tissues during 11-day exposures at 22 to 26 degrees C.", "contents": "Glutaraldehyde inactivation of exotic animal viruses in swine heart tissue. Glutaraldehyde, 0.2%, in a 1:100 (wt/vol) ratio, inactivated four animal viruses (foot-and-mouth disease, swine vesicular disease, African swine fever, hog cholera) in swine heart tissues during 11-day exposures at 22 to 26 degrees C."}
{"id": "PMID:225990", "title": "Microbial cleavage of various organophosphorus insecticides.", "content": "Bacteria able to utilize Aspon, Azodrin, Dasanit, diazinon, malathion, Orthene, parathion, Trithion, dimethoate, Dylox, methyl parathion, and Vapona as sole phosphorus sources were isolated from soil and sewage. Individual isolates used from 3 to 10 of these insecticides as sole phosphorus sources. The extent of growth of two Pseudomonas strains in media containing diazinon and malathion was in the range expected from the amount of insecticide supplied, and their proliferation resulted in disappearance of the chemical. Resting cells of the pseudomonads derived from cultures grown on diazinon or malathion but not orthophosphate caused extensive destruction of these two organophosphates in the presence or absence of chloramphenicol. Extracts of the two bacteria derived from organophosphate-grown cultures catalyzed the disappearance of Aspon, Azodrin, Dasanit, diazinon, malathion, Orthene, parathion, and Trithion but not dimethoate, Dylox, methyl parathion, and Vapona. Results from gas chromatographic analysis suggested that the extracts formed dimethyl phosphate from azodrin, dimethyl phosphorodithioate from malathion, diethyl phosphorodithioate from Trithion, and diethyl phosphorothioate from Dasanit, diazinon, and parathion. Dimethyl phosphate, dimethyl phosphorothioate , dimethyl phosphorodithioate, diethyl phosphate, and diethyl phosphorothioate were not used by the pseudomonads as sole phosphorus sources.", "contents": "Microbial cleavage of various organophosphorus insecticides. Bacteria able to utilize Aspon, Azodrin, Dasanit, diazinon, malathion, Orthene, parathion, Trithion, dimethoate, Dylox, methyl parathion, and Vapona as sole phosphorus sources were isolated from soil and sewage. Individual isolates used from 3 to 10 of these insecticides as sole phosphorus sources. The extent of growth of two Pseudomonas strains in media containing diazinon and malathion was in the range expected from the amount of insecticide supplied, and their proliferation resulted in disappearance of the chemical. Resting cells of the pseudomonads derived from cultures grown on diazinon or malathion but not orthophosphate caused extensive destruction of these two organophosphates in the presence or absence of chloramphenicol. Extracts of the two bacteria derived from organophosphate-grown cultures catalyzed the disappearance of Aspon, Azodrin, Dasanit, diazinon, malathion, Orthene, parathion, and Trithion but not dimethoate, Dylox, methyl parathion, and Vapona. Results from gas chromatographic analysis suggested that the extracts formed dimethyl phosphate from azodrin, dimethyl phosphorodithioate from malathion, diethyl phosphorodithioate from Trithion, and diethyl phosphorothioate from Dasanit, diazinon, and parathion. Dimethyl phosphate, dimethyl phosphorothioate , dimethyl phosphorodithioate, diethyl phosphate, and diethyl phosphorothioate were not used by the pseudomonads as sole phosphorus sources."}
{"id": "PMID:225991", "title": "Raffinose increases sporulation and enterotoxin production by Clostridium perfringens type A.", "content": "Replacement of starch with raffinose in Duncan and Strong sporulation medium improved percent sporulation in six of eight strains tested. Enterotoxin concentration in cell extracts was increased in the case of four of five known enterotoxin-positive strains. With strain NCTC 10240, levels of 0.3, 0.4, and 0.5% raffinose produced the highest enterotoxin concentration 300 to 320 micrograms of enterotoxin per mg of cell extract protein. At a level of 0.4% raffinose the highest enterotoxin concentration in cell extracts of NCTC 10240 occurred after 8 h of growth in Duncan and Strong medium. Enterotoxin produced in the presence of starch or raffinose by three separate strains all migrated at similar Rm by polyacrylamide gel electrophoresis.", "contents": "Raffinose increases sporulation and enterotoxin production by Clostridium perfringens type A. Replacement of starch with raffinose in Duncan and Strong sporulation medium improved percent sporulation in six of eight strains tested. Enterotoxin concentration in cell extracts was increased in the case of four of five known enterotoxin-positive strains. With strain NCTC 10240, levels of 0.3, 0.4, and 0.5% raffinose produced the highest enterotoxin concentration 300 to 320 micrograms of enterotoxin per mg of cell extract protein. At a level of 0.4% raffinose the highest enterotoxin concentration in cell extracts of NCTC 10240 occurred after 8 h of growth in Duncan and Strong medium. Enterotoxin produced in the presence of starch or raffinose by three separate strains all migrated at similar Rm by polyacrylamide gel electrophoresis."}
{"id": "PMID:225992", "title": "Method of soil column preparation for the evaluation of viral transport.", "content": "A method for packing soil columns to investigate viral transport phenomena is described. The columns were 10 cm in diameter and ranged from 33 to 100 cm in length. Field conditions of the soil, including bulk density and profile, were reproduced in columns. Ionic gradients resulting from sequential applications of wastewater and distilled water affected the movement of poliovirus I (Chat) through soil. Compared with 33-cm- and 66-cm-length columns, lower concentrations of infectious virions were observed in the percolates from 100-cm soil columns. These results may be attributed to the greater pore volume in the longer columns (the greater volume of soil contained in these columns), whereas the volume of liquid applied was constant for all columns.", "contents": "Method of soil column preparation for the evaluation of viral transport. A method for packing soil columns to investigate viral transport phenomena is described. The columns were 10 cm in diameter and ranged from 33 to 100 cm in length. Field conditions of the soil, including bulk density and profile, were reproduced in columns. Ionic gradients resulting from sequential applications of wastewater and distilled water affected the movement of poliovirus I (Chat) through soil. Compared with 33-cm- and 66-cm-length columns, lower concentrations of infectious virions were observed in the percolates from 100-cm soil columns. These results may be attributed to the greater pore volume in the longer columns (the greater volume of soil contained in these columns), whereas the volume of liquid applied was constant for all columns."}
{"id": "PMID:225993", "title": "Survival of poliovirus within organic solids during chlorination.", "content": "Poliovirus in fecal homogenates was used to determine the protection against inactivation by chlorination afforded virus that was occluded within particulates. Virus that was closely associated with or occluded within small fecal particulates was protected. A fourfold increase in combined residual chlorine was required to achieve the same degree of inactivation for occluded virus as for free or secondarily adsorbed virus. A combined chlorine residual of 6.6 mg/liter was necessary to achieve 50% inactivation in 15 min at pH 8.0 and 22 degrees C in a particulate suspension containing occluded virus compared to 1.4 mg/liter for free virus. These differences were found to be relatively small compared to differences due to the presence of dissolved organics or between free and combined chlorine residuals. The results suggest different mechanisms of protection due to adsorption and occlusion.", "contents": "Survival of poliovirus within organic solids during chlorination. Poliovirus in fecal homogenates was used to determine the protection against inactivation by chlorination afforded virus that was occluded within particulates. Virus that was closely associated with or occluded within small fecal particulates was protected. A fourfold increase in combined residual chlorine was required to achieve the same degree of inactivation for occluded virus as for free or secondarily adsorbed virus. A combined chlorine residual of 6.6 mg/liter was necessary to achieve 50% inactivation in 15 min at pH 8.0 and 22 degrees C in a particulate suspension containing occluded virus compared to 1.4 mg/liter for free virus. These differences were found to be relatively small compared to differences due to the presence of dissolved organics or between free and combined chlorine residuals. The results suggest different mechanisms of protection due to adsorption and occlusion."}
{"id": "PMID:226002", "title": "Granular cell basal cell carcinoma. A distinct histopathologic entity.", "content": "In two cases of basal cell carcinoma with prominent granular cell features, light microscopic examination showed a tumor with the general configuration of a nodular basal cell carcinoma. Focally, there were masses of cells with eosinophilic, granular cytoplasm and large cytoplasmic inclusions, strongly suggestive of granular cell myoblastoma. Ultrastructural observations in one case showed numerous lysosome-like organelles that were similar to those described for granular cell myoblastoma, but were identical to those described for the granular cell variant of ameloblastoma, a tumor that frequently resembles basal cell carcinoma. Additional features included tonofilaments and desmosomes, both of which support an epithelial origin for the granular cells in this rare variant of basal cell carcinoma.", "contents": "Granular cell basal cell carcinoma. A distinct histopathologic entity. In two cases of basal cell carcinoma with prominent granular cell features, light microscopic examination showed a tumor with the general configuration of a nodular basal cell carcinoma. Focally, there were masses of cells with eosinophilic, granular cytoplasm and large cytoplasmic inclusions, strongly suggestive of granular cell myoblastoma. Ultrastructural observations in one case showed numerous lysosome-like organelles that were similar to those described for granular cell myoblastoma, but were identical to those described for the granular cell variant of ameloblastoma, a tumor that frequently resembles basal cell carcinoma. Additional features included tonofilaments and desmosomes, both of which support an epithelial origin for the granular cells in this rare variant of basal cell carcinoma."}
{"id": "PMID:226003", "title": "Metastatic ductal carcinoma of the parotid gland in a patient with sarcoidosis.", "content": "A 38-year-old man with a history of sarcoidosis and ductal carcinoma of the parotid had metastasis to the pleura and skin. This skin metastasis resembled carcinoma of the breast. There is a possibility of sarcoidosis with its depressed cellular immunity predisposing to malignancy.", "contents": "Metastatic ductal carcinoma of the parotid gland in a patient with sarcoidosis. A 38-year-old man with a history of sarcoidosis and ductal carcinoma of the parotid had metastasis to the pleura and skin. This skin metastasis resembled carcinoma of the breast. There is a possibility of sarcoidosis with its depressed cellular immunity predisposing to malignancy."}
{"id": "PMID:226004", "title": "Cytomegalovirus and blood transfusion in neonates.", "content": "A fatal case of neonatal cytomegalovirus (CMV) infection attributed to exchange transfusion is described. The incidence of CMV transmission by exchange and other neonatal transfusion was studied, and the use of CMV antibody-free blood for these procedures was shown to be effective in preventing CMV infection in neonates.", "contents": "Cytomegalovirus and blood transfusion in neonates. A fatal case of neonatal cytomegalovirus (CMV) infection attributed to exchange transfusion is described. The incidence of CMV transmission by exchange and other neonatal transfusion was studied, and the use of CMV antibody-free blood for these procedures was shown to be effective in preventing CMV infection in neonates."}
{"id": "PMID:226005", "title": "Toxic effects of dietary polybrominated biphenyls on mink.", "content": "Serial levels of fireMaster FF-1, a commercial mixture of polybrominated biphenyls (PBB), and tissues from chickens and a cow that had previously consumed PBB were fed to mink to ascertain the chronic effects of the commercial and \"metabolized\" form of this compound on mink. Diets that contained 6.25 ppm (or more) PBB were lethal to adult mink within 10 months. One to 2.5 ppm dietary PBB fed for 9 months had an adverse effect on litter size, kit weight at birth, and kit survival. The data suggest that the PBB derived from contaminated beef and poultry was more toxic than the original PBB. The clinical signs of PBB poisoning in mink were food rejection, weight loss, and unthrifty appearance, and fatty infiltration of the liver. Based on these findings, mink must be considered highly susceptible to PBB toxicity. PBB residue levels 60 times the amount in the diet were found in the adipose tissue of the PBB-treated animals.", "contents": "Toxic effects of dietary polybrominated biphenyls on mink. Serial levels of fireMaster FF-1, a commercial mixture of polybrominated biphenyls (PBB), and tissues from chickens and a cow that had previously consumed PBB were fed to mink to ascertain the chronic effects of the commercial and \"metabolized\" form of this compound on mink. Diets that contained 6.25 ppm (or more) PBB were lethal to adult mink within 10 months. One to 2.5 ppm dietary PBB fed for 9 months had an adverse effect on litter size, kit weight at birth, and kit survival. The data suggest that the PBB derived from contaminated beef and poultry was more toxic than the original PBB. The clinical signs of PBB poisoning in mink were food rejection, weight loss, and unthrifty appearance, and fatty infiltration of the liver. Based on these findings, mink must be considered highly susceptible to PBB toxicity. PBB residue levels 60 times the amount in the diet were found in the adipose tissue of the PBB-treated animals."}
{"id": "PMID:226011", "title": "Collagenase production by rheumatoid synovial cells: morphological and immunohistochemical studies of the dendritic cell.", "content": "The dendritic cells of dissociated, adherent rheumatoid synovial cell cultures are recognised by their distinctive morphological features--compact cytoplasm around the nucleus and long, branched cytoplasmic extensions. Such cells usually composed approximately 10% of the total adherent cell population but could vary from as few as 2% to as many as 40% with different synovial specimens. Histological studies have shown the cells to contain many mitochondria and large, spherical cytoplasmic inclusions which often distort the dendritic extensions. Although lysosomes were observed, no evidence for phagocytic activity was obtained. Immunolocalisation studies by means of a monospecific antibody to human collagenase have shown that the dendritic cell attached to a collagenous substratum produces and releases this enzyme in vitro. In contrast collagenase was detected in only a few of the fibroblast- and macrophage-like cells, and it was always intracellular. It is proposed that the dendritic cell may have an important role in the pathophysiology of the rheumatoid joint, particularly with regard to collagenase-mediated cartilage destruction.", "contents": "Collagenase production by rheumatoid synovial cells: morphological and immunohistochemical studies of the dendritic cell. The dendritic cells of dissociated, adherent rheumatoid synovial cell cultures are recognised by their distinctive morphological features--compact cytoplasm around the nucleus and long, branched cytoplasmic extensions. Such cells usually composed approximately 10% of the total adherent cell population but could vary from as few as 2% to as many as 40% with different synovial specimens. Histological studies have shown the cells to contain many mitochondria and large, spherical cytoplasmic inclusions which often distort the dendritic extensions. Although lysosomes were observed, no evidence for phagocytic activity was obtained. Immunolocalisation studies by means of a monospecific antibody to human collagenase have shown that the dendritic cell attached to a collagenous substratum produces and releases this enzyme in vitro. In contrast collagenase was detected in only a few of the fibroblast- and macrophage-like cells, and it was always intracellular. It is proposed that the dendritic cell may have an important role in the pathophysiology of the rheumatoid joint, particularly with regard to collagenase-mediated cartilage destruction."}
{"id": "PMID:226013", "title": "Calcium infusion: a new provocative test for insulinomas.", "content": "Calcium gluconate (10 mg Ca(++)/kg) was administered intravenously over a 2-hour period to 16 adult patients who were evaluated for hypoglycemia. In nine of ten patients with benign or malignant insulinomas (eight proven at operation, and two with positive chemical tests and angiographic localization awaiting operation), significant hypoglycemia and hyperinsulinemia occurred within 60 to 90 minutes after the start of the calcium infusion. Serum proinsulin and Cpeptide concentrations increased at the time of the calciuminduced hyperinsulinemia in several patients in whom these parameters were studied. The one individual who did not respond to the calcium infusion was found to have a benign insulinoma. His basal glucose/insulin ratio of 0.64 was the lowest of the insulinoma group and thus his failure to respond to calcium may indicate that his tumor was secreting maximally at the time of the infusion. Following successful removal of the insulinoma, calcium infusion did not result in changes in serum glucose or insulin concentrations (tested in five patients). In contrast, neither a patient with pathologically documented islet cell hyperplasia, five others with reactive, fupctional or drug-induced hypoglycemia, nor four healthy volunteers showed any changes in circulating glucose or insulin levels while receiving calcium intravenously. Calcium infusion is a safe, rapid and effective provocative test for the diagnosis of insulin-secreting, islet cell tumors of the pancreas.", "contents": "Calcium infusion: a new provocative test for insulinomas. Calcium gluconate (10 mg Ca(++)/kg) was administered intravenously over a 2-hour period to 16 adult patients who were evaluated for hypoglycemia. In nine of ten patients with benign or malignant insulinomas (eight proven at operation, and two with positive chemical tests and angiographic localization awaiting operation), significant hypoglycemia and hyperinsulinemia occurred within 60 to 90 minutes after the start of the calcium infusion. Serum proinsulin and Cpeptide concentrations increased at the time of the calciuminduced hyperinsulinemia in several patients in whom these parameters were studied. The one individual who did not respond to the calcium infusion was found to have a benign insulinoma. His basal glucose/insulin ratio of 0.64 was the lowest of the insulinoma group and thus his failure to respond to calcium may indicate that his tumor was secreting maximally at the time of the infusion. Following successful removal of the insulinoma, calcium infusion did not result in changes in serum glucose or insulin concentrations (tested in five patients). In contrast, neither a patient with pathologically documented islet cell hyperplasia, five others with reactive, fupctional or drug-induced hypoglycemia, nor four healthy volunteers showed any changes in circulating glucose or insulin levels while receiving calcium intravenously. Calcium infusion is a safe, rapid and effective provocative test for the diagnosis of insulin-secreting, islet cell tumors of the pancreas."}
{"id": "PMID:226014", "title": "New aspects of androgens, prolactin, and ACTH interaction in men.", "content": "Some endocrine effects of prolactin (PRL), ACTH, and corticosteroids in testicular function were evaluated by measuring, in normal men, the effects of short-term experimental stimulation and suppression of either plasma PRL levels or adrenal function on plasma androgen profile. PRL levels were increased by administration of metoclopramide or sulpiride or suppressed with bromocryptine. Long-acting testosterone (T) was injected at 8 a.m. on one day in a control period and during a 9-day period of metoclopramide administration. PRL increase was accompanied by a rise in plasma 17-hydroxyprogesterone and T, whereas PRL suppression induced an increase in 5 alpha-dihydrotestosterone (DHT) plasma levels. Peripheral converions of T into DHT and androstenedione, noted after T injection, decreased during concomitant metoclopramide administration. Plasma testicular androgen levels were lowered after long-acting ACTH injections as well as after 24-hr cortisol administration, but the metoclopramide-induced PRL increase appeared to prevent the suppressive effects of ACTH on plasma T. A low-dose dexamethasone treatment did not modify testicular androgen levels. Experimentally induced hyperprolactinemia may have a stimulatory effect on testicular androgen secretion as well as a lowering action on 5 alpha reduction and oxidative T metabolism in man. On the other hand, ACTH-induced androgen suppression seems to be mediated through high circulating levels of corticosteroids; furthermore, PRL and corticosteroids might have reciprocal influences that modulate their effects on testicular function.", "contents": "New aspects of androgens, prolactin, and ACTH interaction in men. Some endocrine effects of prolactin (PRL), ACTH, and corticosteroids in testicular function were evaluated by measuring, in normal men, the effects of short-term experimental stimulation and suppression of either plasma PRL levels or adrenal function on plasma androgen profile. PRL levels were increased by administration of metoclopramide or sulpiride or suppressed with bromocryptine. Long-acting testosterone (T) was injected at 8 a.m. on one day in a control period and during a 9-day period of metoclopramide administration. PRL increase was accompanied by a rise in plasma 17-hydroxyprogesterone and T, whereas PRL suppression induced an increase in 5 alpha-dihydrotestosterone (DHT) plasma levels. Peripheral converions of T into DHT and androstenedione, noted after T injection, decreased during concomitant metoclopramide administration. Plasma testicular androgen levels were lowered after long-acting ACTH injections as well as after 24-hr cortisol administration, but the metoclopramide-induced PRL increase appeared to prevent the suppressive effects of ACTH on plasma T. A low-dose dexamethasone treatment did not modify testicular androgen levels. Experimentally induced hyperprolactinemia may have a stimulatory effect on testicular androgen secretion as well as a lowering action on 5 alpha reduction and oxidative T metabolism in man. On the other hand, ACTH-induced androgen suppression seems to be mediated through high circulating levels of corticosteroids; furthermore, PRL and corticosteroids might have reciprocal influences that modulate their effects on testicular function."}
{"id": "PMID:226015", "title": "Pyrimidine synthetic enzymes of the rat testis and epididymis following unilateral vasectomy.", "content": "The de novo pyrimidine synthetic enzyme, aspartate carbamyltransferase, and the two pyrimidine salvage enzymes, uridine and thymidine kinases, of the rat testis and epididymis were measured 1, 2, 4, 6, 8, and 10 wk following unilateral vasectomy. Vasectomy had no effect on organ wet weights and on testicular and epididymal asparate carbamyltransferase and thymidine kinase activities. Increases in the uridine kinase activity of the caput epididymidis at 2 wk and of the cauda epididymidis from the second to the sixth weeks were the only significant enzymatic changes observed.", "contents": "Pyrimidine synthetic enzymes of the rat testis and epididymis following unilateral vasectomy. The de novo pyrimidine synthetic enzyme, aspartate carbamyltransferase, and the two pyrimidine salvage enzymes, uridine and thymidine kinases, of the rat testis and epididymis were measured 1, 2, 4, 6, 8, and 10 wk following unilateral vasectomy. Vasectomy had no effect on organ wet weights and on testicular and epididymal asparate carbamyltransferase and thymidine kinase activities. Increases in the uridine kinase activity of the caput epididymidis at 2 wk and of the cauda epididymidis from the second to the sixth weeks were the only significant enzymatic changes observed."}
{"id": "PMID:226016", "title": "Effect of calcium concentration, isoproterenol, and McN-2165 on fetal rat heart rate and cyclic AMP level.", "content": "The fetal rat heart in organ culture was used to study the interaction of calcium with the cardioactive agents. McN-2165 is an agent that produces negative chronotropism and elevation in cyclic AMP levels in this preparation. A concentration of 2.76 mM calcium ion antagonized the negative chronotropic action and prevented the cyclic AMP elevation produced by this agent. Positive chronotropic actions of isoproterenol were prevented by decreasing the calcium level below 1.84 mM.", "contents": "Effect of calcium concentration, isoproterenol, and McN-2165 on fetal rat heart rate and cyclic AMP level. The fetal rat heart in organ culture was used to study the interaction of calcium with the cardioactive agents. McN-2165 is an agent that produces negative chronotropism and elevation in cyclic AMP levels in this preparation. A concentration of 2.76 mM calcium ion antagonized the negative chronotropic action and prevented the cyclic AMP elevation produced by this agent. Positive chronotropic actions of isoproterenol were prevented by decreasing the calcium level below 1.84 mM."}
{"id": "PMID:226017", "title": "The action of nicotine on the pituitary-adrenal cortical axis.", "content": "Nicotine was found to raise dramatically plasma corticosterone levels in a dose-dependent manner. Plasma corticosterone time course for the 100 microgram/kg dose of nicotine produced an initial increase in corticosterone elevation which did not return towards control levels until after 30 min. The 200 and 500 microgram/kg doses, however, indicated a biphasic response for nicotine-induced steroid secretion. The first steroid peak occurred 1-15 min after nicotine administration and was followed by a greater elevation at 20 min. Plasma nicotine levels did not show the same biphasic pattern. The nicotine-induced plasma steroid elevation was completely abolished by hypophysectomy, indicating that the response to nicotine must be mediated through ACTH release from the anterior pituitary. The administration of exogenous ACTH to rats pretreated with betamethasone was found to result in a biphasic plasma steroid elevation similar to that seen after injection of 200 microgram/kg nicotine. It was postulated that this may reflect a differential response of the adrenal cortex to a single ACTH outflow.", "contents": "The action of nicotine on the pituitary-adrenal cortical axis. Nicotine was found to raise dramatically plasma corticosterone levels in a dose-dependent manner. Plasma corticosterone time course for the 100 microgram/kg dose of nicotine produced an initial increase in corticosterone elevation which did not return towards control levels until after 30 min. The 200 and 500 microgram/kg doses, however, indicated a biphasic response for nicotine-induced steroid secretion. The first steroid peak occurred 1-15 min after nicotine administration and was followed by a greater elevation at 20 min. Plasma nicotine levels did not show the same biphasic pattern. The nicotine-induced plasma steroid elevation was completely abolished by hypophysectomy, indicating that the response to nicotine must be mediated through ACTH release from the anterior pituitary. The administration of exogenous ACTH to rats pretreated with betamethasone was found to result in a biphasic plasma steroid elevation similar to that seen after injection of 200 microgram/kg nicotine. It was postulated that this may reflect a differential response of the adrenal cortex to a single ACTH outflow."}
{"id": "PMID:226018", "title": "Effects of betamethasone on the stimulation of corticosterone secretion in rats.", "content": "The effects of betamethasone on the elevation of rat plasma corticosterone levels by nicotine (400 microgram/kg s.c.), urethane anaesthesia and psychological stress have been studied. Betamethasone pretreatment (5 mg/kg given in the drinking water over 24 hr) initially suppressed the response to all three stimuli but, after 24 hr, only the response to urethane remained totally suppressed. Nicotine administered at this time to the urethane anaesthetised rats caused an increase in plasma corticosterone, apparently by stimulation of the autonomic nervous system. The results suggest that, following betamethasone, there is a prolonged delay in the recovery of the specific mechanism through which urethane stimulates pituitary-adrenal function rather than a total blockade of the effects of all stressful or chemical stimuli on ACTH secretion.", "contents": "Effects of betamethasone on the stimulation of corticosterone secretion in rats. The effects of betamethasone on the elevation of rat plasma corticosterone levels by nicotine (400 microgram/kg s.c.), urethane anaesthesia and psychological stress have been studied. Betamethasone pretreatment (5 mg/kg given in the drinking water over 24 hr) initially suppressed the response to all three stimuli but, after 24 hr, only the response to urethane remained totally suppressed. Nicotine administered at this time to the urethane anaesthetised rats caused an increase in plasma corticosterone, apparently by stimulation of the autonomic nervous system. The results suggest that, following betamethasone, there is a prolonged delay in the recovery of the specific mechanism through which urethane stimulates pituitary-adrenal function rather than a total blockade of the effects of all stressful or chemical stimuli on ACTH secretion."}
{"id": "PMID:226019", "title": "Effects of streptomycin on the cortical neurons in the cat.", "content": "Data concerning the effects of streptomycin application on the brain cortex are very scarce and nonconcordant, despite routine intra-thecal administration of this drug. Experiments peformed in 15 adult cats permitted us to observed that application of streptomycin sulphate on the brain cortex leads to a real cortical depression, demonstrated by the disappearance of spontaneous spikes, lack of cortical fast activity and lack of hippocampal theta activity. The direct cortical response disappears too and sometimes even the transmission towards the deep structures of neuronal activation induced by high intensity or repetitive stimuli. The depressing activity of streptomycin resembles to a spreading depression, with an effect limited only to the hemisphere where the drug is applied. The difference between our results and those of other authors can be explained by the different degree of purity of the streptomycin used in the experiments.", "contents": "Effects of streptomycin on the cortical neurons in the cat. Data concerning the effects of streptomycin application on the brain cortex are very scarce and nonconcordant, despite routine intra-thecal administration of this drug. Experiments peformed in 15 adult cats permitted us to observed that application of streptomycin sulphate on the brain cortex leads to a real cortical depression, demonstrated by the disappearance of spontaneous spikes, lack of cortical fast activity and lack of hippocampal theta activity. The direct cortical response disappears too and sometimes even the transmission towards the deep structures of neuronal activation induced by high intensity or repetitive stimuli. The depressing activity of streptomycin resembles to a spreading depression, with an effect limited only to the hemisphere where the drug is applied. The difference between our results and those of other authors can be explained by the different degree of purity of the streptomycin used in the experiments."}
{"id": "PMID:226020", "title": "Comparison of the inhibitory effects of acetylsalicylic acid and trifusal on enzymes related to thrombosis.", "content": "Triflusal is a new antithrombotic agent, structurally similar to acetylsalicylic acid (ASA), which has been shown to possess a different pharmacological profile, suggesting a different mechanism of action for both compounds. To confirm this hypothesis we have studied, comparatively, the inhibition by  triflusal and ASA of the activity of several enzymes involved in the equilibrium of platelet haemostasis, namely, prostaglandin-synthetase system (PG-synthetase), cyclo-oxygenase, thromboxane-synthetase and cAMP-phosphodiesterase. Results indicate that trilfusal is 60% less potent as inhibitor of cyclooxygenase (biological method) and of prostaglandin biosynthesis (spectrophotometric method ) than ASA. On the contrary, triflusal is five times more potent than ASA as inhibitor of cAMP phosphodoesterase. Inhibition of thromboxane-synthetase by both compounds is negligible and without physiological significance. These results suggest a mechanism of action of trifusal that might explain the different pharmacological profile between triflusal and ASA as antithrombotic agents.", "contents": "Comparison of the inhibitory effects of acetylsalicylic acid and trifusal on enzymes related to thrombosis. Triflusal is a new antithrombotic agent, structurally similar to acetylsalicylic acid (ASA), which has been shown to possess a different pharmacological profile, suggesting a different mechanism of action for both compounds. To confirm this hypothesis we have studied, comparatively, the inhibition by  triflusal and ASA of the activity of several enzymes involved in the equilibrium of platelet haemostasis, namely, prostaglandin-synthetase system (PG-synthetase), cyclo-oxygenase, thromboxane-synthetase and cAMP-phosphodiesterase. Results indicate that trilfusal is 60% less potent as inhibitor of cyclooxygenase (biological method) and of prostaglandin biosynthesis (spectrophotometric method ) than ASA. On the contrary, triflusal is five times more potent than ASA as inhibitor of cAMP phosphodoesterase. Inhibition of thromboxane-synthetase by both compounds is negligible and without physiological significance. These results suggest a mechanism of action of trifusal that might explain the different pharmacological profile between triflusal and ASA as antithrombotic agents."}
{"id": "PMID:226022", "title": "Hypocalcemia. Differential diagnosis and mechanisms.", "content": "There is much individual variability in the clinical manifestations of hypocalcemia. The rapidly of the development of hypocalcemia will determine whether or not symptoms will be present. Signs and symptoms of hypocalcemia consisted of tetany (Chvostek's and Trousseau's signs), seizures, diminshed to absent deep tendon reflexes, papilledema, mental changes (weakness, fatigue, irritability, memory loss, confusion, delusion, hallucination), and skin changes. Etiologic factors for hypocalcemia in man include (1) decreased calcium absorption or increased loss from the gastrointestinal tract; (2) parathyroid hormone deficiency; (3) skeletal resistance to parathyroid hormone; (4) ineffective parathyroid hormone; (5) decreased production or increased degradation of 25-hydroxycholecalciferol or 1,25-dihydroxycholecalciferol; (6) increased complex formation with calcium; (7) increased skeletal uptake of calcium; (8) hypomagnesemic state; and (9) direct inhibition of bone resorption. Measurement of total and ionic calcium, magnesium, parathyroid hormone, vitamin D metabolites (25-hydroxycholecalciferol, 1,25-dihydroxycholecalciferol), and nephrogenous cyclic adenosine monophosphate are especially helpful in the laboratory evaluation of the hypocalcemic patient.", "contents": "Hypocalcemia. Differential diagnosis and mechanisms. There is much individual variability in the clinical manifestations of hypocalcemia. The rapidly of the development of hypocalcemia will determine whether or not symptoms will be present. Signs and symptoms of hypocalcemia consisted of tetany (Chvostek's and Trousseau's signs), seizures, diminshed to absent deep tendon reflexes, papilledema, mental changes (weakness, fatigue, irritability, memory loss, confusion, delusion, hallucination), and skin changes. Etiologic factors for hypocalcemia in man include (1) decreased calcium absorption or increased loss from the gastrointestinal tract; (2) parathyroid hormone deficiency; (3) skeletal resistance to parathyroid hormone; (4) ineffective parathyroid hormone; (5) decreased production or increased degradation of 25-hydroxycholecalciferol or 1,25-dihydroxycholecalciferol; (6) increased complex formation with calcium; (7) increased skeletal uptake of calcium; (8) hypomagnesemic state; and (9) direct inhibition of bone resorption. Measurement of total and ionic calcium, magnesium, parathyroid hormone, vitamin D metabolites (25-hydroxycholecalciferol, 1,25-dihydroxycholecalciferol), and nephrogenous cyclic adenosine monophosphate are especially helpful in the laboratory evaluation of the hypocalcemic patient."}
{"id": "PMID:226023", "title": "[Congenital cardiopathies in a tropical environment. Study of 259 cases seen at Abidjan from 1969-1976].", "content": "The authors report the study of 259 cases of congenital heart disease observed at Abidjan between 1969-1976. The average age of the patients was 7-8 years ranging from the newborn to 41 years. The principal malformations encountered in their order of frequency were: ventricular septal defect 38.6 p. 100, atrial septal defect 13.8 p. 100, Fallot's tetralogy 8.8 p. 100, pulmonary stenosis 8.1 100, patent ductus arteriosus 7.7 p. 100, atrioventricular canal 7.7 p. 100, transposition of the great arteries 3.8 p. 100, coarctation of the aorta 2.3 p. 100. There were associated malformations in 31 cases. 42 patients were catheterised at Abidjan, 28 were operated, 12 at Abidjan. These statistics are compared to those already reported of congenital heart disease in tropical and western countries. There is little difference in the distribution of the various cardiac malformations. Two congenital malformations appear to be less frequent in the Tropics: coarctation of the aorta and aortic stenosis.", "contents": "[Congenital cardiopathies in a tropical environment. Study of 259 cases seen at Abidjan from 1969-1976]. The authors report the study of 259 cases of congenital heart disease observed at Abidjan between 1969-1976. The average age of the patients was 7-8 years ranging from the newborn to 41 years. The principal malformations encountered in their order of frequency were: ventricular septal defect 38.6 p. 100, atrial septal defect 13.8 p. 100, Fallot's tetralogy 8.8 p. 100, pulmonary stenosis 8.1 100, patent ductus arteriosus 7.7 p. 100, atrioventricular canal 7.7 p. 100, transposition of the great arteries 3.8 p. 100, coarctation of the aorta 2.3 p. 100. There were associated malformations in 31 cases. 42 patients were catheterised at Abidjan, 28 were operated, 12 at Abidjan. These statistics are compared to those already reported of congenital heart disease in tropical and western countries. There is little difference in the distribution of the various cardiac malformations. Two congenital malformations appear to be less frequent in the Tropics: coarctation of the aorta and aortic stenosis."}
{"id": "PMID:226024", "title": "[Study of the renin-angiotensin system in 2 cases of Wilm's tumor with severe arterial hypertension].", "content": "Two children who presented with Wilm's tumour and severe hypertension are described. The hypertension, which was secondary to excessive renin secretion, regressed after unilateral nephrectomy. In one child the total quantity of renin in the tumour was high and the peripheral plasma renin was also increased. The latter was unaffected by posture or a low salt diet and on angiography there was no compression of the renal arteries. Electron microscopy of the tumour cells showed numerous intra-cytoplasmic granules. In the other child the peripheral renin was only moderated elevated and could be stimulated by changes in posture or a low salt diet. Angiography demonstrated a large tumour that was compressing the renal artery on that side. No renin was detected in the tumour. In this child the inappropriate secretion of renin was probably due to renal parenchyma close to the tumour causing reno-vascular hypertension. The anti-hypertensive effect of propranolol given pre-operatively was excellent.", "contents": "[Study of the renin-angiotensin system in 2 cases of Wilm's tumor with severe arterial hypertension]. Two children who presented with Wilm's tumour and severe hypertension are described. The hypertension, which was secondary to excessive renin secretion, regressed after unilateral nephrectomy. In one child the total quantity of renin in the tumour was high and the peripheral plasma renin was also increased. The latter was unaffected by posture or a low salt diet and on angiography there was no compression of the renal arteries. Electron microscopy of the tumour cells showed numerous intra-cytoplasmic granules. In the other child the peripheral renin was only moderated elevated and could be stimulated by changes in posture or a low salt diet. Angiography demonstrated a large tumour that was compressing the renal artery on that side. No renin was detected in the tumour. In this child the inappropriate secretion of renin was probably due to renal parenchyma close to the tumour causing reno-vascular hypertension. The anti-hypertensive effect of propranolol given pre-operatively was excellent."}
{"id": "PMID:226026", "title": "Plasma cells with inclusions containing iron.", "content": "Iron inclusions in plasma cells of the bone marrow of an individual suffering from megaloblastic anemia due to folate deficiency were examined by electron microscopy. It seems that the iron is introduced into the plasma cell by micropinocytosis. The speculation of possible transfer of iron from the reticulum macrophage to the plasma cell is raised.", "contents": "Plasma cells with inclusions containing iron. Iron inclusions in plasma cells of the bone marrow of an individual suffering from megaloblastic anemia due to folate deficiency were examined by electron microscopy. It seems that the iron is introduced into the plasma cell by micropinocytosis. The speculation of possible transfer of iron from the reticulum macrophage to the plasma cell is raised."}
{"id": "PMID:226027", "title": "Isoantigens A, B, H in normal skin and tumors of the epidermal appendages.", "content": "Isoantigens A, B, H(O) in biopsy specimens of 26 normal skin and in 35 adnexal tumors were studied by the red cell adherence (RCA) test of Davidsohn. Isoantigens were detected in the stratum corneum, stratum granulosum, stratum spinosum, acrosyringium, keratogenous zone of hair follicle, eccrine duct, and eccrine gland. The apocrine gland and duct consistently had negative test results for isoantigens. Seventy percent of all tumors tested contained isoantigens and included syringoma, hidrocystoma, syringocystadenoma papilliferum, spiradenoma, eccrine poroma, dermal duct tumor, clear cell hidradenoma, and cylindroma. We interpreted the presence of isoantigens in adnexal tumors as being evidence of immunologic maturity with differentiation toward eccrine structures. The RCA test is a new, sensitive, immunologic technique that can complement enzyme histochemical stains and electron microscopy in the study of the histogenesis of adnexal skin tumors.", "contents": "Isoantigens A, B, H in normal skin and tumors of the epidermal appendages. Isoantigens A, B, H(O) in biopsy specimens of 26 normal skin and in 35 adnexal tumors were studied by the red cell adherence (RCA) test of Davidsohn. Isoantigens were detected in the stratum corneum, stratum granulosum, stratum spinosum, acrosyringium, keratogenous zone of hair follicle, eccrine duct, and eccrine gland. The apocrine gland and duct consistently had negative test results for isoantigens. Seventy percent of all tumors tested contained isoantigens and included syringoma, hidrocystoma, syringocystadenoma papilliferum, spiradenoma, eccrine poroma, dermal duct tumor, clear cell hidradenoma, and cylindroma. We interpreted the presence of isoantigens in adnexal tumors as being evidence of immunologic maturity with differentiation toward eccrine structures. The RCA test is a new, sensitive, immunologic technique that can complement enzyme histochemical stains and electron microscopy in the study of the histogenesis of adnexal skin tumors."}
{"id": "PMID:226028", "title": "Membranous nephropathy. Its association with multicentric angiofollicular lymph node hyperplasia.", "content": "Multicentric angiofollicular lymph node hyperplasia of the plasma cell type with systemic manifestations developed in a 51-year-old man. One year later, the nephrotic syndrome due to typical immune complex mediated membranous nephropathy developed. Elevated titers to Epstein-Barr viral antigens suggesting reactivation of a latent infection were present. The patient has required conservative medical management only. The association of membranous nephropathy with angiofollicular lymph node hyperplasia lends further evidence to the postulate that the disorder is a manifestation of chronic immune stimulation by a foreign antigen.", "contents": "Membranous nephropathy. Its association with multicentric angiofollicular lymph node hyperplasia. Multicentric angiofollicular lymph node hyperplasia of the plasma cell type with systemic manifestations developed in a 51-year-old man. One year later, the nephrotic syndrome due to typical immune complex mediated membranous nephropathy developed. Elevated titers to Epstein-Barr viral antigens suggesting reactivation of a latent infection were present. The patient has required conservative medical management only. The association of membranous nephropathy with angiofollicular lymph node hyperplasia lends further evidence to the postulate that the disorder is a manifestation of chronic immune stimulation by a foreign antigen."}
{"id": "PMID:226030", "title": "Differentiation of vaccine strains and field isolates of pseudorabies (Aujeszky's disease) virus: thermal sensitivity and rabbit virulence markers.", "content": "Eleven cloned North American pseudorabies virus (PRV) strains and the European vaccine strains K and BUK were characterized by their thermal sensitivity and rabbit virulence markers. Heat sensitivity of the strains and isolates ranged from the highly heat resistant strain K, to the extremely heat labile strain BUK and isolate Be. The inactivation curves of each virus were transformed to the logarithmic scale and their standardized slopes and predicted virus survival values at 30 minutes were plotted against each other. The result was a distribution of points that represented a thermal sensitivity spectrum (TSS). Virus strains were subsequently categorized into 1 of 3 groups according to their position in the TSS. Viruses were also categorized into three groups according to their ability to clinically infect rabbits, their ability to produce pruritus and the time required to kill. When individual strains were described according to their marker profiles, 5 of 9 possible marker combinations were revealed. The 2 vaccine strains were each described by separate profiles. Virulent field isolates were characterized by 1 of 3 different profiles.", "contents": "Differentiation of vaccine strains and field isolates of pseudorabies (Aujeszky's disease) virus: thermal sensitivity and rabbit virulence markers. Eleven cloned North American pseudorabies virus (PRV) strains and the European vaccine strains K and BUK were characterized by their thermal sensitivity and rabbit virulence markers. Heat sensitivity of the strains and isolates ranged from the highly heat resistant strain K, to the extremely heat labile strain BUK and isolate Be. The inactivation curves of each virus were transformed to the logarithmic scale and their standardized slopes and predicted virus survival values at 30 minutes were plotted against each other. The result was a distribution of points that represented a thermal sensitivity spectrum (TSS). Virus strains were subsequently categorized into 1 of 3 groups according to their position in the TSS. Viruses were also categorized into three groups according to their ability to clinically infect rabbits, their ability to produce pruritus and the time required to kill. When individual strains were described according to their marker profiles, 5 of 9 possible marker combinations were revealed. The 2 vaccine strains were each described by separate profiles. Virulent field isolates were characterized by 1 of 3 different profiles."}
{"id": "PMID:226031", "title": "Colostral immunity in piglets from sows vaccinated with inactivated Aujeszky disease virus vaccine.", "content": "Neutralizing antibodies against ADV were transmitted from sows, vaccinated with inactivated ADV adjuvanted with DEAE dextran, to their offspring via colostrum. The suckling piglets were protected by colostral immunity against contact infection with ADV at week 1 p.p., however, they were not protected against i.n. infection (10(8) TCD50). At 2 and 3 weeks p.p. all the piglets were protected against both contact infection and i.n. infection. At 4 weeks p.p. 50 per cent of the litter were protected against i.n. infection, in spite of very low antibody titres (1:2--1:4). The colostral antibodies did not interfere with active antibody response when the piglets were vaccinated with the inactivated vaccine from 2 weeks p.p. onward. Lymphocytes from suckling piglets of a vaccinated sow showed in vitro reactivity (enhanced 3H-thymidine incorporation) against ADV and BHK antigen, both contained in the vaccine used for the immunization of the sow.", "contents": "Colostral immunity in piglets from sows vaccinated with inactivated Aujeszky disease virus vaccine. Neutralizing antibodies against ADV were transmitted from sows, vaccinated with inactivated ADV adjuvanted with DEAE dextran, to their offspring via colostrum. The suckling piglets were protected by colostral immunity against contact infection with ADV at week 1 p.p., however, they were not protected against i.n. infection (10(8) TCD50). At 2 and 3 weeks p.p. all the piglets were protected against both contact infection and i.n. infection. At 4 weeks p.p. 50 per cent of the litter were protected against i.n. infection, in spite of very low antibody titres (1:2--1:4). The colostral antibodies did not interfere with active antibody response when the piglets were vaccinated with the inactivated vaccine from 2 weeks p.p. onward. Lymphocytes from suckling piglets of a vaccinated sow showed in vitro reactivity (enhanced 3H-thymidine incorporation) against ADV and BHK antigen, both contained in the vaccine used for the immunization of the sow."}
{"id": "PMID:226032", "title": "Biological properties of mouse interferon bound to a high molecular weight carrier: Blue Dextran 2000.", "content": "Mouse C-243 cell interferon (IF) binds to Blue Dextran 2000 (BD). The BD-IF complex could be precipitated by polyethylene glycol. When 0.05 to 0.2 per cent solutions of BD were used for binding IF, the recovery of IF activity in the sediment was complete. The BD-IF complex was shown to have high antiviral activity, it was stable for months at 4 degrees C but it was inactivated by heating at 37 degrees, 56 degrees and 65 degrees C as native IF. The rate of clearance of IF bound to BD from the mouse peritoneal cavity was found to be significantly slower than that of native IF. The BD-IF complex was highly immunogenic for rabbits and sheep. Furthermore, the BD-IF complex was neutralized to a greater extent by specific antibodies than native IF.", "contents": "Biological properties of mouse interferon bound to a high molecular weight carrier: Blue Dextran 2000. Mouse C-243 cell interferon (IF) binds to Blue Dextran 2000 (BD). The BD-IF complex could be precipitated by polyethylene glycol. When 0.05 to 0.2 per cent solutions of BD were used for binding IF, the recovery of IF activity in the sediment was complete. The BD-IF complex was shown to have high antiviral activity, it was stable for months at 4 degrees C but it was inactivated by heating at 37 degrees, 56 degrees and 65 degrees C as native IF. The rate of clearance of IF bound to BD from the mouse peritoneal cavity was found to be significantly slower than that of native IF. The BD-IF complex was highly immunogenic for rabbits and sheep. Furthermore, the BD-IF complex was neutralized to a greater extent by specific antibodies than native IF."}
{"id": "PMID:226033", "title": "Latent infection of cattle with bovid herpesvirus 2.", "content": "In a series of experiments, 10 calves were infected by different routes with bovine mammillitis strain of bovid herpesvirus 2 (BHV2). Nine of the calves developed lesions and BHV2 was isolated from 8 calves. At intervals, after clinical recovery, the calves were given a course of corticosteroid by intravenous injection. Subsequently 7 calves developed lesions and from 3 calves BHV2 was reisolated. The shortest interval between initial infection and reisolation of virus was 10 weeks. In one calf virus was recovered on 3 occasions, at intervals of 20, 44 and 74 weeks post-infection. It is probable that BHV2 can occur as a latent infection in calves and that BHV2 should be included among the herpesviruses known to remain latent.", "contents": "Latent infection of cattle with bovid herpesvirus 2. In a series of experiments, 10 calves were infected by different routes with bovine mammillitis strain of bovid herpesvirus 2 (BHV2). Nine of the calves developed lesions and BHV2 was isolated from 8 calves. At intervals, after clinical recovery, the calves were given a course of corticosteroid by intravenous injection. Subsequently 7 calves developed lesions and from 3 calves BHV2 was reisolated. The shortest interval between initial infection and reisolation of virus was 10 weeks. In one calf virus was recovered on 3 occasions, at intervals of 20, 44 and 74 weeks post-infection. It is probable that BHV2 can occur as a latent infection in calves and that BHV2 should be included among the herpesviruses known to remain latent."}
{"id": "PMID:226034", "title": "Studies on avian infectious bronchitis virus (IBV). II. Propagation of IBV in several cultured cells.", "content": "The growth of ten strains of avian infectious bronchitis virus (IBV) in several cultured cells was examined. The cultured cells used were chick kidney (CK), chick embryo (CE), HeLa and BHK-21 cells. The results obtained can be summarized as follows. 1. All the strains showed similar growth curves in CK cells. Progeny viruses appeared in the culture medium 4 to 6 hours after inoculation and peak virus titers of 10(6.5)--10(8.5) TCID50 per 0.1 ml were obtained after 36 hours. A cytopathogenic effect (CPE) was detected within 24 hours. No distinct CPE and low multiplicities were observed on culturing at 30 degrees C. 2. All strains replicated in CE cells, although only small amounts of virus were produced. No CPE was observed. 3. Only Beaudette-42 and Holte strains grew in BHK-21 cells. 4. No IBV strains grew in HeLa cells.", "contents": "Studies on avian infectious bronchitis virus (IBV). II. Propagation of IBV in several cultured cells. The growth of ten strains of avian infectious bronchitis virus (IBV) in several cultured cells was examined. The cultured cells used were chick kidney (CK), chick embryo (CE), HeLa and BHK-21 cells. The results obtained can be summarized as follows. 1. All the strains showed similar growth curves in CK cells. Progeny viruses appeared in the culture medium 4 to 6 hours after inoculation and peak virus titers of 10(6.5)--10(8.5) TCID50 per 0.1 ml were obtained after 36 hours. A cytopathogenic effect (CPE) was detected within 24 hours. No distinct CPE and low multiplicities were observed on culturing at 30 degrees C. 2. All strains replicated in CE cells, although only small amounts of virus were produced. No CPE was observed. 3. Only Beaudette-42 and Holte strains grew in BHK-21 cells. 4. No IBV strains grew in HeLa cells."}
{"id": "PMID:226036", "title": "Virus isolation and serum antibody responses after infection of cats with transmissible gastroenteritis virus. Brief report.", "content": "Transmissible gastroenteritis virus was administered orally to cats. No clinical disease resulted but infectious virus was isolated from faeces for up to 22 days after infection and serum antibody was detected by neutralisation and immunofluorescence tests.", "contents": "Virus isolation and serum antibody responses after infection of cats with transmissible gastroenteritis virus. Brief report. Transmissible gastroenteritis virus was administered orally to cats. No clinical disease resulted but infectious virus was isolated from faeces for up to 22 days after infection and serum antibody was detected by neutralisation and immunofluorescence tests."}
{"id": "PMID:226037", "title": "Possible pitfalls in the study of IgG receptors produced by herpesvirus-infected cells. Brief report.", "content": "The presence of specific antibodies to human herpesviruses in certain purified human IgG preparations from commercial sources may produce misleading results when such preparations are used in studied on the IgG receptors produced by virus-infected cells.", "contents": "Possible pitfalls in the study of IgG receptors produced by herpesvirus-infected cells. Brief report. The presence of specific antibodies to human herpesviruses in certain purified human IgG preparations from commercial sources may produce misleading results when such preparations are used in studied on the IgG receptors produced by virus-infected cells."}
{"id": "PMID:226038", "title": "Isolation of an adeno associated virus from sheep. Brief report.", "content": "An adenovirus and a spherical virus 20--24 nm diameter were isolated from ovine faeces. The small virus replicated in the nucleus, and was associated especially with the nucleolus. It haemagglutinated guinea pig and human erythrocytes, was thermostable and required an adenovirus for replication. It is concluded that this represents the first recorded isolate of an ovine AAV.", "contents": "Isolation of an adeno associated virus from sheep. Brief report. An adenovirus and a spherical virus 20--24 nm diameter were isolated from ovine faeces. The small virus replicated in the nucleus, and was associated especially with the nucleolus. It haemagglutinated guinea pig and human erythrocytes, was thermostable and required an adenovirus for replication. It is concluded that this represents the first recorded isolate of an ovine AAV."}
{"id": "PMID:226040", "title": "[HBS Ag-positive hepatocellular cancer (pathomorphologic study)].", "content": "Pathomophological and histochemical analysis of 7 autopsy cases of primary hepatocellular carcinoma was performed. Direct immunofluorescence with an anti-HBsAg serum and staining with orsein according to Shikata's method revealed the presence of HBsAg in hepatocytes of the cirrhotic tissue and in tumour cells. Cirrhotic nodes were found to have numerous HBsAg-positive cells, whereas in the tumour tissue the number of such cells was insignificant and they were found only in highly differentiated areas. In all cases, highly differentiated hepatocellular carcinoma was combined with active large nodular cirrhosis.", "contents": "[HBS Ag-positive hepatocellular cancer (pathomorphologic study)]. Pathomophological and histochemical analysis of 7 autopsy cases of primary hepatocellular carcinoma was performed. Direct immunofluorescence with an anti-HBsAg serum and staining with orsein according to Shikata's method revealed the presence of HBsAg in hepatocytes of the cirrhotic tissue and in tumour cells. Cirrhotic nodes were found to have numerous HBsAg-positive cells, whereas in the tumour tissue the number of such cells was insignificant and they were found only in highly differentiated areas. In all cases, highly differentiated hepatocellular carcinoma was combined with active large nodular cirrhosis."}
{"id": "PMID:226041", "title": "Nuclear bodies in nerve cells of two patients with normal-pressure hydrocephalus.", "content": "Biopsy specimen fragments from two patients with normal-pressure hydrocephalus were studied using ultrastructural methods. Simple nuclear bodies were found in all layers of the cortex and white matter, whereas complex ones were only seen in the fifth and sixth layers and in the underlying white matter. There may be a relationship of these nuclear bodies, either to the neuroglial proliferation observed in both patients or to the existence of a viral infection of the CNS.", "contents": "Nuclear bodies in nerve cells of two patients with normal-pressure hydrocephalus. Biopsy specimen fragments from two patients with normal-pressure hydrocephalus were studied using ultrastructural methods. Simple nuclear bodies were found in all layers of the cortex and white matter, whereas complex ones were only seen in the fifth and sixth layers and in the underlying white matter. There may be a relationship of these nuclear bodies, either to the neuroglial proliferation observed in both patients or to the existence of a viral infection of the CNS."}
{"id": "PMID:226043", "title": "Ocular manifestations of familial high-density lipoprotein deficiency (Tangier disease).", "content": "Corneal clouding is one of the manifestations of Tangier disease, an inherited disorder in which cholesterol-rich lipids are deposited in various tissues of the body. The cause of the corneal clouding is unknown. This study documents the clinical course and conjunctival biopsy findings of a 60-year-old man who was one of the earliest patients to be recognized with Tangier disease and in whom progressive corneal clouding developed in adult life. Noteworthy in the biopsy specimens were birefringent lipid particles that were predominantly present in degenerating pericytes of the conjunctival vessels.", "contents": "Ocular manifestations of familial high-density lipoprotein deficiency (Tangier disease). Corneal clouding is one of the manifestations of Tangier disease, an inherited disorder in which cholesterol-rich lipids are deposited in various tissues of the body. The cause of the corneal clouding is unknown. This study documents the clinical course and conjunctival biopsy findings of a 60-year-old man who was one of the earliest patients to be recognized with Tangier disease and in whom progressive corneal clouding developed in adult life. Noteworthy in the biopsy specimens were birefringent lipid particles that were predominantly present in degenerating pericytes of the conjunctival vessels."}
{"id": "PMID:226045", "title": "Isolation of an aminoglycoside receptor from guinea pig inner ear tissues and kidney.", "content": "Affinity chromatography was used to isolate aminoglycoside receptors from inner ear tissues and kidney. Neomycin was immobilized on glass beads and served as the stationary phase in column chromatography. Fractionation of an organic tissue extract on this matrix demonstrated two components with high affinity for neomycin: phohphatidyl inositol phosphate and phosphatidyl inositol diphosphate. The toxicity of aminoglycosides is explained on the basis of a drug-interaction with these lipids.", "contents": "Isolation of an aminoglycoside receptor from guinea pig inner ear tissues and kidney. Affinity chromatography was used to isolate aminoglycoside receptors from inner ear tissues and kidney. Neomycin was immobilized on glass beads and served as the stationary phase in column chromatography. Fractionation of an organic tissue extract on this matrix demonstrated two components with high affinity for neomycin: phohphatidyl inositol phosphate and phosphatidyl inositol diphosphate. The toxicity of aminoglycosides is explained on the basis of a drug-interaction with these lipids."}
{"id": "PMID:226046", "title": "Noradrenergic transmission in isolated guinea-pig intestine following in vivo administration of antibodies to dopamine beta-hydroxylase.", "content": "The effectiveness of transmission from noradrenergic nerves supplying the guinea-pig ileum was evaluated in normal preparations and in preparations taken from animals injected 18 h to 4 days previously with antiserum to dopamine beta-hydroxylase. Degeneration of the nerves following the antiserum was monitored histochemically in the same preparations. A decline in the effectiveness of transmission, which paralleled the degeneration of the nerves, was observed. The earliest effects were detected at 18 h and the greatest effect was found at 2-4 days following the administration of antiserum. Binding of the antibodies has been detected as early as 6 h after injection. It is therefore concluded that binding of the antibodies to the nerves, per se, does not significantly compromise transmission, and that histochemical evidence of degeneration can be used to indicate the onset of functional deterioration of noradrenergic nerves following their exposure to antibodies to dopamine beta-hydroxylase.", "contents": "Noradrenergic transmission in isolated guinea-pig intestine following in vivo administration of antibodies to dopamine beta-hydroxylase. The effectiveness of transmission from noradrenergic nerves supplying the guinea-pig ileum was evaluated in normal preparations and in preparations taken from animals injected 18 h to 4 days previously with antiserum to dopamine beta-hydroxylase. Degeneration of the nerves following the antiserum was monitored histochemically in the same preparations. A decline in the effectiveness of transmission, which paralleled the degeneration of the nerves, was observed. The earliest effects were detected at 18 h and the greatest effect was found at 2-4 days following the administration of antiserum. Binding of the antibodies has been detected as early as 6 h after injection. It is therefore concluded that binding of the antibodies to the nerves, per se, does not significantly compromise transmission, and that histochemical evidence of degeneration can be used to indicate the onset of functional deterioration of noradrenergic nerves following their exposure to antibodies to dopamine beta-hydroxylase."}
{"id": "PMID:226048", "title": "Infectious bursal disease viral infections. II. The relationship of age, complement levels, virus-neutralizing antibody, clotting, and lesions.", "content": "Experimental infection with infectious bursal disease virus (IBDV) reduced the complement (C) titer in 8-week-old chickens on days 3, 5, and 7 postinfection. Since the C titer was much lower in normal 2-week-old chickens than in normal 8-week-old chickens it could not be determined whether there was a reduction in titer during the infection process. Virus-neutralizing antibody rose rapidly following infection in both 2- and 8-week-old chickens. Hyper-immune serum given during infection in an attempt to produce immune complexes did not increase disease severity in either 2- or 6-week-old susceptible chickens.", "contents": "Infectious bursal disease viral infections. II. The relationship of age, complement levels, virus-neutralizing antibody, clotting, and lesions. Experimental infection with infectious bursal disease virus (IBDV) reduced the complement (C) titer in 8-week-old chickens on days 3, 5, and 7 postinfection. Since the C titer was much lower in normal 2-week-old chickens than in normal 8-week-old chickens it could not be determined whether there was a reduction in titer during the infection process. Virus-neutralizing antibody rose rapidly following infection in both 2- and 8-week-old chickens. Hyper-immune serum given during infection in an attempt to produce immune complexes did not increase disease severity in either 2- or 6-week-old susceptible chickens."}
{"id": "PMID:226049", "title": "Effects of avian reovirus on Marek's disease (MD). I. Suppression of MD development.", "content": "The effects of an avian reovirus on the development of acute Marek's disease (MD) were studied by exposing chickens to Reo-W isolant of avian reovirus before infecting them with an oncogenic MD herpesvirus (MDHV). Four separate trials were made in a similar manner, 2 trials with an experimental line of White Leghorn (WSU-VS) highly susceptible to MD, and 2 trials with a commercial strain of meat-type (C-MT) chicken. MD mortality and/or incidence of gross MD lesions were consistently reduced by preexposure to avian reovirus. The suppression was more apparent in the WSU-VS than in the C-MT birds, and appeared greater with exposure to reovirus via the respiratory route than with the alimentary route.", "contents": "Effects of avian reovirus on Marek's disease (MD). I. Suppression of MD development. The effects of an avian reovirus on the development of acute Marek's disease (MD) were studied by exposing chickens to Reo-W isolant of avian reovirus before infecting them with an oncogenic MD herpesvirus (MDHV). Four separate trials were made in a similar manner, 2 trials with an experimental line of White Leghorn (WSU-VS) highly susceptible to MD, and 2 trials with a commercial strain of meat-type (C-MT) chicken. MD mortality and/or incidence of gross MD lesions were consistently reduced by preexposure to avian reovirus. The suppression was more apparent in the WSU-VS than in the C-MT birds, and appeared greater with exposure to reovirus via the respiratory route than with the alimentary route."}
{"id": "PMID:226050", "title": "Growth kinetics of embryo- and organ-culture adapted Beaudette strain of infectious bronchitis virus in embryonated chicken eggs.", "content": "Three Beaudette strains of infectious bronchitis virus (IBV) [two chicken-embryo trachea-culture-adapted (E71CET10 and E71CEK10CET30) and one embryo-adapted (E72)] were propagated in 10-day-old embryonated chicken eggs (CE) to investigate growth and lethality patterns. The E72 and E71CEK10CET30 viruses were similar in growth pattern as to logarithmic phase and maximum virus production, but 95% of the CE mortality with E72 virus occurred between 20 and 32 hours whereas with E71CEK10CET30 60% mortality occurred between 36 and 84 hours. The yield of the E71CET10 virus was minimum, with little lethality.", "contents": "Growth kinetics of embryo- and organ-culture adapted Beaudette strain of infectious bronchitis virus in embryonated chicken eggs. Three Beaudette strains of infectious bronchitis virus (IBV) [two chicken-embryo trachea-culture-adapted (E71CET10 and E71CEK10CET30) and one embryo-adapted (E72)] were propagated in 10-day-old embryonated chicken eggs (CE) to investigate growth and lethality patterns. The E72 and E71CEK10CET30 viruses were similar in growth pattern as to logarithmic phase and maximum virus production, but 95% of the CE mortality with E72 virus occurred between 20 and 32 hours whereas with E71CEK10CET30 60% mortality occurred between 36 and 84 hours. The yield of the E71CET10 virus was minimum, with little lethality."}
{"id": "PMID:226051", "title": "Transmission of acute respiratory disease (rhinotracheitis) of turkeys.", "content": "Clinical signs of acute respiratory disease of turkeys were transmitted to susceptible day-old poults by direct contact, litter contact, and drinking water. Attempts failed to transmit the disease by air (cage-to-cage) or by oral and nasal inoculation with feces, nasal exudates, or nasal turbinate extracts. The disease was not transmitted by inoculation with white blood cells. Chicks were not affected by the disease, but young quail developed signs of respiratory disease when exposed to contaminated drinking water. Thus, acute respiratory disease in turkeys appears to be of an infectious nature, and the infectious agent(s) probably exist in the heavily contaminated environment used to house young commercial turkey poults.", "contents": "Transmission of acute respiratory disease (rhinotracheitis) of turkeys. Clinical signs of acute respiratory disease of turkeys were transmitted to susceptible day-old poults by direct contact, litter contact, and drinking water. Attempts failed to transmit the disease by air (cage-to-cage) or by oral and nasal inoculation with feces, nasal exudates, or nasal turbinate extracts. The disease was not transmitted by inoculation with white blood cells. Chicks were not affected by the disease, but young quail developed signs of respiratory disease when exposed to contaminated drinking water. Thus, acute respiratory disease in turkeys appears to be of an infectious nature, and the infectious agent(s) probably exist in the heavily contaminated environment used to house young commercial turkey poults."}
{"id": "PMID:226052", "title": "Growth of infectious bursal disease virus with plaque formation in chick embryo fibroblast cell culture.", "content": "The WA69 isolant of infectious bursal disease virus (IBDV) induced cytopathic effects and plaque formation in chick embryo fibroblast (CEF) cultures after serial passages in embryonated eggs and then in CEF cultures. The plaque-forming agent was cloned (designated WA69 clone) and identified as IBDV on the basis of serologic response in inoculated birds and its antigenic relationship to other known IBDV isolants. The WA69 clone replicated rapidly in CEF cultures, reaching peak titers at 48 hours postinoculation, and the virus caused only minimal histologic lesions of the bursa when inoculated into 3-week-old chicks from a specific-pathogen-free flock. The growth of IBDV in CEF cultures with plaque formation may provide a simple in vitro system for virological and serological studies of IBDV.", "contents": "Growth of infectious bursal disease virus with plaque formation in chick embryo fibroblast cell culture. The WA69 isolant of infectious bursal disease virus (IBDV) induced cytopathic effects and plaque formation in chick embryo fibroblast (CEF) cultures after serial passages in embryonated eggs and then in CEF cultures. The plaque-forming agent was cloned (designated WA69 clone) and identified as IBDV on the basis of serologic response in inoculated birds and its antigenic relationship to other known IBDV isolants. The WA69 clone replicated rapidly in CEF cultures, reaching peak titers at 48 hours postinoculation, and the virus caused only minimal histologic lesions of the bursa when inoculated into 3-week-old chicks from a specific-pathogen-free flock. The growth of IBDV in CEF cultures with plaque formation may provide a simple in vitro system for virological and serological studies of IBDV."}
{"id": "PMID:226053", "title": "Immune-complex involvement in the pathogenesis of infectious bursal disease virus in chickens.", "content": "Frozen kidney sections from chickens inoculated with infectious bursal disease virus (IBDV) were stained with fluorescein-conjugated rabbit anti-chicken gamma-globulin. Fluorescence was observed in the renal glomeruli of infected chickens, indicating that gamma-globulins, probably in the form of immune complexes, had lodged in the glomeruli of IBDV-infected chickens. This suggests that immune complexes may play an important role in the pathogenesis of IBDV infections in chickens.", "contents": "Immune-complex involvement in the pathogenesis of infectious bursal disease virus in chickens. Frozen kidney sections from chickens inoculated with infectious bursal disease virus (IBDV) were stained with fluorescein-conjugated rabbit anti-chicken gamma-globulin. Fluorescence was observed in the renal glomeruli of infected chickens, indicating that gamma-globulins, probably in the form of immune complexes, had lodged in the glomeruli of IBDV-infected chickens. This suggests that immune complexes may play an important role in the pathogenesis of IBDV infections in chickens."}
{"id": "PMID:226057", "title": "Vigilance performance of men sleeping under arctic conditions.", "content": "This study investigated the effect of cold exposure on vigilance performance in men working and sleeping under Arctic conditions. The results were compared with changes in the amount of REM sleep. EEG sleep recordings were made on six subjects during five baseline nights in laboratory conditions, 16 experimental nights in Arctic conditions, and four recovery nights in the laboratory. Vigilance tests were administered every second day during the experimental period and two times during each of the baseline and recovery periods. During the first night in the Arctic, the amount of REM sleep fell to 50% of baseline and a large decrement occurred in detection performance on the following morning. During the remaining nights in the cold, REM deprivation averaged about 25% with somewhat greater deprivation occurring during colder nights. Reaction time measures generally increased throughout the experimental period and subsequently showed incomplete recovery. However, detection performance gradually improved during the experimental period but showed some regression following colder-than-usual nights, when REM deprivation increased. This suggested that performance on this type of task may be related to temperature variations and changes in REM deprivation.", "contents": "Vigilance performance of men sleeping under arctic conditions. This study investigated the effect of cold exposure on vigilance performance in men working and sleeping under Arctic conditions. The results were compared with changes in the amount of REM sleep. EEG sleep recordings were made on six subjects during five baseline nights in laboratory conditions, 16 experimental nights in Arctic conditions, and four recovery nights in the laboratory. Vigilance tests were administered every second day during the experimental period and two times during each of the baseline and recovery periods. During the first night in the Arctic, the amount of REM sleep fell to 50% of baseline and a large decrement occurred in detection performance on the following morning. During the remaining nights in the cold, REM deprivation averaged about 25% with somewhat greater deprivation occurring during colder nights. Reaction time measures generally increased throughout the experimental period and subsequently showed incomplete recovery. However, detection performance gradually improved during the experimental period but showed some regression following colder-than-usual nights, when REM deprivation increased. This suggested that performance on this type of task may be related to temperature variations and changes in REM deprivation."}
{"id": "PMID:226054", "title": "Complement-dependent antibody cytotoxicity test of chicken antibody with duck complement used against cells of a Marek's disease lymphoma-derived cell line (MSB-1).", "content": "Complement-dependent antibody cytotoxicity (CDAC) against cells of a lymphoblastoid cell line (MSB-1) derived from Marek's disease lymphoma was investigated in a chicken antibody system using complements from several animal species. Cytotoxicity was seldom observed when rabbit, guinea pig, or chicken complements were used in the presence of hyperimmune chicken serum against MSB-1. With duck complement, however, cytotoxicity was always observed. Therefore, duck complement appears to be suitable for assay of hyperimmune chicken serum against MSB-1 cells by the CDAC test.", "contents": "Complement-dependent antibody cytotoxicity test of chicken antibody with duck complement used against cells of a Marek's disease lymphoma-derived cell line (MSB-1). Complement-dependent antibody cytotoxicity (CDAC) against cells of a lymphoblastoid cell line (MSB-1) derived from Marek's disease lymphoma was investigated in a chicken antibody system using complements from several animal species. Cytotoxicity was seldom observed when rabbit, guinea pig, or chicken complements were used in the presence of hyperimmune chicken serum against MSB-1. With duck complement, however, cytotoxicity was always observed. Therefore, duck complement appears to be suitable for assay of hyperimmune chicken serum against MSB-1 cells by the CDAC test."}
{"id": "PMID:226055", "title": "An infectious bursal disease virus outbreak in 14- and 15-week-old chickens.", "content": "Infectious bursal disease virus (IBDV) observed in a flock of 14- and 15-week-old chickens was typical of the acute symptomatic IBDV infections more common in younger birds. High flock morbidity was indicated by a marked decrease in feed consumption, although deaths were not excessive. At necropsy, affected birds had small hemorrhages in thigh muscles, creamy-yellow-colored bursae of Fabricius with prominent longitudinal striations, and swollen mottled kidneys. Histopathologic examination revealed bursal lesions typical of IBDV infection. One of six sera from necropsied birds was positive for antibody to IBDV in the agar-gel precipitin (AGP) test, and one week later all 35 samples tested were positive. Bursae were homogenized and found to contain IBDV as evidenced by precipitation, with antibody to IBDV, in the AGP test.", "contents": "An infectious bursal disease virus outbreak in 14- and 15-week-old chickens. Infectious bursal disease virus (IBDV) observed in a flock of 14- and 15-week-old chickens was typical of the acute symptomatic IBDV infections more common in younger birds. High flock morbidity was indicated by a marked decrease in feed consumption, although deaths were not excessive. At necropsy, affected birds had small hemorrhages in thigh muscles, creamy-yellow-colored bursae of Fabricius with prominent longitudinal striations, and swollen mottled kidneys. Histopathologic examination revealed bursal lesions typical of IBDV infection. One of six sera from necropsied birds was positive for antibody to IBDV in the agar-gel precipitin (AGP) test, and one week later all 35 samples tested were positive. Bursae were homogenized and found to contain IBDV as evidenced by precipitation, with antibody to IBDV, in the AGP test."}
{"id": "PMID:226056", "title": "Infectious bursal disease viral infections. I. Complement and virus-neutralizing antibody response following infection of susceptible chickens.", "content": "Complement (C) titers were decreased at 3 days postinfection, and virus-neutralizing (VN) antibody was detectable at 3 or 4 days postinfection in chickens with infectious bursal disease virus (IBDV). Clotting times were prolonged in all groups tested during the acute phase of the disease. Mortality appeared to be associated with the severity of decrease in C titer. The results suggest that the mortality and many of the clinical signs seen with infectious bursal disease are associated with: 1) a depletion in circulating levels of hemolytic C from the formation of immune complexes at sites of viral replication; and/or 2) a depletion in some clotting factor which results in hemorrhage.", "contents": "Infectious bursal disease viral infections. I. Complement and virus-neutralizing antibody response following infection of susceptible chickens. Complement (C) titers were decreased at 3 days postinfection, and virus-neutralizing (VN) antibody was detectable at 3 or 4 days postinfection in chickens with infectious bursal disease virus (IBDV). Clotting times were prolonged in all groups tested during the acute phase of the disease. Mortality appeared to be associated with the severity of decrease in C titer. The results suggest that the mortality and many of the clinical signs seen with infectious bursal disease are associated with: 1) a depletion in circulating levels of hemolytic C from the formation of immune complexes at sites of viral replication; and/or 2) a depletion in some clotting factor which results in hemorrhage."}
{"id": "PMID:226062", "title": "Immunogenetic study on the polymorphism of serum alpha 2-lipoprotein in mink. III. Ld1 allotype of low-density lipoprotein.", "content": "Mink Ldl antigen of serum low-density lipoprotein was demonstrated by alloantibodies. No genetic relation was found between Ldl and the Lpm system of very-high-density lipoprotein. The existence of an autosomal dominant gene, coding for the new alloantigenic marker, is postulated on the basis of mink breeding data.", "contents": "Immunogenetic study on the polymorphism of serum alpha 2-lipoprotein in mink. III. Ld1 allotype of low-density lipoprotein. Mink Ldl antigen of serum low-density lipoprotein was demonstrated by alloantibodies. No genetic relation was found between Ldl and the Lpm system of very-high-density lipoprotein. The existence of an autosomal dominant gene, coding for the new alloantigenic marker, is postulated on the basis of mink breeding data."}
{"id": "PMID:226063", "title": "Are polyphosphoinositides associated with glycophorin in human erythrocyte membranes?", "content": "Glycophorin prepared by a lithium di-iodosalicylate-extraction/phenol-partition method was rich in polyphosphoinositides (phosphatidyl-myo-inositol 4-phosphate and phosphatidyl-myo-inositol 4,5-bisphosphate), but glycophorin extracted by Triton X-100 showed no such enrichment. The enrichment observed in the former preparations appeared not to be caused by pre-existing association between glycophorin and polyphosphoinositides in the human erythrocyte membrane, but to be largely a consequence of the preparative procedures.", "contents": "Are polyphosphoinositides associated with glycophorin in human erythrocyte membranes? Glycophorin prepared by a lithium di-iodosalicylate-extraction/phenol-partition method was rich in polyphosphoinositides (phosphatidyl-myo-inositol 4-phosphate and phosphatidyl-myo-inositol 4,5-bisphosphate), but glycophorin extracted by Triton X-100 showed no such enrichment. The enrichment observed in the former preparations appeared not to be caused by pre-existing association between glycophorin and polyphosphoinositides in the human erythrocyte membrane, but to be largely a consequence of the preparative procedures."}
{"id": "PMID:226064", "title": "Regulation of ketogenesis during the suckling-weanling transition in the rat. Studies with isolated hepatocytes.", "content": "The rates of ketogenesis from endogenous substrates, butyrate or oleate, have been measured in isolated hepatocytes from suckling and weanling rats. Ketogenesis from endogenous substrate and from oleate decreased on weaning, whereas the rate from butyrate remained unchanged. It is concluded that the major site of regulation of ketogenesis during this period of development involves the disposal of long-chain fatty acyl-CoA between the esterification and beta-oxidation pathways. Modulators of lipogenesis [dihydroxyacetone and 5-(tetradecyloxy)-2-furoic acid] did not alter the rate of ketogenesis in hepatocytes from suckling rats, and it is suggested that this is due to the low rate of lipogenesis in these cells. Hepatocytes from fed weanling rats have a high rate of lipogenesis and evidence is presented for a reciprocal relationship between ketogenesis and lipogenesis, and ketogenesis, and esterification in these cells. Dibutyryl cyclic AMP stimulated ketogenesis from oleate in hepatocytes from fed weanling rats, even in the presence of an inhibitor of lipogenesis [5-(tetradecyloxy)-2-furoic acid], but not in cells from suckling rats. It is suggested that cyclic AMP may act via inhibition of esterification and that in hepatocytes from suckling rats ketogenesis is already maximally stimulated by the high basal concentrations of cyclic AMP [Beaudry, Chiasson & Exton (1977) Am. J. Physiol. 233, E175--E180].", "contents": "Regulation of ketogenesis during the suckling-weanling transition in the rat. Studies with isolated hepatocytes. The rates of ketogenesis from endogenous substrates, butyrate or oleate, have been measured in isolated hepatocytes from suckling and weanling rats. Ketogenesis from endogenous substrate and from oleate decreased on weaning, whereas the rate from butyrate remained unchanged. It is concluded that the major site of regulation of ketogenesis during this period of development involves the disposal of long-chain fatty acyl-CoA between the esterification and beta-oxidation pathways. Modulators of lipogenesis [dihydroxyacetone and 5-(tetradecyloxy)-2-furoic acid] did not alter the rate of ketogenesis in hepatocytes from suckling rats, and it is suggested that this is due to the low rate of lipogenesis in these cells. Hepatocytes from fed weanling rats have a high rate of lipogenesis and evidence is presented for a reciprocal relationship between ketogenesis and lipogenesis, and ketogenesis, and esterification in these cells. Dibutyryl cyclic AMP stimulated ketogenesis from oleate in hepatocytes from fed weanling rats, even in the presence of an inhibitor of lipogenesis [5-(tetradecyloxy)-2-furoic acid], but not in cells from suckling rats. It is suggested that cyclic AMP may act via inhibition of esterification and that in hepatocytes from suckling rats ketogenesis is already maximally stimulated by the high basal concentrations of cyclic AMP [Beaudry, Chiasson & Exton (1977) Am. J. Physiol. 233, E175--E180]."}
{"id": "PMID:226065", "title": "The involvement of glucocorticoids in regulating the activity of phosphatidate phosphohydrolase and the synthesis of triacylglycerols in the liver. Effects of feeding rats with glucose, sorbitol, fructose, glycerol and ethanol.", "content": "Feeding rats with sorbitol, fructose, glycerol and ethanol increases the concentration of serum corticosterone without significantly altering the concentration of insulin. This increase appears to be partly responsible for the increases in the hepatic activity of phosphatidate phosphohydrolase (compared with rats fed glucose or 0.9% NaCl) that has been reported [Sturton, Pritchard, Han & Brindley (1978) Biochem. J. 174, 667--670] and the enhanced capacity of the liver to synthesize triacylglycerols. The ethanol-induced increase in phosphohydrolase activity was largely, but not completely, prevented by adrenalectomy.", "contents": "The involvement of glucocorticoids in regulating the activity of phosphatidate phosphohydrolase and the synthesis of triacylglycerols in the liver. Effects of feeding rats with glucose, sorbitol, fructose, glycerol and ethanol. Feeding rats with sorbitol, fructose, glycerol and ethanol increases the concentration of serum corticosterone without significantly altering the concentration of insulin. This increase appears to be partly responsible for the increases in the hepatic activity of phosphatidate phosphohydrolase (compared with rats fed glucose or 0.9% NaCl) that has been reported [Sturton, Pritchard, Han & Brindley (1978) Biochem. J. 174, 667--670] and the enhanced capacity of the liver to synthesize triacylglycerols. The ethanol-induced increase in phosphohydrolase activity was largely, but not completely, prevented by adrenalectomy."}
{"id": "PMID:226066", "title": "Receptor-mediated gonadotropin action in the ovary. Regulatory role of cyclic nucleotide phosphodiesterase(s) in intracellular adenosine 3':5'-cyclic monophosphate turnover and gonadotropin-stimulated progesterone production by rat ovarian cells.", "content": "The regulatory role of cyclic nucleotide phosphodiesterase(s) and cyclic AMP metabolism in relation to progesterone production by gonadotropins has been studied in isolated rat ovarian cells. Low concentrations of choriogonadotropin (0.4-5ng/ml) increased steroid production without any detectable increase in cyclic AMP, when experiments were carried out in the absence of phosphodiesterase inhibitors. The concentration of choriogonadotropin (10ng/ml) that stimulated progesterone synthesis maximally resulted in a minimal increase in cyclic AMP accumulation and choriogonadotropin binding. Choriogonadotropin at a concentration of 10ng/ml and higher, however, significantly stimulated protein kinase activity and reached a maximum between 250 and 1000ng of hormone/ml. Higher concentrations (50-2500ng/ml) of choriogonadotropin caused an increase in endogenous cyclic AMP, and this increase preceded the increase in steroid synthesis. Analysis of dose-response relationships of gonadotropin-stimulated cyclic AMP accumulation, progesterone production and protein kinase activity revealed a correlation between these responses over a wide concentration range when experiments were performed in the presence of 3-isobutyl-1-methylxanthine. The phosphodiesterase inhibitors papaverine, theophylline and 3-isobutyl-1-methylxanthine each stimulated steroid production in a dose-dependent manner. Incubation of ovarian cells with dibutyryl cyclic AMP or 8-bromo cyclic AMP mimicked the steroidogenic action of gonadotropins and this effect was dependent on both incubation time and nucleotide concentration. Maximum stimulation was obtained with 2mm-dibutyryl cyclic AMP and 8-bromo cyclic AMP, and this increase was close to that produced by a maximally stimulating dose of choriogonadotropin. Other 8-substituted derivatives such as 8-hydroxy cyclic AMP and 8-isopropylthio cyclic AMP, which were less susceptible to phosphodiesterase action, also effectively stimulated steroidogenesis. The uptake and metabolism of cyclic [(3)H]AMP in ovarian cells was also studied in relation to steroidogenesis. When ovarian cells were incubated for 2h in the presence of increasing concentrations of cyclic [(3)H]AMP, the radioactivity associated with the cells increased almost linearly up to 250mum-cyclic [(3)H]AMP concentration in the incubation medium. The (3)H label in the cellular extract was recovered mainly in the forms ATP, ADP, AMP, adenosine and inosine, with cyclic AMP accounting for less than 1% of the total tissue radioactivity. Incubation of cyclic AMP in vitro with ovarian cells resulted in a rapid breakdown of the nucleotide in the medium. The degradation products in the medium have been identified as AMP, adenosine and inosine. The rapid degradation of cyclic AMP by phosphodiesterase(s) makes it difficult to correlate changes in cyclic AMP concentrations with steroidogenesis. These observations thus provide an explanation for the previously observed lack of cyclic AMP accumulation under conditions in which low doses of choriogonadotropin stimulated steroidogenesis without any detectable changes in cyclic AMP accumulation.", "contents": "Receptor-mediated gonadotropin action in the ovary. Regulatory role of cyclic nucleotide phosphodiesterase(s) in intracellular adenosine 3':5'-cyclic monophosphate turnover and gonadotropin-stimulated progesterone production by rat ovarian cells. The regulatory role of cyclic nucleotide phosphodiesterase(s) and cyclic AMP metabolism in relation to progesterone production by gonadotropins has been studied in isolated rat ovarian cells. Low concentrations of choriogonadotropin (0.4-5ng/ml) increased steroid production without any detectable increase in cyclic AMP, when experiments were carried out in the absence of phosphodiesterase inhibitors. The concentration of choriogonadotropin (10ng/ml) that stimulated progesterone synthesis maximally resulted in a minimal increase in cyclic AMP accumulation and choriogonadotropin binding. Choriogonadotropin at a concentration of 10ng/ml and higher, however, significantly stimulated protein kinase activity and reached a maximum between 250 and 1000ng of hormone/ml. Higher concentrations (50-2500ng/ml) of choriogonadotropin caused an increase in endogenous cyclic AMP, and this increase preceded the increase in steroid synthesis. Analysis of dose-response relationships of gonadotropin-stimulated cyclic AMP accumulation, progesterone production and protein kinase activity revealed a correlation between these responses over a wide concentration range when experiments were performed in the presence of 3-isobutyl-1-methylxanthine. The phosphodiesterase inhibitors papaverine, theophylline and 3-isobutyl-1-methylxanthine each stimulated steroid production in a dose-dependent manner. Incubation of ovarian cells with dibutyryl cyclic AMP or 8-bromo cyclic AMP mimicked the steroidogenic action of gonadotropins and this effect was dependent on both incubation time and nucleotide concentration. Maximum stimulation was obtained with 2mm-dibutyryl cyclic AMP and 8-bromo cyclic AMP, and this increase was close to that produced by a maximally stimulating dose of choriogonadotropin. Other 8-substituted derivatives such as 8-hydroxy cyclic AMP and 8-isopropylthio cyclic AMP, which were less susceptible to phosphodiesterase action, also effectively stimulated steroidogenesis. The uptake and metabolism of cyclic [(3)H]AMP in ovarian cells was also studied in relation to steroidogenesis. When ovarian cells were incubated for 2h in the presence of increasing concentrations of cyclic [(3)H]AMP, the radioactivity associated with the cells increased almost linearly up to 250mum-cyclic [(3)H]AMP concentration in the incubation medium. The (3)H label in the cellular extract was recovered mainly in the forms ATP, ADP, AMP, adenosine and inosine, with cyclic AMP accounting for less than 1% of the total tissue radioactivity. Incubation of cyclic AMP in vitro with ovarian cells resulted in a rapid breakdown of the nucleotide in the medium. The degradation products in the medium have been identified as AMP, adenosine and inosine. The rapid degradation of cyclic AMP by phosphodiesterase(s) makes it difficult to correlate changes in cyclic AMP concentrations with steroidogenesis. These observations thus provide an explanation for the previously observed lack of cyclic AMP accumulation under conditions in which low doses of choriogonadotropin stimulated steroidogenesis without any detectable changes in cyclic AMP accumulation."}
{"id": "PMID:226067", "title": "Protein kinase activities in rat pancreatic islets of Langerhans.", "content": "1. Protein kinase activities in homogenates of rat islets of Langerhans were studied. 2. On incubation of homogenates with [gamma-32P]ATP, incorporation of 32P into protein occurred: this phosphorylation was neither increased by cyclic AMP nor decreased by the cyclic AMP-dependent protein kinase inhibitor described by Ashby & Walsh [(1972) J. Biol. Chem. 247, 6637--6642]. 3. On incubation of homogenates with [gamma-32P]ATP and histone as exogenous substrate for phosphorylation, incorporation of 32P into protein was stimulated by cyclic AMP (approx. 2.5-fold) and was inhibited by the cyclic AMP-dependent protein kinase inhibitor. In contrast, when casein was used as exogenous substrate, incorporation of 32P into protein was not stimulated by cyclic AMP, nor was it inhibited by the cyclic AMP-dependent protein kinase inhibitor. 4. DEAE-cellulose ion-exchange chromatography resolved four peaks of protein kinase activity. One species was the free catalytic subunit of cyclic AMP-dependent protein kinase, two species corresponded to 'Type I' and 'Type II' cyclic AMP-dependent protein kinase holoenzymes [see Corbin, Keely & Park (1975) J. Biol. Chem. 250, 218--225], and the fourth species was a cyclic AMP-independent protein kinase. 5. Determination of physical and kinetic properties of the protein kinases showed that the properties of the cyclic AMP-dependent activities were similar to those described in other tissues and were clearly distinct from those of the cyclic AMP-independent protein kinase. 6. The cyclic AMP-independent protein kinase had an s20.w of 5.2S, phosphorylated a serine residue(s) in casein and was not inhibited by the cyclic AMP-dependent protein kinase inhibitor. 7. These studies demonstrate the existence in rat islets of Langerhans of multiple forms of cyclic AMP-dependent protein kinase and also the presence of a cyclic AMP-independent protein kinase distinct from the free catalytic subunit of cyclic AMP-dependent protein kinase. The presence of the cyclic AMP-independent protein kinase may account for the observed characteristics of 32P incorporation into endogenous protein in homogenates of rat islets.", "contents": "Protein kinase activities in rat pancreatic islets of Langerhans. 1. Protein kinase activities in homogenates of rat islets of Langerhans were studied. 2. On incubation of homogenates with [gamma-32P]ATP, incorporation of 32P into protein occurred: this phosphorylation was neither increased by cyclic AMP nor decreased by the cyclic AMP-dependent protein kinase inhibitor described by Ashby & Walsh [(1972) J. Biol. Chem. 247, 6637--6642]. 3. On incubation of homogenates with [gamma-32P]ATP and histone as exogenous substrate for phosphorylation, incorporation of 32P into protein was stimulated by cyclic AMP (approx. 2.5-fold) and was inhibited by the cyclic AMP-dependent protein kinase inhibitor. In contrast, when casein was used as exogenous substrate, incorporation of 32P into protein was not stimulated by cyclic AMP, nor was it inhibited by the cyclic AMP-dependent protein kinase inhibitor. 4. DEAE-cellulose ion-exchange chromatography resolved four peaks of protein kinase activity. One species was the free catalytic subunit of cyclic AMP-dependent protein kinase, two species corresponded to 'Type I' and 'Type II' cyclic AMP-dependent protein kinase holoenzymes [see Corbin, Keely & Park (1975) J. Biol. Chem. 250, 218--225], and the fourth species was a cyclic AMP-independent protein kinase. 5. Determination of physical and kinetic properties of the protein kinases showed that the properties of the cyclic AMP-dependent activities were similar to those described in other tissues and were clearly distinct from those of the cyclic AMP-independent protein kinase. 6. The cyclic AMP-independent protein kinase had an s20.w of 5.2S, phosphorylated a serine residue(s) in casein and was not inhibited by the cyclic AMP-dependent protein kinase inhibitor. 7. These studies demonstrate the existence in rat islets of Langerhans of multiple forms of cyclic AMP-dependent protein kinase and also the presence of a cyclic AMP-independent protein kinase distinct from the free catalytic subunit of cyclic AMP-dependent protein kinase. The presence of the cyclic AMP-independent protein kinase may account for the observed characteristics of 32P incorporation into endogenous protein in homogenates of rat islets."}
{"id": "PMID:226068", "title": "Comparison of permeant ion uptake and carotenoid band shift as methods for determining the membrane potential in chromatophores from Rhodopseudomonas sphaeroides Ga.", "content": "1. A comparison was made of two methods for estimating the membrane potential in chromatophores from Rhodopseudomonas sphaeroides Ga. Illuminated chromatophores generated a potential that is apparently much larger when estimated on the basis of the red-band shift of carotenoids rather than from the extent of uptake of the permeant SCN- ion. 2. In contrast, when the chromatophores were oxidizing NADH or succinate the uptake of SCN- indicated a larger membrane potential than was estimated from the carotenoid band shift. 3. The extent of SCN- uptake and the carotenoid-band shift respond differently to changes in the ionic composition of the reaction medium. 4. The effects of antimycin on the carotenoid band shift and SCN- uptake are reported. 5. It is concluded that the carotenoid band shift and the uptake of SCN- are responding to different aspects of the energized state.", "contents": "Comparison of permeant ion uptake and carotenoid band shift as methods for determining the membrane potential in chromatophores from Rhodopseudomonas sphaeroides Ga. 1. A comparison was made of two methods for estimating the membrane potential in chromatophores from Rhodopseudomonas sphaeroides Ga. Illuminated chromatophores generated a potential that is apparently much larger when estimated on the basis of the red-band shift of carotenoids rather than from the extent of uptake of the permeant SCN- ion. 2. In contrast, when the chromatophores were oxidizing NADH or succinate the uptake of SCN- indicated a larger membrane potential than was estimated from the carotenoid band shift. 3. The extent of SCN- uptake and the carotenoid-band shift respond differently to changes in the ionic composition of the reaction medium. 4. The effects of antimycin on the carotenoid band shift and SCN- uptake are reported. 5. It is concluded that the carotenoid band shift and the uptake of SCN- are responding to different aspects of the energized state."}
{"id": "PMID:226069", "title": "Total, latent and active collagenase during the course of post-partum involution of the rat uterus. Effect of oestradiol.", "content": "1. Total, active and latent collagenase activities were determined by direct assay of tissue homogenates. 2. The rate of collagen breakdown during post-partum involution of the rat uterus is correlated with the total activity of collagenase. Both are low at parturition, reach a maximum within 24h and fall slowly to low values of 5 days post partum. This temporal correlation strongly supports the hypothesis that collagenase participates in collagen breakdown in vivo. 3. Further support for this hypothesis is provided by the finding that oestradiol-17 beta (100 micrograms/day, intraperitoneally injected), which inhibits the breakdown of collagen by 36% during the first 4 days of involution, produces a closely corresponding decrease in total collagenase activity. 3. The effect of oestradiol in lowering collagenase activity is not due to alterations in collagen substrate, collagenase kinetic behaviour or latent-to-active enzyme conversion. 4. Of the total assayable collagenase, about 35% is fully active and 65% is in a latent form. 5. About 70% of this latent form can be activated by a serine proteinase found, together with collagenase, in the insoluble fraction of uterine homogenates.", "contents": "Total, latent and active collagenase during the course of post-partum involution of the rat uterus. Effect of oestradiol. 1. Total, active and latent collagenase activities were determined by direct assay of tissue homogenates. 2. The rate of collagen breakdown during post-partum involution of the rat uterus is correlated with the total activity of collagenase. Both are low at parturition, reach a maximum within 24h and fall slowly to low values of 5 days post partum. This temporal correlation strongly supports the hypothesis that collagenase participates in collagen breakdown in vivo. 3. Further support for this hypothesis is provided by the finding that oestradiol-17 beta (100 micrograms/day, intraperitoneally injected), which inhibits the breakdown of collagen by 36% during the first 4 days of involution, produces a closely corresponding decrease in total collagenase activity. 3. The effect of oestradiol in lowering collagenase activity is not due to alterations in collagen substrate, collagenase kinetic behaviour or latent-to-active enzyme conversion. 4. Of the total assayable collagenase, about 35% is fully active and 65% is in a latent form. 5. About 70% of this latent form can be activated by a serine proteinase found, together with collagenase, in the insoluble fraction of uterine homogenates."}
{"id": "PMID:226071", "title": "Effects of diffusible products of peroxidation of rat liver microsomal lipids.", "content": "The effects on cellular structures of products of peroxidation of rat liver microsomal lipids were investigated. A system containing actively peroxidizing liver microsomal fraction was separated from a revealing or target system by a dialysis membrane. The target system, contained in the dialysis tube, consisted of either intact cells (erythrocytes) or subcellular fractions (liver microsomal fraction). When liver microsomal fractions were incubated with NADPH (or an NADPH-generating system), lipid peroxidation, as measured by the amount of malonaldehyde formed, occurred very rapidly. The malon-aldehyde concentration tended to equilibrate across the dialysis membrane. When the target system consisted of erythrocytes, haemolysis occurred abruptly after a lag phase. The lysis was greatly accelerated when erythrocytes from vitamin E-deficient rats were used, but no haemolysis was observed when erythrocytes from vitamin E-treated rats were used. When, in the same system, freshly prepared liver microsomal fractions were exposed to diffusible factors produced by lipid peroxidation, the glucose 6-phosphatase activity markedly decreased. A similar decrease in glucose 6-phosphatase activity, as well as a smaller but significant decrease in cytochrome P-450, was observed when the target microsomal fractions were exposed to diffusible factors derived from the peroxidation of liver microsomal lipids in a separate preincubation step. These and additional experiments indicated that the toxicological activity is relatively stable. Experiments in which the hepatic microsomal fractions destined for lipid peroxidation contained radioactively labelled arachidonic acid, previously incorporated into the membranes, showed that part of the radioactivity released from the microsomal fraction into the incubation medium entered the dialysis tube and was recovered bound to the constituents of the microsomal fractions of the target system. These results indicate that during the course of the peroxidation of liver microsomal lipids toxic products are formed that are able to induce pathological effects at distant loci.", "contents": "Effects of diffusible products of peroxidation of rat liver microsomal lipids. The effects on cellular structures of products of peroxidation of rat liver microsomal lipids were investigated. A system containing actively peroxidizing liver microsomal fraction was separated from a revealing or target system by a dialysis membrane. The target system, contained in the dialysis tube, consisted of either intact cells (erythrocytes) or subcellular fractions (liver microsomal fraction). When liver microsomal fractions were incubated with NADPH (or an NADPH-generating system), lipid peroxidation, as measured by the amount of malonaldehyde formed, occurred very rapidly. The malon-aldehyde concentration tended to equilibrate across the dialysis membrane. When the target system consisted of erythrocytes, haemolysis occurred abruptly after a lag phase. The lysis was greatly accelerated when erythrocytes from vitamin E-deficient rats were used, but no haemolysis was observed when erythrocytes from vitamin E-treated rats were used. When, in the same system, freshly prepared liver microsomal fractions were exposed to diffusible factors produced by lipid peroxidation, the glucose 6-phosphatase activity markedly decreased. A similar decrease in glucose 6-phosphatase activity, as well as a smaller but significant decrease in cytochrome P-450, was observed when the target microsomal fractions were exposed to diffusible factors derived from the peroxidation of liver microsomal lipids in a separate preincubation step. These and additional experiments indicated that the toxicological activity is relatively stable. Experiments in which the hepatic microsomal fractions destined for lipid peroxidation contained radioactively labelled arachidonic acid, previously incorporated into the membranes, showed that part of the radioactivity released from the microsomal fraction into the incubation medium entered the dialysis tube and was recovered bound to the constituents of the microsomal fractions of the target system. These results indicate that during the course of the peroxidation of liver microsomal lipids toxic products are formed that are able to induce pathological effects at distant loci."}
{"id": "PMID:226070", "title": "Effects of ethynyloestradiol on the metabolism of [1-14C]oleate by perfused livers and hepatocytes from female rats.", "content": "Normal female rats were given 15mug of ethynyloestradiol/kg body wt. for 14 days and were killed on day 15 after starvation for 12-14h. The livers were isolated and were perfused with a medium containing washed bovine erythrocytes, bovine serum albumin, glucose and [1-(14)C]oleic acid; 414mumol of oleate were infused/h during a 3h experimental period. The output of bile and the flow of perfusate/g of liver were decreased in livers from animals pretreated with ethynyloestradiol, whereas the liver weight was increased slightly. The rates of uptake and of utilization of [1-(14)C]oleate were measured when the concentration of unesterified fatty acid in the perfusate plasma was constant. The uptake of unesterified fatty acid was unaffected by pretreatment of the animal with oestrogen; however, the rate of incorporation of [1-(14)C]oleate into hepatic and perfusate triacylglycerol was stimulated, whereas the rate of conversion into ketone bodies was impaired by treatment of the rat with ethynyloestradiol. Pretreatment of the rat with ethynyloestradiol increased the output of very-low-density lipoprotein triacylglycerol, cholesterol, phospholipid and protein. The production of (14)CO(2) and the incorporation of radioactivity into phospholipid, cholesteryl ester and diacylglycerol was unaffected by treatment with the steroid. The net output of glucose by livers from oestrogen-treated rats was impaired despite the apparent increased quantities of glycogen in the liver. The overall effect of pretreatment with oestrogen on hepatic metabolism of fatty acids is the channeling of [1-(14)C]oleate into synthesis and increased output of triacylglycerol as a moiety of the very-low-density lipoprotein, whereas ketogenesis is decreased. The effect of ethynyloestradiol on the liver is apparently independent of the nutritional state of the animal from which the liver was obtained. It is pertinent that hepatocytes prepared from livers of fed rats that had been treated with ethynyloestradiol produced fewer ketone bodies and secreted more triacylglycerol than did hepatocytes prepared from control animals. In these respects, the effects of the steroid were similar in livers from fed or starved (12-14h) rats. Oestrogens may possibly inhibit hepatic oxidation of fatty acid, making more fatty acid available for the synthesis of triacylglycerol, or may stimulate the biosynthesis of triacylglycerol, or may be active on both metabolic pathways.", "contents": "Effects of ethynyloestradiol on the metabolism of [1-14C]oleate by perfused livers and hepatocytes from female rats. Normal female rats were given 15mug of ethynyloestradiol/kg body wt. for 14 days and were killed on day 15 after starvation for 12-14h. The livers were isolated and were perfused with a medium containing washed bovine erythrocytes, bovine serum albumin, glucose and [1-(14)C]oleic acid; 414mumol of oleate were infused/h during a 3h experimental period. The output of bile and the flow of perfusate/g of liver were decreased in livers from animals pretreated with ethynyloestradiol, whereas the liver weight was increased slightly. The rates of uptake and of utilization of [1-(14)C]oleate were measured when the concentration of unesterified fatty acid in the perfusate plasma was constant. The uptake of unesterified fatty acid was unaffected by pretreatment of the animal with oestrogen; however, the rate of incorporation of [1-(14)C]oleate into hepatic and perfusate triacylglycerol was stimulated, whereas the rate of conversion into ketone bodies was impaired by treatment of the rat with ethynyloestradiol. Pretreatment of the rat with ethynyloestradiol increased the output of very-low-density lipoprotein triacylglycerol, cholesterol, phospholipid and protein. The production of (14)CO(2) and the incorporation of radioactivity into phospholipid, cholesteryl ester and diacylglycerol was unaffected by treatment with the steroid. The net output of glucose by livers from oestrogen-treated rats was impaired despite the apparent increased quantities of glycogen in the liver. The overall effect of pretreatment with oestrogen on hepatic metabolism of fatty acids is the channeling of [1-(14)C]oleate into synthesis and increased output of triacylglycerol as a moiety of the very-low-density lipoprotein, whereas ketogenesis is decreased. The effect of ethynyloestradiol on the liver is apparently independent of the nutritional state of the animal from which the liver was obtained. It is pertinent that hepatocytes prepared from livers of fed rats that had been treated with ethynyloestradiol produced fewer ketone bodies and secreted more triacylglycerol than did hepatocytes prepared from control animals. In these respects, the effects of the steroid were similar in livers from fed or starved (12-14h) rats. Oestrogens may possibly inhibit hepatic oxidation of fatty acid, making more fatty acid available for the synthesis of triacylglycerol, or may stimulate the biosynthesis of triacylglycerol, or may be active on both metabolic pathways."}
{"id": "PMID:226072", "title": "Steroidogenesis in isolated adrenocortical cells. Correlation with receptor-bound adenosine e 3':5'-cyclic monophosphate.", "content": "Because several groups have recently questioned a mediating role for cyclic AMP in adrenocortical steroidogenesis, we analysed the problem in more detail by measuring three different cyclic AMP pools in cells isolated from decapsulated rat adrenals. Extra-cellular, total intracellular and bound intracellular cyclic AMP were determined by radioimmunoassay in comparison with corticosterone production induced by low corticotropin concentrations. The increase in extracellular and total intracellular cyclic AMP with low corticotropin concentrations was dependent on the presence of a phosphodiesterase inhibitor and short incubation times. Bound intracellular cyclic AMP was less dependent on these two parameters. In unstimulated cells cyclic AMP bound to its receptor represents only a small fraction of the total intracellular cyclic AMP. After stimulation by a concentration of corticotropin around the threshold for corticosterone production, an increase in bound cyclic AMP was observed which correlated very well with steroidogenesis both temporally and with respect to corticotropin concentration. This finding was complemented by measuring a concomitant decrease in free receptor sites. Full occupancy of the receptors was not necessary for maximal steroidogenesis. Binding kinetics of cyclic [(3)H]AMP in concentrations equivalent to the intracellular cyclic AMP concentration suggest the presence of at least three different intracellular cyclic AMP pools. These observations are in agreement with a possible role for cyclic AMP as a mediator of acute steroidogenesis induced by low corticotropin concentrations.", "contents": "Steroidogenesis in isolated adrenocortical cells. Correlation with receptor-bound adenosine e 3':5'-cyclic monophosphate. Because several groups have recently questioned a mediating role for cyclic AMP in adrenocortical steroidogenesis, we analysed the problem in more detail by measuring three different cyclic AMP pools in cells isolated from decapsulated rat adrenals. Extra-cellular, total intracellular and bound intracellular cyclic AMP were determined by radioimmunoassay in comparison with corticosterone production induced by low corticotropin concentrations. The increase in extracellular and total intracellular cyclic AMP with low corticotropin concentrations was dependent on the presence of a phosphodiesterase inhibitor and short incubation times. Bound intracellular cyclic AMP was less dependent on these two parameters. In unstimulated cells cyclic AMP bound to its receptor represents only a small fraction of the total intracellular cyclic AMP. After stimulation by a concentration of corticotropin around the threshold for corticosterone production, an increase in bound cyclic AMP was observed which correlated very well with steroidogenesis both temporally and with respect to corticotropin concentration. This finding was complemented by measuring a concomitant decrease in free receptor sites. Full occupancy of the receptors was not necessary for maximal steroidogenesis. Binding kinetics of cyclic [(3)H]AMP in concentrations equivalent to the intracellular cyclic AMP concentration suggest the presence of at least three different intracellular cyclic AMP pools. These observations are in agreement with a possible role for cyclic AMP as a mediator of acute steroidogenesis induced by low corticotropin concentrations."}
{"id": "PMID:226073", "title": "Inhibition of ribonucleic acid efflux from isolated SV40-3T3 cell nuclei by 3'-deoxyadenosine (cordycepin).", "content": "The effect of 3'-deoxyadenosine (cordycepin) on mRNA efflux from isolated SV40-3T3 cell nuclei has been studied and compared with its effect on the nucleoside triphosphatase activity in the isolated nuclear envelope. Inhibition of mRNA efflux occurs rapidly, but is dependent on the presence of ATP. Half-maximal inhibition occurs with 40 microM-cordycepin. The effect is not simulated by 2'-deoxyadenosine or by actinomycin D, and adenosine provides a substantial degree of protection against it. Cordycepin does not directly inhibit the nucleoside triphosphatase. The stimulation of this enzyme by poly(A) is not affected unless the poly(A) and cordycepin are incubated together with nuclear lysate in the presence of ATP; in this case the stimulation is significantly reduced. Possible interpretations of these results and their relevance for understanding the system in vivo for nucleo-cytoplasmic messenger transport are discussed.", "contents": "Inhibition of ribonucleic acid efflux from isolated SV40-3T3 cell nuclei by 3'-deoxyadenosine (cordycepin). The effect of 3'-deoxyadenosine (cordycepin) on mRNA efflux from isolated SV40-3T3 cell nuclei has been studied and compared with its effect on the nucleoside triphosphatase activity in the isolated nuclear envelope. Inhibition of mRNA efflux occurs rapidly, but is dependent on the presence of ATP. Half-maximal inhibition occurs with 40 microM-cordycepin. The effect is not simulated by 2'-deoxyadenosine or by actinomycin D, and adenosine provides a substantial degree of protection against it. Cordycepin does not directly inhibit the nucleoside triphosphatase. The stimulation of this enzyme by poly(A) is not affected unless the poly(A) and cordycepin are incubated together with nuclear lysate in the presence of ATP; in this case the stimulation is significantly reduced. Possible interpretations of these results and their relevance for understanding the system in vivo for nucleo-cytoplasmic messenger transport are discussed."}
{"id": "PMID:226074", "title": "Control of hepatic triacylglycerol synthesis. Diurnal variations in hepatic phosphatidate phosphohydrolase activity and in the concentrations of circulating insulin and corticosterone in rats.", "content": "Male rats were kept for 14 days with alternating 12h periods of light and darkness. The hepatic activity of soluble phosphatidate phosphohydrolase and the concentration of serum insulin were maximum at about 2h after dark. The peak concentration of serum corticosterone occurred 2h before the dark period. It is proposed that corticosterone is partly responsible for the increased phosphohydrolase activity, and that this enables the liver to increase its capacity to synthesize triacylglycerols during the period of maximum feeding.", "contents": "Control of hepatic triacylglycerol synthesis. Diurnal variations in hepatic phosphatidate phosphohydrolase activity and in the concentrations of circulating insulin and corticosterone in rats. Male rats were kept for 14 days with alternating 12h periods of light and darkness. The hepatic activity of soluble phosphatidate phosphohydrolase and the concentration of serum insulin were maximum at about 2h after dark. The peak concentration of serum corticosterone occurred 2h before the dark period. It is proposed that corticosterone is partly responsible for the increased phosphohydrolase activity, and that this enables the liver to increase its capacity to synthesize triacylglycerols during the period of maximum feeding."}
{"id": "PMID:226075", "title": "Poly(adenosine diphosphate ribose) synthetase activity in nuclei of dividing and of non-dividing but differentiating intestinal epithelial cells.", "content": "Poly(ADP-ribose) synthetase activity is found in nuclei of regenerating epithelial cells in the lower half of the crypts of guinea-pig small intestine. Nuclei from non-dividing but differentiating and maturing cells in the upper crypts and on the villi contain no more than about 10% of the synthetase activity of lower-crypt cell nuclei. The product in the active nuclei is shown to be 80% poly(ADP-ribosylated) protein and 20% mono(ADP-ribosylated) protein; 60% of thetotal labelled product was attached to acid-soluble proteins (including histones), and 40% to acid-insoluble (non-histone) proteins. The average number of ADP-ribosyl units in the oligomeric chains of the poly(ADP-ribosylated) proteins was 15 but the range of sizes of (ADP-ribose) oligomers attached to nuclear proteins was smaller in villus than in crypt cell nuclei.", "contents": "Poly(adenosine diphosphate ribose) synthetase activity in nuclei of dividing and of non-dividing but differentiating intestinal epithelial cells. Poly(ADP-ribose) synthetase activity is found in nuclei of regenerating epithelial cells in the lower half of the crypts of guinea-pig small intestine. Nuclei from non-dividing but differentiating and maturing cells in the upper crypts and on the villi contain no more than about 10% of the synthetase activity of lower-crypt cell nuclei. The product in the active nuclei is shown to be 80% poly(ADP-ribosylated) protein and 20% mono(ADP-ribosylated) protein; 60% of thetotal labelled product was attached to acid-soluble proteins (including histones), and 40% to acid-insoluble (non-histone) proteins. The average number of ADP-ribosyl units in the oligomeric chains of the poly(ADP-ribosylated) proteins was 15 but the range of sizes of (ADP-ribose) oligomers attached to nuclear proteins was smaller in villus than in crypt cell nuclei."}
{"id": "PMID:226077", "title": "Evidence for the importance of arginine residues in pig kidney alkaline phosphatase.", "content": "The arginine-specific reagents 2,3-butanedione and phenylglyoxal inactivate pig kidney alkaline phosphatase. As inactivation proceeds there is a progressive fall in Vmax. of the enzyme, but no demonstrable change in the Km value for substrate. Pi, a competitive inhibitor, and AMP, a substrate of the enzyme, protect alkaline phosphatase against the arginine-specific reagents. These effects are explicable by the assumption that the enzyme contains an essential arginine residue at the active site. Protection is also afforded by the uncompetitive inhibitor NADH through a partially competive action against the reagents. Enzyme that has been exposed to the reagents has a decreased sensitivity to NADH inhibition. It is suggested that an arginine residue is important for NADH binding also, although this residue is distinct from that at the catalytic site. The protection given by NADH against loss of activity is indicative of the close proximity of the active and NADH sites.", "contents": "Evidence for the importance of arginine residues in pig kidney alkaline phosphatase. The arginine-specific reagents 2,3-butanedione and phenylglyoxal inactivate pig kidney alkaline phosphatase. As inactivation proceeds there is a progressive fall in Vmax. of the enzyme, but no demonstrable change in the Km value for substrate. Pi, a competitive inhibitor, and AMP, a substrate of the enzyme, protect alkaline phosphatase against the arginine-specific reagents. These effects are explicable by the assumption that the enzyme contains an essential arginine residue at the active site. Protection is also afforded by the uncompetitive inhibitor NADH through a partially competive action against the reagents. Enzyme that has been exposed to the reagents has a decreased sensitivity to NADH inhibition. It is suggested that an arginine residue is important for NADH binding also, although this residue is distinct from that at the catalytic site. The protection given by NADH against loss of activity is indicative of the close proximity of the active and NADH sites."}
{"id": "PMID:226078", "title": "Inhibition of rat liver mevalonate pyrophosphate decarboxylase and mevalonate phosphate kinase by phenyl and phenolic compounds.", "content": "1. Mevalonate pyrophosphate decarboxylase of rat liver is inhibited by various phenyl and phenolic acids. 2. Some of the phenyl and phenolic acids also inhibited mevalonate phosphate kinase. 3. Compounds with the phenyl-vinyl structure were more effective. 4. Kinetic studies showed that some of the phenolic acids compete with the substrates, mevalonate 5-phosphate and mevalonate 5-pyrophosphate, whereas others inhibit umcompetitively. 5. Dihydroxyphenyl and trihydroxyphenyl compounds and p-chlorophenoxyisobutyrate, a hypocholesterolaemic drug, had no effect on these enzymes. 6. Of the three mevalonate-metabolizing enzymes, mevalonate pyrophosphate decarboxylase has the lowest specific activity and is probably the rate-determining step in this part of the pathway.", "contents": "Inhibition of rat liver mevalonate pyrophosphate decarboxylase and mevalonate phosphate kinase by phenyl and phenolic compounds. 1. Mevalonate pyrophosphate decarboxylase of rat liver is inhibited by various phenyl and phenolic acids. 2. Some of the phenyl and phenolic acids also inhibited mevalonate phosphate kinase. 3. Compounds with the phenyl-vinyl structure were more effective. 4. Kinetic studies showed that some of the phenolic acids compete with the substrates, mevalonate 5-phosphate and mevalonate 5-pyrophosphate, whereas others inhibit umcompetitively. 5. Dihydroxyphenyl and trihydroxyphenyl compounds and p-chlorophenoxyisobutyrate, a hypocholesterolaemic drug, had no effect on these enzymes. 6. Of the three mevalonate-metabolizing enzymes, mevalonate pyrophosphate decarboxylase has the lowest specific activity and is probably the rate-determining step in this part of the pathway."}
{"id": "PMID:226079", "title": "Steady-state investigations of the mechanism of histidinol dehydrogenase.", "content": "Initial velocities of the histidinol dehydrogenase reaction (EC 1.1.1.23) were measured as a function of the concentrations of the substrates histidinol and NAD+ and in the presence and absence of the product NADH. The data are consistent with a Bi Uni Uni Bi Ping Pong mechanism. The kinetic constants of this mechanism were determined; Km for histidinol was found to be 14 microM and for NAD+ 0.7 mV; Ki for NAD+ was 0.4 mM.", "contents": "Steady-state investigations of the mechanism of histidinol dehydrogenase. Initial velocities of the histidinol dehydrogenase reaction (EC 1.1.1.23) were measured as a function of the concentrations of the substrates histidinol and NAD+ and in the presence and absence of the product NADH. The data are consistent with a Bi Uni Uni Bi Ping Pong mechanism. The kinetic constants of this mechanism were determined; Km for histidinol was found to be 14 microM and for NAD+ 0.7 mV; Ki for NAD+ was 0.4 mM."}
{"id": "PMID:226080", "title": "Isolation and properties of cytochrome c peroxidase from Pseudomonas denitrificans.", "content": "The isolation of cytochrome c peroxidase, cytochrome c4, cytochrome c-551 and azurin from Pseudomonas dentrificans is described. The peroxidase has a molecular weight of 63,000 and an isoelectric point of 5.6. Its absorption spectrum suggests that it contains two haem c groups/molecule. Preliminary steady-state kinetic data are reported with cytochromes c-551 and c4 and azurin as the second substrate.", "contents": "Isolation and properties of cytochrome c peroxidase from Pseudomonas denitrificans. The isolation of cytochrome c peroxidase, cytochrome c4, cytochrome c-551 and azurin from Pseudomonas dentrificans is described. The peroxidase has a molecular weight of 63,000 and an isoelectric point of 5.6. Its absorption spectrum suggests that it contains two haem c groups/molecule. Preliminary steady-state kinetic data are reported with cytochromes c-551 and c4 and azurin as the second substrate."}
{"id": "PMID:226081", "title": "Intermediate dehydrogenase-oxidase form of xanthine oxidoreductase in rat liver.", "content": "A spectrophotometric method for the determination of three forms of xanthine oxidoreductase, namely dehydrogenase (D), dehydrogenase-oxidase (D/O) and oxidase (O), is described. Enzymic fractions obtained from rat liver were found to contain either all three forms, or (under special conditions of preparation) only two forms, D and D/O. The conversion of form D leads to form D/O leads to form O in the presence of Cu2+ ions was shown. Form D/O acted with NAD+ as well as with O2 as electron acceptors, it exhibited greater affinity to NAD+ than to O2, and NAD+ abolished the oxidase activity of this form. Moreover, oxidase activity of form D/O was inhibited by NADH. These facts indicate that NAD+ and O2 compete for the same active site on the enzyme molecule.", "contents": "Intermediate dehydrogenase-oxidase form of xanthine oxidoreductase in rat liver. A spectrophotometric method for the determination of three forms of xanthine oxidoreductase, namely dehydrogenase (D), dehydrogenase-oxidase (D/O) and oxidase (O), is described. Enzymic fractions obtained from rat liver were found to contain either all three forms, or (under special conditions of preparation) only two forms, D and D/O. The conversion of form D leads to form D/O leads to form O in the presence of Cu2+ ions was shown. Form D/O acted with NAD+ as well as with O2 as electron acceptors, it exhibited greater affinity to NAD+ than to O2, and NAD+ abolished the oxidase activity of this form. Moreover, oxidase activity of form D/O was inhibited by NADH. These facts indicate that NAD+ and O2 compete for the same active site on the enzyme molecule."}
{"id": "PMID:226082", "title": "Biosynthesis of proline in Pseudomonas aeruginosa. Partial purification and characterization of gamma-glutamyl kinase.", "content": "A gamma-glutamyl kinase (ATP-L-glutamate 5-phosphotransferase) was purified about 85-fold from crude extracts of Pseudomonas aeruginosa strain PAO 1 by (NH4)2SO4 precipitation, molecular-sieving by Sephadex G-150 and DEAE-cellulose chromatography. The molecular weight of this enzyme was 84,000. The preparation catalysed formation of gamma-glutamyl hydroxamate from L-glutamate, ATP and Mg2+ or Mn2+ with concomitant hydrolysis of ATP to ADP + Pi. L-Proline inhibited the gamma-glutamyl kinase activity by 50% at 5 mM and almost completely at 30 mM. The inhibition of L-proline was non-competitive, wherease L-methionine-DL-sulphoximine inhibited the enzyme competitively. Proline was found to inhibit the gamma-glutamyl kinase activity of the wild-type strain and of representatives of two of the three transductional classes of proline-auxotrophic mutants. Strain PAO 879, a mutant representing the third transductional class of proline auxotrophs, lacked proline-inhibitible gamma-glutamyl kinase. Thiol-blocking reagents inhibited the gamma-glutamyl kinase and this effect was prevented by dithiothreitol.", "contents": "Biosynthesis of proline in Pseudomonas aeruginosa. Partial purification and characterization of gamma-glutamyl kinase. A gamma-glutamyl kinase (ATP-L-glutamate 5-phosphotransferase) was purified about 85-fold from crude extracts of Pseudomonas aeruginosa strain PAO 1 by (NH4)2SO4 precipitation, molecular-sieving by Sephadex G-150 and DEAE-cellulose chromatography. The molecular weight of this enzyme was 84,000. The preparation catalysed formation of gamma-glutamyl hydroxamate from L-glutamate, ATP and Mg2+ or Mn2+ with concomitant hydrolysis of ATP to ADP + Pi. L-Proline inhibited the gamma-glutamyl kinase activity by 50% at 5 mM and almost completely at 30 mM. The inhibition of L-proline was non-competitive, wherease L-methionine-DL-sulphoximine inhibited the enzyme competitively. Proline was found to inhibit the gamma-glutamyl kinase activity of the wild-type strain and of representatives of two of the three transductional classes of proline-auxotrophic mutants. Strain PAO 879, a mutant representing the third transductional class of proline auxotrophs, lacked proline-inhibitible gamma-glutamyl kinase. Thiol-blocking reagents inhibited the gamma-glutamyl kinase and this effect was prevented by dithiothreitol."}
{"id": "PMID:226097", "title": "Collagenase production by synovial fibroblasts treated with phorbol myristate acetate.", "content": "A series of intracellular events occurring after treatment of rabbit synovial fibroblasts with 0.01 micrograms/ml phorbol myristate acetate (PMA) were measured. Ten minutes after addition of PMA, there was a temporary increase in intracellular cyclic AMP levels, followed by a transient decrease in incorporation of 3H-thymidine into DNA. Approximately 500 ng/mg cell protein of PGE2 were found in culture medium from the 12- to 24-hour incubation period, but significant collagenase was not detectable until 24 to 36 hours. Treatment with aspirin or indomethacin abolished PGE2 production but did not affect collagenase levels. Production of enzyme was associated with a cessation of cell proliferation, measured by protein content/culture and cell number. No enzyme was detectable in untreated cultures. Synovial fibroblasts treated with phorbol myristate acetate may provide a good model for studies on the mechanism of induction of collagenase production.", "contents": "Collagenase production by synovial fibroblasts treated with phorbol myristate acetate. A series of intracellular events occurring after treatment of rabbit synovial fibroblasts with 0.01 micrograms/ml phorbol myristate acetate (PMA) were measured. Ten minutes after addition of PMA, there was a temporary increase in intracellular cyclic AMP levels, followed by a transient decrease in incorporation of 3H-thymidine into DNA. Approximately 500 ng/mg cell protein of PGE2 were found in culture medium from the 12- to 24-hour incubation period, but significant collagenase was not detectable until 24 to 36 hours. Treatment with aspirin or indomethacin abolished PGE2 production but did not affect collagenase levels. Production of enzyme was associated with a cessation of cell proliferation, measured by protein content/culture and cell number. No enzyme was detectable in untreated cultures. Synovial fibroblasts treated with phorbol myristate acetate may provide a good model for studies on the mechanism of induction of collagenase production."}
{"id": "PMID:226098", "title": "CLearance of calcium pyrophosphate dihydrate crystals in vivo. II. Studies using triclinic crystals doubly labeled with 45Ca and 85Sr.", "content": "The clearance rate of isotopically labeled synthetic triclinic calcium pyrophosphate dihydrate (CPPD) crystals injection into rabbit joints was estimated by serial counting. Kinetic analysis using a four compartment model showed that half of the injected dose was cleared from 4 rabbit knee joints in 19.1 +/- 0.42 (SEM) days. Profound hypomagnesemia, produced in 2 rabbits with a low magnesium diet, did not affect the rate of crystal clearance detectably. Lavage of joints with solutions known to promote CPPD crystal solubility failed to remove detectable radioactivity. The previous finding of CPPD crystals in synovial phagocytes by electron microscopy, together with the finding of nuclide activity in the synovium and the failure to remove such activity by joint lavage, suggests that endocytosis by synovial cells is an important, effective mechanism controlling the synovial fluid concentration of crystals in patients with CPPD crystal deposition disease.", "contents": "CLearance of calcium pyrophosphate dihydrate crystals in vivo. II. Studies using triclinic crystals doubly labeled with 45Ca and 85Sr. The clearance rate of isotopically labeled synthetic triclinic calcium pyrophosphate dihydrate (CPPD) crystals injection into rabbit joints was estimated by serial counting. Kinetic analysis using a four compartment model showed that half of the injected dose was cleared from 4 rabbit knee joints in 19.1 +/- 0.42 (SEM) days. Profound hypomagnesemia, produced in 2 rabbits with a low magnesium diet, did not affect the rate of crystal clearance detectably. Lavage of joints with solutions known to promote CPPD crystal solubility failed to remove detectable radioactivity. The previous finding of CPPD crystals in synovial phagocytes by electron microscopy, together with the finding of nuclide activity in the synovium and the failure to remove such activity by joint lavage, suggests that endocytosis by synovial cells is an important, effective mechanism controlling the synovial fluid concentration of crystals in patients with CPPD crystal deposition disease."}
{"id": "PMID:226099", "title": "[Effects of ampicillin and cefazolin combined with mecillinam (author's transl)].", "content": "Combination effects of mecillinam + ampicillin and mecillinam + cefazolin were investigated by the cross diffusion test and by the kinetics of bactericidal action. Synergism was found by cross diffusion in about 50% of strains of E. coli, Klebsiella and Proteus. Sensitivity against ampicillin was correlated with synergism. In mecillinam-resistant strains, synergism is usually absent. The combination of ampicillin or cefazolin with mecillinam leads to bactericidal acceleration; the effects are comparable to those of the combination with gentamycin. Mecillinam seems to be a clinically promising agent for combination chemotherapy. A simple test for synergism is desirable.", "contents": "[Effects of ampicillin and cefazolin combined with mecillinam (author's transl)]. Combination effects of mecillinam + ampicillin and mecillinam + cefazolin were investigated by the cross diffusion test and by the kinetics of bactericidal action. Synergism was found by cross diffusion in about 50% of strains of E. coli, Klebsiella and Proteus. Sensitivity against ampicillin was correlated with synergism. In mecillinam-resistant strains, synergism is usually absent. The combination of ampicillin or cefazolin with mecillinam leads to bactericidal acceleration; the effects are comparable to those of the combination with gentamycin. Mecillinam seems to be a clinically promising agent for combination chemotherapy. A simple test for synergism is desirable."}
{"id": "PMID:226100", "title": "Virucidal activity of some quaternary ammonium compounds.", "content": "Four different quaternary ammonium compounds were tested by microtechniques for evaluating their activity against the type species of six viral groups very frequently involved in human and animal pathology. Three disinfectants showed good activity against five of the representative viruses under test, while the fourth proved less effective. Poliovirus type 1 was found to be completely resistant.", "contents": "Virucidal activity of some quaternary ammonium compounds. Four different quaternary ammonium compounds were tested by microtechniques for evaluating their activity against the type species of six viral groups very frequently involved in human and animal pathology. Three disinfectants showed good activity against five of the representative viruses under test, while the fourth proved less effective. Poliovirus type 1 was found to be completely resistant."}
{"id": "PMID:226101", "title": "Effect of the diuretic, 1,4-dimorpholino-7-phenylpyrido[3,4-d]-pyridazine (DS-511) and its derivatives on ADH-cyclic AMP system in rat renal medullary slices.", "content": "The effect of the diuretics, 1,4-dimorpholino-7-phenylpyrido[3,4-d]pyridazine (DS-511) and its 4'-hydroxy derivative [DS-511(4'-OH)] on the ADH-cyclic AMP system was studied in slices of rat renal medulla. These compounds alone did not affect the basal level of cyclic AMP in the slices. Preincubation with 10(-6) mol DS-511 or 10(-7) to 10(-5) mol DS-511-(4'-OH) in the presence of theophylline, inhibited arginine vasopressin stimulated formation of cyclic AMP, but after washing the slices the formation was restored. Etacrynic acid required higher concentrations such as 10(-5) and 10(4-) mol to cause inhibition. No effect was observed with furosemide and hydrochlorothiazide in concentrations up to 10(-4) mol. DS-511(4'-OH) at concentrations higher than 10(-6) mol inhibited the activity of cyclic AMP-phosphodiesterase in the medullary homogenate. These results suggest the water diuretic action of DS-511 is partly mediated by its inhibition of the ADH-cyclic AMP system.", "contents": "Effect of the diuretic, 1,4-dimorpholino-7-phenylpyrido[3,4-d]-pyridazine (DS-511) and its derivatives on ADH-cyclic AMP system in rat renal medullary slices. The effect of the diuretics, 1,4-dimorpholino-7-phenylpyrido[3,4-d]pyridazine (DS-511) and its 4'-hydroxy derivative [DS-511(4'-OH)] on the ADH-cyclic AMP system was studied in slices of rat renal medulla. These compounds alone did not affect the basal level of cyclic AMP in the slices. Preincubation with 10(-6) mol DS-511 or 10(-7) to 10(-5) mol DS-511-(4'-OH) in the presence of theophylline, inhibited arginine vasopressin stimulated formation of cyclic AMP, but after washing the slices the formation was restored. Etacrynic acid required higher concentrations such as 10(-5) and 10(4-) mol to cause inhibition. No effect was observed with furosemide and hydrochlorothiazide in concentrations up to 10(-4) mol. DS-511(4'-OH) at concentrations higher than 10(-6) mol inhibited the activity of cyclic AMP-phosphodiesterase in the medullary homogenate. These results suggest the water diuretic action of DS-511 is partly mediated by its inhibition of the ADH-cyclic AMP system."}
{"id": "PMID:226102", "title": "Phenylephrine interaction with specific red cell receptors.", "content": "An investigation of the action of phenylephrine on the transport of sodium across the human cell membrane is reported. The characteristic parameters of drug-receptor interaction -- the maximal response and ED50 -- were calculated based on the conventional dose-response plot and its linear transformations. The results obtained were in good agreement with other experimental findings.", "contents": "Phenylephrine interaction with specific red cell receptors. An investigation of the action of phenylephrine on the transport of sodium across the human cell membrane is reported. The characteristic parameters of drug-receptor interaction -- the maximal response and ED50 -- were calculated based on the conventional dose-response plot and its linear transformations. The results obtained were in good agreement with other experimental findings."}
{"id": "PMID:226103", "title": "[Effect of cyproheptadine on the regulation of the adrenal system (author's transl)].", "content": "The effect of the antiserotoninergic agent cyproheptadine (C) on the adrenal system was studied in male rats, the adrenocorticol function of which was assessed by analysis of the urinary excretion of free corticosterone. After a feeding period with 0.5--0.7 mg C/kg body weight/day for several months significant differences in the urinary excretion of free corticosterone were only found when the rats were exposed to systemic stress stimuli as cold (increase from 118.7 +/- 5.3 to 305.5 +/- 5.1 vs. 417.8 +/- 48.6 ng/d in the controls; p less than 0.001) and hunger (no increase of free corticosterone in treated animals as compared to an increase to 446.0 +/- 53.6 ng/d in the controls). In contrast to these findings no effect of C was seen when studying the neurotropic stress stimuli reserpine and ether. The same was true when measuring free corticosterone under basal conditions and after ACTH- or metyrapone stimulation. It is concluded that serotonin plays a major role as hypothalamic neurotransmitter in systemic but not in the studied neurotropic stress stimuli. The site of serotonin action does not comprise adrenal synthesis of steroids and the hypothalamic-pituitary-adrenal feedback system, as is shown by the ACTH- and metyrapone stimulation tests.", "contents": "[Effect of cyproheptadine on the regulation of the adrenal system (author's transl)]. The effect of the antiserotoninergic agent cyproheptadine (C) on the adrenal system was studied in male rats, the adrenocorticol function of which was assessed by analysis of the urinary excretion of free corticosterone. After a feeding period with 0.5--0.7 mg C/kg body weight/day for several months significant differences in the urinary excretion of free corticosterone were only found when the rats were exposed to systemic stress stimuli as cold (increase from 118.7 +/- 5.3 to 305.5 +/- 5.1 vs. 417.8 +/- 48.6 ng/d in the controls; p less than 0.001) and hunger (no increase of free corticosterone in treated animals as compared to an increase to 446.0 +/- 53.6 ng/d in the controls). In contrast to these findings no effect of C was seen when studying the neurotropic stress stimuli reserpine and ether. The same was true when measuring free corticosterone under basal conditions and after ACTH- or metyrapone stimulation. It is concluded that serotonin plays a major role as hypothalamic neurotransmitter in systemic but not in the studied neurotropic stress stimuli. The site of serotonin action does not comprise adrenal synthesis of steroids and the hypothalamic-pituitary-adrenal feedback system, as is shown by the ACTH- and metyrapone stimulation tests."}
{"id": "PMID:226104", "title": "On the biochemical mechanism of action of 1-propyl-3-methyl-7-(5-hydroxy-hexyl)-xanthine (HWA 153), a new bronchospasmolytically active methyl xanthine derivative.", "content": "1-Propyl-3-methyl-7-(5-hydroxy-hexyl)-xanthine (HWA 153) is a new bronchospasmolytic agent with a significant influence on the cAMP system of lungs and bronchi. In in vitro experiments HWA 153 inhibits cAMP phosphodiesterase (PDE) isolated from bovine bronchi more than does theophylline. HWA 153 is (in conc. 5 x 10(-4) mol/l) 1.8 and 4.3 times more active as a PDE inhibitor of guinea pig lungs and bronchi, respectively, than theophylline-ethylenediamine. HWA 153 also stabilizes rat erythrocyte membrane against hypoosmotic shock. In isolated guinea pig bronchi HWA 153 (in conc. 5 x 10(-4) mol/l) decreases by 77% bronchial spasm induced by the addition of histamine (5 x 10(-5) mol/l). A significant increase in cAMP level of bronchi was simultaneously observed. In in vivo experiments HWA 153 (25 mg/kg p.o.) inhibits PDE of lungs and bronchi of guinea pigs. Simultaneously, a significant increase in cAMP level in these organs was observed. In in vivo experiments with hypoxic rats, HWA 153 (25 mg/kg p.o.) increases ATP, ATP/ADP ratio and adenylate energy charge (AEC) in hypoxic rats, 1 h after administration. This indicates a positive influence of HWA 153 on the energy metabolism of red blood cells.", "contents": "On the biochemical mechanism of action of 1-propyl-3-methyl-7-(5-hydroxy-hexyl)-xanthine (HWA 153), a new bronchospasmolytically active methyl xanthine derivative. 1-Propyl-3-methyl-7-(5-hydroxy-hexyl)-xanthine (HWA 153) is a new bronchospasmolytic agent with a significant influence on the cAMP system of lungs and bronchi. In in vitro experiments HWA 153 inhibits cAMP phosphodiesterase (PDE) isolated from bovine bronchi more than does theophylline. HWA 153 is (in conc. 5 x 10(-4) mol/l) 1.8 and 4.3 times more active as a PDE inhibitor of guinea pig lungs and bronchi, respectively, than theophylline-ethylenediamine. HWA 153 also stabilizes rat erythrocyte membrane against hypoosmotic shock. In isolated guinea pig bronchi HWA 153 (in conc. 5 x 10(-4) mol/l) decreases by 77% bronchial spasm induced by the addition of histamine (5 x 10(-5) mol/l). A significant increase in cAMP level of bronchi was simultaneously observed. In in vivo experiments HWA 153 (25 mg/kg p.o.) inhibits PDE of lungs and bronchi of guinea pigs. Simultaneously, a significant increase in cAMP level in these organs was observed. In in vivo experiments with hypoxic rats, HWA 153 (25 mg/kg p.o.) increases ATP, ATP/ADP ratio and adenylate energy charge (AEC) in hypoxic rats, 1 h after administration. This indicates a positive influence of HWA 153 on the energy metabolism of red blood cells."}
{"id": "PMID:226105", "title": "The effect of cholestyramine on lipoprotein lipids in patients with primary type IIA hyperlipoproteinemia.", "content": "The effect of 3 months' treatment with cholestyramine on lipoprotein lipids was investigated in 12 patients. VLDL, LDL and HDL were separated by preparative ultracentrifugation. There was a significant decrease of serum cholesterol and phospholipids and an increase of serum triglycerides. All the VLDL-lipids increased by nearly 30%. The LDL-lipids decreased with a tendency for normalisation of their atypical lipid composition. The small but significant alterations of HDL triglycerides and cholesterol are correlated with the corresponding alterations of the other lipoproteins; the HDL-phospholipids were unchanged. The LDL/HDL-lipid ratios were decreased but not normalised. The 30% decrease of LDL-cholesterol is negatively correlated with an increase in all the VLDL-lipids.", "contents": "The effect of cholestyramine on lipoprotein lipids in patients with primary type IIA hyperlipoproteinemia. The effect of 3 months' treatment with cholestyramine on lipoprotein lipids was investigated in 12 patients. VLDL, LDL and HDL were separated by preparative ultracentrifugation. There was a significant decrease of serum cholesterol and phospholipids and an increase of serum triglycerides. All the VLDL-lipids increased by nearly 30%. The LDL-lipids decreased with a tendency for normalisation of their atypical lipid composition. The small but significant alterations of HDL triglycerides and cholesterol are correlated with the corresponding alterations of the other lipoproteins; the HDL-phospholipids were unchanged. The LDL/HDL-lipid ratios were decreased but not normalised. The 30% decrease of LDL-cholesterol is negatively correlated with an increase in all the VLDL-lipids."}
{"id": "PMID:226106", "title": "Effects of dipyridamole in experimental atherosclerosis. Action on PGI2, platelet aggregation and atherosclerotic plaque formation.", "content": "Experimental atherosclerosis in rabbits induced by feeding a standard atherogenic diet for 4 months resulted in an increased sensitivity of platelets to the proaggregatory action of collagen and ADP. Treatment with dipyridamole (3 x 10 mg/day i.m.) for 4 weeks normalized platelet loss in atherosclerotic rabbits and abolished the increased sensitivity to proaggregatory collagen, but not to ADP. Dipyridamole treatment lowered basal as well as PGI2-induced cAMP levels below values seen in platelets from normal rabbits, but the stimulation by PGI2 relative to basal cAMP levels was not affected or even increased by dipyridamole treatment. Dipyridamole did not affect the increased sensitivity of platelets from atherosclerotic rabbits to the antiaggregatory action of PGI2, indicating that dipyridamole decreased absolute cAMP levels, probably due to reduction of the adenine nucleotide pool in platelets without affecting the adenylate cyclase function. Dipyridamole enhanced atherosclerotic plaque formation in arterial walls. Basal as well as PGI2-stimulated cAMP content was lower in homogenates from atherosclerotic than from normal aortic tissue. Dipyridamole-treated animals showed a further decrease in basal as well as PGI2-stimulated cAMP content of the aortic tissue, suggesting that this decrease in cAMP content may be linked to the enhanced proliferative activity seen in artherosclerotic plaque formation.", "contents": "Effects of dipyridamole in experimental atherosclerosis. Action on PGI2, platelet aggregation and atherosclerotic plaque formation. Experimental atherosclerosis in rabbits induced by feeding a standard atherogenic diet for 4 months resulted in an increased sensitivity of platelets to the proaggregatory action of collagen and ADP. Treatment with dipyridamole (3 x 10 mg/day i.m.) for 4 weeks normalized platelet loss in atherosclerotic rabbits and abolished the increased sensitivity to proaggregatory collagen, but not to ADP. Dipyridamole treatment lowered basal as well as PGI2-induced cAMP levels below values seen in platelets from normal rabbits, but the stimulation by PGI2 relative to basal cAMP levels was not affected or even increased by dipyridamole treatment. Dipyridamole did not affect the increased sensitivity of platelets from atherosclerotic rabbits to the antiaggregatory action of PGI2, indicating that dipyridamole decreased absolute cAMP levels, probably due to reduction of the adenine nucleotide pool in platelets without affecting the adenylate cyclase function. Dipyridamole enhanced atherosclerotic plaque formation in arterial walls. Basal as well as PGI2-stimulated cAMP content was lower in homogenates from atherosclerotic than from normal aortic tissue. Dipyridamole-treated animals showed a further decrease in basal as well as PGI2-stimulated cAMP content of the aortic tissue, suggesting that this decrease in cAMP content may be linked to the enhanced proliferative activity seen in artherosclerotic plaque formation."}
{"id": "PMID:226107", "title": "Characterization of free and tightly bound lipoprotein in intima by thin layer isoelectric focusing.", "content": "Thin layer isoelectric focusing followed by second dimension quantitative immunoelectrophoresis has been used to characterize the free and tightly bound lipoprotein (lp) fractions in human aortic intima. In 3.3% acrylamide gels plasma low density lipoprotein (LDL) focuses rapidly, but very low density lipoprotein (VLDL) fails to enter the gell and remains at the origin (point of application). Samples of normal intima and lesions were placed directly on the gel and focused for 10--12 h; in normal intima and gelatinous lesions which had not accumulated cholesterol 60--70% of the free LP focused with plasma LDL, but with increasing accumulation of cholesterol the proportion focusing with LDL decreased and the component remaining at the origin increased. In 9 of the 39 samples examined one or more components with pI acid to LDL were present, and in one sample the whole peak focused at a more acid pI. In 4 of 5 lipid-rich centres of gelatinous plaques all the free LP remained at the origin, and the bound LP released by incubation with plasmin remained at the origin in all samples in 3.3% gels although it would focus in 2.6% gels. With antiserum to apo-C  this large LP did not behave like VLDL, and it appears to be an aggregated LDL. An increased proportion of aggregated LDL was associated with (a) accumulation of cholesterol, (b) topographical location towards the centre of plaques, and (c) partial destruction of endogenous LP during incubation of fresh samples of tissue.", "contents": "Characterization of free and tightly bound lipoprotein in intima by thin layer isoelectric focusing. Thin layer isoelectric focusing followed by second dimension quantitative immunoelectrophoresis has been used to characterize the free and tightly bound lipoprotein (lp) fractions in human aortic intima. In 3.3% acrylamide gels plasma low density lipoprotein (LDL) focuses rapidly, but very low density lipoprotein (VLDL) fails to enter the gell and remains at the origin (point of application). Samples of normal intima and lesions were placed directly on the gel and focused for 10--12 h; in normal intima and gelatinous lesions which had not accumulated cholesterol 60--70% of the free LP focused with plasma LDL, but with increasing accumulation of cholesterol the proportion focusing with LDL decreased and the component remaining at the origin increased. In 9 of the 39 samples examined one or more components with pI acid to LDL were present, and in one sample the whole peak focused at a more acid pI. In 4 of 5 lipid-rich centres of gelatinous plaques all the free LP remained at the origin, and the bound LP released by incubation with plasmin remained at the origin in all samples in 3.3% gels although it would focus in 2.6% gels. With antiserum to apo-C  this large LP did not behave like VLDL, and it appears to be an aggregated LDL. An increased proportion of aggregated LDL was associated with (a) accumulation of cholesterol, (b) topographical location towards the centre of plaques, and (c) partial destruction of endogenous LP during incubation of fresh samples of tissue."}
{"id": "PMID:226108", "title": "Regulation of cholesterol synthesis in skin fibroblasts derived from old people.", "content": "Sterol synthesis from radioactive acetate and the suppression of this synthesis by human low density lipoprotein (LDL) have been investigated in skin fibroblast strains derived from infant donors and from donors over the age of 70 years. The activity of the enzyme hydroxymethylglutaryl-CoA reductase and its repression by LDL has also been investigated in these fibroblast strains and in senescent cells of the foetal lung cell strain MRC-5. No age-related differences could be detected either in repression of [3H]acetate incorporation by LDL, or in repression of HMG-CoA reductase activity.", "contents": "Regulation of cholesterol synthesis in skin fibroblasts derived from old people. Sterol synthesis from radioactive acetate and the suppression of this synthesis by human low density lipoprotein (LDL) have been investigated in skin fibroblast strains derived from infant donors and from donors over the age of 70 years. The activity of the enzyme hydroxymethylglutaryl-CoA reductase and its repression by LDL has also been investigated in these fibroblast strains and in senescent cells of the foetal lung cell strain MRC-5. No age-related differences could be detected either in repression of [3H]acetate incorporation by LDL, or in repression of HMG-CoA reductase activity."}
{"id": "PMID:226109", "title": "High density lipoprotein levels in children of young men with ischaemic heart disease.", "content": "This study was designed to assess HDL levels in children of young men with IHD, compared with children of asymptomatic men. Like their fathers, sons of patients with heart disease, had significantly lower HDL cholesterols than controls. This difference was independent of fasting triglycerides, obesity, diet or physical activity, and was the only \"coronary risk factor\" in this young age group.", "contents": "High density lipoprotein levels in children of young men with ischaemic heart disease. This study was designed to assess HDL levels in children of young men with IHD, compared with children of asymptomatic men. Like their fathers, sons of patients with heart disease, had significantly lower HDL cholesterols than controls. This difference was independent of fasting triglycerides, obesity, diet or physical activity, and was the only \"coronary risk factor\" in this young age group."}
{"id": "PMID:226113", "title": "Virus-specific and anticellular antibodies in molluscum contagiosum.", "content": "Sera from patients with molluscum contagiosum showed a higher incidence of anticellular and fibrillar anticellular antibodies of IgM class as compared to sera from control subjects. Most patients with anticellular IgM antibodies also had molluscum contagiosum virus-specific antibodies. In a comparative study, there was a higher incidence of anticellular IgM antibodies to normal human epidermis and fibrillar anticellular IgM antibodies in molluscum contagiosum than in warts of psoriasis. The incidence in psoriasis was lower than warts and was similar to that found in control subjects.", "contents": "Virus-specific and anticellular antibodies in molluscum contagiosum. Sera from patients with molluscum contagiosum showed a higher incidence of anticellular and fibrillar anticellular antibodies of IgM class as compared to sera from control subjects. Most patients with anticellular IgM antibodies also had molluscum contagiosum virus-specific antibodies. In a comparative study, there was a higher incidence of anticellular IgM antibodies to normal human epidermis and fibrillar anticellular IgM antibodies in molluscum contagiosum than in warts of psoriasis. The incidence in psoriasis was lower than warts and was similar to that found in control subjects."}
{"id": "PMID:226110", "title": "[Association of Wilms' tumor, pseudohermaphroditism and glomerular nephropathy. Partial and complete forms of the syndrome].", "content": "Four patients, followed at the Buenos Aires Cildren's Hospital are reported: one with a nephrotic syndrome and male pseudohermaphroditism, the second with nephrotic syndrome, male pseudohermaphroditism and Wilms' tumor, the third with pseudohermaphroditism and Wilms' tumor and the fourth with a nephrotic syndrome and Wilms' tumor. The cases presenting nephrotic syndrome, all had an early onset and a rapid and fatal course leading to death in renal failure or secondary to a related bacterial infection. The renal histology in all of the cases with nephrotic syndrome, was very similar: diffuse involvement of all glomeruli consisting in a severe increase of the mesangial matrix, with scarce mesengial proliferation.", "contents": "[Association of Wilms' tumor, pseudohermaphroditism and glomerular nephropathy. Partial and complete forms of the syndrome]. Four patients, followed at the Buenos Aires Cildren's Hospital are reported: one with a nephrotic syndrome and male pseudohermaphroditism, the second with nephrotic syndrome, male pseudohermaphroditism and Wilms' tumor, the third with pseudohermaphroditism and Wilms' tumor and the fourth with a nephrotic syndrome and Wilms' tumor. The cases presenting nephrotic syndrome, all had an early onset and a rapid and fatal course leading to death in renal failure or secondary to a related bacterial infection. The renal histology in all of the cases with nephrotic syndrome, was very similar: diffuse involvement of all glomeruli consisting in a severe increase of the mesangial matrix, with scarce mesengial proliferation."}
{"id": "PMID:226114", "title": "Comparative sensitivity of a cultural test and the complement fixation test in the diagnosis of adenovirus ocular infection.", "content": "The sensitivity of human embryonic kidney (HEK) cell culture and the complement fixation test (cft) in the diagnosis of adenovirus ocular infection has been compared. The optimum time for collection of specimens to obtain the best results by each test has been examined. Sixty-one (53%) of 116 patients with moderate to severe follicular conjunctivitis, clinically indicative of adenovirus infection, had serological evidence of infection or had the virus isolated from ocular swabs. Virus was isolated from 53 patients (45%) and significant antibody rises were found in 33 (27%). When each test was carried out under optimum conditions, virus was isolated from 82% of cases and serological evidence of infection found in 72%. Serological responses as detected by the CFT appeared to be inferior in infections caused by adenovirus type 7 to those encountered in infections due to adenovirus types 3 and 8.", "contents": "Comparative sensitivity of a cultural test and the complement fixation test in the diagnosis of adenovirus ocular infection. The sensitivity of human embryonic kidney (HEK) cell culture and the complement fixation test (cft) in the diagnosis of adenovirus ocular infection has been compared. The optimum time for collection of specimens to obtain the best results by each test has been examined. Sixty-one (53%) of 116 patients with moderate to severe follicular conjunctivitis, clinically indicative of adenovirus infection, had serological evidence of infection or had the virus isolated from ocular swabs. Virus was isolated from 53 patients (45%) and significant antibody rises were found in 33 (27%). When each test was carried out under optimum conditions, virus was isolated from 82% of cases and serological evidence of infection found in 72%. Serological responses as detected by the CFT appeared to be inferior in infections caused by adenovirus type 7 to those encountered in infections due to adenovirus types 3 and 8."}
{"id": "PMID:226116", "title": "Kinetics of hydrogen-deuterium exchange in guanosine 5'-monophosphate and guanosine 3':5'-monophosphate determined by laser-Raman spectroscopy.", "content": "Pseudo-first-order rate constants governing the deuterium exchange of 8-CH groups in guanosine 5'-monophosphate (5'-rGMP) and guanosine 3':5'-monophosphate (cGMP) were determined as a function of temperature in the range 30-80 degrees C by means of laser-Raman spectroscopy. For each guanine nucleotide the logarithm of the rate constant exhibits a strictly linear dependence on reciprocal temperature: i.e., k psi = Ae-Ea/RT with A = 8.84 X 10(14) h-1 and Ea = 24.6 kcal/mol for 5'-rGMP and A = 3.33 X 10(13) h-1 and Ea = 22.2 kcal/mol for cGMP. Exchange of the 8-CH groups in guanine nucleotides is generally 2-3 times more rapid than in adenine nucleotides [cf. g. j. thomas, Jr., & J. Livramento (1975) Biochemistry 14, 5210-5218]. As in the case of adenine nucleotides, cyclic and 5' nucleotides of guanine exchange at markedly different rates at lower temperatures, with exchange in the cyclic nucleotide being the more facile. Each of the guanine nucleotides was prepared in four different isotopic modifications for Raman spectral analysis. The Raman frequency shifts resulting from the various isotopic substitutions have been tabulated, and assignments have been given for most of the observed vibrational frequencies.", "contents": "Kinetics of hydrogen-deuterium exchange in guanosine 5'-monophosphate and guanosine 3':5'-monophosphate determined by laser-Raman spectroscopy. Pseudo-first-order rate constants governing the deuterium exchange of 8-CH groups in guanosine 5'-monophosphate (5'-rGMP) and guanosine 3':5'-monophosphate (cGMP) were determined as a function of temperature in the range 30-80 degrees C by means of laser-Raman spectroscopy. For each guanine nucleotide the logarithm of the rate constant exhibits a strictly linear dependence on reciprocal temperature: i.e., k psi = Ae-Ea/RT with A = 8.84 X 10(14) h-1 and Ea = 24.6 kcal/mol for 5'-rGMP and A = 3.33 X 10(13) h-1 and Ea = 22.2 kcal/mol for cGMP. Exchange of the 8-CH groups in guanine nucleotides is generally 2-3 times more rapid than in adenine nucleotides [cf. g. j. thomas, Jr., & J. Livramento (1975) Biochemistry 14, 5210-5218]. As in the case of adenine nucleotides, cyclic and 5' nucleotides of guanine exchange at markedly different rates at lower temperatures, with exchange in the cyclic nucleotide being the more facile. Each of the guanine nucleotides was prepared in four different isotopic modifications for Raman spectral analysis. The Raman frequency shifts resulting from the various isotopic substitutions have been tabulated, and assignments have been given for most of the observed vibrational frequencies."}
{"id": "PMID:226115", "title": "An outbreak of adenovirus keratoconjunctivitis in bristol.", "content": "Nineteen cases of keratoconjunctivitis caused by an adenovirus serologically related to types 10 and 19 are described. Seventeen of the patients presented over a period of 7 weeks and included 4 who were involved in a minor outbreak at a factory. The presentation and clinical features closely resembled those caused by adenoviruses types 8 and 19. Mild to severe follicular conjunctivitis, superficial punctate keratitis, discrete subepithelial opacities, membrane formation, and conjunctival scarring were all observed.", "contents": "An outbreak of adenovirus keratoconjunctivitis in bristol. Nineteen cases of keratoconjunctivitis caused by an adenovirus serologically related to types 10 and 19 are described. Seventeen of the patients presented over a period of 7 weeks and included 4 who were involved in a minor outbreak at a factory. The presentation and clinical features closely resembled those caused by adenoviruses types 8 and 19. Mild to severe follicular conjunctivitis, superficial punctate keratitis, discrete subepithelial opacities, membrane formation, and conjunctival scarring were all observed."}
{"id": "PMID:226117", "title": "Oxidation of (horse) hemoglobin by copper: an intermediate detected by electron spin resonance.", "content": "The oxidation of horse hemoglobin by Cu(II) has been followed by the changes in the electron spin resonance spectra of copper. By stopped-flow and freeze-quenching techniques, it is shown that the second-order rate constant for the binding of Cu(II) to hemoglobin is greater than 5 X 10(5) mol-1 s-1 and the apparent first-order rate for the reduction of Cu(II) to Cu(I) is 0.051 s-1. It is also shown that the binding of Cu(II) to hemoglobin is followed by an alteration of the Cu(II) spectrum, decreasing the g values. This process has an apparent rate constant of 17 s-1 and presumably involves a conformational change in the region of the copper binding site. It is also shown that this conformational change is apparently necessary for Cu(II) to oxidize hemoglobin.", "contents": "Oxidation of (horse) hemoglobin by copper: an intermediate detected by electron spin resonance. The oxidation of horse hemoglobin by Cu(II) has been followed by the changes in the electron spin resonance spectra of copper. By stopped-flow and freeze-quenching techniques, it is shown that the second-order rate constant for the binding of Cu(II) to hemoglobin is greater than 5 X 10(5) mol-1 s-1 and the apparent first-order rate for the reduction of Cu(II) to Cu(I) is 0.051 s-1. It is also shown that the binding of Cu(II) to hemoglobin is followed by an alteration of the Cu(II) spectrum, decreasing the g values. This process has an apparent rate constant of 17 s-1 and presumably involves a conformational change in the region of the copper binding site. It is also shown that this conformational change is apparently necessary for Cu(II) to oxidize hemoglobin."}
{"id": "PMID:226118", "title": "Implications of the integrated rate law for the reactions of Paracoccus denitrificans nitrite reductase.", "content": "The integrated rate law for the reaction of the nitrite reductase of Paracoccus denitrificans, a cytochrome cd, has been established for turnover assays using donor ferrocytochromes c and either nitrite or molecular oxygen as the ultimate acceptor. The time course for the concentration of ferrocytochrome follows the law: formula: (see text), where S is the concentration of donor ferrocytochrome c, So is the initial concentration, t is time, and u1, u2, and u3 are empirical parameters that are constant for a given experiment but depend upon the initial substrate concentration. In particular, all the u1 increase with decreasing initial ferrocytochrome concentration. Saturation of reaction rates at high donor ferrocytochrome concentrations was not observed. The parameter u1 was proportional to the enzyme concentration while u2 and u3 were not. The form of the integrated rate law and the behavior of the u1 impose severe restrictions on possible kinetic schemes for the activity of the enzyme. Contemporary mechanisms that have been proposed for mitochondrial oxidase aa3 are examined and found to be inadequate to explain the reactivity of cytochrome cd. The simplest interpretations of the cytochrome cd data suggest that the enzyme does not bind the ferri and ferro forms of donor cytochromes c with equal affinity and that the enzyme is subject to inhibition by a product of reaction. Eucaryotic horse cytochrome c reacts with the Paracoccus cytochrome cd with 77% of the activity when Paracoccus cytochrome c550 is used as the electron donor.", "contents": "Implications of the integrated rate law for the reactions of Paracoccus denitrificans nitrite reductase. The integrated rate law for the reaction of the nitrite reductase of Paracoccus denitrificans, a cytochrome cd, has been established for turnover assays using donor ferrocytochromes c and either nitrite or molecular oxygen as the ultimate acceptor. The time course for the concentration of ferrocytochrome follows the law: formula: (see text), where S is the concentration of donor ferrocytochrome c, So is the initial concentration, t is time, and u1, u2, and u3 are empirical parameters that are constant for a given experiment but depend upon the initial substrate concentration. In particular, all the u1 increase with decreasing initial ferrocytochrome concentration. Saturation of reaction rates at high donor ferrocytochrome concentrations was not observed. The parameter u1 was proportional to the enzyme concentration while u2 and u3 were not. The form of the integrated rate law and the behavior of the u1 impose severe restrictions on possible kinetic schemes for the activity of the enzyme. Contemporary mechanisms that have been proposed for mitochondrial oxidase aa3 are examined and found to be inadequate to explain the reactivity of cytochrome cd. The simplest interpretations of the cytochrome cd data suggest that the enzyme does not bind the ferri and ferro forms of donor cytochromes c with equal affinity and that the enzyme is subject to inhibition by a product of reaction. Eucaryotic horse cytochrome c reacts with the Paracoccus cytochrome cd with 77% of the activity when Paracoccus cytochrome c550 is used as the electron donor."}
{"id": "PMID:226119", "title": "Stereochemical course of phosphokinases. The use of adenosine [gamma-(S)-16O,17O,18O]triphosphate and the mechanistic consequences for the reactions catalyzed by glycerol kinase, hexokinase, pyruvate kinase, and acetate kinase.", "content": "We report the synthesis of adenosine [gamma-(S)-16O,17O,18O]triphosphate, an isotopically labeled species of ATP that is chiral at the gamma-phosphoryl group, the configuration of which has been confirmed by independent stereochemical analysis. This molecule has been used as a substrate in the reactions catalyzed by glycerol kinase and by acetate kinase. The resulting samples of isotopically labeled sn-glycerol 3-phosphate and of acetyl phosphate have been used as substrates in the alkaline phosphatase mediated transfer of the chiral phosphoryl groups to (S)-propane-1,2-diol, whence the configuration at phosphorus has been determined [Abbott, S. J., Jones, S. R., Weinman, S. A., & Knowles, J. R. (1978) J. Am. Chem. Soc. 100, 2558]. It is shown that glycerol kinase and acetate kinase (and, by virtue of an earlier correlation, pyruvate kinase and hexokinase) proceed by pathways that result in inversion of the configuration at phosphorus. The sterochemical approach provides an access to the otherwise cryptic events that are involved in phosphoryl-group transfer within the ternary complexes of these kinases and their substrates.", "contents": "Stereochemical course of phosphokinases. The use of adenosine [gamma-(S)-16O,17O,18O]triphosphate and the mechanistic consequences for the reactions catalyzed by glycerol kinase, hexokinase, pyruvate kinase, and acetate kinase. We report the synthesis of adenosine [gamma-(S)-16O,17O,18O]triphosphate, an isotopically labeled species of ATP that is chiral at the gamma-phosphoryl group, the configuration of which has been confirmed by independent stereochemical analysis. This molecule has been used as a substrate in the reactions catalyzed by glycerol kinase and by acetate kinase. The resulting samples of isotopically labeled sn-glycerol 3-phosphate and of acetyl phosphate have been used as substrates in the alkaline phosphatase mediated transfer of the chiral phosphoryl groups to (S)-propane-1,2-diol, whence the configuration at phosphorus has been determined [Abbott, S. J., Jones, S. R., Weinman, S. A., & Knowles, J. R. (1978) J. Am. Chem. Soc. 100, 2558]. It is shown that glycerol kinase and acetate kinase (and, by virtue of an earlier correlation, pyruvate kinase and hexokinase) proceed by pathways that result in inversion of the configuration at phosphorus. The sterochemical approach provides an access to the otherwise cryptic events that are involved in phosphoryl-group transfer within the ternary complexes of these kinases and their substrates."}
{"id": "PMID:226121", "title": "Mechanistic studies on deoxyribonucleic acid dependent ribonucleic acid polymerase from Escherichia coli using phosphorothioate analogues. 1. Initiation and pyrophosphate exchange reactions.", "content": "The diastereomers of adenosine 5'-O-(1-thiotriphosphate) (ATP alpha S) and adenosine 5'-O-(2-thiotriphosphate) (ATP beta S) can replace adenosine triphosphate (ATP) in the initiation reaction catalyzed by deoxyribonucleic acid (DNA) dependent ribonucleic acid (RNA) polymerase from Escherichia coli. In both cases, the Sp diastereomer is a better initiator than the Rp isomer. The diasteromers of 3'-uridyl 5'-adenosyl ,O-phosphorothioate [Up(S)A] can replace UpA in the primed initiation reaction catalyzed by RNA polymerase; however, the Rp diastereomer is a better initiator than the Sp isomer. By using ATP or CpA as initiator and UTP alpha S, isomer A, as substrate, we determined the stereochemical courses of both the initiation and primed initiation reactions, respectively, with T7 DNA template and found them to proceed with inversion of configuration. Determination of the stereochemical course of the pyrophosphate exchange reaction catalyzed by RNA polymerase provides evidence that this reaction is the reverse of the phosphodiester bond-forming reaction.", "contents": "Mechanistic studies on deoxyribonucleic acid dependent ribonucleic acid polymerase from Escherichia coli using phosphorothioate analogues. 1. Initiation and pyrophosphate exchange reactions. The diastereomers of adenosine 5'-O-(1-thiotriphosphate) (ATP alpha S) and adenosine 5'-O-(2-thiotriphosphate) (ATP beta S) can replace adenosine triphosphate (ATP) in the initiation reaction catalyzed by deoxyribonucleic acid (DNA) dependent ribonucleic acid (RNA) polymerase from Escherichia coli. In both cases, the Sp diastereomer is a better initiator than the Rp isomer. The diasteromers of 3'-uridyl 5'-adenosyl ,O-phosphorothioate [Up(S)A] can replace UpA in the primed initiation reaction catalyzed by RNA polymerase; however, the Rp diastereomer is a better initiator than the Sp isomer. By using ATP or CpA as initiator and UTP alpha S, isomer A, as substrate, we determined the stereochemical courses of both the initiation and primed initiation reactions, respectively, with T7 DNA template and found them to proceed with inversion of configuration. Determination of the stereochemical course of the pyrophosphate exchange reaction catalyzed by RNA polymerase provides evidence that this reaction is the reverse of the phosphodiester bond-forming reaction."}
{"id": "PMID:226122", "title": "Steroidogenic activity of high molecular weight forms of corticotropin.", "content": "The high molecular weight forms of adrenocorticotropic hormone (ACTH) produced by mouse pituitary tumor cells (AtT-20/D-16v) were separated from each other by gel filtration; their ability to stimulate steroidogenesis by isolated rat adrenal cortical cells was studied. Pools of pro-ACTH/endorphin. ACTH biosynthetic intermediate, and glycosylated ACTH(1--39) were obtained; on the basis of NaDodSO4-polyacrylamide gel electrophoresis, over 97% of the immunoactive ACTH was found to have the expected molecular weight. Suspension of isolated rat adrenal cortical cells were incubated overnight in tissue culture medium and used in a 2-h steroid production assay. Synthetic human ACTH(1--39) [hACTH(1--39)] was used as a bioassay and immunoassay standard; 60 pM hACTH(1--39) stimulated half-maximal production of fluoregenic steroid. The amount of pro-ACTH/endorphin, ACTH biosynthetic intermediate, or glycosylated (ACTH(1--39) added was estimated with an ACTH(17--24) immunoassay. All three high molecular weight forms of ACTH are capable of stimulating the same maximal level of steroidogenesis as hACTH(1--39). Glycosylated ACTH(1--39) is equipotent with hACTH(1--39); ACTH biosynthetic intermediate and pro-ACTH/endorphin are, respectively, 100- and 300-fold less potent than hACTH(1--39). Steroid production in response to all four forms of ACTH is linear in time. All of the different forms of ACTH stimulate the synthesis of corticosterone and related steroids; no significant production of cortisol or aldosterone was observed. beta-Lipotropin (beta LPH) and 16K fragment, which comprise the non-ACTH regions of pro-ACTH/endorphin and are secreted by the pituitary tumor cells, did not stimulate or interfere with steroidogenesis. Brief incubations of pro-ACTH/endorphin and ACTH biosynthetic intermediate with trypsin generated lower molecular weight forms of ACTH and increased biological activity 50-fold; thus, the decreased steroidogenic potency of these forms of ACTH is thought to be due to structural constraints on the ACTH(1--39)-like sequence in these larger precursor molecules", "contents": "Steroidogenic activity of high molecular weight forms of corticotropin. The high molecular weight forms of adrenocorticotropic hormone (ACTH) produced by mouse pituitary tumor cells (AtT-20/D-16v) were separated from each other by gel filtration; their ability to stimulate steroidogenesis by isolated rat adrenal cortical cells was studied. Pools of pro-ACTH/endorphin. ACTH biosynthetic intermediate, and glycosylated ACTH(1--39) were obtained; on the basis of NaDodSO4-polyacrylamide gel electrophoresis, over 97% of the immunoactive ACTH was found to have the expected molecular weight. Suspension of isolated rat adrenal cortical cells were incubated overnight in tissue culture medium and used in a 2-h steroid production assay. Synthetic human ACTH(1--39) [hACTH(1--39)] was used as a bioassay and immunoassay standard; 60 pM hACTH(1--39) stimulated half-maximal production of fluoregenic steroid. The amount of pro-ACTH/endorphin, ACTH biosynthetic intermediate, or glycosylated (ACTH(1--39) added was estimated with an ACTH(17--24) immunoassay. All three high molecular weight forms of ACTH are capable of stimulating the same maximal level of steroidogenesis as hACTH(1--39). Glycosylated ACTH(1--39) is equipotent with hACTH(1--39); ACTH biosynthetic intermediate and pro-ACTH/endorphin are, respectively, 100- and 300-fold less potent than hACTH(1--39). Steroid production in response to all four forms of ACTH is linear in time. All of the different forms of ACTH stimulate the synthesis of corticosterone and related steroids; no significant production of cortisol or aldosterone was observed. beta-Lipotropin (beta LPH) and 16K fragment, which comprise the non-ACTH regions of pro-ACTH/endorphin and are secreted by the pituitary tumor cells, did not stimulate or interfere with steroidogenesis. Brief incubations of pro-ACTH/endorphin and ACTH biosynthetic intermediate with trypsin generated lower molecular weight forms of ACTH and increased biological activity 50-fold; thus, the decreased steroidogenic potency of these forms of ACTH is thought to be due to structural constraints on the ACTH(1--39)-like sequence in these larger precursor molecules"}
{"id": "PMID:226124", "title": "Copper(II) protoporphyrin IX as a reporter group for the heme environment in myoglobin.", "content": "Copper(II) protoporphyrin IX has been introduced into apomyoglobin, and its utility as a reporter group of the heme environment has been examined. The Soret and visible absorption bands and electron spin resonance spectrum show that the Cu(II) is five coordinate, probably through coordination to the F-8 proximal histidine. The resonance Raman spectrum does not indicate any appreciable distortion from the solution conformation of copper(II) protoporphyrin IX dimethyl ester in CS2. The ultraviolet circular dichroism shows no alteration of the helical content of the globin from that of metmyoglobin. The circular dichroism of the porphyrin transitions suggests that the packing of the amino acid side chains around the porphyrin is different than that in the native metmyoglobin.", "contents": "Copper(II) protoporphyrin IX as a reporter group for the heme environment in myoglobin. Copper(II) protoporphyrin IX has been introduced into apomyoglobin, and its utility as a reporter group of the heme environment has been examined. The Soret and visible absorption bands and electron spin resonance spectrum show that the Cu(II) is five coordinate, probably through coordination to the F-8 proximal histidine. The resonance Raman spectrum does not indicate any appreciable distortion from the solution conformation of copper(II) protoporphyrin IX dimethyl ester in CS2. The ultraviolet circular dichroism shows no alteration of the helical content of the globin from that of metmyoglobin. The circular dichroism of the porphyrin transitions suggests that the packing of the amino acid side chains around the porphyrin is different than that in the native metmyoglobin."}
{"id": "PMID:226125", "title": "Resonance Raman spectra of cytochrome c oxidase. Excitation in the 600-nm region.", "content": "The resonance Raman (RR) spectra of oxidized, reduced, and oxidized cyanide-bound cytochrome c oxidase with excitation at several wavelengths in the 600-nm region are presented. No evidence is found for laser-induced photoreduction of the oxidized protein with irradiation at lambda approximately 600 nm at 195 K, in contrast to the predominance of this process upon irradiation in the Soret region at this temperature. The Raman spectra of all three protein species are very similar, and there are no Raman bands which are readily assignable to either cytochrome a or cytochrome a3 exclusively. The Raman spectra of the three protein species do, however, exhibit a number of bands not observed in the RR spectra of other hemoproteins upon exicitation in their visible absorption bands. In particular, strong Raman bands are observed in the low-frequency region of the RR spectra (less than 500 cm-1). The frequencies of these bands are similar to those of the copper-ligand vibrations observed in the RR spectra of type 1 copper proteins upon excitation in the 600-nm absorption band characteristic of these proteins. In cytochrome c oxidase, these bands do not disappear upon reduction of the protein and, therefore, cannot be attributed to copper-ligand vibrations. Thus, all the observed RR bands are associated with the two heme A moieties in the enzyme.", "contents": "Resonance Raman spectra of cytochrome c oxidase. Excitation in the 600-nm region. The resonance Raman (RR) spectra of oxidized, reduced, and oxidized cyanide-bound cytochrome c oxidase with excitation at several wavelengths in the 600-nm region are presented. No evidence is found for laser-induced photoreduction of the oxidized protein with irradiation at lambda approximately 600 nm at 195 K, in contrast to the predominance of this process upon irradiation in the Soret region at this temperature. The Raman spectra of all three protein species are very similar, and there are no Raman bands which are readily assignable to either cytochrome a or cytochrome a3 exclusively. The Raman spectra of the three protein species do, however, exhibit a number of bands not observed in the RR spectra of other hemoproteins upon exicitation in their visible absorption bands. In particular, strong Raman bands are observed in the low-frequency region of the RR spectra (less than 500 cm-1). The frequencies of these bands are similar to those of the copper-ligand vibrations observed in the RR spectra of type 1 copper proteins upon excitation in the 600-nm absorption band characteristic of these proteins. In cytochrome c oxidase, these bands do not disappear upon reduction of the protein and, therefore, cannot be attributed to copper-ligand vibrations. Thus, all the observed RR bands are associated with the two heme A moieties in the enzyme."}
{"id": "PMID:226127", "title": "Involvement of eucaryotic deoxyribonucleic acid polymerases alpha and gamma in the replication of cellular and viral deoxyribonucleic acid.", "content": "In an effort to identify the deoxyribonucleic acid (DNA) polymerase activities responsible for mammalian viral and cellular DNA replication, the effect of DNA synthesis inhibitors on isolated DNA polymerases was compared with their effects on viral and cellular DNA replication in vitro. DNA polymerase alpha, simian virus 40 (SV40) DNA replication in nuclear extracts, and CV-1 cell (the host for SV40) DNA replication in isolated nuclei all responded to DNA synthesis inhibitors in a quantitatively similar manner: they were relatively insensitive to 2',3'-dideoxythymidine 5'-triphosphate (d2TTP), but completely inhibited by aphidicolin, 1-beta-D-arabinofuranosylcytosine 5'-triphosphate (araCTP), and N-ethylmaleimide. In comparison, DNA polymerases beta and gamma were inhibited by d2TTP but insensitive to aphidicolin and 20--30 times less sensitive to araCTP than DNA polymerase alpha. Herpes simplex virus type 1 (HSV-1) DNA polymerase and DNA polymerase alpha were the only enzymes tested that were relatively insensitive to d2TTP; DNA polymerases beta and gamma, phage T4 and T7 DNA polymerases, and Escherichia coli DNA polymerase I were 100--250 times more sensitive. The results with d2TTP were independent of enzyme concentration, primer-template concentration, primer-template choice, and the labeled dNTP. A specific requirement for DNA polymerase alpha in the replication of SV40 DNA was demonstrated by the fact that DNA polymerase alpha was required, in addition to other cytosol proteins, to reconstitute SV40 DNA replication activity in N-ethylmaleimide-inactivated nuclear extracts containing replicating SV40 chromosomes. DNA polymerases beta and gamma did not substitute for DNA polymerase alpha. In contrast to  SV40 and CV-1 DNA replication, adenovirus type 2 (Ad-2) DNA replication in isolated nuclei was inhibited by d2TTP to the same extent as gamma-polymerase. Ad-2 DNA replication was also inhibited by aphidicolin to the same extent as alpha-polymerase. Synthesis of CV-1 DNA, SV40 DNA, and HSV-1 DNA in intact CV-1 cells was inhibited by aphidicolin. Ad-2 DNA replication was also inhibited, but only at a 100-fold higher concentration. We found no effect of 2'-3'-dideoxythymidine (d2Thd) on cellular or viral DNA replication in spite of the fact that Ad-2 DNA replication in isolated nuclei was inhibited 50% by a ratio of d2TTP/dTTP of 0.02. This was due to the inability of CV-1 and Hela cells to phosphorylate d2Thd to d2TTP. These data are consistent with the hypothesis that DNA polymerase alpha is the only DNA polymerase involved in replicating SV40 DNA and CV-1 DNA and that Ad-2 DNA replication involves both DNA polymerases gamma and alpha.", "contents": "Involvement of eucaryotic deoxyribonucleic acid polymerases alpha and gamma in the replication of cellular and viral deoxyribonucleic acid. In an effort to identify the deoxyribonucleic acid (DNA) polymerase activities responsible for mammalian viral and cellular DNA replication, the effect of DNA synthesis inhibitors on isolated DNA polymerases was compared with their effects on viral and cellular DNA replication in vitro. DNA polymerase alpha, simian virus 40 (SV40) DNA replication in nuclear extracts, and CV-1 cell (the host for SV40) DNA replication in isolated nuclei all responded to DNA synthesis inhibitors in a quantitatively similar manner: they were relatively insensitive to 2',3'-dideoxythymidine 5'-triphosphate (d2TTP), but completely inhibited by aphidicolin, 1-beta-D-arabinofuranosylcytosine 5'-triphosphate (araCTP), and N-ethylmaleimide. In comparison, DNA polymerases beta and gamma were inhibited by d2TTP but insensitive to aphidicolin and 20--30 times less sensitive to araCTP than DNA polymerase alpha. Herpes simplex virus type 1 (HSV-1) DNA polymerase and DNA polymerase alpha were the only enzymes tested that were relatively insensitive to d2TTP; DNA polymerases beta and gamma, phage T4 and T7 DNA polymerases, and Escherichia coli DNA polymerase I were 100--250 times more sensitive. The results with d2TTP were independent of enzyme concentration, primer-template concentration, primer-template choice, and the labeled dNTP. A specific requirement for DNA polymerase alpha in the replication of SV40 DNA was demonstrated by the fact that DNA polymerase alpha was required, in addition to other cytosol proteins, to reconstitute SV40 DNA replication activity in N-ethylmaleimide-inactivated nuclear extracts containing replicating SV40 chromosomes. DNA polymerases beta and gamma did not substitute for DNA polymerase alpha. In contrast to  SV40 and CV-1 DNA replication, adenovirus type 2 (Ad-2) DNA replication in isolated nuclei was inhibited by d2TTP to the same extent as gamma-polymerase. Ad-2 DNA replication was also inhibited by aphidicolin to the same extent as alpha-polymerase. Synthesis of CV-1 DNA, SV40 DNA, and HSV-1 DNA in intact CV-1 cells was inhibited by aphidicolin. Ad-2 DNA replication was also inhibited, but only at a 100-fold higher concentration. We found no effect of 2'-3'-dideoxythymidine (d2Thd) on cellular or viral DNA replication in spite of the fact that Ad-2 DNA replication in isolated nuclei was inhibited 50% by a ratio of d2TTP/dTTP of 0.02. This was due to the inability of CV-1 and Hela cells to phosphorylate d2Thd to d2TTP. These data are consistent with the hypothesis that DNA polymerase alpha is the only DNA polymerase involved in replicating SV40 DNA and CV-1 DNA and that Ad-2 DNA replication involves both DNA polymerases gamma and alpha."}
{"id": "PMID:226128", "title": "Kinetic factors limiting the synthesis of ATP by chromatophores exposed to short flash excitation.", "content": "ATP synthesis was measured after chromatophores from Rhodopseudomonas capsulata had been subjected to illumination by single turnover flashes fired at variable frequencies. Three processes were examined, which under different conditions can limit the net yield of ATP. (1) A process with an apparent relaxation time of 10-20 ms. This reaction probably limits the rate of ATP synthesis in continuous illumination. It has similar time dependence to the stimulation of the carotenoid shift decay by ADP after a single flash. (2) An active state of the ATPase only persists when the chromatophores are excited more often than once in 10 s. This state decays with similar kinetics to the entire carotenoid shift decay. Full activation is achieved after two flashes. (1) and (2) are not significantly affected by concentrations of antimycin A sufficient to block electron flow through the cytochrome b/c2 oxidoreductase and abolish phase III in the generation of the carotenoid shift. (3) In the presence of antimycin A, after the third, fourth and subsequent flashes ATP synthesis is limited by the quantity of reducing equivalents transported through the reaction centre rather than by the level of the electrochemical proton gradient.", "contents": "Kinetic factors limiting the synthesis of ATP by chromatophores exposed to short flash excitation. ATP synthesis was measured after chromatophores from Rhodopseudomonas capsulata had been subjected to illumination by single turnover flashes fired at variable frequencies. Three processes were examined, which under different conditions can limit the net yield of ATP. (1) A process with an apparent relaxation time of 10-20 ms. This reaction probably limits the rate of ATP synthesis in continuous illumination. It has similar time dependence to the stimulation of the carotenoid shift decay by ADP after a single flash. (2) An active state of the ATPase only persists when the chromatophores are excited more often than once in 10 s. This state decays with similar kinetics to the entire carotenoid shift decay. Full activation is achieved after two flashes. (1) and (2) are not significantly affected by concentrations of antimycin A sufficient to block electron flow through the cytochrome b/c2 oxidoreductase and abolish phase III in the generation of the carotenoid shift. (3) In the presence of antimycin A, after the third, fourth and subsequent flashes ATP synthesis is limited by the quantity of reducing equivalents transported through the reaction centre rather than by the level of the electrochemical proton gradient."}
{"id": "PMID:226129", "title": "The orientation of the primary donor in bacterial photosynthesis.", "content": "The triplet state EPR spectra of magnetically aligned whole cells of Rhodopseudomonas viridis and Rhodopseudomonas palustris display a marked dependence on the orientation of the static EPR field with respect to the alignment field direction. This observation implies that the primary donor species on which the triplets are localized are ordered within the membranes. We have developed a theoretical model for the system to enable calculation of the orientation of the magnetic axes of the primary donor species with respect to the membranes in which they reside. The triplet state spectra are generated by an ensemble of partially ordered magnetic systems and a computer simulation of the experimental results. The triplet orientation is very similar for the two organisms studied, where one axis lies predominantly in the plane of the membrane and the other two axes have approximately equal projections onto the normal to the membrane.", "contents": "The orientation of the primary donor in bacterial photosynthesis. The triplet state EPR spectra of magnetically aligned whole cells of Rhodopseudomonas viridis and Rhodopseudomonas palustris display a marked dependence on the orientation of the static EPR field with respect to the alignment field direction. This observation implies that the primary donor species on which the triplets are localized are ordered within the membranes. We have developed a theoretical model for the system to enable calculation of the orientation of the magnetic axes of the primary donor species with respect to the membranes in which they reside. The triplet state spectra are generated by an ensemble of partially ordered magnetic systems and a computer simulation of the experimental results. The triplet orientation is very similar for the two organisms studied, where one axis lies predominantly in the plane of the membrane and the other two axes have approximately equal projections onto the normal to the membrane."}
{"id": "PMID:226130", "title": "Magnetophotoselection of the triplet state of reaction centers from Rhodopseudomonas sphaeroides R-26.", "content": "Reaction centers of the photosynthetic bacterium Rhodopseudomonas sphaeroides R-26, give rise to large triplet state EPR signals upon illumination at low temperature (11 K). Utilizing monochromatic polarized light to generate the EPR spectra (magnetophotoselection) we have shown that the intensities of the observed triplet signals are strongly dependent upon the wavelength and polarization direction of the excitation. These data can be used to calculate the orientations of the excited transition moments with respect to each other and with respect to the triplet state principal magnetic axes system. Our quantitative approach is to follow the procedure outlined in a previous publication (Frank, H.A., Friesner, R., Nairn, J.A., Dismukes, G.C. and Sauer, K. (1979) Biochim. Biophys. Acta 547, 484-501) where computer simulations of the observed triplet state spectra were employed. The results presented in the present work indicate that the transition moment at 870 nm which is associated with the bacteriochlorophyll 'special pair' lies almost entirely along one of the principal magnetic axes of the triplet state. Aso, the 870 nm transition moment makes an angle of approx. 60 degrees with the 546 nm transition moment which is associated with a bacteriopheophytin. This latter result is in agreement with previous photoselection studies on the same bacterial species (Vermeglio, A., Breton, J., Paillotin, G. and Cogdell, R. (1978) Biochim. Biophys. Acta 501, 514-530).", "contents": "Magnetophotoselection of the triplet state of reaction centers from Rhodopseudomonas sphaeroides R-26. Reaction centers of the photosynthetic bacterium Rhodopseudomonas sphaeroides R-26, give rise to large triplet state EPR signals upon illumination at low temperature (11 K). Utilizing monochromatic polarized light to generate the EPR spectra (magnetophotoselection) we have shown that the intensities of the observed triplet signals are strongly dependent upon the wavelength and polarization direction of the excitation. These data can be used to calculate the orientations of the excited transition moments with respect to each other and with respect to the triplet state principal magnetic axes system. Our quantitative approach is to follow the procedure outlined in a previous publication (Frank, H.A., Friesner, R., Nairn, J.A., Dismukes, G.C. and Sauer, K. (1979) Biochim. Biophys. Acta 547, 484-501) where computer simulations of the observed triplet state spectra were employed. The results presented in the present work indicate that the transition moment at 870 nm which is associated with the bacteriochlorophyll 'special pair' lies almost entirely along one of the principal magnetic axes of the triplet state. Aso, the 870 nm transition moment makes an angle of approx. 60 degrees with the 546 nm transition moment which is associated with a bacteriopheophytin. This latter result is in agreement with previous photoselection studies on the same bacterial species (Vermeglio, A., Breton, J., Paillotin, G. and Cogdell, R. (1978) Biochim. Biophys. Acta 501, 514-530)."}
{"id": "PMID:226131", "title": "Exchange integral for a variety of tetranuclear ferredoxins.", "content": "The temperature dependence of EPR spectra of oxidized [4Fe-4S](-1,-2) ferredoxins (previously designated HiPIP) and a reduced [4Fe-4S](-2,-3) ferredoxin have been analyzed so as to determine the energy of a low-lying excited electronic state. The values obtained were: Center S-3 from beef heart, 44 cm-1; Center S-3 from mung bean, 53 cm-1; the [4Fe-4S](-1,-2) ferredoxin from Thermus thermophilus, 78 cm-1; Center N-2 of NADH ubiquinone reductase, 83 cm-1. Increasing axial distortion in the EPR spectra of the [4Fe-4S](-1,-2), ferrodoxins was associated with higher energy differences. Center N-2, a [Fe-4S](-2,-3) iron-sulfur cluster does not fit this relationship.", "contents": "Exchange integral for a variety of tetranuclear ferredoxins. The temperature dependence of EPR spectra of oxidized [4Fe-4S](-1,-2) ferredoxins (previously designated HiPIP) and a reduced [4Fe-4S](-2,-3) ferredoxin have been analyzed so as to determine the energy of a low-lying excited electronic state. The values obtained were: Center S-3 from beef heart, 44 cm-1; Center S-3 from mung bean, 53 cm-1; the [4Fe-4S](-1,-2) ferredoxin from Thermus thermophilus, 78 cm-1; Center N-2 of NADH ubiquinone reductase, 83 cm-1. Increasing axial distortion in the EPR spectra of the [4Fe-4S](-1,-2), ferrodoxins was associated with higher energy differences. Center N-2, a [Fe-4S](-2,-3) iron-sulfur cluster does not fit this relationship."}
{"id": "PMID:226132", "title": "Characterization of iron-sulphur centres of plant mitochondria by microwave power saturation.", "content": "The electron spin relaxation of iron-sulphur centres and ubisemiquinones of plant mitochondria was studied by microwave power saturation of the respective EPR signals. In the microwave power saturation technique, the experimental saturation data were fitted by a least-squares procedure to a saturation function which is characterized by the power for half-saturation (P1/2) and the inhomogeneity parameter (b). Since the theoretical saturation curves were based on a one-electron spin system, it became possible to differentiate between EPR signals of iron-sulphur centres which have similar g values but different P1/2 values. If the difference in the P1/2 values of the overlapped components was small, no significant deviation from these theoretical saturation curves was observed, as shown for the overlapped signals of centre S-3 and the Ruzicka centre of mung bean mitochondria. By contrast, the microwave power saturation data for the g = 1.93 signal (17--26 K) of Arum maculatum submitochondrial particles reduced by succinate could not be fitted using one-electron saturation curves. Reduction by NADH resulted in a stronger deviation. Since the iron-sulphur centres of Complex I were present only in an unusually low concentration in A. maculatum mitochondria, it was proposed that an iron-sulphur centre of the external NADH dehydrogenase contributes to the spectrum of centre S-1. For mung bean mitochondria, the g = 1.93 signal below 20 K could be attributed mainly to centre N-2. The microwave power saturation technique was also suitable for detecting magnetic interactions between paramagnetic centres. From the saturation data of the complex spectrum attributable to centre S-3 and an interacting ubisemiquinone pair in mung bean mitochondria (oxidized state) followed that centre S-3 has a faster electron spin relaxation than the ubisemiquinone molecules. It is noteworthy that the differences in the relaxation rates were maintained despite the interaction between centre S-3 and the ubisemiquinones. Furthermore, a relaxation enhancement was observed for centre S-1 of A. maculatum submitochondrial particles upon reduction of centre S-2 by dithionite. This indicated a magnetic interaction between centres S-1 and S-2.", "contents": "Characterization of iron-sulphur centres of plant mitochondria by microwave power saturation. The electron spin relaxation of iron-sulphur centres and ubisemiquinones of plant mitochondria was studied by microwave power saturation of the respective EPR signals. In the microwave power saturation technique, the experimental saturation data were fitted by a least-squares procedure to a saturation function which is characterized by the power for half-saturation (P1/2) and the inhomogeneity parameter (b). Since the theoretical saturation curves were based on a one-electron spin system, it became possible to differentiate between EPR signals of iron-sulphur centres which have similar g values but different P1/2 values. If the difference in the P1/2 values of the overlapped components was small, no significant deviation from these theoretical saturation curves was observed, as shown for the overlapped signals of centre S-3 and the Ruzicka centre of mung bean mitochondria. By contrast, the microwave power saturation data for the g = 1.93 signal (17--26 K) of Arum maculatum submitochondrial particles reduced by succinate could not be fitted using one-electron saturation curves. Reduction by NADH resulted in a stronger deviation. Since the iron-sulphur centres of Complex I were present only in an unusually low concentration in A. maculatum mitochondria, it was proposed that an iron-sulphur centre of the external NADH dehydrogenase contributes to the spectrum of centre S-1. For mung bean mitochondria, the g = 1.93 signal below 20 K could be attributed mainly to centre N-2. The microwave power saturation technique was also suitable for detecting magnetic interactions between paramagnetic centres. From the saturation data of the complex spectrum attributable to centre S-3 and an interacting ubisemiquinone pair in mung bean mitochondria (oxidized state) followed that centre S-3 has a faster electron spin relaxation than the ubisemiquinone molecules. It is noteworthy that the differences in the relaxation rates were maintained despite the interaction between centre S-3 and the ubisemiquinones. Furthermore, a relaxation enhancement was observed for centre S-1 of A. maculatum submitochondrial particles upon reduction of centre S-2 by dithionite. This indicated a magnetic interaction between centres S-1 and S-2."}
{"id": "PMID:226133", "title": "Intramolecular electron transfer and binding constants in iron hexacyanide-cytochrome c complexes as studied by pulse radiolysis.", "content": "Internal oxidation and reduction rates of horse cytochrome c in the complexes CII . Fe(III)(CN)6(3)- and CIII . Fe(II)(CN)6(4)-, are 4.6 . 10(4)s-1 and 3.3 . 10(2)s-1, respectively. The binding site of the iron hexacyanide ions on either CII or CIII are kinetically almost indistinguishable; binding constants range from 0.87 . 10(3) to 2 . 10(3)M-1. The present pulse radiolytic kinetic data is compared with that from NMR, T-jump and equilibrium dialysis studies.", "contents": "Intramolecular electron transfer and binding constants in iron hexacyanide-cytochrome c complexes as studied by pulse radiolysis. Internal oxidation and reduction rates of horse cytochrome c in the complexes CII . Fe(III)(CN)6(3)- and CIII . Fe(II)(CN)6(4)-, are 4.6 . 10(4)s-1 and 3.3 . 10(2)s-1, respectively. The binding site of the iron hexacyanide ions on either CII or CIII are kinetically almost indistinguishable; binding constants range from 0.87 . 10(3) to 2 . 10(3)M-1. The present pulse radiolytic kinetic data is compared with that from NMR, T-jump and equilibrium dialysis studies."}
{"id": "PMID:226134", "title": "The ATPase inhibitor protein in oxidative phosphorylation. The rate-limiting factor to phosphorylation in submitochondrial particles.", "content": "1. Purified luciferase and luciferin were used to study the time course of phosphorylation in submitochondrial particles. The light emitted was detected by a single-photon counter, using a multichannel analyser, and the results were analysed by an 'on-line' digital computer. 2. Using NADH as substrate, phosphorylation showed, in general, four phases. These were (i) a period of increasing rate ('lag'); (ii) a period of constant (positive) rate; (iii) a period of zero net rate (plateau), when the phosphorylation potential was maintained at its equilibrium value, and (iv) a period of negative rate (atp hydrolysis) after all the oxygen has been consumed. 3. The lag phase, several seconds in length, was a function of the inhibitor protein content of the particles. It was decreased in particles treated to remove the inhibitor protein, either by prior energisation of the particles with NADH, or by addition of aurovertin, which competes with the inhibitor protein for the ATPase. It was concluded that the ATPase inhibitor inhibits both ATP synthesis and hydrolysis by the ATPase. 4. The rate constant for the release of the inhibitor protein from the energised membrane was determined from the time course of ATP production during the lag phase. The activation energy of this process was measured from the temperature dependence of the lag, and was shown to be 13.3 kcal/mol, lower than the activation energy of ATP synthesis or NADH oxidation. 5. The rate constant for inhibitor release was dependent on 'energisation' of the membrane, being lower in the presence of uncouplers. However, it was possible to decrease the rate constant considerably with agents that collapsed the membrane potential without uncoupling the membrane. It was concluded that the inhibitor protein responded to the membrane potential component of the energisation. 6. A kinetic model for energy-dependent dissociation of the ATPase-inhibitor complex is proposed.", "contents": "The ATPase inhibitor protein in oxidative phosphorylation. The rate-limiting factor to phosphorylation in submitochondrial particles. 1. Purified luciferase and luciferin were used to study the time course of phosphorylation in submitochondrial particles. The light emitted was detected by a single-photon counter, using a multichannel analyser, and the results were analysed by an 'on-line' digital computer. 2. Using NADH as substrate, phosphorylation showed, in general, four phases. These were (i) a period of increasing rate ('lag'); (ii) a period of constant (positive) rate; (iii) a period of zero net rate (plateau), when the phosphorylation potential was maintained at its equilibrium value, and (iv) a period of negative rate (atp hydrolysis) after all the oxygen has been consumed. 3. The lag phase, several seconds in length, was a function of the inhibitor protein content of the particles. It was decreased in particles treated to remove the inhibitor protein, either by prior energisation of the particles with NADH, or by addition of aurovertin, which competes with the inhibitor protein for the ATPase. It was concluded that the ATPase inhibitor inhibits both ATP synthesis and hydrolysis by the ATPase. 4. The rate constant for the release of the inhibitor protein from the energised membrane was determined from the time course of ATP production during the lag phase. The activation energy of this process was measured from the temperature dependence of the lag, and was shown to be 13.3 kcal/mol, lower than the activation energy of ATP synthesis or NADH oxidation. 5. The rate constant for inhibitor release was dependent on 'energisation' of the membrane, being lower in the presence of uncouplers. However, it was possible to decrease the rate constant considerably with agents that collapsed the membrane potential without uncoupling the membrane. It was concluded that the inhibitor protein responded to the membrane potential component of the energisation. 6. A kinetic model for energy-dependent dissociation of the ATPase-inhibitor complex is proposed."}
{"id": "PMID:226135", "title": "Purification and properties of cytochrome c-553, an electron acceptor for formate dehydrogenase of Desulfovibrio vulgaris, Miyazaki.", "content": "Cytochrome c-553 of Desulfovibrio vulgaris, Miyazaki, was purified to homogeneity. The absorption spectrum of the ferro form has four peaks at 553, 525, 417 and 317 nm with a plateau near 280 nm, and that of the ferri form has three peaks at 525, 410 and 360 nm with a plateau near 280 nm and a shoulder at 560 nm. The millimolar absorbance coefficient of the alpha-peak of the ferro form is 23.9. The molecular weight of cytochrome c-553 is 8000, and it contains one heme. Its isoelectric point is rather alkaline, and its standard redox potential is -0.26 V at pH 7.0. Its amino acid composition is unique; it lacks proline, isoleucine and tryptophan. Ferrocytochrome c-553 does not combine with CO, nor does it transfer electrons directly to various redox carriers such as flavin nucleotides, methylene blue, indigodisulfonate, 5-methylphenazinium methyl sulfate, 1-methoxy-5-methylphenazinium methyl sulfate, viologens and cytochrome c3, but is oxidized by ferricyanide or by O2. Cytochrome c-553 can be reduced by formate dehydrogenase of this bacterium in the presence of formate, but not by hydrogenase under H2. The formate dehydrogenase does not reduce cytochrome c3 in the presence of formate. The systematic name for formate dehydrogenase of D. vulgaris is, therefore, established as formate:ferricytochrome c-553 oxidoreductase in EC subclass 1.22.-.", "contents": "Purification and properties of cytochrome c-553, an electron acceptor for formate dehydrogenase of Desulfovibrio vulgaris, Miyazaki. Cytochrome c-553 of Desulfovibrio vulgaris, Miyazaki, was purified to homogeneity. The absorption spectrum of the ferro form has four peaks at 553, 525, 417 and 317 nm with a plateau near 280 nm, and that of the ferri form has three peaks at 525, 410 and 360 nm with a plateau near 280 nm and a shoulder at 560 nm. The millimolar absorbance coefficient of the alpha-peak of the ferro form is 23.9. The molecular weight of cytochrome c-553 is 8000, and it contains one heme. Its isoelectric point is rather alkaline, and its standard redox potential is -0.26 V at pH 7.0. Its amino acid composition is unique; it lacks proline, isoleucine and tryptophan. Ferrocytochrome c-553 does not combine with CO, nor does it transfer electrons directly to various redox carriers such as flavin nucleotides, methylene blue, indigodisulfonate, 5-methylphenazinium methyl sulfate, 1-methoxy-5-methylphenazinium methyl sulfate, viologens and cytochrome c3, but is oxidized by ferricyanide or by O2. Cytochrome c-553 can be reduced by formate dehydrogenase of this bacterium in the presence of formate, but not by hydrogenase under H2. The formate dehydrogenase does not reduce cytochrome c3 in the presence of formate. The systematic name for formate dehydrogenase of D. vulgaris is, therefore, established as formate:ferricytochrome c-553 oxidoreductase in EC subclass 1.22.-."}
{"id": "PMID:226136", "title": "Membrane lipid fluidity and its effect on the activation energy of membrane-associated enzymes.", "content": "1. The fatty acid composition of mitochondrial membranes from sheep and rats was altered by feeding these animals diets which were rich in unsaturated fatty acids. Changes in membrane lipid fluidity resulting from the altered membrane lipid composition were assessed by determining the upper temperature limit of the disorder-order transition (Tf) and the Arrhenius activation energy (Ea) of succinate oxidase. 2. After feeding the unsaturated fatty acid-rich diet to sheep the Ea, in the temperature range above Tf, increased from 8 to 63 kJ . mol-1 while Tf decreased from 32 to 15 degrees C. Rats fed an unsaturated fatty acid-rich diet exhibited an increase in Ea from 17 to 63 kJ . mol-1 and a decrease in Tf from 23 to 4 degrees C. 3. This decrease in Tf was related to an increase in the ratio of linoleic acid to stearic acid in the membrane lipid. Tf was not related to the proportion of unsaturated fatty acids in the membrane lipids, although an increase in unsaturation usually led to a decrease in Tf. 4. The results show that membrane lipid fluidity has a direct influence on the conformation of the active site of some membrane-associated enzymes, with the result that such enzymes display a higher Ea when the membrane lipids are comparatively more fluid. The increase in Ea of membrane-associated enzymes which accompanies changes in the physical state of membrane suggests that some proteins may phase separate with the more fluid lipids at low temperatures.", "contents": "Membrane lipid fluidity and its effect on the activation energy of membrane-associated enzymes. 1. The fatty acid composition of mitochondrial membranes from sheep and rats was altered by feeding these animals diets which were rich in unsaturated fatty acids. Changes in membrane lipid fluidity resulting from the altered membrane lipid composition were assessed by determining the upper temperature limit of the disorder-order transition (Tf) and the Arrhenius activation energy (Ea) of succinate oxidase. 2. After feeding the unsaturated fatty acid-rich diet to sheep the Ea, in the temperature range above Tf, increased from 8 to 63 kJ . mol-1 while Tf decreased from 32 to 15 degrees C. Rats fed an unsaturated fatty acid-rich diet exhibited an increase in Ea from 17 to 63 kJ . mol-1 and a decrease in Tf from 23 to 4 degrees C. 3. This decrease in Tf was related to an increase in the ratio of linoleic acid to stearic acid in the membrane lipid. Tf was not related to the proportion of unsaturated fatty acids in the membrane lipids, although an increase in unsaturation usually led to a decrease in Tf. 4. The results show that membrane lipid fluidity has a direct influence on the conformation of the active site of some membrane-associated enzymes, with the result that such enzymes display a higher Ea when the membrane lipids are comparatively more fluid. The increase in Ea of membrane-associated enzymes which accompanies changes in the physical state of membrane suggests that some proteins may phase separate with the more fluid lipids at low temperatures."}
{"id": "PMID:226137", "title": "A study of the incorporation of cytochrome oxidase into planar synthetic membranes.", "content": "Cytochrome oxidase molecules were incorporated into black lipid membranes and into a new form of planar synthetic membrane. Studies of these membranes indicated that the incorporation of large membrane bound enzymes into black lipid membranes involves difficulties fundamental to this technique. On the other hand the new method described in this paper is more promising.", "contents": "A study of the incorporation of cytochrome oxidase into planar synthetic membranes. Cytochrome oxidase molecules were incorporated into black lipid membranes and into a new form of planar synthetic membrane. Studies of these membranes indicated that the incorporation of large membrane bound enzymes into black lipid membranes involves difficulties fundamental to this technique. On the other hand the new method described in this paper is more promising."}
{"id": "PMID:226139", "title": "Golgi fractions from livers of control and ethanol-intoxicated rats. Enzymic and morphologic properties following rapid isolation.", "content": "Following rapid isolation, it has been found that Golgi apparatus from ethanol-intoxicated animals contain high levels of galactosyltransferase but also detectable glucose-6-phosphatase and microsomal esterase, as well as 5'-nucleotidase activity. In experiments carried out in parallel on littermate animals but without intoxication, similar recoveries and specific activities of the four enzymes were observed. Morphologic analysis of Golgi fractions isolated from control animals demonstrated no striking morphologic difference to those from the ethanol-intoxicated animals. Indeed, using galloyl glucose-lead staining techniques to mark the lipoprotein particles in situ, it was found that all Golgi apparatus of hepatocytes from control animals were marked by very low density lipoprotein particles. It is therefore concluded that within the limits of the present analyses, Golgi fractions isolated from control animals are as valid as those isolated from ethanol-intoxicated rats.", "contents": "Golgi fractions from livers of control and ethanol-intoxicated rats. Enzymic and morphologic properties following rapid isolation. Following rapid isolation, it has been found that Golgi apparatus from ethanol-intoxicated animals contain high levels of galactosyltransferase but also detectable glucose-6-phosphatase and microsomal esterase, as well as 5'-nucleotidase activity. In experiments carried out in parallel on littermate animals but without intoxication, similar recoveries and specific activities of the four enzymes were observed. Morphologic analysis of Golgi fractions isolated from control animals demonstrated no striking morphologic difference to those from the ethanol-intoxicated animals. Indeed, using galloyl glucose-lead staining techniques to mark the lipoprotein particles in situ, it was found that all Golgi apparatus of hepatocytes from control animals were marked by very low density lipoprotein particles. It is therefore concluded that within the limits of the present analyses, Golgi fractions isolated from control animals are as valid as those isolated from ethanol-intoxicated rats."}
{"id": "PMID:226140", "title": "Interaction of plasma apolipoproteins with lipid monolayers.", "content": "The monolayer technique has been used to study the interaction of lipids with plasma apolipoproteins. Apolipoprotein C-II and C-III from human very low density lipoproteins, apolipoprotein A-I from human high density lipoproteins and arginine-rich protein from swine very low density lipoproteins were studied. The injection of each apoprotein underneath a monolayer of egg phosphatidy[14C]choline at 20 mN/m caused an increase in surface pressure to approximately 30 mN/m. With apolipoprotein C-II and apolipoprotein C-III there was a decrease in surface radioactivity indicating that the apoproteins were removing phospholipid from the interface; the removal of phospholipid was specific for apolipoprotein C-II and apolipoprotein C-III. Although there was a removal of phospholipid from the monolayer, the surface pressure remained constant and was due to the accumulation of apoprotein at the interface. The rate of surface radioactivity decrease was a function of protein concentration, required lipid in a fluid state and, of the lipids tested, was specific for phosphatidylcholine. Cholesterol and phosphatidylinositol were not removed from the interface. The addition of 33 mol% cholesterol to the phosphatidylcholine monolayer did not affect the removal of phospholipids by apolipoprotein C-III. The addition of phospholipid liposomes to the subphase greatly facilitated the apolipoprotein C-II-mediated removal of phospholipid from the interface. Although apolipoprotein A-I and arginine-rich protein gave surface pressure increases, phospholipid was only slightly removed fromthe interface by the addition of liposomes. Based on these findings, we conclude that the apolipoproteins C interact specifically with phosphatidylcholine at the interface. This interaction is important as it relates to the transfer of the apolipoproteins C and phospholipids from very low density lipoproteins to other plasma lipoproteins. The addition of human plasma high density lipoproteins or very low density lipoproteins to the subphase increased the apolipoprotein C-mediated removal of phosphatidyl[14C]choline from the interface 3--4 fold. Low density lipoproteins did not affect the rate of decrease. During lipolysis of very low density lipoproteins to the subphase increased the apolipoprotein C-mediated removal of with the lipid monolayer. Lipolysis experiments were performed in a monolayer trough containing a surface film of egg phosphatidyl[14C]choline and a subphase of very low density lipoproteins and bovine serum albumin. Lipolysis was initiated by the addition of purified milk lipoprotein lipase to the subphase. As a result of lipolysis, there was a decrease in surface radioactivity of phosphatidylcholine. The pre-addition of high density lipoproteins decreased the rate of decrease in surface radioactivity...", "contents": "Interaction of plasma apolipoproteins with lipid monolayers. The monolayer technique has been used to study the interaction of lipids with plasma apolipoproteins. Apolipoprotein C-II and C-III from human very low density lipoproteins, apolipoprotein A-I from human high density lipoproteins and arginine-rich protein from swine very low density lipoproteins were studied. The injection of each apoprotein underneath a monolayer of egg phosphatidy[14C]choline at 20 mN/m caused an increase in surface pressure to approximately 30 mN/m. With apolipoprotein C-II and apolipoprotein C-III there was a decrease in surface radioactivity indicating that the apoproteins were removing phospholipid from the interface; the removal of phospholipid was specific for apolipoprotein C-II and apolipoprotein C-III. Although there was a removal of phospholipid from the monolayer, the surface pressure remained constant and was due to the accumulation of apoprotein at the interface. The rate of surface radioactivity decrease was a function of protein concentration, required lipid in a fluid state and, of the lipids tested, was specific for phosphatidylcholine. Cholesterol and phosphatidylinositol were not removed from the interface. The addition of 33 mol% cholesterol to the phosphatidylcholine monolayer did not affect the removal of phospholipids by apolipoprotein C-III. The addition of phospholipid liposomes to the subphase greatly facilitated the apolipoprotein C-II-mediated removal of phospholipid from the interface. Although apolipoprotein A-I and arginine-rich protein gave surface pressure increases, phospholipid was only slightly removed fromthe interface by the addition of liposomes. Based on these findings, we conclude that the apolipoproteins C interact specifically with phosphatidylcholine at the interface. This interaction is important as it relates to the transfer of the apolipoproteins C and phospholipids from very low density lipoproteins to other plasma lipoproteins. The addition of human plasma high density lipoproteins or very low density lipoproteins to the subphase increased the apolipoprotein C-mediated removal of phosphatidyl[14C]choline from the interface 3--4 fold. Low density lipoproteins did not affect the rate of decrease. During lipolysis of very low density lipoproteins to the subphase increased the apolipoprotein C-mediated removal of with the lipid monolayer. Lipolysis experiments were performed in a monolayer trough containing a surface film of egg phosphatidyl[14C]choline and a subphase of very low density lipoproteins and bovine serum albumin. Lipolysis was initiated by the addition of purified milk lipoprotein lipase to the subphase. As a result of lipolysis, there was a decrease in surface radioactivity of phosphatidylcholine. The pre-addition of high density lipoproteins decreased the rate of decrease in surface radioactivity..."}
{"id": "PMID:226141", "title": "Differences in membrane unsaturated fatty acids and electron spin resonance in different types of myeloid leukemia cells.", "content": "The fatty acid composition and some physical properties of intact cells and isolated plasma membranes of two types of mouse myeloid leukemia cell clone grown in culture have been examined. One clone type, MGI+D+, can be induced by the macrophage and granulocyte-inducing protein (MGI) to differentiate into mature macrophages and granulocytes. The other clone type, MGI+D-, could not be induced to differentiate into mature cells. A two-fold increase in the ratio of saturated fatty acid to unsaturated fatty acid was found in the MGI+D- compared to the MGI+D+ clones. The MGI+D- clones produced an unusual polyunsaturated C20:5 fatty acid at 28 degrees C, whereas the MGI+D+ clones did not grow at this temperature. The cells and their isolated plasma membranes were studied by electron spin resonance. The motion of the 5-nitroxide stearate spin label was found to be higher in the intact cells and in the membranes of MGI+D- clones than of the MGI+D+ clones. The cells of MGI+D+ clones showed a similar freedom of motion to normal myeloblasts from the bone marrow. The results indicate that myeloid leukemia cells which differ in their competence to be induced to differentiate into mature cells have different physical properties of their plasma membranes and that this is correlated with their fatty acid acyl chain composition.", "contents": "Differences in membrane unsaturated fatty acids and electron spin resonance in different types of myeloid leukemia cells. The fatty acid composition and some physical properties of intact cells and isolated plasma membranes of two types of mouse myeloid leukemia cell clone grown in culture have been examined. One clone type, MGI+D+, can be induced by the macrophage and granulocyte-inducing protein (MGI) to differentiate into mature macrophages and granulocytes. The other clone type, MGI+D-, could not be induced to differentiate into mature cells. A two-fold increase in the ratio of saturated fatty acid to unsaturated fatty acid was found in the MGI+D- compared to the MGI+D+ clones. The MGI+D- clones produced an unusual polyunsaturated C20:5 fatty acid at 28 degrees C, whereas the MGI+D+ clones did not grow at this temperature. The cells and their isolated plasma membranes were studied by electron spin resonance. The motion of the 5-nitroxide stearate spin label was found to be higher in the intact cells and in the membranes of MGI+D- clones than of the MGI+D+ clones. The cells of MGI+D+ clones showed a similar freedom of motion to normal myeloblasts from the bone marrow. The results indicate that myeloid leukemia cells which differ in their competence to be induced to differentiate into mature cells have different physical properties of their plasma membranes and that this is correlated with their fatty acid acyl chain composition."}
{"id": "PMID:226142", "title": "Pressure effects on lipid-protein interactions in (NA+ + K+)-ATPase.", "content": "The (Na+ + K+)-stimulated ATPase activity decreases with increasing pressure and a plot of the logarithm of the activity versus pressure shows a change in slope at a defined breakpoint pressure (Pb). The value of Pb increases linearly with increasing temperature. A dT/dP value of 27.7 +- 0.4 (S.D.) K/1000 atm is obtained. This is in very good agreement with the pressure shift for the melting transitions in phospholipids and aliphatic chains. This strongly indicates that an aliphatic chain melting process is involved in the breakpoint in the Arrhenius plot and pressure dependence of (Na+ + K+)-ATPase. The p-nitrophenyl phosphatase activity of this enzyme also decreases with pressure. In this case the plot of the logarithm of the activity versus pressure is linear without a break-point. The temperature dependence for (Na+ + K+)-ATPase was also studied in the presence of fluidizing drugs: desipramine and benzylalcohol. The presence of these drugs had no effect on the inflection point in the Arrhenius plot.", "contents": "Pressure effects on lipid-protein interactions in (NA+ + K+)-ATPase. The (Na+ + K+)-stimulated ATPase activity decreases with increasing pressure and a plot of the logarithm of the activity versus pressure shows a change in slope at a defined breakpoint pressure (Pb). The value of Pb increases linearly with increasing temperature. A dT/dP value of 27.7 +- 0.4 (S.D.) K/1000 atm is obtained. This is in very good agreement with the pressure shift for the melting transitions in phospholipids and aliphatic chains. This strongly indicates that an aliphatic chain melting process is involved in the breakpoint in the Arrhenius plot and pressure dependence of (Na+ + K+)-ATPase. The p-nitrophenyl phosphatase activity of this enzyme also decreases with pressure. In this case the plot of the logarithm of the activity versus pressure is linear without a break-point. The temperature dependence for (Na+ + K+)-ATPase was also studied in the presence of fluidizing drugs: desipramine and benzylalcohol. The presence of these drugs had no effect on the inflection point in the Arrhenius plot."}
{"id": "PMID:226143", "title": "Localization and characterization of transport-related elements in the plasma membrane of turtle bladder epithelial cells.", "content": "A mixed membrane preparation obtained from turtle bladder epithelial cells contains (Na+ + K+)-ATPase, adenylate cyclase and protein kinase, which interact with ouabain, norepinephrine and cyclic AMP, respectively. When such a preparation is obtained from bladders which had been preexposed to serosal fluids containing the tritiated form of 4,4'-diisothiocyano-2,2'-disulfonic stilbene, the subsequently isolated membrane proteins are enriched in tritium as well as in the afore-mentioned enzymes, none of which is inhibited. Free-flow electrophoresis separates the mixed membrane preparation into two distinguishable groups: one, construed as apical membranes, is enriched in norepinephrine-sensitive adenylate cyclase and cyclic AMP-sensitive protein kinase; the other, construed as basal-lateral membranes, is enriched in ouabain-sensitive ATPase and 4,4'-diisothiocyano-2,2'-disulfonic stilbene-binding proteins. The physiological counterparts of these enzymatically defined membrane markers are the mucosal sidedness of the transport effects of norepinephrine and cyclic AMP derivatives and the serosal sidedness of the transport effects of ouabain and disulfonic stilbenes in the intact turtle bladder. The discreteness and ion selectivity of each membrane-bound, transport-related element are discussed in relation to the corresponding characteristics of each transport process in vivo; the possibility of regulation of anion transport by adenylate cyclase-protein kinase system is also discussed.", "contents": "Localization and characterization of transport-related elements in the plasma membrane of turtle bladder epithelial cells. A mixed membrane preparation obtained from turtle bladder epithelial cells contains (Na+ + K+)-ATPase, adenylate cyclase and protein kinase, which interact with ouabain, norepinephrine and cyclic AMP, respectively. When such a preparation is obtained from bladders which had been preexposed to serosal fluids containing the tritiated form of 4,4'-diisothiocyano-2,2'-disulfonic stilbene, the subsequently isolated membrane proteins are enriched in tritium as well as in the afore-mentioned enzymes, none of which is inhibited. Free-flow electrophoresis separates the mixed membrane preparation into two distinguishable groups: one, construed as apical membranes, is enriched in norepinephrine-sensitive adenylate cyclase and cyclic AMP-sensitive protein kinase; the other, construed as basal-lateral membranes, is enriched in ouabain-sensitive ATPase and 4,4'-diisothiocyano-2,2'-disulfonic stilbene-binding proteins. The physiological counterparts of these enzymatically defined membrane markers are the mucosal sidedness of the transport effects of norepinephrine and cyclic AMP derivatives and the serosal sidedness of the transport effects of ouabain and disulfonic stilbenes in the intact turtle bladder. The discreteness and ion selectivity of each membrane-bound, transport-related element are discussed in relation to the corresponding characteristics of each transport process in vivo; the possibility of regulation of anion transport by adenylate cyclase-protein kinase system is also discussed."}
{"id": "PMID:226144", "title": "Inhibitory effect of methylated derivatives of guanylic acid for protein synthesis with reference to the functional structure of the 5'-'cap' in viral messenger RNA.", "content": "Guanylic acid modified variously with methyl groups on base or sugar moieties were synthesized chemically and their inhibitory effects on protein synthesis were tesetd in a wheat germ cell-free system using mRNAs from cytoplasmic polyhedrosis virus and tobacco mosaic virus. The confronting dinucleotide m7G5' pppA that corresponds to the most simple 'cap' structure of an eukaryotic mRNA is a strong inhibitor of protein synthesis, but non-methylated G5' pppA or G5' ppA is not inhibitory. The strong inhibitory effect is observed only by 7-methylguanylic acid (pm7G). Among 11 derivatives of pG, the most effective inhibitors are methylated at the 7-position. Further methylation at the other position sometimes cancels the inhibitory effect. Although pm7G carries a positively charged base, other nucleotides which carry a plus charged base (1-methyladenylic acid and 2-methylthio-7-methylinosinic acid) were not inhibitory. Thus, methylation at the 7-position on guanylic acid is specifically required for the inhibitory effect. Addition of pm7G was inhibitory for the formation of the initiation complex for eukaryotic protein synthesis. These results suggest that the 'cap' component containing 7-methylguanylic acid in viral mRNA participates during protein synthesis, especially in its initial steps. Protein synthesis in a bacterial cell-free system was not inhibited by addition of m7GpppA or pm7G when either TMV RNA or phage MS2 RNA was used as an mRNA.", "contents": "Inhibitory effect of methylated derivatives of guanylic acid for protein synthesis with reference to the functional structure of the 5'-'cap' in viral messenger RNA. Guanylic acid modified variously with methyl groups on base or sugar moieties were synthesized chemically and their inhibitory effects on protein synthesis were tesetd in a wheat germ cell-free system using mRNAs from cytoplasmic polyhedrosis virus and tobacco mosaic virus. The confronting dinucleotide m7G5' pppA that corresponds to the most simple 'cap' structure of an eukaryotic mRNA is a strong inhibitor of protein synthesis, but non-methylated G5' pppA or G5' ppA is not inhibitory. The strong inhibitory effect is observed only by 7-methylguanylic acid (pm7G). Among 11 derivatives of pG, the most effective inhibitors are methylated at the 7-position. Further methylation at the other position sometimes cancels the inhibitory effect. Although pm7G carries a positively charged base, other nucleotides which carry a plus charged base (1-methyladenylic acid and 2-methylthio-7-methylinosinic acid) were not inhibitory. Thus, methylation at the 7-position on guanylic acid is specifically required for the inhibitory effect. Addition of pm7G was inhibitory for the formation of the initiation complex for eukaryotic protein synthesis. These results suggest that the 'cap' component containing 7-methylguanylic acid in viral mRNA participates during protein synthesis, especially in its initial steps. Protein synthesis in a bacterial cell-free system was not inhibited by addition of m7GpppA or pm7G when either TMV RNA or phage MS2 RNA was used as an mRNA."}
{"id": "PMID:226145", "title": "Phosphorlyation of H1 and H5 histones by cyclic AMP-dependent protein kinase reduces DNA binding.", "content": "Phosphorylation of H1 histones by cyclic AMP-dependent protein kinase may be an important transcriptional control mechanism. We have used affinity chromatography to examine the effect of phosphorylation by this enzyme on the DNA-binding properties of calf thymus H1 histones and two highly basic H1 homologues from condensed and transcriptionally silent nuclei: duck erythrocyte H5 and Strongylocentrotus purpuratus sperm H1. Without in vitro phosphorylation, all three histones were eluted from native DNA-Sephadex G-25 columns at salt concentrations which closely resembled those required to extract these histones from nuclei or chromatin. When a small portion of radioactively phosphorylated histone was chromatographed with untreated carrier histone, the phosphorylated species was consistently eluted from the DNA column at slightly lower salt concentrations than the main histone peak. Rechromatography experiments showed that in vitro phosphorylation of H1 can shift its elution position to lower salt concentrations.", "contents": "Phosphorlyation of H1 and H5 histones by cyclic AMP-dependent protein kinase reduces DNA binding. Phosphorylation of H1 histones by cyclic AMP-dependent protein kinase may be an important transcriptional control mechanism. We have used affinity chromatography to examine the effect of phosphorylation by this enzyme on the DNA-binding properties of calf thymus H1 histones and two highly basic H1 homologues from condensed and transcriptionally silent nuclei: duck erythrocyte H5 and Strongylocentrotus purpuratus sperm H1. Without in vitro phosphorylation, all three histones were eluted from native DNA-Sephadex G-25 columns at salt concentrations which closely resembled those required to extract these histones from nuclei or chromatin. When a small portion of radioactively phosphorylated histone was chromatographed with untreated carrier histone, the phosphorylated species was consistently eluted from the DNA column at slightly lower salt concentrations than the main histone peak. Rechromatography experiments showed that in vitro phosphorylation of H1 can shift its elution position to lower salt concentrations."}
{"id": "PMID:226146", "title": "Isoenzymic forms of NAD-linked glycerol-3-phosphate dehydrogenase from rabbit brain.", "content": "Two major enzyme forms of cytosolic NAD-linked glycerol-3-phosphate dehydrogenase in rabbit brain have been purified to apparent homogeneity. One major enzyme form designated I6.5 exhibits an iso-electric point at pH 6.5, and is indistinguishable from the major form I6.5 found in other tissues. The other major form, designated I5.9, has an isolectric point at pH 5.9, and by amino acid analysis is shown to be a true isoenzyme distinct from form I6.5. Form I5.9 appears to be closely related to or identical with the major enzyme characteristic of heart. Neither the brain enzyme form I5.9 nor the major heart isoenzyme are inhibited by antiserum to the muscle enzyme. Because of the high apparent Km for NADH, it is postulated that the brain isoenzyme I5.9 serves to maintain glycolysis when NADH levels rise under relatively anaerobic conditions especially during fetal and neonatal development.", "contents": "Isoenzymic forms of NAD-linked glycerol-3-phosphate dehydrogenase from rabbit brain. Two major enzyme forms of cytosolic NAD-linked glycerol-3-phosphate dehydrogenase in rabbit brain have been purified to apparent homogeneity. One major enzyme form designated I6.5 exhibits an iso-electric point at pH 6.5, and is indistinguishable from the major form I6.5 found in other tissues. The other major form, designated I5.9, has an isolectric point at pH 5.9, and by amino acid analysis is shown to be a true isoenzyme distinct from form I6.5. Form I5.9 appears to be closely related to or identical with the major enzyme characteristic of heart. Neither the brain enzyme form I5.9 nor the major heart isoenzyme are inhibited by antiserum to the muscle enzyme. Because of the high apparent Km for NADH, it is postulated that the brain isoenzyme I5.9 serves to maintain glycolysis when NADH levels rise under relatively anaerobic conditions especially during fetal and neonatal development."}
{"id": "PMID:226147", "title": "Ternary complex formation of pig heart lactate dehydrogenase with spin-labelled coenzyme and inhibitors as studied by electron spin resonance.", "content": "The formation of ternary inhibitor and 'dead end' complexes of pig heart lactate dehydrogenase (L-lactate:NAD+ oxidoreductase, EC 1.1.1.27) was studied by means of two NAD derivatives, spin-labelled at N6 and C-8 of the adenine ring. Dissociation constants calculated for the inhibitors oxamate and oxalate from their corresponding ternary complexes are in excellent agreement with data from literature derived from sedimentation experiments. However, the recently postulated enzyme-NADH-sulfite complex was not observed. The mobility of the spin-label, i.e. the protein conformation near the adenine binding pocket in various ternary complexes depends on the type of inhibition or substrate employed.", "contents": "Ternary complex formation of pig heart lactate dehydrogenase with spin-labelled coenzyme and inhibitors as studied by electron spin resonance. The formation of ternary inhibitor and 'dead end' complexes of pig heart lactate dehydrogenase (L-lactate:NAD+ oxidoreductase, EC 1.1.1.27) was studied by means of two NAD derivatives, spin-labelled at N6 and C-8 of the adenine ring. Dissociation constants calculated for the inhibitors oxamate and oxalate from their corresponding ternary complexes are in excellent agreement with data from literature derived from sedimentation experiments. However, the recently postulated enzyme-NADH-sulfite complex was not observed. The mobility of the spin-label, i.e. the protein conformation near the adenine binding pocket in various ternary complexes depends on the type of inhibition or substrate employed."}
{"id": "PMID:226148", "title": "Inhibition of trypsin and chymotrypsin by thiols. Biphasic kinetics of reactivation and inhibition induced by sodium periodate addition.", "content": "Biphasic kinetic data were obtained when trypsin (EC 3.4.21.4) which had previously been complexed with a thiol-containing inhibitor (present in Ehrlich ascites tumour cells) was incubated with incremental additions of periodate. At low concentrations of periodate the trypsin was re-activated whilst at higher concentrations of periodate the trypsin was irreversibly inhibited. This biphasic reactivation followed by inhibition was also demonstrated when trypsin was first inhibited by dithiothreitol and followed by incremental addition of periodate. Similar results were obtained with chymotrypsin (EC 3.4.21.1). Incremental additions of either dithiothreitol or periodate caused inhibition of both these enzymes. The biphasic kinetic data can be explained in terms of reduction and oxidation of a significant disulphide bond in both trypsin and chymotrypsin which can be cleaved by thiols in a disulphide exchange reaction [1]. This bond is thought to maintain the active centres of each of these enzymes in a conformation sterically favourable for enzymic cleavage of specific peptide bonds in the protein substrates (polymeric collagen fibrils and casein) employed in this study.", "contents": "Inhibition of trypsin and chymotrypsin by thiols. Biphasic kinetics of reactivation and inhibition induced by sodium periodate addition. Biphasic kinetic data were obtained when trypsin (EC 3.4.21.4) which had previously been complexed with a thiol-containing inhibitor (present in Ehrlich ascites tumour cells) was incubated with incremental additions of periodate. At low concentrations of periodate the trypsin was re-activated whilst at higher concentrations of periodate the trypsin was irreversibly inhibited. This biphasic reactivation followed by inhibition was also demonstrated when trypsin was first inhibited by dithiothreitol and followed by incremental addition of periodate. Similar results were obtained with chymotrypsin (EC 3.4.21.1). Incremental additions of either dithiothreitol or periodate caused inhibition of both these enzymes. The biphasic kinetic data can be explained in terms of reduction and oxidation of a significant disulphide bond in both trypsin and chymotrypsin which can be cleaved by thiols in a disulphide exchange reaction [1]. This bond is thought to maintain the active centres of each of these enzymes in a conformation sterically favourable for enzymic cleavage of specific peptide bonds in the protein substrates (polymeric collagen fibrils and casein) employed in this study."}
{"id": "PMID:226149", "title": "Cyclic nucleotide binding properties and molecular forms of the cyclic-AMP-dependent protein kinase from bovine eye lens.", "content": "The activity of the cyclic-AMP-dependent protein kinase found in the crude extract of bovine eye lens cortical fibers was increased by 10(-6) M cyclic AMP or 10(-5) M cyclic GMP to the same extent, However, the interaction between cyclic AMP and cyclic GMP in the course of binding to the cyclic-AMP-dependent protein kinase did not seem to be competitive. Scatchard analysis of cyclic GMP binding by the crude extract indicated the presence of two type of cyclic GMP binding sites (Kd1 about 2 . (10(-7) M, Kd2 about 5 . 10(-6) M). Different species of cyclic nucleotide binding fractions were separated by Sephadex G-200 gel chromatography of the crude extract. The bulk of the low affinity cyclic GMP binding activity was found in the exclusion volume. The cyclic-AMP-dependent protein kinase eluted in two fraction (apparent molecular weight 300 000 and 150 000) and both protein kinase fractions were accompanied by the high affinity cyclic GMP binding activity. However, the ratios of this activity to the cyclic AMP binding activity were different in the two fraction, suggesting that different molecular weight forms of the holoenzyme had different cyclic nucleotide binding properties.", "contents": "Cyclic nucleotide binding properties and molecular forms of the cyclic-AMP-dependent protein kinase from bovine eye lens. The activity of the cyclic-AMP-dependent protein kinase found in the crude extract of bovine eye lens cortical fibers was increased by 10(-6) M cyclic AMP or 10(-5) M cyclic GMP to the same extent, However, the interaction between cyclic AMP and cyclic GMP in the course of binding to the cyclic-AMP-dependent protein kinase did not seem to be competitive. Scatchard analysis of cyclic GMP binding by the crude extract indicated the presence of two type of cyclic GMP binding sites (Kd1 about 2 . (10(-7) M, Kd2 about 5 . 10(-6) M). Different species of cyclic nucleotide binding fractions were separated by Sephadex G-200 gel chromatography of the crude extract. The bulk of the low affinity cyclic GMP binding activity was found in the exclusion volume. The cyclic-AMP-dependent protein kinase eluted in two fraction (apparent molecular weight 300 000 and 150 000) and both protein kinase fractions were accompanied by the high affinity cyclic GMP binding activity. However, the ratios of this activity to the cyclic AMP binding activity were different in the two fraction, suggesting that different molecular weight forms of the holoenzyme had different cyclic nucleotide binding properties."}
{"id": "PMID:226150", "title": "Stereospecificity of hydrogen transfer in the saccharopine dehydrogenase reaction.", "content": "The stereospecificity of hydrogen transfer in the synthesis of saccharopine from alpha-ketoglutarate and L-lysine catalyzed by saccharopine dehydrogenase (N5-(1,3-dicarboxypropyl)-L-lysine: NAD oxidoreductase (L-lysine-forming), EC 1.5.1.7) was examined by using [4A-3H]- and [4B-3H]NADH. The enzyme showed the A-stereospecificity. The NMR analysis of the saccharopine prepared with [4\"A-2H]NADH revealed that the label was incorporated into the C-2 of the glutaryl moiety.", "contents": "Stereospecificity of hydrogen transfer in the saccharopine dehydrogenase reaction. The stereospecificity of hydrogen transfer in the synthesis of saccharopine from alpha-ketoglutarate and L-lysine catalyzed by saccharopine dehydrogenase (N5-(1,3-dicarboxypropyl)-L-lysine: NAD oxidoreductase (L-lysine-forming), EC 1.5.1.7) was examined by using [4A-3H]- and [4B-3H]NADH. The enzyme showed the A-stereospecificity. The NMR analysis of the saccharopine prepared with [4\"A-2H]NADH revealed that the label was incorporated into the C-2 of the glutaryl moiety."}
{"id": "PMID:226151", "title": "Pulmonary phosphatidic acid phosphatase. Properties of membrane-bound phosphatidate-dependent phosphatidic acid phosphatase in rat lung.", "content": "1. The membrane-bound phosphatidate-dependent phosphatidic acid phosphatase activity of rat lung has been investigated in cytosol and microsomal fractions using as a substrate [32P]phosphatidate bound to heat inactivated rat liver microsomes. Both activities demonstrated broad pH optima with a maximum of 7.4--8 for the cytosol and a maximum of 6.5--7.5 with microsomal preparations. 2. At low concentrations (0--5 mM) Mg2+ produced a slight stimulation of the cytosol activity but at higher concentrations an inhibition was observed. Low concentrations (1.0--2.0 mM) of EDTA abolished the cytosol activity and reduced the microsomal activity to half. In both cases, the addition of Mg2+ in the presence of EDTA resulted in an activity which was more than 2-fold greater than that observed in the absence of chelator or divalent cation. 3. The cytosol activity was relatively resistant to the addition of ionic and nonionic detergents. In general, the addition of a number of phosphate esters increased rather than decreased the release of 32Pi, indicating a relative specificity for phosphate groups associated with a hydrophobic environment. The addition of aqueous dispersions of phosphatidate, lysophosphatidic acid or phosphatidylglycerophosphate markedly reduced the hydrolysis of membrane-bound [32P]phosphatidate. The cytosol activity was slightly inhibited by the addition of phosphatidylcholine. 4. In an attempt to estimate the relative contributions of the cytosol and microsomal activities in vivo, these activities were assayed using [32P]phosphatidate endogenously generated on rat lung microsomes. With the 32P-labelled microsomes, the hydrolysis remained linear over the 45 min of the experiment. Addition of high speed supernatant produced a rapid release of 32Pi during the first 10 min followed by a more gradual release similar to that oberved with the microsomes alone. The cytosol activity remained greater than the microsomal activity at all times studied. 5. When [14C]phosphatidate-labelled microsomes were incubated in the presence of nonradioactive CDPcholine, the addition of cytosol markedly stimulated the incorporation of radioactivity into phosphatidylcholine. This observation suggests that the phosphatidic acid phosphatase activity associated with the cytosol has a role in phosphatidylcholine (and presumably surfactant) biosynthesis in rat lung.", "contents": "Pulmonary phosphatidic acid phosphatase. Properties of membrane-bound phosphatidate-dependent phosphatidic acid phosphatase in rat lung. 1. The membrane-bound phosphatidate-dependent phosphatidic acid phosphatase activity of rat lung has been investigated in cytosol and microsomal fractions using as a substrate [32P]phosphatidate bound to heat inactivated rat liver microsomes. Both activities demonstrated broad pH optima with a maximum of 7.4--8 for the cytosol and a maximum of 6.5--7.5 with microsomal preparations. 2. At low concentrations (0--5 mM) Mg2+ produced a slight stimulation of the cytosol activity but at higher concentrations an inhibition was observed. Low concentrations (1.0--2.0 mM) of EDTA abolished the cytosol activity and reduced the microsomal activity to half. In both cases, the addition of Mg2+ in the presence of EDTA resulted in an activity which was more than 2-fold greater than that observed in the absence of chelator or divalent cation. 3. The cytosol activity was relatively resistant to the addition of ionic and nonionic detergents. In general, the addition of a number of phosphate esters increased rather than decreased the release of 32Pi, indicating a relative specificity for phosphate groups associated with a hydrophobic environment. The addition of aqueous dispersions of phosphatidate, lysophosphatidic acid or phosphatidylglycerophosphate markedly reduced the hydrolysis of membrane-bound [32P]phosphatidate. The cytosol activity was slightly inhibited by the addition of phosphatidylcholine. 4. In an attempt to estimate the relative contributions of the cytosol and microsomal activities in vivo, these activities were assayed using [32P]phosphatidate endogenously generated on rat lung microsomes. With the 32P-labelled microsomes, the hydrolysis remained linear over the 45 min of the experiment. Addition of high speed supernatant produced a rapid release of 32Pi during the first 10 min followed by a more gradual release similar to that oberved with the microsomes alone. The cytosol activity remained greater than the microsomal activity at all times studied. 5. When [14C]phosphatidate-labelled microsomes were incubated in the presence of nonradioactive CDPcholine, the addition of cytosol markedly stimulated the incorporation of radioactivity into phosphatidylcholine. This observation suggests that the phosphatidic acid phosphatase activity associated with the cytosol has a role in phosphatidylcholine (and presumably surfactant) biosynthesis in rat lung."}
{"id": "PMID:226152", "title": "Pulmonary phosphatidic acid phosphatase. A comparative study of the aqueously dispersed phosphatidate-dependent and membrane-bound phosphatidate-dependent phosphatidic acid phosphatase activities of rat lung.", "content": "1. The properties of the aqueously dispersed phosphatidate-dependent phosphatidic acid phosphatase (EC 3.1.3.4) activities of rat lung have been studied in microsomal and cytosol preparations and compared with the properties of the membrane-bound phosphatidate-dependent activities. 2. The microsomal phosphatidic acid phosphatase displayed a prominent pH optimum at 6.5 with a minor peak which varied between 7.5--8 in different experiments. With the cytosol, the major activity was at the higher pH (7.5--8.0) but a distinct optimum was also observed at pH 6.0--6.5. With the membrane-bound substrate, a single broad optimum was observed between pH 7.4 and 8.0 with the cytosol and 6.5--7.5 with the microsomal fraction. 3. Subcellular fractionation studies revealed that the microsomal fraction possessed the greatest proportion of the total phosphatidic acid phosphatase activity and the highest relative specific activity. However, studies with marker enzymes indicated that the aqueously dispersed phosphatidate-dependent activity could be present in plasma membrane, lysosomes and osmiophilic lamellar bodies as well as in the endoplasmic reticulum. 4. The aqueously dispersed phosphatidic acid-dependent activities present in the microsomal and supernatant fractions were inhibited by Ca2+, Mn2+, F- and by high concentrations of Mg2+. In contrast to the membrane-bound phosphatidate-dependent activities, there was little Mg2+ stimulation and only a very slight inhibitory effect was noted with EDTA. A small EDTA-dependent Mg2+ stimulation could be observed with the microsomal fraction but only at the lower pH optimum (6.5). 5. The presence of a number of phosphate esters tended to stimulate rather than inhibit the microsomal activity, indicating that the hydrolase is relatively specific for lipid substrates. Marked inhibitions were noted with lysophosphatidic acid and phosphatidylglycerol phosphate. Phosphatidylcholine produced a slight inhibition. 6. The results indicate that the bulk of the aqueously dispersed phosphatidate-dependent phosphatidic acid phosphatase activities of rat lung microsomes and cytosol is not related to the activities observed with membrane-bound phosphatidate. The Mg2+-dependent hydrolase activities may be synonymous. However, unequivocal conclusions will only be possible when the polypeptide or polypeptides responsible for these activities can be purified.", "contents": "Pulmonary phosphatidic acid phosphatase. A comparative study of the aqueously dispersed phosphatidate-dependent and membrane-bound phosphatidate-dependent phosphatidic acid phosphatase activities of rat lung. 1. The properties of the aqueously dispersed phosphatidate-dependent phosphatidic acid phosphatase (EC 3.1.3.4) activities of rat lung have been studied in microsomal and cytosol preparations and compared with the properties of the membrane-bound phosphatidate-dependent activities. 2. The microsomal phosphatidic acid phosphatase displayed a prominent pH optimum at 6.5 with a minor peak which varied between 7.5--8 in different experiments. With the cytosol, the major activity was at the higher pH (7.5--8.0) but a distinct optimum was also observed at pH 6.0--6.5. With the membrane-bound substrate, a single broad optimum was observed between pH 7.4 and 8.0 with the cytosol and 6.5--7.5 with the microsomal fraction. 3. Subcellular fractionation studies revealed that the microsomal fraction possessed the greatest proportion of the total phosphatidic acid phosphatase activity and the highest relative specific activity. However, studies with marker enzymes indicated that the aqueously dispersed phosphatidate-dependent activity could be present in plasma membrane, lysosomes and osmiophilic lamellar bodies as well as in the endoplasmic reticulum. 4. The aqueously dispersed phosphatidic acid-dependent activities present in the microsomal and supernatant fractions were inhibited by Ca2+, Mn2+, F- and by high concentrations of Mg2+. In contrast to the membrane-bound phosphatidate-dependent activities, there was little Mg2+ stimulation and only a very slight inhibitory effect was noted with EDTA. A small EDTA-dependent Mg2+ stimulation could be observed with the microsomal fraction but only at the lower pH optimum (6.5). 5. The presence of a number of phosphate esters tended to stimulate rather than inhibit the microsomal activity, indicating that the hydrolase is relatively specific for lipid substrates. Marked inhibitions were noted with lysophosphatidic acid and phosphatidylglycerol phosphate. Phosphatidylcholine produced a slight inhibition. 6. The results indicate that the bulk of the aqueously dispersed phosphatidate-dependent phosphatidic acid phosphatase activities of rat lung microsomes and cytosol is not related to the activities observed with membrane-bound phosphatidate. The Mg2+-dependent hydrolase activities may be synonymous. However, unequivocal conclusions will only be possible when the polypeptide or polypeptides responsible for these activities can be purified."}
{"id": "PMID:226153", "title": "Synthesis and content of ether-linked glycerophospholipids in the harderian gland of rabbits.", "content": "Although harderian glands are rich in neutral glycerolipids with ether bonds, less than 20% of the choline glycerophospholipids have ether bonds in the white and pink portions of the adult rabbit harderian gland. Only 6% of these are plasmalogens while 94% are alkylacyl glycerophosphocholines. The ethanolamine glycerophospholipids include 37% with ether bonds in both white and pink portions. In the white portion 96% are plasmalogens but only 19% are plasmalogens in the pink portion. The microsomal ethanolaminephosphotransferase (EC 2.7.8.1) is more active with diacylglycerols than with alkylacylglycerols. The microsomal cholinephosphotransferase (EC 2.7.8.2) is equally active with both diradylglycerols. Particularly with microsomes from the pink portion, the apparent Km values for CDPethanolamine and CDPcholine are ower in the presence of alkylacylglycerols than in the presence of diacylglycerols. The incorporation of radioactivity from CDP[14C]ethanolamine and CDP[14C]choline into ethanolamine and choline plasmalogens was increased several-fold by addition of alkylacylglycerols but was not increased substantially by addition of diacylglycerols.", "contents": "Synthesis and content of ether-linked glycerophospholipids in the harderian gland of rabbits. Although harderian glands are rich in neutral glycerolipids with ether bonds, less than 20% of the choline glycerophospholipids have ether bonds in the white and pink portions of the adult rabbit harderian gland. Only 6% of these are plasmalogens while 94% are alkylacyl glycerophosphocholines. The ethanolamine glycerophospholipids include 37% with ether bonds in both white and pink portions. In the white portion 96% are plasmalogens but only 19% are plasmalogens in the pink portion. The microsomal ethanolaminephosphotransferase (EC 2.7.8.1) is more active with diacylglycerols than with alkylacylglycerols. The microsomal cholinephosphotransferase (EC 2.7.8.2) is equally active with both diradylglycerols. Particularly with microsomes from the pink portion, the apparent Km values for CDPethanolamine and CDPcholine are ower in the presence of alkylacylglycerols than in the presence of diacylglycerols. The incorporation of radioactivity from CDP[14C]ethanolamine and CDP[14C]choline into ethanolamine and choline plasmalogens was increased several-fold by addition of alkylacylglycerols but was not increased substantially by addition of diacylglycerols."}
{"id": "PMID:226154", "title": "The effect of serum lipoproteins on cholesterol content and sterol exchange in cultured human endothelial cells.", "content": "Cultured human endothelial cells preincubated with the infranatant of human serum increased their content of cholesterol when subsequently exposed to low density lipoproteins (LDL) as compared to control cultures further incubated in the presence of infranatant only. Replacing LDL with high density lipoproteins (HDL) resulted in no change in the cellular cholesterol content compared to the control. The addition of HDL did not influence the increase in cellular cholesterol content mediated by LDL. HDL stimulated the efflux of endogenously synthesized 14C-labelled sterols compared to the infranatant fraction, whereas LDL had only a slight effect. Cells preincubated with whole serum did not change their cholesterol content when subsequently exposed to LDL, compared to cultures further incubated in presence of whole serum. Replacing whole serum (during the final incubation) with infranatant, resulted in a decrease of the cellular cholesterol content, which was not influenced by further addition of HDL.", "contents": "The effect of serum lipoproteins on cholesterol content and sterol exchange in cultured human endothelial cells. Cultured human endothelial cells preincubated with the infranatant of human serum increased their content of cholesterol when subsequently exposed to low density lipoproteins (LDL) as compared to control cultures further incubated in the presence of infranatant only. Replacing LDL with high density lipoproteins (HDL) resulted in no change in the cellular cholesterol content compared to the control. The addition of HDL did not influence the increase in cellular cholesterol content mediated by LDL. HDL stimulated the efflux of endogenously synthesized 14C-labelled sterols compared to the infranatant fraction, whereas LDL had only a slight effect. Cells preincubated with whole serum did not change their cholesterol content when subsequently exposed to LDL, compared to cultures further incubated in presence of whole serum. Replacing whole serum (during the final incubation) with infranatant, resulted in a decrease of the cellular cholesterol content, which was not influenced by further addition of HDL."}
{"id": "PMID:226155", "title": "Regulation of sterol synthesis in human lymphocytes: evidence for post-transcriptional control by low density lipoprotein.", "content": "The effect of cordycepin (3'-deoxyadenosine), an inhibitor of messenger RNA synthesis, on the induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase mediated by lipid-depleted serum was studied in isolated human lymphocytes. 50 micrograms/ml cordycepin, although inhibiting messenger RNA synthesis by more than 50%, had no inhibitory effect on the two and four-fold induction of hydroxymethylglutaryl-CoA reductase when cells were incubated in a medium containing lipid-depleted serum for 8 and 16 h, respectively. This result suggests that newly synthesises messenger RNA is not required for the effect of lipid-depleted serum on the induction of hydroxymethylglutaryl-CoA reductase in human lymphocytes.", "contents": "Regulation of sterol synthesis in human lymphocytes: evidence for post-transcriptional control by low density lipoprotein. The effect of cordycepin (3'-deoxyadenosine), an inhibitor of messenger RNA synthesis, on the induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase mediated by lipid-depleted serum was studied in isolated human lymphocytes. 50 micrograms/ml cordycepin, although inhibiting messenger RNA synthesis by more than 50%, had no inhibitory effect on the two and four-fold induction of hydroxymethylglutaryl-CoA reductase when cells were incubated in a medium containing lipid-depleted serum for 8 and 16 h, respectively. This result suggests that newly synthesises messenger RNA is not required for the effect of lipid-depleted serum on the induction of hydroxymethylglutaryl-CoA reductase in human lymphocytes."}
{"id": "PMID:226156", "title": "Cell triacylglycerol accumulation from very low density lipoproteins isolated from normal and hypertriglyceridemic human sera.", "content": "Human fibroblast cells in culture increased their intracellular triacylglycerol levels when exposed to very low density lipoproteins (VLDL) isolated from human plasma. This response was dependent on the amount of VLDL added. VLDL from normal, type IV or type V sera gave similar results. Lipoprotein lipase enhanced this intracellular triacylglycerol accumulation. It was concluded that human fibroblast cells in culture have at least two mechanisms for triacylglycerol uptake from VLDL: (1) uptake from intact lipoprotein either by surface transfer of lipoprotein lipid or internalization of the entire lipoprotein particle, and (2) re-esterification of lower glyceride and fatty acids released by lipoprotein lipase degradation of VLDL.", "contents": "Cell triacylglycerol accumulation from very low density lipoproteins isolated from normal and hypertriglyceridemic human sera. Human fibroblast cells in culture increased their intracellular triacylglycerol levels when exposed to very low density lipoproteins (VLDL) isolated from human plasma. This response was dependent on the amount of VLDL added. VLDL from normal, type IV or type V sera gave similar results. Lipoprotein lipase enhanced this intracellular triacylglycerol accumulation. It was concluded that human fibroblast cells in culture have at least two mechanisms for triacylglycerol uptake from VLDL: (1) uptake from intact lipoprotein either by surface transfer of lipoprotein lipid or internalization of the entire lipoprotein particle, and (2) re-esterification of lower glyceride and fatty acids released by lipoprotein lipase degradation of VLDL."}
{"id": "PMID:226157", "title": "Utilization of endogenous diacylglycerol for the synthesis of triacylglycerol, phosphatidylcholine and phosphatidylethanolamine by lipid particles from baker's yeast (Saccharomyces cerevisiae).", "content": "The activity of the enzymes diacylglycerol acyltransferase (EC 2.3.1.20), cholinephosphotransferase (EC 2.7.8.2) and ethanolaminephosphotransferase (EC 2.7.8.1) have been measured in a lipid particle preparation from baker's yeast (Saccharomyces cerevisiae) with endogenous 1,2-diacylglycerol as substrate. For all three enzymes the rate of diacylglycerol utilization was established with respect to substrate and Mg2+ concentration. Neither of the enzyme activities was stimulated significantly by addition of diacylglycerols. The conversion of diacylglycerol into triacylglycerol in the presence of CDP-choline and CDPethanolamine, and the synthesis of phospholipids in the presence of acyl-CoA either added or generated in situ were studied. Neither CDPcholine nor CDPethanolamine had an effect on triacylglycerol synthesis. Exogenous acyl-CoA had no effect on either choline- or ethanolaminephosphotransferase activity. However, when the necessary substrates for formation of acyl-CoAs in situ (ATP, CoA, Mg2+ and free fatty acids) were added a decrease in both cholinephosphotransferase and ethanolaminephosphotransferase activity was observed. This inhibition was shown to be due to ATP and might explained as a result of chelation of the Mg2+, a necessary activator of both the choline- and the ethanolaminephosphotransferase.", "contents": "Utilization of endogenous diacylglycerol for the synthesis of triacylglycerol, phosphatidylcholine and phosphatidylethanolamine by lipid particles from baker's yeast (Saccharomyces cerevisiae). The activity of the enzymes diacylglycerol acyltransferase (EC 2.3.1.20), cholinephosphotransferase (EC 2.7.8.2) and ethanolaminephosphotransferase (EC 2.7.8.1) have been measured in a lipid particle preparation from baker's yeast (Saccharomyces cerevisiae) with endogenous 1,2-diacylglycerol as substrate. For all three enzymes the rate of diacylglycerol utilization was established with respect to substrate and Mg2+ concentration. Neither of the enzyme activities was stimulated significantly by addition of diacylglycerols. The conversion of diacylglycerol into triacylglycerol in the presence of CDP-choline and CDPethanolamine, and the synthesis of phospholipids in the presence of acyl-CoA either added or generated in situ were studied. Neither CDPcholine nor CDPethanolamine had an effect on triacylglycerol synthesis. Exogenous acyl-CoA had no effect on either choline- or ethanolaminephosphotransferase activity. However, when the necessary substrates for formation of acyl-CoAs in situ (ATP, CoA, Mg2+ and free fatty acids) were added a decrease in both cholinephosphotransferase and ethanolaminephosphotransferase activity was observed. This inhibition was shown to be due to ATP and might explained as a result of chelation of the Mg2+, a necessary activator of both the choline- and the ethanolaminephosphotransferase."}
{"id": "PMID:226158", "title": "Low density lipoprotein receptors and catabolism in primary cultures of rabbit hepatocytes.", "content": "Rabbit 125I-labelled low density lipoproteins (LDL) were incubated with primary monolayer cultures of rabbit hepatocytes in studies designed to assess the role of liver in LDL catabolism at the cellular level. After hepatocytes were preincubated for 20 h in lipoprotein-free medium, they exhibited time- and concentration-dependent interaction with 125I-labelled DLD at concentrations to 1 mg LDL protein/ml and times to 24 h. After a 3 h (37 degrees C) incubation with 50 microgram LDL protein/ml, hepatocytes bound 400 ng (LDL protein)/mg (cell protein), internalized 280 ng/mg, and degraded 660 ng/mg. Internalization and degradation may be greater than indicated by these values since pulse studies suggested the presence of a deiodinase which attacks cell associated 125I-labelled LDL. The amounts of LDL bound to hepatocytes after 3 h (37 degrees C) were similar to amounts for fibroblasts, but DLD internalization and degradation were considerably less. Rabbit hyperlipidemic 125I-labelled DLD showed the same amount of binding but 1.39 times more internalization and degradation than normolipidemic 125I-labelled LDL. Binding of both control and hyperlipidemic LDL was 3-fold greater at 24 and 42 h than at O or 3 h but addition of a 50-fold molar excess of high density lipoproteins (HDL) prevented increased LDL binding with time. Induction of specific high affinity receptors for binding LDL was shown to occur by preincubation of hepatocytes for increasing periods in lipoprotein-free medium and then measuring 125I-labelled LDL binding at 4 degrees C in the presence and absence of excess unlabelled LDL. Finally, hepatocytes took up 40 times more LDL than sucrose or dextran over a 24-h period, an indication that the uptake of LDL occurs via some mechanism other than simple bulk fluid endocytosis.", "contents": "Low density lipoprotein receptors and catabolism in primary cultures of rabbit hepatocytes. Rabbit 125I-labelled low density lipoproteins (LDL) were incubated with primary monolayer cultures of rabbit hepatocytes in studies designed to assess the role of liver in LDL catabolism at the cellular level. After hepatocytes were preincubated for 20 h in lipoprotein-free medium, they exhibited time- and concentration-dependent interaction with 125I-labelled DLD at concentrations to 1 mg LDL protein/ml and times to 24 h. After a 3 h (37 degrees C) incubation with 50 microgram LDL protein/ml, hepatocytes bound 400 ng (LDL protein)/mg (cell protein), internalized 280 ng/mg, and degraded 660 ng/mg. Internalization and degradation may be greater than indicated by these values since pulse studies suggested the presence of a deiodinase which attacks cell associated 125I-labelled LDL. The amounts of LDL bound to hepatocytes after 3 h (37 degrees C) were similar to amounts for fibroblasts, but DLD internalization and degradation were considerably less. Rabbit hyperlipidemic 125I-labelled DLD showed the same amount of binding but 1.39 times more internalization and degradation than normolipidemic 125I-labelled LDL. Binding of both control and hyperlipidemic LDL was 3-fold greater at 24 and 42 h than at O or 3 h but addition of a 50-fold molar excess of high density lipoproteins (HDL) prevented increased LDL binding with time. Induction of specific high affinity receptors for binding LDL was shown to occur by preincubation of hepatocytes for increasing periods in lipoprotein-free medium and then measuring 125I-labelled LDL binding at 4 degrees C in the presence and absence of excess unlabelled LDL. Finally, hepatocytes took up 40 times more LDL than sucrose or dextran over a 24-h period, an indication that the uptake of LDL occurs via some mechanism other than simple bulk fluid endocytosis."}
{"id": "PMID:226159", "title": "Uptake and degradation of 125I-labelled high density lipoproteins in rat liver cells in vivo and in vitro.", "content": "1. The uptake of 125I-labelled high density lipoproteins (HDL) in various organs of the rat was determined after an intravenous injection. The uptake of 125I-labelled polyvinylpyrrolidone in the same organs was determined in order to assess uptake by fluid endocytosis. The uptake/organ was highest for the liver. The adrenals showed the highest uptake/unit weight of the organs studied. The liver, the kidneys and the spleen showed comparable values for uptake/g of tissue. The uptake of 125I-labelled HDL exceeded by far that of 125I-labelled polyvinylpyrrolidone in the liver, the kidneys, the spleen and the adrenals, indicating that the uptake of 125I-labelled HDL was mediated by adsorptive endocytosis. 2. The in vivo uptake of 125I-labelled HDL was determined in purified hepatocytes and non-parenchymal cells prepared by collagenase perfusion of livers from animals after intravenous injections of 125I-labelled HDL. When expressed per cell, the hepatocytes and the non-parenchymal liver cells took up about the same amount of 125I-labelled HDL. 3. The in vitro uptake and degradation of 125I-labelled HDL in isolated rat hepatocytes was studied. The uptake at increasing concentrations of 125I-labelled HDL was saturable indicating uptake mediated through binding sites. 125I-labelled HDL were easily degraded by contaminating proteases from the perfusate. 4. Subcellular fractionation by isopycnic centrifugation indicated that the accumulation of 125I-labelled HDL did not take place in the lysosomes, but rather on the plasma membrane and possibly in the endosomes (phagosomes). 5. 125I-labelled HDL were internalized into the cells and degraded in the lysosomes. Leupetin and chloroquine, inhibitors of the lysosomal function effectively inhibited the formation of 125I-labelled acid-soluble radioactivity by the cells. Chloroquine, but not the protease inhibitor leupeptin, reduced the hydrolysis of the cholesteryl ester moiety of HDL.", "contents": "Uptake and degradation of 125I-labelled high density lipoproteins in rat liver cells in vivo and in vitro. 1. The uptake of 125I-labelled high density lipoproteins (HDL) in various organs of the rat was determined after an intravenous injection. The uptake of 125I-labelled polyvinylpyrrolidone in the same organs was determined in order to assess uptake by fluid endocytosis. The uptake/organ was highest for the liver. The adrenals showed the highest uptake/unit weight of the organs studied. The liver, the kidneys and the spleen showed comparable values for uptake/g of tissue. The uptake of 125I-labelled HDL exceeded by far that of 125I-labelled polyvinylpyrrolidone in the liver, the kidneys, the spleen and the adrenals, indicating that the uptake of 125I-labelled HDL was mediated by adsorptive endocytosis. 2. The in vivo uptake of 125I-labelled HDL was determined in purified hepatocytes and non-parenchymal cells prepared by collagenase perfusion of livers from animals after intravenous injections of 125I-labelled HDL. When expressed per cell, the hepatocytes and the non-parenchymal liver cells took up about the same amount of 125I-labelled HDL. 3. The in vitro uptake and degradation of 125I-labelled HDL in isolated rat hepatocytes was studied. The uptake at increasing concentrations of 125I-labelled HDL was saturable indicating uptake mediated through binding sites. 125I-labelled HDL were easily degraded by contaminating proteases from the perfusate. 4. Subcellular fractionation by isopycnic centrifugation indicated that the accumulation of 125I-labelled HDL did not take place in the lysosomes, but rather on the plasma membrane and possibly in the endosomes (phagosomes). 5. 125I-labelled HDL were internalized into the cells and degraded in the lysosomes. Leupetin and chloroquine, inhibitors of the lysosomal function effectively inhibited the formation of 125I-labelled acid-soluble radioactivity by the cells. Chloroquine, but not the protease inhibitor leupeptin, reduced the hydrolysis of the cholesteryl ester moiety of HDL."}
{"id": "PMID:226160", "title": "Circular dichroism studies on cytochrome c peroxidase and cytochrome c-551 of Pseudomonas aeruginosa.", "content": "Circular dichroism (CD) spectra of ferric, ferrous and ferrous-carbonyl forms of Pseudomonas cytochrome c peroxidase have been recorded in the wave length range 200 to 650 nm. CD spectra in the Soret region show that in the oxidized enzyme the two hemes are degenerate, whereas in the reduced form the hemes are perturbed differently and one of the hemes appears to be non-degenerate. Changes in optical activity upon formation of the carbonylderivative suggest a spin-state conversion and indicate the presence of one high-spin and a low-spin heme. A histidine residue is proposed for the axial ligand of the heme iron. The alpha-helical content of the enzyme is estimated to be 34%. Ligand binding or changes in the oxidation state of the heme iron do not alter the conformation of the protein backbone. The dichroic spectra of oxidized and reduced cytochrome c-551 (P. aeruginosa) are included for comparison. In the visible region the cytochrome exhibits CD spectra similar to those of the peroxidase, whereas in the Soret region the dichroic spectra of the cytochrome are simpler. CD spectra in the far-ultraviolet region show the cytochrome to have a high alpha-helix content.", "contents": "Circular dichroism studies on cytochrome c peroxidase and cytochrome c-551 of Pseudomonas aeruginosa. Circular dichroism (CD) spectra of ferric, ferrous and ferrous-carbonyl forms of Pseudomonas cytochrome c peroxidase have been recorded in the wave length range 200 to 650 nm. CD spectra in the Soret region show that in the oxidized enzyme the two hemes are degenerate, whereas in the reduced form the hemes are perturbed differently and one of the hemes appears to be non-degenerate. Changes in optical activity upon formation of the carbonylderivative suggest a spin-state conversion and indicate the presence of one high-spin and a low-spin heme. A histidine residue is proposed for the axial ligand of the heme iron. The alpha-helical content of the enzyme is estimated to be 34%. Ligand binding or changes in the oxidation state of the heme iron do not alter the conformation of the protein backbone. The dichroic spectra of oxidized and reduced cytochrome c-551 (P. aeruginosa) are included for comparison. In the visible region the cytochrome exhibits CD spectra similar to those of the peroxidase, whereas in the Soret region the dichroic spectra of the cytochrome are simpler. CD spectra in the far-ultraviolet region show the cytochrome to have a high alpha-helix content."}
{"id": "PMID:226161", "title": "Protected natural peptides as intermediates for preparing semisynthetic peptides and protein analogs. Selective acylation of epsilon-amino groups in cyanogen bromide peptides of cytochrome c using azidoformates.", "content": "Treatment of CNBr peptides 66--80, 81--104 and 66--104 from cytochrome c with t-butyloxycarbonyl azide leads to selective acylation of the epsilon-amino groups of lysine residues and the phenolic hydroxyl groups of tyrosine residues with less than 25% acylation of the alpha-amino groups. Similar selectivity was obtained for reactions of benzyloxycarbonyl azide, p-nitrobenzyloxycarbonyl azide and p-methoxybenzyloxycarbonyl azide with peptide 81--104. All of these protective groups can be removed under mild conditions, and thus, the partially protected natural peptides are desirable intermediates for the preparation of semisynthetic peptides. Model condensation reactions of N alpha t-butyloxycarbonyl methionine N-hydroxysuccinimide ester with Z-protected peptide 81--104 produced a peptide corresponding to residues 80 to 104 of cytochrome c in 94% yield.", "contents": "Protected natural peptides as intermediates for preparing semisynthetic peptides and protein analogs. Selective acylation of epsilon-amino groups in cyanogen bromide peptides of cytochrome c using azidoformates. Treatment of CNBr peptides 66--80, 81--104 and 66--104 from cytochrome c with t-butyloxycarbonyl azide leads to selective acylation of the epsilon-amino groups of lysine residues and the phenolic hydroxyl groups of tyrosine residues with less than 25% acylation of the alpha-amino groups. Similar selectivity was obtained for reactions of benzyloxycarbonyl azide, p-nitrobenzyloxycarbonyl azide and p-methoxybenzyloxycarbonyl azide with peptide 81--104. All of these protective groups can be removed under mild conditions, and thus, the partially protected natural peptides are desirable intermediates for the preparation of semisynthetic peptides. Model condensation reactions of N alpha t-butyloxycarbonyl methionine N-hydroxysuccinimide ester with Z-protected peptide 81--104 produced a peptide corresponding to residues 80 to 104 of cytochrome c in 94% yield."}
{"id": "PMID:226162", "title": "Semisynthetic analogs of cytochrome c reconstructed from natural and synthetic peptides.", "content": "A biologically active semisynthetic hybrid of horse heart cytochrome c has been prepared by combining the heme peptide 1 through 65 (HP 1-65), prepared by CNBr cleavage of natural cytochrome c, with a semisynthetic peptide corresponding to positions 66 through 104. A fully protected synthetic peptide 66--79 was prepared by a modified solid phase peptide synthesis procedure and was converted to its N-hydroxysuccinimide ester. A peptide corresponding to residues 81--104 of cytochrome c was also isolated from the CNBr cleavage mixture and its epsilon-amino groups and tyrosyl hydroxyl group were protected selectively with the t-butyloxycarbonyl group. This partially protected peptide was reacted with t-butyloxycarbonyl methionine N-hydroxysuccinimide ester to give a derivative having methionine at position 80. This product was deprotected, purified and then t-butyloxycarbonyl groups were again introduced specifically on the epsilon-amino groups to give the peptide, Boc(Lys,Tyr)80--104. A semisynthetic peptide corresponding to residues 66 through 104 of cytochrome c was prepared by condensing the synthetic peptide 66--79 N-hydroxysuccinimide ester with t-butyloxycarbonyl (Lys,Tyr)80--104. The semisynthetic product was deprotected, purified and combined under anaerobic conditions with a heme peptide, HP 1-65, that was isolated from the products of CNBr cleavage of native cytochrome c. The reconstituted semisynthetic cytochrome c was purified by ion exchange chromatography and was shown to have the same oxygen uptake as native cytochrome c when assayed in the succinate oxidase system.", "contents": "Semisynthetic analogs of cytochrome c reconstructed from natural and synthetic peptides. A biologically active semisynthetic hybrid of horse heart cytochrome c has been prepared by combining the heme peptide 1 through 65 (HP 1-65), prepared by CNBr cleavage of natural cytochrome c, with a semisynthetic peptide corresponding to positions 66 through 104. A fully protected synthetic peptide 66--79 was prepared by a modified solid phase peptide synthesis procedure and was converted to its N-hydroxysuccinimide ester. A peptide corresponding to residues 81--104 of cytochrome c was also isolated from the CNBr cleavage mixture and its epsilon-amino groups and tyrosyl hydroxyl group were protected selectively with the t-butyloxycarbonyl group. This partially protected peptide was reacted with t-butyloxycarbonyl methionine N-hydroxysuccinimide ester to give a derivative having methionine at position 80. This product was deprotected, purified and then t-butyloxycarbonyl groups were again introduced specifically on the epsilon-amino groups to give the peptide, Boc(Lys,Tyr)80--104. A semisynthetic peptide corresponding to residues 66 through 104 of cytochrome c was prepared by condensing the synthetic peptide 66--79 N-hydroxysuccinimide ester with t-butyloxycarbonyl (Lys,Tyr)80--104. The semisynthetic product was deprotected, purified and combined under anaerobic conditions with a heme peptide, HP 1-65, that was isolated from the products of CNBr cleavage of native cytochrome c. The reconstituted semisynthetic cytochrome c was purified by ion exchange chromatography and was shown to have the same oxygen uptake as native cytochrome c when assayed in the succinate oxidase system."}
{"id": "PMID:226163", "title": "The iron-sulphur centres of soluble hydrogenase from Alcaligenes eutrophus.", "content": "The soluble hydrogenase (hydrogen:NAD+ oxidoreductase (EC 1.12.1.2) from Alcaligenes eutrophus has been purified to homogeneity by an improved procedure, which includes preparative electrophoresis as final step. The specific activity of 57 mumol H2 oxidized/min per mg protein was achieved and the yield of pure enzyme from 200 g cells (wet weight) was about 16 mg/purification. After removal of non-functional iron, analysis of iron and acid-labile sulphur yielded average values of 11.5 and 12.9 atoms/molecule of enzyme, respectively. p-Chloromercuribenzoate was a strong inhibitor of hydrogenase and apparently competed with NAD not with H2. Chelating agents, CO and O2 failed to inhibit enzyme activity. The oxidized hydrogenase showed an EPR spectrum with a small signal at g = 2.02. On reduction the appearance of a high temperature (50--77 K) signal at g = 2.04, 1.95 and a more complex low temperature (less than 30 K) spectrum at g = 2.04, 2.0, 1.95, 1.93, 1.86 was observed. The pronounced temperature dependence and characteristic lineshape of the signals obtained with hydrogenase in 80--85% dimethylsulphoxide demonstrated that iron-sulphur centres of both the [2Fe-2S] and [4Fe-4S] types are present in the enzyme. Quantitation of the EPR signals indicated the existence of two identical centres each of the [4Fe-4S] and of the [2Fe-2S] type. The midpoint redox potentials of the [4Fe-4S] and the [2Fe-2S] centres were determined to be -445 mV and -325 mV, respectively. Spin coupling between two centres, indicated by the split feature of the low temperature spectrum of the native hydrogenase around g = 1.95, 1.93, has been established by power saturation studies. On reduction of the [Fe-4S] centres, the electron spin relaxation rate of the [2Fe-2S] centres was considerably increased. Treatment of hydrogenase with CO caused no change in EPR spectra.", "contents": "The iron-sulphur centres of soluble hydrogenase from Alcaligenes eutrophus. The soluble hydrogenase (hydrogen:NAD+ oxidoreductase (EC 1.12.1.2) from Alcaligenes eutrophus has been purified to homogeneity by an improved procedure, which includes preparative electrophoresis as final step. The specific activity of 57 mumol H2 oxidized/min per mg protein was achieved and the yield of pure enzyme from 200 g cells (wet weight) was about 16 mg/purification. After removal of non-functional iron, analysis of iron and acid-labile sulphur yielded average values of 11.5 and 12.9 atoms/molecule of enzyme, respectively. p-Chloromercuribenzoate was a strong inhibitor of hydrogenase and apparently competed with NAD not with H2. Chelating agents, CO and O2 failed to inhibit enzyme activity. The oxidized hydrogenase showed an EPR spectrum with a small signal at g = 2.02. On reduction the appearance of a high temperature (50--77 K) signal at g = 2.04, 1.95 and a more complex low temperature (less than 30 K) spectrum at g = 2.04, 2.0, 1.95, 1.93, 1.86 was observed. The pronounced temperature dependence and characteristic lineshape of the signals obtained with hydrogenase in 80--85% dimethylsulphoxide demonstrated that iron-sulphur centres of both the [2Fe-2S] and [4Fe-4S] types are present in the enzyme. Quantitation of the EPR signals indicated the existence of two identical centres each of the [4Fe-4S] and of the [2Fe-2S] type. The midpoint redox potentials of the [4Fe-4S] and the [2Fe-2S] centres were determined to be -445 mV and -325 mV, respectively. Spin coupling between two centres, indicated by the split feature of the low temperature spectrum of the native hydrogenase around g = 1.95, 1.93, has been established by power saturation studies. On reduction of the [Fe-4S] centres, the electron spin relaxation rate of the [2Fe-2S] centres was considerably increased. Treatment of hydrogenase with CO caused no change in EPR spectra."}
{"id": "PMID:226164", "title": "Oxidation-reduction reactions of copper-thiolate centres in Cu-thionein.", "content": "Cu-thionein from yeast was investigated by EPR spectroscopy to probe the oxidation state of copper, and the effects on it of oxidizing and reducing agents. At pH 0.2 the copper was released, but no EPR signal from Cu(II) was observed, unless air was present. Optical experiments did not detect any disulphide groups which might have been formed during anaerobic release of copper. The mercurial, p-hydroxymercuribenzoate caused the release of EPR-detectable copper only under aerobic conditions, and EDTA caused release of Cu(II) on heating. No reduction of the copper-thiolate units in Cu-thionein by ascorbate was detected. Potentiometric titrations with hexachloroiridate(IV) or hexacyanoferrate(III) produced several different Cu(II) EPR signals at various stages of oxidation. The former oxidizing agent required a lower oxidation-reduction potential (+350 mV) to oxidize the copper, than the latter (+410 mV) and neither titration was fully reversible. The EPR signal from Cu(II) oxidized by hexachloroiridate(IV) resembled that produced by p-hydroxy-mercuribenzoate in air, suggesting that the copper was released from its thiolate ligands. It is concluded that the EPR non-detectable copper in the native protein is Cu(I). Oxidation-reduction of the copper-thiolate clusters of Cu-thionein is proposed to be decisive for controlling storage and transport of cellular copper.", "contents": "Oxidation-reduction reactions of copper-thiolate centres in Cu-thionein. Cu-thionein from yeast was investigated by EPR spectroscopy to probe the oxidation state of copper, and the effects on it of oxidizing and reducing agents. At pH 0.2 the copper was released, but no EPR signal from Cu(II) was observed, unless air was present. Optical experiments did not detect any disulphide groups which might have been formed during anaerobic release of copper. The mercurial, p-hydroxymercuribenzoate caused the release of EPR-detectable copper only under aerobic conditions, and EDTA caused release of Cu(II) on heating. No reduction of the copper-thiolate units in Cu-thionein by ascorbate was detected. Potentiometric titrations with hexachloroiridate(IV) or hexacyanoferrate(III) produced several different Cu(II) EPR signals at various stages of oxidation. The former oxidizing agent required a lower oxidation-reduction potential (+350 mV) to oxidize the copper, than the latter (+410 mV) and neither titration was fully reversible. The EPR signal from Cu(II) oxidized by hexachloroiridate(IV) resembled that produced by p-hydroxy-mercuribenzoate in air, suggesting that the copper was released from its thiolate ligands. It is concluded that the EPR non-detectable copper in the native protein is Cu(I). Oxidation-reduction of the copper-thiolate clusters of Cu-thionein is proposed to be decisive for controlling storage and transport of cellular copper."}
{"id": "PMID:226165", "title": "(Na+ + K+)-ATPase: effects of detergents on the cross-linking of subunits in the presence of Cu2+ and o-phenanthroline.", "content": "When (Na+ + K+)-ATPase is reacted with Cu2+ or Cu2+-phenanthroline, cross-linking of the two subunits (alpha and beta) occurs. The major products are alpha,beta- and alpha,alpha-dimers. The alpha,beta-dimer is unstable in the presence of EDTA, but becomes stable when it is first exposed to digitonin or Triton X-100. Conversion of alpha-CU2+-beta to alpha-S-S-beta is suggested. If the enzyme that is pretreated with these detergents is used, only the stable alpha,beta-dimer is obtained, and the formation of alpha,alpha-dimer is inhibited. The data are consistent with alpha 2 beta 2 quaternary structure of the enzyme.", "contents": "(Na+ + K+)-ATPase: effects of detergents on the cross-linking of subunits in the presence of Cu2+ and o-phenanthroline. When (Na+ + K+)-ATPase is reacted with Cu2+ or Cu2+-phenanthroline, cross-linking of the two subunits (alpha and beta) occurs. The major products are alpha,beta- and alpha,alpha-dimers. The alpha,beta-dimer is unstable in the presence of EDTA, but becomes stable when it is first exposed to digitonin or Triton X-100. Conversion of alpha-CU2+-beta to alpha-S-S-beta is suggested. If the enzyme that is pretreated with these detergents is used, only the stable alpha,beta-dimer is obtained, and the formation of alpha,alpha-dimer is inhibited. The data are consistent with alpha 2 beta 2 quaternary structure of the enzyme."}
{"id": "PMID:226166", "title": "In vitro characterization of skeletal muscle beta-adrenergic receptors coupled to adenylate cyclase.", "content": "[3H]Dihydroalprenolol, a potent beta-adrenergic antagonist, was used to identify the adenylate cyclase-coupled beta-adrenoceptors in isolated membranes of rat skeletal muscle. The receptor sites, as revealed by [3H]dihydroalprenolol binding, were predominantly localized in plasmalemmal fraction. That skeletal muscle fraction may also contain the plasmalemma of other intramuscular cells, especially that of blood vessels. Hence, the [3H]dihydroalprenolol binding observed in that fraction may be due partly to its binding to the plasmalemma of blood vessels. Small but consistent binding was also observed in sarcoplasmic reticulum and mitochondria. The level of [3H]dihydroalprenolol binding in different subcellular fractions closely correlated with the level of adenylate cyclase present in those fractions. The binding of [3H]dihydroalprenolol to plasmalemma exhibited saturation kinetics. The binding was rapid, reaching equilibrium within 5 min, and it was readily dissociable. From the kinetics of binding, association (K1) and dissociation (K2) rate constants of 2.21 . 10(7) M-1 . min-1 and 3.21 . 10(-1) min-1, respectively, were obtained. The dissociation constant (Kd) of 15 mM for [3H]dihydroalprenolol obtained from saturation binding data closely agreed with the Kd derived from the ratio of dissociation and association rate constants (K2/K1). Several beta-adrenergic agents known to be active on intact skeletal muscle also competed for [3H]dihydroalprenolol binding sites in isolated plasmalemma with essentially similar selectivity and stereospecificity. Catecholamines competed for [3H]dihydroalprenolol binding sites with a potency of isoproterenol greater than epinephrine greater than norepinephrine. A similar order of potency was noted for catecholamines in the activation of adenylate cyclase. Effects of catecholamines were stereospecific, (-)-isomers being more potent than (+)-isomers. Phenylephrine, an alpha-adrenergic agonist, showed no effect either on [3H]dihydroalprenolol binding or on adenylate cyclase. Known beta-adrenergic antagonists, propranolol and alprenolol, stereospecifically inhibited the [3H]dihydroalprenolol binding and the isoproterenol-stimulated adenylate cyclase. The Ki values for the antagonists determined from inhibition of [3H]dihydroalprenolol binding agreed closely with the Ki values obtained from the inhibition of adenylate cyclase. The data suggest that the binding of [3H]dihydroalprenolol in skeletal muscle membranes possess the characteristics of a substance binding to the beta-adrenergic receptor.", "contents": "In vitro characterization of skeletal muscle beta-adrenergic receptors coupled to adenylate cyclase. [3H]Dihydroalprenolol, a potent beta-adrenergic antagonist, was used to identify the adenylate cyclase-coupled beta-adrenoceptors in isolated membranes of rat skeletal muscle. The receptor sites, as revealed by [3H]dihydroalprenolol binding, were predominantly localized in plasmalemmal fraction. That skeletal muscle fraction may also contain the plasmalemma of other intramuscular cells, especially that of blood vessels. Hence, the [3H]dihydroalprenolol binding observed in that fraction may be due partly to its binding to the plasmalemma of blood vessels. Small but consistent binding was also observed in sarcoplasmic reticulum and mitochondria. The level of [3H]dihydroalprenolol binding in different subcellular fractions closely correlated with the level of adenylate cyclase present in those fractions. The binding of [3H]dihydroalprenolol to plasmalemma exhibited saturation kinetics. The binding was rapid, reaching equilibrium within 5 min, and it was readily dissociable. From the kinetics of binding, association (K1) and dissociation (K2) rate constants of 2.21 . 10(7) M-1 . min-1 and 3.21 . 10(-1) min-1, respectively, were obtained. The dissociation constant (Kd) of 15 mM for [3H]dihydroalprenolol obtained from saturation binding data closely agreed with the Kd derived from the ratio of dissociation and association rate constants (K2/K1). Several beta-adrenergic agents known to be active on intact skeletal muscle also competed for [3H]dihydroalprenolol binding sites in isolated plasmalemma with essentially similar selectivity and stereospecificity. Catecholamines competed for [3H]dihydroalprenolol binding sites with a potency of isoproterenol greater than epinephrine greater than norepinephrine. A similar order of potency was noted for catecholamines in the activation of adenylate cyclase. Effects of catecholamines were stereospecific, (-)-isomers being more potent than (+)-isomers. Phenylephrine, an alpha-adrenergic agonist, showed no effect either on [3H]dihydroalprenolol binding or on adenylate cyclase. Known beta-adrenergic antagonists, propranolol and alprenolol, stereospecifically inhibited the [3H]dihydroalprenolol binding and the isoproterenol-stimulated adenylate cyclase. The Ki values for the antagonists determined from inhibition of [3H]dihydroalprenolol binding agreed closely with the Ki values obtained from the inhibition of adenylate cyclase. The data suggest that the binding of [3H]dihydroalprenolol in skeletal muscle membranes possess the characteristics of a substance binding to the beta-adrenergic receptor."}
{"id": "PMID:226167", "title": "Phosphoprotein phosphatase activity at the outer surface of intact normal and transformed 3T3 fibroblasts.", "content": "Using 32P-labeled phosphocasein or phosphohistones as exogenous substrates it was possible to detect a phosphoprotein phosphatase activity on the outer surface of intact normal and transformed 3T3 fibroblasts. Incubation of monolayers of intact cells in buffered salt solution with the radioactively labeled substrate resulted in the release of alkali-labile 32P counts into the surrounding medium. The reaction was: (a) linear with time (at least up to 20 min); (b) proportional to the cell density; (c) dependent on the temperature and pH of the incubation medium; (d) stimulated by K+; and (e) inhibited by sodium fluoride, inorganic pyrophosphate, zinc chloride and relatively impermeant sulfhydryl reagents. Less than 2% of the externally located phosphoprotein phosphatase activity was detectable in pooled cell-free washings of the intact cell monolayer. Phosphocasein did not cause any detectable leakage of intracellular lactate dehydrogenase or soluble phosphoprotein phosphatase activity into the external medium; incubation of the cells with phosphohistones, on the other hand, resulted in appreciable leakage of both these cytoplasmic activities. Neoplastic transformation was associated with a nearly two-fold decrease in the activity of the surface phosphoprotein phosphatase. Addition of serum to either non-transformed 3T3 or spontaneously transformed 3T6 cells resulted in a rapid and remarkeable drop in the cell surface dephosphorylating activity. Acrylamide gel electrophoresis of the dephosphorylated casein or histone substrate revealed no proteolytic degradation or change in electrophoretic mobility. The intact cells showed no damage upon microscopic examination as a result of exposure to phosphocasein or phosphohistones.", "contents": "Phosphoprotein phosphatase activity at the outer surface of intact normal and transformed 3T3 fibroblasts. Using 32P-labeled phosphocasein or phosphohistones as exogenous substrates it was possible to detect a phosphoprotein phosphatase activity on the outer surface of intact normal and transformed 3T3 fibroblasts. Incubation of monolayers of intact cells in buffered salt solution with the radioactively labeled substrate resulted in the release of alkali-labile 32P counts into the surrounding medium. The reaction was: (a) linear with time (at least up to 20 min); (b) proportional to the cell density; (c) dependent on the temperature and pH of the incubation medium; (d) stimulated by K+; and (e) inhibited by sodium fluoride, inorganic pyrophosphate, zinc chloride and relatively impermeant sulfhydryl reagents. Less than 2% of the externally located phosphoprotein phosphatase activity was detectable in pooled cell-free washings of the intact cell monolayer. Phosphocasein did not cause any detectable leakage of intracellular lactate dehydrogenase or soluble phosphoprotein phosphatase activity into the external medium; incubation of the cells with phosphohistones, on the other hand, resulted in appreciable leakage of both these cytoplasmic activities. Neoplastic transformation was associated with a nearly two-fold decrease in the activity of the surface phosphoprotein phosphatase. Addition of serum to either non-transformed 3T3 or spontaneously transformed 3T6 cells resulted in a rapid and remarkeable drop in the cell surface dephosphorylating activity. Acrylamide gel electrophoresis of the dephosphorylated casein or histone substrate revealed no proteolytic degradation or change in electrophoretic mobility. The intact cells showed no damage upon microscopic examination as a result of exposure to phosphocasein or phosphohistones."}
{"id": "PMID:226168", "title": "Location of rat liver iodothyronine deiodinating enzymes in the endoplasmic reticulum.", "content": "The iodothyronine-deiodinating enzymes (iodothyronine-5- and 5'-deiodinase) of rat liver were found to be located in the parenchymal cells. Differential centrifugation of rat liver homogenate revealed that the deiodinases resided mainly in the microsomal fraction. The subcellular distribution pattern of these enzymes correlated best with glucose-6-phosphatase, a marker enzyme of the endoplasmic reticulum. Plasma membranes, prepared by discontinuous sucrose gradient centrifugation, were found to contain very little deiodinating activity. Analysis of fractions obtained during the course of plasma membrane isolation showed that the deiodinases correlated positively with glucose-6-phosphatase (r larger than or equal to 0.98) and negatively with the plasma membrane marker 5'-nucleotidase (r ranging between -0.88 and -0.97). It is concluded that the iodothyronine-deiodinating enzymes of rat liver are associated with the endoplasmic reticulum.", "contents": "Location of rat liver iodothyronine deiodinating enzymes in the endoplasmic reticulum. The iodothyronine-deiodinating enzymes (iodothyronine-5- and 5'-deiodinase) of rat liver were found to be located in the parenchymal cells. Differential centrifugation of rat liver homogenate revealed that the deiodinases resided mainly in the microsomal fraction. The subcellular distribution pattern of these enzymes correlated best with glucose-6-phosphatase, a marker enzyme of the endoplasmic reticulum. Plasma membranes, prepared by discontinuous sucrose gradient centrifugation, were found to contain very little deiodinating activity. Analysis of fractions obtained during the course of plasma membrane isolation showed that the deiodinases correlated positively with glucose-6-phosphatase (r larger than or equal to 0.98) and negatively with the plasma membrane marker 5'-nucleotidase (r ranging between -0.88 and -0.97). It is concluded that the iodothyronine-deiodinating enzymes of rat liver are associated with the endoplasmic reticulum."}
{"id": "PMID:226169", "title": "Rat liver glycogen metabolism in the perinatal period.", "content": "The correlation between blood glucose levels, the concentration of glycogen, the activities of glycogen synthase and phosphorylase and their respective kinases and phosphatases was examined in liver of rat fetuses between day 18 of gestation and one day after birth. Between day 18 and 21 there is a rapid increase in the concentration of glycogen and in the activity of synthase a and a much slower increase in the activity of phosphorylase a. The activity of the respective kinases increased rapidly during this period and reached maximum on day 21. The activity of synthase phosphatase and phosphorylase phosphatase increased after day 18, to reach a maximum on day 19 and 20, respectively, but decreased again towards day 21. The possibility that the changes in glycogen concentration and enzyme activities were related to an effect of glucose or AMP on the respective phosphatases was considered. It was found that the Km of phosphorylase phosphatase for glucose in the prenatal period was 5--7 mM, as in the adult. Since the level of blood glucose during this period was constant (2.8 mM), an effect of glucose on phosphatase activity seems unlikely. AMP concentration increased between day 18 and 21 from 6--15 nmol/g. In view of the low level of phosphorylase a activity during this period, the increase in AMP concentration is not considered to be important in the regulation of glycogen breakdown at this time. Immediately after birth blood glucose levels dropped to 5 mg/dl. This was accompanied by a rapid decrease in glycogen concentration and in the activity of glycogen synthase and a rise in phosphorylase activity. Blood glucose levels returned to the initial level within 1 h after birth, whereas the changes in glycogen concentration and enzyme activities continued for at least 3 h after birth. On day 22 all parameters examined had reached the level found in adult rat liver. It is suggested that the rapid changes observed immediately after birth are due to an effect of gypoglycemia mediated by hormones and cannot be ascribed to direct effects of metabolites on the enzyme systems involved.", "contents": "Rat liver glycogen metabolism in the perinatal period. The correlation between blood glucose levels, the concentration of glycogen, the activities of glycogen synthase and phosphorylase and their respective kinases and phosphatases was examined in liver of rat fetuses between day 18 of gestation and one day after birth. Between day 18 and 21 there is a rapid increase in the concentration of glycogen and in the activity of synthase a and a much slower increase in the activity of phosphorylase a. The activity of the respective kinases increased rapidly during this period and reached maximum on day 21. The activity of synthase phosphatase and phosphorylase phosphatase increased after day 18, to reach a maximum on day 19 and 20, respectively, but decreased again towards day 21. The possibility that the changes in glycogen concentration and enzyme activities were related to an effect of glucose or AMP on the respective phosphatases was considered. It was found that the Km of phosphorylase phosphatase for glucose in the prenatal period was 5--7 mM, as in the adult. Since the level of blood glucose during this period was constant (2.8 mM), an effect of glucose on phosphatase activity seems unlikely. AMP concentration increased between day 18 and 21 from 6--15 nmol/g. In view of the low level of phosphorylase a activity during this period, the increase in AMP concentration is not considered to be important in the regulation of glycogen breakdown at this time. Immediately after birth blood glucose levels dropped to 5 mg/dl. This was accompanied by a rapid decrease in glycogen concentration and in the activity of glycogen synthase and a rise in phosphorylase activity. Blood glucose levels returned to the initial level within 1 h after birth, whereas the changes in glycogen concentration and enzyme activities continued for at least 3 h after birth. On day 22 all parameters examined had reached the level found in adult rat liver. It is suggested that the rapid changes observed immediately after birth are due to an effect of gypoglycemia mediated by hormones and cannot be ascribed to direct effects of metabolites on the enzyme systems involved."}
{"id": "PMID:226170", "title": "Adenosine-induced cyclic AMP increase in pig lymphocytes is not related to adenylate cyclase stimulation.", "content": "Adenosine-cyclic AMP relationships have been studied in pig mesenteric lymph node lymphocytes. The early 2--3-fold increase in cyclic AMP accumulation elicited by adenosine and 2-chloroadenosine, an adenosine deaminase-resistant analogue, could not be correlated to similar effects on the adenylate cyclase activity of disrupted cell preparations, but rather to the competitive inhibition of the low Km (0.17 muM) cyclic AMP phosphodiesterase. The existence of adenosine receptors coupled to lymphocyte adenylate cyclase, which had been proposed by several authors, could not be confirmed by this study Adenosine-cyclic AMP relationships do not appear to be involved in concanavalin A stimulation of pig lymphocytes.", "contents": "Adenosine-induced cyclic AMP increase in pig lymphocytes is not related to adenylate cyclase stimulation. Adenosine-cyclic AMP relationships have been studied in pig mesenteric lymph node lymphocytes. The early 2--3-fold increase in cyclic AMP accumulation elicited by adenosine and 2-chloroadenosine, an adenosine deaminase-resistant analogue, could not be correlated to similar effects on the adenylate cyclase activity of disrupted cell preparations, but rather to the competitive inhibition of the low Km (0.17 muM) cyclic AMP phosphodiesterase. The existence of adenosine receptors coupled to lymphocyte adenylate cyclase, which had been proposed by several authors, could not be confirmed by this study Adenosine-cyclic AMP relationships do not appear to be involved in concanavalin A stimulation of pig lymphocytes."}
{"id": "PMID:226171", "title": "Relationship of prolactin receptors to concanavalin A binding.", "content": "Concanavalin A, which binds to specific carbohydrate determinants on the cell surface, was used to investigate the binding of prolactin to its receptors in liver membranes from female rats. The binding of 125I-labeled ovine prolactin to receptors was sharply inhibited by concanavalin A. This effect was reversed by the competitive sugar alpha-methyl-D-mannopyranoside and thus required the presence of specifically bound lectin. Concentrations of concanavalin A of up to 50 mu/ml caused a progressive decrease in the apparent affinity of the prolactin receptor for hormone. When higher concentrations were used, the number of available binding sites decreased. Concanavalin A-resistant receptors, about 30% of the total, had the same dissociation constant (Kd) as the controls. The binding of 125I-labeled concanavalin A in the same membrane preparations showed the presence of two distinct types of concanavalin A binding. At low concentrations, the lectin bound with high affinity (Kd approximately equal to 6.6 . 10(-8) M. At high lectin concentrations, low affinity (Kd approximately equal to 6.7 . 10(-5) M) binding predominated. Since high affinity concanavalin A binding was saturated at 50 microgram/ml, this class of binding most likely alters the affinity of the prolactin receptor for hormone; low affinity concanavalin A binding may mask prolactin receptors, making them inaccessible to the hormone. Binding sites for concanavalin A and prolactin appear to be independent but closely related since (i) concanavalin A did not displace bound prolactin from its receptor, and (ii) detergent-solubilized 125I-labeled prolactin-receptor complexes bound to concanavalin A-Sepharose and were eluted by alpha-methyl-D-mannopyranoside.", "contents": "Relationship of prolactin receptors to concanavalin A binding. Concanavalin A, which binds to specific carbohydrate determinants on the cell surface, was used to investigate the binding of prolactin to its receptors in liver membranes from female rats. The binding of 125I-labeled ovine prolactin to receptors was sharply inhibited by concanavalin A. This effect was reversed by the competitive sugar alpha-methyl-D-mannopyranoside and thus required the presence of specifically bound lectin. Concentrations of concanavalin A of up to 50 mu/ml caused a progressive decrease in the apparent affinity of the prolactin receptor for hormone. When higher concentrations were used, the number of available binding sites decreased. Concanavalin A-resistant receptors, about 30% of the total, had the same dissociation constant (Kd) as the controls. The binding of 125I-labeled concanavalin A in the same membrane preparations showed the presence of two distinct types of concanavalin A binding. At low concentrations, the lectin bound with high affinity (Kd approximately equal to 6.6 . 10(-8) M. At high lectin concentrations, low affinity (Kd approximately equal to 6.7 . 10(-5) M) binding predominated. Since high affinity concanavalin A binding was saturated at 50 microgram/ml, this class of binding most likely alters the affinity of the prolactin receptor for hormone; low affinity concanavalin A binding may mask prolactin receptors, making them inaccessible to the hormone. Binding sites for concanavalin A and prolactin appear to be independent but closely related since (i) concanavalin A did not displace bound prolactin from its receptor, and (ii) detergent-solubilized 125I-labeled prolactin-receptor complexes bound to concanavalin A-Sepharose and were eluted by alpha-methyl-D-mannopyranoside."}
{"id": "PMID:226172", "title": "[Study of sarcoplasmic reticulum Ca-ATPase by the paramagnetic label--paramagnetic probe method].", "content": "ESR spectra of nitroxyl derivative labelling with parachlormercury benzoate bound with SH-groups of Ca, Mg-dependent ATPase in the presence of Mn2+ ions are studied. It has been concluded from the saturation curves of ESR spectra that Mn2+ is localized at the distance approximately 40 A from the SH-group of the enzyme active centre. Platinum compound (K2PtCl4) changes the spectrum of ESR 1 due to the displacement of the label from the enzyme SH-groups and disintegration of the sarcoplasmic reticulum structure. Palladium compound (Pd(NH3)4Cl2) produced no effect on the ESR 1 spectrum.", "contents": "[Study of sarcoplasmic reticulum Ca-ATPase by the paramagnetic label--paramagnetic probe method]. ESR spectra of nitroxyl derivative labelling with parachlormercury benzoate bound with SH-groups of Ca, Mg-dependent ATPase in the presence of Mn2+ ions are studied. It has been concluded from the saturation curves of ESR spectra that Mn2+ is localized at the distance approximately 40 A from the SH-group of the enzyme active centre. Platinum compound (K2PtCl4) changes the spectrum of ESR 1 due to the displacement of the label from the enzyme SH-groups and disintegration of the sarcoplasmic reticulum structure. Palladium compound (Pd(NH3)4Cl2) produced no effect on the ESR 1 spectrum."}
{"id": "PMID:226173", "title": "[Establishment of the site of electron transport chain disruption in mutant Chlamydomonas chloroplasts with an inactive photosystem 2].", "content": "It has been shown in the studies of 6 strains of non-synthesizing Chlamydomonas reinhardi mutants with a damaged electron-transport chain (ETC) in the region of the Photosystem 2 (PS 2) that the damage is localized on the oxidizing side of PS 2. The ESR studies of the mutants have shown that signal 2 is absent in all the mutants, the width of signal 1 in some mutants is lower than in the control, which is, probably, concerned with the differences in the reaction centre structures. The ETC region from electron inlet from the donor--diphenylcarbaside to P700 is capable of functioning. It is suggested that in all the mutants studied the complex responsible for photodissociation of water is damaged.", "contents": "[Establishment of the site of electron transport chain disruption in mutant Chlamydomonas chloroplasts with an inactive photosystem 2]. It has been shown in the studies of 6 strains of non-synthesizing Chlamydomonas reinhardi mutants with a damaged electron-transport chain (ETC) in the region of the Photosystem 2 (PS 2) that the damage is localized on the oxidizing side of PS 2. The ESR studies of the mutants have shown that signal 2 is absent in all the mutants, the width of signal 1 in some mutants is lower than in the control, which is, probably, concerned with the differences in the reaction centre structures. The ETC region from electron inlet from the donor--diphenylcarbaside to P700 is capable of functioning. It is suggested that in all the mutants studied the complex responsible for photodissociation of water is damaged."}
{"id": "PMID:226178", "title": "New trends in cryoenzymology : II. - Aqueous solutions of enzymes in apolar solvents.", "content": "In order to set up new procedures to investigate enzyme systems at subzero temperatures in pure aqueous media, we used micromicellar solutions which are homogeneous, optically transparent and of low viscosity in that range of temperatures. The preparation and the main properties of such solutions are described along with the behavior of enzyme-substrate intermediates. A critical discussion of results permits to examine advantages as well as limitations of this very promising procedure.", "contents": "New trends in cryoenzymology : II. - Aqueous solutions of enzymes in apolar solvents. In order to set up new procedures to investigate enzyme systems at subzero temperatures in pure aqueous media, we used micromicellar solutions which are homogeneous, optically transparent and of low viscosity in that range of temperatures. The preparation and the main properties of such solutions are described along with the behavior of enzyme-substrate intermediates. A critical discussion of results permits to examine advantages as well as limitations of this very promising procedure."}
{"id": "PMID:226179", "title": "Combined dynamics of EEG and evoked potentials. I. Studies of simultaneously recorded EEG-EPograms in the auditory pathway, reticular formation, and hippocampus of the cat brain during the waking stage.", "content": "This study is carried out on single (not averaged) recordings combining the spontaneous activity preceding the stimulus onset and the EP recorded upon acoustical stimulation. These recordings, which we call EEG-EPograms, are measured simultaneously from different subdural brain structures, such as the auditory cortex, medial geniculate nucleus, inferior colliculus, reticular formation and the hippocampus of awake cats. Using a combined analysis procedure (C.A.P.), the relevant frequency components of spontaneous EEG and EPs, recorded simultaneously from these brain nuclei, are analyzed according to the consistent selectivity bands depicted by the determined amplitude-frequency characteristics. These analyses provide us the following information: (1) there is an important congruency in the time courses of simultaneous response components in common frequency bands, especially in the alpha and beta frequency ranges; (2) there exist significant coupling and synchrony between the evoked amplitude enhancements in the simultaneously recorded single response components; (3) the inter-nuclei coherency in the brain's electrical activity is enormously increased upon stimulation; (4) the evoked response magnitude can be predicted, with reasonable accuracy, from the spontaneous activity preceding the stimulation. The strong dependence of the response magnitude on the stimulus-preceding EEG is explained by means of a model network consisting of a population of relaxation oscillators, which can be brought to different states of synchrony and asynchrony. Some suggestions and comments are also made for investigators working toward theories of signal transmission in the brain.", "contents": "Combined dynamics of EEG and evoked potentials. I. Studies of simultaneously recorded EEG-EPograms in the auditory pathway, reticular formation, and hippocampus of the cat brain during the waking stage. This study is carried out on single (not averaged) recordings combining the spontaneous activity preceding the stimulus onset and the EP recorded upon acoustical stimulation. These recordings, which we call EEG-EPograms, are measured simultaneously from different subdural brain structures, such as the auditory cortex, medial geniculate nucleus, inferior colliculus, reticular formation and the hippocampus of awake cats. Using a combined analysis procedure (C.A.P.), the relevant frequency components of spontaneous EEG and EPs, recorded simultaneously from these brain nuclei, are analyzed according to the consistent selectivity bands depicted by the determined amplitude-frequency characteristics. These analyses provide us the following information: (1) there is an important congruency in the time courses of simultaneous response components in common frequency bands, especially in the alpha and beta frequency ranges; (2) there exist significant coupling and synchrony between the evoked amplitude enhancements in the simultaneously recorded single response components; (3) the inter-nuclei coherency in the brain's electrical activity is enormously increased upon stimulation; (4) the evoked response magnitude can be predicted, with reasonable accuracy, from the spontaneous activity preceding the stimulation. The strong dependence of the response magnitude on the stimulus-preceding EEG is explained by means of a model network consisting of a population of relaxation oscillators, which can be brought to different states of synchrony and asynchrony. Some suggestions and comments are also made for investigators working toward theories of signal transmission in the brain."}
{"id": "PMID:226180", "title": "Pattern separability in a random neural net with inhibitory connections.", "content": "Some interesting properties on pattern separation have been shown through researches by neural models of cerebellar cortex. It seems to us that those results are a part of the properties of pattern separation. A two layer random nerve net with inhibitory connections is given as a model of the cerebellar cortex. The model is composed of threshold elements there. A more general theory of pattern separation than those studied earlier is given, and the pattern separability of the model is considered. It is revealed that the standard deviation of threshold values of threshold elements has a great effect on the pattern separability and the control of the firing rate. The present study is also intended to investigate the pattern separability in such a case that the firing rate of input patterns are not equal, and a pattern includes the other pattern. It is assumed there that the standard deviation is small. Some properties of the degree of pattern separation are cleaned up.", "contents": "Pattern separability in a random neural net with inhibitory connections. Some interesting properties on pattern separation have been shown through researches by neural models of cerebellar cortex. It seems to us that those results are a part of the properties of pattern separation. A two layer random nerve net with inhibitory connections is given as a model of the cerebellar cortex. The model is composed of threshold elements there. A more general theory of pattern separation than those studied earlier is given, and the pattern separability of the model is considered. It is revealed that the standard deviation of threshold values of threshold elements has a great effect on the pattern separability and the control of the firing rate. The present study is also intended to investigate the pattern separability in such a case that the firing rate of input patterns are not equal, and a pattern includes the other pattern. It is assumed there that the standard deviation is small. Some properties of the degree of pattern separation are cleaned up."}
{"id": "PMID:226181", "title": "Information transmission in multi-input-output stochastic neuron models.", "content": "The Shannon's information theory in multi-way channels (Shannon, 1961) is applied to multi-input-output relations of the stochastic automaton models for interaction of excitatory and inhibitory impulse sequences proposed in the previous papers (Tsukada et al., 1977). In these models, the output spike train depends upon several statistical characteristics (mean frequency, standard deviation, form, order-dependence or order-independence, etc.) of the excitatory and inhibitory input spike trains. By the use of the multiple-access channel in information theory, some stochastic properties of temporal pattern discrimination in neurons are analyzed and discussed with biological systems.", "contents": "Information transmission in multi-input-output stochastic neuron models. The Shannon's information theory in multi-way channels (Shannon, 1961) is applied to multi-input-output relations of the stochastic automaton models for interaction of excitatory and inhibitory impulse sequences proposed in the previous papers (Tsukada et al., 1977). In these models, the output spike train depends upon several statistical characteristics (mean frequency, standard deviation, form, order-dependence or order-independence, etc.) of the excitatory and inhibitory input spike trains. By the use of the multiple-access channel in information theory, some stochastic properties of temporal pattern discrimination in neurons are analyzed and discussed with biological systems."}
{"id": "PMID:226177", "title": "[Lipids as possible proton carriers from the respiratory chain to ATP-synthetase and the mechanism of oxidative phosphorylation].", "content": "A scheme of oxidative phosphorylation is suggested according to which at the first stage due to the functioning of the electron-transport chain (ETC) in the points of coupling during relaxation of protein non-equilibrium conformation thermodynamically unfavourable transfer of H+ from H2O into the membrane takes place. Athe 2nd stage H+memb is carried by lipids from ETC-protein to ATP-synthetase. At the 3rd stage ATPase with ATP already contained in the active center seizes 2H+. In the course of subsequent protein relaxation the ATP interaction with the active center is disturbed, and ATP with protons transfers to H2O. In terms of the scheme proposed it proves possible to explain the respiratory control and formation of transmembrane potential difference, as well as the action mechanism of uncouplers and inhibitors of oxidative phosphorylation.", "contents": "[Lipids as possible proton carriers from the respiratory chain to ATP-synthetase and the mechanism of oxidative phosphorylation]. A scheme of oxidative phosphorylation is suggested according to which at the first stage due to the functioning of the electron-transport chain (ETC) in the points of coupling during relaxation of protein non-equilibrium conformation thermodynamically unfavourable transfer of H+ from H2O into the membrane takes place. Athe 2nd stage H+memb is carried by lipids from ETC-protein to ATP-synthetase. At the 3rd stage ATPase with ATP already contained in the active center seizes 2H+. In the course of subsequent protein relaxation the ATP interaction with the active center is disturbed, and ATP with protons transfers to H2O. In terms of the scheme proposed it proves possible to explain the respiratory control and formation of transmembrane potential difference, as well as the action mechanism of uncouplers and inhibitors of oxidative phosphorylation."}
{"id": "PMID:226182", "title": "Analysis of \"integrate-to-threshold\" neural coding schemes.", "content": "Methods of analysis for some deterministic and stochastic variants of the integrate-to-threshold neural coding scheme are presented. Adaptation phenomena are modeled by means of feedforward and feedback adaptive threshold control. Simulations of sinusoidal and step responses reproduce satisfactorily the qualitative characteristics of adaptation as compared with physiological data. It is postulated that such adaptive threshold control may be accomplished by the release, or conformation change, of molecules involved in the control of excitable-channel dynamics.", "contents": "Analysis of \"integrate-to-threshold\" neural coding schemes. Methods of analysis for some deterministic and stochastic variants of the integrate-to-threshold neural coding scheme are presented. Adaptation phenomena are modeled by means of feedforward and feedback adaptive threshold control. Simulations of sinusoidal and step responses reproduce satisfactorily the qualitative characteristics of adaptation as compared with physiological data. It is postulated that such adaptive threshold control may be accomplished by the release, or conformation change, of molecules involved in the control of excitable-channel dynamics."}
{"id": "PMID:226183", "title": "Synergism and antagonism of neurons caused by an electrical synapse.", "content": "To investigate the role of electrical junction, a model system consisting of two electrically coupled neurons was studied. It was revealed that the model system generates both the in-phase pattern and the anti-phase pattern stably. Physiological condierations revealed the following. The in-phase discharge pattern (synergism) is a unique output of a electrically coupled pacemaker neurons. However, both the in-phase (synergism) and the anti-phase (antagonism) discharge patterns are possible for electrically coupled bursting neurons. We may expect other discharge patterns, such as a random discharge pattern (chaos), than the inphase and the anti-phase pattern in electrically coupled neurons. Random firing patterns in the inferior olive may be attributed to electrical synapses. Until now, we have assumed that excitation periods of two neurons were almost the same. When two periods are greatly different, various phenomena are expected. Determination of the stability of the anti-phase solution by the analytical methods, when diffusion constants are very small, is one of our future problems.", "contents": "Synergism and antagonism of neurons caused by an electrical synapse. To investigate the role of electrical junction, a model system consisting of two electrically coupled neurons was studied. It was revealed that the model system generates both the in-phase pattern and the anti-phase pattern stably. Physiological condierations revealed the following. The in-phase discharge pattern (synergism) is a unique output of a electrically coupled pacemaker neurons. However, both the in-phase (synergism) and the anti-phase (antagonism) discharge patterns are possible for electrically coupled bursting neurons. We may expect other discharge patterns, such as a random discharge pattern (chaos), than the inphase and the anti-phase pattern in electrically coupled neurons. Random firing patterns in the inferior olive may be attributed to electrical synapses. Until now, we have assumed that excitation periods of two neurons were almost the same. When two periods are greatly different, various phenomena are expected. Determination of the stability of the anti-phase solution by the analytical methods, when diffusion constants are very small, is one of our future problems."}
{"id": "PMID:226185", "title": "Plasma renin activity and adrenal angiotensin II receptors in fetal, newborn, adult and pregnant rabbits.", "content": "Plasma renin activity (PRA) and adrenal angiotensin II receptors have been studied simultaneously in the rabbit at various stages of development. In the fetus both parameters show very low values but increase rapidly during the last 4 days of gestation. PRA reaches a maximal level in the early post-natal period but the concentration of adrenal angiotensin II receptors continues to increase further up to the adult state. In adult females, pregnancy results in an initial rise in PRA and adrenocortical angiotensin II receptors. However, PRA remains at a high level throughout the gestation period whereas the number of adrenocortical angiotensin II receptors decreases progressively as pregnancy progresses. The role of circulating angiotensin in the regulation of the concentration and affinity of its receptor sites is discussed.", "contents": "Plasma renin activity and adrenal angiotensin II receptors in fetal, newborn, adult and pregnant rabbits. Plasma renin activity (PRA) and adrenal angiotensin II receptors have been studied simultaneously in the rabbit at various stages of development. In the fetus both parameters show very low values but increase rapidly during the last 4 days of gestation. PRA reaches a maximal level in the early post-natal period but the concentration of adrenal angiotensin II receptors continues to increase further up to the adult state. In adult females, pregnancy results in an initial rise in PRA and adrenocortical angiotensin II receptors. However, PRA remains at a high level throughout the gestation period whereas the number of adrenocortical angiotensin II receptors decreases progressively as pregnancy progresses. The role of circulating angiotensin in the regulation of the concentration and affinity of its receptor sites is discussed."}
{"id": "PMID:226186", "title": "Effect of cyclic nucleotides on weight of gastrocnemius and creatine kinase activity after denervation of muscle in young rats.", "content": "Denervation of the gastrocnemius muscle at various stages of development reduces muscle weight and creatine kinase activity. An inverse relationship between the muscle-specific enzyme, creatine kinase, and the lysosomal enzyme, acid phosphatase, was shown. An increased percentage of the BB isoenzyme of creatine kinase is observed after long-term denervation. Apparently the muscle tissue has the ability to regenerate and presumptive myoblasts are formed from satellite cells. When the denervated muscle is treated with dibutyryl-cyclic-GMP administration new muscle tissue has been formed. Similar effects could not be demonstrated with either cyclic AMP or succinylcholine. The higher percentage of the BB isoenzyme after dibutyryl-cyclic-GMP administration supports the theory that presumptive myoblasts are derived from satellite cells. Succinylcholine also causes an increase of the B-type of creatine kinase. It can be concluded that cyclic GMP, generated via the nerve, has an important role in maintaining muscle weight.", "contents": "Effect of cyclic nucleotides on weight of gastrocnemius and creatine kinase activity after denervation of muscle in young rats. Denervation of the gastrocnemius muscle at various stages of development reduces muscle weight and creatine kinase activity. An inverse relationship between the muscle-specific enzyme, creatine kinase, and the lysosomal enzyme, acid phosphatase, was shown. An increased percentage of the BB isoenzyme of creatine kinase is observed after long-term denervation. Apparently the muscle tissue has the ability to regenerate and presumptive myoblasts are formed from satellite cells. When the denervated muscle is treated with dibutyryl-cyclic-GMP administration new muscle tissue has been formed. Similar effects could not be demonstrated with either cyclic AMP or succinylcholine. The higher percentage of the BB isoenzyme after dibutyryl-cyclic-GMP administration supports the theory that presumptive myoblasts are derived from satellite cells. Succinylcholine also causes an increase of the B-type of creatine kinase. It can be concluded that cyclic GMP, generated via the nerve, has an important role in maintaining muscle weight."}
{"id": "PMID:226187", "title": "Bimodal distribution of REM sleep latencies in depression.", "content": "The REM sleep latency of endogenously depressed patients was investigated by analyzing 90 polysomnograms of six patients during depression and 58 polysomnograms of four of these patients after remission. During depression the REM sleep latencies are distributed bimodally with peaks at sleep onset (sleep onset REM phases, SOREMPs) and 60 min later. During the follow-up examinations some time after remission, the occurrence of SOREMPs is very rare. A model is proposed according to which the occurrence of SOREMPs in the sleep of these patients is caused by a reduced amplitude of the circadian rhythm of the arousal system.", "contents": "Bimodal distribution of REM sleep latencies in depression. The REM sleep latency of endogenously depressed patients was investigated by analyzing 90 polysomnograms of six patients during depression and 58 polysomnograms of four of these patients after remission. During depression the REM sleep latencies are distributed bimodally with peaks at sleep onset (sleep onset REM phases, SOREMPs) and 60 min later. During the follow-up examinations some time after remission, the occurrence of SOREMPs is very rare. A model is proposed according to which the occurrence of SOREMPs in the sleep of these patients is caused by a reduced amplitude of the circadian rhythm of the arousal system."}
{"id": "PMID:226193", "title": "Surface chemistry and cytotoxic properties of silica.", "content": "Aluminium inhibits the harmful effect of quartz on the lungs. Current interest in such protective phenomena has lead us to consider a possible method of bonding aluminium to the crystal lattice, and to see if other atoms might have the same effect. A study of the structure of natural and artificial alumino-silicic compounds shows a surface state specific to quartz, namely the existence of vacancies in the three-dimensional SiO4 tetrahedral structure. Aluminium is a known inhibitor of the cytotoxic action of quartz, and can replace the missing silicon atoms in the crystal lattice. The result is the generation of finite numbers of heat-resistant acid sites. Thus it is not a question of a simple zeolite surface layer, but of the substitution of aluminium atoms for silicon atoms in the remaining crystal lattice. It can be shown that other atoms, such as sulphur and specially phosphorus, are capable of behaving in the same way as aluminium. There is reason to believe that the cytotoxic properties of quartz may be related to the crystal capturing atoms from the cell membrane. The large number of thermally stable acid sites detected after contact with alumina would then be a factor for assessing the cytotoxic properties of the various forms of quartz.", "contents": "Surface chemistry and cytotoxic properties of silica. Aluminium inhibits the harmful effect of quartz on the lungs. Current interest in such protective phenomena has lead us to consider a possible method of bonding aluminium to the crystal lattice, and to see if other atoms might have the same effect. A study of the structure of natural and artificial alumino-silicic compounds shows a surface state specific to quartz, namely the existence of vacancies in the three-dimensional SiO4 tetrahedral structure. Aluminium is a known inhibitor of the cytotoxic action of quartz, and can replace the missing silicon atoms in the crystal lattice. The result is the generation of finite numbers of heat-resistant acid sites. Thus it is not a question of a simple zeolite surface layer, but of the substitution of aluminium atoms for silicon atoms in the remaining crystal lattice. It can be shown that other atoms, such as sulphur and specially phosphorus, are capable of behaving in the same way as aluminium. There is reason to believe that the cytotoxic properties of quartz may be related to the crystal capturing atoms from the cell membrane. The large number of thermally stable acid sites detected after contact with alumina would then be a factor for assessing the cytotoxic properties of the various forms of quartz."}
{"id": "PMID:226194", "title": "Diagnosis of Niemann-Pick disease by analysis of hair-roots.", "content": "A micromethod for the measurement of sphingomyelinase in hair root lysates was described. With this method, 22 normal individuals, 3 children affected with Niemann-Pick disease and 2 carriers have been studied. It seems clear that Niemann-Pick homozygotes can be diagnosed definitively, but more extensive studies arenecessary to decide if carrier detection with hair-roots is possible. The particular interest of using hair roots is that the material can be sampled easily and mailed without special precautions.", "contents": "Diagnosis of Niemann-Pick disease by analysis of hair-roots. A micromethod for the measurement of sphingomyelinase in hair root lysates was described. With this method, 22 normal individuals, 3 children affected with Niemann-Pick disease and 2 carriers have been studied. It seems clear that Niemann-Pick homozygotes can be diagnosed definitively, but more extensive studies arenecessary to decide if carrier detection with hair-roots is possible. The particular interest of using hair roots is that the material can be sampled easily and mailed without special precautions."}
{"id": "PMID:226195", "title": "Specific passive immunotherapy of experimental lymphoma. Effects of macrophage toxic drugs.", "content": "Sub-lethal irradiation experiments have indicated that undamaged host cells are necessary for efficiency of specific passive tumour immunotherapy. To further indentify these host cells, the effect of known macrophage toxic agents (silica, carrageenan, trypan blue) were tested on passive immunotherapy of a Gross virus induced C57BL/6 mouse lymphoma with specific W/Fu rat anti-Gross cell surface antigens serum. Median survival time of serum treated mice was significantly decreased when toxic drug was injected three hours before tumour cell injection and seven hours before the beginning of passive immunotherapy, only if silica (5 mg i.p./mouse) or carrageenan (2.5 mg i.p./mouse) but not if trypan blue (4 mg i.p./mouse) was used. Pretreatment by PVNO, a macrophage protecting agent, 24 hours before, inhibited silica effect but not carrageenan effect on the passive immunotherapy. These results indicate that host's phagocytic cells are likely to be involved in the efficiency of passive antibody mediated tumour cell destruction, possibly through opsonization. However, more than one phagocyte population may participate in such a mechanism.", "contents": "Specific passive immunotherapy of experimental lymphoma. Effects of macrophage toxic drugs. Sub-lethal irradiation experiments have indicated that undamaged host cells are necessary for efficiency of specific passive tumour immunotherapy. To further indentify these host cells, the effect of known macrophage toxic agents (silica, carrageenan, trypan blue) were tested on passive immunotherapy of a Gross virus induced C57BL/6 mouse lymphoma with specific W/Fu rat anti-Gross cell surface antigens serum. Median survival time of serum treated mice was significantly decreased when toxic drug was injected three hours before tumour cell injection and seven hours before the beginning of passive immunotherapy, only if silica (5 mg i.p./mouse) or carrageenan (2.5 mg i.p./mouse) but not if trypan blue (4 mg i.p./mouse) was used. Pretreatment by PVNO, a macrophage protecting agent, 24 hours before, inhibited silica effect but not carrageenan effect on the passive immunotherapy. These results indicate that host's phagocytic cells are likely to be involved in the efficiency of passive antibody mediated tumour cell destruction, possibly through opsonization. However, more than one phagocyte population may participate in such a mechanism."}
{"id": "PMID:226196", "title": "The growth-hormone in long-term steroid-treated patients with chronic active hepatitis.", "content": "To determine whether the hypothalamo-pituitary axis (HPA) became suppressed in patients with chronic active hepatitis (CAH) treated with prednisone or long-activity synthetic corticotrophin (L.A.S.C.) for at least 12 months 36 patients with CAH were assessed for growth hormone release following insulin hypoglycemia test (IHT). Sixteen out of the 36 patients were treated with steroids, 11 with L.A.S.C. and 9 were untreated. Sixteen patients were less than 12 years old of whom 8 were treated with prednisone and 5 with L.A.S.C. and 3 untreated. Suppression of HPA was observed only in two patients of whom one was treated with prednisolone for 24 months and the other one received L.A.S.C. for 23 months. Normal HPA was observed in all the other 34 patients. Two patients aged 6 and 8 years were treated with steroids for 3 and 6 years respectively and showed impairment of the growth in height and remained permanently stunted even when steroids had been discontinued. Our data suggest that both steroids and L.A.S.C. treatment does not impair HPA in patients with CAH when administered for less than two years.", "contents": "The growth-hormone in long-term steroid-treated patients with chronic active hepatitis. To determine whether the hypothalamo-pituitary axis (HPA) became suppressed in patients with chronic active hepatitis (CAH) treated with prednisone or long-activity synthetic corticotrophin (L.A.S.C.) for at least 12 months 36 patients with CAH were assessed for growth hormone release following insulin hypoglycemia test (IHT). Sixteen out of the 36 patients were treated with steroids, 11 with L.A.S.C. and 9 were untreated. Sixteen patients were less than 12 years old of whom 8 were treated with prednisone and 5 with L.A.S.C. and 3 untreated. Suppression of HPA was observed only in two patients of whom one was treated with prednisolone for 24 months and the other one received L.A.S.C. for 23 months. Normal HPA was observed in all the other 34 patients. Two patients aged 6 and 8 years were treated with steroids for 3 and 6 years respectively and showed impairment of the growth in height and remained permanently stunted even when steroids had been discontinued. Our data suggest that both steroids and L.A.S.C. treatment does not impair HPA in patients with CAH when administered for less than two years."}
{"id": "PMID:226197", "title": "Infantile gastroenteritis caused by rotavirus: comparison of enzyme-linked immunosorbent assay and electron microscopy for rapid diagnosis.", "content": "ELISA and negative contrast EM have used for the detection of rotavirus in one hundred stools from children, less than two years old, hospitalized for acute gastro-enteritis during the winter 1977-78. Samples obtained from the same children some months after hospitalization were also tested. A good correlation was found between the results given by EM and ELISA, but the later technique turned out to be more sensitive (12% more positive using ELISA). A rotavirus infection could be demonstrated in 73% of the patients. In the stools of 3 children we found a second virus in association with the rotavirus, and in two cases a pathogenic bacterium. When a second serum specimen was available from children previously infected by rotavirus it was always possible to detect a significant increase in CF antibodies. Several months after hospitalization a 2nd survey indicated that the rotavirus was no longer present but calicivirus, echovirus, coxsackievirus and adenovirus could be detected in those asymptomatic children.", "contents": "Infantile gastroenteritis caused by rotavirus: comparison of enzyme-linked immunosorbent assay and electron microscopy for rapid diagnosis. ELISA and negative contrast EM have used for the detection of rotavirus in one hundred stools from children, less than two years old, hospitalized for acute gastro-enteritis during the winter 1977-78. Samples obtained from the same children some months after hospitalization were also tested. A good correlation was found between the results given by EM and ELISA, but the later technique turned out to be more sensitive (12% more positive using ELISA). A rotavirus infection could be demonstrated in 73% of the patients. In the stools of 3 children we found a second virus in association with the rotavirus, and in two cases a pathogenic bacterium. When a second serum specimen was available from children previously infected by rotavirus it was always possible to detect a significant increase in CF antibodies. Several months after hospitalization a 2nd survey indicated that the rotavirus was no longer present but calicivirus, echovirus, coxsackievirus and adenovirus could be detected in those asymptomatic children."}
{"id": "PMID:226198", "title": "Cholesterol synthesis by human fibroblasts in the presence of LDL and anti-LDL IgA.", "content": "LDL interact with fibroblasts through specific membrane sites. This reaction is the first step of a mechanism which leads to the regulation of intracellular cholesterol synthesis. When LDL form a complex with an IgA from a myeloma serum with mixed hyperlipidemia and xanthomatosis, they no longer function as a regulator, and the result is excess production of free intracellular cholesterol. No excess cholesterol production is observed when myeloma IgA is replaced by control IgG and IgA.", "contents": "Cholesterol synthesis by human fibroblasts in the presence of LDL and anti-LDL IgA. LDL interact with fibroblasts through specific membrane sites. This reaction is the first step of a mechanism which leads to the regulation of intracellular cholesterol synthesis. When LDL form a complex with an IgA from a myeloma serum with mixed hyperlipidemia and xanthomatosis, they no longer function as a regulator, and the result is excess production of free intracellular cholesterol. No excess cholesterol production is observed when myeloma IgA is replaced by control IgG and IgA."}
{"id": "PMID:226199", "title": "Thermodynamic compensation process in interacting protein systems: definition of thermodynamic compensatory temperature, (Tc).", "content": "In our thermodynamic analysis of the non-linear Van't Hoff expression as applied to several self-associating systems -- specifically in the cases of bovine liver L-glutamate dehydrogenase (GDH), glucagon and S-carboxymethylated apo A-II protein from human high density lipoprotein -- we have examined the interrelationships of a number of thermodynamic temperatures as they affect the association process. We found the principal determinants of the linear thermodynamic compensation process to be delta S0(T)/delta C0p(T) = (delta T'C)/(Texp), where (delta T'C) = Texp). We have defined the unique compensatory temperature, (TC), for any interacting system, at which the contributions of enthalpy and entropy to the association process are balanced.", "contents": "Thermodynamic compensation process in interacting protein systems: definition of thermodynamic compensatory temperature, (Tc). In our thermodynamic analysis of the non-linear Van't Hoff expression as applied to several self-associating systems -- specifically in the cases of bovine liver L-glutamate dehydrogenase (GDH), glucagon and S-carboxymethylated apo A-II protein from human high density lipoprotein -- we have examined the interrelationships of a number of thermodynamic temperatures as they affect the association process. We found the principal determinants of the linear thermodynamic compensation process to be delta S0(T)/delta C0p(T) = (delta T'C)/(Texp), where (delta T'C) = Texp). We have defined the unique compensatory temperature, (TC), for any interacting system, at which the contributions of enthalpy and entropy to the association process are balanced."}
{"id": "PMID:226200", "title": "The water proton spin-lattice relaxation times in virus-infected cells.", "content": "The water proton spin-lattice relaxation times in HEp-2 cell cultures were determined immediately after 1 h of polio-virus adsorption. The shortening of the water T1 was closely related to the multiplicity of infection, allowing direct inspections of the virus--cell interaction since the first steps of the infectious cycle. Virus-induced structural and conformational changes of cell constituents were suggested to be detectable by NMR investigation of cell water.", "contents": "The water proton spin-lattice relaxation times in virus-infected cells. The water proton spin-lattice relaxation times in HEp-2 cell cultures were determined immediately after 1 h of polio-virus adsorption. The shortening of the water T1 was closely related to the multiplicity of infection, allowing direct inspections of the virus--cell interaction since the first steps of the infectious cycle. Virus-induced structural and conformational changes of cell constituents were suggested to be detectable by NMR investigation of cell water."}
{"id": "PMID:226201", "title": "Potentiometric method for substrate analysis using immobilized NAD + -dependent oxidoreductase enzymes.", "content": "Two coenzyme-dependent oxidoreductases, glucose dehydrogenase and alcohol dehydrogenase, were immobilized in polyacrylamide gel over a platinum grid matrix and used as enzyme electrodes to measure their substrate concentrations in buffered aqueous solutions. The immobilized enzymes were used to oxidize their substrates in the presence of NAD +. Ferricyanide was used as the redox mediator and electroactive species. The determinations of glucose and ethanol were utilized to demonstrate and evaluate the performance of the system. The described methodology should be readily applicable to the analysis of numerous other substrates of coenzyme-dependent oxidoreductases.", "contents": "Potentiometric method for substrate analysis using immobilized NAD + -dependent oxidoreductase enzymes. Two coenzyme-dependent oxidoreductases, glucose dehydrogenase and alcohol dehydrogenase, were immobilized in polyacrylamide gel over a platinum grid matrix and used as enzyme electrodes to measure their substrate concentrations in buffered aqueous solutions. The immobilized enzymes were used to oxidize their substrates in the presence of NAD +. Ferricyanide was used as the redox mediator and electroactive species. The determinations of glucose and ethanol were utilized to demonstrate and evaluate the performance of the system. The described methodology should be readily applicable to the analysis of numerous other substrates of coenzyme-dependent oxidoreductases."}
{"id": "PMID:226205", "title": "Cholangiocarcinoma.", "content": "Cholangiocarcinoma may arise in the small bile ducts within the liver or in the large ducts in the hilum or the extrahepatic biliary tree. Curative surgical excision is being increasingly attempted for tumours at all sites and the best results are achieved with cancer at the lower end of the common bile duct. Palliative bypass surgery to drain the biliary tree gives good symptomatic relief and may provide prolonged survival because these tumours are often slow growing. Radiotherapy deserves more extensive trials since about 50 per cent of patients derive benefit. The results of treatment with cytotoxic drugs are so far disappointing.", "contents": "Cholangiocarcinoma. Cholangiocarcinoma may arise in the small bile ducts within the liver or in the large ducts in the hilum or the extrahepatic biliary tree. Curative surgical excision is being increasingly attempted for tumours at all sites and the best results are achieved with cancer at the lower end of the common bile duct. Palliative bypass surgery to drain the biliary tree gives good symptomatic relief and may provide prolonged survival because these tumours are often slow growing. Radiotherapy deserves more extensive trials since about 50 per cent of patients derive benefit. The results of treatment with cytotoxic drugs are so far disappointing."}
{"id": "PMID:226206", "title": "Incidence of carcinoma in situ of germ cells in contralateral testis of men with testicular tumours.", "content": "Biopsy specimens from the contralateral testicle in 50 consecutive patients with germinal testicular cancer were examined for carcinoma in situ. Three out of 21 men with seminomas and one out of 29 with other types of germinal cancer (8%) had carcinoma in situ in the contralateral testicle without any clinical signs. One of these men developed early invasive germ-cell cancer 46 months after carcinoma in situ was first diagnosed. The others have been followed up for less than a year without signs of tumour growth. If these results are confirmed routine biopsy of the contralateral testicle in patients with germinal cancer may be indicated.", "contents": "Incidence of carcinoma in situ of germ cells in contralateral testis of men with testicular tumours. Biopsy specimens from the contralateral testicle in 50 consecutive patients with germinal testicular cancer were examined for carcinoma in situ. Three out of 21 men with seminomas and one out of 29 with other types of germinal cancer (8%) had carcinoma in situ in the contralateral testicle without any clinical signs. One of these men developed early invasive germ-cell cancer 46 months after carcinoma in situ was first diagnosed. The others have been followed up for less than a year without signs of tumour growth. If these results are confirmed routine biopsy of the contralateral testicle in patients with germinal cancer may be indicated."}
{"id": "PMID:226208", "title": "Static and dynamic fusimotor interaction and the possibility of multiple pace-makers operating in the cat muscle spindle.", "content": "The interaction of static and dynamic fusimotor activation on the firing of primary muscle spindle afferents has been studied in the cat soleus muscle at constant length and during sinusoidal stretching. Cycle histogram analysis revealed summation of static and dynamic action during the peak of the afferent response to sinusoidal stretching, while static action completely occluded the dynamic effect during the trough of the response. Occlusion was complete as long as, for single fusimotor activation, the static-induced trough response exceeded the dynamic-induced one by about 25%. The investigation of inter-spike interval distributions obtained at constant muscle length revealed occlusion of dynamic by static action in 8 out of 13 cases. A model of multiple spike generation in primary spindle afferents is considered which is based on two or more pacemakers arranged in parallel, with a common pacemaker in series.", "contents": "Static and dynamic fusimotor interaction and the possibility of multiple pace-makers operating in the cat muscle spindle. The interaction of static and dynamic fusimotor activation on the firing of primary muscle spindle afferents has been studied in the cat soleus muscle at constant length and during sinusoidal stretching. Cycle histogram analysis revealed summation of static and dynamic action during the peak of the afferent response to sinusoidal stretching, while static action completely occluded the dynamic effect during the trough of the response. Occlusion was complete as long as, for single fusimotor activation, the static-induced trough response exceeded the dynamic-induced one by about 25%. The investigation of inter-spike interval distributions obtained at constant muscle length revealed occlusion of dynamic by static action in 8 out of 13 cases. A model of multiple spike generation in primary spindle afferents is considered which is based on two or more pacemakers arranged in parallel, with a common pacemaker in series."}
{"id": "PMID:226209", "title": "Pharmacological characterization of GABA receptors mediating vasodilation of verebral arteries in vitro.", "content": "GABA (gamma-aminobutyric acid) produced a dose-dependent dilation of isolated cat and dog cerebral artery segments which had been given an active, tonic contraction by either prostaglandin F2 alpha or serotonin. No effect of GABA on extracranial blood vessels was observed. The GABA-induced dilation could be blocked in a dose-dependent manner by either bicuculline or picrotoxin. The latter agent appeared to act as a competitive antagonist. GABA agonists muscimol, imidazoleacetic acid, delta-aminovaleric acid, (+/-)gamma-amino-beta-hydroxybutyric acid, and beta-alanine also relaxed actively contracted cerebral arteries dose-dependently. The relative potency of these agonists was consistent with that established for GABA receptors on neurons and invertebrate striated muscle. GABA was also tested on two human cerebral arteries and found to cause a small dilation. The results support the existence of a cerebrovascular GABA receptor which may mediate an interaction between GABA and the cerebral circulatory system.", "contents": "Pharmacological characterization of GABA receptors mediating vasodilation of verebral arteries in vitro. GABA (gamma-aminobutyric acid) produced a dose-dependent dilation of isolated cat and dog cerebral artery segments which had been given an active, tonic contraction by either prostaglandin F2 alpha or serotonin. No effect of GABA on extracranial blood vessels was observed. The GABA-induced dilation could be blocked in a dose-dependent manner by either bicuculline or picrotoxin. The latter agent appeared to act as a competitive antagonist. GABA agonists muscimol, imidazoleacetic acid, delta-aminovaleric acid, (+/-)gamma-amino-beta-hydroxybutyric acid, and beta-alanine also relaxed actively contracted cerebral arteries dose-dependently. The relative potency of these agonists was consistent with that established for GABA receptors on neurons and invertebrate striated muscle. GABA was also tested on two human cerebral arteries and found to cause a small dilation. The results support the existence of a cerebrovascular GABA receptor which may mediate an interaction between GABA and the cerebral circulatory system."}
{"id": "PMID:226210", "title": "Two different and compatible intraneuronal labels for ultrastructural study of synaptically related cells.", "content": "To examine the structural interactions between synaptically connected neurons in Aplysia, we have developed a method for simultaneously labeling two identified cell with different and compatible intraneuronal marking agents (horseradish peroxidase and [3H]N-acetyl-D-galactosamine) visible in both the light and electron microscopes. Combining these two agents within a single cell yields a third label.", "contents": "Two different and compatible intraneuronal labels for ultrastructural study of synaptically related cells. To examine the structural interactions between synaptically connected neurons in Aplysia, we have developed a method for simultaneously labeling two identified cell with different and compatible intraneuronal marking agents (horseradish peroxidase and [3H]N-acetyl-D-galactosamine) visible in both the light and electron microscopes. Combining these two agents within a single cell yields a third label."}
{"id": "PMID:226211", "title": "Circulation of cortical spreading depression around electrically stimulated areas and epileptic foci in the neocortex of rats.", "content": "Spreading depression (SD) elicited in the cerebral cortex of anaesthetized rats does not penetrate into epileptic foci (penicillin) or cortical regions subjected to repetitive electrical stimulation (6--10 Hz, 0.05--0.01 msec). The extent of the SD block, monitored by the absence of the slow potential change and preservation of spontaneous and evoked EEG activity, can be varied in certain limits by changing the stimulus parameters. When the diameter of the block in the parietal cortex is reduced at a time when its temporal boundary is circumvented by an SD wave, propagating in the rostral direction, a strip of cortical tissue between the block and sagittal sulcus is opened for SD which spreads through this route from the frontal to the occipital cortex and starts reverberating around the block. Other methods for eliciting SD reverberation employ removal of an additional block in a section of the circular pathway and directionally biased propagation around the stimulation point. SD reverberation lasting for at least 3 cycles was observed 109 times (median number of completed cycles 5.2, average cycle duration 4.4 +/- 0.1 min). It is suggested that SD reverberation around an epileptic focus can account for slow oscillations of ictal and interictal discharge and for recurrent seizures.", "contents": "Circulation of cortical spreading depression around electrically stimulated areas and epileptic foci in the neocortex of rats. Spreading depression (SD) elicited in the cerebral cortex of anaesthetized rats does not penetrate into epileptic foci (penicillin) or cortical regions subjected to repetitive electrical stimulation (6--10 Hz, 0.05--0.01 msec). The extent of the SD block, monitored by the absence of the slow potential change and preservation of spontaneous and evoked EEG activity, can be varied in certain limits by changing the stimulus parameters. When the diameter of the block in the parietal cortex is reduced at a time when its temporal boundary is circumvented by an SD wave, propagating in the rostral direction, a strip of cortical tissue between the block and sagittal sulcus is opened for SD which spreads through this route from the frontal to the occipital cortex and starts reverberating around the block. Other methods for eliciting SD reverberation employ removal of an additional block in a section of the circular pathway and directionally biased propagation around the stimulation point. SD reverberation lasting for at least 3 cycles was observed 109 times (median number of completed cycles 5.2, average cycle duration 4.4 +/- 0.1 min). It is suggested that SD reverberation around an epileptic focus can account for slow oscillations of ictal and interictal discharge and for recurrent seizures."}
{"id": "PMID:226212", "title": "The amplitude of post-tetanic potentiation of the EPSP RC1-R15 in Aplysia is modulated by environmental parameters.", "content": "Evidence is presented that the EPSP called RC1-R15, which is recorded from cell R15 of the abdominal ganglion of Aplysia californica upon appropriate stimulation of the right connective, is endogenously active. In previous studies we showed that after repetitive stimulation the amplitude of this EPSP increases and then slowly decays over many minutes, a phenomenon called post-tetanic potentiation (PTP). The rate of endogenous firing of this EPSP varies with time of day and tonicity of the animal's external environment. It is shown that this endogenous firing increases the magnitude of the PTP component of the amplitude of the EPSP. The degree of this potentiation varies with the endogenous firing rate. In general, daytime or a hypertonic external environment increases the firing rate of the EPSP and its degree of potentiation. Since the degree of this PTP reflects time of day and environmental tonicity, it is inferred that it conveys physiologically significant information to the postsynaptic cell R15.", "contents": "The amplitude of post-tetanic potentiation of the EPSP RC1-R15 in Aplysia is modulated by environmental parameters. Evidence is presented that the EPSP called RC1-R15, which is recorded from cell R15 of the abdominal ganglion of Aplysia californica upon appropriate stimulation of the right connective, is endogenously active. In previous studies we showed that after repetitive stimulation the amplitude of this EPSP increases and then slowly decays over many minutes, a phenomenon called post-tetanic potentiation (PTP). The rate of endogenous firing of this EPSP varies with time of day and tonicity of the animal's external environment. It is shown that this endogenous firing increases the magnitude of the PTP component of the amplitude of the EPSP. The degree of this potentiation varies with the endogenous firing rate. In general, daytime or a hypertonic external environment increases the firing rate of the EPSP and its degree of potentiation. Since the degree of this PTP reflects time of day and environmental tonicity, it is inferred that it conveys physiologically significant information to the postsynaptic cell R15."}
{"id": "PMID:226213", "title": "Neocortical pyramidal cells: a model with dendritic calcium conductance reproduces repetitive firing and epileptic behavior.", "content": "A computer model of a neocortical pyramidal cell has been constructed using ideas similar to those used for hippocampal pyramidal cells. This model has been applied to the study of (a) repetitive firing, and (b) the paroxysmal depolarizing shift (PDS), an important intracellular event during seizures. Although calcium spikes have not been demonstrated directly in neocortical cells, we have postulated (by analogy with hippocampal pyramidal cells) a dendritic calcium conductance and a 'slow potassium' conductance modulated by intracellular calcium ion. With these dendritic ionic conductances, the model is able to reproduce the following experimental features of neocortical pyramidal cells: the afterdepolarization and succeeding afterhyperpolarization after an antidromic spike, and the f-I (firing rate-injected current) curve. Some of the differences between 'fast' and 'slow' pyramidal tract neurons (PTNs) -- narrower spikes and a steeper f-I curve in the fast PTNs -- may be explained by differences in Hodgkin-Huxley potassium kinetics between the two kinds of cell. The same model which faithfully reproduces repetitive firing behavior also reproduces (given appropriate synaptic inputs) the following intracellular events recording during epileptic seizures: (a) a burst of action potentials superimposed on and followed by a PDS, and (b) rapid repetitive firing succeeded by an IPSP. Thus, a single set of parameters can reporduce both normal physiological behavior and 'epileptic' behavior: the particular behavior seen depending on how the cell is stimulated. This overall result is the same as for our model of the CA1 hippocampal cell. It suggests that certain acutely acting epileptogenic agents, e.g. penicillin, may act by increasing synaptic input (perhaps both excitatory and inhibitory) to pyramidal cells, rather than by altering their membrane properties. As in our CA1 hippocampal cell model, bursting seems to be a phenomenon generated by the apical dendrite.", "contents": "Neocortical pyramidal cells: a model with dendritic calcium conductance reproduces repetitive firing and epileptic behavior. A computer model of a neocortical pyramidal cell has been constructed using ideas similar to those used for hippocampal pyramidal cells. This model has been applied to the study of (a) repetitive firing, and (b) the paroxysmal depolarizing shift (PDS), an important intracellular event during seizures. Although calcium spikes have not been demonstrated directly in neocortical cells, we have postulated (by analogy with hippocampal pyramidal cells) a dendritic calcium conductance and a 'slow potassium' conductance modulated by intracellular calcium ion. With these dendritic ionic conductances, the model is able to reproduce the following experimental features of neocortical pyramidal cells: the afterdepolarization and succeeding afterhyperpolarization after an antidromic spike, and the f-I (firing rate-injected current) curve. Some of the differences between 'fast' and 'slow' pyramidal tract neurons (PTNs) -- narrower spikes and a steeper f-I curve in the fast PTNs -- may be explained by differences in Hodgkin-Huxley potassium kinetics between the two kinds of cell. The same model which faithfully reproduces repetitive firing behavior also reproduces (given appropriate synaptic inputs) the following intracellular events recording during epileptic seizures: (a) a burst of action potentials superimposed on and followed by a PDS, and (b) rapid repetitive firing succeeded by an IPSP. Thus, a single set of parameters can reporduce both normal physiological behavior and 'epileptic' behavior: the particular behavior seen depending on how the cell is stimulated. This overall result is the same as for our model of the CA1 hippocampal cell. It suggests that certain acutely acting epileptogenic agents, e.g. penicillin, may act by increasing synaptic input (perhaps both excitatory and inhibitory) to pyramidal cells, rather than by altering their membrane properties. As in our CA1 hippocampal cell model, bursting seems to be a phenomenon generated by the apical dendrite."}
{"id": "PMID:226217", "title": "Some aspects of the organization of the lateral geniculate nucleus in Galago senegalensis revealed by using horseradish peroxidase to label relay neurons.", "content": "Following injection of horseradish peroxidase into area 17 of the prosimian Galago senegalensis, columns of labeled neurons are seen in the dorsal lateral geniculate nucleus extending through all cell layers. Individual counts of the number of labeled and unlabeled neurons reveal that from 91 to 98% of all neurons within these densely labeled columns are labeled. These results indicate that most of the neurons within the LGN of the bushbaby project to striate cortex. Average diameter measurements of labeled and unlabeled cells within the labeled columns were used to determine whether cell layers could be separated into two types (parvocellular and magnocellular) or three types (small, medium, and large) on the basis of cell body size. These measurements indicate that the LGN of the bushbaby is composed of two layers each of small (layers 4 and 5), medium (layers 3 and 6), and large (layers 1 and 2) relay neurons. These observations are consistent with the conclusion that layers 1 and 2 in the LGN of Galago are homologous with the magnocellular layers, and layers 3 and 6 homologous with the parvocellular layers, identified in the LGN of New and Old World monkeys.", "contents": "Some aspects of the organization of the lateral geniculate nucleus in Galago senegalensis revealed by using horseradish peroxidase to label relay neurons. Following injection of horseradish peroxidase into area 17 of the prosimian Galago senegalensis, columns of labeled neurons are seen in the dorsal lateral geniculate nucleus extending through all cell layers. Individual counts of the number of labeled and unlabeled neurons reveal that from 91 to 98% of all neurons within these densely labeled columns are labeled. These results indicate that most of the neurons within the LGN of the bushbaby project to striate cortex. Average diameter measurements of labeled and unlabeled cells within the labeled columns were used to determine whether cell layers could be separated into two types (parvocellular and magnocellular) or three types (small, medium, and large) on the basis of cell body size. These measurements indicate that the LGN of the bushbaby is composed of two layers each of small (layers 4 and 5), medium (layers 3 and 6), and large (layers 1 and 2) relay neurons. These observations are consistent with the conclusion that layers 1 and 2 in the LGN of Galago are homologous with the magnocellular layers, and layers 3 and 6 homologous with the parvocellular layers, identified in the LGN of New and Old World monkeys."}
{"id": "PMID:226218", "title": "Subcellular localization of luteinizing hormone releasing hormone degrading activity in the hypothalamus.", "content": "The in vitro degradation of endogenous as well as exogenous luteinizing hormone releasing hormone (LHRH) by subcellular fractions of rat hypothalamic tissue was studied. Endogenous LHRH, localized an isolated nerve terminals (synaptosomes), was found to be resistant to enzymatic degradation (60 min, 37 degrees C) as long as the synaptosomal membrane remained intact. Endogenous LHRH was rapidly degraded by the 900 x g supernatant fluid and cytosol but not by myelin/microsomes, intact synaptosomes, or mitochondria. Lysed synaptosomes rapidly degraded exogenous LHRH. The LHRH degrading activity of synaptosomes was highly concentrated in the 'synaptosol', i.e., the cytosol of the nerve terminal. These data suggest that the LHRH degrading activity of the rat hypothalamus is a readily solubilized component of neurons, and possibly of non-neuronal cells.", "contents": "Subcellular localization of luteinizing hormone releasing hormone degrading activity in the hypothalamus. The in vitro degradation of endogenous as well as exogenous luteinizing hormone releasing hormone (LHRH) by subcellular fractions of rat hypothalamic tissue was studied. Endogenous LHRH, localized an isolated nerve terminals (synaptosomes), was found to be resistant to enzymatic degradation (60 min, 37 degrees C) as long as the synaptosomal membrane remained intact. Endogenous LHRH was rapidly degraded by the 900 x g supernatant fluid and cytosol but not by myelin/microsomes, intact synaptosomes, or mitochondria. Lysed synaptosomes rapidly degraded exogenous LHRH. The LHRH degrading activity of synaptosomes was highly concentrated in the 'synaptosol', i.e., the cytosol of the nerve terminal. These data suggest that the LHRH degrading activity of the rat hypothalamus is a readily solubilized component of neurons, and possibly of non-neuronal cells."}
{"id": "PMID:226219", "title": "Morphine derivatives with diminished opiate receptor potency show enhanced central excitatory activity.", "content": "Central excitatory potency of morphine administered by cerebroventricular infusion in enhanced in derivatives substituted at the 3-position (phenolic group) and/or 6-position (alcoholic group). Morphine-3-glucuronide is several hundred times more potent than morphine in evoking dose-related hyperactive motor behavior which can progress to lethal convulsions. Excitatory potencies in decreasing order are: (1) 3-glucuronide; (2) 3-SO4; (3) 3-OAc, 6-OAc (heroin); (4) 6-OAc; (5) 3-OAc; (6) 3-OH, 6-OH (morphine); (7) 3-OCH3 (codeine); (8) 3-OCH3, 6-OCH3 (thebaine). Levorphanol, lacking a 6-OH group, is devoid of excitatory actions. In this series of substituted morphines, there is an inverse relationship between opiate receptor binding potency and central excitatory potency, but codeine and thebaine behave anomalously. These findings are compatible with the hypothesis that morphine acts upon a species of receptor which mediates behavioral and EEG excitation and is distinct from the recognized opiate receptor mediating sedation and analgesia.", "contents": "Morphine derivatives with diminished opiate receptor potency show enhanced central excitatory activity. Central excitatory potency of morphine administered by cerebroventricular infusion in enhanced in derivatives substituted at the 3-position (phenolic group) and/or 6-position (alcoholic group). Morphine-3-glucuronide is several hundred times more potent than morphine in evoking dose-related hyperactive motor behavior which can progress to lethal convulsions. Excitatory potencies in decreasing order are: (1) 3-glucuronide; (2) 3-SO4; (3) 3-OAc, 6-OAc (heroin); (4) 6-OAc; (5) 3-OAc; (6) 3-OH, 6-OH (morphine); (7) 3-OCH3 (codeine); (8) 3-OCH3, 6-OCH3 (thebaine). Levorphanol, lacking a 6-OH group, is devoid of excitatory actions. In this series of substituted morphines, there is an inverse relationship between opiate receptor binding potency and central excitatory potency, but codeine and thebaine behave anomalously. These findings are compatible with the hypothesis that morphine acts upon a species of receptor which mediates behavioral and EEG excitation and is distinct from the recognized opiate receptor mediating sedation and analgesia."}
{"id": "PMID:226224", "title": "Cocaine and D-amphetamine induce changes in central beta-adrenoceptor sensitivity: effects of acute and chronic drug treatment.", "content": "The effects of acute and chronic treatment with psychomotor stimulants on specific binding of [3H]dihydroalprenolol to beta-adrenoceptors in rat brain were examined. At a dose of 10 mg/kg both acute and chronic treatment with cocaine and chronic treatment with D-amphetamine (10 mg/kg) caused increased binding of [3H]dihydroalprenolol. The molecular mechanism for this enhanced binding appears to be augmentation of the density of beta-adrenoceptors in rat brain. At a lower dose (5 mg/kg), however, chronic administration of D-amphetamine caused a decrease in the density of beta-adrenoceptors in rat brain. Chronic treatment with either D-amphetamine (10 mg/kg) or cocaine induced a marked increase in the magnitude of cyclic AMP accumulation in rat brain slices elicited by norepinephrine. Acute as well as chronic administration of D-amphetamine in vivo inhibited the temperature-dependent uptake of [3H]norepinephrine in rat brain synaptosomal homogenates, but no such inhibition was observed after chronic or acute treatment with cocaine. The results suggest that psychomotor stimulants induce beta-adrenoceptor supersensitivity which may be involved in the phenomenon of reverse tolerance and possibly psychosis in humans. The development of beta-adrenoceptor supersensitivity does not appear to be mediated through alterations in norepinephrine transport at the presynaptic sites.", "contents": "Cocaine and D-amphetamine induce changes in central beta-adrenoceptor sensitivity: effects of acute and chronic drug treatment. The effects of acute and chronic treatment with psychomotor stimulants on specific binding of [3H]dihydroalprenolol to beta-adrenoceptors in rat brain were examined. At a dose of 10 mg/kg both acute and chronic treatment with cocaine and chronic treatment with D-amphetamine (10 mg/kg) caused increased binding of [3H]dihydroalprenolol. The molecular mechanism for this enhanced binding appears to be augmentation of the density of beta-adrenoceptors in rat brain. At a lower dose (5 mg/kg), however, chronic administration of D-amphetamine caused a decrease in the density of beta-adrenoceptors in rat brain. Chronic treatment with either D-amphetamine (10 mg/kg) or cocaine induced a marked increase in the magnitude of cyclic AMP accumulation in rat brain slices elicited by norepinephrine. Acute as well as chronic administration of D-amphetamine in vivo inhibited the temperature-dependent uptake of [3H]norepinephrine in rat brain synaptosomal homogenates, but no such inhibition was observed after chronic or acute treatment with cocaine. The results suggest that psychomotor stimulants induce beta-adrenoceptor supersensitivity which may be involved in the phenomenon of reverse tolerance and possibly psychosis in humans. The development of beta-adrenoceptor supersensitivity does not appear to be mediated through alterations in norepinephrine transport at the presynaptic sites."}
{"id": "PMID:226226", "title": "Suppression of retinal spike discharge by dipropylacetate (Depakene): a possible involvement of GABA.", "content": "Effects of dipropylacetate (DPA) were studied on spike discharges in the isolated carp retina. (1) DPA, applied electrophoretically or by pressure-microinjection in the vicinity of the recording electrode at the inner plexiform layer, consistently activated spike discharges. (2) DPA introduced into the perfusate produced complex actions; some units responded to DPA with an initial activation followed by suppression of spike discharges. (3) When gamma-aminobutyric acid (GABA) was applied electrophoretically together with perfusion of DPA, the depressing effect was greater than that obtained with each of these compounds alone. Bicuculline in the perfusate markedly attenuated the depressing actions of GABA or DPA singly, or in combination. (4) It is concluded that the delayed suppression of spike discharges by perfused DPA appears to be mediated by GABA-receptors on ganglion cells in the carp retina.", "contents": "Suppression of retinal spike discharge by dipropylacetate (Depakene): a possible involvement of GABA. Effects of dipropylacetate (DPA) were studied on spike discharges in the isolated carp retina. (1) DPA, applied electrophoretically or by pressure-microinjection in the vicinity of the recording electrode at the inner plexiform layer, consistently activated spike discharges. (2) DPA introduced into the perfusate produced complex actions; some units responded to DPA with an initial activation followed by suppression of spike discharges. (3) When gamma-aminobutyric acid (GABA) was applied electrophoretically together with perfusion of DPA, the depressing effect was greater than that obtained with each of these compounds alone. Bicuculline in the perfusate markedly attenuated the depressing actions of GABA or DPA singly, or in combination. (4) It is concluded that the delayed suppression of spike discharges by perfused DPA appears to be mediated by GABA-receptors on ganglion cells in the carp retina."}
{"id": "PMID:226230", "title": "Locus coeruleus and substantia nigra: involvement in morphine-induced behavior.", "content": "Cats pretreated with morphine (5 mg/kg, IP) received naloxone into the area of the locus coeruleus (LC) or the area of the substantia nigra (SN). The LC-treated animals stopped the morphine-induced stereotyped behavior and showed normal but hyperactive behavior. The SN-treated animals, however, ceased their movements of the head and the forelegs, adopted a rigid posture with extended forelegs and became hypoactive. It is concluded that both the LC area, which contains noradrenergic cell bodies, and the SN area, which contains dopaminergic cell bodies, are sites of action of morphine on behavior.", "contents": "Locus coeruleus and substantia nigra: involvement in morphine-induced behavior. Cats pretreated with morphine (5 mg/kg, IP) received naloxone into the area of the locus coeruleus (LC) or the area of the substantia nigra (SN). The LC-treated animals stopped the morphine-induced stereotyped behavior and showed normal but hyperactive behavior. The SN-treated animals, however, ceased their movements of the head and the forelegs, adopted a rigid posture with extended forelegs and became hypoactive. It is concluded that both the LC area, which contains noradrenergic cell bodies, and the SN area, which contains dopaminergic cell bodies, are sites of action of morphine on behavior."}
{"id": "PMID:226231", "title": "Intra- and interganglionic synaptic connections in the CNS of Aplysia.", "content": "Synaptic connections were found between two groups of neurons in the CNS of Aplysia, the cerebral ganglion A and B cluster neurons which are involved in the control of pedal and parapodial movements and neurons in the pleural ganglion which has been shown to modulate locomotion. The A and B neurons made synaptic connections in both the cerebral and pleural ganglia. Pleural neurons had synaptic connections among themselves and with A and B neurons. The A neurons made excitatory monosynaptic connections with the B neurons and a minimum of 6 pleural neurons including the left giant cell (LGC). All of the A neuron synapses found were excitatory. The B neurons received excitatory synaptic input from two other groups of neurons in the cerebral ganglion and both excitatory and inhibitory input from pleural neurons. The latter were identified on the basis of their synaptic connections with the LGC and A neurons. The B neurons and LGC had several common synaptic inputs. The A neurons received monosynaptic input from only 2 pleural neurons. Complex synaptic circuits between A and B neurons and pleural neurons were found. These included recurrent inhibition of B neurons by A neurons via a pleural interneuron, feedforward summation of A neuron synaptic input to the LGC, and reciprocal excitatory synaptic connections between B and the pleural neurons. The activity of the B neurons was modulated by direct inhibitory and excitatory synaptic connections from pleural neurons. The A neurons were modulated primarily by a polysynaptic pathway through the B neurons. The modulation of cerebral A and B neurons by pleural neurons is consistent with behavioral results obtained studying locomotion.", "contents": "Intra- and interganglionic synaptic connections in the CNS of Aplysia. Synaptic connections were found between two groups of neurons in the CNS of Aplysia, the cerebral ganglion A and B cluster neurons which are involved in the control of pedal and parapodial movements and neurons in the pleural ganglion which has been shown to modulate locomotion. The A and B neurons made synaptic connections in both the cerebral and pleural ganglia. Pleural neurons had synaptic connections among themselves and with A and B neurons. The A neurons made excitatory monosynaptic connections with the B neurons and a minimum of 6 pleural neurons including the left giant cell (LGC). All of the A neuron synapses found were excitatory. The B neurons received excitatory synaptic input from two other groups of neurons in the cerebral ganglion and both excitatory and inhibitory input from pleural neurons. The latter were identified on the basis of their synaptic connections with the LGC and A neurons. The B neurons and LGC had several common synaptic inputs. The A neurons received monosynaptic input from only 2 pleural neurons. Complex synaptic circuits between A and B neurons and pleural neurons were found. These included recurrent inhibition of B neurons by A neurons via a pleural interneuron, feedforward summation of A neuron synaptic input to the LGC, and reciprocal excitatory synaptic connections between B and the pleural neurons. The activity of the B neurons was modulated by direct inhibitory and excitatory synaptic connections from pleural neurons. The A neurons were modulated primarily by a polysynaptic pathway through the B neurons. The modulation of cerebral A and B neurons by pleural neurons is consistent with behavioral results obtained studying locomotion."}
{"id": "PMID:226232", "title": "Role of interganglionic synaptic connections in the control of pedal and parapodial movements in Aplysia.", "content": "Locomotion in Aplysia can be elicited by food chemosensory, tactile, proprioceptive and nociceptive stimuli. The effects of these stimuli on cerebral B neurons, pleural neurons and motor activity in the foot were examined and the behavioral roles of identified synaptic connections among these neurons investigated in semi-intact preparations. The motor effects of intracellular stimulation of pleural neurons were determined. Sensory stimulation elicited spiking in the left giant cell (LGC) in quiescent preparations. When the LGC was spontaneously bursting, sensory stimulation caused decreased interburst intervals and increased burst durations. Following sensory stimulation, LGC firing was correlated with motor activity in the foot. Intracellular stimulation of the LGC evoked contractions in the foot and parapodia. Pleural neurons which produced EPSPs in the LGC and/or B neurons were excited by sensory stimuli that elicit locomotion and when driven caused contractions in the foot. Pleural neurons which inhibited the B neurons were excited by nociceptive stimuli that inhibit normal locomotion, and were inhibited by tactile and chemosensory stimulation of the tentacles which excited the B neurons and can elicit normal locomotion. Intracellular stimulation of the neurons which produced IPSPs in the B neurons evoked contractions in the posterior foot suggesting a motor function in nociceptive induced withdrawal. The synaptic connections between pleural and cerebral neurons are consistent with the proposed modulatory role of the pleural ganglion in locomotion, and may account for changes in locomotion with result from cerebro-pleural connective lesions.", "contents": "Role of interganglionic synaptic connections in the control of pedal and parapodial movements in Aplysia. Locomotion in Aplysia can be elicited by food chemosensory, tactile, proprioceptive and nociceptive stimuli. The effects of these stimuli on cerebral B neurons, pleural neurons and motor activity in the foot were examined and the behavioral roles of identified synaptic connections among these neurons investigated in semi-intact preparations. The motor effects of intracellular stimulation of pleural neurons were determined. Sensory stimulation elicited spiking in the left giant cell (LGC) in quiescent preparations. When the LGC was spontaneously bursting, sensory stimulation caused decreased interburst intervals and increased burst durations. Following sensory stimulation, LGC firing was correlated with motor activity in the foot. Intracellular stimulation of the LGC evoked contractions in the foot and parapodia. Pleural neurons which produced EPSPs in the LGC and/or B neurons were excited by sensory stimuli that elicit locomotion and when driven caused contractions in the foot. Pleural neurons which inhibited the B neurons were excited by nociceptive stimuli that inhibit normal locomotion, and were inhibited by tactile and chemosensory stimulation of the tentacles which excited the B neurons and can elicit normal locomotion. Intracellular stimulation of the neurons which produced IPSPs in the B neurons evoked contractions in the posterior foot suggesting a motor function in nociceptive induced withdrawal. The synaptic connections between pleural and cerebral neurons are consistent with the proposed modulatory role of the pleural ganglion in locomotion, and may account for changes in locomotion with result from cerebro-pleural connective lesions."}
{"id": "PMID:226233", "title": "Raphe projections to the locus coeruleus in the rat.", "content": "Afferent projections to the locus coeruleus from the various raphe nuclei, particularly of the midbrain (nuclei raphe dorsalis and medianus) and pons (nuclei raphe pontis and magnus), have been studied in the rat by retrograde transport methods using horseradish peroxidase (HRP). The locus coeruleus, in both its dorsomedial and ventrolateral divisions, and in its various anterior-posterior components, were injected with 0.05 microliters of horseradish peroxidase following which various structures of the brainstem, particularly the raphe nuclei, were examined for HRP reactive cells. It was found that injections in most components of the locus coeruleus were associated with HRP positive cells in varying degrees of density in the nuclei raphe dorsalis, medianus, pontis, and magnus, with considerably sparser labelling in the anterior aspects of the medullary raphe nuclei pallidus and obscurus. Labelled cells were also seen in the nuclei of the solitary tract, contralateral locus coeruleus. lateral reticular areas of the pons and midbrain, nuclei pontis oralis and caudalis, vestibular nuclei, mesencephalic nucleus of the trigeminal nerve, fastigial nuclei of cerebellum and medial parabrachial nuclei. These data, showing widespread innervation of the locus coeruleus from all raphe nuclei, as well as many other brainstem areas, in the rat support the general view of heavy innervation of the locus coeruleus from both extra-raphe and raphe nulcei. These latter raphe projections, probably serotonergic in nature, provide anatomical support for the various experiments indicating considerable regulation of locus coeruleus activities, such as phasic events of REM sleep, among other, by widespread projections from most raphe nuclei was well as several other regions of the brainstem.", "contents": "Raphe projections to the locus coeruleus in the rat. Afferent projections to the locus coeruleus from the various raphe nuclei, particularly of the midbrain (nuclei raphe dorsalis and medianus) and pons (nuclei raphe pontis and magnus), have been studied in the rat by retrograde transport methods using horseradish peroxidase (HRP). The locus coeruleus, in both its dorsomedial and ventrolateral divisions, and in its various anterior-posterior components, were injected with 0.05 microliters of horseradish peroxidase following which various structures of the brainstem, particularly the raphe nuclei, were examined for HRP reactive cells. It was found that injections in most components of the locus coeruleus were associated with HRP positive cells in varying degrees of density in the nuclei raphe dorsalis, medianus, pontis, and magnus, with considerably sparser labelling in the anterior aspects of the medullary raphe nuclei pallidus and obscurus. Labelled cells were also seen in the nuclei of the solitary tract, contralateral locus coeruleus. lateral reticular areas of the pons and midbrain, nuclei pontis oralis and caudalis, vestibular nuclei, mesencephalic nucleus of the trigeminal nerve, fastigial nuclei of cerebellum and medial parabrachial nuclei. These data, showing widespread innervation of the locus coeruleus from all raphe nuclei, as well as many other brainstem areas, in the rat support the general view of heavy innervation of the locus coeruleus from both extra-raphe and raphe nulcei. These latter raphe projections, probably serotonergic in nature, provide anatomical support for the various experiments indicating considerable regulation of locus coeruleus activities, such as phasic events of REM sleep, among other, by widespread projections from most raphe nuclei was well as several other regions of the brainstem."}
{"id": "PMID:226237", "title": "[Modification of a method to study cell fusion induced in vitro by viruses].", "content": "A studying method of viruses induced cell-fusion is described, using monolayers of Vero monkey cells. Nature and density of cells and infection multiplicity are studied. The sensibility is equal to 4 hemagglutining units of Senda\u00ef and accuracy about +/- 3 % of polykaryocytosis. Quantification. comparison and kinetics study of cell-fusion are allowed by this method which may lead to systematic and routine exploration of cell-fusion ability of biological extracts from slow degenerative diseases of the human central nervous system.", "contents": "[Modification of a method to study cell fusion induced in vitro by viruses]. A studying method of viruses induced cell-fusion is described, using monolayers of Vero monkey cells. Nature and density of cells and infection multiplicity are studied. The sensibility is equal to 4 hemagglutining units of Senda\u00ef and accuracy about +/- 3 % of polykaryocytosis. Quantification. comparison and kinetics study of cell-fusion are allowed by this method which may lead to systematic and routine exploration of cell-fusion ability of biological extracts from slow degenerative diseases of the human central nervous system."}
{"id": "PMID:226238", "title": "[In vitro fusion ability of agents causing slow diseases of the central nervous system].", "content": "The authors study cell fusion in vitro induced by two kinds of slow viruses : visna virus of sheep and scrapie of mouse and Creutzfeldt-Jakob disease of man agents. Cell-fusion induced by visna virus is either slow and late occuring (fusion from within) or early and rapid (fusion from without) according to experimental conditions. Whereas, cell-fusion induced by spongiform encephalopathies agents is only of slow appearance, looking an endogenous phenomenon.", "contents": "[In vitro fusion ability of agents causing slow diseases of the central nervous system]. The authors study cell fusion in vitro induced by two kinds of slow viruses : visna virus of sheep and scrapie of mouse and Creutzfeldt-Jakob disease of man agents. Cell-fusion induced by visna virus is either slow and late occuring (fusion from within) or early and rapid (fusion from without) according to experimental conditions. Whereas, cell-fusion induced by spongiform encephalopathies agents is only of slow appearance, looking an endogenous phenomenon."}
{"id": "PMID:226239", "title": "[Nuclear inclusions in the posterior epithelium of the rat pituitary cleft].", "content": "Microfilamentous nuclear inculsions have been found at the ultrastructural level in the posterior epithelium of the rat pituitary cleft. They appear strictly located in ciliate cells of this epithelium. The microfilaments (7-8 nm in diameter) are gathered as a bundle. Their length is up to several microns and their average diameter is 0,35 micron. They can only be observed in adult rats.", "contents": "[Nuclear inclusions in the posterior epithelium of the rat pituitary cleft]. Microfilamentous nuclear inculsions have been found at the ultrastructural level in the posterior epithelium of the rat pituitary cleft. They appear strictly located in ciliate cells of this epithelium. The microfilaments (7-8 nm in diameter) are gathered as a bundle. Their length is up to several microns and their average diameter is 0,35 micron. They can only be observed in adult rats."}
{"id": "PMID:226235", "title": "Fornix transection: discrimination between neuropeptide effects on attention and memory.", "content": "Transection of the fornix and the stria terminalis completely blocks the inhibitory action of ACTH 4-10 on extinction of a conditioned avoidance response (CAR), whereas this effect of the vasopressin analogue des-glycinamide-lysine-vasopressin (DG-LVP) is not affected. These data indicate that the behavioral effect of DG-LVP may be localized to certain anatomical substrates, while ACTH 4-10 needs an intact limbic system as a functional substrate for its effect on avoidance behavior. This differential effect of fornicotomy may also be interpreted as a discrimination between the effects of these neuropeptides on attention or on memory consolidation. Additionally, transection of the fornix and the stria terminalis induces an increase in motor responsiveness to an electric footshock (EFS) and a facilitation of acquisition of a CAR.", "contents": "Fornix transection: discrimination between neuropeptide effects on attention and memory. Transection of the fornix and the stria terminalis completely blocks the inhibitory action of ACTH 4-10 on extinction of a conditioned avoidance response (CAR), whereas this effect of the vasopressin analogue des-glycinamide-lysine-vasopressin (DG-LVP) is not affected. These data indicate that the behavioral effect of DG-LVP may be localized to certain anatomical substrates, while ACTH 4-10 needs an intact limbic system as a functional substrate for its effect on avoidance behavior. This differential effect of fornicotomy may also be interpreted as a discrimination between the effects of these neuropeptides on attention or on memory consolidation. Additionally, transection of the fornix and the stria terminalis induces an increase in motor responsiveness to an electric footshock (EFS) and a facilitation of acquisition of a CAR."}
{"id": "PMID:226241", "title": "The identification of alpha-adrenergic receptors in adipose tissue by [3H]dihydroergocryptine binding.", "content": "The 3H-labelled alpha-adrenergic antagonist dihydroergocryptine has been found to bind specifically to hamster white adipocyte membranes. Binding is rapid and is inhibited by alpha but not beta antagonists. In addition, adrenergic agonists compete for this binding site in order of affinities equal to their activity as alpha-adrenergic agonists. The (-) stereoisomer of adrenaline is 10 times more potent than the (+) stereoisomer in inhibiting binding.", "contents": "The identification of alpha-adrenergic receptors in adipose tissue by [3H]dihydroergocryptine binding. The 3H-labelled alpha-adrenergic antagonist dihydroergocryptine has been found to bind specifically to hamster white adipocyte membranes. Binding is rapid and is inhibited by alpha but not beta antagonists. In addition, adrenergic agonists compete for this binding site in order of affinities equal to their activity as alpha-adrenergic agonists. The (-) stereoisomer of adrenaline is 10 times more potent than the (+) stereoisomer in inhibiting binding."}
{"id": "PMID:226242", "title": "Influence of choline and ethanolamine administration on choline and ethanolamine phosphorylating activities of mouse liver and kidney.", "content": "The administration of ethanolamine to adult male mice resulted in a significant increase in ethanolamine kinase activity in liver and kidney. Similarly, choline administration resulted in a significant increase in choline kinase activity in liver and kidney. The administration of ethanolamine resulted in enhancement of choline kinase activity concomitantly with ethanolamine kinase activity in liver and kidney. The administration of choline, however, did not result in any significant increase in ethanolamine kinase activity in liver or kidney. Cycloheximide administration along with choline-ethanolamine prevented the increase in kinase activity in liver and kidney. The results obtained have been discussed in relation to the regulatory role of choline kinase and ethanolamine kinase by de novo synthesis in response to enhanced substrate concentration, the secondary nature of choline kinase induction on ethanolamine administration, and possible distinction between choline kinase and ethanolamine kinase.", "contents": "Influence of choline and ethanolamine administration on choline and ethanolamine phosphorylating activities of mouse liver and kidney. The administration of ethanolamine to adult male mice resulted in a significant increase in ethanolamine kinase activity in liver and kidney. Similarly, choline administration resulted in a significant increase in choline kinase activity in liver and kidney. The administration of ethanolamine resulted in enhancement of choline kinase activity concomitantly with ethanolamine kinase activity in liver and kidney. The administration of choline, however, did not result in any significant increase in ethanolamine kinase activity in liver or kidney. Cycloheximide administration along with choline-ethanolamine prevented the increase in kinase activity in liver and kidney. The results obtained have been discussed in relation to the regulatory role of choline kinase and ethanolamine kinase by de novo synthesis in response to enhanced substrate concentration, the secondary nature of choline kinase induction on ethanolamine administration, and possible distinction between choline kinase and ethanolamine kinase."}
{"id": "PMID:226243", "title": "The indirect fluorescent antibody technique as a method for detecting antibodies in aborted fetuses.", "content": "In this investigation the indirect fluorescent antibody technique was used to titrate antibodies in bovine sera to parainfluenza 3, infectious bovine rhinotracheitis virus and bovine viral diarrhea virus. These results were compared to those determined on the same samples by hemagglutination inhibition for parainfluenza 3 virus and serum neutralization for bovine virus diarrhea and infectious bovine rhinotracheitis virus. The results of the serological methods agreed closely. The indirect fluorescent antibody technique is a rapid and sensitive method for detecting antibodies and the procedure lends itself to use in diagnostic laboratories. In addition to the above viruses the presence or absence of antibodies to bovine coronavirus and bovine adenovirus 3 were determined by the indirect fluorescent antibody technique in thoracic fluids from 100 aborted fetuses and 50 nonaborted fetuses. Results on these samples were not compared to hemagglutination inhibition or serum neutralization as the condition of fluid samples from aborted fetuses renders interpretation of such tests unreliable. Antibodies to one or more viruses were detected in 30 of the 100 aborted fetuses and in seven of the 50 nonaborted fetuses. Antibodies to more than one agent were detected in eleven of the 100 aborted and in one of the 50 nonaborted fetuses. Reasons for this occurrence and application of the test in determination of causes of abortion are discussed.", "contents": "The indirect fluorescent antibody technique as a method for detecting antibodies in aborted fetuses. In this investigation the indirect fluorescent antibody technique was used to titrate antibodies in bovine sera to parainfluenza 3, infectious bovine rhinotracheitis virus and bovine viral diarrhea virus. These results were compared to those determined on the same samples by hemagglutination inhibition for parainfluenza 3 virus and serum neutralization for bovine virus diarrhea and infectious bovine rhinotracheitis virus. The results of the serological methods agreed closely. The indirect fluorescent antibody technique is a rapid and sensitive method for detecting antibodies and the procedure lends itself to use in diagnostic laboratories. In addition to the above viruses the presence or absence of antibodies to bovine coronavirus and bovine adenovirus 3 were determined by the indirect fluorescent antibody technique in thoracic fluids from 100 aborted fetuses and 50 nonaborted fetuses. Results on these samples were not compared to hemagglutination inhibition or serum neutralization as the condition of fluid samples from aborted fetuses renders interpretation of such tests unreliable. Antibodies to one or more viruses were detected in 30 of the 100 aborted fetuses and in seven of the 50 nonaborted fetuses. Antibodies to more than one agent were detected in eleven of the 100 aborted and in one of the 50 nonaborted fetuses. Reasons for this occurrence and application of the test in determination of causes of abortion are discussed."}
{"id": "PMID:226244", "title": "Evaluation of the agar-gel immunodiffusion test for the detection of precipitating antibodies against progressive pneumonia virus of sheep.", "content": "Various cell cultures were evaluated for their ability to support progressive pneumonia virus infection in vitro. Ovine trachea cells supported progressive pneumonia virus infection for an extended time,were extremely durable and could be passaged up until 30 passages. Progressive pneumonia virus infected ovine trachea cells were then used for the production of antigen for agar-gel immunodiffusion. A method for concentrating antigen, diafiltration, was compared to dialysis against polyethylene glycol. Using diafiltration, the concentrated virus was easily quantitated, less viscous (and therefore easier to apply) and only produced one precipitation line. Agar-gel immunodiffusion was used to survey 401 animals from two sheep flocks. One flock (96 sheep) was free of progressive pneumonia while the other flock had 111 of 305 total animals positive for precipitating antibodies. The incidence of precipitating antibodies in sheep ranged from 23% for yearling ewes to 80% in ewes seven years old.", "contents": "Evaluation of the agar-gel immunodiffusion test for the detection of precipitating antibodies against progressive pneumonia virus of sheep. Various cell cultures were evaluated for their ability to support progressive pneumonia virus infection in vitro. Ovine trachea cells supported progressive pneumonia virus infection for an extended time,were extremely durable and could be passaged up until 30 passages. Progressive pneumonia virus infected ovine trachea cells were then used for the production of antigen for agar-gel immunodiffusion. A method for concentrating antigen, diafiltration, was compared to dialysis against polyethylene glycol. Using diafiltration, the concentrated virus was easily quantitated, less viscous (and therefore easier to apply) and only produced one precipitation line. Agar-gel immunodiffusion was used to survey 401 animals from two sheep flocks. One flock (96 sheep) was free of progressive pneumonia while the other flock had 111 of 305 total animals positive for precipitating antibodies. The incidence of precipitating antibodies in sheep ranged from 23% for yearling ewes to 80% in ewes seven years old."}
{"id": "PMID:226245", "title": "Immune response of cattle to antigens obtained from bovine herpesvirus 1-infected tissue culture.", "content": "The ability of two antigens, termed EV and CM, derived from bovine herpesvirus 1 infected cultures to produce serum-virus neutralizing antibodies has been studied in cattle. Both EV and CM when inoculated with adjuvant induced significant increases in serum-virus neutralizing antibody titers. Control groups inoculated in a similar manner failed to induce significant increases in serum-virus neutralizing antibody. Some of the animals were vaccinated, then were bred, challenged with a virulent strain of bovine herpesvirus 1 and held until calving was completed. During this 18-month period titers declined slowly in the vaccinated animals. Proportionally there were fewer live calves born to the control cattle than to the CM vaccinated group but reduction was not large enough to conclude that this vaccine had protected the cattle against the abortigenic activity of bovine herpesvirus 1. Further challenge studies should be made to determine whether the administration of these antigens can prevent the subsequent onset of the clinical signs associated with bovine herpesvirus 1.", "contents": "Immune response of cattle to antigens obtained from bovine herpesvirus 1-infected tissue culture. The ability of two antigens, termed EV and CM, derived from bovine herpesvirus 1 infected cultures to produce serum-virus neutralizing antibodies has been studied in cattle. Both EV and CM when inoculated with adjuvant induced significant increases in serum-virus neutralizing antibody titers. Control groups inoculated in a similar manner failed to induce significant increases in serum-virus neutralizing antibody. Some of the animals were vaccinated, then were bred, challenged with a virulent strain of bovine herpesvirus 1 and held until calving was completed. During this 18-month period titers declined slowly in the vaccinated animals. Proportionally there were fewer live calves born to the control cattle than to the CM vaccinated group but reduction was not large enough to conclude that this vaccine had protected the cattle against the abortigenic activity of bovine herpesvirus 1. Further challenge studies should be made to determine whether the administration of these antigens can prevent the subsequent onset of the clinical signs associated with bovine herpesvirus 1."}
{"id": "PMID:226246", "title": "Aerosol stability of bovine parainfluenza type 3 virus.", "content": "Aerosols of bovine parainfluenza type 3 virus were generated with a Devilbiss 40 nebulizer from Eagle's minimum essential medium and nasal secretion from a non-infected calf and stored in a rotating drum at temperatures of 6 degrees C or 32 degrees C and relative humidities of 30% or 90%. The aerosols were sampled at seven minutes, one, two and three hours after the start of generation with an all glass impinger (AGI-30) and titrated for infectivity in cell cultures. Physical decay was determined by a rhodamine tracer technique. Media, temperature or relative humidity had little effect on the survival of parainfluenza type 3 virus during spraying (zero to seven minutes). During aging of aerosols at 32 degrees C and 30% relative humidity, parainfluenza type 3 virus was less stable in Eagle's minimum essential medium than in nasal secretion from a noninfected calf, but at 6 degrees C and 30% relative humidity, the virus was more stable in Eagle's minimum essential medium. At 32 degrees C, the virus was less stable during aging at 90% relative humidity than at 30% relative humidity. The virus was consistently more stable during aging of aerosols at 6 degrees C than at 32 degrees C.", "contents": "Aerosol stability of bovine parainfluenza type 3 virus. Aerosols of bovine parainfluenza type 3 virus were generated with a Devilbiss 40 nebulizer from Eagle's minimum essential medium and nasal secretion from a non-infected calf and stored in a rotating drum at temperatures of 6 degrees C or 32 degrees C and relative humidities of 30% or 90%. The aerosols were sampled at seven minutes, one, two and three hours after the start of generation with an all glass impinger (AGI-30) and titrated for infectivity in cell cultures. Physical decay was determined by a rhodamine tracer technique. Media, temperature or relative humidity had little effect on the survival of parainfluenza type 3 virus during spraying (zero to seven minutes). During aging of aerosols at 32 degrees C and 30% relative humidity, parainfluenza type 3 virus was less stable in Eagle's minimum essential medium than in nasal secretion from a noninfected calf, but at 6 degrees C and 30% relative humidity, the virus was more stable in Eagle's minimum essential medium. At 32 degrees C, the virus was less stable during aging at 90% relative humidity than at 30% relative humidity. The virus was consistently more stable during aging of aerosols at 6 degrees C than at 32 degrees C."}
{"id": "PMID:226247", "title": "Aerosol stability of bovine adenovirus type 3.", "content": "The WBR-1 strain of bovine adenovirus type 3 was suspended in Eagle's medium or bovine nasal secretion and atomized into a rotating drum at temperatures of 6 degrees C or 32 degrees C and relative humidities of 30% or 90%. Impinger samples of the aerosols were collected seven minutes, one, two and three hours postgeneration, and titrated for infectivity in embryonic bovine kidney cell cultures. Under certain conditions of temperature and relative humidity, the virus was more stable in aerosols of Eagle's medium than in nasal secretion. The bovine adenovirus was usually inactivated more rapidly at 30% relative humidity than at 90% relative humidity and during aging of the aerosols the virus was inactivated more rapidly at 32 degrees C than at 6 degrees C.", "contents": "Aerosol stability of bovine adenovirus type 3. The WBR-1 strain of bovine adenovirus type 3 was suspended in Eagle's medium or bovine nasal secretion and atomized into a rotating drum at temperatures of 6 degrees C or 32 degrees C and relative humidities of 30% or 90%. Impinger samples of the aerosols were collected seven minutes, one, two and three hours postgeneration, and titrated for infectivity in embryonic bovine kidney cell cultures. Under certain conditions of temperature and relative humidity, the virus was more stable in aerosols of Eagle's medium than in nasal secretion. The bovine adenovirus was usually inactivated more rapidly at 30% relative humidity than at 90% relative humidity and during aging of the aerosols the virus was inactivated more rapidly at 32 degrees C than at 6 degrees C."}
{"id": "PMID:226248", "title": "Maedi-visna in Canadian sheep.", "content": "Lesions of maedi-visna were seen in sheep from the institutional research flock of the Animal Research Institute, Research Branch, Agriculture Canada in Ottawa. Viral particles demonstrated by electron microscopy in tissue culture cells and serological results confirm the diagnosis of maedi-visna. The extent of the problem in this flock will be described in a future paper.", "contents": "Maedi-visna in Canadian sheep. Lesions of maedi-visna were seen in sheep from the institutional research flock of the Animal Research Institute, Research Branch, Agriculture Canada in Ottawa. Viral particles demonstrated by electron microscopy in tissue culture cells and serological results confirm the diagnosis of maedi-visna. The extent of the problem in this flock will be described in a future paper."}
{"id": "PMID:226249", "title": "Use of electron microscopy and an enzyme-linked immunosorbent assay for the detection of rotaviruses in neonatal calf diarrhea.", "content": "Electron microscopy and an enzyme-linked immunosorbent assay were compared for the diagnosis of rotaviruses associated with neonatal calf diarrhea. One hundred percent correlation was observed when 125 samples were tested by both techniques. Both techniques were equally efficient in detecting rotaviruses. The enzyme-linked immunosorbent assay was more sensitive but being specific could not detect other viruses.", "contents": "Use of electron microscopy and an enzyme-linked immunosorbent assay for the detection of rotaviruses in neonatal calf diarrhea. Electron microscopy and an enzyme-linked immunosorbent assay were compared for the diagnosis of rotaviruses associated with neonatal calf diarrhea. One hundred percent correlation was observed when 125 samples were tested by both techniques. Both techniques were equally efficient in detecting rotaviruses. The enzyme-linked immunosorbent assay was more sensitive but being specific could not detect other viruses."}
{"id": "PMID:226250", "title": "Cyclic nucleotides, calcium, bicarbonate, and protein secretion in canine pancreatic juice in response to cholecystokinin-pancreozymin.", "content": "The secretion of cyclic AMP, cyclic GMP, protein, calcium, and bicarbonate in the pancreatic juice of three nonanesthetized dogs with chronic gastric and duodenal Thomas cannulae has been studied. Intravenous infusions of increasing doses of cholecystokinin-pancreozymin (CCK) (1.5, 3, 6, 12, 24 Crick Harper-Raper (CHR) U kg-1 h-1) were administered together with a continuous submaximal dose of secretin (1 clinical unit (CU) kg-1 h-1). Doubling CCK doses every 45 min induced a parallel increase in the output of both cyclic nucleotides. Cyclic AMP output peaked at between 15 and 30 min for 3 and 6 U kg-1 h-1 of CCK and later for 12 and 24 U kg-1 h-1 of CCK whereas cyclic GMP output increased more constantly. Calcium output followed a pattern similar to that of cyclic GMP secretion. Flow rate and protein output attained their peaks at between 30 and 45 min. A strong linear correlation was found between the quantities of cyclic AMP, cyclic GMP, and the quantities of protein secreted in response to each CCK dose. This study demonstrates the presence of cyclic GMP in the canine pancreatic juice and the dose-dependent stimulation of the secretion of cyclic GMP and cyclic AMP by CCK in the presence of secretin.", "contents": "Cyclic nucleotides, calcium, bicarbonate, and protein secretion in canine pancreatic juice in response to cholecystokinin-pancreozymin. The secretion of cyclic AMP, cyclic GMP, protein, calcium, and bicarbonate in the pancreatic juice of three nonanesthetized dogs with chronic gastric and duodenal Thomas cannulae has been studied. Intravenous infusions of increasing doses of cholecystokinin-pancreozymin (CCK) (1.5, 3, 6, 12, 24 Crick Harper-Raper (CHR) U kg-1 h-1) were administered together with a continuous submaximal dose of secretin (1 clinical unit (CU) kg-1 h-1). Doubling CCK doses every 45 min induced a parallel increase in the output of both cyclic nucleotides. Cyclic AMP output peaked at between 15 and 30 min for 3 and 6 U kg-1 h-1 of CCK and later for 12 and 24 U kg-1 h-1 of CCK whereas cyclic GMP output increased more constantly. Calcium output followed a pattern similar to that of cyclic GMP secretion. Flow rate and protein output attained their peaks at between 30 and 45 min. A strong linear correlation was found between the quantities of cyclic AMP, cyclic GMP, and the quantities of protein secreted in response to each CCK dose. This study demonstrates the presence of cyclic GMP in the canine pancreatic juice and the dose-dependent stimulation of the secretion of cyclic GMP and cyclic AMP by CCK in the presence of secretin."}
{"id": "PMID:226251", "title": "Patterns of early and late discharges in somatotopically identified precentral neurons in awake monkeys in response to somatic inputs.", "content": "Extracellular recordings were made of single neurons in precentral cortex of awake monkeys. These neurons were somatotopically identified with respect to their responses to inputs from single joints or their somatic surround. Many of these neurons exhibited early (less than 50 ms) and late (greater than 50 ms) discharges in response to flexion or extension torques delivered about the wrist. With the monkey in a mode requiring opposition to the injected torque, all responsive neurons showed a parallel excitatory or inhibitory modification in the early and late discharges. This was true both for cells identified as wrist (flexion-extension) neurons and those identified as nonwrist (flexion-extension) neurons. These findings indicate that the reflex and voluntary components of percentral discharge invariably show a congruent functional response to a torque disturbance, for this particular instruction set.", "contents": "Patterns of early and late discharges in somatotopically identified precentral neurons in awake monkeys in response to somatic inputs. Extracellular recordings were made of single neurons in precentral cortex of awake monkeys. These neurons were somatotopically identified with respect to their responses to inputs from single joints or their somatic surround. Many of these neurons exhibited early (less than 50 ms) and late (greater than 50 ms) discharges in response to flexion or extension torques delivered about the wrist. With the monkey in a mode requiring opposition to the injected torque, all responsive neurons showed a parallel excitatory or inhibitory modification in the early and late discharges. This was true both for cells identified as wrist (flexion-extension) neurons and those identified as nonwrist (flexion-extension) neurons. These findings indicate that the reflex and voluntary components of percentral discharge invariably show a congruent functional response to a torque disturbance, for this particular instruction set."}
{"id": "PMID:226252", "title": "Structure-activity studies on the inhibition of gamma-aminobutyric acid uptake in brain slices by compounds related to nipecotic acid.", "content": "Various N-methyl derivatives of nipecotic acid and related compounds were tested as inhibitors of gamma-aminobutyric acid (GABA) uptake into mini slices. N-Methylnipecotic acid, N,N-dimethylnipecotic acid, N-methylguvacine, and N-methylnicotinic acid were effective inhibitors. None of them, however, were as potent as nipecotic acid itself. All the effective inhibitors, including nipecotic acid, also inhibited the uptake of L-proline, but to a much lesser extent. Four of the test compounds produced a depressant action on cerebral cortical neurons, but even N-methylisoguvacine, the most potent in this respect, was considerably less active than GABA. None of the test compounds caused any clearly discernible changes in the gross behaviour or appearance of mice in the 1-h period following intramuscular injection. It was concluded that methylation of the N atom of nipecotic acid and its derivatives was unlikely to lead to the development of agents with greater experimental or therapeutic potential than that of nipecotic acid itself, if the action of the agent was dependent on its effects on GABA uptake.", "contents": "Structure-activity studies on the inhibition of gamma-aminobutyric acid uptake in brain slices by compounds related to nipecotic acid. Various N-methyl derivatives of nipecotic acid and related compounds were tested as inhibitors of gamma-aminobutyric acid (GABA) uptake into mini slices. N-Methylnipecotic acid, N,N-dimethylnipecotic acid, N-methylguvacine, and N-methylnicotinic acid were effective inhibitors. None of them, however, were as potent as nipecotic acid itself. All the effective inhibitors, including nipecotic acid, also inhibited the uptake of L-proline, but to a much lesser extent. Four of the test compounds produced a depressant action on cerebral cortical neurons, but even N-methylisoguvacine, the most potent in this respect, was considerably less active than GABA. None of the test compounds caused any clearly discernible changes in the gross behaviour or appearance of mice in the 1-h period following intramuscular injection. It was concluded that methylation of the N atom of nipecotic acid and its derivatives was unlikely to lead to the development of agents with greater experimental or therapeutic potential than that of nipecotic acid itself, if the action of the agent was dependent on its effects on GABA uptake."}
{"id": "PMID:226253", "title": "The effects of cold-induced muscle spindle secondary activity on monosynaptic and stretch reflexes in the decerebrate cat.", "content": "The effects of muscle spindle secondary ending activity on the stretch reflex were studied in unanesthetized decerebrate cats. Activation of secondary endings was accomplished by reducing the muscle temperature. This has been shown to cause a sustained asynchronous discharge from secondary endings. Cooling of the medial gastrocnemius or lateral gastrocnemius-soleus muscles caused an increase in the phasic and tonic components of their stretch reflexes. Cooling of the relaxed medial gastrocnemius muscle caused similar increases in the components of the stretch reflex of the synergistic lateral gastrocnemius-soleus muscle and an increase in its monosynaptic reflex. It was concluded that the facilitatory autogenetic and synergistic effects of muscle cooling on the stretch and monosynaptic reflexes were brought about by activity in group II afferents from muscle spindle secondary endings and could not be ascribed to any other type of muscle receptor. These results support the concept of an excitatory role for the secondary endings of the muscle spindle in the stretch reflex of the decerebrate cat.", "contents": "The effects of cold-induced muscle spindle secondary activity on monosynaptic and stretch reflexes in the decerebrate cat. The effects of muscle spindle secondary ending activity on the stretch reflex were studied in unanesthetized decerebrate cats. Activation of secondary endings was accomplished by reducing the muscle temperature. This has been shown to cause a sustained asynchronous discharge from secondary endings. Cooling of the medial gastrocnemius or lateral gastrocnemius-soleus muscles caused an increase in the phasic and tonic components of their stretch reflexes. Cooling of the relaxed medial gastrocnemius muscle caused similar increases in the components of the stretch reflex of the synergistic lateral gastrocnemius-soleus muscle and an increase in its monosynaptic reflex. It was concluded that the facilitatory autogenetic and synergistic effects of muscle cooling on the stretch and monosynaptic reflexes were brought about by activity in group II afferents from muscle spindle secondary endings and could not be ascribed to any other type of muscle receptor. These results support the concept of an excitatory role for the secondary endings of the muscle spindle in the stretch reflex of the decerebrate cat."}
{"id": "PMID:226254", "title": "Neck muscle and trigeminal input to the upper cervical cord and lower medulla of the cat.", "content": "Experiments on chloralose-anaesthetized cats have shown that low-threshold neck muscle afferents project to laminae IV and V in the dorsal horn of the upper cervical cord, to lamina VI including the region which encompasses the central cervical nucleus, as well as to extensive regions of the ventral horn. At posterior medullary levels projections also exist to laminae IV, V, and VI of the spinal nucleus of V (although those to lamina IV are circumscribed), to the deep layers and lateral margin of the cuneate nucleus, and to the inferior olive. These projections are both from low- and high-threshold afferents. Evidence of a functional relationship between the trigeminal and neck muscle afferent system was found both in the upper cervical cord and lower medulla. About 40% of units in both regions receive a convergent input and when convergence could not be demonstrated, prior stimulation of one modality in some instances affected the responsiveness of the unit to the other modality. A motor role was found for some trigeminal afferent projections to the upper cervical cord. Trigeminal afferents consistently activated antidromically identified motoneurons of splenius, biventer cervicis, and complexus.", "contents": "Neck muscle and trigeminal input to the upper cervical cord and lower medulla of the cat. Experiments on chloralose-anaesthetized cats have shown that low-threshold neck muscle afferents project to laminae IV and V in the dorsal horn of the upper cervical cord, to lamina VI including the region which encompasses the central cervical nucleus, as well as to extensive regions of the ventral horn. At posterior medullary levels projections also exist to laminae IV, V, and VI of the spinal nucleus of V (although those to lamina IV are circumscribed), to the deep layers and lateral margin of the cuneate nucleus, and to the inferior olive. These projections are both from low- and high-threshold afferents. Evidence of a functional relationship between the trigeminal and neck muscle afferent system was found both in the upper cervical cord and lower medulla. About 40% of units in both regions receive a convergent input and when convergence could not be demonstrated, prior stimulation of one modality in some instances affected the responsiveness of the unit to the other modality. A motor role was found for some trigeminal afferent projections to the upper cervical cord. Trigeminal afferents consistently activated antidromically identified motoneurons of splenius, biventer cervicis, and complexus."}
{"id": "PMID:226256", "title": "The effect of ambient temperature on beta-adrenergic responsiveness in rats.", "content": "The responses of tail skin and colonic temperatures of female rats to ambient temperatures of 20, 22, 24, 26, 28, and 30 degrees C were measured. Within this range, colonic temperature was stable while tail skin temperature increased linearly with increasing ambient temperature. Administration of the beta-adrenergic agonist, d,l-isoproterenol, at 10.0, 25.0, and 62.5 micrograms/kg, sc, at each ambient temperature was accompanied by increases in tail skin and colonic temperatures that were dependent on both the dose of isoproterenol administered and the ambient temperature. The integrated responses of tail skin temperature following administration of the three doses of isoproterenol were maximal at an ambient temperature of 26 degrees C while the integrated responses of colonic temperature were maximal at 30 degrees C. The results suggest that tests of beta-adrenergic responsiveness using this technique should be performed at an ambient temperature of 26 degrees C for maximal sensitivity.", "contents": "The effect of ambient temperature on beta-adrenergic responsiveness in rats. The responses of tail skin and colonic temperatures of female rats to ambient temperatures of 20, 22, 24, 26, 28, and 30 degrees C were measured. Within this range, colonic temperature was stable while tail skin temperature increased linearly with increasing ambient temperature. Administration of the beta-adrenergic agonist, d,l-isoproterenol, at 10.0, 25.0, and 62.5 micrograms/kg, sc, at each ambient temperature was accompanied by increases in tail skin and colonic temperatures that were dependent on both the dose of isoproterenol administered and the ambient temperature. The integrated responses of tail skin temperature following administration of the three doses of isoproterenol were maximal at an ambient temperature of 26 degrees C while the integrated responses of colonic temperature were maximal at 30 degrees C. The results suggest that tests of beta-adrenergic responsiveness using this technique should be performed at an ambient temperature of 26 degrees C for maximal sensitivity."}
{"id": "PMID:226257", "title": "The Syrian golden hamster: a model for the cardiomyopathy of Friedreich's ataxia.", "content": "In light of the available information on the cardiomyopathy of Friedreich's ataxia, the cardiomyopathic Syrian hamster may be an appropriate laboratory model. Cardiomyopathy in these animals is a result of calcium accumulation. We analyzed the atria and right and left ventricles from cardiomyopathic (CM) and random bred (RB) animals for calcium, magnesium, and iron concentrations at 30-40 and 60-70 days of age (age of maximum lesioning). There are no significant differences in the concentration of iron or magnesium among age-matched groups. The concentration of calcium in the left ventricles of the CM animals at 60 days old is 14 fold higher than that of RB animals. Although there is a significant difference in the concentration of calcium in the left ventricles of younger animals, it is not as pronounced as the difference in older animals. Analysis of the taurine concentration in 30-40 day old animals revealed that the CM animals show slightly higher taurine concentrations than RB in the whole heart. In 60 day old CM hamsters in the beta-adrenergic receptor density of the ventricles is unchanged. This indicates that calcium overload is not due to adrenergic supersensitivity.", "contents": "The Syrian golden hamster: a model for the cardiomyopathy of Friedreich's ataxia. In light of the available information on the cardiomyopathy of Friedreich's ataxia, the cardiomyopathic Syrian hamster may be an appropriate laboratory model. Cardiomyopathy in these animals is a result of calcium accumulation. We analyzed the atria and right and left ventricles from cardiomyopathic (CM) and random bred (RB) animals for calcium, magnesium, and iron concentrations at 30-40 and 60-70 days of age (age of maximum lesioning). There are no significant differences in the concentration of iron or magnesium among age-matched groups. The concentration of calcium in the left ventricles of the CM animals at 60 days old is 14 fold higher than that of RB animals. Although there is a significant difference in the concentration of calcium in the left ventricles of younger animals, it is not as pronounced as the difference in older animals. Analysis of the taurine concentration in 30-40 day old animals revealed that the CM animals show slightly higher taurine concentrations than RB in the whole heart. In 60 day old CM hamsters in the beta-adrenergic receptor density of the ventricles is unchanged. This indicates that calcium overload is not due to adrenergic supersensitivity."}
{"id": "PMID:226258", "title": "Brain neurotransmitter receptors in Friedreich's ataxia.", "content": "The binding of 3H-quinuclidinyl benzilate, a muscarinic cholinergic antagonist, of 3H-dihydroalprenolol, a beta adrenergic antagonist, and of 3H-flunitrazepam, a ligand which labels benzodiazepine receptors, was examined in several regions of control and Friedreich's ataxia (FA) brains. 3H-Quinuclidinyl benzilate binding appeared to increase in the inferior olivory nucleus, anterior and posterior cerebellar vermi but was unaltered in the dentate nucleus and cerebellar hemisphere of FA brain. The binding of 3H-dihydroalprenolol seemed to increase in the inferior olivary nucleus yet was not different from controls in the dentate nucleus, cerebellar hemisphere, anterior and posterior cerebellar vermi of FA brains. 3H-Flunitrazepam binding was slightly lowered in the inferior olivary and dentate nuclei but was unchanged in the other FA brain regions examined. The present study suggests possible trends in neurotransmitter receptor alterations in post-mortem brain tissue of FA patients.", "contents": "Brain neurotransmitter receptors in Friedreich's ataxia. The binding of 3H-quinuclidinyl benzilate, a muscarinic cholinergic antagonist, of 3H-dihydroalprenolol, a beta adrenergic antagonist, and of 3H-flunitrazepam, a ligand which labels benzodiazepine receptors, was examined in several regions of control and Friedreich's ataxia (FA) brains. 3H-Quinuclidinyl benzilate binding appeared to increase in the inferior olivory nucleus, anterior and posterior cerebellar vermi but was unaltered in the dentate nucleus and cerebellar hemisphere of FA brain. The binding of 3H-dihydroalprenolol seemed to increase in the inferior olivary nucleus yet was not different from controls in the dentate nucleus, cerebellar hemisphere, anterior and posterior cerebellar vermi of FA brains. 3H-Flunitrazepam binding was slightly lowered in the inferior olivary and dentate nuclei but was unchanged in the other FA brain regions examined. The present study suggests possible trends in neurotransmitter receptor alterations in post-mortem brain tissue of FA patients."}
{"id": "PMID:226259", "title": "Fatty acid profile of major lipid classes in plasma lipoproteins of patients with Friedreich's ataxia-demonstration of a low linoleic acid content most evident in the cholesterol-ester fraction.", "content": "Studies were undertaken to further characterize plasma lipids and lipoprotein abnormalities in Friedreich's ataxia. The high density lipoprotein (HDL) apo AI/AII ratio was quantitated by densitometry and found to be normal. The free to esterified cholesterol ratio in HDL was lower in Friedreich's ataxia because of a reduction in the amount of free cholesterol in this lipoprotein class. The fatty acid profile of the cholesteryl-ester (CE) fraction was markedly deficient in linoleic acid (18:2) in both total plasma and HDL. There was a compensatory increase in saturated acids. The HDL phospholipid (PL) fraction also showed a reduction in the proportion of 18:2 with a concomitant increase in stearic (18:0) and oleic acid (18:1) while the HDL triglyceride (TG) fraction showed only an increase in palmitoleic (16:1) and oleic acids. Feeding of soya lecithin rich in 18:2 failed to increase significantly the 18:2 content of HDL-CE and HDL-PL but lowered the percentage of 16:1 and 18:1 in all 3 lipid classes of HDL. Although the total plasma CE fatty acid profile was perturbed in Friedreich's Ataxia, total plasma PL and TG fatty acid patterns were unaffected. Among the plasma lipoprotein fatty acid profiles, that of the low density lipoprotein (LDL) was most affected, then that of the HDL. The very low density lipoprotein (VLDL) fatty acid composition showed an increase in 16:1 and a decrease in 18:2 which were entirely corrected by lecithin feeding. These results suggest the existence of a metabolic defect in the incorporation of 18:2 into chylomicron phospholipids within the intestinal mucosa.", "contents": "Fatty acid profile of major lipid classes in plasma lipoproteins of patients with Friedreich's ataxia-demonstration of a low linoleic acid content most evident in the cholesterol-ester fraction. Studies were undertaken to further characterize plasma lipids and lipoprotein abnormalities in Friedreich's ataxia. The high density lipoprotein (HDL) apo AI/AII ratio was quantitated by densitometry and found to be normal. The free to esterified cholesterol ratio in HDL was lower in Friedreich's ataxia because of a reduction in the amount of free cholesterol in this lipoprotein class. The fatty acid profile of the cholesteryl-ester (CE) fraction was markedly deficient in linoleic acid (18:2) in both total plasma and HDL. There was a compensatory increase in saturated acids. The HDL phospholipid (PL) fraction also showed a reduction in the proportion of 18:2 with a concomitant increase in stearic (18:0) and oleic acid (18:1) while the HDL triglyceride (TG) fraction showed only an increase in palmitoleic (16:1) and oleic acids. Feeding of soya lecithin rich in 18:2 failed to increase significantly the 18:2 content of HDL-CE and HDL-PL but lowered the percentage of 16:1 and 18:1 in all 3 lipid classes of HDL. Although the total plasma CE fatty acid profile was perturbed in Friedreich's Ataxia, total plasma PL and TG fatty acid patterns were unaffected. Among the plasma lipoprotein fatty acid profiles, that of the low density lipoprotein (LDL) was most affected, then that of the HDL. The very low density lipoprotein (VLDL) fatty acid composition showed an increase in 16:1 and a decrease in 18:2 which were entirely corrected by lecithin feeding. These results suggest the existence of a metabolic defect in the incorporation of 18:2 into chylomicron phospholipids within the intestinal mucosa."}
{"id": "PMID:226260", "title": "Evidence for an altered physical state of membrane proteins in erythrocytes in Friedreich's ataxia.", "content": "Electron spin resonance, scanning electron microscopic, and SDS-polyacrylamide gel electrophoretic studies of erythrocytes in Friedreich's ataxia have been performed. No alteration in the physical state of membrane lipids, in morphology, or in the staining profile of erythrocytes in Friedreich's ataxia could be demonstrated. An altered conformation and/or organization of proteins in erythrocyte membranes in this disorder was suggested by spin labeling studies (P less than 0.025), favoring the possibility of a generalized membrane abnormality in Friedreich's ataxia. These findings are discussed in relation to other inherited neurological diseases where similar studies have been performed.", "contents": "Evidence for an altered physical state of membrane proteins in erythrocytes in Friedreich's ataxia. Electron spin resonance, scanning electron microscopic, and SDS-polyacrylamide gel electrophoretic studies of erythrocytes in Friedreich's ataxia have been performed. No alteration in the physical state of membrane lipids, in morphology, or in the staining profile of erythrocytes in Friedreich's ataxia could be demonstrated. An altered conformation and/or organization of proteins in erythrocyte membranes in this disorder was suggested by spin labeling studies (P less than 0.025), favoring the possibility of a generalized membrane abnormality in Friedreich's ataxia. These findings are discussed in relation to other inherited neurological diseases where similar studies have been performed."}
{"id": "PMID:226261", "title": "Equine herpesvirus 1 infection in mares vaccinated with a live-virus rhinopneumonitis vaccine attenuated in cell culture.", "content": "Vaccination, in July and again in either November or December 1976, of 55 pregnant Standardbred mares with a live-virus rhinopneumonitis vaccine attenuated in cell culture failed to protect some mares from infection with equine herpesvirus 1. From 1976-12-08 to 1977-03-08, 33 mares foaled healthy foals, 16 mares foaled dead foals or live foals which died usually within 48 hours and six mares aborted. Gross and histological examinations and virus isolation studies confirmed that equine herpesvirus 1 caused 18 of the 22 neonatal deaths, stillbirths or abortions.", "contents": "Equine herpesvirus 1 infection in mares vaccinated with a live-virus rhinopneumonitis vaccine attenuated in cell culture. Vaccination, in July and again in either November or December 1976, of 55 pregnant Standardbred mares with a live-virus rhinopneumonitis vaccine attenuated in cell culture failed to protect some mares from infection with equine herpesvirus 1. From 1976-12-08 to 1977-03-08, 33 mares foaled healthy foals, 16 mares foaled dead foals or live foals which died usually within 48 hours and six mares aborted. Gross and histological examinations and virus isolation studies confirmed that equine herpesvirus 1 caused 18 of the 22 neonatal deaths, stillbirths or abortions."}
{"id": "PMID:226265", "title": "Cells transformed by temperature-sensitive mutants of avian sarcoma virus cause tumors in vivo at permissive and nonpermissive temperatures.", "content": "Chick embryo (CE) fibroblasts and normal rat kidney (NRK) cells transformed by temperature-sensitive (ts) mutants of avian sarcoma virus (NY68, LA23, LA24, LA25, LA29, LA31, GI201, GI202, GI251, GI253 induce tumors on the chorioallantoic membrane (CAM) of chick eggs at temperatures that correspond to the permissive and nonpermissive temperatures used to induce conditional expression of the \"transformed\" phenotype in these cells when cultured in vitro. Chick embryo cells infected with transformation-defective mutants of ASV (td101, td108) or RAV-50 were nontumorigenic under the same conditions, as were nontransformed CE and NRK cells. This indicates that the CAM is not an unusually susceptible substrate for cell growth and that the ability of tsASV-transformed cells to form tumors at nonpermissive temperatures reflects their true tumorigenicity. In contrast, a ts mutant chemically transformed rat liver cell line, ts-223, only formed tumors on the CAM under permissive conditions. The wild-type parent cells (W-8) of this mutant produced tumors at both permissive and nonpermissive temperatures. Direct implantation of microprobe thermometers into tumors caused by ts-ASV-transformed cells at nonpermissive temperatures confirmed that tumor formation occurred in a stable temperature environment and was not due to temperature fluctuations which might have created semi-permissive conditions for tumor growth. Cells isolated from tumors formed at nonpermissive temperatures and recultured in vitro displayed temperature-dependent hexose transport and colony formation in agar similar to the orginal parent cell inoculum. Similarly, virus recovered from tumors at nonpermissive temperatures retained the ts mutation.", "contents": "Cells transformed by temperature-sensitive mutants of avian sarcoma virus cause tumors in vivo at permissive and nonpermissive temperatures. Chick embryo (CE) fibroblasts and normal rat kidney (NRK) cells transformed by temperature-sensitive (ts) mutants of avian sarcoma virus (NY68, LA23, LA24, LA25, LA29, LA31, GI201, GI202, GI251, GI253 induce tumors on the chorioallantoic membrane (CAM) of chick eggs at temperatures that correspond to the permissive and nonpermissive temperatures used to induce conditional expression of the \"transformed\" phenotype in these cells when cultured in vitro. Chick embryo cells infected with transformation-defective mutants of ASV (td101, td108) or RAV-50 were nontumorigenic under the same conditions, as were nontransformed CE and NRK cells. This indicates that the CAM is not an unusually susceptible substrate for cell growth and that the ability of tsASV-transformed cells to form tumors at nonpermissive temperatures reflects their true tumorigenicity. In contrast, a ts mutant chemically transformed rat liver cell line, ts-223, only formed tumors on the CAM under permissive conditions. The wild-type parent cells (W-8) of this mutant produced tumors at both permissive and nonpermissive temperatures. Direct implantation of microprobe thermometers into tumors caused by ts-ASV-transformed cells at nonpermissive temperatures confirmed that tumor formation occurred in a stable temperature environment and was not due to temperature fluctuations which might have created semi-permissive conditions for tumor growth. Cells isolated from tumors formed at nonpermissive temperatures and recultured in vitro displayed temperature-dependent hexose transport and colony formation in agar similar to the orginal parent cell inoculum. Similarly, virus recovered from tumors at nonpermissive temperatures retained the ts mutation."}
{"id": "PMID:226267", "title": "Expression of the autonomous parvovirus H1 genome: evidence for a single transcriptional unit and multiple spliced polyadenylated transcripts.", "content": "We identified viral transcripts in parvovirus H1-infected rodent cells using the S1 nuclease mapping technique of Berk and Sharp (1977, 1978). The most abundant viral transcript, present in both nucleus and cytoplasm, is approximately 2.8 kb long and represents about 56% of the viral genome. Less abundant viral transcripts of 3.0, 1.45 and 1.30 kb, and possibly other minor viral transcripts, are also detected in nuclear and cytoplasmic fractions. In contrast, a prominent 4.7 kb viral transcript which corresponds to 95% of the viral DNA is found only in the nucleus; this finding suggests that the parvovirus genome may function as a single transcription unit. Virus-infected cells pretreated with cycloheximide accumulate all these viral transcripts. Analyses of RNA-DNA hybrids (isolated from neutral agarose gels) by electrophoresis on alkaline agarose gels indicate that the 4.7, 3.0 and 2.8 kb viral transcripts are \"spliced\" RNAs. The nuclear-specific 4.7 kb transcript appears to be encoded by two noncontiguous DNA segments of 2.2 and 2.6 kb. The 3.0 and 2.8 kb transcripts are apparently encoded by.a 2.6 kb segment of DNA and one or more much smaller noncontiguous DNA segments, one of which is approximately 170 nucleotides long.", "contents": "Expression of the autonomous parvovirus H1 genome: evidence for a single transcriptional unit and multiple spliced polyadenylated transcripts. We identified viral transcripts in parvovirus H1-infected rodent cells using the S1 nuclease mapping technique of Berk and Sharp (1977, 1978). The most abundant viral transcript, present in both nucleus and cytoplasm, is approximately 2.8 kb long and represents about 56% of the viral genome. Less abundant viral transcripts of 3.0, 1.45 and 1.30 kb, and possibly other minor viral transcripts, are also detected in nuclear and cytoplasmic fractions. In contrast, a prominent 4.7 kb viral transcript which corresponds to 95% of the viral DNA is found only in the nucleus; this finding suggests that the parvovirus genome may function as a single transcription unit. Virus-infected cells pretreated with cycloheximide accumulate all these viral transcripts. Analyses of RNA-DNA hybrids (isolated from neutral agarose gels) by electrophoresis on alkaline agarose gels indicate that the 4.7, 3.0 and 2.8 kb viral transcripts are \"spliced\" RNAs. The nuclear-specific 4.7 kb transcript appears to be encoded by two noncontiguous DNA segments of 2.2 and 2.6 kb. The 3.0 and 2.8 kb transcripts are apparently encoded by.a 2.6 kb segment of DNA and one or more much smaller noncontiguous DNA segments, one of which is approximately 170 nucleotides long."}
{"id": "PMID:226268", "title": "Defective interfering particles modulate VSV infection of dissociated neuron cultures.", "content": "Infection of dissociated neuron cultures of mice with VSV and its defective particle DI-T was studied using fluorescent light microscopy as well as transmission and scanning electron microscopy. When cultures are infected with wild virus, VSV replicates selectively in neurons, producing cell death within 24-48 hr. Sensory and immature neurons express viral antigen most rapidly. Viral antigen and viral budding sites are detected along the neuron soma and dendrites. When large amounts of DI-T particles are added to the wild virus inoculum, viral growth is completely suppressed in mature neurons, the cell killing effects of VSV are considerably delayed and co-infected cultures survive for 5-16 days. Viral antigen accumulates in cytoplasmic inclusions and on the membrane of neuron cell somas and dendrites in the virtual absence of viral assembly. Identical modulation of VSV infection in mature neuron cultures is obtained when DI-T particles are added before or after the wild virus, but ultraviolet inactivation of DIs completely abolishes their protective effect. Immature neurons or Vero cells cannot be protected from acute cytopathic changes by an equivalent amount of DI particles. Thus DIs interfere with replication and assembly of the wild virus and attenuate cell killing effects in mature neurons in vitro.", "contents": "Defective interfering particles modulate VSV infection of dissociated neuron cultures. Infection of dissociated neuron cultures of mice with VSV and its defective particle DI-T was studied using fluorescent light microscopy as well as transmission and scanning electron microscopy. When cultures are infected with wild virus, VSV replicates selectively in neurons, producing cell death within 24-48 hr. Sensory and immature neurons express viral antigen most rapidly. Viral antigen and viral budding sites are detected along the neuron soma and dendrites. When large amounts of DI-T particles are added to the wild virus inoculum, viral growth is completely suppressed in mature neurons, the cell killing effects of VSV are considerably delayed and co-infected cultures survive for 5-16 days. Viral antigen accumulates in cytoplasmic inclusions and on the membrane of neuron cell somas and dendrites in the virtual absence of viral assembly. Identical modulation of VSV infection in mature neuron cultures is obtained when DI-T particles are added before or after the wild virus, but ultraviolet inactivation of DIs completely abolishes their protective effect. Immature neurons or Vero cells cannot be protected from acute cytopathic changes by an equivalent amount of DI particles. Thus DIs interfere with replication and assembly of the wild virus and attenuate cell killing effects in mature neurons in vitro."}
{"id": "PMID:226281", "title": "[Effects of cyclic AMP treatment on the migration of primordial germ cells in the embryo of Xenopus laevis].", "content": "After a treatment of early embryos by AMPc, only 40% of the primordial germ cells are found in the gonads; the others are found in the dorsal mesentery and especially in the intestinal wall.", "contents": "[Effects of cyclic AMP treatment on the migration of primordial germ cells in the embryo of Xenopus laevis]. After a treatment of early embryos by AMPc, only 40% of the primordial germ cells are found in the gonads; the others are found in the dorsal mesentery and especially in the intestinal wall."}
{"id": "PMID:226282", "title": "[Histochemical localization of lactate dehydrogenase (LDH) during cartilaginous cell differentiation in pleurodeles (Pleurodeles waltlii Michah].", "content": "As revealed in chondrogenetic cells the LDH activity that is very low during cellular migration, suddenly increases at the time of cytodifferentiation and reaches a peak at the onset of the first chondrocyte differentiation. A relationship is likely to exist between this increase in LDH-activity, chondroitin-sulfate synthesis and NAD metabolism.", "contents": "[Histochemical localization of lactate dehydrogenase (LDH) during cartilaginous cell differentiation in pleurodeles (Pleurodeles waltlii Michah]. As revealed in chondrogenetic cells the LDH activity that is very low during cellular migration, suddenly increases at the time of cytodifferentiation and reaches a peak at the onset of the first chondrocyte differentiation. A relationship is likely to exist between this increase in LDH-activity, chondroitin-sulfate synthesis and NAD metabolism."}
{"id": "PMID:226283", "title": "[Suppressor effect induced by sodium periodate on the antibody response of mouse splenic cells in vitro : inhibition of this effect by sodium borohydride].", "content": "Mild oxidation of mouse spleen cells by sodium periodate induces blastogenesis. Concomitantly, the in vitro response of these cells to sheep red blood cells is inhibited. Exposure of spleen cells to sodium borohydride following periodate treatment reduces blastogenesis and restores the immune response.", "contents": "[Suppressor effect induced by sodium periodate on the antibody response of mouse splenic cells in vitro : inhibition of this effect by sodium borohydride]. Mild oxidation of mouse spleen cells by sodium periodate induces blastogenesis. Concomitantly, the in vitro response of these cells to sheep red blood cells is inhibited. Exposure of spleen cells to sodium borohydride following periodate treatment reduces blastogenesis and restores the immune response."}
{"id": "PMID:226284", "title": "Visualization of the distance between perfusion and anoxia along an ischemic border.", "content": "The distance between perfusion and anoxia was measured on the border of an experimental ischemic area in the rabbit heart. Reduced nicotinamide adenine dinucleotide (NADH) fluorescence photography was used to detect myocardial anoxia. Fluorescein angiography marked areas of myocardial perfusion. The hearts were isolated, perfused with a hemoglobin-free solution and performed no external work. In all hearts there was a narrow band between areas of perfusion and anoxia that measured 329 +/- 42 mu (mean +/- SD). The transition from minimal to full NADH fluorescence was abrupt, less than 80 mu. We conclude that the normoxic/anoxic transition is sharp, and the gap between perfusion and anoxia is narrow along an ischemic border in the isolated heart performing no external work. These data suggest that in the vivo working heart the gap between perfusion and anoxia would be even narrower.", "contents": "Visualization of the distance between perfusion and anoxia along an ischemic border. The distance between perfusion and anoxia was measured on the border of an experimental ischemic area in the rabbit heart. Reduced nicotinamide adenine dinucleotide (NADH) fluorescence photography was used to detect myocardial anoxia. Fluorescein angiography marked areas of myocardial perfusion. The hearts were isolated, perfused with a hemoglobin-free solution and performed no external work. In all hearts there was a narrow band between areas of perfusion and anoxia that measured 329 +/- 42 mu (mean +/- SD). The transition from minimal to full NADH fluorescence was abrupt, less than 80 mu. We conclude that the normoxic/anoxic transition is sharp, and the gap between perfusion and anoxia is narrow along an ischemic border in the isolated heart performing no external work. These data suggest that in the vivo working heart the gap between perfusion and anoxia would be even narrower."}
{"id": "PMID:226285", "title": "Evaluation of a rapid, sensitive and specific assay for the determination of collagenolytic activity in biological samples.", "content": "Several methods for the determination of collagenolytic activity were compared from the point of view of sensitivity, selectivity, simplicity and practical value for large numbers of biological samples. A labelled collagen substrate was prepared using [3H]acetic anhydride. The specificity of the assay as well as conditions allowing an optimum detection limit were investigated. The influence of low temperatures, lyophilisation and salt concentration on Clostridium histolyticum collagenase have been investigated.", "contents": "Evaluation of a rapid, sensitive and specific assay for the determination of collagenolytic activity in biological samples. Several methods for the determination of collagenolytic activity were compared from the point of view of sensitivity, selectivity, simplicity and practical value for large numbers of biological samples. A labelled collagen substrate was prepared using [3H]acetic anhydride. The specificity of the assay as well as conditions allowing an optimum detection limit were investigated. The influence of low temperatures, lyophilisation and salt concentration on Clostridium histolyticum collagenase have been investigated."}
{"id": "PMID:226286", "title": "Serum high density lipoprotein cholesterol determination: a simple modification.", "content": "A simple modification to the method of Burnstein et al. (Burnstein, M., Scholnick, H.R. and Morfin, R. (1970) J. Lip. Res. 11, 583) [1] for the measurement of serum high-density lipoprotein (HDL) cholesterol concentrations is reported. The modification obviates the need for a refrigerated centrifuge and makes the method suitable for routine use in almost any laboratory. Good correlation was obtained for values in 80 healthy adults using the method as originally described by Burnstein et al. [1] and then with the modification. The presented method was linear and precise and the study showed that it was not necessary to fast before giving a blood sample for the assay. It was found that HDL cholesterols were higher in women than in men, but did not change significantly with age in either group.", "contents": "Serum high density lipoprotein cholesterol determination: a simple modification. A simple modification to the method of Burnstein et al. (Burnstein, M., Scholnick, H.R. and Morfin, R. (1970) J. Lip. Res. 11, 583) [1] for the measurement of serum high-density lipoprotein (HDL) cholesterol concentrations is reported. The modification obviates the need for a refrigerated centrifuge and makes the method suitable for routine use in almost any laboratory. Good correlation was obtained for values in 80 healthy adults using the method as originally described by Burnstein et al. [1] and then with the modification. The presented method was linear and precise and the study showed that it was not necessary to fast before giving a blood sample for the assay. It was found that HDL cholesterols were higher in women than in men, but did not change significantly with age in either group."}
{"id": "PMID:226287", "title": "[A simple micromethod for sphingomyelinase determination (author's transl)].", "content": "A rapid and sensitive micromethod for routine determination of sphingomyelinase activity of leukocytes, fibroblasts and hair roots is described. This method makes use of the natural radioactive substrate of the enzyme. The product of the reaction is isolated by direct application of the incubation mixture on silica gel plates followed by ascending chromatography. The sensitivity of the method allows sphingomyelinase determination in less than 0.5 microgram of fibroblast proteins.", "contents": "[A simple micromethod for sphingomyelinase determination (author's transl)]. A rapid and sensitive micromethod for routine determination of sphingomyelinase activity of leukocytes, fibroblasts and hair roots is described. This method makes use of the natural radioactive substrate of the enzyme. The product of the reaction is isolated by direct application of the incubation mixture on silica gel plates followed by ascending chromatography. The sensitivity of the method allows sphingomyelinase determination in less than 0.5 microgram of fibroblast proteins."}
{"id": "PMID:226288", "title": "Combined hyperlipidemia and hypertriglyceridemia in renal allograft recipients. Comparison with non-renal combined hyperlipidemic or hypertriglyceridemic patients and normal subjects.", "content": "In order to investigate the degree of similarity between renal transplant and non-renal combined hyperlipidemic and hypertriglyceridemic patients, serum and lipoprotein lipid compositions were compared in transplant and non-renal combined hyperlipidemic and in transplant and non-renal hypertriglyceridemic patients, and normal subjects. Although certain similarities were demonstrated, combined hyperlipidemia in transplants differed from that in non-renal patients in a number of respects: (1) LDL-triglyceride levels were increased to a greater extent in transplant than in non-renal patients in females, while LDL-phospholipid was elevated in male transplants only; (2) HDL-cholesterol levels were raised in transplants relative to non-renal patients in females, and relative to both non-renal patients and normal subjects in males; (3) a number of differences in lipoprotein-lipid ratios between transplant and non-renal patients were demonstrated for all three lipoprotein fractions. In hypertriglyceridemia, changes in lipoprotein-lipid levels were similar in transplant and non-renal patients with the exception of HDL-cholesterol levels, which were decreased in non-renal patients only. Furthermore, the ratio of esterified to free cholesterol in LDL and HDL was decreased in non-renal but not in transplant patients. The data presented demonstrate that, despite certain similarities, a number of the lipoprotein-lipid changes observed in transplant combined hyperlipidemia and in transplant hypertriglyceridemia differ from those observed in non-renal patients with similarly elevated serum lipids.", "contents": "Combined hyperlipidemia and hypertriglyceridemia in renal allograft recipients. Comparison with non-renal combined hyperlipidemic or hypertriglyceridemic patients and normal subjects. In order to investigate the degree of similarity between renal transplant and non-renal combined hyperlipidemic and hypertriglyceridemic patients, serum and lipoprotein lipid compositions were compared in transplant and non-renal combined hyperlipidemic and in transplant and non-renal hypertriglyceridemic patients, and normal subjects. Although certain similarities were demonstrated, combined hyperlipidemia in transplants differed from that in non-renal patients in a number of respects: (1) LDL-triglyceride levels were increased to a greater extent in transplant than in non-renal patients in females, while LDL-phospholipid was elevated in male transplants only; (2) HDL-cholesterol levels were raised in transplants relative to non-renal patients in females, and relative to both non-renal patients and normal subjects in males; (3) a number of differences in lipoprotein-lipid ratios between transplant and non-renal patients were demonstrated for all three lipoprotein fractions. In hypertriglyceridemia, changes in lipoprotein-lipid levels were similar in transplant and non-renal patients with the exception of HDL-cholesterol levels, which were decreased in non-renal patients only. Furthermore, the ratio of esterified to free cholesterol in LDL and HDL was decreased in non-renal but not in transplant patients. The data presented demonstrate that, despite certain similarities, a number of the lipoprotein-lipid changes observed in transplant combined hyperlipidemia and in transplant hypertriglyceridemia differ from those observed in non-renal patients with similarly elevated serum lipids."}
{"id": "PMID:226289", "title": "Electroimmunoassay of a subunit protein in a macromolecular complex (apolipoprotein B in human plasma very low density lipoprotein); implications for other electroimmunoassay systems.", "content": "With an electroimmunoassay (\"rocket\") system for the apolipoprotein B component of the plasma very low density lipoprotein complex we obtained results which were similar to those obtained by a colorimetric tetramethylurea extraction method. Results were up to twice as high as those using radioimmunoassay. Low density lipoprotein containing apolipoprotein B as the only demonstrable protein component was used as the standard for these assays. This protein produced larger and higher rockets at pH 8.6 when the negative particle charge was increased by maleylation. The very low density lipoprotein complex has a higher negative charge at pH 8.6 than low density lipoprotein. These findings suggest that some apolipoprotein B in vary low density lipoprotein is not \"recognised\" by anti-apolipoprotein B antibodies, hence radioimmunoassay results are lower than those obtained with the tetramethylurea extraction method. The higher negative charge on very low density lipoprotein particles (compared with low density lipoprotein), as a factor tending to increase rocket area and height, is counterbalanced by reduced recognition by antiapolipoprotein B antibodies. The net result of these opposing tendencies is that the rocket electroimmunoassay of apolipoprotein B in very low density lipoprotein fortuitously gives valid results, under the specified assay conditions. We conclude that electroimmunoassays of complex proteins are not necessarily valid if protein subunits are used for standards. This has implications for the electroimmunoassay of other apolipoproteins.", "contents": "Electroimmunoassay of a subunit protein in a macromolecular complex (apolipoprotein B in human plasma very low density lipoprotein); implications for other electroimmunoassay systems. With an electroimmunoassay (\"rocket\") system for the apolipoprotein B component of the plasma very low density lipoprotein complex we obtained results which were similar to those obtained by a colorimetric tetramethylurea extraction method. Results were up to twice as high as those using radioimmunoassay. Low density lipoprotein containing apolipoprotein B as the only demonstrable protein component was used as the standard for these assays. This protein produced larger and higher rockets at pH 8.6 when the negative particle charge was increased by maleylation. The very low density lipoprotein complex has a higher negative charge at pH 8.6 than low density lipoprotein. These findings suggest that some apolipoprotein B in vary low density lipoprotein is not \"recognised\" by anti-apolipoprotein B antibodies, hence radioimmunoassay results are lower than those obtained with the tetramethylurea extraction method. The higher negative charge on very low density lipoprotein particles (compared with low density lipoprotein), as a factor tending to increase rocket area and height, is counterbalanced by reduced recognition by antiapolipoprotein B antibodies. The net result of these opposing tendencies is that the rocket electroimmunoassay of apolipoprotein B in very low density lipoprotein fortuitously gives valid results, under the specified assay conditions. We conclude that electroimmunoassays of complex proteins are not necessarily valid if protein subunits are used for standards. This has implications for the electroimmunoassay of other apolipoproteins."}
{"id": "PMID:226290", "title": "Departure from ideality in saturation binding assays.", "content": "In this paper we show that the measurement of cyclic AMP by a protein saturation assay deviates from ideality due to the presence of two classes of binding sites. An equation was derived which completely describes saturation assays and the effects on these of varying each of the component parameters was measured. The relevance of these findings to other protein saturation assays is discussed.", "contents": "Departure from ideality in saturation binding assays. In this paper we show that the measurement of cyclic AMP by a protein saturation assay deviates from ideality due to the presence of two classes of binding sites. An equation was derived which completely describes saturation assays and the effects on these of varying each of the component parameters was measured. The relevance of these findings to other protein saturation assays is discussed."}
{"id": "PMID:226298", "title": "Oculodento-osseous dysplasia: heterogeneity or variable expression?", "content": "Oculodento-osseous dysplasia (ODOD) has been recognised in three South African patients from two kindreds of Dutch descent. Their ocular, nasal, dental and digital stigmata resembled those of previously reported cases, but their cranial hyperostosis and mandibular overgrowth were of much greater degree. In addition, the two survivors had serious neurological complications consequent upon spinal cord compression at the base of the skull and calcification of the basal ganglia. Two of the patients were the product of marriages between a pair of brothers and a pair of sisters, who were themselves clinically normal. This situation is best explained by autosomal recessive inheritance. As ODOD is usually transmitted as an autosomal dominant, and in view of the unusual severity of the manifestations in our patients, it is possible that the condition is heterogeneous and that they had a distinct autosomal recessive form of the disorder. The presence of minimal stigmata in the mother and two prior generations of our third patient could be equally well interpreted as representing great variation in phenotypic expression of a single dominant gene or manifestation in a heterozygote for a recessive gene.", "contents": "Oculodento-osseous dysplasia: heterogeneity or variable expression? Oculodento-osseous dysplasia (ODOD) has been recognised in three South African patients from two kindreds of Dutch descent. Their ocular, nasal, dental and digital stigmata resembled those of previously reported cases, but their cranial hyperostosis and mandibular overgrowth were of much greater degree. In addition, the two survivors had serious neurological complications consequent upon spinal cord compression at the base of the skull and calcification of the basal ganglia. Two of the patients were the product of marriages between a pair of brothers and a pair of sisters, who were themselves clinically normal. This situation is best explained by autosomal recessive inheritance. As ODOD is usually transmitted as an autosomal dominant, and in view of the unusual severity of the manifestations in our patients, it is possible that the condition is heterogeneous and that they had a distinct autosomal recessive form of the disorder. The presence of minimal stigmata in the mother and two prior generations of our third patient could be equally well interpreted as representing great variation in phenotypic expression of a single dominant gene or manifestation in a heterozygote for a recessive gene."}
{"id": "PMID:226300", "title": "An approach to the routine estimation of circulating carcinoembryonic antigen immune complexes in patients with carcinomata of the gastrointestinal tract.", "content": "The carcinoembryonic antigen (CEA) distribution obtained after fractionation of thirty sera of patients with gastrointestinal tumours by gel filtration in Sephadex G200 was compared with that resulting from extraction of the sera with perchloric acid. In all cases gel filtration yielded a fraction of free CEA and in twenty-three cases an additional fraction of CEA immune complexes. The amounts of free CEA corresponded fairly well to the fractions of CEA which could be extracted by perchloric acid. The CEA content of the fraction containing CEA immune complexes was comparable to the CEA content of the perchloric acid precipitates. The presence of CEA immune complexes in the perchloric acid precipitates could be demonstrated by gel filtration under dissociating andnon-dissociating conditions and after pre-incubation with 125I-CEA by radioimmuno-double-diffusion using monospecific rabbit antisera against human IgM and IgG.", "contents": "An approach to the routine estimation of circulating carcinoembryonic antigen immune complexes in patients with carcinomata of the gastrointestinal tract. The carcinoembryonic antigen (CEA) distribution obtained after fractionation of thirty sera of patients with gastrointestinal tumours by gel filtration in Sephadex G200 was compared with that resulting from extraction of the sera with perchloric acid. In all cases gel filtration yielded a fraction of free CEA and in twenty-three cases an additional fraction of CEA immune complexes. The amounts of free CEA corresponded fairly well to the fractions of CEA which could be extracted by perchloric acid. The CEA content of the fraction containing CEA immune complexes was comparable to the CEA content of the perchloric acid precipitates. The presence of CEA immune complexes in the perchloric acid precipitates could be demonstrated by gel filtration under dissociating andnon-dissociating conditions and after pre-incubation with 125I-CEA by radioimmuno-double-diffusion using monospecific rabbit antisera against human IgM and IgG."}
{"id": "PMID:226305", "title": "Effect of furosemide on plasma concentration and beta-blockade by propranolol.", "content": "Although propranolol and furosemide are used together for hypertension, the effects of furosemide on plasma levels and beta-blocking action of propranolol are not known. Ten healthy subjects received propranolol 40 mg orally; the mean plasma propranolol levels in 60, 90, 180, and 300 min were 85 +/- 16, 90 +/- 7, 82 +/- 8, and 58 +/- 8 ng/ml. Propranolol was then given together with furosemide (25 mg orally) and the propranolol blood level was measured. Mean propranolol plasma levels were 106 +/- 11 ng/ml at 60 min, 120 +/- 12 ng/ml at 90 min (p less than 0.01), 102 +/- 8 ng/ml at 180 min (p less than 0.05), and 78 +/- 8 ng/ml at 300 min (p less than 0.01). Six additional subjects were given an infusion of 1 microgram/min isoproterenol increased by 0.5 microgram/min every 2 min until the heart rate rose by 25% after oral administration of furosemide 25 mg. This procedure was repeated after propranolol (40 mg orally) and propranolol with furosemide (25 mg orally). The amount of isoproterenol which raised the heart rate by 25% was 2.6 +/- 0.3 micrograms after furosemide alone and 17.7 +/- 2 micrograms after propranolol (p less than 0.01). After propranolol with furosemide the dose of isoproterenol required to elevate heart rate by 25% was 109 +/- 15 micrograms (p less than 0.001).", "contents": "Effect of furosemide on plasma concentration and beta-blockade by propranolol. Although propranolol and furosemide are used together for hypertension, the effects of furosemide on plasma levels and beta-blocking action of propranolol are not known. Ten healthy subjects received propranolol 40 mg orally; the mean plasma propranolol levels in 60, 90, 180, and 300 min were 85 +/- 16, 90 +/- 7, 82 +/- 8, and 58 +/- 8 ng/ml. Propranolol was then given together with furosemide (25 mg orally) and the propranolol blood level was measured. Mean propranolol plasma levels were 106 +/- 11 ng/ml at 60 min, 120 +/- 12 ng/ml at 90 min (p less than 0.01), 102 +/- 8 ng/ml at 180 min (p less than 0.05), and 78 +/- 8 ng/ml at 300 min (p less than 0.01). Six additional subjects were given an infusion of 1 microgram/min isoproterenol increased by 0.5 microgram/min every 2 min until the heart rate rose by 25% after oral administration of furosemide 25 mg. This procedure was repeated after propranolol (40 mg orally) and propranolol with furosemide (25 mg orally). The amount of isoproterenol which raised the heart rate by 25% was 2.6 +/- 0.3 micrograms after furosemide alone and 17.7 +/- 2 micrograms after propranolol (p less than 0.01). After propranolol with furosemide the dose of isoproterenol required to elevate heart rate by 25% was 109 +/- 15 micrograms (p less than 0.001)."}
{"id": "PMID:226306", "title": "Efficacy of estradiol vaginal cream in postmenopausal women.", "content": "In a double-blind parallel study daily intravaginal administration of conjugated estrogen cream and estradiol cream for 14 days relieved vasomotor and vaginal postmenopausal symptoms in 29 postmenopausal women. By day 14, therapy with the estradiol vaginal cream resulted in plasma estrone and estradiol levels closer to those in premenopausal women than therapy with the conjugated estrogen cream. The extent of improvement and final estradiol plasma levels in the estradiol vaginal-cream group correlated. There was no correlation with severity of symptoms or estradiol plasma level at baseline. The metabolism of the conjugated estrogen cream might account for absence of correlation between improvement and final estradiol plasma levels in the conjugated vaginal-cream group.", "contents": "Efficacy of estradiol vaginal cream in postmenopausal women. In a double-blind parallel study daily intravaginal administration of conjugated estrogen cream and estradiol cream for 14 days relieved vasomotor and vaginal postmenopausal symptoms in 29 postmenopausal women. By day 14, therapy with the estradiol vaginal cream resulted in plasma estrone and estradiol levels closer to those in premenopausal women than therapy with the conjugated estrogen cream. The extent of improvement and final estradiol plasma levels in the estradiol vaginal-cream group correlated. There was no correlation with severity of symptoms or estradiol plasma level at baseline. The metabolism of the conjugated estrogen cream might account for absence of correlation between improvement and final estradiol plasma levels in the conjugated vaginal-cream group."}
{"id": "PMID:226301", "title": "beta 2-Adrenoceptors in rat liver microcirculation.", "content": "1. Rat liver sinusoids were observed by a microscopic in vivo transillumination method. The diameter of liver sinusoids and intrasinusoid erythrocyte flow velocities were measured quantitatively by a close-circuit television technique. 2. Both isoprenaline and the selective beta 2-adrenoceptor agonist terbutaline produced a concentration-dependent dilatation of liver sinusoids and slowed erythrocyte flow velocity. The effects of isoprenaline and terbutaline were antagonized by propranolol but not by the selective beta 1-adrenoceptor antagonist atenolol. Propranolol alone produced constriction of the liver sinusoids and increased erythrocyte flow velocity; these effects were not produced by atenolol. 3. The percentage dilatations produced by isoprenaline alone, isoprenaline in the presence of phenoxybenzamine and isoprenaline in the presence of phenylephrine-induced constriction were similar. 4. It is proposed that the beta-adrenoceptors in liver sinusoids are of the beta 2-type, and their physiological role was to counteract constrictor responses produced by alpha-adrenoceptor activity.", "contents": "beta 2-Adrenoceptors in rat liver microcirculation. 1. Rat liver sinusoids were observed by a microscopic in vivo transillumination method. The diameter of liver sinusoids and intrasinusoid erythrocyte flow velocities were measured quantitatively by a close-circuit television technique. 2. Both isoprenaline and the selective beta 2-adrenoceptor agonist terbutaline produced a concentration-dependent dilatation of liver sinusoids and slowed erythrocyte flow velocity. The effects of isoprenaline and terbutaline were antagonized by propranolol but not by the selective beta 1-adrenoceptor antagonist atenolol. Propranolol alone produced constriction of the liver sinusoids and increased erythrocyte flow velocity; these effects were not produced by atenolol. 3. The percentage dilatations produced by isoprenaline alone, isoprenaline in the presence of phenoxybenzamine and isoprenaline in the presence of phenylephrine-induced constriction were similar. 4. It is proposed that the beta-adrenoceptors in liver sinusoids are of the beta 2-type, and their physiological role was to counteract constrictor responses produced by alpha-adrenoceptor activity."}
{"id": "PMID:226326", "title": "An analysis of distance variables that affect aftercare attendance.", "content": "Recent reserach has examined variables related to attendance of aftercare services because of the correlation between aftercare and posthospitalization treatment success. The present study, which examined aftercare attendance for 40 randomyl selected subjects following discharge from an inpatient alcohol treatment program, extends the list of variables found to influence attendance. A multiple-regression analysis of subject demographic variables and variables of a more programmatic nature found that distance variables (e.g., number of miles to an aftercare agency) significantly influenced aftercare attendance. The results are discussed with respect to aftercare program decisions.", "contents": "An analysis of distance variables that affect aftercare attendance. Recent reserach has examined variables related to attendance of aftercare services because of the correlation between aftercare and posthospitalization treatment success. The present study, which examined aftercare attendance for 40 randomyl selected subjects following discharge from an inpatient alcohol treatment program, extends the list of variables found to influence attendance. A multiple-regression analysis of subject demographic variables and variables of a more programmatic nature found that distance variables (e.g., number of miles to an aftercare agency) significantly influenced aftercare attendance. The results are discussed with respect to aftercare program decisions."}
{"id": "PMID:226327", "title": "Simulation of coupling between chemical reactions and ion transport in brown adipose tissue using network thermodynamics.", "content": "Several cellular events associated with energy turnover in the mitochondria and at the Na+/K+ plasma membrane pump have been formulated in terms of network thermodynamics. The calorigenic role of the Na+/K+ pump is examined in terms of the relationship between the movement of sodium and potassium ions and the chemical reactions involved. In addition, attention is centered on the potential thermogenic role of three mitochondrial pathways involving proton fluxes--namely, one in which protons are transported from the matrix to the intermembrane space; a second in which protons are transferred back into the matrix in conjunction with the synthesis of ATP; and a third wherein protons re-enter the matrix without being coupled to any chemical reaction. (This latter pathway has been delineated by studies on isolated mitochondria and may be unique to brown fat.) At both sites (plasma membrane and mitochondria) the conversion of chemical energy to heat is considered.", "contents": "Simulation of coupling between chemical reactions and ion transport in brown adipose tissue using network thermodynamics. Several cellular events associated with energy turnover in the mitochondria and at the Na+/K+ plasma membrane pump have been formulated in terms of network thermodynamics. The calorigenic role of the Na+/K+ pump is examined in terms of the relationship between the movement of sodium and potassium ions and the chemical reactions involved. In addition, attention is centered on the potential thermogenic role of three mitochondrial pathways involving proton fluxes--namely, one in which protons are transported from the matrix to the intermembrane space; a second in which protons are transferred back into the matrix in conjunction with the synthesis of ATP; and a third wherein protons re-enter the matrix without being coupled to any chemical reaction. (This latter pathway has been delineated by studies on isolated mitochondria and may be unique to brown fat.) At both sites (plasma membrane and mitochondria) the conversion of chemical energy to heat is considered."}
{"id": "PMID:226328", "title": "Characterization of increased synthesis of acute phase proteins from plasma concentration measurements: a system analysis of the ideal situation with use of computer simulation.", "content": "A method for characterizing the secretion of acute phase proteins in vivo from serial plasma concentration measurements is presented. By using a simple two-compartment model it was found that descriptive parameters could be derived from the time course of the increased plasma concentration of the protein. It was assumed that the secretion of an acute phase protein is adequately described by: (i) the start time t1; (ii) the end time t2; (iii) the magnitude of increased flux of the protein from synthetic sites to the extracellular space, described by a turnover index, S. The influence of sampling interval and analytical precision on the reliability of the estimated parameter values was investigated in the ideal situation by using computer simulation. It was found that informative estimates of the secretion rate of an acute phase protein could be obtained provided a fairly high analytical precision with a coefficient of variation less than or equal to 0.01 and using a sampling interval between 0.5--2 h.", "contents": "Characterization of increased synthesis of acute phase proteins from plasma concentration measurements: a system analysis of the ideal situation with use of computer simulation. A method for characterizing the secretion of acute phase proteins in vivo from serial plasma concentration measurements is presented. By using a simple two-compartment model it was found that descriptive parameters could be derived from the time course of the increased plasma concentration of the protein. It was assumed that the secretion of an acute phase protein is adequately described by: (i) the start time t1; (ii) the end time t2; (iii) the magnitude of increased flux of the protein from synthetic sites to the extracellular space, described by a turnover index, S. The influence of sampling interval and analytical precision on the reliability of the estimated parameter values was investigated in the ideal situation by using computer simulation. It was found that informative estimates of the secretion rate of an acute phase protein could be obtained provided a fairly high analytical precision with a coefficient of variation less than or equal to 0.01 and using a sampling interval between 0.5--2 h."}
{"id": "PMID:226329", "title": "The effect of N-(methoxy polyethylene glycol) rho-hydroxymercuribenzamide, a polymeric sulfhydryl group reagent, on spermatozoan motility.", "content": "The water-soluble, polymeric sulfhydryl group reagent N-(methoxypolyethylene glycol) rho-hydroxymercuribenzamide (Mw 5000) inhibited the motility of human spermatozoa. Its activity profile was very similar to that of rho-hydroxymercuribenzene sulfonate, a charged sulfhydryl group reagent that is a very poor membrane penetrant. These results suggest that functional sulfhydryl groups of the spermatozoan membrane are easily accessible and externally oriented on the membrane surface.", "contents": "The effect of N-(methoxy polyethylene glycol) rho-hydroxymercuribenzamide, a polymeric sulfhydryl group reagent, on spermatozoan motility. The water-soluble, polymeric sulfhydryl group reagent N-(methoxypolyethylene glycol) rho-hydroxymercuribenzamide (Mw 5000) inhibited the motility of human spermatozoa. Its activity profile was very similar to that of rho-hydroxymercuribenzene sulfonate, a charged sulfhydryl group reagent that is a very poor membrane penetrant. These results suggest that functional sulfhydryl groups of the spermatozoan membrane are easily accessible and externally oriented on the membrane surface."}
{"id": "PMID:226338", "title": "Effects of prazosin and phentolamine on cardiac presynaptic alpha-adrenoceptors in the cat, dog and rat.", "content": "In cats, dogs and rats, clonidine (20.0 microgram/Kg, i.v.) reduced the sustained tachycardia evoked by a continuous electrical stimulation of cardiac sympathetic nerve fibres. This effect of clonidine resulting from stimulation of cardiac presynaptic alpha-adrenoceptors could be completely antagonized by phentolamine and prazosin in the dog and the cat, whereas in the rat, prazosin, unlike phentolamine, failed to effectively inhibit the clonidine induced reduction in heart rate. The calculated doses of phentolamine and prazosin needed to produce a 50% antagonism were of similar magnitude in the dog, but in the cat prazosin was about three times less potent than phentolamine. As opposed to clonidine, LD 3098, a potent vascular postsynaptic alpha-adrenoceptor stimulating imidazoline, and phenylephrine (20.0 microgram/Kg, i.v.) did not significantly alter the sympathetic tachycardia in the pithed rat and the spinal dog. These results indicate that compounds stimulating postsynaptic alpha-adrenoceptors may be inactive as agonists of cardiac presynaptic alpha-adrenoceptors within the same animal species. Furthermore, a compound showing selective activity as an antagonist of vascular alpha-adrenoceptors in one species may not necessarily exert the same selective effects in other animals as demonstrated here for prazosin.", "contents": "Effects of prazosin and phentolamine on cardiac presynaptic alpha-adrenoceptors in the cat, dog and rat. In cats, dogs and rats, clonidine (20.0 microgram/Kg, i.v.) reduced the sustained tachycardia evoked by a continuous electrical stimulation of cardiac sympathetic nerve fibres. This effect of clonidine resulting from stimulation of cardiac presynaptic alpha-adrenoceptors could be completely antagonized by phentolamine and prazosin in the dog and the cat, whereas in the rat, prazosin, unlike phentolamine, failed to effectively inhibit the clonidine induced reduction in heart rate. The calculated doses of phentolamine and prazosin needed to produce a 50% antagonism were of similar magnitude in the dog, but in the cat prazosin was about three times less potent than phentolamine. As opposed to clonidine, LD 3098, a potent vascular postsynaptic alpha-adrenoceptor stimulating imidazoline, and phenylephrine (20.0 microgram/Kg, i.v.) did not significantly alter the sympathetic tachycardia in the pithed rat and the spinal dog. These results indicate that compounds stimulating postsynaptic alpha-adrenoceptors may be inactive as agonists of cardiac presynaptic alpha-adrenoceptors within the same animal species. Furthermore, a compound showing selective activity as an antagonist of vascular alpha-adrenoceptors in one species may not necessarily exert the same selective effects in other animals as demonstrated here for prazosin."}
{"id": "PMID:226340", "title": "[Diseases caused by diisocyanates. 1. Irritation of the respiratory system and skin].", "content": "Toluylene diisocyanate (TDI) has an uncommon importance in the production of irritation of respiratory system. In the last few years less volatile isocyanate compounds have been substituted for TDI. Commercial available diphenylmethane diisocyanate (MDI) and polymethylene polyphenyl isocyanate (PAPI) were analyzed in 1971. The analysis indicated the presence of 21% TDI in several samples. It is evident, with respect to the relatively high vapor pressure of TDI, that such impurities will be able to cause air concentrations in excess of the current threshold limit value (TLV) of 0.02 ppm. Liberation of TDI by heat from varnish insulinations is a difficult problem. This problem was described as \"an old hazard in new guise\". Especially, in a soldering process on polyurethane coated wire, excess of TLV is possible in unfavourable conditions. By the regulation that the concentration of TLV must not exceed 0.02 ppm and by the use of new non-volatile isocyanate the risk of acute and subacute intoxications has considerably subsided. Chronic irritations of respiratory system and asthma-like diseases, however represent still an unsolved problem.", "contents": "[Diseases caused by diisocyanates. 1. Irritation of the respiratory system and skin]. Toluylene diisocyanate (TDI) has an uncommon importance in the production of irritation of respiratory system. In the last few years less volatile isocyanate compounds have been substituted for TDI. Commercial available diphenylmethane diisocyanate (MDI) and polymethylene polyphenyl isocyanate (PAPI) were analyzed in 1971. The analysis indicated the presence of 21% TDI in several samples. It is evident, with respect to the relatively high vapor pressure of TDI, that such impurities will be able to cause air concentrations in excess of the current threshold limit value (TLV) of 0.02 ppm. Liberation of TDI by heat from varnish insulinations is a difficult problem. This problem was described as \"an old hazard in new guise\". Especially, in a soldering process on polyurethane coated wire, excess of TLV is possible in unfavourable conditions. By the regulation that the concentration of TLV must not exceed 0.02 ppm and by the use of new non-volatile isocyanate the risk of acute and subacute intoxications has considerably subsided. Chronic irritations of respiratory system and asthma-like diseases, however represent still an unsolved problem."}
{"id": "PMID:226341", "title": "[Diseases caused by diisocyanates. 2. Diisocyanate asthma].", "content": "Diisocyanates are widely used as polymerizing agents in the production of polyurethanes. Exposure to high concentrations of toluene diisocyanate (TDI) causes the development of toxic-irritative symptoms in the respiratory tract. It has been observed that some workers, after repeated exposures and a latent period of months to years, develop asthmatic symptoms upon re-exposure to minute concentrations of diisocyanates. An immunological mechanism for this typical extrinsic asthma has not been adequately documented.", "contents": "[Diseases caused by diisocyanates. 2. Diisocyanate asthma]. Diisocyanates are widely used as polymerizing agents in the production of polyurethanes. Exposure to high concentrations of toluene diisocyanate (TDI) causes the development of toxic-irritative symptoms in the respiratory tract. It has been observed that some workers, after repeated exposures and a latent period of months to years, develop asthmatic symptoms upon re-exposure to minute concentrations of diisocyanates. An immunological mechanism for this typical extrinsic asthma has not been adequately documented."}
{"id": "PMID:226344", "title": "[Effects of morphine on the activity of various dorsal horn neurons of the spinal cord involved in nociception].", "content": "In spinal preparation, morphine exerts a specific direct inhibitory action on the activities of dorsal horn neurones induced by noxious stimuli. The effect of morphine is preferential for the responses evoked by A delta and C fibre afferents and its specificity of action has been demonstrated pharmacologically in terms of isomerism, dose dependency and reversal of the inhibitions by opiate antagonists. These results are in good agreement with recent data related to the localization at the spinal level of opiate receptors, and terminal rich in Enkephalin and substance P. Numerous behavioural and pharmacological investigations suggest that morphine is also acting at the level of the brainstem by reinforcing the activity of descending control systems which modulate the transmission of noxious inputs at the spinal level. However this second modality of action remains extremely difficult to demonstrate from an electrophysiological point of view.", "contents": "[Effects of morphine on the activity of various dorsal horn neurons of the spinal cord involved in nociception]. In spinal preparation, morphine exerts a specific direct inhibitory action on the activities of dorsal horn neurones induced by noxious stimuli. The effect of morphine is preferential for the responses evoked by A delta and C fibre afferents and its specificity of action has been demonstrated pharmacologically in terms of isomerism, dose dependency and reversal of the inhibitions by opiate antagonists. These results are in good agreement with recent data related to the localization at the spinal level of opiate receptors, and terminal rich in Enkephalin and substance P. Numerous behavioural and pharmacological investigations suggest that morphine is also acting at the level of the brainstem by reinforcing the activity of descending control systems which modulate the transmission of noxious inputs at the spinal level. However this second modality of action remains extremely difficult to demonstrate from an electrophysiological point of view."}
{"id": "PMID:226345", "title": "Effects of cholera toxin on thyroid cyclic AMP-dependent protein kinase and ornithine decarboxylase activities.", "content": "Cholera toxin activated beef thyroid cyclic AMP-dependent protein kinase in a dose (0.2 to 8 microgram/ml)-related fashion. Thus, when beef thyroid slices were incubated with toxin (8 microgram/ml) for 90 minutes and then assayed for protein kinase, the activity ratio (i.e. -cyclic AMP/+cyclic AMP) increased from 0.32 +/- 0.02 to 0.77 +/- 0.06. The toxin (5 microgram/ml)-induced increase was abolished by inclusion of ganglioside GM1 in the incubation medium (I50, 0.7 microgram/ml), whereas, gangliosides GD1a and GT1 were without effect. In contrast, TSH-activated protein kinase was unaffected by ganglioside addition. Cholera toxin increased rat thyroid ornithine decarboxylase (ODC) activity in-vitro in a dose (0.1 to 10 microgram/ml)-related fashion [basal, 100 cf cholera toxin (10 microgram/ml), 1500 pmol 14CO2/g tissue/30 min]. The toxin (1 microgram/ml)- (but not TSH-) induced increase in ODC was abolished by inclusion of ganglioside Ga and GT1 were without effect. Cholera toxin stimulation of ODC was inhibited by indomethacin or iodide as are the stimulatory effects of TSH or dibutyryl cyclic AMP. These results demonstrate that although there are differences in the TSH and cholera toxin responses with respect to receptor (ganglioside) interaction, they nevertheless elicit similar intracellular responses in thyroid.", "contents": "Effects of cholera toxin on thyroid cyclic AMP-dependent protein kinase and ornithine decarboxylase activities. Cholera toxin activated beef thyroid cyclic AMP-dependent protein kinase in a dose (0.2 to 8 microgram/ml)-related fashion. Thus, when beef thyroid slices were incubated with toxin (8 microgram/ml) for 90 minutes and then assayed for protein kinase, the activity ratio (i.e. -cyclic AMP/+cyclic AMP) increased from 0.32 +/- 0.02 to 0.77 +/- 0.06. The toxin (5 microgram/ml)-induced increase was abolished by inclusion of ganglioside GM1 in the incubation medium (I50, 0.7 microgram/ml), whereas, gangliosides GD1a and GT1 were without effect. In contrast, TSH-activated protein kinase was unaffected by ganglioside addition. Cholera toxin increased rat thyroid ornithine decarboxylase (ODC) activity in-vitro in a dose (0.1 to 10 microgram/ml)-related fashion [basal, 100 cf cholera toxin (10 microgram/ml), 1500 pmol 14CO2/g tissue/30 min]. The toxin (1 microgram/ml)- (but not TSH-) induced increase in ODC was abolished by inclusion of ganglioside Ga and GT1 were without effect. Cholera toxin stimulation of ODC was inhibited by indomethacin or iodide as are the stimulatory effects of TSH or dibutyryl cyclic AMP. These results demonstrate that although there are differences in the TSH and cholera toxin responses with respect to receptor (ganglioside) interaction, they nevertheless elicit similar intracellular responses in thyroid."}
{"id": "PMID:226346", "title": "Subcellular localization of dopamine in the anterior pituitary gland of the rat: apparent association of dopamine with prolactin secretory granules.", "content": "The subcellular compartmentalization of endogenous dopamine in the anterior pituitary gland of the rat was investigated using continuous sucrose density gradient centrifugation. When anterior pituitary homogenates were layered on continuous sucrose density gradients (1.0--2.0 M) and centrifuged for 60 min at 40,000 X g, dopamine recovered from the gradients was associated with two sets of subcellular particles. The particles in one set were recovered near the top of the gradient, whereas those in the other set were recovered near the bottom of the gradient in the region where particles containing PRL were also found. In fact, these dense dopamine-containing particles could not be separated from those particles which contained PRL. These findings were suggestive that dopamine and PRL were present in the same particle, viz. the PRL secretory granule. This interpretation was further strengthened when it was established that the PRL-containing granules were separable on the gradient from granules which contained GH, LH, FSH, ACTH, and TSH. When [3H]dopamine was added to the solution in which the anterior lobes were homogenized, no radio-activity was found to be associated with the dense dopamine-containing particles. Also, the addition of a large excess of nonradiolabeled dopamine at the time of homogenization did not influence the amount of dopamine associated with the dense particles. Thus, the apparent association of dopamine with PRL secretory granules was not an artifact of the homogenization process per se. Therefore, it is concluded that an association exists between intracellular dopamine and the PRL secretory granule.", "contents": "Subcellular localization of dopamine in the anterior pituitary gland of the rat: apparent association of dopamine with prolactin secretory granules. The subcellular compartmentalization of endogenous dopamine in the anterior pituitary gland of the rat was investigated using continuous sucrose density gradient centrifugation. When anterior pituitary homogenates were layered on continuous sucrose density gradients (1.0--2.0 M) and centrifuged for 60 min at 40,000 X g, dopamine recovered from the gradients was associated with two sets of subcellular particles. The particles in one set were recovered near the top of the gradient, whereas those in the other set were recovered near the bottom of the gradient in the region where particles containing PRL were also found. In fact, these dense dopamine-containing particles could not be separated from those particles which contained PRL. These findings were suggestive that dopamine and PRL were present in the same particle, viz. the PRL secretory granule. This interpretation was further strengthened when it was established that the PRL-containing granules were separable on the gradient from granules which contained GH, LH, FSH, ACTH, and TSH. When [3H]dopamine was added to the solution in which the anterior lobes were homogenized, no radio-activity was found to be associated with the dense dopamine-containing particles. Also, the addition of a large excess of nonradiolabeled dopamine at the time of homogenization did not influence the amount of dopamine associated with the dense particles. Thus, the apparent association of dopamine with PRL secretory granules was not an artifact of the homogenization process per se. Therefore, it is concluded that an association exists between intracellular dopamine and the PRL secretory granule."}
{"id": "PMID:226347", "title": "Plasma free tryptophan, brain serotonin, and an endocrine profile of the genetically obese hyperglycemic mouse at 4--5 months of age.", "content": "Genetically obese hyperglycemic mice (ob/ob) were compared with their nonlittermate lean controls at 4-5 months of age with regard to brain serotonin, pituitary ACTH content, and circulating levels of glucose, glucagon, insulin, TSH, T3, T4, total tryptophan and free tryptophan. Brain serotonin pituitary ACTH content, and plasma insulin, glucose, total tryptophan, and free tryptophan were all significantly higher in obese mice than in the controls. TSH, T3, and T4 were not significantly different in obese mice vs. controls, suggesting that the obese mouse is euthyroid. Fasting improved but failed to normalize the glucose and insulin levels or insulin to glucagon ratios. Since serotonin is an important neurotransmitter with regard to hypothalamic-pituitary function and since its levels in the brain are dependent on the availability of tryptophan, the findings of elevated levels of free tryptophan in the plasma and serotonin in the brain of the obese hyperglycemic mouse may help to explain some of the previously observed abnormalities of pituitary hormone secretion in these animals.", "contents": "Plasma free tryptophan, brain serotonin, and an endocrine profile of the genetically obese hyperglycemic mouse at 4--5 months of age. Genetically obese hyperglycemic mice (ob/ob) were compared with their nonlittermate lean controls at 4-5 months of age with regard to brain serotonin, pituitary ACTH content, and circulating levels of glucose, glucagon, insulin, TSH, T3, T4, total tryptophan and free tryptophan. Brain serotonin pituitary ACTH content, and plasma insulin, glucose, total tryptophan, and free tryptophan were all significantly higher in obese mice than in the controls. TSH, T3, and T4 were not significantly different in obese mice vs. controls, suggesting that the obese mouse is euthyroid. Fasting improved but failed to normalize the glucose and insulin levels or insulin to glucagon ratios. Since serotonin is an important neurotransmitter with regard to hypothalamic-pituitary function and since its levels in the brain are dependent on the availability of tryptophan, the findings of elevated levels of free tryptophan in the plasma and serotonin in the brain of the obese hyperglycemic mouse may help to explain some of the previously observed abnormalities of pituitary hormone secretion in these animals."}
{"id": "PMID:226348", "title": "Sulfhydryl reagent-induced insulin release and 45Ca++ fluxes in Syrian hamster insulinoma cells.", "content": "Dispersed single cell suspensions of Syrian hamster insulinoma cells were used to study the effects of a variety of sulfhydryl-binding reagents on insulin release and 45Ca++ flux. Incubation of cells with several organic mercurials resulted in a rapid increase in 45Ca++ uptake as well as increased efflux in cells which had been prelabeled with 45Ca++. Concomitant with increased calcium uptake was a 4- to 5-fold increase in insulin released into the medium. Incubation with alkylating reagents such as iodoacetamide and N-ethyl maleimide or dithiol reagents such as 5,5'-dithiobis (2-nitrobenzoic acid) failed to stimulate either 45Ca++ flux or insulin release. Elimination of medium calscium or preincubation of cells with N-ethyl maleimide resulted in approximately 50% inhibition of mercurial-induced insulin release from these cells. 8-(N,N2-diethylamino)Octyl-3,4,5-trimethoxybenzoate or alpha-isopropyl-alpha [(N-methyl-N-homoveratryl)-gamma-aminopropyl]3,4,5'-trimethoxyphenylacetonitrite hydrochloride, agents which block potassium (40 mM)-stimulated calcium flux and insulin release, failed to inhibit mercurial-induced calcium flux or insulin secretion. These results indicate that sulfhydryl-binding reagents, through their interaction with critical thiol groups, promote insulin release in these insulinoma cells by inducing changes in calcium fluxes. It is possible that these thiol groups regulate calcium metabolism and, thus, insulin release under physiological conditions.", "contents": "Sulfhydryl reagent-induced insulin release and 45Ca++ fluxes in Syrian hamster insulinoma cells. Dispersed single cell suspensions of Syrian hamster insulinoma cells were used to study the effects of a variety of sulfhydryl-binding reagents on insulin release and 45Ca++ flux. Incubation of cells with several organic mercurials resulted in a rapid increase in 45Ca++ uptake as well as increased efflux in cells which had been prelabeled with 45Ca++. Concomitant with increased calcium uptake was a 4- to 5-fold increase in insulin released into the medium. Incubation with alkylating reagents such as iodoacetamide and N-ethyl maleimide or dithiol reagents such as 5,5'-dithiobis (2-nitrobenzoic acid) failed to stimulate either 45Ca++ flux or insulin release. Elimination of medium calscium or preincubation of cells with N-ethyl maleimide resulted in approximately 50% inhibition of mercurial-induced insulin release from these cells. 8-(N,N2-diethylamino)Octyl-3,4,5-trimethoxybenzoate or alpha-isopropyl-alpha [(N-methyl-N-homoveratryl)-gamma-aminopropyl]3,4,5'-trimethoxyphenylacetonitrite hydrochloride, agents which block potassium (40 mM)-stimulated calcium flux and insulin release, failed to inhibit mercurial-induced calcium flux or insulin secretion. These results indicate that sulfhydryl-binding reagents, through their interaction with critical thiol groups, promote insulin release in these insulinoma cells by inducing changes in calcium fluxes. It is possible that these thiol groups regulate calcium metabolism and, thus, insulin release under physiological conditions."}
{"id": "PMID:226349", "title": "The role of sulfhydryl groups in thyrotropin binding and adenylate cyclase activities of thyroid plasma membranes.", "content": "The effects of sulfhydryl (SH) reagents on the binding of TSH to thyroid membranes and on membrane adenylate cyclase activity were studied. Diamide, a SH-oxidizing agent, enhanced [125I]iodo-TSH binding to thyroid membranes in a dose-dependent manner. On the contrary, dithiothreitol (DTT), a disulfide-reducing reagent, markedly inhibited this activity in a dose-dependent manner. These effects could not be attributed to a direct interaction between the reagents and the radioactive TSH. Scatchard plot analysis of the data was limited by curvilinear plots but suggested that diamide increases while DTT decreases the affinity of the receptors for TSH in thyroid membranes, neither reagent appeared to influence the capacity of TSH binding by membranes. The effects of diamide and DTT on adenylate cyclase activity of thyroid plasma membranes were just the opposite of their effects on TSH binding. Thus, diamide inhibited adenylate cyclase activity of thyroid plasma membranes while DTT increased basal enzyme activity and slightly but not significantly increased TSH-stimulated enzyme activity. The data suggest a possible physiological role for SH and disulfide groups of thyroid membranes in modulation of thyroidal activity.", "contents": "The role of sulfhydryl groups in thyrotropin binding and adenylate cyclase activities of thyroid plasma membranes. The effects of sulfhydryl (SH) reagents on the binding of TSH to thyroid membranes and on membrane adenylate cyclase activity were studied. Diamide, a SH-oxidizing agent, enhanced [125I]iodo-TSH binding to thyroid membranes in a dose-dependent manner. On the contrary, dithiothreitol (DTT), a disulfide-reducing reagent, markedly inhibited this activity in a dose-dependent manner. These effects could not be attributed to a direct interaction between the reagents and the radioactive TSH. Scatchard plot analysis of the data was limited by curvilinear plots but suggested that diamide increases while DTT decreases the affinity of the receptors for TSH in thyroid membranes, neither reagent appeared to influence the capacity of TSH binding by membranes. The effects of diamide and DTT on adenylate cyclase activity of thyroid plasma membranes were just the opposite of their effects on TSH binding. Thus, diamide inhibited adenylate cyclase activity of thyroid plasma membranes while DTT increased basal enzyme activity and slightly but not significantly increased TSH-stimulated enzyme activity. The data suggest a possible physiological role for SH and disulfide groups of thyroid membranes in modulation of thyroidal activity."}
{"id": "PMID:226350", "title": "Steroidogenesis in isolated cells and mitochondria of rat Snell adrenocortical carcinoma 494.", "content": "ACTH produced a 75% increase in pregnenolone biosynthesis from endogenous precursors in isolated cells prepared from the rat Snell adrenocortical carcinoma 494. On the addition of 24- and 25-hydroxycholesterol to the tumor cells, the rate of pregnenolone synthesis increased 10-fold but was insensitive to the presence of ACTH. Addition of lipoprotein cholesterol resulted in increased pregnenolone biosynthesis when ACTH was present. High density lipoprotein cholesterol appeared to be internalized and used for steroidogenesis preferentially to low density lipoprotein cholesterol. The cholesterol ester hydrolase activity of the cytosolic fraction of the tumor was found to be extremely low compared to that of the normal adrenal cell. These results, noting also the low cholesterol content of the tumor cells, suggested that the lack of availability of cholesterol was the factor responsible for the poor steroidogenic response of the cells to ACTH. The major steroid product of the tumor cells was determined to be deoxycorticosterone. This correlated with the low levels of steroid 11-beta-hydroxylase activity detected in the adrenal tumor mitochondria compared to the mitochondrial cholesterol desmolase activity. Little of the mitochondrial cytochrome P-450 appeared to function in a steroid 11-beta-hydroxylase complex.", "contents": "Steroidogenesis in isolated cells and mitochondria of rat Snell adrenocortical carcinoma 494. ACTH produced a 75% increase in pregnenolone biosynthesis from endogenous precursors in isolated cells prepared from the rat Snell adrenocortical carcinoma 494. On the addition of 24- and 25-hydroxycholesterol to the tumor cells, the rate of pregnenolone synthesis increased 10-fold but was insensitive to the presence of ACTH. Addition of lipoprotein cholesterol resulted in increased pregnenolone biosynthesis when ACTH was present. High density lipoprotein cholesterol appeared to be internalized and used for steroidogenesis preferentially to low density lipoprotein cholesterol. The cholesterol ester hydrolase activity of the cytosolic fraction of the tumor was found to be extremely low compared to that of the normal adrenal cell. These results, noting also the low cholesterol content of the tumor cells, suggested that the lack of availability of cholesterol was the factor responsible for the poor steroidogenic response of the cells to ACTH. The major steroid product of the tumor cells was determined to be deoxycorticosterone. This correlated with the low levels of steroid 11-beta-hydroxylase activity detected in the adrenal tumor mitochondria compared to the mitochondrial cholesterol desmolase activity. Little of the mitochondrial cytochrome P-450 appeared to function in a steroid 11-beta-hydroxylase complex."}
{"id": "PMID:226351", "title": "Effects of insulin on glucose metabolism and glucose transport in fat cells of hormone-treated hypophysectomized rats: evidence that growth hormone restricts glucose transport.", "content": "In earlier studies we have shown that insulin does not stimulate glucose incorporation in adipocytes of hypophysectomized (hypox) rats. Basal glucose incorporation is decreased, although basal 3-O-methylglycose transport is very rapid and cannot be further stimulated by insulin. In this study we treated hypox rats with human GH, ACTH, and T3, alone or in combination, and examined the effects of insulin on glucose incorporation into fat cells and on 3-O-methylglucose transport. The results show that chronic administration of T3 alone to hypox rats partially restores glucose incorporation into fat cells and, in combination with ACTH, completely restores this incorporation. The two hormones have no effect on the glucose carrier system. The transport rate under T3 and ACTH replacement therapy continues to proceed at a maximal rate, so that basal glucose incorporation is high but not further enhanced by insulin. In contrast, administration of human GH to hypox rats does not influence glucose incorporation but has a marked effect on glucose transport. The basal glucose transport rate returns toward normal and again responds to insulin. This suggests 1) that enzyme activities responsible for the lipogenetic capacity of the fat cell are decreased in hypox rats and returned toward normal by the combined T3/ACTH treatment, and 2) that the limitation of glucose transport in the fat cell is controlled by GH. GH seems to induce a change of the glucose-carrier system; it leads to a restriction of glucose transport, which is acutely modulated by insulin.", "contents": "Effects of insulin on glucose metabolism and glucose transport in fat cells of hormone-treated hypophysectomized rats: evidence that growth hormone restricts glucose transport. In earlier studies we have shown that insulin does not stimulate glucose incorporation in adipocytes of hypophysectomized (hypox) rats. Basal glucose incorporation is decreased, although basal 3-O-methylglycose transport is very rapid and cannot be further stimulated by insulin. In this study we treated hypox rats with human GH, ACTH, and T3, alone or in combination, and examined the effects of insulin on glucose incorporation into fat cells and on 3-O-methylglucose transport. The results show that chronic administration of T3 alone to hypox rats partially restores glucose incorporation into fat cells and, in combination with ACTH, completely restores this incorporation. The two hormones have no effect on the glucose carrier system. The transport rate under T3 and ACTH replacement therapy continues to proceed at a maximal rate, so that basal glucose incorporation is high but not further enhanced by insulin. In contrast, administration of human GH to hypox rats does not influence glucose incorporation but has a marked effect on glucose transport. The basal glucose transport rate returns toward normal and again responds to insulin. This suggests 1) that enzyme activities responsible for the lipogenetic capacity of the fat cell are decreased in hypox rats and returned toward normal by the combined T3/ACTH treatment, and 2) that the limitation of glucose transport in the fat cell is controlled by GH. GH seems to induce a change of the glucose-carrier system; it leads to a restriction of glucose transport, which is acutely modulated by insulin."}
{"id": "PMID:226352", "title": "Evaluation of histological classification in early gastric cancer (an analysis of 300 cases).", "content": "Using the Lauren approach of histological classification, 300 cases of early gastric cancer (EGC) were analysed with regard to their age distribution, to predisposing lesions, including gastritis, and survival rate. The average age of onset for EGC of the diffuse type is 56, ten years earlier than for the intestinal type. There was a significantly high percentage of EGC of the diffuse type without gastritis. On the other hand, gastritis in pernicious anaemia falls in the high-risk group. The survival rate in our cases is 98%, corrected for age. The results show that it is of utmost importance to differentiate between the histological types of gastric carcinoma; for there may be indeed a difference in pathogenesis and aetiology.", "contents": "Evaluation of histological classification in early gastric cancer (an analysis of 300 cases). Using the Lauren approach of histological classification, 300 cases of early gastric cancer (EGC) were analysed with regard to their age distribution, to predisposing lesions, including gastritis, and survival rate. The average age of onset for EGC of the diffuse type is 56, ten years earlier than for the intestinal type. There was a significantly high percentage of EGC of the diffuse type without gastritis. On the other hand, gastritis in pernicious anaemia falls in the high-risk group. The survival rate in our cases is 98%, corrected for age. The results show that it is of utmost importance to differentiate between the histological types of gastric carcinoma; for there may be indeed a difference in pathogenesis and aetiology."}
{"id": "PMID:226353", "title": "Investigations on the lung and kidney function in workers exposed to cadmium.", "content": "The kidney seems more sensitive to the chronic effect of cadmium than the lung. Only minor impairments of lung function (mild form of obstructive lung disease) were found after long-term occupational exposure (less than 20 yr) to moderate concentration of cadmium oxide dust and fume. This conclusion, cannot, however be extrapolated to acute or subacute inhalational exposure. The nephrotoxicity of cadmium consists in a tubular dysfunction characterized by an increased excretion of beta 2-microglobulin and giving rise to the classical tubular proteinuria and in a glomerular dysfunction evidenced by an increased excretion of high molecular weight proteins and increased levels of beta 2-microglobulin and creatinine in plasma and giving rise to a glomerular type proteinuria. These renal changes were mainly found in workers whose cadmium concentration at time of the survey exceeded 1 microgram Cd/100 ml in blood and 10 microgram Cd/g creatinine in urine. It should, however, be stressed that higher levels of Cd in blood and in urine are not necessarily associated with the presence of excessive proteinuria. In newly exposed workers, the Cd level in blood increases progressively to a plateau after several weeks. Cadmium level in urine fluctuates more. In workers exposed for several months to an airborne concentration exceeding 200 microgram/m3, Cd concentration in urine seems mainly influenced by recent exposure.", "contents": "Investigations on the lung and kidney function in workers exposed to cadmium. The kidney seems more sensitive to the chronic effect of cadmium than the lung. Only minor impairments of lung function (mild form of obstructive lung disease) were found after long-term occupational exposure (less than 20 yr) to moderate concentration of cadmium oxide dust and fume. This conclusion, cannot, however be extrapolated to acute or subacute inhalational exposure. The nephrotoxicity of cadmium consists in a tubular dysfunction characterized by an increased excretion of beta 2-microglobulin and giving rise to the classical tubular proteinuria and in a glomerular dysfunction evidenced by an increased excretion of high molecular weight proteins and increased levels of beta 2-microglobulin and creatinine in plasma and giving rise to a glomerular type proteinuria. These renal changes were mainly found in workers whose cadmium concentration at time of the survey exceeded 1 microgram Cd/100 ml in blood and 10 microgram Cd/g creatinine in urine. It should, however, be stressed that higher levels of Cd in blood and in urine are not necessarily associated with the presence of excessive proteinuria. In newly exposed workers, the Cd level in blood increases progressively to a plateau after several weeks. Cadmium level in urine fluctuates more. In workers exposed for several months to an airborne concentration exceeding 200 microgram/m3, Cd concentration in urine seems mainly influenced by recent exposure."}
{"id": "PMID:226354", "title": "A study of the relationship between cadmium concentrations in urine and renal effects of cadmium.", "content": "The relationship between urinary cadmium concentration expressed as microgram/g creatinine and renal effects of cadmium exposure was studied in 542 inhabitants over 20 years of age who lived in the Jinzu River basin which is polluted by cadmium. Cadmium concentration in urine was employed as the index of cadmium exposure. Total protein with glucose, beta 2-microglobulin, retinol binding protein, and proline served as indices of renal effects. The prevalent rate of high beta 2-microglobulin excretion was the highest among these indices both in men and women. Prevalence rates of indices of renal effects increased proportionally with increasing cadmium concentrations in urine and probit linear regression lines could be calculated between them. The urinary cadmium concentrations corresponding to 1% prevalence rates of indices of the renal effects were calculated by the regression line. For beta 2-microglobulin, 3.2 microgram Cd/g creatinine and 5.2 microgram Cd/g creatinine were obtained in men and women, respectively. This method may be useful for evaluating the risk of renal damage of exposed inhabitants.", "contents": "A study of the relationship between cadmium concentrations in urine and renal effects of cadmium. The relationship between urinary cadmium concentration expressed as microgram/g creatinine and renal effects of cadmium exposure was studied in 542 inhabitants over 20 years of age who lived in the Jinzu River basin which is polluted by cadmium. Cadmium concentration in urine was employed as the index of cadmium exposure. Total protein with glucose, beta 2-microglobulin, retinol binding protein, and proline served as indices of renal effects. The prevalent rate of high beta 2-microglobulin excretion was the highest among these indices both in men and women. Prevalence rates of indices of renal effects increased proportionally with increasing cadmium concentrations in urine and probit linear regression lines could be calculated between them. The urinary cadmium concentrations corresponding to 1% prevalence rates of indices of the renal effects were calculated by the regression line. For beta 2-microglobulin, 3.2 microgram Cd/g creatinine and 5.2 microgram Cd/g creatinine were obtained in men and women, respectively. This method may be useful for evaluating the risk of renal damage of exposed inhabitants."}
{"id": "PMID:226355", "title": "Exposure and accumulation of cadmium in populations from Japan, the United States, and Sweden.", "content": "Studies were carried out in Japan, United States, and Sweden regarding comparability of analytical methods for cadmium, daily intake of cadmium via food, daily amount of cadmium in feces, concentrations of cadmium in different tissues and the body burden of cadmium, urinary excretion of cadmium and cadmium concentrations in blood. It was found that the cadmium intake via food among adults is about 35 mug/day in Japan (Tokyo) and about 17 mug/day in the U.S. (Dallas) and Sweden (Stockholm). It varies with age in a way similar to calorie intake. Body burden increases rapidly with age. The half-time of cadmium is longer in muscles than in liver or kidneys. In the cross-sectional population samples studied (smokers and nonsmokers mixed) the average cadmium body burden at age 45 was about 21 mg in Japan, 9 mg in the U.S., and 6 mg in Sweden. Among nonsmokers in the U.S. and Sweden the body burden at age 45 was about 5-6 mg. The difference in average body burden for smokers and nonsmokers is explained by differences in smoking habits. Cadmium excretion in urine was closely correlated with body burden and about 0.005-0.01% of body burden is excreted daily in urine. Cadmium concentration in the blood was a good indicator of average recent intake over a 3-month period. Neither blood cadmium nor urine cadmium changed immediately after an increase of exposure level.", "contents": "Exposure and accumulation of cadmium in populations from Japan, the United States, and Sweden. Studies were carried out in Japan, United States, and Sweden regarding comparability of analytical methods for cadmium, daily intake of cadmium via food, daily amount of cadmium in feces, concentrations of cadmium in different tissues and the body burden of cadmium, urinary excretion of cadmium and cadmium concentrations in blood. It was found that the cadmium intake via food among adults is about 35 mug/day in Japan (Tokyo) and about 17 mug/day in the U.S. (Dallas) and Sweden (Stockholm). It varies with age in a way similar to calorie intake. Body burden increases rapidly with age. The half-time of cadmium is longer in muscles than in liver or kidneys. In the cross-sectional population samples studied (smokers and nonsmokers mixed) the average cadmium body burden at age 45 was about 21 mg in Japan, 9 mg in the U.S., and 6 mg in Sweden. Among nonsmokers in the U.S. and Sweden the body burden at age 45 was about 5-6 mg. The difference in average body burden for smokers and nonsmokers is explained by differences in smoking habits. Cadmium excretion in urine was closely correlated with body burden and about 0.005-0.01% of body burden is excreted daily in urine. Cadmium concentration in the blood was a good indicator of average recent intake over a 3-month period. Neither blood cadmium nor urine cadmium changed immediately after an increase of exposure level."}
{"id": "PMID:226356", "title": "Recent results of health examinations on the general population in cadmium-polluted and control areas in Japan.", "content": "Health examinations by a revised method aimed at detecting renal tubular dysfunctions more effectively were conducted on the general population aged 50 years and over in cadmium-polluted areas (1826 persons) and control areas (1611 persons) in four prefectures in Japan in 1976. Although detailed analysis of the data is not yet completed, some of the results obtained are described here. The prevalence of glucosuria and low molecular weight proteinuria, frequency of decreased % TRP, and cadmium concentrations in urine are higher in the cadmium-polluted areas than in the controls. Clinically diagnosed cases with tubular dysfunctions seem to follow the same trend as above, though  these cases are very few in number and they are limited to the advanced age group. When cadmium concentration in rice is taken as an index, a dose-response relationship is not necessarity explicit in the observations by prefecture. However, suggestive data are obtained in the observation by district in one cadmium-polluted area.", "contents": "Recent results of health examinations on the general population in cadmium-polluted and control areas in Japan. Health examinations by a revised method aimed at detecting renal tubular dysfunctions more effectively were conducted on the general population aged 50 years and over in cadmium-polluted areas (1826 persons) and control areas (1611 persons) in four prefectures in Japan in 1976. Although detailed analysis of the data is not yet completed, some of the results obtained are described here. The prevalence of glucosuria and low molecular weight proteinuria, frequency of decreased % TRP, and cadmium concentrations in urine are higher in the cadmium-polluted areas than in the controls. Clinically diagnosed cases with tubular dysfunctions seem to follow the same trend as above, though  these cases are very few in number and they are limited to the advanced age group. When cadmium concentration in rice is taken as an index, a dose-response relationship is not necessarity explicit in the observations by prefecture. However, suggestive data are obtained in the observation by district in one cadmium-polluted area."}
{"id": "PMID:226357", "title": "Adrenal-testis interaction in the stallion.", "content": "The authors describe the short and long term effects of synthetic adrenocorticotrophin and of cortisol on peripheral plasma testosterone concentrations in 2 stallions. A single injection of either hormone temporarily raised plasma testosterone concentrations but repeated injection (twice daily for 5 days) depressed plasma testosterone concentrations. Cessation of treatment was followed by a rise in plasma testosterone to concentrations higher than those in the pretreatment period. These findings are briefly discussed.", "contents": "Adrenal-testis interaction in the stallion. The authors describe the short and long term effects of synthetic adrenocorticotrophin and of cortisol on peripheral plasma testosterone concentrations in 2 stallions. A single injection of either hormone temporarily raised plasma testosterone concentrations but repeated injection (twice daily for 5 days) depressed plasma testosterone concentrations. Cessation of treatment was followed by a rise in plasma testosterone to concentrations higher than those in the pretreatment period. These findings are briefly discussed."}
{"id": "PMID:226359", "title": "The ATP synthetase of Escherichia coli K12: purification of the enzyme and reconstitution of energy-transducing activities.", "content": "The ATP synthetase of Escherichia coli K12 was purified by a simple procedure. The dicyclohexylcarbodiimide-sensitive ATPase activity was enriched 21-fold. The ATP synthetase preparation contained the eight polypeptides (alpha, beta, gamma, a,delta, b,espilon, c) of the enzyme and a residual contamination (4% of the total protein) as shown by dodecylsulfate/polyacrylamide electrophoresis. The polypeptide c was specifically labelled with [14C]dicyclohexylcarbodiimide. Energy-transducing activities were reconstituted from soybean phospholipids and the purified enzyme. The proteoliposomes exhibited a significantly higher ATP-32Pi exchange activity and a higher proton-translocating activity as compared to the untreated membranes.", "contents": "The ATP synthetase of Escherichia coli K12: purification of the enzyme and reconstitution of energy-transducing activities. The ATP synthetase of Escherichia coli K12 was purified by a simple procedure. The dicyclohexylcarbodiimide-sensitive ATPase activity was enriched 21-fold. The ATP synthetase preparation contained the eight polypeptides (alpha, beta, gamma, a,delta, b,espilon, c) of the enzyme and a residual contamination (4% of the total protein) as shown by dodecylsulfate/polyacrylamide electrophoresis. The polypeptide c was specifically labelled with [14C]dicyclohexylcarbodiimide. Energy-transducing activities were reconstituted from soybean phospholipids and the purified enzyme. The proteoliposomes exhibited a significantly higher ATP-32Pi exchange activity and a higher proton-translocating activity as compared to the untreated membranes."}
{"id": "PMID:226361", "title": "Nucleotide sequence of the Hind-C fragment of simian virus 40 DNA. Comparison of the 5'-untranslated region of wild-type virus and of some deletion Mutants.", "content": "We report here the nucleotide sequence of the wild-type simian virus 40 (strain 776) restriction fragment Hind-C-P1 DNA and of the homologous region of various mutant DNAs which lack part of this fragment. During this work, we detected between EcoRII fragments N and G an additional, 17-base-pair EcoRII fragment, fragment P, which had previously been overlooked. Also, an additional dTpdG dinucleotide at residues L 339--340 was observed by sequence analysis of the DNA minus (E) strand; the presence of this dinucleotide was masked on sequencing patterns of the plus strand due to the persistence (during gel electrophoresis) of some secondary structures in the strand's 5'-terminal region. These nucleotide additions raise the total length of SV40 DNA to 5243 base pairs. The longest tandemly repeated segment in SV40 DNA now extends over 72 base pairs. SV40 deletion mutants dl 893 and dl 894 and SV40 strains Rh 911 and 1801 all lack an identical 72-base-pair-long DNA segment in the Hind-C region. This deletion corresponds precisely to one of the two aforementioned large tandemly repeated sequences. Mutant dl 895 lacks 66 base pairs, 63 of which are part of the former repetition. All these mutants, except dl 895, very probably were generated by an intramolecular, homologous recombination event. The 40-base-pair deletion in mutant dl 1811 includes the major capping site of SV40 late RNA. dl 1812 lacks only three base pairs, which are part of the overlapping HhaI and HpaII restriction sites at position 0.725--0.726.", "contents": "Nucleotide sequence of the Hind-C fragment of simian virus 40 DNA. Comparison of the 5'-untranslated region of wild-type virus and of some deletion Mutants. We report here the nucleotide sequence of the wild-type simian virus 40 (strain 776) restriction fragment Hind-C-P1 DNA and of the homologous region of various mutant DNAs which lack part of this fragment. During this work, we detected between EcoRII fragments N and G an additional, 17-base-pair EcoRII fragment, fragment P, which had previously been overlooked. Also, an additional dTpdG dinucleotide at residues L 339--340 was observed by sequence analysis of the DNA minus (E) strand; the presence of this dinucleotide was masked on sequencing patterns of the plus strand due to the persistence (during gel electrophoresis) of some secondary structures in the strand's 5'-terminal region. These nucleotide additions raise the total length of SV40 DNA to 5243 base pairs. The longest tandemly repeated segment in SV40 DNA now extends over 72 base pairs. SV40 deletion mutants dl 893 and dl 894 and SV40 strains Rh 911 and 1801 all lack an identical 72-base-pair-long DNA segment in the Hind-C region. This deletion corresponds precisely to one of the two aforementioned large tandemly repeated sequences. Mutant dl 895 lacks 66 base pairs, 63 of which are part of the former repetition. All these mutants, except dl 895, very probably were generated by an intramolecular, homologous recombination event. The 40-base-pair deletion in mutant dl 1811 includes the major capping site of SV40 late RNA. dl 1812 lacks only three base pairs, which are part of the overlapping HhaI and HpaII restriction sites at position 0.725--0.726."}
{"id": "PMID:226362", "title": "Transcription by eukaryotic RNA polymerases A and B of chromatin assembled in vitro.", "content": "Chromatin was assembled in vitro from simian virus 40 DNA form I and the calf-thymus four histones H2A, H2B, H3 and H4. Transcription with calf thymus RNA polymerases A and B (I and II) was greatly inhibited. Nucleosomes were found to inhibit both RNA chain initiation and elongation. The inhibition of elongation could be relieved by increasing ionic strength, suggesting that electrostatic interactions between histone octamer and DNA have to be broken for RNA polymerase to transcribe DNA organised into nucleosomes.", "contents": "Transcription by eukaryotic RNA polymerases A and B of chromatin assembled in vitro. Chromatin was assembled in vitro from simian virus 40 DNA form I and the calf-thymus four histones H2A, H2B, H3 and H4. Transcription with calf thymus RNA polymerases A and B (I and II) was greatly inhibited. Nucleosomes were found to inhibit both RNA chain initiation and elongation. The inhibition of elongation could be relieved by increasing ionic strength, suggesting that electrostatic interactions between histone octamer and DNA have to be broken for RNA polymerase to transcribe DNA organised into nucleosomes."}
{"id": "PMID:226363", "title": "Affinity chromatography of the beta-adrenergic receptor from turkey erythrocytes.", "content": "The beta 1-adrenergic receptors of turkey erythrocyte membranes have been identified by binding of the radioactively labeled antagonist (--)-[3H]dihydroalprenolol, solubilized by treatment of the membranes with the detergent digitonin, and purified by affinity chromatography. Binding of (--)-[3H]dihydroalprenolol to the membranes occurred to a single class of non-cooperative binding sites (0.2--0.3 pmol/mg protein) with a equilibrium dissociation constant (Kd) of 8 (+/- 2) nM. These sites were identified as the functional, adenylate-cyclase-linked beta 1-adrenergic receptors on the basis of: firstly, the fast association and dissociation binding kinetics at 30 degrees C; secondly, the stereospecific displacement of bound (--)-[3H]dihydroalprenolol by beta-adrenergic agonists and antagonists; and thirdly, the order of potencies for agonists to displace bound tracer (isoproterenol congruent to protokylol greater than norepinephrine congruent to epinephrine) similar to the one found for adenylate cyclase activation, and typical for beta 1-adrenergic receptors. Treatment of the membranes with the detergent digitonin solubilized 30% of the receptors in an active form. Digitonin solubilized also adenylate cyclase activity with a yield of 20 to 30%, provided the membranes were first treated with an effector known to produce a persistent active state of the enzyme: e.g. sodium fluoride. Binding sites for guanine nucleotides ([3H]p[NH]ppG) were solubilized as well. Their concentration (24 pmol/mg protein) was in large excess over the concentration of solubilized receptors (0.30--0.45 pmol/mg protein). Solubilized receptors were purified 500--2000-fold by affinity chromatography with a 25 to 35% yield, using an alprenolol-agarose affinity matrix. Affinity purified receptors were devoid of measurable adenylate cyclase activity and guanine nucleotide binding sites, thus showing that receptors and adenylate cyclase are distinct membrane constituents, and that guanine nucleotides apparently do not bind directly to the receptor molecules. Membrane-bound, solubilized and purified receptors were sensitive to inactivation by dithiothreitol, but not by N-ethylmaleimide, suggesting that receptors are at least partly constituted of protein molecules, with essential disulfide bonds.", "contents": "Affinity chromatography of the beta-adrenergic receptor from turkey erythrocytes. The beta 1-adrenergic receptors of turkey erythrocyte membranes have been identified by binding of the radioactively labeled antagonist (--)-[3H]dihydroalprenolol, solubilized by treatment of the membranes with the detergent digitonin, and purified by affinity chromatography. Binding of (--)-[3H]dihydroalprenolol to the membranes occurred to a single class of non-cooperative binding sites (0.2--0.3 pmol/mg protein) with a equilibrium dissociation constant (Kd) of 8 (+/- 2) nM. These sites were identified as the functional, adenylate-cyclase-linked beta 1-adrenergic receptors on the basis of: firstly, the fast association and dissociation binding kinetics at 30 degrees C; secondly, the stereospecific displacement of bound (--)-[3H]dihydroalprenolol by beta-adrenergic agonists and antagonists; and thirdly, the order of potencies for agonists to displace bound tracer (isoproterenol congruent to protokylol greater than norepinephrine congruent to epinephrine) similar to the one found for adenylate cyclase activation, and typical for beta 1-adrenergic receptors. Treatment of the membranes with the detergent digitonin solubilized 30% of the receptors in an active form. Digitonin solubilized also adenylate cyclase activity with a yield of 20 to 30%, provided the membranes were first treated with an effector known to produce a persistent active state of the enzyme: e.g. sodium fluoride. Binding sites for guanine nucleotides ([3H]p[NH]ppG) were solubilized as well. Their concentration (24 pmol/mg protein) was in large excess over the concentration of solubilized receptors (0.30--0.45 pmol/mg protein). Solubilized receptors were purified 500--2000-fold by affinity chromatography with a 25 to 35% yield, using an alprenolol-agarose affinity matrix. Affinity purified receptors were devoid of measurable adenylate cyclase activity and guanine nucleotide binding sites, thus showing that receptors and adenylate cyclase are distinct membrane constituents, and that guanine nucleotides apparently do not bind directly to the receptor molecules. Membrane-bound, solubilized and purified receptors were sensitive to inactivation by dithiothreitol, but not by N-ethylmaleimide, suggesting that receptors are at least partly constituted of protein molecules, with essential disulfide bonds."}
{"id": "PMID:226364", "title": "The relipidation of delipidated Na,K-ATPase. An analysis of complex formation with dioleoylphosphatidylcholine and with dioleoylphosphatidylethanolamine.", "content": "Enzymatically inactive, delipidated Na,K-ATPase from dogfish rectal glands was titrated with dioleoylphosphatidylcholine and with dioleoylphosphatidylethanolamine. The process of relipidation has the following characteristic properties. Enzymatic activities reappear independently of each other: first the phosphatase, then the ATPase. The properties of the phosphatase regenerated depend on the ratio of lipid/protein used; the ATPase seems to be independent of this ratio. The simplest model that is consistent with the above results and with the shapes of the titration curves, has the following requirements. Firstly, the enzyme is composed of two subunits that, as far as lipid binding is concerned, are identical and independent of each other. Secondly, lipid adds onto the enzyme as preformed clumps of 25 molecules of phosphatidylcholine or 18 molecules of phosphatidylethanolamine. Thirdly, each subunit binds two clumps of lipid, and binding shows positive cooperativity. Fourthly, when either subunit becomes saturated with lipid, the enzyme exhibits one form of phosphatase. Fifthly, when both subunits are saturated with lipid, the enzyme exhibits a second form of phosphatase and ATPase. The data and their analysis according to this model lead to the suggestion that Na,K-ATPase is a functional dimer, the interaction between subunits being influenced by the Na+ and K+ concentrations in the medium: K+ favouring the functional independence of the subunits and Na+ favouring their functional interaction.", "contents": "The relipidation of delipidated Na,K-ATPase. An analysis of complex formation with dioleoylphosphatidylcholine and with dioleoylphosphatidylethanolamine. Enzymatically inactive, delipidated Na,K-ATPase from dogfish rectal glands was titrated with dioleoylphosphatidylcholine and with dioleoylphosphatidylethanolamine. The process of relipidation has the following characteristic properties. Enzymatic activities reappear independently of each other: first the phosphatase, then the ATPase. The properties of the phosphatase regenerated depend on the ratio of lipid/protein used; the ATPase seems to be independent of this ratio. The simplest model that is consistent with the above results and with the shapes of the titration curves, has the following requirements. Firstly, the enzyme is composed of two subunits that, as far as lipid binding is concerned, are identical and independent of each other. Secondly, lipid adds onto the enzyme as preformed clumps of 25 molecules of phosphatidylcholine or 18 molecules of phosphatidylethanolamine. Thirdly, each subunit binds two clumps of lipid, and binding shows positive cooperativity. Fourthly, when either subunit becomes saturated with lipid, the enzyme exhibits one form of phosphatase. Fifthly, when both subunits are saturated with lipid, the enzyme exhibits a second form of phosphatase and ATPase. The data and their analysis according to this model lead to the suggestion that Na,K-ATPase is a functional dimer, the interaction between subunits being influenced by the Na+ and K+ concentrations in the medium: K+ favouring the functional independence of the subunits and Na+ favouring their functional interaction."}
{"id": "PMID:226365", "title": "Isolation of mitochondrial succinate: ubiquinone reductase, cytochrome c reductase and cytochrome c oxidase from Neurospora crassa using nonionic detergent.", "content": "The electron transfer complexes, succinate: ubiquinone reductase, ubiquinone: cytochrome c reductase, and cytochrome c: O2 oxidase were isolated from the mitochondrial membranes of Neurospora crassa by the following steps. Modification of the contents of the complexes in mitochondria by growing cells on chloramphenicol; solubilisation of the complexes by Triton X-100; affinity chromatography on immobilized cytochrome c and ion exchange and gel chromatography. Ubiquinone reductase was obtained in a monomeric form (Mr approximately 130 000) consisting of a flavin subunit (Mr 72 000) an iron-sulfur subunit (Mr 28 000) and a cytochrome b subunit (Mr probably 14 000). Cytochrome c reductase was obtained in a dimeric form (Mr approximately 550 000), the monomeric unit comprising the cytochromes b (Mr each 30 000), a cytochrome c1 (Mr 31 000), the iron-sulfur subunit (Mr 25 000), and six subunits without known prosthetic groups (Mr 9000, 11 000, 14 000, 45 000, 45 000, and 52 000). Cytochrome c oxidase was also isolated in a dimeric form (Mr approximately 320 000) comprising two copies each of seven subunits (Mr 9000, 12 000, 14 000, 18 000, 21 000, 29 000, and 40 000). The complexes were essentially free of phospholipid. Each bound one micelle of Triton X-100 (Mr approximately 90 000). After isolation, the bound Triton X-100 could be replaced by other nonionic detergents such as: alkylphenyl polyoxyethylene ethers, alkyl polyoxyethylene ethers and acyl polyoxyethylene sorbitan esters.", "contents": "Isolation of mitochondrial succinate: ubiquinone reductase, cytochrome c reductase and cytochrome c oxidase from Neurospora crassa using nonionic detergent. The electron transfer complexes, succinate: ubiquinone reductase, ubiquinone: cytochrome c reductase, and cytochrome c: O2 oxidase were isolated from the mitochondrial membranes of Neurospora crassa by the following steps. Modification of the contents of the complexes in mitochondria by growing cells on chloramphenicol; solubilisation of the complexes by Triton X-100; affinity chromatography on immobilized cytochrome c and ion exchange and gel chromatography. Ubiquinone reductase was obtained in a monomeric form (Mr approximately 130 000) consisting of a flavin subunit (Mr 72 000) an iron-sulfur subunit (Mr 28 000) and a cytochrome b subunit (Mr probably 14 000). Cytochrome c reductase was obtained in a dimeric form (Mr approximately 550 000), the monomeric unit comprising the cytochromes b (Mr each 30 000), a cytochrome c1 (Mr 31 000), the iron-sulfur subunit (Mr 25 000), and six subunits without known prosthetic groups (Mr 9000, 11 000, 14 000, 45 000, 45 000, and 52 000). Cytochrome c oxidase was also isolated in a dimeric form (Mr approximately 320 000) comprising two copies each of seven subunits (Mr 9000, 12 000, 14 000, 18 000, 21 000, 29 000, and 40 000). The complexes were essentially free of phospholipid. Each bound one micelle of Triton X-100 (Mr approximately 90 000). After isolation, the bound Triton X-100 could be replaced by other nonionic detergents such as: alkylphenyl polyoxyethylene ethers, alkyl polyoxyethylene ethers and acyl polyoxyethylene sorbitan esters."}
{"id": "PMID:226366", "title": "Enzymology of ubiquinone-utilizing electron transfer complexes in nonionic detergent.", "content": "The enzymology of isolated succinate: ubiquinone reductase and ubiquinone: cytochrome c reductase in nonionic detergents (alkyl polyoxyethylene derivatives) was studied. In the membrane the two multiprotein complexes and their hydrophobic substrates ubiquinone and dihydroubiquinone, are embedded in a common lipid bilayer. In detergent solutions the complexes are each inserted into micelles. Detergent micelles also serve as a solvent for the complexes hydrophobic substrates. As a consequence the isolated complexes are in a discontinuous phase with respect to their hydrophobic substrates and with respect to each other. Three types of assays were used. Firstly, single enzyme assays in which the hydrophobic substrates had to transfer from free micelles to the complex-bound micelles in order for enzyme reactions to occur. Secondly, assays in which the enzymic reactions were coupled to auxiliary nonenzymic reactions which rapidly converted the hydrophobic products back into substrates within the complex-bound micelle. Dichloroindophenol was used for the oxidation of dihydroubiquinone and dihydroduroquinone for the reduction of ubiquinone. Thirdly, assays in which the succinate: ubiquinone reductase reaction was coupled with the ubiquinone: cytochrome c reductase reaction. With the first type of assay, the kinetics of the substrate transfer reaction was dependent upon the type of detergent. In detergents with small polyoxyethylene head groups the transfer reactions were rate-limiting, and in detergents with large polyoxyethylene head groups the transfer reactions were fast and the enzymic reactions were rate-limiting...", "contents": "Enzymology of ubiquinone-utilizing electron transfer complexes in nonionic detergent. The enzymology of isolated succinate: ubiquinone reductase and ubiquinone: cytochrome c reductase in nonionic detergents (alkyl polyoxyethylene derivatives) was studied. In the membrane the two multiprotein complexes and their hydrophobic substrates ubiquinone and dihydroubiquinone, are embedded in a common lipid bilayer. In detergent solutions the complexes are each inserted into micelles. Detergent micelles also serve as a solvent for the complexes hydrophobic substrates. As a consequence the isolated complexes are in a discontinuous phase with respect to their hydrophobic substrates and with respect to each other. Three types of assays were used. Firstly, single enzyme assays in which the hydrophobic substrates had to transfer from free micelles to the complex-bound micelles in order for enzyme reactions to occur. Secondly, assays in which the enzymic reactions were coupled to auxiliary nonenzymic reactions which rapidly converted the hydrophobic products back into substrates within the complex-bound micelle. Dichloroindophenol was used for the oxidation of dihydroubiquinone and dihydroduroquinone for the reduction of ubiquinone. Thirdly, assays in which the succinate: ubiquinone reductase reaction was coupled with the ubiquinone: cytochrome c reductase reaction. With the first type of assay, the kinetics of the substrate transfer reaction was dependent upon the type of detergent. In detergents with small polyoxyethylene head groups the transfer reactions were rate-limiting, and in detergents with large polyoxyethylene head groups the transfer reactions were fast and the enzymic reactions were rate-limiting..."}
{"id": "PMID:226368", "title": "Membrane retrieval in epithelial cells of isolated thyroid follicles.", "content": "Follicles from rat and pig thyroid glands were isolated by digestion with collagenase. The epithelial cells of isolated follicles maintain their structural and functional polarity as shown by incorporation of 3H-leucine and autoradiography. To trace the fate of surface membrane, isolated follicles were opened, stimulated with thyrotropin and incubated for various time intervals with cationized ferritin (CF), uncharged dextran, native ferritin (NF), and latex spheres (0.5 mum in diameter) which were either pre-coated with CF or added together with CF. Uncharged dextran and native ferritin did not bind to the luminal cell membrane, were taken up in small amounts and accumulated in lysosomes; anionic NF was not found in Golgi cisternae in contrast to uncharged dextran which occassionally reached a few Golgi stacks. CF bound rapidly and in clusters to the luminal plasmalemma, preferentially to coated pits, was taken up by endocytosis, accumulated in lysosomes after 5 min and reached the Golgi cisternae after 30 min. Latex spheres were taken up by engulfment through fusion of microvilli and reached the lysosomes. CF particles coating the latex spheres may detach at this station and reach the Golgi cisternae. The findings show that the route of small tracers depends on the charge of the tracer, in agreement with results obtained by Farquhar [8]. Vesicles carrying NF can be traced to lysosomes only, whereas vesicles containing uncharged dextran or - more conspicuously -CF also fuse with Golgi membranes. Large tracers (latex beads) reach only the lysosomes, but CF taken up with them may move to Golgi cisternae.", "contents": "Membrane retrieval in epithelial cells of isolated thyroid follicles. Follicles from rat and pig thyroid glands were isolated by digestion with collagenase. The epithelial cells of isolated follicles maintain their structural and functional polarity as shown by incorporation of 3H-leucine and autoradiography. To trace the fate of surface membrane, isolated follicles were opened, stimulated with thyrotropin and incubated for various time intervals with cationized ferritin (CF), uncharged dextran, native ferritin (NF), and latex spheres (0.5 mum in diameter) which were either pre-coated with CF or added together with CF. Uncharged dextran and native ferritin did not bind to the luminal cell membrane, were taken up in small amounts and accumulated in lysosomes; anionic NF was not found in Golgi cisternae in contrast to uncharged dextran which occassionally reached a few Golgi stacks. CF bound rapidly and in clusters to the luminal plasmalemma, preferentially to coated pits, was taken up by endocytosis, accumulated in lysosomes after 5 min and reached the Golgi cisternae after 30 min. Latex spheres were taken up by engulfment through fusion of microvilli and reached the lysosomes. CF particles coating the latex spheres may detach at this station and reach the Golgi cisternae. The findings show that the route of small tracers depends on the charge of the tracer, in agreement with results obtained by Farquhar [8]. Vesicles carrying NF can be traced to lysosomes only, whereas vesicles containing uncharged dextran or - more conspicuously -CF also fuse with Golgi membranes. Large tracers (latex beads) reach only the lysosomes, but CF taken up with them may move to Golgi cisternae."}
{"id": "PMID:226369", "title": "Maintenance of Fc receptors in hybrid cell lines obtained by fusing mouse splenic macrophages with mouse myeloma cells.", "content": "Mouse splenic macrophages were fused with cells of the mouse myeloma line P3-X63-Ag8 in the presence of inactivated Sendai virus. Two continuously growing hybrid cell lines were established from fusion mixtures. These hybrid cell lines exhibited macrophage-like morphology and continued to express macrophage derived Fc receptor activity even after prolonged culture in vitro.", "contents": "Maintenance of Fc receptors in hybrid cell lines obtained by fusing mouse splenic macrophages with mouse myeloma cells. Mouse splenic macrophages were fused with cells of the mouse myeloma line P3-X63-Ag8 in the presence of inactivated Sendai virus. Two continuously growing hybrid cell lines were established from fusion mixtures. These hybrid cell lines exhibited macrophage-like morphology and continued to express macrophage derived Fc receptor activity even after prolonged culture in vitro."}
{"id": "PMID:226371", "title": "Studies on the central pressor activity of dibutyryl cyclic AMP.", "content": "The effects of the central administration (i.c.v.) of dibutyryl cyclic AMP (DBcAMP) on arterial blood pressure and heart rate were studied in the rat. The cyclic nucleotide produced a dose-dependent rise in blood pressure and an accompanying tachycardia. Maximal pressor effect of a single dose of DBcAMP (350 micrograms) was observed 25 min post injection and the duration of the response was 60 min. Chemical degeneration of central catecholaminergic neurons with 6-hydroxydopamine treatment abolished the pressor response to DBcAMP. Partial chemical degeneration of central serotonin pathways with 5,6-dihydroxytryptamine did not significantly alter the effect. The pressor activity of the cyclic nucleotide was attenuated by central administration of phentolamine. Spinal cord section at the C6-C7 level or peripheral chemical degeneration of catecholaminergic neurons combined with bilateral adrenalectomy abolished the pressor response to DBcAMP. It was concluded that the pressor response to i.c.v. administration of DBcAMP is mediated by central catecholaminergic pathways and is the result of an increase in efferent sympathetic outflow and release of catecholamines from the adrenal medulla.", "contents": "Studies on the central pressor activity of dibutyryl cyclic AMP. The effects of the central administration (i.c.v.) of dibutyryl cyclic AMP (DBcAMP) on arterial blood pressure and heart rate were studied in the rat. The cyclic nucleotide produced a dose-dependent rise in blood pressure and an accompanying tachycardia. Maximal pressor effect of a single dose of DBcAMP (350 micrograms) was observed 25 min post injection and the duration of the response was 60 min. Chemical degeneration of central catecholaminergic neurons with 6-hydroxydopamine treatment abolished the pressor response to DBcAMP. Partial chemical degeneration of central serotonin pathways with 5,6-dihydroxytryptamine did not significantly alter the effect. The pressor activity of the cyclic nucleotide was attenuated by central administration of phentolamine. Spinal cord section at the C6-C7 level or peripheral chemical degeneration of catecholaminergic neurons combined with bilateral adrenalectomy abolished the pressor response to DBcAMP. It was concluded that the pressor response to i.c.v. administration of DBcAMP is mediated by central catecholaminergic pathways and is the result of an increase in efferent sympathetic outflow and release of catecholamines from the adrenal medulla."}
{"id": "PMID:226372", "title": "Pharmacological activities of acetal derivatives of hemicholinium no. 3.", "content": "Acetal derivatives of hemicholinium no. 3 (HC-3) were synthesized and their chemical structures were confirmed by spectrophotometric evidence and elemental analysis. The acetals elicited a biphasic pattern of neuromuscular inhibition in the cat: (a) an immediate inhibition (early phase block) was judged to be curare-like as responses to acetylcholine (close i.a.) were abolished by acetal administration and reversal of inhibition was effected by neostigmine (25 micrograms/kg); (b) a slow, progressive inhibition of transmission (late phase block) was considered HC-3-like as it occurred only during high frequency stimulation and was antagonized by small doses of choline (1--3 mg/kg). In comparison to HC-3, significanlty greater curare-like activity was noted following acetal administration in vivo and in vitro. Mouse toxicity and cat nerve--muscle studies revealed the acetals to be HC-3-like but 1/2 to 1/3 as active as the parent compound. Cholinesterase inhibition by HC-3 and the acetals was low (I50 greater than 0.1 mM) and did not account for differences in activities. Acetal-elicited hypotension in the cat was attributed to postsynaptic ganglionic blockade and histamine release. Studies employing the 14C-(N-methyl) acetals furnished no evidence of the bioactivation (O-dealkylation) of the acetals to HC-3 in the cat in vivo or in cat liver in vitro. Chromatographic analysis afforded no evidence of molecular modifications of 14C-HC-3 or of the 14C-acetals in these systems.", "contents": "Pharmacological activities of acetal derivatives of hemicholinium no. 3. Acetal derivatives of hemicholinium no. 3 (HC-3) were synthesized and their chemical structures were confirmed by spectrophotometric evidence and elemental analysis. The acetals elicited a biphasic pattern of neuromuscular inhibition in the cat: (a) an immediate inhibition (early phase block) was judged to be curare-like as responses to acetylcholine (close i.a.) were abolished by acetal administration and reversal of inhibition was effected by neostigmine (25 micrograms/kg); (b) a slow, progressive inhibition of transmission (late phase block) was considered HC-3-like as it occurred only during high frequency stimulation and was antagonized by small doses of choline (1--3 mg/kg). In comparison to HC-3, significanlty greater curare-like activity was noted following acetal administration in vivo and in vitro. Mouse toxicity and cat nerve--muscle studies revealed the acetals to be HC-3-like but 1/2 to 1/3 as active as the parent compound. Cholinesterase inhibition by HC-3 and the acetals was low (I50 greater than 0.1 mM) and did not account for differences in activities. Acetal-elicited hypotension in the cat was attributed to postsynaptic ganglionic blockade and histamine release. Studies employing the 14C-(N-methyl) acetals furnished no evidence of the bioactivation (O-dealkylation) of the acetals to HC-3 in the cat in vivo or in cat liver in vitro. Chromatographic analysis afforded no evidence of molecular modifications of 14C-HC-3 or of the 14C-acetals in these systems."}
{"id": "PMID:226373", "title": "Direct chronotropic and inotropic responses to guanosine and five different guanine nucleotides in isolated perfused dog atria.", "content": "The effects of guanosine and of five guanine nucleotides on sinus rate and contractile force were investigated using the isolated, blood-perfused dog atrium preparation. Guanosine consistently induced a positive chronotropic and inotropic effect which was not suppressed by treatment with a potent beta-adrenoceptor blocking agent, carteolol. GMP, GDP and CTP induced a biphasic chronotropic and inotropic effect. The potencies for inducing the positive effects of GMP, GDP and GTP were almost the same. However, their rank order of potency for inducing negative effects was GTP greater than or equal to GDP greater than GMP. The negative responses to GTP were not inhibited by atropine. Cyclic GMP and dibutyryl cyclic GMP produced only slight negative chronotropic and inotropic effects but not consistently even at larger doses. The positive chronotropic and inotropic responses to norepinephrine were not modified by treatment with dibutyryl cyclic GMP.", "contents": "Direct chronotropic and inotropic responses to guanosine and five different guanine nucleotides in isolated perfused dog atria. The effects of guanosine and of five guanine nucleotides on sinus rate and contractile force were investigated using the isolated, blood-perfused dog atrium preparation. Guanosine consistently induced a positive chronotropic and inotropic effect which was not suppressed by treatment with a potent beta-adrenoceptor blocking agent, carteolol. GMP, GDP and CTP induced a biphasic chronotropic and inotropic effect. The potencies for inducing the positive effects of GMP, GDP and GTP were almost the same. However, their rank order of potency for inducing negative effects was GTP greater than or equal to GDP greater than GMP. The negative responses to GTP were not inhibited by atropine. Cyclic GMP and dibutyryl cyclic GMP produced only slight negative chronotropic and inotropic effects but not consistently even at larger doses. The positive chronotropic and inotropic responses to norepinephrine were not modified by treatment with dibutyryl cyclic GMP."}
{"id": "PMID:226375", "title": "Presynaptic GABA autoreceptors on GABAergic nerve endings of the rat substantia nigra.", "content": "The release of 3H-GABA evoked by exposure to 30 mM potassium during 1 min was found to calcium independent in the rat occipital cortex and calcium dependent in the substantia nigra. Exposure to either muscimol 1 microM or GABA 1 microM inhibited the potassium-evoked release of 3H-GABA from the substantia nigra but not from the occipital cortex. The inhibitory effect of muscimol 1 microM on the potassium-evoked release of 3H-GABA from the substantia nigra was significantly antagonized by picrotoxin 10 microM. Exposure to either 10 or 100 microM pricrotoxin alone did not affect the potassium-evoked release of 3H-GABA. These results are compatible with the presence of a negative feedback mechanism in bagaergic nerve terminals of the rat substantia nigra which is mediated by presynaptic GABA autoreceptors. In addition, these results emphasize the importance of the calcium-dependent nature of the release of the neurotransmitter for demonstrating the modulation of transmitter release through presynaptic receptors.", "contents": "Presynaptic GABA autoreceptors on GABAergic nerve endings of the rat substantia nigra. The release of 3H-GABA evoked by exposure to 30 mM potassium during 1 min was found to calcium independent in the rat occipital cortex and calcium dependent in the substantia nigra. Exposure to either muscimol 1 microM or GABA 1 microM inhibited the potassium-evoked release of 3H-GABA from the substantia nigra but not from the occipital cortex. The inhibitory effect of muscimol 1 microM on the potassium-evoked release of 3H-GABA from the substantia nigra was significantly antagonized by picrotoxin 10 microM. Exposure to either 10 or 100 microM pricrotoxin alone did not affect the potassium-evoked release of 3H-GABA. These results are compatible with the presence of a negative feedback mechanism in bagaergic nerve terminals of the rat substantia nigra which is mediated by presynaptic GABA autoreceptors. In addition, these results emphasize the importance of the calcium-dependent nature of the release of the neurotransmitter for demonstrating the modulation of transmitter release through presynaptic receptors."}
{"id": "PMID:226376", "title": "Muscarinic receptor binding in the rat adrenal medulla.", "content": "Muscarinic receptor binding sites are present in rat adrenal gland andare associated primarily with the medulla. A Scatchard analysis using the ligand [3H]-quinuclidinyl benzylate (eH-QNB) revealed a KD of 0.064 nM and a Bmax of 66 fmol/mg prot. Denervation of the adrenal gland had no significant effect on 3H-QNG binding. The presence of muscarinic receptor binding sites in the adrenal medulla is consistent with reports that muscarinic receptors play a role in the release of adrenal catecholamines and modulation of cycle 3',5'-guanosine monophosphate.", "contents": "Muscarinic receptor binding in the rat adrenal medulla. Muscarinic receptor binding sites are present in rat adrenal gland andare associated primarily with the medulla. A Scatchard analysis using the ligand [3H]-quinuclidinyl benzylate (eH-QNB) revealed a KD of 0.064 nM and a Bmax of 66 fmol/mg prot. Denervation of the adrenal gland had no significant effect on 3H-QNG binding. The presence of muscarinic receptor binding sites in the adrenal medulla is consistent with reports that muscarinic receptors play a role in the release of adrenal catecholamines and modulation of cycle 3',5'-guanosine monophosphate."}
{"id": "PMID:226377", "title": "The actions of enkephalins are not modified by the \"kininase-II\" inhibitor captopril.", "content": "The \"kininase-II\" (EC 3.4.15.1) inhibitor captopril in concentrations up to 10(-4) M did not affect the actions of enkephalins on the isolated electrically stimulated guinea-pig ileum. Captopril (100 mg/kg i.p.) in mice did not influence stimulation-produced analgesia and did not show analgesic properties. It is concluded that \"kininase-II\" is not involved in enkephalin catabolism, since the pharmacological actions of enkephalins were not enhanced after inhibition of the enzyme by captopril.", "contents": "The actions of enkephalins are not modified by the \"kininase-II\" inhibitor captopril. The \"kininase-II\" (EC 3.4.15.1) inhibitor captopril in concentrations up to 10(-4) M did not affect the actions of enkephalins on the isolated electrically stimulated guinea-pig ileum. Captopril (100 mg/kg i.p.) in mice did not influence stimulation-produced analgesia and did not show analgesic properties. It is concluded that \"kininase-II\" is not involved in enkephalin catabolism, since the pharmacological actions of enkephalins were not enhanced after inhibition of the enzyme by captopril."}
{"id": "PMID:226379", "title": "Binding to alpha-adrenergic receptors: differential pharmacological potencies and binding affinities of benzodioxanes.", "content": "We have compared the influence of a series of benzodioxane alpha-adrenergic antagonists on 3H-WB-4101 and 3H-clonidine binding to alpha-receptor sites in the brain and peripheral tissues with their pharmacological properties. The drug specificity of 3H-WB-4101 binding is quite similar in central and peripheral tissues. Pharmacological potencies of benzodioxanes at postsynaptic alpha-receptors in the rat vas deferens correlate with potencies at 3H-WB-4101 but not at 3H-clonidine binding sites. These findings suggest pharmacological effects of these drugs are mediated by \"alpha-1 postsynaptic receptors\" labeled by 3H-WB-4101. For several benzodioxanes absolute pharmacological potencies at postsynaptic alpha-receptors of the rat vas deferens are substantially less than their potencies at 3H-WB-4101 sites. The potencies of benzodioxane analogues at 3H-clinidine binding sites are similar to their pharmacological potencies at presynaptic autoreceptors in the rat vas deferens.", "contents": "Binding to alpha-adrenergic receptors: differential pharmacological potencies and binding affinities of benzodioxanes. We have compared the influence of a series of benzodioxane alpha-adrenergic antagonists on 3H-WB-4101 and 3H-clonidine binding to alpha-receptor sites in the brain and peripheral tissues with their pharmacological properties. The drug specificity of 3H-WB-4101 binding is quite similar in central and peripheral tissues. Pharmacological potencies of benzodioxanes at postsynaptic alpha-receptors in the rat vas deferens correlate with potencies at 3H-WB-4101 but not at 3H-clonidine binding sites. These findings suggest pharmacological effects of these drugs are mediated by \"alpha-1 postsynaptic receptors\" labeled by 3H-WB-4101. For several benzodioxanes absolute pharmacological potencies at postsynaptic alpha-receptors of the rat vas deferens are substantially less than their potencies at 3H-WB-4101 sites. The potencies of benzodioxane analogues at 3H-clinidine binding sites are similar to their pharmacological potencies at presynaptic autoreceptors in the rat vas deferens."}
{"id": "PMID:226380", "title": "Differential effect of potassium on the action of digoxin and digoxigenin in guinea-pig heart.", "content": "The effect of potassium on the binding of digoxin or digoxigenin to isolated Na+, K+-ATPase was compared with that of potassium on the positive inotropic action of the agents in guinea-pig hearts. The binding of digoxigenin to the enzyme in vitro was reduced to a greater extent by potassium than was the binding of digotoxin. The digoxigenin-induced increase in the force of contraction of left atrial preparations estimated at steady state was reduced at higher potassium concentrations. Potassium had a lesser effect when digoxin was used as the inotropic agent. In contrast, potassium concentrations. Potassium had a lesser effect when digoxin was used as the ininotropic agent. In contrast, potassium reduced the rate of development and also the rate of loss of the positive inotropic action of digoxin observed with left atrial and Langendorff preparations, respectively, to a greater extent than those of digoxigenin. The loss of the positive inotropic effect was more rapid with digoxigenin than with digoxin at each KCl concentration. These data support the contention that the extent of the interaction of digitalis with Na+,K+-ATPase determines the degree of the positive inotropic effect.", "contents": "Differential effect of potassium on the action of digoxin and digoxigenin in guinea-pig heart. The effect of potassium on the binding of digoxin or digoxigenin to isolated Na+, K+-ATPase was compared with that of potassium on the positive inotropic action of the agents in guinea-pig hearts. The binding of digoxigenin to the enzyme in vitro was reduced to a greater extent by potassium than was the binding of digotoxin. The digoxigenin-induced increase in the force of contraction of left atrial preparations estimated at steady state was reduced at higher potassium concentrations. Potassium had a lesser effect when digoxin was used as the inotropic agent. In contrast, potassium concentrations. Potassium had a lesser effect when digoxin was used as the ininotropic agent. In contrast, potassium reduced the rate of development and also the rate of loss of the positive inotropic action of digoxin observed with left atrial and Langendorff preparations, respectively, to a greater extent than those of digoxigenin. The loss of the positive inotropic effect was more rapid with digoxigenin than with digoxin at each KCl concentration. These data support the contention that the extent of the interaction of digitalis with Na+,K+-ATPase determines the degree of the positive inotropic effect."}
{"id": "PMID:226381", "title": "Effects of ACTH4-10 on synaptic transmission in frog sympathetic ganglion.", "content": "The influence of ACTH4-10, a behaviourally active fragment of adrenocorticotropic hormone (ACTH) devoid of endocrine activity, on synaptic transmission in the paravertebral sympathetic ganglion of the frog was investigated. Postsynaptic potentials evoked by electrical stimulation of pregnanglionic nerves were recorded using a sucrose gap method. Fast excitatory postsynaptic potentials (EPSPs), which are mediated via nicotinic cholinergic synapses, were not affected by 10(-6) M ACTH4-10. Application of ACTH4-10 in  a concentration as low as 10(-8) M for 60 min caused a marked augmentation of the amplitude of slow inhibitory postsynaptic potentials (IPSPs) which are mediated via dopaminergic synapses. The increase in amplitude developed gradually after a latency of 60--90 min and outlasted the application of the peptide. In addition, ACTH4-10 at 10(-6) M increased the hyperpolarising response of the ganglion to exogenous dopamine, as studied by a micro-application method. There was no significant effect of ACTH4-10 on the muscarinic cholinergic depolarising response of the ganglion towards exogenous acetylcholine. The behaviourally active vasopressin fragment DG-LVP (10(-6) M) had no effect on slow IPSPs. The results demonstrate that ACTH4-10 specifically affects slow synaptic inhibition in frog sympathetic ganglion, probably by acting upon the postsynaptic membrane. The possibility is discussed that ACTH4-10 affects one of the intermediate steps between dopaminergic receptor interaction and generation of the slow IPSP.", "contents": "Effects of ACTH4-10 on synaptic transmission in frog sympathetic ganglion. The influence of ACTH4-10, a behaviourally active fragment of adrenocorticotropic hormone (ACTH) devoid of endocrine activity, on synaptic transmission in the paravertebral sympathetic ganglion of the frog was investigated. Postsynaptic potentials evoked by electrical stimulation of pregnanglionic nerves were recorded using a sucrose gap method. Fast excitatory postsynaptic potentials (EPSPs), which are mediated via nicotinic cholinergic synapses, were not affected by 10(-6) M ACTH4-10. Application of ACTH4-10 in  a concentration as low as 10(-8) M for 60 min caused a marked augmentation of the amplitude of slow inhibitory postsynaptic potentials (IPSPs) which are mediated via dopaminergic synapses. The increase in amplitude developed gradually after a latency of 60--90 min and outlasted the application of the peptide. In addition, ACTH4-10 at 10(-6) M increased the hyperpolarising response of the ganglion to exogenous dopamine, as studied by a micro-application method. There was no significant effect of ACTH4-10 on the muscarinic cholinergic depolarising response of the ganglion towards exogenous acetylcholine. The behaviourally active vasopressin fragment DG-LVP (10(-6) M) had no effect on slow IPSPs. The results demonstrate that ACTH4-10 specifically affects slow synaptic inhibition in frog sympathetic ganglion, probably by acting upon the postsynaptic membrane. The possibility is discussed that ACTH4-10 affects one of the intermediate steps between dopaminergic receptor interaction and generation of the slow IPSP."}
{"id": "PMID:226382", "title": "The effects of chemical sympathectomy with 6-hydroxydopamine on alpha-adrenoceptor and muscarinic cholinoceptor binding in rat heart ventricle.", "content": "The specific binding of 3H-dihydroergocryptine to alpha-adrenoceptors in membranes from the heart ventricle of rats chemically denervated with 6-hydroxydopamine was significantly decreased in comparison with control animals. In contrast the muscarinic cholinoceptor binding of 3H-quinuclinidyl benzilate was unchanged after chemical sympathectomy. These results are interpreted as indicating that the muscarinic receptors are principally postsynaptic but that a significant proportion of the alpha-adrenoceptors are located on noradrenergic nerve terminals.", "contents": "The effects of chemical sympathectomy with 6-hydroxydopamine on alpha-adrenoceptor and muscarinic cholinoceptor binding in rat heart ventricle. The specific binding of 3H-dihydroergocryptine to alpha-adrenoceptors in membranes from the heart ventricle of rats chemically denervated with 6-hydroxydopamine was significantly decreased in comparison with control animals. In contrast the muscarinic cholinoceptor binding of 3H-quinuclinidyl benzilate was unchanged after chemical sympathectomy. These results are interpreted as indicating that the muscarinic receptors are principally postsynaptic but that a significant proportion of the alpha-adrenoceptors are located on noradrenergic nerve terminals."}
{"id": "PMID:226385", "title": "Friend virus production and heme synthesis in primary mouse spleen cell cultures.", "content": "A cell culture method has been developed in which spleen cells from Friend virus (FV) infected mice can be studied for virus production as well as erythroid differentiation. Primary spleen cell cultures from plethoric Balb/c mice were initiated at 24, 48 or 73 h after FV infection. These cells manifested a well-defined wave of heme synthesis at approximately 64, 48, or 23 h, respectively, of cell culture. Assays for spleen focus-forming virus (SFFV) and helper murine leukemia virus (MuLV-F) production in these cultures revealed that the peak rates of production of both viruses occurred at essentially the same time as the peaks of heme synthesis. The time at which the peaks of virus production and heme synthesis occurred in vitro was related to the time interval after infection (80-105 h) rather than the time at which the cells were placed in cell culture or the number of hours of cell culture. Medium change experiments suggested that the temporal relation between heme synthesis and virus production was an intrinsic feature of FVP infected cells in this in vitro system.", "contents": "Friend virus production and heme synthesis in primary mouse spleen cell cultures. A cell culture method has been developed in which spleen cells from Friend virus (FV) infected mice can be studied for virus production as well as erythroid differentiation. Primary spleen cell cultures from plethoric Balb/c mice were initiated at 24, 48 or 73 h after FV infection. These cells manifested a well-defined wave of heme synthesis at approximately 64, 48, or 23 h, respectively, of cell culture. Assays for spleen focus-forming virus (SFFV) and helper murine leukemia virus (MuLV-F) production in these cultures revealed that the peak rates of production of both viruses occurred at essentially the same time as the peaks of heme synthesis. The time at which the peaks of virus production and heme synthesis occurred in vitro was related to the time interval after infection (80-105 h) rather than the time at which the cells were placed in cell culture or the number of hours of cell culture. Medium change experiments suggested that the temporal relation between heme synthesis and virus production was an intrinsic feature of FVP infected cells in this in vitro system."}
{"id": "PMID:226386", "title": "Changes in oxygen radical scavenging by human blood cell lysates concurrent with viral infections.", "content": "The higher superoxide dismutase (SOD) levels found in human blood cells when Nitro Blue Tetrazolium (NBT) rather than Cytochrome C was used as the colorimetric detector of superoxide (O-2) was investigated. the NBT was found to react with oxygen radicals other than O-2, thus providing measurement of total oxygen radical scavenging ability. Also investigated was the biomodal distribution of SOD activity in lymphocytes and granulocytes from a randomly selected human populace. Human lymphocytes rapidly increased their SOD activity by two- to four-fold during respiratory viral distress. The response to certain infections was probably responsible for the bimodal distribution of SOD activity in the general populace. It was concluded that the chemical events that prepare lymphocytes and granulocytes for their role in defense against infections begin long before these cells are sequestered from circulation by the infections.", "contents": "Changes in oxygen radical scavenging by human blood cell lysates concurrent with viral infections. The higher superoxide dismutase (SOD) levels found in human blood cells when Nitro Blue Tetrazolium (NBT) rather than Cytochrome C was used as the colorimetric detector of superoxide (O-2) was investigated. the NBT was found to react with oxygen radicals other than O-2, thus providing measurement of total oxygen radical scavenging ability. Also investigated was the biomodal distribution of SOD activity in lymphocytes and granulocytes from a randomly selected human populace. Human lymphocytes rapidly increased their SOD activity by two- to four-fold during respiratory viral distress. The response to certain infections was probably responsible for the bimodal distribution of SOD activity in the general populace. It was concluded that the chemical events that prepare lymphocytes and granulocytes for their role in defense against infections begin long before these cells are sequestered from circulation by the infections."}
{"id": "PMID:226388", "title": "Mechanisms of compensation for vestibular deficits in the frog. I. Modification of the excitatory commissural system.", "content": "In hemilabyrinthectomized frogs excitatory responses of central vestibular neurons to electrical stimulation of the remaining vestibular nerve were recorded extra- and intracellulary at different stages (0, 3, and 60 days) after the operation. The output pattern of ipsilateral vestibular neurons sending an axon across the midline via the vestibular commissure to the deafferented nucleus did not change postoperatively. The synaptic efficacy of these commissural axons ending on partially deafferented vestibular neurons on the lesioned side increased with time. This enhanced synaptic potency was associated with a shortening in time to peak and duration and an increase in amplitude of the evoked EPSPs. As a result most vestibular neurons were readily excited by single shock stimulation of the contralateral vestibular nerve, a finding which was rarely observed in control animals. These plastic changes are explained by the assumption of reactive synaptogenesis. The consequences of this modification for the readjustment of static and dynamic vestibular reflexes are discussed.", "contents": "Mechanisms of compensation for vestibular deficits in the frog. I. Modification of the excitatory commissural system. In hemilabyrinthectomized frogs excitatory responses of central vestibular neurons to electrical stimulation of the remaining vestibular nerve were recorded extra- and intracellulary at different stages (0, 3, and 60 days) after the operation. The output pattern of ipsilateral vestibular neurons sending an axon across the midline via the vestibular commissure to the deafferented nucleus did not change postoperatively. The synaptic efficacy of these commissural axons ending on partially deafferented vestibular neurons on the lesioned side increased with time. This enhanced synaptic potency was associated with a shortening in time to peak and duration and an increase in amplitude of the evoked EPSPs. As a result most vestibular neurons were readily excited by single shock stimulation of the contralateral vestibular nerve, a finding which was rarely observed in control animals. These plastic changes are explained by the assumption of reactive synaptogenesis. The consequences of this modification for the readjustment of static and dynamic vestibular reflexes are discussed."}
{"id": "PMID:226394", "title": "Studies on the late-pre-beta-lipoprotein of human serum.", "content": "Very low density lipoprotein (VLDL) isolated from 3 healthy normolipidaemic subjects had a raised VLDL cholesterol to triglyceride ratio. The VLDL fractions gave 2 pre-beta-bands on agarose gel electrophoresis. Family study of the subjects appears to indicate sex linkage of this trait and a possible polygenic type of inheritance.", "contents": "Studies on the late-pre-beta-lipoprotein of human serum. Very low density lipoprotein (VLDL) isolated from 3 healthy normolipidaemic subjects had a raised VLDL cholesterol to triglyceride ratio. The VLDL fractions gave 2 pre-beta-bands on agarose gel electrophoresis. Family study of the subjects appears to indicate sex linkage of this trait and a possible polygenic type of inheritance."}
{"id": "PMID:226395", "title": "Mechanisms of heterotypic immunity against canine distemper.", "content": "Hep-2 cells infected with measles virus (MV) for as short as 6 h became refractory to superinfection with canine distemper virus (CDV) but not to vesicular stomatitis virus (VSV). The exact mechanism of such interference is unknown but probably occurs after virus attachment and penetration. These results verify the suggestion that virus interference may be a mechanism of heterotypic protection against canine distemper.", "contents": "Mechanisms of heterotypic immunity against canine distemper. Hep-2 cells infected with measles virus (MV) for as short as 6 h became refractory to superinfection with canine distemper virus (CDV) but not to vesicular stomatitis virus (VSV). The exact mechanism of such interference is unknown but probably occurs after virus attachment and penetration. These results verify the suggestion that virus interference may be a mechanism of heterotypic protection against canine distemper."}
{"id": "PMID:226396", "title": "Inhibition of hepatic Na +, K + -adenosinetriphosphatase in taurolithocholate-induced cholestasis in the rat.", "content": "Na +, K + -adenosinetriphosphatase (Na +, K + -ATPase) activity was decreased in liver plasma membranes from rats in which cholestasis had been induced by i.v. administration of sodium taurolithocholate (5 mumoles/100 g b. wt). Incubation of liver plasma membranes with taurolithocholate (10--1300 muM) caused significant and dose dependent reductions of Na +, K + -ATPase activity at taurolithocholate concentrations above 100 muM. These findings lend support to the hypothesis that cholestasis induced by monohydroxy bile acids is at least partially the result of an inhibition of hepatic Na +, K + -ATPase activity.", "contents": "Inhibition of hepatic Na +, K + -adenosinetriphosphatase in taurolithocholate-induced cholestasis in the rat. Na +, K + -adenosinetriphosphatase (Na +, K + -ATPase) activity was decreased in liver plasma membranes from rats in which cholestasis had been induced by i.v. administration of sodium taurolithocholate (5 mumoles/100 g b. wt). Incubation of liver plasma membranes with taurolithocholate (10--1300 muM) caused significant and dose dependent reductions of Na +, K + -ATPase activity at taurolithocholate concentrations above 100 muM. These findings lend support to the hypothesis that cholestasis induced by monohydroxy bile acids is at least partially the result of an inhibition of hepatic Na +, K + -ATPase activity."}
{"id": "PMID:226397", "title": "The effect of halothane on the action of alcuronium in the dog.", "content": "The effect of halothane on the action of alcuronium on neuromuscular transmission was studied in the intact dog. Electrical and mechanical evoked responses from stimulation of the ulnar nerve were recorded. The administration of 0.5% halothane prolonged the duration of action of alcuronium by about 50%.", "contents": "The effect of halothane on the action of alcuronium in the dog. The effect of halothane on the action of alcuronium on neuromuscular transmission was studied in the intact dog. Electrical and mechanical evoked responses from stimulation of the ulnar nerve were recorded. The administration of 0.5% halothane prolonged the duration of action of alcuronium by about 50%."}
{"id": "PMID:226398", "title": "ACTH-induced hyperalgesia in rats.", "content": "The injection of ACTH 1--24 into the cerebral ventricles in rats markedly reduces the reaction time in the hot-plate test and the nociception threshold in the tail-stimulation test. Morphine antagonizes and naloxone potentiates this hyperalgesic effect of ACTH. It is proposed that ACTH peptides play a physiological role in nociception.", "contents": "ACTH-induced hyperalgesia in rats. The injection of ACTH 1--24 into the cerebral ventricles in rats markedly reduces the reaction time in the hot-plate test and the nociception threshold in the tail-stimulation test. Morphine antagonizes and naloxone potentiates this hyperalgesic effect of ACTH. It is proposed that ACTH peptides play a physiological role in nociception."}
{"id": "PMID:226399", "title": "The inhibitory effect of paraquat on histamine and isoproterenol induced changes of cyclic nucleotides in rat lung slices.", "content": "The incubation of rat lung slices with paraquat ion (10(-4) M) had no effect on cAMP and cGMP levels of the rat lung slices. The preincubation with the same concentration of paraquat inhibited the cAMP elevating effect of histamine (10(-5) M) and isoproterenol (10(-5) M) and reduced the cGMP level to approximately 50% of the level obtained without preincubation with paraquat.", "contents": "The inhibitory effect of paraquat on histamine and isoproterenol induced changes of cyclic nucleotides in rat lung slices. The incubation of rat lung slices with paraquat ion (10(-4) M) had no effect on cAMP and cGMP levels of the rat lung slices. The preincubation with the same concentration of paraquat inhibited the cAMP elevating effect of histamine (10(-5) M) and isoproterenol (10(-5) M) and reduced the cGMP level to approximately 50% of the level obtained without preincubation with paraquat."}
{"id": "PMID:226400", "title": "[Tercuronium, a new nondepolarizing myorelaxant with high activity and selective action].", "content": "Tercuronium is p',p\"-bis-triethylammonium-p-terphenyl dibenzosulfonate. As a curarelike agent tercuronium is 4--8 times as potent as (+)-tubocurarine. The time of the development and lasting of the blocking effect of tercuronium is approximately the same as that of (+)-tubocurarine. In a blocking dose tercuronium does not exert any effect either on the vegetative ganglia or arterial blood pressure. Partial blocking of the transmission through the vegetative ganglia as well as an insignificant and short-term drop of arterial blood pressure are recorded after intravenous injection of 10 myoparalytic doses of tercuronium. The antagonism of neostigmine against tercuronium was more pronounced than against (+)-tubocurarine, pancuronium and gallamine.", "contents": "[Tercuronium, a new nondepolarizing myorelaxant with high activity and selective action]. Tercuronium is p',p\"-bis-triethylammonium-p-terphenyl dibenzosulfonate. As a curarelike agent tercuronium is 4--8 times as potent as (+)-tubocurarine. The time of the development and lasting of the blocking effect of tercuronium is approximately the same as that of (+)-tubocurarine. In a blocking dose tercuronium does not exert any effect either on the vegetative ganglia or arterial blood pressure. Partial blocking of the transmission through the vegetative ganglia as well as an insignificant and short-term drop of arterial blood pressure are recorded after intravenous injection of 10 myoparalytic doses of tercuronium. The antagonism of neostigmine against tercuronium was more pronounced than against (+)-tubocurarine, pancuronium and gallamine."}
{"id": "PMID:226420", "title": "[Nature of the hyperpotassic composition of the medium surrounding individual tissue mechanoreceptors].", "content": "The ouabain effect on potassium concentration in the Pacini corpuscle fluid was studied using continuous perfusion of cat's mesenteric receptors with ouabain in Ringer's bicarbonate solution. To check the solution penetration into the corpuscles, Na36Cl and (G-3H)-ouabain were used. 2 . 10(-2) mM ouabain reduced (K+) in corpuscle fluid. The high potassium concentration in Pacini corpuscle fluid seems to be due to Na+--K+-ATPase system.", "contents": "[Nature of the hyperpotassic composition of the medium surrounding individual tissue mechanoreceptors]. The ouabain effect on potassium concentration in the Pacini corpuscle fluid was studied using continuous perfusion of cat's mesenteric receptors with ouabain in Ringer's bicarbonate solution. To check the solution penetration into the corpuscles, Na36Cl and (G-3H)-ouabain were used. 2 . 10(-2) mM ouabain reduced (K+) in corpuscle fluid. The high potassium concentration in Pacini corpuscle fluid seems to be due to Na+--K+-ATPase system."}
{"id": "PMID:226421", "title": "[Adrenergic mechanisms of changes in the resistance and volume vessels of the small intestine in the presence of a reduced volume of circulating blood].", "content": "In humorally isolated small intestine, the 10--20%--decrease in the perfusing blood volume against the background of augmented vascular resistance of the small intestine, induces different shifts of the latter's vascular capacitance. At the blockade of small intestine's beta--adrenoreceptors the decrease does not practically tell on the character of shifts in the intestine's resistance and capacitance while the blockade of alpha--adrenoreceptors abolishes the augmentation of these parameters.", "contents": "[Adrenergic mechanisms of changes in the resistance and volume vessels of the small intestine in the presence of a reduced volume of circulating blood]. In humorally isolated small intestine, the 10--20%--decrease in the perfusing blood volume against the background of augmented vascular resistance of the small intestine, induces different shifts of the latter's vascular capacitance. At the blockade of small intestine's beta--adrenoreceptors the decrease does not practically tell on the character of shifts in the intestine's resistance and capacitance while the blockade of alpha--adrenoreceptors abolishes the augmentation of these parameters."}
{"id": "PMID:226423", "title": "[Adrenergic regulation of thermogenesis in Siberian lemmings].", "content": "Siberian lemmings seem to have lesser noradrenaline (NA) calorigenic action and higher beta-adrenergic \"asymmetry\" of catecholamine calorigenic effects than the cold- and warmth-adapted laboratory rodents. Selective inhibition of catecholamine effects by beta-adrenoblocking drug propranolol, obvious potentiation of NA effect by caffeine, and compensatory increasing of thermoregulatory musclar contractile activity during the blockade of betaadrenoreceptors under cooling suggest the domineering of betaadrenergic mechanisms of thermogenesis in siberian lemmings and their high thermoregulatory lability.", "contents": "[Adrenergic regulation of thermogenesis in Siberian lemmings]. Siberian lemmings seem to have lesser noradrenaline (NA) calorigenic action and higher beta-adrenergic \"asymmetry\" of catecholamine calorigenic effects than the cold- and warmth-adapted laboratory rodents. Selective inhibition of catecholamine effects by beta-adrenoblocking drug propranolol, obvious potentiation of NA effect by caffeine, and compensatory increasing of thermoregulatory musclar contractile activity during the blockade of betaadrenoreceptors under cooling suggest the domineering of betaadrenergic mechanisms of thermogenesis in siberian lemmings and their high thermoregulatory lability."}
{"id": "PMID:226424", "title": "[The characterization of nuclear triiodo-L-thyronine receptors of rabbit liver (author's transl)].", "content": "The binding characteristics and physical properties of the nuclear receptors of rabbit liver were studied. The receptors were extracted with 0.4M KCl from purified hepatic nuclei and were incubated with increasing doses of 125I-triiodo-L-thyronine (L-T3) and stable L-T3 for 2 hours at 20 degrees C. Scatchard analyses indicated that the association constant (Ka) of the nuclear receptors was 1.5 X 10(10)M-1, and that maximal binding capacity was about 0.12 pmol T3 per 1 ml of nuclear extract, equivalent to 1 g of liver or 0.2 pmol T3 per mg of protein of the nuclear extracts. The nuclear binding sites were specific for L-T3. When compared by the molar concentrations of hormone analogues required to produce 50% inhibition of L-T3 binding, the relative binding affinities of triiodothyroacetic acid (Triac), D-T3, L-T4 and D-T4 were, respectively, 1/2, 1/4, 1/50 and 1/170 of L-T3. The binding affinity of Triac for the isolated hepatic nuclei was also nearly half that of L-T3. Furthermore, to displace radioactive Triac from the binding sites, Triac was half as effective as L-T3. The molecular weight of the nuclear receptors was estimated to be about 40000 to 45000 by the elution profiles from a Sephadex G-100 column, and the sedimentation coefficient was slightly less than 4S on sucrose density gradient centrifugations. Both elution profiles from DEAE- and ECTEOLA- cellulose columns with a linear KCl gradient showed a sharp, narrow peak of radioactive T3 at about 0.15 to 0.2M KCl. The results obtained with rabbit liver were similar to those reported previously in rat liver except for the relative binding affinity for Triac. It is possible that this discrepancy may be due to a species-related difference.", "contents": "[The characterization of nuclear triiodo-L-thyronine receptors of rabbit liver (author's transl)]. The binding characteristics and physical properties of the nuclear receptors of rabbit liver were studied. The receptors were extracted with 0.4M KCl from purified hepatic nuclei and were incubated with increasing doses of 125I-triiodo-L-thyronine (L-T3) and stable L-T3 for 2 hours at 20 degrees C. Scatchard analyses indicated that the association constant (Ka) of the nuclear receptors was 1.5 X 10(10)M-1, and that maximal binding capacity was about 0.12 pmol T3 per 1 ml of nuclear extract, equivalent to 1 g of liver or 0.2 pmol T3 per mg of protein of the nuclear extracts. The nuclear binding sites were specific for L-T3. When compared by the molar concentrations of hormone analogues required to produce 50% inhibition of L-T3 binding, the relative binding affinities of triiodothyroacetic acid (Triac), D-T3, L-T4 and D-T4 were, respectively, 1/2, 1/4, 1/50 and 1/170 of L-T3. The binding affinity of Triac for the isolated hepatic nuclei was also nearly half that of L-T3. Furthermore, to displace radioactive Triac from the binding sites, Triac was half as effective as L-T3. The molecular weight of the nuclear receptors was estimated to be about 40000 to 45000 by the elution profiles from a Sephadex G-100 column, and the sedimentation coefficient was slightly less than 4S on sucrose density gradient centrifugations. Both elution profiles from DEAE- and ECTEOLA- cellulose columns with a linear KCl gradient showed a sharp, narrow peak of radioactive T3 at about 0.15 to 0.2M KCl. The results obtained with rabbit liver were similar to those reported previously in rat liver except for the relative binding affinity for Triac. It is possible that this discrepancy may be due to a species-related difference."}
{"id": "PMID:226425", "title": "[Increased liver nuclear triiodothyronine-receptors associated with mitochondrial alpha-glycerophosphate dehydrogenase activity in hyperthyroid rats (author's transl)].", "content": "The effects of triiodothyronine (T3) on binding characteristics of nuclear T3-receptors were examined in rats. The T3-receptors were extracted by 0.4M KCl from the liver nuclei isolated from the following 3 groups of rats: (1) thyroidectomized, (2) thyroidectomized and treated with 230 ng T3/100 g body weight/day for 3 days, and (3) thyroidectomized and treated with 40 micrograms T3/100 g body weight/day for 3 days. Their association constant (Ka) and maximal binding capacity (Cmax) for T3 were determined by Scatchard analyses with and without correction for endogenous T3. The amount of endogenous T3 bound to the nuclear extracts was estimated on the basis of a specific activity of [125I]-T3 injected 2 hours before sacrifice. It was demonstrated that Cmax values corrected for the endogenous T3 were 2.5 times greater in severely hyperthyroid than in hypothyroid rats. By contrast, corrected values for Ka remained unchanged in all 3 groups of rats, although uncorrected values were apparently decreased in the severely hyperthyroid rats. Validity of the correction was supported by the in vitro experiments preincubated with stable T3. The yields of nuclear protein-125I-T3 complex in the procedure of extraction and the contents of DNA per g of liver were nearly the same in the 3 groups. The increase in Cmax of the nuclear receptors was directly related to mitochondrial alpha-glycerophosphate dehydrogenase activity. The results obtained indicate that the Cmax of nuclear T3-receptors is increased in a severely hyperthyroid state, related to hormonal action, and that the correction for endogenous T3 is essential for an accurate estimation of Ka and Cmax.", "contents": "[Increased liver nuclear triiodothyronine-receptors associated with mitochondrial alpha-glycerophosphate dehydrogenase activity in hyperthyroid rats (author's transl)]. The effects of triiodothyronine (T3) on binding characteristics of nuclear T3-receptors were examined in rats. The T3-receptors were extracted by 0.4M KCl from the liver nuclei isolated from the following 3 groups of rats: (1) thyroidectomized, (2) thyroidectomized and treated with 230 ng T3/100 g body weight/day for 3 days, and (3) thyroidectomized and treated with 40 micrograms T3/100 g body weight/day for 3 days. Their association constant (Ka) and maximal binding capacity (Cmax) for T3 were determined by Scatchard analyses with and without correction for endogenous T3. The amount of endogenous T3 bound to the nuclear extracts was estimated on the basis of a specific activity of [125I]-T3 injected 2 hours before sacrifice. It was demonstrated that Cmax values corrected for the endogenous T3 were 2.5 times greater in severely hyperthyroid than in hypothyroid rats. By contrast, corrected values for Ka remained unchanged in all 3 groups of rats, although uncorrected values were apparently decreased in the severely hyperthyroid rats. Validity of the correction was supported by the in vitro experiments preincubated with stable T3. The yields of nuclear protein-125I-T3 complex in the procedure of extraction and the contents of DNA per g of liver were nearly the same in the 3 groups. The increase in Cmax of the nuclear receptors was directly related to mitochondrial alpha-glycerophosphate dehydrogenase activity. The results obtained indicate that the Cmax of nuclear T3-receptors is increased in a severely hyperthyroid state, related to hormonal action, and that the correction for endogenous T3 is essential for an accurate estimation of Ka and Cmax."}
{"id": "PMID:226426", "title": "[Sequential changes in the nuclear triiodothyronine receptors and mitochondrial alpha-glycerophosphate dehydrogenase activity after the administration of triiodothyronine (author's transl)].", "content": "The dynamics of the induction of nuclear triiodothyronine (T3)-receptors and mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD) were studied in rat liver after a single injection of a large amount of T3. The maximal binding capacity (Cmax) and association constant (Ka) of the nuclear receptors were determined by Scatchard analyses with and without correction for endogenous T3 measured by radioimmunoassay. It was demonstrated that the administration of T3 induced sequential increases in the number of nuclear T3-receptors and alpha-GPD activity in the liver. The nuclear receptors were rapidly increased to 2.5 times the hypothyroid level and thereafter decreased with a half-life of about 2 days. A parallel change in alpha-GPD activity was noted after a lag period. The total amount of extracted nuclear proteins in the liver was increased 3 days after the administration of T3. It seems likely, therefore, that the T3-induced increase in nuclear receptors is responsible, at least in part, for the induction of this enzyme. The possibility is also suggested that the nuclear receptors may be a nonhistone protein selectively synthesized in an early stage of the hormonal stimulation. Following the injection of T3, marked changes in apparent Ka were seen when no correction was made for the amount of endogenous T3 bound to the extracted nuclear proteins. With the correction, however, Ka remained the same despite the changes in the nuclear receptors and enzyme activity. The results obtained provide further evidence for the hormonal modulation of the nuclear receptors which is closely linked with the hormonal effect.", "contents": "[Sequential changes in the nuclear triiodothyronine receptors and mitochondrial alpha-glycerophosphate dehydrogenase activity after the administration of triiodothyronine (author's transl)]. The dynamics of the induction of nuclear triiodothyronine (T3)-receptors and mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD) were studied in rat liver after a single injection of a large amount of T3. The maximal binding capacity (Cmax) and association constant (Ka) of the nuclear receptors were determined by Scatchard analyses with and without correction for endogenous T3 measured by radioimmunoassay. It was demonstrated that the administration of T3 induced sequential increases in the number of nuclear T3-receptors and alpha-GPD activity in the liver. The nuclear receptors were rapidly increased to 2.5 times the hypothyroid level and thereafter decreased with a half-life of about 2 days. A parallel change in alpha-GPD activity was noted after a lag period. The total amount of extracted nuclear proteins in the liver was increased 3 days after the administration of T3. It seems likely, therefore, that the T3-induced increase in nuclear receptors is responsible, at least in part, for the induction of this enzyme. The possibility is also suggested that the nuclear receptors may be a nonhistone protein selectively synthesized in an early stage of the hormonal stimulation. Following the injection of T3, marked changes in apparent Ka were seen when no correction was made for the amount of endogenous T3 bound to the extracted nuclear proteins. With the correction, however, Ka remained the same despite the changes in the nuclear receptors and enzyme activity. The results obtained provide further evidence for the hormonal modulation of the nuclear receptors which is closely linked with the hormonal effect."}
{"id": "PMID:226427", "title": "[In vivo and in vitro studies on 18-hydroxy-11-deoxycorticosterone and 18-hydroxycorticosterone in normal subjects and in those with various adrenocortical disorders (author's transl)].", "content": "Simultaneous measurement of 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) and 18-hydroxycorticosterone (18-OH-B) in the peripheral plasma was carried out on normal subjects and in patients with adrenocortical disorders. The mean plasma levels of 18-OH-DOC at 0800h in normal males and in the follicular and luteal phases of normal females were 8.2 +/- 3.9 ng/100 ml (Mean +/- SD), 7.8 +/- 2.6 ng/100ml and 11.5 +/- 2.8 ng/100ml, respectively. The corresponding levels of 18-OH-B in normal males and in the follicular and luteal phases of normal females were 10.3 +/- 4.2 ng/100ml, 12.4 +/- 4.5 ng/100ml and 13.8 +/- 4.1 ng/100ml, respectively. No differences between the sexes nor the phases of the menstrual cycle were confirmed. ACTH stimulation increased plasma concentrations of 18-OH-DOC and 18-OH-B by 5.1 and 4.4 times respectively, while dexamethasone markedly decreased these 2 steroids. An upright posture increased these steroids significantly. In patients with Cushing syndrome, plasma levels of these 2 steroids were rarely high in cases with adrenocortical hyperplasia and adrenocortical carcinoma, while they were usually within the normal range in adrenocortical adenoma. These 2 steroid levels were increased in primary aldosteronism, idiopathic hyperaldosteronism and congenital 17 alpha-hydroxylase deficiency. They were decreased in Addison's disease and the salt-loosing type of congenital 21 alpha-hydroxylase deficiency. Patients with congenital 21 alpha-hydroxylase deficiency (simple form) showed elevated levels of 18-OH-DOC and normal levels of 18-OH-B. In vitro production of 18-OH-DOC and 18-OH-B was studied by tissue slices of the normal adrenal cortex, adrenocortical carcinoma causing Cushing syndrome, aldosteronoma and nodular hyperplasia with hyperaldosteronism. In the normal adrenal cortex, the mean production rates of 18-OH-DOC and 18-OH-B were 31 and 26 ng/g tissue/hr, respectively. ACTH and angiotensin II significantly increased the production of both 18-OH-DOC and 18-OH-B. In adrenocortical carcinoma, the production of these steroids was markedly diminished and not stimulated with either ACTH or angiotensin II. Aldosteronoma tissue produced these 2 steroids 20 to 40 times that of the normal adrenal tissue and was significantly increased with the addition of ACTH and angiotensin II. Nodular hyperplasia with hyperaldosteronism produced much 18-OH-DOC and 18-OH-B, but did not respond to ACTH and angiotensin II.", "contents": "[In vivo and in vitro studies on 18-hydroxy-11-deoxycorticosterone and 18-hydroxycorticosterone in normal subjects and in those with various adrenocortical disorders (author's transl)]. Simultaneous measurement of 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) and 18-hydroxycorticosterone (18-OH-B) in the peripheral plasma was carried out on normal subjects and in patients with adrenocortical disorders. The mean plasma levels of 18-OH-DOC at 0800h in normal males and in the follicular and luteal phases of normal females were 8.2 +/- 3.9 ng/100 ml (Mean +/- SD), 7.8 +/- 2.6 ng/100ml and 11.5 +/- 2.8 ng/100ml, respectively. The corresponding levels of 18-OH-B in normal males and in the follicular and luteal phases of normal females were 10.3 +/- 4.2 ng/100ml, 12.4 +/- 4.5 ng/100ml and 13.8 +/- 4.1 ng/100ml, respectively. No differences between the sexes nor the phases of the menstrual cycle were confirmed. ACTH stimulation increased plasma concentrations of 18-OH-DOC and 18-OH-B by 5.1 and 4.4 times respectively, while dexamethasone markedly decreased these 2 steroids. An upright posture increased these steroids significantly. In patients with Cushing syndrome, plasma levels of these 2 steroids were rarely high in cases with adrenocortical hyperplasia and adrenocortical carcinoma, while they were usually within the normal range in adrenocortical adenoma. These 2 steroid levels were increased in primary aldosteronism, idiopathic hyperaldosteronism and congenital 17 alpha-hydroxylase deficiency. They were decreased in Addison's disease and the salt-loosing type of congenital 21 alpha-hydroxylase deficiency. Patients with congenital 21 alpha-hydroxylase deficiency (simple form) showed elevated levels of 18-OH-DOC and normal levels of 18-OH-B. In vitro production of 18-OH-DOC and 18-OH-B was studied by tissue slices of the normal adrenal cortex, adrenocortical carcinoma causing Cushing syndrome, aldosteronoma and nodular hyperplasia with hyperaldosteronism. In the normal adrenal cortex, the mean production rates of 18-OH-DOC and 18-OH-B were 31 and 26 ng/g tissue/hr, respectively. ACTH and angiotensin II significantly increased the production of both 18-OH-DOC and 18-OH-B. In adrenocortical carcinoma, the production of these steroids was markedly diminished and not stimulated with either ACTH or angiotensin II. Aldosteronoma tissue produced these 2 steroids 20 to 40 times that of the normal adrenal tissue and was significantly increased with the addition of ACTH and angiotensin II. Nodular hyperplasia with hyperaldosteronism produced much 18-OH-DOC and 18-OH-B, but did not respond to ACTH and angiotensin II."}
{"id": "PMID:226438", "title": "Early effects of thyroidectomy and triiodothyronine administration on rat-liver mitochondria.", "content": "This work was undertaken to study the action exerted by thyroid hormones on mitochondria. By day 6 after thyroidectomy, the respective activities of two inner-membrane enzymes--succinate and beta-hydroxybutyrate cytochrome c reductases--had already dropped by 32 and 50%, whereas, in the outer membrane, the activity of rotenone-insensitive NADH-cytochrome c reductase did not change significantly. The decrease in the activity of the inner-membrane enzymes closely followed the disappearance of T3 and T4 from serum. 10 h after administration of 25 micrograms/100 g T3 to thyroidectomized rats, the activity of succinate and beta-hydroxybutyrate cytochrome c reductases and the oxygen consumption rate with succinate or beta-hydroxybutyrate were significantly increased, while, in the outer membrane, the activity of monoamine oxidase and rotenone-insensitive NADH-cytochrome c reductase remained unchanged. In the thyroidectomized rat, L-[3H]leucine incorporation in vivo is diminished in all the liver mitochondrial proteins, and especially in two constituents of MW 19 000 and 28 000. The radioactivity of these two components is also decreased in the normal rat treated with chloramphenicol, a specific inhibitor of mitochondrial protein synthesis. L-[14C]leucine incorporation in isolated liver mitochondria was significantly increased in the thyroidectomized rat, 10 h after T3 treatment. Thus, thyroid hormones have an early and preferential action on the mitochondrial protein synthesizing system and on the inner-membrane enzyme activities.", "contents": "Early effects of thyroidectomy and triiodothyronine administration on rat-liver mitochondria. This work was undertaken to study the action exerted by thyroid hormones on mitochondria. By day 6 after thyroidectomy, the respective activities of two inner-membrane enzymes--succinate and beta-hydroxybutyrate cytochrome c reductases--had already dropped by 32 and 50%, whereas, in the outer membrane, the activity of rotenone-insensitive NADH-cytochrome c reductase did not change significantly. The decrease in the activity of the inner-membrane enzymes closely followed the disappearance of T3 and T4 from serum. 10 h after administration of 25 micrograms/100 g T3 to thyroidectomized rats, the activity of succinate and beta-hydroxybutyrate cytochrome c reductases and the oxygen consumption rate with succinate or beta-hydroxybutyrate were significantly increased, while, in the outer membrane, the activity of monoamine oxidase and rotenone-insensitive NADH-cytochrome c reductase remained unchanged. In the thyroidectomized rat, L-[3H]leucine incorporation in vivo is diminished in all the liver mitochondrial proteins, and especially in two constituents of MW 19 000 and 28 000. The radioactivity of these two components is also decreased in the normal rat treated with chloramphenicol, a specific inhibitor of mitochondrial protein synthesis. L-[14C]leucine incorporation in isolated liver mitochondria was significantly increased in the thyroidectomized rat, 10 h after T3 treatment. Thus, thyroid hormones have an early and preferential action on the mitochondrial protein synthesizing system and on the inner-membrane enzyme activities."}
{"id": "PMID:226439", "title": "Evidence for glucocorticoid transport into AtT-20 cells. Selective effect of a sulfhydryl inhibitor on uptake.", "content": "The purpose of these experiments was to determine if membrane-mediated glucocorticoid uptake by the AtT-20 cell was sensitive to the sulfhydryl group inhibitor, p-chloromercuriphenylsulfonate (PCMPS). This agent was chosen because of its reported limited entry into the cell interior. Our experimentes showed that cells could be incubated with 1 mM PCMPS for 1 h before intracellular concentrations of the inhibitor were sufficient to affect the intracellular cytosol receptor. In contrast less than 15 min of treatment inhibited intact cell steroid uptake. The inhibition was completely reversed by dithiothreitol. These studies show inhibition of glucocorticoid uptake under conditions which do not affect the intracellular receptor and infer that the AtT-20 cell membrane-mediated uptake mechanism for glucocorticoids contains sensitive sulfhydryl groups.", "contents": "Evidence for glucocorticoid transport into AtT-20 cells. Selective effect of a sulfhydryl inhibitor on uptake. The purpose of these experiments was to determine if membrane-mediated glucocorticoid uptake by the AtT-20 cell was sensitive to the sulfhydryl group inhibitor, p-chloromercuriphenylsulfonate (PCMPS). This agent was chosen because of its reported limited entry into the cell interior. Our experimentes showed that cells could be incubated with 1 mM PCMPS for 1 h before intracellular concentrations of the inhibitor were sufficient to affect the intracellular cytosol receptor. In contrast less than 15 min of treatment inhibited intact cell steroid uptake. The inhibition was completely reversed by dithiothreitol. These studies show inhibition of glucocorticoid uptake under conditions which do not affect the intracellular receptor and infer that the AtT-20 cell membrane-mediated uptake mechanism for glucocorticoids contains sensitive sulfhydryl groups."}
{"id": "PMID:226440", "title": "Effects of cannabinoids on testosterone and protein synthesis in rat testis Leydig cells in vitro.", "content": "Various water-insoluble cannabinoids as well as SP-111A, the water-soluble derivative of delta 9-tetrahydrocannabinol (delta 9-THC), reduced hCG and dibutyryl-cAMP stimulated testosterone production by rat testicular Leydig cell preparations. With 0.15 microM (0.05 micrograms/ml) 8-beta-OH-delta 9-THC the inhibition was about 50% of stimulated testosterone synthesis. Dose-related inhibitions were apparent with other cannabinoids and their order of potency in inhibiting stimulated steroidogenesis by the interstitial cells in vitro was found to be: 8-beta-OH-delta 9-THC greater than or equal to 11-OH-delta 9-THC greater than CBN = CBD = CBG greater than or equal delta 9-THC = delta 8-THC. The non-stimulated, basal, steroidogenesis was not affected even with 15 microM cannabinoids. The incorporation of L-[U-14C]leucine into the protein of Leydig cells was markedly reduced by 15 microM cannabinoids under both basal and stimulated conditions. The inhibition of steroidogenesis as well as protein synthesis in rat testicular Leydig cell preparations by various cannabinoids cannot be correlated with their psychoactivity. The present data suggest that cannabinoids at very low concentrations may interfere directly in Leydig cells with both protein and testosterone synthesis, and thus with their function.", "contents": "Effects of cannabinoids on testosterone and protein synthesis in rat testis Leydig cells in vitro. Various water-insoluble cannabinoids as well as SP-111A, the water-soluble derivative of delta 9-tetrahydrocannabinol (delta 9-THC), reduced hCG and dibutyryl-cAMP stimulated testosterone production by rat testicular Leydig cell preparations. With 0.15 microM (0.05 micrograms/ml) 8-beta-OH-delta 9-THC the inhibition was about 50% of stimulated testosterone synthesis. Dose-related inhibitions were apparent with other cannabinoids and their order of potency in inhibiting stimulated steroidogenesis by the interstitial cells in vitro was found to be: 8-beta-OH-delta 9-THC greater than or equal to 11-OH-delta 9-THC greater than CBN = CBD = CBG greater than or equal delta 9-THC = delta 8-THC. The non-stimulated, basal, steroidogenesis was not affected even with 15 microM cannabinoids. The incorporation of L-[U-14C]leucine into the protein of Leydig cells was markedly reduced by 15 microM cannabinoids under both basal and stimulated conditions. The inhibition of steroidogenesis as well as protein synthesis in rat testicular Leydig cell preparations by various cannabinoids cannot be correlated with their psychoactivity. The present data suggest that cannabinoids at very low concentrations may interfere directly in Leydig cells with both protein and testosterone synthesis, and thus with their function."}
{"id": "PMID:226441", "title": "Substance P stimulation of amylase release by isolated parotid cells and inhibition of substance P induction of salivation by vasoactive peptides.", "content": "Substance P stimulation of salivation in rats has been studied as has its in vitro enhancement of amylase release by isolated parotid cells. The extent of the stimulation on amylase release by isolated parotid cells was dependent upon the concentration of substance P, with the minimum effective concentration being 1 nM. The substance P effect was detectable within 1 min after incubation and lasted for at least 50 min. Substance P stimulation was demonstrable at 25--37 degrees C but not at 0 degrees C. Adrenocorticotropic hormone (ACTH), thyrotropin-releasing hormone (TRH), vasopressin and neurotensin had no effect on amylase release. These results suggest that substance P may act directly on the parotid cells. Examination of the salivary-stimulating activity of fragments of substance P showed that the C-terminal octapeptide and (pyroglutamyl)hexapeptide were active, although less potent than substance P, whereas its free acid, C-terminal tetra- and tri-peptides were inactive. Vasopressin, angiotensin II and neurotensin could inhibit substance P induced salivation, whereas TRH, ACTH and somatostatin had no effect. Amylase activity per unit volume of saliva was not changed by the injection of vasopressin, angiotensin II or neurotensin. These vasoactive peptides did not affect substance P stimulation of amylase release by isolated parotid cells. The results indicate that vasopressin, angiotensin II and neurotensin inhibit the action of substance P on salivation at sites other than the parotid cells.", "contents": "Substance P stimulation of amylase release by isolated parotid cells and inhibition of substance P induction of salivation by vasoactive peptides. Substance P stimulation of salivation in rats has been studied as has its in vitro enhancement of amylase release by isolated parotid cells. The extent of the stimulation on amylase release by isolated parotid cells was dependent upon the concentration of substance P, with the minimum effective concentration being 1 nM. The substance P effect was detectable within 1 min after incubation and lasted for at least 50 min. Substance P stimulation was demonstrable at 25--37 degrees C but not at 0 degrees C. Adrenocorticotropic hormone (ACTH), thyrotropin-releasing hormone (TRH), vasopressin and neurotensin had no effect on amylase release. These results suggest that substance P may act directly on the parotid cells. Examination of the salivary-stimulating activity of fragments of substance P showed that the C-terminal octapeptide and (pyroglutamyl)hexapeptide were active, although less potent than substance P, whereas its free acid, C-terminal tetra- and tri-peptides were inactive. Vasopressin, angiotensin II and neurotensin could inhibit substance P induced salivation, whereas TRH, ACTH and somatostatin had no effect. Amylase activity per unit volume of saliva was not changed by the injection of vasopressin, angiotensin II or neurotensin. These vasoactive peptides did not affect substance P stimulation of amylase release by isolated parotid cells. The results indicate that vasopressin, angiotensin II and neurotensin inhibit the action of substance P on salivation at sites other than the parotid cells."}
{"id": "PMID:226442", "title": "Insulin inhibition of lipolysis of human adipocytes: the role of cyclic adenosine monophosphate.", "content": "To gain information on the manner in which insulin suppresses lipolysis in man, isolated adipocytes, prepared from subcutaneous adipose tissue, were incubated with insulin (100 microunits/ml) alone and in combination with isoproterenol (10(-7) M or 10(-8) M). Cyclic AMP concentration was measured at 60 min; glycerol release, used as an index of lipolysis, was determined at 45 and 75 min. Insulin consistently reduced both basal and stimulated cyclic AMP and glycerol release: the degree of suppression of each was comparable. In subsequent experiments, the ability of insulin to suppress glycerol release stimulated by isoproterenol, theophylline, and dibutyryl cyclic AMP (dbcAMP), respectively, was compared. Insulin substantially reduced the raised levels of cyclic AMP and glycerol release prompted by isoproterenol and theophylline, but it had little effect on increases caused by dbcAMP. These findings support the view that reduction in cyclic AMP is an important component in the regulation of fat mobilization by insulin.", "contents": "Insulin inhibition of lipolysis of human adipocytes: the role of cyclic adenosine monophosphate. To gain information on the manner in which insulin suppresses lipolysis in man, isolated adipocytes, prepared from subcutaneous adipose tissue, were incubated with insulin (100 microunits/ml) alone and in combination with isoproterenol (10(-7) M or 10(-8) M). Cyclic AMP concentration was measured at 60 min; glycerol release, used as an index of lipolysis, was determined at 45 and 75 min. Insulin consistently reduced both basal and stimulated cyclic AMP and glycerol release: the degree of suppression of each was comparable. In subsequent experiments, the ability of insulin to suppress glycerol release stimulated by isoproterenol, theophylline, and dibutyryl cyclic AMP (dbcAMP), respectively, was compared. Insulin substantially reduced the raised levels of cyclic AMP and glycerol release prompted by isoproterenol and theophylline, but it had little effect on increases caused by dbcAMP. These findings support the view that reduction in cyclic AMP is an important component in the regulation of fat mobilization by insulin."}
{"id": "PMID:226444", "title": "Hepatic adenoma associated with portasystemic shunting in a young woman.", "content": "The development of a hepatic adenoma is described in a young female of reproductive age who had documented portasystemic shunting and hyperestrogenemia. The intrinsic hyperestrogenemia and the increased hepatic arterial blood flow, both of which occurred as a result of the portasystemic shunting secondary to portal venous obstruction, may have been important factors in the development of her hepatic tumor. We would postulate that prolonged endogenous hyperestrogenemia, like exogenous sex steroids, may predispose to hepatic adenoma formation.", "contents": "Hepatic adenoma associated with portasystemic shunting in a young woman. The development of a hepatic adenoma is described in a young female of reproductive age who had documented portasystemic shunting and hyperestrogenemia. The intrinsic hyperestrogenemia and the increased hepatic arterial blood flow, both of which occurred as a result of the portasystemic shunting secondary to portal venous obstruction, may have been important factors in the development of her hepatic tumor. We would postulate that prolonged endogenous hyperestrogenemia, like exogenous sex steroids, may predispose to hepatic adenoma formation."}
{"id": "PMID:226459", "title": "Intestinal absorption of cholecalciferol in alcoholic liver disease and primary biliary cirrhosis.", "content": "The intestinal absorption of (3H)cholecalciferol was studied in five patients with alcoholic liver disease, six patients with primary biliary cirrhosis, and 15 healthy subjects. The rate of appearance in plasma of (3H)cholecalciferol after oral ingestion and the subsequent appearance of (3H) polar metabolites in the alcoholic subjects were similar to those in the healthy subjects. In subjects with primary biliary cirrhosis the rate of appearance in plasma of (3H)cholecalciferol was significantly reduced. The rate of appearance of labelled polar metabolites of cholecalciferol was also lower in this group, suggesting that increased removal of labelled vitamin by conversion into more polar metabolites could not account for the reduced plasma (3H)cholecalciferol response. It is suggested that intestinal absorption of cholecalciferol is usually normal in alcoholic liver disease but impaired in primary biliary cirrhosis. Hepatic 25-hydroxylation is normal in alcoholic liver disease but may be defective in primary biliary cirrhosis.", "contents": "Intestinal absorption of cholecalciferol in alcoholic liver disease and primary biliary cirrhosis. The intestinal absorption of (3H)cholecalciferol was studied in five patients with alcoholic liver disease, six patients with primary biliary cirrhosis, and 15 healthy subjects. The rate of appearance in plasma of (3H)cholecalciferol after oral ingestion and the subsequent appearance of (3H) polar metabolites in the alcoholic subjects were similar to those in the healthy subjects. In subjects with primary biliary cirrhosis the rate of appearance in plasma of (3H)cholecalciferol was significantly reduced. The rate of appearance of labelled polar metabolites of cholecalciferol was also lower in this group, suggesting that increased removal of labelled vitamin by conversion into more polar metabolites could not account for the reduced plasma (3H)cholecalciferol response. It is suggested that intestinal absorption of cholecalciferol is usually normal in alcoholic liver disease but impaired in primary biliary cirrhosis. Hepatic 25-hydroxylation is normal in alcoholic liver disease but may be defective in primary biliary cirrhosis."}
{"id": "PMID:226460", "title": "R\u00f4le of calcitonin in diarrhoea associated with medullary carcinoma of the thyroid.", "content": "Severe watery diarrhoea in a patient with medullary thryoid carcinoma and high calcitonin levels was associated with increased distal ileal flow. Plasma from the patient inhibited small intestinal fluid absorption in dogs without affecting mucosal cyclic AMP levels. When calcitonin was removed from the plasma, the effect in experimental bowel loops was abolished but could be restored on restitution of comparable hormone levels with pure calcitonin. These studies, combined with the failure to find evidence of increased prostaglandin activity in the patient, suggest that circulating calcitonin may be a major cause of the diarrhoea in medullary thyroid carcinoma.", "contents": "R\u00f4le of calcitonin in diarrhoea associated with medullary carcinoma of the thyroid. Severe watery diarrhoea in a patient with medullary thryoid carcinoma and high calcitonin levels was associated with increased distal ileal flow. Plasma from the patient inhibited small intestinal fluid absorption in dogs without affecting mucosal cyclic AMP levels. When calcitonin was removed from the plasma, the effect in experimental bowel loops was abolished but could be restored on restitution of comparable hormone levels with pure calcitonin. These studies, combined with the failure to find evidence of increased prostaglandin activity in the patient, suggest that circulating calcitonin may be a major cause of the diarrhoea in medullary thyroid carcinoma."}
{"id": "PMID:226461", "title": "Acute metabolic and circulatory effects of cigarette smoking in late pregnancy.", "content": "The acute metabolic and circulatory effects of cigarette smoking (two cigarettes of a standard brand) in the last trimester of pregnancy were studied. 12 subjects, all of whom where hospitalized because of pregnancy complications, volunteered to participate in the investigation. A statistically significant immediate increment in the maternal heart rate, systolic and diastolic blood pressure, fetal heart rate, plasma glucose and plasma cyclic AMP was noted. Plasma glycerol, plasma insulin and blood lactate did not change significantly. 30 min after smoking there was a small but significant increase in plasma nonesterified fatty acids, plasma beta-hydroxybutyrate and plasma C-peptide.", "contents": "Acute metabolic and circulatory effects of cigarette smoking in late pregnancy. The acute metabolic and circulatory effects of cigarette smoking (two cigarettes of a standard brand) in the last trimester of pregnancy were studied. 12 subjects, all of whom where hospitalized because of pregnancy complications, volunteered to participate in the investigation. A statistically significant immediate increment in the maternal heart rate, systolic and diastolic blood pressure, fetal heart rate, plasma glucose and plasma cyclic AMP was noted. Plasma glycerol, plasma insulin and blood lactate did not change significantly. 30 min after smoking there was a small but significant increase in plasma nonesterified fatty acids, plasma beta-hydroxybutyrate and plasma C-peptide."}
{"id": "PMID:226464", "title": "Paraprofessional role in a mental health continuing care program.", "content": "The authors report on a unique program in which paraprofessionals provide continuing care services to patients in a large public psychiatric hospital, both before and after discharge. Data from one hundred patients indicate that paraprofessional caseworkers effectively managed 85 percent of the patients' post-discharge problems without needing to directly involve their professional teammates.", "contents": "Paraprofessional role in a mental health continuing care program. The authors report on a unique program in which paraprofessionals provide continuing care services to patients in a large public psychiatric hospital, both before and after discharge. Data from one hundred patients indicate that paraprofessional caseworkers effectively managed 85 percent of the patients' post-discharge problems without needing to directly involve their professional teammates."}
{"id": "PMID:226465", "title": "Determination of the activity of nonspecific monophosphoesterases and nonspecific esterase in the liver of dogs in extrahepatic cholestasis treated surgically and with phenobarbital.", "content": "Histochemical researches on livers of 19 dogs were carried out. The dogs suffered from extrahepatic cholestasis which lasted for 28 days and was surgically induced. The dogs were divided into three groups, out of which two were given phenobarbital for 21 or 28 days. In all groups biliary obstruction was removed by surgical operation. It was shown that a combined surgical treatment with the application of phenobarbital has given better results than a surgical treatment alone.", "contents": "Determination of the activity of nonspecific monophosphoesterases and nonspecific esterase in the liver of dogs in extrahepatic cholestasis treated surgically and with phenobarbital. Histochemical researches on livers of 19 dogs were carried out. The dogs suffered from extrahepatic cholestasis which lasted for 28 days and was surgically induced. The dogs were divided into three groups, out of which two were given phenobarbital for 21 or 28 days. In all groups biliary obstruction was removed by surgical operation. It was shown that a combined surgical treatment with the application of phenobarbital has given better results than a surgical treatment alone."}
{"id": "PMID:226467", "title": "Liver cell injury (bodies similar to Lafora's) in alcoholics treated with disulfiram (Antabuse).", "content": "Inclusions, structurally similar to Lafora's bodies, are described in the liver cells of three chronic alcoholic patients who stopped drinking after disulfiram treatment. The inclusions were strongly positive with PAS and methenamine silver stains. Shikata stain for HBsAg was negative. On electron microscopy the inclusions are not membrane-bound and contain glycogen beta-granules, secondary lysosomes containing lamellar structures, lipid droplets and filaments; the SER was almost completely lost. In the patient least affected, the cells bearing inclusions were predominantly periportal in location, as is usual in Lafora's disease. In the two other patients the change involved the whole lobule. The possibility of an induced carbohydrate metabolic disorder, which could be due to the disulfiram, a drug that interferes with the activity of several hepatic enzymes is discussed. The presence of appearances suggestive of SER breakdown could also be interpreted as a manifestation of 'disuse atrophy' due to alcohol withdrawal.", "contents": "Liver cell injury (bodies similar to Lafora's) in alcoholics treated with disulfiram (Antabuse). Inclusions, structurally similar to Lafora's bodies, are described in the liver cells of three chronic alcoholic patients who stopped drinking after disulfiram treatment. The inclusions were strongly positive with PAS and methenamine silver stains. Shikata stain for HBsAg was negative. On electron microscopy the inclusions are not membrane-bound and contain glycogen beta-granules, secondary lysosomes containing lamellar structures, lipid droplets and filaments; the SER was almost completely lost. In the patient least affected, the cells bearing inclusions were predominantly periportal in location, as is usual in Lafora's disease. In the two other patients the change involved the whole lobule. The possibility of an induced carbohydrate metabolic disorder, which could be due to the disulfiram, a drug that interferes with the activity of several hepatic enzymes is discussed. The presence of appearances suggestive of SER breakdown could also be interpreted as a manifestation of 'disuse atrophy' due to alcohol withdrawal."}
{"id": "PMID:226468", "title": "On the genetics of the human serum paraoxonase (EC 3.1.1.2).", "content": "Incubation of the sera of 799 nonrelated persons with paraoxon led to varying degrees of inhibition of the serum cholinesterase (EC 3.1.1.8) with residual activity between 0% and 67.4% of the initial activity. This is the result of a differing paraoxonase (EC 3.1.1.2) activity. The residual activities show a trimodal distribution. The results of studies of 99 families with children show that an autosomal dominant herdity factor is most likely. Consideration of the constellations of the activity values within the families can thus yield a stochastic external criterion. This, together with the shape of the distribution of the individual values, gives good statistical estimates for the distributions and frequencies of the three groups obtained by an iteration technique. Tests of association that take account of group membership show that residual activity does not depend on the blood groups A, B, O, and Rh, or on age. A conclusive argument for our assumption of three activity groups is that the resulting group frequencies are consistent with the Hardy-Weinberg rule.", "contents": "On the genetics of the human serum paraoxonase (EC 3.1.1.2). Incubation of the sera of 799 nonrelated persons with paraoxon led to varying degrees of inhibition of the serum cholinesterase (EC 3.1.1.8) with residual activity between 0% and 67.4% of the initial activity. This is the result of a differing paraoxonase (EC 3.1.1.2) activity. The residual activities show a trimodal distribution. The results of studies of 99 families with children show that an autosomal dominant herdity factor is most likely. Consideration of the constellations of the activity values within the families can thus yield a stochastic external criterion. This, together with the shape of the distribution of the individual values, gives good statistical estimates for the distributions and frequencies of the three groups obtained by an iteration technique. Tests of association that take account of group membership show that residual activity does not depend on the blood groups A, B, O, and Rh, or on age. A conclusive argument for our assumption of three activity groups is that the resulting group frequencies are consistent with the Hardy-Weinberg rule."}
{"id": "PMID:226472", "title": "Adherent cells as targets in mitogenic T-lymphocyte stimulation: replacement of lymphocyte-bound mitogens by nonmitogenic substances.", "content": "The sequence of events in mitogenic T-lymphocyte activation was investigated by employing purified mouse peritoneal adherent cells and T-lymphocyte populations. After treatment of adherent cells with the oxidizing agents sodium periodate or neuroaminidase plus galactose oxidase and removal of the mitogens, the cells acquired the ability to stimulate purified T-lymphocytes added subsequently. For this process of T-lymphocyte activation, the additional presence of the membrane interacting substances polyethylene glycol, dextran, nonmitogenic Helix pomatia agglutinin, or inactivated sendai virus was required. Lysates of mitogen-treated peritoneal adherent cells were able to replace the adherent cells in the cultures.", "contents": "Adherent cells as targets in mitogenic T-lymphocyte stimulation: replacement of lymphocyte-bound mitogens by nonmitogenic substances. The sequence of events in mitogenic T-lymphocyte activation was investigated by employing purified mouse peritoneal adherent cells and T-lymphocyte populations. After treatment of adherent cells with the oxidizing agents sodium periodate or neuroaminidase plus galactose oxidase and removal of the mitogens, the cells acquired the ability to stimulate purified T-lymphocytes added subsequently. For this process of T-lymphocyte activation, the additional presence of the membrane interacting substances polyethylene glycol, dextran, nonmitogenic Helix pomatia agglutinin, or inactivated sendai virus was required. Lysates of mitogen-treated peritoneal adherent cells were able to replace the adherent cells in the cultures."}
{"id": "PMID:226473", "title": "Altered immune reactivity in encephalomyocarditis-M variant (EMC-M)-induced diabetes in mice.", "content": "Approximately 50% of DBA/2j male mice infected with EMC-M develop glycosuria with suppressed immune responsiveness to the mitogens PHA, Con A and PWM. The greatest degree of suppression was noted with Con A treated cultures. In vivo treatment with Levamisole, a known T cell stimulant, especially increased the response to Con A but exacerbated the diabetogenic state as reflected by increased occurrence of glycosuria. Virus infected mice, given anti-lymphocyte serum (ALS), showed marked amelioration of the diabetic syndrome. Indomethacin, a non-steroidal anti-inflammatory agent as well as a prostaglandin-synthetase inhibitor, partially reversed the in vitro splenic cell suppression of infected animals.", "contents": "Altered immune reactivity in encephalomyocarditis-M variant (EMC-M)-induced diabetes in mice. Approximately 50% of DBA/2j male mice infected with EMC-M develop glycosuria with suppressed immune responsiveness to the mitogens PHA, Con A and PWM. The greatest degree of suppression was noted with Con A treated cultures. In vivo treatment with Levamisole, a known T cell stimulant, especially increased the response to Con A but exacerbated the diabetogenic state as reflected by increased occurrence of glycosuria. Virus infected mice, given anti-lymphocyte serum (ALS), showed marked amelioration of the diabetic syndrome. Indomethacin, a non-steroidal anti-inflammatory agent as well as a prostaglandin-synthetase inhibitor, partially reversed the in vitro splenic cell suppression of infected animals."}
{"id": "PMID:226477", "title": "Effect of silica on the innate resistance of inbred mice to Salmonella typhimurium infection.", "content": "The role of macrophages in the innate immunity of (CBA/N female X DBA/2N male)F1 female mice to Salmonella typhimurium was assessed with silica, an agent which has been reported to selectively inactivate macrophages. Silica, administered intravenously to mice, markedly decreased the phagocytic capacity of splenic macrophages but had no effect on splenic responsiveness to the B-cell mitogen lipopolysaccharidide or the T-cell mitogen phytohemagglutinin, nor did it affect the frequency of surface immunoglobulin-positive cells (B cells). Silica given to mice 1 day before intraperitoneal challenge decreased the 50% lethal dose of S. typhimurium 100-fold. The incidence of survival of mice given silica up to 14 days before infection with a sublethal dose of organisms was also decreased. This susceptibility could also be demonstrated when silica was given 10 days, but not 20 days, after S. typhimurium infection. Poly-2-vinylpyridine-N-oxide, a lysosomal stabilizing agent, abrogated the silica effect. Deaths among silica-treated mice followed uncontrolled multiplication of the organism in the spleen. These results provide direct evidence that macrophages play an essential role in natural immunity to murine typhoid and demonstrate the efficacy of silica as a tool to analyze macrophage function.", "contents": "Effect of silica on the innate resistance of inbred mice to Salmonella typhimurium infection. The role of macrophages in the innate immunity of (CBA/N female X DBA/2N male)F1 female mice to Salmonella typhimurium was assessed with silica, an agent which has been reported to selectively inactivate macrophages. Silica, administered intravenously to mice, markedly decreased the phagocytic capacity of splenic macrophages but had no effect on splenic responsiveness to the B-cell mitogen lipopolysaccharidide or the T-cell mitogen phytohemagglutinin, nor did it affect the frequency of surface immunoglobulin-positive cells (B cells). Silica given to mice 1 day before intraperitoneal challenge decreased the 50% lethal dose of S. typhimurium 100-fold. The incidence of survival of mice given silica up to 14 days before infection with a sublethal dose of organisms was also decreased. This susceptibility could also be demonstrated when silica was given 10 days, but not 20 days, after S. typhimurium infection. Poly-2-vinylpyridine-N-oxide, a lysosomal stabilizing agent, abrogated the silica effect. Deaths among silica-treated mice followed uncontrolled multiplication of the organism in the spleen. These results provide direct evidence that macrophages play an essential role in natural immunity to murine typhoid and demonstrate the efficacy of silica as a tool to analyze macrophage function."}
{"id": "PMID:226478", "title": "Persistent infection of human lymphoid and myeloid cell lines with herpes simplex virus.", "content": "Herpes simplex virus (HSV) type 1 replicated and persisted in human T, B, and myeloid cell lines with different patterns of viral replication and various effects on cell growth. T cell line CEM supported the replication of HSV for over 400 days without detectable differences in cell growth as compared with uninfected cells. HSV persisted in B cell line NC37 and myeloid cell line K562 for up to 222 and 374 days, respectively, but led to a significant decrease in the number of viable cells by 7 weeks of infection. The average number of cells producing infectious virus was very low in these cell lines (range, 0.5 to 2.7+) compared with a larger proportion of cells exhibiting HSV antigens by immunofluorescence (range, 24 to 58%). In contrast, null cell line LAZ 221 failed to replicate HSV even though the viral infection led to a cessation of cell growth.", "contents": "Persistent infection of human lymphoid and myeloid cell lines with herpes simplex virus. Herpes simplex virus (HSV) type 1 replicated and persisted in human T, B, and myeloid cell lines with different patterns of viral replication and various effects on cell growth. T cell line CEM supported the replication of HSV for over 400 days without detectable differences in cell growth as compared with uninfected cells. HSV persisted in B cell line NC37 and myeloid cell line K562 for up to 222 and 374 days, respectively, but led to a significant decrease in the number of viable cells by 7 weeks of infection. The average number of cells producing infectious virus was very low in these cell lines (range, 0.5 to 2.7+) compared with a larger proportion of cells exhibiting HSV antigens by immunofluorescence (range, 24 to 58%). In contrast, null cell line LAZ 221 failed to replicate HSV even though the viral infection led to a cessation of cell growth."}
{"id": "PMID:226479", "title": "Depression of bovine monocyte chemotactic responses by bovine viral diarrhea virus.", "content": "Incubation of bovine peripheral blood monocytes with bovine viral diarrhea virus (either Singer or NY-1 strain) caused a consistent, statistically significant decrease in their random locomotion (no chemoattractant) and chemotaxis towards a chemotactic lymphokine. Chemotaxis was determined by a modification of the Boyden method. Incubation of bovine viral diarrhea virus with mononuclear cells depressed chemotaxis by a mean of 56% (P less than 0.0005). Heat-killed virus had no effect on monocyte motility. Data suggest that bovine viral diarrhea virus can rapidly suppress monocyte functions in vitro, but by unknown mechanisms, not by killing cells.", "contents": "Depression of bovine monocyte chemotactic responses by bovine viral diarrhea virus. Incubation of bovine peripheral blood monocytes with bovine viral diarrhea virus (either Singer or NY-1 strain) caused a consistent, statistically significant decrease in their random locomotion (no chemoattractant) and chemotaxis towards a chemotactic lymphokine. Chemotaxis was determined by a modification of the Boyden method. Incubation of bovine viral diarrhea virus with mononuclear cells depressed chemotaxis by a mean of 56% (P less than 0.0005). Heat-killed virus had no effect on monocyte motility. Data suggest that bovine viral diarrhea virus can rapidly suppress monocyte functions in vitro, but by unknown mechanisms, not by killing cells."}
{"id": "PMID:226480", "title": "Type C virus and immunoglobulin A production by murine myeloma MOPC-315: two independent activities.", "content": "The suspected correlation between cessation of type C virus production and halt in immunoglobulin secretion by murine myeloma cells was studied. Employing two variants of the murine myeloma MOPC-315, immunoglobulin A-producing and nonproducing cells, we demonstrated that the two myelomas release similar levels of type C viruses which share common nucleotide sequences and that the viral genomes are equally expressed within the cells. Thus, the suggested relation between these two activities does not apply for MOPC-315 cells and probably for other murine myelomas also.", "contents": "Type C virus and immunoglobulin A production by murine myeloma MOPC-315: two independent activities. The suspected correlation between cessation of type C virus production and halt in immunoglobulin secretion by murine myeloma cells was studied. Employing two variants of the murine myeloma MOPC-315, immunoglobulin A-producing and nonproducing cells, we demonstrated that the two myelomas release similar levels of type C viruses which share common nucleotide sequences and that the viral genomes are equally expressed within the cells. Thus, the suggested relation between these two activities does not apply for MOPC-315 cells and probably for other murine myelomas also."}
{"id": "PMID:226481", "title": "Isolation and development of a reticuloendotheliosis virus-transformed lymphoblastoid cell line from chicken spleen cells.", "content": "The establishment and characterization of a reticuloendotheliosis virus (strain T)-transformed lymphoblastoid cell line, designated TV-1, was reported. These cells, isolated from the spleen of a moribund chick infected with reticuloendotheliosis virus, were maintained in suspension culture for over 74 weeks at a stable generation time of 15 h. The cells were found to carry a female karyotype. Both TV-1 cells and cell-free TV-1 culture supernatant produced lesions and mortality patterns in chicks which were identical to those caused by reticuloendotheliosis virus (strain T) infection. Examination of TV-1 cells by electron microscope revealed the presence of C-type virions budding from the plasma membrane. Cytotoxicity assays and fluorescent antibody tests indicated the presence of B-cell determinants on the TV-1 cell surface membrane.", "contents": "Isolation and development of a reticuloendotheliosis virus-transformed lymphoblastoid cell line from chicken spleen cells. The establishment and characterization of a reticuloendotheliosis virus (strain T)-transformed lymphoblastoid cell line, designated TV-1, was reported. These cells, isolated from the spleen of a moribund chick infected with reticuloendotheliosis virus, were maintained in suspension culture for over 74 weeks at a stable generation time of 15 h. The cells were found to carry a female karyotype. Both TV-1 cells and cell-free TV-1 culture supernatant produced lesions and mortality patterns in chicks which were identical to those caused by reticuloendotheliosis virus (strain T) infection. Examination of TV-1 cells by electron microscope revealed the presence of C-type virions budding from the plasma membrane. Cytotoxicity assays and fluorescent antibody tests indicated the presence of B-cell determinants on the TV-1 cell surface membrane."}
{"id": "PMID:226482", "title": "Cytolytic activity of macrophages isolated from primary murine sarcoma virus (MSV)-induced tumors.", "content": "Macrophages isolated from regressing or progressing tumors induced by murine sarcoma virus (MSV) were tested for cytolytic activity in a 18-h 51Cr release assay. Macrophages from the tumors of mice injected 14 days earlier with stocks of MSV-producing regressor or progressor tumors had comparable levels of cytotoxicity. However, macrophages from the progressively growing tumors, 50--65 days after the inoculation with the progressor virus, had lower levels of cytotoxicity than those from the regressing tumors (day 14). On the other hand, macrophages from progressively growing MSV tumors (day 14) in nude mice had little or no detectable cytolytic activity. In a fractionation study, using the 1-g velocity sedimentation technique, cells from regressing tumors (day 14) showed at least two peaks of cytolytic activity, one at about 4 mm/h and another at 6--7 mm/h. In contrast, none of the cell fractions of tumors from nude mice (day 14) showed cytolytic activity. Since bacterial lipopolysaccharide (LPS) has been shown to augment the cytolytic activity of primed macrophages, its effect on cells from MSV tumors was evaluated. Cytolytic activity of the cells from regressing or progr-ssing tumors that had pre-existing cytolytic activity was augmented by the addition of LPS during the assay period, but LPS treatment did not activate inactive fractions or change the distribution patterns of the cytolytic activity in fractions from 1-g velocity sedimentation.", "contents": "Cytolytic activity of macrophages isolated from primary murine sarcoma virus (MSV)-induced tumors. Macrophages isolated from regressing or progressing tumors induced by murine sarcoma virus (MSV) were tested for cytolytic activity in a 18-h 51Cr release assay. Macrophages from the tumors of mice injected 14 days earlier with stocks of MSV-producing regressor or progressor tumors had comparable levels of cytotoxicity. However, macrophages from the progressively growing tumors, 50--65 days after the inoculation with the progressor virus, had lower levels of cytotoxicity than those from the regressing tumors (day 14). On the other hand, macrophages from progressively growing MSV tumors (day 14) in nude mice had little or no detectable cytolytic activity. In a fractionation study, using the 1-g velocity sedimentation technique, cells from regressing tumors (day 14) showed at least two peaks of cytolytic activity, one at about 4 mm/h and another at 6--7 mm/h. In contrast, none of the cell fractions of tumors from nude mice (day 14) showed cytolytic activity. Since bacterial lipopolysaccharide (LPS) has been shown to augment the cytolytic activity of primed macrophages, its effect on cells from MSV tumors was evaluated. Cytolytic activity of the cells from regressing or progr-ssing tumors that had pre-existing cytolytic activity was augmented by the addition of LPS during the assay period, but LPS treatment did not activate inactive fractions or change the distribution patterns of the cytolytic activity in fractions from 1-g velocity sedimentation."}
{"id": "PMID:226483", "title": "Role of interferon in the pathogenesis of virus diseases in mice as demonstrated by the use of anti-interferon serum. VI. Polyoma virus infection.", "content": "We have determined the effect of a single injection of potent sheep anti-mouse interferon globulin on polyoma-virus-induced early runting disease and tumor formation in Swiss mice. When newborn mice were injected with greater than or equal to 9 X 10(6) PFU of polyoma virus, 16% (7/44) of mice runted and died in contrast to 96% (45/47) of mice injected with virus and anti-interferon globulin. Likewise, a greater percentage of mice injected with lower doses of virus and anti-interferon globulin developed tumors than did control virus-injected mice. These results suggest that interferon is an important factor in determining the susceptibility of newborn mice to polyoma virus.", "contents": "Role of interferon in the pathogenesis of virus diseases in mice as demonstrated by the use of anti-interferon serum. VI. Polyoma virus infection. We have determined the effect of a single injection of potent sheep anti-mouse interferon globulin on polyoma-virus-induced early runting disease and tumor formation in Swiss mice. When newborn mice were injected with greater than or equal to 9 X 10(6) PFU of polyoma virus, 16% (7/44) of mice runted and died in contrast to 96% (45/47) of mice injected with virus and anti-interferon globulin. Likewise, a greater percentage of mice injected with lower doses of virus and anti-interferon globulin developed tumors than did control virus-injected mice. These results suggest that interferon is an important factor in determining the susceptibility of newborn mice to polyoma virus."}
{"id": "PMID:226484", "title": "Biological and biochemical observations on isolates of EB virus from the malignant epithelial cells of two nasopharyngeal carcinomas.", "content": "Foetal, adult seronegative, and cotton-top marmoset lymphocytes have been transformed into cell lines by EB virus from the malignant epithelial cells of two nasopharyngeal carcinomas. The nature of the cell lines was checked by karyotyping and by light and electron microscopy, and the presence of the EB virus genome was demonstrated by immunofluorescence tests. Immunofluorescence also showed the incidence of EB virus-producing cells in each line and this was checked by electron microscopy and the use of a lymphocyte transformation assay. Two foetal-derived lines did not produce virus spontaneously, could not be activated with various inducers, and were found by DNA reassociation kinetics to carry only small numbers of genome copies per cell. An adult-derived line produced virus, could be activated to produce more, and provided enough infectivity to transform marmoset cells. The resulting marmoset line made profuse transforming virus; it thus provides the first abundant source of NPC-derived infectious EB virus for comparative studies. The results are discussed in relation to the interactions with comparable target cells of EB virus from normal individuals and from patients with other diseases.", "contents": "Biological and biochemical observations on isolates of EB virus from the malignant epithelial cells of two nasopharyngeal carcinomas. Foetal, adult seronegative, and cotton-top marmoset lymphocytes have been transformed into cell lines by EB virus from the malignant epithelial cells of two nasopharyngeal carcinomas. The nature of the cell lines was checked by karyotyping and by light and electron microscopy, and the presence of the EB virus genome was demonstrated by immunofluorescence tests. Immunofluorescence also showed the incidence of EB virus-producing cells in each line and this was checked by electron microscopy and the use of a lymphocyte transformation assay. Two foetal-derived lines did not produce virus spontaneously, could not be activated with various inducers, and were found by DNA reassociation kinetics to carry only small numbers of genome copies per cell. An adult-derived line produced virus, could be activated to produce more, and provided enough infectivity to transform marmoset cells. The resulting marmoset line made profuse transforming virus; it thus provides the first abundant source of NPC-derived infectious EB virus for comparative studies. The results are discussed in relation to the interactions with comparable target cells of EB virus from normal individuals and from patients with other diseases."}
{"id": "PMID:226485", "title": "Effect of sodium butyrate on the antiviral and anticellular action of interferon in normal and MSV-transformed cells.", "content": "Sodium butyrate enhances the antiviral and anticellular action of interferon in MSV-transformed cells but has no such effect in normal cells. The increased sensitivity could be mediated at least partially by the butyrate-induced elaboration of the microtubule and microfilament network.", "contents": "Effect of sodium butyrate on the antiviral and anticellular action of interferon in normal and MSV-transformed cells. Sodium butyrate enhances the antiviral and anticellular action of interferon in MSV-transformed cells but has no such effect in normal cells. The increased sensitivity could be mediated at least partially by the butyrate-induced elaboration of the microtubule and microfilament network."}
{"id": "PMID:226486", "title": "Tritiated thymidine as a broad spectrum initiator in transplacental two-stage carcinogenesis, with phorbol as promoter.", "content": "A single subcutaneous injection of 200 mu Ci [3H] thymidine into pregnant BALD/c mice, followed by intraperitoneal injections of phorbol, twice weekly for 25 weeks, in the offspring, resulted in higher tumour development in the lungs and livers of male and, to a lesser extent, of female offspring, than in their untreated littermates. The difference in overall tumour incidence was statistically significant, but the increases of the individual tumour types were only of borderline significance. Slight carcinogenic activity of [3H]thymidine alone was observed in the mothers, and in the offspring, without phorbol treatment. The results suggest the possibility of using [3H]thymidine as a broad spectrum initiator for transplacental two-stage carcinogenicity studies to determine the organ specificity of different promoting agents.", "contents": "Tritiated thymidine as a broad spectrum initiator in transplacental two-stage carcinogenesis, with phorbol as promoter. A single subcutaneous injection of 200 mu Ci [3H] thymidine into pregnant BALD/c mice, followed by intraperitoneal injections of phorbol, twice weekly for 25 weeks, in the offspring, resulted in higher tumour development in the lungs and livers of male and, to a lesser extent, of female offspring, than in their untreated littermates. The difference in overall tumour incidence was statistically significant, but the increases of the individual tumour types were only of borderline significance. Slight carcinogenic activity of [3H]thymidine alone was observed in the mothers, and in the offspring, without phorbol treatment. The results suggest the possibility of using [3H]thymidine as a broad spectrum initiator for transplacental two-stage carcinogenicity studies to determine the organ specificity of different promoting agents."}
{"id": "PMID:226488", "title": "Absence of ecotropic or recombinant murine leukaemia virus in preleukaemic and leukaemic X-irradiated NZB mice.", "content": "NZB mice X-irradiated with a single dose of 630 R when they were 1-month old developed a high incidence of histologically defined lymphocytic leukaemia 8--25 weeks later. We have screened for murine leukaemia viruses (MuLV) in the lymphoid tissues of 8 of these leukaemic mice, and in 8 \"preleukaemic\", apparently healthy NZBs killed 1 month post irradiation. Xenotropic, but not ecotropic or recombinant MuLV, was detected by in vitro co-cultivation of bone marrow, spleen and thymus with selectively permissive cell lines, followed by the immunofluorescence test for MuLV gs antigen, and the XC test. Our results are not consistent, therefore, with the concept that the factor causing the leukaemias was an oncogenic virus activated by X-irradiation.", "contents": "Absence of ecotropic or recombinant murine leukaemia virus in preleukaemic and leukaemic X-irradiated NZB mice. NZB mice X-irradiated with a single dose of 630 R when they were 1-month old developed a high incidence of histologically defined lymphocytic leukaemia 8--25 weeks later. We have screened for murine leukaemia viruses (MuLV) in the lymphoid tissues of 8 of these leukaemic mice, and in 8 \"preleukaemic\", apparently healthy NZBs killed 1 month post irradiation. Xenotropic, but not ecotropic or recombinant MuLV, was detected by in vitro co-cultivation of bone marrow, spleen and thymus with selectively permissive cell lines, followed by the immunofluorescence test for MuLV gs antigen, and the XC test. Our results are not consistent, therefore, with the concept that the factor causing the leukaemias was an oncogenic virus activated by X-irradiation."}
{"id": "PMID:226490", "title": "The epidemiology of Entamoeba histolytica in a Nigerian urban population.", "content": "Microscopic examination of multiple faeces samples of 2 825 persons was carried out in the Metropolitan Lagos. Overall prevalence of Entamoeba histolytica was 11.2%. Prevalence increased rapidly in younger age groups and there were no real differences between males and females. Prevalence was high among families who ate together from the same plate, among those who ate with their fingers and among those who ate away from home. Prevalence was not associated with type of water supply but was seemingly influenced by storage of household supplies. A low infection rate was associated with the availability of water closets and toilet habit. No association was found between prevalence and standard of education but the rate of infection was increased among workers with high occupational interaction. Significant differences were found among different ethnic groups. The highest infection rate was recorded in the last month of the wet season.", "contents": "The epidemiology of Entamoeba histolytica in a Nigerian urban population. Microscopic examination of multiple faeces samples of 2 825 persons was carried out in the Metropolitan Lagos. Overall prevalence of Entamoeba histolytica was 11.2%. Prevalence increased rapidly in younger age groups and there were no real differences between males and females. Prevalence was high among families who ate together from the same plate, among those who ate with their fingers and among those who ate away from home. Prevalence was not associated with type of water supply but was seemingly influenced by storage of household supplies. A low infection rate was associated with the availability of water closets and toilet habit. No association was found between prevalence and standard of education but the rate of infection was increased among workers with high occupational interaction. Significant differences were found among different ethnic groups. The highest infection rate was recorded in the last month of the wet season."}
{"id": "PMID:226491", "title": "Secondary structure prediction of anterior pituitary hormones. Lack of correlation between predicted values and circular dichroism data.", "content": "The secondary structures of human somatotropin, human choriomammotropin, ovine and porcine prolactin, human, ovine and porcine beta-lipotropin, human and ovine lutropin, human thyrotropin, human corticotropin, alpha-melanotropin and human beta-melanotropin have been predicted by the method of Chou & Fasman. Predicted contents of alpha-helix and beta-sheet do not correspond well with values estimated from circular dichroism spectra.", "contents": "Secondary structure prediction of anterior pituitary hormones. Lack of correlation between predicted values and circular dichroism data. The secondary structures of human somatotropin, human choriomammotropin, ovine and porcine prolactin, human, ovine and porcine beta-lipotropin, human and ovine lutropin, human thyrotropin, human corticotropin, alpha-melanotropin and human beta-melanotropin have been predicted by the method of Chou & Fasman. Predicted contents of alpha-helix and beta-sheet do not correspond well with values estimated from circular dichroism spectra."}
{"id": "PMID:226492", "title": "Further characterization of the ovine lutropin alpha and beta subunits prepared by the salt precipitation method.", "content": "The subunits of ovine lutropin prepared by acid dissociation and salt precipitation were characterized by end group analysis, tryptic peptide mapping, SDS gel electrophoresis and biological activity. No evidence of internal peptide cleavage was found in the alpha subunit. The subunits possessed low activity. The alpha and beta subunits recombined effectively to generate a complex that had full receptor binding activity and in vitro biological activity. The recombinants of subunits prepared by countercurrent distribution showed only 50% activity in both assays. The salt precipitation method alpha subunit could be completely reduced and reoxidized in the absence of denaturants. The reoxidized alpha subunit combines with the native beta subunit generating full activity. However, this recombined hormone tends to lose activity with time, suggesting that the reoxidation may not fully restore the native structur of the reduced alpha subunit. The native lutropin alpha subunit effectively combined with follitropin beta subunit generating complete follitropin activity.", "contents": "Further characterization of the ovine lutropin alpha and beta subunits prepared by the salt precipitation method. The subunits of ovine lutropin prepared by acid dissociation and salt precipitation were characterized by end group analysis, tryptic peptide mapping, SDS gel electrophoresis and biological activity. No evidence of internal peptide cleavage was found in the alpha subunit. The subunits possessed low activity. The alpha and beta subunits recombined effectively to generate a complex that had full receptor binding activity and in vitro biological activity. The recombinants of subunits prepared by countercurrent distribution showed only 50% activity in both assays. The salt precipitation method alpha subunit could be completely reduced and reoxidized in the absence of denaturants. The reoxidized alpha subunit combines with the native beta subunit generating full activity. However, this recombined hormone tends to lose activity with time, suggesting that the reoxidation may not fully restore the native structur of the reduced alpha subunit. The native lutropin alpha subunit effectively combined with follitropin beta subunit generating complete follitropin activity."}
{"id": "PMID:226493", "title": "Relationship of geniculate and occipital PGO waves and the effects of nonvisual sensory activity.", "content": "The nature of occipital PGO waves (REM) was addressed by comparing the occipital PGO waves measured at the marginal gyrus with the geniculate PGO waves and the occipital PGO waves \"directly\" transmitted to the occipital cortex. The directly transmitted PGO waves lack the first short positive-going spike that precedes the negative phase of the occipital PGO waves. The \"directly\" transmitted PGO wave was recorded from cats with either deafferented or excised LG nucleus. The \"directly\" transmitted PGO wave resembled pontine negative-going PGO wave more regarding amplitude and wave shape changes than the occipital PGO waves of intact cats. The ascending negativity of pontine PGO waves is indirectly transmitted through phasic increase of the local excitatory processes, more in the LG than in the occipital cortex. The PGO waves seem to be affected by endogenous and exogenous nonvisual processes, more in the LG than the occipital cells alone. The occipital PGO waves seem to result from the vectorial sum of geniculate and \"directly\" transmitted occipital PGO waves.", "contents": "Relationship of geniculate and occipital PGO waves and the effects of nonvisual sensory activity. The nature of occipital PGO waves (REM) was addressed by comparing the occipital PGO waves measured at the marginal gyrus with the geniculate PGO waves and the occipital PGO waves \"directly\" transmitted to the occipital cortex. The directly transmitted PGO waves lack the first short positive-going spike that precedes the negative phase of the occipital PGO waves. The \"directly\" transmitted PGO wave was recorded from cats with either deafferented or excised LG nucleus. The \"directly\" transmitted PGO wave resembled pontine negative-going PGO wave more regarding amplitude and wave shape changes than the occipital PGO waves of intact cats. The ascending negativity of pontine PGO waves is indirectly transmitted through phasic increase of the local excitatory processes, more in the LG than in the occipital cortex. The PGO waves seem to be affected by endogenous and exogenous nonvisual processes, more in the LG than the occipital cells alone. The occipital PGO waves seem to result from the vectorial sum of geniculate and \"directly\" transmitted occipital PGO waves."}
{"id": "PMID:226497", "title": "Reversible binding of vibrio cholerae toxin on NAD-sepharose.", "content": "When a crude or partially purified culture of Vibrio Cholerae is passed through a column of NAD-Sepharose, the skin toxic material is bound to the gel. Choleragen may be recovered by increasing the ionic strength of the elution buffer, as shown by the skin test, immunodiffusion against anti-choleragen antiserum and polyacrylamide gel electrophoresis. Affinity chromatography on NAD-Sepharose may be helpful for the concentration and purification of Choleragen.", "contents": "Reversible binding of vibrio cholerae toxin on NAD-sepharose. When a crude or partially purified culture of Vibrio Cholerae is passed through a column of NAD-Sepharose, the skin toxic material is bound to the gel. Choleragen may be recovered by increasing the ionic strength of the elution buffer, as shown by the skin test, immunodiffusion against anti-choleragen antiserum and polyacrylamide gel electrophoresis. Affinity chromatography on NAD-Sepharose may be helpful for the concentration and purification of Choleragen."}
{"id": "PMID:226504", "title": "[Organ preserving surgical treatment of solitary and bilateral renal tumors].", "content": "The surgical treatment of patients with tumours in solitary kidneys and bilateral renal tumours is controversial. Conservative surgical procedures by excision of the tumour in situ or by extracorporeal \"work bench surgery\" with subsequent autotransplantation are a real alternative to radical nephrectomy which necessitates chronic dialysis or renal allotransplantation. 23 patients with tumours in solitary kidneys resp. bilateral renal tumours have been treated by local excision in situ (10 patients) or extracorporeal surgery (15 patients). The preoperative diagnostic investigations, indications for in situ resp. extracorporeal surgery, details of the operative procedure and results of treatment are presented and discussed.", "contents": "[Organ preserving surgical treatment of solitary and bilateral renal tumors]. The surgical treatment of patients with tumours in solitary kidneys and bilateral renal tumours is controversial. Conservative surgical procedures by excision of the tumour in situ or by extracorporeal \"work bench surgery\" with subsequent autotransplantation are a real alternative to radical nephrectomy which necessitates chronic dialysis or renal allotransplantation. 23 patients with tumours in solitary kidneys resp. bilateral renal tumours have been treated by local excision in situ (10 patients) or extracorporeal surgery (15 patients). The preoperative diagnostic investigations, indications for in situ resp. extracorporeal surgery, details of the operative procedure and results of treatment are presented and discussed."}
{"id": "PMID:226505", "title": "[Acute emphysematous cholecystitis].", "content": "Emphysematous cholecystitis is a rare form of acute cholecystitis, characterized radiographically by the presence of gas within the gallbladder. We report of a patient, who was admitted to the hospital with the diagnosis of acute abdomen. This patient had an emphysematous cholecystitis caused by Clostridium perfringens. We found the wall of the gallbladder emphysematous and gangrenous, the gallbladder was distended and contained purulent material, but no stones. However, in addition, the films of abdomen showed gas in the ducts. Diagnosis, pathogenesis and the aetiological and therapeutical aspects will be discussed.", "contents": "[Acute emphysematous cholecystitis]. Emphysematous cholecystitis is a rare form of acute cholecystitis, characterized radiographically by the presence of gas within the gallbladder. We report of a patient, who was admitted to the hospital with the diagnosis of acute abdomen. This patient had an emphysematous cholecystitis caused by Clostridium perfringens. We found the wall of the gallbladder emphysematous and gangrenous, the gallbladder was distended and contained purulent material, but no stones. However, in addition, the films of abdomen showed gas in the ducts. Diagnosis, pathogenesis and the aetiological and therapeutical aspects will be discussed."}
{"id": "PMID:226508", "title": "Electron microscopic studies on the endometrium of the grey seal (Halichoerus grypus) during its preparation for nidation.", "content": "The uterine luminal and glandular epithelia of two mature grey seals, a species with obligate delayed implantation, have been examined. Earlier studies of their corpora lutea had suggested that these females were in the pre-nidatory condition. Ultrastructural features of these epithelia in the animal which possessed the more mature corpus luteum indicated that the luminal epithelium had attained a state of differentiation similar to that of the pre-attachment phase in the laboratory rat, a state known to be compatible with nidation. The animal with the less well developed corpus luteum demonstrated the early stages of the early endometrial response to progesterone (the hormone which takes the uterus out of the delay condition). In the grey seal, despite the late start, a similar sequence of morphological changes to those present in the endometrium of normally implanting animals occurs. Thus, it seems that in the majority of eutherian mammals, endometrial preparation for nidation follows a relatively standard pattern, and occurs pari passu with the differentiation of the luteal tissue.", "contents": "Electron microscopic studies on the endometrium of the grey seal (Halichoerus grypus) during its preparation for nidation. The uterine luminal and glandular epithelia of two mature grey seals, a species with obligate delayed implantation, have been examined. Earlier studies of their corpora lutea had suggested that these females were in the pre-nidatory condition. Ultrastructural features of these epithelia in the animal which possessed the more mature corpus luteum indicated that the luminal epithelium had attained a state of differentiation similar to that of the pre-attachment phase in the laboratory rat, a state known to be compatible with nidation. The animal with the less well developed corpus luteum demonstrated the early stages of the early endometrial response to progesterone (the hormone which takes the uterus out of the delay condition). In the grey seal, despite the late start, a similar sequence of morphological changes to those present in the endometrium of normally implanting animals occurs. Thus, it seems that in the majority of eutherian mammals, endometrial preparation for nidation follows a relatively standard pattern, and occurs pari passu with the differentiation of the luteal tissue."}
{"id": "PMID:226509", "title": "A reappraisal of the effects of ACTH on the response of the central nervous system to injury.", "content": "ACTH possesses powerful immuno-suppressive properties and also retards healing by inhibiting fibroblast proliferation and the deposition of collagen. In the present work this hormone was used to test both the 'barrier' and 'immune' hypotheses relating to the failure of CNS regeneration after injury, dosages being administered which had been found to stimulate maximal adrenal production of glucocorticoids in control animals. Although the scarring in the CNS and the systemic humoral and cellular immune responses were significantly depressed, no increase in CNS axon growth was noted, even when large doses of thyroxine were added. We conclude that both 'immune' and 'barrier' hypotheses should be rejected, and that the beneficial effects of thyroxine treatment reported by some workers are not substantiated.", "contents": "A reappraisal of the effects of ACTH on the response of the central nervous system to injury. ACTH possesses powerful immuno-suppressive properties and also retards healing by inhibiting fibroblast proliferation and the deposition of collagen. In the present work this hormone was used to test both the 'barrier' and 'immune' hypotheses relating to the failure of CNS regeneration after injury, dosages being administered which had been found to stimulate maximal adrenal production of glucocorticoids in control animals. Although the scarring in the CNS and the systemic humoral and cellular immune responses were significantly depressed, no increase in CNS axon growth was noted, even when large doses of thyroxine were added. We conclude that both 'immune' and 'barrier' hypotheses should be rejected, and that the beneficial effects of thyroxine treatment reported by some workers are not substantiated."}
{"id": "PMID:226514", "title": "Adenosine-5'-O-(3-thiotriphosphate) as an affinity probe for studying leader RNA's transcribed by vesicular stomatitis virus.", "content": "The ATP required for in vitro transcription by vesicular stomatitis virus can be replaced by the analogue adenosine-5'-O-(3-thiotriphosphate) without affecting the rate of transcription or the nature of the mRNA products. RNA chains (less than 5 S) initiated with adenosine-5'-O-(3-thiotriphosphate) can be isolated by affinity chromatography on mercury-agarose columns used in these experiments. At least 80% of the leader RNA synthesized in vitro by infectious B virions and 70% of the leader RNA synthesized by defective-interfering particles of vesicular stomatitis virus contained a 5'-terminal triphosphate as judged by binding to mercury-agarose of leader RNA synthesized in the presence of the 5'-thiotriphosphate adenosine analogue.", "contents": "Adenosine-5'-O-(3-thiotriphosphate) as an affinity probe for studying leader RNA's transcribed by vesicular stomatitis virus. The ATP required for in vitro transcription by vesicular stomatitis virus can be replaced by the analogue adenosine-5'-O-(3-thiotriphosphate) without affecting the rate of transcription or the nature of the mRNA products. RNA chains (less than 5 S) initiated with adenosine-5'-O-(3-thiotriphosphate) can be isolated by affinity chromatography on mercury-agarose columns used in these experiments. At least 80% of the leader RNA synthesized in vitro by infectious B virions and 70% of the leader RNA synthesized by defective-interfering particles of vesicular stomatitis virus contained a 5'-terminal triphosphate as judged by binding to mercury-agarose of leader RNA synthesized in the presence of the 5'-thiotriphosphate adenosine analogue."}
{"id": "PMID:226515", "title": "Preparation of biologically active radioiodinated cholecystokinin for radioreceptor assay and radioimmunoassay.", "content": "A modified method is described for the preparation of stable, high specific activity radioiodinated cholecystokinin (CCK) by its conjugation to 125I-Bolton Hunter reagent (125I-BH). Purified radioiodinated CCK (125I-BH-CCK) stimulated amylase release from isolate rat pancreatic acini with a potency identical to that of native CCK. Further, 125I-BH-CCK was highly immunoreactive and reacted with antisera directed toward both the NH2- and COOH-terminal portions of the CCK molecule. Finally, 125I-BH-CCK bound to specific receptor sites on isolated pancreatic acini.", "contents": "Preparation of biologically active radioiodinated cholecystokinin for radioreceptor assay and radioimmunoassay. A modified method is described for the preparation of stable, high specific activity radioiodinated cholecystokinin (CCK) by its conjugation to 125I-Bolton Hunter reagent (125I-BH). Purified radioiodinated CCK (125I-BH-CCK) stimulated amylase release from isolate rat pancreatic acini with a potency identical to that of native CCK. Further, 125I-BH-CCK was highly immunoreactive and reacted with antisera directed toward both the NH2- and COOH-terminal portions of the CCK molecule. Finally, 125I-BH-CCK bound to specific receptor sites on isolated pancreatic acini."}
{"id": "PMID:226516", "title": "Mitochondria contain a distinct DNA topoisomerase.", "content": "A topoisomerase (nicking-closing enzyme) has been isolated from rat liver mitochondria. It has purified by double-stranded DNA-cellulose chromatography approximately 50,000-fold, based on the crude mitochondrial extract. It possesses a minimum specific activity of 1.9 x 10(5) units/mg. The enzyme has been shown to be distinctly mitochondrial, differentiated from the nuclear topoisomerase by its sensitivity to the intercalating drug, ethidium bromide, and to the non-intercalating trypanocidal drug, Berenil.", "contents": "Mitochondria contain a distinct DNA topoisomerase. A topoisomerase (nicking-closing enzyme) has been isolated from rat liver mitochondria. It has purified by double-stranded DNA-cellulose chromatography approximately 50,000-fold, based on the crude mitochondrial extract. It possesses a minimum specific activity of 1.9 x 10(5) units/mg. The enzyme has been shown to be distinctly mitochondrial, differentiated from the nuclear topoisomerase by its sensitivity to the intercalating drug, ethidium bromide, and to the non-intercalating trypanocidal drug, Berenil."}
{"id": "PMID:226517", "title": "Coordinated modulation of albumin synthesis and mRNA levels in cultured hepatoma cells by hydrocortisone and cyclic AMP analogs.", "content": "The treatment of Hepa-2 cells, a permanent mouse hepatoma cell line, for 72 h with hydrocortisone (10(-6) M), N6,O2-dibutyryl cyclic AMP (10(-3) M), or 8-bromocyclic AMP (10(-3) M) results in a 2-,3- or 4-fold increase, respectively, in rates of synthesis and secretion of mouse serum albumin. Simultaneous treatment with hydrocortisone and N6,O2-dibutyryl cyclic AMP results in a 10-fold stimulation in these parameters, an effect that is significantly more than additive for the two compounds tested. The number of albumin mRNA sequences, determined by hybridization of total cell RNA to albumin complementary DNA, was increased in direct proportion to the increases in albumin synthesis in all experiments. The relative rate of albumin synthesis approaches in vivo levels in cells treated simultaneously with hydrocortisone and N6,O2-dibutyryl cyclic AMP. We propose that these factors may be necessary to maintain the maximal level of differentiated function in the continuous culture of Hepa-2 cells.", "contents": "Coordinated modulation of albumin synthesis and mRNA levels in cultured hepatoma cells by hydrocortisone and cyclic AMP analogs. The treatment of Hepa-2 cells, a permanent mouse hepatoma cell line, for 72 h with hydrocortisone (10(-6) M), N6,O2-dibutyryl cyclic AMP (10(-3) M), or 8-bromocyclic AMP (10(-3) M) results in a 2-,3- or 4-fold increase, respectively, in rates of synthesis and secretion of mouse serum albumin. Simultaneous treatment with hydrocortisone and N6,O2-dibutyryl cyclic AMP results in a 10-fold stimulation in these parameters, an effect that is significantly more than additive for the two compounds tested. The number of albumin mRNA sequences, determined by hybridization of total cell RNA to albumin complementary DNA, was increased in direct proportion to the increases in albumin synthesis in all experiments. The relative rate of albumin synthesis approaches in vivo levels in cells treated simultaneously with hydrocortisone and N6,O2-dibutyryl cyclic AMP. We propose that these factors may be necessary to maintain the maximal level of differentiated function in the continuous culture of Hepa-2 cells."}
{"id": "PMID:226518", "title": "Nucleotide release from tubulin and nucleoside-5'-diphosphate kinase action in microtubule assembly.", "content": "ATP and UTP support microtubule assembly through the action of brain nucleoside-5'-diphosphate kinase on GDP. Penningroth and Kirschner (1977) J. Mol. Biol. 115, 643-673) have proposed that microtubule assembly may occur by either of two mechanisms: indirectly, through nucleoside-5'-diphosphate kinase-catalyzed phosphorylation of uncomplexed GDP and directly by nucleoside-5'-diphosphate kinase-mediated transphosphorylation of tubulin-bound GDP at low tubulin concentrations. We find the rates of GDP and GTP release (0.68 and 0.32 min-1, respectively) are sufficiently fast relative to assembly to permit GDP release, phosphorylation, and GTP binding as the sole mechanism of nucleoside-5'-diphosphate kinase action in microtubule assembly. Computer simulation studies accord with the conclusion that GDP release is rapid relative to microtubule assembly. The specific activity of the nucleoside-5'-diphosphate kinase is 1.7 nmol/min/mg of microtubular protein under the conditions studied. Pulse-chase experiments with tubulin . [14C]GDP complex and the rapidity of GDP phosphorylation by the kinase are in agreement with this scheme. Finally, it was observed that the extent and rate of microtubule assembly depends upon the [ATP]/[ADP] ratio.", "contents": "Nucleotide release from tubulin and nucleoside-5'-diphosphate kinase action in microtubule assembly. ATP and UTP support microtubule assembly through the action of brain nucleoside-5'-diphosphate kinase on GDP. Penningroth and Kirschner (1977) J. Mol. Biol. 115, 643-673) have proposed that microtubule assembly may occur by either of two mechanisms: indirectly, through nucleoside-5'-diphosphate kinase-catalyzed phosphorylation of uncomplexed GDP and directly by nucleoside-5'-diphosphate kinase-mediated transphosphorylation of tubulin-bound GDP at low tubulin concentrations. We find the rates of GDP and GTP release (0.68 and 0.32 min-1, respectively) are sufficiently fast relative to assembly to permit GDP release, phosphorylation, and GTP binding as the sole mechanism of nucleoside-5'-diphosphate kinase action in microtubule assembly. Computer simulation studies accord with the conclusion that GDP release is rapid relative to microtubule assembly. The specific activity of the nucleoside-5'-diphosphate kinase is 1.7 nmol/min/mg of microtubular protein under the conditions studied. Pulse-chase experiments with tubulin . [14C]GDP complex and the rapidity of GDP phosphorylation by the kinase are in agreement with this scheme. Finally, it was observed that the extent and rate of microtubule assembly depends upon the [ATP]/[ADP] ratio."}
{"id": "PMID:226520", "title": "Flavokinase and FAD synthetase from Bacillus subtilis specific for reduced flavins.", "content": "A flavokinase preparation from Bacillus subtilis is described which catalyzes the phosphorylation of reduced, but not oxidized, riboflavin. The enzyme is distinguished from other known flavokinases also in having an unusually low Km for the flavin substrate, 50 to 100 nM. ATP is the obligatory phosphate donor; one ATP is utilized for each FMNH2 formed. Mg2+ or Zn2+ is required for the reaction; Co2+ and Mn2+ will substitute, but less effectively. The same enzyme preparation catalyzes the synthesis of FADH2 from FMNH2 and ATP, but not the synthesis of FAD from FMN and ATP. FADH2 is also formed from reduced riboflavin, presumably by sequential flavokinase and FAD synthetase action. Zn2+ cannot replace Mg2+ in FADH2 formation. The reverse reaction, formation of FMN from FAD, occurs only with reduced FAD, giving rise to FMNH2, and is dependent on the presence of inorganic pyrophosphate. The enzyme thus appears to be an FADH2 pyrophosphorylase. The two enzymatic activities, flavokinase and FADH2 pyrophosphorylase, although not separated during the purification procedure, are distinguished by differences in metal ion specificity, in concentration dependence for ATP (apparent Km for ATP = 300 microM for FADH2 synthesis and 6.5 microM for flavokinase), and in the inhibitory effects of riboflavin analogues.", "contents": "Flavokinase and FAD synthetase from Bacillus subtilis specific for reduced flavins. A flavokinase preparation from Bacillus subtilis is described which catalyzes the phosphorylation of reduced, but not oxidized, riboflavin. The enzyme is distinguished from other known flavokinases also in having an unusually low Km for the flavin substrate, 50 to 100 nM. ATP is the obligatory phosphate donor; one ATP is utilized for each FMNH2 formed. Mg2+ or Zn2+ is required for the reaction; Co2+ and Mn2+ will substitute, but less effectively. The same enzyme preparation catalyzes the synthesis of FADH2 from FMNH2 and ATP, but not the synthesis of FAD from FMN and ATP. FADH2 is also formed from reduced riboflavin, presumably by sequential flavokinase and FAD synthetase action. Zn2+ cannot replace Mg2+ in FADH2 formation. The reverse reaction, formation of FMN from FAD, occurs only with reduced FAD, giving rise to FMNH2, and is dependent on the presence of inorganic pyrophosphate. The enzyme thus appears to be an FADH2 pyrophosphorylase. The two enzymatic activities, flavokinase and FADH2 pyrophosphorylase, although not separated during the purification procedure, are distinguished by differences in metal ion specificity, in concentration dependence for ATP (apparent Km for ATP = 300 microM for FADH2 synthesis and 6.5 microM for flavokinase), and in the inhibitory effects of riboflavin analogues."}
{"id": "PMID:226521", "title": "Contribution of alpha helix formation in human plasma apolipoproteins to their enthalpy of association with phospholipids.", "content": "The human plasma apolipoproteins, apo-A-II and apo-C-III, assocaite with phospholipid with a concurrent increase in alpha helical structure of the apoprotein and an exothermic enthalpy of association. A linear correlation of the increase in alpha helical structure and the exothermic enthalpy of association gave a value of -1.3 kcal/mol of amino acid residues converted from a random coil to an alpha helical structure. This value is very close to that of alpha helix formation by charged polyamino acids (-1.2 kcal/mol) and suggests that amino acid side chains contribute little or no heat to the random coil leads to alpha helix transition in the plasma apolipoproteins. In the absence of a change in alpha helix in the apolipoproteins studied here, the enthalpy of association is practically nil, suggesting that alpha helix formation is a major enthalpic contribution to the total free energy of lipid-apolipoprotein association.", "contents": "Contribution of alpha helix formation in human plasma apolipoproteins to their enthalpy of association with phospholipids. The human plasma apolipoproteins, apo-A-II and apo-C-III, assocaite with phospholipid with a concurrent increase in alpha helical structure of the apoprotein and an exothermic enthalpy of association. A linear correlation of the increase in alpha helical structure and the exothermic enthalpy of association gave a value of -1.3 kcal/mol of amino acid residues converted from a random coil to an alpha helical structure. This value is very close to that of alpha helix formation by charged polyamino acids (-1.2 kcal/mol) and suggests that amino acid side chains contribute little or no heat to the random coil leads to alpha helix transition in the plasma apolipoproteins. In the absence of a change in alpha helix in the apolipoproteins studied here, the enthalpy of association is practically nil, suggesting that alpha helix formation is a major enthalpic contribution to the total free energy of lipid-apolipoprotein association."}
{"id": "PMID:226522", "title": "Purification of the T4 gene 32 protein free from detectable deoxyribonuclease activities.", "content": "Detailed procedures are presented which allow reproducible preparation of T4 gene 32 protein, a helix-destabilizing protein essential for DNA replication and genetic recombination in T4 bacteriophage-infected Escherichia coli cells. Although 32 protein can be purified to better than 99% homogeneity by any one of several procedures, these methods have been developed to remove trace amounts of contaminating deoxyribonucleases, which are present in high levels in the original infected cells. Two alternative preparations are presented, each involving three chromatographic steps. Both 32 proteins obtained are essentially \"nuclease-free,\" when tested at physiological salt concentrations. However, we show here that the phenyl-Sepharose chromatography step, which is necessary to remove an exonuclease activity active only at low salt concentrations, also removes a second protein present in trace amounts. In some cases, retention of this second protein is desirable, since it is essential for obtaining RNA primed, de novo DNA chain starts in an in vitro DNA replication system, when this system is constructed by mixing highly purified preparations of each of the six replication proteins coded for by T4 genes 32, 43, 44, 62, 45, and 41.", "contents": "Purification of the T4 gene 32 protein free from detectable deoxyribonuclease activities. Detailed procedures are presented which allow reproducible preparation of T4 gene 32 protein, a helix-destabilizing protein essential for DNA replication and genetic recombination in T4 bacteriophage-infected Escherichia coli cells. Although 32 protein can be purified to better than 99% homogeneity by any one of several procedures, these methods have been developed to remove trace amounts of contaminating deoxyribonucleases, which are present in high levels in the original infected cells. Two alternative preparations are presented, each involving three chromatographic steps. Both 32 proteins obtained are essentially \"nuclease-free,\" when tested at physiological salt concentrations. However, we show here that the phenyl-Sepharose chromatography step, which is necessary to remove an exonuclease activity active only at low salt concentrations, also removes a second protein present in trace amounts. In some cases, retention of this second protein is desirable, since it is essential for obtaining RNA primed, de novo DNA chain starts in an in vitro DNA replication system, when this system is constructed by mixing highly purified preparations of each of the six replication proteins coded for by T4 genes 32, 43, 44, 62, 45, and 41."}
{"id": "PMID:226523", "title": "Azide binding to the cytochrome c ferric heme octapeptide. A model for anion binding to the active site of high spin ferric heme proteins.", "content": "Equilibrium constants for the binding of azide to the ferric heme c octapeptide in 50% ethylene glycol 50% buffer were measured spectrophotometrically. The equilibrium constant for azide binding at 20 degrees C and pH* 7.4 is 29.2, which is approximately 3 to 4 orders of magnitude lower than that observed for azide binding to various ferric hemeproteins. The equilibrium constant was indepent of pH* in the range from 7 to 8. Equilibrium constants at several temperatures exhibited an apparent van't Hoff relationship yielding thermodynamic values of delta H0 = -26,100 J/mol (-6240 cal/mol) and delta S0 = -61.5 J/0K mol (-14.7 e.u.). Comparison of these values to the values for the heme proteins enables one to explain the differences in equiliberium constants in terms of differences in the polarity of the heme environments. The results are consistent with the concept that the oxygen affinity of heme complexes increases with the polarity of the heme environment. The data also suggest that an increase in the polarity of the heme environment should result in a corresponding increase in the susceptibility of ferrous heme dioxygen complexes toward oxidation by the dioxygen.", "contents": "Azide binding to the cytochrome c ferric heme octapeptide. A model for anion binding to the active site of high spin ferric heme proteins. Equilibrium constants for the binding of azide to the ferric heme c octapeptide in 50% ethylene glycol 50% buffer were measured spectrophotometrically. The equilibrium constant for azide binding at 20 degrees C and pH* 7.4 is 29.2, which is approximately 3 to 4 orders of magnitude lower than that observed for azide binding to various ferric hemeproteins. The equilibrium constant was indepent of pH* in the range from 7 to 8. Equilibrium constants at several temperatures exhibited an apparent van't Hoff relationship yielding thermodynamic values of delta H0 = -26,100 J/mol (-6240 cal/mol) and delta S0 = -61.5 J/0K mol (-14.7 e.u.). Comparison of these values to the values for the heme proteins enables one to explain the differences in equiliberium constants in terms of differences in the polarity of the heme environments. The results are consistent with the concept that the oxygen affinity of heme complexes increases with the polarity of the heme environment. The data also suggest that an increase in the polarity of the heme environment should result in a corresponding increase in the susceptibility of ferrous heme dioxygen complexes toward oxidation by the dioxygen."}
{"id": "PMID:226525", "title": "Adenylate cyclase activity and cyclic AMP levels during the development of Dictyostelium discoideum.", "content": "Adenylate cyclase activity and endogenous cyclic AMP levels were measured using a highly sensitive radioimmunoassay and protein binding assay during 24 h of development of Dictyostelium discoideum. Adenylate cyclase activity was not detected until the aggregation stage of development (10 h) when a sudden peak of activity was found. The enzyme was active at all subsequent stages, although a slow decline in activity was observed. Similarly, cyclic AMP levels were not detectable through the first 7 h of development and then showed a sudden peak at aggregation. Following aggregation the cyclic AMP levels decreased to approximately 1/2 the peak value and maintained that level throughout the remainder of the developmental cycle. Adenylate cyclase had a narrow range of substrate saturation with a maximum velocity at 1 to 4 mM ATP at both the aggregation stage (10 h) and the sorocarp stage (24 h). At levels of ATP higher than 6 mM the enzyme from both stages was strongly inhibited. No activity was observed in the absence of Mg2+ or dithiothreitol. The activity from 10-, 14-, and 20-h stages was found bound to a 25,000 x g pellet fraction. The sudden appearance of adenylate cyclase and its product cyclic AMP at aggregation provides additional evidence of a role for this nucleotide in chemotaxis, and the retention of enzyme activity and nucleotide level during the subsequent stages may reflect a further function of cyclic AMP during formation of the two cell types.", "contents": "Adenylate cyclase activity and cyclic AMP levels during the development of Dictyostelium discoideum. Adenylate cyclase activity and endogenous cyclic AMP levels were measured using a highly sensitive radioimmunoassay and protein binding assay during 24 h of development of Dictyostelium discoideum. Adenylate cyclase activity was not detected until the aggregation stage of development (10 h) when a sudden peak of activity was found. The enzyme was active at all subsequent stages, although a slow decline in activity was observed. Similarly, cyclic AMP levels were not detectable through the first 7 h of development and then showed a sudden peak at aggregation. Following aggregation the cyclic AMP levels decreased to approximately 1/2 the peak value and maintained that level throughout the remainder of the developmental cycle. Adenylate cyclase had a narrow range of substrate saturation with a maximum velocity at 1 to 4 mM ATP at both the aggregation stage (10 h) and the sorocarp stage (24 h). At levels of ATP higher than 6 mM the enzyme from both stages was strongly inhibited. No activity was observed in the absence of Mg2+ or dithiothreitol. The activity from 10-, 14-, and 20-h stages was found bound to a 25,000 x g pellet fraction. The sudden appearance of adenylate cyclase and its product cyclic AMP at aggregation provides additional evidence of a role for this nucleotide in chemotaxis, and the retention of enzyme activity and nucleotide level during the subsequent stages may reflect a further function of cyclic AMP during formation of the two cell types."}
{"id": "PMID:226529", "title": "The interferon-induced protein kinase PK-i from mouse L cells.", "content": "Interferon-treated L cells are characterized by an increased protein kinase activity that can selectively phosphorylate the small subunit of eukaryotic initiation factor 2. This protein kinase, PK-i, has been extensively purified and shown to be a potent inhibitor of mRNA translation. The purified PK-i contains the endogenously phosphorylated 67,000 Mr protein characteristic of interferon-treated cell extracts. PK-i can also phosphorylate arginine-rich histones. Purified PK-i can be activated by preincubation with ATP (but not adenylyl imidodiphosphate) and low concentrations of double-stranded RNA. The activation results in an increase in the first rate of eIF-2 phosphorylation. Activated PK-i becomes resistant to high concentrations of double-stranded RNA and more thermostable. A stimulator of PK-i activity, factor A, was isolated, as well as a specific phosphoprotein phosphatase that dephosphorylates the 67,000 Mr protein and eIF-2. These two factors, which are present in untreated L cells, may regulate the translation inhibitory activity of the interferon-induced and double-stranded RNA-activated protein kinase PK-i.", "contents": "The interferon-induced protein kinase PK-i from mouse L cells. Interferon-treated L cells are characterized by an increased protein kinase activity that can selectively phosphorylate the small subunit of eukaryotic initiation factor 2. This protein kinase, PK-i, has been extensively purified and shown to be a potent inhibitor of mRNA translation. The purified PK-i contains the endogenously phosphorylated 67,000 Mr protein characteristic of interferon-treated cell extracts. PK-i can also phosphorylate arginine-rich histones. Purified PK-i can be activated by preincubation with ATP (but not adenylyl imidodiphosphate) and low concentrations of double-stranded RNA. The activation results in an increase in the first rate of eIF-2 phosphorylation. Activated PK-i becomes resistant to high concentrations of double-stranded RNA and more thermostable. A stimulator of PK-i activity, factor A, was isolated, as well as a specific phosphoprotein phosphatase that dephosphorylates the 67,000 Mr protein and eIF-2. These two factors, which are present in untreated L cells, may regulate the translation inhibitory activity of the interferon-induced and double-stranded RNA-activated protein kinase PK-i."}
{"id": "PMID:226536", "title": "The effect of cytochrome P-450cam on the NMR relaxation rate of water protons.", "content": "Cytochrome P-450cam in the native, substrate-free state (Fe3+, S = 1/2) substantially reduces the NMR relaxation times, T1 and T2, of water protons. Temperature and frequency dependences of T1 and T2 were measured; they are consistent with a model of one or two protons exchanging between a binding site on a heme ligand and bulk water. The relevant parameters of this model have been deduced from the data. The spin relaxation time of the heme iron, tau S similar to 0.5 ns at 25 degrees C, is unusually long for a low spin ferric heme protein but is compatible with the line widths measured for paramagnetically shifted heme resonances. The proton residence time on the ligand, tau M similar to 1 microsecond at 25 degrees C, follows an Arrhenius law with activation energy EM similar to 15 kcal/mol. A scalar hyperfine interaction A/h = 2.2 MHz (3.1 MHz for one-proton exchange) of the found proton(s) with the heme iron is deduced from the difference between T1 and T2 observed in the fast exchange limit. The iron-proton distance is found to be 2.9 A (2.6 A for one-proton exchange). Variation of pH between pH 6.4 and 8.6 does not affect T1. The bearing of these results on the question of the axial heme ligand is discussed.", "contents": "The effect of cytochrome P-450cam on the NMR relaxation rate of water protons. Cytochrome P-450cam in the native, substrate-free state (Fe3+, S = 1/2) substantially reduces the NMR relaxation times, T1 and T2, of water protons. Temperature and frequency dependences of T1 and T2 were measured; they are consistent with a model of one or two protons exchanging between a binding site on a heme ligand and bulk water. The relevant parameters of this model have been deduced from the data. The spin relaxation time of the heme iron, tau S similar to 0.5 ns at 25 degrees C, is unusually long for a low spin ferric heme protein but is compatible with the line widths measured for paramagnetically shifted heme resonances. The proton residence time on the ligand, tau M similar to 1 microsecond at 25 degrees C, follows an Arrhenius law with activation energy EM similar to 15 kcal/mol. A scalar hyperfine interaction A/h = 2.2 MHz (3.1 MHz for one-proton exchange) of the found proton(s) with the heme iron is deduced from the difference between T1 and T2 observed in the fast exchange limit. The iron-proton distance is found to be 2.9 A (2.6 A for one-proton exchange). Variation of pH between pH 6.4 and 8.6 does not affect T1. The bearing of these results on the question of the axial heme ligand is discussed."}
{"id": "PMID:226537", "title": "Human hypoxanthine-guanine phosphoribosyltransferase. IMP-GMP exchange stoichiometry and steady state kinetics of the reaction.", "content": "Steady state kinetics of hypoxanthine guanine phosphoribosyltransferase-catalyzed reactions are studied. The results obtained suggest that IMP, GMP, P-Rib-PP, and pyrophosphate bind to the same enzyme form, while hypoxanthine and guanine bind to a different form. Guanine activates IMP-pyrophosphorolysis. During the reaction guanine and IMP are consumed with formation of GM", "contents": "Human hypoxanthine-guanine phosphoribosyltransferase. IMP-GMP exchange stoichiometry and steady state kinetics of the reaction. Steady state kinetics of hypoxanthine guanine phosphoribosyltransferase-catalyzed reactions are studied. The results obtained suggest that IMP, GMP, P-Rib-PP, and pyrophosphate bind to the same enzyme form, while hypoxanthine and guanine bind to a different form. Guanine activates IMP-pyrophosphorolysis. During the reaction guanine and IMP are consumed with formation of GM"}
{"id": "PMID:226538", "title": "Characterization of a calcium-modulated protein from transformed chicken fibroblasts.", "content": "A calcium-modulated protein has been isolated from secondary cultures of virus transformed chicken embryo fibroblasts and has been characterized in terms of its physical, chemical, and functional properties. These properties demonstrate that this protein is a calmodulin and distinguish it from other calcium-modulated proteins found in various muscle and non-muscle tissues. In addition, this transformed cell calmodulin has been shown to be indistinguishable in both structure and function from normal cell calmodulins isolated from chicken gizzard and brain. A novel change in the electrophoretic behavior of these calmodulin preparations that is dependent on sample history has been observed. These alterations may be the basis for previous reports of tissue specific differences in calmodulin and for some of the differences occasionally observed in peptide maps of calmodulins.", "contents": "Characterization of a calcium-modulated protein from transformed chicken fibroblasts. A calcium-modulated protein has been isolated from secondary cultures of virus transformed chicken embryo fibroblasts and has been characterized in terms of its physical, chemical, and functional properties. These properties demonstrate that this protein is a calmodulin and distinguish it from other calcium-modulated proteins found in various muscle and non-muscle tissues. In addition, this transformed cell calmodulin has been shown to be indistinguishable in both structure and function from normal cell calmodulins isolated from chicken gizzard and brain. A novel change in the electrophoretic behavior of these calmodulin preparations that is dependent on sample history has been observed. These alterations may be the basis for previous reports of tissue specific differences in calmodulin and for some of the differences occasionally observed in peptide maps of calmodulins."}
{"id": "PMID:226541", "title": "5'-Hydroxyl polyribonucleotide kinase from HeLa cell nuclei. Purification and properties.", "content": "An enzyme, 5'-hydroxyl polyribonucleotide kinase, which catalyzes the phosphorylation of 5'-hydroxyl ends of RNA in the presence of ATP, has been isolated from extracts of HeLa cell nuclei. The kinase requires a divalent cation (Mg2+ or Mn2+) for activity, has an alkaline pH optimum, and is sensitive to the sulfhydryl antagonist N-ethylmaleimide. 5'-hydroxyl terminated polydeoxyribonucleotides are phosphorylated much less efficiently than the 5'-hydroxyl terminated polyribonucleotides, and the kinase preparation is inactive on ribonucleoside 3'-monophosphates. Enzyme activity is inhibited by ADP and by pyrophosphate. The sedimentation coefficient of the kinase is estimated to be 5.6 S from glycerol gradient centrifugation.", "contents": "5'-Hydroxyl polyribonucleotide kinase from HeLa cell nuclei. Purification and properties. An enzyme, 5'-hydroxyl polyribonucleotide kinase, which catalyzes the phosphorylation of 5'-hydroxyl ends of RNA in the presence of ATP, has been isolated from extracts of HeLa cell nuclei. The kinase requires a divalent cation (Mg2+ or Mn2+) for activity, has an alkaline pH optimum, and is sensitive to the sulfhydryl antagonist N-ethylmaleimide. 5'-hydroxyl terminated polydeoxyribonucleotides are phosphorylated much less efficiently than the 5'-hydroxyl terminated polyribonucleotides, and the kinase preparation is inactive on ribonucleoside 3'-monophosphates. Enzyme activity is inhibited by ADP and by pyrophosphate. The sedimentation coefficient of the kinase is estimated to be 5.6 S from glycerol gradient centrifugation."}
{"id": "PMID:226542", "title": "Phosphorylation of 5-iodo-5'-amino-2',5',dideoxyuridine by herpes simplex virus type 1 encoded thymidine kinase.", "content": "Herpes simplex virus type 1 (HSV-1) encoded thymidine kinase converts 5-iodo-5'-amino-2',5'-dideoxyuridine (AIdUrd), a highly specific anti-herpes agent, into the 5'-diphosphate (AIdUDP) derivative in vitro. AIdUDP was identified by its acid lability, sensitivity to alkaline phosphatase hydrolysis, chromatographic behavior, and ratio of double isotope (125I, 32P) labeling. ATP, but not AMP, is a phosphate donor, and the direct transfer of the beta and gamma phosphate of ATP as pyrophosphate to AIdUrd was ruled out. The presence of a phosphoramidate bond was supported by the acid lability of AIdUDP which has a half life (t1/2) of 320 min at pH 3.0. At neutral pH, the hydrolysis products are AIdUrd and orthophosphate, with AIdUrd monophosphate being the probable hydrolytic intermediate at these pH values. However, at acidic pH, some pyrophosphate was detected in addition to AIdUrd and orthophosphate. AIdUrd competitively inhibited the phosphorylation of thymidine and deoxycytidine. Escherichia coli thymidine kinase, even though 100-fold higher in activity, was unable to phosphorylate AId-Urd under similar incubation conditions.", "contents": "Phosphorylation of 5-iodo-5'-amino-2',5',dideoxyuridine by herpes simplex virus type 1 encoded thymidine kinase. Herpes simplex virus type 1 (HSV-1) encoded thymidine kinase converts 5-iodo-5'-amino-2',5'-dideoxyuridine (AIdUrd), a highly specific anti-herpes agent, into the 5'-diphosphate (AIdUDP) derivative in vitro. AIdUDP was identified by its acid lability, sensitivity to alkaline phosphatase hydrolysis, chromatographic behavior, and ratio of double isotope (125I, 32P) labeling. ATP, but not AMP, is a phosphate donor, and the direct transfer of the beta and gamma phosphate of ATP as pyrophosphate to AIdUrd was ruled out. The presence of a phosphoramidate bond was supported by the acid lability of AIdUDP which has a half life (t1/2) of 320 min at pH 3.0. At neutral pH, the hydrolysis products are AIdUrd and orthophosphate, with AIdUrd monophosphate being the probable hydrolytic intermediate at these pH values. However, at acidic pH, some pyrophosphate was detected in addition to AIdUrd and orthophosphate. AIdUrd competitively inhibited the phosphorylation of thymidine and deoxycytidine. Escherichia coli thymidine kinase, even though 100-fold higher in activity, was unable to phosphorylate AId-Urd under similar incubation conditions."}
{"id": "PMID:226543", "title": "Dispersed mammary epithelial cells. Receptors of lactogenic hormones in virgin, pregnant, and lactating rabbits.", "content": "The number and affinity of binding sites for lactogenic hormones have been determined in dispersed mammary cells from virgin, pregnant, and lactating rabbits. Dispersed epithelial cells, prepared from mammary glands by enzyme digestion, calcium chelation, and gentle shearing, were separated from nonepithelial cells by density centrifugation. 125I-labeled ovine prolactin (oPRL) and 125I-labeled human growth hormone (/GH) were used as tracers. Association and dissociation of 125I-oPRL or 125I-hGH were time- and temperature-dependent. The rate of association followed a second order reversible reaction with a rate constant of approximately 0.5 at 4 degrees C, approximately 2.0 at 23 degrees C, and approximately 9 x 10(7) M-1 min-1 at 37 degrees C. Maximum binding was achieved after 120 h at 4 degrees C, 48 h at 23 degrees C, and 2 to 4 h at 37 degrees C. Dissociation of 125I-oPRL or hGH from cells by unlabeled oPRL was complete at 4 degrees C after 160 h, following a first order reaction (5-1 = 9.9 x 10(-5) min) and incomplete at 23 degrees C and 37 degrees C even after prolonged time. Internalization of receptor-bound 125I-oPRL was studied by quantitative electron microscope autoradiography. Grain distribution over- and volume densities of cellular organelles was analyzed as a function of time and temperature. At 37 degrees C, there was a rapid and specific translocation of lactogenic hormones to intracellular organelles. Autoradiographic grains were found associated with vesicles, Golgi elements, lysosome-like structures, and the nucleus. One class of high affinity binding sites was estimated from Scatchard plot and direct kinetic analyses at 4 degrees C. Whereas the apparent affinity constant (approximately 10(10) M-1) did not change significantly throughout pregnancy and early lactation, the number of receptors extrapolated from Scatchard plots at 4 degrees C varied in an inverse relation to serum progesterone concentration. Thus, approximately 1900 sites were detected in virgin rabbits (progesterone, approximately 200 pg/ml), and midpregnancy (progesterone, approximately 15,000 pg/ml), and approximately 1800 during early lactation (progesterone, approximately 500 pg/ml). The binding properties of lactogenic hormones to dispersed cells was compared with those to Triton X-100 solubilized microsomal membrane preparations. Good correlation between the two systems was found indicating that cell dispersion did not alter binding properties. Our results indicate that dispersed mammary cells bind lactogenic hormones in a saturable and reversible process, that the number of exposed receptors varies throughout gestation and lactation, and finally that lactogenic hormones are internalized following interaction with their membrane receptors.", "contents": "Dispersed mammary epithelial cells. Receptors of lactogenic hormones in virgin, pregnant, and lactating rabbits. The number and affinity of binding sites for lactogenic hormones have been determined in dispersed mammary cells from virgin, pregnant, and lactating rabbits. Dispersed epithelial cells, prepared from mammary glands by enzyme digestion, calcium chelation, and gentle shearing, were separated from nonepithelial cells by density centrifugation. 125I-labeled ovine prolactin (oPRL) and 125I-labeled human growth hormone (/GH) were used as tracers. Association and dissociation of 125I-oPRL or 125I-hGH were time- and temperature-dependent. The rate of association followed a second order reversible reaction with a rate constant of approximately 0.5 at 4 degrees C, approximately 2.0 at 23 degrees C, and approximately 9 x 10(7) M-1 min-1 at 37 degrees C. Maximum binding was achieved after 120 h at 4 degrees C, 48 h at 23 degrees C, and 2 to 4 h at 37 degrees C. Dissociation of 125I-oPRL or hGH from cells by unlabeled oPRL was complete at 4 degrees C after 160 h, following a first order reaction (5-1 = 9.9 x 10(-5) min) and incomplete at 23 degrees C and 37 degrees C even after prolonged time. Internalization of receptor-bound 125I-oPRL was studied by quantitative electron microscope autoradiography. Grain distribution over- and volume densities of cellular organelles was analyzed as a function of time and temperature. At 37 degrees C, there was a rapid and specific translocation of lactogenic hormones to intracellular organelles. Autoradiographic grains were found associated with vesicles, Golgi elements, lysosome-like structures, and the nucleus. One class of high affinity binding sites was estimated from Scatchard plot and direct kinetic analyses at 4 degrees C. Whereas the apparent affinity constant (approximately 10(10) M-1) did not change significantly throughout pregnancy and early lactation, the number of receptors extrapolated from Scatchard plots at 4 degrees C varied in an inverse relation to serum progesterone concentration. Thus, approximately 1900 sites were detected in virgin rabbits (progesterone, approximately 200 pg/ml), and midpregnancy (progesterone, approximately 15,000 pg/ml), and approximately 1800 during early lactation (progesterone, approximately 500 pg/ml). The binding properties of lactogenic hormones to dispersed cells was compared with those to Triton X-100 solubilized microsomal membrane preparations. Good correlation between the two systems was found indicating that cell dispersion did not alter binding properties. Our results indicate that dispersed mammary cells bind lactogenic hormones in a saturable and reversible process, that the number of exposed receptors varies throughout gestation and lactation, and finally that lactogenic hormones are internalized following interaction with their membrane receptors."}
{"id": "PMID:226544", "title": "Requirements for synthesis of ribonucleic acid primers during lagging strand synthesis by the DNA polymerase and gene 4 protein of bacteriophage T7.", "content": "DNA polymerase and gene 4 protein of bacteriophage T7 catalyze DNA synthesis on duplex DNA templates. Synthesis is initiated at nicks in the DNA template, and this leading strand synthesis results in displacement of one of the parental strands. In the presence of ribonucleoside 5'-triphosphates the gene 4 protein catalyzes the synthesis of oligoribonucleotide primers on the displaced single strand, and their extension by T7 dna polymerase accounts for lagging strand synthesis. Since all the oligoribonucleotide primers bear adenosine 5'-triphosphate residues at their 5' termini, [gamma 32P]ATP is incorporated specifically into the product molecule, thus providing a rapid and sensitive assay for the synthesis of the RNA primers. Both primer synthesis and DNA synthesis are stimulated 3- to 5-fold by the presence of either Escherichia coli or T7 helix-destabilizing protein (DNA binding protein). ATP and CTP together fully satisfy the requirement for rNTPs and provide maximum synthesis of primers and DNA. Provided that T7 DNA polymerase is present, RNA-primed DNA synthesis occurs on either duplex or single-stranded DNA templates and to equal extents on either strand of T7 DNA. No primer-directed DNA synthesis occurs on poly(dT) or poly(dG) templates, indicating that synthesis of primers is template-directed.", "contents": "Requirements for synthesis of ribonucleic acid primers during lagging strand synthesis by the DNA polymerase and gene 4 protein of bacteriophage T7. DNA polymerase and gene 4 protein of bacteriophage T7 catalyze DNA synthesis on duplex DNA templates. Synthesis is initiated at nicks in the DNA template, and this leading strand synthesis results in displacement of one of the parental strands. In the presence of ribonucleoside 5'-triphosphates the gene 4 protein catalyzes the synthesis of oligoribonucleotide primers on the displaced single strand, and their extension by T7 dna polymerase accounts for lagging strand synthesis. Since all the oligoribonucleotide primers bear adenosine 5'-triphosphate residues at their 5' termini, [gamma 32P]ATP is incorporated specifically into the product molecule, thus providing a rapid and sensitive assay for the synthesis of the RNA primers. Both primer synthesis and DNA synthesis are stimulated 3- to 5-fold by the presence of either Escherichia coli or T7 helix-destabilizing protein (DNA binding protein). ATP and CTP together fully satisfy the requirement for rNTPs and provide maximum synthesis of primers and DNA. Provided that T7 DNA polymerase is present, RNA-primed DNA synthesis occurs on either duplex or single-stranded DNA templates and to equal extents on either strand of T7 DNA. No primer-directed DNA synthesis occurs on poly(dT) or poly(dG) templates, indicating that synthesis of primers is template-directed."}
{"id": "PMID:226545", "title": "Characterization of the ribonucleic acid primers and the deoxyribonucleic acid product synthesized by the DNA polymerase and gene 4 protein of bacteriophage T7.", "content": "The DNA polymerase and gene 4 protein of phage T7, in the presence of helix-destabilizing protein (DNA binding protein), catalyze DNA synthesis on duplex templates. As has been previously shown (Kolodner, R. D., and Richardson, C. C. (1978) 4. Biol. Chem. 253, 574-584), in the absence of ribonucleoside 5'-triphosphates DNA synthesis is initiated at nicks, and all of the newly synthesized DNA is covalently attached to the template. In this paper we characterize the DNA synthesized in the presence of ribonucleoside 5'-triphophates and show that, in contrast, the major portion of the newly synthesized DNA is not attached to the template, having an average chain length of 5000 to 6000 nucleotides. In addition, each chain of newly synthesized DNA is terminated at its 5'-end by a covalently attached tetranucleotide RNA primer whose sequence is predominantly pppApCpCpC and pppApCpCpA. The results of isotope transfer experiments are in agreement with the number of initiation events determined by the incorporation of [gamma-32P]ATP and indicate that each of the four deoxyribonucleotides is present at the RNA-DNA junction.", "contents": "Characterization of the ribonucleic acid primers and the deoxyribonucleic acid product synthesized by the DNA polymerase and gene 4 protein of bacteriophage T7. The DNA polymerase and gene 4 protein of phage T7, in the presence of helix-destabilizing protein (DNA binding protein), catalyze DNA synthesis on duplex templates. As has been previously shown (Kolodner, R. D., and Richardson, C. C. (1978) 4. Biol. Chem. 253, 574-584), in the absence of ribonucleoside 5'-triphosphates DNA synthesis is initiated at nicks, and all of the newly synthesized DNA is covalently attached to the template. In this paper we characterize the DNA synthesized in the presence of ribonucleoside 5'-triphophates and show that, in contrast, the major portion of the newly synthesized DNA is not attached to the template, having an average chain length of 5000 to 6000 nucleotides. In addition, each chain of newly synthesized DNA is terminated at its 5'-end by a covalently attached tetranucleotide RNA primer whose sequence is predominantly pppApCpCpC and pppApCpCpA. The results of isotope transfer experiments are in agreement with the number of initiation events determined by the incorporation of [gamma-32P]ATP and indicate that each of the four deoxyribonucleotides is present at the RNA-DNA junction."}
{"id": "PMID:226547", "title": "Isolation and characterization of the transferrin receptor from human placenta.", "content": "The transferrin receptor has been isolated from human placenta using immunochromatography and affinity chromatography. The receptor is a glycoprotein and has a Mr = 90,000 on sodium dodecyl sulfate-gel electrophoresis in the presence of 2-mercaptoethanol. The isolated receptor is immunologically related to the transferrin receptor on the reticulocyte cell surface.", "contents": "Isolation and characterization of the transferrin receptor from human placenta. The transferrin receptor has been isolated from human placenta using immunochromatography and affinity chromatography. The receptor is a glycoprotein and has a Mr = 90,000 on sodium dodecyl sulfate-gel electrophoresis in the presence of 2-mercaptoethanol. The isolated receptor is immunologically related to the transferrin receptor on the reticulocyte cell surface."}
{"id": "PMID:226548", "title": "Adenosine 3':5'-monophosphate-mediated inhibition of myosin light chain phosphorylation in bovine aortic actomyosin.", "content": "Ca2+-dependent phosphorylation of the myosin light chains in bovine aortic native actomyosin is markedly depressed in the presence of cyclic AMP and its dependent protein kinase. This inhibition occurs with either cardiac, skeletal, or aortic protein kinase plus cyclic AMP, while little or no inhibition occurs with either cyclic AMP or protein kinase alone. The extent of inhibition is related to the concentration of protein kinase and approaches a maximum of approximately 50%. Concomitant with the inhibition of myosin light chain phosphorylation is (a) an increased phosphorylation of a 100,000-dalton moiety which possibly corresponds to the myosin light chain kinase present in the native actomyosin preparation and (b) a decrease in the actomyosin Mg2+-ATPase activity. These findings suggest that modulation of actin-myosin interactions by the cAMP system directly at the level of the contractile proteins may represent a mechanism by which beta adrenergic relaxation occurs in mammalian vascular smooth muscle.", "contents": "Adenosine 3':5'-monophosphate-mediated inhibition of myosin light chain phosphorylation in bovine aortic actomyosin. Ca2+-dependent phosphorylation of the myosin light chains in bovine aortic native actomyosin is markedly depressed in the presence of cyclic AMP and its dependent protein kinase. This inhibition occurs with either cardiac, skeletal, or aortic protein kinase plus cyclic AMP, while little or no inhibition occurs with either cyclic AMP or protein kinase alone. The extent of inhibition is related to the concentration of protein kinase and approaches a maximum of approximately 50%. Concomitant with the inhibition of myosin light chain phosphorylation is (a) an increased phosphorylation of a 100,000-dalton moiety which possibly corresponds to the myosin light chain kinase present in the native actomyosin preparation and (b) a decrease in the actomyosin Mg2+-ATPase activity. These findings suggest that modulation of actin-myosin interactions by the cAMP system directly at the level of the contractile proteins may represent a mechanism by which beta adrenergic relaxation occurs in mammalian vascular smooth muscle."}
{"id": "PMID:226549", "title": "Stereochemistry of hydrolysis of adenosine 3':5'-cyclic phosphorothioate by the cyclic phosphodiesterase from beef heart.", "content": "Adenosine 3':5'-cyclic phosphorothioate, Sp-diastereomer was hydrolyzed by cyclic phosphodiesterase from beef heart in the presence of [18O]water to [18O]adenosine 5'-phosphorothioate. This was phosphorylated by myokinase and pyruvate kinase to [18O]adenosine 5'-(1-thiotriphosphate),Sp-diastereomer. The position of 18O was determined to be in a nonbridging position. This result indicates that the hydrolysis proceeded with inversion of configuration at phosphorus.", "contents": "Stereochemistry of hydrolysis of adenosine 3':5'-cyclic phosphorothioate by the cyclic phosphodiesterase from beef heart. Adenosine 3':5'-cyclic phosphorothioate, Sp-diastereomer was hydrolyzed by cyclic phosphodiesterase from beef heart in the presence of [18O]water to [18O]adenosine 5'-phosphorothioate. This was phosphorylated by myokinase and pyruvate kinase to [18O]adenosine 5'-(1-thiotriphosphate),Sp-diastereomer. The position of 18O was determined to be in a nonbridging position. This result indicates that the hydrolysis proceeded with inversion of configuration at phosphorus."}
{"id": "PMID:226550", "title": "Cytochrome c oxidase subunits in contact with phospholipids. Hydrophobic photolabeling with azidophospholipids.", "content": "The technique of photolabeling of membrane proteins with arylazidophospholipids was applied to cytochrome c oxidase. The \"deep\" and \"shallow\" labels employed reacted with all subunits of cytochrome c oxidase except V and VI: Subunits I, III, and VII were heavily labeled, Subunit II was labeled to a lesser extent, and Subunit IV was poorly labeled. Subunit I was labeled more by the deep label and Subunit VII by the shallow one. The other subunits were equally labeled by the two probes. This technique has revealed what subunits of cytochrome c oxidase interact with the lipid and their approximate position in the membrane.", "contents": "Cytochrome c oxidase subunits in contact with phospholipids. Hydrophobic photolabeling with azidophospholipids. The technique of photolabeling of membrane proteins with arylazidophospholipids was applied to cytochrome c oxidase. The \"deep\" and \"shallow\" labels employed reacted with all subunits of cytochrome c oxidase except V and VI: Subunits I, III, and VII were heavily labeled, Subunit II was labeled to a lesser extent, and Subunit IV was poorly labeled. Subunit I was labeled more by the deep label and Subunit VII by the shallow one. The other subunits were equally labeled by the two probes. This technique has revealed what subunits of cytochrome c oxidase interact with the lipid and their approximate position in the membrane."}
{"id": "PMID:226554", "title": "Inhibition of low density lipoprotein uptake in confluent endothelial cell monolayers correlates with a restricted surface receptor redistribution.", "content": "Binding of either low density lipoprotein (LDL) or Concanavalin A (ConA) to actively growing vascular endothelial cells is associated with a redistrubution of the appropriate cell surface receptor sites which form patches and caps. This receptor lateral mobility is greatly restricted when endothelial cells reach confluence and adopt the configuration of a cell monolayer composed of closely apposed and non-overlapping cells. In this case, although the cells still exhibit specific LDL binding to the appropriate cell surface receptor sites, neither the binding of LDL nor of ConA induces a receptor redistribution. The lack of LDL receptor redistribution correlates with a marked decrease in the rate of LDL internalization. In contrast, no such density-dependent changes are observed in cell types which grow on top of each other and form multiple cell layers at confluence. Thus, neither LDL nor ConA induced cap formation in either sparse or confluent smooth muscle cell cultures and the same rate of LDL internalization is observed at both cell densities. Similarly, adsorptive endocytosis of cationized LDL (which enters the cells independently of the LDL receptor sites) was not correlated with a detectable receptor redistribution, nor was it significantly affected by changes in cell density and spatial organization. The formation of a confluent cell monolayer resting on an underlying basement membrane might therefore provide, via a change in membrane dynamics, a mechanism whereby the endothelium of large blood vessels can function as a protective barrier against the high circulating levels of LDL in plasma.", "contents": "Inhibition of low density lipoprotein uptake in confluent endothelial cell monolayers correlates with a restricted surface receptor redistribution. Binding of either low density lipoprotein (LDL) or Concanavalin A (ConA) to actively growing vascular endothelial cells is associated with a redistrubution of the appropriate cell surface receptor sites which form patches and caps. This receptor lateral mobility is greatly restricted when endothelial cells reach confluence and adopt the configuration of a cell monolayer composed of closely apposed and non-overlapping cells. In this case, although the cells still exhibit specific LDL binding to the appropriate cell surface receptor sites, neither the binding of LDL nor of ConA induces a receptor redistribution. The lack of LDL receptor redistribution correlates with a marked decrease in the rate of LDL internalization. In contrast, no such density-dependent changes are observed in cell types which grow on top of each other and form multiple cell layers at confluence. Thus, neither LDL nor ConA induced cap formation in either sparse or confluent smooth muscle cell cultures and the same rate of LDL internalization is observed at both cell densities. Similarly, adsorptive endocytosis of cationized LDL (which enters the cells independently of the LDL receptor sites) was not correlated with a detectable receptor redistribution, nor was it significantly affected by changes in cell density and spatial organization. The formation of a confluent cell monolayer resting on an underlying basement membrane might therefore provide, via a change in membrane dynamics, a mechanism whereby the endothelium of large blood vessels can function as a protective barrier against the high circulating levels of LDL in plasma."}
{"id": "PMID:226555", "title": "Regulation of cyclic nucleotide phosphodiesterase forms by serum and insulin in cultured fibroblasts.", "content": "A rapid reduction of cyclic nucleotide phosphodiesterase activity occurs after the replating of confluent cultures of BHK 21 c/13 fibroblasts into fresh medium. This reduction in activity depends on the density to which the cultures are reseeded and the concentration of serum in the medium. Enzyme activity in BHK cells is restored after 24 to 48 hours if cells are diluted into medium containing 10% fetal calf serum or 0.5% fetal calf serum supplemented with insulin (10(-6)M), but not into 0.5% serum alone. The restoration in enzyme activity is blocked by cycloheximide or Actinomycin D. When BHK cells become quiescent by maintanance in 0.5% serum conditions for 48 hours, a rapid (15--60 minutes) increase in cyclic AMP phosphodiesterase activity occurs when 10% serum is added to the cultures. Enzyme activity is increased even further after 24 to 48 hours in the 10% serum. Cycloheximide or Actinomycin D do not affect the rapid increase in enzyme activity in response to serum, but completely inhibit the long term increase. In contrast to serum, insulin (10(-8) to 10(-6)M) has no short term effect, but does increase enzyme activity after 24 to 48 hours to levels comparable to those seen with addition of 10% serum. As is the case with serum, this long term effect of insulin on enzyme activity is prevented by inhibitors of protein and RNA synthesis. Kinetic analyses of cyclic AMP phosphodiesterase activity in homogenates of quiescent BHK cells indicate the presence of only high Km (congruent to 20 muM) enzyme activity. Addition of serum or insulin to quiescent cells results in the appearance of apparent low Km enzyme activity in homogenates. Sucrose gradient analysis of BHK cells displays two forms of cyclic AMP phosphodiesterase enzyme activity: a 3--4 S form and 5--6 S form. In quiescent cells, the 5--6 S form greatly predominates relative to the 3--4 S form. Addition of serum to quiescent cells results in a rapid appearance of increased 3--4 S form enzyme activity. Insulin also increases the activity of this higher affinity 3--4 S enzyme form after 24 to 48 hours in culture. The functional significance of short and long term regulation of cyclic nucleotide phosphodiesterase(s) in cells is discussed.", "contents": "Regulation of cyclic nucleotide phosphodiesterase forms by serum and insulin in cultured fibroblasts. A rapid reduction of cyclic nucleotide phosphodiesterase activity occurs after the replating of confluent cultures of BHK 21 c/13 fibroblasts into fresh medium. This reduction in activity depends on the density to which the cultures are reseeded and the concentration of serum in the medium. Enzyme activity in BHK cells is restored after 24 to 48 hours if cells are diluted into medium containing 10% fetal calf serum or 0.5% fetal calf serum supplemented with insulin (10(-6)M), but not into 0.5% serum alone. The restoration in enzyme activity is blocked by cycloheximide or Actinomycin D. When BHK cells become quiescent by maintanance in 0.5% serum conditions for 48 hours, a rapid (15--60 minutes) increase in cyclic AMP phosphodiesterase activity occurs when 10% serum is added to the cultures. Enzyme activity is increased even further after 24 to 48 hours in the 10% serum. Cycloheximide or Actinomycin D do not affect the rapid increase in enzyme activity in response to serum, but completely inhibit the long term increase. In contrast to serum, insulin (10(-8) to 10(-6)M) has no short term effect, but does increase enzyme activity after 24 to 48 hours to levels comparable to those seen with addition of 10% serum. As is the case with serum, this long term effect of insulin on enzyme activity is prevented by inhibitors of protein and RNA synthesis. Kinetic analyses of cyclic AMP phosphodiesterase activity in homogenates of quiescent BHK cells indicate the presence of only high Km (congruent to 20 muM) enzyme activity. Addition of serum or insulin to quiescent cells results in the appearance of apparent low Km enzyme activity in homogenates. Sucrose gradient analysis of BHK cells displays two forms of cyclic AMP phosphodiesterase enzyme activity: a 3--4 S form and 5--6 S form. In quiescent cells, the 5--6 S form greatly predominates relative to the 3--4 S form. Addition of serum to quiescent cells results in a rapid appearance of increased 3--4 S form enzyme activity. Insulin also increases the activity of this higher affinity 3--4 S enzyme form after 24 to 48 hours in culture. The functional significance of short and long term regulation of cyclic nucleotide phosphodiesterase(s) in cells is discussed."}
{"id": "PMID:226556", "title": "A variant of S49 mouse lymphoma cells with enhanced secretion of cyclic AMP.", "content": "A novel variant of S49 mouse lymphoma cells is described which is resistant to growth arrest and cytolysis by dibutyryl cyclic AMP but, in contrast to previously described variants, has normal cyclic AMP-dependent protein kinase. The variant is also resistant to N6-monobutyryl cAMP but is sensitive to killing by 8-bromo cAMP and cholera toxin. Extracts of the variant appear to contain wild type levels of both O2'-butyrylesterase and cyclic AMP phosphodiesterase activities. Accumulation of exogenous [3H]dibutyryl cyclic AMP is reduced in the variant suggesting a defect in either uptake or secretion of the analog or its metabolic products. Accumulation of cyclic AMP in variant cells after stimulation of adenylate cyclase with either isoproterenol or cholera toxin is also reduced compared with wild type cells, although cyclase activity of membranes prepared from the variant cells is normal. Extracellular accumulation of cyclic AMP after stimulation of variant cells with isoproterenol is greater than that found with wild type cells. It is concluded that the variant has an alteration in its cyclic AMP secretion mechanism resulting in more efficient extrusion of cyclic AMP than in wild type cells.", "contents": "A variant of S49 mouse lymphoma cells with enhanced secretion of cyclic AMP. A novel variant of S49 mouse lymphoma cells is described which is resistant to growth arrest and cytolysis by dibutyryl cyclic AMP but, in contrast to previously described variants, has normal cyclic AMP-dependent protein kinase. The variant is also resistant to N6-monobutyryl cAMP but is sensitive to killing by 8-bromo cAMP and cholera toxin. Extracts of the variant appear to contain wild type levels of both O2'-butyrylesterase and cyclic AMP phosphodiesterase activities. Accumulation of exogenous [3H]dibutyryl cyclic AMP is reduced in the variant suggesting a defect in either uptake or secretion of the analog or its metabolic products. Accumulation of cyclic AMP in variant cells after stimulation of adenylate cyclase with either isoproterenol or cholera toxin is also reduced compared with wild type cells, although cyclase activity of membranes prepared from the variant cells is normal. Extracellular accumulation of cyclic AMP after stimulation of variant cells with isoproterenol is greater than that found with wild type cells. It is concluded that the variant has an alteration in its cyclic AMP secretion mechanism resulting in more efficient extrusion of cyclic AMP than in wild type cells."}
{"id": "PMID:226557", "title": "Quantitative analysis of vitamin D3 in a feed using normal phase high pressure liquid chromatography.", "content": "A procedure is described for the separation and quantification of Vitamin D3 from different feeds and premixes. The study was conducted, first using a liquid partition step as a preliminary clean-up after extraction, then chromatography on activated Silica gel 60 before final analysis on a high pressure liquid chromatograph (HPLC) using a LiChrosorb NH2 (10 mu) column and a variable wavelength UV detector set at 264 nm. Total analysis on the HPLC was achieved in fifteen minutes. The detector response curve for an authentic D3 standard was linear using peak areas with a minimum detectable amount being 5 ng. The overall percent recovery of D3 in feeds was 94.4 +/- 2.4%. The minimum detectable amount of D3 in animal feeds was found to be in the region of 2,000 I.U./kg.", "contents": "Quantitative analysis of vitamin D3 in a feed using normal phase high pressure liquid chromatography. A procedure is described for the separation and quantification of Vitamin D3 from different feeds and premixes. The study was conducted, first using a liquid partition step as a preliminary clean-up after extraction, then chromatography on activated Silica gel 60 before final analysis on a high pressure liquid chromatograph (HPLC) using a LiChrosorb NH2 (10 mu) column and a variable wavelength UV detector set at 264 nm. Total analysis on the HPLC was achieved in fifteen minutes. The detector response curve for an authentic D3 standard was linear using peak areas with a minimum detectable amount being 5 ng. The overall percent recovery of D3 in feeds was 94.4 +/- 2.4%. The minimum detectable amount of D3 in animal feeds was found to be in the region of 2,000 I.U./kg."}
{"id": "PMID:226558", "title": "Interaction between thyroid-stimulating immunoglobulins and thyrotropin receptors in fat cell membranes.", "content": "In the TSH radioreceptor assay to study the interaction between Graves' immunoglobulins (Ig) and TSH receptors in guinea pig fat cell membranes, Graves' Ig were found to inhibit [125I]TSH binding to fat cell membranes in a dose-dependent manner. Scatchard analysis of [125I]TSH displacement curves by Graves' Ig indicated a single population of the binding sites in fat cell membranes, in contrast to two populations of TSH-binding sites in the membranes. Displacement of [125I]TSH bound to fat cell membranes by both Graves' Ig and unlabeled TSH were time and temperature dependent, with similar dissociation curves, suggesting a specific binding of Graves' Ig to the membrane sites related to the TSH receptor in the fat cells. Such Ig are referred to as fat cell-binding Ig, to be distinguished from the thyroid-stimulating Ig (TSI) detected by TSH radioreceptor assay using human thyroid membranes. Both fat cell-binding Ig and TSI were detected in the sera of a great majority of untreated patients with Graves' disease. A significant correlation was found between both values (r = 0.80; n = 19; P less than 0.001). According to these results, TSI might represent an autoantibody to the membranes associated with the TSH receptor of the target tissues without a strict organ specificity.", "contents": "Interaction between thyroid-stimulating immunoglobulins and thyrotropin receptors in fat cell membranes. In the TSH radioreceptor assay to study the interaction between Graves' immunoglobulins (Ig) and TSH receptors in guinea pig fat cell membranes, Graves' Ig were found to inhibit [125I]TSH binding to fat cell membranes in a dose-dependent manner. Scatchard analysis of [125I]TSH displacement curves by Graves' Ig indicated a single population of the binding sites in fat cell membranes, in contrast to two populations of TSH-binding sites in the membranes. Displacement of [125I]TSH bound to fat cell membranes by both Graves' Ig and unlabeled TSH were time and temperature dependent, with similar dissociation curves, suggesting a specific binding of Graves' Ig to the membrane sites related to the TSH receptor in the fat cells. Such Ig are referred to as fat cell-binding Ig, to be distinguished from the thyroid-stimulating Ig (TSI) detected by TSH radioreceptor assay using human thyroid membranes. Both fat cell-binding Ig and TSI were detected in the sera of a great majority of untreated patients with Graves' disease. A significant correlation was found between both values (r = 0.80; n = 19; P less than 0.001). According to these results, TSI might represent an autoantibody to the membranes associated with the TSH receptor of the target tissues without a strict organ specificity."}
{"id": "PMID:226559", "title": "Plasma high density lipoprotein cholesterol in thyroid disease.", "content": "The plasma levels of high density lipoprotein cholesterol (HDL-C) were reduced in 16 hyperthyroid female patients compared to 37 euthyroid women (33.5 +/- 8 vs. 51.5 +/- 13 mg/dl (mean +/- SD); P less than 0.001). When 5 patients were restudied after restoration of the euthyroid state, plasma HDL-C increased from 29 +/- 5 to 43 +/- 11.5 mg/dl (P less than 0.05). In addition, in 22 hypothyroid women, HDL-C levels were also diminished compared to the euthyroid group (43.4 +/- 15.5 vs. 51.5 +/- 13 mg/dl; P less than 0.05). Nine patients were restudied after L-T4 replacement therapy; their levels of HDL-C increased but not to a statistically significant degree. The daily administration of 0.3 mg L-T4 to eight normal male volunteers for 1 month did not significantly affect HDL-C levels.", "contents": "Plasma high density lipoprotein cholesterol in thyroid disease. The plasma levels of high density lipoprotein cholesterol (HDL-C) were reduced in 16 hyperthyroid female patients compared to 37 euthyroid women (33.5 +/- 8 vs. 51.5 +/- 13 mg/dl (mean +/- SD); P less than 0.001). When 5 patients were restudied after restoration of the euthyroid state, plasma HDL-C increased from 29 +/- 5 to 43 +/- 11.5 mg/dl (P less than 0.05). In addition, in 22 hypothyroid women, HDL-C levels were also diminished compared to the euthyroid group (43.4 +/- 15.5 vs. 51.5 +/- 13 mg/dl; P less than 0.05). Nine patients were restudied after L-T4 replacement therapy; their levels of HDL-C increased but not to a statistically significant degree. The daily administration of 0.3 mg L-T4 to eight normal male volunteers for 1 month did not significantly affect HDL-C levels."}
{"id": "PMID:226560", "title": "Decreased high density lipoprotein cholesterol in hypopituitarism.", "content": "Serum triglyceride, cholesterol, and high density lipoprotein cholesterol (HDL-C) levels were measured in 10 men and 3 women with hypopituitarism. The mean total cholesterol and triglyceride levels were significantly increased but were within the range of controls. The mean HDL-C concentration and the HDL-C to total cholesterol ratio were significantly decreased. Similar findings were present in a patient with isolated GH deficiency. Two men with Kallman's syndrome and 3 patients with active acromegaly had values that were either within or just below the normal range. Replacement therapy with thyroid hormone and prednisone resulted in a normalization of HDL-C concentrations in four of the five patients studied. This improvement suggests a role for thyroid hormone and/or glucocorticoids in the maintenance of normal HDL-C concentrations. These observations also suggest that the distribution of plasma lipoprotein fractions is dependent in part, either directly or indirectly, on pituitary hormones.", "contents": "Decreased high density lipoprotein cholesterol in hypopituitarism. Serum triglyceride, cholesterol, and high density lipoprotein cholesterol (HDL-C) levels were measured in 10 men and 3 women with hypopituitarism. The mean total cholesterol and triglyceride levels were significantly increased but were within the range of controls. The mean HDL-C concentration and the HDL-C to total cholesterol ratio were significantly decreased. Similar findings were present in a patient with isolated GH deficiency. Two men with Kallman's syndrome and 3 patients with active acromegaly had values that were either within or just below the normal range. Replacement therapy with thyroid hormone and prednisone resulted in a normalization of HDL-C concentrations in four of the five patients studied. This improvement suggests a role for thyroid hormone and/or glucocorticoids in the maintenance of normal HDL-C concentrations. These observations also suggest that the distribution of plasma lipoprotein fractions is dependent in part, either directly or indirectly, on pituitary hormones."}
{"id": "PMID:226561", "title": "A syndrome of apparent mineralocorticoid excess associated with defects in the peripheral metabolism of cortisol.", "content": "A syndrome is described whose features, suggestive of primary mineralcorticoid excess, included hypertension, hypokalemia, low PRA, and responsiveness to spironolactone. Aldosterone levels were subnormal but as yet there has been no evidence of overproduction of other mineralocorticoids by chemical analysis or by bioassay of plasma and urinary extracts. The steroidal abnormalities that were observed involved peripheral matabolism rather than secretion. One patient exhibited a transient delay in reduction of the 3-keto group in the A ring, and both patients exhibited a decrease in the metabolism of cortisol to biologically inactive cortisone. This was shown by the marked decrease in the excretion of urinary metabolites bearing an 11-keto group and a decrease in the oxidation of 11 alpha-[3H]cortisol to tritiated water. The defect appeared not to be a deficiency of the 11 beta-oxidoreductase system itself, since the reverse reaction of conversion of cortisone to cortisol proceeded normally, but, rater, an alteration in the equilibrium position of 11 beta-oxidoreduction in favor of the reduced form. This was also expressed by a prolongation of the half-time of disappearance of cortisol. The decrease in the MCR permitted the maintenance of normal cortisol plasma levels and normal glucocorticoid function at a diminished rate of secretion. The decreased rate of conversion of cortisol to cortisone serves as a biochemical marker of this hypertensive syndrome.", "contents": "A syndrome of apparent mineralocorticoid excess associated with defects in the peripheral metabolism of cortisol. A syndrome is described whose features, suggestive of primary mineralcorticoid excess, included hypertension, hypokalemia, low PRA, and responsiveness to spironolactone. Aldosterone levels were subnormal but as yet there has been no evidence of overproduction of other mineralocorticoids by chemical analysis or by bioassay of plasma and urinary extracts. The steroidal abnormalities that were observed involved peripheral matabolism rather than secretion. One patient exhibited a transient delay in reduction of the 3-keto group in the A ring, and both patients exhibited a decrease in the metabolism of cortisol to biologically inactive cortisone. This was shown by the marked decrease in the excretion of urinary metabolites bearing an 11-keto group and a decrease in the oxidation of 11 alpha-[3H]cortisol to tritiated water. The defect appeared not to be a deficiency of the 11 beta-oxidoreductase system itself, since the reverse reaction of conversion of cortisone to cortisol proceeded normally, but, rater, an alteration in the equilibrium position of 11 beta-oxidoreduction in favor of the reduced form. This was also expressed by a prolongation of the half-time of disappearance of cortisol. The decrease in the MCR permitted the maintenance of normal cortisol plasma levels and normal glucocorticoid function at a diminished rate of secretion. The decreased rate of conversion of cortisol to cortisone serves as a biochemical marker of this hypertensive syndrome."}
{"id": "PMID:226562", "title": "Albright's osteodystrophy in a patient with renal hypercalciuria.", "content": "We have investigated an 18-yr-old hypercalciuric female with features of both renal hypercalciuria and pseudohypoparathyroidism. She had increased circulating parathyroid hormone levels, which are common to both diseases. She also had a modest hypocalcemia and low normal basal cAMP excretion, both of which are more likely to occur in pseudohypoparathyroidism. She also had Albright's osteodystrophy, which is frequent in patients with pseudohypoparathyroidism and has never been reported in patients with renal hypercalciuria. In contrast to patients with pseudohypoparathyroidism, her serum 1,25-dihydroxycholecalciferol level was increased and her renal responses to parathyroid hormone infusion, including renal calcium reabsorption, were normal. This patient, therefore, raises the possibility that some patients with renal hyperalciuria may have a forme fruste of pseudohypoparathyroidism.", "contents": "Albright's osteodystrophy in a patient with renal hypercalciuria. We have investigated an 18-yr-old hypercalciuric female with features of both renal hypercalciuria and pseudohypoparathyroidism. She had increased circulating parathyroid hormone levels, which are common to both diseases. She also had a modest hypocalcemia and low normal basal cAMP excretion, both of which are more likely to occur in pseudohypoparathyroidism. She also had Albright's osteodystrophy, which is frequent in patients with pseudohypoparathyroidism and has never been reported in patients with renal hypercalciuria. In contrast to patients with pseudohypoparathyroidism, her serum 1,25-dihydroxycholecalciferol level was increased and her renal responses to parathyroid hormone infusion, including renal calcium reabsorption, were normal. This patient, therefore, raises the possibility that some patients with renal hyperalciuria may have a forme fruste of pseudohypoparathyroidism."}
{"id": "PMID:226563", "title": "Cell-mediated and humoral immune responses to herpes simplex virus and cytomegalovirus in renal transplant patients.", "content": "Cell-mediated immunity to herpes simplex virus and cytomegalovirus, using the lymphocyte transformation test and interferon induction in lymphocytes, was studied in 59 patients from 1 day to 7 years after allotransplantation and compared with the results in normal subjects. Both parameters were permanently depressed with regard to cytomegalovirus. With herpes simplex virus, interferon production was also permanently depressed, whereas the transformation reaction was normal during the first year after transplantation and only slightly depressed in patients more than 1 year after transplantation. In 6 patients the above-mentioned assays and the complement fixation reaction were performed serially and related to the clinical signs of herpes simplex virus and cytomegalovirus infection. The relationship between depression of the transformation reaction and interferon production in lymphocytes and the occurrence of clinically evident herpes simplex virus and cytomegalovirus infections was, however, equivocal. The humoral immune response to herpes simplex virus was measured by the complement fixation test and the more sensitive antibody-dependent, cell-mediated cytotoxicity reaction, and a good correlation was found between these two tests, although only a few persons were found to be negative in the antibody-dependent, cell-mediated cytotoxicity reaction. The suggestion is made that only a few adults are \"true\" herpes simplex virus seronegative.", "contents": "Cell-mediated and humoral immune responses to herpes simplex virus and cytomegalovirus in renal transplant patients. Cell-mediated immunity to herpes simplex virus and cytomegalovirus, using the lymphocyte transformation test and interferon induction in lymphocytes, was studied in 59 patients from 1 day to 7 years after allotransplantation and compared with the results in normal subjects. Both parameters were permanently depressed with regard to cytomegalovirus. With herpes simplex virus, interferon production was also permanently depressed, whereas the transformation reaction was normal during the first year after transplantation and only slightly depressed in patients more than 1 year after transplantation. In 6 patients the above-mentioned assays and the complement fixation reaction were performed serially and related to the clinical signs of herpes simplex virus and cytomegalovirus infection. The relationship between depression of the transformation reaction and interferon production in lymphocytes and the occurrence of clinically evident herpes simplex virus and cytomegalovirus infections was, however, equivocal. The humoral immune response to herpes simplex virus was measured by the complement fixation test and the more sensitive antibody-dependent, cell-mediated cytotoxicity reaction, and a good correlation was found between these two tests, although only a few persons were found to be negative in the antibody-dependent, cell-mediated cytotoxicity reaction. The suggestion is made that only a few adults are \"true\" herpes simplex virus seronegative."}
{"id": "PMID:226564", "title": "Enzyme-linked fluorescence assay: Ultrasensitive solid-phase assay for detection of human rotavirus.", "content": "Enzyme-linked immunosorbent assay (ELISA) has proven to be a useful assay system for the direct detection of infectious agents. However, when the usual color-producing substrates are employed, relatively large amounts of substrate must be hydrolyzed by the bound enzyme before detection can be achieved. We attempted to improve the sensitivity of ELISA by utilizing a substrate that yields a fluorescent product on enzyme action. The enzyme-linked fluorescence assay (ELFA) based on this principle was approximately 100 times more sensitive than the corresponding ELISA or radioimmunoassay for the detection of human rotavirus in a standard stool suspension. In addition, the ELFA for human rotavirus was capable of detecting antigen in six specimens that were negative by ELISA. Five of these specimens were obtained late in the course of confirmed rotavirus infections. ELFA provides a simple, reliable, ultrasensitive method for the rapid detection of viral antigen.", "contents": "Enzyme-linked fluorescence assay: Ultrasensitive solid-phase assay for detection of human rotavirus. Enzyme-linked immunosorbent assay (ELISA) has proven to be a useful assay system for the direct detection of infectious agents. However, when the usual color-producing substrates are employed, relatively large amounts of substrate must be hydrolyzed by the bound enzyme before detection can be achieved. We attempted to improve the sensitivity of ELISA by utilizing a substrate that yields a fluorescent product on enzyme action. The enzyme-linked fluorescence assay (ELFA) based on this principle was approximately 100 times more sensitive than the corresponding ELISA or radioimmunoassay for the detection of human rotavirus in a standard stool suspension. In addition, the ELFA for human rotavirus was capable of detecting antigen in six specimens that were negative by ELISA. Five of these specimens were obtained late in the course of confirmed rotavirus infections. ELFA provides a simple, reliable, ultrasensitive method for the rapid detection of viral antigen."}
{"id": "PMID:226566", "title": "Efferent connections of the habenular nuclei in the rat.", "content": "The efferent connections of the medial (MHb) and lateral (LHb) habenular nuclei in the rat were demonstrated autoradiographically following small injections of tritiated amino acids localized within various parts of the habenular complex. Comparison of individual cases led to the following conclusions. MHb efferents form the core portion of the fasciculus retroflexus and pass to the interpeduncular nucleus (IP) in which they terminate in a topographic pattern that refects 90 degrees rotations such that dorsal MHb projects to lateral IP, medial MHb to ventral, and lateral MHb to dorsal IP. Most MHb fibers cross in the interpeduncular necleus in the \"figure 8\" pattern described by Cajal, and terminate throughout the width of IP with only moderate preference for the ipsilateral side. However, the most dorsal part of MHb projects almost exclusively to the most lateral IP zone in a cluster pattern that is particularly dense on the ipsilateral side. The MHb appears to have no other significant projections, but very sparse MHb fibers may pass to the supracommissural septum and to the median raphe nucleus. Except for some fibers passing ventrally into the mediodorsal nucleus, all of the LHb efferents enter the fasciculus retroflexus and compose the mantle portion of the bundle. No LHb projections follow the stria medullaris. In the ventral tegmental area LHb efferents become organized into groups that disperse in several directions: (a) Rostrally directed fibers follow the medial forebrain bundle to the lateral, posterior and dorsomedial hypothalamic nuclei, ventromedial thalamic nucleus, lateral preoptic area, substantia innominata and ventrolateral septum. (b) Fibers turning laterally distribute to the substantia nigra, pars compacta (SNC); a small number continue through SNC to adjacent tegmentum. (c) The largest contingent of LHb efferents passes dorsocaudally into paramedian midbrain regions including median and dorsal raphe nuclei, and to adjacent tegmental reticular formation. Sparse addition LHb projections pass to the pretectal area, superior colliculus, nucleus reticularis tegmenti pontis, parabrachial nuclei and locus coeruleus. No LHb projections appear to involve the interpeduncular nucleus. All of these connections are in varying degree bilateral, with decussations in the supramammillary region, ventral tegmental area and median raphe nucleus. On the basis of differential afferent and efferent connections, the LHb can be divided into a medial (M-LHb) and a lateral (L-LHb) portion. The M-LHb, receiving most of its afferents from limbic regions and only few from globus pallidus, projects mainly to the raphe nuclei, while L-LHb, afferented mainly by globus pallidus and in lesser degree by the limbic forebrain, projects predominantly to a large region of reticular formation alongside the median raphe nucleus. Both M-LHb and L-LHb, however, project to SNC. The reported data are discussed in correlation with recent histochemical findings.", "contents": "Efferent connections of the habenular nuclei in the rat. The efferent connections of the medial (MHb) and lateral (LHb) habenular nuclei in the rat were demonstrated autoradiographically following small injections of tritiated amino acids localized within various parts of the habenular complex. Comparison of individual cases led to the following conclusions. MHb efferents form the core portion of the fasciculus retroflexus and pass to the interpeduncular nucleus (IP) in which they terminate in a topographic pattern that refects 90 degrees rotations such that dorsal MHb projects to lateral IP, medial MHb to ventral, and lateral MHb to dorsal IP. Most MHb fibers cross in the interpeduncular necleus in the \"figure 8\" pattern described by Cajal, and terminate throughout the width of IP with only moderate preference for the ipsilateral side. However, the most dorsal part of MHb projects almost exclusively to the most lateral IP zone in a cluster pattern that is particularly dense on the ipsilateral side. The MHb appears to have no other significant projections, but very sparse MHb fibers may pass to the supracommissural septum and to the median raphe nucleus. Except for some fibers passing ventrally into the mediodorsal nucleus, all of the LHb efferents enter the fasciculus retroflexus and compose the mantle portion of the bundle. No LHb projections follow the stria medullaris. In the ventral tegmental area LHb efferents become organized into groups that disperse in several directions: (a) Rostrally directed fibers follow the medial forebrain bundle to the lateral, posterior and dorsomedial hypothalamic nuclei, ventromedial thalamic nucleus, lateral preoptic area, substantia innominata and ventrolateral septum. (b) Fibers turning laterally distribute to the substantia nigra, pars compacta (SNC); a small number continue through SNC to adjacent tegmentum. (c) The largest contingent of LHb efferents passes dorsocaudally into paramedian midbrain regions including median and dorsal raphe nuclei, and to adjacent tegmental reticular formation. Sparse addition LHb projections pass to the pretectal area, superior colliculus, nucleus reticularis tegmenti pontis, parabrachial nuclei and locus coeruleus. No LHb projections appear to involve the interpeduncular nucleus. All of these connections are in varying degree bilateral, with decussations in the supramammillary region, ventral tegmental area and median raphe nucleus. On the basis of differential afferent and efferent connections, the LHb can be divided into a medial (M-LHb) and a lateral (L-LHb) portion. The M-LHb, receiving most of its afferents from limbic regions and only few from globus pallidus, projects mainly to the raphe nuclei, while L-LHb, afferented mainly by globus pallidus and in lesser degree by the limbic forebrain, projects predominantly to a large region of reticular formation alongside the median raphe nucleus. Both M-LHb and L-LHb, however, project to SNC. The reported data are discussed in correlation with recent histochemical findings."}
{"id": "PMID:226567", "title": "The GABA neurons and their axon terminals in rat corpus striatum as demonstrated by GAD immunocytochemistry.", "content": "Glutamic acid decarboxylase (GAD, EC 4.1.1.15), the enzyme which catalyzes the alpha-decarboxylation of L-glutamate to form the neurotransmitter gamma-aminobutyric acid (GABA), was localized immunocytochemically in rat neostriatum, pallidum and entopeduncular nucleus. A large amount of GAD-positive reaction product was observed in both the pallidum and entopeduncular nucleus in light microscopic preparations and was localized ultrastructurally to axon terminalis that surrounded dendrites and large somata. In the neostriatum the relative numbers of GAD-positive axons terminals per unit area were substantially less than in the pallidum. GAD-positive terminals predominantly formed symmetric synapses with somata, dendrites and spines, but a small number of them formed asymmetric synapses with either dendrites or spines. The presence of GAD within these terminals is consistent with results of other investigations which have indicated that the striatopallidal and striatoentopeduncular pathways as well as neostriatal local circuit neurons and/or collaterals from neostriatal projection neurons, use GABA as a neurotransmitter. GAD-positive reaction product was also localized within the somata and dendrites of neostriatal and pallidal neurons in colchicine-injected preparations. The GAD-positive somata in the pallidum were medium-sized neurons and since such cells project to the substantia nigra, our results are in agreement with those from other studies which demonstrate a GABAergic, pallidonigral pathway. In the neostriatum, GAD-positive somata were identified light microscopically as medium-sized neurons with either round or fusiform shapes. Electron microscopic examinations also showed GAD-positive reaction product within the perikaryal and dendritic cytoplasm of these neurons, as well as in dendritic spines. These findings are in accord with the results of studies which have indicated that medium-sized, spinous neurons of the neostriatum give rise to a GABAergic, striatonigral pathway. The significance of GAD localization within these neostriatal neurons is discussed in relation to recent findings which show that substance P is contained within this same class of striatonigral projection neuron.", "contents": "The GABA neurons and their axon terminals in rat corpus striatum as demonstrated by GAD immunocytochemistry. Glutamic acid decarboxylase (GAD, EC 4.1.1.15), the enzyme which catalyzes the alpha-decarboxylation of L-glutamate to form the neurotransmitter gamma-aminobutyric acid (GABA), was localized immunocytochemically in rat neostriatum, pallidum and entopeduncular nucleus. A large amount of GAD-positive reaction product was observed in both the pallidum and entopeduncular nucleus in light microscopic preparations and was localized ultrastructurally to axon terminalis that surrounded dendrites and large somata. In the neostriatum the relative numbers of GAD-positive axons terminals per unit area were substantially less than in the pallidum. GAD-positive terminals predominantly formed symmetric synapses with somata, dendrites and spines, but a small number of them formed asymmetric synapses with either dendrites or spines. The presence of GAD within these terminals is consistent with results of other investigations which have indicated that the striatopallidal and striatoentopeduncular pathways as well as neostriatal local circuit neurons and/or collaterals from neostriatal projection neurons, use GABA as a neurotransmitter. GAD-positive reaction product was also localized within the somata and dendrites of neostriatal and pallidal neurons in colchicine-injected preparations. The GAD-positive somata in the pallidum were medium-sized neurons and since such cells project to the substantia nigra, our results are in agreement with those from other studies which demonstrate a GABAergic, pallidonigral pathway. In the neostriatum, GAD-positive somata were identified light microscopically as medium-sized neurons with either round or fusiform shapes. Electron microscopic examinations also showed GAD-positive reaction product within the perikaryal and dendritic cytoplasm of these neurons, as well as in dendritic spines. These findings are in accord with the results of studies which have indicated that medium-sized, spinous neurons of the neostriatum give rise to a GABAergic, striatonigral pathway. The significance of GAD localization within these neostriatal neurons is discussed in relation to recent findings which show that substance P is contained within this same class of striatonigral projection neuron."}
{"id": "PMID:226565", "title": "Effects of the beta-adrenoceptor blocking agent sotalol on CNS: sleep, EEG, and psychophysiological parameters.", "content": "Sotalol (Sotalex), 320 or 960 mg, was administered to 12 healthy subjects daily for a period of four days in a double-blind trial over 11 days. The effects of sotalol on heart rate, blood pressure, EEG, subjective quality of sleep, polygraphically determined sleep pattern, and psychophysiological parameters such as psychomotor performance, memory, perception, vigilance, and general condition were studied and were related to dosage and plasma levels. Steady-state plasma levels of sotalol were reached within 24 hours after a single dose; 960 mg resulted in plasma levels three times higher than those reached with 320 mg, which indicates first-order linear absorption. The effects of sotalol on EEG, sleep, and performance in psychological tests were equivocal and do not yield evidence for CNS activity of sotalol.", "contents": "Effects of the beta-adrenoceptor blocking agent sotalol on CNS: sleep, EEG, and psychophysiological parameters. Sotalol (Sotalex), 320 or 960 mg, was administered to 12 healthy subjects daily for a period of four days in a double-blind trial over 11 days. The effects of sotalol on heart rate, blood pressure, EEG, subjective quality of sleep, polygraphically determined sleep pattern, and psychophysiological parameters such as psychomotor performance, memory, perception, vigilance, and general condition were studied and were related to dosage and plasma levels. Steady-state plasma levels of sotalol were reached within 24 hours after a single dose; 960 mg resulted in plasma levels three times higher than those reached with 320 mg, which indicates first-order linear absorption. The effects of sotalol on EEG, sleep, and performance in psychological tests were equivocal and do not yield evidence for CNS activity of sotalol."}
{"id": "PMID:226570", "title": "Fluoride inhibition of polymorphonuclear leukocytes.", "content": "Significant inhibition of PMN metabolic activity by F- occurred at 0.1, 0.5 and 0.0 mM F- for O2- generation, 1-C14 CO2 release labeled glucose and NBT-reduction respectively. This inhibition resulted primarily from F- suppression of nonoxidative glucose metabolism. As the concentration of F- in the O2- generating system increased beyond 10 mM, a rise in production of O2- anion occurred, peaking at 20 mM F-, followed by a rapid decline.", "contents": "Fluoride inhibition of polymorphonuclear leukocytes. Significant inhibition of PMN metabolic activity by F- occurred at 0.1, 0.5 and 0.0 mM F- for O2- generation, 1-C14 CO2 release labeled glucose and NBT-reduction respectively. This inhibition resulted primarily from F- suppression of nonoxidative glucose metabolism. As the concentration of F- in the O2- generating system increased beyond 10 mM, a rise in production of O2- anion occurred, peaking at 20 mM F-, followed by a rapid decline."}
{"id": "PMID:226624", "title": "Isolation, identification and characterization of camelpox virus in Iraq.", "content": "A virus was isolated from pox-like lesions in camels during an outbreak of camelpox disease which occurred in December 1977 in an area near the Iraqi-Iranian border. It was identified serologically as a virus of the Orthopoxvirus group. The biological properties of the isolate indicated that it was probably identical with strains of camelpox virus isolated from Iran, Egypt, Kenya and the U.S.S.R.", "contents": "Isolation, identification and characterization of camelpox virus in Iraq. A virus was isolated from pox-like lesions in camels during an outbreak of camelpox disease which occurred in December 1977 in an area near the Iraqi-Iranian border. It was identified serologically as a virus of the Orthopoxvirus group. The biological properties of the isolate indicated that it was probably identical with strains of camelpox virus isolated from Iran, Egypt, Kenya and the U.S.S.R."}
{"id": "PMID:226576", "title": "Studies on the stability of rat testis membrane receptors for hLH, hCG and hFSH.", "content": "Receptor preparations from rat testes were stored at 4 C with various protease inhibitors and chemicals, at -20 C and -80 C, in freeze-dried form as well as at 4 C and 37 C after reconstitution in various media. Each preparation was tested for stability in terms of binding capacity of human luteinizing hormone (hLH), human chorionic gonadotropin (hCG) and human follicle-stimulating hormone (hFSH). The freeze-dried samples were stable for at least six months, although once reconstituted and stored at 4 C, they were less stable than fresh ones. Furthermore, Na azide and Na azide with diisopropylfluoro-phosphate (DIFP) prolonged the stability of the fresh samples. The samples stored at -20 C or -80 C were stable for at least 90 days and repeated freezing and thawing (15 times) did not change the binding capacity of either the hCG/hLH or hFSH receptors.", "contents": "Studies on the stability of rat testis membrane receptors for hLH, hCG and hFSH. Receptor preparations from rat testes were stored at 4 C with various protease inhibitors and chemicals, at -20 C and -80 C, in freeze-dried form as well as at 4 C and 37 C after reconstitution in various media. Each preparation was tested for stability in terms of binding capacity of human luteinizing hormone (hLH), human chorionic gonadotropin (hCG) and human follicle-stimulating hormone (hFSH). The freeze-dried samples were stable for at least six months, although once reconstituted and stored at 4 C, they were less stable than fresh ones. Furthermore, Na azide and Na azide with diisopropylfluoro-phosphate (DIFP) prolonged the stability of the fresh samples. The samples stored at -20 C or -80 C were stable for at least 90 days and repeated freezing and thawing (15 times) did not change the binding capacity of either the hCG/hLH or hFSH receptors."}
{"id": "PMID:226625", "title": "Tanapox. A serological survey of the lower Tana River Valley.", "content": "Sera collected from the indigenous population of the Tana River valley during the Tana River Expedition in 1976 were examined for neutralizing antibody to Tanapox virus. Antibody was found in 9.2% of the population in infected areas. This result and the presence of antibody in four children indicated that infection had continued to occur in the area since the 1962 outbreak.", "contents": "Tanapox. A serological survey of the lower Tana River Valley. Sera collected from the indigenous population of the Tana River valley during the Tana River Expedition in 1976 were examined for neutralizing antibody to Tanapox virus. Antibody was found in 9.2% of the population in infected areas. This result and the presence of antibody in four children indicated that infection had continued to occur in the area since the 1962 outbreak."}
{"id": "PMID:226577", "title": "Trypan Blue as a marker of plasma membrane permeability in alloxan-treated mouse islet cells.", "content": "Suspensions of pancreatic islet cells from noninbred ob/ob-mice were incubated with Trypan Blue. Microscope photometry showed that apparently viable cells excluded the dye completely, whereas the nuclei of nonviable cells accumulated Trypan Blue by a saturable process. The nucleus-to-medium dye gradient was more then 30:1 in media containing 0.1% or less Trypan Blue. The apparent affinity constant for nuclear binding of the dye was 3.1 X 10(4)l/mol. Albumin partially inhibited the nuclear staining. More than 0.5% Trypan Blue in the medium was toxic per se. In the absence of albumin, 0.5 or 20 mmol/l alloxan, 1 mmol/l N-ethylmaleimide, or 0.1 mmol/l chloromercuribenzene-p-sulphonic acid, but not 20 mmol/l streptozotocin, increased the frequency of islet cells stained with 0.1% Trypan Blue. The absorbance of nuceli was also increased in cells treated with alloxan or N-ethylmaleimide, but not in those treated with chloromercuribenze-p-sulphonic acid. It is concluded that alloxan rapidly increases the permeability of the plasma membrane in mouse beta-cells. This action of alloxan appears to be more acute than any such effect of streptozotocin.", "contents": "Trypan Blue as a marker of plasma membrane permeability in alloxan-treated mouse islet cells. Suspensions of pancreatic islet cells from noninbred ob/ob-mice were incubated with Trypan Blue. Microscope photometry showed that apparently viable cells excluded the dye completely, whereas the nuclei of nonviable cells accumulated Trypan Blue by a saturable process. The nucleus-to-medium dye gradient was more then 30:1 in media containing 0.1% or less Trypan Blue. The apparent affinity constant for nuclear binding of the dye was 3.1 X 10(4)l/mol. Albumin partially inhibited the nuclear staining. More than 0.5% Trypan Blue in the medium was toxic per se. In the absence of albumin, 0.5 or 20 mmol/l alloxan, 1 mmol/l N-ethylmaleimide, or 0.1 mmol/l chloromercuribenzene-p-sulphonic acid, but not 20 mmol/l streptozotocin, increased the frequency of islet cells stained with 0.1% Trypan Blue. The absorbance of nuceli was also increased in cells treated with alloxan or N-ethylmaleimide, but not in those treated with chloromercuribenze-p-sulphonic acid. It is concluded that alloxan rapidly increases the permeability of the plasma membrane in mouse beta-cells. This action of alloxan appears to be more acute than any such effect of streptozotocin."}
{"id": "PMID:226626", "title": "In vivo and in vitro studies on temperature-sensitive mutants of swine vesicular disease virus.", "content": "Two temperature-sensitive mutants of the Ukg 27/72 strain of swine vesicular disease virus were isolated in tissue culture and a third was derived following adaptation in mice. All three were found to have similar growth restrictive temperatures, but varied considerably in their virulence when administered to pigs. The route of inoculation appeared to exert a considerable influence on the apparent degree of attenuation, the antibody titre engendered and the transmission of disease to pigs held in contact with inoculated animals. One strain appeared almost totally attenuated when inoculated animals. One strain appeared almost totally attenuated when inoculated into pigs but spread to animals in contact causing severe disease. Virus re-isolated from one such animal was found to have retained its temperature sensitive phenotype, suggesting that virulence in this case was not directly related to temperature sensitivity. Pigs with high antibody titres were found to be susceptible when placed in contact with challenge animals, although the lesions which developed were mild.", "contents": "In vivo and in vitro studies on temperature-sensitive mutants of swine vesicular disease virus. Two temperature-sensitive mutants of the Ukg 27/72 strain of swine vesicular disease virus were isolated in tissue culture and a third was derived following adaptation in mice. All three were found to have similar growth restrictive temperatures, but varied considerably in their virulence when administered to pigs. The route of inoculation appeared to exert a considerable influence on the apparent degree of attenuation, the antibody titre engendered and the transmission of disease to pigs held in contact with inoculated animals. One strain appeared almost totally attenuated when inoculated animals. One strain appeared almost totally attenuated when inoculated into pigs but spread to animals in contact causing severe disease. Virus re-isolated from one such animal was found to have retained its temperature sensitive phenotype, suggesting that virulence in this case was not directly related to temperature sensitivity. Pigs with high antibody titres were found to be susceptible when placed in contact with challenge animals, although the lesions which developed were mild."}
{"id": "PMID:226628", "title": "Inhibition of the in vitro outgrowth of Epstein-Barr virus-infected lymphocytes by TG lymphocytes.", "content": "Human T lymphocytes subpopulations from subjects not acutely infected with EBV have been selected and examined for ability to inhibit the outgrowth of autologous B lymphocytes that have undergone in vitro infection with EB virus. The results show that only TG lymphocytes are inhibitory. TG lymphocytes from subjects who are EBV antibody-negative inhibit as well as those from subjects who have EBV antibody. TG lymphocyte populations, as well as other T cell fractions obtained from neonatal subjects, fail to inhibit the outgrowth of infected, autologous lymphocytes under the conditions tested. We propose that NK cells are responsible for the inhibitory effects described in this report.", "contents": "Inhibition of the in vitro outgrowth of Epstein-Barr virus-infected lymphocytes by TG lymphocytes. Human T lymphocytes subpopulations from subjects not acutely infected with EBV have been selected and examined for ability to inhibit the outgrowth of autologous B lymphocytes that have undergone in vitro infection with EB virus. The results show that only TG lymphocytes are inhibitory. TG lymphocytes from subjects who are EBV antibody-negative inhibit as well as those from subjects who have EBV antibody. TG lymphocyte populations, as well as other T cell fractions obtained from neonatal subjects, fail to inhibit the outgrowth of infected, autologous lymphocytes under the conditions tested. We propose that NK cells are responsible for the inhibitory effects described in this report."}
{"id": "PMID:226631", "title": "Chemotactic factor-induced generation of superoxide radicals by human neutrophils: evidence for the role of sodium.", "content": "The role of sodium ion in superoxide (O2-) generation by human peripheral neutrophils was investigated. Cells were activated by exposure to the synthetic tripeptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP), and O2- release was assessed by ferricytochrome c reduction after 5 min of incubation at 37 degrees C in the presence of FMLP 4 X 10(-8) M. In the absence of monovalent cations (isotonic glucose), negligible O2- generation occurred. There was a progressive increase in the magnitude of FMLP-induced O2- generation with increasing Na+ concentration up to 90 mM, where the response was noted to plateau. Varying the K+ concentration (1 to 10 mM) had no effect on the amount of O2- produced in the presence of Na+ 140 mM. FMLP also stimulated 22Na+ and 48Ca2+ uptake by the cells in a dose- and time-dependent fashion. FMLP-induced 22Na+ uptake appeared to be independent of the external Ca2+ concentration ( to 4 mM). In contrast, there was a progressive decrease in themagnitude of the FMLP-induced increase in 45Ca2+ uptake as the Na+ concentration was reduced by replacement with choline+ or glucose. These studies support a requirement for Na+ in FMLP-induced O2- generation and suggest that a Na+ influx may underlie the nature of this requirement. The data are also consistent with the hypothesis that a Na+ influx may precede the Ca2+ influx in the FMLP-induced activation sequence.", "contents": "Chemotactic factor-induced generation of superoxide radicals by human neutrophils: evidence for the role of sodium. The role of sodium ion in superoxide (O2-) generation by human peripheral neutrophils was investigated. Cells were activated by exposure to the synthetic tripeptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP), and O2- release was assessed by ferricytochrome c reduction after 5 min of incubation at 37 degrees C in the presence of FMLP 4 X 10(-8) M. In the absence of monovalent cations (isotonic glucose), negligible O2- generation occurred. There was a progressive increase in the magnitude of FMLP-induced O2- generation with increasing Na+ concentration up to 90 mM, where the response was noted to plateau. Varying the K+ concentration (1 to 10 mM) had no effect on the amount of O2- produced in the presence of Na+ 140 mM. FMLP also stimulated 22Na+ and 48Ca2+ uptake by the cells in a dose- and time-dependent fashion. FMLP-induced 22Na+ uptake appeared to be independent of the external Ca2+ concentration ( to 4 mM). In contrast, there was a progressive decrease in themagnitude of the FMLP-induced increase in 45Ca2+ uptake as the Na+ concentration was reduced by replacement with choline+ or glucose. These studies support a requirement for Na+ in FMLP-induced O2- generation and suggest that a Na+ influx may underlie the nature of this requirement. The data are also consistent with the hypothesis that a Na+ influx may precede the Ca2+ influx in the FMLP-induced activation sequence."}
{"id": "PMID:226632", "title": "Purification of human T and B cells by a discontinuous density gradient of percoll.", "content": "A simple technique for isolating human peripheral B and T cells is described. This method is based on the different mobility of cells in a discontinuous density gradient of Percoll. A population with a mean of 72.8% of surface stable Ig (B cells) is found in the top layer (fraction I) whereas T cells with less than 3% of Ig are distributed in the two lower layers (fractions II and III). B cells obtained by this method were highly viable and reacted strongly with anti-DRw specific sera, whereas T cells did not respond. The clear-cut difference between positive and negative reactions makes this technique very suitable for DRw typing. The proliferative response to PHA is decreased in fractions I and III while greatly increased in fraction II. The different mitogenic responses in the two fractions containing T cells probably represent two functionally distinct T cell subsets. Cells from all fractions are less activated than unseparated cells when Con A and PWM are used as mitogen. The technique is very rapid, avoids the interaction of cells with their specific receptors and gives both T and B cells in one step, all advantages over other methods commonly used.", "contents": "Purification of human T and B cells by a discontinuous density gradient of percoll. A simple technique for isolating human peripheral B and T cells is described. This method is based on the different mobility of cells in a discontinuous density gradient of Percoll. A population with a mean of 72.8% of surface stable Ig (B cells) is found in the top layer (fraction I) whereas T cells with less than 3% of Ig are distributed in the two lower layers (fractions II and III). B cells obtained by this method were highly viable and reacted strongly with anti-DRw specific sera, whereas T cells did not respond. The clear-cut difference between positive and negative reactions makes this technique very suitable for DRw typing. The proliferative response to PHA is decreased in fractions I and III while greatly increased in fraction II. The different mitogenic responses in the two fractions containing T cells probably represent two functionally distinct T cell subsets. Cells from all fractions are less activated than unseparated cells when Con A and PWM are used as mitogen. The technique is very rapid, avoids the interaction of cells with their specific receptors and gives both T and B cells in one step, all advantages over other methods commonly used."}
{"id": "PMID:226636", "title": "Primary oat cell carcinoma of the larynx.", "content": "A case of primary oat cell carcinoma of the larynx in a forty-year-old female has been described. The tumour is rare and extremely aggressive. Surgical treatment and irradiation appear to halt the disease for a short time.", "contents": "Primary oat cell carcinoma of the larynx. A case of primary oat cell carcinoma of the larynx in a forty-year-old female has been described. The tumour is rare and extremely aggressive. Surgical treatment and irradiation appear to halt the disease for a short time."}
{"id": "PMID:226637", "title": "Apolipoprotein B: its role in the control of fibroblast cholesterol biosynthesis and in the regulation of its own binding to cellular receptors.", "content": "Apolipoprotein B transports cholesterol in plasma as low density lipoprotein (LDL) and targets its delivery to cells by binding to a specific plasma membrane receptor. The cellular consequences of apoB binding to its receptor were investigated to determine whether it suppresses cholesterol biosynthesis and reduces the number of cellular receptors for the apoprotein. Upon preincubation of fibroblasts with lipoprotein-deficient medium alone or supplemented with either LDL or apoB complexed to BSA (apoB-BSA), LDL suppressed cholesterol biosynthesis, but apoB enhanced it. Similarly, fibroblasts preincubated in medium supplemented with LDL bound decreased amounts of either (125)I-labeled LDL or (125)I-labeled apoB-BSA to their receptors, while preincubation with apoB-BSA increased the binding relative to the controls. These latter results occurred in association with a decrease in cellular cholesterol content, indicating that apoB in the medium bound cholesterol and removed it from the cells, thus stimulating both cholesterol synthesis and cellular binding of apoB. Accordingly, fibroblast cholesterol synthesis and the number of functional LDL receptors are not suppressed by the binding of the apoprotein to the receptor, and the known role of apoB remains that of transporting cholesterol in plasma and delivering it to the cell. A possible physiologic role for apoB in depleting cells of cholesterol is presently unknown since apoB is not known to exist free in plasma; however, these findings demonstrate such a functional capability for this apoprotein.-Shireman, R. B., and W. R. Fisher. Apolipoprotein B: its role in the control of fibroblast cholesterol biosynthesis and in the regulation of its own binding to cellular receptors.", "contents": "Apolipoprotein B: its role in the control of fibroblast cholesterol biosynthesis and in the regulation of its own binding to cellular receptors. Apolipoprotein B transports cholesterol in plasma as low density lipoprotein (LDL) and targets its delivery to cells by binding to a specific plasma membrane receptor. The cellular consequences of apoB binding to its receptor were investigated to determine whether it suppresses cholesterol biosynthesis and reduces the number of cellular receptors for the apoprotein. Upon preincubation of fibroblasts with lipoprotein-deficient medium alone or supplemented with either LDL or apoB complexed to BSA (apoB-BSA), LDL suppressed cholesterol biosynthesis, but apoB enhanced it. Similarly, fibroblasts preincubated in medium supplemented with LDL bound decreased amounts of either (125)I-labeled LDL or (125)I-labeled apoB-BSA to their receptors, while preincubation with apoB-BSA increased the binding relative to the controls. These latter results occurred in association with a decrease in cellular cholesterol content, indicating that apoB in the medium bound cholesterol and removed it from the cells, thus stimulating both cholesterol synthesis and cellular binding of apoB. Accordingly, fibroblast cholesterol synthesis and the number of functional LDL receptors are not suppressed by the binding of the apoprotein to the receptor, and the known role of apoB remains that of transporting cholesterol in plasma and delivering it to the cell. A possible physiologic role for apoB in depleting cells of cholesterol is presently unknown since apoB is not known to exist free in plasma; however, these findings demonstrate such a functional capability for this apoprotein.-Shireman, R. B., and W. R. Fisher. Apolipoprotein B: its role in the control of fibroblast cholesterol biosynthesis and in the regulation of its own binding to cellular receptors."}
{"id": "PMID:226638", "title": "Very low density lipoprotein. Fate of phospholipids, cholesterol, and apolipoprotein C during lipolysis in vitro.", "content": "In this study we have determined the fate of phospholipids, cholesterol, and apolipoprotein C during lipolysis of rat plasma very low density lipoprotein (rat VLDL). The experiment was carried out in vitro with lipoprotein lipase purified from bovine milk, VLDL labeled with [(14)C]palmitate, [(3)H]cholesterol, [(32)P]phospholipids, and (125)I-labeled apolipoprotein C and in plasma-devoid systems. Triglyceride hydrolysis ranged between 0 and 98.6%. [(32)P]Phospholipids, unesterified [(3)H]cholesterol, and (125)I-labeled apolipoprotein C were removed from the VLDL (d < 1.019 g/ml) during lipolysis. About one-third of the [(32)P]phosphatidylcholine was hydrolyzed to lysolecithin, and was transferred to the fraction d > 1.21 g/ml. The other two-thirds of the phospholipids were removed unhydrolyzed, mainly to the fraction d 1.04-1.21 g/ml. With the progression of the lipolysis, unesterified [(3)H]cholesterol was removed from VLDL at increasing rates, predominantly to the fraction d 1.04-1.21 g/ml. (125)I-Labeled apolipoprotein C removed from the VLDL partitioned between the fraction of d 1.04-1.21 g/ml and d > 1.21 g/ml. Negative-staining electron microscopy of the fraction d 1.04-1.21 g/ml (containing phospholipids, unesterified cholesterol, and apolipoprotein C) revealed many discoidal lipoproteins. [(3)H]Cholesteryl esters remained associated with the VLDL even when 70-80% of the triglycerides were hydrolyzed. These observations suggest that during in vitro lipolysis of VLDL, surface constituents leave the lipoprotein concomitantly with the hydrolysis of core triglycerides. The process of removal of surface constituents is independent of the presence of an acceptor lipoprotein and may occur in the form of a surface-fragment particle. -Eisenberg, S., and T. Olivecrona. Very low density lipoprotein. Fate of phospholipids, cholesterol, and apolipoprotein C during lipolysis in vitro.", "contents": "Very low density lipoprotein. Fate of phospholipids, cholesterol, and apolipoprotein C during lipolysis in vitro. In this study we have determined the fate of phospholipids, cholesterol, and apolipoprotein C during lipolysis of rat plasma very low density lipoprotein (rat VLDL). The experiment was carried out in vitro with lipoprotein lipase purified from bovine milk, VLDL labeled with [(14)C]palmitate, [(3)H]cholesterol, [(32)P]phospholipids, and (125)I-labeled apolipoprotein C and in plasma-devoid systems. Triglyceride hydrolysis ranged between 0 and 98.6%. [(32)P]Phospholipids, unesterified [(3)H]cholesterol, and (125)I-labeled apolipoprotein C were removed from the VLDL (d < 1.019 g/ml) during lipolysis. About one-third of the [(32)P]phosphatidylcholine was hydrolyzed to lysolecithin, and was transferred to the fraction d > 1.21 g/ml. The other two-thirds of the phospholipids were removed unhydrolyzed, mainly to the fraction d 1.04-1.21 g/ml. With the progression of the lipolysis, unesterified [(3)H]cholesterol was removed from VLDL at increasing rates, predominantly to the fraction d 1.04-1.21 g/ml. (125)I-Labeled apolipoprotein C removed from the VLDL partitioned between the fraction of d 1.04-1.21 g/ml and d > 1.21 g/ml. Negative-staining electron microscopy of the fraction d 1.04-1.21 g/ml (containing phospholipids, unesterified cholesterol, and apolipoprotein C) revealed many discoidal lipoproteins. [(3)H]Cholesteryl esters remained associated with the VLDL even when 70-80% of the triglycerides were hydrolyzed. These observations suggest that during in vitro lipolysis of VLDL, surface constituents leave the lipoprotein concomitantly with the hydrolysis of core triglycerides. The process of removal of surface constituents is independent of the presence of an acceptor lipoprotein and may occur in the form of a surface-fragment particle. -Eisenberg, S., and T. Olivecrona. Very low density lipoprotein. Fate of phospholipids, cholesterol, and apolipoprotein C during lipolysis in vitro."}
{"id": "PMID:226639", "title": "Preparation and properties of soluble, immunoreactive apoLDL.", "content": "Immunoreactive apo-low density lipoprotein (LDL), soluble in mildly alkaline buffers of low ionic strength, was prepared by attaching LDL to a DEAE-Sepharose column and eluting the lipids with a 0--2% (w/v) gradient of nonionic detergents. Brij-36T, Nonidet P-40, and Triton X-100 gave similar results. After washing the detergent from the column, the bound apoLDL was eluted with 1 M NaCl, pH 7.4, with recoveries up to 85%. This apoLDL could be dialyzed extensively against low ionic strength solutions, and remained soluble as long as the pH was above 7. Spectrophotometric analysis showed that less than 0.1% %w/v) of cholesterol or phospholipids and less than 1% (w/v) of detergent remained associated with the protein. The apoLDL cross-reacted with LDL against antisera prepared vs. intact LDL. Pore-gradient polyacrylamide gel electrophoresis, with SDS and urea, showed that this preparation was less aggregated than organic solvent extracted apolLDL and appeared to be made of oligomers of two monomeric subunits, one with molecular weight around 22,700 and a smaller one of approximately 8000. Isoelectric focusing showed that there also was charge heterogeneity in the soluble apoLDL.", "contents": "Preparation and properties of soluble, immunoreactive apoLDL. Immunoreactive apo-low density lipoprotein (LDL), soluble in mildly alkaline buffers of low ionic strength, was prepared by attaching LDL to a DEAE-Sepharose column and eluting the lipids with a 0--2% (w/v) gradient of nonionic detergents. Brij-36T, Nonidet P-40, and Triton X-100 gave similar results. After washing the detergent from the column, the bound apoLDL was eluted with 1 M NaCl, pH 7.4, with recoveries up to 85%. This apoLDL could be dialyzed extensively against low ionic strength solutions, and remained soluble as long as the pH was above 7. Spectrophotometric analysis showed that less than 0.1% %w/v) of cholesterol or phospholipids and less than 1% (w/v) of detergent remained associated with the protein. The apoLDL cross-reacted with LDL against antisera prepared vs. intact LDL. Pore-gradient polyacrylamide gel electrophoresis, with SDS and urea, showed that this preparation was less aggregated than organic solvent extracted apolLDL and appeared to be made of oligomers of two monomeric subunits, one with molecular weight around 22,700 and a smaller one of approximately 8000. Isoelectric focusing showed that there also was charge heterogeneity in the soluble apoLDL."}
{"id": "PMID:226640", "title": "Determination of mevalonate in blood plasma in man and rat. Mevalonate \"tolerance\" tests in man.", "content": "A method is described for the determination of mevalonate in ultrafiltrates of blood plasma. The method depends on the phosphorylation of mevalonate with [gamma-32P]ATP and mevalonate kinase to 5-[32P]phosphomevalonate, and the subsequent isolation of the 5-[32P]phosphomevalonate together with known amounts of added 5-phospho[14C]mevalonate by ion-exchange chromatography. The 32P/14C ratio in the isolated 5-phosphomevalonate is a linear function of the mevalonate content of the samples. The smallest amount that can be determined is 1--2 pmol. The fasting level in human plasma varied between 20 and 75 pmol/ml. Human red blood cells absorb mevalonate from plasma relatively slowly; their maximum storage capacity is about 1.3 pmol/10(6) red cells. An oral and intravenous \"mevalonate tolerance test\" in man is described that can be carried out with 200 and 30 mumol. respectively, of the unlabeled (RS)-mevalonate in a 70-kg man. Beer and wine contain mevalonate at a concentration of  3--8 microns, too low to provide a significant amount of mevalonate even for heavy drinkers. The mevalonate content of the plasma from the blood of the vena cava inferior of male rats varied between 81 and 502 pmol/ml and is positively related to the levels of liver 3-hydroxy-3-methylgultaryl-CoA reductase, suggesting that the liver is probably the main source of mevalonate circulating in blood. The plasma of renal venous blood contained only 33--85% as much mevalonate as the arterial plasma.", "contents": "Determination of mevalonate in blood plasma in man and rat. Mevalonate \"tolerance\" tests in man. A method is described for the determination of mevalonate in ultrafiltrates of blood plasma. The method depends on the phosphorylation of mevalonate with [gamma-32P]ATP and mevalonate kinase to 5-[32P]phosphomevalonate, and the subsequent isolation of the 5-[32P]phosphomevalonate together with known amounts of added 5-phospho[14C]mevalonate by ion-exchange chromatography. The 32P/14C ratio in the isolated 5-phosphomevalonate is a linear function of the mevalonate content of the samples. The smallest amount that can be determined is 1--2 pmol. The fasting level in human plasma varied between 20 and 75 pmol/ml. Human red blood cells absorb mevalonate from plasma relatively slowly; their maximum storage capacity is about 1.3 pmol/10(6) red cells. An oral and intravenous \"mevalonate tolerance test\" in man is described that can be carried out with 200 and 30 mumol. respectively, of the unlabeled (RS)-mevalonate in a 70-kg man. Beer and wine contain mevalonate at a concentration of  3--8 microns, too low to provide a significant amount of mevalonate even for heavy drinkers. The mevalonate content of the plasma from the blood of the vena cava inferior of male rats varied between 81 and 502 pmol/ml and is positively related to the levels of liver 3-hydroxy-3-methylgultaryl-CoA reductase, suggesting that the liver is probably the main source of mevalonate circulating in blood. The plasma of renal venous blood contained only 33--85% as much mevalonate as the arterial plasma."}
{"id": "PMID:226641", "title": "Lipids of whole cells and plasma membrane fractions from Balb/c3T3, SV3T3, and concanavalin A-selected revertant cells.", "content": "The lipid composition of Balb/c3T3, SV3T3, and the concanavalin A-selected SV3T3 revertant cells has been analyzed at the whole cell and plasma membrane levels. In comparison to untransformed 3T3 whole cells, SV3T3 cells showed an unchanged content of triacylglycerols, free fatty acids, and glycerylether diesters but a lower concentration of total phospholipids, while no significant difference was found in the phospholipid composition. Whole SV3T3 revertant cells exhibited a lipid composition similar to that in untransformed 3T3 cells with the exception of a higher proportion of sphingomyelin. Analysis of isolated plasma membranes did not reveal any significant differences in the cholesterol to phospholipid molar ratio between 3T3 and SV3T3 or SV3T3 revertant cells. The major changes in the acyl chain pattern SV3T3 compared with whole 3T3 cells consisted of an increase of oleic and palmitoleic acids coupled with a decrease of C20 and C22 polyunsaturated acids in phosphatidylethanolamine and phosphatidylcholine; an increase of oleic acid was also evident in SV3T3 phosphatidylinositol plus phosphatidylserine. An increase of palmitoleic and oleic acids together with a decrease of arachidonic acid was also found in phosphatidylethanolamine of SV3T3 plasma membranes; the only change in SV3T3 plasma membrane phosphatidylcholine was an increase of oleic acid. An increase of monoenoic acids together with a decrease of arachidonic acid was also found in phosphatidylethanolamine, phosphatidylcholine, and phosphatidylinositol plus phosphatidylserine of SV3T3 revertant cells at the level of both whole cells and plasma membranes.", "contents": "Lipids of whole cells and plasma membrane fractions from Balb/c3T3, SV3T3, and concanavalin A-selected revertant cells. The lipid composition of Balb/c3T3, SV3T3, and the concanavalin A-selected SV3T3 revertant cells has been analyzed at the whole cell and plasma membrane levels. In comparison to untransformed 3T3 whole cells, SV3T3 cells showed an unchanged content of triacylglycerols, free fatty acids, and glycerylether diesters but a lower concentration of total phospholipids, while no significant difference was found in the phospholipid composition. Whole SV3T3 revertant cells exhibited a lipid composition similar to that in untransformed 3T3 cells with the exception of a higher proportion of sphingomyelin. Analysis of isolated plasma membranes did not reveal any significant differences in the cholesterol to phospholipid molar ratio between 3T3 and SV3T3 or SV3T3 revertant cells. The major changes in the acyl chain pattern SV3T3 compared with whole 3T3 cells consisted of an increase of oleic and palmitoleic acids coupled with a decrease of C20 and C22 polyunsaturated acids in phosphatidylethanolamine and phosphatidylcholine; an increase of oleic acid was also evident in SV3T3 phosphatidylinositol plus phosphatidylserine. An increase of palmitoleic and oleic acids together with a decrease of arachidonic acid was also found in phosphatidylethanolamine of SV3T3 plasma membranes; the only change in SV3T3 plasma membrane phosphatidylcholine was an increase of oleic acid. An increase of monoenoic acids together with a decrease of arachidonic acid was also found in phosphatidylethanolamine, phosphatidylcholine, and phosphatidylinositol plus phosphatidylserine of SV3T3 revertant cells at the level of both whole cells and plasma membranes."}
{"id": "PMID:226642", "title": "Apoproteins of high density lipoproteins in the urine of normal subjects.", "content": "Apoproteins of high density lipoproteins were detected in the urine of normal subjects after the urinary proteins were highly concentrated. By immunoelectrophoresis, all of the urinary apoproteins gave precipitin lines with similar electrophoretic mobility. This suggests that the various apoproteins are present in the same particle. The apoproteins were present only in the ultracentrifugal fraction of density greater than 1.24 g/ml. Neither apoprotein B nor apoprotein E were detected in the urine, suggesting that very low density and low density lipoproteins are not excreted in the urine of normal subjects.", "contents": "Apoproteins of high density lipoproteins in the urine of normal subjects. Apoproteins of high density lipoproteins were detected in the urine of normal subjects after the urinary proteins were highly concentrated. By immunoelectrophoresis, all of the urinary apoproteins gave precipitin lines with similar electrophoretic mobility. This suggests that the various apoproteins are present in the same particle. The apoproteins were present only in the ultracentrifugal fraction of density greater than 1.24 g/ml. Neither apoprotein B nor apoprotein E were detected in the urine, suggesting that very low density and low density lipoproteins are not excreted in the urine of normal subjects."}
{"id": "PMID:226643", "title": "Interaction of bovine serum high density lipoprotein with mixed vesicles of phosphatidylcholine and cholesterol.", "content": "The interaction of sonicated, small vesicles of egg phosphatidylcholine and cholesterol (2:1, mol/mol) with bovine high density serum lipoproteins was examined in terms of lipid transfer between both types of particles and the resulting changes in lipoprotein structure. Saturation of high density lipoprotein preparations with vesicle lipids gave final lipoprotein particles with essentially unchanged protein content and composition, unchanged cholesterylester and nonpolar lipid content, but with markedly increased phospholipid content (59% increas by weight) and moderately increased cholesterol content (20% increase by weight). The lipoproteins enriched in lipid were relatively uniform, spherical particles, 110 +/- 3.6 A in diameter (6 A larger than the original lipoproteins); they had a markedly decreased intrinsic protein fluorescence, a red-shifted fluorescence wavelength maximum, and more fluid lipid domains. These results indicate that the direct addition of excess lipids from membranes or other lipoproteins is a possible mechanism for lipid transfer to high density lipoproteins. Also they suggest a structural flexibility of high density lipoproteins that allows the addition of significant amounts of surface components.", "contents": "Interaction of bovine serum high density lipoprotein with mixed vesicles of phosphatidylcholine and cholesterol. The interaction of sonicated, small vesicles of egg phosphatidylcholine and cholesterol (2:1, mol/mol) with bovine high density serum lipoproteins was examined in terms of lipid transfer between both types of particles and the resulting changes in lipoprotein structure. Saturation of high density lipoprotein preparations with vesicle lipids gave final lipoprotein particles with essentially unchanged protein content and composition, unchanged cholesterylester and nonpolar lipid content, but with markedly increased phospholipid content (59% increas by weight) and moderately increased cholesterol content (20% increase by weight). The lipoproteins enriched in lipid were relatively uniform, spherical particles, 110 +/- 3.6 A in diameter (6 A larger than the original lipoproteins); they had a markedly decreased intrinsic protein fluorescence, a red-shifted fluorescence wavelength maximum, and more fluid lipid domains. These results indicate that the direct addition of excess lipids from membranes or other lipoproteins is a possible mechanism for lipid transfer to high density lipoproteins. Also they suggest a structural flexibility of high density lipoproteins that allows the addition of significant amounts of surface components."}
{"id": "PMID:226644", "title": "Aminopropyl silica gel as a solid support for preparation of glycolipid immunoadsorbent and purification of antibodies.", "content": "Aminopropyl silica gel was prepared from porous silica gel and was used as a solid support for immunoadsorbent in the purification of anti-glycolipid antibodies. For neutral glycosphingolipids, a carboxyl function was generated by oxidation of the olefinic double bond of the sphingosine moiety, whereas for gangliosides the carboxyl group of sialic acid was used to couple with aminopropyl silica gel in the presence of a carbodiimide. These compounds were used for purifying anti-glycolipid antibodies from serum of immunized rabbits. The antibodies bound to the su-strate were released by 2 M potassium thiocyanate and their immunological properties were studied. Aminopropyl silica gel may be preferred over conventional organic solid supports for the following reasons: 1) faster flow rate; 2) higher capacity; 3) easier handling; 4) more economical; and 5) lower susceptibility to microbial attack.", "contents": "Aminopropyl silica gel as a solid support for preparation of glycolipid immunoadsorbent and purification of antibodies. Aminopropyl silica gel was prepared from porous silica gel and was used as a solid support for immunoadsorbent in the purification of anti-glycolipid antibodies. For neutral glycosphingolipids, a carboxyl function was generated by oxidation of the olefinic double bond of the sphingosine moiety, whereas for gangliosides the carboxyl group of sialic acid was used to couple with aminopropyl silica gel in the presence of a carbodiimide. These compounds were used for purifying anti-glycolipid antibodies from serum of immunized rabbits. The antibodies bound to the su-strate were released by 2 M potassium thiocyanate and their immunological properties were studied. Aminopropyl silica gel may be preferred over conventional organic solid supports for the following reasons: 1) faster flow rate; 2) higher capacity; 3) easier handling; 4) more economical; and 5) lower susceptibility to microbial attack."}
{"id": "PMID:226648", "title": "Evaluation of the bovine testicular radioreceptor assay for pituitary follicle-stimulating hormone.", "content": "A modified bovine testicular receptor was used to evaluate highly purified follicle-stimulating hormone (FSH) from a number of species. The particulate receptor obtained from adult bovine testes could be stored frozen or lyophilized for long periods without appreciable decrease in the binding of the ligand facility or in loss of specificity. The bovine testis receptor binds twice as much 125I-labelled ovine FSH as 125I-labelled human hormone. When FSH from different species was compared against NIH-FSH-S10, using various FSH ligands, the ovine hormone was clearly the most active, although many had comparable in-vivo biological potencies. The results suggest that there is probably some species specificity in the hormone-receptor interactions. As the ovine hormone is structurally closer to the bovine, from which the receptor was derived, it appears to have the highest activity in vitro. Marked differences in the biological activities of the different preparations between the human chorionic gonadotrophin-augmentation test and the in-vitro assays have been observed. In the in-vitro assays, all preparations, with the exception of the porcine hormone preparation, were less active and the ratio of bioassay/radioreceptor assay varied widely. In the radioreceptor assays, all FSH preparations except pregnant mare serum gonadotrophin (PMSG) showed parallel inhibition curves. The three different PMSG preparations examined gave inhibition lines that were parallel to each other.", "contents": "Evaluation of the bovine testicular radioreceptor assay for pituitary follicle-stimulating hormone. A modified bovine testicular receptor was used to evaluate highly purified follicle-stimulating hormone (FSH) from a number of species. The particulate receptor obtained from adult bovine testes could be stored frozen or lyophilized for long periods without appreciable decrease in the binding of the ligand facility or in loss of specificity. The bovine testis receptor binds twice as much 125I-labelled ovine FSH as 125I-labelled human hormone. When FSH from different species was compared against NIH-FSH-S10, using various FSH ligands, the ovine hormone was clearly the most active, although many had comparable in-vivo biological potencies. The results suggest that there is probably some species specificity in the hormone-receptor interactions. As the ovine hormone is structurally closer to the bovine, from which the receptor was derived, it appears to have the highest activity in vitro. Marked differences in the biological activities of the different preparations between the human chorionic gonadotrophin-augmentation test and the in-vitro assays have been observed. In the in-vitro assays, all preparations, with the exception of the porcine hormone preparation, were less active and the ratio of bioassay/radioreceptor assay varied widely. In the radioreceptor assays, all FSH preparations except pregnant mare serum gonadotrophin (PMSG) showed parallel inhibition curves. The three different PMSG preparations examined gave inhibition lines that were parallel to each other."}
{"id": "PMID:226649", "title": "Effects of prostaglandin E2 and dibutyryl cyclic AMP on the histamine-induced production of cortisol and corticosterone in isolated canine adrenal cells.", "content": "The steroidogenic effect of histamine in isolated adrenocortical cells of the dog was investigated in the presence of prostaglandin E2 (PGE2) and/or dibutyryl cyclic AMP (dbcAMP) in the medium. The effect of histamine, in combination with PGE2 was less than their total individual effects in the production of cortisol, but not ofcorticosterone. With dbcAMP the effect was just equal to them. However, the combination of histamine, PGE2 and dbcAMP showed an increase twice that of their total individual effects in the production of both steroids. These results indicate that, in the dog, histamine, PGE2 and dbcAMP may act synergistically in the adrenocortical cells.", "contents": "Effects of prostaglandin E2 and dibutyryl cyclic AMP on the histamine-induced production of cortisol and corticosterone in isolated canine adrenal cells. The steroidogenic effect of histamine in isolated adrenocortical cells of the dog was investigated in the presence of prostaglandin E2 (PGE2) and/or dibutyryl cyclic AMP (dbcAMP) in the medium. The effect of histamine, in combination with PGE2 was less than their total individual effects in the production of cortisol, but not ofcorticosterone. With dbcAMP the effect was just equal to them. However, the combination of histamine, PGE2 and dbcAMP showed an increase twice that of their total individual effects in the production of both steroids. These results indicate that, in the dog, histamine, PGE2 and dbcAMP may act synergistically in the adrenocortical cells."}
{"id": "PMID:226650", "title": "Intestinal parasites in Laotian refugees.", "content": "Laotian refugees relocated in the Columbus, Ohio, area were screened for intestinal parasites. Eight different pathogens were isolated. The prevalence of the various organisms ranged from 4 to 61 percent of persons affected and 18 to 100 percent of families. These data show a higher prevalence of parasitic disease than that revealed by previous observations by the Center for Disease Control among Southeast Asian refugees. It was also apparent that neither federal nor local programs were adequate to meet the special health care needs of these refugees nor to safeguard the health of communities they entered.", "contents": "Intestinal parasites in Laotian refugees. Laotian refugees relocated in the Columbus, Ohio, area were screened for intestinal parasites. Eight different pathogens were isolated. The prevalence of the various organisms ranged from 4 to 61 percent of persons affected and 18 to 100 percent of families. These data show a higher prevalence of parasitic disease than that revealed by previous observations by the Center for Disease Control among Southeast Asian refugees. It was also apparent that neither federal nor local programs were adequate to meet the special health care needs of these refugees nor to safeguard the health of communities they entered."}
{"id": "PMID:226655", "title": "Cell-mediated immunity to cytomegalovirus in patients receiving immunosuppressive therapy.", "content": "Employing the techniques of complement-fixation (CF), immunofluorescence (IF), and in vitro lymphocyte transformation (LTF), the humoral antibody response and cell-mediated immune (CMI) response to cytomegalovirus (CMV) were studied in the serum and peripheral blood lymphocytes in 19 normal children (controls) and 23 patients with renal disease who were receiving immunosuppressive therapy or undergoing hemodialysis. The LTF activity was determined by the whole blood microassay using two strains of CMV (AD-169 and Davis) and phytohemagglutinin (PHA). The antibody level responses to CMV in different groups of subjects were generally similar. The LTF response to PHA as evidenced by delta cpm activity was moderately depressed in immunosuppressed and hemodialyzed subjects compared to the response observed in the controls. The mean delta cpm activities in response to AD-169 and Davis strains of CMV in seropositive immunosuppressed patients were about one-fifth and one-third lower respectively than those of seropositive normal controls. These observations suggest that an impairment of CMV specific cellular immunity may be an important mechanism underlying the increased susceptibility to CMV infections in patients with chronic renal disease who receive immunosuppressive therapy.", "contents": "Cell-mediated immunity to cytomegalovirus in patients receiving immunosuppressive therapy. Employing the techniques of complement-fixation (CF), immunofluorescence (IF), and in vitro lymphocyte transformation (LTF), the humoral antibody response and cell-mediated immune (CMI) response to cytomegalovirus (CMV) were studied in the serum and peripheral blood lymphocytes in 19 normal children (controls) and 23 patients with renal disease who were receiving immunosuppressive therapy or undergoing hemodialysis. The LTF activity was determined by the whole blood microassay using two strains of CMV (AD-169 and Davis) and phytohemagglutinin (PHA). The antibody level responses to CMV in different groups of subjects were generally similar. The LTF response to PHA as evidenced by delta cpm activity was moderately depressed in immunosuppressed and hemodialyzed subjects compared to the response observed in the controls. The mean delta cpm activities in response to AD-169 and Davis strains of CMV in seropositive immunosuppressed patients were about one-fifth and one-third lower respectively than those of seropositive normal controls. These observations suggest that an impairment of CMV specific cellular immunity may be an important mechanism underlying the increased susceptibility to CMV infections in patients with chronic renal disease who receive immunosuppressive therapy."}
{"id": "PMID:226656", "title": "Human rotavirus in an adult population with travelers' diarrhea and its relationship to the location of food consumption.", "content": "The role of human rotavirus in adult diarrhea was evaluated in 164 newly arrived US students attending summer school at an urban Mexican university. Rotavirus was identified in stool samples by electron microscopy. Rotavirus was found in 26 of 109 students with diarrhea (24%) and in 8 of 55 asymptomatic control students (15%). Although bacterial pathogens were recovered from virus positive students with diarrhea, viral shedding also occurred independently of other agents. Clinical disease in students excreting only rotavirus tended to be mild and was accompanied by a low density of viral shedding. Food consumption in the home and at public eating establishments was examined the week before illness. While the location of food consumption was found to be important in the acquisition of diarrhea, there was no apparent relationship of the site where meals were eaten and the acquisition of rotavirus by students newly arrived in Mexico. These data support our previous study in a US student population residing in a rural setting in Mexico and implicate rotavirus as a cause of diarrhea among students traveling to Mexico from the United States. The present study offers additional evidence that rotavirus infection in this population might be spread by a nonfood vehicle of transmission which differs from spread of enterotoxigenic E coli, Shigella, or Salmonella strains in the same population.", "contents": "Human rotavirus in an adult population with travelers' diarrhea and its relationship to the location of food consumption. The role of human rotavirus in adult diarrhea was evaluated in 164 newly arrived US students attending summer school at an urban Mexican university. Rotavirus was identified in stool samples by electron microscopy. Rotavirus was found in 26 of 109 students with diarrhea (24%) and in 8 of 55 asymptomatic control students (15%). Although bacterial pathogens were recovered from virus positive students with diarrhea, viral shedding also occurred independently of other agents. Clinical disease in students excreting only rotavirus tended to be mild and was accompanied by a low density of viral shedding. Food consumption in the home and at public eating establishments was examined the week before illness. While the location of food consumption was found to be important in the acquisition of diarrhea, there was no apparent relationship of the site where meals were eaten and the acquisition of rotavirus by students newly arrived in Mexico. These data support our previous study in a US student population residing in a rural setting in Mexico and implicate rotavirus as a cause of diarrhea among students traveling to Mexico from the United States. The present study offers additional evidence that rotavirus infection in this population might be spread by a nonfood vehicle of transmission which differs from spread of enterotoxigenic E coli, Shigella, or Salmonella strains in the same population."}
{"id": "PMID:226657", "title": "Epidemiology of cytomegalovirus infection in end stage renal disease.", "content": "Since primary cytomegalovirus (CMV) infection is a cause of morbidity among renal transplant recipients, we undertook a prospective study of our maintenance hemodialysis patients and personnel to determine whether these sources posed a risk for transmission of CMV. Our study of 85 patients and 49 personnel showed that CMV was detected in eight nontransplanted, older dialysis patients and 13 patients who had lost their allograft. In spite of the presence of CMV on the unit, no patient or staff member developed primary infection from interpersonal transmission or from transfused frozen red blood cells. All primary infections in renal transplant patients could be accounted for by acquisition from the transplanted kidney, thus eliminating the dialysis unit or frozen blood as a risk to either patients or personnel.", "contents": "Epidemiology of cytomegalovirus infection in end stage renal disease. Since primary cytomegalovirus (CMV) infection is a cause of morbidity among renal transplant recipients, we undertook a prospective study of our maintenance hemodialysis patients and personnel to determine whether these sources posed a risk for transmission of CMV. Our study of 85 patients and 49 personnel showed that CMV was detected in eight nontransplanted, older dialysis patients and 13 patients who had lost their allograft. In spite of the presence of CMV on the unit, no patient or staff member developed primary infection from interpersonal transmission or from transfused frozen red blood cells. All primary infections in renal transplant patients could be accounted for by acquisition from the transplanted kidney, thus eliminating the dialysis unit or frozen blood as a risk to either patients or personnel."}
{"id": "PMID:226658", "title": "Profile of Mood States: the factors and their physiological correlates.", "content": "Spontaneously occurring mood states and various physiological indices were evaluated on three occasions in a group of eight healthy males. Results reveal that significant positive correlations exist among five of the six factors comprising the Profile of Mood States (POMS). This finding is related to previous research on the POMS and varied methodologies utilized in those reports. Reliable positive correlations of the POMS factors Depression and Tension with heart rate and diastolic blood pressure were obtained. The Anger factor of the POMS also correlated positively and significantly with heart rate. These findings are discussed in terms of the relationship between POMS factors and anxiety.", "contents": "Profile of Mood States: the factors and their physiological correlates. Spontaneously occurring mood states and various physiological indices were evaluated on three occasions in a group of eight healthy males. Results reveal that significant positive correlations exist among five of the six factors comprising the Profile of Mood States (POMS). This finding is related to previous research on the POMS and varied methodologies utilized in those reports. Reliable positive correlations of the POMS factors Depression and Tension with heart rate and diastolic blood pressure were obtained. The Anger factor of the POMS also correlated positively and significantly with heart rate. These findings are discussed in terms of the relationship between POMS factors and anxiety."}
{"id": "PMID:226659", "title": "Dopamine-sensitive adenylate cyclase activity in the caudate nucleus and adrenal medulla in Parkinson's disease and in liver cirrhosis.", "content": "In human caudate nucleus and adrenal medulla dopamine-stimulated adenylate cyclase was measured. At a concentration of 100 microM dopamine, liver cirrhosis, carcinoma and therapy resistent parkinsonian patients showed decreased stimulation or even a reduction compared to controls. Therapy responding parkinsonian patients showed a decreased stimulation compared to controls, but this stimulation was significantly higher than in drug resistent patients.", "contents": "Dopamine-sensitive adenylate cyclase activity in the caudate nucleus and adrenal medulla in Parkinson's disease and in liver cirrhosis. In human caudate nucleus and adrenal medulla dopamine-stimulated adenylate cyclase was measured. At a concentration of 100 microM dopamine, liver cirrhosis, carcinoma and therapy resistent parkinsonian patients showed decreased stimulation or even a reduction compared to controls. Therapy responding parkinsonian patients showed a decreased stimulation compared to controls, but this stimulation was significantly higher than in drug resistent patients."}
{"id": "PMID:226660", "title": "Correlated effects of acetylcholine and cyclic guanosine monophosphate on membrane properties of mammalian neocortical neurons.", "content": "The effects of successive extracellular iontophoresis of acetylcholine (ACh) and atropine, and intracellular hyperpolarizing iontophoresis of cyclic GMP (cGMP) were studied in single neurons of the coronal-pericruciate cortex of awake cats. (a) Fifty-seven percent of the neurons that were tested responded to ACh with an increase in neuronal input resistance (Rm) and 50% responded to ACh with an increase in firing rate; 65% responded to cGMP with an increase in Rm and 60% responded to cGMP with an increase in firing rate. (b) After application of atropine, increases in Rm and firing rate associated with iontophoresis of ACh failed to recur. (c) Persistent increases in Rm following application of ACh accompanied by current-induced neuronal discharge were not diminished by subsequent application of atropine. (d) Atropine did not prevent increases in Rm and firing rate associated with intracellular iontophoresis of cGMP. (e) All cells tested with both ACh and cGMP that were shown initially to respond to extracellular ACh with increases in Rm were later shown to have comparable responses to cGMP.", "contents": "Correlated effects of acetylcholine and cyclic guanosine monophosphate on membrane properties of mammalian neocortical neurons. The effects of successive extracellular iontophoresis of acetylcholine (ACh) and atropine, and intracellular hyperpolarizing iontophoresis of cyclic GMP (cGMP) were studied in single neurons of the coronal-pericruciate cortex of awake cats. (a) Fifty-seven percent of the neurons that were tested responded to ACh with an increase in neuronal input resistance (Rm) and 50% responded to ACh with an increase in firing rate; 65% responded to cGMP with an increase in Rm and 60% responded to cGMP with an increase in firing rate. (b) After application of atropine, increases in Rm and firing rate associated with iontophoresis of ACh failed to recur. (c) Persistent increases in Rm following application of ACh accompanied by current-induced neuronal discharge were not diminished by subsequent application of atropine. (d) Atropine did not prevent increases in Rm and firing rate associated with intracellular iontophoresis of cGMP. (e) All cells tested with both ACh and cGMP that were shown initially to respond to extracellular ACh with increases in Rm were later shown to have comparable responses to cGMP."}
{"id": "PMID:226662", "title": "Electrophysiological study of the peripheral nervous system in children. Changes in proximal and distal conduction velocities from birth to age 5 years.", "content": "Hoffman's reflex was evoked in the soleus muscle of 105 normal children from birth to age 5 years. This technique made it possible to determine conduction time and to estimate conduction velocity over the reflex arc. For 59 children, proprioceptive and motor distal nerve conduction velocities were calculated for the tibial nerve trunk. These measurements enabled the common changes for these three velocities to be described in terms of an exponential curve. Proximal conduction velocity has similar values to those of proprioceptive distal nerve fibres: it is always higher than motor nerve conduction velocity, but the difference gradually diminishes, remaining constant after the eighteenth month. Conduction time diminishes between birth and one year of age, whereas height increases. Then conduction time increases slowly, reaching at about age 5 years, when average height is 1050 mm, the value it had just after birth. For the child born at term, maturation of the nervous system is thus especially rapid during the first year of life.", "contents": "Electrophysiological study of the peripheral nervous system in children. Changes in proximal and distal conduction velocities from birth to age 5 years. Hoffman's reflex was evoked in the soleus muscle of 105 normal children from birth to age 5 years. This technique made it possible to determine conduction time and to estimate conduction velocity over the reflex arc. For 59 children, proprioceptive and motor distal nerve conduction velocities were calculated for the tibial nerve trunk. These measurements enabled the common changes for these three velocities to be described in terms of an exponential curve. Proximal conduction velocity has similar values to those of proprioceptive distal nerve fibres: it is always higher than motor nerve conduction velocity, but the difference gradually diminishes, remaining constant after the eighteenth month. Conduction time diminishes between birth and one year of age, whereas height increases. Then conduction time increases slowly, reaching at about age 5 years, when average height is 1050 mm, the value it had just after birth. For the child born at term, maturation of the nervous system is thus especially rapid during the first year of life."}
{"id": "PMID:226664", "title": "Postnatal rat sympathetic neurons in culture. II. Synaptic transmission by postnatal neurons.", "content": "1. It was shown in the preceding paper that postnatally derived rat superior cervical ganglion neurons (SCGN) will grow in dissociated cell culture and form functional synaptic connections with each other. In this report, synaptic transmission by the postnatal SCGN is detailed. 2. Synaptic interactions between SCGN were blocked by the nicotinic cholinergic antagonist hexamathonium (C-6), indicating that acetylcholine was the transmitter substance used by these neurons. This was found to be the case even for neurons taken from 12.5-wk-old animals. 3. In a few cases, the beta-adrenergic blocking agent, propranolol, was found to block synaptic potentials, suggesting that a catecholamine might be involved in the transmission process. The possible mechanisms of this involvement are discussed. 4. SCGN taken from up to 10-wk-old rats were able to form functional synaptic contacts with cocultured skeletal muscle cells. These interactions were sensitive to low external Ca2+ and to 1--2 microM d-tubocurarine (d-TC). 5. It is concluded that even adult SCGN retain a certain amount of neurotransmitter \"plasticity\" when grown under appropriate culture conditions. From the data on the neuron-neuron and SCGN-skeletal muscle interactions, it is suggested that a matching of presynaptic transmitter with postsynaptic receptor is a sufficient condition for the formation of functional nerve-target interactions.", "contents": "Postnatal rat sympathetic neurons in culture. II. Synaptic transmission by postnatal neurons. 1. It was shown in the preceding paper that postnatally derived rat superior cervical ganglion neurons (SCGN) will grow in dissociated cell culture and form functional synaptic connections with each other. In this report, synaptic transmission by the postnatal SCGN is detailed. 2. Synaptic interactions between SCGN were blocked by the nicotinic cholinergic antagonist hexamathonium (C-6), indicating that acetylcholine was the transmitter substance used by these neurons. This was found to be the case even for neurons taken from 12.5-wk-old animals. 3. In a few cases, the beta-adrenergic blocking agent, propranolol, was found to block synaptic potentials, suggesting that a catecholamine might be involved in the transmission process. The possible mechanisms of this involvement are discussed. 4. SCGN taken from up to 10-wk-old rats were able to form functional synaptic contacts with cocultured skeletal muscle cells. These interactions were sensitive to low external Ca2+ and to 1--2 microM d-tubocurarine (d-TC). 5. It is concluded that even adult SCGN retain a certain amount of neurotransmitter \"plasticity\" when grown under appropriate culture conditions. From the data on the neuron-neuron and SCGN-skeletal muscle interactions, it is suggested that a matching of presynaptic transmitter with postsynaptic receptor is a sufficient condition for the formation of functional nerve-target interactions."}
{"id": "PMID:226666", "title": "Simultaneously occurring salivary gland tumors of different types.", "content": "Two cases of simultaneously occurring salivary gland tumors of the parotid gland are reported. Both patients were women in the sixth decade of life. In the first patient, a carcinoma in pleomorphic adenoma and an oncocytoma were found in the right parotid gland. The second patient had an adenoid cystic carcinoma associated with a sebaceous cell adenoma. The addition of these cases to the previously published data brings the total number of simultaneously occurring salivary gland tumors of different types to ten.", "contents": "Simultaneously occurring salivary gland tumors of different types. Two cases of simultaneously occurring salivary gland tumors of the parotid gland are reported. Both patients were women in the sixth decade of life. In the first patient, a carcinoma in pleomorphic adenoma and an oncocytoma were found in the right parotid gland. The second patient had an adenoid cystic carcinoma associated with a sebaceous cell adenoma. The addition of these cases to the previously published data brings the total number of simultaneously occurring salivary gland tumors of different types to ten."}
{"id": "PMID:226667", "title": "Bilateral nephroblastoma in a horseshoe kidney.", "content": "A case of bilateral nephroblastoma in a horseshoe kidney is presented. It is the second to be reported in the international literature.", "contents": "Bilateral nephroblastoma in a horseshoe kidney. A case of bilateral nephroblastoma in a horseshoe kidney is presented. It is the second to be reported in the international literature."}
{"id": "PMID:226669", "title": "Reduction of opiate binding to brainstem slices associated with the development of tolerance to morphine in rats.", "content": "Previous studies revealed that the characteristics of opiate binding sites are different in brainstem slices and homogenates. In the present study, the binding of opiate agonists, morphine and etorphine, and that of the antagonist, naloxone, to thin slices of rat brain stem was studied. Sodium ion inhibits agonist binding and enhances antagonist binding in brainstem slices. Development of the analgesic tolerance to morphine is accompanied by a reduction of opiate binding. The opiate binding recovers partially toward control values during morphine withdrawal. Kinetic analyses indicate that sodium-induced changes in opiate binding sites are different from those caused by chronic morphine treatment. These results provide evidence that analgesic tolerance is associated with changes in opiate receptors.", "contents": "Reduction of opiate binding to brainstem slices associated with the development of tolerance to morphine in rats. Previous studies revealed that the characteristics of opiate binding sites are different in brainstem slices and homogenates. In the present study, the binding of opiate agonists, morphine and etorphine, and that of the antagonist, naloxone, to thin slices of rat brain stem was studied. Sodium ion inhibits agonist binding and enhances antagonist binding in brainstem slices. Development of the analgesic tolerance to morphine is accompanied by a reduction of opiate binding. The opiate binding recovers partially toward control values during morphine withdrawal. Kinetic analyses indicate that sodium-induced changes in opiate binding sites are different from those caused by chronic morphine treatment. These results provide evidence that analgesic tolerance is associated with changes in opiate receptors."}
{"id": "PMID:226670", "title": "Adrenergic innervation and cyclic adenosine 3':5'-monophosphate levels in response to norepinephrine in stomach of postnatal rats.", "content": "Changes in receptor function, innervation and cyclic adenosine 3':5'-monophosphate (cAMP) levels in response to norepinephrine were investigated in the stomach of postnatal developing rats. We found that although the beta adrenergic receptor function and responsiveness of cAMP-generating system to norepinephrine are present in the early postnatal stage (3-day-old), these systems are not fully developed at birth and that increase in sensitivity comes with age. Adrenergic innervation is present at birth in Auerbach's plexus but not in smooth muscle, during the 1st postnatal week. Direct adrenergic innervation to smooth muscle appears 1 week after birth and matures during the first 4 weeks. This maturation of direct adrenergic innervation runs in parallel with the increased sensitivity of beta receptors and is accompanied by an elevated responsiveness of the cAMP-generating system to norepinephrine.", "contents": "Adrenergic innervation and cyclic adenosine 3':5'-monophosphate levels in response to norepinephrine in stomach of postnatal rats. Changes in receptor function, innervation and cyclic adenosine 3':5'-monophosphate (cAMP) levels in response to norepinephrine were investigated in the stomach of postnatal developing rats. We found that although the beta adrenergic receptor function and responsiveness of cAMP-generating system to norepinephrine are present in the early postnatal stage (3-day-old), these systems are not fully developed at birth and that increase in sensitivity comes with age. Adrenergic innervation is present at birth in Auerbach's plexus but not in smooth muscle, during the 1st postnatal week. Direct adrenergic innervation to smooth muscle appears 1 week after birth and matures during the first 4 weeks. This maturation of direct adrenergic innervation runs in parallel with the increased sensitivity of beta receptors and is accompanied by an elevated responsiveness of the cAMP-generating system to norepinephrine."}
{"id": "PMID:226671", "title": "Nicotinic, muscarinic and adrenergic receptors in a parasympathetic ganglion.", "content": "Transmission in submandibular ganglia of hamsters was blocked by hexamethonium and dimethylphenylpiperazinium. Dimethylphenylpiperazinium caused depolarization and decreased membrane resistance (Rm). The muscarinic agonist, bethanechol (BCh) caused depolarization of some cells and hyperpolarization of others. Regardless of the change in membrane potential, BCh always increased Rm. Since the responses to BCh persisted in the absence of [Ca++]0, it was concluded that BCh acted directly on the ganglion cells and did not depend upon a transsynaptic process. All responses to BCh were prevented by atropine. The evidence suggests that the ganglion cells possess muscarinic receptors. Like BCh, norepinephrine (NE) either depolarized or hyperpolarized the ganglion cells. There was no relationship between the blockade of transmission by NE and the effect of NE on the membrane potential. The responses to NE were prevented by dihydroergotamine, suggesting the presence of alpha adrenergic receptors on the ganglion cells.", "contents": "Nicotinic, muscarinic and adrenergic receptors in a parasympathetic ganglion. Transmission in submandibular ganglia of hamsters was blocked by hexamethonium and dimethylphenylpiperazinium. Dimethylphenylpiperazinium caused depolarization and decreased membrane resistance (Rm). The muscarinic agonist, bethanechol (BCh) caused depolarization of some cells and hyperpolarization of others. Regardless of the change in membrane potential, BCh always increased Rm. Since the responses to BCh persisted in the absence of [Ca++]0, it was concluded that BCh acted directly on the ganglion cells and did not depend upon a transsynaptic process. All responses to BCh were prevented by atropine. The evidence suggests that the ganglion cells possess muscarinic receptors. Like BCh, norepinephrine (NE) either depolarized or hyperpolarized the ganglion cells. There was no relationship between the blockade of transmission by NE and the effect of NE on the membrane potential. The responses to NE were prevented by dihydroergotamine, suggesting the presence of alpha adrenergic receptors on the ganglion cells."}
{"id": "PMID:226673", "title": "Catecholaminergic alpha-receptors and shivering in the rat.", "content": "1. A rise or a fall in systemic blood pressure brought about by the I.V. infusion of peripherally acting drugs (adenosine, noradrenaline or methoxamine) inhibited shivering in the cold-exposed rat. 2. Since the injection of commonly used doses of noradrenaline (0.05-0.10 mumole) into a lateral cerebral ventricle of a rat was usually accompanied by a rise in blood pressure special precautious were required to determine whether noradrenaline had a specific central effect on shivering. 3. Small doses of noradrenaline (0.02-0.03 mumole) or clonidine (0.01 mumole) which had no effect on blood pressure when injected into a lateral cerebral ventricle still inhibited shivering in the cold-exposed rat and this effect was prevented by phentolamine. 4. It is concluded that noradrenaline can inhibit the cold sensor-shivering pathway in its central course by an action on alpha-receptors.", "contents": "Catecholaminergic alpha-receptors and shivering in the rat. 1. A rise or a fall in systemic blood pressure brought about by the I.V. infusion of peripherally acting drugs (adenosine, noradrenaline or methoxamine) inhibited shivering in the cold-exposed rat. 2. Since the injection of commonly used doses of noradrenaline (0.05-0.10 mumole) into a lateral cerebral ventricle of a rat was usually accompanied by a rise in blood pressure special precautious were required to determine whether noradrenaline had a specific central effect on shivering. 3. Small doses of noradrenaline (0.02-0.03 mumole) or clonidine (0.01 mumole) which had no effect on blood pressure when injected into a lateral cerebral ventricle still inhibited shivering in the cold-exposed rat and this effect was prevented by phentolamine. 4. It is concluded that noradrenaline can inhibit the cold sensor-shivering pathway in its central course by an action on alpha-receptors."}
{"id": "PMID:226681", "title": "Supportive nursing: a critical review of the literature.", "content": "Nurses have long thought that providing support was a part, if not a central part, of their nursing practice. In the literature, nurses have described their ability to provide support and have discussed their inability as well as their reasons why they have been unable to give support. Support for nurses has at least three parameters: physical, social, and emotional. The emotional parameter has received the most attention by nurses. The meaning of support in nursing needs to be clearer and more precise. Although several nurses, either through theoretical discussions or exploratory research studies, have begun to further define support, this construct warrants more thought and investigation by nurses. Once an operational definition is determined and supportive behaviors identified, nurses can further investigate the influence of support to the promotion of health.", "contents": "Supportive nursing: a critical review of the literature. Nurses have long thought that providing support was a part, if not a central part, of their nursing practice. In the literature, nurses have described their ability to provide support and have discussed their inability as well as their reasons why they have been unable to give support. Support for nurses has at least three parameters: physical, social, and emotional. The emotional parameter has received the most attention by nurses. The meaning of support in nursing needs to be clearer and more precise. Although several nurses, either through theoretical discussions or exploratory research studies, have begun to further define support, this construct warrants more thought and investigation by nurses. Once an operational definition is determined and supportive behaviors identified, nurses can further investigate the influence of support to the promotion of health."}
{"id": "PMID:226693", "title": "Microscopic observations on the filopodia of Entamoeba histolytica.", "content": "Living Entamoeba histolytica trophozoites were examined by phase-contrast microscopy. Intact critical point dried trophozoites were examined by transmission electron microscopy at an accelerating voltage of 1000 kV (HVEM) and by scanning electron microscopy (SEM). Half and quarter micrometer thick sections of epoxy-embedded trophozoites were examined by HVEM. Many of the trophozoites of 2 strains examined had surface filopodia, 1 to over 100 micrometers in length. The cytoplasm of filopodia was continuous with the cytoplasm and bounded by surface plasmalemma bearing a glycocalyx. Structures called \"surface-active lysosomes with trigger,\" \"dendritic plasmalemmal extensions,\" and \"extra-amebic vesicles\" by previous investigators probably represent portions of filopodia demonstrated in the present study. Filopodia appear to be of frequent normal occurrence in E. histolytica and may function in: (a) endocytosis or pinocytosis; (b) exocytosis; (c) attachment to substratum; (d) penetration of tissue; (e) release of cytotoxic substances; or (f) contact cytolysis of host cells.", "contents": "Microscopic observations on the filopodia of Entamoeba histolytica. Living Entamoeba histolytica trophozoites were examined by phase-contrast microscopy. Intact critical point dried trophozoites were examined by transmission electron microscopy at an accelerating voltage of 1000 kV (HVEM) and by scanning electron microscopy (SEM). Half and quarter micrometer thick sections of epoxy-embedded trophozoites were examined by HVEM. Many of the trophozoites of 2 strains examined had surface filopodia, 1 to over 100 micrometers in length. The cytoplasm of filopodia was continuous with the cytoplasm and bounded by surface plasmalemma bearing a glycocalyx. Structures called \"surface-active lysosomes with trigger,\" \"dendritic plasmalemmal extensions,\" and \"extra-amebic vesicles\" by previous investigators probably represent portions of filopodia demonstrated in the present study. Filopodia appear to be of frequent normal occurrence in E. histolytica and may function in: (a) endocytosis or pinocytosis; (b) exocytosis; (c) attachment to substratum; (d) penetration of tissue; (e) release of cytotoxic substances; or (f) contact cytolysis of host cells."}
{"id": "PMID:226694", "title": "Trichomonas vaginalis resistance to Mengo virus infection.", "content": "We have investigated the susceptibility of Trichomonas vaginalis to Mengo virus infection by comparing the outcome of Mengo virus or purified Mengo virus RNA infection in T. vaginalis and in CCL-1 mouse fibroblasts. While the adsorption and entry of Mengo virus into T. vaginalis occurred in the same manner as in fibroblasts, the uncoating was much slower. In addition, Mengo virus infection of T. vaginalis displayed no eclipse nor any subsequent production of infectious virus. Purified RNA failed to initiate productive infection in T. vaginalis, whereas it provoked viral replication in the fibroblast controls. It was shown by assessment of protein synthesis in T. vaginalis and mouse fibroblasts cell-free systems that the protozoan ribosomes were able to translate endogenous mRNA and poly-U, but not viral RNA.", "contents": "Trichomonas vaginalis resistance to Mengo virus infection. We have investigated the susceptibility of Trichomonas vaginalis to Mengo virus infection by comparing the outcome of Mengo virus or purified Mengo virus RNA infection in T. vaginalis and in CCL-1 mouse fibroblasts. While the adsorption and entry of Mengo virus into T. vaginalis occurred in the same manner as in fibroblasts, the uncoating was much slower. In addition, Mengo virus infection of T. vaginalis displayed no eclipse nor any subsequent production of infectious virus. Purified RNA failed to initiate productive infection in T. vaginalis, whereas it provoked viral replication in the fibroblast controls. It was shown by assessment of protein synthesis in T. vaginalis and mouse fibroblasts cell-free systems that the protozoan ribosomes were able to translate endogenous mRNA and poly-U, but not viral RNA."}
{"id": "PMID:226695", "title": "Growth response of axenic Entamoeba histolytica to hydrogen, carbon dioxide, and oxygen.", "content": "Entamoeba histolytica required CO2 for growth in axenic culture while growth was inhibited by H2. The organism was tolerant to 5% O2 in the gas phase and it was able to detoxify products of O2 reduction in the medium. The ameba did not require a negative oxidation-reduction potential for axenic growth. However, little or no free O2 was present in media exposed to 5% O2 in the gas phase. Growth was improved by adding yeast extract to the medium.", "contents": "Growth response of axenic Entamoeba histolytica to hydrogen, carbon dioxide, and oxygen. Entamoeba histolytica required CO2 for growth in axenic culture while growth was inhibited by H2. The organism was tolerant to 5% O2 in the gas phase and it was able to detoxify products of O2 reduction in the medium. The ameba did not require a negative oxidation-reduction potential for axenic growth. However, little or no free O2 was present in media exposed to 5% O2 in the gas phase. Growth was improved by adding yeast extract to the medium."}
{"id": "PMID:226697", "title": "Antitumor immunity in breast cancer patients. Biologic and therapeutic implications.", "content": "As judged by in vivo and in vitro indices of cellular immunity, mammary carcinogenesis appears to be associated with immunogenic changes in the transformed cells and prognostically favorable antitumor cell-mediated immunity in the host. The prognostically favorable cell-mediated immunity appears to be directed against a component(s) which is shared by most stage 0 in situ breast cancers and the major envelope glycoprotein (gp55) of RIII murine mammary tumor virus. Progressive disease is associated with a loss of gp55-like tumor immunogenicity and/or anti-gp55 cell-mediated immunity of the host. It is appropriate that measurements of tumor immunogenicity and tumor-specific cell-mediated immunity of the host be included in the prognostic assessment and therapeutic decisions regarding individual patients. Such data are particularly pernitent to the development and evaluation of immunotherapeutic and immunoprophylactic protocols.", "contents": "Antitumor immunity in breast cancer patients. Biologic and therapeutic implications. As judged by in vivo and in vitro indices of cellular immunity, mammary carcinogenesis appears to be associated with immunogenic changes in the transformed cells and prognostically favorable antitumor cell-mediated immunity in the host. The prognostically favorable cell-mediated immunity appears to be directed against a component(s) which is shared by most stage 0 in situ breast cancers and the major envelope glycoprotein (gp55) of RIII murine mammary tumor virus. Progressive disease is associated with a loss of gp55-like tumor immunogenicity and/or anti-gp55 cell-mediated immunity of the host. It is appropriate that measurements of tumor immunogenicity and tumor-specific cell-mediated immunity of the host be included in the prognostic assessment and therapeutic decisions regarding individual patients. Such data are particularly pernitent to the development and evaluation of immunotherapeutic and immunoprophylactic protocols."}
{"id": "PMID:226699", "title": "Malignant trophoblastic disease in paraguay.", "content": "The incidence of malignant trophoblastic diseases from 1960 to 1969 and 1970 to 1974 in the population of Parguay was low, as shown by the analysis of unselected hospital admissions as compared to the total population. Paraguay showed disease characteristics comparable to those of developing countries where malignant diseases of the trophoblast have elevated frequencies. The apparently high frequencies in lower socioeconomic groups appear to be due to the fact that these groups make up a large proportion of the hospital population. The hardship of poverty predisposes to the hospital concentration of pathologic pregnancies from around the country and to the home delivery of grossly normal gestations. Thus, a biased incidence of diseases results.", "contents": "Malignant trophoblastic disease in paraguay. The incidence of malignant trophoblastic diseases from 1960 to 1969 and 1970 to 1974 in the population of Parguay was low, as shown by the analysis of unselected hospital admissions as compared to the total population. Paraguay showed disease characteristics comparable to those of developing countries where malignant diseases of the trophoblast have elevated frequencies. The apparently high frequencies in lower socioeconomic groups appear to be due to the fact that these groups make up a large proportion of the hospital population. The hardship of poverty predisposes to the hospital concentration of pathologic pregnancies from around the country and to the home delivery of grossly normal gestations. Thus, a biased incidence of diseases results."}
{"id": "PMID:226702", "title": "Cellular antiproliferative action exerted by auranofin.", "content": "Auranofin (AF) is a new orally absorbed coordinated gold compound currently undergoing Phase I studies for its use in the treatment of rheumatoid arthritis. Our investigations with RAJI lymphoma, HeLa carcinoma, and EBV-transformed cells indicate AF exerts an inhibitory effect on DNA, RNA, and protein synthesis as assessed by 3H-thymidine, 3H-uridine, and 3H-leucine uptake, respectively. A rapid and persistent dose dependent inhibition of 3H-thymidine uptake was observed at gold concentrations of 50-100 microgram/dl while all parameters were inhibited after a 24 hr exposure to 100 microgram/dl. Reductions in viability and surface morphological changes were also observed. These results suggest AF exerts a significant inhibitory effect on essential biological processes and functions.", "contents": "Cellular antiproliferative action exerted by auranofin. Auranofin (AF) is a new orally absorbed coordinated gold compound currently undergoing Phase I studies for its use in the treatment of rheumatoid arthritis. Our investigations with RAJI lymphoma, HeLa carcinoma, and EBV-transformed cells indicate AF exerts an inhibitory effect on DNA, RNA, and protein synthesis as assessed by 3H-thymidine, 3H-uridine, and 3H-leucine uptake, respectively. A rapid and persistent dose dependent inhibition of 3H-thymidine uptake was observed at gold concentrations of 50-100 microgram/dl while all parameters were inhibited after a 24 hr exposure to 100 microgram/dl. Reductions in viability and surface morphological changes were also observed. These results suggest AF exerts a significant inhibitory effect on essential biological processes and functions."}
{"id": "PMID:226703", "title": "Synthesis of 11 beta,13 beta- and 13 beta,16 beta-propano steroids: probes of hormonal activity.", "content": "Syntheses of 11 beta,13 beta- and 13 beta,16 beta-propano derivatives of 17 alpha-ethynyl-17 beta-hydroxygon-4-en-3-one are described. The 13 beta,16 beta bridge was constructed by intramolecular alkylation of the C-16 enolate anion from 3-methoxy-13 beta-[3'-(tosyloxy)propyl]gona-3,5-dien-17-one, the latter being obtained via Birch reduction of both aryl groups of 17 beta-hydroxy-3-methoxy-13 beta-(3'-phenoxypropyl)gona-1,3,5(10),8-tetraene (1). The 11 beta,13 beta bridge was constructed by Prins cyclization of 17 beta-acetoxy-3-methoxy-13 beta-(3'-oxopropyl)gona-1,3,5(10),9(11)-tetraene, itself obtained via Birch reduction of only the side-chain aryl group of 1. Binding affinities of certain of these compounds and substituted 13 beta-propyl derivatives of 17 alpha-ethynyl-17 beta-hydroxygon-4-en-3-one for the uterine cytosol receptor of progesterone are reported, and the origin of the high progestational activity of norgestrel and 11 beta-substituted progestins is discussed.", "contents": "Synthesis of 11 beta,13 beta- and 13 beta,16 beta-propano steroids: probes of hormonal activity. Syntheses of 11 beta,13 beta- and 13 beta,16 beta-propano derivatives of 17 alpha-ethynyl-17 beta-hydroxygon-4-en-3-one are described. The 13 beta,16 beta bridge was constructed by intramolecular alkylation of the C-16 enolate anion from 3-methoxy-13 beta-[3'-(tosyloxy)propyl]gona-3,5-dien-17-one, the latter being obtained via Birch reduction of both aryl groups of 17 beta-hydroxy-3-methoxy-13 beta-(3'-phenoxypropyl)gona-1,3,5(10),8-tetraene (1). The 11 beta,13 beta bridge was constructed by Prins cyclization of 17 beta-acetoxy-3-methoxy-13 beta-(3'-oxopropyl)gona-1,3,5(10),9(11)-tetraene, itself obtained via Birch reduction of only the side-chain aryl group of 1. Binding affinities of certain of these compounds and substituted 13 beta-propyl derivatives of 17 alpha-ethynyl-17 beta-hydroxygon-4-en-3-one for the uterine cytosol receptor of progesterone are reported, and the origin of the high progestational activity of norgestrel and 11 beta-substituted progestins is discussed."}
{"id": "PMID:226704", "title": "Photoaffinity labeling of the angiotensin II receptor. 3. Receptor inactivation with photolabile hormone analogues.", "content": "It has been shown that the receptor of angiotensin II (AT) in rabbit aorta strips, rat aorta, and rat stomach can be blocked specifically and irreversibly by several photolabile analogues of Sar-Arg-Val-Tyr-Val-His-Pro-Phe ([Sar1]AT) with irradiation. The effectiveness of a photolabel with light of wavelength 365 nm depends on the labeling amino acid (L-4'-nitrophenylalanine, L-4'-diazoniumphenylalanine, or L-4'-azidophenylalanine) and on its position in the peptide (replacing Tyr4 and/or Phe8). The 4'-azido)Phe-containing analogues are all good to fair photoinactivators. Their decreasing order of effectiveness is as follows: [Sar1,(4'-azido)Phe8]AT, [Sar1,(4'-azido)Phe4,8]AT, and [Sar1,(4'-azidoPhe4]AT. The (4'-nitro)Phe analogues show the opposite relation: the good ligand [Sar1,(4'-nitro)Phe8]AT is almost ineffective, but the nonligand [Sar1,(4-nitro)Phe4]AT exhibits good, specific photoinactivation. This can be explained by the existence of a different photolysis pathway for (4'-nitro)Phe: this analogue probably undergoes a multiphoton decay with a long-lived first excited state. A peptide in this state may differ in its pharmacological properties from the ground state and become a ligand.", "contents": "Photoaffinity labeling of the angiotensin II receptor. 3. Receptor inactivation with photolabile hormone analogues. It has been shown that the receptor of angiotensin II (AT) in rabbit aorta strips, rat aorta, and rat stomach can be blocked specifically and irreversibly by several photolabile analogues of Sar-Arg-Val-Tyr-Val-His-Pro-Phe ([Sar1]AT) with irradiation. The effectiveness of a photolabel with light of wavelength 365 nm depends on the labeling amino acid (L-4'-nitrophenylalanine, L-4'-diazoniumphenylalanine, or L-4'-azidophenylalanine) and on its position in the peptide (replacing Tyr4 and/or Phe8). The 4'-azido)Phe-containing analogues are all good to fair photoinactivators. Their decreasing order of effectiveness is as follows: [Sar1,(4'-azido)Phe8]AT, [Sar1,(4'-azido)Phe4,8]AT, and [Sar1,(4'-azidoPhe4]AT. The (4'-nitro)Phe analogues show the opposite relation: the good ligand [Sar1,(4'-nitro)Phe8]AT is almost ineffective, but the nonligand [Sar1,(4-nitro)Phe4]AT exhibits good, specific photoinactivation. This can be explained by the existence of a different photolysis pathway for (4'-nitro)Phe: this analogue probably undergoes a multiphoton decay with a long-lived first excited state. A peptide in this state may differ in its pharmacological properties from the ground state and become a ligand."}
{"id": "PMID:226705", "title": "Synthesis and biological properties of N2-substituted spin-labeled analogues of actinomycin D.", "content": "We have synthesized N2-[4-(2,2,6,6-tetramethyl-1-piperidinyloxy)]actinomycin D And the related 1,2-diaminoethane and 1,3-diaminopropane derivatives and evaluated their biological properties. Binding studies with the spin-labeled actinomycin D analogues and DNA were carried out by using circular dichroism, electron spin resonance, and thermal denaturation. These studies have suggested that the derivatives bind to DNA and that their DNA-binding modes are similar but not identical. Spin-labeled actinomycin D derivatives were less potent in inhibiting Escherichia coli DNA-dependent RNA polymerase reaction than actinomycin D and were less toxic to L1210 cells in vitro than the parent compound. Spin-labeled actinomycin D derivatives were more common than the parent compounds against P-388 leukemia cells in vitro with little or no toxicity.", "contents": "Synthesis and biological properties of N2-substituted spin-labeled analogues of actinomycin D. We have synthesized N2-[4-(2,2,6,6-tetramethyl-1-piperidinyloxy)]actinomycin D And the related 1,2-diaminoethane and 1,3-diaminopropane derivatives and evaluated their biological properties. Binding studies with the spin-labeled actinomycin D analogues and DNA were carried out by using circular dichroism, electron spin resonance, and thermal denaturation. These studies have suggested that the derivatives bind to DNA and that their DNA-binding modes are similar but not identical. Spin-labeled actinomycin D derivatives were less potent in inhibiting Escherichia coli DNA-dependent RNA polymerase reaction than actinomycin D and were less toxic to L1210 cells in vitro than the parent compound. Spin-labeled actinomycin D derivatives were more common than the parent compounds against P-388 leukemia cells in vitro with little or no toxicity."}
{"id": "PMID:226701", "title": "Crystal-induced inflammation, enzyme release and the effects of drugs in the rat pleural space.", "content": "The pleural space of the rat has been used to study the acute inflammatory response to crystals of monosodium urate monohydrate, calcium pyrophosphate dihydrate and hydroxyapatite. Each crystal caused a brisk inflammatory response accompanied by crystal phagocytosis and release of lysosomal enzymes. These responses were modified by the anti-inflammatory drugs indomethacin, dexamethasone, colchicine and cyclophosphamide. The results of these experiments suggesting that the resting cell population of the pleural space contributed to the response, and that lysosomal enzyme release may play only a minor role in the mediation of increased vascular permeability.", "contents": "Crystal-induced inflammation, enzyme release and the effects of drugs in the rat pleural space. The pleural space of the rat has been used to study the acute inflammatory response to crystals of monosodium urate monohydrate, calcium pyrophosphate dihydrate and hydroxyapatite. Each crystal caused a brisk inflammatory response accompanied by crystal phagocytosis and release of lysosomal enzymes. These responses were modified by the anti-inflammatory drugs indomethacin, dexamethasone, colchicine and cyclophosphamide. The results of these experiments suggesting that the resting cell population of the pleural space contributed to the response, and that lysosomal enzyme release may play only a minor role in the mediation of increased vascular permeability."}
{"id": "PMID:226706", "title": "Frequency sweep analysis of neuromuscular junction continuity.", "content": "A new technique for measuring neuromuscular junction continuity is described. Junctional transmission is evaluated by integration of the electromyographic (EMG) response induced by intramuscular electrical stimulation. The unique characteristics of this monitoring technique are the use of intramuscular stimulation and a varying stimulation rate. The stimulus frequency is made to increase exponentially from 1 to 100 pulses per second over a period of 10 or 15 seconds. Thin coiled wire electrodes are used for stimulation and recording of the EMG response. The frequency sweep electromyogram (FS-EMB) response was measured in uncurarized and curarized tibialis anterior muscle of cat. In the uncurarized preparation, the FS-EMG response was only slightly decreased with an increasing stimulus frequency. During neuromuscular blockade with d-tubocurarine the FS-EMG response diminished with increasing frequency. The response failed at successively lower frequencies during deeper levels of neuromuscular block. Recovery proceeded in the reverse order. The frequency sweep technique provides quantitative assessment of neuromuscular junction continuity over a broad spectrum of driving frequencies without inducing fatigue. This method does not require force measurements nor voluntary effort. Intramuscular stimulation minimises painful stimuli thus making the frequency sweep technique suitable for evaluating neuromuscular transmission in either conscious or unconscious individuals.", "contents": "Frequency sweep analysis of neuromuscular junction continuity. A new technique for measuring neuromuscular junction continuity is described. Junctional transmission is evaluated by integration of the electromyographic (EMG) response induced by intramuscular electrical stimulation. The unique characteristics of this monitoring technique are the use of intramuscular stimulation and a varying stimulation rate. The stimulus frequency is made to increase exponentially from 1 to 100 pulses per second over a period of 10 or 15 seconds. Thin coiled wire electrodes are used for stimulation and recording of the EMG response. The frequency sweep electromyogram (FS-EMB) response was measured in uncurarized and curarized tibialis anterior muscle of cat. In the uncurarized preparation, the FS-EMG response was only slightly decreased with an increasing stimulus frequency. During neuromuscular blockade with d-tubocurarine the FS-EMG response diminished with increasing frequency. The response failed at successively lower frequencies during deeper levels of neuromuscular block. Recovery proceeded in the reverse order. The frequency sweep technique provides quantitative assessment of neuromuscular junction continuity over a broad spectrum of driving frequencies without inducing fatigue. This method does not require force measurements nor voluntary effort. Intramuscular stimulation minimises painful stimuli thus making the frequency sweep technique suitable for evaluating neuromuscular transmission in either conscious or unconscious individuals."}
{"id": "PMID:226707", "title": "Conformational changes of membrane-bound (Na+--K+)-ATPase as revealed by trypsin digestion.", "content": "To distinguish ligand-induced structural states of the (Na+--K+)-ATPase, the purified membrane-bound enzyme isolated from rat kidneys was digested with trypsin in the presence of various combinations of Na+, K+, Mg++ and ATP. It was found that first the large and then the small polypeptide chain of the (Na+--K+)-ATPase was degraded, indicating that the lysine and arginine residues of the large chain are more exposed than are those of the small one. The (Na+--K+)-ATPase activity was inactivated in parallel with the degradation of the large polypeptide chain. After the degradation of the large polypeptide chain, about 75% of the (Na+--K+)-ATPase protein remained bound to the membrane, demonstrating that the split protein segments were only partially released. It was found that the combinations of ATP, Mg++, Na+ and K+ present during trypsin digestion influenced the time course and degree of degradation of the (Na+--K+)-ATPase protein. The degradations of the large and the small polypeptide chain were affected in parallel. Thus, certain ATP and ligand combinations influenced neither the degradation of the large nor the degradation of the small polypeptide chain, whereas by other combinations of ATP and ligands the degree of susceptibility of both polypeptide chains to trypsin was equally increased or reduced. In the absence of ATP the time course of trypsin digestion of the (Na+--K+)-ATPase was the same, whether Na+ or K+ was present. With low ATP concentrations (e.g., 0.1 mM), however, binding of Na+ or K+ led to different degradation patterns of the enzyme. If a high concentration of ATP (e.g. 10 mM) was present, Na+ and K+ also influenced the degradation pattern of the (Na+--K+)-ATPase, but differentially compared to that at low ATP concentrations, since the effects of Na+ and K+ were reversed. Furthermore, it was found that the degradation of the small chain was only influenced by certain combinations of ATP, Mg++, Na+ and K+ if the large chain was intact when the ligands were added to the enzyme. The described results demonstrate structural alterations of the (Na+--K+)-ATPase complex which are supposed to include a synchronous protrusion or retraction of both (Na+--K+)-ATPase subunits. The data further suggest that ATP and other ligands primarily alter the structure of the large (Na+--K+)-ATPase subunit. This structural alteration is presumed to lead to a synchronous movement of the small subunit of the enzyme. The structural state of the (Na+--K+)-ATPase is regulated by binding of Na+ or K+ to the enzyme-ATP complex. The effects of Na+ and K+ on the (Na+--K+)-ATPase structure are modulated by the ATP binding to \"high affinity\" and to \"low affinity\" ATP binding sites.", "contents": "Conformational changes of membrane-bound (Na+--K+)-ATPase as revealed by trypsin digestion. To distinguish ligand-induced structural states of the (Na+--K+)-ATPase, the purified membrane-bound enzyme isolated from rat kidneys was digested with trypsin in the presence of various combinations of Na+, K+, Mg++ and ATP. It was found that first the large and then the small polypeptide chain of the (Na+--K+)-ATPase was degraded, indicating that the lysine and arginine residues of the large chain are more exposed than are those of the small one. The (Na+--K+)-ATPase activity was inactivated in parallel with the degradation of the large polypeptide chain. After the degradation of the large polypeptide chain, about 75% of the (Na+--K+)-ATPase protein remained bound to the membrane, demonstrating that the split protein segments were only partially released. It was found that the combinations of ATP, Mg++, Na+ and K+ present during trypsin digestion influenced the time course and degree of degradation of the (Na+--K+)-ATPase protein. The degradations of the large and the small polypeptide chain were affected in parallel. Thus, certain ATP and ligand combinations influenced neither the degradation of the large nor the degradation of the small polypeptide chain, whereas by other combinations of ATP and ligands the degree of susceptibility of both polypeptide chains to trypsin was equally increased or reduced. In the absence of ATP the time course of trypsin digestion of the (Na+--K+)-ATPase was the same, whether Na+ or K+ was present. With low ATP concentrations (e.g., 0.1 mM), however, binding of Na+ or K+ led to different degradation patterns of the enzyme. If a high concentration of ATP (e.g. 10 mM) was present, Na+ and K+ also influenced the degradation pattern of the (Na+--K+)-ATPase, but differentially compared to that at low ATP concentrations, since the effects of Na+ and K+ were reversed. Furthermore, it was found that the degradation of the small chain was only influenced by certain combinations of ATP, Mg++, Na+ and K+ if the large chain was intact when the ligands were added to the enzyme. The described results demonstrate structural alterations of the (Na+--K+)-ATPase complex which are supposed to include a synchronous protrusion or retraction of both (Na+--K+)-ATPase subunits. The data further suggest that ATP and other ligands primarily alter the structure of the large (Na+--K+)-ATPase subunit. This structural alteration is presumed to lead to a synchronous movement of the small subunit of the enzyme. The structural state of the (Na+--K+)-ATPase is regulated by binding of Na+ or K+ to the enzyme-ATP complex. The effects of Na+ and K+ on the (Na+--K+)-ATPase structure are modulated by the ATP binding to \"high affinity\" and to \"low affinity\" ATP binding sites."}
{"id": "PMID:226708", "title": "Phosphorylation of casein by human erythrocyte membrane-bound protein kinase: competition of casein with endogenous substrates.", "content": "The possibility that spectrin and band-3 protein are phosphorylated by the same membrane-bound protein kinase was investigated by adding casein to unsealed erythrocyte ghosts and examing competition of the three proteins for phosphorylation. The extent of spectrin and band-3 protein phosphorylation was reduced by up to approximately 55%. This indicated that casein was competing with these endogenous substrates for phosphorylation and was most probably phosphorylated by the same protein kinase(s). Furthermore, the extent of inhibition of the phosphorylation of the two endogenous substrates was indistinguishable over the range of casein concentrations tested (0.1 to 5 mg/ml). This indicates that spectrin and band-3 protein may be phosphorylated by the same protein kinase. In contrast, casein was found to have no effect on the cAMP-dependent phosphorylation of band 4.5. This result indicates that casein only competes with the endogenous proteins phosphorylated by the cAMP-independent protein kinase(s). The extent of reduction of endogenous substrate phosphorylation in the presence of casein was found to be constant over incubation periods of 1 to 15 min, indicating that this reduction was not due to consumption of ATP. Since the spectrin and band-3 protein phosphorylations were specifically and identically reduced by casein and these reductions were not due to the ATP consumption or to a general alteration of the membrane, we conclude that the two substrates are likely phosphorylated by one kinase which also phosphorylates casein.", "contents": "Phosphorylation of casein by human erythrocyte membrane-bound protein kinase: competition of casein with endogenous substrates. The possibility that spectrin and band-3 protein are phosphorylated by the same membrane-bound protein kinase was investigated by adding casein to unsealed erythrocyte ghosts and examing competition of the three proteins for phosphorylation. The extent of spectrin and band-3 protein phosphorylation was reduced by up to approximately 55%. This indicated that casein was competing with these endogenous substrates for phosphorylation and was most probably phosphorylated by the same protein kinase(s). Furthermore, the extent of inhibition of the phosphorylation of the two endogenous substrates was indistinguishable over the range of casein concentrations tested (0.1 to 5 mg/ml). This indicates that spectrin and band-3 protein may be phosphorylated by the same protein kinase. In contrast, casein was found to have no effect on the cAMP-dependent phosphorylation of band 4.5. This result indicates that casein only competes with the endogenous proteins phosphorylated by the cAMP-independent protein kinase(s). The extent of reduction of endogenous substrate phosphorylation in the presence of casein was found to be constant over incubation periods of 1 to 15 min, indicating that this reduction was not due to consumption of ATP. Since the spectrin and band-3 protein phosphorylations were specifically and identically reduced by casein and these reductions were not due to the ATP consumption or to a general alteration of the membrane, we conclude that the two substrates are likely phosphorylated by one kinase which also phosphorylates casein."}
{"id": "PMID:226709", "title": "Amino acid and 22Na+ uptake in membrane vesicles from confluent simian virus 40 transformed Balb/c3T3 and Balb/c3T3.", "content": "The studies reported here were carried out to characterize further previously described changes in membrane localized amino acid transport associated with simian virus 40 transformation of the mammalian cell line, Balb/c3T3. Membrane vesicles were prepared from confluent cultures of both simian virus 40 transformed Balb/c3T3 (SV3T3) and the untransformed parent line, Balb/c3T3 (3T3). An initial, externally imposed out greater than in, 100 mM a+ gradient produces acceleration of early ingress of alpha-aminoisobutyric acid (AlB) in vesicles from both cell lines, but transient, concentrative uptake (overshooting) only in SV3T3 vesicles. Early ingress of L-leucine is also accelerated in SV3T3 vesicles by a Na+ gradient, and overshooting is also demonstrable. Na+-gradient independent AIB permeability of SV3T3 and 3T3 membranes was estimated using uptake data, a first order rate equation and measurements of vesicle size derived from quasi-elastic light-scattering studies. AIB permeability of SV3T3 membranes is greater than that of 3T3 membranes (113 A/min and 43 A/min, respectively), suggesting that overshooting in 3T3 vesicles is not attenuated by a Na+-independent AIB \"leak\". Na+ permeability of the two membranes is similar, ruling out the possibility that a slower rate of Na+ equilibration across the SV3T3 membrane allows development of the overshoot. In SV3T3 vesicles the height of a Na+-gradient dependent overshoot varies with the initial [Na+]o/[Na+]i ratio, and ln[Na+]o/[Na+]i is linearly related to ln AIB uptake at overshoot peak/AIB uptake at equilibrium, consistent with the possibility that for [Na+]o/[Na+]i ratios in the range studied, AIB overshoot is energized by a constant proportion of the energy available from the initial electrochemical gradient for Na+. These results are consistent with the possibility that Na+-gradient dependent overshooting in SV3T3 vesicles is produced by Na+-amino acid carrier interactions resulting in either an increase in maximum transport velocity or an increase in carrier affinity for AIB.", "contents": "Amino acid and 22Na+ uptake in membrane vesicles from confluent simian virus 40 transformed Balb/c3T3 and Balb/c3T3. The studies reported here were carried out to characterize further previously described changes in membrane localized amino acid transport associated with simian virus 40 transformation of the mammalian cell line, Balb/c3T3. Membrane vesicles were prepared from confluent cultures of both simian virus 40 transformed Balb/c3T3 (SV3T3) and the untransformed parent line, Balb/c3T3 (3T3). An initial, externally imposed out greater than in, 100 mM a+ gradient produces acceleration of early ingress of alpha-aminoisobutyric acid (AlB) in vesicles from both cell lines, but transient, concentrative uptake (overshooting) only in SV3T3 vesicles. Early ingress of L-leucine is also accelerated in SV3T3 vesicles by a Na+ gradient, and overshooting is also demonstrable. Na+-gradient independent AIB permeability of SV3T3 and 3T3 membranes was estimated using uptake data, a first order rate equation and measurements of vesicle size derived from quasi-elastic light-scattering studies. AIB permeability of SV3T3 membranes is greater than that of 3T3 membranes (113 A/min and 43 A/min, respectively), suggesting that overshooting in 3T3 vesicles is not attenuated by a Na+-independent AIB \"leak\". Na+ permeability of the two membranes is similar, ruling out the possibility that a slower rate of Na+ equilibration across the SV3T3 membrane allows development of the overshoot. In SV3T3 vesicles the height of a Na+-gradient dependent overshoot varies with the initial [Na+]o/[Na+]i ratio, and ln[Na+]o/[Na+]i is linearly related to ln AIB uptake at overshoot peak/AIB uptake at equilibrium, consistent with the possibility that for [Na+]o/[Na+]i ratios in the range studied, AIB overshoot is energized by a constant proportion of the energy available from the initial electrochemical gradient for Na+. These results are consistent with the possibility that Na+-gradient dependent overshooting in SV3T3 vesicles is produced by Na+-amino acid carrier interactions resulting in either an increase in maximum transport velocity or an increase in carrier affinity for AIB."}
{"id": "PMID:226710", "title": "A mathematical model for membrane transport of amino acid and Na+ in vesicles.", "content": "A model with a carrier having sites for both amino acid and Na+ can account for AIB (alpha-aminoisobutyric acid) transport kinetics observed in membrane vesicles from SV3T3 (simian virus 40-tranformed Balb/c33 cells) and 3T3 (the parent cell line). The main feature of this cotransport model is that Na+ binding to carrier decreases the effective Km for AIB transport. Na+ transport kinetics observed in both vesicle systems can be described by passive (possibly facilitated) diffusion. The lag of Na+ transport across the membrane compared to that for AIB, coupled to the Na+-dependent decrease in the Km for AIB, accounts for the overshoot in intravesicular AIB observed for SV3T3 in the presence of an initial Na+ gradient. Extra-vesicular Na+ maintains a decrease in the Km for AIB influx before intra-vesicular Na+ has accumulated to balance it with a comparable decrease in the Km for AIB efflux. 3T3 vesicles display little overshoot, and this finding can be explained mostly by a lower carrier affinity for Na+.", "contents": "A mathematical model for membrane transport of amino acid and Na+ in vesicles. A model with a carrier having sites for both amino acid and Na+ can account for AIB (alpha-aminoisobutyric acid) transport kinetics observed in membrane vesicles from SV3T3 (simian virus 40-tranformed Balb/c33 cells) and 3T3 (the parent cell line). The main feature of this cotransport model is that Na+ binding to carrier decreases the effective Km for AIB transport. Na+ transport kinetics observed in both vesicle systems can be described by passive (possibly facilitated) diffusion. The lag of Na+ transport across the membrane compared to that for AIB, coupled to the Na+-dependent decrease in the Km for AIB, accounts for the overshoot in intravesicular AIB observed for SV3T3 in the presence of an initial Na+ gradient. Extra-vesicular Na+ maintains a decrease in the Km for AIB influx before intra-vesicular Na+ has accumulated to balance it with a comparable decrease in the Km for AIB efflux. 3T3 vesicles display little overshoot, and this finding can be explained mostly by a lower carrier affinity for Na+."}
{"id": "PMID:226711", "title": "Identification of differences between the surface proteins and glycoproteins of normal mouse (Balb/c) and human erythrocytes.", "content": "The topography of the external surface of the Balb/c mouse erythrocyte has been investigated and compared to the human erythrocyte by using a series of protein radiolabeling probes. After sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the pattern of Coomassie Blue stained proteins was very similar for mouse and human erythrocyte ghosts, as was the distribution of radioactivity in protein bands after lactoperoxidase catalyzed radioiodination. The mouse erythrocyte glycoproteins identified by periodic-acid-Schiff and 'Stains-All' reagents, sialic acid analysis of gel slices, binding of 125I-wheat germ agglutinin and 125I-concanavalin A to the gels, and glycoprotein radiolabeling techniques, differed markedly from the sets of proteins labeled by radioiodination, and also differed from the human erythrocyte glycoproteins. Instead of the PAS I to PAS IV series of sialoglycoproteins characteristic of human erythrocytes, the mouse erythrocyte possesses a broad band of sialoglycoproteins with several peaks ranging in mol wt from 65,000 to 32,000. The same group of sialoglycoproteins were labeled by the periodate/B3H4-technique specific for terminal sialic acid, and the galactose oxidase/B3H4-method (plus neuraminidase) specific for galactosyl/N-acetylgalactosaminyl residues penultimate to sialic acid. These results emphasize the necessity to employ a variety of protein radiolabeling probes based on different labeling specificities, to study the membrane topography of cells which are poorly understood compared to the human erythrocyte membrane.", "contents": "Identification of differences between the surface proteins and glycoproteins of normal mouse (Balb/c) and human erythrocytes. The topography of the external surface of the Balb/c mouse erythrocyte has been investigated and compared to the human erythrocyte by using a series of protein radiolabeling probes. After sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the pattern of Coomassie Blue stained proteins was very similar for mouse and human erythrocyte ghosts, as was the distribution of radioactivity in protein bands after lactoperoxidase catalyzed radioiodination. The mouse erythrocyte glycoproteins identified by periodic-acid-Schiff and 'Stains-All' reagents, sialic acid analysis of gel slices, binding of 125I-wheat germ agglutinin and 125I-concanavalin A to the gels, and glycoprotein radiolabeling techniques, differed markedly from the sets of proteins labeled by radioiodination, and also differed from the human erythrocyte glycoproteins. Instead of the PAS I to PAS IV series of sialoglycoproteins characteristic of human erythrocytes, the mouse erythrocyte possesses a broad band of sialoglycoproteins with several peaks ranging in mol wt from 65,000 to 32,000. The same group of sialoglycoproteins were labeled by the periodate/B3H4-technique specific for terminal sialic acid, and the galactose oxidase/B3H4-method (plus neuraminidase) specific for galactosyl/N-acetylgalactosaminyl residues penultimate to sialic acid. These results emphasize the necessity to employ a variety of protein radiolabeling probes based on different labeling specificities, to study the membrane topography of cells which are poorly understood compared to the human erythrocyte membrane."}
{"id": "PMID:226712", "title": "Further evidence for the existence of an intrinsic bicarbonate-stimulated Mg2+-ATPase in brush border membranes isolated from rat kidney cortex.", "content": "The aim of this study was to provide further evidence for the existence of a nonmitochondrial becarbonate-stimulated Mg2+-ATPase in brush border membranes derived from rat kidney cortex. A plasma membrane fraction rich in brush border microvilli and a mitochondrial fraction were isolated by differential centrifugation. Both fractions contain a Mg2+-ATPase activity which can be stimulated by bicarbonate. The two Mg2+-ATPases are stimulated likewise by chloride, bicarbonate, and sulfite or inhibited by oligomycin and aurovertin, though to different degrees. In contrast to these similarities, only the Mg2+-ATPase activity of the mitochondrial fraction is inhibited by atractyloside, a substance which blocks an adenine nucleotide translocator in the inner mitochondrial membrane. On the other hand, filipin, an antibiotic that complexes with cholesterol in the membranes inhibits exclusively the Mg2+-ATPase of the cholesterol-rich brush border membranes. Furthermore it could be demonstrated by the use of bromotetramisole, an inhibitor of alkaline phosphatase activity, that the Mg2+-ATPase activity in the membrane fraction is not due to the presence of the highly active alkaline phosphatase in these membranes. These results support the assumption that an intrinsic bicarbonate-stimulated Mg2+-ATPase is present in rat kidney brush border membranes.", "contents": "Further evidence for the existence of an intrinsic bicarbonate-stimulated Mg2+-ATPase in brush border membranes isolated from rat kidney cortex. The aim of this study was to provide further evidence for the existence of a nonmitochondrial becarbonate-stimulated Mg2+-ATPase in brush border membranes derived from rat kidney cortex. A plasma membrane fraction rich in brush border microvilli and a mitochondrial fraction were isolated by differential centrifugation. Both fractions contain a Mg2+-ATPase activity which can be stimulated by bicarbonate. The two Mg2+-ATPases are stimulated likewise by chloride, bicarbonate, and sulfite or inhibited by oligomycin and aurovertin, though to different degrees. In contrast to these similarities, only the Mg2+-ATPase activity of the mitochondrial fraction is inhibited by atractyloside, a substance which blocks an adenine nucleotide translocator in the inner mitochondrial membrane. On the other hand, filipin, an antibiotic that complexes with cholesterol in the membranes inhibits exclusively the Mg2+-ATPase of the cholesterol-rich brush border membranes. Furthermore it could be demonstrated by the use of bromotetramisole, an inhibitor of alkaline phosphatase activity, that the Mg2+-ATPase activity in the membrane fraction is not due to the presence of the highly active alkaline phosphatase in these membranes. These results support the assumption that an intrinsic bicarbonate-stimulated Mg2+-ATPase is present in rat kidney brush border membranes."}
{"id": "PMID:226713", "title": "Membrane pathways for water and solutes in the toad bladder: I. Independent activation of water and urea transport.", "content": "Vsopressin activates a number of transport systems in the toad bladder, including the systems for water, urea, sodium, and other small solutes. Evidence from experiments with selective inhibitors indicates that these transport systems are to a large extent functionally independent. In the present study, we show that the transport systems can be separately activated. Low concentrations of vasopressin (1 mU/ml) activate urea transport with virtually no effect on water transport. This selective effect is due in part to the relatively greater inhibitor action of endogenous prostaglandins on water transport. Low concentrations of 8-bromoadenosine cyclic AMP, on the other hand, activate water, but not urea transport. In additional experiments, we found that varying the ratio of exogenous cyclic AMP to theophylline activated water or urea transport selectively. These studies support the concept of independently controlled systems for water and solute transport, and provide a basis for the study of individual luminal membrane pathways for water and solutes in the accompanying paper.", "contents": "Membrane pathways for water and solutes in the toad bladder: I. Independent activation of water and urea transport. Vsopressin activates a number of transport systems in the toad bladder, including the systems for water, urea, sodium, and other small solutes. Evidence from experiments with selective inhibitors indicates that these transport systems are to a large extent functionally independent. In the present study, we show that the transport systems can be separately activated. Low concentrations of vasopressin (1 mU/ml) activate urea transport with virtually no effect on water transport. This selective effect is due in part to the relatively greater inhibitor action of endogenous prostaglandins on water transport. Low concentrations of 8-bromoadenosine cyclic AMP, on the other hand, activate water, but not urea transport. In additional experiments, we found that varying the ratio of exogenous cyclic AMP to theophylline activated water or urea transport selectively. These studies support the concept of independently controlled systems for water and solute transport, and provide a basis for the study of individual luminal membrane pathways for water and solutes in the accompanying paper."}
{"id": "PMID:226714", "title": "Membrane pathways for water and solutes in the toad bladder: II. Reflection coefficients of the water and solute channels.", "content": "Urea and water transport across the toad bladder can be separately activated by low concentrations of vasopressin or 8 Br-cAMP. Employing this method of selective activation, we have determined the reflection coefficient (sigma) of urea and other small molecules under circumstances in which the bladder was transporting urea or water. An osmotic method for the determination of sigma was used, in which the ability of a given solute to retard water efflux from the bladder was compared to that of raffinose (sigma = 1.0) or water (sigma = 0). When urea transport was activated (low concentration of vasopressin), sigma for urea and other solutes was low, (sigma urea, 0.08--0.39; sigma acetamide, 0.55; sigma ethylene glycol, 0.60). When water transport was activated (0.1 mM 8 Br-cAMP) sigma urea approached 1.0 sigma urea also approached 1.0 at high vasopressin concentrations. In a separate series of studies, sigma urea was determined in the presence of 2 x 10(-5) M KMnO4 in the luminal bathing medium. Under these conditions, when urea transport is selectively blocked, sigma urea rose from a value of 0.12 to 0.89. Thus, permanganate appears to \"close\" the urea transport channel. These findings indicate that the luminal membrane channels for water and solutes differ significantly in their dimensions. The solute channels, limited in number, have relatively large radii. They carry a small fraction (approximately 10%) of total water flow. The water transport channels, on the other hand, have small radii, approximately the size of a water molecule, and exclude solutes as small as urea.", "contents": "Membrane pathways for water and solutes in the toad bladder: II. Reflection coefficients of the water and solute channels. Urea and water transport across the toad bladder can be separately activated by low concentrations of vasopressin or 8 Br-cAMP. Employing this method of selective activation, we have determined the reflection coefficient (sigma) of urea and other small molecules under circumstances in which the bladder was transporting urea or water. An osmotic method for the determination of sigma was used, in which the ability of a given solute to retard water efflux from the bladder was compared to that of raffinose (sigma = 1.0) or water (sigma = 0). When urea transport was activated (low concentration of vasopressin), sigma for urea and other solutes was low, (sigma urea, 0.08--0.39; sigma acetamide, 0.55; sigma ethylene glycol, 0.60). When water transport was activated (0.1 mM 8 Br-cAMP) sigma urea approached 1.0 sigma urea also approached 1.0 at high vasopressin concentrations. In a separate series of studies, sigma urea was determined in the presence of 2 x 10(-5) M KMnO4 in the luminal bathing medium. Under these conditions, when urea transport is selectively blocked, sigma urea rose from a value of 0.12 to 0.89. Thus, permanganate appears to \"close\" the urea transport channel. These findings indicate that the luminal membrane channels for water and solutes differ significantly in their dimensions. The solute channels, limited in number, have relatively large radii. They carry a small fraction (approximately 10%) of total water flow. The water transport channels, on the other hand, have small radii, approximately the size of a water molecule, and exclude solutes as small as urea."}
{"id": "PMID:226715", "title": "Growth of short bones of the hand in children with Down's syndrome.", "content": "In this study, we report the elongation of the diaphyses of the short bones of the hand in an institutionalised sample of children with Down's syndrome. These diaphyses are significantly shorter than normal which is typical of other physical dimensions of individuals with Down's syndrome. Sex differences were generally lacking in diaphyseal lengths; this is in agreement with earlier reports. Pubescent spurts were not detected, but their absence cannot be certain. Roche (1965) reports the common absence of pubescent spurts in stature in children with Down's syndrome. However, only the magnitude of growth in stature of a small sample of these Down's children differed from normal; this dissimilarity was the result of differences in adult statures of normal and Down's individuals (Rarick, Wainer, Thissen and Seefeldt, 1975). Benda (1960) speculates that growth of the short bones of the hand stops early; thus, the pubescent spurt may be prevented by premature, epiphyseal closure. This would be in partial agreement with reports for stature (Roche, 1965). In this sample of children with Down's syndrome the extra chromosome, No. 21, appears to affect the growth of short bones of the hand before seven years of age. The diaphyses of short bones of the hand in these children are shorter than normal by seven years of age and significantly so after eleven years of age; but thereafter, these bones grow normally except for the absence of a pubescent spurt. This pattern is similar to reports of growth in length of other parts of the skeleton in children with Down's syndrome.", "contents": "Growth of short bones of the hand in children with Down's syndrome. In this study, we report the elongation of the diaphyses of the short bones of the hand in an institutionalised sample of children with Down's syndrome. These diaphyses are significantly shorter than normal which is typical of other physical dimensions of individuals with Down's syndrome. Sex differences were generally lacking in diaphyseal lengths; this is in agreement with earlier reports. Pubescent spurts were not detected, but their absence cannot be certain. Roche (1965) reports the common absence of pubescent spurts in stature in children with Down's syndrome. However, only the magnitude of growth in stature of a small sample of these Down's children differed from normal; this dissimilarity was the result of differences in adult statures of normal and Down's individuals (Rarick, Wainer, Thissen and Seefeldt, 1975). Benda (1960) speculates that growth of the short bones of the hand stops early; thus, the pubescent spurt may be prevented by premature, epiphyseal closure. This would be in partial agreement with reports for stature (Roche, 1965). In this sample of children with Down's syndrome the extra chromosome, No. 21, appears to affect the growth of short bones of the hand before seven years of age. The diaphyses of short bones of the hand in these children are shorter than normal by seven years of age and significantly so after eleven years of age; but thereafter, these bones grow normally except for the absence of a pubescent spurt. This pattern is similar to reports of growth in length of other parts of the skeleton in children with Down's syndrome."}
{"id": "PMID:226723", "title": "Long-term survival in a case of stage IV carcinoma of the ovary treated with a single chemotherapeutic agent.", "content": "A case of stage IV carcinoma of the ovary is presented which was treated approximately six years ago in the Department of Radiation Therapy at Queens Hospital Center. On September 12, 1972, the patient had a total abdominal hysterectomy and bilateral salpingo-oophorectomy for a papillary scirrhous cystadenocarcinoma of the left ovary. At the time of the operation, the patient was found to have stage IV carcinoma of the ovary due to metastases of the liver and rectum. She was scheduled to receive pelvic-abdominal postoperative radiation therapy via the moving strip technique. Unfortunately, after completion of two strips, the patient could not tolerate treatment. She then began chemotherapy with a single agent, chlorambucil.Chlorambucil, 0.2 mg/kg/day\u00d725 days/course was administered. The patient received 18 courses. Treatment dosage on a few occasions was decreased and increased again, due to drops in hemoglobin level and white blood cell and platelet counts. At the time of this presentation, the patient has no signs or symptoms of the disease. The introduction of megavoltage radiotherapy and adjuvant chemotherapy postoperatively has significantly improved the prognosis for patients with ovarian carcinoma. However, despite progress in radiotherapy, some patients cannot sustain this kind of treatment due to the unwanted side effects. Such was the case in this patient. She was switched to chemotherapy with excellent results in response and survival, even cure.", "contents": "Long-term survival in a case of stage IV carcinoma of the ovary treated with a single chemotherapeutic agent. A case of stage IV carcinoma of the ovary is presented which was treated approximately six years ago in the Department of Radiation Therapy at Queens Hospital Center. On September 12, 1972, the patient had a total abdominal hysterectomy and bilateral salpingo-oophorectomy for a papillary scirrhous cystadenocarcinoma of the left ovary. At the time of the operation, the patient was found to have stage IV carcinoma of the ovary due to metastases of the liver and rectum. She was scheduled to receive pelvic-abdominal postoperative radiation therapy via the moving strip technique. Unfortunately, after completion of two strips, the patient could not tolerate treatment. She then began chemotherapy with a single agent, chlorambucil.Chlorambucil, 0.2 mg/kg/day\u00d725 days/course was administered. The patient received 18 courses. Treatment dosage on a few occasions was decreased and increased again, due to drops in hemoglobin level and white blood cell and platelet counts. At the time of this presentation, the patient has no signs or symptoms of the disease. The introduction of megavoltage radiotherapy and adjuvant chemotherapy postoperatively has significantly improved the prognosis for patients with ovarian carcinoma. However, despite progress in radiotherapy, some patients cannot sustain this kind of treatment due to the unwanted side effects. Such was the case in this patient. She was switched to chemotherapy with excellent results in response and survival, even cure."}
{"id": "PMID:226725", "title": "Therapeutic trial of four amoebicide regimes in rural Zaire.", "content": "A prospective comparative trial of four amoebicide regimes was carried out with protozoological control using 300 patients presenting with symptomatic intestinal amoebiasis at a tropical rural hospital during a five month period. 195 (76.2%) of 256 treated supplied three follow-up stools. Of those treated with Metronidazole and Oxytetracycline 10.9 per cent continued to excrete Entamoeba histolytica while with Di-iodohydroxyquinoline and Oxytetracycline the figure was 25.5 per cent falling to 20.0 per cent when Dehydroemetine was added and with Clioquinol and Oxytetracycline 27.5 per cent continued to excrete Entamoeba histolytica. These figures with the absolute numbers of patients involved do not show any one of the regimes used to be significantly more effective than the others in unclassified symptomatic intestinal amoebiasis. We conclude therefore that in the rural situation the cheapest regime should be preferred as the standard one, namely Clioquinol and Oxytetracycline. However, in view of the reported serious side-effects of Clioquinol, Di-iodomydroxyquinoline and Oxytetracycline could be considered as the second cheapest and with slightly better results.", "contents": "Therapeutic trial of four amoebicide regimes in rural Zaire. A prospective comparative trial of four amoebicide regimes was carried out with protozoological control using 300 patients presenting with symptomatic intestinal amoebiasis at a tropical rural hospital during a five month period. 195 (76.2%) of 256 treated supplied three follow-up stools. Of those treated with Metronidazole and Oxytetracycline 10.9 per cent continued to excrete Entamoeba histolytica while with Di-iodohydroxyquinoline and Oxytetracycline the figure was 25.5 per cent falling to 20.0 per cent when Dehydroemetine was added and with Clioquinol and Oxytetracycline 27.5 per cent continued to excrete Entamoeba histolytica. These figures with the absolute numbers of patients involved do not show any one of the regimes used to be significantly more effective than the others in unclassified symptomatic intestinal amoebiasis. We conclude therefore that in the rural situation the cheapest regime should be preferred as the standard one, namely Clioquinol and Oxytetracycline. However, in view of the reported serious side-effects of Clioquinol, Di-iodomydroxyquinoline and Oxytetracycline could be considered as the second cheapest and with slightly better results."}
{"id": "PMID:226730", "title": "Brain metastases in small cell carcinoma of the lung.", "content": "The records of 177 patients with small cell carcinoma of the lung were reviewed to determine parameters associated with brain metastases. Complete autopsy, including examination of the brain, was done in each case. Of the 70 cases of brain metastases, only two patients (3%) were aged 70 years or more as compared with 19 (18%) aged 70 years or more who did not have brain metastases. Patients with brain metastases had a longer median survival as compared with those without brain metastases. Patients with brain metastases had involvement of the thyroid and kidney more frequently (23% and 34%, respectively) compared with patients without brain metastases (8% and 13%). Thus, patients who have brain metastases tend to (1) be less than 70 years of age; (2) have a longer survival; and (3) have a higher incidence of metastases to the thyroid and kidney.", "contents": "Brain metastases in small cell carcinoma of the lung. The records of 177 patients with small cell carcinoma of the lung were reviewed to determine parameters associated with brain metastases. Complete autopsy, including examination of the brain, was done in each case. Of the 70 cases of brain metastases, only two patients (3%) were aged 70 years or more as compared with 19 (18%) aged 70 years or more who did not have brain metastases. Patients with brain metastases had a longer median survival as compared with those without brain metastases. Patients with brain metastases had involvement of the thyroid and kidney more frequently (23% and 34%, respectively) compared with patients without brain metastases (8% and 13%). Thus, patients who have brain metastases tend to (1) be less than 70 years of age; (2) have a longer survival; and (3) have a higher incidence of metastases to the thyroid and kidney."}
{"id": "PMID:226732", "title": "High-density lipoprotein-cholesterol in survivors of myocardial infarction.", "content": "High-density lipoprotein-cholesterol (HDL-Chol) levels were higher in a group of 83 myocardial infarction survivors who participated in a moderate, graded exercise program (47 +/- 13 mg/dL) than in 103 nonexercising coronary heart disease patients (40 +/- 11 mg/dL, P less than .001), reaching levels undistinguishable from those of 181 population controls (44 +/- 12 mg/dL). The level of exercise and concentration of HDL-Chol were correlated (r = .24, P less than .05). In 18 patients studied longitudinally, HDL-Chol levels increased from 35 +/- 8 mg/dL before participation to 40 mg/dL (P less than .001) after one week, and remained at that level for six months. Concurrently, functional aerobic impairment decreased from 31% +/- 29% to 11% (P less than .01). These observations suggest that participation in a moderate exercise program increases HDL-Chol levels in myocardial infarction survivors and may contribute to lowering the risk for subsequent infarction.", "contents": "High-density lipoprotein-cholesterol in survivors of myocardial infarction. High-density lipoprotein-cholesterol (HDL-Chol) levels were higher in a group of 83 myocardial infarction survivors who participated in a moderate, graded exercise program (47 +/- 13 mg/dL) than in 103 nonexercising coronary heart disease patients (40 +/- 11 mg/dL, P less than .001), reaching levels undistinguishable from those of 181 population controls (44 +/- 12 mg/dL). The level of exercise and concentration of HDL-Chol were correlated (r = .24, P less than .05). In 18 patients studied longitudinally, HDL-Chol levels increased from 35 +/- 8 mg/dL before participation to 40 mg/dL (P less than .001) after one week, and remained at that level for six months. Concurrently, functional aerobic impairment decreased from 31% +/- 29% to 11% (P less than .01). These observations suggest that participation in a moderate exercise program increases HDL-Chol levels in myocardial infarction survivors and may contribute to lowering the risk for subsequent infarction."}
{"id": "PMID:226733", "title": "Moderate exercise and high-density lipoprotein-cholesterol. Observations during a cardiac rehabilitation program.", "content": "The effects of a 13-week moderate exercise program on fasting plasma insulin, lipids, and lipoprotein cholesterol concentrations were studied in 32 sedentary, middle-aged men with coronary artery disease. The preponderant component of the exercise program was walking or slow jogging. There was no significant change in the systolic blood pressure and pulse rate product response to a standard exercise load. The high-density lipoprotein-cholesterol (HDL-C) level increased, and the fasting plasma insulin concentration decreased. There were no significant changes in plasma triglycerides or low-density lipoprotein cholesterol levels. In sedentary subjects with coronary artery disease, a modest increase in activity can result in an increase in the HDL-C level and a decrease in the plasma insulin concentration. These changes occurred in the absence of variations in diet, smoking habits, adiposity, or plasma triglyceride concentrations and did not require a cardiovascular training effect.", "contents": "Moderate exercise and high-density lipoprotein-cholesterol. Observations during a cardiac rehabilitation program. The effects of a 13-week moderate exercise program on fasting plasma insulin, lipids, and lipoprotein cholesterol concentrations were studied in 32 sedentary, middle-aged men with coronary artery disease. The preponderant component of the exercise program was walking or slow jogging. There was no significant change in the systolic blood pressure and pulse rate product response to a standard exercise load. The high-density lipoprotein-cholesterol (HDL-C) level increased, and the fasting plasma insulin concentration decreased. There were no significant changes in plasma triglycerides or low-density lipoprotein cholesterol levels. In sedentary subjects with coronary artery disease, a modest increase in activity can result in an increase in the HDL-C level and a decrease in the plasma insulin concentration. These changes occurred in the absence of variations in diet, smoking habits, adiposity, or plasma triglyceride concentrations and did not require a cardiovascular training effect."}
{"id": "PMID:226735", "title": "Effects of estrogens on sleep and psychological state of hypogonadal women.", "content": "A double-lind crossover study involving 16 hypogonadal women compared the effects of placebo and conjugated estrogens, 0.625 mg daily, on gonadotropin levels, symptoms, sleep patterns, and psychological state. After one month, serum concentrations of follicle-stimulating hormone fell 31%, and levels of luteinizing hormone, 19%; the number of vasomotor flushes also decreased. The administration of estrogens was also associated with a shorter mean sleep latency, a longer period of rapid eye movement sleep, and a positive correlation between psychological intactness (as clinically ranked) and latency to sleep onset. Psychological testing, including the Clyde Mood Scale, and the Gottschalk-Gleser Test indicated that estrogens caused this group to be less outwardly aggressive but more inwardly hostile.", "contents": "Effects of estrogens on sleep and psychological state of hypogonadal women. A double-lind crossover study involving 16 hypogonadal women compared the effects of placebo and conjugated estrogens, 0.625 mg daily, on gonadotropin levels, symptoms, sleep patterns, and psychological state. After one month, serum concentrations of follicle-stimulating hormone fell 31%, and levels of luteinizing hormone, 19%; the number of vasomotor flushes also decreased. The administration of estrogens was also associated with a shorter mean sleep latency, a longer period of rapid eye movement sleep, and a positive correlation between psychological intactness (as clinically ranked) and latency to sleep onset. Psychological testing, including the Clyde Mood Scale, and the Gottschalk-Gleser Test indicated that estrogens caused this group to be less outwardly aggressive but more inwardly hostile."}
{"id": "PMID:226760", "title": "Giant cell formation in the brain of suckling mice infected with mouse hepatitis virus, JHM strain.", "content": "After intranasal inoculation with a neurotropic mouse hepatitis virus, JHM strain, suckling mice less than 2 weeks of age died in 4 or 5 days postinoculation, while those 3 weeks or more of age survived. In the brain lesions of mice 8 days or less of age, there appeared two different types of multinucleated giant cells. One of them which was irregular in shape with many virus particles, appeared mostly in the subependymal or perivascular areas after 72 h postinoculation and it seemed to have resulted from a fusion of two or more infected macrophages. The other type of giant cells which was oval in shape with a small number of virus particles, appeared within degenerative lesions at 96 h postinoculation. It consisted of two morphologically different parts and seemed to be a complex of infected neurons and reacting macrophages. In the cerebral lesions of mice 2 to 4 weeks of age, only the former type of giant cells appeared.", "contents": "Giant cell formation in the brain of suckling mice infected with mouse hepatitis virus, JHM strain. After intranasal inoculation with a neurotropic mouse hepatitis virus, JHM strain, suckling mice less than 2 weeks of age died in 4 or 5 days postinoculation, while those 3 weeks or more of age survived. In the brain lesions of mice 8 days or less of age, there appeared two different types of multinucleated giant cells. One of them which was irregular in shape with many virus particles, appeared mostly in the subependymal or perivascular areas after 72 h postinoculation and it seemed to have resulted from a fusion of two or more infected macrophages. The other type of giant cells which was oval in shape with a small number of virus particles, appeared within degenerative lesions at 96 h postinoculation. It consisted of two morphologically different parts and seemed to be a complex of infected neurons and reacting macrophages. In the cerebral lesions of mice 2 to 4 weeks of age, only the former type of giant cells appeared."}
{"id": "PMID:226764", "title": "[Effects of orciprenaline on the responses to Ca, K, acetylcholine and Ba in the isolated seminal vesicles of guinea pigs, especially in relation to cyclic AMP (author's transl)].", "content": "By using the isolated seminal vesicles of guinea pigs, the effects of dibutyryl cyclic AMP and beta-stimulant, orciprenaline, on the responses to Ca, K, acetylcholine and Ba were investigated, especially in relation to cyclic AMP. The following results were obtained. 1. Orciprenaline inhibited the contraction produced by Ca, K, acetylcholine and Ba in a dose-dependent manner, and the inhibition became larger in the order of Ca, K, acetylcholine and Ba. 2. Dibutyryl cyclic AMP showed the same results as those of orciprenaline. That is, dibutyryl cyclic AMP inhibited the contractions produced by acetylcholine and Ba. 3. Orciprenaline showed the increased level of cyclic AMP in a dose-dependent manner. But the increase was not remarkable in the concentration in which the contractions produced by the tested contractile agents were inhibited by about 50%. From these results, the following suggestions were obtained; (1) there exists beta-receptor in guinea pig seminal vesicles and (2) a part of actions of orciprenaline is due to a mechanism unrelated to cyclic AMP.", "contents": "[Effects of orciprenaline on the responses to Ca, K, acetylcholine and Ba in the isolated seminal vesicles of guinea pigs, especially in relation to cyclic AMP (author's transl)]. By using the isolated seminal vesicles of guinea pigs, the effects of dibutyryl cyclic AMP and beta-stimulant, orciprenaline, on the responses to Ca, K, acetylcholine and Ba were investigated, especially in relation to cyclic AMP. The following results were obtained. 1. Orciprenaline inhibited the contraction produced by Ca, K, acetylcholine and Ba in a dose-dependent manner, and the inhibition became larger in the order of Ca, K, acetylcholine and Ba. 2. Dibutyryl cyclic AMP showed the same results as those of orciprenaline. That is, dibutyryl cyclic AMP inhibited the contractions produced by acetylcholine and Ba. 3. Orciprenaline showed the increased level of cyclic AMP in a dose-dependent manner. But the increase was not remarkable in the concentration in which the contractions produced by the tested contractile agents were inhibited by about 50%. From these results, the following suggestions were obtained; (1) there exists beta-receptor in guinea pig seminal vesicles and (2) a part of actions of orciprenaline is due to a mechanism unrelated to cyclic AMP."}
{"id": "PMID:226765", "title": "[Study of the effect of various intermediate products and enzymes of carbohydrate metabolism on erythrocyte aggregation].", "content": "The effect of some substances on the aggregation of red blood cells induced by gamma-globulin and fibrinogen was studied in vitro. Fructose 1,6-diphosphate, glucose 6-phosphate, glyceraldehyde dehydrogenase, insulin and prostaglandin E1 inhibited aggregation of red cells. Glucose, glucose 1,6-phosphate and ACTH had different effects in various concentrations on red cell aggregation, while fructose, prednisolon and D-oxy-prostaglandin E1 alpha and E1 beta caused no effect.", "contents": "[Study of the effect of various intermediate products and enzymes of carbohydrate metabolism on erythrocyte aggregation]. The effect of some substances on the aggregation of red blood cells induced by gamma-globulin and fibrinogen was studied in vitro. Fructose 1,6-diphosphate, glucose 6-phosphate, glyceraldehyde dehydrogenase, insulin and prostaglandin E1 inhibited aggregation of red cells. Glucose, glucose 1,6-phosphate and ACTH had different effects in various concentrations on red cell aggregation, while fructose, prednisolon and D-oxy-prostaglandin E1 alpha and E1 beta caused no effect."}
{"id": "PMID:226766", "title": "[Comparative analysis of incidence of main risk factors, behavior characteristics and work activity in ischemic heart disease with normolipemia and hyperlipoproteinemia type II and IV].", "content": "Examination was conducted of 180 healthy males 35 to 44 years of age, working as leading engineers, and of 174 patients with ischemic heart disease selected according to sex and occupation. A comparative analysis was made of the frequency of the main risk factors and some peculiarities of the labour activity and behaviour of patients with types II and IV hyperlipoproteinemia and those with normal lipid level. It is shown that a combination of known risk factors, behaviour peculiarities and conditions of labour activity is typical of patients with type IV hyperlipoproteinemia, which may promote the development of ischemic heart disease. Patients with normal blood lipid livel merit special attention. Additional factors contributing to the development of ischemic heart disease in these cases should be searched for.", "contents": "[Comparative analysis of incidence of main risk factors, behavior characteristics and work activity in ischemic heart disease with normolipemia and hyperlipoproteinemia type II and IV]. Examination was conducted of 180 healthy males 35 to 44 years of age, working as leading engineers, and of 174 patients with ischemic heart disease selected according to sex and occupation. A comparative analysis was made of the frequency of the main risk factors and some peculiarities of the labour activity and behaviour of patients with types II and IV hyperlipoproteinemia and those with normal lipid level. It is shown that a combination of known risk factors, behaviour peculiarities and conditions of labour activity is typical of patients with type IV hyperlipoproteinemia, which may promote the development of ischemic heart disease. Patients with normal blood lipid livel merit special attention. Additional factors contributing to the development of ischemic heart disease in these cases should be searched for."}
{"id": "PMID:226767", "title": "[Myocardial scintigraphy with pyrophosphate-99mTc in transitory myocardial ischemia in chronic ischemic heart disease].", "content": "Scintigraphy of the myocardium with pyrophosphate-99mTc was used in the examination of 45 patients with chronic ischemic heart disease and 3 patients with vegetovascular dystonia. A direct dependence of the character of the scintigram on the anginous attack was revealed. Accumulation of pyrophosphate-99mTc in the myocardium was observed in all patients with the agent injected just before the attack, during the attack or in the first 8 hours after it. Pyrophosphate-99mTc accumulation in the myocardium demonstrated on the scintigrams of the myocardium was less intense but more diffuse and extensive in chronic ischemic heart disease than in the focus of acute myocardial infarction.", "contents": "[Myocardial scintigraphy with pyrophosphate-99mTc in transitory myocardial ischemia in chronic ischemic heart disease]. Scintigraphy of the myocardium with pyrophosphate-99mTc was used in the examination of 45 patients with chronic ischemic heart disease and 3 patients with vegetovascular dystonia. A direct dependence of the character of the scintigram on the anginous attack was revealed. Accumulation of pyrophosphate-99mTc in the myocardium was observed in all patients with the agent injected just before the attack, during the attack or in the first 8 hours after it. Pyrophosphate-99mTc accumulation in the myocardium demonstrated on the scintigrams of the myocardium was less intense but more diffuse and extensive in chronic ischemic heart disease than in the focus of acute myocardial infarction."}
{"id": "PMID:226768", "title": "Effect of indomethacin and adrenocorticotrophic hormone on renal function in man: an experimental model of inappropriate antidiuresis.", "content": "The effect of prostaglandin synthesis inhibition on basal and ACTH-stimulated adrenal and renal function was investigated in normal volunteers. Data were collected during control and experimental study periods (13 days each). Adrenocorticotrophic hormone (Cosyntropin, 80 U/day) was administered i.v. on days 8 and 9 of each period. Indomethacin (150 mg/day) was given on days 5 through 13 of the experimental period. The subjects ate a constant diet containing 9 mEq of sodium, 100 mEq of potassium, and 2,500 ml of fluid daily. Indomethacin markedly inhibited urinary PGE excretion and plasma PGE concentration. The effect of ACTH alone as compared to the effect of ACTH and indomethacin showed: plasma sodium concentration, 139 +/- 1 vs. 131 +/ 3 mEg/liter (P less than 0.01, mean +/- SEM); plasma osmolality, 287 +/- 3 vs. 270 +/- 3 mOsm/liter (P less than 0.01); free water clearance, 97 +/- 66 vs. -1100 +/- 380 ml/24hr (P less than 0.01); urine volume, 2,000 +/- 60 vs. 950 +/- 200 ml/day (P less than 0.01); and urine osmolality 282 +/- 12 vs. 720 +/- 144 mOsm/liter (P less than 0.01). We conclude that the effects of ACTH and prostaglandin synthesis inhibition interact to result in inappropriate antidiuresis.", "contents": "Effect of indomethacin and adrenocorticotrophic hormone on renal function in man: an experimental model of inappropriate antidiuresis. The effect of prostaglandin synthesis inhibition on basal and ACTH-stimulated adrenal and renal function was investigated in normal volunteers. Data were collected during control and experimental study periods (13 days each). Adrenocorticotrophic hormone (Cosyntropin, 80 U/day) was administered i.v. on days 8 and 9 of each period. Indomethacin (150 mg/day) was given on days 5 through 13 of the experimental period. The subjects ate a constant diet containing 9 mEq of sodium, 100 mEq of potassium, and 2,500 ml of fluid daily. Indomethacin markedly inhibited urinary PGE excretion and plasma PGE concentration. The effect of ACTH alone as compared to the effect of ACTH and indomethacin showed: plasma sodium concentration, 139 +/- 1 vs. 131 +/ 3 mEg/liter (P less than 0.01, mean +/- SEM); plasma osmolality, 287 +/- 3 vs. 270 +/- 3 mOsm/liter (P less than 0.01); free water clearance, 97 +/- 66 vs. -1100 +/- 380 ml/24hr (P less than 0.01); urine volume, 2,000 +/- 60 vs. 950 +/- 200 ml/day (P less than 0.01); and urine osmolality 282 +/- 12 vs. 720 +/- 144 mOsm/liter (P less than 0.01). We conclude that the effects of ACTH and prostaglandin synthesis inhibition interact to result in inappropriate antidiuresis."}
{"id": "PMID:226769", "title": "[Glomangioma in the eyelid. A clinical and histological case report (author's transl)].", "content": "A glomangioma of the eyelid is presented. This localisation of such a tumor is considered to be an extremely exceptional one. Clinical and histological details are described. The differential diagnosis is discussed.", "contents": "[Glomangioma in the eyelid. A clinical and histological case report (author's transl)]. A glomangioma of the eyelid is presented. This localisation of such a tumor is considered to be an extremely exceptional one. Clinical and histological details are described. The differential diagnosis is discussed."}
{"id": "PMID:226805", "title": "Lipid-protein interactions in membranes: effect of lipid composition on mobility of spin-labeled cysteine residues in yeast plasma membrane.", "content": "In order to gain direct evidence for lipid-dependent protein conformation in membrane, effects of modification of lipid composition on mobility of spin-labeled cysteine residues were investigated in the plasma membrane of the yeast Saccharomyces cerevisiae. Conversion of the bulk of phospholipids to diglycerides by treatment of the membrane with phospholipase C substantially enhanced spectral anisotropy. However, alterations of the viscosity of the lipid-bilayer by enriching the membrane with palmitelaidic or oleic acid had no effect on mobility of spin-labeled cysteine residues. These observations indicate that while the spin-labeled residues are not in direct contact with the lipid core of the membrane, there are lipid-protein interactions to the extent that removal of the polar portion of the bulk of phospholipids induces conformational changes in proteins, which in turn restrict mobility of these residues. It is concluded that conformation of membrane proteins on lipid structure and that phospholipids have a role in preserving the native conformation of proteins.", "contents": "Lipid-protein interactions in membranes: effect of lipid composition on mobility of spin-labeled cysteine residues in yeast plasma membrane. In order to gain direct evidence for lipid-dependent protein conformation in membrane, effects of modification of lipid composition on mobility of spin-labeled cysteine residues were investigated in the plasma membrane of the yeast Saccharomyces cerevisiae. Conversion of the bulk of phospholipids to diglycerides by treatment of the membrane with phospholipase C substantially enhanced spectral anisotropy. However, alterations of the viscosity of the lipid-bilayer by enriching the membrane with palmitelaidic or oleic acid had no effect on mobility of spin-labeled cysteine residues. These observations indicate that while the spin-labeled residues are not in direct contact with the lipid core of the membrane, there are lipid-protein interactions to the extent that removal of the polar portion of the bulk of phospholipids induces conformational changes in proteins, which in turn restrict mobility of these residues. It is concluded that conformation of membrane proteins on lipid structure and that phospholipids have a role in preserving the native conformation of proteins."}
{"id": "PMID:226806", "title": "Malignant fibrous histiocytoma arising in a patient with multiple neurofibromatosis: a case report and a literature review.", "content": "A case report of a 56-year-old man with the characteristic clinical and histologic features of multiple neurofibromatosis is presented. This patient was also diagnosed as having a malignant fibrous histiocytoma involving the right thigh with metastasis to the lung. A definite association between Von Recklinghausen's disease and various sarcomas (most commonly neurofibrosarcomas) of the peripheral nerves and the somatic soft tissues is well-known. This is apparently the first report in the literature of a malignant fibrous histiocytoma arising in a patient with multiple neurofibromatosis. The phenomenon of sarcomatous change in Von Recklinghausen's disease and the clinical and pathologic features of malignant fibrous histiocytoma are also discussed.", "contents": "Malignant fibrous histiocytoma arising in a patient with multiple neurofibromatosis: a case report and a literature review. A case report of a 56-year-old man with the characteristic clinical and histologic features of multiple neurofibromatosis is presented. This patient was also diagnosed as having a malignant fibrous histiocytoma involving the right thigh with metastasis to the lung. A definite association between Von Recklinghausen's disease and various sarcomas (most commonly neurofibrosarcomas) of the peripheral nerves and the somatic soft tissues is well-known. This is apparently the first report in the literature of a malignant fibrous histiocytoma arising in a patient with multiple neurofibromatosis. The phenomenon of sarcomatous change in Von Recklinghausen's disease and the clinical and pathologic features of malignant fibrous histiocytoma are also discussed."}
{"id": "PMID:226807", "title": "Experimental opacification of mediastinal lymph nodes by intraperitoneal injection of an iodinated fatty emulsion.", "content": "Absorption and lymphatic drainage of several lipiodol emulsions injected intraperitoneally have been studied in the rabbit and rat. Good opacification of the lymphatic channels and mediastinal lymph nodes is obtained in several hours with fine emulsions and in several days with coarse emulsions. The tolerance is related to dose, and the peritoneal reaction was moderate with the low doses, similar to that caused by the administration of physiologic saline alone. Computerized tomography in detecting low contrasts attained with small doses could render this method of indirect lymphography possible in man.", "contents": "Experimental opacification of mediastinal lymph nodes by intraperitoneal injection of an iodinated fatty emulsion. Absorption and lymphatic drainage of several lipiodol emulsions injected intraperitoneally have been studied in the rabbit and rat. Good opacification of the lymphatic channels and mediastinal lymph nodes is obtained in several hours with fine emulsions and in several days with coarse emulsions. The tolerance is related to dose, and the peritoneal reaction was moderate with the low doses, similar to that caused by the administration of physiologic saline alone. Computerized tomography in detecting low contrasts attained with small doses could render this method of indirect lymphography possible in man."}
{"id": "PMID:226809", "title": "5-HT induced accumulation of 3',5'-AMP and the phosphorylation of paramyosin in the ABRM of Mytilus edulis.", "content": "In Mytilus edulis 5-Ht induced relaxation of a muscle in catch is preceded by an increase in 3',5'-AMP content. In vitro two proteins of the contractile apparatus are phosphorylated by 3',5'-AMP dependent protein kinases. The 295000 dalton protein cannot be identified, the other one is paramyosin. Phosphorylated paramyosin inhibits actomyosin ATPase of smooth mollusc muscles at low and high Ca++ concentrations.", "contents": "5-HT induced accumulation of 3',5'-AMP and the phosphorylation of paramyosin in the ABRM of Mytilus edulis. In Mytilus edulis 5-Ht induced relaxation of a muscle in catch is preceded by an increase in 3',5'-AMP content. In vitro two proteins of the contractile apparatus are phosphorylated by 3',5'-AMP dependent protein kinases. The 295000 dalton protein cannot be identified, the other one is paramyosin. Phosphorylated paramyosin inhibits actomyosin ATPase of smooth mollusc muscles at low and high Ca++ concentrations."}
{"id": "PMID:226810", "title": "The re-formation of connections in the nervous sytem of Lymnaea stagnalis after nerve injury.", "content": "Changes in the tentacle reflex pathway of the pond snail Lymnaea stagnalis induced by peripheral nerve injury were studied with behavioural and electrophysiological techniques. After nerve injury regeneration of sensory axons is obtained in 6-12 days, suggesting an axonal outgrowth at a rate of 1 mm per day. Recovery of the tentacle reflex takes much more time indicating that synaptic efficacy is affected considerably by the period of sensory deprivation following nerve injury.", "contents": "The re-formation of connections in the nervous sytem of Lymnaea stagnalis after nerve injury. Changes in the tentacle reflex pathway of the pond snail Lymnaea stagnalis induced by peripheral nerve injury were studied with behavioural and electrophysiological techniques. After nerve injury regeneration of sensory axons is obtained in 6-12 days, suggesting an axonal outgrowth at a rate of 1 mm per day. Recovery of the tentacle reflex takes much more time indicating that synaptic efficacy is affected considerably by the period of sensory deprivation following nerve injury."}
{"id": "PMID:226811", "title": "Functional characteristics of an identified pair of neurones in the CNS of the pond snail (Lymnaea stagnalis L.).", "content": "The properties of 2 giant electrically coupled neurones (A10 and P1) identified in the visceral and right parietal ganglia of Lymnaea stagnalis were examined. The active and passive electrical parameters of the neurones, as well as the junction between them were measured. The main peripheral and interneuronal connections of the neurones were demonstrated using both electrophysiological and morphological methods. It is shown that the coupled cells are not neurones of the same function, but they are asymmetrical ones. This finding is supported by the following results: (1) the axonal pathways of neurones A10 and P1 are different; (2) there are significant differences in their afferent and efferent connections; (3) though the electrical junction between them is bidirectional, the junctional electrical characteristics prefer P1-A10 transmission. According to the electron microscopic results both neurones are possible neurosecretory cells. The differences demonstrated between the 2 giant neurones may have significance concerning their role in a special neuronal network.", "contents": "Functional characteristics of an identified pair of neurones in the CNS of the pond snail (Lymnaea stagnalis L.). The properties of 2 giant electrically coupled neurones (A10 and P1) identified in the visceral and right parietal ganglia of Lymnaea stagnalis were examined. The active and passive electrical parameters of the neurones, as well as the junction between them were measured. The main peripheral and interneuronal connections of the neurones were demonstrated using both electrophysiological and morphological methods. It is shown that the coupled cells are not neurones of the same function, but they are asymmetrical ones. This finding is supported by the following results: (1) the axonal pathways of neurones A10 and P1 are different; (2) there are significant differences in their afferent and efferent connections; (3) though the electrical junction between them is bidirectional, the junctional electrical characteristics prefer P1-A10 transmission. According to the electron microscopic results both neurones are possible neurosecretory cells. The differences demonstrated between the 2 giant neurones may have significance concerning their role in a special neuronal network."}
{"id": "PMID:226815", "title": "Receptors for insulin and epidermal growth factor-urogastrone in adult human fibroblasts do not change with donor age.", "content": "The ligand binding and biological responsiveness of cultured fibroblast monolayers were measured for porcine insulin and for murine epidermal growth factor--urogastrone in skin fibroblast cultures derived from young (22 to 31 years) and old (65 to 80 years) normal male volunteer donors. The receptor characteristics of the cells studied from the two groups of donors were not found to differ. In contrast with previous data, suggesting that there may be a genetically programmed aging of the insulin binding system, it is concluded that for both insulin and epidermal growth factor, receptor characteristics do not change with adult donor age.", "contents": "Receptors for insulin and epidermal growth factor-urogastrone in adult human fibroblasts do not change with donor age. The ligand binding and biological responsiveness of cultured fibroblast monolayers were measured for porcine insulin and for murine epidermal growth factor--urogastrone in skin fibroblast cultures derived from young (22 to 31 years) and old (65 to 80 years) normal male volunteer donors. The receptor characteristics of the cells studied from the two groups of donors were not found to differ. In contrast with previous data, suggesting that there may be a genetically programmed aging of the insulin binding system, it is concluded that for both insulin and epidermal growth factor, receptor characteristics do not change with adult donor age."}
{"id": "PMID:226819", "title": "[Mediastinoscopy and thoracotomy in bronchogenic carcinoma (V) (author's transl)].", "content": "The opinion of the Bronchogenic Carcinoma Cooperative Group is that mediastinoscopy is at present an irreplaceable method for the determination of the resection limits in patients with bronchogenic carcinoma. Mediastinoscopy cannot be replaced by roentgenologic or isotopic studies of the mediastinum, since the invasion of the ganglionar capsule or of the mediastinal fat can only be determined by histopathologic examination. Following a classification based on macro- and microscopic morphological criteria, surgery has achieved a 64 percent of thoracotomies with \"presumably curative\" resections. Patients with epidermoid carcinomas were the main candidates to surgery. Lastly the role of the so-called bronchogenic carcinoma \"markers\" or substances that can indirectly indicate the course of the disease is discussed. The value of humoral and cell-mediated immunologic studies for introducing other therapeutic variants after curative surgery is pointed out. The definite conclusions regarding the clinical and surgical therapeutic aspects of the Bronchogenic Carcinoma Cooperative Group are detailed.", "contents": "[Mediastinoscopy and thoracotomy in bronchogenic carcinoma (V) (author's transl)]. The opinion of the Bronchogenic Carcinoma Cooperative Group is that mediastinoscopy is at present an irreplaceable method for the determination of the resection limits in patients with bronchogenic carcinoma. Mediastinoscopy cannot be replaced by roentgenologic or isotopic studies of the mediastinum, since the invasion of the ganglionar capsule or of the mediastinal fat can only be determined by histopathologic examination. Following a classification based on macro- and microscopic morphological criteria, surgery has achieved a 64 percent of thoracotomies with \"presumably curative\" resections. Patients with epidermoid carcinomas were the main candidates to surgery. Lastly the role of the so-called bronchogenic carcinoma \"markers\" or substances that can indirectly indicate the course of the disease is discussed. The value of humoral and cell-mediated immunologic studies for introducing other therapeutic variants after curative surgery is pointed out. The definite conclusions regarding the clinical and surgical therapeutic aspects of the Bronchogenic Carcinoma Cooperative Group are detailed."}
{"id": "PMID:226820", "title": "[Experimental induced pancreatic carcinoma after choledochojejunostomy (author's transl)].", "content": "The pancreatic carcinogen DHPN (dihydroxypropylnitrosamin) was administered to Syrian golden hamsters. By intragastric administration more pancreatic carcinomas in the head of the gland were induced than by subcutaneous injections. After choledochojejunostomy the incidence of carcinomas was only 5--7% and the lesions were similar in multiplicity and distribution without relationship to the way of administration. The importance of biliary reflux in pancreatic tumor induction is discussed and the role of bile concerning the preferred localisation of the tumors in the head of the pancreas.", "contents": "[Experimental induced pancreatic carcinoma after choledochojejunostomy (author's transl)]. The pancreatic carcinogen DHPN (dihydroxypropylnitrosamin) was administered to Syrian golden hamsters. By intragastric administration more pancreatic carcinomas in the head of the gland were induced than by subcutaneous injections. After choledochojejunostomy the incidence of carcinomas was only 5--7% and the lesions were similar in multiplicity and distribution without relationship to the way of administration. The importance of biliary reflux in pancreatic tumor induction is discussed and the role of bile concerning the preferred localisation of the tumors in the head of the pancreas."}
{"id": "PMID:226821", "title": "[Significance of the exfoliative cytodiagnosis in cases of Paget's disease of the nipple (author's transl)].", "content": "8 cases of Paget's disease of the nipple were diagnosed by means of cytological examination: in 6 patients by exfoliative, in 2 patients by aspiration biopsy cytology. The diagnoses were verified histologically. Early exfoliative cytology is recommended for early diagnosis in all cases of Paget's mamillae. This method is quick, safe, easily to be carried into effect and to apply repeatedly; but, if the process is suspected of malignancy, a trial-excision has to be carried out. A well-trained cytologist rarely needs the latter. This simple method will reduce the development of advanced Paget's disease.", "contents": "[Significance of the exfoliative cytodiagnosis in cases of Paget's disease of the nipple (author's transl)]. 8 cases of Paget's disease of the nipple were diagnosed by means of cytological examination: in 6 patients by exfoliative, in 2 patients by aspiration biopsy cytology. The diagnoses were verified histologically. Early exfoliative cytology is recommended for early diagnosis in all cases of Paget's mamillae. This method is quick, safe, easily to be carried into effect and to apply repeatedly; but, if the process is suspected of malignancy, a trial-excision has to be carried out. A well-trained cytologist rarely needs the latter. This simple method will reduce the development of advanced Paget's disease."}
{"id": "PMID:226831", "title": "Lipoproteins in experimental nephrosis: plasma levels and composition.", "content": "Experimental nephrosis was induced in rats by administration of puromycin aminonucleoside and the levels of plasma lipoproteins were examined 7 days later and compared to controls. As determined by density ultracentrifugation, VLDL, IDL, LDL, and HDL protein levels were increased by 8, 4, 5, and 5 times, respectively. These increases were accompanied by changes in lipid and apoprotein composition. The VLDL, IDL, and LDL fractions contained less triglyceride and more phospholipid and cholesterol, while HDL lipid composition was not altered. The apoprotein composition of VLDL and IDL were not measurably altered, but LDL contained less apoE. HDL had a markedly abnormal composition characterized by an almost complete absence of apoA-IV and apoE, increased apoA-1, and decreased apoC. While increased hepatic synthesis can account for much of the observed hyperlipoproteinemia in nephrosis, the changes in lipoprotein composition suggest impaired catabolism as a contributory factor.", "contents": "Lipoproteins in experimental nephrosis: plasma levels and composition. Experimental nephrosis was induced in rats by administration of puromycin aminonucleoside and the levels of plasma lipoproteins were examined 7 days later and compared to controls. As determined by density ultracentrifugation, VLDL, IDL, LDL, and HDL protein levels were increased by 8, 4, 5, and 5 times, respectively. These increases were accompanied by changes in lipid and apoprotein composition. The VLDL, IDL, and LDL fractions contained less triglyceride and more phospholipid and cholesterol, while HDL lipid composition was not altered. The apoprotein composition of VLDL and IDL were not measurably altered, but LDL contained less apoE. HDL had a markedly abnormal composition characterized by an almost complete absence of apoA-IV and apoE, increased apoA-1, and decreased apoC. While increased hepatic synthesis can account for much of the observed hyperlipoproteinemia in nephrosis, the changes in lipoprotein composition suggest impaired catabolism as a contributory factor."}
{"id": "PMID:226832", "title": "Adipose tissue lipoprotein lipase activity in type III hyperlipoproteinemia.", "content": "An impairment in the catabolism of chylomicron and very low density lipoprotein remnants appears to cause the lipid abnormalities in type III hyperlipoproteinemia. A reduction in the activity of lipoprotein lipase (LPL) has been suggested as the catabolic defect. Results in this study indicate that the activity of adipose tissue LPL measured in the fasted and fed states are in the normal range in type III hyperlipoproteinemia (fasted: type III = 2.7 +/- 1.8 mU/10(6) cells, N = 8; normals = 3.4 +/- 2.5, N = 23, p, not significant; fed: type III = 3.6 +/- 2.1, N = 7; normals = 4.8 +/- 1.8, N = 12, p, not significant). This suggests that perhaps another mechanism, such as the interaction between LPL and its lipid substrate, is abnormal, or that the activity of LPL derived from another tissue source is deficient.", "contents": "Adipose tissue lipoprotein lipase activity in type III hyperlipoproteinemia. An impairment in the catabolism of chylomicron and very low density lipoprotein remnants appears to cause the lipid abnormalities in type III hyperlipoproteinemia. A reduction in the activity of lipoprotein lipase (LPL) has been suggested as the catabolic defect. Results in this study indicate that the activity of adipose tissue LPL measured in the fasted and fed states are in the normal range in type III hyperlipoproteinemia (fasted: type III = 2.7 +/- 1.8 mU/10(6) cells, N = 8; normals = 3.4 +/- 2.5, N = 23, p, not significant; fed: type III = 3.6 +/- 2.1, N = 7; normals = 4.8 +/- 1.8, N = 12, p, not significant). This suggests that perhaps another mechanism, such as the interaction between LPL and its lipid substrate, is abnormal, or that the activity of LPL derived from another tissue source is deficient."}
{"id": "PMID:226828", "title": "[Tuberculosis in tropical Africa. Tuberculosis primary infection: some clinical aspects in tropical Africa].", "content": "A review of 140 cases of tuberculous patent primary infections from the hospital of Abidjan University and from an antituberculous unit. The disease begins slowly, general condition is rapidly altered, ventilation troubles are very frequent and so are complications as meningitis and miliary dissemination. In 11,4 p. cent of the cases, measles occurred before the primo-infection. In 38 p. cent of the cases the source of contamination could be identified and in one out of two cases, the mother proved to be responsible for it.", "contents": "[Tuberculosis in tropical Africa. Tuberculosis primary infection: some clinical aspects in tropical Africa]. A review of 140 cases of tuberculous patent primary infections from the hospital of Abidjan University and from an antituberculous unit. The disease begins slowly, general condition is rapidly altered, ventilation troubles are very frequent and so are complications as meningitis and miliary dissemination. In 11,4 p. cent of the cases, measles occurred before the primo-infection. In 38 p. cent of the cases the source of contamination could be identified and in one out of two cases, the mother proved to be responsible for it."}
{"id": "PMID:226833", "title": "Cigarette smoking, alcohol intake, and oral contraceptives: relationships to lipids and lipoproteins in adolescent school-children.", "content": "The effects of cigarette smoking, alcohol intake, and oral contraceptives on plasma cholesterol, triglyceride, high density lipoprotein cholesterol (C-HDL), and low density lipoprotein cholesterol (C-LDL) were assessed in 965 12--19-year-old school-children in the Cincinnati Lipid Research Clinic's Princeton school survey. After pair matching for age, sex, race, and total plasma cholesterol, adolescent children who smoked had mean C-HDL 6.1 mg/dl lower, and mean C-LDL 4.1 mg/dl higher, than nonsmokers (p less than 0.01). These findings for C-HDL were replicated by covariance analysis, adjusting for age, race, sex, alcohol intake, and triglyceride levels. Adolescents who drank alcohol had higher C-HDL and triglyceride levels and lower C-LDL than nondrinkers, but the differences were not significant. Adolescent females taking oral contraceptives had higher triglyceride, C-HDL, and C-LDL levels than matched controls, but the differences were not significant. If a portion of smoking's contribution to coronary heart disease risk is mediated through its inverse association with C-HDL, and if smoking habits initiated in adolescence continue into adulthood, this report provides additional physiologic data relevant to programs designed to prevent, reduce, or stop cigarette smoking in the adolescent years.", "contents": "Cigarette smoking, alcohol intake, and oral contraceptives: relationships to lipids and lipoproteins in adolescent school-children. The effects of cigarette smoking, alcohol intake, and oral contraceptives on plasma cholesterol, triglyceride, high density lipoprotein cholesterol (C-HDL), and low density lipoprotein cholesterol (C-LDL) were assessed in 965 12--19-year-old school-children in the Cincinnati Lipid Research Clinic's Princeton school survey. After pair matching for age, sex, race, and total plasma cholesterol, adolescent children who smoked had mean C-HDL 6.1 mg/dl lower, and mean C-LDL 4.1 mg/dl higher, than nonsmokers (p less than 0.01). These findings for C-HDL were replicated by covariance analysis, adjusting for age, race, sex, alcohol intake, and triglyceride levels. Adolescents who drank alcohol had higher C-HDL and triglyceride levels and lower C-LDL than nondrinkers, but the differences were not significant. Adolescent females taking oral contraceptives had higher triglyceride, C-HDL, and C-LDL levels than matched controls, but the differences were not significant. If a portion of smoking's contribution to coronary heart disease risk is mediated through its inverse association with C-HDL, and if smoking habits initiated in adolescence continue into adulthood, this report provides additional physiologic data relevant to programs designed to prevent, reduce, or stop cigarette smoking in the adolescent years."}
{"id": "PMID:226835", "title": "Pieiotropic effect of two cell wall mutants on the activity of some cell wall enzymes in the yeast Saccharomyces cerevisiae.", "content": "The two mutants (abs) and (wal) affecting the cell morphology of yeast lead also to higher in vivo activities of the cell wall enzymes acid phosphatase, invertase and melibiase.", "contents": "Pieiotropic effect of two cell wall mutants on the activity of some cell wall enzymes in the yeast Saccharomyces cerevisiae. The two mutants (abs) and (wal) affecting the cell morphology of yeast lead also to higher in vivo activities of the cell wall enzymes acid phosphatase, invertase and melibiase."}
{"id": "PMID:226836", "title": "Characterization of a plasmid mutation affecting maintenance, transfer and elimination by novobiocin.", "content": "We have isolated a mutant H group plasmid temperature-sensitive for plasmid maintenance. Unlike the wild type plasmid (pSD114), the mutant (pDT4) was eliminated at 37 degrees C and also at 30 degrees C after novobiocin treatment. The mutant plasmid interfered with host cell growth at the non-permissive temperature. Conjugative transfer of the mutant was reduced at 30 degrees C compared to the wild-type plasmid. Introduction of a coumermycin-novobiocin resistance DNA gyrase (cou) mutation into Escherichia coli prevented pDT4 elimination by novobiocin but did not affect the temperature-sensitive phenotype. The evidence indicates that the mutant plasmid used bacterial DNA gyrase for replication. Models to account for the behaviour of this unusual mutant are discussed.", "contents": "Characterization of a plasmid mutation affecting maintenance, transfer and elimination by novobiocin. We have isolated a mutant H group plasmid temperature-sensitive for plasmid maintenance. Unlike the wild type plasmid (pSD114), the mutant (pDT4) was eliminated at 37 degrees C and also at 30 degrees C after novobiocin treatment. The mutant plasmid interfered with host cell growth at the non-permissive temperature. Conjugative transfer of the mutant was reduced at 30 degrees C compared to the wild-type plasmid. Introduction of a coumermycin-novobiocin resistance DNA gyrase (cou) mutation into Escherichia coli prevented pDT4 elimination by novobiocin but did not affect the temperature-sensitive phenotype. The evidence indicates that the mutant plasmid used bacterial DNA gyrase for replication. Models to account for the behaviour of this unusual mutant are discussed."}
{"id": "PMID:226837", "title": "Dual regulation of the synthesis of the arginine pathway carbamoylphosphate synthase of Saccharomyces cerevisiae by specific and general controls of amino acid biosynthesis.", "content": "The synthesis of the arginine pathway carbamoylphosphate synthase (CPSase A) of Saccharomyces cerevisiae is subject to two control mechanisms. One mechanism is specific for CPSase A and is exerted by arginine; it probably involves a repressor-operator type of interaction. This \"specific\" mechanism regulates the expression of gene cpaI coding for the small \"glutaminase\" subunit of CPSase A but has little influence on the production of the large subunit of the enzyme, a product of gene cpaII. This large component, which alone has no biological significance, accumulates freely under conditions of arginine repression. The second mechanism is general: it controls enzyme synthesis in a number of amino acid biosynthetic pathways in addition to the arginine sequence. Two types of evidence that this \"general\" mechanism participates in the control of CPSase A synthesis are presented: (1) Derepression upon starvation for any amino acid of which the synthesis is subject to this general control; and (2) repression during growth in amino acid-rich medium. In contrast to the specific mechanism, the \"general\" mechanism regulates the expression of both the cpaI and cpaII genes.", "contents": "Dual regulation of the synthesis of the arginine pathway carbamoylphosphate synthase of Saccharomyces cerevisiae by specific and general controls of amino acid biosynthesis. The synthesis of the arginine pathway carbamoylphosphate synthase (CPSase A) of Saccharomyces cerevisiae is subject to two control mechanisms. One mechanism is specific for CPSase A and is exerted by arginine; it probably involves a repressor-operator type of interaction. This \"specific\" mechanism regulates the expression of gene cpaI coding for the small \"glutaminase\" subunit of CPSase A but has little influence on the production of the large subunit of the enzyme, a product of gene cpaII. This large component, which alone has no biological significance, accumulates freely under conditions of arginine repression. The second mechanism is general: it controls enzyme synthesis in a number of amino acid biosynthetic pathways in addition to the arginine sequence. Two types of evidence that this \"general\" mechanism participates in the control of CPSase A synthesis are presented: (1) Derepression upon starvation for any amino acid of which the synthesis is subject to this general control; and (2) repression during growth in amino acid-rich medium. In contrast to the specific mechanism, the \"general\" mechanism regulates the expression of both the cpaI and cpaII genes."}
{"id": "PMID:226838", "title": "Disturbance of tryptophan metabolism and its correction during oestrogen treatment in postmenopausal women.", "content": "A relative pyridoxine deficiency was found in all of 12 women using conjugated oestrogens unopposed by progestagsns. This was due to disturbed tryptophan metabolism, expressed in increased xanthurenic acid (XA) excretion (greater than or equal to 60 mumol/8 h) during 8 h following oral administration of 2 g L-tryptophan. The intake of synthetic oestrogens such as ethinyl oestradiol has already been found to lead to a disturbance of tryptophan metabolism and to a deficiency of vitamin B6. Now we have evidence that this is the case not only in women taking oestrogens in oral contraceptives but also as replacement therapy during the postmenopause. This disturbance is clear after 1 yr of oestrogen treatment. Xanthurenic acid excretion was only slightly increased in 3 women who used progestagens in high dosages at the same time. The biochemical changes induced could easily be corrected by administration of vitamin B6. Our cyclic treatment regimen now consists of 25 days of oestrogens per month. In the remaining days a 250 mg tablet per day of vitamin B6 is prescribed.", "contents": "Disturbance of tryptophan metabolism and its correction during oestrogen treatment in postmenopausal women. A relative pyridoxine deficiency was found in all of 12 women using conjugated oestrogens unopposed by progestagsns. This was due to disturbed tryptophan metabolism, expressed in increased xanthurenic acid (XA) excretion (greater than or equal to 60 mumol/8 h) during 8 h following oral administration of 2 g L-tryptophan. The intake of synthetic oestrogens such as ethinyl oestradiol has already been found to lead to a disturbance of tryptophan metabolism and to a deficiency of vitamin B6. Now we have evidence that this is the case not only in women taking oestrogens in oral contraceptives but also as replacement therapy during the postmenopause. This disturbance is clear after 1 yr of oestrogen treatment. Xanthurenic acid excretion was only slightly increased in 3 women who used progestagens in high dosages at the same time. The biochemical changes induced could easily be corrected by administration of vitamin B6. Our cyclic treatment regimen now consists of 25 days of oestrogens per month. In the remaining days a 250 mg tablet per day of vitamin B6 is prescribed."}
{"id": "PMID:226839", "title": "The effect of long-term oestrogen treatment on the development of osteoarthrosis at the small hand joints.", "content": "The effect of long-term oestrogen treatment of at least 5 yr on the development of osteoarthrosis was studied in 48 postmenopausal women. Osteoarthrosis at the hand joints was graded according to Kellgren's criteria, using hand X-rays. Data obtained in a normal population of 155 women served as controls as well as data obtained in 24 postmenopausal women who didnot receive oestrogen replacement therapy. No significant difference in osteoarthrosis between the treated and non-treated groups was found. The development of osteoarthrosis at the hand joints seems to be independent of the hormonal status in postmenopausal women.", "contents": "The effect of long-term oestrogen treatment on the development of osteoarthrosis at the small hand joints. The effect of long-term oestrogen treatment of at least 5 yr on the development of osteoarthrosis was studied in 48 postmenopausal women. Osteoarthrosis at the hand joints was graded according to Kellgren's criteria, using hand X-rays. Data obtained in a normal population of 155 women served as controls as well as data obtained in 24 postmenopausal women who didnot receive oestrogen replacement therapy. No significant difference in osteoarthrosis between the treated and non-treated groups was found. The development of osteoarthrosis at the hand joints seems to be independent of the hormonal status in postmenopausal women."}
{"id": "PMID:226840", "title": "Effect of postmenopausal estrogen therapy on diastolic blood pressure and bodyweight.", "content": "The effect of two forms of exogenous estrogen and a placebo on diastolic blood pressure and bodyweight was evaluated in 50 oophorectomized women. There was no significant change in bodyweight on any form of treatment, nor was there any significant elevation in mean diastolic blood pressure. However, 2 out of 49 females on conjugated estrogen showed a marked elevation of the diastolic blood pressure. It is therefore recommended that all women on exogenous estrogen treatment have their blood pressure checked at least once every 6 months. Provided this precaution is observed, changes in bodyweight or diastolic blood pressure need not be considered as potential disadvantages in the evaluation of indications for long-term estrogen treatment.", "contents": "Effect of postmenopausal estrogen therapy on diastolic blood pressure and bodyweight. The effect of two forms of exogenous estrogen and a placebo on diastolic blood pressure and bodyweight was evaluated in 50 oophorectomized women. There was no significant change in bodyweight on any form of treatment, nor was there any significant elevation in mean diastolic blood pressure. However, 2 out of 49 females on conjugated estrogen showed a marked elevation of the diastolic blood pressure. It is therefore recommended that all women on exogenous estrogen treatment have their blood pressure checked at least once every 6 months. Provided this precaution is observed, changes in bodyweight or diastolic blood pressure need not be considered as potential disadvantages in the evaluation of indications for long-term estrogen treatment."}
{"id": "PMID:226841", "title": "Psychosomatic aspects of the effect of conjugated estrogens in patients with postoperative ovarian deficiency syndrome.", "content": "Fifty-three uterine cancer patients who complained of the syndrome dur to vasomotor manifestations or psychosomatic response after ovariectomy were given Premarin tablets, 1.25 mg per day or placebo for 3 weeks and improvement in their complaints was compared from the psychosomatic aspects by the double-blind method. Premarin was significantly more effective than placebo (P less than 0.001) in the psychologically normal patients. On the other hand, no difference in the effectiveness of these drugs were found in the psychologically abnormal patients (P = 0.119). According to the self evaluation by the patients, Premarin was significantly more effective than placebo (P less than 0.05) in the psychologically normal patients. However, there was no difference in the effects of these agents in the psychologically abnormal patients.", "contents": "Psychosomatic aspects of the effect of conjugated estrogens in patients with postoperative ovarian deficiency syndrome. Fifty-three uterine cancer patients who complained of the syndrome dur to vasomotor manifestations or psychosomatic response after ovariectomy were given Premarin tablets, 1.25 mg per day or placebo for 3 weeks and improvement in their complaints was compared from the psychosomatic aspects by the double-blind method. Premarin was significantly more effective than placebo (P less than 0.001) in the psychologically normal patients. On the other hand, no difference in the effectiveness of these drugs were found in the psychologically abnormal patients (P = 0.119). According to the self evaluation by the patients, Premarin was significantly more effective than placebo (P less than 0.05) in the psychologically normal patients. However, there was no difference in the effects of these agents in the psychologically abnormal patients."}
{"id": "PMID:226842", "title": "[Electron microscopic preparation of DNA on uncharged carbon films (author's transl)].", "content": "DNA is adsorbed with densities sufficient for electron microscopy on thin uncharged carbon films. Superhelical SV 40 DNA remains superhelical on the supporting film on the contrary to the relaxation of DNA on films treated with alky dimethylbenzyl ammonium chloride (BAC). The number of superhelical turns increases to the two- or threefold of the value in solution. Investigations with a structural resolution below 1nm are possible with this preparation method.", "contents": "[Electron microscopic preparation of DNA on uncharged carbon films (author's transl)]. DNA is adsorbed with densities sufficient for electron microscopy on thin uncharged carbon films. Superhelical SV 40 DNA remains superhelical on the supporting film on the contrary to the relaxation of DNA on films treated with alky dimethylbenzyl ammonium chloride (BAC). The number of superhelical turns increases to the two- or threefold of the value in solution. Investigations with a structural resolution below 1nm are possible with this preparation method."}
{"id": "PMID:226846", "title": "Hypothesis:presynaptic receptors controlling renin release.", "content": "Presynaptic receptors have recently been identified on nerves supplying vascular smooth muscle. Renin is stored in juxtaglomerular cells in the wall of the afferent glomerular arteriole and the JG cell is probably derived from vascular smooth muscle. Nervous stimuli exert an important influence on release of renin, but the nature of the receptors involved is not agreed. We propose that there are presynaptic receptors associated with the JG apparatus as with vascular muscle and that a mechanism of this sort gives a better account of data on renin release.", "contents": "Hypothesis:presynaptic receptors controlling renin release. Presynaptic receptors have recently been identified on nerves supplying vascular smooth muscle. Renin is stored in juxtaglomerular cells in the wall of the afferent glomerular arteriole and the JG cell is probably derived from vascular smooth muscle. Nervous stimuli exert an important influence on release of renin, but the nature of the receptors involved is not agreed. We propose that there are presynaptic receptors associated with the JG apparatus as with vascular muscle and that a mechanism of this sort gives a better account of data on renin release."}
{"id": "PMID:226847", "title": "Sources of energy for the brain and physical dependence on ethanol.", "content": "This paper describes a proposed biochemical mechanism to account for physical dependence on ethanol. Long-term exposure to a continuous and plentiful supply of ethanol-derived hydrogens in NADH and ethanol-derived acetyl-CoA (AcCoA) may lead to a decreased rate of production of endogenous hydrogens in NADH and endogenous AcCoA in compensation. It is proposed that physical dependence on ethanol occurs when ketolytic- and glycolytic-based NADH and AcCoA synthetic rates fall below the rate of utilization by the brain; the brain then \"depends\" on alcohol-derived NADH and AcCoA for normal function.", "contents": "Sources of energy for the brain and physical dependence on ethanol. This paper describes a proposed biochemical mechanism to account for physical dependence on ethanol. Long-term exposure to a continuous and plentiful supply of ethanol-derived hydrogens in NADH and ethanol-derived acetyl-CoA (AcCoA) may lead to a decreased rate of production of endogenous hydrogens in NADH and endogenous AcCoA in compensation. It is proposed that physical dependence on ethanol occurs when ketolytic- and glycolytic-based NADH and AcCoA synthetic rates fall below the rate of utilization by the brain; the brain then \"depends\" on alcohol-derived NADH and AcCoA for normal function."}
{"id": "PMID:226848", "title": "Increased resistance to influenza as a possible source of heterozygote advantage in cystic fibrosis.", "content": "Cystic fibrosis is the most common lethal or semi-lethal genetic disease in Caucasians of Central European origin, among whom it is inherited as an autosomal recessive trait at a frequency approximately 10 times that expected from recurrent mutation alone. A decreased sialic acid content has been observed in cell surface glycoproteins on cystic fibrosis fibroblasts and in numerous soluble glycoprotein preparations from cystic fibrosis homozygotes. Sialic acid residues on cell surface glycoconjugates play an essential role in the binding and infectivity of myxoviruses and paramyxoviruses, including those causing pandemic influenza. It is suggested that increased resistance to these viruses conferred by similar but quantitatively smaller alterations in sialoglycoconjugate structure in cystic fibrosis heterozygotes may have provided a selective advantage to maintain the high frequency of the cystic fibrosis gene in Caucasian populations.", "contents": "Increased resistance to influenza as a possible source of heterozygote advantage in cystic fibrosis. Cystic fibrosis is the most common lethal or semi-lethal genetic disease in Caucasians of Central European origin, among whom it is inherited as an autosomal recessive trait at a frequency approximately 10 times that expected from recurrent mutation alone. A decreased sialic acid content has been observed in cell surface glycoproteins on cystic fibrosis fibroblasts and in numerous soluble glycoprotein preparations from cystic fibrosis homozygotes. Sialic acid residues on cell surface glycoconjugates play an essential role in the binding and infectivity of myxoviruses and paramyxoviruses, including those causing pandemic influenza. It is suggested that increased resistance to these viruses conferred by similar but quantitatively smaller alterations in sialoglycoconjugate structure in cystic fibrosis heterozygotes may have provided a selective advantage to maintain the high frequency of the cystic fibrosis gene in Caucasian populations."}
{"id": "PMID:226849", "title": "Enterotoxins of Escherichia coli and epilepsy.", "content": "Evidence exists that cyclic nucleotides play an important role in the stabilisation of developing synapses during the early postnatal period, and later on participate in the generation of the slow excitatory and inhibitory postsynaptic potentials. It is postulated that enterotoxins of Escherichia coli, due to their long-lasting and specific action on cyclic nucleotide-dependent processes, provide a unique mechanism for selective impairment of synaptogenesis in the abscence of cell loss. Therefore it seems possible that early enteritis, when caused by certain pathogenic strains of Escherichia coli, might be an aetiological factor in the genesis of idiopathic epilepsy.", "contents": "Enterotoxins of Escherichia coli and epilepsy. Evidence exists that cyclic nucleotides play an important role in the stabilisation of developing synapses during the early postnatal period, and later on participate in the generation of the slow excitatory and inhibitory postsynaptic potentials. It is postulated that enterotoxins of Escherichia coli, due to their long-lasting and specific action on cyclic nucleotide-dependent processes, provide a unique mechanism for selective impairment of synaptogenesis in the abscence of cell loss. Therefore it seems possible that early enteritis, when caused by certain pathogenic strains of Escherichia coli, might be an aetiological factor in the genesis of idiopathic epilepsy."}
{"id": "PMID:226850", "title": "Evidence for an aetiological role for adenovirus type 7 in the mesenteric adenitis syndrome.", "content": "Previous research has established the relationship between viral infection with adenovirus, influenza B virus and Coxsackie B virus, and mesenteric adenitis. A prospective controlled survey of the incidence of viral infection in mesenteric adenitis was undertaken in children attending a children's hospital over a period of 13 months. Eighteen patients, together with 18 controls who were matched for age, sex, and date of presentation, were studied. There were five cases of adenovirus type 7 infection in the mesenteric adenitis group and none in the control group (P=0.023--Fisher's exact test). The clinical problem at presentation is in differentiating mesenteric adenitis from appendicitis. If further work shows that viral infection is indeed more common in mesenteric adenitis, and is limited to a narrow range of viruses, then rapid identification of these viruses in children with \"acute abdomens\" would be a valuable aid to differential diagnosis.", "contents": "Evidence for an aetiological role for adenovirus type 7 in the mesenteric adenitis syndrome. Previous research has established the relationship between viral infection with adenovirus, influenza B virus and Coxsackie B virus, and mesenteric adenitis. A prospective controlled survey of the incidence of viral infection in mesenteric adenitis was undertaken in children attending a children's hospital over a period of 13 months. Eighteen patients, together with 18 controls who were matched for age, sex, and date of presentation, were studied. There were five cases of adenovirus type 7 infection in the mesenteric adenitis group and none in the control group (P=0.023--Fisher's exact test). The clinical problem at presentation is in differentiating mesenteric adenitis from appendicitis. If further work shows that viral infection is indeed more common in mesenteric adenitis, and is limited to a narrow range of viruses, then rapid identification of these viruses in children with \"acute abdomens\" would be a valuable aid to differential diagnosis."}
{"id": "PMID:226852", "title": "[Computerized tomographic localization of insulinomas (author's transl)].", "content": "Computerized  tomographic localization of insulinomas utilises the differences in radiodensity between the tumor and the adjacent pancreatic tissue. With the aid of this new technique four insulinomas have been localized preoperatively. All of the tumors had the same radiodensity. Firm, well encapsulated beta-islet-cell tumors were detected with the same ease as an insulinoma, which was soft and almost without encapsulation. The smallest tumor detected was 1.0 cm in diameter. Of the four insulinomas, localized by computer tomography of the body, only one was also detected angiographically and only two were detected sonographically.", "contents": "[Computerized tomographic localization of insulinomas (author's transl)]. Computerized  tomographic localization of insulinomas utilises the differences in radiodensity between the tumor and the adjacent pancreatic tissue. With the aid of this new technique four insulinomas have been localized preoperatively. All of the tumors had the same radiodensity. Firm, well encapsulated beta-islet-cell tumors were detected with the same ease as an insulinoma, which was soft and almost without encapsulation. The smallest tumor detected was 1.0 cm in diameter. Of the four insulinomas, localized by computer tomography of the body, only one was also detected angiographically and only two were detected sonographically."}
{"id": "PMID:226854", "title": "Lymphotropic papovaviruses isolated from African green monkey and human cells.", "content": "A lymphotropic papovavirus was isolated from a lymphoblastoid cell line of African green monkey (AGM) cells which also contained a herpesvirus and a paramyxovirus-like agent. The papovavirus was analyzed by restriction endonuclease cleavage; its biochemical and serological crossreactivity with SV40 and host range have been determined. Thus far, only B-lymphoblasts of primate and human origin have been found to be susceptible to infection. Although more than 50% of the tested monkey sera were reactive with antigens of this virus, all human sera tested failed to react. Cleavage patterns and hybridization studies with the viral DNA indicate that the virus represents a novel member of the papovavirus group that is characterized by its lymphotropic host range. Papovavirus particles were also demonstrated in a human lymphoblastoid cell line (CCRF-SB) originally derived from a leukemic child. These cells revealed nuclear fluorescence when tested with human sera, but failed to react with AGM sera. Although characterization of this agent has not yet been completed, available evidence suggests that it represents another lymphotropic papovavirus which seems to be spread within the human population.", "contents": "Lymphotropic papovaviruses isolated from African green monkey and human cells. A lymphotropic papovavirus was isolated from a lymphoblastoid cell line of African green monkey (AGM) cells which also contained a herpesvirus and a paramyxovirus-like agent. The papovavirus was analyzed by restriction endonuclease cleavage; its biochemical and serological crossreactivity with SV40 and host range have been determined. Thus far, only B-lymphoblasts of primate and human origin have been found to be susceptible to infection. Although more than 50% of the tested monkey sera were reactive with antigens of this virus, all human sera tested failed to react. Cleavage patterns and hybridization studies with the viral DNA indicate that the virus represents a novel member of the papovavirus group that is characterized by its lymphotropic host range. Papovavirus particles were also demonstrated in a human lymphoblastoid cell line (CCRF-SB) originally derived from a leukemic child. These cells revealed nuclear fluorescence when tested with human sera, but failed to react with AGM sera. Although characterization of this agent has not yet been completed, available evidence suggests that it represents another lymphotropic papovavirus which seems to be spread within the human population."}
{"id": "PMID:226855", "title": "Further studies of antibody levels to Herpes simplex virus, cytomegalovirus, measles virus, and adenovirus type 5 in Burkitt's lymphoma patients.", "content": "Sera collected from Burkitt's lymphoma (BL) patients before and after tumor manifestation were tested for antibodies to herpes simplex virus (HSV), cytomegalovirus (CMV), measles virus (MV) and adenovirus type 5, using the immunofluorescent (IF) techniques in all instances except for MV where complement fixation (CF) was used. It was found that none of these viruses showed higher antibody levels in BL patients than in controls, either before or after the appearance of the tumor. The patients came from the West Nile District of Uganda.", "contents": "Further studies of antibody levels to Herpes simplex virus, cytomegalovirus, measles virus, and adenovirus type 5 in Burkitt's lymphoma patients. Sera collected from Burkitt's lymphoma (BL) patients before and after tumor manifestation were tested for antibodies to herpes simplex virus (HSV), cytomegalovirus (CMV), measles virus (MV) and adenovirus type 5, using the immunofluorescent (IF) techniques in all instances except for MV where complement fixation (CF) was used. It was found that none of these viruses showed higher antibody levels in BL patients than in controls, either before or after the appearance of the tumor. The patients came from the West Nile District of Uganda."}
{"id": "PMID:226865", "title": "The location of SV40 specific sequences in the heterogeneous nuclear RNA of transformed mouse cells.", "content": "Rapidly labelled nuclear RNA from an SV40 transformed mouse 3T3 line was isolated, and different molecular size classes pooled. The fractions were treated with Ehrlich ascites exonuclease III for various lengths of time, and the digestion of the 3' ends of the RNA measured by the appearance of TCA-soluble material. The resulting partially degraded RNA populations were then hybridised to SV40 DNA. The data suggest that a high proportion of the viral specific sequences are located near the 3' ends of heterogeneous nuclear RNA.", "contents": "The location of SV40 specific sequences in the heterogeneous nuclear RNA of transformed mouse cells. Rapidly labelled nuclear RNA from an SV40 transformed mouse 3T3 line was isolated, and different molecular size classes pooled. The fractions were treated with Ehrlich ascites exonuclease III for various lengths of time, and the digestion of the 3' ends of the RNA measured by the appearance of TCA-soluble material. The resulting partially degraded RNA populations were then hybridised to SV40 DNA. The data suggest that a high proportion of the viral specific sequences are located near the 3' ends of heterogeneous nuclear RNA."}
{"id": "PMID:226866", "title": "Purification and properies of cAMP dependent and independent histone kinases from human leukocytes.", "content": "Histone kinase activity was purified from human polymorphonuclear leukocytes by ammonium sulphate precipitation of a 180 000 x g supernatant, followed by DEAE-cellulose chromatography and gelfiltration. On DEAE-cellulose cAMP dependent kinase activity eluted in two peaks, I and III, at 1.2 mmho and 6.5 mmho, respectively. Catalytic subunit (C) from both peaks had Mr 33 000, 3.0S. Regulatory subunit (R) from peak I and III both had Mr 33 000 upon gelfiltration, but sedimented at 2.8--3.0S and 3.0--3.2S, respectively. R2 and R4 subunits were identified. The R-C dimer from peak I and III sedimented at 4.8S and (4.8)--5.1S, respectively. The holoenzyme from peak I had Mr 165 000, 6.7S, which suggest a R2C2 structure, while that of peak III sedimented at 6.7S, but eluted at Mr 330 000 (2R2C2) by gelfiltration. The Kmapp for peak I and III enzymes were, respectively: histone IIA 0.5 mg/ml (both forms), ATP 18 microM and 23 microM, and cAMP 5 X 10(-8) M and 6.3 x 10(-8) M. Both enzymes had pH optimum 6.7--6.9 and were equally sensitive to Ca2+, temperature and protein kinase inhibitor. The substrate specificity was histone VS greater than histone IIA = histone VIS greater than casein greater than phosvitin. Peak I enzyme, but not peak III enzyme, was dissociated by histone and high ionic strength and reassociation of R and C subunits were facilitated by ATP-Mg. It is concluded that peak I and III enzymes represent type I and II cAMP dependent protein kinases, respectively. Type I comprises 20--30% of cAMP dependent protein kinase activity and is absent from the 180 000 x g supernatant of gently disrupted cells. Purified catalytic subunit had Kmapp (ATP) 20 microM with rabbit muscle glycogen synthease I as substrates. Synthase I from rabbit muscle and human leukocytes were phosphorylated by catalytic subunit to synthase D (ratio of independence less than 0.07). cAMP independent histone kinase activity eluted in one peak (Peak II) at3 mmho. The enzymatic activity sedimented at 3.4S and eluted from gelfiltration with Mr 78 000. Kmapp for ATP was 78 microM and for histone IIA 0.5 mg/ml. The enzyme was sensitive to temperature, but less sensitive than cAMP dependent protein kinase to Ca2+, and insensitive to protein kinase inhibitor. The substrate specificity was histone IIA greater than histone VS = histone VIS, while casein and phosvitin were poor substrates. Glycogen synthase I was not phosphorylated. The cAMP independent histone kinase activity comprised 15% of the total histone kinase activity in a crude homogenate of leukocytes. Its physiological substrate is unknown.", "contents": "Purification and properies of cAMP dependent and independent histone kinases from human leukocytes. Histone kinase activity was purified from human polymorphonuclear leukocytes by ammonium sulphate precipitation of a 180 000 x g supernatant, followed by DEAE-cellulose chromatography and gelfiltration. On DEAE-cellulose cAMP dependent kinase activity eluted in two peaks, I and III, at 1.2 mmho and 6.5 mmho, respectively. Catalytic subunit (C) from both peaks had Mr 33 000, 3.0S. Regulatory subunit (R) from peak I and III both had Mr 33 000 upon gelfiltration, but sedimented at 2.8--3.0S and 3.0--3.2S, respectively. R2 and R4 subunits were identified. The R-C dimer from peak I and III sedimented at 4.8S and (4.8)--5.1S, respectively. The holoenzyme from peak I had Mr 165 000, 6.7S, which suggest a R2C2 structure, while that of peak III sedimented at 6.7S, but eluted at Mr 330 000 (2R2C2) by gelfiltration. The Kmapp for peak I and III enzymes were, respectively: histone IIA 0.5 mg/ml (both forms), ATP 18 microM and 23 microM, and cAMP 5 X 10(-8) M and 6.3 x 10(-8) M. Both enzymes had pH optimum 6.7--6.9 and were equally sensitive to Ca2+, temperature and protein kinase inhibitor. The substrate specificity was histone VS greater than histone IIA = histone VIS greater than casein greater than phosvitin. Peak I enzyme, but not peak III enzyme, was dissociated by histone and high ionic strength and reassociation of R and C subunits were facilitated by ATP-Mg. It is concluded that peak I and III enzymes represent type I and II cAMP dependent protein kinases, respectively. Type I comprises 20--30% of cAMP dependent protein kinase activity and is absent from the 180 000 x g supernatant of gently disrupted cells. Purified catalytic subunit had Kmapp (ATP) 20 microM with rabbit muscle glycogen synthease I as substrates. Synthase I from rabbit muscle and human leukocytes were phosphorylated by catalytic subunit to synthase D (ratio of independence less than 0.07). cAMP independent histone kinase activity eluted in one peak (Peak II) at3 mmho. The enzymatic activity sedimented at 3.4S and eluted from gelfiltration with Mr 78 000. Kmapp for ATP was 78 microM and for histone IIA 0.5 mg/ml. The enzyme was sensitive to temperature, but less sensitive than cAMP dependent protein kinase to Ca2+, and insensitive to protein kinase inhibitor. The substrate specificity was histone IIA greater than histone VS = histone VIS, while casein and phosvitin were poor substrates. Glycogen synthase I was not phosphorylated. The cAMP independent histone kinase activity comprised 15% of the total histone kinase activity in a crude homogenate of leukocytes. Its physiological substrate is unknown."}
{"id": "PMID:226867", "title": "Determination of phosphodiesterase activity in the presence of phosphomonoesterase using bis-p-nitrophenyl phosphate.", "content": "In the presence of phosphomonoesterase contaminations the use of bis-p-nitrophenyl phosphate to measure phosphodiesterase activity gives inconclusive values because one of the products of the phosphodiesterase or nuclease reaction becomes a substrate of the contaminating enzyme. A direct determination of the hydrolyzed phosphodiesterase substrate in the UV range is possible at the isosbestic points of the transformation of the phosphomonoesterase substrate.", "contents": "Determination of phosphodiesterase activity in the presence of phosphomonoesterase using bis-p-nitrophenyl phosphate. In the presence of phosphomonoesterase contaminations the use of bis-p-nitrophenyl phosphate to measure phosphodiesterase activity gives inconclusive values because one of the products of the phosphodiesterase or nuclease reaction becomes a substrate of the contaminating enzyme. A direct determination of the hydrolyzed phosphodiesterase substrate in the UV range is possible at the isosbestic points of the transformation of the phosphomonoesterase substrate."}
{"id": "PMID:226869", "title": "The glucocorticoid domain of response: measurement of pleiotropic cellular responses by two-dimensional gel electrophoresis.", "content": "In this article, we have provided two examples of pleiotropic regulation by specific effector molecules as assayed by two-dimensional gel electrophoresis. In one case, catabolite repression in the bacterium Escherichia coli was examined by measuring the response to cyclic cAMP. In the other, the effect of dexamethasone on the rate of synthesis of over a thousand cell proteins was analyzed in HTC cells. It was found that in E. coli, cAMP regulates the synthesis of about 10 percent of the cell's proteins; both inductions and repressions are observed, but inductions clearly predominate. In HTC cells, dexamethasone induces the synthesis of seven proteins, or about 0.7 percent of the total cellular proteins; repression was not consistently observed. In another rat hepatoma line (FAZA) a similar number but essentially different set of proteins was induced. These data are discussed in terms of the notion of domains of response originally proposed by TOMKINS [1].", "contents": "The glucocorticoid domain of response: measurement of pleiotropic cellular responses by two-dimensional gel electrophoresis. In this article, we have provided two examples of pleiotropic regulation by specific effector molecules as assayed by two-dimensional gel electrophoresis. In one case, catabolite repression in the bacterium Escherichia coli was examined by measuring the response to cyclic cAMP. In the other, the effect of dexamethasone on the rate of synthesis of over a thousand cell proteins was analyzed in HTC cells. It was found that in E. coli, cAMP regulates the synthesis of about 10 percent of the cell's proteins; both inductions and repressions are observed, but inductions clearly predominate. In HTC cells, dexamethasone induces the synthesis of seven proteins, or about 0.7 percent of the total cellular proteins; repression was not consistently observed. In another rat hepatoma line (FAZA) a similar number but essentially different set of proteins was induced. These data are discussed in terms of the notion of domains of response originally proposed by TOMKINS [1]."}
{"id": "PMID:226870", "title": "Regulation of mouse mammary tumor virus gene expression by glucocorticoid hormones.", "content": "Several laboratories have documented that glucocorticoid hormones markedly stimulate the expression of mouse mammary tumor virus genes in a variety of mouse mammary tumor cells and in infected heterologous cells. The effect of the hormone appears to be a rapid and specific augmentation of the synthesis of viral RNA, mediated by interaction with glucocorticoid receptor proteins. The availability of virus-specific reagents and recent developments in the molecular biology of RNA tumor viruses now permit a highly refined analysis of hormonal regulation in this experimental system.", "contents": "Regulation of mouse mammary tumor virus gene expression by glucocorticoid hormones. Several laboratories have documented that glucocorticoid hormones markedly stimulate the expression of mouse mammary tumor virus genes in a variety of mouse mammary tumor cells and in infected heterologous cells. The effect of the hormone appears to be a rapid and specific augmentation of the synthesis of viral RNA, mediated by interaction with glucocorticoid receptor proteins. The availability of virus-specific reagents and recent developments in the molecular biology of RNA tumor viruses now permit a highly refined analysis of hormonal regulation in this experimental system."}
{"id": "PMID:226872", "title": "Influences of adrenocortical hormones on pituitary and brain function.", "content": "Adrenocortical secretions influence neuroendocrine function and behavior, and it is possible to recognize separate physiologic actions of gluco- and mineralocorticoids. The search for neuroanatomical sites and cellular modes of adrenocorticoid action has revealed a system of putative glucocorticoid receptors in neurons of the hippocampus, septum, amygdala, and entorhinal cortex, and in the pituitary. No part of the brain is totally devoid of receptor activity, however, and glial cells may also contain glucocorticoid receptors. Mineralocorticoid receptors are less well characterized neuroanatomically or biochemically. One reason for this is the considerable degree to which both gluco- and mineralocorticoids bind to both classes of receptors in vitro. Another reason may be the overwhelming quantitative predominance of glucocorticoid over mineralocorticoid receptors in neural tissue. Glucocorticoid receptors of the pituitary, which have a high avidity for dexamethasone, appear to participate in the delayed negative feedback effects of glucocoticoids. Functional correlates of neural glucocorticoid receptors remain to be clearly established. Among the possibilities are several reported effects on hippocampal neural activity that have an onset latency of 20--30 min and a duration of several hours. The relative rapidity of such effects does not preclude genomic mediation, as genomic effects of glucocorticoids on thymus lymphocytes have been detected within as little as 15 min of steroid application [117]. What are not so far explained by the intracellular receptor mechanism are the extremely rapid effects of glucocorticoids such as the rate-sensitive negative feedback on CRF and ACTH secretion. These may involve a direct action of the steroid on cell membranes in the pituitary and hypothalamus.", "contents": "Influences of adrenocortical hormones on pituitary and brain function. Adrenocortical secretions influence neuroendocrine function and behavior, and it is possible to recognize separate physiologic actions of gluco- and mineralocorticoids. The search for neuroanatomical sites and cellular modes of adrenocorticoid action has revealed a system of putative glucocorticoid receptors in neurons of the hippocampus, septum, amygdala, and entorhinal cortex, and in the pituitary. No part of the brain is totally devoid of receptor activity, however, and glial cells may also contain glucocorticoid receptors. Mineralocorticoid receptors are less well characterized neuroanatomically or biochemically. One reason for this is the considerable degree to which both gluco- and mineralocorticoids bind to both classes of receptors in vitro. Another reason may be the overwhelming quantitative predominance of glucocorticoid over mineralocorticoid receptors in neural tissue. Glucocorticoid receptors of the pituitary, which have a high avidity for dexamethasone, appear to participate in the delayed negative feedback effects of glucocoticoids. Functional correlates of neural glucocorticoid receptors remain to be clearly established. Among the possibilities are several reported effects on hippocampal neural activity that have an onset latency of 20--30 min and a duration of several hours. The relative rapidity of such effects does not preclude genomic mediation, as genomic effects of glucocorticoids on thymus lymphocytes have been detected within as little as 15 min of steroid application [117]. What are not so far explained by the intracellular receptor mechanism are the extremely rapid effects of glucocorticoids such as the rate-sensitive negative feedback on CRF and ACTH secretion. These may involve a direct action of the steroid on cell membranes in the pituitary and hypothalamus."}
{"id": "PMID:226873", "title": "Inhibition of glucose transport in fat cells and activation of lipolysis by glucocorticoids.", "content": "The major effects of glucocorticoids on white fat are shown in Fig. 1. The glucocorticoid diffuses into the cytosol of fat cells where it binds to a soluble receptor. The steroid-receptor complex then enters the nucleus where RNA synthesis is increased. The next step may be a selective increase in synthesis of protein(s). In any event, there is an inhibition of the membrane-bound glucose transport system and an increase in the ability of lipolytic agents to activate triglyceride lipolysis. There is also a decrease in phosphoenolpyruvate carboxykinase, lipoprotein lipase, and fatty acid synthetase that occurs after a somewhat longer lag period than is required for inhibition of glucose transport or lipolysis activation. Whether these effects are independent or secondary to the glucose transport inhibition and lipolysis activation remains to be established.", "contents": "Inhibition of glucose transport in fat cells and activation of lipolysis by glucocorticoids. The major effects of glucocorticoids on white fat are shown in Fig. 1. The glucocorticoid diffuses into the cytosol of fat cells where it binds to a soluble receptor. The steroid-receptor complex then enters the nucleus where RNA synthesis is increased. The next step may be a selective increase in synthesis of protein(s). In any event, there is an inhibition of the membrane-bound glucose transport system and an increase in the ability of lipolytic agents to activate triglyceride lipolysis. There is also a decrease in phosphoenolpyruvate carboxykinase, lipoprotein lipase, and fatty acid synthetase that occurs after a somewhat longer lag period than is required for inhibition of glucose transport or lipolysis activation. Whether these effects are independent or secondary to the glucose transport inhibition and lipolysis activation remains to be established."}
{"id": "PMID:226875", "title": "[Vitamin D-metabolism and rickets (author's transl)].", "content": "By new methods Vitamin D metabolites can now be determined in small quantities of biological fluids. These methods have revealed further details about Vitamin D metabolism as well as the pathogeneses and therapy of the various types of rickets. A review of this topic will be presented.", "contents": "[Vitamin D-metabolism and rickets (author's transl)]. By new methods Vitamin D metabolites can now be determined in small quantities of biological fluids. These methods have revealed further details about Vitamin D metabolism as well as the pathogeneses and therapy of the various types of rickets. A review of this topic will be presented."}
{"id": "PMID:226878", "title": "[Urethrotomy of urethral strictures in adults (author's transl)].", "content": "The late results of optical \"cold\" urethrotomy so far have shown that this method of treatment of urethral stenoses and strictures of any type and location is superior to all other operative possibilities, the more so as the operation, carried out under local anesthesia, scarcely distresses the patient and he can easily recover. The danger of secondary injury is certainly reduced by the optical control yet bleeding may occasionally occur later. It should also be borne in mind in making the indication that with a relatively narrow urethra a high degree of iatrigenic scar stricture may develop. Relapses (ca. 12 to 47%) occur relatively seldom compared with other procedures. The relapse rate is affected by chronic urinary tract infections, the nature and duration of subsequent indwelling catheter treatment and the length and severity of the stricture.", "contents": "[Urethrotomy of urethral strictures in adults (author's transl)]. The late results of optical \"cold\" urethrotomy so far have shown that this method of treatment of urethral stenoses and strictures of any type and location is superior to all other operative possibilities, the more so as the operation, carried out under local anesthesia, scarcely distresses the patient and he can easily recover. The danger of secondary injury is certainly reduced by the optical control yet bleeding may occasionally occur later. It should also be borne in mind in making the indication that with a relatively narrow urethra a high degree of iatrigenic scar stricture may develop. Relapses (ca. 12 to 47%) occur relatively seldom compared with other procedures. The relapse rate is affected by chronic urinary tract infections, the nature and duration of subsequent indwelling catheter treatment and the length and severity of the stricture."}
{"id": "PMID:226880", "title": "Survival of apurinic SV40 DNA in the d-complementation group of xeroderma pigmentosum.", "content": "The survival of depurinated Form I SV40 DNA was studied in normal human fibroblasts and in D-complementation Xeroderma pigmentosum (XP) fibroblasts. Survival was measured with an infective center assay. Heat-acid and methyl methanesulfonate (MMS) were used as depurinating agents. After 3 hrs of depurination by heat--acid treatment, infectivity in normal cells was less than 15% of the controls compared to more than 50% for the XP D cell strains. Similar results were obtained with MMS-treated DNA. These results are contrary to expectation since apurinic endonuclease activity, which is presumed to be involved in the repair of apurinic sites, is much lower in XP D cell strains than in normal cell strains. Our results indicate that another mechanism for the repair of apurinic sites could exist.", "contents": "Survival of apurinic SV40 DNA in the d-complementation group of xeroderma pigmentosum. The survival of depurinated Form I SV40 DNA was studied in normal human fibroblasts and in D-complementation Xeroderma pigmentosum (XP) fibroblasts. Survival was measured with an infective center assay. Heat-acid and methyl methanesulfonate (MMS) were used as depurinating agents. After 3 hrs of depurination by heat--acid treatment, infectivity in normal cells was less than 15% of the controls compared to more than 50% for the XP D cell strains. Similar results were obtained with MMS-treated DNA. These results are contrary to expectation since apurinic endonuclease activity, which is presumed to be involved in the repair of apurinic sites, is much lower in XP D cell strains than in normal cell strains. Our results indicate that another mechanism for the repair of apurinic sites could exist."}
{"id": "PMID:226883", "title": "Increase in lipoprotein lipase during clofibrate treatment of hypertriglyceridemia in patients on hemodialysis.", "content": "In 11 hypertriglyceridemic patients on hemodialysis, clofibrate (1 to 1.50 g per week) reduced plasma triglyceride (-40 +/- 20%, P less than 0.001), very-low-density-lipoprotein triglyceride (-44 +/- 20%, P less than 0.001) and very-low-density lipoprotein cholesterol (-39 +/- 25%, P less than 0.01), and it increased high-density-lipoprotein cholesterol (82 +/- 106%, P less than 0.005). Low pretreatment lipoprotein-lipase activity in adipose-tissue specimens and postheparin plasma increased to normal with clofibrate, whereas low hepatic triglyceride lipase activity did not change. The reduced very-low-density-lipoprotein triglyceride correlated with the increased lipoprotein-lipase activity in adipose tissue (rs = 0.792, P less than 0.02, n = 8) and postheparin plasma (rs = 0.851, P less than 0.02, n = 8), whereas increased high-density-lipoprotein cholesterol correlated with changes in this activity in adipose tissue (rs = 0.696, P less than 0.06) and post-heparin plasma (rs = 0.679, P less than 0.10). There was no correlation between changes in hepatic triglyceride lipase activity and plasma lipids during treatment. Reduced lipoprotein-lipase activity may cause hypertriglyceridemia and decreased high-density-lipoprotein cholesterol in patients on hemodialysis; clofibrate may correct these abnormalities by increasing lipoprotein-lipase activity to normal.", "contents": "Increase in lipoprotein lipase during clofibrate treatment of hypertriglyceridemia in patients on hemodialysis. In 11 hypertriglyceridemic patients on hemodialysis, clofibrate (1 to 1.50 g per week) reduced plasma triglyceride (-40 +/- 20%, P less than 0.001), very-low-density-lipoprotein triglyceride (-44 +/- 20%, P less than 0.001) and very-low-density lipoprotein cholesterol (-39 +/- 25%, P less than 0.01), and it increased high-density-lipoprotein cholesterol (82 +/- 106%, P less than 0.005). Low pretreatment lipoprotein-lipase activity in adipose-tissue specimens and postheparin plasma increased to normal with clofibrate, whereas low hepatic triglyceride lipase activity did not change. The reduced very-low-density-lipoprotein triglyceride correlated with the increased lipoprotein-lipase activity in adipose tissue (rs = 0.792, P less than 0.02, n = 8) and postheparin plasma (rs = 0.851, P less than 0.02, n = 8), whereas increased high-density-lipoprotein cholesterol correlated with changes in this activity in adipose tissue (rs = 0.696, P less than 0.06) and post-heparin plasma (rs = 0.679, P less than 0.10). There was no correlation between changes in hepatic triglyceride lipase activity and plasma lipids during treatment. Reduced lipoprotein-lipase activity may cause hypertriglyceridemia and decreased high-density-lipoprotein cholesterol in patients on hemodialysis; clofibrate may correct these abnormalities by increasing lipoprotein-lipase activity to normal."}
{"id": "PMID:226881", "title": "Increased endoneurial fluid pressure in galactose neuropathy.", "content": "Edema and increased endoneurial fluid pressure developed in peripheral nerves of rats that received a diet containing 40% galactose during a study of the role of sugar alcohols in producing neuropathy. Fluid pressure was elevated starting in the third month and progressed to a fivefold increase over control values by the fifth month. Microscopic examination confirmed the presence of edema as predicted by the sorbitol theory, which is often invoked to explain the pathogenesis of diabetic neuropathy.", "contents": "Increased endoneurial fluid pressure in galactose neuropathy. Edema and increased endoneurial fluid pressure developed in peripheral nerves of rats that received a diet containing 40% galactose during a study of the role of sugar alcohols in producing neuropathy. Fluid pressure was elevated starting in the third month and progressed to a fivefold increase over control values by the fifth month. Microscopic examination confirmed the presence of edema as predicted by the sorbitol theory, which is often invoked to explain the pathogenesis of diabetic neuropathy."}
{"id": "PMID:226884", "title": "Activation of suppressor T cells during Epstein-Barr-virus-induced infectious mononucleosis.", "content": "Infectious mononucleosis is caused by the Epstein-Barr virus (EBV), an unusual human pathogen because it preferentially infects B lymphocytes and consequently activates them to produce immunoglobulins. When cultures of lymphocytes from patients with infectious mononucleosis were stimulated with polyclonal activators, unseparated cells failed to produce immunoglobulins, whereas purified B cells responded normally. Cocultures demonstrated profound suppressor T-cell activity in blood from patients with infectious mononucleosis. Early in this disease, circulating immunoglobulin-secreting cells were elevated, but during the second week their number was strikingly depressed. These data indicate that during infectious mononucleosis, EBV causes polyclonal activation of B cells, reflected by hypergammaglobulinemia and increased circulating immunoglobulin-secreting cells. Next, suppressor T cells become activated and inhibit further B-cell activation. Thus, activation of suppressor T cells in infectious mononucleosis provides a unique additional mechanism of host defense because these T cells inhibit the activation and proliferation of an important target of the causative virus.", "contents": "Activation of suppressor T cells during Epstein-Barr-virus-induced infectious mononucleosis. Infectious mononucleosis is caused by the Epstein-Barr virus (EBV), an unusual human pathogen because it preferentially infects B lymphocytes and consequently activates them to produce immunoglobulins. When cultures of lymphocytes from patients with infectious mononucleosis were stimulated with polyclonal activators, unseparated cells failed to produce immunoglobulins, whereas purified B cells responded normally. Cocultures demonstrated profound suppressor T-cell activity in blood from patients with infectious mononucleosis. Early in this disease, circulating immunoglobulin-secreting cells were elevated, but during the second week their number was strikingly depressed. These data indicate that during infectious mononucleosis, EBV causes polyclonal activation of B cells, reflected by hypergammaglobulinemia and increased circulating immunoglobulin-secreting cells. Next, suppressor T cells become activated and inhibit further B-cell activation. Thus, activation of suppressor T cells in infectious mononucleosis provides a unique additional mechanism of host defense because these T cells inhibit the activation and proliferation of an important target of the causative virus."}
{"id": "PMID:226882", "title": "Treatment of denervated muscle by gangliosides.", "content": "Short-duration cooling of the nerve to the extensor digitorum longus muscle of the rat in vivo induced partially reversible denervation of the muscle and atrophy in the type 2 muscle fibers. Increases in cyclic adenosine monophosphate, cyclic guanosine monophosphate phosphodiesterase, adenylate cyclase, and guanylate cyclase were observed in the denervated muscle. Treatment with gangliosides of the bovine brain cortex seemed to improve the excitability of the surviving motor units and to encourage recovery of neuromuscular trophic control, but it did not affect the nerve conduction velocity or the contractile properties of the denervated muscle.", "contents": "Treatment of denervated muscle by gangliosides. Short-duration cooling of the nerve to the extensor digitorum longus muscle of the rat in vivo induced partially reversible denervation of the muscle and atrophy in the type 2 muscle fibers. Increases in cyclic adenosine monophosphate, cyclic guanosine monophosphate phosphodiesterase, adenylate cyclase, and guanylate cyclase were observed in the denervated muscle. Treatment with gangliosides of the bovine brain cortex seemed to improve the excitability of the surviving motor units and to encourage recovery of neuromuscular trophic control, but it did not affect the nerve conduction velocity or the contractile properties of the denervated muscle."}
{"id": "PMID:226886", "title": "Studies on a strain of Fusarium solani (Mart.) Sacc. Isolated from a case of mycotic keratitis.", "content": "A strain of Fusarium solani (Mart.) Sacc. (IMI-216517), isolated from a patient of mycotic keratitis, produced experimental keratomycosis in albino rabbit cornea and survived in internal tissues of albino mice for varying periods. Alantolactone, isolated from the plant - Inula racemosa Hook. f. exhibited marked in vitro fungistatic activity against this strain of F. solani at 100-200 microgram/ml concentrations. The strain was less sensitive to amphotericin B and showed more acid than alkaline proteinase and phosphatase activities.", "contents": "Studies on a strain of Fusarium solani (Mart.) Sacc. Isolated from a case of mycotic keratitis. A strain of Fusarium solani (Mart.) Sacc. (IMI-216517), isolated from a patient of mycotic keratitis, produced experimental keratomycosis in albino rabbit cornea and survived in internal tissues of albino mice for varying periods. Alantolactone, isolated from the plant - Inula racemosa Hook. f. exhibited marked in vitro fungistatic activity against this strain of F. solani at 100-200 microgram/ml concentrations. The strain was less sensitive to amphotericin B and showed more acid than alkaline proteinase and phosphatase activities."}
{"id": "PMID:226887", "title": "[Effect of tin on rats. 1. Inverse voltammetric determination of tin in the presence of lead in biological material after extraction].", "content": "By means of inverse polarography, the authors determined tin selectively after double extraction with diethylammonium diethyl dithiocarbamate (DADDTC) in perchloric solution. The recovery rates were: in potatoes, 91.7 +/- 5.8%; in beef kidney, 85.0 +/- 22.7%; in beef liver 79.9 +/- 13.8%; and in milk, 69.8 +/- 11.4%. Possible interferences from other elements with the tin determination are discussed.", "contents": "[Effect of tin on rats. 1. Inverse voltammetric determination of tin in the presence of lead in biological material after extraction]. By means of inverse polarography, the authors determined tin selectively after double extraction with diethylammonium diethyl dithiocarbamate (DADDTC) in perchloric solution. The recovery rates were: in potatoes, 91.7 +/- 5.8%; in beef kidney, 85.0 +/- 22.7%; in beef liver 79.9 +/- 13.8%; and in milk, 69.8 +/- 11.4%. Possible interferences from other elements with the tin determination are discussed."}
{"id": "PMID:226888", "title": "Three new types of viral oncogene of cellular origin specific for haematopoietic cell transformation.", "content": "The RNAs of seven replication-defective leukaemia virus (DLV) strains contain three types of unique sequences, which correlate with the capacity of a given virus strain to transform erythroblasts, macrophage-like cells and myeloblasts, respectively. These sequences, termed erb, mac and myb, have their counterparts in the normal DNA of avian and mammalian species. Our results indicate that DLVs represent recombinants between a common 'vector' related to a chicken endogenous virus and one of three types of cellular gene possibly involved in haematopoietic differentiation.", "contents": "Three new types of viral oncogene of cellular origin specific for haematopoietic cell transformation. The RNAs of seven replication-defective leukaemia virus (DLV) strains contain three types of unique sequences, which correlate with the capacity of a given virus strain to transform erythroblasts, macrophage-like cells and myeloblasts, respectively. These sequences, termed erb, mac and myb, have their counterparts in the normal DNA of avian and mammalian species. Our results indicate that DLVs represent recombinants between a common 'vector' related to a chicken endogenous virus and one of three types of cellular gene possibly involved in haematopoietic differentiation."}
{"id": "PMID:226889", "title": "T4 DNA topoisomerase: a new ATP-dependent enzyme essential for initiation of T4 bacteriophage DNA replication.", "content": "A novel ATP-dependent DNA topoisomerase which makes reversible double-strand breaks in the DNA double helix has been purified to near homogeneity from T4 bacteriophage-infected Escherichia coli cells. Genetic data suggest that this activity is essential for initiating T4 DNA replication forks in vivo.", "contents": "T4 DNA topoisomerase: a new ATP-dependent enzyme essential for initiation of T4 bacteriophage DNA replication. A novel ATP-dependent DNA topoisomerase which makes reversible double-strand breaks in the DNA double helix has been purified to near homogeneity from T4 bacteriophage-infected Escherichia coli cells. Genetic data suggest that this activity is essential for initiating T4 DNA replication forks in vivo."}
{"id": "PMID:226892", "title": "Combined effects of adrenaline and insulin on active electrogenic Na+-K+ transport in rat soleus muscle.", "content": "Both beta 2-adrenoreceptor stimulants (such as adrenaline and salbutamol) and insulin can increase active Na+-K+ transport and hyperpolarise skeletal cells. Thus, adrenaline and insulin, which are otherwise antagonistic regulators of several metabolic processes, have one action in common, namely, stimulation of active ion translocation. This is especially interesting as cyclic AMP stimulates Na+-K+ transport, whereas a lowering of the cytoplasmic concentration of cyclic AMP has been proposed as an early signal in the action of insulin. Here we report the results of experiments in which the active Na+-K+ transport and membrane potential (EM) of rat soleus muscles were studied during the action of supramaximal doses of insulin and beta 2-adrenoreceptor stimulants, alone and in combination. We conclude that the stimulant action of insulin on active electrogenic Na+-K+ transport is unlikely to be evoked by a lowering of the intracellular concentration of cyclic AMP.", "contents": "Combined effects of adrenaline and insulin on active electrogenic Na+-K+ transport in rat soleus muscle. Both beta 2-adrenoreceptor stimulants (such as adrenaline and salbutamol) and insulin can increase active Na+-K+ transport and hyperpolarise skeletal cells. Thus, adrenaline and insulin, which are otherwise antagonistic regulators of several metabolic processes, have one action in common, namely, stimulation of active ion translocation. This is especially interesting as cyclic AMP stimulates Na+-K+ transport, whereas a lowering of the cytoplasmic concentration of cyclic AMP has been proposed as an early signal in the action of insulin. Here we report the results of experiments in which the active Na+-K+ transport and membrane potential (EM) of rat soleus muscles were studied during the action of supramaximal doses of insulin and beta 2-adrenoreceptor stimulants, alone and in combination. We conclude that the stimulant action of insulin on active electrogenic Na+-K+ transport is unlikely to be evoked by a lowering of the intracellular concentration of cyclic AMP."}
{"id": "PMID:226894", "title": "A different genetic code in human mitochondria.", "content": "Comparison of the human mitochrondial DNA sequence of the cytochrome oxidase subunit II gene and the sequence of the corresponding beef heart protein shows that UGA is used as a tryptophan codon and not as a termination codon and suggests that AUA may be a methionine and not an isoleucine codon. The cytochrome oxidase II gene is contiguous at its 5' end with a tRNAAsp gene and there are only 25 bases at its 3' end before a tRNALys gene. These tRNA'S are different from all other known tRNA sequences.", "contents": "A different genetic code in human mitochondria. Comparison of the human mitochrondial DNA sequence of the cytochrome oxidase subunit II gene and the sequence of the corresponding beef heart protein shows that UGA is used as a tryptophan codon and not as a termination codon and suggests that AUA may be a methionine and not an isoleucine codon. The cytochrome oxidase II gene is contiguous at its 5' end with a tRNAAsp gene and there are only 25 bases at its 3' end before a tRNALys gene. These tRNA'S are different from all other known tRNA sequences."}
{"id": "PMID:226895", "title": "Pharmacological characteristics of beta-adrenoceptor binding sites in intact and sympathectomized rat spleen.", "content": "[3H]-(--)-Dihydroalprenolol ([3H]-DHA) binds to rat spleen membranes with a dissociation equilibrium constant (KD) of about 0.7 nM and a maximal number of binding sites of 272 fmoles x mg protein-1. Approximately 90% of the sites labelled by 1 nM [3H]-DHA possess classical properties of beta-adrenoceptors. The labelled ligand is stereospecifically displaced by the isomers of propranolol and the order of potency of agonists is: isoprenaline greater than adrenaline greater than noradrenaline. Highly selective beta 1 antagonists such as practolol and atenolol displaced [3H]-DHA from spleen membranes in a biphasic manner indicating the co-existence of beta 1 and beta 2 sites (30--35% beta 1; 65--70% beta 2) in this tissue. Support for this classification was provided by the binding of the beta 2 agonist procaterol to spleen membranes. This drug possessed high affinity only for those sites that have low affinity for the beta 1 selective agents. Chemical sympathectomy induced by chronic 6-hydroxydopamine administration did not alter the number or the pharmacological properties of beta-adrenoceptor binding sites. The results suggest that both beta 1 and beta 2 adrenoceptors are probably postsynaptic in spleen.", "contents": "Pharmacological characteristics of beta-adrenoceptor binding sites in intact and sympathectomized rat spleen. [3H]-(--)-Dihydroalprenolol ([3H]-DHA) binds to rat spleen membranes with a dissociation equilibrium constant (KD) of about 0.7 nM and a maximal number of binding sites of 272 fmoles x mg protein-1. Approximately 90% of the sites labelled by 1 nM [3H]-DHA possess classical properties of beta-adrenoceptors. The labelled ligand is stereospecifically displaced by the isomers of propranolol and the order of potency of agonists is: isoprenaline greater than adrenaline greater than noradrenaline. Highly selective beta 1 antagonists such as practolol and atenolol displaced [3H]-DHA from spleen membranes in a biphasic manner indicating the co-existence of beta 1 and beta 2 sites (30--35% beta 1; 65--70% beta 2) in this tissue. Support for this classification was provided by the binding of the beta 2 agonist procaterol to spleen membranes. This drug possessed high affinity only for those sites that have low affinity for the beta 1 selective agents. Chemical sympathectomy induced by chronic 6-hydroxydopamine administration did not alter the number or the pharmacological properties of beta-adrenoceptor binding sites. The results suggest that both beta 1 and beta 2 adrenoceptors are probably postsynaptic in spleen."}
{"id": "PMID:226898", "title": "Metabolism of red blood cells in chronic renal failure. I. Glycolytic enzyme levels.", "content": "This paper starts a series on red blood cell (RBC) metabolism in patients with chronic renal failure (CRF). The glycolytic enzyme levels and in vitro half-lives of these patients' RBCs were determined. A number of enzymes (hexokinase, glucose-6-phosphate isomerase, fructose-6-phosphate kinase, aldolase, glyceraldehyde-3-phosphate dehydrogenase and lactate dehydrogenase) showed higher activities than in normal control RBCs. Other enzyme activities were normal. These results were discussed and several possible mechanisms considered. We favour the point of view of a shortened life span of the RBCs in CRF, making the most unstable enzymes of the glycolytic sequence appear increase as compared with normal controls.", "contents": "Metabolism of red blood cells in chronic renal failure. I. Glycolytic enzyme levels. This paper starts a series on red blood cell (RBC) metabolism in patients with chronic renal failure (CRF). The glycolytic enzyme levels and in vitro half-lives of these patients' RBCs were determined. A number of enzymes (hexokinase, glucose-6-phosphate isomerase, fructose-6-phosphate kinase, aldolase, glyceraldehyde-3-phosphate dehydrogenase and lactate dehydrogenase) showed higher activities than in normal control RBCs. Other enzyme activities were normal. These results were discussed and several possible mechanisms considered. We favour the point of view of a shortened life span of the RBCs in CRF, making the most unstable enzymes of the glycolytic sequence appear increase as compared with normal controls."}
{"id": "PMID:226899", "title": "Collagenase activity of rat kidney with glomerulonephritis is inhibited by erythromycin.", "content": "Collagenolytic activity of rat kidney with glomerulonephritis (GN) of Masugi's type was determined by a series of biological experiments. The determination was carried out during the heterologous phase of the disease together with inhibition studies in vivo and in vitro. Erythromycin has been tested in vivo for its inhibitory activity and an activity of collagenase was found in untreated rats with GN only, the panel treated with erythromycin did not show any collagenolysis. Statistical calculations indicate the significance of the inhibition (p less than 0.001). In addition, kidneys of test animals with GN have been investigated for their enzymatic activity and the inhibition by erythromycin in vitro where the kidneys failed to show collagenolytic activity. It can be concluded that erythromycin is able to inhibit in vivo and in vitro the activity of the collagenolytic enzyme produced by polymorphonuclear leukocytes during the heterologous phase of the nephritis, an effect which leads to the recovery of the physiological equilibrium of the protease and its inhibitor.", "contents": "Collagenase activity of rat kidney with glomerulonephritis is inhibited by erythromycin. Collagenolytic activity of rat kidney with glomerulonephritis (GN) of Masugi's type was determined by a series of biological experiments. The determination was carried out during the heterologous phase of the disease together with inhibition studies in vivo and in vitro. Erythromycin has been tested in vivo for its inhibitory activity and an activity of collagenase was found in untreated rats with GN only, the panel treated with erythromycin did not show any collagenolysis. Statistical calculations indicate the significance of the inhibition (p less than 0.001). In addition, kidneys of test animals with GN have been investigated for their enzymatic activity and the inhibition by erythromycin in vitro where the kidneys failed to show collagenolytic activity. It can be concluded that erythromycin is able to inhibit in vivo and in vitro the activity of the collagenolytic enzyme produced by polymorphonuclear leukocytes during the heterologous phase of the nephritis, an effect which leads to the recovery of the physiological equilibrium of the protease and its inhibitor."}
{"id": "PMID:226900", "title": "Influence of theophylline on concentrations of cyclic 3',5'-adenosine monophosphate and cyclic 3',5'-guanosine monophosphate of rat brain.", "content": "The influence of theophylline (2.5--100 mg/kg p.o.) on cyclic 3',5'-adenosine monophosphate (cAMP) and cyclic 3',5'-guanosine monophosphate (cGMP) in brain of Sprague-Dawley rats (0.5--3.0 hr after administration of theophylline) was investigated. It was found that theophylline increases cAMP and cGMP levels when administered in a dose of 25 mg/kg or higher. A significant decrease of cGMP level was observed after administration of 10 mg/kg. The results of this study suggest that the influence of theophylline on cyclic nucleotide levels of rat brain is the result of two factors: (a) inhibitory properties of theophylline on cAMP and cGMP phosphodiesterases and (b) competition of theophylline with adenosine.", "contents": "Influence of theophylline on concentrations of cyclic 3',5'-adenosine monophosphate and cyclic 3',5'-guanosine monophosphate of rat brain. The influence of theophylline (2.5--100 mg/kg p.o.) on cyclic 3',5'-adenosine monophosphate (cAMP) and cyclic 3',5'-guanosine monophosphate (cGMP) in brain of Sprague-Dawley rats (0.5--3.0 hr after administration of theophylline) was investigated. It was found that theophylline increases cAMP and cGMP levels when administered in a dose of 25 mg/kg or higher. A significant decrease of cGMP level was observed after administration of 10 mg/kg. The results of this study suggest that the influence of theophylline on cyclic nucleotide levels of rat brain is the result of two factors: (a) inhibitory properties of theophylline on cAMP and cGMP phosphodiesterases and (b) competition of theophylline with adenosine."}
{"id": "PMID:226902", "title": "Effect of intraventricular histamine on hormone secretion in dogs.", "content": "In pentobarbital-anesthetized dogs, infusion of a low dose of histamine directly into the third ventricle increased plasma ACTH concentration. The increase was unaffected by metiamide, a drug which blocks H2 receptors, but was abolished by mepyramine, a drug which blocks H1 receptors. Mepyramine alone did not produce a decrease in plasma ACTH concentration in stressed dogs. Infusion of the H1 agonist 2-methylhistamine increased plasma ACTH concentration, whereas infusion of the H2 agonist 4-methylhistamine decreased plasma ACTH concentration and blocked the response to surgical stress. Histamine, 2-methylhistamine and 4-methylhistamine had no statistically significant effect on plasma renin activity, blood pressure, or heart rate, and histamine had no effect on plasma prolactin concentration. There were no consistent, specific effects on growth hormone secretion. We conclude that activation of central H1 receptors increases ACTH secretion in dogs, and that activation of central H2 receptors decreases ACTH secretion. Some of the reported effects of cyproheptadine and other drugs on ACTH secretion may be due to their antihistamine activity.", "contents": "Effect of intraventricular histamine on hormone secretion in dogs. In pentobarbital-anesthetized dogs, infusion of a low dose of histamine directly into the third ventricle increased plasma ACTH concentration. The increase was unaffected by metiamide, a drug which blocks H2 receptors, but was abolished by mepyramine, a drug which blocks H1 receptors. Mepyramine alone did not produce a decrease in plasma ACTH concentration in stressed dogs. Infusion of the H1 agonist 2-methylhistamine increased plasma ACTH concentration, whereas infusion of the H2 agonist 4-methylhistamine decreased plasma ACTH concentration and blocked the response to surgical stress. Histamine, 2-methylhistamine and 4-methylhistamine had no statistically significant effect on plasma renin activity, blood pressure, or heart rate, and histamine had no effect on plasma prolactin concentration. There were no consistent, specific effects on growth hormone secretion. We conclude that activation of central H1 receptors increases ACTH secretion in dogs, and that activation of central H2 receptors decreases ACTH secretion. Some of the reported effects of cyproheptadine and other drugs on ACTH secretion may be due to their antihistamine activity."}
{"id": "PMID:226903", "title": "Effects of neonatal hydrocortisone treatment of pituitary and adrenocortical response to stress in young rats.", "content": "Administration of corticosteroids to rat pups within the first several days of life results in retardation of several behavioral, neurophysiological, and biochemical developmental patterns. At 25 days of age, animals treated neonatally with 1.0, 0.5, or 0.1 mg hydrocortisone acetate showed dose-dependent decreases in plasma ACTH following 2.5 min continuous exposure to ether. On day 20, plasma corticosterone values did not differ between these groups 15 min after ether stress, but lower values were seen 60 min after ether in animals treated at birth with 0.5 mg hydrocortisone. At 45--48 days of age, hydrocortisone-treated animals exposed to one of 2 different stressors showed decreased plasma corticosterone response to stress; females had lower corticosterone levels following both stressors, while males showed suppressed corticosterone levels following exposure to the mild (novelty) but not to the intense (ether) stress. These data demonstrate that neonatal exposure to hydrocortisone results in decreased CNS-pituitary responsivity to stress at 20--25 days of age, and that the adrenocortical response to stress in impaired at 45--48 days of age.", "contents": "Effects of neonatal hydrocortisone treatment of pituitary and adrenocortical response to stress in young rats. Administration of corticosteroids to rat pups within the first several days of life results in retardation of several behavioral, neurophysiological, and biochemical developmental patterns. At 25 days of age, animals treated neonatally with 1.0, 0.5, or 0.1 mg hydrocortisone acetate showed dose-dependent decreases in plasma ACTH following 2.5 min continuous exposure to ether. On day 20, plasma corticosterone values did not differ between these groups 15 min after ether stress, but lower values were seen 60 min after ether in animals treated at birth with 0.5 mg hydrocortisone. At 45--48 days of age, hydrocortisone-treated animals exposed to one of 2 different stressors showed decreased plasma corticosterone response to stress; females had lower corticosterone levels following both stressors, while males showed suppressed corticosterone levels following exposure to the mild (novelty) but not to the intense (ether) stress. These data demonstrate that neonatal exposure to hydrocortisone results in decreased CNS-pituitary responsivity to stress at 20--25 days of age, and that the adrenocortical response to stress in impaired at 45--48 days of age."}
{"id": "PMID:226908", "title": "Overnight sleep EEG and cerebrospinal fluid monoamines in seizures induced by movement.", "content": "Clinical, electrical and biochemical studies in an eight years old boy with movement-induced seizures were reported. The attack was usually triggered by sudden initiation of movement, but rarely occurred without any apparent movement. Repeated jumping provoked attacks constantly, which was recorded cinematographically. No abnormality was found either in ictal or interictal EEGs. Haloperidol aggravated the condition, but 1-DOPA had no effect, while DPH (100 mg/day) controlled attacks perfectly with the serum DPH concentration of just 2.0 ug/dl. In overnight sleep analysis, sleep rhythms and characters of REM sleep were not differed significantly from the standard. After DPH therapy, stabilization of sleep in general was noticed; that is, total sleep time prolonged, number of sleep stages decreased and interrupting awakening disappeared. Probenecid loading test revealed that 5-HIAA was normal, HVA high, and large amount of octopamine was detected in CSF.", "contents": "Overnight sleep EEG and cerebrospinal fluid monoamines in seizures induced by movement. Clinical, electrical and biochemical studies in an eight years old boy with movement-induced seizures were reported. The attack was usually triggered by sudden initiation of movement, but rarely occurred without any apparent movement. Repeated jumping provoked attacks constantly, which was recorded cinematographically. No abnormality was found either in ictal or interictal EEGs. Haloperidol aggravated the condition, but 1-DOPA had no effect, while DPH (100 mg/day) controlled attacks perfectly with the serum DPH concentration of just 2.0 ug/dl. In overnight sleep analysis, sleep rhythms and characters of REM sleep were not differed significantly from the standard. After DPH therapy, stabilization of sleep in general was noticed; that is, total sleep time prolonged, number of sleep stages decreased and interrupting awakening disappeared. Probenecid loading test revealed that 5-HIAA was normal, HVA high, and large amount of octopamine was detected in CSF."}
{"id": "PMID:226914", "title": "High density lipoprotein cholesterol and other serum lipids in New Zealand Maoris.", "content": "The pattern of fasting serum lipids, with emphasis on high density lipoprotein cholesterol, and the relationship of the lipids with each other and with other risk factors is examined in a population based sample of New Zealand Maoris. There are no sex differences in the distribution of total cholesterol and cholesterol fractions but triglycerides are higher in men. High density lipoprotein cholesterol levels are lower in Maoris than reported in other populations. High density lipoprotein cholesterol is negatively correlated with low density lipoprotein cholesterol but not associated with total cholesterol. High density lipoprotein cholesterol is negatively correlated with body mass index and in men high density lipoprotein cholesterol levels are higher in current alcohol drinkers. The possible relationship between the low levels of high density lipoprotein cholesterol and the high risk of coronary heart disease in Maoris requires investigation.", "contents": "High density lipoprotein cholesterol and other serum lipids in New Zealand Maoris. The pattern of fasting serum lipids, with emphasis on high density lipoprotein cholesterol, and the relationship of the lipids with each other and with other risk factors is examined in a population based sample of New Zealand Maoris. There are no sex differences in the distribution of total cholesterol and cholesterol fractions but triglycerides are higher in men. High density lipoprotein cholesterol levels are lower in Maoris than reported in other populations. High density lipoprotein cholesterol is negatively correlated with low density lipoprotein cholesterol but not associated with total cholesterol. High density lipoprotein cholesterol is negatively correlated with body mass index and in men high density lipoprotein cholesterol levels are higher in current alcohol drinkers. The possible relationship between the low levels of high density lipoprotein cholesterol and the high risk of coronary heart disease in Maoris requires investigation."}
{"id": "PMID:226915", "title": "Trigeminal neuralgia: an overview.", "content": "Facial pain is a perplexing problem confronting all who practice the healing arts. The purpose of this article is to concentrate on one aspect of facial pain--trigeminal neuralgia. An overview of this entity is presented by demonstrating current concepts in its etiology, diagnosis, and treatment. Classically, trigeminal neuralgia has been described as a paroxysmal, lancinating, knifelike pain which is limited to the anatomic pathways of the fifth cranial nerve. It is a chronic facial pain that is amenable to medical and surgical treatment when correctly diagnosed. A knowledge of the anatomy of the fifth cranial nerve is essential for a correct diagnosis of trigeminal neuralgia. A description of the anatomy is not within the scope of this article, and the reader is referred to any of the standard anatomy textbooks for review.", "contents": "Trigeminal neuralgia: an overview. Facial pain is a perplexing problem confronting all who practice the healing arts. The purpose of this article is to concentrate on one aspect of facial pain--trigeminal neuralgia. An overview of this entity is presented by demonstrating current concepts in its etiology, diagnosis, and treatment. Classically, trigeminal neuralgia has been described as a paroxysmal, lancinating, knifelike pain which is limited to the anatomic pathways of the fifth cranial nerve. It is a chronic facial pain that is amenable to medical and surgical treatment when correctly diagnosed. A knowledge of the anatomy of the fifth cranial nerve is essential for a correct diagnosis of trigeminal neuralgia. A description of the anatomy is not within the scope of this article, and the reader is referred to any of the standard anatomy textbooks for review."}
{"id": "PMID:226921", "title": "The effects of abdominal loading on rib cage distortion in premature infants.", "content": "The action of the diaphragm in inspiration is to decrease intrathoracic pressure and raise abdominal pressure, which elevates the rib cage. In the supine position, the rise in abdominal pressure is smaller because of the lack of abdominal muscle tone. In premature infants the inward pull of the diaphragm on the very compliant ribs causes inward movement on inspiration (ie, distortion) which is exacerbated by the lack of intercostal muscle activity during rapid eye movement (REM) sleep, their predominant state. We raised abdominal pressure by means of an inflatable cuff in 12 newborn infants (gestation 28 to 40 weeks) to try to improve inspiratory coupling of the rib cage and diaphragm. There was no significant change in minute ventilation, indicating no ventilatory impairment. In all studies in which there was distortion, abdominal loading produced a reduction or abolition of distortion (P less than .01). Abdominal loading may be useful in reducing diaphragmatic activity in premature infants.", "contents": "The effects of abdominal loading on rib cage distortion in premature infants. The action of the diaphragm in inspiration is to decrease intrathoracic pressure and raise abdominal pressure, which elevates the rib cage. In the supine position, the rise in abdominal pressure is smaller because of the lack of abdominal muscle tone. In premature infants the inward pull of the diaphragm on the very compliant ribs causes inward movement on inspiration (ie, distortion) which is exacerbated by the lack of intercostal muscle activity during rapid eye movement (REM) sleep, their predominant state. We raised abdominal pressure by means of an inflatable cuff in 12 newborn infants (gestation 28 to 40 weeks) to try to improve inspiratory coupling of the rib cage and diaphragm. There was no significant change in minute ventilation, indicating no ventilatory impairment. In all studies in which there was distortion, abdominal loading produced a reduction or abolition of distortion (P less than .01). Abdominal loading may be useful in reducing diaphragmatic activity in premature infants."}
{"id": "PMID:226916", "title": "Granular cell tumors of the tongue.", "content": "We have presented a series of 19 new cases of granular cell tumors of the tongue. This benign condition is often difficult to diagnose if an adequate biopsy specimen has not been obtained. Insufficient biopsy material that includes only the overlying pseudoepitheliomatous hyperplasia may distort the pathologic picture. Review of frozen sections should provide an accurate diagnosis, and local surgical excision should resolve the problem completely.", "contents": "Granular cell tumors of the tongue. We have presented a series of 19 new cases of granular cell tumors of the tongue. This benign condition is often difficult to diagnose if an adequate biopsy specimen has not been obtained. Insufficient biopsy material that includes only the overlying pseudoepitheliomatous hyperplasia may distort the pathologic picture. Review of frozen sections should provide an accurate diagnosis, and local surgical excision should resolve the problem completely."}
{"id": "PMID:226917", "title": "Malignant fibrous histiocytoma of the maxillary sinus.", "content": "A malignant fibrous histiocytoma from the maxillary sinus of a 51-year-old woman was treated surgically with adjuvant chemotherapy and radiation. The maxillary sinus is an unusual site for this rare and controversial neoplasm, as a review of the literature shows.", "contents": "Malignant fibrous histiocytoma of the maxillary sinus. A malignant fibrous histiocytoma from the maxillary sinus of a 51-year-old woman was treated surgically with adjuvant chemotherapy and radiation. The maxillary sinus is an unusual site for this rare and controversial neoplasm, as a review of the literature shows."}
{"id": "PMID:226918", "title": "Diagnosis of juvenile nasopharyngeal angiofibroma by computed tomography.", "content": "Juvenile nasopharyngeal angiofibroma is a highly vascular neoplasms that tends to spread in the various fissures and foraminia of the nasopharynz. Polytomography and angiography have added greatly to the diagnosis and management of this tumor through accurate preoperative assessment. Computed tomography has given an additional sophisticated, precise method for evaluating the extent of juvenile nasopharyngeal angiofibroma. Computed tomography shows, in detail, the extension of the tumor into the pterygopalatine fossa with widening of the pterygopalatine fossa and anterior bowing of the posterior wall of the maxillary sinus. With this correct information about tumor location, surgical or radiation treatment can be appropriately planned, with a probable improvement of cure rates and reduction of recurrences.", "contents": "Diagnosis of juvenile nasopharyngeal angiofibroma by computed tomography. Juvenile nasopharyngeal angiofibroma is a highly vascular neoplasms that tends to spread in the various fissures and foraminia of the nasopharynz. Polytomography and angiography have added greatly to the diagnosis and management of this tumor through accurate preoperative assessment. Computed tomography has given an additional sophisticated, precise method for evaluating the extent of juvenile nasopharyngeal angiofibroma. Computed tomography shows, in detail, the extension of the tumor into the pterygopalatine fossa with widening of the pterygopalatine fossa and anterior bowing of the posterior wall of the maxillary sinus. With this correct information about tumor location, surgical or radiation treatment can be appropriately planned, with a probable improvement of cure rates and reduction of recurrences."}
{"id": "PMID:226922", "title": "The diagnosis of insulinoma in a child in the absence of fasting hyperinsulinemia.", "content": "This report concerns an 8-year-old girl with fasting hypoglycemia caused by a functional islet cell adenoma. During two separate fasting studies the blood glucose concentrations decreased to abnormally low levels yet the serum concentrations of insulin were consistently within the accepted range of normal. This report illustrates the diagnostic value of three simple functional tests--the inhibitory effect of insulin on ketogenesis and on glycogenolysis and the stimulatory effect of leucine on insulin secretion.", "contents": "The diagnosis of insulinoma in a child in the absence of fasting hyperinsulinemia. This report concerns an 8-year-old girl with fasting hypoglycemia caused by a functional islet cell adenoma. During two separate fasting studies the blood glucose concentrations decreased to abnormally low levels yet the serum concentrations of insulin were consistently within the accepted range of normal. This report illustrates the diagnostic value of three simple functional tests--the inhibitory effect of insulin on ketogenesis and on glycogenolysis and the stimulatory effect of leucine on insulin secretion."}
{"id": "PMID:226924", "title": "Triglyceride and cholesterol concentrations in whole serum and in serum lipoproteins in Reye syndrome.", "content": "Triglyceride and cholesterol concentrations in whole serum and in the serum lipoprotein fractions were measured during the course of hospitalization in six patients with Reye syndrome, four of whom survived. Very low density lipoprotein (VLDL) triglycerides were significantly lower on admission than on the last day of hospitalization. However, no VLDL triglyceride value was below the normal range. Triglyceride transport was increased in low density lipoprotein (LDL) and high density lipoprotein (HDL) fractions. LDL and HDL cholesterol concentrations were low on admission and decreased further during hospitalization. The changes in LDL and HDL cholesterol concentrations were more severe among nonsurvivors. No HDL cholesterol was detected in nonsurvivors on the last day of hospitalization. These results suggest that decreased VLDL triglycerides may not play an important role in the development of fatty liver and that decreased LDL and HDL cholesterol concentrations may be of prognostic value in Reye syndrome.", "contents": "Triglyceride and cholesterol concentrations in whole serum and in serum lipoproteins in Reye syndrome. Triglyceride and cholesterol concentrations in whole serum and in the serum lipoprotein fractions were measured during the course of hospitalization in six patients with Reye syndrome, four of whom survived. Very low density lipoprotein (VLDL) triglycerides were significantly lower on admission than on the last day of hospitalization. However, no VLDL triglyceride value was below the normal range. Triglyceride transport was increased in low density lipoprotein (LDL) and high density lipoprotein (HDL) fractions. LDL and HDL cholesterol concentrations were low on admission and decreased further during hospitalization. The changes in LDL and HDL cholesterol concentrations were more severe among nonsurvivors. No HDL cholesterol was detected in nonsurvivors on the last day of hospitalization. These results suggest that decreased VLDL triglycerides may not play an important role in the development of fatty liver and that decreased LDL and HDL cholesterol concentrations may be of prognostic value in Reye syndrome."}
{"id": "PMID:226930", "title": "[The treatment of Cushing's syndrome by selective excision of pituitary adenoma. 3 cases (author's transl)].", "content": "In three patients suffering from Cushing's disease, exploration revealed an enclosed pituitary adenoma in one case and a microadenoma in two cases. Selective excision via a transphenoidal approach resulted in cure of Cushing's disease as reflected by complete regression of clinical signs and the restoration of circadian rythm of cortisol. Regular follow-up over a period of more than two years showed the persistence of normal regulation of the corticotrophic sector of the pituitary.", "contents": "[The treatment of Cushing's syndrome by selective excision of pituitary adenoma. 3 cases (author's transl)]. In three patients suffering from Cushing's disease, exploration revealed an enclosed pituitary adenoma in one case and a microadenoma in two cases. Selective excision via a transphenoidal approach resulted in cure of Cushing's disease as reflected by complete regression of clinical signs and the restoration of circadian rythm of cortisol. Regular follow-up over a period of more than two years showed the persistence of normal regulation of the corticotrophic sector of the pituitary."}
{"id": "PMID:226931", "title": "[Acetylcholine receptors (author's transl)].", "content": "The actions of acetylcholine can be classified as nicotine-like or muscarine-like. Nicotinic actions of acetylcholine are seen at the skeletal neuromuscular junction and at autonomic ganglia whereas muscarinic transmission occurs at parasympathetic effector organs and in the brain. The sites on the membrane surface of a neuronal cell body or dendrite where acetylcholine acts is called a receptor site. There has been marked progress in the last few years in the identification and quantification of acetylcholine receptors by biochemical methods by means of specific radioactive ligands of very high activity and very high affinity for these receptors. Using these techniques it has been possible to: determine the regional distribution of nicotinic and muscarinic receptors in the brain, evaluate new drugs acting on these receptors, and determine the concentration of these receptors in neurologic disorders.", "contents": "[Acetylcholine receptors (author's transl)]. The actions of acetylcholine can be classified as nicotine-like or muscarine-like. Nicotinic actions of acetylcholine are seen at the skeletal neuromuscular junction and at autonomic ganglia whereas muscarinic transmission occurs at parasympathetic effector organs and in the brain. The sites on the membrane surface of a neuronal cell body or dendrite where acetylcholine acts is called a receptor site. There has been marked progress in the last few years in the identification and quantification of acetylcholine receptors by biochemical methods by means of specific radioactive ligands of very high activity and very high affinity for these receptors. Using these techniques it has been possible to: determine the regional distribution of nicotinic and muscarinic receptors in the brain, evaluate new drugs acting on these receptors, and determine the concentration of these receptors in neurologic disorders."}
{"id": "PMID:226938", "title": "Electron microscopic mapping of proteins bound to herpes simplex virus DNA.", "content": "Exonuclease digestion experiments have suggested that there is a protein(s) bound close to one or both ends of herpes simplex virus-1 (HSV) DNA. The existence of such bound proteins has been positively demonstrated and their positions on the HSV genome determined by application of a newly developed method for electron microscopic mapping of proteins bound to nucleic acids. Purified HSV DNA was treated with dinitrofluorobenzene under conditions that covalently attach the dinitrophenyl (DNP) group to the proteins in a protein-nucleic acid complex. The HSV DNA-protein-(DNP)n complex was treated with rabbit anti-DNP IgG, and, in some cases, additionally treated with monovalent Fab fragments of goat anti-rabbit IgG, and mounted for examination in the electron microscope. Electron opaque dots representing the protein-(DNP)n-(IgG)m complex were seen on the HSV DNA. Direct measurements of the positions of the protein, as well as partial denaturation mapping, indicate that there are four positions for protein bound to HSV DNA: two near but not at the two ends and two at sites corresponding to the internal inverted repeats of the ends. These results suggest that there is a specific protein binding sequence within the direct terminal repeat of HSV DNA. The previous observation that HSV DNA is more sensitive to digestion by a 3' than by a 5' exonuclease then indicates that the bound protein(s) is more intimately associated with one strand of the specific sequence than with the complementary strand.", "contents": "Electron microscopic mapping of proteins bound to herpes simplex virus DNA. Exonuclease digestion experiments have suggested that there is a protein(s) bound close to one or both ends of herpes simplex virus-1 (HSV) DNA. The existence of such bound proteins has been positively demonstrated and their positions on the HSV genome determined by application of a newly developed method for electron microscopic mapping of proteins bound to nucleic acids. Purified HSV DNA was treated with dinitrofluorobenzene under conditions that covalently attach the dinitrophenyl (DNP) group to the proteins in a protein-nucleic acid complex. The HSV DNA-protein-(DNP)n complex was treated with rabbit anti-DNP IgG, and, in some cases, additionally treated with monovalent Fab fragments of goat anti-rabbit IgG, and mounted for examination in the electron microscope. Electron opaque dots representing the protein-(DNP)n-(IgG)m complex were seen on the HSV DNA. Direct measurements of the positions of the protein, as well as partial denaturation mapping, indicate that there are four positions for protein bound to HSV DNA: two near but not at the two ends and two at sites corresponding to the internal inverted repeats of the ends. These results suggest that there is a specific protein binding sequence within the direct terminal repeat of HSV DNA. The previous observation that HSV DNA is more sensitive to digestion by a 3' than by a 5' exonuclease then indicates that the bound protein(s) is more intimately associated with one strand of the specific sequence than with the complementary strand."}
{"id": "PMID:226939", "title": "Nonhistone proteins HMG1 and HMG2 unwind DNA double helix.", "content": "In a previous communication we have shown that both HMG1 and HMG2 nonhistone proteins change the DNA helical structure and the binding of HMG1 and HMG2 to DNA induces a net unwinding equivalent of DNA double helix (Javaherian, K., Liu, L. F. and Wang, J. C. (1978) Science, 199, 1345-1346). Employing melting absorption technique, we now show that in the presence of salt HMG1 and HMG2 destabilize DNA whereas in the absence of salt, they both stabilize DNA molecules. Consequently the folded structure of HMG must play an important role in melting DNA. Furthermore, by measuring topological winding number using competition unwinding experiments, we conclude that HMG1 has a higher affinity for a single-stranded DNA relative to double-stranded DNA. These results together suggest that HMG1 and HMG2 unwind DNA double helix by local denaturation of the DNA base pairs. The net unwinding angles have been measured to be 22 degrees and 26 degrees per molecule of HMG1 and HMG2 respectively.", "contents": "Nonhistone proteins HMG1 and HMG2 unwind DNA double helix. In a previous communication we have shown that both HMG1 and HMG2 nonhistone proteins change the DNA helical structure and the binding of HMG1 and HMG2 to DNA induces a net unwinding equivalent of DNA double helix (Javaherian, K., Liu, L. F. and Wang, J. C. (1978) Science, 199, 1345-1346). Employing melting absorption technique, we now show that in the presence of salt HMG1 and HMG2 destabilize DNA whereas in the absence of salt, they both stabilize DNA molecules. Consequently the folded structure of HMG must play an important role in melting DNA. Furthermore, by measuring topological winding number using competition unwinding experiments, we conclude that HMG1 has a higher affinity for a single-stranded DNA relative to double-stranded DNA. These results together suggest that HMG1 and HMG2 unwind DNA double helix by local denaturation of the DNA base pairs. The net unwinding angles have been measured to be 22 degrees and 26 degrees per molecule of HMG1 and HMG2 respectively."}
{"id": "PMID:226940", "title": "Salt-and histone H1-induced structural changes of reconstituted minichromosomes.", "content": "Structural changes of reconstituted SV 40 minichromosomes have been studied in relation to the salt concentration and addition of histone H1 by sedimentation and electron microscopy. Sedimentation data are represented as functions of the NaCl concentration and the Debye-H\u00fcckel electrostatic screening radius 1/alpha. The latter representation which proved to provide more information revealed three structural states of the SV 40 reconstitutes which can be additionally characterized by electron microscopy as follows: Expanded or relaxed conformation including free DNA spacers between the nucleosomes at low salt concentration (approx. 0.001 M-0.05 M NaCl), increasing condensation at moderate salt concentration (approx. 0.05 M-0.3 M NaCl) and expansion of this condensed state above approx. 0.3 M NaCl. The condensation of the reconstitutes at moderate salt concentration does not require the presence of histone H1. H1 seems to stabilize the condensed state against electrostatic expansion. The condensation might be promoted by salt-dependent conformational changes of naked superhelical DNA as revealed by sedimentation measurements.", "contents": "Salt-and histone H1-induced structural changes of reconstituted minichromosomes. Structural changes of reconstituted SV 40 minichromosomes have been studied in relation to the salt concentration and addition of histone H1 by sedimentation and electron microscopy. Sedimentation data are represented as functions of the NaCl concentration and the Debye-H\u00fcckel electrostatic screening radius 1/alpha. The latter representation which proved to provide more information revealed three structural states of the SV 40 reconstitutes which can be additionally characterized by electron microscopy as follows: Expanded or relaxed conformation including free DNA spacers between the nucleosomes at low salt concentration (approx. 0.001 M-0.05 M NaCl), increasing condensation at moderate salt concentration (approx. 0.05 M-0.3 M NaCl) and expansion of this condensed state above approx. 0.3 M NaCl. The condensation of the reconstitutes at moderate salt concentration does not require the presence of histone H1. H1 seems to stabilize the condensed state against electrostatic expansion. The condensation might be promoted by salt-dependent conformational changes of naked superhelical DNA as revealed by sedimentation measurements."}
{"id": "PMID:226941", "title": "Structural investigations of DNA-histone complexes. A spin label study.", "content": "We have prepared two acridine spin labels, 6-chloro-9-[4-(2,2,6,6-tetramethyl-1-piperidinyloxy)amino]-2-methoxyacridine (I) and 9-[4-(2,2,6,6-tetramethyl-1-piperidinyloxy)amino]-acridine (II) and have used them to study the binding of lysine-rich histone (H1) to DNA using electron spin resonance (ESR). ESR spectra of I in the presence of DNA, polydA-polydT and polydG-polydC were characteristic of highly immobilized radicals with maximum hyperfine splitting (2T11) of 59G, 62.5G and 59G respectively. However, the 2T11 values for II in the same systems were 55.5G, 55.5G and 62.5G respectively. Addition of H1 at a low P/D released ionically bound I and II from DNA. In the presence of 0.1 M NaCl, which prevents ionic binding, H1 still caused a significant release of bound II but not I from DNA. At a high P/D (with or without NaCl) H1 caused no displacement of either I or II. Our findings suggest that H1 does not affect the intercalating sites and probably binds to one of the grooves of DNA, most probably the major groove, and specifically in the A-T-rich regions.", "contents": "Structural investigations of DNA-histone complexes. A spin label study. We have prepared two acridine spin labels, 6-chloro-9-[4-(2,2,6,6-tetramethyl-1-piperidinyloxy)amino]-2-methoxyacridine (I) and 9-[4-(2,2,6,6-tetramethyl-1-piperidinyloxy)amino]-acridine (II) and have used them to study the binding of lysine-rich histone (H1) to DNA using electron spin resonance (ESR). ESR spectra of I in the presence of DNA, polydA-polydT and polydG-polydC were characteristic of highly immobilized radicals with maximum hyperfine splitting (2T11) of 59G, 62.5G and 59G respectively. However, the 2T11 values for II in the same systems were 55.5G, 55.5G and 62.5G respectively. Addition of H1 at a low P/D released ionically bound I and II from DNA. In the presence of 0.1 M NaCl, which prevents ionic binding, H1 still caused a significant release of bound II but not I from DNA. At a high P/D (with or without NaCl) H1 caused no displacement of either I or II. Our findings suggest that H1 does not affect the intercalating sites and probably binds to one of the grooves of DNA, most probably the major groove, and specifically in the A-T-rich regions."}
{"id": "PMID:226942", "title": "The nucleotide sequence of the 5' terminus of vesicular stomatitis virus RNA.", "content": "We have determined the nucleotide sequence for the first 50 nucleotides at the 5' terminus of vesicular stomatitis virus (VSV) genome RNA. This sequence is identical to that of the in vitro RNA polymerase product synthesized by defective interfering (DI) particles of VSV. These results confirm previous conclusions rengarding DI and standard viral terminal sequences based on hybridization studies and earlier sequencing of the DI polymerase product RNA.", "contents": "The nucleotide sequence of the 5' terminus of vesicular stomatitis virus RNA. We have determined the nucleotide sequence for the first 50 nucleotides at the 5' terminus of vesicular stomatitis virus (VSV) genome RNA. This sequence is identical to that of the in vitro RNA polymerase product synthesized by defective interfering (DI) particles of VSV. These results confirm previous conclusions rengarding DI and standard viral terminal sequences based on hybridization studies and earlier sequencing of the DI polymerase product RNA."}
{"id": "PMID:226943", "title": "Synthesis and enzymatic properties of deoxyribooligonucleotides containing methyl and phenylphosphonate linkages.", "content": "Chemical methods for the synthesis of short deoxyribooligonucleotides containing methyl and phenylphosphonodiester linkages have been developed. The interaction of two such nonionic dinucleotide analogs, T(pCH3)T and T(pC6H5)T, with several enzymes has been investigated. Because of the phosphonate linkage each dinucleotide exists as a diastereomeric pair as shown by thin layer chromatography and enzymatic studies. Both isomers of each dinucleotide can be phosphorylated by T4-polynucleotide kinase in the presence of [gamma-32P]ATP. Only one of the diastereoisomers of each dinucleotide is slowly hydrolyzed by snake venom phosphodiesterase and acts as an inhibitor of the enzyme-catalyzed hydrolysis of 5'-labeled oligothymidylic acid. Both isomers of each dinucleotide analog are completely resistant to hydrolysis by spleen phosphodiesterase.", "contents": "Synthesis and enzymatic properties of deoxyribooligonucleotides containing methyl and phenylphosphonate linkages. Chemical methods for the synthesis of short deoxyribooligonucleotides containing methyl and phenylphosphonodiester linkages have been developed. The interaction of two such nonionic dinucleotide analogs, T(pCH3)T and T(pC6H5)T, with several enzymes has been investigated. Because of the phosphonate linkage each dinucleotide exists as a diastereomeric pair as shown by thin layer chromatography and enzymatic studies. Both isomers of each dinucleotide can be phosphorylated by T4-polynucleotide kinase in the presence of [gamma-32P]ATP. Only one of the diastereoisomers of each dinucleotide is slowly hydrolyzed by snake venom phosphodiesterase and acts as an inhibitor of the enzyme-catalyzed hydrolysis of 5'-labeled oligothymidylic acid. Both isomers of each dinucleotide analog are completely resistant to hydrolysis by spleen phosphodiesterase."}
{"id": "PMID:226944", "title": "Orientation of herpes simplex virus type 1 immediate early mRNA's.", "content": "We have determined the orientation of 4 immediate early (IE) mRNA's on the herpes simplex virus type 1 genome by mapping cDNA's complementary to the 3'-termini of messages. These IE mRNA's are transcribed by a pre-existing cell RNA polymerase, and we propose a model which allows their synthesis from a circular template using a single virus promoter region. The promoter region, which is located in the two repetitive DNA regions which flank the short unique region of the virus genome, may serve to initiate bidirectional transcription of these IE mRNA's.", "contents": "Orientation of herpes simplex virus type 1 immediate early mRNA's. We have determined the orientation of 4 immediate early (IE) mRNA's on the herpes simplex virus type 1 genome by mapping cDNA's complementary to the 3'-termini of messages. These IE mRNA's are transcribed by a pre-existing cell RNA polymerase, and we propose a model which allows their synthesis from a circular template using a single virus promoter region. The promoter region, which is located in the two repetitive DNA regions which flank the short unique region of the virus genome, may serve to initiate bidirectional transcription of these IE mRNA's."}
{"id": "PMID:226946", "title": "Effects of early infectious bursal disease virus infection on immunity to Newcastle disease in adult chickens.", "content": "Experimental infection with infectious bursal disease virus (IBDV) at hatching or at 3 weeks of age in White Leghorn chickens without maternally derived antibodies to IBDV resulted in a depression in the antibody response of chickens to Newcastle disease vaccination (NDV) at 4 weeks of age and increased the susceptibility of those birds to challenge with virulent NDV. Infection of non-IBDV immune chickens with IBDV at hatching, but not at 3 weeks of age, also depressed the antibody response of chickens vaccinated at 18, 30, or 42 weeks of age, but had no effect on the susceptibility of those birds to challenge with virulent NDV. Prior exposure to IBDV did not alter disease resistance afforded a bird by NDV vaccination at 18, 30, or 42 weeks of age. However, IBDV infection at hatching did render chickens that were not vaccinated against ND more susceptible to challenge with virulent NDV at 21, 33, or 45 weeks of age than unvaccinated birds which were not infected with IBDV or unvaccinated chickens infected with IBDV at 3 weeks of age.", "contents": "Effects of early infectious bursal disease virus infection on immunity to Newcastle disease in adult chickens. Experimental infection with infectious bursal disease virus (IBDV) at hatching or at 3 weeks of age in White Leghorn chickens without maternally derived antibodies to IBDV resulted in a depression in the antibody response of chickens to Newcastle disease vaccination (NDV) at 4 weeks of age and increased the susceptibility of those birds to challenge with virulent NDV. Infection of non-IBDV immune chickens with IBDV at hatching, but not at 3 weeks of age, also depressed the antibody response of chickens vaccinated at 18, 30, or 42 weeks of age, but had no effect on the susceptibility of those birds to challenge with virulent NDV. Prior exposure to IBDV did not alter disease resistance afforded a bird by NDV vaccination at 18, 30, or 42 weeks of age. However, IBDV infection at hatching did render chickens that were not vaccinated against ND more susceptible to challenge with virulent NDV at 21, 33, or 45 weeks of age than unvaccinated birds which were not infected with IBDV or unvaccinated chickens infected with IBDV at 3 weeks of age."}
{"id": "PMID:226947", "title": "Effect of fasting and fasting and refeeding on hepatic and renal gluconeogenic enzymes in the chicken.", "content": "The effect of fasting and fasting and refeeding on hepatic and renal gluconeogenic enzyme activities were studied in six-week-old chickens (Gallus domesticus: New Hampshire male x Columbian female). Hepatic pyruvate carboxylase appeared not to be affected by fasting, but the renal enzyme activity increased in four-day fasted chickens. The hepatic mitochondrial and cytosolic phosphoenolpyruvate carboxykinases were essentially not affected by fasting. The renal mitochondrial phosphoenolpyruvate carboxykinase showed a slight increase in activity only after a four-day fast, but the cytosolic enzyme activity increased markedly already after a two-day fast. Also the activities of the hepatic and renal fructose-1,6-diphosphatase and glucose-6-phosphatase increased markedly on fasting. Refeeding for four days after a four-day fast returned these enzyme activities to near control values.", "contents": "Effect of fasting and fasting and refeeding on hepatic and renal gluconeogenic enzymes in the chicken. The effect of fasting and fasting and refeeding on hepatic and renal gluconeogenic enzyme activities were studied in six-week-old chickens (Gallus domesticus: New Hampshire male x Columbian female). Hepatic pyruvate carboxylase appeared not to be affected by fasting, but the renal enzyme activity increased in four-day fasted chickens. The hepatic mitochondrial and cytosolic phosphoenolpyruvate carboxykinases were essentially not affected by fasting. The renal mitochondrial phosphoenolpyruvate carboxykinase showed a slight increase in activity only after a four-day fast, but the cytosolic enzyme activity increased markedly already after a two-day fast. Also the activities of the hepatic and renal fructose-1,6-diphosphatase and glucose-6-phosphatase increased markedly on fasting. Refeeding for four days after a four-day fast returned these enzyme activities to near control values."}
{"id": "PMID:226949", "title": "Detection of experimental carotid ulceration by radionucleotide labelled particles.", "content": "An animal model has been set up to study the adherence of various radionucleotide particles to experimental carotid ulcers. 6 animals were used in all, 4 dogs and 2 sheep. Carotid angiography was performed in 2 animals and in 1 of these the conventional mode of angiography failed to detect the carotid ulcer. Intra-arterial injection of technetium labelled macroaggregates in both of these cases showed the position of the lesion in vitro. In the remaining 4 cases, intravenous radionucleotide 99m technetium labelled pyrophosphate was used and in all cases in vitro the position of the experimental carotid ulceration was revealed. Our studies show that both technetium labelled macroaggregates and technetium labelled pyrophosphate are suitable particles for use in this model. Further research is required to establish the mode of their adherence to the experimental area of ulceration. A further extension of this work would be to demonstrate the ulceration in vivo. Encouraging work in this regard has been done by Mettinger et al. (1978) in humans demonstrating, by substraction methods, increased uptake over ulcerated carotid plaques as compared to controls.", "contents": "Detection of experimental carotid ulceration by radionucleotide labelled particles. An animal model has been set up to study the adherence of various radionucleotide particles to experimental carotid ulcers. 6 animals were used in all, 4 dogs and 2 sheep. Carotid angiography was performed in 2 animals and in 1 of these the conventional mode of angiography failed to detect the carotid ulcer. Intra-arterial injection of technetium labelled macroaggregates in both of these cases showed the position of the lesion in vitro. In the remaining 4 cases, intravenous radionucleotide 99m technetium labelled pyrophosphate was used and in all cases in vitro the position of the experimental carotid ulceration was revealed. Our studies show that both technetium labelled macroaggregates and technetium labelled pyrophosphate are suitable particles for use in this model. Further research is required to establish the mode of their adherence to the experimental area of ulceration. A further extension of this work would be to demonstrate the ulceration in vivo. Encouraging work in this regard has been done by Mettinger et al. (1978) in humans demonstrating, by substraction methods, increased uptake over ulcerated carotid plaques as compared to controls."}
{"id": "PMID:226950", "title": "The contribution of evoked potentials in the functional assessment of the somatosensory pathway.", "content": "The value of evoked potentials in studying conduction in the somatosensory pathway was assessed in patients with various neurological disorders. In patients with multiple sclerosis (MS) abnormalities of the cervical response (N14) were found particularly in longstanding cases but also in the early stages of the disease, even in patients without sensory symptoms or signs, and were reversible in some patients. The cortical response was also abnormal in some cases but the two were not always affected together. In Friedreich's ataxia both the cervical and cortical responses were usually abnormal. Subclinical abnormalities of the cervical responses were found in some patients with hereditary spastic paraparesis or mixed forms of spinocerebellar ataxia. The cervical responses were also abnormal in patients with peripheral neuropathy and cervical radiculopathy, and in some patients with brain-stem or thalamic lesions. Cervical and cortical responses were normal in the lateral medullary syndrome, whereas the cortical response was markedly abnormal in patients with high brain-stem or cerebral hemisphere vascular lesions. Cortical and subcortical responses were abnormal in some patients with stereotactic thalamic lesions. Enhanced cortical responses were found in patients with lesions at different levels in the CNS. The most marked enhancement was observed in patients with familial myoclonic epilepsy. Lesser degrees were found in some patients with MS, progressive supranuclear palsy, thalamic lesions, brain-stem encephalitis and syringomyelia. Enhanced responses were usually found in patients with minimal or no clinical sensory involvement. It is postulated that this type of abnormality results from an interference to the inhibitory mechanisms which normally operate at various levels in the somatosensory pathway. It is concluded that evoked potential studies are a valuable adjunct to the clinical evaluation of sensation, and that they may provide useful information on the pathophysiology of conduction in the somatosensory pathway.", "contents": "The contribution of evoked potentials in the functional assessment of the somatosensory pathway. The value of evoked potentials in studying conduction in the somatosensory pathway was assessed in patients with various neurological disorders. In patients with multiple sclerosis (MS) abnormalities of the cervical response (N14) were found particularly in longstanding cases but also in the early stages of the disease, even in patients without sensory symptoms or signs, and were reversible in some patients. The cortical response was also abnormal in some cases but the two were not always affected together. In Friedreich's ataxia both the cervical and cortical responses were usually abnormal. Subclinical abnormalities of the cervical responses were found in some patients with hereditary spastic paraparesis or mixed forms of spinocerebellar ataxia. The cervical responses were also abnormal in patients with peripheral neuropathy and cervical radiculopathy, and in some patients with brain-stem or thalamic lesions. Cervical and cortical responses were normal in the lateral medullary syndrome, whereas the cortical response was markedly abnormal in patients with high brain-stem or cerebral hemisphere vascular lesions. Cortical and subcortical responses were abnormal in some patients with stereotactic thalamic lesions. Enhanced cortical responses were found in patients with lesions at different levels in the CNS. The most marked enhancement was observed in patients with familial myoclonic epilepsy. Lesser degrees were found in some patients with MS, progressive supranuclear palsy, thalamic lesions, brain-stem encephalitis and syringomyelia. Enhanced responses were usually found in patients with minimal or no clinical sensory involvement. It is postulated that this type of abnormality results from an interference to the inhibitory mechanisms which normally operate at various levels in the somatosensory pathway. It is concluded that evoked potential studies are a valuable adjunct to the clinical evaluation of sensation, and that they may provide useful information on the pathophysiology of conduction in the somatosensory pathway."}
{"id": "PMID:226953", "title": "Affinity labeling of the catalytic subunit of cyclic AMP-dependent protein kinase by N alpha-tosyl-L-lysine chloromethyl ketone.", "content": "The catalytic subunit of cyclic AMP-dependent protein kinase (from rabbit skeletal muscle; ATP:protein phosphotransferase, EC 2.7.1.37) was found to be irreversibly inactivated by chloromethyl ketone derivatives of lysine and phenylalanine, chemical reagents originally designed for labeling the active sites of the proteolytic enzymes trypsin and chymotrypsin. This inactivation was shown to occur at pH 7.5 and 22 degrees C, conditions under which chemically related alkylating reagents such as chloroacetamide and chloroacetic acid (which do not possess the amino acid side chain) fail to inactivate the enzyme. In the case of the chloromethyl ketone derivative of N alpha-tosyl-L-lysine, the enzyme could be protected by its nucleotide substrate (MgATP), by one of its protein substrates (histone H2b), and by its regulatory subunit which, upon binding, shields the active site of the catalytic subunit. Differential labeling experiments, together with kinetic studies of the rates of modification of the sulfhydryl groups in the enzyme before and after inactivation with the chloromethyl ketone, suggest that the loss of activity is associated with one (kinetically characterized) sulfhydryl group present either at the active site of the enzyme or at a site intimately associated with it. The general implications of these results regarding the interpretation of affinity labeling experiments carried out in complex mixtures of proteins or under in vivo conditions are discussed.", "contents": "Affinity labeling of the catalytic subunit of cyclic AMP-dependent protein kinase by N alpha-tosyl-L-lysine chloromethyl ketone. The catalytic subunit of cyclic AMP-dependent protein kinase (from rabbit skeletal muscle; ATP:protein phosphotransferase, EC 2.7.1.37) was found to be irreversibly inactivated by chloromethyl ketone derivatives of lysine and phenylalanine, chemical reagents originally designed for labeling the active sites of the proteolytic enzymes trypsin and chymotrypsin. This inactivation was shown to occur at pH 7.5 and 22 degrees C, conditions under which chemically related alkylating reagents such as chloroacetamide and chloroacetic acid (which do not possess the amino acid side chain) fail to inactivate the enzyme. In the case of the chloromethyl ketone derivative of N alpha-tosyl-L-lysine, the enzyme could be protected by its nucleotide substrate (MgATP), by one of its protein substrates (histone H2b), and by its regulatory subunit which, upon binding, shields the active site of the catalytic subunit. Differential labeling experiments, together with kinetic studies of the rates of modification of the sulfhydryl groups in the enzyme before and after inactivation with the chloromethyl ketone, suggest that the loss of activity is associated with one (kinetically characterized) sulfhydryl group present either at the active site of the enzyme or at a site intimately associated with it. The general implications of these results regarding the interpretation of affinity labeling experiments carried out in complex mixtures of proteins or under in vivo conditions are discussed."}
{"id": "PMID:226954", "title": "Sequence heterogeneity at the 5' termini of late simian virus 40 19S and 16S mRNAs.", "content": "The 5'-cap-containing leader sequence of the most abundant 19S and 16S mRNAs of simian virus 40 (SV40) was previously mapped between 0.67 and 0.76 map units. We now find that the two late mRNA species contain multiple 5' ends. Eight different RNase T2-resistant cap structures were identified:m7GpppmAmpU (47%); m7GpppmAmpUmpU (19%); m7GpppmAmpC (16%); m7GpppmAmpCmpA (5%); m7GpppmAmpG (6%); m7GpppGmpC (3%); m7GpppmAmGmpA (2%); m7GpppGmpCmpG (2%). Capped T1 oligonucleotides of 19S and 16S mRNAs have been isolated by two different procedures: (i) chromatography on a DEAE-cellulose column followed by paper electrophoresis and (ii) two-dimensional electrophoresis/homochromatography. Cap structures of the isolated 5' oligonucleotides were identified. Each of the major caps was found to be associated with a few differential 5' oligonucleotides, implying a vast heterogeneity at the termini of SV40 late mRNAs. The results suggest that on SV40 DNA, RNA polymerase II has a reportoire of initiation points. In most of the cases, initiation takes place with adenosine triphosphate followed by a pyrimidine. Alternatively, transcription may start at one specific point but a unique mechanism of processing generates heterogeneous populations of termini with a common 5' adenosine triphosphate.", "contents": "Sequence heterogeneity at the 5' termini of late simian virus 40 19S and 16S mRNAs. The 5'-cap-containing leader sequence of the most abundant 19S and 16S mRNAs of simian virus 40 (SV40) was previously mapped between 0.67 and 0.76 map units. We now find that the two late mRNA species contain multiple 5' ends. Eight different RNase T2-resistant cap structures were identified:m7GpppmAmpU (47%); m7GpppmAmpUmpU (19%); m7GpppmAmpC (16%); m7GpppmAmpCmpA (5%); m7GpppmAmpG (6%); m7GpppGmpC (3%); m7GpppmAmGmpA (2%); m7GpppGmpCmpG (2%). Capped T1 oligonucleotides of 19S and 16S mRNAs have been isolated by two different procedures: (i) chromatography on a DEAE-cellulose column followed by paper electrophoresis and (ii) two-dimensional electrophoresis/homochromatography. Cap structures of the isolated 5' oligonucleotides were identified. Each of the major caps was found to be associated with a few differential 5' oligonucleotides, implying a vast heterogeneity at the termini of SV40 late mRNAs. The results suggest that on SV40 DNA, RNA polymerase II has a reportoire of initiation points. In most of the cases, initiation takes place with adenosine triphosphate followed by a pyrimidine. Alternatively, transcription may start at one specific point but a unique mechanism of processing generates heterogeneous populations of termini with a common 5' adenosine triphosphate."}
{"id": "PMID:226955", "title": "Cellular information in the genome of recovered avian sarcoma virus directs the synthesis of transforming protein.", "content": "Recovered avian sarcoma viruses, whose sarcomagenic information is largely derived from cellular sequences [Wang, L.-H., Halpern, C.C., Nadel, M. & Hanafusa, H. (1978) Proc. Natl. Acad. Sci. USA 75, 5812-5816], produce the transforming protein p60src in infected cells, in amounts comparable to the amount found in cells transformed by standard strains of avian sarcoma virus. Though displaying some virus-specific differences in electrophoretic mobility, p60srcs from these viruses are similar to those of other avian sarcoma virus strains by the criteria of (i) antigenicity, (ii) partial proteolysis mapping, and (iii) association with protein kinase activity. We also find that p60sarc, a protein present in normal cells at a low level, is associated with a protein kinase activity, and thus it too is similar by the above criteria to p60src of avian sarcoma virus. Possible causes for the pathogenicity of p60src are discussed in light of these similarities.", "contents": "Cellular information in the genome of recovered avian sarcoma virus directs the synthesis of transforming protein. Recovered avian sarcoma viruses, whose sarcomagenic information is largely derived from cellular sequences [Wang, L.-H., Halpern, C.C., Nadel, M. & Hanafusa, H. (1978) Proc. Natl. Acad. Sci. USA 75, 5812-5816], produce the transforming protein p60src in infected cells, in amounts comparable to the amount found in cells transformed by standard strains of avian sarcoma virus. Though displaying some virus-specific differences in electrophoretic mobility, p60srcs from these viruses are similar to those of other avian sarcoma virus strains by the criteria of (i) antigenicity, (ii) partial proteolysis mapping, and (iii) association with protein kinase activity. We also find that p60sarc, a protein present in normal cells at a low level, is associated with a protein kinase activity, and thus it too is similar by the above criteria to p60src of avian sarcoma virus. Possible causes for the pathogenicity of p60src are discussed in light of these similarities."}
{"id": "PMID:226956", "title": "A normal cell protein similar in structure and function to the avian sarcoma virus transforming gene product.", "content": "This report extends our previous studies concerning the identification and characterization of a protein from normal cells that is closely related to the avian sarcoma virus (ASV) transforming gene product pp60src. This normal cellular protein, which we have found in both avian and mammalian cells and have tentatively designated pp60sarc, was detected by immunoprecipitation of radiolabeled cell extracts with serum derived from both mice and rabbits bearing ASV-induced tumors. The normal cell pp60sarc is a 60,000-dalton phosphoprotein that is structurally similar, but not identical, to viral pp60src. The phosphorylation patterns of the normal cell and viral proteins are also similar: both contain two major phosphorylated residues, a phosphoserine located on the NH2-terminal 60% of the polypeptide and a phosphothreonine present on the COOH-terminal 40% of the molecule. In addition, the normal cell pp60sarc from both chicken and mammalian cells appears to have an associated protein kinase activity analogous to that previously described for the viral pp60src. The possible roles played by the normal cell protein pp60sarc and the ASV transforming protein pp60src in normal cellular growth and neoplastic disease, respectively, are discussed.", "contents": "A normal cell protein similar in structure and function to the avian sarcoma virus transforming gene product. This report extends our previous studies concerning the identification and characterization of a protein from normal cells that is closely related to the avian sarcoma virus (ASV) transforming gene product pp60src. This normal cellular protein, which we have found in both avian and mammalian cells and have tentatively designated pp60sarc, was detected by immunoprecipitation of radiolabeled cell extracts with serum derived from both mice and rabbits bearing ASV-induced tumors. The normal cell pp60sarc is a 60,000-dalton phosphoprotein that is structurally similar, but not identical, to viral pp60src. The phosphorylation patterns of the normal cell and viral proteins are also similar: both contain two major phosphorylated residues, a phosphoserine located on the NH2-terminal 60% of the polypeptide and a phosphothreonine present on the COOH-terminal 40% of the molecule. In addition, the normal cell pp60sarc from both chicken and mammalian cells appears to have an associated protein kinase activity analogous to that previously described for the viral pp60src. The possible roles played by the normal cell protein pp60sarc and the ASV transforming protein pp60src in normal cellular growth and neoplastic disease, respectively, are discussed."}
{"id": "PMID:226957", "title": "Cell-free translation and thyroxine induction of carbamyl phosphate synthetase I messenger RNA in tadpole liver.", "content": "Total RNA of tadpole and frog (Rana catesbeiana) liver was isolated by either 7 or 8 M guanidine . HCl extraction and translated in a cell-free protein-synthesizing system derived from rabbit reticulocytes. The identity of carbamyl phosphate synthetase I[carbamoyl-phosphate synthase (ammonia); ATP:carbamate phosphotransferase (dephosphorylating), EC 2.7.2.5] synthesized in vitro with the purified enzyme was established as follows: (i) immunoprecipitation by a specific antibody; (i) comigration with purified carrier enzyme on sodium dodecyl sulfate/polyacrylamide gel electrophoresis; (iii) copurification with carrier enzyme by affinity chromatography on Cibacron Blue F3GA-coupled agarose; and (iv) formation of identical proteolytic cleavage products. Inclusion of protease inhibitors in the system resulted in no apparent change in the polypeptide molecular weight. These results indicate that carbamyl phosphate synthetase I is synthesized as a polypeptide that is indistinguishable from the mature enzyme by the analytical methods used and that it is not grossly modified during its transport into mitochondria. The level of translatable mRNA for carbamyl phosphate synthetase-I in tadpole liver was increased about 2-fold 1 day after thyroxine treatment and did not change significantly through 4 subsequent days of treatment. Thus the thyroxine-induced synthesis of carbamyl phosphate synthetase I in tadpole liver is at least partly due to an increase of translatable mRNA for this enzyme.", "contents": "Cell-free translation and thyroxine induction of carbamyl phosphate synthetase I messenger RNA in tadpole liver. Total RNA of tadpole and frog (Rana catesbeiana) liver was isolated by either 7 or 8 M guanidine . HCl extraction and translated in a cell-free protein-synthesizing system derived from rabbit reticulocytes. The identity of carbamyl phosphate synthetase I[carbamoyl-phosphate synthase (ammonia); ATP:carbamate phosphotransferase (dephosphorylating), EC 2.7.2.5] synthesized in vitro with the purified enzyme was established as follows: (i) immunoprecipitation by a specific antibody; (i) comigration with purified carrier enzyme on sodium dodecyl sulfate/polyacrylamide gel electrophoresis; (iii) copurification with carrier enzyme by affinity chromatography on Cibacron Blue F3GA-coupled agarose; and (iv) formation of identical proteolytic cleavage products. Inclusion of protease inhibitors in the system resulted in no apparent change in the polypeptide molecular weight. These results indicate that carbamyl phosphate synthetase I is synthesized as a polypeptide that is indistinguishable from the mature enzyme by the analytical methods used and that it is not grossly modified during its transport into mitochondria. The level of translatable mRNA for carbamyl phosphate synthetase-I in tadpole liver was increased about 2-fold 1 day after thyroxine treatment and did not change significantly through 4 subsequent days of treatment. Thus the thyroxine-induced synthesis of carbamyl phosphate synthetase I in tadpole liver is at least partly due to an increase of translatable mRNA for this enzyme."}
{"id": "PMID:226958", "title": "Coupling of the glucagon receptor to adenylyl cyclase by GDP: evidence for two levels of regulation of adenylyl cyclase.", "content": "In rat liver plasma membranes preactivated with guanosine 5'-[beta,gamma-imido[triphosphate (GuoPP[NH]P), GDP promoted coupling of occupied glucagon receptor to adenylyl cyclase [adenylate cyclase; ATP, pyrophosphate-lyase (cyclizing), EC 4.6.1.1] with an apparent association constant Ka of 0.1-0.15 microM. The apparent Ka for the same effect of GTP was 0.2 microM. The effect of GDP was shown not to be due to GTP formed by putative transphosphorylation reaction(s) when ATP was present in the assay as substrate. In membranes not preactivated with GuoPP[NH]P, GDP both competitively inhibited GuoPP[NH]P stimulation of adenylyl cyclase (Ki 0.10 microM) and supported stimulation of cyclizing activity (apparent Ka 0.10 microM) by glucagon. These effects of GDP occurred in the absence of added GTP and in the absence of sufficient formation of GTP by putative transphosphorylation reaction(s) to account for them. It is concluded that two levels of regulation of liver adenylyl cyclase (cyclizing) activity must exit. One level is termed \"receptor regulation\"; it depends on occupancy of a receptor-related R site by nucleotide and is specific for either GDP or GTP. The second level of regulation is termed \"GTPase regulation\"; it is inhibited by GDP, depends on both GTP and GTPase, and accounts for activation of cyclizing activity by nonhydrolyzable analogs of GTP. The data suggest that both levels of regulation coexist and may synergize, one mediating responses to stimuli external to the cell (receptor regulation) and the other mediating stimuli of intracellular origin (GTPase regulation).", "contents": "Coupling of the glucagon receptor to adenylyl cyclase by GDP: evidence for two levels of regulation of adenylyl cyclase. In rat liver plasma membranes preactivated with guanosine 5'-[beta,gamma-imido[triphosphate (GuoPP[NH]P), GDP promoted coupling of occupied glucagon receptor to adenylyl cyclase [adenylate cyclase; ATP, pyrophosphate-lyase (cyclizing), EC 4.6.1.1] with an apparent association constant Ka of 0.1-0.15 microM. The apparent Ka for the same effect of GTP was 0.2 microM. The effect of GDP was shown not to be due to GTP formed by putative transphosphorylation reaction(s) when ATP was present in the assay as substrate. In membranes not preactivated with GuoPP[NH]P, GDP both competitively inhibited GuoPP[NH]P stimulation of adenylyl cyclase (Ki 0.10 microM) and supported stimulation of cyclizing activity (apparent Ka 0.10 microM) by glucagon. These effects of GDP occurred in the absence of added GTP and in the absence of sufficient formation of GTP by putative transphosphorylation reaction(s) to account for them. It is concluded that two levels of regulation of liver adenylyl cyclase (cyclizing) activity must exit. One level is termed \"receptor regulation\"; it depends on occupancy of a receptor-related R site by nucleotide and is specific for either GDP or GTP. The second level of regulation is termed \"GTPase regulation\"; it is inhibited by GDP, depends on both GTP and GTPase, and accounts for activation of cyclizing activity by nonhydrolyzable analogs of GTP. The data suggest that both levels of regulation coexist and may synergize, one mediating responses to stimuli external to the cell (receptor regulation) and the other mediating stimuli of intracellular origin (GTPase regulation)."}
{"id": "PMID:226959", "title": "Cyclic AMP as a modulator of polarity in polycistronic transcriptional units.", "content": "The degree of natural polarity in the lactose and galactose operons of Escherichia coli is affected by adenosine 3',5'-cyclic monophosphate (cAMP). This effect, mediated by the cAMP receptor protein, is exerted at sites distinct from the promoter. Experiments performed with a mutant bearing a thermosensitive rho factor activity indicate that cAMP relieves polarity by interfering with transcription termination. Conflicting results in the literature concerning the role of cAMP receptor protein and cAMP in galactose operon expression can be reconciled by the findings that cAMP stimulates the expression of operator distal genes without significantly affecting the proximal genes. Therefore, it appears necessary to reevaluate the classification of the galactose operon as exhibiting cAMP-mediated catabolite repression at the level of transcription initiation.", "contents": "Cyclic AMP as a modulator of polarity in polycistronic transcriptional units. The degree of natural polarity in the lactose and galactose operons of Escherichia coli is affected by adenosine 3',5'-cyclic monophosphate (cAMP). This effect, mediated by the cAMP receptor protein, is exerted at sites distinct from the promoter. Experiments performed with a mutant bearing a thermosensitive rho factor activity indicate that cAMP relieves polarity by interfering with transcription termination. Conflicting results in the literature concerning the role of cAMP receptor protein and cAMP in galactose operon expression can be reconciled by the findings that cAMP stimulates the expression of operator distal genes without significantly affecting the proximal genes. Therefore, it appears necessary to reevaluate the classification of the galactose operon as exhibiting cAMP-mediated catabolite repression at the level of transcription initiation."}
{"id": "PMID:226960", "title": "Structure of the antithrombin-binding site in heparin.", "content": "Heparin preparations from pig intestinal mucosa and from bovine lung were separated by chromatography on antithrombin-Sepharose into a high-affinity fraction (with high anticoagulant activity) and a low-affinity fraction (with low anticoagulant). Antithrombin-binding heparin fragments (12-16 monosaccharide units) were prepared, either by digesting a high-affinity heparin-antithrombin complex with bacterial heparinase or by partial deaminative cleavage of the unfractionated polysaccharide with nitrous acid followed by affinity chromatography on immobilized antithrombin. Compositional analysis based on separation and identification of deamination products reduced with sodium boro[3H]hydride showed that nonsulfated L-iduronic acid occurred in larger amounts in high-affinity heparin than in low-affinity heparin; furthermore, this component was concentrated in the antithrombin-binding regions of the high-affinity heparin molecules, amounting to approximately one residue per binding site. It is suggested that nonsulfated L-iduronic acid is essential for the anticoagulant activity of heparin. The location of the non-sulfated uronic acid in the antithrombin-binding site was determined by periodate oxidation of antithrombin-binding fragments containing a terminal 2,5-anhydro-D-[1-3H]mannitol unit. Tentative structures for antithrombin-binding sequences in heparin are proposed, including some structural variants believed to be compatible with, but not required for, activity.", "contents": "Structure of the antithrombin-binding site in heparin. Heparin preparations from pig intestinal mucosa and from bovine lung were separated by chromatography on antithrombin-Sepharose into a high-affinity fraction (with high anticoagulant activity) and a low-affinity fraction (with low anticoagulant). Antithrombin-binding heparin fragments (12-16 monosaccharide units) were prepared, either by digesting a high-affinity heparin-antithrombin complex with bacterial heparinase or by partial deaminative cleavage of the unfractionated polysaccharide with nitrous acid followed by affinity chromatography on immobilized antithrombin. Compositional analysis based on separation and identification of deamination products reduced with sodium boro[3H]hydride showed that nonsulfated L-iduronic acid occurred in larger amounts in high-affinity heparin than in low-affinity heparin; furthermore, this component was concentrated in the antithrombin-binding regions of the high-affinity heparin molecules, amounting to approximately one residue per binding site. It is suggested that nonsulfated L-iduronic acid is essential for the anticoagulant activity of heparin. The location of the non-sulfated uronic acid in the antithrombin-binding site was determined by periodate oxidation of antithrombin-binding fragments containing a terminal 2,5-anhydro-D-[1-3H]mannitol unit. Tentative structures for antithrombin-binding sequences in heparin are proposed, including some structural variants believed to be compatible with, but not required for, activity."}
{"id": "PMID:226961", "title": "Theoretical methods for study of kinetics of models of the mitochondrial respiratory chain.", "content": "In earlier work, Hill and Chance obtained exact steady-state kinetic properties for partial models of the mitochondrial respiratory chain with two isopotential pools and one four-state \"site enzyme\" between the two pools. That work is extended here to full models of the respiratory chain with four isopotential pools and three four-state site enzymes between pairs of pools. Because of the complexity of the model, exact calculations are no longer possible. Instead, we show, by means of some examples, the feasibility of using Monte Carlo calculations on all cases and numerical solution of thousands of kinetic differential equations in many cases.", "contents": "Theoretical methods for study of kinetics of models of the mitochondrial respiratory chain. In earlier work, Hill and Chance obtained exact steady-state kinetic properties for partial models of the mitochondrial respiratory chain with two isopotential pools and one four-state \"site enzyme\" between the two pools. That work is extended here to full models of the respiratory chain with four isopotential pools and three four-state site enzymes between pairs of pools. Because of the complexity of the model, exact calculations are no longer possible. Instead, we show, by means of some examples, the feasibility of using Monte Carlo calculations on all cases and numerical solution of thousands of kinetic differential equations in many cases."}
{"id": "PMID:226962", "title": "Kinetics of the induction of three translation-regulatory enzymes by interferon.", "content": "Three enzymes that cause inhibition of mRNA translation, eukaryotic initiation factor 2 protein kinase PK-i, oligoisoadenylate synthetase E, and phosphodiesterase 2'-PDi, have been recently isolated from interferon-treated cells. We show that the rise in these three enzyme activities may be used to study the response of uninfected cells to interferon. For each enzyme, a specific microassay that can be carried out on extracts from 2-5 x 10(4) monolayer cells from mouse, monkey, or man was developed. With these assays, the kinetics of induction of the three enzymes in mouse L cells are compared. The dose dependence for protein kinase PK-i induction is shown to be similar to that for the development of the antiviral state. Actinomycin D and anti-interferon serum block enzyme induction if added to the cells early after interferon treatment. The quantitative measurements of the intracellular level of these enzymes provide a new and convenient model to study the cell's response to interferon.", "contents": "Kinetics of the induction of three translation-regulatory enzymes by interferon. Three enzymes that cause inhibition of mRNA translation, eukaryotic initiation factor 2 protein kinase PK-i, oligoisoadenylate synthetase E, and phosphodiesterase 2'-PDi, have been recently isolated from interferon-treated cells. We show that the rise in these three enzyme activities may be used to study the response of uninfected cells to interferon. For each enzyme, a specific microassay that can be carried out on extracts from 2-5 x 10(4) monolayer cells from mouse, monkey, or man was developed. With these assays, the kinetics of induction of the three enzymes in mouse L cells are compared. The dose dependence for protein kinase PK-i induction is shown to be similar to that for the development of the antiviral state. Actinomycin D and anti-interferon serum block enzyme induction if added to the cells early after interferon treatment. The quantitative measurements of the intracellular level of these enzymes provide a new and convenient model to study the cell's response to interferon."}
{"id": "PMID:226963", "title": "Binding characteristics and apparent molecular size of detergent solubilized nerve growth factor receptor of sympathetic ganglia.", "content": "Nerve growth factor (NGF), a hormone-like regulator of sympathetic neuron ontogeny and metabolism affects its target cells initially by associating with specific plasma membrane receptors. We have solubilized the NGF receptor of adult rabbit superior cervical ganglia (SCG) with the nonionic detergent Triton X-100. The high-affinity equilibrium binding constant of the detergent-extracted receptor is 2-8 x 10(-10) M. Gel chromatography of the receptor or the 125I-labeled NGF receptor complex on a column of Sepharose 6B indicated, in both cases, a single component of an apparent hydrodynamic radius of 71 +/- 5 A. In parallel investigations, we have confirmed the similarity between the hydrodynamic size of the NGF receptor of rabbit SCG and that of the insulin receptor of IM-9 lymphocytes evaluated by similar methods.", "contents": "Binding characteristics and apparent molecular size of detergent solubilized nerve growth factor receptor of sympathetic ganglia. Nerve growth factor (NGF), a hormone-like regulator of sympathetic neuron ontogeny and metabolism affects its target cells initially by associating with specific plasma membrane receptors. We have solubilized the NGF receptor of adult rabbit superior cervical ganglia (SCG) with the nonionic detergent Triton X-100. The high-affinity equilibrium binding constant of the detergent-extracted receptor is 2-8 x 10(-10) M. Gel chromatography of the receptor or the 125I-labeled NGF receptor complex on a column of Sepharose 6B indicated, in both cases, a single component of an apparent hydrodynamic radius of 71 +/- 5 A. In parallel investigations, we have confirmed the similarity between the hydrodynamic size of the NGF receptor of rabbit SCG and that of the insulin receptor of IM-9 lymphocytes evaluated by similar methods."}
{"id": "PMID:226964", "title": "Presence of free cyclic AMP receptor protein and regulation of its level by cyclic AMP in neuroblastoma-glioma hybrid cells.", "content": "Neuroblastoma-glioma hybrid cells of line 108CC-5 were found to contain high levels of soluble adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase activity and high levels of two specific cAMP receptor proteins, RI and RII. Treatment of the hybrid cells with dibutyryl cAMP increased the level of RI but did not significantly affect the level either of RII or of cAMP-dependent protein kinase activity. The effect of dibutyryl cAMP could be mimicked by prostaglandin E1 and 3-isobutyl-1-methylxanthine, both of which are known to raise cAMP levels in neuroblastoma-glioma hybrid cells. Both in control as well as in dibutyryl cAMP-treated cells, RII but not RI was associated with cAMP-dependent protein kinase. Several lines of evidence suggest that RI represents the free regulatory subunit of type I cAMP-dependent protein kinase. The presence of this regulatory subunit as free cAMP receptor protein in neuroblastoma-glioma hybrid cells may be of significance with respect to the regulation of growth and differentiation in tumor cells.", "contents": "Presence of free cyclic AMP receptor protein and regulation of its level by cyclic AMP in neuroblastoma-glioma hybrid cells. Neuroblastoma-glioma hybrid cells of line 108CC-5 were found to contain high levels of soluble adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase activity and high levels of two specific cAMP receptor proteins, RI and RII. Treatment of the hybrid cells with dibutyryl cAMP increased the level of RI but did not significantly affect the level either of RII or of cAMP-dependent protein kinase activity. The effect of dibutyryl cAMP could be mimicked by prostaglandin E1 and 3-isobutyl-1-methylxanthine, both of which are known to raise cAMP levels in neuroblastoma-glioma hybrid cells. Both in control as well as in dibutyryl cAMP-treated cells, RII but not RI was associated with cAMP-dependent protein kinase. Several lines of evidence suggest that RI represents the free regulatory subunit of type I cAMP-dependent protein kinase. The presence of this regulatory subunit as free cAMP receptor protein in neuroblastoma-glioma hybrid cells may be of significance with respect to the regulation of growth and differentiation in tumor cells."}
{"id": "PMID:226965", "title": "beta-Endorphin: synthesis of analogs modified at the carboxyl terminus with increased activites.", "content": "Three analogs of human beta-endorphin (beta h-EP) have been synthesized: [Gly31]beta h-EP, [Gly31]beta h-endorphinamide, and [Gly31]beta h-endorphinylglycine. All are more active than beta h-EP in both the guinea pig ileum bioassay and the opiate receptor binding assay. The last two analogs are about twice as active as beta h-EP in an assay for analgesia. Modification at position 31 and extension at the COOH terminus may afford a route toward analogs with even greater biological activity.", "contents": "beta-Endorphin: synthesis of analogs modified at the carboxyl terminus with increased activites. Three analogs of human beta-endorphin (beta h-EP) have been synthesized: [Gly31]beta h-EP, [Gly31]beta h-endorphinamide, and [Gly31]beta h-endorphinylglycine. All are more active than beta h-EP in both the guinea pig ileum bioassay and the opiate receptor binding assay. The last two analogs are about twice as active as beta h-EP in an assay for analgesia. Modification at position 31 and extension at the COOH terminus may afford a route toward analogs with even greater biological activity."}
{"id": "PMID:226966", "title": "Differential sensitivity of gene expression in vitro to inhibitors of DNA gyrase.", "content": "We have used the antibiotics coumermycin A1, novobiocin, and oxolinic acid, which are specific inhibitors of DNA gyrase, to study the coupled transcription and translation of several bacterial and plasmid genes in a DNA-directed cell-free system. The expression of different genes is reduced to different extents by inhibition of DNA gyrase activity. Among the genes tested, the lac operon, an rRNA gene, and the colicin gene of colicin E1 plasmid were found to be most sensitive, while the trp operon and some other genes in colicin E1 plasmid were relatively unaffected by the inhibitors. These results, together with earlier work on the transcription of circular DNA templates, indicate that DNA supercoiling can significantly enhance transcription from certain promoters.", "contents": "Differential sensitivity of gene expression in vitro to inhibitors of DNA gyrase. We have used the antibiotics coumermycin A1, novobiocin, and oxolinic acid, which are specific inhibitors of DNA gyrase, to study the coupled transcription and translation of several bacterial and plasmid genes in a DNA-directed cell-free system. The expression of different genes is reduced to different extents by inhibition of DNA gyrase activity. Among the genes tested, the lac operon, an rRNA gene, and the colicin gene of colicin E1 plasmid were found to be most sensitive, while the trp operon and some other genes in colicin E1 plasmid were relatively unaffected by the inhibitors. These results, together with earlier work on the transcription of circular DNA templates, indicate that DNA supercoiling can significantly enhance transcription from certain promoters."}
{"id": "PMID:226967", "title": "Structure of cytochrome a3-Cua3 couple in cytochrome c oxidase as revealed by nitric oxide binding studies.", "content": "The addition of NO to oxidized cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1) causes the appearance of a high-spin heme electron paramagnetic resonance (EPR) signal due to cytochrome a3. This suggests that NO coordinates to Cu+2a3 and breaks the antiferromagnetic couple by forming a cytochrome a+33-Cu+2a3-NO complex. The intensity of the high-spin cytochrome a3 signal depends on the method of preparation of the enzyme and maximally accounts for 58% of one heme. The effect of N-3 on the cytochrome a+33-Cu+2a3-NO complex is to reduce cytochrome a3 to the ferrous state, and this is followed by formation of a new complex that exhibits EPR signals characteristic of a triplet species. On the basis of optical and EPR results, a NO bridge between cytochrome a+23 and Cu+2a3 is proposed--i.e., cytochrome a+23-NO-Cu+2a3. The half-field transition observed at g = 4.34 in the EPR spectrum of this triplet species exhibits resolved copper hyperfine splittings with [A+2] = 0.020 cm-1, indicating that the Cu+2a3 in the cytochrome a+23-NO-Cu+2a3 complex is similar to a type 2 copper site.", "contents": "Structure of cytochrome a3-Cua3 couple in cytochrome c oxidase as revealed by nitric oxide binding studies. The addition of NO to oxidized cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1) causes the appearance of a high-spin heme electron paramagnetic resonance (EPR) signal due to cytochrome a3. This suggests that NO coordinates to Cu+2a3 and breaks the antiferromagnetic couple by forming a cytochrome a+33-Cu+2a3-NO complex. The intensity of the high-spin cytochrome a3 signal depends on the method of preparation of the enzyme and maximally accounts for 58% of one heme. The effect of N-3 on the cytochrome a+33-Cu+2a3-NO complex is to reduce cytochrome a3 to the ferrous state, and this is followed by formation of a new complex that exhibits EPR signals characteristic of a triplet species. On the basis of optical and EPR results, a NO bridge between cytochrome a+23 and Cu+2a3 is proposed--i.e., cytochrome a+23-NO-Cu+2a3. The half-field transition observed at g = 4.34 in the EPR spectrum of this triplet species exhibits resolved copper hyperfine splittings with [A+2] = 0.020 cm-1, indicating that the Cu+2a3 in the cytochrome a+23-NO-Cu+2a3 complex is similar to a type 2 copper site."}
{"id": "PMID:226968", "title": "Receptor-mediated endocytosis: insights from the lipoprotein receptor system.", "content": "The low density lipoprotein (LDL) receptor system coordinates the metabolism of cholesterol, an essential component of the plasma membrane of all mammalian cells. Study of this system has led to an enhanced understanding of the cellular basis of cholesterol homeostasis. It has also brought into focus an important mechanism of metabolic regulation--the process of receptor-mediated endocytosis. In this article, we first describe the receptor-mediated endocytosis of LDL, a sequence of events in which receptor binding and internalization are coupled in specialized regions of the plasma membrane called coated pits. Second, we trace the cellular functions of the cholesterol derived from internalized LDL. Third, genetic evidence is presented to indicate that both the binding and internalization of LDL are mediated by a single receptor molecule that contains two active sites, one mediating binding and the other internalization. Finally, the characteristics of the LDL receptor system are used to suggest models for receptor systems in general.", "contents": "Receptor-mediated endocytosis: insights from the lipoprotein receptor system. The low density lipoprotein (LDL) receptor system coordinates the metabolism of cholesterol, an essential component of the plasma membrane of all mammalian cells. Study of this system has led to an enhanced understanding of the cellular basis of cholesterol homeostasis. It has also brought into focus an important mechanism of metabolic regulation--the process of receptor-mediated endocytosis. In this article, we first describe the receptor-mediated endocytosis of LDL, a sequence of events in which receptor binding and internalization are coupled in specialized regions of the plasma membrane called coated pits. Second, we trace the cellular functions of the cholesterol derived from internalized LDL. Third, genetic evidence is presented to indicate that both the binding and internalization of LDL are mediated by a single receptor molecule that contains two active sites, one mediating binding and the other internalization. Finally, the characteristics of the LDL receptor system are used to suggest models for receptor systems in general."}
{"id": "PMID:226969", "title": "Increase of normal myeloblast viability and multiplication without blocking differentiation by type C RNA virus from myeloid leukemic cells.", "content": "Clones of mouse myeloid leukemic cells that differ in their competence to be induced for normal cell differentiation by the protein inducer MGI produce type C virus. These viruses have been studied for their effect on the viability, multiplication, and differentiation of normal bone marrow cells either with or without the addition of MGI. Virus from leukemic clones that can differentiate normally to mature macrophages and granulocytes (MGI+D+ clones) induced some multiplication of myeloblasts in the bone marrow, but the cells did not differentiate without adding MGI. In the presence of MGI, this virus then induced an increased number of colonies whose cells differentiated to mature macrophages or granulocytes as in colonies of uninfected cells. Virus infection also resulted in a decrease in the amount of MGI and fetal calf serum that was required for colony formation. Virus from MGI+D+ clones, in the presence of MGI, was 500-fold more effective in increasing colony formation than virus from the differentiation-defective MGI-D- clones, although both types of virus replicated with equal efficiency in the normal bone marrow cells. No such increase was obtained after infection with the Friend leukemic virus complex or the Moloney murine leukemia virus. Infection with virus from a MGI+D+ clone that was differentiated by MGI mainly to macrophages induced a higher percentage of macrophage colonies than virus from MGI+D+ clones that were differentiated by MGI to granulocytes and macrophages. Studies with isolated myeloblast colony-forming cells from the bone marrow have indicated that these are the target cells for the virus. Infections of these isolated myeloblasts with virus from MGI+D+ clones induced some multiplication without differentiation in the absence of MGI, and increased the viability and multiplication of the myeloblasts without inhibiting their ability to differentiate in the presence of MGI. The results, therefore, indicate that virus from MGI+D+ cells can increase the viability and multiplication of normal myeloblasts in the bone marrow without blocking the ability of these cells to be induced to differentiate by MGI, and that this effect was directly related to the competence of the leukemic host cells to be induced for normal differentiation. It is suggested that the difference between the effect of virus from MGI+D+ and MGI-D- cells may be due to a difference in their integration sites in relation to the genes that control cell viability, multiplication, and differentiation.", "contents": "Increase of normal myeloblast viability and multiplication without blocking differentiation by type C RNA virus from myeloid leukemic cells. Clones of mouse myeloid leukemic cells that differ in their competence to be induced for normal cell differentiation by the protein inducer MGI produce type C virus. These viruses have been studied for their effect on the viability, multiplication, and differentiation of normal bone marrow cells either with or without the addition of MGI. Virus from leukemic clones that can differentiate normally to mature macrophages and granulocytes (MGI+D+ clones) induced some multiplication of myeloblasts in the bone marrow, but the cells did not differentiate without adding MGI. In the presence of MGI, this virus then induced an increased number of colonies whose cells differentiated to mature macrophages or granulocytes as in colonies of uninfected cells. Virus infection also resulted in a decrease in the amount of MGI and fetal calf serum that was required for colony formation. Virus from MGI+D+ clones, in the presence of MGI, was 500-fold more effective in increasing colony formation than virus from the differentiation-defective MGI-D- clones, although both types of virus replicated with equal efficiency in the normal bone marrow cells. No such increase was obtained after infection with the Friend leukemic virus complex or the Moloney murine leukemia virus. Infection with virus from a MGI+D+ clone that was differentiated by MGI mainly to macrophages induced a higher percentage of macrophage colonies than virus from MGI+D+ clones that were differentiated by MGI to granulocytes and macrophages. Studies with isolated myeloblast colony-forming cells from the bone marrow have indicated that these are the target cells for the virus. Infections of these isolated myeloblasts with virus from MGI+D+ clones induced some multiplication without differentiation in the absence of MGI, and increased the viability and multiplication of the myeloblasts without inhibiting their ability to differentiate in the presence of MGI. The results, therefore, indicate that virus from MGI+D+ cells can increase the viability and multiplication of normal myeloblasts in the bone marrow without blocking the ability of these cells to be induced to differentiate by MGI, and that this effect was directly related to the competence of the leukemic host cells to be induced for normal differentiation. It is suggested that the difference between the effect of virus from MGI+D+ and MGI-D- cells may be due to a difference in their integration sites in relation to the genes that control cell viability, multiplication, and differentiation."}
{"id": "PMID:226970", "title": "Different rat-derived transforming retroviruses code for an immunologically related intracellular phosphoprotein.", "content": "Kirsten sarcoma virus (Ki-MSV) and Harvey sarcoma virus (Ha-MSV) are mouse-rat recombinant viruses that were originally isolated by experimental inoculation of rats with helper-independent mouse type C viruses. We have recently identified in cells transformed by Ki-MSV or Ha-MSV, a phosphoprotein, p21, coded for by Ki-MSV and Ha-MSV [Shih, T.Y., Weeks, M.O., Young, H.A. & Scolnick, E.M. (1979) Virology 95, in press]. The p21, which is not a virion structural protein, was identified with antisera prepared by transplantation in rats of syngeneic Ha-MSV- or Ki-MSV-transformed nonproducer cells. In this study, we have applied the same methodology to examine a purely rat sarcoma virus (RaSV), which was isolated in cell culture by using helper-independent rat type C viruses [Rasheed, S., Gardner, M.B. & Huebner, R.J. (1978) Proc. Natl. Acad. Sci. USA 75, 2972-2976]. We report here that this new, purely rat sarcoma virus apparently codes for a p29, which shares immunological determinants and common V-8 protease-generated peptides with the p21 of Ha-MSV. The data suggest that the RaSV has acquired genetic information with similar coding capacity to some rat genetic information with similar coding combinant viruses, Ki-MSV and Ha-MSV. Based on data obtained on the p21 of a mutant of Ki-MSV temperature-sensitive for the maintenance of transformation, we suggest that the gene in RaSV that codes for the p29 is also required for the maintenance of RaSV-induced fibroblast transformation.", "contents": "Different rat-derived transforming retroviruses code for an immunologically related intracellular phosphoprotein. Kirsten sarcoma virus (Ki-MSV) and Harvey sarcoma virus (Ha-MSV) are mouse-rat recombinant viruses that were originally isolated by experimental inoculation of rats with helper-independent mouse type C viruses. We have recently identified in cells transformed by Ki-MSV or Ha-MSV, a phosphoprotein, p21, coded for by Ki-MSV and Ha-MSV [Shih, T.Y., Weeks, M.O., Young, H.A. & Scolnick, E.M. (1979) Virology 95, in press]. The p21, which is not a virion structural protein, was identified with antisera prepared by transplantation in rats of syngeneic Ha-MSV- or Ki-MSV-transformed nonproducer cells. In this study, we have applied the same methodology to examine a purely rat sarcoma virus (RaSV), which was isolated in cell culture by using helper-independent rat type C viruses [Rasheed, S., Gardner, M.B. & Huebner, R.J. (1978) Proc. Natl. Acad. Sci. USA 75, 2972-2976]. We report here that this new, purely rat sarcoma virus apparently codes for a p29, which shares immunological determinants and common V-8 protease-generated peptides with the p21 of Ha-MSV. The data suggest that the RaSV has acquired genetic information with similar coding capacity to some rat genetic information with similar coding combinant viruses, Ki-MSV and Ha-MSV. Based on data obtained on the p21 of a mutant of Ki-MSV temperature-sensitive for the maintenance of transformation, we suggest that the gene in RaSV that codes for the p29 is also required for the maintenance of RaSV-induced fibroblast transformation."}
{"id": "PMID:226971", "title": "Thermolabile protein kinase molecules in a temperature-sensitive murine sarcoma virus pseudotype.", "content": "Murine sarcoma virus-associated protein kinases that bind to actin have been purified by affinity chromatography on actin coupled to Sepharose. Heat inactivation studies showed the presence of thermolabile enzyme activity in pseudotypes containing a temperature-sensitivity mutant of murine sarcoma virus (MSV) but not in two independent wild-type MSV pseudotypes. Studies with Sephadex G-75 column fractions showed that a low molecular weight form, approximately 15,000, is the major thermolabile kinase in the temperature-sensitive MSV virions. Antibodies raised against the MSV-coded p60 protein, when added to the in vitro reaction mixtures, showed specific phosphorylation of the IgG heavy chain and a simultaneous reduction in the extent of phosvitin phosphorylation catalyzed by the various MSV pseudotype kinases. Thus a transforming retrovirus-coded enzyme activity that interacts directly with a major cytoskeletal protein and whose activity parallels the transforming ability of a conditional MSV mutant has now been identified.", "contents": "Thermolabile protein kinase molecules in a temperature-sensitive murine sarcoma virus pseudotype. Murine sarcoma virus-associated protein kinases that bind to actin have been purified by affinity chromatography on actin coupled to Sepharose. Heat inactivation studies showed the presence of thermolabile enzyme activity in pseudotypes containing a temperature-sensitivity mutant of murine sarcoma virus (MSV) but not in two independent wild-type MSV pseudotypes. Studies with Sephadex G-75 column fractions showed that a low molecular weight form, approximately 15,000, is the major thermolabile kinase in the temperature-sensitive MSV virions. Antibodies raised against the MSV-coded p60 protein, when added to the in vitro reaction mixtures, showed specific phosphorylation of the IgG heavy chain and a simultaneous reduction in the extent of phosvitin phosphorylation catalyzed by the various MSV pseudotype kinases. Thus a transforming retrovirus-coded enzyme activity that interacts directly with a major cytoskeletal protein and whose activity parallels the transforming ability of a conditional MSV mutant has now been identified."}
{"id": "PMID:226972", "title": "Transcriptional regulation of the yeast cytochrome c gene.", "content": "DNA from the cloned yeast iso-1-cytochrome c, cycl, gene was used in a hybridization assay to measure levels and rates of synthesis of cycl RNA. Derepressed cells synthesized cycl RNA at 6 times the rate of that of glucose-repressed cells. Upon glucose addition to a derepressed culture, the transcription of the cycl gene was repressed within 2.5 min. The half-life of hybridizable cycl RNA was determined to be 12-13.5 min under repressed and derepressed conditions and during repression. The results demonstrate that the expression of the cycl gene is subject to transcriptional regulation.", "contents": "Transcriptional regulation of the yeast cytochrome c gene. DNA from the cloned yeast iso-1-cytochrome c, cycl, gene was used in a hybridization assay to measure levels and rates of synthesis of cycl RNA. Derepressed cells synthesized cycl RNA at 6 times the rate of that of glucose-repressed cells. Upon glucose addition to a derepressed culture, the transcription of the cycl gene was repressed within 2.5 min. The half-life of hybridizable cycl RNA was determined to be 12-13.5 min under repressed and derepressed conditions and during repression. The results demonstrate that the expression of the cycl gene is subject to transcriptional regulation."}
{"id": "PMID:226973", "title": "beta-Endorphin: formation of alpha-helix in lipid solutions.", "content": "Human beta-endorphin adopts a partial helical conformation in aqueous solutions of cerebroside sulfate, ganglioside GM1, phosphatidylserine, and phosphatidic acid, but not of cerebroside and phosphatidylcholine, as evidenced by circular dichroic spectra. Addition of Ca2+ to the peptide in cerebroside sulfate solution can break up the helix; at 10 mM Ca2+ the peptide (12 microM) essentially exists in an unordered form. For comparison, sheep beta-lipotropin in acidic cerebroside sulfate solution (pH less than 4) also has a partial helical conformation of the complex between human beta-endorphin and lipids may be related to the opiatelike function of this peptide hormone.", "contents": "beta-Endorphin: formation of alpha-helix in lipid solutions. Human beta-endorphin adopts a partial helical conformation in aqueous solutions of cerebroside sulfate, ganglioside GM1, phosphatidylserine, and phosphatidic acid, but not of cerebroside and phosphatidylcholine, as evidenced by circular dichroic spectra. Addition of Ca2+ to the peptide in cerebroside sulfate solution can break up the helix; at 10 mM Ca2+ the peptide (12 microM) essentially exists in an unordered form. For comparison, sheep beta-lipotropin in acidic cerebroside sulfate solution (pH less than 4) also has a partial helical conformation of the complex between human beta-endorphin and lipids may be related to the opiatelike function of this peptide hormone."}
{"id": "PMID:226974", "title": "Protein kinase activity associated with the D2 hybrid protein related to simian virus 40 T antigen: some characteristics of the reaction products.", "content": "Protein kinase activity (ATP:protein phosphotransferase, EC 2.7.1.37) has been found associated with the D2 hybrid protein, a highly purified protein of 107,000 daltons specified by the adenovirus-simian virus 40 (SV40) hybrid Ad2(+)D2, which has many properties associated with authentic SV40 T antigen [Tjian, R. & Robbins, A. (1979) Proc. Natl. Acad. Sci. USA 76, 610-614]. We have now examined some of the biochemical characteristics of the reaction products. Acceptors for the terminal phosphoryl group of [gamma-(32)P]ATP are the purified protein itself and at least four proteins extracted from nuclei of uninfected cells. Purified histones do not serve as substrate for the enzyme. Phosphorylation is markedly reduced by heating the D2 hybrid protein to 50 degrees C for 30 min. The products of phosphorylation are stable to treatment with ethanol/ether, DNase, and RNase, but completely degraded by digestion with Pronase, demonstrating their protein nature. The phosphate bonds are liable to hot alkali and sensitive to digestion with alkaline phosphatase but stable to treatment with hot acid or hydroxylamine. These results provide evidence that (32)P is incorporated into O-phosphoserine or O-phosphothreonine residues of acceptor proteins, indicating that the enzymatic activity is characteristic for protein kinase, and that cell-specified nuclear proteins other than histones may serve as substrates for the enzyme.", "contents": "Protein kinase activity associated with the D2 hybrid protein related to simian virus 40 T antigen: some characteristics of the reaction products. Protein kinase activity (ATP:protein phosphotransferase, EC 2.7.1.37) has been found associated with the D2 hybrid protein, a highly purified protein of 107,000 daltons specified by the adenovirus-simian virus 40 (SV40) hybrid Ad2(+)D2, which has many properties associated with authentic SV40 T antigen [Tjian, R. & Robbins, A. (1979) Proc. Natl. Acad. Sci. USA 76, 610-614]. We have now examined some of the biochemical characteristics of the reaction products. Acceptors for the terminal phosphoryl group of [gamma-(32)P]ATP are the purified protein itself and at least four proteins extracted from nuclei of uninfected cells. Purified histones do not serve as substrate for the enzyme. Phosphorylation is markedly reduced by heating the D2 hybrid protein to 50 degrees C for 30 min. The products of phosphorylation are stable to treatment with ethanol/ether, DNase, and RNase, but completely degraded by digestion with Pronase, demonstrating their protein nature. The phosphate bonds are liable to hot alkali and sensitive to digestion with alkaline phosphatase but stable to treatment with hot acid or hydroxylamine. These results provide evidence that (32)P is incorporated into O-phosphoserine or O-phosphothreonine residues of acceptor proteins, indicating that the enzymatic activity is characteristic for protein kinase, and that cell-specified nuclear proteins other than histones may serve as substrates for the enzyme."}
{"id": "PMID:226975", "title": "Interrupting the early region of polyoma virus DNA enhances tumorigenicity.", "content": "The tumorigenicity of DNA from polyoma virus after cleavage with a variety of restriction enzymes was evaluated in suckling hamsters. Cleavage with enzymes that interrupt the region of the genome coding for the large tumor (T) antigen of polyoma virus markedly enhanced the tumorigenicity above that observed with DNA I of the virus. Cell lines established in vitro from tumors induced by polyoma virions, polyoma virus DNA I, or polyoma virus DNA that had been cleaved with restriction endonucleases in the early region all contain the polyoma virus middle and small T antigens but not the large T antigen of polyoma virus is not required for maintenance of the transformed state and probably not for initiation of tumorigenesis by viral DNA.", "contents": "Interrupting the early region of polyoma virus DNA enhances tumorigenicity. The tumorigenicity of DNA from polyoma virus after cleavage with a variety of restriction enzymes was evaluated in suckling hamsters. Cleavage with enzymes that interrupt the region of the genome coding for the large tumor (T) antigen of polyoma virus markedly enhanced the tumorigenicity above that observed with DNA I of the virus. Cell lines established in vitro from tumors induced by polyoma virions, polyoma virus DNA I, or polyoma virus DNA that had been cleaved with restriction endonucleases in the early region all contain the polyoma virus middle and small T antigens but not the large T antigen of polyoma virus is not required for maintenance of the transformed state and probably not for initiation of tumorigenesis by viral DNA."}
{"id": "PMID:226976", "title": "T4 DNA-delay proteins, required for specific DNA replication, form a complex that has ATP-dependent DNA topoisomerase activity.", "content": "Under some conditions, T4 DNA replication requires the products of the DNA-delay genes, genes 39, 52, 58, and 60. By using an in vitro complementation assay that stimulates DNA replication in T4 39(-)-infected cell extracts, T4 gene 39 protein has been purified. The purified fraction also contains complementing activities for T4 genes 52 and 60. On sodium dodecyl sulfate/polyacrylamide gel analysis the purified preparation exhibits three protein components: a 51,000-dalton protein corresponding to the product of gene 52, a 64,000-dalton protein corresponding to the product of gene 39, and a 110,000-dalton protein. This purified fraction shows a DNA topoisomerase activity that untwists superhelical DNA in an ATP- and Mg2+-dependent reaction. The analogs adenylyl imidodiphosphate and adenyl [beta, gamma-methylene]diphosphonate cannot be used to replace ATP. The topoisomerase activity is not sensitive to the antibiotics oxolinic acid and novobiocin, known antagonists of Escherichia coli DNA gyrase. The possible relationship among the three polypeptides and their biological activities is discussed.", "contents": "T4 DNA-delay proteins, required for specific DNA replication, form a complex that has ATP-dependent DNA topoisomerase activity. Under some conditions, T4 DNA replication requires the products of the DNA-delay genes, genes 39, 52, 58, and 60. By using an in vitro complementation assay that stimulates DNA replication in T4 39(-)-infected cell extracts, T4 gene 39 protein has been purified. The purified fraction also contains complementing activities for T4 genes 52 and 60. On sodium dodecyl sulfate/polyacrylamide gel analysis the purified preparation exhibits three protein components: a 51,000-dalton protein corresponding to the product of gene 52, a 64,000-dalton protein corresponding to the product of gene 39, and a 110,000-dalton protein. This purified fraction shows a DNA topoisomerase activity that untwists superhelical DNA in an ATP- and Mg2+-dependent reaction. The analogs adenylyl imidodiphosphate and adenyl [beta, gamma-methylene]diphosphonate cannot be used to replace ATP. The topoisomerase activity is not sensitive to the antibiotics oxolinic acid and novobiocin, known antagonists of Escherichia coli DNA gyrase. The possible relationship among the three polypeptides and their biological activities is discussed."}
{"id": "PMID:226977", "title": "Synthesis of a small RNA in cells coinfected by standard and defective interfering particles of vesicular stomatitis virus.", "content": "A small RNA, containing approximately 50 nucleotides, is synthesized by cells coinfected with standard vesicular stomatitis virus and its defective interfering (DI) particles. Infection of cells by standard virus or DI particles alone does not lead to synthesis of significant amounts of small RNA. The RNA is initiated at its 5' end with (p)ppXp and is not polyadenylylated at the 3' end despite a content of 51% adenosine. It has sequences complementary to the genome of a DI particle. The synthesis of the small RNA correlates with the replication of the genome of DI particles with molar ratio small RNA/genome RNA of DI particles greater than 50. When replication of DI genomes is prevented by the addition of cycloheximide or prior UV irradiation of DI particles, small RNA is not synthesized in coinfected cells. These results indicate that the small RNA is not the result of transcriptional initiation and that it may relate to interference mediated by DI particles.", "contents": "Synthesis of a small RNA in cells coinfected by standard and defective interfering particles of vesicular stomatitis virus. A small RNA, containing approximately 50 nucleotides, is synthesized by cells coinfected with standard vesicular stomatitis virus and its defective interfering (DI) particles. Infection of cells by standard virus or DI particles alone does not lead to synthesis of significant amounts of small RNA. The RNA is initiated at its 5' end with (p)ppXp and is not polyadenylylated at the 3' end despite a content of 51% adenosine. It has sequences complementary to the genome of a DI particle. The synthesis of the small RNA correlates with the replication of the genome of DI particles with molar ratio small RNA/genome RNA of DI particles greater than 50. When replication of DI genomes is prevented by the addition of cycloheximide or prior UV irradiation of DI particles, small RNA is not synthesized in coinfected cells. These results indicate that the small RNA is not the result of transcriptional initiation and that it may relate to interference mediated by DI particles."}
{"id": "PMID:226978", "title": "Cloning of the active thymidine kinase gene of herpes simplex virus type 1 in Escherichia coli K-12.", "content": "A herpes simplex virus DNA fragment that is produced by digestion with BamHI endonuclease and carries the thymidine kinase (TK; ATP:thymidine 5'-phosphotransferase, EC 2.7.1.21) gene has been cloned in Escherichia coli. A recombinat plasmid, pFG5, has been analyzed extensively and a detailed restriction map is presented. pFG5 DNA efficiently transforms TK- mouse L cells. The TK coding sequence in the cloned fragment has been localized and a smaller recombinant plasmid, pAG0, also carrying an active TK gene, has been constructed to serve as a more convenient vector for transfer, into TK- cells, of genes previously cloned in E. coli.", "contents": "Cloning of the active thymidine kinase gene of herpes simplex virus type 1 in Escherichia coli K-12. A herpes simplex virus DNA fragment that is produced by digestion with BamHI endonuclease and carries the thymidine kinase (TK; ATP:thymidine 5'-phosphotransferase, EC 2.7.1.21) gene has been cloned in Escherichia coli. A recombinat plasmid, pFG5, has been analyzed extensively and a detailed restriction map is presented. pFG5 DNA efficiently transforms TK- mouse L cells. The TK coding sequence in the cloned fragment has been localized and a smaller recombinant plasmid, pAG0, also carrying an active TK gene, has been constructed to serve as a more convenient vector for transfer, into TK- cells, of genes previously cloned in E. coli."}
{"id": "PMID:226979", "title": "Nicking-closing activity associated with bacteriophage lambda int gene product.", "content": "Integrative recombination of bacteriophage lambda requires the action of the protein Int, the product of the phage int gene. In this paper we show that highly purified Int relaxes supercoiled DNA. The association of this nicking-closing activity with Int is shown by: (i) the cosedimentation of nicking-closing and recombination activities of purified Int, (ii) the parallel inactivation of the two activities in purified Int by both heat and a specific antiserum, and (iii) the alteration of both activities in crude extracts of a strain expressing a mutant int gene. The nicking-closing activity of Int functions in the absence of divalent cations and in the absence of an apparent source of chemical energy. The activity displays no obvious sequence specificity and is inhibited by Mg2+, spermidine, and single-stranded DNA. Int relaxes positive as well as negative supercoils. We present a model for the mechanism of strand exchange that describes how the nicking-closing activity of Int might be used during recombination.", "contents": "Nicking-closing activity associated with bacteriophage lambda int gene product. Integrative recombination of bacteriophage lambda requires the action of the protein Int, the product of the phage int gene. In this paper we show that highly purified Int relaxes supercoiled DNA. The association of this nicking-closing activity with Int is shown by: (i) the cosedimentation of nicking-closing and recombination activities of purified Int, (ii) the parallel inactivation of the two activities in purified Int by both heat and a specific antiserum, and (iii) the alteration of both activities in crude extracts of a strain expressing a mutant int gene. The nicking-closing activity of Int functions in the absence of divalent cations and in the absence of an apparent source of chemical energy. The activity displays no obvious sequence specificity and is inhibited by Mg2+, spermidine, and single-stranded DNA. Int relaxes positive as well as negative supercoils. We present a model for the mechanism of strand exchange that describes how the nicking-closing activity of Int might be used during recombination."}
{"id": "PMID:226980", "title": "Nicking-closing enzyme assembles nucleosome-like structures in vitro.", "content": "The four core histones (H2A, H2B, H3, and H4) and DNA were assembled into nucleosome-like particles at physiological ionic strengths either by an extract of chromatin rich in nicking-closing activity or by the purified nicking-closing enzyme itself. When histone-DNA complexes were assembled in vitro from relaxed circular DNA, nearly physiological numbers of superhelical turns were induced in the DNA molecule. Electron microscopy of the complexes assembled by the chromatin extract revealed a beaded structure and a reduction of the contour length compared to free DNA. Micrococcal nuclease digestion of the histone-DNA complexes yielded 145-base-pair DNA fragments typical of nucleosome core particles and shorter subnucleosomal DNA fragments of discrete length.", "contents": "Nicking-closing enzyme assembles nucleosome-like structures in vitro. The four core histones (H2A, H2B, H3, and H4) and DNA were assembled into nucleosome-like particles at physiological ionic strengths either by an extract of chromatin rich in nicking-closing activity or by the purified nicking-closing enzyme itself. When histone-DNA complexes were assembled in vitro from relaxed circular DNA, nearly physiological numbers of superhelical turns were induced in the DNA molecule. Electron microscopy of the complexes assembled by the chromatin extract revealed a beaded structure and a reduction of the contour length compared to free DNA. Micrococcal nuclease digestion of the histone-DNA complexes yielded 145-base-pair DNA fragments typical of nucleosome core particles and shorter subnucleosomal DNA fragments of discrete length."}
{"id": "PMID:226981", "title": "Use of the UGA terminator as a tryptophan codon in yeast mitochondria.", "content": "We propose that the UGA terminator regularly occurs as a tryptophan codon in yeast mitochondrial DNA. This conclusion is based on the sequence analysis of mitochondrial DNA regions coding for structural genes of cytochrome b, cytochrome oxidase, and the ATPase.", "contents": "Use of the UGA terminator as a tryptophan codon in yeast mitochondria. We propose that the UGA terminator regularly occurs as a tryptophan codon in yeast mitochondrial DNA. This conclusion is based on the sequence analysis of mitochondrial DNA regions coding for structural genes of cytochrome b, cytochrome oxidase, and the ATPase."}
{"id": "PMID:226982", "title": "Characterization of the iron-sulfur centers in succinate dehydrogenase.", "content": "Two techniques have been applied to the determination of the number and type (2-Fe, 4-Fe) of iron-sulfur centers in the iron-sulfur flavoprotein succinate dehydrogenase [succinate:(acceptor) oxidoreductase, EC 1.3.99.1]. One procedure uses p-CF3C6H4SH as an extrusion reagent and Fourier transform 19F nuclear magentic resonance as the method of detection and quantitation of extruded cores of these centers in the form of [Fe2S2(SRF)4]2- and [Fe4S4(SRF)4]2- (RF = p-C6H4CF3). The second procedure, interprotein core transfer, involves thiol displacement of iron-sulfur cores followed by specific core transfer to the apoproteins of Bacillus polymyxa ferredoxin and adrenodoxin. Detection and quantitation are accomplished by electron paramagnetic resonance of reduced proteins at low temperatures. Both procedures clearly show that succinate dehydrogenase contains two dimeric (Fe2S2) and one tetrameric (Fe4S4) centers per mole of histidyl flavin, accounting for all eight nonheme iron and eight labile sulfur atoms found by chemical analysis. These results remove uncertainties created by the less than stoichiometric amounts of binuclear centers detected by electron paramagnetic resonance after dithionite reduction and provide secure characterization of the iron-sulfur centers in this enzyme.", "contents": "Characterization of the iron-sulfur centers in succinate dehydrogenase. Two techniques have been applied to the determination of the number and type (2-Fe, 4-Fe) of iron-sulfur centers in the iron-sulfur flavoprotein succinate dehydrogenase [succinate:(acceptor) oxidoreductase, EC 1.3.99.1]. One procedure uses p-CF3C6H4SH as an extrusion reagent and Fourier transform 19F nuclear magentic resonance as the method of detection and quantitation of extruded cores of these centers in the form of [Fe2S2(SRF)4]2- and [Fe4S4(SRF)4]2- (RF = p-C6H4CF3). The second procedure, interprotein core transfer, involves thiol displacement of iron-sulfur cores followed by specific core transfer to the apoproteins of Bacillus polymyxa ferredoxin and adrenodoxin. Detection and quantitation are accomplished by electron paramagnetic resonance of reduced proteins at low temperatures. Both procedures clearly show that succinate dehydrogenase contains two dimeric (Fe2S2) and one tetrameric (Fe4S4) centers per mole of histidyl flavin, accounting for all eight nonheme iron and eight labile sulfur atoms found by chemical analysis. These results remove uncertainties created by the less than stoichiometric amounts of binuclear centers detected by electron paramagnetic resonance after dithionite reduction and provide secure characterization of the iron-sulfur centers in this enzyme."}
{"id": "PMID:226983", "title": "Methylation of Herpesvirus saimiri DNA in lymphoid tumor cell lines.", "content": "Several continuous lymphoid cell lines have been established from tumors induced by Herpesvirus saimiri. At least a portion of the viral DNA in the marmoset lymphoid cell line 1670, which does not produce detectable virus, is present as covalently closed circular episomal DNA. The use of restriction endonuclease digestion, transfer to nitrocellulose filters, and hybridization of the virus-specific DNA has produced strong evidence that viral DNA sequences present in total 1670 cell DNA and in isolated episomes are extensively methylated. The restriction endonuclease Hpa II has the same recognition sequence as Msp I but, unlike Msp I, fails to cleave when the C of the C-G dinucleotide is methylated. Viral DNA sequences of 1670 cells are refractory to cleavage by Hpa II but not Msp I; greater than 80% of the Hpa II cleavage sites appear to be methylated. Similarly, viral DNA sequences of 1670 cells are refractory to cleavage by Sma I (C-C-C-G-G-G) and Sac II (C-C-G-C-G-G) but not Sac I, Pvu II, or Pst I, which lack the dinucleotide C-G in their recognition sequences. Methylation of mammalian DNA has been previously found exclusively at C residues in the dinucleotide C-G. H. saimiri DNA sequences of another nonproducer cell line, 70N2, also appeared to be extensively methylated, but analysis of total cell DNA extracted from three virus-producing lymphoid lines revealed no evidence of methylation of viral DNA sequences. It remains to be seen if methylation of viral DNA plays a role in the lack of complete expression of H. saimiri genome information in nonproducing lymphoid cell lines.", "contents": "Methylation of Herpesvirus saimiri DNA in lymphoid tumor cell lines. Several continuous lymphoid cell lines have been established from tumors induced by Herpesvirus saimiri. At least a portion of the viral DNA in the marmoset lymphoid cell line 1670, which does not produce detectable virus, is present as covalently closed circular episomal DNA. The use of restriction endonuclease digestion, transfer to nitrocellulose filters, and hybridization of the virus-specific DNA has produced strong evidence that viral DNA sequences present in total 1670 cell DNA and in isolated episomes are extensively methylated. The restriction endonuclease Hpa II has the same recognition sequence as Msp I but, unlike Msp I, fails to cleave when the C of the C-G dinucleotide is methylated. Viral DNA sequences of 1670 cells are refractory to cleavage by Hpa II but not Msp I; greater than 80% of the Hpa II cleavage sites appear to be methylated. Similarly, viral DNA sequences of 1670 cells are refractory to cleavage by Sma I (C-C-C-G-G-G) and Sac II (C-C-G-C-G-G) but not Sac I, Pvu II, or Pst I, which lack the dinucleotide C-G in their recognition sequences. Methylation of mammalian DNA has been previously found exclusively at C residues in the dinucleotide C-G. H. saimiri DNA sequences of another nonproducer cell line, 70N2, also appeared to be extensively methylated, but analysis of total cell DNA extracted from three virus-producing lymphoid lines revealed no evidence of methylation of viral DNA sequences. It remains to be seen if methylation of viral DNA plays a role in the lack of complete expression of H. saimiri genome information in nonproducing lymphoid cell lines."}
{"id": "PMID:226984", "title": "Protein influence on the heme in cytochrome c: evidence from Raman difference spectroscopy.", "content": "Raman difference spectra have been obtained for the cytochromes c of a number of species by simultaneous data acquisition from two samples. Frequency differences as small as 0.1 cm-1 can be measured reproducibly by the technique we have developed. In comparisons between cytochromes c isolated from two different species, the frequency differences in the heme vibrational modes range from 0 to 6 cm-1. The vibrational frequencies of the heme are sensitive to the electronic charge density on the porphyrin macrocycle. The frequency differences are interpreted in terms of the influence of the heme-packed aromatic and highly electronegative amino acid side chains on the pi* charge density and distribution on the heme. Such a control of the electronic properties of the heme by the protein may be important for the function of cytochrome c.", "contents": "Protein influence on the heme in cytochrome c: evidence from Raman difference spectroscopy. Raman difference spectra have been obtained for the cytochromes c of a number of species by simultaneous data acquisition from two samples. Frequency differences as small as 0.1 cm-1 can be measured reproducibly by the technique we have developed. In comparisons between cytochromes c isolated from two different species, the frequency differences in the heme vibrational modes range from 0 to 6 cm-1. The vibrational frequencies of the heme are sensitive to the electronic charge density on the porphyrin macrocycle. The frequency differences are interpreted in terms of the influence of the heme-packed aromatic and highly electronegative amino acid side chains on the pi* charge density and distribution on the heme. Such a control of the electronic properties of the heme by the protein may be important for the function of cytochrome c."}
{"id": "PMID:226985", "title": "Torsional stress and local denaturation in supercoiled DNA.", "content": "It is shown that local denaturation can be a natural consequence of supercoiling, even in environments where base pairing of linear DNA is energetically favored. Any change in the molecular total twist from its unstressed value is partitioned between local denaturation and smooth twisting in both the native and coil regions so as to minimize the total conformational free energy involved. Threshold degrees of torsional deformation are found for the existence of stable, locally melted conformations. As these thresholds are surpassed, the number of denatured bases increase smoothly from zero. Existing experimental evidence regarding denaturation in supercoiled DNA is in good agreement with the predictions of this theory. In addition, from existing data one can estimate the partitioning of superhelicity between twisting and writhing. Possible consequences of stress-induced strand separation on the accessibility of the DNA to enzyme attack are discussed. Control of local melting by DNA topoisomerases and DNA gyrases could regulate diverse events involved in transcription, replication, recombination, and repair.", "contents": "Torsional stress and local denaturation in supercoiled DNA. It is shown that local denaturation can be a natural consequence of supercoiling, even in environments where base pairing of linear DNA is energetically favored. Any change in the molecular total twist from its unstressed value is partitioned between local denaturation and smooth twisting in both the native and coil regions so as to minimize the total conformational free energy involved. Threshold degrees of torsional deformation are found for the existence of stable, locally melted conformations. As these thresholds are surpassed, the number of denatured bases increase smoothly from zero. Existing experimental evidence regarding denaturation in supercoiled DNA is in good agreement with the predictions of this theory. In addition, from existing data one can estimate the partitioning of superhelicity between twisting and writhing. Possible consequences of stress-induced strand separation on the accessibility of the DNA to enzyme attack are discussed. Control of local melting by DNA topoisomerases and DNA gyrases could regulate diverse events involved in transcription, replication, recombination, and repair."}
{"id": "PMID:226986", "title": "Reactivation of silent rRNA genes by simian virus 40 in human-mouse hybrid cells.", "content": "Mouse-human hybrid cells were used to study the ability of simian virus 40 to regulate the expression of rRNA genes in vivo. In these hybrid cells, only the rRNA genes of the dominant species are expressed; the genes for the rRNA of the recessive species are silent. Simian virus 40 infection of these hybrids led to the production of two distinct 28S rRNA species as analyzed by agarose/2.4% polyacrylamide gel electrophoresis. These species were identified as human and mouse rRNAs. This result was confirmed by histochemical studies which indicated that the nucleolus organizer regions of both mouse and human chromosomes were actively synthesizing rRNA in the virus-infected hybrid cells. These results indicate that simian virus 40 infection can induce the expression of otherwise silent rRNA genes.", "contents": "Reactivation of silent rRNA genes by simian virus 40 in human-mouse hybrid cells. Mouse-human hybrid cells were used to study the ability of simian virus 40 to regulate the expression of rRNA genes in vivo. In these hybrid cells, only the rRNA genes of the dominant species are expressed; the genes for the rRNA of the recessive species are silent. Simian virus 40 infection of these hybrids led to the production of two distinct 28S rRNA species as analyzed by agarose/2.4% polyacrylamide gel electrophoresis. These species were identified as human and mouse rRNAs. This result was confirmed by histochemical studies which indicated that the nucleolus organizer regions of both mouse and human chromosomes were actively synthesizing rRNA in the virus-infected hybrid cells. These results indicate that simian virus 40 infection can induce the expression of otherwise silent rRNA genes."}
{"id": "PMID:226987", "title": "Effect of interferon on concentrations of cyclic nucleotides in cultured cells.", "content": "Constant intracellular concentrations of both adenosine 3',5'-cyclic-monophosphate (cyclic AMP) and guanosine 3',5'-cyclic-monophosphate (cyclic GMP) were obtained when leukemia L1210 cells were cultivated under steady-state conditions in the chemostat. In this sensitive and controlled system addition of mouse interferon resulted in a rapid (5-10 min) increase in the intracellular concentration of cyclic GMP, which preceded by several hours an increase in the intracellular concentration of cyclic AMP. In contrast to the effect of interferon, addition of prostaglandin E1 induced a rapid increase in the intracellular concentration of cyclic AMP without markedly affecting the intracellular concentration of cyclic GMP. It is suggested that the rapid effect of interferon on cyclic GMP plays a role in mediating some of the effects of interferon on cells.", "contents": "Effect of interferon on concentrations of cyclic nucleotides in cultured cells. Constant intracellular concentrations of both adenosine 3',5'-cyclic-monophosphate (cyclic AMP) and guanosine 3',5'-cyclic-monophosphate (cyclic GMP) were obtained when leukemia L1210 cells were cultivated under steady-state conditions in the chemostat. In this sensitive and controlled system addition of mouse interferon resulted in a rapid (5-10 min) increase in the intracellular concentration of cyclic GMP, which preceded by several hours an increase in the intracellular concentration of cyclic AMP. In contrast to the effect of interferon, addition of prostaglandin E1 induced a rapid increase in the intracellular concentration of cyclic AMP without markedly affecting the intracellular concentration of cyclic GMP. It is suggested that the rapid effect of interferon on cyclic GMP plays a role in mediating some of the effects of interferon on cells."}
{"id": "PMID:226988", "title": "Morphological revertants of an avian sarcoma virus-transformed mammalian cell line exhibit tumorigenicity and contain pp60src.", "content": "The biological and biochemical properties of Rous sarcoma virus-transformed and revertant field vole cells were investigated. Revertant vole cells appear morphologically similar to normal, uninfected cells, yet, like transformed vole cells, they are fully capable of growing in agar suspension and producing tumors in athymic nude mice. These highly tumorigenic, yet morphologically normal appearing, vole cells express viral-specific antigens such as the gag gene product (Pr76) but lack the env gene protein (gp85). Moreover, they contain the src gene protein, pp60src. These results support the concept of the pleiotropic nature of the src gene product and in addition suggest that pp60src may have multiply mechanisms of action. With this revertant cell system it may be feasible to distinguish between those biochemical functions of the src gene product that are important for tumorigenicity in vivo and those that are related to in vitro morphological transformation.", "contents": "Morphological revertants of an avian sarcoma virus-transformed mammalian cell line exhibit tumorigenicity and contain pp60src. The biological and biochemical properties of Rous sarcoma virus-transformed and revertant field vole cells were investigated. Revertant vole cells appear morphologically similar to normal, uninfected cells, yet, like transformed vole cells, they are fully capable of growing in agar suspension and producing tumors in athymic nude mice. These highly tumorigenic, yet morphologically normal appearing, vole cells express viral-specific antigens such as the gag gene product (Pr76) but lack the env gene protein (gp85). Moreover, they contain the src gene protein, pp60src. These results support the concept of the pleiotropic nature of the src gene product and in addition suggest that pp60src may have multiply mechanisms of action. With this revertant cell system it may be feasible to distinguish between those biochemical functions of the src gene product that are important for tumorigenicity in vivo and those that are related to in vitro morphological transformation."}
{"id": "PMID:226989", "title": "Proliferation of Rous sarcoma virus-infected, but not of normal, chicken fibroblasts in a medium of reduced calcium and magnesium concentration.", "content": "Both normal and Rous sarcoma virus-infected chicken fibroblasts proliferate actively in a culture medium containing physiological concentrations of calcium (1.2 mM) and magnesium (0.7 mM). In the presence of a physiological concentration of magnesium, reduction of the calcium concentration to 0.125 mM resulted in a significant decrease in the proliferation of the normal, but not of the neoplastic, fibroblasts. Reduction of the magnesium concentration to 0.05 mM in the presence of a physiological concentration of calcium had a similar effect. In a culture medium containing reduced concentrations of both calcium (0.20 mM) and magnesium (0.05 mM), the normal fibroblasts were maintained without proliferation, whereas the Rous sarcoma virus-infected fibroblasts continued to proliferate actively. The cytosol concentrations of ionized calcium and magnesium are known to be regulated by a balance between net passive influx and active extrusion and sequestration. On the basis of this consideration and the findings described above it can be hypothesized that: (i) Fibroblast replication is initiated when cytosolic concentrations of calcium, magnesium, or both rise above a critical level. (ii) Autonomous initiation of replication of neoplastic fibroblasts is a result of failure of cytoplasmic divalent cation homeostasis; alternatively, sarcoma virus infection may endow cells with a divalent cation-independent mechanism that bypasses an initiation mechanism that is, normally, divalent cation-dependent. (iii) Proliferation of normal fibroblasts is controlled by extracellular matrix components that interact with cell surfaces in a manner that limits the permeability of plasma membranes to divalent cations or otherwise functions to lower cytosol divalent cation concentrations.", "contents": "Proliferation of Rous sarcoma virus-infected, but not of normal, chicken fibroblasts in a medium of reduced calcium and magnesium concentration. Both normal and Rous sarcoma virus-infected chicken fibroblasts proliferate actively in a culture medium containing physiological concentrations of calcium (1.2 mM) and magnesium (0.7 mM). In the presence of a physiological concentration of magnesium, reduction of the calcium concentration to 0.125 mM resulted in a significant decrease in the proliferation of the normal, but not of the neoplastic, fibroblasts. Reduction of the magnesium concentration to 0.05 mM in the presence of a physiological concentration of calcium had a similar effect. In a culture medium containing reduced concentrations of both calcium (0.20 mM) and magnesium (0.05 mM), the normal fibroblasts were maintained without proliferation, whereas the Rous sarcoma virus-infected fibroblasts continued to proliferate actively. The cytosol concentrations of ionized calcium and magnesium are known to be regulated by a balance between net passive influx and active extrusion and sequestration. On the basis of this consideration and the findings described above it can be hypothesized that: (i) Fibroblast replication is initiated when cytosolic concentrations of calcium, magnesium, or both rise above a critical level. (ii) Autonomous initiation of replication of neoplastic fibroblasts is a result of failure of cytoplasmic divalent cation homeostasis; alternatively, sarcoma virus infection may endow cells with a divalent cation-independent mechanism that bypasses an initiation mechanism that is, normally, divalent cation-dependent. (iii) Proliferation of normal fibroblasts is controlled by extracellular matrix components that interact with cell surfaces in a manner that limits the permeability of plasma membranes to divalent cations or otherwise functions to lower cytosol divalent cation concentrations."}
{"id": "PMID:226990", "title": "Loss of epidermal growth factor requirement and malignant transformation.", "content": "Serum provides growth factors that regulate and limit the growth of normal cells in tissue culture. Animal cells that are malignantly transformed usually exhibit diminished serum requirements for growth in culture. We have used a defined, serum-free medium to determine which of these growth factors becomes dispensable for the growth of transformed Syrian and Chinese hamster fibroblast cells. The medium's four growth factors-epidermal growth factor (EGF), insulin, fibroblast growth factor, and transferrin-were added or omitted as desired. A decreased requirement for EGF was most closely related to tumorigenicity of chemically (ethyl methanesulfonate) transformed cells in nude mice. All lines examined retained their requirement for transferrin, which is needed throughout the growth cycle, in contrast to the other factors, which are needed primarily in G(1) phase. Lines that had lost their EGF requirement but had retained their insulin requirement were arrested in G(1) by insulin deficiency, indicating that their growth control system remained. Mutagenesis with ethyl methanesulfonate can also create requirements of the transformed cells for unknown factors in serum. We conclude that an initial step that reduces the serum requirement in culture, and in tumorigenesis, is relaxation of the growth-regulatory function of EGF.", "contents": "Loss of epidermal growth factor requirement and malignant transformation. Serum provides growth factors that regulate and limit the growth of normal cells in tissue culture. Animal cells that are malignantly transformed usually exhibit diminished serum requirements for growth in culture. We have used a defined, serum-free medium to determine which of these growth factors becomes dispensable for the growth of transformed Syrian and Chinese hamster fibroblast cells. The medium's four growth factors-epidermal growth factor (EGF), insulin, fibroblast growth factor, and transferrin-were added or omitted as desired. A decreased requirement for EGF was most closely related to tumorigenicity of chemically (ethyl methanesulfonate) transformed cells in nude mice. All lines examined retained their requirement for transferrin, which is needed throughout the growth cycle, in contrast to the other factors, which are needed primarily in G(1) phase. Lines that had lost their EGF requirement but had retained their insulin requirement were arrested in G(1) by insulin deficiency, indicating that their growth control system remained. Mutagenesis with ethyl methanesulfonate can also create requirements of the transformed cells for unknown factors in serum. We conclude that an initial step that reduces the serum requirement in culture, and in tumorigenesis, is relaxation of the growth-regulatory function of EGF."}
{"id": "PMID:226991", "title": "Chinese hamster ovary cell population density affects intracellular concentrations of calcium-dependent regulator and ability of regulator to inhibit adenylate cyclase activity.", "content": "The adenylate cyclase activity [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] of crude Chinese hamster ovary cell membranes was inhibited 30-40% by low concentrations (6-600 ng/ml) of calcium-dependent regulator (CDR). This inhibitory effect was lost at concentrations of CDR above 600 ng/ml. The adenylate cyclase activity of membranes prepared from low population density Chinese hamster ovary cells was not appreciably altered by CDR. However, with increasing cell population density there was a significant increase in the ability of CDR to inhibit cyclic AMP formation. Further, the intracellular levels of CDR determined in the 12,000 x g supernatant and particulate fractions varied inversely with increasing cell population density. As cell number increased from 2 x 10(6) to 10 x 10(6) cells per dish the CDR concentration present in the supernatant fraction increased from 0.4 to 0.8 mug of CDR per mg of protein, while the amount of endogenous CDR associated with the particulate fraction decreased from 0.6 to 0.4 mug of CDR per mg of protein. This suggests that possible changes in the distribution of CDR between the supernatant and membrane fractions might serve as a regulatory mechanism for activities under CDR control.", "contents": "Chinese hamster ovary cell population density affects intracellular concentrations of calcium-dependent regulator and ability of regulator to inhibit adenylate cyclase activity. The adenylate cyclase activity [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] of crude Chinese hamster ovary cell membranes was inhibited 30-40% by low concentrations (6-600 ng/ml) of calcium-dependent regulator (CDR). This inhibitory effect was lost at concentrations of CDR above 600 ng/ml. The adenylate cyclase activity of membranes prepared from low population density Chinese hamster ovary cells was not appreciably altered by CDR. However, with increasing cell population density there was a significant increase in the ability of CDR to inhibit cyclic AMP formation. Further, the intracellular levels of CDR determined in the 12,000 x g supernatant and particulate fractions varied inversely with increasing cell population density. As cell number increased from 2 x 10(6) to 10 x 10(6) cells per dish the CDR concentration present in the supernatant fraction increased from 0.4 to 0.8 mug of CDR per mg of protein, while the amount of endogenous CDR associated with the particulate fraction decreased from 0.6 to 0.4 mug of CDR per mg of protein. This suggests that possible changes in the distribution of CDR between the supernatant and membrane fractions might serve as a regulatory mechanism for activities under CDR control."}
{"id": "PMID:226992", "title": "Stereospecific hexose transport by membrane vesicles from mouse fibroblasts: membrane vesicles retain increased hexose transport associated with viral transformation.", "content": "Membrane vesicles isolated from nontransformed BALB/c 3T3 mouse fibroblasts (3T3) and from those cells transformed by simian virus 40 (SV3T3) displayed carrier-mediated and stereospecific uptake of hexose as measured by the difference between D-[(14)C]glucose or its analogues and L-[(3)H]glucose uptake. Stereospecific uptake appeared to be linear for 5 sec and reached a maximum at 5-10 min. Stereospecific D-[(14)C]glucose uptake, osmotically sensitive and temperature dependent, was inhibited by unlabeled D-glucose or its analogues and was stimulated by the countertransport of accumulated unlabeled D-glucose. As with whole cells, the initial rate of stereospecific uptake by SV3T3 membrane vesicles was approximately 2.5-fold greater than that by 3T3 vesicles. Efflux of preloaded D-[(14)C]glucose was also faster from SV3T3 than from 3T3 membrane vesicles. The K(m) value was 5 mM for both the 3T3 and the SV3T3 membrane vesicles, but the V(max) values were 36 and 86 nmol/mg of protein per min, respectively, suggesting an increase in the number or availability of hexose carriers in transformed cell membranes. Cytochalasin B competitively inhibited stereospecific hexose uptake in both types of membrane vesicles. The binding of cytochalasin B to the SV3T3 membrane vesicles was significantly greater than that to 3T3 vesicles. Thus, the membrane vesicles retained many of the features of the altered hexose transport observed in whole cells in association with viral transformation.", "contents": "Stereospecific hexose transport by membrane vesicles from mouse fibroblasts: membrane vesicles retain increased hexose transport associated with viral transformation. Membrane vesicles isolated from nontransformed BALB/c 3T3 mouse fibroblasts (3T3) and from those cells transformed by simian virus 40 (SV3T3) displayed carrier-mediated and stereospecific uptake of hexose as measured by the difference between D-[(14)C]glucose or its analogues and L-[(3)H]glucose uptake. Stereospecific uptake appeared to be linear for 5 sec and reached a maximum at 5-10 min. Stereospecific D-[(14)C]glucose uptake, osmotically sensitive and temperature dependent, was inhibited by unlabeled D-glucose or its analogues and was stimulated by the countertransport of accumulated unlabeled D-glucose. As with whole cells, the initial rate of stereospecific uptake by SV3T3 membrane vesicles was approximately 2.5-fold greater than that by 3T3 vesicles. Efflux of preloaded D-[(14)C]glucose was also faster from SV3T3 than from 3T3 membrane vesicles. The K(m) value was 5 mM for both the 3T3 and the SV3T3 membrane vesicles, but the V(max) values were 36 and 86 nmol/mg of protein per min, respectively, suggesting an increase in the number or availability of hexose carriers in transformed cell membranes. Cytochalasin B competitively inhibited stereospecific hexose uptake in both types of membrane vesicles. The binding of cytochalasin B to the SV3T3 membrane vesicles was significantly greater than that to 3T3 vesicles. Thus, the membrane vesicles retained many of the features of the altered hexose transport observed in whole cells in association with viral transformation."}
{"id": "PMID:226993", "title": "Molecular analysis of chromosome-mediated gene transfer.", "content": "Metaphase chromosomes isolated from a cell line carrying the thymidine kinase (TK) gene of herpes simplex virus type I were used to transform the TK-deficient cell line LMTK- to the TK+ phenotype. Four independent transformants were isolated, all of which expressed virus-specific TK. Each of the four transformant cell lines initially became TK- at a rate of 12% per day. All four transformants possessed multiple copies of the TK gene and in one of the four a rearrangement occurred adjacent to the TK sequences. Stable TK+ derivatives of each line, isolated after prolonged cultivation, retained fewer copies of the TK gene than did their unstable parents. The transferred chromosomal fragment was larger than 17 kilobases in each line.", "contents": "Molecular analysis of chromosome-mediated gene transfer. Metaphase chromosomes isolated from a cell line carrying the thymidine kinase (TK) gene of herpes simplex virus type I were used to transform the TK-deficient cell line LMTK- to the TK+ phenotype. Four independent transformants were isolated, all of which expressed virus-specific TK. Each of the four transformant cell lines initially became TK- at a rate of 12% per day. All four transformants possessed multiple copies of the TK gene and in one of the four a rearrangement occurred adjacent to the TK sequences. Stable TK+ derivatives of each line, isolated after prolonged cultivation, retained fewer copies of the TK gene than did their unstable parents. The transferred chromosomal fragment was larger than 17 kilobases in each line."}
{"id": "PMID:226994", "title": "Amyloid protein SAA is an apoprotein of mouse plasma high density lipoprotein.", "content": "Mouse plasma contains a protein antigenically related to mouse protein AA, the principal protein derived from tissue deposits of amyloid substance in mice. In this work the plasma antigen, SAA, was found mainly as a high molecular weight form (2 x 10(5)) residing for the most part in the density interval 1.063-1.21 g/cm3 (high density lipoprotein, HDL); the largest amount of SAA, absolute and relative to total protein, was found in the density interval 1.125-12.1 g/cm3 (HDL3). When apoproteins of the mouse HDL obtained by delipidation of the lipoprotein particles were chromatographed in acid/urea, the antigenic activity appeared in the 10,000- to 15,000-dalton portion of the apoprotein complex. In these characteristics mouse SAA closely resembles human SAA and the behavior of the protein related to amyloid protein AA indicates that is one of the apoproteins of the HDL complex in both species. Therefore we suggest that it be named apoSAA.", "contents": "Amyloid protein SAA is an apoprotein of mouse plasma high density lipoprotein. Mouse plasma contains a protein antigenically related to mouse protein AA, the principal protein derived from tissue deposits of amyloid substance in mice. In this work the plasma antigen, SAA, was found mainly as a high molecular weight form (2 x 10(5)) residing for the most part in the density interval 1.063-1.21 g/cm3 (high density lipoprotein, HDL); the largest amount of SAA, absolute and relative to total protein, was found in the density interval 1.125-12.1 g/cm3 (HDL3). When apoproteins of the mouse HDL obtained by delipidation of the lipoprotein particles were chromatographed in acid/urea, the antigenic activity appeared in the 10,000- to 15,000-dalton portion of the apoprotein complex. In these characteristics mouse SAA closely resembles human SAA and the behavior of the protein related to amyloid protein AA indicates that is one of the apoproteins of the HDL complex in both species. Therefore we suggest that it be named apoSAA."}
{"id": "PMID:226995", "title": "In vitro infectivity assay for mouse mammary tumor virus.", "content": "Studies of mouse mammary tumor virus (MMTV) have been impeded by the lack of an in vitro infectivity assay. We have developed a rapid, quantitative in vitro assay for MMTV infectivity based on the detection of positively staining foci by immunoperoxidase. This assay and a 50% end-point titration of MMTV infectivity gave identical virus titers. Infection of a rat hepatoma cell line, a feline kidney cell line, and a normal murine mammary gland cell line by virus from the mouse mammary tumor GR3A cell line was linear with respect to virus concentration. The infectious titers obtained in both homologous and heterologous cell lines were not significantly different, demonstrating a lack of host range specificity. Virus infectivity was inactivated by heating at 55 degrees C and by ultraviolet irradiation. Rabbit anti-MMTV serum neutralized the infectivity with a 50% neutralization end point of 1:5000. Applications of this assay to the study of the immunological, biological, and biochemical characteristics of MMTV are discussed.", "contents": "In vitro infectivity assay for mouse mammary tumor virus. Studies of mouse mammary tumor virus (MMTV) have been impeded by the lack of an in vitro infectivity assay. We have developed a rapid, quantitative in vitro assay for MMTV infectivity based on the detection of positively staining foci by immunoperoxidase. This assay and a 50% end-point titration of MMTV infectivity gave identical virus titers. Infection of a rat hepatoma cell line, a feline kidney cell line, and a normal murine mammary gland cell line by virus from the mouse mammary tumor GR3A cell line was linear with respect to virus concentration. The infectious titers obtained in both homologous and heterologous cell lines were not significantly different, demonstrating a lack of host range specificity. Virus infectivity was inactivated by heating at 55 degrees C and by ultraviolet irradiation. Rabbit anti-MMTV serum neutralized the infectivity with a 50% neutralization end point of 1:5000. Applications of this assay to the study of the immunological, biological, and biochemical characteristics of MMTV are discussed."}
{"id": "PMID:226996", "title": "Biogenesis of poxviruses: role for the DNA-dependent RNA polymerase II of the host during expression of late functions.", "content": "The participation of host RNA polymerase II in the vaccinia life cycle was examined by comparing efficiency of multiplication after treating the Ama+ sensitive and Ama 102 drug resistant lines with alpha-amanitin. In the latter, resistance is due to a mutation in RNA polymerase II. The toxin profoundly reduces synthesis of virus-specified polypeptides and morphopoeisis in Ama+ but not in Ama 102 rat myoblasts without appreciably altering vaccinia DNA replication in either cell type. This implicates RNA polymerase II in the expression of late virus functions. Circumstantial evidence from a model system indicates that gamma irradiation of the host prior to infection might disrupt transcription into functional mRNA from the nucleus. Irradiation does not, however, alter the capability of the host to support vaccinia multiplication fully. Therefore, ongoing host nuclear transcription may not be required by this virus. The above results are consistent with the ability of cytoplasts to produce small quantities of mature progeny. Our studies lead us to hypothesize that RNA polymerase II or a subunit of the host enzyme may participate directly in late transcription of the vaccinia genome.", "contents": "Biogenesis of poxviruses: role for the DNA-dependent RNA polymerase II of the host during expression of late functions. The participation of host RNA polymerase II in the vaccinia life cycle was examined by comparing efficiency of multiplication after treating the Ama+ sensitive and Ama 102 drug resistant lines with alpha-amanitin. In the latter, resistance is due to a mutation in RNA polymerase II. The toxin profoundly reduces synthesis of virus-specified polypeptides and morphopoeisis in Ama+ but not in Ama 102 rat myoblasts without appreciably altering vaccinia DNA replication in either cell type. This implicates RNA polymerase II in the expression of late virus functions. Circumstantial evidence from a model system indicates that gamma irradiation of the host prior to infection might disrupt transcription into functional mRNA from the nucleus. Irradiation does not, however, alter the capability of the host to support vaccinia multiplication fully. Therefore, ongoing host nuclear transcription may not be required by this virus. The above results are consistent with the ability of cytoplasts to produce small quantities of mature progeny. Our studies lead us to hypothesize that RNA polymerase II or a subunit of the host enzyme may participate directly in late transcription of the vaccinia genome."}
{"id": "PMID:226997", "title": "Cholinergic activity regulates muscarinic receptors in central nervous system cultures.", "content": "Muscarinic acetylcholine receptor activation induces a loss of muscarinic receptors from cultured neuroblastoma and embryonic chicken cerebrum cells. As measured by specific binding of [3H]quinuclidinyl benzilate, steady-state receptor concentrations decrease 75% in response to receptor-saturating concentrations of cholinomimetic drugs. Both the degree and duration of activation determine the extent of receptor loss. A method for analyzing receptor turnover, which does not rely upon protein synthesis inhibitors, shows that activated receptors have a half-life of 1.6 hr. The regulated rate of receptor disappearance begins as soon as activators are added, and the rate is maintained as long as activators are present. The receptor blocker atropine causes an increase in receptor levels in central nervous system cultures but has no effect on receptors in cultures of adrenergic neuroblastoma cells. Because spontaneous cholinergic activity is expected only in the central nervous system cultures, the increase likely reflects blockade of endogenous regulation. Cytochalasin B blocks receptor regulation, suggesting that regulation may be mediated by a process involving microfilaments.", "contents": "Cholinergic activity regulates muscarinic receptors in central nervous system cultures. Muscarinic acetylcholine receptor activation induces a loss of muscarinic receptors from cultured neuroblastoma and embryonic chicken cerebrum cells. As measured by specific binding of [3H]quinuclidinyl benzilate, steady-state receptor concentrations decrease 75% in response to receptor-saturating concentrations of cholinomimetic drugs. Both the degree and duration of activation determine the extent of receptor loss. A method for analyzing receptor turnover, which does not rely upon protein synthesis inhibitors, shows that activated receptors have a half-life of 1.6 hr. The regulated rate of receptor disappearance begins as soon as activators are added, and the rate is maintained as long as activators are present. The receptor blocker atropine causes an increase in receptor levels in central nervous system cultures but has no effect on receptors in cultures of adrenergic neuroblastoma cells. Because spontaneous cholinergic activity is expected only in the central nervous system cultures, the increase likely reflects blockade of endogenous regulation. Cytochalasin B blocks receptor regulation, suggesting that regulation may be mediated by a process involving microfilaments."}
{"id": "PMID:226998", "title": "Toad urinary bladder epithelial cells in culture: maintenance of epithelial structure, sodium transport, and response to hormones.", "content": "Epithelial cells from the toad urinary bladder have been grown in continuous culture. Many of the cells resemble the granular cell type of the urinary bladder. They form an epithelium with typical tight junctions and gap junctions. The transport properties of two cell lines have been examined. When cells of the line designated TB-M or of line TB-6c are grown on collagen-coated nucleopore filters, epithelia are formed that have transepithelial potential differences of 40 and 20 mV, resistances of 5000 and 10,000 omega-cm2, and short-circuit currents (ISC) of 8.5 and 2.5 muA/cm2, respectively. Net mucosa to serosa sodium transport accounts for all of ISC in line TB-M and for 70% of ISC in line TB-6c. Vasopressin, which stimulates adenylate cylase and ISC in the intact bladder, has no effect on the cells in culture. Cyclic AMP stimulates ISC and lowers resistance in both lines. Aldosterone stimulates ISC in both lines. This is accompanied by a fall in resistance in line TB-M and no change in resistance in line TB-6c. Amiloride inhibits ISC in TB-M cells under basal conditions and after stimulation by aldosterone. In line TB-6c amiloride has no effect under basal conditions but lowers ISC of aldosterone-treated cells to the basal level. Thus, the cells have retained the ability to form oriented, high-resistance epithelial membranes that manifest hormone-sensitive transepithelial sodium transport.", "contents": "Toad urinary bladder epithelial cells in culture: maintenance of epithelial structure, sodium transport, and response to hormones. Epithelial cells from the toad urinary bladder have been grown in continuous culture. Many of the cells resemble the granular cell type of the urinary bladder. They form an epithelium with typical tight junctions and gap junctions. The transport properties of two cell lines have been examined. When cells of the line designated TB-M or of line TB-6c are grown on collagen-coated nucleopore filters, epithelia are formed that have transepithelial potential differences of 40 and 20 mV, resistances of 5000 and 10,000 omega-cm2, and short-circuit currents (ISC) of 8.5 and 2.5 muA/cm2, respectively. Net mucosa to serosa sodium transport accounts for all of ISC in line TB-M and for 70% of ISC in line TB-6c. Vasopressin, which stimulates adenylate cylase and ISC in the intact bladder, has no effect on the cells in culture. Cyclic AMP stimulates ISC and lowers resistance in both lines. Aldosterone stimulates ISC in both lines. This is accompanied by a fall in resistance in line TB-M and no change in resistance in line TB-6c. Amiloride inhibits ISC in TB-M cells under basal conditions and after stimulation by aldosterone. In line TB-6c amiloride has no effect under basal conditions but lowers ISC of aldosterone-treated cells to the basal level. Thus, the cells have retained the ability to form oriented, high-resistance epithelial membranes that manifest hormone-sensitive transepithelial sodium transport."}
{"id": "PMID:226999", "title": "Alteration of cyclic nucleotide levels in brain following intracranial self-stimulation in the rat.", "content": "In a first experiment, 14 rats were implanted with an electrode in the ventral tegmental area and trained to self-stimulate. On the experimental day only half of the rats were allowed to self-stimulate for about one hour. All rats were then sacrificed by immersion in liquid nitrogen. Seven brain regions were dissected and assayed for the endogenous concentration of cyclic nucleotides. Self-stimulation induced significant changes in striatum and hippocampus. However, a subsequent experiment showed that the same pattern of changes in the striatum can be produced by motor activity. On the other hand, changes in the hippocampus were specific to the self-stimulation group suggesting that this structure is associated with the brain reward system.", "contents": "Alteration of cyclic nucleotide levels in brain following intracranial self-stimulation in the rat. In a first experiment, 14 rats were implanted with an electrode in the ventral tegmental area and trained to self-stimulate. On the experimental day only half of the rats were allowed to self-stimulate for about one hour. All rats were then sacrificed by immersion in liquid nitrogen. Seven brain regions were dissected and assayed for the endogenous concentration of cyclic nucleotides. Self-stimulation induced significant changes in striatum and hippocampus. However, a subsequent experiment showed that the same pattern of changes in the striatum can be produced by motor activity. On the other hand, changes in the hippocampus were specific to the self-stimulation group suggesting that this structure is associated with the brain reward system."}
{"id": "PMID:227008", "title": "Effect of adrenaline and triamcinolone on cytochrome oxidase activity in the brain and liver of young and adult rats.", "content": "The effect of adrenaline (0.15 i.p./kg b.w.) and of the synthetic glucocorticoid triamcinolone (40 mg i.p./kg b.w.) on cytochrome oxidase activity, the terminal enzyme of the cytochrome system, was studied in homogenates of the cerebral cortex, subcortical formations (including the basal ganglia, the thalamus and the hypothalamus), the medulla oblongata and the liver of 5-day-old and adult rats. Activity in the above mentioned homogenates was measured polarographically 15 and 30 min after administering adrenaline or 48 h after administering triamcinolone. Fifteen minutes after its injection, adrenaline caused a statistically significant drop in cytochrome oxidase activity in the cerebral cortex, subcortical formations and liver of 5-day-old rats. The decrease still persisted 30 min after administration of the hormone, but was intensified only in the liver. In adult rats, on the other hand, a significant increase in activity was observed in the cerebral cortex and liver after adrenaline. Triamcinolone had no effect on cytochrome oxidase activity in any of the given parts of the brain in either young or adult rats. It significantly stimulated cytochrome oxidase activity in the liver of 5-day-old rats, but severely inhibited it in the liver of adult rats.", "contents": "Effect of adrenaline and triamcinolone on cytochrome oxidase activity in the brain and liver of young and adult rats. The effect of adrenaline (0.15 i.p./kg b.w.) and of the synthetic glucocorticoid triamcinolone (40 mg i.p./kg b.w.) on cytochrome oxidase activity, the terminal enzyme of the cytochrome system, was studied in homogenates of the cerebral cortex, subcortical formations (including the basal ganglia, the thalamus and the hypothalamus), the medulla oblongata and the liver of 5-day-old and adult rats. Activity in the above mentioned homogenates was measured polarographically 15 and 30 min after administering adrenaline or 48 h after administering triamcinolone. Fifteen minutes after its injection, adrenaline caused a statistically significant drop in cytochrome oxidase activity in the cerebral cortex, subcortical formations and liver of 5-day-old rats. The decrease still persisted 30 min after administration of the hormone, but was intensified only in the liver. In adult rats, on the other hand, a significant increase in activity was observed in the cerebral cortex and liver after adrenaline. Triamcinolone had no effect on cytochrome oxidase activity in any of the given parts of the brain in either young or adult rats. It significantly stimulated cytochrome oxidase activity in the liver of 5-day-old rats, but severely inhibited it in the liver of adult rats."}
{"id": "PMID:227010", "title": "Emergency hepatic arterial embolization for secondary hypercalcemia in hepatocellular carcinoma.", "content": "Two successive hepatic arterial embolizations were performed in a patient with hypercalcemia secondary to hepatocellular carcinoma. The first procedure was performed on an emergency basis due to a cardiovascular episode and was immediately beneficial. The second procedure, performed five months later for a recurrence, was effective in 3 days; 13 months later, there had been no recurrence.", "contents": "Emergency hepatic arterial embolization for secondary hypercalcemia in hepatocellular carcinoma. Two successive hepatic arterial embolizations were performed in a patient with hypercalcemia secondary to hepatocellular carcinoma. The first procedure was performed on an emergency basis due to a cardiovascular episode and was immediately beneficial. The second procedure, performed five months later for a recurrence, was effective in 3 days; 13 months later, there had been no recurrence."}
{"id": "PMID:227011", "title": "Preoperative diagnosis and localization of aldosteronomas by measurement of corticosteroids in adrenal venous blood.", "content": "Adrenal venous aldosterone/cortisol ratios were determined in 14 patients with primary aldosteronism. Of 12 patients diagnosed as having an adrenal adenoma, ten underwent surgery in which an adenoma was found. Bilateral adrenal hyperplasia was thought to have developed in two other patients. Measurement of adrenal vein cortisol and establishment of aldosterone/cortisol ratios were done to correct for catheter placement and dilute adrenal efflux. Determination of steroids after ACTH stimulation was helpful in distinguishing quiescent from suppressed adrenal in two patients and in confirming the diagnosis of the others.", "contents": "Preoperative diagnosis and localization of aldosteronomas by measurement of corticosteroids in adrenal venous blood. Adrenal venous aldosterone/cortisol ratios were determined in 14 patients with primary aldosteronism. Of 12 patients diagnosed as having an adrenal adenoma, ten underwent surgery in which an adenoma was found. Bilateral adrenal hyperplasia was thought to have developed in two other patients. Measurement of adrenal vein cortisol and establishment of aldosterone/cortisol ratios were done to correct for catheter placement and dilute adrenal efflux. Determination of steroids after ACTH stimulation was helpful in distinguishing quiescent from suppressed adrenal in two patients and in confirming the diagnosis of the others."}
{"id": "PMID:227012", "title": "The computed tomographic appearance of the normal pituitary gland and pituitary microadenomas.", "content": "With the use of axial and coronal computed tomography (CT), the authors compared the density, contrast enhancement, and dimensions of normal pituitary glands and pituitary microadenomas. The normal gland appears homogeneous, nearly isodense with brain tissue, and it enhances uniformly. Its upper surface is concave downward or flat and its height 2-7 mm. The cavernous sinuses, the third, fourth, and sixth cranial nerves, the infundibulum, and the adjacent carotid arteries are well demonstrated by CT. Abnormal height and upward convexity of the gland are reliable signs of prolactinoma; abnormal density and enhancement are suggestive signs. CT findings in prolactin- and ACTH-secreting tumors may differ. CT is more sensitive and more specific than polytomography in the diagnosis of pituitary adenoma.", "contents": "The computed tomographic appearance of the normal pituitary gland and pituitary microadenomas. With the use of axial and coronal computed tomography (CT), the authors compared the density, contrast enhancement, and dimensions of normal pituitary glands and pituitary microadenomas. The normal gland appears homogeneous, nearly isodense with brain tissue, and it enhances uniformly. Its upper surface is concave downward or flat and its height 2-7 mm. The cavernous sinuses, the third, fourth, and sixth cranial nerves, the infundibulum, and the adjacent carotid arteries are well demonstrated by CT. Abnormal height and upward convexity of the gland are reliable signs of prolactinoma; abnormal density and enhancement are suggestive signs. CT findings in prolactin- and ACTH-secreting tumors may differ. CT is more sensitive and more specific than polytomography in the diagnosis of pituitary adenoma."}
{"id": "PMID:227013", "title": "Early imaging of experimental intestinal infarction with 99mTc-pyrophosphate.", "content": "Extensive mucosal small-bowel infarction was produced in 8 dogs by occluding the cranial mesenteric artery. After one hour of reperfusion, 15 mCi (555 MBq) of 99mTc-pyrophosphate was intra-arterially injected into 4 dogs and venously into the other 4. Positive images were obtained in all dogs except 1 which had received an intravenous injection. Diagnostic images were obtained consistently as early as 15 minutes after injection, and the infarcted bowel could still be visualized two hours later. The average tracer content in infarcted small bowel was 0.015% I.D./g. This was about eight times the uptake found in normal dogs. The results show that experimental small-bowel infarction can be detected as early as five hours after the onset of ischemia.", "contents": "Early imaging of experimental intestinal infarction with 99mTc-pyrophosphate. Extensive mucosal small-bowel infarction was produced in 8 dogs by occluding the cranial mesenteric artery. After one hour of reperfusion, 15 mCi (555 MBq) of 99mTc-pyrophosphate was intra-arterially injected into 4 dogs and venously into the other 4. Positive images were obtained in all dogs except 1 which had received an intravenous injection. Diagnostic images were obtained consistently as early as 15 minutes after injection, and the infarcted bowel could still be visualized two hours later. The average tracer content in infarcted small bowel was 0.015% I.D./g. This was about eight times the uptake found in normal dogs. The results show that experimental small-bowel infarction can be detected as early as five hours after the onset of ischemia."}
{"id": "PMID:227016", "title": "Evidence for the existence of alpha-adrenoceptors in the rat lung.", "content": "Isolated rat lung parenchymal strips responded to carbachol, 5-HT and phenylephrine (PE) with contractions. Bradykinin (BK), histamine, PGF2 alpha, PGE1, PGE2 and dimaprit were either inactive or produced weak relaxations. Isoproterenol, noradrenaline (NA) and epinephrine (E) relaxed lung strips. The further increase in their concentrations produced contractions of varying magnitudes. The lung strips contracted to 5-HT or carbachol, responded to isoproterenol and E and NA with relaxations. Metiamide and cimetidine (selective histamine H2-receptor antagonists) did not alter responses to histamine and carbachol. Propranolol (a beta-adrenoceptor blocker) antagnoized or reversed relaxations to E and isoproterenol, and markedly enhanced contractions to NA, PE and E. Atropine and phentolamine or dibenzyline antagonized contractions to carbachol and sympathomimetic agents, respectively. From study it may be concluded that there are alpha- and beta-adrenergic receptors mediating contractions and relaxations in the peripheral airways of rat.", "contents": "Evidence for the existence of alpha-adrenoceptors in the rat lung. Isolated rat lung parenchymal strips responded to carbachol, 5-HT and phenylephrine (PE) with contractions. Bradykinin (BK), histamine, PGF2 alpha, PGE1, PGE2 and dimaprit were either inactive or produced weak relaxations. Isoproterenol, noradrenaline (NA) and epinephrine (E) relaxed lung strips. The further increase in their concentrations produced contractions of varying magnitudes. The lung strips contracted to 5-HT or carbachol, responded to isoproterenol and E and NA with relaxations. Metiamide and cimetidine (selective histamine H2-receptor antagonists) did not alter responses to histamine and carbachol. Propranolol (a beta-adrenoceptor blocker) antagnoized or reversed relaxations to E and isoproterenol, and markedly enhanced contractions to NA, PE and E. Atropine and phentolamine or dibenzyline antagonized contractions to carbachol and sympathomimetic agents, respectively. From study it may be concluded that there are alpha- and beta-adrenergic receptors mediating contractions and relaxations in the peripheral airways of rat."}
{"id": "PMID:227017", "title": "Effect of paraquat treatment on prolyl hydroxylase activity and collagen synthesis of rat lung and kidney.", "content": "Morphological evidence has shown that the herbicide paraquat produces severe lung fibrosis in experimental animals. In order to investigate the biochemical basis for this fibrosis, prolyl hydroxylase activity, total hydroxyproline content and collagen and protein synthesis were estimated in rats (200 gm) which were pretreated with paraquat (25 mg/Kg; I.P.) nine days before sacrifice. Prolyl hydroxylase activity in the treated rats was significantly elevated in the lungs. However, no such increase was seen in the kidney. There was no significant change in the total hydroxyproline content or collagen formation in the treated animals. When paraquat was added to the culture medium and incubated with lung slices, there was a marked decrease in collagen synthesis along with a decrease in protein synthesis. When paraquat was added to lung cells in culture, it was found that lung explants were more sensitive to paraquat toxicity than cells obtained by trypsinization. In explants which were sensitive to paraquat, there was a marked decrease in both protein synthesis and collagen synthesis.", "contents": "Effect of paraquat treatment on prolyl hydroxylase activity and collagen synthesis of rat lung and kidney. Morphological evidence has shown that the herbicide paraquat produces severe lung fibrosis in experimental animals. In order to investigate the biochemical basis for this fibrosis, prolyl hydroxylase activity, total hydroxyproline content and collagen and protein synthesis were estimated in rats (200 gm) which were pretreated with paraquat (25 mg/Kg; I.P.) nine days before sacrifice. Prolyl hydroxylase activity in the treated rats was significantly elevated in the lungs. However, no such increase was seen in the kidney. There was no significant change in the total hydroxyproline content or collagen formation in the treated animals. When paraquat was added to the culture medium and incubated with lung slices, there was a marked decrease in collagen synthesis along with a decrease in protein synthesis. When paraquat was added to lung cells in culture, it was found that lung explants were more sensitive to paraquat toxicity than cells obtained by trypsinization. In explants which were sensitive to paraquat, there was a marked decrease in both protein synthesis and collagen synthesis."}
{"id": "PMID:227018", "title": "Modification of a commercial microwave oven for animal sacrifice in cyclic GMP assays.", "content": "After sacrifice with a modified Litton Minutemaster(R) commercial oven rat cerebellar tissues were assayed for cyclic guanosine 3',5'-monophosphate (cGMP) concentrations. The results were found to be comparable to recent literature reports in which microwave sacrifice employed considerably more intense and more costly energy sources.", "contents": "Modification of a commercial microwave oven for animal sacrifice in cyclic GMP assays. After sacrifice with a modified Litton Minutemaster(R) commercial oven rat cerebellar tissues were assayed for cyclic guanosine 3',5'-monophosphate (cGMP) concentrations. The results were found to be comparable to recent literature reports in which microwave sacrifice employed considerably more intense and more costly energy sources."}
{"id": "PMID:227015", "title": "[Fatal varicella pneumonia in adults. Report of two cases and review of literature (author's transl)].", "content": "Two mortal cases of varicella pneumonitis are described. The patients were respectively 41 and 34 years-old men of good health. They caught the disease from their children. The disease lasted one week, and death was due in both cases to respiratory failure. The autopsy confirmed massive lung involvement with varicella pneumonia, and also showed other organs involvement (liver, spleen, pancreas, lymph nodes, oesophagus). In both cases, human fibroblast cultures infected by material obtained from cutaneous lesions (in the second case also from the spleen) revealed the presence of Herpesvirus varicellae. A review of 41 cases of adult mortal varicella in the literature demonstrates that death is practically always due to pneumonia and consequent respiratory failure. The dissemination of the virus in other organs is constant. Circumstances, such as pregnancy, immunosuppression, etc., which aggravate the prognosis of varicella in adults, are discussed.", "contents": "[Fatal varicella pneumonia in adults. Report of two cases and review of literature (author's transl)]. Two mortal cases of varicella pneumonitis are described. The patients were respectively 41 and 34 years-old men of good health. They caught the disease from their children. The disease lasted one week, and death was due in both cases to respiratory failure. The autopsy confirmed massive lung involvement with varicella pneumonia, and also showed other organs involvement (liver, spleen, pancreas, lymph nodes, oesophagus). In both cases, human fibroblast cultures infected by material obtained from cutaneous lesions (in the second case also from the spleen) revealed the presence of Herpesvirus varicellae. A review of 41 cases of adult mortal varicella in the literature demonstrates that death is practically always due to pneumonia and consequent respiratory failure. The dissemination of the virus in other organs is constant. Circumstances, such as pregnancy, immunosuppression, etc., which aggravate the prognosis of varicella in adults, are discussed."}
{"id": "PMID:227021", "title": "Respiratory and hemodynamic study during wakefulness and sleep in myotonic dystrophy.", "content": "Six young male patients with grade I (mild) myotonic dystrophy and a complaint of excessive daytime sleepiness were studied during wakefulness and sleep. Pulmonary function tests during wakefulness showed evidence of mild abnormality related to respiratory muscle weakness. During sleep, some patients developed a sleep apnea syndrome with high sleep Apnea Indices. There was no relation between hypoxic and hypercapnic ventilatory responses during wakefulness and sleep Apnea Indices. But hypoxemia and hypercapnia worsened considerably during REM sleep. Myotonic dystrophy patients with sleep apnea presented increased pulmonary and systemic arterial pressures during sleep. It was also during sleep that arrhythmias were observed.", "contents": "Respiratory and hemodynamic study during wakefulness and sleep in myotonic dystrophy. Six young male patients with grade I (mild) myotonic dystrophy and a complaint of excessive daytime sleepiness were studied during wakefulness and sleep. Pulmonary function tests during wakefulness showed evidence of mild abnormality related to respiratory muscle weakness. During sleep, some patients developed a sleep apnea syndrome with high sleep Apnea Indices. There was no relation between hypoxic and hypercapnic ventilatory responses during wakefulness and sleep Apnea Indices. But hypoxemia and hypercapnia worsened considerably during REM sleep. Myotonic dystrophy patients with sleep apnea presented increased pulmonary and systemic arterial pressures during sleep. It was also during sleep that arrhythmias were observed."}
{"id": "PMID:227022", "title": "Development of sinus arrhythmia during sleeping and waking states in normal infants.", "content": "The development of variability in heart rate (HR) due to respiration (sinus arrhythmia; SA) has been examined in normal infants from birth through the first 6 months of life. Two aspects of HR variation were examined: the absolute variation at the median respiratory frequency, or extent of sinus arrhythmia (XSA), and the degree to which HR follows respiration regardless of the absolute amount of variation, or coherence of sinus arrhythmia (CSA). Extent of sinus arrhythmia tended to be highest in quiet sleep (QS), lower in active or REM sleep (AS), and lowest in waking (AW), especially after 2 months of age. Extent declined at 1 month of age in QS, but rose over the first 6-month period in all states. During this same period, CSA was also highest in QS, lower in AS, and lowest in AW. Coherence in QS also declined at 1 month and rose between 1 and 6 months; however, no age effects were found in other states. Heart rate was negatively correlated with XSA, but less so with CSA. Sleep state appears to have a significant effect on cardiorespiratory coupling, and this coupling undergoes dramatic changes at 1 month in QS.", "contents": "Development of sinus arrhythmia during sleeping and waking states in normal infants. The development of variability in heart rate (HR) due to respiration (sinus arrhythmia; SA) has been examined in normal infants from birth through the first 6 months of life. Two aspects of HR variation were examined: the absolute variation at the median respiratory frequency, or extent of sinus arrhythmia (XSA), and the degree to which HR follows respiration regardless of the absolute amount of variation, or coherence of sinus arrhythmia (CSA). Extent of sinus arrhythmia tended to be highest in quiet sleep (QS), lower in active or REM sleep (AS), and lowest in waking (AW), especially after 2 months of age. Extent declined at 1 month of age in QS, but rose over the first 6-month period in all states. During this same period, CSA was also highest in QS, lower in AS, and lowest in AW. Coherence in QS also declined at 1 month and rose between 1 and 6 months; however, no age effects were found in other states. Heart rate was negatively correlated with XSA, but less so with CSA. Sleep state appears to have a significant effect on cardiorespiratory coupling, and this coupling undergoes dramatic changes at 1 month in QS."}
{"id": "PMID:227023", "title": "Upper airway function during sleep and wakefulness: experimental studies on normal and anesthetized cats.", "content": "Normal (N = 6) and anesthetized (N = 70) cats were used to study the laryngeal abductors, the posterior cricoarytenoid (PCA) muscles, during sleep and wakefulness and to investigate sites within the brainstem that influenced PCA and diaphragmatic activity. The findings were as follows: 1. During wakefulness, PCA activity occurred throughout the respiratory cycle but was most intense during inspiration. Both expiratory and inspiratory PCA activity declined during sleep--the former more so than the latter. The decline in abductor activity was maximal in REM sleep. 2. Barbiturate anesthesia, according to the dosage, produced PCA activity patterns characteristic of either wakefulness or sleep. 3. The brainstem between A4 and P14 was mapped with stimulating electrodes. Rostral brainstem sites showed predominantly facilitatory effects of PCA activity; caudal sites produced predominantly blocking effects. 4. PCA facilitation consisted of (a) an increase in the duration of the PCA burst, (b) and increase in the discharge frequency of the PCA motor units, and (c) a recruitment of larger motor units. PCA blocking effects were the opposite, i.e., burst durations were shortened and motor units were decruited. 5. Facilitatory sites produced clear change in intensity and duration of PCA activity at stimulation intensities below those necessary to obtain changes in the intensity of diaphragmatic activity. 6. Stimulation of facilitatory sites during expiration caused phase switching to inspiration. In some cases, stimulation during inspiration caused phase switching to expiration. The results are discussed in terms of their implications for the obstructive apneas of sleep and in terms of the neural control of breathing.", "contents": "Upper airway function during sleep and wakefulness: experimental studies on normal and anesthetized cats. Normal (N = 6) and anesthetized (N = 70) cats were used to study the laryngeal abductors, the posterior cricoarytenoid (PCA) muscles, during sleep and wakefulness and to investigate sites within the brainstem that influenced PCA and diaphragmatic activity. The findings were as follows: 1. During wakefulness, PCA activity occurred throughout the respiratory cycle but was most intense during inspiration. Both expiratory and inspiratory PCA activity declined during sleep--the former more so than the latter. The decline in abductor activity was maximal in REM sleep. 2. Barbiturate anesthesia, according to the dosage, produced PCA activity patterns characteristic of either wakefulness or sleep. 3. The brainstem between A4 and P14 was mapped with stimulating electrodes. Rostral brainstem sites showed predominantly facilitatory effects of PCA activity; caudal sites produced predominantly blocking effects. 4. PCA facilitation consisted of (a) an increase in the duration of the PCA burst, (b) and increase in the discharge frequency of the PCA motor units, and (c) a recruitment of larger motor units. PCA blocking effects were the opposite, i.e., burst durations were shortened and motor units were decruited. 5. Facilitatory sites produced clear change in intensity and duration of PCA activity at stimulation intensities below those necessary to obtain changes in the intensity of diaphragmatic activity. 6. Stimulation of facilitatory sites during expiration caused phase switching to inspiration. In some cases, stimulation during inspiration caused phase switching to expiration. The results are discussed in terms of their implications for the obstructive apneas of sleep and in terms of the neural control of breathing."}
{"id": "PMID:227024", "title": "Induction and resetting of REM sleep rhythm in normal man by arecholine: blockade by scopolamine.", "content": "Arecholine, a cholinergic muscarinic agonist, was administered intravenously 35 min after sleep onset in eight normal volunteers who had been pretreated with either methscopolamine or scopolamine, muscarinic receptor blockers that do not and do cross the blood--brain barrier, respectively. Following pretreatment with methscopolamine, arecholine shortened the REM latency and increased the number of REM periods without altering the duration of individual REM periods or altering the REM--REM intervals. Pretreatment with scopolamine blocked the effects of arecholine. The results support the hypothesis that cholinergic muscarinic mechanisms are involved in the timing but not the duration of REM sleep.", "contents": "Induction and resetting of REM sleep rhythm in normal man by arecholine: blockade by scopolamine. Arecholine, a cholinergic muscarinic agonist, was administered intravenously 35 min after sleep onset in eight normal volunteers who had been pretreated with either methscopolamine or scopolamine, muscarinic receptor blockers that do not and do cross the blood--brain barrier, respectively. Following pretreatment with methscopolamine, arecholine shortened the REM latency and increased the number of REM periods without altering the duration of individual REM periods or altering the REM--REM intervals. Pretreatment with scopolamine blocked the effects of arecholine. The results support the hypothesis that cholinergic muscarinic mechanisms are involved in the timing but not the duration of REM sleep."}
{"id": "PMID:227026", "title": "The single-mindedness and isolation of dreams.", "content": "Dreams are descirbed as \"single-minded,\" meaning that they tend to be unaccompanied by other, simultaneous streams of thought and imagery. Four manifestations of single-mindedness are discussed: (1) the absence of a reflective awareness that one is dreaming while the dream is in progress; (2) the absence of alternative images and thoughts while attending to the primary dream content; (3) the tendency for dream content to stay on a single thematic track; (4) the absence of a set to remember the dream while it is in progress. This isolation of dream content, from other thought systems is then considered as but one manifestation of a more generalized relative isolation of dream content, which includes isolation from presleep stimuli, contemporaneous stimuli, organismic state, and autonomic and motor activity. Some of the implications of dream isolation for dream psychophysiology and theories of dreaming are outlined.", "contents": "The single-mindedness and isolation of dreams. Dreams are descirbed as \"single-minded,\" meaning that they tend to be unaccompanied by other, simultaneous streams of thought and imagery. Four manifestations of single-mindedness are discussed: (1) the absence of a reflective awareness that one is dreaming while the dream is in progress; (2) the absence of alternative images and thoughts while attending to the primary dream content; (3) the tendency for dream content to stay on a single thematic track; (4) the absence of a set to remember the dream while it is in progress. This isolation of dream content, from other thought systems is then considered as but one manifestation of a more generalized relative isolation of dream content, which includes isolation from presleep stimuli, contemporaneous stimuli, organismic state, and autonomic and motor activity. Some of the implications of dream isolation for dream psychophysiology and theories of dreaming are outlined."}
{"id": "PMID:227028", "title": "Chronic primary insomnia: possible physiopathological involvement of slow wave sleep deficiency.", "content": "This study was designed to compare the sleep of a carefully selected group of patients with chronic primary insomnia toage- and sex-matched controls, in order to investigate the possible physiopathological role of slow wave sleep deficiency in this disturbance. In addition, the effect of age on normal sleep was studied in a group of 40 normal subjects. Sleep was recorded in the laboratory and automatically scored with an electronic system already described. The general trends of sleep stages were computed. Aging in normal subjects was characterized by a sharp decrease of stage 4, but a good stability of stage 3. Insomniacs' sleep showed a sleep-waking imbalance and a marked deficiency in stages 3 and 4. This deficiency seems to be similar to the age effect in normals, but more accentuated; it cannot be attributed merely to increased pressure of wakefulness. We suggest that slow wave sleep is involved in sleep induction and maintenance, and that its deficiency is linked to the fragility of sleep in chronic primary insomnia.", "contents": "Chronic primary insomnia: possible physiopathological involvement of slow wave sleep deficiency. This study was designed to compare the sleep of a carefully selected group of patients with chronic primary insomnia toage- and sex-matched controls, in order to investigate the possible physiopathological role of slow wave sleep deficiency in this disturbance. In addition, the effect of age on normal sleep was studied in a group of 40 normal subjects. Sleep was recorded in the laboratory and automatically scored with an electronic system already described. The general trends of sleep stages were computed. Aging in normal subjects was characterized by a sharp decrease of stage 4, but a good stability of stage 3. Insomniacs' sleep showed a sleep-waking imbalance and a marked deficiency in stages 3 and 4. This deficiency seems to be similar to the age effect in normals, but more accentuated; it cannot be attributed merely to increased pressure of wakefulness. We suggest that slow wave sleep is involved in sleep induction and maintenance, and that its deficiency is linked to the fragility of sleep in chronic primary insomnia."}
{"id": "PMID:227029", "title": "Amitriptyline and EEG sleep in depressed patients: I. Drug effect.", "content": "The paucity of studies on the tricyclic antidepressants led us to conduct an investigation on 30 drug-free patients treated with amitryptyline in a double-blind protocol over a 4-week period. Consistent with previous reports, there was an immediate REM suppression on 50 mg, which was more pronounced at the 100-mg level. However, no significant incremental changes were noticed on 150 or 200 mg with regard to REM sleep suppression. Drug administration was associated with changes in other sleep variables such as stage 1 percent, stage 2 percent, and various measures of sleep continuity. The incomplete tolerance of the drug on certain REM sleep variables enhances our understanding of amitryptyline effects on the EEG sleep of depressed patients.", "contents": "Amitriptyline and EEG sleep in depressed patients: I. Drug effect. The paucity of studies on the tricyclic antidepressants led us to conduct an investigation on 30 drug-free patients treated with amitryptyline in a double-blind protocol over a 4-week period. Consistent with previous reports, there was an immediate REM suppression on 50 mg, which was more pronounced at the 100-mg level. However, no significant incremental changes were noticed on 150 or 200 mg with regard to REM sleep suppression. Drug administration was associated with changes in other sleep variables such as stage 1 percent, stage 2 percent, and various measures of sleep continuity. The incomplete tolerance of the drug on certain REM sleep variables enhances our understanding of amitryptyline effects on the EEG sleep of depressed patients."}
{"id": "PMID:227030", "title": "Relationship of arousal threshold to sleep stage distribution and subjective estimates of depth and quality of sleep.", "content": "The relationship of arousal threshold, amounts of various sleep stages, and subjective rating of sleep was studied in two separate experiments involving 7 and 26 young adult subjects, respectively. Electroencephalographic sleep stage data, subjective response data, and arousal threshold data were collected over a series of nights in the sleep laboratory. Only nonsignificant relationships were found between magnitude of arousal threshold and amounts of various sleep stages or subjective rating of sleep quality in between-subjects analyses. However, when the nights representing extremes in arousal threshold were examined within-subject, it was found that nights of high threshold were accompanied by subjective reports of significantly better sleep in both studies and by a significant decrease in the amount of stage W in one study. Arousal threshold was not related to subjective depth of sleep in either study. Rather, subjective ratings of depth of sleep were significantly related to the amount of EEG-defined wakefulness and stage 1.", "contents": "Relationship of arousal threshold to sleep stage distribution and subjective estimates of depth and quality of sleep. The relationship of arousal threshold, amounts of various sleep stages, and subjective rating of sleep was studied in two separate experiments involving 7 and 26 young adult subjects, respectively. Electroencephalographic sleep stage data, subjective response data, and arousal threshold data were collected over a series of nights in the sleep laboratory. Only nonsignificant relationships were found between magnitude of arousal threshold and amounts of various sleep stages or subjective rating of sleep quality in between-subjects analyses. However, when the nights representing extremes in arousal threshold were examined within-subject, it was found that nights of high threshold were accompanied by subjective reports of significantly better sleep in both studies and by a significant decrease in the amount of stage W in one study. Arousal threshold was not related to subjective depth of sleep in either study. Rather, subjective ratings of depth of sleep were significantly related to the amount of EEG-defined wakefulness and stage 1."}
{"id": "PMID:227031", "title": "The forty-eight hour day.", "content": "Four normal young adult male subjects were evaluated in a systematically imposed regime of 32 hr of wakefulness and 16 hr of sleep time in an environment free from time cues. Electroencephalographic and electrooculographic recordings were made continuously during the experiment, which lasted for 10 complete cycles. Sleep efficiency was assessed by determining the percentage of sleep time during the assigned sleep period. The average sleep efficiency for the experimental period was 77%. Results, in general, conformed to earlier findings of non-24 hr schedules of sleep and waking: the overall sleep system remains relatively stable across a variety of scheduled variations; however, utilization of the sleep period becomes less efficient as the schedule increasingly deviates from the normal approximately 16 hr wakefulness/8 hr sleep schedule.", "contents": "The forty-eight hour day. Four normal young adult male subjects were evaluated in a systematically imposed regime of 32 hr of wakefulness and 16 hr of sleep time in an environment free from time cues. Electroencephalographic and electrooculographic recordings were made continuously during the experiment, which lasted for 10 complete cycles. Sleep efficiency was assessed by determining the percentage of sleep time during the assigned sleep period. The average sleep efficiency for the experimental period was 77%. Results, in general, conformed to earlier findings of non-24 hr schedules of sleep and waking: the overall sleep system remains relatively stable across a variety of scheduled variations; however, utilization of the sleep period becomes less efficient as the schedule increasingly deviates from the normal approximately 16 hr wakefulness/8 hr sleep schedule."}
{"id": "PMID:227032", "title": "Membrane potential of spinal motoneurons during natural sleep in cats.", "content": "The membrane potential of spinal motoneurons was recorded during wakefulness, NREM sleep, and REM sleep in minimally restrained, behaving cats. At the onset of sleep, the membrane potential generally increased in polarization in rough proportion to time spent asleep. During the postural atonia of REM sleep, the membrane potential of all motoneurons was tonically hyperpolarized. Antecedents of NREM sleep electromyographic suppressions, and REM sleep myoclonic twitches were seen as transient hyperpolarizations and depolarizations, respectively.", "contents": "Membrane potential of spinal motoneurons during natural sleep in cats. The membrane potential of spinal motoneurons was recorded during wakefulness, NREM sleep, and REM sleep in minimally restrained, behaving cats. At the onset of sleep, the membrane potential generally increased in polarization in rough proportion to time spent asleep. During the postural atonia of REM sleep, the membrane potential of all motoneurons was tonically hyperpolarized. Antecedents of NREM sleep electromyographic suppressions, and REM sleep myoclonic twitches were seen as transient hyperpolarizations and depolarizations, respectively."}
{"id": "PMID:227033", "title": "The sleep of conjoined twins.", "content": "Conjoined twins with a common heart system and circulatory system were observed during the 14th and 15th days for 11 hr. Sleep, Waking, and Quiet and Active Sleep were recorded in minute intervals. Clear independence of sleep and waking was manifest, and total independence of Quiet and Active sleep was noted.", "contents": "The sleep of conjoined twins. Conjoined twins with a common heart system and circulatory system were observed during the 14th and 15th days for 11 hr. Sleep, Waking, and Quiet and Active Sleep were recorded in minute intervals. Clear independence of sleep and waking was manifest, and total independence of Quiet and Active sleep was noted."}
{"id": "PMID:227036", "title": "[Evaluation of initial supervised and integrated treatment of tuberculosis].", "content": "The operational and technical efficiencies were evaluated, of the initial, intermittently administered chemotherapy, supervised and integrated by the general medical network. The treatment was applied in 160 patients detected in 53 rural medical districts. It was noted that under the operational aspect the treatment was applied in 100% of the eligible patients, and administration of all the necessary doses was achieved in 91,6% of the patients. Bacteriological negativation by the direct examination was obtained after three months and negative cultures were obtained in 93,3% of the patients at three months and in 97,4% of all patients after 9 and 12 months. Closure (filling) of the cavities was obtained in 75,4% of the cases after three months of treatment, and in 87,7% of all cases after 9 and 12 months. Finally the technical efficiency was completed by an assessment of the socio-professional recovery, that was achieved in 91,8% of the cases.", "contents": "[Evaluation of initial supervised and integrated treatment of tuberculosis]. The operational and technical efficiencies were evaluated, of the initial, intermittently administered chemotherapy, supervised and integrated by the general medical network. The treatment was applied in 160 patients detected in 53 rural medical districts. It was noted that under the operational aspect the treatment was applied in 100% of the eligible patients, and administration of all the necessary doses was achieved in 91,6% of the patients. Bacteriological negativation by the direct examination was obtained after three months and negative cultures were obtained in 93,3% of the patients at three months and in 97,4% of all patients after 9 and 12 months. Closure (filling) of the cavities was obtained in 75,4% of the cases after three months of treatment, and in 87,7% of all cases after 9 and 12 months. Finally the technical efficiency was completed by an assessment of the socio-professional recovery, that was achieved in 91,8% of the cases."}
{"id": "PMID:227035", "title": "[Strictly supervised antitubercular chemotherapy in district and plant medical dispensaries in the city of Craiova].", "content": "The mode of administration of chemotherapy is evaluated, in conditions of integration, and under strict supervision, in tuberculosis patients in 12 medical dispensaries and in 6 enterprise dispensaries from Craiova over a period of one year. A total of 88,54 +/- 17,99 per cent of the number of programmed doses was administered in the territorial medical dispensary, as compared with 81,9 +/- 21,3 per cent in the tuberculosis dispensary. In enterprise dispensaries 97,69 +/- 16,17 per cent of the doses was given effectively, as compared with 78,17 +/- 29,39 per cent of doses given to the same patients in the tuberculosis dispensary. During the sick-leave 92,14 +/- 9,19 per cent of the doses were given, in the medical territorial dispensary as against 86,98 +/- 17,58 per cent in the tuberculosis dispensary. The difference is not significant. After reinsertion 77,53 +/- 24,84 per cent of the programmed doses were administered in the tuberculosis dispensary, 88,2 +/- 19,84 per cent in the territorial medical dispensary and 97,12 +/- 5,66 per cent in the enterprise dispensary. The differences were not significant. The authors conclude that administration of anti-tuberculosis chemotherapy can be perfectly well carried out in integrated conditions in the urban environment, especially in interprise medical units, after reinsertion. The phtysiologist should make a periodical survey in these units in view of securing a strict administration of the treatment regimens.", "contents": "[Strictly supervised antitubercular chemotherapy in district and plant medical dispensaries in the city of Craiova]. The mode of administration of chemotherapy is evaluated, in conditions of integration, and under strict supervision, in tuberculosis patients in 12 medical dispensaries and in 6 enterprise dispensaries from Craiova over a period of one year. A total of 88,54 +/- 17,99 per cent of the number of programmed doses was administered in the territorial medical dispensary, as compared with 81,9 +/- 21,3 per cent in the tuberculosis dispensary. In enterprise dispensaries 97,69 +/- 16,17 per cent of the doses was given effectively, as compared with 78,17 +/- 29,39 per cent of doses given to the same patients in the tuberculosis dispensary. During the sick-leave 92,14 +/- 9,19 per cent of the doses were given, in the medical territorial dispensary as against 86,98 +/- 17,58 per cent in the tuberculosis dispensary. The difference is not significant. After reinsertion 77,53 +/- 24,84 per cent of the programmed doses were administered in the tuberculosis dispensary, 88,2 +/- 19,84 per cent in the territorial medical dispensary and 97,12 +/- 5,66 per cent in the enterprise dispensary. The differences were not significant. The authors conclude that administration of anti-tuberculosis chemotherapy can be perfectly well carried out in integrated conditions in the urban environment, especially in interprise medical units, after reinsertion. The phtysiologist should make a periodical survey in these units in view of securing a strict administration of the treatment regimens."}
{"id": "PMID:227046", "title": "Plasma and synovial fluid cAMP in patients with rheumatoid arthritis.", "content": "cAMP was measured in plasma and synovial fluid from 11 patients suffering from rheumatoid arthritis with a specific protein-binding assay. Plasma and synovial fluid values were 17.0 +/- 6.8 pmol/ml and 8.3 +/- 3.7 pmol/ml, range 5-28 pmol/ml and 5-16 pmol/ml, respectively. No correlation could be established between plasma and synovial fluid levels, plasma and disease activity, or synovial fluid and disease activity, as judged by Lansbury's index. It is concluded that it seems unlikely that synovial fluid cAMP is derived solely from plasma and that no simple relation exists between cAMP in plasma and synovial fluid and total disease activity.", "contents": "Plasma and synovial fluid cAMP in patients with rheumatoid arthritis. cAMP was measured in plasma and synovial fluid from 11 patients suffering from rheumatoid arthritis with a specific protein-binding assay. Plasma and synovial fluid values were 17.0 +/- 6.8 pmol/ml and 8.3 +/- 3.7 pmol/ml, range 5-28 pmol/ml and 5-16 pmol/ml, respectively. No correlation could be established between plasma and synovial fluid levels, plasma and disease activity, or synovial fluid and disease activity, as judged by Lansbury's index. It is concluded that it seems unlikely that synovial fluid cAMP is derived solely from plasma and that no simple relation exists between cAMP in plasma and synovial fluid and total disease activity."}
{"id": "PMID:227047", "title": "Pyrophosphate arthropathy.", "content": "Pyrophosphate arthropathy has a wide spectrum of clinical symptoms and is a common cause of synovitis in the elderly. The acute \"pseudogout\" attack is the most commonly recognized, but chronic synovitis might be just as prevalent. Familial pyrophosphate arthropathy with a dominant autosomal heredity is a rare form, with an earlier debut and a more severe prognosis. Another rare expression of pyrophosphate arthropathy is severe joint destruction. The cause of pyrophosphate arthropathy is still unknown. Both individual reactivity and crystal properties determine the intensity of the inflammatory response to crystals.", "contents": "Pyrophosphate arthropathy. Pyrophosphate arthropathy has a wide spectrum of clinical symptoms and is a common cause of synovitis in the elderly. The acute \"pseudogout\" attack is the most commonly recognized, but chronic synovitis might be just as prevalent. Familial pyrophosphate arthropathy with a dominant autosomal heredity is a rare form, with an earlier debut and a more severe prognosis. Another rare expression of pyrophosphate arthropathy is severe joint destruction. The cause of pyrophosphate arthropathy is still unknown. Both individual reactivity and crystal properties determine the intensity of the inflammatory response to crystals."}
{"id": "PMID:227044", "title": "[Considerations on pleural puncturo biopsy, based on the results of an analysis of 100 samples].", "content": "Results are given on 100 cases in which pleural bioptic puncture (PBP) has been performed for diagnosis purposes. The data given in the study show the large possibilities to apply this method, readily acceptable by patients. The high diagnosis value of PBP method in based on strictly objective criteria. Stress is laid upon the contribution of the method in precising the etiology of pleural fluids, which, up to the application of PBP, were labelled as having an \"undetermined\" etiology. The right therapeutic measures to be taken on precise diagnosis are also stressed in the study.", "contents": "[Considerations on pleural puncturo biopsy, based on the results of an analysis of 100 samples]. Results are given on 100 cases in which pleural bioptic puncture (PBP) has been performed for diagnosis purposes. The data given in the study show the large possibilities to apply this method, readily acceptable by patients. The high diagnosis value of PBP method in based on strictly objective criteria. Stress is laid upon the contribution of the method in precising the etiology of pleural fluids, which, up to the application of PBP, were labelled as having an \"undetermined\" etiology. The right therapeutic measures to be taken on precise diagnosis are also stressed in the study."}
{"id": "PMID:227048", "title": "Effect of hydralazine and dihydralazine on connective tissue and binding to serum protein.", "content": "Hydralazine and dihydralazine, chelators of Fe2+, Fe3+ and Mn2+ ions, inhibited collagen biosynthesis in organ culture of chicken embryo tibiae. Both substances inhibited the in vitro hydroxylation of [14C]Pro-labelled protocollagen by protocollagen proline hydroxylase. A decreased incorporation of [14C]-D-glucosamine into glyco- and/or muco-proteins was found under the effect of the two drugs. Dihydralazine, a cationic compound, was bound to DNA and acid mucopolysaccharides (glycosaminoglycans), forming an insoluble complex. Both substances were bound to serum alpha 2-globulin. Subcutaneous injections of dihydralazine in rats produced a local as well as a general toxic effect.", "contents": "Effect of hydralazine and dihydralazine on connective tissue and binding to serum protein. Hydralazine and dihydralazine, chelators of Fe2+, Fe3+ and Mn2+ ions, inhibited collagen biosynthesis in organ culture of chicken embryo tibiae. Both substances inhibited the in vitro hydroxylation of [14C]Pro-labelled protocollagen by protocollagen proline hydroxylase. A decreased incorporation of [14C]-D-glucosamine into glyco- and/or muco-proteins was found under the effect of the two drugs. Dihydralazine, a cationic compound, was bound to DNA and acid mucopolysaccharides (glycosaminoglycans), forming an insoluble complex. Both substances were bound to serum alpha 2-globulin. Subcutaneous injections of dihydralazine in rats produced a local as well as a general toxic effect."}
{"id": "PMID:227041", "title": "[Aspects of tuberculosis prevention in the industrial environment].", "content": "The dynamics were studied of the tuberculous endemy in a limited area of the Cluj-Napoca District over a period of 5--16 years. An industrial environment was considered in comparison with a non-industrial one in the vicinity. The results show a marked decrease in the incidence of tuberculosis in the industrial environment (from 710 0/0000 in 1961 to 102 3/0000 in 1976), but, at the same time, it was demonstrated that morbidity due to tuberculosis is higher as compared with the non-industrial area (318 0/0000 as compared with 49 0/0000). The importance is discussed, of some particular factors of the industrial environment, such as pneumoconioses -- of which the most important are those due to silica -- which are significant risk factors for tuberculosis. A close cooperation is recommended, between enterprise physicians and pneumophtysiologists working in territorial polyclinics.", "contents": "[Aspects of tuberculosis prevention in the industrial environment]. The dynamics were studied of the tuberculous endemy in a limited area of the Cluj-Napoca District over a period of 5--16 years. An industrial environment was considered in comparison with a non-industrial one in the vicinity. The results show a marked decrease in the incidence of tuberculosis in the industrial environment (from 710 0/0000 in 1961 to 102 3/0000 in 1976), but, at the same time, it was demonstrated that morbidity due to tuberculosis is higher as compared with the non-industrial area (318 0/0000 as compared with 49 0/0000). The importance is discussed, of some particular factors of the industrial environment, such as pneumoconioses -- of which the most important are those due to silica -- which are significant risk factors for tuberculosis. A close cooperation is recommended, between enterprise physicians and pneumophtysiologists working in territorial polyclinics."}
{"id": "PMID:227049", "title": "[Prevention of arteriosclerosis. Current basis].", "content": "Despite the advances in therapy, the high incidence, high mortality, and prematurity of coronary heart disease demonstrate the need for prevention. Measurement of a series of easily determined risk factors permits the early recognition of subjects at risk with remarkable reliability. However, reduction of risk factors affords protection against the illness only if they are causally connected with the disease mechanisms. The major evidence for linking atherosclerosis and its consequences with risk factors is reviewed. Particular attention is focused on serum lipids and the \"lipid theory\", smoking, elevated blood pressure, and physical inactivity, which are, on the basis of current knowledge, not only the most important factors but those most readily influenced by changes in daily living habits. Among the multiple risk factors mention is also made of obesity, diabetes, psychosocial stress, and hereditary predisposition. The probability of a causal relationship between risk factors and disease mechanisms justifies every effort to prevent the development of these precursors, or to treat them prophylactically if already present.", "contents": "[Prevention of arteriosclerosis. Current basis]. Despite the advances in therapy, the high incidence, high mortality, and prematurity of coronary heart disease demonstrate the need for prevention. Measurement of a series of easily determined risk factors permits the early recognition of subjects at risk with remarkable reliability. However, reduction of risk factors affords protection against the illness only if they are causally connected with the disease mechanisms. The major evidence for linking atherosclerosis and its consequences with risk factors is reviewed. Particular attention is focused on serum lipids and the \"lipid theory\", smoking, elevated blood pressure, and physical inactivity, which are, on the basis of current knowledge, not only the most important factors but those most readily influenced by changes in daily living habits. Among the multiple risk factors mention is also made of obesity, diabetes, psychosocial stress, and hereditary predisposition. The probability of a causal relationship between risk factors and disease mechanisms justifies every effort to prevent the development of these precursors, or to treat them prophylactically if already present."}
{"id": "PMID:227050", "title": "[The atopy syndrome].", "content": "Atopy is defined as that familial form of increased reactivity which is characterized by a probably genetically determined, spontaneously occurring preferential production of IgE as a response to the natural exposure to allergens normally present in the environment, and whose clinical manifestation as a disease is additionally dependent on a non-immunologically conditioned increase in reagibility of the tissues. An attempt is made to show how many different factors must cooperate to produce atopic disease, and how these factors are mutually influenced by their actions. The implications of this definition of atopy are discussed with reference to prophylaxis and treatment in clinical practice.", "contents": "[The atopy syndrome]. Atopy is defined as that familial form of increased reactivity which is characterized by a probably genetically determined, spontaneously occurring preferential production of IgE as a response to the natural exposure to allergens normally present in the environment, and whose clinical manifestation as a disease is additionally dependent on a non-immunologically conditioned increase in reagibility of the tissues. An attempt is made to show how many different factors must cooperate to produce atopic disease, and how these factors are mutually influenced by their actions. The implications of this definition of atopy are discussed with reference to prophylaxis and treatment in clinical practice."}
{"id": "PMID:227051", "title": "[Bartter's syndrome, chondrocalcinosis and hypomagnesemia].", "content": "In two cases of Bartter's syndrome with hypomagnesaemia the authors report radiological findings typical of chondrocalcinosis associated with joint symptoms corresponding to this condition. In Bartter's syndrome there is, in addition to hypokalaemic alkalosis, often concomitant magnesium depletion which has marked repercussions with respect to both physiopathology and symptomatology. In particular, hypomagnesaemia could well be important in the pathogenesis of chondrocalcinosis through two simultaneous mechanisms: by reducing the activity of pyrophosphatases and by facilitating the crystallisation of pyrophosphates. These mechanisms could explain the association of Bartter's syndrome and chondrocalcinosis, which is described here for the first time.", "contents": "[Bartter's syndrome, chondrocalcinosis and hypomagnesemia]. In two cases of Bartter's syndrome with hypomagnesaemia the authors report radiological findings typical of chondrocalcinosis associated with joint symptoms corresponding to this condition. In Bartter's syndrome there is, in addition to hypokalaemic alkalosis, often concomitant magnesium depletion which has marked repercussions with respect to both physiopathology and symptomatology. In particular, hypomagnesaemia could well be important in the pathogenesis of chondrocalcinosis through two simultaneous mechanisms: by reducing the activity of pyrophosphatases and by facilitating the crystallisation of pyrophosphates. These mechanisms could explain the association of Bartter's syndrome and chondrocalcinosis, which is described here for the first time."}
{"id": "PMID:227043", "title": "[Epidemic of tuberculosis in a maternity hospital triggered by congenital tuberculosis in a newborn infant].", "content": "The development of several cases of miliary tuberculosis in infants aged 3--4 months, born in the same maternity led to an epidemiological investigation. On this occasion it was discovered that one of the patients that had been discharged immediately after delivery had pulmonary granulia a monthlater. The immature newborn was left in the maternity and died after one month with a diagnosis of \"pulmonary microabscesses\". The histopathologic examination of the lungs showed the presence of necrotic foci without any cellular reaction. Five months after the death of the infant a new examination of a pulmonary fragment was performed and Ziehl-Neelsen staining evidenced a large number of acido-resistant bacilli filling the lung alveoles. It was shown in this way that the infant with tuberculosis was the primary source of infection. All the 8 children that had developed the disease had been hospitalized in the same ward with the sick child. The transmission of the bacilli was done indirectly, through the feeding tubes that had not been sufficiently serilised, and the penetration ronte was the digestive tract. In two cases an otic primary focus was discovered and in one case an intestinal one was found on necropsy.", "contents": "[Epidemic of tuberculosis in a maternity hospital triggered by congenital tuberculosis in a newborn infant]. The development of several cases of miliary tuberculosis in infants aged 3--4 months, born in the same maternity led to an epidemiological investigation. On this occasion it was discovered that one of the patients that had been discharged immediately after delivery had pulmonary granulia a monthlater. The immature newborn was left in the maternity and died after one month with a diagnosis of \"pulmonary microabscesses\". The histopathologic examination of the lungs showed the presence of necrotic foci without any cellular reaction. Five months after the death of the infant a new examination of a pulmonary fragment was performed and Ziehl-Neelsen staining evidenced a large number of acido-resistant bacilli filling the lung alveoles. It was shown in this way that the infant with tuberculosis was the primary source of infection. All the 8 children that had developed the disease had been hospitalized in the same ward with the sick child. The transmission of the bacilli was done indirectly, through the feeding tubes that had not been sufficiently serilised, and the penetration ronte was the digestive tract. In two cases an otic primary focus was discovered and in one case an intestinal one was found on necropsy."}
{"id": "PMID:227054", "title": "Acute reactions to mega ascorbic acid therapy in malignant disease.", "content": "Three cases are described, 2 of Hodgkin's disease and a further case of bronchial carcinoma, where high dosage ascorbic acid treatment appeared to be associated with the development of potentially dangerous symptoms. It is suggested that mega ascorbic acid therapy should be given with caution in malignant disease, with a slow build-up over several days to high levels of dosage.", "contents": "Acute reactions to mega ascorbic acid therapy in malignant disease. Three cases are described, 2 of Hodgkin's disease and a further case of bronchial carcinoma, where high dosage ascorbic acid treatment appeared to be associated with the development of potentially dangerous symptoms. It is suggested that mega ascorbic acid therapy should be given with caution in malignant disease, with a slow build-up over several days to high levels of dosage."}
{"id": "PMID:227055", "title": "Hazards of hepatic artery infusion of streptozocin.", "content": "Three patients with metastatic malignancy received streptozocin by hepatic artery infusion through a percutaneous transfemoral catheter. Two patients developed major arterial thrombosis, from which one died. The other suffered renal damage following displacement of the catheter tip. Possible avoidable risk factors are identified.", "contents": "Hazards of hepatic artery infusion of streptozocin. Three patients with metastatic malignancy received streptozocin by hepatic artery infusion through a percutaneous transfemoral catheter. Two patients developed major arterial thrombosis, from which one died. The other suffered renal damage following displacement of the catheter tip. Possible avoidable risk factors are identified."}
{"id": "PMID:227056", "title": "Phase advance of the circadian sleep-wake cycle as an antidepressant.", "content": "Sleep in depressed patients resembles sleep in normal subjects whose circadian rhythms of temperature and rapid-eye-movement sleep are phase-advanced (shifted earlier) relative to their sleep schedules. If this analogy is relevant to the pathophysiology of depressive illness, advancing the time of sleep and awakening should temporarily compensate for the abnormal timing of depressed patients' circadian rhythms. Four of seven manic-depressive patients studied longitudinally spontaneously advanced their times of awakening (activity onset) as they emerged from the depressive phase of their illness. In a phase-shift experiment, a depressed manic-depressive woman was twice brought out of depression for 2 weeks by advancing her sleep period so that she went to sleep and arose 6 hours earlier than usual. The antidepressant effect of the procedure was temporary and similar in duration to circadian desynchronization induced by jet lag in healthy subjects. This result supports the hypothesis that abnormalities of sleep patterns in some types of depression are due to abnormal internal phase relationships of circadian rhythms.", "contents": "Phase advance of the circadian sleep-wake cycle as an antidepressant. Sleep in depressed patients resembles sleep in normal subjects whose circadian rhythms of temperature and rapid-eye-movement sleep are phase-advanced (shifted earlier) relative to their sleep schedules. If this analogy is relevant to the pathophysiology of depressive illness, advancing the time of sleep and awakening should temporarily compensate for the abnormal timing of depressed patients' circadian rhythms. Four of seven manic-depressive patients studied longitudinally spontaneously advanced their times of awakening (activity onset) as they emerged from the depressive phase of their illness. In a phase-shift experiment, a depressed manic-depressive woman was twice brought out of depression for 2 weeks by advancing her sleep period so that she went to sleep and arose 6 hours earlier than usual. The antidepressant effect of the procedure was temporary and similar in duration to circadian desynchronization induced by jet lag in healthy subjects. This result supports the hypothesis that abnormalities of sleep patterns in some types of depression are due to abnormal internal phase relationships of circadian rhythms."}
{"id": "PMID:227058", "title": "Opiate (Enkephalin) receptors of neuroblastoma cells: occurrence in clusters on the cell surface.", "content": "A bioactive, fluorescent derivative of enkephalin, Tyr-D-Ala-Gly-Phe-Leu-Lys-rhodamine, was used to determine the distribution of opiate receptors in living neuroblastoma cells. The receptors appeared in clusters on the cell surface, and no internalization was detected. No specific fluorescence or clusters were observed in the presence of [D-Ala2, Leu5]enkephalin or at 4 degrees C, and the clusters were much reduced under ionic conditions (that is, with 100 millimolars sodium) that specifically decrease the binding of opiate agonists.", "contents": "Opiate (Enkephalin) receptors of neuroblastoma cells: occurrence in clusters on the cell surface. A bioactive, fluorescent derivative of enkephalin, Tyr-D-Ala-Gly-Phe-Leu-Lys-rhodamine, was used to determine the distribution of opiate receptors in living neuroblastoma cells. The receptors appeared in clusters on the cell surface, and no internalization was detected. No specific fluorescence or clusters were observed in the presence of [D-Ala2, Leu5]enkephalin or at 4 degrees C, and the clusters were much reduced under ionic conditions (that is, with 100 millimolars sodium) that specifically decrease the binding of opiate agonists."}
{"id": "PMID:227059", "title": "A sign inversion mechanism for enzymatic supercoiling of DNA.", "content": "Both the introduction and the removal of supertwists by DNA gyrase change the linking number of DNA in steps of two. This surprising finding provides strong evidence that gyrase acts by a mechanism, called sign inversion, whereby a positive supercoil is directly inverted into a negative one via a transient double-strand break.", "contents": "A sign inversion mechanism for enzymatic supercoiling of DNA. Both the introduction and the removal of supertwists by DNA gyrase change the linking number of DNA in steps of two. This surprising finding provides strong evidence that gyrase acts by a mechanism, called sign inversion, whereby a positive supercoil is directly inverted into a negative one via a transient double-strand break."}
{"id": "PMID:227060", "title": "Cerebral vessels have the capacity to transport sodium and potassium.", "content": "The activity of Na+, K+-activated adenosinetriphosphatase and the uptake of a potassium analog, rubidium, were found to be similar in cerebral microvessels and choroid plexus when measured in vitro. This similarity suggests that sodium and potassium concentrations in the nascent brain extracellular fluid are determined by the same active process that regulates their concentration in nascent cerebrospinal fluid. The brain microvessels may thereby play on active role in brain potassium homeostasis and brain extracellular fluid formation.", "contents": "Cerebral vessels have the capacity to transport sodium and potassium. The activity of Na+, K+-activated adenosinetriphosphatase and the uptake of a potassium analog, rubidium, were found to be similar in cerebral microvessels and choroid plexus when measured in vitro. This similarity suggests that sodium and potassium concentrations in the nascent brain extracellular fluid are determined by the same active process that regulates their concentration in nascent cerebrospinal fluid. The brain microvessels may thereby play on active role in brain potassium homeostasis and brain extracellular fluid formation."}
{"id": "PMID:227061", "title": "Physostigmine and recent memory: effects in young and aged nonhuman primates.", "content": "The effect of physostigmine on recent memory was evaluated in young and aged rhesus monkeys. All aged monkeys had previously shown impaired memory. The performance of the young monkeys treated with physostigmine was similar to that recently reported for young humans--no effects at low doses, some improvement at a restricted range of doses, and deficits at the highest dose. Although the aged subjects also improved at the same general doses, their overall response as a group was much more variable than that of the younger subjects. The performance of some aged monkeys was impaired by low doses that did not affect young monkeys. Continued improvement was observed in some aged monkeys at the highest dose, which typically impaired young monkeys. These variable effects across aged subjects suggest that physostigmine cannot easily or reliably be used as an agent for treating geriatric cognition. Nevertheless, the differential age-related effects suggest that appropriate manipulation of the cholinergic system may eventually be developed to alleviate some of the cognitive impairments suffered by aged subjects.", "contents": "Physostigmine and recent memory: effects in young and aged nonhuman primates. The effect of physostigmine on recent memory was evaluated in young and aged rhesus monkeys. All aged monkeys had previously shown impaired memory. The performance of the young monkeys treated with physostigmine was similar to that recently reported for young humans--no effects at low doses, some improvement at a restricted range of doses, and deficits at the highest dose. Although the aged subjects also improved at the same general doses, their overall response as a group was much more variable than that of the younger subjects. The performance of some aged monkeys was impaired by low doses that did not affect young monkeys. Continued improvement was observed in some aged monkeys at the highest dose, which typically impaired young monkeys. These variable effects across aged subjects suggest that physostigmine cannot easily or reliably be used as an agent for treating geriatric cognition. Nevertheless, the differential age-related effects suggest that appropriate manipulation of the cholinergic system may eventually be developed to alleviate some of the cognitive impairments suffered by aged subjects."}
{"id": "PMID:227066", "title": "[The fight against alcoholism and its consequences in general practice (author's transl)].", "content": "Alcoholism is the number-one social scourge in France today and any means that become available for combating its effects are of the utmost importance. The author used an original approach to the problem by obtaining the co-operation of the family doctors in order to study 60 cases, including 52 men and 8 women, with alcoholism. Clinical symptoms, drinking habits, and in some cases biological test results using Gamma GT were recorded. The patients were then treated with tiapride. Daily family, professional and social activities were always better after treatment with extension of ideation and improved relations with others. Tremor was also greatly diminished. Distate for alcohol was not observed constantly but in some rare cases. Total abstinence was only noted in one case, but reduced alcohol consumption was reported in 50% of the patients. It is true that the product was not associated systematically with psychotherapy which might have made the results more demonstrative, but the objective of the study was to evaluate whether tiapride could be of value by assisting in the fight against alcoholism, and this was confirmed.", "contents": "[The fight against alcoholism and its consequences in general practice (author's transl)]. Alcoholism is the number-one social scourge in France today and any means that become available for combating its effects are of the utmost importance. The author used an original approach to the problem by obtaining the co-operation of the family doctors in order to study 60 cases, including 52 men and 8 women, with alcoholism. Clinical symptoms, drinking habits, and in some cases biological test results using Gamma GT were recorded. The patients were then treated with tiapride. Daily family, professional and social activities were always better after treatment with extension of ideation and improved relations with others. Tremor was also greatly diminished. Distate for alcohol was not observed constantly but in some rare cases. Total abstinence was only noted in one case, but reduced alcohol consumption was reported in 50% of the patients. It is true that the product was not associated systematically with psychotherapy which might have made the results more demonstrative, but the objective of the study was to evaluate whether tiapride could be of value by assisting in the fight against alcoholism, and this was confirmed."}
{"id": "PMID:227062", "title": "[Anatomic pathological aspects of chronic obliterating arteriopathies of the extremities (author's transl)].", "content": "It appears that the classical concept of atherosclerosis cannot be applied indiscriminately to all cases and that it is essentially valid for the aorta and its large branches of predominantly elastic structure. When more peripheral arterial trunks are considered, those of muscular type, the lesions are in great part characterized by a dystrophic fibrosis of the media, associated with a diffuse intimal thickening and with stratified fibro-hyaline plaques narrowing the lumen; the latter are responsible for the circulatory insufficiency and gangrene. Comparative analysis of 50 surgical specimens allow us to conclude that those fibro-hyaline plaques represent progressively stratified parietal thrombi that are populated by myocytes, at the contact of which ultrastructural investigation reveals important phenomena of elastogenesis and elastolysis. Most probably, the myocytes originate from the media, through fenestration within the inner elastic membrane. These facts have more than just a purely speculative interest: they express the great plasticity of the arterial walls and their capacity of adaptation to new hemodynamic and biologic conditions. It is interesting to note that this lesion constantly presents signs of metabolic activity and structural remodeling despite its long standing caracter.", "contents": "[Anatomic pathological aspects of chronic obliterating arteriopathies of the extremities (author's transl)]. It appears that the classical concept of atherosclerosis cannot be applied indiscriminately to all cases and that it is essentially valid for the aorta and its large branches of predominantly elastic structure. When more peripheral arterial trunks are considered, those of muscular type, the lesions are in great part characterized by a dystrophic fibrosis of the media, associated with a diffuse intimal thickening and with stratified fibro-hyaline plaques narrowing the lumen; the latter are responsible for the circulatory insufficiency and gangrene. Comparative analysis of 50 surgical specimens allow us to conclude that those fibro-hyaline plaques represent progressively stratified parietal thrombi that are populated by myocytes, at the contact of which ultrastructural investigation reveals important phenomena of elastogenesis and elastolysis. Most probably, the myocytes originate from the media, through fenestration within the inner elastic membrane. These facts have more than just a purely speculative interest: they express the great plasticity of the arterial walls and their capacity of adaptation to new hemodynamic and biologic conditions. It is interesting to note that this lesion constantly presents signs of metabolic activity and structural remodeling despite its long standing caracter."}
{"id": "PMID:227067", "title": "[Renal lesions in progressive systemic sclerosis. A report on five cases (author's transl)].", "content": "Renal lesions are one of the must serious visceral complications of progressive systemic sclerosis: three of the five cases reported died in anuria within a few weeks. A part from this very severe fulminating form, however, cases in which lesions can be demonstrated by pathological examination may produce much milder clinical and biological signs, though still having the same prognostic significance. They can become worse at any moment, either spontaneously, or more often because of other factors such as corticotherapy or pregnancy. A review of the published literature has shown the exact frequency of these lesions and their two principal modes of progression, in both of which the same basic histological changes of proliferation of the intima of the interlobular and preglomerular arteries are found. Kidney function tests can be used to guage the severity and extent of these vascular lesions. It is much more difficult, however, to determine the nature of the initial mechanism causing these lesions. The vascular lesion could be a primary one or may be secondary to an immunological disorder, the exact nature of which has still to be determined.", "contents": "[Renal lesions in progressive systemic sclerosis. A report on five cases (author's transl)]. Renal lesions are one of the must serious visceral complications of progressive systemic sclerosis: three of the five cases reported died in anuria within a few weeks. A part from this very severe fulminating form, however, cases in which lesions can be demonstrated by pathological examination may produce much milder clinical and biological signs, though still having the same prognostic significance. They can become worse at any moment, either spontaneously, or more often because of other factors such as corticotherapy or pregnancy. A review of the published literature has shown the exact frequency of these lesions and their two principal modes of progression, in both of which the same basic histological changes of proliferation of the intima of the interlobular and preglomerular arteries are found. Kidney function tests can be used to guage the severity and extent of these vascular lesions. It is much more difficult, however, to determine the nature of the initial mechanism causing these lesions. The vascular lesion could be a primary one or may be secondary to an immunological disorder, the exact nature of which has still to be determined."}
{"id": "PMID:227063", "title": "[The role of arterial wall proteoglycan in arteriosclerosis (author's transl)].", "content": "Arteriosclerosis is the consequence of numerous factors which may be studied by inspecting; the composition of blood (cholesterol) and haemostasis, as well as, modifications in the composition and structure of aging arterial-wall tissue. Arterial-tunica cells synthesise in particular, elastin and proteoglycan (mucopolysaccharide-protein complexes) which account for the artery's mechanical and elastic properties. We have shown by biochemical separation and characterization that proteoglycan synthesis is considerably modified in aging arterial tissue. The metabolism of these macromolecules declines. Large aggregates of proteoglycan form. Alterations are observed in the distribution of the different protein-associated long chain polysaccharides, in fatty acids and in calcium bound to these proteoglycans favorising the formation of arteriosclerotic plaques. Studies on the aging of arterial cells in culture also demonstrate these same alterations in proteoglycans.", "contents": "[The role of arterial wall proteoglycan in arteriosclerosis (author's transl)]. Arteriosclerosis is the consequence of numerous factors which may be studied by inspecting; the composition of blood (cholesterol) and haemostasis, as well as, modifications in the composition and structure of aging arterial-wall tissue. Arterial-tunica cells synthesise in particular, elastin and proteoglycan (mucopolysaccharide-protein complexes) which account for the artery's mechanical and elastic properties. We have shown by biochemical separation and characterization that proteoglycan synthesis is considerably modified in aging arterial tissue. The metabolism of these macromolecules declines. Large aggregates of proteoglycan form. Alterations are observed in the distribution of the different protein-associated long chain polysaccharides, in fatty acids and in calcium bound to these proteoglycans favorising the formation of arteriosclerotic plaques. Studies on the aging of arterial cells in culture also demonstrate these same alterations in proteoglycans."}
{"id": "PMID:227068", "title": "[Uretral cytology patterns during pregnancy and post partum period (author's transl)].", "content": "During pregnancy and post partum period, uretral cytology shows qualitative and quantitative changes which may be compared to those of vaginal and urinary cytology. However, as the cellular types or uretral cytology are most numerous, the different patterns are not so uniform and seem to offer a more various picture according to the different hormonal status. The relation between glandular cells and trigonal looking epidermoid cells is essential. The trigonal cells lowering, in favour of glandular cells, is rather linked to hormonal deficiency. These different facts may let us hope a better detection of pregnancy and post-maturity hormonal deficiency.", "contents": "[Uretral cytology patterns during pregnancy and post partum period (author's transl)]. During pregnancy and post partum period, uretral cytology shows qualitative and quantitative changes which may be compared to those of vaginal and urinary cytology. However, as the cellular types or uretral cytology are most numerous, the different patterns are not so uniform and seem to offer a more various picture according to the different hormonal status. The relation between glandular cells and trigonal looking epidermoid cells is essential. The trigonal cells lowering, in favour of glandular cells, is rather linked to hormonal deficiency. These different facts may let us hope a better detection of pregnancy and post-maturity hormonal deficiency."}
{"id": "PMID:227069", "title": "[A controlled double-blind clinical trial of a new association of a wide-spectrum antifungal preparation and a corticoid (author's transl)].", "content": "In a controlled double-blind study, the author has comparatively studied the effectiveness and the safety of econazole and of a combination econazole-triamcinolon topically applied, on inflammatory dermatomycoses. Results on 58 patients are reported. The respective well-known properties of econazole and of triamcinolon are maintained in the combination. Clinical symptoms statistically faster disappear with the combined preparation, during the first days of treatment. In addition, the average treatment duration is shortened when econazole-triamcinolon is applied. The new preparation allows security to the physician as well it makes the patient more comfortable.", "contents": "[A controlled double-blind clinical trial of a new association of a wide-spectrum antifungal preparation and a corticoid (author's transl)]. In a controlled double-blind study, the author has comparatively studied the effectiveness and the safety of econazole and of a combination econazole-triamcinolon topically applied, on inflammatory dermatomycoses. Results on 58 patients are reported. The respective well-known properties of econazole and of triamcinolon are maintained in the combination. Clinical symptoms statistically faster disappear with the combined preparation, during the first days of treatment. In addition, the average treatment duration is shortened when econazole-triamcinolon is applied. The new preparation allows security to the physician as well it makes the patient more comfortable."}
{"id": "PMID:227072", "title": "[Therapeutical evaluation on neoplasia-related pain (author's transl)].", "content": "The antalgic effects of tiapride by IM route are evaluated in a randomized study on 30 patients with different kinds of neoplasia-related pain. Using an average dose of 300 mg/day, the effectiveness was considered as excellent or good in 60% and equivalent to the reference drug. This effect was obtained after 30 minutes and lasted about 4 hours. The results compared closely with the reference drug. Tolerance was good with the rare problem of somnolence.", "contents": "[Therapeutical evaluation on neoplasia-related pain (author's transl)]. The antalgic effects of tiapride by IM route are evaluated in a randomized study on 30 patients with different kinds of neoplasia-related pain. Using an average dose of 300 mg/day, the effectiveness was considered as excellent or good in 60% and equivalent to the reference drug. This effect was obtained after 30 minutes and lasted about 4 hours. The results compared closely with the reference drug. Tolerance was good with the rare problem of somnolence."}
{"id": "PMID:227075", "title": "[Remarks on a satellited Y chromosome (author's transl)].", "content": "A previous report in 1967 on the observation of a satellited Y chromosome found in a french canadian family line is confirmed by the use of the ammoniacal silver procedure which stains selectively the nucleolus organizer regions (NORs) in acrocentric human chromosomes. There is evidence that this peculiar chromosome results from the translocation to the distal end of the Y chromosome long arms of a satellited segment from a D or G autosome.", "contents": "[Remarks on a satellited Y chromosome (author's transl)]. A previous report in 1967 on the observation of a satellited Y chromosome found in a french canadian family line is confirmed by the use of the ammoniacal silver procedure which stains selectively the nucleolus organizer regions (NORs) in acrocentric human chromosomes. There is evidence that this peculiar chromosome results from the translocation to the distal end of the Y chromosome long arms of a satellited segment from a D or G autosome."}
{"id": "PMID:227076", "title": "[The surgical treatment of stomach cancers. A review of 759 operations (author's transl)].", "content": "759 patients were studied, deriving from the Statistics of the Department from the last twenty years and the result of an inquiry sent out to the French members of the Collegium Internationale Chirurgiae Digestival. For 602 tumors of the cardia, the long term results of the upper gastrectomies were, inspite of area of non-invaded lymph nodes for 1/3 of the patients, the same for the two sources of statistics, with almost no survival after the fourth year. On the contrary, however, the percentages of survival of total gastrectomies \"by choice\" are 40 and 31% after five years. As for the cancers of the lower part, the result was not as precise and the apparent or proved non invaded state of lymph nodes during the operation make us rather tend towards a partial gastrectomy. (Combined with a mortality rate inferior to those of total gastrectomies). As for the total of gastric cancers, the total gastrectomies \"by necessity\" (eith by tumor growth or lymph tive therapy in a specialized center permit fifty per cent after five years, for the patients who would have been condemned by any other therapeutical act. The nutritional consequences of the total gastrectomies were studied and permitted to conclude that post operative therapy in a specialized center permit fifty per cent of the patients of work age to take up their professional activities again and, on the whole, sixty five per cent of them to have completely satisfactory independance.", "contents": "[The surgical treatment of stomach cancers. A review of 759 operations (author's transl)]. 759 patients were studied, deriving from the Statistics of the Department from the last twenty years and the result of an inquiry sent out to the French members of the Collegium Internationale Chirurgiae Digestival. For 602 tumors of the cardia, the long term results of the upper gastrectomies were, inspite of area of non-invaded lymph nodes for 1/3 of the patients, the same for the two sources of statistics, with almost no survival after the fourth year. On the contrary, however, the percentages of survival of total gastrectomies \"by choice\" are 40 and 31% after five years. As for the cancers of the lower part, the result was not as precise and the apparent or proved non invaded state of lymph nodes during the operation make us rather tend towards a partial gastrectomy. (Combined with a mortality rate inferior to those of total gastrectomies). As for the total of gastric cancers, the total gastrectomies \"by necessity\" (eith by tumor growth or lymph tive therapy in a specialized center permit fifty per cent after five years, for the patients who would have been condemned by any other therapeutical act. The nutritional consequences of the total gastrectomies were studied and permitted to conclude that post operative therapy in a specialized center permit fifty per cent of the patients of work age to take up their professional activities again and, on the whole, sixty five per cent of them to have completely satisfactory independance."}
{"id": "PMID:227078", "title": "[Cerebral infarction and migrainous attack. Angiographic and CT scan studies (author's transl)].", "content": "A lateral homonymous hemianopia appareared in a 40 years old housewife during a migrainous attack and persisted as sequella. Angiographic study was normal and CT scan showed an area of low density at the right occipital level enhancing with heterogenous aspect after the iodinate injection. The occurrence of a cerebral infarction during a migrainous attack is probably due to numerous factors.", "contents": "[Cerebral infarction and migrainous attack. Angiographic and CT scan studies (author's transl)]. A lateral homonymous hemianopia appareared in a 40 years old housewife during a migrainous attack and persisted as sequella. Angiographic study was normal and CT scan showed an area of low density at the right occipital level enhancing with heterogenous aspect after the iodinate injection. The occurrence of a cerebral infarction during a migrainous attack is probably due to numerous factors."}
{"id": "PMID:227077", "title": "[The treatment of headaches: an open randomized comparative therapeutic study (author's transl)].", "content": "An open, randomized clinical trial was carried out to compare the therapeutic efficacy of two products in the treatment of headaches. A total of 65 patients were prescribed tiapride and a similar number were given dimetotiazine (neuroleptic indicated in migraine and headache). Tiapride was prescribed as 3 tablets a day for the first 24 hours, followed by 1/2 a tablet three times daily. Excellent or good results (improvement of 60% or more), were obtained in 49 patients (75%). Results after dimetotiazine, at the recommended dosage of 2 capsules during the first 24 hours followed by 1 capsule at night, gave 30 excellent or good results (46%). There is a highly significant difference (p less than 0,01) in favour of tiapride. Both products were well-tolerated.", "contents": "[The treatment of headaches: an open randomized comparative therapeutic study (author's transl)]. An open, randomized clinical trial was carried out to compare the therapeutic efficacy of two products in the treatment of headaches. A total of 65 patients were prescribed tiapride and a similar number were given dimetotiazine (neuroleptic indicated in migraine and headache). Tiapride was prescribed as 3 tablets a day for the first 24 hours, followed by 1/2 a tablet three times daily. Excellent or good results (improvement of 60% or more), were obtained in 49 patients (75%). Results after dimetotiazine, at the recommended dosage of 2 capsules during the first 24 hours followed by 1 capsule at night, gave 30 excellent or good results (46%). There is a highly significant difference (p less than 0,01) in favour of tiapride. Both products were well-tolerated."}
{"id": "PMID:227079", "title": "[A case of temporal arteritis accompanied with appearance of \"cold areas\" on the liver scan (author's transl)].", "content": "The authors report a case of temporal arteritis accompanied with appearance of \"cold areas\" on the liver scan, regressing after steroid therapy. This observation confirms the existence of hepatic manifestation in giant cell arteritis and evokes a discussion of their mechanism. A hypothesis of hepatic ischemia is proposed.", "contents": "[A case of temporal arteritis accompanied with appearance of \"cold areas\" on the liver scan (author's transl)]. The authors report a case of temporal arteritis accompanied with appearance of \"cold areas\" on the liver scan, regressing after steroid therapy. This observation confirms the existence of hepatic manifestation in giant cell arteritis and evokes a discussion of their mechanism. A hypothesis of hepatic ischemia is proposed."}
{"id": "PMID:227080", "title": "[Unusual ischemic cord compression by discal hernia (author's transl)].", "content": "The discal hernia are unfrequent in dorsal localization and neurological appearances are deceptive. We report a case with amyotrophic and fasciculations developing a progressive spinal cord amyotrophy aspect. The complementary investigations (gaz myelography and spinal angiography) show the discal hernia in T11-T12 which was operated successfully. The vascular factor role is discussed about semiologic and pathogenic view.", "contents": "[Unusual ischemic cord compression by discal hernia (author's transl)]. The discal hernia are unfrequent in dorsal localization and neurological appearances are deceptive. We report a case with amyotrophic and fasciculations developing a progressive spinal cord amyotrophy aspect. The complementary investigations (gaz myelography and spinal angiography) show the discal hernia in T11-T12 which was operated successfully. The vascular factor role is discussed about semiologic and pathogenic view."}
{"id": "PMID:227082", "title": "[Recent results concerning muscular disorders arising from thyroid gland dysfunction (author's transl)].", "content": "The right number of muscular disorders which may be observed clinically in thyroid dysfunction contrast with the paucity of knowledge concerning the mechanisms of action of the thyroid hormones. Those which have been described allowed the following conclusions to be made: 1) The thyroid hormones simultaneously increase the oxydative phosphorylation in mitochondria and the activation of glycogen phosphorylase. 2) They modify the properties of cell membrane without noticiably changing the cytoplasm (light and electron microscopically). These modifications are concommitant with a reduction in resting membrane potential associated with anomalies of Na+ conductance and Ca+ uptake. 3) The appearance and the number of motor units in each muscle is dependant on the hormonal impregnation. However, these diverses actions do not reveal wether the thyroid hormone receptors are in the muscle or if they act via the intermediary of a neuronal trophic factor.", "contents": "[Recent results concerning muscular disorders arising from thyroid gland dysfunction (author's transl)]. The right number of muscular disorders which may be observed clinically in thyroid dysfunction contrast with the paucity of knowledge concerning the mechanisms of action of the thyroid hormones. Those which have been described allowed the following conclusions to be made: 1) The thyroid hormones simultaneously increase the oxydative phosphorylation in mitochondria and the activation of glycogen phosphorylase. 2) They modify the properties of cell membrane without noticiably changing the cytoplasm (light and electron microscopically). These modifications are concommitant with a reduction in resting membrane potential associated with anomalies of Na+ conductance and Ca+ uptake. 3) The appearance and the number of motor units in each muscle is dependant on the hormonal impregnation. However, these diverses actions do not reveal wether the thyroid hormone receptors are in the muscle or if they act via the intermediary of a neuronal trophic factor."}
{"id": "PMID:227081", "title": "[Asymetrical gonadal dysgenesis. Report of a case (author's transl)].", "content": "The authors report a case of asymetrical gonadal dysgenesis related to 45XO-46XY mosaicism in a 16 year old girl. Delayed, growth and puberty, Turner's dysmorphism without sexual ambiguity and skeletal abnormalities are the main clinical features suggesting the diagnosis. Exploratory laparotomy reveals infantil uterus, bilateral falopian tubes and streak gonads. A right dysgenetic testis is identified on electron microscopic examination. Theories on pathogenesis of this unusual genetic defect are discussed.", "contents": "[Asymetrical gonadal dysgenesis. Report of a case (author's transl)]. The authors report a case of asymetrical gonadal dysgenesis related to 45XO-46XY mosaicism in a 16 year old girl. Delayed, growth and puberty, Turner's dysmorphism without sexual ambiguity and skeletal abnormalities are the main clinical features suggesting the diagnosis. Exploratory laparotomy reveals infantil uterus, bilateral falopian tubes and streak gonads. A right dysgenetic testis is identified on electron microscopic examination. Theories on pathogenesis of this unusual genetic defect are discussed."}
{"id": "PMID:227085", "title": "[Hypercalcemia and osteoclast activating factor (OAF) associated with acute lymphoblastic leukemia (author's transl)].", "content": "The occurence of hypercalcemia appears to be unusual in leukemia. The mechanisms are numerous: secretion of PTH of PTH like substance, prostaglandin E2 or vitamin D like sterols. The reported case is one of lymphoblastic acute leukemia and hypercalcemia associated with osteoclast activating factor secreted by leukemic cells. In this patient the serum levels calcium closely paralleled the course of acute leukemia.", "contents": "[Hypercalcemia and osteoclast activating factor (OAF) associated with acute lymphoblastic leukemia (author's transl)]. The occurence of hypercalcemia appears to be unusual in leukemia. The mechanisms are numerous: secretion of PTH of PTH like substance, prostaglandin E2 or vitamin D like sterols. The reported case is one of lymphoblastic acute leukemia and hypercalcemia associated with osteoclast activating factor secreted by leukemic cells. In this patient the serum levels calcium closely paralleled the course of acute leukemia."}
{"id": "PMID:227086", "title": "[Nephretic colic in patients with arrhythmia (author's transl)].", "content": "The authors relate one case of obstruction by emboly in the renal artery. The diagnosis were too late for conservative surgery. In this case, they insist on the particulary signs of that nephretic colic and they show the diagnosis measures which are able to permit a conservative surgery in urgency.", "contents": "[Nephretic colic in patients with arrhythmia (author's transl)]. The authors relate one case of obstruction by emboly in the renal artery. The diagnosis were too late for conservative surgery. In this case, they insist on the particulary signs of that nephretic colic and they show the diagnosis measures which are able to permit a conservative surgery in urgency."}
{"id": "PMID:227083", "title": "[Present position of radiotherapy in the treatment of lymphomas other than Hodgkin's (author's transl)].", "content": "The authors would remind us that the classification of the hemato-sarcomas is at present being reorganized and that, lymphosarcomas are appearing more and more in the form of disseminated diseases sensitive to chemotherapy as well as radiotherapy. It is highly recommended that first a pre-therapeutic check be carried out in order to classify the disease into one of the five stages before deciding on the therapy. The authors report on the association of radiotherapy and chemotherapy and the role of each as used in their treatment of the disease, at present.", "contents": "[Present position of radiotherapy in the treatment of lymphomas other than Hodgkin's (author's transl)]. The authors would remind us that the classification of the hemato-sarcomas is at present being reorganized and that, lymphosarcomas are appearing more and more in the form of disseminated diseases sensitive to chemotherapy as well as radiotherapy. It is highly recommended that first a pre-therapeutic check be carried out in order to classify the disease into one of the five stages before deciding on the therapy. The authors report on the association of radiotherapy and chemotherapy and the role of each as used in their treatment of the disease, at present."}
{"id": "PMID:227084", "title": "[Report of a new case of purpura due to an IgA (K) - IgG cryoglobulinemia (author's transl)].", "content": "The authors report a new case of purpura due to an IgA (K) - IgG cryoglobulinemia, which is a rare immunological event. They recall the main clinical, etiological and therapeutic data of \"essential mixed cryoglobulinemia\" and compare this observation to other similar cases of the literature.", "contents": "[Report of a new case of purpura due to an IgA (K) - IgG cryoglobulinemia (author's transl)]. The authors report a new case of purpura due to an IgA (K) - IgG cryoglobulinemia, which is a rare immunological event. They recall the main clinical, etiological and therapeutic data of \"essential mixed cryoglobulinemia\" and compare this observation to other similar cases of the literature."}
{"id": "PMID:227088", "title": "[Hereditary chronic pancreatitis: an autosomal dominant disease (author's transl)].", "content": "We have studied a family in which three people, two child and an adult had hereditary pancreatitis. Hereditary pancreatitis is not a common disease. Abdominal pain is usually the first clinical sign in children. The knowledge of the existence of such a disease and familiarity with the family history of the child allow the pediatrician to make the diagnosis as soon as the first crisis appears. Surgery is thus avoided. Our studies show definitively that this disease is hereditary and is autosomal dominant with a strong decrease of the penetrance.", "contents": "[Hereditary chronic pancreatitis: an autosomal dominant disease (author's transl)]. We have studied a family in which three people, two child and an adult had hereditary pancreatitis. Hereditary pancreatitis is not a common disease. Abdominal pain is usually the first clinical sign in children. The knowledge of the existence of such a disease and familiarity with the family history of the child allow the pediatrician to make the diagnosis as soon as the first crisis appears. Surgery is thus avoided. Our studies show definitively that this disease is hereditary and is autosomal dominant with a strong decrease of the penetrance."}
{"id": "PMID:227089", "title": "[Fulminating pneumococcal septicemia (author's transl)].", "content": "Two cases of fulminating pneumococcal septicemia (FSP) are reported, and 47 confirmed cases were discovered after a review of the published literature. The syndrome is that of a malignant infection with fever, collapse, and disseminated intravascular coagulation, with a rapid mortal outcome in most cases. Etiologically, FSP is usually the consequence of functional or anatomical asplenia, and the relative frequency of this affection after splenectomy following trauma confirms this observation. Lack of a splenic filter and a deficiency in the phagocytic system are the reasons for microbial proliferation in the blood, and the lymphocytic defence mechanisms are inactive because of the absence of any focus of infection.", "contents": "[Fulminating pneumococcal septicemia (author's transl)]. Two cases of fulminating pneumococcal septicemia (FSP) are reported, and 47 confirmed cases were discovered after a review of the published literature. The syndrome is that of a malignant infection with fever, collapse, and disseminated intravascular coagulation, with a rapid mortal outcome in most cases. Etiologically, FSP is usually the consequence of functional or anatomical asplenia, and the relative frequency of this affection after splenectomy following trauma confirms this observation. Lack of a splenic filter and a deficiency in the phagocytic system are the reasons for microbial proliferation in the blood, and the lymphocytic defence mechanisms are inactive because of the absence of any focus of infection."}
{"id": "PMID:227090", "title": "[Rotavirus gastro-enteritis in infants (author's transl)].", "content": "Deviation of complement antibodies were studied in 630 hospitalized infants aged from 0 to 4 years suffering from rotavirus gastro-enteritis, over a period of one year. Seroconversion was observed in 30 cases out of the 256 infants in whom 2 serological samples were taken. In 29 cases out of 30, these rotavirus infections occurred in infants under 18 months of age, and they were all seen during ther period from november to march, rotavirus being responsible for one third of the gastro-enteritis cases. A serological study according to age-group in 640 infants gave positive results in 75 per cent (1st semester), 68 per cent (2nd semester), 75 per cent (2nd year), 78 per cent (3rd and 4th years).", "contents": "[Rotavirus gastro-enteritis in infants (author's transl)]. Deviation of complement antibodies were studied in 630 hospitalized infants aged from 0 to 4 years suffering from rotavirus gastro-enteritis, over a period of one year. Seroconversion was observed in 30 cases out of the 256 infants in whom 2 serological samples were taken. In 29 cases out of 30, these rotavirus infections occurred in infants under 18 months of age, and they were all seen during ther period from november to march, rotavirus being responsible for one third of the gastro-enteritis cases. A serological study according to age-group in 640 infants gave positive results in 75 per cent (1st semester), 68 per cent (2nd semester), 75 per cent (2nd year), 78 per cent (3rd and 4th years)."}
{"id": "PMID:227091", "title": "[Sulindac suppositories: treatment of pain in osteoarthritis (author's transl)].", "content": "Thirty one patients with osteoarthritis (29 hips, 16 knees) were submitted to a treatment with sulindac at a daily dose of 200 mg bid suppositories during four weeks. This trial showed that the treatment brought relief of pain in the majority of patients. Compared with others previously prescribed drugs, sulindac was more effective (72%). Sulindac suppositories were well tolerated; only three drop-out because side-effects (gastro intestinal tract: 2, skin 1) have been reported. Sulindac suppositories tolerance was reported as good.", "contents": "[Sulindac suppositories: treatment of pain in osteoarthritis (author's transl)]. Thirty one patients with osteoarthritis (29 hips, 16 knees) were submitted to a treatment with sulindac at a daily dose of 200 mg bid suppositories during four weeks. This trial showed that the treatment brought relief of pain in the majority of patients. Compared with others previously prescribed drugs, sulindac was more effective (72%). Sulindac suppositories were well tolerated; only three drop-out because side-effects (gastro intestinal tract: 2, skin 1) have been reported. Sulindac suppositories tolerance was reported as good."}
{"id": "PMID:227092", "title": "[Dehydratation secondary to infantile acute diarrhea. Physiologic basis and management of parenteral rehydration (author's transl)].", "content": "It is advisable to plan the treatment of every patient according to his clinical and eventually biological data, in order to enhance the efficacy and to lessen the risks of rehydration. This paper begins with a brief review of physiological data and clinical symptoms which make the basis to evaluate the needs of each patient in water and electrolytes. The second part gives some rules of management of the parenteral rehydration, depending on the degree and the type of fluid disturbance either hyper, or iso or hyponatraemic dehydration.", "contents": "[Dehydratation secondary to infantile acute diarrhea. Physiologic basis and management of parenteral rehydration (author's transl)]. It is advisable to plan the treatment of every patient according to his clinical and eventually biological data, in order to enhance the efficacy and to lessen the risks of rehydration. This paper begins with a brief review of physiological data and clinical symptoms which make the basis to evaluate the needs of each patient in water and electrolytes. The second part gives some rules of management of the parenteral rehydration, depending on the degree and the type of fluid disturbance either hyper, or iso or hyponatraemic dehydration."}
{"id": "PMID:227093", "title": "[Measurement of blood chloroquine concentrations during neuromyopathies and toxic retinopathies (author's transl)].", "content": "Blood chloroquine concentrations were measured in 5 patients having complications related to this treatment. No significant differences were noted when compared to controls. Further studies are required however before drawing any definite conclusions. The persistence of fairly high residual levels, several months after stopping treatment, is evidence of chloroquine retention in these patients.", "contents": "[Measurement of blood chloroquine concentrations during neuromyopathies and toxic retinopathies (author's transl)]. Blood chloroquine concentrations were measured in 5 patients having complications related to this treatment. No significant differences were noted when compared to controls. Further studies are required however before drawing any definite conclusions. The persistence of fairly high residual levels, several months after stopping treatment, is evidence of chloroquine retention in these patients."}
{"id": "PMID:227094", "title": "[A case of autochthonous leprosy (author's transl)].", "content": "A case is reported of autochthonous leprosy in a French patient who had never lived in an endemic zone. The disease was of the lepromatous leprosy type and the liver, spleen, skin nerves and muscles were affected. Characteristic findings were Hansen's bacillus in nasal scrapings, a deficiency in cellular immunity, and the presence of cryoglobulins and circulating immune complexes. Autochthonous leprosy which has not been imported, and without signs of direct contagion, appears to be exceptionally rare. The authors review the clinical forms of leprosy and immunological findings.", "contents": "[A case of autochthonous leprosy (author's transl)]. A case is reported of autochthonous leprosy in a French patient who had never lived in an endemic zone. The disease was of the lepromatous leprosy type and the liver, spleen, skin nerves and muscles were affected. Characteristic findings were Hansen's bacillus in nasal scrapings, a deficiency in cellular immunity, and the presence of cryoglobulins and circulating immune complexes. Autochthonous leprosy which has not been imported, and without signs of direct contagion, appears to be exceptionally rare. The authors review the clinical forms of leprosy and immunological findings."}
{"id": "PMID:227095", "title": "[A differential diagnosis of sural phlebitis: popliteal cysts. Value of ultrasonography (author's transl)].", "content": "Two cases are reported of popliteal cysts simulating sural phlebitis, one in a patient with lupus, the other during the course of rheumatoid arthritis. Diagnosis is based upon the following signs: sudden onset of pain, sometimes after effort, and in the knee rather than in the calf, and more especially ecchymosis occurring in the internal supramalleolar region. The decision as to whether anticoagulant treatment should be instituted must be based on the certitude of the diagnosis, and this can be obtained in an atraumatic manner by ultrasonography of the popliteal fossa as shown by iconography.", "contents": "[A differential diagnosis of sural phlebitis: popliteal cysts. Value of ultrasonography (author's transl)]. Two cases are reported of popliteal cysts simulating sural phlebitis, one in a patient with lupus, the other during the course of rheumatoid arthritis. Diagnosis is based upon the following signs: sudden onset of pain, sometimes after effort, and in the knee rather than in the calf, and more especially ecchymosis occurring in the internal supramalleolar region. The decision as to whether anticoagulant treatment should be instituted must be based on the certitude of the diagnosis, and this can be obtained in an atraumatic manner by ultrasonography of the popliteal fossa as shown by iconography."}
{"id": "PMID:227097", "title": "[Prevention of stress ulcers with sulpiride (author's transl)].", "content": "Stress ulcers or hemorrhagic lesions of the digestive tract may arise after multiple or cranial trauma, burns, frostbite, severe operations or intensive care treatment, respiratory of renal failure, or any other severe disorder affecting the body. The risk of a stress ulcer accurring varies from 10 to 50% according to the severity and number of factors involved. Sulpiride was studied to assess its preventive value, in 50 high-risk patients being treated in an intensive care unit for medical or surgical conditions. The dosage was 3 injectable ampoules daily during the whole period of intensive care treatment. Control investigations (endoscopy, gastric aspiration, autopsy in case of death) were carried out in all patients. No gastro-intestinal erosions or ulcers developed in any of the 50 patients, and no signs of intolerance were reported.", "contents": "[Prevention of stress ulcers with sulpiride (author's transl)]. Stress ulcers or hemorrhagic lesions of the digestive tract may arise after multiple or cranial trauma, burns, frostbite, severe operations or intensive care treatment, respiratory of renal failure, or any other severe disorder affecting the body. The risk of a stress ulcer accurring varies from 10 to 50% according to the severity and number of factors involved. Sulpiride was studied to assess its preventive value, in 50 high-risk patients being treated in an intensive care unit for medical or surgical conditions. The dosage was 3 injectable ampoules daily during the whole period of intensive care treatment. Control investigations (endoscopy, gastric aspiration, autopsy in case of death) were carried out in all patients. No gastro-intestinal erosions or ulcers developed in any of the 50 patients, and no signs of intolerance were reported."}
{"id": "PMID:227096", "title": "[External carotid arteriography in Horton's disease. A report on 11 observations (author's transl)].", "content": "Highly selective angiography was used to study eleven cases of Horton's arteritis. The results showed the presence of segmental vascular abnormalities which, though mainly affecting the temporal artery region, were also present in that of the internal maxillary artery. This examination procedure can be of great value by assisting the surgeon in his choice of biopsy sample, which is essential for diagnostic purposes.", "contents": "[External carotid arteriography in Horton's disease. A report on 11 observations (author's transl)]. Highly selective angiography was used to study eleven cases of Horton's arteritis. The results showed the presence of segmental vascular abnormalities which, though mainly affecting the temporal artery region, were also present in that of the internal maxillary artery. This examination procedure can be of great value by assisting the surgeon in his choice of biopsy sample, which is essential for diagnostic purposes."}
{"id": "PMID:227098", "title": "[The lateral atlantoaxial joint involvement in the rheumatoid arthritis. Report of ten cases and review (author's transl)].", "content": "An analysis of ten recent observations of lateral arthritis of C1-C2 during the course of rheumato\u00efd arthritis. This lesion, which is not rare, has charact\u00e9ristic symptoms: localized pain together with occipital (Arnold's) neuralgia and specific blocking of head rotation towards the afflicted side. Frontal per-oral radiography shows joint line lesions most often unilateral, and a displacement of C1 towards the non afflicted side with pseudoinclination of the odonto\u00efd process towards the afflicted side. Sometime more destructive lesions of the lateral masses of the atlas give them a triangular form and this may result eventually in an upwards \"vertical\" displacement of the odonto\u00efd. The pain usually subsides in a few weeks after a conservative treatment with or without temporary immobilisation by a light removable cervical collar but the loss of the homolateral rotation of the head persists. Besides occipital (Arnold's) neuralgia, there seems to be no other neurologic complications; if they follow, it is due to an associated anteroposterior displacement.", "contents": "[The lateral atlantoaxial joint involvement in the rheumatoid arthritis. Report of ten cases and review (author's transl)]. An analysis of ten recent observations of lateral arthritis of C1-C2 during the course of rheumato\u00efd arthritis. This lesion, which is not rare, has charact\u00e9ristic symptoms: localized pain together with occipital (Arnold's) neuralgia and specific blocking of head rotation towards the afflicted side. Frontal per-oral radiography shows joint line lesions most often unilateral, and a displacement of C1 towards the non afflicted side with pseudoinclination of the odonto\u00efd process towards the afflicted side. Sometime more destructive lesions of the lateral masses of the atlas give them a triangular form and this may result eventually in an upwards \"vertical\" displacement of the odonto\u00efd. The pain usually subsides in a few weeks after a conservative treatment with or without temporary immobilisation by a light removable cervical collar but the loss of the homolateral rotation of the head persists. Besides occipital (Arnold's) neuralgia, there seems to be no other neurologic complications; if they follow, it is due to an associated anteroposterior displacement."}
{"id": "PMID:227100", "title": "[Headache following intrathecal therapy in acute leukemia: trial of tiapride as a symptomatic treatment (author's transl)].", "content": "11 patients experienced 40 intrathecal injections of cytotoxic drugs during the treatment of acute leukemia. Tiapride was used as a preventive or curative therapy for headache. Results were found excellent or good in 70% of cases. Frequency and intensity of headache were reduced by half. Tiapride seems more effective in early headache than in cephalalgia occuring later.", "contents": "[Headache following intrathecal therapy in acute leukemia: trial of tiapride as a symptomatic treatment (author's transl)]. 11 patients experienced 40 intrathecal injections of cytotoxic drugs during the treatment of acute leukemia. Tiapride was used as a preventive or curative therapy for headache. Results were found excellent or good in 70% of cases. Frequency and intensity of headache were reduced by half. Tiapride seems more effective in early headache than in cephalalgia occuring later."}
{"id": "PMID:227101", "title": "[Parenteral hyperalimentation in the treatment of esophageal, gastric and intestinal fistulas (author's transl)].", "content": "Parenteral hyperalimentation and complete bowel rest reduce fistula output, and permit sufficient caloric and nitrogen intakes needed for healing. It corrects metabolic and nutritional deficiencies due to digestive fistulas, and allows spontaneous closure of fistulas in two out of three patients. If spontaneous healing is not obtained after six weeks of parenteral alimentation, surgical treatment may be undertaken more safety, as the patient will be in better nutritional condition.", "contents": "[Parenteral hyperalimentation in the treatment of esophageal, gastric and intestinal fistulas (author's transl)]. Parenteral hyperalimentation and complete bowel rest reduce fistula output, and permit sufficient caloric and nitrogen intakes needed for healing. It corrects metabolic and nutritional deficiencies due to digestive fistulas, and allows spontaneous closure of fistulas in two out of three patients. If spontaneous healing is not obtained after six weeks of parenteral alimentation, surgical treatment may be undertaken more safety, as the patient will be in better nutritional condition."}
{"id": "PMID:227102", "title": "[Myospherulosis: a riddle asked by strange bags of marbles. A report of four cases (author's transl)].", "content": "Four cases of \"myospherulosis\" are presented with a review of the thirty cases previously reported in the litterature. The disease is characterized by clusters of spherules, surrounded by a thin membranous bag, within a multicystic reaction of muscular and subcutaneous tissue or of paranasal sinuses. The actual nature of these spherules still remains unknown. Several pathogenic hypothesis are suggested.", "contents": "[Myospherulosis: a riddle asked by strange bags of marbles. A report of four cases (author's transl)]. Four cases of \"myospherulosis\" are presented with a review of the thirty cases previously reported in the litterature. The disease is characterized by clusters of spherules, surrounded by a thin membranous bag, within a multicystic reaction of muscular and subcutaneous tissue or of paranasal sinuses. The actual nature of these spherules still remains unknown. Several pathogenic hypothesis are suggested."}
{"id": "PMID:227103", "title": "[Developed carcinomas of the lower oesophagus with peptic lesions (author's transl)].", "content": "The authors report seven cases of carcinomas of the lower oesophagus with peptic lesions. Based on clinical, endoscopical and histological criteria, they point out these peptic lesions preceded the carcinoma in all the cases certainly or very probably. They emphasize at last two cases where the peptic lesions after a strict supervision during many years, gave place, in spite of it all, to a cancerous transformation.", "contents": "[Developed carcinomas of the lower oesophagus with peptic lesions (author's transl)]. The authors report seven cases of carcinomas of the lower oesophagus with peptic lesions. Based on clinical, endoscopical and histological criteria, they point out these peptic lesions preceded the carcinoma in all the cases certainly or very probably. They emphasize at last two cases where the peptic lesions after a strict supervision during many years, gave place, in spite of it all, to a cancerous transformation."}
{"id": "PMID:227104", "title": "[Study of morbidity according to age and sex in adult persons deceased at hospital (author's transl)].", "content": "Studying morbidity according to age and sex in persons decreased at hospital, the authors point out that many illnesses grow in frequency with age. Very often too, illnesses grow in number with age; but this is not constant. At last, this study allows to state the behaviour of old people before illness and the influence of senescence on the terminal evolution.", "contents": "[Study of morbidity according to age and sex in adult persons deceased at hospital (author's transl)]. Studying morbidity according to age and sex in persons decreased at hospital, the authors point out that many illnesses grow in frequency with age. Very often too, illnesses grow in number with age; but this is not constant. At last, this study allows to state the behaviour of old people before illness and the influence of senescence on the terminal evolution."}
{"id": "PMID:227105", "title": "[Anatomical lesions of the liver and oral contraceptives (author's transl)].", "content": "Based on two cases, the authors recall the anatomical lesions of the liver occurring at times in women using oral contraceptives: jaundice, benign tumors, vascular lesions; and they emphasize more particularly the vascular lesions and their relation with oral contraceptives.", "contents": "[Anatomical lesions of the liver and oral contraceptives (author's transl)]. Based on two cases, the authors recall the anatomical lesions of the liver occurring at times in women using oral contraceptives: jaundice, benign tumors, vascular lesions; and they emphasize more particularly the vascular lesions and their relation with oral contraceptives."}
{"id": "PMID:227106", "title": "[Granular cell myoblastoma or Abrikosov's tumor of the esophagus].", "content": "Granular cell myoblastoma or Abrikossoff's tumor of the esophagus are exceptional: fiveteen cases have been described in the literature. In this work we present the following case: discovery of a sub mucosal tumor during a systematic fibroscopic examination of an anemix patient. Only histological examination was able to make the diagnosis.", "contents": "[Granular cell myoblastoma or Abrikosov's tumor of the esophagus]. Granular cell myoblastoma or Abrikossoff's tumor of the esophagus are exceptional: fiveteen cases have been described in the literature. In this work we present the following case: discovery of a sub mucosal tumor during a systematic fibroscopic examination of an anemix patient. Only histological examination was able to make the diagnosis."}
{"id": "PMID:227107", "title": "[The Vaugirard hospital: radio-anatomo-clinical confrontations (author's transl)].", "content": "Since its foundation in the beginning of this century, the Vaugirard hospital of which the origin is briefly recalled, found its way towards digestive surgery and gastroenterology. This induced the creation, 35 years ago, of the Vaugirard Radio-anatomo-clinical Confrontations, only dedicated to digestive pathology.", "contents": "[The Vaugirard hospital: radio-anatomo-clinical confrontations (author's transl)]. Since its foundation in the beginning of this century, the Vaugirard hospital of which the origin is briefly recalled, found its way towards digestive surgery and gastroenterology. This induced the creation, 35 years ago, of the Vaugirard Radio-anatomo-clinical Confrontations, only dedicated to digestive pathology."}
{"id": "PMID:227108", "title": "[Neurological follow-up of glioblastomas treated by chemotherapy. Therapeutical incidences (author's transl)].", "content": "The authors describe the essential neurological complications observed during the follow-up of glioblastomas treated by sequential chemotherapy. They were studied on the basis of clinical, isotopical, CT scanner and or anatomical data. The most frequent complications are: epilepsy, acute neurological deficiency and intracranial hypertension. The diagnostic significance of the complications are discussed. Usually, they expresse a tumour extension. However, the recurrence presents varied aspects. It can be infiltrating and extensed, multifocal, focal, cystic ou pseudocystic. In the majority of cases the morphological, topographical and evolutional characters can determine the therapeutical attitude.", "contents": "[Neurological follow-up of glioblastomas treated by chemotherapy. Therapeutical incidences (author's transl)]. The authors describe the essential neurological complications observed during the follow-up of glioblastomas treated by sequential chemotherapy. They were studied on the basis of clinical, isotopical, CT scanner and or anatomical data. The most frequent complications are: epilepsy, acute neurological deficiency and intracranial hypertension. The diagnostic significance of the complications are discussed. Usually, they expresse a tumour extension. However, the recurrence presents varied aspects. It can be infiltrating and extensed, multifocal, focal, cystic ou pseudocystic. In the majority of cases the morphological, topographical and evolutional characters can determine the therapeutical attitude."}
{"id": "PMID:227111", "title": "[Three cases of renal artery's aneurysm with high blood pressure (author's transl)].", "content": "The authors report three cases of renal artery's aneurysm that caused high blood pressure. Their surgical treatment led to the cure of this high blood pressure. In one case, were applied ex situ surgery's procedures but with local replantation. Then, the authors argue the connexions between renal artery's aneurysms and high blood pressure as well as the indications for their treatments.", "contents": "[Three cases of renal artery's aneurysm with high blood pressure (author's transl)]. The authors report three cases of renal artery's aneurysm that caused high blood pressure. Their surgical treatment led to the cure of this high blood pressure. In one case, were applied ex situ surgery's procedures but with local replantation. Then, the authors argue the connexions between renal artery's aneurysms and high blood pressure as well as the indications for their treatments."}
{"id": "PMID:227110", "title": "[Major hepatic resections. 74 home cases and general review (author's transl)].", "content": "Reporting 74 home cases and data of recent litterature, the Authors try to take stock of major hepatic resection in 1978. Technical difficulties are recalled. The control of vena cava and major hepatic veins remains critical. So are blood coagulation troubles (6 cases). The technical choice amounts of either the ruled hepatectomy first described by J. L. Lortat-Jacob, or the finger-fracture technique. The latter should be preferred in resection for trauma (faster with healthy liver and on unchanged anatomy). In any other cases, we prefer the ruled technique. So do many authors. Vascular isolation techniques should deserve a larger use cross-clamping techniques are available for huge posterior tumours, in normovolhemic and healthy hearted patients. This procedure is fairly advisable in case of significant hemorragic risks. It might increase the resecavility rate (27). Tight monitoring and heavy material means make it available only in specialized centers. Intra-caval shunts, first conceived for caval and hepatic wounds, are an isolation procedure of choice in trauma and hypovolhemy. A larger experience should make the indications more precise. Advance in hepatectomy should reduce morbidity and mortality rates to those of other major digestive surgery. The post-operative course is studied; hemorrhagic and septic complications head the list. The biliary drainage is discussed: its indications should be consistantly reduced. Coagulation troubles and metabolic problems are analyzed advance in hepatic regeneration is pointed out. Indications of major hepatic resections are studied. It seems they should be spead out.", "contents": "[Major hepatic resections. 74 home cases and general review (author's transl)]. Reporting 74 home cases and data of recent litterature, the Authors try to take stock of major hepatic resection in 1978. Technical difficulties are recalled. The control of vena cava and major hepatic veins remains critical. So are blood coagulation troubles (6 cases). The technical choice amounts of either the ruled hepatectomy first described by J. L. Lortat-Jacob, or the finger-fracture technique. The latter should be preferred in resection for trauma (faster with healthy liver and on unchanged anatomy). In any other cases, we prefer the ruled technique. So do many authors. Vascular isolation techniques should deserve a larger use cross-clamping techniques are available for huge posterior tumours, in normovolhemic and healthy hearted patients. This procedure is fairly advisable in case of significant hemorragic risks. It might increase the resecavility rate (27). Tight monitoring and heavy material means make it available only in specialized centers. Intra-caval shunts, first conceived for caval and hepatic wounds, are an isolation procedure of choice in trauma and hypovolhemy. A larger experience should make the indications more precise. Advance in hepatectomy should reduce morbidity and mortality rates to those of other major digestive surgery. The post-operative course is studied; hemorrhagic and septic complications head the list. The biliary drainage is discussed: its indications should be consistantly reduced. Coagulation troubles and metabolic problems are analyzed advance in hepatic regeneration is pointed out. Indications of major hepatic resections are studied. It seems they should be spead out."}
{"id": "PMID:227112", "title": "[Neonatal diagnosis of hypothyroidism by measurement of TSH levels: results in a series of 1880 cases from the University Hospital Center in Caen (author's transl)].", "content": "Early substitutive hormonal treatment for congenital hypothyroidism is the main factor affecting the prognosis of mental abnormalities. Therapy should be instituted in the first few weeks of life but clinical diagnosis is usually very difficult at this stage and biological criteria have to be used as a basis for establishing the diagnosis during the neonatal period. For this reason, TSH levels were measured in 1880 babies on the 4th day of life. This enabled a diagnosis of thyroid agenesia to be made in a case where no tangible clinical signs were present, and treatment could be started on the 12th day of life. Furthermore, two cases of hypothyroidism from iodine overdosage during amniography were discovered and early treatment instituted. The results of this study, which was limited to only one maternity unit, demonstrate the value of systematic diagnostic procedures for congenital hypothyroidism. It also underlines the danger of iodine overdosage during foetal life which could contra-indicate the use of amniography.", "contents": "[Neonatal diagnosis of hypothyroidism by measurement of TSH levels: results in a series of 1880 cases from the University Hospital Center in Caen (author's transl)]. Early substitutive hormonal treatment for congenital hypothyroidism is the main factor affecting the prognosis of mental abnormalities. Therapy should be instituted in the first few weeks of life but clinical diagnosis is usually very difficult at this stage and biological criteria have to be used as a basis for establishing the diagnosis during the neonatal period. For this reason, TSH levels were measured in 1880 babies on the 4th day of life. This enabled a diagnosis of thyroid agenesia to be made in a case where no tangible clinical signs were present, and treatment could be started on the 12th day of life. Furthermore, two cases of hypothyroidism from iodine overdosage during amniography were discovered and early treatment instituted. The results of this study, which was limited to only one maternity unit, demonstrate the value of systematic diagnostic procedures for congenital hypothyroidism. It also underlines the danger of iodine overdosage during foetal life which could contra-indicate the use of amniography."}
{"id": "PMID:227113", "title": "[Urinary tract infection in urology (author's transl)].", "content": "We studied the rate of infection in 144 pre- and post-operative patients. Before intervention the rate is 21,5% and in the post at the discharge of the patient from the hospital, the rate is 28%.", "contents": "[Urinary tract infection in urology (author's transl)]. We studied the rate of infection in 144 pre- and post-operative patients. Before intervention the rate is 21,5% and in the post at the discharge of the patient from the hospital, the rate is 28%."}
{"id": "PMID:227114", "title": "[Immunologic disturbances in psoriatic arthropathy (author's transl)].", "content": "It was observed in 51 cases of psoriatic arthropathy (PA) an increase of blood IgA and a decrease of IgM, a not significant rise of the level of circulating immune complexes, a positive Waaler-Rose reaction in 9.7% of cases and the presence of antigammaglobulin factors (generally of IgG type) in 55,5% of studied patients. Moreover, it was noted a significant decrease of T lymphocytes as detected by E and \"active\" E rosettes, of EA-gamma rosettes (ox erythrocytes) and an increase of the percentage of high avidity Fc-gamma receptor bearing cells. Lymphocytes responses to mitogens were normal or slightly decreased for Concanavalin A. No correlation was found between the immunological data and the clinical features.", "contents": "[Immunologic disturbances in psoriatic arthropathy (author's transl)]. It was observed in 51 cases of psoriatic arthropathy (PA) an increase of blood IgA and a decrease of IgM, a not significant rise of the level of circulating immune complexes, a positive Waaler-Rose reaction in 9.7% of cases and the presence of antigammaglobulin factors (generally of IgG type) in 55,5% of studied patients. Moreover, it was noted a significant decrease of T lymphocytes as detected by E and \"active\" E rosettes, of EA-gamma rosettes (ox erythrocytes) and an increase of the percentage of high avidity Fc-gamma receptor bearing cells. Lymphocytes responses to mitogens were normal or slightly decreased for Concanavalin A. No correlation was found between the immunological data and the clinical features."}
{"id": "PMID:227115", "title": "[Idiopathic neuroarthropathy in a woman (author's transl)].", "content": "The authors report a case of idiopathic and sporadic neuroarthropathy in a 53 year - old woman and point out the rarety of the disease in women unstead of familial Thevenard disease and diabetic neuroarthropathy.", "contents": "[Idiopathic neuroarthropathy in a woman (author's transl)]. The authors report a case of idiopathic and sporadic neuroarthropathy in a 53 year - old woman and point out the rarety of the disease in women unstead of familial Thevenard disease and diabetic neuroarthropathy."}
{"id": "PMID:227116", "title": "[HLA and amyotrophic lateral sclerosis (author's transl)].", "content": "52 patients with amyotrophic lateral sclerosis and 300 normal subjects were tested for 33 HLA-A, B, C antigens. We did not observe any statistically significant difference in antigenic frequencies between the two groups. The absence of association with HLA in amyotrophic lateral sclerosis is a distinction with multiple sclerosis, which is associated with several HLA antigens.", "contents": "[HLA and amyotrophic lateral sclerosis (author's transl)]. 52 patients with amyotrophic lateral sclerosis and 300 normal subjects were tested for 33 HLA-A, B, C antigens. We did not observe any statistically significant difference in antigenic frequencies between the two groups. The absence of association with HLA in amyotrophic lateral sclerosis is a distinction with multiple sclerosis, which is associated with several HLA antigens."}
{"id": "PMID:227122", "title": "A pragmatic approach to mental health aftercare and partial hospitalization.", "content": "Over recent years, there has been increased attention to providing viable community-based alternatives to inpatient psychiatric care. Although there is increased demand for aftercare or daycare social/psychological community treatment, funding sources also mandate more clearcut and precise demonstrations of therapeutic and program effectiveness. This paper describes a pragmatic new approach to daycare for the emotionally disturbed. The central aspects of this approach are: the behavioral identification of clearcut psychosocial treatment goals, contractual negotiation of treatment plans, a skill remediation approach to treatment and objective evaluation of client improvement. By adopting practical and individually-tailored treatment goals and modalities, and by incorporating objective evaluative criteria into a daycare program's treatment components, it is possible to more accurately assess client improvement.", "contents": "A pragmatic approach to mental health aftercare and partial hospitalization. Over recent years, there has been increased attention to providing viable community-based alternatives to inpatient psychiatric care. Although there is increased demand for aftercare or daycare social/psychological community treatment, funding sources also mandate more clearcut and precise demonstrations of therapeutic and program effectiveness. This paper describes a pragmatic new approach to daycare for the emotionally disturbed. The central aspects of this approach are: the behavioral identification of clearcut psychosocial treatment goals, contractual negotiation of treatment plans, a skill remediation approach to treatment and objective evaluation of client improvement. By adopting practical and individually-tailored treatment goals and modalities, and by incorporating objective evaluative criteria into a daycare program's treatment components, it is possible to more accurately assess client improvement."}
{"id": "PMID:227117", "title": "[Interest of percutaneous biliary drainage following percutaneous transhepatic cholangiography in certain obstructive jaundice (author's transl)].", "content": "In addition to the well-known usefulness of percutaneous transhepatic cholangiography, that procedure demonstrates a supplementary interest in certain special cases of dilated biliary tract when it is associated with a external biliary drainage; that drainage is performed by means of a method designed after Seldinger's percutaneous catheterization. That single two-step procedure is a sparing transient palliative policy for certain types of obstructive jaundice; it also permits a more comfortable survival when surgery cannot be achieved.", "contents": "[Interest of percutaneous biliary drainage following percutaneous transhepatic cholangiography in certain obstructive jaundice (author's transl)]. In addition to the well-known usefulness of percutaneous transhepatic cholangiography, that procedure demonstrates a supplementary interest in certain special cases of dilated biliary tract when it is associated with a external biliary drainage; that drainage is performed by means of a method designed after Seldinger's percutaneous catheterization. That single two-step procedure is a sparing transient palliative policy for certain types of obstructive jaundice; it also permits a more comfortable survival when surgery cannot be achieved."}
{"id": "PMID:227123", "title": "Genetics of cell fusion: human chromosome 10 assignment of a gene (FUSE) that promotes polykaryocyte formation.", "content": "FUSE, a human gene which promotes polykaryocyte formation, has been identified and examined in cocultivation assays between rat XC cells and human-mouse hybrids retaining different combinations of human chromosomes. Polykaryocyte formation was never detected when parental cells of hybrids were cocultivated with XC cells. Somatic genetic synteny analysis employing different hybrid sets demonstrated that FUSE was coexpressed with the chromosome 10 markers glutamate oxaloacetate transaminase (GOTs) and an external membrane protein (EMP-130). Cytogenetic analysis confirmed this assignment to human chromosome 10. FUSE was expressed by hybrids made with both human leukocytes and fibroblasts from several individuals, indicating the gene is found in different tissues and may be ubiquitous. Only XC cells were involved in polykaryocyte formation as demonstrated by 33258 Hoechst staining and the absence of heteropolymers between rat and cell hybrid multimeric enzymes. Evidence suggests that the gene FUSE produces a nondiffusible and noninfectious product that is associated with the human-mouse hybrid surface.", "contents": "Genetics of cell fusion: human chromosome 10 assignment of a gene (FUSE) that promotes polykaryocyte formation. FUSE, a human gene which promotes polykaryocyte formation, has been identified and examined in cocultivation assays between rat XC cells and human-mouse hybrids retaining different combinations of human chromosomes. Polykaryocyte formation was never detected when parental cells of hybrids were cocultivated with XC cells. Somatic genetic synteny analysis employing different hybrid sets demonstrated that FUSE was coexpressed with the chromosome 10 markers glutamate oxaloacetate transaminase (GOTs) and an external membrane protein (EMP-130). Cytogenetic analysis confirmed this assignment to human chromosome 10. FUSE was expressed by hybrids made with both human leukocytes and fibroblasts from several individuals, indicating the gene is found in different tissues and may be ubiquitous. Only XC cells were involved in polykaryocyte formation as demonstrated by 33258 Hoechst staining and the absence of heteropolymers between rat and cell hybrid multimeric enzymes. Evidence suggests that the gene FUSE produces a nondiffusible and noninfectious product that is associated with the human-mouse hybrid surface."}
{"id": "PMID:227124", "title": "Maintenance of replication patterns in human-mouse hybrids retaining only one human chromosome.", "content": "The time of termination of DNA replication of human chromosomes in human-mouse hybrids retaining only one human chromosome was analyzed. Hybrids between SV40-transformed human skin fibroblasts and mouse peritoneal macrophages were used for these studies. Data obtained from hybrids containing only human chromosome 7 or 17 were compared with data from related hybrids containing additional human chromosomes. When either human chromosome 7 or 17 was present alone, it terminated replication at the same stage of the S phase as in hybrids in which other human chromosomes were present (relative to the time of termination of replication of the mouse chromosomes). In comparing the hybrids containing single human chromosomes, it was found that chromosome 17 terminated replication much earlier than chromosome 7. Therefore, the relationship between the replication times of these chromosomes normally observed in human cells was maintained in the hybrids in the absence of all other human chromosomes. The results also indicate that the presence of SV40 gene sequences in chromosomes 7 and 17 did not alter the relative times of termination of replication of those chromosomes.", "contents": "Maintenance of replication patterns in human-mouse hybrids retaining only one human chromosome. The time of termination of DNA replication of human chromosomes in human-mouse hybrids retaining only one human chromosome was analyzed. Hybrids between SV40-transformed human skin fibroblasts and mouse peritoneal macrophages were used for these studies. Data obtained from hybrids containing only human chromosome 7 or 17 were compared with data from related hybrids containing additional human chromosomes. When either human chromosome 7 or 17 was present alone, it terminated replication at the same stage of the S phase as in hybrids in which other human chromosomes were present (relative to the time of termination of replication of the mouse chromosomes). In comparing the hybrids containing single human chromosomes, it was found that chromosome 17 terminated replication much earlier than chromosome 7. Therefore, the relationship between the replication times of these chromosomes normally observed in human cells was maintained in the hybrids in the absence of all other human chromosomes. The results also indicate that the presence of SV40 gene sequences in chromosomes 7 and 17 did not alter the relative times of termination of replication of those chromosomes."}
{"id": "PMID:227118", "title": "[Ibuprofen in osteo-articular (author's transl)].", "content": "The authors point out the good results which are obtained in osteo-articular pathology, in particular vertebral, with ibuprofen (Brufen 400). Providing that a sufficient dosage is given (1 600 mg - 2 400 mg per day), an obvious and fast favourable effect is noticed in 75% cases. According to these results, tolerance is quite satisfactory.", "contents": "[Ibuprofen in osteo-articular (author's transl)]. The authors point out the good results which are obtained in osteo-articular pathology, in particular vertebral, with ibuprofen (Brufen 400). Providing that a sufficient dosage is given (1 600 mg - 2 400 mg per day), an obvious and fast favourable effect is noticed in 75% cases. According to these results, tolerance is quite satisfactory."}
{"id": "PMID:227136", "title": "Egg drop syndrome, 1976 (EDS'76).", "content": "A description is given of the new clinical condition in fowl now known as EDS 76. This is characterised by the production of thin shelled, soft shelled and shell less eggs by apparently healthy birds. The effects on egg production are seen around 30 weeks of age and are seen either as an apparent fall in production or as a failure to obtain predicted production targets. Haemagglutinating viruses have been isolated from these flocks and evidence from experimental and field investigations suggest these are the aetiological agents of EDS 76. Biochemical and biological studies indicate that these viruses are duck adenoviruses. Epidemiological evidence suggests the virus is egg transmitted and that lateral spread between flocks is not important if care is taken whilst bleeding and vaccinating flocks. It is postulated that this virus may have been introduced into flocks by the use of a contaminated vaccine. Control in Northern Ireland has been by eradication of the virus from the basic breeding stock.", "contents": "Egg drop syndrome, 1976 (EDS'76). A description is given of the new clinical condition in fowl now known as EDS 76. This is characterised by the production of thin shelled, soft shelled and shell less eggs by apparently healthy birds. The effects on egg production are seen around 30 weeks of age and are seen either as an apparent fall in production or as a failure to obtain predicted production targets. Haemagglutinating viruses have been isolated from these flocks and evidence from experimental and field investigations suggest these are the aetiological agents of EDS 76. Biochemical and biological studies indicate that these viruses are duck adenoviruses. Epidemiological evidence suggests the virus is egg transmitted and that lateral spread between flocks is not important if care is taken whilst bleeding and vaccinating flocks. It is postulated that this virus may have been introduced into flocks by the use of a contaminated vaccine. Control in Northern Ireland has been by eradication of the virus from the basic breeding stock."}
{"id": "PMID:227137", "title": "A biochemical and ultrastructural comparison of Triton X-100 models of normal and transformed cells.", "content": "We have compared the two-dimensional gel profiles of Triton models of normal rat kidney (NRK) cells and their Kirsten viral transformant, 442. Several protein differences were detected. The models of the transformed line lacked five acidic polypeptides and possessed a much higher intermediate filament to actin ratio. Scanning microscopy reveals significant ultrastructural differences in these models, with the NRK line exhibiting a much more filamentous structure. In addition, nuclease treatment of NRK models causes a dramatic change in their scanning image while the 442 models are unaffected. Nuclease treated models lack microfilaments and appear to contain only intermediate filaments, although actin is still a prominent protein constituent.", "contents": "A biochemical and ultrastructural comparison of Triton X-100 models of normal and transformed cells. We have compared the two-dimensional gel profiles of Triton models of normal rat kidney (NRK) cells and their Kirsten viral transformant, 442. Several protein differences were detected. The models of the transformed line lacked five acidic polypeptides and possessed a much higher intermediate filament to actin ratio. Scanning microscopy reveals significant ultrastructural differences in these models, with the NRK line exhibiting a much more filamentous structure. In addition, nuclease treatment of NRK models causes a dramatic change in their scanning image while the 442 models are unaffected. Nuclease treated models lack microfilaments and appear to contain only intermediate filaments, although actin is still a prominent protein constituent."}
{"id": "PMID:227138", "title": "Vitamin D-induced coronary atherosclerosis in normolipemic swine: comparison with human disease.", "content": "Coronary atherosclerosis developed in normolipemic swine fed a basal ration supplemented with 125,000 IU, 62,500 IU and 31,250 IU of vitamin D3/kg of diet for 3 months and subsequently only the basal ration for the following 3 months. Lesions consisted of intimal atheromata and calcified internal elastica and caused luminal narrowing. The incidence of atherosclerotic lesions was proportional to the vitamin D3 doses. The present experimentally induced lesions had many morphological features resembling those in coronary arteries from human subjects.", "contents": "Vitamin D-induced coronary atherosclerosis in normolipemic swine: comparison with human disease. Coronary atherosclerosis developed in normolipemic swine fed a basal ration supplemented with 125,000 IU, 62,500 IU and 31,250 IU of vitamin D3/kg of diet for 3 months and subsequently only the basal ration for the following 3 months. Lesions consisted of intimal atheromata and calcified internal elastica and caused luminal narrowing. The incidence of atherosclerotic lesions was proportional to the vitamin D3 doses. The present experimentally induced lesions had many morphological features resembling those in coronary arteries from human subjects."}
{"id": "PMID:227139", "title": "A simple method to determine adenylate cyclase activity in isolated single nephron segments by radioimmunoassay for succinyl adenosine 3',5'-cyclic monophosphate.", "content": "A simple method to determine adenylate cyclase activity in isolated single nephron segments is described. Segments of the proximal convoluted tubule or the cortical collecting tubule were isolated from rabbit kidney slices pretreated with collagenase. After the tubule membranes were made permeable by adding hypotonic medium and freezing-thawing, each sample was incubated at 30 degrees C for 30 min in a medium containing ATP and theophylline. Generated cAMP was succinylated and served for radioimmunoassay. Addition of the incubation medium did not interfere the radioimmunoassay. Recovery of added cAMP was 96%. In the proximal convoluted tubule, either 8 mM NaF or 1 U/ml parathyroid hormone (PTH) markedly stimulated adenylate cyclase activity, but 1 mU/ml arginine vasopressin (AVP) did not. By contrast, in the cortical collecting tubule, either 8 mM NaF or 1 mU/ML AVP markedly stimulated adenylate cyclase activity, but 1 U/ml PTH did not. These data imply that this method is sensitive enough to detect either specific or nonspecific response of adenylate cyclase activity in single nephron segments.", "contents": "A simple method to determine adenylate cyclase activity in isolated single nephron segments by radioimmunoassay for succinyl adenosine 3',5'-cyclic monophosphate. A simple method to determine adenylate cyclase activity in isolated single nephron segments is described. Segments of the proximal convoluted tubule or the cortical collecting tubule were isolated from rabbit kidney slices pretreated with collagenase. After the tubule membranes were made permeable by adding hypotonic medium and freezing-thawing, each sample was incubated at 30 degrees C for 30 min in a medium containing ATP and theophylline. Generated cAMP was succinylated and served for radioimmunoassay. Addition of the incubation medium did not interfere the radioimmunoassay. Recovery of added cAMP was 96%. In the proximal convoluted tubule, either 8 mM NaF or 1 U/ml parathyroid hormone (PTH) markedly stimulated adenylate cyclase activity, but 1 mU/ml arginine vasopressin (AVP) did not. By contrast, in the cortical collecting tubule, either 8 mM NaF or 1 mU/ML AVP markedly stimulated adenylate cyclase activity, but 1 U/ml PTH did not. These data imply that this method is sensitive enough to detect either specific or nonspecific response of adenylate cyclase activity in single nephron segments."}
{"id": "PMID:227140", "title": "A lymphoblastoid cell line from an adenosine deaminase deficient patient established by Epstein-Barr virus.", "content": "Lymphoblastoid cell lines from a patient with adenosine deaminase (ADA) deficiency and his parents were established by Epstein-Barr virus (EBV). ADA activity in the lymphoblastoid cells from the patient was not detectable, while the enzyme activity in the cells from his parents was approximately a half level of the controls'. No inhibitor to ADA could be detected in the lymphoblastoid cells from the patient.", "contents": "A lymphoblastoid cell line from an adenosine deaminase deficient patient established by Epstein-Barr virus. Lymphoblastoid cell lines from a patient with adenosine deaminase (ADA) deficiency and his parents were established by Epstein-Barr virus (EBV). ADA activity in the lymphoblastoid cells from the patient was not detectable, while the enzyme activity in the cells from his parents was approximately a half level of the controls'. No inhibitor to ADA could be detected in the lymphoblastoid cells from the patient."}
{"id": "PMID:227141", "title": "Neuromuscular blocking property of minocycline in the rabbit.", "content": "The neuromuscular blocking property of minocycline hydrochloride (MNC) was studied in 12 rabbits. In 2 of 6 animals, MNC, 60-160 mg/kg, alone caused a decrease in twitch tension. During partial neuromuscular blockade produced by a continuous infusion of pancuronium, the intravenous administration of MNC, 20--60 mg/kg, resulted in a dose-dependent decrease in twitch tension in 6 animals. MNC-induced or combined MNC-pancuronium-induced neuromuscular blockade was antagonized by calcium or by neostigmine.", "contents": "Neuromuscular blocking property of minocycline in the rabbit. The neuromuscular blocking property of minocycline hydrochloride (MNC) was studied in 12 rabbits. In 2 of 6 animals, MNC, 60-160 mg/kg, alone caused a decrease in twitch tension. During partial neuromuscular blockade produced by a continuous infusion of pancuronium, the intravenous administration of MNC, 20--60 mg/kg, resulted in a dose-dependent decrease in twitch tension in 6 animals. MNC-induced or combined MNC-pancuronium-induced neuromuscular blockade was antagonized by calcium or by neostigmine."}
{"id": "PMID:227144", "title": "Free lung cell response after combined exposure to cigarette smoke and industrial dusts.", "content": "Guinea pigs were acutely exposed to different airborne dusts and freshly generated cigarette smoke. The effect was evaluated by counting the number of free lung cells using a lavage method. An exposure to MnO2 and smoke on the same day caused an increase in the number of leukocytes 24 h thereafter. By increasing the time interval between the MnO2 and smoke exposure, the effect gradually disappeared. Al2O2 or SiO2 also caused an increase in the number of leukocytes, whereas TiO2 had no effect. The pathogenesis behind the reaction and the epidemiological implications are discussed.", "contents": "Free lung cell response after combined exposure to cigarette smoke and industrial dusts. Guinea pigs were acutely exposed to different airborne dusts and freshly generated cigarette smoke. The effect was evaluated by counting the number of free lung cells using a lavage method. An exposure to MnO2 and smoke on the same day caused an increase in the number of leukocytes 24 h thereafter. By increasing the time interval between the MnO2 and smoke exposure, the effect gradually disappeared. Al2O2 or SiO2 also caused an increase in the number of leukocytes, whereas TiO2 had no effect. The pathogenesis behind the reaction and the epidemiological implications are discussed."}
{"id": "PMID:227145", "title": "Increased aryl hydrocarbon hydroxylase and prolyl hydroxylase activities in lung organ cultures exposed to benzo[a]pyrene.", "content": "Exposure of neo-natal rat lungs in organ culture to 10--25 microM benzo[a]pyrene (BaP) elevated the activities of aryl hydrocarbon hydroxylase (AHH) and prolyl hydroxylase (PH). Pyrene, a non-carcinogenic hydrocarbon did not elicit this response. Prolyl hydroxylase is an indicator of collagen synthesis and increased PH activity in the lungs reflects increased collagen synthesis. Our studies suggest that the earliest events in BaP-induced lung injury may include altered collagen metabolism.", "contents": "Increased aryl hydrocarbon hydroxylase and prolyl hydroxylase activities in lung organ cultures exposed to benzo[a]pyrene. Exposure of neo-natal rat lungs in organ culture to 10--25 microM benzo[a]pyrene (BaP) elevated the activities of aryl hydrocarbon hydroxylase (AHH) and prolyl hydroxylase (PH). Pyrene, a non-carcinogenic hydrocarbon did not elicit this response. Prolyl hydroxylase is an indicator of collagen synthesis and increased PH activity in the lungs reflects increased collagen synthesis. Our studies suggest that the earliest events in BaP-induced lung injury may include altered collagen metabolism."}
{"id": "PMID:227150", "title": "[NAD+ synthesis in the isolated kidney cell nuclei of dogs after the intravenous administration of amphotericin B].", "content": "A study was made of the synthesis of nicotinamide adenine dinucleotide (NAD+) in the nuclei of kidney cells of dogs under normal conditions and upon the effect of the polyenic antibiotic amphotericin B. An active NAD-pyrophosphorylase has been found in the nuclei of kidney cells. It has been established that a intervenous introduction of amphotericin B stimulates NAD+ production. Amphotericin B also causes a decrease in the amount of histones in the nucleus. In the case of the nuclear membrane damage by a non-ionic detergent Triton X-100, no increase in the synthesis of NAD+ has been observed in the nuclei of kidney cells of animals treated with antibiotics, as opposed to the control ones. Under discussion is a question of a possible mechanism of the effect of polyenic antibiotics on the synthesis and metabolic activity of NAD+.", "contents": "[NAD+ synthesis in the isolated kidney cell nuclei of dogs after the intravenous administration of amphotericin B]. A study was made of the synthesis of nicotinamide adenine dinucleotide (NAD+) in the nuclei of kidney cells of dogs under normal conditions and upon the effect of the polyenic antibiotic amphotericin B. An active NAD-pyrophosphorylase has been found in the nuclei of kidney cells. It has been established that a intervenous introduction of amphotericin B stimulates NAD+ production. Amphotericin B also causes a decrease in the amount of histones in the nucleus. In the case of the nuclear membrane damage by a non-ionic detergent Triton X-100, no increase in the synthesis of NAD+ has been observed in the nuclei of kidney cells of animals treated with antibiotics, as opposed to the control ones. Under discussion is a question of a possible mechanism of the effect of polyenic antibiotics on the synthesis and metabolic activity of NAD+."}
{"id": "PMID:227151", "title": "Natural antilymphoma antibodies in C3Hf mice serum: lack of identity with autoimmune and anti murine leukemia virus antibodies.", "content": "Absorption experiments on C3Hf normal mouse sera followed by cytotoxic tests on EL4 lymphoma cells were done to investigate a possible identity between natural antilymphoma antibodies (NAA) and various types of autoantibodies known to be present in normal mouse sera. Single C3Hf normal sera were also tested both by cytotoxicity on EL4 cells and by radioimmune precipitation assay (RIP) on 125I-labelled AKR ecotropic virus to ascertain whether or not viral antigen are the target structures of the NAA activity. The study provides evidence that NAA coexist with autoanticorpal and antiviral activities although they are distinct entities.", "contents": "Natural antilymphoma antibodies in C3Hf mice serum: lack of identity with autoimmune and anti murine leukemia virus antibodies. Absorption experiments on C3Hf normal mouse sera followed by cytotoxic tests on EL4 lymphoma cells were done to investigate a possible identity between natural antilymphoma antibodies (NAA) and various types of autoantibodies known to be present in normal mouse sera. Single C3Hf normal sera were also tested both by cytotoxicity on EL4 cells and by radioimmune precipitation assay (RIP) on 125I-labelled AKR ecotropic virus to ascertain whether or not viral antigen are the target structures of the NAA activity. The study provides evidence that NAA coexist with autoanticorpal and antiviral activities although they are distinct entities."}
{"id": "PMID:227152", "title": "[Viable cells from human renal cell carcinoma: isolation procedure and analysis of hormone sensitivity (author's transl)].", "content": "An enzymatic procedure for the isolation of metabolically active tumour cells from human renal cell carcinoma is described. The cells were suspended by a multistep incubation procedure of the tissue in the presence of collagenase (10 mg enzyme/g tumour wet weight) dissolved in a calcium-free buffer solution. About 90% of the isolated tumour cells were viable, as judged by routine trypan blue staining. Electron microscopic examination revealed tumour cells in various stages of dedifferentiation. The cells had retained their capability of protein synthesis. In short term experiments the effects of 17 beta-oestradiol and progesterone on the incorporation of [U - C] L-leucine into cellular proteins was studied; Progesterone was found to exhibit a slight tumour antianabolic or catabolic action. A 17 beta-oestradiol-dependent modulation of the rates of protein synthesis was not observed.", "contents": "[Viable cells from human renal cell carcinoma: isolation procedure and analysis of hormone sensitivity (author's transl)]. An enzymatic procedure for the isolation of metabolically active tumour cells from human renal cell carcinoma is described. The cells were suspended by a multistep incubation procedure of the tissue in the presence of collagenase (10 mg enzyme/g tumour wet weight) dissolved in a calcium-free buffer solution. About 90% of the isolated tumour cells were viable, as judged by routine trypan blue staining. Electron microscopic examination revealed tumour cells in various stages of dedifferentiation. The cells had retained their capability of protein synthesis. In short term experiments the effects of 17 beta-oestradiol and progesterone on the incorporation of [U - C] L-leucine into cellular proteins was studied; Progesterone was found to exhibit a slight tumour antianabolic or catabolic action. A 17 beta-oestradiol-dependent modulation of the rates of protein synthesis was not observed."}
{"id": "PMID:227153", "title": "Percutaneous 17 beta-estradiol in treatment of cancer of prostate.", "content": "A natural estrogen, 17 beta-estradiol, was given percutaneously to 21 patients with untreated cancer of the prostate. The follow-up lasted three to six months, and the results of the survey were encouraging. The hormonal controls showed good plasma diffusion of estrogen, a significant drop in plasma testosterone, and decreased hypophyseal secretion as shown by lower follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels. Triglycerides and very low density lipoproteins (VLDL) which are considered to be good indicators of cardiovascular risk were unchanged.", "contents": "Percutaneous 17 beta-estradiol in treatment of cancer of prostate. A natural estrogen, 17 beta-estradiol, was given percutaneously to 21 patients with untreated cancer of the prostate. The follow-up lasted three to six months, and the results of the survey were encouraging. The hormonal controls showed good plasma diffusion of estrogen, a significant drop in plasma testosterone, and decreased hypophyseal secretion as shown by lower follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels. Triglycerides and very low density lipoproteins (VLDL) which are considered to be good indicators of cardiovascular risk were unchanged."}
{"id": "PMID:227154", "title": "Peripheral neuropathy and myopathy. An experimental study of rats on alcohol and variable dietary thiamine.", "content": "The effects of variable dietary thiamine concentrations (deficient, normal, surplus) on the development of alcoholic neuromyopathy in rats exposed for 36 weeks to 10-25% (v/v) ethanol or water (control group) as the sole drinking fluid were studied by histological and electrophysiological methods. Abnormalities in the structure of the sciatic nerve (phagocytosis, myelin abnormalities, increase in nonspecific cholinesterase activity) and tibial muscles (angular atrophic fibers, group atrophy, fibre necrosis) developed more frequently in animals on diets deficient in thiamine than in animals on diets with normal or surplus thiamine, and more frequently in animals drinking alcohol and water than in those drinking water alone. No differences were observed between the different groups in the number of perivascular sympathetic nerves, in the motor nerve conduction velocities and in the muscle fibrillation potentials. Thus, thiamine deficiency, established as a significant reduction of red blood cell transketolase activity, seems to have a deleterious effect on the peripheral nerves and muscles. The effect is enhanced by the simultaneous consumption of ethyl alcohol.", "contents": "Peripheral neuropathy and myopathy. An experimental study of rats on alcohol and variable dietary thiamine. The effects of variable dietary thiamine concentrations (deficient, normal, surplus) on the development of alcoholic neuromyopathy in rats exposed for 36 weeks to 10-25% (v/v) ethanol or water (control group) as the sole drinking fluid were studied by histological and electrophysiological methods. Abnormalities in the structure of the sciatic nerve (phagocytosis, myelin abnormalities, increase in nonspecific cholinesterase activity) and tibial muscles (angular atrophic fibers, group atrophy, fibre necrosis) developed more frequently in animals on diets deficient in thiamine than in animals on diets with normal or surplus thiamine, and more frequently in animals drinking alcohol and water than in those drinking water alone. No differences were observed between the different groups in the number of perivascular sympathetic nerves, in the motor nerve conduction velocities and in the muscle fibrillation potentials. Thus, thiamine deficiency, established as a significant reduction of red blood cell transketolase activity, seems to have a deleterious effect on the peripheral nerves and muscles. The effect is enhanced by the simultaneous consumption of ethyl alcohol."}
{"id": "PMID:227173", "title": "Clonal proliferation of lymphoid and myeloid progenitor cells in patients with hematological abnormalities.", "content": "Myeloid and lymphoid stem cell colony formation (GM-CFU) and L-CFU) was studied in patients with lymphoproliferative diseases, aplastic anemia and other hematological abnormalities. Most patients with acute lymphatic leukemia had low number of L-CFU with decreased or normal GM-CFU, while in Hodgkin's disease and chronic lymphatic leukemia L-CFU growth was very poor with only minor abnormalities of GM-CFU formation. Aplastic anemia was characterized by a decreased GM-CFU and normal L-CFU. Coculture studies suggested that a diminished colony formation may be linked to circulating lymphocytes that inhibit L-CFU as well as the reduction in number of precursor cells.", "contents": "Clonal proliferation of lymphoid and myeloid progenitor cells in patients with hematological abnormalities. Myeloid and lymphoid stem cell colony formation (GM-CFU) and L-CFU) was studied in patients with lymphoproliferative diseases, aplastic anemia and other hematological abnormalities. Most patients with acute lymphatic leukemia had low number of L-CFU with decreased or normal GM-CFU, while in Hodgkin's disease and chronic lymphatic leukemia L-CFU growth was very poor with only minor abnormalities of GM-CFU formation. Aplastic anemia was characterized by a decreased GM-CFU and normal L-CFU. Coculture studies suggested that a diminished colony formation may be linked to circulating lymphocytes that inhibit L-CFU as well as the reduction in number of precursor cells."}
{"id": "PMID:227169", "title": "[Tissue respiratory enzymes in the rat liver in acute blood loss].", "content": "An increase in activity of several dehydrogenases of tricarboxylic acid cycle (NADP-dependent malate dehydrogenase, alpha-ketoglutarate dehydrogenase) was observed in rat liver tissue under conditions of acute hemorrhage. The enzymatic activity was slightly higher in the group of animals with relatively prolonged life-time as compared with those, which lived less than 4 hrs. Activity of cytochrome oxidase was inhilited in the both groups of animals (by 27% and 29%, respectively). The less distinct decrease in both temperature in the group of animals with prolonged life-time might maintain the rate of Krebs cycle substrates oxidation. Activation of respiration in liver tissue under conditions of the hemorrhage is considered as a compensatory reaction tending to improve oxygen utilization in hypoxia. At the same time, inhibition oy cytochrome oxidase demonstrates the impairment of electron transport and decreased rate of energy production in liver mitochondria.", "contents": "[Tissue respiratory enzymes in the rat liver in acute blood loss]. An increase in activity of several dehydrogenases of tricarboxylic acid cycle (NADP-dependent malate dehydrogenase, alpha-ketoglutarate dehydrogenase) was observed in rat liver tissue under conditions of acute hemorrhage. The enzymatic activity was slightly higher in the group of animals with relatively prolonged life-time as compared with those, which lived less than 4 hrs. Activity of cytochrome oxidase was inhilited in the both groups of animals (by 27% and 29%, respectively). The less distinct decrease in both temperature in the group of animals with prolonged life-time might maintain the rate of Krebs cycle substrates oxidation. Activation of respiration in liver tissue under conditions of the hemorrhage is considered as a compensatory reaction tending to improve oxygen utilization in hypoxia. At the same time, inhibition oy cytochrome oxidase demonstrates the impairment of electron transport and decreased rate of energy production in liver mitochondria."}
{"id": "PMID:227170", "title": "[Effect of chemical hepatic carcinogens and noradrenaline on the nucleoside phosphokinase activity of liver cells].", "content": "Distinct increase in activity of uridine kinase and pronounced decrease in thymidine kinase activity were observed in cell-free extracts of rat liver tissue at early stages of hepatocarcinogenesis caused by administration of N-nitrose diethylamine and 2-acetyl aminofluorene. Exogenous noradrepaline did not affect the altered activity of thymidine kinase but stimulated the effect of N-nitrose diethylamine and lowered the effect of 2-acetyl aminofluorene on the urindine kinase activity. Adrenergic neurotransmitters appear to influence the cell proliferation due to modification of the enzymes participating in the synthesis of nucleic acid precursors.", "contents": "[Effect of chemical hepatic carcinogens and noradrenaline on the nucleoside phosphokinase activity of liver cells]. Distinct increase in activity of uridine kinase and pronounced decrease in thymidine kinase activity were observed in cell-free extracts of rat liver tissue at early stages of hepatocarcinogenesis caused by administration of N-nitrose diethylamine and 2-acetyl aminofluorene. Exogenous noradrepaline did not affect the altered activity of thymidine kinase but stimulated the effect of N-nitrose diethylamine and lowered the effect of 2-acetyl aminofluorene on the urindine kinase activity. Adrenergic neurotransmitters appear to influence the cell proliferation due to modification of the enzymes participating in the synthesis of nucleic acid precursors."}
{"id": "PMID:227171", "title": "[Effect of carbostimulin and its mixture with vitamin D3 on the mineralization process of the bone callus in rabbits].", "content": "Mineralization of rabbit bone callus was studied within 15 days after resection of the upper part of radius bone inder conditions of treatment with carbostimuline and its mixture with vitamin D3. Content of calcium in the bone regenerate was increased by 40.8% after administration of carbostimuline and--by 70.5% after treatment with mixture containing vitamin D3. These preparations caused only slight effects on the phosphorus content. Dry residue in the regenerate os f animals, treated with the preparations, was increased approximately 2-fold (43% and 23%, respectively, p less than or equal to 0.001) as compared with control group. Content of citric acid was distinctly higher in the bone tissue of the treated animals. Within 15 days after the operation content of sialic acids wanormalized in blood serum of the animals. The data obtained were corroborated by X-ray and histologic examinations.", "contents": "[Effect of carbostimulin and its mixture with vitamin D3 on the mineralization process of the bone callus in rabbits]. Mineralization of rabbit bone callus was studied within 15 days after resection of the upper part of radius bone inder conditions of treatment with carbostimuline and its mixture with vitamin D3. Content of calcium in the bone regenerate was increased by 40.8% after administration of carbostimuline and--by 70.5% after treatment with mixture containing vitamin D3. These preparations caused only slight effects on the phosphorus content. Dry residue in the regenerate os f animals, treated with the preparations, was increased approximately 2-fold (43% and 23%, respectively, p less than or equal to 0.001) as compared with control group. Content of citric acid was distinctly higher in the bone tissue of the treated animals. Within 15 days after the operation content of sialic acids wanormalized in blood serum of the animals. The data obtained were corroborated by X-ray and histologic examinations."}
{"id": "PMID:227176", "title": "Conceptual and methodological considerations towards the development of computer-controlled research on the electro-physiology of sleep.", "content": "A critical discussion of the visual scoring approach to the measurement of sleep electrophysiology details some theoretical shortcomings of that procedural model. An alternative approach employing high-speed, general purpose digital computers is then presented. It is argued that the measurement potential of computers is barely tapped by using computers to score sleep stages and the advantages of collecting data which are suitable for parametric and multivariate statistical analysis are described. Researchers are urged to include detailed reports on their procedural choices along with a discussion of the methodological implications of these procedures. Examples of computer collected data are presented along with a description of some simple data reduction strategies.", "contents": "Conceptual and methodological considerations towards the development of computer-controlled research on the electro-physiology of sleep. A critical discussion of the visual scoring approach to the measurement of sleep electrophysiology details some theoretical shortcomings of that procedural model. An alternative approach employing high-speed, general purpose digital computers is then presented. It is argued that the measurement potential of computers is barely tapped by using computers to score sleep stages and the advantages of collecting data which are suitable for parametric and multivariate statistical analysis are described. Researchers are urged to include detailed reports on their procedural choices along with a discussion of the methodological implications of these procedures. Examples of computer collected data are presented along with a description of some simple data reduction strategies."}
{"id": "PMID:227172", "title": "[Comparative study of the hemolytic action of group D vitamins].", "content": "Hemolytic effects of the vitamins of the D group (ergocalciferol - D2, cholecalciferol - D3, and 1 alpha-hydroxycholecalciferol - 1 alpha-OH-D3) were compared using rat erythrocytes. The latent period of hemolysis, caused by 1 alpha-OH-D3 was approximately 3-fold shorter as compared with the hemolysis caused by D2 or D3. Apparent values for energy of activation of hemolysis, estimated at 30-45 degrees, constituted for D2 - 23.2 kcal/mol, D3 - 25.3 kcal/mol, 1 alpha-OH-D3 - 13.1 kcal/mol. Despite the higher hemolytic activity, the rate of 1 alpha-ON-D3 autooxidation was distinctly lower than that of D3.", "contents": "[Comparative study of the hemolytic action of group D vitamins]. Hemolytic effects of the vitamins of the D group (ergocalciferol - D2, cholecalciferol - D3, and 1 alpha-hydroxycholecalciferol - 1 alpha-OH-D3) were compared using rat erythrocytes. The latent period of hemolysis, caused by 1 alpha-OH-D3 was approximately 3-fold shorter as compared with the hemolysis caused by D2 or D3. Apparent values for energy of activation of hemolysis, estimated at 30-45 degrees, constituted for D2 - 23.2 kcal/mol, D3 - 25.3 kcal/mol, 1 alpha-OH-D3 - 13.1 kcal/mol. Despite the higher hemolytic activity, the rate of 1 alpha-ON-D3 autooxidation was distinctly lower than that of D3."}
{"id": "PMID:227177", "title": "[Polygraphic study of nocturnal sleep in three degenerative diseases: ALS, oligo-ponto-cerebellar atrophy, and progressive supranuclear palsy].", "content": "A polygraphic study of nocturnal sleep was carried out on 12 patients suffering from amyotrophic lateral sclerosis (ALS), 6 patients suffering from olivio-ponto-cerebellare-atrophia (OPCA) and 9 patients suffering from the Steele-Richardson disease (SR). A disturbance of sleep--if it exists--always runs parallel with the course of the disease. No disturbances were registered in the group of patients suffering from ALS, in the OPCA group a specific disease of paradoxal sleep is observed. The sleep disturbances are more global in the group of patients suffering from the SR disease. A particular electrooculogram was taken from the patients from the awakening and from the paradoxal sleep. Respiratory difficulties were registered on certain patients of each of the three groups. These sleep disturbances, registered by the polygraph, were compared with those observed on patients presenting a cortical disease.", "contents": "[Polygraphic study of nocturnal sleep in three degenerative diseases: ALS, oligo-ponto-cerebellar atrophy, and progressive supranuclear palsy]. A polygraphic study of nocturnal sleep was carried out on 12 patients suffering from amyotrophic lateral sclerosis (ALS), 6 patients suffering from olivio-ponto-cerebellare-atrophia (OPCA) and 9 patients suffering from the Steele-Richardson disease (SR). A disturbance of sleep--if it exists--always runs parallel with the course of the disease. No disturbances were registered in the group of patients suffering from ALS, in the OPCA group a specific disease of paradoxal sleep is observed. The sleep disturbances are more global in the group of patients suffering from the SR disease. A particular electrooculogram was taken from the patients from the awakening and from the paradoxal sleep. Respiratory difficulties were registered on certain patients of each of the three groups. These sleep disturbances, registered by the polygraph, were compared with those observed on patients presenting a cortical disease."}
{"id": "PMID:227178", "title": "Polygraphic analysis of sleep in dystonia musculorum deformans.", "content": "The functional state of non-specific brain systems was studied in 27 patients with torsion dystonia through a complex of techniques, which included clinical, experimental psychological and electrophysiological examination of night sleep. Changes of involved nature have been identified in the various elements of non-specific systems in different clinical forms of the disease in its early and advanced stages, which allows to consider torsion dystonia as a functional organic psychomotor syndrome in the origination of which a great role belongs to non-specific integrative systems of the brain.", "contents": "Polygraphic analysis of sleep in dystonia musculorum deformans. The functional state of non-specific brain systems was studied in 27 patients with torsion dystonia through a complex of techniques, which included clinical, experimental psychological and electrophysiological examination of night sleep. Changes of involved nature have been identified in the various elements of non-specific systems in different clinical forms of the disease in its early and advanced stages, which allows to consider torsion dystonia as a functional organic psychomotor syndrome in the origination of which a great role belongs to non-specific integrative systems of the brain."}
{"id": "PMID:227179", "title": "Short-term effects of CHO, fat and protein loads on total tryptophan/tyrosine levels in plasma as related to %REM sleep.", "content": "The effect on plasma amino acid levels and sleep parameters of three experimental diet conditions was investigated in 12 healthy young men. A total of 71 sleep records and 715 plasma samples were analysed for %REM (TDT) and total plasma tryptophan and tyrosine respectively. The ratio of tryptophan to tyrosine was virtually the same under the fat supplement as under the nosupplement conditions. The ratio associated with the CHO load was found to be 14 per cent higher, however. A 29 per cent higher value found with the Protein load may be misleading due to the nature of the supplement used. %REM (TDT) was not found to be significantly related to any of the above conditions.", "contents": "Short-term effects of CHO, fat and protein loads on total tryptophan/tyrosine levels in plasma as related to %REM sleep. The effect on plasma amino acid levels and sleep parameters of three experimental diet conditions was investigated in 12 healthy young men. A total of 71 sleep records and 715 plasma samples were analysed for %REM (TDT) and total plasma tryptophan and tyrosine respectively. The ratio of tryptophan to tyrosine was virtually the same under the fat supplement as under the nosupplement conditions. The ratio associated with the CHO load was found to be 14 per cent higher, however. A 29 per cent higher value found with the Protein load may be misleading due to the nature of the supplement used. %REM (TDT) was not found to be significantly related to any of the above conditions."}
{"id": "PMID:227180", "title": "Effects of L-tryptophan on sleep onset insomniacs.", "content": "Eighteen female subjects with demonstrated laboratory sleep onset latency greater than 20 minutes for two nights participated in this double blind study of the effectiveness of l-tryptophan as a hypnotic. Standard sleep recordings were made on 10 nights over a 3 month period with lights out occurring 20 minutes after drug administration (placebo, 1 gm. l-tryptophan, 3 gms. l-tryptophan). Neither dose of l-tryptophan differed from placebo as to the amount of REM, SWS or wakefulness, but 3 gms. significantly reduced sleep onset latency on some of the nights. Those subjects with latencies longer than 40 mins. had the greatest reduction in latency with 3 gms. and also evidenced high levels of anxiety on the Taylor Manifest Anxiety Scale initially. Subjects with latency between 20 and 40 minutes appeared to receive the longest lasting hypnotic effect from the higher dose. Adaptation to the sleep lab took place across the entire 10 nights of the study. Therefore, valid comparisons between treatments in a sleep study extending over a number of nights should be made between temporally adjacent samples.", "contents": "Effects of L-tryptophan on sleep onset insomniacs. Eighteen female subjects with demonstrated laboratory sleep onset latency greater than 20 minutes for two nights participated in this double blind study of the effectiveness of l-tryptophan as a hypnotic. Standard sleep recordings were made on 10 nights over a 3 month period with lights out occurring 20 minutes after drug administration (placebo, 1 gm. l-tryptophan, 3 gms. l-tryptophan). Neither dose of l-tryptophan differed from placebo as to the amount of REM, SWS or wakefulness, but 3 gms. significantly reduced sleep onset latency on some of the nights. Those subjects with latencies longer than 40 mins. had the greatest reduction in latency with 3 gms. and also evidenced high levels of anxiety on the Taylor Manifest Anxiety Scale initially. Subjects with latency between 20 and 40 minutes appeared to receive the longest lasting hypnotic effect from the higher dose. Adaptation to the sleep lab took place across the entire 10 nights of the study. Therefore, valid comparisons between treatments in a sleep study extending over a number of nights should be made between temporally adjacent samples."}
{"id": "PMID:227183", "title": "[Tracheal and bronchial cylindromas (author's transl)].", "content": "Cylindromas, characterized by its invasive growth, contain 3.7% of all adenomas of bronchial tree (160). Two of 10 cases of tumours mestastized. However, unqualified cylindromas attaching to cancers (adenoid cystic cancer) is not justified. Histological structure of cylindromas is more variable than it is described by other authors. It is proposed to differ 4 histological variants: cribrouse, trabecular, and chondroid. Histological, histochemical and electronmicroscopical analysis allowed to discover the dual character of tumour cell secretion. As to its chemical composition, the secretion of the lumen of mucous tubulae resembles the ordinary mucus, but in cribrouse nests and across trabecular periphery and solid nests it was discovered the particular (special) secretion, rich in acid mucopolysaccharides. Feyrter's observation of endocrine activity of cylindromas are not confirmed. Tissue source of cylindromas of different localizations, in particular, bronchial may be myoepithelial cells.", "contents": "[Tracheal and bronchial cylindromas (author's transl)]. Cylindromas, characterized by its invasive growth, contain 3.7% of all adenomas of bronchial tree (160). Two of 10 cases of tumours mestastized. However, unqualified cylindromas attaching to cancers (adenoid cystic cancer) is not justified. Histological structure of cylindromas is more variable than it is described by other authors. It is proposed to differ 4 histological variants: cribrouse, trabecular, and chondroid. Histological, histochemical and electronmicroscopical analysis allowed to discover the dual character of tumour cell secretion. As to its chemical composition, the secretion of the lumen of mucous tubulae resembles the ordinary mucus, but in cribrouse nests and across trabecular periphery and solid nests it was discovered the particular (special) secretion, rich in acid mucopolysaccharides. Feyrter's observation of endocrine activity of cylindromas are not confirmed. Tissue source of cylindromas of different localizations, in particular, bronchial may be myoepithelial cells."}
{"id": "PMID:227185", "title": "[Spin-lattice-relaxationtime T1 measurements of nucleosides (author's transl)].", "content": "Nucleosides and nucleotides have been investigated by means of the spin-lattice-relaxationtime T1, the measurements carried out in CDCl3 on the nucleosides adenosine (A), uridine (U) and inosine (I) indicate that the strength of H-bonding is highest in the basepair (A)--(U). The systems (A)--(A), (U)--(U), (I)--(A) and (I)--(U) however, show only a low tendency to associate. Plotting the spin-lattice-relaxationtime, of the nucleotide protons in fragments (mol weight below 40,000) originated from DNA or RNA, against increasing temperature gives a curve with a sigmoide shape and a Tm value of 80 degrees C. The average of the activation energy for the H-bonding is 18.02 KJ/mol. The investigations clearly show that the spin-lattice-relaxationtime measurements open first of all a new method for research on H-bonding, secondly it is even in the case of nucleosides and oligonucleotides, where most of the common methods fail, a way to get information about H-bonding effects.", "contents": "[Spin-lattice-relaxationtime T1 measurements of nucleosides (author's transl)]. Nucleosides and nucleotides have been investigated by means of the spin-lattice-relaxationtime T1, the measurements carried out in CDCl3 on the nucleosides adenosine (A), uridine (U) and inosine (I) indicate that the strength of H-bonding is highest in the basepair (A)--(U). The systems (A)--(A), (U)--(U), (I)--(A) and (I)--(U) however, show only a low tendency to associate. Plotting the spin-lattice-relaxationtime, of the nucleotide protons in fragments (mol weight below 40,000) originated from DNA or RNA, against increasing temperature gives a curve with a sigmoide shape and a Tm value of 80 degrees C. The average of the activation energy for the H-bonding is 18.02 KJ/mol. The investigations clearly show that the spin-lattice-relaxationtime measurements open first of all a new method for research on H-bonding, secondly it is even in the case of nucleosides and oligonucleotides, where most of the common methods fail, a way to get information about H-bonding effects."}
{"id": "PMID:227186", "title": "On the possible involvement of ascorbic acid and copper proteins in leukemia. III. ESR investigations on the interaction between ascorbic acid and some transition metal ions.", "content": "The interaction between lyophilized samples of ascorbic acid and Cu2+, Fe3+ or Mn2+ has been investigated by means of ESR spectroscopy. All of the three transition metal ions form complexes with vitamin C, but only in the case of Cu2+ and Fe3+ the interaction results in a reduction of the metal ions. Cu2+ and ascorbic acid seem to form 2 : 1 complexes with an equilibrium constant of about K = 1 X 10(7) mol-1. None of these metal ion complexes exhibits, however, the ESR spectrum obtained with leukemic blood.", "contents": "On the possible involvement of ascorbic acid and copper proteins in leukemia. III. ESR investigations on the interaction between ascorbic acid and some transition metal ions. The interaction between lyophilized samples of ascorbic acid and Cu2+, Fe3+ or Mn2+ has been investigated by means of ESR spectroscopy. All of the three transition metal ions form complexes with vitamin C, but only in the case of Cu2+ and Fe3+ the interaction results in a reduction of the metal ions. Cu2+ and ascorbic acid seem to form 2 : 1 complexes with an equilibrium constant of about K = 1 X 10(7) mol-1. None of these metal ion complexes exhibits, however, the ESR spectrum obtained with leukemic blood."}
{"id": "PMID:227187", "title": "On the possible involvement of ascorbic acid and copper proteins in leukemia. IV. ESR investigations on the interaction between ascorbic acid and some copper proteins.", "content": "The interaction between lyophilized samples of ascorbic acid and some copper proteins (ceruloplasmin, cytochrome-c-oxidase, ascorbate-oxidase) has been investigated by means of ESR spectroscopy. The spectra obtained are identical to the one obtained with leukemic blood. The consequences of this for the molecular events occurring in cancer are discussed. The model proposed can explain the experimental findings reported thus far (such as change in spin concentration with the development of cancer, the presence of a high concentration of antioxidants etc.) as well as reconsile the two existing and seemingly contradictory hypothesis. Possible implications for lipid peroxidation and for the respiratory process are discussed.", "contents": "On the possible involvement of ascorbic acid and copper proteins in leukemia. IV. ESR investigations on the interaction between ascorbic acid and some copper proteins. The interaction between lyophilized samples of ascorbic acid and some copper proteins (ceruloplasmin, cytochrome-c-oxidase, ascorbate-oxidase) has been investigated by means of ESR spectroscopy. The spectra obtained are identical to the one obtained with leukemic blood. The consequences of this for the molecular events occurring in cancer are discussed. The model proposed can explain the experimental findings reported thus far (such as change in spin concentration with the development of cancer, the presence of a high concentration of antioxidants etc.) as well as reconsile the two existing and seemingly contradictory hypothesis. Possible implications for lipid peroxidation and for the respiratory process are discussed."}
{"id": "PMID:227188", "title": "[Identity of polystome larvae, parasites of Dicroglossus occipitalis tadpoles, on the Ivory Coast (author's transl)].", "content": "The morphological analysis of the haptorial hooklets of african Polystomatidae shows that many species of larvae parasitize the tadpoles of Dicroglossus occipitalis (G\u00fcnther). These multiple infestations are in contrast to the close parasitic specificity recognized by the adult Polystomes. This difference is explained by the behaviour of the host and the notion of supplying host is introduced.", "contents": "[Identity of polystome larvae, parasites of Dicroglossus occipitalis tadpoles, on the Ivory Coast (author's transl)]. The morphological analysis of the haptorial hooklets of african Polystomatidae shows that many species of larvae parasitize the tadpoles of Dicroglossus occipitalis (G\u00fcnther). These multiple infestations are in contrast to the close parasitic specificity recognized by the adult Polystomes. This difference is explained by the behaviour of the host and the notion of supplying host is introduced."}
{"id": "PMID:227195", "title": "[Correlations between HSV-2-infection and precancerous condition of uterine cervix (author's transl)].", "content": "Two groups of patients were examined and compared. One of them had been made up of 113 women from whom positive cytological responses had been recorded to colposcopy, and the other included 59 women with negative findings. The titres to HSV-2-infection were higher with significance in the first group. The authors conclusion is that HSV-2 infection might be one of the risk factors contributory to carcinogenesis in the uterine cervix.", "contents": "[Correlations between HSV-2-infection and precancerous condition of uterine cervix (author's transl)]. Two groups of patients were examined and compared. One of them had been made up of 113 women from whom positive cytological responses had been recorded to colposcopy, and the other included 59 women with negative findings. The titres to HSV-2-infection were higher with significance in the first group. The authors conclusion is that HSV-2 infection might be one of the risk factors contributory to carcinogenesis in the uterine cervix."}
{"id": "PMID:227196", "title": "[Cytotoxic antibodies in the serum of C3H mice after inoculating them with spontaneous mammary gland tumor cells].", "content": "Complement-dependent cytotoxic antibodies against the cells of mammary tumor MMTI appeared in the blood of C3H/He and C3Hf mice at the terminal stage of tumor growth; at the same time the mice of the above-mentioned substrains showed no difference in the degree of reaction. The level of natural cytotoxic antibodies against MMTI tumor cells detected in old C3H/He and C3Hf mice significantly exceeded their level in young mice affected with tumor; however, MMTI tumor cells grew equally fast in both old and young animals. The sera of mice affected with tumor had a weak cytolytic activity against the cells of hepatoma 22a and did not affect L cells and embryonal fibroblasts. The sera were partially exhasted by spleen and renal tissues, as well as the cells of spontaneous mammary tumor obtained from syngeneic animals and were not exhausted by allogenic cells infected with Rauscher murine leukemia virus.", "contents": "[Cytotoxic antibodies in the serum of C3H mice after inoculating them with spontaneous mammary gland tumor cells]. Complement-dependent cytotoxic antibodies against the cells of mammary tumor MMTI appeared in the blood of C3H/He and C3Hf mice at the terminal stage of tumor growth; at the same time the mice of the above-mentioned substrains showed no difference in the degree of reaction. The level of natural cytotoxic antibodies against MMTI tumor cells detected in old C3H/He and C3Hf mice significantly exceeded their level in young mice affected with tumor; however, MMTI tumor cells grew equally fast in both old and young animals. The sera of mice affected with tumor had a weak cytolytic activity against the cells of hepatoma 22a and did not affect L cells and embryonal fibroblasts. The sera were partially exhasted by spleen and renal tissues, as well as the cells of spontaneous mammary tumor obtained from syngeneic animals and were not exhausted by allogenic cells infected with Rauscher murine leukemia virus."}
{"id": "PMID:227193", "title": "[Inhibitory effect of hydrocortisone and corticotropin on the self stimulation reaction].", "content": "The effect of hydrocortisone and ACTG on the frequency of self-stimulation reaction (SS) was studied. It was shown that hydrocortisone markedly suppresses the central mechanism of the positive reinforcement. SS frequency is lowered 10-15 minutes after the drug administration and recovered in one hour. The changes in the frequency of SS in response to ACTG are simular to the hydrocortisone effect, but are less intensive and in some cases depend on the location of the stimulating electrodes.", "contents": "[Inhibitory effect of hydrocortisone and corticotropin on the self stimulation reaction]. The effect of hydrocortisone and ACTG on the frequency of self-stimulation reaction (SS) was studied. It was shown that hydrocortisone markedly suppresses the central mechanism of the positive reinforcement. SS frequency is lowered 10-15 minutes after the drug administration and recovered in one hour. The changes in the frequency of SS in response to ACTG are simular to the hydrocortisone effect, but are less intensive and in some cases depend on the location of the stimulating electrodes."}
{"id": "PMID:227197", "title": "[Clinical and biochemical heterogeneity of the Lesch-Nyhan syndrome].", "content": "The screening program directed towards a detection of patients with hereditary enzymopathy allowed to reveal 8 boys from 4-14 years with the Lesch-Nyhana syndrome. Among these children 4 were studied in detail clinically and biochemically. The study demonstrated that there were different degrees of mental retardation, autoagressive or agressive behaviour. The activity of erythrocyte hypoxanthinguanine phosphoribosyltransferase (HGPRT) in 2 cases was not changed, in 1-decreased and in 1--was absent. In 1 case of a decreased activity of hypoxanthinguanine phosphoribosyltransferase there was a drastic drop in the activity of adeninphosphoribosyltransferase (APRT). The study showed that there was a double increase in the cerruloplasmin activity in the blood plasma and of the cytochromoxydase in the leukocyte mitochondria. This indicates that the genetically determined drop in the HGPRT or APRT leads to disturbances in the other links of metabolism in the organism. The clinical manifestation of the disease due to a disturbed metabolism of biogen amines in the CNS is postulated.", "contents": "[Clinical and biochemical heterogeneity of the Lesch-Nyhan syndrome]. The screening program directed towards a detection of patients with hereditary enzymopathy allowed to reveal 8 boys from 4-14 years with the Lesch-Nyhana syndrome. Among these children 4 were studied in detail clinically and biochemically. The study demonstrated that there were different degrees of mental retardation, autoagressive or agressive behaviour. The activity of erythrocyte hypoxanthinguanine phosphoribosyltransferase (HGPRT) in 2 cases was not changed, in 1-decreased and in 1--was absent. In 1 case of a decreased activity of hypoxanthinguanine phosphoribosyltransferase there was a drastic drop in the activity of adeninphosphoribosyltransferase (APRT). The study showed that there was a double increase in the cerruloplasmin activity in the blood plasma and of the cytochromoxydase in the leukocyte mitochondria. This indicates that the genetically determined drop in the HGPRT or APRT leads to disturbances in the other links of metabolism in the organism. The clinical manifestation of the disease due to a disturbed metabolism of biogen amines in the CNS is postulated."}
{"id": "PMID:227198", "title": "Protein-cationic detergent interaction. Interaction of bovine serum albumin and other proteins with alkylpyridinium bromides studied by viscosity, gel filtration and spin-label methods.", "content": "Viscosity, gel filtration and spin-labelling methods have been used to study the influence of alkylpyridinium bromides on the conformation of bovine serum albumin and other proteins. Cationic detergents cause partial unfolding of the native protein molecules. The magnitude of these changes increases with increasing length of the detergent hydrocarbon chain. When cationic detergents are added to reduced and carboxymethylated bovine serum albumin the observed changes are opposite to those found in native protein.", "contents": "Protein-cationic detergent interaction. Interaction of bovine serum albumin and other proteins with alkylpyridinium bromides studied by viscosity, gel filtration and spin-label methods. Viscosity, gel filtration and spin-labelling methods have been used to study the influence of alkylpyridinium bromides on the conformation of bovine serum albumin and other proteins. Cationic detergents cause partial unfolding of the native protein molecules. The magnitude of these changes increases with increasing length of the detergent hydrocarbon chain. When cationic detergents are added to reduced and carboxymethylated bovine serum albumin the observed changes are opposite to those found in native protein."}
{"id": "PMID:227199", "title": "Metal--glutathione interaction in aqueous solution. Nickel(II), cobalt(II) and copper(II) complexes with oxidized glutathione.", "content": "The interaction of copper(II), nickel(II) and cobalt(II) ions with oxidized glutathione in aqueous solutions have been examined by spectroscopic methods. Cu(II) is the only ion which interacts with disulphide bridge and forms dimeric species containing the Cu(II)-S-S-Cu(II) unit. Ni(II) and Co(II) bind mainly with the terminal NH2 and COO- groups of glutamic acid, and the complexes formed are of nearly octahedral symmetry. At high pH, in the Co(II)-GSSG solution Co(II) is oxidized to Co(III) with the concomitant reduction of GSSG to GSH. Considerable differences were observed between the oxidized and reduced form of glutathione in the coordination ability towards metal ions.", "contents": "Metal--glutathione interaction in aqueous solution. Nickel(II), cobalt(II) and copper(II) complexes with oxidized glutathione. The interaction of copper(II), nickel(II) and cobalt(II) ions with oxidized glutathione in aqueous solutions have been examined by spectroscopic methods. Cu(II) is the only ion which interacts with disulphide bridge and forms dimeric species containing the Cu(II)-S-S-Cu(II) unit. Ni(II) and Co(II) bind mainly with the terminal NH2 and COO- groups of glutamic acid, and the complexes formed are of nearly octahedral symmetry. At high pH, in the Co(II)-GSSG solution Co(II) is oxidized to Co(III) with the concomitant reduction of GSSG to GSH. Considerable differences were observed between the oxidized and reduced form of glutathione in the coordination ability towards metal ions."}
{"id": "PMID:227200", "title": "Nucleic acid and sulphated glycosaminoglycan synthesis in the peritoneal membrane and in intra-abdominal adhesions in rat as affected by silica-induced peritonitis.", "content": "The synthesis of DNA, RNA and glycosaminoglycans was studied in the peritoneal membrane and intra-abdominal adhesions formed in rats after a single colloidal silica injection. The concentration of DNA and RNA increased from the first day of peritonitis reaching the maximum at 4--7 days in both the peritoneum and adhesions. On the other hand the synthesis of radioactive DNA and RNA from 3H-thymidine and 3H-cytidine increased during the first 12 hours and was maximal at 24 hours in the peritoneum and at 48 hours in the adhesions. Although the contents of uronic acids were maximal at 24 hours in the peritoneum and at 2--4 days in the adhesions, the maximal synthesis rate of sulphated glycosaminoglycans was observed at 5 days in the peritoneum and at 7 days in the adhesions. The difference in the uronic acid concentration and radioactivities of glycosaminoglycans was probably due to increased permeability of the peritoneal membrane and exudation. Earlier we observed that protein synthesis was maximal at 7 days and that of collagen at 3 weeks. On the basis of these and the present results it is obvious that the order of synthesis of these connective tissue components in the peritoneum after chemical peritonitis follows the pattern of tissue reaction in wound healing and in experimental subcutaneous granuloma formation. However, the activation of nucleic acid and glycosaminoglycan synthesis occurs promptly without any or with a very short lag period in the peritoneal mesenchymal tissue.", "contents": "Nucleic acid and sulphated glycosaminoglycan synthesis in the peritoneal membrane and in intra-abdominal adhesions in rat as affected by silica-induced peritonitis. The synthesis of DNA, RNA and glycosaminoglycans was studied in the peritoneal membrane and intra-abdominal adhesions formed in rats after a single colloidal silica injection. The concentration of DNA and RNA increased from the first day of peritonitis reaching the maximum at 4--7 days in both the peritoneum and adhesions. On the other hand the synthesis of radioactive DNA and RNA from 3H-thymidine and 3H-cytidine increased during the first 12 hours and was maximal at 24 hours in the peritoneum and at 48 hours in the adhesions. Although the contents of uronic acids were maximal at 24 hours in the peritoneum and at 2--4 days in the adhesions, the maximal synthesis rate of sulphated glycosaminoglycans was observed at 5 days in the peritoneum and at 7 days in the adhesions. The difference in the uronic acid concentration and radioactivities of glycosaminoglycans was probably due to increased permeability of the peritoneal membrane and exudation. Earlier we observed that protein synthesis was maximal at 7 days and that of collagen at 3 weeks. On the basis of these and the present results it is obvious that the order of synthesis of these connective tissue components in the peritoneum after chemical peritonitis follows the pattern of tissue reaction in wound healing and in experimental subcutaneous granuloma formation. However, the activation of nucleic acid and glycosaminoglycan synthesis occurs promptly without any or with a very short lag period in the peritoneal mesenchymal tissue."}
{"id": "PMID:227201", "title": "Malignant atrophic papulosis--Degos' syndrome.", "content": "A typical case of malignant atrophic papulosis is presented. The patient had had a symptomless, pathognomonic skin rash for 6 months and thereafter also multiple intestinal infarctions which caused perforations, peritonitis, and finally death. All therapeutic attempts, including intestinal resection and acetylsalicylic acid combined with dipyridamole, were in vain. Electron microscopy showed 200-250 A large virus-like cytoplasmic inclusions in the endothelial cells, without degenerative or regenerative changes, in a quite fresh papule. It was not possible to culture viruses on skin fibroblasts, but further studies of these inclusions are needed.", "contents": "Malignant atrophic papulosis--Degos' syndrome. A typical case of malignant atrophic papulosis is presented. The patient had had a symptomless, pathognomonic skin rash for 6 months and thereafter also multiple intestinal infarctions which caused perforations, peritonitis, and finally death. All therapeutic attempts, including intestinal resection and acetylsalicylic acid combined with dipyridamole, were in vain. Electron microscopy showed 200-250 A large virus-like cytoplasmic inclusions in the endothelial cells, without degenerative or regenerative changes, in a quite fresh papule. It was not possible to culture viruses on skin fibroblasts, but further studies of these inclusions are needed."}
{"id": "PMID:227202", "title": "Restoration of oestrogen positive feedback effect on LH release by bromocriptine in hyperprolactinaemic patients with galactorrhoea-amenorrhoea.", "content": "Five mg of bromocriptine was administered for 3 weeks to 8 hyperprolactinaemic women with galactorrhoea-amernorrhoea, in whom the response of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to 100 micrograms of iv LH-releasing hormone (LH-RH) had been evaluated. Twenty mg of conjugated oestrogen (Premarin) was injected iv any day between the 10th and 12th day from the initiation of the treatment, and serum LH levels were serially determined for 120 h. Hyperresponse of LH with normal FSH response to LH-RH was observed in most patients. Bromocriptine treatment for 10 to 12 days significantly suppressed mean (+/- SE) serum prolactin (PRL) levels from 65.1 +/- 23.0 to 10.4 +/- 2.0 ng/ml, while LH (12.6 +/- 2.1 to 24.8 +/- 5.9 mIU/ml) and oestradiol (40.1 +/- 7.6 to 111.4 +/- 20.8 pg/ml) levels increased significantly. Patients on bromocriptine treatment showed LH release with a peak at 48 h after injection of Premarin. The mean per cent increases in LH were significantly higher than those in untreated patients with galactorrhoea-amenorrhoea between 32 and 96 h after the injection. The present results seem to suggest that the restoration of LH-releasing response to oestrogen following suppression of PRL by bromocriptine may play an important role in induction of ovulation in hyperprolactinaemic patients with galactorrhoea-amenorrhoea.", "contents": "Restoration of oestrogen positive feedback effect on LH release by bromocriptine in hyperprolactinaemic patients with galactorrhoea-amenorrhoea. Five mg of bromocriptine was administered for 3 weeks to 8 hyperprolactinaemic women with galactorrhoea-amernorrhoea, in whom the response of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to 100 micrograms of iv LH-releasing hormone (LH-RH) had been evaluated. Twenty mg of conjugated oestrogen (Premarin) was injected iv any day between the 10th and 12th day from the initiation of the treatment, and serum LH levels were serially determined for 120 h. Hyperresponse of LH with normal FSH response to LH-RH was observed in most patients. Bromocriptine treatment for 10 to 12 days significantly suppressed mean (+/- SE) serum prolactin (PRL) levels from 65.1 +/- 23.0 to 10.4 +/- 2.0 ng/ml, while LH (12.6 +/- 2.1 to 24.8 +/- 5.9 mIU/ml) and oestradiol (40.1 +/- 7.6 to 111.4 +/- 20.8 pg/ml) levels increased significantly. Patients on bromocriptine treatment showed LH release with a peak at 48 h after injection of Premarin. The mean per cent increases in LH were significantly higher than those in untreated patients with galactorrhoea-amenorrhoea between 32 and 96 h after the injection. The present results seem to suggest that the restoration of LH-releasing response to oestrogen following suppression of PRL by bromocriptine may play an important role in induction of ovulation in hyperprolactinaemic patients with galactorrhoea-amenorrhoea."}
{"id": "PMID:227203", "title": "Corticosterone secreting adrenal carcinoma and empty sella turcica: a case report.", "content": "Pituitary adenoma was suspected in a woman of 74 with hypercorticism,hypokalaemic alkalosis and radiographically enlarged sella turcica. However, non-suppressibility of steroid excretion by high-dose dexamethasone and low plasma concentration of ACTH suggested adrenal tumour. Detailed analysis of urinary steroid excretions demonstrated unusually large amounts of corticosterone metabolites, 14.6 mg/24 h compared to a mean normal value of 0.5 mg. The basal levels of the remaining pituitary hormones were unremarkable. The patient died incidentally before a planned adrenalectomy. The autopsy disclosed an adrenal carcinoma and an empty sella turcica. The enlarged pituitary fossa was lined by a narrow rim of histological normal pituitary tissue.", "contents": "Corticosterone secreting adrenal carcinoma and empty sella turcica: a case report. Pituitary adenoma was suspected in a woman of 74 with hypercorticism,hypokalaemic alkalosis and radiographically enlarged sella turcica. However, non-suppressibility of steroid excretion by high-dose dexamethasone and low plasma concentration of ACTH suggested adrenal tumour. Detailed analysis of urinary steroid excretions demonstrated unusually large amounts of corticosterone metabolites, 14.6 mg/24 h compared to a mean normal value of 0.5 mg. The basal levels of the remaining pituitary hormones were unremarkable. The patient died incidentally before a planned adrenalectomy. The autopsy disclosed an adrenal carcinoma and an empty sella turcica. The enlarged pituitary fossa was lined by a narrow rim of histological normal pituitary tissue."}
{"id": "PMID:227204", "title": "Angiotensin II and K challenge following prolonged ACTH administration to normal subjects.", "content": "Twelve healthy male volunteers on a normal Na and K intake and ambulatory received ACTH (40 IU, im) twice daily for 5 days followed by 2 days of angiotensin II (5--13 ng/kg body weight/min for 60 min) or oral K citrate (30 mEq./h x 3). A discordance in the aldosterone-stimulating and pressor responses of angiotensin II was unmasked with only the latter response being positive following ACTH-induced refractoriness. K loading was a much more potent natriuretic stimulus than angiotensin II treatment. In contrast to angiotensin II, K could selectively enhance aldosterone secretion by overcoming the inhibition in secretion of the mineralocorticoid induced by prolonged ACTH exposure.", "contents": "Angiotensin II and K challenge following prolonged ACTH administration to normal subjects. Twelve healthy male volunteers on a normal Na and K intake and ambulatory received ACTH (40 IU, im) twice daily for 5 days followed by 2 days of angiotensin II (5--13 ng/kg body weight/min for 60 min) or oral K citrate (30 mEq./h x 3). A discordance in the aldosterone-stimulating and pressor responses of angiotensin II was unmasked with only the latter response being positive following ACTH-induced refractoriness. K loading was a much more potent natriuretic stimulus than angiotensin II treatment. In contrast to angiotensin II, K could selectively enhance aldosterone secretion by overcoming the inhibition in secretion of the mineralocorticoid induced by prolonged ACTH exposure."}
{"id": "PMID:227205", "title": "Effect of two prostaglandin synthesis inhibitors, indomethacin and acetylsalicylic acid, on plasma ACTH and cortisol levels in man.", "content": "The aim of this study was to investigate the possible role of prostaglandins (PG) in the control of the hypohtalamic-pituitary-adrenocortical axis in normal volunteers. Acute oral administration of 100 mg indomethacin (ID) or 1.5 g acetylsalicylic acid (ASA) did not alter ACTH and cortisol plasma levels. Administration of 300 mg daily ID for 4 days delayed the onset, but increased the magnitude, of the response of ACTH to insulin hypoglycaemia, while it blunted the cortisol response. Administration of 3.2 g ASA daily depressed ACTH response to hypoglycaemia leaving the cortisol response unchanged, except for a 15 min delay in onset. These results are interpreted assuming that ID and ASA chiefly acted at the pituitary and hypothalamic level, respectively, and that ID, but not ASA, interfered with adrenocortical cortisol production. Our findings support the concept, based on animal studies, that PG enhance hypothalamic CRF release and adrenocortical steroidogenesis and may restrain ACTH secretion in the pituitary.", "contents": "Effect of two prostaglandin synthesis inhibitors, indomethacin and acetylsalicylic acid, on plasma ACTH and cortisol levels in man. The aim of this study was to investigate the possible role of prostaglandins (PG) in the control of the hypohtalamic-pituitary-adrenocortical axis in normal volunteers. Acute oral administration of 100 mg indomethacin (ID) or 1.5 g acetylsalicylic acid (ASA) did not alter ACTH and cortisol plasma levels. Administration of 300 mg daily ID for 4 days delayed the onset, but increased the magnitude, of the response of ACTH to insulin hypoglycaemia, while it blunted the cortisol response. Administration of 3.2 g ASA daily depressed ACTH response to hypoglycaemia leaving the cortisol response unchanged, except for a 15 min delay in onset. These results are interpreted assuming that ID and ASA chiefly acted at the pituitary and hypothalamic level, respectively, and that ID, but not ASA, interfered with adrenocortical cortisol production. Our findings support the concept, based on animal studies, that PG enhance hypothalamic CRF release and adrenocortical steroidogenesis and may restrain ACTH secretion in the pituitary."}
{"id": "PMID:227206", "title": "Inhibitory effect of dibutyryl cyclic AMP on the release of calcium, inorganic phosphate and lysosomal enzymes from calvarial bones cultured for 24 hours.", "content": "The effect of N6,O2'-dibutyryl adenosine 3',5'-cyclic-monophosphate (dbcAMP) on the mobilization of calcium (Ca2+), inorganic phosphate (Pi) and lysosomal enzymes was studied in a bone culture system for 24 h using half calvaria from 6--7 day-old mice. DbcAMP inhibited spontaneous as well as parathyroid hormone-stimulated mineral mobilization. DbcAMP in a concentration of 5 x 10(-4)M also reduced the activities of beta-glucuronidase, beta-galactosidase and acid phosphatase found in the media while the activities of lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase were not affected. It is concluded that cAMP is not a stimulator but an inhibitor of bone resorption within the culture period studied (24 h) and that the cyclic nucleotide might interfere with release processes involved in bone resorption.", "contents": "Inhibitory effect of dibutyryl cyclic AMP on the release of calcium, inorganic phosphate and lysosomal enzymes from calvarial bones cultured for 24 hours. The effect of N6,O2'-dibutyryl adenosine 3',5'-cyclic-monophosphate (dbcAMP) on the mobilization of calcium (Ca2+), inorganic phosphate (Pi) and lysosomal enzymes was studied in a bone culture system for 24 h using half calvaria from 6--7 day-old mice. DbcAMP inhibited spontaneous as well as parathyroid hormone-stimulated mineral mobilization. DbcAMP in a concentration of 5 x 10(-4)M also reduced the activities of beta-glucuronidase, beta-galactosidase and acid phosphatase found in the media while the activities of lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase were not affected. It is concluded that cAMP is not a stimulator but an inhibitor of bone resorption within the culture period studied (24 h) and that the cyclic nucleotide might interfere with release processes involved in bone resorption."}
{"id": "PMID:227207", "title": "Urinary excretion of calcium, hydroxyproline and 3',5'-cyclic adenosine monophosphate in primary hyperparathyroidism.", "content": "Urinary excretion of calcium (Ca), hydroxyproline (Hyp) and 3',5'-cyclic adenosine monophosphate (cAMP) was measured during fasting, and in the afternoon, over a 3 day period. Twelve hyperparathyroid patients, of whom 6 were re-studied after successful parathyroid surgery, and 10 control subjects participated, and were maintained on a collagen free diet for the duration of the study. Expressed as creatinine ratio values, Hyp was significantly higher in the morning than during the afternoon, whereas the Ca excretion pattern showed low morning and high afternoon values for all groups. cAMP excretion did not change during the two sampling periods. Large day to day variations for each parameter were observed in the individual patient. The value of cAMP measurements in the diagnosis of primary hyperparathyroidism was confirmed. The results may imply that a diurnal variation in Hyp excretion exists in primary hyperparathyroidism and that food intake produces a suppression of Hyp excretion, possibly secondary to suppression of parathyroid function or, in our view, to increased calcitonin excretion.", "contents": "Urinary excretion of calcium, hydroxyproline and 3',5'-cyclic adenosine monophosphate in primary hyperparathyroidism. Urinary excretion of calcium (Ca), hydroxyproline (Hyp) and 3',5'-cyclic adenosine monophosphate (cAMP) was measured during fasting, and in the afternoon, over a 3 day period. Twelve hyperparathyroid patients, of whom 6 were re-studied after successful parathyroid surgery, and 10 control subjects participated, and were maintained on a collagen free diet for the duration of the study. Expressed as creatinine ratio values, Hyp was significantly higher in the morning than during the afternoon, whereas the Ca excretion pattern showed low morning and high afternoon values for all groups. cAMP excretion did not change during the two sampling periods. Large day to day variations for each parameter were observed in the individual patient. The value of cAMP measurements in the diagnosis of primary hyperparathyroidism was confirmed. The results may imply that a diurnal variation in Hyp excretion exists in primary hyperparathyroidism and that food intake produces a suppression of Hyp excretion, possibly secondary to suppression of parathyroid function or, in our view, to increased calcitonin excretion."}
{"id": "PMID:227208", "title": "Imparied cyclic-AMP response to thyrotrophin in congenital hypothyroidism with thyroglobulin deficiency.", "content": "A 19 year old man had congenital hypothyroidism and severely retarded development. His thyroid gland was not enlarged and laboratory findings included low serum concentration of T4 (2.8 microgram/100 ml) and T3 (16 ng/100 ml) with a high level of TSH (52 microU/ml) that rose to 192 microU/ml after TRH. 131I uptake by the thyroid was normal (41.5% at 24 h) and did not show a normal increase after exogenous TSH administration (49.5% at 24 h). The perchlorate discharge test was negative and no antibodies against thyroid antigens were found. Studies on the biopsy specimen revealed low iodide trapping by the thyroid slices and no formation of cyclic AMP after TSH was added to the medium. The endogenous TSH of the patient was biologically active increasing cyclic adenosine monophosphate c-AMP concentration in normal thyroid slices. No thyroglobulin was found in the thyroid tissue either by immunological or ultracentrifugational methods. An increased proportion of iodoalbumin was present in the serum. We postulate that the fundamental defect in this gland is an impaired generation of c-AMP by the defective thyroid cell and deficiency of thyroglobulin formation resulting in inadequate thyroxine and triiodothyronine synthesis.", "contents": "Imparied cyclic-AMP response to thyrotrophin in congenital hypothyroidism with thyroglobulin deficiency. A 19 year old man had congenital hypothyroidism and severely retarded development. His thyroid gland was not enlarged and laboratory findings included low serum concentration of T4 (2.8 microgram/100 ml) and T3 (16 ng/100 ml) with a high level of TSH (52 microU/ml) that rose to 192 microU/ml after TRH. 131I uptake by the thyroid was normal (41.5% at 24 h) and did not show a normal increase after exogenous TSH administration (49.5% at 24 h). The perchlorate discharge test was negative and no antibodies against thyroid antigens were found. Studies on the biopsy specimen revealed low iodide trapping by the thyroid slices and no formation of cyclic AMP after TSH was added to the medium. The endogenous TSH of the patient was biologically active increasing cyclic adenosine monophosphate c-AMP concentration in normal thyroid slices. No thyroglobulin was found in the thyroid tissue either by immunological or ultracentrifugational methods. An increased proportion of iodoalbumin was present in the serum. We postulate that the fundamental defect in this gland is an impaired generation of c-AMP by the defective thyroid cell and deficiency of thyroglobulin formation resulting in inadequate thyroxine and triiodothyronine synthesis."}
{"id": "PMID:227209", "title": "Adenyl cyclase activity in human thyroid plasma membranes from normal human thyroid tissue and thyroid adenomas.", "content": "The adenylcyclase (AC) activity of crude human thyroid plasma membranes were studied in some detail and conditions for optimal cyclic AMP-production established. Membranes from eight \"cold\" and two \"hot\" thyroid adenomas were investigated and compared to membranes from corresponding normal, paranodular tissues. The investigated membranes were found to contain similar basal AC activities, which were stimulated three to five times with TSH and 20--30 times with fluoride. Further, no difference in the TSH-sensitivity of AC from normal and \"cold\" adenomas could be detected. Thyrotrophin 0.02 mU/ml caused a measurable and 0.15 mU/ml a half-maximal stimulation of the cAMP-production. The data indicate, that disturbances of thyroid hormone production characteristic of thyroid adenomas, are not caused by alterations of the TSH-AC system and suggest that in a thyroid cell the degree of thyroid hormone synthesis do not alter the amount of plasma membrane-bound adenylcyclase.", "contents": "Adenyl cyclase activity in human thyroid plasma membranes from normal human thyroid tissue and thyroid adenomas. The adenylcyclase (AC) activity of crude human thyroid plasma membranes were studied in some detail and conditions for optimal cyclic AMP-production established. Membranes from eight \"cold\" and two \"hot\" thyroid adenomas were investigated and compared to membranes from corresponding normal, paranodular tissues. The investigated membranes were found to contain similar basal AC activities, which were stimulated three to five times with TSH and 20--30 times with fluoride. Further, no difference in the TSH-sensitivity of AC from normal and \"cold\" adenomas could be detected. Thyrotrophin 0.02 mU/ml caused a measurable and 0.15 mU/ml a half-maximal stimulation of the cAMP-production. The data indicate, that disturbances of thyroid hormone production characteristic of thyroid adenomas, are not caused by alterations of the TSH-AC system and suggest that in a thyroid cell the degree of thyroid hormone synthesis do not alter the amount of plasma membrane-bound adenylcyclase."}
{"id": "PMID:227210", "title": "Interaction of [125I]LH-RH and other oligopeptides with plasma membranes of rat anterior pituitaries.", "content": "The specific binding of [125I]LH-RH to isolated plasma membranes of rat pituitaries was investigated. The binding process was found to be highly specific, temperature-dependent and saturable. The dissociation constant as caluclated by three different methods was approximately 1.3 . 10(-8) M, indicating a single type of binding sites. Maximal binding capacity was 1 . 10(-12 moles/mg protein (= 2 ng LH-RH/pituitary gland), and the number of binding sites was calculated to be 6 . 10(11) per mg membrane protein (=1 . 10(10) binding sites/pituitary gland). When diluted with ice-cold buffer the dissociation of specifically bound LH-RH occurred very rapidly (half-life 3.17 min) with a rate constant of 0.219 min-1. The dissociation process followed first-order kinetics. Specificity of binding was demonstrated by dose-dependent competition of unlabelled LH-RH, the highly potent analogue D-glutamine-(cyclohexyl)6-LH-RH-nonapeptide-ethylamide and the fragment of an analogue (6-D-Ser(TBu))-LH-RH-(3-9)-heptapeptide-ethylamide with the binding [125I]LH-RH, while angiotensin I, II, oxytocin and bacitracin did not compete. The affinities of LH-RH and the analogue to the binding sites of the pituitary plasma membranes were not consistent with the respective biological activities.", "contents": "Interaction of [125I]LH-RH and other oligopeptides with plasma membranes of rat anterior pituitaries. The specific binding of [125I]LH-RH to isolated plasma membranes of rat pituitaries was investigated. The binding process was found to be highly specific, temperature-dependent and saturable. The dissociation constant as caluclated by three different methods was approximately 1.3 . 10(-8) M, indicating a single type of binding sites. Maximal binding capacity was 1 . 10(-12 moles/mg protein (= 2 ng LH-RH/pituitary gland), and the number of binding sites was calculated to be 6 . 10(11) per mg membrane protein (=1 . 10(10) binding sites/pituitary gland). When diluted with ice-cold buffer the dissociation of specifically bound LH-RH occurred very rapidly (half-life 3.17 min) with a rate constant of 0.219 min-1. The dissociation process followed first-order kinetics. Specificity of binding was demonstrated by dose-dependent competition of unlabelled LH-RH, the highly potent analogue D-glutamine-(cyclohexyl)6-LH-RH-nonapeptide-ethylamide and the fragment of an analogue (6-D-Ser(TBu))-LH-RH-(3-9)-heptapeptide-ethylamide with the binding [125I]LH-RH, while angiotensin I, II, oxytocin and bacitracin did not compete. The affinities of LH-RH and the analogue to the binding sites of the pituitary plasma membranes were not consistent with the respective biological activities."}
{"id": "PMID:227212", "title": "Further studies on hypothalamic-pituitary-testicular function in old rats.", "content": "The dysfunction of the hypothalamic-pituitary-gonadal axis in old age was studied in 24-month old male Wistar rats which were compared with 3-month old animals. The hypothalamic LH-RH content and the pituitary LH were significantly lower in the old than in the young adult animals. The plasma concentrations of LH and testosterone were significantly higher in the young rats. The primary cause of these age-dependent changes probably is a hypothalamic dysfunction. When isolated Leydig cells of young and old rats were incubated in vitro, the testosterone secretion per cell was significantly smaller in old than in young cells with as well as without HCG stimulation. In vivo stimulation of rats by iv injection of biologically active iodinated hCG revealed that the intratesticular uptake of the gonadotrophin was not different in young and old rats. The testosterone response, however, was significantly reduced in old age. An in vitro \"desensitisation\" experiment in which the LH receptor capacity was artificially reduced demonstrated that the 40% reduction of receptor capacity in old testes as described earlier will not impair the testicular uptake of gonadotrophin from blood. Repeated injection of hCG results in equally elevated testosterone concentrations in young and old rats.", "contents": "Further studies on hypothalamic-pituitary-testicular function in old rats. The dysfunction of the hypothalamic-pituitary-gonadal axis in old age was studied in 24-month old male Wistar rats which were compared with 3-month old animals. The hypothalamic LH-RH content and the pituitary LH were significantly lower in the old than in the young adult animals. The plasma concentrations of LH and testosterone were significantly higher in the young rats. The primary cause of these age-dependent changes probably is a hypothalamic dysfunction. When isolated Leydig cells of young and old rats were incubated in vitro, the testosterone secretion per cell was significantly smaller in old than in young cells with as well as without HCG stimulation. In vivo stimulation of rats by iv injection of biologically active iodinated hCG revealed that the intratesticular uptake of the gonadotrophin was not different in young and old rats. The testosterone response, however, was significantly reduced in old age. An in vitro \"desensitisation\" experiment in which the LH receptor capacity was artificially reduced demonstrated that the 40% reduction of receptor capacity in old testes as described earlier will not impair the testicular uptake of gonadotrophin from blood. Repeated injection of hCG results in equally elevated testosterone concentrations in young and old rats."}
{"id": "PMID:227217", "title": "[Phenoloxidase and peroxidase activity in presens of different effectors (author's transl)].", "content": "Small gut of the white rat was sectioned by the cryostat in slides of 10 microns and following effectors were investigated: KCN, sodium-diethyl-dithiocarbamate (DDC), NaF, sodium acetate, sodium pyruvate, 0.1 N HCl, 0.1 N NaOH, NaN3, and copper sulfate. Phenoloxidase is completely inhibited by DDC and HCl, incompletely by pyruvate and NaN3. Peroxidase also is completely inactivated by HCl and incompletely by NaN3. DDC has no effect on peroxidase, because a precipitate is formed. Neither of both enzyme activities is inhibited by KCN. In presence of KCN and copper sulfate an unspezific colouring of the tissue resulted in the phenoloxidase proof. Non of the investigated effectors is suitable to differentiate between phenoloxidase and peroxidase in histochemical investigations.", "contents": "[Phenoloxidase and peroxidase activity in presens of different effectors (author's transl)]. Small gut of the white rat was sectioned by the cryostat in slides of 10 microns and following effectors were investigated: KCN, sodium-diethyl-dithiocarbamate (DDC), NaF, sodium acetate, sodium pyruvate, 0.1 N HCl, 0.1 N NaOH, NaN3, and copper sulfate. Phenoloxidase is completely inhibited by DDC and HCl, incompletely by pyruvate and NaN3. Peroxidase also is completely inactivated by HCl and incompletely by NaN3. DDC has no effect on peroxidase, because a precipitate is formed. Neither of both enzyme activities is inhibited by KCN. In presence of KCN and copper sulfate an unspezific colouring of the tissue resulted in the phenoloxidase proof. Non of the investigated effectors is suitable to differentiate between phenoloxidase and peroxidase in histochemical investigations."}
{"id": "PMID:227218", "title": "Abnormal fat metabolism in chronic renal failure.", "content": "The serum triglyceride and cholesterol levels, the cholesterol and triglyceride concentrations in the lipoprotein fractions, as also postheparin lipoprotein-lipase activity (PHLA) were determined in 18 haemodialysis-patients with chronic renal failure. Hypertriglyceridaemia and hypocholesterolaemia were found together with increased VLDL- and LDL + HDL-triglyceride and decreased HDL-cholesterol concentrations. At 10 min after administration of heparin, enzyme activity was normal, at 20 min it was abnormally decreased.", "contents": "Abnormal fat metabolism in chronic renal failure. The serum triglyceride and cholesterol levels, the cholesterol and triglyceride concentrations in the lipoprotein fractions, as also postheparin lipoprotein-lipase activity (PHLA) were determined in 18 haemodialysis-patients with chronic renal failure. Hypertriglyceridaemia and hypocholesterolaemia were found together with increased VLDL- and LDL + HDL-triglyceride and decreased HDL-cholesterol concentrations. At 10 min after administration of heparin, enzyme activity was normal, at 20 min it was abnormally decreased."}
{"id": "PMID:227219", "title": "[Angiotensin converting enzyem (ACE) - a blood chemistry parameter in the diagnosis of sarcoidosis].", "content": "Serum angiotensin converting enzyme (ACE) activity was studied in 50 patients with sarcoidosis (39 active, 11 inactive sarcoidosis), as well as in 50 control patients (34 chronic lung diseases, 9 Hodgkin-disease, 7 rheumatoid arthritis). There is a significant difference (p less than 0.001) of ACE-activity between sarcoidosis patients and controls, and between active (without steroid treatment) and inactive sarcoidosis. Steroid treatment apparently lowers ACE-activity in sarcoidosis, however, without evidence for clinical improvement. Increased ACE-activity was also found in a patient with primary biliary cirrhosis.", "contents": "[Angiotensin converting enzyem (ACE) - a blood chemistry parameter in the diagnosis of sarcoidosis]. Serum angiotensin converting enzyme (ACE) activity was studied in 50 patients with sarcoidosis (39 active, 11 inactive sarcoidosis), as well as in 50 control patients (34 chronic lung diseases, 9 Hodgkin-disease, 7 rheumatoid arthritis). There is a significant difference (p less than 0.001) of ACE-activity between sarcoidosis patients and controls, and between active (without steroid treatment) and inactive sarcoidosis. Steroid treatment apparently lowers ACE-activity in sarcoidosis, however, without evidence for clinical improvement. Increased ACE-activity was also found in a patient with primary biliary cirrhosis."}
{"id": "PMID:227221", "title": "Plasma HDL cholesterol in epileptics with elevated triglyceride and cholesterol.", "content": "Due to the metabolic changes induced, e.g. in the liver by anti-epileptic drugs, the significance of high serum triglyceride and cholesterol in epileptics was studied and the plasma HDL cholesterol level was compared in 190 epileptic patients with elevated or normal triglyceride and cholesterol, with the corresponding values in 43 healthy subjects. One-third of the epileptic patients showed elevated plasma HDL cholesterol levels. Female epileptics had higher plasma HDL cholesterol than the normolipidemic healthy subjects. Epileptics with elevated triglyceride or a combination of elevated triglyceride and cholesterol had a lower plasma HDL cholesterol level than normolipidemic patients with epilepsy. HDL cholesterol level in epileptics with high serum cholesterol did not diverge from the level in epileptics with normal serum triglyceride and cholesterol. The results show significant differences of plasma HDL cholesterol between epileptic patients and normolipidemic healthy controls on one hand, and between epileptics with altered and epileptics with normal serum lipid levels on the other. The findings suggest that the increase of plasma HDL cholesterol level in epileptics undergoing anticonvulsant treatment is influenced by endogenous triglyceride metabolism.", "contents": "Plasma HDL cholesterol in epileptics with elevated triglyceride and cholesterol. Due to the metabolic changes induced, e.g. in the liver by anti-epileptic drugs, the significance of high serum triglyceride and cholesterol in epileptics was studied and the plasma HDL cholesterol level was compared in 190 epileptic patients with elevated or normal triglyceride and cholesterol, with the corresponding values in 43 healthy subjects. One-third of the epileptic patients showed elevated plasma HDL cholesterol levels. Female epileptics had higher plasma HDL cholesterol than the normolipidemic healthy subjects. Epileptics with elevated triglyceride or a combination of elevated triglyceride and cholesterol had a lower plasma HDL cholesterol level than normolipidemic patients with epilepsy. HDL cholesterol level in epileptics with high serum cholesterol did not diverge from the level in epileptics with normal serum triglyceride and cholesterol. The results show significant differences of plasma HDL cholesterol between epileptic patients and normolipidemic healthy controls on one hand, and between epileptics with altered and epileptics with normal serum lipid levels on the other. The findings suggest that the increase of plasma HDL cholesterol level in epileptics undergoing anticonvulsant treatment is influenced by endogenous triglyceride metabolism."}
{"id": "PMID:227223", "title": "Pulsatile tinnitus and therapeutic embolization.", "content": "Fifteen patients with disabling pulse-synchronous tinnitus were investigated with super-selective angiography demonstrating an arteriovenous malformation in 8 cases, chemodectoma of the jugular bulb in 3, and a local arterial stenosis in one case. In 12 of these cases the murmur could be registered objectively, while in the 3 cases with a negative angiographic finding no such murmur could be heard, an observation which may be of importance when selecting patients for further angiographic examination. The cases with a tumour and those with an arteriovenous malformation were all treated with gelatin sponge embolizatioected cases embolization is recommended alone or in combination with surgery.", "contents": "Pulsatile tinnitus and therapeutic embolization. Fifteen patients with disabling pulse-synchronous tinnitus were investigated with super-selective angiography demonstrating an arteriovenous malformation in 8 cases, chemodectoma of the jugular bulb in 3, and a local arterial stenosis in one case. In 12 of these cases the murmur could be registered objectively, while in the 3 cases with a negative angiographic finding no such murmur could be heard, an observation which may be of importance when selecting patients for further angiographic examination. The cases with a tumour and those with an arteriovenous malformation were all treated with gelatin sponge embolizatioected cases embolization is recommended alone or in combination with surgery."}
{"id": "PMID:227224", "title": "Effects of glucocorticoids on differentiation of zona glomerulosa of fetal adrenal cortex of rats.", "content": "The tissue differentiation of the zona glomerulosa of the fetal adrenal cortex of rats was studied by giving experimental treatments to the fetus in vivo. A low-glucocorticoid-condition was given to the fetus by bilateral adrenalectomy of pregnant rats for removing exogenous glucocorticoids from the fetus, and by brain aspiration of the fetuses for removing the fetal pituitary gland (ACTH) and endogenous glucocorticoids. When the fetus was placed under a low-glucocorticoid-condition for the last couple of days of gestation, poor differentiation of the zona glomerulosa occurred specifically in the fetal adrenal cortex. The degree of the poor differentiation seemed to be proportional to the duration of the low-glucocorticoid-condition. Supplemental administration of glucocorticoids could prevent this poor differentiation of the zona glomerulosa. These results indicate that the tissue differentiation of the zona glomerulosa of the fetal adrenal cortex depends much on glucocorticoids.", "contents": "Effects of glucocorticoids on differentiation of zona glomerulosa of fetal adrenal cortex of rats. The tissue differentiation of the zona glomerulosa of the fetal adrenal cortex of rats was studied by giving experimental treatments to the fetus in vivo. A low-glucocorticoid-condition was given to the fetus by bilateral adrenalectomy of pregnant rats for removing exogenous glucocorticoids from the fetus, and by brain aspiration of the fetuses for removing the fetal pituitary gland (ACTH) and endogenous glucocorticoids. When the fetus was placed under a low-glucocorticoid-condition for the last couple of days of gestation, poor differentiation of the zona glomerulosa occurred specifically in the fetal adrenal cortex. The degree of the poor differentiation seemed to be proportional to the duration of the low-glucocorticoid-condition. Supplemental administration of glucocorticoids could prevent this poor differentiation of the zona glomerulosa. These results indicate that the tissue differentiation of the zona glomerulosa of the fetal adrenal cortex depends much on glucocorticoids."}
{"id": "PMID:227225", "title": "Ultrastructure of mesodermal mixed tumor of the uterus.", "content": "A case of mesodermal mixed tumor arising in the uterus of a 57-year-old woman is presented. The tumor was a mixture of adenocarcinoma with occasional squamous metaplasia, stromal sarcoma, myxosarcoma and chondrosarcoma. Light and electron microscopic examinations of the tumor revealed close transition between stromal sarcomatous component and each of other sarcomatous and carcinomatous component. The histogenesis of mixed mesodermal tumor was discussed and it was concluded that the tumor might be derived from endometrial stromal cell which possessed the pluripotency to differentiate toward various epithelial and mesenchymal tissues including the heterologous mesenchymal tissue.", "contents": "Ultrastructure of mesodermal mixed tumor of the uterus. A case of mesodermal mixed tumor arising in the uterus of a 57-year-old woman is presented. The tumor was a mixture of adenocarcinoma with occasional squamous metaplasia, stromal sarcoma, myxosarcoma and chondrosarcoma. Light and electron microscopic examinations of the tumor revealed close transition between stromal sarcomatous component and each of other sarcomatous and carcinomatous component. The histogenesis of mixed mesodermal tumor was discussed and it was concluded that the tumor might be derived from endometrial stromal cell which possessed the pluripotency to differentiate toward various epithelial and mesenchymal tissues including the heterologous mesenchymal tissue."}
{"id": "PMID:227226", "title": "ELISA for herpes simplex virus (HSV) type-specific antibodies in human sera using HSV type 1 and type 2 polyspecific antigens blocked with type-heterologous rabbit antibodies.", "content": "Crude antigenic preparations made from rabbit cornea cells infected with either HSV type 1 or type 2 could be used in ELISA for titration of HSV type-specific antibodies in human sera. After immunochemical binding of the crude HSV antigens in microtitre wells by use of type-homologous rabbit antibodies, type-common antigenic sties were blocked with type-heterologous rabbit antibodies. Titration of human sera in this system showed that high concentrations of type heterologous rabbit antibodies were capable of completely blocking type-common antigenic sites, while leaving type-specific antigenic sites unblocked and capable of reacting with human antibodies. Thus HSV type-specific antibodies in human sera could be measured in ELISA without the use of purified typespecific antigens.", "contents": "ELISA for herpes simplex virus (HSV) type-specific antibodies in human sera using HSV type 1 and type 2 polyspecific antigens blocked with type-heterologous rabbit antibodies. Crude antigenic preparations made from rabbit cornea cells infected with either HSV type 1 or type 2 could be used in ELISA for titration of HSV type-specific antibodies in human sera. After immunochemical binding of the crude HSV antigens in microtitre wells by use of type-homologous rabbit antibodies, type-common antigenic sties were blocked with type-heterologous rabbit antibodies. Titration of human sera in this system showed that high concentrations of type heterologous rabbit antibodies were capable of completely blocking type-common antigenic sites, while leaving type-specific antigenic sites unblocked and capable of reacting with human antibodies. Thus HSV type-specific antibodies in human sera could be measured in ELISA without the use of purified typespecific antigens."}
{"id": "PMID:227227", "title": "Influence of diethyldithiocarbamate (DDC) on the memory-facilitating effect of some central stimulants.", "content": "Diethyldithiocarbamate (DDC) introduced in a dose of 400 mg/kg 3 hours before training slightly deteriorates learning in albino rats in a maze. Upon testing 24 hours and 14 days after training, DDC is found to impair markedly the retention indices, when introduced both before and immediately after the end of the training. On the background of DDC, the stimulants caffeine, strychnine, amphetamine, echinopsine and centredrine do not manifest their typical memory-facilitating effect. According to data from the literature and from our previous experiments it is known that the DDC dose used lowers the noradrenaline level in the brain by more than 50 per cent. This suggests that the realization of the memory-facilitating effect of these central stimulants with different basic mechanisms of action requires optimum functional activity of the noradrenergic brain system, as well as this has been established in other experiments for the cholinergic system.", "contents": "Influence of diethyldithiocarbamate (DDC) on the memory-facilitating effect of some central stimulants. Diethyldithiocarbamate (DDC) introduced in a dose of 400 mg/kg 3 hours before training slightly deteriorates learning in albino rats in a maze. Upon testing 24 hours and 14 days after training, DDC is found to impair markedly the retention indices, when introduced both before and immediately after the end of the training. On the background of DDC, the stimulants caffeine, strychnine, amphetamine, echinopsine and centredrine do not manifest their typical memory-facilitating effect. According to data from the literature and from our previous experiments it is known that the DDC dose used lowers the noradrenaline level in the brain by more than 50 per cent. This suggests that the realization of the memory-facilitating effect of these central stimulants with different basic mechanisms of action requires optimum functional activity of the noradrenergic brain system, as well as this has been established in other experiments for the cholinergic system."}
{"id": "PMID:227229", "title": "A case of alcoholic liver injury with an unusual polyacrylamide-gel disc-electrophoretic pattern of serum lipoproteins.", "content": "An unusual lipoprotein pattern on polyacrylamide-gel disc-electrophoresis was observed in 37 year-old male diagnosed as alcoholic liver injury. The electrophoretic lipoprotein pattern consisted of a major band of pre-beta mobility and minor intermediate, fast-beta and slow-alpha bands. The normal beta band was virtually absent and the alpha band was diminished. The abnormal lipoprotein pattern was observed one week after discontinuing alcohol consumption when marked hypertriglyceridemia demonstrated earlier had already normalized leaving a moderate hypercholesterolemia with reduced esterified cholesterol and abnormal liver function tests. The lipoprotein abnormalities were completely normal one month later. The appearance of a major pre-beta band with normal triglyceride and high cholesterol levels is discussed in relation to the formation of larger triglyceride-rich LDL particles in recovery from alcoholic hepatitis.", "contents": "A case of alcoholic liver injury with an unusual polyacrylamide-gel disc-electrophoretic pattern of serum lipoproteins. An unusual lipoprotein pattern on polyacrylamide-gel disc-electrophoresis was observed in 37 year-old male diagnosed as alcoholic liver injury. The electrophoretic lipoprotein pattern consisted of a major band of pre-beta mobility and minor intermediate, fast-beta and slow-alpha bands. The normal beta band was virtually absent and the alpha band was diminished. The abnormal lipoprotein pattern was observed one week after discontinuing alcohol consumption when marked hypertriglyceridemia demonstrated earlier had already normalized leaving a moderate hypercholesterolemia with reduced esterified cholesterol and abnormal liver function tests. The lipoprotein abnormalities were completely normal one month later. The appearance of a major pre-beta band with normal triglyceride and high cholesterol levels is discussed in relation to the formation of larger triglyceride-rich LDL particles in recovery from alcoholic hepatitis."}
{"id": "PMID:227230", "title": "Lipoprotein abnormalities in cholestasis. I. Electrophoretic and ultracentrifugal analyses.", "content": "The alterations of lipid composition in sera of patients with liver diseases, particularly intrahepatic cholestasis and biliary obstruction, were studied by ultracentrifugation and polyacrylamide-gel disc-electrophoresis of lipoproteins and apoproteins. The elevation of serum cholesterol in intrahepatic cholestasis was greater than in biliary obstruction. The appearance of lipoprotein X in obstructive disease accounted for most of the increased cholesterol. The level of non-lipoprotein X cholesterol in intrahepatic cholestasis was significantly elevated, this being in part ascribed to the appearance of a new class of cholestatic lipoprotein, Slow-migrating HDL. The electrophoretic pattern of lipoprotein in cholestasis was generally characterized by a decrease in alpha band intensity and, in some types of cholestasis, by the appearance of Slow-migrating HDL. In addition, other abnormal lipoproteins exhibiting the characteristics of triglyceride-rich LDL (LP-Y), LP-X-like HDL and LDL-like HDL were found in some cases of intrahepatic cholestasis and biliary obstruction.", "contents": "Lipoprotein abnormalities in cholestasis. I. Electrophoretic and ultracentrifugal analyses. The alterations of lipid composition in sera of patients with liver diseases, particularly intrahepatic cholestasis and biliary obstruction, were studied by ultracentrifugation and polyacrylamide-gel disc-electrophoresis of lipoproteins and apoproteins. The elevation of serum cholesterol in intrahepatic cholestasis was greater than in biliary obstruction. The appearance of lipoprotein X in obstructive disease accounted for most of the increased cholesterol. The level of non-lipoprotein X cholesterol in intrahepatic cholestasis was significantly elevated, this being in part ascribed to the appearance of a new class of cholestatic lipoprotein, Slow-migrating HDL. The electrophoretic pattern of lipoprotein in cholestasis was generally characterized by a decrease in alpha band intensity and, in some types of cholestasis, by the appearance of Slow-migrating HDL. In addition, other abnormal lipoproteins exhibiting the characteristics of triglyceride-rich LDL (LP-Y), LP-X-like HDL and LDL-like HDL were found in some cases of intrahepatic cholestasis and biliary obstruction."}
{"id": "PMID:227231", "title": "The mechanism of the release of hepatic enzymes in various liver diseases. 1. Alterations in cytoplasmic and mitochondrial enzyme activities in serum.", "content": "Serum glutamic oxaloacetic transaminase (GOT), mitochondrial GOT (GOTm), glutamic-pyruvic transaminase (GPT) and glutamate dehydrogenase activities were determined in 43 healthy controls and in 280 cases of liver diseases. A simplified column chromatographic method coupled with UV assay was employed for separation of GOTm. The activity was measured by following decrease in abosrbance of NADH at 340 nm. The lowest activity of GOTm determined with a coefficient of variation below 10% was 6 mIU/ml. High GOTm activities were found in acute hepatitis (acute stage), subacute hepatitis and primary biliary cirrhosis and were generally associated with high total GOT (GOTt) activities. The activity ratio of GOTm/GOTt varied depending on the stage and severity of liver diseases. The GOTm/GOTt ratio was decreased in acute, fulminant and subacute hepatitides. No significant reduction in the ratio was found in bile duct obstruction, alcoholic liver injury or metastatic liver cancer. Although relatively high GOTm/GOTt ratios were found in some patients with severe hepatic injury, they had no definite association with poor prognosis. These results indicate that the marked elevation in GOTt over GPT in advanced chronic hepatitis, liver cirrhosis and primary hepatoma was mainly due to preferential leakage of cytoplasmic GOT (GOTs).", "contents": "The mechanism of the release of hepatic enzymes in various liver diseases. 1. Alterations in cytoplasmic and mitochondrial enzyme activities in serum. Serum glutamic oxaloacetic transaminase (GOT), mitochondrial GOT (GOTm), glutamic-pyruvic transaminase (GPT) and glutamate dehydrogenase activities were determined in 43 healthy controls and in 280 cases of liver diseases. A simplified column chromatographic method coupled with UV assay was employed for separation of GOTm. The activity was measured by following decrease in abosrbance of NADH at 340 nm. The lowest activity of GOTm determined with a coefficient of variation below 10% was 6 mIU/ml. High GOTm activities were found in acute hepatitis (acute stage), subacute hepatitis and primary biliary cirrhosis and were generally associated with high total GOT (GOTt) activities. The activity ratio of GOTm/GOTt varied depending on the stage and severity of liver diseases. The GOTm/GOTt ratio was decreased in acute, fulminant and subacute hepatitides. No significant reduction in the ratio was found in bile duct obstruction, alcoholic liver injury or metastatic liver cancer. Although relatively high GOTm/GOTt ratios were found in some patients with severe hepatic injury, they had no definite association with poor prognosis. These results indicate that the marked elevation in GOTt over GPT in advanced chronic hepatitis, liver cirrhosis and primary hepatoma was mainly due to preferential leakage of cytoplasmic GOT (GOTs)."}
{"id": "PMID:227232", "title": "Effect of nicomol on HDL cholesterol level.", "content": "In cardiovascular diseases with potential atherosclerosis, the serum concentration of HDL cholesterol as determined by a precipitation method with dextran sulfate and Mg++ was lower while that of total cholesterol was normal or elevated. Treatment with a daily dose of 1,200 mg of Nicomol, a derivative of nicotinic acid, for 1 to 3 months increased the mean HDL cholesterol level by 3 to 5 mg/dl and reduced the total cholesterol level by 14 to 15 mg/dl and total/HDL cholesterol ratio by 0.8 (3 months) to 0.9 (1 month, p less than 0.05). Similar decreases in HDL cholesterol concentration were also found in parenchymal and obstructive liver diseases with normal total cholesterol values except in fulminant hepatitis and intrahepatic cholestasis.", "contents": "Effect of nicomol on HDL cholesterol level. In cardiovascular diseases with potential atherosclerosis, the serum concentration of HDL cholesterol as determined by a precipitation method with dextran sulfate and Mg++ was lower while that of total cholesterol was normal or elevated. Treatment with a daily dose of 1,200 mg of Nicomol, a derivative of nicotinic acid, for 1 to 3 months increased the mean HDL cholesterol level by 3 to 5 mg/dl and reduced the total cholesterol level by 14 to 15 mg/dl and total/HDL cholesterol ratio by 0.8 (3 months) to 0.9 (1 month, p less than 0.05). Similar decreases in HDL cholesterol concentration were also found in parenchymal and obstructive liver diseases with normal total cholesterol values except in fulminant hepatitis and intrahepatic cholestasis."}
{"id": "PMID:227233", "title": "Small cell carcinoma of the lung: relation of calcitonin to bone marrow metastases, parathormone and gastrin.", "content": "The relations of calcitonin concentrations to the presence of bone marrow metastases and to the concentrations of calcium, parathormone and gastrin in serum were investigated in 74 untreated patients with small cell carcinoma of the lung. Calcitonin concentrations were enhanced in two thirds of the patients, while serum calcium concentrations were normal in all. In 19 of 57 patients parathormone concentrations were slightly above the normal range, but the concentrations of parathormone and calcitonin were not correlated. Bone marrow metastases had no influence on the concentration of serum calcitonin. Finally, a small inverse correlation between the concentrations of gastrin and calcitonin in serum was observed. The results resemble those of the calcitonin-producing medullary carcinoma of the thyroid, supporting the suggestion of an ectopic source of hypercalcitoninemia in small cell carcinoma of the lung.", "contents": "Small cell carcinoma of the lung: relation of calcitonin to bone marrow metastases, parathormone and gastrin. The relations of calcitonin concentrations to the presence of bone marrow metastases and to the concentrations of calcium, parathormone and gastrin in serum were investigated in 74 untreated patients with small cell carcinoma of the lung. Calcitonin concentrations were enhanced in two thirds of the patients, while serum calcium concentrations were normal in all. In 19 of 57 patients parathormone concentrations were slightly above the normal range, but the concentrations of parathormone and calcitonin were not correlated. Bone marrow metastases had no influence on the concentration of serum calcitonin. Finally, a small inverse correlation between the concentrations of gastrin and calcitonin in serum was observed. The results resemble those of the calcitonin-producing medullary carcinoma of the thyroid, supporting the suggestion of an ectopic source of hypercalcitoninemia in small cell carcinoma of the lung."}
{"id": "PMID:227234", "title": "Streptozotocin treatment of a pancreatic tumour producing VIP and gastrin associated with Verner-Morrison syndrome.", "content": "A 57-year-old male patient with metastasizing non-beta islet cell carcinoma of the pancreas is described. Both gastrin and VIP levels were elevated and the patient suffered from a syndrome of pancreatic cholera and hyperacidity. The tumour contained gastrin and VIP as demonstrated by immunofluorescence. The patient also had a history of familial renal stone formation and parathyroid nodular hyperplasia. Resection of pancreatic tumour in 1973 resulted in four years without symptoms. In 1977 definite signs of multiple hepatic metastases appeared. These signs disappeared after streptozotocin given in a dosage of 2 g three times at weekly intervals. The patient had remained well for 20 months after this treatment. The causative agents for the clinical syndrome in this case are discussed in view of circulating hormone levels.", "contents": "Streptozotocin treatment of a pancreatic tumour producing VIP and gastrin associated with Verner-Morrison syndrome. A 57-year-old male patient with metastasizing non-beta islet cell carcinoma of the pancreas is described. Both gastrin and VIP levels were elevated and the patient suffered from a syndrome of pancreatic cholera and hyperacidity. The tumour contained gastrin and VIP as demonstrated by immunofluorescence. The patient also had a history of familial renal stone formation and parathyroid nodular hyperplasia. Resection of pancreatic tumour in 1973 resulted in four years without symptoms. In 1977 definite signs of multiple hepatic metastases appeared. These signs disappeared after streptozotocin given in a dosage of 2 g three times at weekly intervals. The patient had remained well for 20 months after this treatment. The causative agents for the clinical syndrome in this case are discussed in view of circulating hormone levels."}
{"id": "PMID:227237", "title": "Viral vaccines under development: a third generation.", "content": "In summary then, my purpose has been two-fold: on the one hand, I have tried to highlight the kinds of basic science advances in both cellular and virologic research that can (and should) be focussed both on vaccines under development and, retrospectively, on those whose origins were strictly empiric. On the other hand, I have attempted a partial survey of some of the prominent members of a potential new generation of vaccines to point out areas where these advances can and should contribute either to progress or to a sense of caution about the further reliance on pure empiricism. It is clear that we are not finished with new viral vaccines. It is equally clear that narrowing the persistent gap between basic science and its application to public health needs will require much energy and attention as vaccine development progresses.", "contents": "Viral vaccines under development: a third generation. In summary then, my purpose has been two-fold: on the one hand, I have tried to highlight the kinds of basic science advances in both cellular and virologic research that can (and should) be focussed both on vaccines under development and, retrospectively, on those whose origins were strictly empiric. On the other hand, I have attempted a partial survey of some of the prominent members of a potential new generation of vaccines to point out areas where these advances can and should contribute either to progress or to a sense of caution about the further reliance on pure empiricism. It is clear that we are not finished with new viral vaccines. It is equally clear that narrowing the persistent gap between basic science and its application to public health needs will require much energy and attention as vaccine development progresses."}
{"id": "PMID:227240", "title": "The role of phosphoenolpyruvate and lactate production in insulin secretion.", "content": "There is a positive correlation between lactate output and insulin secretion but there is no correlation between total islet PEP content and insulin secretion and no correlation between cAMP production and insulin release. Neither PEP or cAMP seem to be primary triggers to insulin release but may rather act as positive modulators of insulin secretion. Potentially, PEP can maintain an elevated cytoplasmic Ca++ concentration by inhibiting Ca++ uptake in the mitochondria, increase the concentration of cAMP in the beta-cells by activating the adenylate cyclase (11) and change the phosphorylation state of the plasma membrane (12). The possible trigger effect of an increased glycolytic flux on insulin secretion may be mediated perhaps via changes in the NADH/NAD+ ratio (13). As regards the mechanism of potentiation of insulin release: in the fed state potentiation may be related to an increased glycolytic flux whereas this is not the case during starvation. Here enhancement of cAMP may play a role.", "contents": "The role of phosphoenolpyruvate and lactate production in insulin secretion. There is a positive correlation between lactate output and insulin secretion but there is no correlation between total islet PEP content and insulin secretion and no correlation between cAMP production and insulin release. Neither PEP or cAMP seem to be primary triggers to insulin release but may rather act as positive modulators of insulin secretion. Potentially, PEP can maintain an elevated cytoplasmic Ca++ concentration by inhibiting Ca++ uptake in the mitochondria, increase the concentration of cAMP in the beta-cells by activating the adenylate cyclase (11) and change the phosphorylation state of the plasma membrane (12). The possible trigger effect of an increased glycolytic flux on insulin secretion may be mediated perhaps via changes in the NADH/NAD+ ratio (13). As regards the mechanism of potentiation of insulin release: in the fed state potentiation may be related to an increased glycolytic flux whereas this is not the case during starvation. Here enhancement of cAMP may play a role."}
{"id": "PMID:227241", "title": "Method for measurement of human urinary kininase activity.", "content": "A method was developed to measure kininase activity in human urine. The method consists of dialysis of human centrifuged urine sample against phosphate buffer and partial fractionation of A-50 Sephadex column. The enzymatic property of urinary kininase, which destroys bradykinin when incubated, is estimated from its effect on a definite amount of bradykinin, using rat uterus.", "contents": "Method for measurement of human urinary kininase activity. A method was developed to measure kininase activity in human urine. The method consists of dialysis of human centrifuged urine sample against phosphate buffer and partial fractionation of A-50 Sephadex column. The enzymatic property of urinary kininase, which destroys bradykinin when incubated, is estimated from its effect on a definite amount of bradykinin, using rat uterus."}
{"id": "PMID:227242", "title": "Components of the kallikrein-kinin system in urine.", "content": "The excretion of kallikrein in urine varies, but the pathophysiologic implications are not clear. To help clarify the role of the urinary kallikrein-kinin system, we have begun to define components of the system as they occur in urine. To minimize artifacts which may arise through extensive purification procedures, we studied urinary protein concentrates prepared by ultrafiltration. The concentrates were separated by chromatography on Sephacryl. Urine contains abundant kininase activity, but in strongly inhibited forms. Kininase II is separable into at least two forms. Another major kininase can hydrolyze benzoyl-Pro-Phe-Arg and is inhibited by arginine but not by BPP9a or SQ 14,225. Its molecular weight is approximately 63,000. A third kininase, not inhibited by BPP9a, is excluded from Sephacryl. Human urine appears to contain only one kallikrein-like enzyme (MW 45,000). In addition, urine contains a protein (MW approximately 80,000) which reacts with trypsin to release bradykinin and which inhibits the hydrolysis of Pro-Phe-Arg-[3H]anilide by urinary kallikrein. Thus, in addition to kallikrein and kinins, urine contains kininogen and at least three kininase enzymes. Urinary ultrafiltrate contains an inhibitory substance (approximately MW 400).", "contents": "Components of the kallikrein-kinin system in urine. The excretion of kallikrein in urine varies, but the pathophysiologic implications are not clear. To help clarify the role of the urinary kallikrein-kinin system, we have begun to define components of the system as they occur in urine. To minimize artifacts which may arise through extensive purification procedures, we studied urinary protein concentrates prepared by ultrafiltration. The concentrates were separated by chromatography on Sephacryl. Urine contains abundant kininase activity, but in strongly inhibited forms. Kininase II is separable into at least two forms. Another major kininase can hydrolyze benzoyl-Pro-Phe-Arg and is inhibited by arginine but not by BPP9a or SQ 14,225. Its molecular weight is approximately 63,000. A third kininase, not inhibited by BPP9a, is excluded from Sephacryl. Human urine appears to contain only one kallikrein-like enzyme (MW 45,000). In addition, urine contains a protein (MW approximately 80,000) which reacts with trypsin to release bradykinin and which inhibits the hydrolysis of Pro-Phe-Arg-[3H]anilide by urinary kallikrein. Thus, in addition to kallikrein and kinins, urine contains kininogen and at least three kininase enzymes. Urinary ultrafiltrate contains an inhibitory substance (approximately MW 400)."}
{"id": "PMID:227243", "title": "Effect of bradykinin to cyclic AMP levels and response of murine lymphocytes.", "content": "No information is available on the pharmacological effect of bradykinin to lymphocytes and immunological responses of them. In this study it was clarified that bradykinin as well as histamine elevated cyclic adenosine 3',5' monophosphate (cAMP) levels of murine splenic or lymph node lymphocytes and mature thymocytes (cortisone-resistant thymus), but did not increase cAMP levels of immature thymocytes as well as histamine. The increased cAMP ratios in T cell-enriched splenic lymphocytes by the impulse of bradykinin were higher than that in splenic and lymph node lymphoid cells by the stimulation of bradykinin. It was also demonstrated that bradykinin as well as histamine suppressed DNA synthesis by mitogenic (PHA-P, Con-A) stimulation of splenic lymphocytes, but not a effect to the response of lymphocytes by mitogenic (LPS) stimulation was observed. These facts suggest that bradykinin may play an important role in the regulation of immunologic lymphocyte responses.", "contents": "Effect of bradykinin to cyclic AMP levels and response of murine lymphocytes. No information is available on the pharmacological effect of bradykinin to lymphocytes and immunological responses of them. In this study it was clarified that bradykinin as well as histamine elevated cyclic adenosine 3',5' monophosphate (cAMP) levels of murine splenic or lymph node lymphocytes and mature thymocytes (cortisone-resistant thymus), but did not increase cAMP levels of immature thymocytes as well as histamine. The increased cAMP ratios in T cell-enriched splenic lymphocytes by the impulse of bradykinin were higher than that in splenic and lymph node lymphoid cells by the stimulation of bradykinin. It was also demonstrated that bradykinin as well as histamine suppressed DNA synthesis by mitogenic (PHA-P, Con-A) stimulation of splenic lymphocytes, but not a effect to the response of lymphocytes by mitogenic (LPS) stimulation was observed. These facts suggest that bradykinin may play an important role in the regulation of immunologic lymphocyte responses."}
{"id": "PMID:227244", "title": "Pulmonary anaphylaxis and the kallikrein-kinin system.", "content": "The kallikrein-kinin system has been thought to participate in the pathogenesis of anaphylaxis. Kallikrein, released from lungs, has been postulated to contribute to cardiovascular collapse. Further to test the hypothesis, we examined for the occurrence of a kallikrein-like enzyme in guinea pig lungs and examined for release of such an enzyme by isolated, perfused lungs of guinea pig sensitized to and challenged with egg albumin. In addition, we treated guinea pigs with the bradykinin potentiating agents, BPP9a and SQ 14,225. In parallel experiments, we examined for effects of non-steroidal anti-inflammatory agents on the supposition that prostaglandin-related substances may mediate or modulate actions of kinins during anaphylaxis. A plasma kallikrein-like enzyme was found in lung homogenates and occurred in concentrations greater than that of plasma itself. Similarly, a store of kininogen occurs in lungs. However, using a sensitive radioassay for kallikrein-like enzymes, we were unable to confirm that antigenic challenge of sensitized lungs causes the release of enzyme into pulmonary venous effluent. Further, we were unable to modify the acute course of anaphylaxis by pretreatment of guinea pigs with bradykinin potentiating agents. However, indomethacin and aspirin at 20-40 mg/kg were found to greatly increase the severity of pulmonary anaphylaxis in terms of increased resistance to ventilation and increased numbers of lung hemorrhages. Paradoxically, aspirin or sodium salicylate at 80-100 mg/kg prevents the characteristic rise of insufflation pressure and the formation of lung hemorrhages.", "contents": "Pulmonary anaphylaxis and the kallikrein-kinin system. The kallikrein-kinin system has been thought to participate in the pathogenesis of anaphylaxis. Kallikrein, released from lungs, has been postulated to contribute to cardiovascular collapse. Further to test the hypothesis, we examined for the occurrence of a kallikrein-like enzyme in guinea pig lungs and examined for release of such an enzyme by isolated, perfused lungs of guinea pig sensitized to and challenged with egg albumin. In addition, we treated guinea pigs with the bradykinin potentiating agents, BPP9a and SQ 14,225. In parallel experiments, we examined for effects of non-steroidal anti-inflammatory agents on the supposition that prostaglandin-related substances may mediate or modulate actions of kinins during anaphylaxis. A plasma kallikrein-like enzyme was found in lung homogenates and occurred in concentrations greater than that of plasma itself. Similarly, a store of kininogen occurs in lungs. However, using a sensitive radioassay for kallikrein-like enzymes, we were unable to confirm that antigenic challenge of sensitized lungs causes the release of enzyme into pulmonary venous effluent. Further, we were unable to modify the acute course of anaphylaxis by pretreatment of guinea pigs with bradykinin potentiating agents. However, indomethacin and aspirin at 20-40 mg/kg were found to greatly increase the severity of pulmonary anaphylaxis in terms of increased resistance to ventilation and increased numbers of lung hemorrhages. Paradoxically, aspirin or sodium salicylate at 80-100 mg/kg prevents the characteristic rise of insufflation pressure and the formation of lung hemorrhages."}
{"id": "PMID:227245", "title": "Altered urinary excretion of human kininase activity in acute myocardial infarction.", "content": "This study concerns the determination of levels of human urinary kininase excretion in acute myocardial infarction (AMI). The results obtained by a biological method show that there is a significant reduction of the enzymatic activity in patients affected by AMI in comparison with normals (6.4 +/- 0.4 ng of destroyed bradykinin/min. versus 164.4 +/- 31.4 ng; P less than 0.001), while urinary kallikrein excretion was close to normal values.", "contents": "Altered urinary excretion of human kininase activity in acute myocardial infarction. This study concerns the determination of levels of human urinary kininase excretion in acute myocardial infarction (AMI). The results obtained by a biological method show that there is a significant reduction of the enzymatic activity in patients affected by AMI in comparison with normals (6.4 +/- 0.4 ng of destroyed bradykinin/min. versus 164.4 +/- 31.4 ng; P less than 0.001), while urinary kallikrein excretion was close to normal values."}
{"id": "PMID:227251", "title": "The role of the kidney in vitamin D metabolism.", "content": "The kidney should be regarded as an organ of central importance in the regulation of calcium metabolism. Its secretion product, 1 alpha,25(OH)2D3, is regulated by several factors, including the calcium and phosphorus content of the diet, parathyroid hormone and the level of 1 alpha,25(OH)2D3 itself. The main occasions in health where 1 alpha,25(OH)2D3 secretion is enhanced are during growth and reproduction. In these situations the secretion of this new renal hormone is under at least partial control of growth hormone and prolactin.", "contents": "The role of the kidney in vitamin D metabolism. The kidney should be regarded as an organ of central importance in the regulation of calcium metabolism. Its secretion product, 1 alpha,25(OH)2D3, is regulated by several factors, including the calcium and phosphorus content of the diet, parathyroid hormone and the level of 1 alpha,25(OH)2D3 itself. The main occasions in health where 1 alpha,25(OH)2D3 secretion is enhanced are during growth and reproduction. In these situations the secretion of this new renal hormone is under at least partial control of growth hormone and prolactin."}
{"id": "PMID:227252", "title": "Metabolic and cellular activity of vitamin D.", "content": "Most of the effects of vitamin D on calcium and phosphorus homeostasis result from an increase in intestinal absorption of calcium and phosphorus and from bone mobilization. These effects are due to 1,25(OH)2D3, one of the renal vitamin D metabolites. Besides ionic mobilization, vitamin D may exert additional effects on bone which depend on metabolites other than 1,25(OH)2D3. Kidneys, parathyroid glands and muscle are probably target organs for vitamin D. The metabolite(s) responsible for these actions remain unknown.", "contents": "Metabolic and cellular activity of vitamin D. Most of the effects of vitamin D on calcium and phosphorus homeostasis result from an increase in intestinal absorption of calcium and phosphorus and from bone mobilization. These effects are due to 1,25(OH)2D3, one of the renal vitamin D metabolites. Besides ionic mobilization, vitamin D may exert additional effects on bone which depend on metabolites other than 1,25(OH)2D3. Kidneys, parathyroid glands and muscle are probably target organs for vitamin D. The metabolite(s) responsible for these actions remain unknown."}
{"id": "PMID:227254", "title": "Pathways of arachidonic acid metabolism and modulation by drugs.", "content": "The AA cascade in addition to producing various oxygenation products concomitantly yields an oxygen radical. This oxidant selectively deactivates the cyclooxygenase, peroxidase and PGI2 synthetase components whereas TXA2 synthetase is resistant to this oxidant. On the basis of available data it is not possible to assign an inflammatory inducing role to this oxidant on the basis of these actions. Other loci of action must be involved. Among the possibilities are the elements involved in the release of arachidonic acid. Studies relating to this possibility are examined in this report.", "contents": "Pathways of arachidonic acid metabolism and modulation by drugs. The AA cascade in addition to producing various oxygenation products concomitantly yields an oxygen radical. This oxidant selectively deactivates the cyclooxygenase, peroxidase and PGI2 synthetase components whereas TXA2 synthetase is resistant to this oxidant. On the basis of available data it is not possible to assign an inflammatory inducing role to this oxidant on the basis of these actions. Other loci of action must be involved. Among the possibilities are the elements involved in the release of arachidonic acid. Studies relating to this possibility are examined in this report."}
{"id": "PMID:227257", "title": "[Action of vitamin D and E on the erythrocyte membrane. II. Morphological changes in the erythrocytes studied by transmission electron microscopy].", "content": "Man, rabbit, guinea-pig erythrocytes treated \"in vitro\" with high doses of cholecalcipherol or alpha-tocopherol release K+ and haemoglobin and show ultrastructural damages. These damages consist in a change of the red cells profile as well as in the desappearance of the glycocalix, in alterations of the membrane and of the cortical cytoplasm structure. These ultrastructural alterations are of a different degree, depending on the animal species; they partly resemble the erythrocyte changes induced by retinol. Our results are in partial agreement with the Dingle and Lucy's hypothesis on the common action of liposoluble vitamines on the erythrocyte membrane.", "contents": "[Action of vitamin D and E on the erythrocyte membrane. II. Morphological changes in the erythrocytes studied by transmission electron microscopy]. Man, rabbit, guinea-pig erythrocytes treated \"in vitro\" with high doses of cholecalcipherol or alpha-tocopherol release K+ and haemoglobin and show ultrastructural damages. These damages consist in a change of the red cells profile as well as in the desappearance of the glycocalix, in alterations of the membrane and of the cortical cytoplasm structure. These ultrastructural alterations are of a different degree, depending on the animal species; they partly resemble the erythrocyte changes induced by retinol. Our results are in partial agreement with the Dingle and Lucy's hypothesis on the common action of liposoluble vitamines on the erythrocyte membrane."}
{"id": "PMID:227258", "title": "Application of case series review results to the evaluation of individual cases in diagnostic radiology.", "content": "Probability theory provides a simple method for physicians to use their \"intellectual linkages\" to their past clinical experience in making current diagnoses. Only a pencil and paper are required for making a few likelihood calculations. To illustrate this method, evaluation was done of a new diagnostic sign (presence of knee ossification centers) for differentiating rubella from cytomegalovirus infection in young infants. Two practical questions can be answered by use of this method for calculating probabilities: (1) How certain can one be about either diagnosis when centers are present or absent? (2) How can other radiologists apply these results to their individual cases?", "contents": "Application of case series review results to the evaluation of individual cases in diagnostic radiology. Probability theory provides a simple method for physicians to use their \"intellectual linkages\" to their past clinical experience in making current diagnoses. Only a pencil and paper are required for making a few likelihood calculations. To illustrate this method, evaluation was done of a new diagnostic sign (presence of knee ossification centers) for differentiating rubella from cytomegalovirus infection in young infants. Two practical questions can be answered by use of this method for calculating probabilities: (1) How certain can one be about either diagnosis when centers are present or absent? (2) How can other radiologists apply these results to their individual cases?"}
{"id": "PMID:227261", "title": "Relationship between extent of coronary artery disease and correlative risk factors.", "content": "An analysis was made of correlative factors which might be related to the angiographically measured extent of coronary artery disease in 140 patients. All patients presented with clinically important chest pain. Thirty-three had a normal coronary arteriogram. The extent of the atheromatous process was measured precisely at angiography by three different techniques. A coronary score, based on the percentage of luminal narrowing, was found to be best suited for the analysis. The most important contributory factors to the severity of atherosclerosis was duration of clinical history, number of previous myocardial infarctions, and male sex, but more specifically elevation of serum cholesterol and diabetes mellitus. Cigarette smoking, obesity, hypertension, a family history of atherosclerosis, and elevated serum triglycerides had a positive influence but this was not statistically significant.", "contents": "Relationship between extent of coronary artery disease and correlative risk factors. An analysis was made of correlative factors which might be related to the angiographically measured extent of coronary artery disease in 140 patients. All patients presented with clinically important chest pain. Thirty-three had a normal coronary arteriogram. The extent of the atheromatous process was measured precisely at angiography by three different techniques. A coronary score, based on the percentage of luminal narrowing, was found to be best suited for the analysis. The most important contributory factors to the severity of atherosclerosis was duration of clinical history, number of previous myocardial infarctions, and male sex, but more specifically elevation of serum cholesterol and diabetes mellitus. Cigarette smoking, obesity, hypertension, a family history of atherosclerosis, and elevated serum triglycerides had a positive influence but this was not statistically significant."}
{"id": "PMID:227262", "title": "Role of calcium and cyclic adenosine 3':5' monophosphate in regulating smooth muscle contraction. Mechanisms of excitation-contraction coupling in smooth muscle.", "content": "Caclium initiates smooth muscle contraction by activating an enzyme, myosin light chain kinase. This enzyme catalyzes the transfer of phosphate from adenosine triphosphate to the 20,000 dalton light chain of myosin. In its phosphorylated form myosin interacts with actin to produce muscle contraction. The mechanism by which calcium activates myosin kinase requires (1) the binding of calcium to a 16,500 dalton calcium-binding protein (calmodulin), and (2) the binding of calmodulin-calcium to a 125,000 dalton catalytic subunit. This two protein complex is the active form of myosin light chain kinase. Smooth muscle relaxation is mediated by cyclic adenosine 3':5' monophosphate (cyclic AMP). One nechanism by which the latter may exert a direct effect on actin-myosin interaction is through the activation of a cyclic AMP-dependent protein kinase that can phosphorylate the 125,000 dalton component of myosin light chain kinase. Phosphorylation of myosin light chain kinase decreases the activity of the enzyme, thus favoring the unphosphorylated form of myosin, which cannot interact with actin to produce smooth muscle contraction.", "contents": "Role of calcium and cyclic adenosine 3':5' monophosphate in regulating smooth muscle contraction. Mechanisms of excitation-contraction coupling in smooth muscle. Caclium initiates smooth muscle contraction by activating an enzyme, myosin light chain kinase. This enzyme catalyzes the transfer of phosphate from adenosine triphosphate to the 20,000 dalton light chain of myosin. In its phosphorylated form myosin interacts with actin to produce muscle contraction. The mechanism by which calcium activates myosin kinase requires (1) the binding of calcium to a 16,500 dalton calcium-binding protein (calmodulin), and (2) the binding of calmodulin-calcium to a 125,000 dalton catalytic subunit. This two protein complex is the active form of myosin light chain kinase. Smooth muscle relaxation is mediated by cyclic adenosine 3':5' monophosphate (cyclic AMP). One nechanism by which the latter may exert a direct effect on actin-myosin interaction is through the activation of a cyclic AMP-dependent protein kinase that can phosphorylate the 125,000 dalton component of myosin light chain kinase. Phosphorylation of myosin light chain kinase decreases the activity of the enzyme, thus favoring the unphosphorylated form of myosin, which cannot interact with actin to produce smooth muscle contraction."}
{"id": "PMID:227263", "title": "Abnormal technetium-99m pyrophosphate images in unstable angina: ischemia versus infarction?", "content": "There is controversy concerning the specificity of myocardial infarct imaging with technetium-99m pyrophosphate due to the high frequency of false positive images, especially in patients with unstable angina. In this study technetium-99m pyrophosphate images were compared with frequent determinations of plasma creatine kinase, MB isoenzyme (MB CK) activity in 116 patients admitted with the diagnosis of unstable angina. It was hypothesized that frequent measurement of MB CK activity, a sensitive and specific marker for myocardial necrosis, using sensitive assay techniques would detect small amounts of myocardial necrosis which might have been unrecognized by conventional clinical methods. The scintigraphic results and isoenzyme determinations agreed in 88 percent of patients; both tests were normal in 69 percent and both were abnormal, indicating acute myocardial infarcation, in 19 percent of patients. In the remaining 14 patients (12 percent), the scans were abnormal, but MB CK activity was normal. In five of these patients (4 percent), abnormal scintigrams presumably reflected persistent scan positivity after previous myocardial infarction. Only the remaining nine patients (8 percent) could be classified as having unexplained false positive scans, a frequency substantially less than that reported by other investigators who based the diagnosis of myocardial infarction on conventional clinical criteria. These results suggest that abnormal technetium-99m pyrophosphate images in patients with unstable angina generally indicate myocardial necrosis.", "contents": "Abnormal technetium-99m pyrophosphate images in unstable angina: ischemia versus infarction? There is controversy concerning the specificity of myocardial infarct imaging with technetium-99m pyrophosphate due to the high frequency of false positive images, especially in patients with unstable angina. In this study technetium-99m pyrophosphate images were compared with frequent determinations of plasma creatine kinase, MB isoenzyme (MB CK) activity in 116 patients admitted with the diagnosis of unstable angina. It was hypothesized that frequent measurement of MB CK activity, a sensitive and specific marker for myocardial necrosis, using sensitive assay techniques would detect small amounts of myocardial necrosis which might have been unrecognized by conventional clinical methods. The scintigraphic results and isoenzyme determinations agreed in 88 percent of patients; both tests were normal in 69 percent and both were abnormal, indicating acute myocardial infarcation, in 19 percent of patients. In the remaining 14 patients (12 percent), the scans were abnormal, but MB CK activity was normal. In five of these patients (4 percent), abnormal scintigrams presumably reflected persistent scan positivity after previous myocardial infarction. Only the remaining nine patients (8 percent) could be classified as having unexplained false positive scans, a frequency substantially less than that reported by other investigators who based the diagnosis of myocardial infarction on conventional clinical criteria. These results suggest that abnormal technetium-99m pyrophosphate images in patients with unstable angina generally indicate myocardial necrosis."}
{"id": "PMID:227264", "title": "Acute lymphoblastic leukemia, hand-mirror variant. A detailed ultrastructural study.", "content": "The hand-mirror cell in acute lymphoblastic leukemia may have important immunologic, pathogenic, and prognostic implications. To learn more about this cell, a detailed ultrastructural analysis was performed. Fifty electronmicrographs of lymphoblasts from an untreated patient with acute lymphoblastic leukemia with numerous hand-mirror cells in the bone marrow were compared with 60 electronmicrographs of lymphoblasts from six patients with classic acute lymphoblastic leukemia. The unique qualitative ultrastructural features of the hand-mirror cells were the presence of undamaged mitochondria and uropods (handles) with terminal microspikes containing circular organized arrangement of 50-A microfilaments. Quantitative differences between hand-mirror cells and lymphoblasts were observed in nuclear perimeters (P less than 0.0001), nuclear lengths (P less than 0.001), cytoplasmic lengths (P less than 0.0002), nuclear-cytoplasmic length ratios (P less than 0.0001), and numbers of mitochondria (P less than 0.002). These findings indicate that hand-mirror cells contain ultrastructural components that are related to cell motility and the immunologic process. These results are significant in that the hand-mirror cells may be associated with an immunologic mechanism that is involved in leukemogenesis.", "contents": "Acute lymphoblastic leukemia, hand-mirror variant. A detailed ultrastructural study. The hand-mirror cell in acute lymphoblastic leukemia may have important immunologic, pathogenic, and prognostic implications. To learn more about this cell, a detailed ultrastructural analysis was performed. Fifty electronmicrographs of lymphoblasts from an untreated patient with acute lymphoblastic leukemia with numerous hand-mirror cells in the bone marrow were compared with 60 electronmicrographs of lymphoblasts from six patients with classic acute lymphoblastic leukemia. The unique qualitative ultrastructural features of the hand-mirror cells were the presence of undamaged mitochondria and uropods (handles) with terminal microspikes containing circular organized arrangement of 50-A microfilaments. Quantitative differences between hand-mirror cells and lymphoblasts were observed in nuclear perimeters (P less than 0.0001), nuclear lengths (P less than 0.001), cytoplasmic lengths (P less than 0.0002), nuclear-cytoplasmic length ratios (P less than 0.0001), and numbers of mitochondria (P less than 0.002). These findings indicate that hand-mirror cells contain ultrastructural components that are related to cell motility and the immunologic process. These results are significant in that the hand-mirror cells may be associated with an immunologic mechanism that is involved in leukemogenesis."}
{"id": "PMID:227265", "title": "Cytomegalovirus encephalitis associated with thymoma and immunoglobulin deficiency.", "content": "The clinical and immunologic findings in an elderly woman with thymoma and immunoglobulin deficiency in whom cytomegalovirus (CMV) encephalitis developed are described. The patient had absent serum immunoglobulins and no circulating immunoglobulin-bearing lymphocytes. Complement receptor-bearing lymphocytes were present in the peripheral blood, and circulating T lymphocyte numbers were within normal limits. She was anergic to a battery of skin test antigens, and her lymphocytes in vitro showed a selective unresponsiveness to CMV antigen while responding normally to phytohemagglutinin and streptokinase. The course of the encephalitis was progressive with quadriplegia, aphasia and coma developing within six months of onset of symptoms. This is the fifth reported case documenting an association between CMV infection and the syndrome of thymoma with immunoglobulin deficiency, but the first report of fatal CMV encephalitis in a patient with thymoma and immunoglobulin deficiency.", "contents": "Cytomegalovirus encephalitis associated with thymoma and immunoglobulin deficiency. The clinical and immunologic findings in an elderly woman with thymoma and immunoglobulin deficiency in whom cytomegalovirus (CMV) encephalitis developed are described. The patient had absent serum immunoglobulins and no circulating immunoglobulin-bearing lymphocytes. Complement receptor-bearing lymphocytes were present in the peripheral blood, and circulating T lymphocyte numbers were within normal limits. She was anergic to a battery of skin test antigens, and her lymphocytes in vitro showed a selective unresponsiveness to CMV antigen while responding normally to phytohemagglutinin and streptokinase. The course of the encephalitis was progressive with quadriplegia, aphasia and coma developing within six months of onset of symptoms. This is the fifth reported case documenting an association between CMV infection and the syndrome of thymoma with immunoglobulin deficiency, but the first report of fatal CMV encephalitis in a patient with thymoma and immunoglobulin deficiency."}
{"id": "PMID:227267", "title": "Estrogen-binding proteins in the human postmenopausal uterus.", "content": "Two intracellular high-affinity, low-capacity estrogen-binding proteins, which have the characteristics of receptors, with equilibrium dissociation constants of 10(-10)M and 10(-9)M, have been observed in the human uterus. The higher-affinity protein (10(-10)M) appears to play the main role in activating end-organ response to estrogen stimulation. The role of the lower-affinity protein (10(-9)M) is uncertain. In a human postmenopausal uterine system without estrogen stimulation, Scatchard analysis of uterine cytosol partially purified by ammonium sulfate fractionation and incubated at 4 degrees C for 18 hours revealed only the higher-affinity receptor component (10(-10)M). In a post menopausal uterine system with estrogen priming (and in the premenopausal uterus) both the high- and low-affinity components were observed. Competition studies indicated that the receptors were specific for estradiol. The clinical significance of these findings is discussed.", "contents": "Estrogen-binding proteins in the human postmenopausal uterus. Two intracellular high-affinity, low-capacity estrogen-binding proteins, which have the characteristics of receptors, with equilibrium dissociation constants of 10(-10)M and 10(-9)M, have been observed in the human uterus. The higher-affinity protein (10(-10)M) appears to play the main role in activating end-organ response to estrogen stimulation. The role of the lower-affinity protein (10(-9)M) is uncertain. In a human postmenopausal uterine system without estrogen stimulation, Scatchard analysis of uterine cytosol partially purified by ammonium sulfate fractionation and incubated at 4 degrees C for 18 hours revealed only the higher-affinity receptor component (10(-10)M). In a post menopausal uterine system with estrogen priming (and in the premenopausal uterus) both the high- and low-affinity components were observed. Competition studies indicated that the receptors were specific for estradiol. The clinical significance of these findings is discussed."}
{"id": "PMID:227268", "title": "Stigma and state hospital patients.", "content": "This study set out to measure the degree of social stigma experienced by discharged mental hospital patients and the extent to which these patients were viewed as a burden by family and friends. Predictors of stigma included social class and demographic factors, posthospital situation, emotional functioning, and use of aftercare facilities. However, available measures were able to account for little of the variance in stigma, and further research is suggested to establish more reliable predictors of mental patient stigmatization.", "contents": "Stigma and state hospital patients. This study set out to measure the degree of social stigma experienced by discharged mental hospital patients and the extent to which these patients were viewed as a burden by family and friends. Predictors of stigma included social class and demographic factors, posthospital situation, emotional functioning, and use of aftercare facilities. However, available measures were able to account for little of the variance in stigma, and further research is suggested to establish more reliable predictors of mental patient stigmatization."}
{"id": "PMID:227269", "title": "Transport and metabolism of fructose in fat cells of normal and hypophysectomized rats.", "content": "We have shown earlier that the glucose carrier of fat cells of hypophysectomized rats operates at maximal speed in the basal state and that these cells are insensitive to insulin. Here we characterize fructose transport and metabolism in adipocytes of normal and hypophysectomized rats. 3-O-methylglucose inhibits insulin-stimulated incorporation of [U-14C]fructose into fat cells and has no significant effect on basal fructose metabolism. In contrast, 2-deoxyglucose inhibits both basal and insulin-stimulated fructose incorporation. Insulin enhances fructose incorporation in normal adipocytes only in the absence of 3-O-methylglucose. In hypophysectomized rats, incorporation of glucose and of fructose is decreased and insensitive to insulin. In contrast to the glucose carrier, the specific fructose carrier appears to be insensitive to insulin and to continue to operate with unchanged characteristics after hypophysectomy. Thus, hypophysectomy leads to a specific alteration of the insulin-sensitive glucose carrier, whereas the insulin-insensitive fructose carrier remains unaltered.", "contents": "Transport and metabolism of fructose in fat cells of normal and hypophysectomized rats. We have shown earlier that the glucose carrier of fat cells of hypophysectomized rats operates at maximal speed in the basal state and that these cells are insensitive to insulin. Here we characterize fructose transport and metabolism in adipocytes of normal and hypophysectomized rats. 3-O-methylglucose inhibits insulin-stimulated incorporation of [U-14C]fructose into fat cells and has no significant effect on basal fructose metabolism. In contrast, 2-deoxyglucose inhibits both basal and insulin-stimulated fructose incorporation. Insulin enhances fructose incorporation in normal adipocytes only in the absence of 3-O-methylglucose. In hypophysectomized rats, incorporation of glucose and of fructose is decreased and insensitive to insulin. In contrast to the glucose carrier, the specific fructose carrier appears to be insensitive to insulin and to continue to operate with unchanged characteristics after hypophysectomy. Thus, hypophysectomy leads to a specific alteration of the insulin-sensitive glucose carrier, whereas the insulin-insensitive fructose carrier remains unaltered."}
{"id": "PMID:227271", "title": "Possible role of cyclic GMP in stimulus-secretion coupling by salt gland of the duck.", "content": "Stimulation of salt galnd secretion in domestic ducks in vivo increased the cyclic GMP concentration of the tissue, but had no effect on cyclic AMP levels. Methacholine, which is known to stimulate sodium transport by the glands both in vivo and in vitro, stimulated ouabain-sensitive respiration in salt gland slices. Cyclic GMP stimulated ouabain-sensitive respiration to the same extent as methacholine. Guanylate cyclase stimulators, hydroxylamine and sodium azide, also stimulated ouabain-sensitive respiration. The stimulation of ouabain-sensitive respiration by methacholine was blocked either by atropine or by removal of calcium from the incubation medium. The stimulation of ouabain-sensitive respiration by cyclic GMP still occurred in the absence of calcium. The above observations seem to indicate that cyclic GMP acts as a tertiary link in the process of stimulus-secretion coupling in the tissue.", "contents": "Possible role of cyclic GMP in stimulus-secretion coupling by salt gland of the duck. Stimulation of salt galnd secretion in domestic ducks in vivo increased the cyclic GMP concentration of the tissue, but had no effect on cyclic AMP levels. Methacholine, which is known to stimulate sodium transport by the glands both in vivo and in vitro, stimulated ouabain-sensitive respiration in salt gland slices. Cyclic GMP stimulated ouabain-sensitive respiration to the same extent as methacholine. Guanylate cyclase stimulators, hydroxylamine and sodium azide, also stimulated ouabain-sensitive respiration. The stimulation of ouabain-sensitive respiration by methacholine was blocked either by atropine or by removal of calcium from the incubation medium. The stimulation of ouabain-sensitive respiration by cyclic GMP still occurred in the absence of calcium. The above observations seem to indicate that cyclic GMP acts as a tertiary link in the process of stimulus-secretion coupling in the tissue."}
{"id": "PMID:227272", "title": "Effect of Amytal on metabolism of perfused rat heart: relationship between glycolysis and oxidative phosphorylation.", "content": "In perfused rat hearts, infusion of increasing concentration of Amytal caused progressive inhibition of respiration and increase in glycolytic activity. At maximal inhibition of respiration, with glucose as the substrate, glycolysis provided about 60% of the total ATP produced. The myocardial content of ATP remained constant irrespective of the infused Amytal concentration but [CrP]/[Cr] and [ATP]/[ADP]f[Pi] progressively decreased. Changes in the concentrations of glycolytic intermediates were observed, the most pronounced of which were increases in fructose 1,6-diphosphate and lactate contents and a decrease in the pyruvate level. Myocardial levels of oxaloacetate, malate, and alanine were elevated and so was alanine release from the tissue. Substitution of glucose with pyruvate caused a large increase in the concentrations of the tricarboxylic acid cycle intermediates and consequent accumulation of reducing equivalents in the mitochrondria. With the latter substrate, in the presence of Amytal, the rates of mitochondrial ATP production were higher than those with glucose as the substrate. The metabolic picture of the Amytal block resembles biochemical manifestations of human myopathies of mitochondrial origin, and therefore Amytal inhibition is a convenient model system for exploration of intermediary metabolism in these defects.", "contents": "Effect of Amytal on metabolism of perfused rat heart: relationship between glycolysis and oxidative phosphorylation. In perfused rat hearts, infusion of increasing concentration of Amytal caused progressive inhibition of respiration and increase in glycolytic activity. At maximal inhibition of respiration, with glucose as the substrate, glycolysis provided about 60% of the total ATP produced. The myocardial content of ATP remained constant irrespective of the infused Amytal concentration but [CrP]/[Cr] and [ATP]/[ADP]f[Pi] progressively decreased. Changes in the concentrations of glycolytic intermediates were observed, the most pronounced of which were increases in fructose 1,6-diphosphate and lactate contents and a decrease in the pyruvate level. Myocardial levels of oxaloacetate, malate, and alanine were elevated and so was alanine release from the tissue. Substitution of glucose with pyruvate caused a large increase in the concentrations of the tricarboxylic acid cycle intermediates and consequent accumulation of reducing equivalents in the mitochrondria. With the latter substrate, in the presence of Amytal, the rates of mitochondrial ATP production were higher than those with glucose as the substrate. The metabolic picture of the Amytal block resembles biochemical manifestations of human myopathies of mitochondrial origin, and therefore Amytal inhibition is a convenient model system for exploration of intermediary metabolism in these defects."}
{"id": "PMID:227273", "title": "Role of Ca in isoproterenol-induced increases in cAMP levels in rat uterus.", "content": "The influence of alteration in the Ca2+ environment of the tissue on isoproterenol-induced increases in cAMP levels and relaxation was studied in rat uterus. In muscles depolarized with 47.5 mM K+ (with or without Na+), the ability of isoproterenol to increase cAMP levels and to produce relaxation was found to be inversely related to external calcium concentration. The pretreatment of the muscle with D600 or EGTA restored the cAMP response to isoproterenol in the depolarized uterus to a level observed in nondepolarized muscle. The study with Ro 20-1724, a phosphodiesterase (PDE) inhibitor indicated that the failure of isoproterenol to elevate cAMP levels in the depolarized uterus could not be related to the activation of PDE by Ca2+. The exposure of rat uterus to a zero-Ca2+ solution accentuated the increases in cAMP levels produced by isoproterenol. These results have raised the question of a possible regulatory role of Ca2+ in beta-adrenoceptor-induced increases in cAMP levels in uterine smooth muscle.", "contents": "Role of Ca in isoproterenol-induced increases in cAMP levels in rat uterus. The influence of alteration in the Ca2+ environment of the tissue on isoproterenol-induced increases in cAMP levels and relaxation was studied in rat uterus. In muscles depolarized with 47.5 mM K+ (with or without Na+), the ability of isoproterenol to increase cAMP levels and to produce relaxation was found to be inversely related to external calcium concentration. The pretreatment of the muscle with D600 or EGTA restored the cAMP response to isoproterenol in the depolarized uterus to a level observed in nondepolarized muscle. The study with Ro 20-1724, a phosphodiesterase (PDE) inhibitor indicated that the failure of isoproterenol to elevate cAMP levels in the depolarized uterus could not be related to the activation of PDE by Ca2+. The exposure of rat uterus to a zero-Ca2+ solution accentuated the increases in cAMP levels produced by isoproterenol. These results have raised the question of a possible regulatory role of Ca2+ in beta-adrenoceptor-induced increases in cAMP levels in uterine smooth muscle."}
{"id": "PMID:227274", "title": "Hyperglucagonemia and alpha-adrenergic receptor in acute hypoxia.", "content": "The plasma immunoreactive glucagon (IRG) response to hypoxia was studied in puppies. Three groups of paired experiments were performed. In group I, 8% O2:92% N2 ventilation (PaO2 20--30 torr) produced a rise in plasma IRG and glucose as well as hypotension and bradycardia. However, when group I was air ventilated (PaO2 greater than 70 torr) and given glucose infusions producing hyperglycemia of similar degree, plasma IRG was unchanged. Group II received alpha-adrenergic blockade (phenoxybenzamine). When made hypoxic, group II developed no significant IRG rise and less hyperglycemia than with hypoxia alone. Hypotension was more severe with hypoxia plus alpha-blockade. Phenoxybenzamine itself did not change plasma IRG or glucose during air breathing. Group III receivi developed hyperglucagonemia and hyperglycemia not significantly different from that with hypoxia alone. However, hypoxia-caused hypotension and bradycardia was more pronounced with beta-blockade. No change in plasma IRG or glucose occurred in group III animals breathing air. These data suggest that a) glucagon release is caused by acute oxygen deficiency, and b) the hypoxic response is largely adrenergically mediated with the major role played by the alpha-receptor.", "contents": "Hyperglucagonemia and alpha-adrenergic receptor in acute hypoxia. The plasma immunoreactive glucagon (IRG) response to hypoxia was studied in puppies. Three groups of paired experiments were performed. In group I, 8% O2:92% N2 ventilation (PaO2 20--30 torr) produced a rise in plasma IRG and glucose as well as hypotension and bradycardia. However, when group I was air ventilated (PaO2 greater than 70 torr) and given glucose infusions producing hyperglycemia of similar degree, plasma IRG was unchanged. Group II received alpha-adrenergic blockade (phenoxybenzamine). When made hypoxic, group II developed no significant IRG rise and less hyperglycemia than with hypoxia alone. Hypotension was more severe with hypoxia plus alpha-blockade. Phenoxybenzamine itself did not change plasma IRG or glucose during air breathing. Group III receivi developed hyperglucagonemia and hyperglycemia not significantly different from that with hypoxia alone. However, hypoxia-caused hypotension and bradycardia was more pronounced with beta-blockade. No change in plasma IRG or glucose occurred in group III animals breathing air. These data suggest that a) glucagon release is caused by acute oxygen deficiency, and b) the hypoxic response is largely adrenergically mediated with the major role played by the alpha-receptor."}
{"id": "PMID:227276", "title": "Actions of histamine, secretin, and PGE2 on cyclic AMP production by isolated canine fundic mucosal cells.", "content": "Cyclic AMP production was studied in isolated canine fundic gastric mucosal cells. Histamine, prostaglandin E2 (PGE2), and secretin increased cyclic AMP production by unenriched mucosal cells. In separated cell fractions, histamine stimulation of cyclic AMP production correlated with the parietal cell content of the fractions. Secretin in concentrations above 1 nM stimulated cyclic AMP production, and this effect correlated with the pepsinogen content of the separated cell fractions. At concentrations above 1 microM, PGE2 stimulated cyclic AMP production; this effect was found in all separated cell fractions and was not associated with any of the available cell markers. PGE2 stimulation of cyclic AMP production was, however, negatively correlated with the parietal cell content. Thus, histamine stimulated cyclic AMP production by parietal cells and secretin stimulated production of cyclic AMP by chief cells. PGE2 stimulation of cyclic AMP production could not be localized to a single cell type but occurred primarily in nonparietal cells.", "contents": "Actions of histamine, secretin, and PGE2 on cyclic AMP production by isolated canine fundic mucosal cells. Cyclic AMP production was studied in isolated canine fundic gastric mucosal cells. Histamine, prostaglandin E2 (PGE2), and secretin increased cyclic AMP production by unenriched mucosal cells. In separated cell fractions, histamine stimulation of cyclic AMP production correlated with the parietal cell content of the fractions. Secretin in concentrations above 1 nM stimulated cyclic AMP production, and this effect correlated with the pepsinogen content of the separated cell fractions. At concentrations above 1 microM, PGE2 stimulated cyclic AMP production; this effect was found in all separated cell fractions and was not associated with any of the available cell markers. PGE2 stimulation of cyclic AMP production was, however, negatively correlated with the parietal cell content. Thus, histamine stimulated cyclic AMP production by parietal cells and secretin stimulated production of cyclic AMP by chief cells. PGE2 stimulation of cyclic AMP production could not be localized to a single cell type but occurred primarily in nonparietal cells."}
{"id": "PMID:227278", "title": "Effect of sodium restriction on plasma renin activity and renin granules in rat kidney.", "content": "The present study was carried out to procure detailed information on the relationship between chronic sodium restriction and renin content of kidneys at a subcellular level in the rat. Renin granules (RG) were separated by a discontinuous sucrose-density gradient (from 1.2 to 1.7 M) centrifugation. In control rats, RG were mainly recovered in the fractions corresponding to 1.5 M sucrose, whereas most of the mitochondria, lysosomes, and microsomes equilibrated in upper fractions. The RG fraction contained approximately 60% of total granular renin activity. Low sodium intake for 4 wk resulted in a 12.4-fold increase in plasma renin activity and led to a 2.6-fold increase in renin activity of the RG fraction. But in sodium-restricted rats there was no alteration in the distribution pattern of renin activity on sucrose-density gradients, indicating that there was no change in the density of RG. These results provide evidence for increased renin activity in storage granules following chronic sodium restriction.", "contents": "Effect of sodium restriction on plasma renin activity and renin granules in rat kidney. The present study was carried out to procure detailed information on the relationship between chronic sodium restriction and renin content of kidneys at a subcellular level in the rat. Renin granules (RG) were separated by a discontinuous sucrose-density gradient (from 1.2 to 1.7 M) centrifugation. In control rats, RG were mainly recovered in the fractions corresponding to 1.5 M sucrose, whereas most of the mitochondria, lysosomes, and microsomes equilibrated in upper fractions. The RG fraction contained approximately 60% of total granular renin activity. Low sodium intake for 4 wk resulted in a 12.4-fold increase in plasma renin activity and led to a 2.6-fold increase in renin activity of the RG fraction. But in sodium-restricted rats there was no alteration in the distribution pattern of renin activity on sucrose-density gradients, indicating that there was no change in the density of RG. These results provide evidence for increased renin activity in storage granules following chronic sodium restriction."}
{"id": "PMID:227280", "title": "Metabolism of totally ischemic excised dog heart. II. Interpretation of a computer model.", "content": "Analysis of the ischemic dog heart preparation described in the preceding paper indicates that it is an analogue in slow motion of the tissue in the center of a cardiac infarct. It is respiring very slowly and not capable of performing mechanical work. Glycolysis starts up with both glucose and glycogen as inputs. Later hexokinase and to some extent phosphofructokinase become limiting owing to inhibitor accumulation or acidosis. Metabolism then results primarily from cAMP-driven glycogenolysis, largely limited by the glycogen debranching enzymes at later times, with accumultion not only of lactate and alpha-glycerophosphate but of glucose as well. Amino acid levels oscillate with time while fatty acids accumulate at late times. The elevation of cAMP at later times may involve disturbances in its metabolism as well as mechanisms such as adenosine accumulation that are more important in cardiac ischemia than in normal heart. The clinical implications of this behavior are discussed.", "contents": "Metabolism of totally ischemic excised dog heart. II. Interpretation of a computer model. Analysis of the ischemic dog heart preparation described in the preceding paper indicates that it is an analogue in slow motion of the tissue in the center of a cardiac infarct. It is respiring very slowly and not capable of performing mechanical work. Glycolysis starts up with both glucose and glycogen as inputs. Later hexokinase and to some extent phosphofructokinase become limiting owing to inhibitor accumulation or acidosis. Metabolism then results primarily from cAMP-driven glycogenolysis, largely limited by the glycogen debranching enzymes at later times, with accumultion not only of lactate and alpha-glycerophosphate but of glucose as well. Amino acid levels oscillate with time while fatty acids accumulate at late times. The elevation of cAMP at later times may involve disturbances in its metabolism as well as mechanisms such as adenosine accumulation that are more important in cardiac ischemia than in normal heart. The clinical implications of this behavior are discussed."}
{"id": "PMID:227281", "title": "REM architecture changes in bipolar and unipolar depression.", "content": "The authors compared total night sleep measures and REM sleep architecture values for normal control subjects (N = 36), unipolar depressed patients (N = 36), and bipolar depressed patients (N = 22). The unipolar and bipolar patients had significantly greater fragmentation of REM periods than control subjects, and bipolar patients showed greater fragmentation of REM periods than unipolar patients. In both the unipolar and bipolar samples, the duration of successive REM periods was related to the total number of REM periods during sleep.", "contents": "REM architecture changes in bipolar and unipolar depression. The authors compared total night sleep measures and REM sleep architecture values for normal control subjects (N = 36), unipolar depressed patients (N = 36), and bipolar depressed patients (N = 22). The unipolar and bipolar patients had significantly greater fragmentation of REM periods than control subjects, and bipolar patients showed greater fragmentation of REM periods than unipolar patients. In both the unipolar and bipolar samples, the duration of successive REM periods was related to the total number of REM periods during sleep."}
{"id": "PMID:227282", "title": "Prognosis after resection of metachronous multiple bronchogenic carcinoma.", "content": "Information on 55 cases of multiple metachronous lung cancer in which both tumors were resected was collected from published reports for comparison with a series of 214 single cancer cases treated by lobectomy in Philadelphia teaching hospitals. The two groups were similar with respect to age, extent of resection, and histologic type of cancer (the second lesion in the multiple cancer group). The life table method was used to assess survival in the multiple cancer group for 4 years after the second resection. Survival in the two groups was similar in the first 2 years, but at the end of the third and fourth years the survival rate for the multiple cancer group was only half that of the single cancer group. These differences were statistically significant. Prognosis 4 years after resection of a second metachronous bronchogenic carcinoma is poor.", "contents": "Prognosis after resection of metachronous multiple bronchogenic carcinoma. Information on 55 cases of multiple metachronous lung cancer in which both tumors were resected was collected from published reports for comparison with a series of 214 single cancer cases treated by lobectomy in Philadelphia teaching hospitals. The two groups were similar with respect to age, extent of resection, and histologic type of cancer (the second lesion in the multiple cancer group). The life table method was used to assess survival in the multiple cancer group for 4 years after the second resection. Survival in the two groups was similar in the first 2 years, but at the end of the third and fourth years the survival rate for the multiple cancer group was only half that of the single cancer group. These differences were statistically significant. Prognosis 4 years after resection of a second metachronous bronchogenic carcinoma is poor."}
{"id": "PMID:227283", "title": "Sleep in herniorrhaphy patients.", "content": "The nocturnal sleep patterns of 10 elective herniorrhaphy patients were documented by continuous, 8 hour polygraphic recordings from night 1 of hospitalization until discharge on day 4 or 5. Subjects showed a dramatic loss of REM sleep and stages III and IV and major increases in time awake and drowsy for the first 2 postoperative nights, with a gradual return toward normal sleep over the hospitalization period. The significance for healing of the loss of stages REM, III, and IV is discussed, especially with regard to hospital procedures and the use of medications.", "contents": "Sleep in herniorrhaphy patients. The nocturnal sleep patterns of 10 elective herniorrhaphy patients were documented by continuous, 8 hour polygraphic recordings from night 1 of hospitalization until discharge on day 4 or 5. Subjects showed a dramatic loss of REM sleep and stages III and IV and major increases in time awake and drowsy for the first 2 postoperative nights, with a gradual return toward normal sleep over the hospitalization period. The significance for healing of the loss of stages REM, III, and IV is discussed, especially with regard to hospital procedures and the use of medications."}
{"id": "PMID:227297", "title": "[Bronchial granular cell tumor. Apropos of 2 cases].", "content": "The authors report two new cases of bronchial granular cell tumour, a site which remains relatively rare. One of these cases was studied from the point of view of histoenzymology and ultrastructure. The appearances seen were identical to those seen in the literature. They lead to the problem of the histogenetics of the lesion, various morphological factors favouring a Schwann cell origin, whilst the presence of \"transitional\" cells is more in favour of a mesenchymatous origin, or at least the role of mesenchymatous cells in the development of these lesions.", "contents": "[Bronchial granular cell tumor. Apropos of 2 cases]. The authors report two new cases of bronchial granular cell tumour, a site which remains relatively rare. One of these cases was studied from the point of view of histoenzymology and ultrastructure. The appearances seen were identical to those seen in the literature. They lead to the problem of the histogenetics of the lesion, various morphological factors favouring a Schwann cell origin, whilst the presence of \"transitional\" cells is more in favour of a mesenchymatous origin, or at least the role of mesenchymatous cells in the development of these lesions."}
{"id": "PMID:227299", "title": "Live cytomegalovirus vaccination of renal transplant candidates. A preliminary trial.", "content": "Significant morbidity and mortality are associated with primary cytomegalovirus infections in renal-transplant recipients. In the hope that immunity to cytomegalovirus could safely be established before transplantation, we vaccinated 12 seronegative renal-transplant candidates with the Towne 125 strain of live human cytomegalovirus. Before transplantation, there were no significant reactions except for erythema and induration at the site of inoculation. All vaccinees seroconverted, and the three patients tested acquired a cytomegalovirus-specific cellular immune response. Ten vaccinees underwent transplantation: Nine have completed at least 3 months of follow-up, and eight retain functioning allografts up to 1 year later. Although cytomegalovirus was isolated from six patients after transplantation, the restriction endonuclease patterns of the viral DNA of four of these isolates differed significantly from those of the vaccine strain. Therefore, it appears that the vaccine strain did not become latent in the host, at least in a form that could be reactivated.", "contents": "Live cytomegalovirus vaccination of renal transplant candidates. A preliminary trial. Significant morbidity and mortality are associated with primary cytomegalovirus infections in renal-transplant recipients. In the hope that immunity to cytomegalovirus could safely be established before transplantation, we vaccinated 12 seronegative renal-transplant candidates with the Towne 125 strain of live human cytomegalovirus. Before transplantation, there were no significant reactions except for erythema and induration at the site of inoculation. All vaccinees seroconverted, and the three patients tested acquired a cytomegalovirus-specific cellular immune response. Ten vaccinees underwent transplantation: Nine have completed at least 3 months of follow-up, and eight retain functioning allografts up to 1 year later. Although cytomegalovirus was isolated from six patients after transplantation, the restriction endonuclease patterns of the viral DNA of four of these isolates differed significantly from those of the vaccine strain. Therefore, it appears that the vaccine strain did not become latent in the host, at least in a form that could be reactivated."}
{"id": "PMID:227296", "title": "Possible alpha-adrenergic involvement in nicotine induced alteration of spermatogenesis in rat.", "content": "Nicotine caused a fall in primary spermatocyte number together with a retardation of spermatocyte to spermatid conversions process. These effects of nicotine were possibly secondary to increased activity of adrenomedullary catecholamines, since the antispermatogenic effect of nicotine was prevented by phentolamine, a known blocker of catecholamine action at the alpha-receptor level.", "contents": "Possible alpha-adrenergic involvement in nicotine induced alteration of spermatogenesis in rat. Nicotine caused a fall in primary spermatocyte number together with a retardation of spermatocyte to spermatid conversions process. These effects of nicotine were possibly secondary to increased activity of adrenomedullary catecholamines, since the antispermatogenic effect of nicotine was prevented by phentolamine, a known blocker of catecholamine action at the alpha-receptor level."}
{"id": "PMID:227300", "title": "Asymptomatic glomerulonephritis after nonstreptococcal upper respiratory infections.", "content": "Two hundred forty previously healthy military personnel with nonstreptococcal upper respiratory infections were prospectively studied to define the incidence and clinicopathologic characteristics of possible virus-associated glomerulonephritis. Nine patients without preceding streptococcal infection had erythrocyte casts on urinalysis and glomerulonephritis on biopsy. Of these nine, four had a reduction in total hemolytic complement and five had serologic evidence of infection with adenovirus, influenza A, or influenza B. Initial renal biopsy showed either focal or diffuse mesangial proliferation in all nine, with mesangial C3 deposits in six specimens. Repeat biopsy in three showed histologic improvement or loss of immunofluorescent staining, or both. Sequential creatinine clearances were reduced to 74 to 90 mL/min.1.73 m2 in five patients for the duration of follow-up. We conclude that nonstreptococcal upper respiratory infection is frequently associated with glomerulonephritis and that abnormal glomerular structure and decreased creatinine clearances may persist for at least 2 to 8 months.", "contents": "Asymptomatic glomerulonephritis after nonstreptococcal upper respiratory infections. Two hundred forty previously healthy military personnel with nonstreptococcal upper respiratory infections were prospectively studied to define the incidence and clinicopathologic characteristics of possible virus-associated glomerulonephritis. Nine patients without preceding streptococcal infection had erythrocyte casts on urinalysis and glomerulonephritis on biopsy. Of these nine, four had a reduction in total hemolytic complement and five had serologic evidence of infection with adenovirus, influenza A, or influenza B. Initial renal biopsy showed either focal or diffuse mesangial proliferation in all nine, with mesangial C3 deposits in six specimens. Repeat biopsy in three showed histologic improvement or loss of immunofluorescent staining, or both. Sequential creatinine clearances were reduced to 74 to 90 mL/min.1.73 m2 in five patients for the duration of follow-up. We conclude that nonstreptococcal upper respiratory infection is frequently associated with glomerulonephritis and that abnormal glomerular structure and decreased creatinine clearances may persist for at least 2 to 8 months."}
{"id": "PMID:227305", "title": "Serotoninergic involvement in the regulation of circadian rhythms of hypothalamic-pituitary adrenal and prolactin axis.", "content": "A detailed review of their own experiments and of data existing in the literature regarding the role played by 5HT in the control of circadian rhythms of HHAA and HHPA is given by the AA. In rats, a positive correlation between 5-HT content in the limbic system and plasma corticosterone circadian rhythm has been shown to exist by means of pharmacological and neurosurgical approaches. Lesions of the raphe area result in an abolition of diurnal periodicity of plasma steroids similar to that obtained after inhibition of 5-HT synthesis by means of PCPA. A modification of the amplitude of the plasma corticosterone circadian variations also occurs after more selective destruction of some nuclei (n. centralis superior and n. raphe dorsalis) which reduced 5-HT concentration both in the hypothalamus and the hippocampus. Isolation of the mediobasal hypothalamus by a frontal cut posterior to the optic chiasma abolishes the diurnal fluctuation of plasma corticosterone, indicating that the suprachiasmatic nucleus is a focal site for the 5-HT regulation of the phasic activity of the HHAA. Evidence in favour of 5-HT mechanisms in the limbic area as the biological clock regulating the circadian variations of the adrenal axis is also provided. Restoration of the diurnal rhythm of plasma corticosterone after its abolition could be explained with the existence of a small functional pool of brain 5-HT or with the development of receptor supersensitivity. Pharmacological and surgical manipulation on central 5-HT neurons suggest the existence of two distinct serotoninergic mechanisms, a limbic one and an intrahypothalamic one, which play a modulatory role in the circadian variations of plasma PRL. Also in this case, adaptive accessory brain structures can take over in restoring the circadian hormones periodicity in conditions of impairment of the main serotoninergic mechanisms.", "contents": "Serotoninergic involvement in the regulation of circadian rhythms of hypothalamic-pituitary adrenal and prolactin axis. A detailed review of their own experiments and of data existing in the literature regarding the role played by 5HT in the control of circadian rhythms of HHAA and HHPA is given by the AA. In rats, a positive correlation between 5-HT content in the limbic system and plasma corticosterone circadian rhythm has been shown to exist by means of pharmacological and neurosurgical approaches. Lesions of the raphe area result in an abolition of diurnal periodicity of plasma steroids similar to that obtained after inhibition of 5-HT synthesis by means of PCPA. A modification of the amplitude of the plasma corticosterone circadian variations also occurs after more selective destruction of some nuclei (n. centralis superior and n. raphe dorsalis) which reduced 5-HT concentration both in the hypothalamus and the hippocampus. Isolation of the mediobasal hypothalamus by a frontal cut posterior to the optic chiasma abolishes the diurnal fluctuation of plasma corticosterone, indicating that the suprachiasmatic nucleus is a focal site for the 5-HT regulation of the phasic activity of the HHAA. Evidence in favour of 5-HT mechanisms in the limbic area as the biological clock regulating the circadian variations of the adrenal axis is also provided. Restoration of the diurnal rhythm of plasma corticosterone after its abolition could be explained with the existence of a small functional pool of brain 5-HT or with the development of receptor supersensitivity. Pharmacological and surgical manipulation on central 5-HT neurons suggest the existence of two distinct serotoninergic mechanisms, a limbic one and an intrahypothalamic one, which play a modulatory role in the circadian variations of plasma PRL. Also in this case, adaptive accessory brain structures can take over in restoring the circadian hormones periodicity in conditions of impairment of the main serotoninergic mechanisms."}
{"id": "PMID:227306", "title": "The participation of monoaminergic central mechanisms on adenohypophyseal secretion.", "content": "In acute and chronic experiments in rats has been studied the action of drugs influencing central neuro-transmitter on the functional activity of hypophysis-adrenal and hypophysis-gonadal system. Evidence has been obtained that central neurotransmitters participate in the control of ACTH-glucocorticoids secretion. However, there is no clear correlation between noradrenaline and serotonin level in the brain and the degree of reaction of pituitary-adrenal complex to stimuli. Pharmacological analysis of nervous regulation of gonadotropic hypophysis function has revealed the significance of adrenergic mediation in the mechanism of feedback action of sex hormones and in the mechanism of limbic influences on hypothalamic regulation of gonadotropin secretion.", "contents": "The participation of monoaminergic central mechanisms on adenohypophyseal secretion. In acute and chronic experiments in rats has been studied the action of drugs influencing central neuro-transmitter on the functional activity of hypophysis-adrenal and hypophysis-gonadal system. Evidence has been obtained that central neurotransmitters participate in the control of ACTH-glucocorticoids secretion. However, there is no clear correlation between noradrenaline and serotonin level in the brain and the degree of reaction of pituitary-adrenal complex to stimuli. Pharmacological analysis of nervous regulation of gonadotropic hypophysis function has revealed the significance of adrenergic mediation in the mechanism of feedback action of sex hormones and in the mechanism of limbic influences on hypothalamic regulation of gonadotropin secretion."}
{"id": "PMID:227307", "title": "Effect of drugs with addicting properties on brain catecholamines.", "content": "The effect of morphine and amobarbital on catecholamine metabolism in different regions of the rat brain (cortex, hippocampus, striatum, hypothalamus and midbrain) was studied. The investigation showed that drugs of different chemical structures but with common addicting properties evoke the same type of changes in catecholamine metabolism which are expressed by an intensification of release and disintegration of norepinephrine and by a decrease in dopamine level.", "contents": "Effect of drugs with addicting properties on brain catecholamines. The effect of morphine and amobarbital on catecholamine metabolism in different regions of the rat brain (cortex, hippocampus, striatum, hypothalamus and midbrain) was studied. The investigation showed that drugs of different chemical structures but with common addicting properties evoke the same type of changes in catecholamine metabolism which are expressed by an intensification of release and disintegration of norepinephrine and by a decrease in dopamine level."}
{"id": "PMID:227308", "title": "Release of dopamine from striatal synaptosomes.", "content": "The mechanisms of dopamine (DA) release central nerve endings have been investigated utilizing superfused rat striatal synaptosomes. Nomifensine was selected as a tool to discriminate between release mediated by the DA carrier and release occurring independently of the carrier. The following conclusions can be drawn from the results obtained: 1) Alterations of the sodium gradient across the synaptosomal membrane, induced by omission of extracellular Na+ or by ouabain, enhanced the release of 3H-DA from prelabeled synaptosomes. The release was blocked by nomifensine and therefore it was carrier-mediated. 2) The release of DA elicited by amphetamine and related phenylethylamines was nomifensine-sensitive, suggesting that the released DA existed from synaptosomes through the membrane carrier. 3) Depolarization of synaptosomes by high K+ triggered the release of both \"newly taken up\" and \"newly synthesized\" DA. 4) The calcium-dependent release of DA (induced by high K+, veratridine of by the ionophore A23187) was not affected by the carrier blocker nomifensine and may occur by an exocytic-like process. 5) The effects of apomorphine and neuroleptics on the stimulus-evoked release of DA do not support the existence of a presynaptic receptor-mediated inhibitory control of DA release identical to that described for noradrenaline.", "contents": "Release of dopamine from striatal synaptosomes. The mechanisms of dopamine (DA) release central nerve endings have been investigated utilizing superfused rat striatal synaptosomes. Nomifensine was selected as a tool to discriminate between release mediated by the DA carrier and release occurring independently of the carrier. The following conclusions can be drawn from the results obtained: 1) Alterations of the sodium gradient across the synaptosomal membrane, induced by omission of extracellular Na+ or by ouabain, enhanced the release of 3H-DA from prelabeled synaptosomes. The release was blocked by nomifensine and therefore it was carrier-mediated. 2) The release of DA elicited by amphetamine and related phenylethylamines was nomifensine-sensitive, suggesting that the released DA existed from synaptosomes through the membrane carrier. 3) Depolarization of synaptosomes by high K+ triggered the release of both \"newly taken up\" and \"newly synthesized\" DA. 4) The calcium-dependent release of DA (induced by high K+, veratridine of by the ionophore A23187) was not affected by the carrier blocker nomifensine and may occur by an exocytic-like process. 5) The effects of apomorphine and neuroleptics on the stimulus-evoked release of DA do not support the existence of a presynaptic receptor-mediated inhibitory control of DA release identical to that described for noradrenaline."}
{"id": "PMID:227310", "title": "[Isolated trigeminal neuropathy revealing the presence of Sharp's syndrome or MCTD (mixed connective tissue disease) (author's transl)].", "content": "Isolated neuropathies of 5th cranial nerves are rare apart from primary facial neuralgia. A case is reported, in which Raynaud's syndrome was also present, that enabled a diagnosis of mixed connective tissue disease to be established. The authors underline the importance of undertaking complete immunological investigations in order to decide whether there is a particular type of systemic disease present, which could be responsible for these special types of trigeminal nerve disorders.", "contents": "[Isolated trigeminal neuropathy revealing the presence of Sharp's syndrome or MCTD (mixed connective tissue disease) (author's transl)]. Isolated neuropathies of 5th cranial nerves are rare apart from primary facial neuralgia. A case is reported, in which Raynaud's syndrome was also present, that enabled a diagnosis of mixed connective tissue disease to be established. The authors underline the importance of undertaking complete immunological investigations in order to decide whether there is a particular type of systemic disease present, which could be responsible for these special types of trigeminal nerve disorders."}
{"id": "PMID:227315", "title": "Plasma lipids on chronic uraemic and transplantation patients.", "content": "We studied the concentrations of total cholesterol, HDL-cholesterol and triglyceride in the plasma in renal (n = 48) patients. In undialyzed uraemic patients (mean serum creatinine value 439 mumol/l) the plasma cholesterol level was somewhat higher (6.47 mmol/l) than in the control (n = 27) group (5.67 mmol/l). HCL-cholesterol was lower (1.02 mmol/l vs 1.49 mmol/l) and the triglycerides higher (2.07 mmol/l vs 1.07 mmol/l) than in the control group. In dialyzed patients the cholesterol level (5.88 mmol/l) was lower but the triglyceride level higher (2.58 mmol/l) than in undialyzed patients. Renal transplantation corrected the lipid variables to a certain degree (plasma cholesterol 5.55 mmol/l, plasma HDL-cholesterol 1.27 mmol/1 plasma triglycerides 1.15 mmol/l) but HDL-cholesterol remained still somewhat lower than in the control group. No \"critical level\" of renal function at which the changes of lipoprotein metabolism arise, could be demonstrated, and it seems that e.g. HDL-cholesterol is low already when the diagnosis of renal insufficiency is made.", "contents": "Plasma lipids on chronic uraemic and transplantation patients. We studied the concentrations of total cholesterol, HDL-cholesterol and triglyceride in the plasma in renal (n = 48) patients. In undialyzed uraemic patients (mean serum creatinine value 439 mumol/l) the plasma cholesterol level was somewhat higher (6.47 mmol/l) than in the control (n = 27) group (5.67 mmol/l). HCL-cholesterol was lower (1.02 mmol/l vs 1.49 mmol/l) and the triglycerides higher (2.07 mmol/l vs 1.07 mmol/l) than in the control group. In dialyzed patients the cholesterol level (5.88 mmol/l) was lower but the triglyceride level higher (2.58 mmol/l) than in undialyzed patients. Renal transplantation corrected the lipid variables to a certain degree (plasma cholesterol 5.55 mmol/l, plasma HDL-cholesterol 1.27 mmol/1 plasma triglycerides 1.15 mmol/l) but HDL-cholesterol remained still somewhat lower than in the control group. No \"critical level\" of renal function at which the changes of lipoprotein metabolism arise, could be demonstrated, and it seems that e.g. HDL-cholesterol is low already when the diagnosis of renal insufficiency is made."}
{"id": "PMID:227316", "title": "[Role of hormone receptors in the regulation of the corpus luteum].", "content": "Recent publication dealing with the hormonal regulation of the corpus luteum function has been reviewed. Hormones and receptors involved in this regulation are: LH and placental analogue HCG, prolactin and placental analogue hPL, prostaglandins, oestradiol and androgens. The hormone receptor interaction, in the luteal cells, and the role of each hormone in the modulation of the cell responsiveness has been reviewed.", "contents": "[Role of hormone receptors in the regulation of the corpus luteum]. Recent publication dealing with the hormonal regulation of the corpus luteum function has been reviewed. Hormones and receptors involved in this regulation are: LH and placental analogue HCG, prolactin and placental analogue hPL, prostaglandins, oestradiol and androgens. The hormone receptor interaction, in the luteal cells, and the role of each hormone in the modulation of the cell responsiveness has been reviewed."}
{"id": "PMID:227317", "title": "[Biochemical investigations and trisomy 21 (author's transl)].", "content": "A general consideration of the pathogenesis of the various metabolic diseases which produce mental deficiency suggests that perturbation of the one carbon (folate) cycle may be important. Secondly, a review of diseases having some symptoms in common with trisomy 21 suggests the evidence of : a collagen disturbance (hypothyroidism and iminodipeptidurial) ; an oxygen disturbance (hypothyroidism and hemoglobinopathies) ; a cholinergic distrubance (Alzheimer's disease) ; a one-carbon-cycle disturbance (Lesch-Nyhan's disease). Thirdly, the peculiar pathology of trisomy 21 allows to find also a cholinergic disturbance and a disturbance close to the 10 formyl-tetrahydrololate entry of the folate cycle. Finally, an analysis of the possible effect of the excess of superoxide dismutase A and of the increase of glutathion peroxidase leads to the suspicion that a difficulty exists of dioxygenations and of non aromatic hydroxilations with a relative retardation of some FAD requiring reactions. A simplified scheme shows that these metabolic deviations could provoke a disturbance of the collagen and of synthesis of chemical mediators, in accordance with the indications furnished by the compared pathogenesis of the various affections studied. These heuristic reflexions open the way to further investigations.", "contents": "[Biochemical investigations and trisomy 21 (author's transl)]. A general consideration of the pathogenesis of the various metabolic diseases which produce mental deficiency suggests that perturbation of the one carbon (folate) cycle may be important. Secondly, a review of diseases having some symptoms in common with trisomy 21 suggests the evidence of : a collagen disturbance (hypothyroidism and iminodipeptidurial) ; an oxygen disturbance (hypothyroidism and hemoglobinopathies) ; a cholinergic distrubance (Alzheimer's disease) ; a one-carbon-cycle disturbance (Lesch-Nyhan's disease). Thirdly, the peculiar pathology of trisomy 21 allows to find also a cholinergic disturbance and a disturbance close to the 10 formyl-tetrahydrololate entry of the folate cycle. Finally, an analysis of the possible effect of the excess of superoxide dismutase A and of the increase of glutathion peroxidase leads to the suspicion that a difficulty exists of dioxygenations and of non aromatic hydroxilations with a relative retardation of some FAD requiring reactions. A simplified scheme shows that these metabolic deviations could provoke a disturbance of the collagen and of synthesis of chemical mediators, in accordance with the indications furnished by the compared pathogenesis of the various affections studied. These heuristic reflexions open the way to further investigations."}
{"id": "PMID:227314", "title": "Bone resorption in chronic otitis media.", "content": "Bone resorption is an important aspect of chronic otitis media contributing to many complications of this disease. It is postulated that the mechanism of this localized destructive process is chemical in origin. Collagenase, lysosomal enzymes, prostaglandins, and other cell mediators are thought to induce bone resorption, but the site of action and cellular origin of these substances remains unclear. In this report, we demonstrate the location and attempt to delineate the cellular origin of two enzymes, collagenase and the lysosomal enzyme acid phosphatase in guinea pig temporal bones and human ossicles from ears containing chronic otitis media. Tissue localization of these enzymes identifies sites of active bone resorption and demonstrates the cells initiating this process. Using immunohistochemical and immunocytochemical techniques, collagenase was seen surrounding mononuclear inflammatory cells of granulation tissue at bone resorbing margins and at the periphery of osteocyte lacunae adjacent to resorbing areas. Electron microscopic data suggests that collagenase is an extracellular enzyme foun at the periphery of osteocytes. In addition, abundant acid phosphatase activity was seen in the same cells that exhibited collagenase staining, lending credence to the destructive function of these cells. The chronic inflammatory reaction found in chronic otitis media appears to activate bone destruction through the dynamic activity of mononuclear inflammatory cells and stimulates bone cells to increase their destructive biochemical functions.", "contents": "Bone resorption in chronic otitis media. Bone resorption is an important aspect of chronic otitis media contributing to many complications of this disease. It is postulated that the mechanism of this localized destructive process is chemical in origin. Collagenase, lysosomal enzymes, prostaglandins, and other cell mediators are thought to induce bone resorption, but the site of action and cellular origin of these substances remains unclear. In this report, we demonstrate the location and attempt to delineate the cellular origin of two enzymes, collagenase and the lysosomal enzyme acid phosphatase in guinea pig temporal bones and human ossicles from ears containing chronic otitis media. Tissue localization of these enzymes identifies sites of active bone resorption and demonstrates the cells initiating this process. Using immunohistochemical and immunocytochemical techniques, collagenase was seen surrounding mononuclear inflammatory cells of granulation tissue at bone resorbing margins and at the periphery of osteocyte lacunae adjacent to resorbing areas. Electron microscopic data suggests that collagenase is an extracellular enzyme foun at the periphery of osteocytes. In addition, abundant acid phosphatase activity was seen in the same cells that exhibited collagenase staining, lending credence to the destructive function of these cells. The chronic inflammatory reaction found in chronic otitis media appears to activate bone destruction through the dynamic activity of mononuclear inflammatory cells and stimulates bone cells to increase their destructive biochemical functions."}
{"id": "PMID:227319", "title": "gamma-Hydroxybutyric acid is not a GABA-mimetic agent in the spinal cord.", "content": "gamma-Hydroxybutyric acid (GHB), a pharmacologically active central nervous system constituent, has been postulated to function as a gamma-aminobutyric acid (GABA) agonist. This hypothesis was tested directly on GABAergic synapses in isolated, superfused frog spinal cord. Addition of GHB to the superfusate produced effects on primary afferent terminals that were distinctly different from the effects of GABA. Thus, although both compounds depressed dorsal root potentials, GHB hyperpolarized terminals while GABA depolarized the same structures. The GABA responses were antagonized by bicuculline and picrotoxin, but these alkaloids did not change GHB's actions. In addition, GHB altered neither high-affinity uptake by cord slices, nor potassium-evoked release of tritiated GABA from them. GHB did not directly release GABA from spinal slices preloaded with [3H]GABA. These observations suggest that the central nervous system actions of GHB are not dependent upon its ability to activate GABAergic synapses or to modify GABAergic mechanisms.", "contents": "gamma-Hydroxybutyric acid is not a GABA-mimetic agent in the spinal cord. gamma-Hydroxybutyric acid (GHB), a pharmacologically active central nervous system constituent, has been postulated to function as a gamma-aminobutyric acid (GABA) agonist. This hypothesis was tested directly on GABAergic synapses in isolated, superfused frog spinal cord. Addition of GHB to the superfusate produced effects on primary afferent terminals that were distinctly different from the effects of GABA. Thus, although both compounds depressed dorsal root potentials, GHB hyperpolarized terminals while GABA depolarized the same structures. The GABA responses were antagonized by bicuculline and picrotoxin, but these alkaloids did not change GHB's actions. In addition, GHB altered neither high-affinity uptake by cord slices, nor potassium-evoked release of tritiated GABA from them. GHB did not directly release GABA from spinal slices preloaded with [3H]GABA. These observations suggest that the central nervous system actions of GHB are not dependent upon its ability to activate GABAergic synapses or to modify GABAergic mechanisms."}
{"id": "PMID:227318", "title": "Genetic diversity of Athabaskan Indians.", "content": "If Athabaskan Indians are subdivided by linguistic group, a wide diversity in gene frequencies is disclosed. This diversity approximated that found when linguistically unrelated groups were compared. It was greater than that found for Eskimo-Aleus, even though the latter are more heterogeneous linguistically and subject to a wider variety of environmental conditions. Contiguity, geographic distance, and linguistic similarity were not reflected in similarity of gene frequencies. The gene found for Athabaskans appear to be the result of random process-survivor effects and genetic drift of small isolated groups. They appear to be of no value in detecting ethnic relationships.", "contents": "Genetic diversity of Athabaskan Indians. If Athabaskan Indians are subdivided by linguistic group, a wide diversity in gene frequencies is disclosed. This diversity approximated that found when linguistically unrelated groups were compared. It was greater than that found for Eskimo-Aleus, even though the latter are more heterogeneous linguistically and subject to a wider variety of environmental conditions. Contiguity, geographic distance, and linguistic similarity were not reflected in similarity of gene frequencies. The gene found for Athabaskans appear to be the result of random process-survivor effects and genetic drift of small isolated groups. They appear to be of no value in detecting ethnic relationships."}
{"id": "PMID:227324", "title": "[Effect of phosphorus on polymyxin B biosynthesis by B. polymyxa 1538 on media of varying makeup].", "content": "The effect of phosphorus on biosynthesis of polymyxin B by B. polymyxa 1538 was studied and its optimal concentration in the synthetic and two complex media was determined. Correlation between the culture growth and consumption of the main components, on the one hand, and concentration of phosphorus in the medium, on the other hand, was found. It was shown that the effect of phosphorus on biosynthesis of polymyxin B did not depend on the carbon source in the medium and aeration conditions.", "contents": "[Effect of phosphorus on polymyxin B biosynthesis by B. polymyxa 1538 on media of varying makeup]. The effect of phosphorus on biosynthesis of polymyxin B by B. polymyxa 1538 was studied and its optimal concentration in the synthetic and two complex media was determined. Correlation between the culture growth and consumption of the main components, on the one hand, and concentration of phosphorus in the medium, on the other hand, was found. It was shown that the effect of phosphorus on biosynthesis of polymyxin B did not depend on the carbon source in the medium and aeration conditions."}
{"id": "PMID:227327", "title": "Cytogenesis in the rat adrenal cortex: evidence for an ACTH-induced centripetal cell migration from the zona glomerulosa.", "content": "The mechanism underlying cytogenesis in the adrenal cortex of ACTH-treated rats was investigated. ACTH was found to increase the number of parenchymal cells in the zona fasciculata as well as that of \"S\" phase cells in the inner half of the zona glomerulosa and in the outer third of the zona fasciculata. The fate of 3H-thymidine labelled cells in ACTH-administered rats was also autoradiographically followed. The results are consistent with the hypothesis that the ACTH-provoked hyperplasia in the zona fasciculata involves the centripetal migration of newly-formed parenchymal cells from the zona glomerulosa.", "contents": "Cytogenesis in the rat adrenal cortex: evidence for an ACTH-induced centripetal cell migration from the zona glomerulosa. The mechanism underlying cytogenesis in the adrenal cortex of ACTH-treated rats was investigated. ACTH was found to increase the number of parenchymal cells in the zona fasciculata as well as that of \"S\" phase cells in the inner half of the zona glomerulosa and in the outer third of the zona fasciculata. The fate of 3H-thymidine labelled cells in ACTH-administered rats was also autoradiographically followed. The results are consistent with the hypothesis that the ACTH-provoked hyperplasia in the zona fasciculata involves the centripetal migration of newly-formed parenchymal cells from the zona glomerulosa."}
{"id": "PMID:227336", "title": "The serum protein pattern in primary hepatoma and amoebic liver abscess.", "content": "A study of the serum proteins pattern of 30 patients with primary liver cell carcinoma and 11 with amoebic liver abscess was carried out. When compared with controls significant differences were found for both conditions in the values of pre-albumin, transferrin, albumin, haptoglobin, alpha 2-macroglobulin, and alpha 2HS-glycoprotein. In the differential diagnosis of amoebic liver abscess and primary hepatic carcinoma, the estimation of albumin, alpha 1-acid glycoprotein, haptoglobin ceruloplasmin, alpha 2H2-glycoprotein and transferrin was found helpful.", "contents": "The serum protein pattern in primary hepatoma and amoebic liver abscess. A study of the serum proteins pattern of 30 patients with primary liver cell carcinoma and 11 with amoebic liver abscess was carried out. When compared with controls significant differences were found for both conditions in the values of pre-albumin, transferrin, albumin, haptoglobin, alpha 2-macroglobulin, and alpha 2HS-glycoprotein. In the differential diagnosis of amoebic liver abscess and primary hepatic carcinoma, the estimation of albumin, alpha 1-acid glycoprotein, haptoglobin ceruloplasmin, alpha 2H2-glycoprotein and transferrin was found helpful."}
{"id": "PMID:227337", "title": "[Coproantibodies in intestinal amebiasis].", "content": "E. histolytica tissue invasion induces IgG and IgM and probably IgA serum antibody formation of different types in the intestinal mucosa. 21 children with intestinal invasive amebiasis were studied. Samples were taken from peripheral blood and stools during diagnostic studies and three weeks later. Contraimmunoelectrophoretic antibody determinations and indirect hemagglutination tests IH were made in an attempt to demonstrate its true nature. During the acute phase (first sample), results showed antibodies against amoeba in stools by CIE in 57 per cent and by IH in 80 per cent; in serum, results were 38 and 76 per cent respectively. In the second sample and three weeks after diagnosis was established a decrease in the number of patients with coproantibodies against amoeba was observed and the number of patients with serum antibodies increased. We are also providing evidence that supports the IgG and IgA nature of coproantibodies against amoeba. These results suggest the presence of a local immunological reaction in invasive amebiasis.", "contents": "[Coproantibodies in intestinal amebiasis]. E. histolytica tissue invasion induces IgG and IgM and probably IgA serum antibody formation of different types in the intestinal mucosa. 21 children with intestinal invasive amebiasis were studied. Samples were taken from peripheral blood and stools during diagnostic studies and three weeks later. Contraimmunoelectrophoretic antibody determinations and indirect hemagglutination tests IH were made in an attempt to demonstrate its true nature. During the acute phase (first sample), results showed antibodies against amoeba in stools by CIE in 57 per cent and by IH in 80 per cent; in serum, results were 38 and 76 per cent respectively. In the second sample and three weeks after diagnosis was established a decrease in the number of patients with coproantibodies against amoeba was observed and the number of patients with serum antibodies increased. We are also providing evidence that supports the IgG and IgA nature of coproantibodies against amoeba. These results suggest the presence of a local immunological reaction in invasive amebiasis."}
{"id": "PMID:227338", "title": "[Acute infectious gastroenteritis. Etiology and its correlation with clinical manifestations and fecal mucus].", "content": "343 children with acute diarrhea were studied from january 1976 to september 1977. Rotavirus was the agent most frequently isolated (18 per cent) followed by Shigella (12 per cent) and Salmonella (10 per cent). Enterotoxigenic E. coli was identified in 8 per cent and invasive E. coli only in two cases. 80 per cent of isolated rotavirus fell in the neonate group and 25 per cent in the infant group. Diarrhea caused by rotavirus had a short duration, fever was negligible and abundant liquid stools were present without leukocytes in the fecal mucus and with a high percentage (48 per cent) of transient lactose intolerance. Polymorphonuclear leukocytes were found in fecal mucus in 75 per cent of cases caused by Shigella and only in 40 per cent of cases where the causal agent was Salmonella.", "contents": "[Acute infectious gastroenteritis. Etiology and its correlation with clinical manifestations and fecal mucus]. 343 children with acute diarrhea were studied from january 1976 to september 1977. Rotavirus was the agent most frequently isolated (18 per cent) followed by Shigella (12 per cent) and Salmonella (10 per cent). Enterotoxigenic E. coli was identified in 8 per cent and invasive E. coli only in two cases. 80 per cent of isolated rotavirus fell in the neonate group and 25 per cent in the infant group. Diarrhea caused by rotavirus had a short duration, fever was negligible and abundant liquid stools were present without leukocytes in the fecal mucus and with a high percentage (48 per cent) of transient lactose intolerance. Polymorphonuclear leukocytes were found in fecal mucus in 75 per cent of cases caused by Shigella and only in 40 per cent of cases where the causal agent was Salmonella."}
{"id": "PMID:227334", "title": "Lipids and lipoproteins in subjects at 1,000 and 3,500 meter altitudes.", "content": "To assess the relationship between altitude, atherogenic, and anti-atherogenic lipoprotein cholesterols (low- [C-LDL] and high [C-HDL] density lipoprotein cholesterols, respectively), 136 and 94 Venezuelan Mestizos living at 1,000 and 3,500 in elevation were studied. The two groups did not differ in regard to height, weight, ethnic origin, social or economic status, nutritional patterns, age, or occupation. Both groups had a high level of daily physical exertion, an imperative in their subsistence rural agricultural economy. Due to the mountainous terrain, high altitude residents were thought to have increased levels of physical activity. Males and females at high altitude had significantly lower plasma total cholesterol and C-LDL levels, and slightly lower C-HDL levels than those at low altitudes. It is speculated that reduced coronary heart disease event rates at high altitude might be related to lower levels of the atherogenic lipoprotein cholesterol, C-LDL.", "contents": "Lipids and lipoproteins in subjects at 1,000 and 3,500 meter altitudes. To assess the relationship between altitude, atherogenic, and anti-atherogenic lipoprotein cholesterols (low- [C-LDL] and high [C-HDL] density lipoprotein cholesterols, respectively), 136 and 94 Venezuelan Mestizos living at 1,000 and 3,500 in elevation were studied. The two groups did not differ in regard to height, weight, ethnic origin, social or economic status, nutritional patterns, age, or occupation. Both groups had a high level of daily physical exertion, an imperative in their subsistence rural agricultural economy. Due to the mountainous terrain, high altitude residents were thought to have increased levels of physical activity. Males and females at high altitude had significantly lower plasma total cholesterol and C-LDL levels, and slightly lower C-HDL levels than those at low altitudes. It is speculated that reduced coronary heart disease event rates at high altitude might be related to lower levels of the atherogenic lipoprotein cholesterol, C-LDL."}
{"id": "PMID:227335", "title": "Effects of silica dust inhalation on the susceptibility of mice to influenza infection.", "content": "Mice were exposed to silica dust for durations of up to 36 wk. At intervals of 15, 21, 27, 33, and 36 wk, the ability of the splenic lymphocytes to respond to T and B cell mitogens were determined, and their ability to resist influenza virus infections was determined after 3 and 20 wk of exposure. These exposures had a depressing effect on the response to T cell mitogens at 21 and 27 wk of silica exposure, but there was no effect on the T cell responses after 15, 33, and 36 wk or on B cell responses after all exposure times. No changes could be detected in the ability of the mice to resist pulmonary influenza virus infections or in the survivors ability to form HI antibodies against this virus.", "contents": "Effects of silica dust inhalation on the susceptibility of mice to influenza infection. Mice were exposed to silica dust for durations of up to 36 wk. At intervals of 15, 21, 27, 33, and 36 wk, the ability of the splenic lymphocytes to respond to T and B cell mitogens were determined, and their ability to resist influenza virus infections was determined after 3 and 20 wk of exposure. These exposures had a depressing effect on the response to T cell mitogens at 21 and 27 wk of silica exposure, but there was no effect on the T cell responses after 15, 33, and 36 wk or on B cell responses after all exposure times. No changes could be detected in the ability of the mice to resist pulmonary influenza virus infections or in the survivors ability to form HI antibodies against this virus."}
{"id": "PMID:227340", "title": "Fluphenazine and social therapy in the aftercare of schizophrenic patients. Relapse analyses of a two-year controlled study of fluphenazine decanoate and fluphenazine hydrochloride.", "content": "The ability of long-acting fluphenazine decanoate and oral fluphenazine hydrochloride to forestall relapse among newly discharge schizophrenic patients is examined in the context of high and low degrees of social therapy (ST). A total of 105 patients were randomly assigned to the various treatments and maintained under controlled conditions for two years or until relapse. Relapse rates for all treatments remained traditionally high. Relpase rates for long-acting fluphenazine decanoate and oral fluphenazine hydrochloride are nearly identical in the first year, indicating that drug noncompliance does not adequately explain early schizophrenic relapse. However, patients who received long-acting fluphenazine decanoate and ST have a reduced risk of relapse over time. Relapsers who received long-acting fluphenazine decanoate appeared more affectively disturbed than other relapsers, yet both groups were diagnostically and symptomatically equivalent prior to treatment. Personal discomfort and intrafamilial stress are important predictors.", "contents": "Fluphenazine and social therapy in the aftercare of schizophrenic patients. Relapse analyses of a two-year controlled study of fluphenazine decanoate and fluphenazine hydrochloride. The ability of long-acting fluphenazine decanoate and oral fluphenazine hydrochloride to forestall relapse among newly discharge schizophrenic patients is examined in the context of high and low degrees of social therapy (ST). A total of 105 patients were randomly assigned to the various treatments and maintained under controlled conditions for two years or until relapse. Relapse rates for all treatments remained traditionally high. Relpase rates for long-acting fluphenazine decanoate and oral fluphenazine hydrochloride are nearly identical in the first year, indicating that drug noncompliance does not adequately explain early schizophrenic relapse. However, patients who received long-acting fluphenazine decanoate and ST have a reduced risk of relapse over time. Relapsers who received long-acting fluphenazine decanoate appeared more affectively disturbed than other relapsers, yet both groups were diagnostically and symptomatically equivalent prior to treatment. Personal discomfort and intrafamilial stress are important predictors."}
{"id": "PMID:227341", "title": "[Testing of solid tumors in childhood for sensitivity against cytostatic agents using an autoradiographic in vitro method (short-term method) (author's transl)].", "content": "The sensitivity of 37 solid tumours of children was tested in vitro towards cytostatic agents by means of an autoradiographic short-term method. Sensitivity was measured as the magnitude of inhibition of 3 H-thymidine incorporation. The test was performed with the cytotoxic agents Cyclophosphamide, Trenimon, Bleomycin, Adriamycin, Daunomycin, Actinomycin D, and Cytosin-Arabinosid in 9 Wilms' tumours, 9 neuroblastomas, 7 non-Hodgkin-lymphomas, 5 osteogenic sarcomas, 3 soft tissue sarcomas, and 4 special tumours. None of the tumours is resistant to all cytotoxic substances. The tumours show a marked individual sensitivity pattern, and, with few exceptions, they are sensitive against 2 or more cytostatics. This behaviour is explained mainly by the usually high proliferative activity of dysontogenetic tumours, malignant lymphomas and various sarcomas. The possibilities and limits of the short-term methods for sensitivity-testing are discussed critically and in detail. For the evaluation of the results of in vitro testing and of in vivo effectiveness the close coreelations are not always taken into consideration between the type of cytostatic agent and effect on tumour metabolism, cytostatic agent and proliferation kinetics of the tumour as well as the effect of the cytostatics and the nucleic acid precursor used for the test. Despite the methodological limitations preclinical testing should be preferred in comparison with unselected chemotherapy.", "contents": "[Testing of solid tumors in childhood for sensitivity against cytostatic agents using an autoradiographic in vitro method (short-term method) (author's transl)]. The sensitivity of 37 solid tumours of children was tested in vitro towards cytostatic agents by means of an autoradiographic short-term method. Sensitivity was measured as the magnitude of inhibition of 3 H-thymidine incorporation. The test was performed with the cytotoxic agents Cyclophosphamide, Trenimon, Bleomycin, Adriamycin, Daunomycin, Actinomycin D, and Cytosin-Arabinosid in 9 Wilms' tumours, 9 neuroblastomas, 7 non-Hodgkin-lymphomas, 5 osteogenic sarcomas, 3 soft tissue sarcomas, and 4 special tumours. None of the tumours is resistant to all cytotoxic substances. The tumours show a marked individual sensitivity pattern, and, with few exceptions, they are sensitive against 2 or more cytostatics. This behaviour is explained mainly by the usually high proliferative activity of dysontogenetic tumours, malignant lymphomas and various sarcomas. The possibilities and limits of the short-term methods for sensitivity-testing are discussed critically and in detail. For the evaluation of the results of in vitro testing and of in vivo effectiveness the close coreelations are not always taken into consideration between the type of cytostatic agent and effect on tumour metabolism, cytostatic agent and proliferation kinetics of the tumour as well as the effect of the cytostatics and the nucleic acid precursor used for the test. Despite the methodological limitations preclinical testing should be preferred in comparison with unselected chemotherapy."}
{"id": "PMID:227342", "title": "Total \"internal\" hemipelvectomy.", "content": "Several authors have described resections of tumorbearing parts of the pelvis including reconstructive plastic surgery. With extensive tumor growth present mutilating hemipelvectomies often have been the last resort. Even the most sophisticated prostheses hardly ever enabled the patients to walk again. We have therefore performed total \"internal\" hemipelvectomies in three cases. The necessary substitute consisted of half a pelvis made of polyacetal resin produced from a given model. The model's measures and shape was established by computer tomograms thus resulting in an individually shaped pelvis half. The operative procedure aims at the maintenance of osseous muscular insertions and origins and their reconstruction. Utmost care has to be taken in avoiding damage to nerves and vessels. Fixation of the implant is performed by screws aiming through the sacroiliac joint into ala and corpus of the sacrum and corticocancellous grafts incorporated in the implant. The symphyses are united by means of plate fixation. The hip joint is substituted by a total prosthesis. With the procedure described we have managed three cases of extensive malignant tumors of the pelvis. One patient suffered a nerve lesion and skin necrosis with infection. The two remaining patients are capable of weight-bearing and standing on the inflicted leg alone.", "contents": "Total \"internal\" hemipelvectomy. Several authors have described resections of tumorbearing parts of the pelvis including reconstructive plastic surgery. With extensive tumor growth present mutilating hemipelvectomies often have been the last resort. Even the most sophisticated prostheses hardly ever enabled the patients to walk again. We have therefore performed total \"internal\" hemipelvectomies in three cases. The necessary substitute consisted of half a pelvis made of polyacetal resin produced from a given model. The model's measures and shape was established by computer tomograms thus resulting in an individually shaped pelvis half. The operative procedure aims at the maintenance of osseous muscular insertions and origins and their reconstruction. Utmost care has to be taken in avoiding damage to nerves and vessels. Fixation of the implant is performed by screws aiming through the sacroiliac joint into ala and corpus of the sacrum and corticocancellous grafts incorporated in the implant. The symphyses are united by means of plate fixation. The hip joint is substituted by a total prosthesis. With the procedure described we have managed three cases of extensive malignant tumors of the pelvis. One patient suffered a nerve lesion and skin necrosis with infection. The two remaining patients are capable of weight-bearing and standing on the inflicted leg alone."}
{"id": "PMID:227343", "title": "Studies on the attachment of herpes simplex virus. Effect of trypsin treatment.", "content": "The adsorption of herpes simplex virus (HSV) to monolayers of trypsinized and mock-treated GMK-AH1 cells was studied by means of a microplaque technique. Plaque formation was nearly abolished for c:a 20 minutes and full sensitivity regained at 6--8 hours post trypsinization. The return of sensitivity to HSV was inhibited by cycloheximide and incubation at 4 degrees C. The sum of PFU in the supernatant and PFU successe modifying agents were without effect on the adsorption of HSV.", "contents": "Studies on the attachment of herpes simplex virus. Effect of trypsin treatment. The adsorption of herpes simplex virus (HSV) to monolayers of trypsinized and mock-treated GMK-AH1 cells was studied by means of a microplaque technique. Plaque formation was nearly abolished for c:a 20 minutes and full sensitivity regained at 6--8 hours post trypsinization. The return of sensitivity to HSV was inhibited by cycloheximide and incubation at 4 degrees C. The sum of PFU in the supernatant and PFU successe modifying agents were without effect on the adsorption of HSV."}
{"id": "PMID:227339", "title": "[Etiology of combined inhalational hydrocyanic acid and carbon monoxide poisoning].", "content": "A young man was found dead in a kitchen, that was partly burnt. Autopsy revealed, as cause of death, a combined intoxication following inhalation of carbon monoxide and hydrocyanic acid. Own investigations on the pyrolysis of pieces of furniture found in the kitchen (plastic plates containing melamine and plates containing formaldehyde) showed, that hydrocyanic acid was liberated through combustion of such substances and inhaled by the victim. The poisoning picture is discussed, and discussion includes especially considerations on the peculiar sensitivity of the brain toward the action of hydrocyanic acid and the relative insensitivity of the heart muscle. It is thought that the cause of such sensitivity difference lies in the physiological differences of the intracellular energy production. Finally the dangers of combustion gases developing from burning plastic materials are reemphasized.", "contents": "[Etiology of combined inhalational hydrocyanic acid and carbon monoxide poisoning]. A young man was found dead in a kitchen, that was partly burnt. Autopsy revealed, as cause of death, a combined intoxication following inhalation of carbon monoxide and hydrocyanic acid. Own investigations on the pyrolysis of pieces of furniture found in the kitchen (plastic plates containing melamine and plates containing formaldehyde) showed, that hydrocyanic acid was liberated through combustion of such substances and inhaled by the victim. The poisoning picture is discussed, and discussion includes especially considerations on the peculiar sensitivity of the brain toward the action of hydrocyanic acid and the relative insensitivity of the heart muscle. It is thought that the cause of such sensitivity difference lies in the physiological differences of the intracellular energy production. Finally the dangers of combustion gases developing from burning plastic materials are reemphasized."}
{"id": "PMID:227344", "title": "Taxonomic studies on strains of avian infectious bronchitis virus using neutralisation tests in tracheal organ cultures.", "content": "The antigenic relationships of 24 strains of avian infectious bronchitis virus (IBV) were investigated by serum neutralisation tests performed in chick embryo tracheal organ cultures. The serum dilution that neutralised 100 median ciliostatic doses (CD50) of virus was estimated from the linear relationship between varying concentrations of each virus strain and the neutralisation titre of homologous antiserum; this dilution defined 1 antibody unit. Antisera diluted to contain 20 antibody units were then tested by neutralisation against 1.5--2.5 log10 CD50 of each strain. Clusters of both strains and antisera in turn were established by methods of numerical taxonomy using as measures of resemblance Euclidean distance and correlation coefficient, and by analysis by principal components. These analyses identified a group of 8 similar strains; neutralisation of the remaining 16 strains was slight. Similar results were obtained by classifying antisera, except that a further group of 3 antisera was demonstrated, each having a neutralising capacity for most strains. Implications for vaccine formulation are discussed.", "contents": "Taxonomic studies on strains of avian infectious bronchitis virus using neutralisation tests in tracheal organ cultures. The antigenic relationships of 24 strains of avian infectious bronchitis virus (IBV) were investigated by serum neutralisation tests performed in chick embryo tracheal organ cultures. The serum dilution that neutralised 100 median ciliostatic doses (CD50) of virus was estimated from the linear relationship between varying concentrations of each virus strain and the neutralisation titre of homologous antiserum; this dilution defined 1 antibody unit. Antisera diluted to contain 20 antibody units were then tested by neutralisation against 1.5--2.5 log10 CD50 of each strain. Clusters of both strains and antisera in turn were established by methods of numerical taxonomy using as measures of resemblance Euclidean distance and correlation coefficient, and by analysis by principal components. These analyses identified a group of 8 similar strains; neutralisation of the remaining 16 strains was slight. Similar results were obtained by classifying antisera, except that a further group of 3 antisera was demonstrated, each having a neutralising capacity for most strains. Implications for vaccine formulation are discussed."}
{"id": "PMID:227345", "title": "The effect of pyrophosphate analogues on influenza virus RNA polymerase and influenza virus multiplication.", "content": "Analogues of pyrophosphate have been tested as inhibitors of influenza virus-RNA polymerase activity in cell-free assays. The most active compound, phosphonoformic acid (PFA), reduced the polymerase activity to 50 per cent at a concentration of 20 muM. The inhibition was dependent on the type of divalent cation present in the assay. PFA at a concentration of 400 muM also inhibited the influenza virus plaque formation by 90 per cent.", "contents": "The effect of pyrophosphate analogues on influenza virus RNA polymerase and influenza virus multiplication. Analogues of pyrophosphate have been tested as inhibitors of influenza virus-RNA polymerase activity in cell-free assays. The most active compound, phosphonoformic acid (PFA), reduced the polymerase activity to 50 per cent at a concentration of 20 muM. The inhibition was dependent on the type of divalent cation present in the assay. PFA at a concentration of 400 muM also inhibited the influenza virus plaque formation by 90 per cent."}
{"id": "PMID:227346", "title": "A new calicivirus isolated from a marine mammal.", "content": "A new serotype of calicivirus, designated as San Miguel sea lion virus type 6 (SMSV-6), was isolated from vesicular lesions on the flipper of a California sea lion pup. Serologic studies show that SMSV-6 neutralizing antibodies (SN) occur frequently among California sea lions and occasionally among northern fur seals. Feral swine, 1- to 6-week elephant seal pups and grey whales tested negative for SMSV-6 antibody.", "contents": "A new calicivirus isolated from a marine mammal. A new serotype of calicivirus, designated as San Miguel sea lion virus type 6 (SMSV-6), was isolated from vesicular lesions on the flipper of a California sea lion pup. Serologic studies show that SMSV-6 neutralizing antibodies (SN) occur frequently among California sea lions and occasionally among northern fur seals. Feral swine, 1- to 6-week elephant seal pups and grey whales tested negative for SMSV-6 antibody."}
{"id": "PMID:227347", "title": "[Radioautographic study of the localization of 3H-estradiol, 3H-histamine, and 3H-cyclic adenosine monophosphate in rat uterus].", "content": "The method of radioautography has demonstrated that 3H-estradiol adheres to the nuclei of some myometrium cells, 3H-histamine is accepted by the cytoplasm of the majority of the myometrium cells, 3H-cyclic-AMP is selectively bound by the endothelial cells of capillaries and small vessels in all layers of the uterus. From the data obtained it is possible to conclude that estradiol and its mediators, histamine and cyclic-AMP, specifically interact with different cells and with different cell structures.", "contents": "[Radioautographic study of the localization of 3H-estradiol, 3H-histamine, and 3H-cyclic adenosine monophosphate in rat uterus]. The method of radioautography has demonstrated that 3H-estradiol adheres to the nuclei of some myometrium cells, 3H-histamine is accepted by the cytoplasm of the majority of the myometrium cells, 3H-cyclic-AMP is selectively bound by the endothelial cells of capillaries and small vessels in all layers of the uterus. From the data obtained it is possible to conclude that estradiol and its mediators, histamine and cyclic-AMP, specifically interact with different cells and with different cell structures."}
{"id": "PMID:227348", "title": "[Intrauterine infections in the perinatal period].", "content": "The results of examinations of autopsy materials in Leningrad and the data from the literature indicate that infectious diseases occupy a significant place in perinatal mortality. It is emphasized that if the autopsy materials are not sufficiently examined using not only light but also immunofluorescent microscopy, a considerable portion of these infections is not diagnosed and the pathological proprocess in such cases in considered to be aspiration pneumonia, hyaline membrane disease, etc. The paper briefly characterizes intrauterine bacterial infections (listeriasis, syphilis, staphylococcal infections, etc.) with special reference to virus diseases (cytomegaly, herpes infection, lesions caused by respiratory viruses, etc) and mycoplasmosis. It is shown that a relatively high incidence of lesions is caused by respiratory viruses and particularly mycoplasma. The possibility of protozoan and mycotic lesions is also indicated. The frequent occurrence of combined intrauterine infections is emphasized.", "contents": "[Intrauterine infections in the perinatal period]. The results of examinations of autopsy materials in Leningrad and the data from the literature indicate that infectious diseases occupy a significant place in perinatal mortality. It is emphasized that if the autopsy materials are not sufficiently examined using not only light but also immunofluorescent microscopy, a considerable portion of these infections is not diagnosed and the pathological proprocess in such cases in considered to be aspiration pneumonia, hyaline membrane disease, etc. The paper briefly characterizes intrauterine bacterial infections (listeriasis, syphilis, staphylococcal infections, etc.) with special reference to virus diseases (cytomegaly, herpes infection, lesions caused by respiratory viruses, etc) and mycoplasmosis. It is shown that a relatively high incidence of lesions is caused by respiratory viruses and particularly mycoplasma. The possibility of protozoan and mycotic lesions is also indicated. The frequent occurrence of combined intrauterine infections is emphasized."}
{"id": "PMID:227349", "title": "Prevalence of antibody to hepatitis A virus in Sri Lanka.", "content": "Antibody to hepatitis A virus was studied by immune adherence hemagglutination using 287 serum specimens collected in 1975 by random sampling from healthy individuals living in Colomobo, Sri Lanka. The overall prevalence of antibody to the virus was 76.9% and the prevalence between males and females was approximately the same. The age-specific prevalence of the antibody indicated that hepatitis A in the area is mainly an infection during the early childhood.", "contents": "Prevalence of antibody to hepatitis A virus in Sri Lanka. Antibody to hepatitis A virus was studied by immune adherence hemagglutination using 287 serum specimens collected in 1975 by random sampling from healthy individuals living in Colomobo, Sri Lanka. The overall prevalence of antibody to the virus was 76.9% and the prevalence between males and females was approximately the same. The age-specific prevalence of the antibody indicated that hepatitis A in the area is mainly an infection during the early childhood."}
{"id": "PMID:227350", "title": "Immediate postembolization excision of glomus jugulare tumors: advantages of new combined techniques.", "content": "Preoperative percutaneous transfemoral catheter embolization of feeding vessels in glomus jugulare tumors, followed by immediate application of standard surgical techniques, presents the treatment of choice, allowing meticulous microsurgery with virtually complete hemostasis. Therefore, the surgeon can operate in a bloodless environment throughout the compressed and intricate anatomic field, amidst such important yet vulnerable structures as cranial nerves, inner ear, carotid artery, jugular bulb, venous sinuses, and dura, while reducing surgical error and functional deficit for the patient. Review of the last 11 cases of glomus jugulare tumors at UCLA shows that even extensive Alford grade 2 tumors of the middle ear, jugular bulb, and mastoid had only minor blood losses with this combined technique of embolization-immediate surgery, as compared with earlier surgical methods. Pertinent literature on glomus jugulare and its treatment is reviewed. Combined embolization and immediate surgery offer the best approach for treatment of resectable glomus jugulare tumors.", "contents": "Immediate postembolization excision of glomus jugulare tumors: advantages of new combined techniques. Preoperative percutaneous transfemoral catheter embolization of feeding vessels in glomus jugulare tumors, followed by immediate application of standard surgical techniques, presents the treatment of choice, allowing meticulous microsurgery with virtually complete hemostasis. Therefore, the surgeon can operate in a bloodless environment throughout the compressed and intricate anatomic field, amidst such important yet vulnerable structures as cranial nerves, inner ear, carotid artery, jugular bulb, venous sinuses, and dura, while reducing surgical error and functional deficit for the patient. Review of the last 11 cases of glomus jugulare tumors at UCLA shows that even extensive Alford grade 2 tumors of the middle ear, jugular bulb, and mastoid had only minor blood losses with this combined technique of embolization-immediate surgery, as compared with earlier surgical methods. Pertinent literature on glomus jugulare and its treatment is reviewed. Combined embolization and immediate surgery offer the best approach for treatment of resectable glomus jugulare tumors."}
{"id": "PMID:227355", "title": "Arteriolar rarefaction in hypertension.", "content": "The functional rarefaction of small arterioles previously reported at 6 weeks of age in the SHR has been shown to be a structural decrease in arteriolar density as well. In addition, the high \"occlusive tone\" normally found in young normotensive rats is observed in the older SHR. This elevated tone contributes to a functional rarefaction in the older SHR arterioles. The mechanism for the rarefaction appears to be related to the cAMP/cGMP second messenger system.", "contents": "Arteriolar rarefaction in hypertension. The functional rarefaction of small arterioles previously reported at 6 weeks of age in the SHR has been shown to be a structural decrease in arteriolar density as well. In addition, the high \"occlusive tone\" normally found in young normotensive rats is observed in the older SHR. This elevated tone contributes to a functional rarefaction in the older SHR arterioles. The mechanism for the rarefaction appears to be related to the cAMP/cGMP second messenger system."}
{"id": "PMID:227358", "title": "Transfer of carbohydrates on to nascent glycoprotein of vesicular stomatitis virus.", "content": "I studied the glycosylation in vivo of a viral envelope protein, the glycoprotein of vesicular stomatitis virus (VSV), by pulse labelling of virus-infected HeLa cells with 3H-labelled monosaccharides (mannose, glucosamine). Radioactivity was incorporated into the fraction of membrane-bound polyribosomes, although metabolic conversion of [3H]-mannose into amino acids was negligible. Dissociation of bound polyribosomes revealed that the radioactively co-purified with the peptidyl-tRNA. The nascent peptides were released by alkaline hydrolysis, immunoprecipitated and analysed by polyacrylamide-gel electrophoresis. It is apparent from the size distribution of the [3H]mannose-labelled nascent chains that attachment of carbohydrate starts when approximately half of the amino acid sequence of the viral glycoprotein has been synthesized.", "contents": "Transfer of carbohydrates on to nascent glycoprotein of vesicular stomatitis virus. I studied the glycosylation in vivo of a viral envelope protein, the glycoprotein of vesicular stomatitis virus (VSV), by pulse labelling of virus-infected HeLa cells with 3H-labelled monosaccharides (mannose, glucosamine). Radioactivity was incorporated into the fraction of membrane-bound polyribosomes, although metabolic conversion of [3H]-mannose into amino acids was negligible. Dissociation of bound polyribosomes revealed that the radioactively co-purified with the peptidyl-tRNA. The nascent peptides were released by alkaline hydrolysis, immunoprecipitated and analysed by polyacrylamide-gel electrophoresis. It is apparent from the size distribution of the [3H]mannose-labelled nascent chains that attachment of carbohydrate starts when approximately half of the amino acid sequence of the viral glycoprotein has been synthesized."}
{"id": "PMID:227359", "title": "Interaction of phosphorylase b with eosin. Influence of substrate and effectors on eosin-enzyme complexes.", "content": "The interactions of rabbit muscle glycogen phosphorylase b with Eosin (2',4',5',7'-tetrabromofluorescein) was studied. Eosin was found to be an effective inhibitor of the enzyme. The inhibition constants for the dye were estimated to be approx. 36 and 60 microM with respect to AMP and glucose 1-phosphate respectively. The binding of Eosin to phosphorylase b is accompanied by a red-shift of about 12 nm in the dye absorption-spectrum maximum, indicating low-polarity binding sites on the enzyme molecule for the dye. The absorbance in the difference absorption maximum at 537 nm was utilized to follow the conjugation of phosphorylase b with Eosin. Scatchard plots of the titration data revealed the existence of at least two classes of binding sites on the protein molecule for Eosin, and the dissociation constants measured in Tris/HCl buffer, pH 7.0 (IO.091), were 7.7 and 41.7 microM respectively. The influence of the substrates and effectors on Eosin-enzymes complexes was used to study the ligand-phosphorylase b interactions. IMP displaced the dye completely from the enzyme, indicating that there are two IMP-binding sites per phosphorylase b monomer. AMP binding to the enzyme with respect to Eosin concentration is of two types: a non-competitive one for the high-affinity site for AMP and a competitive one for the low-affinity site for the activator. The effects of glucose 6-phosphate, ATP, Pi and glycerol 2-phosphate in the system are in according dance with a partially competitive model. Glucoes 1-phosphate and UDP-glucose appear to affect only the high-affinity site for Eosin, whereas glucose and glycogen have no effect on Eosin-phosphorylase b complexes. Our results suggest that Eosin can be used as an efficient optical probe for studying the phosphorylase b system.", "contents": "Interaction of phosphorylase b with eosin. Influence of substrate and effectors on eosin-enzyme complexes. The interactions of rabbit muscle glycogen phosphorylase b with Eosin (2',4',5',7'-tetrabromofluorescein) was studied. Eosin was found to be an effective inhibitor of the enzyme. The inhibition constants for the dye were estimated to be approx. 36 and 60 microM with respect to AMP and glucose 1-phosphate respectively. The binding of Eosin to phosphorylase b is accompanied by a red-shift of about 12 nm in the dye absorption-spectrum maximum, indicating low-polarity binding sites on the enzyme molecule for the dye. The absorbance in the difference absorption maximum at 537 nm was utilized to follow the conjugation of phosphorylase b with Eosin. Scatchard plots of the titration data revealed the existence of at least two classes of binding sites on the protein molecule for Eosin, and the dissociation constants measured in Tris/HCl buffer, pH 7.0 (IO.091), were 7.7 and 41.7 microM respectively. The influence of the substrates and effectors on Eosin-enzymes complexes was used to study the ligand-phosphorylase b interactions. IMP displaced the dye completely from the enzyme, indicating that there are two IMP-binding sites per phosphorylase b monomer. AMP binding to the enzyme with respect to Eosin concentration is of two types: a non-competitive one for the high-affinity site for AMP and a competitive one for the low-affinity site for the activator. The effects of glucose 6-phosphate, ATP, Pi and glycerol 2-phosphate in the system are in according dance with a partially competitive model. Glucoes 1-phosphate and UDP-glucose appear to affect only the high-affinity site for Eosin, whereas glucose and glycogen have no effect on Eosin-phosphorylase b complexes. Our results suggest that Eosin can be used as an efficient optical probe for studying the phosphorylase b system."}
{"id": "PMID:227360", "title": "Separation and purification of the alkaline phosphatase and a phosphodiesterase from Halobacterium cutirubrum.", "content": "1. Halobacterium cutirubrum alkaline phosphatase is associated in crude extracts with a phosphodiesterase. 2. The enzymes were stabilized in buffers containing both (NH4)2SO4 and 10 mM-Mn2+. 3. Adsorption chromatography on Sepharose 6B/agarose-gel columns in the presence of 1.4M-(NH4)2SO4 gave a phosphatase-free phosphodiesterase and the alkaline phosphatase associated with some phosphodiesterase activity. 4. Further chromatography of the separated enzymes gave a good recovery of greater than 600-fold purified phosphodiesterase and greater than 3000-fold purified alkaline phosphatase. 5. The requirements of these enzymes and their relationship to each other was examined. 6. A detailed study showed that the alkaline phosphatase was adsorbed at least partially to agarose and dextran columns at all (NH4)2SO4 concentrations from 0.25 to 2M. 7. In contrast, no adsorption of the enzyme or protein standards was evident in 2.5M-KCl/l M-NaCl or 0.25 M-KCl/0.1 M-NaCl, in agreement with previous studies by Louis, Peterkin & Fitt [(1971) Biochem. J. 121, 635-641], thus confirming the validity of gel filtration in 2.5 M-KCl/1 M-NaCl as a method for determining the approximate molecular weights of extremehalophile proteins.", "contents": "Separation and purification of the alkaline phosphatase and a phosphodiesterase from Halobacterium cutirubrum. 1. Halobacterium cutirubrum alkaline phosphatase is associated in crude extracts with a phosphodiesterase. 2. The enzymes were stabilized in buffers containing both (NH4)2SO4 and 10 mM-Mn2+. 3. Adsorption chromatography on Sepharose 6B/agarose-gel columns in the presence of 1.4M-(NH4)2SO4 gave a phosphatase-free phosphodiesterase and the alkaline phosphatase associated with some phosphodiesterase activity. 4. Further chromatography of the separated enzymes gave a good recovery of greater than 600-fold purified phosphodiesterase and greater than 3000-fold purified alkaline phosphatase. 5. The requirements of these enzymes and their relationship to each other was examined. 6. A detailed study showed that the alkaline phosphatase was adsorbed at least partially to agarose and dextran columns at all (NH4)2SO4 concentrations from 0.25 to 2M. 7. In contrast, no adsorption of the enzyme or protein standards was evident in 2.5M-KCl/l M-NaCl or 0.25 M-KCl/0.1 M-NaCl, in agreement with previous studies by Louis, Peterkin & Fitt [(1971) Biochem. J. 121, 635-641], thus confirming the validity of gel filtration in 2.5 M-KCl/1 M-NaCl as a method for determining the approximate molecular weights of extremehalophile proteins."}
{"id": "PMID:227361", "title": "The development of SS'-polymethylenebis(methanethiosulphonates) as reversible cross-linking reagents for thiol groups and their use to form stable catalytically active cross-linked dimers within glyceraldehyde 3-phosphate dehydrogenase.", "content": "The synthesis of a series of SS'-polymethylenebis(methanethiosulphonates) including the pentane, hexane, octane, decane and dodecane derivatives is described. These derivatives were synthesized by condensation between dibromoalkanes and potassium methanethiosulphonate in refluxing methanol and this seems an especially versatile reaction for the synthesis of asymmetric thiosulphonate derivatives. The synthesis of SS'-[1,8-3H4]-octamethylenebis(methanethiosulphonate) was also perfomed. Cross-linking was demonstrated in the four enzymes lactate dehydrogenase, phosphofructokinase, pyruvate kinase and glyceraldehyde 3-phosphate dehydrogenase. For all four enzymes cross-linking was efficiently reversed by reducing conditions in denaturing solvents. The reaction with glyceraldehyde 3-phosphate dehydrogenase was unique in that only the cross-linked dimer was produced in significant amounts (greater than 90% of total products as dimer). This reaction was followed in detail with radioactive cross-linking reagent. Inhibition of enzyme activity was extremely fast and showed an asymmetric distribution of enzyme activity on subunits. Thus complete modification of only one subunit resulted in up to 75% inhibition of enzyme activity. Reaction of glyceraldehyde 3-phosphate dehydrogenase with 1.25 mol of SS'-octamethylenebis(methanethiosulphonate) per mol of enzyme subunit produced two species of protein. The first species was obtained in 20% yield and was only partially re-activated on mild reduction with 2-mercaptoethanol. The second species was isolated in 66% yield and was completely re-activated on mild reduction. Before reduction there was 4 mol of inhibitor per tetramer for the latter species, and more than 95% of the enzyme was present as a dimer on non-reducing electrophoresis. After mild reduction 2 mol of inhibitor was still bound per tetramer, the enzyme was now catalytically active and the dimer was still the major structure on non-reducing electrophoresis. Thus mild reduction of SS'-octamethylenebis(methanethiosulphonate-treated glyceraldehyde 3-phosphate dehydrogenase enabled the production of active enzyme in which there is a stable cross-link across one of the molecular axes of the tetrameric enzyme. This cross-link was only reversed if reduction was performed when the enzyme was denatured. The molecular weight of cross-linked and re-activated cross-linked glyceraldehyde 3-phosphate dehydrogenase was established as 144000 (tetramer) by sucrose-density-gradient centrifugation. These observations are interpreted in terms of the molecular structure of glyceraldehyde 3-phosphate dehydrogenase.", "contents": "The development of SS'-polymethylenebis(methanethiosulphonates) as reversible cross-linking reagents for thiol groups and their use to form stable catalytically active cross-linked dimers within glyceraldehyde 3-phosphate dehydrogenase. The synthesis of a series of SS'-polymethylenebis(methanethiosulphonates) including the pentane, hexane, octane, decane and dodecane derivatives is described. These derivatives were synthesized by condensation between dibromoalkanes and potassium methanethiosulphonate in refluxing methanol and this seems an especially versatile reaction for the synthesis of asymmetric thiosulphonate derivatives. The synthesis of SS'-[1,8-3H4]-octamethylenebis(methanethiosulphonate) was also perfomed. Cross-linking was demonstrated in the four enzymes lactate dehydrogenase, phosphofructokinase, pyruvate kinase and glyceraldehyde 3-phosphate dehydrogenase. For all four enzymes cross-linking was efficiently reversed by reducing conditions in denaturing solvents. The reaction with glyceraldehyde 3-phosphate dehydrogenase was unique in that only the cross-linked dimer was produced in significant amounts (greater than 90% of total products as dimer). This reaction was followed in detail with radioactive cross-linking reagent. Inhibition of enzyme activity was extremely fast and showed an asymmetric distribution of enzyme activity on subunits. Thus complete modification of only one subunit resulted in up to 75% inhibition of enzyme activity. Reaction of glyceraldehyde 3-phosphate dehydrogenase with 1.25 mol of SS'-octamethylenebis(methanethiosulphonate) per mol of enzyme subunit produced two species of protein. The first species was obtained in 20% yield and was only partially re-activated on mild reduction with 2-mercaptoethanol. The second species was isolated in 66% yield and was completely re-activated on mild reduction. Before reduction there was 4 mol of inhibitor per tetramer for the latter species, and more than 95% of the enzyme was present as a dimer on non-reducing electrophoresis. After mild reduction 2 mol of inhibitor was still bound per tetramer, the enzyme was now catalytically active and the dimer was still the major structure on non-reducing electrophoresis. Thus mild reduction of SS'-octamethylenebis(methanethiosulphonate-treated glyceraldehyde 3-phosphate dehydrogenase enabled the production of active enzyme in which there is a stable cross-link across one of the molecular axes of the tetrameric enzyme. This cross-link was only reversed if reduction was performed when the enzyme was denatured. The molecular weight of cross-linked and re-activated cross-linked glyceraldehyde 3-phosphate dehydrogenase was established as 144000 (tetramer) by sucrose-density-gradient centrifugation. These observations are interpreted in terms of the molecular structure of glyceraldehyde 3-phosphate dehydrogenase."}
{"id": "PMID:227362", "title": "Detergent activation and solubilization of 2':3'-cyclic nucleotide 3'-phosphodiesterase from isolated myelin and c6 cells.", "content": "Several detergents were investigated for their ability to increase activity of 2':3'-cyclic nucleotide 3'-phosphodiesterase in isolated myelin. The ability of Triton X-100 and Sulfobetaine DLH to solubilize the enzyme was also examined. Solubilization with Triton X-100 was only effective in the presence of salt, for example with NaCl 51% of the activity was solubilized. A single extraction with Sulfobetaine DLH yielded slightly more solubilized enzyme and did not require added salt. Both activation and solubilization of 2':3'-cyclic nucleotide 3'-phosphodiesterase appeared to be similarly dependent on detergent concentration, suggesting a common action of the detergent in the two processes. Myelin basic protein was solubilized more readily than the enzyme. In contrast with the enzyme in myelin, 2':3'-cyclic nucleotide 3'-phosphodiesterase activity in C6 cells was not increased in the presence of Triton X-100, and was partially solubilized by either Triton X-100 or NaCl alone. No myelin basic protein could be detected in C6 cells by radioimmunoassay.", "contents": "Detergent activation and solubilization of 2':3'-cyclic nucleotide 3'-phosphodiesterase from isolated myelin and c6 cells. Several detergents were investigated for their ability to increase activity of 2':3'-cyclic nucleotide 3'-phosphodiesterase in isolated myelin. The ability of Triton X-100 and Sulfobetaine DLH to solubilize the enzyme was also examined. Solubilization with Triton X-100 was only effective in the presence of salt, for example with NaCl 51% of the activity was solubilized. A single extraction with Sulfobetaine DLH yielded slightly more solubilized enzyme and did not require added salt. Both activation and solubilization of 2':3'-cyclic nucleotide 3'-phosphodiesterase appeared to be similarly dependent on detergent concentration, suggesting a common action of the detergent in the two processes. Myelin basic protein was solubilized more readily than the enzyme. In contrast with the enzyme in myelin, 2':3'-cyclic nucleotide 3'-phosphodiesterase activity in C6 cells was not increased in the presence of Triton X-100, and was partially solubilized by either Triton X-100 or NaCl alone. No myelin basic protein could be detected in C6 cells by radioimmunoassay."}
{"id": "PMID:227363", "title": "Neuraminidase inhibition by chemically sulphated glycopeptides.", "content": "Chemically sulphated glycopeptides (derived from pig duodenal mucosa) inhibited Clostridium perfringens neuraminidase (EC 3.2.1.18) activity in a pH-dependent manner. Analysis of inhibition kinetics data indicated that, although the enzyme inhibition could not be categorized into any of the classical types of inhibition, it could be interpreted as a function of the size and shape of the substrates used. The enzyme activity was inhibited by 86% and 40% when tested with bovine submaxillary-gland mucin (mol. wt. 4 x 10(5)-40 x 10(5) and N-acetylneuraminyl-lactose (mol. wt. 633) as substrates respectively. Presence of sulphated glycopeptide did not affect the binding of N-acetylneuraminic acid (mol. wt. 309), a competitive inhibitor of Vibrio cholerae neuraminidase, to the enzyme active site. The enzyme inhibition was thus considered to be due to steric hindrance as a consequence of the non-specific interactions between the enzyme molecule and polyanionic sulphated glycopeptide affecting the differential accessibility of the substrate molecules to the enzyme active site. The enzyme-inhibitor interaction could be suppressed by rapid and many-fold dilution of the reaction mixture, by concurrent addition of the inactive enzyme or by partial removal of the sulphate esters from the sulphated glycopeptide molecule by the action of Helix pomatia arylsulphatase (EC 3.1.6.1).", "contents": "Neuraminidase inhibition by chemically sulphated glycopeptides. Chemically sulphated glycopeptides (derived from pig duodenal mucosa) inhibited Clostridium perfringens neuraminidase (EC 3.2.1.18) activity in a pH-dependent manner. Analysis of inhibition kinetics data indicated that, although the enzyme inhibition could not be categorized into any of the classical types of inhibition, it could be interpreted as a function of the size and shape of the substrates used. The enzyme activity was inhibited by 86% and 40% when tested with bovine submaxillary-gland mucin (mol. wt. 4 x 10(5)-40 x 10(5) and N-acetylneuraminyl-lactose (mol. wt. 633) as substrates respectively. Presence of sulphated glycopeptide did not affect the binding of N-acetylneuraminic acid (mol. wt. 309), a competitive inhibitor of Vibrio cholerae neuraminidase, to the enzyme active site. The enzyme inhibition was thus considered to be due to steric hindrance as a consequence of the non-specific interactions between the enzyme molecule and polyanionic sulphated glycopeptide affecting the differential accessibility of the substrate molecules to the enzyme active site. The enzyme-inhibitor interaction could be suppressed by rapid and many-fold dilution of the reaction mixture, by concurrent addition of the inactive enzyme or by partial removal of the sulphate esters from the sulphated glycopeptide molecule by the action of Helix pomatia arylsulphatase (EC 3.1.6.1)."}
{"id": "PMID:227364", "title": "Effect of O-sulphate groups in lactose and N-acetylneuraminyl-lactose on their enzymic hydrolysis.", "content": "1. Lactose 6'-O-sulphate, N-acetylneuraminyl-(alpha 2 leads to 3)-D-lactose 6'-O-sulphate, N-acetylneuraminyl ?-O-sulphate-(alpha 2 leads to 3)-D-lactose 6'0-O-sulphate, N-acetylneuraminyl ?-O-sulphate-(alpha 2 leads to 6)-D-lactose and N-acetylneuraminyl-(alpha 2 leads to 3)- and -(alpha 2 leads to 6))-lactose 6'-O-sulphate were prepared by chemical sulphation of lactose, N-acetylneuraminyl-lactose and tis isomers by using pyridine-SO3 reagent. 2. Significant kinetic differences were observed in the enzymic hydrolysis of the sulphated derivatives compared with unsubstituted substrates. 3. In the case of reactions catalysed by rat liver lysosomal and Clostridium perfringens neuraminidases (EC 3.2.1.18), the presence of an O-sulphate group in the N-acetylneuraminyl moiety affected the reaction by decreasing the Km and the Vmax, its presence in the galactosyl moiety affected the reaction by decreasing the Km and increasing the Vmax. and its presence in both N-acetylneuraminyl and galactosyl moieties decreased the Km and the Vmax. of the reaction. 4. Mixed-substrate reaction kinetic data indicated competition between the sulphated and unsubstituted substrates for the same active sites on the neuraminidase molecule. 5. Lactose 6'-O-sulphate neither behaved as a substrate nor acted as an inhibitor with respect to unsubstituted lactose and p-nitrophenyl beta-D-galactopyranoside when tested with lactase of suckling rat intestine and Escherichia coli beta-D-galactosidase (EC 3.2.1.23). 6. Preliminary investigation also indicated that, whereas glucose 6-O-sulphate and glucose 3-O-sulphate were were neither substrate nor inhibitor of glucose oxidase (EC 1.1.3.4), galactose 6-O-sulphate was oxidized half as fast as unsubstituted galactose by galactose dehydrogenase (EC 1.1.1.48).", "contents": "Effect of O-sulphate groups in lactose and N-acetylneuraminyl-lactose on their enzymic hydrolysis. 1. Lactose 6'-O-sulphate, N-acetylneuraminyl-(alpha 2 leads to 3)-D-lactose 6'-O-sulphate, N-acetylneuraminyl ?-O-sulphate-(alpha 2 leads to 3)-D-lactose 6'0-O-sulphate, N-acetylneuraminyl ?-O-sulphate-(alpha 2 leads to 6)-D-lactose and N-acetylneuraminyl-(alpha 2 leads to 3)- and -(alpha 2 leads to 6))-lactose 6'-O-sulphate were prepared by chemical sulphation of lactose, N-acetylneuraminyl-lactose and tis isomers by using pyridine-SO3 reagent. 2. Significant kinetic differences were observed in the enzymic hydrolysis of the sulphated derivatives compared with unsubstituted substrates. 3. In the case of reactions catalysed by rat liver lysosomal and Clostridium perfringens neuraminidases (EC 3.2.1.18), the presence of an O-sulphate group in the N-acetylneuraminyl moiety affected the reaction by decreasing the Km and the Vmax, its presence in the galactosyl moiety affected the reaction by decreasing the Km and increasing the Vmax. and its presence in both N-acetylneuraminyl and galactosyl moieties decreased the Km and the Vmax. of the reaction. 4. Mixed-substrate reaction kinetic data indicated competition between the sulphated and unsubstituted substrates for the same active sites on the neuraminidase molecule. 5. Lactose 6'-O-sulphate neither behaved as a substrate nor acted as an inhibitor with respect to unsubstituted lactose and p-nitrophenyl beta-D-galactopyranoside when tested with lactase of suckling rat intestine and Escherichia coli beta-D-galactosidase (EC 3.2.1.23). 6. Preliminary investigation also indicated that, whereas glucose 6-O-sulphate and glucose 3-O-sulphate were were neither substrate nor inhibitor of glucose oxidase (EC 1.1.3.4), galactose 6-O-sulphate was oxidized half as fast as unsubstituted galactose by galactose dehydrogenase (EC 1.1.1.48)."}
{"id": "PMID:227365", "title": "Regulation of kinase reactions in pig heart pyruvate dehydrogenase complex.", "content": "1. Pig heart pyruvate dehydrogenase complex is inactivated by phosphorylation (MgATP2-) of an alpha-chain of the decarboxylase component. Three serine residues may be phosphorylated, one of which (site 1) is the major inactivating site. 2. The relative rates of phosphorylation are site 1 greater than 2 greater than site 3. 3. The kinetics of the inactivating phosphorylation were investigated by measuring inactivation of the complex with MgATP2-. The apparent Km for the Mg complex of ATP was 25.5 microM; ADP was a competitive inhibitor (Ki 69.8 microM) and sodium pyruvate an uncompetitive inhibitor (Ki 2.8 microM). Inactivation was accelerated by increasing concentration ratios of NADH/NAD+ and of acetyl-CoA/CoA. 4. The kinetics of additional phosphorylations (predominantly site 2 under these conditions) were investigated by measurement of 32P incorporation into non-radioactive pyruvate dehydrogenase phosphate containing 3-6% of active complex, and assumed from parrallel experiments with 32P labelling to contain 91% of protein-bound phosphate in site 1 and 9% in site 2. 5. The apparent Km for the Mg complex of ATP was 10.1 microM; ADP was a competitive inhibitor (Ki 31.5 microM) and sodium pyruvate an uncompetitive inhibitor (Ki 1.1 mM). 6. Incorporation was accelerated by increasing concentration ratios of NADH/NAD+ and of acetyl-CoA/CoA, although it was less marked at the highest ratios.", "contents": "Regulation of kinase reactions in pig heart pyruvate dehydrogenase complex. 1. Pig heart pyruvate dehydrogenase complex is inactivated by phosphorylation (MgATP2-) of an alpha-chain of the decarboxylase component. Three serine residues may be phosphorylated, one of which (site 1) is the major inactivating site. 2. The relative rates of phosphorylation are site 1 greater than 2 greater than site 3. 3. The kinetics of the inactivating phosphorylation were investigated by measuring inactivation of the complex with MgATP2-. The apparent Km for the Mg complex of ATP was 25.5 microM; ADP was a competitive inhibitor (Ki 69.8 microM) and sodium pyruvate an uncompetitive inhibitor (Ki 2.8 microM). Inactivation was accelerated by increasing concentration ratios of NADH/NAD+ and of acetyl-CoA/CoA. 4. The kinetics of additional phosphorylations (predominantly site 2 under these conditions) were investigated by measurement of 32P incorporation into non-radioactive pyruvate dehydrogenase phosphate containing 3-6% of active complex, and assumed from parrallel experiments with 32P labelling to contain 91% of protein-bound phosphate in site 1 and 9% in site 2. 5. The apparent Km for the Mg complex of ATP was 10.1 microM; ADP was a competitive inhibitor (Ki 31.5 microM) and sodium pyruvate an uncompetitive inhibitor (Ki 1.1 mM). 6. Incorporation was accelerated by increasing concentration ratios of NADH/NAD+ and of acetyl-CoA/CoA, although it was less marked at the highest ratios."}
{"id": "PMID:227366", "title": "1H nuclear-magnetic-resonance spectra of the methyl group of the acetamido moiety and the structure of acid glycosaminoglycans in solution.", "content": "The 1H resonances of the methyl group in the acetamido moiety of several types of glycosaminoglycans are reported at 300 MHz in 2H2O. Dermatan sulphates with various L-iduronate/D-glucuronate ratios are compared with chrondroitin sulphates with various contents and positions of substitution of sulphate esters. Hyaluronate oligomers are compared with 2-acetamido-2-deoxy-D-glucose, and with heparan sulphate and keratan sulphate. The major determinant of the chemical shift of the acetamido methyl resonance is the closeness of approach between carboxy groups and the acetamido group, in agreement with chemical evidence based on periodate-oxidation kinetics.", "contents": "1H nuclear-magnetic-resonance spectra of the methyl group of the acetamido moiety and the structure of acid glycosaminoglycans in solution. The 1H resonances of the methyl group in the acetamido moiety of several types of glycosaminoglycans are reported at 300 MHz in 2H2O. Dermatan sulphates with various L-iduronate/D-glucuronate ratios are compared with chrondroitin sulphates with various contents and positions of substitution of sulphate esters. Hyaluronate oligomers are compared with 2-acetamido-2-deoxy-D-glucose, and with heparan sulphate and keratan sulphate. The major determinant of the chemical shift of the acetamido methyl resonance is the closeness of approach between carboxy groups and the acetamido group, in agreement with chemical evidence based on periodate-oxidation kinetics."}
{"id": "PMID:227367", "title": "Metabolism and biological activity of 25-fluorocholecalciferol, 24-dehydrocholecalciferol and 25-dehydrocholecalciferol in the rat.", "content": "Three side-chain analogues of cholecalciferol (vitamin D3) modified at C-25, namely 25-fluorocholecalciferol, 24-dehydrocholecalciferol and 25-dehydrocholecalciferol, conceived as potential inhibitors of the cholecalciferol 25-hydroxylase have been prepared and tested in the rat. These compounds markedly diminish conversion in vivo of cholecalciferol into 25-hydroxycholecalciferol, but are not antagonists of vitamin D action, because they themselves possess significant biological activity in vivo. Each compound is capable of stimulating the intestinal transport of calcium and the mobilization of calcium from bone in vitamin D-deficient rats. Biological responses equivalent to those generated by a physiological dose of cholecalciferol (0.05 microgram) are produced, however, only when the analogues are administered at high doses (5-50 microgram). The biological activity of 24-dehydrocholecalciferol and 25-dehydrocholecalciferol is shown to result from conversion, in vivo, to the natural hormone, 1 alpha,25-dihydroxycholecalciferol, whereas 25-fluorocholecalciferol is metabolically activated in the rat by hydroxylation to 1 alpha-hydroxy-25-fluorocholecalciferol. This latter conversion is the first reported example of the 1 alpha-hydroxylation of a vitamin D compound lacking the 25-hydroxy group.", "contents": "Metabolism and biological activity of 25-fluorocholecalciferol, 24-dehydrocholecalciferol and 25-dehydrocholecalciferol in the rat. Three side-chain analogues of cholecalciferol (vitamin D3) modified at C-25, namely 25-fluorocholecalciferol, 24-dehydrocholecalciferol and 25-dehydrocholecalciferol, conceived as potential inhibitors of the cholecalciferol 25-hydroxylase have been prepared and tested in the rat. These compounds markedly diminish conversion in vivo of cholecalciferol into 25-hydroxycholecalciferol, but are not antagonists of vitamin D action, because they themselves possess significant biological activity in vivo. Each compound is capable of stimulating the intestinal transport of calcium and the mobilization of calcium from bone in vitamin D-deficient rats. Biological responses equivalent to those generated by a physiological dose of cholecalciferol (0.05 microgram) are produced, however, only when the analogues are administered at high doses (5-50 microgram). The biological activity of 24-dehydrocholecalciferol and 25-dehydrocholecalciferol is shown to result from conversion, in vivo, to the natural hormone, 1 alpha,25-dihydroxycholecalciferol, whereas 25-fluorocholecalciferol is metabolically activated in the rat by hydroxylation to 1 alpha-hydroxy-25-fluorocholecalciferol. This latter conversion is the first reported example of the 1 alpha-hydroxylation of a vitamin D compound lacking the 25-hydroxy group."}
{"id": "PMID:227368", "title": "Determination of vitamin D and its metabolites in plasma from normal and anephric man.", "content": "A multiple assay capable of reliably determining vitamins D(2) and D(3) (ergocalciferol and cholecalciferol), 25(OH)D(2) (25-hydroxyvitamin D(2)) and 25(OH)D(3) (25-hydroxyvitamin D(3)), 24,25(OH)(2)D (24,25-dihydroxyvitamin D), 25,26(OH)(2)D (25,26-dihydroxyvitamin D) and 1,25(OH)(2)D (1,25-dihydroxyvitamin D) in a single 3-5ml sample of human plasma was developed. The procedure involves methanol/methylene chloride extraction of plasma lipids followed by separation of the metabolites and purification from interfering contaminants by batch elution chromatography on Sephadex LH-20 and Lipidex 5000 and by h.p.l.c. (high-pressure liquid chromatography). Vitamins D(2) and D(3) and 25(OH)D(2) and 25(OH)D(3) are quantified by h.p.l.c. by using u.v. detection, comparing their peak heights with those of standards. 24,25(OH)(2)D and 25,26(OH)(2)D are measured by competitive protein-binding assay with diluted plasma from vitamin D-deficient rats. 1,25(OH)(2)D is measured by competitive protein-binding assay with diluted cytosol from vitamin D-deficient chick intestine. Values in normal human plasma samples taken in February are: vitamin D 3.5+/-2.5ng/ml; 25(OH)D 31.6+/-9.3ng/ml; 24,25(OH)(2)D 3.5+/-1.4ng/ml; 25,26(OH)(2)D 0.7+/-0.5ng/ml; 1,25(OH)(2)D 31+/-9pg/ml (means+/-s.d.). Values in two normal human plasma samples taken in February after 1 week of high sun exposure are: vitamin D 27.1+/-7.9ng/ml; 25(OH)D 56.8+/-4.2ng/ml; 24,25(OH)(2)D 4.3+/-1.6ng/ml; 25,26(OH)(2)D 0.5+/-0.2ng/ml. Values in anephric-human plasma are: vitamin D 2.7+/-0.8ng/ml; 25(OH)D 36.4+/-16.5ng/ml; 24,25(OH)(2)D 1.9+/-1.3ng/ml; 25,26(OH)(2)D 0.6+/-0.3ng/ml; 1,25(OH)(2)D was undetectable.", "contents": "Determination of vitamin D and its metabolites in plasma from normal and anephric man. A multiple assay capable of reliably determining vitamins D(2) and D(3) (ergocalciferol and cholecalciferol), 25(OH)D(2) (25-hydroxyvitamin D(2)) and 25(OH)D(3) (25-hydroxyvitamin D(3)), 24,25(OH)(2)D (24,25-dihydroxyvitamin D), 25,26(OH)(2)D (25,26-dihydroxyvitamin D) and 1,25(OH)(2)D (1,25-dihydroxyvitamin D) in a single 3-5ml sample of human plasma was developed. The procedure involves methanol/methylene chloride extraction of plasma lipids followed by separation of the metabolites and purification from interfering contaminants by batch elution chromatography on Sephadex LH-20 and Lipidex 5000 and by h.p.l.c. (high-pressure liquid chromatography). Vitamins D(2) and D(3) and 25(OH)D(2) and 25(OH)D(3) are quantified by h.p.l.c. by using u.v. detection, comparing their peak heights with those of standards. 24,25(OH)(2)D and 25,26(OH)(2)D are measured by competitive protein-binding assay with diluted plasma from vitamin D-deficient rats. 1,25(OH)(2)D is measured by competitive protein-binding assay with diluted cytosol from vitamin D-deficient chick intestine. Values in normal human plasma samples taken in February are: vitamin D 3.5+/-2.5ng/ml; 25(OH)D 31.6+/-9.3ng/ml; 24,25(OH)(2)D 3.5+/-1.4ng/ml; 25,26(OH)(2)D 0.7+/-0.5ng/ml; 1,25(OH)(2)D 31+/-9pg/ml (means+/-s.d.). Values in two normal human plasma samples taken in February after 1 week of high sun exposure are: vitamin D 27.1+/-7.9ng/ml; 25(OH)D 56.8+/-4.2ng/ml; 24,25(OH)(2)D 4.3+/-1.6ng/ml; 25,26(OH)(2)D 0.5+/-0.2ng/ml. Values in anephric-human plasma are: vitamin D 2.7+/-0.8ng/ml; 25(OH)D 36.4+/-16.5ng/ml; 24,25(OH)(2)D 1.9+/-1.3ng/ml; 25,26(OH)(2)D 0.6+/-0.3ng/ml; 1,25(OH)(2)D was undetectable."}
{"id": "PMID:227369", "title": "Effect of growth conditions on the involvement of cytochrome c in electron transport, proton translocation and ATP synthesis in the facultative methylotroph Pseudomonas AM1.", "content": "The stoicheiometry of proton translocation, the amounts of cytochromes firmly bound to membranes, and cell yields with respect to succinate and O(2) have been measured in the facultative methylotroph Pseudomonas AM1 and in the mutant lacking cytochrome c (mutant PCT76) during carbon-limited growth and carbon-excess growth. -->H(+)/O ratios during endogenous respiration of about 4 were measured in wild-type bacteria grown in carbon-excess conditions, and in the mutant in all growth conditions. During methanol- or succinate-limited growth of wild-type bacteria the -->H(+)/O ratio increased to about 6. Cell yields with respect to succinate and O(2) were higher in wild-type than in the mutant lacking cytochrome c by an amount suggesting loss in the mutant of 30% of the ATP-generating capacity of wild-type bacteria. During carbon-limited growth on methanol or succinate some cytochrome c was tightly bound to bacterial membranes, whereas none was tightly bound in bacteria grown in batch-culture or in NH(4) (+)-limited conditions. It is proposed that the role of cytochrome c in Pseudomonas AM1 depends on growth conditions and hence on the ;needs' of the bacteria. During growth in carbon-excess conditions it is only required for methanol oxidation, mediating between methanol dehydrogenase and cytochrome a/a(3). In these conditions oxidation of NADH and succinate by way of cytochrome b and cytochrome a/a(3) occurs without the mediation of cytochrome c. This is the only route for oxidation of NADH and succinate in the cytochrome c-deficient mutant in all growth conditions. During carbon-limited growth the cytochrome c becomes bound to the membrane in such a way that it can mediate between cytochromes b and a/a(3), hence becoming involved in proton translocation and ATP synthesis during NADH and succinate oxidation. An alternative possibility is that in wild-type bacteria the cytochrome c is always involved in electron transport, but that its involvement in measurable proton translocation only occurs in carbon-limited conditions.", "contents": "Effect of growth conditions on the involvement of cytochrome c in electron transport, proton translocation and ATP synthesis in the facultative methylotroph Pseudomonas AM1. The stoicheiometry of proton translocation, the amounts of cytochromes firmly bound to membranes, and cell yields with respect to succinate and O(2) have been measured in the facultative methylotroph Pseudomonas AM1 and in the mutant lacking cytochrome c (mutant PCT76) during carbon-limited growth and carbon-excess growth. -->H(+)/O ratios during endogenous respiration of about 4 were measured in wild-type bacteria grown in carbon-excess conditions, and in the mutant in all growth conditions. During methanol- or succinate-limited growth of wild-type bacteria the -->H(+)/O ratio increased to about 6. Cell yields with respect to succinate and O(2) were higher in wild-type than in the mutant lacking cytochrome c by an amount suggesting loss in the mutant of 30% of the ATP-generating capacity of wild-type bacteria. During carbon-limited growth on methanol or succinate some cytochrome c was tightly bound to bacterial membranes, whereas none was tightly bound in bacteria grown in batch-culture or in NH(4) (+)-limited conditions. It is proposed that the role of cytochrome c in Pseudomonas AM1 depends on growth conditions and hence on the ;needs' of the bacteria. During growth in carbon-excess conditions it is only required for methanol oxidation, mediating between methanol dehydrogenase and cytochrome a/a(3). In these conditions oxidation of NADH and succinate by way of cytochrome b and cytochrome a/a(3) occurs without the mediation of cytochrome c. This is the only route for oxidation of NADH and succinate in the cytochrome c-deficient mutant in all growth conditions. During carbon-limited growth the cytochrome c becomes bound to the membrane in such a way that it can mediate between cytochromes b and a/a(3), hence becoming involved in proton translocation and ATP synthesis during NADH and succinate oxidation. An alternative possibility is that in wild-type bacteria the cytochrome c is always involved in electron transport, but that its involvement in measurable proton translocation only occurs in carbon-limited conditions."}
{"id": "PMID:227370", "title": "Translation of embryonic-chick tendon procollagen messenger ribonucleic acid in two cell-free protein-synthesizing systems.", "content": "Embryonic-chick tendon poly(A)-containing RNA was translated in the wheat-germ and mRNA-dependent rabbit reticulocyte-lysate systems. The ability of each system to synthesize polypeptides similar to pro-alpha chains of collagen was tested on the bases of electrophoretic mobility and susceptibility to highly purified bacterial collagenase. Very small amounts of polypeptides in the size range of pro-alpha chains were synthesized in the wheat-germ system, whereas efficient synthesis of two polypeptides similar to pro-alpha1 and pro-alpha2 chains was achieved in the reticulocyte lysate. The collagenous nature of the major high-molecular-weight products synthesized was demonstrated by their susceptibility to collagenase and ability to act as a substrate for purified collagen proline hydroxylase. Determinations of the relative amounts of these translation products suggest that the 2:1 ratio of pro-alpha1 and pro-alpha2 chains found in type I procollagen is reflected in proportional amounts of translatable mRNA for pro-alpha1 and pro-alpha2 chains. Comparisons of the electrophoretic mobilities of hydroxylated and unhydroxylated reticulocyte-lysate translation products were made with appropriate standards of hydroxylated and unhydroxylated procollagen polypeptides. The results suggest that, in common with a number of secreted proteins, procollagen is synthesized as pre-pro molecules consistent with the ;Signal Hypothesis'.", "contents": "Translation of embryonic-chick tendon procollagen messenger ribonucleic acid in two cell-free protein-synthesizing systems. Embryonic-chick tendon poly(A)-containing RNA was translated in the wheat-germ and mRNA-dependent rabbit reticulocyte-lysate systems. The ability of each system to synthesize polypeptides similar to pro-alpha chains of collagen was tested on the bases of electrophoretic mobility and susceptibility to highly purified bacterial collagenase. Very small amounts of polypeptides in the size range of pro-alpha chains were synthesized in the wheat-germ system, whereas efficient synthesis of two polypeptides similar to pro-alpha1 and pro-alpha2 chains was achieved in the reticulocyte lysate. The collagenous nature of the major high-molecular-weight products synthesized was demonstrated by their susceptibility to collagenase and ability to act as a substrate for purified collagen proline hydroxylase. Determinations of the relative amounts of these translation products suggest that the 2:1 ratio of pro-alpha1 and pro-alpha2 chains found in type I procollagen is reflected in proportional amounts of translatable mRNA for pro-alpha1 and pro-alpha2 chains. Comparisons of the electrophoretic mobilities of hydroxylated and unhydroxylated reticulocyte-lysate translation products were made with appropriate standards of hydroxylated and unhydroxylated procollagen polypeptides. The results suggest that, in common with a number of secreted proteins, procollagen is synthesized as pre-pro molecules consistent with the ;Signal Hypothesis'."}
{"id": "PMID:227417", "title": "Ultrastructural examination of blood dialysate effect in experimental carbon monoxide poisoning of the heart muscle.", "content": "The effects of acute carbon monoxide poisoning on the ultrastructure of the muscle had been investigated. Dogs were exposed to 10.1 vol.% carbon monoxide by intracoronary perfusion for 10, 20 and 30 min. The ultrastructural changes and cytochrome-oxidase activity reduction were evident after 10 min and were most prominent after 20 and 30 min. Degenerative changes of mitochondria, pericapillary and interfibrillar edema, sarcoplasmic reticulum dilatation, glycogen content decrease and in local areas a total or partial necrosis of myofibrils could characteristically be observed. The cytochrome-oxidase and glycose-6-phosphate dehydrogenase showed a significant decrease. A dialysis concentrate from deproteinised calf blood (Solcoseryl, Actihaemyl) proved to inhibit morphological and enzymatical pathological changes; the destruction was slowed and prevented. On this basis the protective effect of Solcoseryl may be of considerable importance.", "contents": "Ultrastructural examination of blood dialysate effect in experimental carbon monoxide poisoning of the heart muscle. The effects of acute carbon monoxide poisoning on the ultrastructure of the muscle had been investigated. Dogs were exposed to 10.1 vol.% carbon monoxide by intracoronary perfusion for 10, 20 and 30 min. The ultrastructural changes and cytochrome-oxidase activity reduction were evident after 10 min and were most prominent after 20 and 30 min. Degenerative changes of mitochondria, pericapillary and interfibrillar edema, sarcoplasmic reticulum dilatation, glycogen content decrease and in local areas a total or partial necrosis of myofibrils could characteristically be observed. The cytochrome-oxidase and glycose-6-phosphate dehydrogenase showed a significant decrease. A dialysis concentrate from deproteinised calf blood (Solcoseryl, Actihaemyl) proved to inhibit morphological and enzymatical pathological changes; the destruction was slowed and prevented. On this basis the protective effect of Solcoseryl may be of considerable importance."}
{"id": "PMID:227418", "title": "Stimulatory effect of ginsenosides on DNA, protein and lipid synthesis in rat bone marrow and participation of cyclic nucleotides.", "content": "Effects of several kinds of ginsenosides, saponins from Panax ginseng on DNA, RNA, protein and lipid synthesis in bone marrow were investigated. Single i.p. injection of 0.5--1 mg/100 g body weight of ginsenosides Rb2, Rc, Re and Rg1 4 h prior to the sacrifice increased DNA synthesis in bone marrow cells. RNA, protein and lipid synthesis were also increased. The direct addition of ginsenosides Rb1, Rb2 and Rc mixture (GNS) enhanced DNA synthesis. Cyclic AMP levels in bone marrow cells were decreased 20 min after i.p. injection of ginsenosides Rb2, Rc and Rg1 and the direct addition of ginsenosides Rb2, Rc and Rg1 also decreased cyclic AMP levels. While cyclic GMP levels were increased by administration of ginsenosides Rb2, Re and Rg1. Relationship between chemical structure and actions of ginsenosides and the role of cyclic nucleotides in the stimulatory action of ginsenosides on DNA synthesis in bone marrow cells were discussed.", "contents": "Stimulatory effect of ginsenosides on DNA, protein and lipid synthesis in rat bone marrow and participation of cyclic nucleotides. Effects of several kinds of ginsenosides, saponins from Panax ginseng on DNA, RNA, protein and lipid synthesis in bone marrow were investigated. Single i.p. injection of 0.5--1 mg/100 g body weight of ginsenosides Rb2, Rc, Re and Rg1 4 h prior to the sacrifice increased DNA synthesis in bone marrow cells. RNA, protein and lipid synthesis were also increased. The direct addition of ginsenosides Rb1, Rb2 and Rc mixture (GNS) enhanced DNA synthesis. Cyclic AMP levels in bone marrow cells were decreased 20 min after i.p. injection of ginsenosides Rb2, Rc and Rg1 and the direct addition of ginsenosides Rb2, Rc and Rg1 also decreased cyclic AMP levels. While cyclic GMP levels were increased by administration of ginsenosides Rb2, Re and Rg1. Relationship between chemical structure and actions of ginsenosides and the role of cyclic nucleotides in the stimulatory action of ginsenosides on DNA synthesis in bone marrow cells were discussed."}
{"id": "PMID:227419", "title": "Further studies on the antipyretic action of polymyxin B in pyrogen-induced fever.", "content": "A study of the antipyretic effect of polymyxin B was undertaken to determine how this agent reduces fever in rabbits. It involved the effects of the drug: (1) on fever induced by exogenous pyrogenes (E. coli lipopolysaccharide, synthetic double-stranded ribonucleic acid, sodium nucleinate from yeast) and leucocytic pyrogen, (2) on the release of endogenous pyrogen in vivo and in vitro, and (3) on leucocytic and exogenous pyrogens in vitro. The results indicate that polymyxin B produces an antipyretic effect in endotoxin-induced fever primarily by an interaction of this cationic macromolecule with the anionic endotoxin molecule. Further it is likely that polymyxin B inhibits endogenous pyrogen synthesis and/or release from polymorphonuclear leucocytes.", "contents": "Further studies on the antipyretic action of polymyxin B in pyrogen-induced fever. A study of the antipyretic effect of polymyxin B was undertaken to determine how this agent reduces fever in rabbits. It involved the effects of the drug: (1) on fever induced by exogenous pyrogenes (E. coli lipopolysaccharide, synthetic double-stranded ribonucleic acid, sodium nucleinate from yeast) and leucocytic pyrogen, (2) on the release of endogenous pyrogen in vivo and in vitro, and (3) on leucocytic and exogenous pyrogens in vitro. The results indicate that polymyxin B produces an antipyretic effect in endotoxin-induced fever primarily by an interaction of this cationic macromolecule with the anionic endotoxin molecule. Further it is likely that polymyxin B inhibits endogenous pyrogen synthesis and/or release from polymorphonuclear leucocytes."}
{"id": "PMID:227420", "title": "[Effect of halofenate on triglyceride and uric acid levels, coagulation and platelet behaviour in patients with hyperlipoproteinemia type IV and hyperuricemia (author's transl)].", "content": "From experimental work, an influence of a drug with hypolipidemic and hypouricemic acition on blood coagulability and platelet function may be expected. Consequently, if these effects were demonstrable in man the drug could be assumed to reduce the tendency to develop thrombosis and atherosclerosis in patients with hyperlipidemia and hyperuricemia. In the study reported, the effect of 2-acetamidoethyl-(p-chlorophenyl)-(m-trifluoro-methylphenoxy)-acetate (halofenate) was investigated in 14 patients suffering from hyperlipoproteinemia type IV and hyperuricemia. Platelet aggregation and adhesiveness, plasma levels of triglycerides, cholesterol, uric acid, and clotting factors were regularly examined during a three-month double blind trial. While uric acid and triglyceride levels decreased, no influence of the drug treatment could be observed on platelet function and blood coagulability by the laboratory methods used.", "contents": "[Effect of halofenate on triglyceride and uric acid levels, coagulation and platelet behaviour in patients with hyperlipoproteinemia type IV and hyperuricemia (author's transl)]. From experimental work, an influence of a drug with hypolipidemic and hypouricemic acition on blood coagulability and platelet function may be expected. Consequently, if these effects were demonstrable in man the drug could be assumed to reduce the tendency to develop thrombosis and atherosclerosis in patients with hyperlipidemia and hyperuricemia. In the study reported, the effect of 2-acetamidoethyl-(p-chlorophenyl)-(m-trifluoro-methylphenoxy)-acetate (halofenate) was investigated in 14 patients suffering from hyperlipoproteinemia type IV and hyperuricemia. Platelet aggregation and adhesiveness, plasma levels of triglycerides, cholesterol, uric acid, and clotting factors were regularly examined during a three-month double blind trial. While uric acid and triglyceride levels decreased, no influence of the drug treatment could be observed on platelet function and blood coagulability by the laboratory methods used."}
{"id": "PMID:227421", "title": "Polymyxin B-induced oedema in hind paw of the rat as an assay for antiinflammatory drugs.", "content": "A method is presented for measuring the volume of the oedema induced by intraplantar infection of polymyxin B, a polyenic antibiotic, in the hind paw of the rat. Peak values of the oedema reached the maximum within 30 min to 1 h after injecting the drug and decreased with time until the 24th h, when it had almost disappeared. The phlogogenic effect of polymyxin B seems to be related to that induced by serotonin and histamine, rather than to the reaction provoked by carrageenin or prostaglandins. The oedema was inhibited by pretreating the animals p.o. with both steroidal and non-steroidal antiinflammatory agents. The inhibitory effect of antiinflammatory drugs was found to be dose-dependent.", "contents": "Polymyxin B-induced oedema in hind paw of the rat as an assay for antiinflammatory drugs. A method is presented for measuring the volume of the oedema induced by intraplantar infection of polymyxin B, a polyenic antibiotic, in the hind paw of the rat. Peak values of the oedema reached the maximum within 30 min to 1 h after injecting the drug and decreased with time until the 24th h, when it had almost disappeared. The phlogogenic effect of polymyxin B seems to be related to that induced by serotonin and histamine, rather than to the reaction provoked by carrageenin or prostaglandins. The oedema was inhibited by pretreating the animals p.o. with both steroidal and non-steroidal antiinflammatory agents. The inhibitory effect of antiinflammatory drugs was found to be dose-dependent."}
{"id": "PMID:227422", "title": "Activity of tolmetin on levels of cyclic nucleotides in experimental pleurisy.", "content": "Experimental pleurisy induced in rats with an intrapleural injection of 0.2 ml of 2% acetic acid, was used to test the effect of some non-steroidal anti-inflammatory drugs. During the acute phlogistic reaction there is a variation of the cAMP/cGMP ratio, with a sharp increase of the cGMP concentration and a parallel decrease of the cAMP level in the exudate. Indometacin and 1-methyl-5-p-toluoylpyrrole-2-acetic acid (tolmetin, Tolectin), two non-steroidal anti-inflammatory drugs, injected intrapleurally 1 h before the acetic acid injection were able to reduce the inflammatory response, affecting the cAMP and cGMP ratio. That is there is an increase of the cAMP level and a decrease of the cGMP level.", "contents": "Activity of tolmetin on levels of cyclic nucleotides in experimental pleurisy. Experimental pleurisy induced in rats with an intrapleural injection of 0.2 ml of 2% acetic acid, was used to test the effect of some non-steroidal anti-inflammatory drugs. During the acute phlogistic reaction there is a variation of the cAMP/cGMP ratio, with a sharp increase of the cGMP concentration and a parallel decrease of the cAMP level in the exudate. Indometacin and 1-methyl-5-p-toluoylpyrrole-2-acetic acid (tolmetin, Tolectin), two non-steroidal anti-inflammatory drugs, injected intrapleurally 1 h before the acetic acid injection were able to reduce the inflammatory response, affecting the cAMP and cGMP ratio. That is there is an increase of the cAMP level and a decrease of the cGMP level."}
{"id": "PMID:227423", "title": "Effect of 1,4-dimorpholino-7-(4-hydroxyphenyl)pyrido[3,4-d]) pyridazine [DS-511(4'-OH)] on the transepithelial transport of sodium and water and the permeability to urea in the toad urinary bladder.", "content": "To elucidate the mechanism of the inhibitory action of 1,4-dimorpholino-7-phenylpyrido[3,4-d]pyridazine (DS-511) on water and sodium reabsorption at the renal tubules, the effect of DS-511 (4'-OH), which is similar in diuretic effect to but more water-soluble than DS-511, on the transepithelial transport of sodium and water and permeability to urea was studied in isolated toad urinary bladder. Application of DS-511(4'-OH) at concentrations above 2 x 10(-4) mol/l to the serosal side of the bladder depressed the transepithelial potential difference, short circuit current (SCC), and membrane conductance as well as the increased response of the SCC to arginine vasopressin (AVP) and cyclic AMP. The effect of DS-511 (4'-OH) applied to the mucosal side was delayed in onset and less pronounced. Neither serosal nor mucosal 10(-3) mol/l DS-511(4'-OH) depressed the increased response of the SCC to amphotericin B. 2 x 10(-4) mol/l DS-511 (4'-OH) applied to the serosal side did not affect osmotic water flow, but potentiated the increase in water flow caused by AVP. Basal urea permeability as well as the increase in urea permeability caused by AVP were depressed by serosal 10(-3) mol/l DS-511 (4'-OH). The results show that DS-511(4'-OH) has two actions, the depression of the transepithelial transport of sodium and urea, and the potentiation of the increased water permeability caused by AVP.", "contents": "Effect of 1,4-dimorpholino-7-(4-hydroxyphenyl)pyrido[3,4-d]) pyridazine [DS-511(4'-OH)] on the transepithelial transport of sodium and water and the permeability to urea in the toad urinary bladder. To elucidate the mechanism of the inhibitory action of 1,4-dimorpholino-7-phenylpyrido[3,4-d]pyridazine (DS-511) on water and sodium reabsorption at the renal tubules, the effect of DS-511 (4'-OH), which is similar in diuretic effect to but more water-soluble than DS-511, on the transepithelial transport of sodium and water and permeability to urea was studied in isolated toad urinary bladder. Application of DS-511(4'-OH) at concentrations above 2 x 10(-4) mol/l to the serosal side of the bladder depressed the transepithelial potential difference, short circuit current (SCC), and membrane conductance as well as the increased response of the SCC to arginine vasopressin (AVP) and cyclic AMP. The effect of DS-511 (4'-OH) applied to the mucosal side was delayed in onset and less pronounced. Neither serosal nor mucosal 10(-3) mol/l DS-511(4'-OH) depressed the increased response of the SCC to amphotericin B. 2 x 10(-4) mol/l DS-511 (4'-OH) applied to the serosal side did not affect osmotic water flow, but potentiated the increase in water flow caused by AVP. Basal urea permeability as well as the increase in urea permeability caused by AVP were depressed by serosal 10(-3) mol/l DS-511 (4'-OH). The results show that DS-511(4'-OH) has two actions, the depression of the transepithelial transport of sodium and urea, and the potentiation of the increased water permeability caused by AVP."}
{"id": "PMID:227424", "title": "[The influence of pentifylline and theophylline on reaction kinetics on rat brain ATPase stimulatable by catecholamines (author's transl)].", "content": "The effects of 1-hexyl-3,7-dimethyl-xanthine (pentifylline, Cosaldon) and theophylline on rat brain Na+-, K+-, Mg2+ ATPase activities were investigated in in vitro experiments. It was established that pentifylline inhibits catecholamine sensitive ATPase in a dose dependent manner. Theophylline was without effect. Pentifylline also inhibited the Mg2+-dependent portion of Na+, K+-, Mg2+-ATPase. The effect of pentifylline on the kinetic parameters of Na+-, K+-, Mg2+-ATPase of synaptosomes was studied in detail. It was shown by a Lineweaver-Burk plot under the influence of pentifylline that the Michaelis constant (Km) increases from 1.0 x 10(-4) mol/l to 6.7 x 10(-4) mol/l. Km by norepinephrine stimulated ATPase decreases from 3.7 x 10(-4) mol/l to 2.9 x 10(-4) mol/l. In both experimental situations a decrease of maximal reaction velocity (Vmax) was observed. At high concentration of potassium in incubation medium the ATPase of synaptosomes was significantly more sensitive to pentifylline than at low concentration of potassium. The inhibition of ATPase by pentifylline was not influenced by the change in Na+/K+ ratio in the incubation medium. In all these experiments, theophylline used as a standard xanthine, was virtually without effect on the reaction kinetic of Na+-, K+-ATPase.", "contents": "[The influence of pentifylline and theophylline on reaction kinetics on rat brain ATPase stimulatable by catecholamines (author's transl)]. The effects of 1-hexyl-3,7-dimethyl-xanthine (pentifylline, Cosaldon) and theophylline on rat brain Na+-, K+-, Mg2+ ATPase activities were investigated in in vitro experiments. It was established that pentifylline inhibits catecholamine sensitive ATPase in a dose dependent manner. Theophylline was without effect. Pentifylline also inhibited the Mg2+-dependent portion of Na+, K+-, Mg2+-ATPase. The effect of pentifylline on the kinetic parameters of Na+-, K+-, Mg2+-ATPase of synaptosomes was studied in detail. It was shown by a Lineweaver-Burk plot under the influence of pentifylline that the Michaelis constant (Km) increases from 1.0 x 10(-4) mol/l to 6.7 x 10(-4) mol/l. Km by norepinephrine stimulated ATPase decreases from 3.7 x 10(-4) mol/l to 2.9 x 10(-4) mol/l. In both experimental situations a decrease of maximal reaction velocity (Vmax) was observed. At high concentration of potassium in incubation medium the ATPase of synaptosomes was significantly more sensitive to pentifylline than at low concentration of potassium. The inhibition of ATPase by pentifylline was not influenced by the change in Na+/K+ ratio in the incubation medium. In all these experiments, theophylline used as a standard xanthine, was virtually without effect on the reaction kinetic of Na+-, K+-ATPase."}
{"id": "PMID:227425", "title": "Studies on the mechanism of action of protacine (CR 604), a new non-steroidal anti-inflammatory agent.", "content": "3'-(4-[2-(1-P-Chlorobenzoyl-5-methoxy-2-methyl-indol-3-yl-acetoxy)-ethyl]-piperazin-1-yl)propyl-4-benzamido-N,N-dipropyl-glutaramate(+/-)dimaleate (protacine, CR 604), a new non-steroidal compound active on experimental inflammation, in vitro inhibits prostaglandin synthesis from arachidonic acid and platelet aggregation. When administered p.o., it prevents ex vivo platelet aggregation and in vivo arachidonate-induced thrombosis in rabbits. The cAMP levels of rat leucocytes are significantly reduced after treatment in vivo with protacine, even under maximum PGE-mediated stimulation. These effects, the inhibition of the proteolytic activity of trypsin and the fibrinolytic properties evidenced on recalcified plasma clots, contribute to explain the anti-inflammatory activity of protacine.", "contents": "Studies on the mechanism of action of protacine (CR 604), a new non-steroidal anti-inflammatory agent. 3'-(4-[2-(1-P-Chlorobenzoyl-5-methoxy-2-methyl-indol-3-yl-acetoxy)-ethyl]-piperazin-1-yl)propyl-4-benzamido-N,N-dipropyl-glutaramate(+/-)dimaleate (protacine, CR 604), a new non-steroidal compound active on experimental inflammation, in vitro inhibits prostaglandin synthesis from arachidonic acid and platelet aggregation. When administered p.o., it prevents ex vivo platelet aggregation and in vivo arachidonate-induced thrombosis in rabbits. The cAMP levels of rat leucocytes are significantly reduced after treatment in vivo with protacine, even under maximum PGE-mediated stimulation. These effects, the inhibition of the proteolytic activity of trypsin and the fibrinolytic properties evidenced on recalcified plasma clots, contribute to explain the anti-inflammatory activity of protacine."}
{"id": "PMID:227427", "title": "The effect of beta-pyridylcarbinol on lipoprotein lipids in primary type IIa hyperlipoproteinemia.", "content": "The effect of long-term treatment over 6 months with beta-pyridylcarbinol on the lipoprotein lipids was investigated in 12 patients with primary type IIa hyperlipoproteinemia. VLDL, LDL and HDL were separated by preparative ultracentrifugation. There was a significant decrease of serum cholesterol and phospholipids. The normal serum triglycerides were unaffected. While VLDL and HDL lipids showed no signicant alterations, the LDL lipids decreased. The atypical lipid composition of the LDL was changed towards normal. Though there was a significant decrease of the \"atherogenic\" LDL/HDL-lipid ratios after 6 months treatment, beta-pyridylcarbinol did not result in a normalization of this ratio.", "contents": "The effect of beta-pyridylcarbinol on lipoprotein lipids in primary type IIa hyperlipoproteinemia. The effect of long-term treatment over 6 months with beta-pyridylcarbinol on the lipoprotein lipids was investigated in 12 patients with primary type IIa hyperlipoproteinemia. VLDL, LDL and HDL were separated by preparative ultracentrifugation. There was a significant decrease of serum cholesterol and phospholipids. The normal serum triglycerides were unaffected. While VLDL and HDL lipids showed no signicant alterations, the LDL lipids decreased. The atypical lipid composition of the LDL was changed towards normal. Though there was a significant decrease of the \"atherogenic\" LDL/HDL-lipid ratios after 6 months treatment, beta-pyridylcarbinol did not result in a normalization of this ratio."}
{"id": "PMID:227428", "title": "Comparison of high density lipoprotein and serum cholesterol levels in a European and an African community.", "content": "Serum and high density lipoprotein cholesterol concentrations have been measured in 210 men and women in a London community and in a Nsukka community. Mean serum cholesterol concentrations were higher in London than in Nsukka. High density lipoprotein cholesterol was, however, higher in Nsukka than in London. Whereas the difference in serum cholesterol reached a statistical level when all the age groups were considered together, there was no statistical difference when the two populations were considered in terms of the young (20-39 year age group) and the middle aged (40-59 year age group). Difference in high density lipoprotein cholestrol, however, reached a statistical level in these two age groups.", "contents": "Comparison of high density lipoprotein and serum cholesterol levels in a European and an African community. Serum and high density lipoprotein cholesterol concentrations have been measured in 210 men and women in a London community and in a Nsukka community. Mean serum cholesterol concentrations were higher in London than in Nsukka. High density lipoprotein cholesterol was, however, higher in Nsukka than in London. Whereas the difference in serum cholesterol reached a statistical level when all the age groups were considered together, there was no statistical difference when the two populations were considered in terms of the young (20-39 year age group) and the middle aged (40-59 year age group). Difference in high density lipoprotein cholestrol, however, reached a statistical level in these two age groups."}
{"id": "PMID:227429", "title": "Familial type I hyperlipoproteinemia caused by apolipoprotein C-II deficiency.", "content": "A study was made on the clinical and biochemical features of siblings of patients with hyperchylomicronemia and its inherited relationship. It was not a case of the classical type of familial LPL deficiency, but of familial apolipoprotein C-II deficiency. The first patient with apolipoprotein C-II deficiency was reported by Breckenridge et al. and our patients provide the basis for the second report of this new disease. Our observations in this study strongly suggest that familial apolipoprotein C-II deficiency is transmitted by an autosomal recessive mode of inheritance and heterozygotes of this disorder have no abnormalities of plasma lipid and lipoproteins in spite of the reduced plasma apolipoprotein C-II.", "contents": "Familial type I hyperlipoproteinemia caused by apolipoprotein C-II deficiency. A study was made on the clinical and biochemical features of siblings of patients with hyperchylomicronemia and its inherited relationship. It was not a case of the classical type of familial LPL deficiency, but of familial apolipoprotein C-II deficiency. The first patient with apolipoprotein C-II deficiency was reported by Breckenridge et al. and our patients provide the basis for the second report of this new disease. Our observations in this study strongly suggest that familial apolipoprotein C-II deficiency is transmitted by an autosomal recessive mode of inheritance and heterozygotes of this disorder have no abnormalities of plasma lipid and lipoproteins in spite of the reduced plasma apolipoprotein C-II."}
{"id": "PMID:227430", "title": "Rate of exchange of esterified cholesterol between human plasma low and high density lipoproteins.", "content": "In vitro incubations of human low density lipoproteins (LDL), high density lipoproteins (HDL) and lipoprotein-free plasma at 37 degrees for 6 h revealed no significant net mass transfers of esterified cholesterol from either lipoprotein fraction to the other. Observed transfers of esterified [3H]cholesterol from LDL to HDL must, therefore, have represented a process of molecular exchange between the two fractions. The time course of the esterified [3H]cholesterol transfers indicated that, from the point of view of the exchange process, the pools of esterified cholesterol in LDL and HDL were (mathematically) homogeneous, thus permitting a precise calculation of the rate of the exchange between the two fractions. In incubations of lipoproteins isolated from the plasma of 9 clinically normal human subjects, there was an hourly exchange of 8-12% and 7-31% of the pools of esterified cholesterol in LDL and HDL respectively, which, in molar terms, represented an exchange of 108-301 mumol/l plasma/h between the two fractions. The exchange of esterified cholesterol between human LDL and HDL is, therefore, rapid when considered in relation to other parameters of esterified cholesterol and lipoprotein metabolism.", "contents": "Rate of exchange of esterified cholesterol between human plasma low and high density lipoproteins. In vitro incubations of human low density lipoproteins (LDL), high density lipoproteins (HDL) and lipoprotein-free plasma at 37 degrees for 6 h revealed no significant net mass transfers of esterified cholesterol from either lipoprotein fraction to the other. Observed transfers of esterified [3H]cholesterol from LDL to HDL must, therefore, have represented a process of molecular exchange between the two fractions. The time course of the esterified [3H]cholesterol transfers indicated that, from the point of view of the exchange process, the pools of esterified cholesterol in LDL and HDL were (mathematically) homogeneous, thus permitting a precise calculation of the rate of the exchange between the two fractions. In incubations of lipoproteins isolated from the plasma of 9 clinically normal human subjects, there was an hourly exchange of 8-12% and 7-31% of the pools of esterified cholesterol in LDL and HDL respectively, which, in molar terms, represented an exchange of 108-301 mumol/l plasma/h between the two fractions. The exchange of esterified cholesterol between human LDL and HDL is, therefore, rapid when considered in relation to other parameters of esterified cholesterol and lipoprotein metabolism."}
{"id": "PMID:227431", "title": "A longitudinal study of the biological variability of plasma lipoproteins in healthy young adults.", "content": "The fasting serum concentrations of total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), total triglyceride and apoprotein A1 were measured at intervals of 12-18 weeks for 60 weeks in 17 male and 11 female healthy young adults in order to assess the variability of these risk factors for coronary disease. No statistically significant seasonal changes were detected in any variable in either sex, although a progressive rise in apoprotein A1 concentration was observed. The coefficients of variation for random fluctuations with time were in the rank order: total cholesterol less than HDL-C less than apoprotein A1 less than LDL-C less than triglyceride. These differences were attributable to biological, rather than to methodological, factors. Within subjects, HDL cholesterol concentration varied inversely with triglyceride concentration and directly with apoprotein A1 concentration. The marked differences which exist in the biological variability of lipid risk factors for atherosclerosis need to be taken into account when making comparisons in epidemiological studies of the predictive powers of single on-entry measurements for future disease. Fluctuations of HDL-C with time appear to be related in part to variations in triglyceride-rich lipoprotein metabolism.", "contents": "A longitudinal study of the biological variability of plasma lipoproteins in healthy young adults. The fasting serum concentrations of total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), total triglyceride and apoprotein A1 were measured at intervals of 12-18 weeks for 60 weeks in 17 male and 11 female healthy young adults in order to assess the variability of these risk factors for coronary disease. No statistically significant seasonal changes were detected in any variable in either sex, although a progressive rise in apoprotein A1 concentration was observed. The coefficients of variation for random fluctuations with time were in the rank order: total cholesterol less than HDL-C less than apoprotein A1 less than LDL-C less than triglyceride. These differences were attributable to biological, rather than to methodological, factors. Within subjects, HDL cholesterol concentration varied inversely with triglyceride concentration and directly with apoprotein A1 concentration. The marked differences which exist in the biological variability of lipid risk factors for atherosclerosis need to be taken into account when making comparisons in epidemiological studies of the predictive powers of single on-entry measurements for future disease. Fluctuations of HDL-C with time appear to be related in part to variations in triglyceride-rich lipoprotein metabolism."}
{"id": "PMID:227432", "title": "Why very low density lipoprotein levels are normal in familial hyperchylomicronaemia.", "content": "The anomalous finding that very low density lipoprotein levels are relatively normal in patients with familial hyperchylomicronaemia has never been satisfactorily explained, particularly in view of the marked reduction or absence of peripheral lipoprotein lipase activity characteristic of this condition. I propose that the discrepancy between the plasma levels of the two triglyceride-rich lipoprotein fractions in these patients is due to the secretion by the liver of triglyceride in the form of chylomicron-like particles, rather than as very low density lipoprotein. The proposed \"switch\" in the spectrum of lipoproteins secreted by the liver is probably contingent upon the activity of the hepatic lipase present on the liver cell plasma membrane.", "contents": "Why very low density lipoprotein levels are normal in familial hyperchylomicronaemia. The anomalous finding that very low density lipoprotein levels are relatively normal in patients with familial hyperchylomicronaemia has never been satisfactorily explained, particularly in view of the marked reduction or absence of peripheral lipoprotein lipase activity characteristic of this condition. I propose that the discrepancy between the plasma levels of the two triglyceride-rich lipoprotein fractions in these patients is due to the secretion by the liver of triglyceride in the form of chylomicron-like particles, rather than as very low density lipoprotein. The proposed \"switch\" in the spectrum of lipoproteins secreted by the liver is probably contingent upon the activity of the hepatic lipase present on the liver cell plasma membrane."}
{"id": "PMID:227435", "title": "[A new method for determination of ATPase activity in tissue homogenates].", "content": "Authors describe a new method to determine Mg2+ and Na+K+ATPase activity on extremely small samples of tissue homogenates. They use specific inhibitors to discern between the two activities and a sensitive colorimetric method to dose Pi released from ATP, Lower limit of sensitivity is about 0,0100 micromoles of Pi/mg proteins/hour.", "contents": "[A new method for determination of ATPase activity in tissue homogenates]. Authors describe a new method to determine Mg2+ and Na+K+ATPase activity on extremely small samples of tissue homogenates. They use specific inhibitors to discern between the two activities and a sensitive colorimetric method to dose Pi released from ATP, Lower limit of sensitivity is about 0,0100 micromoles of Pi/mg proteins/hour."}
{"id": "PMID:227437", "title": "Effects of anaesthesia and surgery on plasma aldosterone concentration and renin activity in man.", "content": "The effects of various anaesthetic agents and surgery on the plasma concentrations of aldosterone and on renin activity were investigated in 76 patients. The plasma concentration of aldosterone was increased markedly by 2.5 times the control value during 45 min of ether anaesthesia. It was increased also during halothane, methoxyflurane and enflurane anaesthesia. Spinal anaesthesia did not alter significantly the plasma concentration of aldosterone. Plasma renin activity and ACTH concentration were increased slightly during general anaesthesia.", "contents": "Effects of anaesthesia and surgery on plasma aldosterone concentration and renin activity in man. The effects of various anaesthetic agents and surgery on the plasma concentrations of aldosterone and on renin activity were investigated in 76 patients. The plasma concentration of aldosterone was increased markedly by 2.5 times the control value during 45 min of ether anaesthesia. It was increased also during halothane, methoxyflurane and enflurane anaesthesia. Spinal anaesthesia did not alter significantly the plasma concentration of aldosterone. Plasma renin activity and ACTH concentration were increased slightly during general anaesthesia."}
{"id": "PMID:227441", "title": "Deoxyribonuclease activity found in Epstein--Barr virus producing lymphoblastoid cells.", "content": "A deoxyribonuclease activity from Epstein--Barr (EB) virus producer lymphocyte cell lines which is correlated with viral production and which is not present in virus non-producer or negative lymphocyte cell lines has been purified 220-fold with 20% recovery and characterized. This nuclease copurifies through diethylaminoethylcellulose column chromatography with the EB virus induced deoxyribonucleic acid (DNA) polymerase in EB virus producer cells which was recently reported by this laboratory, but elutes as a separate peak of activity upon phosphocellulose chromatography. This nuclease activity has a sedimentation coefficient of 4.0 S, a strong divalent cation requirement, an alkaline pH optimum, and the ability to utilize both native and denatured lymphocyte DNA as substrate, reducing both to monophosphonucleosides.", "contents": "Deoxyribonuclease activity found in Epstein--Barr virus producing lymphoblastoid cells. A deoxyribonuclease activity from Epstein--Barr (EB) virus producer lymphocyte cell lines which is correlated with viral production and which is not present in virus non-producer or negative lymphocyte cell lines has been purified 220-fold with 20% recovery and characterized. This nuclease copurifies through diethylaminoethylcellulose column chromatography with the EB virus induced deoxyribonucleic acid (DNA) polymerase in EB virus producer cells which was recently reported by this laboratory, but elutes as a separate peak of activity upon phosphocellulose chromatography. This nuclease activity has a sedimentation coefficient of 4.0 S, a strong divalent cation requirement, an alkaline pH optimum, and the ability to utilize both native and denatured lymphocyte DNA as substrate, reducing both to monophosphonucleosides."}
{"id": "PMID:227444", "title": "Stereochemistry of the hydrolysis of the endo isomer of uridine 2',3'-cyclic phosphorothioate catalyzed by the nonspecific phosphohydrolase from Enterobacter aerogenes.", "content": "The nonspecific phosphohydrolase from Enterobacter aerogenes (ATCC 13048) requires divalent metal ions for activity, since zinc present in the isolated enzyme can be removed by extensive dialysis against 8-hydroxyquinoline-5-sulfonate at pH 7.5 to yield an inactive enzyme which can be reactivated by addition of Zn2+, Cd2+, Co2+, Mn2+, or Ni2+; six ions of either zinc or cadmium can be incorporated into the inactive enzyme, and this incorporation of metal ion can be correlated with the regaining of activity (J. A. Gerlt, R. Dhesi, and H. C. Hemmings, unpublished experiments). The cadmium-reactivated phosphohydrolase catalyzes the hydrolysis of the endo isomer of uridine 2',3'-cyclic phosphorothioate (U greater than pS) to yield uridine 3'-monophosphorothioate as the major product. After enzymatic hydrolysis of the cyclic phosphorothioate in 19.8% H218O and chemical recyclization of the 18O-labeled acyclic phosphorothioates to yield a mixture of the endo and exo isomers of U greater than pS, 18O is found primarily in the exo isomer, as judged by examination of the 145.7-MHz phosphorus-31 nuclear magnetic resonance spectrum of the mixture. This observation indicates that the cadmium phosphosphohydrolase catalyzes hydrolysis of endo-U greater than pS with inversion of configuration, implying that the hydrolysis reaction proceeds by an in-line attack of water on the phosphorus.", "contents": "Stereochemistry of the hydrolysis of the endo isomer of uridine 2',3'-cyclic phosphorothioate catalyzed by the nonspecific phosphohydrolase from Enterobacter aerogenes. The nonspecific phosphohydrolase from Enterobacter aerogenes (ATCC 13048) requires divalent metal ions for activity, since zinc present in the isolated enzyme can be removed by extensive dialysis against 8-hydroxyquinoline-5-sulfonate at pH 7.5 to yield an inactive enzyme which can be reactivated by addition of Zn2+, Cd2+, Co2+, Mn2+, or Ni2+; six ions of either zinc or cadmium can be incorporated into the inactive enzyme, and this incorporation of metal ion can be correlated with the regaining of activity (J. A. Gerlt, R. Dhesi, and H. C. Hemmings, unpublished experiments). The cadmium-reactivated phosphohydrolase catalyzes the hydrolysis of the endo isomer of uridine 2',3'-cyclic phosphorothioate (U greater than pS) to yield uridine 3'-monophosphorothioate as the major product. After enzymatic hydrolysis of the cyclic phosphorothioate in 19.8% H218O and chemical recyclization of the 18O-labeled acyclic phosphorothioates to yield a mixture of the endo and exo isomers of U greater than pS, 18O is found primarily in the exo isomer, as judged by examination of the 145.7-MHz phosphorus-31 nuclear magnetic resonance spectrum of the mixture. This observation indicates that the cadmium phosphosphohydrolase catalyzes hydrolysis of endo-U greater than pS with inversion of configuration, implying that the hydrolysis reaction proceeds by an in-line attack of water on the phosphorus."}
{"id": "PMID:227445", "title": "Detergent inactivation of sodium- and potassium-activated adenosinetriphosphatase of the electric eel.", "content": "The stability of the sodium- and potassium-activated adenosinetriphosphatase (Na,K-ATPase) of the electric eel, Electrophorus electricus, was studied in five detergents in an effort to establish conditions for reconstitution of this membrane protein into defined phospholipids. The Na,K-ATPase activity of purified electric organ membranes as well as the ATPase is stable for at least 1 month of storage at 0 degrees C in the absence of detergents. At low concentrations of detergents, the enzyme is also stable for several days, but irreversible inactivation occurs rapidly as the detergent concentration is further increased. This inactivation begins at well-defined threshold concentrations for each detergent, and these concentrations generally occur in the order of the detergent critical micelle concentrations. Increasing the concentration of the electric organ membranes causes a linear increase in the inactivation threshold concentrations of Lubrol WX, deoxycholate, and cholate. The onset of inactivation evidently occurs when the mole fraction of detergent associated with the membrane lipids reaches a critical value in the narrow range of 0.2-0.4, in contrast to the large differences in the bulk concentrations of these detergents. The eel Na,K-ATPase is more sensitive to detergents than the sheep kidney enzyme.", "contents": "Detergent inactivation of sodium- and potassium-activated adenosinetriphosphatase of the electric eel. The stability of the sodium- and potassium-activated adenosinetriphosphatase (Na,K-ATPase) of the electric eel, Electrophorus electricus, was studied in five detergents in an effort to establish conditions for reconstitution of this membrane protein into defined phospholipids. The Na,K-ATPase activity of purified electric organ membranes as well as the ATPase is stable for at least 1 month of storage at 0 degrees C in the absence of detergents. At low concentrations of detergents, the enzyme is also stable for several days, but irreversible inactivation occurs rapidly as the detergent concentration is further increased. This inactivation begins at well-defined threshold concentrations for each detergent, and these concentrations generally occur in the order of the detergent critical micelle concentrations. Increasing the concentration of the electric organ membranes causes a linear increase in the inactivation threshold concentrations of Lubrol WX, deoxycholate, and cholate. The onset of inactivation evidently occurs when the mole fraction of detergent associated with the membrane lipids reaches a critical value in the narrow range of 0.2-0.4, in contrast to the large differences in the bulk concentrations of these detergents. The eel Na,K-ATPase is more sensitive to detergents than the sheep kidney enzyme."}
{"id": "PMID:227447", "title": "Density distribution, characterization, and comparative aspects of the major serum lipoproteins in the common marmoset (Callithrix jacchus), a New World primate with potential use in lipoprotein research.", "content": "Qualitative, quantitative, and comparative aspects of the serum lipoprotein profile in the Common marmoset (Callithrix jacchus), a New World primate, are described. Density gradient ultracentrifugation was used to evaluate lipoprotein distribution and to establish criteria for isolation of discrete molecular fractions. The major lipoprotein classes banded isopycnically on the gradient with the following hydrated densities: VLDL, d less than 1.017 g/mL; LDL, d = 1.027--1.055 g/mL; HDL fraction I, d = 1.070--1.127 g/mL; and HDL fraction II, d = 1.127--1.156 g/mL. Electrophoretic, immunological, and electron microscopic analyses attested to the purity of these fractions: the characteristics of each were assessed by chemical analysis, electron microscopy, immunological techniques, and polyacrylamide gel electrophoresis of their protein moieties. Marmoset VLDL and LDL were closely akin to those of man in size and chemical composition, although the former were richer in triglyceride; electrophoretic and immunological data showed the major protein component of VLDL and LDL to be a counterpart to human apo-B. The two HDL subfractions, i.e., HDL-I and HDL-II, corresponded in size and chemical composition to human HDL2 and HDL3, respectively, although slight differences in neutral lipid content were detected. By immunological and electrophoretic criteria, the major apolipoprotein of marmoset HDL was analogous to human apo-AI. In contrast, marked dissimilarities were evident in the complements of low molecular weight, tetramethylurea-soluble polypeptides of marmoset and human lipoproteins. Quantitatively, the human and marmoset lipoprotein profiles were not dissimilar, although HDL was the major class (approximately 50%); in fasting animals, serum concentrations of VLDL, LDL, and HDL were 50--90, 170--280, and 338--408 mg/dL, respectively. C. jacchus was distinct from man in displaying a greater proportion of its total HDL in the less dense (HDL-II) subfraction (marmoset HDL-I/HDL-II = approximately 4:1; human HDL2/HDL3 = approximately 1:3). These data indicate that, as an experimental animal for lipoprotein research, the Common marmoset combines the advantages of ready availability and maintenance with a serum lipoprotein profile which resembles, in many qualitative and quantitative aspects, that found in man.", "contents": "Density distribution, characterization, and comparative aspects of the major serum lipoproteins in the common marmoset (Callithrix jacchus), a New World primate with potential use in lipoprotein research. Qualitative, quantitative, and comparative aspects of the serum lipoprotein profile in the Common marmoset (Callithrix jacchus), a New World primate, are described. Density gradient ultracentrifugation was used to evaluate lipoprotein distribution and to establish criteria for isolation of discrete molecular fractions. The major lipoprotein classes banded isopycnically on the gradient with the following hydrated densities: VLDL, d less than 1.017 g/mL; LDL, d = 1.027--1.055 g/mL; HDL fraction I, d = 1.070--1.127 g/mL; and HDL fraction II, d = 1.127--1.156 g/mL. Electrophoretic, immunological, and electron microscopic analyses attested to the purity of these fractions: the characteristics of each were assessed by chemical analysis, electron microscopy, immunological techniques, and polyacrylamide gel electrophoresis of their protein moieties. Marmoset VLDL and LDL were closely akin to those of man in size and chemical composition, although the former were richer in triglyceride; electrophoretic and immunological data showed the major protein component of VLDL and LDL to be a counterpart to human apo-B. The two HDL subfractions, i.e., HDL-I and HDL-II, corresponded in size and chemical composition to human HDL2 and HDL3, respectively, although slight differences in neutral lipid content were detected. By immunological and electrophoretic criteria, the major apolipoprotein of marmoset HDL was analogous to human apo-AI. In contrast, marked dissimilarities were evident in the complements of low molecular weight, tetramethylurea-soluble polypeptides of marmoset and human lipoproteins. Quantitatively, the human and marmoset lipoprotein profiles were not dissimilar, although HDL was the major class (approximately 50%); in fasting animals, serum concentrations of VLDL, LDL, and HDL were 50--90, 170--280, and 338--408 mg/dL, respectively. C. jacchus was distinct from man in displaying a greater proportion of its total HDL in the less dense (HDL-II) subfraction (marmoset HDL-I/HDL-II = approximately 4:1; human HDL2/HDL3 = approximately 1:3). These data indicate that, as an experimental animal for lipoprotein research, the Common marmoset combines the advantages of ready availability and maintenance with a serum lipoprotein profile which resembles, in many qualitative and quantitative aspects, that found in man."}
{"id": "PMID:227452", "title": "Partial purification and characterization of a ribonucleic acid N2-guanine methyltransferase associated with avian myeloblastosis virus.", "content": "A nucleic acid methylase, N2-guanine ribonucleic acid (RNA) methyltransferase, which is associated with type C RNA tumor viruses, has been purified from avian myeloblastosis virions by gel filtration on Sephadex G-200, followed by chromatography on hydroxylapatite. The molecular weight estimated by gel filtration is 220 000, and the methylase activity has a pH optimum of 7.6--7.9. Magnesium and ammonium ions both stimulate activity 1.5-fold at 9.5 mM and 0.36 M, respectively, but apparently neither is essential for activity. Both daunomycin and adriamycin, antineoplastic drugs, also increase activity 1.5-fold at 1 mM. The enzyme was purified 120-fold from the virions and the activity is partially stabilized by dithiothretiol, but large losses were sustained during 24-h dialysis. The purified enzyme retains 75% of its activity on storage at -25 degrees C for 2 months in buffer containing 50% glycerol. Escherichia coli tRNAPhe and tRNAVal are preferred substrates with methylation occurring at position 10 of E. coli tRNAPhe.", "contents": "Partial purification and characterization of a ribonucleic acid N2-guanine methyltransferase associated with avian myeloblastosis virus. A nucleic acid methylase, N2-guanine ribonucleic acid (RNA) methyltransferase, which is associated with type C RNA tumor viruses, has been purified from avian myeloblastosis virions by gel filtration on Sephadex G-200, followed by chromatography on hydroxylapatite. The molecular weight estimated by gel filtration is 220 000, and the methylase activity has a pH optimum of 7.6--7.9. Magnesium and ammonium ions both stimulate activity 1.5-fold at 9.5 mM and 0.36 M, respectively, but apparently neither is essential for activity. Both daunomycin and adriamycin, antineoplastic drugs, also increase activity 1.5-fold at 1 mM. The enzyme was purified 120-fold from the virions and the activity is partially stabilized by dithiothretiol, but large losses were sustained during 24-h dialysis. The purified enzyme retains 75% of its activity on storage at -25 degrees C for 2 months in buffer containing 50% glycerol. Escherichia coli tRNAPhe and tRNAVal are preferred substrates with methylation occurring at position 10 of E. coli tRNAPhe."}
{"id": "PMID:227453", "title": "Purification and properties of the Ascaris pyruvate dehydrogenase complex.", "content": "The pyruvate dehyhdrogenase complex (pyruvate:lipoate oxidoreductase (decarboxylating and acceptor-acetylating), EC 1.2.4.1) has been isolated from Ascaris muscle mitochondria and purified to near homogeneity by differential centrifugation, (NH4)2SO4 fractionation and calcium phosphate gel-cellulose chromatography. It is similar in shape, size and physical characteristics to pyruvate dehydrogenase complexes isolated from mammalian sources. It has an absolute dependence on CoA, NAD+ and pyruvate for activity and is competitively inhibited by acetyl-CoA and NADH. However, much higher NADH/NAD+ ratios are necessary to inhibit activity, suggesting regulation by the more reduced state of the pyridine nucleotide pool in Ascaris mitochondria.", "contents": "Purification and properties of the Ascaris pyruvate dehydrogenase complex. The pyruvate dehyhdrogenase complex (pyruvate:lipoate oxidoreductase (decarboxylating and acceptor-acetylating), EC 1.2.4.1) has been isolated from Ascaris muscle mitochondria and purified to near homogeneity by differential centrifugation, (NH4)2SO4 fractionation and calcium phosphate gel-cellulose chromatography. It is similar in shape, size and physical characteristics to pyruvate dehydrogenase complexes isolated from mammalian sources. It has an absolute dependence on CoA, NAD+ and pyruvate for activity and is competitively inhibited by acetyl-CoA and NADH. However, much higher NADH/NAD+ ratios are necessary to inhibit activity, suggesting regulation by the more reduced state of the pyridine nucleotide pool in Ascaris mitochondria."}
{"id": "PMID:227455", "title": "Inhibition of (Na+ + K+)-ATPase by ouabain: involvement of calcium and membrane proteins.", "content": "Treatment of plasma membrane isolated from murine plasmocytoma MOPC 173 with an EDTA-containing buffer resulted in a 300-fold increase in sensitivity of (Na+ + K+)-stimulated Mg2+-ATPase to ouabain. This phenomenon was associated with the solubilization by EDTA of phospholipid free proteins (approx. 30 000-34 000 daltons) from the cytoplasmic face of the plasma membrane and with removal of about 90% of the membrane bound Ca2+. The recovery of the original resistance to ouabain required specifically Ca2+ and was associated with a binding of the solubilized proteins to the membrane.", "contents": "Inhibition of (Na+ + K+)-ATPase by ouabain: involvement of calcium and membrane proteins. Treatment of plasma membrane isolated from murine plasmocytoma MOPC 173 with an EDTA-containing buffer resulted in a 300-fold increase in sensitivity of (Na+ + K+)-stimulated Mg2+-ATPase to ouabain. This phenomenon was associated with the solubilization by EDTA of phospholipid free proteins (approx. 30 000-34 000 daltons) from the cytoplasmic face of the plasma membrane and with removal of about 90% of the membrane bound Ca2+. The recovery of the original resistance to ouabain required specifically Ca2+ and was associated with a binding of the solubilized proteins to the membrane."}
{"id": "PMID:227456", "title": "Contribution of villus and intervillus epithelium to intestinal transmural potential difference and response to theophylline and sugar.", "content": "A chamber design is described which permits isolation of villus or intervillus epithelium from proximal segments of Amphiuma intestine and measurement of the transpithelial potential difference (psi ms) and short-circuit current (Isc) produced by each. In media containing Cl- and 10 mequiv./l HCO3- the villus generated a basal psi ms of 0.8 mV (serosa negative) and Isc of 12 microA/cm2 while the intervillus psi ms and Isc were not different from zero. Acetazolamide altered the villus psi ms by 1.2 mV; the intervillus psi ms by only 0.3 mV. Transepithelial gradients of HCO3- appeared to generate diffusion potentials across the intervillus but not the villus epithelium. The actively transported sugar galactose elevated psi ms by 0.6 +/- 0.1 mV in the intervillus epithelium and by 1.5 +/- 0.2 mV in the villus epithelium for a response ratio (0.6/1.5) = 0.4. The response ratio for valine was 0.3. In contrast, the response ratios for theophylline (0.7) and cyclic AMP (0.7) were significantly higher. These observations indicate that the entire epithelium is responsive to theophylline and cyclic AMP while Na+-dependent solute transport and the basal electrogenic ion transport processes are primarily functions of the cells lining the intestinal villus.", "contents": "Contribution of villus and intervillus epithelium to intestinal transmural potential difference and response to theophylline and sugar. A chamber design is described which permits isolation of villus or intervillus epithelium from proximal segments of Amphiuma intestine and measurement of the transpithelial potential difference (psi ms) and short-circuit current (Isc) produced by each. In media containing Cl- and 10 mequiv./l HCO3- the villus generated a basal psi ms of 0.8 mV (serosa negative) and Isc of 12 microA/cm2 while the intervillus psi ms and Isc were not different from zero. Acetazolamide altered the villus psi ms by 1.2 mV; the intervillus psi ms by only 0.3 mV. Transepithelial gradients of HCO3- appeared to generate diffusion potentials across the intervillus but not the villus epithelium. The actively transported sugar galactose elevated psi ms by 0.6 +/- 0.1 mV in the intervillus epithelium and by 1.5 +/- 0.2 mV in the villus epithelium for a response ratio (0.6/1.5) = 0.4. The response ratio for valine was 0.3. In contrast, the response ratios for theophylline (0.7) and cyclic AMP (0.7) were significantly higher. These observations indicate that the entire epithelium is responsive to theophylline and cyclic AMP while Na+-dependent solute transport and the basal electrogenic ion transport processes are primarily functions of the cells lining the intestinal villus."}
{"id": "PMID:227457", "title": "Inhibition of ouabain-binding to (Na+ + K+)ATPase by antibody against the catalytic subunit but not by antibody against the glycoprotein subunit.", "content": "Antibodies against purified (Na+ + K+)ATPase from the rectal gland of Squalus acanthias, as well as against its catalytic subunit, inhibited ouabain binding by as much as 50%. However, antibodies against the glycoprotein subunit did not inhibit ouabain binding. These data suggest that binding of antibody against the catalytic subunit to the enzyme either covers the ouabain binding site or destroys its confirmation, while binding of antibody against the glycoprotein has no such effect.", "contents": "Inhibition of ouabain-binding to (Na+ + K+)ATPase by antibody against the catalytic subunit but not by antibody against the glycoprotein subunit. Antibodies against purified (Na+ + K+)ATPase from the rectal gland of Squalus acanthias, as well as against its catalytic subunit, inhibited ouabain binding by as much as 50%. However, antibodies against the glycoprotein subunit did not inhibit ouabain binding. These data suggest that binding of antibody against the catalytic subunit to the enzyme either covers the ouabain binding site or destroys its confirmation, while binding of antibody against the glycoprotein has no such effect."}
{"id": "PMID:227458", "title": "Effects of dibutyryl cyclic AMP on the transport of alpha-methyl-D-glucoside and alpha-aminoisobutyric acid in separated tubules and brush border membranes from rabbit kidney.", "content": "The effect of dibutyryl cyclic AMP on the transport of alpha-methyl-D-glucoside and alpha-aminoisobutyric acid in separated tubules and purified brush border membranes from rabbit kidney was investigated using a rapid filtration procedure. Dibutyryl cyclic AMP stimulated the uptake of alpha-methyl-D-glucoside and alpha-aminoisobutyric acid by separated renal tubules in agreement iwth prior studies utilizing renal slices (Rea, C. and Segal, S. (1973) Biochim. Biophys. Acta 311, 615--624; Weiss, I.W., Morgan, K. and Phang, J.M. (1972) J. Biol. Chem. 247, 760--764). However, in contrast to previous reports, no preincubation of the tissue with dibutyryl cyclic AMP was required for stimulation of transport to be manifest. Dibutyryl cyclic AMP stimulated oxygen consumption by separated tubules suggesting that stimulation of transport may occur by a linkage with renal oxidative metabolism. Dibutyryl cyclic AMP increased the uptake of alpha-aminoisobutyric acid into purified renal brush border membranes. However the uptakes of alpha-methyl-D-glucoside, proline, leucine and phosphate into brush border membranes were significantly inhibited.", "contents": "Effects of dibutyryl cyclic AMP on the transport of alpha-methyl-D-glucoside and alpha-aminoisobutyric acid in separated tubules and brush border membranes from rabbit kidney. The effect of dibutyryl cyclic AMP on the transport of alpha-methyl-D-glucoside and alpha-aminoisobutyric acid in separated tubules and purified brush border membranes from rabbit kidney was investigated using a rapid filtration procedure. Dibutyryl cyclic AMP stimulated the uptake of alpha-methyl-D-glucoside and alpha-aminoisobutyric acid by separated renal tubules in agreement iwth prior studies utilizing renal slices (Rea, C. and Segal, S. (1973) Biochim. Biophys. Acta 311, 615--624; Weiss, I.W., Morgan, K. and Phang, J.M. (1972) J. Biol. Chem. 247, 760--764). However, in contrast to previous reports, no preincubation of the tissue with dibutyryl cyclic AMP was required for stimulation of transport to be manifest. Dibutyryl cyclic AMP stimulated oxygen consumption by separated tubules suggesting that stimulation of transport may occur by a linkage with renal oxidative metabolism. Dibutyryl cyclic AMP increased the uptake of alpha-aminoisobutyric acid into purified renal brush border membranes. However the uptakes of alpha-methyl-D-glucoside, proline, leucine and phosphate into brush border membranes were significantly inhibited."}
{"id": "PMID:227459", "title": "A spin-label study of sciatic nerves from quaking, jimpy and trembler mice.", "content": "The spin labels, 5-nitroxide stearic acid and 16-nitroxide stearic acid were incorporated into whole sciatic nerves dissected from normal, quaking, jimpy and trembler mice. With 5-nitroxide stearic acid, we have studied the thermal variation of the maximal apparent coupling constant (T) between 0 degrees C and 50 degrees C. Within this range of temperatures, we obtained identical values of 2 T for nerves from normal and jimpy mice, whereas 2 T was smaller for nerves from quaking and trembler mice. With 16-nitroxide stearic acid, composite spectra were recorded, particularly in the high-field range. A line characteristic of myelin was clearly observed in the spectra of nerves from normal and jimpy mice; its intensity was somewhat less in nerves from quaking mice and much less in spectra from trembler mice. A shoulder in the principal highfield line of the spectrum is modified only with nerves from jimpy mice. The results agree well with those obtained by electron microscopy, which reveal normal myelination in nerves from jimpy mice, a slight modification of the myelin from those of quaking mice and a practically complete demyelination in peripheral nerves from trembler mice. However, the structure of the nerves of jimpy mice also seems to be modified at an, as yet, undetermined level.", "contents": "A spin-label study of sciatic nerves from quaking, jimpy and trembler mice. The spin labels, 5-nitroxide stearic acid and 16-nitroxide stearic acid were incorporated into whole sciatic nerves dissected from normal, quaking, jimpy and trembler mice. With 5-nitroxide stearic acid, we have studied the thermal variation of the maximal apparent coupling constant (T) between 0 degrees C and 50 degrees C. Within this range of temperatures, we obtained identical values of 2 T for nerves from normal and jimpy mice, whereas 2 T was smaller for nerves from quaking and trembler mice. With 16-nitroxide stearic acid, composite spectra were recorded, particularly in the high-field range. A line characteristic of myelin was clearly observed in the spectra of nerves from normal and jimpy mice; its intensity was somewhat less in nerves from quaking mice and much less in spectra from trembler mice. A shoulder in the principal highfield line of the spectrum is modified only with nerves from jimpy mice. The results agree well with those obtained by electron microscopy, which reveal normal myelination in nerves from jimpy mice, a slight modification of the myelin from those of quaking mice and a practically complete demyelination in peripheral nerves from trembler mice. However, the structure of the nerves of jimpy mice also seems to be modified at an, as yet, undetermined level."}
{"id": "PMID:227460", "title": "Effects of vanadate on ouabain binding and inhibition of (Na+ + K+)-ATPase.", "content": "Effects of vanadate on ouabain binding and inhibition of sodium and potassium adenosine triphosphatase (Na+ + K+)-ATPase) were investigated under various ionic conditions. 1. Vanadate facilitated ouabain binding to (Na+ + K+)-ATPase in the presence of Mg2+ and this facilitation was partially reversed by catechol. 2. Vanadate antagonized the ability of high concentrations of NaCl to inhibit ouabain binding in the presence of magnesium. 3. Ouabain binding to the vanadate-enzyme complex, formed from magnesium and vanadate, was more sensitive to depression by potassium than that to the phosphoenzyme formed from magnesium and inorganic phosphate. 4. Preincubation of (Na+ + K+)-ATPase with vanadate in the presence of magnesium initially formed a potassium-insensitive complex as shown by a rapid initial rate of ouabain binding. However, within 5 min potassium overcame the vanadate potentiation of ouabain binding regardless of the order in which it was added to the reaction mixture. 5. Under conditions of enzyme turnover, vanadate failed to antagonize the inhibitory power of ouabain despite the presence of a high concentration of potassium. This suggests a possible relationship between the sensitivity of the sodium pump in various tissues to the cardiac glycosides and intracellular vanadate concentrations.", "contents": "Effects of vanadate on ouabain binding and inhibition of (Na+ + K+)-ATPase. Effects of vanadate on ouabain binding and inhibition of sodium and potassium adenosine triphosphatase (Na+ + K+)-ATPase) were investigated under various ionic conditions. 1. Vanadate facilitated ouabain binding to (Na+ + K+)-ATPase in the presence of Mg2+ and this facilitation was partially reversed by catechol. 2. Vanadate antagonized the ability of high concentrations of NaCl to inhibit ouabain binding in the presence of magnesium. 3. Ouabain binding to the vanadate-enzyme complex, formed from magnesium and vanadate, was more sensitive to depression by potassium than that to the phosphoenzyme formed from magnesium and inorganic phosphate. 4. Preincubation of (Na+ + K+)-ATPase with vanadate in the presence of magnesium initially formed a potassium-insensitive complex as shown by a rapid initial rate of ouabain binding. However, within 5 min potassium overcame the vanadate potentiation of ouabain binding regardless of the order in which it was added to the reaction mixture. 5. Under conditions of enzyme turnover, vanadate failed to antagonize the inhibitory power of ouabain despite the presence of a high concentration of potassium. This suggests a possible relationship between the sensitivity of the sodium pump in various tissues to the cardiac glycosides and intracellular vanadate concentrations."}
{"id": "PMID:227461", "title": "Purification and characterization of DNA-relaxing enzyme from Haemophilus gallinarium.", "content": "A DNA-relaxing enzyme capable of concerted nicking and closing of DNA backbone bonds has been purified from Haemophilus gallinarum by two chromatographic steps and gel filtration. The enzyme efficiently catalyzes the removal of superhelical turns from a negatively twisted DNA and requires Mg2+ for this activity. Slight removal of superhelical turns from a positively twisted DNA generated by binding of ethidium bromide is found, but only at high enzyme concentrations. The DNA-relaxing activity is inhibited markedly with heat-denatured DNA, whereas native DNA and RNA have almost no affect on this activity.", "contents": "Purification and characterization of DNA-relaxing enzyme from Haemophilus gallinarium. A DNA-relaxing enzyme capable of concerted nicking and closing of DNA backbone bonds has been purified from Haemophilus gallinarum by two chromatographic steps and gel filtration. The enzyme efficiently catalyzes the removal of superhelical turns from a negatively twisted DNA and requires Mg2+ for this activity. Slight removal of superhelical turns from a positively twisted DNA generated by binding of ethidium bromide is found, but only at high enzyme concentrations. The DNA-relaxing activity is inhibited markedly with heat-denatured DNA, whereas native DNA and RNA have almost no affect on this activity."}
{"id": "PMID:227462", "title": "Differential and selective inhibition of cellular and herpes simplex virus DNA synthesis by arabinofuranosyladenine.", "content": "The influence of 9-beta-D-arabinofuranosyladenine (beta araAdo) and of its anomer 9-alpha-D-arabinofuranosyladenine (alpha araAdo) was studied in non-infected cells and cells infected with herpes simplex virus type 1 (HSV-1) and HSV type 2 (HSV-2). alpha AraAdo is a strong inhibitor of proliferation of non-infected cells. Multiplication of HSV-1 and HSV-2 is not affected at all by alpha araAdo, while their growth is strongly inhibited by beta araAdo. alpha AraAdo exerts no effect on the incorporation of dThd into HSV DNA, but blocks the incorporation into host cell DNA. Its anomer, beta araAdo, affects the incorporation rate of both the viral DNA system and the host cell DNA system (the latter one to a lesser extent). alpha AraAMP is incorporated into newly synthesized cellular DNA but not into HSV DNA. Enzymic studies relevant that alpha araATP has no effect on the HSV DNA polymerase system but a high inhibitory potency in the host cell DNA polymerase alpha system. The anomeric form, beta araATP, is a sensitive inhibitor of HSV DNA polymerase while the cellular DNA polymerases alpha and beta are more refractory.", "contents": "Differential and selective inhibition of cellular and herpes simplex virus DNA synthesis by arabinofuranosyladenine. The influence of 9-beta-D-arabinofuranosyladenine (beta araAdo) and of its anomer 9-alpha-D-arabinofuranosyladenine (alpha araAdo) was studied in non-infected cells and cells infected with herpes simplex virus type 1 (HSV-1) and HSV type 2 (HSV-2). alpha AraAdo is a strong inhibitor of proliferation of non-infected cells. Multiplication of HSV-1 and HSV-2 is not affected at all by alpha araAdo, while their growth is strongly inhibited by beta araAdo. alpha AraAdo exerts no effect on the incorporation of dThd into HSV DNA, but blocks the incorporation into host cell DNA. Its anomer, beta araAdo, affects the incorporation rate of both the viral DNA system and the host cell DNA system (the latter one to a lesser extent). alpha AraAMP is incorporated into newly synthesized cellular DNA but not into HSV DNA. Enzymic studies relevant that alpha araATP has no effect on the HSV DNA polymerase system but a high inhibitory potency in the host cell DNA polymerase alpha system. The anomeric form, beta araATP, is a sensitive inhibitor of HSV DNA polymerase while the cellular DNA polymerases alpha and beta are more refractory."}
{"id": "PMID:227463", "title": "Presence of protein at the termini of intracellular adenovirus type 5 DNA.", "content": "Adenovirus type 5 contains linear double-stranded DNA with protein covalently attached to the ends of the molecules. The presence of protein at the termini of intracellular viral DNA in adenovirus type 5-infected cells was investigated at different stages during the replication process. The intracellular viral DNA was isolated from the nuclei by lysis in 4 M guanidine hydrochloride. Electrophoresis on agarose gels of HsuI restriction enzyme fragments and sucrose gradient centrifugation were used to detect protein on intracellular viral DNA. After uncoating parental DNA still contains protein attached to the termini of the viral genome. Replicating and mature progeny viral DNA can also be isolated in the form of DNA-protein complexes. These complexes exhibit the same properties as the DNA-protein complex isolated from purified virions. These results suggest that the protein at the termini of intracellular viral DNA is identical to the protein attached to the 5'-ends of the DNA extracted from virions and that it is possibly involved in the replication of viral DNA.", "contents": "Presence of protein at the termini of intracellular adenovirus type 5 DNA. Adenovirus type 5 contains linear double-stranded DNA with protein covalently attached to the ends of the molecules. The presence of protein at the termini of intracellular viral DNA in adenovirus type 5-infected cells was investigated at different stages during the replication process. The intracellular viral DNA was isolated from the nuclei by lysis in 4 M guanidine hydrochloride. Electrophoresis on agarose gels of HsuI restriction enzyme fragments and sucrose gradient centrifugation were used to detect protein on intracellular viral DNA. After uncoating parental DNA still contains protein attached to the termini of the viral genome. Replicating and mature progeny viral DNA can also be isolated in the form of DNA-protein complexes. These complexes exhibit the same properties as the DNA-protein complex isolated from purified virions. These results suggest that the protein at the termini of intracellular viral DNA is identical to the protein attached to the 5'-ends of the DNA extracted from virions and that it is possibly involved in the replication of viral DNA."}
{"id": "PMID:227464", "title": "Inhibition of cytomegalovirus-stimulated human cell ornithine decarboxylase by alpha-difluoromethylornithine.", "content": "1. The relationship between synthesis of putrescine, human cytomegalovirus DNA synthesis, cell DNA synthesis, and human cytomegalovirus replication has been studied. 2. Stimulation of ornithine decarboxylase activity by shifting low serum-arrested whole human embryo cells to high serum medium is inhibited more than 99% by 2.5 mM DL-alpha-difluoromethylornithine. The addition of DL-alpha-difluoromethylornithine to human cells arrested in low serum and subsequently stimulated by the addition of fresh high serum-containing medium, causes a greater percent inhibition of ornithine decarboxylase activity than when the drug is added to growing human cells. 3. Increased ornithine decarboxylase activity produced by infection of low serum-arrested human cells was inhibited by 5.0 mM of DL-alpha-difluoromethylornithine. However, at a concentration of 5.0 mM, neither DL-alpha-methylornithine nor DL-alpha-difluoromethylornithine affected human cytomegalovirus growth or was toxic to these cells. These data suggest that the increased putrescine synthesis produced by infection is not required for virus replication. 4. The addition of 5.0 mM DL-alpha-difluoromethylornithine had no effect on human cytomegalovirus DNA synthesis or human cytomegalovirus-induced stimulation of cell DNA synthesis. However, 5.0 mM DL-alpha-difluoromethylornithine significantly reduced the stimulation of cell DNA synthesis caused by treatment with mock infecting fluid.", "contents": "Inhibition of cytomegalovirus-stimulated human cell ornithine decarboxylase by alpha-difluoromethylornithine. 1. The relationship between synthesis of putrescine, human cytomegalovirus DNA synthesis, cell DNA synthesis, and human cytomegalovirus replication has been studied. 2. Stimulation of ornithine decarboxylase activity by shifting low serum-arrested whole human embryo cells to high serum medium is inhibited more than 99% by 2.5 mM DL-alpha-difluoromethylornithine. The addition of DL-alpha-difluoromethylornithine to human cells arrested in low serum and subsequently stimulated by the addition of fresh high serum-containing medium, causes a greater percent inhibition of ornithine decarboxylase activity than when the drug is added to growing human cells. 3. Increased ornithine decarboxylase activity produced by infection of low serum-arrested human cells was inhibited by 5.0 mM of DL-alpha-difluoromethylornithine. However, at a concentration of 5.0 mM, neither DL-alpha-methylornithine nor DL-alpha-difluoromethylornithine affected human cytomegalovirus growth or was toxic to these cells. These data suggest that the increased putrescine synthesis produced by infection is not required for virus replication. 4. The addition of 5.0 mM DL-alpha-difluoromethylornithine had no effect on human cytomegalovirus DNA synthesis or human cytomegalovirus-induced stimulation of cell DNA synthesis. However, 5.0 mM DL-alpha-difluoromethylornithine significantly reduced the stimulation of cell DNA synthesis caused by treatment with mock infecting fluid."}
{"id": "PMID:227465", "title": "Synthesis of sugar-modified nucleoside 5'-triphosphates with partially purified nucleotide kinases from calf thymus.", "content": "The partial purification of some nucleoside monophosphate kinases (ATP:nucleosidemonophosphate phosphotransferases, EC 2.7.4.4) from calf thymus by chromatography on Blue Sepharose to remove interfering phosphatase activity is described. Their specificities towards nucleoside monophosphates modified in the sugar are investigated. Pyrimidine nucleoside monophosphate kinase is not very much affected by such modifications, whereas GMP kinase does not tolerate such alteration. The effect on AMP kinase is intermediate.", "contents": "Synthesis of sugar-modified nucleoside 5'-triphosphates with partially purified nucleotide kinases from calf thymus. The partial purification of some nucleoside monophosphate kinases (ATP:nucleosidemonophosphate phosphotransferases, EC 2.7.4.4) from calf thymus by chromatography on Blue Sepharose to remove interfering phosphatase activity is described. Their specificities towards nucleoside monophosphates modified in the sugar are investigated. Pyrimidine nucleoside monophosphate kinase is not very much affected by such modifications, whereas GMP kinase does not tolerate such alteration. The effect on AMP kinase is intermediate."}
{"id": "PMID:227466", "title": "Inhibitory effect of a lethal toxic fragment of staphylococcal alpha-toxin on cyclic AMP-dependent protein kinase activity.", "content": "The effect of a lethal toxic fragment of staphylococcal alpha-toxin on the activity of adenosine 3',5'-monophosphate(cyclic AMP)-dependent protein kinase was examined. 1. The lethal toxic fragment produced a dose-dependent decrease in both the binding of cyclic AMP to the regulatory subunit and phosphorylation activity of cyclic AMP-dependent protein kinase obtained from rabbit skeletal muscles up to a plateau at a 50% inhibitory effect. The decrease in the activity of protein kinase observed with low doses of the lethal toxic fragment (0.1 microM) resulted from a competitive inhibition, probably by its interaction with the cyclic AMP-binding site in the regulatory subunit molecule. 2. The effects of a lethal toxic fragment and epinephrine on the cyclic AMP level and protein kinase activity were investigated in the perfused rabbit heart slices. The lethal toxic fragment attenuated the stimulation of cyclic AMP-dependent protein kinase activity ratio by epinephrine. 3. It is suggested that the specific action of a lethal toxic fragment on the cellular membrane enzymes may be attributable to the inhibition of the cyclic AMP-dependent protein kinase activity.", "contents": "Inhibitory effect of a lethal toxic fragment of staphylococcal alpha-toxin on cyclic AMP-dependent protein kinase activity. The effect of a lethal toxic fragment of staphylococcal alpha-toxin on the activity of adenosine 3',5'-monophosphate(cyclic AMP)-dependent protein kinase was examined. 1. The lethal toxic fragment produced a dose-dependent decrease in both the binding of cyclic AMP to the regulatory subunit and phosphorylation activity of cyclic AMP-dependent protein kinase obtained from rabbit skeletal muscles up to a plateau at a 50% inhibitory effect. The decrease in the activity of protein kinase observed with low doses of the lethal toxic fragment (0.1 microM) resulted from a competitive inhibition, probably by its interaction with the cyclic AMP-binding site in the regulatory subunit molecule. 2. The effects of a lethal toxic fragment and epinephrine on the cyclic AMP level and protein kinase activity were investigated in the perfused rabbit heart slices. The lethal toxic fragment attenuated the stimulation of cyclic AMP-dependent protein kinase activity ratio by epinephrine. 3. It is suggested that the specific action of a lethal toxic fragment on the cellular membrane enzymes may be attributable to the inhibition of the cyclic AMP-dependent protein kinase activity."}
{"id": "PMID:227467", "title": "Properties of rat liver nuclear protein kinases.", "content": "Two cyclic nucleotide-independent protein kinases (ATP:protein phosphotransferase, EC 2.7.1.37) have been purified to homogeneity from rat liver nuclei. While these enzymes have many similar catalytic properties (preference for acid rather than basic proteins), they differ in molecular weight and subunit composition. Protein kinase NII will utilize ATP and GTP as phosphate donors while protein kinase NI will only effectively use ATP. Both enzymes reveal an unusual activation by Fe2+.", "contents": "Properties of rat liver nuclear protein kinases. Two cyclic nucleotide-independent protein kinases (ATP:protein phosphotransferase, EC 2.7.1.37) have been purified to homogeneity from rat liver nuclei. While these enzymes have many similar catalytic properties (preference for acid rather than basic proteins), they differ in molecular weight and subunit composition. Protein kinase NII will utilize ATP and GTP as phosphate donors while protein kinase NI will only effectively use ATP. Both enzymes reveal an unusual activation by Fe2+."}
{"id": "PMID:227468", "title": "Dephosphorylation of purine mononucleotides by alkaline phosphatases. Substrate specificity and inhibition patterns.", "content": "Three purine mononucleotides, adenosine-, inosine- and guanosine monophosphate, were used as substrates at pH 7.4 and at 10.4 for three alkaline phosphatases (orthophosphoric-monoester phosphohydrolase (acid optimum), EC 3.1.3.1) containing similar phosphate-binding serine groups at their esteratic sites. Substrate specificity was found for the enzymes from calf intestine and bovine liver. Alkaline phosphatase from Escherichia coli was nonspecific. A substrate-dependent and pronounced inhibition with the purine analogue 1,3-dimethyl xanthine was found for the enzymes from intestine and liver, but not for alkaline phosphatase from E. coli. A substrate-independent and pronounced inhibition was found for all three enzymes with the phosphomonoester p-nitrophenol phosphate as the inhibitor. Alkaline phosphatases may play an important role in the regulation of the intracellular content of purine mononucleotides.", "contents": "Dephosphorylation of purine mononucleotides by alkaline phosphatases. Substrate specificity and inhibition patterns. Three purine mononucleotides, adenosine-, inosine- and guanosine monophosphate, were used as substrates at pH 7.4 and at 10.4 for three alkaline phosphatases (orthophosphoric-monoester phosphohydrolase (acid optimum), EC 3.1.3.1) containing similar phosphate-binding serine groups at their esteratic sites. Substrate specificity was found for the enzymes from calf intestine and bovine liver. Alkaline phosphatase from Escherichia coli was nonspecific. A substrate-dependent and pronounced inhibition with the purine analogue 1,3-dimethyl xanthine was found for the enzymes from intestine and liver, but not for alkaline phosphatase from E. coli. A substrate-independent and pronounced inhibition was found for all three enzymes with the phosphomonoester p-nitrophenol phosphate as the inhibitor. Alkaline phosphatases may play an important role in the regulation of the intracellular content of purine mononucleotides."}
{"id": "PMID:227469", "title": "Isolation and identification of a small molecular weight inhibitor of cyclic nucleotide phosphodiesterase from bovine brain.", "content": "In a search for endogenous regulators for cyclic nucleotide phosphodiesterase (3':5'-cyclic-AMP 5'-nucleotidohydrolase, EC 3.1.4.17), we found that the ultrafiltrate of bovine brain homogenate contained a cyclic nucleotide phosphodiesterase inhibitor. The inhibitor-containing fraction was further purified by ion-exchange column chromatography and gel filtration chromatography. The purified inhibitor was found to be a small molecular weight compound which had a maximum absorption at 248 nm. This compound was identified by thin-layer chromatography and high-pressure liquid chromatography as hypoxanthine. We suggest that hypoxanthine may serve as an endogenous regulator for the hydrolysis of cyclic nucleotide by cyclic nucleotide phosphodiesterase.", "contents": "Isolation and identification of a small molecular weight inhibitor of cyclic nucleotide phosphodiesterase from bovine brain. In a search for endogenous regulators for cyclic nucleotide phosphodiesterase (3':5'-cyclic-AMP 5'-nucleotidohydrolase, EC 3.1.4.17), we found that the ultrafiltrate of bovine brain homogenate contained a cyclic nucleotide phosphodiesterase inhibitor. The inhibitor-containing fraction was further purified by ion-exchange column chromatography and gel filtration chromatography. The purified inhibitor was found to be a small molecular weight compound which had a maximum absorption at 248 nm. This compound was identified by thin-layer chromatography and high-pressure liquid chromatography as hypoxanthine. We suggest that hypoxanthine may serve as an endogenous regulator for the hydrolysis of cyclic nucleotide by cyclic nucleotide phosphodiesterase."}
{"id": "PMID:227470", "title": "Activation of cyclic AMP-dependent protein kinases in human gut adenocarcinoma (HT 29) cells in culture.", "content": "Vasoactive intestinal peptide, secretin, catecholamines and prostaglandin E1 stimulate the accumulation of cyclic AMP in HT 29 cells (see Laburthe, M. et al. (1978) Proc. Natl. Acad. Sci. U.S. 75, 2772-2775). In the present work maximal activation of protein kinases has been obtained at similar or even lower concentrations of the effectors. Maximal stimulation also requires a phosphodiesterase inhibitor. Type I and type II cyclic AMP-dependent protein kinases from basal and stimulated cells have been characterized by DEAE-Sepharose chromatography. Further identidication of the kinase has been carried out by gel electrophoresis and assay of the enzymes in the gel slabs. Comparison of the radioautography patterns of high speed supernatant lysate from basal and stimulated cells shows: First, that one type I and two type II cyclic AMP-dependent protein kinases plus one or two major and two minor cyclic AMP-independent protein kinases are present in HT 29 cells. Second, that all three holoenzymes are fully dissociated upon maximal stimulation, while the activity of the independent kinases appears unchanged.", "contents": "Activation of cyclic AMP-dependent protein kinases in human gut adenocarcinoma (HT 29) cells in culture. Vasoactive intestinal peptide, secretin, catecholamines and prostaglandin E1 stimulate the accumulation of cyclic AMP in HT 29 cells (see Laburthe, M. et al. (1978) Proc. Natl. Acad. Sci. U.S. 75, 2772-2775). In the present work maximal activation of protein kinases has been obtained at similar or even lower concentrations of the effectors. Maximal stimulation also requires a phosphodiesterase inhibitor. Type I and type II cyclic AMP-dependent protein kinases from basal and stimulated cells have been characterized by DEAE-Sepharose chromatography. Further identidication of the kinase has been carried out by gel electrophoresis and assay of the enzymes in the gel slabs. Comparison of the radioautography patterns of high speed supernatant lysate from basal and stimulated cells shows: First, that one type I and two type II cyclic AMP-dependent protein kinases plus one or two major and two minor cyclic AMP-independent protein kinases are present in HT 29 cells. Second, that all three holoenzymes are fully dissociated upon maximal stimulation, while the activity of the independent kinases appears unchanged."}
{"id": "PMID:227471", "title": "Iron binding proteins and influx of iron across the duodenal brush border. Evidence for specific lactotransferrin receptors in the human intestine.", "content": "The ability of a range of homologous transferrin-like proteins to donate iron to pieces of human duodenal mucosa, was examined with an in vitro incubation technique. In contrast to serum transferrin and ovotransferrin, only lactotransferrin was able to yield its iron to intestinal tissue, but in an autologous system this protein was unable to donate iron to human reticulocyte preparations. Studies with 125I-labelled lactotransferrin and lactotransferrin dual-labelled with 59Fe and 125I, indicated that the intact protein is excluded from entry into the enterocytes. The experiments suggest that iron may be transported across the brush border after delivery to specific protein binding sites at the cell surface.", "contents": "Iron binding proteins and influx of iron across the duodenal brush border. Evidence for specific lactotransferrin receptors in the human intestine. The ability of a range of homologous transferrin-like proteins to donate iron to pieces of human duodenal mucosa, was examined with an in vitro incubation technique. In contrast to serum transferrin and ovotransferrin, only lactotransferrin was able to yield its iron to intestinal tissue, but in an autologous system this protein was unable to donate iron to human reticulocyte preparations. Studies with 125I-labelled lactotransferrin and lactotransferrin dual-labelled with 59Fe and 125I, indicated that the intact protein is excluded from entry into the enterocytes. The experiments suggest that iron may be transported across the brush border after delivery to specific protein binding sites at the cell surface."}
{"id": "PMID:227472", "title": "Influence of plasma calcium and vitamin D on bone collagen. Effects on lysine hydroxylation and crosslink formation.", "content": "In chick bone collagen the degree of lysine hydroxylation and the magnitude of the crosslink ratio dihydroxylysinonorleucine/hydroxylysinonorleucine were both found to be inversely related to the concentration of plasma calcium. Lysine hydroxylation was also affected by a second factor related to vitamin D status.", "contents": "Influence of plasma calcium and vitamin D on bone collagen. Effects on lysine hydroxylation and crosslink formation. In chick bone collagen the degree of lysine hydroxylation and the magnitude of the crosslink ratio dihydroxylysinonorleucine/hydroxylysinonorleucine were both found to be inversely related to the concentration of plasma calcium. Lysine hydroxylation was also affected by a second factor related to vitamin D status."}
{"id": "PMID:227473", "title": "Increased number of beta-adrenergic receptors in the hypertrophied myocardium.", "content": "Development of cardiac hypertrophy is associated with depletion of endogenous catecholamine stores and increased inotropic response to exogenous catecholamines. A biochemical basis for these changes is provided by the observation that the number of cardiac beta-adrenergic receptors - as reflected in specific [3H]dihydroalprenolol binding - is increased in hypertrophy without a change in the affinity of dihydroalprenolol for the binding sites or in the capacity of isoproterenol to displace dihydroalprenolol. This change in beta-receptor numbers may be an important adaptive mechanism for preserving the contractile performance of the hypertrophied myocardium.", "contents": "Increased number of beta-adrenergic receptors in the hypertrophied myocardium. Development of cardiac hypertrophy is associated with depletion of endogenous catecholamine stores and increased inotropic response to exogenous catecholamines. A biochemical basis for these changes is provided by the observation that the number of cardiac beta-adrenergic receptors - as reflected in specific [3H]dihydroalprenolol binding - is increased in hypertrophy without a change in the affinity of dihydroalprenolol for the binding sites or in the capacity of isoproterenol to displace dihydroalprenolol. This change in beta-receptor numbers may be an important adaptive mechanism for preserving the contractile performance of the hypertrophied myocardium."}
{"id": "PMID:227474", "title": "Kinetic control of phosphoglycerate mutase from Flavobacterium sp. grown on ethylene glycol.", "content": "A species of Flavobacterium able to oxidise ethylene glycol to pyruvate via glyoxylate, glycerate, 2-phosphoglycerate and phosphoenolpyruvate exploits phosphoglycerate mutase to initiate gluconeogenesis. Partially purified phosphoglycerate mutase from this bacterium is independent of adenylate charge control but is activated by phosphoenolpyruvate. The possible significance of this regulation is discussed.", "contents": "Kinetic control of phosphoglycerate mutase from Flavobacterium sp. grown on ethylene glycol. A species of Flavobacterium able to oxidise ethylene glycol to pyruvate via glyoxylate, glycerate, 2-phosphoglycerate and phosphoenolpyruvate exploits phosphoglycerate mutase to initiate gluconeogenesis. Partially purified phosphoglycerate mutase from this bacterium is independent of adenylate charge control but is activated by phosphoenolpyruvate. The possible significance of this regulation is discussed."}
{"id": "PMID:227475", "title": "The nature of the hepatic receptors involved in vasopressin-induced glycogenolysis.", "content": "We have found a close correlation between the known vasopressor potency of arginine vasopressin and fourteen structural analogs, and the ability of these peptides to activate glycogen phosphorylase in isolated rat hepatocytes; there was no relation with the known antidiuretic activity of the analogs. We have also found that the pA2 values characterizing the known antivasopressor capacity of five analogs against vasopressin were close to those obtained for their inhibition of the vasopressin-induced activation of hepatic glycogen phosphorylase. We propose therefore that the hepatic receptors responsible for the glycogenolytic activity of vasopressin share characteristics with and appear therefore related to those responsible for pressor activity in vivo.", "contents": "The nature of the hepatic receptors involved in vasopressin-induced glycogenolysis. We have found a close correlation between the known vasopressor potency of arginine vasopressin and fourteen structural analogs, and the ability of these peptides to activate glycogen phosphorylase in isolated rat hepatocytes; there was no relation with the known antidiuretic activity of the analogs. We have also found that the pA2 values characterizing the known antivasopressor capacity of five analogs against vasopressin were close to those obtained for their inhibition of the vasopressin-induced activation of hepatic glycogen phosphorylase. We propose therefore that the hepatic receptors responsible for the glycogenolytic activity of vasopressin share characteristics with and appear therefore related to those responsible for pressor activity in vivo."}
{"id": "PMID:227476", "title": "The protein inhibitor of adenosine 3':5'-monophosphate-dependent protein kinases. Isolation and characterization of three isoinhibitors.", "content": "The protein inhibitor of adenosine 3':5 monophosphate-dependent protein-kinases has been purified from rabbit skeletal muscle by affinity chromatography on Sepharose-bound catalytic subunit of the kinase (Demaille et al. (1977) Biochemistry 16, 3080-3086). The inhibitory material can be separated into three species A, B and C either by polyacrylamide gel electrophoresis or by anion-exchange on DEAE-cellulose. However, the isoinhibitors display the same molecular weight and isoelectric point, and the same absence of acid-stable covalently bound phosphate. Their amino acid compositions are strikingly similar and their NH2-terminus are blocked. Also, their COOH-terminus appear to be very close to one another when studied by carboxypeptidase Y digestion. Their major difference lies in their inhibitory properties which are significantly weaker in inhibitor C (Ki = 0.87 nM) than in A and B (Ki = 0.18 and 0.23 nM, respectively). This is the first report on the existence of various forms of the protein-kinase inhibitor that exhibit different inhibitory properties and may play a role in the regulation of the protein-kinase system.", "contents": "The protein inhibitor of adenosine 3':5'-monophosphate-dependent protein kinases. Isolation and characterization of three isoinhibitors. The protein inhibitor of adenosine 3':5 monophosphate-dependent protein-kinases has been purified from rabbit skeletal muscle by affinity chromatography on Sepharose-bound catalytic subunit of the kinase (Demaille et al. (1977) Biochemistry 16, 3080-3086). The inhibitory material can be separated into three species A, B and C either by polyacrylamide gel electrophoresis or by anion-exchange on DEAE-cellulose. However, the isoinhibitors display the same molecular weight and isoelectric point, and the same absence of acid-stable covalently bound phosphate. Their amino acid compositions are strikingly similar and their NH2-terminus are blocked. Also, their COOH-terminus appear to be very close to one another when studied by carboxypeptidase Y digestion. Their major difference lies in their inhibitory properties which are significantly weaker in inhibitor C (Ki = 0.87 nM) than in A and B (Ki = 0.18 and 0.23 nM, respectively). This is the first report on the existence of various forms of the protein-kinase inhibitor that exhibit different inhibitory properties and may play a role in the regulation of the protein-kinase system."}
{"id": "PMID:227477", "title": "Oxidation-reduction potentials of the hemes in cytochrome C3 from Desulfovibrio gigas in the presence and absence of ferredoxin by EPR spectroscopy.", "content": "1. Ferricytochrome c3 from D. gigas exhibits two low-spin ferric heme EPR resonances with gz-values at 2.959 and 2.853. Ferrocytochrome c3 is diamagnetic based on the absence of any EPR signals. 2. EPR potentiometric titrations result in the resolution of the two low-spin ferric heme resonances into two additional heme components representing in total the four hemes of the cytochrome, with EM values of -235 mV and -315 mV at heme resonance I and EM values of -235 mV and -306 mV at heme resonance II. 3. EPR spectroscopy has detected a significant diminution of intensity (approx. 60 p. 100) in the gx amplitude of ferricytochrome c3 in the presence of D. gigas ferredoxin II. The presence of ferredoxin II also causes a more negative shift in the EM of the second components of the signals at heme resonances I and II of cytochrome C3. Both observations suggest that an interaction has occurred between cytochrome C3 and ferredoxin II. 4. The results presented suggest that the heme ligand environment of ferricytochrome c3 from D. gigas is less perturbed and/or less asymmetric than environment for ferricytochrome c3 from D. vulgaris whose EPR behavior indicates the non-equivalence of all four hemes.", "contents": "Oxidation-reduction potentials of the hemes in cytochrome C3 from Desulfovibrio gigas in the presence and absence of ferredoxin by EPR spectroscopy. 1. Ferricytochrome c3 from D. gigas exhibits two low-spin ferric heme EPR resonances with gz-values at 2.959 and 2.853. Ferrocytochrome c3 is diamagnetic based on the absence of any EPR signals. 2. EPR potentiometric titrations result in the resolution of the two low-spin ferric heme resonances into two additional heme components representing in total the four hemes of the cytochrome, with EM values of -235 mV and -315 mV at heme resonance I and EM values of -235 mV and -306 mV at heme resonance II. 3. EPR spectroscopy has detected a significant diminution of intensity (approx. 60 p. 100) in the gx amplitude of ferricytochrome c3 in the presence of D. gigas ferredoxin II. The presence of ferredoxin II also causes a more negative shift in the EM of the second components of the signals at heme resonances I and II of cytochrome C3. Both observations suggest that an interaction has occurred between cytochrome C3 and ferredoxin II. 4. The results presented suggest that the heme ligand environment of ferricytochrome c3 from D. gigas is less perturbed and/or less asymmetric than environment for ferricytochrome c3 from D. vulgaris whose EPR behavior indicates the non-equivalence of all four hemes."}
{"id": "PMID:227478", "title": "Chromatography of a Triton extracted beef cardiac cytochrome C1 preparation on diethylaminoethyl cellulose.", "content": "During the chromatography of a Triton X-100 extracted preparation of the mitochondrial membrane proteins on diethylaminoethyl cellulose, we have observed two chromatographic fractions containing cytochrome c1. One elutes from diethylaminoethyl cellulose with aqueous buffers alone, and the other elutes with those buffers after the addition of the nonionic detergent Triton X-100. The two forms occur in equimolar ratios and each retains its original chromatographic character on rechromatography, with no conversion of one form into the other.", "contents": "Chromatography of a Triton extracted beef cardiac cytochrome C1 preparation on diethylaminoethyl cellulose. During the chromatography of a Triton X-100 extracted preparation of the mitochondrial membrane proteins on diethylaminoethyl cellulose, we have observed two chromatographic fractions containing cytochrome c1. One elutes from diethylaminoethyl cellulose with aqueous buffers alone, and the other elutes with those buffers after the addition of the nonionic detergent Triton X-100. The two forms occur in equimolar ratios and each retains its original chromatographic character on rechromatography, with no conversion of one form into the other."}
{"id": "PMID:227480", "title": "Pattern generation in the lobster (Panulirus) stomatogastric ganglion. II. Pyloric network simulation.", "content": "1. Results from the companion paper were incorporated into a physiologically realistic computer model of the three principal cell types (PD/AB, LP, PY) of the pyloric network in the stomatogastric ganglion. Parameters for the model were mostly calculated (sometimes estimated) from experimental data rather than fitting the model to observed output patterns. 2. The initial run was successful in predicting several features of the pyloric pattern: the observed gap between PD and LP bursts, the appropriate sequence of the activity periods (PD, LP, PY), and a substantial PY burst not properly simulated by an earlier model. 3. The major discrepancy between model and observed patterns was the too-early occurrence of the PY burst, which resulted in a much shortened LP burst. Motivated by this discrepancy, additional investigations were made of PY properties. A hyperpolarization-enabled depolarization-activated hyperpolarizing conductance change was discovered which may make an important contribution to the late phase of PY activity in the normal burst cycle. Addition of this effect to the model brought its predictions more in line with observed patterns. 4. Other discrepancies between model and observation were instructive and are discussed. The findings force a substantial revision in previously held ideas on pattern production in the pyloric system. More weight must be given to functional properties of individual neurons and less to properties arising purely from network interactions. This shift in emphasis may be necessary in more complicated systems as well. 5. An example has been provided of the value quantitative modeling can be to network physiology. Only through rigorous quantitative testing can qualitative theories of how the nervous system operates be substantiated.", "contents": "Pattern generation in the lobster (Panulirus) stomatogastric ganglion. II. Pyloric network simulation. 1. Results from the companion paper were incorporated into a physiologically realistic computer model of the three principal cell types (PD/AB, LP, PY) of the pyloric network in the stomatogastric ganglion. Parameters for the model were mostly calculated (sometimes estimated) from experimental data rather than fitting the model to observed output patterns. 2. The initial run was successful in predicting several features of the pyloric pattern: the observed gap between PD and LP bursts, the appropriate sequence of the activity periods (PD, LP, PY), and a substantial PY burst not properly simulated by an earlier model. 3. The major discrepancy between model and observed patterns was the too-early occurrence of the PY burst, which resulted in a much shortened LP burst. Motivated by this discrepancy, additional investigations were made of PY properties. A hyperpolarization-enabled depolarization-activated hyperpolarizing conductance change was discovered which may make an important contribution to the late phase of PY activity in the normal burst cycle. Addition of this effect to the model brought its predictions more in line with observed patterns. 4. Other discrepancies between model and observation were instructive and are discussed. The findings force a substantial revision in previously held ideas on pattern production in the pyloric system. More weight must be given to functional properties of individual neurons and less to properties arising purely from network interactions. This shift in emphasis may be necessary in more complicated systems as well. 5. An example has been provided of the value quantitative modeling can be to network physiology. Only through rigorous quantitative testing can qualitative theories of how the nervous system operates be substantiated."}
{"id": "PMID:227481", "title": "[Electron carriers of adrenocortical mitochondria. Terminal systems].", "content": "A procedure for isolation of cytochrome oxidase and cytochrome P-450 from adrenocortical mitochondria was developed. The heme and copper contents, subunit composition, optical and EPR spectra for these enzymes were determined. The effects of pH, substrates and some inhibitors on the spectra of cytochrome P-450 were studied. It was found that cytochrome oxidase did not inhibit the reactions catalyzed by cytochrome P-450; cytochrome P-450 had no inhibiting effect on the oytochrome oxidase activity.", "contents": "[Electron carriers of adrenocortical mitochondria. Terminal systems]. A procedure for isolation of cytochrome oxidase and cytochrome P-450 from adrenocortical mitochondria was developed. The heme and copper contents, subunit composition, optical and EPR spectra for these enzymes were determined. The effects of pH, substrates and some inhibitors on the spectra of cytochrome P-450 were studied. It was found that cytochrome oxidase did not inhibit the reactions catalyzed by cytochrome P-450; cytochrome P-450 had no inhibiting effect on the oytochrome oxidase activity."}
{"id": "PMID:227482", "title": "[Electron acceptors in photosynthetic reaction centers from Rhodopseudomonas spheroides].", "content": "Using optical differential spectroscopy and EPR, a parallel study of light-induced electron transfer between the primary (X1) and secondary (X2) quinone-like acceptors in the preparations of reaction centers (RC) isolated from bacterial chromatophore membranes with sodium dodecyl sulfate was carried out. The data from direct measurements of the rate constant temperature dependence for the interaction between light-reduced X1 and X2 (KX1X2) are in good agreement with the data calculated from the kinetic analysis of dark reduction of photooxidized bacteriochlorophyll RC on the acceptors X1 and X2 (KX1X2 = 2.10(-1)S at 20 degrees; Ea = 11,8 kcal.mol-1 within the temperature range of 20 degrees-- -20 degrees). This evidence proves the efficiency of the previously used approach /1, 2/ for the evaluation of the X1-X2 interaction. The method proposed was used for a kinetic analysis of a low-temperature electron transfer from X1 to X2 in RC isolated with lauryldimethylaminoxide (KX1X2 = 2,3.10(2) S-1 at 20 degrees; Ea = 5,5 kcal.mol-1 within the temperature range of 10 degrees-- --70 degrees).", "contents": "[Electron acceptors in photosynthetic reaction centers from Rhodopseudomonas spheroides]. Using optical differential spectroscopy and EPR, a parallel study of light-induced electron transfer between the primary (X1) and secondary (X2) quinone-like acceptors in the preparations of reaction centers (RC) isolated from bacterial chromatophore membranes with sodium dodecyl sulfate was carried out. The data from direct measurements of the rate constant temperature dependence for the interaction between light-reduced X1 and X2 (KX1X2) are in good agreement with the data calculated from the kinetic analysis of dark reduction of photooxidized bacteriochlorophyll RC on the acceptors X1 and X2 (KX1X2 = 2.10(-1)S at 20 degrees; Ea = 11,8 kcal.mol-1 within the temperature range of 20 degrees-- -20 degrees). This evidence proves the efficiency of the previously used approach /1, 2/ for the evaluation of the X1-X2 interaction. The method proposed was used for a kinetic analysis of a low-temperature electron transfer from X1 to X2 in RC isolated with lauryldimethylaminoxide (KX1X2 = 2,3.10(2) S-1 at 20 degrees; Ea = 5,5 kcal.mol-1 within the temperature range of 10 degrees-- --70 degrees)."}
{"id": "PMID:227483", "title": "[Metlegoglobin reductase from lupine nodules. Purification and properties].", "content": "The purification procedure and properties of metlegoglobin reductase from the soluble fraction of lupine (Lupinus luteus L.) nodules and from the proteins secreted by bacteroids Rhizobium lupini in vitro are described. The properties of both forms of enzyme were found to be similar. A metlegoglobin reductase preparation purified 125-fold with a yield of 21% was obtained. The enzyme is strictly specific to the cofactor (NADH). No substrate specificity was revealed. The enzyme reduces oxidized cytochrome c, Mb+, Lb+, Hb+ and exygen. The pH optimum for the enzyme is 7,4. The enzyme is inhibited by p-chloromercurybenzoate. In some properties the enzyme from lupine nodules is close to methemoglobin reductase from the erythrocytes. It was shown that apart from metlegoglobin reductase, bacteroids secrete some other proteins, which is indicative of a close interrelationship between the bacteroids and the plant in a symbiotic nitrogen-fixing system.", "contents": "[Metlegoglobin reductase from lupine nodules. Purification and properties]. The purification procedure and properties of metlegoglobin reductase from the soluble fraction of lupine (Lupinus luteus L.) nodules and from the proteins secreted by bacteroids Rhizobium lupini in vitro are described. The properties of both forms of enzyme were found to be similar. A metlegoglobin reductase preparation purified 125-fold with a yield of 21% was obtained. The enzyme is strictly specific to the cofactor (NADH). No substrate specificity was revealed. The enzyme reduces oxidized cytochrome c, Mb+, Lb+, Hb+ and exygen. The pH optimum for the enzyme is 7,4. The enzyme is inhibited by p-chloromercurybenzoate. In some properties the enzyme from lupine nodules is close to methemoglobin reductase from the erythrocytes. It was shown that apart from metlegoglobin reductase, bacteroids secrete some other proteins, which is indicative of a close interrelationship between the bacteroids and the plant in a symbiotic nitrogen-fixing system."}
{"id": "PMID:227484", "title": "[Metabolic characteristics of prolyl hydroxylase].", "content": "The turnover time of prolyl hydroxylase in the skin of one-day-old rats treated in vivo with L-[14C]leucine is 22--34 hrs. Theoretically this time interval comprises two processes: i. e. incorporation of [14C]-Leu into the inactive enzyme precursor and transformation of the inactive from into the active enzyme.", "contents": "[Metabolic characteristics of prolyl hydroxylase]. The turnover time of prolyl hydroxylase in the skin of one-day-old rats treated in vivo with L-[14C]leucine is 22--34 hrs. Theoretically this time interval comprises two processes: i. e. incorporation of [14C]-Leu into the inactive enzyme precursor and transformation of the inactive from into the active enzyme."}
{"id": "PMID:227485", "title": "[Possible role of high molecular weight polyphosphates in ATP synthesis from exogenous adenine by the culture of Corynebacterium sp., strain VSTI-301].", "content": "An addition of exogenous adenine to an autolysing 72-hour culture of Corynebacterium sp., strain BSTI-301 results in accumulation of as much as 0,6--1,0 mp of ATP per 1 ml of medium. Extracellular ATP accumulation under such conditions is coupled with a considerable decrease of the intracellular content of 5'-phosphoribosyl-1-pyrophosphate, orthophosphate, pyrophosphate and two fractions of high-polymeric polyphosphates PPh3 and PPh4, as compared to the control. The activity of pyrophosphate phosphohydrolase (EC 3.6.1.1) and polyphosphate phosphohydrolase (EC 3.6.1.11) is thereby considerably decreased in the cells growing on exogenous adenine, while the activity of ADP-phosphotransferase (EC 2.7.4.1) is increased 2-fold. It was found that in experiments with 14C-adenine the intracellular content of both ATP and ADP remains unchanged despite a considerable accumulation of extracellular ATP in Corynebacterium sp., strain BSTI-301 cells.", "contents": "[Possible role of high molecular weight polyphosphates in ATP synthesis from exogenous adenine by the culture of Corynebacterium sp., strain VSTI-301]. An addition of exogenous adenine to an autolysing 72-hour culture of Corynebacterium sp., strain BSTI-301 results in accumulation of as much as 0,6--1,0 mp of ATP per 1 ml of medium. Extracellular ATP accumulation under such conditions is coupled with a considerable decrease of the intracellular content of 5'-phosphoribosyl-1-pyrophosphate, orthophosphate, pyrophosphate and two fractions of high-polymeric polyphosphates PPh3 and PPh4, as compared to the control. The activity of pyrophosphate phosphohydrolase (EC 3.6.1.1) and polyphosphate phosphohydrolase (EC 3.6.1.11) is thereby considerably decreased in the cells growing on exogenous adenine, while the activity of ADP-phosphotransferase (EC 2.7.4.1) is increased 2-fold. It was found that in experiments with 14C-adenine the intracellular content of both ATP and ADP remains unchanged despite a considerable accumulation of extracellular ATP in Corynebacterium sp., strain BSTI-301 cells."}
{"id": "PMID:227486", "title": "[Secondary structure and methylation of DNA in reinoculated tumors and cultures of embryonic cells transformed by oncogenic viruses].", "content": "Using the kinetic formaldehyde method the concentration of secondary structure defects (SSD) in the DNAs of ascite leukosis L 1210 cells and cultures of hamster embryonic cells transformed by virus SV-40 and polyoma was evaluated. It was found that this concentration was considerably higher than in the DNAs from normal liver and primary culture of mouse embryonic cells. The occurrence of the defects in malignant cell DNAs is not due to enzymatic degradation of DNA. Using thin-layer chromatography the content of m5C in the DNAs from 17 sources (transformed cell cultures, experimental tumours and liver cells of mouses with Ehrlich ascite carcinoma) were determined. The methylation level for all these DNAs was higher than for normal mouse and rat liver DNAs. No correlation between the SSD concentration and m5C content in the DNAs studied was observed.", "contents": "[Secondary structure and methylation of DNA in reinoculated tumors and cultures of embryonic cells transformed by oncogenic viruses]. Using the kinetic formaldehyde method the concentration of secondary structure defects (SSD) in the DNAs of ascite leukosis L 1210 cells and cultures of hamster embryonic cells transformed by virus SV-40 and polyoma was evaluated. It was found that this concentration was considerably higher than in the DNAs from normal liver and primary culture of mouse embryonic cells. The occurrence of the defects in malignant cell DNAs is not due to enzymatic degradation of DNA. Using thin-layer chromatography the content of m5C in the DNAs from 17 sources (transformed cell cultures, experimental tumours and liver cells of mouses with Ehrlich ascite carcinoma) were determined. The methylation level for all these DNAs was higher than for normal mouse and rat liver DNAs. No correlation between the SSD concentration and m5C content in the DNAs studied was observed."}
{"id": "PMID:227487", "title": "[Oxidation of 4-anilino-5-methoxydioxybenzene-1,2 in complex biochemical systems possessing superoxide dismutase activity].", "content": "The kinetics of 4-anilino-5-methoxydioxybenzene-1,2 (AMOBQH2) autoxidation in biochemical systems possessing the superoxide dismutase activity were studied. The autoxidation of AMOBQH2 is affected by superoxide dismutase, which is indicative of participation of the superoxide radical in this process. The main kinetic effect of superoxide dismutase consists in a decrease of the effective rate constant for AMOBQH2 autoxidation. Peroxidase releases the superoxide dismutase inhibition of AMOBQH2 autoxidation. The data obtained are discussed in terms of a biochemical mechanism of action of biologically active aminoaromatic derivatives of o-benzoquinone.", "contents": "[Oxidation of 4-anilino-5-methoxydioxybenzene-1,2 in complex biochemical systems possessing superoxide dismutase activity]. The kinetics of 4-anilino-5-methoxydioxybenzene-1,2 (AMOBQH2) autoxidation in biochemical systems possessing the superoxide dismutase activity were studied. The autoxidation of AMOBQH2 is affected by superoxide dismutase, which is indicative of participation of the superoxide radical in this process. The main kinetic effect of superoxide dismutase consists in a decrease of the effective rate constant for AMOBQH2 autoxidation. Peroxidase releases the superoxide dismutase inhibition of AMOBQH2 autoxidation. The data obtained are discussed in terms of a biochemical mechanism of action of biologically active aminoaromatic derivatives of o-benzoquinone."}
{"id": "PMID:227488", "title": "An automated analysis of REM sleep in primary depression.", "content": "The REM sleep of 23 nonpsychotic patients with primary depression was studied by means of an automated REM analyzer during a drug-free period and again during amitriptyline administration. Initial drug administration (50 mg) was associated with an immediate reduction in the number, average frequency, and average size of the rapid eye movements. The average REM size remained suppressed with continued drug administration while the average REM frequency showed a rebound which was responsible for a partial recovery of the number of REMs and total REM intensity to predrug levels. With regard to individual REM periods, REM frequency and REM intensity were redistributed during tricyclic administration so that the second REM period became more \"intense\" than the first REM period. This automated REM analysis technique provides an objective set of measures for characterizing discrete aspects of REM sleep during a depressive episode and for evaluating the changes in REM sleep during psychotropic trials.", "contents": "An automated analysis of REM sleep in primary depression. The REM sleep of 23 nonpsychotic patients with primary depression was studied by means of an automated REM analyzer during a drug-free period and again during amitriptyline administration. Initial drug administration (50 mg) was associated with an immediate reduction in the number, average frequency, and average size of the rapid eye movements. The average REM size remained suppressed with continued drug administration while the average REM frequency showed a rebound which was responsible for a partial recovery of the number of REMs and total REM intensity to predrug levels. With regard to individual REM periods, REM frequency and REM intensity were redistributed during tricyclic administration so that the second REM period became more \"intense\" than the first REM period. This automated REM analysis technique provides an objective set of measures for characterizing discrete aspects of REM sleep during a depressive episode and for evaluating the changes in REM sleep during psychotropic trials."}
{"id": "PMID:227489", "title": "Narcolepsy: a family study.", "content": "We obtained medical and psychological assessments and 48-hr polysomnographic recordings on five sisters, three of whom had narcolepsy. Of the three, two were identical twins. All three narcoleptic sisters cited emotional stress and environmental demands for sustained performance as the major factors which aggravated their symptoms, and corresponding to this, the illness followed a different life course in each of the three. Most striking were the differences between the twin sisters in clinical symptoms and polysomnographic signs. One sister suffered from all the symptoms of narcolepsy and her sleep recording showed the typical sleep onset REM periods of the disease. Her twin suffered only from excessive daytime drowsiness and her sleep recording was normal--at least by the usual criteria. The sleep of all three narcoleptic sisters, however, was significantly more fragmented than that of their normal siblings. Our data suggested that excessive sleep fragmentation was a basic feature of narcolepsy and that it betrayed a constitutional predisposition for sleep to dissociate into its components and to become distributed around the nycthemeron. This process could be aggravated by emotional stress and by environmental demands for sustained vigilance, and this in turn, created the differences in symptoms and signs between individuals with identical genetic predispositions.", "contents": "Narcolepsy: a family study. We obtained medical and psychological assessments and 48-hr polysomnographic recordings on five sisters, three of whom had narcolepsy. Of the three, two were identical twins. All three narcoleptic sisters cited emotional stress and environmental demands for sustained performance as the major factors which aggravated their symptoms, and corresponding to this, the illness followed a different life course in each of the three. Most striking were the differences between the twin sisters in clinical symptoms and polysomnographic signs. One sister suffered from all the symptoms of narcolepsy and her sleep recording showed the typical sleep onset REM periods of the disease. Her twin suffered only from excessive daytime drowsiness and her sleep recording was normal--at least by the usual criteria. The sleep of all three narcoleptic sisters, however, was significantly more fragmented than that of their normal siblings. Our data suggested that excessive sleep fragmentation was a basic feature of narcolepsy and that it betrayed a constitutional predisposition for sleep to dissociate into its components and to become distributed around the nycthemeron. This process could be aggravated by emotional stress and by environmental demands for sustained vigilance, and this in turn, created the differences in symptoms and signs between individuals with identical genetic predispositions."}
{"id": "PMID:227492", "title": "Preparation and properties of immobilized flavokinase.", "content": "Flavokinase (ATP: riboflavin 5'-phosphotransferase, EC 2.7.1.26) purified from rat liver by affinity chromatography, has been immobilized by amide linkage to omega-aminoalkyl-agarose beads. The immobilized enzyme differs from the soluble enzyme in having greater stability, slightly higher Km for the substrates, riboflavin and ATP, a broader pH optimum, and a lower energy of activation. These results suggest that the immobilized enzyme is influenced by the microenvironment of the bead and is subject to some degree of internal diffusional limitation. A small (3 ml), continuous, plug-flow reactor prepared with immobilized flavokinase effects 50% conversion of riboflavin to riboflavin 5'-phosphate (FMN) with a flow rate of 0.16 ml/min, which corresponds to an output of 5 nmol FMN/min. Immobilized flavokinase is effective for phosphorylating riboflavin and numerous riboflavin analogs and provides a facile method for preparing exclusively, unlike other synthetic methods, the 5'-phosphates.", "contents": "Preparation and properties of immobilized flavokinase. Flavokinase (ATP: riboflavin 5'-phosphotransferase, EC 2.7.1.26) purified from rat liver by affinity chromatography, has been immobilized by amide linkage to omega-aminoalkyl-agarose beads. The immobilized enzyme differs from the soluble enzyme in having greater stability, slightly higher Km for the substrates, riboflavin and ATP, a broader pH optimum, and a lower energy of activation. These results suggest that the immobilized enzyme is influenced by the microenvironment of the bead and is subject to some degree of internal diffusional limitation. A small (3 ml), continuous, plug-flow reactor prepared with immobilized flavokinase effects 50% conversion of riboflavin to riboflavin 5'-phosphate (FMN) with a flow rate of 0.16 ml/min, which corresponds to an output of 5 nmol FMN/min. Immobilized flavokinase is effective for phosphorylating riboflavin and numerous riboflavin analogs and provides a facile method for preparing exclusively, unlike other synthetic methods, the 5'-phosphates."}
{"id": "PMID:227493", "title": "[Reaction of nonmyelinated fibers of the cutaneous nerve of cats to cooling].", "content": "Combining the colliding impulses method with the methods of singling out the nerve's weak signals from the equipment noise shows that most nonmyelinated fibers of C1 and C2 groups develop impulses under cooling the cat hairy skin. In some nonmyelinated fibers of the C2 group there takes place an inhibition of spontaneous impulses in response to cooling.", "contents": "[Reaction of nonmyelinated fibers of the cutaneous nerve of cats to cooling]. Combining the colliding impulses method with the methods of singling out the nerve's weak signals from the equipment noise shows that most nonmyelinated fibers of C1 and C2 groups develop impulses under cooling the cat hairy skin. In some nonmyelinated fibers of the C2 group there takes place an inhibition of spontaneous impulses in response to cooling."}
{"id": "PMID:227494", "title": "[Effect of Vibrio cholerae filtrate on the adenyl cyclase system in vitro].", "content": "An in vitro model using homogenates of the rat intestine and liver for studying the V. Cholerae culture filtrate effect on the adenylate cyclase system is proposed. Optimal conditions for the adenylate cyclase functioning have been investigated for this model. It was shown that V. Cholerae filtrate induces a stable activation of adenylate cyclase and does not change the activity of cyclic AMP phosphodiesterase. It was also established that the activity of phosphodiesterase in the intestinal homogenate is about 2.5 fold higher than that in the liver homogenate. The model may be considered promising for investigation of the mechanism of cholerae toxin action.", "contents": "[Effect of Vibrio cholerae filtrate on the adenyl cyclase system in vitro]. An in vitro model using homogenates of the rat intestine and liver for studying the V. Cholerae culture filtrate effect on the adenylate cyclase system is proposed. Optimal conditions for the adenylate cyclase functioning have been investigated for this model. It was shown that V. Cholerae filtrate induces a stable activation of adenylate cyclase and does not change the activity of cyclic AMP phosphodiesterase. It was also established that the activity of phosphodiesterase in the intestinal homogenate is about 2.5 fold higher than that in the liver homogenate. The model may be considered promising for investigation of the mechanism of cholerae toxin action."}
{"id": "PMID:227495", "title": "[Thymic Kurloff inclusion. Action on the ovogenesis of the rat].", "content": "Grafts and injections of cellular extracts from thymus and spleen of guinea pigs, were carried out in puberal and impuberal female rats. These organs are especially rich in Foa-Kurloff cells after oestrogentherapy. Kidney served as a reference material for the same experimental conditions. Controls received cellular injections and grafts from guinea pig organs without treatment. In all cases, ovarian histological and biometric study of recipient animals shows no alteration of the ovarian cycle. On the other hand, grafts and injections of cellular extracts from organs with high concentration of Foa-Kurloff cells induced hyperactivity of internal theca folliculi and of ovarian interstitial cells, only in puberal female rats.", "contents": "[Thymic Kurloff inclusion. Action on the ovogenesis of the rat]. Grafts and injections of cellular extracts from thymus and spleen of guinea pigs, were carried out in puberal and impuberal female rats. These organs are especially rich in Foa-Kurloff cells after oestrogentherapy. Kidney served as a reference material for the same experimental conditions. Controls received cellular injections and grafts from guinea pig organs without treatment. In all cases, ovarian histological and biometric study of recipient animals shows no alteration of the ovarian cycle. On the other hand, grafts and injections of cellular extracts from organs with high concentration of Foa-Kurloff cells induced hyperactivity of internal theca folliculi and of ovarian interstitial cells, only in puberal female rats."}
{"id": "PMID:227501", "title": "Radiology of the adult sella turcica.", "content": "Radiographic changes of the sella turcica or pituitary fossa reflect multiple disease processes of intracranial, cranial and systemic origin. Their value as diagnostic aids is related to the fact that the development of the fossa depends somewhat upon that of the pituitary gland, which it partially encloses. Further, many vascular and neural structures about the base of the brain lie close to the fossa. Also, it is vulnerable to increased intracranial pressure. The ease of radiographic demonstration of the sellar components from many planes and angles allows early recognition of pathologic alterations. Radiographic anatomy, both normal and abnormal, will be discussed, as well special diagnostic procedures such as computed tomography, angiography and cerebral pneumography.", "contents": "Radiology of the adult sella turcica. Radiographic changes of the sella turcica or pituitary fossa reflect multiple disease processes of intracranial, cranial and systemic origin. Their value as diagnostic aids is related to the fact that the development of the fossa depends somewhat upon that of the pituitary gland, which it partially encloses. Further, many vascular and neural structures about the base of the brain lie close to the fossa. Also, it is vulnerable to increased intracranial pressure. The ease of radiographic demonstration of the sellar components from many planes and angles allows early recognition of pathologic alterations. Radiographic anatomy, both normal and abnormal, will be discussed, as well special diagnostic procedures such as computed tomography, angiography and cerebral pneumography."}
{"id": "PMID:227502", "title": "Heavy particle therapy: pituitary tumors.", "content": "Therapy with 910 MeV alpha particles provides a treatment with no mortality and an extremely low morbidity and has been highly successful in the control of pituitary hormone hypersecretion and tumor growth. It is possible to deliver radiation doses to the pituitary gland that are sufficiently high to inhibit or destroy the tumor cells that cause abnormal secretory activity without damaging the surrounding structures. The data demonstrate the effectiveness of this form of treatment in acromegaly, non-functioning pituitary tumors, prolactin secreting adenomas, Cushing's disease and Nelson's syndrome.", "contents": "Heavy particle therapy: pituitary tumors. Therapy with 910 MeV alpha particles provides a treatment with no mortality and an extremely low morbidity and has been highly successful in the control of pituitary hormone hypersecretion and tumor growth. It is possible to deliver radiation doses to the pituitary gland that are sufficiently high to inhibit or destroy the tumor cells that cause abnormal secretory activity without damaging the surrounding structures. The data demonstrate the effectiveness of this form of treatment in acromegaly, non-functioning pituitary tumors, prolactin secreting adenomas, Cushing's disease and Nelson's syndrome."}
{"id": "PMID:227503", "title": "Surgery of the pituitary gland.", "content": "Increasing diagnostic sophistication among endocrinologists has continually expanded the horizon of surgical treatment of adenohypophyseal problems. This advancement in endocrinology has been paralleled by improvement in the technical sophistication of neurosurgeons which has resulted in an increasingly aggressive approach to these serious disorders. Neurosurgical treatment is clearly able to provide resolution of significant physical disorders with minimal sequelae. The apparent potential for transsphenoidal approaches to the sella turcica as described within this paper has intrigued a number of neurosurgeons throughout this century. Their continuing interest has carried this procedure to a secure position in the management of many of these complex problems. This paper describes the author's experience with 132 consecutive transsphenoidal hypophysectomies.", "contents": "Surgery of the pituitary gland. Increasing diagnostic sophistication among endocrinologists has continually expanded the horizon of surgical treatment of adenohypophyseal problems. This advancement in endocrinology has been paralleled by improvement in the technical sophistication of neurosurgeons which has resulted in an increasingly aggressive approach to these serious disorders. Neurosurgical treatment is clearly able to provide resolution of significant physical disorders with minimal sequelae. The apparent potential for transsphenoidal approaches to the sella turcica as described within this paper has intrigued a number of neurosurgeons throughout this century. Their continuing interest has carried this procedure to a secure position in the management of many of these complex problems. This paper describes the author's experience with 132 consecutive transsphenoidal hypophysectomies."}
{"id": "PMID:227504", "title": "Clinical pituitary disorders.", "content": "The pituitary gland is really a confederation of several relatively independent endocrine glands gathered together in close relationship to the hypothalamus which exerts considerable governing control. Each of these sub-glands of the pituitary should be considered separately in every case of pituitary disease. While such an approach is mandatory in dealing with laboratory investigation, it also is profitable in considering clinical and therapeutic aspects of each case to ensure that nothing is overlooked.", "contents": "Clinical pituitary disorders. The pituitary gland is really a confederation of several relatively independent endocrine glands gathered together in close relationship to the hypothalamus which exerts considerable governing control. Each of these sub-glands of the pituitary should be considered separately in every case of pituitary disease. While such an approach is mandatory in dealing with laboratory investigation, it also is profitable in considering clinical and therapeutic aspects of each case to ensure that nothing is overlooked."}
{"id": "PMID:227505", "title": "Pathology of pituitary adenomas.", "content": "A new pituitary classification has been developed, based on the histologic, histochemical, immunocytologic and electron microscopic investigation of 207 pituitary adenomas removed surgically from male and female patients of various ages and different clinical symptomatology. Based principally on cytogenesis, the classification attempts to correlate the morphologic features of the tumor cells with their secretory activities, the clinical history, symptomatology, and biochemical findings. The classification consists of the following eight entities: 1) growth hormone cell adenoma; 2) prolactin cell adenoma; 3) mixed growth hormone cell-prolactin cell adenoma; 4) acidophil stem cell adenoma; 5) corticotroph cell adenoma; 6) thyrotroph cell adenoma; 7) gonadotroph cell adenoma; 8) undifferentiated cell adenoma, including oncocytoma. Prolactin adenomas were found to be the most frequently occurring pituitary adenoma type.", "contents": "Pathology of pituitary adenomas. A new pituitary classification has been developed, based on the histologic, histochemical, immunocytologic and electron microscopic investigation of 207 pituitary adenomas removed surgically from male and female patients of various ages and different clinical symptomatology. Based principally on cytogenesis, the classification attempts to correlate the morphologic features of the tumor cells with their secretory activities, the clinical history, symptomatology, and biochemical findings. The classification consists of the following eight entities: 1) growth hormone cell adenoma; 2) prolactin cell adenoma; 3) mixed growth hormone cell-prolactin cell adenoma; 4) acidophil stem cell adenoma; 5) corticotroph cell adenoma; 6) thyrotroph cell adenoma; 7) gonadotroph cell adenoma; 8) undifferentiated cell adenoma, including oncocytoma. Prolactin adenomas were found to be the most frequently occurring pituitary adenoma type."}
{"id": "PMID:227506", "title": "Investigation of the role of extracellular calcium in the control of acid secretion in the isolated whole stomach of the rat.", "content": "1 An isolated stomach preparation from immature rats has been used to study the role of extracellular calcium in the control of gastric acid secretion. Calcium was removed from both the serosal and mucosal solutions either in the absence of a chelating agent or in the presence of EGTA.2 Removal of calcium in the absence of EGTA had no significant effect on basal acid secretion or the acid responses to gastrin and dibutyryl cyclic adenosine 3',5'-monophosphate (db cyclic AMP). Under the same conditions there was a marked potentiation of the acid response to histamine, and a reduction of the acid response to acetylcholine which was readily reversed on restoring calcium to the bathing solutions.3 Removal of calcium in the presence of EGTA caused an inhibition of basal acid secretion and of the acid responses to histamine and db cyclic AMP. In each case this reduction in acid output was readily reversed on bathing the stomachs in normal calcium-containing (2.5 mM Ca(2+)) EGTA-free solutions.4 The inhibition of the acid response to histamine produced by Ca(2+)-free solutions which contained EGTA was not reversed on bathing the stomachs in solutions that contained both EGTA (0.1 mM) and an excess of calcium (2.5 mM).5 The removal of extracellular calcium in the absence of EGTA provided evidence that the secretion of H(+) ions is dependent under some conditions on calcium ions. The possibility cannot be excluded that EGTA itself exerts an inhibitory influence on the process of acid secretion.", "contents": "Investigation of the role of extracellular calcium in the control of acid secretion in the isolated whole stomach of the rat. 1 An isolated stomach preparation from immature rats has been used to study the role of extracellular calcium in the control of gastric acid secretion. Calcium was removed from both the serosal and mucosal solutions either in the absence of a chelating agent or in the presence of EGTA.2 Removal of calcium in the absence of EGTA had no significant effect on basal acid secretion or the acid responses to gastrin and dibutyryl cyclic adenosine 3',5'-monophosphate (db cyclic AMP). Under the same conditions there was a marked potentiation of the acid response to histamine, and a reduction of the acid response to acetylcholine which was readily reversed on restoring calcium to the bathing solutions.3 Removal of calcium in the presence of EGTA caused an inhibition of basal acid secretion and of the acid responses to histamine and db cyclic AMP. In each case this reduction in acid output was readily reversed on bathing the stomachs in normal calcium-containing (2.5 mM Ca(2+)) EGTA-free solutions.4 The inhibition of the acid response to histamine produced by Ca(2+)-free solutions which contained EGTA was not reversed on bathing the stomachs in solutions that contained both EGTA (0.1 mM) and an excess of calcium (2.5 mM).5 The removal of extracellular calcium in the absence of EGTA provided evidence that the secretion of H(+) ions is dependent under some conditions on calcium ions. The possibility cannot be excluded that EGTA itself exerts an inhibitory influence on the process of acid secretion."}
{"id": "PMID:227507", "title": "The effects of calcium and magnesium ions, temperature and repetitive stimulation on inhibitory junctional transmission in smooth muscle of guinea-pig small intestine.", "content": "1 The effects of calcium and magnesium ions and temperature on the peak amplitude of the nonadrenergic, noncholinergic inhibitory junction potential, evoked by a single stimulus, or paired transmural stimuli, were examined in the circular muscle of guinea-pig small intestine.2 The peak amplitude of the inhibitory junction potential (i.j.p.) could be decreased by lowering the external concentration of calcium or by raising the external magnesium concentration (at 25 degrees C).3 At 25 degrees C, the second of a pair of i.j.ps was larger than the first at short intervals (<0.2 s), but smaller at larger intervals (0.2 to 20 s). Enhancement of the second (test) response decayed exponentially with a time constant of 87 ms. Depression of the test i.j.p. was maximal at 0.4 s and then recovered exponentially with a time constant of 11 s.4 In low calcium or high magnesium solution, depression of the test i.j.p. decreased without any change in the rate of recovery from depression.5 Despite the slow rate of recovery from depression after a single conditioning response, transmitter output could be maintained during low-frequency repetitive stimulation.6 The peak amplitude of the i.j.p. increased as the temperature was raised to 35 degrees C (Q(10) = 1.5).7 In contrast to the neuromuscular junction, the depression of the second of a pair of i.j.ps decreased as the temperature was raised. At 35 degrees C the test i.j.p. was larger than the conditioning i.j.p. for most stimulus intervals (1 to 20 s).8 The results suggest that the rate of replenishment of the store of inhibitory transmitter is sensitive to both temperature and repetitive stimulation.", "contents": "The effects of calcium and magnesium ions, temperature and repetitive stimulation on inhibitory junctional transmission in smooth muscle of guinea-pig small intestine. 1 The effects of calcium and magnesium ions and temperature on the peak amplitude of the nonadrenergic, noncholinergic inhibitory junction potential, evoked by a single stimulus, or paired transmural stimuli, were examined in the circular muscle of guinea-pig small intestine.2 The peak amplitude of the inhibitory junction potential (i.j.p.) could be decreased by lowering the external concentration of calcium or by raising the external magnesium concentration (at 25 degrees C).3 At 25 degrees C, the second of a pair of i.j.ps was larger than the first at short intervals (<0.2 s), but smaller at larger intervals (0.2 to 20 s). Enhancement of the second (test) response decayed exponentially with a time constant of 87 ms. Depression of the test i.j.p. was maximal at 0.4 s and then recovered exponentially with a time constant of 11 s.4 In low calcium or high magnesium solution, depression of the test i.j.p. decreased without any change in the rate of recovery from depression.5 Despite the slow rate of recovery from depression after a single conditioning response, transmitter output could be maintained during low-frequency repetitive stimulation.6 The peak amplitude of the i.j.p. increased as the temperature was raised to 35 degrees C (Q(10) = 1.5).7 In contrast to the neuromuscular junction, the depression of the second of a pair of i.j.ps decreased as the temperature was raised. At 35 degrees C the test i.j.p. was larger than the conditioning i.j.p. for most stimulus intervals (1 to 20 s).8 The results suggest that the rate of replenishment of the store of inhibitory transmitter is sensitive to both temperature and repetitive stimulation."}
{"id": "PMID:227508", "title": "Naloxone reverses the antihypertensive effect of clonidine.", "content": "In unanesthetized, spontaneously hypertensive rats the decrease in blood pressure and heart rate produced by intravenous clonidine, 5 to 20 micrograms/kg, was inhibited or reversed by nalozone, 0.2 to 2 mg/kg. The hypotensive effect of 100 mg/kg alpha-methyldopa was also partially reversed by naloxone. Naloxone alone did not affect either blood pressure or heart rate. In brain membranes from spontaneously hypertensive rats clonidine, 10(-8) to 10(-5) M, did not influence stereoselective binding of [3H]-naloxone (8 nM), and naloxone, 10(-8) to 10(-4) M, did not influence clonidine-suppressible binding of [3H]-dihydroergocryptine (1 nM). These findings indicate that in spontaneously hypertensive rats the effects of central alpha-adrenoceptor stimulation involve activation of opiate receptors. As naloxone and clonidine do not appear to interact with the same receptor site, the observed functional antagonism suggests the release of an endogenous opiate by clonidine or alpha-methyldopa and the possible role of the opiate in the central control of sympathetic tone.", "contents": "Naloxone reverses the antihypertensive effect of clonidine. In unanesthetized, spontaneously hypertensive rats the decrease in blood pressure and heart rate produced by intravenous clonidine, 5 to 20 micrograms/kg, was inhibited or reversed by nalozone, 0.2 to 2 mg/kg. The hypotensive effect of 100 mg/kg alpha-methyldopa was also partially reversed by naloxone. Naloxone alone did not affect either blood pressure or heart rate. In brain membranes from spontaneously hypertensive rats clonidine, 10(-8) to 10(-5) M, did not influence stereoselective binding of [3H]-naloxone (8 nM), and naloxone, 10(-8) to 10(-4) M, did not influence clonidine-suppressible binding of [3H]-dihydroergocryptine (1 nM). These findings indicate that in spontaneously hypertensive rats the effects of central alpha-adrenoceptor stimulation involve activation of opiate receptors. As naloxone and clonidine do not appear to interact with the same receptor site, the observed functional antagonism suggests the release of an endogenous opiate by clonidine or alpha-methyldopa and the possible role of the opiate in the central control of sympathetic tone."}
{"id": "PMID:227509", "title": "Modulation of sympathetic transmission by neuronally-released dopamine.", "content": "1 When rabbits were pretreated with Fla-63, there was a marked inhibition of dopamine-beta-hydroxylase such that, after incubation of the ear arteries with [3H]-dopamine 47.2% of the tritium in the tissue was retained as unchanged dopamine. 2 [3H]-dopamine was released by stimulation of the sympathetic nerves in ear arteries taken from rabbits pretreated with Fla-63 and incubated with [3H]-dopamine. 3 The dopamine antagonists metoclopramide (1.0 microM) and ergometrine (1.0 microM) enhanced the stimulation-induced efflux of tritium in ear arteries taken from rabbits pretreated with Fla-63 and incubated with [3H]-dopamine, but not when the arteries were incubated with [3H]-noradrenaline. 4. These results suggest that if dopamine is present in the transmitter stores, it can be released by stimulation of the sympathetic nerves, and if the amount is adequate, it can activate an inhibitory feedback loop where prejunctional dopamine receptors are present.", "contents": "Modulation of sympathetic transmission by neuronally-released dopamine. 1 When rabbits were pretreated with Fla-63, there was a marked inhibition of dopamine-beta-hydroxylase such that, after incubation of the ear arteries with [3H]-dopamine 47.2% of the tritium in the tissue was retained as unchanged dopamine. 2 [3H]-dopamine was released by stimulation of the sympathetic nerves in ear arteries taken from rabbits pretreated with Fla-63 and incubated with [3H]-dopamine. 3 The dopamine antagonists metoclopramide (1.0 microM) and ergometrine (1.0 microM) enhanced the stimulation-induced efflux of tritium in ear arteries taken from rabbits pretreated with Fla-63 and incubated with [3H]-dopamine, but not when the arteries were incubated with [3H]-noradrenaline. 4. These results suggest that if dopamine is present in the transmitter stores, it can be released by stimulation of the sympathetic nerves, and if the amount is adequate, it can activate an inhibitory feedback loop where prejunctional dopamine receptors are present."}
{"id": "PMID:227510", "title": "Effects of the venom of the green mamba, Dendroaspis angusticeps on skeletal muscle and neuromuscular transmission.", "content": "1 The venom of the green mamba, Dendroaspis angusticeps, was tested for effects on neuromuscular transmission and skeletal muscle contractility in isolated phrenic nerve-hemidiaphragm preparations of the rat and mouse, chick biventer cervicis muscle preparations and in aneural cultures of embryonic chick skeletal muscle. 2 The venom (10 to 40 micrograms/ml) augmented the responses to indirect but not direct stimulation. As the venom did not have anticholinesterase activity and did not increase receptor sensitivity, it is likely that the venom enhanced release of acetylcholine. 3 Higher concentrations of venom (40 to 80 micrograms/ml) inhibited acetylcholine receptor sensitivity. 4 Prolonged exposure to the higher concentrations of venom produced a failure of muscle contractility. Signs of muscle degeneration were seen in skeletal muscle cultures.", "contents": "Effects of the venom of the green mamba, Dendroaspis angusticeps on skeletal muscle and neuromuscular transmission. 1 The venom of the green mamba, Dendroaspis angusticeps, was tested for effects on neuromuscular transmission and skeletal muscle contractility in isolated phrenic nerve-hemidiaphragm preparations of the rat and mouse, chick biventer cervicis muscle preparations and in aneural cultures of embryonic chick skeletal muscle. 2 The venom (10 to 40 micrograms/ml) augmented the responses to indirect but not direct stimulation. As the venom did not have anticholinesterase activity and did not increase receptor sensitivity, it is likely that the venom enhanced release of acetylcholine. 3 Higher concentrations of venom (40 to 80 micrograms/ml) inhibited acetylcholine receptor sensitivity. 4 Prolonged exposure to the higher concentrations of venom produced a failure of muscle contractility. Signs of muscle degeneration were seen in skeletal muscle cultures."}
{"id": "PMID:227511", "title": "The failure of indomethacin to alter ACTH-induced adrenal hyperaemia or steroidogenesis in the anaesthetized dog.", "content": "1 The response of adrenal blood flow to adrenocorticotropic hormone (ACTH) was measured with radioactive microspheres in anaesthetized, dexamethasone-treated, mongrel dog. 2 Adrenocorticotropic hormone (2 u/h i.v.) increased adrenal blood flow within 15 min and this persisted for the duration of the infusion. 3 Cortisol concentrations also rose with ACTH infusion. 4 Indomethacin (6 mg/kg i.v. followed by 1 mg/min) did not effect the adrenal response to ACTH although plasma concentrations of indomethacin (21.9 +/- 2.5 micrograms/ml) adequate to suppress prostaglandin synthesis were achieved. 5 We conclude that prostaglandins are not required for steroidogenesis or the adrenal haemodynamic response to ACTH.", "contents": "The failure of indomethacin to alter ACTH-induced adrenal hyperaemia or steroidogenesis in the anaesthetized dog. 1 The response of adrenal blood flow to adrenocorticotropic hormone (ACTH) was measured with radioactive microspheres in anaesthetized, dexamethasone-treated, mongrel dog. 2 Adrenocorticotropic hormone (2 u/h i.v.) increased adrenal blood flow within 15 min and this persisted for the duration of the infusion. 3 Cortisol concentrations also rose with ACTH infusion. 4 Indomethacin (6 mg/kg i.v. followed by 1 mg/min) did not effect the adrenal response to ACTH although plasma concentrations of indomethacin (21.9 +/- 2.5 micrograms/ml) adequate to suppress prostaglandin synthesis were achieved. 5 We conclude that prostaglandins are not required for steroidogenesis or the adrenal haemodynamic response to ACTH."}
{"id": "PMID:227512", "title": "The effects of inert gases and other general anaesthetics on the release of acetylcholine from the guinea-pig ileum.", "content": "1 The actions of a range of general anaesthetic agents on the rates of release of acetylcholine from the guinea-pig ileum were tested, by means of a superfusion system designed to maintain the tissues under physiological conditions in a high pressure chamber.2 Anaesthetic pressures of nitrous oxide, nitrogen, argon, sulphur hexafluoride and carbon tetrafluoride caused increases in acetylcholine ouput but the concentrations required did not parallel their general anaesthetic potencies. The changes were not altered by the application of a pressure of helium which reverses their general anaesthetic actions in vivo.3 Urethane (50.5 mM and 101 mM, but not 16.8 mM) decreased acetylcholine release rates and this effect was not reversed by helium pressure.4 Octanol (1.0 mM, but not 0.124 mM or 0.496 mM) decreased the acetylcholine output. This action was not reversed by helium pressure. The lack of effect on acetylcholine release from tetrodotoxin-treated tissues suggested that the changes were produced by blockade of action potential conduction.5 Phenobarbitone (0.4 mM but not 0.2 mM) also decreased acetylcholine output. Although the concentrations required were lower than those which have been previously shown to block axonal conduction, no changes were seen in tetrodotoxin-treated tissues. The decreases were less when helium pressure was applied than at atmospheric pressure but full pressure reversal, as occurs in vivo, was not seen.6 The effects on acetylcholine output exerted by the anaesthetics studied did not reflect their general anaesthetic action in the concentrations required, the direction of the changes produced or in the response to helium pressure. They represent specific actions which are likely to contribute to the individual differences which are seen between the physiological actions of the anaesthetics in vivo.", "contents": "The effects of inert gases and other general anaesthetics on the release of acetylcholine from the guinea-pig ileum. 1 The actions of a range of general anaesthetic agents on the rates of release of acetylcholine from the guinea-pig ileum were tested, by means of a superfusion system designed to maintain the tissues under physiological conditions in a high pressure chamber.2 Anaesthetic pressures of nitrous oxide, nitrogen, argon, sulphur hexafluoride and carbon tetrafluoride caused increases in acetylcholine ouput but the concentrations required did not parallel their general anaesthetic potencies. The changes were not altered by the application of a pressure of helium which reverses their general anaesthetic actions in vivo.3 Urethane (50.5 mM and 101 mM, but not 16.8 mM) decreased acetylcholine release rates and this effect was not reversed by helium pressure.4 Octanol (1.0 mM, but not 0.124 mM or 0.496 mM) decreased the acetylcholine output. This action was not reversed by helium pressure. The lack of effect on acetylcholine release from tetrodotoxin-treated tissues suggested that the changes were produced by blockade of action potential conduction.5 Phenobarbitone (0.4 mM but not 0.2 mM) also decreased acetylcholine output. Although the concentrations required were lower than those which have been previously shown to block axonal conduction, no changes were seen in tetrodotoxin-treated tissues. The decreases were less when helium pressure was applied than at atmospheric pressure but full pressure reversal, as occurs in vivo, was not seen.6 The effects on acetylcholine output exerted by the anaesthetics studied did not reflect their general anaesthetic action in the concentrations required, the direction of the changes produced or in the response to helium pressure. They represent specific actions which are likely to contribute to the individual differences which are seen between the physiological actions of the anaesthetics in vivo."}
{"id": "PMID:227513", "title": "The subdivision of beta-adrenoceptors in the cardiovascular system of the rat.", "content": "1 The antagonism by the beta-adrenoceptor blocking drugs, propranolol (non-selective) and practolol (beta-selective), of the cardiovascular actions of isoprenaline has been investigated in the rat. 2 All doses of practolol (0.1, 1 and 3 mg/kg) blocked the cardio-accelerator action of isoprenaline but only the largest dose blocked the vasodilator effect. 3 All doses of propranolol (0.01, 0.03 and 0.1 mg/kg) blocked the vasodilator effect of isoprenaline but only the largest dose diminished the tachycardia. 4 It is concluded that in the rat, as in other species, beta-adrenoceptors may be subdivided into beta 1 (cardiac) and beta 2 (peripheral vascular) types.", "contents": "The subdivision of beta-adrenoceptors in the cardiovascular system of the rat. 1 The antagonism by the beta-adrenoceptor blocking drugs, propranolol (non-selective) and practolol (beta-selective), of the cardiovascular actions of isoprenaline has been investigated in the rat. 2 All doses of practolol (0.1, 1 and 3 mg/kg) blocked the cardio-accelerator action of isoprenaline but only the largest dose blocked the vasodilator effect. 3 All doses of propranolol (0.01, 0.03 and 0.1 mg/kg) blocked the vasodilator effect of isoprenaline but only the largest dose diminished the tachycardia. 4 It is concluded that in the rat, as in other species, beta-adrenoceptors may be subdivided into beta 1 (cardiac) and beta 2 (peripheral vascular) types."}
{"id": "PMID:227525", "title": "Nephroblastoma: treatment during 1970-3 and the effect on survival of inclusion in the first MRC trial.", "content": "In 1970-3 313 children were diagnosed as having nephroblastoma in Great Britain. From the start of the first Medical Research Council nephroblastoma study in October 1970 until the end of 1973, 98 children (57% of all eligible children) were included in the trial. Of the 313 children, 288 (92%) had a nephrectomy, 248 (79%) received a course of radiotherapy, and 267 (85%) were given at least four days' chemotherapy. The three-year survival rate was 58%; the rate among children in the trial (77%) was significantly better than that among children who were eligible for the trial but not included (58%). Children who had nephrectomies at specialised children's and teaching hospitals had a higher survival rate than those treated elsewhere. All children with nephroblastoma should be treated according to well-defined protocols which take into account the age of the child and the stage of the tumour and include a full course of maintenance chemotherapy.", "contents": "Nephroblastoma: treatment during 1970-3 and the effect on survival of inclusion in the first MRC trial. In 1970-3 313 children were diagnosed as having nephroblastoma in Great Britain. From the start of the first Medical Research Council nephroblastoma study in October 1970 until the end of 1973, 98 children (57% of all eligible children) were included in the trial. Of the 313 children, 288 (92%) had a nephrectomy, 248 (79%) received a course of radiotherapy, and 267 (85%) were given at least four days' chemotherapy. The three-year survival rate was 58%; the rate among children in the trial (77%) was significantly better than that among children who were eligible for the trial but not included (58%). Children who had nephrectomies at specialised children's and teaching hospitals had a higher survival rate than those treated elsewhere. All children with nephroblastoma should be treated according to well-defined protocols which take into account the age of the child and the stage of the tumour and include a full course of maintenance chemotherapy."}
{"id": "PMID:227527", "title": "Tegmentoreticular projections with special reference to the muscular atonia during paradoxical sleep in the cat: an HRP study.", "content": "Using the retrograde tracer technique with horseradish peroxidase (HRP), attempts were made to determine the cells of origin and the descending pathway of the tegmentoreticular projections in order to give an anatomical substrate for the physiological phenomenon of the postural atonia observed during paradoxical sleep (PS) in the cat. The HRP was injected into various parts of the pontomedullary reticular formation (RF) including the caudal raphe nuclei, nucleus (n.) reticularis gigantocellularis (Gc), n. reticularis magnocellularis (Mc), and other pontomedullary structures adjacent to the Mc. The results indicated that the HRP injection into the Mc, particularly its caudal and lateral two-thirds, resulted in specific labeling of cells located in an area just medial to the LCa together with those in the most medial part of the LCa. Bilateral lesions of these pontine structures have been reported to suppress the atonia otherwise observed during PS in the normal cat. In addition to the HRP labeled cells, we have also observed HRP filled fiber bundles directed to labeled cells in the medial part of the LCa and immediately adjacent tegmental RF area. The same course of HRP labeled fiber bundles was also observed together with HRP labeled cells in the Mc after HRP injections into the medial part of the LCa area, indicating the existence of an interconnection between the LCa area and the Mc. The location of the tegmentoreticular pathway corresponded to that of the lesions effective to suppress the muscular atonia during PS. HRP injections into the caudal medullar caudal to the Mc, on the other hand, resulted in no or almost no HRP labeled cells in the area medial to the LCa, in spite of the presence of HRP containing neurons in other parts of the pontomedullary RF areas, showing that the tegmentoreticular projections as described above terminate almost exclusively in the Mc.", "contents": "Tegmentoreticular projections with special reference to the muscular atonia during paradoxical sleep in the cat: an HRP study. Using the retrograde tracer technique with horseradish peroxidase (HRP), attempts were made to determine the cells of origin and the descending pathway of the tegmentoreticular projections in order to give an anatomical substrate for the physiological phenomenon of the postural atonia observed during paradoxical sleep (PS) in the cat. The HRP was injected into various parts of the pontomedullary reticular formation (RF) including the caudal raphe nuclei, nucleus (n.) reticularis gigantocellularis (Gc), n. reticularis magnocellularis (Mc), and other pontomedullary structures adjacent to the Mc. The results indicated that the HRP injection into the Mc, particularly its caudal and lateral two-thirds, resulted in specific labeling of cells located in an area just medial to the LCa together with those in the most medial part of the LCa. Bilateral lesions of these pontine structures have been reported to suppress the atonia otherwise observed during PS in the normal cat. In addition to the HRP labeled cells, we have also observed HRP filled fiber bundles directed to labeled cells in the medial part of the LCa and immediately adjacent tegmental RF area. The same course of HRP labeled fiber bundles was also observed together with HRP labeled cells in the Mc after HRP injections into the medial part of the LCa area, indicating the existence of an interconnection between the LCa area and the Mc. The location of the tegmentoreticular pathway corresponded to that of the lesions effective to suppress the muscular atonia during PS. HRP injections into the caudal medullar caudal to the Mc, on the other hand, resulted in no or almost no HRP labeled cells in the area medial to the LCa, in spite of the presence of HRP containing neurons in other parts of the pontomedullary RF areas, showing that the tegmentoreticular projections as described above terminate almost exclusively in the Mc."}
{"id": "PMID:227528", "title": "The depressive effects of morphine on the C fibre response of dorsal horn neurones in the spinal rat pretreated or not by pCPA.", "content": "(1) The effects of morphine upon the transmission of nociceptive messages at the spinal level have been investigated in the spinal rat. The responses of dorsal horn cells induced by the activation of C fibres were depressed in all cases in a dose-dependent fashion, this effect being reversed by the opiate antagonist naloxone. An estimation of the ED50 at the cellular level leads to the value of 6.3 mg/kg. The responses to A delta fibres were also depressed dose-dependently whereas the responses to A alpha fibres were unaffected. This is a confirmation in the rat of the differential effects of morphine on responses of convergent units elicited by the stimulation of different fibres, as previously described in the cat. (2) The hypothesis of the participation of serotonergic terminals in these effects has been checked by comparing the preceding results to those obtained in pCPA pretreated animals. Two populations of units were observed in the latter group: two-thirds of cells showed a dose-response curve similar to that of the non-pretreated group whereas the remaining one-third were unaffected either by morphine or naloxone. It is concluded that, at least, two mechanisms are involved in the depressive effects of morphine at the spinal level, serotonergic terminals being implicated in one of these. (3) The lowering of spinal cord serotonin content was associated with a decrease of both the size of the excitatory receptive field (34%) and the activities related to C fibre input (36%) of the recorded dorsal horn cells. This result is discussed with reference to the excitatory or sensitizatory effect of serotonin upon chemoreceptors related to pain.", "contents": "The depressive effects of morphine on the C fibre response of dorsal horn neurones in the spinal rat pretreated or not by pCPA. (1) The effects of morphine upon the transmission of nociceptive messages at the spinal level have been investigated in the spinal rat. The responses of dorsal horn cells induced by the activation of C fibres were depressed in all cases in a dose-dependent fashion, this effect being reversed by the opiate antagonist naloxone. An estimation of the ED50 at the cellular level leads to the value of 6.3 mg/kg. The responses to A delta fibres were also depressed dose-dependently whereas the responses to A alpha fibres were unaffected. This is a confirmation in the rat of the differential effects of morphine on responses of convergent units elicited by the stimulation of different fibres, as previously described in the cat. (2) The hypothesis of the participation of serotonergic terminals in these effects has been checked by comparing the preceding results to those obtained in pCPA pretreated animals. Two populations of units were observed in the latter group: two-thirds of cells showed a dose-response curve similar to that of the non-pretreated group whereas the remaining one-third were unaffected either by morphine or naloxone. It is concluded that, at least, two mechanisms are involved in the depressive effects of morphine at the spinal level, serotonergic terminals being implicated in one of these. (3) The lowering of spinal cord serotonin content was associated with a decrease of both the size of the excitatory receptive field (34%) and the activities related to C fibre input (36%) of the recorded dorsal horn cells. This result is discussed with reference to the excitatory or sensitizatory effect of serotonin upon chemoreceptors related to pain."}
{"id": "PMID:227529", "title": "The influence of naloxone on the C fiber response of dorsal horn neurons and their inhibitory control by raphe magnus stimulation.", "content": "In intact rats anesthetized with chloralose, the effects of naloxone were studied on the responses of spinal cord dorsal horn neurons to C fiber stimulation and upon the inhibition induced on these responses by stimulation of the nucleus raph\u00e9 magnus (NRM). (1) A mean 44% facilitatory effect on responses to C fibers was observed for 12/19 units. (2) A mean 30% reduction of the inhibitory effects of NRM was found for 14/29 units. (3) However there is no clear relationship between these facilitatory effects and the diminution of the efficiency of NRM stimulation. These results demonstrate a facilitatory effect of naloxone upon the transmission of noxious messages at the spinal level and confirm that opiate endogenous substances are implicated in the inhibitory mechanisms activated by stimulation of NRM.", "contents": "The influence of naloxone on the C fiber response of dorsal horn neurons and their inhibitory control by raphe magnus stimulation. In intact rats anesthetized with chloralose, the effects of naloxone were studied on the responses of spinal cord dorsal horn neurons to C fiber stimulation and upon the inhibition induced on these responses by stimulation of the nucleus raph\u00e9 magnus (NRM). (1) A mean 44% facilitatory effect on responses to C fibers was observed for 12/19 units. (2) A mean 30% reduction of the inhibitory effects of NRM was found for 14/29 units. (3) However there is no clear relationship between these facilitatory effects and the diminution of the efficiency of NRM stimulation. These results demonstrate a facilitatory effect of naloxone upon the transmission of noxious messages at the spinal level and confirm that opiate endogenous substances are implicated in the inhibitory mechanisms activated by stimulation of NRM."}
{"id": "PMID:227532", "title": "The localization of receptor binding sites in the substantia nigra and striatum of the rat.", "content": "Neurotransmitter receptor binding of 5 ligands was examined in the striatum, substantia nigra (SN) and frontal cortex of rats which had received either unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal pathway (NSP) or unilateral kainic acid lesions of the striatum. 6-OHDA lesions of the NSP significantly reduced [3H]dihydroalprenolol ([3H]DHA) and [3H]naloxone ([3H]Nal) binding by 31% and 28% respectively, in the denervated striatum compared to the contralateral side. Scatchard analysis revealed that the alteration in [3H]DHA binding was not due to a change in the affinity of the beta-adrenergic receptor for [3H]DHA. In marked contrast to these changes in the striatum, destruction of the NSP resulted in a significant increase in [3H]DHA and [3H]Nal binding by 44% and 26%, respectively, in the frontal cortex of the lesioned compared to the control side. 6-OHDA lesions in the NSP did not alter striatal receptor binding for [3H]quinuclidinyl benzilate ([3H]QNB), [3H]muscimol ([3H]Mus) or [3H]flunitrazepam ([3H]Flu). Similarily, intrastriatal kainic acid injections did not alter striatal receptor binding for [3H]Nal, [3H]Flu or [3H]Mus. Of the various receptor densities measured in the SN after the above lesions the only alteration observed was a 43% increase in [3H]Flu binding following 6-OHDA lesions of the NSP. Scatchard analysis indicated no change in the affinity of the benzodiazepine receptor for [3H]Flu. 6-OHDA lesions of the NSP did not alter [13H]QNB or [3H]Nal binding in the SN. Striatal kainic acid lesions did not alter nigral [3H]QNB or [3H]Flu binding. The results are discussed in terms of neurotransmitter localization and plasticity within the striatum, SN and frontal cortex.", "contents": "The localization of receptor binding sites in the substantia nigra and striatum of the rat. Neurotransmitter receptor binding of 5 ligands was examined in the striatum, substantia nigra (SN) and frontal cortex of rats which had received either unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal pathway (NSP) or unilateral kainic acid lesions of the striatum. 6-OHDA lesions of the NSP significantly reduced [3H]dihydroalprenolol ([3H]DHA) and [3H]naloxone ([3H]Nal) binding by 31% and 28% respectively, in the denervated striatum compared to the contralateral side. Scatchard analysis revealed that the alteration in [3H]DHA binding was not due to a change in the affinity of the beta-adrenergic receptor for [3H]DHA. In marked contrast to these changes in the striatum, destruction of the NSP resulted in a significant increase in [3H]DHA and [3H]Nal binding by 44% and 26%, respectively, in the frontal cortex of the lesioned compared to the control side. 6-OHDA lesions in the NSP did not alter striatal receptor binding for [3H]quinuclidinyl benzilate ([3H]QNB), [3H]muscimol ([3H]Mus) or [3H]flunitrazepam ([3H]Flu). Similarily, intrastriatal kainic acid injections did not alter striatal receptor binding for [3H]Nal, [3H]Flu or [3H]Mus. Of the various receptor densities measured in the SN after the above lesions the only alteration observed was a 43% increase in [3H]Flu binding following 6-OHDA lesions of the NSP. Scatchard analysis indicated no change in the affinity of the benzodiazepine receptor for [3H]Flu. 6-OHDA lesions of the NSP did not alter [13H]QNB or [3H]Nal binding in the SN. Striatal kainic acid lesions did not alter nigral [3H]QNB or [3H]Flu binding. The results are discussed in terms of neurotransmitter localization and plasticity within the striatum, SN and frontal cortex."}
{"id": "PMID:227533", "title": "Biochemical and immunohistochemical studies on dysmyelination of quaking mutant mice in vivo and in vitro.", "content": "Dysmyelination in the central nervous system of the quaking mutant mouse was studied biochemically and immunohistochemically. We found, by measuring CNPase activity, that myelination in the central nervous system of quaking mice was affected to a different degree in different areas. The pallium cerebri was the most severely affected and the medulla and spinal cord were least affected. The density of astroglia observed by GFA staining wash higher in the white matter of quaking mice than in controls, but the total area of the white matter in the cerebellum was smaller in the quaking mice than in the controls. The DNA content in the pallium cerebri and brain stem showed no increase and that of the cerebellum was even lower in quaking mice than in the controls. Hypertrophy of the astroglia was observed in the white matter of the cerebellum of quaking mice, though Bergmann astroglial fibers in the molecular layer did not show any hypertrophy. The cerebella of quaking mice in primary culture showed very poor myelination under the phase-contrast microscope. However, Purkinje cells from the quaking mutants appeared normal with regard to Bodian silver impregnation, hematoxylineosin staining, and Purkinje cell specific P 400 protein. Addition of the conditioned culture medium of qk/qk to the culture of the control cerebellum did not interfere with the myelination. We concluded that the cause of dysmyelination in the quaking mouse could be a genetic defect of the oligodendroglia rather than hypertrophy of the astroglial cells.", "contents": "Biochemical and immunohistochemical studies on dysmyelination of quaking mutant mice in vivo and in vitro. Dysmyelination in the central nervous system of the quaking mutant mouse was studied biochemically and immunohistochemically. We found, by measuring CNPase activity, that myelination in the central nervous system of quaking mice was affected to a different degree in different areas. The pallium cerebri was the most severely affected and the medulla and spinal cord were least affected. The density of astroglia observed by GFA staining wash higher in the white matter of quaking mice than in controls, but the total area of the white matter in the cerebellum was smaller in the quaking mice than in the controls. The DNA content in the pallium cerebri and brain stem showed no increase and that of the cerebellum was even lower in quaking mice than in the controls. Hypertrophy of the astroglia was observed in the white matter of the cerebellum of quaking mice, though Bergmann astroglial fibers in the molecular layer did not show any hypertrophy. The cerebella of quaking mice in primary culture showed very poor myelination under the phase-contrast microscope. However, Purkinje cells from the quaking mutants appeared normal with regard to Bodian silver impregnation, hematoxylineosin staining, and Purkinje cell specific P 400 protein. Addition of the conditioned culture medium of qk/qk to the culture of the control cerebellum did not interfere with the myelination. We concluded that the cause of dysmyelination in the quaking mouse could be a genetic defect of the oligodendroglia rather than hypertrophy of the astroglial cells."}
{"id": "PMID:227534", "title": "Biochemical characterization of postsynaptically localized cyclic nucleotide phosphodiesterase.", "content": "This study demonstrates the postsynaptic localization of one of the isozymes of cyclic nucleotide phosphodiesterase (PDE) activity at asymmetrical, axospinous terminals in the rat corpus striatum and neocortex. Characterization of this enzymatic activity demonstrates that the PDE form surviving aldehyde fixation for electron cytochemistry can be considered to preferentially hydrolyze cyclic 3'5'-guanosine monophosphate, and it requires calcium and a heat-stable calcium-dependent regulator protein (CDR) for full hydrolytic activity. Ion exchange chromatographic analysis of extracts of corresponding unfixed brain regions demonstrates that only one enzyme activity peak exhibits similar aldehyde resistance and calcium and regulator protein activatibility.", "contents": "Biochemical characterization of postsynaptically localized cyclic nucleotide phosphodiesterase. This study demonstrates the postsynaptic localization of one of the isozymes of cyclic nucleotide phosphodiesterase (PDE) activity at asymmetrical, axospinous terminals in the rat corpus striatum and neocortex. Characterization of this enzymatic activity demonstrates that the PDE form surviving aldehyde fixation for electron cytochemistry can be considered to preferentially hydrolyze cyclic 3'5'-guanosine monophosphate, and it requires calcium and a heat-stable calcium-dependent regulator protein (CDR) for full hydrolytic activity. Ion exchange chromatographic analysis of extracts of corresponding unfixed brain regions demonstrates that only one enzyme activity peak exhibits similar aldehyde resistance and calcium and regulator protein activatibility."}
{"id": "PMID:227541", "title": "Cation transport and membrane potential properties of primary astroglial cultures from neonatal rat brains.", "content": "This paper describes K+ and Na+ content and transport in primary monolayer cultures from dissociated newborn rat brains, considered to consist predominantly of astroglial cells. Net changes in cation content after addition of ouabain, and steady state fluxes using 86Rb+ as a marker for K+ and 22Na+ as a marker for Na+, were measured. The results found indicate that the cells maintained a conventional pattern of cation homeostasis with net efflux of K+ being balanced by its active uptake and net uptake of Na+ balanced by active extrusion mediated by a ouabain sensitive (Na+K) pump. These processes maintained internal measured K+:Na+ ratios of 12--25:1. The cells were normally flat but addition of DBcAMP caused them to round up and form numerous processes, an appearance resembling that of astroglial cells in vivo. DBcAMP treatment also reduced the steady state levels of K+ measured with 86Rb+ by 15--30%, and had no effect on initial rates of 86Rb+ and 22Na+ uptake. The membrane potentials of cells treated with DBcAMP were studied, since only these were easily impaled. The membrane potentials of separate groups of cells gave means ranging from --65 to --75 mV at 35 degrees C, at an external K+ concentration ([K+]o) of 4.5 mM. The dependence of the membrane potentials of individual cells and groups of cells on [K+]o was studied. The slope of the potential per 10-fold change in [K+]o was 55--57 mV, at concentrations of K+ greater than 10--20 mM K+, and diverged from this slope at concentrations below this. This shows that these cells had some permeability to ions other than K+. Assuming that Na+ was the only other ion affecting the membrane potential, it was calculated that the permeability to Na+ was about 30 times less than K+. A similar result was obtained based on estimates of Na+ and K+ permeability from transport experiments on cells also treated with DBcAMP. The results obtained from these cells are compared to those found for other cultured glial cells and glial cells in vivo. We conclude that the membrane potentials of the cultured cells used in the present study show the closest resemblance so far to glia in vivo, since they are large and negative and are determined mainly by K+. However, the cultured cells have different properties from those reported in some studies for glial cells in vivo by showing free permeability to ions other than K+.", "contents": "Cation transport and membrane potential properties of primary astroglial cultures from neonatal rat brains. This paper describes K+ and Na+ content and transport in primary monolayer cultures from dissociated newborn rat brains, considered to consist predominantly of astroglial cells. Net changes in cation content after addition of ouabain, and steady state fluxes using 86Rb+ as a marker for K+ and 22Na+ as a marker for Na+, were measured. The results found indicate that the cells maintained a conventional pattern of cation homeostasis with net efflux of K+ being balanced by its active uptake and net uptake of Na+ balanced by active extrusion mediated by a ouabain sensitive (Na+K) pump. These processes maintained internal measured K+:Na+ ratios of 12--25:1. The cells were normally flat but addition of DBcAMP caused them to round up and form numerous processes, an appearance resembling that of astroglial cells in vivo. DBcAMP treatment also reduced the steady state levels of K+ measured with 86Rb+ by 15--30%, and had no effect on initial rates of 86Rb+ and 22Na+ uptake. The membrane potentials of cells treated with DBcAMP were studied, since only these were easily impaled. The membrane potentials of separate groups of cells gave means ranging from --65 to --75 mV at 35 degrees C, at an external K+ concentration ([K+]o) of 4.5 mM. The dependence of the membrane potentials of individual cells and groups of cells on [K+]o was studied. The slope of the potential per 10-fold change in [K+]o was 55--57 mV, at concentrations of K+ greater than 10--20 mM K+, and diverged from this slope at concentrations below this. This shows that these cells had some permeability to ions other than K+. Assuming that Na+ was the only other ion affecting the membrane potential, it was calculated that the permeability to Na+ was about 30 times less than K+. A similar result was obtained based on estimates of Na+ and K+ permeability from transport experiments on cells also treated with DBcAMP. The results obtained from these cells are compared to those found for other cultured glial cells and glial cells in vivo. We conclude that the membrane potentials of the cultured cells used in the present study show the closest resemblance so far to glia in vivo, since they are large and negative and are determined mainly by K+. However, the cultured cells have different properties from those reported in some studies for glial cells in vivo by showing free permeability to ions other than K+."}
{"id": "PMID:227547", "title": "[Adaptation of blood sugar regulation during individually adjusted muscular exercises. Effects of training].", "content": "A twenty minutes exercise at 50 to 70% of VO2 max is followed by an increase of glycemia and F.F.A. Moderate physical activities could improve a better use of F.F.A., perhaps preferably to the glucose. Cortisol and A.C.T.H. levels raise, principally by the untrained subjects; however, that exercise is followed by a raise of STH, no dependent to the training's degree.", "contents": "[Adaptation of blood sugar regulation during individually adjusted muscular exercises. Effects of training]. A twenty minutes exercise at 50 to 70% of VO2 max is followed by an increase of glycemia and F.F.A. Moderate physical activities could improve a better use of F.F.A., perhaps preferably to the glucose. Cortisol and A.C.T.H. levels raise, principally by the untrained subjects; however, that exercise is followed by a raise of STH, no dependent to the training's degree."}
{"id": "PMID:227548", "title": "[Arterial blood pressure and high calcium diet in normal and mineralcorticoid (DOCA and sodium chloride hypertensive rats].", "content": "High calcium diet induces an hypertension lasting one week in normal rats. In mineralocorticoid treated rats (DOCA + NaCl), the same diet prevents for 10 weeks the increase of arterial blood pressure. Parathyroid activity (estimated by urinary cAMP) is decreased after the high calcium diet. These results confirm the role of the parathyroid glands in mineralocorticoid hypertension in the rat.", "contents": "[Arterial blood pressure and high calcium diet in normal and mineralcorticoid (DOCA and sodium chloride hypertensive rats]. High calcium diet induces an hypertension lasting one week in normal rats. In mineralocorticoid treated rats (DOCA + NaCl), the same diet prevents for 10 weeks the increase of arterial blood pressure. Parathyroid activity (estimated by urinary cAMP) is decreased after the high calcium diet. These results confirm the role of the parathyroid glands in mineralocorticoid hypertension in the rat."}
{"id": "PMID:227550", "title": "Pseudorabies: adaptation of the countercurrent immunoelectrophoresis for the detection of antibodies in porcine serum.", "content": "A countercurrent immunoelectrophoresis test was developed for the detection of precipitating antibodies to pseudorabies virus in pig serum. The precipitation reaction occurred only between the pseudorables antigen and the homologous porcine antiserum. The sensitivity of the method was compared to that of the serum neutralization test. On the basis of its sensitivity, its specificity and the rapidity with which the results were obtained, the countercurrent immunoelectrophoresis may become a potentially valuable screening method to test large numbers of porcine serum.", "contents": "Pseudorabies: adaptation of the countercurrent immunoelectrophoresis for the detection of antibodies in porcine serum. A countercurrent immunoelectrophoresis test was developed for the detection of precipitating antibodies to pseudorabies virus in pig serum. The precipitation reaction occurred only between the pseudorables antigen and the homologous porcine antiserum. The sensitivity of the method was compared to that of the serum neutralization test. On the basis of its sensitivity, its specificity and the rapidity with which the results were obtained, the countercurrent immunoelectrophoresis may become a potentially valuable screening method to test large numbers of porcine serum."}
{"id": "PMID:227551", "title": "Effect of temperature, relative humidity and medium on the aerosol stability of infectious bovine rhinotracheitis virus.", "content": "Aerosols of infectious bovine rhinotracheitis virus were generated with a Devilbiss 40 nebulizer from Eagle's minimum essential medium, nasal secretion from a noninfected calf and nasal secretion from a calf artificially infected with infectious bovine rhinotracheitis virus and aged in a rotating drum at temperatures of 6 degrees C or 32 degrees C and relative humidities of 30% or 90%. The aerosols were sampled at seven minutes after start of spraying, one hour, two hours and three hours with an all glass impinger (AGI-30) and titrated for infectivity in cell cultures. Physical decay was determined by a rhodamine B tracer technique. During spraying (seven minutes from start of spraying), the virus was usually more stable in aerosols of nasal secretion from a noninfected calf and at 90% relative humidity. In nasal secretion from a noninfected calf the virus survived best at 90% relative humidity when the temperature was 6 degrees C and best at 30% relative humidity when the temperature was 32 degrees C. During aging, biological decay was greater at the higher temperature, and at 6 degrees C, the highest decay rates occurred at 30% relative humidity in Eagle's minimum essential medium and at 90% relative humidity in nasal secretion from a noninfected calf. The stability of infectious bovine rhinotracheitis virus infected nasal secretion was not widely different from that in noninfected nasal secretion, although under certain conditions greater survival occurred in the noninfected secretion.", "contents": "Effect of temperature, relative humidity and medium on the aerosol stability of infectious bovine rhinotracheitis virus. Aerosols of infectious bovine rhinotracheitis virus were generated with a Devilbiss 40 nebulizer from Eagle's minimum essential medium, nasal secretion from a noninfected calf and nasal secretion from a calf artificially infected with infectious bovine rhinotracheitis virus and aged in a rotating drum at temperatures of 6 degrees C or 32 degrees C and relative humidities of 30% or 90%. The aerosols were sampled at seven minutes after start of spraying, one hour, two hours and three hours with an all glass impinger (AGI-30) and titrated for infectivity in cell cultures. Physical decay was determined by a rhodamine B tracer technique. During spraying (seven minutes from start of spraying), the virus was usually more stable in aerosols of nasal secretion from a noninfected calf and at 90% relative humidity. In nasal secretion from a noninfected calf the virus survived best at 90% relative humidity when the temperature was 6 degrees C and best at 30% relative humidity when the temperature was 32 degrees C. During aging, biological decay was greater at the higher temperature, and at 6 degrees C, the highest decay rates occurred at 30% relative humidity in Eagle's minimum essential medium and at 90% relative humidity in nasal secretion from a noninfected calf. The stability of infectious bovine rhinotracheitis virus infected nasal secretion was not widely different from that in noninfected nasal secretion, although under certain conditions greater survival occurred in the noninfected secretion."}
{"id": "PMID:227552", "title": "Antibodies to bovine leukemia virus in a leukosis dairy herd and suggestions for control of the infection.", "content": "A closed herd of 765 Holstein-Friesian dairy cattle with a history of multiple cases of leukosis was tested for antibodies to bovine leukemia virus by the bovine leukemia-glycoprotein immunodiffusion test. A total of 355 animals (46.4%) were antibody positive. Prevalence was 60% in the 373 milking cows and 100% in the breeding bulls. Antibodies were present in 59% of newborn calves. Prevalence of antibodies was higher in older animals and cows in second lactation had a higher prevalence than cows in first lactation (72% vs 43%). Proposed control measures in this herd aim at preventing infection of calves, heifers and lactating cows by: 1) separating them into groups negative and positive for bovine leukemia virus antibodies, 2) not allowing calves to receive colstrum or milk from infected cows and 3) by using seronegative bulls for natural breeding tested at three month intervals. Calves should be tested after six months of age. Before this time calves of positive mothers should be treated as being positive.", "contents": "Antibodies to bovine leukemia virus in a leukosis dairy herd and suggestions for control of the infection. A closed herd of 765 Holstein-Friesian dairy cattle with a history of multiple cases of leukosis was tested for antibodies to bovine leukemia virus by the bovine leukemia-glycoprotein immunodiffusion test. A total of 355 animals (46.4%) were antibody positive. Prevalence was 60% in the 373 milking cows and 100% in the breeding bulls. Antibodies were present in 59% of newborn calves. Prevalence of antibodies was higher in older animals and cows in second lactation had a higher prevalence than cows in first lactation (72% vs 43%). Proposed control measures in this herd aim at preventing infection of calves, heifers and lactating cows by: 1) separating them into groups negative and positive for bovine leukemia virus antibodies, 2) not allowing calves to receive colstrum or milk from infected cows and 3) by using seronegative bulls for natural breeding tested at three month intervals. Calves should be tested after six months of age. Before this time calves of positive mothers should be treated as being positive."}
{"id": "PMID:227553", "title": "A rapid plaque neutralization test for bluetongue virus.", "content": "A bluetongue virus plaque neutralization test, done in small tissue culture wells (2.0 cm2) using minimal antibody-virus contact time, was found to be of comparable sensitivity to more classical methods involving preincubation. By using the cell culture plates as serum dilution wells and adding cells directly to the virus-antibody mixture, a considerable saving in time is realized. Because of the small size of the wells, reagent cost and incubator space requirements are reduced making the test much more attractive for wide scale use, either as a screening test or one that yields dose-response lines.", "contents": "A rapid plaque neutralization test for bluetongue virus. A bluetongue virus plaque neutralization test, done in small tissue culture wells (2.0 cm2) using minimal antibody-virus contact time, was found to be of comparable sensitivity to more classical methods involving preincubation. By using the cell culture plates as serum dilution wells and adding cells directly to the virus-antibody mixture, a considerable saving in time is realized. Because of the small size of the wells, reagent cost and incubator space requirements are reduced making the test much more attractive for wide scale use, either as a screening test or one that yields dose-response lines."}
{"id": "PMID:227554", "title": "Isolation of cloned Syrian hamster insulinoma cell lines with limited capacity for insulin production.", "content": "Cell lines derived from a Syrian hamster insulinoma have been cloned in agar and maintained continuously in culture in vitro for 1 1/2 years. The cell lines have average doubling times of 48 h, they have modal chromosome numbers between 38 and 39, and they retain the ability to form tumors when injected into Syrian hamsters. The cells do not produce immunoreactive insulin when grown in vitro (less than 0.5 ng/mg protein), but do produce immunoreactive insulin when grown in vivo as tumors (mean value from six determinations = 7.1 +/- 1.5 ng/mg protein).", "contents": "Isolation of cloned Syrian hamster insulinoma cell lines with limited capacity for insulin production. Cell lines derived from a Syrian hamster insulinoma have been cloned in agar and maintained continuously in culture in vitro for 1 1/2 years. The cell lines have average doubling times of 48 h, they have modal chromosome numbers between 38 and 39, and they retain the ability to form tumors when injected into Syrian hamsters. The cells do not produce immunoreactive insulin when grown in vitro (less than 0.5 ng/mg protein), but do produce immunoreactive insulin when grown in vivo as tumors (mean value from six determinations = 7.1 +/- 1.5 ng/mg protein)."}
{"id": "PMID:227555", "title": "Investigation of a family suspected of being at high risk for cancer.", "content": "The investigation of the family of a patient with bilateral breast cancer is described. By means of interviews and the checking of hospital records and death certificates, information was obtained on 199 family members over five generations, 19 of whom had cancer. Comparison with expected numbers of cases showed an excess in only one generation. The interpretation of these findings and the advice given to family members are discussed.", "contents": "Investigation of a family suspected of being at high risk for cancer. The investigation of the family of a patient with bilateral breast cancer is described. By means of interviews and the checking of hospital records and death certificates, information was obtained on 199 family members over five generations, 19 of whom had cancer. Comparison with expected numbers of cases showed an excess in only one generation. The interpretation of these findings and the advice given to family members are discussed."}
{"id": "PMID:227556", "title": "[Isolation of infectious bovine rhinotracheitis virus from the tarsal joint of a bull (author's transl)].", "content": "Isolation of infectious bovine rhinotracheitis virus from the tarsal joint of a bullInfectious bovine rhinotracheitis virus was isolated from the right tarsal joint of a bull who was showing signs of a systemic viral infection. The clinical signs manifested by 16 bulls of this herd are described, the laboratory methods used are listed and the results are analysed and discussed.", "contents": "[Isolation of infectious bovine rhinotracheitis virus from the tarsal joint of a bull (author's transl)]. Isolation of infectious bovine rhinotracheitis virus from the tarsal joint of a bullInfectious bovine rhinotracheitis virus was isolated from the right tarsal joint of a bull who was showing signs of a systemic viral infection. The clinical signs manifested by 16 bulls of this herd are described, the laboratory methods used are listed and the results are analysed and discussed."}
{"id": "PMID:227558", "title": "The significance of concordance in mammographic interpretations.", "content": "Twenty-eight women participating in a screening program had a breast cancer diagnosed subsequent to the report of a negative mammogram which was read by only one of a group of radiologists. Fourteen occurred prior to a scheduled routine screening visit (interval cancers) and 14 were detected during such an examination. The negative mammograms from the 28 cancer patients, together with those from 120 women without cancer (controls) were independently reviewed by each member of a panel of three radiologists. Forty-six percent of the cancer cases and 5.8% of the controls were interpreted as positive by two or more of the radiologists. These findings suggest that agreement among several independent reviewers enchances the value and accuracy of mamography by reducing the number of false negative interpretations.", "contents": "The significance of concordance in mammographic interpretations. Twenty-eight women participating in a screening program had a breast cancer diagnosed subsequent to the report of a negative mammogram which was read by only one of a group of radiologists. Fourteen occurred prior to a scheduled routine screening visit (interval cancers) and 14 were detected during such an examination. The negative mammograms from the 28 cancer patients, together with those from 120 women without cancer (controls) were independently reviewed by each member of a panel of three radiologists. Forty-six percent of the cancer cases and 5.8% of the controls were interpreted as positive by two or more of the radiologists. These findings suggest that agreement among several independent reviewers enchances the value and accuracy of mamography by reducing the number of false negative interpretations."}
{"id": "PMID:227559", "title": "Nodular lymphoma with intracellular immunoglobulin.", "content": "A case of malignant lymphoma with vacuolated cells is presented and, as with two other recent reports, is of the nodular poorly differentiated lymphocytic type. This form of malignant lymphoma presumably is composed of neoplastic B lymphocytes, which produce intracellular immunoglobulins or fractions thereof, corresponding to various cellular vacuoles and inclusions. The vacuolated appearance of the neoplastic cells simulates mucinous or \"signet ring\" adenocarcinoma, which may be excluded by clinical, routine microscopic, histochemical, immunologic, and electron microscopic observations.", "contents": "Nodular lymphoma with intracellular immunoglobulin. A case of malignant lymphoma with vacuolated cells is presented and, as with two other recent reports, is of the nodular poorly differentiated lymphocytic type. This form of malignant lymphoma presumably is composed of neoplastic B lymphocytes, which produce intracellular immunoglobulins or fractions thereof, corresponding to various cellular vacuoles and inclusions. The vacuolated appearance of the neoplastic cells simulates mucinous or \"signet ring\" adenocarcinoma, which may be excluded by clinical, routine microscopic, histochemical, immunologic, and electron microscopic observations."}
{"id": "PMID:227560", "title": "Immunotherapy with levamisole: early decrease of cAMP levels in lymphocytes from treated cancer patients.", "content": "Lymphocyte cyclic nucleotide content was studied before and after Levamisole administration to cancer patients. Twelve patients with disseminated cancer received 100 mg/m2 on two consecutive days; nine comparable patients with disseminated cancer served as controls. Endogenous cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) were measured in lymphocytes before, 24, and 48 hours after ingestion of the first dose of Levamisole. A statistically significant decline in lymphocyte cAMP level was observed after drug administration and no significant changes were noted in cGMP levels. Further studies will be necessary to correlate this biochemical change in cyclic nucleotides with modulation of the functional level of cellular immune mechanisms.", "contents": "Immunotherapy with levamisole: early decrease of cAMP levels in lymphocytes from treated cancer patients. Lymphocyte cyclic nucleotide content was studied before and after Levamisole administration to cancer patients. Twelve patients with disseminated cancer received 100 mg/m2 on two consecutive days; nine comparable patients with disseminated cancer served as controls. Endogenous cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) were measured in lymphocytes before, 24, and 48 hours after ingestion of the first dose of Levamisole. A statistically significant decline in lymphocyte cAMP level was observed after drug administration and no significant changes were noted in cGMP levels. Further studies will be necessary to correlate this biochemical change in cyclic nucleotides with modulation of the functional level of cellular immune mechanisms."}
{"id": "PMID:227561", "title": "Multinucleated mammary stromal giant cells: a benign lesion that simulates invasive carcinoma.", "content": "Multinucleated stromal giant cells were found in breast tissue from 14 patients treated by mastectomy for carcinoma over 3 decades (1950s to 1970s). Nine cases were found in a review of 200 consecutive mastectomies (4.5%) performed in 1978. The average age was 51 years with nine patients in their 40s. Other than the age distribution, no association with marital status, family history of breast carcinoma, hormone usage, tumor type, or stage of disease was observed. This benign lesion of undetermined significance should not be misinterpreted as invasive carcinoma. Multinucleated stromal giant cells have been observed in breast specimens from patients not known to have carcinoma at the time of biopsy. These patients had a similar age distribution as those with concurrent carcinoma. Follow-up will be required to determine if the association with carcinoma is significant or merely a coincidence reflecting age or some other yet to be identified factor.", "contents": "Multinucleated mammary stromal giant cells: a benign lesion that simulates invasive carcinoma. Multinucleated stromal giant cells were found in breast tissue from 14 patients treated by mastectomy for carcinoma over 3 decades (1950s to 1970s). Nine cases were found in a review of 200 consecutive mastectomies (4.5%) performed in 1978. The average age was 51 years with nine patients in their 40s. Other than the age distribution, no association with marital status, family history of breast carcinoma, hormone usage, tumor type, or stage of disease was observed. This benign lesion of undetermined significance should not be misinterpreted as invasive carcinoma. Multinucleated stromal giant cells have been observed in breast specimens from patients not known to have carcinoma at the time of biopsy. These patients had a similar age distribution as those with concurrent carcinoma. Follow-up will be required to determine if the association with carcinoma is significant or merely a coincidence reflecting age or some other yet to be identified factor."}
{"id": "PMID:227562", "title": "Tumor-specific DNA sequences in human gliomas.", "content": "Utilizing the technique of hydroxyapatite chromatography, normal cellular DNAs were used to recycle off the repeat or normal sequences found in [3H]DNA copied off 70S RNA from malignant astrocytomas. The recycled [3H]DNA were then used to hybridize against DNAs from normal human brain tissues and DNAs from malignant astrocytomas or Grade IV astrocytomas. The results indicated the presence of tumor-specific DNA sequences in malignant astrocytomas, absent in normal brain tissues. The percentages were 88% and 7%, respectively. When recycled medulloblastoma 70S[3H]DNA probes were utilized against DNA'S FROM Grade IV astrocytomas and from normal brain, similar results were obtained. The respective percentages of hybridization were 67% and 7%. Thus it would appear that malignant gliomas contain tumor-specific DNA sequences which are not found in normal brain tissues.", "contents": "Tumor-specific DNA sequences in human gliomas. Utilizing the technique of hydroxyapatite chromatography, normal cellular DNAs were used to recycle off the repeat or normal sequences found in [3H]DNA copied off 70S RNA from malignant astrocytomas. The recycled [3H]DNA were then used to hybridize against DNAs from normal human brain tissues and DNAs from malignant astrocytomas or Grade IV astrocytomas. The results indicated the presence of tumor-specific DNA sequences in malignant astrocytomas, absent in normal brain tissues. The percentages were 88% and 7%, respectively. When recycled medulloblastoma 70S[3H]DNA probes were utilized against DNA'S FROM Grade IV astrocytomas and from normal brain, similar results were obtained. The respective percentages of hybridization were 67% and 7%. Thus it would appear that malignant gliomas contain tumor-specific DNA sequences which are not found in normal brain tissues."}
{"id": "PMID:227563", "title": "Primary malignant giant cell tumor of bone: a study of eight cases and review of the literature.", "content": "Eight cases of primary malignant giant cell tumor of bone were reviewed. There was a wide range in age from 17 to 76 years, with the sixth decade of life being the most common. The tumor was more frequent among females (male to female ratio--3:5). The most common sites of occurrence were in the region of the knee, with the distal end of femur and the proximal end of tibia affected in three and two cases, respectively. Pain and swelling of the involved regions were the most common complaints. The roentgenographic and pathologic features and the treatment were analyzed in detail. Although these cases were considered malignant, the follow-up periods varying from 4 to 15 years were available in six of the eight cases; only one patient died of tumor, 8 months after the surgical procedure. One patient died of unrelated cause, but the others were all alive with no evidence of disease. The pertinent literature was analyzed and examples of secondary malignant giant cell tumors of bone were compared to those of this present series to delineate differences in natural history and clinicopathologic features. It was clearly established that primary malignant giant cell tumor of bone is a separate entity with a more favorable clinical behavior, particularly if the disease process is eradicated early on either by cryosurgery, en bloc radical resection, or amputation.", "contents": "Primary malignant giant cell tumor of bone: a study of eight cases and review of the literature. Eight cases of primary malignant giant cell tumor of bone were reviewed. There was a wide range in age from 17 to 76 years, with the sixth decade of life being the most common. The tumor was more frequent among females (male to female ratio--3:5). The most common sites of occurrence were in the region of the knee, with the distal end of femur and the proximal end of tibia affected in three and two cases, respectively. Pain and swelling of the involved regions were the most common complaints. The roentgenographic and pathologic features and the treatment were analyzed in detail. Although these cases were considered malignant, the follow-up periods varying from 4 to 15 years were available in six of the eight cases; only one patient died of tumor, 8 months after the surgical procedure. One patient died of unrelated cause, but the others were all alive with no evidence of disease. The pertinent literature was analyzed and examples of secondary malignant giant cell tumors of bone were compared to those of this present series to delineate differences in natural history and clinicopathologic features. It was clearly established that primary malignant giant cell tumor of bone is a separate entity with a more favorable clinical behavior, particularly if the disease process is eradicated early on either by cryosurgery, en bloc radical resection, or amputation."}
{"id": "PMID:227564", "title": "Elevation of brain-type creatine kinase in serum from patients with carcinoma.", "content": "The brain isoenzyme of creatine kinase (CK BB) occurs in trace amounts in normal serum and is moderately increased in only a small number of non-oncological conditions. Although many tissues and tumors contain CK BB, we observed serum elevations only in certain carcinomas. Eleven patients with tissue-proven small cell anaplastic carcinoma (SCAC) of the lung had striking elevations of serum CK BB and no evidence of central nervous system (CNS) metastases. Significant increases were also observed in three cases of prostatic carcinoma with no apparent CNS involvement, and in one case each of adenocarcinoma and SCAC of the lung with proven CNS metastases. Three patients with SCAC of lung without distant metastases, three with SCAC of the esophagus with distant metastases but no known CNS involvement, and 17 patients with oncological conditions other than SCAC of the lung or adenocarcinoma of the prostate have failed to show elevation in serum CK BB activity. Serum CK BB may be useful as a diagnostic marker or indicator of metastases for some carcinomas.", "contents": "Elevation of brain-type creatine kinase in serum from patients with carcinoma. The brain isoenzyme of creatine kinase (CK BB) occurs in trace amounts in normal serum and is moderately increased in only a small number of non-oncological conditions. Although many tissues and tumors contain CK BB, we observed serum elevations only in certain carcinomas. Eleven patients with tissue-proven small cell anaplastic carcinoma (SCAC) of the lung had striking elevations of serum CK BB and no evidence of central nervous system (CNS) metastases. Significant increases were also observed in three cases of prostatic carcinoma with no apparent CNS involvement, and in one case each of adenocarcinoma and SCAC of the lung with proven CNS metastases. Three patients with SCAC of lung without distant metastases, three with SCAC of the esophagus with distant metastases but no known CNS involvement, and 17 patients with oncological conditions other than SCAC of the lung or adenocarcinoma of the prostate have failed to show elevation in serum CK BB activity. Serum CK BB may be useful as a diagnostic marker or indicator of metastases for some carcinomas."}
{"id": "PMID:227565", "title": "Interaction of factors associated with cancer of the nasopharynx.", "content": "A retrospective study of nasopharyngeal carcinoma (NPC) revealed that smoking, working under poor ventilation, use of nasal balms or oil for nasal and throat troubles, use of herbal drugs, and anti-EBV antibody titer were found statistically associated. The dural interactions of these factors to the risk of NPC were presented. Except in work conditions with poor ventilation and when herbal drugs are used, all the combinations were synergistic. The synergistic actions were especially remarkable with smoking and other factors. The possible etiological mechanisms of NPC are discussed.", "contents": "Interaction of factors associated with cancer of the nasopharynx. A retrospective study of nasopharyngeal carcinoma (NPC) revealed that smoking, working under poor ventilation, use of nasal balms or oil for nasal and throat troubles, use of herbal drugs, and anti-EBV antibody titer were found statistically associated. The dural interactions of these factors to the risk of NPC were presented. Except in work conditions with poor ventilation and when herbal drugs are used, all the combinations were synergistic. The synergistic actions were especially remarkable with smoking and other factors. The possible etiological mechanisms of NPC are discussed."}
{"id": "PMID:227566", "title": "The histology of liver tumors in oral contraceptive users observed during a national survey by the American College of Surgeons Commission on Cancer.", "content": "As part of the national survey on the tumorigenesis of oral contraceptive drugs conducted by the American College of Surgeons' Commission on Cancer, a histologic study was made of 94 cases of liver tumors in users and non-users of oral contraceptives. Pathologic criteria were established and then the slides were studied; the results were tabulated to determine the significance of each of the criteria as related to the use of contraceptives. These criteria included tumor size, peliosis hepatis, hemorrhage, necrosis, fibrosis, thrombosis, and vascular alterations of the intima and media. Cases of focal nodular hyperplasia in pill users exhibited greater vascular alterations, fibrosis, peliosis, and tumor size as compared to focal nodular hyperplasia observed in non-pill users. In addition, hemorrhage, necrosis, and peliosis were much more common in hepatic cell adenoma than in focal nodular hyperplasia. In the material reported in this series there were no hepatic cell adenoma cases observed in non-pill users. Focal nodular hyperplasia cases exhibited an overwhelmingly greater degree of vascular intimal and medial alterations than hepatic cell adenoma. The results suggest that the effects of oral contraceptives on the liver may be primarily upon the vasculature.", "contents": "The histology of liver tumors in oral contraceptive users observed during a national survey by the American College of Surgeons Commission on Cancer. As part of the national survey on the tumorigenesis of oral contraceptive drugs conducted by the American College of Surgeons' Commission on Cancer, a histologic study was made of 94 cases of liver tumors in users and non-users of oral contraceptives. Pathologic criteria were established and then the slides were studied; the results were tabulated to determine the significance of each of the criteria as related to the use of contraceptives. These criteria included tumor size, peliosis hepatis, hemorrhage, necrosis, fibrosis, thrombosis, and vascular alterations of the intima and media. Cases of focal nodular hyperplasia in pill users exhibited greater vascular alterations, fibrosis, peliosis, and tumor size as compared to focal nodular hyperplasia observed in non-pill users. In addition, hemorrhage, necrosis, and peliosis were much more common in hepatic cell adenoma than in focal nodular hyperplasia. In the material reported in this series there were no hepatic cell adenoma cases observed in non-pill users. Focal nodular hyperplasia cases exhibited an overwhelmingly greater degree of vascular intimal and medial alterations than hepatic cell adenoma. The results suggest that the effects of oral contraceptives on the liver may be primarily upon the vasculature."}
{"id": "PMID:227567", "title": "Brain metastases in disseminated germinal neoplasms: incidence and clinical course.", "content": "From July 1973, to March 1978, 139 patients with disseminated germinal neoplasms were treated with a variety of combination chemotherapy regimens. Twenty-one patients (15.1%) exhibited evidence of brain metastases at some time during their course. Central nervous system spread occurred somewhat more frequently in patients with choriocarcinoma and yolk sac histologies, although all types were at risk. This was a major cause of morbidity and mortality. However, central nervous system spread almost always occurred in patients with systemic relapse and thus did not affect overall survival. We have yet to identify a subgroup who potentially could benefit from prophylactic central nervous system therapy.", "contents": "Brain metastases in disseminated germinal neoplasms: incidence and clinical course. From July 1973, to March 1978, 139 patients with disseminated germinal neoplasms were treated with a variety of combination chemotherapy regimens. Twenty-one patients (15.1%) exhibited evidence of brain metastases at some time during their course. Central nervous system spread occurred somewhat more frequently in patients with choriocarcinoma and yolk sac histologies, although all types were at risk. This was a major cause of morbidity and mortality. However, central nervous system spread almost always occurred in patients with systemic relapse and thus did not affect overall survival. We have yet to identify a subgroup who potentially could benefit from prophylactic central nervous system therapy."}
{"id": "PMID:227568", "title": "Familial islet cell tumors in Von Hippel-Lindau's disease.", "content": "Von Hippel-Lindau's Disease is an hereditary disorder characterized by the development of hemangioblastomas of the cerebellum and retina and a variety of cystic and neoplastic lesions of other organs such as renal cell carcinoma and pheochromocytoma. In a single generation of a family with Von Hippel-Lindau's disease, all four siblings developed lesions classically associated with the complex. Additionally, two of the four developed islet cell tumors of the pancreas, one in one patient and five in the other. While a familial incidence of islet cell tumors is known in multiple endocrine adenomatosis, type I and Zollinger-Ellison syndrome, such a familial occurrence has been heretofore unrecorded in the Von Hippel-Lindau complex.", "contents": "Familial islet cell tumors in Von Hippel-Lindau's disease. Von Hippel-Lindau's Disease is an hereditary disorder characterized by the development of hemangioblastomas of the cerebellum and retina and a variety of cystic and neoplastic lesions of other organs such as renal cell carcinoma and pheochromocytoma. In a single generation of a family with Von Hippel-Lindau's disease, all four siblings developed lesions classically associated with the complex. Additionally, two of the four developed islet cell tumors of the pancreas, one in one patient and five in the other. While a familial incidence of islet cell tumors is known in multiple endocrine adenomatosis, type I and Zollinger-Ellison syndrome, such a familial occurrence has been heretofore unrecorded in the Von Hippel-Lindau complex."}
{"id": "PMID:227569", "title": "Unusual presentations of carcinoma of the right colon.", "content": "Two unusual presentations of carcinoma of the right colon are described. One of the two patients presented with a right gluteal abscess and the other presented with a colocutaneous fistula to the anterior abdominal wall at the site of a previous appendectomy scar. Despite extensive local tumor invasion of adjacent structures in both cases, all the regional lymph nodes were free of cancer and the tumors were of low-grade malignancy. A review of the literature indicates that bulky colonic tumors with extensive local invasion and negative mesenteric lymph nodes have a relatively good prognosis if adequate resection is performed.", "contents": "Unusual presentations of carcinoma of the right colon. Two unusual presentations of carcinoma of the right colon are described. One of the two patients presented with a right gluteal abscess and the other presented with a colocutaneous fistula to the anterior abdominal wall at the site of a previous appendectomy scar. Despite extensive local tumor invasion of adjacent structures in both cases, all the regional lymph nodes were free of cancer and the tumors were of low-grade malignancy. A review of the literature indicates that bulky colonic tumors with extensive local invasion and negative mesenteric lymph nodes have a relatively good prognosis if adequate resection is performed."}
{"id": "PMID:227570", "title": "Adriamycin, BCNU plus cyclophosphamide (ABC) in advanced carcinoma of the head and neck.", "content": "Forty-four patients with advanced carcinoma of the head and neck were treated with cyclophosphamide, 400 mg/m2 plus BCNU, 100 mg/m2 day 1 followed by adriamycin 40 mg/m2 day 2, with therapy repeated every 4 weeks. Of 31 evaluable patients, there were 1 complete response, and 10 partial responses (35%). Four of 8 patients without prior chemotherapy had complete or partial responses, as did 7 of 23 patients who had received prior chemotherapy. The mean survival for patients with partial responses was 8.8 months, and for patients with stable disease was 7.8 months. The mean time to progression for patients with partial responses was 5.4 months, and for patients with stable disease was 3.2 months. Granulocytopenia was the dose limiting toxicity, and patients with increasing degrees of myelosuppression appeared to have higher quality responses and longer survival. The ABC treatment program is useful in the palliative management of patients with advanced carcinoma of the head and neck.", "contents": "Adriamycin, BCNU plus cyclophosphamide (ABC) in advanced carcinoma of the head and neck. Forty-four patients with advanced carcinoma of the head and neck were treated with cyclophosphamide, 400 mg/m2 plus BCNU, 100 mg/m2 day 1 followed by adriamycin 40 mg/m2 day 2, with therapy repeated every 4 weeks. Of 31 evaluable patients, there were 1 complete response, and 10 partial responses (35%). Four of 8 patients without prior chemotherapy had complete or partial responses, as did 7 of 23 patients who had received prior chemotherapy. The mean survival for patients with partial responses was 8.8 months, and for patients with stable disease was 7.8 months. The mean time to progression for patients with partial responses was 5.4 months, and for patients with stable disease was 3.2 months. Granulocytopenia was the dose limiting toxicity, and patients with increasing degrees of myelosuppression appeared to have higher quality responses and longer survival. The ABC treatment program is useful in the palliative management of patients with advanced carcinoma of the head and neck."}
{"id": "PMID:227572", "title": "Immunohistopathologic study on carcinoembryonic antigen (CEA)-like material and immunoglobulin A in gastric malignancies.", "content": "Immunofluorescent staining for carcinoembryonic antigen (CEA)-like material and immunoglobulin A (IgA) was performed on 54 gastric specimens showing normal mucosa and various lesions including malignancy. Both CEA-like material and IgA were demonstrated in normal mucosa and benign and malignant epithelial lesions. Abnormal findings in respect to CEA-like material included staining of cell membranes with disordered pattern and increased cytoplasmic staining. Several staining characteristics for CEA-like material were shown by various types of malignant epithelial tumors. This staining provides a means of distinguishing anaplastic carcinoma from histiocytic lymphoma, as the latter does not demonstrate CEA-like material. IgA was consistently absent in anaplastic carcinomas, but was noted on the inner surface of tubular components in the differentiated adenocarcinomas, indicating functional preservation in the differentiated tumors. Immunohistochemical staining for CEA-like material and IgA is considered to be useful in the structural and functional study of gastric malignancies.", "contents": "Immunohistopathologic study on carcinoembryonic antigen (CEA)-like material and immunoglobulin A in gastric malignancies. Immunofluorescent staining for carcinoembryonic antigen (CEA)-like material and immunoglobulin A (IgA) was performed on 54 gastric specimens showing normal mucosa and various lesions including malignancy. Both CEA-like material and IgA were demonstrated in normal mucosa and benign and malignant epithelial lesions. Abnormal findings in respect to CEA-like material included staining of cell membranes with disordered pattern and increased cytoplasmic staining. Several staining characteristics for CEA-like material were shown by various types of malignant epithelial tumors. This staining provides a means of distinguishing anaplastic carcinoma from histiocytic lymphoma, as the latter does not demonstrate CEA-like material. IgA was consistently absent in anaplastic carcinomas, but was noted on the inner surface of tubular components in the differentiated adenocarcinomas, indicating functional preservation in the differentiated tumors. Immunohistochemical staining for CEA-like material and IgA is considered to be useful in the structural and functional study of gastric malignancies."}
{"id": "PMID:227573", "title": "Intracytoplasmic type A virus-like particles in angioimmunoblastic lymphadenopathy.", "content": "Virus-like particles which seemed to be oncogenic have not been observed clinically in human neoplasms. However, we found some virus-like particles in the cytoplasm of a few proliferating cells in the lymph nodes of one patient with angioimmunoblastic lymphadenopathy. These were very similar to intracytoplasmic type A particles seen in the Mazon-Pfizer monkey virus and a mammary tumor virus in a mouse.", "contents": "Intracytoplasmic type A virus-like particles in angioimmunoblastic lymphadenopathy. Virus-like particles which seemed to be oncogenic have not been observed clinically in human neoplasms. However, we found some virus-like particles in the cytoplasm of a few proliferating cells in the lymph nodes of one patient with angioimmunoblastic lymphadenopathy. These were very similar to intracytoplasmic type A particles seen in the Mazon-Pfizer monkey virus and a mammary tumor virus in a mouse."}
{"id": "PMID:227574", "title": "Liver cell dysplasia: association with hepatocellular carcinoma, cirrhosis and hepatitis B antigen carrier status.", "content": "Liver cell dysplasia was noted on histological examination of nontumorous liver from 24 of 50 (48%) black southern African males with hepatocellular carcinoma (HCC). Macronodular cirrhosis was present in 40 (80%). There was no statistically significant difference between the frequency of dysplasia in 50% of 40 cirrhotic and 40% of 10 noncirrhotic livers, or in 52.6% of 38 hepatitis B antigen (HBAg) positive and 33.3% of 12 HBAg negative HCC patients. HBAg positivity was present in 80% of 40 cirrhotic and in 60% of 10 noncirrhotic HCC patients. This lack of significant correlation between liver cell dysplasia, and both cirrhosis and HBAg positivity in HCC patients in contrast to findings in Uganda and the United States, suggests a different pathogenetic mechanism for dysplasia in southern Africa. Liver cell dysplasia in man appears to be analogous to preneoplastic experimentally-induced hyperplastic foci or areas.", "contents": "Liver cell dysplasia: association with hepatocellular carcinoma, cirrhosis and hepatitis B antigen carrier status. Liver cell dysplasia was noted on histological examination of nontumorous liver from 24 of 50 (48%) black southern African males with hepatocellular carcinoma (HCC). Macronodular cirrhosis was present in 40 (80%). There was no statistically significant difference between the frequency of dysplasia in 50% of 40 cirrhotic and 40% of 10 noncirrhotic livers, or in 52.6% of 38 hepatitis B antigen (HBAg) positive and 33.3% of 12 HBAg negative HCC patients. HBAg positivity was present in 80% of 40 cirrhotic and in 60% of 10 noncirrhotic HCC patients. This lack of significant correlation between liver cell dysplasia, and both cirrhosis and HBAg positivity in HCC patients in contrast to findings in Uganda and the United States, suggests a different pathogenetic mechanism for dysplasia in southern Africa. Liver cell dysplasia in man appears to be analogous to preneoplastic experimentally-induced hyperplastic foci or areas."}
{"id": "PMID:227575", "title": "Histologic prognostic indicators in hepatocellular carcinoma.", "content": "Survival and histologic features were studied in 80 patients with proven hepatocellular carcinoma (HCC). The overall survival was 50% at 3.5 weeks with a statistically significant drop in mortality rate after 8.5 weeks. Patients with diffuse clear-cell pattern, focal clear-cell pattern, and no clear cells in their tumors had a 50% survival rate at 14 weeks, 6 weeks, and 3 weeks respectively; the differences in survival rates were statistically significant between any pair (p less than 0.001). No correlation was found between survival and (1) cytologic differentiation, (2) histologic architecture, (3) degree of pleomorphism, or (4) presence of bile production, proteinaceous secretion, giant cells, or cytoplasmic hyaline bodies. Eosinophilic HCC with lamellar fibrosis was not observed in any of our materials. We concluded that the presence of clear cells was the only histologic feature of prognostic significance in our patients.", "contents": "Histologic prognostic indicators in hepatocellular carcinoma. Survival and histologic features were studied in 80 patients with proven hepatocellular carcinoma (HCC). The overall survival was 50% at 3.5 weeks with a statistically significant drop in mortality rate after 8.5 weeks. Patients with diffuse clear-cell pattern, focal clear-cell pattern, and no clear cells in their tumors had a 50% survival rate at 14 weeks, 6 weeks, and 3 weeks respectively; the differences in survival rates were statistically significant between any pair (p less than 0.001). No correlation was found between survival and (1) cytologic differentiation, (2) histologic architecture, (3) degree of pleomorphism, or (4) presence of bile production, proteinaceous secretion, giant cells, or cytoplasmic hyaline bodies. Eosinophilic HCC with lamellar fibrosis was not observed in any of our materials. We concluded that the presence of clear cells was the only histologic feature of prognostic significance in our patients."}
{"id": "PMID:227576", "title": "Mucinous sweat gland adenocarcinoma of eyelid: a clinicopathologic study of 21 cases with histochemical and electron microscopic observations.", "content": "This is a clinicopathologic study of 21 cases of mucinous sweat gland adenocarcinoma involving the eyelid. The tumor occurred in middle-aged adults (median age 60 years) and has a predilection for males. In this series eight patients (40%) had one or more local recurrences, one of whom died with extensive local invasion of the face after multiple recurrences in a 15-year interval. Only one patient had metastasis to the submandibular lymph nodes, which was treated by radical neck dissection. Involvement of the head, especially the face and scalp, was observed in 78% of the cases from the literature. Combining our cases with those previously reported, we found that the eyelid was involved in almost half of the cases (21 out of 45 lesions). We believe that the identification by light microscopy of a mixed population of light and dark secretory cells within the tumor lobules, the histochemical findings (presence of sialomucin and absence of iron as well as periodic acid-Schiff positive, diastase-resistant granules), and the results of ultrastructural studies support the histogenetic postulate that this mucinous adenocarcinoma is probably derived from the secretory cells of the eccrine coil. Our interpretation concurs with Headington's view of origin from the eccrine glands.", "contents": "Mucinous sweat gland adenocarcinoma of eyelid: a clinicopathologic study of 21 cases with histochemical and electron microscopic observations. This is a clinicopathologic study of 21 cases of mucinous sweat gland adenocarcinoma involving the eyelid. The tumor occurred in middle-aged adults (median age 60 years) and has a predilection for males. In this series eight patients (40%) had one or more local recurrences, one of whom died with extensive local invasion of the face after multiple recurrences in a 15-year interval. Only one patient had metastasis to the submandibular lymph nodes, which was treated by radical neck dissection. Involvement of the head, especially the face and scalp, was observed in 78% of the cases from the literature. Combining our cases with those previously reported, we found that the eyelid was involved in almost half of the cases (21 out of 45 lesions). We believe that the identification by light microscopy of a mixed population of light and dark secretory cells within the tumor lobules, the histochemical findings (presence of sialomucin and absence of iron as well as periodic acid-Schiff positive, diastase-resistant granules), and the results of ultrastructural studies support the histogenetic postulate that this mucinous adenocarcinoma is probably derived from the secretory cells of the eccrine coil. Our interpretation concurs with Headington's view of origin from the eccrine glands."}
{"id": "PMID:227577", "title": "Plasma and tumor ACTH in carcinoma of the lung.", "content": "Plasma and tissue contents of immunoreactive ACTH were determined in 100 patients undergoing surgical resection for lung cancer. ACTH was detectable (greater than 1 ng ACTH equivalent/g wet weight) tissue in 47 of 49 specimens of epidermoid carcinoma, in 15 of 17 specimens of adenocarcinoma and in 7 of 8 specimens of large cell carcinoma; the median concentrations in these three tumor types were 8, 3 and 9 ng/g, respectively. Patients with oat cell carcinoma were not considered candidates for curative resection and are not included in this series. ACTH was not detectable in 36 specimens of apparently normal lung tissue from the same lobe but distant from the tumor and ranged up to 6 ng/g in 14 other specimens. One-half of patients with epidermoid carcinoma but only one-quarter of those with adenocarcinoma had preoperative plasma levels exceeding 250 ng/L plasma. About 75% of patients survived for at least one year whether preoperative plasma levels were greater than 400 ng/L or less than 200 ng/L. In only 4 of 21 patients with preoperative levels greater than 300 ng/L did the plasma fall by at least one-half in the immediate postoperative period. It is concluded that measurement of preoperative and postoperative plasma immunoreactive ACTH does not have a prognostic value for remission or long term survival in lung cancer, probably because it is unlikely that the tumor per se is the sole source accounting for the elevated levels generally observed in this condition.", "contents": "Plasma and tumor ACTH in carcinoma of the lung. Plasma and tissue contents of immunoreactive ACTH were determined in 100 patients undergoing surgical resection for lung cancer. ACTH was detectable (greater than 1 ng ACTH equivalent/g wet weight) tissue in 47 of 49 specimens of epidermoid carcinoma, in 15 of 17 specimens of adenocarcinoma and in 7 of 8 specimens of large cell carcinoma; the median concentrations in these three tumor types were 8, 3 and 9 ng/g, respectively. Patients with oat cell carcinoma were not considered candidates for curative resection and are not included in this series. ACTH was not detectable in 36 specimens of apparently normal lung tissue from the same lobe but distant from the tumor and ranged up to 6 ng/g in 14 other specimens. One-half of patients with epidermoid carcinoma but only one-quarter of those with adenocarcinoma had preoperative plasma levels exceeding 250 ng/L plasma. About 75% of patients survived for at least one year whether preoperative plasma levels were greater than 400 ng/L or less than 200 ng/L. In only 4 of 21 patients with preoperative levels greater than 300 ng/L did the plasma fall by at least one-half in the immediate postoperative period. It is concluded that measurement of preoperative and postoperative plasma immunoreactive ACTH does not have a prognostic value for remission or long term survival in lung cancer, probably because it is unlikely that the tumor per se is the sole source accounting for the elevated levels generally observed in this condition."}
{"id": "PMID:227578", "title": "Malignant fibrous histiocytoma of the lung.", "content": "Two malignant fibrous histiocytomas arising primarily in the lung are described. The first was a large tumor of the right lower lobe in a 53-year-old man. The other tumor was found incidentally on routine roentgenograms in a 25-year-old woman and involved the left main pulmonary artery. The lesions could be resected but both patients developed early cerebral metastases. The neoplasms were predominantly fibroblastic, had a characteristic storiform pattern, and included large histiocytes with bizarre nuclei and a vacuolated cytoplasm. The ultrastructure of the cells in the fibroblastic areas was characterized by irregular nuclei and a cytoplasm with a well-developed endoplasmic reticulum and dilated cisternae. Some cells lacked the prominent endoplasmic reticulum of fibroblasts and others were characteristic histiocytes with numerous cytoplasmic lysosomes. The cases appear to be the first reported primary malignant fibrous histiocytomas of the lung.", "contents": "Malignant fibrous histiocytoma of the lung. Two malignant fibrous histiocytomas arising primarily in the lung are described. The first was a large tumor of the right lower lobe in a 53-year-old man. The other tumor was found incidentally on routine roentgenograms in a 25-year-old woman and involved the left main pulmonary artery. The lesions could be resected but both patients developed early cerebral metastases. The neoplasms were predominantly fibroblastic, had a characteristic storiform pattern, and included large histiocytes with bizarre nuclei and a vacuolated cytoplasm. The ultrastructure of the cells in the fibroblastic areas was characterized by irregular nuclei and a cytoplasm with a well-developed endoplasmic reticulum and dilated cisternae. Some cells lacked the prominent endoplasmic reticulum of fibroblasts and others were characteristic histiocytes with numerous cytoplasmic lysosomes. The cases appear to be the first reported primary malignant fibrous histiocytomas of the lung."}
{"id": "PMID:227579", "title": "Argyrophil cell carcinoma of the uterine cervix with ectopic production of ACTH, beta-MSH, serotonin, histamine, and amylase.", "content": "The case of a 38-year-old female with primary argyrophil cell carcinoma of the uterine cervix is reported. Two years after operation the patient developed widespread metastases with typical Cushing's syndrome. Microscopically, the tumor consisted of solid anaplastic cells, adenocarcinoma, and squamous cells. The plasma levels of ACTH and cortisol were elevated. Many cells of both the primary and metastatic tumors showed argyrophilia. Almost all the cells of the metastases contained numerous round secretory granules measuring about 117 micrometers in diameter. Small rod-shaped or larger round secretory granules, measuring 250 and 430 micrometers respectively, were also found in a few of these cells. The tumors in the right lung, pancreas, and kidney contained high levels of ACTH, beta-MSH, serotonin, histamine, and amylase. This is the first report of ectopic production of these five substances from argyrophil cell carcinoma of the uterine cervix.", "contents": "Argyrophil cell carcinoma of the uterine cervix with ectopic production of ACTH, beta-MSH, serotonin, histamine, and amylase. The case of a 38-year-old female with primary argyrophil cell carcinoma of the uterine cervix is reported. Two years after operation the patient developed widespread metastases with typical Cushing's syndrome. Microscopically, the tumor consisted of solid anaplastic cells, adenocarcinoma, and squamous cells. The plasma levels of ACTH and cortisol were elevated. Many cells of both the primary and metastatic tumors showed argyrophilia. Almost all the cells of the metastases contained numerous round secretory granules measuring about 117 micrometers in diameter. Small rod-shaped or larger round secretory granules, measuring 250 and 430 micrometers respectively, were also found in a few of these cells. The tumors in the right lung, pancreas, and kidney contained high levels of ACTH, beta-MSH, serotonin, histamine, and amylase. This is the first report of ectopic production of these five substances from argyrophil cell carcinoma of the uterine cervix."}
{"id": "PMID:227580", "title": "Mucin-producing carcinoid (\"composite tumor\") of upper third of esophagus: a variant of carcinoid tumor.", "content": "An unusual upper esophageal polypoid tumor was found to be predominantly a carcinoid tumor and in part a mucin-producing adenocarcinoma. A review of literature showed this to be a unique tumor in this location.", "contents": "Mucin-producing carcinoid (\"composite tumor\") of upper third of esophagus: a variant of carcinoid tumor. An unusual upper esophageal polypoid tumor was found to be predominantly a carcinoid tumor and in part a mucin-producing adenocarcinoma. A review of literature showed this to be a unique tumor in this location."}
{"id": "PMID:227581", "title": "Remission of pure red cell aplasia associated with nonthymic malignancy.", "content": "Two patients with acquired pure red cell aplasia associated with malignancy are presented. One patient has breast cancer and the other had poorly differentiated nodular lymphoma; neither patient had evidence of a serum inhibitor of hemoglobin synthesis and both achieved complete hematologic remission following prolonged immunosuppressive therapy. The literature describing the association of pure red cell aplasia and nonthymic malignancy is reviewed and potential for responsiveness discussed.", "contents": "Remission of pure red cell aplasia associated with nonthymic malignancy. Two patients with acquired pure red cell aplasia associated with malignancy are presented. One patient has breast cancer and the other had poorly differentiated nodular lymphoma; neither patient had evidence of a serum inhibitor of hemoglobin synthesis and both achieved complete hematologic remission following prolonged immunosuppressive therapy. The literature describing the association of pure red cell aplasia and nonthymic malignancy is reviewed and potential for responsiveness discussed."}
{"id": "PMID:227583", "title": "Inactivation of membrane-bound (Na+ +K+)-ATPase of Yoshida sarcoma cells and cobra venom cytotoxin complex with the glycolipid components of the enzyme system.", "content": "The molecular mechanisms involved in the inactivation of (Na+ + K+)-stimulated ATPase of Yoshida sarcoma cells by a cytotoxic protein (P6) from cobra venom have been examined. The overall data obtained using purified (Na+ + K+)-stimulated ATPase of Yoshida sarcoma cells suggest that cytotoxin P6 combines with phosphatidyl serine and a glycolipid which are closely associated with (Na+ + K+)-stimulated ATPase which in turn may lead to the inactivation of the enzyme in this cell system.", "contents": "Inactivation of membrane-bound (Na+ +K+)-ATPase of Yoshida sarcoma cells and cobra venom cytotoxin complex with the glycolipid components of the enzyme system. The molecular mechanisms involved in the inactivation of (Na+ + K+)-stimulated ATPase of Yoshida sarcoma cells by a cytotoxic protein (P6) from cobra venom have been examined. The overall data obtained using purified (Na+ + K+)-stimulated ATPase of Yoshida sarcoma cells suggest that cytotoxin P6 combines with phosphatidyl serine and a glycolipid which are closely associated with (Na+ + K+)-stimulated ATPase which in turn may lead to the inactivation of the enzyme in this cell system."}
{"id": "PMID:227584", "title": "In vivo infectivity of the fibrotropic C-type viral isolates from C57BL/Ka mice.", "content": "Of the three fibrotropic C-type viral isolates from C57BL/Ka mice, only the BL/Ka(B) virus is capable of infecting normal hematopoietic and lymphoid cell populations of C57BL/Ka mice in vivo, and none are tumorigenic. Inoculation of this virus alone into neonates resulted in transient replication in the bone marrow, spleen, and occasionally the thymus. Thymocytes could, however, be permanently infected in such animals if BL/Ka(B) were coinoculated with the xenotropic BL/Ka(X) virus. Neonatal injection of BL/Ka(B) prior to fractionated wholebody irradiation yielded an increase in the percentage of virus-productive radiogenic lymphomas and a decrease in incidence of such tumors. Injection of BL/Ka(B) into normal adult C57BL/Ka mice did not yield overt expression of virus replication in any of the tissues tested; latent infection could, however, be detected in the marrow and in the reticuloepithelium of the thymus. Whole-body X-irradiation of adults with 400 rads partially restored the neonatal susceptibility of bone marrow cells to infection by the isolate. BL/Ka(B) injection after fractionated whole-body irradiation of weanling C57BL/Ka mice increased the percentage of virus-positive lymphomas and revealed that a bone marrow cell subpopulation permissive for infection by the virus increases greatly in abundance soon after irradiation.", "contents": "In vivo infectivity of the fibrotropic C-type viral isolates from C57BL/Ka mice. Of the three fibrotropic C-type viral isolates from C57BL/Ka mice, only the BL/Ka(B) virus is capable of infecting normal hematopoietic and lymphoid cell populations of C57BL/Ka mice in vivo, and none are tumorigenic. Inoculation of this virus alone into neonates resulted in transient replication in the bone marrow, spleen, and occasionally the thymus. Thymocytes could, however, be permanently infected in such animals if BL/Ka(B) were coinoculated with the xenotropic BL/Ka(X) virus. Neonatal injection of BL/Ka(B) prior to fractionated wholebody irradiation yielded an increase in the percentage of virus-productive radiogenic lymphomas and a decrease in incidence of such tumors. Injection of BL/Ka(B) into normal adult C57BL/Ka mice did not yield overt expression of virus replication in any of the tissues tested; latent infection could, however, be detected in the marrow and in the reticuloepithelium of the thymus. Whole-body X-irradiation of adults with 400 rads partially restored the neonatal susceptibility of bone marrow cells to infection by the isolate. BL/Ka(B) injection after fractionated whole-body irradiation of weanling C57BL/Ka mice increased the percentage of virus-positive lymphomas and revealed that a bone marrow cell subpopulation permissive for infection by the virus increases greatly in abundance soon after irradiation."}
{"id": "PMID:227585", "title": "Prolactin receptors in human breast cancer cells in long-term tissue culture.", "content": "Prolactin receptors have been identified for the first time in a number of human breast cancer cell lines and a normal human breast cell line maintained in long-term tissue culture. Optimal conditions for determining the binding of 125I-labeled human prolactin to these cells were established. Five different tumor cell lines have different content of prolactin receptors ranging from 2,300 to 26,000 sites/cell. All tumor cell lines contained more prolactin receptors than does one normal breast cell line (1700 sites/cell). The prolactin receptors in these human mammary tumor cells not only bind human prolactin but also recognize other lactogenic hormones such as human growth hormone, human placental lactogen, and sheep prolactin, but not animal growth hormone, which are not lactogenic. The affinity (Ka) of binding of human prolactin to these cells is 4 x 10(9) M-1 (Kd = 2.5 x 10(-10)M). The hormone specificity and affinity for hormone of these human mammary tumor cells are very similar to that found for the rabbit mammary gland. These human mammary tumor cell lines in long-term culture should prove very useful to study the biology of prolactin receptors in living human cells and the role of prolactin in the tumorigenesis of the human breast.", "contents": "Prolactin receptors in human breast cancer cells in long-term tissue culture. Prolactin receptors have been identified for the first time in a number of human breast cancer cell lines and a normal human breast cell line maintained in long-term tissue culture. Optimal conditions for determining the binding of 125I-labeled human prolactin to these cells were established. Five different tumor cell lines have different content of prolactin receptors ranging from 2,300 to 26,000 sites/cell. All tumor cell lines contained more prolactin receptors than does one normal breast cell line (1700 sites/cell). The prolactin receptors in these human mammary tumor cells not only bind human prolactin but also recognize other lactogenic hormones such as human growth hormone, human placental lactogen, and sheep prolactin, but not animal growth hormone, which are not lactogenic. The affinity (Ka) of binding of human prolactin to these cells is 4 x 10(9) M-1 (Kd = 2.5 x 10(-10)M). The hormone specificity and affinity for hormone of these human mammary tumor cells are very similar to that found for the rabbit mammary gland. These human mammary tumor cell lines in long-term culture should prove very useful to study the biology of prolactin receptors in living human cells and the role of prolactin in the tumorigenesis of the human breast."}
{"id": "PMID:227586", "title": "Hormone-dependent growth of a rat chondrosarcoma in vivo.", "content": "The importance of various hormonal factors in the growth of a transplantable chondrosarcoma has been studied in vivo. Tumor growth was reduced by 95% in adrenalectomized or hypophysectomized rats as compared to normal animals. The number of tumors developing in either adrenalectomized or hypophysectomized rats was reduced more in male than in female rats. However, ovariectomy or orchiectomy did not alter the growth of the tumor. The inhibition of tumor growth in adrenalectomized and hypophysectomized animals was only observed after the first 10 days following inoculation. Cortisone (4-pregnen-17 alpha,21-diol-3,11,20-trione) administration fully restored tumor growth in adrenalectomized animals while adrenocorticotropic hormone or growth hormone were only partially effective in supporting tumor growth in hypophysectomized animals. High-affinity glucocorticoid receptors (7 to 10S) were present in the cytosls prepared from the tumor cells and were found to be increased in tumors from adrenalectomized animals. These results indicate that the growth of this chondrosarcoma is strongly dependent upon endocrine factors of adrenal and pituitary origin.", "contents": "Hormone-dependent growth of a rat chondrosarcoma in vivo. The importance of various hormonal factors in the growth of a transplantable chondrosarcoma has been studied in vivo. Tumor growth was reduced by 95% in adrenalectomized or hypophysectomized rats as compared to normal animals. The number of tumors developing in either adrenalectomized or hypophysectomized rats was reduced more in male than in female rats. However, ovariectomy or orchiectomy did not alter the growth of the tumor. The inhibition of tumor growth in adrenalectomized and hypophysectomized animals was only observed after the first 10 days following inoculation. Cortisone (4-pregnen-17 alpha,21-diol-3,11,20-trione) administration fully restored tumor growth in adrenalectomized animals while adrenocorticotropic hormone or growth hormone were only partially effective in supporting tumor growth in hypophysectomized animals. High-affinity glucocorticoid receptors (7 to 10S) were present in the cytosls prepared from the tumor cells and were found to be increased in tumors from adrenalectomized animals. These results indicate that the growth of this chondrosarcoma is strongly dependent upon endocrine factors of adrenal and pituitary origin."}
{"id": "PMID:227587", "title": "Relationship between inhibition of protein methylase I and inhibition of Rous sarcoma virus-induced cell transformation.", "content": "A correlation was found between inhibition of protein methylase I and inhibition of virus-induced cell transformation by structural analogs of S-adenosylhomocysteine; all good inhibitors of this enzyme are also good inhibitors of Rous sarcoma virus-induced chicke embryo fibroblast transformation. The inhibitory effect of these analogs was similar on enzymes from normal and transformed cells; no significant variation of the inhibition constants was observed after purification of protein methylase I. From the kinetic constants obtained, a structure-activity relationship can be established for protein methylase I.", "contents": "Relationship between inhibition of protein methylase I and inhibition of Rous sarcoma virus-induced cell transformation. A correlation was found between inhibition of protein methylase I and inhibition of virus-induced cell transformation by structural analogs of S-adenosylhomocysteine; all good inhibitors of this enzyme are also good inhibitors of Rous sarcoma virus-induced chicke embryo fibroblast transformation. The inhibitory effect of these analogs was similar on enzymes from normal and transformed cells; no significant variation of the inhibition constants was observed after purification of protein methylase I. From the kinetic constants obtained, a structure-activity relationship can be established for protein methylase I."}
{"id": "PMID:227588", "title": "Metabolism of three radiolabeled pancreatic carcinogenic nitrosamines in hamsters and rats.", "content": "The in vivo metabolism and disposition of three radiolabeled N-nitrosamines which are carcinogenic for the pancreas of the hamster but not the rat have been examined. N-[1-14C]Nitrosobis(2-oxopropyl)amine (BOP), N-[1-14C]nitrosobis(2-hydroxypropyl)amine (BHP), and their suggested proximate pancreatic carcinogenic metabolite N-[1-14C]nitroso-(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) were metabolized and exhaled as 14CO2 to various extents somewhat proportional to their carcinogenic potency. More than 50% of the dose of BOP and HPOP was exhaled as 14CO2, whereas 26% of BHP was excreted this way, and 40% of BHP was excreted unchanged in the urine. Administered BOP was excreted to a small extent in the urine of both species as HPOP and BHP. No other nitrosamine metabolites were detected in urine. HPOP and BHP were detected in the pancreatic juice and bile of both species after administration of BOP and BHP. The results suggest that pancreatic ductular carcinogenesis in the hamster as a result of exposure to BOP is not due to secretion of carcinogenic metabolities in the pancreatic juice or reflux of bile containing nitrosamine metabolites into the ducts. Carcinogen metabolic activation appears to be by an oxidative pathway.", "contents": "Metabolism of three radiolabeled pancreatic carcinogenic nitrosamines in hamsters and rats. The in vivo metabolism and disposition of three radiolabeled N-nitrosamines which are carcinogenic for the pancreas of the hamster but not the rat have been examined. N-[1-14C]Nitrosobis(2-oxopropyl)amine (BOP), N-[1-14C]nitrosobis(2-hydroxypropyl)amine (BHP), and their suggested proximate pancreatic carcinogenic metabolite N-[1-14C]nitroso-(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) were metabolized and exhaled as 14CO2 to various extents somewhat proportional to their carcinogenic potency. More than 50% of the dose of BOP and HPOP was exhaled as 14CO2, whereas 26% of BHP was excreted this way, and 40% of BHP was excreted unchanged in the urine. Administered BOP was excreted to a small extent in the urine of both species as HPOP and BHP. No other nitrosamine metabolites were detected in urine. HPOP and BHP were detected in the pancreatic juice and bile of both species after administration of BOP and BHP. The results suggest that pancreatic ductular carcinogenesis in the hamster as a result of exposure to BOP is not due to secretion of carcinogenic metabolities in the pancreatic juice or reflux of bile containing nitrosamine metabolites into the ducts. Carcinogen metabolic activation appears to be by an oxidative pathway."}
{"id": "PMID:227589", "title": "Enhanced collagenase production by fibroblasts derived from human basal cell carcinomas.", "content": "Fibroblast cultures derived from human basal cell carcinomas demonstrated an increased capacity to synthesize and secrete collagenase. Although the levels of collagenase were up to 8-fold greater than those of normal control cell lines, this phenotypic trait was not permanent and was expressed only for a few passages following primary explanation. The basal cell carcinoma fibroblast collagenase was secreted as a proenzyme. The kinetics of activation and the catalytic efficiency of the basal cell carcinoma fibroblast enzyme were equal to control collagenase, indicating that increased activity was due to increased synthesis of enzyme protein. Increased synthesis of collagenase was not due either to altered cell growth or to an overall increase in protein synthesis. Furthermore, synthesis of another major protein, of another major protein, collagen, was not enhanced. The data suggest that the tumors may have stimulated adjacent fibroblasts to produce more collagenase which is of importance in tumor invasion.", "contents": "Enhanced collagenase production by fibroblasts derived from human basal cell carcinomas. Fibroblast cultures derived from human basal cell carcinomas demonstrated an increased capacity to synthesize and secrete collagenase. Although the levels of collagenase were up to 8-fold greater than those of normal control cell lines, this phenotypic trait was not permanent and was expressed only for a few passages following primary explanation. The basal cell carcinoma fibroblast collagenase was secreted as a proenzyme. The kinetics of activation and the catalytic efficiency of the basal cell carcinoma fibroblast enzyme were equal to control collagenase, indicating that increased activity was due to increased synthesis of enzyme protein. Increased synthesis of collagenase was not due either to altered cell growth or to an overall increase in protein synthesis. Furthermore, synthesis of another major protein, of another major protein, collagen, was not enhanced. The data suggest that the tumors may have stimulated adjacent fibroblasts to produce more collagenase which is of importance in tumor invasion."}
{"id": "PMID:227590", "title": "Relationship between Rous sarcoma virus-induced expression of membrane antigen and phenotypic transformation.", "content": "Rous sarcoma virus-transformed hamster BHK fibroblasts express a virus-induced cell surface antigen undetectable in cells either transformed by unrelated viruses or infected by transformation-defective strains of Rous sarcoma virus. To clarify whether this antigen plays any role in the process of malignant transformation or is expressed at the cell surface only as a consequence of the acquisition of the transformed phenotype, we have investigated its expression at the cell surface of Rous sarcoma virus-transformed BHK cells treated with dibutyryl cyclic adenosine 3':5'-monophosphate and at the surface of parental BHK cells transiently transformed by the tumor promoter phorbol myristate acetate. In the dibutyryl cyclic adenosine 3':5'-monophosphate-treated cells, in which most of the parameters of the transformed phenotype are reverted to normality, but the product of the transforming gene is still present, virus-induced cell surface antigen is expressed. In the mirror experiment, this antigen is not expressed by phenotypically transformed but genetically normal phorbol myristate acetate-treated cells. It is concluded that the tumor membrane antigen studied is intimately associated with the expression of the function(s) controlled by the transforming gene.", "contents": "Relationship between Rous sarcoma virus-induced expression of membrane antigen and phenotypic transformation. Rous sarcoma virus-transformed hamster BHK fibroblasts express a virus-induced cell surface antigen undetectable in cells either transformed by unrelated viruses or infected by transformation-defective strains of Rous sarcoma virus. To clarify whether this antigen plays any role in the process of malignant transformation or is expressed at the cell surface only as a consequence of the acquisition of the transformed phenotype, we have investigated its expression at the cell surface of Rous sarcoma virus-transformed BHK cells treated with dibutyryl cyclic adenosine 3':5'-monophosphate and at the surface of parental BHK cells transiently transformed by the tumor promoter phorbol myristate acetate. In the dibutyryl cyclic adenosine 3':5'-monophosphate-treated cells, in which most of the parameters of the transformed phenotype are reverted to normality, but the product of the transforming gene is still present, virus-induced cell surface antigen is expressed. In the mirror experiment, this antigen is not expressed by phenotypically transformed but genetically normal phorbol myristate acetate-treated cells. It is concluded that the tumor membrane antigen studied is intimately associated with the expression of the function(s) controlled by the transforming gene."}
{"id": "PMID:227591", "title": "Effects of 12-O-tetradecanoylphorbol-13-acetate and mezerein on epidermal ornithine decarboxylase activity, isoproterenol-stimulated levels of cyclic adenosine 3':5'-monophosphate, and induction of mouse skin tumors in vivo.", "content": "The tumor promoter 12-O-tetradecanoylphorbol-13-acetate and the antileukemic agent mezerein are diterpene esters of plant origin with certain structural similarities. Both compounds, when applied topically to mouse skin, were equipotent on a molar basis in inducing hyperplasia, inflammation, and ornithine decarboxylase activity, as well as in reducing cyclic adenosine 3':5'-monophosphate accumulation in response to beta-adrenergic stimulation. In contrast, mezerein was much less effective as a tumor promoter; the phorbol ester at 8.5 nmol/application yielded 78-fold more tumors than did 8.5 nmol mezerein per application to similarly initiated SENCAR mice. The superiority of the phorbol ester was nearly as great in CD-1 mice.", "contents": "Effects of 12-O-tetradecanoylphorbol-13-acetate and mezerein on epidermal ornithine decarboxylase activity, isoproterenol-stimulated levels of cyclic adenosine 3':5'-monophosphate, and induction of mouse skin tumors in vivo. The tumor promoter 12-O-tetradecanoylphorbol-13-acetate and the antileukemic agent mezerein are diterpene esters of plant origin with certain structural similarities. Both compounds, when applied topically to mouse skin, were equipotent on a molar basis in inducing hyperplasia, inflammation, and ornithine decarboxylase activity, as well as in reducing cyclic adenosine 3':5'-monophosphate accumulation in response to beta-adrenergic stimulation. In contrast, mezerein was much less effective as a tumor promoter; the phorbol ester at 8.5 nmol/application yielded 78-fold more tumors than did 8.5 nmol mezerein per application to similarly initiated SENCAR mice. The superiority of the phorbol ester was nearly as great in CD-1 mice."}
{"id": "PMID:227593", "title": "Putrescine as a biochemical marker of malignant brain tumors.", "content": "Putrescine, spermidine, and spermine levels were determined in normal brain and central nervous system-related tumor tissues obtained at operation from 50 patients. The biochemical data were correlated with morphological histopathological descriptions of the same tissues. There was little variation in putrescine levels in normal cerebral cortical tissue. Subcortical white matter had lower putrescine but higher spermidine content than those of the overlying cortex. Putrescine levels were elevated in all astrocytomas assayed, and the magnitude of this elevation was proportional to the malignancy of the tumor as determined by histopathological criteria. In contradistinction, putrescine content of \"benign\" tumors was generally equal to or lower than that of the normal cerebral cortex. Spermidine and spermine levels varied widely in the tumors assayed and did not correlate with criteria of malignancy. It is concluded that putrescine may be a good biochemical marker of malignancy in central nervous system-related tumors.", "contents": "Putrescine as a biochemical marker of malignant brain tumors. Putrescine, spermidine, and spermine levels were determined in normal brain and central nervous system-related tumor tissues obtained at operation from 50 patients. The biochemical data were correlated with morphological histopathological descriptions of the same tissues. There was little variation in putrescine levels in normal cerebral cortical tissue. Subcortical white matter had lower putrescine but higher spermidine content than those of the overlying cortex. Putrescine levels were elevated in all astrocytomas assayed, and the magnitude of this elevation was proportional to the malignancy of the tumor as determined by histopathological criteria. In contradistinction, putrescine content of \"benign\" tumors was generally equal to or lower than that of the normal cerebral cortex. Spermidine and spermine levels varied widely in the tumors assayed and did not correlate with criteria of malignancy. It is concluded that putrescine may be a good biochemical marker of malignancy in central nervous system-related tumors."}
{"id": "PMID:227595", "title": "Sequence homology of nucleic acids from human breast cancer cells and complementary DNA's from murine mammary tumor virus and Mason-Pfizer monkey virus.", "content": "Simultaneous presence of murine mammary tumor virus- and Mason-Pfizer monkey virus-specific sequences has been detected in nucleic acids isolated from some human breast tumors and from MCF-7 cells, a well-characterized human breast cancer cell line. Carefully characterized long complementary DNA transcripts were used in the molecular hybridization experiments. From the data that are presently available, it would appear that when homology is detected with one of the mammary tumor probes the other also generally shows shows homology. Among all the complementary DNA-RNA hybrids only three, all murine mammary tumor virus hybrids, show Tm values close to 80 degrees. The rest of the hybrids are low melting with shallow slopes for their Crt curves, indicating partial and imperfect hybrids in the majority of cases. Low levels of weak hybrid formation are also detectable with the tumor DNA's. The present experiments cannot ascertain whether the hybridizing sequences from Mason-Pfizer monkey virus and murine mammary tumor virus code for specific viral functions in their natural hosts. Annealing experiments using gene specific cDNA's would be required for fully characterizing these sequences.", "contents": "Sequence homology of nucleic acids from human breast cancer cells and complementary DNA's from murine mammary tumor virus and Mason-Pfizer monkey virus. Simultaneous presence of murine mammary tumor virus- and Mason-Pfizer monkey virus-specific sequences has been detected in nucleic acids isolated from some human breast tumors and from MCF-7 cells, a well-characterized human breast cancer cell line. Carefully characterized long complementary DNA transcripts were used in the molecular hybridization experiments. From the data that are presently available, it would appear that when homology is detected with one of the mammary tumor probes the other also generally shows shows homology. Among all the complementary DNA-RNA hybrids only three, all murine mammary tumor virus hybrids, show Tm values close to 80 degrees. The rest of the hybrids are low melting with shallow slopes for their Crt curves, indicating partial and imperfect hybrids in the majority of cases. Low levels of weak hybrid formation are also detectable with the tumor DNA's. The present experiments cannot ascertain whether the hybridizing sequences from Mason-Pfizer monkey virus and murine mammary tumor virus code for specific viral functions in their natural hosts. Annealing experiments using gene specific cDNA's would be required for fully characterizing these sequences."}
{"id": "PMID:227596", "title": "Evaluation of impaired triglyceride fatty acid transport and oxidation for the detection of cancer in mice.", "content": "We have tested the hypothesis proposed by Costa, Lyles, and Ullrich. (Effect of Human and Experimental Cancer on the Conversion of 14C Tripalmitin to 14CO2. Cancer (Phila.), 38:1259-1265, 1976) that the transport and/or oxidation of triglyceride fatty acids is markedly impaired in rodents bearing a growing s.c. carcinoma. Specifically, we have tested whether oxidation of triglyceride fatty acids is depressed in cancer-bearing animals. Mice inoculated s.c. with Ehrlich carcinoma cells were given injections (i.v. and i.p.) of 14C-labeled triglyceride fatty acids prepared as very-low-density lipoproteins by physiological methods or (i.p.) with [-14C]tripalmitin dissolved in peanut oil during both early (3 to 4 days) and advanced (7 to 8 weeks) stages of tumor growth. Specific activity of the expired 14CO2 was measured for periods ranging from 1 to 7 hr following injections. Because cancer-bearing mice can become severely hypertriglyceridemic, plasma triglyceride pool sizes were also measured during each experiment to account for the effects of possible differential dilution of the tracers. At no instance did we find any significant differences between specific activities of expired 14CO2 or plasma triglyceride pool sizes of the cancer-bearing animals and controls. Thus, a cancer-induced impairment of triglyceride fatty acid transport and metabolism to CO2, such as reported by Costa et al., does not seem to be a universal phenomenon in rodents.", "contents": "Evaluation of impaired triglyceride fatty acid transport and oxidation for the detection of cancer in mice. We have tested the hypothesis proposed by Costa, Lyles, and Ullrich. (Effect of Human and Experimental Cancer on the Conversion of 14C Tripalmitin to 14CO2. Cancer (Phila.), 38:1259-1265, 1976) that the transport and/or oxidation of triglyceride fatty acids is markedly impaired in rodents bearing a growing s.c. carcinoma. Specifically, we have tested whether oxidation of triglyceride fatty acids is depressed in cancer-bearing animals. Mice inoculated s.c. with Ehrlich carcinoma cells were given injections (i.v. and i.p.) of 14C-labeled triglyceride fatty acids prepared as very-low-density lipoproteins by physiological methods or (i.p.) with [-14C]tripalmitin dissolved in peanut oil during both early (3 to 4 days) and advanced (7 to 8 weeks) stages of tumor growth. Specific activity of the expired 14CO2 was measured for periods ranging from 1 to 7 hr following injections. Because cancer-bearing mice can become severely hypertriglyceridemic, plasma triglyceride pool sizes were also measured during each experiment to account for the effects of possible differential dilution of the tracers. At no instance did we find any significant differences between specific activities of expired 14CO2 or plasma triglyceride pool sizes of the cancer-bearing animals and controls. Thus, a cancer-induced impairment of triglyceride fatty acid transport and metabolism to CO2, such as reported by Costa et al., does not seem to be a universal phenomenon in rodents."}
{"id": "PMID:227598", "title": "cis-Dichlorodiammineplatinum(II) and VP-16-213: an active induction regimen for small cell carcinoma of the lung.", "content": "Thirty-eight patients with small cell carcinoma and no prior therapy were treated with a combination chemotherapy program including 60 mg/m2 of cis-dichlorodiammineplatinum(II) (cis-platinum) iv on Days 1 and 22 and 120 mg/m2 of VP-16-213 iv on Days 4, 6, 8, 25, 27, and 29. This was followed by 1000 mg/m2 of cyclophosphamide, 40 mg/m2 of Adriamycin, and 1.4 mg/m2 of vincristine, all given iv on Days 42, 63, 84, and 105. The program was then recycled, with cis-platinum and VP-16-213 beginning on Day 126 and the regimen repeated as above. All patients received prophylactic whole-brain radiation (usually at a dose of 3000 rads in ten fractions) between Days 42 and 63. The projected duration of treatment is 18 months in the absence of relapse. In 21 patients with limited disease, the complete response rate was 52% (5.75+--15.25+ months) and the partial remission rate was 48% (2.25--10.5 months). The extensive-disease group showed a complete remission rate of 41% (4.75--11+ months) and a partial remission rate of 47% (3.75--11.5+ months). Response to therapy with cis-platinum and VP-16-213 was very rapid and invariably maximal by the end of the 6-week induction period. Survival for the limited-disease group appears encouraging but followup time is insufficient. Toxicity included nausea and vomiting, myelosuppression, alopecia, and renal insufficiency which was dose-limiting in two patients. The cis-platinum and VP-16-213 combination is clearly an active induction regimen in small cell carcinoma of the lung, but whether it will play a role in increasing long-term survival rates remains to be seen.", "contents": "cis-Dichlorodiammineplatinum(II) and VP-16-213: an active induction regimen for small cell carcinoma of the lung. Thirty-eight patients with small cell carcinoma and no prior therapy were treated with a combination chemotherapy program including 60 mg/m2 of cis-dichlorodiammineplatinum(II) (cis-platinum) iv on Days 1 and 22 and 120 mg/m2 of VP-16-213 iv on Days 4, 6, 8, 25, 27, and 29. This was followed by 1000 mg/m2 of cyclophosphamide, 40 mg/m2 of Adriamycin, and 1.4 mg/m2 of vincristine, all given iv on Days 42, 63, 84, and 105. The program was then recycled, with cis-platinum and VP-16-213 beginning on Day 126 and the regimen repeated as above. All patients received prophylactic whole-brain radiation (usually at a dose of 3000 rads in ten fractions) between Days 42 and 63. The projected duration of treatment is 18 months in the absence of relapse. In 21 patients with limited disease, the complete response rate was 52% (5.75+--15.25+ months) and the partial remission rate was 48% (2.25--10.5 months). The extensive-disease group showed a complete remission rate of 41% (4.75--11+ months) and a partial remission rate of 47% (3.75--11.5+ months). Response to therapy with cis-platinum and VP-16-213 was very rapid and invariably maximal by the end of the 6-week induction period. Survival for the limited-disease group appears encouraging but followup time is insufficient. Toxicity included nausea and vomiting, myelosuppression, alopecia, and renal insufficiency which was dose-limiting in two patients. The cis-platinum and VP-16-213 combination is clearly an active induction regimen in small cell carcinoma of the lung, but whether it will play a role in increasing long-term survival rates remains to be seen."}
{"id": "PMID:227603", "title": "Antigenic variation in visna virus.", "content": "Two antigenic variants of visna virus were isolated sequentially from a single sheep inoculated with a plaque-purified strain of virus designated 1514. The genetically stable variants, LV1-1 and LV1-4, are of two classes: LV1-1 is partially neutralized by antibody to the inoculum strain 1514, while LV1-4 is not neutralized by antibody to 1514. The genetic mechanism responsible for generating the antigenic variants was investigated by comparing the chymotryptic and tryptic maps of the envelope glycoprotein gp135 and core polypeptides (p30, p16, p14), and by comparing the pattern of large oligonucleotides produced by digestion of the RNAs by T1 ribonuclease. We show that only the peptide maps of gp135 differ among strains, that the number of peptide fragments altered is small and that gp135 is the polypeptide that elicits neutralizing antibody. The maps of the RNAs are identical. We conclude that mutation in the glycoprotein gene rather than recombination is more probably responsible for antigenic variation, and speculate on the special aspects of visna virus replication relevant to this phenomenon.", "contents": "Antigenic variation in visna virus. Two antigenic variants of visna virus were isolated sequentially from a single sheep inoculated with a plaque-purified strain of virus designated 1514. The genetically stable variants, LV1-1 and LV1-4, are of two classes: LV1-1 is partially neutralized by antibody to the inoculum strain 1514, while LV1-4 is not neutralized by antibody to 1514. The genetic mechanism responsible for generating the antigenic variants was investigated by comparing the chymotryptic and tryptic maps of the envelope glycoprotein gp135 and core polypeptides (p30, p16, p14), and by comparing the pattern of large oligonucleotides produced by digestion of the RNAs by T1 ribonuclease. We show that only the peptide maps of gp135 differ among strains, that the number of peptide fragments altered is small and that gp135 is the polypeptide that elicits neutralizing antibody. The maps of the RNAs are identical. We conclude that mutation in the glycoprotein gene rather than recombination is more probably responsible for antigenic variation, and speculate on the special aspects of visna virus replication relevant to this phenomenon."}
{"id": "PMID:227600", "title": "Germ cell tumors of the testis.", "content": "The histologic patterns of the various germ cell tumors of the testis are reviewed and these tumors have been defined and classified according to the World Health Organization criteria. The importance of obtaining adequate sections of the primary and metastatic tumors is stressed and more extensive use of the World Health Organization classification of testicular tumors is encouraged so that meaningful comparisons may be made between different centers treating these patients.", "contents": "Germ cell tumors of the testis. The histologic patterns of the various germ cell tumors of the testis are reviewed and these tumors have been defined and classified according to the World Health Organization criteria. The importance of obtaining adequate sections of the primary and metastatic tumors is stressed and more extensive use of the World Health Organization classification of testicular tumors is encouraged so that meaningful comparisons may be made between different centers treating these patients."}
{"id": "PMID:227599", "title": "Phase II trial of cis-dichlorodiammineplatinum(II) in advanced malignant lymphoma and small cell lung cancer: preliminary results.", "content": "In an ongoing cooperative study of the Cancer and Acute Leukemia Group B, 21 evaluable patients with advanced malignant lymphomas were treated with 70 mg/m2 of cis-dichlorodiammineplatinum(II) (cis-platinum) once every 3 weeks. All patients had received extensive prior therapy. Partial remission was obtained in two of seven patients with Hodgkin's disease, for 1+ and 7 months, and in three of 14 patients with non-Hodgkin's lymphoma, for 2, 2+, and 2.5 months. In another ongoing trial, 11 patients with advanced, pretreated small cell cancer of the lung received 80 mg/m2 of cis-platinum once every 3 weeks. Four patients achieved partial remissions. These lasted 2+ and 2.5 months in the two patients evaluable for duration of response. Two further clear-cut tumor regressions were noted. The major toxic effects were myelosuppression and vomiting. In the second trial, one case of probable drug-related fatal nephrotoxicity was encountered despite optimal forced diuresis with mannitol and furosemide. cis-Platinum definitely warrants further evaluation in these diseases because of significant effectiveness even after extensive prior treatment.", "contents": "Phase II trial of cis-dichlorodiammineplatinum(II) in advanced malignant lymphoma and small cell lung cancer: preliminary results. In an ongoing cooperative study of the Cancer and Acute Leukemia Group B, 21 evaluable patients with advanced malignant lymphomas were treated with 70 mg/m2 of cis-dichlorodiammineplatinum(II) (cis-platinum) once every 3 weeks. All patients had received extensive prior therapy. Partial remission was obtained in two of seven patients with Hodgkin's disease, for 1+ and 7 months, and in three of 14 patients with non-Hodgkin's lymphoma, for 2, 2+, and 2.5 months. In another ongoing trial, 11 patients with advanced, pretreated small cell cancer of the lung received 80 mg/m2 of cis-platinum once every 3 weeks. Four patients achieved partial remissions. These lasted 2+ and 2.5 months in the two patients evaluable for duration of response. Two further clear-cut tumor regressions were noted. The major toxic effects were myelosuppression and vomiting. In the second trial, one case of probable drug-related fatal nephrotoxicity was encountered despite optimal forced diuresis with mannitol and furosemide. cis-Platinum definitely warrants further evaluation in these diseases because of significant effectiveness even after extensive prior treatment."}
{"id": "PMID:227604", "title": "Characterization of different tumor antigens present in cells transformed by simian virus 40.", "content": "In addition to large T and small t antigens, cells transformed by simian virus 40 (SV40) commonly contain other proteins which specifically immunoprecipitate with SV40 anti-T serum and which are  not detected in untransformed cells. The additional tumor antigens (T-Ags) fall into two groups: those having a close structural relationship with normal SV40 T-Ags, and those unrelated to large T and small t. The latter are probably nonviral T-Ags (NVT-Ags). The NVT-Ags comprise a family of proteins of molecular weight 50,000-55,000. Fingerprint analysis shows that NVT-Ags have few if any peptides in common with large T or small t, and that they lack the amino terminal tryptic peptide and the peptides unique to small t. NVT-Ags from different species have different fingerprints, but those isolated from different transformants of the same cell line are identical. The size of NVT is unaltered in cells transformed by mutants of SV40 with deletions in the region 0.60-0.55 map units. The mRNA for NVT does not hybridize to SV40 DNA. The other forms of T-Ag isolated from transformed cells fall into three classes: shortened forms of large T (truncated large T); multiple species of T-Ag with molecular weights very similar to, but distinct from, those of normal large T (large T doublets and triplets); and elongated forms of large T (super T). These proteins all contain the normal amino terminus of SV40 T-Ags, and the truncated forms of large T lack peptides from the carboxy terminal half of large T. One species of super T (molecular weight 130,000) contains only those methionine tryptic peptides present in normal large T, although it may contain some peptides in more than one copy.", "contents": "Characterization of different tumor antigens present in cells transformed by simian virus 40. In addition to large T and small t antigens, cells transformed by simian virus 40 (SV40) commonly contain other proteins which specifically immunoprecipitate with SV40 anti-T serum and which are  not detected in untransformed cells. The additional tumor antigens (T-Ags) fall into two groups: those having a close structural relationship with normal SV40 T-Ags, and those unrelated to large T and small t. The latter are probably nonviral T-Ags (NVT-Ags). The NVT-Ags comprise a family of proteins of molecular weight 50,000-55,000. Fingerprint analysis shows that NVT-Ags have few if any peptides in common with large T or small t, and that they lack the amino terminal tryptic peptide and the peptides unique to small t. NVT-Ags from different species have different fingerprints, but those isolated from different transformants of the same cell line are identical. The size of NVT is unaltered in cells transformed by mutants of SV40 with deletions in the region 0.60-0.55 map units. The mRNA for NVT does not hybridize to SV40 DNA. The other forms of T-Ag isolated from transformed cells fall into three classes: shortened forms of large T (truncated large T); multiple species of T-Ag with molecular weights very similar to, but distinct from, those of normal large T (large T doublets and triplets); and elongated forms of large T (super T). These proteins all contain the normal amino terminus of SV40 T-Ags, and the truncated forms of large T lack peptides from the carboxy terminal half of large T. One species of super T (molecular weight 130,000) contains only those methionine tryptic peptides present in normal large T, although it may contain some peptides in more than one copy."}
{"id": "PMID:227605", "title": "Heterogeneity of genetic loci in chickens: analysis of endogenous viral and nonviral genes by cleavage of DNA with restriction endonucleases.", "content": "Restriction endonucleases can be used to define the structure and position of genetic loci for which specific molecular hybridization reagents are available. We have used this approach to compare 18 chicken embryos with respect to several cellular genes; endogenous viral DNA related to the replicative genes of avian sarcoma virus (ASV) or to RAV-O, an endogenous virus of chickens; and sequences related to the transforming (src) gene of ASV. Each cellular gene eas remarkably homogeneous within our test population. We found little or no variation in globin and ovomucoid genes; ovalbumin and transferrin (with one exception) showed variation which is probably allelic in nature. The endogenous viral DNA which has homology with RAV-O was found at several different positions in host DNA and its structure resembled that of proviruses acquired by experimental infection, with sequences from both ends of viral RNA repeated near both ends of viral DNA. Within the population of 18 chickens, one endogenous provirus was always present, whereas the several other proviruses were each found in only a few members of this group. However, screening of additional chickens identified individuals lacking the provirus common to the initial 18 animals surveyed; in at least one embryo no RAV-O-related DNA was detected. These findings suggest that the endogenous RAV-O-related sequences have entered the germ line by relatively recent infection and are still segregating in several contemporary chicken flocks. The sequences in the chicken genome which have homology with the src gene of ASV are invariant from bird to bird and in this sense resemble a cellular gene rather than a viral sequence.", "contents": "Heterogeneity of genetic loci in chickens: analysis of endogenous viral and nonviral genes by cleavage of DNA with restriction endonucleases. Restriction endonucleases can be used to define the structure and position of genetic loci for which specific molecular hybridization reagents are available. We have used this approach to compare 18 chicken embryos with respect to several cellular genes; endogenous viral DNA related to the replicative genes of avian sarcoma virus (ASV) or to RAV-O, an endogenous virus of chickens; and sequences related to the transforming (src) gene of ASV. Each cellular gene eas remarkably homogeneous within our test population. We found little or no variation in globin and ovomucoid genes; ovalbumin and transferrin (with one exception) showed variation which is probably allelic in nature. The endogenous viral DNA which has homology with RAV-O was found at several different positions in host DNA and its structure resembled that of proviruses acquired by experimental infection, with sequences from both ends of viral RNA repeated near both ends of viral DNA. Within the population of 18 chickens, one endogenous provirus was always present, whereas the several other proviruses were each found in only a few members of this group. However, screening of additional chickens identified individuals lacking the provirus common to the initial 18 animals surveyed; in at least one embryo no RAV-O-related DNA was detected. These findings suggest that the endogenous RAV-O-related sequences have entered the germ line by relatively recent infection and are still segregating in several contemporary chicken flocks. The sequences in the chicken genome which have homology with the src gene of ASV are invariant from bird to bird and in this sense resemble a cellular gene rather than a viral sequence."}
{"id": "PMID:227607", "title": "Chicken hematopoietic cells transformed by seven strains of defective avian leukemia viruses display three distinct phenotypes of differentiation.", "content": "Chicken hematopoietic cells transformed in vitro and in vivo by seven strains of replication-defective avian leukemia viruses were assayed for the expression of six erythroid and five myeloid differentiation parameters, including differentiation-specific surface antigens as detected by newly developed antisera. The transformed cells were found to display three distinct phenotypes of differentiation. First, cells transformed by AEV resemble erythroblasts. They express heme, globin, carbonic anhydrase and erythrocyte cell surface antigen at low levels, and histone H5 and erythroblast cell surface antigen at high levels. Second, cells transformed by MC29, CMII, OK10 and MH2 viruses have macrophage-like properties. They strongly express Fc receptors, phagocytic capacity and macrophage cell surface antigen, but only weakly express myeloblast cell surface antigen and are negative for ATPase activity. Third, cells transformed by AMV and E26 viruses resemble myeloblasts in that they weakly express Fc receptors, phagocytic capacity and macrophage cell surface antigen but strongly express myeloblast cell surface antigen and ATPase activity. No difference was found between in vitro- and in vivo-transformed cells in the parameters tested. In light of recent genetic and biochemical evidence, we believe that these phenotypes reflect the action of three new types of viral-transforming genes, designated erb (erythroblast), mac (macrophage) and myb (myeloblast).", "contents": "Chicken hematopoietic cells transformed by seven strains of defective avian leukemia viruses display three distinct phenotypes of differentiation. Chicken hematopoietic cells transformed in vitro and in vivo by seven strains of replication-defective avian leukemia viruses were assayed for the expression of six erythroid and five myeloid differentiation parameters, including differentiation-specific surface antigens as detected by newly developed antisera. The transformed cells were found to display three distinct phenotypes of differentiation. First, cells transformed by AEV resemble erythroblasts. They express heme, globin, carbonic anhydrase and erythrocyte cell surface antigen at low levels, and histone H5 and erythroblast cell surface antigen at high levels. Second, cells transformed by MC29, CMII, OK10 and MH2 viruses have macrophage-like properties. They strongly express Fc receptors, phagocytic capacity and macrophage cell surface antigen, but only weakly express myeloblast cell surface antigen and are negative for ATPase activity. Third, cells transformed by AMV and E26 viruses resemble myeloblasts in that they weakly express Fc receptors, phagocytic capacity and macrophage cell surface antigen but strongly express myeloblast cell surface antigen and ATPase activity. No difference was found between in vitro- and in vivo-transformed cells in the parameters tested. In light of recent genetic and biochemical evidence, we believe that these phenotypes reflect the action of three new types of viral-transforming genes, designated erb (erythroblast), mac (macrophage) and myb (myeloblast)."}
{"id": "PMID:227608", "title": "The asymmetric segregation of parental nucleosomes during chrosome replication.", "content": "SV40 DNA replicated in the presence of cycloheximide was more sensitive to staphylococcal nuclease digestion and had a lower superhelical density than viral DNA replicated in the absence of this drug. These data indicate that fewer nucleosomes are associated with progeny SV40 DNA molecules after DNA replication in the absence of protein synthesis and that these nucleosomes are derived from the parental histones. We designed an experiment to determine whether these parental SV40 nucleosomes segregate to the leading side of the replication form where DNA synthesis is continuous, the lagging side of the fork where DNA synthesis is discontinuous or randomly to both sides of the fork. The results indicate that the parental histones distributed themselves asymmetrically, preferentially (80-90%) segregating with the leading side of both SV40 DNA replication forks during bidirectional replication in the absence of protein synthesis. In the case of SV40, the same parental DNA strands are the templates for the leading side of DNA replication at both forks as well as the templates for the informational or coding strand of early and late viral mRNA synthesis. Based on this correspondence, we designed an experiment to test whether chicken cells growing in culture and replicating their DNA in the absence of protein synthesis segregated their parental histones asymmetrically to the progeny DNA strand that also coded for stable nuclear RNA transcripts. The results of these experiments indicate that, like SV40, parental cellular histones segregate asymmetrically and are preferentially associated with those DNA template strands that code for stable nuclear RNA species detected by hybridization to single-copy DNA.", "contents": "The asymmetric segregation of parental nucleosomes during chrosome replication. SV40 DNA replicated in the presence of cycloheximide was more sensitive to staphylococcal nuclease digestion and had a lower superhelical density than viral DNA replicated in the absence of this drug. These data indicate that fewer nucleosomes are associated with progeny SV40 DNA molecules after DNA replication in the absence of protein synthesis and that these nucleosomes are derived from the parental histones. We designed an experiment to determine whether these parental SV40 nucleosomes segregate to the leading side of the replication form where DNA synthesis is continuous, the lagging side of the fork where DNA synthesis is discontinuous or randomly to both sides of the fork. The results indicate that the parental histones distributed themselves asymmetrically, preferentially (80-90%) segregating with the leading side of both SV40 DNA replication forks during bidirectional replication in the absence of protein synthesis. In the case of SV40, the same parental DNA strands are the templates for the leading side of DNA replication at both forks as well as the templates for the informational or coding strand of early and late viral mRNA synthesis. Based on this correspondence, we designed an experiment to test whether chicken cells growing in culture and replicating their DNA in the absence of protein synthesis segregated their parental histones asymmetrically to the progeny DNA strand that also coded for stable nuclear RNA transcripts. The results of these experiments indicate that, like SV40, parental cellular histones segregate asymmetrically and are preferentially associated with those DNA template strands that code for stable nuclear RNA species detected by hybridization to single-copy DNA."}
{"id": "PMID:227609", "title": "Transcription maps of mtDNAs of two strains of saccharomyces: transcription of strain-specific insertions; Complex RNA maturation and splicing.", "content": "We have developed a two-dimensional method for simultaneously mapping on the yeast mtDNA genome all the transcripts representing more than 0.01% of mtRNA. In two yeast strains, Saccharomyces carlsbergensis NCYC-74 and Saccharomyces cerevisiae KL14-4A, about 25 discrete transcripts were found apart from tRNAs. The mtDNAs of these strains differ by the absence (NCYC-74) or presence (KL 14-4A) of various large insertions located within genetically active regions. The transcripts can all be related to known loci on the genetic map. In nearly all cases the RNAs are much longer than required to specify the known protein product of the locus concerned. The organization of the transcripts is similar in the two strains except at the positions of the large insertions (500-3300 bp) in the oxi-3 and cob loci. The sequences of these insertions are present in RNA species larger than 25S, but are absent from smaller transcripts of the same regions. This is probably due to splicing, since the coding sequences for most of these smaller transcripts are noncontiguous. The smaller transcripts of other loci also seem to arise from processing of larger RNA species. The oxi-3 locus, containing the structural gene for cytochrome c oxidase subunit l, is transcribed in a very complex fashion that suggests differential splicing into partially overlapping transcripts. This may indicate that oxi-3 has additional genetic functions, including possible control of the biosynthesis of cytochrome c oxidase holoenzyme or its assembly into the mitochondrial inner membrane. As in the case of the eucaryote nucleus, the regulation of mitochondrial gene expression seems to occur more at the level of RNA processing than has been recognized thus far.", "contents": "Transcription maps of mtDNAs of two strains of saccharomyces: transcription of strain-specific insertions; Complex RNA maturation and splicing. We have developed a two-dimensional method for simultaneously mapping on the yeast mtDNA genome all the transcripts representing more than 0.01% of mtRNA. In two yeast strains, Saccharomyces carlsbergensis NCYC-74 and Saccharomyces cerevisiae KL14-4A, about 25 discrete transcripts were found apart from tRNAs. The mtDNAs of these strains differ by the absence (NCYC-74) or presence (KL 14-4A) of various large insertions located within genetically active regions. The transcripts can all be related to known loci on the genetic map. In nearly all cases the RNAs are much longer than required to specify the known protein product of the locus concerned. The organization of the transcripts is similar in the two strains except at the positions of the large insertions (500-3300 bp) in the oxi-3 and cob loci. The sequences of these insertions are present in RNA species larger than 25S, but are absent from smaller transcripts of the same regions. This is probably due to splicing, since the coding sequences for most of these smaller transcripts are noncontiguous. The smaller transcripts of other loci also seem to arise from processing of larger RNA species. The oxi-3 locus, containing the structural gene for cytochrome c oxidase subunit l, is transcribed in a very complex fashion that suggests differential splicing into partially overlapping transcripts. This may indicate that oxi-3 has additional genetic functions, including possible control of the biosynthesis of cytochrome c oxidase holoenzyme or its assembly into the mitochondrial inner membrane. As in the case of the eucaryote nucleus, the regulation of mitochondrial gene expression seems to occur more at the level of RNA processing than has been recognized thus far."}
{"id": "PMID:227610", "title": "Messenger RNA for the Ad2 DNA binding protein: DNA sequences encoding the first leader and heterogenity at the mRNA 5' end.", "content": "During the early stage of Ad2 infection of human cells, RNA is transcribed from five separate transcription units. Early region II encodes the mRNA for a 72K single-stranded DNA binding protein (DBP) which functions in DNA replication. This report describes the structure of the first leader of the DBP mRNA and the flanking sequences in the DNA. The leader, labeled in vivo with 32P, was isolated by DNA filter hybridization to the viral restriction fragment Eco RI F, and its RNAase T1 and RNAase A oligonucleotides were analyzed by RNA fingerprinting techniques. Comparison of this RNA sequence information with the DNA sequence of Eco RI F has located a 68 nucleotide region of the Hae III C subfragment at coordinate 75.1 that encodes the leader. This position is near the coordinate to which nascent chain analysis and ultraviolet transcription mapping have mapped an RNA initiation site, or promoter, for the DBP mRNA. The DNA sequence that overlaps the leader on the 3' side contains a donor sequence for splicing this leader to a second downstream leader. The splicing sequence shows a seven base homology with the comparable structure of the Ad2 major late leader, and a mouse globin mRNA splicing sequence. The DNA sequence upstream from the cap, the region oof the potential promoter site does not, however, contain a \"TA-TAAA\"-type homology of the sort noted by D. Hogness, M. Goldberg and R. Lifton (personal communication) for many cellular transcription units, and by other investigations for the Ad2 major late transcription unit. Also, the leader is found with two distinct capped 5' termini, 7meGpppA and 7meGpppG, which are encoded at adjacent positions in the DNA and thus are from mRNAs which are staggered by one nucleotide in length at the 5' end. The staggering at the 5' terminus and the lack of the upstream homolgy distinguish the DBP mRNA from many viral and cellular messenger. In both these respects, however, the DBP mRNA resembles the late messengers of SV40 and polyoma viruses. In this paper, we discuss the implications of these findings for the mechanism of specifying mRNA 5' ends.", "contents": "Messenger RNA for the Ad2 DNA binding protein: DNA sequences encoding the first leader and heterogenity at the mRNA 5' end. During the early stage of Ad2 infection of human cells, RNA is transcribed from five separate transcription units. Early region II encodes the mRNA for a 72K single-stranded DNA binding protein (DBP) which functions in DNA replication. This report describes the structure of the first leader of the DBP mRNA and the flanking sequences in the DNA. The leader, labeled in vivo with 32P, was isolated by DNA filter hybridization to the viral restriction fragment Eco RI F, and its RNAase T1 and RNAase A oligonucleotides were analyzed by RNA fingerprinting techniques. Comparison of this RNA sequence information with the DNA sequence of Eco RI F has located a 68 nucleotide region of the Hae III C subfragment at coordinate 75.1 that encodes the leader. This position is near the coordinate to which nascent chain analysis and ultraviolet transcription mapping have mapped an RNA initiation site, or promoter, for the DBP mRNA. The DNA sequence that overlaps the leader on the 3' side contains a donor sequence for splicing this leader to a second downstream leader. The splicing sequence shows a seven base homology with the comparable structure of the Ad2 major late leader, and a mouse globin mRNA splicing sequence. The DNA sequence upstream from the cap, the region oof the potential promoter site does not, however, contain a \"TA-TAAA\"-type homology of the sort noted by D. Hogness, M. Goldberg and R. Lifton (personal communication) for many cellular transcription units, and by other investigations for the Ad2 major late transcription unit. Also, the leader is found with two distinct capped 5' termini, 7meGpppA and 7meGpppG, which are encoded at adjacent positions in the DNA and thus are from mRNAs which are staggered by one nucleotide in length at the 5' end. The staggering at the 5' terminus and the lack of the upstream homolgy distinguish the DBP mRNA from many viral and cellular messenger. In both these respects, however, the DBP mRNA resembles the late messengers of SV40 and polyoma viruses. In this paper, we discuss the implications of these findings for the mechanism of specifying mRNA 5' ends."}
{"id": "PMID:227612", "title": "[\"Giant\" oncocytic renal adenomas].", "content": "Postmortem and bioptic material from the 1953-1976 period included 7 cases of oncocytic renal adenoma larger than 5 cm including 3 larger than 10 cm. Macroscopic characteristics included red-brownish coloration and extensive foci of central hyalinosis. Microscopy showed them as being made up of cells resembling oncocytes with relatively active nuclei with solid, occasionally focus-like tubular structure. In spite of the large size and, in some rarer cases, focal nuclear atypia all of the tumours appeared to behave in a benign way. The causes of their increased frequency in the past decade remain to be clarified yet.", "contents": "[\"Giant\" oncocytic renal adenomas]. Postmortem and bioptic material from the 1953-1976 period included 7 cases of oncocytic renal adenoma larger than 5 cm including 3 larger than 10 cm. Macroscopic characteristics included red-brownish coloration and extensive foci of central hyalinosis. Microscopy showed them as being made up of cells resembling oncocytes with relatively active nuclei with solid, occasionally focus-like tubular structure. In spite of the large size and, in some rarer cases, focal nuclear atypia all of the tumours appeared to behave in a benign way. The causes of their increased frequency in the past decade remain to be clarified yet."}
{"id": "PMID:227613", "title": "Mechanisms of inhibition of active transport ATPases by mercurials.", "content": "Inhibition by methylmercury and mercuric chloride of Mg,Ca ATPase and Na,K ATPase activities in human erythrocyte ghosts was correlated with the binding capacity of ghosts for the mercurial. Full inhibition was always reached below saturation of binding capacity, and half-inhibition at levels as low as 10% saturation. Under such conditions, concentrations of free inhibitor were negligibly low, and existing mathematical models of inhibition were not applicable. New inhibitor partition equations were introduced to model the mechanisms of action of mercurials. Up to 7 methylmercury groups were calculated to bind to one Na,K ATPase molecule at non-inhibitory sites, while only one reacted with the inhibitory site. Mg,Ca ATPase showed simple one-hit inhibition (one mercurial per enzyme); further washing of ghosts, however, unmasked a second binding site (cooperative two-hit inhibition). Affinities of mercurials to sites of inhibition were calculated relative to other ligands in erythrocyte membranes: the ratios ranged from 3 : 1 to 50 : 1. The results demonstrated the use of binding capacity assays and inhibitor partition equations to measure and compare the susceptibilities of membrane-bound enzymes to poisoning by mercurials.", "contents": "Mechanisms of inhibition of active transport ATPases by mercurials. Inhibition by methylmercury and mercuric chloride of Mg,Ca ATPase and Na,K ATPase activities in human erythrocyte ghosts was correlated with the binding capacity of ghosts for the mercurial. Full inhibition was always reached below saturation of binding capacity, and half-inhibition at levels as low as 10% saturation. Under such conditions, concentrations of free inhibitor were negligibly low, and existing mathematical models of inhibition were not applicable. New inhibitor partition equations were introduced to model the mechanisms of action of mercurials. Up to 7 methylmercury groups were calculated to bind to one Na,K ATPase molecule at non-inhibitory sites, while only one reacted with the inhibitory site. Mg,Ca ATPase showed simple one-hit inhibition (one mercurial per enzyme); further washing of ghosts, however, unmasked a second binding site (cooperative two-hit inhibition). Affinities of mercurials to sites of inhibition were calculated relative to other ligands in erythrocyte membranes: the ratios ranged from 3 : 1 to 50 : 1. The results demonstrated the use of binding capacity assays and inhibitor partition equations to measure and compare the susceptibilities of membrane-bound enzymes to poisoning by mercurials."}
{"id": "PMID:227614", "title": "Benzo[a]pyrene--serum : albumin/cysteine interactions: fluorescence and electron spin resonance studies.", "content": "The complex between bovine serum albumin (BSA) and benzo[a]pyrene (BaP) exhibits three different types of fluorescence. The visible fluorescence at 407, 431 and 458 nm is modified by the formation of both hydroxy-BaP derivatives and BaP products strongly bound to the protein. The ultraviolet fluorescence I is characterized by a triple-peaked structural fluorescence with maxima at 340, 357 and 378 nm. Upon addition of mercaptoethanol, this ultraviolet fluorescence decreases. The ultraviolet fluorescence II appears at 380 nm and corresponds to that of pyrene-like products. When irradiated with ultraviolet (365 nm) light, both the ultraviolet fluorescence I and the visible fluorescence decreases. In the interactionsof BaP with BSA, a new radical has also been found in addition to the known 6-oxo-BaP radical. The lyophilized BSA-BaP complex exhibits two broad ESR bands, one of which increases in lipid-free BSA. In the concentrated aqueous solution of the BSA-BaP complex, the ESR signal is converted to a six-line spectrum. The benzene extract, which removes non-covalently bound BaP products, shows an ESR signal similar to that in aqueous solution except for the absence of two lower g-valued lines. When irradiated with ultraviolet (365 nm) light the signal intensity of the new radical species decreases, while that of 6-oxo-BaP increases. Upon addition of of mercaptoethanol, the signal of the new radical also diminishes and is replaced by a single narrow signal. Ths mixture of BaP and cysteine kept at room temperature for one day in the dark produces both a six-line ESR spectrum and a broad ultraviolet fluorescence at 330 nm, which gradually decay in about one week. When BaP and cysteine are mixed at 65 degrees C for several hours, little ultraviolet fluorescence and ESR signal are detected. The results indicate the formation of a BaP radical as an intermediate in the interaction of BaP with BSA and cysteine in the presence of oxygen and suggest the involvement of SH-groups in this interaction.", "contents": "Benzo[a]pyrene--serum : albumin/cysteine interactions: fluorescence and electron spin resonance studies. The complex between bovine serum albumin (BSA) and benzo[a]pyrene (BaP) exhibits three different types of fluorescence. The visible fluorescence at 407, 431 and 458 nm is modified by the formation of both hydroxy-BaP derivatives and BaP products strongly bound to the protein. The ultraviolet fluorescence I is characterized by a triple-peaked structural fluorescence with maxima at 340, 357 and 378 nm. Upon addition of mercaptoethanol, this ultraviolet fluorescence decreases. The ultraviolet fluorescence II appears at 380 nm and corresponds to that of pyrene-like products. When irradiated with ultraviolet (365 nm) light, both the ultraviolet fluorescence I and the visible fluorescence decreases. In the interactionsof BaP with BSA, a new radical has also been found in addition to the known 6-oxo-BaP radical. The lyophilized BSA-BaP complex exhibits two broad ESR bands, one of which increases in lipid-free BSA. In the concentrated aqueous solution of the BSA-BaP complex, the ESR signal is converted to a six-line spectrum. The benzene extract, which removes non-covalently bound BaP products, shows an ESR signal similar to that in aqueous solution except for the absence of two lower g-valued lines. When irradiated with ultraviolet (365 nm) light the signal intensity of the new radical species decreases, while that of 6-oxo-BaP increases. Upon addition of of mercaptoethanol, the signal of the new radical also diminishes and is replaced by a single narrow signal. Ths mixture of BaP and cysteine kept at room temperature for one day in the dark produces both a six-line ESR spectrum and a broad ultraviolet fluorescence at 330 nm, which gradually decay in about one week. When BaP and cysteine are mixed at 65 degrees C for several hours, little ultraviolet fluorescence and ESR signal are detected. The results indicate the formation of a BaP radical as an intermediate in the interaction of BaP with BSA and cysteine in the presence of oxygen and suggest the involvement of SH-groups in this interaction."}
{"id": "PMID:227615", "title": "Binding of nitrosamines to cytochrome P-450 of liver microsomes.", "content": "The interactions of 5 carcinogenic and 1 non-carcinogenic nitrosamines with hepatic microsomal cytochrome (cyt.) P-450 were investigated, using both optical difference and electron paramagnetic resonance (EPR) spectroscopic methods. Liver microsomes from phenobarbital (PB)-pretreated mice and 3-methylcholanthrene (3-MC)-pretreated rats were used, in order to have an increased specific content of cyt. P-450 and cyt. P-448 respectively. The optical and EPR spectral data obtained in the oxidised state suggest that nitrosamines are able to bind both as substrates and as ligands to the hemoprotein cyt. P-450, depending on the concentration of nitrosamine, its chemical identity and the cytochrome species present. After reduction with dithionite or NADPH in the optical difference spectrum a Soret band developed between 444 and 453 nm to an extent, which is dependent on the particular nitrosamine present. This initial nitrosamine-induced spectrum might represent a ferrous nitric oxide (NO)-cyt. P-450 complex. It appears unstable and is converted kinetically into a spectrum lacking a Soret band, but with a predominant absorbance minimum at about 425 nm. A visible band is located at 585 nm. In the EPR spectrum a sharp 3-line signal around g = 2.01 appears concomitantly. Both spectral parameters are typical of a NO-cyt. P-420 complex. These results, in conjunction with metabolic studies, indicate that nitrosamines are denitrosated by a reductive process in which cyt. P-450 appears to be involved. The resulting NO-cyt. P-450 complex denatures to a NO-cyt. P-420 complex when the dioxygen level is not sufficiently high to complete successfully.", "contents": "Binding of nitrosamines to cytochrome P-450 of liver microsomes. The interactions of 5 carcinogenic and 1 non-carcinogenic nitrosamines with hepatic microsomal cytochrome (cyt.) P-450 were investigated, using both optical difference and electron paramagnetic resonance (EPR) spectroscopic methods. Liver microsomes from phenobarbital (PB)-pretreated mice and 3-methylcholanthrene (3-MC)-pretreated rats were used, in order to have an increased specific content of cyt. P-450 and cyt. P-448 respectively. The optical and EPR spectral data obtained in the oxidised state suggest that nitrosamines are able to bind both as substrates and as ligands to the hemoprotein cyt. P-450, depending on the concentration of nitrosamine, its chemical identity and the cytochrome species present. After reduction with dithionite or NADPH in the optical difference spectrum a Soret band developed between 444 and 453 nm to an extent, which is dependent on the particular nitrosamine present. This initial nitrosamine-induced spectrum might represent a ferrous nitric oxide (NO)-cyt. P-450 complex. It appears unstable and is converted kinetically into a spectrum lacking a Soret band, but with a predominant absorbance minimum at about 425 nm. A visible band is located at 585 nm. In the EPR spectrum a sharp 3-line signal around g = 2.01 appears concomitantly. Both spectral parameters are typical of a NO-cyt. P-420 complex. These results, in conjunction with metabolic studies, indicate that nitrosamines are denitrosated by a reductive process in which cyt. P-450 appears to be involved. The resulting NO-cyt. P-450 complex denatures to a NO-cyt. P-420 complex when the dioxygen level is not sufficiently high to complete successfully."}
{"id": "PMID:227618", "title": "Effect of moderate physical exercise on serum lipoproteins. A controlled clinical trial with special reference to serum high-density lipoproteins.", "content": "A controlled trial is reported on the effects of mild-to-moderate physical activity on serum lipoproteins. After two baseline examinations 100 asymptomatic middle-aged men were randomly assigned to exercise and control groups. The exercise group participated in a 4-month exercise program that consisted of 3-4 weekly sessions. The control group was advised to maintain their previous exercise habits. The success of the program was corroborated by the increase in VO2 in the training group, but not in the control group. Serum triglycerides decreased from 1.54 +/- 0.10 to 1.27 +/- 0.08 mmol/1 (p less than 0.001) and high-density lipoprotein (HDL) cholesterol increased from 1.27 +/- 0.04 to 1.41 +/- 0.04 mmol/1 (p less than 0.01) in the exercise group during the trial. No change was seen in the control group. As the concentration of apolipoprotein AI stayed constant in both groups, the ratio HDL cholesterol/apolipoprotein AI increased only in the exercise group. The level of low-density lipoprotein (LDL) cholesterol and apolipoprotein AII decreased in both groups during the trial. The alterations in serum triglycerides and HDL cholesterol in the exercise group were not dependent on weight reduction; similar changes were also seen in subjects with constant body weight during the intervention.", "contents": "Effect of moderate physical exercise on serum lipoproteins. A controlled clinical trial with special reference to serum high-density lipoproteins. A controlled trial is reported on the effects of mild-to-moderate physical activity on serum lipoproteins. After two baseline examinations 100 asymptomatic middle-aged men were randomly assigned to exercise and control groups. The exercise group participated in a 4-month exercise program that consisted of 3-4 weekly sessions. The control group was advised to maintain their previous exercise habits. The success of the program was corroborated by the increase in VO2 in the training group, but not in the control group. Serum triglycerides decreased from 1.54 +/- 0.10 to 1.27 +/- 0.08 mmol/1 (p less than 0.001) and high-density lipoprotein (HDL) cholesterol increased from 1.27 +/- 0.04 to 1.41 +/- 0.04 mmol/1 (p less than 0.01) in the exercise group during the trial. No change was seen in the control group. As the concentration of apolipoprotein AI stayed constant in both groups, the ratio HDL cholesterol/apolipoprotein AI increased only in the exercise group. The level of low-density lipoprotein (LDL) cholesterol and apolipoprotein AII decreased in both groups during the trial. The alterations in serum triglycerides and HDL cholesterol in the exercise group were not dependent on weight reduction; similar changes were also seen in subjects with constant body weight during the intervention."}
{"id": "PMID:227619", "title": "Survival of the ischemic brain: a progress report.", "content": "The number of patients with cerebral infarctions increases as the population ages, despite campaigns against hypertension, the greatest risk factor. Cerebral ischemia initiates events that are presumed to defer the stage of irreversible injury. These events cause an increase of perfusion around the central ischemic zone and trigger the Bohr effect, both of which preserve tissue viability. Almost simultaneously, mitochondrial function fails, resulting in insufficient energy for the enzyme systems to control Na and K ion equilibrium. At the same time, protein synthesis slows and cellular respiratory enzymes decrease their activity, initiating an irreversible state of tissue change. Tissue fatty acids increase as a result of dissolution of cell membrane lipoprotein structure. Barbiturates reduce the extent of experimental infarction. Resperine and aminophylline are also effective, but there are no corroborative clinical trials. That ischemic brain damage may be the result of toxic substances in the ischemic tissue represents a new concept.", "contents": "Survival of the ischemic brain: a progress report. The number of patients with cerebral infarctions increases as the population ages, despite campaigns against hypertension, the greatest risk factor. Cerebral ischemia initiates events that are presumed to defer the stage of irreversible injury. These events cause an increase of perfusion around the central ischemic zone and trigger the Bohr effect, both of which preserve tissue viability. Almost simultaneously, mitochondrial function fails, resulting in insufficient energy for the enzyme systems to control Na and K ion equilibrium. At the same time, protein synthesis slows and cellular respiratory enzymes decrease their activity, initiating an irreversible state of tissue change. Tissue fatty acids increase as a result of dissolution of cell membrane lipoprotein structure. Barbiturates reduce the extent of experimental infarction. Resperine and aminophylline are also effective, but there are no corroborative clinical trials. That ischemic brain damage may be the result of toxic substances in the ischemic tissue represents a new concept."}
{"id": "PMID:227620", "title": "Electrophoretic separation of high-density lipoprotein choelsterol evaluated and compared with the modified lipid research clinic procedure.", "content": "We evaluated a new agarose-gel-electrophoretic procedure (Corning) (I) for separating and quantitating of high-density lipoprotein cholesterol (HDLC), comparing it with the modified Lipid Research Clinics (LRC) procedure (heparin 183 kilounits/L, MnCl2 92 mmol/L) (II). Method I was insensitive to an HDLC concentration of 50 mg/L, but gave a linear dose-response curve between 130 and 1200 mg/L. Method II is sensitive to 50 mg/L and linear from 50--1200 mg/L. The within-plate CV for the Corning method varied from 26.2% for an HDLC of 168 mg/L to 6.8% for 580 mg/L. Within-day between-plate CV for the Corning method ranged from 22.1% at 155 mg/L to 8.0% at 651 mg/L, compared to 3.0 and 0.8% for the modified LRC procedure. Between-day CV for method I was 20, 12.6, 4.3, and 3.5% for HDLC concentrations of 175, 435, 542, and 678 mg/L, respectively; for method II it was 14, 5, 3.5, and 2.6%, respectively. Analysis of HDLC in 100 patients by both procedures showed mean HDLC values to be significantly lower (mean + SD, 27.8 +/- 1.7 mg/L; p less than 0.001) by method I. In 46 patients with HDLC less than 450 mg/L, this difference was accentuated (mean + SD = 40.5 +/- 2.6 mg/L) and clinically significant. Electrophoretic methods offer a promising further alternative method for HDLC separation and quantitation, but the negative bias, present limited sensitivity, and lack of precision at less than 450 mg/L indicate that they are not yet optimal for routine clinical use for patients with values less than 450 mg/L.", "contents": "Electrophoretic separation of high-density lipoprotein choelsterol evaluated and compared with the modified lipid research clinic procedure. We evaluated a new agarose-gel-electrophoretic procedure (Corning) (I) for separating and quantitating of high-density lipoprotein cholesterol (HDLC), comparing it with the modified Lipid Research Clinics (LRC) procedure (heparin 183 kilounits/L, MnCl2 92 mmol/L) (II). Method I was insensitive to an HDLC concentration of 50 mg/L, but gave a linear dose-response curve between 130 and 1200 mg/L. Method II is sensitive to 50 mg/L and linear from 50--1200 mg/L. The within-plate CV for the Corning method varied from 26.2% for an HDLC of 168 mg/L to 6.8% for 580 mg/L. Within-day between-plate CV for the Corning method ranged from 22.1% at 155 mg/L to 8.0% at 651 mg/L, compared to 3.0 and 0.8% for the modified LRC procedure. Between-day CV for method I was 20, 12.6, 4.3, and 3.5% for HDLC concentrations of 175, 435, 542, and 678 mg/L, respectively; for method II it was 14, 5, 3.5, and 2.6%, respectively. Analysis of HDLC in 100 patients by both procedures showed mean HDLC values to be significantly lower (mean + SD, 27.8 +/- 1.7 mg/L; p less than 0.001) by method I. In 46 patients with HDLC less than 450 mg/L, this difference was accentuated (mean + SD = 40.5 +/- 2.6 mg/L) and clinically significant. Electrophoretic methods offer a promising further alternative method for HDLC separation and quantitation, but the negative bias, present limited sensitivity, and lack of precision at less than 450 mg/L indicate that they are not yet optimal for routine clinical use for patients with values less than 450 mg/L."}
{"id": "PMID:227621", "title": "Quantitative determination of high-density lipoprotein cholesterol by agarose gel electrophoresis.", "content": "We have developed a procedure for the determination of high-density lipoprotein cholesterol by agarose gel electrophoresis. Only 2 micro L of sample was applied to the gel. After electrophoresis at 90 V for 35 min, an enzymatic cholesterol reagent was applied. After a 30-min incubation, the high-density lipoprotein cholesterol was quantified by densitometry. Precision for this measurment approaches that reported for the heparin-manganese/Abell-Kendall method (Clin. Chem, 25: 596--609, 1979). We evaluated accuracy by comparing high-density lipoprotein cholesterol concentration measured by electrophoresis to that determined in the Framingham Heart Study procedure (J. Biol. Chem. 195: 357, 1952). The resulting correlation was excellent. By the paired Student's t-test, there was no significant difference between the two methods. The proposed method gives a linear standard curve when the concentration of total cholesterol is between 1.0 and 3.5 g/L. By accurate quantitation of high-density lipoprotein cholesterol, agarose gel electrophoresis can aid in assessment of coronary heart disease risk for a large segment of the population.", "contents": "Quantitative determination of high-density lipoprotein cholesterol by agarose gel electrophoresis. We have developed a procedure for the determination of high-density lipoprotein cholesterol by agarose gel electrophoresis. Only 2 micro L of sample was applied to the gel. After electrophoresis at 90 V for 35 min, an enzymatic cholesterol reagent was applied. After a 30-min incubation, the high-density lipoprotein cholesterol was quantified by densitometry. Precision for this measurment approaches that reported for the heparin-manganese/Abell-Kendall method (Clin. Chem, 25: 596--609, 1979). We evaluated accuracy by comparing high-density lipoprotein cholesterol concentration measured by electrophoresis to that determined in the Framingham Heart Study procedure (J. Biol. Chem. 195: 357, 1952). The resulting correlation was excellent. By the paired Student's t-test, there was no significant difference between the two methods. The proposed method gives a linear standard curve when the concentration of total cholesterol is between 1.0 and 3.5 g/L. By accurate quantitation of high-density lipoprotein cholesterol, agarose gel electrophoresis can aid in assessment of coronary heart disease risk for a large segment of the population."}
{"id": "PMID:227622", "title": "High concentrations of free kinins and kinin system components in abdominal transudate of a patient with nephrotic syndrome.", "content": "High levels of bradykinin (60--80 ng/ml) were found in abdominal transudate from a patient with nephrotic syndrome caused by chronic glomerulonephritis. The abdominal transudate contained neutral kininogenase and its precursor, identified with plasma kallikrein and prekallikrein, respectively, as well as both forms of kininogen, the low-molecular-weight form predominating. The abdominal transudate was characterized also by very low kininase activity and low levels of alpha 1-antitrypsin (0.46 g/l) and alpha 2-macroglobulin. Large amounts of very low density lipoproteins were present in the transudate. Despite the difference in total protein content between the abdominal transudate and the patient's serum (4.3 g/l and 48 g/l, respectively) their protein fraction composition was similar. The data obtained suggest that bradykinin is important in maintenance of long-lasting blood vessel hyperpermeability, which, in turn, is a driving force in the pathogenesis of refractory nephrotic edema.", "contents": "High concentrations of free kinins and kinin system components in abdominal transudate of a patient with nephrotic syndrome. High levels of bradykinin (60--80 ng/ml) were found in abdominal transudate from a patient with nephrotic syndrome caused by chronic glomerulonephritis. The abdominal transudate contained neutral kininogenase and its precursor, identified with plasma kallikrein and prekallikrein, respectively, as well as both forms of kininogen, the low-molecular-weight form predominating. The abdominal transudate was characterized also by very low kininase activity and low levels of alpha 1-antitrypsin (0.46 g/l) and alpha 2-macroglobulin. Large amounts of very low density lipoproteins were present in the transudate. Despite the difference in total protein content between the abdominal transudate and the patient's serum (4.3 g/l and 48 g/l, respectively) their protein fraction composition was similar. The data obtained suggest that bradykinin is important in maintenance of long-lasting blood vessel hyperpermeability, which, in turn, is a driving force in the pathogenesis of refractory nephrotic edema."}
{"id": "PMID:227623", "title": "[Spectrophotometric assay of angiotensin I-converting enzyme (author's transl)].", "content": "The method of chemical assay of angiotensin I-converting enzyme described is a modification of the previously published spectrophotometric assay based on quantitation of hippuric acid released from hippuryl-L-histidyl-L-leucine. The new procedure involves extraction of hippuric acid with ethylacetate, evaporation to dryness of the extract, solubilization of the residue with 1 mol/l NaCl and purification with petroleum ether before measurements of the absorbance at 228 nm of the aqueous phase. Under these conditions, hippuric acid insoluble in petroleum ether remains in the aqueous phase, whereas other A228-absorbing materials, readily soluble in the ether and able to interfere with the assay, are eliminated.", "contents": "[Spectrophotometric assay of angiotensin I-converting enzyme (author's transl)]. The method of chemical assay of angiotensin I-converting enzyme described is a modification of the previously published spectrophotometric assay based on quantitation of hippuric acid released from hippuryl-L-histidyl-L-leucine. The new procedure involves extraction of hippuric acid with ethylacetate, evaporation to dryness of the extract, solubilization of the residue with 1 mol/l NaCl and purification with petroleum ether before measurements of the absorbance at 228 nm of the aqueous phase. Under these conditions, hippuric acid insoluble in petroleum ether remains in the aqueous phase, whereas other A228-absorbing materials, readily soluble in the ether and able to interfere with the assay, are eliminated."}
{"id": "PMID:227624", "title": "[Quantitative analysis of lipoproteins in hyperlipoproteinemias of type IIa, IIb and IV (author's transl)].", "content": "Cholesterol and triglyceride content of serum lipoprotein fractions isolated by ultracentrifugation have been studied in 33 healthy subjects and in 56 subjects affected by hyperlipoproteinemia of type IIa, IIb and IV. Patients with atherosclerotic disease were characterized by a general decrease of HDL cholesterol and by a negative correlation between HDL cholesterol and VLDL triglycerides; patients with type IIb and IV showed an increase of LDL lipoproteins. The increase of triglycerides in type IIb and IV was caused by elevation of VLDL triglycerides or LDL triglycerides, and the increase of cholesterol in type IIb is sometimes caused by elevation of VLDL cholesterol. It is evident that several subtypes exist within Fredrickson's classification. Patients with cerebral arterial disease when compared with patients affected by non-ischaemic disease, showed a negative and significant correlation between HDL cholesterol and total cholesterol.", "contents": "[Quantitative analysis of lipoproteins in hyperlipoproteinemias of type IIa, IIb and IV (author's transl)]. Cholesterol and triglyceride content of serum lipoprotein fractions isolated by ultracentrifugation have been studied in 33 healthy subjects and in 56 subjects affected by hyperlipoproteinemia of type IIa, IIb and IV. Patients with atherosclerotic disease were characterized by a general decrease of HDL cholesterol and by a negative correlation between HDL cholesterol and VLDL triglycerides; patients with type IIb and IV showed an increase of LDL lipoproteins. The increase of triglycerides in type IIb and IV was caused by elevation of VLDL triglycerides or LDL triglycerides, and the increase of cholesterol in type IIb is sometimes caused by elevation of VLDL cholesterol. It is evident that several subtypes exist within Fredrickson's classification. Patients with cerebral arterial disease when compared with patients affected by non-ischaemic disease, showed a negative and significant correlation between HDL cholesterol and total cholesterol."}
{"id": "PMID:227625", "title": "Influence of urine on \"in vitro\" crystallization rate of calcium oxalate: determination of inhibitory activity by a [14C]oxalate technique.", "content": "A simple radiochemical method is proposed for the in vitro assay of the inhibitory activity of urine with respect to calcium oxalate crystal growth using [14C]oxalate as a tracer. The method shows an improved sensitivity over existing methods and indicates that citrate, pyrophosphate and chondroitin sulphate are active inhibitors of calcium oxalate crystal growth down to concentrations of 10(-5), 10(-7) and 10(-10) mol/l respectively. The inhibitory activity in the urines of 12 recurrent calcium stone-formers was significantly lower than in the urines of matched control subjects (P less than 0.01), confirming the clinical usefulness of the test.", "contents": "Influence of urine on \"in vitro\" crystallization rate of calcium oxalate: determination of inhibitory activity by a [14C]oxalate technique. A simple radiochemical method is proposed for the in vitro assay of the inhibitory activity of urine with respect to calcium oxalate crystal growth using [14C]oxalate as a tracer. The method shows an improved sensitivity over existing methods and indicates that citrate, pyrophosphate and chondroitin sulphate are active inhibitors of calcium oxalate crystal growth down to concentrations of 10(-5), 10(-7) and 10(-10) mol/l respectively. The inhibitory activity in the urines of 12 recurrent calcium stone-formers was significantly lower than in the urines of matched control subjects (P less than 0.01), confirming the clinical usefulness of the test."}
{"id": "PMID:227626", "title": "An improved method for the determination of acetaldehyde in human blood with minimal ethanol interference.", "content": "A sensitive method for the determination of acetaldehyde in human blood is described which involves the derivatization of acetaldehyde with semicarbazide followed by head-space gas chromatographic analysis of acetaldehyde in plasma samples after acid hydrolysis of the semicarbazone derivative. Quantitative recovery of acetaldehyde from human blood was achieved and interference from ethanol, a major problem associated with earlier methods, was negligible.", "contents": "An improved method for the determination of acetaldehyde in human blood with minimal ethanol interference. A sensitive method for the determination of acetaldehyde in human blood is described which involves the derivatization of acetaldehyde with semicarbazide followed by head-space gas chromatographic analysis of acetaldehyde in plasma samples after acid hydrolysis of the semicarbazone derivative. Quantitative recovery of acetaldehyde from human blood was achieved and interference from ethanol, a major problem associated with earlier methods, was negligible."}
{"id": "PMID:227627", "title": "The specific release of sialytransferase activity by human hepatoma cell lines.", "content": "Sialyltransferase (EC 2.4.99.1) is released in large amounts by two hepatoma cell lines (SK-H-MA and CLH) established from patients with hepatocellular carcinoma (hepatoma). This release requires protein synthesis and glycoprotein synthesis, but not cell division. In contrast, sialyltransferase is released in minimal amounts by a cell line derived from normal human liver (Chang). The hepatoma cells also contain more surface and cellular sialyltransferase activity than Change cells. Hepatoma sialyltransferase has properties similar to other sialyltransferases. Using a calibrated Sephadex G-200 column, it is resolved into two forms with molecular weights of 65 000 and 80 000.", "contents": "The specific release of sialytransferase activity by human hepatoma cell lines. Sialyltransferase (EC 2.4.99.1) is released in large amounts by two hepatoma cell lines (SK-H-MA and CLH) established from patients with hepatocellular carcinoma (hepatoma). This release requires protein synthesis and glycoprotein synthesis, but not cell division. In contrast, sialyltransferase is released in minimal amounts by a cell line derived from normal human liver (Chang). The hepatoma cells also contain more surface and cellular sialyltransferase activity than Change cells. Hepatoma sialyltransferase has properties similar to other sialyltransferases. Using a calibrated Sephadex G-200 column, it is resolved into two forms with molecular weights of 65 000 and 80 000."}
{"id": "PMID:227628", "title": "Response of plasma lipoproteins and acute phase proteins to myocardial infarction.", "content": "Plasma concentrations of lipoprotein-lipids, apolipoprotein B (apoB) and of seven other proteins have been estimated serially in 27 patients up to three months following myocardial infarction. Results were compared with those from age- and sex-matched control subjects. At three months the mean total, low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol concentrations were higher than those of the control subjects, whereas very low density lipoprotein (VLDL) cholesterol, total and VLDL triglyceride, and total and LDL apolipoprotein B concentrations were not significantly different. Relative to concentrations at three months total and LDL cholesterol and apolipoprotein B concentrations fell markedly, and a slight fall occurred in HDL cholesterol following infarction. VLDL cholesterol and total and VLDL triglyceride were decreased only on day one. Albumin and transferrin concentrations were higher and alpha 1-acid glycoprotein was lower at three months than in the control subjects; alpha 2-macroglobulin, caeruloplasmin, haptoglobin and immunoglobulin IgM were not significantly different. Following infarction albumin and transferrin fell, alpha 2-macroglobulin did not change, and alpha 1-acid glycoprotein, caeruloplasmin, haptoglobin and IgM rose. The changes in both lipids and protein are probably part of the general metabolic response to trauma.", "contents": "Response of plasma lipoproteins and acute phase proteins to myocardial infarction. Plasma concentrations of lipoprotein-lipids, apolipoprotein B (apoB) and of seven other proteins have been estimated serially in 27 patients up to three months following myocardial infarction. Results were compared with those from age- and sex-matched control subjects. At three months the mean total, low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol concentrations were higher than those of the control subjects, whereas very low density lipoprotein (VLDL) cholesterol, total and VLDL triglyceride, and total and LDL apolipoprotein B concentrations were not significantly different. Relative to concentrations at three months total and LDL cholesterol and apolipoprotein B concentrations fell markedly, and a slight fall occurred in HDL cholesterol following infarction. VLDL cholesterol and total and VLDL triglyceride were decreased only on day one. Albumin and transferrin concentrations were higher and alpha 1-acid glycoprotein was lower at three months than in the control subjects; alpha 2-macroglobulin, caeruloplasmin, haptoglobin and immunoglobulin IgM were not significantly different. Following infarction albumin and transferrin fell, alpha 2-macroglobulin did not change, and alpha 1-acid glycoprotein, caeruloplasmin, haptoglobin and IgM rose. The changes in both lipids and protein are probably part of the general metabolic response to trauma."}
{"id": "PMID:227638", "title": "Increased 99mTc-pyrophosphate uptake with radiation pneumonitis.", "content": "A case of radiation pneumonitis confirmed by tissue biopsy is presented with demonstration of increased uptake of 99mTc-pyrophosphate.", "contents": "Increased 99mTc-pyrophosphate uptake with radiation pneumonitis. A case of radiation pneumonitis confirmed by tissue biopsy is presented with demonstration of increased uptake of 99mTc-pyrophosphate."}
{"id": "PMID:227635", "title": "The early clinical presentation of synovial sarcoma.", "content": "While synovial sarcoma most commonly presents as a painless mass, occasionally the cancer emerges in a misleading manner resulting in an unfavorable delay or error in diagnosis. A review of the litrature reveals 4 such occult patterns: pretumor phase characterized only by pain or tenderness; the acute inflammatory lesion presenting as a \"hot\" arthritis or bursitis; the chronic contracture; the post traumatic tumor. These conditions, especially when otherwise unaccounted for, are indications for biopsy. Four avoidable pitfalls in biopsy management also emerged from the review.", "contents": "The early clinical presentation of synovial sarcoma. While synovial sarcoma most commonly presents as a painless mass, occasionally the cancer emerges in a misleading manner resulting in an unfavorable delay or error in diagnosis. A review of the litrature reveals 4 such occult patterns: pretumor phase characterized only by pain or tenderness; the acute inflammatory lesion presenting as a \"hot\" arthritis or bursitis; the chronic contracture; the post traumatic tumor. These conditions, especially when otherwise unaccounted for, are indications for biopsy. Four avoidable pitfalls in biopsy management also emerged from the review."}
{"id": "PMID:227639", "title": "Acyclovir kinetics after intravenous infusion.", "content": "The disposition and safety of the antiviral drug acyclovir were studied in 14 subjects with advanced malignancies. Acyclovir was administered by a 1-hr intravenous infusion at doses of 0.5, 1.0, 2.5, and 5.0 mg/kg. At the end of infusion, mean peak plasma levels (+/- SEM), determined by radioimmunoassay, were 6.4 +/- 0.7, 12.1 +/- 2.3, 14.9 +/- 2.7, and 33.7 +/- 7.1 microM. The plasma concentration-time profiles could be described by a biexponential equation. The half-life of acyclovir in the slow disposition phase ranged from 2.2 to 5 hr and the drug was detected in the plasma for at least 18 hr after infusion. The total body clearance ranged from 117 to 396 ml/min/1.73 m2. A proportionality between area under the curve and dose suggests that acyclovir exhibits dose-independent kinetics in the dose range studied. There was wide variation in cumulative urinary excretion of unchanged drug, ranging from 30 to 69% of the dose. From renal clearances of acyclovir, which were higher than creatinine clearances, it appears that both glomerular filtration and tubular secretion contribute to its renal excretion. Analysis of the urine by reverse-phase high-performance liquid chromatography revealed the presence of the metabolite 9-carboxymethoxymethylguanine. There was no indication of toxicity either clinically or from laboratory findings in any of the study subjects. This study demonstrates that in addition to selectivity and low toxicity, the kinetic profile and metabolic disposition of acyclovir make it an attractive candidate for therapy in a variety of herpes infections.", "contents": "Acyclovir kinetics after intravenous infusion. The disposition and safety of the antiviral drug acyclovir were studied in 14 subjects with advanced malignancies. Acyclovir was administered by a 1-hr intravenous infusion at doses of 0.5, 1.0, 2.5, and 5.0 mg/kg. At the end of infusion, mean peak plasma levels (+/- SEM), determined by radioimmunoassay, were 6.4 +/- 0.7, 12.1 +/- 2.3, 14.9 +/- 2.7, and 33.7 +/- 7.1 microM. The plasma concentration-time profiles could be described by a biexponential equation. The half-life of acyclovir in the slow disposition phase ranged from 2.2 to 5 hr and the drug was detected in the plasma for at least 18 hr after infusion. The total body clearance ranged from 117 to 396 ml/min/1.73 m2. A proportionality between area under the curve and dose suggests that acyclovir exhibits dose-independent kinetics in the dose range studied. There was wide variation in cumulative urinary excretion of unchanged drug, ranging from 30 to 69% of the dose. From renal clearances of acyclovir, which were higher than creatinine clearances, it appears that both glomerular filtration and tubular secretion contribute to its renal excretion. Analysis of the urine by reverse-phase high-performance liquid chromatography revealed the presence of the metabolite 9-carboxymethoxymethylguanine. There was no indication of toxicity either clinically or from laboratory findings in any of the study subjects. This study demonstrates that in addition to selectivity and low toxicity, the kinetic profile and metabolic disposition of acyclovir make it an attractive candidate for therapy in a variety of herpes infections."}
{"id": "PMID:227644", "title": "The physical and genetic organization of a viral genome.", "content": "Mutants of SV40 with deletions of a few to several thousand base pairs have been constructed in vitro and cloned in cultured monkey cells. The location and size of these deletions has been determined by restriction endonuclease mapping and electron microscopic and enzymatic analysis of DNA heteroduplex molecules. Analysis of the phenotype of these deletion mutants permits us to specify the locations of the known SV40 genes, in particular, the novel organization of SV40s two early genes that are required for oncogenesis.", "contents": "The physical and genetic organization of a viral genome. Mutants of SV40 with deletions of a few to several thousand base pairs have been constructed in vitro and cloned in cultured monkey cells. The location and size of these deletions has been determined by restriction endonuclease mapping and electron microscopic and enzymatic analysis of DNA heteroduplex molecules. Analysis of the phenotype of these deletion mutants permits us to specify the locations of the known SV40 genes, in particular, the novel organization of SV40s two early genes that are required for oncogenesis."}
{"id": "PMID:227646", "title": "Acute respiratory failure following severe arsenic poisoning.", "content": "A 47-year-old man had an episode of severe respiratory failure after acute intoxication with arsenic. Features of the initial clinical presentation included nausea, vomiting, and diarrhea, acute psychosis, diffuse skin rash, and marked pancytopenia. A peripheral neuropathy then developed which resulted in severe weakness of all muscles of the limbs, the shoulder and pelvis girdles, and the trunk. The neuropathy continued to progress despite treatment with dimercaprol (BAL in oil). Five weeks after the initial exposure, the patient was no longer able to maintain adquate ventilation and required mechanical ventilatory support. Improvement in the patient's neuromuscular status permitted successful weaning from the ventilator after one month of mechanical ventilation. Long-term follow-up revealed no further respiratory difficulty and slow improvement in the strength of the peripheral muscles.", "contents": "Acute respiratory failure following severe arsenic poisoning. A 47-year-old man had an episode of severe respiratory failure after acute intoxication with arsenic. Features of the initial clinical presentation included nausea, vomiting, and diarrhea, acute psychosis, diffuse skin rash, and marked pancytopenia. A peripheral neuropathy then developed which resulted in severe weakness of all muscles of the limbs, the shoulder and pelvis girdles, and the trunk. The neuropathy continued to progress despite treatment with dimercaprol (BAL in oil). Five weeks after the initial exposure, the patient was no longer able to maintain adquate ventilation and required mechanical ventilatory support. Improvement in the patient's neuromuscular status permitted successful weaning from the ventilator after one month of mechanical ventilation. Long-term follow-up revealed no further respiratory difficulty and slow improvement in the strength of the peripheral muscles."}
{"id": "PMID:227649", "title": "Enzyme replacement and other biochemical approaches to the therapy of adenosine deaminase deficiency.", "content": "Addition of adenosine deaminase (ADA) restored in vitro responses of lymphocytes from a patient with ADA deficiency and severe combined immunodeficiency (SCID). Enzyme replacement therapy, using red blood cells as a source of encapsulated human ADA, restored both T and B cell function in this patient. Ten other ADA--SCID patients have been treated with this form of enzyme replacement and five have responded to therapy. Lymphocytes from ADA--SCID patients treated with enzyme replacement become immunocompetent but remain enzyme deficient. Studies of these cells provide evidence supporting both cyclic AMP- and dATP-mediated immunosuppressive mechanisms in ADA--SCID. These observations suggest that inhibition of cyclic AMP synthesis and/or deoxycytidine (and possibly thymidine) supplementation may be useful new biochemical approaches to the therapy of ADA--SCID.", "contents": "Enzyme replacement and other biochemical approaches to the therapy of adenosine deaminase deficiency. Addition of adenosine deaminase (ADA) restored in vitro responses of lymphocytes from a patient with ADA deficiency and severe combined immunodeficiency (SCID). Enzyme replacement therapy, using red blood cells as a source of encapsulated human ADA, restored both T and B cell function in this patient. Ten other ADA--SCID patients have been treated with this form of enzyme replacement and five have responded to therapy. Lymphocytes from ADA--SCID patients treated with enzyme replacement become immunocompetent but remain enzyme deficient. Studies of these cells provide evidence supporting both cyclic AMP- and dATP-mediated immunosuppressive mechanisms in ADA--SCID. These observations suggest that inhibition of cyclic AMP synthesis and/or deoxycytidine (and possibly thymidine) supplementation may be useful new biochemical approaches to the therapy of ADA--SCID."}
{"id": "PMID:227652", "title": "[Importance of follow-up investigation in colonic carcinoma (author's transl)].", "content": "Extensive follow-up investigations were done in 1978 in 135 patients, most of whom had been operated for colo-rectal carcinoma of all stages in 1977. In 71% of the cases no or no sufficient postoperative control had been performed in the patients' own area. At the follow-up investigations 11 recurrences in the anastomosis, 10 of which were operable, 20 distant metastases, 1 simultaneous second carcinoma, 15 adenomas, partially with numerous atypical cells, 1 polyposis coli and 23 nonspecific granulomas of the anastomosis were detected. The Haemoccult test was positive in 3 of the 11 anastomotic recurrences. Only in cases of distant metastases were values of carcinoembryonic antigen clearly increased (greater than 5 ng/ml). These findings underline the necessity of intensifying the regular follow-up investigation in colo-rectal carcinoma.", "contents": "[Importance of follow-up investigation in colonic carcinoma (author's transl)]. Extensive follow-up investigations were done in 1978 in 135 patients, most of whom had been operated for colo-rectal carcinoma of all stages in 1977. In 71% of the cases no or no sufficient postoperative control had been performed in the patients' own area. At the follow-up investigations 11 recurrences in the anastomosis, 10 of which were operable, 20 distant metastases, 1 simultaneous second carcinoma, 15 adenomas, partially with numerous atypical cells, 1 polyposis coli and 23 nonspecific granulomas of the anastomosis were detected. The Haemoccult test was positive in 3 of the 11 anastomotic recurrences. Only in cases of distant metastases were values of carcinoembryonic antigen clearly increased (greater than 5 ng/ml). These findings underline the necessity of intensifying the regular follow-up investigation in colo-rectal carcinoma."}
{"id": "PMID:227659", "title": "Radioiodinated nondegradable gonadotropin-releasing hormone analogs: new probes for the investigation of pituitary gonadotropin-releasing hormone receptors.", "content": "Studies of pituitary plasma membrane gonadotropin-releasing hormone (GnRH) receptors using [125I]-iodo-GnRH suffer major disadvantages. Only a small (less than 25%) proportion of specific tracer binding is to high affinity sites, with more than 70% bound to low affinity sites (Ka = 1 x 10(6) M-1). [125I]Iodo-GnRH is also inactivated during incubation with pituitary plasma membrane preparations. Two superactive analongs of GnRH, substituted in positions 6 and 10, were used as the labeled ligand to overcome these problems. Both analogs bound to the same high affinity sites as GnRH on bovine pituitary plasma membranes, though the affinity of the analogs was higher than that of the natural decapeptide (Ka = 2.0 x 10(9), 6.0 x 10(9), and 3.0 x 10(8) M-1 for [D-Ser(TBu)6]des-Gly10-GnRH ethylamide, [D-Ala6]des-Gly10-GnRH ethylamide, and GnRH, respectively. The labeled analogs bound to a single class of high affinity sites with less than 15% of the specific binding being to low affinity sites (Ka approximately equal to 1 x 10(6) M-1). The labeled analogs were not inactivated during incubation with the pituitary membrane preparations. Using the analogs as tracer, a single class of high affinity sites (K1 = 4.0 x 10(9) M-1) was also demonstrated on crude 10,800 x g rat pituitary membrane preparations. Use of these analogs as both the labeled and unlabeled ligand offers substantial advantages over GnRH for investigation of GnRH receptors, allowing accurate determination of changes in their numbers and affinities under various physiological conditions.", "contents": "Radioiodinated nondegradable gonadotropin-releasing hormone analogs: new probes for the investigation of pituitary gonadotropin-releasing hormone receptors. Studies of pituitary plasma membrane gonadotropin-releasing hormone (GnRH) receptors using [125I]-iodo-GnRH suffer major disadvantages. Only a small (less than 25%) proportion of specific tracer binding is to high affinity sites, with more than 70% bound to low affinity sites (Ka = 1 x 10(6) M-1). [125I]Iodo-GnRH is also inactivated during incubation with pituitary plasma membrane preparations. Two superactive analongs of GnRH, substituted in positions 6 and 10, were used as the labeled ligand to overcome these problems. Both analogs bound to the same high affinity sites as GnRH on bovine pituitary plasma membranes, though the affinity of the analogs was higher than that of the natural decapeptide (Ka = 2.0 x 10(9), 6.0 x 10(9), and 3.0 x 10(8) M-1 for [D-Ser(TBu)6]des-Gly10-GnRH ethylamide, [D-Ala6]des-Gly10-GnRH ethylamide, and GnRH, respectively. The labeled analogs bound to a single class of high affinity sites with less than 15% of the specific binding being to low affinity sites (Ka approximately equal to 1 x 10(6) M-1). The labeled analogs were not inactivated during incubation with the pituitary membrane preparations. Using the analogs as tracer, a single class of high affinity sites (K1 = 4.0 x 10(9) M-1) was also demonstrated on crude 10,800 x g rat pituitary membrane preparations. Use of these analogs as both the labeled and unlabeled ligand offers substantial advantages over GnRH for investigation of GnRH receptors, allowing accurate determination of changes in their numbers and affinities under various physiological conditions."}
{"id": "PMID:227662", "title": "Effect of tetradecapeptide renin substrate on blood pressure, plasma renin activity, and vasopressin and adrenocorticotropin concentrations.", "content": "The effects of third ventricular injection of tetradecapeptide renin substrate (TDP) and natural renin substrate prepared from dog cerebrospinal fluid were compared in anesthetized dogs. Central injection of 350 pmol TDP caused a long lasting increase in arterial blood pressure, a reduction in PRA, and increases in plasma levels of vasopressin, and ACTH. In marked contrast, central administration of equimolar doses of natural renin substrate had no effect on these variables. Intracranial administration of the converting enzyme inhibitor SQ 20881 prevented the effects of central injection of TDP. Thus, TDP exerts its effects via conversion to angiotensin II and does not necessitate the postulation of the action of an enzyme with renin-like activity in the brain.", "contents": "Effect of tetradecapeptide renin substrate on blood pressure, plasma renin activity, and vasopressin and adrenocorticotropin concentrations. The effects of third ventricular injection of tetradecapeptide renin substrate (TDP) and natural renin substrate prepared from dog cerebrospinal fluid were compared in anesthetized dogs. Central injection of 350 pmol TDP caused a long lasting increase in arterial blood pressure, a reduction in PRA, and increases in plasma levels of vasopressin, and ACTH. In marked contrast, central administration of equimolar doses of natural renin substrate had no effect on these variables. Intracranial administration of the converting enzyme inhibitor SQ 20881 prevented the effects of central injection of TDP. Thus, TDP exerts its effects via conversion to angiotensin II and does not necessitate the postulation of the action of an enzyme with renin-like activity in the brain."}
{"id": "PMID:227663", "title": "Follicle-stimulating hormone-induced, adenosine 3',5'-monophosphate-mediated movement of immature rat sertoli cells in primary culture.", "content": "Sertoli cells dissociated from 10-day-old rat testes form colonies in primary culture in response to FSH. FSH and dibutyryl cAMP stimulated the attachment of Sertoli cells to an equal extent; however, FSH-treated cultures contained a small number of large colonies while dibutyryl cAMP-treated cultures contained a large number of small colonies. This relationship was not altered by the addition of a number of other peptide or steroid hormones. Extracellular cAMP levels and colony density were negatively correlated. Colony size at 24 h of culture was diminished in FSH-treated cultures by the addition of a cAMP antibody at 6 or 12 h of incubation. The addition of cAMP at 24 h to FSH-treated cultures caused a dose-dependent stimulation of colony size but not colony density at 48 h of culture. A point source of cAMP (4 x 10(-3) M in agar) inhibited migration of cells toward the agar spot. An agar spot on the dish substratum containing Sepharose-bound FSH exhibited a halo of cells next to the spot, with a zone lacking cells distal to it. Radioautographs of [125I]iodo-FSH-treated cultures exhibited a nonhomogeneous distribution of silver grains; colony size increased faster than the number of labeled cells. Taken together, the results suggest that 1) FSH is stimulating the attachment of Sertoli cells through an increase in intracellular cAMP, 2) FSH is promoting active aggregation of Sertoli cells in culture through a modulation of extracellular cAMP, and 3) cells with a large amount of bound FSH are acting as centers for aggregation.", "contents": "Follicle-stimulating hormone-induced, adenosine 3',5'-monophosphate-mediated movement of immature rat sertoli cells in primary culture. Sertoli cells dissociated from 10-day-old rat testes form colonies in primary culture in response to FSH. FSH and dibutyryl cAMP stimulated the attachment of Sertoli cells to an equal extent; however, FSH-treated cultures contained a small number of large colonies while dibutyryl cAMP-treated cultures contained a large number of small colonies. This relationship was not altered by the addition of a number of other peptide or steroid hormones. Extracellular cAMP levels and colony density were negatively correlated. Colony size at 24 h of culture was diminished in FSH-treated cultures by the addition of a cAMP antibody at 6 or 12 h of incubation. The addition of cAMP at 24 h to FSH-treated cultures caused a dose-dependent stimulation of colony size but not colony density at 48 h of culture. A point source of cAMP (4 x 10(-3) M in agar) inhibited migration of cells toward the agar spot. An agar spot on the dish substratum containing Sepharose-bound FSH exhibited a halo of cells next to the spot, with a zone lacking cells distal to it. Radioautographs of [125I]iodo-FSH-treated cultures exhibited a nonhomogeneous distribution of silver grains; colony size increased faster than the number of labeled cells. Taken together, the results suggest that 1) FSH is stimulating the attachment of Sertoli cells through an increase in intracellular cAMP, 2) FSH is promoting active aggregation of Sertoli cells in culture through a modulation of extracellular cAMP, and 3) cells with a large amount of bound FSH are acting as centers for aggregation."}
{"id": "PMID:227664", "title": "Study of oxytocin receptor in human myometrium using highly specific 3H-labeled oxytocin.", "content": "A highly specific tritium labeled oxytocin (3H-OT) was synthesized utilizing the method of catalytic substitution of halogen for hydrogen. The specific activity of 3H-OT was 19 Ci/mM and the biologic activity was 350 U/mg, which was sufficient for the OT radioreceptor assay. The maximum % uptake of 3H-OT in the human myometrium was observed in 20,000 X g pellets under the optimal conditions of pH 7.4, at 20 degrees C and the incubation time of 90 min and it was augmented in the presence of Mn++. It was observed from the Scatchard plot, that the binding site of OT in the human myometrial specimens was a single type within the range of OT concentration of 0.4 nM to 1.6 nM. The dissociation constants (Kd) and the number of binding sites (NBS) showed a relative increase as gestation advance. The apparent Kd of term pregnancies was 1.25 X 10(-9) M regardless of the presence or absence of labor pains, while the NBS of term pregnancies with and without labor pain was 1.2 X 10(-12) and 4.7 X 10(-12) moles/mg, protein, respectively.", "contents": "Study of oxytocin receptor in human myometrium using highly specific 3H-labeled oxytocin. A highly specific tritium labeled oxytocin (3H-OT) was synthesized utilizing the method of catalytic substitution of halogen for hydrogen. The specific activity of 3H-OT was 19 Ci/mM and the biologic activity was 350 U/mg, which was sufficient for the OT radioreceptor assay. The maximum % uptake of 3H-OT in the human myometrium was observed in 20,000 X g pellets under the optimal conditions of pH 7.4, at 20 degrees C and the incubation time of 90 min and it was augmented in the presence of Mn++. It was observed from the Scatchard plot, that the binding site of OT in the human myometrial specimens was a single type within the range of OT concentration of 0.4 nM to 1.6 nM. The dissociation constants (Kd) and the number of binding sites (NBS) showed a relative increase as gestation advance. The apparent Kd of term pregnancies was 1.25 X 10(-9) M regardless of the presence or absence of labor pains, while the NBS of term pregnancies with and without labor pain was 1.2 X 10(-12) and 4.7 X 10(-12) moles/mg, protein, respectively."}
{"id": "PMID:227665", "title": "Induction of specific human growth hormone binding sites in rat liver by human growth hormone.", "content": "125I-Labeled hGH was bound to liver plasma membranes which were obtained from female rats. The binding was displaced by hGH, hPRL, bPRL, rPRL and bGH but not by rGH. This result indicated that hGH was bound to lactogenic binding sites in rat livers. After hypophysectomy, the binding was markedly decreased. Treatment of hypophysectomized rats with hGH (80 micrograms/day) for 10 days increased the binding sites for hGH. These binding sites were different from those found in normal female rat livers because of their high affinity and specificity for hGH. These results indicate that hGH induces specific binding sites for hGH in rat livers.", "contents": "Induction of specific human growth hormone binding sites in rat liver by human growth hormone. 125I-Labeled hGH was bound to liver plasma membranes which were obtained from female rats. The binding was displaced by hGH, hPRL, bPRL, rPRL and bGH but not by rGH. This result indicated that hGH was bound to lactogenic binding sites in rat livers. After hypophysectomy, the binding was markedly decreased. Treatment of hypophysectomized rats with hGH (80 micrograms/day) for 10 days increased the binding sites for hGH. These binding sites were different from those found in normal female rat livers because of their high affinity and specificity for hGH. These results indicate that hGH induces specific binding sites for hGH in rat livers."}
{"id": "PMID:227667", "title": "Effects of ischemia on the removal of extracellular potassium in cat cortex during pentylenetetrazol seizures.", "content": "Changes in cortical extracellular potassium activity ([K+]0), NADH fluorescence, and oxygen consumption were studied in anesthetized cats during pentylenetetrazol seizures. The effects of partial ischemia induced by either hypotension or intermittent carotid artery occlusion on these parameters were investigated. Nonischemic seizures were characterized by gradual generalized decreases in cortical NADH fluorescence and increases in O2 consumption, along with rapid increases in [K+]0, which then usually fell slightly as the ictal discharge continued. Ischemic seizures, on the other hand, were accompanied by complex changes in NADH fluorescence, by smaller delayed maximal increases in O2 consumption that lasted beyond the end of ictal activity, and by more sustained increases in [K+]0. The decay of [K+]0 after the termination of seizures in both nonischemic and moderately ischemic animals was not a monoexponential function: plots of ln delta [K+]0 versus time showed an initial linear decline (of slope M1) that rather abruptly slowed (to slope M2) after 2 to 5 sec and then often increased to the original rate. Both M1 and M2 were proportionately decreased by ischemia. In addition, the rate of [K+]0 removal could be slowed by acute ischemia induced either during or after the end of ictal activity. The initial rate of postictal [K+]0 removal (M1) was found to be linearly and inversely related to the level of cortical NADH fluorescence at the time of seizure termination. The results of this study suggest that an O2-dependent transport mechanism plays a major role in the removal of [K+]0 during and following the termination of generalized pentylenetetrazol seizures in the cat.", "contents": "Effects of ischemia on the removal of extracellular potassium in cat cortex during pentylenetetrazol seizures. Changes in cortical extracellular potassium activity ([K+]0), NADH fluorescence, and oxygen consumption were studied in anesthetized cats during pentylenetetrazol seizures. The effects of partial ischemia induced by either hypotension or intermittent carotid artery occlusion on these parameters were investigated. Nonischemic seizures were characterized by gradual generalized decreases in cortical NADH fluorescence and increases in O2 consumption, along with rapid increases in [K+]0, which then usually fell slightly as the ictal discharge continued. Ischemic seizures, on the other hand, were accompanied by complex changes in NADH fluorescence, by smaller delayed maximal increases in O2 consumption that lasted beyond the end of ictal activity, and by more sustained increases in [K+]0. The decay of [K+]0 after the termination of seizures in both nonischemic and moderately ischemic animals was not a monoexponential function: plots of ln delta [K+]0 versus time showed an initial linear decline (of slope M1) that rather abruptly slowed (to slope M2) after 2 to 5 sec and then often increased to the original rate. Both M1 and M2 were proportionately decreased by ischemia. In addition, the rate of [K+]0 removal could be slowed by acute ischemia induced either during or after the end of ictal activity. The initial rate of postictal [K+]0 removal (M1) was found to be linearly and inversely related to the level of cortical NADH fluorescence at the time of seizure termination. The results of this study suggest that an O2-dependent transport mechanism plays a major role in the removal of [K+]0 during and following the termination of generalized pentylenetetrazol seizures in the cat."}
{"id": "PMID:227668", "title": "Carcinogenicity of chloroform.", "content": "Chloroform is carcinogenic in rats, mice, and probably in dogs. Chloroform induced carcinomas of the liver and kidney and malignant tumors in other organs in rats and mice. Liver neoplasms have been described in three strains of mice. Carcinomas of the kidney were found in a first study in mice and in the repeat of that study. Dogs given chloroform developed neoplasms of the liver as well as in other organs. Rats given chloroform also developed toxic changes, particularly male rats, as a result of treatment. These lesions included interstitial fibrosis of the kidney; polyarteritis of the mesenteric, pancreatic, and other arterioles and arteries; and atrophy of the testes. These toxic changes may have interfered with the development of neoplasms in male rats.", "contents": "Carcinogenicity of chloroform. Chloroform is carcinogenic in rats, mice, and probably in dogs. Chloroform induced carcinomas of the liver and kidney and malignant tumors in other organs in rats and mice. Liver neoplasms have been described in three strains of mice. Carcinomas of the kidney were found in a first study in mice and in the repeat of that study. Dogs given chloroform developed neoplasms of the liver as well as in other organs. Rats given chloroform also developed toxic changes, particularly male rats, as a result of treatment. These lesions included interstitial fibrosis of the kidney; polyarteritis of the mesenteric, pancreatic, and other arterioles and arteries; and atrophy of the testes. These toxic changes may have interfered with the development of neoplasms in male rats."}
{"id": "PMID:227679", "title": "Effect of sciatic nerve crush on enzyme activities of skeletal muscles of the rat.", "content": "Weight loss and reduction in specific activity of cytochrome oxidase of both red (soleus) and white muscles (gastrocnemius and plantaris) of the rat was greatest 5 days after sciatic nerve crush (p less than 0.001) and then became minimal. In neither was there a significant, concomitant loss of protein. By 19 days, the specific activity of cytochrome oxidase was the same in both muscle types. The specific activity of lactate dehydrogenase was reduced significantly (p less than 0.001) in the white muscles, to a value approaching that of the red soleus by 19 days postoperatively, but remained unaltered in the soleus. Nerve crush is proposed as a model experimental system for studying neural regulation of skeletal muscle metabolism.", "contents": "Effect of sciatic nerve crush on enzyme activities of skeletal muscles of the rat. Weight loss and reduction in specific activity of cytochrome oxidase of both red (soleus) and white muscles (gastrocnemius and plantaris) of the rat was greatest 5 days after sciatic nerve crush (p less than 0.001) and then became minimal. In neither was there a significant, concomitant loss of protein. By 19 days, the specific activity of cytochrome oxidase was the same in both muscle types. The specific activity of lactate dehydrogenase was reduced significantly (p less than 0.001) in the white muscles, to a value approaching that of the red soleus by 19 days postoperatively, but remained unaltered in the soleus. Nerve crush is proposed as a model experimental system for studying neural regulation of skeletal muscle metabolism."}
{"id": "PMID:227680", "title": "Effect of air ionization on heart rate and perceived exertion during a bicycle exercise test. A double-blind cross-over study.", "content": "The influence of ionization of air on heart rate (HR) and ratings of perceived exertion (RPE) during bicycle exercise was studied in nine healthy medical students selected according to a randomized schedule from the class of 90 students. The exercise tests were performed both under negative and positive ionization. The study was made with a double-blind, cross-over design. The body surface exposed to ionic current was made large by reducing the clothing of the subject. A significant overall tendency to lower HR and RPE values under negative ionization was observed (p less than 0.01, sign tests). The RPE values were significantly lower (p less than 0.01, paired t-test and the Wilcoxon test) under negative than under positive ionization at the maximal work load level but not at other relative load levels. However, when separately tested at each relative load level HR values did not differ significantly in negative and positive ionization. The results of this pilot study indicate that ionic composition of the air can modify the RPE and possibly also HR during exercise; negative air ionization seems to be beneficial compared with positive ionization. The mechanisms involved are obscure, but we suggest that negative ionization of air may increase oxidative metabolism through generation of a superoxide radical (O2-) that is reduced to H2O2 by superoxide dismutases.", "contents": "Effect of air ionization on heart rate and perceived exertion during a bicycle exercise test. A double-blind cross-over study. The influence of ionization of air on heart rate (HR) and ratings of perceived exertion (RPE) during bicycle exercise was studied in nine healthy medical students selected according to a randomized schedule from the class of 90 students. The exercise tests were performed both under negative and positive ionization. The study was made with a double-blind, cross-over design. The body surface exposed to ionic current was made large by reducing the clothing of the subject. A significant overall tendency to lower HR and RPE values under negative ionization was observed (p less than 0.01, sign tests). The RPE values were significantly lower (p less than 0.01, paired t-test and the Wilcoxon test) under negative than under positive ionization at the maximal work load level but not at other relative load levels. However, when separately tested at each relative load level HR values did not differ significantly in negative and positive ionization. The results of this pilot study indicate that ionic composition of the air can modify the RPE and possibly also HR during exercise; negative air ionization seems to be beneficial compared with positive ionization. The mechanisms involved are obscure, but we suggest that negative ionization of air may increase oxidative metabolism through generation of a superoxide radical (O2-) that is reduced to H2O2 by superoxide dismutases."}
{"id": "PMID:227681", "title": "The control of phosphoprotein phosphatase by the second-site phosphorylation of a substrate. Studies with H2B histone as model substrate.", "content": "The phosphorylation of Ser-32, in addition to Ser-36 of H2B histone, stimulated the rate of Pi release from Ser-36 by the small form (Mr 31 000) of pig heart phosphoprotein phosphatase both in the absence and presence of 50 mM magnesium acetate. By phosphorylation at Ser-32, the Km value for Ser-36 phosphate in H2B histone was increased from 0.38 microM to 1.16 microM in the absence of magnesium acetate, but not significantly changed (from 37.4 microM to 26.2 microM) in the presence of magnesium acetate. With the large form (Mr 224000) of the phosphoprotein phosphatase, however, the phosphorylation at Ser-32 suppressed the rate of Pi release from Ser-36 both in the absence and presence of magnesium acetate. The Km value of the large form for Ser-36 phosphatase in H2B histone was nevertheless increased by phosphorylation at Ser-32, from 1.2 microM to 5.3 microM in the presence of magnesium acetate, but not changed (from 0.26 microM to 0.23 microM) in the absence of magnesium acetate.", "contents": "The control of phosphoprotein phosphatase by the second-site phosphorylation of a substrate. Studies with H2B histone as model substrate. The phosphorylation of Ser-32, in addition to Ser-36 of H2B histone, stimulated the rate of Pi release from Ser-36 by the small form (Mr 31 000) of pig heart phosphoprotein phosphatase both in the absence and presence of 50 mM magnesium acetate. By phosphorylation at Ser-32, the Km value for Ser-36 phosphate in H2B histone was increased from 0.38 microM to 1.16 microM in the absence of magnesium acetate, but not significantly changed (from 37.4 microM to 26.2 microM) in the presence of magnesium acetate. With the large form (Mr 224000) of the phosphoprotein phosphatase, however, the phosphorylation at Ser-32 suppressed the rate of Pi release from Ser-36 both in the absence and presence of magnesium acetate. The Km value of the large form for Ser-36 phosphatase in H2B histone was nevertheless increased by phosphorylation at Ser-32, from 1.2 microM to 5.3 microM in the presence of magnesium acetate, but not changed (from 0.26 microM to 0.23 microM) in the absence of magnesium acetate."}
{"id": "PMID:227682", "title": "Evidence for a second desensitized state of beta-adrenergic receptor with low affinity for beta-antagonists and normal reactivity towards beta-agonists in adipocyte membranes previously exposed to beta-antagonists.", "content": "When adipocyte membranes are successively exposed to (-)-propranolol or (+/- alprenolol at 25 or 4 degrees C, repeatedly washed and then assayed for (-)-[3H]dihydroalprenolol binding, the apparent number of beta-adrenergic binding sites is markedly decreased. Induction of this peculiar type of receptor desensitization does not require prolonged exposure of the membranes to the beta-adrenergic antagonists (half-time: 1 min), is stereospecific, concentration-dependent and almost complete with high concentrations of antagonists. p[NH]ppG, which reduces the affinity of fat cell beta-adrenergic receptors for agonists, does not prevent the antagonist-induced decrease in the receptor number. The magnitude of the desensitizating effect induced separately by (-)-isoproterenol and (-)-propranolol is not additive in membranes exposed to both drugs, suggesting that the receptors lost after exposure to agonists are the same sites as part of those lost after exposure to antagonists. However, contrary to the results found in membranes desensitized by agonists, adenylate cyclase activity remained fully responsive to catecholamines in membranes exposed to beta-antagonists. As shown by kinetic studies on (-)-[3H]dihydroalprenolol binding, this beta-antagonist-induced receptor desensitization is reversible after prolonged incubation. These data which have never yet been described in the other reported desensitizable beta-adrenergic systems, suggest that, when exposed to beta-antagonists, the fat cell beta-adrenergic receptors undergo a conformational change leading to a peculiar state which has low affinity for antagonists but behaves towards agonists as does the receptor in its resting state.", "contents": "Evidence for a second desensitized state of beta-adrenergic receptor with low affinity for beta-antagonists and normal reactivity towards beta-agonists in adipocyte membranes previously exposed to beta-antagonists. When adipocyte membranes are successively exposed to (-)-propranolol or (+/- alprenolol at 25 or 4 degrees C, repeatedly washed and then assayed for (-)-[3H]dihydroalprenolol binding, the apparent number of beta-adrenergic binding sites is markedly decreased. Induction of this peculiar type of receptor desensitization does not require prolonged exposure of the membranes to the beta-adrenergic antagonists (half-time: 1 min), is stereospecific, concentration-dependent and almost complete with high concentrations of antagonists. p[NH]ppG, which reduces the affinity of fat cell beta-adrenergic receptors for agonists, does not prevent the antagonist-induced decrease in the receptor number. The magnitude of the desensitizating effect induced separately by (-)-isoproterenol and (-)-propranolol is not additive in membranes exposed to both drugs, suggesting that the receptors lost after exposure to agonists are the same sites as part of those lost after exposure to antagonists. However, contrary to the results found in membranes desensitized by agonists, adenylate cyclase activity remained fully responsive to catecholamines in membranes exposed to beta-antagonists. As shown by kinetic studies on (-)-[3H]dihydroalprenolol binding, this beta-antagonist-induced receptor desensitization is reversible after prolonged incubation. These data which have never yet been described in the other reported desensitizable beta-adrenergic systems, suggest that, when exposed to beta-antagonists, the fat cell beta-adrenergic receptors undergo a conformational change leading to a peculiar state which has low affinity for antagonists but behaves towards agonists as does the receptor in its resting state."}
{"id": "PMID:227683", "title": "Conversion of a mitochondrial precursor polypeptide into subunit 1 of cytochrome oxidase in the mi-3 mutant of Neurospora crassa.", "content": "1. The cytochrome-alpha alpha 3-deficient mi-3 cytoplasmic mutant of Neurospora crassa synthesizes a mitochondrial translation product which crossreacts with antibodies specific to subunit 1 of cytochrome oxidase. The immunoprecipitated polypeptide migrates more slowly during gel electrophoresis than the authentic 41 000-Mr subunit 1 of the wild-type enzyme. An apparent molecular weight of about 45 000 was estimated for the mutant product. 2. Radioactive labelling experiments in vivo show that the crossreacting material found in the mutant is relatively stable and does not form complexes with other subunits of the oxidase. 3. After induction of a functional cytochrome oxidase in the mutant cells with antimycin A, the 45 000-Mr polypeptide is converted to a 41 000-Mr component, which exhibits the same electrophoretic mobility as subunit 1 of the oxidase. Pulse-chase labelling kinetics reveal a typical precursor product relationship. 4. The converted polypeptide becomes assembled with other enzyme subunits to form a protein complex which has the immunological characteristics of cytochrome oxidase. A possible physiological role of the post-translational processing of the mitochondrially synthesized component is discussed.", "contents": "Conversion of a mitochondrial precursor polypeptide into subunit 1 of cytochrome oxidase in the mi-3 mutant of Neurospora crassa. 1. The cytochrome-alpha alpha 3-deficient mi-3 cytoplasmic mutant of Neurospora crassa synthesizes a mitochondrial translation product which crossreacts with antibodies specific to subunit 1 of cytochrome oxidase. The immunoprecipitated polypeptide migrates more slowly during gel electrophoresis than the authentic 41 000-Mr subunit 1 of the wild-type enzyme. An apparent molecular weight of about 45 000 was estimated for the mutant product. 2. Radioactive labelling experiments in vivo show that the crossreacting material found in the mutant is relatively stable and does not form complexes with other subunits of the oxidase. 3. After induction of a functional cytochrome oxidase in the mutant cells with antimycin A, the 45 000-Mr polypeptide is converted to a 41 000-Mr component, which exhibits the same electrophoretic mobility as subunit 1 of the oxidase. Pulse-chase labelling kinetics reveal a typical precursor product relationship. 4. The converted polypeptide becomes assembled with other enzyme subunits to form a protein complex which has the immunological characteristics of cytochrome oxidase. A possible physiological role of the post-translational processing of the mitochondrially synthesized component is discussed."}
{"id": "PMID:227684", "title": "Regulation of transcription by DNA-bound non-histone nuclear proteins.", "content": "Purified non-histone proteins from mouse mammary cells bind specifically to homologous DNA or chromatin. Complexes of non-histone protein with DNA or chromatin, isolated on agarose columns, were transcribed with both Escherichia coli RNA polymerase and RNA polymerase B from calf thymus. The fact that complexing of DNA with non-histone proteins increases transcription by E. coli RNA polymerase but not by RNA polymerase B suggests different mechanisms of transcription by these two enzymes. Similar experiments with mouse and Drosophila chromatin indicate that non-histone proteins specifically stimulate the transcription of mouse chromatin by RNA polymerase B. Non-histone proteins stimulate the transcription of mouse mammary tumor virus sequences in chromatin by RNA polymerase B but not by E. coli RNA polymerase. We conclude that those non-histone proteins bound specifically to chromatin are able to activate the transcription of specific genes by eukaryotic RNA polymerase.", "contents": "Regulation of transcription by DNA-bound non-histone nuclear proteins. Purified non-histone proteins from mouse mammary cells bind specifically to homologous DNA or chromatin. Complexes of non-histone protein with DNA or chromatin, isolated on agarose columns, were transcribed with both Escherichia coli RNA polymerase and RNA polymerase B from calf thymus. The fact that complexing of DNA with non-histone proteins increases transcription by E. coli RNA polymerase but not by RNA polymerase B suggests different mechanisms of transcription by these two enzymes. Similar experiments with mouse and Drosophila chromatin indicate that non-histone proteins specifically stimulate the transcription of mouse chromatin by RNA polymerase B. Non-histone proteins stimulate the transcription of mouse mammary tumor virus sequences in chromatin by RNA polymerase B but not by E. coli RNA polymerase. We conclude that those non-histone proteins bound specifically to chromatin are able to activate the transcription of specific genes by eukaryotic RNA polymerase."}
{"id": "PMID:227685", "title": "The calcium-dependent phosphatidylinositol-phosphodiesterase of rat brain. Mechanisms of suppression and stimulation.", "content": "1. The activity of the soluble, calcium-dependent phosphatidylinositol-specific phosphodiesterase (EC 3.1.4.10) against [32P]phosphatidylinositol has been investigated. 2. KC1 (only at neutral pH), Mg2+, positively-charged proteins such as histone, and phospholipids containing a choline headgroup are all inhibitory to the enzyme. Choline-phospholipids cause a 90% inhibition at an equimolar ratio to phosphatidylinositol. 3. Other phospholipids (phosphatidylglycerol, phosphatidylserine, phosphatidylethanolamine and phosphatidic acid) are all potent stimulators of the enzyme: maximum stimulation being observed at a ratio of 1 mol activator/5--10 mol phosphatidylinositol. 4. Unsaturated amphiphiles such as oleic and oleoyl alcohol also stimulate the activity, maximum stimulation being observed at about an equimolar ratio to phosphatidylinositol. Saturated amphiphiles (such as stearic acid and stearoyl alcohol) are less effective. 5. The activation by acidic phospholipids and unsaturated amphiphiles appear to be independent as they are additive and, under certain conditions, synergistic. 6. Both types of stimulator (independently or together) can reverse the inhibition caused by histone or phosphatidylcholine. 7. Possible mechanisms of the suppression of the phosphatidylinositol phosphodiesterase in vivo, of its activation, and of the amplification of phosphatidylinositol breakdown are discussed.", "contents": "The calcium-dependent phosphatidylinositol-phosphodiesterase of rat brain. Mechanisms of suppression and stimulation. 1. The activity of the soluble, calcium-dependent phosphatidylinositol-specific phosphodiesterase (EC 3.1.4.10) against [32P]phosphatidylinositol has been investigated. 2. KC1 (only at neutral pH), Mg2+, positively-charged proteins such as histone, and phospholipids containing a choline headgroup are all inhibitory to the enzyme. Choline-phospholipids cause a 90% inhibition at an equimolar ratio to phosphatidylinositol. 3. Other phospholipids (phosphatidylglycerol, phosphatidylserine, phosphatidylethanolamine and phosphatidic acid) are all potent stimulators of the enzyme: maximum stimulation being observed at a ratio of 1 mol activator/5--10 mol phosphatidylinositol. 4. Unsaturated amphiphiles such as oleic and oleoyl alcohol also stimulate the activity, maximum stimulation being observed at about an equimolar ratio to phosphatidylinositol. Saturated amphiphiles (such as stearic acid and stearoyl alcohol) are less effective. 5. The activation by acidic phospholipids and unsaturated amphiphiles appear to be independent as they are additive and, under certain conditions, synergistic. 6. Both types of stimulator (independently or together) can reverse the inhibition caused by histone or phosphatidylcholine. 7. Possible mechanisms of the suppression of the phosphatidylinositol phosphodiesterase in vivo, of its activation, and of the amplification of phosphatidylinositol breakdown are discussed."}
{"id": "PMID:227686", "title": "Kinetic mechanism of NADH-dependent glutamate synthase from lupin nodules.", "content": "From initial-rate studies, a partially random kinetic mechanism has been deduced for NADH-dependent glutamate synthase from lupin nodules. The mechanism involves compulsory binding of NADH as first substrate, followed by random-order binding of glutamine and 2-oxoglutarate. Patterns of inhibition by glutamate substantiate the mechanism. Dithionite was incapable of acting as an alternative reducing substrate although it is known to reduce the flavine groups of the enzyme. The implications of these results are discussed. Published rate equations for this type of mechanism were found to be unsatisfactory for this enzyme and suitable new equations are produced. These equations should have general application where the obligatory first substrate binds very tightly.", "contents": "Kinetic mechanism of NADH-dependent glutamate synthase from lupin nodules. From initial-rate studies, a partially random kinetic mechanism has been deduced for NADH-dependent glutamate synthase from lupin nodules. The mechanism involves compulsory binding of NADH as first substrate, followed by random-order binding of glutamine and 2-oxoglutarate. Patterns of inhibition by glutamate substantiate the mechanism. Dithionite was incapable of acting as an alternative reducing substrate although it is known to reduce the flavine groups of the enzyme. The implications of these results are discussed. Published rate equations for this type of mechanism were found to be unsatisfactory for this enzyme and suitable new equations are produced. These equations should have general application where the obligatory first substrate binds very tightly."}
{"id": "PMID:227687", "title": "NAD-dependent formate dehydrogenase from methylotrophic bacterium, strain 1. Purification and characterization.", "content": "1. NAD-dependent formate dehydrogenase was isolated from gram-negative methylotrophic bacteria, strain 1, grown on methanol. The purification procedure involved ammonium sulfate fractionation, ion-exchange chromatography and preparative isotachophoresis or gel filtration; it resulted in a yield of 40%. 2. The final enzyme preparations were homogeneous as judged by sedimentation in an ultracentrifuge. Formate dehydrogenase purified in the presence of EDTA reveals two bands on electrophoresis in polyacrylamide gel both after protein and activity staining. Two components are transformed into a single one after prolonged storage in the presence of 2-mercaptoethanol. 3. Formate dehydrogenase is a dimer composed of identical or very similar subunits. The molecular weight of the enzyme is about 80 000. 4. Amino acid composition and some other physico-chemical properties of the enzyme were studied. 5. Formate dehydrogenase is specific for formate and NAD as electron acceptor. The Michaelis constant was 0.11 mM for NAD and 15 mM for formate (pH 7.0, 37 degrees C). 6. Formate dehydrogenase was rapidly inactivated in the absence of -SH compounds. The enzyme retained full activity upon storage at ambient temperature in solution for half a year in the presence of 2-mercaptoethanol or EDTA.", "contents": "NAD-dependent formate dehydrogenase from methylotrophic bacterium, strain 1. Purification and characterization. 1. NAD-dependent formate dehydrogenase was isolated from gram-negative methylotrophic bacteria, strain 1, grown on methanol. The purification procedure involved ammonium sulfate fractionation, ion-exchange chromatography and preparative isotachophoresis or gel filtration; it resulted in a yield of 40%. 2. The final enzyme preparations were homogeneous as judged by sedimentation in an ultracentrifuge. Formate dehydrogenase purified in the presence of EDTA reveals two bands on electrophoresis in polyacrylamide gel both after protein and activity staining. Two components are transformed into a single one after prolonged storage in the presence of 2-mercaptoethanol. 3. Formate dehydrogenase is a dimer composed of identical or very similar subunits. The molecular weight of the enzyme is about 80 000. 4. Amino acid composition and some other physico-chemical properties of the enzyme were studied. 5. Formate dehydrogenase is specific for formate and NAD as electron acceptor. The Michaelis constant was 0.11 mM for NAD and 15 mM for formate (pH 7.0, 37 degrees C). 6. Formate dehydrogenase was rapidly inactivated in the absence of -SH compounds. The enzyme retained full activity upon storage at ambient temperature in solution for half a year in the presence of 2-mercaptoethanol or EDTA."}
{"id": "PMID:227688", "title": "Use of protein-mediated lipid exchange in the study of membrane-bound enzymes. The lipid dependence of glucose-6-phosphatase.", "content": "The ability of liver lipid-exchange proteins to introduce foreign phospholipids into microsomes was used in a study of the lipid dependence of glucose-6-phosphatase. Supplementation of intact rat liver and hepatoma microsomes with exogeneous aminophospholipids prevents the decline of glucose-6-phosphatase activity during incubation, whereas the introduction of exogeneous phosphatidylcholine has no protective effect. On the contrary with deoxycholate-disrupted hepatoma microsomes, introduction of additional phosphatidylcholine causes activation while phosphatidylethanolamine has only little effect. The results are explained by assuming that the transport unit and the catalytic moiety of the glucose-6-phosphatase system have different lipid requirements, the activity of the former protein depending mainly on phosphatidylethanolamine and phosphatidylserine and that of the catalytic protein depending on phosphatidylcholine. In deoxycholate-disrupted liver microsomes (in which both the glucose-6-phosphatase activity and the phosphatidylcholine content are much higher than in hepatoma microsomes) incubation with phosphatidylcholine and lipid-exchange proteins alters neither the phospholipid composition nor the enzyme activity. THis suggests that the diminished activity of glucose-6-phosphatase in hepatomas may be partly due to a low level of phosphatidylcholine.", "contents": "Use of protein-mediated lipid exchange in the study of membrane-bound enzymes. The lipid dependence of glucose-6-phosphatase. The ability of liver lipid-exchange proteins to introduce foreign phospholipids into microsomes was used in a study of the lipid dependence of glucose-6-phosphatase. Supplementation of intact rat liver and hepatoma microsomes with exogeneous aminophospholipids prevents the decline of glucose-6-phosphatase activity during incubation, whereas the introduction of exogeneous phosphatidylcholine has no protective effect. On the contrary with deoxycholate-disrupted hepatoma microsomes, introduction of additional phosphatidylcholine causes activation while phosphatidylethanolamine has only little effect. The results are explained by assuming that the transport unit and the catalytic moiety of the glucose-6-phosphatase system have different lipid requirements, the activity of the former protein depending mainly on phosphatidylethanolamine and phosphatidylserine and that of the catalytic protein depending on phosphatidylcholine. In deoxycholate-disrupted liver microsomes (in which both the glucose-6-phosphatase activity and the phosphatidylcholine content are much higher than in hepatoma microsomes) incubation with phosphatidylcholine and lipid-exchange proteins alters neither the phospholipid composition nor the enzyme activity. THis suggests that the diminished activity of glucose-6-phosphatase in hepatomas may be partly due to a low level of phosphatidylcholine."}
{"id": "PMID:227689", "title": "Tubulin-associated nucleoside diphosphokinase.", "content": "Microtubule protein, prepared by cycles of polymerisation and dissociation, contained a nucleoside diphosphokinase (NDP kinase) activity (EC 2.7.4.6). This activity was not intrinsic to the tubulin dimer or the so-called microtubule-associated proteins. The NDP kinase had the following properties. (1) The enzyme existed in a low-molecular-weight form and in association with the complex of microtubule-associated proteins and tubulin (i.e. multimeric tubulin). (2) The low-molecular-weight species was also formed by dissociation of multimeric tubulin by salt or by removal of microtubule-associated proteins on phosphocellulose. (3) GDP bound to the exchangeable site of multimeric tubulin and also GDP derived from the E site of the tubulin dimer was a substrate for the NDP kinase. (4) The NDP kinase showed a 7-fold increase in activity during ATP-dependent microtubule assembly. On the basis of these properties, it is proposed that microtubule protein contains an NDP kinase specifically associated with tubulin and its functions.", "contents": "Tubulin-associated nucleoside diphosphokinase. Microtubule protein, prepared by cycles of polymerisation and dissociation, contained a nucleoside diphosphokinase (NDP kinase) activity (EC 2.7.4.6). This activity was not intrinsic to the tubulin dimer or the so-called microtubule-associated proteins. The NDP kinase had the following properties. (1) The enzyme existed in a low-molecular-weight form and in association with the complex of microtubule-associated proteins and tubulin (i.e. multimeric tubulin). (2) The low-molecular-weight species was also formed by dissociation of multimeric tubulin by salt or by removal of microtubule-associated proteins on phosphocellulose. (3) GDP bound to the exchangeable site of multimeric tubulin and also GDP derived from the E site of the tubulin dimer was a substrate for the NDP kinase. (4) The NDP kinase showed a 7-fold increase in activity during ATP-dependent microtubule assembly. On the basis of these properties, it is proposed that microtubule protein contains an NDP kinase specifically associated with tubulin and its functions."}
{"id": "PMID:227690", "title": "Uptake of 131I-19-cholesterol by normal and spontaneously hyperfunctioning canine adrenals.", "content": "In six normal dogs the adrenals could be visualized as separate areas of radioactivity at 7--10 days after injection of 20--40 muCi 131I-iodocholesterol per kg of body weight. Image analysis revealed uptake values of 0.15--0.3% of the injected dose. In five dogs with pituitary-dependent hyperadrenocorticism the adrenals became visible at 3--5 days after injection of the radiopharmaceutical, with uptake values of 0.38--2.2%. In six dogs with hyperadrenocorticism due to adrenocortical tumor the scintigraphy contributed to the diagnosis and the presurgical localization. The uptake values were within the normal range; the tumor could be observed at 3--10 days after injection. Additional findings on adrenal asymmetry and a case of fluctuating pituitary-dependent hyperadrenocorticism are discussed.", "contents": "Uptake of 131I-19-cholesterol by normal and spontaneously hyperfunctioning canine adrenals. In six normal dogs the adrenals could be visualized as separate areas of radioactivity at 7--10 days after injection of 20--40 muCi 131I-iodocholesterol per kg of body weight. Image analysis revealed uptake values of 0.15--0.3% of the injected dose. In five dogs with pituitary-dependent hyperadrenocorticism the adrenals became visible at 3--5 days after injection of the radiopharmaceutical, with uptake values of 0.38--2.2%. In six dogs with hyperadrenocorticism due to adrenocortical tumor the scintigraphy contributed to the diagnosis and the presurgical localization. The uptake values were within the normal range; the tumor could be observed at 3--10 days after injection. Additional findings on adrenal asymmetry and a case of fluctuating pituitary-dependent hyperadrenocorticism are discussed."}
{"id": "PMID:227692", "title": "The sensitivity of scintigraphic myocardial imaging by the use of 99mTc-labelled pyrophosphate in the diagnosis of cardiomyopathy of various etiology.", "content": "A total of 10 patients were examined. In five children who suffered from secondary cardiomyopathy accompanying progressive muscular dystrophy scintigraphic examination of the myocardium was made using 99mTc-labelled pyrophosphate. In two cases the scan was distinctly positive, in three cases negative. Five men with poorly defined primary nonobstructive cardiomyopathy were examined too. The scan was positive in three cases and negative in two cases. The positivity of the pyrophosphate scan of the heart is therefore not pathonomonic of ischaemic damage. An increased accumulation of pyrophosphate in the myocardium in cardiomyopathy indicates an acute phase of the disease.", "contents": "The sensitivity of scintigraphic myocardial imaging by the use of 99mTc-labelled pyrophosphate in the diagnosis of cardiomyopathy of various etiology. A total of 10 patients were examined. In five children who suffered from secondary cardiomyopathy accompanying progressive muscular dystrophy scintigraphic examination of the myocardium was made using 99mTc-labelled pyrophosphate. In two cases the scan was distinctly positive, in three cases negative. Five men with poorly defined primary nonobstructive cardiomyopathy were examined too. The scan was positive in three cases and negative in two cases. The positivity of the pyrophosphate scan of the heart is therefore not pathonomonic of ischaemic damage. An increased accumulation of pyrophosphate in the myocardium in cardiomyopathy indicates an acute phase of the disease."}
{"id": "PMID:227693", "title": "The particular usefulness of radioisotope methods in some benign bone diseases.", "content": "The authors have performed radioisotope examinations in 271 patients with various non-neoplastic bone diseases. According to their opinion, early diagnosis and follow-up of therapeutic results are the main characteristics which allow radioisotopes to play an important and irreplaceable role. They particularly emphasize the usefulness of radioisotope methods in femoral aseptic necrosis and Paget's disease.", "contents": "The particular usefulness of radioisotope methods in some benign bone diseases. The authors have performed radioisotope examinations in 271 patients with various non-neoplastic bone diseases. According to their opinion, early diagnosis and follow-up of therapeutic results are the main characteristics which allow radioisotopes to play an important and irreplaceable role. They particularly emphasize the usefulness of radioisotope methods in femoral aseptic necrosis and Paget's disease."}
{"id": "PMID:227694", "title": "HDL- and LDL-cholesterol in normal weight healthy children 13 years of age.", "content": "From 108 healthy 13 years old school children who took part on a longitudinal study in regard to serum lipids and lipoproteins 64 with normal body weight were examined. Lipoproteins were estimated by means of preparative ultracentrifuge and polyanionprecipitation (Heparin and Manganese-chloride) according to the Lipid Research Clinics Methods, NIH, Bethesda. Mean values and S.D. were calculated as: Total cholesterol: 155 +/- 29, 150 +/- 35 mg/dl; LDL-cholesterol 98 +/- 21 and 96 +/- 34 mg/dl; HDL-cholesterol 44 +/- 13 and 44 +/- 13 mg/dl for males and females respectively. The few data from the literature showing wide variations in LDL- and HDL-cholesterol concentrations are compared with our results; methodological considerations indicate that for further epidemiological studies concerning the possible risk factors for premature atherosclerosis standaradized laboratory tests should be provided.", "contents": "HDL- and LDL-cholesterol in normal weight healthy children 13 years of age. From 108 healthy 13 years old school children who took part on a longitudinal study in regard to serum lipids and lipoproteins 64 with normal body weight were examined. Lipoproteins were estimated by means of preparative ultracentrifuge and polyanionprecipitation (Heparin and Manganese-chloride) according to the Lipid Research Clinics Methods, NIH, Bethesda. Mean values and S.D. were calculated as: Total cholesterol: 155 +/- 29, 150 +/- 35 mg/dl; LDL-cholesterol 98 +/- 21 and 96 +/- 34 mg/dl; HDL-cholesterol 44 +/- 13 and 44 +/- 13 mg/dl for males and females respectively. The few data from the literature showing wide variations in LDL- and HDL-cholesterol concentrations are compared with our results; methodological considerations indicate that for further epidemiological studies concerning the possible risk factors for premature atherosclerosis standaradized laboratory tests should be provided."}
{"id": "PMID:227697", "title": "Effects of alkanols and halothane on rat brain muscarinic and alpha-adrenergic receptors.", "content": "Effects of the primary alcohols ethanol, butanol, pentanol and of halothane were measured on the binding functions of muscarinic and alpha-adrenergic receptor preparations in rat brain homogenates, with the use of the antagonists 3H-quinuclidinyl benzilate and 3H-WB-4101. IC50 concentrations of the alkanols for the muscarinic and alpha-receptors respectively were: ethanol, 2.0 M and 1.4 M; butanol, 0.24 M and 0.16 M; heptanol, 3.7 X 10(-3) M and 2.6 X 10(-3) M. The plot of IC50 values versus number of carbon atoms in the alkanol was linear and of the same slope as the plot of membrane fluidity changes, thus indicating the importance of the membrane/water partition coefficient of the alkanol. Halothane at clinical concentrations had no effect on the receptors, although significant inhibition of radioligand binding was produced by 2.5 mM halothane, and inhibition was complete in presence of 17.5 mM anesthetic. From the correlation of receptor binding inhibitions with membrane fluidity changes reported by other workers, it is suggested that the activity of membrane receptors may be modulated by the fluidity of their membranes.", "contents": "Effects of alkanols and halothane on rat brain muscarinic and alpha-adrenergic receptors. Effects of the primary alcohols ethanol, butanol, pentanol and of halothane were measured on the binding functions of muscarinic and alpha-adrenergic receptor preparations in rat brain homogenates, with the use of the antagonists 3H-quinuclidinyl benzilate and 3H-WB-4101. IC50 concentrations of the alkanols for the muscarinic and alpha-receptors respectively were: ethanol, 2.0 M and 1.4 M; butanol, 0.24 M and 0.16 M; heptanol, 3.7 X 10(-3) M and 2.6 X 10(-3) M. The plot of IC50 values versus number of carbon atoms in the alkanol was linear and of the same slope as the plot of membrane fluidity changes, thus indicating the importance of the membrane/water partition coefficient of the alkanol. Halothane at clinical concentrations had no effect on the receptors, although significant inhibition of radioligand binding was produced by 2.5 mM halothane, and inhibition was complete in presence of 17.5 mM anesthetic. From the correlation of receptor binding inhibitions with membrane fluidity changes reported by other workers, it is suggested that the activity of membrane receptors may be modulated by the fluidity of their membranes."}
{"id": "PMID:227709", "title": "Heterosynaptic postactivation potentiation in hippocampal CA 3 neurons: long-term changes of the postsynaptic potentials.", "content": "CA 3 neurons were excited synaptically by stimulation in the dentate hilus and the stratum radiatum of CA 1 in guinea pig hippocampal slices. Following repetitive stimulation (10--20 c/s, 10 s) of either stimulation site, the amplitudes of orthodromic population spikes or the probability of unitary discharges increased. Changes of the intracellularly recorded potentials were either (a) increased EPSP amplitudes associated with decreased IPSP amplitudes, or (b) increased IPSP amplitudes. A cell showing enhanced IPSPs after repetitive activation could respond with increased EPSP amplitudes and decreased IPSP amplitudes upon further repetitive activation. The potentiation, which was always preceded by a 5--10 min depression, lasted up to 3 h. This potentiation was heterosynaptic, since the responses to the non-stimulated input also changed and since the inputs were found to excite the pyramidal cells through separate synapses in double shock experiments. The heterosynaptic mode of the potentiation as well as the changes of the IPSPs indicate that not only the excitatory pathway but also the inhibitory pathway must be considered in explaining postactivation potentiation in this hippocampal field.", "contents": "Heterosynaptic postactivation potentiation in hippocampal CA 3 neurons: long-term changes of the postsynaptic potentials. CA 3 neurons were excited synaptically by stimulation in the dentate hilus and the stratum radiatum of CA 1 in guinea pig hippocampal slices. Following repetitive stimulation (10--20 c/s, 10 s) of either stimulation site, the amplitudes of orthodromic population spikes or the probability of unitary discharges increased. Changes of the intracellularly recorded potentials were either (a) increased EPSP amplitudes associated with decreased IPSP amplitudes, or (b) increased IPSP amplitudes. A cell showing enhanced IPSPs after repetitive activation could respond with increased EPSP amplitudes and decreased IPSP amplitudes upon further repetitive activation. The potentiation, which was always preceded by a 5--10 min depression, lasted up to 3 h. This potentiation was heterosynaptic, since the responses to the non-stimulated input also changed and since the inputs were found to excite the pyramidal cells through separate synapses in double shock experiments. The heterosynaptic mode of the potentiation as well as the changes of the IPSPs indicate that not only the excitatory pathway but also the inhibitory pathway must be considered in explaining postactivation potentiation in this hippocampal field."}
{"id": "PMID:227710", "title": "Biochemical compartmentation of fish tissues. II. Nonspecific phosphomonoesterases in brain.", "content": "The specific activities of acid and alkaline phosphatases in different regions of the brain of 9 nutritionally important fishes were worked out. The region consisting of pituitary, hypothalamus and thalamus showed the highest acid and alkaline phosphatase activities. Least activities of both the enzymes were found in the cerebellum and medulla oblongata. The piscivorous fishes contain the highest acid and alkaline phosphatase activity followed by cat fishes and major carps. The distributional pattern of these 2 enzymes in 4 regions of the brain of 9 fishes is the same.", "contents": "Biochemical compartmentation of fish tissues. II. Nonspecific phosphomonoesterases in brain. The specific activities of acid and alkaline phosphatases in different regions of the brain of 9 nutritionally important fishes were worked out. The region consisting of pituitary, hypothalamus and thalamus showed the highest acid and alkaline phosphatase activities. Least activities of both the enzymes were found in the cerebellum and medulla oblongata. The piscivorous fishes contain the highest acid and alkaline phosphatase activity followed by cat fishes and major carps. The distributional pattern of these 2 enzymes in 4 regions of the brain of 9 fishes is the same."}
{"id": "PMID:227711", "title": "The influence of insulin, cAMP and the calcium ionophore X 537 A on the growth of the cartilage analagen of limb buds in vitro.", "content": "Limb buds of 11-day-old mouse embryos were cultured for 6 days with insulin, dibutyryl cAMP and X 537 A. The cartilage anlage was reduced by insulin and enlarged by dibutyryl cAMP and X 537 A. The effects are due to changes in the amount of intercellular substance.", "contents": "The influence of insulin, cAMP and the calcium ionophore X 537 A on the growth of the cartilage analagen of limb buds in vitro. Limb buds of 11-day-old mouse embryos were cultured for 6 days with insulin, dibutyryl cAMP and X 537 A. The cartilage anlage was reduced by insulin and enlarged by dibutyryl cAMP and X 537 A. The effects are due to changes in the amount of intercellular substance."}
{"id": "PMID:227712", "title": "Globin gene expression in MSV-transformed fibroblasts.", "content": "The activation of globin gene expression on viral transformation of 3T3 cells was investigated. Globin mRNA was determined using a radioactive complementary DNA probe. No difference was found between 3T3 and transformed 3T3 cells. There does not therefore appear to be a random activation of extensive regions of the cellular genome.", "contents": "Globin gene expression in MSV-transformed fibroblasts. The activation of globin gene expression on viral transformation of 3T3 cells was investigated. Globin mRNA was determined using a radioactive complementary DNA probe. No difference was found between 3T3 and transformed 3T3 cells. There does not therefore appear to be a random activation of extensive regions of the cellular genome."}
{"id": "PMID:227713", "title": "Penicillin-induced formation of ribonuclease in rice (Oryza sativa L.) endosperm and its inhibition by abscisic acid.", "content": "Penicillin stimulates the formation of ribonuclease in embryoless rice (Oryza sativa L.) endosperm and enhances gibberelin-induced response. Penicillin-induced RNase production is completely inhibited by abscisic acid.", "contents": "Penicillin-induced formation of ribonuclease in rice (Oryza sativa L.) endosperm and its inhibition by abscisic acid. Penicillin stimulates the formation of ribonuclease in embryoless rice (Oryza sativa L.) endosperm and enhances gibberelin-induced response. Penicillin-induced RNase production is completely inhibited by abscisic acid."}
{"id": "PMID:227714", "title": "Correlation of immunogenicity with suppression of lymphocyte adenosine 3',5'-monophosphate-dependent protein kinase.", "content": "Cyclic-AMP-dependent protein kinase activity was depressed in whole spleen as well as in isolated splenic lymphocytes from 3-methylcholanthrene (MCA), R3230 AdCa mammary adenocarcinoma, N-hydroxy-2-acetylaminofluorene, and 4-dimethylaminoazobenzene (DMAAB) tumor-bearing Fischer rats as compared to control animals. The magnitude of depression increased with the immunogenicity of the tumor. The depressed enzyme activity was the result of a reduced Vmax for adenosine 3',5'-monophosphate (cAMP)-stimulated histone phosphorylation.", "contents": "Correlation of immunogenicity with suppression of lymphocyte adenosine 3',5'-monophosphate-dependent protein kinase. Cyclic-AMP-dependent protein kinase activity was depressed in whole spleen as well as in isolated splenic lymphocytes from 3-methylcholanthrene (MCA), R3230 AdCa mammary adenocarcinoma, N-hydroxy-2-acetylaminofluorene, and 4-dimethylaminoazobenzene (DMAAB) tumor-bearing Fischer rats as compared to control animals. The magnitude of depression increased with the immunogenicity of the tumor. The depressed enzyme activity was the result of a reduced Vmax for adenosine 3',5'-monophosphate (cAMP)-stimulated histone phosphorylation."}
{"id": "PMID:227715", "title": "Adrenergic reinnervation of the denervated rat urinary bladder.", "content": "In rats undergoing unilateral extirpation of the pelvic ganglion, the adrenergic innervation disappeared on the ipsilateral side of the urinary bladder. It had reappeared after 6--9 weeks.", "contents": "Adrenergic reinnervation of the denervated rat urinary bladder. In rats undergoing unilateral extirpation of the pelvic ganglion, the adrenergic innervation disappeared on the ipsilateral side of the urinary bladder. It had reappeared after 6--9 weeks."}
{"id": "PMID:227716", "title": "In vivo inhibition of the tyrosinase of hamster melanoma with sodium diethyldithiocarbamate.", "content": "In vivo inhibition of the DOPA-oxydase activity of the soluble tyrosinase fraction of melanotic hamster melanoma is found after i.p. administration of diethyldithiocarbamate, with considerable increase in the content of SH-groups which probably play the role of free radical scavengers.", "contents": "In vivo inhibition of the tyrosinase of hamster melanoma with sodium diethyldithiocarbamate. In vivo inhibition of the DOPA-oxydase activity of the soluble tyrosinase fraction of melanotic hamster melanoma is found after i.p. administration of diethyldithiocarbamate, with considerable increase in the content of SH-groups which probably play the role of free radical scavengers."}
{"id": "PMID:227717", "title": "TSH-receptor antibodies, HLA B8 and thyroid autoantibodies in patients with Graves' disease in therapeutically induced euthyroidism.", "content": "The prevalence of TSH-receptor antibodies and of thyroid autoantibodies was studied in 48 HLA-typed patients with Graves' disease, who were in an euthyroid state after antithyroid therapy with methimazole. TSH-receptor antibodies, which were found in 35% of the patients, did not correlate with the positivity of HLA B8. By contrast the persistence of thyroid microsomal antibodies was significantly associated with HLA B8.", "contents": "TSH-receptor antibodies, HLA B8 and thyroid autoantibodies in patients with Graves' disease in therapeutically induced euthyroidism. The prevalence of TSH-receptor antibodies and of thyroid autoantibodies was studied in 48 HLA-typed patients with Graves' disease, who were in an euthyroid state after antithyroid therapy with methimazole. TSH-receptor antibodies, which were found in 35% of the patients, did not correlate with the positivity of HLA B8. By contrast the persistence of thyroid microsomal antibodies was significantly associated with HLA B8."}
{"id": "PMID:227718", "title": "Leydig cell function in streptozotocin-induced diabetic rats.", "content": "Streptozotocin diabetic rats were infertile as a result of decreased Leydig cell function of the testes. The major changes found were: decreased number of Leydig cells and their spontaneous secretion of testosterone. No change in the receptors to LH on the Leydig cells was observed. LH was found to be obligatory for the regulation of Leydig cell function and fertility.", "contents": "Leydig cell function in streptozotocin-induced diabetic rats. Streptozotocin diabetic rats were infertile as a result of decreased Leydig cell function of the testes. The major changes found were: decreased number of Leydig cells and their spontaneous secretion of testosterone. No change in the receptors to LH on the Leydig cells was observed. LH was found to be obligatory for the regulation of Leydig cell function and fertility."}
{"id": "PMID:227752", "title": "Role of lipoprotein lipase in plasma triglyceride removal.", "content": "Intravenous injections of anti-lipoprotein lipase serunis quantitatively block the catabolism of very low density lipoprotein (VLDL) and portomicron triglyceride and specifically inhibit triglyceride transport into ovarian follicles. The immunological studies presented provide information on the site of action of lipoprotein lipase (LPL). In the anti-LPL serum-treated animals initial plasma triglyceride accumulation occurs at the time of antiserum injection. This instantaneous inhibition of triglyceride removal provides direct evidence that the functional LPL responsible for VLDL and portomicron triglyceride hydrolysis is located in sites within the plasma compartment readily accessible to immunoglobulins. In vitro immunological studies show that the adipose, heart, ovarian, and liver LPL share common immunological determinants. Biochemical studies on highly purified heart and adipose LPL suggest that these enzymes have identical protein moieties.", "contents": "Role of lipoprotein lipase in plasma triglyceride removal. Intravenous injections of anti-lipoprotein lipase serunis quantitatively block the catabolism of very low density lipoprotein (VLDL) and portomicron triglyceride and specifically inhibit triglyceride transport into ovarian follicles. The immunological studies presented provide information on the site of action of lipoprotein lipase (LPL). In the anti-LPL serum-treated animals initial plasma triglyceride accumulation occurs at the time of antiserum injection. This instantaneous inhibition of triglyceride removal provides direct evidence that the functional LPL responsible for VLDL and portomicron triglyceride hydrolysis is located in sites within the plasma compartment readily accessible to immunoglobulins. In vitro immunological studies show that the adipose, heart, ovarian, and liver LPL share common immunological determinants. Biochemical studies on highly purified heart and adipose LPL suggest that these enzymes have identical protein moieties."}
{"id": "PMID:227754", "title": "The partial adrenocortical hydroxylase deficiency syndrome in infertile women.", "content": "Eighteen infertile women desiring conception were selected for additional diagnostic studies on the basis of clinical evidence of hyperandrogenism characterized by acne and/or facial hirsutism. These 18 patients underwent stimulation tests with adrenocorticotropic hormone which demonstrated the presence of partial adrenocortical hydroxylase deficiences. All patients were then placed on glucocorticoid suppression therapy. Ten patients conceived and, of these, six required no therapy other than prednisone. Four conceived using a combination of prednisone and clomiphene therapy. Of othe eight patients who did not conceive, seven had other significant infertility factors. Therefore, of the patients without other significant fertility factors, 91% conceived. This study demonstrates that partial adrenocortical enzyme defects play a significant role in some women with clinical evidence of hyperandrogenism, and, in such women, either glococorticoid therapy alone or in combination with clomiphene is indicated.", "contents": "The partial adrenocortical hydroxylase deficiency syndrome in infertile women. Eighteen infertile women desiring conception were selected for additional diagnostic studies on the basis of clinical evidence of hyperandrogenism characterized by acne and/or facial hirsutism. These 18 patients underwent stimulation tests with adrenocorticotropic hormone which demonstrated the presence of partial adrenocortical hydroxylase deficiences. All patients were then placed on glucocorticoid suppression therapy. Ten patients conceived and, of these, six required no therapy other than prednisone. Four conceived using a combination of prednisone and clomiphene therapy. Of othe eight patients who did not conceive, seven had other significant infertility factors. Therefore, of the patients without other significant fertility factors, 91% conceived. This study demonstrates that partial adrenocortical enzyme defects play a significant role in some women with clinical evidence of hyperandrogenism, and, in such women, either glococorticoid therapy alone or in combination with clomiphene is indicated."}
{"id": "PMID:227755", "title": "The effect of factors causing induction of DNA breaks on transfection of chicken cells by the XC DNA, and the kinetics of appearance of virus-producing cells after transfection.", "content": "The effect of BUdR and 4NQO treatment of the recipient chicken fibroblast cultures on the efficiency of transfection by the XC DNA was investigated. The efficiency of transfection was 2-fold higher when the recipient cultures were incubated in the presence of 10 micrograms BUdR/ml in medium 199 (48%) than when cultures were not treated (25%). The efficiency was not further increased by exposure of BUdR-treated cultures to visible light for 20 min (31%). Growth of BUdR-treated cultures decreased after light irradiation which indicated that BUdR was incorporated into the host cell DNA. Treatment of the recipient cultures with 4NGO at a concentration of 0.4 micrograms/ml for 2 h before transfection exerted only unfavourable effects on transfection efficiency. In cultures positive in transfection, transformation was first detected 3 days after exposure to DNA by the infectious centre assay, with a frequency of 4.76 +/- 6.46 transformed cells per 10(6) cells.", "contents": "The effect of factors causing induction of DNA breaks on transfection of chicken cells by the XC DNA, and the kinetics of appearance of virus-producing cells after transfection. The effect of BUdR and 4NQO treatment of the recipient chicken fibroblast cultures on the efficiency of transfection by the XC DNA was investigated. The efficiency of transfection was 2-fold higher when the recipient cultures were incubated in the presence of 10 micrograms BUdR/ml in medium 199 (48%) than when cultures were not treated (25%). The efficiency was not further increased by exposure of BUdR-treated cultures to visible light for 20 min (31%). Growth of BUdR-treated cultures decreased after light irradiation which indicated that BUdR was incorporated into the host cell DNA. Treatment of the recipient cultures with 4NGO at a concentration of 0.4 micrograms/ml for 2 h before transfection exerted only unfavourable effects on transfection efficiency. In cultures positive in transfection, transformation was first detected 3 days after exposure to DNA by the infectious centre assay, with a frequency of 4.76 +/- 6.46 transformed cells per 10(6) cells."}
{"id": "PMID:227758", "title": "[Studies on the heterogeneity of urinary HCG molecules by RRA and RIA (author's transl)].", "content": "A sensitive bioassay (Radio receptor assay: RRA) for urinary hCG which is independent of plasma half life and metabolism has been developed by utilizing the specific binding of 125I-hCG to 150 approximately 2000g fraction of homogenates of the rat testis. The receptor and immunological activity (RRA/RIA) ratio of urinary hCG in pregnant and trophoblastic diseased women was examined. In addition, the urine of women with normal pregnancies was studied for quantitative and qualitative differences among hCG molecules, by gel filtration on a Sephadex G-100, and each fraction was measured by RRA and radioimmunoassay (RIA). 1) The sensitivity of RRA was 4 ng/ml with a precision (lambda) of 0.03. The intraassay coefficient of variation and that for inter assay were 2 approximately 10% and 12.1% respectively. There was a complete lack of cross reaction with PRL, hCG alpha, hCG beta, and FSH; this indicated a high specificity of the RRA. 2) Receptor reactive hCG in urine throughout pregnancy showed a major peak in the 10th week and declined, but remained fairly constant until the 31st week of pregnancy. The RRA/RIA ratio in urinary hCG of normal pregnancies was highest in the first trimester and lower in the second and third trimester. The average value throughout gestation was 2.04 +/- 0.18 (SE), which was about 2 times greater than that (1.08 +/0 0.11(SE)) of trophoblastic diseases (p less than 0.01). 3) The RRA/RIA ratio in the patients with trophoblastic tumors was highest in the hydatidiform mole and lowest in the chorioepithelioma. 4) When the urine of normal pregnancies was gel filtrated on a Sephadex G-100, it was found that receptor active molecules of hCG were present in urine of the first and second trimester. These results indicated that the RRA/RIA ratio in urinary hCG was distinct in normal pregnancies from trophoblastic tumors and would contribute sufficiently to an early diagnosis and the treatment of successive trophoblastic disease in follow-ups of patients with hydatidiform mole.", "contents": "[Studies on the heterogeneity of urinary HCG molecules by RRA and RIA (author's transl)]. A sensitive bioassay (Radio receptor assay: RRA) for urinary hCG which is independent of plasma half life and metabolism has been developed by utilizing the specific binding of 125I-hCG to 150 approximately 2000g fraction of homogenates of the rat testis. The receptor and immunological activity (RRA/RIA) ratio of urinary hCG in pregnant and trophoblastic diseased women was examined. In addition, the urine of women with normal pregnancies was studied for quantitative and qualitative differences among hCG molecules, by gel filtration on a Sephadex G-100, and each fraction was measured by RRA and radioimmunoassay (RIA). 1) The sensitivity of RRA was 4 ng/ml with a precision (lambda) of 0.03. The intraassay coefficient of variation and that for inter assay were 2 approximately 10% and 12.1% respectively. There was a complete lack of cross reaction with PRL, hCG alpha, hCG beta, and FSH; this indicated a high specificity of the RRA. 2) Receptor reactive hCG in urine throughout pregnancy showed a major peak in the 10th week and declined, but remained fairly constant until the 31st week of pregnancy. The RRA/RIA ratio in urinary hCG of normal pregnancies was highest in the first trimester and lower in the second and third trimester. The average value throughout gestation was 2.04 +/- 0.18 (SE), which was about 2 times greater than that (1.08 +/0 0.11(SE)) of trophoblastic diseases (p less than 0.01). 3) The RRA/RIA ratio in the patients with trophoblastic tumors was highest in the hydatidiform mole and lowest in the chorioepithelioma. 4) When the urine of normal pregnancies was gel filtrated on a Sephadex G-100, it was found that receptor active molecules of hCG were present in urine of the first and second trimester. These results indicated that the RRA/RIA ratio in urinary hCG was distinct in normal pregnancies from trophoblastic tumors and would contribute sufficiently to an early diagnosis and the treatment of successive trophoblastic disease in follow-ups of patients with hydatidiform mole."}
{"id": "PMID:227760", "title": "Localization of LH receptors on luteal cells with a ferritin--LH conjugate.", "content": "In order to study the distribution of LH (HCG) receptors on luteal cells ferritin was coupled to ovine LH with glutaraldehyde and purified by gel chromatography. The conjugate (FELH) competed with 125I-hCG for binding to isolated luteal membranes and stimulated a dose-dependent release of progesterone (P) from isolated luteal cells which was inhibited by PGF2 alpha. FELH was distributed as single molecules or in small clusters at intervals on the surfaces of luteal cells labeled at 37 degrees C, 4 degrees C or with formaldehyde prefixation. Capping or preferential labeling at one site was not observed. The general distribution of LH (hCG) binding sites at 37 degrees C was confirmed by light-microscopic autoradiography. The distribution at 4 degrees C or with prefixation was more diffuse than at 37 degrees C suggesting that FELH binding induces small changes in receptor aggregation. Binding of FELH was specific since excess hCG reduced FELH binding to luteal cells. In cells labeled at 4 degrees C, rinsed and warmed to 37 degrees C FELH was observed along cell surfaces and within some coated vesicles and a few lysosomes within minutes suggesting that receptor internalization is a rapid and possibly continual process.", "contents": "Localization of LH receptors on luteal cells with a ferritin--LH conjugate. In order to study the distribution of LH (HCG) receptors on luteal cells ferritin was coupled to ovine LH with glutaraldehyde and purified by gel chromatography. The conjugate (FELH) competed with 125I-hCG for binding to isolated luteal membranes and stimulated a dose-dependent release of progesterone (P) from isolated luteal cells which was inhibited by PGF2 alpha. FELH was distributed as single molecules or in small clusters at intervals on the surfaces of luteal cells labeled at 37 degrees C, 4 degrees C or with formaldehyde prefixation. Capping or preferential labeling at one site was not observed. The general distribution of LH (hCG) binding sites at 37 degrees C was confirmed by light-microscopic autoradiography. The distribution at 4 degrees C or with prefixation was more diffuse than at 37 degrees C suggesting that FELH binding induces small changes in receptor aggregation. Binding of FELH was specific since excess hCG reduced FELH binding to luteal cells. In cells labeled at 4 degrees C, rinsed and warmed to 37 degrees C FELH was observed along cell surfaces and within some coated vesicles and a few lysosomes within minutes suggesting that receptor internalization is a rapid and possibly continual process."}
{"id": "PMID:227761", "title": "The effect of induced hyperprolactinaemia on Leydig cell function and LH-induced loss of LH-receptors in the rat testis.", "content": "Anterior pituitary glands were transplanted beneath the kidney capsule of intact, adult male rats to induce hyperprolactinaemia. This resulted in reduced serum levels of LH and FSH and increased adrenal weight. In pituitary-transplanted rats, testicular hCG-receptor binding was increased by 55 to 175%, whilst the capacity of the testis to secrete testosterone in vitro was greatly reduced. Injection of ovine LH into control and pituitary-transplanted rats resulted in similar percentage reductions in hCG-receptor binding in the two groups. This treatment impaired the in vitro steroidogenic responsiveness of testes from control rats at 24 h after injection, but had no major effect on the already-impaired, steroidogenic responsiveness of testes from pituitary-transplanted rats. Although induction of hyperprolactinaemia resulted in marked changes in Leydig cell function, these alterations were possibly due to the chronically reduced serum gonadotrophin levels in hyperprolactinaemic rats as well as a direct effect of prolactin on the Leydig cell.", "contents": "The effect of induced hyperprolactinaemia on Leydig cell function and LH-induced loss of LH-receptors in the rat testis. Anterior pituitary glands were transplanted beneath the kidney capsule of intact, adult male rats to induce hyperprolactinaemia. This resulted in reduced serum levels of LH and FSH and increased adrenal weight. In pituitary-transplanted rats, testicular hCG-receptor binding was increased by 55 to 175%, whilst the capacity of the testis to secrete testosterone in vitro was greatly reduced. Injection of ovine LH into control and pituitary-transplanted rats resulted in similar percentage reductions in hCG-receptor binding in the two groups. This treatment impaired the in vitro steroidogenic responsiveness of testes from control rats at 24 h after injection, but had no major effect on the already-impaired, steroidogenic responsiveness of testes from pituitary-transplanted rats. Although induction of hyperprolactinaemia resulted in marked changes in Leydig cell function, these alterations were possibly due to the chronically reduced serum gonadotrophin levels in hyperprolactinaemic rats as well as a direct effect of prolactin on the Leydig cell."}
{"id": "PMID:227762", "title": "The effect of insulin and guanosine nucleotides on protein phosphorylations by sarcolemma membranes from skeletal muscle.", "content": "In a previous report we have shown that insulin increases the phosphorylation of an endogenous protein of mol. wt. 16 000 daltons in sarcolemma membranes. In the present work we have demonstrated that phosphorylations of exogenous histones by the sarcolemma membranes are also increased by insulin. These results indicate that insulin activates a cyclic-AMP-independent protein kinase in sarcolemma membranes. The stimulatory effect of insulin on protein phosphorylations is increased by GTP and its analogue GMP-P(NH)P. The insulin effect was increased 3--4-fold by micromolar concentrations of GTP. The effect by the analogue GMP-P(NH)P was somewhat less. In the absence of insulin guanosine nucleotides had no effect on phosphorylation of the proteins. The results suggest that GTP is a modulator in the activation of a sarcolemma membrane protein kinase by insulin.", "contents": "The effect of insulin and guanosine nucleotides on protein phosphorylations by sarcolemma membranes from skeletal muscle. In a previous report we have shown that insulin increases the phosphorylation of an endogenous protein of mol. wt. 16 000 daltons in sarcolemma membranes. In the present work we have demonstrated that phosphorylations of exogenous histones by the sarcolemma membranes are also increased by insulin. These results indicate that insulin activates a cyclic-AMP-independent protein kinase in sarcolemma membranes. The stimulatory effect of insulin on protein phosphorylations is increased by GTP and its analogue GMP-P(NH)P. The insulin effect was increased 3--4-fold by micromolar concentrations of GTP. The effect by the analogue GMP-P(NH)P was somewhat less. In the absence of insulin guanosine nucleotides had no effect on phosphorylation of the proteins. The results suggest that GTP is a modulator in the activation of a sarcolemma membrane protein kinase by insulin."}
{"id": "PMID:227764", "title": "Monoamine oxidase and catechol-O-methyltransferase activity in hamster and rat insulinomas.", "content": "Hamster and rat insulinomas were assayed for norepinephrine, dopamine and serotonin concentration and for monoamine oxidase and catechol-o-ethyltransferase (COMT) activity. The concentration of norepinephrine (mean 0.55 mumol/kg, range less than 0.20 to 2.64 mumol/kg) and serotonin (mean 5.22 mucol/kg, rang less than 0.6 to 26.5 mumol/kg) in hamster insulinomas were comparable to previously reported concentrations. Dopamine conentration (mean 0.34 mumol/kg, range less than 0.20 to 0.95 mumol/kg) was only 2 to 2.5% of that reported previously. Monoamine oxidase activity of the hamster and rat insulinomas were comparable to those of normal hamster islets. In contrast, the COMT activity of both insulinomas was much greater than the COMT activity of normal pancreatic islets of both species and was greater than in several other tissues and tumours. The tumour COMT, which was predominantly in the cytosol, was Mg2+ dependent and had a comparable sensitivity to inhibition by tropolone as purified beef-liver COMT. Hamster insulinoma monoamine oxidase was more sensitive than rat insulinoma monoamine oxidase to inhibition by tranylcypromine and deprenyl, while rat insulinoma monoamine oxidase was more sensitive to inhibition by clorgyline and was more heat labile.", "contents": "Monoamine oxidase and catechol-O-methyltransferase activity in hamster and rat insulinomas. Hamster and rat insulinomas were assayed for norepinephrine, dopamine and serotonin concentration and for monoamine oxidase and catechol-o-ethyltransferase (COMT) activity. The concentration of norepinephrine (mean 0.55 mumol/kg, range less than 0.20 to 2.64 mumol/kg) and serotonin (mean 5.22 mucol/kg, rang less than 0.6 to 26.5 mumol/kg) in hamster insulinomas were comparable to previously reported concentrations. Dopamine conentration (mean 0.34 mumol/kg, range less than 0.20 to 0.95 mumol/kg) was only 2 to 2.5% of that reported previously. Monoamine oxidase activity of the hamster and rat insulinomas were comparable to those of normal hamster islets. In contrast, the COMT activity of both insulinomas was much greater than the COMT activity of normal pancreatic islets of both species and was greater than in several other tissues and tumours. The tumour COMT, which was predominantly in the cytosol, was Mg2+ dependent and had a comparable sensitivity to inhibition by tropolone as purified beef-liver COMT. Hamster insulinoma monoamine oxidase was more sensitive than rat insulinoma monoamine oxidase to inhibition by tranylcypromine and deprenyl, while rat insulinoma monoamine oxidase was more sensitive to inhibition by clorgyline and was more heat labile."}
{"id": "PMID:227770", "title": "The use of the psychiatric consultation record for residency training.", "content": "The Psychiatric Consultation Record (PCR) is an instrument developed to aid in the teaching of consultation psychiatry, to evaluate the impact of this teaching, and to provide an overall assessment of the consultation training program at St. Luke's Hospital. The PCR both structures the resident's training experience and provides a tool with which he or she can integrate theoretical and practical knowledge pertaining to consultation work. Its use has enabled supervisors to detect the degree to which didactic material has become integrated into residents' thinking and has provided data through which the scope and quality of each resident's work can be rapidly assessed. Finally, its use has brought to light deficiencies in service delivery which, before the use of this instrument, had not been apparent.", "contents": "The use of the psychiatric consultation record for residency training. The Psychiatric Consultation Record (PCR) is an instrument developed to aid in the teaching of consultation psychiatry, to evaluate the impact of this teaching, and to provide an overall assessment of the consultation training program at St. Luke's Hospital. The PCR both structures the resident's training experience and provides a tool with which he or she can integrate theoretical and practical knowledge pertaining to consultation work. Its use has enabled supervisors to detect the degree to which didactic material has become integrated into residents' thinking and has provided data through which the scope and quality of each resident's work can be rapidly assessed. Finally, its use has brought to light deficiencies in service delivery which, before the use of this instrument, had not been apparent."}
{"id": "PMID:227771", "title": "Cloning the argF gene from Escherichia coli K-12 with simian virus 40.", "content": "We have inserted a gene coding for ornithine transcarbamylase (OTCase) from Escherichia coli K-12 into the late gene region of simian virus 40 (SV40) DNA and propagated the hybrid molecules as free episomes or by co-infection with an SV40 tsA helper virus. In the first case, the E. coli argF gene was inserted via the EcoRI and BamHI termini in the late gene region of SV40 and the recombinant molecules were used to transfect monkey kidney cells. The hybrid DNA, which was too large to be encapsidated, was replicated for a short time (14 days) but was eventually lost from the surviving cells. In order to allow the argF gene to be packaged into virions, we purified two SV40 vectors containing large deletions of late gene region sequences. One was a 3325 base pair segment from a HaeII + BamHI digest. The argF gene was joined to both vectors at the BamHI site and these linear molecules were used to transfect monkey cells in the presence of SV40 tsA58 DNA as helper. These hybrid DNAs were replicated and packaged into virions. Late in the lytic infection of monkey cells, polyadenylated, cytoplasmic argF transcripts were detected, but significant translation of these trancripts was not observed.", "contents": "Cloning the argF gene from Escherichia coli K-12 with simian virus 40. We have inserted a gene coding for ornithine transcarbamylase (OTCase) from Escherichia coli K-12 into the late gene region of simian virus 40 (SV40) DNA and propagated the hybrid molecules as free episomes or by co-infection with an SV40 tsA helper virus. In the first case, the E. coli argF gene was inserted via the EcoRI and BamHI termini in the late gene region of SV40 and the recombinant molecules were used to transfect monkey kidney cells. The hybrid DNA, which was too large to be encapsidated, was replicated for a short time (14 days) but was eventually lost from the surviving cells. In order to allow the argF gene to be packaged into virions, we purified two SV40 vectors containing large deletions of late gene region sequences. One was a 3325 base pair segment from a HaeII + BamHI digest. The argF gene was joined to both vectors at the BamHI site and these linear molecules were used to transfect monkey cells in the presence of SV40 tsA58 DNA as helper. These hybrid DNAs were replicated and packaged into virions. Late in the lytic infection of monkey cells, polyadenylated, cytoplasmic argF transcripts were detected, but significant translation of these trancripts was not observed."}
{"id": "PMID:227776", "title": "Immunogenicity and bioactivity of glucagon, modified at methionine-27.", "content": "Porcine glucagon was modified at methionine-27 by methylation or oxidation. Antisera against the glucagon derivatives were obtained. One of these antisera showed a high affinity for glucagon, with no cross-reactivity with gut-GLI 1. Biological activities of these derivatives were assessed on rat hepatocytes. Both derivatives had the same maximal glucose-mobilising activity as native glucagon, but a decrease potency, suggesting a crucial role of methionine in the binding of glucagon to its hepatic receptor.", "contents": "Immunogenicity and bioactivity of glucagon, modified at methionine-27. Porcine glucagon was modified at methionine-27 by methylation or oxidation. Antisera against the glucagon derivatives were obtained. One of these antisera showed a high affinity for glucagon, with no cross-reactivity with gut-GLI 1. Biological activities of these derivatives were assessed on rat hepatocytes. Both derivatives had the same maximal glucose-mobilising activity as native glucagon, but a decrease potency, suggesting a crucial role of methionine in the binding of glucagon to its hepatic receptor."}
{"id": "PMID:227777", "title": "Hydrocortisone and vitamin D3 stimulation of 32Pi-phosphate accumulation by organ-cultured chick embryo duodenum.", "content": "Either vitamin D3 (or 1 alpha,25--(OH)2-D3) or hydrocortisone (HC) stimulated phosphate accumulation by organ-cultured embryonic chick duodenum. In combination, these two steroids stimulated phosphate uptake synergistically. Phosphate accumulation appeared to be independent of other vitamin D3-stimulated processes: CaBP concentration, cAMP concentration, or alkaline phosphatase activity. L-phenylalanine, a reported alkaline phosphatase inhibitor, when added to the culture medium progressively inhibited either D3- or HC-stimulated phosphate uptake subsequent to culture, but did not inhibit the synergistic action. Under these conditions L-phenylalanine had no consistent effect on alkaline phosphatase activity but unexpectedly, greatly inhibited vitamin D3-stimulated CaBP concentration, but only in the absence of HC. Some limited suggestion of an intestinal phosphoprotein sensitive to either vitamin D3 or HC was observed.", "contents": "Hydrocortisone and vitamin D3 stimulation of 32Pi-phosphate accumulation by organ-cultured chick embryo duodenum. Either vitamin D3 (or 1 alpha,25--(OH)2-D3) or hydrocortisone (HC) stimulated phosphate accumulation by organ-cultured embryonic chick duodenum. In combination, these two steroids stimulated phosphate uptake synergistically. Phosphate accumulation appeared to be independent of other vitamin D3-stimulated processes: CaBP concentration, cAMP concentration, or alkaline phosphatase activity. L-phenylalanine, a reported alkaline phosphatase inhibitor, when added to the culture medium progressively inhibited either D3- or HC-stimulated phosphate uptake subsequent to culture, but did not inhibit the synergistic action. Under these conditions L-phenylalanine had no consistent effect on alkaline phosphatase activity but unexpectedly, greatly inhibited vitamin D3-stimulated CaBP concentration, but only in the absence of HC. Some limited suggestion of an intestinal phosphoprotein sensitive to either vitamin D3 or HC was observed."}
{"id": "PMID:227778", "title": "Binding of somatomedin-A and -C, NSILA-S and insulin to human placental cell membranes.", "content": "Binding of labeled SM-A, SM-C, NSILA-S and insulin to human placental cell membranes was studied in trying to answer the question how many receptor populations were involved using one single organ system. The data suggest that all labeled SM-like substances bind to closely related if not identical receptor populations. The binding is reduced by very low concentrations of SM-like material and only by very high concentrations of insulin. In contrast, as already known from the literature, 125I-insulin binds mostly to a different receptor population, which is sensitive both to insulin and SM-like substances. Furthermore, the data indicate that 125I-SM-A and 125I-SM-C, in addition to binding to similar or identical receptors, also bind to separate receptor populations, suggesting that the labels are composed of more than one component.", "contents": "Binding of somatomedin-A and -C, NSILA-S and insulin to human placental cell membranes. Binding of labeled SM-A, SM-C, NSILA-S and insulin to human placental cell membranes was studied in trying to answer the question how many receptor populations were involved using one single organ system. The data suggest that all labeled SM-like substances bind to closely related if not identical receptor populations. The binding is reduced by very low concentrations of SM-like material and only by very high concentrations of insulin. In contrast, as already known from the literature, 125I-insulin binds mostly to a different receptor population, which is sensitive both to insulin and SM-like substances. Furthermore, the data indicate that 125I-SM-A and 125I-SM-C, in addition to binding to similar or identical receptors, also bind to separate receptor populations, suggesting that the labels are composed of more than one component."}
{"id": "PMID:227779", "title": "Studies on cytochrome c oxidase, V. Polypeptide IV: alignment and amino acid sequences on cyanogen bromide fragments.", "content": "The isolation and chemical characterization of polypeptide IV from beef heart cytochrome oxidase is described. The protein is one of the main (stoichiometric) components of the oxidase. It is the largest polypeptide of the enzyme synthezised in the cytoplasm and has, as such, also been identified in enzyme preparations from yeast and Neurospora. A partial sequence, consisting of 105 amino acid residues which give a frame work of the covalent structure of the polypeptide is obtained from N- anc C-terminal sequencing and from the cyanogen bromide fragments of the chain. The isolation and sequencing of the fragments of this membrane protein are discussed.", "contents": "Studies on cytochrome c oxidase, V. Polypeptide IV: alignment and amino acid sequences on cyanogen bromide fragments. The isolation and chemical characterization of polypeptide IV from beef heart cytochrome oxidase is described. The protein is one of the main (stoichiometric) components of the oxidase. It is the largest polypeptide of the enzyme synthezised in the cytoplasm and has, as such, also been identified in enzyme preparations from yeast and Neurospora. A partial sequence, consisting of 105 amino acid residues which give a frame work of the covalent structure of the polypeptide is obtained from N- anc C-terminal sequencing and from the cyanogen bromide fragments of the chain. The isolation and sequencing of the fragments of this membrane protein are discussed."}
{"id": "PMID:227780", "title": "Studies on cytochrome c oxidase, VI. Polypeptide IV. the complete primary structure.", "content": "The complete primary structure of the cytoplasmically synthesized polypeptide IV from beef heart cytochrome oxidase was determined via isolation and sequencing of overlapping methionine, tryptophan, and arginine fragments. The protein consists of 147 amino acids (Mr 17153). It is characterized as a part of a membrane protein complex by a hydrophobic segment consisting of 19 residues. It is suggested that this segment contacts the lipids of the inner mitochondiral membrane. Additional specific contacts may result from pairwise formation of salt bridges between ionic groups of the protein and the phospholipids. The function of this component of the terminal oxidase is yet unknown.", "contents": "Studies on cytochrome c oxidase, VI. Polypeptide IV. the complete primary structure. The complete primary structure of the cytoplasmically synthesized polypeptide IV from beef heart cytochrome oxidase was determined via isolation and sequencing of overlapping methionine, tryptophan, and arginine fragments. The protein consists of 147 amino acids (Mr 17153). It is characterized as a part of a membrane protein complex by a hydrophobic segment consisting of 19 residues. It is suggested that this segment contacts the lipids of the inner mitochondiral membrane. Additional specific contacts may result from pairwise formation of salt bridges between ionic groups of the protein and the phospholipids. The function of this component of the terminal oxidase is yet unknown."}
{"id": "PMID:227781", "title": "Opioid activity of delta O-endorphin in the guinea pig ileum.", "content": "The oligopeptides beta- and delta O-endorphin were isolated from porcine and bovine pituitary respectively. Their opiate activity was determined in the guinea pig ileum and compared to that of the pentapeptide methionine-enkephalin and morphine. The rank order of opioid activity was found to be: morphine greater than beta-endorphin = Met-enkephalin greater than delta O-Endorphin which lacks the four C-terminal amino acids of beta-endorphin displayed 60% of the activity of beta-endorphin. These results indicate, that C-terminal amino acids contribute little to the affinity of beta-endorphin for opiate receptors in the guinea pig ileum.", "contents": "Opioid activity of delta O-endorphin in the guinea pig ileum. The oligopeptides beta- and delta O-endorphin were isolated from porcine and bovine pituitary respectively. Their opiate activity was determined in the guinea pig ileum and compared to that of the pentapeptide methionine-enkephalin and morphine. The rank order of opioid activity was found to be: morphine greater than beta-endorphin = Met-enkephalin greater than delta O-Endorphin which lacks the four C-terminal amino acids of beta-endorphin displayed 60% of the activity of beta-endorphin. These results indicate, that C-terminal amino acids contribute little to the affinity of beta-endorphin for opiate receptors in the guinea pig ileum."}
{"id": "PMID:227782", "title": "[Serratia, cause of nosocomial infections and its occurrence in the patient's environment (author's transl)].", "content": "The Serratia infections are increasing in hospitalized patients, especially in those with reduced defences. This paper deals with a review of the recent literature on the microbiological characterization of the different Serratia species, the clinical syndrome associated with Serratia infections and the mode of transmission of this opportunistic pathogen. This author's experience in the occurrenceof Serratia in the hospital environment and their sensitivity to antibiotics and disinfectants is presented. The prevention of this infection stemps from these epidemiological data and, above all, consists in application of adequate hospital hygiene measures.", "contents": "[Serratia, cause of nosocomial infections and its occurrence in the patient's environment (author's transl)]. The Serratia infections are increasing in hospitalized patients, especially in those with reduced defences. This paper deals with a review of the recent literature on the microbiological characterization of the different Serratia species, the clinical syndrome associated with Serratia infections and the mode of transmission of this opportunistic pathogen. This author's experience in the occurrenceof Serratia in the hospital environment and their sensitivity to antibiotics and disinfectants is presented. The prevention of this infection stemps from these epidemiological data and, above all, consists in application of adequate hospital hygiene measures."}
{"id": "PMID:227784", "title": "The immunological generation of a platelet-activating factor and a platet-lytic factor in the rat.", "content": "Antigen challenge of the rat peritoneal cavity which had been prepared with IgGa-rich antiserum generated activities which released [14C]-serotonin from pre-labelled human platelets. After adsorption of these activities onto Amberlite XAD-8 and elution in 80% ethanol, two factors of differing polarity were resolved by chromatography on diethylaminoethyl cellulose in organic solvents. The activity eluting in the 7:1 chloroform:methanol solvent contained a platelet-lytic factor (PLF) assessed by the parallel release of lactic acid dehydrogenase and [14C]-serotonin; the cytotoxicity of this fraction was confirmed by phase-contrast microscopy examination which demonstrated fragmentation of the exposed platelets. The activity eluting in the 1:1 methanol: aqueous 1.0 M ammonium carbonate solvent was a platelet-activating factor (PAF) as defined by release of [14C]-serotonin without lactic acid dehydrogenase. Both the lytic and the activating principles were separable from slow reacting substance of anaphylaxis and polymorphonuclear leucocyte chemotactic activity, and each presented a single activity peak of differing mobility when chromatographed on silica gel H plates. Human eosinophil phospholipase D inactivated the lytic factor by more than 85% in 2 h at 37 degrees without affecting the activity of the activating factor. The release of [14C]-serotonin induced by the PAF was not affected by the absence of calcium from the medium or by elevations in the platelet concentrations of cyclic AMP or cyclic GMP that resulted from pre-incubation of platelets with prostaglandin D2 or sodium ascorbate, respectively.", "contents": "The immunological generation of a platelet-activating factor and a platet-lytic factor in the rat. Antigen challenge of the rat peritoneal cavity which had been prepared with IgGa-rich antiserum generated activities which released [14C]-serotonin from pre-labelled human platelets. After adsorption of these activities onto Amberlite XAD-8 and elution in 80% ethanol, two factors of differing polarity were resolved by chromatography on diethylaminoethyl cellulose in organic solvents. The activity eluting in the 7:1 chloroform:methanol solvent contained a platelet-lytic factor (PLF) assessed by the parallel release of lactic acid dehydrogenase and [14C]-serotonin; the cytotoxicity of this fraction was confirmed by phase-contrast microscopy examination which demonstrated fragmentation of the exposed platelets. The activity eluting in the 1:1 methanol: aqueous 1.0 M ammonium carbonate solvent was a platelet-activating factor (PAF) as defined by release of [14C]-serotonin without lactic acid dehydrogenase. Both the lytic and the activating principles were separable from slow reacting substance of anaphylaxis and polymorphonuclear leucocyte chemotactic activity, and each presented a single activity peak of differing mobility when chromatographed on silica gel H plates. Human eosinophil phospholipase D inactivated the lytic factor by more than 85% in 2 h at 37 degrees without affecting the activity of the activating factor. The release of [14C]-serotonin induced by the PAF was not affected by the absence of calcium from the medium or by elevations in the platelet concentrations of cyclic AMP or cyclic GMP that resulted from pre-incubation of platelets with prostaglandin D2 or sodium ascorbate, respectively."}
{"id": "PMID:227786", "title": "Cytomegalovirus isolation from a chimpanzee with acute demyelinating disease after inoculation of multiple sclerosis brain cells.", "content": "A strain of cytomegalovirus (CMV) was isolated during the third subcultivation of explants from the left frontal lobe of a chimpanzee that developed paralysis more than 3 years after intracerebral inoculation at birth with brain cell cultures derived from a patient with multiple sclerosis. Another strain of CMV was also isolated from a lymph node culture taken from the same chimp. The isolates, designated MZM-13 and MZM-14, produced a cytopathic effect characteristic for CMV when inoculated into brain, ganglion, or fibroblast cultures of human or simian origin. Infected cells contained characteristic Cowdry A intranuclear as well as intracytoplasmic inclusion bodies, and 100-nm spherical herpes-like virus particles were detected by electron microscopy in the nucleus and cytoplasm of infected cells. Virus was further identified as CMV with convalescent human anti-CMV serum. Complement-fixing antibody to CMV was present at a titer of 1:32 when the acutely ill chimpanzee was sacrificed. No antibody was detected at birth or at 1 or 2 years of age. A newborn chimpanzee inoculated intracerebrally with MZM-13 developed clinically asymptomatic lesions in the central nervous system characterized by acute and chronic inflammation and degeneration of myelin in cranial and spinal nerve roots. Restriction endonuclease analysis of viral deoxyribonucleic acid isolated from these two viruses indicated that MZM-13 and MZM-14 are identical and are closely related to chimpanzee CMV. No similarity in restriction endonuclease fragment patterns was found between MZM virus and the Towne and Clegg strains of human CMV.", "contents": "Cytomegalovirus isolation from a chimpanzee with acute demyelinating disease after inoculation of multiple sclerosis brain cells. A strain of cytomegalovirus (CMV) was isolated during the third subcultivation of explants from the left frontal lobe of a chimpanzee that developed paralysis more than 3 years after intracerebral inoculation at birth with brain cell cultures derived from a patient with multiple sclerosis. Another strain of CMV was also isolated from a lymph node culture taken from the same chimp. The isolates, designated MZM-13 and MZM-14, produced a cytopathic effect characteristic for CMV when inoculated into brain, ganglion, or fibroblast cultures of human or simian origin. Infected cells contained characteristic Cowdry A intranuclear as well as intracytoplasmic inclusion bodies, and 100-nm spherical herpes-like virus particles were detected by electron microscopy in the nucleus and cytoplasm of infected cells. Virus was further identified as CMV with convalescent human anti-CMV serum. Complement-fixing antibody to CMV was present at a titer of 1:32 when the acutely ill chimpanzee was sacrificed. No antibody was detected at birth or at 1 or 2 years of age. A newborn chimpanzee inoculated intracerebrally with MZM-13 developed clinically asymptomatic lesions in the central nervous system characterized by acute and chronic inflammation and degeneration of myelin in cranial and spinal nerve roots. Restriction endonuclease analysis of viral deoxyribonucleic acid isolated from these two viruses indicated that MZM-13 and MZM-14 are identical and are closely related to chimpanzee CMV. No similarity in restriction endonuclease fragment patterns was found between MZM virus and the Towne and Clegg strains of human CMV."}
{"id": "PMID:227787", "title": "Intracellular localization of the dermonecrotic toxin of Bordetella pertussis.", "content": "Localization of the heat-labile dermonecrotic toxin of Bordetella pertussis strain 114 grown in chemically defined Stainer-Scholte medium was studied by using skin reaction in 4-day-old suckling mice as the assay for toxin. Through log phase and into stationary phase of growth the toxin was cell associated and not detected in the culture supernatant. Only about 4% of the activity present in a suspension of lysed cells was detected in a suspension of whole cells, and the dermonecrotic activity was not released by subjecting whole cells to osmotic shock, a procedure that releases proteins from the periplasmic space of many gram-negative bacteria. After cell lysis and preparation of soluble and membrane fractions, 73 to 80% of the activity in the cell lysate was recovered in the soluble fraction, with only 3 to 6% present in a membrane fraction. Further evidence for the intracellular cytoplasmic localization of the dermonecrotic toxin was the insensitivity of the toxin to trypsin treatment of whole cells. Treatment of whole cells with trypsin (80 micrograms/ml) for 20 min at 37 degrees C did not decrease dermonecrotic or malate dehydrogenase activities, but did inhibit more than 95% of the extra-cytoplasmic adenylate cyclase activity. Identical trypsin treatment of a cell lysate decreased all the above activities by more than 90%.", "contents": "Intracellular localization of the dermonecrotic toxin of Bordetella pertussis. Localization of the heat-labile dermonecrotic toxin of Bordetella pertussis strain 114 grown in chemically defined Stainer-Scholte medium was studied by using skin reaction in 4-day-old suckling mice as the assay for toxin. Through log phase and into stationary phase of growth the toxin was cell associated and not detected in the culture supernatant. Only about 4% of the activity present in a suspension of lysed cells was detected in a suspension of whole cells, and the dermonecrotic activity was not released by subjecting whole cells to osmotic shock, a procedure that releases proteins from the periplasmic space of many gram-negative bacteria. After cell lysis and preparation of soluble and membrane fractions, 73 to 80% of the activity in the cell lysate was recovered in the soluble fraction, with only 3 to 6% present in a membrane fraction. Further evidence for the intracellular cytoplasmic localization of the dermonecrotic toxin was the insensitivity of the toxin to trypsin treatment of whole cells. Treatment of whole cells with trypsin (80 micrograms/ml) for 20 min at 37 degrees C did not decrease dermonecrotic or malate dehydrogenase activities, but did inhibit more than 95% of the extra-cytoplasmic adenylate cyclase activity. Identical trypsin treatment of a cell lysate decreased all the above activities by more than 90%."}
{"id": "PMID:227788", "title": "Endotoxin in vitro interactions with human neutrophils: depression of chemiluminescence, oxygen consumption, superoxide production, and killing.", "content": "Endotoxin was shown to depress neutrophil bactericidal activity while enhancing Nitro Blue Tetrazolium reduction and hexose monophosphate shunt activity. Separation of bactericidal action from oxidative metabolism suggests that the effect of endotoxin might involve the formation of reactive oxygen radicals such as superoxide. Chemiluminescence often accompanies metabolic activation of polymorphonuclear neutrophils (PMNs). However, human PMNs did not show chemiluminescence when challenged with endotoxin (lipopolysaccharide; LPS) or lipid A. Superoxide formation was also unaffected by endotoxin. In contrast, preincubation of PMNs with LPS for 30 min produced significant depression of chemiluminescence, oxygen consumption, and superoxide formation. Decreased chemiluminescence was not the result of complement consumption. In a cell-free system, superoxide was not scavenged by LPS, nor did LPS stimulate superoxide dismutase. Oxidase enzymes for reduced nicotinamide adenine dinucleotide or reduced nicotinamide adenine dinucleotide phosphate harvested from broken cells were not affected by LPS. The toxicity of LPS may reside in its ability to activate the PMNs while simultaneously blocking bactericidal capacity.", "contents": "Endotoxin in vitro interactions with human neutrophils: depression of chemiluminescence, oxygen consumption, superoxide production, and killing. Endotoxin was shown to depress neutrophil bactericidal activity while enhancing Nitro Blue Tetrazolium reduction and hexose monophosphate shunt activity. Separation of bactericidal action from oxidative metabolism suggests that the effect of endotoxin might involve the formation of reactive oxygen radicals such as superoxide. Chemiluminescence often accompanies metabolic activation of polymorphonuclear neutrophils (PMNs). However, human PMNs did not show chemiluminescence when challenged with endotoxin (lipopolysaccharide; LPS) or lipid A. Superoxide formation was also unaffected by endotoxin. In contrast, preincubation of PMNs with LPS for 30 min produced significant depression of chemiluminescence, oxygen consumption, and superoxide formation. Decreased chemiluminescence was not the result of complement consumption. In a cell-free system, superoxide was not scavenged by LPS, nor did LPS stimulate superoxide dismutase. Oxidase enzymes for reduced nicotinamide adenine dinucleotide or reduced nicotinamide adenine dinucleotide phosphate harvested from broken cells were not affected by LPS. The toxicity of LPS may reside in its ability to activate the PMNs while simultaneously blocking bactericidal capacity."}
{"id": "PMID:227789", "title": "In vitro replication of infectious bursal disease virus in established lymphoid cell lines and chicken B lymphocytes.", "content": "The in vitro susceptibility of chicken lymphocytes to a wild strains of infectious bursal disease virus was investigated by using immunofluorescence and virus assays as infection criteria. A variety of Marek's disease lymphoblastoid cell lines, all of thymus (T-cell) origin, were refractory to virus exposure. However, a bursa (B-cell)-derived lymphoblastoid cell line from an avian leukosis virus-induced tumor was highly susceptible. Viral antigen appeared in the cytoplasm of 20 to 30% of the cells, and large amounts of cell-free virus were released, with maximum yields occurring by 3 days postinfeciton. The virus also replicated in a small percentage of normal lymphocytes prepared from lymphoid tissues and peripheral blood of chickens. Pretreatment of the lymphocytes, with heat-inactivated anti-B-cell serum or with antiserum against fowl immunoglobulin M before inoculating them with the virus blocked the virus infection; no blocking occurred with anti-T-cell serum or with specific antiserum against fowl immunoglobulin G or immunoglobulin A. This suggests that surface immunoglobulin M-bearing B-lymphocytes were the target cells for infection.", "contents": "In vitro replication of infectious bursal disease virus in established lymphoid cell lines and chicken B lymphocytes. The in vitro susceptibility of chicken lymphocytes to a wild strains of infectious bursal disease virus was investigated by using immunofluorescence and virus assays as infection criteria. A variety of Marek's disease lymphoblastoid cell lines, all of thymus (T-cell) origin, were refractory to virus exposure. However, a bursa (B-cell)-derived lymphoblastoid cell line from an avian leukosis virus-induced tumor was highly susceptible. Viral antigen appeared in the cytoplasm of 20 to 30% of the cells, and large amounts of cell-free virus were released, with maximum yields occurring by 3 days postinfeciton. The virus also replicated in a small percentage of normal lymphocytes prepared from lymphoid tissues and peripheral blood of chickens. Pretreatment of the lymphocytes, with heat-inactivated anti-B-cell serum or with antiserum against fowl immunoglobulin M before inoculating them with the virus blocked the virus infection; no blocking occurred with anti-T-cell serum or with specific antiserum against fowl immunoglobulin G or immunoglobulin A. This suggests that surface immunoglobulin M-bearing B-lymphocytes were the target cells for infection."}
{"id": "PMID:227790", "title": "Reactivation of polyoma virus in kidneys of persistently infected mice during pregnancy.", "content": "Female mice infected at birth with 10(7) 50% tissue culture infective doses of polyoma virus were mated when at least 6 weeks old. Polyoma was not detected in any tissues of 27 female mice before mating except for trace amounts in the kidneys of 2 mice, but late in gestation polyoma virus could be found in the kidneys of 21 of 38 mice with titers of 10(3.7) to 10(6.2) 50% tissue culture infective doses per gram of kidney. The virus was not detected in the brain, salivary gland, lung, liver, spleen, ovaries, placenta, or fetuses during gestation. Nonpregnant females were injected with female sex hormones over a period of 17 days, and polyoma was then detected in kidneys of 4 of 18 mice. Treatment of cultures of mouse embryo fibroblasts with either sexhormones or a glucocorticosteroid resulted in approximately a threefold increase in the rate of infection of cells with polyoma virus.", "contents": "Reactivation of polyoma virus in kidneys of persistently infected mice during pregnancy. Female mice infected at birth with 10(7) 50% tissue culture infective doses of polyoma virus were mated when at least 6 weeks old. Polyoma was not detected in any tissues of 27 female mice before mating except for trace amounts in the kidneys of 2 mice, but late in gestation polyoma virus could be found in the kidneys of 21 of 38 mice with titers of 10(3.7) to 10(6.2) 50% tissue culture infective doses per gram of kidney. The virus was not detected in the brain, salivary gland, lung, liver, spleen, ovaries, placenta, or fetuses during gestation. Nonpregnant females were injected with female sex hormones over a period of 17 days, and polyoma was then detected in kidneys of 4 of 18 mice. Treatment of cultures of mouse embryo fibroblasts with either sexhormones or a glucocorticosteroid resulted in approximately a threefold increase in the rate of infection of cells with polyoma virus."}
{"id": "PMID:227791", "title": "Analysis of the adhesion step in the herpes simplex virus antibody-dependent cellular cytotoxicity system.", "content": "The lysis of herpes simplex virus-infected tissue culture cells by antibody-dependent cellular cytotoxicity (ADCC) requires a preliminary step in which effector cells adhere to the immunoglobulin G antibody-coated targets. To study the adhesion step, we made use of two observations: (i) some of the mononuclear cells in human blood form rosettes with antibody-coated target cells, and (ii) most ADCC effector cells can be removed by allowing mononuclear cells to adhere to monolayers of antibody-sensitized tissue culture cells. The effect of various experimental conditions on the adhesion step was assessed in ADCC cultures both at unit gravity and after centrifugation. At unit gravity both rosette formation and monolayer adhesion were partially reduced at 4 degrees C as compared to 37 degrees C. Both were also partially inhibited in glucose-free medium containing sodium azide and 2-deoxyglucose but were unaffected in glucose-free medium containing only one of these energy inhibitors. In contrast, after centrifugation neither reaction was inhibited at 4 degrees C or in glucose-free medium with sodium azide and 2-deoxyglucose. Cytochalasin B but not colchicine suppressed both reactions. Inhibition by cytochalasin B could not be reversed by centrifugation. Both reactions were independent of extracellular Ca(2+) and Mg(2+) and were unaffected by rendering mononuclear cells cytotoxically inactive by brief heat shock. These findings indicate that the adhesion step in ADCC directed against virus-infected or uninfected tissue culture cells is only modestly dependent on effector cell energy generation, that centrifugation greatly reduces this dependence, and that microfilaments but not microtubules are necessary. The modest ambient temperature and energy requirements, independence of extracellular divalent cations, lack of sensitivity to colchicine, and relative resistance to supraphysiological temperature serve to distinguish the adhesion step from the lytic step in ADCC.", "contents": "Analysis of the adhesion step in the herpes simplex virus antibody-dependent cellular cytotoxicity system. The lysis of herpes simplex virus-infected tissue culture cells by antibody-dependent cellular cytotoxicity (ADCC) requires a preliminary step in which effector cells adhere to the immunoglobulin G antibody-coated targets. To study the adhesion step, we made use of two observations: (i) some of the mononuclear cells in human blood form rosettes with antibody-coated target cells, and (ii) most ADCC effector cells can be removed by allowing mononuclear cells to adhere to monolayers of antibody-sensitized tissue culture cells. The effect of various experimental conditions on the adhesion step was assessed in ADCC cultures both at unit gravity and after centrifugation. At unit gravity both rosette formation and monolayer adhesion were partially reduced at 4 degrees C as compared to 37 degrees C. Both were also partially inhibited in glucose-free medium containing sodium azide and 2-deoxyglucose but were unaffected in glucose-free medium containing only one of these energy inhibitors. In contrast, after centrifugation neither reaction was inhibited at 4 degrees C or in glucose-free medium with sodium azide and 2-deoxyglucose. Cytochalasin B but not colchicine suppressed both reactions. Inhibition by cytochalasin B could not be reversed by centrifugation. Both reactions were independent of extracellular Ca(2+) and Mg(2+) and were unaffected by rendering mononuclear cells cytotoxically inactive by brief heat shock. These findings indicate that the adhesion step in ADCC directed against virus-infected or uninfected tissue culture cells is only modestly dependent on effector cell energy generation, that centrifugation greatly reduces this dependence, and that microfilaments but not microtubules are necessary. The modest ambient temperature and energy requirements, independence of extracellular divalent cations, lack of sensitivity to colchicine, and relative resistance to supraphysiological temperature serve to distinguish the adhesion step from the lytic step in ADCC."}
{"id": "PMID:227792", "title": "Hemagglutinin mutants of swine influenza virus differing in replication characteristics in their natural host.", "content": "In two mutant clones (L and H) of A/NJ/11/76 (Hsw 1N1) influenza viruses which differ slightly antigenically and markedly in replication characteristics in chicken embryos and Madin Darby canine kidney cells, these pleiotropic differences are mediated by mutation in the hemagglutinin gene (E. D. Kilbourne, Proc. Natl. Acad. Sci. U.S.A. 75:6258--6262, 1978). Experimental infection of swine with either the mutant L and H clones or recombinant viruses differing genetically only with respect to the presence of L or H hemagglutinin demonstrated greater infectivity for the natural host of viruses bearing the L hemagglutinin. Introduction of the L but not the H hemagglutinin gene into the human influenza virus A/PR/8/34 rendered it infective for swine. Both L and H variants were isolated from pigs naturally infected with contemporary swine influenza viruses when selective conditions for the suppression of the more prevalent L mutant were employed. The L and H mutants of swine influenza virus are yet another example of viral dimorphism in nature and probably are not mere artifacts of laboratory selection. In any event, the frequent apparent allelic appearance of the two forms suggests frequent mutation and/or reversion involving a point mutation in the hemagglutinin gene. The present studies demonstrate the importance of a single gene in the pathogenesis of an influenza viral infection in its natural host.", "contents": "Hemagglutinin mutants of swine influenza virus differing in replication characteristics in their natural host. In two mutant clones (L and H) of A/NJ/11/76 (Hsw 1N1) influenza viruses which differ slightly antigenically and markedly in replication characteristics in chicken embryos and Madin Darby canine kidney cells, these pleiotropic differences are mediated by mutation in the hemagglutinin gene (E. D. Kilbourne, Proc. Natl. Acad. Sci. U.S.A. 75:6258--6262, 1978). Experimental infection of swine with either the mutant L and H clones or recombinant viruses differing genetically only with respect to the presence of L or H hemagglutinin demonstrated greater infectivity for the natural host of viruses bearing the L hemagglutinin. Introduction of the L but not the H hemagglutinin gene into the human influenza virus A/PR/8/34 rendered it infective for swine. Both L and H variants were isolated from pigs naturally infected with contemporary swine influenza viruses when selective conditions for the suppression of the more prevalent L mutant were employed. The L and H mutants of swine influenza virus are yet another example of viral dimorphism in nature and probably are not mere artifacts of laboratory selection. In any event, the frequent apparent allelic appearance of the two forms suggests frequent mutation and/or reversion involving a point mutation in the hemagglutinin gene. The present studies demonstrate the importance of a single gene in the pathogenesis of an influenza viral infection in its natural host."}
{"id": "PMID:227793", "title": "Cell-mediated immunity to cytomegalovirus in immunocompromised patients: effect of radiation or chemotherapy.", "content": "Using the techniques of complement fixation, immunofluorescence, and in vitro lymphocyte transformation (LTF), we studied the humoral antibody and cell-mediated immunity to cytomegalovirus (CMV) in normal subjects, in patients with cancer receiving localized or nonlocalized radiation, and in renal transplant recipients on immunosuppressive chemotherapy. The LTF activity was determined by the whole blood microassay, using four strains of CMV (AD-169, Davis, Veca, and Towne), AD-169 early antigen, and phytohemagglutinin (PAH). The renal transplant subjects manifested significantly depressed LTF responses to PHA and CMV and frequent presence of immunoglobulin M and early antigen-specific antibody response. The depressed LTF response to CMV recovered significantly 2 years after transplantation. The cancer patients were also characterized by a profound drop in LTF responses to PHA and CMV and in immunoglobulin M and early antigen-specific antibody response after nonlocalized radiation. LTF responses to AD-169 and Towne strains were found to be higher than those to Davis and Veca strains. The LTF response to PHA declined with age. However, LTF responses to specific CMV antigens were found to be somewhat increased with advancing age. These observations suggest that transplantation-associated suppression of CMV-specific cell-mediated immunity may improve a few years after transplantation despite continued immunosuppressive therapy.", "contents": "Cell-mediated immunity to cytomegalovirus in immunocompromised patients: effect of radiation or chemotherapy. Using the techniques of complement fixation, immunofluorescence, and in vitro lymphocyte transformation (LTF), we studied the humoral antibody and cell-mediated immunity to cytomegalovirus (CMV) in normal subjects, in patients with cancer receiving localized or nonlocalized radiation, and in renal transplant recipients on immunosuppressive chemotherapy. The LTF activity was determined by the whole blood microassay, using four strains of CMV (AD-169, Davis, Veca, and Towne), AD-169 early antigen, and phytohemagglutinin (PAH). The renal transplant subjects manifested significantly depressed LTF responses to PHA and CMV and frequent presence of immunoglobulin M and early antigen-specific antibody response. The depressed LTF response to CMV recovered significantly 2 years after transplantation. The cancer patients were also characterized by a profound drop in LTF responses to PHA and CMV and in immunoglobulin M and early antigen-specific antibody response after nonlocalized radiation. LTF responses to AD-169 and Towne strains were found to be higher than those to Davis and Veca strains. The LTF response to PHA declined with age. However, LTF responses to specific CMV antigens were found to be somewhat increased with advancing age. These observations suggest that transplantation-associated suppression of CMV-specific cell-mediated immunity may improve a few years after transplantation despite continued immunosuppressive therapy."}
{"id": "PMID:227794", "title": "Surface markers and size of lymphocytes in human umbilical cord blood stimulated into deoxyribonucleic acid synthesis by Epstein-Barr Virus.", "content": "We characterized subpopulations of lymphocytes in human umbilical cord blood which are stimulated into deoxyribonucleic acid synthesis by Epstein-Barr virus. Lymphocytes were examined simultaneously for deoxyribonucleic acid synthesis by autoradiography and for surface markers by rosette formation with sheep erythrocytes or erythrocytes coated with antibody and mouse complement (EAC). The subpopulation which incorporated [3H]thymidine after exposure to virus consisted mainly of cells which formed rosettes with EAC. Lymphocytes were enriched or depleted of thymus-derived lymphocytes (T cells), null cells, or cells forming rosettes with EAC. The extent of sensitivity of the cells to stimulation by Epstein-Barr virus correlated with the proportion of the population which formed rosettes with EAC. When mononuclear cell populations were depleted of T lymphocytes and then fractionated by size, small lymphocytes showed higher rates of deoxyribonucleic acid synthesis after virus exposure and higher transformation frequency than did larger cells or unfractionated cells. Thus, the cells which are stimulated into deoxyribonucleic acid synthesis by Epstein-Barr virus appear to be the same as cells which are ultimately transformed.", "contents": "Surface markers and size of lymphocytes in human umbilical cord blood stimulated into deoxyribonucleic acid synthesis by Epstein-Barr Virus. We characterized subpopulations of lymphocytes in human umbilical cord blood which are stimulated into deoxyribonucleic acid synthesis by Epstein-Barr virus. Lymphocytes were examined simultaneously for deoxyribonucleic acid synthesis by autoradiography and for surface markers by rosette formation with sheep erythrocytes or erythrocytes coated with antibody and mouse complement (EAC). The subpopulation which incorporated [3H]thymidine after exposure to virus consisted mainly of cells which formed rosettes with EAC. Lymphocytes were enriched or depleted of thymus-derived lymphocytes (T cells), null cells, or cells forming rosettes with EAC. The extent of sensitivity of the cells to stimulation by Epstein-Barr virus correlated with the proportion of the population which formed rosettes with EAC. When mononuclear cell populations were depleted of T lymphocytes and then fractionated by size, small lymphocytes showed higher rates of deoxyribonucleic acid synthesis after virus exposure and higher transformation frequency than did larger cells or unfractionated cells. Thus, the cells which are stimulated into deoxyribonucleic acid synthesis by Epstein-Barr virus appear to be the same as cells which are ultimately transformed."}
{"id": "PMID:227795", "title": "Effect of cholera toxin on the antiviral and anticellular activities of human leukocyte interferon.", "content": "Cholera toxin added into cell cultures together with human leukocyte interferon inhibited the establishment of the antiviral state by interferon but not the anticellular activity of interferon in human cells. Sensitivities of various human cell lines to anticellular activities of interferon and cholera toxin were compared, but no direct correlation between both activities were demonstrated. These results suggest that antiviral and anticellular activities of interferon are due to different mechanism of actions, and cholera toxin does not act directly on the receptor site for interferon.", "contents": "Effect of cholera toxin on the antiviral and anticellular activities of human leukocyte interferon. Cholera toxin added into cell cultures together with human leukocyte interferon inhibited the establishment of the antiviral state by interferon but not the anticellular activity of interferon in human cells. Sensitivities of various human cell lines to anticellular activities of interferon and cholera toxin were compared, but no direct correlation between both activities were demonstrated. These results suggest that antiviral and anticellular activities of interferon are due to different mechanism of actions, and cholera toxin does not act directly on the receptor site for interferon."}
{"id": "PMID:227796", "title": "Potentiation of interferon activity by mixed preparations of fibroblast and immune interferon.", "content": "Mixed preparations of fibroblast and immune interferons interacted with cells synergistically to cause the development of a much greater level of protection than expected on the basis of their separate activities. This increased level of protection was 5- to 20-fold greater than expected on the basis of a simple additive effect of the interferons. The potentiating factor copurified with both fibroblast interferon and immune interferon as they were partially purified. The potentiation was not an artifact of a more rapid development of immune interferon-induced antiviral resistance in the presence of fibroblast interferon. The results were consistent with the hypothesis that fibroblast and immune interferons mutually potentiate each other, thus supporting the supposition that they have different modes of action.", "contents": "Potentiation of interferon activity by mixed preparations of fibroblast and immune interferon. Mixed preparations of fibroblast and immune interferons interacted with cells synergistically to cause the development of a much greater level of protection than expected on the basis of their separate activities. This increased level of protection was 5- to 20-fold greater than expected on the basis of a simple additive effect of the interferons. The potentiating factor copurified with both fibroblast interferon and immune interferon as they were partially purified. The potentiation was not an artifact of a more rapid development of immune interferon-induced antiviral resistance in the presence of fibroblast interferon. The results were consistent with the hypothesis that fibroblast and immune interferons mutually potentiate each other, thus supporting the supposition that they have different modes of action."}
{"id": "PMID:227797", "title": "Inability of passively acquired antibody to protect lambs against experimental pasteurellosis.", "content": "An experimental model of pneumonic pasteurellosis in sheep was used to investigate the role of serum antibody in resistance to this disease. Lambs which had been vaccinated with a sodium salicylate extract of Pasteurella haemolytica type A1 were protected against challenge with PI3 virus followed by P. haemolytica type A1 7 days later. The majority of untreated lambs and lambs which had received either 200 ml of antiserum to P. haemolytica or 200 ml of control serum intraperitoneally 18 h before infection with P. haemolytica type A1 succumbed to the challenge. Lymphocytes from vaccinated lambs showed a specific proliferative response when exposed to P. haemolytica type A1 sodium salicylate extract, and this response increased after exposure of these animals to P. haemolytica type A1 in aerosol. The results indicate that the humoral immune response alone is incapable of affording protection against experimental pasteurellosis and that cell-mediated immunity may play an important part in resistance to this disease.", "contents": "Inability of passively acquired antibody to protect lambs against experimental pasteurellosis. An experimental model of pneumonic pasteurellosis in sheep was used to investigate the role of serum antibody in resistance to this disease. Lambs which had been vaccinated with a sodium salicylate extract of Pasteurella haemolytica type A1 were protected against challenge with PI3 virus followed by P. haemolytica type A1 7 days later. The majority of untreated lambs and lambs which had received either 200 ml of antiserum to P. haemolytica or 200 ml of control serum intraperitoneally 18 h before infection with P. haemolytica type A1 succumbed to the challenge. Lymphocytes from vaccinated lambs showed a specific proliferative response when exposed to P. haemolytica type A1 sodium salicylate extract, and this response increased after exposure of these animals to P. haemolytica type A1 in aerosol. The results indicate that the humoral immune response alone is incapable of affording protection against experimental pasteurellosis and that cell-mediated immunity may play an important part in resistance to this disease."}
{"id": "PMID:227798", "title": "Prevalence of antibody to the Norwalk virus in various countries.", "content": "Serum samples from children and adults from several countries were tested by radioimmunoassay for antibody to the Norwalk virus. Antibody was commonly found in adults from all the countries tested. Antibody appears to be acquired more rapidly in children from underdeveloped countries than in children from the United States.", "contents": "Prevalence of antibody to the Norwalk virus in various countries. Serum samples from children and adults from several countries were tested by radioimmunoassay for antibody to the Norwalk virus. Antibody was commonly found in adults from all the countries tested. Antibody appears to be acquired more rapidly in children from underdeveloped countries than in children from the United States."}
{"id": "PMID:227799", "title": "Natural killing of herpes simplex virus type 1-infected target cells: normal human responses and influence of antiviral antibody.", "content": "Studies of a mouse model of genetic resistance to herpes simplex virus type 1 (HSV-1) indicate that the marrow-dependent effector cell of allogeneic resistance plays an important role in natural resistance to this virus infection. Since the marrow-dependent effector cell appears to be closely related to the natural killer (NK) cells, an NK assay with HSV-1-infected fibroblasts [NK(HSV-1)] has been developed to study this resistance mechanism in humans. Incubation of effector and target cells for 12 to 14 h gave the greatest percent specific release (%SR) and kept spontaneous (51)Cr release from infected target cells below 35%. Patients with Bruton's agammaglobulinemia demonstrated significant kill indicating antiviral antibody was not necessary. Seropositive individuals gave a 9% greater%SR than seronegative individuals. Depletion of B-cells consistently diminished NK (HSV-1) for seropositive individuals and augmented kill for seronegative individuals. Although antiviral antibody produced in culture may contribute to NK (HSV-1), depletion of B-cells allowed quantitation of NK (HSV-1) to the exclusion of most of the antibody-dependent kill. The NK cells detected by this assay showed many of the properties reported for NK cells with K562 targets. Two patients with severe herpesvirus infections demonstrated NK (HSV-1) responses greater than 2 standard deviations below the normal mean. Since normal individuals with virus infections have higher rather than lower natural kill, the low NK (HSV-1) may reflect their susceptibility to the virus infection.", "contents": "Natural killing of herpes simplex virus type 1-infected target cells: normal human responses and influence of antiviral antibody. Studies of a mouse model of genetic resistance to herpes simplex virus type 1 (HSV-1) indicate that the marrow-dependent effector cell of allogeneic resistance plays an important role in natural resistance to this virus infection. Since the marrow-dependent effector cell appears to be closely related to the natural killer (NK) cells, an NK assay with HSV-1-infected fibroblasts [NK(HSV-1)] has been developed to study this resistance mechanism in humans. Incubation of effector and target cells for 12 to 14 h gave the greatest percent specific release (%SR) and kept spontaneous (51)Cr release from infected target cells below 35%. Patients with Bruton's agammaglobulinemia demonstrated significant kill indicating antiviral antibody was not necessary. Seropositive individuals gave a 9% greater%SR than seronegative individuals. Depletion of B-cells consistently diminished NK (HSV-1) for seropositive individuals and augmented kill for seronegative individuals. Although antiviral antibody produced in culture may contribute to NK (HSV-1), depletion of B-cells allowed quantitation of NK (HSV-1) to the exclusion of most of the antibody-dependent kill. The NK cells detected by this assay showed many of the properties reported for NK cells with K562 targets. Two patients with severe herpesvirus infections demonstrated NK (HSV-1) responses greater than 2 standard deviations below the normal mean. Since normal individuals with virus infections have higher rather than lower natural kill, the low NK (HSV-1) may reflect their susceptibility to the virus infection."}
{"id": "PMID:227800", "title": "Depression of vaccinal immunity to Marek's disease by infection with reticuloendotheliosis virus.", "content": "The effect of infection with low-virulence, tissue culture-propagated strains of reticuloendotheliosis virus (REV) on protective vaccinal immunity against Marek's disease (MD) lymphomas was investigated. Vaccinated chickens inoculated at hatching with greater than 10(4) focus-forming units of REV and challenged with MD virus were poorly protected against MD lesion development as indicated by protective indices of 53 to 79% for strain CS (P less than 0.05) and 42 to 49% for strain T (P less than 0.01) compared to 78 to 100% for REV-free controls. Furthermore, the response of blood lymphocytes to mitogen stimulation and the antibody response to sheep erythrocytes and Brucella abortus were less in REV-inoculated chickens than in controls. The REV-induced depression of immune responses was more severe in chickens infected with mildly pathogenic strain T than in chickens infected with the apathogenic strain CS and was generally transient with both virus strains. Little or no depression of immune responses was observed in chickens inoculated with less than 10(3) focus-forming units of REV. These studies extend knowledge on the immunodepressive ability of low-virulence REV strains and establish that infection with these viruses depresses certain parameters of MD vaccinal immunity, an important model for cellular immunity against virus-induced neoplasia in the chicken.", "contents": "Depression of vaccinal immunity to Marek's disease by infection with reticuloendotheliosis virus. The effect of infection with low-virulence, tissue culture-propagated strains of reticuloendotheliosis virus (REV) on protective vaccinal immunity against Marek's disease (MD) lymphomas was investigated. Vaccinated chickens inoculated at hatching with greater than 10(4) focus-forming units of REV and challenged with MD virus were poorly protected against MD lesion development as indicated by protective indices of 53 to 79% for strain CS (P less than 0.05) and 42 to 49% for strain T (P less than 0.01) compared to 78 to 100% for REV-free controls. Furthermore, the response of blood lymphocytes to mitogen stimulation and the antibody response to sheep erythrocytes and Brucella abortus were less in REV-inoculated chickens than in controls. The REV-induced depression of immune responses was more severe in chickens infected with mildly pathogenic strain T than in chickens infected with the apathogenic strain CS and was generally transient with both virus strains. Little or no depression of immune responses was observed in chickens inoculated with less than 10(3) focus-forming units of REV. These studies extend knowledge on the immunodepressive ability of low-virulence REV strains and establish that infection with these viruses depresses certain parameters of MD vaccinal immunity, an important model for cellular immunity against virus-induced neoplasia in the chicken."}
{"id": "PMID:227801", "title": "Vitiligo treated with ACTH.", "content": "Six of 20 patients with extensive vitiligo treated with ACTH experienced repigmentation at the end of 15 weeks. However, depigmentation recurred when the treatment was stopped.", "contents": "Vitiligo treated with ACTH. Six of 20 patients with extensive vitiligo treated with ACTH experienced repigmentation at the end of 15 weeks. However, depigmentation recurred when the treatment was stopped."}
{"id": "PMID:227802", "title": "Herpes virus production as a marker of repair in ultra-violet irradiated human skin cells of different origin.", "content": "Confluent cultures of human skin fibroblasts were irradiated with ultra-violet light 0 to 48 hours before infection with herpes simplex virus type 1 (HSV). The one-cycle viral yield was measured. Different responses were obtained according to the origin of the host cells. (1) Cells from three normal donors showed a dose-dependent recovery of HSV production during the 36--40 hours following U.V. exposure. The recovery was maximal for a dose at which a plateau level of unscheduled DNA synthesis (UDS) was reached (24 Jm-2). (2) In a xeroderma pigmentosum (XP) heterozygote line from a mother of XP children, the level of UDS after irradiation up to 48Jm-2 was normal whereas the extent of recovery of HSV production capacity was lower than that of the normal lines. (3) In strains from two cases of XP children, with a normal UDS (XP variants), the recovery process was slowed down and its extent was lower than in normal or XP heterozygote cells. (4) Excision-deficient XP strains from eight cases of XP children presented either no recovery (two strains having the lowest UDS, less than 2 per cent) or a small recovery, the extent of which was in good agreement with the corresponding level of UDS (between 5 and 30 per cent). Measurement of this recovery seems to be a very sensitive assay for detecting differences in the repair abilities of U.V.-irradiated human skin cells of various origins.", "contents": "Herpes virus production as a marker of repair in ultra-violet irradiated human skin cells of different origin. Confluent cultures of human skin fibroblasts were irradiated with ultra-violet light 0 to 48 hours before infection with herpes simplex virus type 1 (HSV). The one-cycle viral yield was measured. Different responses were obtained according to the origin of the host cells. (1) Cells from three normal donors showed a dose-dependent recovery of HSV production during the 36--40 hours following U.V. exposure. The recovery was maximal for a dose at which a plateau level of unscheduled DNA synthesis (UDS) was reached (24 Jm-2). (2) In a xeroderma pigmentosum (XP) heterozygote line from a mother of XP children, the level of UDS after irradiation up to 48Jm-2 was normal whereas the extent of recovery of HSV production capacity was lower than that of the normal lines. (3) In strains from two cases of XP children, with a normal UDS (XP variants), the recovery process was slowed down and its extent was lower than in normal or XP heterozygote cells. (4) Excision-deficient XP strains from eight cases of XP children presented either no recovery (two strains having the lowest UDS, less than 2 per cent) or a small recovery, the extent of which was in good agreement with the corresponding level of UDS (between 5 and 30 per cent). Measurement of this recovery seems to be a very sensitive assay for detecting differences in the repair abilities of U.V.-irradiated human skin cells of various origins."}
{"id": "PMID:227803", "title": "Radical formation in pyrimidines. IV. 1,3-dimethyluracil, a non-hydrogen-bonding crystal.", "content": "Radical formation in single crystals of 1,3-dimethyluracil by X-irradiation has been studied by electron spin resonance at 9.5 GHz. This crystal contains no hydrogen bonds. Only Van der Waals forces are present. Accordingly, after X-irradiation at 300 K, the only radicals observed are those resulting from the excitation path: the H-addition radical at C5 and an H-abstraction radical from a methyl group. Irradiation with light of lambda more than 400 nm induces the transformation of the C5-addition into the C6-addition radical. INDO calculations indicate that the C6-addition radical is protonated at O4. Since this crystal does not contain N-H or O-H bonds, this protonation can only occur through proton-abstraction from a C-H bond of a neighbouring molecule by the carbonyl group. The presence of short contacts between C6 and O4 is taken to suggest that the abstraction occurs at C6.", "contents": "Radical formation in pyrimidines. IV. 1,3-dimethyluracil, a non-hydrogen-bonding crystal. Radical formation in single crystals of 1,3-dimethyluracil by X-irradiation has been studied by electron spin resonance at 9.5 GHz. This crystal contains no hydrogen bonds. Only Van der Waals forces are present. Accordingly, after X-irradiation at 300 K, the only radicals observed are those resulting from the excitation path: the H-addition radical at C5 and an H-abstraction radical from a methyl group. Irradiation with light of lambda more than 400 nm induces the transformation of the C5-addition into the C6-addition radical. INDO calculations indicate that the C6-addition radical is protonated at O4. Since this crystal does not contain N-H or O-H bonds, this protonation can only occur through proton-abstraction from a C-H bond of a neighbouring molecule by the carbonyl group. The presence of short contacts between C6 and O4 is taken to suggest that the abstraction occurs at C6."}
{"id": "PMID:227804", "title": "Study of factors affecting the antigen structure of the donor kidney. I. Interpretation of the relationship between periodate pretreatment and the rejection phenomena of canine kidney allografts.", "content": "Donor kidneys were preserved in a Collins-4 solution containing periodate in concentrations of 10(-2) and 10(-4) mole/l, respectively, in an attempt to oxidize the carbohydrate components of the antigen-carrying membrane surfaces and thus to influence the rejection phenomena exhibited by the allogeneic kidney. All kidneys were, however, rejected as a result of a hyperacute reaction indicating that periodate did not react with the hydrophobic membrane structures in vivo. Not only did the antigen thus remain unchanged but the vulnerability of other renal structures to the destructive effect of the killer cells also increased as a result of toxic damage.", "contents": "Study of factors affecting the antigen structure of the donor kidney. I. Interpretation of the relationship between periodate pretreatment and the rejection phenomena of canine kidney allografts. Donor kidneys were preserved in a Collins-4 solution containing periodate in concentrations of 10(-2) and 10(-4) mole/l, respectively, in an attempt to oxidize the carbohydrate components of the antigen-carrying membrane surfaces and thus to influence the rejection phenomena exhibited by the allogeneic kidney. All kidneys were, however, rejected as a result of a hyperacute reaction indicating that periodate did not react with the hydrophobic membrane structures in vivo. Not only did the antigen thus remain unchanged but the vulnerability of other renal structures to the destructive effect of the killer cells also increased as a result of toxic damage."}
{"id": "PMID:227808", "title": "Intracisternal A particles in preimplantation embryos of feral mice (Mus musculus).", "content": "In embryos of feral mice, intracisternal A particles (IAP) are not observed in zygotes, but large numbers are seen budding into the endoplasmic reticulum at the 2-cell stage. In subsequent cleavage stages very few IAP are present. Organelles and developmental changes in organelles during the preimplantation period are characteristic of those described previously in embryos of laboratory mice.", "contents": "Intracisternal A particles in preimplantation embryos of feral mice (Mus musculus). In embryos of feral mice, intracisternal A particles (IAP) are not observed in zygotes, but large numbers are seen budding into the endoplasmic reticulum at the 2-cell stage. In subsequent cleavage stages very few IAP are present. Organelles and developmental changes in organelles during the preimplantation period are characteristic of those described previously in embryos of laboratory mice."}
{"id": "PMID:227809", "title": "Influence of inactivated Sendai virus on early events in polyomavirus infection of permissive and nonpermissive host cells.", "content": "Quantitative radiochemical investigations have been performed regarding the influence of betapropiolactone-inactivated Sendai virus on the early events of interaction of polyomavirus with permissive and nonpermissive cells. These experiments have shown: (i) Sendai virus did not increase polyomavirus adsorption on permissive or nonpermissive cells; (ii) Sendai virus induced polyomavirus elution from permissive and nonpermissive cells during the first 40 min and 6 h postinfection, respectively; and (iii) Sendai virus promoted the penetration of polyomavirus into lysosomes only in nonpermissive cells. The maximal amounts of radioactively labeled virion DNA and viral coat proteins were found in lysosomes at 2--3 h postinfection.", "contents": "Influence of inactivated Sendai virus on early events in polyomavirus infection of permissive and nonpermissive host cells. Quantitative radiochemical investigations have been performed regarding the influence of betapropiolactone-inactivated Sendai virus on the early events of interaction of polyomavirus with permissive and nonpermissive cells. These experiments have shown: (i) Sendai virus did not increase polyomavirus adsorption on permissive or nonpermissive cells; (ii) Sendai virus induced polyomavirus elution from permissive and nonpermissive cells during the first 40 min and 6 h postinfection, respectively; and (iii) Sendai virus promoted the penetration of polyomavirus into lysosomes only in nonpermissive cells. The maximal amounts of radioactively labeled virion DNA and viral coat proteins were found in lysosomes at 2--3 h postinfection."}
{"id": "PMID:227810", "title": "Early alterations in the morphology of cytomegalovirus-infected human fibroblasts.", "content": "Cytomegalovirus-infected human fibroblasts developed large numbers of fine microvilli within 90 min after addition of virus. The structure of these microvilli gradually changed as the infection proceeded, although the infected cells were easily detected by their large number of processes. These processes may be involved in the increased transport of ions and nutrients into the infected cell.", "contents": "Early alterations in the morphology of cytomegalovirus-infected human fibroblasts. Cytomegalovirus-infected human fibroblasts developed large numbers of fine microvilli within 90 min after addition of virus. The structure of these microvilli gradually changed as the infection proceeded, although the infected cells were easily detected by their large number of processes. These processes may be involved in the increased transport of ions and nutrients into the infected cell."}
{"id": "PMID:227811", "title": "Argentine hemorrhagic fever: a primate model.", "content": "Experimental Junin virus infection of a New World primate, Callithrix jacchus, was evaluated. The virus produced anorexia, loss of weight, thrombocytopenia, leukopenia, and hemorrhagic and neurological symptoms and terminated in death. Virus was recovered from urine, blood samples and all tissues taken at autopsy. These preliminary observations show that several aspects of the experimental disease in C. jacchus are quite similar to severe natural Argentine hemorrhagic fever of man.", "contents": "Argentine hemorrhagic fever: a primate model. Experimental Junin virus infection of a New World primate, Callithrix jacchus, was evaluated. The virus produced anorexia, loss of weight, thrombocytopenia, leukopenia, and hemorrhagic and neurological symptoms and terminated in death. Virus was recovered from urine, blood samples and all tissues taken at autopsy. These preliminary observations show that several aspects of the experimental disease in C. jacchus are quite similar to severe natural Argentine hemorrhagic fever of man."}
{"id": "PMID:227807", "title": "Identification and evaluation of the contribution of the chemoreflex in the hemodynamic response to intracarotid administration of contrast materials in the conscious dog: comparison with the response to nicotine.", "content": "Intracarotid administration of ionic contrast material and nicotine in conscious, unsedated dogs caused similar biphasic reflex responses consisting of initial decreases followed by increases in heart rate and pressures. Both phases were characterized by increases in respiratory amplitude. The initial hypotension was not observed when heart rate was maintained constant. The initial bradycardia was absent after denervation of the carotid body and cholinergic blockade. The tachycardia was attenuated after ligation of the internal carotid artery and beta adrenergic blockade. Hwever, the hypertension persisted after denervation of the carotid body and ligation of the internal carotid artery but was attenuated after alpha adrenergic blockade. Nonionic contrast material caused almost no reflex hemodynamic effects. Like noxious substances such as nicotine, ionic contrast materials cause complex hemodynamic effects as a consequence of actions on the cardiovascular centers of the brain, carotid body chemoreceptors, and chemosensitive tissue in the external carotid circulation.", "contents": "Identification and evaluation of the contribution of the chemoreflex in the hemodynamic response to intracarotid administration of contrast materials in the conscious dog: comparison with the response to nicotine. Intracarotid administration of ionic contrast material and nicotine in conscious, unsedated dogs caused similar biphasic reflex responses consisting of initial decreases followed by increases in heart rate and pressures. Both phases were characterized by increases in respiratory amplitude. The initial hypotension was not observed when heart rate was maintained constant. The initial bradycardia was absent after denervation of the carotid body and cholinergic blockade. The tachycardia was attenuated after ligation of the internal carotid artery and beta adrenergic blockade. Hwever, the hypertension persisted after denervation of the carotid body and ligation of the internal carotid artery but was attenuated after alpha adrenergic blockade. Nonionic contrast material caused almost no reflex hemodynamic effects. Like noxious substances such as nicotine, ionic contrast materials cause complex hemodynamic effects as a consequence of actions on the cardiovascular centers of the brain, carotid body chemoreceptors, and chemosensitive tissue in the external carotid circulation."}
{"id": "PMID:227812", "title": "Relationship between Epstein-Barr virus genome number, amount of nuclear antigen, and early antigen inducibility in diploid and tetraploid lymphoma cells of related origin.", "content": "In a collection of near-diploid and near-tetraploid Raji sublines and somatic Raji/Raji hybrids a linear relationship was found between the number of Epstein-Barr virus (EBV) genome copies and the relative amount of EBV-determined nuclear antigen per cell. Inducibility of the viral cycle by iododeoxyuridine and by P3HR-1 virus superinfection coulb be related to the number of resident EBV genome copies per haploid target cell. The implications of these findings are discussed.", "contents": "Relationship between Epstein-Barr virus genome number, amount of nuclear antigen, and early antigen inducibility in diploid and tetraploid lymphoma cells of related origin. In a collection of near-diploid and near-tetraploid Raji sublines and somatic Raji/Raji hybrids a linear relationship was found between the number of Epstein-Barr virus (EBV) genome copies and the relative amount of EBV-determined nuclear antigen per cell. Inducibility of the viral cycle by iododeoxyuridine and by P3HR-1 virus superinfection coulb be related to the number of resident EBV genome copies per haploid target cell. The implications of these findings are discussed."}
{"id": "PMID:227813", "title": "Immunofluorescent anti-Junin virus antibodies in Argentine hemorrhagic fever.", "content": "Immunofluorescent anti-Junin virus antibodies were detected in 15 nonfatal cases of Argentine hemorrhagic fever between the 2nd and 3rd week after onset of symptoms. In most cases, antibodies appeared by the day of clinical improvement, or between 2 and 4 days later. It was interesting to note that in 5 of 11 cases studied, the first positive serum sample presented anti-Junin virus immunofluorescent antibodies in IgA. In 2 of these 5 cases, IgA was the only immunoglobulin with antibody activity in the early positive serum sample.", "contents": "Immunofluorescent anti-Junin virus antibodies in Argentine hemorrhagic fever. Immunofluorescent anti-Junin virus antibodies were detected in 15 nonfatal cases of Argentine hemorrhagic fever between the 2nd and 3rd week after onset of symptoms. In most cases, antibodies appeared by the day of clinical improvement, or between 2 and 4 days later. It was interesting to note that in 5 of 11 cases studied, the first positive serum sample presented anti-Junin virus immunofluorescent antibodies in IgA. In 2 of these 5 cases, IgA was the only immunoglobulin with antibody activity in the early positive serum sample."}
{"id": "PMID:227814", "title": "A vesicular stomatitis virus (cytomegalovirus) pseudotype and its use in neutralization tests.", "content": "Infection with vesicular stomatitis virus (VSV) of human diploid cells preinfected with the AD-169 strain of human cytomegalovirus (CMV) resulted in the formation of a VSV (CMV) pseudotype. Its formation was favored by increasing the bicarbonate content in doubly-infected cultures. The pseudotype was capable of infecting not only human but also rabbit cells. Pseudotype particles formed after infection with the tl 17 mutant of VSV, which carries a thermolabile lesion in its neutralization antigen, were more stable at 45 degrees than the original tl 17 virus. The pseudotype was used in the neutralization test with human sera. All sera positive for CMV antibody in the complement-fixation (CF) test were also reactive in the neutralization test. In addition, numerous sera negative for CMV antibody in the CF test neutralized the pseudotype.", "contents": "A vesicular stomatitis virus (cytomegalovirus) pseudotype and its use in neutralization tests. Infection with vesicular stomatitis virus (VSV) of human diploid cells preinfected with the AD-169 strain of human cytomegalovirus (CMV) resulted in the formation of a VSV (CMV) pseudotype. Its formation was favored by increasing the bicarbonate content in doubly-infected cultures. The pseudotype was capable of infecting not only human but also rabbit cells. Pseudotype particles formed after infection with the tl 17 mutant of VSV, which carries a thermolabile lesion in its neutralization antigen, were more stable at 45 degrees than the original tl 17 virus. The pseudotype was used in the neutralization test with human sera. All sera positive for CMV antibody in the complement-fixation (CF) test were also reactive in the neutralization test. In addition, numerous sera negative for CMV antibody in the CF test neutralized the pseudotype."}
{"id": "PMID:227815", "title": "Altered nuclear structure during productive and abortive infections with SV40 DNA.", "content": "A striking alteration in nuclear morphology, detected by simian virus 40 (SV40) large-T antigen-specific immunofluorescence, occurred in cells infected by form I SV40 DNA but not by SV40 virions. This alteration did not require viral or cellular DNA synthesis.", "contents": "Altered nuclear structure during productive and abortive infections with SV40 DNA. A striking alteration in nuclear morphology, detected by simian virus 40 (SV40) large-T antigen-specific immunofluorescence, occurred in cells infected by form I SV40 DNA but not by SV40 virions. This alteration did not require viral or cellular DNA synthesis."}
{"id": "PMID:227819", "title": "[Physiological characteristics during exertion of Swiss Alpine and urban pubertal children].", "content": "On account of standardized examinations of circulatory and respiratory responses during the ride on the bicycle ergometer the physiological characteristic of Swiss children population from 12 to 15 years of age living in alpin and urban habitats is reported. The average maximum oxygen intake per kg body weight was 49-50 ml/min for alpin boys, 45-47 for urban boys, 39-41 for alpin girls and 37-39 for urban girls. Except for somatometric values, there is no other significant difference between alpin and urban children from the physiological point of view. A comparison of presented results with data from abroad does not show any disadvantageous properties of cardiorespiratory functions for Swiss boys and girls.", "contents": "[Physiological characteristics during exertion of Swiss Alpine and urban pubertal children]. On account of standardized examinations of circulatory and respiratory responses during the ride on the bicycle ergometer the physiological characteristic of Swiss children population from 12 to 15 years of age living in alpin and urban habitats is reported. The average maximum oxygen intake per kg body weight was 49-50 ml/min for alpin boys, 45-47 for urban boys, 39-41 for alpin girls and 37-39 for urban girls. Except for somatometric values, there is no other significant difference between alpin and urban children from the physiological point of view. A comparison of presented results with data from abroad does not show any disadvantageous properties of cardiorespiratory functions for Swiss boys and girls."}
{"id": "PMID:227820", "title": "Developmental pattern of glucose-6-phosphatase activity in the small intestine of the mouse fetus.", "content": "The distribution of glucose-6-phosphatase (G6Pase) activity in the epithelium of the small intestine in mouse embryos (the last 4 days of gestation) was studied by electron microscope cytochemistry and by enzymatic assays. At 16 days, the lead phosphate deposited by the cytochemical reaction is localized on the rough endoplasmic reticulum (RER) and nuclear envelope of very few cells in the duodenum and jejunum. Positive cells are more frequently seen in the upper part of the developing villi. At 17 days of gestation, a tremendous burst in RER differentiation is noticed in all parts of the small intestine and concomitantly glycogen disappears. At 18 days of gestation all the principal cells of the intestinal mucosa show a well differentiated positive RER and the enzyme is also present in the smooth endoplasmic reticulum. Biochemically, G6Pase activity is detected in the proximal 2 thirds of the small intestine at 17 days of gestation and appears at 18 days in the last third. Afterwards the activity increases up until birth. These results suggest (1) that the endoplasmic reticulum differentiates very late in the intestinal mucosa of mouse embryos (2) that the differentiation with respect to G6Pase is asynchronous between the enterocytes, (3) that for a given cell all the cisternae of RER are involved in G6Pase synthesis at the same moment and (4) that the enterocytes of the duodenum differentiate sooner and faster that those of the jejunum and ileum.", "contents": "Developmental pattern of glucose-6-phosphatase activity in the small intestine of the mouse fetus. The distribution of glucose-6-phosphatase (G6Pase) activity in the epithelium of the small intestine in mouse embryos (the last 4 days of gestation) was studied by electron microscope cytochemistry and by enzymatic assays. At 16 days, the lead phosphate deposited by the cytochemical reaction is localized on the rough endoplasmic reticulum (RER) and nuclear envelope of very few cells in the duodenum and jejunum. Positive cells are more frequently seen in the upper part of the developing villi. At 17 days of gestation, a tremendous burst in RER differentiation is noticed in all parts of the small intestine and concomitantly glycogen disappears. At 18 days of gestation all the principal cells of the intestinal mucosa show a well differentiated positive RER and the enzyme is also present in the smooth endoplasmic reticulum. Biochemically, G6Pase activity is detected in the proximal 2 thirds of the small intestine at 17 days of gestation and appears at 18 days in the last third. Afterwards the activity increases up until birth. These results suggest (1) that the endoplasmic reticulum differentiates very late in the intestinal mucosa of mouse embryos (2) that the differentiation with respect to G6Pase is asynchronous between the enterocytes, (3) that for a given cell all the cisternae of RER are involved in G6Pase synthesis at the same moment and (4) that the enterocytes of the duodenum differentiate sooner and faster that those of the jejunum and ileum."}
{"id": "PMID:227817", "title": "The pathology of head and neck tumors: salivary glands, part 3.", "content": "The term adenoma is applied to a rather wide variety of histopathologic entities in the salivary glands. These include tumors derived from the ductal epithelium and/or from myoepithelial cells and other salivary-gland elements, such as the sebaceous glands. Within the categories of mixed tumor (pleomorphic adenoma), monomorphic adenoma, clear-cell tumor, and sebaceous lesions, there are also several subtypes, each of which lends further credence to the germinative potential of the salivary tissues. Presented in this report is a clinicopathologic and histogenetic analysis of these lesions. Specifically discussed are mixed tumor, monomorphic adenoma, carcinoma ex-pleomorphic adenoma, clear-cell tumor, sebaceous lymphadenoma, and sebaceous carcinoma.", "contents": "The pathology of head and neck tumors: salivary glands, part 3. The term adenoma is applied to a rather wide variety of histopathologic entities in the salivary glands. These include tumors derived from the ductal epithelium and/or from myoepithelial cells and other salivary-gland elements, such as the sebaceous glands. Within the categories of mixed tumor (pleomorphic adenoma), monomorphic adenoma, clear-cell tumor, and sebaceous lesions, there are also several subtypes, each of which lends further credence to the germinative potential of the salivary tissues. Presented in this report is a clinicopathologic and histogenetic analysis of these lesions. Specifically discussed are mixed tumor, monomorphic adenoma, carcinoma ex-pleomorphic adenoma, clear-cell tumor, sebaceous lymphadenoma, and sebaceous carcinoma."}
{"id": "PMID:227818", "title": "The pathology of head and neck tumors: salivary glands, part 4.", "content": "Adenoid cystic carcinomas and adenocarcinomas of salivary tissues are more plentiful in minor than in major salivary glands. In the latter, they comprise no more than 10% of tumors. In both sites, however, their clinical course is characterized by local aggressiveness, recurrences, and a relatively torpid and protracted course, eventually leading to death. The clinicopathologic aspects of these two lesions form the major part of this report. Their behavior is contrasted with that of the two other lesions presented: heterotopic salivary tissue, which is seldom the site of neoplasia; and necrotizing sialometaplasia, a self-limited disorder that simulates malignancy both clinically and histopathologically.", "contents": "The pathology of head and neck tumors: salivary glands, part 4. Adenoid cystic carcinomas and adenocarcinomas of salivary tissues are more plentiful in minor than in major salivary glands. In the latter, they comprise no more than 10% of tumors. In both sites, however, their clinical course is characterized by local aggressiveness, recurrences, and a relatively torpid and protracted course, eventually leading to death. The clinicopathologic aspects of these two lesions form the major part of this report. Their behavior is contrasted with that of the two other lesions presented: heterotopic salivary tissue, which is seldom the site of neoplasia; and necrotizing sialometaplasia, a self-limited disorder that simulates malignancy both clinically and histopathologically."}
{"id": "PMID:227823", "title": "Synovial sarcoma in a dog.", "content": "A 6.5-year-old, female Saint Bernard had a slowly growing tumor of the right tibiotarsal joint. Radiographically, bone surrounding the tumor was not involved. Subtotal surgical resection was undertaken. The tumor was classified histologically as a synovioma. Within 6 months, the tumor recurred locally and invaded the soft tissue proximal to the tibiotarsal joint. Eighteen months after initial examination, there was widespread right tibial invasion and pulmonary metastasis. The dog was euthanatized. The final histopathologic diagnosis was synovial sarcoma.", "contents": "Synovial sarcoma in a dog. A 6.5-year-old, female Saint Bernard had a slowly growing tumor of the right tibiotarsal joint. Radiographically, bone surrounding the tumor was not involved. Subtotal surgical resection was undertaken. The tumor was classified histologically as a synovioma. Within 6 months, the tumor recurred locally and invaded the soft tissue proximal to the tibiotarsal joint. Eighteen months after initial examination, there was widespread right tibial invasion and pulmonary metastasis. The dog was euthanatized. The final histopathologic diagnosis was synovial sarcoma."}
{"id": "PMID:227825", "title": "Postnatal changes in the distribution of lipid droplets within the liver lobule of the mouse.", "content": "The changes in the distribution of lipid droplets in the liver lobule were studied during the postnatal development of the mouse. At birth, and 1 day after birth, lipid droplets were evenly distributed throughout the lobule. A slightly uneven distribution of the droplets, more in centrilobular areas, appeared 2 days after birth. After this the difference in the number of droplets between the cells of the centrilobular and periportal areas became progressively more marked reaching a maximum by 17 days of age, and then decreasing to the adult level between 21 and 24 days. Thus, heterogeneity among hepatocytes with respect to lipid content is not present in newborn mice but develops gradually during the postnatal development.", "contents": "Postnatal changes in the distribution of lipid droplets within the liver lobule of the mouse. The changes in the distribution of lipid droplets in the liver lobule were studied during the postnatal development of the mouse. At birth, and 1 day after birth, lipid droplets were evenly distributed throughout the lobule. A slightly uneven distribution of the droplets, more in centrilobular areas, appeared 2 days after birth. After this the difference in the number of droplets between the cells of the centrilobular and periportal areas became progressively more marked reaching a maximum by 17 days of age, and then decreasing to the adult level between 21 and 24 days. Thus, heterogeneity among hepatocytes with respect to lipid content is not present in newborn mice but develops gradually during the postnatal development."}
{"id": "PMID:227829", "title": "In vitro combination of mecillinam with cephradine or amoxycillin for organisms resistant to single agents.", "content": "Of 36 multi-resistant Gram-negative bacilli isolated from different cases of urinary tract infection, 18 strains of Escherichia coli, klebsiella, enterobacter, proteus, providencia and serratia with the exception of Acinetobacter species showed synergy when mecillinam was combined with cephradine or amoxycillin in the ratio of 1:1. Combination with cephradine was synergistic on sixteen occasions and amoxycillin on six. Synergy, which might have clinical relevance, was demonstrated only when the test organism was either fully or moderately sensitive to one of the two antibiotics combined but not when resistant to both.", "contents": "In vitro combination of mecillinam with cephradine or amoxycillin for organisms resistant to single agents. Of 36 multi-resistant Gram-negative bacilli isolated from different cases of urinary tract infection, 18 strains of Escherichia coli, klebsiella, enterobacter, proteus, providencia and serratia with the exception of Acinetobacter species showed synergy when mecillinam was combined with cephradine or amoxycillin in the ratio of 1:1. Combination with cephradine was synergistic on sixteen occasions and amoxycillin on six. Synergy, which might have clinical relevance, was demonstrated only when the test organism was either fully or moderately sensitive to one of the two antibiotics combined but not when resistant to both."}
{"id": "PMID:227830", "title": "Rapid methods for differentiating reactivated from residual phosphatase in milk and cream: collaborative study.", "content": "Three methods for differentiating reactivated from residual phosphatase in milk and cream were collaboratively tested using both magnesium acetate and magnesium chloride for reactivating phosphatase. The methods evaluated were the modified Scharer rapid test, the rapid colorimetric test, and the Rutgers method. Nine collaborators tested 6 unknown milk samples containing reactivated and/or residual phosphatase, and 16 collaborators tested 6 unknown cream samples containing reactivated and/or residual phosphatase. Results indicated that use of magnesium acetate in place of magnesium chloride for reactivating phosphatase improved test results. Visual tests (modified Scharer rapid and Rutgers) predicted correct results when the samples contained high levels of reactivated or residual phosphatase. In borderline cases where the reactivated phosphatase contents of the undiluted control sample and the diluted sample containing Mg were very close, the test results of the visual methods were significantly different from 100% correct results at the alpha=0.05 level. Use of a photoelectric colorimeter or its equivalent for measuring the absorbance in conjunction with the modified Scharer rapid test improved results considerably. The modified Scharer rapid test was adopted official first action.", "contents": "Rapid methods for differentiating reactivated from residual phosphatase in milk and cream: collaborative study. Three methods for differentiating reactivated from residual phosphatase in milk and cream were collaboratively tested using both magnesium acetate and magnesium chloride for reactivating phosphatase. The methods evaluated were the modified Scharer rapid test, the rapid colorimetric test, and the Rutgers method. Nine collaborators tested 6 unknown milk samples containing reactivated and/or residual phosphatase, and 16 collaborators tested 6 unknown cream samples containing reactivated and/or residual phosphatase. Results indicated that use of magnesium acetate in place of magnesium chloride for reactivating phosphatase improved test results. Visual tests (modified Scharer rapid and Rutgers) predicted correct results when the samples contained high levels of reactivated or residual phosphatase. In borderline cases where the reactivated phosphatase contents of the undiluted control sample and the diluted sample containing Mg were very close, the test results of the visual methods were significantly different from 100% correct results at the alpha=0.05 level. Use of a photoelectric colorimeter or its equivalent for measuring the absorbance in conjunction with the modified Scharer rapid test improved results considerably. The modified Scharer rapid test was adopted official first action."}
{"id": "PMID:227832", "title": "Mutant single-strand binding protein of Escherichia coli: genetic and physiological characterization.", "content": "A mutation in the Escherichia coli gene for single-strand binding protein results in temperature-sensitive deoxyribonucleic acid replication (R. R. Meyer, J. Glassberg, and A. Kornberg, Proc. Natl. Acad. Sci. U.S.A. 76:1702-1705, 1979). The mutant (ssb-1) is also more sensitive to ultraviolet irradiation and about one-fifth as active in recombination. Single-strand binding protein is thus implicated in repair and recombination as well as in replication. The mutation in ssb is located between uvrA and melA at 90.8 min on the genetic map. The ssb gene appears to be allelic with lexC, a gene with a proposed role in regulating inducible deoxyribonucleic acid repair.", "contents": "Mutant single-strand binding protein of Escherichia coli: genetic and physiological characterization. A mutation in the Escherichia coli gene for single-strand binding protein results in temperature-sensitive deoxyribonucleic acid replication (R. R. Meyer, J. Glassberg, and A. Kornberg, Proc. Natl. Acad. Sci. U.S.A. 76:1702-1705, 1979). The mutant (ssb-1) is also more sensitive to ultraviolet irradiation and about one-fifth as active in recombination. Single-strand binding protein is thus implicated in repair and recombination as well as in replication. The mutation in ssb is located between uvrA and melA at 90.8 min on the genetic map. The ssb gene appears to be allelic with lexC, a gene with a proposed role in regulating inducible deoxyribonucleic acid repair."}
{"id": "PMID:227833", "title": "Deoxyribonucleic acid in Nitrobacter carboxysomes.", "content": "Carboxysomes were isolated from Nitrobacter winogradskyi and Nitrobacter agilis. The icosahedral particles contained double-stranded deoxyribonucleic acid (DNA). In the presence of ethidium bromide and cesium chloride, the particle-bound DNA had a buoyant density of rho 25 = 1.701 g/cm3. Electron microscopy revealed the DNA to be a 14-micron circular molecule.", "contents": "Deoxyribonucleic acid in Nitrobacter carboxysomes. Carboxysomes were isolated from Nitrobacter winogradskyi and Nitrobacter agilis. The icosahedral particles contained double-stranded deoxyribonucleic acid (DNA). In the presence of ethidium bromide and cesium chloride, the particle-bound DNA had a buoyant density of rho 25 = 1.701 g/cm3. Electron microscopy revealed the DNA to be a 14-micron circular molecule."}
{"id": "PMID:227834", "title": "Deoxyribonucleic acid and outer membrane: binding to outer membrane involves a specific protein.", "content": "The binding of deoxyribonucleic acid (DNA) to the outer membrane of Escherichia coli was examined. The amount of DNA found to be bound to outer membrane was low and was estimated to be about 0.4% of the total DNA. Treatment of cells with chloramphenicol or rifampin caused a disassociation of the apparent DNA-outer membrane complex. The results presented here suggest that the binding between membrane and DNA is specific and involves a membrane protein having a molecular weight of 13,000.", "contents": "Deoxyribonucleic acid and outer membrane: binding to outer membrane involves a specific protein. The binding of deoxyribonucleic acid (DNA) to the outer membrane of Escherichia coli was examined. The amount of DNA found to be bound to outer membrane was low and was estimated to be about 0.4% of the total DNA. Treatment of cells with chloramphenicol or rifampin caused a disassociation of the apparent DNA-outer membrane complex. The results presented here suggest that the binding between membrane and DNA is specific and involves a membrane protein having a molecular weight of 13,000."}
{"id": "PMID:227835", "title": "Deoxyribonucleic acid and outer membrane: strains diploid for the oriC region show elevated levels of deoxyribonucleic acid-binding protein and evidence for specific binding of the oriC region to outer membrane.", "content": "We have recently reported that part of the chromosomal deoxyribonucleic acid (DNA) of Escherichia coli is associated with the outer membrane fraction and that an outer membrane protein having a molecular weight of 31,000 probably is involved in this association (H. Wolf-Watz and A. Norqvist, J. Bacteriol. 140:43-49, 1979). We have now found that F' merodiploid strains containing two copies of the DNA between bglB and ilv have increased levels of this protein and an increased amount of DNA in their outer membranes. Increased levels of the protein are also found when lambda asn  phage, containing at 1.5-megadalton fragment of DNA located to the right of the uncA uncB genes but to the left of oriC, are induced. It therefore seems that this 1.5-megadalton fragment of DNA either codes for or binds to the 31,000-dalton outer membrane protein. Hybridization studies utilizing DNA found to be bound to outer membrane and DNA isolated from a specialized transducing phage lambda asn 132 revealed that at least 5 to 10% of outer membrane DNA has a DNA sequence homologous with a chromosomal segment carried by this oriC-containing phage.", "contents": "Deoxyribonucleic acid and outer membrane: strains diploid for the oriC region show elevated levels of deoxyribonucleic acid-binding protein and evidence for specific binding of the oriC region to outer membrane. We have recently reported that part of the chromosomal deoxyribonucleic acid (DNA) of Escherichia coli is associated with the outer membrane fraction and that an outer membrane protein having a molecular weight of 31,000 probably is involved in this association (H. Wolf-Watz and A. Norqvist, J. Bacteriol. 140:43-49, 1979). We have now found that F' merodiploid strains containing two copies of the DNA between bglB and ilv have increased levels of this protein and an increased amount of DNA in their outer membranes. Increased levels of the protein are also found when lambda asn  phage, containing at 1.5-megadalton fragment of DNA located to the right of the uncA uncB genes but to the left of oriC, are induced. It therefore seems that this 1.5-megadalton fragment of DNA either codes for or binds to the 31,000-dalton outer membrane protein. Hybridization studies utilizing DNA found to be bound to outer membrane and DNA isolated from a specialized transducing phage lambda asn 132 revealed that at least 5 to 10% of outer membrane DNA has a DNA sequence homologous with a chromosomal segment carried by this oriC-containing phage."}
{"id": "PMID:227836", "title": "Spore lytic enzyme released from Clostridium perfringens spores during germination.", "content": "The exudate of fully germinated spores of Clostridium perfringens was found to contain a large amount of a spore lytic enzyme which acted directly on alkali-treated spores of the organism to cause germination. Although no detectable amount of the enzyme was found in dormant spores during germination in a KCl medium, the enzyme was produced rapidly and released into the medium. The optimal conditions for enzyme activity were pH 6.0 and 45 degrees C. Maximum activity occurred in the presence of various univalent cations at a concentration of 50 mM. The enzyme was readily inactivated by several sulfhydryl reagents. A strong reducing condition was generated in the ionic germination of the spores, a minimum Eh level of -350 mV being reached 30 min after initiation of germination. Furthermore, adenosine triphosphate-dependent pyruvate:ferredoxin oxidoreductase (EC 1.2.7.1) was identified in both dorman and germinated spores. The relationship between the release of active enzyme and the generation of reducing conditions during germination is discussed.", "contents": "Spore lytic enzyme released from Clostridium perfringens spores during germination. The exudate of fully germinated spores of Clostridium perfringens was found to contain a large amount of a spore lytic enzyme which acted directly on alkali-treated spores of the organism to cause germination. Although no detectable amount of the enzyme was found in dormant spores during germination in a KCl medium, the enzyme was produced rapidly and released into the medium. The optimal conditions for enzyme activity were pH 6.0 and 45 degrees C. Maximum activity occurred in the presence of various univalent cations at a concentration of 50 mM. The enzyme was readily inactivated by several sulfhydryl reagents. A strong reducing condition was generated in the ionic germination of the spores, a minimum Eh level of -350 mV being reached 30 min after initiation of germination. Furthermore, adenosine triphosphate-dependent pyruvate:ferredoxin oxidoreductase (EC 1.2.7.1) was identified in both dorman and germinated spores. The relationship between the release of active enzyme and the generation of reducing conditions during germination is discussed."}
{"id": "PMID:227837", "title": "A new gene of Escherichia coli K-12 whose product participates in T4 bacteriophage late gene expression: interaction of lit with the T4-induced polynucleotide 5'-kinase 3'-phosphatase.", "content": "We isolated five Escherichia coli mutants deficient in their ability to support the late (replication-coupled) gene expression of T4 bacteriophage at 30 degrees C. These mutants, which we call Lit mutants, define at least one novel gene at 25 min on the E. coli map. They were selected in an attempt to obtain mutants which restrict the growth of T4 mutants deficient in polynucleotide 5'-kinase 3'-phosphatase but not that of wild-type T4 at 37 degrees C. Some of the mutants do have these phenotypes under some conditions. Studies of the block in T4 development in some of the E. coli mutants suggest that Lit mutants are affected in a gene product involved in the metabolism of deoxyribonucleic acid nicks or single-strand gaps. None of the Lit mutants is deficient in the major, bacterial, 3'-phosphatase activity in crude extracts.", "contents": "A new gene of Escherichia coli K-12 whose product participates in T4 bacteriophage late gene expression: interaction of lit with the T4-induced polynucleotide 5'-kinase 3'-phosphatase. We isolated five Escherichia coli mutants deficient in their ability to support the late (replication-coupled) gene expression of T4 bacteriophage at 30 degrees C. These mutants, which we call Lit mutants, define at least one novel gene at 25 min on the E. coli map. They were selected in an attempt to obtain mutants which restrict the growth of T4 mutants deficient in polynucleotide 5'-kinase 3'-phosphatase but not that of wild-type T4 at 37 degrees C. Some of the mutants do have these phenotypes under some conditions. Studies of the block in T4 development in some of the E. coli mutants suggest that Lit mutants are affected in a gene product involved in the metabolism of deoxyribonucleic acid nicks or single-strand gaps. None of the Lit mutants is deficient in the major, bacterial, 3'-phosphatase activity in crude extracts."}
{"id": "PMID:227838", "title": "Cyclic adenosine 3',5'-monophosphate regulation of the bacteriophage T6/colicin K receptor in Escherichia coli.", "content": "Mutant strains of Escherichia coli unable to synthesize cyclic adenosine 3',5'-monophosphate (cAMP) or the cyclic adenosine monophosphate receptor protein (CRP) were more resistant than wild-type cells to infection by bacteriophage T6. This resistance was found to be associated with the decreased production of specific T6 receptor protein (also the colicin K receptor) located in the outer membrane protein fraction of these cells. Transcription of this particular outer membrane protein was regulated by the cAMP-CRP complex. A novel affinity technique coupled with sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used in these investigations.", "contents": "Cyclic adenosine 3',5'-monophosphate regulation of the bacteriophage T6/colicin K receptor in Escherichia coli. Mutant strains of Escherichia coli unable to synthesize cyclic adenosine 3',5'-monophosphate (cAMP) or the cyclic adenosine monophosphate receptor protein (CRP) were more resistant than wild-type cells to infection by bacteriophage T6. This resistance was found to be associated with the decreased production of specific T6 receptor protein (also the colicin K receptor) located in the outer membrane protein fraction of these cells. Transcription of this particular outer membrane protein was regulated by the cAMP-CRP complex. A novel affinity technique coupled with sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used in these investigations."}
{"id": "PMID:227839", "title": "Production and excretion of cloacin DF13 by Escherichia coli harboring plasmid CloDF13.", "content": "The production and the mechanism of excretion of cloacin DF13 were investigated in noninduced and mitomycin C-induced cell cultures. A mitomycin C concentration was selected which did not cause lysis of cloacinogenic cells, but at the same time induced a maximal production of cloacin DF13. Native cloacin DF13, possessing killing activity, was first released into the cytoplasm. Shortly thereafter, the bacteriocin was transported through the cytoplasmic membrane and accumulated in the periplasm. Finally, cloacin DF13 was excreted into the culture medium. A small amount of cloacin DF13 remained associated with the cell surface. Producing cells did not become permeable for the cytoplasmic enzyme beta-galactosidase. Apparently the cloacin DF13 leaves the producing cells by an excretion process which is not similar to the mechanism proposed for bacterial secretory proteins. The processes of excretion by producing cells and of uptake by susceptible cells were also not identical because mutant cloacin DF13, which was not transported through the outer membrane into susceptible cells, was excreted like the wild-type cloacin DF13. The composition of the culture medium greatly affected production of cloacin DF13. The presence of sugars known to cause catabolite repression not only inhibited the production but also strongly reduced the excretion of cloacin DF13 into the culture medium.", "contents": "Production and excretion of cloacin DF13 by Escherichia coli harboring plasmid CloDF13. The production and the mechanism of excretion of cloacin DF13 were investigated in noninduced and mitomycin C-induced cell cultures. A mitomycin C concentration was selected which did not cause lysis of cloacinogenic cells, but at the same time induced a maximal production of cloacin DF13. Native cloacin DF13, possessing killing activity, was first released into the cytoplasm. Shortly thereafter, the bacteriocin was transported through the cytoplasmic membrane and accumulated in the periplasm. Finally, cloacin DF13 was excreted into the culture medium. A small amount of cloacin DF13 remained associated with the cell surface. Producing cells did not become permeable for the cytoplasmic enzyme beta-galactosidase. Apparently the cloacin DF13 leaves the producing cells by an excretion process which is not similar to the mechanism proposed for bacterial secretory proteins. The processes of excretion by producing cells and of uptake by susceptible cells were also not identical because mutant cloacin DF13, which was not transported through the outer membrane into susceptible cells, was excreted like the wild-type cloacin DF13. The composition of the culture medium greatly affected production of cloacin DF13. The presence of sugars known to cause catabolite repression not only inhibited the production but also strongly reduced the excretion of cloacin DF13 into the culture medium."}
{"id": "PMID:227840", "title": "Escherichia coli mutants thermosensitive for deoxyribonucleic acid gyrase subunit A: effects on deoxyribonucleic acid replication, transcription, and bacteriophage growth.", "content": "Temperature-sensitive nalA mutants of Escherichia coli have been used to investigate the structure and functions of deoxyribonucleic acid (DNA) gyrase. Extracts of one such mutant (nalA43) had thermosensitive DNA gyrase subunit A activity but normal gyrase subunit B activity, proving definitively that nalA is the structural gene for subunit A. Extracts of a second nalA (Ts) mutant (nalA45) had a 50-fold deficiency of gyrase subunit A activity. The residual DNA supertwisting was catalyzed by the mutant DNA gyrase rather than by a novel supertwisting enzyme. The nalA45(Ts) extract was also deficient in the nalidixic acid target, which is defined as the protein necessary to confer drug sensitivity to in vitro DNA replication directed by a nalidixic acid-resistant mutant extract. Thus, gyrase subunit A and the nalidixic acid target are one and the same protein, the nalA gene product. Shift of the nalA43(Ts) mutant to a nonpermissive temperature resulted in a precipitous decline in the rate of [(3)H]thymidine incorporation, demonstrating an obligatory role of the nalA gene product in DNA replication. The rates of incorporation of [(3)H]uridine pulses and continuously administered [(3)H]uracil were quickly reduced approximately twofold upon temperature shift of the nalA43(Ts) mutant, and therefore some but not all transcription requires the nalA gene product. The thermosensitive growth of bacteriophages phiX174 and T4 in the nalA43(Ts) host shows that these phages depend on the host nalA gene product. In contrast, the growth of phage T7 was strongly inhibited by nalidixic acid but essentially unaffected by the nalA43(Ts) mutation. The inhibition of T7 growth by nalidixic acid was, however, eliminated by temperature inactivation of the nal43 gene product. Therefore, nalidixic acid may block T7 growth by a corruption rather than a simple elimination of the nalidixic acid target. Possible mechanisms for such a corruption are considered, and their relevance to the puzzling dominance of drug sensitivity is discussed.", "contents": "Escherichia coli mutants thermosensitive for deoxyribonucleic acid gyrase subunit A: effects on deoxyribonucleic acid replication, transcription, and bacteriophage growth. Temperature-sensitive nalA mutants of Escherichia coli have been used to investigate the structure and functions of deoxyribonucleic acid (DNA) gyrase. Extracts of one such mutant (nalA43) had thermosensitive DNA gyrase subunit A activity but normal gyrase subunit B activity, proving definitively that nalA is the structural gene for subunit A. Extracts of a second nalA (Ts) mutant (nalA45) had a 50-fold deficiency of gyrase subunit A activity. The residual DNA supertwisting was catalyzed by the mutant DNA gyrase rather than by a novel supertwisting enzyme. The nalA45(Ts) extract was also deficient in the nalidixic acid target, which is defined as the protein necessary to confer drug sensitivity to in vitro DNA replication directed by a nalidixic acid-resistant mutant extract. Thus, gyrase subunit A and the nalidixic acid target are one and the same protein, the nalA gene product. Shift of the nalA43(Ts) mutant to a nonpermissive temperature resulted in a precipitous decline in the rate of [(3)H]thymidine incorporation, demonstrating an obligatory role of the nalA gene product in DNA replication. The rates of incorporation of [(3)H]uridine pulses and continuously administered [(3)H]uracil were quickly reduced approximately twofold upon temperature shift of the nalA43(Ts) mutant, and therefore some but not all transcription requires the nalA gene product. The thermosensitive growth of bacteriophages phiX174 and T4 in the nalA43(Ts) host shows that these phages depend on the host nalA gene product. In contrast, the growth of phage T7 was strongly inhibited by nalidixic acid but essentially unaffected by the nalA43(Ts) mutation. The inhibition of T7 growth by nalidixic acid was, however, eliminated by temperature inactivation of the nal43 gene product. Therefore, nalidixic acid may block T7 growth by a corruption rather than a simple elimination of the nalidixic acid target. Possible mechanisms for such a corruption are considered, and their relevance to the puzzling dominance of drug sensitivity is discussed."}
{"id": "PMID:227841", "title": "Transport of cyclic adenosine 3',5'-monophosphate across Escherichia coli vesicle membranes.", "content": "The uptake and efflux of cyclic adenosine 3',5'-monophosphate (3',5'-cAMP) by Escherichia coli membrane vesicles were studied. Metabolic energy was not required for the uptake process and was found to actually decrease the amount of 3',5'-cAMP found in the vesicles. 3',5'-cAMP uptake exhibits saturation kinetics (Km = 10 mM, Vmax = 2.8 nmol/mg of protein per min) and was competitively inhibited by a number of 3',5'-cAMP analogs. The uptake of 3',5'-cAMP was found to be sharply affected by a membrane phase transition. The excretion of 3',5'-cAMP was studied by using everted membrane vesicles. Efflux in this system was dependent upon metabolic energy and was reduced or abolished by uncouplers. Different energy sources powered efflux at different rates, showing a relationship between the degree of membrane energization and rate of excretion of 3',5'-cAMP. The efflux process also displayed saturation kinetics (Km = 10.0 mM, Vmax = 0.98 nmol/mg of protein per min) and was competitively inhibited by the same 3',5'-cAMP analogs and to the same degree as was the uptake process. 3',5'-cAMP was found to be chemically unaltered by both the uptake and excretion processes. These data are interpreted as showing that the uptake and excretion of 3',5'-cAMP in E. coli membrane vesicles are carrier-mediated phenomena, possibly employing the same carrier system. Uptake is by facilitated diffusion whereas efflux is via an energy-dependent, active transport process. Evidence is presented showing that cells can regulate the number of 3',5'-cAMP transport carriers. The rate of 3',5'-cAMP excretion is possibly regulated by both the degree of membrane energization and the number of carriers present per cells.", "contents": "Transport of cyclic adenosine 3',5'-monophosphate across Escherichia coli vesicle membranes. The uptake and efflux of cyclic adenosine 3',5'-monophosphate (3',5'-cAMP) by Escherichia coli membrane vesicles were studied. Metabolic energy was not required for the uptake process and was found to actually decrease the amount of 3',5'-cAMP found in the vesicles. 3',5'-cAMP uptake exhibits saturation kinetics (Km = 10 mM, Vmax = 2.8 nmol/mg of protein per min) and was competitively inhibited by a number of 3',5'-cAMP analogs. The uptake of 3',5'-cAMP was found to be sharply affected by a membrane phase transition. The excretion of 3',5'-cAMP was studied by using everted membrane vesicles. Efflux in this system was dependent upon metabolic energy and was reduced or abolished by uncouplers. Different energy sources powered efflux at different rates, showing a relationship between the degree of membrane energization and rate of excretion of 3',5'-cAMP. The efflux process also displayed saturation kinetics (Km = 10.0 mM, Vmax = 0.98 nmol/mg of protein per min) and was competitively inhibited by the same 3',5'-cAMP analogs and to the same degree as was the uptake process. 3',5'-cAMP was found to be chemically unaltered by both the uptake and excretion processes. These data are interpreted as showing that the uptake and excretion of 3',5'-cAMP in E. coli membrane vesicles are carrier-mediated phenomena, possibly employing the same carrier system. Uptake is by facilitated diffusion whereas efflux is via an energy-dependent, active transport process. Evidence is presented showing that cells can regulate the number of 3',5'-cAMP transport carriers. The rate of 3',5'-cAMP excretion is possibly regulated by both the degree of membrane energization and the number of carriers present per cells."}
{"id": "PMID:227842", "title": "Regulation of phosphate accumulation in the unicellular cyanobacterium Synechococcus.", "content": "The phosphorus contents of acid-soluble pools, lipid, ribonucleic acid, and acid-insoluble polyphosphate were lowered in Synechococcus in proportion to the reduction in growth rate in phosphate-limited but not in nitrate-limited continuous culture. Phosphorus in these cell fractions was lost proportionately during progressive phosphate starvation of batch cultures. Acid-insoluble polyphosphate was always present in all cultural conditions to about 10% of total cell phosphorus and did not turn over during balanced exponential growth. Extensive polyphosphate formation occurred transiently when phosphate was given to cells which had been phosphate limited. This material was broken down after 8 h even in the presence of excess external orthophosphate, and its phosphorus was transferred into other cell fractions, notably ribonucleic acid. Phosphate uptake kinetics indicated an invariant apparent K(m) of about 0.5 muM, but V(max) was 40 to 50 times greater in cells from phosphate-limited cultures than in cells from nitrate-limited or balanced batch cultures. Over 90% of the phosphate taken up within the first 30 s at 15 degrees C was recovered as orthophosphate. The uptake process is highly specific, since neither phosphate entry nor growth was affected by a 100-fold excess of arsenate. The activity of polyphosphate synthetase in cell extracts increased at least 20-fold during phosphate starvation or in phosphate-restricted growth, but polyphosphatase activity was little changed by different growth conditions. The findings suggest that derepression of the phosphate transport and polyphosphate-synthesizing systems as well as alkaline phosphatase occurs in phosphate shortage, but that the breakdown of polyphosphate in this organism is regulated by modulation of existing enzyme activity.", "contents": "Regulation of phosphate accumulation in the unicellular cyanobacterium Synechococcus. The phosphorus contents of acid-soluble pools, lipid, ribonucleic acid, and acid-insoluble polyphosphate were lowered in Synechococcus in proportion to the reduction in growth rate in phosphate-limited but not in nitrate-limited continuous culture. Phosphorus in these cell fractions was lost proportionately during progressive phosphate starvation of batch cultures. Acid-insoluble polyphosphate was always present in all cultural conditions to about 10% of total cell phosphorus and did not turn over during balanced exponential growth. Extensive polyphosphate formation occurred transiently when phosphate was given to cells which had been phosphate limited. This material was broken down after 8 h even in the presence of excess external orthophosphate, and its phosphorus was transferred into other cell fractions, notably ribonucleic acid. Phosphate uptake kinetics indicated an invariant apparent K(m) of about 0.5 muM, but V(max) was 40 to 50 times greater in cells from phosphate-limited cultures than in cells from nitrate-limited or balanced batch cultures. Over 90% of the phosphate taken up within the first 30 s at 15 degrees C was recovered as orthophosphate. The uptake process is highly specific, since neither phosphate entry nor growth was affected by a 100-fold excess of arsenate. The activity of polyphosphate synthetase in cell extracts increased at least 20-fold during phosphate starvation or in phosphate-restricted growth, but polyphosphatase activity was little changed by different growth conditions. The findings suggest that derepression of the phosphate transport and polyphosphate-synthesizing systems as well as alkaline phosphatase occurs in phosphate shortage, but that the breakdown of polyphosphate in this organism is regulated by modulation of existing enzyme activity."}
{"id": "PMID:227843", "title": "Binding of ouabain to Na+, K+-dependent ATPase during the ATPase reaction. Evidence for a dimer structure of the ATPase.", "content": "Na+, K+-dependent ATPase [EC 3.6.1.3] was purified from porcine kidney by the method of Lane et al. [(1973) J. Biol. Chem. 248, 7197-7200] with slight modifications [Yamaguchi, M. & Tonomura, Y., (1979) J. Biochem. 86, 509-523]. The amounts of a phosphorylated intermediate (EP) and ouabain bound to the enzyme during the ATPase reaction were measured in 2.1 mM MgCl2 and various concentrations of NaCl and KCl at pH 7.5 and 20 degrees C. In presence of NaCl and the absence of KCl, the molar ratio of the amounts of EP and bound ouabain was 1 : 2. In the presence of both NaCl and KCl, it was 1 : 1. In both cases, the amount of bound ouabain was equal to that of EP in the absence of ouabain. These findings suggest that the functional unit of the transport ATPase is a dimer.", "contents": "Binding of ouabain to Na+, K+-dependent ATPase during the ATPase reaction. Evidence for a dimer structure of the ATPase. Na+, K+-dependent ATPase [EC 3.6.1.3] was purified from porcine kidney by the method of Lane et al. [(1973) J. Biol. Chem. 248, 7197-7200] with slight modifications [Yamaguchi, M. & Tonomura, Y., (1979) J. Biochem. 86, 509-523]. The amounts of a phosphorylated intermediate (EP) and ouabain bound to the enzyme during the ATPase reaction were measured in 2.1 mM MgCl2 and various concentrations of NaCl and KCl at pH 7.5 and 20 degrees C. In presence of NaCl and the absence of KCl, the molar ratio of the amounts of EP and bound ouabain was 1 : 2. In the presence of both NaCl and KCl, it was 1 : 1. In both cases, the amount of bound ouabain was equal to that of EP in the absence of ouabain. These findings suggest that the functional unit of the transport ATPase is a dimer."}
{"id": "PMID:227844", "title": "Effect of removal of a salt-bridge on the oxygen binding properties and the electronic structure of heme in cobalt-iron hybrid hemoglobin.", "content": "In order to clarify the role of salt-bridges in hemoglobin, the oxygen equilibrium curves and electron paramagnetic resonance (EPR) spectra of cobalt-iron hybrid hemoglobins were determined. The EPR spectra of deoxy alpha(Co)2 beta(Fe)2 could be interpreted as a mixture of two distinct paramagnetic species: one showed a maximum of the first derivative spectrum at g = 2.39 and the other at g = 2.33. The oxygen equilibrium curves of the hybrid indicated that the former is assignable to the T structure and the latter to the R structure. The cooperativity of oxygen binding of alpha(Co)2 beta(Fe)2 exhibited a maximum at g = 2.33, which is characteristic of the R structure, regardless of the pH. Addition of inositol hexaphosphate (IHP) to des-Arg alpha(Co)2 beta(Fe)2 restored the cooperativity of oxygen binding, which implies that the deoxygenated form of des-Arg alpha(Co)2 beta(Fe)2 is converted to the T structure upon addition of IHP. However, the EPR signal at g = 2.39 was not restored upon conversion to the T structure by addition of IHP. It is therefore concluded that the EPR spectrum of the deoxy alpha(Co) subunit depends both on the quaternary structure and on the localized strain at the heme.", "contents": "Effect of removal of a salt-bridge on the oxygen binding properties and the electronic structure of heme in cobalt-iron hybrid hemoglobin. In order to clarify the role of salt-bridges in hemoglobin, the oxygen equilibrium curves and electron paramagnetic resonance (EPR) spectra of cobalt-iron hybrid hemoglobins were determined. The EPR spectra of deoxy alpha(Co)2 beta(Fe)2 could be interpreted as a mixture of two distinct paramagnetic species: one showed a maximum of the first derivative spectrum at g = 2.39 and the other at g = 2.33. The oxygen equilibrium curves of the hybrid indicated that the former is assignable to the T structure and the latter to the R structure. The cooperativity of oxygen binding of alpha(Co)2 beta(Fe)2 exhibited a maximum at g = 2.33, which is characteristic of the R structure, regardless of the pH. Addition of inositol hexaphosphate (IHP) to des-Arg alpha(Co)2 beta(Fe)2 restored the cooperativity of oxygen binding, which implies that the deoxygenated form of des-Arg alpha(Co)2 beta(Fe)2 is converted to the T structure upon addition of IHP. However, the EPR signal at g = 2.39 was not restored upon conversion to the T structure by addition of IHP. It is therefore concluded that the EPR spectrum of the deoxy alpha(Co) subunit depends both on the quaternary structure and on the localized strain at the heme."}
{"id": "PMID:227845", "title": "Highly purified hydroxylamine oxidoreductase derived from Nitrosomonas europaea. Some physicochemical and enzymatic properties.", "content": "Hydroxylamine oxidoreductase [EC 1.7.3.4] of Nitrosomonas europaea was purified to an electrophoretically homogeneous state and some of its properties were studied. The molecular weight of the enzyme as determined by gel filtration on Sephadex G150 and by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate is 175,000-180,000, while the minimum molecular weight per heme determined from the dry weight and heme content is 17,500. The enzyme is a C-type cytochrome; its reduced form shows absorption peaks at 418 (gamma peak), 521 (beta peak), 553 (alpha peak), and 460 nm (due to an unidentified chromophore). Although the alpha peak at 553 nm has a shoulder at 559 nm, the enzyme does not posses protoheme or a cytochrome b subunit. It seems likely that the enzyme molecule possess heme c molecules in different states. The enzyme reacts rapidly with various eukaryotic cytochromes c, but does not react with \"bacterial-type\" cytochromes c. Although the enzyme does not react with cytochrome c-552 (N. europaea), another C-type cytochrome of the organism, cytochrome c-554 (N. europaea) acts as an electron acceptor for the enzyme.", "contents": "Highly purified hydroxylamine oxidoreductase derived from Nitrosomonas europaea. Some physicochemical and enzymatic properties. Hydroxylamine oxidoreductase [EC 1.7.3.4] of Nitrosomonas europaea was purified to an electrophoretically homogeneous state and some of its properties were studied. The molecular weight of the enzyme as determined by gel filtration on Sephadex G150 and by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate is 175,000-180,000, while the minimum molecular weight per heme determined from the dry weight and heme content is 17,500. The enzyme is a C-type cytochrome; its reduced form shows absorption peaks at 418 (gamma peak), 521 (beta peak), 553 (alpha peak), and 460 nm (due to an unidentified chromophore). Although the alpha peak at 553 nm has a shoulder at 559 nm, the enzyme does not posses protoheme or a cytochrome b subunit. It seems likely that the enzyme molecule possess heme c molecules in different states. The enzyme reacts rapidly with various eukaryotic cytochromes c, but does not react with \"bacterial-type\" cytochromes c. Although the enzyme does not react with cytochrome c-552 (N. europaea), another C-type cytochrome of the organism, cytochrome c-554 (N. europaea) acts as an electron acceptor for the enzyme."}
{"id": "PMID:227846", "title": "Probable sites of action of cyclic adenosine 3',5'-monophosphate in the induction of phosphodiesterase in Dictyostelium discoideum.", "content": "The sites of action cyclic adenosine 3',5'-monophosphate (cAMP) in phosphodiesterase [EC 3.1.4.17] induction in Dictyostelium discoideum were studied. When cAMP was added to the cell suspension from the start of the incubation, the effect of the cyclic nucleotide on the cellular enzyme-induction did not appear for 30 min, then occurred abruptly. From experiments on the addition of cAMP to the cell incubation mixture at various times, preparations for the synthesis of the enzyme appear to occur during the period from 20 min to 30 min after the start of the incubation. After the addition of cycloheximide at 30 min, the enzyme was degraded very rapidly. The half-life of phosphodiesterase was roughly 21 min in the presence of cAMP, and 12 min in its absence. The degradation rates became approximately the same on removing cAMP. When daunomycin and actinomycin D were added to cells previously stimulated with cAMP, phosphodiesterase was still synthesized at a higher rate than in cells not pretreated with cAMP. These results suggest that cAMP acts at two sites at least, i.e., on enzyme synthesis at the transcription level, and in suppressing the degradation of phosphodiesterase.", "contents": "Probable sites of action of cyclic adenosine 3',5'-monophosphate in the induction of phosphodiesterase in Dictyostelium discoideum. The sites of action cyclic adenosine 3',5'-monophosphate (cAMP) in phosphodiesterase [EC 3.1.4.17] induction in Dictyostelium discoideum were studied. When cAMP was added to the cell suspension from the start of the incubation, the effect of the cyclic nucleotide on the cellular enzyme-induction did not appear for 30 min, then occurred abruptly. From experiments on the addition of cAMP to the cell incubation mixture at various times, preparations for the synthesis of the enzyme appear to occur during the period from 20 min to 30 min after the start of the incubation. After the addition of cycloheximide at 30 min, the enzyme was degraded very rapidly. The half-life of phosphodiesterase was roughly 21 min in the presence of cAMP, and 12 min in its absence. The degradation rates became approximately the same on removing cAMP. When daunomycin and actinomycin D were added to cells previously stimulated with cAMP, phosphodiesterase was still synthesized at a higher rate than in cells not pretreated with cAMP. These results suggest that cAMP acts at two sites at least, i.e., on enzyme synthesis at the transcription level, and in suppressing the degradation of phosphodiesterase."}
{"id": "PMID:227847", "title": "Hormonal effects on the biosynthesis of lactate dehydrogenase in rat hepatocytes.", "content": "Rat hepatocytes have been studied in suspension culture for 10-h periods. Levels of extractable lactate dehydrogenase (LDH) have been measured in these hepatocytes at hourly intervals in order to note the balance between biosynthesis and degradation of this enzyme. Newly synthesized LDH has been measured by following the rate of incorporation of [3H]leucine into radiochemically pure LDH of high specific catalytic activity as isolated by a rapid affinity chromatographic procedure. The effects of the addition of physiological concentrations of the following hormones at the beginning of 10-h culture periods immediately following preparation of the hepatocytes by the collagen perfusion procedure have been recorded. The hormones triiodothyronine (T3), insulin, glucagon, and  dexamethasone have been added singly or in combination. The culture medium has supplied variable amounts of these hormones in the 10% of fetal calf (or other) serum added, and the hepatocytes themselves have provided intracellular amounts of hormones. In addition to the added hormones, N6,O2'-dibutyryl cyclic AMP (Bt2cAMP) has also been studied. Control suspensions of hepatocytes show reproducible initial levels of extractable LDH which are maintained or slightly increased during 10 h. Such control systems also incorporate [3H]leucine into total protein and into highly purified LDH at reproducible rates during 10 h of incubation. The effects of added hormones on LDH lavels are as follows: (a) T3 causes about a 2-fold increase in LDH at 7 to 8 h in hepatocytes from young adult animals, an effect which is lowered in either younger or older animals or in thyroidectomized animals. (b) Insulin leads to a similar increase in LDH at 5 to 6 h and a falling off at 8 to 10 h. (c) Glucagon also causes an approximate doubling of the amount of extractable LDH during a 10-doubling of the amount of extractable LDH during a 10-h period. (d) Dexamethasone does not produce an increase. (e) Bt2-cAMP produces an effect indistinguishable from that of glucagon. Paired combinations of these hormones fail to produce an additive response in any case. The combinations of T3 plus dexamethaseon and insulin plus dexamethasone lead to significant reductions in levels of extractable LDH when compared to the single hormone effects cited above. With respect to rates of synthesis of total protein as measured by [3H]leucine incorporation, only glucagon, glucagon plus Bt2-cAMP, glucagon plus insulin, T3 plus Bt2cAMP, and T3 plus insulin produce significant increases during a 10-h period. However, when [3H]leucine incorporation into highly purified LDH is measured as an index of LDH biosynthesis, T3, insulin, and glucagon consistently increase the biosynthetic rates during a 10-h period. Bt2cAMP produces a smaller increase. Dexamethasone fails to produce any significant change when compared to controls. Paired combinations of hormones again do not produce any additive effect on LDH biosynthesis when the hormone producing the higher level is taken as the reference...", "contents": "Hormonal effects on the biosynthesis of lactate dehydrogenase in rat hepatocytes. Rat hepatocytes have been studied in suspension culture for 10-h periods. Levels of extractable lactate dehydrogenase (LDH) have been measured in these hepatocytes at hourly intervals in order to note the balance between biosynthesis and degradation of this enzyme. Newly synthesized LDH has been measured by following the rate of incorporation of [3H]leucine into radiochemically pure LDH of high specific catalytic activity as isolated by a rapid affinity chromatographic procedure. The effects of the addition of physiological concentrations of the following hormones at the beginning of 10-h culture periods immediately following preparation of the hepatocytes by the collagen perfusion procedure have been recorded. The hormones triiodothyronine (T3), insulin, glucagon, and  dexamethasone have been added singly or in combination. The culture medium has supplied variable amounts of these hormones in the 10% of fetal calf (or other) serum added, and the hepatocytes themselves have provided intracellular amounts of hormones. In addition to the added hormones, N6,O2'-dibutyryl cyclic AMP (Bt2cAMP) has also been studied. Control suspensions of hepatocytes show reproducible initial levels of extractable LDH which are maintained or slightly increased during 10 h. Such control systems also incorporate [3H]leucine into total protein and into highly purified LDH at reproducible rates during 10 h of incubation. The effects of added hormones on LDH lavels are as follows: (a) T3 causes about a 2-fold increase in LDH at 7 to 8 h in hepatocytes from young adult animals, an effect which is lowered in either younger or older animals or in thyroidectomized animals. (b) Insulin leads to a similar increase in LDH at 5 to 6 h and a falling off at 8 to 10 h. (c) Glucagon also causes an approximate doubling of the amount of extractable LDH during a 10-doubling of the amount of extractable LDH during a 10-h period. (d) Dexamethasone does not produce an increase. (e) Bt2-cAMP produces an effect indistinguishable from that of glucagon. Paired combinations of these hormones fail to produce an additive response in any case. The combinations of T3 plus dexamethaseon and insulin plus dexamethasone lead to significant reductions in levels of extractable LDH when compared to the single hormone effects cited above. With respect to rates of synthesis of total protein as measured by [3H]leucine incorporation, only glucagon, glucagon plus Bt2-cAMP, glucagon plus insulin, T3 plus Bt2cAMP, and T3 plus insulin produce significant increases during a 10-h period. However, when [3H]leucine incorporation into highly purified LDH is measured as an index of LDH biosynthesis, T3, insulin, and glucagon consistently increase the biosynthetic rates during a 10-h period. Bt2cAMP produces a smaller increase. Dexamethasone fails to produce any significant change when compared to controls. Paired combinations of hormones again do not produce any additive effect on LDH biosynthesis when the hormone producing the higher level is taken as the reference..."}
{"id": "PMID:227848", "title": "Kinetic and mechanistic studies on the reduction of melilotate hydroxylase by reduced pyridine nucleotides.", "content": "The reduction of the melilotate hydroxylase . 2-OH-phenyl propionate complex by NADH and reduced 3-acetyl pyridine adenine dinucleotide (AcPyNADH) has been investigated using steady state kinetic and rapid reaction techniques. Reduction by NADH appeared to involve only one charge-transfer-type intermediate (between reduced enzyme and NAD) as previously described (Strickland, S., and Massey, V. (1973) J. Biol. Chem. 248, 2953-2962). Reduction by AcPyNADH was shown to involve two charge-transfer-type intermediates. The first was between oxidized enzyme and AcPyNADH and the second was between reduced enzyme and AcPyNAD. Reaction of AcPyNADH with oxidized enzyme . 2-OH-phenyl propionate complex to form the first charge-transfer complex reached equilibrium within the mixing time of the stopped flow apparatus (5 ms). Subsequent steps in the reaction appeared to be first order and were independent of the AcPyNADH concentration. An 8-fold deuterium isotope effect on the step involving flavin reduction was found when reduced 3-acetyl[4A-2H]pyridine adenine dinucleotide (AcPyNADD) was used as the reductant. Analysis of the rapid reaction results for the reaction of oxidized pyridine nucleotide with reduced enzyme . 2-OH-phenyl propionate complex indicated the presence of two forms of reduced enzyme (in equilibrium) of which only one form was capable of reacting with the oxidized pyridine nucleotide. Based on the rapid reaction data, a mechanism for the reduction half-reaction is proposed. The turnover number calculated from this mechanism is in good agreement with that determined from the steady state data.", "contents": "Kinetic and mechanistic studies on the reduction of melilotate hydroxylase by reduced pyridine nucleotides. The reduction of the melilotate hydroxylase . 2-OH-phenyl propionate complex by NADH and reduced 3-acetyl pyridine adenine dinucleotide (AcPyNADH) has been investigated using steady state kinetic and rapid reaction techniques. Reduction by NADH appeared to involve only one charge-transfer-type intermediate (between reduced enzyme and NAD) as previously described (Strickland, S., and Massey, V. (1973) J. Biol. Chem. 248, 2953-2962). Reduction by AcPyNADH was shown to involve two charge-transfer-type intermediates. The first was between oxidized enzyme and AcPyNADH and the second was between reduced enzyme and AcPyNAD. Reaction of AcPyNADH with oxidized enzyme . 2-OH-phenyl propionate complex to form the first charge-transfer complex reached equilibrium within the mixing time of the stopped flow apparatus (5 ms). Subsequent steps in the reaction appeared to be first order and were independent of the AcPyNADH concentration. An 8-fold deuterium isotope effect on the step involving flavin reduction was found when reduced 3-acetyl[4A-2H]pyridine adenine dinucleotide (AcPyNADD) was used as the reductant. Analysis of the rapid reaction results for the reaction of oxidized pyridine nucleotide with reduced enzyme . 2-OH-phenyl propionate complex indicated the presence of two forms of reduced enzyme (in equilibrium) of which only one form was capable of reacting with the oxidized pyridine nucleotide. Based on the rapid reaction data, a mechanism for the reduction half-reaction is proposed. The turnover number calculated from this mechanism is in good agreement with that determined from the steady state data."}
{"id": "PMID:227849", "title": "Isolation of the domain containing the molybdenum, iron-sulfur I, and iron-sulfur II centers of chicken liver xanthine dehydrogenase.", "content": "Chicken liver xanthine dehydrogenase, like other xanthine-oxidizing enzymes, is a dimer of Mr = 150,000 subunits. Each subunit contains one molybdenum, one FAD, and two distinct Fe2S2 centers. Treatment with a number of proteases shows that the native enzyme subunit is cleaved at three distinct sites. However, the cleavage products can be separated only under denaturing conditions. Prolonged treatment with subtilisin at pH 10.1 has permitted the isolation of an Mr = 65,000 catalytically active fragment that is devoid of FAD but which contains the molybdenum and both types of iron-sulfur center. A model of the domain structure of the native enzyme is proposed.", "contents": "Isolation of the domain containing the molybdenum, iron-sulfur I, and iron-sulfur II centers of chicken liver xanthine dehydrogenase. Chicken liver xanthine dehydrogenase, like other xanthine-oxidizing enzymes, is a dimer of Mr = 150,000 subunits. Each subunit contains one molybdenum, one FAD, and two distinct Fe2S2 centers. Treatment with a number of proteases shows that the native enzyme subunit is cleaved at three distinct sites. However, the cleavage products can be separated only under denaturing conditions. Prolonged treatment with subtilisin at pH 10.1 has permitted the isolation of an Mr = 65,000 catalytically active fragment that is devoid of FAD but which contains the molybdenum and both types of iron-sulfur center. A model of the domain structure of the native enzyme is proposed."}
{"id": "PMID:227855", "title": "Paraquat and Escherichia coli. Mechanism of production of extracellular superoxide radical.", "content": "Paraquat mediates a superoxide dismutase-inhibitable reduction of cytochrome c by suspensions of Escherichia coli B. Glucose was most effective in providing electrons for this cytochrome c reduction, but other nutrients could serve in this capacity, provided the cells were preconditioned by growth on these nutrients. Paraquat reduction depended upon a NADPH:paraquat diaphorase, present in the cytosol. Reduced paraquat could diffuse across the cell envelope and react with dioxygen, in the suspending medium, thus generating O2- in that compartment. Most of the paraquat reduced in the cell, under the conditions used, reoxidized in situ and most of the O2- production was thus intracellular. The partitioning of reduced paraquat between intracellular and extracellular compartments, prior to reaction with dioxygen, depended upon intracellular pO2 and any strategy which raised intracellular pO2 decreased the efflux of reduced paraquat and thus decreased extracellular O2- production. Extracellular O2- and H2O2 did contribute to cell damage in proportion to the amount produced. O2- appeared to be unable to cross the cell envelope in either direction and the only O2- which was effective in raising the rate of biosynthesis of the manganese-superoxide dismutase, was that generated within the cell.", "contents": "Paraquat and Escherichia coli. Mechanism of production of extracellular superoxide radical. Paraquat mediates a superoxide dismutase-inhibitable reduction of cytochrome c by suspensions of Escherichia coli B. Glucose was most effective in providing electrons for this cytochrome c reduction, but other nutrients could serve in this capacity, provided the cells were preconditioned by growth on these nutrients. Paraquat reduction depended upon a NADPH:paraquat diaphorase, present in the cytosol. Reduced paraquat could diffuse across the cell envelope and react with dioxygen, in the suspending medium, thus generating O2- in that compartment. Most of the paraquat reduced in the cell, under the conditions used, reoxidized in situ and most of the O2- production was thus intracellular. The partitioning of reduced paraquat between intracellular and extracellular compartments, prior to reaction with dioxygen, depended upon intracellular pO2 and any strategy which raised intracellular pO2 decreased the efflux of reduced paraquat and thus decreased extracellular O2- production. Extracellular O2- and H2O2 did contribute to cell damage in proportion to the amount produced. O2- appeared to be unable to cross the cell envelope in either direction and the only O2- which was effective in raising the rate of biosynthesis of the manganese-superoxide dismutase, was that generated within the cell."}
{"id": "PMID:227860", "title": "Changes in the EPR signal of dinitrogenase from Azotobacter vinelandii during the lag period before hydrogen evolution begins.", "content": "During the lag period before H2 is evolved by the nitrogenase system, the EPR signal of dinitrogenase decreases steadily, indicating transfer of electrons into dinitrogenase. The rate constant for the decrease in amplitude of the EPR signal, the steady state rate of H2 evolution from nitrogenase, and the length of the lag period have been measured. The data suggest that H2 is evolved only after dinitrogenase has been reduced by 2 electrons/molybdenum. The electrons that have been transfered into dinitrogenase during the lag period are not evolved as H2 upon denaturation of dinitrogenase. The existence of a lag indicates that the two nitrogenase proteins dissociate after every electron transfer. The lag occurs and the nitrogenase proteins dissociate under a variety of conditions of pH and temperature.", "contents": "Changes in the EPR signal of dinitrogenase from Azotobacter vinelandii during the lag period before hydrogen evolution begins. During the lag period before H2 is evolved by the nitrogenase system, the EPR signal of dinitrogenase decreases steadily, indicating transfer of electrons into dinitrogenase. The rate constant for the decrease in amplitude of the EPR signal, the steady state rate of H2 evolution from nitrogenase, and the length of the lag period have been measured. The data suggest that H2 is evolved only after dinitrogenase has been reduced by 2 electrons/molybdenum. The electrons that have been transfered into dinitrogenase during the lag period are not evolved as H2 upon denaturation of dinitrogenase. The existence of a lag indicates that the two nitrogenase proteins dissociate after every electron transfer. The lag occurs and the nitrogenase proteins dissociate under a variety of conditions of pH and temperature."}
{"id": "PMID:227861", "title": "Search for a DNA gyrase in mammalian mitochondria.", "content": "Incorporation of labeled deoxynucleoside triphosphates into mtDNA by isolated rat liver mitochondria has been shown previously to reflect DNA replication. We have used this system to seek evidence for a mtDNA gyrase. Coumermycin, novobiocin, nalidixic acid, and oxolinic acid are known to be inhibitors of Escherichia coli gyrase, to inhibit E. coli DNA replication, to abolish colicin E1 replication, and to depress the supercoiling of phage lambda DNA, the last two via inhibition of the DNA gyrase. Our results show that these agents inhibit [3H]dATP incorporation into bulk mtDNA at concentrations similar to those used for E. coli. Analysis by sucrose gradient sedimentation confirms the inhibition and shows further that the synthesis of the highly supercoiled form of mtDNA (i.e. 39 S DNA) is depressed relative to other mtDNA forms (i.e. 27 S DNA), suggesting an inhibition of the supercoiling process. Analysis of the DNA by CsCl/propidium diiodide centrifugation shows, in addition, that incubation with coumermycin results in the appearance of a mtDNA form shown to be relaxed mtDNA. The results are consistent with the occurrence of a mtDNA gyrase and its operation in mtDNA replication.", "contents": "Search for a DNA gyrase in mammalian mitochondria. Incorporation of labeled deoxynucleoside triphosphates into mtDNA by isolated rat liver mitochondria has been shown previously to reflect DNA replication. We have used this system to seek evidence for a mtDNA gyrase. Coumermycin, novobiocin, nalidixic acid, and oxolinic acid are known to be inhibitors of Escherichia coli gyrase, to inhibit E. coli DNA replication, to abolish colicin E1 replication, and to depress the supercoiling of phage lambda DNA, the last two via inhibition of the DNA gyrase. Our results show that these agents inhibit [3H]dATP incorporation into bulk mtDNA at concentrations similar to those used for E. coli. Analysis by sucrose gradient sedimentation confirms the inhibition and shows further that the synthesis of the highly supercoiled form of mtDNA (i.e. 39 S DNA) is depressed relative to other mtDNA forms (i.e. 27 S DNA), suggesting an inhibition of the supercoiling process. Analysis of the DNA by CsCl/propidium diiodide centrifugation shows, in addition, that incubation with coumermycin results in the appearance of a mtDNA form shown to be relaxed mtDNA. The results are consistent with the occurrence of a mtDNA gyrase and its operation in mtDNA replication."}
{"id": "PMID:227864", "title": "The recognition of a special ubiquinone functionally central in the ubiquinone-cytochrome b-c2 oxidoreductase.", "content": "Although the energy conserving membranes of the photosynthetic bacterium Rhodopseudomonas sphaeroides contain a 25 (+/- 3)-fold molar excess of ubiquinone over the photochemical reaction center, the activity of the ubiquinone-cytochrome b-c2 oxidoreductase is unaffected by quinone extraction until only 3, or at most 4, ubiquinones remain; only then does further extraction prevent the function of the oxidoreductase. Since 2 of these last ubiquinones are integral parts of the photochemical reaction center, we conclude that the ubiquinone-cytochrome b-c2 oxidoreductase requires only 1, or at most 2, molecules of ubiquinone-10 for its function. Earlier kinetic data identified a major electron donor to ferricytochrome c2 as a single molecule (known as Z) which requires 2 electrons and 2 protons for its equilibrium reduction. Hence, we identify a single molecule of quinone, probably ubiquinone-10 in a special environment, as a major electron donor to ferricytochrome c2 in the ubiquinone cytochrome b-c2 oxidoreductase.", "contents": "The recognition of a special ubiquinone functionally central in the ubiquinone-cytochrome b-c2 oxidoreductase. Although the energy conserving membranes of the photosynthetic bacterium Rhodopseudomonas sphaeroides contain a 25 (+/- 3)-fold molar excess of ubiquinone over the photochemical reaction center, the activity of the ubiquinone-cytochrome b-c2 oxidoreductase is unaffected by quinone extraction until only 3, or at most 4, ubiquinones remain; only then does further extraction prevent the function of the oxidoreductase. Since 2 of these last ubiquinones are integral parts of the photochemical reaction center, we conclude that the ubiquinone-cytochrome b-c2 oxidoreductase requires only 1, or at most 2, molecules of ubiquinone-10 for its function. Earlier kinetic data identified a major electron donor to ferricytochrome c2 as a single molecule (known as Z) which requires 2 electrons and 2 protons for its equilibrium reduction. Hence, we identify a single molecule of quinone, probably ubiquinone-10 in a special environment, as a major electron donor to ferricytochrome c2 in the ubiquinone cytochrome b-c2 oxidoreductase."}
{"id": "PMID:227869", "title": "Effects of adrenalectomy on hormone action on hepatic glucose metabolism. Impaired glucagon activation of glycogen phosphorylase in hepatocytes from adrenalectomized rats.", "content": "The effects of adrenalectomy on glucagon activation of liver glycogen phosphorylase and glycogenolysis were studied in isolated hepatocytes. Adrenalectomy resulted in reduced responsiveness of glycogenolysis and phosphorylase to glucagon activation. Stimulation of cAMP accumulation and cAMP-dependent protein kinase activity by glucagon was unaltered in cells from adrenalectomized rats. Adrenalectomy did not alter the proportion of type I and type II protein kinase isozymes in liver, whereas this was changed by fasting. Activation of phosphorylase kinase by glucagon was reduced in hepatocytes from adrenalectomized rats, although the half-maximal effective concentration of glucagon was unchanged. No difference in phosphorylase phosphatase activity between liver cells from control and adrenalectomized rats was detected. Glucagon-activated phosphorylase declined rapidly in hepatocytes from adrenalectomized rats, whereas the time course of cAMP increase in response to glucagon was normal. Addition  of glucose (15 mM) rapidly inactivated glucagon-stimulated phosphorylase in both adrenalectomized and control rat hepatocytes. The inactivation by glucose was reversed by increasing glucagon concentration in cells from control rats, but was accelerated in cells from adrenalectomized rats. It is concluded that impaired activation of phosphorylase kinase contributes to the reduced glucagon stimulation of hepatic glycogenolysis in adrenalectomized rats. The possible role of changes in phosphorylase phosphatase is discussed.", "contents": "Effects of adrenalectomy on hormone action on hepatic glucose metabolism. Impaired glucagon activation of glycogen phosphorylase in hepatocytes from adrenalectomized rats. The effects of adrenalectomy on glucagon activation of liver glycogen phosphorylase and glycogenolysis were studied in isolated hepatocytes. Adrenalectomy resulted in reduced responsiveness of glycogenolysis and phosphorylase to glucagon activation. Stimulation of cAMP accumulation and cAMP-dependent protein kinase activity by glucagon was unaltered in cells from adrenalectomized rats. Adrenalectomy did not alter the proportion of type I and type II protein kinase isozymes in liver, whereas this was changed by fasting. Activation of phosphorylase kinase by glucagon was reduced in hepatocytes from adrenalectomized rats, although the half-maximal effective concentration of glucagon was unchanged. No difference in phosphorylase phosphatase activity between liver cells from control and adrenalectomized rats was detected. Glucagon-activated phosphorylase declined rapidly in hepatocytes from adrenalectomized rats, whereas the time course of cAMP increase in response to glucagon was normal. Addition  of glucose (15 mM) rapidly inactivated glucagon-stimulated phosphorylase in both adrenalectomized and control rat hepatocytes. The inactivation by glucose was reversed by increasing glucagon concentration in cells from control rats, but was accelerated in cells from adrenalectomized rats. It is concluded that impaired activation of phosphorylase kinase contributes to the reduced glucagon stimulation of hepatic glycogenolysis in adrenalectomized rats. The possible role of changes in phosphorylase phosphatase is discussed."}
{"id": "PMID:227871", "title": "Metabolism of Okazaki fragments during simian virus 40 DNA replication.", "content": "Essentially all of the Okazaki fragments on replicating Simian virus 40 (SV40)DNA could be grouped into one of three classes. Class I Okazaki fragments (about 20%) were separated from longer nascent DNA chains by a single phosphodiester bond interruption (nick) and were quantitatively identified by treating purified replicating DNA with Escherichia coli DNA ligase and then measuring the fraction of Okazaki fragments joined to longer nascent DNA chains. Similarly, class II Okazaki fragments (about 30%) were separated by a region of single-stranded DNA template (gap) that could be filled and sealed by T4 DNA polymerase plus E. coli DNA ligase, and class III fragments (about 50%) were separated by RNA primers that could be removed with E. coli DNA olymerase I, allowing the fragments to be joined with E. coli DNA ligase. These results were obtained with replicating SV40 DNA that had been briefly labeled with radioactive precursors in either intact cells or isolated nuclei. When isolated nuclei were further incubated in the presence of cytosol, all of the Okazaki fragments were converted into longer DNA strands as expected for intermediates in DNA synthesis. However, when washed nuclei were incubated in the abscence of cytosol, both class I and class II Okazaki fragments accumulated despite the excision of RNA primers: class III Okazaki fragments and RNA-DNA covalent linkages both disappeared at similar rates. These data demonstrate the existence of RNA primers in whole cells as well as in isolated nuclei, and identify a unique gap-filling step that is not simply an extension of the DNA chain elongation process concomitant with the excision of RNA primers. One or more factos found in cytosol, in addition to DNA polymerase alpha, are specifically involved in the gap-filling and ligation steps. The sizes of mature Okazaki fragments (class I) and Okazaki fragments whose synthesis was completed by T4 DNA polymerase were measured by gel electrophoresis and found to be broadly distributed between 40 and 290 nucleotides with an average length of 135 nucleotides. Since 80% and 90% of the Okazaments does not occur at uniformly spaced intervals along the DNA template. During the excision of RNA primers, nascent DNA chains with a single ribonucleotide covalently attached to the 5' terminus were identified as transient intermediates. These intermediates accumulated during excision of RNA primers in the presence of adenine 9-beta-D-arabinoside 5'-triphosphate, and those Okazaki fragments blocked by RNA primers (class III) were found to have originated the farthest from the 5' ends of long nascent DNA strands. Thus, RNA primers appear to be excised in two steps with the second step, removal of the final ribonucleotide, being stimulated by concomitant DNA synthesis. These and other data were used to construct a comprehensive metabolic pathway for the initiation, elongation, and maturation of Okazaki fragments at mammalian DNA replication forks.", "contents": "Metabolism of Okazaki fragments during simian virus 40 DNA replication. Essentially all of the Okazaki fragments on replicating Simian virus 40 (SV40)DNA could be grouped into one of three classes. Class I Okazaki fragments (about 20%) were separated from longer nascent DNA chains by a single phosphodiester bond interruption (nick) and were quantitatively identified by treating purified replicating DNA with Escherichia coli DNA ligase and then measuring the fraction of Okazaki fragments joined to longer nascent DNA chains. Similarly, class II Okazaki fragments (about 30%) were separated by a region of single-stranded DNA template (gap) that could be filled and sealed by T4 DNA polymerase plus E. coli DNA ligase, and class III fragments (about 50%) were separated by RNA primers that could be removed with E. coli DNA olymerase I, allowing the fragments to be joined with E. coli DNA ligase. These results were obtained with replicating SV40 DNA that had been briefly labeled with radioactive precursors in either intact cells or isolated nuclei. When isolated nuclei were further incubated in the presence of cytosol, all of the Okazaki fragments were converted into longer DNA strands as expected for intermediates in DNA synthesis. However, when washed nuclei were incubated in the abscence of cytosol, both class I and class II Okazaki fragments accumulated despite the excision of RNA primers: class III Okazaki fragments and RNA-DNA covalent linkages both disappeared at similar rates. These data demonstrate the existence of RNA primers in whole cells as well as in isolated nuclei, and identify a unique gap-filling step that is not simply an extension of the DNA chain elongation process concomitant with the excision of RNA primers. One or more factos found in cytosol, in addition to DNA polymerase alpha, are specifically involved in the gap-filling and ligation steps. The sizes of mature Okazaki fragments (class I) and Okazaki fragments whose synthesis was completed by T4 DNA polymerase were measured by gel electrophoresis and found to be broadly distributed between 40 and 290 nucleotides with an average length of 135 nucleotides. Since 80% and 90% of the Okazaments does not occur at uniformly spaced intervals along the DNA template. During the excision of RNA primers, nascent DNA chains with a single ribonucleotide covalently attached to the 5' terminus were identified as transient intermediates. These intermediates accumulated during excision of RNA primers in the presence of adenine 9-beta-D-arabinoside 5'-triphosphate, and those Okazaki fragments blocked by RNA primers (class III) were found to have originated the farthest from the 5' ends of long nascent DNA strands. Thus, RNA primers appear to be excised in two steps with the second step, removal of the final ribonucleotide, being stimulated by concomitant DNA synthesis. These and other data were used to construct a comprehensive metabolic pathway for the initiation, elongation, and maturation of Okazaki fragments at mammalian DNA replication forks."}
{"id": "PMID:227873", "title": "Deoxyribonucleic acid polymerase of bacteriophage T7. Characterization of the exonuclease activities of the gene 5 protein and the reconstituted polymerase.", "content": "Homogeneous gene 5 protein of bacteriophage T7, a subunit of T7 DNA polymerase, catalyzes the stepwise hydrolysis of single-stranded DNA in a 3' leads to 5' direction to yield nucleoside 5'-monophosphates. The gene 5 protein itself does not hydrolyze duplex DNA. However, in the presence of Escherichia coli thioredoxin, the host-specified subunit of T7 DNA polymerase, duplex DNA is hydrolyzed in a 3' leads to 5' direction to yield nucleoside 5'-monophosphates. The apparent Km for thioredoxin in the reaction is 4.8 x 10(-8) M, a value similar to that for the apparent Km of thioredoxin in the complementation assay with gene 5 protein to restore T7 DNA polymerase activity. Both exonuclease activities require Mg2+ and a sulfhydryl reagent for optimal activity, and both activities are sensitive to salt concentration. Deoxyribonucleoside 5'-triphosphates inhibit hydrolysis by both exonuclease activities; hydrolysis of single-stranded DNA by the gene 5 protein is inhibited even in the absence of thioredoxin where there is less than 2% active T7 DNA polymerase. E. coli DNA binding protein (helix destabilizing protein) stimulates the hydrolysis of duplex DNA up to 9-fold under conditions where the hydrolysis of the single-stranded DNA is inhibited 4-fold.", "contents": "Deoxyribonucleic acid polymerase of bacteriophage T7. Characterization of the exonuclease activities of the gene 5 protein and the reconstituted polymerase. Homogeneous gene 5 protein of bacteriophage T7, a subunit of T7 DNA polymerase, catalyzes the stepwise hydrolysis of single-stranded DNA in a 3' leads to 5' direction to yield nucleoside 5'-monophosphates. The gene 5 protein itself does not hydrolyze duplex DNA. However, in the presence of Escherichia coli thioredoxin, the host-specified subunit of T7 DNA polymerase, duplex DNA is hydrolyzed in a 3' leads to 5' direction to yield nucleoside 5'-monophosphates. The apparent Km for thioredoxin in the reaction is 4.8 x 10(-8) M, a value similar to that for the apparent Km of thioredoxin in the complementation assay with gene 5 protein to restore T7 DNA polymerase activity. Both exonuclease activities require Mg2+ and a sulfhydryl reagent for optimal activity, and both activities are sensitive to salt concentration. Deoxyribonucleoside 5'-triphosphates inhibit hydrolysis by both exonuclease activities; hydrolysis of single-stranded DNA by the gene 5 protein is inhibited even in the absence of thioredoxin where there is less than 2% active T7 DNA polymerase. E. coli DNA binding protein (helix destabilizing protein) stimulates the hydrolysis of duplex DNA up to 9-fold under conditions where the hydrolysis of the single-stranded DNA is inhibited 4-fold."}
{"id": "PMID:227874", "title": "Reaction of copper-zinc superoxide dismutase with diethyldithiocarbamate.", "content": "Diethyldithiocarbamate reacted with superoxide dismutase from bovine erythrocytes. Changes in both optical and esr spectra, which accompanied this reaction, indicated involvement of the Cu(II). The reaction was accelerated by raising the concentrations of the reactants, elevating the temperature, and lowering the pH, in the range 10.2 to 5.5, and it was independent of the presence of oxygen. During the first phase of this reaction the Cu(II).diethyldithiocarbamate complex remained bound to the enzyme and the catalytic activity did not diminish. There followed a second and slower process which was accompanied by the appearance of colloidal Cu(II).chelate complex and by a loss of activity which could be restored by the addition of CuSO4. All of the observations are accomodated by a model in which 1 diethyldithiocarbamate molecule reacts/copper center, with retention of activity, in Phase I, while a second diethyldithiocarbamate displaces the copper, with a loss of activity, in Phase II.", "contents": "Reaction of copper-zinc superoxide dismutase with diethyldithiocarbamate. Diethyldithiocarbamate reacted with superoxide dismutase from bovine erythrocytes. Changes in both optical and esr spectra, which accompanied this reaction, indicated involvement of the Cu(II). The reaction was accelerated by raising the concentrations of the reactants, elevating the temperature, and lowering the pH, in the range 10.2 to 5.5, and it was independent of the presence of oxygen. During the first phase of this reaction the Cu(II).diethyldithiocarbamate complex remained bound to the enzyme and the catalytic activity did not diminish. There followed a second and slower process which was accompanied by the appearance of colloidal Cu(II).chelate complex and by a loss of activity which could be restored by the addition of CuSO4. All of the observations are accomodated by a model in which 1 diethyldithiocarbamate molecule reacts/copper center, with retention of activity, in Phase I, while a second diethyldithiocarbamate displaces the copper, with a loss of activity, in Phase II."}
{"id": "PMID:227875", "title": "Effect of antimitotic drugs on tubulin GTPase activity and self-assembly.", "content": "Microtubule inhibitors can be classified into two categories: 1) those which inhibit the polymerization-dependent GTPase activity of phosphocellulose-purified tubulin, but induce a significant polymerization-independent GTPase activity (e.g. colchicine, griseofulvine, daunorubicine); 2) those which inhibit the GTPase activity associated with tubulin polymerization and that induced by inhibitors of the first class (e.g. the vincaalkaloids and podophyllotoxin). The colchicine-stimulated GTPase activity of tubulin appears to be due to the tubulin.colchicine complex. This suggests that colchicine inhibits tubulin assembly by binding to a tubulin-tubulin interaction site required for the polymerization-dependent GTPase activity and induces by itself a tubulin conformational change that leads to polymerization-independent GTPase activity. Stoichiometry of inhibition by vinblastine of the colchicine-stimulated GTPase activity is 1:2. On the other hand, the inhibition by vinblastine of the tubulin self-assembly and of the polymerization-dependent GTPase activity is strongly substoichiometric at the beginning of the polymerization reaction, 1 vinblastine molecule inhibiting the ability of 10 tubulin dimers to polymerize and to hydrolyze the GTP. However, at the polymerization plateau, the inhibition effect by vinblastine appears to be lower, suggesting a selective action of vinblastine on the early stages of the polymerization reaction.", "contents": "Effect of antimitotic drugs on tubulin GTPase activity and self-assembly. Microtubule inhibitors can be classified into two categories: 1) those which inhibit the polymerization-dependent GTPase activity of phosphocellulose-purified tubulin, but induce a significant polymerization-independent GTPase activity (e.g. colchicine, griseofulvine, daunorubicine); 2) those which inhibit the GTPase activity associated with tubulin polymerization and that induced by inhibitors of the first class (e.g. the vincaalkaloids and podophyllotoxin). The colchicine-stimulated GTPase activity of tubulin appears to be due to the tubulin.colchicine complex. This suggests that colchicine inhibits tubulin assembly by binding to a tubulin-tubulin interaction site required for the polymerization-dependent GTPase activity and induces by itself a tubulin conformational change that leads to polymerization-independent GTPase activity. Stoichiometry of inhibition by vinblastine of the colchicine-stimulated GTPase activity is 1:2. On the other hand, the inhibition by vinblastine of the tubulin self-assembly and of the polymerization-dependent GTPase activity is strongly substoichiometric at the beginning of the polymerization reaction, 1 vinblastine molecule inhibiting the ability of 10 tubulin dimers to polymerize and to hydrolyze the GTP. However, at the polymerization plateau, the inhibition effect by vinblastine appears to be lower, suggesting a selective action of vinblastine on the early stages of the polymerization reaction."}
{"id": "PMID:227877", "title": "The uncoupled regulation of fibronectin and collagen synthesis in Rous sarcoma virus transformed avian tendon cells.", "content": "We have investigated the regulation of fibronectin and procollagen synthesis in normal and Rous sarcoma virus transformed primary avian tendon cells. These two proteins interact at the cell periphery and both are reportedly lost upon transformation. We thus examined whether their synthesis was coordinately regulated in Rous sarcoma virus-infected cells. It was found that while the synthesis of both pro alpha 1 and pro alpha 2 peptides was reduced upon transformation, the synthesis of fibronectin was not altered. Nevertheless, long term radiolabeling demonstrated that fibronectin levels were reduced in transformed cells. It is concluded that the reduction in levels of these components at the surface is brought about by different mechanisms; collagen levels being regulated by procollagen synthesis and fibronectin levels by degradation and/or release into the culture medium. The possibility is discussed that fibronectin is lost from the cell periphery of primary avian tendon cells as a consequence of decreased levels of anchoring collagen molecules.", "contents": "The uncoupled regulation of fibronectin and collagen synthesis in Rous sarcoma virus transformed avian tendon cells. We have investigated the regulation of fibronectin and procollagen synthesis in normal and Rous sarcoma virus transformed primary avian tendon cells. These two proteins interact at the cell periphery and both are reportedly lost upon transformation. We thus examined whether their synthesis was coordinately regulated in Rous sarcoma virus-infected cells. It was found that while the synthesis of both pro alpha 1 and pro alpha 2 peptides was reduced upon transformation, the synthesis of fibronectin was not altered. Nevertheless, long term radiolabeling demonstrated that fibronectin levels were reduced in transformed cells. It is concluded that the reduction in levels of these components at the surface is brought about by different mechanisms; collagen levels being regulated by procollagen synthesis and fibronectin levels by degradation and/or release into the culture medium. The possibility is discussed that fibronectin is lost from the cell periphery of primary avian tendon cells as a consequence of decreased levels of anchoring collagen molecules."}
{"id": "PMID:227880", "title": "Photoaffinity inactivation of the enkephalin receptor.", "content": "An arylazide enkephalin derivative, [D-Ala2,Met5]enkephalin-Tyr-N-(2-nitro-4-azidophenyl) ethylenediamine (ETN), has been synthesized. In the dark, it inhibited the binding of [3H]enkephalinamide to enkephalin receptor-rich NG-108 cell membranes with an I50 = 2.2 X 10(-8) M or KI = 7 X 10(-9) M, assuming competitive inhibition. Photolysis of membranes in the presence of ETN caused irreversible inactivation of the enkephalin receptor, but inactivation was prevented by the addition of enkephalin, the half-effective concentration being 3 x 10(-9) M. ETN appears to be an effective photoaffinity label for the enkephalin receptor.", "contents": "Photoaffinity inactivation of the enkephalin receptor. An arylazide enkephalin derivative, [D-Ala2,Met5]enkephalin-Tyr-N-(2-nitro-4-azidophenyl) ethylenediamine (ETN), has been synthesized. In the dark, it inhibited the binding of [3H]enkephalinamide to enkephalin receptor-rich NG-108 cell membranes with an I50 = 2.2 X 10(-8) M or KI = 7 X 10(-9) M, assuming competitive inhibition. Photolysis of membranes in the presence of ETN caused irreversible inactivation of the enkephalin receptor, but inactivation was prevented by the addition of enkephalin, the half-effective concentration being 3 x 10(-9) M. ETN appears to be an effective photoaffinity label for the enkephalin receptor."}
{"id": "PMID:227881", "title": "The formation of binary and ternary complexes of cytochrome P-450scc with adrenodoxin and adrenodoxin reductase.adrenodoxin complex. The implication in ACTH function.", "content": "Binary and ternary complexes of bovine adrenocortical mitochondrial cytochrome P-450scc with adrenodoxin and adrenodoxin reductase.adrenodoxin complex are formed in the presence of cholesterol and Emulgen 913. Both cholesterol and Emulgen 913 are required for the binding of cytochrome P-450scc with adrenodoxin. Since phospholipids are able to replace Emulgen 913 in this reaction, in vivo phospholipids of the mitochondrial inner membrane appear to play the function of the detergent. The dissociation constants of the cytochrome.adrenodoxin complex are 0.3 to 0.4 microM at 130 microM dimyristoylphosphatidylcholine and 0.9 microM at 120 microM Emulgen 913, whereas the dissociation constant for the ternary complex of cytochrome P-450scc with adrenodoxin reductase and adrenodoxin is 4.0 microM at 150 microM Emulgen 913. The stoichiometry of binary and ternary complexes reveals the 1:1 and 1:1:1 molar ratios, respectively, judging from chemical analyses after the fractionation of the complexes by gel filtration. Emulgen 913, Tween 20, ethylene glycol, myristoyllysophosphatidylcholine, dimyristoylphosphatidylcholine, and phosphatidylethanolamine show the enhanced activity of cholesterol side chain cleavage reaction with cytochrome P-450scc, adrenodoxin, adrenodoxin reductase, and NADPH. These results, in conjunction with earlier experiments, lead us to the proposal on the structure of the hydroxylase complex in the membrane and to the hypothesis on the regulation of the enzymatic activity by the availability of substrate cholesterol to the cytochrome. Hence, we propose a mobile P-450scc hypothesis for the response of the mitochondrion to adrenocorticotropic hormone stimuli.", "contents": "The formation of binary and ternary complexes of cytochrome P-450scc with adrenodoxin and adrenodoxin reductase.adrenodoxin complex. The implication in ACTH function. Binary and ternary complexes of bovine adrenocortical mitochondrial cytochrome P-450scc with adrenodoxin and adrenodoxin reductase.adrenodoxin complex are formed in the presence of cholesterol and Emulgen 913. Both cholesterol and Emulgen 913 are required for the binding of cytochrome P-450scc with adrenodoxin. Since phospholipids are able to replace Emulgen 913 in this reaction, in vivo phospholipids of the mitochondrial inner membrane appear to play the function of the detergent. The dissociation constants of the cytochrome.adrenodoxin complex are 0.3 to 0.4 microM at 130 microM dimyristoylphosphatidylcholine and 0.9 microM at 120 microM Emulgen 913, whereas the dissociation constant for the ternary complex of cytochrome P-450scc with adrenodoxin reductase and adrenodoxin is 4.0 microM at 150 microM Emulgen 913. The stoichiometry of binary and ternary complexes reveals the 1:1 and 1:1:1 molar ratios, respectively, judging from chemical analyses after the fractionation of the complexes by gel filtration. Emulgen 913, Tween 20, ethylene glycol, myristoyllysophosphatidylcholine, dimyristoylphosphatidylcholine, and phosphatidylethanolamine show the enhanced activity of cholesterol side chain cleavage reaction with cytochrome P-450scc, adrenodoxin, adrenodoxin reductase, and NADPH. These results, in conjunction with earlier experiments, lead us to the proposal on the structure of the hydroxylase complex in the membrane and to the hypothesis on the regulation of the enzymatic activity by the availability of substrate cholesterol to the cytochrome. Hence, we propose a mobile P-450scc hypothesis for the response of the mitochondrion to adrenocorticotropic hormone stimuli."}
{"id": "PMID:227883", "title": "Biosynthesis and characterization of adrenocorticotropic hormone, alpha-melanocyte-stimulating hormone, and an NH2-terminal fragment of the adrenocorticotropic hormone/beta-lipotropin precursor from rat pars intermedia.", "content": "Isolated intermediate lobe cells from 40 rat pituitaries were incubated for 3 h with [35S]methionine + [3H]-phenylalanine, [35S]methionine, [3H]valine, and [3H]leucine. The cell extracts were purified by carboxymethyl-cellulose chromatography (CMC) and the fraction eluting with ovine adrenocorticotropic hormone (ACTH) was further purified either by another CMC under the same conditions or by high performance liquid chromatography (HPLC). Microsequencing of the product from the second CMC allowed the identification of a peptide containing methionine 4 and phenylalanine 7, as expected for the NH2 terminus of ACTH. Purification by HPLC of a similar peptide obtained from the three other incubations gave three main raoactive peaks which were further characterized by their migration rates on polyacrylamide gels, molecular weight, and microsequencing. Results indicated that intact ACTH (residues 1-39) is present in extracts of rat intermediate lobe, but in very small quantities (less than 1% of the beta-endorphin content). ACTH is probably broken down into smaller fragments, e.g. alpha-melanocyte-stimulating hormone (alpha-MSH) (ACTH, 1-13) and corticotropin-like intermediate lobe peptide (CLIP) (ACTH, 18-39). These studies also revealed with existence of a peptide having identical sequence with the (N-1) terminus of the ACTH/lipotropin (LPH) precursor.", "contents": "Biosynthesis and characterization of adrenocorticotropic hormone, alpha-melanocyte-stimulating hormone, and an NH2-terminal fragment of the adrenocorticotropic hormone/beta-lipotropin precursor from rat pars intermedia. Isolated intermediate lobe cells from 40 rat pituitaries were incubated for 3 h with [35S]methionine + [3H]-phenylalanine, [35S]methionine, [3H]valine, and [3H]leucine. The cell extracts were purified by carboxymethyl-cellulose chromatography (CMC) and the fraction eluting with ovine adrenocorticotropic hormone (ACTH) was further purified either by another CMC under the same conditions or by high performance liquid chromatography (HPLC). Microsequencing of the product from the second CMC allowed the identification of a peptide containing methionine 4 and phenylalanine 7, as expected for the NH2 terminus of ACTH. Purification by HPLC of a similar peptide obtained from the three other incubations gave three main raoactive peaks which were further characterized by their migration rates on polyacrylamide gels, molecular weight, and microsequencing. Results indicated that intact ACTH (residues 1-39) is present in extracts of rat intermediate lobe, but in very small quantities (less than 1% of the beta-endorphin content). ACTH is probably broken down into smaller fragments, e.g. alpha-melanocyte-stimulating hormone (alpha-MSH) (ACTH, 1-13) and corticotropin-like intermediate lobe peptide (CLIP) (ACTH, 18-39). These studies also revealed with existence of a peptide having identical sequence with the (N-1) terminus of the ACTH/lipotropin (LPH) precursor."}
{"id": "PMID:227886", "title": "Enzyme-catalyzed DNA unwinding. A DNA-dependent ATPase from E. coli.", "content": "We have isolated a new DNA-dependent ATPase from E. coli. The enzyme has been purified to greater than 90% purity. It appears to be composed of two identical polypeptide chains of molecular weight 20,000. The enzyme catalyzed the hydrolysis of ATP in the presence, but not in the absence, of single-stranded DNA. Double-stranded DNA is not a cofactor. The products of hydrolysis are ADP and Pi. The enzyme also catalyzed strand separation of duplex DNA in the presence of ATP and E. coli DNA binding protein. Two E. coli proteins capable of promoting strand separation have been reported previously and have been termed helicase I and II (Abdel-Monem, M., and Hoffmann-Berling, H. (1977) Eur. J. Biochem. 79, 33-38). Accordingly, this protein is named helicase III.", "contents": "Enzyme-catalyzed DNA unwinding. A DNA-dependent ATPase from E. coli. We have isolated a new DNA-dependent ATPase from E. coli. The enzyme has been purified to greater than 90% purity. It appears to be composed of two identical polypeptide chains of molecular weight 20,000. The enzyme catalyzed the hydrolysis of ATP in the presence, but not in the absence, of single-stranded DNA. Double-stranded DNA is not a cofactor. The products of hydrolysis are ADP and Pi. The enzyme also catalyzed strand separation of duplex DNA in the presence of ATP and E. coli DNA binding protein. Two E. coli proteins capable of promoting strand separation have been reported previously and have been termed helicase I and II (Abdel-Monem, M., and Hoffmann-Berling, H. (1977) Eur. J. Biochem. 79, 33-38). Accordingly, this protein is named helicase III."}
{"id": "PMID:227888", "title": "Spectroscopic techniques for study of phosphodiester bond formation by Escherichia coli RNA polymerase.", "content": "Nucleotides containing the fluorophore 1-aminonaphthalene-5-sulfonate attached to the gamma phosphoryl group via a phosphoamidate bond are excellent substrates for Escherichia coli DNA-dependent RNA polymerase. Cleavage of the alpha-beta-phosphoryl bond produces significant changes in both absorption and fluorescence spectra. These alterations provide a sensitive and precise means for continuous monitoring of transcription. Under appropriate conditions one can detect the utilization of less than 1 nmol of nucleotide. Since the spectroscopic techniques measure nucleotide utilization they can be used in conjunction with measurements of incorporation of radiolabeled precursor such as [3H]UTP into acid-insoluble material to determine whether significant amounts of acid-soluble oligonucleotides are formed.", "contents": "Spectroscopic techniques for study of phosphodiester bond formation by Escherichia coli RNA polymerase. Nucleotides containing the fluorophore 1-aminonaphthalene-5-sulfonate attached to the gamma phosphoryl group via a phosphoamidate bond are excellent substrates for Escherichia coli DNA-dependent RNA polymerase. Cleavage of the alpha-beta-phosphoryl bond produces significant changes in both absorption and fluorescence spectra. These alterations provide a sensitive and precise means for continuous monitoring of transcription. Under appropriate conditions one can detect the utilization of less than 1 nmol of nucleotide. Since the spectroscopic techniques measure nucleotide utilization they can be used in conjunction with measurements of incorporation of radiolabeled precursor such as [3H]UTP into acid-insoluble material to determine whether significant amounts of acid-soluble oligonucleotides are formed."}
{"id": "PMID:227889", "title": "Further characterization of a depurinated DNA-purine base insertion activity from cultured human fibroblasts.", "content": "The purification from cultured human fibroblasts of a protein that binds specifically to partially depurinated DNA and inserts purines into those sites is described. The purine insertion, but not the binding, requires K+. The DNA binding can be saturated with increasing apurinic sites and is weakened by the presence of adenine or guanine. Base insertion into depurinated DNA is specific for adenine or guanine; none is observed with dATP or dGTP. When the depurinated DNA substrate is specifically cleaved with apurinic endonuclease, no purine insertion occurs. Guanine insertion does not occur into tRNA or depyrimidinated DNA, and thymine is not inserted into either depyrimidinated DNA or depurinated DNA. Purine insertion activity follows Michaelis-Menten kinetics with respect to purintes; the apparent Km values for both adenine and guanine are 5 microM. The enzyme binds the purine bases very tightly. Adenine binding saturates at less than 1 microM adenine, perhaps reflecting the low intracellular adenine concentration. The binding protein specific for UV-irradiated DNA (Feldberg, R.S., and Grossman, L. (1976) Biochemistry 15, 2402-2408) had no detectable purine or pyrimidine base insertion activity with depurinated or depyrimidinated DNAs.", "contents": "Further characterization of a depurinated DNA-purine base insertion activity from cultured human fibroblasts. The purification from cultured human fibroblasts of a protein that binds specifically to partially depurinated DNA and inserts purines into those sites is described. The purine insertion, but not the binding, requires K+. The DNA binding can be saturated with increasing apurinic sites and is weakened by the presence of adenine or guanine. Base insertion into depurinated DNA is specific for adenine or guanine; none is observed with dATP or dGTP. When the depurinated DNA substrate is specifically cleaved with apurinic endonuclease, no purine insertion occurs. Guanine insertion does not occur into tRNA or depyrimidinated DNA, and thymine is not inserted into either depyrimidinated DNA or depurinated DNA. Purine insertion activity follows Michaelis-Menten kinetics with respect to purintes; the apparent Km values for both adenine and guanine are 5 microM. The enzyme binds the purine bases very tightly. Adenine binding saturates at less than 1 microM adenine, perhaps reflecting the low intracellular adenine concentration. The binding protein specific for UV-irradiated DNA (Feldberg, R.S., and Grossman, L. (1976) Biochemistry 15, 2402-2408) had no detectable purine or pyrimidine base insertion activity with depurinated or depyrimidinated DNAs."}
{"id": "PMID:227892", "title": "Synthesis of chromophoric, spin label enzyme substrates useful for cryoenzymology.", "content": "The spin label nitroxide derivative 3-(2,2,5,5-tetramethylpyrroline-1-oxyl)-propen-2-oic acid has been synthesized and characterized by chemical methods. It is a useful intermediate in the preparation of a new class of chromophoric spin label substrates for enzyme studies, as shown by the synthesis of O-3-(2,2,5,5-tetramethylpyrroline-1-oxyl)-propen-2-oyl-L-beta-phenyllactic acid, a specific ester substrate of bovine pancreatic carboxypeptidase A (peptidyl-L-amino acid hydrolase; EC 3.4.12.2). Kinetic parameters of the esterolytic reaction are conveniently determined by UV spectrophotometric methods, and a reaction intermediate can be stabilized in fluid cryosolvent mixtures at subzero temperatures. Results are presented of preliminary electron spin resonance studies to demonstrate that structural relationships of the spin label substrate in a catalytically active configuration to active site residues can be determined for this low temperature-stabilized reaction intermediate. This substrate thus demonstrates the utility of this new class of spin label derivatives for characterization of enzyme reaction intermediates stabilized by cryoenzymologic techniques.", "contents": "Synthesis of chromophoric, spin label enzyme substrates useful for cryoenzymology. The spin label nitroxide derivative 3-(2,2,5,5-tetramethylpyrroline-1-oxyl)-propen-2-oic acid has been synthesized and characterized by chemical methods. It is a useful intermediate in the preparation of a new class of chromophoric spin label substrates for enzyme studies, as shown by the synthesis of O-3-(2,2,5,5-tetramethylpyrroline-1-oxyl)-propen-2-oyl-L-beta-phenyllactic acid, a specific ester substrate of bovine pancreatic carboxypeptidase A (peptidyl-L-amino acid hydrolase; EC 3.4.12.2). Kinetic parameters of the esterolytic reaction are conveniently determined by UV spectrophotometric methods, and a reaction intermediate can be stabilized in fluid cryosolvent mixtures at subzero temperatures. Results are presented of preliminary electron spin resonance studies to demonstrate that structural relationships of the spin label substrate in a catalytically active configuration to active site residues can be determined for this low temperature-stabilized reaction intermediate. This substrate thus demonstrates the utility of this new class of spin label derivatives for characterization of enzyme reaction intermediates stabilized by cryoenzymologic techniques."}
{"id": "PMID:227893", "title": "Studies of the electron-nuclear coupling between Fe(III) and 14N in cytochrome P-450 and in a series of low spin heme compounds.", "content": "We have observed the nuclear modulation pattern in the envelope of electron spin echoes for various low spin paramagnetic heme proteins including cytochrome c, myoglobin hydroxide, myoglobin mercaptoethanol, and cytochrome P-450, using the three-pulse-stimulated echo method. We have also carried out similar experiments with model compounds containing either [14N]- or [15N]imidazole. In many of the compounds studied, we have been able to identify the nuclear modulation effects arising from 14N of the porphyrin ring and have been able to characterize and interpret the modulation effects due to 14N of various nitrogenous axial ligands. We have found that the heme of low spin ferric cytochrome P-450 is coordinated to a nitrogenous ligand, probably imidazole. We have also demonstrated that the remote 14N of the imidazole ligand in a [14N]imidazole-heme-NO-model compound is coupled differently than in myoglobin nitroxide, demonstrating the direct effect of the protein of metal ligand bonding.", "contents": "Studies of the electron-nuclear coupling between Fe(III) and 14N in cytochrome P-450 and in a series of low spin heme compounds. We have observed the nuclear modulation pattern in the envelope of electron spin echoes for various low spin paramagnetic heme proteins including cytochrome c, myoglobin hydroxide, myoglobin mercaptoethanol, and cytochrome P-450, using the three-pulse-stimulated echo method. We have also carried out similar experiments with model compounds containing either [14N]- or [15N]imidazole. In many of the compounds studied, we have been able to identify the nuclear modulation effects arising from 14N of the porphyrin ring and have been able to characterize and interpret the modulation effects due to 14N of various nitrogenous axial ligands. We have found that the heme of low spin ferric cytochrome P-450 is coordinated to a nitrogenous ligand, probably imidazole. We have also demonstrated that the remote 14N of the imidazole ligand in a [14N]imidazole-heme-NO-model compound is coupled differently than in myoglobin nitroxide, demonstrating the direct effect of the protein of metal ligand bonding."}
{"id": "PMID:227897", "title": "Characterization and comparison of membrane-associated and cytosolic cAMP-dependent protein kinases. Studies on human erythrocyte protein kinases.", "content": "Cyclic AMP-dependent protein kinase from human erythrocyte plasma membranes was solubilized with Triton X-100, partially purified, and systematically characterized by a series of physicochemical studies. Sedimentation and gel filtration experiments showed that the 6.6 S holoenzyme had a Stokes radius (a) of 5.7 nm and was dissociated into native 4.8 S cAMP-binding (a = 4.5 nm) and 3.2 S catalytic (a = 2.6 nm) subunits. A minimum subunit molecular weight of 48,000 was established for the regulatory subunit by photoaffinity labeling with 8-azido[32P]cAMP, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and autoradiography. These data suggest an asymmetric tetrameric (R2C2) structure (Mr approximately equal to 160,000) for the membrane-derived enzyme. Membrane-derived protein kinase was characterized as a type I enzyme on the basis of its R subunit molecular weight, pI values (R, 4.9; holoenzyme, 5.75 and 5.95), dissociation by 0.5 M NaCl and 50 microgram/ml of protamine, 20-fold reduced affinity for cAMP in the presence of 0.3 mM MgATP, elution from DEAE-cellulose at low ionic strength, and kinetic and cAMP-binding properties. The physicochemical properties of the membrane protein kinase closely parallel the characteristics of erythrocyte cytosolic protein kinase I but are clearly dissimilar from those of the soluble type II enzyme. Moreover, regulatory subunits of the membrane-associated and cytosolic type I kinases were indistinguishable in size, shape, subunit molecular weight, charge, binding and reassociation properties, and peptide maps of the photoaffinity-labeled cAMP-binding site, suggesting a high degree of structural and functional homology in this pair of enzymes. In view of the predominant occurrence of particulate type II protein kinases in rabbit heart and bovine cerebral cortex, the present results suggest that the distribution of membrane-associated protein kinases may be tissue- or species-specific, but not isoenzyme-specific.", "contents": "Characterization and comparison of membrane-associated and cytosolic cAMP-dependent protein kinases. Studies on human erythrocyte protein kinases. Cyclic AMP-dependent protein kinase from human erythrocyte plasma membranes was solubilized with Triton X-100, partially purified, and systematically characterized by a series of physicochemical studies. Sedimentation and gel filtration experiments showed that the 6.6 S holoenzyme had a Stokes radius (a) of 5.7 nm and was dissociated into native 4.8 S cAMP-binding (a = 4.5 nm) and 3.2 S catalytic (a = 2.6 nm) subunits. A minimum subunit molecular weight of 48,000 was established for the regulatory subunit by photoaffinity labeling with 8-azido[32P]cAMP, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and autoradiography. These data suggest an asymmetric tetrameric (R2C2) structure (Mr approximately equal to 160,000) for the membrane-derived enzyme. Membrane-derived protein kinase was characterized as a type I enzyme on the basis of its R subunit molecular weight, pI values (R, 4.9; holoenzyme, 5.75 and 5.95), dissociation by 0.5 M NaCl and 50 microgram/ml of protamine, 20-fold reduced affinity for cAMP in the presence of 0.3 mM MgATP, elution from DEAE-cellulose at low ionic strength, and kinetic and cAMP-binding properties. The physicochemical properties of the membrane protein kinase closely parallel the characteristics of erythrocyte cytosolic protein kinase I but are clearly dissimilar from those of the soluble type II enzyme. Moreover, regulatory subunits of the membrane-associated and cytosolic type I kinases were indistinguishable in size, shape, subunit molecular weight, charge, binding and reassociation properties, and peptide maps of the photoaffinity-labeled cAMP-binding site, suggesting a high degree of structural and functional homology in this pair of enzymes. In view of the predominant occurrence of particulate type II protein kinases in rabbit heart and bovine cerebral cortex, the present results suggest that the distribution of membrane-associated protein kinases may be tissue- or species-specific, but not isoenzyme-specific."}
{"id": "PMID:227899", "title": "Influence of adrenocorticotropin on transport of a cholesteryl linoleate-low density lipoprotein complex into adrenal tumor cells.", "content": "The action of adrenocorticotropin (ACTH) on the specific (receptor-mediated) uptake of cholesteryl linoleate . low density lipoprotein complexes was examined in Y-1 mouse adrenal tumor cells. High affinity binding (KA 4.1 X 10(8) M) was observed with ACTH; lower affinity was seen in the absence of ACTH. The effect of ACTH was observed within 10 min at physiological concentrations of low density lipoprotein (100 microgram/ml). Binding was followed by uptake (internalization) of the ester . lipoprotein complex which was transported to lysosomes. The site of action of ACTH was localized to the uptake process (internalization) since no effect of ACTH was observed on binding to the cell membrane nor on movement of internalized complex to lysosomes. ACTH increases the transport of cholesterol derived from cholesterol ester to the mitochondria. This cholesterol is converted to 20 alpha-hydroxypregn-4-en-3-one and this conversion is accelerated by ACTH. Dibutyryl cyclic AMP (but not butyrate) also stimulates uptake of cholesteryl linoleate . low density lipoprotein. The process stimulated by ACTH and dibutyryl cyclic AMP is specific for low density (as opposed to high density) lipoprotein and for ACTH as distinct from other peptide hormones. The possible physiological importance of this response is considered.", "contents": "Influence of adrenocorticotropin on transport of a cholesteryl linoleate-low density lipoprotein complex into adrenal tumor cells. The action of adrenocorticotropin (ACTH) on the specific (receptor-mediated) uptake of cholesteryl linoleate . low density lipoprotein complexes was examined in Y-1 mouse adrenal tumor cells. High affinity binding (KA 4.1 X 10(8) M) was observed with ACTH; lower affinity was seen in the absence of ACTH. The effect of ACTH was observed within 10 min at physiological concentrations of low density lipoprotein (100 microgram/ml). Binding was followed by uptake (internalization) of the ester . lipoprotein complex which was transported to lysosomes. The site of action of ACTH was localized to the uptake process (internalization) since no effect of ACTH was observed on binding to the cell membrane nor on movement of internalized complex to lysosomes. ACTH increases the transport of cholesterol derived from cholesterol ester to the mitochondria. This cholesterol is converted to 20 alpha-hydroxypregn-4-en-3-one and this conversion is accelerated by ACTH. Dibutyryl cyclic AMP (but not butyrate) also stimulates uptake of cholesteryl linoleate . low density lipoprotein. The process stimulated by ACTH and dibutyryl cyclic AMP is specific for low density (as opposed to high density) lipoprotein and for ACTH as distinct from other peptide hormones. The possible physiological importance of this response is considered."}
{"id": "PMID:227900", "title": "Electrostatic effects on the kinetics of oxidation-reduction reactions of c-type cytochromes.", "content": "The kinetics of the oxidation-reduction reactions between horse heart cytochrome c, Euglena gracilis cytochrome c552, and ions (ascorbate, ferricyanide, and ferrocyanide) was investigated as a function of ionic strength at pH 7, 25 degrees C. The ionic strength was varied between 0.002 and 0.02 M. Data were analyzed according to four different functions of ionic strength. Results showed that the Kirkwood-Tanford smeared charge model holds well for the calculation of the activity coefficients and that the whole charges of these proteins are reflected in the rates of their reactions. Chemical modifications or changes in the pH that altered the charge of the proteins affected the primary salt effects as predicted by the smeared charge model.", "contents": "Electrostatic effects on the kinetics of oxidation-reduction reactions of c-type cytochromes. The kinetics of the oxidation-reduction reactions between horse heart cytochrome c, Euglena gracilis cytochrome c552, and ions (ascorbate, ferricyanide, and ferrocyanide) was investigated as a function of ionic strength at pH 7, 25 degrees C. The ionic strength was varied between 0.002 and 0.02 M. Data were analyzed according to four different functions of ionic strength. Results showed that the Kirkwood-Tanford smeared charge model holds well for the calculation of the activity coefficients and that the whole charges of these proteins are reflected in the rates of their reactions. Chemical modifications or changes in the pH that altered the charge of the proteins affected the primary salt effects as predicted by the smeared charge model."}
{"id": "PMID:227901", "title": "A slowly dissociating form of the cell surface cyclic adenosine 3':5'-monophosphate receptor of Dictyostelium discoideum.", "content": "Experiments using a phosphodiesterase-minus mutant of Dictyostelium discoideum indicate that ligand-induced loss of cell surface cyclic adenosine 3':5'-monophosphate binding sites (down regulation) can be evoked with concentrations of cyclic adenosine 3':5'-monophosphate as low as 10(-8) M. The loss of receptor sites is observed after 5 min of cell preincubation with cyclic adenosine 3':5'-monophosphate and can be as extensive as 75 to 80%. This decrease in binding sites is correlated with the appearance of a slowly dissociating cyclic adenosine 3':5'-monophosphate binding component. Radioactive cyclic adenosine 3':5'-monophosphate bound to this form of receptor cannot be competed for by nonradioactive cyclic adenosine 3':5'-monophosphate or adenosine 5'-monophosphate and is not accessible to hydrolysis by cyclic adenosine 3':5'-monophosphate phosphodiesterase. The extent of appearance of this binding component is dependent upon the concentration of cyclic adenosine 3':5'-monophosphate used to elicit the down regulation response and the temperature of the incubation medium.", "contents": "A slowly dissociating form of the cell surface cyclic adenosine 3':5'-monophosphate receptor of Dictyostelium discoideum. Experiments using a phosphodiesterase-minus mutant of Dictyostelium discoideum indicate that ligand-induced loss of cell surface cyclic adenosine 3':5'-monophosphate binding sites (down regulation) can be evoked with concentrations of cyclic adenosine 3':5'-monophosphate as low as 10(-8) M. The loss of receptor sites is observed after 5 min of cell preincubation with cyclic adenosine 3':5'-monophosphate and can be as extensive as 75 to 80%. This decrease in binding sites is correlated with the appearance of a slowly dissociating cyclic adenosine 3':5'-monophosphate binding component. Radioactive cyclic adenosine 3':5'-monophosphate bound to this form of receptor cannot be competed for by nonradioactive cyclic adenosine 3':5'-monophosphate or adenosine 5'-monophosphate and is not accessible to hydrolysis by cyclic adenosine 3':5'-monophosphate phosphodiesterase. The extent of appearance of this binding component is dependent upon the concentration of cyclic adenosine 3':5'-monophosphate used to elicit the down regulation response and the temperature of the incubation medium."}
{"id": "PMID:227902", "title": "Very low density lipoprotein. Removal of Apolipoproteins C-II and C-III-1 during lipolysis in vitro.", "content": "In this study we have investigated the effects of very low density lipoprotein (VLDL) lipolysis on the removal of radiolabeled apolipoprotein C-II and apolipoprotein C-III-1 from in vitro lipolyzed lipoproteins. Lipolysis was carried out in vitro using lipoprotein lipase purified from bovine milk, and mixtures with or without plasma. Lipoproteins were isolated by ultracentrifugation and by gel filtration. Labeled apo-C-II and apo-C-III-1 distributed among plasma lipoproteins, predominantly VLDL and high density lipoprotein (HDL). Lipolysis induced transfer of apo-C-II and apo-C-III-1 from VLDL to HDL. The transfer was proportional to the extent of triglyceride hydrolysis, and similar for the two apoproteins. The apo-C-II/apo-C-III-1 radioactivity ratio did not change in either VLDL or the fraction of d greater than 1.006 g/ml during the progression of the lipolytic process. Similar observations were recorded while using plasma-devoid lipolytic systems. Gel filtration of incubation mixtures, on 6% agarose, revealed that the removal of labeled apo-C molecules from VLDL is not a consequence of either centrifugation or high salt concentration. These results suggest that there is no preferential removal of apo-C-II or apo-C-III-1 from lipolyzed VLDL particles. They further indicate that the ratio of apo-C-II to apo-C-III-1 does not regulate the extent of lipolysis of different VLDL particles, at least in VLDL isolated from normolipidemic humans.", "contents": "Very low density lipoprotein. Removal of Apolipoproteins C-II and C-III-1 during lipolysis in vitro. In this study we have investigated the effects of very low density lipoprotein (VLDL) lipolysis on the removal of radiolabeled apolipoprotein C-II and apolipoprotein C-III-1 from in vitro lipolyzed lipoproteins. Lipolysis was carried out in vitro using lipoprotein lipase purified from bovine milk, and mixtures with or without plasma. Lipoproteins were isolated by ultracentrifugation and by gel filtration. Labeled apo-C-II and apo-C-III-1 distributed among plasma lipoproteins, predominantly VLDL and high density lipoprotein (HDL). Lipolysis induced transfer of apo-C-II and apo-C-III-1 from VLDL to HDL. The transfer was proportional to the extent of triglyceride hydrolysis, and similar for the two apoproteins. The apo-C-II/apo-C-III-1 radioactivity ratio did not change in either VLDL or the fraction of d greater than 1.006 g/ml during the progression of the lipolytic process. Similar observations were recorded while using plasma-devoid lipolytic systems. Gel filtration of incubation mixtures, on 6% agarose, revealed that the removal of labeled apo-C molecules from VLDL is not a consequence of either centrifugation or high salt concentration. These results suggest that there is no preferential removal of apo-C-II or apo-C-III-1 from lipolyzed VLDL particles. They further indicate that the ratio of apo-C-II to apo-C-III-1 does not regulate the extent of lipolysis of different VLDL particles, at least in VLDL isolated from normolipidemic humans."}
{"id": "PMID:227905", "title": "A new system for studying molecular mechanisms of mutation by carcinogens.", "content": "A new system for studying the molecular mechanisms of mutation by carcinogens is described. The system involves (a) site-specific modification of the essential gene G in phi X174 replicative form DNA by a combination of chemical and enzymatic steps; (b) production of mutant virus carrying a change at a single preselected site by transfection of spheroplasts with the site modified phi X174 DNA; (c) detection and propagation of mutants using a host carrying the plasmid, p phi XG, that rescues all type of gene G mutants by complementation; (d) identification of the mutation in the progeny virus by isolating and sequencing mutant phi X174 DNA in the region that carried the parental, site-specific change. To demonstrate that this system is operational, we have produced a previously unknown phi X174 gene G mutant carrying a C leads to T base change at position 2401 of the viral (plus) strand. This preplanned, nonsense (amber) mutant was obtained by changing G to A at the appropriate position in a chemically synthesized, octadeoxynucleotide, minus strand primer; elongating this enzymatically with Escherichia coli DNA polymerase I (larger fragment) (lacking 5' leads to 3' exonuclease activity) to a 17-mer; and repriming to obtain the site-modified phi X174 replicative form DNA enzymatically with E. coli DNA polymerase I (large fragment) and T4 DNA ligase. After transfection of spheroplasts with the heteroduplex DNA, the lysate was screened for mutant virus with permissive (carrying p phi XG) and nonpermissive (without p phi XG) host cells. About 1% of the progeny virus were mutants. Out of 15 isolates, 11 were suppressible by an amber Su1+ (serine) or an ochre Su8+ (glutamine) suppressor. The other 4 isolates were not suppressed at all. Replicative form DNA produced from one of the suppressible mutants was shown (by sequencing) to contain the expected C leads to T change at the preselected site in the viral strand. Replicative form DNA from one of the nonsuppressible mutants was partially sequenced. No change was found at or around position 2401. The nature of the mutation(s) in these isolates is still unknown. The occurrence of mutations outside the preselected sites represent a potential problem for our projected studies, but additional data is required before the problem can be fully evaluated. In spite of this, it should be possible to study, in vivo, the biological effects of any site-specific modification (including covalent modifications by carcinogens) that can be introduced into gene G of phi X174 DNA via a synthetic, oligonucleotide primer.", "contents": "A new system for studying molecular mechanisms of mutation by carcinogens. A new system for studying the molecular mechanisms of mutation by carcinogens is described. The system involves (a) site-specific modification of the essential gene G in phi X174 replicative form DNA by a combination of chemical and enzymatic steps; (b) production of mutant virus carrying a change at a single preselected site by transfection of spheroplasts with the site modified phi X174 DNA; (c) detection and propagation of mutants using a host carrying the plasmid, p phi XG, that rescues all type of gene G mutants by complementation; (d) identification of the mutation in the progeny virus by isolating and sequencing mutant phi X174 DNA in the region that carried the parental, site-specific change. To demonstrate that this system is operational, we have produced a previously unknown phi X174 gene G mutant carrying a C leads to T base change at position 2401 of the viral (plus) strand. This preplanned, nonsense (amber) mutant was obtained by changing G to A at the appropriate position in a chemically synthesized, octadeoxynucleotide, minus strand primer; elongating this enzymatically with Escherichia coli DNA polymerase I (larger fragment) (lacking 5' leads to 3' exonuclease activity) to a 17-mer; and repriming to obtain the site-modified phi X174 replicative form DNA enzymatically with E. coli DNA polymerase I (large fragment) and T4 DNA ligase. After transfection of spheroplasts with the heteroduplex DNA, the lysate was screened for mutant virus with permissive (carrying p phi XG) and nonpermissive (without p phi XG) host cells. About 1% of the progeny virus were mutants. Out of 15 isolates, 11 were suppressible by an amber Su1+ (serine) or an ochre Su8+ (glutamine) suppressor. The other 4 isolates were not suppressed at all. Replicative form DNA produced from one of the suppressible mutants was shown (by sequencing) to contain the expected C leads to T change at the preselected site in the viral strand. Replicative form DNA from one of the nonsuppressible mutants was partially sequenced. No change was found at or around position 2401. The nature of the mutation(s) in these isolates is still unknown. The occurrence of mutations outside the preselected sites represent a potential problem for our projected studies, but additional data is required before the problem can be fully evaluated. In spite of this, it should be possible to study, in vivo, the biological effects of any site-specific modification (including covalent modifications by carcinogens) that can be introduced into gene G of phi X174 DNA via a synthetic, oligonucleotide primer."}
{"id": "PMID:227909", "title": "Total resection of distal femur or proximal tibia for bone tumours. Autogenous bone grafts and arthrodesis in twenty-six cases.", "content": "Resection of the distal femur or proximal tibia en bloc has been performed on twenty-six patients with primary bone tumours. The gap was filled with autogenous bone grafts stabilised with a long intramedullary nail, thus arthrodesing the knee. In two cases temporary stabilisation with a K\u00fcntscher rod and acrylic cement was adopted because of adjuvant chemotherapy. Union was achieved in twenty-four cases (92 per cent). Infection was the main and practically the only major complication, occurring in five (19 per cent) of the cases: it healed with union in three, healed with non-union in one, and led to an above-knee amputation in the fifth case. Follow-up has been from one to eight years with an average of four years.", "contents": "Total resection of distal femur or proximal tibia for bone tumours. Autogenous bone grafts and arthrodesis in twenty-six cases. Resection of the distal femur or proximal tibia en bloc has been performed on twenty-six patients with primary bone tumours. The gap was filled with autogenous bone grafts stabilised with a long intramedullary nail, thus arthrodesing the knee. In two cases temporary stabilisation with a K\u00fcntscher rod and acrylic cement was adopted because of adjuvant chemotherapy. Union was achieved in twenty-four cases (92 per cent). Infection was the main and practically the only major complication, occurring in five (19 per cent) of the cases: it healed with union in three, healed with non-union in one, and led to an above-knee amputation in the fifth case. Follow-up has been from one to eight years with an average of four years."}
{"id": "PMID:227910", "title": "Development of second malignancies in rats after cure of acute leukemia L 5222 by single doses of 2-chloroethylnitrosoureas.", "content": "After cure of rat leukemia L 5222 in 79 BD IX rats by single doses of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or 1-(2-hydroxyethyl)-3-(2-chloroethyl)-3-nitrosourea (Hydroxyethyl-CNU) a total of 9 rats (11%) developed secondary malignomas.", "contents": "Development of second malignancies in rats after cure of acute leukemia L 5222 by single doses of 2-chloroethylnitrosoureas. After cure of rat leukemia L 5222 in 79 BD IX rats by single doses of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or 1-(2-hydroxyethyl)-3-(2-chloroethyl)-3-nitrosourea (Hydroxyethyl-CNU) a total of 9 rats (11%) developed secondary malignomas."}
{"id": "PMID:227912", "title": "Subcellular distribution in cerebral cortex of two proteins phosphorylated by a cAMP-dependent protein kinase.", "content": "The subcellular distribution of Proteins Ia and Ib, two proteins which serve as specific substrates for protein kinases present in mammalian brain, was studied in the dog cerebral cortex. Proteins Ia and Ib were found to be most highly enriched in synaptic vesicle fractions; they were also present in postsynaptic density and synaptic membrane fractions in significant amounts. Proteins Ia and Ib present in the synaptic vesicle fraction appear to be similar, if not identical, to those present in the postsynaptic density fraction as judged by several criteria: (a) the ability to serve as substrate for cAMP-dependent protein kinase, (b) electrophoretic mobility in the presence of sodium dodecyl sulfate, (c) extractability with NH4Cl or EGTA, and (d) fragmentation to electrophoretically similar peptides by a purified Staphylococcus aureus protease. In addition, the postsynaptic density fraction has been found to contain cAMP-dependent Protein Ia and Protein Ib kinase activity. The subcellular localization of Proteins Ia and Ib suggests a role for these proteins in the physiology of the synapse.", "contents": "Subcellular distribution in cerebral cortex of two proteins phosphorylated by a cAMP-dependent protein kinase. The subcellular distribution of Proteins Ia and Ib, two proteins which serve as specific substrates for protein kinases present in mammalian brain, was studied in the dog cerebral cortex. Proteins Ia and Ib were found to be most highly enriched in synaptic vesicle fractions; they were also present in postsynaptic density and synaptic membrane fractions in significant amounts. Proteins Ia and Ib present in the synaptic vesicle fraction appear to be similar, if not identical, to those present in the postsynaptic density fraction as judged by several criteria: (a) the ability to serve as substrate for cAMP-dependent protein kinase, (b) electrophoretic mobility in the presence of sodium dodecyl sulfate, (c) extractability with NH4Cl or EGTA, and (d) fragmentation to electrophoretically similar peptides by a purified Staphylococcus aureus protease. In addition, the postsynaptic density fraction has been found to contain cAMP-dependent Protein Ia and Protein Ib kinase activity. The subcellular localization of Proteins Ia and Ib suggests a role for these proteins in the physiology of the synapse."}
{"id": "PMID:227913", "title": "Involvement of microtubules and 10-nm filaments in the movement and positioning of nuclei in syncytia.", "content": "Previous studies (Holmes, K.V., and P.W. Choppin. J. Exp. Med. 124:501-520; J. Cell Biol. 39:526-543) showed that infection of baby hamster kidney (BHK21-F) cells with the parainfluenza virus SV5 causes extensive cell fusion, that nuclei migrate in the syncytial cytoplasm and align in tightly-packed rows, and that microtubules are involved in nuclear movement and alignment. The role of microtubules, 10-nm filaments, and actin-containing microfilaments in this process has been investigated by immunofluorescence microscopy using specific antisera, time-lapse cinematography, and electron microscopy. During cell fusion, micro tubules and 10-nm filaments from many cells form large bundles which are localized between rows of nuclei. No organized bundles of actin fibers were detected in these areas, although actin fibers were observed in regions away from the aligned nuclei. Although colchicine disrupts microtubules and inhibits nuclear movement, cytochalasin B (CB; 20-50 microgram/ml) does not inhibit cell fusion or nuclear movement. However, CB alters the shape of the syncytium, resulting in long filamentous processes extending from a central region. When these processes from neighboring cells make contact, fusion occurs, and nuclei migrate through the channels which are formed. Electron and immunofluorescence microscopy reveal bundles of microtubules and 10-nm filaments in parallel arrays within these processes, but no bundles of microfilaments were detected. The effect of CB on the structural integrity of microfilaments at this high concentration (20 microgram/ml) was demonstrated by the disappearance of filaments interacting with heavy meromyosin. Cycloheximide (20 microgram/ml) inhibits protein synthesis but does not affect cell fusion, the formation of microtubules and 10-nm filament bundles, or nuclear migration and alignment; thus, continued protein synthesis is not required. The association of microtubules and 10-nm filaments with nuclear migration and alignment suggests that microtubules and 10-nm filaments are two components in a system which serves both cytoskeletal and force-generating functions in intracellular movement and position of nuclei.", "contents": "Involvement of microtubules and 10-nm filaments in the movement and positioning of nuclei in syncytia. Previous studies (Holmes, K.V., and P.W. Choppin. J. Exp. Med. 124:501-520; J. Cell Biol. 39:526-543) showed that infection of baby hamster kidney (BHK21-F) cells with the parainfluenza virus SV5 causes extensive cell fusion, that nuclei migrate in the syncytial cytoplasm and align in tightly-packed rows, and that microtubules are involved in nuclear movement and alignment. The role of microtubules, 10-nm filaments, and actin-containing microfilaments in this process has been investigated by immunofluorescence microscopy using specific antisera, time-lapse cinematography, and electron microscopy. During cell fusion, micro tubules and 10-nm filaments from many cells form large bundles which are localized between rows of nuclei. No organized bundles of actin fibers were detected in these areas, although actin fibers were observed in regions away from the aligned nuclei. Although colchicine disrupts microtubules and inhibits nuclear movement, cytochalasin B (CB; 20-50 microgram/ml) does not inhibit cell fusion or nuclear movement. However, CB alters the shape of the syncytium, resulting in long filamentous processes extending from a central region. When these processes from neighboring cells make contact, fusion occurs, and nuclei migrate through the channels which are formed. Electron and immunofluorescence microscopy reveal bundles of microtubules and 10-nm filaments in parallel arrays within these processes, but no bundles of microfilaments were detected. The effect of CB on the structural integrity of microfilaments at this high concentration (20 microgram/ml) was demonstrated by the disappearance of filaments interacting with heavy meromyosin. Cycloheximide (20 microgram/ml) inhibits protein synthesis but does not affect cell fusion, the formation of microtubules and 10-nm filament bundles, or nuclear migration and alignment; thus, continued protein synthesis is not required. The association of microtubules and 10-nm filaments with nuclear migration and alignment suggests that microtubules and 10-nm filaments are two components in a system which serves both cytoskeletal and force-generating functions in intracellular movement and position of nuclei."}
{"id": "PMID:227914", "title": "Immunofluorescence and electron microscopy of the cytoplasmic surface of the human erythrocyte membrane and its interaction with Sendai virus.", "content": "A method was developed for directly observing the inner surfaces of plasma membranes by light and electron microscopy. Human erythrocytes were attached to cover slips (glass or mica) treated with aminopropylsilane and glutaraldehyde, and then disrupted by direct application of a jet of buffer, which removed the distal portion of the cells, thus exposing the cytoplasmic surface (PS) of the flattened membranes. Antispectrin antibodies and Sendai virus particles were employed as sensitive markers for, respectively, the PS and the external surface (ES) of the membrane; their localization by immunofluorescence or electron microscopy demonstrated that the major asymmetrical features of the plasma membrane were preserved. The fusion of Sendai virus particles with cells was investigated using double-labeling immunofluorescence techniques. Virus adsorbed to the ES of cells at 4 degrees C was not accessible to fluorescein-labeled antibodies applied from the PS side. After incubation at 37 degrees C, viral antigens could be detected at the PS. These antigens, however, remained localized and did not diffuse from the site of attachment, as is usually seen in viral antigens accessible on the ES. They may therefore represent internal viral antigens not incorporated into the plasma membrane as a result of virus-cell fusion.", "contents": "Immunofluorescence and electron microscopy of the cytoplasmic surface of the human erythrocyte membrane and its interaction with Sendai virus. A method was developed for directly observing the inner surfaces of plasma membranes by light and electron microscopy. Human erythrocytes were attached to cover slips (glass or mica) treated with aminopropylsilane and glutaraldehyde, and then disrupted by direct application of a jet of buffer, which removed the distal portion of the cells, thus exposing the cytoplasmic surface (PS) of the flattened membranes. Antispectrin antibodies and Sendai virus particles were employed as sensitive markers for, respectively, the PS and the external surface (ES) of the membrane; their localization by immunofluorescence or electron microscopy demonstrated that the major asymmetrical features of the plasma membrane were preserved. The fusion of Sendai virus particles with cells was investigated using double-labeling immunofluorescence techniques. Virus adsorbed to the ES of cells at 4 degrees C was not accessible to fluorescein-labeled antibodies applied from the PS side. After incubation at 37 degrees C, viral antigens could be detected at the PS. These antigens, however, remained localized and did not diffuse from the site of attachment, as is usually seen in viral antigens accessible on the ES. They may therefore represent internal viral antigens not incorporated into the plasma membrane as a result of virus-cell fusion."}
{"id": "PMID:227915", "title": "Association of glycogen synthase phosphatase and phosphorylase phosphatase activities with membranes of hepatic smooth endoplasmic reticulum.", "content": "A detailed investigation was conducted to determine the precise subcellular localization of the rate-limiting enzymes of hepatic glycogen metabolism (glycogen synthase and phosphorylase) and their regulatory enzymes (synthase phosphatase and phosphorylase phosphatase). Rat liver was homogenized and fractionated to produce soluble, rough and smooth microsomal fractions. Enzyme assays of the fractions were performed, and the results showed that glycogen synthase and phosphorylase were located in the soluble fraction of the livers. Synthase phosphatase and phosphorylase phosphatase activities were also present in soluble fractions, but were clearly identified in both rough and smooth microsomal fractions. It is suggested that the location of smooth endoplasmic reticulum (SER) within the cytosome forms a microenvironment within hepatocytes that establishes conditions necessary for glycogen synthesis (and degradation). Thus the location of SER in the cell determines regions of the hepatocyte that are rich in glycogen particles. Furthermore, the demonstration of the association of synthase phosphatase and phosphorylase phosphatase with membranes of SER may account for the close morphological association of SER with glycogen particles (i.e., disposition of SER membranes brings the membrane-bound regulatory enzymes in close contact with their substrates).", "contents": "Association of glycogen synthase phosphatase and phosphorylase phosphatase activities with membranes of hepatic smooth endoplasmic reticulum. A detailed investigation was conducted to determine the precise subcellular localization of the rate-limiting enzymes of hepatic glycogen metabolism (glycogen synthase and phosphorylase) and their regulatory enzymes (synthase phosphatase and phosphorylase phosphatase). Rat liver was homogenized and fractionated to produce soluble, rough and smooth microsomal fractions. Enzyme assays of the fractions were performed, and the results showed that glycogen synthase and phosphorylase were located in the soluble fraction of the livers. Synthase phosphatase and phosphorylase phosphatase activities were also present in soluble fractions, but were clearly identified in both rough and smooth microsomal fractions. It is suggested that the location of smooth endoplasmic reticulum (SER) within the cytosome forms a microenvironment within hepatocytes that establishes conditions necessary for glycogen synthesis (and degradation). Thus the location of SER in the cell determines regions of the hepatocyte that are rich in glycogen particles. Furthermore, the demonstration of the association of synthase phosphatase and phosphorylase phosphatase with membranes of SER may account for the close morphological association of SER with glycogen particles (i.e., disposition of SER membranes brings the membrane-bound regulatory enzymes in close contact with their substrates)."}
{"id": "PMID:227916", "title": "Subcellular localization of DNA-binding protein BA by immunofluorescence and immunoelectron microscopy.", "content": "Nonhistone protein BA has been shown to decrease in amount in the chromatin of growth- stimulated normal rat liver (Yeoman et al. 1975. Cancer Res. 35:1249-1255) and in mitogen-stimulated normal human lymphocytes (Yeoman et al. 1976. Exp. Cell Res. 100:47- 55.). Subsequently, protein BA was purified and was shown to prefer to bind to double- stranded A-T-rich DNAs (Catino et al. 1978. Biochemistry. 17:983-987.). Immunization of rabbits with highly purified protein BA has resulted in the production of a specific antibody. A specific immunoreactivity for chromosomal protein BA has been demonstrated by immunoelectrophoresis and double antibody immunoprecipitation analysis with rabbit anti-BA immunoglobulin and IgG fractions. Light microscope examination of normal rat liver crysections by the indirect immunofluorescence procedure has demonstrated a cytoplasmic as well as a nuclear localization for protein BA with a pronounced perinucleolar fluorescence. Immunoelectron microscopy employing the peroxidase antiperoxidase method of antigen localization has confirmed the immunofluorescence data and has show a heterochromatin localization for protein BA. The relationship of the localization of protein BA to gene control in quiescent cells or to configurations of heterochromatin as well as the marked reduction in the amounts of protein BA which occur in stimulated growth states remains to be defined.", "contents": "Subcellular localization of DNA-binding protein BA by immunofluorescence and immunoelectron microscopy. Nonhistone protein BA has been shown to decrease in amount in the chromatin of growth- stimulated normal rat liver (Yeoman et al. 1975. Cancer Res. 35:1249-1255) and in mitogen-stimulated normal human lymphocytes (Yeoman et al. 1976. Exp. Cell Res. 100:47- 55.). Subsequently, protein BA was purified and was shown to prefer to bind to double- stranded A-T-rich DNAs (Catino et al. 1978. Biochemistry. 17:983-987.). Immunization of rabbits with highly purified protein BA has resulted in the production of a specific antibody. A specific immunoreactivity for chromosomal protein BA has been demonstrated by immunoelectrophoresis and double antibody immunoprecipitation analysis with rabbit anti-BA immunoglobulin and IgG fractions. Light microscope examination of normal rat liver crysections by the indirect immunofluorescence procedure has demonstrated a cytoplasmic as well as a nuclear localization for protein BA with a pronounced perinucleolar fluorescence. Immunoelectron microscopy employing the peroxidase antiperoxidase method of antigen localization has confirmed the immunofluorescence data and has show a heterochromatin localization for protein BA. The relationship of the localization of protein BA to gene control in quiescent cells or to configurations of heterochromatin as well as the marked reduction in the amounts of protein BA which occur in stimulated growth states remains to be defined."}
{"id": "PMID:227917", "title": "Effect of enzymes on rotavirus infectivity.", "content": "The infectivity of a bovine rotavirus was enhanced 140-, 8-, and 3-fold, respectively, by trypsin, protease, and lactase. Ficin, carboxypeptidases A and B, lysozyme, and beta-galactosidase had little effect on the infectivity. Chymotrypsin caused a threefold decrease in the infectivity. Trypsin acts directly on the rotavirus and not on the host cell.", "contents": "Effect of enzymes on rotavirus infectivity. The infectivity of a bovine rotavirus was enhanced 140-, 8-, and 3-fold, respectively, by trypsin, protease, and lactase. Ficin, carboxypeptidases A and B, lysozyme, and beta-galactosidase had little effect on the infectivity. Chymotrypsin caused a threefold decrease in the infectivity. Trypsin acts directly on the rotavirus and not on the host cell."}
{"id": "PMID:227918", "title": "Neutralization of human serum beta-lysin by sodium polyanetholsulfonate and sodium amylosulfate.", "content": "Normal fresh and heat-inactivated (56 degrees C, 30 min) human sera (80 vol%, i.e., 80% [vol/vol] of a 2-ml assay volume) killed Bacillus subtilis ATCC 6633 cell inocula of 1.5 x 10(4) colony-forming units per ml within 1 to 2 h after exposure. The B. subtilis assay strain proved slightly and reversibly susceptible to 5 mug of egg white lysozyme per ml. Seitz filtration of fresh human serum completely removed beta-lysin activity; significant amounts of serum lysozyme were removed as well, as determined with the bioassay strain Micrococcus lysodeikticus ATCC 4698. However, bactericidal activity of human serum via classical or alternative complement pathway activation remained intact. Addition of 0.01 M dithiothreitol to fresh human serum abolished beta-lysin activity, but not that of serum lysozyme. Chelation of fresh and heat-inactivated human serum with 0.01 M MgCl(2) + 0.01 M ethylene glycol tetraacetic acid, but not with 0.01 M ethylenediaminetetraacetic acid, markedly retarded beta-lysin activity; however, lysozyme activity remained unaffected. Chelation of serum with 0.01 M MgCl(2) + 0.01 M ethylene glycol tetraacetic acid + 0.01 M CaCl(2) completely abrogated beta-lysin activity, but not that of lysozyme. Absorption of human serum with 10 mg of bentonite per ml (10 min, 37 degrees C) completely removed beta-lysin and lysozyme activity, but failed to affect serum bactericidal activity against Escherichia coli control strain C. Reconstitution of 50 vol% of bentonite-absorbed serum with 40 vol% of heat-inactivated human serum restored both beta-lysin and lysozyme activity. Addition of either 63 to 500 mug of sodium polyanetholsulfonate per ml or 63 to 500 mug of sodium amylosulfate per ml to 80 vol% of fresh human serum completely neutralized beta-lysin activity for the entire observation period of 22 h.", "contents": "Neutralization of human serum beta-lysin by sodium polyanetholsulfonate and sodium amylosulfate. Normal fresh and heat-inactivated (56 degrees C, 30 min) human sera (80 vol%, i.e., 80% [vol/vol] of a 2-ml assay volume) killed Bacillus subtilis ATCC 6633 cell inocula of 1.5 x 10(4) colony-forming units per ml within 1 to 2 h after exposure. The B. subtilis assay strain proved slightly and reversibly susceptible to 5 mug of egg white lysozyme per ml. Seitz filtration of fresh human serum completely removed beta-lysin activity; significant amounts of serum lysozyme were removed as well, as determined with the bioassay strain Micrococcus lysodeikticus ATCC 4698. However, bactericidal activity of human serum via classical or alternative complement pathway activation remained intact. Addition of 0.01 M dithiothreitol to fresh human serum abolished beta-lysin activity, but not that of serum lysozyme. Chelation of fresh and heat-inactivated human serum with 0.01 M MgCl(2) + 0.01 M ethylene glycol tetraacetic acid, but not with 0.01 M ethylenediaminetetraacetic acid, markedly retarded beta-lysin activity; however, lysozyme activity remained unaffected. Chelation of serum with 0.01 M MgCl(2) + 0.01 M ethylene glycol tetraacetic acid + 0.01 M CaCl(2) completely abrogated beta-lysin activity, but not that of lysozyme. Absorption of human serum with 10 mg of bentonite per ml (10 min, 37 degrees C) completely removed beta-lysin and lysozyme activity, but failed to affect serum bactericidal activity against Escherichia coli control strain C. Reconstitution of 50 vol% of bentonite-absorbed serum with 40 vol% of heat-inactivated human serum restored both beta-lysin and lysozyme activity. Addition of either 63 to 500 mug of sodium polyanetholsulfonate per ml or 63 to 500 mug of sodium amylosulfate per ml to 80 vol% of fresh human serum completely neutralized beta-lysin activity for the entire observation period of 22 h."}
{"id": "PMID:227919", "title": "Variable neutralization of several nonspecific antibacterial systems in fresh, defibrinated human blood by sodium polyanetholsulfonate and sodium amylosulfate.", "content": "Fresh, defibrinated human blood (80 vol%, i.e., 80% [vol/vol] of a 2-ml final assay volume) from two healthy adult donors killed \"delayed serum-sensitive\" (DSS) and \"promptly serum-sensitive\" (PSS) strains of Serratia marcescens, PSS control strain Escherichia coli C, Bacillus subtilis strain ATCC 6633, and Micrococcus lysodeikticus ATCC 4698 in a kinetic manner comparable to that of fresh human serum (80 vol%). However, heat-inactivated (56 degrees C, 30 min), defibrinated human blood revealed markedly reduced or a total lack of beta-lysin activity against the B. subtilis assay strain. Similarly, lysozyme activity of defibrinated blood was diminished somewhat by heat treatment, as determined with the M. lysodeikticus assay strain. Addition of 500 mug of sodium polyanetholsulfonate (SPS) per ml to 80 vol% of fresh, defibrinated human blood completely neutralized blood bactericidal activity against all assay strains of S. marcescens, E. coli C, and B. subtilis; however, SPS at this concentration failed to abolish lysozyme activity for prolonged periods of incubation. Addition of 500 mug of sodium amylosulfate (SAS) per ml to 80 vol% of fresh defibtinated human blood resulted in protection of cell inocula of DSS strains of S. marcescens only; SAS failed to protect cell inocula of the PSS strains of S. marcescens, E. coli C, B. subtilis, and M. lysodeikticus for extended periods of observation. Based on these data, it is recommended that blood culture specimens that are first drawn into specimen containers (such as Vacutainer tubes or the like) at the patient's bedside, and which contain >/=250 mug of SPS per ml, be diluted into suitable broth media with at least >/=250 mug of SPS per ml by the receiving laboratory within 2 to 4 h after procurement of the specimen. This procedure would ensure continued, adequate neutralization of the specimen's inherent beta-lysin, lysozyme, and complement- and antibody-mediated bactericidal activities.", "contents": "Variable neutralization of several nonspecific antibacterial systems in fresh, defibrinated human blood by sodium polyanetholsulfonate and sodium amylosulfate. Fresh, defibrinated human blood (80 vol%, i.e., 80% [vol/vol] of a 2-ml final assay volume) from two healthy adult donors killed \"delayed serum-sensitive\" (DSS) and \"promptly serum-sensitive\" (PSS) strains of Serratia marcescens, PSS control strain Escherichia coli C, Bacillus subtilis strain ATCC 6633, and Micrococcus lysodeikticus ATCC 4698 in a kinetic manner comparable to that of fresh human serum (80 vol%). However, heat-inactivated (56 degrees C, 30 min), defibrinated human blood revealed markedly reduced or a total lack of beta-lysin activity against the B. subtilis assay strain. Similarly, lysozyme activity of defibrinated blood was diminished somewhat by heat treatment, as determined with the M. lysodeikticus assay strain. Addition of 500 mug of sodium polyanetholsulfonate (SPS) per ml to 80 vol% of fresh, defibrinated human blood completely neutralized blood bactericidal activity against all assay strains of S. marcescens, E. coli C, and B. subtilis; however, SPS at this concentration failed to abolish lysozyme activity for prolonged periods of incubation. Addition of 500 mug of sodium amylosulfate (SAS) per ml to 80 vol% of fresh defibtinated human blood resulted in protection of cell inocula of DSS strains of S. marcescens only; SAS failed to protect cell inocula of the PSS strains of S. marcescens, E. coli C, B. subtilis, and M. lysodeikticus for extended periods of observation. Based on these data, it is recommended that blood culture specimens that are first drawn into specimen containers (such as Vacutainer tubes or the like) at the patient's bedside, and which contain >/=250 mug of SPS per ml, be diluted into suitable broth media with at least >/=250 mug of SPS per ml by the receiving laboratory within 2 to 4 h after procurement of the specimen. This procedure would ensure continued, adequate neutralization of the specimen's inherent beta-lysin, lysozyme, and complement- and antibody-mediated bactericidal activities."}
{"id": "PMID:227920", "title": "Comparison of different tissue cultures for isolation and quantitation of influenza and parainfluenza viruses.", "content": "Rhesus and cynomolgus monkey kidney tissue cultures and two continuous lines, Madin-Darby canine kidney (MDCK) and LLC-MK2, were compared in titrations and isolations of influenza and parainfluenza viruses. Tube cultures were inoculated with laboratory virus strains or stored patient specimens and observed for hemadsorption. Trypsin was added to the medium of the continuous lines to increase sensitivity. All four tissue cultures gave similar titers of influenza A/USSR (H1N1), A/Texas (H3N2), and B/HK, but lower titers of parainfluenza 1, 2, and 3 were observed with MDCK. Cynomolgus kidney was the best single tissue culture for reisolation of the six viruses, but foamy-virus contamination of many lots was a serious problem. Reisolation of influenza viruses was as successful with MDCK as with primary monkey kidney. LLC-MK2 was similar to rhesus kidney but less successful than cynomolgus kidney. For reisolation of parainfluenza viruses, LLC-MK2 was superior to rhesus monkey kidney and similar to cynomolgus kidney. MDCK was less useful for parainfluenza viruses. Thus, LLC-MK2 would be an acceptable single tissue alternative to primary monkey kidney. The combination of MDCK and LLC-MK2 would provide optimal sensitivity for isolation of all six viruses.", "contents": "Comparison of different tissue cultures for isolation and quantitation of influenza and parainfluenza viruses. Rhesus and cynomolgus monkey kidney tissue cultures and two continuous lines, Madin-Darby canine kidney (MDCK) and LLC-MK2, were compared in titrations and isolations of influenza and parainfluenza viruses. Tube cultures were inoculated with laboratory virus strains or stored patient specimens and observed for hemadsorption. Trypsin was added to the medium of the continuous lines to increase sensitivity. All four tissue cultures gave similar titers of influenza A/USSR (H1N1), A/Texas (H3N2), and B/HK, but lower titers of parainfluenza 1, 2, and 3 were observed with MDCK. Cynomolgus kidney was the best single tissue culture for reisolation of the six viruses, but foamy-virus contamination of many lots was a serious problem. Reisolation of influenza viruses was as successful with MDCK as with primary monkey kidney. LLC-MK2 was similar to rhesus kidney but less successful than cynomolgus kidney. For reisolation of parainfluenza viruses, LLC-MK2 was superior to rhesus monkey kidney and similar to cynomolgus kidney. MDCK was less useful for parainfluenza viruses. Thus, LLC-MK2 would be an acceptable single tissue alternative to primary monkey kidney. The combination of MDCK and LLC-MK2 would provide optimal sensitivity for isolation of all six viruses."}
{"id": "PMID:227921", "title": "Improved indirect hemagglutination test for cytomegalovirus using human O erythrocytes in lysine.", "content": "A modified indirect hemagglutination test for cytomegalovirus antibodies is described in which glutaraldehyde-fixed human O cells, rather than sheep cells, are used. Nonspecific hemagglutination was reduced by use of the optimal tannic acid concentration for each cell batch and the addition of 0.1 M lysine to the phosphate-buffered saline in which the fixed, tanned, sensitized cells were resuspended for use in the test. Three of 349 sera showed nonspecific hemagglutination by this technique. Antigen made by freezing phosphate-buffered saline (pH 7.2) over an infected monolayer can be used at dilutions of 1:8 to 1:15. Fixed, tanned, sensitized cells ready for use in the test can be stored in liquid nitrogen for up to 8 months. Use of cryoprotectants and washing after thawing is unnecessary. Simplification of the assay permits one person to screen 300 sera in 1 day or to determine the immune status of a potential donor or recipient in 45 min after the test is set up. The modified assay compares favorably in sensitivity with the complement fixation test and with previously described methods for performing the indirect hemagglutination test.", "contents": "Improved indirect hemagglutination test for cytomegalovirus using human O erythrocytes in lysine. A modified indirect hemagglutination test for cytomegalovirus antibodies is described in which glutaraldehyde-fixed human O cells, rather than sheep cells, are used. Nonspecific hemagglutination was reduced by use of the optimal tannic acid concentration for each cell batch and the addition of 0.1 M lysine to the phosphate-buffered saline in which the fixed, tanned, sensitized cells were resuspended for use in the test. Three of 349 sera showed nonspecific hemagglutination by this technique. Antigen made by freezing phosphate-buffered saline (pH 7.2) over an infected monolayer can be used at dilutions of 1:8 to 1:15. Fixed, tanned, sensitized cells ready for use in the test can be stored in liquid nitrogen for up to 8 months. Use of cryoprotectants and washing after thawing is unnecessary. Simplification of the assay permits one person to screen 300 sera in 1 day or to determine the immune status of a potential donor or recipient in 45 min after the test is set up. The modified assay compares favorably in sensitivity with the complement fixation test and with previously described methods for performing the indirect hemagglutination test."}
{"id": "PMID:227922", "title": "Epstein-Barr virus-specific serum immunoglobulin A as an acute-phase antibody in infectious mononucleosis.", "content": "Immunoglobulin A (IgA) antibodies to Epstein-Barr virus viral capsid antigen were assayed serially in 19 patients with infectious mononucleosis and in 38 controls. Seventy-four percent of infectious mononucleosis patients demonstrated IgA antibody, whereas this was found in 13% of controls. This antibody appeared early in infectious mononucleosis and was virtually gone 10 weeks after onset. Comparison of IgA antibody kinetics was made with IgG and IgM antibodies to viral capsid antigen, heterophile antibody, and antibody to Epstein-Barr virus early antigen and nuclear antigen. Failure to demonstrate IgA antibody was associated with severe illness, prolonged illness, delay in IgG and anti-Epstein-Barr virus nuclear antigen antibody, and low or absent heterophile and anti-early antigen antibody. Assay of IgA antibody to viral capsid antigen is a potentially useful adjunct in the serodiagnosis of infectious mononucleosis or recent Epstein-Barr virus infection, as are the other antibodies tested, but in this study IgM viral capsid antigen antibody was the only acute-phase antibody present in all patients.", "contents": "Epstein-Barr virus-specific serum immunoglobulin A as an acute-phase antibody in infectious mononucleosis. Immunoglobulin A (IgA) antibodies to Epstein-Barr virus viral capsid antigen were assayed serially in 19 patients with infectious mononucleosis and in 38 controls. Seventy-four percent of infectious mononucleosis patients demonstrated IgA antibody, whereas this was found in 13% of controls. This antibody appeared early in infectious mononucleosis and was virtually gone 10 weeks after onset. Comparison of IgA antibody kinetics was made with IgG and IgM antibodies to viral capsid antigen, heterophile antibody, and antibody to Epstein-Barr virus early antigen and nuclear antigen. Failure to demonstrate IgA antibody was associated with severe illness, prolonged illness, delay in IgG and anti-Epstein-Barr virus nuclear antigen antibody, and low or absent heterophile and anti-early antigen antibody. Assay of IgA antibody to viral capsid antigen is a potentially useful adjunct in the serodiagnosis of infectious mononucleosis or recent Epstein-Barr virus infection, as are the other antibodies tested, but in this study IgM viral capsid antigen antibody was the only acute-phase antibody present in all patients."}
{"id": "PMID:227923", "title": "Effects of fatty acids on growth of Bordetella pertussis in defined medium.", "content": "The effects of saturated and unsaturated fatty acids on the growth of Bordetella pertussis strain 114 in defined medium were tested. Individual fatty acids were found to be either inhibitory or stimulatory to growth, depending on concentration. Myristic (C14), pentadecanoic (C15), and palmitic (C16) acids were the most inhibitory saturated fatty acids tested. B. pertussis 114 was extremely sensitive to the unsaturated fatty acids oleic (C18; cis-9), elaidic (C18; trans-9) and petroselinic (C18; cis-6).", "contents": "Effects of fatty acids on growth of Bordetella pertussis in defined medium. The effects of saturated and unsaturated fatty acids on the growth of Bordetella pertussis strain 114 in defined medium were tested. Individual fatty acids were found to be either inhibitory or stimulatory to growth, depending on concentration. Myristic (C14), pentadecanoic (C15), and palmitic (C16) acids were the most inhibitory saturated fatty acids tested. B. pertussis 114 was extremely sensitive to the unsaturated fatty acids oleic (C18; cis-9), elaidic (C18; trans-9) and petroselinic (C18; cis-6)."}
{"id": "PMID:227924", "title": "Collagenase in equine cell culture preparation.", "content": "Equine kidney cells disaggregated by treatment with 0.01% collagenase were used in the preparation of primary monolayer cell cultures. The primary cells could be stored for long periods in liquid nitrogen and subsequently subcultivated. These techniques provided a long-term supply of equine kidney cells, free of apparent contamination, from the kidneys of a single fetus.", "contents": "Collagenase in equine cell culture preparation. Equine kidney cells disaggregated by treatment with 0.01% collagenase were used in the preparation of primary monolayer cell cultures. The primary cells could be stored for long periods in liquid nitrogen and subsequently subcultivated. These techniques provided a long-term supply of equine kidney cells, free of apparent contamination, from the kidneys of a single fetus."}
{"id": "PMID:227925", "title": "Skeletal muscle calcium metabolism and contractile force in vitamin D-deficient chicks.", "content": "The myopathy associated with vitamin D deficiency has not been well characterized, and it is not known if weakness is a result of a specific effect of vitamin D deficiency on skeletal muscle. Chicks were raised from hatching on a vitamin D-deficient diet, and by 3 wk of age were hypocalcemic and appeared weak. Tension generated by triceps surae during repetitive stimulation of posterior tibial nerve was significantly less than that developed by chicks given vitamin D(3) supplements (309 g tension/g wet weight of triceps surae, SD 60, for vitamin D-deficient chicks; 470, SD 77, for vitamin D(3)-treated chicks, P < 0.01). Histochemical and electron microscopic examination of skeletal muscles of these chicks showed no abnormalities, and there were no electrophysiologic evidences of motor nerve or neuromuscular junction dysfunction. The concentration of ATP in skeletal muscle of the vitamin D-deficient chicks (5.75 mumol/g wet weight, SD 0.17) was not significantly different from that in vitamin D-treated chicks (5.60, SD 0.50). There was no correlation between strength and serum calcium, serum inorganic phosphate, or skeletal muscle inorganic phosphate. Relaxation of tension after tetanic stimulation was slowed in the vitamin D-deficient chicks (20.6 ms, SD 1.7, vs. 15.4, SD 1.3, in vitamin D-treated chicks and 15.3, SD 1.0, in normal control chicks), and in vitro (45)Ca(++) transport by sarcoplasmic reticulum from the vitamin D-deficient chicks was reduced. Calcium content of mitochondria prepared from leg muscles of vitamin D-deficient chicks (24 nmol/mg mitochondrial protein, SD 6) was considerably lower than that of mitochondria from normal control chicks (45, SD 8) or from chicks treated with vitamin D for 2 wk or more (66-100, depending upon level and duration of therapy). Treatment of the vitamin D-deficient chicks from hatching with sufficient dietary calcium to produce hypercalcemia did not significantly raise skeletal muscle mitochondrial calcium content (31 nmol/mg mitochondrial protein, SD 7) and did not prevent weakness. These studies demonstrate objective weakness as a result of myopathy in vitamin D-deficient chicks, and provide evidence that vitamin D deficiency has effects on skeletal muscle calcium metabolism not secondary to altered plasma concentrations of calcium and phosphate.", "contents": "Skeletal muscle calcium metabolism and contractile force in vitamin D-deficient chicks. The myopathy associated with vitamin D deficiency has not been well characterized, and it is not known if weakness is a result of a specific effect of vitamin D deficiency on skeletal muscle. Chicks were raised from hatching on a vitamin D-deficient diet, and by 3 wk of age were hypocalcemic and appeared weak. Tension generated by triceps surae during repetitive stimulation of posterior tibial nerve was significantly less than that developed by chicks given vitamin D(3) supplements (309 g tension/g wet weight of triceps surae, SD 60, for vitamin D-deficient chicks; 470, SD 77, for vitamin D(3)-treated chicks, P < 0.01). Histochemical and electron microscopic examination of skeletal muscles of these chicks showed no abnormalities, and there were no electrophysiologic evidences of motor nerve or neuromuscular junction dysfunction. The concentration of ATP in skeletal muscle of the vitamin D-deficient chicks (5.75 mumol/g wet weight, SD 0.17) was not significantly different from that in vitamin D-treated chicks (5.60, SD 0.50). There was no correlation between strength and serum calcium, serum inorganic phosphate, or skeletal muscle inorganic phosphate. Relaxation of tension after tetanic stimulation was slowed in the vitamin D-deficient chicks (20.6 ms, SD 1.7, vs. 15.4, SD 1.3, in vitamin D-treated chicks and 15.3, SD 1.0, in normal control chicks), and in vitro (45)Ca(++) transport by sarcoplasmic reticulum from the vitamin D-deficient chicks was reduced. Calcium content of mitochondria prepared from leg muscles of vitamin D-deficient chicks (24 nmol/mg mitochondrial protein, SD 6) was considerably lower than that of mitochondria from normal control chicks (45, SD 8) or from chicks treated with vitamin D for 2 wk or more (66-100, depending upon level and duration of therapy). Treatment of the vitamin D-deficient chicks from hatching with sufficient dietary calcium to produce hypercalcemia did not significantly raise skeletal muscle mitochondrial calcium content (31 nmol/mg mitochondrial protein, SD 7) and did not prevent weakness. These studies demonstrate objective weakness as a result of myopathy in vitamin D-deficient chicks, and provide evidence that vitamin D deficiency has effects on skeletal muscle calcium metabolism not secondary to altered plasma concentrations of calcium and phosphate."}
{"id": "PMID:227926", "title": "Prostaglandin E modulation of the mitogenic response of human T cells. Differential response of T-cell subpopulations.", "content": "Prostaglandins (PG) of the E series, PGE(1) and PGE(2) (PGEs), can induce elevations of intracellular cyclic AMP (cAMP) among thymus-derived (T) lymphocytes (T cells) and inhibit their reactivity. For example, 0.1 muM of PGEs induces a two- to threefold increase of intracellular cAMP among human peripheral blood T cells and a 20-30% suppression of their blastogenic response to phytohemagglutinin. However, this suppression actually represents the net reactivity of T-cell populations demonstrating quite different responses to PGEs. Fractionation of T-enriched populations on a discontinuous density gradient yields a population of high density cells whose phytohemagglutinin-induced blastogenic response is suppressed 60%; a population of intermediate density cells whose response is suppressed 20%; and a population of low density T cells whose response is not suppressed, but is enhanced 20% by both of the PGEs. The diametrically opposite responses of low and high density T cells to the PGEs is not related to any difference in their intrinsic mitogen reactivity nor is it influenced by interactions with other T cells, bone marrow-derived (B) cells, or monocytes. Moreover, the distinct blastogenic response of low and high density T cells to PGEs does not simply correlate with PGE-mediated activation of adenylate cyclase. PGE(2) induced comparable absolute and identical relative increases of intracellular cAMP among the low and high density T cells. Cholera toxin, a potent activator of adenylate cyclase, and exogenous 8-bromo cAMP mimicked the effects of the PGEs on these two T-cell populations. These data demonstrate that T cells are heterogeneous with regard to their response to the PGEs. Thus, PGEs should be considered as potential regulators rather than as universal suppressors for T-cell reactivity. Moreover, the effect of PGEs on the blastogenic response of a given T-cell population depends upon intracellular events which occur subsequent to elevations of cAMP.", "contents": "Prostaglandin E modulation of the mitogenic response of human T cells. Differential response of T-cell subpopulations. Prostaglandins (PG) of the E series, PGE(1) and PGE(2) (PGEs), can induce elevations of intracellular cyclic AMP (cAMP) among thymus-derived (T) lymphocytes (T cells) and inhibit their reactivity. For example, 0.1 muM of PGEs induces a two- to threefold increase of intracellular cAMP among human peripheral blood T cells and a 20-30% suppression of their blastogenic response to phytohemagglutinin. However, this suppression actually represents the net reactivity of T-cell populations demonstrating quite different responses to PGEs. Fractionation of T-enriched populations on a discontinuous density gradient yields a population of high density cells whose phytohemagglutinin-induced blastogenic response is suppressed 60%; a population of intermediate density cells whose response is suppressed 20%; and a population of low density T cells whose response is not suppressed, but is enhanced 20% by both of the PGEs. The diametrically opposite responses of low and high density T cells to the PGEs is not related to any difference in their intrinsic mitogen reactivity nor is it influenced by interactions with other T cells, bone marrow-derived (B) cells, or monocytes. Moreover, the distinct blastogenic response of low and high density T cells to PGEs does not simply correlate with PGE-mediated activation of adenylate cyclase. PGE(2) induced comparable absolute and identical relative increases of intracellular cAMP among the low and high density T cells. Cholera toxin, a potent activator of adenylate cyclase, and exogenous 8-bromo cAMP mimicked the effects of the PGEs on these two T-cell populations. These data demonstrate that T cells are heterogeneous with regard to their response to the PGEs. Thus, PGEs should be considered as potential regulators rather than as universal suppressors for T-cell reactivity. Moreover, the effect of PGEs on the blastogenic response of a given T-cell population depends upon intracellular events which occur subsequent to elevations of cAMP."}
{"id": "PMID:227927", "title": "Vascular and metabolic effects of circulating epinephrine and norepinephrine. Concentration-effect study in dogs.", "content": "Vascular and metabolic effects of circulating epinephrine and norepinephrine have been studied in relation to the plasma concentration of these amines in dogs. Intravenous infusion of epinephrine or norepinephrine (0.1, 0.5, and 2.5 nmol x kg-1 x min-1) raised the plasma concentration of the infused amine by 2.5 , 13, and 63 nM from resting levels of 2.4 and 3.6 nM, respectively. Blood flow to isolated adipose tissue; skeletal muscle preparations; and plasma levels of glycerol, glucose, and cyclic AMP were measured. Epinephrine and norepinephrine displayed a distinct selectivity with regard to both vascular and metabolic effects. Epinephrine caused significant vasoconstriction in adipose tissue already at a plasma concentration of 5 nM, whereas no significant effect was seen on skeletal muscle vascular resistance. Norepinephrine, on the other hand, caused significant vasoconstriction in skeletal muscle at 5 nM but had no vasoconstrictor effect in adipose tissue. Epinephrine was more potent than norepinephrine in increasing plasma cyclic AMP and glucose, whereas the converse was true for plasma glycerol. Epinephrine had significant effects on plasma cyclic AMP at 5 nM and on plasma glucose and glycerol at 15 nM. Norepinephrine, on the other hand, had significant effects on plasma glycerol at 5 nM, plasma cyclic AMP at 15 nM and plasma glucose only at 65 nM. It is suggested that these response patterns are related to a preferential action of epinephrine on beta 2-adrenoceptors and a preferential action of norepinephrine on beta 1-adrenoceptors. Our results support the view that both epinephrine and norepinephrine may act as circulating hormones, because vascular and metabolic effects of both amines were seen at plasma concentrations encountered during various kinds of stress in animals and man.", "contents": "Vascular and metabolic effects of circulating epinephrine and norepinephrine. Concentration-effect study in dogs. Vascular and metabolic effects of circulating epinephrine and norepinephrine have been studied in relation to the plasma concentration of these amines in dogs. Intravenous infusion of epinephrine or norepinephrine (0.1, 0.5, and 2.5 nmol x kg-1 x min-1) raised the plasma concentration of the infused amine by 2.5 , 13, and 63 nM from resting levels of 2.4 and 3.6 nM, respectively. Blood flow to isolated adipose tissue; skeletal muscle preparations; and plasma levels of glycerol, glucose, and cyclic AMP were measured. Epinephrine and norepinephrine displayed a distinct selectivity with regard to both vascular and metabolic effects. Epinephrine caused significant vasoconstriction in adipose tissue already at a plasma concentration of 5 nM, whereas no significant effect was seen on skeletal muscle vascular resistance. Norepinephrine, on the other hand, caused significant vasoconstriction in skeletal muscle at 5 nM but had no vasoconstrictor effect in adipose tissue. Epinephrine was more potent than norepinephrine in increasing plasma cyclic AMP and glucose, whereas the converse was true for plasma glycerol. Epinephrine had significant effects on plasma cyclic AMP at 5 nM and on plasma glucose and glycerol at 15 nM. Norepinephrine, on the other hand, had significant effects on plasma glycerol at 5 nM, plasma cyclic AMP at 15 nM and plasma glucose only at 65 nM. It is suggested that these response patterns are related to a preferential action of epinephrine on beta 2-adrenoceptors and a preferential action of norepinephrine on beta 1-adrenoceptors. Our results support the view that both epinephrine and norepinephrine may act as circulating hormones, because vascular and metabolic effects of both amines were seen at plasma concentrations encountered during various kinds of stress in animals and man."}
{"id": "PMID:227928", "title": "Hepatic secretion of lipoproteins in the rat and the effect of experimental nephrosis.", "content": "Livers from normal and nephrotic rats were perfused by the nonrecirculating technique. Nephrosis was studied on the 7th d after the injection of puromycin animonucleoside. Amino acid-labeled lipoproteins (d < 1.21) were isolated from the perfusion medium by agarose column chromatography or by sequential density ultracentrifugation. In both groups of animals, in addition to very low density lipoproteins and nascent high density lipoproteins, column chromatography revealed the presence of a peak of 2-3 x 10(6) daltons. This peak contained lipoproteins of densities corresponding to <1.006, 1.006 < d < 1.02, and 1.02 < d < 1.06, which indicated that rat liver secretes a heterogeneous mixture of triglyceride-rich lipoproteins. The amount of these lipoprotein density classes was measured and their lipid and apoprotein composition and their apoprotein specific activity were determined. In both groups of rats there was a progressive rise in phospholipid and decrease in triglyceride content as the isolation density increased from 1.006 and 1.06. The lipoproteins from the nephrotics had higher amounts of cholesterol. The livers from the nephrotic rats secreted two to three times as much lipoprotein as controls in all density classes in the first 20 min, but during the next 40 min only the 1.02 < d < 1.06 and nascent high density lipoproteins remained at this high level compared to controls. A larger total liver pool of apolipoproteins in nephrotic livers was inferred from their lower specific activities during the first 20 min. The apoprotein composition of liver perfusate lipoproteins from nephrotics differed from controls. There was a 40% decrease in the amount of low molecular weight apoproteins in all density classes, with corresponding increases in apo B and apo E in the triglyceride-rich fractions. The apo A-1 content of nascent HDL was increased from 16% in controls to 52% in nephrotics, with corresponding decreases in apo C and apo E. When these results were combined with specific activity measurements of the individual apoproteins and the net secretion rate of total protein in each lipoprotein class, it was possible to estimate the total amount of each apoprotein secreted and the total incorporation of labeled amino acids into each. The incorporation of label gave results similar to those obtained by direct measurement of the amounts of apoproteins. Apo E secretion was increased by a factor of 1.8, apo B by 2.8, and apo A-1 by 8.4, whereas the secretion of apo C was not significantly altered. We explain these results by postulating that the primary stimulus to hepatic plasma protein synthesis in response to proteinuria is general and that subsequent negative feedback regulation affects individual apolipoprotein synthesis rates. A corollary of this hypothesis is that the biosynthesis and secretion of an apoprotein may be regulated independently of the lipoprotein density class in which it is found.", "contents": "Hepatic secretion of lipoproteins in the rat and the effect of experimental nephrosis. Livers from normal and nephrotic rats were perfused by the nonrecirculating technique. Nephrosis was studied on the 7th d after the injection of puromycin animonucleoside. Amino acid-labeled lipoproteins (d < 1.21) were isolated from the perfusion medium by agarose column chromatography or by sequential density ultracentrifugation. In both groups of animals, in addition to very low density lipoproteins and nascent high density lipoproteins, column chromatography revealed the presence of a peak of 2-3 x 10(6) daltons. This peak contained lipoproteins of densities corresponding to <1.006, 1.006 < d < 1.02, and 1.02 < d < 1.06, which indicated that rat liver secretes a heterogeneous mixture of triglyceride-rich lipoproteins. The amount of these lipoprotein density classes was measured and their lipid and apoprotein composition and their apoprotein specific activity were determined. In both groups of rats there was a progressive rise in phospholipid and decrease in triglyceride content as the isolation density increased from 1.006 and 1.06. The lipoproteins from the nephrotics had higher amounts of cholesterol. The livers from the nephrotic rats secreted two to three times as much lipoprotein as controls in all density classes in the first 20 min, but during the next 40 min only the 1.02 < d < 1.06 and nascent high density lipoproteins remained at this high level compared to controls. A larger total liver pool of apolipoproteins in nephrotic livers was inferred from their lower specific activities during the first 20 min. The apoprotein composition of liver perfusate lipoproteins from nephrotics differed from controls. There was a 40% decrease in the amount of low molecular weight apoproteins in all density classes, with corresponding increases in apo B and apo E in the triglyceride-rich fractions. The apo A-1 content of nascent HDL was increased from 16% in controls to 52% in nephrotics, with corresponding decreases in apo C and apo E. When these results were combined with specific activity measurements of the individual apoproteins and the net secretion rate of total protein in each lipoprotein class, it was possible to estimate the total amount of each apoprotein secreted and the total incorporation of labeled amino acids into each. The incorporation of label gave results similar to those obtained by direct measurement of the amounts of apoproteins. Apo E secretion was increased by a factor of 1.8, apo B by 2.8, and apo A-1 by 8.4, whereas the secretion of apo C was not significantly altered. We explain these results by postulating that the primary stimulus to hepatic plasma protein synthesis in response to proteinuria is general and that subsequent negative feedback regulation affects individual apolipoprotein synthesis rates. A corollary of this hypothesis is that the biosynthesis and secretion of an apoprotein may be regulated independently of the lipoprotein density class in which it is found."}
{"id": "PMID:227929", "title": "Evidence for skeletal resistance to parathyroid hormone in magnesium deficiency. Studies in isolated perfused bone.", "content": "Hypocalcemia during magnesium (Mg) depletion has been well described, but the precise mechanism(s) responsible for its occurrence is not yet fully understood. The hypocalcemia has been ascribed to decreased parathyroid hormone (PTH) secretion as well as skeletal resistance to PTH. Whereas the former is well established, controversy exists as to whether or not Mg depletion results in skeletal resistance to PTH. These studies examine the skeletal response to PTH in normal dogs and dogs fed a Mg-free diet for 4-6 mo. Isolated tibia from normal (serum Mg 1.83+/-0.1 mg/100 ml) and experimental dogs (serum Mg 1.34+/-0.15 mg/100 ml) were perfused with Krebs-Henseleit buffer during a constant infusion of 3 ng/ml of synthetic bovine PTH 1-34 (syn b-PTH 1-34). The arteriovenous (A-V) difference for immunoreactive PTH (iPTH) across seven normal bones was 37.5+/-3%. In contrast, the A-V difference for iPTH was markedly depressed to 10.1+/-1% across seven bones from Mg-depleted dogs. These findings correlated well with a biological effect (cyclic AMP [cAMP] production) of syn b-PTH 1-34 on bone. In control bones, cAMP production rose from a basal level of 5.8+/-0.2 to 17.5+/-0.7 pmol/min after syn b-PTH 1-34 infusion. In experimental bones, basal cAMP production was significantly lower than in controls, 4.5+/-0.1 pmol/min, and increased to only 7.1+/-0.4 pmol/min after syn b-PTH 1-34 infusion. Even when PTH concentrations were increased to 20 ng/ml, cAMP production by experimental bones was lower than in control bones perfused with 3 ng/ml. Histological examination of bones from Mg-deficient dogs showed a picture compatible with skeletal inactivity. These studies demonstrate decreased uptake of iPTH and diminished cAMP production by bone, which indicates skeletal resistance to PTH in chronic Mg deficiency.", "contents": "Evidence for skeletal resistance to parathyroid hormone in magnesium deficiency. Studies in isolated perfused bone. Hypocalcemia during magnesium (Mg) depletion has been well described, but the precise mechanism(s) responsible for its occurrence is not yet fully understood. The hypocalcemia has been ascribed to decreased parathyroid hormone (PTH) secretion as well as skeletal resistance to PTH. Whereas the former is well established, controversy exists as to whether or not Mg depletion results in skeletal resistance to PTH. These studies examine the skeletal response to PTH in normal dogs and dogs fed a Mg-free diet for 4-6 mo. Isolated tibia from normal (serum Mg 1.83+/-0.1 mg/100 ml) and experimental dogs (serum Mg 1.34+/-0.15 mg/100 ml) were perfused with Krebs-Henseleit buffer during a constant infusion of 3 ng/ml of synthetic bovine PTH 1-34 (syn b-PTH 1-34). The arteriovenous (A-V) difference for immunoreactive PTH (iPTH) across seven normal bones was 37.5+/-3%. In contrast, the A-V difference for iPTH was markedly depressed to 10.1+/-1% across seven bones from Mg-depleted dogs. These findings correlated well with a biological effect (cyclic AMP [cAMP] production) of syn b-PTH 1-34 on bone. In control bones, cAMP production rose from a basal level of 5.8+/-0.2 to 17.5+/-0.7 pmol/min after syn b-PTH 1-34 infusion. In experimental bones, basal cAMP production was significantly lower than in controls, 4.5+/-0.1 pmol/min, and increased to only 7.1+/-0.4 pmol/min after syn b-PTH 1-34 infusion. Even when PTH concentrations were increased to 20 ng/ml, cAMP production by experimental bones was lower than in control bones perfused with 3 ng/ml. Histological examination of bones from Mg-deficient dogs showed a picture compatible with skeletal inactivity. These studies demonstrate decreased uptake of iPTH and diminished cAMP production by bone, which indicates skeletal resistance to PTH in chronic Mg deficiency."}
{"id": "PMID:227930", "title": "Lipolysis produces changes in the immunoreactivity and cell reactivity of very low density lipoproteins.", "content": "Smaller very low density lipoprotein (VLDL) remnants interact more readily with tissues than do larger \"intact\" VLDL. This may be related to changes in the availability of VLDL apoproteins on the surface of the lipoproteins. To test this hypothesis VLDL were incubated at 37 degrees C with bovine milk lipase (LPL), and the abilities of LPL-treated VLDL preparations to compete with (125)I-low density lipoproteins (LDL) for interaction with cultured normal human fibroblasts were measured. At the same time, the immunologic activities of these preparations were also tested by double antibody radioimmunoassay. Triglyceride (TG) contents of VLDL fell by 30-90% during incubation with LPL and, on zonal ultracentrifugation, VLDL of faster Svedberg unit of flotation (S(f1.063)) rates (>150) were gradually converted to smaller VLDL with lower S(f) rates (21-60). LPL-treated VLDL competed two to five times more effectively with (125)I-LDL for binding to cellular receptors than did control VLDL. Control VLDL incubated with heat-inactivated LPL at 37 degrees C, or with active LPL at 4 degrees C had unaltered cell reactivities and TG contents compared with VLDL incubated without any enzyme. The direct uptake and degradation of LPL-treated VLDL was also assessed by using VLDL (125)I-labeled in apoprotein (Apo)B. LPL-treated VLDL-(125)I-ApoB were taken up and degraded by fibroblast at greater rates than were control VLDL-(125)I-ApoB. Thus, hydrolysis of VLDL lipids was accompanied by an increased ability of VLDL to interact with fibroblasts. The immunoreactivity of ApoB in the same VLDL preparations, expressed as the \"apparent ApoB contents\" of LPL-treated VLDL, increased by 10-50% (P < 0.02) in those assays that contained anti-LDL antisera, but the ApoB of control VLDL remained constant. However, assays that contained antisera directed against ApoB isolated from VLDL did not distinguish between LPL-treated and control VLDL. Thus, VLDL lipid hydrolysis was accompanied by changes in the immunoreactivity of VLDL-ApoB, which probably reflect changes in the disposition of ApoB on the surface of VLDL. The altered disposition of ApoB on VLDL \"remnants\" may be related to their enhanced interaction with cells.", "contents": "Lipolysis produces changes in the immunoreactivity and cell reactivity of very low density lipoproteins. Smaller very low density lipoprotein (VLDL) remnants interact more readily with tissues than do larger \"intact\" VLDL. This may be related to changes in the availability of VLDL apoproteins on the surface of the lipoproteins. To test this hypothesis VLDL were incubated at 37 degrees C with bovine milk lipase (LPL), and the abilities of LPL-treated VLDL preparations to compete with (125)I-low density lipoproteins (LDL) for interaction with cultured normal human fibroblasts were measured. At the same time, the immunologic activities of these preparations were also tested by double antibody radioimmunoassay. Triglyceride (TG) contents of VLDL fell by 30-90% during incubation with LPL and, on zonal ultracentrifugation, VLDL of faster Svedberg unit of flotation (S(f1.063)) rates (>150) were gradually converted to smaller VLDL with lower S(f) rates (21-60). LPL-treated VLDL competed two to five times more effectively with (125)I-LDL for binding to cellular receptors than did control VLDL. Control VLDL incubated with heat-inactivated LPL at 37 degrees C, or with active LPL at 4 degrees C had unaltered cell reactivities and TG contents compared with VLDL incubated without any enzyme. The direct uptake and degradation of LPL-treated VLDL was also assessed by using VLDL (125)I-labeled in apoprotein (Apo)B. LPL-treated VLDL-(125)I-ApoB were taken up and degraded by fibroblast at greater rates than were control VLDL-(125)I-ApoB. Thus, hydrolysis of VLDL lipids was accompanied by an increased ability of VLDL to interact with fibroblasts. The immunoreactivity of ApoB in the same VLDL preparations, expressed as the \"apparent ApoB contents\" of LPL-treated VLDL, increased by 10-50% (P < 0.02) in those assays that contained anti-LDL antisera, but the ApoB of control VLDL remained constant. However, assays that contained antisera directed against ApoB isolated from VLDL did not distinguish between LPL-treated and control VLDL. Thus, VLDL lipid hydrolysis was accompanied by changes in the immunoreactivity of VLDL-ApoB, which probably reflect changes in the disposition of ApoB on the surface of VLDL. The altered disposition of ApoB on VLDL \"remnants\" may be related to their enhanced interaction with cells."}
{"id": "PMID:227931", "title": "Low-density lipoprotein receptor activity in cultured human skin fibroblasts. Mechanism of insulin-induced stimulation.", "content": "Low-density lipoproteins (LDL) receptor activity, as reflected by LDL degradation, was stimulated by the addition of insulin to cultures of human skin fibroblasts. These changes occurred independently of the glucose concentration of the incubation medium and occurred whether or not LDL receptor activity was suppressed. A comparison of the saturation kinetics of LDL receptor activity in the presence and absence of insulin indicated that insulin produced a 35% increase in Vmax with no difference in \"apparent Km\". These results suggest that insulin enhances LDL receptor activity by increasing the number of LDL receptors rather than by influencing binding affinity. In confirmation, LDL degradation by receptor negative cells was not enhanced by insulin. Sterol synthesis from [14C]acetate was also stimulated by insulin, but egress of cholesterol and cellular cholesterol content were unaffected by the hormone. The effect of insulin on LDL receptors was not dependent on its known ability to enhance cellular DNA synthesis and proliferation, because insulin stimulated LDL receptor activity in cells kept quiescent by maintenance in plasma-derived serum that was devoid of platelet derived growth factor. Nevertheless, the effect of insulin in enhancing LDL receptor number, coupled with stimulation of endogenous cholesterol synthesis, provides a mechanism whereby the cell could theoretically increase its supply of cholesterol during times of additional need.", "contents": "Low-density lipoprotein receptor activity in cultured human skin fibroblasts. Mechanism of insulin-induced stimulation. Low-density lipoproteins (LDL) receptor activity, as reflected by LDL degradation, was stimulated by the addition of insulin to cultures of human skin fibroblasts. These changes occurred independently of the glucose concentration of the incubation medium and occurred whether or not LDL receptor activity was suppressed. A comparison of the saturation kinetics of LDL receptor activity in the presence and absence of insulin indicated that insulin produced a 35% increase in Vmax with no difference in \"apparent Km\". These results suggest that insulin enhances LDL receptor activity by increasing the number of LDL receptors rather than by influencing binding affinity. In confirmation, LDL degradation by receptor negative cells was not enhanced by insulin. Sterol synthesis from [14C]acetate was also stimulated by insulin, but egress of cholesterol and cellular cholesterol content were unaffected by the hormone. The effect of insulin on LDL receptors was not dependent on its known ability to enhance cellular DNA synthesis and proliferation, because insulin stimulated LDL receptor activity in cells kept quiescent by maintenance in plasma-derived serum that was devoid of platelet derived growth factor. Nevertheless, the effect of insulin in enhancing LDL receptor number, coupled with stimulation of endogenous cholesterol synthesis, provides a mechanism whereby the cell could theoretically increase its supply of cholesterol during times of additional need."}
{"id": "PMID:227932", "title": "Tubuloglomerular feedback and single nephron function after converting enzyme inhibition in the rat.", "content": "Experiments were done in normal rats to assess kidney, single nephron, and tubuloglomerular feedback responses during renin-angiotensin blockade with the converting enzyme inhibitor (CEI) SQ 20881 (E. R. Squibb & Sons, Princeton, N. Y.) (3 mg/kg, per h). Converting enzyme inhibition was documented by complete blockade of vascular responses to infusions of angiotensin I (600 ng/kg). Control plasma renin activity was 12.5+/-2.7 ng angiotensin I/ml per h (mean+/-SEM) and increased sevenfold with CEI (n = 7). There were parallel increases in glomerular filtration rate from 1.08+/-0.05 to 1.26+/-0.05 ml/min and renal blood flow from 6.7+/-0.4 to 7.5+/-0.5 ml/min. During CEI infusion absolute and fractional sodium excretion were increased 10-fold. Proximal tubule and peritubular capillary pressures were unchanged. Single nephron glomerular filtration rate (SNGFR) was measured from both proximal and distal tubule collections; SNGFR based only on distal collections was significantly increased by CEI. A significant difference was observed between SNGFR values measured from proximal and distal tubule sites (6.0+/-1.6 nl/min) and this difference remained unchanged after CEI administration. Slight decreases in fractional absorption were suggested at micropuncture sites beyond the late proximal tubule, whereas early distal tubule flow rate was augmented by CEI. Tubuloglomerular feedback activity was assessed by measuring changes in proximal tubule stop-flow pressure (SFP) or SNGFR in response to alterations in orthograde microperfusion rate from late proximal tubule sites. During control periods, SFP was decreased 11.2+/-0.4 mm Hg when the perfusion rate was increased to 40 nl/min; during infusion of CEI, the same increase in perfusion rate resulted in a SFP decrement of 6.7+/-0.5 mm Hg (P<.001). When late proximal tubule perfusion rate was increased from 0 to 30 nl/min, SNGFR was decreased by 15.0+/-1.2 nl/min during control conditions, and by 11.3+/-1.3 nl/min during CEI infusion. Attenuation of feedback responsiveness during CEI was also observed at lower perfusion rates with both techniques. These results indicate that blockade of the renin-angiotensin system with CEI reduces the activity of the tubuloglomerular feedback mechanism which may mediate the observed renal vasodilation.", "contents": "Tubuloglomerular feedback and single nephron function after converting enzyme inhibition in the rat. Experiments were done in normal rats to assess kidney, single nephron, and tubuloglomerular feedback responses during renin-angiotensin blockade with the converting enzyme inhibitor (CEI) SQ 20881 (E. R. Squibb & Sons, Princeton, N. Y.) (3 mg/kg, per h). Converting enzyme inhibition was documented by complete blockade of vascular responses to infusions of angiotensin I (600 ng/kg). Control plasma renin activity was 12.5+/-2.7 ng angiotensin I/ml per h (mean+/-SEM) and increased sevenfold with CEI (n = 7). There were parallel increases in glomerular filtration rate from 1.08+/-0.05 to 1.26+/-0.05 ml/min and renal blood flow from 6.7+/-0.4 to 7.5+/-0.5 ml/min. During CEI infusion absolute and fractional sodium excretion were increased 10-fold. Proximal tubule and peritubular capillary pressures were unchanged. Single nephron glomerular filtration rate (SNGFR) was measured from both proximal and distal tubule collections; SNGFR based only on distal collections was significantly increased by CEI. A significant difference was observed between SNGFR values measured from proximal and distal tubule sites (6.0+/-1.6 nl/min) and this difference remained unchanged after CEI administration. Slight decreases in fractional absorption were suggested at micropuncture sites beyond the late proximal tubule, whereas early distal tubule flow rate was augmented by CEI. Tubuloglomerular feedback activity was assessed by measuring changes in proximal tubule stop-flow pressure (SFP) or SNGFR in response to alterations in orthograde microperfusion rate from late proximal tubule sites. During control periods, SFP was decreased 11.2+/-0.4 mm Hg when the perfusion rate was increased to 40 nl/min; during infusion of CEI, the same increase in perfusion rate resulted in a SFP decrement of 6.7+/-0.5 mm Hg (P<.001). When late proximal tubule perfusion rate was increased from 0 to 30 nl/min, SNGFR was decreased by 15.0+/-1.2 nl/min during control conditions, and by 11.3+/-1.3 nl/min during CEI infusion. Attenuation of feedback responsiveness during CEI was also observed at lower perfusion rates with both techniques. These results indicate that blockade of the renin-angiotensin system with CEI reduces the activity of the tubuloglomerular feedback mechanism which may mediate the observed renal vasodilation."}
{"id": "PMID:227933", "title": "Participation of monocyte-macrophages and lymphocytes in the production of a factor that stimulates collagenase and prostaglandin release by rheumatoid synovial cells.", "content": "Cultured mononuclear cells from human peripheral blood produce a soluble factor (MCF) that stimulates collagenase and prostaglandin E2 (PGE2) release by cultured rheumatoid synovial cells up to several hundred fold. These target rheumatoid synovial cells lack conventional macrophage markers. To determine which mononuclear cells are the source of MCF, purified populations of monocyte-macrophages, thymus-derived (T) lymphocytes, and bone marrow-derived (B) lymphocytes were prepared. The monocyte-macrophages alone produced levels of MCF that were proportional to cell density but unaffected by phytohemagglutinin or pokeweed mitogen. No detectable collagenase activity was produced by the cultured monocyte-macrophages or lymphocytes. Purified T lymphocytes produced levels of MCF approximately or equal to 1--3% those of purified monocyte-macrophages in the presence or absence of the above lectins. Purified T lymphocytes modulated the production of MCF by the monocyte-macrophages, however, in a manner dependent upon relative cell densities and the presence of lectins. For example, at optimal ratios of T lymphocytes: monocyte-macrophages, MCF production was markedly stimulated by pokeweed mitogen. Thus, interactions of T lymphocytes and monocyte-macrophages could be important in determining levels of MCF, which regulate collagenase and PGE2 production by target synovial cells in inflammatory arthritis.", "contents": "Participation of monocyte-macrophages and lymphocytes in the production of a factor that stimulates collagenase and prostaglandin release by rheumatoid synovial cells. Cultured mononuclear cells from human peripheral blood produce a soluble factor (MCF) that stimulates collagenase and prostaglandin E2 (PGE2) release by cultured rheumatoid synovial cells up to several hundred fold. These target rheumatoid synovial cells lack conventional macrophage markers. To determine which mononuclear cells are the source of MCF, purified populations of monocyte-macrophages, thymus-derived (T) lymphocytes, and bone marrow-derived (B) lymphocytes were prepared. The monocyte-macrophages alone produced levels of MCF that were proportional to cell density but unaffected by phytohemagglutinin or pokeweed mitogen. No detectable collagenase activity was produced by the cultured monocyte-macrophages or lymphocytes. Purified T lymphocytes produced levels of MCF approximately or equal to 1--3% those of purified monocyte-macrophages in the presence or absence of the above lectins. Purified T lymphocytes modulated the production of MCF by the monocyte-macrophages, however, in a manner dependent upon relative cell densities and the presence of lectins. For example, at optimal ratios of T lymphocytes: monocyte-macrophages, MCF production was markedly stimulated by pokeweed mitogen. Thus, interactions of T lymphocytes and monocyte-macrophages could be important in determining levels of MCF, which regulate collagenase and PGE2 production by target synovial cells in inflammatory arthritis."}
{"id": "PMID:227934", "title": "Physiological and pharmacological influences on thyroxine to 3,5,3'-triiodothyronine conversion and nuclear 3,5,3'-triiodothyronine binding in rat anterior pituitary.", "content": "Our recent in vivo studies have suggested that intrapituitary l-thyroxine (T(4)) to 3,5,3'-triiodo-l-thyronine (T(3)) conversion with subsequent nuclear binding of T(3) is an important pathway by which circulating T(4) can inhibit thyrotropin release. The present studies were performed to evaluate various physiological and pharmacological influences on these two processes in rat anterior pituitary tissue. Intact pituitary fragments were incubated in buffer-1% bovine serum albumin containing 0.14 ng/ml [(131)I]T(3) and 3.8 ng/ml [(125)I]T(4). Nuclei were isolated after 3 h of incubation and the bound iodothyronines identified by paper chromatography. There was 0.3-1% [(125)I]T(3) contaminating the medium [(125)I]T(4), and this did not change during incubation. Nuclear [(125)I]T(4) was not decreased by 650-fold excesses of medium T(3) or T(4), suggesting that it was nonspecifically bound. The ratio of nuclear to medium [(131)I]- and [(125)I]T(3) were expressed as nuclear counts per minute per milligram wet weight of tissue:counts per minute per microliter medium. Intrapituitary T(4) to T(3) conversion was evidenced by the fact that the nuclear:medium (N:M) ratio for [(131)I]T(3) was 0.45+/-0.21, whereas that for [(125)I]T(3) was 2.23+/-1.28 (mean+/-SD, n = 51). A ratio (R), the N:M [(125)I]T(3) divided by the N:M [(131)I]T(3), was used as an index of intrapituitary T(4) to T(3) conversion. Increasing medium T(3) concentrations up to 50 ng/ml caused a progressive decrease in the N:M ratio for both T(3) isotopes, but no change in the value for R, indicating that both competed for the same limited-capacity nuclear receptors. Increasing concentrations of medium T(4) caused no change in the N:M [(131)I]T(3) but did cause a significant decrease in R in three of four experiments. These results suggest saturation of T(4)-5'-monodeiodination occurred at lower T(4) concentrations than saturation of nuclear T(3) binding sites. In hypothyroid rats, the N:M ratios for both [(131)I]T(3) and [(125)I]T(3) were increased (P < 0.005), but R was three-fold higher than in controls (P < 0.005). Animals given 10 mug T(4)/100 g body wt per d for 5 d had significantly decreased N:M ratios for both [(131)I]T(3) and [(125)I]T(3), as well as a decreased value for R. In fasted rats, neither N:M ratio was depressed, although hepatic T(4) to T(3) conversion in the same animals was 50% of control (P < 0.005). Iopanoic acid (13 muM), but not 6-n-propylthiouracil (29 muM), decreased the N:M [(125)I]T(3) with a significant decrease in the value for R (P < 0.025 or less). Neither sodium iodide (6 muM) nor thyrotropin-releasing hormone (7-700 nM) affected the T(3) N:M ratios. These results indicate that intrapituitary T(4) to T(3) conversion is stimulated in hypothyroidism and depressed in T(4)-treated animals, whereas opposite changes occur in hepatic T(4)-5'-monodeiodination. Unlike liver, anterior pituitary T(4)-5'-monodeiodination is not affected by fasting or incubation with 6-n-propyl-2-thiouracil, but T(4) to T(3) conversion is inhibited in both by iopanoic acid. These results indicate that there are important differences between anterior pituitary and other tissues in the regulation of T(4)-5'-monodeiodination.", "contents": "Physiological and pharmacological influences on thyroxine to 3,5,3'-triiodothyronine conversion and nuclear 3,5,3'-triiodothyronine binding in rat anterior pituitary. Our recent in vivo studies have suggested that intrapituitary l-thyroxine (T(4)) to 3,5,3'-triiodo-l-thyronine (T(3)) conversion with subsequent nuclear binding of T(3) is an important pathway by which circulating T(4) can inhibit thyrotropin release. The present studies were performed to evaluate various physiological and pharmacological influences on these two processes in rat anterior pituitary tissue. Intact pituitary fragments were incubated in buffer-1% bovine serum albumin containing 0.14 ng/ml [(131)I]T(3) and 3.8 ng/ml [(125)I]T(4). Nuclei were isolated after 3 h of incubation and the bound iodothyronines identified by paper chromatography. There was 0.3-1% [(125)I]T(3) contaminating the medium [(125)I]T(4), and this did not change during incubation. Nuclear [(125)I]T(4) was not decreased by 650-fold excesses of medium T(3) or T(4), suggesting that it was nonspecifically bound. The ratio of nuclear to medium [(131)I]- and [(125)I]T(3) were expressed as nuclear counts per minute per milligram wet weight of tissue:counts per minute per microliter medium. Intrapituitary T(4) to T(3) conversion was evidenced by the fact that the nuclear:medium (N:M) ratio for [(131)I]T(3) was 0.45+/-0.21, whereas that for [(125)I]T(3) was 2.23+/-1.28 (mean+/-SD, n = 51). A ratio (R), the N:M [(125)I]T(3) divided by the N:M [(131)I]T(3), was used as an index of intrapituitary T(4) to T(3) conversion. Increasing medium T(3) concentrations up to 50 ng/ml caused a progressive decrease in the N:M ratio for both T(3) isotopes, but no change in the value for R, indicating that both competed for the same limited-capacity nuclear receptors. Increasing concentrations of medium T(4) caused no change in the N:M [(131)I]T(3) but did cause a significant decrease in R in three of four experiments. These results suggest saturation of T(4)-5'-monodeiodination occurred at lower T(4) concentrations than saturation of nuclear T(3) binding sites. In hypothyroid rats, the N:M ratios for both [(131)I]T(3) and [(125)I]T(3) were increased (P < 0.005), but R was three-fold higher than in controls (P < 0.005). Animals given 10 mug T(4)/100 g body wt per d for 5 d had significantly decreased N:M ratios for both [(131)I]T(3) and [(125)I]T(3), as well as a decreased value for R. In fasted rats, neither N:M ratio was depressed, although hepatic T(4) to T(3) conversion in the same animals was 50% of control (P < 0.005). Iopanoic acid (13 muM), but not 6-n-propylthiouracil (29 muM), decreased the N:M [(125)I]T(3) with a significant decrease in the value for R (P < 0.025 or less). Neither sodium iodide (6 muM) nor thyrotropin-releasing hormone (7-700 nM) affected the T(3) N:M ratios. These results indicate that intrapituitary T(4) to T(3) conversion is stimulated in hypothyroidism and depressed in T(4)-treated animals, whereas opposite changes occur in hepatic T(4)-5'-monodeiodination. Unlike liver, anterior pituitary T(4)-5'-monodeiodination is not affected by fasting or incubation with 6-n-propyl-2-thiouracil, but T(4) to T(3) conversion is inhibited in both by iopanoic acid. These results indicate that there are important differences between anterior pituitary and other tissues in the regulation of T(4)-5'-monodeiodination."}
{"id": "PMID:227935", "title": "Beta adrenergic and muscarinic cholinergic receptors in canine myocardium. Effects of ischemia.", "content": "Experimental myocardial ischemia produced in dogs by proximal left anterior descending coronary artery ligation is accompanied by relatively rapid (1 h) increases in the number of (-) [3H]dihydroalprenolol binding sites without changing their dissociation constants in ischemic left ventricular tissue. The changes, persist for at least 8 h and are accompanied by marked decreases in myocardial tissue ischemic region norepinephrine content. In contrast, in the same canine model 1 h of proximal left anterior descending coronary artery ligation did not result in a significant change in the number of [3H]quinuclidynl benzilate binding sites of their dissociation constants. However, the number of [3H]quinuclidynl benzilate binding sites (muscarinic cholinergic receptors) are 50--70% greater than (-) [3H]dihydroalprenolol binding sites (beta adrenergic receptors) in canine left ventricular tissue. Thus, the data suggest that proximal left anterior descending coronary artery occlusion for 1 h significantly increases the number of beta adrenergic receptors in ischemic left ventricular tissue without changing the number of muscarinic cholinergic receptors. Whether the ischemia-produced increase in cardiac beta-receptor content is causally related to increased cyclic AMP levels that develop in ischemic tissue and/or an etiologic factor in arrhythmias originating from ischemic myocardial tissue will have to be determined in additional studies.", "contents": "Beta adrenergic and muscarinic cholinergic receptors in canine myocardium. Effects of ischemia. Experimental myocardial ischemia produced in dogs by proximal left anterior descending coronary artery ligation is accompanied by relatively rapid (1 h) increases in the number of (-) [3H]dihydroalprenolol binding sites without changing their dissociation constants in ischemic left ventricular tissue. The changes, persist for at least 8 h and are accompanied by marked decreases in myocardial tissue ischemic region norepinephrine content. In contrast, in the same canine model 1 h of proximal left anterior descending coronary artery ligation did not result in a significant change in the number of [3H]quinuclidynl benzilate binding sites of their dissociation constants. However, the number of [3H]quinuclidynl benzilate binding sites (muscarinic cholinergic receptors) are 50--70% greater than (-) [3H]dihydroalprenolol binding sites (beta adrenergic receptors) in canine left ventricular tissue. Thus, the data suggest that proximal left anterior descending coronary artery occlusion for 1 h significantly increases the number of beta adrenergic receptors in ischemic left ventricular tissue without changing the number of muscarinic cholinergic receptors. Whether the ischemia-produced increase in cardiac beta-receptor content is causally related to increased cyclic AMP levels that develop in ischemic tissue and/or an etiologic factor in arrhythmias originating from ischemic myocardial tissue will have to be determined in additional studies."}
{"id": "PMID:227936", "title": "New function for high density lipoproteins. Their participation in intravascular reactions of bacterial lipopolysaccharides.", "content": "The addition of bacterial lipopolysaccharide (LPS) from Escherichia coli 0111:B4 or Salmonella minnesota R595 to plasma (or serum) resulted in a marked reduction of the hydrated buoyant density of the parent LPS (0111:B4 [d = 1.44 g/cm3] and R595 [d = 1.38 g/cm3]), to d less than 1.2 g/cm3. This reduction in buoyant density to less than 1.2 g/cm3 of the LPS required plasma (or serum) lipid. Delipidation of plasma (or serum) by extraction with n-butanol/diisopropyl ether (40/60, vol:vol) prevented the conversion of the parent LPS to a form with d less than 1.2 g/cm3. Reversal of the effect of delipidation was accomplished by the addition of physiologic concentrations of high density lipoprotein (HDL). In contrast, as much as two times normal serum concentration of low density or very low density lipoprotein were ineffective. The ability of normal plasma (or serum) to inhibit the pyrogenic activity of LPS, lost after delipidation, was also restored after the addition of HDL. Preliminary results suggested that prior modifications of the LPS, probably disaggregation, may be required before interaction with HDL.", "contents": "New function for high density lipoproteins. Their participation in intravascular reactions of bacterial lipopolysaccharides. The addition of bacterial lipopolysaccharide (LPS) from Escherichia coli 0111:B4 or Salmonella minnesota R595 to plasma (or serum) resulted in a marked reduction of the hydrated buoyant density of the parent LPS (0111:B4 [d = 1.44 g/cm3] and R595 [d = 1.38 g/cm3]), to d less than 1.2 g/cm3. This reduction in buoyant density to less than 1.2 g/cm3 of the LPS required plasma (or serum) lipid. Delipidation of plasma (or serum) by extraction with n-butanol/diisopropyl ether (40/60, vol:vol) prevented the conversion of the parent LPS to a form with d less than 1.2 g/cm3. Reversal of the effect of delipidation was accomplished by the addition of physiologic concentrations of high density lipoprotein (HDL). In contrast, as much as two times normal serum concentration of low density or very low density lipoprotein were ineffective. The ability of normal plasma (or serum) to inhibit the pyrogenic activity of LPS, lost after delipidation, was also restored after the addition of HDL. Preliminary results suggested that prior modifications of the LPS, probably disaggregation, may be required before interaction with HDL."}
{"id": "PMID:227937", "title": "Studies of relationship among bile flow, liver plasma membrane NaK-ATPase, and membrane microviscosity in the rat.", "content": "Liver plasma membrane (LPM) NaK-ATPase activity, LPM fluidity, and bile acid-independent flow (BAIF) were studied in rats pretreated with one of five experimental agents. Compared with controls, BAIF was increased 24.6% by thyroid hormone and 34.4% by phenobarbital, decreased by ethinyl estradiol, but unchanged by propylene glycol and cortisone acetate. Parallel to the observed changes in BAIF, NaK-ATPase activity also was increased by thyroid hormone (40.8%) and decreased by ethinyl estradiol (26.2%). In contrast, NaK-ATPase activity failed to increase after phenobarbital but did increase 36% after propylene glycol and 34.8% after cortisone acetate. Thus BAIF and NaK-ATPase activity did not always change in parallel. The NaK-ATPase K(m) for ATP was not affected by any of these agents.LPM fluidity, measured by fluorescence polarization using the probe 1,6-diphenyl-1,3,5-hexatriene, was found to be increased by propylene glycol, thyroid hormone, and cortisone acetate, decreased by ethinyl estradiol, and unaffected by phenobarbital. Thus in these cases, induced changes in LPM fluidity paralleled those in NaK-ATPase activity. In no case did Mg-ATPase or 5'-nucleotidase activities change in the same direction as NaK-ATPase, and the activity of neither of these enzymes correlated with LPM fluidity, thus indicating the selective nature of the changes in LPM enzyme activity caused by the agents. These findings indicate that LPM fluidity correlates with NaK-ATPase activity and may influence the activity of this enzyme. However, the nature of the role of LPM NaK-ATPase in bile secretion is uncertain and needs further study.", "contents": "Studies of relationship among bile flow, liver plasma membrane NaK-ATPase, and membrane microviscosity in the rat. Liver plasma membrane (LPM) NaK-ATPase activity, LPM fluidity, and bile acid-independent flow (BAIF) were studied in rats pretreated with one of five experimental agents. Compared with controls, BAIF was increased 24.6% by thyroid hormone and 34.4% by phenobarbital, decreased by ethinyl estradiol, but unchanged by propylene glycol and cortisone acetate. Parallel to the observed changes in BAIF, NaK-ATPase activity also was increased by thyroid hormone (40.8%) and decreased by ethinyl estradiol (26.2%). In contrast, NaK-ATPase activity failed to increase after phenobarbital but did increase 36% after propylene glycol and 34.8% after cortisone acetate. Thus BAIF and NaK-ATPase activity did not always change in parallel. The NaK-ATPase K(m) for ATP was not affected by any of these agents.LPM fluidity, measured by fluorescence polarization using the probe 1,6-diphenyl-1,3,5-hexatriene, was found to be increased by propylene glycol, thyroid hormone, and cortisone acetate, decreased by ethinyl estradiol, and unaffected by phenobarbital. Thus in these cases, induced changes in LPM fluidity paralleled those in NaK-ATPase activity. In no case did Mg-ATPase or 5'-nucleotidase activities change in the same direction as NaK-ATPase, and the activity of neither of these enzymes correlated with LPM fluidity, thus indicating the selective nature of the changes in LPM enzyme activity caused by the agents. These findings indicate that LPM fluidity correlates with NaK-ATPase activity and may influence the activity of this enzyme. However, the nature of the role of LPM NaK-ATPase in bile secretion is uncertain and needs further study."}
{"id": "PMID:227938", "title": "Appearance and characterization of lipoprotein X during continuous intralipid infusions in the neonate.", "content": "The development of hyperphospholipidemia and hypercholesterolemia was studied in infants that required total parenteral nutrition and given a continuous infusion of Intralipid, (1-4 g/kg body wt per 24 h. Detailed studies were carried out on infusion periods lasting 1-10 d. After 24 h there was a marked increase in plasma free cholesterol (68%) and phospholipid (77%) concentrations. Based on the amount of cholesterol in Intralipid, and the rate of infusion, it was estimated that at least 50% of the plasma cholesterol increment during 64-h infusions was derived from endogenous sources. By contrast, the hyperphospholipidemia could be attributed to the Intralipid as the rise in plasma was calculated to be equivalent to only 16% of the exogenous phospholipid infused. Approximately 10% of the phospholipid in Intralipid was in a triglyceride-free mesophase form with a free cholesterol:phospholipid molar ratio of 0.063. There were no systematic changes in plasma concentrations of cholesterol ester or triglyceride during Intralipid infusions. The increase in free cholesterol and phospholipid was localized in the low density lipoproteins (d = 1.006-1.063 g/ml). The presence of lipoprotein X (Lp-X) in the low density lipoprotein fraction was demonstrated by electrophoresis in agar and by isolation and chemical characterization with hydroxylapatite chromatography. Isoelectric focusing of urea-soluble protein of Lp-X revealed that albumin and apolipoproteins CII and CIII were major components, whereas apolipoprotein E and AI were minor constituents. The abnormal lipoprotein was apparent by 16 h during 64 h of infusion. After 6 d of continuous infusions the free cholesterol in Lp-X was 30+/-10 mg/dl (mean+/-SD), which represents a total Lp-X mass of 90 mg/dl. After cessation of the infusion, Lp-X, as monitored by electrophoresis in agar, disappeared within 72-96 h. Thus, during infusion of Intralipid in infants at rates commonly employed, the capacity of the clearance mechanisms for phospholipid are exceeded, which causes the accumulation of phospholipid and free cholesterol in the form of Lp-X particles. It is suggested that mesophase phospholipids in Intralipid may play a significant role in this process.", "contents": "Appearance and characterization of lipoprotein X during continuous intralipid infusions in the neonate. The development of hyperphospholipidemia and hypercholesterolemia was studied in infants that required total parenteral nutrition and given a continuous infusion of Intralipid, (1-4 g/kg body wt per 24 h. Detailed studies were carried out on infusion periods lasting 1-10 d. After 24 h there was a marked increase in plasma free cholesterol (68%) and phospholipid (77%) concentrations. Based on the amount of cholesterol in Intralipid, and the rate of infusion, it was estimated that at least 50% of the plasma cholesterol increment during 64-h infusions was derived from endogenous sources. By contrast, the hyperphospholipidemia could be attributed to the Intralipid as the rise in plasma was calculated to be equivalent to only 16% of the exogenous phospholipid infused. Approximately 10% of the phospholipid in Intralipid was in a triglyceride-free mesophase form with a free cholesterol:phospholipid molar ratio of 0.063. There were no systematic changes in plasma concentrations of cholesterol ester or triglyceride during Intralipid infusions. The increase in free cholesterol and phospholipid was localized in the low density lipoproteins (d = 1.006-1.063 g/ml). The presence of lipoprotein X (Lp-X) in the low density lipoprotein fraction was demonstrated by electrophoresis in agar and by isolation and chemical characterization with hydroxylapatite chromatography. Isoelectric focusing of urea-soluble protein of Lp-X revealed that albumin and apolipoproteins CII and CIII were major components, whereas apolipoprotein E and AI were minor constituents. The abnormal lipoprotein was apparent by 16 h during 64 h of infusion. After 6 d of continuous infusions the free cholesterol in Lp-X was 30+/-10 mg/dl (mean+/-SD), which represents a total Lp-X mass of 90 mg/dl. After cessation of the infusion, Lp-X, as monitored by electrophoresis in agar, disappeared within 72-96 h. Thus, during infusion of Intralipid in infants at rates commonly employed, the capacity of the clearance mechanisms for phospholipid are exceeded, which causes the accumulation of phospholipid and free cholesterol in the form of Lp-X particles. It is suggested that mesophase phospholipids in Intralipid may play a significant role in this process."}
{"id": "PMID:227939", "title": "Hydroxyl radical generation by polymorphonuclear leukocytes measured by electron spin resonance spectroscopy.", "content": "Electron spin resonance spectroscopy using the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) was employed to detect the formation of hydroxyl radicals (OH.) by phagocytosing polymorphonuclear leukocytes (PMN). An electron spin resonance signal with the identical g value and splitting characteristics of the DMPO/OH). adduct was detected on incubation of normal PMN with opsonized zymosan. Adduct formation was strongly inhibited by superoxide dismutase and by the OH. scavenger mannitol, but catalase had little or no effect. (DMPO/OH). was not formed by PMN from a patient with chronic granulomatous disease; in contrast, adduct formation by PMN which lack myeloperoxidase was greater than normal. These findings are discussed in relation to the formation of OH. by PMN.", "contents": "Hydroxyl radical generation by polymorphonuclear leukocytes measured by electron spin resonance spectroscopy. Electron spin resonance spectroscopy using the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) was employed to detect the formation of hydroxyl radicals (OH.) by phagocytosing polymorphonuclear leukocytes (PMN). An electron spin resonance signal with the identical g value and splitting characteristics of the DMPO/OH). adduct was detected on incubation of normal PMN with opsonized zymosan. Adduct formation was strongly inhibited by superoxide dismutase and by the OH. scavenger mannitol, but catalase had little or no effect. (DMPO/OH). was not formed by PMN from a patient with chronic granulomatous disease; in contrast, adduct formation by PMN which lack myeloperoxidase was greater than normal. These findings are discussed in relation to the formation of OH. by PMN."}
{"id": "PMID:227941", "title": "Comparison of electron microscopy, enzyme-linked immunosorbent assay, solid-phase radioimmunoassay, and indirect immunofluorescence for detection of human rotavirus antigen in faeces.", "content": "Four techniques were compared for their practicability, speed, and sensitivity for the detection of human rotavirus. Radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) were found to be the most sensitive means of identifying rotavirus, and, once processed, up to 40 specimens could be examined daily. Electron microscopy, although less sensitive than these techniques, had the advantage of being able to detect other viral agents present in faecal extracts. Indirect immunofluorescence failed to detect rotavirus as often as the other three methods. In laboratories where routine examination of faecal specimens from patients with gastroenteritis is required, ELISA and RIA are useful alternatives to electron microscopy.", "contents": "Comparison of electron microscopy, enzyme-linked immunosorbent assay, solid-phase radioimmunoassay, and indirect immunofluorescence for detection of human rotavirus antigen in faeces. Four techniques were compared for their practicability, speed, and sensitivity for the detection of human rotavirus. Radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) were found to be the most sensitive means of identifying rotavirus, and, once processed, up to 40 specimens could be examined daily. Electron microscopy, although less sensitive than these techniques, had the advantage of being able to detect other viral agents present in faecal extracts. Indirect immunofluorescence failed to detect rotavirus as often as the other three methods. In laboratories where routine examination of faecal specimens from patients with gastroenteritis is required, ELISA and RIA are useful alternatives to electron microscopy."}
{"id": "PMID:227942", "title": "Alpha-1-antitrypsin Pi S phenotype and liver cell inclusion bodies in alcoholic hepatitis.", "content": "Typical liver cell inclusions of alpha-1-antitrypsin deficiency were found in a patient with the Pi S phenotype and acute alcoholic hepatitis. It is suggested that the inclusions resulted from the combined effects of the S phenotype and alcohol and, on the basis of the known chemistry of the variant antitrypsins, that the lowered serum concentration of antitrypsin associated with the S allele may be due to hepatic holdup.", "contents": "Alpha-1-antitrypsin Pi S phenotype and liver cell inclusion bodies in alcoholic hepatitis. Typical liver cell inclusions of alpha-1-antitrypsin deficiency were found in a patient with the Pi S phenotype and acute alcoholic hepatitis. It is suggested that the inclusions resulted from the combined effects of the S phenotype and alcohol and, on the basis of the known chemistry of the variant antitrypsins, that the lowered serum concentration of antitrypsin associated with the S allele may be due to hepatic holdup."}
{"id": "PMID:227943", "title": "A radioimmunoassay for hepatitis A antigen and antibody.", "content": "The HAVAB radioimmunoassay for the detection of antibody to hepatitis A is assessed. Its modification to detect virus in faecal samples is described and in this it was found to be more sensitive and specific than electron microscopy.", "contents": "A radioimmunoassay for hepatitis A antigen and antibody. The HAVAB radioimmunoassay for the detection of antibody to hepatitis A is assessed. Its modification to detect virus in faecal samples is described and in this it was found to be more sensitive and specific than electron microscopy."}
{"id": "PMID:227944", "title": "Toxic effects of metals from the environment on hair growth and structure.", "content": "Diffuse alopecia related to ingestion of toxic metals from the environment has been observed in 36 patients. Copper, arsenic, mercury and cadmium were involved and the intensity of disturbance of the hair cycle, heralded by presence of dystrophic hairs, was proportional to the amount of toxic material detected in blood and urine. Toxicity can be observed in vitro by measuring labeled cells on squash preparations after incorporation of tritiated uridine and thymidine in plucked hairs. The labeling indexes, as well as the ratio between cells entering the S phase and the viable cells were always lower in toxic alopecia than in normal hair. Toxic metals do not seem to affect the morphology of the hair shaft.", "contents": "Toxic effects of metals from the environment on hair growth and structure. Diffuse alopecia related to ingestion of toxic metals from the environment has been observed in 36 patients. Copper, arsenic, mercury and cadmium were involved and the intensity of disturbance of the hair cycle, heralded by presence of dystrophic hairs, was proportional to the amount of toxic material detected in blood and urine. Toxicity can be observed in vitro by measuring labeled cells on squash preparations after incorporation of tritiated uridine and thymidine in plucked hairs. The labeling indexes, as well as the ratio between cells entering the S phase and the viable cells were always lower in toxic alopecia than in normal hair. Toxic metals do not seem to affect the morphology of the hair shaft."}
{"id": "PMID:227945", "title": "Mechanisms involved in alpha-adrenergic effects of catecholamines on liver metabolism.", "content": "Recent results have indicated that alpha-adrenergic receptors are the major mediators of catecholamine actions on liver metabolism in several species. It is well-established that cAMP and cAMP-dependent protein kinase are not involved in hepatic alpha-adrenergic effects. This review presents evidence that alpha-adrenergic stimulation of glycogenolysis in rat liver involves the mobilization of Ca2+ ions from mitochondria and stimulation of phosphorylase kinase by the resulting increase in cytosolic Ca2+ concentration. Possible mechanisms by which activation of alpha-adrenergic receptors causes release of mitochondrial Ca2+ and affects other cell processes are discussed.", "contents": "Mechanisms involved in alpha-adrenergic effects of catecholamines on liver metabolism. Recent results have indicated that alpha-adrenergic receptors are the major mediators of catecholamine actions on liver metabolism in several species. It is well-established that cAMP and cAMP-dependent protein kinase are not involved in hepatic alpha-adrenergic effects. This review presents evidence that alpha-adrenergic stimulation of glycogenolysis in rat liver involves the mobilization of Ca2+ ions from mitochondria and stimulation of phosphorylase kinase by the resulting increase in cytosolic Ca2+ concentration. Possible mechanisms by which activation of alpha-adrenergic receptors causes release of mitochondrial Ca2+ and affects other cell processes are discussed."}
{"id": "PMID:227946", "title": "Inhibition of lipolysis in hamster adipocytes by the cation ionophor X537A.", "content": "The present study reports the effects of the lipophylic ionophore X537A on lipolysis and accumulation of cAMP in isolated hamster epidiymal adipocytes. X537A inhibited lipolysis activated with norepinephrine, isoproterenol, dibutyryl cAMP or theophylline but failed to influence basal lipolysis. The minimum effective concentration of X537A required to inhibit lipolysis was between 1 and 3 micrograms/ml; at a concentration of 10 micrograms/ml, X537A inhibited lipolysis by approximately 50%. The antilipolytic effect of X537A does not result from decreased formation of cAMP because the accumulation of cAMP in response to isoproterenol or theophylline was significantly potentiated in the presence of the ionophore. Most of the additional cAMP that accumulated in the presence of X537A was found to be intracellelular, the distribution of cAMP between cells and incubation medium not being influenced by X537A. Neither the basal activity of cAMP dependent protein kinase nor the activity in the presence of isoproterenol or theophylline was influenced by X537A. The effects of X537A on lipolysis and on accumulation of cAMP were found to persist in the absence of extracellular calcium, but adipocytes that were preincubated in a calcium free media containing 4.0 mM EGTA failed to respond to X537A with an increase in cAMP levels. It is concluded that X537A inhibits lipolysis by uncoupling cAMP accumulation from activation of triglyceride lipase by a mechanism unrelated to activation of protein kinase.", "contents": "Inhibition of lipolysis in hamster adipocytes by the cation ionophor X537A. The present study reports the effects of the lipophylic ionophore X537A on lipolysis and accumulation of cAMP in isolated hamster epidiymal adipocytes. X537A inhibited lipolysis activated with norepinephrine, isoproterenol, dibutyryl cAMP or theophylline but failed to influence basal lipolysis. The minimum effective concentration of X537A required to inhibit lipolysis was between 1 and 3 micrograms/ml; at a concentration of 10 micrograms/ml, X537A inhibited lipolysis by approximately 50%. The antilipolytic effect of X537A does not result from decreased formation of cAMP because the accumulation of cAMP in response to isoproterenol or theophylline was significantly potentiated in the presence of the ionophore. Most of the additional cAMP that accumulated in the presence of X537A was found to be intracellelular, the distribution of cAMP between cells and incubation medium not being influenced by X537A. Neither the basal activity of cAMP dependent protein kinase nor the activity in the presence of isoproterenol or theophylline was influenced by X537A. The effects of X537A on lipolysis and on accumulation of cAMP were found to persist in the absence of extracellular calcium, but adipocytes that were preincubated in a calcium free media containing 4.0 mM EGTA failed to respond to X537A with an increase in cAMP levels. It is concluded that X537A inhibits lipolysis by uncoupling cAMP accumulation from activation of triglyceride lipase by a mechanism unrelated to activation of protein kinase."}
{"id": "PMID:227947", "title": "Human gingival lymphocytes. I. Methodology for the isolation of human gingival lymphocytes.", "content": "Various methodologies were examined for the isolation of inflammatory cells from diseased human gingiva. The best recovery of viable gingival lymphocytes (gMNC) was achieved by a method which combined initial collagenase digestion followed by gentle teasing with an 18-gauge needle.", "contents": "Human gingival lymphocytes. I. Methodology for the isolation of human gingival lymphocytes. Various methodologies were examined for the isolation of inflammatory cells from diseased human gingiva. The best recovery of viable gingival lymphocytes (gMNC) was achieved by a method which combined initial collagenase digestion followed by gentle teasing with an 18-gauge needle."}
{"id": "PMID:227948", "title": "Lack of effect of fluoride on urinary cAMP excretion in rats.", "content": "The urinary excretion of cyclic 3'5'-adenosine monophosphate (cAMP) was measured in rats provided a low fluoride diet (less than 0.5 ppm) and drinking water containing either 0 or 25 ppm of fluoride. The pMole cAMP/microgram creatinine ratio decreased with age but was not influenced by fluoride intake.", "contents": "Lack of effect of fluoride on urinary cAMP excretion in rats. The urinary excretion of cyclic 3'5'-adenosine monophosphate (cAMP) was measured in rats provided a low fluoride diet (less than 0.5 ppm) and drinking water containing either 0 or 25 ppm of fluoride. The pMole cAMP/microgram creatinine ratio decreased with age but was not influenced by fluoride intake."}
{"id": "PMID:227949", "title": "Granular-cell tumors of the vulva: a report of three cases.", "content": "Three black women were found to have granular-cell tumors on the vulva; in one, there were several additionally in other cutaneous sites. Although this benign neoplasm is uncommon on the vulva, it should be considered in the differential diagnosis of nodular lesions on the vulva. Granular-cell tumors in multiplicity occur frequently and are not a sign of metastatic disease. This lesion has predilection for blacks. Pseudocarcinomatous hyperplasia occurs typically in overlying squamous epithelium and may be misinterpreted as squamous-cell carcinoma.", "contents": "Granular-cell tumors of the vulva: a report of three cases. Three black women were found to have granular-cell tumors on the vulva; in one, there were several additionally in other cutaneous sites. Although this benign neoplasm is uncommon on the vulva, it should be considered in the differential diagnosis of nodular lesions on the vulva. Granular-cell tumors in multiplicity occur frequently and are not a sign of metastatic disease. This lesion has predilection for blacks. Pseudocarcinomatous hyperplasia occurs typically in overlying squamous epithelium and may be misinterpreted as squamous-cell carcinoma."}
{"id": "PMID:227957", "title": "Antibody-independent neutralization of vesicular stomatitis virus by human complement. II. Formation of VSV-lipoprotein complexes in human serum and complement-dependent viral lysis.", "content": "Vesicular stomatitis virus (VSV) is efficiently neutralized by normal, nonimmune human serum without the participation of antibody. Neutralization is complement- (C) dependent and requires the early-acting components of the classical pathway, C1, C4, C2, and C3, but not later-acting C components. In further studies, normal human serum was found to markedly increase the density of a variable but significant proportion of virus-associated RNA and to markedly decrease the density of the remainder of virus-associated RNA. The RNA of increased density was found to be dense ribonucleocapsid cores released from VSV by C-dependent viral lysis mediated through the classical pathway. The released ribonucleocapsid cores found at the bottom of sucrose density gradient after incubation of VSV with human serum were resistant to degradation by proteolytic enzymes. The VSV-derived RNA found floating on the tops of sucrose density gradients performed on serum-treated VSV was infectious virus. The decreased density was due to binding of VSV to human serum lipoproteins (LP), primarily very low density lipoproteins (VLDL). Binding of VLDL to VSV required the presence of the viral envelope and the external glycoprotein, G. Despite the binding of LP to VSV, LP did not neutralize VSV, and LP-depleted sera were fully active in neutralizing VSV. Thus, LP do not represent an accessory factor for the C-dependent neutralization of VSV.", "contents": "Antibody-independent neutralization of vesicular stomatitis virus by human complement. II. Formation of VSV-lipoprotein complexes in human serum and complement-dependent viral lysis. Vesicular stomatitis virus (VSV) is efficiently neutralized by normal, nonimmune human serum without the participation of antibody. Neutralization is complement- (C) dependent and requires the early-acting components of the classical pathway, C1, C4, C2, and C3, but not later-acting C components. In further studies, normal human serum was found to markedly increase the density of a variable but significant proportion of virus-associated RNA and to markedly decrease the density of the remainder of virus-associated RNA. The RNA of increased density was found to be dense ribonucleocapsid cores released from VSV by C-dependent viral lysis mediated through the classical pathway. The released ribonucleocapsid cores found at the bottom of sucrose density gradient after incubation of VSV with human serum were resistant to degradation by proteolytic enzymes. The VSV-derived RNA found floating on the tops of sucrose density gradients performed on serum-treated VSV was infectious virus. The decreased density was due to binding of VSV to human serum lipoproteins (LP), primarily very low density lipoproteins (VLDL). Binding of VLDL to VSV required the presence of the viral envelope and the external glycoprotein, G. Despite the binding of LP to VSV, LP did not neutralize VSV, and LP-depleted sera were fully active in neutralizing VSV. Thus, LP do not represent an accessory factor for the C-dependent neutralization of VSV."}
{"id": "PMID:227959", "title": "Target-effector interaction in the natural killer cell system. IV. Modulation by cyclic nucleotides.", "content": "Dibutyryl cAMP (dB-cAMP) and the cAMP elevating agents, prostaglandin E1, theophylline, and histamine markedly suppressed NK cytolytic function in a dose- and rate-dependent manner. The inhibition was rapidly induced and persisted in the presence of the drugs. Separate pretreatment of targets and highly purified NK cells, isolated by a target binding and velocity sedimentation technique, revealed that PGE1 and dB-cAMP acted at the level of the effector cell in a short-term cytolytic assay. In contrast to the inhibitory effects of cAMP elevating agents, dB-cGMP and carbamylcholine caused a small but significant acceleration in the rate of lysis and could compete with inhibitory doses of dB-cAMP to reduce the level of suppression thereby suggesting that the cAMP-cGMP ratio might be important in NK-mediated lysis. Insulin had no effect on NK activity, whereas T cell-mediated cytolysis was augmented by insulin and cGMP if the effector cells were taken early after alloimmunization but not later. Neither cAMP- nor cGMP-elevating agents affected the frequency of NK-target cell conjugates. These results are compatible with the hypothesis that cyclic nucleotides may be involved in triggering the lytic event within NK cells.", "contents": "Target-effector interaction in the natural killer cell system. IV. Modulation by cyclic nucleotides. Dibutyryl cAMP (dB-cAMP) and the cAMP elevating agents, prostaglandin E1, theophylline, and histamine markedly suppressed NK cytolytic function in a dose- and rate-dependent manner. The inhibition was rapidly induced and persisted in the presence of the drugs. Separate pretreatment of targets and highly purified NK cells, isolated by a target binding and velocity sedimentation technique, revealed that PGE1 and dB-cAMP acted at the level of the effector cell in a short-term cytolytic assay. In contrast to the inhibitory effects of cAMP elevating agents, dB-cGMP and carbamylcholine caused a small but significant acceleration in the rate of lysis and could compete with inhibitory doses of dB-cAMP to reduce the level of suppression thereby suggesting that the cAMP-cGMP ratio might be important in NK-mediated lysis. Insulin had no effect on NK activity, whereas T cell-mediated cytolysis was augmented by insulin and cGMP if the effector cells were taken early after alloimmunization but not later. Neither cAMP- nor cGMP-elevating agents affected the frequency of NK-target cell conjugates. These results are compatible with the hypothesis that cyclic nucleotides may be involved in triggering the lytic event within NK cells."}
{"id": "PMID:227960", "title": "Production of human lymphocyte mediators after activation with periodate or neuraminidase and galactose oxidase.", "content": "Treatment of human mononuclear cells with sodium metaperiodate (NaIO4) or neuraminidase and galactose oxidase (NGO) results in lymphocyte activation and subsequent generation of supernatants rich in migration inhibitory factor (MIF) and leukocyte inhibitory factor (LIF). Preliminary characterization of these mediators by Sephadex G-100 gel filtration suggests that they are similar to antigen- and concanavalin A-induced MIF and LIF, eluting in the 25000 m.w. and 68000 m.w. regions, respectively. The possibility of galactose oxidase carryover into the supernatants has been studied and conditions are described that minimize this eventuality. A method is presented for producing control and lymphokine-rich supernatants both of which have been exposed to identical concentrations of NGO although in the control activation is blocked by the addition of 0.1 M galactose to the incubation. These findings establish NaIO4 and NGO as useful mitogens for generating human lymphokine-rich supernatants that can be used without further purification.", "contents": "Production of human lymphocyte mediators after activation with periodate or neuraminidase and galactose oxidase. Treatment of human mononuclear cells with sodium metaperiodate (NaIO4) or neuraminidase and galactose oxidase (NGO) results in lymphocyte activation and subsequent generation of supernatants rich in migration inhibitory factor (MIF) and leukocyte inhibitory factor (LIF). Preliminary characterization of these mediators by Sephadex G-100 gel filtration suggests that they are similar to antigen- and concanavalin A-induced MIF and LIF, eluting in the 25000 m.w. and 68000 m.w. regions, respectively. The possibility of galactose oxidase carryover into the supernatants has been studied and conditions are described that minimize this eventuality. A method is presented for producing control and lymphokine-rich supernatants both of which have been exposed to identical concentrations of NGO although in the control activation is blocked by the addition of 0.1 M galactose to the incubation. These findings establish NaIO4 and NGO as useful mitogens for generating human lymphokine-rich supernatants that can be used without further purification."}
{"id": "PMID:227961", "title": "Natural killing in estrogen-treated mice responds poorly to poly I.C despite normal stimulation of circulating interferon.", "content": "Natural killing by mouse spleen cells can be stimulated in vivo by interferon or by agents that stimulate interferon, such as poly I.C. Natural killing can be suppressed in vivo by the sustained administration of 17 beta-estradiol. In BALB/c mice that had been treated with 17 beta-estradiol for 10 weeks, natural killing did not respond to intravenous poly I.C, although stimulation of circulating interferon was equal to controls. Estradiol, then, does not block interferon production but does suppress the response of natural killer cells to interferon. It is suggested that estrogens either block the maturation of natural killer cells or reduce the number of natural killer cell precursors.", "contents": "Natural killing in estrogen-treated mice responds poorly to poly I.C despite normal stimulation of circulating interferon. Natural killing by mouse spleen cells can be stimulated in vivo by interferon or by agents that stimulate interferon, such as poly I.C. Natural killing can be suppressed in vivo by the sustained administration of 17 beta-estradiol. In BALB/c mice that had been treated with 17 beta-estradiol for 10 weeks, natural killing did not respond to intravenous poly I.C, although stimulation of circulating interferon was equal to controls. Estradiol, then, does not block interferon production but does suppress the response of natural killer cells to interferon. It is suggested that estrogens either block the maturation of natural killer cells or reduce the number of natural killer cell precursors."}
{"id": "PMID:227962", "title": "Immobilization of viral and mycoplasma antigens and of immunoglobulins on polystyrene surface for immunoassays.", "content": "The immobilization of purified influenza virus, rubella virus, crude nuclear cytomegalovirus antigen and of mycoplasma on polystyrene tubes was studied using radio-iodinated preparations. The antigen activities on tube surfaces were determined using sequentially specific human antibodies and alkaline phosphatase-conjugated anti-human IgG in an enzyme-immunoassay (EIA) reaction. In addition, immobilization of radio-iodinated human IgG, IgM, and IgA, serving as model proteins, was studied using the respective anti-immunoglobulin conjugates in EIA directly. Pretreatment of the surface with albumin and glutaraldehyde inhibited the adsorption and antigenicity of IgG. Increase of temperature and thus of speed of adsorption did not affect the fraction of antigen eluted during the test procedure. Only with IgG and IgA was it necessary to saturate the polystyrene surface in order to achieve maximal reactivity in EIA. With other antigens, maximal reactivity in EIA was obtained with amounts of protein much lower than the maximal amount that could be adsorbed per tube. IgM was found to have an exceptionally high affinity to polystyrene.", "contents": "Immobilization of viral and mycoplasma antigens and of immunoglobulins on polystyrene surface for immunoassays. The immobilization of purified influenza virus, rubella virus, crude nuclear cytomegalovirus antigen and of mycoplasma on polystyrene tubes was studied using radio-iodinated preparations. The antigen activities on tube surfaces were determined using sequentially specific human antibodies and alkaline phosphatase-conjugated anti-human IgG in an enzyme-immunoassay (EIA) reaction. In addition, immobilization of radio-iodinated human IgG, IgM, and IgA, serving as model proteins, was studied using the respective anti-immunoglobulin conjugates in EIA directly. Pretreatment of the surface with albumin and glutaraldehyde inhibited the adsorption and antigenicity of IgG. Increase of temperature and thus of speed of adsorption did not affect the fraction of antigen eluted during the test procedure. Only with IgG and IgA was it necessary to saturate the polystyrene surface in order to achieve maximal reactivity in EIA. With other antigens, maximal reactivity in EIA was obtained with amounts of protein much lower than the maximal amount that could be adsorbed per tube. IgM was found to have an exceptionally high affinity to polystyrene."}
{"id": "PMID:227963", "title": "Detection of virus and cellular-determined antigens in situ using [125I]protein A and autoradiography.", "content": "The present paper describes the use of [125I]Protein A, isolated from Staphylococcus aureus, in detecting antigen-antibody complexes by autoradiography on single cells. the method is relatively quick, reproducible, potentially more sensitive than immunofluorescence, and should be useful in combination with conventional radioimmuno-assays. We have used it to detect the cellular expression of IgM, kappa, lambda, and beta 2-microglobulin, as well as the expression of Epstein-Barr Virus (EBV)-associated antigens expressed in human lymphoblastoid cell lines.", "contents": "Detection of virus and cellular-determined antigens in situ using [125I]protein A and autoradiography. The present paper describes the use of [125I]Protein A, isolated from Staphylococcus aureus, in detecting antigen-antibody complexes by autoradiography on single cells. the method is relatively quick, reproducible, potentially more sensitive than immunofluorescence, and should be useful in combination with conventional radioimmuno-assays. We have used it to detect the cellular expression of IgM, kappa, lambda, and beta 2-microglobulin, as well as the expression of Epstein-Barr Virus (EBV)-associated antigens expressed in human lymphoblastoid cell lines."}
{"id": "PMID:227964", "title": "Periodate or glutaraldehyde for preparing peroxidase conjugates?", "content": "Conjugates of horseradish peroxidase with antibodies (anti-human IgG (H + L)) or their Fab' fragments were prepared according to the newest modification of the periodate (P-) method or the two-step glutaraldehyde (G-) method. The conjugates were analysed by gel chromatography and subsequently tested in three different applications. For tissue immunohistochemistry on sections of lupus erythematosus skin, G-conjugates were preferred to polymeric P-conjugates. In ELISA for detection of human antibodies against penicillin P-conjugates were superior to G-conjugates. For the detection of surface Ig on lymphoid cells both types of conjugate were more or less equally suitable. A scheme for the most suitable combinations of method of preparation and field of application is given.", "contents": "Periodate or glutaraldehyde for preparing peroxidase conjugates? Conjugates of horseradish peroxidase with antibodies (anti-human IgG (H + L)) or their Fab' fragments were prepared according to the newest modification of the periodate (P-) method or the two-step glutaraldehyde (G-) method. The conjugates were analysed by gel chromatography and subsequently tested in three different applications. For tissue immunohistochemistry on sections of lupus erythematosus skin, G-conjugates were preferred to polymeric P-conjugates. In ELISA for detection of human antibodies against penicillin P-conjugates were superior to G-conjugates. For the detection of surface Ig on lymphoid cells both types of conjugate were more or less equally suitable. A scheme for the most suitable combinations of method of preparation and field of application is given."}
{"id": "PMID:227966", "title": "Characterization of human papillomavirus 3 in warts of a renal allograft patient.", "content": "Multiple flat wart-like lesions of a renal allograft recipient were shown to contain HPV 3 or a serologically crossreacting virus by indirect immunofluorescence with monospecific animal antisera against HPV [1--5]. The patient's serum revealed virus specific antibodies (immunofluorescence titer 1/80). Papillomaviruses were isolated and after in vitro iodination 3 major proteins (MW 70.000, 56.000 and 43.000) were detected by SDS polyacryalmide gel electrophoresis. DNA was extracted from the warts and cleaved with the restriction endonuclease Hae III. Distinct bands were discernible within the background of cellular DNA and these fragments were identified as papillomavirus DNA by blot hypbridization with 32P-labeled viral DNA.", "contents": "Characterization of human papillomavirus 3 in warts of a renal allograft patient. Multiple flat wart-like lesions of a renal allograft recipient were shown to contain HPV 3 or a serologically crossreacting virus by indirect immunofluorescence with monospecific animal antisera against HPV [1--5]. The patient's serum revealed virus specific antibodies (immunofluorescence titer 1/80). Papillomaviruses were isolated and after in vitro iodination 3 major proteins (MW 70.000, 56.000 and 43.000) were detected by SDS polyacryalmide gel electrophoresis. DNA was extracted from the warts and cleaved with the restriction endonuclease Hae III. Distinct bands were discernible within the background of cellular DNA and these fragments were identified as papillomavirus DNA by blot hypbridization with 32P-labeled viral DNA."}
{"id": "PMID:227968", "title": "The influence of defective-interfering particles of the PR-8 strain of influenza A virus on the pathogenesis of pulmonary infection in mice.", "content": "Homologous autointerference mediated by defective-interfering (DI) particles was first described with the PR-8 strain of influenza virus. However, little is actually known about the influence of DI particles of influenza virus on the pathogenesis of pulmonary infection. The present studies were designed to determine (1) the requirements for successful autointerference in vivo with DI particle-enriched PR-8 influenza virus and (2) the effects of DI particle-enriched virus on the development and progression of otherwise lethal pulmonary infection in mice. PR-8 influenza virus passaged in chicken eggs, but not that passaged in Madin-Darby bovine kidney cells, and enriched in DI particles markedly attenuated pulmonary infection in seven-week-old Swiss and four-week-old C57B16/Cr mice but not in three- to four-week-old Swiss mice. In addition, replication of influenza virus, straining of viral antigen, and numbers of infiltrates in lungs of mice infected with DI particle-enriched influenza virus were reduced in comparison with values in mice infected with comparable amounts of wild-type influenza virus. The protection mediated by DI particle-enriched virus appeared to be related to augmented humoral immune responses in infected mice rather than to autointerference with replication of wild-type virus.", "contents": "The influence of defective-interfering particles of the PR-8 strain of influenza A virus on the pathogenesis of pulmonary infection in mice. Homologous autointerference mediated by defective-interfering (DI) particles was first described with the PR-8 strain of influenza virus. However, little is actually known about the influence of DI particles of influenza virus on the pathogenesis of pulmonary infection. The present studies were designed to determine (1) the requirements for successful autointerference in vivo with DI particle-enriched PR-8 influenza virus and (2) the effects of DI particle-enriched virus on the development and progression of otherwise lethal pulmonary infection in mice. PR-8 influenza virus passaged in chicken eggs, but not that passaged in Madin-Darby bovine kidney cells, and enriched in DI particles markedly attenuated pulmonary infection in seven-week-old Swiss and four-week-old C57B16/Cr mice but not in three- to four-week-old Swiss mice. In addition, replication of influenza virus, straining of viral antigen, and numbers of infiltrates in lungs of mice infected with DI particle-enriched influenza virus were reduced in comparison with values in mice infected with comparable amounts of wild-type influenza virus. The protection mediated by DI particle-enriched virus appeared to be related to augmented humoral immune responses in infected mice rather than to autointerference with replication of wild-type virus."}
{"id": "PMID:227969", "title": "Effect of antiviral lipids, heat, and freezing on the activity of viruses in human milk.", "content": "Semliki Forest virus (SFV), herpes simplex virus type 1 (HSV-1), coxsackievirus B4, and cytomegalovirus (CMV) were added to human milk, which was then subjected to treatments that approximated those required for the decontamination or storage of milk. Boiling was the only treatment that eliminated these viruses from the milk. Pasteurization (at 62.5 C for 30 min) did destroy CMV, but the other viruses could still be detected. All of the viruses except HSV-1 were detectable after the contaminated milk samples had been stored at -15 C for 10 days. SFV, HSV-1, and CMV were also decreased by lipid antiviral activity, which was present in 78% of samples that were obtained on day 5 postpartum. Naturally excreted CMV was detected at the highest levels in milk that lacked this antiviral factor; this CMV also survived freezing for 10 days. Thus, whereas the lipid antiviral activity decreased the level of enveloped viruses, whether they were added to or naturally excreted into human milk, further reduction in the levels of these viruses required heat treatment.", "contents": "Effect of antiviral lipids, heat, and freezing on the activity of viruses in human milk. Semliki Forest virus (SFV), herpes simplex virus type 1 (HSV-1), coxsackievirus B4, and cytomegalovirus (CMV) were added to human milk, which was then subjected to treatments that approximated those required for the decontamination or storage of milk. Boiling was the only treatment that eliminated these viruses from the milk. Pasteurization (at 62.5 C for 30 min) did destroy CMV, but the other viruses could still be detected. All of the viruses except HSV-1 were detectable after the contaminated milk samples had been stored at -15 C for 10 days. SFV, HSV-1, and CMV were also decreased by lipid antiviral activity, which was present in 78% of samples that were obtained on day 5 postpartum. Naturally excreted CMV was detected at the highest levels in milk that lacked this antiviral factor; this CMV also survived freezing for 10 days. Thus, whereas the lipid antiviral activity decreased the level of enveloped viruses, whether they were added to or naturally excreted into human milk, further reduction in the levels of these viruses required heat treatment."}
{"id": "PMID:227970", "title": "Common exposure outbreak of gastroenteritis due to type 2 rotavirus with high secondary attack rate within families.", "content": "A sharp outbreak of gastroenteritis associated with human rotavirus type 2 involved not only all of nine infants and young children in a playgroup but also seven of 10 parents and grandparents studied. The source of the outbreak appeared to be two non-playgroup siblings. Six of 11 individuals studied shed human rotavirus type 2, and each of seven from whom paired sera were obtained developed a type 2 sero-response. Overall, evidence of infection with rotavirus type 2 was demonstrated in 10 of 11 individuals by detection of virus in stools and/or a serologic response in an enzyme-linked immunosorbent assay.", "contents": "Common exposure outbreak of gastroenteritis due to type 2 rotavirus with high secondary attack rate within families. A sharp outbreak of gastroenteritis associated with human rotavirus type 2 involved not only all of nine infants and young children in a playgroup but also seven of 10 parents and grandparents studied. The source of the outbreak appeared to be two non-playgroup siblings. Six of 11 individuals studied shed human rotavirus type 2, and each of seven from whom paired sera were obtained developed a type 2 sero-response. Overall, evidence of infection with rotavirus type 2 was demonstrated in 10 of 11 individuals by detection of virus in stools and/or a serologic response in an enzyme-linked immunosorbent assay."}
{"id": "PMID:227971", "title": "Occurrence of infection with group B coxsackievirus in rheumatic and nonrheumatic Filipino children.", "content": "The pathogenesis of rheumatic fever has been linked to various immune mechanisms involving streptococcal antibodies and heart tissue antigens. Latent myocarditis due to group B coxsackievirus has also been considered as a possible conditioning factor. The validity of the role of infection with group B coxsackievirus in rheumatic fever was tested by determining the incidence of type-specific neutralizing antibodies in sera of Filipino children. Analysis of the results by means of a normal Z-test showed that the incidence in rheumatic children was not statistically significant in comparison to the incidence in asymptomatic children.", "contents": "Occurrence of infection with group B coxsackievirus in rheumatic and nonrheumatic Filipino children. The pathogenesis of rheumatic fever has been linked to various immune mechanisms involving streptococcal antibodies and heart tissue antigens. Latent myocarditis due to group B coxsackievirus has also been considered as a possible conditioning factor. The validity of the role of infection with group B coxsackievirus in rheumatic fever was tested by determining the incidence of type-specific neutralizing antibodies in sera of Filipino children. Analysis of the results by means of a normal Z-test showed that the incidence in rheumatic children was not statistically significant in comparison to the incidence in asymptomatic children."}
{"id": "PMID:227972", "title": "Comparative prevalence of subclinical cytomegalovirus and herpes simplex virus infections in the genital and urinary tracts of low-income, urban women.", "content": "The prevalence of subclinical infections caused by cytomegaloviruses (CMV) and herpes simplex viruses (HSV) was assessed simultaneously in the genital and urinary tracts of 1,101 indigent women. Shedding of CMV from the genital and urinary tracts exceeded that of HSV by ninefold (8.89% vs. 0.95) and sevenfold (3.8% vs. 0.51%), respectively. Pregnancy, regardless of gestational age, had no discernible influence on productive infection with either virus in either the genital or the urinary tract. In contrast, age was a significant variable, especially with CMV. The prevalence of CMV shedding decreased steadily with age, from peak values of 15% and 8% in the genital and urinary tracts, respectively, of females 11-14 years of age to undetectable levels in females 31 years of age and older. Productive HSV infection was more prevalent in postmenopausal than in premenopausal women: 2.4% vs. 0.8% and 3.1% vs. 0.2% in the genital and urinary tracts, respectively. Likewise, HSV infection of both the genital and the urinary tract combined was more common in older than in younger females.", "contents": "Comparative prevalence of subclinical cytomegalovirus and herpes simplex virus infections in the genital and urinary tracts of low-income, urban women. The prevalence of subclinical infections caused by cytomegaloviruses (CMV) and herpes simplex viruses (HSV) was assessed simultaneously in the genital and urinary tracts of 1,101 indigent women. Shedding of CMV from the genital and urinary tracts exceeded that of HSV by ninefold (8.89% vs. 0.95) and sevenfold (3.8% vs. 0.51%), respectively. Pregnancy, regardless of gestational age, had no discernible influence on productive infection with either virus in either the genital or the urinary tract. In contrast, age was a significant variable, especially with CMV. The prevalence of CMV shedding decreased steadily with age, from peak values of 15% and 8% in the genital and urinary tracts, respectively, of females 11-14 years of age to undetectable levels in females 31 years of age and older. Productive HSV infection was more prevalent in postmenopausal than in premenopausal women: 2.4% vs. 0.8% and 3.1% vs. 0.2% in the genital and urinary tracts, respectively. Likewise, HSV infection of both the genital and the urinary tract combined was more common in older than in younger females."}
{"id": "PMID:227973", "title": "[Scanning electron microscopic observations of calcium pyrophosphate crystals of joint tissues and synovial fluid (author's transl)].", "content": "The deposition and ultrastructure of calcium pyrophosphate (CPPD) crystals in joint tissues of pseudogout patients and cadavers were studied. Nine calcified menisci, 2 articular cartilages and 6 samples of synovial fluid were examined by scanning electron microscopy (SEM). Some of them were examined by analytical electron microscopy (EMMA). In the samples of menisci and cartilages, the findings were compared with those in the soft X-ray examinations and polarized light microscopy. The results are summarized as follows: 1) SEM observation of the cut surfaces of calcified menisci and cartilages showed a three-dimensional ultrastructure for the CPPD crystals. The crystals in the synovial fluid taken from pseudogout knees were also clearly demonstrated by this method. The EMMA analysis provided the possibility to examine the structure and content of the crystals simultaneously. 2) Crystal deposition in the meniscus varied with the depth of the tissues; it was diffuse in the collagen framework of the superficial layer, but showed accumulation in the deep layer where a clear line of demarcation between the collagen framework and crystals was seen. 3) The crystals in the meniscus were rod, granular or rectangular in shape, and 0.2-6.5 micro by 0.2-3.5 micro in size. Crystals from the articular cartilage were granular or rod-like in shape, and 0.2-3.5 micro by 0.2-1.0 micro in size. Most of the crystals found in the synovial fluid were rod-shaped. 4) X-ray microanalysis of the meniscus crystals by EMMA showed the same pattern of PK alpha, CaK alpha, and CaK beta content as that of CPPD crystals commercially available. The P/Ca ratio was about 0.7. 5) SEM and EMMA examination can be very useful for accurate identification of the form and content of the tiny crystals in joint tissues and synovial fluid. This can also be useful in proving a diagnosis of crystal-induced synovitis.", "contents": "[Scanning electron microscopic observations of calcium pyrophosphate crystals of joint tissues and synovial fluid (author's transl)]. The deposition and ultrastructure of calcium pyrophosphate (CPPD) crystals in joint tissues of pseudogout patients and cadavers were studied. Nine calcified menisci, 2 articular cartilages and 6 samples of synovial fluid were examined by scanning electron microscopy (SEM). Some of them were examined by analytical electron microscopy (EMMA). In the samples of menisci and cartilages, the findings were compared with those in the soft X-ray examinations and polarized light microscopy. The results are summarized as follows: 1) SEM observation of the cut surfaces of calcified menisci and cartilages showed a three-dimensional ultrastructure for the CPPD crystals. The crystals in the synovial fluid taken from pseudogout knees were also clearly demonstrated by this method. The EMMA analysis provided the possibility to examine the structure and content of the crystals simultaneously. 2) Crystal deposition in the meniscus varied with the depth of the tissues; it was diffuse in the collagen framework of the superficial layer, but showed accumulation in the deep layer where a clear line of demarcation between the collagen framework and crystals was seen. 3) The crystals in the meniscus were rod, granular or rectangular in shape, and 0.2-6.5 micro by 0.2-3.5 micro in size. Crystals from the articular cartilage were granular or rod-like in shape, and 0.2-3.5 micro by 0.2-1.0 micro in size. Most of the crystals found in the synovial fluid were rod-shaped. 4) X-ray microanalysis of the meniscus crystals by EMMA showed the same pattern of PK alpha, CaK alpha, and CaK beta content as that of CPPD crystals commercially available. The P/Ca ratio was about 0.7. 5) SEM and EMMA examination can be very useful for accurate identification of the form and content of the tiny crystals in joint tissues and synovial fluid. This can also be useful in proving a diagnosis of crystal-induced synovitis."}
{"id": "PMID:227976", "title": "Effect of chlorpromazine on hepatic perfusion and bile secretory function in the isolated perfused rat liver.", "content": "The hepatotoxicity of CPZ was studied in the isolated perfused rat liver in order to more closely define possible mechanisms of phenothiazine-induced cholestasis. Perfusate concentrations of CPZ were increased from 5 x 10(-6) M to 5 x 10(-4) M until bile secretion was significantly inhibited. Measurements were then made of determinants of bile secretory function, including the magnitude of lobar distribution of perfusate flow, BAIF, and liver plasma membrane enzyme activity, Na+,K+-ATPase, Mg++-ATPase and 5'-nucleotidase. BAIF diminished significantly from control values of 1.76 +/- 0.07 microliter min-1gm-1 of liver to 1.34 +/- 0.15 and 0.80 +/- 0.09 following 2.5 and 5 x 10(-4) M CPZ, respectively. Perfusate flow also diminished from 5.64 +/- 0.44 to 1.24 +/- 0.12 ml min-1 gm-1 of liver 20 min following 5 x 10(-4) M CPZ and was associated with reduced flow to peripheral areas of the hepatic lobes as demonstrated by Tc-HAM. By 30 min, perfusate flow had returned to baseline values. CPZ also transiently diminished the excretion of bile acids in livers receiving a constant infusion of 40 mumol hr-1 sodium taurocholate. Defects in hepatic perfusion could not account entirely for the impairment in BAIF, since comparable mechanical restriction of perfusate flow in controls only diminished BAIF to 1.49 +/- 0.08 microliter min-1gm-1 of liver. CPZ signofocamt;u rediced tje secofoc actovotu pf Mg++-ATPase and 5'-nucleotidase but did not affect Na+,K+-ATPase in liver plasma membrane isolated 20 min after 5 x 10(-4) M CPZ. CPZ also resulted in a profound shift in the recovery of protein in isolated liver plasma membrane fractions from the light (density = 1.16) to heavier (density = 1.18) fractions. These findings, together with previous observations demonstrating alterations in hepatic ultrastructure, indicate that CPZ interacts in a complex manner with hepatocyte plasma and cytoplasmic membrane components and suggest that these drug-membrane interactions independently result in diminished hepatic perfusion, impairment of bile acid excretion, and inhibition of bile acid-independent bile secretion.", "contents": "Effect of chlorpromazine on hepatic perfusion and bile secretory function in the isolated perfused rat liver. The hepatotoxicity of CPZ was studied in the isolated perfused rat liver in order to more closely define possible mechanisms of phenothiazine-induced cholestasis. Perfusate concentrations of CPZ were increased from 5 x 10(-6) M to 5 x 10(-4) M until bile secretion was significantly inhibited. Measurements were then made of determinants of bile secretory function, including the magnitude of lobar distribution of perfusate flow, BAIF, and liver plasma membrane enzyme activity, Na+,K+-ATPase, Mg++-ATPase and 5'-nucleotidase. BAIF diminished significantly from control values of 1.76 +/- 0.07 microliter min-1gm-1 of liver to 1.34 +/- 0.15 and 0.80 +/- 0.09 following 2.5 and 5 x 10(-4) M CPZ, respectively. Perfusate flow also diminished from 5.64 +/- 0.44 to 1.24 +/- 0.12 ml min-1 gm-1 of liver 20 min following 5 x 10(-4) M CPZ and was associated with reduced flow to peripheral areas of the hepatic lobes as demonstrated by Tc-HAM. By 30 min, perfusate flow had returned to baseline values. CPZ also transiently diminished the excretion of bile acids in livers receiving a constant infusion of 40 mumol hr-1 sodium taurocholate. Defects in hepatic perfusion could not account entirely for the impairment in BAIF, since comparable mechanical restriction of perfusate flow in controls only diminished BAIF to 1.49 +/- 0.08 microliter min-1gm-1 of liver. CPZ signofocamt;u rediced tje secofoc actovotu pf Mg++-ATPase and 5'-nucleotidase but did not affect Na+,K+-ATPase in liver plasma membrane isolated 20 min after 5 x 10(-4) M CPZ. CPZ also resulted in a profound shift in the recovery of protein in isolated liver plasma membrane fractions from the light (density = 1.16) to heavier (density = 1.18) fractions. These findings, together with previous observations demonstrating alterations in hepatic ultrastructure, indicate that CPZ interacts in a complex manner with hepatocyte plasma and cytoplasmic membrane components and suggest that these drug-membrane interactions independently result in diminished hepatic perfusion, impairment of bile acid excretion, and inhibition of bile acid-independent bile secretion."}
{"id": "PMID:227977", "title": "Decreased nitroblue tetrazolium reduction of granulocytes in type IV hyperlipoproteinemia.", "content": "NBT reduction of granulocytes was determined in 40 patients with primary hyperlipoproteinemia. The reaction was measured in granulocytes both in the resting state and after stimulation with E. coli, as well as with and without addition of plasma. In 17 patients with type IV hyperlipoproteinemia (endogenous hypertriglyceridemia), the NBT reduction was significantly decreased in all these types of experiments when compared with 12 healthy controls. Sera from hypertriglyceridemic patients decreased NBT reduction of normal granulocytes. Increasing concentration of VLDLs from normolipidemic donors had the same effect. It is suggested that plasma lipoproteins may influence granulocyte function.", "contents": "Decreased nitroblue tetrazolium reduction of granulocytes in type IV hyperlipoproteinemia. NBT reduction of granulocytes was determined in 40 patients with primary hyperlipoproteinemia. The reaction was measured in granulocytes both in the resting state and after stimulation with E. coli, as well as with and without addition of plasma. In 17 patients with type IV hyperlipoproteinemia (endogenous hypertriglyceridemia), the NBT reduction was significantly decreased in all these types of experiments when compared with 12 healthy controls. Sera from hypertriglyceridemic patients decreased NBT reduction of normal granulocytes. Increasing concentration of VLDLs from normolipidemic donors had the same effect. It is suggested that plasma lipoproteins may influence granulocyte function."}
{"id": "PMID:227979", "title": "Central generation of bursting in the feeding system of the snail, Lymnaea stagnalis.", "content": "The central generation of burst activity was investigated in the buccal ganglia of Lymnaea. Eight different patterns of burst activity were generated by one or two consecutive phases of compound synaptic potentials resulting from activity of neurones. These inputs acted upon the different endogenous properties of buccal neurones such as post-inhibitory rebound and spike adaptation. Effects of synaptic inputs were reinforced by by electrotonic coupling of some buccal neurones of the same type.", "contents": "Central generation of bursting in the feeding system of the snail, Lymnaea stagnalis. The central generation of burst activity was investigated in the buccal ganglia of Lymnaea. Eight different patterns of burst activity were generated by one or two consecutive phases of compound synaptic potentials resulting from activity of neurones. These inputs acted upon the different endogenous properties of buccal neurones such as post-inhibitory rebound and spike adaptation. Effects of synaptic inputs were reinforced by by electrotonic coupling of some buccal neurones of the same type."}
{"id": "PMID:227980", "title": "Synthetic phospholipid vesicles containing a purified viral antigen and cell membrane proteins stimulate the development of cytotoxic T lymphocytes.", "content": "Synthetic phospholipid vesicles (liposomes) containing the purified glycoprotein (G) of vesicular stomatitis virus (VSV) and solubilized membrane proteins from cells of the appropriate H-2 haplotype elicited H-2-restricted cytotoxic T lymphocytes (CTL) that lysed VSV-infected target cells. The CTL were elicited by intact liposomes, not by released components. Thus, when spleen cells from VSV-primed H-2d X H-2b hybrid mice were stimulated with liposomes having G protein + membrane proteins from cells with one of the parental H-2 haplotypes, the resulting CTL lysed only VSV-infected target cells with that parent's H-2 type. This result argues against the view that T cells in general recognize only processed antigenic fragments on macrophages. Moreover, liposomes were only effective when G protein and cell membrane proteins were included in the same vesicles. This result suggests that for effective interaction with CTL precursors the antigen (G protein) and products of the H-2 complex must be closer to each other than 600--1,000 angstrom, the diameter of the lipid vesicles used in this study.", "contents": "Synthetic phospholipid vesicles containing a purified viral antigen and cell membrane proteins stimulate the development of cytotoxic T lymphocytes. Synthetic phospholipid vesicles (liposomes) containing the purified glycoprotein (G) of vesicular stomatitis virus (VSV) and solubilized membrane proteins from cells of the appropriate H-2 haplotype elicited H-2-restricted cytotoxic T lymphocytes (CTL) that lysed VSV-infected target cells. The CTL were elicited by intact liposomes, not by released components. Thus, when spleen cells from VSV-primed H-2d X H-2b hybrid mice were stimulated with liposomes having G protein + membrane proteins from cells with one of the parental H-2 haplotypes, the resulting CTL lysed only VSV-infected target cells with that parent's H-2 type. This result argues against the view that T cells in general recognize only processed antigenic fragments on macrophages. Moreover, liposomes were only effective when G protein and cell membrane proteins were included in the same vesicles. This result suggests that for effective interaction with CTL precursors the antigen (G protein) and products of the H-2 complex must be closer to each other than 600--1,000 angstrom, the diameter of the lipid vesicles used in this study."}
{"id": "PMID:227982", "title": "A T helper cell for anti-viral cytotoxic T-cell responses.", "content": "We demonstrate here: (a) the existence of T helper (Th) cells that augment the generation of virus-specific cytotoxic T cells in vitro, (b) that the helper cells carry the theta and Ly 1 membrane antigens, (c) that activation of the Th effect is specific for viral antigens, and (d) that the delivery of help is not H-2 restricted.", "contents": "A T helper cell for anti-viral cytotoxic T-cell responses. We demonstrate here: (a) the existence of T helper (Th) cells that augment the generation of virus-specific cytotoxic T cells in vitro, (b) that the helper cells carry the theta and Ly 1 membrane antigens, (c) that activation of the Th effect is specific for viral antigens, and (d) that the delivery of help is not H-2 restricted."}
{"id": "PMID:227981", "title": "Cyclic adenosine monophosphate response to prostaglandin E2 on subpopulations of human lymphocytes.", "content": "Receptors for prostaglandin E2 or histamine were measured on subpopulations of human lymphocytes, using the cyclic AMP increase after exposure to prostaglandin or histamine as an indicator for the presence of receptors. The cyclic AMP response to prostaglandin E2 was similar in unfractionated lymphocytes and the T-enriched and T-depleted fractions. Within the T-enriched population, T cells bearing a receptor for the Fc portion of IgG (T gamma-cells) had a 27.4-fold rise in cyclic AMP after exposure to prostaglandin E2, whereas the remaining T cells (non-T gamma cells) had a fourfold increase. It would appear that prostaglandin receptors are concentrated on a small subfraction of T gamma cells, comprising approximately 15% of the T-cell population. The cyclic AMP response to histamine was less than twofold in all lymphocyte fractions.", "contents": "Cyclic adenosine monophosphate response to prostaglandin E2 on subpopulations of human lymphocytes. Receptors for prostaglandin E2 or histamine were measured on subpopulations of human lymphocytes, using the cyclic AMP increase after exposure to prostaglandin or histamine as an indicator for the presence of receptors. The cyclic AMP response to prostaglandin E2 was similar in unfractionated lymphocytes and the T-enriched and T-depleted fractions. Within the T-enriched population, T cells bearing a receptor for the Fc portion of IgG (T gamma-cells) had a 27.4-fold rise in cyclic AMP after exposure to prostaglandin E2, whereas the remaining T cells (non-T gamma cells) had a fourfold increase. It would appear that prostaglandin receptors are concentrated on a small subfraction of T gamma cells, comprising approximately 15% of the T-cell population. The cyclic AMP response to histamine was less than twofold in all lymphocyte fractions."}
{"id": "PMID:227983", "title": "[The microanalysis of serum lipoprotein lipids (author's transl)].", "content": "A method is described which allows the determination of phospholipids, free and esterified cholesterol, triglycerides and free fatty acids in lipoprotein fractions starting from 50 microliter of serum. Lipoproteins were separated by successive precipitation: VLDL with Heparin/Mg++, LDL with Dextran sulfate/Mg++ and finally HDL with Dextran sulfate/Mn++. Lipids extracted from the precipitated lipoproteins were determined gravimetrically and by densitometry after thin layer chromatography and charring (van Gent, C.M. (1968), Z. Anal. Chem. 236, 344--350; Egge, H. et al. (1970) Z. Klin. Chem. Klin. Biochem. 8, 488--491). The results obtained from the serum of 12 adult healthy persons were compared with those from lipoprotein fractions separated by preparative ultracentrifugation (Havel, R. J. et al. (1955) J. Clin. Invest. 34, 1345--1353). The distribution of lipids in beta-lipoproteins (d less than 1.063 g/ml) and HDL (1.063 less than d less than 1.21 g/ml) prepared by both methods showed good agreement. Some differences were observed between VLDL (d less than 1.006 g/ml) and VHDL (d greater than 1.21 g/ml) prepared either by precipitation or ultracentrifugation. Compared to the total lipid of the sera, recovery rates were 95--105%. Variation coefficients were in the range of 15--20% for VLDL lipids, 5--10% for LDL and HDL lipids and 10--15% for VHDL lipids. Gravimetrically determined total lipids had a variation coefficient of 4 and 6% for LDL and HDL respectively.", "contents": "[The microanalysis of serum lipoprotein lipids (author's transl)]. A method is described which allows the determination of phospholipids, free and esterified cholesterol, triglycerides and free fatty acids in lipoprotein fractions starting from 50 microliter of serum. Lipoproteins were separated by successive precipitation: VLDL with Heparin/Mg++, LDL with Dextran sulfate/Mg++ and finally HDL with Dextran sulfate/Mn++. Lipids extracted from the precipitated lipoproteins were determined gravimetrically and by densitometry after thin layer chromatography and charring (van Gent, C.M. (1968), Z. Anal. Chem. 236, 344--350; Egge, H. et al. (1970) Z. Klin. Chem. Klin. Biochem. 8, 488--491). The results obtained from the serum of 12 adult healthy persons were compared with those from lipoprotein fractions separated by preparative ultracentrifugation (Havel, R. J. et al. (1955) J. Clin. Invest. 34, 1345--1353). The distribution of lipids in beta-lipoproteins (d less than 1.063 g/ml) and HDL (1.063 less than d less than 1.21 g/ml) prepared by both methods showed good agreement. Some differences were observed between VLDL (d less than 1.006 g/ml) and VHDL (d greater than 1.21 g/ml) prepared either by precipitation or ultracentrifugation. Compared to the total lipid of the sera, recovery rates were 95--105%. Variation coefficients were in the range of 15--20% for VLDL lipids, 5--10% for LDL and HDL lipids and 10--15% for VHDL lipids. Gravimetrically determined total lipids had a variation coefficient of 4 and 6% for LDL and HDL respectively."}
{"id": "PMID:227984", "title": "Comparison of four commercially available cAMP kits.", "content": "In this study four commercially available cAMP kits were compared and shown to differ with respect to reliability, sensitivity, simplicity and expiration time. It is not possible to recommend a particular kit, because the choice depends on the demands of the investigator, which, of course, may vary. However, in our opinion, one of the kits was inferior to the others.", "contents": "Comparison of four commercially available cAMP kits. In this study four commercially available cAMP kits were compared and shown to differ with respect to reliability, sensitivity, simplicity and expiration time. It is not possible to recommend a particular kit, because the choice depends on the demands of the investigator, which, of course, may vary. However, in our opinion, one of the kits was inferior to the others."}
{"id": "PMID:227986", "title": "Feline syncytium-forming virus: DNA provirus size and structure.", "content": "An infectious DNA assay has been used to investigate the size and structure of the genome of feline syncytium-forming virus (FSFV). The dose response between DNA extracted from FSFV-infected cells and plaque number on feline embryo cells followed two-hit kinetics and the mol. wt. of the proviral DNA was estimated as approx. 6 x 10(6).", "contents": "Feline syncytium-forming virus: DNA provirus size and structure. An infectious DNA assay has been used to investigate the size and structure of the genome of feline syncytium-forming virus (FSFV). The dose response between DNA extracted from FSFV-infected cells and plaque number on feline embryo cells followed two-hit kinetics and the mol. wt. of the proviral DNA was estimated as approx. 6 x 10(6)."}
{"id": "PMID:227987", "title": "Initial interaction of human fibroblast and leukocyte interferons with FS-4 fibroblasts.", "content": "Human FS-4 cells were exposed to human fibroblast interferon for various times and further incubated in the absence of interferon until challenged with vesicular stomatitis virus. Addition of antibody to fibroblast interferon at the time of removal of interferon did not alter the development of the antiviral state. If cells were exposed to interferon for 45 min at either 0 or 37 degrees C, they developed resistance upon subsequent incubation at 37 degrees C. However, less resistance developed if the cells were initially incubated at 0 degrees C. Our results indicate that a single interaction of fibroblast interferon with susceptible cells, either at 0 or 37 degrees C, is sufficient for the subsequent development of an antiviral state, at least in the short term experiment. The kinetics of development of the antiviral state were compared with fibroblast and leukocyte interferon. The rise in the degree of antiviral resistance was steeper and maximal levels of resistance were reached sooner when FS-4 cells were incubated with increasing concentrations of fibroblast interferon than with leukocyte interferon. This suggests a greater affinity of fibroblast interferon for these cells.", "contents": "Initial interaction of human fibroblast and leukocyte interferons with FS-4 fibroblasts. Human FS-4 cells were exposed to human fibroblast interferon for various times and further incubated in the absence of interferon until challenged with vesicular stomatitis virus. Addition of antibody to fibroblast interferon at the time of removal of interferon did not alter the development of the antiviral state. If cells were exposed to interferon for 45 min at either 0 or 37 degrees C, they developed resistance upon subsequent incubation at 37 degrees C. However, less resistance developed if the cells were initially incubated at 0 degrees C. Our results indicate that a single interaction of fibroblast interferon with susceptible cells, either at 0 or 37 degrees C, is sufficient for the subsequent development of an antiviral state, at least in the short term experiment. The kinetics of development of the antiviral state were compared with fibroblast and leukocyte interferon. The rise in the degree of antiviral resistance was steeper and maximal levels of resistance were reached sooner when FS-4 cells were incubated with increasing concentrations of fibroblast interferon than with leukocyte interferon. This suggests a greater affinity of fibroblast interferon for these cells."}
{"id": "PMID:227988", "title": "A fluoroimmunoassay for measurement and visualization of antibody bound to surface antigens of HSV-infected cells.", "content": "An assay based on quantitative spectrofluorometry of surface immunofluorescence was applied to the study of reactions between antibody and surface antigens of viable HSV-infected cells in suspension. Fluorescence was expressed in terms of photon counts per second. Both the direct and indirect fluorescent antibody techniques proved acceptable for assay of surface reactions, yielding values of specific fluorescence as high as eight times those of controls. Fluorescence microscopy of cell populations assayed by spectrofluorometry allowed for simultaneous visual examination of surface antigens. Comparison of the fluoroimmunoassay with the 51Cr-release test for cytolytic antibody to HSV-induced surface antigens revealed the latter to be the more sensitive, with antibody titres ranging up to four times those detected by fluoroimmunoassay. General correlation between the two assays was found using both rabbit and human sources of antisera.", "contents": "A fluoroimmunoassay for measurement and visualization of antibody bound to surface antigens of HSV-infected cells. An assay based on quantitative spectrofluorometry of surface immunofluorescence was applied to the study of reactions between antibody and surface antigens of viable HSV-infected cells in suspension. Fluorescence was expressed in terms of photon counts per second. Both the direct and indirect fluorescent antibody techniques proved acceptable for assay of surface reactions, yielding values of specific fluorescence as high as eight times those of controls. Fluorescence microscopy of cell populations assayed by spectrofluorometry allowed for simultaneous visual examination of surface antigens. Comparison of the fluoroimmunoassay with the 51Cr-release test for cytolytic antibody to HSV-induced surface antigens revealed the latter to be the more sensitive, with antibody titres ranging up to four times those detected by fluoroimmunoassay. General correlation between the two assays was found using both rabbit and human sources of antisera."}
{"id": "PMID:227989", "title": "Rotavirus polypeptides.", "content": "Rotavirus infected monkey kidney cells (LLC-MK2) have been labelled with 35S-methionine in the presence of actinomycin D. The cells have been lysed with SDS and the polypeptides separated by discontinuous polyacrylamide gel electrophoresis. Rotavirus polypeptides began to appear 4 to 5 h p.i.; incorporation was maximum at 8 h, but all the polypeptides were still being made 15 to 18 h p.i. Tissue culture adapted calf rotavirus particles were labelled with 35S-methionine and the polypeptides compared with cell associated rotavirus polypeptides. There were four inner coat, four outer coat and three non-structural polypeptides. Several of the outer coat polypeptides have altered mol. wt. on maturation. The polypeptides of rotavirus from seven species (human, pig, calf, lamb, mouse, foal and rabbit) have been compared and their mol. wt. calculated. The polypeptides fell into the same relative groupings for each virus, but there were variations in the mol. wt. of most comparable polypeptides. The polypeptides of tissue culture adapted and non-adapted calf rotavirus from the same original isolate varied only in one of the non-structural polypeptides.", "contents": "Rotavirus polypeptides. Rotavirus infected monkey kidney cells (LLC-MK2) have been labelled with 35S-methionine in the presence of actinomycin D. The cells have been lysed with SDS and the polypeptides separated by discontinuous polyacrylamide gel electrophoresis. Rotavirus polypeptides began to appear 4 to 5 h p.i.; incorporation was maximum at 8 h, but all the polypeptides were still being made 15 to 18 h p.i. Tissue culture adapted calf rotavirus particles were labelled with 35S-methionine and the polypeptides compared with cell associated rotavirus polypeptides. There were four inner coat, four outer coat and three non-structural polypeptides. Several of the outer coat polypeptides have altered mol. wt. on maturation. The polypeptides of rotavirus from seven species (human, pig, calf, lamb, mouse, foal and rabbit) have been compared and their mol. wt. calculated. The polypeptides fell into the same relative groupings for each virus, but there were variations in the mol. wt. of most comparable polypeptides. The polypeptides of tissue culture adapted and non-adapted calf rotavirus from the same original isolate varied only in one of the non-structural polypeptides."}
{"id": "PMID:227990", "title": "Expression of retrovirus-associated 8S RNA in mammalian cells.", "content": "A comparative study of the expression of retrovirus-associated 8S RNA was made in different mammalian cells. This RNA is found in cultured cells from all mammalian species analysed but its expression varies. An increase of 8S RNA is observed in sarcoma virus-transformed cells as compared to control uninfected cells or cells infected with leukaemia virus. No increased quantities of 8S RNA were detected in cells transformed by SV40 or by methylcholanthrene. These data show that the level of 8S RNA was augmented following transformation by sarcoma viruses.", "contents": "Expression of retrovirus-associated 8S RNA in mammalian cells. A comparative study of the expression of retrovirus-associated 8S RNA was made in different mammalian cells. This RNA is found in cultured cells from all mammalian species analysed but its expression varies. An increase of 8S RNA is observed in sarcoma virus-transformed cells as compared to control uninfected cells or cells infected with leukaemia virus. No increased quantities of 8S RNA were detected in cells transformed by SV40 or by methylcholanthrene. These data show that the level of 8S RNA was augmented following transformation by sarcoma viruses."}
{"id": "PMID:227991", "title": "Acute and latent infection of sensory ganglia with herpes simplex virus: immune control and virus reactivation.", "content": "The role of antiviral antibody in controlling the acute and latent phases of herpes simplex virus (HSV) infection in sensory ganglia of mice was studied in vitro and in vivo. Organ cultures of ganglia inoculated in vitro with HSV produced infectious virus for at least 3 weeks. In the presence of antiviral antibody, the titre of virus was markedly reduced, but the infection was not eliminated. Similarly, passive administration of antibody to HSV-infected immunodeficient (nude) mice reduced the virus titre but did not eliminate the acute phase of the ganglionic infection. Suppression of the cell-mediated immune response in latently infected immunocompetent mice by treatment with cyclophosphamide and/or X-irradiation resulted in reactivation of HSV in up to 70% of the animals. Reactivation was demonstrated by recovering infectious virus in cell-free homogenates of ganglia and eye globes and by finding virus antigens in ganglia by immunofluorescent staining. Reactivation occurred both in vitro and in vivo in the presence of high concentrations of neutralizing antibody. It is concluded that antibody alone is not sufficient to eliminate the acute phase of the ganglionic infection and that cytotoxic agents known to suppress the host's cellular immune response can reactivate virus in the presence of neutralizing antibody.", "contents": "Acute and latent infection of sensory ganglia with herpes simplex virus: immune control and virus reactivation. The role of antiviral antibody in controlling the acute and latent phases of herpes simplex virus (HSV) infection in sensory ganglia of mice was studied in vitro and in vivo. Organ cultures of ganglia inoculated in vitro with HSV produced infectious virus for at least 3 weeks. In the presence of antiviral antibody, the titre of virus was markedly reduced, but the infection was not eliminated. Similarly, passive administration of antibody to HSV-infected immunodeficient (nude) mice reduced the virus titre but did not eliminate the acute phase of the ganglionic infection. Suppression of the cell-mediated immune response in latently infected immunocompetent mice by treatment with cyclophosphamide and/or X-irradiation resulted in reactivation of HSV in up to 70% of the animals. Reactivation was demonstrated by recovering infectious virus in cell-free homogenates of ganglia and eye globes and by finding virus antigens in ganglia by immunofluorescent staining. Reactivation occurred both in vitro and in vivo in the presence of high concentrations of neutralizing antibody. It is concluded that antibody alone is not sufficient to eliminate the acute phase of the ganglionic infection and that cytotoxic agents known to suppress the host's cellular immune response can reactivate virus in the presence of neutralizing antibody."}
{"id": "PMID:227992", "title": "Evidence for herpes simplex virus type-selective receptors on cellular plasma membranes.", "content": "Herpes simplex virus type 1 (HSV-1) interfered with the adsorption of subsequently added homotypic but no heterotypic HSV, suggesting that the cellular receptors involved were type-selective. Both infective and u.v.-irradiated virus could block the attachment of virions to cellular surface receptors. The adsorption rate was studied by assaying non-adsorbed infective virus remaining in the fluid medium and cell-associated 3H-thymidine labelled HSV, and HSV mutants assayed in presence of phosphonoformic acid (PFA). The adsorption profiles indicated that GMK AH-1, Vero and SIRC cells all exhibited more HSV type 1-than type 2-selective receptors while HeLa S3 cells displayed more receptors with affinity for type 2 than for type 1. On HEp-2 and human embryonic lung cells HSV type 1- and type 2-selective receptors were about equally represented.", "contents": "Evidence for herpes simplex virus type-selective receptors on cellular plasma membranes. Herpes simplex virus type 1 (HSV-1) interfered with the adsorption of subsequently added homotypic but no heterotypic HSV, suggesting that the cellular receptors involved were type-selective. Both infective and u.v.-irradiated virus could block the attachment of virions to cellular surface receptors. The adsorption rate was studied by assaying non-adsorbed infective virus remaining in the fluid medium and cell-associated 3H-thymidine labelled HSV, and HSV mutants assayed in presence of phosphonoformic acid (PFA). The adsorption profiles indicated that GMK AH-1, Vero and SIRC cells all exhibited more HSV type 1-than type 2-selective receptors while HeLa S3 cells displayed more receptors with affinity for type 2 than for type 1. On HEp-2 and human embryonic lung cells HSV type 1- and type 2-selective receptors were about equally represented."}
{"id": "PMID:227993", "title": "Characterization of interferon messenger RNA from human lymphoblastoid cells.", "content": "After treatment with Sendai virus, Namalwa cells form large amounts of interferon. RNA extracted from treated whole cells or from their polysomes was injected into Xenopus laevis oocytes and the interferon formed was titrated. The results show that the amount of interferon mRNA was maximal by 9 h after treatment of the cells with Sendai virus and then declined. Sucrose gradient centrifugation of the mRNA gave substantial purification and showed that its size was 12 S.", "contents": "Characterization of interferon messenger RNA from human lymphoblastoid cells. After treatment with Sendai virus, Namalwa cells form large amounts of interferon. RNA extracted from treated whole cells or from their polysomes was injected into Xenopus laevis oocytes and the interferon formed was titrated. The results show that the amount of interferon mRNA was maximal by 9 h after treatment of the cells with Sendai virus and then declined. Sucrose gradient centrifugation of the mRNA gave substantial purification and showed that its size was 12 S."}
{"id": "PMID:227994", "title": "Comparison of the antigens produced by foamy virus in a cytolytic and a persistent infection of HEp2 cells.", "content": "The antigens from cytolytic infections of HEp2 cells by type I simian foamy virus produced two multicomponent precipitation lines when tested by immunodiffusion with the homologous hyperimmune rabbit antiserum. The antigens obtained from a non-productive infection of MK5 virus in HEp2 cells produced only those precipitation lines which corresponded with the inner lines obtained from the cytolytic infection. Similarly, hyperimmune rabbit antiserum against antigens extracted from the persistent infection lacked the antibody which was responsible for the outer lines of precipitation. Indirect immunofluorescence with acetone-fixed and unfixed cells using the homologous and heterologous sera confirmed the absence of antigens in the persistent infection and showed that an antigen is produced in the persistently infected cells which is either absent or present in very small amounts in cytolytically infected cells. Neutralization experiments and ether treatment suggested that the missing antigens in the persistent infection were the envelope components of foamy virus. It is proposed that the persistent infection has properties in common with some infections by RNA tumour viruses.", "contents": "Comparison of the antigens produced by foamy virus in a cytolytic and a persistent infection of HEp2 cells. The antigens from cytolytic infections of HEp2 cells by type I simian foamy virus produced two multicomponent precipitation lines when tested by immunodiffusion with the homologous hyperimmune rabbit antiserum. The antigens obtained from a non-productive infection of MK5 virus in HEp2 cells produced only those precipitation lines which corresponded with the inner lines obtained from the cytolytic infection. Similarly, hyperimmune rabbit antiserum against antigens extracted from the persistent infection lacked the antibody which was responsible for the outer lines of precipitation. Indirect immunofluorescence with acetone-fixed and unfixed cells using the homologous and heterologous sera confirmed the absence of antigens in the persistent infection and showed that an antigen is produced in the persistently infected cells which is either absent or present in very small amounts in cytolytically infected cells. Neutralization experiments and ether treatment suggested that the missing antigens in the persistent infection were the envelope components of foamy virus. It is proposed that the persistent infection has properties in common with some infections by RNA tumour viruses."}
{"id": "PMID:227995", "title": "Loss of proviral DNA sequences in a revertant of Kirsten sarcoma virus-transformed murine fibroblasts.", "content": "A previously described revertant cell line (K-BALB SR1212), derived as a single cell clone from a clonal line of murine fibroblasts (K-BALB) transformed by a nonproductive infection with the Kirsten strain of murine sarcoma virus, has normal morphology and growth kinetics and, unlike the transformed parent cell line, lacks a sarcoma virus that can be rescued. We report here that this reversion correlates with low to undetectable levels of expression of cellular Ki-MSV-specific RNA and a reduction of proviral sequences in the cell DNA to a level equivalent to that found in the uninfected BALB cells with a normal phenotype. The data indicate that phenotypic reversion has occurred as a consequence of the loss of part or all of the sarcoma provirus, either by chromosomal rearrangement or provirus excision.", "contents": "Loss of proviral DNA sequences in a revertant of Kirsten sarcoma virus-transformed murine fibroblasts. A previously described revertant cell line (K-BALB SR1212), derived as a single cell clone from a clonal line of murine fibroblasts (K-BALB) transformed by a nonproductive infection with the Kirsten strain of murine sarcoma virus, has normal morphology and growth kinetics and, unlike the transformed parent cell line, lacks a sarcoma virus that can be rescued. We report here that this reversion correlates with low to undetectable levels of expression of cellular Ki-MSV-specific RNA and a reduction of proviral sequences in the cell DNA to a level equivalent to that found in the uninfected BALB cells with a normal phenotype. The data indicate that phenotypic reversion has occurred as a consequence of the loss of part or all of the sarcoma provirus, either by chromosomal rearrangement or provirus excision."}
{"id": "PMID:227996", "title": "Characterization of virus DNA synthesized in KB cells infected with two temperature-sensitive mutants of adenovirus type 5.", "content": "KB cells were infected with H5ts36 or H5ts125, two adenovirus type 5 (Ad5) mutants with a temperature-sensitive synthesis of virus DNA. Infection was started at the nonpermissive temperature and at 16 h p.i. the temperature was shifted down to the permissive temperature. Shortly after the shift-down H5ts125-infected cells showed an accumulation of purely single-stranded DNA of virus origin, which was not observed in H5ts36-infected cells. This single-stranded DNA has been characterized by hybridization and sedimentation analysis. It was found that the single-stranded DNA was derived from both complementary strands and consisted of short fragments. The observation that the single-stranded DNA accumulates in H5ts125-infected cells under conditions in which the amount of DNA binding protein is reduced, suggests that the DNA-binding protein is not only involved in initiation, but also in elongation of nascent strands.", "contents": "Characterization of virus DNA synthesized in KB cells infected with two temperature-sensitive mutants of adenovirus type 5. KB cells were infected with H5ts36 or H5ts125, two adenovirus type 5 (Ad5) mutants with a temperature-sensitive synthesis of virus DNA. Infection was started at the nonpermissive temperature and at 16 h p.i. the temperature was shifted down to the permissive temperature. Shortly after the shift-down H5ts125-infected cells showed an accumulation of purely single-stranded DNA of virus origin, which was not observed in H5ts36-infected cells. This single-stranded DNA has been characterized by hybridization and sedimentation analysis. It was found that the single-stranded DNA was derived from both complementary strands and consisted of short fragments. The observation that the single-stranded DNA accumulates in H5ts125-infected cells under conditions in which the amount of DNA binding protein is reduced, suggests that the DNA-binding protein is not only involved in initiation, but also in elongation of nascent strands."}
{"id": "PMID:227997", "title": "Protection of mice against infection with wild-type Mengo virus and an interferon sensitive mutant (IS-1) by polynucleotides and interferons.", "content": "Single-stranded polynucleotide preparations [tRNA, poly(rI) plus poly(ho5C)-copolymer] which protect mice against picornavirus infections without inducing interferon, protected mice equally against infection with an interferon-sensitive mutant (IS-1) of Mengo virus and with wild-type virus (IS+). Poly(rI) . poly(rC), and mouse macrophage interferon [i.e. serum from mice treated with poly(rI) . poly(rC)] protected mice equally against infections with the two viruses, but fibroblast interferon protected better against infection with the interferon-sensitive mutant than with the wild-type virus. These and other results indicate that: Mengo virus had a genetic locus affecting sensitivity to fibroblast but not macrophage interferon; these two types of interferon have different mechanisms of action against Mengo virus infections in mice; Mengo virus genes controlling sensitivity to fibroblast interferon may modulate disease since infection in vivo induces only fibroblast interferon; the antiviral activity of the single-stranded polynucleotides is unlikely to be mediated by induction of either macrophage or fibroblast interferon.", "contents": "Protection of mice against infection with wild-type Mengo virus and an interferon sensitive mutant (IS-1) by polynucleotides and interferons. Single-stranded polynucleotide preparations [tRNA, poly(rI) plus poly(ho5C)-copolymer] which protect mice against picornavirus infections without inducing interferon, protected mice equally against infection with an interferon-sensitive mutant (IS-1) of Mengo virus and with wild-type virus (IS+). Poly(rI) . poly(rC), and mouse macrophage interferon [i.e. serum from mice treated with poly(rI) . poly(rC)] protected mice equally against infections with the two viruses, but fibroblast interferon protected better against infection with the interferon-sensitive mutant than with the wild-type virus. These and other results indicate that: Mengo virus had a genetic locus affecting sensitivity to fibroblast but not macrophage interferon; these two types of interferon have different mechanisms of action against Mengo virus infections in mice; Mengo virus genes controlling sensitivity to fibroblast interferon may modulate disease since infection in vivo induces only fibroblast interferon; the antiviral activity of the single-stranded polynucleotides is unlikely to be mediated by induction of either macrophage or fibroblast interferon."}
{"id": "PMID:227998", "title": "Production of vesicular stomatitis virus with low infectivity by interferon-treated cells.", "content": "In cultures of Ly cells treated with 10 or 30 reference units/ml of mouse interferon there was a 30 to 200 times reduction in the production of infectious vesicular stomatitis virus (VSV); virus particle production, as measured by VSV particle associated virus RNA, virus protein, and virus transcriptase, was inhibited by, at most, six times. These results suggested that interferon-treated cells produce VSV particles with low infectivity and resemble the findings in interferon-treated cells infected with murine leukaemia viruses.", "contents": "Production of vesicular stomatitis virus with low infectivity by interferon-treated cells. In cultures of Ly cells treated with 10 or 30 reference units/ml of mouse interferon there was a 30 to 200 times reduction in the production of infectious vesicular stomatitis virus (VSV); virus particle production, as measured by VSV particle associated virus RNA, virus protein, and virus transcriptase, was inhibited by, at most, six times. These results suggested that interferon-treated cells produce VSV particles with low infectivity and resemble the findings in interferon-treated cells infected with murine leukaemia viruses."}
{"id": "PMID:227999", "title": "Orthopoxvirus strains defective in surface antigen induction.", "content": "Various strains of vaccinia, variola, whitepox, monkeypox and cowpox viruses were examined for their capacity to induce a specific early antigen detectable on the surface of infected cells. The Elstree strain of vaccinia, two strains of variola minor and white variants of cowpox and monkeypox viruses lacked the capacity to induce the antigen. Variation of the parent cowpox and monkeypox viruses to white variants was always accompanied by the loss of the antigen-inducing capacity.", "contents": "Orthopoxvirus strains defective in surface antigen induction. Various strains of vaccinia, variola, whitepox, monkeypox and cowpox viruses were examined for their capacity to induce a specific early antigen detectable on the surface of infected cells. The Elstree strain of vaccinia, two strains of variola minor and white variants of cowpox and monkeypox viruses lacked the capacity to induce the antigen. Variation of the parent cowpox and monkeypox viruses to white variants was always accompanied by the loss of the antigen-inducing capacity."}
{"id": "PMID:228000", "title": "Enhanced proliferation of endogenous virus in Chinese hamster cells associated with microtubules and the mitotic apparatus of the host cell.", "content": "Chinese hamster ovary cells harbour intracytoplasmic virus-like particles of type A which are closely associated with sites of microtubule formation. We report here the enhanced proliferation of these particles and their release at the cell membrane by using either 5-bromodeoxyuridine or dibutyryl cyclic AMP. The extracellular mature particles are similar in morphology to retroviruses of type B. Close association of the type A virus precursors with microtubule organizing centres, i.e. kinetochores, centrioles and basal bodies, and with microtubules per se, is confirmed by studying the effects of the microtubule inhibitors Colcemid and vincristine sulphate. The role of microtubules in the activation and transport of the intracytoplasmic type A particles is discussed.", "contents": "Enhanced proliferation of endogenous virus in Chinese hamster cells associated with microtubules and the mitotic apparatus of the host cell. Chinese hamster ovary cells harbour intracytoplasmic virus-like particles of type A which are closely associated with sites of microtubule formation. We report here the enhanced proliferation of these particles and their release at the cell membrane by using either 5-bromodeoxyuridine or dibutyryl cyclic AMP. The extracellular mature particles are similar in morphology to retroviruses of type B. Close association of the type A virus precursors with microtubule organizing centres, i.e. kinetochores, centrioles and basal bodies, and with microtubules per se, is confirmed by studying the effects of the microtubule inhibitors Colcemid and vincristine sulphate. The role of microtubules in the activation and transport of the intracytoplasmic type A particles is discussed."}
{"id": "PMID:228001", "title": "Production of tubular structures in Vero cells infected with herpes simplex virus type 2; effects of ultraviolet light irradiation and antimetabolites.", "content": "In order to investigate the nature of tubular structures specifically found in herpes simplex virus type 2 (HSV-2)-infected cells, the multiplication of HSV-2 was studied in Vero cells cultured in the presence of varying concentrations of cytosine arabinoside (Ara-C) and cycloheximide (CH), inhibitors of DNA synthesis and protein synthesis respectively. Ara-C, at a concentration of 60 micrograms/ml, inhibited the multiplication of HSV-2 by more than 99% and also prevented the appearance of tubular structures and virus particles in the nuclei of infected cells. Nevertheless, the synthesis of virus specific surface antigens of HSV-2-infected Vero cells was not reduced, as revealed by the fluorescent antibody technique. On the other hand, 10 micrograms/ml of CH inhibited both the appearance of tubular structures and virus particles and the synthesis of virus specific surface antigens by more than 99%. These observations strongly suggest that the appearance of tubular structures is one of the late events in the process of virus multiplication. To measure the comparative genome size needed to produce membrane antigens, tubular structures and infectious centres, the effect of u.v.-inactivation of HSV-2 on these processes was studied. After u.v.-irradiation, the capacity to induce tubular structures was inactivated at a slower rate than the capacity to form infectious centres, but at a faster rate than the induction of surface antigens. Furthermore, more tubular structures could be induced by u.v.-inactivated virus than by the non-irradiated virus which was diluted to the same infectivity as the u.v.-irradiated virus. These results indicate that expression of the entire genome is not required for the production of tubular structures.", "contents": "Production of tubular structures in Vero cells infected with herpes simplex virus type 2; effects of ultraviolet light irradiation and antimetabolites. In order to investigate the nature of tubular structures specifically found in herpes simplex virus type 2 (HSV-2)-infected cells, the multiplication of HSV-2 was studied in Vero cells cultured in the presence of varying concentrations of cytosine arabinoside (Ara-C) and cycloheximide (CH), inhibitors of DNA synthesis and protein synthesis respectively. Ara-C, at a concentration of 60 micrograms/ml, inhibited the multiplication of HSV-2 by more than 99% and also prevented the appearance of tubular structures and virus particles in the nuclei of infected cells. Nevertheless, the synthesis of virus specific surface antigens of HSV-2-infected Vero cells was not reduced, as revealed by the fluorescent antibody technique. On the other hand, 10 micrograms/ml of CH inhibited both the appearance of tubular structures and virus particles and the synthesis of virus specific surface antigens by more than 99%. These observations strongly suggest that the appearance of tubular structures is one of the late events in the process of virus multiplication. To measure the comparative genome size needed to produce membrane antigens, tubular structures and infectious centres, the effect of u.v.-inactivation of HSV-2 on these processes was studied. After u.v.-irradiation, the capacity to induce tubular structures was inactivated at a slower rate than the capacity to form infectious centres, but at a faster rate than the induction of surface antigens. Furthermore, more tubular structures could be induced by u.v.-inactivated virus than by the non-irradiated virus which was diluted to the same infectivity as the u.v.-irradiated virus. These results indicate that expression of the entire genome is not required for the production of tubular structures."}
{"id": "PMID:228002", "title": "Mouse hybrid cell lines produce antibodies to herpes simplex virus type 1.", "content": "A solid-phase radioimmunoassay procedure has been devised for the assay of antibodies produced in the mouse to herpes simplex virus type 1 (HSV-1). It is based on the adsorption of virus to flexible micro-well plates and uses radio-iodine-labelled rabbit antibody against mouse immunoglobulin to assess antibody binding. Using this assay for screening, cell hybrids have been obtained which yield monoclonal antibody to HSV-1. The hybrids are between spleen cells from hyperimmune mice and an immunoglobulin-non-secreting, azaquanine resistant myeloma cell line (NS-1). From 480 hybrid cell lines initially examined, five stable cell lines were obtained which released HSV-1-specific antibody in vitro and in vivo. Mice carrying transplants of these cell lines yield binding titres in serum of up to 1/25000. Both IgG and IgM antibodies were obtained in this way.", "contents": "Mouse hybrid cell lines produce antibodies to herpes simplex virus type 1. A solid-phase radioimmunoassay procedure has been devised for the assay of antibodies produced in the mouse to herpes simplex virus type 1 (HSV-1). It is based on the adsorption of virus to flexible micro-well plates and uses radio-iodine-labelled rabbit antibody against mouse immunoglobulin to assess antibody binding. Using this assay for screening, cell hybrids have been obtained which yield monoclonal antibody to HSV-1. The hybrids are between spleen cells from hyperimmune mice and an immunoglobulin-non-secreting, azaquanine resistant myeloma cell line (NS-1). From 480 hybrid cell lines initially examined, five stable cell lines were obtained which released HSV-1-specific antibody in vitro and in vivo. Mice carrying transplants of these cell lines yield binding titres in serum of up to 1/25000. Both IgG and IgM antibodies were obtained in this way."}
{"id": "PMID:228003", "title": "Stimulation by noradrenaline of Na+K+ ATPase in different fractions of rat brain cortex.", "content": "Distribution of Na+K+-ATPase (EC. 3.6.1.3) and its susceptibility to noradrenaline (NA) were studied on electronmicroscopically characterized subcellular fractions of rat brain cortex. The highest specific activity of NaK+-ATPase was present in synaptosomal fraction disrupted in distilled water (29.52 +/- 5.53 mumoles phosphate/mg protein/hour). In the presence of 1 mM EGTA significantly higher specific activity was determined in all fractions studied, except homogenate and synaptosome. The effect of NA was studied in concentration range from 10(-6)--10(-3) M. 10(-4) M of NA produced the highest activation of the enzyme in different fractions. Also in the presence of EGTA NA was able to increase the enzyme activity. The effect of NA was much more marked on disrupted synaptosomal fraction. No qualitative differences have been found between the Na+K+-ATPase activities exhibited by the synaptosomal fraction and by other subcellular fractions with respect to susceptibility to NA. Therefore, it seems very probable that NA might modulate neurochemical transmission not only via an effect on nerve terminals but also via stimulating other part of the neuron.", "contents": "Stimulation by noradrenaline of Na+K+ ATPase in different fractions of rat brain cortex. Distribution of Na+K+-ATPase (EC. 3.6.1.3) and its susceptibility to noradrenaline (NA) were studied on electronmicroscopically characterized subcellular fractions of rat brain cortex. The highest specific activity of NaK+-ATPase was present in synaptosomal fraction disrupted in distilled water (29.52 +/- 5.53 mumoles phosphate/mg protein/hour). In the presence of 1 mM EGTA significantly higher specific activity was determined in all fractions studied, except homogenate and synaptosome. The effect of NA was studied in concentration range from 10(-6)--10(-3) M. 10(-4) M of NA produced the highest activation of the enzyme in different fractions. Also in the presence of EGTA NA was able to increase the enzyme activity. The effect of NA was much more marked on disrupted synaptosomal fraction. No qualitative differences have been found between the Na+K+-ATPase activities exhibited by the synaptosomal fraction and by other subcellular fractions with respect to susceptibility to NA. Therefore, it seems very probable that NA might modulate neurochemical transmission not only via an effect on nerve terminals but also via stimulating other part of the neuron."}
{"id": "PMID:228004", "title": "Spectroscopic and catalytic properties of Rhus vernicifera laccase depleted in type 2 copper.", "content": "1. The type 2 copper in Rhus vernicifera laccase was completely removed without loss of other types of copper. The properties of this protein derivative and the role of type 2 copper in the catalytic action of laccase was investigated. 2. The molar extinction coefficient at 614 nm of the blue chromophore decreases from 5700 to 4700 cm-1 on removal of type 2 copper. There are no apparent absorption changes at other wavelengths in the visible or near ultraviolet region when this copper is taken away. The electron-paramagnetic-resonance (epr) parameter A parallel and the linewidth of type 1 Cu2+ decreases on removal of type 2 copper. 3. The rate of reduction of type 1 Cu2+ is not affected by removal of type 2 copper but the reduction of the two-electron acceptor is greatly impaired. These results strongly support the idea that type 1 Cu2+ is the primary site for electron transfer between substrate and enzyme and that the two-electron acceptor in the native enzyme is reduced by simultaneous electron transfer from reduced types 1 and 2 copper. 4. Reoxidation of types 1 and 3 copper and the formation of the oxygen intermediate are the same processes in native and type-2-depleted enzyme. These observations suggests that type 2 copper is not involved in the formation and rapid decay of the oxygen intermediate and that it is not necessary for the stabilization of this intermediate. 5. Two new epr signals are observed on reoxidation of reduced type-2-depleted laccase. One is temporarily formed on re-reduction of reoxidized enzyme and it is suggested that it might arise from copper, possibly type 3 copper. The other one is stable for hours and it is proposed that it might come from a modified oxygen intermediate.", "contents": "Spectroscopic and catalytic properties of Rhus vernicifera laccase depleted in type 2 copper. 1. The type 2 copper in Rhus vernicifera laccase was completely removed without loss of other types of copper. The properties of this protein derivative and the role of type 2 copper in the catalytic action of laccase was investigated. 2. The molar extinction coefficient at 614 nm of the blue chromophore decreases from 5700 to 4700 cm-1 on removal of type 2 copper. There are no apparent absorption changes at other wavelengths in the visible or near ultraviolet region when this copper is taken away. The electron-paramagnetic-resonance (epr) parameter A parallel and the linewidth of type 1 Cu2+ decreases on removal of type 2 copper. 3. The rate of reduction of type 1 Cu2+ is not affected by removal of type 2 copper but the reduction of the two-electron acceptor is greatly impaired. These results strongly support the idea that type 1 Cu2+ is the primary site for electron transfer between substrate and enzyme and that the two-electron acceptor in the native enzyme is reduced by simultaneous electron transfer from reduced types 1 and 2 copper. 4. Reoxidation of types 1 and 3 copper and the formation of the oxygen intermediate are the same processes in native and type-2-depleted enzyme. These observations suggests that type 2 copper is not involved in the formation and rapid decay of the oxygen intermediate and that it is not necessary for the stabilization of this intermediate. 5. Two new epr signals are observed on reoxidation of reduced type-2-depleted laccase. One is temporarily formed on re-reduction of reoxidized enzyme and it is suggested that it might arise from copper, possibly type 3 copper. The other one is stable for hours and it is proposed that it might come from a modified oxygen intermediate."}
{"id": "PMID:228006", "title": "Electron transfer kinetics between Rhus vernicifera stellacyanin and cytochrome c (horse heart cytochrome c and Pseudomonas cytochrome c551).", "content": "The electron transfer reactions between Rhus vernicifera stellacyanin and either horse heart cytochrome c or Pseudomonas aeruginosa cytochrome c551 were investigated by rapid reaction techniques. The time course of electron transfer is monophasic under all conditions, and thus consistent with a simple formulation of the reaction. Both stopped-flow and temperature-jump experiments yield equilibrium constants in reasonable agreement with values calculated from the redox potentials. The differences in reaction rate between the two cytochromes and stellacyanin are discussed in terms of the Marcus theory.", "contents": "Electron transfer kinetics between Rhus vernicifera stellacyanin and cytochrome c (horse heart cytochrome c and Pseudomonas cytochrome c551). The electron transfer reactions between Rhus vernicifera stellacyanin and either horse heart cytochrome c or Pseudomonas aeruginosa cytochrome c551 were investigated by rapid reaction techniques. The time course of electron transfer is monophasic under all conditions, and thus consistent with a simple formulation of the reaction. Both stopped-flow and temperature-jump experiments yield equilibrium constants in reasonable agreement with values calculated from the redox potentials. The differences in reaction rate between the two cytochromes and stellacyanin are discussed in terms of the Marcus theory."}
{"id": "PMID:228009", "title": "Familial amyloidosis with cranial neuropathy and corneal lattice dystrophy.", "content": "Five siblings of a Danish family with slowly progressive involvement of the trigeminal, facial, glossopharyngeal, accessory, and hypoglossal nerves beginning at the age of 55-65 years were examined. All had asymptomatic corneal lattice dystrophy. Clinical and electrophysiological investigations also showed evidence of slight neurogenic involvement of the limbs. Conduction velocity along sensory nerves was normal but amplitude of sensory potentials was severely reduced suggesting an axonal affection which was confirmed by sural nerve biopsy. The neuropathy was secondary to amyloidosis revealed by skin and sural nerve biopsies.", "contents": "Familial amyloidosis with cranial neuropathy and corneal lattice dystrophy. Five siblings of a Danish family with slowly progressive involvement of the trigeminal, facial, glossopharyngeal, accessory, and hypoglossal nerves beginning at the age of 55-65 years were examined. All had asymptomatic corneal lattice dystrophy. Clinical and electrophysiological investigations also showed evidence of slight neurogenic involvement of the limbs. Conduction velocity along sensory nerves was normal but amplitude of sensory potentials was severely reduced suggesting an axonal affection which was confirmed by sural nerve biopsy. The neuropathy was secondary to amyloidosis revealed by skin and sural nerve biopsies."}
{"id": "PMID:228010", "title": "Olfactory mucosa in herpes simplex encephalitis.", "content": "The olfactory mucosa was examined in three patients dying from herpes simplex encephalitis. It showed changes attributed to infection by the herpes simplex virus. It is suggested that in some patients encephalitis may be a complication of infection of the olfactory mucosa.", "contents": "Olfactory mucosa in herpes simplex encephalitis. The olfactory mucosa was examined in three patients dying from herpes simplex encephalitis. It showed changes attributed to infection by the herpes simplex virus. It is suggested that in some patients encephalitis may be a complication of infection of the olfactory mucosa."}
{"id": "PMID:228011", "title": "Ischaemic neuropathy in uraemic patients caused by bovine arteriovenous shunt.", "content": "A bovine shunt, inserted between the radial artery and cephalic vein in the upper arm for access during chronic haemodialysis, caused a distal, ischaemic neuropathy in two patients. There were electrophysiological signs of axonal degeneration of motor and sensory nerve fibres in the patient with severe ischaemia, and, of only sensory fibres in the patient with mild ischaemia. Thenar muscle blood flow studies using 133Xe were a useful measure of altered tissue perfusion. Recovery was incomplete in both cases, despite banding of the graft and improved tissue perfusion in the severe case.", "contents": "Ischaemic neuropathy in uraemic patients caused by bovine arteriovenous shunt. A bovine shunt, inserted between the radial artery and cephalic vein in the upper arm for access during chronic haemodialysis, caused a distal, ischaemic neuropathy in two patients. There were electrophysiological signs of axonal degeneration of motor and sensory nerve fibres in the patient with severe ischaemia, and, of only sensory fibres in the patient with mild ischaemia. Thenar muscle blood flow studies using 133Xe were a useful measure of altered tissue perfusion. Recovery was incomplete in both cases, despite banding of the graft and improved tissue perfusion in the severe case."}
{"id": "PMID:228012", "title": "Association between polyneuritis and multiple sclerosis.", "content": "We report two cases in which multiple sclerosis and inflammatory polyneuritis occurred separately, and suggest that this association supports the idea that the two conditions may have an aetiological link.", "contents": "Association between polyneuritis and multiple sclerosis. We report two cases in which multiple sclerosis and inflammatory polyneuritis occurred separately, and suggest that this association supports the idea that the two conditions may have an aetiological link."}
{"id": "PMID:228013", "title": "Segmental and descending influences on intraspinal thresholds of single C-fibers.", "content": "1. The effect was studied of various conditioning stimuli on the threshold of single C-fibers near their spinal terminals. Spikes were recorded in L6 and L7 dorsal root ganglia of cats. A stimulating electrode in the superficial dorsal horn delivered periodic pulses whose widths were adjusted automatically to near threshold for antidromic spike production. Most units were classified according to their adequate cutaneous stimuli, as C-mechanoreceptors, high-threshold mechanoreceptors, or polymodal nociceptors. 2. Orthodromic activity in all units increased their threshold for up to several minutes; the maximum and rate of decay depended on the amount of activity. This phenomenon parallels the hyperpolarizing afterpotential of C-fibers in peripheral nerve and, we suggest, is probably due to the aftereffect of impulses. 3. Cutaneous conditioning stimuli were applied for 10-20 s near the receptive fields of tested units, but without activating them. During the brushing of skin hair, all threshold changes were decreases; during pinching most changes were increases; during noxious heating the numbers of increases and decreases were similar. It will be necessary to analyze the responses of postsynaptic cells in order to know the physiological significance of these threshold changes. 4. Stimulation in the nucleus raphe magnus caused in half the units higher intraspinal thresholds. If this result is causally related to the previously reported inhibition of neuronal responses in the dorsal horn by the nucleus raphe magnus (NRM), then increased thresholds could reflect either direct presynaptic inhibition or facilitation of inhibitory connections. 5. No correlation between receptive-field classification and the response of terminals to natural cutaneous stimulation or stimulation of the NRM could be discovered. However, the terminals of all kinds of C-fibers differ from A-fibers in their reaction to noxious cutaneous and NRM stimulation, suggesting they are subject to a different system of control.", "contents": "Segmental and descending influences on intraspinal thresholds of single C-fibers. 1. The effect was studied of various conditioning stimuli on the threshold of single C-fibers near their spinal terminals. Spikes were recorded in L6 and L7 dorsal root ganglia of cats. A stimulating electrode in the superficial dorsal horn delivered periodic pulses whose widths were adjusted automatically to near threshold for antidromic spike production. Most units were classified according to their adequate cutaneous stimuli, as C-mechanoreceptors, high-threshold mechanoreceptors, or polymodal nociceptors. 2. Orthodromic activity in all units increased their threshold for up to several minutes; the maximum and rate of decay depended on the amount of activity. This phenomenon parallels the hyperpolarizing afterpotential of C-fibers in peripheral nerve and, we suggest, is probably due to the aftereffect of impulses. 3. Cutaneous conditioning stimuli were applied for 10-20 s near the receptive fields of tested units, but without activating them. During the brushing of skin hair, all threshold changes were decreases; during pinching most changes were increases; during noxious heating the numbers of increases and decreases were similar. It will be necessary to analyze the responses of postsynaptic cells in order to know the physiological significance of these threshold changes. 4. Stimulation in the nucleus raphe magnus caused in half the units higher intraspinal thresholds. If this result is causally related to the previously reported inhibition of neuronal responses in the dorsal horn by the nucleus raphe magnus (NRM), then increased thresholds could reflect either direct presynaptic inhibition or facilitation of inhibitory connections. 5. No correlation between receptive-field classification and the response of terminals to natural cutaneous stimulation or stimulation of the NRM could be discovered. However, the terminals of all kinds of C-fibers differ from A-fibers in their reaction to noxious cutaneous and NRM stimulation, suggesting they are subject to a different system of control."}
{"id": "PMID:228015", "title": "Synergism between BCNU and irradiation in the treatment of anaplastic gliomas. An in vivo study using the avian sarcoma virus-induced glioma model.", "content": "The therapeutic effects of irradiation, BCNU, or combined irradiation and BCNU were studied in the avian sarrcoma virus (ASV)-induced glioma model in rats. Whole-head orthovoltage radiation therapy was given in six equal fractions over 2 weeks, and BCNU was administered intraperitoneally as a single dose of 10 mg/kg. Two series of experiments were performed in order to duplicate the results. In Series I, the median survival times of the experimental groups, in days after randomization were as follows: control group (no treatment), 69; group receiving 200 rads, 84 (p less than 0.05); group receiving BCNU, 80.5 (p less than 0.1); and group receiving 2000 rads + BCNU, 112 (p less than 0.001). In Series 2, the median survival times were: control group, 73.5; group receiving 2300 rads, 85 (p less than 0.01); group receiving BCNU, 92.5 (p less than 0.025); and group receiving 2300 rads + BCNU, 123.5 (p less than 0.001). In both series, combined therapy was significantly better than either radiation or BCNU alone. This is the first time that a synergistic effect of BCNU and irradiation has been reported in an in vivo brain-tumor model and supports the clinical use of this combination in the treatment of malignant gliomas.", "contents": "Synergism between BCNU and irradiation in the treatment of anaplastic gliomas. An in vivo study using the avian sarcoma virus-induced glioma model. The therapeutic effects of irradiation, BCNU, or combined irradiation and BCNU were studied in the avian sarrcoma virus (ASV)-induced glioma model in rats. Whole-head orthovoltage radiation therapy was given in six equal fractions over 2 weeks, and BCNU was administered intraperitoneally as a single dose of 10 mg/kg. Two series of experiments were performed in order to duplicate the results. In Series I, the median survival times of the experimental groups, in days after randomization were as follows: control group (no treatment), 69; group receiving 200 rads, 84 (p less than 0.05); group receiving BCNU, 80.5 (p less than 0.1); and group receiving 2000 rads + BCNU, 112 (p less than 0.001). In Series 2, the median survival times were: control group, 73.5; group receiving 2300 rads, 85 (p less than 0.01); group receiving BCNU, 92.5 (p less than 0.025); and group receiving 2300 rads + BCNU, 123.5 (p less than 0.001). In both series, combined therapy was significantly better than either radiation or BCNU alone. This is the first time that a synergistic effect of BCNU and irradiation has been reported in an in vivo brain-tumor model and supports the clinical use of this combination in the treatment of malignant gliomas."}
{"id": "PMID:228016", "title": "Cushing's disease with pituitary apoplexy leading to hypopituitarism, empty sella, and spontaneous fracture of the dorsum sellae. Case report.", "content": "A patient with a pituitary adenoma secreting adrenocorticotropin hormone manifested panhypopituitarism after an episode of pituitary apoplexy. The previously elevated urinary levels of 17-ketogenic steroids dropped sharply, and plasma cortisol became undetectable. The apoplexy also resulted in a partially empty sella on which the dorsum sellae collapsed. Recurrent Cushing's disease developed and was cured by transsphenoidal resection of a microadenoma.", "contents": "Cushing's disease with pituitary apoplexy leading to hypopituitarism, empty sella, and spontaneous fracture of the dorsum sellae. Case report. A patient with a pituitary adenoma secreting adrenocorticotropin hormone manifested panhypopituitarism after an episode of pituitary apoplexy. The previously elevated urinary levels of 17-ketogenic steroids dropped sharply, and plasma cortisol became undetectable. The apoplexy also resulted in a partially empty sella on which the dorsum sellae collapsed. Recurrent Cushing's disease developed and was cured by transsphenoidal resection of a microadenoma."}
{"id": "PMID:228021", "title": "Unconjugated and total estriol in human amniotic fluid--changes in the ratios between the two estriol levels with advancing gestational age.", "content": "In 172 amniotic fluid samples of the early second and the third trimester from 115 normal pregnancies the concentrations of unconjugated and total estriol were measured by means of radioimmunoassay. The mean concentrations of unconjugated estriol in amniotic fluid rose from 1.22 ng./ml. in the gestational weeks 15-18 to 7.82 ng./ml. in the gestational weeks 37-40, that is 6.4 times the former value. In contrast, the mean concentrations of total estriol in amniotic fluid increased more strongly, namely from 27.51 ng./ml. in the gestational weeks 15-18 to 777.15 ng./ml. in the gestational weeks 37-40, that is 28.3 times the former value. With advancing pregnancy the proportion of unconjugated estriol to total estriol in amniotic fluid fell, obeying a significant correlation, from 4.43% in the gestational weeks 15-18 to 1.01% in the gestational weeks 37-40. The presumable reasons for this are the rising conjugation rate of estriol excreted with fetal urine, concomitant to fetal maturation, and the relative transfer diminution of unconjugated estriol from maternal plasma into amniotic fluid with the advance of gestation.", "contents": "Unconjugated and total estriol in human amniotic fluid--changes in the ratios between the two estriol levels with advancing gestational age. In 172 amniotic fluid samples of the early second and the third trimester from 115 normal pregnancies the concentrations of unconjugated and total estriol were measured by means of radioimmunoassay. The mean concentrations of unconjugated estriol in amniotic fluid rose from 1.22 ng./ml. in the gestational weeks 15-18 to 7.82 ng./ml. in the gestational weeks 37-40, that is 6.4 times the former value. In contrast, the mean concentrations of total estriol in amniotic fluid increased more strongly, namely from 27.51 ng./ml. in the gestational weeks 15-18 to 777.15 ng./ml. in the gestational weeks 37-40, that is 28.3 times the former value. With advancing pregnancy the proportion of unconjugated estriol to total estriol in amniotic fluid fell, obeying a significant correlation, from 4.43% in the gestational weeks 15-18 to 1.01% in the gestational weeks 37-40. The presumable reasons for this are the rising conjugation rate of estriol excreted with fetal urine, concomitant to fetal maturation, and the relative transfer diminution of unconjugated estriol from maternal plasma into amniotic fluid with the advance of gestation."}
{"id": "PMID:228022", "title": "Ability of aged rats to alter beta adrenergic receptors of brain in response to repeated administration of reserpine and desmethylimipramine.", "content": "Repeated administration of reserpine to 3-month-old rats produced dose-related increases in [3H]dihydroalprenolol (DHA) binding in pineal gland, cerebral cortex and cerebellum. Reserpine increased DHA binding by increasing the density of beta adrenergic receptors. Brain tissue from 24-month-old rats, however, had an impaired ability to increase receptor density in response to reserpine treatment, even in the pineal gland where the concentration of reserpine was nearly 7 times that found in the glands of young rats given the same dose on the basis of body weight. Repeated administration of desmethylimipramine decreased DHA binding in pineal glands by about 50% and in cerebral cortices by about 25%, but did not alter DHA binding in the cerebellum. The magnitude of these changes was similar in the 3- and 24-month-old rats, although the concentration of desmethylimipramine in the pineal glands and cerebral cortices of the aged rats was significantly higher than that of the young animals. The results indicate that the reserpine-induced decrease in noradrenergic input causes a compensatory increase in beta adrenergic receptor density in rat brain. They suggest further that although aged rats can decrease receptor density in response to increased adrenergic input, they have an impaired ability to increase beta adrenergic receptor density in response to decreased adrenergic input. This finding may explain the decreased density of beta adrenergic receptor found in aged rat brain.", "contents": "Ability of aged rats to alter beta adrenergic receptors of brain in response to repeated administration of reserpine and desmethylimipramine. Repeated administration of reserpine to 3-month-old rats produced dose-related increases in [3H]dihydroalprenolol (DHA) binding in pineal gland, cerebral cortex and cerebellum. Reserpine increased DHA binding by increasing the density of beta adrenergic receptors. Brain tissue from 24-month-old rats, however, had an impaired ability to increase receptor density in response to reserpine treatment, even in the pineal gland where the concentration of reserpine was nearly 7 times that found in the glands of young rats given the same dose on the basis of body weight. Repeated administration of desmethylimipramine decreased DHA binding in pineal glands by about 50% and in cerebral cortices by about 25%, but did not alter DHA binding in the cerebellum. The magnitude of these changes was similar in the 3- and 24-month-old rats, although the concentration of desmethylimipramine in the pineal glands and cerebral cortices of the aged rats was significantly higher than that of the young animals. The results indicate that the reserpine-induced decrease in noradrenergic input causes a compensatory increase in beta adrenergic receptor density in rat brain. They suggest further that although aged rats can decrease receptor density in response to increased adrenergic input, they have an impaired ability to increase beta adrenergic receptor density in response to decreased adrenergic input. This finding may explain the decreased density of beta adrenergic receptor found in aged rat brain."}
{"id": "PMID:228023", "title": "Tolerance of mice to nitrous oxide.", "content": "Mice continuously exposed to a subanesthetic dose of nitrous oxide (N2O) become tolerant to nitrous oxide, as measured by an increase in their ED50 (dose required to abolish the righting reflex in 50% of animals) for N2O. The maximum increase in ED50 is approximately 0.25 atm for mice exposed to 40, 50 or 70% N2O for 2 to 3 weeks. Mice exposed to 25% N2O for 3 weeks do not develop tolerance. Mice exhibit a withdrawal syndrome when removed from the subanesthetic environment after exposure to 40 to 70% but not 25% N2O for 3 weeks. Tolerance to 50 or 70% N2O develops within 1 week and is maximal at 2 weeks. Tolerance to nitrous oxide is lost within 6 days following removal of the animals from the subanesthetic environment. Synaptic membrane fatty acid, phospholipid, and cholesterol compositions of tolerant animals are not significantly altered.", "contents": "Tolerance of mice to nitrous oxide. Mice continuously exposed to a subanesthetic dose of nitrous oxide (N2O) become tolerant to nitrous oxide, as measured by an increase in their ED50 (dose required to abolish the righting reflex in 50% of animals) for N2O. The maximum increase in ED50 is approximately 0.25 atm for mice exposed to 40, 50 or 70% N2O for 2 to 3 weeks. Mice exposed to 25% N2O for 3 weeks do not develop tolerance. Mice exhibit a withdrawal syndrome when removed from the subanesthetic environment after exposure to 40 to 70% but not 25% N2O for 3 weeks. Tolerance to 50 or 70% N2O develops within 1 week and is maximal at 2 weeks. Tolerance to nitrous oxide is lost within 6 days following removal of the animals from the subanesthetic environment. Synaptic membrane fatty acid, phospholipid, and cholesterol compositions of tolerant animals are not significantly altered."}
{"id": "PMID:228024", "title": "Unimpaired beta adrenergic responses during prazosin administration.", "content": "We have examined insulin-induced hypoglycemia to determine whether prazosin inhibits the response to sympathetic stimulation, either centrally or at beta adrenergic receptors. Nine patients with essential hypertension were studied during administration of prazosin, hydralazine or placebo. Plasma renin activity increased significantly with hydralazine and was unchanged during prazosin administration. In response to insulin, blood glucose decreased equally with both drugs and placebo, and small increases in dopamine beta-hydroxylase occurred. Plasma renin activity and heart rate increased during hypoglycemia; the increases were greater in patients taking prazosin or hydralazine. The unimpaired responses of plasma dopamine beta-hydroxylase, renin activity and heart rate to insulin-induced hypoglycemia provide evidence that prazosin does not block either the sympathetic discharge elicited by central stimulation (hypoglycemia) or the responses mediated through beta adrenergic receptors.", "contents": "Unimpaired beta adrenergic responses during prazosin administration. We have examined insulin-induced hypoglycemia to determine whether prazosin inhibits the response to sympathetic stimulation, either centrally or at beta adrenergic receptors. Nine patients with essential hypertension were studied during administration of prazosin, hydralazine or placebo. Plasma renin activity increased significantly with hydralazine and was unchanged during prazosin administration. In response to insulin, blood glucose decreased equally with both drugs and placebo, and small increases in dopamine beta-hydroxylase occurred. Plasma renin activity and heart rate increased during hypoglycemia; the increases were greater in patients taking prazosin or hydralazine. The unimpaired responses of plasma dopamine beta-hydroxylase, renin activity and heart rate to insulin-induced hypoglycemia provide evidence that prazosin does not block either the sympathetic discharge elicited by central stimulation (hypoglycemia) or the responses mediated through beta adrenergic receptors."}
{"id": "PMID:228025", "title": "Denervation-induced changes in alpha and beta adrenergic receptors of the rat submandibular gland.", "content": "Denervation resulted in a marked increase in the beta adrenergic response and isoproterenol-stimulated cyclic adenosine 3':5'-monophosphate accumulation of dispersed cells prepared from a rat submandibular gland. This increase in beta adrenergic response was paralleled by an increase in the density of beta adrenergic receptors in membranes prepared from these glands. Denervation also produced a moderate increase in alpha adrenergic receptor density in membranes prepared from whole glands. However, the alpha adrenergic response in cells, epinephrine-induced release of potassium, appeared unaltered by denervation. Furthermore, membranes prepared from denervated dispersed cells did not show the increase in alpha adrenergic receptor density seen in membranes from an intact denervated gland. These data demonstrate that removal of noradrenergic nerve terminals affects alpha and beta adrenergic receptors differently. While it is clear that beta adrenergic membrane receptors participate in denervation-induced supersensitivity, the changes in alpha adrenergic membrane receptors are more complex and may not contribute to the supersensitivity seen after denervation. On the basis of competitive binding studies, the adrenergic receptors in membranes from intact submandibular glands were subclassified as beta-1 and alpha-2. Denervation did not alter the binding characteristics of the alpha-2 receptors in this gland, demonstrating that alpha-2 adrenergic membrane receptors can be postsynaptic in this adrenergically innervated tissue.", "contents": "Denervation-induced changes in alpha and beta adrenergic receptors of the rat submandibular gland. Denervation resulted in a marked increase in the beta adrenergic response and isoproterenol-stimulated cyclic adenosine 3':5'-monophosphate accumulation of dispersed cells prepared from a rat submandibular gland. This increase in beta adrenergic response was paralleled by an increase in the density of beta adrenergic receptors in membranes prepared from these glands. Denervation also produced a moderate increase in alpha adrenergic receptor density in membranes prepared from whole glands. However, the alpha adrenergic response in cells, epinephrine-induced release of potassium, appeared unaltered by denervation. Furthermore, membranes prepared from denervated dispersed cells did not show the increase in alpha adrenergic receptor density seen in membranes from an intact denervated gland. These data demonstrate that removal of noradrenergic nerve terminals affects alpha and beta adrenergic receptors differently. While it is clear that beta adrenergic membrane receptors participate in denervation-induced supersensitivity, the changes in alpha adrenergic membrane receptors are more complex and may not contribute to the supersensitivity seen after denervation. On the basis of competitive binding studies, the adrenergic receptors in membranes from intact submandibular glands were subclassified as beta-1 and alpha-2. Denervation did not alter the binding characteristics of the alpha-2 receptors in this gland, demonstrating that alpha-2 adrenergic membrane receptors can be postsynaptic in this adrenergically innervated tissue."}
{"id": "PMID:228039", "title": "Immunoglobulin levels and specific viral antibodies in relation to smooth-muscle antibodies in cytomegalovirus infection.", "content": "Among 17 patients with cytomegalovirus (CMV) infection smooth-muscle antibodies (SMA) of the IgM class were detected in 9 (53%) and IgG-SMA in 6 (35%), while no IgA-SMA were found. IgM-SMA were present most often and in the highest titres (10-160) in the beginning of the disease, while IgG-SMA were found both early and late during the course of infection. SMA occurred most frequently in patients with specific CMV antibodies of the IgM class and in patients with elevated serum alanine aminotransferase values, but these relationships were not significant. Elevated levels of serum IgG, IgA and IgM were found in CMV infection, and a correlation between serum IgM values and IgM-SMA titres was demonstrated (alpha less than 0.01). A similar correlation between serum IgG and IgG-SMA could not be established. These findings are in support of the assumption that IgM-SMA account for a minor part of the elevated serum IgM levels in CMV infection, but not of the hypothesis that the stimulus for antibody production is the release of antigens from liver cells.", "contents": "Immunoglobulin levels and specific viral antibodies in relation to smooth-muscle antibodies in cytomegalovirus infection. Among 17 patients with cytomegalovirus (CMV) infection smooth-muscle antibodies (SMA) of the IgM class were detected in 9 (53%) and IgG-SMA in 6 (35%), while no IgA-SMA were found. IgM-SMA were present most often and in the highest titres (10-160) in the beginning of the disease, while IgG-SMA were found both early and late during the course of infection. SMA occurred most frequently in patients with specific CMV antibodies of the IgM class and in patients with elevated serum alanine aminotransferase values, but these relationships were not significant. Elevated levels of serum IgG, IgA and IgM were found in CMV infection, and a correlation between serum IgM values and IgM-SMA titres was demonstrated (alpha less than 0.01). A similar correlation between serum IgG and IgG-SMA could not be established. These findings are in support of the assumption that IgM-SMA account for a minor part of the elevated serum IgM levels in CMV infection, but not of the hypothesis that the stimulus for antibody production is the release of antigens from liver cells."}
{"id": "PMID:228041", "title": "Estimation of gestational and skeletal age in Macaca mulatta.", "content": "Results of qualitative and quantitative studies of prenatal skeletal development in Macaca mulatta are presented. Longitudinal radiographic observations were carried out on 20 monkeys of known gestational age, beginning on 120 days of gestation until the neonatal stage of skeletal development. These studies were based on multiple uterotomies on each pregnant female. The technique described provides accurate data on prenatal bone ossification, and permits an accurate estimation of fetal age in pregnant rhesus monkeys with unknown conception dates.", "contents": "Estimation of gestational and skeletal age in Macaca mulatta. Results of qualitative and quantitative studies of prenatal skeletal development in Macaca mulatta are presented. Longitudinal radiographic observations were carried out on 20 monkeys of known gestational age, beginning on 120 days of gestation until the neonatal stage of skeletal development. These studies were based on multiple uterotomies on each pregnant female. The technique described provides accurate data on prenatal bone ossification, and permits an accurate estimation of fetal age in pregnant rhesus monkeys with unknown conception dates."}
{"id": "PMID:228042", "title": "Restoration of membrane excitability of squid giant axons by reagents activating tyrosine-tubulin ligase.", "content": "Using squid giant axon, an experimental survey was performed on restoration of the membrane excitability which had been partially suppressed. Among reagents examined, a combination of 400 mM KF, 50 micrometers tyrosine, 1 mM ATP, 1 mM Mg ions and 2 micrometers cAMP was found to induce the restoration of the excitability to a large extent. Further addition of a small amount of either porcine brain microtubule proteins or the squid axoplasm was found to support complete restoration. The experiments suggest that tubulin-tyrosine ligase contained in the porcine brain microtubule protein fraction or the squid axoplasm maintains the coupling between cytoskeletal structures and the plasma membrane.", "contents": "Restoration of membrane excitability of squid giant axons by reagents activating tyrosine-tubulin ligase. Using squid giant axon, an experimental survey was performed on restoration of the membrane excitability which had been partially suppressed. Among reagents examined, a combination of 400 mM KF, 50 micrometers tyrosine, 1 mM ATP, 1 mM Mg ions and 2 micrometers cAMP was found to induce the restoration of the excitability to a large extent. Further addition of a small amount of either porcine brain microtubule proteins or the squid axoplasm was found to support complete restoration. The experiments suggest that tubulin-tyrosine ligase contained in the porcine brain microtubule protein fraction or the squid axoplasm maintains the coupling between cytoskeletal structures and the plasma membrane."}
{"id": "PMID:228043", "title": "Increase in plasma membrane phosphodiesterase activity in contact-inhibited 3T3 cells and in phenotypically reverted SV-3T3 cells.", "content": "Contact-inhibited 3T3 mouse fibroblast cells, in contrast to logarithmically growing 3T3 cells and SV-3T3 transformed cells, have increased levels of plasma membrane-bound phosphodiesterase (oligonucleotidase, E.C.3.1.4.19; nucleotide pyrophosphatase, E.C. 3.6.1.9) activity. The increase in enzyme, recorded as increased specific activity, is reversible, as evidenced by the return to normal values following dilution of confluent 3T2 cells and re-initiation of growth. Increased enzyme activity is induced again when the cells regain the confluent state. Transformed SV-3T3 cells can be induced to mimic the contact inhibited state, including increased plasma membrane phosphodiesterase activity, by exposure to a combination of: (i) agents that are known to induce increased intracellular cAMP levels and (ii) additions of purified 3T3 or SV-3T3 plasma membranes. Additions of either alone fails to induce the increase in membrane phosphodiesterase activity, although each alone can significantly suppress cell growth, as measured by incorporation of 3H amino acids. We suggest that the elevation of plasma membrane phosphodiesterase activity may serve as a measure of conversion to the contact-inhibited state in both normal cells and phenotypically reverted transformed cells.", "contents": "Increase in plasma membrane phosphodiesterase activity in contact-inhibited 3T3 cells and in phenotypically reverted SV-3T3 cells. Contact-inhibited 3T3 mouse fibroblast cells, in contrast to logarithmically growing 3T3 cells and SV-3T3 transformed cells, have increased levels of plasma membrane-bound phosphodiesterase (oligonucleotidase, E.C.3.1.4.19; nucleotide pyrophosphatase, E.C. 3.6.1.9) activity. The increase in enzyme, recorded as increased specific activity, is reversible, as evidenced by the return to normal values following dilution of confluent 3T2 cells and re-initiation of growth. Increased enzyme activity is induced again when the cells regain the confluent state. Transformed SV-3T3 cells can be induced to mimic the contact inhibited state, including increased plasma membrane phosphodiesterase activity, by exposure to a combination of: (i) agents that are known to induce increased intracellular cAMP levels and (ii) additions of purified 3T3 or SV-3T3 plasma membranes. Additions of either alone fails to induce the increase in membrane phosphodiesterase activity, although each alone can significantly suppress cell growth, as measured by incorporation of 3H amino acids. We suggest that the elevation of plasma membrane phosphodiesterase activity may serve as a measure of conversion to the contact-inhibited state in both normal cells and phenotypically reverted transformed cells."}
{"id": "PMID:228044", "title": "Uncapping of viral messenger RNA by phosphodiesterase of fibroblast plasma membranes.", "content": "Isolated plasma membranes from mouse fibroblast lines 3T3 and its tranformant SV-3T3 contain a phosphodiesterase (oligonucleotidase, E.C. 3.1.4.19; nucleotide pyrophosphatase, E.C. 3.6.1.9) that splits capped and methylated messenger RNA obtained from both reovirus and vesicular stomatitis virus. The isolated membranes are free of demonstrable ribonuclease activity and split the mRNA to produce 7-methyl guanosine diphosphate as a product. With ATP as substrate for the phosphodiesterase enzyme, the product is AMP. Synthetic caps, AMP, ADP and ATP, but not cyclic AMP, can compete with the substrate p-nitrophenyl thymidilic acid. A possible regulatory role on messenger translation is proposed.", "contents": "Uncapping of viral messenger RNA by phosphodiesterase of fibroblast plasma membranes. Isolated plasma membranes from mouse fibroblast lines 3T3 and its tranformant SV-3T3 contain a phosphodiesterase (oligonucleotidase, E.C. 3.1.4.19; nucleotide pyrophosphatase, E.C. 3.6.1.9) that splits capped and methylated messenger RNA obtained from both reovirus and vesicular stomatitis virus. The isolated membranes are free of demonstrable ribonuclease activity and split the mRNA to produce 7-methyl guanosine diphosphate as a product. With ATP as substrate for the phosphodiesterase enzyme, the product is AMP. Synthetic caps, AMP, ADP and ATP, but not cyclic AMP, can compete with the substrate p-nitrophenyl thymidilic acid. A possible regulatory role on messenger translation is proposed."}
{"id": "PMID:228045", "title": "Combined treatment of radioresistant malignant tumors with high frequency hyperthermia and gamma-rays therapy--recent results.", "content": "From the beginning of radiotherapy, efforts have been made to improve the therapeutic effects X-rays by heat. Recently, the combined therapy of heat and X-ray therapy has gained new interest because of failures of the megavoltage therapy of solid malignant tumors. Encouraged by our own animal experiments with a Walker-tumor of rats, since 1972 we have treated 52 patients with tumors of lower sensitivity. We used decimeter waves; wave length of 69 cm and a frequency of 433.92 MHz. After preheating for 3 to 5 min we added the gamma-rays of Caesium-137 or Cobalt-60 in usual rhythms. The total dose only in few cases exceeded 6000 to 6500 rads in six to seven weeks. We observed a relatively very good response for tumors of low sensitivity. The dose was between 20 and 30% lower which in the treatment of tumors of median sensitivity is acceptable. Local recurrences are rare and occurrence of distant metastases are within the characteristic development of certain malignant tumors. A prospective study has begun.", "contents": "Combined treatment of radioresistant malignant tumors with high frequency hyperthermia and gamma-rays therapy--recent results. From the beginning of radiotherapy, efforts have been made to improve the therapeutic effects X-rays by heat. Recently, the combined therapy of heat and X-ray therapy has gained new interest because of failures of the megavoltage therapy of solid malignant tumors. Encouraged by our own animal experiments with a Walker-tumor of rats, since 1972 we have treated 52 patients with tumors of lower sensitivity. We used decimeter waves; wave length of 69 cm and a frequency of 433.92 MHz. After preheating for 3 to 5 min we added the gamma-rays of Caesium-137 or Cobalt-60 in usual rhythms. The total dose only in few cases exceeded 6000 to 6500 rads in six to seven weeks. We observed a relatively very good response for tumors of low sensitivity. The dose was between 20 and 30% lower which in the treatment of tumors of median sensitivity is acceptable. Local recurrences are rare and occurrence of distant metastases are within the characteristic development of certain malignant tumors. A prospective study has begun."}
{"id": "PMID:228046", "title": "Interactions between tectal radial cells in the red-eared turtle, Pseudemys scripta elegans: an analysis of tectal modules.", "content": "The optic tectum is a major subdivision of the visual system in reptiles. Previous studies have characterized the laminar pattern, the neuronal populations, and the afferent and efferent connections of the optic tectum in a variety of reptiles. However, little is known about the interactions that occur between neurons within the tectum. This study describes two kinds of interactions that occur between one major class of neurons, the radial cells, in the optic tectum of Pseudemys using Nissl, Golgi and electron microscopic preparations. Radial cells have somata which bear long, radially oriented apical dendrites from their upper poles and short, basal dendrites from their lower poles. They are divided into two populations on the basis of the distribution of their somata in the tectum. Deep radial cells have somata densely packed in the stratum griseum periventriculare. Their plasma membranes form casual appositions. Middle radial cells have somata scattered throughout the stratum griseum centrale and stratum fibrosum et griseum superficiale and do not contact each other. The apical dendrites of both populations of radial cells participate in vertically oriented, dendritic bundles. The plasma membranes of the dendrites in these bundles form casual appositions in the deeper tectal layers and chemical, dendrodenritic synapses within the stratum fibrosum et griseum superficiale. The synapses have clear, round synaptic vesicles and slightly asymmetric membrane densities. Thus, radial cells interact via both casual appositions and chemical synapses. These interactions suggest that radial cells may form a basic framework in the tectum. Because both populations of radial cells extend into the stratum fibrosum et griseum superficiale and stratum opticum, they may receive input from some of the same tectal afferent systems. Because the deep radial cells alone have somata and dendrites in the deep tectal layers, they may receive additional inputs that the middle radial cells do not. Neurons in the two populations interact via chemical dendrodentritic synapses, thereby forming vertically oriented modules in the tectum.", "contents": "Interactions between tectal radial cells in the red-eared turtle, Pseudemys scripta elegans: an analysis of tectal modules. The optic tectum is a major subdivision of the visual system in reptiles. Previous studies have characterized the laminar pattern, the neuronal populations, and the afferent and efferent connections of the optic tectum in a variety of reptiles. However, little is known about the interactions that occur between neurons within the tectum. This study describes two kinds of interactions that occur between one major class of neurons, the radial cells, in the optic tectum of Pseudemys using Nissl, Golgi and electron microscopic preparations. Radial cells have somata which bear long, radially oriented apical dendrites from their upper poles and short, basal dendrites from their lower poles. They are divided into two populations on the basis of the distribution of their somata in the tectum. Deep radial cells have somata densely packed in the stratum griseum periventriculare. Their plasma membranes form casual appositions. Middle radial cells have somata scattered throughout the stratum griseum centrale and stratum fibrosum et griseum superficiale and do not contact each other. The apical dendrites of both populations of radial cells participate in vertically oriented, dendritic bundles. The plasma membranes of the dendrites in these bundles form casual appositions in the deeper tectal layers and chemical, dendrodenritic synapses within the stratum fibrosum et griseum superficiale. The synapses have clear, round synaptic vesicles and slightly asymmetric membrane densities. Thus, radial cells interact via both casual appositions and chemical synapses. These interactions suggest that radial cells may form a basic framework in the tectum. Because both populations of radial cells extend into the stratum fibrosum et griseum superficiale and stratum opticum, they may receive input from some of the same tectal afferent systems. Because the deep radial cells alone have somata and dendrites in the deep tectal layers, they may receive additional inputs that the middle radial cells do not. Neurons in the two populations interact via chemical dendrodentritic synapses, thereby forming vertically oriented modules in the tectum."}
{"id": "PMID:228047", "title": "Degeneracy of the information contained in amino acid sequences: evidence from overlaid genes.", "content": "The observed gene overlays in the viruses phi X174 and SV40 show a surprising economy of information storage; two different amino acid sequences are read in different frames from the same stretch of DNA. This phenomenon appears contradictory in that the information in the two overlaid amino acid sequences is strongly interdependent, yet each of the two proteins has evolved to its own well-defined function. The contradiction can be resolved by assuming sufficiently large degeneracy of the information contents of amino acid sequences with respect to function. Such a degeneracy is familiar from homologous proteins where a given biological function is implemented by many different amino acid sequences. It is shown that the very existence of viral overlays allows to derive a lower limit for the magnitude of this degeneracy: The degeneracy is equal to, or greater than fourfold; on the average, at each position of the chain a choice of 1 out of 5 or less amino acids, and not a choice of 1 out of 20 is neccessary for constructing a protein with a specified function. In addition, the strong dependence of overlay probabilities on chain length allows the definition of a maximal length of overlays; in bacterial viruses overlay regions should be shorter than about 150 residues.", "contents": "Degeneracy of the information contained in amino acid sequences: evidence from overlaid genes. The observed gene overlays in the viruses phi X174 and SV40 show a surprising economy of information storage; two different amino acid sequences are read in different frames from the same stretch of DNA. This phenomenon appears contradictory in that the information in the two overlaid amino acid sequences is strongly interdependent, yet each of the two proteins has evolved to its own well-defined function. The contradiction can be resolved by assuming sufficiently large degeneracy of the information contents of amino acid sequences with respect to function. Such a degeneracy is familiar from homologous proteins where a given biological function is implemented by many different amino acid sequences. It is shown that the very existence of viral overlays allows to derive a lower limit for the magnitude of this degeneracy: The degeneracy is equal to, or greater than fourfold; on the average, at each position of the chain a choice of 1 out of 5 or less amino acids, and not a choice of 1 out of 20 is neccessary for constructing a protein with a specified function. In addition, the strong dependence of overlay probabilities on chain length allows the definition of a maximal length of overlays; in bacterial viruses overlay regions should be shorter than about 150 residues."}
{"id": "PMID:228048", "title": "Neurilemmoma of the parapharyngeal space. Report of three cases and review of the literature.", "content": "The clinical pre-operative diagnosis of parapharyngeal neurilemmoma is frequently missed. Bimanual palpation of the mass is the most rewarding clinical investigation. Intra-oral incisional biopsy is to be prescribed in case of benign tumor. Treatment is achieved by total excision by external approach. Recurrence rates in benign lesions are low but high with malignant tumors. Three cases of parapharyngeal neurilemmoma are presented.", "contents": "Neurilemmoma of the parapharyngeal space. Report of three cases and review of the literature. The clinical pre-operative diagnosis of parapharyngeal neurilemmoma is frequently missed. Bimanual palpation of the mass is the most rewarding clinical investigation. Intra-oral incisional biopsy is to be prescribed in case of benign tumor. Treatment is achieved by total excision by external approach. Recurrence rates in benign lesions are low but high with malignant tumors. Three cases of parapharyngeal neurilemmoma are presented."}
{"id": "PMID:228050", "title": "Glycopeptides of murine leukemia viruses. I. Comparison of two ecotropic viruses.", "content": "The glycopeptides obtained by pronase digestion of two ecotropic strains of murine leukemia virus (MuLV) were compared by gel filtration. Four different glycopeptide size classes, designated G(1), G(2), G(3), and G(4), with molecular weights of approximately 5,100, 2,900, 2,200, and 1,500, respectively, were shown to be associated with Rauscher MuLV virions grown in JLS-V9 cells. Various sugar precursors, including glucosamine, galactose, fucose, and mannose were incorporated into G(1) and G(2), suggesting that these are complex (type I) glycopeptides. The two smaller glycopeptide size classes, G(3) and G(4), were shown to be mannoserich (type II) glycopeptides. G(4) was more sensitive to digestion with endo-beta-N-acetylglucosaminidase H than G(3), suggesting that the core of G(3) may contain fewer mannose residues. Glycopeptides of the same size class as G(1) and G(2) were associated with both Rauscher MuLV and AKR-MuLV grown in III6A (mouse embryo) cells. Previous studies have shown that gp52, a proteolytic cleavage product of gp70, possessed primarily G(1) glycopeptides and that gp52 was more highly sulfated than gp70. We observed that G(1) is approximately twofold more highly sulfated than G(2), explaining the observed difference in sulfation of gp52. The unusually large size of G(1) suggested that infection with MuLV may alter the host cell glycosylation pattern. To test this possibility, glycopeptides from Sindbis virions grown in uninfected and Rauscher MuLV-infected JLS-V9 cells were compared, and no differences were observed. G(1) was not detected in Sindbis virions, indicating that acquisition of G(1) depends on properties of the virus-coded polypeptide backbone of the gp70 molecule.", "contents": "Glycopeptides of murine leukemia viruses. I. Comparison of two ecotropic viruses. The glycopeptides obtained by pronase digestion of two ecotropic strains of murine leukemia virus (MuLV) were compared by gel filtration. Four different glycopeptide size classes, designated G(1), G(2), G(3), and G(4), with molecular weights of approximately 5,100, 2,900, 2,200, and 1,500, respectively, were shown to be associated with Rauscher MuLV virions grown in JLS-V9 cells. Various sugar precursors, including glucosamine, galactose, fucose, and mannose were incorporated into G(1) and G(2), suggesting that these are complex (type I) glycopeptides. The two smaller glycopeptide size classes, G(3) and G(4), were shown to be mannoserich (type II) glycopeptides. G(4) was more sensitive to digestion with endo-beta-N-acetylglucosaminidase H than G(3), suggesting that the core of G(3) may contain fewer mannose residues. Glycopeptides of the same size class as G(1) and G(2) were associated with both Rauscher MuLV and AKR-MuLV grown in III6A (mouse embryo) cells. Previous studies have shown that gp52, a proteolytic cleavage product of gp70, possessed primarily G(1) glycopeptides and that gp52 was more highly sulfated than gp70. We observed that G(1) is approximately twofold more highly sulfated than G(2), explaining the observed difference in sulfation of gp52. The unusually large size of G(1) suggested that infection with MuLV may alter the host cell glycosylation pattern. To test this possibility, glycopeptides from Sindbis virions grown in uninfected and Rauscher MuLV-infected JLS-V9 cells were compared, and no differences were observed. G(1) was not detected in Sindbis virions, indicating that acquisition of G(1) depends on properties of the virus-coded polypeptide backbone of the gp70 molecule."}
{"id": "PMID:228051", "title": "RNA synthesis of vesicular stomatitis virus-infected cells: in vivo regulation of replication.", "content": "Pulse-labeling of vesicular stomatitis virus-infected HeLa and BHK cells with [3H]uridine throughout the infectious cycle demonstrated two peaks of uridine incorporation into virus-specific RNA molecules. By separating total RNA synthesis into replication and transcription products, we showed that replication occurs over a shorter period of time in one peak synthesis. The biphasic nature of uridine incorporation is in part due to a general membrane phenomenon of reduced metabolite transport during vesicular stomatis virus infection and in part due to the apparent uncoupling of replication and transcription. A change in the ratio of newly synthesized plus and minus strands of the genome length (42S) RNA was found as the infection proceeded. Early in the infection, plus-stranded 42S RNA comprised 40% of the total genome length RNA synthesis, whereas late in infection, only 15 to 20% of the 42S RNA synthesized was complementary to the virion minus strand. Our data suggest that the rate of synthesis of plus-stranded 42S RNA was constant throughout the infection. The rate of virus release was determined by monitoring the uptake of [3H]uridine into released virus particles. Virus maturation and release are closely associated with the assembly of 42S RNA-containing nucleocapsids.", "contents": "RNA synthesis of vesicular stomatitis virus-infected cells: in vivo regulation of replication. Pulse-labeling of vesicular stomatitis virus-infected HeLa and BHK cells with [3H]uridine throughout the infectious cycle demonstrated two peaks of uridine incorporation into virus-specific RNA molecules. By separating total RNA synthesis into replication and transcription products, we showed that replication occurs over a shorter period of time in one peak synthesis. The biphasic nature of uridine incorporation is in part due to a general membrane phenomenon of reduced metabolite transport during vesicular stomatis virus infection and in part due to the apparent uncoupling of replication and transcription. A change in the ratio of newly synthesized plus and minus strands of the genome length (42S) RNA was found as the infection proceeded. Early in the infection, plus-stranded 42S RNA comprised 40% of the total genome length RNA synthesis, whereas late in infection, only 15 to 20% of the 42S RNA synthesized was complementary to the virion minus strand. Our data suggest that the rate of synthesis of plus-stranded 42S RNA was constant throughout the infection. The rate of virus release was determined by monitoring the uptake of [3H]uridine into released virus particles. Virus maturation and release are closely associated with the assembly of 42S RNA-containing nucleocapsids."}
{"id": "PMID:228052", "title": "Induction of thymidine kinase and DNase in varicella-zoster virus-infected cells and kinetic properties of the virus-induced thymidine kinase.", "content": "Thymidine kinase (TK), DNA polymerase, and DNase activities were induced in human foreskin fibroblasts after varicella-zoster virus infection. The induced TK and DNase activities have electrophoretic mobilities different from the corresponding host enzymes. Varicella-zoster virus-induced TK was purified and separated from the host enzyme by affinity column chromatography. This enzyme has been shown to have a broader substrate specificity with respect to either the phosphate donor or acceptor as compared with human cytoplasmic and mitochondrial TKs. The best phosphate donor is ATP, with a Km of 16 microM. The Km values of thymidine, deoxycytidine, and 5-propyl deoxyuridine were estimated to be 0.4, 180, and 0.8 microM, respectively. The Ki values for several analogs of thymidine such as 5-iododeoxyuridine, arabinofuranosylthymine, 5-ethyl deoxyuridine, and 5-cyanodeoxyuridine were also examined. TTP acted as a noncompetitive inhibitor with respect to thymidine with a Ki of 5 microM. The kinetic behavior of varicella-zoster virus-induced TK is different from human cytoplasmic, human mitochondrial, and herpes simplex virus type 1- and 2-induced TKs.", "contents": "Induction of thymidine kinase and DNase in varicella-zoster virus-infected cells and kinetic properties of the virus-induced thymidine kinase. Thymidine kinase (TK), DNA polymerase, and DNase activities were induced in human foreskin fibroblasts after varicella-zoster virus infection. The induced TK and DNase activities have electrophoretic mobilities different from the corresponding host enzymes. Varicella-zoster virus-induced TK was purified and separated from the host enzyme by affinity column chromatography. This enzyme has been shown to have a broader substrate specificity with respect to either the phosphate donor or acceptor as compared with human cytoplasmic and mitochondrial TKs. The best phosphate donor is ATP, with a Km of 16 microM. The Km values of thymidine, deoxycytidine, and 5-propyl deoxyuridine were estimated to be 0.4, 180, and 0.8 microM, respectively. The Ki values for several analogs of thymidine such as 5-iododeoxyuridine, arabinofuranosylthymine, 5-ethyl deoxyuridine, and 5-cyanodeoxyuridine were also examined. TTP acted as a noncompetitive inhibitor with respect to thymidine with a Ki of 5 microM. The kinetic behavior of varicella-zoster virus-induced TK is different from human cytoplasmic, human mitochondrial, and herpes simplex virus type 1- and 2-induced TKs."}
{"id": "PMID:228053", "title": "Guanidine-sensitive Na+ accumulation by poliovirus-infected HeLa cells.", "content": "The Na+ content of poliovirus-infected HeLa S3 cells increased during the late phase of virus replication, after virus inhibition of host cell protein synthesis and in coincidence with late viral functions. Guanidine hydrochloride blocked the rise in Na+ content, whereas the antiguanidine agent choline fully reversed the guanidine block. Expression of one or more late viral functions was essential for Na+ accumulation to occur because accumulation was inhibited by cycloheximide or guanidine added to the infected culture during the late phase. Increased adenosine triphosphatase activity appears to be primarily responsible for Na+ accumulation by virus-infected cells.", "contents": "Guanidine-sensitive Na+ accumulation by poliovirus-infected HeLa cells. The Na+ content of poliovirus-infected HeLa S3 cells increased during the late phase of virus replication, after virus inhibition of host cell protein synthesis and in coincidence with late viral functions. Guanidine hydrochloride blocked the rise in Na+ content, whereas the antiguanidine agent choline fully reversed the guanidine block. Expression of one or more late viral functions was essential for Na+ accumulation to occur because accumulation was inhibited by cycloheximide or guanidine added to the infected culture during the late phase. Increased adenosine triphosphatase activity appears to be primarily responsible for Na+ accumulation by virus-infected cells."}
{"id": "PMID:228054", "title": "Intracellular forms of simian virus 40 nucleoprotein complexes. II. Biochemical and electron microscopic analysis of simian virus 40 virion assembly.", "content": "The simian virus 40 virion assembly process was studied with pulse-labeling kinetics of virion proteins, CsCl gradient analysis, electron microscopy, and low-salt gel electrophoresis. The results obtained are consistent with the model of gradual addition and organization of capsid proteins around simian virus 40 chromatin. Empty virions, as observed in the CsCl gradient by previous workers, were found to be the dissociation product of immature virus. Histone H1 was found in simian virus 40 chromatin and virion assembly intermediates but not in the mature virion banding at 1.34 g/ml in the CsCl gradient.", "contents": "Intracellular forms of simian virus 40 nucleoprotein complexes. II. Biochemical and electron microscopic analysis of simian virus 40 virion assembly. The simian virus 40 virion assembly process was studied with pulse-labeling kinetics of virion proteins, CsCl gradient analysis, electron microscopy, and low-salt gel electrophoresis. The results obtained are consistent with the model of gradual addition and organization of capsid proteins around simian virus 40 chromatin. Empty virions, as observed in the CsCl gradient by previous workers, were found to be the dissociation product of immature virus. Histone H1 was found in simian virus 40 chromatin and virion assembly intermediates but not in the mature virion banding at 1.34 g/ml in the CsCl gradient."}
{"id": "PMID:228055", "title": "DNA of human cytomegalovirus: size heterogeneity and defectiveness resulting from serial undiluted passage.", "content": "The majority of DNA molecules associated with plaque-purified, low-multiplicity-passaged human cytomegalovirus (Towne strain) had a molecular weight of approximately 150 x 10(6) and a molecular complexity of approximately 140 x 10(6). Serial high-multiplicity passage resulted in the production of defective cytomegalovirions. An accumulation of smaller DNA molecules packaged into virions was directly correlated with a decrease in infectivity and an increase in the particle-to-PFU ratio. The majority of defective DNA molecules had a molecular weight of approximately 100 x 10(6). In addition, there were some viral DNA molecules of approximately 60 x 10(6). Restriction enzyme analysis of defective cytomegalovirus DNA detected unique DNA fragments, suggesting a specific alteration in the nucleotide sequence. Some reasons for the generation of defective cytomegalovirus DNA are discussed.", "contents": "DNA of human cytomegalovirus: size heterogeneity and defectiveness resulting from serial undiluted passage. The majority of DNA molecules associated with plaque-purified, low-multiplicity-passaged human cytomegalovirus (Towne strain) had a molecular weight of approximately 150 x 10(6) and a molecular complexity of approximately 140 x 10(6). Serial high-multiplicity passage resulted in the production of defective cytomegalovirions. An accumulation of smaller DNA molecules packaged into virions was directly correlated with a decrease in infectivity and an increase in the particle-to-PFU ratio. The majority of defective DNA molecules had a molecular weight of approximately 100 x 10(6). In addition, there were some viral DNA molecules of approximately 60 x 10(6). Restriction enzyme analysis of defective cytomegalovirus DNA detected unique DNA fragments, suggesting a specific alteration in the nucleotide sequence. Some reasons for the generation of defective cytomegalovirus DNA are discussed."}
{"id": "PMID:228056", "title": "Characterization of visna virus mRNA.", "content": "Visna virus is a retrovirus responsible for a classical slow infection of the central nervous system of sheep. In the present work we focused our attention on the viral mRNA's. We found that, during the acute infection in vitro, (i) viral mRNA's amount to only 0.1% of the total cytoplasmic RNA, (ii) 20% of the total cytoplasmic viral RNA is found in polyribosomes, and (iii) three viral mRNA's can be identified by sucrose gradient sedimentation or polyacrylamide gel electrophoresis. Their sedimentation coefficients are 36S, 27S, and 21S.", "contents": "Characterization of visna virus mRNA. Visna virus is a retrovirus responsible for a classical slow infection of the central nervous system of sheep. In the present work we focused our attention on the viral mRNA's. We found that, during the acute infection in vitro, (i) viral mRNA's amount to only 0.1% of the total cytoplasmic RNA, (ii) 20% of the total cytoplasmic viral RNA is found in polyribosomes, and (iii) three viral mRNA's can be identified by sucrose gradient sedimentation or polyacrylamide gel electrophoresis. Their sedimentation coefficients are 36S, 27S, and 21S."}
{"id": "PMID:228057", "title": "High-frequency recombination within the gag gene of Rous sarcoma virus.", "content": "We isolated 28 recombinants of Rous sarcoma virus at early (24 h) and late (7 days) times after infection. These recombinants were selected for wild type in the pol and src genes and analyzed for their env and gag phenotypes. We were unable to show strong linkage between any two markers, including two markers within a single gene (gag).", "contents": "High-frequency recombination within the gag gene of Rous sarcoma virus. We isolated 28 recombinants of Rous sarcoma virus at early (24 h) and late (7 days) times after infection. These recombinants were selected for wild type in the pol and src genes and analyzed for their env and gag phenotypes. We were unable to show strong linkage between any two markers, including two markers within a single gene (gag)."}
{"id": "PMID:228058", "title": "Separation and characterization of herpes simplex virus type 1 immediate-early mRNA's.", "content": "Polyadenylated immediate-early transcripts of herpes simplex virus type 1, made in BHK cells infected and maintained in the presence of cycloheximide, have been separated on denaturing agarose gels containing methyl mercuric hydroxide. Three virus-specific mRNA bands of estimated sizes 4.7, 3.0, and 2.0 kilobases (kb) were detected, and these mRNA's were mapped on the virus genome and also used to direct protein synthesis in vitro. The 4.7- and 3.0-kb mRNA's hybridized predominantly to certain DNA fragments which are located in the short and long repetitive regions of the genome, respectively, whereas the 2.0-kb mRNA's mapped to three discrete regions of the virus DNA. In vitro translation of these separated mRNA size classes indicated that the 3.0-kb mRNA specified the synthesis of virus polypeptide Vmw 110, whereas the 2.0-kb mRNA's specified Vmw 68, 63, and 12. The synthesis of small amounts of Vmw 175 was specified by the 4.7-kb mRNA. In contrast with the mRNA's which specify these other immediate-early polypeptides, that specifying Vmw 12 is much larger than required for its coding sequences.", "contents": "Separation and characterization of herpes simplex virus type 1 immediate-early mRNA's. Polyadenylated immediate-early transcripts of herpes simplex virus type 1, made in BHK cells infected and maintained in the presence of cycloheximide, have been separated on denaturing agarose gels containing methyl mercuric hydroxide. Three virus-specific mRNA bands of estimated sizes 4.7, 3.0, and 2.0 kilobases (kb) were detected, and these mRNA's were mapped on the virus genome and also used to direct protein synthesis in vitro. The 4.7- and 3.0-kb mRNA's hybridized predominantly to certain DNA fragments which are located in the short and long repetitive regions of the genome, respectively, whereas the 2.0-kb mRNA's mapped to three discrete regions of the virus DNA. In vitro translation of these separated mRNA size classes indicated that the 3.0-kb mRNA specified the synthesis of virus polypeptide Vmw 110, whereas the 2.0-kb mRNA's specified Vmw 68, 63, and 12. The synthesis of small amounts of Vmw 175 was specified by the 4.7-kb mRNA. In contrast with the mRNA's which specify these other immediate-early polypeptides, that specifying Vmw 12 is much larger than required for its coding sequences."}
{"id": "PMID:228059", "title": "Diversity of mammary tumor viral genes within the genus Mus, the species Mus musculus, and the strain C3H.", "content": "Proviral sequences complementary to the C3H mouse mammary tumor virus RNA genome are present in the DNA of early occurring mammary tumors of C3H/HeN mice and are absent from apparently normal C3H/HeN tissues; these sequences are non-germ line transmitted in C3H/HeN mice and have been termed tumor-associated sequences; (W. Drohan et al., J. Virol. 21:986-995, 1977). We report here that tumor-associated sequences are present in the DNA of spontaneous mammary tumors that occur early in the life of several inbred, high-tumor-incidence mouse strains but are absent in mammary tumors that occur later in life in low- and moderate-tumor-incidence strains. These sequences are also absent in apparently normal organs tested from numerous laboratory mouse strains, feral mice, Mus musculus subspecies, and other Mus species. Sequences represented in tumor-associated sequence RNA, however, are present as endogenous provirus in GR mice (at approximately four copies per haploid genome) and in two of five substrains of C3H mice tested (at approximately one copy per haploid genome). The two substrains of C3H mice positive for endogenous tumor-associated sequence provirus were recently (circa 1930) separated from the negative substrains of C3H mice. The results may be explained by the unlikely chance segregation of proviral sequences or by the recent integration of viral genes (within the last few decades). Whereas radioactively labeled mouse mammary tumor virus 60-70S RNA or complementary DNA detected mouse mammary tumor virus-related proviral information in all laboratory mouse strains, feral mice, subspecies of M. musculus, and other species of Mus, the use of tumor-associated sequence RNA clearly revealed the genetic diversity that may exist between different colonies or substrains of \"inbred\" laboratory mice commonly used in cancer research.", "contents": "Diversity of mammary tumor viral genes within the genus Mus, the species Mus musculus, and the strain C3H. Proviral sequences complementary to the C3H mouse mammary tumor virus RNA genome are present in the DNA of early occurring mammary tumors of C3H/HeN mice and are absent from apparently normal C3H/HeN tissues; these sequences are non-germ line transmitted in C3H/HeN mice and have been termed tumor-associated sequences; (W. Drohan et al., J. Virol. 21:986-995, 1977). We report here that tumor-associated sequences are present in the DNA of spontaneous mammary tumors that occur early in the life of several inbred, high-tumor-incidence mouse strains but are absent in mammary tumors that occur later in life in low- and moderate-tumor-incidence strains. These sequences are also absent in apparently normal organs tested from numerous laboratory mouse strains, feral mice, Mus musculus subspecies, and other Mus species. Sequences represented in tumor-associated sequence RNA, however, are present as endogenous provirus in GR mice (at approximately four copies per haploid genome) and in two of five substrains of C3H mice tested (at approximately one copy per haploid genome). The two substrains of C3H mice positive for endogenous tumor-associated sequence provirus were recently (circa 1930) separated from the negative substrains of C3H mice. The results may be explained by the unlikely chance segregation of proviral sequences or by the recent integration of viral genes (within the last few decades). Whereas radioactively labeled mouse mammary tumor virus 60-70S RNA or complementary DNA detected mouse mammary tumor virus-related proviral information in all laboratory mouse strains, feral mice, subspecies of M. musculus, and other species of Mus, the use of tumor-associated sequence RNA clearly revealed the genetic diversity that may exist between different colonies or substrains of \"inbred\" laboratory mice commonly used in cancer research."}
{"id": "PMID:228060", "title": "Induction of mouse mammary tumor virus RNA in mammary tumors of BALB/c mice treated with urethane, X-irradiation, and hormones.", "content": "The involvement of mouse mammary tumor virus (MTV) in the development of mammary tumors of nonviral etiology in BALB/c mice was studied by measuring the levels of MTV RNA, MTV DNA, and MTV proteins in spontaneously arising and hormonally, chemically, and/or physically induced mammary tumors of BALB/c females. The following results were obtained. (i) Spontaneous mammary tumors contained very low levels of MTV RNA; 4 X 10(-6)% of the the cytoplasmic RNA was MTV RNA. No MTV proteins could be demonstrated by using sensitive radioimmunoassays for MTV proteins p27 and gp52. (ii) Mammary tumors induced by treatments with urethane or X-irradiation alone contained higher levels of MTV RNA; these tumors contained 3- and 19-fold more MTV RNA, respectively, compared with spontaneous mammary tumors. (iii) Mammary tumors induced by combined treatment with urethane and X-irradiation expressed high levels of MTV RNA in the mammary tumors; a 1,724-fold increase in MTV RNA content compared with spontaneous mammary tumors was observed. However, very low levels of MTV proteins gp52 and p27 were detected, suggesting some kind of impairment at the translation of the MTV RNA. MTV RNA was also induced by this treatment in mammary glands and spleens, but not in the livers of tumor-bearing animals. (iv) Balb/c females continuously exposed to prolactin contained high levels of MTV RNA and MTV proteins in stimulated mammary glands and in the hormonally induced mammary tumors. These findings suggest that MTV is not responsible for the maintenance and probably also not for the development of all murine mammary cancers.", "contents": "Induction of mouse mammary tumor virus RNA in mammary tumors of BALB/c mice treated with urethane, X-irradiation, and hormones. The involvement of mouse mammary tumor virus (MTV) in the development of mammary tumors of nonviral etiology in BALB/c mice was studied by measuring the levels of MTV RNA, MTV DNA, and MTV proteins in spontaneously arising and hormonally, chemically, and/or physically induced mammary tumors of BALB/c females. The following results were obtained. (i) Spontaneous mammary tumors contained very low levels of MTV RNA; 4 X 10(-6)% of the the cytoplasmic RNA was MTV RNA. No MTV proteins could be demonstrated by using sensitive radioimmunoassays for MTV proteins p27 and gp52. (ii) Mammary tumors induced by treatments with urethane or X-irradiation alone contained higher levels of MTV RNA; these tumors contained 3- and 19-fold more MTV RNA, respectively, compared with spontaneous mammary tumors. (iii) Mammary tumors induced by combined treatment with urethane and X-irradiation expressed high levels of MTV RNA in the mammary tumors; a 1,724-fold increase in MTV RNA content compared with spontaneous mammary tumors was observed. However, very low levels of MTV proteins gp52 and p27 were detected, suggesting some kind of impairment at the translation of the MTV RNA. MTV RNA was also induced by this treatment in mammary glands and spleens, but not in the livers of tumor-bearing animals. (iv) Balb/c females continuously exposed to prolactin contained high levels of MTV RNA and MTV proteins in stimulated mammary glands and in the hormonally induced mammary tumors. These findings suggest that MTV is not responsible for the maintenance and probably also not for the development of all murine mammary cancers."}
{"id": "PMID:228061", "title": "Proposed replicative role of the NS polypeptide of vesicular stomatitis virus: structural analysis of an electrophoretic variant.", "content": "The structural lesion in the temperature-sensitive mutant E1 of the New Jersey serotype of vesicular stomatitis virus has been assigned to the NS protein. Although the packaged wild-type and mutant NS proteins were similarly phosphorylated, the mutant NS protein migrated faster than the wild-type NS protein in polyacrylamide slab gels electrophoresed in the presence of sodium dodecyl sulfate. The resolution appears to be the result of conformational rather than size differences since the two proteins comigrated in polyacrylamide gels which contained 4 M urea in addition to sodium dodecyl sulfate. Peptide maps, obtained by limited proteolysis of 32P-labeled wild-type and mutant NS proteins with Staphylococcus aureus V8 protease and papain, revealed striking differences which suggested that the mutant alteration could involve an aspartic or glutamic acid residue. Since NS proteins obtained from naturally occurring revertants of E1 were indistinguishable from the wild-type protein in all of these analyses, the structural alteration in the mutant NS protein correlates with the functional lesion. Because E1 is defective in the RNA replication pathway at the restrictive temperature, a replicative role is proposed for the NS protein.", "contents": "Proposed replicative role of the NS polypeptide of vesicular stomatitis virus: structural analysis of an electrophoretic variant. The structural lesion in the temperature-sensitive mutant E1 of the New Jersey serotype of vesicular stomatitis virus has been assigned to the NS protein. Although the packaged wild-type and mutant NS proteins were similarly phosphorylated, the mutant NS protein migrated faster than the wild-type NS protein in polyacrylamide slab gels electrophoresed in the presence of sodium dodecyl sulfate. The resolution appears to be the result of conformational rather than size differences since the two proteins comigrated in polyacrylamide gels which contained 4 M urea in addition to sodium dodecyl sulfate. Peptide maps, obtained by limited proteolysis of 32P-labeled wild-type and mutant NS proteins with Staphylococcus aureus V8 protease and papain, revealed striking differences which suggested that the mutant alteration could involve an aspartic or glutamic acid residue. Since NS proteins obtained from naturally occurring revertants of E1 were indistinguishable from the wild-type protein in all of these analyses, the structural alteration in the mutant NS protein correlates with the functional lesion. Because E1 is defective in the RNA replication pathway at the restrictive temperature, a replicative role is proposed for the NS protein."}
{"id": "PMID:228062", "title": "New procedure for isolation of Rous sarcoma virus-specific RNA from infected cells.", "content": "The use of mercurated \"strong stop\" complementary DNA (complementary to the 5'-terminal 101 nucleotides of Rous sarcoma virus RNA) in the isolation of virus-specific RNA from infected chicken embryo fibroblasts is described. Strong stop Rous sarcoma virus complementary DNA was mercurated chemically, and, as a result of the low complexity of this DNA, short hybridization times (up to 15 min) and heating in the absence of formamide were found to be adequate conditions for the isolation of virus-specific RNA. The purity of the isolated RNA was demonstrated by analysis of labeled RNase T1-resistant oligonucleotides by two-dimensional polyacrylamide gel electrophoresis. The isolated RNA could be translated in the in vitro protein synthesis system derived from rabbit reticulocytes, and an analysis of polypeptides programmed by isolated RNA before and after immunoprecipitation further demonstrated both the purity of the isolated mRNA and the quantitative nature of the isolation procedure.", "contents": "New procedure for isolation of Rous sarcoma virus-specific RNA from infected cells. The use of mercurated \"strong stop\" complementary DNA (complementary to the 5'-terminal 101 nucleotides of Rous sarcoma virus RNA) in the isolation of virus-specific RNA from infected chicken embryo fibroblasts is described. Strong stop Rous sarcoma virus complementary DNA was mercurated chemically, and, as a result of the low complexity of this DNA, short hybridization times (up to 15 min) and heating in the absence of formamide were found to be adequate conditions for the isolation of virus-specific RNA. The purity of the isolated RNA was demonstrated by analysis of labeled RNase T1-resistant oligonucleotides by two-dimensional polyacrylamide gel electrophoresis. The isolated RNA could be translated in the in vitro protein synthesis system derived from rabbit reticulocytes, and an analysis of polypeptides programmed by isolated RNA before and after immunoprecipitation further demonstrated both the purity of the isolated mRNA and the quantitative nature of the isolation procedure."}
{"id": "PMID:228063", "title": "Abnormal properties of an immediate early polypeptide in cells infected with the herpes simplex virus type 1 mutant tsK.", "content": "Previous studies (R. J. Watson and J. B. Clements, Virology 91:364--379, 1978; C. M. Preston, J. Virol. 29:275--284, 1979) have shown that the herpes simplex virus type 1 (HSV-1) mutant tsK has a temperature-sensitive lesion in an immediate early polypeptide whose function is to induce synthesis of new viral transcripts, including mRNA, for pyrimidine deoxyribonucleoside kinase. The studies presented here examine the properties of immediate early polypeptides in wild-type HSV-1 and tsK-infected cells at 31 and 38.5 degrees C. The overall pattern of immediate early protein synthesis was similar in wild-type HSV-1- and tsK-infected cells when radiolabeled with [35S]methionine or 14C-amino acid mixture. Further investigation, however, revealed two aberrant properties of the polypeptide Vmw 175 in tsK-infected cells at 38.5 degrees C. Upon cell fractionation, large amounts of this polypeptide were recovered in the cytoplasmic fraction, in contrast to tsK-infected cells at 31 degrees C or wild-type HSV-1-infected cells at either temperature. Furthermore, at 38.5 degrees C tsK-induced Vmw 175 was not processed normally to forms of lower electrophoretic mobility. Both of these defects were reversible upon downshift of tsK-infected cells, even in the absence of further protein synthesis, but were not observed in cells infected with a revertant of tsK. Coinfection of tsK-infected cells with wild-type HSV-1 did not alleviate these lesions, suggesting that they resulted from an abnormal Vmw 175 polypeptide rather than from a defective processing enzyme. Temperature upshift of tsK-infected cells caused reversion of Vmw 175 to the mutant form. The progression to synthesis of late polypeptides was also arrested; therefore, a functional lesion was also reversible upon temperature changes between 31 and 38.5 degrees C during the early stages of infection. The identification of a polypeptide with abnormal properties in tsK-infected cells and the demonstration that these properties, and the functional lesion, are reversible may provide an important system for investigation of HSV-1 transcriptional control.", "contents": "Abnormal properties of an immediate early polypeptide in cells infected with the herpes simplex virus type 1 mutant tsK. Previous studies (R. J. Watson and J. B. Clements, Virology 91:364--379, 1978; C. M. Preston, J. Virol. 29:275--284, 1979) have shown that the herpes simplex virus type 1 (HSV-1) mutant tsK has a temperature-sensitive lesion in an immediate early polypeptide whose function is to induce synthesis of new viral transcripts, including mRNA, for pyrimidine deoxyribonucleoside kinase. The studies presented here examine the properties of immediate early polypeptides in wild-type HSV-1 and tsK-infected cells at 31 and 38.5 degrees C. The overall pattern of immediate early protein synthesis was similar in wild-type HSV-1- and tsK-infected cells when radiolabeled with [35S]methionine or 14C-amino acid mixture. Further investigation, however, revealed two aberrant properties of the polypeptide Vmw 175 in tsK-infected cells at 38.5 degrees C. Upon cell fractionation, large amounts of this polypeptide were recovered in the cytoplasmic fraction, in contrast to tsK-infected cells at 31 degrees C or wild-type HSV-1-infected cells at either temperature. Furthermore, at 38.5 degrees C tsK-induced Vmw 175 was not processed normally to forms of lower electrophoretic mobility. Both of these defects were reversible upon downshift of tsK-infected cells, even in the absence of further protein synthesis, but were not observed in cells infected with a revertant of tsK. Coinfection of tsK-infected cells with wild-type HSV-1 did not alleviate these lesions, suggesting that they resulted from an abnormal Vmw 175 polypeptide rather than from a defective processing enzyme. Temperature upshift of tsK-infected cells caused reversion of Vmw 175 to the mutant form. The progression to synthesis of late polypeptides was also arrested; therefore, a functional lesion was also reversible upon temperature changes between 31 and 38.5 degrees C during the early stages of infection. The identification of a polypeptide with abnormal properties in tsK-infected cells and the demonstration that these properties, and the functional lesion, are reversible may provide an important system for investigation of HSV-1 transcriptional control."}
{"id": "PMID:228064", "title": "Replication of polyoma DNA in isolated nuclei: analysis of replication fork movement.", "content": "The movement of replication forks during polyoma DNA synthesis in isolated nuclei was analyzed by digesting newly synthesized DNA with the restriction endonuclease HpaII which cleaves polyoma DNA into eight unique fragments. The terminus of in vitro DNA synthesis was identified by cleaving newly completed molecules with HpaII. The distribution of label in the restriction fragments showed that the in vitro DNA synthesis was bidirectional and had the normal terminus of replication. Analysis of replicative intermediates pulse-labeled in vitro further suggested that DNA synthesis in isolated nuclei is an ordered process similar to replication in intact cells. Replication forks moved with a constant rate from the origin towards the terminus of replication. The nonlinear course of the DNA synthesis reaction in the isolated nuclei seems to result from the random inactivation of replication forks rather than a decrease in the rate of fork movement. During the in vitro synthesis a replication fork could maximally synthesize a DNA chain about 1,000 nucleotides long. The results suggest that some replication forks might be initiated in vitro at the origin of replication.", "contents": "Replication of polyoma DNA in isolated nuclei: analysis of replication fork movement. The movement of replication forks during polyoma DNA synthesis in isolated nuclei was analyzed by digesting newly synthesized DNA with the restriction endonuclease HpaII which cleaves polyoma DNA into eight unique fragments. The terminus of in vitro DNA synthesis was identified by cleaving newly completed molecules with HpaII. The distribution of label in the restriction fragments showed that the in vitro DNA synthesis was bidirectional and had the normal terminus of replication. Analysis of replicative intermediates pulse-labeled in vitro further suggested that DNA synthesis in isolated nuclei is an ordered process similar to replication in intact cells. Replication forks moved with a constant rate from the origin towards the terminus of replication. The nonlinear course of the DNA synthesis reaction in the isolated nuclei seems to result from the random inactivation of replication forks rather than a decrease in the rate of fork movement. During the in vitro synthesis a replication fork could maximally synthesize a DNA chain about 1,000 nucleotides long. The results suggest that some replication forks might be initiated in vitro at the origin of replication."}
{"id": "PMID:228065", "title": "Nucleotide sequences from the 3'-ends of vesicular stomatitis virus mRNA's as determined from cloned DNA.", "content": "Molecular clones of vesicular stomatitis virus mRNA's were used to determine the 3'-terminal sequences of mRNA's encoding the N and NS proteins. This new approach to VSV mRNA sequencing allowed the first comparison of 3'-terminal sequences. The sequences showed a tetranucleotide homology, UAUG, immediately preceding the polyadenylic acid. In addition, both mRNA's had an AU-rich region including the tetranucleotide AUAU at positions 16 to 19 nucleotides from the polyadenylic acid. A possible secondary structure between the 3' end of N mRNA and the 5' end of the adjacent NS mRNA is noted. These structural features may serve as signals for termination (or cleavage) and polyadenylation of vesicular stomatitis virus mRNA's. Neither mRNA had the polyadenylic acidproximal hexanucleotide, AAUAAA, found in eucaryotic cellular and viral mRNA's transcribed from nuclear DNA. The probable location of the translation termination codon for the NS protein is only six nucleotides from polyadenylic acid in NS mRNA.", "contents": "Nucleotide sequences from the 3'-ends of vesicular stomatitis virus mRNA's as determined from cloned DNA. Molecular clones of vesicular stomatitis virus mRNA's were used to determine the 3'-terminal sequences of mRNA's encoding the N and NS proteins. This new approach to VSV mRNA sequencing allowed the first comparison of 3'-terminal sequences. The sequences showed a tetranucleotide homology, UAUG, immediately preceding the polyadenylic acid. In addition, both mRNA's had an AU-rich region including the tetranucleotide AUAU at positions 16 to 19 nucleotides from the polyadenylic acid. A possible secondary structure between the 3' end of N mRNA and the 5' end of the adjacent NS mRNA is noted. These structural features may serve as signals for termination (or cleavage) and polyadenylation of vesicular stomatitis virus mRNA's. Neither mRNA had the polyadenylic acidproximal hexanucleotide, AAUAAA, found in eucaryotic cellular and viral mRNA's transcribed from nuclear DNA. The probable location of the translation termination codon for the NS protein is only six nucleotides from polyadenylic acid in NS mRNA."}
{"id": "PMID:228066", "title": "Inhibition of Rous sarcoma virus replication by 2-deoxyglucose and tunicamycin: identification of an unglycosylated env gene product.", "content": "Two inhibitors of glycosylation, 2-deoxyglucose and tunicamycin, depressed the synthesis of infectious Rous sarcoma virus greater than 100-fold. Under the same conditions only a two- to threefold decrease in the production of virus particles was observed. The noninfectious particles had a lower density (1.145 g/ml) in isopycnic sucrose gradients and lacked the two virion glycoproteins, gp85 and gp37, found on infectious virions. The four internal structural proteins of the virus, p27, p19, p15, and p12, appeared to be assembled normally into the noninfectious virus. Polypeptides related to the Rous sarcoma virus glycoproteins were immunoprecipitated from pulse-labeled Rous sarcoma virus (Prague strain, subgroup B)-transformed cells. pr95gp, the polyprotein precursor to gp85 and gp37, was the major protein precipitated from untreated cells. PR95GP, THE POLYPROTEIN PRECURSOR TO GP85 AND GP37, WAS THE MAJOR PROTEIN PRECIPITATED FROM UNTREATED CELLS. This was absent in both tunicamycin- and 2-deoxyglucose-treatec ells, and a new polypeptide of molecular weight 57,000 to 58,000 was the major species precipitated. In tunicamycin-treated cells this product was unstable and was degraded during a 2-h chase; in 2-deoxyglucose-treated cells, on the other hand, the polypeptide appeared to be more stable and underwent partial glycosylation. The synthesis and processing of pr76, the polyprotein precursor to the internal structural proteins of the virion, occurred normally in both treated and untreated cells. It is concluded that the unglycosylated env gene product is a polypeptide of molecular weight 57,000 to 58,000.", "contents": "Inhibition of Rous sarcoma virus replication by 2-deoxyglucose and tunicamycin: identification of an unglycosylated env gene product. Two inhibitors of glycosylation, 2-deoxyglucose and tunicamycin, depressed the synthesis of infectious Rous sarcoma virus greater than 100-fold. Under the same conditions only a two- to threefold decrease in the production of virus particles was observed. The noninfectious particles had a lower density (1.145 g/ml) in isopycnic sucrose gradients and lacked the two virion glycoproteins, gp85 and gp37, found on infectious virions. The four internal structural proteins of the virus, p27, p19, p15, and p12, appeared to be assembled normally into the noninfectious virus. Polypeptides related to the Rous sarcoma virus glycoproteins were immunoprecipitated from pulse-labeled Rous sarcoma virus (Prague strain, subgroup B)-transformed cells. pr95gp, the polyprotein precursor to gp85 and gp37, was the major protein precipitated from untreated cells. PR95GP, THE POLYPROTEIN PRECURSOR TO GP85 AND GP37, WAS THE MAJOR PROTEIN PRECIPITATED FROM UNTREATED CELLS. This was absent in both tunicamycin- and 2-deoxyglucose-treatec ells, and a new polypeptide of molecular weight 57,000 to 58,000 was the major species precipitated. In tunicamycin-treated cells this product was unstable and was degraded during a 2-h chase; in 2-deoxyglucose-treated cells, on the other hand, the polypeptide appeared to be more stable and underwent partial glycosylation. The synthesis and processing of pr76, the polyprotein precursor to the internal structural proteins of the virion, occurred normally in both treated and untreated cells. It is concluded that the unglycosylated env gene product is a polypeptide of molecular weight 57,000 to 58,000."}
{"id": "PMID:228067", "title": "Persistent vesicular stomatitis virus infection mediates base substitutions in viral RNA termini.", "content": "We have sequenced (via a product RNA) the 3' RNA terminus of a defective interfering particle that was generated from the standard virus isolated from a culture of BHK-21 cells persistently infected with vesicular stomatitis virus for over 5 years. By hybridization and RNA sequencing, seven mutations were identified in the 46 nucleotides at the terminus of this defective-interfering-particle RNA. It is likely that these mutations are a reflection of altered protein-nucleic acid interactions that the virus has evolved to maintain its persistently infected carrier state in vitro.", "contents": "Persistent vesicular stomatitis virus infection mediates base substitutions in viral RNA termini. We have sequenced (via a product RNA) the 3' RNA terminus of a defective interfering particle that was generated from the standard virus isolated from a culture of BHK-21 cells persistently infected with vesicular stomatitis virus for over 5 years. By hybridization and RNA sequencing, seven mutations were identified in the 46 nucleotides at the terminus of this defective-interfering-particle RNA. It is likely that these mutations are a reflection of altered protein-nucleic acid interactions that the virus has evolved to maintain its persistently infected carrier state in vitro."}
{"id": "PMID:228068", "title": "BamI, KpnI, and SalI restriction enzyme maps of the DNAs of herpes simplex virus strains Justin and F: occurrence of heterogeneities in defined regions of the viral DNA.", "content": "We present the locations of the cleavage sites for the BamI, KpnI, and SalI restriction endonucleases within the DNA molecules of herpes simplex virus type 1 (HSV-1) strains Justin and F. These restriction enzymes cleave the HSV-1 DNA at many sites, producing relatively small fragments which should prove useful in future studies of HSV-1 gene structure and function. The mapping data revealed the occurrence of heterogeneity within three regions of the viral genome including (i) the region spanning map coordinates 0.74--0.76, (ii) the ends of the large (L) DNA component, and (iii) the junction between the large (L) and the small (S) components. The heterogeneity in the ends of L and the S-L junctions of HSV-1 (Justin) and HSV-1 (F) DNAs was grossly similar to that previously reported to occur in the ends of L and the S-L junctions of the HSV-1 (KOS) DNA (M. J. Wagner and W. C. Summers, J. Virol. 27:374--387, 1978). Thus, cleavage of these regions with restriction endonucleases yielded sets of minor fragments differing in size by constant increments. However, the various strains of HSV-1 differed with respect to the numbers, size increments, and relative molarities of the various minor fragments, suggesting that the parameters of the heterogeneity are inherited in the structural makeup of the HSV-1 genome. The strain dependence of the pattern of heterogeneity can be most easily explained in terms of variable sizes of the terminally reiterated a sequence, contained in the DNA molecules of these three strains of HSV-1.", "contents": "BamI, KpnI, and SalI restriction enzyme maps of the DNAs of herpes simplex virus strains Justin and F: occurrence of heterogeneities in defined regions of the viral DNA. We present the locations of the cleavage sites for the BamI, KpnI, and SalI restriction endonucleases within the DNA molecules of herpes simplex virus type 1 (HSV-1) strains Justin and F. These restriction enzymes cleave the HSV-1 DNA at many sites, producing relatively small fragments which should prove useful in future studies of HSV-1 gene structure and function. The mapping data revealed the occurrence of heterogeneity within three regions of the viral genome including (i) the region spanning map coordinates 0.74--0.76, (ii) the ends of the large (L) DNA component, and (iii) the junction between the large (L) and the small (S) components. The heterogeneity in the ends of L and the S-L junctions of HSV-1 (Justin) and HSV-1 (F) DNAs was grossly similar to that previously reported to occur in the ends of L and the S-L junctions of the HSV-1 (KOS) DNA (M. J. Wagner and W. C. Summers, J. Virol. 27:374--387, 1978). Thus, cleavage of these regions with restriction endonucleases yielded sets of minor fragments differing in size by constant increments. However, the various strains of HSV-1 differed with respect to the numbers, size increments, and relative molarities of the various minor fragments, suggesting that the parameters of the heterogeneity are inherited in the structural makeup of the HSV-1 genome. The strain dependence of the pattern of heterogeneity can be most easily explained in terms of variable sizes of the terminally reiterated a sequence, contained in the DNA molecules of these three strains of HSV-1."}
{"id": "PMID:228069", "title": "DNase induced after infection of KB cells by herpes simplex virus type 1 or type 2. II. Characterization of an associated endonuclease activity.", "content": "Purified preparations of the \"exonuclease\" specified by herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) possess an endonuclease activity. The exonuclease and endonuclease activities copurify and cosediment in a sucrose density gradient. Endonuclease activity is only observed in the presence of a divalent cation, and Mg(2+) or Mn(2+) is equally effective as a cofactor with an optimal concentration of 2 mM. A slight amount of endonuclease activity is observed in the presence of Ca(2+), whereas no activity occurs in the presence of Zn(2+). In the presence of Mg(2+), Ca(2+) and Zn(2+) are inhibitory. Comparison of exonuclease and endonuclease activity in the presence of various divalent cations revealed that, at concentrations of Mn(2+) greater than 1 mM, only endonuclease activity occurs whereas endonuclease and exonuclease activity occur at all concentrations of Mg(2+). The endonuclease was affected by putrescine and spermidine to the same extent as the exonuclease activity, but in marked contrast the endonuclease was inhibited by a 10-fold-lower concentration of spermine compared to the exonuclease. The activity specified by HSV-1 and HSV-2 has very similar properties. HSV-1 and HSV-2 endonuclease cleave covalently closed circular DNA to yield, firstly, nicked circles and then linear DNA which is subsequently hydrolyzed to small oligonucleotides. Cleavage does not appear to be base sequence specific. Conversion of nicked circles to linear DNA and subsequent degradation of linear DNA occurs more rapidly in the presence of Mg(2+) than Mn(2+) presumably by virtue of the presence of the exonuclease activity. Nonsuperhelical covalently closed circular duplex DNA is cleaved by the endonucleases at a rate 60 times slower than the rate observed on the supercoiled form. These data indicate that the HSV-1 and HSV-2 endonuclease preferentially recognize single-stranded DNA regions.", "contents": "DNase induced after infection of KB cells by herpes simplex virus type 1 or type 2. II. Characterization of an associated endonuclease activity. Purified preparations of the \"exonuclease\" specified by herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) possess an endonuclease activity. The exonuclease and endonuclease activities copurify and cosediment in a sucrose density gradient. Endonuclease activity is only observed in the presence of a divalent cation, and Mg(2+) or Mn(2+) is equally effective as a cofactor with an optimal concentration of 2 mM. A slight amount of endonuclease activity is observed in the presence of Ca(2+), whereas no activity occurs in the presence of Zn(2+). In the presence of Mg(2+), Ca(2+) and Zn(2+) are inhibitory. Comparison of exonuclease and endonuclease activity in the presence of various divalent cations revealed that, at concentrations of Mn(2+) greater than 1 mM, only endonuclease activity occurs whereas endonuclease and exonuclease activity occur at all concentrations of Mg(2+). The endonuclease was affected by putrescine and spermidine to the same extent as the exonuclease activity, but in marked contrast the endonuclease was inhibited by a 10-fold-lower concentration of spermine compared to the exonuclease. The activity specified by HSV-1 and HSV-2 has very similar properties. HSV-1 and HSV-2 endonuclease cleave covalently closed circular DNA to yield, firstly, nicked circles and then linear DNA which is subsequently hydrolyzed to small oligonucleotides. Cleavage does not appear to be base sequence specific. Conversion of nicked circles to linear DNA and subsequent degradation of linear DNA occurs more rapidly in the presence of Mg(2+) than Mn(2+) presumably by virtue of the presence of the exonuclease activity. Nonsuperhelical covalently closed circular duplex DNA is cleaved by the endonucleases at a rate 60 times slower than the rate observed on the supercoiled form. These data indicate that the HSV-1 and HSV-2 endonuclease preferentially recognize single-stranded DNA regions."}
{"id": "PMID:228070", "title": "Polypeptides of the Epstein-Barr virus membrane antigen complex.", "content": "Epstein-Barr virus (EBV)-associated membrane antigens have been purified from the plasma membranes of the producer cell line P3HR-1 NONO. The antigens were assayed with a specific rabbit anti-ebv antiserum using an 125I-labeled staphylococcal protein A binding assay. The antigens have been shown to be present on purified plasma membranes. Treatment of the plasma membranes with Triton X-100 allows the separation of two antigenically distinct classes of antigens, one soluble and one insoluble in the detergent. Immunoprecipitates of [125I5- and [35S]methionine-labeled, detergent-soluble antigens contained three major polypeptides of molecular weights of 350,000, 140,000, and 75,003 (on 7.5% sodium dodecyl sulfate-polyacrylamide gel electrophoresis) and several minor components. These polypeptides were all specifically precipitated from four EBV-producer cell lines, P3HR-1, P3HR-1 NONO, B95-8, and 7744. They could not be precipitated from producer cell lines treated with phosphonoacetic acid, which inhibits late viral functions, nor could they be precipitated from nonproducer cell lines. The 350,000 and 75,000 molecular weight polypeptides bound to Ricin and lentil lectin columns; however, most of the 140,000 molecular weight material did not. A component of molecular weight 220,000 (prominent only in P3HR-1 NONO) was probably a degradation product of the 350,000 molecular weight polypeptide.", "contents": "Polypeptides of the Epstein-Barr virus membrane antigen complex. Epstein-Barr virus (EBV)-associated membrane antigens have been purified from the plasma membranes of the producer cell line P3HR-1 NONO. The antigens were assayed with a specific rabbit anti-ebv antiserum using an 125I-labeled staphylococcal protein A binding assay. The antigens have been shown to be present on purified plasma membranes. Treatment of the plasma membranes with Triton X-100 allows the separation of two antigenically distinct classes of antigens, one soluble and one insoluble in the detergent. Immunoprecipitates of [125I5- and [35S]methionine-labeled, detergent-soluble antigens contained three major polypeptides of molecular weights of 350,000, 140,000, and 75,003 (on 7.5% sodium dodecyl sulfate-polyacrylamide gel electrophoresis) and several minor components. These polypeptides were all specifically precipitated from four EBV-producer cell lines, P3HR-1, P3HR-1 NONO, B95-8, and 7744. They could not be precipitated from producer cell lines treated with phosphonoacetic acid, which inhibits late viral functions, nor could they be precipitated from nonproducer cell lines. The 350,000 and 75,000 molecular weight polypeptides bound to Ricin and lentil lectin columns; however, most of the 140,000 molecular weight material did not. A component of molecular weight 220,000 (prominent only in P3HR-1 NONO) was probably a degradation product of the 350,000 molecular weight polypeptide."}
{"id": "PMID:228071", "title": "Infectivity of the DNA from four isolates of JC virus.", "content": "The infectivity of JC virus DNA was demonstrated in its most permissive cell culture, primary human fetal glial cells. The amount of infectivity observed in these heterogeneous cultures varied considerably between batches of cells. Contrary to results obtained with the papovaviruses simian virus 40 and BK virus, the calcium technique (F. L. Graham and A. J. van der Eb, Virology 52:456--467, 1973) was found to be more efficient at promoting JC virus DNA infectivity than the DEAE-dextran method (J. H. McCutchan and J. S. Pagano, J. Natl. Cancer Inst. 41:351--357, 1968): maximum infectivity titers of 4 x 10-(4) and 6 x 10(3) fluorescent cell units per microgram of DNA, respectively. These values represent an approximate recovery of infectivity from virus of between 0.02 and 0.14%. Comparisons of infectivity of DNAs obtained from four isolates of JC virus and which differed in their degrees of heterogeneity did not reveal significant differences. The JC virus DNA was not infectious in primary human fetal lung and kidney cells.", "contents": "Infectivity of the DNA from four isolates of JC virus. The infectivity of JC virus DNA was demonstrated in its most permissive cell culture, primary human fetal glial cells. The amount of infectivity observed in these heterogeneous cultures varied considerably between batches of cells. Contrary to results obtained with the papovaviruses simian virus 40 and BK virus, the calcium technique (F. L. Graham and A. J. van der Eb, Virology 52:456--467, 1973) was found to be more efficient at promoting JC virus DNA infectivity than the DEAE-dextran method (J. H. McCutchan and J. S. Pagano, J. Natl. Cancer Inst. 41:351--357, 1968): maximum infectivity titers of 4 x 10-(4) and 6 x 10(3) fluorescent cell units per microgram of DNA, respectively. These values represent an approximate recovery of infectivity from virus of between 0.02 and 0.14%. Comparisons of infectivity of DNAs obtained from four isolates of JC virus and which differed in their degrees of heterogeneity did not reveal significant differences. The JC virus DNA was not infectious in primary human fetal lung and kidney cells."}
{"id": "PMID:228072", "title": "Organization of mouse mammary tumor virus-specific DNA endogenous to BALB/c mice.", "content": "We used restriction endonucleases to prepare physical maps of the mouse mammary tumor virus (MMTV)-specific DNA endogenous to the BALB/c mouse strain. The mapping was facilitated by the DNA transfer procedure, using complementary DNAs specific for the whole and for the 3' terminus of MMTV RNA to detect fragments containing viral sequences. The strategies used for the arrangement of fragments into physical maps included sequential digestions with two or three enzymes; preparative isolation of EcoRI fragments containing viral sequences; and comparisons of virus-specific fragments derived from the DNA of several mouse strains. Most of the MMTV-related DNA in the BALB/c genome is organized into two units (II and III) which strongly resemble proviruses acquired upon horizontal infection with milk-borne strains of MMTV and other retroviruses. These units contain approximately 6.0 x 10(6) Mr of apparently uninterrupted viral sequences, they bear redundant sequences totaling at least 700 to 800 base pairs at their termini, and the terminal redundancies include sequences derived from the 3' end of MMTV RNA. Units II and III are closely related in that they share 12 of 14 recognition sites for endonucleases, but cellular sequences flanking units II and III are dissimilar by this criterion. The remainder of the MMTV-related DNA endogenous to BALB/c mice is found in a single subgenomic unit (unit I) with a complexity of ca. 2 x 10(6) Mr; the structure of this unit has not been further defined. These results support the hypotheses that endogenous proviruses have been acquired by infection of germinal tissues with MMTV. The physical maps are also useful for identifying the MMTV genomes endogenous to BALB/c mice in studies of the natural history of mammary tumorigenesis.", "contents": "Organization of mouse mammary tumor virus-specific DNA endogenous to BALB/c mice. We used restriction endonucleases to prepare physical maps of the mouse mammary tumor virus (MMTV)-specific DNA endogenous to the BALB/c mouse strain. The mapping was facilitated by the DNA transfer procedure, using complementary DNAs specific for the whole and for the 3' terminus of MMTV RNA to detect fragments containing viral sequences. The strategies used for the arrangement of fragments into physical maps included sequential digestions with two or three enzymes; preparative isolation of EcoRI fragments containing viral sequences; and comparisons of virus-specific fragments derived from the DNA of several mouse strains. Most of the MMTV-related DNA in the BALB/c genome is organized into two units (II and III) which strongly resemble proviruses acquired upon horizontal infection with milk-borne strains of MMTV and other retroviruses. These units contain approximately 6.0 x 10(6) Mr of apparently uninterrupted viral sequences, they bear redundant sequences totaling at least 700 to 800 base pairs at their termini, and the terminal redundancies include sequences derived from the 3' end of MMTV RNA. Units II and III are closely related in that they share 12 of 14 recognition sites for endonucleases, but cellular sequences flanking units II and III are dissimilar by this criterion. The remainder of the MMTV-related DNA endogenous to BALB/c mice is found in a single subgenomic unit (unit I) with a complexity of ca. 2 x 10(6) Mr; the structure of this unit has not been further defined. These results support the hypotheses that endogenous proviruses have been acquired by infection of germinal tissues with MMTV. The physical maps are also useful for identifying the MMTV genomes endogenous to BALB/c mice in studies of the natural history of mammary tumorigenesis."}
{"id": "PMID:228073", "title": "Polyprotein precursors to mouse mammary tumor virus proteins.", "content": "Mouse mammary tumor virus (MMTV) derived from the culture medium of GR cells contained seven proteins, identified as gp55, gp33, p25, pp20, p16, p12, and p10. The major viral phosphoprotein was the 20,000-molecular-weight protein, pp20. Immunoprecipitation of cytoplasmic extracts from pulse-labeled GR cells identified three MMTV gag-specific proteins, termed Pr78(gag), Pr110(gag), and Pr180(gag+). These intracellular polyproteins were precipitable from cytoplasmic extracts by antisera to virions p25 and p12 but not by antisera to gp55. The major intracellular gag-specific precursor polyprotein, Pr78(gag), contained antigenic determinants and tryptic peptides characteristic of p25, p12, p10, and presumably pp20. This precursor is presumably derived from nascent chain cleavage or rapid posttranslational cleavage of the larger intracellular precursor-like protein, designated Pr110(gag). Pr110(gag) contained all but one of the leucine-containing tryptic peptides of Pr78(gag), plus several additional peptides. In addition to Pr78(gag) and Pr110(gag), monospecific antisera to virion p12 and p25 were also capable of precipitating from pulse-labeled cells a small amount of a 180,000-molecular-weight precursor-like protein, designated Pr180(gag+). This large polyprotein contained nearly all of the leucine-containing tryptic peptides of Pr78(gag) and Pr110(gag) plus several additional peptides. By analogy to type C viral systems, Pr180(gag+) is presumed to represent a gag-pol common precursor which is the major pathway for synthesis of MMTV polymerase. Immunoprecipitation of cytoplasmic extracts from pulse-labeled cells with antisera to gp55 identified two env-specific proteins, designated gPr76(env) and gP79(env). The major env precursor, gPr76(env), could be labeled with radioactive glucosamine and was shown to contain antigenic determinants and tryptic peptides characteristic of gp55 and gp33. A minor glycoprotein, gP79(env), contained both fucose and glucosamine and was precipitable from cytoplasmic extracts with monospecific serum to gp55. It is suggested that gP79(env) represents fucosylated gPr76(env) which is transiently synthesized and cleaved rapidly into gp55 and gp33.", "contents": "Polyprotein precursors to mouse mammary tumor virus proteins. Mouse mammary tumor virus (MMTV) derived from the culture medium of GR cells contained seven proteins, identified as gp55, gp33, p25, pp20, p16, p12, and p10. The major viral phosphoprotein was the 20,000-molecular-weight protein, pp20. Immunoprecipitation of cytoplasmic extracts from pulse-labeled GR cells identified three MMTV gag-specific proteins, termed Pr78(gag), Pr110(gag), and Pr180(gag+). These intracellular polyproteins were precipitable from cytoplasmic extracts by antisera to virions p25 and p12 but not by antisera to gp55. The major intracellular gag-specific precursor polyprotein, Pr78(gag), contained antigenic determinants and tryptic peptides characteristic of p25, p12, p10, and presumably pp20. This precursor is presumably derived from nascent chain cleavage or rapid posttranslational cleavage of the larger intracellular precursor-like protein, designated Pr110(gag). Pr110(gag) contained all but one of the leucine-containing tryptic peptides of Pr78(gag), plus several additional peptides. In addition to Pr78(gag) and Pr110(gag), monospecific antisera to virion p12 and p25 were also capable of precipitating from pulse-labeled cells a small amount of a 180,000-molecular-weight precursor-like protein, designated Pr180(gag+). This large polyprotein contained nearly all of the leucine-containing tryptic peptides of Pr78(gag) and Pr110(gag) plus several additional peptides. By analogy to type C viral systems, Pr180(gag+) is presumed to represent a gag-pol common precursor which is the major pathway for synthesis of MMTV polymerase. Immunoprecipitation of cytoplasmic extracts from pulse-labeled cells with antisera to gp55 identified two env-specific proteins, designated gPr76(env) and gP79(env). The major env precursor, gPr76(env), could be labeled with radioactive glucosamine and was shown to contain antigenic determinants and tryptic peptides characteristic of gp55 and gp33. A minor glycoprotein, gP79(env), contained both fucose and glucosamine and was precipitable from cytoplasmic extracts with monospecific serum to gp55. It is suggested that gP79(env) represents fucosylated gPr76(env) which is transiently synthesized and cleaved rapidly into gp55 and gp33."}
{"id": "PMID:228074", "title": "Isolation and characterization of polyoma virus genomes with deletions between the origin of viral DNA replication and the site of initiation of translation in the early region.", "content": "We introduced deletions in the early region of the polyoma virus genome near the HaeII restriction enzyme cleavage site, between the origin of viral DNA replication and the site of initiation of translation of the polyoma T antigens. We analyzed the DNA of the deletion mutants by restriction enzyme digestion. Four of the mutants had deletions beginning very close to the HaeII site and extending clockwise toward the site of initiation of translation. The deletions near the HaeII site varied in size from about 10 base pairs to about 55 base pairs. The mutants containing deletions near the HaeII site were capable of lytic growth in mouse 3T6 cells and were capable of transforming rat F2408 cells, as judged by focus formation.", "contents": "Isolation and characterization of polyoma virus genomes with deletions between the origin of viral DNA replication and the site of initiation of translation in the early region. We introduced deletions in the early region of the polyoma virus genome near the HaeII restriction enzyme cleavage site, between the origin of viral DNA replication and the site of initiation of translation of the polyoma T antigens. We analyzed the DNA of the deletion mutants by restriction enzyme digestion. Four of the mutants had deletions beginning very close to the HaeII site and extending clockwise toward the site of initiation of translation. The deletions near the HaeII site varied in size from about 10 base pairs to about 55 base pairs. The mutants containing deletions near the HaeII site were capable of lytic growth in mouse 3T6 cells and were capable of transforming rat F2408 cells, as judged by focus formation."}
{"id": "PMID:228075", "title": "Construction and analysis of viable deletion mutants of polyoma virus.", "content": "Viable mutants of polyoma with small deletions ranging in size from 2 to 75 base pairs were obtained by infecting 3T3 cells with polyoma DNA that had been cleaved once with HaeII endonuclease or with DNase-Mn2+ digestion. The HaeII endonuclease-cleaved DNA yielded mutants with deletions at map position 72--73, whereas the mutants generated by DNase I-Mn2+ digestion had deletions either at map position 72--73 or within the map coordinates 92 and 99. Both groups of mutants appeared to grow as well as wild-type virus in 3T3 cells. The deletions at map position 72--73 did not alter the virus's ability to transform rat cells. Hence, the region just to the early side of the origin of DNA replication is not essential for vegetative growth or transformation. But the mutants with deletions in the region between map coordinates 92 and 99, a segment thought to code for polyoma large and middle T antigens (Hutchinson et al., Cell 15:65--77, 1978; Smart and Ito, Cell 15:1427--1437, 1978; Soeda et al., Cell 17:357--370, 1979), transformed rat cells at 0.2 to 0.05 the efficiency of wild-type virus.", "contents": "Construction and analysis of viable deletion mutants of polyoma virus. Viable mutants of polyoma with small deletions ranging in size from 2 to 75 base pairs were obtained by infecting 3T3 cells with polyoma DNA that had been cleaved once with HaeII endonuclease or with DNase-Mn2+ digestion. The HaeII endonuclease-cleaved DNA yielded mutants with deletions at map position 72--73, whereas the mutants generated by DNase I-Mn2+ digestion had deletions either at map position 72--73 or within the map coordinates 92 and 99. Both groups of mutants appeared to grow as well as wild-type virus in 3T3 cells. The deletions at map position 72--73 did not alter the virus's ability to transform rat cells. Hence, the region just to the early side of the origin of DNA replication is not essential for vegetative growth or transformation. But the mutants with deletions in the region between map coordinates 92 and 99, a segment thought to code for polyoma large and middle T antigens (Hutchinson et al., Cell 15:65--77, 1978; Smart and Ito, Cell 15:1427--1437, 1978; Soeda et al., Cell 17:357--370, 1979), transformed rat cells at 0.2 to 0.05 the efficiency of wild-type virus."}
{"id": "PMID:228076", "title": "Deletion mutants of polyoma virus defining a nonessential region between the origin of replication and the initiation codon for early proteins.", "content": "Mutants of polyoma virus with deletions as large as 90 base pairs were isolated by selecting spontaneously arising genomes resistant to endonuclease HaeII or by treating HaeII- or BglI- cleaved linear DNAs with S1 nuclease and exonuclease III. All of the mutants were viable and, therefore, defined a nonessential region in the polyoma genome between the origin of DNA replication and the initiation codon for translation of early proteins. Several mutants with large deletions had altered growth properties, giving smaller plaques and lower virus yields than the parental wild-type virus. These viruses may lack sites that are important for DNA replication or for transcription and translation of early mRNA's. All of the mutants tested could transform BHK-21 cells to anchorage independence.", "contents": "Deletion mutants of polyoma virus defining a nonessential region between the origin of replication and the initiation codon for early proteins. Mutants of polyoma virus with deletions as large as 90 base pairs were isolated by selecting spontaneously arising genomes resistant to endonuclease HaeII or by treating HaeII- or BglI- cleaved linear DNAs with S1 nuclease and exonuclease III. All of the mutants were viable and, therefore, defined a nonessential region in the polyoma genome between the origin of DNA replication and the initiation codon for translation of early proteins. Several mutants with large deletions had altered growth properties, giving smaller plaques and lower virus yields than the parental wild-type virus. These viruses may lack sites that are important for DNA replication or for transcription and translation of early mRNA's. All of the mutants tested could transform BHK-21 cells to anchorage independence."}
{"id": "PMID:228077", "title": "Evidence for the identity of shared 5'-terminal sequences between genome RNA and subgenomic mRNA's of B77 avian sarcoma virus.", "content": "The polyribosomal fraction from chicken embryo fibroblasts infected with B77 avian sarcoma virus contained 38S, 28S, and 21S virus-specific RNAs in which sequences identical to the 5'-terminal 101 bases of the 38S genome RNA were present. The only polyadenylic acid-containing RNA species with 5' sequences which was detectable in purified virions had a sedimentation coefficient of 38S. This evidence is consistent with the hypothesis that a leader sequence derived from the 5' terminus of the RNA is spliced to the bodies of the 28S and 21S mRNA's, both of which have been shown previously to be derived from the 3' terminal half of the 38S RNA. The entire 101-base 5' terminal sequence of the genome RNA appeared to be present in the majority of the subgenomic intracellular virus-specific mRNA's, as established by several different methods. First, the extent of hybridization of DNA complementary to the 5'-terminal 101 bases of the genome to polyadenylic acid-containing subgenomic RNA was similar to the extent of its hybridization to 38S RNA from infected cells and from purified virions. Second, the fraction of the total cellular polyadenylic acid-containing RNA with 5' sequences was similar to the fraction of RNA containing sequences identical to the extreme 3' terminus of the genome RNA when calculated by the rate of hybridization of the appropriate complementary DNA probes. This suggests that most intracellular virus-specific RNA molecules contain sequences identical to those present in the 5'-terminal 101 bases of the genome. Third, the size of most of the radioactively labeled DNA complementary to the 5'-terminal 101 bases of the genome remained unchanged after the probe was annealed to either intracellular 38S RNA or to various size classes of subgenomic RNA and the hybrids were digested with S1 nuclease and denatured with alkali. However, after this procedure some DNA fragments of lower molecular weight were present. This was not the case when the DNA complementary to the 5'-terminal 101 bases of the genome was annealed to 38S genome RNA. These results suggest that, although the majority of the intracellular RNA contains the entire 101-base 5'-terminal leader sequence, a small population of virus-specific RNAs exist that contain either a shortened 5' leader sequence or additional splicing in the terminal 101 bases.", "contents": "Evidence for the identity of shared 5'-terminal sequences between genome RNA and subgenomic mRNA's of B77 avian sarcoma virus. The polyribosomal fraction from chicken embryo fibroblasts infected with B77 avian sarcoma virus contained 38S, 28S, and 21S virus-specific RNAs in which sequences identical to the 5'-terminal 101 bases of the 38S genome RNA were present. The only polyadenylic acid-containing RNA species with 5' sequences which was detectable in purified virions had a sedimentation coefficient of 38S. This evidence is consistent with the hypothesis that a leader sequence derived from the 5' terminus of the RNA is spliced to the bodies of the 28S and 21S mRNA's, both of which have been shown previously to be derived from the 3' terminal half of the 38S RNA. The entire 101-base 5' terminal sequence of the genome RNA appeared to be present in the majority of the subgenomic intracellular virus-specific mRNA's, as established by several different methods. First, the extent of hybridization of DNA complementary to the 5'-terminal 101 bases of the genome to polyadenylic acid-containing subgenomic RNA was similar to the extent of its hybridization to 38S RNA from infected cells and from purified virions. Second, the fraction of the total cellular polyadenylic acid-containing RNA with 5' sequences was similar to the fraction of RNA containing sequences identical to the extreme 3' terminus of the genome RNA when calculated by the rate of hybridization of the appropriate complementary DNA probes. This suggests that most intracellular virus-specific RNA molecules contain sequences identical to those present in the 5'-terminal 101 bases of the genome. Third, the size of most of the radioactively labeled DNA complementary to the 5'-terminal 101 bases of the genome remained unchanged after the probe was annealed to either intracellular 38S RNA or to various size classes of subgenomic RNA and the hybrids were digested with S1 nuclease and denatured with alkali. However, after this procedure some DNA fragments of lower molecular weight were present. This was not the case when the DNA complementary to the 5'-terminal 101 bases of the genome was annealed to 38S genome RNA. These results suggest that, although the majority of the intracellular RNA contains the entire 101-base 5'-terminal leader sequence, a small population of virus-specific RNAs exist that contain either a shortened 5' leader sequence or additional splicing in the terminal 101 bases."}
{"id": "PMID:228078", "title": "Analysis of the src gene of sarcoma viruses generated by recombination between transformation-defective mutants and quail cellular sequences.", "content": "Tumors were produced in quails about 2 months after injection with a transformation-defective mutant of the Schmidt-Ruppin strain of Rous sarcoma virus, subgroup A (SR-A), that retains a small portion of the src gene. Sarcoma viruses were isolated from each of five such tumors. A transformation-defective mutant which has a nearly complete deletion of the src gene was unable to induce tumors. The avian sarcoma viruses recovered from quail tumors (rASV-Q) had biological properties similar to those of the avian sarcoma viruses previously acquired from chicken tumors (rASV-C); these chicken tumors had been induced by the same transformation-defective mutants. Both rASV-Q and rASV-C transformed cells in culture with similar focus morphology and produced tumors within 7 to 14 days after injection into chickens or quails. The size of rASV-Q genomic RNA was indistinguishable from that of SR-A by polyacrylamide gel electrophoresis. The sequences of rASV-Q RNA genomes were analyzed and compared with those of the parental transformation-defective virus, SR-A and of rASV-C by RNase T1 fingerprinting and oligonucleotide mapping. We found that the src sequences of all five isolates of rASV-Q were identical to each other but different from those of SR-A and rASV-C. Of 13 oligonucleotides of rASV-Q identified as src specific, two were not found in either SR-A or rASV-C RNA. Furthermore, some oligonucleotides present in SR-A or rASV-C or both were absent in rASV-Q. No differences were found for the sequences outside the src region in any of the viruses examined. In addition, rASV-Q-infected cells possessed a 60,000-dalton protein specifically precipitable by rabbit serum raised against SR-D-induced tumors. The facts that the src sequences are essentially the same for rASV's recovered from one animal species and different for rASV's obtained from different species provide conclusive evidence that cellular sequences of normal birds were inserted into the viral genome and supplied to the resulting recombinant viruses genetic information for cell transformation.", "contents": "Analysis of the src gene of sarcoma viruses generated by recombination between transformation-defective mutants and quail cellular sequences. Tumors were produced in quails about 2 months after injection with a transformation-defective mutant of the Schmidt-Ruppin strain of Rous sarcoma virus, subgroup A (SR-A), that retains a small portion of the src gene. Sarcoma viruses were isolated from each of five such tumors. A transformation-defective mutant which has a nearly complete deletion of the src gene was unable to induce tumors. The avian sarcoma viruses recovered from quail tumors (rASV-Q) had biological properties similar to those of the avian sarcoma viruses previously acquired from chicken tumors (rASV-C); these chicken tumors had been induced by the same transformation-defective mutants. Both rASV-Q and rASV-C transformed cells in culture with similar focus morphology and produced tumors within 7 to 14 days after injection into chickens or quails. The size of rASV-Q genomic RNA was indistinguishable from that of SR-A by polyacrylamide gel electrophoresis. The sequences of rASV-Q RNA genomes were analyzed and compared with those of the parental transformation-defective virus, SR-A and of rASV-C by RNase T1 fingerprinting and oligonucleotide mapping. We found that the src sequences of all five isolates of rASV-Q were identical to each other but different from those of SR-A and rASV-C. Of 13 oligonucleotides of rASV-Q identified as src specific, two were not found in either SR-A or rASV-C RNA. Furthermore, some oligonucleotides present in SR-A or rASV-C or both were absent in rASV-Q. No differences were found for the sequences outside the src region in any of the viruses examined. In addition, rASV-Q-infected cells possessed a 60,000-dalton protein specifically precipitable by rabbit serum raised against SR-D-induced tumors. The facts that the src sequences are essentially the same for rASV's recovered from one animal species and different for rASV's obtained from different species provide conclusive evidence that cellular sequences of normal birds were inserted into the viral genome and supplied to the resulting recombinant viruses genetic information for cell transformation."}
{"id": "PMID:228079", "title": "Hormonal regulation of murine mammary tumor virus RNA expression during mammary tumorigenesis in BALB/c mice.", "content": "The effects of glucocorticoids and prolactin on murine mammary tumor virus (MuMTV) RNA expression in preneoplastic outgrowth lines and mammary tumors in BALB/c mice were investigated. Hyperplastic alveolar nodules (HAN) and a ductal hyperplasia (DH) are induced in virgin BALB/c mice by prolonged hormonal stimulation or treatment with 7,12-dimethylbenz(a)anthracene or both. Mice bearing HAN or DH outgrowth lines and mammary tumors that arose from the outgrowth lines were treated with glucocorticoids or prolactin. MuMTV RNA was quantitated by hybridization with a representative complementary DNA probe specific for MuMTV RNA. Prolactin treatment did not increase MuMTV RNA in the BALB/c HAN or DH outgrowth lines or tumors. MuMTV RNA increased after glucocorticoid treatment in the C3, C4, and C5 HAN outgrowth lines and in tumors that arose from the D1, D2, C4, and C5 HAN and CD8 DH outgrowth lines. No increase in MuMTV RNA with glucocorticoid treatment was observed in the D1 or D2 HAN outgrowth line, in the CD8 DH outgrowth lines, and in tumors that arose from the C3 HAN outgrowth line. The ability of glucocorticoids to stimulate MuMTV expression was specific since the response was dose dependent and specific for glucocorticoid hormones. Glucocorticoid treatment did not increase the level of type C viral RNA in the majority of hormone- or 7,12-dimethylbenz(a)anthracene-induced HAN outgrowth lines or tumors. These observations suggested that glucocorticoids may influence MuMTV expression during mammary tumorigenesis in BALB/c mice.", "contents": "Hormonal regulation of murine mammary tumor virus RNA expression during mammary tumorigenesis in BALB/c mice. The effects of glucocorticoids and prolactin on murine mammary tumor virus (MuMTV) RNA expression in preneoplastic outgrowth lines and mammary tumors in BALB/c mice were investigated. Hyperplastic alveolar nodules (HAN) and a ductal hyperplasia (DH) are induced in virgin BALB/c mice by prolonged hormonal stimulation or treatment with 7,12-dimethylbenz(a)anthracene or both. Mice bearing HAN or DH outgrowth lines and mammary tumors that arose from the outgrowth lines were treated with glucocorticoids or prolactin. MuMTV RNA was quantitated by hybridization with a representative complementary DNA probe specific for MuMTV RNA. Prolactin treatment did not increase MuMTV RNA in the BALB/c HAN or DH outgrowth lines or tumors. MuMTV RNA increased after glucocorticoid treatment in the C3, C4, and C5 HAN outgrowth lines and in tumors that arose from the D1, D2, C4, and C5 HAN and CD8 DH outgrowth lines. No increase in MuMTV RNA with glucocorticoid treatment was observed in the D1 or D2 HAN outgrowth line, in the CD8 DH outgrowth lines, and in tumors that arose from the C3 HAN outgrowth line. The ability of glucocorticoids to stimulate MuMTV expression was specific since the response was dose dependent and specific for glucocorticoid hormones. Glucocorticoid treatment did not increase the level of type C viral RNA in the majority of hormone- or 7,12-dimethylbenz(a)anthracene-induced HAN outgrowth lines or tumors. These observations suggested that glucocorticoids may influence MuMTV expression during mammary tumorigenesis in BALB/c mice."}
{"id": "PMID:228080", "title": "Biophysical and biochemical characterization of five animal viruses with bisegmented double-stranded RNA genomes.", "content": "Infectious pancreatic necrosis virus of fish, infectious bursal disease virus of chickens, Tellina virus and oyster virus of bivalve molluscs, and drosophila X virus of Drosophila melanogaster are naked icosahedral viruses with an electron microscopic diameter of 58 to 60 nm. The genome of each of these viruses consists of two segments of double-stranded RNA (molecular weight range between 2.6 x 10(6) and 2.2 x 10(6), and the virion, capsid proteins fall into three size class categories (large, medium, and small; ranging from 100,000 to 27,000) as determined by polyacrylamide slab gel electrophoresis. The hydrodynamic properties of the five viruses are similar as determined by analytical ultracentrifugation and laser quasi-elastic, light-scattering spectroscopy. The calculated particle weights range between 55 x 10(6) and 81 x 10(6). Tryptic peptide comparisons of 125I-labeled virion proteins showed that five viruses are different from each other, although there was considerable overlap in the peptide maps of the three aquatic viruses, indicting a degree of relatedness. Cross-neutralization tests indicated that drosophila X, infectious pancreatic necrosis, and infectious bursal disease viruses were different from each other and from oyster and Tellina viruses. The same test showed oyster and Tellina viruses to be related. The biochemical and biophysical properties of the five viruses cannt be included in the family Reoviridae or in any of the present virus genera.", "contents": "Biophysical and biochemical characterization of five animal viruses with bisegmented double-stranded RNA genomes. Infectious pancreatic necrosis virus of fish, infectious bursal disease virus of chickens, Tellina virus and oyster virus of bivalve molluscs, and drosophila X virus of Drosophila melanogaster are naked icosahedral viruses with an electron microscopic diameter of 58 to 60 nm. The genome of each of these viruses consists of two segments of double-stranded RNA (molecular weight range between 2.6 x 10(6) and 2.2 x 10(6), and the virion, capsid proteins fall into three size class categories (large, medium, and small; ranging from 100,000 to 27,000) as determined by polyacrylamide slab gel electrophoresis. The hydrodynamic properties of the five viruses are similar as determined by analytical ultracentrifugation and laser quasi-elastic, light-scattering spectroscopy. The calculated particle weights range between 55 x 10(6) and 81 x 10(6). Tryptic peptide comparisons of 125I-labeled virion proteins showed that five viruses are different from each other, although there was considerable overlap in the peptide maps of the three aquatic viruses, indicting a degree of relatedness. Cross-neutralization tests indicated that drosophila X, infectious pancreatic necrosis, and infectious bursal disease viruses were different from each other and from oyster and Tellina viruses. The same test showed oyster and Tellina viruses to be related. The biochemical and biophysical properties of the five viruses cannt be included in the family Reoviridae or in any of the present virus genera."}
{"id": "PMID:228081", "title": "In vitro reassembly of infectious polyoma virions.", "content": "Initial experiments in our laboratory have successfully reassembled infectious polyoma virions from dissociated virion products. Virions treated with ethyleneglycol-bis-N,N'-tetraacetic acid and the reducing agent beta-mercaptoethanol at pH 7.5 were dissociated to a 48S DNA-protein complex and capsomere subunits. The virion dissociation products were not infectious by plaque assay and lacked hemagglutination activity. These virion dissociation products were reassembled to intact virions by overnight dialysis against a reassembly buffer containing CaCl2, dimethyl sulfoxide, and Triton X-100 in phosphate-buffered saline at pH 7.4. The biophysical characteristics of the reassembled virions were identical to those of untreated virions in that the reassembled virions had a sedimentation value of 240S in sucrose gradients and a buoyant density of 1.315 g/cm3 in CsCl isopycnic gradients. The reassembled virions were intact as determined by electron microscopy and were found to be 60% resistant to DNase I treatment. Biologically, the reassembled purified virions were found to partially regain both hemagglutinating activity and plaque-forming ability.", "contents": "In vitro reassembly of infectious polyoma virions. Initial experiments in our laboratory have successfully reassembled infectious polyoma virions from dissociated virion products. Virions treated with ethyleneglycol-bis-N,N'-tetraacetic acid and the reducing agent beta-mercaptoethanol at pH 7.5 were dissociated to a 48S DNA-protein complex and capsomere subunits. The virion dissociation products were not infectious by plaque assay and lacked hemagglutination activity. These virion dissociation products were reassembled to intact virions by overnight dialysis against a reassembly buffer containing CaCl2, dimethyl sulfoxide, and Triton X-100 in phosphate-buffered saline at pH 7.4. The biophysical characteristics of the reassembled virions were identical to those of untreated virions in that the reassembled virions had a sedimentation value of 240S in sucrose gradients and a buoyant density of 1.315 g/cm3 in CsCl isopycnic gradients. The reassembled virions were intact as determined by electron microscopy and were found to be 60% resistant to DNase I treatment. Biologically, the reassembled purified virions were found to partially regain both hemagglutinating activity and plaque-forming ability."}
{"id": "PMID:228082", "title": "Intracellular localization of viral polypeptides during simian virus 40 infection.", "content": "African green monkey kidney cells infected by simian virus 40 were analyzed by immunofluorescence techniques for the nature and the time course of the appearance of viral polypeptides during infection. Reagents used in the study were anti-Vpl sera and affinity-purified anti-Vpl immunoglobulin G, anti-Vp3 sera, antivirus (anti-V) sera, and anti-tumor antigen sera. The results are summarized as follows. (i) Three types of staining, nuclear, perinuclear, and perinuclear accompanied by cytoplasmic staining, were observed in infected cells in reaction with anti-vpl antibody. In addition, a highly structured staining was observed at the periphery of nuclei of infected cells late in infection. (ii) In reaction with anti-Vp3 serum, the staining was confined within nuclei of cells throughout infection. (iii) Vp1 and Vp3 antigens seem to occupy different spacial regions of the nuclear area in cells. (iv) Vp1 and Vp3 antigens were expressed simultaneously during infection. (v) Centriolar staining observed early in infection paralleled the appearance of tumor (T-) antigen until 24 h after infection, after which time the frequency of positive centriolar staining decreased as infection progressed. (vi) T-antigen was first expressed at about 8 h after infection, and Vp1 and Vp3 antigens were first expressed at about 20 h after infection.", "contents": "Intracellular localization of viral polypeptides during simian virus 40 infection. African green monkey kidney cells infected by simian virus 40 were analyzed by immunofluorescence techniques for the nature and the time course of the appearance of viral polypeptides during infection. Reagents used in the study were anti-Vpl sera and affinity-purified anti-Vpl immunoglobulin G, anti-Vp3 sera, antivirus (anti-V) sera, and anti-tumor antigen sera. The results are summarized as follows. (i) Three types of staining, nuclear, perinuclear, and perinuclear accompanied by cytoplasmic staining, were observed in infected cells in reaction with anti-vpl antibody. In addition, a highly structured staining was observed at the periphery of nuclei of infected cells late in infection. (ii) In reaction with anti-Vp3 serum, the staining was confined within nuclei of cells throughout infection. (iii) Vp1 and Vp3 antigens seem to occupy different spacial regions of the nuclear area in cells. (iv) Vp1 and Vp3 antigens were expressed simultaneously during infection. (v) Centriolar staining observed early in infection paralleled the appearance of tumor (T-) antigen until 24 h after infection, after which time the frequency of positive centriolar staining decreased as infection progressed. (vi) T-antigen was first expressed at about 8 h after infection, and Vp1 and Vp3 antigens were first expressed at about 20 h after infection."}
{"id": "PMID:228083", "title": "Density dependent inhibition of both growth and T-antigen expression in revertants isolated from simian virus 40-transformed mouse SVT2 cells.", "content": "Phenotypic revertants were isolated from simian virus 40-transformed cells in order to examine the relationship between simian virus 40 T-antigen expression and G1 arrest of growth. Revertant clones with increased adherence were selected from cultures of SVT2, a simian virus 40-transformed BALB/c mouse cell line, and screened to find arrestable revertant clones which inhibited DNA synthesis when crowded. The clones selected from untreated SVT2 were unstable and showed little or no inhibition of DNA synthesis when crowded. Stable revertants were found after treatment of SVT2 with Colcemid to increase ploidy. The stable revertants all lost most transformed growth properties tested, including tumorigenicity, but only a few showed the same degree of inhibition of DNA synthesis at high cell density as BALB/3T3. All revertant clones expressed T antigen at low cell density. Three revertants showed coordinate inhibition of DNA synthesis and apparent loss of T antigen at high cell density. We suggest that changes in gene dosage rather than mutations caused the altered properties of the new revertants and that continued DNA synthesis in confluent cultures may be the transformed phenotype that requires the least simian virus 40 T antigen.", "contents": "Density dependent inhibition of both growth and T-antigen expression in revertants isolated from simian virus 40-transformed mouse SVT2 cells. Phenotypic revertants were isolated from simian virus 40-transformed cells in order to examine the relationship between simian virus 40 T-antigen expression and G1 arrest of growth. Revertant clones with increased adherence were selected from cultures of SVT2, a simian virus 40-transformed BALB/c mouse cell line, and screened to find arrestable revertant clones which inhibited DNA synthesis when crowded. The clones selected from untreated SVT2 were unstable and showed little or no inhibition of DNA synthesis when crowded. Stable revertants were found after treatment of SVT2 with Colcemid to increase ploidy. The stable revertants all lost most transformed growth properties tested, including tumorigenicity, but only a few showed the same degree of inhibition of DNA synthesis at high cell density as BALB/3T3. All revertant clones expressed T antigen at low cell density. Three revertants showed coordinate inhibition of DNA synthesis and apparent loss of T antigen at high cell density. We suggest that changes in gene dosage rather than mutations caused the altered properties of the new revertants and that continued DNA synthesis in confluent cultures may be the transformed phenotype that requires the least simian virus 40 T antigen."}
{"id": "PMID:228084", "title": "Phosphoproteins of murine hepatitis viruses.", "content": "Four strains of the coronavirus murine hepatitis virus were examined for the presence of phosphorylated proteins. The nucleocapsid protein was determined to contain phosphate covalently linked to serine but not to threonine residues. The nucleocapsid protein was the only phosphorylated protein detected in these strains of murine hepatitis virus.", "contents": "Phosphoproteins of murine hepatitis viruses. Four strains of the coronavirus murine hepatitis virus were examined for the presence of phosphorylated proteins. The nucleocapsid protein was determined to contain phosphate covalently linked to serine but not to threonine residues. The nucleocapsid protein was the only phosphorylated protein detected in these strains of murine hepatitis virus."}
{"id": "PMID:228085", "title": "Differential adsorption of polyoma virions and capsids to mouse kidney cells and guinea pig erythrocytes.", "content": "Adsorption of 125I-labeled polyoma virions and capsids to the surface of mouse kidney cells (MKC) and guinea pig erythrocytes was examined. Purified polyoma capsids lack the ability to compete with polyoma virions for specific binding sites on the surface of MKC. These same capsids were, however, able to block virion adsorption to guinea pig erythrocytes. UV-inactivated virions blocked cellular receptors on MKC and thus inhibited infectious virions from infecting the cells. Capsids were unable to inhibit virion infection of MKC. Adsorption of polyoma virions to MKC and infection of these cells were found to be independent of the ability of the virions to agglutinate guinea pig erythrocytes.", "contents": "Differential adsorption of polyoma virions and capsids to mouse kidney cells and guinea pig erythrocytes. Adsorption of 125I-labeled polyoma virions and capsids to the surface of mouse kidney cells (MKC) and guinea pig erythrocytes was examined. Purified polyoma capsids lack the ability to compete with polyoma virions for specific binding sites on the surface of MKC. These same capsids were, however, able to block virion adsorption to guinea pig erythrocytes. UV-inactivated virions blocked cellular receptors on MKC and thus inhibited infectious virions from infecting the cells. Capsids were unable to inhibit virion infection of MKC. Adsorption of polyoma virions to MKC and infection of these cells were found to be independent of the ability of the virions to agglutinate guinea pig erythrocytes."}
{"id": "PMID:228086", "title": "Physical maps of bovine papillomavirus type 1 and type 2 genomes.", "content": "Physical maps of bovine papillomavirus type 1 and type 2 (BPV-1 and BPV-2) DNA were constructed from analysis of the electrophoretic mobilities of restriction endonuclease cleavage fragments from dual digests. BPV-1 DNA was sensitive to Hind III, HindIII, EcoRI, HpaI, AND BamHI, with all but HindII yielding single scissions. BPV-2 DNA was resistant to EcoRI, and HindIII had one cleavage site whereas HpaI, BamHI, and HindII yielded multiple fragments. Of four BPV-1 isolates examined, DNA from one isolate was resistant to HindIII, and another DNA isolate was resistant to BamHI. The three BPV-2 isolates examined were uniformly sensitive to the restriction endonucleases employed.", "contents": "Physical maps of bovine papillomavirus type 1 and type 2 genomes. Physical maps of bovine papillomavirus type 1 and type 2 (BPV-1 and BPV-2) DNA were constructed from analysis of the electrophoretic mobilities of restriction endonuclease cleavage fragments from dual digests. BPV-1 DNA was sensitive to Hind III, HindIII, EcoRI, HpaI, AND BamHI, with all but HindII yielding single scissions. BPV-2 DNA was resistant to EcoRI, and HindIII had one cleavage site whereas HpaI, BamHI, and HindII yielded multiple fragments. Of four BPV-1 isolates examined, DNA from one isolate was resistant to HindIII, and another DNA isolate was resistant to BamHI. The three BPV-2 isolates examined were uniformly sensitive to the restriction endonucleases employed."}
{"id": "PMID:228088", "title": "Serological studies on sympatric Barbary sheep and mule deer from Palo Duro Canyon, Texas.", "content": "Sera were collected from 12 Barbary sheet (Ammotragus lervia) and 11 mule deer (Odocoileus hemionus) occupying sympatric ranges in Palo Duro Canyon, Texas. These were tested for leptospirosis, brucellosis, bovine virus diarrhea, anaplasmosis, vesicular stomatitis, bluetongue (BT), epizootic hemorrhagic disease (EHD), infectious bovine rhinotracheitis (IBR), and coccidioidomycosis. Serologic reactors were found to IBR in 3 Barbery sheep, BT in 6 Barbary sheep and 6 mule deer and EHD in 3 Barbary sheep and 4 mule deer. Possible ramifications of evidence for these diseases in wild herbivore populations in this area are discussed.", "contents": "Serological studies on sympatric Barbary sheep and mule deer from Palo Duro Canyon, Texas. Sera were collected from 12 Barbary sheet (Ammotragus lervia) and 11 mule deer (Odocoileus hemionus) occupying sympatric ranges in Palo Duro Canyon, Texas. These were tested for leptospirosis, brucellosis, bovine virus diarrhea, anaplasmosis, vesicular stomatitis, bluetongue (BT), epizootic hemorrhagic disease (EHD), infectious bovine rhinotracheitis (IBR), and coccidioidomycosis. Serologic reactors were found to IBR in 3 Barbery sheep, BT in 6 Barbary sheep and 6 mule deer and EHD in 3 Barbary sheep and 4 mule deer. Possible ramifications of evidence for these diseases in wild herbivore populations in this area are discussed."}
{"id": "PMID:228089", "title": "Avian pox in California quail from Oregon.", "content": "California quail (Lophortyx californicus) from several locations in Oregon were examined seasonally between fall 1975 and summer 1978 for avian pox. Pox lesions were present on 66 of 256 (26%) birds from the E.E. Wilson Wildlife Area. None of the remaining 41 birds from other areas was infected. Rates of infection of males and females were equal; juveniles had a slightly, but not significantly, higher prevalence of pox than did adults.", "contents": "Avian pox in California quail from Oregon. California quail (Lophortyx californicus) from several locations in Oregon were examined seasonally between fall 1975 and summer 1978 for avian pox. Pox lesions were present on 66 of 256 (26%) birds from the E.E. Wilson Wildlife Area. None of the remaining 41 birds from other areas was infected. Rates of infection of males and females were equal; juveniles had a slightly, but not significantly, higher prevalence of pox than did adults."}
{"id": "PMID:228090", "title": "Avian pox infection in an American green-winged teal (Anas crecca carolinensis) in Alaska.", "content": "Poxvirus infection was diagnosed on the basis of gross and microscopic appearance plus the presence of typical inclusion bodies in a juvenile American green-winged teal (Anas crecca carolinensis) in Alaska. This constitutes the first known report of avian pox in migratory ducks and the first report of poxvirus infection in wild birds in Alaska.", "contents": "Avian pox infection in an American green-winged teal (Anas crecca carolinensis) in Alaska. Poxvirus infection was diagnosed on the basis of gross and microscopic appearance plus the presence of typical inclusion bodies in a juvenile American green-winged teal (Anas crecca carolinensis) in Alaska. This constitutes the first known report of avian pox in migratory ducks and the first report of poxvirus infection in wild birds in Alaska."}
{"id": "PMID:228091", "title": "Observations on the epidemiology of the herpesvirus of infectous bovine rhinotracheitis/infectious pustular vulvovaginitis in wildebeest.", "content": "Spontaneous vulvovaginitis erupted in wildebeest (Connochaetes taurinus) after betamethasone inoculation. Infectious bovine rhinotracheitis/infectious pustular vulvovaginitis (IBR/IPV) is probably a venereal disease because virgin wildebeest did not develop vulvovaginitis after betamethasone injections, nor was the virus transmitted to these virgin wildebeest and steers which were in pen contact with the affected animals. A domestic bovine heifer developed mild IPV and became a virus carrier, when exposed to the wildebeest IPV virus by vaginal instillation.", "contents": "Observations on the epidemiology of the herpesvirus of infectous bovine rhinotracheitis/infectious pustular vulvovaginitis in wildebeest. Spontaneous vulvovaginitis erupted in wildebeest (Connochaetes taurinus) after betamethasone inoculation. Infectious bovine rhinotracheitis/infectious pustular vulvovaginitis (IBR/IPV) is probably a venereal disease because virgin wildebeest did not develop vulvovaginitis after betamethasone injections, nor was the virus transmitted to these virgin wildebeest and steers which were in pen contact with the affected animals. A domestic bovine heifer developed mild IPV and became a virus carrier, when exposed to the wildebeest IPV virus by vaginal instillation."}
{"id": "PMID:228092", "title": "Susceptibility of mink to certain viral animal diseases foreign to the United States.", "content": "Mink (Mustela vison) were inoculated with viruses: African horse sickness (AHS), African swine fever (ASF), bovine herpes virus II (BHV2), foot-and-mouth disease (FMD), goat pox (GP), hog cholera (HC), peste des petits ruminants (PPR), rinderpest (RP), swine vesicular disease (SVD), vesicular exanthema of swine (VES) and vesicular stomatitis (VS). Their susceptibility was measured by development of clinical signs, virus isolation and detection of precipitin and/or virus neutralizing antibodies. SVD virus produced a lesion in one mink. Virus was isolated from mink inoculated with SVD, FMD and BHV2. Neutralizing and/or precipitin antibodies were detected in mink inoculated with ASF, FMD, GP, RP, SVD and VS viruses. Mink were not susceptible to AHS, HC, PPR and VES viruses.", "contents": "Susceptibility of mink to certain viral animal diseases foreign to the United States. Mink (Mustela vison) were inoculated with viruses: African horse sickness (AHS), African swine fever (ASF), bovine herpes virus II (BHV2), foot-and-mouth disease (FMD), goat pox (GP), hog cholera (HC), peste des petits ruminants (PPR), rinderpest (RP), swine vesicular disease (SVD), vesicular exanthema of swine (VES) and vesicular stomatitis (VS). Their susceptibility was measured by development of clinical signs, virus isolation and detection of precipitin and/or virus neutralizing antibodies. SVD virus produced a lesion in one mink. Virus was isolated from mink inoculated with SVD, FMD and BHV2. Neutralizing and/or precipitin antibodies were detected in mink inoculated with ASF, FMD, GP, RP, SVD and VS viruses. Mink were not susceptible to AHS, HC, PPR and VES viruses."}
{"id": "PMID:228093", "title": "Systemic absorption and sustained effects of vaginal estrogen creams.", "content": "Systemic absorption and sustained effects of two estrogen vaginal cream preparations (Premarin and Estrace) were measured in 29 postmenopausal women receiving daily applications. With both preparations, vaginal absorption of estrogens into the systemic circulation was rapid, efficient, and sustained. It is apparent that estrogen vaginal cream preparations, as widely used in clinical practice for their local effects on the vaginal mucosa, actually result in sustained high estrogen levels in the systemic circulation. The vaginal route shows promise when systemic estrogen therapy is indicated, but is dangerous when estrogen is contraindicated.", "contents": "Systemic absorption and sustained effects of vaginal estrogen creams. Systemic absorption and sustained effects of two estrogen vaginal cream preparations (Premarin and Estrace) were measured in 29 postmenopausal women receiving daily applications. With both preparations, vaginal absorption of estrogens into the systemic circulation was rapid, efficient, and sustained. It is apparent that estrogen vaginal cream preparations, as widely used in clinical practice for their local effects on the vaginal mucosa, actually result in sustained high estrogen levels in the systemic circulation. The vaginal route shows promise when systemic estrogen therapy is indicated, but is dangerous when estrogen is contraindicated."}
{"id": "PMID:228095", "title": "Release of tonin by rat submaxillary gland slices in vitro.", "content": "The effects of isoproterenol, dibutyryl cyclic AMP, theophylline, and angiotensin II upon tonin release were examined by incubation of rat submaximllary gland slices. Isoproterenol, dibutyryl cyclic AMP, and theophylline stimulated tonin release. Propranolol inhibited the effect of isoproterenol. Angiotensin II by itself did not inhibit tonin release, but it suppressed the increase in tonin release produced by isoproterenol. These results suggest that the tonin stimulating effect of isoproterenol is due, at least in part, to a direct stimulation of beta-receptor upon the submaxillary glands and that cyclic AMP system may play a role as an intracellular mediator of this action. Angiotensin II, which is formed directly from a natural protein substrate by tonin, is suggested to inhibit tonin sectetion in some situations.", "contents": "Release of tonin by rat submaxillary gland slices in vitro. The effects of isoproterenol, dibutyryl cyclic AMP, theophylline, and angiotensin II upon tonin release were examined by incubation of rat submaximllary gland slices. Isoproterenol, dibutyryl cyclic AMP, and theophylline stimulated tonin release. Propranolol inhibited the effect of isoproterenol. Angiotensin II by itself did not inhibit tonin release, but it suppressed the increase in tonin release produced by isoproterenol. These results suggest that the tonin stimulating effect of isoproterenol is due, at least in part, to a direct stimulation of beta-receptor upon the submaxillary glands and that cyclic AMP system may play a role as an intracellular mediator of this action. Angiotensin II, which is formed directly from a natural protein substrate by tonin, is suggested to inhibit tonin sectetion in some situations."}
{"id": "PMID:228097", "title": "[Clinical studies on pivmecillinam in urinary tract infections (author's transl)].", "content": "Pivmecillinam (PMPC), semisynthetic penicillin for oral use, was studied clinically and following results were obtained. 1) Twenty-eight patients with acute simple cystitis treated with the drug 200 mg/day for 4 days, clinical results were excellent in 23 cases and moderate in 5 cases. Six patients with chronic simple cystitis treated with the drug 400 mg/day for 7 days, clinical results were excellent in 4 cases, moderate in 1 case and poor in 1 case. Eight patients with complicated urinary tract infections treated with the drug 400 mg/day for 7 days, clinical results were excellent in 2 cases, moderate in 2 cases and poor in 4 cases. Overall effectiveness amounted to 88.1%. 2) Pivmecillinam was clinically effective in patients infected by Gram-negative bacteria except Pseudomonas aeruginosa. 3) No side effects were observed in all cases. The effectiveness of PMPC for acute simple cystitis was compared with that of talampicillin (TAPC), ampicillin (ABPC), amoxicillin (AMPC) and pivampicillin (PVPC) reported previously and PMPC was assessed as the most useful agent in these. Then, pivmecillinam should be chosen firstly as a chemotherapeutic agent for acute simple cystitis.", "contents": "[Clinical studies on pivmecillinam in urinary tract infections (author's transl)]. Pivmecillinam (PMPC), semisynthetic penicillin for oral use, was studied clinically and following results were obtained. 1) Twenty-eight patients with acute simple cystitis treated with the drug 200 mg/day for 4 days, clinical results were excellent in 23 cases and moderate in 5 cases. Six patients with chronic simple cystitis treated with the drug 400 mg/day for 7 days, clinical results were excellent in 4 cases, moderate in 1 case and poor in 1 case. Eight patients with complicated urinary tract infections treated with the drug 400 mg/day for 7 days, clinical results were excellent in 2 cases, moderate in 2 cases and poor in 4 cases. Overall effectiveness amounted to 88.1%. 2) Pivmecillinam was clinically effective in patients infected by Gram-negative bacteria except Pseudomonas aeruginosa. 3) No side effects were observed in all cases. The effectiveness of PMPC for acute simple cystitis was compared with that of talampicillin (TAPC), ampicillin (ABPC), amoxicillin (AMPC) and pivampicillin (PVPC) reported previously and PMPC was assessed as the most useful agent in these. Then, pivmecillinam should be chosen firstly as a chemotherapeutic agent for acute simple cystitis."}
{"id": "PMID:228102", "title": "Glycolipids in human lung carcinoma of histologically different types.", "content": "Glycolipids were isolated from primary human lung carcinoma tissue of various histologic types: adenocarcinoma, squamous cell carcinoma, and undifferentiated small cell carcinoma. Each type of carcinoma had a characteristic glycolipid pattern. The major glycolipids isolated were ceramide monohexosides, ceramide dihexosides, ceramide trihexosides, globoside, and hematoside. Squamous cell carcinoma and undifferentiated small cell carcinoma showed marked increases of ceramide monohexosides and dihexosides. Adenocarcinoma had a much higher level of the sulfatide (ceramide 3-sulfate-galactoside) as compared to squamous cell carcinoma, undifferentiated small cell carcinoma, or normal lung tissue. Embryonic tissue had more significant levels of sulfatide than did the other carcinomas. Adenocarcinoma had significantly lower levels of glycolipids due mainly to a decrease in the amount of ceramide monohexosides and dihexosides and hematoside.", "contents": "Glycolipids in human lung carcinoma of histologically different types. Glycolipids were isolated from primary human lung carcinoma tissue of various histologic types: adenocarcinoma, squamous cell carcinoma, and undifferentiated small cell carcinoma. Each type of carcinoma had a characteristic glycolipid pattern. The major glycolipids isolated were ceramide monohexosides, ceramide dihexosides, ceramide trihexosides, globoside, and hematoside. Squamous cell carcinoma and undifferentiated small cell carcinoma showed marked increases of ceramide monohexosides and dihexosides. Adenocarcinoma had a much higher level of the sulfatide (ceramide 3-sulfate-galactoside) as compared to squamous cell carcinoma, undifferentiated small cell carcinoma, or normal lung tissue. Embryonic tissue had more significant levels of sulfatide than did the other carcinomas. Adenocarcinoma had significantly lower levels of glycolipids due mainly to a decrease in the amount of ceramide monohexosides and dihexosides and hematoside."}
{"id": "PMID:228103", "title": "Susceptibility of human cell lines to feline leukemia virus and feline sarcoma virus.", "content": "The susceptibility of human fibroblasts and human lymphoid cell lines to feline leukemia virus (FeLV) and feline sarcoma virus (FeSV) was investigated. Human cells were highly sensitive to infection by FeLV subgroups B and C and FeSV but resistant to infection by FeLV subgroup A. The cells became infected, produced infectious virus, and displayed no differences in morphology or viability. T-cell lines appeared to be more sensitive to FeLV and FeSV infection and to produce more virus than did autochthonous B-cells. B-cell lines with membrane IgG appeared more resistant to infection than did those with no membrane IgG.", "contents": "Susceptibility of human cell lines to feline leukemia virus and feline sarcoma virus. The susceptibility of human fibroblasts and human lymphoid cell lines to feline leukemia virus (FeLV) and feline sarcoma virus (FeSV) was investigated. Human cells were highly sensitive to infection by FeLV subgroups B and C and FeSV but resistant to infection by FeLV subgroup A. The cells became infected, produced infectious virus, and displayed no differences in morphology or viability. T-cell lines appeared to be more sensitive to FeLV and FeSV infection and to produce more virus than did autochthonous B-cells. B-cell lines with membrane IgG appeared more resistant to infection than did those with no membrane IgG."}
{"id": "PMID:228104", "title": "Improved method for cytogenetic studies of solid tumors.", "content": "Solid human tumors were dissociated with collagenase, cultured for 16-48 hours, and harvested for cytogenetic preparation. Of the 19 tumors used, 14 showed sufficient numbers of metaphases to be useful for chromosome analysis.", "contents": "Improved method for cytogenetic studies of solid tumors. Solid human tumors were dissociated with collagenase, cultured for 16-48 hours, and harvested for cytogenetic preparation. Of the 19 tumors used, 14 showed sufficient numbers of metaphases to be useful for chromosome analysis."}
{"id": "PMID:228105", "title": "Suppression of the immune response in tumor-bearing mice. I. Response to virus-producing tumor cells and non-virus-producing tumor cells.", "content": "Spleen cells from mice inoculated with syngeneic murine sarcoma virus (MuSV)-transformed tumor cells suppressed the mixed leukocyte reaction. Mice inoculated with virus-producing tumor cells demonstrated two types of suppression. First, an early suppression was shown to be mediated by an adherent suppressor T-cell on the basis of its sensitivity to Thy 1.2 antiserum plus complement and the absence of the early suppression in T-cell-deficient nude mice. This suppression may have been induced in response to viral antigens associated with cell surface antigens (modified self-antigens) or viremia, because it was not induced by a non-virus-producing tumor cell line. Second, a late suppression was also seen in tumor-bearing BALB/c mice. This suppression was shown to be T-cell-independent by its presence in nude mice and by its resistance to gamma-irradiation and Thy 1.2 antiserum plus complement. In addition, the late suppression was present in mice inoculated with a nonproducer clone of MuSV-transformed cells. This finding suggests that viral antigens and/or viremia is not required for induction of the late suppression.", "contents": "Suppression of the immune response in tumor-bearing mice. I. Response to virus-producing tumor cells and non-virus-producing tumor cells. Spleen cells from mice inoculated with syngeneic murine sarcoma virus (MuSV)-transformed tumor cells suppressed the mixed leukocyte reaction. Mice inoculated with virus-producing tumor cells demonstrated two types of suppression. First, an early suppression was shown to be mediated by an adherent suppressor T-cell on the basis of its sensitivity to Thy 1.2 antiserum plus complement and the absence of the early suppression in T-cell-deficient nude mice. This suppression may have been induced in response to viral antigens associated with cell surface antigens (modified self-antigens) or viremia, because it was not induced by a non-virus-producing tumor cell line. Second, a late suppression was also seen in tumor-bearing BALB/c mice. This suppression was shown to be T-cell-independent by its presence in nude mice and by its resistance to gamma-irradiation and Thy 1.2 antiserum plus complement. In addition, the late suppression was present in mice inoculated with a nonproducer clone of MuSV-transformed cells. This finding suggests that viral antigens and/or viremia is not required for induction of the late suppression."}
{"id": "PMID:228106", "title": "Suppression of the immune response in tumor-bearing mice. II. Characterization of adherent suppressor cells.", "content": "Adherent spleen cells from late (greater than or equal to 18 days post inoculation) tumor-bearing BALB/c mice suppressed lymphoproliferative and effector immunity as evaluated by the mixed leukocyte culture and cell-mediated lympholysis assays. Procedures that eliminated T-cells or B-cells while enriching for macrophage populations significantly augmented the suppression, whereas removal of phagocytic and adherent cells abrogated the suppressive effect. We concluded that the cells responsible for suppression of cell-mediated immune responses in late tumor-bearing mice were of the monocyte-macrophage series. Furthermore, the suppressive influence was not due merely to the increased number of macrophages in tumor-bearing animals. Experiments clearly showed that the splenic macrophages, even at low concentrations, demonstrated a suppressive function.", "contents": "Suppression of the immune response in tumor-bearing mice. II. Characterization of adherent suppressor cells. Adherent spleen cells from late (greater than or equal to 18 days post inoculation) tumor-bearing BALB/c mice suppressed lymphoproliferative and effector immunity as evaluated by the mixed leukocyte culture and cell-mediated lympholysis assays. Procedures that eliminated T-cells or B-cells while enriching for macrophage populations significantly augmented the suppression, whereas removal of phagocytic and adherent cells abrogated the suppressive effect. We concluded that the cells responsible for suppression of cell-mediated immune responses in late tumor-bearing mice were of the monocyte-macrophage series. Furthermore, the suppressive influence was not due merely to the increased number of macrophages in tumor-bearing animals. Experiments clearly showed that the splenic macrophages, even at low concentrations, demonstrated a suppressive function."}
{"id": "PMID:228107", "title": "Inhibitory effects of macrophages against Marek's disease virus plaque formation in chicken kidney cell cultures.", "content": "Inhibition of plaque formation by Marek's disease virus (MDV) in chicken kidney cell cultures was investigated with the use of peritoneal exudate cells (PEC) from chickens. PEC from MDV-infected White Leghorn chickens inhibited the formation of MDV plaques, whereas the inhibitory effect of PEC from chickens vaccinated with herpesvirus of turkey (HVT) or PEC from normal chickens was very weak. However, PEC from either normal chickens or HVT-vaccinated chickens inhibited the MDV plaque formation in the presence of serum from MDV-infected chickens but not from normal or HVT-vaccinated chickens. The capacity of PEC to inhibit plaque formation was significantly reduced when PEC was treated with carrageenan but not with antithymus or antibursa cell serum. These results indicate that macrophages may have a role in protection against Marek's disease by reducing the number of MDV-infected cells and thereby decreasing the spread of the virus in vivo.", "contents": "Inhibitory effects of macrophages against Marek's disease virus plaque formation in chicken kidney cell cultures. Inhibition of plaque formation by Marek's disease virus (MDV) in chicken kidney cell cultures was investigated with the use of peritoneal exudate cells (PEC) from chickens. PEC from MDV-infected White Leghorn chickens inhibited the formation of MDV plaques, whereas the inhibitory effect of PEC from chickens vaccinated with herpesvirus of turkey (HVT) or PEC from normal chickens was very weak. However, PEC from either normal chickens or HVT-vaccinated chickens inhibited the MDV plaque formation in the presence of serum from MDV-infected chickens but not from normal or HVT-vaccinated chickens. The capacity of PEC to inhibit plaque formation was significantly reduced when PEC was treated with carrageenan but not with antithymus or antibursa cell serum. These results indicate that macrophages may have a role in protection against Marek's disease by reducing the number of MDV-infected cells and thereby decreasing the spread of the virus in vivo."}
{"id": "PMID:228112", "title": "Delayed-type skin hypersensitivity reaction (DTH) to Thomsen-Friedenreich (T) antigen as diagnostic test for human breast adenocarcinoma.", "content": "One intradermal (i.d.) injection of human erythrocyte T antigen in the upper outer arm contralateral to any breast lesion elicits a delayed tuberculin-type hypersensitivity reaction (DTH) in breast carcinoma patients. It is necessary to inject simultaneously but separately the same quantity of MN antigen (about 6--8 cm apart), from which the T Antigen has been prepared, since particularly patients with Stage I breast carcinoma (Internatl. nomenclature) and those with benign breast disease may significantly react to it. The extent of reaction to MN antigen must be subtracted from the reaction to T antigen before interpreting results. DTH response to T antigen was 85% accurate among 67 patients with ductal breast carcinoma of all Stages (including non-invasive), 95% accurate (5% so far falsely positive) among 95 patients with benign breast disease and it was 100% accurate (no false positives) among 36 \"healthy\" persons tested. Among 18 patients with the comparatively rare and less ominous lobular and tubular breast carcinomata, the DTH reaction was positive in 8 of 16 (50%) patients with lobular, and in none of 2 patients with tubular breast carcinoma.", "contents": "Delayed-type skin hypersensitivity reaction (DTH) to Thomsen-Friedenreich (T) antigen as diagnostic test for human breast adenocarcinoma. One intradermal (i.d.) injection of human erythrocyte T antigen in the upper outer arm contralateral to any breast lesion elicits a delayed tuberculin-type hypersensitivity reaction (DTH) in breast carcinoma patients. It is necessary to inject simultaneously but separately the same quantity of MN antigen (about 6--8 cm apart), from which the T Antigen has been prepared, since particularly patients with Stage I breast carcinoma (Internatl. nomenclature) and those with benign breast disease may significantly react to it. The extent of reaction to MN antigen must be subtracted from the reaction to T antigen before interpreting results. DTH response to T antigen was 85% accurate among 67 patients with ductal breast carcinoma of all Stages (including non-invasive), 95% accurate (5% so far falsely positive) among 95 patients with benign breast disease and it was 100% accurate (no false positives) among 36 \"healthy\" persons tested. Among 18 patients with the comparatively rare and less ominous lobular and tubular breast carcinomata, the DTH reaction was positive in 8 of 16 (50%) patients with lobular, and in none of 2 patients with tubular breast carcinoma."}
{"id": "PMID:228114", "title": "Spontaneous cholangiocarcinoma in a ring-tailed lemur (Lemur catta).", "content": "A cholangiocarcinoma in the liver with metastasis to the regional lymph nodes was found in a male ring-tailed lemur (Lemur catta). The liver was partially replaced by a gray-white, coarsely lobulated mass. Microscopically, the tumor consisted of well circumscribed lobules of anaplastic, low cuboidal cells occasionally arranged in duct-like structures. The tumor did not involve the gallbladder.", "contents": "Spontaneous cholangiocarcinoma in a ring-tailed lemur (Lemur catta). A cholangiocarcinoma in the liver with metastasis to the regional lymph nodes was found in a male ring-tailed lemur (Lemur catta). The liver was partially replaced by a gray-white, coarsely lobulated mass. Microscopically, the tumor consisted of well circumscribed lobules of anaplastic, low cuboidal cells occasionally arranged in duct-like structures. The tumor did not involve the gallbladder."}
{"id": "PMID:228115", "title": "Three types of Auer bodies in acute leukemia. Visualization of their protein by negative contrast after peroxidase cytochemistry.", "content": "Ten cases of acute granulocytic leukemia with blast cells containing Auer bodies (ABs) have been studied by electron microscopy after cytochemical demonstration of myeloperoxidase. The cytochemical dense reaction product has been used as a dark field to visualize unreactive protein of ABs which may then be easily identified by its negative contrast. This method has allowed us to identify three types of ABs which differ in their substructure. In type I, (five patients with promyelocytic leukemia), our study confirmed that all of the ABs consisted of a hexagonal arrangement of hollow tubes. Cells from four cases of acute myeloblastic leukemia displayed type II ABs, in which a unique pattern of protein associated in a regular linear arrangement with well defined periodicity was identified. Type III appeared characteristic of a subclass of acute myeloblastic leukemia in which large inclusions with Chediak-Higashi-like granules containing numerous micro-ABs were seen. The configuration, size, and organization of the protein in the crystal were distinct from those seen in the two other types of ABs. These features suggest that the nature of the protein in ABs may be heterogeneous.", "contents": "Three types of Auer bodies in acute leukemia. Visualization of their protein by negative contrast after peroxidase cytochemistry. Ten cases of acute granulocytic leukemia with blast cells containing Auer bodies (ABs) have been studied by electron microscopy after cytochemical demonstration of myeloperoxidase. The cytochemical dense reaction product has been used as a dark field to visualize unreactive protein of ABs which may then be easily identified by its negative contrast. This method has allowed us to identify three types of ABs which differ in their substructure. In type I, (five patients with promyelocytic leukemia), our study confirmed that all of the ABs consisted of a hexagonal arrangement of hollow tubes. Cells from four cases of acute myeloblastic leukemia displayed type II ABs, in which a unique pattern of protein associated in a regular linear arrangement with well defined periodicity was identified. Type III appeared characteristic of a subclass of acute myeloblastic leukemia in which large inclusions with Chediak-Higashi-like granules containing numerous micro-ABs were seen. The configuration, size, and organization of the protein in the crystal were distinct from those seen in the two other types of ABs. These features suggest that the nature of the protein in ABs may be heterogeneous."}
{"id": "PMID:228116", "title": "Pulmonary oat cell carcinomas. Expression of plasma membrane antigen correlated with presence of cytoplasmic neurosecretory granules.", "content": "A plasma membrane antigen highly associated with pulmonary oat cell carcinoma has recently been identified. Expression of this surface antigen was now examined in routine surgical pathology material from 32 primary lung tumors by immunostaining. The staining patterns of 17 tumors diagnosed as oat cell carcinoma by light microscopy were compared to those of 10 epidermoid carcinomas, four carcinoid tumors, and one lymphocytic lymphoma. In addition, when available, the oat cell carcinoma group was also studied by electron microscopy for demonstration of cytoplasmic neurosecretory granules. Twelve of the 17 oat cell carcinomas and one of the epidermoid carcinomas expressed the antigen. In this group of small cell tumors of the lung, aggrement was found between the expression of this immunochemical marker and the presence of neurosecretory granules in the cytoplasm of the tumors. Demonstration of this surface antigen in routine surgical pathologic material may be a useful aid in the diagnosis of these tumors. The failure of a group of tumors, which satisfied the light microscopic criteria for oat cell carcinoma to stain for the antigen, demonstrates heterogeneity within the oat cell carcinoma group.", "contents": "Pulmonary oat cell carcinomas. Expression of plasma membrane antigen correlated with presence of cytoplasmic neurosecretory granules. A plasma membrane antigen highly associated with pulmonary oat cell carcinoma has recently been identified. Expression of this surface antigen was now examined in routine surgical pathology material from 32 primary lung tumors by immunostaining. The staining patterns of 17 tumors diagnosed as oat cell carcinoma by light microscopy were compared to those of 10 epidermoid carcinomas, four carcinoid tumors, and one lymphocytic lymphoma. In addition, when available, the oat cell carcinoma group was also studied by electron microscopy for demonstration of cytoplasmic neurosecretory granules. Twelve of the 17 oat cell carcinomas and one of the epidermoid carcinomas expressed the antigen. In this group of small cell tumors of the lung, aggrement was found between the expression of this immunochemical marker and the presence of neurosecretory granules in the cytoplasm of the tumors. Demonstration of this surface antigen in routine surgical pathologic material may be a useful aid in the diagnosis of these tumors. The failure of a group of tumors, which satisfied the light microscopic criteria for oat cell carcinoma to stain for the antigen, demonstrates heterogeneity within the oat cell carcinoma group."}
{"id": "PMID:228118", "title": "Progressive hearing impairment in children with congenital cytomegalovirus infection.", "content": "Audiological assessment of 86 children with congenital cytomegalovirus infection revealed progressive hearing loss in four of 12 subjects with sensorineural hearing impairments. Case descriptions are presented documenting the progression of the hearing loss. In view of the findings, children with congenital cytomegalovirus should be monitored closely to insure detection of possible delayed or progressive hearing impairment and delivery of appropriate habilitative services.", "contents": "Progressive hearing impairment in children with congenital cytomegalovirus infection. Audiological assessment of 86 children with congenital cytomegalovirus infection revealed progressive hearing loss in four of 12 subjects with sensorineural hearing impairments. Case descriptions are presented documenting the progression of the hearing loss. In view of the findings, children with congenital cytomegalovirus should be monitored closely to insure detection of possible delayed or progressive hearing impairment and delivery of appropriate habilitative services."}
{"id": "PMID:228121", "title": "Solitary multinodular giant cell tumor of tendon sheath.", "content": "We present a 74 year old man with a solitary multinodular tumor of the right thumb and an adenocarcinoma of the prostate. Histologic examination of the hand tumor revealed a giant cell tumor of tendon sheath.", "contents": "Solitary multinodular giant cell tumor of tendon sheath. We present a 74 year old man with a solitary multinodular tumor of the right thumb and an adenocarcinoma of the prostate. Histologic examination of the hand tumor revealed a giant cell tumor of tendon sheath."}
{"id": "PMID:228122", "title": "Prognostic value of pre-treatment lymphocyte count and T cell levels in localized bronchogenic carcinoma.", "content": "In the patient with clinically localized bronchogenic carcinoma, the pre-treatment peripheral blood lymphocyte count and the thymus-dependent lymphocyte (T cell) level correlated with the prognosis of the tumor histology was either squamous cell, oat cell, or undifferentiated carcinoma. Patients whose pre-treatment lymphocyte count was less than 1,000/ml or whose T cell level was less than 750/ml either died or developed distant metastases by nine months after treatment of their localized tumor. By contrast, 55% of patients whose pre-treatment T cell level was greater than 750/ml were alive and without evidence of metastases nine months after treatment (P less than 0.02). Analysis of survival of these patients by the life-table method through the first post-treatment year further demonstrates the prognostic value of a low pre-treatment lymphocyte count or T cell level. The pre-treatment lymphocyte count and T cell level in patients with adenocarcinoma did not correlate with prognosis.", "contents": "Prognostic value of pre-treatment lymphocyte count and T cell levels in localized bronchogenic carcinoma. In the patient with clinically localized bronchogenic carcinoma, the pre-treatment peripheral blood lymphocyte count and the thymus-dependent lymphocyte (T cell) level correlated with the prognosis of the tumor histology was either squamous cell, oat cell, or undifferentiated carcinoma. Patients whose pre-treatment lymphocyte count was less than 1,000/ml or whose T cell level was less than 750/ml either died or developed distant metastases by nine months after treatment of their localized tumor. By contrast, 55% of patients whose pre-treatment T cell level was greater than 750/ml were alive and without evidence of metastases nine months after treatment (P less than 0.02). Analysis of survival of these patients by the life-table method through the first post-treatment year further demonstrates the prognostic value of a low pre-treatment lymphocyte count or T cell level. The pre-treatment lymphocyte count and T cell level in patients with adenocarcinoma did not correlate with prognosis."}
{"id": "PMID:228123", "title": "5-FU versus combination therapy with tubercidin, streptozotocin, and 5-FU in the treatment of pancreatic carcinomas: COG protocol 7230.", "content": "From May 1972 until May 1976, 105 patients were entered on Central Oncology Group protocol 7230 to compare the combination of streptozotocin, tubercidin, and 5-fluorouracil (5-FU) versus 5-FU alone in the treatment of adenocarcinoma and islet cell carcinoma of the pancreas. Twenty-nine were not evaluable. Thirty-six evaluable cases received 5-FU, and 40 received the combination, with no significant difference in time to progression or survival. Toxicity in the two regimens was somewhat different but was essentially similar in magnitude. Results indicate no benefit in the treatment of adenocarcinoma of the pancreas with the three-drug combination over 5-FU alone. All of the islet cell tumor patients benefited from the combination by response or arrest of progression of disease. Further study should be directed toward the use of this combination in the treatment of functioning and non-functioning islet cell tumors of the pancreas.", "contents": "5-FU versus combination therapy with tubercidin, streptozotocin, and 5-FU in the treatment of pancreatic carcinomas: COG protocol 7230. From May 1972 until May 1976, 105 patients were entered on Central Oncology Group protocol 7230 to compare the combination of streptozotocin, tubercidin, and 5-fluorouracil (5-FU) versus 5-FU alone in the treatment of adenocarcinoma and islet cell carcinoma of the pancreas. Twenty-nine were not evaluable. Thirty-six evaluable cases received 5-FU, and 40 received the combination, with no significant difference in time to progression or survival. Toxicity in the two regimens was somewhat different but was essentially similar in magnitude. Results indicate no benefit in the treatment of adenocarcinoma of the pancreas with the three-drug combination over 5-FU alone. All of the islet cell tumor patients benefited from the combination by response or arrest of progression of disease. Further study should be directed toward the use of this combination in the treatment of functioning and non-functioning islet cell tumors of the pancreas."}
{"id": "PMID:228125", "title": "Sleeve lobectomy for carcinoma of the lung.", "content": "Sleeve lobectomy for non-oat cell carcinoma involving a major bronchus preserves functioning lung tissue and, in carefully selected patients, provides long-term survival comparable to pneumonectomy. Seventy patients underwent sleeve lobectomy between 1967 and 1978. Twenty-seven patients were considered compromised (Group I) because they had severe respiratory impairment which contraindicated pneumonectomy. Forty-three patients were considered uncompromised (Group 2) and underwent elective sleeve lobectomy. Seventy patients with a similar non-oat cell carcinoma involving the proximal bronchi underwent pneumonectomy (Group 3) during this period. Perioperative complications occurred more frequently in Group 1 (59%) than in Group 2 (21%) or Group 3 (23%). Both periopeative mortality rate and the incidence of bronchial disruption (bronchovascular and bronchopleural fistulas) were higher in Group I (19% and 22%) than in Group 2 (9% and 5%) or Group 3 (3% and 7%). Survival depended primarily on the surgeon's ability to perform a complete resection of the tumor. An incomplete resection resulted when tumor was found in the highest lymph node or in the last bronchial resection margin when paraffin sections were reviewed. The 5 year survival rate was 18% for compromised patients (Group 1) who underwent complete resection, and there  were no survivors among patients undergoing incomplete resections. Uncompromised patients ( Group 2) had a 5 year survival rate of36% with complete and 12% with incomplete resections. Pneumonectomy patients (Group 3) had a 64% 5 year survival rate with a complete resection and 16% with an incomplete resection. The stage of the disease at the time of operation had a profound effect on the survivail. There was no difference inthe 5 and 8 year survival rates between uncompromised patients undergoing sleeve resection ( Group 2) and patients undergoing peneumonectomy (Group 3) for comparable stage of their disease. A careful pre- and postoperative functional assessment revealed that pulmonary performance was improved in 44% of Group 1, 63% of Group 2, and only 14% of Group 3 patients. Patients wiht impaired pulmonary reserve underwent sleeve lobectomy with an adequate disease-free interval when complete tumor excision was possible. Uncompromised patients whose extensive disease required incomplete resection had palliation by sleeve lobectomy equivalent to that by pneumonectomy. When complete t-mor resection was possible, patients with uncompromised pulmonary reserve had a perioperative complication rate and long-term survival equivalent to that of pneumonectomy while preserving pulmonary parenchyma, which permitted an improvement in postoperative pulmonary performance.", "contents": "Sleeve lobectomy for carcinoma of the lung. Sleeve lobectomy for non-oat cell carcinoma involving a major bronchus preserves functioning lung tissue and, in carefully selected patients, provides long-term survival comparable to pneumonectomy. Seventy patients underwent sleeve lobectomy between 1967 and 1978. Twenty-seven patients were considered compromised (Group I) because they had severe respiratory impairment which contraindicated pneumonectomy. Forty-three patients were considered uncompromised (Group 2) and underwent elective sleeve lobectomy. Seventy patients with a similar non-oat cell carcinoma involving the proximal bronchi underwent pneumonectomy (Group 3) during this period. Perioperative complications occurred more frequently in Group 1 (59%) than in Group 2 (21%) or Group 3 (23%). Both periopeative mortality rate and the incidence of bronchial disruption (bronchovascular and bronchopleural fistulas) were higher in Group I (19% and 22%) than in Group 2 (9% and 5%) or Group 3 (3% and 7%). Survival depended primarily on the surgeon's ability to perform a complete resection of the tumor. An incomplete resection resulted when tumor was found in the highest lymph node or in the last bronchial resection margin when paraffin sections were reviewed. The 5 year survival rate was 18% for compromised patients (Group 1) who underwent complete resection, and there  were no survivors among patients undergoing incomplete resections. Uncompromised patients ( Group 2) had a 5 year survival rate of36% with complete and 12% with incomplete resections. Pneumonectomy patients (Group 3) had a 64% 5 year survival rate with a complete resection and 16% with an incomplete resection. The stage of the disease at the time of operation had a profound effect on the survivail. There was no difference inthe 5 and 8 year survival rates between uncompromised patients undergoing sleeve resection ( Group 2) and patients undergoing peneumonectomy (Group 3) for comparable stage of their disease. A careful pre- and postoperative functional assessment revealed that pulmonary performance was improved in 44% of Group 1, 63% of Group 2, and only 14% of Group 3 patients. Patients wiht impaired pulmonary reserve underwent sleeve lobectomy with an adequate disease-free interval when complete tumor excision was possible. Uncompromised patients whose extensive disease required incomplete resection had palliation by sleeve lobectomy equivalent to that by pneumonectomy. When complete t-mor resection was possible, patients with uncompromised pulmonary reserve had a perioperative complication rate and long-term survival equivalent to that of pneumonectomy while preserving pulmonary parenchyma, which permitted an improvement in postoperative pulmonary performance."}
{"id": "PMID:228127", "title": "Modification of the substrate specificity of rat hepatic lipase by collagenase treatment.", "content": "Collagenase is currently used in the isolation of rat hepatocytes, but it rapidly inactivates the heparin-releasable triacylglycerol lipase of the liver. Since collagenase-isolated liver cells contain a heparin-releasable monoacylglycerol hydrolase, a study was made on the effect of collagenase treatment on the substrate specificity of purified heparin-releasable lipase of rat liver. Incubation of the purified lipase with collagenase selectively decreased the triacylglycerol lipase activity of the enzyme with no effect on the monoacylglycerol hydrolase activity. Gel filtration of the lipase before and after collagenase treatment indicated cleavage of a small molecular weight fragment from the enzyme. This resulted in a preparation with less triacylglycerol lipase activity but still capable of monoacylglycerol hydrolysis.", "contents": "Modification of the substrate specificity of rat hepatic lipase by collagenase treatment. Collagenase is currently used in the isolation of rat hepatocytes, but it rapidly inactivates the heparin-releasable triacylglycerol lipase of the liver. Since collagenase-isolated liver cells contain a heparin-releasable monoacylglycerol hydrolase, a study was made on the effect of collagenase treatment on the substrate specificity of purified heparin-releasable lipase of rat liver. Incubation of the purified lipase with collagenase selectively decreased the triacylglycerol lipase activity of the enzyme with no effect on the monoacylglycerol hydrolase activity. Gel filtration of the lipase before and after collagenase treatment indicated cleavage of a small molecular weight fragment from the enzyme. This resulted in a preparation with less triacylglycerol lipase activity but still capable of monoacylglycerol hydrolysis."}
{"id": "PMID:228132", "title": "Panel discussion: glomus jugulare tumors of the temporal bone. Radiological appearance of glomus tumors.", "content": "Depending upon the stage of pathogenesis, some glomus tumors demonstrate characteristic radiographic findings which permit a presumptive diagnosis of this type of tumor. Three factors are helpful in interpreting multidirectional tomography of the temporal bone when a glomus tumor is suspected. The tumor shows a predilection for bony erosion of the carotid crest and hypotympanum. It tends to destroy bone in its path by small lobulated invasions producing a fairly well demarcated border of crescentic shaped translucencies. In contradistinction to other tumors and infections, glomus tumors tend to spare the lateral wall of the attic and the ossicular chain even when the tumor if fairly well advanced in size.", "contents": "Panel discussion: glomus jugulare tumors of the temporal bone. Radiological appearance of glomus tumors. Depending upon the stage of pathogenesis, some glomus tumors demonstrate characteristic radiographic findings which permit a presumptive diagnosis of this type of tumor. Three factors are helpful in interpreting multidirectional tomography of the temporal bone when a glomus tumor is suspected. The tumor shows a predilection for bony erosion of the carotid crest and hypotympanum. It tends to destroy bone in its path by small lobulated invasions producing a fairly well demarcated border of crescentic shaped translucencies. In contradistinction to other tumors and infections, glomus tumors tend to spare the lateral wall of the attic and the ossicular chain even when the tumor if fairly well advanced in size."}
{"id": "PMID:228133", "title": "Panel discussion: glomus jugulare tumors of the temporal bone. Radiation of glomus tumors of the temporal bone.", "content": "In a study done at the Geisinger Medical Center in 1976, the results of treatment of 30 cases of glomus tumors involving the ear were reviewed. All 8 cases of glomus tympanicum were controlled with surgery and all of the cases of glomus jugulare treated with high voltage radiotherapy were controlled for from 2 to 12 years. Currently, the length of control extends to 15 years and there have been no late recurrences. Three additional cases showing unusual features of glomus jugulare are presented.", "contents": "Panel discussion: glomus jugulare tumors of the temporal bone. Radiation of glomus tumors of the temporal bone. In a study done at the Geisinger Medical Center in 1976, the results of treatment of 30 cases of glomus tumors involving the ear were reviewed. All 8 cases of glomus tympanicum were controlled with surgery and all of the cases of glomus jugulare treated with high voltage radiotherapy were controlled for from 2 to 12 years. Currently, the length of control extends to 15 years and there have been no late recurrences. Three additional cases showing unusual features of glomus jugulare are presented."}
{"id": "PMID:228134", "title": "Panel discussion: glomus jugulare tumors of the temporal bone. Patterns of invasion in the temporal bone.", "content": "The purpose of this paper is to enumerate and define the exact patterns of glomus jugulare tumor invasion in the temporal bone. Special attention will be focused on those pathways which lead to central nervous system (CNS) invasion.", "contents": "Panel discussion: glomus jugulare tumors of the temporal bone. Patterns of invasion in the temporal bone. The purpose of this paper is to enumerate and define the exact patterns of glomus jugulare tumor invasion in the temporal bone. Special attention will be focused on those pathways which lead to central nervous system (CNS) invasion."}
{"id": "PMID:228135", "title": "Panel discussion: glomus jugulare tumors of the temporal bone. The surgical management of glomus tumors.", "content": "The authors describe the diagnosis and surgical management of 70 glomus tumors seen at the Otology Group in an 8 yr. period. The need for bilateral arteriograms to detect associated tumors (carotid body and intervagale) is stressed. A new surgical technique, the modified intratemporal fossa approach, is described for the removal of large glomus jugulare tumors involving the carotid artery. Complications and results are discussed in detail.", "contents": "Panel discussion: glomus jugulare tumors of the temporal bone. The surgical management of glomus tumors. The authors describe the diagnosis and surgical management of 70 glomus tumors seen at the Otology Group in an 8 yr. period. The need for bilateral arteriograms to detect associated tumors (carotid body and intervagale) is stressed. A new surgical technique, the modified intratemporal fossa approach, is described for the removal of large glomus jugulare tumors involving the carotid artery. Complications and results are discussed in detail."}
{"id": "PMID:228136", "title": "Congenital cytomegalovirus and hearing loss: clinical and experimental observations.", "content": "The effects of congenital cytomegalovirus infection vary from severe central nervous system destruction to asymptomatic viuria. Yet children with the latter have a high incidence of unsuspected hearing loss. Histopathology of temporal bones from children who die with cytomegalic inclusion disease shows viral infected cells in non-sensory endolabyrinthine epithelium. Experimental mouse cytomegalovirus causes an age related cranial neuronitis and perilabyrinthitis. Immunopathologic localization of different viral antigens in experimental inner ear infections shows differential vulnerability of labyrinthine structures to infections. Adaptation of such techniques to human temporal bone pathology could yield information regarding pathogenesis of viral labyrinthitis. The development of a human cytomegalovirus vaccine may eliminate the risks of this congenital infection.", "contents": "Congenital cytomegalovirus and hearing loss: clinical and experimental observations. The effects of congenital cytomegalovirus infection vary from severe central nervous system destruction to asymptomatic viuria. Yet children with the latter have a high incidence of unsuspected hearing loss. Histopathology of temporal bones from children who die with cytomegalic inclusion disease shows viral infected cells in non-sensory endolabyrinthine epithelium. Experimental mouse cytomegalovirus causes an age related cranial neuronitis and perilabyrinthitis. Immunopathologic localization of different viral antigens in experimental inner ear infections shows differential vulnerability of labyrinthine structures to infections. Adaptation of such techniques to human temporal bone pathology could yield information regarding pathogenesis of viral labyrinthitis. The development of a human cytomegalovirus vaccine may eliminate the risks of this congenital infection."}
{"id": "PMID:228137", "title": "Autogenous vaccine treatment of juvenile laryngeal papillomatosis.", "content": "Seventeen cases of juvenile laryngeal papillomatosis have been seen and treated with microlaryngoscopy, removal of papillomas, and administering of autogenous vaccine. Holinger's original findings could be confirmed. The operation frequency of 9 patients was significantly reduced, 5 were improved, and 3 unchanged. In no case was an undesirable reaction to the vaccine observed. Electron microscopy showed no virus-like particles in the papilloma but a section of a vulvar wart did show the virus.", "contents": "Autogenous vaccine treatment of juvenile laryngeal papillomatosis. Seventeen cases of juvenile laryngeal papillomatosis have been seen and treated with microlaryngoscopy, removal of papillomas, and administering of autogenous vaccine. Holinger's original findings could be confirmed. The operation frequency of 9 patients was significantly reduced, 5 were improved, and 3 unchanged. In no case was an undesirable reaction to the vaccine observed. Electron microscopy showed no virus-like particles in the papilloma but a section of a vulvar wart did show the virus."}
{"id": "PMID:228138", "title": "Fibrous histiocytoma of the parotid gland.", "content": "Fibrous histiocytomas are not uncommonly found in the head and neck region. These tumors, arising from the tissue histiocyte, generally behave in a benign fashion. An unusual case of a fibrous histiocytoma arising in the parotid gland is presented. The histopathology of these lesions as well as parotid neoplasms in children is reviewed. Wide local excision without sacrifice of important structures is the treatment of choice.", "contents": "Fibrous histiocytoma of the parotid gland. Fibrous histiocytomas are not uncommonly found in the head and neck region. These tumors, arising from the tissue histiocyte, generally behave in a benign fashion. An unusual case of a fibrous histiocytoma arising in the parotid gland is presented. The histopathology of these lesions as well as parotid neoplasms in children is reviewed. Wide local excision without sacrifice of important structures is the treatment of choice."}
{"id": "PMID:228152", "title": "[Determination of free crystalline silica in the dust containing silicates].", "content": "The content of free crystalline silica in dusts containing silicates was investigated using Polezajew's method, the HBF4 method and X-ray diffraction. Polezajew's method was found to give highly increased results (133.4% on the average), and with 5% of quartz in mixture with kaolin--252%. Solution of silicates, when heated, in fluoroboric acid considerably reduces the error of determination. The mean value of SiO2 recovery in mixtures of quartz with kaolin is 102.9% and with 5% of quartz--116. This method is highly precise. The results of determination of crystalline silica content in some mineral raw materials used in ceramic industry approximated the results obtained using X-ray diffraction.", "contents": "[Determination of free crystalline silica in the dust containing silicates]. The content of free crystalline silica in dusts containing silicates was investigated using Polezajew's method, the HBF4 method and X-ray diffraction. Polezajew's method was found to give highly increased results (133.4% on the average), and with 5% of quartz in mixture with kaolin--252%. Solution of silicates, when heated, in fluoroboric acid considerably reduces the error of determination. The mean value of SiO2 recovery in mixtures of quartz with kaolin is 102.9% and with 5% of quartz--116. This method is highly precise. The results of determination of crystalline silica content in some mineral raw materials used in ceramic industry approximated the results obtained using X-ray diffraction."}
{"id": "PMID:228155", "title": "Preparative scale isolation of basal-lateral plasma membranes from rat intestinal epithelial cells.", "content": "A simple, efficient procedure is described for the preparative scale isolation of basal-lateral membranes from the rat intestinal epithelium. The intestinal mucosa was mildly homogenized and soluble protein and RNA were separated from the homogenate by differential centrifugation. The basal-lateral membranes were then separated from nuclei, mitochondria, and brush border membranes by differential centrifugation in a medium close to the equilibrium density of the basal-lateral membranes. Final purification of the basal-lateral membranes was achieved on a linear density gradient in a high-capacity zonal rotor. The final product (usually at least 40 mg protein) represented a 34% yield of basal-lateral membranes purified 18-fold with respect to protein, 26-fold with respect to brush border membranes, and 53-fold with respect to mitochondria.", "contents": "Preparative scale isolation of basal-lateral plasma membranes from rat intestinal epithelial cells. A simple, efficient procedure is described for the preparative scale isolation of basal-lateral membranes from the rat intestinal epithelium. The intestinal mucosa was mildly homogenized and soluble protein and RNA were separated from the homogenate by differential centrifugation. The basal-lateral membranes were then separated from nuclei, mitochondria, and brush border membranes by differential centrifugation in a medium close to the equilibrium density of the basal-lateral membranes. Final purification of the basal-lateral membranes was achieved on a linear density gradient in a high-capacity zonal rotor. The final product (usually at least 40 mg protein) represented a 34% yield of basal-lateral membranes purified 18-fold with respect to protein, 26-fold with respect to brush border membranes, and 53-fold with respect to mitochondria."}
{"id": "PMID:228156", "title": "Stability of rhodopsin in detergent solutions.", "content": "The thermal stability of lipid-free rhodopsin in solutions of a homologous series of alkyltrimethylammonium bromide detergents and one nonionic detergent, dodecyl-beta-maltoside, has been studied as a function of detergent concentration. Rhodopsin thermal stability increases with increasing chain length within the homologous series of ionic detergents, and for chain lengths greater than 10 carbon atoms increases with increasing detergent concentration up to a \"critical\" concentration that depends on the chain length. Stability also increases with increasing detergent concentration for rhodopsin in solutions of the nonionic detergent. These results may be rationalized in terms of the dependence of micelle packing density on the detergent chain length, head group, and concentration.", "contents": "Stability of rhodopsin in detergent solutions. The thermal stability of lipid-free rhodopsin in solutions of a homologous series of alkyltrimethylammonium bromide detergents and one nonionic detergent, dodecyl-beta-maltoside, has been studied as a function of detergent concentration. Rhodopsin thermal stability increases with increasing chain length within the homologous series of ionic detergents, and for chain lengths greater than 10 carbon atoms increases with increasing detergent concentration up to a \"critical\" concentration that depends on the chain length. Stability also increases with increasing detergent concentration for rhodopsin in solutions of the nonionic detergent. These results may be rationalized in terms of the dependence of micelle packing density on the detergent chain length, head group, and concentration."}
{"id": "PMID:228157", "title": "Plasma concentrations of unconjugated and conjugated estrogens and gonadotrophins following application of various estrogen preparations after oophorectomy and in the menopause.", "content": "In 55 patients after oophorectomy and 20 women after natural menopause an oral estrogen replacement therapy was performed with estrone-sulfate, estradiol 17-valerate, estriol-succinate, a combination of micronized estradiol and estriol (Estrifam, Trisequens), and natural conjugated estrogens. In 4 patients a 3 mg estradiol per 5 g ointment substance was applied on the abdominal skin. The interindividual variations of estrogen increments during therapy were considerably high. Oral intake of 2 mg estriol-succinate daily was followed by a 500% increase of total (conjugated + unconjugated) estriol. Concentrations of unconjugated estrogens were not altered by this dosage. Following oral application of the other above mentioned preparations, prominent rises--especially of unconjugated estrogens in plasma--were noted. The concentration peaks occurred within 3--6 h after application. Unconjugated estradiol-17 beta in plasma was comparable with values of the follicular phase of a normal menstrual cycle, unconjugated estrone, however, was nonphysiologically high. Consequently, the E1/E2 ratio was greater than one whereas it is normally below one. 12 h after oral estrogen application, plasma estrogens dropped to almost initial values, so that a second medication seems to be necessary in order to guarantee an adequate supplementation over the course of the day. The hormone values determined in this study did not show significant differences between patients after a natural menopause and after oophorectomy. There was a positive correlation between rising estrogen levels and suppressed gonadotrophins during replacement therapy. The occurrence of climacteric symptoms did not exclusively depend on low estrogen and high gonadotrophin levels. Good tolerance of estrogen therapy with significantly elevated estrogen concentrations in plasma can be obtained transcutaneously in the form of estrogen ointments. Such therapy might simulate the physiological estrogen pattern even better than oral application does because of delayed and diluted steroid flow to the liver.", "contents": "Plasma concentrations of unconjugated and conjugated estrogens and gonadotrophins following application of various estrogen preparations after oophorectomy and in the menopause. In 55 patients after oophorectomy and 20 women after natural menopause an oral estrogen replacement therapy was performed with estrone-sulfate, estradiol 17-valerate, estriol-succinate, a combination of micronized estradiol and estriol (Estrifam, Trisequens), and natural conjugated estrogens. In 4 patients a 3 mg estradiol per 5 g ointment substance was applied on the abdominal skin. The interindividual variations of estrogen increments during therapy were considerably high. Oral intake of 2 mg estriol-succinate daily was followed by a 500% increase of total (conjugated + unconjugated) estriol. Concentrations of unconjugated estrogens were not altered by this dosage. Following oral application of the other above mentioned preparations, prominent rises--especially of unconjugated estrogens in plasma--were noted. The concentration peaks occurred within 3--6 h after application. Unconjugated estradiol-17 beta in plasma was comparable with values of the follicular phase of a normal menstrual cycle, unconjugated estrone, however, was nonphysiologically high. Consequently, the E1/E2 ratio was greater than one whereas it is normally below one. 12 h after oral estrogen application, plasma estrogens dropped to almost initial values, so that a second medication seems to be necessary in order to guarantee an adequate supplementation over the course of the day. The hormone values determined in this study did not show significant differences between patients after a natural menopause and after oophorectomy. There was a positive correlation between rising estrogen levels and suppressed gonadotrophins during replacement therapy. The occurrence of climacteric symptoms did not exclusively depend on low estrogen and high gonadotrophin levels. Good tolerance of estrogen therapy with significantly elevated estrogen concentrations in plasma can be obtained transcutaneously in the form of estrogen ointments. Such therapy might simulate the physiological estrogen pattern even better than oral application does because of delayed and diluted steroid flow to the liver."}
{"id": "PMID:228159", "title": "Seroconversion to human-cytomegalovirus-specific pre-early nuclear antigens in renal transplant recipients.", "content": "Seroconversion to human cytomegalovirus (H-CMV)-specific antigens was observed in 8 out of 9 renal transplant recipients. In 7 of the 8 recipients antibody to \"pre-early nuclear antigens\" (PENA), which are detectable in human embryonic lung cells within 1 hr of H-CMV infection by anti-complement immunofluorescence staining, developed concomitantly with the increase in other antibodies including anti-early antigens (EA), anti-nuclear inclusions (NI), and complement-fixing (CF) antibody in 1--2 months after transplantation. About 1 year later, anti-PENA and anti-EA titers were concomitantly decreased in 2 recipients, whereas anti-NI and CF antibody titers were maintained at elevated levels in all the seroconverted recipients. These results support the idea that the development of antibody to PENA, like antibody to EA, may represent a current or recent infection with (or reactivation of) H-CMV. In one patient, antibody to PENA did not develop through the observation period despite increases in antibody to EA and other antibodies; this lends support to immunological distinctness of PENA from EA.", "contents": "Seroconversion to human-cytomegalovirus-specific pre-early nuclear antigens in renal transplant recipients. Seroconversion to human cytomegalovirus (H-CMV)-specific antigens was observed in 8 out of 9 renal transplant recipients. In 7 of the 8 recipients antibody to \"pre-early nuclear antigens\" (PENA), which are detectable in human embryonic lung cells within 1 hr of H-CMV infection by anti-complement immunofluorescence staining, developed concomitantly with the increase in other antibodies including anti-early antigens (EA), anti-nuclear inclusions (NI), and complement-fixing (CF) antibody in 1--2 months after transplantation. About 1 year later, anti-PENA and anti-EA titers were concomitantly decreased in 2 recipients, whereas anti-NI and CF antibody titers were maintained at elevated levels in all the seroconverted recipients. These results support the idea that the development of antibody to PENA, like antibody to EA, may represent a current or recent infection with (or reactivation of) H-CMV. In one patient, antibody to PENA did not develop through the observation period despite increases in antibody to EA and other antibodies; this lends support to immunological distinctness of PENA from EA."}
{"id": "PMID:228161", "title": "Interaction between 30 S ribosomal components in a viomycin resistant mutant of Mycobacterium smegmatis.", "content": "A high level viomycin resistant mutant of Mycobacterium smegmatis ATCC 14468 (AC16) was analyzed genetically and biochemically in an attempt to understand the mechanisms of expression of high level viomycin resistance and co-resistance to kanamycin and streptomycin. Genetic analysis has shown that at least three different genes (vicC, str, and kan) were involved in the phenotypic expression of drug resistance in AC16, and high level resistance to viomycin was due to interactions between the products of these genes.", "contents": "Interaction between 30 S ribosomal components in a viomycin resistant mutant of Mycobacterium smegmatis. A high level viomycin resistant mutant of Mycobacterium smegmatis ATCC 14468 (AC16) was analyzed genetically and biochemically in an attempt to understand the mechanisms of expression of high level viomycin resistance and co-resistance to kanamycin and streptomycin. Genetic analysis has shown that at least three different genes (vicC, str, and kan) were involved in the phenotypic expression of drug resistance in AC16, and high level resistance to viomycin was due to interactions between the products of these genes."}
{"id": "PMID:228163", "title": "Characterization of bovine parainfluenza virus type 3.", "content": "Bovine parainfluenza virus type 3 (PIV-3) has a buoyant density of 1.197. The RNA of PIV-3, like that of Sendai virus, is a single continuous chain which lacks polyadenylic acid sequences and tends to self-anneal to a marked extent. It has a sedimentation coefficient of 42S and a molecular weight of 4.5 X 10(6), being slightly smaller than Sendai virus RNA (47S, 5.3 X 10(6)). PIV-3 has 5 main structural proteins, of which 2 are glycoproteins. The molecular weights of protein 1, protein 2, protein 3, glycoprotein 1, and glycoprotein 2 were estimated to be 79,000, 68,000, 35,000, 69,000, and 55,000, respectively. Protein 2 was suggested to be nucleocapsid protein.", "contents": "Characterization of bovine parainfluenza virus type 3. Bovine parainfluenza virus type 3 (PIV-3) has a buoyant density of 1.197. The RNA of PIV-3, like that of Sendai virus, is a single continuous chain which lacks polyadenylic acid sequences and tends to self-anneal to a marked extent. It has a sedimentation coefficient of 42S and a molecular weight of 4.5 X 10(6), being slightly smaller than Sendai virus RNA (47S, 5.3 X 10(6)). PIV-3 has 5 main structural proteins, of which 2 are glycoproteins. The molecular weights of protein 1, protein 2, protein 3, glycoprotein 1, and glycoprotein 2 were estimated to be 79,000, 68,000, 35,000, 69,000, and 55,000, respectively. Protein 2 was suggested to be nucleocapsid protein."}
{"id": "PMID:228164", "title": "Enrichment of C-type virus mRNA from immunochemically separated polyribosomes.", "content": "A method for the isolation of mRNA from a c-type virus-positive cell (JLS-V6) has been developed. This method consisted of (i) specific immunochemical precipitation of polyribosomes synthesizing viral proteins, (ii) extraction of the mRNA from the polyribosome/antigen/antibody complex, and (iii) separation of poly-A containing RNA by affinity chromatography on oligo-d(T)-cellulose. Three size classes of virus specific poly-A containing mRNA are identified and they are 35S, 20S-25S, and 10S-15S.", "contents": "Enrichment of C-type virus mRNA from immunochemically separated polyribosomes. A method for the isolation of mRNA from a c-type virus-positive cell (JLS-V6) has been developed. This method consisted of (i) specific immunochemical precipitation of polyribosomes synthesizing viral proteins, (ii) extraction of the mRNA from the polyribosome/antigen/antibody complex, and (iii) separation of poly-A containing RNA by affinity chromatography on oligo-d(T)-cellulose. Three size classes of virus specific poly-A containing mRNA are identified and they are 35S, 20S-25S, and 10S-15S."}
{"id": "PMID:228165", "title": "Effect of nucleosides on interferon production and development of antiviral state induced by poly I.poly C.", "content": "Effect of nucleosides both on induction of antiviral state in chick embryo cells (CEC) or rabbit kidney cells (RK13) and on interferon production in RK13 or mouse fibroblast cells (L cells) by polyriboinosinic-polyribocytidylic acid (poly I.poly C) was studied. Addition of inosine or a fifty-fifty mixture of inosine and uridine at a final concentration of 0.1 mM to 10 mM to a growth medium enhanced development of antiviral state in CEC. The nucleoside effect was also observed in RK13 at 0.1 mM but not at a concentration higher than 1 mM. Interferon production in RK13 by superinduction (sequential treatment with metabolic inhibitors after exposure to poly I.poly C) was enhanced 1.5- to 4.0-fold by addition of the nucleoside mixture to the growth medium. When RK13 was pretreated with 10 units per ml of interferon and then superinduced by inhibitors, the enhancing effect of nucleosides on interferon production was not observed. Interferon production in L cells was potentiated a little by addition of 1 mM of the nucleoside mixture to the growth medium. The effect of nucleoside was not observed when the nucleosides were added after exposure to poly I.poly C. The nucleoside effect may be applicable for production of high titered interferon.", "contents": "Effect of nucleosides on interferon production and development of antiviral state induced by poly I.poly C. Effect of nucleosides both on induction of antiviral state in chick embryo cells (CEC) or rabbit kidney cells (RK13) and on interferon production in RK13 or mouse fibroblast cells (L cells) by polyriboinosinic-polyribocytidylic acid (poly I.poly C) was studied. Addition of inosine or a fifty-fifty mixture of inosine and uridine at a final concentration of 0.1 mM to 10 mM to a growth medium enhanced development of antiviral state in CEC. The nucleoside effect was also observed in RK13 at 0.1 mM but not at a concentration higher than 1 mM. Interferon production in RK13 by superinduction (sequential treatment with metabolic inhibitors after exposure to poly I.poly C) was enhanced 1.5- to 4.0-fold by addition of the nucleoside mixture to the growth medium. When RK13 was pretreated with 10 units per ml of interferon and then superinduced by inhibitors, the enhancing effect of nucleosides on interferon production was not observed. Interferon production in L cells was potentiated a little by addition of 1 mM of the nucleoside mixture to the growth medium. The effect of nucleoside was not observed when the nucleosides were added after exposure to poly I.poly C. The nucleoside effect may be applicable for production of high titered interferon."}
{"id": "PMID:228166", "title": "Reactivity of neutralizing antibodies with different specificities to H particles of poliovirus.", "content": "In order to elucidate the antigenic structure of poliovirus, the reactivity of antibody produced with H antigenic particles of Mahoney strain (polio type 1) was investigated. Injection of H particles of Mahoney strain into rabbits yielded neutralizing antibody as well as CF-N and CF-H antibodies. This result coincided with the report by Hinuma and coworkers. Neutralization tests with inhibitor resistant Mahoney mutants revealed that the neutralizing antibody produced with H particles was of HN31 type, one of the five different kinds of polio neutralizing antibodies reported previously (14). Absorption experiments with H particles on different neutralizing antibodies and analysis of antibody eluted by acid dissociation from antiserum-treated H particles also showed that the HN31 type antibody specifically combined with H particles of Mahoney strain. Since the H particle of poliovirus is known to be deficient in VP4, these results seems to indicate that the HN31 type antibody reacts with a structural part(s) of poliovirus other than VP4.", "contents": "Reactivity of neutralizing antibodies with different specificities to H particles of poliovirus. In order to elucidate the antigenic structure of poliovirus, the reactivity of antibody produced with H antigenic particles of Mahoney strain (polio type 1) was investigated. Injection of H particles of Mahoney strain into rabbits yielded neutralizing antibody as well as CF-N and CF-H antibodies. This result coincided with the report by Hinuma and coworkers. Neutralization tests with inhibitor resistant Mahoney mutants revealed that the neutralizing antibody produced with H particles was of HN31 type, one of the five different kinds of polio neutralizing antibodies reported previously (14). Absorption experiments with H particles on different neutralizing antibodies and analysis of antibody eluted by acid dissociation from antiserum-treated H particles also showed that the HN31 type antibody specifically combined with H particles of Mahoney strain. Since the H particle of poliovirus is known to be deficient in VP4, these results seems to indicate that the HN31 type antibody reacts with a structural part(s) of poliovirus other than VP4."}
{"id": "PMID:228171", "title": "Bilateral Wilms tumor presenting with acute renal failure and clinical findings mimicking cardiac failure.", "content": "A six-year-old girl presented with clinical signs and symptoms of right-sided heart failure. Cardiac catheterization demonstrated filling defects in both pulmonary arteries felt to represent metastatic lesions or thromboemboli. Intravenous pyelogram revealed bilateral renal masses and intrarenal obstruction. Acute renal failure was unresponsive to standard therapy. An open renal biopsy revealed Wilms tumor with favorable histology. Aggressive chemotherapy and irradiation were undertaken and renal function returned. This case adds to the heterogeneity of presentations described for Wilms tumor, and review of the literature reveals no other cases with similar presenting signs.", "contents": "Bilateral Wilms tumor presenting with acute renal failure and clinical findings mimicking cardiac failure. A six-year-old girl presented with clinical signs and symptoms of right-sided heart failure. Cardiac catheterization demonstrated filling defects in both pulmonary arteries felt to represent metastatic lesions or thromboemboli. Intravenous pyelogram revealed bilateral renal masses and intrarenal obstruction. Acute renal failure was unresponsive to standard therapy. An open renal biopsy revealed Wilms tumor with favorable histology. Aggressive chemotherapy and irradiation were undertaken and renal function returned. This case adds to the heterogeneity of presentations described for Wilms tumor, and review of the literature reveals no other cases with similar presenting signs."}
{"id": "PMID:228168", "title": "[Possible pathways for acetyl-CoA formation by purple bacteria].", "content": "Purple sulfur (Ectothiorhodospira shaposhnikovii, Chromatium minutissimum, Lamprobacter modestohalophilus, Thiocapsa roseopersicina) and nonsulfur (Rhodospirillum rubrum, Rhodopseudomonas palustris, Rhodopseudomonas spheroides) bacteria are capable of forming acetyl-CoA synthetase, phosphotransacetylase and acetokinase independent of the medium composition and growth conditions. In all of the purple sulfur bacteria with an exception of E. shaposhnikovii, the activity of acetokinase is much higher than in purple nonsulfur bacteria. Apart from being involved in the synthesis of acetyl-CoA, such enzymes as phosphotransacetylase, acetokinase and adenylate kinase may play an important role in energy processes of some purple bacteria in the dark.", "contents": "[Possible pathways for acetyl-CoA formation by purple bacteria]. Purple sulfur (Ectothiorhodospira shaposhnikovii, Chromatium minutissimum, Lamprobacter modestohalophilus, Thiocapsa roseopersicina) and nonsulfur (Rhodospirillum rubrum, Rhodopseudomonas palustris, Rhodopseudomonas spheroides) bacteria are capable of forming acetyl-CoA synthetase, phosphotransacetylase and acetokinase independent of the medium composition and growth conditions. In all of the purple sulfur bacteria with an exception of E. shaposhnikovii, the activity of acetokinase is much higher than in purple nonsulfur bacteria. Apart from being involved in the synthesis of acetyl-CoA, such enzymes as phosphotransacetylase, acetokinase and adenylate kinase may play an important role in energy processes of some purple bacteria in the dark."}
{"id": "PMID:228173", "title": "Oxidative inactivation of the molybdenum-iron-protein component of nitrogenase from clostridium pasteurianum.", "content": "The sensitivity of the molybdenum-iron(MoFe)-protein of Clostridium pasteurianum nitrogenase toward oxidation has been studied by determining the enzymatic activity of this component after incubating it anaerobically in ferricyanide solutions of various oxidizing strengths (as measured by their oxidation potentials). It was found that the MoFe-protein remains active at potentials up to +350 mV (vs. standard hydrogen electrode) but becomes readily inactivated at more oxidizing potentials, after a lag period, depending on the potential level and temperature. Oxidative inactivation by ferricyanide results in the release of most of the Mo, Fe and S atoms from the protein which causes the loss of the absorption bands in the visible region. The metals and sulfur could be re-incorporated by incubation in a mixture containing thiol, sulfide, molybdate, and ferric iron. The EPR spectrum of the oxidatively inactivated MoFe-protein showed that both the high- and low-field signals are readily affected. Re-incorporation of the metals and sulfur into the \"bleached\" protein produced an EPR spectrum similar to that of the air-inactivated protein. Incubation of the Mo-Fe-protein with mersalyl abolished its enzymic activity. The difference spectrum before and after mersalyl treatment resembles that of the soluble spinach ferredoxin.", "contents": "Oxidative inactivation of the molybdenum-iron-protein component of nitrogenase from clostridium pasteurianum. The sensitivity of the molybdenum-iron(MoFe)-protein of Clostridium pasteurianum nitrogenase toward oxidation has been studied by determining the enzymatic activity of this component after incubating it anaerobically in ferricyanide solutions of various oxidizing strengths (as measured by their oxidation potentials). It was found that the MoFe-protein remains active at potentials up to +350 mV (vs. standard hydrogen electrode) but becomes readily inactivated at more oxidizing potentials, after a lag period, depending on the potential level and temperature. Oxidative inactivation by ferricyanide results in the release of most of the Mo, Fe and S atoms from the protein which causes the loss of the absorption bands in the visible region. The metals and sulfur could be re-incorporated by incubation in a mixture containing thiol, sulfide, molybdate, and ferric iron. The EPR spectrum of the oxidatively inactivated MoFe-protein showed that both the high- and low-field signals are readily affected. Re-incorporation of the metals and sulfur into the \"bleached\" protein produced an EPR spectrum similar to that of the air-inactivated protein. Incubation of the Mo-Fe-protein with mersalyl abolished its enzymic activity. The difference spectrum before and after mersalyl treatment resembles that of the soluble spinach ferredoxin."}
{"id": "PMID:228174", "title": "Properties of protease-treated cytochrome c oxidase from beef heart.", "content": "About 45% of the protein can be removed from oxidized cytochrome c oxidase by treatment with proteolytic enzymes under a variety of conditions, leading to an increased heme to protein ratio. The principal spectroscopic parameters of cytochrome c oxidase are retained in the protease-treated enzyme. Of the overall catalytic activity 20% remained after digestion; the electron-transfer reactions were impaired but the affinity for cytochrome c appeared unchanged. Proteolysis resulted in removal of the hydrophobic subunit III and most of the smaller hydrophilic subunits, leaving a core, which basically consists of the two largest subunits I and II. The subunits I and/or II carry the prosthetic groups of the enzyme and at least one of the cytochrome c binding sites. The smaller subunits, however, are essential for optimal electron transfer and possibly have other functions as well.", "contents": "Properties of protease-treated cytochrome c oxidase from beef heart. About 45% of the protein can be removed from oxidized cytochrome c oxidase by treatment with proteolytic enzymes under a variety of conditions, leading to an increased heme to protein ratio. The principal spectroscopic parameters of cytochrome c oxidase are retained in the protease-treated enzyme. Of the overall catalytic activity 20% remained after digestion; the electron-transfer reactions were impaired but the affinity for cytochrome c appeared unchanged. Proteolysis resulted in removal of the hydrophobic subunit III and most of the smaller hydrophilic subunits, leaving a core, which basically consists of the two largest subunits I and II. The subunits I and/or II carry the prosthetic groups of the enzyme and at least one of the cytochrome c binding sites. The smaller subunits, however, are essential for optimal electron transfer and possibly have other functions as well."}
{"id": "PMID:228175", "title": "The time course of the phosphorylation of proteins in the synaptic plasma membrane and the effect of certain cations.", "content": "The phosphorylation of proteins in the synaptic plasma membrane is a rather slow reaction taking several minutes to saturate all the phosphate acceptor sites. (The time for half the protein bound phosphate groups to turnover is about 1 min). A divalent cation is needed as a cofactor for the reaction. At high (0.5 mM) ATP concentrations Mg2+ is more effective than Mn2+ but at low (10 microM) ATP concentrations the reverse is the case. Zn2+ and Ca2+ support very little phosphorylation.", "contents": "The time course of the phosphorylation of proteins in the synaptic plasma membrane and the effect of certain cations. The phosphorylation of proteins in the synaptic plasma membrane is a rather slow reaction taking several minutes to saturate all the phosphate acceptor sites. (The time for half the protein bound phosphate groups to turnover is about 1 min). A divalent cation is needed as a cofactor for the reaction. At high (0.5 mM) ATP concentrations Mg2+ is more effective than Mn2+ but at low (10 microM) ATP concentrations the reverse is the case. Zn2+ and Ca2+ support very little phosphorylation."}
{"id": "PMID:228176", "title": "Characterisation of poly(ADP-Rib) polymerase activity in nuclei from the slime mould Dictyostelium discoideum.", "content": "Nuclei isolated from D. discoideum and incubated in vitro with 3H-NAD synthesise poly(ADP-Rib). The optimum incubation conditions for the poly(ADP-Rib) polymerase were determined. The Km of the enzyme is 18 microM NAD and it is inhibited by nicotinamide. Most of the poly(ADP-Rib) synthesised is attached to nuclear proteins.", "contents": "Characterisation of poly(ADP-Rib) polymerase activity in nuclei from the slime mould Dictyostelium discoideum. Nuclei isolated from D. discoideum and incubated in vitro with 3H-NAD synthesise poly(ADP-Rib). The optimum incubation conditions for the poly(ADP-Rib) polymerase were determined. The Km of the enzyme is 18 microM NAD and it is inhibited by nicotinamide. Most of the poly(ADP-Rib) synthesised is attached to nuclear proteins."}
{"id": "PMID:228178", "title": "[DNA fragmentation of chicken adenovirus CELO by specific endonucleases R. HpaI, R. EcoRI, R. HindIII].", "content": "The effect of specific endonucleases on DNA chiken adenovirus CELO was studed. It was shown that endonucleases R. HpaI, R. EcoRI and R. HindIII cleaved viral DNA into 5,7 and 9 specific fragments, respectively. The sequence of fragments (physical map) was determined and found to be: D-A-E-C-B for enzyme R. HpaI; B-(EG)-C-A-D-F for enzyme R. EcoRI; H-F-A-C-G-B-D-E-I for enzyme R. HindIII.", "contents": "[DNA fragmentation of chicken adenovirus CELO by specific endonucleases R. HpaI, R. EcoRI, R. HindIII]. The effect of specific endonucleases on DNA chiken adenovirus CELO was studed. It was shown that endonucleases R. HpaI, R. EcoRI and R. HindIII cleaved viral DNA into 5,7 and 9 specific fragments, respectively. The sequence of fragments (physical map) was determined and found to be: D-A-E-C-B for enzyme R. HpaI; B-(EG)-C-A-D-F for enzyme R. EcoRI; H-F-A-C-G-B-D-E-I for enzyme R. HindIII."}
{"id": "PMID:228180", "title": "[Electron paramagnetic resonance study of electron transport in photosynthetic systems. VIII. The interplay between two photosystems and kinetics of P700 redox transients under various conditions of flash excitation].", "content": "The kinetics P700 redox transients in bean chloroplasts induced by short (t 1/2 = 7 microsecond) flashes of white light has been studied. The flashes were fired in the dark or simultaneously with the continuous background far red light (707 nm). After oxidation of electron transport chain by 707 nm light only 50% of P700+ centres were reduced by photosystem 2 in response to the first flash of saturating intensity. The total reduction of P700+ centres was observed only after two or more saturating flashes. The similar data were obtained for various native photosynthetic systems (bean leaves and leaves of other higher plants). It has been shown that the quantitative difference in P700 behaviour after the first and following flashes may be interpreted in terms of a mechanism of the plastoquinol oxidation by photosystem 1. Twofold oxidation of one molecule of plastoquinol was assumed as its successive oxidation to plastosemiquinone and plastoquinone by different acceptors localized nea the same P700 centre (cytochrome f and plastocyanine). It has been shown that one molecule of plastoquinol was arised due to the interaction of two plastosemiquinones reduced by different P680 centre.", "contents": "[Electron paramagnetic resonance study of electron transport in photosynthetic systems. VIII. The interplay between two photosystems and kinetics of P700 redox transients under various conditions of flash excitation]. The kinetics P700 redox transients in bean chloroplasts induced by short (t 1/2 = 7 microsecond) flashes of white light has been studied. The flashes were fired in the dark or simultaneously with the continuous background far red light (707 nm). After oxidation of electron transport chain by 707 nm light only 50% of P700+ centres were reduced by photosystem 2 in response to the first flash of saturating intensity. The total reduction of P700+ centres was observed only after two or more saturating flashes. The similar data were obtained for various native photosynthetic systems (bean leaves and leaves of other higher plants). It has been shown that the quantitative difference in P700 behaviour after the first and following flashes may be interpreted in terms of a mechanism of the plastoquinol oxidation by photosystem 1. Twofold oxidation of one molecule of plastoquinol was assumed as its successive oxidation to plastosemiquinone and plastoquinone by different acceptors localized nea the same P700 centre (cytochrome f and plastocyanine). It has been shown that one molecule of plastoquinol was arised due to the interaction of two plastosemiquinones reduced by different P680 centre."}
{"id": "PMID:228186", "title": "Survival and herpes virus production of normal and xeroderma pigmentosum fibroblasts after treatment with formaldehyde.", "content": "The survival of excision-deficient and of excision-proficient (variant) skin fibroblasts from xeroderma pigmentosum (XP) donors was about 5 times and twice, respectively, more sensitive to formaldehyde (FA) treatment than that of skin fibroblasts from healthy and XP heterozygote donors. The capacity of FA-treated host cells to further support Herpes virus (HSV) replication was also more sensitive to FA in XP12BE (group A) than in normal (KD) cells. An important recovery of this capacity occurred in both cell types when they were infected at increasing times (up to 36 h) after FA treatment. This contrasts with the decreasing capacity observed in XP12BE when similarly infected at increasing times after exposure to ultraviolet. In addition, the survival of FA-treated HSV was comparable in KD and XP12BE cells, whereas that of UV-irradiated HSV was much lower in XP12BE than in KD cells.", "contents": "Survival and herpes virus production of normal and xeroderma pigmentosum fibroblasts after treatment with formaldehyde. The survival of excision-deficient and of excision-proficient (variant) skin fibroblasts from xeroderma pigmentosum (XP) donors was about 5 times and twice, respectively, more sensitive to formaldehyde (FA) treatment than that of skin fibroblasts from healthy and XP heterozygote donors. The capacity of FA-treated host cells to further support Herpes virus (HSV) replication was also more sensitive to FA in XP12BE (group A) than in normal (KD) cells. An important recovery of this capacity occurred in both cell types when they were infected at increasing times (up to 36 h) after FA treatment. This contrasts with the decreasing capacity observed in XP12BE when similarly infected at increasing times after exposure to ultraviolet. In addition, the survival of FA-treated HSV was comparable in KD and XP12BE cells, whereas that of UV-irradiated HSV was much lower in XP12BE than in KD cells."}
{"id": "PMID:228179", "title": "[Myxovirus structural investigations by spin probe methods. II. Influence of rimantadine on the structure of viral and artificial lipid membranes].", "content": "The lipid membrane structure of two myxoviruses (influenza and Sendai viruses), red blood cells and liposomes (prepared from total lipids of Sendai virus) have been investigated in the presence of rimantadine by means of two spin probes C5 and C6--the iminoxyl derivatives of stearic acids. Rimantadine was shown to penetrate the lipid membranes of myxoviruses and red blood sells and change the structure of the lipid phase no less than 0.8 nm apart from the viral surface. In the depth of 2.2 nm the structure of these lipid membranes remains unchanged after addition of rimantadine. Rimantadine also displaces the phase transition points of cell and viral lipid membranes to lower temperatures. Rimantadine does not change the lipid bilayer structure of liposomes 0.8 nm apart from its surface. These finding allow to suggest that rimantadine affects the cell and viral lipoprotein membranes.", "contents": "[Myxovirus structural investigations by spin probe methods. II. Influence of rimantadine on the structure of viral and artificial lipid membranes]. The lipid membrane structure of two myxoviruses (influenza and Sendai viruses), red blood cells and liposomes (prepared from total lipids of Sendai virus) have been investigated in the presence of rimantadine by means of two spin probes C5 and C6--the iminoxyl derivatives of stearic acids. Rimantadine was shown to penetrate the lipid membranes of myxoviruses and red blood sells and change the structure of the lipid phase no less than 0.8 nm apart from the viral surface. In the depth of 2.2 nm the structure of these lipid membranes remains unchanged after addition of rimantadine. Rimantadine also displaces the phase transition points of cell and viral lipid membranes to lower temperatures. Rimantadine does not change the lipid bilayer structure of liposomes 0.8 nm apart from its surface. These finding allow to suggest that rimantadine affects the cell and viral lipoprotein membranes."}
{"id": "PMID:228189", "title": "Polyaxonal myelination in developing dystrophic and normal mouse nerves.", "content": "Myelin-forming Schwann cells in the peripheral nervous system characteristically surround and myelinate only single axons. Polyaxonal myelination is an anomaly of this one-to-one relationship whereby one normal-appearing Schwann cell myelinates multiple axons. We examined the ventral roots and the proximal sciatic and posterior tibial nerves of developing normal mice and of dy2J/dy2J dystrophic mice with proximal failure of myelination. Polyaxonal myelination was a rare feature in normal nerves. Examples of polyaxonal myelination were observed six times more often in dystrophic than in normal mice and were most abundant in proximal sciatic nerves. Polyaxonal myelination could result from either an axonal or a Schwann-cell abnormality, or it may be the nonspecific response of uncommitted Schwann cells to an early failure of myelination.", "contents": "Polyaxonal myelination in developing dystrophic and normal mouse nerves. Myelin-forming Schwann cells in the peripheral nervous system characteristically surround and myelinate only single axons. Polyaxonal myelination is an anomaly of this one-to-one relationship whereby one normal-appearing Schwann cell myelinates multiple axons. We examined the ventral roots and the proximal sciatic and posterior tibial nerves of developing normal mice and of dy2J/dy2J dystrophic mice with proximal failure of myelination. Polyaxonal myelination was a rare feature in normal nerves. Examples of polyaxonal myelination were observed six times more often in dystrophic than in normal mice and were most abundant in proximal sciatic nerves. Polyaxonal myelination could result from either an axonal or a Schwann-cell abnormality, or it may be the nonspecific response of uncommitted Schwann cells to an early failure of myelination."}
{"id": "PMID:228187", "title": "Effects of D-penicillamine on neuromuscular transmission in rats.", "content": "Treatment of patients with D-penicillamine (D-P) has been associated with a syndrome similar to myasthenia gravis (MG). To explore this association, we examined the effects of D-P on neuromuscular transmission in rat muscle. In the first experiment, bath-applied D-P had no significant effect on either miniature endplate potential (MEPP) amplitude or action potential (AP) amplitude. Endplate potential (EPP) amplitude and spontaneous MEPP frequency decreased significantly at concentrations approximately 40 times the maximum human therapeutic level. In the second experiment, rats receiving D-P by daily injections for 33 to 37 days did not differ from controls in any of the measured electrophysiologic characteristics. Electron microscopy of muscle endplates from rats treated with D-P showed no evidence of degeneration or simplification. In all cases, thymus histology by light microscopy was normal, and no antireceptor antibodies were found. Thus, D-P has a mild direct presynaptic effect on neuromuscular transmission at high concentrations, but this effect is too small to account for the weakness seen in the myasthenia-like syndrome in humans.", "contents": "Effects of D-penicillamine on neuromuscular transmission in rats. Treatment of patients with D-penicillamine (D-P) has been associated with a syndrome similar to myasthenia gravis (MG). To explore this association, we examined the effects of D-P on neuromuscular transmission in rat muscle. In the first experiment, bath-applied D-P had no significant effect on either miniature endplate potential (MEPP) amplitude or action potential (AP) amplitude. Endplate potential (EPP) amplitude and spontaneous MEPP frequency decreased significantly at concentrations approximately 40 times the maximum human therapeutic level. In the second experiment, rats receiving D-P by daily injections for 33 to 37 days did not differ from controls in any of the measured electrophysiologic characteristics. Electron microscopy of muscle endplates from rats treated with D-P showed no evidence of degeneration or simplification. In all cases, thymus histology by light microscopy was normal, and no antireceptor antibodies were found. Thus, D-P has a mild direct presynaptic effect on neuromuscular transmission at high concentrations, but this effect is too small to account for the weakness seen in the myasthenia-like syndrome in humans."}
{"id": "PMID:228188", "title": "Penicillamine-induced myasthenic responses in the guinea pig.", "content": "To study the basis for the myasthenic illness that develops in some patients receiving D-penicillamine (D-P), we measured neuromuscular transmission in D-P-treated guinea pigs. Treated animals manifested edrophonium chloride-repairable decremental responses to 30-Hz nerve stimulation (8.5% +/- 1.5%--mean +/- SEM; N = 16) compared with the response in saline-treated control animals (-0.3% +/- 0.85%, N = 10, p less than 0.005). Posttetanic phenomena were studied in 5 treated animals; 3 revealed posttetanic exhaustion. Miniature endplate potential (MEPP) amplitudes were significantly reduced in 11 treated animals (0.612 +/- 0.016 mV) compared with 6 controls (0.713 +/- 0.024 mV, p less than 0.01). The MEPP frequency appeared reduced in treated animals. Both MEPP amplitude and MEEP frequency correlated with the decrement.", "contents": "Penicillamine-induced myasthenic responses in the guinea pig. To study the basis for the myasthenic illness that develops in some patients receiving D-penicillamine (D-P), we measured neuromuscular transmission in D-P-treated guinea pigs. Treated animals manifested edrophonium chloride-repairable decremental responses to 30-Hz nerve stimulation (8.5% +/- 1.5%--mean +/- SEM; N = 16) compared with the response in saline-treated control animals (-0.3% +/- 0.85%, N = 10, p less than 0.005). Posttetanic phenomena were studied in 5 treated animals; 3 revealed posttetanic exhaustion. Miniature endplate potential (MEPP) amplitudes were significantly reduced in 11 treated animals (0.612 +/- 0.016 mV) compared with 6 controls (0.713 +/- 0.024 mV, p less than 0.01). The MEPP frequency appeared reduced in treated animals. Both MEPP amplitude and MEEP frequency correlated with the decrement."}
{"id": "PMID:228196", "title": "Onset of neural function in the lateral line.", "content": "The development of the nervous system includes the formation of specific neuronal connections. Some insight into the mechanisms by which these connections are made may be obtained by determining the order in which the elements of a developing system begin to function and examining any changes that may occur in the system shortly after it begins functioning. I have investigated the lateral line of the South African clawed frog, Xenopus laevis and I have classified the afferent system into three elements. First, the transduction mechanism, which includes all components that couple the water vibrations to the release of transmitter from the hair cell. Second, the afferent synapse, at which there is transmitter release and subsequent postsynaptic conductance changes. And third, the afferent axon. I report here experiments suggesting that these elements become functional in the following order: first, the axon can conduct action potentials; second, transmission is established; third, the transduction mechanism can modulate transmitter release. This same sequence has been reported in a system related to the lateral line, the auditory pathway of mammals.", "contents": "Onset of neural function in the lateral line. The development of the nervous system includes the formation of specific neuronal connections. Some insight into the mechanisms by which these connections are made may be obtained by determining the order in which the elements of a developing system begin to function and examining any changes that may occur in the system shortly after it begins functioning. I have investigated the lateral line of the South African clawed frog, Xenopus laevis and I have classified the afferent system into three elements. First, the transduction mechanism, which includes all components that couple the water vibrations to the release of transmitter from the hair cell. Second, the afferent synapse, at which there is transmitter release and subsequent postsynaptic conductance changes. And third, the afferent axon. I report here experiments suggesting that these elements become functional in the following order: first, the axon can conduct action potentials; second, transmission is established; third, the transduction mechanism can modulate transmitter release. This same sequence has been reported in a system related to the lateral line, the auditory pathway of mammals."}
{"id": "PMID:228197", "title": "Gonadotropin-releasing hormone analogue binds to luteal cells and inhibits progesterone production.", "content": "Although gonadotropin-releasing hormone (GnRH) is believed to mediate the hypothalamic control of pituitary gonadotropin secretion, continuous or repeated administration of GnRH or its agonist analogues has been shown to cause paradoxical antifertility effects in several species, including primates. GnRH-induced interruption of reproductive cycles and pregnancy is associated with diminished progesterone production, implying defective function of the corpus luteum. These luteolytic effects have been attributed to the well recognized desensitising actions of elevated luteinising hormone (LH) levels on ovarian LH receptors and steroidogenesis, subsequent to GnRH-induced gonadotropin release from the anterior pituitary. However, treatment with high doses of exogenous LH did not cause suppression of serum progesterone levels during early pregnancy in rats, whereas a highly active GnRH analogue was effective in this regard. These observations suggested that GnRH and its agonist analogues, given in high or sustained doses, can exert a direct action on the ovary that is independent of the pituitary. This hypothesis was further supported by the ability of GnRH and its agonists to inhibit human chorionic gonadotropin (HCG)-induced ovarian and uterine weight gain in hypophysectomised rats and to delay the onset of puberty in intact female rats. Also, GnRH and its agonist analogues have recently been shown to inhibit steroidogenesis induced by follicle-stimulating hormone (FSH) in cultured granulosa cells, confirming the direct action of such peptides on the ovarian follicle. The marked inhibitory effects of GnRH and its agonists on corpus luteum function suggest that these compounds could exert direct actions by binding to specific receptors on luteal cells. The present experiments, which examine the effects of GnRH agonists on luteal steroidogenesis, demonstrate the existence of such actions and their mediation by specific high-affinity receptor sites present in luteal cell membranes.", "contents": "Gonadotropin-releasing hormone analogue binds to luteal cells and inhibits progesterone production. Although gonadotropin-releasing hormone (GnRH) is believed to mediate the hypothalamic control of pituitary gonadotropin secretion, continuous or repeated administration of GnRH or its agonist analogues has been shown to cause paradoxical antifertility effects in several species, including primates. GnRH-induced interruption of reproductive cycles and pregnancy is associated with diminished progesterone production, implying defective function of the corpus luteum. These luteolytic effects have been attributed to the well recognized desensitising actions of elevated luteinising hormone (LH) levels on ovarian LH receptors and steroidogenesis, subsequent to GnRH-induced gonadotropin release from the anterior pituitary. However, treatment with high doses of exogenous LH did not cause suppression of serum progesterone levels during early pregnancy in rats, whereas a highly active GnRH analogue was effective in this regard. These observations suggested that GnRH and its agonist analogues, given in high or sustained doses, can exert a direct action on the ovary that is independent of the pituitary. This hypothesis was further supported by the ability of GnRH and its agonists to inhibit human chorionic gonadotropin (HCG)-induced ovarian and uterine weight gain in hypophysectomised rats and to delay the onset of puberty in intact female rats. Also, GnRH and its agonist analogues have recently been shown to inhibit steroidogenesis induced by follicle-stimulating hormone (FSH) in cultured granulosa cells, confirming the direct action of such peptides on the ovarian follicle. The marked inhibitory effects of GnRH and its agonists on corpus luteum function suggest that these compounds could exert direct actions by binding to specific receptors on luteal cells. The present experiments, which examine the effects of GnRH agonists on luteal steroidogenesis, demonstrate the existence of such actions and their mediation by specific high-affinity receptor sites present in luteal cell membranes."}
{"id": "PMID:228198", "title": "Phosphorylation of adenosine in aqueous solution by electric discharges.", "content": "Dehydration reactions involving condensing reagents in aqueous solution have been studied as models of chemical evolution, and one such reagent has been found to be produced in the supposed primitive Earth conditions. We assumed that the dehydration condensation in aqueous solution could occur if the condensing reagents, which appear to be produced by electric discharges in the gas phase, could be carried to the aqueous solution through the recycling of water washing the wall of the vessel. We present here an experimental study of the dehydration condensation between phosphate and adenosine in aqueous solution using a new discharge apparatus (Fig. 1) which simulates prebiotic chemical evolution. The apparatus was designed so that water recycles in a vessel containing a solution at a relatively low temperature (approximately 30 degrees C), achieved by showering water at 18 degrees C from above the vessel. This is a simulation of the recycling system of water on the Earth, depending on a large difference in temperature between the ocean surface and the sky.", "contents": "Phosphorylation of adenosine in aqueous solution by electric discharges. Dehydration reactions involving condensing reagents in aqueous solution have been studied as models of chemical evolution, and one such reagent has been found to be produced in the supposed primitive Earth conditions. We assumed that the dehydration condensation in aqueous solution could occur if the condensing reagents, which appear to be produced by electric discharges in the gas phase, could be carried to the aqueous solution through the recycling of water washing the wall of the vessel. We present here an experimental study of the dehydration condensation between phosphate and adenosine in aqueous solution using a new discharge apparatus (Fig. 1) which simulates prebiotic chemical evolution. The apparatus was designed so that water recycles in a vessel containing a solution at a relatively low temperature (approximately 30 degrees C), achieved by showering water at 18 degrees C from above the vessel. This is a simulation of the recycling system of water on the Earth, depending on a large difference in temperature between the ocean surface and the sky."}
{"id": "PMID:228201", "title": "Endogenous viral genes are non-essential in the chicken.", "content": "DNA sequences homologous to the genomes of type C retroviruses are widespread among vertebrates. Ten genetic loci containing endogenous viral DNA sequences have been documented in the white Leghorn chicken alone. Six of these genetic loci are associated with the production of virus or of viral proteins in embryonic fibroblasts (refs 2--4, and S.M.A., L, B. Crittenden and E.G.B., in preparation) and one of the loci may be expressed in the erythroblasts of 5-day-old embryos. The abiquitous presence of endogenous viral genes among vertebrate species and the association of their expression with development of the haematopoietic system in the mouse have led to the proposal that these genes are involved in ontogeny. In addition, the genes may be implicated in oncogenesis as in the case of the AKR mouse in which a high incidence of spontaneous leukaemia is associated with the expression of endogenous murine laukaemia virus genomes. We report here the production of a fertile rooster which lacks avian leukosis virus-related endogenous viral genes and which seems to be completely normal and healthy. Thus, endogenous viral genes are apparently not essential for the normal development of the chicken. An endogenous virus-free state has also been reported for three species of jungle fowl and for the B-type viral genes of the mouse.", "contents": "Endogenous viral genes are non-essential in the chicken. DNA sequences homologous to the genomes of type C retroviruses are widespread among vertebrates. Ten genetic loci containing endogenous viral DNA sequences have been documented in the white Leghorn chicken alone. Six of these genetic loci are associated with the production of virus or of viral proteins in embryonic fibroblasts (refs 2--4, and S.M.A., L, B. Crittenden and E.G.B., in preparation) and one of the loci may be expressed in the erythroblasts of 5-day-old embryos. The abiquitous presence of endogenous viral genes among vertebrate species and the association of their expression with development of the haematopoietic system in the mouse have led to the proposal that these genes are involved in ontogeny. In addition, the genes may be implicated in oncogenesis as in the case of the AKR mouse in which a high incidence of spontaneous leukaemia is associated with the expression of endogenous murine laukaemia virus genomes. We report here the production of a fertile rooster which lacks avian leukosis virus-related endogenous viral genes and which seems to be completely normal and healthy. Thus, endogenous viral genes are apparently not essential for the normal development of the chicken. An endogenous virus-free state has also been reported for three species of jungle fowl and for the B-type viral genes of the mouse."}
{"id": "PMID:228202", "title": "A novel analgesic dipeptide from bovine brain is a possible Met-enkephalin releaser.", "content": "It is generally accepted that morphine exerts its analgesic effect by binding to specific opiate receptors in the brain and spinal cord. Since Hughes et al. isolated and identified two endogenous pentapeptides, Met- and Leu-enkephalin, from the brain and found that they acted as agonists at opiate receptors, alpha-, beta- and gamma-endorphins, larger peptides than enkephalins and having morphine-like activity, have been identified in either the brain or pituitary of various species. Several studies have demonstrated that enkephalins possess analgesic properties and that they are distributed in the pain-mediated pathways in the central nervous system. These findings suggest that enkephalins are important neurotransmitters or neuromodulators regulating pain transmission. We now report the isolation of a novel substance which has a Met-enkephalin releasing action. Our findings suggest the possibility of a regulating mechanism for the release of endogenous opioid peptides, especially Met-enkephalin.", "contents": "A novel analgesic dipeptide from bovine brain is a possible Met-enkephalin releaser. It is generally accepted that morphine exerts its analgesic effect by binding to specific opiate receptors in the brain and spinal cord. Since Hughes et al. isolated and identified two endogenous pentapeptides, Met- and Leu-enkephalin, from the brain and found that they acted as agonists at opiate receptors, alpha-, beta- and gamma-endorphins, larger peptides than enkephalins and having morphine-like activity, have been identified in either the brain or pituitary of various species. Several studies have demonstrated that enkephalins possess analgesic properties and that they are distributed in the pain-mediated pathways in the central nervous system. These findings suggest that enkephalins are important neurotransmitters or neuromodulators regulating pain transmission. We now report the isolation of a novel substance which has a Met-enkephalin releasing action. Our findings suggest the possibility of a regulating mechanism for the release of endogenous opioid peptides, especially Met-enkephalin."}
{"id": "PMID:228203", "title": "Apamin blocks certain neurotransmitter-induced increases in potassium permeability.", "content": "Apamin is a neurotoxic polypeptide of known structure isolated from bee venom. Shuba and coworkers have recently shown that it abolishes the hyperpolarising action of externally-applied ATP on visceral smooth muscle (guinea pig stomach and taenia coli) as well as the hyperpolarisation (inhibitory junction potential) that follows stimulation of the non-adrenergic inhibitory nerve supply to these tissues.  As it has been proposed that ATP is the neurotransmitter involved in the latter response, Vladimirova and Shuba tentatively concluded that apamin is a specific postsynaptic blocking agent of this non-adrenergic, possibly 'purinergic', inhibition. We have confirmed the important observation that nanomolar concentrations of apamin reduce inhibition by ATP and by non-adrenergic nerve stimulation, but further experiments suggest that, rather than acting as a specific blocker of ATP receptors, apamin inhibits the increase in potassium permeability caused by a number of agents, including ATP.", "contents": "Apamin blocks certain neurotransmitter-induced increases in potassium permeability. Apamin is a neurotoxic polypeptide of known structure isolated from bee venom. Shuba and coworkers have recently shown that it abolishes the hyperpolarising action of externally-applied ATP on visceral smooth muscle (guinea pig stomach and taenia coli) as well as the hyperpolarisation (inhibitory junction potential) that follows stimulation of the non-adrenergic inhibitory nerve supply to these tissues.  As it has been proposed that ATP is the neurotransmitter involved in the latter response, Vladimirova and Shuba tentatively concluded that apamin is a specific postsynaptic blocking agent of this non-adrenergic, possibly 'purinergic', inhibition. We have confirmed the important observation that nanomolar concentrations of apamin reduce inhibition by ATP and by non-adrenergic nerve stimulation, but further experiments suggest that, rather than acting as a specific blocker of ATP receptors, apamin inhibits the increase in potassium permeability caused by a number of agents, including ATP."}
{"id": "PMID:228204", "title": "Desensitisation of cultured glial cells to epidermal growth factor by receptor down-regulation.", "content": "Epidermal growth factor (EGF), which can be purified from the mouse submaxillary gland or from pregnant human urine, is a potent multiplication-stimulating factor for several types of cultured cells, including human fibroblasts and glial cells. The molecule binds with high affinity and saturation kinetics to a cell-surface receptor, is subsequently internalised and finally degraded. The binding event is accompanied by a reduction in the number of EGF receptors. This phenomenon--'receptor down-regulation'--has been demonstrated with several hormones and may be a general principle for the modulation of binding groups on the outer cell surface. Further, it has been proposed that receptor loss acts to regulate the cellular response to the binding ligand. The present study provides direct experimental support for this hypothesis. It demonstrates that down-regulation of EGF receptors on glial cells causes desensitisation of the mitogenic response of these cells to subsequent stimulation with EGF.", "contents": "Desensitisation of cultured glial cells to epidermal growth factor by receptor down-regulation. Epidermal growth factor (EGF), which can be purified from the mouse submaxillary gland or from pregnant human urine, is a potent multiplication-stimulating factor for several types of cultured cells, including human fibroblasts and glial cells. The molecule binds with high affinity and saturation kinetics to a cell-surface receptor, is subsequently internalised and finally degraded. The binding event is accompanied by a reduction in the number of EGF receptors. This phenomenon--'receptor down-regulation'--has been demonstrated with several hormones and may be a general principle for the modulation of binding groups on the outer cell surface. Further, it has been proposed that receptor loss acts to regulate the cellular response to the binding ligand. The present study provides direct experimental support for this hypothesis. It demonstrates that down-regulation of EGF receptors on glial cells causes desensitisation of the mitogenic response of these cells to subsequent stimulation with EGF."}
{"id": "PMID:228205", "title": "Enkephalins presynaptically inhibit cholinergic transmission in sympathetic ganglia.", "content": "Recent biochemical and immunohistochemical studies have shown that the opioid peptides, enkephalins, occur in nerve terminals and cell bodies in mammalian sympathetic ganglia1-3. Opiates and enkephalins are thought to inhibit synaptic transmission in the peripheral nervous tissues as well as in the central nervous system4-12. The mechanisms of the opiate actions, however, are not entirely clear; both pre- and postsynaptic sites of action have been proposed7-9,11,12. As acetylcholine is known to be the major neurotransmitter in the autonomic ganglia and as the mechanism of synaptic transmission is well clarified13, analysis of the peptide action could be more easily but equally usefully carried out in the peripheral synapses than in central synapses. We now report that enkephalins presynaptically inhibit cholinergic transmission in sympathetic ganglia.", "contents": "Enkephalins presynaptically inhibit cholinergic transmission in sympathetic ganglia. Recent biochemical and immunohistochemical studies have shown that the opioid peptides, enkephalins, occur in nerve terminals and cell bodies in mammalian sympathetic ganglia1-3. Opiates and enkephalins are thought to inhibit synaptic transmission in the peripheral nervous tissues as well as in the central nervous system4-12. The mechanisms of the opiate actions, however, are not entirely clear; both pre- and postsynaptic sites of action have been proposed7-9,11,12. As acetylcholine is known to be the major neurotransmitter in the autonomic ganglia and as the mechanism of synaptic transmission is well clarified13, analysis of the peptide action could be more easily but equally usefully carried out in the peripheral synapses than in central synapses. We now report that enkephalins presynaptically inhibit cholinergic transmission in sympathetic ganglia."}
{"id": "PMID:228209", "title": "The influence of 8-Br 3', 5'-cyclic nucleotide analogs and of inhibitors of 3', 5'-cyclic nucleotide phosphodiesterase, on noradrenaline secretion and neuromuscular transmission in guinea-pig vas deferens.", "content": "The effects of 3', 5'-cyclic nucleotide phosphodiesterase (PDE) inhibitors and of 8-Br 3', 5'-cyclic nucleotide analogs on nerve-muscle transmission were studied in the guinea-pig vas deferens preincubated with 3H-noradrenaline. 8-Br cyclic AMP and the PDE inhibitors 3-isobutyl-1-methylxanthine (IBMX) and 3-propionyl-4-hydrazinopyrazolopyridine (SQ 20006) enhanced the secretion of 3H-NA evoked by transmural nerve stimulation. 8-Br cyclic GMP was without effect in this respect. The muscle contraction evoked by transmural nerve stimulation, high potassium or by application of exogenous noradrenaline was depressed by IBMX and SQ 2006. The contraction evoked by transmural nerve stimulation was enhanced by 8-Br cyclic AMP and depressed by 8-Br cyclic GMP. These findings suggest differential involvement of 3', 5'-adenosine- and guanosine-cyclic nucleotides in excitation-secretion-coupling in the noradrenergic sympathetic nerves, and in excitation-contraction-coupling in the smooth muscle, of guinea-pig vas deferens.", "contents": "The influence of 8-Br 3', 5'-cyclic nucleotide analogs and of inhibitors of 3', 5'-cyclic nucleotide phosphodiesterase, on noradrenaline secretion and neuromuscular transmission in guinea-pig vas deferens. The effects of 3', 5'-cyclic nucleotide phosphodiesterase (PDE) inhibitors and of 8-Br 3', 5'-cyclic nucleotide analogs on nerve-muscle transmission were studied in the guinea-pig vas deferens preincubated with 3H-noradrenaline. 8-Br cyclic AMP and the PDE inhibitors 3-isobutyl-1-methylxanthine (IBMX) and 3-propionyl-4-hydrazinopyrazolopyridine (SQ 20006) enhanced the secretion of 3H-NA evoked by transmural nerve stimulation. 8-Br cyclic GMP was without effect in this respect. The muscle contraction evoked by transmural nerve stimulation, high potassium or by application of exogenous noradrenaline was depressed by IBMX and SQ 2006. The contraction evoked by transmural nerve stimulation was enhanced by 8-Br cyclic AMP and depressed by 8-Br cyclic GMP. These findings suggest differential involvement of 3', 5'-adenosine- and guanosine-cyclic nucleotides in excitation-secretion-coupling in the noradrenergic sympathetic nerves, and in excitation-contraction-coupling in the smooth muscle, of guinea-pig vas deferens."}
{"id": "PMID:228210", "title": "Effects of sympathectomy on the in vivo alpha and beta-responses of the parotid gland.", "content": "Salivary secretion in response to noradrenaline and isoprenaline was measured in innervated and chronically sympathectomized parotid glands of the rat. In innervated glands, the responses to isoprenaline lasted longer than those to noradrenaline. Chronic sympathetic denervation enhanced the responses to both noradrenaline and isoprenaline. The magnitude of the supersensitivity to isoprenaline was related to the dose and the time at which the responses were analyzed. Supersensitivity was greater for the initial than for the total secretion elicited by isoprenaline. Propranolol (1 mg/kg) and phentolamine (5 mg/kg) were used in order to determine the relative participation of alpha and beta-adrenoceptors in the enhanced responses to isoprenaline. The results suggest that postjunctional supersensitivity for the secretory responses of this organ to isoprenaline is mainly mediated through beta-adrenoceptors of the secretory cells and alpha-adrenoceptors of the myoepithelial cells.", "contents": "Effects of sympathectomy on the in vivo alpha and beta-responses of the parotid gland. Salivary secretion in response to noradrenaline and isoprenaline was measured in innervated and chronically sympathectomized parotid glands of the rat. In innervated glands, the responses to isoprenaline lasted longer than those to noradrenaline. Chronic sympathetic denervation enhanced the responses to both noradrenaline and isoprenaline. The magnitude of the supersensitivity to isoprenaline was related to the dose and the time at which the responses were analyzed. Supersensitivity was greater for the initial than for the total secretion elicited by isoprenaline. Propranolol (1 mg/kg) and phentolamine (5 mg/kg) were used in order to determine the relative participation of alpha and beta-adrenoceptors in the enhanced responses to isoprenaline. The results suggest that postjunctional supersensitivity for the secretory responses of this organ to isoprenaline is mainly mediated through beta-adrenoceptors of the secretory cells and alpha-adrenoceptors of the myoepithelial cells."}
{"id": "PMID:228211", "title": "Effects of sympathectomy on the in vitro alpha and beta-responses of the parotid gland.", "content": "Amylase and K+ resease were measured in slices obtained from innervated and sympathetically denervated rat parotid glands. Amylase release induced by noradrenaline was found to be increased after chronic denervation. The postjunctional component of supersensitivity to noradrenaline was evidenced by an increase in the maximal response to this agonist. The maximal response of denervated glands was blocked by propranolol 10(-5) M. On the other hand, chronic denervation did not modify the alpha-adrenoceptor-mediated response, K+ release, either in the presence or in the absence of ouabain. It is concluded that, after sympathetic denervation, postjunctional supersensitivity develops for the beta-adrenoceptor-mediated but not for the alpha-adrenoceptors-mediated effects of noradrenaline.", "contents": "Effects of sympathectomy on the in vitro alpha and beta-responses of the parotid gland. Amylase and K+ resease were measured in slices obtained from innervated and sympathetically denervated rat parotid glands. Amylase release induced by noradrenaline was found to be increased after chronic denervation. The postjunctional component of supersensitivity to noradrenaline was evidenced by an increase in the maximal response to this agonist. The maximal response of denervated glands was blocked by propranolol 10(-5) M. On the other hand, chronic denervation did not modify the alpha-adrenoceptor-mediated response, K+ release, either in the presence or in the absence of ouabain. It is concluded that, after sympathetic denervation, postjunctional supersensitivity develops for the beta-adrenoceptor-mediated but not for the alpha-adrenoceptors-mediated effects of noradrenaline."}
{"id": "PMID:228212", "title": "Indirect evidence for presynaptic location of opiate receptors on chemosensitive primary sensory neurones.", "content": "1. Rats were pretreated with 50 mg/kg s.c. capsaicin or solvent on the second day of life; 5 months later 3H-diprenorphine binding to homogenates of the whole spinal cord or of the upper dorsal horn of the spinal cord was investigated. 2. Capsaicin pretreatment resulted in a 17% decrease of opiate binding sites in the whole spinal cord and a 37% decrease in the upper dorsal horn with no change in their affinity. 3. Since neonatal capsaicin pretreatment causes degeneration of chemosensitive primary sensory neurones it is concluded that some opiate receptors are located presynaptically on the central terminals of these neurones.", "contents": "Indirect evidence for presynaptic location of opiate receptors on chemosensitive primary sensory neurones. 1. Rats were pretreated with 50 mg/kg s.c. capsaicin or solvent on the second day of life; 5 months later 3H-diprenorphine binding to homogenates of the whole spinal cord or of the upper dorsal horn of the spinal cord was investigated. 2. Capsaicin pretreatment resulted in a 17% decrease of opiate binding sites in the whole spinal cord and a 37% decrease in the upper dorsal horn with no change in their affinity. 3. Since neonatal capsaicin pretreatment causes degeneration of chemosensitive primary sensory neurones it is concluded that some opiate receptors are located presynaptically on the central terminals of these neurones."}
{"id": "PMID:228214", "title": "Intraneural ganglion of the common peroneal nerve.", "content": "The authors report a fifteen-year-old patient with an intraneural ganglion cyst of the common peroneal nerve, with paralysis of the anterior tibial muscles which was subacute in onset. The lesion was radically removed using microtechniques. Such a purely intraneural location has rarely been described. The use of the surgical microscope and pathological study of the peroneal articular branches allows one to reject the possible synovial origin of this lesion. The different hypotheses regarding aetiology are discussed, as well as the possible lines of treatment.", "contents": "Intraneural ganglion of the common peroneal nerve. The authors report a fifteen-year-old patient with an intraneural ganglion cyst of the common peroneal nerve, with paralysis of the anterior tibial muscles which was subacute in onset. The lesion was radically removed using microtechniques. Such a purely intraneural location has rarely been described. The use of the surgical microscope and pathological study of the peroneal articular branches allows one to reject the possible synovial origin of this lesion. The different hypotheses regarding aetiology are discussed, as well as the possible lines of treatment."}
{"id": "PMID:228215", "title": "Classification of tumours in the sellar region using CT and encephalotomography.", "content": "Tumours in the sellar region may still present diagnostic problems. We therefore compared encephalotomographic and CT findings in sellar tumours and 91 patients were examined by both methods. For clinical purposes and operative treatment the degree of compression of the hypothalamus is of great importance. Encephalotomographic and CT findings are analysed and demonstrated. In cases of density differences between tumour and brain tissue shown by contrast enhancement, more information on the inner structure of a tumour (cystic or solid) can be obtained by computerized tomography. But if these are no density differences or/and contrast enhancement, tumour diagnosis is made easier by encephalotomography because of the great efficiency of this method.", "contents": "Classification of tumours in the sellar region using CT and encephalotomography. Tumours in the sellar region may still present diagnostic problems. We therefore compared encephalotomographic and CT findings in sellar tumours and 91 patients were examined by both methods. For clinical purposes and operative treatment the degree of compression of the hypothalamus is of great importance. Encephalotomographic and CT findings are analysed and demonstrated. In cases of density differences between tumour and brain tissue shown by contrast enhancement, more information on the inner structure of a tumour (cystic or solid) can be obtained by computerized tomography. But if these are no density differences or/and contrast enhancement, tumour diagnosis is made easier by encephalotomography because of the great efficiency of this method."}
{"id": "PMID:228216", "title": "Radiotherapy of intracranial astrocytomas: analysis of 417 cases treated from 1960 through 1969.", "content": "In a review of 417 intracranial astrocytomas treated radiotherapeutically at the Mayo Clinic from 1960 through 1969, the well-known correlation of tumor grade with survival was verified. Totally unexpected was the finding that age was fully as important a discriminant as tumor grade. Another unexpected finding was that patients treated with biopsy only followed by radiation therapy did as well as or slightly better than those subjected to resection followed by postoperative radiotherapy. We could not verify the importance to survival of either large dose or large volume radiotherapy, which has been emphasized by some. Patients receiving less than 1400 rets did just as well as or slightly better than those receiving more than 1400 rets. With low grade astrocytomas, survival beyond 4 years was significantly worse (higher death rates) in the group receiving more than 1400 rets. This suggested the possibility of radiation damage with delayed manifestations. We also could not verify an increased effectiveness for the generally accepted use of total brain irradiation for high grade gliomas.", "contents": "Radiotherapy of intracranial astrocytomas: analysis of 417 cases treated from 1960 through 1969. In a review of 417 intracranial astrocytomas treated radiotherapeutically at the Mayo Clinic from 1960 through 1969, the well-known correlation of tumor grade with survival was verified. Totally unexpected was the finding that age was fully as important a discriminant as tumor grade. Another unexpected finding was that patients treated with biopsy only followed by radiation therapy did as well as or slightly better than those subjected to resection followed by postoperative radiotherapy. We could not verify the importance to survival of either large dose or large volume radiotherapy, which has been emphasized by some. Patients receiving less than 1400 rets did just as well as or slightly better than those receiving more than 1400 rets. With low grade astrocytomas, survival beyond 4 years was significantly worse (higher death rates) in the group receiving more than 1400 rets. This suggested the possibility of radiation damage with delayed manifestations. We also could not verify an increased effectiveness for the generally accepted use of total brain irradiation for high grade gliomas."}
{"id": "PMID:228217", "title": "Simian virus 40-related DNA sequences in a human brain tumor.", "content": "Papovaviruses can induce experimental brain neoplasms in animals, and some papovaviruses have been implicated in the formation of various human tumors. We examined a series of seven human brain tumors removed at craniotomy for the presence of viral DNA sequences by the technique of DNA-DNA hybridization. Simian virus 40 (SV40) DNA was labeled in vitro and used as a \"probe\" for detecting related DNA sequences in cellular DNA extracted from brain tumors. SV40-related DNA sequences were found in DNA extracted from one tumor, a glioblastoma multiforme. It was calculated that approximately 1.2 viral genome equivalents per diploid cell were present in the tumor. Since the rate of reassociation of the probe deviated from ideal second-order kinetics, it is surmised that either only a portion of the SV40 genome was present in tumor cells or, alternatively, that the probe detected a related human papovavirus.", "contents": "Simian virus 40-related DNA sequences in a human brain tumor. Papovaviruses can induce experimental brain neoplasms in animals, and some papovaviruses have been implicated in the formation of various human tumors. We examined a series of seven human brain tumors removed at craniotomy for the presence of viral DNA sequences by the technique of DNA-DNA hybridization. Simian virus 40 (SV40) DNA was labeled in vitro and used as a \"probe\" for detecting related DNA sequences in cellular DNA extracted from brain tumors. SV40-related DNA sequences were found in DNA extracted from one tumor, a glioblastoma multiforme. It was calculated that approximately 1.2 viral genome equivalents per diploid cell were present in the tumor. Since the rate of reassociation of the probe deviated from ideal second-order kinetics, it is surmised that either only a portion of the SV40 genome was present in tumor cells or, alternatively, that the probe detected a related human papovavirus."}
{"id": "PMID:228218", "title": "Electron microscopy of skin and peripheral blood lymphocytes in infantile (Santavuori) neuronal ceroid lipofuscinosis.", "content": "Skin punch biopsies and peripheral blood lymphocyte preparations from two siblings with early infantile (Santavuori) neuronal ceroid lipofuscinosis have been examined by electron microscopy. In both cases characteristic osmiophilic inclusion bodies were found in various cells in the skin and in lymphocytes. In one case, lymphocyte inclusions were detected before the onset of any symptoms as a result of a family study. This indicates the possibility of screening lymphocytes of siblings of affected patients as a result of a family study. This indicates the possibility of screening lymphocytes of siblings of affected patients with a view to early detection of the disorder.", "contents": "Electron microscopy of skin and peripheral blood lymphocytes in infantile (Santavuori) neuronal ceroid lipofuscinosis. Skin punch biopsies and peripheral blood lymphocyte preparations from two siblings with early infantile (Santavuori) neuronal ceroid lipofuscinosis have been examined by electron microscopy. In both cases characteristic osmiophilic inclusion bodies were found in various cells in the skin and in lymphocytes. In one case, lymphocyte inclusions were detected before the onset of any symptoms as a result of a family study. This indicates the possibility of screening lymphocytes of siblings of affected patients as a result of a family study. This indicates the possibility of screening lymphocytes of siblings of affected patients with a view to early detection of the disorder."}
{"id": "PMID:228220", "title": "[Trophoblastic disease in one ovum in a twin pregnancy].", "content": "A case of trophoblastic disease in a twin pregnancy is described from its diagnosis to follow-up after emptying of the uterine cavity. The possible causes of trophoblastic disease are discussed.", "contents": "[Trophoblastic disease in one ovum in a twin pregnancy]. A case of trophoblastic disease in a twin pregnancy is described from its diagnosis to follow-up after emptying of the uterine cavity. The possible causes of trophoblastic disease are discussed."}
{"id": "PMID:228221", "title": "False-positive amniotic fluid cytology in a parturient with active genital herpes infection at term.", "content": "A patient who developed genital herpes infection diagnosed at 37 weeks' gestation is presented. Amniocentesis performed at 38 weeks' gestation revealed herpetic changes in fetal cells. Subsequent amniotic fluid viral culture was negative. The infant was delivered by elective primary cesarean section at 39 weeks' gestation, demonstrated no evidence of herpetic infection, and was well at a 3-month follow-up examination. Positive cytologic changes seen in epithelial cells obtained by amniocentesis do not necessarily indicate intrauterine infection of the fetus. Cytologic changes alone are inadequate, and viral isolation by culture or by immunofluorescence should be required before prophylactic cesarean section is abandoned in the treatment of the parturient with active genital herpes infection near term.", "contents": "False-positive amniotic fluid cytology in a parturient with active genital herpes infection at term. A patient who developed genital herpes infection diagnosed at 37 weeks' gestation is presented. Amniocentesis performed at 38 weeks' gestation revealed herpetic changes in fetal cells. Subsequent amniotic fluid viral culture was negative. The infant was delivered by elective primary cesarean section at 39 weeks' gestation, demonstrated no evidence of herpetic infection, and was well at a 3-month follow-up examination. Positive cytologic changes seen in epithelial cells obtained by amniocentesis do not necessarily indicate intrauterine infection of the fetus. Cytologic changes alone are inadequate, and viral isolation by culture or by immunofluorescence should be required before prophylactic cesarean section is abandoned in the treatment of the parturient with active genital herpes infection near term."}
{"id": "PMID:228222", "title": "Herpesvirus hominis type 1: a summary of structure, composition, growth cycle, and cytopathogenic effects.", "content": "The widespread occurrence of localized herpetic infections constitutes a significant problem for the dental profession. A summary of the structure and composition, growth cycle, and cytopathogenic effects of Herpesvirus hominis Type 1 is offered with the hope that a greater understanding of herpetic infections will ensue.", "contents": "Herpesvirus hominis type 1: a summary of structure, composition, growth cycle, and cytopathogenic effects. The widespread occurrence of localized herpetic infections constitutes a significant problem for the dental profession. A summary of the structure and composition, growth cycle, and cytopathogenic effects of Herpesvirus hominis Type 1 is offered with the hope that a greater understanding of herpetic infections will ensue."}
{"id": "PMID:228223", "title": "Fractures of the malar bone. Follow-up study based upon a questionnaire.", "content": "During the years 1969-1976 214 patients with malar bone fractures were treated. A retrospective study was carried out and a follow-up by the aid of a questionnaire. The clinical judgement at 1 week after surgery showed good results. The follow-up study revealed, however, a poorer picture. Among the surgically treated patients who answered the questionnaire, 89 of 143 reported different complaints. Anaesthesia in the check and diplopia were the most common complaints. It seems anyhow that the process of regeneration of the sensible nerve takes longer than predicted. The pre-operative evaluation of the eye motility is of utmost importance.", "contents": "Fractures of the malar bone. Follow-up study based upon a questionnaire. During the years 1969-1976 214 patients with malar bone fractures were treated. A retrospective study was carried out and a follow-up by the aid of a questionnaire. The clinical judgement at 1 week after surgery showed good results. The follow-up study revealed, however, a poorer picture. Among the surgically treated patients who answered the questionnaire, 89 of 143 reported different complaints. Anaesthesia in the check and diplopia were the most common complaints. It seems anyhow that the process of regeneration of the sensible nerve takes longer than predicted. The pre-operative evaluation of the eye motility is of utmost importance."}
{"id": "PMID:228227", "title": "[Relations of HLA A2, A3, B12 antigens, and A2-B12 supposed haplotype association, with latent herpes virus infection in patients with chronic renal disease (author's transl)].", "content": "Comparison of 105 patients suffering of chronical renal failure with 108 normal persons showed that, in the former group, a relation could be established between HLA A2, A3, and B12 histocompatibility antigens as well as haplotype association A2-B12, and chronic infection by herpes virus. The high number of herpes virus observed in patient group bearing the BW 35 antigen was discussed.", "contents": "[Relations of HLA A2, A3, B12 antigens, and A2-B12 supposed haplotype association, with latent herpes virus infection in patients with chronic renal disease (author's transl)]. Comparison of 105 patients suffering of chronical renal failure with 108 normal persons showed that, in the former group, a relation could be established between HLA A2, A3, and B12 histocompatibility antigens as well as haplotype association A2-B12, and chronic infection by herpes virus. The high number of herpes virus observed in patient group bearing the BW 35 antigen was discussed."}
{"id": "PMID:228225", "title": "Malignant fibrous histiocytoma of the larynx.", "content": "Fibrous histiocytoma is a rare mesenchymal tumor. The origin is believed to be a pleuri-potential cell, histiocytic in type, which can evolve into a facultative fibroblast under certain conditions. A case of a malignant fibrous histiocytoma in the subglottic larynx is reported. At present, the clinical behavior and degree of malignancy cannot be predicted. It appears that wide, local excision of the tumor with a margin of normal tissue is the treatment of choice. Regional block dissection of lymph nodes is not indicated unless clinically palpable nodes are present.", "contents": "Malignant fibrous histiocytoma of the larynx. Fibrous histiocytoma is a rare mesenchymal tumor. The origin is believed to be a pleuri-potential cell, histiocytic in type, which can evolve into a facultative fibroblast under certain conditions. A case of a malignant fibrous histiocytoma in the subglottic larynx is reported. At present, the clinical behavior and degree of malignancy cannot be predicted. It appears that wide, local excision of the tumor with a margin of normal tissue is the treatment of choice. Regional block dissection of lymph nodes is not indicated unless clinically palpable nodes are present."}
{"id": "PMID:228224", "title": "Sarcomatous degeneration in a nasopharyngeal angiofibroma.", "content": "Malignant degeneration in a juvenile nasopharyngeal angiofibroma has been reported in the literature in only four patients. All of these persons had been previously treated for cure with gamma irradiation. The case report of a 47-year-old man with a 31-year history of nasal obstruction is presented. A recurrence excised 18 months after initial removal of an angiofibroma revealed the surprising diagnosis of fibrosarcoma.", "contents": "Sarcomatous degeneration in a nasopharyngeal angiofibroma. Malignant degeneration in a juvenile nasopharyngeal angiofibroma has been reported in the literature in only four patients. All of these persons had been previously treated for cure with gamma irradiation. The case report of a 47-year-old man with a 31-year history of nasal obstruction is presented. A recurrence excised 18 months after initial removal of an angiofibroma revealed the surprising diagnosis of fibrosarcoma."}
{"id": "PMID:228226", "title": "Recurrent adenoid cystic carcinoma of the trachea: intraluminal radiotherapy.", "content": "Malignant neoplasms of the trachea are rare lesions, of which adenoid cystic carcinoma constitutes 30%. A case of extensive tumor recurrent after primary radiotherapy is presented. Surgical resection and radioisotope implantation were impossible. A method was devised for placement of intraluminal iridium 192 by casting six small hollow plastic tubes to the outer circumference of a Silastic endotracheal tube. This was an easy, safe, and effective method of delivering radiation to the trachea while sparing other vital structures and organs. Excellent tumor response and palliation were achieved. The literature is reviewed and the problems in diagnosis of this tumor are discussed. A comprehensive plan for early diagnosis is presented. All current methods of treatment are discussed, and the need for aggressive surgical management is stressed.", "contents": "Recurrent adenoid cystic carcinoma of the trachea: intraluminal radiotherapy. Malignant neoplasms of the trachea are rare lesions, of which adenoid cystic carcinoma constitutes 30%. A case of extensive tumor recurrent after primary radiotherapy is presented. Surgical resection and radioisotope implantation were impossible. A method was devised for placement of intraluminal iridium 192 by casting six small hollow plastic tubes to the outer circumference of a Silastic endotracheal tube. This was an easy, safe, and effective method of delivering radiation to the trachea while sparing other vital structures and organs. Excellent tumor response and palliation were achieved. The literature is reviewed and the problems in diagnosis of this tumor are discussed. A comprehensive plan for early diagnosis is presented. All current methods of treatment are discussed, and the need for aggressive surgical management is stressed."}
{"id": "PMID:228233", "title": "Lipid and lipoprotein tracking in children.", "content": "Prospective studies in adults reveal that CHD risk is continuously related to total and LDL cholesterol levels (positively) and to HDL cholesterol levels (inversely) throughout their entire distribution. Such findings raise the possibility that children who tend to track in the lowest and highest decile for total and LDL cholesterol may mature to become adults respectively at reduced and increased CHD risk. Children who tend to track in the lowest and highest deciles for HDL cholesterol may also mature to become adults respectively at increased and reduced CHD risk. Although the degree of tracking at either extreme of the distribution, and for the group as a whole, appears to have adquate cohesiveness to be useful for prediction of future lipid and lipoprotein levels, individual children at the extremes of the distributions will need to be followed over longer periods of time, to identify the continuity of childhood and adult values, and eventual CHD risk.", "contents": "Lipid and lipoprotein tracking in children. Prospective studies in adults reveal that CHD risk is continuously related to total and LDL cholesterol levels (positively) and to HDL cholesterol levels (inversely) throughout their entire distribution. Such findings raise the possibility that children who tend to track in the lowest and highest decile for total and LDL cholesterol may mature to become adults respectively at reduced and increased CHD risk. Children who tend to track in the lowest and highest deciles for HDL cholesterol may also mature to become adults respectively at increased and reduced CHD risk. Although the degree of tracking at either extreme of the distribution, and for the group as a whole, appears to have adquate cohesiveness to be useful for prediction of future lipid and lipoprotein levels, individual children at the extremes of the distributions will need to be followed over longer periods of time, to identify the continuity of childhood and adult values, and eventual CHD risk."}
{"id": "PMID:228234", "title": "Plasma glucocorticoid and adrenocorticotropin concentrations measured serially in growth-retarded fetal lambs.", "content": "We studied the fetal pituitrary-adrenal axis in 9 growth retarded fetal lambs by serially measuring plasma glucocorticoids and ACTH concentrations from 115 to 140 days of gestation and adrenal blood flow at 138 days of gestation. At each gestational age period studied, plasma glucocorticoid and ACTH concentrations were similar in both growth retarded and control fetuses (Figs. 1, 2). However, ACTH concentration tended to be higher in the last 20 days of gestation in the growth retarded fetuses. This resulted in a significantly lower glucocorticoid/ACTH ratio between 121 to 130 days of gestation in the growth retarded fetal lambs as compared to the control fetuses (212 +/- 111 vs. 1042 +/- 257). The glucocorticoid/ACTH ratio in the growth retarded fetuses became similar to the ratio of the control fetuses at 131 to 140 days (445 +/- 145 vs. 554 +/- 182). Adrenal blood flow was significantly increased at term in the the growth retarded fetuses (535 +/- 87 vs. 302 +/- 40 ml/min/100g). These data indicate that the pattern of maturation of the fetal adrenal gland in the growth retarded fetal lamb is similar to that of the normal sized fetus. Because of the increased adrenal blood flow observed at 138 days of gestation, there is a suggestion of a decreased sensitivity to ACTH in these animals.", "contents": "Plasma glucocorticoid and adrenocorticotropin concentrations measured serially in growth-retarded fetal lambs. We studied the fetal pituitrary-adrenal axis in 9 growth retarded fetal lambs by serially measuring plasma glucocorticoids and ACTH concentrations from 115 to 140 days of gestation and adrenal blood flow at 138 days of gestation. At each gestational age period studied, plasma glucocorticoid and ACTH concentrations were similar in both growth retarded and control fetuses (Figs. 1, 2). However, ACTH concentration tended to be higher in the last 20 days of gestation in the growth retarded fetuses. This resulted in a significantly lower glucocorticoid/ACTH ratio between 121 to 130 days of gestation in the growth retarded fetal lambs as compared to the control fetuses (212 +/- 111 vs. 1042 +/- 257). The glucocorticoid/ACTH ratio in the growth retarded fetuses became similar to the ratio of the control fetuses at 131 to 140 days (445 +/- 145 vs. 554 +/- 182). Adrenal blood flow was significantly increased at term in the the growth retarded fetuses (535 +/- 87 vs. 302 +/- 40 ml/min/100g). These data indicate that the pattern of maturation of the fetal adrenal gland in the growth retarded fetal lamb is similar to that of the normal sized fetus. Because of the increased adrenal blood flow observed at 138 days of gestation, there is a suggestion of a decreased sensitivity to ACTH in these animals."}
{"id": "PMID:228236", "title": "Effect of sleep state on chest distortion and on the ventilatory response to CO2 in neonates.", "content": "In 10 preterm and 10 term infants, the effect of sleep state on chest distortion and on the ventilatory response to CO2 was assessed. It was found that chest distortion and ventilatory response to CO2 were independent of sleep state. Chest distortion, however, was more frequent in preterm than in term infants. The authors suggest that the increased prevalence of chest distortion in preterm infants is related to their highly compliant chest wall rather than to differences in sleep state.", "contents": "Effect of sleep state on chest distortion and on the ventilatory response to CO2 in neonates. In 10 preterm and 10 term infants, the effect of sleep state on chest distortion and on the ventilatory response to CO2 was assessed. It was found that chest distortion and ventilatory response to CO2 were independent of sleep state. Chest distortion, however, was more frequent in preterm than in term infants. The authors suggest that the increased prevalence of chest distortion in preterm infants is related to their highly compliant chest wall rather than to differences in sleep state."}
{"id": "PMID:228238", "title": "Bactericidal and metabolic function of polymorphonuclear leukocytes.", "content": "The bactericidal and metabolic function of the phagocytic system requires integration of several complex humoral and cellular factors responding to different regulators. Polymorphonuclear leukocytes are highly mobile cells, capable of phagocytosis of bacteria or fungi with formation of a \"cellular digestive system\" containing reactive oxygen radicals, hydrogen ions, and digestive enzymes. The unique metabolism of oxygen in neutrophils results in release of energy as light (chemiluminescence) a response closely associated with microbiol killing. Neonatal neutrophils cope with normal bacterial challenges in vitro as efficiently as adult neutrophils; however, these cells have decreased capacity for locomotion, decreased deformability, decreased phagocytosis in low serum concentrations, and decreased chemiluminescence. These subtle defects in function can be amplified by exaggerated challenge which may be related to a higher incidence of sepsis during the neonatal period.", "contents": "Bactericidal and metabolic function of polymorphonuclear leukocytes. The bactericidal and metabolic function of the phagocytic system requires integration of several complex humoral and cellular factors responding to different regulators. Polymorphonuclear leukocytes are highly mobile cells, capable of phagocytosis of bacteria or fungi with formation of a \"cellular digestive system\" containing reactive oxygen radicals, hydrogen ions, and digestive enzymes. The unique metabolism of oxygen in neutrophils results in release of energy as light (chemiluminescence) a response closely associated with microbiol killing. Neonatal neutrophils cope with normal bacterial challenges in vitro as efficiently as adult neutrophils; however, these cells have decreased capacity for locomotion, decreased deformability, decreased phagocytosis in low serum concentrations, and decreased chemiluminescence. These subtle defects in function can be amplified by exaggerated challenge which may be related to a higher incidence of sepsis during the neonatal period."}
{"id": "PMID:228239", "title": "Defective oxidative metabolism in newborn neutrophils: discrepancy between superoxide anion and hydroxyl radical generation.", "content": "Investigation of oxidative metabolism in neutrophils (PMNs) from newborns was performed by measuring generation of superoxide anion (.O2-) and production of hydroxyl radical (.OH) in the resting state and after stimulation with opsonized zymosan or phorbol myristate acetate (PMA). Neutrophils from cord blood of ten term infants and normal adult controls were tested simultaneously. Cord PMNs generated significantly more .O2- than paired adult controls when stimulated with opsonized zymosan (P less than .01) and produced less .OH with PMA (P less than .005). When the amount of .O2- and .OH released by newborn PMNs with both stimuli was expressed as percent of values obtained from paired adult controls, there was a discrepancy in the generation of these two radicals: newborn PMNs produced relatively less .OH compared to .O2-. This decreased ability to produce .OH could underlie defective bactericidal activity in PMNs of neonates.", "contents": "Defective oxidative metabolism in newborn neutrophils: discrepancy between superoxide anion and hydroxyl radical generation. Investigation of oxidative metabolism in neutrophils (PMNs) from newborns was performed by measuring generation of superoxide anion (.O2-) and production of hydroxyl radical (.OH) in the resting state and after stimulation with opsonized zymosan or phorbol myristate acetate (PMA). Neutrophils from cord blood of ten term infants and normal adult controls were tested simultaneously. Cord PMNs generated significantly more .O2- than paired adult controls when stimulated with opsonized zymosan (P less than .01) and produced less .OH with PMA (P less than .005). When the amount of .O2- and .OH released by newborn PMNs with both stimuli was expressed as percent of values obtained from paired adult controls, there was a discrepancy in the generation of these two radicals: newborn PMNs produced relatively less .OH compared to .O2-. This decreased ability to produce .OH could underlie defective bactericidal activity in PMNs of neonates."}
{"id": "PMID:228242", "title": "Reciprocal responses to tilt of neurones within both fore- and hindlimb regions of Deiters' nucleus.", "content": "In decerebrate cats with cerebellum intact the frequency response of 102 neurons located within the lateral vestibular nucleus (LVN) to sinusoidal stimulation of vestibular receptors was analyzed. Positional sensitive units, showing a reciprocal pattern of response to lateral tilting, characterized by an excitation during ipsilateral and a depression during contralateral tilt, were equally found in the rostroventral (forelimb) and dorsocaudal (hindlimb) divisions of the LVN. No unit was found to be excited during both ipsilateral and contralateral tilts. A comparison between these findings and those reported in cerebellectomized preparations indicates that the reciprocal pattern of response to tilt of neurons, particularly located in the hindlimb region of the LVN, depends upon the anatomical integrity of the cerebellum.", "contents": "Reciprocal responses to tilt of neurones within both fore- and hindlimb regions of Deiters' nucleus. In decerebrate cats with cerebellum intact the frequency response of 102 neurons located within the lateral vestibular nucleus (LVN) to sinusoidal stimulation of vestibular receptors was analyzed. Positional sensitive units, showing a reciprocal pattern of response to lateral tilting, characterized by an excitation during ipsilateral and a depression during contralateral tilt, were equally found in the rostroventral (forelimb) and dorsocaudal (hindlimb) divisions of the LVN. No unit was found to be excited during both ipsilateral and contralateral tilts. A comparison between these findings and those reported in cerebellectomized preparations indicates that the reciprocal pattern of response to tilt of neurons, particularly located in the hindlimb region of the LVN, depends upon the anatomical integrity of the cerebellum."}
{"id": "PMID:228243", "title": "Effect of repetitive stimulation on the frog neuromuscular transmission.", "content": "Presynaptic and postsynaptic effects on the neuromuscular transmission were studied during 20 min of indirect stimulation at 10/s. During the 'facilitation' period, there was an increase in the quantal content, in the frequency of miniature endplate potentials and in their amplitude. All these parameters were decreased during the 'depression' period. Besides, the end-plate current (e.p.c.), recorded during this high rate of stimulation, increasingly lengthened. The falling phase of the e.p.c. was exponential during facilitation, while marked deviations from the exponential time course were observed during depression. The experiments showed that a possible change in the kinetics between the receptors and the mediator was not responsible for the lengthened time course of the e.p.c. Therefore, it is assumed that either the delayed diffusion of the transmitter from the synaptic cleft or an altered mechanism of the release of acetylcholine may be involved. The latter possibility is supported by a progressive prolongation of the synaptic delay, which was observed during a prolonged repetitive stimulation.", "contents": "Effect of repetitive stimulation on the frog neuromuscular transmission. Presynaptic and postsynaptic effects on the neuromuscular transmission were studied during 20 min of indirect stimulation at 10/s. During the 'facilitation' period, there was an increase in the quantal content, in the frequency of miniature endplate potentials and in their amplitude. All these parameters were decreased during the 'depression' period. Besides, the end-plate current (e.p.c.), recorded during this high rate of stimulation, increasingly lengthened. The falling phase of the e.p.c. was exponential during facilitation, while marked deviations from the exponential time course were observed during depression. The experiments showed that a possible change in the kinetics between the receptors and the mediator was not responsible for the lengthened time course of the e.p.c. Therefore, it is assumed that either the delayed diffusion of the transmitter from the synaptic cleft or an altered mechanism of the release of acetylcholine may be involved. The latter possibility is supported by a progressive prolongation of the synaptic delay, which was observed during a prolonged repetitive stimulation."}
{"id": "PMID:228245", "title": "[Immunological abnormalities in atopic dermatitis (author's transl)].", "content": "The humoral immunological abnormalities in atopic dermatitis (AD) are mainly represented by the increase of IgE. But high IgE levels are inconstant and non specific for AD. They may remain elevated during remission and their role in the pathogenesis is unclear. The origin of the stimulation of IgE-producing B lymphocytes could be a transcient deficiency of IgA in newborns or a defect of the T cell control. A defect of cell-mediated immunity has been clearly demonstrated by numerous in vitro studies indicating low percentages of E rosettes and low stimulation by mitogens. This defect could be a T suppressor cell defect. The correlations of these immunological abnormalities with the Sczentivanyi's theory as well as the role of immuno-pharmacological disturbances in the clinical picture and the possible new treatments of AD are discussed.", "contents": "[Immunological abnormalities in atopic dermatitis (author's transl)]. The humoral immunological abnormalities in atopic dermatitis (AD) are mainly represented by the increase of IgE. But high IgE levels are inconstant and non specific for AD. They may remain elevated during remission and their role in the pathogenesis is unclear. The origin of the stimulation of IgE-producing B lymphocytes could be a transcient deficiency of IgA in newborns or a defect of the T cell control. A defect of cell-mediated immunity has been clearly demonstrated by numerous in vitro studies indicating low percentages of E rosettes and low stimulation by mitogens. This defect could be a T suppressor cell defect. The correlations of these immunological abnormalities with the Sczentivanyi's theory as well as the role of immuno-pharmacological disturbances in the clinical picture and the possible new treatments of AD are discussed."}
{"id": "PMID:228246", "title": "Comparative study of papovavirus DNA: BKV(MM), BKV(WT) and SV40.", "content": "Extensive physical mapping revealed that approximately 90% of the genomes of BKV(prototype, WT) and BKV (MM strain) are identical or closely related. Nucleotide sequences of the non-homologous regions and a large portion of the homologous regions have been determined for both genomes. The coding sequence of small t antigen of BKV(MM) is 216 nucleotides shorter than that of BKV(WT), even though no differences in biological function of the t antigen was observed. Both genomes contain three similar sets of 44-61 base-pair repeated sequences. However, the DNA sequence of the tandem repeats is totally different between BKV (human cell as host) and SV40 (monkey cell as host). On the other hand, the region between the N-terminus of the T antigen genes and the origin of replication is dominated by a similar set of palindromic sequences in BKV and SV40 DNA. There is also extensive homology between the regions which code for proteins in BKV and SV40, suggesting a close evolutionary relationship.", "contents": "Comparative study of papovavirus DNA: BKV(MM), BKV(WT) and SV40. Extensive physical mapping revealed that approximately 90% of the genomes of BKV(prototype, WT) and BKV (MM strain) are identical or closely related. Nucleotide sequences of the non-homologous regions and a large portion of the homologous regions have been determined for both genomes. The coding sequence of small t antigen of BKV(MM) is 216 nucleotides shorter than that of BKV(WT), even though no differences in biological function of the t antigen was observed. Both genomes contain three similar sets of 44-61 base-pair repeated sequences. However, the DNA sequence of the tandem repeats is totally different between BKV (human cell as host) and SV40 (monkey cell as host). On the other hand, the region between the N-terminus of the T antigen genes and the origin of replication is dominated by a similar set of palindromic sequences in BKV and SV40 DNA. There is also extensive homology between the regions which code for proteins in BKV and SV40, suggesting a close evolutionary relationship."}
{"id": "PMID:228247", "title": "Nicking-closing enzyme is associated with SV40 DNA in vivo as a sodium dodecyl sulfate-resistant complex.", "content": "A fraction of the cellular nicking-closing (NC) enzyme cosediments with SV40 chromatin isolated after Triton X-100 treatment of infected cells nuclei. Extraction of viral DNA according to the Hirt procedure by treatment of infected cells with sodium dodecyl sulfate (SDS) followed by sedimentation in sucrose gradient to separate the DNA from the bulk of detergent also revealed NC activity associated with DNA. Reconstitution experiments showed that only prebinding of the NC enzyme to DNA protects it against irreversible inactivation by SDS. These results suggest that a fraction of the cellular NC activity is indeed associated with the viral chromosome in vivo.", "contents": "Nicking-closing enzyme is associated with SV40 DNA in vivo as a sodium dodecyl sulfate-resistant complex. A fraction of the cellular nicking-closing (NC) enzyme cosediments with SV40 chromatin isolated after Triton X-100 treatment of infected cells nuclei. Extraction of viral DNA according to the Hirt procedure by treatment of infected cells with sodium dodecyl sulfate (SDS) followed by sedimentation in sucrose gradient to separate the DNA from the bulk of detergent also revealed NC activity associated with DNA. Reconstitution experiments showed that only prebinding of the NC enzyme to DNA protects it against irreversible inactivation by SDS. These results suggest that a fraction of the cellular NC activity is indeed associated with the viral chromosome in vivo."}
{"id": "PMID:228248", "title": "Preferential in vitro assembly of nucleosome cores on some AT-rich regions of SV40 DNA.", "content": "We have found that nucleosomes reconstituted from histone octamers and SV40 DNA Form I by progressively decreasing the salt concentration from 2 M NaCl are formed preferentially around 0.27, 0.37, 0.50 and 0.85 on SV40 DNA (relative to the EcoRI site). When SV40 DNA Form III is used, the nucleosomes form mainly at 0.28, 0.38, 0.61 and 0.83. These sites are very close to both the sites of RNA chain initiation by calf thymus RNA polymerase B on SV40 DNA Form I (0.25, 0.35, 0.42 and 0.88) and the regions of the supercoiled DNA which are readily denaturable by T4 gene 32 protein (0.25, 0.47 and 0.88), and correspond to AT-rich regions as deduced from the nucleotide sequence of SV40 DNA. The physiologically important region around 0.67 is an unfavourable site for all three types of proteins, and corresponds to a GC-rich region surrounding a 17 base pair AT cluster.", "contents": "Preferential in vitro assembly of nucleosome cores on some AT-rich regions of SV40 DNA. We have found that nucleosomes reconstituted from histone octamers and SV40 DNA Form I by progressively decreasing the salt concentration from 2 M NaCl are formed preferentially around 0.27, 0.37, 0.50 and 0.85 on SV40 DNA (relative to the EcoRI site). When SV40 DNA Form III is used, the nucleosomes form mainly at 0.28, 0.38, 0.61 and 0.83. These sites are very close to both the sites of RNA chain initiation by calf thymus RNA polymerase B on SV40 DNA Form I (0.25, 0.35, 0.42 and 0.88) and the regions of the supercoiled DNA which are readily denaturable by T4 gene 32 protein (0.25, 0.47 and 0.88), and correspond to AT-rich regions as deduced from the nucleotide sequence of SV40 DNA. The physiologically important region around 0.67 is an unfavourable site for all three types of proteins, and corresponds to a GC-rich region surrounding a 17 base pair AT cluster."}
{"id": "PMID:228249", "title": "Polyoma virus. The early region and its T-antigens.", "content": "The DNA sequence of the early coding region of polyoma virus is presented. It consists of 2739 nucleotides. The sequence predicts that more than one reading frame can be used to code for the three known polyoma virus early proteins (designated small, middle and large T-antigens). From the DNA sequence, the 'splicing' signals used in the processing of viral RNA to functional messenger RNAs can be predicted, as well as the sizes and sequences of the three proteins. Other unusual aspects of the DNA sequence are noted. Comparisons are made between the DNA sequences and the predicted amino acid sequences of the respective large T-antigens of polyoma virus and the related virus Simian Virus (SV) 40.", "contents": "Polyoma virus. The early region and its T-antigens. The DNA sequence of the early coding region of polyoma virus is presented. It consists of 2739 nucleotides. The sequence predicts that more than one reading frame can be used to code for the three known polyoma virus early proteins (designated small, middle and large T-antigens). From the DNA sequence, the 'splicing' signals used in the processing of viral RNA to functional messenger RNAs can be predicted, as well as the sizes and sequences of the three proteins. Other unusual aspects of the DNA sequence are noted. Comparisons are made between the DNA sequences and the predicted amino acid sequences of the respective large T-antigens of polyoma virus and the related virus Simian Virus (SV) 40."}
{"id": "PMID:228250", "title": "Hybrid plasmids containing an active thymidine kinase gene of Herpes simplex virus 1.", "content": "The gene for the thymidine kinase (TK) of Herpes simplex virus type 1 (HSV-1) is located in the KpnI m and BamHI p fragments of the genome (Wigler et al., Cell 11, 223-232 (1977)). These fragments have been inserted into the EcoRI and BamHI sites, respectively, of plasmid pBR322, and propagated in E.coli. The TK gene contained in the recombinant plasmids was shown to be biologically active when introduced into TK- mouse L cells. Detailed restriction site maps of the BamHI p fragment have been constructed and the approximate location of the TK gene has been determined. Mouse cells transformed with cloned HSV-1 tk+ DNA produced HSV-1-specific thymidine kinase; superinfection with HSV-1 tk- virus increased the level of TK activity tenfold, suggesting that the BamHI p sequences present in transformed cells respond to virus-encoded regulatory gene product(s).", "contents": "Hybrid plasmids containing an active thymidine kinase gene of Herpes simplex virus 1. The gene for the thymidine kinase (TK) of Herpes simplex virus type 1 (HSV-1) is located in the KpnI m and BamHI p fragments of the genome (Wigler et al., Cell 11, 223-232 (1977)). These fragments have been inserted into the EcoRI and BamHI sites, respectively, of plasmid pBR322, and propagated in E.coli. The TK gene contained in the recombinant plasmids was shown to be biologically active when introduced into TK- mouse L cells. Detailed restriction site maps of the BamHI p fragment have been constructed and the approximate location of the TK gene has been determined. Mouse cells transformed with cloned HSV-1 tk+ DNA produced HSV-1-specific thymidine kinase; superinfection with HSV-1 tk- virus increased the level of TK activity tenfold, suggesting that the BamHI p sequences present in transformed cells respond to virus-encoded regulatory gene product(s)."}
{"id": "PMID:228251", "title": "Specific chemical labeling of DNA fragments.", "content": "We describe a simple method for specific chemical labeling of DNA fragments at their 3'-termini. The procedure includes enzymatic addition of 4-thiouridine, followed by reaction in mild non-denaturing conditions with the highly reactive alpha-haloacetamido derivatives of several chemical labels. The attached reporter molecule can be removed by extended treatment with beta-mercaptoethanol. Among the potential applications of this labeling method is the study of specific protein-DNA interactions in solution.", "contents": "Specific chemical labeling of DNA fragments. We describe a simple method for specific chemical labeling of DNA fragments at their 3'-termini. The procedure includes enzymatic addition of 4-thiouridine, followed by reaction in mild non-denaturing conditions with the highly reactive alpha-haloacetamido derivatives of several chemical labels. The attached reporter molecule can be removed by extended treatment with beta-mercaptoethanol. Among the potential applications of this labeling method is the study of specific protein-DNA interactions in solution."}
{"id": "PMID:228252", "title": "Replicative activity of histone-deficient SV40 chromatin.", "content": "Histone-deficient SV40 chromatin, selectively radiolabeled in the DNA following the addition of cycloheximide to infected monkey cells, was compared with the normal 55S viral chromatin for its ability to serve as a template for a subsequent round of replication. After the removal of cycloheximide, the 26S histone-deficient SV40 chromatin was converted to apparently normal 55S chromatin. During this conversion, the chromatin which sedimented at 26-40S failed to replicate whereas the 44-55S chromatin contained a large fraction (28%) of newly replicated DNA molecules. Thus, the DNA in the 26S histone-deficient 40S chromatin cannot replicate without the prior and/or concommitant addition of protein which increases its sedimentation rate to 41-55S. Nevertheless, when compared with normal 55S viral chromatin, the histone-deficient SV40 chromatin had nearly a 3-fold greater probability of functioning as a template for a subsequent round of replication.", "contents": "Replicative activity of histone-deficient SV40 chromatin. Histone-deficient SV40 chromatin, selectively radiolabeled in the DNA following the addition of cycloheximide to infected monkey cells, was compared with the normal 55S viral chromatin for its ability to serve as a template for a subsequent round of replication. After the removal of cycloheximide, the 26S histone-deficient SV40 chromatin was converted to apparently normal 55S chromatin. During this conversion, the chromatin which sedimented at 26-40S failed to replicate whereas the 44-55S chromatin contained a large fraction (28%) of newly replicated DNA molecules. Thus, the DNA in the 26S histone-deficient 40S chromatin cannot replicate without the prior and/or concommitant addition of protein which increases its sedimentation rate to 41-55S. Nevertheless, when compared with normal 55S viral chromatin, the histone-deficient SV40 chromatin had nearly a 3-fold greater probability of functioning as a template for a subsequent round of replication."}
{"id": "PMID:228253", "title": "Non-specific interactions of CRP from E. coli with native and denatured DNAs: control of binding by cAMP and cGMP and by cation concentration.", "content": "The cyclic adenosine 3',5'-monophosphate receptor protein of Escherichia coli (CRP) binds cooperatively to single- and double-stranded DNA. Binding data could be fitted to the model of McGhee and von Hippel (1) and show that neither strandedness of DNA, nor the effectors cAMP and cGMP or the ionic strength (KCl) do change appreciably the cooperativity parameter omega (omega approximately or equal to 100), and site size of DNA. Instead, distinctly different slopes were observed for the linear decrease of log K omega (a measure of the overall affinity) as a function of log (K+). From these double-log plots (2), the number of cations released and the non-electrostatic contributions to the binding free energy could be determined. Binding of CRP to single-stranded DNA is slightly favored under physiological ionic conditions (0.15-0.20 M), but such a preferential binding is almost abolished in the presence of cAMP which increases the strength of the interaction of the protein with both forms of DNA. CGMP does not change the binding properties and interactions of CRP with DNA. These observations do not support the proposal that the cAMP-CRP complex could stimulate transcription via some \"melting\" property unless its interactions be dramatically changed when it binds specifically to promoter DNA.", "contents": "Non-specific interactions of CRP from E. coli with native and denatured DNAs: control of binding by cAMP and cGMP and by cation concentration. The cyclic adenosine 3',5'-monophosphate receptor protein of Escherichia coli (CRP) binds cooperatively to single- and double-stranded DNA. Binding data could be fitted to the model of McGhee and von Hippel (1) and show that neither strandedness of DNA, nor the effectors cAMP and cGMP or the ionic strength (KCl) do change appreciably the cooperativity parameter omega (omega approximately or equal to 100), and site size of DNA. Instead, distinctly different slopes were observed for the linear decrease of log K omega (a measure of the overall affinity) as a function of log (K+). From these double-log plots (2), the number of cations released and the non-electrostatic contributions to the binding free energy could be determined. Binding of CRP to single-stranded DNA is slightly favored under physiological ionic conditions (0.15-0.20 M), but such a preferential binding is almost abolished in the presence of cAMP which increases the strength of the interaction of the protein with both forms of DNA. CGMP does not change the binding properties and interactions of CRP with DNA. These observations do not support the proposal that the cAMP-CRP complex could stimulate transcription via some \"melting\" property unless its interactions be dramatically changed when it binds specifically to promoter DNA."}
{"id": "PMID:228254", "title": "The extraction from the blood of phosphate compounds by canine bone.", "content": "Uptake by bone of 99mTc-labeled pyrophosphate (PPi) and ethane-1-hydroxy-1,1-diphosphonate (EHDP) involves passage through capillaries in the Haversian system, extracellular fluid space, and membrane of osteoblasts before adsorption onto available apatite surfaces. Passage through capillaries was studied by the outflow-dilution technique in a canine tibia model in mongrel dogs. 51Cr-labeled albumin (nondiffusible reference tracer), sucrose (diffusible reference tracer), PPi, and EHDP were injected into the isolated nutrient tibial artery. Blood was collected from the ipsilateral femoral vein every 15 sec for 2 min. Emax, the apparent extraction at the time of the peaks of the dilution curves, is influenced little by back diffusion; for PP, Emax (mean +/- SD) = 0.42 +/- 0.08 (N = 4); for EHDP, Emax = 0.27 +/- 0.05 (N = 10). Net extraction (apparent fractional retention by bone at 2 min) was 0.36 +/- 0.1 for PP. Emax for 85Sr chloride and 18F sodium in our laboratory is 0.69 +/- 0.11 (N = 14) and 0.70 +/- 0.008 (N = 9), respectively. Permeabilities (P) were calculated by PS = -Fs loge (1-Emax), where Fs = plasma flow and S = capillary surface; the ratio of P for EHDP to P for sucrose was 0.71 which is similar to the ratio of diffusion coefficients, 0.78. The data suggest that EHDP and probably also PPi pass through the capillaries by passive diffusion. As expected, the extraction through capillary walls for EHDP and PPi was lower than that for 85Sr and 18F because of their larger molecular size.", "contents": "The extraction from the blood of phosphate compounds by canine bone. Uptake by bone of 99mTc-labeled pyrophosphate (PPi) and ethane-1-hydroxy-1,1-diphosphonate (EHDP) involves passage through capillaries in the Haversian system, extracellular fluid space, and membrane of osteoblasts before adsorption onto available apatite surfaces. Passage through capillaries was studied by the outflow-dilution technique in a canine tibia model in mongrel dogs. 51Cr-labeled albumin (nondiffusible reference tracer), sucrose (diffusible reference tracer), PPi, and EHDP were injected into the isolated nutrient tibial artery. Blood was collected from the ipsilateral femoral vein every 15 sec for 2 min. Emax, the apparent extraction at the time of the peaks of the dilution curves, is influenced little by back diffusion; for PP, Emax (mean +/- SD) = 0.42 +/- 0.08 (N = 4); for EHDP, Emax = 0.27 +/- 0.05 (N = 10). Net extraction (apparent fractional retention by bone at 2 min) was 0.36 +/- 0.1 for PP. Emax for 85Sr chloride and 18F sodium in our laboratory is 0.69 +/- 0.11 (N = 14) and 0.70 +/- 0.008 (N = 9), respectively. Permeabilities (P) were calculated by PS = -Fs loge (1-Emax), where Fs = plasma flow and S = capillary surface; the ratio of P for EHDP to P for sucrose was 0.71 which is similar to the ratio of diffusion coefficients, 0.78. The data suggest that EHDP and probably also PPi pass through the capillaries by passive diffusion. As expected, the extraction through capillary walls for EHDP and PPi was lower than that for 85Sr and 18F because of their larger molecular size."}
{"id": "PMID:228260", "title": "[Systematic evaluation of 8 arginine vasopressin and neurophysins plasma levels in 10 patients with oat cells carcinoma of the lung (author's transl)].", "content": "Plasma AVP level, neurophysins and osmolality have been measured in 10 patients with oat cell carcinoma of the lung but without any biological signs of syndrome of inappropriate secretion of ADH (SIADH), before and 15 mn after an intravenous injection of Ethanol. No statistically significant difference was noted in the AVP, neurophysins and osmolality values between 10 patients with asymptomatic oat cell carcinoma and control population (10 normal volunteers, 12 patients with non neoplasic lung pathology and 10 patients with different lung carcinoma). We concluded that AVP and neurophysins cannot be considered as a good tumoral marker in the detection of oat cell carcinoma of the lung.", "contents": "[Systematic evaluation of 8 arginine vasopressin and neurophysins plasma levels in 10 patients with oat cells carcinoma of the lung (author's transl)]. Plasma AVP level, neurophysins and osmolality have been measured in 10 patients with oat cell carcinoma of the lung but without any biological signs of syndrome of inappropriate secretion of ADH (SIADH), before and 15 mn after an intravenous injection of Ethanol. No statistically significant difference was noted in the AVP, neurophysins and osmolality values between 10 patients with asymptomatic oat cell carcinoma and control population (10 normal volunteers, 12 patients with non neoplasic lung pathology and 10 patients with different lung carcinoma). We concluded that AVP and neurophysins cannot be considered as a good tumoral marker in the detection of oat cell carcinoma of the lung."}
{"id": "PMID:228261", "title": "[Endobronchial Abrikosov's tumor. Two new cases associated to malignant tumors].", "content": "Endobronchial localizations of the granular cell tumours or Abrikossoff's tumour are very rare (6%) but their association with malignant tumours is exceptional and perhaps fortuitous. The clinical manifestations are generally the consequence of bronchial erosion and blocking. Bronchial endoscopy is the essential examination which allows the tumour to be seen and a biopsy to be made. Pathological examination confirms the diagnosis. The typicall cell of granular cell tumour is a large, polygonal one with finely granular eosinophilic cytoplasm and a small dark vesicular nucleus. Such cells are arranged in syncytial masses containing long, spindleshape cells with elongated nuclei. If the optical and elctron microscope description is well known, the histogenesis of the disease is still in dispute; the neurogenic origin seems to be the best one, but at present there is not enough evidence to make this assumption a certainty. Surgical exeresis is the only therapy to bring about a cure, but clinical supervision is necessary because of a possible relapse.", "contents": "[Endobronchial Abrikosov's tumor. Two new cases associated to malignant tumors]. Endobronchial localizations of the granular cell tumours or Abrikossoff's tumour are very rare (6%) but their association with malignant tumours is exceptional and perhaps fortuitous. The clinical manifestations are generally the consequence of bronchial erosion and blocking. Bronchial endoscopy is the essential examination which allows the tumour to be seen and a biopsy to be made. Pathological examination confirms the diagnosis. The typicall cell of granular cell tumour is a large, polygonal one with finely granular eosinophilic cytoplasm and a small dark vesicular nucleus. Such cells are arranged in syncytial masses containing long, spindleshape cells with elongated nuclei. If the optical and elctron microscope description is well known, the histogenesis of the disease is still in dispute; the neurogenic origin seems to be the best one, but at present there is not enough evidence to make this assumption a certainty. Surgical exeresis is the only therapy to bring about a cure, but clinical supervision is necessary because of a possible relapse."}
{"id": "PMID:228264", "title": "An interferon-induced phosphodiesterase degrading (2'-5') oligoisoadenylate and the C-C-A terminus of tRNA.", "content": "A phosphodiesterase characterized by a generally higher activity on 2'-5' than on 3'-5' phosphodiester bonds was isolated from mouse L cells treated with interferon. A similar enzyme was purified from mouse reticulocytes. The phosphodiesterase 2'-PDi splits the 2'-phosphate bond of pppA2'p5'A2'p5'A, the oligonucleotide activator of ribonuclease F. The level of phosphodiesterase 2'-PDi is increased by interferon treatment of L cells. The phosphodiesterase was also shown to degrade the C-C-A terminus of tRNA and to reduce the amino acid acceptance of tRNA in cell-free extracts, thereby causing a tRNA-reversible inhibition of mRNA translation.", "contents": "An interferon-induced phosphodiesterase degrading (2'-5') oligoisoadenylate and the C-C-A terminus of tRNA. A phosphodiesterase characterized by a generally higher activity on 2'-5' than on 3'-5' phosphodiester bonds was isolated from mouse L cells treated with interferon. A similar enzyme was purified from mouse reticulocytes. The phosphodiesterase 2'-PDi splits the 2'-phosphate bond of pppA2'p5'A2'p5'A, the oligonucleotide activator of ribonuclease F. The level of phosphodiesterase 2'-PDi is increased by interferon treatment of L cells. The phosphodiesterase was also shown to degrade the C-C-A terminus of tRNA and to reduce the amino acid acceptance of tRNA in cell-free extracts, thereby causing a tRNA-reversible inhibition of mRNA translation."}
{"id": "PMID:228265", "title": "Sequences of vesicular stomatitis virus RNA in the region coding for leader RNA, N protein mRNA, and their junction.", "content": "The RNAs extracted from purified preparations of the Indiana and New Jersey serotypes of vesicular stomatitis virus were polyadenylylated in vitro by using polynucleotide phosphorylase and sequence determination was carried out by the dideoxynucleotide method using reverse transcriptase and dT8AC primer. On both virus RNAs a short stretch of adenylic acid residues is present between the regions coding for the leader and N protein mRNAs. Other features of the RNA sequences of the two viruses are compared to each other and to published data.", "contents": "Sequences of vesicular stomatitis virus RNA in the region coding for leader RNA, N protein mRNA, and their junction. The RNAs extracted from purified preparations of the Indiana and New Jersey serotypes of vesicular stomatitis virus were polyadenylylated in vitro by using polynucleotide phosphorylase and sequence determination was carried out by the dideoxynucleotide method using reverse transcriptase and dT8AC primer. On both virus RNAs a short stretch of adenylic acid residues is present between the regions coding for the leader and N protein mRNAs. Other features of the RNA sequences of the two viruses are compared to each other and to published data."}
{"id": "PMID:228266", "title": "Integration of bovine leukemia virus DNA in the bovine genome.", "content": "DNA preparations from circulating leukocytes, lymph node tumors, and spleens of three bovine leukemia virus-infected cattle were fractionated by Cs2SO4/3,6-bis(acetatomercurimethyl)dioxane density gradient centrifugation. Bovine leukemia virus proviral sequences were found in large GC-rich fragments having a buoyant density in CsCl close to 1.708 g/cm3. Provirus integration, therefore, does not take place at random locations in the host genome, but in a specific class of DNA segments. Hybridization of cDNA synthesized on viral RNA to EcoRI and Xba I restriction fragments of the DNA from infected cells showed that: (i) only one copy of proviral DNA is integrated per haploid genome; (ii) different restriction patterns were found in the proviral DNAs present in the genomes of different animals, providing evidence for the existence of several strains or mutants; and (iii) different integration sites for the proviral DNA were found in the genome of different animals and of different infected cells in the same animal. The latter finding strongly suggests a polyclonal origin of bovine leukemia virus-infected cells.", "contents": "Integration of bovine leukemia virus DNA in the bovine genome. DNA preparations from circulating leukocytes, lymph node tumors, and spleens of three bovine leukemia virus-infected cattle were fractionated by Cs2SO4/3,6-bis(acetatomercurimethyl)dioxane density gradient centrifugation. Bovine leukemia virus proviral sequences were found in large GC-rich fragments having a buoyant density in CsCl close to 1.708 g/cm3. Provirus integration, therefore, does not take place at random locations in the host genome, but in a specific class of DNA segments. Hybridization of cDNA synthesized on viral RNA to EcoRI and Xba I restriction fragments of the DNA from infected cells showed that: (i) only one copy of proviral DNA is integrated per haploid genome; (ii) different restriction patterns were found in the proviral DNAs present in the genomes of different animals, providing evidence for the existence of several strains or mutants; and (iii) different integration sites for the proviral DNA were found in the genome of different animals and of different infected cells in the same animal. The latter finding strongly suggests a polyclonal origin of bovine leukemia virus-infected cells."}
{"id": "PMID:228267", "title": "Escherichia coli heat-labile enterotoxin: DNA-directed in vitro synthesis and structure.", "content": "Escherichia coli heat-labile enterotoxin was synthesized in a cell-free system directed by DNA of the plasmid P307. Synthesis of the toxin, assayed by the elongation induced in Chinese hamster ovary cells, was strongly stimulated by cyclic AMP and occurred at physiological levels of Mg2+ only when the polyamine spermidine was present. Activity was abolished by heat and antisera prepared against the enterotoxins of both E. coli P263 and Vibrio cholera. Tritium-labeled enterotoxin was purified by immunoprecipitation and examined by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. When gel slices were assayed for the ability to stimulate adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activity in erythrocyte ghosts, two peaks were found, one at Mr 26,000 and frequently, but not always, another at Mr 23,000. Detection of radiolabeled protein by fluorography and scintillation counting of gel slices revealed three prominent polypeptides, two corresponding to the peaks having adenylate cyclase-stimulating activity and a further one of Mr 11,500, identical to that of the cholera subunit B. The data suggest that the E. coli heat-labile enterotoxin synthesized in the cell-free system has a subunit structure.", "contents": "Escherichia coli heat-labile enterotoxin: DNA-directed in vitro synthesis and structure. Escherichia coli heat-labile enterotoxin was synthesized in a cell-free system directed by DNA of the plasmid P307. Synthesis of the toxin, assayed by the elongation induced in Chinese hamster ovary cells, was strongly stimulated by cyclic AMP and occurred at physiological levels of Mg2+ only when the polyamine spermidine was present. Activity was abolished by heat and antisera prepared against the enterotoxins of both E. coli P263 and Vibrio cholera. Tritium-labeled enterotoxin was purified by immunoprecipitation and examined by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. When gel slices were assayed for the ability to stimulate adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activity in erythrocyte ghosts, two peaks were found, one at Mr 26,000 and frequently, but not always, another at Mr 23,000. Detection of radiolabeled protein by fluorography and scintillation counting of gel slices revealed three prominent polypeptides, two corresponding to the peaks having adenylate cyclase-stimulating activity and a further one of Mr 11,500, identical to that of the cholera subunit B. The data suggest that the E. coli heat-labile enterotoxin synthesized in the cell-free system has a subunit structure."}
{"id": "PMID:228268", "title": "Origin of observed changes in 14N hyperfine interaction accompanying R leads to T transition in nitrosylhemoglobin.", "content": "Theoretical investigations of electronic distributions in eight different structural forms of nitrosylhemoglobin were carried out to study the changes in (14)N hyperfine interaction observed with the transition from R to T structures under the influence of inositol hexaphosphate or changing pH. Four of the eight forms studied consisted of protonated and deprotonated N(pros) in the proximal imidazole ligand with linear and bent Fe-N-O structures. Two other forms had a straight Fe-N-O structure and Fe-Im bond stretched by 0.5 and 1.0 A. The other two systems we have studied are five-liganded NO-heme with bent and straight Fe-N-O structures. Our investigations show that arrangements of energy levels did not differ significantly among all the structures, the unpaired electron always occupying an antibonding orbital with d(z)2 symmetry. The protonated and deprotonated systems with either linear or bent Fe-N-O structure showed substantial hyperfine interaction of the (14)N nuclei of the NO group and the N(epsilon) atom of the proximal imidazole, indicating that a 9-line electron spin resonance hyperfine pattern (R structure) would be expected in all four cases. On the other hand, the extensions of the Fe-Im bond produce a sizeable decrease in the (14)N(epsilon) hyperfine interaction, indicating that an extension beyond 1.0 A would provide a 3-line hyperfine pattern close to that found for the five-liganded NO-heme system. Our results thus provide quantitative support for the model of severe extension or cleavage of the Fe-N(epsilon) bond proposed in the literature for explaining the R-to-T transition of the alpha-chain of nitrosylhemoglobin.", "contents": "Origin of observed changes in 14N hyperfine interaction accompanying R leads to T transition in nitrosylhemoglobin. Theoretical investigations of electronic distributions in eight different structural forms of nitrosylhemoglobin were carried out to study the changes in (14)N hyperfine interaction observed with the transition from R to T structures under the influence of inositol hexaphosphate or changing pH. Four of the eight forms studied consisted of protonated and deprotonated N(pros) in the proximal imidazole ligand with linear and bent Fe-N-O structures. Two other forms had a straight Fe-N-O structure and Fe-Im bond stretched by 0.5 and 1.0 A. The other two systems we have studied are five-liganded NO-heme with bent and straight Fe-N-O structures. Our investigations show that arrangements of energy levels did not differ significantly among all the structures, the unpaired electron always occupying an antibonding orbital with d(z)2 symmetry. The protonated and deprotonated systems with either linear or bent Fe-N-O structure showed substantial hyperfine interaction of the (14)N nuclei of the NO group and the N(epsilon) atom of the proximal imidazole, indicating that a 9-line electron spin resonance hyperfine pattern (R structure) would be expected in all four cases. On the other hand, the extensions of the Fe-Im bond produce a sizeable decrease in the (14)N(epsilon) hyperfine interaction, indicating that an extension beyond 1.0 A would provide a 3-line hyperfine pattern close to that found for the five-liganded NO-heme system. Our results thus provide quantitative support for the model of severe extension or cleavage of the Fe-N(epsilon) bond proposed in the literature for explaining the R-to-T transition of the alpha-chain of nitrosylhemoglobin."}
{"id": "PMID:228269", "title": "Rate limitation of (Na+ + K+)-stimulated adenosinetriphosphatase by membrane acyl chain ordering.", "content": "A somatic cell mutant (CR1) of the Chinese hamster ovary cell line (CHO-K1) that is defective in the regulation of cholesterol biosynthesis can be grown under conditions in which plasma membranes from these cells display various cholesterol contents and acyl chain order parameters. The (Na+ + K+)-stimulated adenosinetriphosphatase (ATP phosphohydrolase, EC 3.6.1.3) from these cells was shown to vary in activity by a factor of 10 as the order parameter was varied, and the activity exhibited an exponential dependence on this parameter. Under these conditions the number of Na+,K+-ATPase molecules was shown to remain constant by affinity labeling with [gamma-32P]ATP in the absence of Na+. Control experiments showed that alteration in cholesterol content without change in order parameter did not result in altered enzyme activity. It is concluded that, under our conditions, the rate of catalysis by the Na+,K+-ATPase is determined by the order parameter. These studies suggest a physical mechanism by which variation of membrane lipid composition or other factors that determine membrane lipid acyl chain order parameter can result in variation in membrane enzyme activity.", "contents": "Rate limitation of (Na+ + K+)-stimulated adenosinetriphosphatase by membrane acyl chain ordering. A somatic cell mutant (CR1) of the Chinese hamster ovary cell line (CHO-K1) that is defective in the regulation of cholesterol biosynthesis can be grown under conditions in which plasma membranes from these cells display various cholesterol contents and acyl chain order parameters. The (Na+ + K+)-stimulated adenosinetriphosphatase (ATP phosphohydrolase, EC 3.6.1.3) from these cells was shown to vary in activity by a factor of 10 as the order parameter was varied, and the activity exhibited an exponential dependence on this parameter. Under these conditions the number of Na+,K+-ATPase molecules was shown to remain constant by affinity labeling with [gamma-32P]ATP in the absence of Na+. Control experiments showed that alteration in cholesterol content without change in order parameter did not result in altered enzyme activity. It is concluded that, under our conditions, the rate of catalysis by the Na+,K+-ATPase is determined by the order parameter. These studies suggest a physical mechanism by which variation of membrane lipid composition or other factors that determine membrane lipid acyl chain order parameter can result in variation in membrane enzyme activity."}
{"id": "PMID:228270", "title": "Sequential adsorption-electrophoresis: combined procedure for purification of calcium-dependent cyclic nucleotide phosphodiesterase.", "content": "A procedure for combined sequential affinity adsorption-electrophoresis has been devised. Its use for the rapid purification of a calcium-dependent cyclic nucleotide phosphodiesterase from bovine brain in high yield is described. In this procedure, proteins bound to a solid phase of calcium-dependent regulatory protein (CDR) linked to Sepharose 4B were electrophoretically eluted, concentrated, and separated, thus avoiding the large losses in activity incurred during attempts to purify further the phosphodiesterase eluted by conventional means. The highly purified phosphodiesterase prepared by this method was stable for months at -60 degrees C in the presence of glycerol. It has a higher affinity for cyclic GMP than for cyclic AMP, and hydrolysis of both substrates is stimulated 5- to 6-fold by calcium plus CDR. Factors that influence adsorption of the enzyme to CDR-Sepharose and selection of optimal conditions for electrophoresis were investigated. Sequential adsorption-electrophoresis should be generally useful in the purification of macromolecules for which affinity adsorbents are available. The procedures described here could be directly applicable to the purification of proteins that, like the phosphodiesterase, interact with CDR.", "contents": "Sequential adsorption-electrophoresis: combined procedure for purification of calcium-dependent cyclic nucleotide phosphodiesterase. A procedure for combined sequential affinity adsorption-electrophoresis has been devised. Its use for the rapid purification of a calcium-dependent cyclic nucleotide phosphodiesterase from bovine brain in high yield is described. In this procedure, proteins bound to a solid phase of calcium-dependent regulatory protein (CDR) linked to Sepharose 4B were electrophoretically eluted, concentrated, and separated, thus avoiding the large losses in activity incurred during attempts to purify further the phosphodiesterase eluted by conventional means. The highly purified phosphodiesterase prepared by this method was stable for months at -60 degrees C in the presence of glycerol. It has a higher affinity for cyclic GMP than for cyclic AMP, and hydrolysis of both substrates is stimulated 5- to 6-fold by calcium plus CDR. Factors that influence adsorption of the enzyme to CDR-Sepharose and selection of optimal conditions for electrophoresis were investigated. Sequential adsorption-electrophoresis should be generally useful in the purification of macromolecules for which affinity adsorbents are available. The procedures described here could be directly applicable to the purification of proteins that, like the phosphodiesterase, interact with CDR."}
{"id": "PMID:228271", "title": "Regulation of activity of chromatin receptors for thyroid hormone: possible involvement of histone-like proteins.", "content": "Thyroid hormone receptors lose their capability for high-affinity binding of the biologically active triiodothyronine after solubilization and separation from other chromatin proteins. The high-affinity triiodothyronine-binding capacity can be reconstituted by addition of a histone-containing extract of chromatin of purified core histones (H2A, H2B, H3, and H4); a number of other acidic or basic proteins tested were ineffective. The data support a model of the receptor in which a \"core\" receptor subunit that contains a thyroid hormone-binding site interacts with a regulatory subunit, which is possibly a histone or histone-like species. This interaction with the \"core\" subunit enables the resulting \"holo\" receptor to bind biologically active hormones. These data also suggest that histones or related proteins can modulate the activity of nonhistone chromosomal proteins that are involved in regulating the expression of specific genes.", "contents": "Regulation of activity of chromatin receptors for thyroid hormone: possible involvement of histone-like proteins. Thyroid hormone receptors lose their capability for high-affinity binding of the biologically active triiodothyronine after solubilization and separation from other chromatin proteins. The high-affinity triiodothyronine-binding capacity can be reconstituted by addition of a histone-containing extract of chromatin of purified core histones (H2A, H2B, H3, and H4); a number of other acidic or basic proteins tested were ineffective. The data support a model of the receptor in which a \"core\" receptor subunit that contains a thyroid hormone-binding site interacts with a regulatory subunit, which is possibly a histone or histone-like species. This interaction with the \"core\" subunit enables the resulting \"holo\" receptor to bind biologically active hormones. These data also suggest that histones or related proteins can modulate the activity of nonhistone chromosomal proteins that are involved in regulating the expression of specific genes."}
{"id": "PMID:228272", "title": "Squalene synthetase activity in human fibroblasts: regulation via the low density lipoprotein receptor.", "content": "Squalene synthetase (farnesyltransferase; farnesyl diphosphate:farnesyl-diphosphate farnesyltransferase, EC 2.5.1.21), the enzyme in the cholesterol biosynthetic pathway that converts farnesyl pyrophosphate into squalene, is subject to regulation in cultured human fibroblasts. When cholesterol-carrying low density lipoprotein (LDL) was removed from the serum of the culture medium, squalene synthetase activity increased 8-fold over 24 hr. When LDL was added back to the medium, squalene synthetase was slowly suppressed, 50% and 90% reduction occurring in 15 and 48 hr, respectively. Suppression of squalene synthetase required uptake of LDL via the LDL receptor; hence, it did not occur in mutant fibroblasts from a patient with homozygous familial hypercholesterolemia that lack receptors. The addition of a mixture of 25-hydroxycholesterol and cholesterol suppressed squalene synthetase equally well in normal and mutant fibroblasts. Coupled with previous data, the current findings indicate that cholesterol derived from LDL regulates at least two enzymes in the cholesterol synthetic pathway in fibroblasts: (i) its primary action is to rapidly suppress 3-hydroxy-3-methylglutaryl coenzyme A reductase [mevalonate:NADP(+), oxidoreductase (CoA-acylating), EC 1.1.1.34], which reduces mevalonate production by 95% within 8 hr, and (ii) its secondary action is to slowly suppress squalene synthetase. The LDL-mediated suppression of squalene synthetase does not regulate de novo cholesterol synthesis; it occurs after 3-hydroxy-3-methylglutaryl coenzyme A reductase is already suppressed. Rather, we hypothesize that it may function to allow the pool size of farnesyl pyrophosphate to be maintained in the presence of LDL so that low levels of mevalonate can be shunted preferentially into nonsterol products, such as ubiquinone-10 and dolichol. This mechanism may explain the earlier observation that the synthesis of ubiquinone-10 in fibroblasts proceeds at a normal rate in the presence of LDL despite a 95% decrease in mevalonate production.", "contents": "Squalene synthetase activity in human fibroblasts: regulation via the low density lipoprotein receptor. Squalene synthetase (farnesyltransferase; farnesyl diphosphate:farnesyl-diphosphate farnesyltransferase, EC 2.5.1.21), the enzyme in the cholesterol biosynthetic pathway that converts farnesyl pyrophosphate into squalene, is subject to regulation in cultured human fibroblasts. When cholesterol-carrying low density lipoprotein (LDL) was removed from the serum of the culture medium, squalene synthetase activity increased 8-fold over 24 hr. When LDL was added back to the medium, squalene synthetase was slowly suppressed, 50% and 90% reduction occurring in 15 and 48 hr, respectively. Suppression of squalene synthetase required uptake of LDL via the LDL receptor; hence, it did not occur in mutant fibroblasts from a patient with homozygous familial hypercholesterolemia that lack receptors. The addition of a mixture of 25-hydroxycholesterol and cholesterol suppressed squalene synthetase equally well in normal and mutant fibroblasts. Coupled with previous data, the current findings indicate that cholesterol derived from LDL regulates at least two enzymes in the cholesterol synthetic pathway in fibroblasts: (i) its primary action is to rapidly suppress 3-hydroxy-3-methylglutaryl coenzyme A reductase [mevalonate:NADP(+), oxidoreductase (CoA-acylating), EC 1.1.1.34], which reduces mevalonate production by 95% within 8 hr, and (ii) its secondary action is to slowly suppress squalene synthetase. The LDL-mediated suppression of squalene synthetase does not regulate de novo cholesterol synthesis; it occurs after 3-hydroxy-3-methylglutaryl coenzyme A reductase is already suppressed. Rather, we hypothesize that it may function to allow the pool size of farnesyl pyrophosphate to be maintained in the presence of LDL so that low levels of mevalonate can be shunted preferentially into nonsterol products, such as ubiquinone-10 and dolichol. This mechanism may explain the earlier observation that the synthesis of ubiquinone-10 in fibroblasts proceeds at a normal rate in the presence of LDL despite a 95% decrease in mevalonate production."}
{"id": "PMID:228273", "title": "Structure and specific sequences of avian erythroblastosis virus RNA: evidence for multiple classes of transforming genes among avian tumor viruses.", "content": "Two major RNA species were found in several clonal isolates of avian erythroblastosis virus (AEV) and avian erythroblastosis-associated helper virus (AEAV) complexes: one of 8.7 kilobases (kb), the other of 5.5 kb. The 5.5-kb species was identified as AEV RNA because (i) it was absent from non-transforming AEAV isolated from the same virus complex, (ii) it was present in complexes of AEV and different helper viruses, and (iii) its structure is similar to that of avian acute leukemia viruses of the MC29 group. Molecular hybridization indicated that 54% of AEV RNA is specific and 46% is related to other viruses of the avian tumor virus group, particularly to AEAV, therefore termed group-specific. The genetic structure of AEV RNA was deduced by mapping oligonucleotides representing specific and group-specific sequences and by comparing the resulting map to maps of AEAV and of other avian tumor viruses derived previously. AEV RNA contains a gag gene-related, 5' group-specific section of 1 kb, an internal AEV-specific section of 3 kb unrelated to any other viral RNA tested, and a 3' group-specific section of 1.5 kb. The 5' section of AEV RNA is closely related to analogous 5' sections of the MC29 group viruses and is homologous with a 5' RNA section that is part of the gag gene of AEAV. The 3' section is also shared with AEAV RNA and includes a variant C-oligonucleotide near the 3' end that is different from the highly conserved counterparts of all other exogenous avian tumor viruses. By analogy with Rous sarcoma virus and the acute leukemia viruses of the MC29 group, the internal specific section of AEV RNA is thought to signal a third class of onc genes in avian tumor viruses. Comparisons with AEAV and the MC29 group viruses suggest that both the 5' gag-related and the internal specific RNA sections of AEV are necessary for onc gene function.", "contents": "Structure and specific sequences of avian erythroblastosis virus RNA: evidence for multiple classes of transforming genes among avian tumor viruses. Two major RNA species were found in several clonal isolates of avian erythroblastosis virus (AEV) and avian erythroblastosis-associated helper virus (AEAV) complexes: one of 8.7 kilobases (kb), the other of 5.5 kb. The 5.5-kb species was identified as AEV RNA because (i) it was absent from non-transforming AEAV isolated from the same virus complex, (ii) it was present in complexes of AEV and different helper viruses, and (iii) its structure is similar to that of avian acute leukemia viruses of the MC29 group. Molecular hybridization indicated that 54% of AEV RNA is specific and 46% is related to other viruses of the avian tumor virus group, particularly to AEAV, therefore termed group-specific. The genetic structure of AEV RNA was deduced by mapping oligonucleotides representing specific and group-specific sequences and by comparing the resulting map to maps of AEAV and of other avian tumor viruses derived previously. AEV RNA contains a gag gene-related, 5' group-specific section of 1 kb, an internal AEV-specific section of 3 kb unrelated to any other viral RNA tested, and a 3' group-specific section of 1.5 kb. The 5' section of AEV RNA is closely related to analogous 5' sections of the MC29 group viruses and is homologous with a 5' RNA section that is part of the gag gene of AEAV. The 3' section is also shared with AEAV RNA and includes a variant C-oligonucleotide near the 3' end that is different from the highly conserved counterparts of all other exogenous avian tumor viruses. By analogy with Rous sarcoma virus and the acute leukemia viruses of the MC29 group, the internal specific section of AEV RNA is thought to signal a third class of onc genes in avian tumor viruses. Comparisons with AEAV and the MC29 group viruses suggest that both the 5' gag-related and the internal specific RNA sections of AEV are necessary for onc gene function."}
{"id": "PMID:228274", "title": "Characterization of the protein kinase activity of avian sarcoma virus src gene product.", "content": "The avian sarcoma virus src gene product, p60src, has been purified 650-fold from cytoplasmic extracts of the rat tumor cell line RR1022 by using ammonium sulfate fractionation, hydrophobic chromatography on omega-aminohexyl agarose, and ion exchange chromatography on phosphocellulose. Partially purified p60src is a monomer, with a native molecular weight of about 60,000 and an apparent pI of 6.0. In immunoprecipitates, p60src catalyzed phosphorylation of anti-p60src IgG heavy chains within the variable (VH) domain, which contains the heavy chain portion of the antigen combining site. Crude preparations of p60src contained phosphatase activity able to cleave phosphate from IgG heavy chains; this activity was removed by the purification procedure, and partially purified p60src could phosphorylate the heavy chain of specific antibody in solution. Furthermore, purified p60src catalyzed phosphorylation in solution of the general protein kinase substrate, alpha-casein, strengthening the hypothesis that it may in fact function as a protein kinase in vivo.", "contents": "Characterization of the protein kinase activity of avian sarcoma virus src gene product. The avian sarcoma virus src gene product, p60src, has been purified 650-fold from cytoplasmic extracts of the rat tumor cell line RR1022 by using ammonium sulfate fractionation, hydrophobic chromatography on omega-aminohexyl agarose, and ion exchange chromatography on phosphocellulose. Partially purified p60src is a monomer, with a native molecular weight of about 60,000 and an apparent pI of 6.0. In immunoprecipitates, p60src catalyzed phosphorylation of anti-p60src IgG heavy chains within the variable (VH) domain, which contains the heavy chain portion of the antigen combining site. Crude preparations of p60src contained phosphatase activity able to cleave phosphate from IgG heavy chains; this activity was removed by the purification procedure, and partially purified p60src could phosphorylate the heavy chain of specific antibody in solution. Furthermore, purified p60src catalyzed phosphorylation in solution of the general protein kinase substrate, alpha-casein, strengthening the hypothesis that it may in fact function as a protein kinase in vivo."}
{"id": "PMID:228275", "title": "A new endogenous primate type C virus isolated from the Old World monkey Colobus polykomos.", "content": "A new, genetically transmitted retrovirus has been isolated from the Old World monkey Colobus polykomos. This virus, designated CPC-1, is readily transmitted to both feline and human cells in culture. Nucleic acid hybridization studies reveal that there are 50-70 copies of the CPC-1 genome in colobus cellular DNA. Related virogene sequences can be detected in the DNA of all other Old World monkeys, as well as in the DNA of at least one ape species, the chimpanzee, indicating that this virus has been genetically transmitted in primates for 30-40 million years. CPC-1 is partially related to the type C virus previously isolated from stumptail monkeys (MAC-1). These two viruses have nucleic acid sequence homology, antigenic crossreactivity in their major viral structural protein, and a very similar host range in vitro. CPC-1 and MAC-1 therefore belong to the same class of genetically transmitted primate type C viruses and, as such, represent the first example in primates of analogous endogenous retroviruses isolated from two distantly related species.", "contents": "A new endogenous primate type C virus isolated from the Old World monkey Colobus polykomos. A new, genetically transmitted retrovirus has been isolated from the Old World monkey Colobus polykomos. This virus, designated CPC-1, is readily transmitted to both feline and human cells in culture. Nucleic acid hybridization studies reveal that there are 50-70 copies of the CPC-1 genome in colobus cellular DNA. Related virogene sequences can be detected in the DNA of all other Old World monkeys, as well as in the DNA of at least one ape species, the chimpanzee, indicating that this virus has been genetically transmitted in primates for 30-40 million years. CPC-1 is partially related to the type C virus previously isolated from stumptail monkeys (MAC-1). These two viruses have nucleic acid sequence homology, antigenic crossreactivity in their major viral structural protein, and a very similar host range in vitro. CPC-1 and MAC-1 therefore belong to the same class of genetically transmitted primate type C viruses and, as such, represent the first example in primates of analogous endogenous retroviruses isolated from two distantly related species."}
{"id": "PMID:228276", "title": "Cell-free synthesis and processing of a putative precursor for mitochondrial carbamyl phosphate synthetase I of rat liver.", "content": "Total RNA or poly(A)(+) RNA of rat liver was translated in a rabbit reticulocyte or wheat germ protein-synthesizing system and the carbamyl phosphate synthetase I [carbamoyl-phosphate synthetase (ammonia); carbon dioxide: ammonia ligase (ADP-forming, carbamate-phosphorylating), EC 6.3.4.16] synthesized was isolated by indirect immunoprecipitation by using antibody purified on enzyme-bound Sepharose and Staphylococcus aureus cells. The in vitro product moved on sodium dodecyl sulfate/polyacrylamide gels as a polypeptide that was about 5000 daltons larger than the subunit of the mature enzyme (160,000 daltons). The same polypeptide was also obtained by direct immunoprecipitation or by a double-antibody precipitation method. The mature enzyme competed effectively with the in vitro product for interaction with anti-carbamyl phosphate synthetase I antibody. Digestion of the in vitro product by S. aureus protease gave a pattern of peptide fragments similar to that of the mature enzyme. A mitochondrial membrane preparation from rat liver converted the in vitro product into a polypeptide that comigrated with the mature subunit on sodium dodecyl sulfate gel electrophoresis. Similar proteolytic activity was not detected in either a cytosol or a microsomal fraction of rat liver. These results indicate that the enzyme is synthesized as a larger precursor which is converted to the mature form of enzyme by posttranslational processing.", "contents": "Cell-free synthesis and processing of a putative precursor for mitochondrial carbamyl phosphate synthetase I of rat liver. Total RNA or poly(A)(+) RNA of rat liver was translated in a rabbit reticulocyte or wheat germ protein-synthesizing system and the carbamyl phosphate synthetase I [carbamoyl-phosphate synthetase (ammonia); carbon dioxide: ammonia ligase (ADP-forming, carbamate-phosphorylating), EC 6.3.4.16] synthesized was isolated by indirect immunoprecipitation by using antibody purified on enzyme-bound Sepharose and Staphylococcus aureus cells. The in vitro product moved on sodium dodecyl sulfate/polyacrylamide gels as a polypeptide that was about 5000 daltons larger than the subunit of the mature enzyme (160,000 daltons). The same polypeptide was also obtained by direct immunoprecipitation or by a double-antibody precipitation method. The mature enzyme competed effectively with the in vitro product for interaction with anti-carbamyl phosphate synthetase I antibody. Digestion of the in vitro product by S. aureus protease gave a pattern of peptide fragments similar to that of the mature enzyme. A mitochondrial membrane preparation from rat liver converted the in vitro product into a polypeptide that comigrated with the mature subunit on sodium dodecyl sulfate gel electrophoresis. Similar proteolytic activity was not detected in either a cytosol or a microsomal fraction of rat liver. These results indicate that the enzyme is synthesized as a larger precursor which is converted to the mature form of enzyme by posttranslational processing."}
{"id": "PMID:228277", "title": "Concomitant synthesis of beta-endorphin and alpha-melanotropin from two forms of pro-opiomelanocortin in the rat pars intermedia.", "content": "In the pars intermedia of rat pituitary glands, two forms of a common precursor for corticotropin (ACTH) and beta-lipotropin with apparent molecular weights of 34,000 and 36,000 were resolved by sodium dodecyl sulfate/acrylamide gradient slab gel electrophoresis. High-performance liquid chromatographic analysis of [35S]methionine-labeled tryptic fragments of the two forms of the precursor revealed that both contained copies of ACTH-(1-8) and beta-lipotropin-(61-69) sequences. When biosynthetic studies were performed in the presence of tunicamycin, the 34,000- and 36,000-dalton forms were replaced by a peptide with an apparent molecular weight of 32,000. It was therefore concluded that the 34,000- and 36,000-dalton forms of the precursor represent two glycoprotein variants of similar polypeptides, differing in the number of asparagine-linked carbohydrate moieties. During pulse-chase incubations with [35S]methionine, the precursor forms were cleaved into two major groups of labeled products: (i) beta-endorphin and (ii) a mixture of ACTH fragments closely related to alpha-melanotropin. No ACTH-(1-39) was found at the end of a 2-hr chase period, suggesting that ACTH is not a significant hormone product of the rat pars intermedia.", "contents": "Concomitant synthesis of beta-endorphin and alpha-melanotropin from two forms of pro-opiomelanocortin in the rat pars intermedia. In the pars intermedia of rat pituitary glands, two forms of a common precursor for corticotropin (ACTH) and beta-lipotropin with apparent molecular weights of 34,000 and 36,000 were resolved by sodium dodecyl sulfate/acrylamide gradient slab gel electrophoresis. High-performance liquid chromatographic analysis of [35S]methionine-labeled tryptic fragments of the two forms of the precursor revealed that both contained copies of ACTH-(1-8) and beta-lipotropin-(61-69) sequences. When biosynthetic studies were performed in the presence of tunicamycin, the 34,000- and 36,000-dalton forms were replaced by a peptide with an apparent molecular weight of 32,000. It was therefore concluded that the 34,000- and 36,000-dalton forms of the precursor represent two glycoprotein variants of similar polypeptides, differing in the number of asparagine-linked carbohydrate moieties. During pulse-chase incubations with [35S]methionine, the precursor forms were cleaved into two major groups of labeled products: (i) beta-endorphin and (ii) a mixture of ACTH fragments closely related to alpha-melanotropin. No ACTH-(1-39) was found at the end of a 2-hr chase period, suggesting that ACTH is not a significant hormone product of the rat pars intermedia."}
{"id": "PMID:228278", "title": "Interaction site of Escherichia coli cyclic AMP receptor protein on DNA of galactose operon promoters.", "content": "Cyclic AMP (cAMP) and its receptor protein (CRP) have a dual role in the regulation of the two promoters that control the galactose (gal) operon of Escherichia coli. One promoter, P1, requires cAMP-CRP for activity; the other, P2, is inhibited by these factors. We have examined the interactions site of cAMP-CRP on gal DNA by using two types of protection experiments, involving DNase digestion and methylation by dimethyl sulfate. Our results indicate that cAMP-CRP binds to gal DNA in a segment located between 50 and 24 base pairs preceding the P1 start point for transcription. Although the location of the cAMP-CRP interaction site is clearly different in gal and lac DNA, comparison of the DNA sequences suggests a similar recognition sequence. The location of the cAMP . CRP-binding site in gal further suggests that protein-protein interactions between RNA polymerase and cAMP . CRP play an important role in transcription initiation at the gal and possibly other cAMP-dependent promoters.", "contents": "Interaction site of Escherichia coli cyclic AMP receptor protein on DNA of galactose operon promoters. Cyclic AMP (cAMP) and its receptor protein (CRP) have a dual role in the regulation of the two promoters that control the galactose (gal) operon of Escherichia coli. One promoter, P1, requires cAMP-CRP for activity; the other, P2, is inhibited by these factors. We have examined the interactions site of cAMP-CRP on gal DNA by using two types of protection experiments, involving DNase digestion and methylation by dimethyl sulfate. Our results indicate that cAMP-CRP binds to gal DNA in a segment located between 50 and 24 base pairs preceding the P1 start point for transcription. Although the location of the cAMP-CRP interaction site is clearly different in gal and lac DNA, comparison of the DNA sequences suggests a similar recognition sequence. The location of the cAMP . CRP-binding site in gal further suggests that protein-protein interactions between RNA polymerase and cAMP . CRP play an important role in transcription initiation at the gal and possibly other cAMP-dependent promoters."}
{"id": "PMID:228279", "title": "Beta-turns in nascent procollagen are sites of posttranslational enzymatic hydroxylation of proline.", "content": "The selective hydroxylation of proline residues in nascent procollagen chains by prolyl hydroxylase (EC 1.14.11.2) can be understood in terms of the conformational feature of the -Pro-Gly-segments in linear peptides and globular proteins. The folded beta-turn conformation in such segments appears to be the conformational requirement for proline hydroxylation. The available data on the hydroxylation of native and synthetic substrates of prolyl hydroxylase are explained on the basis of the extent of beta-turn formation in them. Taken in conjunction with the conformational features of the hydroxyproline residue, our results bring out the conformational reason for the posttranslational proline hydroxylation which, it is proposed, leads to the \"straightening\" of the beta-turn segments into the linear triple-helical conformation.", "contents": "Beta-turns in nascent procollagen are sites of posttranslational enzymatic hydroxylation of proline. The selective hydroxylation of proline residues in nascent procollagen chains by prolyl hydroxylase (EC 1.14.11.2) can be understood in terms of the conformational feature of the -Pro-Gly-segments in linear peptides and globular proteins. The folded beta-turn conformation in such segments appears to be the conformational requirement for proline hydroxylation. The available data on the hydroxylation of native and synthetic substrates of prolyl hydroxylase are explained on the basis of the extent of beta-turn formation in them. Taken in conjunction with the conformational features of the hydroxyproline residue, our results bring out the conformational reason for the posttranslational proline hydroxylation which, it is proposed, leads to the \"straightening\" of the beta-turn segments into the linear triple-helical conformation."}
{"id": "PMID:228280", "title": "Triplet states in photosystem I of spinach chloroplasts and subchloroplast particles.", "content": "We report light-induced electron paramagnetic resonance triplet spectra from samples of chloroplasts or digitonin photosystem I particles that depend upon the dark redox state of the bound acceptors of photosystem I. If the reaction centers are prepared in the redox state P-700 A X- FdB-FdA-, then upon illumination at 11K we observe a polarized chlorophyll triplet species which we interpret as arising from radical pair recombination between P-700+ and A-. This chlorophyll triplet is apparently the analog of the PR state of photosynthetic bacteria [Parson, W.W. & Cogdell, R.J. (1975) Biochim. Biophys. Acta 416, 105-149]. If the reaction centers are prepared in the dark redox state P-700 A X FdB-FdA-, then upon illumination at 11K we observe a different triplet species of uncertain origin, possibly pheophytin or carotenoid. This species is closely associated with the photosystem I reaction center and it traps excitation when P-700 is oxidized.", "contents": "Triplet states in photosystem I of spinach chloroplasts and subchloroplast particles. We report light-induced electron paramagnetic resonance triplet spectra from samples of chloroplasts or digitonin photosystem I particles that depend upon the dark redox state of the bound acceptors of photosystem I. If the reaction centers are prepared in the redox state P-700 A X- FdB-FdA-, then upon illumination at 11K we observe a polarized chlorophyll triplet species which we interpret as arising from radical pair recombination between P-700+ and A-. This chlorophyll triplet is apparently the analog of the PR state of photosynthetic bacteria [Parson, W.W. & Cogdell, R.J. (1975) Biochim. Biophys. Acta 416, 105-149]. If the reaction centers are prepared in the dark redox state P-700 A X FdB-FdA-, then upon illumination at 11K we observe a different triplet species of uncertain origin, possibly pheophytin or carotenoid. This species is closely associated with the photosystem I reaction center and it traps excitation when P-700 is oxidized."}
{"id": "PMID:228281", "title": "Adrenocorticotropin (ACTH) induces phosphorylation of a cytoplasmic protein in intact isolated adrenocortical cells.", "content": "In 32P incorporation experiments with intact adrenocortical cells, adrenocorticotropin (ACTH) or adenosine 3',5'-cyclic monophosphate (cAMP) induced a rapid and transient increase of approximately 300-500% in the phosphorylation of a 32P-containing cytoplasmic protein of about 150,000 daltons (APS150). Half-maximal stimulation of APS150 phosphorylation was observed with about 3 pM ACTH. Receptor-bound cAMP, corticosterone production, and the appearance of phosphorylated APS150 increased in parallel with respect to both time and ACTH concentration. All three responses were dependent on extracellular calcium. Inhibition of protein synthesis with cycloheximide suggested a half-life of APS150 of about 10 min. The time course of 32P incorporation into ACTH-induced APS150 in the absence and presence of nonradioactive phosphate shows that the phosphorylation of APS150 is under simultaneous control of cAMP-dependent protein kinase and of phosphoatase activity. Thus a rapid ACTH-dependent and cAMP-dependent protein phosphorylation in intact adrenocortical cells within steroidogenic ACTH concentrations has now been demonstrated.", "contents": "Adrenocorticotropin (ACTH) induces phosphorylation of a cytoplasmic protein in intact isolated adrenocortical cells. In 32P incorporation experiments with intact adrenocortical cells, adrenocorticotropin (ACTH) or adenosine 3',5'-cyclic monophosphate (cAMP) induced a rapid and transient increase of approximately 300-500% in the phosphorylation of a 32P-containing cytoplasmic protein of about 150,000 daltons (APS150). Half-maximal stimulation of APS150 phosphorylation was observed with about 3 pM ACTH. Receptor-bound cAMP, corticosterone production, and the appearance of phosphorylated APS150 increased in parallel with respect to both time and ACTH concentration. All three responses were dependent on extracellular calcium. Inhibition of protein synthesis with cycloheximide suggested a half-life of APS150 of about 10 min. The time course of 32P incorporation into ACTH-induced APS150 in the absence and presence of nonradioactive phosphate shows that the phosphorylation of APS150 is under simultaneous control of cAMP-dependent protein kinase and of phosphoatase activity. Thus a rapid ACTH-dependent and cAMP-dependent protein phosphorylation in intact adrenocortical cells within steroidogenic ACTH concentrations has now been demonstrated."}
{"id": "PMID:228282", "title": "Transformation by Rous sarcoma virus: effects of src gene expression on the synthesis and phosphorylation of cellular polypeptides.", "content": "Infection of chicken embryo fibroblasts by Rous sarcoma virus induces a variety of alterations in cellular growth and morphology. We have used two-dimensional polyacrylamide gel electrophoresis to examine the effects of viral transformation on the pattern of synthesis and phosphorylation of cellular polypeptides. Infection by Rous sarcoma virus does not appear to induce the de novo synthesis, or the complete suppression, of any of the [35S]methionine-labeled cellular polypeptides that can be resolved with this technique; however, there are quantitative changes in a minor fraction (approximately 4%) of the [35S]methionine-labeled polypeptides. When cells labeled with [32P]orthophosphate were examined, a phosphorylated polypeptide, Mr 36,000, was detected in transformed cells; this polypeptide appears within 20 min when cells infected by a temperature-sensitive mutant of Rous sarcoma virus are shifted from the nonpermissive to the permissive temperature. Phosphorylation of the 36,000 Mr polypeptide thus represents an early event in the process of transformation, and it is possible that this polypeptide is a target for the kinase activity associated with pp60src.", "contents": "Transformation by Rous sarcoma virus: effects of src gene expression on the synthesis and phosphorylation of cellular polypeptides. Infection of chicken embryo fibroblasts by Rous sarcoma virus induces a variety of alterations in cellular growth and morphology. We have used two-dimensional polyacrylamide gel electrophoresis to examine the effects of viral transformation on the pattern of synthesis and phosphorylation of cellular polypeptides. Infection by Rous sarcoma virus does not appear to induce the de novo synthesis, or the complete suppression, of any of the [35S]methionine-labeled cellular polypeptides that can be resolved with this technique; however, there are quantitative changes in a minor fraction (approximately 4%) of the [35S]methionine-labeled polypeptides. When cells labeled with [32P]orthophosphate were examined, a phosphorylated polypeptide, Mr 36,000, was detected in transformed cells; this polypeptide appears within 20 min when cells infected by a temperature-sensitive mutant of Rous sarcoma virus are shifted from the nonpermissive to the permissive temperature. Phosphorylation of the 36,000 Mr polypeptide thus represents an early event in the process of transformation, and it is possible that this polypeptide is a target for the kinase activity associated with pp60src."}
{"id": "PMID:228283", "title": "Autoimmune and lymphoproliferative disease in (B6-GIX+ X 129)F1 mice: relation to naturally occurring  antibodies against murine leukemia virus-related cell surface antigens.", "content": "G(IX) congeneic mouse strains, C57BL/6-G(IX) (+)(B6-G(IX) (+)) and 129-G(IX) (-), have been derived from the prototype strains, B6(G(IX) (-)) and 129(G(IX) (+)). The hybrids, (B6-G(IX) (+) x 129)F(1) (G(IX) (+)F(1)) and (B6 x 129-G(IX) (-))F(1) (G(IX) (-)F(1)), differ only in regard to genetic loci controlling G(IX) antigen expression. G(IX) (+)F(1) mice spontaneously produce G(IX) antibody and often show signs of autoimmune disease and lymphoproliferative disease. G(IX) (-)F(1) mice and mice of the two parental strains (B6-G(IX) (+) and 129) of G(IX) (+)F(1) do not produce G(IX) antibody and seldom show signs of these diseases. G((ERLD)), and G((RADA1)), antibodies, natural thymocytotoxic autoantibody, and antinuclear antibodies were produced by G(IX) (+)F(1) mice. However, these four antibodies were also found in the other strains. G(IX) (+)F(1) mice develop pronounced diffuse glomerulonephritis similar to that found in systemic lupus erythematosus in man. Incidence studies in which mice were examined according to age rather than state of health showed that the lesions occurred in 38% of G(IX) (+)F(1) mice but not in G(IX) (-)F(1), B6-G(IX) (+), or 129 mice. Lymphoproliferative lesions were either reticulum cell sarcoma (RCS) type A or reactive lymphoid hyperplasia (RLH). RCS occurred more often in G(IX) (+)F(1) (38%) than in G(IX) (-)F(1) (12%) or B6-G(IX) (+) (8%). No RCS occurred in mice of the 129 strain. RLH occurred in G(IX) (+)F(1) mice (10%) but not in the other strains. From these results, the following conclusions are drawn: (i) Severe glomerulonephritis and the increased occurrence of lymphoproliferative lesions in these animals depend on the presence of G(IX) antigen; (ii) besides genes controlling G(IX) antigen expression, other genes from both parental strains are required to create the basis in the progeny F(1) mice for the development of these diseases; and (iii) the chronic production of G(IX) antibody may be necessary for the development of the severe glomerulonephritis and for the increased occurrence of lymphoproliferative diseases in G(IX) (+)F(1) mice.", "contents": "Autoimmune and lymphoproliferative disease in (B6-GIX+ X 129)F1 mice: relation to naturally occurring  antibodies against murine leukemia virus-related cell surface antigens. G(IX) congeneic mouse strains, C57BL/6-G(IX) (+)(B6-G(IX) (+)) and 129-G(IX) (-), have been derived from the prototype strains, B6(G(IX) (-)) and 129(G(IX) (+)). The hybrids, (B6-G(IX) (+) x 129)F(1) (G(IX) (+)F(1)) and (B6 x 129-G(IX) (-))F(1) (G(IX) (-)F(1)), differ only in regard to genetic loci controlling G(IX) antigen expression. G(IX) (+)F(1) mice spontaneously produce G(IX) antibody and often show signs of autoimmune disease and lymphoproliferative disease. G(IX) (-)F(1) mice and mice of the two parental strains (B6-G(IX) (+) and 129) of G(IX) (+)F(1) do not produce G(IX) antibody and seldom show signs of these diseases. G((ERLD)), and G((RADA1)), antibodies, natural thymocytotoxic autoantibody, and antinuclear antibodies were produced by G(IX) (+)F(1) mice. However, these four antibodies were also found in the other strains. G(IX) (+)F(1) mice develop pronounced diffuse glomerulonephritis similar to that found in systemic lupus erythematosus in man. Incidence studies in which mice were examined according to age rather than state of health showed that the lesions occurred in 38% of G(IX) (+)F(1) mice but not in G(IX) (-)F(1), B6-G(IX) (+), or 129 mice. Lymphoproliferative lesions were either reticulum cell sarcoma (RCS) type A or reactive lymphoid hyperplasia (RLH). RCS occurred more often in G(IX) (+)F(1) (38%) than in G(IX) (-)F(1) (12%) or B6-G(IX) (+) (8%). No RCS occurred in mice of the 129 strain. RLH occurred in G(IX) (+)F(1) mice (10%) but not in the other strains. From these results, the following conclusions are drawn: (i) Severe glomerulonephritis and the increased occurrence of lymphoproliferative lesions in these animals depend on the presence of G(IX) antigen; (ii) besides genes controlling G(IX) antigen expression, other genes from both parental strains are required to create the basis in the progeny F(1) mice for the development of these diseases; and (iii) the chronic production of G(IX) antibody may be necessary for the development of the severe glomerulonephritis and for the increased occurrence of lymphoproliferative diseases in G(IX) (+)F(1) mice."}
{"id": "PMID:228284", "title": "Enzyme therapy in Fabry disease: differential in vivo plasma clearance and metabolic effectiveness of plasma and splenic alpha-galactosidase A isozymes.", "content": "A pilot trial of enzyme replacement with splenic and plasma alpha-galactosidase A (alpha-D-galactosidase; alpha-D-galactoside galactohydrolase, EC 3.2.1.22) isozymes was undertaken in two brothers with Fabry disease, an X-linked glycosphingolipid storage disease. Six unentrapped doses (2000 units/kg) of each isozyme were administered intravenously to the respective recipients during a 117-day period. The circulating half-life of the splenic isozyme was about 10 min, whereas that for the plasma isozyme was approximately 70 min. No immune response was detected by skin and immunodiffusion tests or by alterations in the maximal activity or clearance kinetics for either isozyme after successive administrations. After each dose of the splenic isozyme, the concentration of the accumulated circulating substrate, trihexosylceramide (globotriaosylceramide), decreased maximally (approximately 50% of initial values) in 15 min and returned to preinfusion levels by 2-3 hr. In marked contrast, injection of the plasma isozyme decreased the circulating substrate levels 50-70% by 2-6 hr; the concentrations gradually returned to preinfusion values by 36-72 hr.", "contents": "Enzyme therapy in Fabry disease: differential in vivo plasma clearance and metabolic effectiveness of plasma and splenic alpha-galactosidase A isozymes. A pilot trial of enzyme replacement with splenic and plasma alpha-galactosidase A (alpha-D-galactosidase; alpha-D-galactoside galactohydrolase, EC 3.2.1.22) isozymes was undertaken in two brothers with Fabry disease, an X-linked glycosphingolipid storage disease. Six unentrapped doses (2000 units/kg) of each isozyme were administered intravenously to the respective recipients during a 117-day period. The circulating half-life of the splenic isozyme was about 10 min, whereas that for the plasma isozyme was approximately 70 min. No immune response was detected by skin and immunodiffusion tests or by alterations in the maximal activity or clearance kinetics for either isozyme after successive administrations. After each dose of the splenic isozyme, the concentration of the accumulated circulating substrate, trihexosylceramide (globotriaosylceramide), decreased maximally (approximately 50% of initial values) in 15 min and returned to preinfusion levels by 2-3 hr. In marked contrast, injection of the plasma isozyme decreased the circulating substrate levels 50-70% by 2-6 hr; the concentrations gradually returned to preinfusion values by 36-72 hr."}
{"id": "PMID:228285", "title": "Ultrasensitive enzymatic radioimmunoassay: application to detection of cholera toxin and rotavirus.", "content": "Rotavirus and enterotoxin-producing bacteria are major causes of diarrheal disease in humans. A method of rapid diagnosis, ultrasensitive enzymatic radioimmunoassay, has been developed to quantitatively detect cholera toxin and rotavirus. The method uses features of both enzyme-linked immunosorbent assay and radioimmunoassay; however, the sensitivity of the assay is 100- to 1000-fold more sensitive than the two parent assays. Ultrasensitive enzymatic radioimmunoassay should also be useful in measuring other biologically important agents such as drugs and hormones.", "contents": "Ultrasensitive enzymatic radioimmunoassay: application to detection of cholera toxin and rotavirus. Rotavirus and enterotoxin-producing bacteria are major causes of diarrheal disease in humans. A method of rapid diagnosis, ultrasensitive enzymatic radioimmunoassay, has been developed to quantitatively detect cholera toxin and rotavirus. The method uses features of both enzyme-linked immunosorbent assay and radioimmunoassay; however, the sensitivity of the assay is 100- to 1000-fold more sensitive than the two parent assays. Ultrasensitive enzymatic radioimmunoassay should also be useful in measuring other biologically important agents such as drugs and hormones."}
{"id": "PMID:228286", "title": "Tissue sites of degradation of low density lipoprotein: application of a method for determining the fate of plasma proteins.", "content": "A method for determining tissue sites of plasma protein degradation is described as applied to studies of low density lipoprotein (LDL) catabolism in swine. The method is based on the fact that sucrose is not degraded by lysosomal enzymes and thus accumulates in lysosomes. [(14)C]Sucrose was activated with cyanuric chloride and covalently coupled to the LDL protein. Studies in cultured fibroblasts have established that the sucrose (14)C accumulates intracellularly in degradation products at a rate equal to the rate of degradation of (125)I-labeled LDL simultaneously measured. In vivo the fractional catabolic rate of [(14)C]sucrose-LDL was the same as that of (125)I-labeled LDL. (14)C-Labeled degradation products in all major tissues were determined 24 hours after injection of [(14)C]sucrose-LDL. About 75% of the LDL degraded (calculated from analysis of the plasma decay curve) was accounted for in the (14)C-labeled degradation products accumulated in the tissues examined; only 4% appeared in the urine. In three studies, 37.9, 39.6, and 37.8% of the LDL degraded was recovered in the liver. Results were similar at 48 hr (38.7 and 39.9% hepatic degradation), but urinary losses were then about 10% and about 4% was lost in bile. All extrahepatic tissues examined contained (14)C-labeled degradation products. The concentration was highest in the adrenal glands-2 to 5 times that in liver and 10 times that in the next most active tissues. In principle this approach should be applicable to studies of the tissue sites of degradation of any of the plasma proteins.", "contents": "Tissue sites of degradation of low density lipoprotein: application of a method for determining the fate of plasma proteins. A method for determining tissue sites of plasma protein degradation is described as applied to studies of low density lipoprotein (LDL) catabolism in swine. The method is based on the fact that sucrose is not degraded by lysosomal enzymes and thus accumulates in lysosomes. [(14)C]Sucrose was activated with cyanuric chloride and covalently coupled to the LDL protein. Studies in cultured fibroblasts have established that the sucrose (14)C accumulates intracellularly in degradation products at a rate equal to the rate of degradation of (125)I-labeled LDL simultaneously measured. In vivo the fractional catabolic rate of [(14)C]sucrose-LDL was the same as that of (125)I-labeled LDL. (14)C-Labeled degradation products in all major tissues were determined 24 hours after injection of [(14)C]sucrose-LDL. About 75% of the LDL degraded (calculated from analysis of the plasma decay curve) was accounted for in the (14)C-labeled degradation products accumulated in the tissues examined; only 4% appeared in the urine. In three studies, 37.9, 39.6, and 37.8% of the LDL degraded was recovered in the liver. Results were similar at 48 hr (38.7 and 39.9% hepatic degradation), but urinary losses were then about 10% and about 4% was lost in bile. All extrahepatic tissues examined contained (14)C-labeled degradation products. The concentration was highest in the adrenal glands-2 to 5 times that in liver and 10 times that in the next most active tissues. In principle this approach should be applicable to studies of the tissue sites of degradation of any of the plasma proteins."}
{"id": "PMID:228287", "title": "Abelson antigen is expressed on hematopoietic spleen colony-forming cells from mice carrying the Av-2S virus sensitivity gene.", "content": "Abelson antigen is a cell-surface determinant specifically induced by the Abelson murine leukemia virus (A-MuLV); this antigen is also expressed on uninfected bone marrow of BALB/c mice. Antisera that contained antibody to Abelson antigen were cytotoxic for the spleen colony-forming cells (CFU-S) of adult bone marrow from BALB/c mice. Absorption tests with appropriate tissues and direct cytotoxic tests with bone marrow CFU-S from several mouse strains confirmed that the sensitivity of BALB/c CFU-S to lysis by anti-Abelson-antigen antisera was due to expression of Abelson antigen. Spleen or bone marrow from BALB/c mice undergoing hematopoietic regeneration amplified Abelson antigen expression, although no expression of Abelson antigen was observed on regenerating C57BL/B6 bone marrow or spleen. The presence of Abelson antigen on bone marrow cells of seven recombinant inbred strains coincided with the inheritance of sensitivity alleles at the Av-2 locus, a gene that determines susceptibility to A-MuLV lymphoma induction. These results indicate that expression of Ableson antigen may have a physiologic function in hematopoietic differentiation and a pathologic role in A-MuLV lymphomagenesis.", "contents": "Abelson antigen is expressed on hematopoietic spleen colony-forming cells from mice carrying the Av-2S virus sensitivity gene. Abelson antigen is a cell-surface determinant specifically induced by the Abelson murine leukemia virus (A-MuLV); this antigen is also expressed on uninfected bone marrow of BALB/c mice. Antisera that contained antibody to Abelson antigen were cytotoxic for the spleen colony-forming cells (CFU-S) of adult bone marrow from BALB/c mice. Absorption tests with appropriate tissues and direct cytotoxic tests with bone marrow CFU-S from several mouse strains confirmed that the sensitivity of BALB/c CFU-S to lysis by anti-Abelson-antigen antisera was due to expression of Abelson antigen. Spleen or bone marrow from BALB/c mice undergoing hematopoietic regeneration amplified Abelson antigen expression, although no expression of Abelson antigen was observed on regenerating C57BL/B6 bone marrow or spleen. The presence of Abelson antigen on bone marrow cells of seven recombinant inbred strains coincided with the inheritance of sensitivity alleles at the Av-2 locus, a gene that determines susceptibility to A-MuLV lymphoma induction. These results indicate that expression of Ableson antigen may have a physiologic function in hematopoietic differentiation and a pathologic role in A-MuLV lymphomagenesis."}
{"id": "PMID:228288", "title": "Guanine nucleotide-binding activity as an assay for src protein of rat-derived murine sarcoma viruses.", "content": "We have recently identified a 21,000-dalton protein, p21, coded for by Kirsten or Harvey murine sarcoma virus. On the basis of the results obtained with the p21 of a mutant of Kirsten sarcoma virus, temperature sensitive for the maintenance of transformation, we concluded that the p21 was required for the maintenance of transformation induced by either virus. We report herein that when extracts from cells transformed by Kirsten or Harvey sarcoma virus are incubated with [(3)H]GDP or [alpha-(32)P]GTP, picomole quantities of guanine nucleotide can be immunoprecipitated with antisera that contain antibodies to the p21. Previously we have shown that the immunoprecipitability of [(35)S]methionine-labeled p21 of the temperature-sensitive mutant of Kirsten sarcoma virus is thermolabile. The binding of guanine nucleotide is shown herein also to be thermolabile in extracts of cells transformed by the same mutant. However, the immunoprecipitability of the [(35)S]methionine-labeled p21 in such extracts of the temperature-sensitive mutant can be preserved if the extracts containing labeled p21 are incubated with added GDP or GTP prior to heating. The results suggest an interaction between p21 and certain guanine nucleotides, and the possible roles of guanine nucleotides and p21 in the maintenance of transformation are discussed.", "contents": "Guanine nucleotide-binding activity as an assay for src protein of rat-derived murine sarcoma viruses. We have recently identified a 21,000-dalton protein, p21, coded for by Kirsten or Harvey murine sarcoma virus. On the basis of the results obtained with the p21 of a mutant of Kirsten sarcoma virus, temperature sensitive for the maintenance of transformation, we concluded that the p21 was required for the maintenance of transformation induced by either virus. We report herein that when extracts from cells transformed by Kirsten or Harvey sarcoma virus are incubated with [(3)H]GDP or [alpha-(32)P]GTP, picomole quantities of guanine nucleotide can be immunoprecipitated with antisera that contain antibodies to the p21. Previously we have shown that the immunoprecipitability of [(35)S]methionine-labeled p21 of the temperature-sensitive mutant of Kirsten sarcoma virus is thermolabile. The binding of guanine nucleotide is shown herein also to be thermolabile in extracts of cells transformed by the same mutant. However, the immunoprecipitability of the [(35)S]methionine-labeled p21 in such extracts of the temperature-sensitive mutant can be preserved if the extracts containing labeled p21 are incubated with added GDP or GTP prior to heating. The results suggest an interaction between p21 and certain guanine nucleotides, and the possible roles of guanine nucleotides and p21 in the maintenance of transformation are discussed."}
{"id": "PMID:228289", "title": "Mouse mammary tumor virus genome expression in chemical carcinogen-induced mammary tumors in low- and high-tumor-incidence mouse strains.", "content": "Involvement of mouse mammary tumor virus (MMTV) in 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumorigenesis was investigated in low- (BALB/c) and high- (BALB/cfC3H) mammary-tumor-incidence mouse strains. Both strains contain endogenous MMTV integrated into the cellular genome. Additionally, BALB/cfC3H mice are infected with exogenous MMTV-S which is responsible for a higher incidence of mammary tumors in breeding females. Administration of DMBA to virgin mice of both strains resulted in a moderate frequency of mammary tumors within 40 wk after treatment. No differences were found in DMBA-induced tumor incidences at 18 wk (6% and 7%) or at 38 wk (29% and 36%) after treatment of BALB/c and BALB/cfC3H mice, respectively. Expression of MMTV in these tumors was examined by assaying for the presence of MMTV RNA by hybridization using MMTV-specific cDNA and by immunohistochemical staining utilizing antibodies against MMTV 52,000-dalton glycoprotein, gp52, and 28,000-dalton internal protein, p28. Of 16 BALB/c tumors assayed, 11 did not contain detectable levels of MMTV RNA and the remaining 5 tumors contained only low levels (0.0005-0.0010%) of viral RNA. Importantly, MMTV RNA was not detected in 5 of 27 BALB/cfC3H tumors. The other BALB/cfC3H tumors contained quantities of MMTV RNA ranging from 0.0006 to 0.4170%. Most BALB/cfC3H tumors with detectable levels of MMTV RNA also synthesized viral proteins gp52 and p28. Thus, expression of the complete MMTV genome is not requisite for maintenance of the tumor phenotype in DMBA-induced mammary tumors in either BALB/c or BALB/cfC3H virgin mice under 1 year of age.", "contents": "Mouse mammary tumor virus genome expression in chemical carcinogen-induced mammary tumors in low- and high-tumor-incidence mouse strains. Involvement of mouse mammary tumor virus (MMTV) in 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumorigenesis was investigated in low- (BALB/c) and high- (BALB/cfC3H) mammary-tumor-incidence mouse strains. Both strains contain endogenous MMTV integrated into the cellular genome. Additionally, BALB/cfC3H mice are infected with exogenous MMTV-S which is responsible for a higher incidence of mammary tumors in breeding females. Administration of DMBA to virgin mice of both strains resulted in a moderate frequency of mammary tumors within 40 wk after treatment. No differences were found in DMBA-induced tumor incidences at 18 wk (6% and 7%) or at 38 wk (29% and 36%) after treatment of BALB/c and BALB/cfC3H mice, respectively. Expression of MMTV in these tumors was examined by assaying for the presence of MMTV RNA by hybridization using MMTV-specific cDNA and by immunohistochemical staining utilizing antibodies against MMTV 52,000-dalton glycoprotein, gp52, and 28,000-dalton internal protein, p28. Of 16 BALB/c tumors assayed, 11 did not contain detectable levels of MMTV RNA and the remaining 5 tumors contained only low levels (0.0005-0.0010%) of viral RNA. Importantly, MMTV RNA was not detected in 5 of 27 BALB/cfC3H tumors. The other BALB/cfC3H tumors contained quantities of MMTV RNA ranging from 0.0006 to 0.4170%. Most BALB/cfC3H tumors with detectable levels of MMTV RNA also synthesized viral proteins gp52 and p28. Thus, expression of the complete MMTV genome is not requisite for maintenance of the tumor phenotype in DMBA-induced mammary tumors in either BALB/c or BALB/cfC3H virgin mice under 1 year of age."}
{"id": "PMID:228290", "title": "Multiple phosphorylation sites in protein I and their differential regulation by cyclic AMP and calcium.", "content": "The phosphorylation of protein I, a specific neuronal protein, has been found to be regulated both by cyclic AMP (cAMP) and by calcium, in intact as well as in lysed synaptosome preparations from rat brain. In order to determine the phosphorylation site(s) of protein I that were regulated by cAMP and calcium, protein I was purified after it was phosphorylated under various conditions. This purified protein I was then subjected either to peptide mapping after limited proteolysis in sodium dodecyl sulfate/polyacrylamide gels or to tryptic fingerprinting. 8-Br-cAMP selectively increased the phosphorylation of the same protein I peptide fragment in both intact and lysed synaptosomes. Depolarization-induced calcium influx into intact  synaptosomes, or the addition of calcium to lysed synaptosomes, caused a stimulation of the phosphorylation not only of this peptide but also of other distinct peptides. Differential regulation by cAMP and calcium of the phosphorylation of multiple sites on the same neuronal protein may provide a molecular basis for interactions between these two second-messenger systems in certain nerve terminal functions.", "contents": "Multiple phosphorylation sites in protein I and their differential regulation by cyclic AMP and calcium. The phosphorylation of protein I, a specific neuronal protein, has been found to be regulated both by cyclic AMP (cAMP) and by calcium, in intact as well as in lysed synaptosome preparations from rat brain. In order to determine the phosphorylation site(s) of protein I that were regulated by cAMP and calcium, protein I was purified after it was phosphorylated under various conditions. This purified protein I was then subjected either to peptide mapping after limited proteolysis in sodium dodecyl sulfate/polyacrylamide gels or to tryptic fingerprinting. 8-Br-cAMP selectively increased the phosphorylation of the same protein I peptide fragment in both intact and lysed synaptosomes. Depolarization-induced calcium influx into intact  synaptosomes, or the addition of calcium to lysed synaptosomes, caused a stimulation of the phosphorylation not only of this peptide but also of other distinct peptides. Differential regulation by cAMP and calcium of the phosphorylation of multiple sites on the same neuronal protein may provide a molecular basis for interactions between these two second-messenger systems in certain nerve terminal functions."}
{"id": "PMID:228291", "title": "Photoaffinity labeling of cyclic-AMP- and AMP-binding proteins differentiating Dictyostelium discoideum cells.", "content": "Cyclic-AMP-binding proteins play important roles during the differentiation of the cellular slime mold Dictyostelium discoideum. The photoaffinity reagent 8-N3-cyclic [32P]AMP has been used to label developmentally regulated cyclic-AMP-binding proteins of intact cells, membranes, and cytoplasm. 8-N3-Cyclic AMP is a chemoattractant for differentiated D. discoideum cells and is a substrate for the membrane phosphodiesterase (mPDE). When mPDE is inhibited, the only specifically labeled protein on intact cells has a molecular weight of 40,000 on sodium dodecyl sulfate gels. The developmental time course of appearance of this protein and its high specificity for cyclic AMP identify it as the cell surface chemotactic receptor for cyclic AMP. The concentration dependence of labeling of this protein is consistent with the measured chemotactic potency of 8-N3-cyclic AMP, which is about 1/100th that of cyclic AMP. Three developmentally regulated proteins (Mr 26,000, 33,000, and 36,000) of the soluble fraction (cytoplasm) are labeled by the photoaffinity reagent and are specific for cyclic AMP. By analogy with other systems, these may be regulatory subunits of protein kinases. The mPDE of ghosts or plasma membrane fractions converts the reagent to 8-N3-[32P]AMP, which specifically photoaffinity labels a protein of Mr 42,000 associated with the cytoplasmic face of the plasma membrane.", "contents": "Photoaffinity labeling of cyclic-AMP- and AMP-binding proteins differentiating Dictyostelium discoideum cells. Cyclic-AMP-binding proteins play important roles during the differentiation of the cellular slime mold Dictyostelium discoideum. The photoaffinity reagent 8-N3-cyclic [32P]AMP has been used to label developmentally regulated cyclic-AMP-binding proteins of intact cells, membranes, and cytoplasm. 8-N3-Cyclic AMP is a chemoattractant for differentiated D. discoideum cells and is a substrate for the membrane phosphodiesterase (mPDE). When mPDE is inhibited, the only specifically labeled protein on intact cells has a molecular weight of 40,000 on sodium dodecyl sulfate gels. The developmental time course of appearance of this protein and its high specificity for cyclic AMP identify it as the cell surface chemotactic receptor for cyclic AMP. The concentration dependence of labeling of this protein is consistent with the measured chemotactic potency of 8-N3-cyclic AMP, which is about 1/100th that of cyclic AMP. Three developmentally regulated proteins (Mr 26,000, 33,000, and 36,000) of the soluble fraction (cytoplasm) are labeled by the photoaffinity reagent and are specific for cyclic AMP. By analogy with other systems, these may be regulatory subunits of protein kinases. The mPDE of ghosts or plasma membrane fractions converts the reagent to 8-N3-[32P]AMP, which specifically photoaffinity labels a protein of Mr 42,000 associated with the cytoplasmic face of the plasma membrane."}
{"id": "PMID:228292", "title": "Enzymatic methyl esterification of specific glutamyl residue in corticotropin.", "content": "Ovine corticotropin (alpha s-ACTH) was enzymatically methylated with purified calf brain protein methylase II (protein O-methyltransferase; S-adenosyl-L-methionine: protein-carboxyl O-methyltransferase, EC 2.1.1.24) and S-adenosyl-L-[methyl-14C]methionine. After incubation for 60 min at 37 degrees C, 30 mol % of the hormone was methylated on the basis of the [14C]methyl incorporation. In order to assess the location of methylation, the modified peptide was digested with pepsin. Analytical results derived from studies on the peptic digest led to the suggestion that the alpha s-ACTH-(6--28) peptide fragment was esterified. Because there is only one available methylation site at Glu-28, these results indicate that Glu-28 of alpha s-ACTH was specifically methyl esterified to yield [Glu(OMe)28]-alpha s-ACTH.", "contents": "Enzymatic methyl esterification of specific glutamyl residue in corticotropin. Ovine corticotropin (alpha s-ACTH) was enzymatically methylated with purified calf brain protein methylase II (protein O-methyltransferase; S-adenosyl-L-methionine: protein-carboxyl O-methyltransferase, EC 2.1.1.24) and S-adenosyl-L-[methyl-14C]methionine. After incubation for 60 min at 37 degrees C, 30 mol % of the hormone was methylated on the basis of the [14C]methyl incorporation. In order to assess the location of methylation, the modified peptide was digested with pepsin. Analytical results derived from studies on the peptic digest led to the suggestion that the alpha s-ACTH-(6--28) peptide fragment was esterified. Because there is only one available methylation site at Glu-28, these results indicate that Glu-28 of alpha s-ACTH was specifically methyl esterified to yield [Glu(OMe)28]-alpha s-ACTH."}
{"id": "PMID:228293", "title": "Characterization of a histone-like protein extracted from yeast mitochondria.", "content": "Analysis of proteins isolated by affinity chromatography on DNA-cellulose from highly purified yeast mitochondria shows that these organelles do not contain histones but have in abundance a DNA-binding protein of 20,000 daltons. The purification yield of this protein, called HM, indicates that mitochondria have at least an equal mass of HM relative to DNA. The amino acid composition and its electrophoretic characterization reveal that HM, rich in lysine, is slightly basic and heat stable. HM appears to be coded by the yeast nucleus, as shown by its presence in several \"petite\" mutants. We have shown that HM, like histones or histone-like proteins, is able to introduce superhelical turns into circular relaxed DNA in the presence of a nicking-closing activity.", "contents": "Characterization of a histone-like protein extracted from yeast mitochondria. Analysis of proteins isolated by affinity chromatography on DNA-cellulose from highly purified yeast mitochondria shows that these organelles do not contain histones but have in abundance a DNA-binding protein of 20,000 daltons. The purification yield of this protein, called HM, indicates that mitochondria have at least an equal mass of HM relative to DNA. The amino acid composition and its electrophoretic characterization reveal that HM, rich in lysine, is slightly basic and heat stable. HM appears to be coded by the yeast nucleus, as shown by its presence in several \"petite\" mutants. We have shown that HM, like histones or histone-like proteins, is able to introduce superhelical turns into circular relaxed DNA in the presence of a nicking-closing activity."}
{"id": "PMID:228294", "title": "Oncogenicity of simian virus 40 deletion mutants that induce altered 17-kilodalton t-proteins.", "content": "Plaque-purified viable simian virus 40 deletion mutants containing deletions between map positions 0.54 and 0.59 induced tumors in 21--92% of LSH hamsters inoculated during the first 24 hr of life. HinfI restriction endonuclease digestion patterns of the genomes of virions rescued from the tumor cells and the distribution of simian virus 40 early proteins in these cells associated tumor induction with the inoculated mutants. These results imply that the DNA sequences comprising that portion of the early simian virus 40 genome between map positions 0.54 and 0.59 are not essential for simian virus 40 oncogenicity.", "contents": "Oncogenicity of simian virus 40 deletion mutants that induce altered 17-kilodalton t-proteins. Plaque-purified viable simian virus 40 deletion mutants containing deletions between map positions 0.54 and 0.59 induced tumors in 21--92% of LSH hamsters inoculated during the first 24 hr of life. HinfI restriction endonuclease digestion patterns of the genomes of virions rescued from the tumor cells and the distribution of simian virus 40 early proteins in these cells associated tumor induction with the inoculated mutants. These results imply that the DNA sequences comprising that portion of the early simian virus 40 genome between map positions 0.54 and 0.59 are not essential for simian virus 40 oncogenicity."}
{"id": "PMID:228295", "title": "A general priming system employing only dnaB protein and primase for DNA replication.", "content": "Priming of phage phi X174 DNA synthesis is effected simply by dnaB protein and primase when the DNA is not coated by single-strand binding protein (SSB). The five prepriming proteins (n,n',n'',i, and dnaC protein) required for priming a SSB-coated phi X174 DNA circle are dispensable. The dnaB protein-primase priming system is also active on uncoated phage G4 and M13 DNAs and on poly(dT). Multiple RNA primers, 10--60 nucleotides long, are transcribed with patterns distinctive for each DNA template. Formation of a stable dnaB protein.DNA complex in the presence of primase and ATP supports the hypothesis that dnaB protein provides a mobile replication promoter signal for primase.", "contents": "A general priming system employing only dnaB protein and primase for DNA replication. Priming of phage phi X174 DNA synthesis is effected simply by dnaB protein and primase when the DNA is not coated by single-strand binding protein (SSB). The five prepriming proteins (n,n',n'',i, and dnaC protein) required for priming a SSB-coated phi X174 DNA circle are dispensable. The dnaB protein-primase priming system is also active on uncoated phage G4 and M13 DNAs and on poly(dT). Multiple RNA primers, 10--60 nucleotides long, are transcribed with patterns distinctive for each DNA template. Formation of a stable dnaB protein.DNA complex in the presence of primase and ATP supports the hypothesis that dnaB protein provides a mobile replication promoter signal for primase."}
{"id": "PMID:228296", "title": "Splicing as a requirement for biogenesis of functional 16S mRNA of simian virus 40.", "content": "Simian virus 40 deletion mutants were constructed lacking specifically the intervening sequences for a late viral mRNA. The construction method involved the replacement of portions of the late simian virus 40 genes with the DNA segment from reverse transcription of the viral mRNAs. Restriction endonuclease cleavage and sequence analysis confirmed the precise structure of the mutant DNAs and demonstrated that they contained the genetic information for VP1, including all potential 5' ends for the late viral RNAs. Thus, the primary late transcription product(s) of this mutant should have the structure of functional 16S mRNAs. Complementation analysis as well as immunoprecipitation showed, however, that deletion of the intervening sequences from this mutant prevented the expression of VP1. The nature of this failure appears to be a defect in the posttranscriptional processing of the viral RNA. These results indicate that splicing is an essential function in the biogenesis of certain mRNAs.", "contents": "Splicing as a requirement for biogenesis of functional 16S mRNA of simian virus 40. Simian virus 40 deletion mutants were constructed lacking specifically the intervening sequences for a late viral mRNA. The construction method involved the replacement of portions of the late simian virus 40 genes with the DNA segment from reverse transcription of the viral mRNAs. Restriction endonuclease cleavage and sequence analysis confirmed the precise structure of the mutant DNAs and demonstrated that they contained the genetic information for VP1, including all potential 5' ends for the late viral RNAs. Thus, the primary late transcription product(s) of this mutant should have the structure of functional 16S mRNAs. Complementation analysis as well as immunoprecipitation showed, however, that deletion of the intervening sequences from this mutant prevented the expression of VP1. The nature of this failure appears to be a defect in the posttranscriptional processing of the viral RNA. These results indicate that splicing is an essential function in the biogenesis of certain mRNAs."}
{"id": "PMID:228297", "title": "Conserved primary sequences of the DNA terminal proteins of five different human adenovirus groups.", "content": "The 31 human adenoviruses (Ad) from five groups (A-E) whose DNAs are <20% homologous by molecular hybridization. Ad5 (group C) DNA contains a 55,000-dalton protein probably covalently bound to each 5' terminus. This covalently bound protein may be analogous to polypeptides found in other viral and nonviral systems that are covalently bound to genomic DNAs or RNAs and that are thought to function in DNA or RNA replication. Because of the importance of proteins linked to nucleic acids, we have investigated whether DNAs from all five groups of human adenoviruses have terminal proteins, as well as the peptide relationships among the different terminal proteins. We show here that DNAs from Ad12, 7, 2, 19, and 4, representing Ad groups A-E, respectively, all contain covalently bound proteins of about 55,000 daltons. To investigate the peptide relatedness among the terminal proteins, we prepared microgram quantities of covalently bound protein from Ads in groups A-E and compared their chymotryptic and tryptic (125)I-labeled peptide maps. We find that the covalently bound protein maps of the five Ad groups are highly related and possibly identical. On the other hand, the tryptic and chymotryptic peptide maps of the major virion protein II and the core proteins V and VII of groups B, C, and E Ads show considerable heterology. Assuming that the covalently bound protein is virally coded, the conserved primary sequence of these proteins suggests a major functional role for the protein in Ad replication. Because the genetic origin of the Ad covalently bound proteins is not established, our data are also consistent with the possibility that the protein is coded by a cellular gene.", "contents": "Conserved primary sequences of the DNA terminal proteins of five different human adenovirus groups. The 31 human adenoviruses (Ad) from five groups (A-E) whose DNAs are <20% homologous by molecular hybridization. Ad5 (group C) DNA contains a 55,000-dalton protein probably covalently bound to each 5' terminus. This covalently bound protein may be analogous to polypeptides found in other viral and nonviral systems that are covalently bound to genomic DNAs or RNAs and that are thought to function in DNA or RNA replication. Because of the importance of proteins linked to nucleic acids, we have investigated whether DNAs from all five groups of human adenoviruses have terminal proteins, as well as the peptide relationships among the different terminal proteins. We show here that DNAs from Ad12, 7, 2, 19, and 4, representing Ad groups A-E, respectively, all contain covalently bound proteins of about 55,000 daltons. To investigate the peptide relatedness among the terminal proteins, we prepared microgram quantities of covalently bound protein from Ads in groups A-E and compared their chymotryptic and tryptic (125)I-labeled peptide maps. We find that the covalently bound protein maps of the five Ad groups are highly related and possibly identical. On the other hand, the tryptic and chymotryptic peptide maps of the major virion protein II and the core proteins V and VII of groups B, C, and E Ads show considerable heterology. Assuming that the covalently bound protein is virally coded, the conserved primary sequence of these proteins suggests a major functional role for the protein in Ad replication. Because the genetic origin of the Ad covalently bound proteins is not established, our data are also consistent with the possibility that the protein is coded by a cellular gene."}
{"id": "PMID:228298", "title": "DNA synthesis in temperature-sensitive mutants of the cell cycle infected by polyoma virus and adenovirus.", "content": "tsAF8 cells are a temperature-sensitive (ts) mutant of BHK cells that are arrested in G1 at the nonpermissive temperature. When made quiescent by serum restriction, they can be stimulated to enter S phase by 10% serum at 34 degrees C but not at 40.6 degrees C. The same results can be obtained if quiescent cells are infected with polyoma virus or adenovirus 12 instead of serum. However, adenovirus 2 infection stimulates DNA synthesis in tsAF8 cells at both 34 degrees C and 40.6 degrees C. The DNA synthesized after adenovirus 2 infection has been shown to be cellular DNA by CsCl density centrifugation. By density labeling it can be shown that adenovirus 2-induced DNA synthesis is due to semiconservative replication. The difference between adenovirus 2 and polyoma (or serum) is also evident with another ts mutant of BHK cells, ts13 cells. These results open the possibility of identifying the viral or cellular mechanism at the basis of this difference in the induction of host DNA synthesis between adenovirus 2 and polyoma or serum.", "contents": "DNA synthesis in temperature-sensitive mutants of the cell cycle infected by polyoma virus and adenovirus. tsAF8 cells are a temperature-sensitive (ts) mutant of BHK cells that are arrested in G1 at the nonpermissive temperature. When made quiescent by serum restriction, they can be stimulated to enter S phase by 10% serum at 34 degrees C but not at 40.6 degrees C. The same results can be obtained if quiescent cells are infected with polyoma virus or adenovirus 12 instead of serum. However, adenovirus 2 infection stimulates DNA synthesis in tsAF8 cells at both 34 degrees C and 40.6 degrees C. The DNA synthesized after adenovirus 2 infection has been shown to be cellular DNA by CsCl density centrifugation. By density labeling it can be shown that adenovirus 2-induced DNA synthesis is due to semiconservative replication. The difference between adenovirus 2 and polyoma (or serum) is also evident with another ts mutant of BHK cells, ts13 cells. These results open the possibility of identifying the viral or cellular mechanism at the basis of this difference in the induction of host DNA synthesis between adenovirus 2 and polyoma or serum."}
{"id": "PMID:228299", "title": "Phospholipid methylation stimulates lactogenic binding in mouse mammary gland membranes.", "content": "Addition of the methyl donor S-adenosyl-L-methionine to membranes prepared from mammary glands of lactating mice results in increased binding of 25I-labeled human growth hormone to the lactogenic receptors. This stimulation is dose dependent and specific for S-adenosyl-L-methionine and is partially inhibited by simultaneous addition of S-adenosyl-homocysteine to the reaction. Pretreatment of the membranes with S-adenosyl-L-methionine for 30 min at 37 degrees C is sufficient to cause enhanced binding. Scatchard analysis shows that treatment with S-adenosyl-L-methionine results in an increase in the number of lactogenic binding sites without changing the apparent affinity constant for 125I-labeled human growth hormone. The increase in the number of binding sites is believed to be due to alteration in the phospholipid composition of the membrane because methylation of phospholipids is observed under these conditions.", "contents": "Phospholipid methylation stimulates lactogenic binding in mouse mammary gland membranes. Addition of the methyl donor S-adenosyl-L-methionine to membranes prepared from mammary glands of lactating mice results in increased binding of 25I-labeled human growth hormone to the lactogenic receptors. This stimulation is dose dependent and specific for S-adenosyl-L-methionine and is partially inhibited by simultaneous addition of S-adenosyl-homocysteine to the reaction. Pretreatment of the membranes with S-adenosyl-L-methionine for 30 min at 37 degrees C is sufficient to cause enhanced binding. Scatchard analysis shows that treatment with S-adenosyl-L-methionine results in an increase in the number of lactogenic binding sites without changing the apparent affinity constant for 125I-labeled human growth hormone. The increase in the number of binding sites is believed to be due to alteration in the phospholipid composition of the membrane because methylation of phospholipids is observed under these conditions."}
{"id": "PMID:228300", "title": "Molecular genetics of herpes simplex virus: the terminal a sequences of the L and S components are obligatorily identical and constitute a part of a structural gene mapping predominantly in the S component.", "content": "In herpes simplex virus 1 (HSV-1) DNA, a small sequence, designated the a sequence, flanks the reiterated sequences at the ends of both the L and S components. The a sequence is the only sequence shared by the termini of all isomeric arrangements of HSV-1 DNA that arise from inversions of the covalently linked L and S components. We report that the a sequence, although present in both components, is a part of a structural gene mapping predominantly in the reiterated sequences of the S component. This conclusion is based on the observations that the mutant HSV-1(13)tsC75 is rescued by transfection of cells with the mutant DNA and any one of the four terminal or four L-S junction fragments of wild-type DNA. Furthermore, in doubly infected cells, this mutant shows little or no recombination or complementation with other ts mutants previously mapped within the reiterated sequences of the S component. Because it is otherwise difficult to explain the isolation of a mutant with several independent, equivalent mutations, the data argue for a mechanism that maintains the identity of the multiple copies of the a sequence.The paradox arising from the two observations that all termini rescue the ts mutant but that in coinfection tests the ts lesion is closely linked to the reiterated sequences of the S component could be accounted for by postulating that either recombination occurs while the DNA is in a circular form-in which case all a sequences would be adjacent to the reiterated sequence of the S component-or recombination can occur while the DNA is in a linear form. In this case the only effective substitution of the a sequence that is perpetuated is the one occurring at the L-S junction or in the S component. In light of the observations that tsC75 and the other mutants tested in this study map in the reiterated sequences and fail to yield appreciable recombinational frequencies, it is unlikely that isomerization of the DNA occurs by intramolecular recombination between reiterated sequences.", "contents": "Molecular genetics of herpes simplex virus: the terminal a sequences of the L and S components are obligatorily identical and constitute a part of a structural gene mapping predominantly in the S component. In herpes simplex virus 1 (HSV-1) DNA, a small sequence, designated the a sequence, flanks the reiterated sequences at the ends of both the L and S components. The a sequence is the only sequence shared by the termini of all isomeric arrangements of HSV-1 DNA that arise from inversions of the covalently linked L and S components. We report that the a sequence, although present in both components, is a part of a structural gene mapping predominantly in the reiterated sequences of the S component. This conclusion is based on the observations that the mutant HSV-1(13)tsC75 is rescued by transfection of cells with the mutant DNA and any one of the four terminal or four L-S junction fragments of wild-type DNA. Furthermore, in doubly infected cells, this mutant shows little or no recombination or complementation with other ts mutants previously mapped within the reiterated sequences of the S component. Because it is otherwise difficult to explain the isolation of a mutant with several independent, equivalent mutations, the data argue for a mechanism that maintains the identity of the multiple copies of the a sequence.The paradox arising from the two observations that all termini rescue the ts mutant but that in coinfection tests the ts lesion is closely linked to the reiterated sequences of the S component could be accounted for by postulating that either recombination occurs while the DNA is in a circular form-in which case all a sequences would be adjacent to the reiterated sequence of the S component-or recombination can occur while the DNA is in a linear form. In this case the only effective substitution of the a sequence that is perpetuated is the one occurring at the L-S junction or in the S component. In light of the observations that tsC75 and the other mutants tested in this study map in the reiterated sequences and fail to yield appreciable recombinational frequencies, it is unlikely that isomerization of the DNA occurs by intramolecular recombination between reiterated sequences."}
{"id": "PMID:228301", "title": "Identification of DNA fragments carrying ecotropic proviruses of AKR mice.", "content": "The proviruses of the N-tropic, ecotropic virus (AKV) of AKR mice (Akv-1, Akv-2) have been studied by the Southern gel--filter transfer technique. These proviruses can be detected by cleavage of cell DNA by BamHI endonuclease, which yields characteristic subgenomic DNA fragments upon cleavage of this type of provirus. Proviruses integrated into different sites in the mouse genome can be resolved with EcoRI endonuclease, which does not cleave the AKV proviruses. Use of congenic and backcrossed mice and a radioactive DNA probe enriched for AKV sequences has allowed identification of the EcoRI fragments carrying the proviruses of the genetically defined Akv-1 and Akv-2 loci. Novel proviruses introduced by superinfection of cultured AKR cells with AKV and present in leukemic cells from AKR mice have also been identified. Comparison of substrains of AKR mice indicates some heterogeneity in their spectra of proviruses.", "contents": "Identification of DNA fragments carrying ecotropic proviruses of AKR mice. The proviruses of the N-tropic, ecotropic virus (AKV) of AKR mice (Akv-1, Akv-2) have been studied by the Southern gel--filter transfer technique. These proviruses can be detected by cleavage of cell DNA by BamHI endonuclease, which yields characteristic subgenomic DNA fragments upon cleavage of this type of provirus. Proviruses integrated into different sites in the mouse genome can be resolved with EcoRI endonuclease, which does not cleave the AKV proviruses. Use of congenic and backcrossed mice and a radioactive DNA probe enriched for AKV sequences has allowed identification of the EcoRI fragments carrying the proviruses of the genetically defined Akv-1 and Akv-2 loci. Novel proviruses introduced by superinfection of cultured AKR cells with AKV and present in leukemic cells from AKR mice have also been identified. Comparison of substrains of AKR mice indicates some heterogeneity in their spectra of proviruses."}
{"id": "PMID:228302", "title": "Catabolite inactivation of gluconeogenic enzymes in mutants of yeast deficient in proteinase B.", "content": "Strains of Saccharomyces cerevisiae bearing nonsense mutations in the structural gene for proteinase B (EC 3.4.22.9) have been examined for the ability to make the transition from growth on acetate to growth on glucose and for the ability to inactivate three glucoeogenic enzymes during the transition because proteinase B has been proposed by others to be responsible for the inactivation of the three enzymes during the growth transition. The mutant strains make the growth transition normally. Catabolite inactivation of hexosediphosphatase (D-fructose-1,6-biphosphate 1-phosphohydrolase, EC 3.1.3.11), malate dehydrogenase (L-malate:NAD+ oxidoreductase, EC 1.1.1.37), and phosphoenolpyruvate carboxykinase (ATP) [ATP:oxaloacetate carboxy-lyase (transphosphorylating), EC 4.1.1.49] occurred in prb1 mutants with kinetics similar to those seen in wild-type strains. We infer that proteinase B activity is not essential for the process of catabolite inactivation.", "contents": "Catabolite inactivation of gluconeogenic enzymes in mutants of yeast deficient in proteinase B. Strains of Saccharomyces cerevisiae bearing nonsense mutations in the structural gene for proteinase B (EC 3.4.22.9) have been examined for the ability to make the transition from growth on acetate to growth on glucose and for the ability to inactivate three glucoeogenic enzymes during the transition because proteinase B has been proposed by others to be responsible for the inactivation of the three enzymes during the growth transition. The mutant strains make the growth transition normally. Catabolite inactivation of hexosediphosphatase (D-fructose-1,6-biphosphate 1-phosphohydrolase, EC 3.1.3.11), malate dehydrogenase (L-malate:NAD+ oxidoreductase, EC 1.1.1.37), and phosphoenolpyruvate carboxykinase (ATP) [ATP:oxaloacetate carboxy-lyase (transphosphorylating), EC 4.1.1.49] occurred in prb1 mutants with kinetics similar to those seen in wild-type strains. We infer that proteinase B activity is not essential for the process of catabolite inactivation."}
{"id": "PMID:228303", "title": "Selective and unidirectional membrane redistribution of an H-2 antigen with an antibody-clustered viral antigen: relationship to mechanisms of cytotoxic T-cell interactions.", "content": "We have studied the co-redistribution of vesicular stomatitis virus (VSV) antigen and of individual H-2 antigens on the surfaces of mouse cells, and in parallel we have also used these VSV-infected cells as targets in cytotoxic T-cell killing experiments. Antibody-induced patching and capping of the VSV antigen caused an extensive co-patching and co-capping of the H-2Kb antigen but not of the H-2Db antigen. In reciprocal experiments, the antibody-induced patching of the H-2Kb or H-2Db antigen did not result in a co-patching of the VSV antigen. Radioimmunoassays showed that the relative numbers of H-2Kb, H-2Db, and VSV antigens on the surfaces of the cells exhibiting such nonreciprocal co-redistributions were closely similar. Furthermore, the H-2 restricted cytotoxic T-cell lysis of these target cells showed a marked preference for H-2Kb compared to H-2Db compatibility. We propose that the VSV and H-2 antigens are molecularly independent entities in the unpreturbed target cell membrane but that the antibody-induced clustering of the VSV antigen causes a selective and unidirectional co-redistribution (which we designate as syn-capping) of H-2Kb with the VSV antigen clusters. It is suggested that such a T-cell-induced syn-capping process involving an antigen and an H-2 molecule on the target cell may play a critical role in the mechanism of cytotoxic T-cell killing.", "contents": "Selective and unidirectional membrane redistribution of an H-2 antigen with an antibody-clustered viral antigen: relationship to mechanisms of cytotoxic T-cell interactions. We have studied the co-redistribution of vesicular stomatitis virus (VSV) antigen and of individual H-2 antigens on the surfaces of mouse cells, and in parallel we have also used these VSV-infected cells as targets in cytotoxic T-cell killing experiments. Antibody-induced patching and capping of the VSV antigen caused an extensive co-patching and co-capping of the H-2Kb antigen but not of the H-2Db antigen. In reciprocal experiments, the antibody-induced patching of the H-2Kb or H-2Db antigen did not result in a co-patching of the VSV antigen. Radioimmunoassays showed that the relative numbers of H-2Kb, H-2Db, and VSV antigens on the surfaces of the cells exhibiting such nonreciprocal co-redistributions were closely similar. Furthermore, the H-2 restricted cytotoxic T-cell lysis of these target cells showed a marked preference for H-2Kb compared to H-2Db compatibility. We propose that the VSV and H-2 antigens are molecularly independent entities in the unpreturbed target cell membrane but that the antibody-induced clustering of the VSV antigen causes a selective and unidirectional co-redistribution (which we designate as syn-capping) of H-2Kb with the VSV antigen clusters. It is suggested that such a T-cell-induced syn-capping process involving an antigen and an H-2 molecule on the target cell may play a critical role in the mechanism of cytotoxic T-cell killing."}
{"id": "PMID:228304", "title": "Sodium transport inhibitor from bovine hypothalamus.", "content": "A low molecular weight, basic, nonpeptidic factor that possesses sodium transport inhibitory properties has been prepared from bovine hypothalamus by acid/acetone extraction and gel filtration. Concentration and partial purification was achieved by ion-exchange chromatography. This substance inhibits active Na+ transport across anuran membranes, inhibits ouabain binding to frog urinary bladder, and directly inhibits renal Na+,K+-ATPase. This substance thus possesses the putative characteristics of a natriuretic factor of hypothalamic origin.", "contents": "Sodium transport inhibitor from bovine hypothalamus. A low molecular weight, basic, nonpeptidic factor that possesses sodium transport inhibitory properties has been prepared from bovine hypothalamus by acid/acetone extraction and gel filtration. Concentration and partial purification was achieved by ion-exchange chromatography. This substance inhibits active Na+ transport across anuran membranes, inhibits ouabain binding to frog urinary bladder, and directly inhibits renal Na+,K+-ATPase. This substance thus possesses the putative characteristics of a natriuretic factor of hypothalamic origin."}
{"id": "PMID:228305", "title": "Endogenous digitalis-like activity in mammalian brain.", "content": "A fraction of brain has been prepared that contains a substance mimicking actions of the digitalis glycosides. It both blocks the binding of [3H]ouabain to Na+,K+-ATPase (ATP phosphohydrolase, EC 3.6.1.3) and inhibits the uptake of 86Rb+ into human erythrocytes. Partial isolation was achieved by Sephadex G-10 fractionation and subsequent desalting. This activity is potentially capable of regulating ionic fluxes and concentration gradients across the cell membrane.", "contents": "Endogenous digitalis-like activity in mammalian brain. A fraction of brain has been prepared that contains a substance mimicking actions of the digitalis glycosides. It both blocks the binding of [3H]ouabain to Na+,K+-ATPase (ATP phosphohydrolase, EC 3.6.1.3) and inhibits the uptake of 86Rb+ into human erythrocytes. Partial isolation was achieved by Sephadex G-10 fractionation and subsequent desalting. This activity is potentially capable of regulating ionic fluxes and concentration gradients across the cell membrane."}
{"id": "PMID:228318", "title": "Clonidine reverses the amnesia induced by dopamine beta hydroxylase inhibition.", "content": "The role of noradrenergic (NE) mechanisms in amnesia induced by the dopamine-beta-hydroxylase (DBH) inhibitor, diethyldithiocarbamate (DEDTC) was examined by studying the antiamnestic characteristics of the alpha-NE receptor stimulator clonidine. DEDTC (250 mg/kg) administered 3 hr prior to training to C57BL/6J mice resulted in marked deficits when retention of a multiple trial food motivated spatial discrimination task was measured 24 hr after learning. Investigation of the temporal aspects of recovery indicated that the agonist was an effective antiamnestic agent when administered 0, 1, 3, 21 and 23 hr after training. No recovery was observed when the drug was administered 6 and 18 hr posttraining. A dose response study of the effectiveness of clonidine administered 1 hr prior to testing indicated recovery of memory at doses ranging from 10-500 microgram/kg. The clonidine induced recovery was not a result of general performance facilitation, but specific to the memory tested. In addition, the clonidine effect was pharmacologically specific to its actions on NE receptors, as recovery was blocked by pre-treatment with the alpha-NE antagonist, phentolamine. No recovery from DEDTC induced amnesia was seen with post-training or pre-test injection of d-amphetamine.", "contents": "Clonidine reverses the amnesia induced by dopamine beta hydroxylase inhibition. The role of noradrenergic (NE) mechanisms in amnesia induced by the dopamine-beta-hydroxylase (DBH) inhibitor, diethyldithiocarbamate (DEDTC) was examined by studying the antiamnestic characteristics of the alpha-NE receptor stimulator clonidine. DEDTC (250 mg/kg) administered 3 hr prior to training to C57BL/6J mice resulted in marked deficits when retention of a multiple trial food motivated spatial discrimination task was measured 24 hr after learning. Investigation of the temporal aspects of recovery indicated that the agonist was an effective antiamnestic agent when administered 0, 1, 3, 21 and 23 hr after training. No recovery was observed when the drug was administered 6 and 18 hr posttraining. A dose response study of the effectiveness of clonidine administered 1 hr prior to testing indicated recovery of memory at doses ranging from 10-500 microgram/kg. The clonidine induced recovery was not a result of general performance facilitation, but specific to the memory tested. In addition, the clonidine effect was pharmacologically specific to its actions on NE receptors, as recovery was blocked by pre-treatment with the alpha-NE antagonist, phentolamine. No recovery from DEDTC induced amnesia was seen with post-training or pre-test injection of d-amphetamine."}
{"id": "PMID:228337", "title": "Effects of two neuroleptic drugs on focal somatoparietal rhythms in free awake cats.", "content": "In freely moving cats, systemic administration of Chlorpromazine (CPZ) and Haloperidol (HP), two neuroleptics which presumably block catecholamine receptors, leads to a suppression of the waking mu-type rhythms. There is a clear difference, however, in that CPZ leads to slow wave sleep while HP only induces sustained drowsiness. The difference in their action is tentatively explained by their differential effect on an enzyme that is not involved in the metabolism of biogenic amines, tryptophan pyrrolase. We suggest that it is through this pathway that CPZ might increase and HP might decrease brain tryptophan and thereby lead to opposite changes in brain 5-HT content.", "contents": "Effects of two neuroleptic drugs on focal somatoparietal rhythms in free awake cats. In freely moving cats, systemic administration of Chlorpromazine (CPZ) and Haloperidol (HP), two neuroleptics which presumably block catecholamine receptors, leads to a suppression of the waking mu-type rhythms. There is a clear difference, however, in that CPZ leads to slow wave sleep while HP only induces sustained drowsiness. The difference in their action is tentatively explained by their differential effect on an enzyme that is not involved in the metabolism of biogenic amines, tryptophan pyrrolase. We suggest that it is through this pathway that CPZ might increase and HP might decrease brain tryptophan and thereby lead to opposite changes in brain 5-HT content."}
{"id": "PMID:228343", "title": "[The small nodular pattern of primary and secondary lung neoplasia (author's transl)].", "content": "The radiographic pattern of multiple disseminated pulmonary nodules is especially difficult to interpret. There are some special forms of primary and secondary lung neoplasia which present as small nodular lesions of various distribution. Alveolar cell carcinoma and bronchogenic carcinoma with intracanalicular spread or small nodular or even miliary type lesions serve as well known examples. The radiographic morphology of small disseminated nodular foci of pulmonary metastases of primary lung tumors as well as of tumors outside the lung is being discussed. Even very subtle film analysis, observation of all radiological signs, as well as the clinical picture and the laboratory data, provides only limited help for the differential diagnosis.", "contents": "[The small nodular pattern of primary and secondary lung neoplasia (author's transl)]. The radiographic pattern of multiple disseminated pulmonary nodules is especially difficult to interpret. There are some special forms of primary and secondary lung neoplasia which present as small nodular lesions of various distribution. Alveolar cell carcinoma and bronchogenic carcinoma with intracanalicular spread or small nodular or even miliary type lesions serve as well known examples. The radiographic morphology of small disseminated nodular foci of pulmonary metastases of primary lung tumors as well as of tumors outside the lung is being discussed. Even very subtle film analysis, observation of all radiological signs, as well as the clinical picture and the laboratory data, provides only limited help for the differential diagnosis."}
{"id": "PMID:228344", "title": "[Primary and secondary perosteal reactions (author's transl)].", "content": "Radiological and histological comparative analysis of the morphological changes of periosteal reaction. A distinction is made between secondary periosteal reaction (so called periostitis ossificans or osseous periostosis), primary periosteal lesions (due to inflammation, trauma, fibrosis and neoplasia) and soft tissue lesions involving the adjacent periosteum. Secondary periosteal reactions are most frequent, indicating the need for search of its cause. Here biopsy of the periosteal reaction is often important for establishing an early diagnosis.", "contents": "[Primary and secondary perosteal reactions (author's transl)]. Radiological and histological comparative analysis of the morphological changes of periosteal reaction. A distinction is made between secondary periosteal reaction (so called periostitis ossificans or osseous periostosis), primary periosteal lesions (due to inflammation, trauma, fibrosis and neoplasia) and soft tissue lesions involving the adjacent periosteum. Secondary periosteal reactions are most frequent, indicating the need for search of its cause. Here biopsy of the periosteal reaction is often important for establishing an early diagnosis."}
{"id": "PMID:228345", "title": "[Radiographic findings of periosteal reactions in systemic bone disorders (author's transl)].", "content": "Periosteal reaction is frequently the first sign of systemic disease affecting the skeleton, including generalized osteopathia. It can be generalized, focal, monostotic or polyostotic and shows solid, lamellary or interrrupted spiculae-like reaction. A reliable diagnosis is possible from the interpretation of these changes, as for instance with spiculae: Very dense and evenly arranged spiculae are only seen in hemolytic anemias and metastases of neurogenic tumors. Onionskin like periosteal reaction with simultaneous transformation of the diaphyseal cortex are difficult to interpret. However, in case of hyperparathyreoidism, subperiosteal resorption and transformation of the diaphyseal cortex permit precise diagnosis. Follow-up examinations have prognostic and therapeutic value. The knowledge of the different morphology of periosteal reaction associated with systemic disease (including generalized osteopathias) is important in diagnostic radiology.", "contents": "[Radiographic findings of periosteal reactions in systemic bone disorders (author's transl)]. Periosteal reaction is frequently the first sign of systemic disease affecting the skeleton, including generalized osteopathia. It can be generalized, focal, monostotic or polyostotic and shows solid, lamellary or interrrupted spiculae-like reaction. A reliable diagnosis is possible from the interpretation of these changes, as for instance with spiculae: Very dense and evenly arranged spiculae are only seen in hemolytic anemias and metastases of neurogenic tumors. Onionskin like periosteal reaction with simultaneous transformation of the diaphyseal cortex are difficult to interpret. However, in case of hyperparathyreoidism, subperiosteal resorption and transformation of the diaphyseal cortex permit precise diagnosis. Follow-up examinations have prognostic and therapeutic value. The knowledge of the different morphology of periosteal reaction associated with systemic disease (including generalized osteopathias) is important in diagnostic radiology."}
{"id": "PMID:228346", "title": "Pulmonary interstitial changes following bone marrow transplantation.", "content": "Observations of 20 consecutive bone marrow transplantation recipients disclosed two distinctive categories of pulmonary interstitial changes. Interstitial infiltrates occurring less than 14 days after transplantation were observed in 13 of 20 patients and are believed to represent pulmonary edema. A late pulmonary interstitial process, which appears more than 30 days following transplantation (median 57 days), was encountered in 10 of 14 patients with successful grafts; the late changes represent interstitial pneumonia, a common cause of morbidity and mortality following bone marrow transplantation. It is probably attributable to a combination of factors including the preparatory chemotherapy and radiotherapy, and delayed immunologic reconstitution following transplantation.", "contents": "Pulmonary interstitial changes following bone marrow transplantation. Observations of 20 consecutive bone marrow transplantation recipients disclosed two distinctive categories of pulmonary interstitial changes. Interstitial infiltrates occurring less than 14 days after transplantation were observed in 13 of 20 patients and are believed to represent pulmonary edema. A late pulmonary interstitial process, which appears more than 30 days following transplantation (median 57 days), was encountered in 10 of 14 patients with successful grafts; the late changes represent interstitial pneumonia, a common cause of morbidity and mortality following bone marrow transplantation. It is probably attributable to a combination of factors including the preparatory chemotherapy and radiotherapy, and delayed immunologic reconstitution following transplantation."}
{"id": "PMID:228347", "title": "99mTc-PP and 67Ga imaging following insertion of orthopedic devices.", "content": "Deposition of 67Ga in bone does not explicitly imply osteomyelitis. Osteomyelitis complicating insertion of orthopedic devices is manifested by lack of congruence in the distribution patterns of 99mTc-PP and 67Ga. Congruent patterns can reflect the increased bone reaction to implantation or loosening of the device, not necessarily osteomyelitis. Both (a) nonseptic synovitis secondary to reactive bursa formation and (b) cellulitis exhibit an affinity for 67Ga and virtually none for 99mTc-PP, whereas the reverse is true for heterotopic bone. Thus combined sequential 99mTc-PP/67Ga imaging is necessary for evaluation of complications associated with internal orthopedic devices.", "contents": "99mTc-PP and 67Ga imaging following insertion of orthopedic devices. Deposition of 67Ga in bone does not explicitly imply osteomyelitis. Osteomyelitis complicating insertion of orthopedic devices is manifested by lack of congruence in the distribution patterns of 99mTc-PP and 67Ga. Congruent patterns can reflect the increased bone reaction to implantation or loosening of the device, not necessarily osteomyelitis. Both (a) nonseptic synovitis secondary to reactive bursa formation and (b) cellulitis exhibit an affinity for 67Ga and virtually none for 99mTc-PP, whereas the reverse is true for heterotopic bone. Thus combined sequential 99mTc-PP/67Ga imaging is necessary for evaluation of complications associated with internal orthopedic devices."}
{"id": "PMID:228353", "title": "Effects of prostaglandins on the action of luteinizing hormone in dispersed rat intestitial cells.", "content": "Prostaglandins E1, E2, A1 and A2 at 10(-5) and 10(-4)M stimulated basal testosterone production in dispersed rat interstitial cells in vitro. They effectively inhibited steroidogenesis induced by ovine pituitary luteinizing hormone (LH) (0.2 nM), dibutyryl cyclic AMP-(DBC 0-5 mM), and cholera toxin (100 ng). PGF2 alpha (10(-3) to 10(-12)M) had no effect on either basal or hormonal or non-hormonal stimulated steroidogenesis in the cells. PGA1 and PGA2 were more effective inhibitors than PGE1 and E2. None of the PG's had any influence on 125I LH-receptor interaction. In view of this and the inhibition of DBC stimulated testosterone production, it may be suggested that the PG inhibition lies beyond the receptor-cyclic AMP formation step.", "contents": "Effects of prostaglandins on the action of luteinizing hormone in dispersed rat intestitial cells. Prostaglandins E1, E2, A1 and A2 at 10(-5) and 10(-4)M stimulated basal testosterone production in dispersed rat interstitial cells in vitro. They effectively inhibited steroidogenesis induced by ovine pituitary luteinizing hormone (LH) (0.2 nM), dibutyryl cyclic AMP-(DBC 0-5 mM), and cholera toxin (100 ng). PGF2 alpha (10(-3) to 10(-12)M) had no effect on either basal or hormonal or non-hormonal stimulated steroidogenesis in the cells. PGA1 and PGA2 were more effective inhibitors than PGE1 and E2. None of the PG's had any influence on 125I LH-receptor interaction. In view of this and the inhibition of DBC stimulated testosterone production, it may be suggested that the PG inhibition lies beyond the receptor-cyclic AMP formation step."}
{"id": "PMID:228363", "title": "Studies on the mechanism of the hypotensive action of SQ-14225, an angiotensin-converting enzyme inhibitor in anesthetized dogs.", "content": "Intravenous administration of SQ-14225, an angiotensin-converting enzyme inhibitor, to pentobarbital-anesthetized dogs resulted in significant decrease in the arterial blood pressure with no changes in the heart rate. Pressure-flow curves obtained in the perfused hind limb vasculature were shifted significantly to the right following SQ-14225 indicating a decrease in the hind limb vascular resistance. Neither the denervation of the hind limb nor bilateral nephrectomy prevented the decrease in the hind limb vascular resistance produced by SQ-14225 indicating that the vasodilator action of this agent was unrelated to either the sympathetic nervous system or the renal renin-angiotensin system. The reflex vasodilatation in the hind limb observed during the administration of pressor agents was significantly attenuated by SQ-14225. Similarly this agent also antagonized the reflex increases in the systemic blood pressure, hind limb perfusion pressure and heart rate observed during bilateral carotid occlusion. These results suggest that the hypotensive action of SQ-14225 in the pentobarbital-anesthetized dog may be unrelated to the renal renin-angiotensin system.", "contents": "Studies on the mechanism of the hypotensive action of SQ-14225, an angiotensin-converting enzyme inhibitor in anesthetized dogs. Intravenous administration of SQ-14225, an angiotensin-converting enzyme inhibitor, to pentobarbital-anesthetized dogs resulted in significant decrease in the arterial blood pressure with no changes in the heart rate. Pressure-flow curves obtained in the perfused hind limb vasculature were shifted significantly to the right following SQ-14225 indicating a decrease in the hind limb vascular resistance. Neither the denervation of the hind limb nor bilateral nephrectomy prevented the decrease in the hind limb vascular resistance produced by SQ-14225 indicating that the vasodilator action of this agent was unrelated to either the sympathetic nervous system or the renal renin-angiotensin system. The reflex vasodilatation in the hind limb observed during the administration of pressor agents was significantly attenuated by SQ-14225. Similarly this agent also antagonized the reflex increases in the systemic blood pressure, hind limb perfusion pressure and heart rate observed during bilateral carotid occlusion. These results suggest that the hypotensive action of SQ-14225 in the pentobarbital-anesthetized dog may be unrelated to the renal renin-angiotensin system."}
{"id": "PMID:228364", "title": "Effect of delta 9-tetrahydrocannabinol on synaptic transmission in the electric eel electroplaque.", "content": "When the innervated membrane of the electric eel electroplaque is exposed to concentrations of delta 9-tetracannabinol of 50 to 100 microM synaptic transmission is blocked in approximately 30 minutes. During the block, the chemosensitivity of the innervated membrane to cholinergic agonists remains unaltered. Direct stimulation of the innervated membrane after synaptic transmission had failed did not elicit any postsynaptic membrane action potentials. The passing of hyperpolarizing currents across the electroplaque caused the nerve terminals which innervate the electroplaque to produce subthreshold potentials which resemble endplate potentials with a prolonged falling phase. With further incubation in the tetrahydrocannabinol solution the subthreshold potentials decreased in size and eventually disappeared. These results indicate that delta 9-tetrahydrocannabinol does not affect the acetylcholine-mediated membrane permeability changes, but instead, reduces the excitability of nonsynaptic membrane of both the pre- and postsynaptic elements.", "contents": "Effect of delta 9-tetrahydrocannabinol on synaptic transmission in the electric eel electroplaque. When the innervated membrane of the electric eel electroplaque is exposed to concentrations of delta 9-tetracannabinol of 50 to 100 microM synaptic transmission is blocked in approximately 30 minutes. During the block, the chemosensitivity of the innervated membrane to cholinergic agonists remains unaltered. Direct stimulation of the innervated membrane after synaptic transmission had failed did not elicit any postsynaptic membrane action potentials. The passing of hyperpolarizing currents across the electroplaque caused the nerve terminals which innervate the electroplaque to produce subthreshold potentials which resemble endplate potentials with a prolonged falling phase. With further incubation in the tetrahydrocannabinol solution the subthreshold potentials decreased in size and eventually disappeared. These results indicate that delta 9-tetrahydrocannabinol does not affect the acetylcholine-mediated membrane permeability changes, but instead, reduces the excitability of nonsynaptic membrane of both the pre- and postsynaptic elements."}
{"id": "PMID:228365", "title": "Preliminary observations on transplacental infection of bluetongue virus in sheep-a possible overwintering mechanism.", "content": "Sheep infected mid-gestation with bluetongue virus type 4 and type 16 produced clinically normal lambs that were viraemic at birth. Viraemia persisted for two months in some lambs even though they received colostrum. It is suggested that transplacental infection of bluetongue virus in sheep may be an overwintering mechanism for the virus in some areas of the world.", "contents": "Preliminary observations on transplacental infection of bluetongue virus in sheep-a possible overwintering mechanism. Sheep infected mid-gestation with bluetongue virus type 4 and type 16 produced clinically normal lambs that were viraemic at birth. Viraemia persisted for two months in some lambs even though they received colostrum. It is suggested that transplacental infection of bluetongue virus in sheep may be an overwintering mechanism for the virus in some areas of the world."}
{"id": "PMID:228366", "title": "PAS-positive inclusions in the alveolar type II cells of the caprine lung.", "content": "Histochemical analysis of inclusions in the alveolar type II cells was done with the alcian blue-PAS technique. PAS-positive inclusions, which were absent in the sheep and buffalo, were detected in the alveolar type II cells of the goat lung. Mixed diamine-sodium chloride did not stain these inclusions which also showed orthochromatic blue reaction with toluidine blue. The high percentage of alveolar type II cells showing these inclusions suggested that this difference could be explained by the environmental habitat of the goat.", "contents": "PAS-positive inclusions in the alveolar type II cells of the caprine lung. Histochemical analysis of inclusions in the alveolar type II cells was done with the alcian blue-PAS technique. PAS-positive inclusions, which were absent in the sheep and buffalo, were detected in the alveolar type II cells of the goat lung. Mixed diamine-sodium chloride did not stain these inclusions which also showed orthochromatic blue reaction with toluidine blue. The high percentage of alveolar type II cells showing these inclusions suggested that this difference could be explained by the environmental habitat of the goat."}
{"id": "PMID:228367", "title": "The aetiology of diarrhoea in pigs weaned at two days of age.", "content": "When pigs are weaned at two days of age large numbers of Excherichia coli appear in the anterior gut and the incidence of diarrhoea rises. The two phenomena do not appear to be directly related because the strains of E coli isolated are not serotypes previously found to be associated with neonatal pig scouring. Representative strains of the non-enteropathogenic serotypes did not produce enterotoxin and did not adhere to small intestine brush borders. Moreover when antibiotics were fed to eliminate E coli from the gut, the pigs still scoured. Rotavirus was detected in the gut contents and gut epithelium of scouring pigs and a bacteria-free filtrate of gut contents produced diarrhoea when administered to germ-free pigs. It is suggested that rotavirus may be one of the causes of the scouring seen shortly after weaning pigs at two days of age.", "contents": "The aetiology of diarrhoea in pigs weaned at two days of age. When pigs are weaned at two days of age large numbers of Excherichia coli appear in the anterior gut and the incidence of diarrhoea rises. The two phenomena do not appear to be directly related because the strains of E coli isolated are not serotypes previously found to be associated with neonatal pig scouring. Representative strains of the non-enteropathogenic serotypes did not produce enterotoxin and did not adhere to small intestine brush borders. Moreover when antibiotics were fed to eliminate E coli from the gut, the pigs still scoured. Rotavirus was detected in the gut contents and gut epithelium of scouring pigs and a bacteria-free filtrate of gut contents produced diarrhoea when administered to germ-free pigs. It is suggested that rotavirus may be one of the causes of the scouring seen shortly after weaning pigs at two days of age."}
{"id": "PMID:228368", "title": "Replication of turkey herpesvirus and Marek's disease virus in chick embryo skin organ culture.", "content": "Turkey herpesvirus (HVT) and an attenuated Marek's disease virus (MDV) replicated in organ cultures of chick embryo skin as assessed by immunofluorescence and/or electron microscopy. HVT-specific immunofluorescent antigen was detected in the feather follicle epithelium (FFE) and in the surface layer of the skin epidermis. Electron microscopy of infected explants revealed herpes-type cytopathology. Immature particles of both viruses appeared first in the nucleus. Oval or horseshoe-shaped non-enveloped particles of HVT and enveloped virions of MDV were seen in the cytoplasm of some transitional cells. The difference in the ability of HVT and MDV to form an envelope was believed to account for the difference in their transmissibility in chickens. The results indicated that HVT replicated in the FFE and in the epidermis of the skin. However, attempts to localise the site(s) of MDV replication by electron microscopy were unsuccessful.", "contents": "Replication of turkey herpesvirus and Marek's disease virus in chick embryo skin organ culture. Turkey herpesvirus (HVT) and an attenuated Marek's disease virus (MDV) replicated in organ cultures of chick embryo skin as assessed by immunofluorescence and/or electron microscopy. HVT-specific immunofluorescent antigen was detected in the feather follicle epithelium (FFE) and in the surface layer of the skin epidermis. Electron microscopy of infected explants revealed herpes-type cytopathology. Immature particles of both viruses appeared first in the nucleus. Oval or horseshoe-shaped non-enveloped particles of HVT and enveloped virions of MDV were seen in the cytoplasm of some transitional cells. The difference in the ability of HVT and MDV to form an envelope was believed to account for the difference in their transmissibility in chickens. The results indicated that HVT replicated in the FFE and in the epidermis of the skin. However, attempts to localise the site(s) of MDV replication by electron microscopy were unsuccessful."}
{"id": "PMID:228372", "title": "Cyclic AMP-induced changes in the electroencephalogram and in behavior during morphine dependence and abstinence in the rat.", "content": "Rats were prepared with permanent electrodes for recording activities of the electroencephalogram (EEG) and electromyogram (EMG) and made morphine dependent by the subcutaneous implantation of two morphine pellets. Abstinence was then precipitated by removal of the pellets 72 hr later. During the first 2 days after pellet implantation, high voltage slow activity appeared in the EEG during behavioral wakefulness and stupor, and sleep and REM sleep were greatly reduced. By the third day, tolerance to these effects developed. After pellet removal, REM sleep time during the first day was reduced. Wet dog shake activity reached a maximum during the second day of abstinence. Treatment of rats with cyclic adenosine 3',5'-monophosphate (cAMP), 50 mg/kg intraperitoneally once daily prior to and during induction of morphine dependence and during withdrawal, markedly reduced the appearance of morphine-induced high voltage EEG slow activity after implantation of the morphine pellets. Behavioral arousal during the first 2 days after pellet implantation, on the other hand, was increased. After removal of the morphine pellets, sleep episodes occurred less frequently during the first day than in the control rats. The incidence of wet shakes at this time was also elevated. These results provide direct evidence for an involvement of brain cAMP in the mediation of the central effects of morphine.", "contents": "Cyclic AMP-induced changes in the electroencephalogram and in behavior during morphine dependence and abstinence in the rat. Rats were prepared with permanent electrodes for recording activities of the electroencephalogram (EEG) and electromyogram (EMG) and made morphine dependent by the subcutaneous implantation of two morphine pellets. Abstinence was then precipitated by removal of the pellets 72 hr later. During the first 2 days after pellet implantation, high voltage slow activity appeared in the EEG during behavioral wakefulness and stupor, and sleep and REM sleep were greatly reduced. By the third day, tolerance to these effects developed. After pellet removal, REM sleep time during the first day was reduced. Wet dog shake activity reached a maximum during the second day of abstinence. Treatment of rats with cyclic adenosine 3',5'-monophosphate (cAMP), 50 mg/kg intraperitoneally once daily prior to and during induction of morphine dependence and during withdrawal, markedly reduced the appearance of morphine-induced high voltage EEG slow activity after implantation of the morphine pellets. Behavioral arousal during the first 2 days after pellet implantation, on the other hand, was increased. After removal of the morphine pellets, sleep episodes occurred less frequently during the first day than in the control rats. The incidence of wet shakes at this time was also elevated. These results provide direct evidence for an involvement of brain cAMP in the mediation of the central effects of morphine."}
{"id": "PMID:228373", "title": "Auditory arousal thresholds of good sleepers and poor sleepers with and without flurazepam.", "content": "Auditory arousal thresholds of good (N = 12) and poor (N = 12) sleepers (sleep onset insomniacs) were obtained during stage 2, stage 4, and REM sleep at various times of the night. Despite claims of being \"light\" sleepers who are easily awakened by noise, poor sleeper auditory arousal thresholds were the same as those of good sleepers. Flurazepam (30 mg) increased the auditory arousal thresholds of poor sleepers (N = 6), but the increase was statistically significant only during the period of peak effect which occurred 1--2 hr after ingestion. Consistent with poor sleeper complaints of trouble falling asleep, the return to sleep (i.e., sleep latency) was significantly longer for poor than for good sleepers following stimulus arousals during the first stage 2 and first stage 4 periods of the night. Sleep latencies for good and poor sleepers did not differ significantly following subsequent arousals. The sleep latency following the first stage 2 stimulus arousal was significantly reduced in poor sleepers during flurazepam-induced sleep.", "contents": "Auditory arousal thresholds of good sleepers and poor sleepers with and without flurazepam. Auditory arousal thresholds of good (N = 12) and poor (N = 12) sleepers (sleep onset insomniacs) were obtained during stage 2, stage 4, and REM sleep at various times of the night. Despite claims of being \"light\" sleepers who are easily awakened by noise, poor sleeper auditory arousal thresholds were the same as those of good sleepers. Flurazepam (30 mg) increased the auditory arousal thresholds of poor sleepers (N = 6), but the increase was statistically significant only during the period of peak effect which occurred 1--2 hr after ingestion. Consistent with poor sleeper complaints of trouble falling asleep, the return to sleep (i.e., sleep latency) was significantly longer for poor than for good sleepers following stimulus arousals during the first stage 2 and first stage 4 periods of the night. Sleep latencies for good and poor sleepers did not differ significantly following subsequent arousals. The sleep latency following the first stage 2 stimulus arousal was significantly reduced in poor sleepers during flurazepam-induced sleep."}
{"id": "PMID:228374", "title": "Effects of a short light-dark cycle on the sleep-wake patterns of the cat.", "content": "The purpose of this study was to measure the effect of a short, 106 min, light-dark (LD) cycle on the sleep-wake (SW) patterns of the cat. Eight cats prepared for chronic sleep studies were observed with electrographic tracings for 48 hr on a regular 12:12 hr LD schedule and again after 2 weeks of adaptation to a 27 min light and 79 min dark schedule. Each 1 min of data was scored as either alert, drowsy, slow wave sleep (SWS) or REM sleep. The parameters studied were percent electrographic state, state epoch length, polycyclic SW cycle, and mean vigilance. The short LD cycle caused a significant increase in alert state accompanied by reductions in drowsy, SWS, and REM sleep states. Although the effect was more pronounced during lights-on intervals, the trend was also present in dark intervals. Alert episodes of about all lengths increased. There were decreases in longer episodes of the other three states and a tendency for shorter episodes to increase in number. Episodes of the polycyclic SW cycle did not tend to follow the short LD cycle. The mean length of both sleep and wake episodes increased rather than decreased. However, mean vigilance values increased toward wakefulness at or near the light interval. Analyses showed that both the amplitude and phase relationship of this increase was significantly related to the 27 min light interval in comparison to base-line data. It was hypothesized that both light-dark and dark-light transitions represent alerting cues to the cat. Differences between the SW response of the cat and the rat to LD cycles are discussed.", "contents": "Effects of a short light-dark cycle on the sleep-wake patterns of the cat. The purpose of this study was to measure the effect of a short, 106 min, light-dark (LD) cycle on the sleep-wake (SW) patterns of the cat. Eight cats prepared for chronic sleep studies were observed with electrographic tracings for 48 hr on a regular 12:12 hr LD schedule and again after 2 weeks of adaptation to a 27 min light and 79 min dark schedule. Each 1 min of data was scored as either alert, drowsy, slow wave sleep (SWS) or REM sleep. The parameters studied were percent electrographic state, state epoch length, polycyclic SW cycle, and mean vigilance. The short LD cycle caused a significant increase in alert state accompanied by reductions in drowsy, SWS, and REM sleep states. Although the effect was more pronounced during lights-on intervals, the trend was also present in dark intervals. Alert episodes of about all lengths increased. There were decreases in longer episodes of the other three states and a tendency for shorter episodes to increase in number. Episodes of the polycyclic SW cycle did not tend to follow the short LD cycle. The mean length of both sleep and wake episodes increased rather than decreased. However, mean vigilance values increased toward wakefulness at or near the light interval. Analyses showed that both the amplitude and phase relationship of this increase was significantly related to the 27 min light interval in comparison to base-line data. It was hypothesized that both light-dark and dark-light transitions represent alerting cues to the cat. Differences between the SW response of the cat and the rat to LD cycles are discussed."}
{"id": "PMID:228376", "title": "Automated measurement of alpha, beta, sigma, and theta burst characteristics.", "content": "An automatic system was used for the selection and analysis of alpha, beta, and theta waveforms occurring in the awake and REM sleep states and sleep spindles occurring in stage 2 sleep. Two nights of sleep were analyzed for each of five normal subjects in each of five age groups: 3--5; 13; 25--34; 43--53; and 67--79 years of age. The waveform frequencies, length, and rate of occurrence were measured. No age-related changes were found in the alpha frequency (except for the younger group). No significant age differences were found in the beta and theta frequencies in the awake state. During REM sleep, the average beta and theta frequencies of the two youngest groups were significantly different from those of the three older groups. The average frequency of stage 2 sleep spindles of the two youngest groups was less than that in the middle group; the average spindle frequency of this group was significantly less than that of the two older groups. The number of spindles per minute was significantly less for the younger group and significantly more for the 25- to 34-year-olds.", "contents": "Automated measurement of alpha, beta, sigma, and theta burst characteristics. An automatic system was used for the selection and analysis of alpha, beta, and theta waveforms occurring in the awake and REM sleep states and sleep spindles occurring in stage 2 sleep. Two nights of sleep were analyzed for each of five normal subjects in each of five age groups: 3--5; 13; 25--34; 43--53; and 67--79 years of age. The waveform frequencies, length, and rate of occurrence were measured. No age-related changes were found in the alpha frequency (except for the younger group). No significant age differences were found in the beta and theta frequencies in the awake state. During REM sleep, the average beta and theta frequencies of the two youngest groups were significantly different from those of the three older groups. The average frequency of stage 2 sleep spindles of the two youngest groups was less than that in the middle group; the average spindle frequency of this group was significantly less than that of the two older groups. The number of spindles per minute was significantly less for the younger group and significantly more for the 25- to 34-year-olds."}
{"id": "PMID:228377", "title": "A method for transition smoothing of sleep--waking states.", "content": "A method was developed for sequential redistribution of short-duration sleep--waking states into the long-duration behavioral state(s) that surrounds these intervals. This methodological approach is useful in determination of general sleep--waking patterns such as state durations, interstate intervals, and sleep--waking cycles. The redistribution sequences had no effect on total amount of sleep or waking categories, but did decrease stage 1 with successive redistribution steps. Examination of the slope of the curve (number of occurrences or mean epoch duration divided by successive redistributions) can be used to determine the appropriate \"smoothing\" for electroencephalogram (EEG) state data via location of the breakpoint in the curve. The low-pass redistribution technique has been particularly useful for smoothing large volumes of EEG state data for subsequent analyses without significantly changing the various sleep-waking states.", "contents": "A method for transition smoothing of sleep--waking states. A method was developed for sequential redistribution of short-duration sleep--waking states into the long-duration behavioral state(s) that surrounds these intervals. This methodological approach is useful in determination of general sleep--waking patterns such as state durations, interstate intervals, and sleep--waking cycles. The redistribution sequences had no effect on total amount of sleep or waking categories, but did decrease stage 1 with successive redistribution steps. Examination of the slope of the curve (number of occurrences or mean epoch duration divided by successive redistributions) can be used to determine the appropriate \"smoothing\" for electroencephalogram (EEG) state data via location of the breakpoint in the curve. The low-pass redistribution technique has been particularly useful for smoothing large volumes of EEG state data for subsequent analyses without significantly changing the various sleep-waking states."}
{"id": "PMID:228378", "title": "Adenosine-adenosine deaminase modulation of histamine release from human basophils in vitro.", "content": "Since extracellular adenosine is a physiologically important regulator of adenylate cyclase and cell function in various mammalian tissues, we have examined the effect of adenosine on histamine release from human basophils. Adenosine inhibited IgE-mediated histamine release by its ability to increase leukocyte cyclic AMP levels; the same concentrations of adenosine which inhibited histamine release increased the cyclic AMP level of mixed leukocytes. Inhibition of histamine release was also observed with an adenosine deaminase (ADA) inhibitor [erythro-9-(2-hydroxy-3-nonyl)-adenine: EHNA] in the presence of autologous serum. We suggest that the adenosine-ADA system normally modulates histamine release and that this contributes to the severe combined immune deficiency (SCID) associated with a lack of ADA.", "contents": "Adenosine-adenosine deaminase modulation of histamine release from human basophils in vitro. Since extracellular adenosine is a physiologically important regulator of adenylate cyclase and cell function in various mammalian tissues, we have examined the effect of adenosine on histamine release from human basophils. Adenosine inhibited IgE-mediated histamine release by its ability to increase leukocyte cyclic AMP levels; the same concentrations of adenosine which inhibited histamine release increased the cyclic AMP level of mixed leukocytes. Inhibition of histamine release was also observed with an adenosine deaminase (ADA) inhibitor [erythro-9-(2-hydroxy-3-nonyl)-adenine: EHNA] in the presence of autologous serum. We suggest that the adenosine-ADA system normally modulates histamine release and that this contributes to the severe combined immune deficiency (SCID) associated with a lack of ADA."}
{"id": "PMID:228387", "title": "Serum lipoproteins in children with anaemia.", "content": "Plasma and erythrocyte lipids were estimated in 9 children with different types of anaemia and in 9 healthy control children. The anaemic children had rather high plasma triglcerides, but low total cholesterol and phospholipids. The levels of high density lipoprotein (HDL) cholesterol were particularly low, with a mean of only 70% of the controls. A positive correlation was found for haematocrit with HDL cholesterol, but not with low density lipoprotein (LDL) cholesterol. Plasma albumin was at the same level in both groups of children, however, suggesting that the diluting effect of increase in plasma volume could only partly explain the lowering of HDL cholesterol. A striking, inverse correlation between HDL cholesterol and very low density lipoprotein (VLDL) triglycerides was present in the anaemic children. Anaemia in children adds to previously recognized pathophysiological condditions which induce inversely interrelated changes in HDL and VLDL.", "contents": "Serum lipoproteins in children with anaemia. Plasma and erythrocyte lipids were estimated in 9 children with different types of anaemia and in 9 healthy control children. The anaemic children had rather high plasma triglcerides, but low total cholesterol and phospholipids. The levels of high density lipoprotein (HDL) cholesterol were particularly low, with a mean of only 70% of the controls. A positive correlation was found for haematocrit with HDL cholesterol, but not with low density lipoprotein (LDL) cholesterol. Plasma albumin was at the same level in both groups of children, however, suggesting that the diluting effect of increase in plasma volume could only partly explain the lowering of HDL cholesterol. A striking, inverse correlation between HDL cholesterol and very low density lipoprotein (VLDL) triglycerides was present in the anaemic children. Anaemia in children adds to previously recognized pathophysiological condditions which induce inversely interrelated changes in HDL and VLDL."}
{"id": "PMID:228383", "title": "[Phosphoribosylpyrophosphate synthetase anomalies in 2 cases of gout beginning at an early age].", "content": "On the basis of a study of the action of phosphoribosylpyrophosphate (PRPP) synthetase (EC 2.7.6.1.) in 22 hyperuricemic and 9 normal subjects, the authors report two cases of gout with anomalies of the kinetics of this enzyme. The anomaly consists of an increase in affinity for inorganic phosphate (iP) in the absence of inhibitors, and a decrease in inhibition by low concentrations of ADP in the presence of iP. These patients show no other anomaly of intraerythrocyte PRPP (dosage and production \"in vitro\"), hypoxanthine-guanine-phosphoribosyl-transferase and APRTase (overall activity and apparent Km). These two cases of gout are characterized clinically by their early occurrence, appearing in one case in a pre-menopausal woman, their family character and their normal sensitivity to allopurinol.", "contents": "[Phosphoribosylpyrophosphate synthetase anomalies in 2 cases of gout beginning at an early age]. On the basis of a study of the action of phosphoribosylpyrophosphate (PRPP) synthetase (EC 2.7.6.1.) in 22 hyperuricemic and 9 normal subjects, the authors report two cases of gout with anomalies of the kinetics of this enzyme. The anomaly consists of an increase in affinity for inorganic phosphate (iP) in the absence of inhibitors, and a decrease in inhibition by low concentrations of ADP in the presence of iP. These patients show no other anomaly of intraerythrocyte PRPP (dosage and production \"in vitro\"), hypoxanthine-guanine-phosphoribosyl-transferase and APRTase (overall activity and apparent Km). These two cases of gout are characterized clinically by their early occurrence, appearing in one case in a pre-menopausal woman, their family character and their normal sensitivity to allopurinol."}
{"id": "PMID:228388", "title": "Altered erythrocyte membrane protein phosphorylation in an unusual case of hereditary spherocytosis.", "content": "Membrane protein phosphorylation was examined in several members from a family with an unusual form of hereditary sperocytosis. After incubation of membrane ghosts with (gamma-32 P) ATP, the phosphorylation of spectrin component II was diminished both in the absence of cAMP. In the presence of this nucleotide, the phosphorylation of components IV5 and IV8 was also decreased. Along with a previously reported alteration of a membrane neutral phosphatase in this family, these abnormalities remove the present condition from the usual form of hereditary spherocytosis.", "contents": "Altered erythrocyte membrane protein phosphorylation in an unusual case of hereditary spherocytosis. Membrane protein phosphorylation was examined in several members from a family with an unusual form of hereditary sperocytosis. After incubation of membrane ghosts with (gamma-32 P) ATP, the phosphorylation of spectrin component II was diminished both in the absence of cAMP. In the presence of this nucleotide, the phosphorylation of components IV5 and IV8 was also decreased. Along with a previously reported alteration of a membrane neutral phosphatase in this family, these abnormalities remove the present condition from the usual form of hereditary spherocytosis."}
{"id": "PMID:228391", "title": "BK virus DNA: complete nucleotide sequence of a human tumor virus.", "content": "The complete DNA sequence of the human papovavirus BK is presented. From the 4963 base-pair sequence of BK virus (MM strain), the amino acid sequence of at least five proteins can be deduced: a T antigen and a t antigen, which share amino terminal peptides; proteins VP2 and VP3, which share 232 amino acids; and protein VP1, whose coding sequence overlaps those for VP2 and VP3 by 113 nucleotides but is read in a different frame. The gene loci and the arrangement of genes are strikingly similar in BK virus and simian virus 40 (SV40). The sequence of the deduced proteins in BK virus shares 73 percent amino acid homology with those in SV40, whereas the DNA sequence of the two viruses shares 70 percent homology, suggesting close evolutionary relationship. However, the repeated DNA sequences in the noncoding regions of these viruses are different.", "contents": "BK virus DNA: complete nucleotide sequence of a human tumor virus. The complete DNA sequence of the human papovavirus BK is presented. From the 4963 base-pair sequence of BK virus (MM strain), the amino acid sequence of at least five proteins can be deduced: a T antigen and a t antigen, which share amino terminal peptides; proteins VP2 and VP3, which share 232 amino acids; and protein VP1, whose coding sequence overlaps those for VP2 and VP3 by 113 nucleotides but is read in a different frame. The gene loci and the arrangement of genes are strikingly similar in BK virus and simian virus 40 (SV40). The sequence of the deduced proteins in BK virus shares 73 percent amino acid homology with those in SV40, whereas the DNA sequence of the two viruses shares 70 percent homology, suggesting close evolutionary relationship. However, the repeated DNA sequences in the noncoding regions of these viruses are different."}
{"id": "PMID:228392", "title": "Intrathecal capsaicin depletes substance P in the rat spinal cord and produces prolonged thermal analgesia.", "content": "A single intrathecal injection of capsaicin depletes substance P from primary sensory neurons and causes a prolonged increase in the thermal and chemical pain thresholds of the rat but no apparent change in responses to noxious mechanical stimuli.", "contents": "Intrathecal capsaicin depletes substance P in the rat spinal cord and produces prolonged thermal analgesia. A single intrathecal injection of capsaicin depletes substance P from primary sensory neurons and causes a prolonged increase in the thermal and chemical pain thresholds of the rat but no apparent change in responses to noxious mechanical stimuli."}
{"id": "PMID:228394", "title": "The dielectric constant of phospholipid bilayers and the permeability of membranes to ions.", "content": "The Born charging equation predicts that the permeability of a phospholipid bilayer membrane to ions should depend markedly on the dielectric constant of the membrane. Increasing the dielectric constant of an artificial bilayer increases its permeability to perchlorate or thiocyanate by a factor of 1000, to a value comparable to that of mitochondrial membranes.", "contents": "The dielectric constant of phospholipid bilayers and the permeability of membranes to ions. The Born charging equation predicts that the permeability of a phospholipid bilayer membrane to ions should depend markedly on the dielectric constant of the membrane. Increasing the dielectric constant of an artificial bilayer increases its permeability to perchlorate or thiocyanate by a factor of 1000, to a value comparable to that of mitochondrial membranes."}
{"id": "PMID:228395", "title": "Generation by insulin of a chemical mediator that controls protein phosphorylation and dephosphorylation.", "content": "Deproteinized skeletal muscle extracts free of major nucleotides from control and insulin-treated rats were fractionated and assayed for inhibition of protein phosphorylation by cyclic adenosine monophosphate (AMP)-dependent and -independent protein kinases. A differential effect of insulin on a particular fraction was observed on cyclic AMP-dependent protein kinase but not on cyclic AMP-independent protein kinases. This fraction that inhibited cyclic AMP-dependent protein kinase also stimulated glycogen synthase phosphoprotein phosphatase. It is proposed that this fraction may contain a mediator substance generateed in the presence of insulin.", "contents": "Generation by insulin of a chemical mediator that controls protein phosphorylation and dephosphorylation. Deproteinized skeletal muscle extracts free of major nucleotides from control and insulin-treated rats were fractionated and assayed for inhibition of protein phosphorylation by cyclic adenosine monophosphate (AMP)-dependent and -independent protein kinases. A differential effect of insulin on a particular fraction was observed on cyclic AMP-dependent protein kinase but not on cyclic AMP-independent protein kinases. This fraction that inhibited cyclic AMP-dependent protein kinase also stimulated glycogen synthase phosphoprotein phosphatase. It is proposed that this fraction may contain a mediator substance generateed in the presence of insulin."}
{"id": "PMID:228398", "title": "[Renal lesions in myelofibrosis (author's transl)].", "content": "In 26 cases of myelofibrosis, the authors investigated for possible renal impairment that can be appraised from the usual clinical, laboratory, and roentgenographic signs. No anomalies were demonstrated in 12 of these cases. In 14 (or 53%) of the patients, some anomaly was discovered : essentially proteinuria with minor alteration of renal function, but also, two cases of poorly functioning left kidney evidenced on intravenous urograms, one case of acute anuric renal failure connected with hyperuricemia, one case of hypokalemic tubulo-interstitial nephritis, and one case of glomerulonephritis with, nephrotic syndrome. This study, when compared to the literature, indicates that besides nephropathy specific to myelofibrosis and attributed to myeloid metaplasia in the kidney, serious consideration must be given to lesions due to (1) compression of the left kidney by the enlarged spleen, (2) urate precipitation in the urinary passages, and (3) a possible glomerular disorder whose mechanism remains undefined.", "contents": "[Renal lesions in myelofibrosis (author's transl)]. In 26 cases of myelofibrosis, the authors investigated for possible renal impairment that can be appraised from the usual clinical, laboratory, and roentgenographic signs. No anomalies were demonstrated in 12 of these cases. In 14 (or 53%) of the patients, some anomaly was discovered : essentially proteinuria with minor alteration of renal function, but also, two cases of poorly functioning left kidney evidenced on intravenous urograms, one case of acute anuric renal failure connected with hyperuricemia, one case of hypokalemic tubulo-interstitial nephritis, and one case of glomerulonephritis with, nephrotic syndrome. This study, when compared to the literature, indicates that besides nephropathy specific to myelofibrosis and attributed to myeloid metaplasia in the kidney, serious consideration must be given to lesions due to (1) compression of the left kidney by the enlarged spleen, (2) urate precipitation in the urinary passages, and (3) a possible glomerular disorder whose mechanism remains undefined."}
{"id": "PMID:228399", "title": "[Renal oncocytomas (author's transl)].", "content": "The authors report their experience of a rare tumor of kidney : oncocytoma. This tumor was made of polygonal cells separated by an endocrinoid stroma. They report pathological feature and clinical course and pronostic who is better than in carcinoma. Other names have been given : proximal tubular adenomas, true kidney hypernephroma, Riopelle tumor.", "contents": "[Renal oncocytomas (author's transl)]. The authors report their experience of a rare tumor of kidney : oncocytoma. This tumor was made of polygonal cells separated by an endocrinoid stroma. They report pathological feature and clinical course and pronostic who is better than in carcinoma. Other names have been given : proximal tubular adenomas, true kidney hypernephroma, Riopelle tumor."}
{"id": "PMID:228396", "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:228400", "title": "[Secondary effects of Dimer X radiculography after premedication. A study of hundred patients (author's transl)].", "content": "The authors describe side effects of Dimer X radiculography after premedication. The side effects in a study of hundred patients are divided in early complications (during the examination : dizziness, radicular pains and collapse) and in late complications (noted during the first day following the examination : headache, meningismus, myocloni, epileptic seizure, cauda syndrome, increase of radicular pains). After premedication with tiapride the rate of dizziness is decreased, the rate of headache is not diminished, but the headaches are very slight. Nausea and vomiting are suppressed by the premedication.", "contents": "[Secondary effects of Dimer X radiculography after premedication. A study of hundred patients (author's transl)]. The authors describe side effects of Dimer X radiculography after premedication. The side effects in a study of hundred patients are divided in early complications (during the examination : dizziness, radicular pains and collapse) and in late complications (noted during the first day following the examination : headache, meningismus, myocloni, epileptic seizure, cauda syndrome, increase of radicular pains). After premedication with tiapride the rate of dizziness is decreased, the rate of headache is not diminished, but the headaches are very slight. Nausea and vomiting are suppressed by the premedication."}
{"id": "PMID:228397", "title": "[Chemotherapy of multiple bone myeloma. Prognostic features and response criteria (First part) (author's transl)].", "content": "The authors reviewed the recent data about prognostic factors, criteria of response and chemotherapy in multiple myeloma of bone. They insist on the new staging of durie and salmon and on the interest of polychemotherapy.", "contents": "[Chemotherapy of multiple bone myeloma. Prognostic features and response criteria (First part) (author's transl)]. The authors reviewed the recent data about prognostic factors, criteria of response and chemotherapy in multiple myeloma of bone. They insist on the new staging of durie and salmon and on the interest of polychemotherapy."}
{"id": "PMID:228402", "title": "[Decrease of the erythrocyte filterability and cerebrovascular accidents. Study in eighty patients (author's transl)].", "content": "Erythrocyte filterability has been studied in 80 patients (44 men and 36 women) with recent stroke (mean age of patients was 68). 200 adults were studied as reference. The filtration time is significantly higher in patients than in normal subjects (p less than 0,001). High individual variations are found in patients, in relation with the presence of cardiovascular risk factors. In conclusion, the role of erythrocyte deformability in cerebrovascular disease is discussed.", "contents": "[Decrease of the erythrocyte filterability and cerebrovascular accidents. Study in eighty patients (author's transl)]. Erythrocyte filterability has been studied in 80 patients (44 men and 36 women) with recent stroke (mean age of patients was 68). 200 adults were studied as reference. The filtration time is significantly higher in patients than in normal subjects (p less than 0,001). High individual variations are found in patients, in relation with the presence of cardiovascular risk factors. In conclusion, the role of erythrocyte deformability in cerebrovascular disease is discussed."}
{"id": "PMID:228401", "title": "[Acute abdominal syndromes and anisakiasis. A new case (author's transl)].", "content": "To the list of the well known parasitic diseases which are expressed by acute abdominal syndromes and which need laparotomy, we may now add the anisakiasis. At the end of a complex cycle, the ingestion of herring can infected man : frequently the parasite is fixed at the level of the stomach, or of the ileum and seldom at the level of the bowel. Its presence gives rise to pain, hemorragy, tumor or occlusion in relation with the parietal granuloma. From one personal case the authors analyse the originality of this parasitic disease, the difficulty of its diagnosis before surgical time and its good prognosis.", "contents": "[Acute abdominal syndromes and anisakiasis. A new case (author's transl)]. To the list of the well known parasitic diseases which are expressed by acute abdominal syndromes and which need laparotomy, we may now add the anisakiasis. At the end of a complex cycle, the ingestion of herring can infected man : frequently the parasite is fixed at the level of the stomach, or of the ileum and seldom at the level of the bowel. Its presence gives rise to pain, hemorragy, tumor or occlusion in relation with the parietal granuloma. From one personal case the authors analyse the originality of this parasitic disease, the difficulty of its diagnosis before surgical time and its good prognosis."}
{"id": "PMID:228403", "title": "[Cystic dystrophy of the urinary tract excretory mucosa. A report of six new cases (author's transl)].", "content": "The authors report 6 cases of kystic dystrophy of the upper urinary tract. A review of the literature and the discussion of the described cases leads to some comments about the pathogeny, the diagnosis and the treatment of this poorly defined syndrome which is due to injuries to the mucosae under the influence of phenomenous more probably inflammatory than vascular.", "contents": "[Cystic dystrophy of the urinary tract excretory mucosa. A report of six new cases (author's transl)]. The authors report 6 cases of kystic dystrophy of the upper urinary tract. A review of the literature and the discussion of the described cases leads to some comments about the pathogeny, the diagnosis and the treatment of this poorly defined syndrome which is due to injuries to the mucosae under the influence of phenomenous more probably inflammatory than vascular."}
{"id": "PMID:228404", "title": "[Gall-bladder troubles and oral contraceptives (author's transl)].", "content": "On the basis of about one hundred and fifty cases, the authors study the effect of oral contraceptives on the gall-bladder. After having showed their results, they discuss the mechanism of the action of oral contraceptives on the gall-bladder, showing their favouring effect on gallstones and pointing out the delay in gall-bladder emptying induced by them.", "contents": "[Gall-bladder troubles and oral contraceptives (author's transl)]. On the basis of about one hundred and fifty cases, the authors study the effect of oral contraceptives on the gall-bladder. After having showed their results, they discuss the mechanism of the action of oral contraceptives on the gall-bladder, showing their favouring effect on gallstones and pointing out the delay in gall-bladder emptying induced by them."}
{"id": "PMID:228405", "title": "[A new therapeutic approach of associated metabolic diseases. 1 000 patients treated with benfluorex (author's transl)].", "content": "Multiple metabolic factors of atherosclerosis frequently associated in the same patient proves the interest of a multifactorial treatment of atherosclerosis. In the paper the authors studied the results of the treatment with benfluorex of 1 000 patients suffering one or more metabolic risk factors. After a 3 month treatment, a highly significant and simultaneous reduction of hyperlipidemia, hyperglycemia, hyperuricemia is observed. The treatment is the more efficient that initial values are higher and that the diet is better observed. The results remain significant even in patients who have not lost weight.", "contents": "[A new therapeutic approach of associated metabolic diseases. 1 000 patients treated with benfluorex (author's transl)]. Multiple metabolic factors of atherosclerosis frequently associated in the same patient proves the interest of a multifactorial treatment of atherosclerosis. In the paper the authors studied the results of the treatment with benfluorex of 1 000 patients suffering one or more metabolic risk factors. After a 3 month treatment, a highly significant and simultaneous reduction of hyperlipidemia, hyperglycemia, hyperuricemia is observed. The treatment is the more efficient that initial values are higher and that the diet is better observed. The results remain significant even in patients who have not lost weight."}
{"id": "PMID:228407", "title": "[Small intestine intubation during operative treatment of primary or recurring intestinal obstructions (author's transl)].", "content": "The author reports eight cases of recurrent obstruction treated by intubation of the small bowel. This technic, possible in any cases, avoids other long and often difficult technics. The tube used in those cases intends to maintain a normal circumference to the small bowel on all its length and to secure its permanent evacuation till it begins to function normally.", "contents": "[Small intestine intubation during operative treatment of primary or recurring intestinal obstructions (author's transl)]. The author reports eight cases of recurrent obstruction treated by intubation of the small bowel. This technic, possible in any cases, avoids other long and often difficult technics. The tube used in those cases intends to maintain a normal circumference to the small bowel on all its length and to secure its permanent evacuation till it begins to function normally."}
{"id": "PMID:228406", "title": "[Multiple primary malignant melanomas. A report of five cases (author's transl)].", "content": "The authors present 5 cases of primary malignant melanomas occurring simuatlneously or successively, diagnosed at Institut Gustave Roussy over a period of 10 years. This work emphasizes the need for searching possible changes of nevi in melanoma patients.", "contents": "[Multiple primary malignant melanomas. A report of five cases (author's transl)]. The authors present 5 cases of primary malignant melanomas occurring simuatlneously or successively, diagnosed at Institut Gustave Roussy over a period of 10 years. This work emphasizes the need for searching possible changes of nevi in melanoma patients."}
{"id": "PMID:228408", "title": "[D-penicillamine in rheumatoid arthritis : hematological incidents and accidents (author's transl)].", "content": "From literature data and their own experience, the authors comment hematological complications, related to the use of D-penicillamine, mainly in theumato\u00efd arthritis. Hypereosinophilia is more common than thrombopenia, but, both complications are usually benign. Anemia alone is very rare. Leukopenia appears in 6% of treated patients, but pancytopenia is rare. Leukopenia and pancytopenia are the most severe complications, even fatal in some cases. The safest dose of D-penicillamine seems to be between 600 and 900 mg per day, provided that, however, regular hematological controls may be achieved.", "contents": "[D-penicillamine in rheumatoid arthritis : hematological incidents and accidents (author's transl)]. From literature data and their own experience, the authors comment hematological complications, related to the use of D-penicillamine, mainly in theumato\u00efd arthritis. Hypereosinophilia is more common than thrombopenia, but, both complications are usually benign. Anemia alone is very rare. Leukopenia appears in 6% of treated patients, but pancytopenia is rare. Leukopenia and pancytopenia are the most severe complications, even fatal in some cases. The safest dose of D-penicillamine seems to be between 600 and 900 mg per day, provided that, however, regular hematological controls may be achieved."}
{"id": "PMID:228409", "title": "[Acute nephritis and allergic vasculitis due to phenindione (author's transl)].", "content": "The authors report a case of acute nephritis which appears during a treatment with phenindione. The nephropathy described after this medication are now well known. Their manifestations are either a proteinuria associated or not with a nephrotic syndrome or an interstitial nephritis whose pronostic is reserved. In this observation the mechanism is different : the lesion is glomerular and complicates an allergic vasculitis which was secondary to the phenindione's therapy. The pronostic was good.", "contents": "[Acute nephritis and allergic vasculitis due to phenindione (author's transl)]. The authors report a case of acute nephritis which appears during a treatment with phenindione. The nephropathy described after this medication are now well known. Their manifestations are either a proteinuria associated or not with a nephrotic syndrome or an interstitial nephritis whose pronostic is reserved. In this observation the mechanism is different : the lesion is glomerular and complicates an allergic vasculitis which was secondary to the phenindione's therapy. The pronostic was good."}
{"id": "PMID:228410", "title": "[Association for ankylosing spondylarthritis multiple myeloma. A case history (author's transl)].", "content": "The authors describe a patient treated 16 years by phenylbutazone for ankylosing spondylarthritis and in whom appeared an IgA multiple myeloma with a Kappa light chain. This pathological association is rare and we can wonder about the respective etiopathological roles of spondylarthritis and its treatment by phenylbutazone in the occurrence of multiple myeloma.", "contents": "[Association for ankylosing spondylarthritis multiple myeloma. A case history (author's transl)]. The authors describe a patient treated 16 years by phenylbutazone for ankylosing spondylarthritis and in whom appeared an IgA multiple myeloma with a Kappa light chain. This pathological association is rare and we can wonder about the respective etiopathological roles of spondylarthritis and its treatment by phenylbutazone in the occurrence of multiple myeloma."}
{"id": "PMID:228411", "title": "[Two cases of traumatic rupture of the corpus cavernosum (author's transl)].", "content": "The authors report two cases of traumatic rupture of the corpus cavernosum and have insisted on the early repair of the tunica albuginea best guarantee of adequate cure without erection impairement.", "contents": "[Two cases of traumatic rupture of the corpus cavernosum (author's transl)]. The authors report two cases of traumatic rupture of the corpus cavernosum and have insisted on the early repair of the tunica albuginea best guarantee of adequate cure without erection impairement."}
{"id": "PMID:228413", "title": "[Bronchopulmonary adenocarcinomas of apparently primary origin. A retrospective study of sixty-six patients (author's transl)].", "content": "A retrospective study of sixty-six case-reports confirmed the traditional factors described in this histological type of cancer, particularly the age, a slight predominence of males, and the very poor prognosis. A selection was made of 42 cases in which extensive investigations had been carried out to search for a possible extrapulmonary primary adenocarcinoma, but only one case of renal cancer and one of thyroid cancer were demonstrated. Autopsy had revealed the presence of 3 prostatic lesions and their relation to the pulmonary affection is discussed. Thyroid cancer had been found in 2 cases, which emphasizes the value of scintigraphy for this organ, whereas the authors felt that other investigations were of no value in the absence of clinically oriented signs.", "contents": "[Bronchopulmonary adenocarcinomas of apparently primary origin. A retrospective study of sixty-six patients (author's transl)]. A retrospective study of sixty-six case-reports confirmed the traditional factors described in this histological type of cancer, particularly the age, a slight predominence of males, and the very poor prognosis. A selection was made of 42 cases in which extensive investigations had been carried out to search for a possible extrapulmonary primary adenocarcinoma, but only one case of renal cancer and one of thyroid cancer were demonstrated. Autopsy had revealed the presence of 3 prostatic lesions and their relation to the pulmonary affection is discussed. Thyroid cancer had been found in 2 cases, which emphasizes the value of scintigraphy for this organ, whereas the authors felt that other investigations were of no value in the absence of clinically oriented signs."}
{"id": "PMID:228414", "title": "[Sarcoidosis associated with tuberculosis. A study of seven patients (author's transl)].", "content": "The authors studied seven patients with sarcoidosis and tuberculosis: the affections co-existed in 3 cases but were separated by varying intervals of time in the 4 other patients. They discuss the diagnostic, therapeutic, and nosological problems posed by these cases, and review the various hypotheses that have been suggested to explain these associations in relation to the pathogenesis of the sarcoidosis.", "contents": "[Sarcoidosis associated with tuberculosis. A study of seven patients (author's transl)]. The authors studied seven patients with sarcoidosis and tuberculosis: the affections co-existed in 3 cases but were separated by varying intervals of time in the 4 other patients. They discuss the diagnostic, therapeutic, and nosological problems posed by these cases, and review the various hypotheses that have been suggested to explain these associations in relation to the pathogenesis of the sarcoidosis."}
{"id": "PMID:228412", "title": "[Complications of anticoagulant treatment. Report of 98 accidents and incidents (author's transl)].", "content": "According to an estimation on 1 587 patients under anticoagulant treatment, 84 of them have caught a therapeutic accident so a frequency of 5,3 per cent. It concerns 98 therapeutic accidents : 89 haemorrhagic spontaneous accidents (11 digestive haemorrhages, 5 cerebro-vascular accidents, 54 hematomas with 18 retro-peritoneals and 11 in musculis rectis abdominis, 9 hematuries, 2 serous haemorrhages, 8 various haemorrhages) ; 8 \"induced\" haemorrhages, in which 5 after arterial catheterism, and an accident allergic to the phenyl-indane-dione. Nine deceases were revealed : in which 5 are directly attributed to the hemorrhagic accident (3 cerebro-vascular accidents and 2 serous haemorrhages).", "contents": "[Complications of anticoagulant treatment. Report of 98 accidents and incidents (author's transl)]. According to an estimation on 1 587 patients under anticoagulant treatment, 84 of them have caught a therapeutic accident so a frequency of 5,3 per cent. It concerns 98 therapeutic accidents : 89 haemorrhagic spontaneous accidents (11 digestive haemorrhages, 5 cerebro-vascular accidents, 54 hematomas with 18 retro-peritoneals and 11 in musculis rectis abdominis, 9 hematuries, 2 serous haemorrhages, 8 various haemorrhages) ; 8 \"induced\" haemorrhages, in which 5 after arterial catheterism, and an accident allergic to the phenyl-indane-dione. Nine deceases were revealed : in which 5 are directly attributed to the hemorrhagic accident (3 cerebro-vascular accidents and 2 serous haemorrhages)."}
{"id": "PMID:228415", "title": "[Chemotherapy of multiple bone myeloma. Historical and present day aspects. (Second part) (author's transl)].", "content": "The authors reviewed the recent data about prognostic factors, criteria of response and chemotherapy in multiple myeloma of bone. They insist on the new staging of durie and salmon anf on the interest of poly chemotherapy.", "contents": "[Chemotherapy of multiple bone myeloma. Historical and present day aspects. (Second part) (author's transl)]. The authors reviewed the recent data about prognostic factors, criteria of response and chemotherapy in multiple myeloma of bone. They insist on the new staging of durie and salmon anf on the interest of poly chemotherapy."}
{"id": "PMID:228416", "title": "[Folate and the nervous system (author's transl)].", "content": "The responsibility of the folate deficiency in some neuropsychiatric disorders is recent knowledge. The role of the folate on the nervous system is not yet well definite, but the action on the metabolism of the amino-acids, on the purine and the pyrimidine synthesis and on the metabolism of the catecholamins are certainly essential. The neuropsychiatric diseases secondary to the folate deficiency are numerous: dementia, schizophrenia like syndromes, insomnia, irritability, forgetfulness, endogenous depression, organic psychosis, pueperal psychosis, peripheral neuropathy, myelopathy (spinal cord syndrome and/or pyramidal tract damage), restless legs syndrome. Clinically the diagnosis may be difficult with sub acute combined degenration secondary to the pernicious anaemia, and the dosage of the folate (in serum, in red-cells and in cerebrospinal fluid) is necessary. The congenital defects in the uptake or utilization of the folate are associated with neuropsychiatric disturbances. The treatment is easy and safe if the vitamin B12 deficiency is eliminated and if employed with caution in epileptic patients because folate can induced seizures.", "contents": "[Folate and the nervous system (author's transl)]. The responsibility of the folate deficiency in some neuropsychiatric disorders is recent knowledge. The role of the folate on the nervous system is not yet well definite, but the action on the metabolism of the amino-acids, on the purine and the pyrimidine synthesis and on the metabolism of the catecholamins are certainly essential. The neuropsychiatric diseases secondary to the folate deficiency are numerous: dementia, schizophrenia like syndromes, insomnia, irritability, forgetfulness, endogenous depression, organic psychosis, pueperal psychosis, peripheral neuropathy, myelopathy (spinal cord syndrome and/or pyramidal tract damage), restless legs syndrome. Clinically the diagnosis may be difficult with sub acute combined degenration secondary to the pernicious anaemia, and the dosage of the folate (in serum, in red-cells and in cerebrospinal fluid) is necessary. The congenital defects in the uptake or utilization of the folate are associated with neuropsychiatric disturbances. The treatment is easy and safe if the vitamin B12 deficiency is eliminated and if employed with caution in epileptic patients because folate can induced seizures."}
{"id": "PMID:228417", "title": "[Alexia without agraphia, colour \"agnosia\" and right visual field defect: a syndrome of the posterior cerebral artery (author's transl)].", "content": "Two cases of alexia without agraphia are reported, with differences in the characters of the alexia and in the accompanying signs. The visual field defect was limited to quadranopia in both cases which was upper quadrantic and mild in one, lower quadrantic and severe in the other. These differences make it unlikely that a similar anatomical location of the lesion and a unique mechanism are responsible of all cases of alexia without agraphia. Persistance of visual inputs in the right visual field is partial in our cases, but alexia without hemianopsia does exist. These facts are against the mechanism of \"splenio-cortical\" disconnection proposed by Geschwind as the only explanation. A \"cortical\", or agnosic mechanism has been also claimed, with lesions of the lingual and fusiform gyri on the dominant side, as well as \"subangular\", mechanism, with intrahemispheric disconnection by a lesion located between the visual associative areas and the angular gyrus: in these last two situations an hemianopsia is not necessarily associated to the alexia without agraphia.", "contents": "[Alexia without agraphia, colour \"agnosia\" and right visual field defect: a syndrome of the posterior cerebral artery (author's transl)]. Two cases of alexia without agraphia are reported, with differences in the characters of the alexia and in the accompanying signs. The visual field defect was limited to quadranopia in both cases which was upper quadrantic and mild in one, lower quadrantic and severe in the other. These differences make it unlikely that a similar anatomical location of the lesion and a unique mechanism are responsible of all cases of alexia without agraphia. Persistance of visual inputs in the right visual field is partial in our cases, but alexia without hemianopsia does exist. These facts are against the mechanism of \"splenio-cortical\" disconnection proposed by Geschwind as the only explanation. A \"cortical\", or agnosic mechanism has been also claimed, with lesions of the lingual and fusiform gyri on the dominant side, as well as \"subangular\", mechanism, with intrahemispheric disconnection by a lesion located between the visual associative areas and the angular gyrus: in these last two situations an hemianopsia is not necessarily associated to the alexia without agraphia."}
{"id": "PMID:228418", "title": "[About 2 cases of \"dry syndrome\" associating xerophthalmy, xerostomy and cutaneous dryness. A new entity or an unrecognized diagnostic? (author's transl)].", "content": "Two cases, in children of distinct families, of a particular form of \"dry syndrome\", are described. This syndrom, which associates xerophthalmy, xerostomy and cutaneous dryness, is congenital and familial. He looks different from previously described diseases or syndroms which include one or several of these three components.", "contents": "[About 2 cases of \"dry syndrome\" associating xerophthalmy, xerostomy and cutaneous dryness. A new entity or an unrecognized diagnostic? (author's transl)]. Two cases, in children of distinct families, of a particular form of \"dry syndrome\", are described. This syndrom, which associates xerophthalmy, xerostomy and cutaneous dryness, is congenital and familial. He looks different from previously described diseases or syndroms which include one or several of these three components."}
{"id": "PMID:228419", "title": "[A clinical study in neurosurgical diseases. A report on eighty cases (author's transl)].", "content": "The authors describe 80 patients with neurosurgical disorders treated with tiapride, either during neurosurgical investigations including radiological examinations after removal of cerebrospinal fluid, or for agitation following alcoholism or meningeal haemorrhage. The authors stress the value of tiapride for patients undergoing radiculography and especially gas myelography procedures. The effect of tiapride on the various manifestations of agitation was also spectacular and rapid, and the authors confirm the excellent tolerance of the product.", "contents": "[A clinical study in neurosurgical diseases. A report on eighty cases (author's transl)]. The authors describe 80 patients with neurosurgical disorders treated with tiapride, either during neurosurgical investigations including radiological examinations after removal of cerebrospinal fluid, or for agitation following alcoholism or meningeal haemorrhage. The authors stress the value of tiapride for patients undergoing radiculography and especially gas myelography procedures. The effect of tiapride on the various manifestations of agitation was also spectacular and rapid, and the authors confirm the excellent tolerance of the product."}
{"id": "PMID:228421", "title": "[Sexual transmissible diseases (author's transl)].", "content": "Following a paper in the issue of the Annales d'Urologie of September 1978, the author recalls some of other essential present facts, in diagnosis and treatments of sexual transmissibles diseases (STD) : importance of clinical examination ; a few pecularities of bacteriology ; problems of suffering patients (urethra or prostate), without injury nor infection ; what must be avoided ,and what behaviour must be adopted ; epidemiological problems caused by general present sexual behaviour.", "contents": "[Sexual transmissible diseases (author's transl)]. Following a paper in the issue of the Annales d'Urologie of September 1978, the author recalls some of other essential present facts, in diagnosis and treatments of sexual transmissibles diseases (STD) : importance of clinical examination ; a few pecularities of bacteriology ; problems of suffering patients (urethra or prostate), without injury nor infection ; what must be avoided ,and what behaviour must be adopted ; epidemiological problems caused by general present sexual behaviour."}
{"id": "PMID:228420", "title": "[Two cases of gluten intolerance presenting as dwarfism (author's transl)].", "content": "Two patients with dwarfism were found to have intolerance to gluten. The authors describe the clinical, biological and radiological signs which enable the growth disorder to be related to its true cause, when obvious signs of a celiac syndrome are lacking. In fact, a small intestine biopsy is the essential diagnostic procedure. The hormonal changes found in such patients are discussed, and include normal HGH levels, reduced somatomedin activity which becomes normal after a gluten-free diet, and low blood insulin levels in the basal state as in insulin tolerance tests.", "contents": "[Two cases of gluten intolerance presenting as dwarfism (author's transl)]. Two patients with dwarfism were found to have intolerance to gluten. The authors describe the clinical, biological and radiological signs which enable the growth disorder to be related to its true cause, when obvious signs of a celiac syndrome are lacking. In fact, a small intestine biopsy is the essential diagnostic procedure. The hormonal changes found in such patients are discussed, and include normal HGH levels, reduced somatomedin activity which becomes normal after a gluten-free diet, and low blood insulin levels in the basal state as in insulin tolerance tests."}
{"id": "PMID:228422", "title": "[Homogeneity of the erythrocyte volume distribution during chronic alcoholism macrocytosis (author's transl)].", "content": "The increase in volume of human erythrocytes during chronic alcoholic intoxication and its decrease after alcoholic deprivation was studied with a multichannel analyzer. When fractions of the population of red cells were separated by differential centrifugation the macrocytosis was found to be uniformly distributed. The presence of macrocytes was not related to changes of plasma osmolality or hyperhydration of red cells. A central origin was evoked, however, the role of the folic acid deficiency could not explain the macrocytosis, the mechanism of which remains to be elucidated.", "contents": "[Homogeneity of the erythrocyte volume distribution during chronic alcoholism macrocytosis (author's transl)]. The increase in volume of human erythrocytes during chronic alcoholic intoxication and its decrease after alcoholic deprivation was studied with a multichannel analyzer. When fractions of the population of red cells were separated by differential centrifugation the macrocytosis was found to be uniformly distributed. The presence of macrocytes was not related to changes of plasma osmolality or hyperhydration of red cells. A central origin was evoked, however, the role of the folic acid deficiency could not explain the macrocytosis, the mechanism of which remains to be elucidated."}
{"id": "PMID:228423", "title": "[Secondary pericarditis after myocardial infarction (author's transl)].", "content": "Our study concerns 480 observations about myocardial infarctions. In 10% of the cases, we have found a premature pericarditis diagnosed on the pericardic friction, electric and biologic signes. Some complications such as rythmical troubles, left ventricular dificiency, parietal anevrism are more frequent and increase the prognosis. In 1,2% of the cases, we find a post-infarction syndrom of Dressler, the prognosis of which is mild. The diagnosis is founded on the revival of the thoracic pain, the fever, the pericarditis and an inflammatory syndrom. The corticoth\u00e9rapy is efficient but seems to favour relapses.", "contents": "[Secondary pericarditis after myocardial infarction (author's transl)]. Our study concerns 480 observations about myocardial infarctions. In 10% of the cases, we have found a premature pericarditis diagnosed on the pericardic friction, electric and biologic signes. Some complications such as rythmical troubles, left ventricular dificiency, parietal anevrism are more frequent and increase the prognosis. In 1,2% of the cases, we find a post-infarction syndrom of Dressler, the prognosis of which is mild. The diagnosis is founded on the revival of the thoracic pain, the fever, the pericarditis and an inflammatory syndrom. The corticoth\u00e9rapy is efficient but seems to favour relapses."}
{"id": "PMID:228426", "title": "[Idiopathic cyclic edema in Klinefelter syndrome (author's transl)].", "content": "After a minor abdominal traumatism, M. B., 53 years of age, presents a sudden and acute edematous syndrome. Cardiac, renal, hepatic, nutritional and thyroid etiologies ares rapidly eliminated. A cavography and lymphography reveal the integrity of the drainage pathways. The idiopatic cyclic edematous syndrome is therefore evoked by few clinical details (diurnal weight gain, diurnal oliguria...). Exploration of the renin - angiotensin - aldosterone system, the Landis test and the marked radioactive serum albumin test attest to the exaggeration of capillary permeability. Likewise, it was discovered in this patient, a Klinefelter syndrome which was, until now, unknown. This case poses interesting pathogenic problems since the idiopathic cyclic edematous syndrome is a predominantly feminine disease. Only a few cases were described in the masculine sex and, to our knowledge, this syndrome has never been associated with Klinefelter syndrome.", "contents": "[Idiopathic cyclic edema in Klinefelter syndrome (author's transl)]. After a minor abdominal traumatism, M. B., 53 years of age, presents a sudden and acute edematous syndrome. Cardiac, renal, hepatic, nutritional and thyroid etiologies ares rapidly eliminated. A cavography and lymphography reveal the integrity of the drainage pathways. The idiopatic cyclic edematous syndrome is therefore evoked by few clinical details (diurnal weight gain, diurnal oliguria...). Exploration of the renin - angiotensin - aldosterone system, the Landis test and the marked radioactive serum albumin test attest to the exaggeration of capillary permeability. Likewise, it was discovered in this patient, a Klinefelter syndrome which was, until now, unknown. This case poses interesting pathogenic problems since the idiopathic cyclic edematous syndrome is a predominantly feminine disease. Only a few cases were described in the masculine sex and, to our knowledge, this syndrome has never been associated with Klinefelter syndrome."}
{"id": "PMID:228431", "title": "Operative approach to pancreatic carcinoma.", "content": "It is apparent that we are dealing with a very lethal disease. It is also apparent that this disease is increasing in frequency. In terms of treatment, it is clear that the survival figures between carcinoma of the pancreas and carcinoma of the common duct, papilla of Vater, or duodenum present great differences. The pancreatic tumors do very poorly by comparison. A comparison of the survival figures following a Whipple resection and following a bypass procedure reveal similar results, except when dealing with a very small pancreatic head lesion or when dealing with a malignancy of the papilla of Vater, lower end of common duct, or duodenum. The latter tumor types do better with a Whipple resection than a bypass. A comparison between total pancreatectomy and a Whipple resection for ductal carcinoma of the pancreatic head reveals better results in terms of length of survival following total pancreatectomy as long as one considers only Stage I or Stage II disease and excludes Stage III disease. A Whipple procedure is advocated for carcinoma of the papilla of Vater, common duct, or duodenum, because survival figures are quite good and many patients escape the need for insulin and pancreatic extract replacement. It is too early to evaluate the survival figures that follow regional pancreatectomy.", "contents": "Operative approach to pancreatic carcinoma. It is apparent that we are dealing with a very lethal disease. It is also apparent that this disease is increasing in frequency. In terms of treatment, it is clear that the survival figures between carcinoma of the pancreas and carcinoma of the common duct, papilla of Vater, or duodenum present great differences. The pancreatic tumors do very poorly by comparison. A comparison of the survival figures following a Whipple resection and following a bypass procedure reveal similar results, except when dealing with a very small pancreatic head lesion or when dealing with a malignancy of the papilla of Vater, lower end of common duct, or duodenum. The latter tumor types do better with a Whipple resection than a bypass. A comparison between total pancreatectomy and a Whipple resection for ductal carcinoma of the pancreatic head reveals better results in terms of length of survival following total pancreatectomy as long as one considers only Stage I or Stage II disease and excludes Stage III disease. A Whipple procedure is advocated for carcinoma of the papilla of Vater, common duct, or duodenum, because survival figures are quite good and many patients escape the need for insulin and pancreatic extract replacement. It is too early to evaluate the survival figures that follow regional pancreatectomy."}
{"id": "PMID:228425", "title": "[A hospital problem: agitation in the elderly (author's transl)].", "content": "Tiapride was prescribed for 10 elderly patients with severe behavioural disorders : agitation, disturbed conduct, and agressiveness at the limits of dementia. The dosage was 300 mg orally per day in three divided doses, and treatment was maintained for 30 days. Excellent results were obtained in 8 cases, and 17 of these patients were able to resume normal activities outside the hospital. There was no effect in the other 2 patients. The product was very well-tolerated and in particular there were no sedative manifestations affecting sleep or altertness.", "contents": "[A hospital problem: agitation in the elderly (author's transl)]. Tiapride was prescribed for 10 elderly patients with severe behavioural disorders : agitation, disturbed conduct, and agressiveness at the limits of dementia. The dosage was 300 mg orally per day in three divided doses, and treatment was maintained for 30 days. Excellent results were obtained in 8 cases, and 17 of these patients were able to resume normal activities outside the hospital. There was no effect in the other 2 patients. The product was very well-tolerated and in particular there were no sedative manifestations affecting sleep or altertness."}
{"id": "PMID:228429", "title": "[Salmonella osteomyelitis (authors transl)].", "content": "A case of osteomyelitis due to Salmonella Dublin is reported by the authors who underline the features which distinguish this affection from typhous osteomyelitis, which is completely different.", "contents": "[Salmonella osteomyelitis (authors transl)]. A case of osteomyelitis due to Salmonella Dublin is reported by the authors who underline the features which distinguish this affection from typhous osteomyelitis, which is completely different."}
{"id": "PMID:228433", "title": "Adenoid cystic carcinoma of the minor salivary glands metastatic to the hand.", "content": "An unusual case of adenoid cystic carcinoma of the minor salivary glands of the nasal cavity metastasizing to the hand is presented. The problem of differentiating this lesion from the sweat gland tumor is described and the assistance of special stains is pointed out.", "contents": "Adenoid cystic carcinoma of the minor salivary glands metastatic to the hand. An unusual case of adenoid cystic carcinoma of the minor salivary glands of the nasal cavity metastasizing to the hand is presented. The problem of differentiating this lesion from the sweat gland tumor is described and the assistance of special stains is pointed out."}
{"id": "PMID:228427", "title": "[Chronic lymphocytic leukemia and cystadenocarcinoma of the kidney. A report of one case (author's transl)].", "content": "The association between chronic lymphocytic leukemia and a solid tumor is well known. When the leukemia appears before the tumor a question may be asked : is the tumor a cancer or a localisation of the leukemia ? When the cancer is diagnosed before the leukemia, an other question may be asked : is it a true leukemia or is it a paraneoplasic leukemoid reaction ?", "contents": "[Chronic lymphocytic leukemia and cystadenocarcinoma of the kidney. A report of one case (author's transl)]. The association between chronic lymphocytic leukemia and a solid tumor is well known. When the leukemia appears before the tumor a question may be asked : is the tumor a cancer or a localisation of the leukemia ? When the cancer is diagnosed before the leukemia, an other question may be asked : is it a true leukemia or is it a paraneoplasic leukemoid reaction ?"}
{"id": "PMID:228428", "title": "[Calcification and hernia of an intervertebral disc in a child (author's transl)].", "content": "Cervicobrachial neuralgia and torticolis in a 7 year old child were found to be due to calcification and hernia of an intervertebral disc. Similar cases reported in the published literature are reviewed.", "contents": "[Calcification and hernia of an intervertebral disc in a child (author's transl)]. Cervicobrachial neuralgia and torticolis in a 7 year old child were found to be due to calcification and hernia of an intervertebral disc. Similar cases reported in the published literature are reviewed."}
{"id": "PMID:228437", "title": "Nephroblastoma and multilocular cyst simulating hydronephrosis. A case report.", "content": "An unusual variant of nephroblastoma occurring in association with a multilocular cyst of the kidney is described in a 4-year-old black child.", "contents": "Nephroblastoma and multilocular cyst simulating hydronephrosis. A case report. An unusual variant of nephroblastoma occurring in association with a multilocular cyst of the kidney is described in a 4-year-old black child."}
{"id": "PMID:228443", "title": "Surgical treatment of adenoid cystic carcinoma of the left main bronchus and trachea by left pneumonectomy, resection of 7.5 cm of trachea, and direct reanastomosis of right lung.", "content": "A 23-year-old woman, who had suffered recurrent acute bronchitis, dyspnoea, and stridor, was found to have a tracheal stenosis and complete left main bronchus obstruction. Biopsy of the tumour showed an adenoid cystic carcinoma. After pneumonectomy the trachea was closed through tumour tissue. Two weeks later a right thoracotomy showed that a tumour had invaded the trachea from the carina up to 6 cm and the right stem bronchus for 1 cm. Under extracorporeal circulation 7.5 cm of the trachea and right bronchus were resected. A direct tracheal anastomosis was easy to perform. Spontaneous respiration with efficient coughing returned after five days. Unfortunately, one month later, high fever caused by a lung abscess developed, which provoked a massive haemoptysis with fatal outcome.", "contents": "Surgical treatment of adenoid cystic carcinoma of the left main bronchus and trachea by left pneumonectomy, resection of 7.5 cm of trachea, and direct reanastomosis of right lung. A 23-year-old woman, who had suffered recurrent acute bronchitis, dyspnoea, and stridor, was found to have a tracheal stenosis and complete left main bronchus obstruction. Biopsy of the tumour showed an adenoid cystic carcinoma. After pneumonectomy the trachea was closed through tumour tissue. Two weeks later a right thoracotomy showed that a tumour had invaded the trachea from the carina up to 6 cm and the right stem bronchus for 1 cm. Under extracorporeal circulation 7.5 cm of the trachea and right bronchus were resected. A direct tracheal anastomosis was easy to perform. Spontaneous respiration with efficient coughing returned after five days. Unfortunately, one month later, high fever caused by a lung abscess developed, which provoked a massive haemoptysis with fatal outcome."}
{"id": "PMID:228447", "title": "[Effect of chronic Phenoclor DP6 ingestion of some liver enzymatic activities in rats (author's transl)].", "content": "Rats were fed diet containing 100 ppm (wet weight) of Phenoclor DP6 for 4 weeks. The influence of DP6 was studied by determining the activity of hepatic microsomal enzymes namely : aniline hydroxylase, P-nitroanisole O-demethylase, aminopyrine N-demethylase, methylaniline N-demethylase. The cytochrome P450 and cytochrome b5 liver contents were measured. The activities of Na+ K+ and Mg++ATPases and of G6Phosphatase in the liver were also determined. In the liver of treated rats, the results show a large increased activity of microsomal drug metabolizing enzymes, cytochrome b5 and P450 contents and decreased ATPases and G6Pase specific activities. However total liver activities of ATPases and G6Pase were little modified by ingestion of Phenoclor DP6. The spectra given by cytochrome P450-DP6 binding was a typical type I.", "contents": "[Effect of chronic Phenoclor DP6 ingestion of some liver enzymatic activities in rats (author's transl)]. Rats were fed diet containing 100 ppm (wet weight) of Phenoclor DP6 for 4 weeks. The influence of DP6 was studied by determining the activity of hepatic microsomal enzymes namely : aniline hydroxylase, P-nitroanisole O-demethylase, aminopyrine N-demethylase, methylaniline N-demethylase. The cytochrome P450 and cytochrome b5 liver contents were measured. The activities of Na+ K+ and Mg++ATPases and of G6Phosphatase in the liver were also determined. In the liver of treated rats, the results show a large increased activity of microsomal drug metabolizing enzymes, cytochrome b5 and P450 contents and decreased ATPases and G6Pase specific activities. However total liver activities of ATPases and G6Pase were little modified by ingestion of Phenoclor DP6. The spectra given by cytochrome P450-DP6 binding was a typical type I."}
{"id": "PMID:228451", "title": "Coxsackie B viruses and heart muscle disease in Nigerian adults.", "content": "In 44 Nigerians with heart muscle disease, the percentage of patients who had a fourfold rise or fall to at least one of the Coxsackie B viruses was greater than controls. Patients with heart muscle disease also had significantly higher levels of antibody titres. Antibodies to Coxsackie viruses B2, B3 and B6 were more frequent in their sera than in controls. While these results do not prove a Coxsackie B viral aetiology it is concluded that these viruses could be the cause of cardiac damage and heart failure in some Nigerians. It could also be one of the many adverse factors which produce repeated myocardial damage and thus weaken the heart to the point of failure.", "contents": "Coxsackie B viruses and heart muscle disease in Nigerian adults. In 44 Nigerians with heart muscle disease, the percentage of patients who had a fourfold rise or fall to at least one of the Coxsackie B viruses was greater than controls. Patients with heart muscle disease also had significantly higher levels of antibody titres. Antibodies to Coxsackie viruses B2, B3 and B6 were more frequent in their sera than in controls. While these results do not prove a Coxsackie B viral aetiology it is concluded that these viruses could be the cause of cardiac damage and heart failure in some Nigerians. It could also be one of the many adverse factors which produce repeated myocardial damage and thus weaken the heart to the point of failure."}
{"id": "PMID:228452", "title": "[Relationship between Rous sarcoma virus production in golden hamster cells and the cell cycle].", "content": "The axon terminals of neurosecretory cells, containing elementary granules of neurosecretory materials, have been described on the basis of light and electron microscopy. No allochthonous neurosecretory elements were found in the sinus gland. The discharge of the granules from some terminals of the sinus gland occur with the changed salinity of the environment. There is a great difference in the structure of the sinus gland when salinity is changed. The structure of the sinus gland and its modification under experimental conditions indicate a possibility of neurohormonal regulation of the hydromineral balance.", "contents": "[Relationship between Rous sarcoma virus production in golden hamster cells and the cell cycle]. The axon terminals of neurosecretory cells, containing elementary granules of neurosecretory materials, have been described on the basis of light and electron microscopy. No allochthonous neurosecretory elements were found in the sinus gland. The discharge of the granules from some terminals of the sinus gland occur with the changed salinity of the environment. There is a great difference in the structure of the sinus gland when salinity is changed. The structure of the sinus gland and its modification under experimental conditions indicate a possibility of neurohormonal regulation of the hydromineral balance."}
{"id": "PMID:228448", "title": "Role of adrenergic nerves in blood-induced cerebral vasospasm.", "content": "Cerebral arteries have an abundant supply of adrenergic nerve fibers which are believed to release vasoactive substances responsible for the induction of cerebral vasospasm. To assess the importance of adrenergic nerves in this phenomenon, high doses (600 microgram/ml) of 6-hydroxydopamine (6-OHDA) were used to produce in vitro chemical sympathectomy in bovine middle cerebral artery. 6-OHDA reduced catecholamine fluorescence to undectable limits. H3-norepinephrine re-uptake was reduced to 1.5% of intact controls. Arterial norepinephrine content was reduced by 92%. Contractile responses to norepinephrine, serotonin, and fresh human whole blood were modestly reduced after denervation. This reduction was probably due to alpha receptor inactivation by 6-OHDA, because after protection of the alpha receptors with phentolamine the vessel response was the same as in untreated controls. Contractions in response to aged human whole blood were not affected by denervation. The results suggest that the endogenous release of catecholamines does not play a major role in the initiation or spread of blood-induced vasospasm in large cerebral arteries.", "contents": "Role of adrenergic nerves in blood-induced cerebral vasospasm. Cerebral arteries have an abundant supply of adrenergic nerve fibers which are believed to release vasoactive substances responsible for the induction of cerebral vasospasm. To assess the importance of adrenergic nerves in this phenomenon, high doses (600 microgram/ml) of 6-hydroxydopamine (6-OHDA) were used to produce in vitro chemical sympathectomy in bovine middle cerebral artery. 6-OHDA reduced catecholamine fluorescence to undectable limits. H3-norepinephrine re-uptake was reduced to 1.5% of intact controls. Arterial norepinephrine content was reduced by 92%. Contractile responses to norepinephrine, serotonin, and fresh human whole blood were modestly reduced after denervation. This reduction was probably due to alpha receptor inactivation by 6-OHDA, because after protection of the alpha receptors with phentolamine the vessel response was the same as in untreated controls. Contractions in response to aged human whole blood were not affected by denervation. The results suggest that the endogenous release of catecholamines does not play a major role in the initiation or spread of blood-induced vasospasm in large cerebral arteries."}
{"id": "PMID:228455", "title": "Experiences with the measurement of inhibitory activity of urine and crystallisation inhibitors by different techniques.", "content": "The effect of urine, pyrophosphate (PPi), citrate and diphosphonate on the formation, the growth rate or the aggregation of calcium oxalate or calcium phosphate crystals was measured by 4 different methods. The degree of supersaturation and the area of crystal surface present in the test systems were found to be limiting factors for the action of inhibitors. Citrate and PPi proved to be important urinary inhibitors of the growth of calcium oxalate crystals. Comparison between stone formers and healthy controls revealed a significant lack of PPi in urine of male patients. The inhibitory effect of PPi in urine of healthy people was enhanced by unknown factors. This enhancement could not be found in about 60% of the stone patients. Problems relating to measurement and clinical importance of inhibitors are discussed.", "contents": "Experiences with the measurement of inhibitory activity of urine and crystallisation inhibitors by different techniques. The effect of urine, pyrophosphate (PPi), citrate and diphosphonate on the formation, the growth rate or the aggregation of calcium oxalate or calcium phosphate crystals was measured by 4 different methods. The degree of supersaturation and the area of crystal surface present in the test systems were found to be limiting factors for the action of inhibitors. Citrate and PPi proved to be important urinary inhibitors of the growth of calcium oxalate crystals. Comparison between stone formers and healthy controls revealed a significant lack of PPi in urine of male patients. The inhibitory effect of PPi in urine of healthy people was enhanced by unknown factors. This enhancement could not be found in about 60% of the stone patients. Problems relating to measurement and clinical importance of inhibitors are discussed."}
{"id": "PMID:228456", "title": "[Evaluation of unilateral renal function in urinary obstruction. A comparison of various radioisotope methods (author's transl)].", "content": "The catheter-free determination of the unilateral 131I-hippuran clearance correlates well with the unilateral clearance determination with 99mTc-DMSA in patients without obstruction. In patients with unilateral chronic obstruction the clearance of 131I-hippuran on the average is 13% higher than the clearance determined by the DMSA method. After successful correction of the obstruction the two values are identical. 123I-hippuran is foundin the renal pelvis already after 90 seconds in some cases of marked chronic obstruction. The functioning part of the involved kidney is therefore possibly overestimated whereas the DMSA uptake reflects the actual function. Both radioisotope methods should be applied preoperatively in order to evaluate the individual renal function. Functional scintigraphy in patients with obstruction should preferably be carried out with 123I-hippuran.", "contents": "[Evaluation of unilateral renal function in urinary obstruction. A comparison of various radioisotope methods (author's transl)]. The catheter-free determination of the unilateral 131I-hippuran clearance correlates well with the unilateral clearance determination with 99mTc-DMSA in patients without obstruction. In patients with unilateral chronic obstruction the clearance of 131I-hippuran on the average is 13% higher than the clearance determined by the DMSA method. After successful correction of the obstruction the two values are identical. 123I-hippuran is foundin the renal pelvis already after 90 seconds in some cases of marked chronic obstruction. The functioning part of the involved kidney is therefore possibly overestimated whereas the DMSA uptake reflects the actual function. Both radioisotope methods should be applied preoperatively in order to evaluate the individual renal function. Functional scintigraphy in patients with obstruction should preferably be carried out with 123I-hippuran."}
{"id": "PMID:228464", "title": "Cytology of canine cutaneous round cell tumors. Mast cell tumor, histiocytoma, lymphosarcoma and transmissible venereal tumor.", "content": "Sixty-four canine cutaneous round cell tumors were divided into 25 mast cell tumors, 15 histiocytomas, nine cutaneous lymphosarcomas and 15 transmissible venereal tumors. The final diagnosis was made from cytologic, clinical and histologic findings. Cytologic features were significantly distinctive in mast cell tumor, transmissible venereal tumor, and most cases of histiocytoma and lymphosarcoma to allow a diagnostic opinion. This opinion was supported by subsequent histologic examination. In some instances cytology was considered essential in rendering a diagnostic opinion even though histology was available.", "contents": "Cytology of canine cutaneous round cell tumors. Mast cell tumor, histiocytoma, lymphosarcoma and transmissible venereal tumor. Sixty-four canine cutaneous round cell tumors were divided into 25 mast cell tumors, 15 histiocytomas, nine cutaneous lymphosarcomas and 15 transmissible venereal tumors. The final diagnosis was made from cytologic, clinical and histologic findings. Cytologic features were significantly distinctive in mast cell tumor, transmissible venereal tumor, and most cases of histiocytoma and lymphosarcoma to allow a diagnostic opinion. This opinion was supported by subsequent histologic examination. In some instances cytology was considered essential in rendering a diagnostic opinion even though histology was available."}
{"id": "PMID:228473", "title": "[Purification of coronaviruses from contaminated cattle feces].", "content": "A scheme was worked out for the obtaining of purified Corona viruses from fecal extracts, which include: centrifugation in an discontinued gradient of sucrose 20--45 per cent, gel filtration through a Sephadex 4B column, and centrifugation in a linear gradient of sucrose 10--50 per cent. By means of such purification the virions remain morphologically intact in sucrose density of 1.11--1.14 gr/cm3, containing no ballast proteins. As many as five polypeptides are demonstrated in polyacrylamide electrophoresis.", "contents": "[Purification of coronaviruses from contaminated cattle feces]. A scheme was worked out for the obtaining of purified Corona viruses from fecal extracts, which include: centrifugation in an discontinued gradient of sucrose 20--45 per cent, gel filtration through a Sephadex 4B column, and centrifugation in a linear gradient of sucrose 10--50 per cent. By means of such purification the virions remain morphologically intact in sucrose density of 1.11--1.14 gr/cm3, containing no ballast proteins. As many as five polypeptides are demonstrated in polyacrylamide electrophoresis."}
{"id": "PMID:228489", "title": "[Participation of phosphopeptides in oxidative amino acid exchange in brain tissue].", "content": "Specific proteins and phosphopeptides of nervous tissue soluble in acidified organic solvents have been shown to have an active participation in the metabolism of ammonia. Nitrogen phosphopeptides (amides) bound to phosphate residues which are non stable in acids. It was shown that acid-labil nitrogen (amide group) of phosphopeptides, bound to phosphate risidue, participates in the metabolism of ammonia formed during the oxidative deamination of amino acids. The data obtained indicate that 3'--5'-AMP dependent proteinkinase participates in the phosphorilation of phosphopeptides.", "contents": "[Participation of phosphopeptides in oxidative amino acid exchange in brain tissue]. Specific proteins and phosphopeptides of nervous tissue soluble in acidified organic solvents have been shown to have an active participation in the metabolism of ammonia. Nitrogen phosphopeptides (amides) bound to phosphate residues which are non stable in acids. It was shown that acid-labil nitrogen (amide group) of phosphopeptides, bound to phosphate risidue, participates in the metabolism of ammonia formed during the oxidative deamination of amino acids. The data obtained indicate that 3'--5'-AMP dependent proteinkinase participates in the phosphorilation of phosphopeptides."}
{"id": "PMID:228491", "title": "[Possible role of neuropeptides in regulating nucleic acid biosynthesis in the brain].", "content": "It has been studied the role of intracysternal administration of neuropeptides--five analogous of 8-lysinvasopressin (LVP) [Des-9-Gly-cine-amide-LVP (DGLVP), Tri-Gly-LVP, deamino-LVP (1--beta-mercaptopropionic acid-LVP), Leu4-LVP, Asn1,6-LVP] and two cardiotrop hexapeptides (acetylated and non) separated from the hypothalamus in the regulation of various types of RNA (GC and AU types n-RNA, r-RNA, t-RNA) biosynthesis in the brain. Using the combined method of phenol extraction, differential ultracentrifugation, gel-filtration and ultraviolet spectroscory of various types of RNA has been shown the increase in the content of r-RNA and t-RNA under the influence of DGLVP, Leu4-LVP and cardiotrop hexapeptide. Deamino-LVP, Tri-Gly-LVP and acetylated hexapeptide stimulate the rise in the content of r-RNA and AU type n-RNA (precursor of m-RNA). Ans1,6-LVP shows a nonspecific influence on the biosynthesis of the brain RNA. It has been suggested a hypothesis about a participation of the neuropeptides in the regulation of various types of the brain RNA biosynthesis, as a primary messanger (starting signals) during the stimulation of the initiation of cycloadenylate- and cycloguanylate-sensitive transcription, via phosphorylation of diverse RNA-polymerases. It was given a scheme of interaction between the messanger conception of neuropeptides and cyclic-3', 5'-monophosphate nucleotide-dependent transcription by which the cycloadenylate-dependent transcription appears to play a great role in the r-RNA and t-RNA biosynthesis and the cycloguanylate-dependent transcription -- in the biosynthesis of m-RNA.", "contents": "[Possible role of neuropeptides in regulating nucleic acid biosynthesis in the brain]. It has been studied the role of intracysternal administration of neuropeptides--five analogous of 8-lysinvasopressin (LVP) [Des-9-Gly-cine-amide-LVP (DGLVP), Tri-Gly-LVP, deamino-LVP (1--beta-mercaptopropionic acid-LVP), Leu4-LVP, Asn1,6-LVP] and two cardiotrop hexapeptides (acetylated and non) separated from the hypothalamus in the regulation of various types of RNA (GC and AU types n-RNA, r-RNA, t-RNA) biosynthesis in the brain. Using the combined method of phenol extraction, differential ultracentrifugation, gel-filtration and ultraviolet spectroscory of various types of RNA has been shown the increase in the content of r-RNA and t-RNA under the influence of DGLVP, Leu4-LVP and cardiotrop hexapeptide. Deamino-LVP, Tri-Gly-LVP and acetylated hexapeptide stimulate the rise in the content of r-RNA and AU type n-RNA (precursor of m-RNA). Ans1,6-LVP shows a nonspecific influence on the biosynthesis of the brain RNA. It has been suggested a hypothesis about a participation of the neuropeptides in the regulation of various types of the brain RNA biosynthesis, as a primary messanger (starting signals) during the stimulation of the initiation of cycloadenylate- and cycloguanylate-sensitive transcription, via phosphorylation of diverse RNA-polymerases. It was given a scheme of interaction between the messanger conception of neuropeptides and cyclic-3', 5'-monophosphate nucleotide-dependent transcription by which the cycloadenylate-dependent transcription appears to play a great role in the r-RNA and t-RNA biosynthesis and the cycloguanylate-dependent transcription -- in the biosynthesis of m-RNA."}
{"id": "PMID:228492", "title": "[Copper-containing brain proteins].", "content": "Three copper-containing proteins were obtained from bovine brain soluble fraction. Two of them were purified to electrophoretically homogenous states. Some physicochemical properties of these proteins were studied. From mitochondrial fraction of grey matter of bovine brain cytochrome oxidase was obtained, which was similar to that obtained from cardiac muscle.", "contents": "[Copper-containing brain proteins]. Three copper-containing proteins were obtained from bovine brain soluble fraction. Two of them were purified to electrophoretically homogenous states. Some physicochemical properties of these proteins were studied. From mitochondrial fraction of grey matter of bovine brain cytochrome oxidase was obtained, which was similar to that obtained from cardiac muscle."}
{"id": "PMID:228493", "title": "[Chemistry and biology of hypothalamic cardioactive proteins and peptides].", "content": "The data presented concern the chemistry and biology of cardiotrop peptides and proteins isolated by us from the hypothalamus. The molecular mechanisms of the effect of neurohormone \"C\" (NC) as well as of a new cardiotrop hexapeptide from cattle hypothalamus are discussed. In in vitro studies on homogenates NC has been found to inhibit greatly not only 3'--5'-cyclo-AMP phosphodiesterase activity of brain and heart but also 3'--5'-cyclo-GMP phosphodiesterase activity. NC has been shown to be bound to specific proteins and to the regulatory unit of cyclo-AMP-dependent histone kinase of brain. It seems to compete with cyclo-AMP for the same proteins and is considered to be a regulator of intracellular cyclic nucleotides. NC has been shown to be combined to specific proteins in brain with non covalent bonds. A new cardiotrop hexapeptide has been shown to be present in bovine hypothalamus and its chemical structure has been found to be Tyr-Leu-Gly-Arg-Pro-Gly-amide. The acetylated form of this hexapeptide, which may be also present in brain, is much more active. The radioimmunochemical experiments carried out with antiserum 744 (from prof. Schally) by us have confirmed the existence of this hexapeptide and other fragments of LH-RH in the bovine hypothalamus. The effect of this hexapeptide on cardiac function and metabolism has been compared with a number of polypeptides (luliberin fragments). The hexapeptide has been shown to have not only cardiotropic but also a hypoglycaemic effect. It enhances the secretion of insulin and counteracts the inhibitory action of somatostatin on the insular apparatus. The hexapeptide produces significant changes in the activities of phosphorylase a and b as well as in that of phosphoprotein phosphatases. It reduces the amount of kinines in blood. Certain fractions of substance P, have been shown to have cardiotrop actitivty--they increase the rate of blood leaving the heart. The organotrop effects of a number of peptide neurohormones are discussed in connection with the hexapeptide. The results obtained have shown that the mechanisms underlying the effects of the cardioactive substances found by us are quite different. The data presented show that in brain a number of chemical factors (mainly peptides) are formed, which are involved in the regulation of heart function.", "contents": "[Chemistry and biology of hypothalamic cardioactive proteins and peptides]. The data presented concern the chemistry and biology of cardiotrop peptides and proteins isolated by us from the hypothalamus. The molecular mechanisms of the effect of neurohormone \"C\" (NC) as well as of a new cardiotrop hexapeptide from cattle hypothalamus are discussed. In in vitro studies on homogenates NC has been found to inhibit greatly not only 3'--5'-cyclo-AMP phosphodiesterase activity of brain and heart but also 3'--5'-cyclo-GMP phosphodiesterase activity. NC has been shown to be bound to specific proteins and to the regulatory unit of cyclo-AMP-dependent histone kinase of brain. It seems to compete with cyclo-AMP for the same proteins and is considered to be a regulator of intracellular cyclic nucleotides. NC has been shown to be combined to specific proteins in brain with non covalent bonds. A new cardiotrop hexapeptide has been shown to be present in bovine hypothalamus and its chemical structure has been found to be Tyr-Leu-Gly-Arg-Pro-Gly-amide. The acetylated form of this hexapeptide, which may be also present in brain, is much more active. The radioimmunochemical experiments carried out with antiserum 744 (from prof. Schally) by us have confirmed the existence of this hexapeptide and other fragments of LH-RH in the bovine hypothalamus. The effect of this hexapeptide on cardiac function and metabolism has been compared with a number of polypeptides (luliberin fragments). The hexapeptide has been shown to have not only cardiotropic but also a hypoglycaemic effect. It enhances the secretion of insulin and counteracts the inhibitory action of somatostatin on the insular apparatus. The hexapeptide produces significant changes in the activities of phosphorylase a and b as well as in that of phosphoprotein phosphatases. It reduces the amount of kinines in blood. Certain fractions of substance P, have been shown to have cardiotrop actitivty--they increase the rate of blood leaving the heart. The organotrop effects of a number of peptide neurohormones are discussed in connection with the hexapeptide. The results obtained have shown that the mechanisms underlying the effects of the cardioactive substances found by us are quite different. The data presented show that in brain a number of chemical factors (mainly peptides) are formed, which are involved in the regulation of heart function."}
{"id": "PMID:228495", "title": "[Properties and isoenzyme contents of glucose-6-phosphatase of normal and tumor cell microsomes].", "content": "Studies on the properties and isoenzymic content of glucose-6-phosphatase (E. C. 3.1.3.9.) of normal and tumor cells microsomes allowed the following conclusion to be made: the localization of the enzyme in the membranes of endoplasmatic reticulum of both types of cells is identical. The tumor microsomes are characterized (irrespective of the blastomogenic factor inducing them) by a decreased activity of the enzyme at pH 6.75, a relatively increased activity of the latter at pH 7.5. Solubilization of the enzyme was performed by a new technic i. e. the acetone treatment of microsomes. Rechromatography of most active fractions on Sephadex G-200 has revealed less number of the enzyme isoforms of tumor cell microsomes.", "contents": "[Properties and isoenzyme contents of glucose-6-phosphatase of normal and tumor cell microsomes]. Studies on the properties and isoenzymic content of glucose-6-phosphatase (E. C. 3.1.3.9.) of normal and tumor cells microsomes allowed the following conclusion to be made: the localization of the enzyme in the membranes of endoplasmatic reticulum of both types of cells is identical. The tumor microsomes are characterized (irrespective of the blastomogenic factor inducing them) by a decreased activity of the enzyme at pH 6.75, a relatively increased activity of the latter at pH 7.5. Solubilization of the enzyme was performed by a new technic i. e. the acetone treatment of microsomes. Rechromatography of most active fractions on Sephadex G-200 has revealed less number of the enzyme isoforms of tumor cell microsomes."}
{"id": "PMID:228498", "title": "[Concentration of the poliomyelitis virus from water on FP-brand material].", "content": "A method of filtration through FP cloth (Petryanov's cloth) has been suggested for concentration of small virus quantities from large volumes of water. The effectiveness of virus removal from water of different degrees of contamination at virus concentrations of 0.05--0.1--0.5--2.5--12.5 PFU/ml was studied. About 88--100% of the initial virus content was removed from sewage, 80--90% from river water, 10--90% from tap water. When the effect of the eluting solutions for the removal of the virus retained on the filter was compared, 1 M NaCl solution in glycocol buffer, pH 11.5, was found to be the most effective. The procedure is characterized by a high rate of filtration, low labour consumption, and simple equipment for filtration.", "contents": "[Concentration of the poliomyelitis virus from water on FP-brand material]. A method of filtration through FP cloth (Petryanov's cloth) has been suggested for concentration of small virus quantities from large volumes of water. The effectiveness of virus removal from water of different degrees of contamination at virus concentrations of 0.05--0.1--0.5--2.5--12.5 PFU/ml was studied. About 88--100% of the initial virus content was removed from sewage, 80--90% from river water, 10--90% from tap water. When the effect of the eluting solutions for the removal of the virus retained on the filter was compared, 1 M NaCl solution in glycocol buffer, pH 11.5, was found to be the most effective. The procedure is characterized by a high rate of filtration, low labour consumption, and simple equipment for filtration."}
{"id": "PMID:228496", "title": "[Initial stages of the interaction of murine interferon with L929 cells].", "content": "After contact with mouse culture interferon in the cold, the resistance to viruses in L cells develops only after the cells are placed into a thermostate at 37 degrees C. The use of colcemide destroying microtubules prevents the development of this resistance at an early (actinomycin-sensitive) stage of interferon-cell interaction. In the actinomycin-resistant stage, however, colcemide practically exerts no influence on the interferon-induced resistance to viruses.", "contents": "[Initial stages of the interaction of murine interferon with L929 cells]. After contact with mouse culture interferon in the cold, the resistance to viruses in L cells develops only after the cells are placed into a thermostate at 37 degrees C. The use of colcemide destroying microtubules prevents the development of this resistance at an early (actinomycin-sensitive) stage of interferon-cell interaction. In the actinomycin-resistant stage, however, colcemide practically exerts no influence on the interferon-induced resistance to viruses."}
{"id": "PMID:228497", "title": "[Interferon-producing activity of bone marrow cells treated with mRNA for interferon when transplanted to irradiated mice].", "content": "Inoculation into irradiated (800--850 r) mice of syngeneic bone marrow cells treated with mRNA for interferon (mRNA-If) obtained from chick cells induced with UV-irradiated Newcastle disease virus was accompanied by the appearance in the blood of the animals of a substance with the properties of interferon, inhibiting the cytopathic effect of vesicular stomatitis virus in chick embryo cells but not in mouse L cells. Chicken interferon was detected in the blood of the experimental animals for 7--10 days after transplantation of mRNA-If-treated cells.", "contents": "[Interferon-producing activity of bone marrow cells treated with mRNA for interferon when transplanted to irradiated mice]. Inoculation into irradiated (800--850 r) mice of syngeneic bone marrow cells treated with mRNA for interferon (mRNA-If) obtained from chick cells induced with UV-irradiated Newcastle disease virus was accompanied by the appearance in the blood of the animals of a substance with the properties of interferon, inhibiting the cytopathic effect of vesicular stomatitis virus in chick embryo cells but not in mouse L cells. Chicken interferon was detected in the blood of the experimental animals for 7--10 days after transplantation of mRNA-If-treated cells."}
{"id": "PMID:228512", "title": "[Benign multilocular cystic nephroma versus cystic nephroblastoma. A review and classification of cystic metanephric neoplasms (author's transl)].", "content": "A review of reported cases of cystic metanephric tumors is given. It is shown that among these neoplasms two distinct pathologic entities exist: the cystic nephroblastoma and the benign multilocular cystic nephroma. The former, a benign variant of Wilms' tumor, is found in children of younger age. Its possible precursor is the infantile form of nephroblastomatosis. The second neoplasm, a clinically and biologically benign tumor, occurs in older children and in half of the cases it is also encountered in adults. It derives from metanephric hamartomas which have their origin in the huvenile form of nephroblastomatosis.", "contents": "[Benign multilocular cystic nephroma versus cystic nephroblastoma. A review and classification of cystic metanephric neoplasms (author's transl)]. A review of reported cases of cystic metanephric tumors is given. It is shown that among these neoplasms two distinct pathologic entities exist: the cystic nephroblastoma and the benign multilocular cystic nephroma. The former, a benign variant of Wilms' tumor, is found in children of younger age. Its possible precursor is the infantile form of nephroblastomatosis. The second neoplasm, a clinically and biologically benign tumor, occurs in older children and in half of the cases it is also encountered in adults. It derives from metanephric hamartomas which have their origin in the huvenile form of nephroblastomatosis."}
{"id": "PMID:228513", "title": "[Passive protection tests in the mouse with pertussis immunoglobulin (author's transl)].", "content": "A reproducible method for potency-testing of pertussis-sera and - immunoglobulines in a neutralisation test in the mouse is described. The tests were done on two human immunoglobulines, one crude immune serum from the rabbit, and two purified resp. concentrated rabbit immune sera, one of which - the US-Standard for Pertussis Sera - was used as the standard preparation for the potency evaluation. There is no correlation between the results of the neutralisation test and the agglutination titer among the different preparations. That means, the agglutination titer is not suitable for comparing the potency of pertussis sera resp. - immunoglobulines. It seems necessary to establish a uniforme method as well as a standard preparation for potency testing of pertussis sera and - immunoglobulines on the basis of the neutralisation test in the mouse - at least on the European level.", "contents": "[Passive protection tests in the mouse with pertussis immunoglobulin (author's transl)]. A reproducible method for potency-testing of pertussis-sera and - immunoglobulines in a neutralisation test in the mouse is described. The tests were done on two human immunoglobulines, one crude immune serum from the rabbit, and two purified resp. concentrated rabbit immune sera, one of which - the US-Standard for Pertussis Sera - was used as the standard preparation for the potency evaluation. There is no correlation between the results of the neutralisation test and the agglutination titer among the different preparations. That means, the agglutination titer is not suitable for comparing the potency of pertussis sera resp. - immunoglobulines. It seems necessary to establish a uniforme method as well as a standard preparation for potency testing of pertussis sera and - immunoglobulines on the basis of the neutralisation test in the mouse - at least on the European level."}
{"id": "PMID:228514", "title": "[Microbial emission, immission and changes in the germ count in the cooling water during operation of wet cooling towers ii. communication: measuring methods, emission values and changes in the germ count in the cooling system (author's transl)].", "content": "The second in the series \"Microbial emission, immission and changes in the germ count in the cooling water of wet cooling towers\" describes measuring methods and results of the measurements for determining the emission values and the changes in the germ count in the cooling system. The content of colony-forming units (KBE) in the cooling water varied widely, depending on the germ content of the surface water and the preparation of the cooling water (filtration, chemical conditioning). In summer the KBE values were as a rule higher than the values recorded in winter (factor of about 10). The introduction of cooling tower water into the surface water thus did not result in any noticeable changes in germ content, either in summer or in winter. An emission rate of 8.3 10(7) KBE/s (CSA) measured at the top of the cooling tower was the maximum emission value recorded. This resulted in a total germ content in the plume of 1.2 . 10(4) KBE/m3. In order to place this finding into perspective, it should be noted that fluctuations in the KBE values of the air of considerably more than 1000 KBE/m3 can occur because of biological release and meteorological conditions alone (see IVth communication). The KBE-P values recorded (content of particles with units which are capable of forming colonies) in the plume were of the same order as the KBE values. From this it can be concluded that the drops of cooling water which are swept away with the plume are normally only charged with individual colony-forming units. It is worth noting that the KBE values of the plume are only indirectly dependent on the KBE values of the cooling water used in the cooling tower.", "contents": "[Microbial emission, immission and changes in the germ count in the cooling water during operation of wet cooling towers ii. communication: measuring methods, emission values and changes in the germ count in the cooling system (author's transl)]. The second in the series \"Microbial emission, immission and changes in the germ count in the cooling water of wet cooling towers\" describes measuring methods and results of the measurements for determining the emission values and the changes in the germ count in the cooling system. The content of colony-forming units (KBE) in the cooling water varied widely, depending on the germ content of the surface water and the preparation of the cooling water (filtration, chemical conditioning). In summer the KBE values were as a rule higher than the values recorded in winter (factor of about 10). The introduction of cooling tower water into the surface water thus did not result in any noticeable changes in germ content, either in summer or in winter. An emission rate of 8.3 10(7) KBE/s (CSA) measured at the top of the cooling tower was the maximum emission value recorded. This resulted in a total germ content in the plume of 1.2 . 10(4) KBE/m3. In order to place this finding into perspective, it should be noted that fluctuations in the KBE values of the air of considerably more than 1000 KBE/m3 can occur because of biological release and meteorological conditions alone (see IVth communication). The KBE-P values recorded (content of particles with units which are capable of forming colonies) in the plume were of the same order as the KBE values. From this it can be concluded that the drops of cooling water which are swept away with the plume are normally only charged with individual colony-forming units. It is worth noting that the KBE values of the plume are only indirectly dependent on the KBE values of the cooling water used in the cooling tower."}
{"id": "PMID:228516", "title": "[Development of a cellular immune response in a highly cancer-susceptible C3H/He strain of mice and its nonfactor substrain C3H/f after the transplantation of a syngeneic mammary gland tumor].", "content": "Syngeneic mammary gland tumor (MMT-1) grew slower in non-factor C3H/f (MTV-L) mice than in wirus-positive C3H/He (MTV-S) mice. The immunization of mice with tumor (MMT-1), inoculated and later excised, revealed a higher immune reactivity in the mice of the non-factor substrain. In studying the dynamics of the cytotoxic activity of lymphocytes in regional lymph nodes cytotoxically active lymphocytes were found to appear in C3H/f mice on day 6 after the inoculation of tumor (MMT-1), while the areactive state of lymphocytes was observed in C3H/He mice on days 3 and 24 and in C3H/f mice on day 24 after the inoculation of tumor (MMT-1). Spleen lymphocytes in C3H/f mice had no cytotoxic effect on tumor cells.", "contents": "[Development of a cellular immune response in a highly cancer-susceptible C3H/He strain of mice and its nonfactor substrain C3H/f after the transplantation of a syngeneic mammary gland tumor]. Syngeneic mammary gland tumor (MMT-1) grew slower in non-factor C3H/f (MTV-L) mice than in wirus-positive C3H/He (MTV-S) mice. The immunization of mice with tumor (MMT-1), inoculated and later excised, revealed a higher immune reactivity in the mice of the non-factor substrain. In studying the dynamics of the cytotoxic activity of lymphocytes in regional lymph nodes cytotoxically active lymphocytes were found to appear in C3H/f mice on day 6 after the inoculation of tumor (MMT-1), while the areactive state of lymphocytes was observed in C3H/He mice on days 3 and 24 and in C3H/f mice on day 24 after the inoculation of tumor (MMT-1). Spleen lymphocytes in C3H/f mice had no cytotoxic effect on tumor cells."}
{"id": "PMID:228520", "title": "The distribution of degenerative changes in INH neuropathy. Further evidence for focal axonal lesions.", "content": "Rats were given isoniazid either in a single large dose or continuously in drinking water and killed 5--105 days later. The distribution of degenerating fibres in various nerves (sensory and mixed) and in various sites along nerves and spinal roots was studied by light and electron microscopy. It was found that sensory nerves tended to be less affected than motor, and degeneration was more proximal in the latter. It was concluded that the pattern of degeneration and regeneration supported the view that the initial metabolic lesion is in the axon, rather than in the cell body.", "contents": "The distribution of degenerative changes in INH neuropathy. Further evidence for focal axonal lesions. Rats were given isoniazid either in a single large dose or continuously in drinking water and killed 5--105 days later. The distribution of degenerating fibres in various nerves (sensory and mixed) and in various sites along nerves and spinal roots was studied by light and electron microscopy. It was found that sensory nerves tended to be less affected than motor, and degeneration was more proximal in the latter. It was concluded that the pattern of degeneration and regeneration supported the view that the initial metabolic lesion is in the axon, rather than in the cell body."}
{"id": "PMID:228521", "title": "Neuronal degeneration in the brain of the brindled mouse. I. Chromological studies on the long-surviving group.", "content": "Brindled mutant mouse (MObr) is clinically closely similar to kinky hair syndrome (KHS) in humans. Hemizygous males (MObr/Y) of this mutant usually cannot survive beyond the 15th -- 16th postnatal day. However, some were found to survive into the adult life. Extensive neuronal degeneration in the cerebral cortex was a prominent neuropathological feature of MObr/Y (Yajima and Suzuki, 1979a). In the long surviving one, however, such neuronal degeneration gradually disappeared and cortical neuronal loss and axonal degeneration of the underlying white matter were the predominant neuropathological features. which are closely similar to those of KHS, in particular in those patients who survive for more than 1 year. On the basis of our observations on the brain of MObr/Y mice, we hypothesized the possible chronological events on the development of neuropathological lesions in KHS in humans.", "contents": "Neuronal degeneration in the brain of the brindled mouse. I. Chromological studies on the long-surviving group. Brindled mutant mouse (MObr) is clinically closely similar to kinky hair syndrome (KHS) in humans. Hemizygous males (MObr/Y) of this mutant usually cannot survive beyond the 15th -- 16th postnatal day. However, some were found to survive into the adult life. Extensive neuronal degeneration in the cerebral cortex was a prominent neuropathological feature of MObr/Y (Yajima and Suzuki, 1979a). In the long surviving one, however, such neuronal degeneration gradually disappeared and cortical neuronal loss and axonal degeneration of the underlying white matter were the predominant neuropathological features. which are closely similar to those of KHS, in particular in those patients who survive for more than 1 year. On the basis of our observations on the brain of MObr/Y mice, we hypothesized the possible chronological events on the development of neuropathological lesions in KHS in humans."}
{"id": "PMID:228522", "title": "Neuronal degeneration in the brain of the brindled mouse. II. Ultrastructure of neuronal inclusions in the cerebral cortex.", "content": "Two types of intra-cytoplasmic inclusions were observed in many cortical neurons of hemizygous brindled mutant mice (MObr/Y) which survived for more than 1 month. One type is an electron-lucent vacuole containing numerous vesicles and membrane fragments, some arranged concentrically, and the other consisted of electron-dense matrix with myelin figures. These inclusions were, as a rule, found near the axonal hillock where abnormally enlarged mitochondria were often present. In view of the presence of many features suggestive of autophagic vacuoles and absence of such inclusions in the oldest mice (91 days old), we hypothesize that these inclusions probably represent a focal repairing process of neurons from the sublethal injury.", "contents": "Neuronal degeneration in the brain of the brindled mouse. II. Ultrastructure of neuronal inclusions in the cerebral cortex. Two types of intra-cytoplasmic inclusions were observed in many cortical neurons of hemizygous brindled mutant mice (MObr/Y) which survived for more than 1 month. One type is an electron-lucent vacuole containing numerous vesicles and membrane fragments, some arranged concentrically, and the other consisted of electron-dense matrix with myelin figures. These inclusions were, as a rule, found near the axonal hillock where abnormally enlarged mitochondria were often present. In view of the presence of many features suggestive of autophagic vacuoles and absence of such inclusions in the oldest mice (91 days old), we hypothesize that these inclusions probably represent a focal repairing process of neurons from the sublethal injury."}
{"id": "PMID:228523", "title": "Morphological observations in the nervous system of prenatal mucopolysaccharidosis II (M. Hunter).", "content": "Light and electron microscopic finding in the nervous system of a 23-week-old fetus are reported, in which MPS II was diagnosed prenatally. The degrees of myelination and neuronal differentiation were similar as in a normal fetus of the same age. A storage of mucopolysaccharides in typical vacuolar inclusion bodies was present throughout the peripheral and central nervous system, mainly in cells of mesenchymal origin. \"Zebra\" bodies and granulo-membranous bodies, which are thought to represent secondard ganglioside accumulation were only found in the well developed neurons of the spinal cord and spinal ganglia, but not in the poorly developed neurons of the cerebellar and cerebral cortex. Mucopolysaccharide storage in endothelial cells of cerebral bood vessels precedes the appearance of lipid storgae in cerebral neurons.", "contents": "Morphological observations in the nervous system of prenatal mucopolysaccharidosis II (M. Hunter). Light and electron microscopic finding in the nervous system of a 23-week-old fetus are reported, in which MPS II was diagnosed prenatally. The degrees of myelination and neuronal differentiation were similar as in a normal fetus of the same age. A storage of mucopolysaccharides in typical vacuolar inclusion bodies was present throughout the peripheral and central nervous system, mainly in cells of mesenchymal origin. \"Zebra\" bodies and granulo-membranous bodies, which are thought to represent secondard ganglioside accumulation were only found in the well developed neurons of the spinal cord and spinal ganglia, but not in the poorly developed neurons of the cerebellar and cerebral cortex. Mucopolysaccharide storage in endothelial cells of cerebral bood vessels precedes the appearance of lipid storgae in cerebral neurons."}
{"id": "PMID:228528", "title": "Adrenergic and novel non-adrenergic neuronal mechanisms in the control of smooth muscle activity in the human oviduct.", "content": "The isthmic portion of human Fallopian tubes was excised during surgery and the ampullary-isthmic junction was identified. The external, longitudinal and the inner, circular muscle layers of this structure were then mechanically separated. The contractile activity of thin strips from these layers was studied isometrically in organ bath experiments. Administration of various adrenoceptor agonists and antagonists revealed that the responses of the longitudinal smooth muscle are primarily mediated by alpha-adrenoceptors while there is a marked dominance of beta-adrenoceptor-mediated effects in the circular layer. Transmural nerve stimulation to those caused by exogenous noradrenaline, although nerve-mediated inhibition of circular muscle activity was not abolished entirely by propranolol, atropine or guanethidine, but by tetradotoxine, indicating the existence of a hitherto unknown non-adrenergic, non-cholinergic, inhibitory neurogenic mechanism. The results support the concept of a specific sphincter-like function controlling ovum transport at the human oviductal isthmus, and that this sphincter may be controlled by both adrenergic nerves and nerves liberating an unidentified transmitter substance.", "contents": "Adrenergic and novel non-adrenergic neuronal mechanisms in the control of smooth muscle activity in the human oviduct. The isthmic portion of human Fallopian tubes was excised during surgery and the ampullary-isthmic junction was identified. The external, longitudinal and the inner, circular muscle layers of this structure were then mechanically separated. The contractile activity of thin strips from these layers was studied isometrically in organ bath experiments. Administration of various adrenoceptor agonists and antagonists revealed that the responses of the longitudinal smooth muscle are primarily mediated by alpha-adrenoceptors while there is a marked dominance of beta-adrenoceptor-mediated effects in the circular layer. Transmural nerve stimulation to those caused by exogenous noradrenaline, although nerve-mediated inhibition of circular muscle activity was not abolished entirely by propranolol, atropine or guanethidine, but by tetradotoxine, indicating the existence of a hitherto unknown non-adrenergic, non-cholinergic, inhibitory neurogenic mechanism. The results support the concept of a specific sphincter-like function controlling ovum transport at the human oviductal isthmus, and that this sphincter may be controlled by both adrenergic nerves and nerves liberating an unidentified transmitter substance."}
{"id": "PMID:228529", "title": "Release of 3H-nucleosides from 3H-adenine labelled hypothalamic synaptosomes.", "content": "[3H]adenine was taken up by a crude hypothalamic synaptosomal fraction and incorporated into mainly nucleotides. The synaptosomes were superfused and after the initial washout a steady fractional release rate of 0.5-1% of the content/min was found. Electrical pulses (2 ms, 50 Hz, 10-20 mA, 4 min) and veratridine (10 microM, 4 min) induced a Ca++-dependent increase in purine release rate. K+ (30 mM, 4 min) caused a largely Ca++-independent increase. Most of the released material co-chromatographed with adenosine, inosine and hypoxanthine, while little or no nucleotide material was detected. Release of endogenous adenosine, inosine and hypoxanthine was detected by high performance liquid chromatography. However, following hypo-osmotic shock most of the released material was in nucleotides. The removal of glucose from the medium increased the fractional release rate 2-3 fold. Histamine, acetylcholine and glutamate were without effect. High amounts of noradrenaline caused an EGTA-inhibited release of purines, which was un-affected by propranolol or phentolamine. It is suggested that purines are released from neuronal structures and that the release reflects increased energy consumption and/or decreased energy production.", "contents": "Release of 3H-nucleosides from 3H-adenine labelled hypothalamic synaptosomes. [3H]adenine was taken up by a crude hypothalamic synaptosomal fraction and incorporated into mainly nucleotides. The synaptosomes were superfused and after the initial washout a steady fractional release rate of 0.5-1% of the content/min was found. Electrical pulses (2 ms, 50 Hz, 10-20 mA, 4 min) and veratridine (10 microM, 4 min) induced a Ca++-dependent increase in purine release rate. K+ (30 mM, 4 min) caused a largely Ca++-independent increase. Most of the released material co-chromatographed with adenosine, inosine and hypoxanthine, while little or no nucleotide material was detected. Release of endogenous adenosine, inosine and hypoxanthine was detected by high performance liquid chromatography. However, following hypo-osmotic shock most of the released material was in nucleotides. The removal of glucose from the medium increased the fractional release rate 2-3 fold. Histamine, acetylcholine and glutamate were without effect. High amounts of noradrenaline caused an EGTA-inhibited release of purines, which was un-affected by propranolol or phentolamine. It is suggested that purines are released from neuronal structures and that the release reflects increased energy consumption and/or decreased energy production."}
{"id": "PMID:228526", "title": "Central effects of octopamine administered into the lateral ventricle of rats.", "content": "Central effects of octopamine administered into the lateral ventricle of rats. Acta physiol. pol., 1979, 30 (4): 445--453. Octopamine (100, 250 and 500 micrograms/rat i.v.c.) exerted a stimulating effect on the central nervous system in rats, which was evidenced by increased spontaneous and basal motor activity, increased exploratory activity in the free-field test, and also increased motor activity in reserpinised rats pretreated with alpha-MT or nialamide. Octopamine decreased the body temperature and prolonged the duration of hexobarbital-induced sleep, and increased amphetamine-induced hyperactivity. Locomotor agitation after octopamine injection was inhibited by phenoxybenzamine and yohimbine in a dose of 10 mg/kg i.p.", "contents": "Central effects of octopamine administered into the lateral ventricle of rats. Central effects of octopamine administered into the lateral ventricle of rats. Acta physiol. pol., 1979, 30 (4): 445--453. Octopamine (100, 250 and 500 micrograms/rat i.v.c.) exerted a stimulating effect on the central nervous system in rats, which was evidenced by increased spontaneous and basal motor activity, increased exploratory activity in the free-field test, and also increased motor activity in reserpinised rats pretreated with alpha-MT or nialamide. Octopamine decreased the body temperature and prolonged the duration of hexobarbital-induced sleep, and increased amphetamine-induced hyperactivity. Locomotor agitation after octopamine injection was inhibited by phenoxybenzamine and yohimbine in a dose of 10 mg/kg i.p."}
{"id": "PMID:228530", "title": "Dynamics of beta adrenoceptor induced amylase release and cyclic AMP accumulation in the guinea pig submandibular gland.", "content": "The dynamics of amylase release from the guinea pig submandibular gland were studied in vitro by applying a multi-channel microperfusion set. This technique makes it possible to measure time related enzyme release more accurately and to take samples of perifused tissue at short intervals. Stimulation of the beta-adrenoceptor with norepinephrine gives rise to a rapid initial enzyme discharge, detectable within 15 s. Administration of propranolol inhibits enzyme release, which is not restored after removal of the agent. Simultaneous measurements of tissue cyclic AMP during norepinephrine stimulation at various time intervals display a significant increase of cAMP as early as 15 s after stimulation of secretion. This increase of cAMP thus coincides with the discharge of amylase. In addition, cAMP continuously accumulates during 30 min of norepinephrine perifusion of the slices. The present study describes a valuable tool with high sensitivity for visualizing the relations between enzyme secretion from the salivary gland and the intracellular biochemical processes. The data obtained further indicate a close correlation between amylase and cAMP during the initial phase of enzyme discharge.", "contents": "Dynamics of beta adrenoceptor induced amylase release and cyclic AMP accumulation in the guinea pig submandibular gland. The dynamics of amylase release from the guinea pig submandibular gland were studied in vitro by applying a multi-channel microperfusion set. This technique makes it possible to measure time related enzyme release more accurately and to take samples of perifused tissue at short intervals. Stimulation of the beta-adrenoceptor with norepinephrine gives rise to a rapid initial enzyme discharge, detectable within 15 s. Administration of propranolol inhibits enzyme release, which is not restored after removal of the agent. Simultaneous measurements of tissue cyclic AMP during norepinephrine stimulation at various time intervals display a significant increase of cAMP as early as 15 s after stimulation of secretion. This increase of cAMP thus coincides with the discharge of amylase. In addition, cAMP continuously accumulates during 30 min of norepinephrine perifusion of the slices. The present study describes a valuable tool with high sensitivity for visualizing the relations between enzyme secretion from the salivary gland and the intracellular biochemical processes. The data obtained further indicate a close correlation between amylase and cAMP during the initial phase of enzyme discharge."}
{"id": "PMID:228527", "title": "The gliovascular interphase in irradiated brain tissue. Electron microscopic investigations on location of specific phosphatases.", "content": "In the brains of rats exposed to a dose of 800 rads of gammma radiation the location of phosphatases hydrolysing the following phosphate esters: adenosinetriphosphate (ATP), cytidinetriphosphate (CTP), guanosinetriphosphate (GTP) and inosinediphosphate (IDP) was determined in the ultramicroscopic structures. Changes were observed in their location in the gliovascular interphase. Early after the exposure (6 hours) the activity of specific phosphatases decreased in brain capillaries, then (48 hours) the reaction product disappeared from the basal membrane of the capillaries and appeared in the endothelium. Later (72 hours -- 7 days) the intensity of the reaction increased in the processes of the astrocytes adhering to the capillary. These changes took place concomitantly with an increase in the permeability of the blood-brain barrier and suggested that specific phosphatases participate in the barrier mechanisms.", "contents": "The gliovascular interphase in irradiated brain tissue. Electron microscopic investigations on location of specific phosphatases. In the brains of rats exposed to a dose of 800 rads of gammma radiation the location of phosphatases hydrolysing the following phosphate esters: adenosinetriphosphate (ATP), cytidinetriphosphate (CTP), guanosinetriphosphate (GTP) and inosinediphosphate (IDP) was determined in the ultramicroscopic structures. Changes were observed in their location in the gliovascular interphase. Early after the exposure (6 hours) the activity of specific phosphatases decreased in brain capillaries, then (48 hours) the reaction product disappeared from the basal membrane of the capillaries and appeared in the endothelium. Later (72 hours -- 7 days) the intensity of the reaction increased in the processes of the astrocytes adhering to the capillary. These changes took place concomitantly with an increase in the permeability of the blood-brain barrier and suggested that specific phosphatases participate in the barrier mechanisms."}
{"id": "PMID:228542", "title": "Abdominal CT in the evaluation of small cell carcinoma of the lung.", "content": "Upper abdominal CT scans were performed on 45 consecutive patients with biopsy proven but previously untreated small cell carcinoma of the lung. Evidence of metastases was found in 16 (36%) patients. The most common site of metastases was the liver (27%). CT had a sensitivity of 88% and specificity of 94% as compared with biopsy results. Evidence of retroperitoneal metastases was found in seven (16%) patients.", "contents": "Abdominal CT in the evaluation of small cell carcinoma of the lung. Upper abdominal CT scans were performed on 45 consecutive patients with biopsy proven but previously untreated small cell carcinoma of the lung. Evidence of metastases was found in 16 (36%) patients. The most common site of metastases was the liver (27%). CT had a sensitivity of 88% and specificity of 94% as compared with biopsy results. Evidence of retroperitoneal metastases was found in seven (16%) patients."}
{"id": "PMID:228545", "title": "Expression of monocytic--histiocytic cytochemical markers in epithelial neoplasia.", "content": "The diagnosis of malignant histiocytosis is usually based upon typical light microscopic features of the neoplasm. Supplementary cytochemical and immunologic features have been suggested as typical of malignant histiocytosis. The present study was prompted by an unusual erythropagocytic hepatocellular carcinoma having immunologic and cytochemical markers suggesting mononuclear phagocytic origin. Twenty-four neoplasms of unquestionable epithelial origin were prospectively evaluated for activity of alpha-naphthyl acetate esterase, a cytochemical marker useful in distinguishing between the non-Hodgkin's lymphomas and malignant histiocytosis. The epithelial tumors represented a broad spectrum of tissue origins and consistently demonstrated alpha-naphthyl acetate esterase activity. Thus, erythrophagocytosis and alpha-naphthyl acetate esterase positivity may be misleading in the unusual instance in which the histopathologic differential diagnosis includes malignant histiocytosis and epithelial neoplasia. Ultrastructural assessment is useful in the exclusion of poorly differentiated carcinoma.", "contents": "Expression of monocytic--histiocytic cytochemical markers in epithelial neoplasia. The diagnosis of malignant histiocytosis is usually based upon typical light microscopic features of the neoplasm. Supplementary cytochemical and immunologic features have been suggested as typical of malignant histiocytosis. The present study was prompted by an unusual erythropagocytic hepatocellular carcinoma having immunologic and cytochemical markers suggesting mononuclear phagocytic origin. Twenty-four neoplasms of unquestionable epithelial origin were prospectively evaluated for activity of alpha-naphthyl acetate esterase, a cytochemical marker useful in distinguishing between the non-Hodgkin's lymphomas and malignant histiocytosis. The epithelial tumors represented a broad spectrum of tissue origins and consistently demonstrated alpha-naphthyl acetate esterase activity. Thus, erythrophagocytosis and alpha-naphthyl acetate esterase positivity may be misleading in the unusual instance in which the histopathologic differential diagnosis includes malignant histiocytosis and epithelial neoplasia. Ultrastructural assessment is useful in the exclusion of poorly differentiated carcinoma."}
{"id": "PMID:228546", "title": "Persistent falsely positive rapid tests for infectious mononucleosis. Report of five cases with four--six-year follow-up data.", "content": "In many laboratories, rapid slide tests incorporating differential absorption have replaced heterophil antibody tube tests in the investigation of suspect infectious mononucleosis. The present report describes serologic data from five individuals whose Monospot tests remained falsely positive for four years or more without other evidence of infectious mononucleosis or underlying disease states. Three of the five had never been infected with the Epstein-Barr virus. All five had negative results when studied with the ox cell hemolysin and the horse cell differential absorption tube tests. False-positive test results have also been encountered in healthy controls, as frequently as in patients with underlying disease states. The authors are unable to attach any clinical significance to the findings of an isolated falsely positive Monospot test even when it persists for many months or years.", "contents": "Persistent falsely positive rapid tests for infectious mononucleosis. Report of five cases with four--six-year follow-up data. In many laboratories, rapid slide tests incorporating differential absorption have replaced heterophil antibody tube tests in the investigation of suspect infectious mononucleosis. The present report describes serologic data from five individuals whose Monospot tests remained falsely positive for four years or more without other evidence of infectious mononucleosis or underlying disease states. Three of the five had never been infected with the Epstein-Barr virus. All five had negative results when studied with the ox cell hemolysin and the horse cell differential absorption tube tests. False-positive test results have also been encountered in healthy controls, as frequently as in patients with underlying disease states. The authors are unable to attach any clinical significance to the findings of an isolated falsely positive Monospot test even when it persists for many months or years."}
{"id": "PMID:228547", "title": "The effect of tocopherol on high-density lipoprotein cholesterol. A clinical observation.", "content": "A significant redistribution of cholesterol in lipoproteins following ingestion of large doses of D,L-alpha tocopherol (vitamin E) is documented. In persons with decreased high-density lipoprotein (HDL) cholesterol a complex response occurs, which includes cholesterol redistribution in favor of the HDL fraction, with decreases in very-low-density lipoprotein (VLDL) levels and total triglycerides. The response was studied in five persons with average cholestrol distributions and five persons with cholesterol distributions associated with high risk of coronary heart disease. The mean elevation of the HDL cholesterol concentration in the former group was 168% of the initial value, while the latter group experienced post-therapy levels 375% of initial levels.", "contents": "The effect of tocopherol on high-density lipoprotein cholesterol. A clinical observation. A significant redistribution of cholesterol in lipoproteins following ingestion of large doses of D,L-alpha tocopherol (vitamin E) is documented. In persons with decreased high-density lipoprotein (HDL) cholesterol a complex response occurs, which includes cholesterol redistribution in favor of the HDL fraction, with decreases in very-low-density lipoprotein (VLDL) levels and total triglycerides. The response was studied in five persons with average cholestrol distributions and five persons with cholesterol distributions associated with high risk of coronary heart disease. The mean elevation of the HDL cholesterol concentration in the former group was 168% of the initial value, while the latter group experienced post-therapy levels 375% of initial levels."}
{"id": "PMID:228548", "title": "Pulmonary silicatosis. A case diagnosed by needle-aspiration biopsy and energy-dispersive x-ray analysis.", "content": "The diagnosis of silicatosis was made by observing birefringent crystals in needle-aspiration biopsy specimens of bilateral basilar pulmonary masses in a clay worker, initially suspected of having metastatic neoplasm. Subsequently the crystals were examined by scanning electron microscopy and energy-dispersive x-ray analysis, which gave supportive evidence for their silicate composition. This experience indicates that needle-aspiration biopsy in conjunction with scanning electron microscopy and energy-dispersive x-ray analysis may be used in the diagnosis of benign pulmonary diseases, especially those of the inhalational fibrogenic variety.", "contents": "Pulmonary silicatosis. A case diagnosed by needle-aspiration biopsy and energy-dispersive x-ray analysis. The diagnosis of silicatosis was made by observing birefringent crystals in needle-aspiration biopsy specimens of bilateral basilar pulmonary masses in a clay worker, initially suspected of having metastatic neoplasm. Subsequently the crystals were examined by scanning electron microscopy and energy-dispersive x-ray analysis, which gave supportive evidence for their silicate composition. This experience indicates that needle-aspiration biopsy in conjunction with scanning electron microscopy and energy-dispersive x-ray analysis may be used in the diagnosis of benign pulmonary diseases, especially those of the inhalational fibrogenic variety."}
{"id": "PMID:228549", "title": "Extrarenal Wilms' tumor.", "content": "Extrarenal Wilms' tumor is a rare entity usually seen as a mass in the retroperitoneal area. It may surround and distort otherwise normal kidneys and ureters. Like many other abdominal masses, its true nature remains uncertain until microscopic examination has been performed after surgery. The tumors appear to behave clinically like intrarenal Wilms' tumors, though in the cases reviewed there was a relatively higher incidence in older patients. The prognosis of extrarenal Wilms' tumor is difficult to evaluate due to the small numbers of cases reported and the differing tumor therapy used. However, those cases treated most recently appear to have a good response to therapy.", "contents": "Extrarenal Wilms' tumor. Extrarenal Wilms' tumor is a rare entity usually seen as a mass in the retroperitoneal area. It may surround and distort otherwise normal kidneys and ureters. Like many other abdominal masses, its true nature remains uncertain until microscopic examination has been performed after surgery. The tumors appear to behave clinically like intrarenal Wilms' tumors, though in the cases reviewed there was a relatively higher incidence in older patients. The prognosis of extrarenal Wilms' tumor is difficult to evaluate due to the small numbers of cases reported and the differing tumor therapy used. However, those cases treated most recently appear to have a good response to therapy."}
{"id": "PMID:228550", "title": "Fabry's disease in a black kindred.", "content": "In a 16-member black kindred with Fabry's disease, four hemizygous males had plasma alpha-galactosidase levels less than 6% and seven heterozygous females had plasma alpha-galactosidase levels between 10% and 50% of normal. A 16-year-old index male had hypertension with left ventricular hypertrophy, abnormal renal function, tortuous retinal veins, \"myelin\" inclusions in bone marrow macrophages, and intraepithelial inclusion bodies in the kidney. Scrotal angiectasia developed a year after diagnosis. The three other affected males had left ventricular hypertrophy and retinal vein tortuosity. Of the seven carrier females, five had frequent headaches, four had retinal vessel changes, three had proteinuria with normal renal function, and two had bundle-branch blocks on ECGs. There was no deuteranomalopia in this family, although the inheritance pattern of the Fabry gene is X-linked recessive.", "contents": "Fabry's disease in a black kindred. In a 16-member black kindred with Fabry's disease, four hemizygous males had plasma alpha-galactosidase levels less than 6% and seven heterozygous females had plasma alpha-galactosidase levels between 10% and 50% of normal. A 16-year-old index male had hypertension with left ventricular hypertrophy, abnormal renal function, tortuous retinal veins, \"myelin\" inclusions in bone marrow macrophages, and intraepithelial inclusion bodies in the kidney. Scrotal angiectasia developed a year after diagnosis. The three other affected males had left ventricular hypertrophy and retinal vein tortuosity. Of the seven carrier females, five had frequent headaches, four had retinal vessel changes, three had proteinuria with normal renal function, and two had bundle-branch blocks on ECGs. There was no deuteranomalopia in this family, although the inheritance pattern of the Fabry gene is X-linked recessive."}
{"id": "PMID:228552", "title": "Amebic liver abscess. Report of a case presenting with nonreactive serologic tests for Entamoeba histolytica.", "content": "We present a patient with an acute amebic liver abscess with nonreactive serologic tests. Motile hematophagous trophozoites of Entamoeba histolytica were seen microscopically in scrapings from the wall of the abscess. Postoperative serologies revealed rapidly rising then falling titers by SAFA and IHA antibody assays. Serologic tests for amebiasis may be reative in greater than 95% of patients with invasive amebiasis. Nevertheless, a reactive serologic test should not be relied upon exclusively to establish the diagnosis. Sequential serologic testing and surgical intervention to obtain material for microscopic examination, gram stain and bacteriologic culture are warranted in patients with hepatic abscess and nonreactive serologic tests for antibodies to E. histolytica.", "contents": "Amebic liver abscess. Report of a case presenting with nonreactive serologic tests for Entamoeba histolytica. We present a patient with an acute amebic liver abscess with nonreactive serologic tests. Motile hematophagous trophozoites of Entamoeba histolytica were seen microscopically in scrapings from the wall of the abscess. Postoperative serologies revealed rapidly rising then falling titers by SAFA and IHA antibody assays. Serologic tests for amebiasis may be reative in greater than 95% of patients with invasive amebiasis. Nevertheless, a reactive serologic test should not be relied upon exclusively to establish the diagnosis. Sequential serologic testing and surgical intervention to obtain material for microscopic examination, gram stain and bacteriologic culture are warranted in patients with hepatic abscess and nonreactive serologic tests for antibodies to E. histolytica."}
{"id": "PMID:228553", "title": "Autoimmune hemolytic anemia and carcinoma: an unusual association.", "content": "Four patients with Coombs'-positive hemolytic anemia associated with carcinoma are presented and compared to 12 previously described patients. These patients commonly seek medical attention for symptoms of anemia rather than for complaints due to the tumor mass. The physician should particularly evaluate for an underlying carcinoma when a patient over the age of 60 years presents with autoimmune hemolytic anemia. Autoimmune hemolytic disease has been demonstrated in patients with a wide variety of tumors, including squamous cell carcinomas, adenocarcinomas, hypernephromas, oat cell carcinomas and a seminoma. Corticosteroid treatment is less effective in autoimmune hemolytic disease associated with carcinoma than in idiopathic autoimmune hemolysis. Tumor extirpation in patients with localized neoplastic disease may abolish the autoimmune hemolytic anemia. Control of the carcinoma through irradiation and chemotherapy together with corticosteroid therapy and/or splenectomy lessened the anemia in some patients. The positive Coombs' test may revert to negative with tumor excision or control. Subsequently, the positivity of the Coombs' reaction may provide a clue to recurrent neoplastic activity. The pathogenic mechanism underlying the association between carcinoma and autoimmune hemolytic disease is poorly understood.", "contents": "Autoimmune hemolytic anemia and carcinoma: an unusual association. Four patients with Coombs'-positive hemolytic anemia associated with carcinoma are presented and compared to 12 previously described patients. These patients commonly seek medical attention for symptoms of anemia rather than for complaints due to the tumor mass. The physician should particularly evaluate for an underlying carcinoma when a patient over the age of 60 years presents with autoimmune hemolytic anemia. Autoimmune hemolytic disease has been demonstrated in patients with a wide variety of tumors, including squamous cell carcinomas, adenocarcinomas, hypernephromas, oat cell carcinomas and a seminoma. Corticosteroid treatment is less effective in autoimmune hemolytic disease associated with carcinoma than in idiopathic autoimmune hemolysis. Tumor extirpation in patients with localized neoplastic disease may abolish the autoimmune hemolytic anemia. Control of the carcinoma through irradiation and chemotherapy together with corticosteroid therapy and/or splenectomy lessened the anemia in some patients. The positive Coombs' test may revert to negative with tumor excision or control. Subsequently, the positivity of the Coombs' reaction may provide a clue to recurrent neoplastic activity. The pathogenic mechanism underlying the association between carcinoma and autoimmune hemolytic disease is poorly understood."}
{"id": "PMID:228554", "title": "Angiotensin-converting enzyme: serum levels during normal pregnancy.", "content": "ACE activity of the serum of 52 normal pregnant women was measured in vitro under conditions of substrate saturation with Hip-His-Leu as substrate. The product His-Leu was measured by fluorimetry after reaction with o-phthaldehyde. ACE activity (nmol/min/ml serum) was 30.6 +/- 7.8, 28.8 +/- 7.4, and 30.9 +/- 8.2 for the first, second, and third trimester of pregnancy, respectively. No statistically significant differences (p greater than 0.05) in ACE activity were detected among the three trimesters of normal pregnancy with either serum volume or serum protein as reference value. These values are within the range reported by Friedland and Silverstein13 for 51 male and seven female healthy blood bank donors. We conclude that the evolution of normal pregnancy does not significantly modify the levels of ACE in peripheral blood serum.", "contents": "Angiotensin-converting enzyme: serum levels during normal pregnancy. ACE activity of the serum of 52 normal pregnant women was measured in vitro under conditions of substrate saturation with Hip-His-Leu as substrate. The product His-Leu was measured by fluorimetry after reaction with o-phthaldehyde. ACE activity (nmol/min/ml serum) was 30.6 +/- 7.8, 28.8 +/- 7.4, and 30.9 +/- 8.2 for the first, second, and third trimester of pregnancy, respectively. No statistically significant differences (p greater than 0.05) in ACE activity were detected among the three trimesters of normal pregnancy with either serum volume or serum protein as reference value. These values are within the range reported by Friedland and Silverstein13 for 51 male and seven female healthy blood bank donors. We conclude that the evolution of normal pregnancy does not significantly modify the levels of ACE in peripheral blood serum."}
{"id": "PMID:228555", "title": "Establishment and characterization of a new endometrial cancer cell line (SCRC-1).", "content": "A new human endometrial cell line, SCRC-1, has been established from a uterine adenocarcinoma. During a period of 57 weeks in culture, the SCRC-1 cells have been passaged over 100 times. Cultures have an epitheloid morphology, high mitotic activity, and a tendency to form multiple cell layers. The cells are polygonal and are arranged in pavement-like fashion. Most have multiple nucleoli, some are multinucleated, and all have heavily vacuolated cytoplasm. Pretreatment with iododeoxyuridine did not reveal viral markers by cocultivation or immunofluorescence techniques. Karyologic studies indicate that the SCRC11 cell line is essentially diploid with a small subpopulation of tetraploid cells. Over a period of 20 weeks, 1 of 14 athymic nude mice inoculated with SCRC-1 cells developed a tumor which histologically closely resembled the original human tumor. Cells were subsequently propagated from this tumor and the resulting epitheloid-like cell line was designated SCRC-1, Tu 1.", "contents": "Establishment and characterization of a new endometrial cancer cell line (SCRC-1). A new human endometrial cell line, SCRC-1, has been established from a uterine adenocarcinoma. During a period of 57 weeks in culture, the SCRC-1 cells have been passaged over 100 times. Cultures have an epitheloid morphology, high mitotic activity, and a tendency to form multiple cell layers. The cells are polygonal and are arranged in pavement-like fashion. Most have multiple nucleoli, some are multinucleated, and all have heavily vacuolated cytoplasm. Pretreatment with iododeoxyuridine did not reveal viral markers by cocultivation or immunofluorescence techniques. Karyologic studies indicate that the SCRC11 cell line is essentially diploid with a small subpopulation of tetraploid cells. Over a period of 20 weeks, 1 of 14 athymic nude mice inoculated with SCRC-1 cells developed a tumor which histologically closely resembled the original human tumor. Cells were subsequently propagated from this tumor and the resulting epitheloid-like cell line was designated SCRC-1, Tu 1."}
{"id": "PMID:228556", "title": "Necrotizing retinitis caused by opportunistic virus infection in a patient with Hodgkin's disease.", "content": "A 33-year-old woman with Hodgkin's disease developed a painless progressive loss of vision in both eyes. Despite an ophthalmoscopic appearance of white-yellow retinal necrosis and retinal hemorrhage similar to that described with Hodgkin's disease, no sign of the disorder was found at autopsy. Instead, widespread evidence of Herpesviridae family virus infection was present in several organs, including the retinas. Opportunistic infection, including herpes simplex and cytomegalovirus, should be considered when retinitis complicates Hodgkin's disease.", "contents": "Necrotizing retinitis caused by opportunistic virus infection in a patient with Hodgkin's disease. A 33-year-old woman with Hodgkin's disease developed a painless progressive loss of vision in both eyes. Despite an ophthalmoscopic appearance of white-yellow retinal necrosis and retinal hemorrhage similar to that described with Hodgkin's disease, no sign of the disorder was found at autopsy. Instead, widespread evidence of Herpesviridae family virus infection was present in several organs, including the retinas. Opportunistic infection, including herpes simplex and cytomegalovirus, should be considered when retinitis complicates Hodgkin's disease."}
{"id": "PMID:228557", "title": "Chronic keratoconjunctivitis associated with ocular adenovirus infection.", "content": "Adenovirus (types 3, 4, 5) was implicated as the etiologic agent in three cases of persistent keratoconjunctivitis. In two, virus was isolated 25 and 29 months after the onset of symptoms; the third patient has suffered intermittent flares of kerato-conjunctivitis since the initial isolation of virus 13 weeks after the onset of the disease. Such patients may represent a previously unsuspected source of adenovirus in the population. All were given corticosteroids topically. This treatment may have prolonged the adenoviral disease.", "contents": "Chronic keratoconjunctivitis associated with ocular adenovirus infection. Adenovirus (types 3, 4, 5) was implicated as the etiologic agent in three cases of persistent keratoconjunctivitis. In two, virus was isolated 25 and 29 months after the onset of symptoms; the third patient has suffered intermittent flares of kerato-conjunctivitis since the initial isolation of virus 13 weeks after the onset of the disease. Such patients may represent a previously unsuspected source of adenovirus in the population. All were given corticosteroids topically. This treatment may have prolonged the adenoviral disease."}
{"id": "PMID:228559", "title": "Predictors of community tenure of discharged state hospital patients.", "content": "Community treatment of formerly hospitalized patients is in need of evaluation. The authors evaluated an aftercare program by examining its effect on the amount of time spent in the community by patients discharged from a state mental hospital. They assessed the impact of specific intervention in the areas of housing, employment, finances, psychiatric treatment, medication, and leisure. They conclude that assistance during the transition from the hospital to the community prolonged community tenure, that intervention in the areas of housing, finances, and medication was especially important, and that treatment in the community increased the amount of time spent in the community during the first 6 months after discharge.", "contents": "Predictors of community tenure of discharged state hospital patients. Community treatment of formerly hospitalized patients is in need of evaluation. The authors evaluated an aftercare program by examining its effect on the amount of time spent in the community by patients discharged from a state mental hospital. They assessed the impact of specific intervention in the areas of housing, employment, finances, psychiatric treatment, medication, and leisure. They conclude that assistance during the transition from the hospital to the community prolonged community tenure, that intervention in the areas of housing, finances, and medication was especially important, and that treatment in the community increased the amount of time spent in the community during the first 6 months after discharge."}
{"id": "PMID:228561", "title": "Failure of indicator bacteria to reflect the occurrence of enteroviruses in marine waters.", "content": "The results of several studies conducted along the upper Texas Gulf coast, where a substantial amount of quantitative virological data were collected, are compared to bacteriological indicators and other environmental factors on a statistical basis. Variables common to all these studies were anlayzed by multivariate regression. Although multivariate analysis indicated that the number of viruses detected in water was related to rainfall, salinity, and total coliforms in the water, the amount of variation in the number of viruses accounted for by these factors was not large enough to make them good predictors. Enteroviruses were detected 43 per cent of the time in recreational waters considered acceptable as judged by coliform standards, and 44 per cent of the time when judged by fecal coliform standards. Enteroviruses were detected 35 per cent of the time in waters which met acceptable standards for shellfish-harvesting. Our failure to correlate the occurrence of enteroviruses in marine waters with indicator bacteria, and the frequent occurrence of enteroviruses in water which met current bacteriological standards, indicates that these standards do not reflect the occurrence of enteroviruses, and perhaps other human pathogenic viruses, in marine waters.", "contents": "Failure of indicator bacteria to reflect the occurrence of enteroviruses in marine waters. The results of several studies conducted along the upper Texas Gulf coast, where a substantial amount of quantitative virological data were collected, are compared to bacteriological indicators and other environmental factors on a statistical basis. Variables common to all these studies were anlayzed by multivariate regression. Although multivariate analysis indicated that the number of viruses detected in water was related to rainfall, salinity, and total coliforms in the water, the amount of variation in the number of viruses accounted for by these factors was not large enough to make them good predictors. Enteroviruses were detected 43 per cent of the time in recreational waters considered acceptable as judged by coliform standards, and 44 per cent of the time when judged by fecal coliform standards. Enteroviruses were detected 35 per cent of the time in waters which met acceptable standards for shellfish-harvesting. Our failure to correlate the occurrence of enteroviruses in marine waters with indicator bacteria, and the frequent occurrence of enteroviruses in water which met current bacteriological standards, indicates that these standards do not reflect the occurrence of enteroviruses, and perhaps other human pathogenic viruses, in marine waters."}
{"id": "PMID:228562", "title": "Serological markers for hepatitis types A and B among U.S. Arym soldiers, Germany.", "content": "Viral hepatitis rates among U.S. Army soldiers in Europe have been found to be two to three times higher than corresponding rates for soldiers stationed in the U.S. Sera from 89 per cent of a representative Army unit with 865 members and a known hepatitis problem were tested for HBsAg, anti-HBs, anti-HBc, and anti-HA. The prevalence of HB markers was 20 per cent, and hepatitis A antibody was present in 25 per cent. A six-month follow-up, conducted on 260 individuals initially negative for all four tests, revealed that 11 of these were now HB seropositive, whereas none had seroconverted to anti-HA positive. The HB virus was the principal agent responsible for hepatitis in the unit surveyed.", "contents": "Serological markers for hepatitis types A and B among U.S. Arym soldiers, Germany. Viral hepatitis rates among U.S. Army soldiers in Europe have been found to be two to three times higher than corresponding rates for soldiers stationed in the U.S. Sera from 89 per cent of a representative Army unit with 865 members and a known hepatitis problem were tested for HBsAg, anti-HBs, anti-HBc, and anti-HA. The prevalence of HB markers was 20 per cent, and hepatitis A antibody was present in 25 per cent. A six-month follow-up, conducted on 260 individuals initially negative for all four tests, revealed that 11 of these were now HB seropositive, whereas none had seroconverted to anti-HA positive. The HB virus was the principal agent responsible for hepatitis in the unit surveyed."}
{"id": "PMID:228564", "title": "Milk lipid absorption and chylomicron production in the suckling rat.", "content": "Structural correlates of milk lipid absorption and chylomicron production were studied in 10-day-old suckled rats. The gastric and duodenal contents and duodenal mucosae were examined with the light and electron microscopes. In the gastric lumen the milk lipid globule cores were smooth, circular and uniformly electron opaque. Many membranes and lamellar structures with a trilaminar and multilamellar appearance were adherent to the peripheries of the cores. In the central duodenal lumen the milk lipid globule cores were also smooth, circular and uniformly electron opaque. Very few milk lipid globules in the duodenal lumen showed adherent membranes or lamellae. Membrane fragments and lamellae were present in the lumen separate from the milk lipid globules. In the duodenal lumen between villi the milk lipid globules had multiple electron lucent indentations of the core. It is believed that the irregular peripheries of the milk lipid globule cores are the result of lipolysis within the duodenal lumen acting at the milk lipid globule surface. This lipolysis of triacylglycerol would produce amphiphilic lipids which may result in the electron lucent spaces at the milk lipid globule periphery. The absorptive epithelial cells along the length of the duodenal villus varied in structure relative to their position at the tip, middle, or base of the villus. Typical mid-villus epithelial cells contained lipid droplets averaging 0.3-micrometer diameter in the smooth and rough endoplasmic reticulum and in Golgi complexes in the apical cytoplasm. Villus tip and villus base cells contained large lipid droplets between 7-16 micrometers. Only a few 0.3-micrometer lipid droplets were present within these cells. These large lipid droplets appeared to be accumulations of triacylglycerol present in the apical cytoplasm associated with lamellar and membranous structures. Numerous chylomicrons were present between epithelial cells located in the middle region of the villus while significantly fewer chylomicrons were seen between epithelial cells at the tip and base of the villus. These observations suggest that the cells at the middle of the duodenal villus of suckling rats were more efficient in the production of chylomicron triacylglycerol derived from incoming milk triacylglycerol than cells at the tip and base of the villus.", "contents": "Milk lipid absorption and chylomicron production in the suckling rat. Structural correlates of milk lipid absorption and chylomicron production were studied in 10-day-old suckled rats. The gastric and duodenal contents and duodenal mucosae were examined with the light and electron microscopes. In the gastric lumen the milk lipid globule cores were smooth, circular and uniformly electron opaque. Many membranes and lamellar structures with a trilaminar and multilamellar appearance were adherent to the peripheries of the cores. In the central duodenal lumen the milk lipid globule cores were also smooth, circular and uniformly electron opaque. Very few milk lipid globules in the duodenal lumen showed adherent membranes or lamellae. Membrane fragments and lamellae were present in the lumen separate from the milk lipid globules. In the duodenal lumen between villi the milk lipid globules had multiple electron lucent indentations of the core. It is believed that the irregular peripheries of the milk lipid globule cores are the result of lipolysis within the duodenal lumen acting at the milk lipid globule surface. This lipolysis of triacylglycerol would produce amphiphilic lipids which may result in the electron lucent spaces at the milk lipid globule periphery. The absorptive epithelial cells along the length of the duodenal villus varied in structure relative to their position at the tip, middle, or base of the villus. Typical mid-villus epithelial cells contained lipid droplets averaging 0.3-micrometer diameter in the smooth and rough endoplasmic reticulum and in Golgi complexes in the apical cytoplasm. Villus tip and villus base cells contained large lipid droplets between 7-16 micrometers. Only a few 0.3-micrometer lipid droplets were present within these cells. These large lipid droplets appeared to be accumulations of triacylglycerol present in the apical cytoplasm associated with lamellar and membranous structures. Numerous chylomicrons were present between epithelial cells located in the middle region of the villus while significantly fewer chylomicrons were seen between epithelial cells at the tip and base of the villus. These observations suggest that the cells at the middle of the duodenal villus of suckling rats were more efficient in the production of chylomicron triacylglycerol derived from incoming milk triacylglycerol than cells at the tip and base of the villus."}
{"id": "PMID:228565", "title": "Ultrastructural changes in Leydig cells of streptozotocin-induced diabetic rats.", "content": "Hyperglycemia (experimental diabetes) was induced in adult male rats by destruction of the pancreatic beta cells with a single intravenous injection of streptozotocin (STZ). Testes from diabetic, from insulin-treated diabetic, and from sham-injected normal rats were fxed by vascular perfusion. The fine structure of Leydig cells was examined at two, three, and four weeks after the STZ injection in the untreated diabetic animals, and at four weeks in the controls and insulin-treated diabetic rats. A number of morphological changes was observed in Leydig cells of untreated diabetic animals. Most obvious of these was an accumulation of lipid droplets, not normally present in Leydig cells in adults of this species. Smooth endoplasmic reticulum (SER) was markedly reduced in Leydig cells of the hyperglycemic rats. Several types of intracellular bodies were seen exclusively in Leydig cells of the untreated diabetic animals. Many resembled secondary lysosomes or dense bodies, while others appeared to be autophagic vacuoles. In addition, a small, granule-containing lamellar structure was seen either within a typical dense body or free in the cytoplasm. Myelin-like structures were commonly observed within the cytoplasm of the Leydig cell or within mitochondria. The appearance of the mitochondria in diabetic rats was otherwise normal. The extracellular spaces surrounding Leydig cells from untreated hyperglycemic rats also contained large accumulations of myelin-like material. These structural changes appear to be direct consequences of the diabetic state of the animals, since the ultrastructure of insulin-treated diabetic rats did not differ from that of the controls. These findings may reflect an alteration or breakdown of Leydig cell components normally involved in the synthesis of androgen, and correlate with previous reports of lowered circulating levels of testosterone in diabetic rats.", "contents": "Ultrastructural changes in Leydig cells of streptozotocin-induced diabetic rats. Hyperglycemia (experimental diabetes) was induced in adult male rats by destruction of the pancreatic beta cells with a single intravenous injection of streptozotocin (STZ). Testes from diabetic, from insulin-treated diabetic, and from sham-injected normal rats were fxed by vascular perfusion. The fine structure of Leydig cells was examined at two, three, and four weeks after the STZ injection in the untreated diabetic animals, and at four weeks in the controls and insulin-treated diabetic rats. A number of morphological changes was observed in Leydig cells of untreated diabetic animals. Most obvious of these was an accumulation of lipid droplets, not normally present in Leydig cells in adults of this species. Smooth endoplasmic reticulum (SER) was markedly reduced in Leydig cells of the hyperglycemic rats. Several types of intracellular bodies were seen exclusively in Leydig cells of the untreated diabetic animals. Many resembled secondary lysosomes or dense bodies, while others appeared to be autophagic vacuoles. In addition, a small, granule-containing lamellar structure was seen either within a typical dense body or free in the cytoplasm. Myelin-like structures were commonly observed within the cytoplasm of the Leydig cell or within mitochondria. The appearance of the mitochondria in diabetic rats was otherwise normal. The extracellular spaces surrounding Leydig cells from untreated hyperglycemic rats also contained large accumulations of myelin-like material. These structural changes appear to be direct consequences of the diabetic state of the animals, since the ultrastructure of insulin-treated diabetic rats did not differ from that of the controls. These findings may reflect an alteration or breakdown of Leydig cell components normally involved in the synthesis of androgen, and correlate with previous reports of lowered circulating levels of testosterone in diabetic rats."}
{"id": "PMID:228568", "title": "Influence of environment on adrenal cortical response to ACTH stimulation in clinically normal dogs.", "content": "Effect of testing environment on adrenal cortical responses to an injection of ACTH in clinically normal dogs was examined in three locations, presumably of increasing order of stress elicitation: in a home; veterinary hospital (VH), 4 hours in a cage; and VH, overnight in a cage. Basal cortisol (hydrocortisone) values for plasma were significantly lower (P less than 0.001) for the home group (1.8 microgram/dl) when compared with values for the VH, 4-hour cage (3.8 microgram/dl) or the VH, overnight cage (3.9 microgram/dl) groups. However, significant differences (P greater than 0.05) were not observed 2 hours after ACTH admininstration for the home group (13.7 microgram/dl); VH, 4-hour cage group (14.8 microgram/dl); or VH, overnight cage group (16.0 microgram/dl). Responses of individual dogs were consistent (P less than 0.005). The testing environment did not markedly affect results of adrenal cortical function tests for dogs when ACTH stimulation was utilized. The response of dogs to ACTH, as monitored by immunologic assay techniques (competitive protein-binding assay or radioimmunoassay), was consistent and was useful as a diagnostic aid for adrenal malfunction.", "contents": "Influence of environment on adrenal cortical response to ACTH stimulation in clinically normal dogs. Effect of testing environment on adrenal cortical responses to an injection of ACTH in clinically normal dogs was examined in three locations, presumably of increasing order of stress elicitation: in a home; veterinary hospital (VH), 4 hours in a cage; and VH, overnight in a cage. Basal cortisol (hydrocortisone) values for plasma were significantly lower (P less than 0.001) for the home group (1.8 microgram/dl) when compared with values for the VH, 4-hour cage (3.8 microgram/dl) or the VH, overnight cage (3.9 microgram/dl) groups. However, significant differences (P greater than 0.05) were not observed 2 hours after ACTH admininstration for the home group (13.7 microgram/dl); VH, 4-hour cage group (14.8 microgram/dl); or VH, overnight cage group (16.0 microgram/dl). Responses of individual dogs were consistent (P less than 0.005). The testing environment did not markedly affect results of adrenal cortical function tests for dogs when ACTH stimulation was utilized. The response of dogs to ACTH, as monitored by immunologic assay techniques (competitive protein-binding assay or radioimmunoassay), was consistent and was useful as a diagnostic aid for adrenal malfunction."}
{"id": "PMID:228569", "title": "Failure of neuromuscular transmission after complete nerve section in the dog.", "content": "After the ulnar nerve was surgically transected, nerve conduction velocity in the distal segment and the evoked motor unit potential (EMUP) from the interosseous muscle were recorded until neuromuscular transmission failed. In five of the six dogs in the experiment, functional conduction ceased by 4.8 days, as determined by failure of both proximal and distal stimulation of the distal segment to evoke a muscle response. From the time of section until neuromuscular failure, the nerve conduction velocity remained unchanged. The amplitude of the EMUP from the interosseous muscle, however, decreased markedly during this time. Changes in other features of the EMUP are also presented. Fibrillation (denervation) potentials did not appear until the first day that muscle response could not be detected by stimulating the nerve. These data present a principle which would enable a determination of relative extent and progression of peripheral nerve damage.", "contents": "Failure of neuromuscular transmission after complete nerve section in the dog. After the ulnar nerve was surgically transected, nerve conduction velocity in the distal segment and the evoked motor unit potential (EMUP) from the interosseous muscle were recorded until neuromuscular transmission failed. In five of the six dogs in the experiment, functional conduction ceased by 4.8 days, as determined by failure of both proximal and distal stimulation of the distal segment to evoke a muscle response. From the time of section until neuromuscular failure, the nerve conduction velocity remained unchanged. The amplitude of the EMUP from the interosseous muscle, however, decreased markedly during this time. Changes in other features of the EMUP are also presented. Fibrillation (denervation) potentials did not appear until the first day that muscle response could not be detected by stimulating the nerve. These data present a principle which would enable a determination of relative extent and progression of peripheral nerve damage."}
{"id": "PMID:228572", "title": "Adenocarcinoma of the lung: recent results from the Veterans Administration Lung Group.", "content": "Adenocarcinoma has become the most common type of cancer of the lung. Its distinct natural history necessitates separation from the other cell types. Results from recent Veterans Administration Lung Group studies show that local-regional failure occurred in 59% of patients after irradiation for adenocarcinoma limited to the thorax. Data from 300 consecutive autopsies reveal that death was caused by intrathoracic complications of the tumor in 38%, and by metastases in 57% of patients. Adenocarcinoma has an intermediate risk of local and distant failure when compared to squamous and small-cell carcinoma. However, brain metastases are most frequent with adenocarcinoma. Preliminary results suggest that prophylactic brain irradiation decreases the frequency of brain metastases. Patients with adenocarcinoma are more likely than those with other cell types to have metastases only in the brain. Prophylactic brain irradiation may make the greatest contribution to improved survival in pateints with adenocarcinoma of the lung.", "contents": "Adenocarcinoma of the lung: recent results from the Veterans Administration Lung Group. Adenocarcinoma has become the most common type of cancer of the lung. Its distinct natural history necessitates separation from the other cell types. Results from recent Veterans Administration Lung Group studies show that local-regional failure occurred in 59% of patients after irradiation for adenocarcinoma limited to the thorax. Data from 300 consecutive autopsies reveal that death was caused by intrathoracic complications of the tumor in 38%, and by metastases in 57% of patients. Adenocarcinoma has an intermediate risk of local and distant failure when compared to squamous and small-cell carcinoma. However, brain metastases are most frequent with adenocarcinoma. Preliminary results suggest that prophylactic brain irradiation decreases the frequency of brain metastases. Patients with adenocarcinoma are more likely than those with other cell types to have metastases only in the brain. Prophylactic brain irradiation may make the greatest contribution to improved survival in pateints with adenocarcinoma of the lung."}
{"id": "PMID:228573", "title": "Lung cancer in chloromethyl ether workers.", "content": "During the period from 1948 to 71, some workers in a chemical plant were exposed to chloromethyl ethers in varying degrees and for varying durations. A historical cohort study of 1,446 male production employees from 1960 through 1975 showed both an increased risk of lung cancer as compared to that in the general population among 465 exposed workers and a dose-response relationship. Significantly increased risk occurred only among men with moderate and heavy chemical exposure. Smoking habit could account for some of the cases of lung cancer that developed in men with light chemical exposure and for cases among unexposed workers. Microscopic sections of most of the lung cancers were reviewed, and the results suggested that small-cell carcinoma was a specific response to inhalation of chloromethyl ethers.", "contents": "Lung cancer in chloromethyl ether workers. During the period from 1948 to 71, some workers in a chemical plant were exposed to chloromethyl ethers in varying degrees and for varying durations. A historical cohort study of 1,446 male production employees from 1960 through 1975 showed both an increased risk of lung cancer as compared to that in the general population among 465 exposed workers and a dose-response relationship. Significantly increased risk occurred only among men with moderate and heavy chemical exposure. Smoking habit could account for some of the cases of lung cancer that developed in men with light chemical exposure and for cases among unexposed workers. Microscopic sections of most of the lung cancers were reviewed, and the results suggested that small-cell carcinoma was a specific response to inhalation of chloromethyl ethers."}
{"id": "PMID:228579", "title": "[Presence of antibodies in human colostral secretory IgA against enteric commensal bacteria: biological implications (author's transl)].", "content": "Antisecretory component, anti-alpha, anti-mu and anti-Fc (gamma) fluorescent antibodies were used to detect the presence of immunoglobulins with antibody activity against enteric commensal bacteria in human colostrum and serum. Forty nine colostrum samples were studied; all of them displayed secretory IgA (sIgA) antibodies reacting with Bacteroides thetaiotaomicron, Clostridium perfringens and Escherichia coli serotype O141:H32 without any K antigen. The amount of sIgA antibodies was always related to the sIgA colostral concentration varying greatly from one patient to another. For the 3 lactating women studied, the colostrum sIgA antibodies were largely predominant as compared to the antibodies of other classes; in their sera, no antibody having the same anticommensal specificity was detected in the IgA fraction while these antibodies were found in IgM and IgG. Our results are incompatible with the existence of local antigenic stimulation, and the IgA transfer from serum into mammary secretion appears unlikely, but these results are perfectly compatible with the antigenic stimulation of gut associated lymphoid tissue and subsequent migration in mammary tissue.", "contents": "[Presence of antibodies in human colostral secretory IgA against enteric commensal bacteria: biological implications (author's transl)]. Antisecretory component, anti-alpha, anti-mu and anti-Fc (gamma) fluorescent antibodies were used to detect the presence of immunoglobulins with antibody activity against enteric commensal bacteria in human colostrum and serum. Forty nine colostrum samples were studied; all of them displayed secretory IgA (sIgA) antibodies reacting with Bacteroides thetaiotaomicron, Clostridium perfringens and Escherichia coli serotype O141:H32 without any K antigen. The amount of sIgA antibodies was always related to the sIgA colostral concentration varying greatly from one patient to another. For the 3 lactating women studied, the colostrum sIgA antibodies were largely predominant as compared to the antibodies of other classes; in their sera, no antibody having the same anticommensal specificity was detected in the IgA fraction while these antibodies were found in IgM and IgG. Our results are incompatible with the existence of local antigenic stimulation, and the IgA transfer from serum into mammary secretion appears unlikely, but these results are perfectly compatible with the antigenic stimulation of gut associated lymphoid tissue and subsequent migration in mammary tissue."}
{"id": "PMID:228578", "title": "[Attachment of a collagenolytic strain to its substrate (author's transl)].", "content": "The bacterial collagenolytic strain Acinetobacter sp. CRZV2 adheres to insoluble collagen fibers when this substrate is introduced into the growth medium. This attachment occurs during the exponential growth. Proteolytic enzymes such as pronase and trypsine activate the adherence of bacterial cells to collagen fibers.", "contents": "[Attachment of a collagenolytic strain to its substrate (author's transl)]. The bacterial collagenolytic strain Acinetobacter sp. CRZV2 adheres to insoluble collagen fibers when this substrate is introduced into the growth medium. This attachment occurs during the exponential growth. Proteolytic enzymes such as pronase and trypsine activate the adherence of bacterial cells to collagen fibers."}
{"id": "PMID:228587", "title": "The natural history of peripheral neuropathy in primary systemic amyloidosis.", "content": "The records of 31 patients with primary systemic amyloidosis and peripheral neuropathy seen during a 17-year period were analyzed to define the natural history of the neuropathy. Patients tended to be older men with a painful, distal, symmetrical sensorimotor neuropathy and prominent autonomic features. Loss of pain and temperature sensation was frequently more striking than loss of mechanoreception. Renal, cardiac, hematological, and gastrointestinal dysfunction often overshadowed the neuropathy. Clinical, neurophysiological, and histopathological studies pointed to axonal degeneration with predominant but not exclusive involvement of small myelinated and unmyelinated fibers. The neuropathy was progressive in all patients with or without treatment, but death was typically due to supervening medical complications.", "contents": "The natural history of peripheral neuropathy in primary systemic amyloidosis. The records of 31 patients with primary systemic amyloidosis and peripheral neuropathy seen during a 17-year period were analyzed to define the natural history of the neuropathy. Patients tended to be older men with a painful, distal, symmetrical sensorimotor neuropathy and prominent autonomic features. Loss of pain and temperature sensation was frequently more striking than loss of mechanoreception. Renal, cardiac, hematological, and gastrointestinal dysfunction often overshadowed the neuropathy. Clinical, neurophysiological, and histopathological studies pointed to axonal degeneration with predominant but not exclusive involvement of small myelinated and unmyelinated fibers. The neuropathy was progressive in all patients with or without treatment, but death was typically due to supervening medical complications."}
{"id": "PMID:228588", "title": "The TO strains of Theiler's viruses cause \"slow virus-like\" infections in mice.", "content": "Intracerebral inoculation of mice with tissue culture-adapted TO strains of Theiler's mouse encephalomyelitis viruses results in a clinical disease consisting of spastic paralysis due to demyelination after a lengthy incubation period. Thus, in effect, these ordinary picornaviruses are capable of causing a slow infection in their natural host, the mouse. In addition, through the use of tissue culture-adapted virus stocks, virus content in mouse tissues now can be accurately quantified by standard plaque assay.", "contents": "The TO strains of Theiler's viruses cause \"slow virus-like\" infections in mice. Intracerebral inoculation of mice with tissue culture-adapted TO strains of Theiler's mouse encephalomyelitis viruses results in a clinical disease consisting of spastic paralysis due to demyelination after a lengthy incubation period. Thus, in effect, these ordinary picornaviruses are capable of causing a slow infection in their natural host, the mouse. In addition, through the use of tissue culture-adapted virus stocks, virus content in mouse tissues now can be accurately quantified by standard plaque assay."}
{"id": "PMID:228589", "title": "Pupillary dysfunction in myasthenia gravis.", "content": "The constriction-dilation cycles of pupils exposed to a stationary, discrete slit-lamp beam were significantly prolonged in 25 myasthenic patients (1,060.4 +/- 45.8 msec) undergoing therapy with steroids, anticholinesterases, or both, compared to normal controls (801.9 +/- 8.6 msec) or subjects receiving steroids for nonneurological disease (860.9 +/- 14.9 msec). The duration of myasthenia correlated with the slowing of the cycle time. Myasthenia gravis may affect ectodermally derived smooth muscle or the autonomic neuromuscular junction or both, and not be restricted to the well-demonstrated alterations of neuromuscular junction in striated muscle of mesodermal origin. Alternatively, prolonged pupillary cycles could be attributed to dysfunction of central pathways of the pupillary light reflex.", "contents": "Pupillary dysfunction in myasthenia gravis. The constriction-dilation cycles of pupils exposed to a stationary, discrete slit-lamp beam were significantly prolonged in 25 myasthenic patients (1,060.4 +/- 45.8 msec) undergoing therapy with steroids, anticholinesterases, or both, compared to normal controls (801.9 +/- 8.6 msec) or subjects receiving steroids for nonneurological disease (860.9 +/- 14.9 msec). The duration of myasthenia correlated with the slowing of the cycle time. Myasthenia gravis may affect ectodermally derived smooth muscle or the autonomic neuromuscular junction or both, and not be restricted to the well-demonstrated alterations of neuromuscular junction in striated muscle of mesodermal origin. Alternatively, prolonged pupillary cycles could be attributed to dysfunction of central pathways of the pupillary light reflex."}
{"id": "PMID:228590", "title": "Enhancement of post-ultraviolet killing in Escherichia coli K-12 through the action of gyrase inhibitors: evidence for associated gyrase-recBC deoxyribonuclease function.", "content": "This work in conjunction with the results presented in an earlier report (M. A. Purdy and K. L. Yielding, Antimicrob. Agents Chemother. 10:182--184, 1976) showed the following. (i) Nalidixic acid and novobiocin could inhibit post-ultraviolet and post-X-ray survival, implicating gyrase function in deoxyribonucleic acid repair. (ii) The inhibition of post-ultraviolet survival requires the action of functional recBC deoxyribonuclease. (iii) Structural changes in the gyrase could (a) cause recBC mutants to exhibit enhancement of post-ultraviolet killing in the presence of novobiocin, (b) increase the ultraviolet sensitivity of recBC mutants, and (c) enhance the thermal lability of a recBCts mutant.", "contents": "Enhancement of post-ultraviolet killing in Escherichia coli K-12 through the action of gyrase inhibitors: evidence for associated gyrase-recBC deoxyribonuclease function. This work in conjunction with the results presented in an earlier report (M. A. Purdy and K. L. Yielding, Antimicrob. Agents Chemother. 10:182--184, 1976) showed the following. (i) Nalidixic acid and novobiocin could inhibit post-ultraviolet and post-X-ray survival, implicating gyrase function in deoxyribonucleic acid repair. (ii) The inhibition of post-ultraviolet survival requires the action of functional recBC deoxyribonuclease. (iii) Structural changes in the gyrase could (a) cause recBC mutants to exhibit enhancement of post-ultraviolet killing in the presence of novobiocin, (b) increase the ultraviolet sensitivity of recBC mutants, and (c) enhance the thermal lability of a recBCts mutant."}
{"id": "PMID:228591", "title": "Mecillinam-ampicillin synergism in experimental Enterobacteriaceae meningitis.", "content": "The in vitro activities of mecillinam, a new beta-amidinopenicillin, and ampicillin, alone and in combination, against an Escherichia coli strain and a Klebsiella pneumoniae strain were compared, and these results were correlated with their respective activities in vivo in experimental meningitis. The mecillinam-ampicillin combination was synergistic in vitro against both strains when tested by a modified checkerboard technique (bacteriostatic synergy). However when quantitative bactericidal synergy studies were made, the relative bactericidal rate of the combination was more rapid than that of either drug alone (\"bactericidal synergy\") against the Escherichia coli isolate only. In a rabbit model of Enterobacteriaceae meningitis, in vivo bactericidal activity correlated with results obtained in vitro. Both drugs were administered by continuous intravenous infusion for 8 h. Serum and cerebrospinal fluid antibiotic levels were similar to those achieved in humans. Cerebrospinal fluid bacterial concentrations (colony-forming units [CFU] per milliliter) were quantitatively titrated at 2-h intervals. Both drugs, alone or the combination, were ineffective against the K. pneumoniae strain in vivo (change in titer <1 log in 8 h). In contrast, the combination produced a markedly enhanced bactericidal effect against the E. coli strain (mean +/- standard deviation, decrease of log(10) CFU per milliliter of 3.65 +/- 1.02) compared with those of ampicillin alone (decrease of log(10) CFU per milliter of 0.07 +/- 0.8) and mecillinam alone (decrease of log(10) CFU per milliliter of 1.6 +/- 0.05) (P < 0.001). When bactericidal synergism can be demonstrated for mecillinam-ampicillin in vitro in a case of gram-negative-bacillary meningitis this combination may be useful in the therapy of the illness.", "contents": "Mecillinam-ampicillin synergism in experimental Enterobacteriaceae meningitis. The in vitro activities of mecillinam, a new beta-amidinopenicillin, and ampicillin, alone and in combination, against an Escherichia coli strain and a Klebsiella pneumoniae strain were compared, and these results were correlated with their respective activities in vivo in experimental meningitis. The mecillinam-ampicillin combination was synergistic in vitro against both strains when tested by a modified checkerboard technique (bacteriostatic synergy). However when quantitative bactericidal synergy studies were made, the relative bactericidal rate of the combination was more rapid than that of either drug alone (\"bactericidal synergy\") against the Escherichia coli isolate only. In a rabbit model of Enterobacteriaceae meningitis, in vivo bactericidal activity correlated with results obtained in vitro. Both drugs were administered by continuous intravenous infusion for 8 h. Serum and cerebrospinal fluid antibiotic levels were similar to those achieved in humans. Cerebrospinal fluid bacterial concentrations (colony-forming units [CFU] per milliliter) were quantitatively titrated at 2-h intervals. Both drugs, alone or the combination, were ineffective against the K. pneumoniae strain in vivo (change in titer <1 log in 8 h). In contrast, the combination produced a markedly enhanced bactericidal effect against the E. coli strain (mean +/- standard deviation, decrease of log(10) CFU per milliliter of 3.65 +/- 1.02) compared with those of ampicillin alone (decrease of log(10) CFU per milliter of 0.07 +/- 0.8) and mecillinam alone (decrease of log(10) CFU per milliliter of 1.6 +/- 0.05) (P < 0.001). When bactericidal synergism can be demonstrated for mecillinam-ampicillin in vitro in a case of gram-negative-bacillary meningitis this combination may be useful in the therapy of the illness."}
{"id": "PMID:228592", "title": "Aflatoxin inhibition of viral interferon induction.", "content": "The inhibitory effect of four basic aflatoxins on interferon induction by influenza virus in LLC-MK2 cell monolayers follows a structure-activity series with decreasing potency in the order aflatoxin B1 greater than G1 greater than B2 approximately G2. Of the four aflatoxins, B1 was the most deleterious to both cell growth and the viability of cells in confluent cultures. The fact that higher levels of influenza virus growth were attained in aflatoxin-treated cells than in normal cell monolayers was related to increased aflatoxin concentration in association with decreased interferon production. The ability of interferon to confer cellular resistance against viral infection, however, was not altered by aflatoxin. The inhibitory activity of aflatoxin on interferon production may be a factor contributing to impairment of host resistance to viral infections.", "contents": "Aflatoxin inhibition of viral interferon induction. The inhibitory effect of four basic aflatoxins on interferon induction by influenza virus in LLC-MK2 cell monolayers follows a structure-activity series with decreasing potency in the order aflatoxin B1 greater than G1 greater than B2 approximately G2. Of the four aflatoxins, B1 was the most deleterious to both cell growth and the viability of cells in confluent cultures. The fact that higher levels of influenza virus growth were attained in aflatoxin-treated cells than in normal cell monolayers was related to increased aflatoxin concentration in association with decreased interferon production. The ability of interferon to confer cellular resistance against viral infection, however, was not altered by aflatoxin. The inhibitory activity of aflatoxin on interferon production may be a factor contributing to impairment of host resistance to viral infections."}
{"id": "PMID:228593", "title": "Activity of semisynthetic penicillins and synergism with mecillinam against Bacteroides species.", "content": "The minimal inhibitory concentrations (MIC) of six penicillins (ampicillin, carbenicillin, ticarcillin, piperacillin, mezlocillin, and Bay k 4999) against 29 clinical isolates of Bacteriodes spp. (including Bacteroides fragilis, Bacteroides thetaiotaomicron, and Bacteroides vulgatus) were determined by an agar dilution method. Bay k 4999 was most active, followed in descending order by ampicillin, piperacillin, mezlocillin, ticarcillin, and carbenicillin. Mecillinam, a 6 beta-amidino-penicillanic acid, inhibited no strains at 50 micrograms/ml, but when compared with ampicillin, a fourfold or greater increase in MIC for ampicillin (antagonism) was noted in 3 of 29 strains, with no effect on MIC for 26 strains, whereas when combined with carbenicillin, a fourfold or greater decrease in MIC for both antibiotics (synergism) was noted in 12 strains, 4 of which had an MIC of greater than or equal to 250 micrograms/ml for carbenicillin alone. These studies demonstrate the increased activity of some newer semisynthetic penicillins and the potential synergy obtained with mecillinam and carbenicillin against Bacteroides sp.", "contents": "Activity of semisynthetic penicillins and synergism with mecillinam against Bacteroides species. The minimal inhibitory concentrations (MIC) of six penicillins (ampicillin, carbenicillin, ticarcillin, piperacillin, mezlocillin, and Bay k 4999) against 29 clinical isolates of Bacteriodes spp. (including Bacteroides fragilis, Bacteroides thetaiotaomicron, and Bacteroides vulgatus) were determined by an agar dilution method. Bay k 4999 was most active, followed in descending order by ampicillin, piperacillin, mezlocillin, ticarcillin, and carbenicillin. Mecillinam, a 6 beta-amidino-penicillanic acid, inhibited no strains at 50 micrograms/ml, but when compared with ampicillin, a fourfold or greater increase in MIC for ampicillin (antagonism) was noted in 3 of 29 strains, with no effect on MIC for 26 strains, whereas when combined with carbenicillin, a fourfold or greater decrease in MIC for both antibiotics (synergism) was noted in 12 strains, 4 of which had an MIC of greater than or equal to 250 micrograms/ml for carbenicillin alone. These studies demonstrate the increased activity of some newer semisynthetic penicillins and the potential synergy obtained with mecillinam and carbenicillin against Bacteroides sp."}
{"id": "PMID:228594", "title": "RMI 15,731 (1-[5-tetradecyloxy-2-furanyl]-ethanone), a new antirhinovirus compound.", "content": "RMI 15,731 (1-[5-tetradecyloxy-2-furanyl]-ethanone) is a new antiviral compound with activity specific for rhinoviruses. Virus synthesis in R-HeLa cells was susceptible to low concentrations (0.25 micrograms/ml) of the compound. RMI 15,731 was effective if added for 1 h before infection and removed or if added as late as 6 h postinfection. Low concentrations of the compound directly inactivated infectious rhinovirus in a time- and temperature-dependent fashion. RMI 15,731 appears to be a promising new antirhinovirus compound for clinical evaluation since it (i) blocks intracellular virus synthesis (without cellular toxicity), and (ii) directly inactivates virions. The last property may be important in limiting virus shedding from an infected host.", "contents": "RMI 15,731 (1-[5-tetradecyloxy-2-furanyl]-ethanone), a new antirhinovirus compound. RMI 15,731 (1-[5-tetradecyloxy-2-furanyl]-ethanone) is a new antiviral compound with activity specific for rhinoviruses. Virus synthesis in R-HeLa cells was susceptible to low concentrations (0.25 micrograms/ml) of the compound. RMI 15,731 was effective if added for 1 h before infection and removed or if added as late as 6 h postinfection. Low concentrations of the compound directly inactivated infectious rhinovirus in a time- and temperature-dependent fashion. RMI 15,731 appears to be a promising new antirhinovirus compound for clinical evaluation since it (i) blocks intracellular virus synthesis (without cellular toxicity), and (ii) directly inactivates virions. The last property may be important in limiting virus shedding from an infected host."}
{"id": "PMID:228595", "title": "N-alpha-Cocoyl-L-arginine ethyl ester, DL-pyroglutamic acid salt, as an inactivator of hepatitis B surface antigen.", "content": "N-alpha-Cocoyl-L-arginine ethyl ester, DL-pyroglutamic acid salt (CAE), exhibited a strong inactivating effect on hepatitis B surface antigen. Concentrations of CAE required for 50 and 100% inactivation of the antigen were 0.01 to 0.025% and 0.025 to 0.05% respectively. CAE completely inactivated hepatitis B surface antigen at the lowest concentration compared with various compounds including about 500 amino acid derivatives, sodium hypochlorite, 2,4,4'-trichloro-2'-hydroxydiphenyl ether, and some detergents. Furthermore, CAE inactivated vaccinia virus, herpes simplex virus, and influenza virus, whereas poliovirus was not inactivated at all. The results suggest that the inactivating effects of CAE are related to interaction with lipid-containing viral envelopes.", "contents": "N-alpha-Cocoyl-L-arginine ethyl ester, DL-pyroglutamic acid salt, as an inactivator of hepatitis B surface antigen. N-alpha-Cocoyl-L-arginine ethyl ester, DL-pyroglutamic acid salt (CAE), exhibited a strong inactivating effect on hepatitis B surface antigen. Concentrations of CAE required for 50 and 100% inactivation of the antigen were 0.01 to 0.025% and 0.025 to 0.05% respectively. CAE completely inactivated hepatitis B surface antigen at the lowest concentration compared with various compounds including about 500 amino acid derivatives, sodium hypochlorite, 2,4,4'-trichloro-2'-hydroxydiphenyl ether, and some detergents. Furthermore, CAE inactivated vaccinia virus, herpes simplex virus, and influenza virus, whereas poliovirus was not inactivated at all. The results suggest that the inactivating effects of CAE are related to interaction with lipid-containing viral envelopes."}
{"id": "PMID:228596", "title": "Virucidal activity of retinal.", "content": "Herpes simplex virus type 2 and simian virus 40 were rapidly inactivated by retinal at micromolar concentrations. Other fat-soluble vitamins, particularly vitamin A derivatives, were also active against herpes simplex virus type 2 and several lipid-containing bacteriophages.", "contents": "Virucidal activity of retinal. Herpes simplex virus type 2 and simian virus 40 were rapidly inactivated by retinal at micromolar concentrations. Other fat-soluble vitamins, particularly vitamin A derivatives, were also active against herpes simplex virus type 2 and several lipid-containing bacteriophages."}
{"id": "PMID:228617", "title": "Cystosarcoma phylloides. A steroid receptor and ultrastructure analysis.", "content": "Six cases of cystosarcoma phylloides were evaluated by ultrastructure and steroid receptor analysis. Electron microscopy of the lesions supported previous reports of a heterogeneous tumor consisting of pleomorphic mesenchyme and normal or proliferative epithelium. In each case estrogen and progesterone receptor analysis indicated the presence of a nonsaturable estrogen and progesterone 4S binding protein rather than a specific steroid receptor as suggested by previous studies.", "contents": "Cystosarcoma phylloides. A steroid receptor and ultrastructure analysis. Six cases of cystosarcoma phylloides were evaluated by ultrastructure and steroid receptor analysis. Electron microscopy of the lesions supported previous reports of a heterogeneous tumor consisting of pleomorphic mesenchyme and normal or proliferative epithelium. In each case estrogen and progesterone receptor analysis indicated the presence of a nonsaturable estrogen and progesterone 4S binding protein rather than a specific steroid receptor as suggested by previous studies."}
{"id": "PMID:228618", "title": "The pathologic assessment of primary hyperparathyroidism and its impact on therapy. A prospective evaluation of 50 cases with oil-red-O stain.", "content": "Normal and abnormal parathyroid glands removed surgically from 50 consecutive patients with primary hyperparathyroidism were studied by means of hematoxylin and eosin and oil-red-O stains. This was done to establish the incidence of the different pathological entities in our patient material, and to evaluate the role of the oil-red-O stain in the diagnostic histopathological process. The oil-red-O stain distinctly separates abnormally hyperfunctioning from normal or suppressed parathyroid tissue. Therefore, it is a valuable tool in the pathologic evaluation of patients with hyperparathyroidism. Chief cell adenomas were the most frequent lesions (88%), while diffuse hyperplasia was seen less commonly (10%) and carcinoma infrequently (2%). These findings justify a surgically conservative approach as the most desirable in managing patients with primary hyperparathyroidism.", "contents": "The pathologic assessment of primary hyperparathyroidism and its impact on therapy. A prospective evaluation of 50 cases with oil-red-O stain. Normal and abnormal parathyroid glands removed surgically from 50 consecutive patients with primary hyperparathyroidism were studied by means of hematoxylin and eosin and oil-red-O stains. This was done to establish the incidence of the different pathological entities in our patient material, and to evaluate the role of the oil-red-O stain in the diagnostic histopathological process. The oil-red-O stain distinctly separates abnormally hyperfunctioning from normal or suppressed parathyroid tissue. Therefore, it is a valuable tool in the pathologic evaluation of patients with hyperparathyroidism. Chief cell adenomas were the most frequent lesions (88%), while diffuse hyperplasia was seen less commonly (10%) and carcinoma infrequently (2%). These findings justify a surgically conservative approach as the most desirable in managing patients with primary hyperparathyroidism."}
{"id": "PMID:228619", "title": "[Preliminary note on the circulation of some human respiratory viruses by wild birds].", "content": "With a view to detecting infections and carriage of human respiratory viruses in wild birds, 349 serum samples collected from 21 bird species -- sedentary ones and birds with large or limited migration areas -- were investigated. The following antigens were used: influenza virus A/Hong Kong 1/68 (H3N2)), A2 England 42/73 (H3N2), A2 Victoria 3/75 (H3N2), A/New Jersey 8/76 (HswN1), B/Hong Kong 5/72; parainfluenza virus type I Sendai and type II, coronavirus OC/43. An elevated incidence of antibodies to A2 Victoria 3/75 (H3N2) and parainfluenza type I virus was detected in herons (Ardea cinerea, Nyctycorax myctycorax). The high incidence of antibodies to B/Hong Kong 5/72 (30.7% of the samples exhibited significant titers) found in the crow (Corvus corone sardonius) is ascribed to the fact that this bird is carnivorus, feeding on corpses of mammals.", "contents": "[Preliminary note on the circulation of some human respiratory viruses by wild birds]. With a view to detecting infections and carriage of human respiratory viruses in wild birds, 349 serum samples collected from 21 bird species -- sedentary ones and birds with large or limited migration areas -- were investigated. The following antigens were used: influenza virus A/Hong Kong 1/68 (H3N2)), A2 England 42/73 (H3N2), A2 Victoria 3/75 (H3N2), A/New Jersey 8/76 (HswN1), B/Hong Kong 5/72; parainfluenza virus type I Sendai and type II, coronavirus OC/43. An elevated incidence of antibodies to A2 Victoria 3/75 (H3N2) and parainfluenza type I virus was detected in herons (Ardea cinerea, Nyctycorax myctycorax). The high incidence of antibodies to B/Hong Kong 5/72 (30.7% of the samples exhibited significant titers) found in the crow (Corvus corone sardonius) is ascribed to the fact that this bird is carnivorus, feeding on corpses of mammals."}
{"id": "PMID:228620", "title": "Effect of guanethidine on collagen biosynthesis in blood vessels of hypertensive rats.", "content": "The effect of guanethidine on collagen biosynthesis in the aorta and mesenteric artery was investigated in desoxycorticosterone acetate (DOCA)-salt hypertensive rats. Prolyl hydroxylase activity (EC 1.14.11.2; proline, 2-oxoglutarate dioxygenase) and 14C-proline incorporation into collagen, two markers of collagen biosynthesis, were significantly increased in blood vessels of hypertensive rats compared with those of controls. When guanethidine (5 mg/kg, i.p.) was given daily to the hypertensive rats for 4 weeks, the blood pressure was decreased to 150 +/- 7 mm Hg, whereas the blood pressure of the untreated hypertensive rats was 218 +/- 10 mm Hg. Prolyl hydroxylase activity in the aorta and mesenteric artery and 14C-proline incorporation into aortic collagen were significantly reduced concomitant with the decrease in blood pressure. These results suggest that the decrease in vascular collagen biosynthesis in hypertensive rats treated with guanethidine is related to the lowering of their blood pressure.", "contents": "Effect of guanethidine on collagen biosynthesis in blood vessels of hypertensive rats. The effect of guanethidine on collagen biosynthesis in the aorta and mesenteric artery was investigated in desoxycorticosterone acetate (DOCA)-salt hypertensive rats. Prolyl hydroxylase activity (EC 1.14.11.2; proline, 2-oxoglutarate dioxygenase) and 14C-proline incorporation into collagen, two markers of collagen biosynthesis, were significantly increased in blood vessels of hypertensive rats compared with those of controls. When guanethidine (5 mg/kg, i.p.) was given daily to the hypertensive rats for 4 weeks, the blood pressure was decreased to 150 +/- 7 mm Hg, whereas the blood pressure of the untreated hypertensive rats was 218 +/- 10 mm Hg. Prolyl hydroxylase activity in the aorta and mesenteric artery and 14C-proline incorporation into aortic collagen were significantly reduced concomitant with the decrease in blood pressure. These results suggest that the decrease in vascular collagen biosynthesis in hypertensive rats treated with guanethidine is related to the lowering of their blood pressure."}
{"id": "PMID:228623", "title": "[Activity of delta-aminolevulinic synthetase, cytochrome oxidase and levels of the mixed function oxidase system during experimental protein malnutrition. Response to re-alimentation].", "content": "Activities of delta amino levulinic synthetase (DALS), cytochrome oxidase (E. C. 1.9.3.1.), NADH cytochrome b5 reductase (NADH red.), NADPH cytochrome P450 reductase (NADPH red.), contents of cytochrome P450 (cyt. P450) and cytochrome b5 (cyt. b5), and levels of hemoglobin and hematocrit were studied in three groups of rats: a) malnourished, b) during recovery from malnutrition, and c) controls. During severe protein malnutrition blood levels of hemoglobin and hematocrit were found to be decreased as well as DALS's activity in homogenized bone marrow and liver. The activity of NADH red, and contents of cyt. P.450 and cyt. b5 in hepatic microsomes were also found significantly depressed. The microsomal activity of NADPH red. as well as mitochondrial cytochrome oxidase did not present significant changes, since values obtained in malnourished rats were similar to those found for the control group. While recovering from malnutrition, when rats were fed a casein based diet (10 NDpCalo/o) supplemented with Fe and Cu, the hepatic enzymatic activities, the cytochrome contents of P450 and b5, and hematocrit experienced a spectacular increase, reaching towards the end of the refeeding period values which could be compared to those found in the control group. Nevertheless, DALS' activity in homogenized bone marrow and hemoglobin levels remained low. Results are discussed in relation to depressed activities and contents of enzymes, coenzymes, metabolites and subtrates involved in the hemoglobin synthesis in the rat bone marrow, during recovery from malnutrition.", "contents": "[Activity of delta-aminolevulinic synthetase, cytochrome oxidase and levels of the mixed function oxidase system during experimental protein malnutrition. Response to re-alimentation]. Activities of delta amino levulinic synthetase (DALS), cytochrome oxidase (E. C. 1.9.3.1.), NADH cytochrome b5 reductase (NADH red.), NADPH cytochrome P450 reductase (NADPH red.), contents of cytochrome P450 (cyt. P450) and cytochrome b5 (cyt. b5), and levels of hemoglobin and hematocrit were studied in three groups of rats: a) malnourished, b) during recovery from malnutrition, and c) controls. During severe protein malnutrition blood levels of hemoglobin and hematocrit were found to be decreased as well as DALS's activity in homogenized bone marrow and liver. The activity of NADH red, and contents of cyt. P.450 and cyt. b5 in hepatic microsomes were also found significantly depressed. The microsomal activity of NADPH red. as well as mitochondrial cytochrome oxidase did not present significant changes, since values obtained in malnourished rats were similar to those found for the control group. While recovering from malnutrition, when rats were fed a casein based diet (10 NDpCalo/o) supplemented with Fe and Cu, the hepatic enzymatic activities, the cytochrome contents of P450 and b5, and hematocrit experienced a spectacular increase, reaching towards the end of the refeeding period values which could be compared to those found in the control group. Nevertheless, DALS' activity in homogenized bone marrow and hemoglobin levels remained low. Results are discussed in relation to depressed activities and contents of enzymes, coenzymes, metabolites and subtrates involved in the hemoglobin synthesis in the rat bone marrow, during recovery from malnutrition."}
{"id": "PMID:228625", "title": "[Enzyme arrangement of various tissues in swine. 1. Studies of the effect of 32 hours of fasting, administration of actinomycin D, and fasting in combination with administration of actinomycin D on crude protein level, activities of GOT, GTP, fructose-1,6-diphoaphatase as well as ATPase of liver, kidneys and semitendinous muscle in newborn piglets].", "content": "The effects of sufficient milk intake as well as of 32 hours of fasting after birth, administration of actinomycin D (intraperitoneal application of 1 mg/kg five weight), and fasting in combination with actinomycin D on the development of body and liver weights, crude protein levels in homogenate and supernatant of liver, kidneys, and M. semitendinosus as well as on the activities of certain tissue enzymes were analysed with four groups of piglets (n = 4). Fasting, administration of actinomycin, and fasting in combination with actinomycin D resulted in rapid reduction in body and liver weights, while the crude protein levels in those tissues were not affected with significance. GOT and fructose-1,6-diphosphatase activities in supernatant from liver tended to decline under fasting conditions. The ATPase activity in the homogenate of the above tissues did not change in response to differentiated treatment.", "contents": "[Enzyme arrangement of various tissues in swine. 1. Studies of the effect of 32 hours of fasting, administration of actinomycin D, and fasting in combination with administration of actinomycin D on crude protein level, activities of GOT, GTP, fructose-1,6-diphoaphatase as well as ATPase of liver, kidneys and semitendinous muscle in newborn piglets]. The effects of sufficient milk intake as well as of 32 hours of fasting after birth, administration of actinomycin D (intraperitoneal application of 1 mg/kg five weight), and fasting in combination with actinomycin D on the development of body and liver weights, crude protein levels in homogenate and supernatant of liver, kidneys, and M. semitendinosus as well as on the activities of certain tissue enzymes were analysed with four groups of piglets (n = 4). Fasting, administration of actinomycin, and fasting in combination with actinomycin D resulted in rapid reduction in body and liver weights, while the crude protein levels in those tissues were not affected with significance. GOT and fructose-1,6-diphosphatase activities in supernatant from liver tended to decline under fasting conditions. The ATPase activity in the homogenate of the above tissues did not change in response to differentiated treatment."}
{"id": "PMID:228626", "title": "[Enzyme arrangement of various tissues in swine. 2. Studies of postpartum development of crude protein levels as well as activities of various enzymes (GOT, GPT, serine dehydratase, xanthine oxidase, fructose-1,6-diphosphatase) in liver, kidneys and muscle of piglets].", "content": "Twenty-eight piglets from three litters were analysed for postnatal development (0 to 6 days of age) of the crude protein levels and activities of various enzymes (GOT, GPT, serine dehydratase, xanthinoxidase, fructose-1,6-diphosphatase) in the supernatant of liver, kidneys, and muscles. Both the weight and crude protein levels of the liver increased after birth, which improved the capability of metabolic regulation. GOT and fructose 1,6-diphosphatase activities in the liver tissue increased over the first days after birth. Serine dehydratase activity was not detectable with regularity. GPT activity in the tissues concerned was low by comparison to GOT and underwent little postnatal change. The activity of xanthinoxidase in the liver tissue tended to go up after birth. ACTH (3 IU/kg live weight) was administered to piglets aged five days and did not increase the activity of GOT and fructose-1,6-diphosphatase in the liver after five hours.", "contents": "[Enzyme arrangement of various tissues in swine. 2. Studies of postpartum development of crude protein levels as well as activities of various enzymes (GOT, GPT, serine dehydratase, xanthine oxidase, fructose-1,6-diphosphatase) in liver, kidneys and muscle of piglets]. Twenty-eight piglets from three litters were analysed for postnatal development (0 to 6 days of age) of the crude protein levels and activities of various enzymes (GOT, GPT, serine dehydratase, xanthinoxidase, fructose-1,6-diphosphatase) in the supernatant of liver, kidneys, and muscles. Both the weight and crude protein levels of the liver increased after birth, which improved the capability of metabolic regulation. GOT and fructose 1,6-diphosphatase activities in the liver tissue increased over the first days after birth. Serine dehydratase activity was not detectable with regularity. GPT activity in the tissues concerned was low by comparison to GOT and underwent little postnatal change. The activity of xanthinoxidase in the liver tissue tended to go up after birth. ACTH (3 IU/kg live weight) was administered to piglets aged five days and did not increase the activity of GOT and fructose-1,6-diphosphatase in the liver after five hours."}
{"id": "PMID:228627", "title": "[Enzyme arrangement of various tissues in swine. 3. Studies of pre- and postnatal activities of various enzymes (ATPase, GOT, GPT, leucine aminopeptidase, acid and alkaline phosphatases, aldose reductase, glucuronate reductase, sorbitol dehydrogenase) in various tissues].", "content": "The crude protein levels as well as the activities of various enzymes were studied in certain tissues of fetuses (80th through 114th days of development), piglets of different age groups, and pigs for slaughter. In most of the tissues tested the postnatal activities of Na-K-ATPase were beyond those recorded from fetuses. The highest GOT activities were recorded from the liver, myocardium, and kidneys. Activities were found to rise sizeably in some tissues after birth. The activity of GPT, too, exhibited age-dependent variations. The activity of leucine-aminopeptidase increased strongly after birth in liver and kidneys. Acid phosphatase activity was less markedly influenced by development phases. Those enzymes which are involved in the formation of fructose and glucose (aldolreductase, glucuronate-reductase, and sorbite-dehydrogenase) had their highest activities, all age-dependent, in liver and kidneys.", "contents": "[Enzyme arrangement of various tissues in swine. 3. Studies of pre- and postnatal activities of various enzymes (ATPase, GOT, GPT, leucine aminopeptidase, acid and alkaline phosphatases, aldose reductase, glucuronate reductase, sorbitol dehydrogenase) in various tissues]. The crude protein levels as well as the activities of various enzymes were studied in certain tissues of fetuses (80th through 114th days of development), piglets of different age groups, and pigs for slaughter. In most of the tissues tested the postnatal activities of Na-K-ATPase were beyond those recorded from fetuses. The highest GOT activities were recorded from the liver, myocardium, and kidneys. Activities were found to rise sizeably in some tissues after birth. The activity of GPT, too, exhibited age-dependent variations. The activity of leucine-aminopeptidase increased strongly after birth in liver and kidneys. Acid phosphatase activity was less markedly influenced by development phases. Those enzymes which are involved in the formation of fructose and glucose (aldolreductase, glucuronate-reductase, and sorbite-dehydrogenase) had their highest activities, all age-dependent, in liver and kidneys."}
{"id": "PMID:228628", "title": "[Histopathological pattern of adenovirus infection in the calf].", "content": "Pneumo-enteritis is the clinical manifestation of adenovirus infection in calf. Proliferative alveolitis, endobronchitis, and peribronchitis with intranuclear inclusions in the epithelial cells, histiocytes, and macrophages were histologically recorded. Proliferative changes with minor pleomorphism of cells were recorded from lymph nodes and lymph follicles of spleen and intestines. The epithelial cells of the renal tubules and liver exhibited degenerative changes, while the endothelium of the capillaries was activated. Five Serotype-1 adenoviruses were isolated from the lung, liver, and kidneys of the foetuses. IE were recordable from the epithelial cells of kidneys and lung. Other calves were examined following natural infection with adenovirus and virus of the mucosa disease. Dystrophic and necrotic changes were recorded from their digestive organs, lymphocytolysis from spleen and lymph nodes (a characteristic change related to mucosa disease), and nephrosis with adenovirus inclusions from the epithelial cells of the renal tubules.", "contents": "[Histopathological pattern of adenovirus infection in the calf]. Pneumo-enteritis is the clinical manifestation of adenovirus infection in calf. Proliferative alveolitis, endobronchitis, and peribronchitis with intranuclear inclusions in the epithelial cells, histiocytes, and macrophages were histologically recorded. Proliferative changes with minor pleomorphism of cells were recorded from lymph nodes and lymph follicles of spleen and intestines. The epithelial cells of the renal tubules and liver exhibited degenerative changes, while the endothelium of the capillaries was activated. Five Serotype-1 adenoviruses were isolated from the lung, liver, and kidneys of the foetuses. IE were recordable from the epithelial cells of kidneys and lung. Other calves were examined following natural infection with adenovirus and virus of the mucosa disease. Dystrophic and necrotic changes were recorded from their digestive organs, lymphocytolysis from spleen and lymph nodes (a characteristic change related to mucosa disease), and nephrosis with adenovirus inclusions from the epithelial cells of the renal tubules."}
{"id": "PMID:228629", "title": "[Studies of necrotizing enteritis of suckling piglets (Cl. perfringens typc C enterotoxemia) in industrialized sow breeding units. 3. Experimental reproduction of the disease].", "content": "Experimental reproduction of necrotising enteritis of sucking pigs was successfully achieved by using both Clostridium perfringens Type C strains, which had been isolated from sucking pigs with necrotising enteritis, and Type C strain 3628 of A.T.C.C. (sub-type C1). The lethal dose for sucking pigs was between 20 X 10(6) and 12 X 10(7) pathogens per animal. The disease could not even be induced by repeated application of no-bacterial toxin of Cl. perfringens Type C nor by administration of Cl. perfringens Type A strains which had been cultured from broilers with necrotising enteritis. Necrotising enteritis was found to develop in two phases in sucking pigs. First, the pathogen will deposit to the villous epithelium and then penetrate the superficial strata of the mocous membrane. In the second phase, the villous structure will be destroyed by the lethal, haemolysing, and necrotising toxins of Cl. perfringens. The role played by individual toxin fractions is discussed together with the importance of humoral and localised infection defence. Sucking pigs may be sufficiently protected against infection based on single or ten-fold lethal infectious dosage by two vaccinations of the mother animal, five and three weeks prior to parturition, using \"Enterotoxaemia Vaccine Dessau bivalent\". Infection then would not occur unless a hundredfold lethal dose was applied. Characteristics include diarrhoea, apathy, exhaustion, and death.", "contents": "[Studies of necrotizing enteritis of suckling piglets (Cl. perfringens typc C enterotoxemia) in industrialized sow breeding units. 3. Experimental reproduction of the disease]. Experimental reproduction of necrotising enteritis of sucking pigs was successfully achieved by using both Clostridium perfringens Type C strains, which had been isolated from sucking pigs with necrotising enteritis, and Type C strain 3628 of A.T.C.C. (sub-type C1). The lethal dose for sucking pigs was between 20 X 10(6) and 12 X 10(7) pathogens per animal. The disease could not even be induced by repeated application of no-bacterial toxin of Cl. perfringens Type C nor by administration of Cl. perfringens Type A strains which had been cultured from broilers with necrotising enteritis. Necrotising enteritis was found to develop in two phases in sucking pigs. First, the pathogen will deposit to the villous epithelium and then penetrate the superficial strata of the mocous membrane. In the second phase, the villous structure will be destroyed by the lethal, haemolysing, and necrotising toxins of Cl. perfringens. The role played by individual toxin fractions is discussed together with the importance of humoral and localised infection defence. Sucking pigs may be sufficiently protected against infection based on single or ten-fold lethal infectious dosage by two vaccinations of the mother animal, five and three weeks prior to parturition, using \"Enterotoxaemia Vaccine Dessau bivalent\". Infection then would not occur unless a hundredfold lethal dose was applied. Characteristics include diarrhoea, apathy, exhaustion, and death."}
{"id": "PMID:228630", "title": "Human adenohypophyseal quantitative histochemical cell classification. II. Evaluation of the effects of two fixatives and postmortem intervals.", "content": "Quantitative cell counts on specific pituitary areas were done on differentially stained adenohypophyseal sections obtained at autopsy (four to 22 hours postmortem). We used specific criteria formulated from studies by previous authors to identify functional classes of secretory cells. We compared the effects of two fixatives, calcium acetate-buffered formaldehyde solution (CAF) and formol sublimate (FS), on morphologic identification. Calcium acetate-buffered formaldehyde solution is superior in identifying gonadotrophs and prolactin cells morphologically. Formol sublimate is superior in identifying the other cell types morphologically. Approximately 10% to 15% more cells could be classified by fixing with FS rather than CAF. The effect of postmortem autolysis was minimal. The only statistically significant (P less than .025) effect was the presence of a higher percentage of disrupted unclassifiable cells in CAF-fixed basophil areas at 12 to 24 hours than was present at 0 to 12 hours.", "contents": "Human adenohypophyseal quantitative histochemical cell classification. II. Evaluation of the effects of two fixatives and postmortem intervals. Quantitative cell counts on specific pituitary areas were done on differentially stained adenohypophyseal sections obtained at autopsy (four to 22 hours postmortem). We used specific criteria formulated from studies by previous authors to identify functional classes of secretory cells. We compared the effects of two fixatives, calcium acetate-buffered formaldehyde solution (CAF) and formol sublimate (FS), on morphologic identification. Calcium acetate-buffered formaldehyde solution is superior in identifying gonadotrophs and prolactin cells morphologically. Formol sublimate is superior in identifying the other cell types morphologically. Approximately 10% to 15% more cells could be classified by fixing with FS rather than CAF. The effect of postmortem autolysis was minimal. The only statistically significant (P less than .025) effect was the presence of a higher percentage of disrupted unclassifiable cells in CAF-fixed basophil areas at 12 to 24 hours than was present at 0 to 12 hours."}
{"id": "PMID:228632", "title": "Ultrastructure of psammoma bodies of meningioma in tissue culture.", "content": "An 8-day-old tissue culture of a human meningioma was studied by electron microscopy. Psammoma bodies were detected in all stages of evolution, affording a unique opportunity for observing the genesis of these structures. Matrix vesicles appeared instrumental in the calcification of a granular extracellular material. Although matrix vesicles are described in both physiologic and pathologic calcification, they have not been previously reported in the very few ultrastructural studies of psammoma bodies in meningiomas.", "contents": "Ultrastructure of psammoma bodies of meningioma in tissue culture. An 8-day-old tissue culture of a human meningioma was studied by electron microscopy. Psammoma bodies were detected in all stages of evolution, affording a unique opportunity for observing the genesis of these structures. Matrix vesicles appeared instrumental in the calcification of a granular extracellular material. Although matrix vesicles are described in both physiologic and pathologic calcification, they have not been previously reported in the very few ultrastructural studies of psammoma bodies in meningiomas."}
{"id": "PMID:228633", "title": "Malakoplakia of the brain. A report of two cases occurring in childhood.", "content": "Malakoplakia was found in the brain biopsy specimens of two children with meningoencephalitis probably due to herpes simplex. Histologically, there was extensive parenchymal destruction and cellular infiltration. Numerous von Hansemann histiocytes and typical Michaelis-Gutmann bodies were present. Ultrastructurally these bodies had a dense central core and concentric alternating rings. Large intracytoplasmic phagolysosomes were present. Malakoplakia most frequently involves the urinary tract of adults. Only a few children with malakoplakia have been described. There are two previous reports of cerebral malakoplakia associated with neonatal herpes simplex. The pathogenesis is obscure. Several reports suggest an altered histiocytic response to a bacterial agent as the pathogenetic mechanism. Our findings raise the possibility of an etiologic role of a virus, such as herpes simplex.", "contents": "Malakoplakia of the brain. A report of two cases occurring in childhood. Malakoplakia was found in the brain biopsy specimens of two children with meningoencephalitis probably due to herpes simplex. Histologically, there was extensive parenchymal destruction and cellular infiltration. Numerous von Hansemann histiocytes and typical Michaelis-Gutmann bodies were present. Ultrastructurally these bodies had a dense central core and concentric alternating rings. Large intracytoplasmic phagolysosomes were present. Malakoplakia most frequently involves the urinary tract of adults. Only a few children with malakoplakia have been described. There are two previous reports of cerebral malakoplakia associated with neonatal herpes simplex. The pathogenesis is obscure. Several reports suggest an altered histiocytic response to a bacterial agent as the pathogenetic mechanism. Our findings raise the possibility of an etiologic role of a virus, such as herpes simplex."}
{"id": "PMID:228635", "title": "Induction of virus specific and H-2 restricted cytotoxic T cells by UV inactivated murine cytomegalovirus.", "content": "Infection of C3H mice with live or UV-inactivated murine cytomegalovirus (MCMV) was able to generate population(s) of lymphocytes in the spleen (CTL) which could exert a lytic effect against L cells infected with MCMV but not against uninfected or those infected with HSV-1. The effector cells proved to be theta-bearing T cells and the lysis of target cells was H-2 restricted. Data presented show that early viral protein synthesis but not viral DNA synthesis was necessary for the appearance of relevant antigenic determinant(s) on target cells. The results of co-capping experiments suggest that H-2 molecules may have close association with MCMV induced product(s) as also with murine leukemia virus glycoprotein (gp70) which is carried by normal L cells. Despite this observation, anti-H-2 serum effectively blocked the cytolysis whereas anti-gp70 and anti-MCMV sera failed. Anti-MCMV serum was effective in blocking cytolysis, only if the L cells were infected for 24 hours and then used as targets. MCMV infected L cells which were coated externally with inactivated Sendai virus could be effectively recognised by MCMV as also by sendai specific CTL. That the cytotoxicity exerted on such targets was of specific nature was revealed by the results of competitive blocking experiments with unlabelled targets.", "contents": "Induction of virus specific and H-2 restricted cytotoxic T cells by UV inactivated murine cytomegalovirus. Infection of C3H mice with live or UV-inactivated murine cytomegalovirus (MCMV) was able to generate population(s) of lymphocytes in the spleen (CTL) which could exert a lytic effect against L cells infected with MCMV but not against uninfected or those infected with HSV-1. The effector cells proved to be theta-bearing T cells and the lysis of target cells was H-2 restricted. Data presented show that early viral protein synthesis but not viral DNA synthesis was necessary for the appearance of relevant antigenic determinant(s) on target cells. The results of co-capping experiments suggest that H-2 molecules may have close association with MCMV induced product(s) as also with murine leukemia virus glycoprotein (gp70) which is carried by normal L cells. Despite this observation, anti-H-2 serum effectively blocked the cytolysis whereas anti-gp70 and anti-MCMV sera failed. Anti-MCMV serum was effective in blocking cytolysis, only if the L cells were infected for 24 hours and then used as targets. MCMV infected L cells which were coated externally with inactivated Sendai virus could be effectively recognised by MCMV as also by sendai specific CTL. That the cytotoxicity exerted on such targets was of specific nature was revealed by the results of competitive blocking experiments with unlabelled targets."}
{"id": "PMID:228636", "title": "Studies on avian infectious bronchitis virus (IBV). III. Interferon induction by and sensitivity to interferon of IBV.", "content": "The induction of interferon by avian infectious bronchitis virus (IBV) and the sensitivity of IBV to interferon were studied. The results of experiments with ten IBV strains are summarized as follows. 1. All the IBV strains tested induced interferon in chick embryo (CE) cells, chicken kidney (CK) cells and embryonated eggs. The Iowa-609 strain induced about 1000 units of interferon in CE cells while the Beaudette-42 strain induced about 200 units of interferon in embryonated eggs; the interferon titers induced by other strains usually ranged from 5 to 60 units. No IBV strain induced interferon in HeLa or BHK-21 cells. 2. IBV particles inactivated by ultraviolet irradiation or by heating lost their ability to induce interferon. 3. The properties of the interferon produced in the present study are similar to those of other interferons produced in chicken cells. 4. HeLa or BHK-21 cells did not acquire resistance to virus infection, after incubation with interferon produced in CE cells. On the other hand, CK cells acquired the same degree of resistance to virus infection as CE cells after incubation with interferon produced in CE cells. 5. All the IBV strains tested were sensitive to interferon in CK cells. The sensitivities of Massachusetts-41 and Holte strains to interferon were similar to that of vesicular stomatitis virus.", "contents": "Studies on avian infectious bronchitis virus (IBV). III. Interferon induction by and sensitivity to interferon of IBV. The induction of interferon by avian infectious bronchitis virus (IBV) and the sensitivity of IBV to interferon were studied. The results of experiments with ten IBV strains are summarized as follows. 1. All the IBV strains tested induced interferon in chick embryo (CE) cells, chicken kidney (CK) cells and embryonated eggs. The Iowa-609 strain induced about 1000 units of interferon in CE cells while the Beaudette-42 strain induced about 200 units of interferon in embryonated eggs; the interferon titers induced by other strains usually ranged from 5 to 60 units. No IBV strain induced interferon in HeLa or BHK-21 cells. 2. IBV particles inactivated by ultraviolet irradiation or by heating lost their ability to induce interferon. 3. The properties of the interferon produced in the present study are similar to those of other interferons produced in chicken cells. 4. HeLa or BHK-21 cells did not acquire resistance to virus infection, after incubation with interferon produced in CE cells. On the other hand, CK cells acquired the same degree of resistance to virus infection as CE cells after incubation with interferon produced in CE cells. 5. All the IBV strains tested were sensitive to interferon in CK cells. The sensitivities of Massachusetts-41 and Holte strains to interferon were similar to that of vesicular stomatitis virus."}
{"id": "PMID:228634", "title": "[Na K ATPase changes in the erythrocyte membrane in subjects treated with inosine].", "content": "The effect of inosine on red cell membrane Na+K+ATPase in lead poisoning was studied in 13 subjects. In addition to enzyme damage, an appreciable increase in enzyme level was noted after 100 mg inosine i.m. for 20 days. It is felt that this form of management is useful in lead poisoning as a means of treating and preventing anaemia.", "contents": "[Na K ATPase changes in the erythrocyte membrane in subjects treated with inosine]. The effect of inosine on red cell membrane Na+K+ATPase in lead poisoning was studied in 13 subjects. In addition to enzyme damage, an appreciable increase in enzyme level was noted after 100 mg inosine i.m. for 20 days. It is felt that this form of management is useful in lead poisoning as a means of treating and preventing anaemia."}
{"id": "PMID:228637", "title": "Biochemical studies with infectious bursal disease virus: comparison of some of its properties with infectious pancreatic necrosis virus.", "content": "Infectious bursal disease (IBD) virus was purified from the bursae of infected chickens. Two morphologically indistinguishable populations of virus particles were separated in sucrose gradients and possessed sedimentation coefficients of 295S and 460S. Both populations contained RNA and had identical polypeptide compositions. IBD virus banded at a density of 1.31 g/ml in CsCl and at 1.24 g/ml in sodium potassium tartrate. IBD virus contained two RNA segments with mol. wts. of 2.4X10(6) and 2.2X10(6) as estimated by polyacrylamide-agarose gel electrophoresis, but sedimented in sucrose gradients at 15S. Virus RNA was resistant to 0.1 micrograms/ml ribonuclease treatment under conditions in which ribosomal RNA was completely hydrolysed, but was sensitive to 1.0 and 10 micrograms/ml treatments. These results suggest that the RNA consists of either double-stranded or highly ordered single-stranded molecules. IBD virus contained seven polypeptides with mol. wts. in the range 97,000 to 24,000. Two polypeptides were absent in empty particles of IBD virus. IBD and infectious pancreatic necrosis (IPN) viruses were morphologically indistinguishable. IPN virus possessed a sedimentation coefficient of 440S and banded at a density of 1.32 g/ml in CsCl. In addition the electrophoretic mobilities of IBD and IPN virus RNAs were almost identical. Polyacrylamide slab gel electrophoresis showed that while the number and size of the polypeptides were different for each virus there were similarities in the overall pattern.", "contents": "Biochemical studies with infectious bursal disease virus: comparison of some of its properties with infectious pancreatic necrosis virus. Infectious bursal disease (IBD) virus was purified from the bursae of infected chickens. Two morphologically indistinguishable populations of virus particles were separated in sucrose gradients and possessed sedimentation coefficients of 295S and 460S. Both populations contained RNA and had identical polypeptide compositions. IBD virus banded at a density of 1.31 g/ml in CsCl and at 1.24 g/ml in sodium potassium tartrate. IBD virus contained two RNA segments with mol. wts. of 2.4X10(6) and 2.2X10(6) as estimated by polyacrylamide-agarose gel electrophoresis, but sedimented in sucrose gradients at 15S. Virus RNA was resistant to 0.1 micrograms/ml ribonuclease treatment under conditions in which ribosomal RNA was completely hydrolysed, but was sensitive to 1.0 and 10 micrograms/ml treatments. These results suggest that the RNA consists of either double-stranded or highly ordered single-stranded molecules. IBD virus contained seven polypeptides with mol. wts. in the range 97,000 to 24,000. Two polypeptides were absent in empty particles of IBD virus. IBD and infectious pancreatic necrosis (IPN) viruses were morphologically indistinguishable. IPN virus possessed a sedimentation coefficient of 440S and banded at a density of 1.32 g/ml in CsCl. In addition the electrophoretic mobilities of IBD and IPN virus RNAs were almost identical. Polyacrylamide slab gel electrophoresis showed that while the number and size of the polypeptides were different for each virus there were similarities in the overall pattern."}
{"id": "PMID:228638", "title": "Characterization of the infection of equine fibroblasts by equine infectious anemia virus.", "content": "Equine dermal fibroblasts persistently infected with equine infectious anemia virus (EIAV) show no alterations in cell morphology or growth kinetics when compared to uninfected cells. The percentage of cells immunofluorescent positive for viral proteins fluctuated, depending upon the stage of the cell cycle, while production of extracellular virus was uniform throughout the cell cycle, increasing only as the cell number increased. This was shown in log versus stationary phase cultures as well as in cultures synchronized by sterum starvation. The establishment of productive infection did not require host cell DNA synthesis. Normal levels of progeny virus were produced in cultures pretreated with mitomycin C and placed in serum-containing medium. Serum-starved cultures, however, did not support EIAV replication as well as other cultures, presumably because synthesis of provirus was inhibited.", "contents": "Characterization of the infection of equine fibroblasts by equine infectious anemia virus. Equine dermal fibroblasts persistently infected with equine infectious anemia virus (EIAV) show no alterations in cell morphology or growth kinetics when compared to uninfected cells. The percentage of cells immunofluorescent positive for viral proteins fluctuated, depending upon the stage of the cell cycle, while production of extracellular virus was uniform throughout the cell cycle, increasing only as the cell number increased. This was shown in log versus stationary phase cultures as well as in cultures synchronized by sterum starvation. The establishment of productive infection did not require host cell DNA synthesis. Normal levels of progeny virus were produced in cultures pretreated with mitomycin C and placed in serum-containing medium. Serum-starved cultures, however, did not support EIAV replication as well as other cultures, presumably because synthesis of provirus was inhibited."}
{"id": "PMID:228639", "title": "Enterovirus 71 isolated from cases of epidemic poliomyelitis-like disease in Bulgaria.", "content": "Virological and serological studies of an epidemic disease in Bulgaria, 1975, were carried out. Epidemiologically, clinically and pathomorphologically, the disease simulated almost all known forms of poliomyelitis, acute stem encephalitis, encephalomyocarditis and aseptic meningitis. The studies completely rules out the participation of polioviruses and provided comprehensive evidence for the etiological role of a peculiar enterovirus subsequently identified as enterovirus (EV) type 71 known in the literature since 1974. Altogether, in 1975 and 1976 from 65 cases of poliomyelitis-like disease (PLD) 92 strains of EV71 were isolated, including 37 strains from the brain and medulla, 1 from the cerebrospinal fluid, 10 from mesenterial lymph nodes and tonsils and 44 from faeces. In addition, in 282 convalescent cases of the disease, diagnostic seroconversion or high titers of antibody to this virus were demonstrated. The most successful virus isolation was achieved by inoculation of green monkey kidney cell cultures and newborn white mice. Bulgarian strains of enterovirus 71 regularly caused paralysis in monkeys and morphological poliomyelitis-like lesions in their CNS, and paralysis and myositis with Zenker necrosis in newborn white mice, cotton rats, Syrian hamsters, and 3-week-old cotton rats. The diseased rodents had much more virus in their mucles than in brains.", "contents": "Enterovirus 71 isolated from cases of epidemic poliomyelitis-like disease in Bulgaria. Virological and serological studies of an epidemic disease in Bulgaria, 1975, were carried out. Epidemiologically, clinically and pathomorphologically, the disease simulated almost all known forms of poliomyelitis, acute stem encephalitis, encephalomyocarditis and aseptic meningitis. The studies completely rules out the participation of polioviruses and provided comprehensive evidence for the etiological role of a peculiar enterovirus subsequently identified as enterovirus (EV) type 71 known in the literature since 1974. Altogether, in 1975 and 1976 from 65 cases of poliomyelitis-like disease (PLD) 92 strains of EV71 were isolated, including 37 strains from the brain and medulla, 1 from the cerebrospinal fluid, 10 from mesenterial lymph nodes and tonsils and 44 from faeces. In addition, in 282 convalescent cases of the disease, diagnostic seroconversion or high titers of antibody to this virus were demonstrated. The most successful virus isolation was achieved by inoculation of green monkey kidney cell cultures and newborn white mice. Bulgarian strains of enterovirus 71 regularly caused paralysis in monkeys and morphological poliomyelitis-like lesions in their CNS, and paralysis and myositis with Zenker necrosis in newborn white mice, cotton rats, Syrian hamsters, and 3-week-old cotton rats. The diseased rodents had much more virus in their mucles than in brains."}
{"id": "PMID:228640", "title": "Cytogenetic analysis of the sensitivity to anti-viral and anti-cell growth activities of human fibroblast interferon in aneuploid human tumor cell lines. Brief report.", "content": "The ability of human fibroblast interferon to suppress colony formation and papovavirus T-antigen expression in six human tumor cell lines did not appear to correlate with their content of chromosomes 16 and 21. Additional factors or chromosomes may be involved in the manifestation of interferon action in aneuploid cells.", "contents": "Cytogenetic analysis of the sensitivity to anti-viral and anti-cell growth activities of human fibroblast interferon in aneuploid human tumor cell lines. Brief report. The ability of human fibroblast interferon to suppress colony formation and papovavirus T-antigen expression in six human tumor cell lines did not appear to correlate with their content of chromosomes 16 and 21. Additional factors or chromosomes may be involved in the manifestation of interferon action in aneuploid cells."}
{"id": "PMID:228641", "title": "Investigation of physicochemical properties of Bulgarian strain 258 of enterovirus type 71. Brief report.", "content": "In the present report some general physicochemical properties and RNA characteristics of strain 258 of enterovirus (EV) 71, isolated in 1975 from cases of poliomyelitis-like disease in Bulgaria (1), are described. It is concluded, that the features of the virus are consistent with the previous identification, based on biological studies, of this virus strain as a member of enterovirus subgroup of picornaviridae family.", "contents": "Investigation of physicochemical properties of Bulgarian strain 258 of enterovirus type 71. Brief report. In the present report some general physicochemical properties and RNA characteristics of strain 258 of enterovirus (EV) 71, isolated in 1975 from cases of poliomyelitis-like disease in Bulgaria (1), are described. It is concluded, that the features of the virus are consistent with the previous identification, based on biological studies, of this virus strain as a member of enterovirus subgroup of picornaviridae family."}
{"id": "PMID:228642", "title": "Candida pachymeningitis with multiple cranial nerve pareses.", "content": "A 66-year-old woman complained of right-sided headache and was found to have progressive dysfunction of cranial nerves V and VIII through XII on the right side. At autopsy, there was a granulomatous pachymengitis involving the floor of the right middle and posterior cranial fossae due to Candida tropicalis infection. Inflammatory tissue compressed the clinically affected cranial nerves.", "contents": "Candida pachymeningitis with multiple cranial nerve pareses. A 66-year-old woman complained of right-sided headache and was found to have progressive dysfunction of cranial nerves V and VIII through XII on the right side. At autopsy, there was a granulomatous pachymengitis involving the floor of the right middle and posterior cranial fossae due to Candida tropicalis infection. Inflammatory tissue compressed the clinically affected cranial nerves."}
{"id": "PMID:228643", "title": "Nucleic acid homology studies of viral nucleic acids in idiopathic Parkinson's disease.", "content": "Reassociation kinetics analyses with radioiodinated herpes simplex type 1 DNA and influenza A/NWS RNA were performed in the presence of tissue nucleic acids from defined loci of the brains of nine patients with idiopathic Parkinson's disease, one normal control brain, and the brains of uninfected mice or mice infected with either herpes simplex type 1 virus or influenza A/NWS virus. Herpes simplex type 1 DNA was detected by an increased reassociation rate in the herpes simplex type 1 virus-infected mouse brains. Influenza A/NWS RNA was detected by reassociation in the influenza A/NWS virus-infected mouse brains. Experimental limits for the detection of homologous nucleic acids are given for each separate experiment with human or mouse tissue. Within these detection limits, nucleic acids complementary to herpes simplex type 1 DNA or influenza A/NWS RNA were not detected in any of the brains of patients with idiopathic Parkinson's disease.", "contents": "Nucleic acid homology studies of viral nucleic acids in idiopathic Parkinson's disease. Reassociation kinetics analyses with radioiodinated herpes simplex type 1 DNA and influenza A/NWS RNA were performed in the presence of tissue nucleic acids from defined loci of the brains of nine patients with idiopathic Parkinson's disease, one normal control brain, and the brains of uninfected mice or mice infected with either herpes simplex type 1 virus or influenza A/NWS virus. Herpes simplex type 1 DNA was detected by an increased reassociation rate in the herpes simplex type 1 virus-infected mouse brains. Influenza A/NWS RNA was detected by reassociation in the influenza A/NWS virus-infected mouse brains. Experimental limits for the detection of homologous nucleic acids are given for each separate experiment with human or mouse tissue. Within these detection limits, nucleic acids complementary to herpes simplex type 1 DNA or influenza A/NWS RNA were not detected in any of the brains of patients with idiopathic Parkinson's disease."}
{"id": "PMID:228644", "title": "Dibutyryl cyclic adenosine 3',5'-monophosphate: its role in regulation of cat brain extracellular fluid.", "content": "The role of dibutyryl cyclic adenosine 3',5'-monophosphate (db cAMP) in influencing the water content of the cat's gray and white matter was evaluated by intracoritcal injection of 20 micrio L of 2 x 10(-1) to 2 x 10(-6)M solution of db cAMP. Cholera toxin, a stimulator of adenylate cyclase, also was tested. Concentrations of db cAMP less than 10(-3)M failed to produce significant change in brain water content, while concentrations greater than 10(-2)M produced 31.5% +/- 8% and 17.3% +/- 3.6% increases in white matter volume, respectively (P less than .05). Cholera toxin did not increase brain water levels. These results are discussed in relation to the pathophysiology of brain edema.", "contents": "Dibutyryl cyclic adenosine 3',5'-monophosphate: its role in regulation of cat brain extracellular fluid. The role of dibutyryl cyclic adenosine 3',5'-monophosphate (db cAMP) in influencing the water content of the cat's gray and white matter was evaluated by intracoritcal injection of 20 micrio L of 2 x 10(-1) to 2 x 10(-6)M solution of db cAMP. Cholera toxin, a stimulator of adenylate cyclase, also was tested. Concentrations of db cAMP less than 10(-3)M failed to produce significant change in brain water content, while concentrations greater than 10(-2)M produced 31.5% +/- 8% and 17.3% +/- 3.6% increases in white matter volume, respectively (P less than .05). Cholera toxin did not increase brain water levels. These results are discussed in relation to the pathophysiology of brain edema."}
{"id": "PMID:228646", "title": "Aspirin, cyclophosphamide, and dexamethasone effects on experimental secondary herpes simplex uveitis.", "content": "The effects of aspirin, cyclophosphamide, and dexamethasone on secondary herpes simplex uveitis were studied in rabbits. Neither daily treatment with aspirin (rectal suppositories, 650 mg begun 24 hours before challenge) nor cyclophosphamide injections every two days (80 mg begun eight days before challenge) had any effect on the severity of the uveitis, on the rise in intraocular pressure (IOP), or on the host's immune responses. As in the control animals, infectious herpes simplex virus (HSV) could not be isolated from iris tissues of either aspirin- or cyclophosphamide-treated rabbits. On the other hand, twice-daily treatment with topical dexamethasone (0.1% drops begun 24 hours before challenge) lessened the severity of the uveitis appreciably and suppressed the rise in IOP, but iris tissues yielded infectious HSV in two of ten eyes. Although the dexamethasone had no effect on the neutralizing-antibody or macrophage migration inhibition factor, it markedly suppressed the chemotactic activity of the aqueous humor for both polymorphonuclear leukocytes and macrophages.", "contents": "Aspirin, cyclophosphamide, and dexamethasone effects on experimental secondary herpes simplex uveitis. The effects of aspirin, cyclophosphamide, and dexamethasone on secondary herpes simplex uveitis were studied in rabbits. Neither daily treatment with aspirin (rectal suppositories, 650 mg begun 24 hours before challenge) nor cyclophosphamide injections every two days (80 mg begun eight days before challenge) had any effect on the severity of the uveitis, on the rise in intraocular pressure (IOP), or on the host's immune responses. As in the control animals, infectious herpes simplex virus (HSV) could not be isolated from iris tissues of either aspirin- or cyclophosphamide-treated rabbits. On the other hand, twice-daily treatment with topical dexamethasone (0.1% drops begun 24 hours before challenge) lessened the severity of the uveitis appreciably and suppressed the rise in IOP, but iris tissues yielded infectious HSV in two of ten eyes. Although the dexamethasone had no effect on the neutralizing-antibody or macrophage migration inhibition factor, it markedly suppressed the chemotactic activity of the aqueous humor for both polymorphonuclear leukocytes and macrophages."}
{"id": "PMID:228647", "title": "Emerging patterns of hepatitis B chronic liver disease in Australia.", "content": "Until now, the hepatitis B virus has been thought to play a minor role in the aetiology of chronic liver disease in Australia. This is a report of 21 patients with cirrhosis and/or primary hepatocellular carcinoma with hepatitis B antigenaemia. Primary hepatocellular carcinoma occurred in six patients, five of whom had underlying cirrhosis. The disease occurred mainly in non-Australian born males, and was not often associated with a previous history of hepatitis. The death of 16 patients within 12 months of presentation is in contrast to previous concepts of the benign nature of hepatitis B associated cirrhosis.", "contents": "Emerging patterns of hepatitis B chronic liver disease in Australia. Until now, the hepatitis B virus has been thought to play a minor role in the aetiology of chronic liver disease in Australia. This is a report of 21 patients with cirrhosis and/or primary hepatocellular carcinoma with hepatitis B antigenaemia. Primary hepatocellular carcinoma occurred in six patients, five of whom had underlying cirrhosis. The disease occurred mainly in non-Australian born males, and was not often associated with a previous history of hepatitis. The death of 16 patients within 12 months of presentation is in contrast to previous concepts of the benign nature of hepatitis B associated cirrhosis."}
{"id": "PMID:228648", "title": "Maternal immunosuppression and cytomegalovirus infection of the fetus.", "content": "Prenatal cytomegalovirus (CMV) infection associated with severe brain damage was detected in an infant whose mother had been treated with prednisolone and azathioprine for systemic lupus erythematosus (SLE). Serology showed that maternal CMV infection had been acquired at least four months before pregnancy. Screening for CMV infection in pregnant women receiving immunosuppressive drugs is recommended.", "contents": "Maternal immunosuppression and cytomegalovirus infection of the fetus. Prenatal cytomegalovirus (CMV) infection associated with severe brain damage was detected in an infant whose mother had been treated with prednisolone and azathioprine for systemic lupus erythematosus (SLE). Serology showed that maternal CMV infection had been acquired at least four months before pregnancy. Screening for CMV infection in pregnant women receiving immunosuppressive drugs is recommended."}
{"id": "PMID:228649", "title": "Autoradiographic localization of binding sites for follicle stimulating hormone (FSH) in the boar testis.", "content": "The tubular localization of binding sites for 125I-FSH is demonstrated in vitro by the autoradiography on frozen sections of boar-testis. The uniform distribution of silver grains throughout the seminiferous epithelium suggests the presence of receptors for FSH also in the adluminal compartment. Similar results have been obtained using rat testis.", "contents": "Autoradiographic localization of binding sites for follicle stimulating hormone (FSH) in the boar testis. The tubular localization of binding sites for 125I-FSH is demonstrated in vitro by the autoradiography on frozen sections of boar-testis. The uniform distribution of silver grains throughout the seminiferous epithelium suggests the presence of receptors for FSH also in the adluminal compartment. Similar results have been obtained using rat testis."}
{"id": "PMID:228650", "title": "Studies on enzymes of collagen biosynthesis and the synthesis of hydroxyproline in macrophages and mast cells.", "content": "The activities of four intracellular enzymes of collagen biosynthesis were assayed in freshly isolated rat peritoneal macrophages and mast cells and compared with the same enzymes in freshly isolated chick-embryo tendon cells. The macrophages were found to contain activities of all four enzymes, those of prolyl and lysyl hydroxylase being 7 and 12% respectively of those in the tendon cells when expressed per cell or 3 and 4% when expressed per unit of soluble cell protein. The corresponding values for hydroxylysyl galactosyltransferase and galactosylhydroxylysyl glucosyltransferase activities were about 82 and 68% or 32 and 24% respectively. When the macrophages were incubated in suspension with [(14)C]proline, they synthesized a small but significant amount of non-diffusible hydroxy[(14)C]proline. The synthesis per cell was only about 0.1% of that formed by the tendon cells, and its distribution between the cells and the medium also differed from that in the tendon cells. The hydroxy[(14)C]proline synthesized by the macrophages may be present in the Clq subcomponent of the complement, but its amount was too small to allow any characterization of the protein. All four enzyme activities, and in particular the two hydroxylysyl glycosyltransferase activities, seem to be present in macrophages in a large excess compared with the very low rate of synthesis of hydroxy-proline-containing polypeptide chains. The mast cell extract was found to inhibit all four enzyme activities, but even when corrected for this inhibition, prolyl and lysyl hydroxylase activities in the mast cells were less than 0.08% and the two hydroxylysyl glycosyltransferase activities less than 1% of those in the tendon cells. The intracellular enzyme pattern of collagen biosynthesis in the mast cells is thus completely or virtually completely repressed.", "contents": "Studies on enzymes of collagen biosynthesis and the synthesis of hydroxyproline in macrophages and mast cells. The activities of four intracellular enzymes of collagen biosynthesis were assayed in freshly isolated rat peritoneal macrophages and mast cells and compared with the same enzymes in freshly isolated chick-embryo tendon cells. The macrophages were found to contain activities of all four enzymes, those of prolyl and lysyl hydroxylase being 7 and 12% respectively of those in the tendon cells when expressed per cell or 3 and 4% when expressed per unit of soluble cell protein. The corresponding values for hydroxylysyl galactosyltransferase and galactosylhydroxylysyl glucosyltransferase activities were about 82 and 68% or 32 and 24% respectively. When the macrophages were incubated in suspension with [(14)C]proline, they synthesized a small but significant amount of non-diffusible hydroxy[(14)C]proline. The synthesis per cell was only about 0.1% of that formed by the tendon cells, and its distribution between the cells and the medium also differed from that in the tendon cells. The hydroxy[(14)C]proline synthesized by the macrophages may be present in the Clq subcomponent of the complement, but its amount was too small to allow any characterization of the protein. All four enzyme activities, and in particular the two hydroxylysyl glycosyltransferase activities, seem to be present in macrophages in a large excess compared with the very low rate of synthesis of hydroxy-proline-containing polypeptide chains. The mast cell extract was found to inhibit all four enzyme activities, but even when corrected for this inhibition, prolyl and lysyl hydroxylase activities in the mast cells were less than 0.08% and the two hydroxylysyl glycosyltransferase activities less than 1% of those in the tendon cells. The intracellular enzyme pattern of collagen biosynthesis in the mast cells is thus completely or virtually completely repressed."}
{"id": "PMID:228651", "title": "Tri-iodothyronine-induced increase in rat liver nuclear thyroid-hormone receptors associated with increased mitochondrial alpha-glycerophosphate dehydrogenase activity.", "content": "The effect of tri-iodothyronine injection on the nuclear tri-iodothyronine receptor (putative thyroid-hormone receptor) was examined in rat liver. Nuclear receptors were extracted from isolated nuclei with 0.4 M-KCl, and their association constants (Ka) and maximal binding capacities (Cmax.) were determined by Scatchard analyses with and without correction for the endogenous hormone. The amount of endogenous tri-iodothyronine bound to non-histone protein was estimated on the basis of the specific radio-activity of [125I]tri-iodothyronine injected 2 h before the rats were killed. It was demonstrated that Cmax. of the nuclear receptors was 2.5-fold higher in severely hyperthyroid than in hypothyroid rats. However, irrespective of the thyroid status, the Ka of the receptors remained unchanged when corrected for endogenous tri-iodothyronine bound to non-histone protein. The validity of the correction was supported by experiments in vitro in which nuclear receptors were preincubated with unlabelled tri-iodothyronine. The increase in Cmax. of nuclear receptors was directly related to mitochondrial alpha-glycerophosphate dehydrogenase activity. These results suggest a hormonal modulation of the nuclear receptors which is associated with hormonal action.", "contents": "Tri-iodothyronine-induced increase in rat liver nuclear thyroid-hormone receptors associated with increased mitochondrial alpha-glycerophosphate dehydrogenase activity. The effect of tri-iodothyronine injection on the nuclear tri-iodothyronine receptor (putative thyroid-hormone receptor) was examined in rat liver. Nuclear receptors were extracted from isolated nuclei with 0.4 M-KCl, and their association constants (Ka) and maximal binding capacities (Cmax.) were determined by Scatchard analyses with and without correction for the endogenous hormone. The amount of endogenous tri-iodothyronine bound to non-histone protein was estimated on the basis of the specific radio-activity of [125I]tri-iodothyronine injected 2 h before the rats were killed. It was demonstrated that Cmax. of the nuclear receptors was 2.5-fold higher in severely hyperthyroid than in hypothyroid rats. However, irrespective of the thyroid status, the Ka of the receptors remained unchanged when corrected for endogenous tri-iodothyronine bound to non-histone protein. The validity of the correction was supported by experiments in vitro in which nuclear receptors were preincubated with unlabelled tri-iodothyronine. The increase in Cmax. of nuclear receptors was directly related to mitochondrial alpha-glycerophosphate dehydrogenase activity. These results suggest a hormonal modulation of the nuclear receptors which is associated with hormonal action."}
{"id": "PMID:228652", "title": "Sequential changes in rat liver nuclear tri-iodothyronine receptors and mitochondrial alpha-glycerophosphate dehydrogenase activity after administration of tri-iodothyronine.", "content": "The dynamics of the induction of nuclear tri-iodothyronine receptors and mitochondrial alpha-glycerophosphate dehydrogenase were studied in rat liver after a single injection of tri-iodothyronine. The maximal binding capacity (C(max.)) and association constant (K(a)) of the nuclear receptors were determined by Scatchard analyses with and without correction for the endogenous tri-iodothyronine measured by radioimmunoassay. The administration of tri-iodothyronine induced sequential increases in the concentration of nuclear receptors and alpha-glycerophosphate dehydrogenase activity in the liver. The nuclear-receptor concentration was increased to 2.5 times that in the hypothyroid rat 1 day after the administration of hormone, and then decreased, with a half-life of about 2 days. alpha-Glycerophosphate dehydrogenase activity changed in parallel with the nuclear-receptor concentration, showing a delayed response. The total amount of non-histone protein in the liver was significantly increased 3 days after the administration. It seems likely therefore that the tri-iodothyronine-induced increase in nuclear-receptor concentration is responsible, at least in part, for the induction of this enzyme. The possibility is also suggested that nuclear receptors may be one of the non-histone proteins selectively synthesized at an early stage of the hormonal stimulation. Throughout the time course, the K(a) values of the nuclear receptors for tri-iodothyronine remained unchanged, when corrected for endogenous tri-iodothyronine bound to the non-histone proteins, although they were apparently changed when the correction was not made. The results obtained provide further evidence for hormonal modulation of the nuclear receptors which is closely linked with the hormonal effect.", "contents": "Sequential changes in rat liver nuclear tri-iodothyronine receptors and mitochondrial alpha-glycerophosphate dehydrogenase activity after administration of tri-iodothyronine. The dynamics of the induction of nuclear tri-iodothyronine receptors and mitochondrial alpha-glycerophosphate dehydrogenase were studied in rat liver after a single injection of tri-iodothyronine. The maximal binding capacity (C(max.)) and association constant (K(a)) of the nuclear receptors were determined by Scatchard analyses with and without correction for the endogenous tri-iodothyronine measured by radioimmunoassay. The administration of tri-iodothyronine induced sequential increases in the concentration of nuclear receptors and alpha-glycerophosphate dehydrogenase activity in the liver. The nuclear-receptor concentration was increased to 2.5 times that in the hypothyroid rat 1 day after the administration of hormone, and then decreased, with a half-life of about 2 days. alpha-Glycerophosphate dehydrogenase activity changed in parallel with the nuclear-receptor concentration, showing a delayed response. The total amount of non-histone protein in the liver was significantly increased 3 days after the administration. It seems likely therefore that the tri-iodothyronine-induced increase in nuclear-receptor concentration is responsible, at least in part, for the induction of this enzyme. The possibility is also suggested that nuclear receptors may be one of the non-histone proteins selectively synthesized at an early stage of the hormonal stimulation. Throughout the time course, the K(a) values of the nuclear receptors for tri-iodothyronine remained unchanged, when corrected for endogenous tri-iodothyronine bound to the non-histone proteins, although they were apparently changed when the correction was not made. The results obtained provide further evidence for hormonal modulation of the nuclear receptors which is closely linked with the hormonal effect."}
{"id": "PMID:228653", "title": "Effect of vitamin D deficiency on bone formation in the chick.", "content": "1. The process of diaphyseal bone formation can be investigated by studying the rate of incorporation of radioactive precursors, administered in vivo into bone fractions of increasing density. 2. In the 4-week-old vitamin D-treated chick most of the osteoid becomes calcified within 12h and almost all within 2 days. The low-density calcified phase that is formed is converted into a higher density form and within 7 days the greater proportion of the calcified tissue is in the higher density form. 3. In the vitamin D-deficient chick of similar age the rate of calcification of osteoid is decreased, as is the rate of conversion into the higher density phase with the resultant accumulation of the lower density calcified form. 4. The higher density phase probably corresponds to hydroxyapatite and the lower density one to the ACP-pase described by Termine & Posner [(1967) Calcif. Tissue Res. 1, 8--23]. 5. The disorder in the process of calcification seems to be unrelated to the alteration in blood Ca2+ and phosphate concentrations, but related to the presence or absence of cholecalciferol.", "contents": "Effect of vitamin D deficiency on bone formation in the chick. 1. The process of diaphyseal bone formation can be investigated by studying the rate of incorporation of radioactive precursors, administered in vivo into bone fractions of increasing density. 2. In the 4-week-old vitamin D-treated chick most of the osteoid becomes calcified within 12h and almost all within 2 days. The low-density calcified phase that is formed is converted into a higher density form and within 7 days the greater proportion of the calcified tissue is in the higher density form. 3. In the vitamin D-deficient chick of similar age the rate of calcification of osteoid is decreased, as is the rate of conversion into the higher density phase with the resultant accumulation of the lower density calcified form. 4. The higher density phase probably corresponds to hydroxyapatite and the lower density one to the ACP-pase described by Termine & Posner [(1967) Calcif. Tissue Res. 1, 8--23]. 5. The disorder in the process of calcification seems to be unrelated to the alteration in blood Ca2+ and phosphate concentrations, but related to the presence or absence of cholecalciferol."}
{"id": "PMID:228654", "title": "Characterization of cyanide-insensitive respiration in mitochondria and submitochondrial particles of Moniliella tomentosa.", "content": "Mitochondria and submitochondrial particles of the osmophilic yeast-like fungus Moniliella tomentosa may respire by means of two pathways: a normal cytochrome pathway, sensitive to cyanide and antimycin A, and an alternative pathway, which is insensitive to these inhibitors but is specifically inhibited by salicylhydroxamic acid. The affinities of both oxidases for succinate and NADH as substrates, for O(2) as terminal electron acceptor, and for AMP as stimulator of the alternative oxidase were determined. 1. Submitochondrial particles of M. tomentosa may also respire by means of a cyanide-sensitive and/or cyanide-insensitive system. 2. The activities of both oxidases as compared with the total activity are roughly the same in submitochondrial particles as in the original mitochondria. 3. The terminal oxidase of the cyanide-insensitive pathway requires a 10-fold higher O(2) concentration for saturation than does cytochrome c oxidase. 4. The apparent K(m) for succinate is about 3 times higher for the alternative than for the normal oxidase when measured in mitochondria, and 4-10 times higher when measured in submitochondrial particles. The apparent K(m) for NADH is roughly the same for both oxidases. 5. The apparent K(m) values of both oxidases for succinate are always lower in submitochondrial particles than in mitochondria. 6. The apparent K(m) for AMP, acting as a stimulator of the alternative oxidase, is the same (25mum) in mitochondria as in sub-mitochondrial particles. These results are discussed in the light of the structure and localization of the components of the alternative oxidase.", "contents": "Characterization of cyanide-insensitive respiration in mitochondria and submitochondrial particles of Moniliella tomentosa. Mitochondria and submitochondrial particles of the osmophilic yeast-like fungus Moniliella tomentosa may respire by means of two pathways: a normal cytochrome pathway, sensitive to cyanide and antimycin A, and an alternative pathway, which is insensitive to these inhibitors but is specifically inhibited by salicylhydroxamic acid. The affinities of both oxidases for succinate and NADH as substrates, for O(2) as terminal electron acceptor, and for AMP as stimulator of the alternative oxidase were determined. 1. Submitochondrial particles of M. tomentosa may also respire by means of a cyanide-sensitive and/or cyanide-insensitive system. 2. The activities of both oxidases as compared with the total activity are roughly the same in submitochondrial particles as in the original mitochondria. 3. The terminal oxidase of the cyanide-insensitive pathway requires a 10-fold higher O(2) concentration for saturation than does cytochrome c oxidase. 4. The apparent K(m) for succinate is about 3 times higher for the alternative than for the normal oxidase when measured in mitochondria, and 4-10 times higher when measured in submitochondrial particles. The apparent K(m) for NADH is roughly the same for both oxidases. 5. The apparent K(m) values of both oxidases for succinate are always lower in submitochondrial particles than in mitochondria. 6. The apparent K(m) for AMP, acting as a stimulator of the alternative oxidase, is the same (25mum) in mitochondria as in sub-mitochondrial particles. These results are discussed in the light of the structure and localization of the components of the alternative oxidase."}
{"id": "PMID:228655", "title": "Electron-paramagnetic-resonance measurements of the electron-transfer components of the reaction centre of Rhodopseudomonas viridis. Oxidation--reduction potentials and interactions of the electron acceptors.", "content": "Oxidation-reduction potentiometry was carried out on Rhodopseudomonas viridis chromatophores. Measurements of e.p.r. signals of the semiquinone-iron type at g=1.82 have revealed a more complex situation than previously reported. The presence of three different components is indicated. The midpoint potential (E(m)) of the primary acceptor quinone/semiquinone couple was found to be approx. -165mV at pH10, with a pK being reached at around pH7.5. The primary acceptor also accepts a second electron with an E(m) of -525mV, but this redox transition exhibits a hysteresis effect. Interaction effects indicate the presence of another component with E(m) values at pH10 of approx. -165mV (pK reached at around pH7.5) for single reduction and -350mV (pK at pH10 or greater) for double reduction. It is suggested that this component is the secondary acceptor. Another semiquinone-iron-type component which gives a g=1.82 signal is also present. This component is distinguishable from the primary acceptor by its e.p.r. spectrum, which shows a double peak at g=1.82 and a g(x) line at g=1.76. This component has E(m) values at pH10 for single and double reduction of -15mV and approx. -150mV respectively. Both of these E(m) values are pH-dependent. The presence of an interaction between this component and the photoreduced primary acceptor indicates the close proximity of these components. However, the midpoint potential of this component indicates a function as a secondary electron-transport component rather than an electron acceptor in the reaction centre. The dependence of the bacteriopheophytin intermediate (I) doublet e.p.r. signal on the presence of the semiquinone-iron form of the primary acceptor is demonstrated. The midpoint potential of the I/I(-) couple is estimated to be lower than -600mV.", "contents": "Electron-paramagnetic-resonance measurements of the electron-transfer components of the reaction centre of Rhodopseudomonas viridis. Oxidation--reduction potentials and interactions of the electron acceptors. Oxidation-reduction potentiometry was carried out on Rhodopseudomonas viridis chromatophores. Measurements of e.p.r. signals of the semiquinone-iron type at g=1.82 have revealed a more complex situation than previously reported. The presence of three different components is indicated. The midpoint potential (E(m)) of the primary acceptor quinone/semiquinone couple was found to be approx. -165mV at pH10, with a pK being reached at around pH7.5. The primary acceptor also accepts a second electron with an E(m) of -525mV, but this redox transition exhibits a hysteresis effect. Interaction effects indicate the presence of another component with E(m) values at pH10 of approx. -165mV (pK reached at around pH7.5) for single reduction and -350mV (pK at pH10 or greater) for double reduction. It is suggested that this component is the secondary acceptor. Another semiquinone-iron-type component which gives a g=1.82 signal is also present. This component is distinguishable from the primary acceptor by its e.p.r. spectrum, which shows a double peak at g=1.82 and a g(x) line at g=1.76. This component has E(m) values at pH10 for single and double reduction of -15mV and approx. -150mV respectively. Both of these E(m) values are pH-dependent. The presence of an interaction between this component and the photoreduced primary acceptor indicates the close proximity of these components. However, the midpoint potential of this component indicates a function as a secondary electron-transport component rather than an electron acceptor in the reaction centre. The dependence of the bacteriopheophytin intermediate (I) doublet e.p.r. signal on the presence of the semiquinone-iron form of the primary acceptor is demonstrated. The midpoint potential of the I/I(-) couple is estimated to be lower than -600mV."}
{"id": "PMID:228656", "title": "Protein phosphorylation in human peripheral blood lymphocytes. Subcellular distribution and partial characterization of adenosine 3':5'-cyclic monophosphate-dependent protein kinase.", "content": "Cytoplasmic and membrane fractions prepared from human peripheral-blood lymphocytes both contained cyclic AMP-dependent protein kinase activity and endogenous protein kinase substrates. Protein kinase activity in the particulate fractions was not eluted with 0.25 M-NaCl, suggesting that it was not derived from non-specifically absorbed soluble cytoplasmic protein kinase. Nor was the particulate protein kinase activity eluted by treatment with cyclic AMP, suggesting that the catalytic subunit is membrane-bound and arguing against cyclic AMP-induced translocation of particulate activity. Cyclic AMP-dependent protein-phosphorylating activity in the cytoplasmic fraction was highly sensitive to inhibition by Mn2+, and was co-eluted from DEAE-cellulose primarily with type-I rabbit skeletal-muscle kinase. Cyclic AMP-dependent phosphorylating activity in the plasma-membrane fractions was stimulated at low [Mn2+] and inhibited only at high [Mn2+]. When solubilized with Nonidet P-40, plasma-membrane protein kinase was co-eluted from DEAE-cellulose with type-II rabbit muscle kinase. These differences, together with the strong association of the particulate kinases with the particulate fraction, suggest the possibility of compartmentalized protein phosphorylation in intact lymphocytes.", "contents": "Protein phosphorylation in human peripheral blood lymphocytes. Subcellular distribution and partial characterization of adenosine 3':5'-cyclic monophosphate-dependent protein kinase. Cytoplasmic and membrane fractions prepared from human peripheral-blood lymphocytes both contained cyclic AMP-dependent protein kinase activity and endogenous protein kinase substrates. Protein kinase activity in the particulate fractions was not eluted with 0.25 M-NaCl, suggesting that it was not derived from non-specifically absorbed soluble cytoplasmic protein kinase. Nor was the particulate protein kinase activity eluted by treatment with cyclic AMP, suggesting that the catalytic subunit is membrane-bound and arguing against cyclic AMP-induced translocation of particulate activity. Cyclic AMP-dependent protein-phosphorylating activity in the cytoplasmic fraction was highly sensitive to inhibition by Mn2+, and was co-eluted from DEAE-cellulose primarily with type-I rabbit skeletal-muscle kinase. Cyclic AMP-dependent phosphorylating activity in the plasma-membrane fractions was stimulated at low [Mn2+] and inhibited only at high [Mn2+]. When solubilized with Nonidet P-40, plasma-membrane protein kinase was co-eluted from DEAE-cellulose with type-II rabbit muscle kinase. These differences, together with the strong association of the particulate kinases with the particulate fraction, suggest the possibility of compartmentalized protein phosphorylation in intact lymphocytes."}
{"id": "PMID:228657", "title": "Protein phosphorlyation in human peripheral blood lymphocytes. Phosphorylation of endogenous plasma membrane and cytoplasmic proteins.", "content": "Phosphorylation of endogenous proteins in subcellular fractions of human peripheral-blood lymphocytes was studied by one- and two-dimensional polyacrylamide-gel electrophoresis. Studies using extensively purified subcellular fractions indicated that the endogenous phosphorylating activity in the particulate fractions was derived primarily from the plasma membrane. Electrophoresis of (32)P-labelled subcellular fractions in two dimensions [O'Farrell (1975) J. Biol. Chem.250, 4007-4021] provided much greater resolution of the endogenous phosphoproteins than electrophoresis in one dimension, facilitating their excision from gels for quantification of (32)P content. More than 100 cytoplasmic and 20 plasma-membrane phosphorylated species were observed. Phosphorylation of more than 10 cytoplasmic proteins was absolutely dependent on cyclic AMP. In the plasma membrane, cyclic AMP-dependent phosphoproteins were observed with mol.wts. of 42000, 42000, 80000 and 90000 and pI values of 6.1, 6.3, 6.25 and 6.5 respectively. Phosphorylation of endogenous cytoplasmic and plasma-membrane proteins was rapid with t((1/2))=5-12s at 25 degrees C. Between 40 and 70% of the (32)P was recovered as phosphoserine and phosphothreonine when acid hydrolysates of isolated plasma-membrane phosphoproteins were analysed by high-voltage paper electrophoresis. The presence of cyclic AMP-dependent protein kinase and endogenous phosphate-acceptor proteins in the plasma membranes of lymphocytes provides a mechanism by which these cells might respond to plasma-membrane pools of cyclic AMP generated in response to stimulation by mitogens or physiological modulators of lymphocyte function.", "contents": "Protein phosphorlyation in human peripheral blood lymphocytes. Phosphorylation of endogenous plasma membrane and cytoplasmic proteins. Phosphorylation of endogenous proteins in subcellular fractions of human peripheral-blood lymphocytes was studied by one- and two-dimensional polyacrylamide-gel electrophoresis. Studies using extensively purified subcellular fractions indicated that the endogenous phosphorylating activity in the particulate fractions was derived primarily from the plasma membrane. Electrophoresis of (32)P-labelled subcellular fractions in two dimensions [O'Farrell (1975) J. Biol. Chem.250, 4007-4021] provided much greater resolution of the endogenous phosphoproteins than electrophoresis in one dimension, facilitating their excision from gels for quantification of (32)P content. More than 100 cytoplasmic and 20 plasma-membrane phosphorylated species were observed. Phosphorylation of more than 10 cytoplasmic proteins was absolutely dependent on cyclic AMP. In the plasma membrane, cyclic AMP-dependent phosphoproteins were observed with mol.wts. of 42000, 42000, 80000 and 90000 and pI values of 6.1, 6.3, 6.25 and 6.5 respectively. Phosphorylation of endogenous cytoplasmic and plasma-membrane proteins was rapid with t((1/2))=5-12s at 25 degrees C. Between 40 and 70% of the (32)P was recovered as phosphoserine and phosphothreonine when acid hydrolysates of isolated plasma-membrane phosphoproteins were analysed by high-voltage paper electrophoresis. The presence of cyclic AMP-dependent protein kinase and endogenous phosphate-acceptor proteins in the plasma membranes of lymphocytes provides a mechanism by which these cells might respond to plasma-membrane pools of cyclic AMP generated in response to stimulation by mitogens or physiological modulators of lymphocyte function."}
{"id": "PMID:228658", "title": "Changing pattern of cyclic AMP-binding proteins during germination of Mucor racemosus sporangiospores.", "content": "Interation of cyclic AMP with a profoundly changing pattern of specific binding proteins was shown during aerobic germination of sporangiospores from the fungus Mucor racemosus. 32P-labeled 8-azido-cycli AMP, an analogue of cyclic AMP that forms a covalent linkage with the binding proteins under u.v. light, was used as the ligand. Binding proteins carrying this photoaffinity label were separated by polyacrylamide-gel electrophoresis and identified by radioautography. Equibiltrium dissociation constants (Kd) and binding-response curves in the presence of competing nucleotides were identical for both 8-azido-cyclic [32P]AMP and cyclic [3H]AMP. A quantitative binding assay with both 8-azido-cyclic [32P]AMP and cyclic [3H]AMP over the time course of sporangiospore germination indicated a parallel relationship between cyclic AMP-binding capacity and the intracellular concentrations of cyclic AMP reported in a previous study [Paznokas & Sypherd (1975) J. Bacteriol. 124, 134--139]. Both of these parameters attained transient high values at a time of development when addition of exogenous cyclic AMP prevents hyphal-germ-tube emergence. The measured Kd values did not change during sport germination.", "contents": "Changing pattern of cyclic AMP-binding proteins during germination of Mucor racemosus sporangiospores. Interation of cyclic AMP with a profoundly changing pattern of specific binding proteins was shown during aerobic germination of sporangiospores from the fungus Mucor racemosus. 32P-labeled 8-azido-cycli AMP, an analogue of cyclic AMP that forms a covalent linkage with the binding proteins under u.v. light, was used as the ligand. Binding proteins carrying this photoaffinity label were separated by polyacrylamide-gel electrophoresis and identified by radioautography. Equibiltrium dissociation constants (Kd) and binding-response curves in the presence of competing nucleotides were identical for both 8-azido-cyclic [32P]AMP and cyclic [3H]AMP. A quantitative binding assay with both 8-azido-cyclic [32P]AMP and cyclic [3H]AMP over the time course of sporangiospore germination indicated a parallel relationship between cyclic AMP-binding capacity and the intracellular concentrations of cyclic AMP reported in a previous study [Paznokas & Sypherd (1975) J. Bacteriol. 124, 134--139]. Both of these parameters attained transient high values at a time of development when addition of exogenous cyclic AMP prevents hyphal-germ-tube emergence. The measured Kd values did not change during sport germination."}
{"id": "PMID:228659", "title": "Lipid environment of gastric potassium ion-stimulated adenosine triphosphatase.", "content": "The K+-stimulated ATPase associated with the purified gastric microsomal fraction can be completely inactivated by treatment with 15% (v/v) ethanol for 60s at 37 degrees C, but not at 25 degrees C. Sequential exposure of the microsomal fraction to 15% ethanol at 25 degrees C and 37 degrees C caused release of 2.5% and 2.9% of the total membrane phospholipids respectively. Restoration of the enzyme activity was achieved by sonication with phosphatidylcholine in the presence of Mg2+, K+ and ATP, which were essential for the reconstitution. Our data suggest that the phospholipids extracted by 15% ethanol at 37 degrees C are derived primarily from the immediate lipid environment of the enzyme, and ATP, together with the metal ions, helps the partially delipidated enzyme to retain the appropriate configuration for the subsequent reconstitution.", "contents": "Lipid environment of gastric potassium ion-stimulated adenosine triphosphatase. The K+-stimulated ATPase associated with the purified gastric microsomal fraction can be completely inactivated by treatment with 15% (v/v) ethanol for 60s at 37 degrees C, but not at 25 degrees C. Sequential exposure of the microsomal fraction to 15% ethanol at 25 degrees C and 37 degrees C caused release of 2.5% and 2.9% of the total membrane phospholipids respectively. Restoration of the enzyme activity was achieved by sonication with phosphatidylcholine in the presence of Mg2+, K+ and ATP, which were essential for the reconstitution. Our data suggest that the phospholipids extracted by 15% ethanol at 37 degrees C are derived primarily from the immediate lipid environment of the enzyme, and ATP, together with the metal ions, helps the partially delipidated enzyme to retain the appropriate configuration for the subsequent reconstitution."}
{"id": "PMID:228677", "title": "Sex hormone production and action.", "content": "The mechanisms of the production of estrogens and androgens in women and men are reviewed. Extraglandular estrogen formation from circulating androgens is the principal source of estrogen in men and postmenopausal women. The amount of estrogen formed is dependent upon precursor availability and metabolic factors, such as obesity and hepatic disease. Both androgens and estrogens in the circulation of humans are bound to sex hormone binding globulin which limits their availability to target cell receptors.", "contents": "Sex hormone production and action. The mechanisms of the production of estrogens and androgens in women and men are reviewed. Extraglandular estrogen formation from circulating androgens is the principal source of estrogen in men and postmenopausal women. The amount of estrogen formed is dependent upon precursor availability and metabolic factors, such as obesity and hepatic disease. Both androgens and estrogens in the circulation of humans are bound to sex hormone binding globulin which limits their availability to target cell receptors."}
{"id": "PMID:228678", "title": "Increased collagen prolyl hydroxylase activity in the aortic wall of rabbits exposed to chronic hypoxia.", "content": "The activity of collagen prolyl hydroxylase in aortic wall was studied in rabbits exposed to chronic 10% ambient oxygen tension for 30 days. Prolyl hydroxylase in rabbit aorta was shown to be similar to the enzyme from other sources in that it required molecular oxygen, alpha-ketoglutarate, ferrous iron and ascorbate for its activity. The activity of prolyl hydroxylase was increased to 180% of controls in the intima-media samples from rabbits exposed to hypoxia. No atherosclerotic lesions could be seen in arteries of animals kept in chronic hypoxia. If the arteries of rabbits were injured with a single mechanical dilatation, the activity of prolyl hydroxylase increased more than 2-fold, as reported previously. The exposure of these animals to chronic hypoxia further elevated the prolyl hydroxylase activity.", "contents": "Increased collagen prolyl hydroxylase activity in the aortic wall of rabbits exposed to chronic hypoxia. The activity of collagen prolyl hydroxylase in aortic wall was studied in rabbits exposed to chronic 10% ambient oxygen tension for 30 days. Prolyl hydroxylase in rabbit aorta was shown to be similar to the enzyme from other sources in that it required molecular oxygen, alpha-ketoglutarate, ferrous iron and ascorbate for its activity. The activity of prolyl hydroxylase was increased to 180% of controls in the intima-media samples from rabbits exposed to hypoxia. No atherosclerotic lesions could be seen in arteries of animals kept in chronic hypoxia. If the arteries of rabbits were injured with a single mechanical dilatation, the activity of prolyl hydroxylase increased more than 2-fold, as reported previously. The exposure of these animals to chronic hypoxia further elevated the prolyl hydroxylase activity."}
{"id": "PMID:228679", "title": "Short-term egg yolk feeding in humans. Increase in apolipoprotein B and low density lipoprotein cholesterol.", "content": "In animal studies, hypercholesterolemia induced by cholesterol feeding results in the plasma cholesterol being transported by lipoproteins of lower densities. Little information is available for humans. To determine the specific lipoprotein responses to dietary cholesterol challenge in humans, four volunteer subjects ingested a liquid formula diet containing 5000 mg of egg yolk cholesterol per day for 30 days and the changes in their lipoprotein fractions were examined. The high dietary cholesterol (above the range of normal diet) was associated with marked increases in apolipoprotein B and low density lipoprotein (LDL) cholesterol levels. An elevated cholesterol : triglyceride ratio in the LDL fraction indicated that the diet altered both LDL level and composition. High density lipoprotein cholesterol and apolipoprotein AI increased slightly. Very low and intermediate density lipoprotein cholesterol and apolipoprotein E levels did not increase during the diet. Thus, high dietary cholesterol was associated with major changes in LDL level and composition, but only minor changes in the other lipoprotein fractions and suggested only minor accumulation of remnant particles.", "contents": "Short-term egg yolk feeding in humans. Increase in apolipoprotein B and low density lipoprotein cholesterol. In animal studies, hypercholesterolemia induced by cholesterol feeding results in the plasma cholesterol being transported by lipoproteins of lower densities. Little information is available for humans. To determine the specific lipoprotein responses to dietary cholesterol challenge in humans, four volunteer subjects ingested a liquid formula diet containing 5000 mg of egg yolk cholesterol per day for 30 days and the changes in their lipoprotein fractions were examined. The high dietary cholesterol (above the range of normal diet) was associated with marked increases in apolipoprotein B and low density lipoprotein (LDL) cholesterol levels. An elevated cholesterol : triglyceride ratio in the LDL fraction indicated that the diet altered both LDL level and composition. High density lipoprotein cholesterol and apolipoprotein AI increased slightly. Very low and intermediate density lipoprotein cholesterol and apolipoprotein E levels did not increase during the diet. Thus, high dietary cholesterol was associated with major changes in LDL level and composition, but only minor changes in the other lipoprotein fractions and suggested only minor accumulation of remnant particles."}
{"id": "PMID:228680", "title": "Protein content and composition of human high density lipoprotein subfractions.", "content": "High density lipoprotein (HDL) was fractionated by ion exchange column chromatography using a continuous NaCl gradient of 0.06--0.13 M. It was found that, on the basic C apoprotein content, HDL is comprised of 3 subfractions. All 3 subfractions contain apo A-I and apo A-II but the apo A-I/apo A-II ratio is different in each subfraction and in the case of subfraction c, that fraction which eluted at highest NaCl concentrations, the A-I/A-II ratio varied even within this subfraction. Subfraction a contained no C apoprotein, subfraction b contained apo C-II and apo C-III-1 but no apo C-III-2 while subfraction c contained apo C-III-2 and trace amounts of apo C-II and C-III-1. Analysis of HDL2 and HDL3 shows that both contain all 3 lipoprotein subfractions, but in differing quantities.", "contents": "Protein content and composition of human high density lipoprotein subfractions. High density lipoprotein (HDL) was fractionated by ion exchange column chromatography using a continuous NaCl gradient of 0.06--0.13 M. It was found that, on the basic C apoprotein content, HDL is comprised of 3 subfractions. All 3 subfractions contain apo A-I and apo A-II but the apo A-I/apo A-II ratio is different in each subfraction and in the case of subfraction c, that fraction which eluted at highest NaCl concentrations, the A-I/A-II ratio varied even within this subfraction. Subfraction a contained no C apoprotein, subfraction b contained apo C-II and apo C-III-1 but no apo C-III-2 while subfraction c contained apo C-III-2 and trace amounts of apo C-II and C-III-1. Analysis of HDL2 and HDL3 shows that both contain all 3 lipoprotein subfractions, but in differing quantities."}
{"id": "PMID:228681", "title": "Uptake and degradation of low density lipoproteins (LDL) by confluent, contact-inhibited bovine and human endothelial cells exposed to physiological concentrations of LDL.", "content": "Metabolism of low density lipoproteins (LDL) was studied in cultures of endothelial cells derived from bovine aorta or heart and from human umbilical veins. At low LDL concentrations nonconfluent cultures of bovine endothelial cells catabolized more LDL protein than contact-inhibited confluent cultures but this difference was reduced at high LDL concentrations. Nonconfluent human endothelial cells displayed also a higher rate of LDL degradation than their contact-inhibited counterparts, but this difference was less pronounced than in the bovine cells. Bovine endothelial cells grown in the presence of fibroblast growth factor metabolized less LDL than those cultured without fibroblast growth factor (FGF), but this difference was not consistent in the human endothelial cells. The data presented provide evidence that contact-inhibited confluent human endothelial cells are capable of catabolizing LDL when exposed to physiological concentrations of this lipoprotein.", "contents": "Uptake and degradation of low density lipoproteins (LDL) by confluent, contact-inhibited bovine and human endothelial cells exposed to physiological concentrations of LDL. Metabolism of low density lipoproteins (LDL) was studied in cultures of endothelial cells derived from bovine aorta or heart and from human umbilical veins. At low LDL concentrations nonconfluent cultures of bovine endothelial cells catabolized more LDL protein than contact-inhibited confluent cultures but this difference was reduced at high LDL concentrations. Nonconfluent human endothelial cells displayed also a higher rate of LDL degradation than their contact-inhibited counterparts, but this difference was less pronounced than in the bovine cells. Bovine endothelial cells grown in the presence of fibroblast growth factor metabolized less LDL than those cultured without fibroblast growth factor (FGF), but this difference was not consistent in the human endothelial cells. The data presented provide evidence that contact-inhibited confluent human endothelial cells are capable of catabolizing LDL when exposed to physiological concentrations of this lipoprotein."}
{"id": "PMID:228682", "title": "The effects of cholestyramine on high density lipoprotein metabolism.", "content": "This study on 4 type II hyperlipoproteinaemic subjects examines the effects of pharmacologic doses (8 g twice daily) of the bile acid sequestrant cholestyramine on the plasma distribution and chemical composition of the high density lipoprotein subfractions, HDL2 and HDL3, and describes the influence of the drug on the metabolism of the major HDL aporoteins, apolipoprotein A-I and A-II. Cholestyramine lowered plasma low density lipoprotein cholesterol (32%; P less than 0.05) without affecting the level of that lipid in very low density or high density lipoproteins. However, the plasma HDL2/HDL3 ratio and apolipoprotein A-I concentration rose significantly on treatment, while apolipoprotein A-II remained unchanged. The rise in apolipoprotein A-I derived from an increase in its synthetic rate and produced a relative enrichment of the protein with respect to apolipoprotein A-II in both HDL subfractions. These results demonstrate the cholestyramine treatment affects HDL metabolism in a way which, according to current concepts, may prove beneficial to the recipient.", "contents": "The effects of cholestyramine on high density lipoprotein metabolism. This study on 4 type II hyperlipoproteinaemic subjects examines the effects of pharmacologic doses (8 g twice daily) of the bile acid sequestrant cholestyramine on the plasma distribution and chemical composition of the high density lipoprotein subfractions, HDL2 and HDL3, and describes the influence of the drug on the metabolism of the major HDL aporoteins, apolipoprotein A-I and A-II. Cholestyramine lowered plasma low density lipoprotein cholesterol (32%; P less than 0.05) without affecting the level of that lipid in very low density or high density lipoproteins. However, the plasma HDL2/HDL3 ratio and apolipoprotein A-I concentration rose significantly on treatment, while apolipoprotein A-II remained unchanged. The rise in apolipoprotein A-I derived from an increase in its synthetic rate and produced a relative enrichment of the protein with respect to apolipoprotein A-II in both HDL subfractions. These results demonstrate the cholestyramine treatment affects HDL metabolism in a way which, according to current concepts, may prove beneficial to the recipient."}
{"id": "PMID:228683", "title": "Changes in plasma lipoproteins accompanying diet therapy in obese diabetics.", "content": "Plasma lipoprotein cholesterol and triglyceride levels were measured in 24 obese not-insulin dependent Pima Indian diabetics and 9 obese nondiabetic controls before and after 1-8 months on a 500 calorie diet. The diabetics were divided into 3 groups--severe, recent onset (n = 10), severe long-term (n = 6), and borderline (n = 8). The diet regimen resulted in weight loss and improved glucose tolerance in all of the diabetics, and insulin secretion increased in the 2 groups of severe diabetics. After the period of weight loss, total plasma cholesterol had declined greater than 20%, and LDL cholesterol decreased 25% in all diabetic groups and in the controls. In all diabetic groups, HDL cholesterol did not decline; therefore the ratio of HDL/LDL cholesterol after diet therapy was significantly increased. In the controls HDL cholesterol declined with weight loss, and the distribution of HDL/LDL cholesterol remained constant. Plasma and VLDL triglyceride levels decreased in all groups in those with initial triglyceride levels greater than 150 mg/dl. The results indicate that weight loss in not-insulin dependent diabetics not only improves glucose tolerance, but also lowerss plasma lipids and reverses the dyslipoproteinemia often associated with this disorder. This may influence the risk of arteriosclerotic heart disease in these individuals.", "contents": "Changes in plasma lipoproteins accompanying diet therapy in obese diabetics. Plasma lipoprotein cholesterol and triglyceride levels were measured in 24 obese not-insulin dependent Pima Indian diabetics and 9 obese nondiabetic controls before and after 1-8 months on a 500 calorie diet. The diabetics were divided into 3 groups--severe, recent onset (n = 10), severe long-term (n = 6), and borderline (n = 8). The diet regimen resulted in weight loss and improved glucose tolerance in all of the diabetics, and insulin secretion increased in the 2 groups of severe diabetics. After the period of weight loss, total plasma cholesterol had declined greater than 20%, and LDL cholesterol decreased 25% in all diabetic groups and in the controls. In all diabetic groups, HDL cholesterol did not decline; therefore the ratio of HDL/LDL cholesterol after diet therapy was significantly increased. In the controls HDL cholesterol declined with weight loss, and the distribution of HDL/LDL cholesterol remained constant. Plasma and VLDL triglyceride levels decreased in all groups in those with initial triglyceride levels greater than 150 mg/dl. The results indicate that weight loss in not-insulin dependent diabetics not only improves glucose tolerance, but also lowerss plasma lipids and reverses the dyslipoproteinemia often associated with this disorder. This may influence the risk of arteriosclerotic heart disease in these individuals."}
{"id": "PMID:228684", "title": "Pronounced lipoprotein lipid reduction obtained by combined lipid-lowering treatment in patients with atherosclerotic disease.", "content": "The feasibility of reducing serum lipoprotein levels in patients with atherosclerotic disease by combining diet, clofibrate and nicotinic acid (niceritrol) has been investigated. An additive lipid-lowering effect of diet and the two drugs was demonstrated. It was possible to reduce the serum triglycerides (TG) in hypertriglyceridaemic patients by 50-60%. This corresponded to a reduction of very low density lipoprotein (VLDL) TG by 73 and 66% in patients with hyperlipoproteinaemia (HLP) type IIB and IV, respectively. In normotriglyceridaemic patients the serum TG concentration decreased by 30-40%. The serum cholesterol (Chol) concentration was reduced by 33% and the low density lipoprotein (LDL) Chol by 37% in HLP type IIA and IIB. The LDL Chol decreased by 32% in normolipoproteinaemic patients and by 21% in HLP type IV. The mean value for serum cholesterol after therapy was in all groups close to 200 mg/100 ml. In hypertriglyceridaemic patients high density lipoprotein (HDL) Chol increased by 18%. Clofibrate and niceritrol differed with regard to the effect on serum lipoprotein concentrations as well as on other metabolic parameters. Niceritrol was significantly more effective than clofibrate in lowering LDL Chol and in increasing HDL Chol. Niceritrol treatment significantly reduced the Chol/TG ratio in VLDL while no such effect was seen during clofibrate administration. The two drugs also showed significantly different effects on the fractional removal rate (K2) of triglyceride-rich lipoproteins as measured by the intravenous fat tolerance test (IVFTT). The K2 was significantly increased by clofibrate but was not affected by niceritrol treatment. The two drugs differed also with regard to the effects on serum uric acid concentration and the liver function tests. The plasma fibrinogen levels and the erythrocyte sedimentation rates were reduced during treatment with both niceritrol and clofibrate. The present study demonstrates that it is possible to obtain substantial reductions of serum lipoprotein concentrations by combining lipid-lowering diet, clofibrate and niceritrol treatment. There was an additive lipid-lowering effect of this treatment and the combination of the two drugs seemed beneficial in regard to certain possible side effects. The impact of a lipid reduction within this range on cardiovascular morbidity and mortality remains to be evaluated.", "contents": "Pronounced lipoprotein lipid reduction obtained by combined lipid-lowering treatment in patients with atherosclerotic disease. The feasibility of reducing serum lipoprotein levels in patients with atherosclerotic disease by combining diet, clofibrate and nicotinic acid (niceritrol) has been investigated. An additive lipid-lowering effect of diet and the two drugs was demonstrated. It was possible to reduce the serum triglycerides (TG) in hypertriglyceridaemic patients by 50-60%. This corresponded to a reduction of very low density lipoprotein (VLDL) TG by 73 and 66% in patients with hyperlipoproteinaemia (HLP) type IIB and IV, respectively. In normotriglyceridaemic patients the serum TG concentration decreased by 30-40%. The serum cholesterol (Chol) concentration was reduced by 33% and the low density lipoprotein (LDL) Chol by 37% in HLP type IIA and IIB. The LDL Chol decreased by 32% in normolipoproteinaemic patients and by 21% in HLP type IV. The mean value for serum cholesterol after therapy was in all groups close to 200 mg/100 ml. In hypertriglyceridaemic patients high density lipoprotein (HDL) Chol increased by 18%. Clofibrate and niceritrol differed with regard to the effect on serum lipoprotein concentrations as well as on other metabolic parameters. Niceritrol was significantly more effective than clofibrate in lowering LDL Chol and in increasing HDL Chol. Niceritrol treatment significantly reduced the Chol/TG ratio in VLDL while no such effect was seen during clofibrate administration. The two drugs also showed significantly different effects on the fractional removal rate (K2) of triglyceride-rich lipoproteins as measured by the intravenous fat tolerance test (IVFTT). The K2 was significantly increased by clofibrate but was not affected by niceritrol treatment. The two drugs differed also with regard to the effects on serum uric acid concentration and the liver function tests. The plasma fibrinogen levels and the erythrocyte sedimentation rates were reduced during treatment with both niceritrol and clofibrate. The present study demonstrates that it is possible to obtain substantial reductions of serum lipoprotein concentrations by combining lipid-lowering diet, clofibrate and niceritrol treatment. There was an additive lipid-lowering effect of this treatment and the combination of the two drugs seemed beneficial in regard to certain possible side effects. The impact of a lipid reduction within this range on cardiovascular morbidity and mortality remains to be evaluated."}
{"id": "PMID:228686", "title": "[Lipid aspects in subjects with glucose-6-phosphate dehydrogenase deficiency].", "content": "To control some aspects of Lipid metabolism in G-6-PD defective subjects, are evaluated the haematic levels of Cholesterol, Tri glycerides, total Lipids and Lipoproteins. There is no significative difference between enzymopathic and normal control subjects.", "contents": "[Lipid aspects in subjects with glucose-6-phosphate dehydrogenase deficiency]. To control some aspects of Lipid metabolism in G-6-PD defective subjects, are evaluated the haematic levels of Cholesterol, Tri glycerides, total Lipids and Lipoproteins. There is no significative difference between enzymopathic and normal control subjects."}
{"id": "PMID:228687", "title": "[Effects of calcium, ethanol and hyperosmolarity on the distribution of intervals between MEPP's].", "content": "Distributions of intervals between MEPP's, recorded from the frog sartorius muscle in various experimental conditions, were compared, graphically and by X2, with the exponential distributions expected for a Poisson process. For each experiment, 200 intervals were measured. In isotonic Ringer solutions containing no Ca++, MEPP's fitted an exponential distribution; by adding Ca++ (1 mM, 2,5 MM, 15 mM), the fit between empirical and expected distributions became poorer, with an excess of short intervals. MEPP's showed the tendency to occur in bursts, and this was particularly evident at 15 mM Ca++. In the presence of 0,5% ethanol, also at high Ca++ the intervals between MEPP's showed a fair fit to the exponential distribution. In Ringer solutions made hypertonic by the addition of 50 mM sucrose, the fit was poor and there was a relative lack of short intervals. These different patterns of MEPP distribution could be explained by supposing that Ca++, ethanol and hypertonicity activate different mechanisms of transmitter release.", "contents": "[Effects of calcium, ethanol and hyperosmolarity on the distribution of intervals between MEPP's]. Distributions of intervals between MEPP's, recorded from the frog sartorius muscle in various experimental conditions, were compared, graphically and by X2, with the exponential distributions expected for a Poisson process. For each experiment, 200 intervals were measured. In isotonic Ringer solutions containing no Ca++, MEPP's fitted an exponential distribution; by adding Ca++ (1 mM, 2,5 MM, 15 mM), the fit between empirical and expected distributions became poorer, with an excess of short intervals. MEPP's showed the tendency to occur in bursts, and this was particularly evident at 15 mM Ca++. In the presence of 0,5% ethanol, also at high Ca++ the intervals between MEPP's showed a fair fit to the exponential distribution. In Ringer solutions made hypertonic by the addition of 50 mM sucrose, the fit was poor and there was a relative lack of short intervals. These different patterns of MEPP distribution could be explained by supposing that Ca++, ethanol and hypertonicity activate different mechanisms of transmitter release."}
{"id": "PMID:228688", "title": "[Glioma in the aged (author's transl)].", "content": "Glioma is the most frequent primary brain tumor in the aged which is originally much less frequent comparing that of younger generations. A large majority of gliomas in the aged is malignant. Besides the result of operation and follow-up result have been heretofore reported as more unfavorable. Fourteen cases of glioma in the aged, over 60 years of age, including 7 glioblastomas, 6 anaplastic astrocytomas and one unspecified malignant glioma, have been reported. Preoperative period varied from one month to 15 years and in 6 cases the period was less than 3 months. Poor preoperative state especially disturbance of consciousness mostly due to a markedly increased intracranial pressure, observed in 71% of the cases. The malignant gliomas which were frequently seen among the aged might be transformed tumors of more benign gliomas which originated in the younger generations and developed slowly and silently. Unfavorable prognosis of glioma in the aged might be closely related to the histological nature and poor preoperative state. However, delay of making correct diagnosis and rapidly progressive onset both of which have been mentioned as the speciality of brain tumor in the aged, were not closely related to the unfavorable prognosis.", "contents": "[Glioma in the aged (author's transl)]. Glioma is the most frequent primary brain tumor in the aged which is originally much less frequent comparing that of younger generations. A large majority of gliomas in the aged is malignant. Besides the result of operation and follow-up result have been heretofore reported as more unfavorable. Fourteen cases of glioma in the aged, over 60 years of age, including 7 glioblastomas, 6 anaplastic astrocytomas and one unspecified malignant glioma, have been reported. Preoperative period varied from one month to 15 years and in 6 cases the period was less than 3 months. Poor preoperative state especially disturbance of consciousness mostly due to a markedly increased intracranial pressure, observed in 71% of the cases. The malignant gliomas which were frequently seen among the aged might be transformed tumors of more benign gliomas which originated in the younger generations and developed slowly and silently. Unfavorable prognosis of glioma in the aged might be closely related to the histological nature and poor preoperative state. However, delay of making correct diagnosis and rapidly progressive onset both of which have been mentioned as the speciality of brain tumor in the aged, were not closely related to the unfavorable prognosis."}
{"id": "PMID:228691", "title": "Evaluation of leucocyte adherence inhibition in hepatocellular carcinoma.", "content": "The value of the leucocyte adherence inhibition (LAI) test in the diagnosis of hepatocellular carcinoma (HCG) was investigated in 36 patients with this tumour. The sensitivity and specificity of the tube LAI test was assessed in 21 patients with HCC, 15 apparently healthy individuals, 9 patients with various forms of benign liver disease and 5 patients with non-hepatic neoplasms. In only 42% of the HCC patients tested was leucocyte adherence to glass reduced to a greater extent than in the healthy controls and in the patients with non-hepatic neoplasms, and the differences were not statistically significant. Moreover, positive results were obtained in 6/9 patients with benign hepatic disease. A further 15 patients were tested against extracts of HCC tissue using the haemacytometer LAI method. Of these, 53% gave positive results. In all, only 17/36 patients (47%) gave positive LAI responses. The test is thus of limited value in the diagnosis of HCC. The high false-negative result rate may be due either to abrogation of the immune response in HCC patients with large tumour burdens or to antigenic heterogeneity in HCC.", "contents": "Evaluation of leucocyte adherence inhibition in hepatocellular carcinoma. The value of the leucocyte adherence inhibition (LAI) test in the diagnosis of hepatocellular carcinoma (HCG) was investigated in 36 patients with this tumour. The sensitivity and specificity of the tube LAI test was assessed in 21 patients with HCC, 15 apparently healthy individuals, 9 patients with various forms of benign liver disease and 5 patients with non-hepatic neoplasms. In only 42% of the HCC patients tested was leucocyte adherence to glass reduced to a greater extent than in the healthy controls and in the patients with non-hepatic neoplasms, and the differences were not statistically significant. Moreover, positive results were obtained in 6/9 patients with benign hepatic disease. A further 15 patients were tested against extracts of HCC tissue using the haemacytometer LAI method. Of these, 53% gave positive results. In all, only 17/36 patients (47%) gave positive LAI responses. The test is thus of limited value in the diagnosis of HCC. The high false-negative result rate may be due either to abrogation of the immune response in HCC patients with large tumour burdens or to antigenic heterogeneity in HCC."}
{"id": "PMID:228692", "title": "The antitumour agent 5-(3,3-dimethyl-1-triazeno) imidazole-4-carboxamide (DTIC) inhibits rat liver cAMP phosphodiesterase and amplifies hormone effects in hepatocytes and hepatoma cells.", "content": "The antitumour agent 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) was found to inhibit competitively the low-Km cyclic AMP phosphodiesterase activity in an ammonium-sulphate-precipitable fraction of the 2,000g supernatant of rat liver. With substrate concentration at 0.25 microM, I50 was 790 microM for DTIC and 350 microM for theophylline. DTIC at 2 mM more than doubled the cAMP response to glucagon in hepatocytes and to adrenaline in MH1C1 hepatoma cells, indicating that it also exerts its inhibitory effect on the phosphodiesterase in intact cells. The possible contribution of the phosphodiesterase inhibition to the growth-inhibitory and cytotoxic effects of DTIC is discussed.", "contents": "The antitumour agent 5-(3,3-dimethyl-1-triazeno) imidazole-4-carboxamide (DTIC) inhibits rat liver cAMP phosphodiesterase and amplifies hormone effects in hepatocytes and hepatoma cells. The antitumour agent 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) was found to inhibit competitively the low-Km cyclic AMP phosphodiesterase activity in an ammonium-sulphate-precipitable fraction of the 2,000g supernatant of rat liver. With substrate concentration at 0.25 microM, I50 was 790 microM for DTIC and 350 microM for theophylline. DTIC at 2 mM more than doubled the cAMP response to glucagon in hepatocytes and to adrenaline in MH1C1 hepatoma cells, indicating that it also exerts its inhibitory effect on the phosphodiesterase in intact cells. The possible contribution of the phosphodiesterase inhibition to the growth-inhibitory and cytotoxic effects of DTIC is discussed."}
{"id": "PMID:228693", "title": "Focal epithelial hyperplasia of the oral mucosa. A case report from the United Kingdom.", "content": "A case of focal epithelial hyperplasia of the oral mucosa (Heck's disease) is presented, which appears to be the first to be described in the United Kingdom. Virus particles were found in tissue from the lesions studied by electron microscopy, and identified as belonging to the papilloma virus sub-group of the family of papovaviruses.", "contents": "Focal epithelial hyperplasia of the oral mucosa. A case report from the United Kingdom. A case of focal epithelial hyperplasia of the oral mucosa (Heck's disease) is presented, which appears to be the first to be described in the United Kingdom. Virus particles were found in tissue from the lesions studied by electron microscopy, and identified as belonging to the papilloma virus sub-group of the family of papovaviruses."}
{"id": "PMID:228694", "title": "Studies on the plasma membrane of normal and psoriatic keratinocytes. 2. Cyclic AMP and its response to hormonal stimulation.", "content": "Cyclic AMP levels have been determined for the first time in isolated keratinocytes. Values were more reproducible than those reported using epidermal slices. Evidence is presented to show that damage to hormone receptors is minimal. Other observations include the following: (1) Keratinocytes from psoriatic lesions showed reduced 'resting' levels of cyclic AMP as well as a diminished response to adrenaline. (2) Cyclic AMP levels were maximal in the basal cells, falling dramatically in fully differentiated keratinocytes. (3) The topical application of a corticosteroid (fluocinolone acetonide) did not modulate the response of adenyl cyclase to hormonal stimulation.", "contents": "Studies on the plasma membrane of normal and psoriatic keratinocytes. 2. Cyclic AMP and its response to hormonal stimulation. Cyclic AMP levels have been determined for the first time in isolated keratinocytes. Values were more reproducible than those reported using epidermal slices. Evidence is presented to show that damage to hormone receptors is minimal. Other observations include the following: (1) Keratinocytes from psoriatic lesions showed reduced 'resting' levels of cyclic AMP as well as a diminished response to adrenaline. (2) Cyclic AMP levels were maximal in the basal cells, falling dramatically in fully differentiated keratinocytes. (3) The topical application of a corticosteroid (fluocinolone acetonide) did not modulate the response of adenyl cyclase to hormonal stimulation."}
{"id": "PMID:228695", "title": "Hand grip forces during chain saw operation and vibration white finger in lumberjacks.", "content": "The hand grip forces at the front and rear handles of a chain saw were measured during work, in 89 professional lumberjacks. The symptoms caused by vibration to the upper limbs were compared with the hand grip force (HGF) during work. To allow better comparison between subjects we used the ratio of hand grip force (HGF) to the maximal voluntary compression force (MVC), HGF/MVC expressed as a percentage. The mean HGF during sawing varied from 5 to 12 N in all subjects. The variation in HGF was greater at the front handle than at the rear handle, during sawing. The lumberjacks who had vibration-induced white fingers (VWF), had a higher HGF/MVC in both hands than the lumberjacks without VWF. Those lumberjacks affected by VWF used over 12% of their MVC at work. Subjects without HGF/MVC ratio. The lumberjacks with and without numbness in their hands had equal HGF/MVC ratios.", "contents": "Hand grip forces during chain saw operation and vibration white finger in lumberjacks. The hand grip forces at the front and rear handles of a chain saw were measured during work, in 89 professional lumberjacks. The symptoms caused by vibration to the upper limbs were compared with the hand grip force (HGF) during work. To allow better comparison between subjects we used the ratio of hand grip force (HGF) to the maximal voluntary compression force (MVC), HGF/MVC expressed as a percentage. The mean HGF during sawing varied from 5 to 12 N in all subjects. The variation in HGF was greater at the front handle than at the rear handle, during sawing. The lumberjacks who had vibration-induced white fingers (VWF), had a higher HGF/MVC in both hands than the lumberjacks without VWF. Those lumberjacks affected by VWF used over 12% of their MVC at work. Subjects without HGF/MVC ratio. The lumberjacks with and without numbness in their hands had equal HGF/MVC ratios."}
{"id": "PMID:228696", "title": "An analysis of the influences of maternal age, gestational age, contraceptive method, and the mode of primary treatment of patients with hydatidiform moles on the incidence of subsequent chemotherapy.", "content": "In relation to the total number of births in the United Kingdom there was an excess of hydatidiform moles arising in women over 34 years of age and possibly also under 15. The incidence of trophoblastic tumour requiring chemotherapy after hydatidiform mole was greatest in the 30 to 34 years age group and it was also high in the 20 to 24 years age group. This distribution appears to be influenced by the morphology of the moles, the mode of their removal and the use of oestrogens and progestogens in the post-evacuation period. The need for chemotherapy for trophoblastic tumour after evacuation of a hydatidiform mole was found to be two- to three-fold greater in patients who had undergone a medical induction, hysterectomy or hysterotomy compared with those whose hydatidiform moles had been evacuated by vacuum or surgical curettage, or who had aborted spontaneously. The increased risk of chemotherapy was most marked in the earlier weeks of gestation.", "contents": "An analysis of the influences of maternal age, gestational age, contraceptive method, and the mode of primary treatment of patients with hydatidiform moles on the incidence of subsequent chemotherapy. In relation to the total number of births in the United Kingdom there was an excess of hydatidiform moles arising in women over 34 years of age and possibly also under 15. The incidence of trophoblastic tumour requiring chemotherapy after hydatidiform mole was greatest in the 30 to 34 years age group and it was also high in the 20 to 24 years age group. This distribution appears to be influenced by the morphology of the moles, the mode of their removal and the use of oestrogens and progestogens in the post-evacuation period. The need for chemotherapy for trophoblastic tumour after evacuation of a hydatidiform mole was found to be two- to three-fold greater in patients who had undergone a medical induction, hysterectomy or hysterotomy compared with those whose hydatidiform moles had been evacuated by vacuum or surgical curettage, or who had aborted spontaneously. The increased risk of chemotherapy was most marked in the earlier weeks of gestation."}
{"id": "PMID:228697", "title": "Selective deficiency of hepatic triglyceride lipase and hypertriglyceridaemia in kwashiorkor.", "content": "1. Serum postheparin lipolytic activities (PHLA), triglyceride and free fatty acid concentrations were determined in children with kwashiorkor before and after treatment and also in normal control children. 2. Using the range (571-1650 mumol/l) of serum triglyceride of the control children as normal, five (20%) of the twenty-five children with kwashiorkor had low (less than 570 mumol/l), thirteen (52%) had normal (571-1650 mumol/l) and seven (28%) had high (more than 1650 mumol/l) serum triglyceride levels. 3. The serum PHLA did not show any definite correlation with the level of circulating triglycerides, although the lowest levels of PHLA were found in the malnourished children with highest triglyceride level. 4. While the hepatic PHLA in the malnourished children was significantly less than control value, the extrahepatic PHLA did not differ significantly. 5. After treatment, serum PHLA rose significantly and the mean levels were within normal range. 6. Our findings suggest that a defect in catabolism of very-low-density lipoprotein caused by a low hepatic PHLA may cause hypertriglyceridaemia in children with kwashiorkor.", "contents": "Selective deficiency of hepatic triglyceride lipase and hypertriglyceridaemia in kwashiorkor. 1. Serum postheparin lipolytic activities (PHLA), triglyceride and free fatty acid concentrations were determined in children with kwashiorkor before and after treatment and also in normal control children. 2. Using the range (571-1650 mumol/l) of serum triglyceride of the control children as normal, five (20%) of the twenty-five children with kwashiorkor had low (less than 570 mumol/l), thirteen (52%) had normal (571-1650 mumol/l) and seven (28%) had high (more than 1650 mumol/l) serum triglyceride levels. 3. The serum PHLA did not show any definite correlation with the level of circulating triglycerides, although the lowest levels of PHLA were found in the malnourished children with highest triglyceride level. 4. While the hepatic PHLA in the malnourished children was significantly less than control value, the extrahepatic PHLA did not differ significantly. 5. After treatment, serum PHLA rose significantly and the mean levels were within normal range. 6. Our findings suggest that a defect in catabolism of very-low-density lipoprotein caused by a low hepatic PHLA may cause hypertriglyceridaemia in children with kwashiorkor."}
{"id": "PMID:228698", "title": "25-Hydroxyvitamin D3 26,23-lactone: a new in vivo metabolite of vitamin D.", "content": "A major vitamin D metabolite was isolated in pure form from the blood plasma of chicks either maintenance levels or large doses of vitamin D3. The isolation involved methanol-chloroform extraction and five column chromatographic procedures. The metabolite purification and elution position on these columns were followed by a competitive protein binding assay. The metabolite was identified, using high- and low-resolution mass spectrometry, 270-MHz proton nuclear magnetic resonance spectrometry, ultraviolet absorption spectrophotometry, Fourier transform infrared spectrophotometry, and specific chemical reactions, as 3 beta,-25-dihydroxy-9,10-seco-5,7,10(19)-cholestatrieno-26,23-lactone. The trivial names 25-hydroxyvitamin D3 26,23-lactone or calcidiol 26,23-lactone are suggested for this compound.", "contents": "25-Hydroxyvitamin D3 26,23-lactone: a new in vivo metabolite of vitamin D. A major vitamin D metabolite was isolated in pure form from the blood plasma of chicks either maintenance levels or large doses of vitamin D3. The isolation involved methanol-chloroform extraction and five column chromatographic procedures. The metabolite purification and elution position on these columns were followed by a competitive protein binding assay. The metabolite was identified, using high- and low-resolution mass spectrometry, 270-MHz proton nuclear magnetic resonance spectrometry, ultraviolet absorption spectrophotometry, Fourier transform infrared spectrophotometry, and specific chemical reactions, as 3 beta,-25-dihydroxy-9,10-seco-5,7,10(19)-cholestatrieno-26,23-lactone. The trivial names 25-hydroxyvitamin D3 26,23-lactone or calcidiol 26,23-lactone are suggested for this compound."}
{"id": "PMID:228699", "title": "Enzymatic properties of 8-bromoadenine nucleotides.", "content": "8-Bromoadenine nucleotides were tested as potential substrates and/or inhibitors of mitochondrial processes in intact or disrupted organelles, as substrates of various phosphotransferases, and as allosteric effectors in the reactions catalyzed by phosphofructokinase, isocitrate dehydrogenase, glutamate dehydrogenase, and fructose-1,6-bisphosphatase. 8-BrATP and 8-BrADP are not recognized by the translocase system located in the inner mitochondrial membrane and cannot be used as usbstrates in oxidative phosphorylation and related reactions catalyzed be beef heart submitochondrial membranes. This confirms the high specificity for adenine nucleotides of the mammalian systems involved in energy-yielding and energy-requiring reactions. However, 8-BrATP and 8-BrADP are able to substitute for the natural adenine nucleotides in reactions catalyzed by many phosphotransferases, although their capacity as phosphate donors and acceptors is generally much reduced. On the other hand, in almost all investigated cases, the 8-bromoadenine nucleotides have lost the capability of the natural adenine nucleotides to act as allosteric effectors, indicating that the structural requirements for allosteric activity are more stringent than those for catalytic activity.", "contents": "Enzymatic properties of 8-bromoadenine nucleotides. 8-Bromoadenine nucleotides were tested as potential substrates and/or inhibitors of mitochondrial processes in intact or disrupted organelles, as substrates of various phosphotransferases, and as allosteric effectors in the reactions catalyzed by phosphofructokinase, isocitrate dehydrogenase, glutamate dehydrogenase, and fructose-1,6-bisphosphatase. 8-BrATP and 8-BrADP are not recognized by the translocase system located in the inner mitochondrial membrane and cannot be used as usbstrates in oxidative phosphorylation and related reactions catalyzed be beef heart submitochondrial membranes. This confirms the high specificity for adenine nucleotides of the mammalian systems involved in energy-yielding and energy-requiring reactions. However, 8-BrATP and 8-BrADP are able to substitute for the natural adenine nucleotides in reactions catalyzed by many phosphotransferases, although their capacity as phosphate donors and acceptors is generally much reduced. On the other hand, in almost all investigated cases, the 8-bromoadenine nucleotides have lost the capability of the natural adenine nucleotides to act as allosteric effectors, indicating that the structural requirements for allosteric activity are more stringent than those for catalytic activity."}
{"id": "PMID:228700", "title": "Possibility of shape conformers of the protein inhibitor of the cyclic adenosine monophosphate dependent protein kinase.", "content": "The heat-stable, protein inhibitor of the cyclic adenosine monophosphate (cAMP) dependent protein kinase [Walsh, D. A., Ashby, C. D., Gonzalez, C., Calkins, D., Fischer, E., & Krebs, E (1971a) J. Biol. Chem. 246, 1977-1985] has been purified to homogeneity from rabbit skeletal muscle by preparative electrophoresis. Employing a more sensitive assay system, we detected multiple charged forms of the inhibitor on diethylaminoethyl chromatography; the form that has been further characterized is the predominant species in skeletal muscle comprising greater than 70% of the total. The apparent molecular weight of the protein inhibitor, as determined by Sephadex G-75 gel exclusion chromatography, is 22 000 in initial cellular extracts and at all stages during the purification prior to the final purification step of preparative gel electrophoresis, after which the homogeneous protein exhibits a molecular weight of 11 000. These two forms are designated I and I', respectively. The I form migrates with an apparent molecular weight of 10 000 on nondenaturing gel electrophoresis and of 10 500-11 500 on sodium dodecyl sulfate (NaDodSO4) gel electrophoresis; the I' form migrates with an apparent molecular weight of 6500-8300 on NaDodSO4 electrophoresis and has a minimum molecular weight of 10 400 by amino acid analysis. Taking into account the anomalous behavior displayed by low molecular weight proteins with the various techniques employed, we suggest that the I and I' forms of the protein inhibitor may represent shape conformers.", "contents": "Possibility of shape conformers of the protein inhibitor of the cyclic adenosine monophosphate dependent protein kinase. The heat-stable, protein inhibitor of the cyclic adenosine monophosphate (cAMP) dependent protein kinase [Walsh, D. A., Ashby, C. D., Gonzalez, C., Calkins, D., Fischer, E., & Krebs, E (1971a) J. Biol. Chem. 246, 1977-1985] has been purified to homogeneity from rabbit skeletal muscle by preparative electrophoresis. Employing a more sensitive assay system, we detected multiple charged forms of the inhibitor on diethylaminoethyl chromatography; the form that has been further characterized is the predominant species in skeletal muscle comprising greater than 70% of the total. The apparent molecular weight of the protein inhibitor, as determined by Sephadex G-75 gel exclusion chromatography, is 22 000 in initial cellular extracts and at all stages during the purification prior to the final purification step of preparative gel electrophoresis, after which the homogeneous protein exhibits a molecular weight of 11 000. These two forms are designated I and I', respectively. The I form migrates with an apparent molecular weight of 10 000 on nondenaturing gel electrophoresis and of 10 500-11 500 on sodium dodecyl sulfate (NaDodSO4) gel electrophoresis; the I' form migrates with an apparent molecular weight of 6500-8300 on NaDodSO4 electrophoresis and has a minimum molecular weight of 10 400 by amino acid analysis. Taking into account the anomalous behavior displayed by low molecular weight proteins with the various techniques employed, we suggest that the I and I' forms of the protein inhibitor may represent shape conformers."}
{"id": "PMID:228701", "title": "Iron-sulfur clusters in the molybdenum-iron protein component of nitrogenase. Electron paramagnetic resonance of the carbon monoxide inhibited state.", "content": "Carbon monoxide inhibits reduction of dinitrogen (N2) by purified nitrogenase from Azotobacter vinelandii and Clostridium pasteurianum in a noncompetitive manner (Kii and Kis = 1.4 X 10(-4) and 4.5 X 10(-4) and 7 X 10(-4) atm and 14 X 10(-4) atm for the two enzymes, respectively). The onset of inhibition is within the turnover time of the enzyme, and CO does not affect the electron flux to the H2-evolving site. The kinetics of CO inhibition of N2 reduction are simple, but CO inhibition of acetylene reduction is complicated by substrate inhibition effects. When low-temperature (approximately 13 K) electron paramagnetic resonance (EPR) spectra of CO-inhibited nitrogenase are examined, it is found that low concentrations of CO ([CO] = [enzyme]) induce the appearance of a signal with g values near 2.1, 1.98, and 1.92 with t1/2 approximately 4 s, while higher concentrations of CO lead to the appearance of a signal with g values near 2.17, 2.1, and 2.05 with a similar time course. The MoFe proteins from Rhizobium japonicum and Rhodospirillum rubrum, reduced with Azotobacter Fe protein in the presence of CO, give similar results. Under conditions which promote the accumulation of H2 in the absence of CO, an additional EPR signal with g values near 2.1, 2.0, and 1.98 is observed. The use of Azotobacter nitogenase components enriched selectively with 57Fe or 95Mo, as well as the use of 13CO, permitted the assignment of the center(s) responsible for the induced signals. Only 57Fe, when present in the MoFe protein, yielded broadened EPR signals. It is suggested that the MoFe protein of nitrogenase contains one or more iron-sulfur clusters of the type found in the simple ferrodoxins. It is further proposed that the CO-induced signals arise from states of the MoFe protein in which CO inhibits electron flow to the N2-reducing site so that the iron-sulfur cluster achieves steady-state net charges of -1 (high CO complex) and -3 (low CO complex) in analogy to the normal paramagnetic states of high-potential iron-sulfur proteins and ferredoxins, respectively. The \"no-CO\" signal may be either an additional center or the N2-reducing site with H2 bound competitively.", "contents": "Iron-sulfur clusters in the molybdenum-iron protein component of nitrogenase. Electron paramagnetic resonance of the carbon monoxide inhibited state. Carbon monoxide inhibits reduction of dinitrogen (N2) by purified nitrogenase from Azotobacter vinelandii and Clostridium pasteurianum in a noncompetitive manner (Kii and Kis = 1.4 X 10(-4) and 4.5 X 10(-4) and 7 X 10(-4) atm and 14 X 10(-4) atm for the two enzymes, respectively). The onset of inhibition is within the turnover time of the enzyme, and CO does not affect the electron flux to the H2-evolving site. The kinetics of CO inhibition of N2 reduction are simple, but CO inhibition of acetylene reduction is complicated by substrate inhibition effects. When low-temperature (approximately 13 K) electron paramagnetic resonance (EPR) spectra of CO-inhibited nitrogenase are examined, it is found that low concentrations of CO ([CO] = [enzyme]) induce the appearance of a signal with g values near 2.1, 1.98, and 1.92 with t1/2 approximately 4 s, while higher concentrations of CO lead to the appearance of a signal with g values near 2.17, 2.1, and 2.05 with a similar time course. The MoFe proteins from Rhizobium japonicum and Rhodospirillum rubrum, reduced with Azotobacter Fe protein in the presence of CO, give similar results. Under conditions which promote the accumulation of H2 in the absence of CO, an additional EPR signal with g values near 2.1, 2.0, and 1.98 is observed. The use of Azotobacter nitogenase components enriched selectively with 57Fe or 95Mo, as well as the use of 13CO, permitted the assignment of the center(s) responsible for the induced signals. Only 57Fe, when present in the MoFe protein, yielded broadened EPR signals. It is suggested that the MoFe protein of nitrogenase contains one or more iron-sulfur clusters of the type found in the simple ferrodoxins. It is further proposed that the CO-induced signals arise from states of the MoFe protein in which CO inhibits electron flow to the N2-reducing site so that the iron-sulfur cluster achieves steady-state net charges of -1 (high CO complex) and -3 (low CO complex) in analogy to the normal paramagnetic states of high-potential iron-sulfur proteins and ferredoxins, respectively. The \"no-CO\" signal may be either an additional center or the N2-reducing site with H2 bound competitively."}
{"id": "PMID:228703", "title": "Lithium-7 nuclear magnetic resonance, water proton nuclear magnetic resonance, and gadolinium electron paramagnetic resonance studies of the sarcoplasmic reticulum calcium ion transport adenosine triphosphatase.", "content": "The interactions of gadolinium ion, lithium, and two substrate analogues, beta,gamma-imido-ATP (AMP-PNP) and tridentate CrATP, with the calcium ion transport adenosine triphosphatase (Ca2+-ATPase) of rabbit muscle sarcoplasmic reticulum have been examined by using 7Li+ NMR, water proton NMR, and Gd3+ EPR studies. Steady-state phosphorylation studies indicate that Gd3+ binds to the Ca2+ activator sites on the enzyme with an affinity which is approximately 10 times greater than that of Ca2+. 7Li+, which activates the Ca2+-ATPase in place of K+, has been found to be a suitable nucleus for probing the active sites of monovalent cation-requiring enzymes. 7Li+ nuclear relaxation studies demonstrate that the binding of Gd3+ ion to the two Ca2+ sites on Ca2+-ATPase increases the longitudinal relaxation rate (1/T1) of enzyme-bound Li+. The increase in 1/T1 was not observed in the absence of enzyme, indicating that the ATPase enhances the parmagnetic effect of Gd3+ on 1/T1 of 7Li+. Water proton relaxation studies also show that the ATPase binds Gd3+ at two tight-binding sites. Titrations of Gd3+ solutions with Ca2+-ATPase indicate that the tighter of the two Gd3+-binding sites (site 1) provides a ghigher enhancement of water relaxation than the other, weaker Gd3+ site (site 2) and also indicate that the average of the enhancements at the two sites is 7.4. These data, together with a titration of the ATPase with Gd3+ ion, yield enhancements, epsilonB, of 9.4 at site 1 and 5.4 at site 2. Analysis of the frequency dependence of 1/T1 of water indicates that the electron spin relaxation taus of Gd3+ is unusually long (2 X 10(-9) s) and suggests that the Ca2+-binding sites on the ATPase experience a reduced accessiblity of solvent water. This may indicate that the Ca2+ sites on the Ca2+-ATPase are buried or occluded within a cleft or channel in the enzyme. The analysis of the frequency dependence is also consistent with three exchangeable water protons on Gd3+ at site 1 and two fast exchanging water protons at site 2. Addition of the nonhydrolyzing substrate analogues, AMP-PNP and tridenate CrATP, to the enzyme-Gd3+ complex results in a decrease in the observed enhancement, with little change in the dipolar correlation time for Gd3+, consistent with a substrate-induced decrease in the number of fast-exchanging water protons on enzyme-bound Gd3+. From the effect of Gd3+ on 1/T1 of enzyme-bound Li+, Gd3+-Li+ separations of 7.0 and 9.1 A are calculated. On the assumption of a single Li+ site on the enzyme, these distances set an upper limit on the separation between Ca2+ sites on the enzyme of 16.1 A.", "contents": "Lithium-7 nuclear magnetic resonance, water proton nuclear magnetic resonance, and gadolinium electron paramagnetic resonance studies of the sarcoplasmic reticulum calcium ion transport adenosine triphosphatase. The interactions of gadolinium ion, lithium, and two substrate analogues, beta,gamma-imido-ATP (AMP-PNP) and tridentate CrATP, with the calcium ion transport adenosine triphosphatase (Ca2+-ATPase) of rabbit muscle sarcoplasmic reticulum have been examined by using 7Li+ NMR, water proton NMR, and Gd3+ EPR studies. Steady-state phosphorylation studies indicate that Gd3+ binds to the Ca2+ activator sites on the enzyme with an affinity which is approximately 10 times greater than that of Ca2+. 7Li+, which activates the Ca2+-ATPase in place of K+, has been found to be a suitable nucleus for probing the active sites of monovalent cation-requiring enzymes. 7Li+ nuclear relaxation studies demonstrate that the binding of Gd3+ ion to the two Ca2+ sites on Ca2+-ATPase increases the longitudinal relaxation rate (1/T1) of enzyme-bound Li+. The increase in 1/T1 was not observed in the absence of enzyme, indicating that the ATPase enhances the parmagnetic effect of Gd3+ on 1/T1 of 7Li+. Water proton relaxation studies also show that the ATPase binds Gd3+ at two tight-binding sites. Titrations of Gd3+ solutions with Ca2+-ATPase indicate that the tighter of the two Gd3+-binding sites (site 1) provides a ghigher enhancement of water relaxation than the other, weaker Gd3+ site (site 2) and also indicate that the average of the enhancements at the two sites is 7.4. These data, together with a titration of the ATPase with Gd3+ ion, yield enhancements, epsilonB, of 9.4 at site 1 and 5.4 at site 2. Analysis of the frequency dependence of 1/T1 of water indicates that the electron spin relaxation taus of Gd3+ is unusually long (2 X 10(-9) s) and suggests that the Ca2+-binding sites on the ATPase experience a reduced accessiblity of solvent water. This may indicate that the Ca2+ sites on the Ca2+-ATPase are buried or occluded within a cleft or channel in the enzyme. The analysis of the frequency dependence is also consistent with three exchangeable water protons on Gd3+ at site 1 and two fast exchanging water protons at site 2. Addition of the nonhydrolyzing substrate analogues, AMP-PNP and tridenate CrATP, to the enzyme-Gd3+ complex results in a decrease in the observed enhancement, with little change in the dipolar correlation time for Gd3+, consistent with a substrate-induced decrease in the number of fast-exchanging water protons on enzyme-bound Gd3+. From the effect of Gd3+ on 1/T1 of enzyme-bound Li+, Gd3+-Li+ separations of 7.0 and 9.1 A are calculated. On the assumption of a single Li+ site on the enzyme, these distances set an upper limit on the separation between Ca2+ sites on the enzyme of 16.1 A."}
{"id": "PMID:228705", "title": "Structural comparisons of heme binding proteins.", "content": "Of the 82 three dimensionally characterized residues of cytochrome c551, 49 are found to be structurally and topologically equivalent to the globin fold and 41 are equivalent to the cytochrome b5 fold, with a respective root mean square separation of 3.5 and 4.9 A between equivalenced Calpha atoms. The common fold represents a central heme binding core, corresponding to the middle exon of certain globin genes. After superposition of the protein folds, the heme irons are found to be separated by 5.4 and 1.6 A, while their heme normals are inclined by 6 degrees and 32 degrees, respectively. Furthermore, the heme \"face\", determined by the asymmetric attachment of the vinyl and propionyl side chains, is directed similarly in all three heme proteins. The heme itself is rotated by 72 degrees and 116 degrees about its normal, respectively. The minimum base change per codon for the three pairwise comparisons corresponds to the expected value of random sequence comparisons. While all three heme proteins may have diverged from a common ancestor, their similarity may have arisen from the requirements of heme binding or the utilization of a particularly stable fold. Known structures within commonly accepted divergent families were superimposed in order to discriminate better between convergence and divergence. Minimum base changes per codon, number of deletions and insertions, percentage of equivalenced residues, precision of heme superposition, and root mean square separation of equivalenced Calpha atoms were tested as measures of evolutionary relationships.", "contents": "Structural comparisons of heme binding proteins. Of the 82 three dimensionally characterized residues of cytochrome c551, 49 are found to be structurally and topologically equivalent to the globin fold and 41 are equivalent to the cytochrome b5 fold, with a respective root mean square separation of 3.5 and 4.9 A between equivalenced Calpha atoms. The common fold represents a central heme binding core, corresponding to the middle exon of certain globin genes. After superposition of the protein folds, the heme irons are found to be separated by 5.4 and 1.6 A, while their heme normals are inclined by 6 degrees and 32 degrees, respectively. Furthermore, the heme \"face\", determined by the asymmetric attachment of the vinyl and propionyl side chains, is directed similarly in all three heme proteins. The heme itself is rotated by 72 degrees and 116 degrees about its normal, respectively. The minimum base change per codon for the three pairwise comparisons corresponds to the expected value of random sequence comparisons. While all three heme proteins may have diverged from a common ancestor, their similarity may have arisen from the requirements of heme binding or the utilization of a particularly stable fold. Known structures within commonly accepted divergent families were superimposed in order to discriminate better between convergence and divergence. Minimum base changes per codon, number of deletions and insertions, percentage of equivalenced residues, precision of heme superposition, and root mean square separation of equivalenced Calpha atoms were tested as measures of evolutionary relationships."}
{"id": "PMID:228707", "title": "The respiratory chain of Paramecium tetraurelia in wild type and the mutant Cl1. I. Spectral properties and redox potentials.", "content": "1. Purified mitochondria have been prepared from wild type Paramecium tetraurelia and from the mutant Cl1 which lacks cytochrome aa3. Both mitochondrial preparations are characterized by cyanide insensitivity. Their spectral properties and their redox potentials have been studied. 2. Difference spectra (dithionite reduced minus oxidized) of mitochondria from wild type P. tetraurelia at 77 K revealed the alpha peaks of b-type cytochrome (s) at 553 and 557 nm, of c-type cytochrome at 549 nm and a-type cytochrome at 608 nm. Two alpha peaks at 549 and 545 nm could be distinguished in the isolated cytochrome c at 77 K. After cytochrome c extraction from wild type mitochondria, a new peak at 551 nm was unmasked, probably belonging to cytochdrome c1. The a-type cytochrome was characterized by a split Soret band with maxima at 441 and 450 nm. The mitochondria of the mutant Cl1 in exponential phase of growth differed from the wild type mitochondria in that cytochrome aa3 was absent while twice the quantity of cytochrome b was present. In stationary phase, mitochondria of the mutant were characterized by a new absorption peak at 590 nm. 3. Cytochrome aa3 was present at a concentration of 0.3 nmol/mg protein in wild type mitochondria and ubiquinone at a concentration of 8 nmol/mg protein both in mitochondria of the wild type and the mutant Cl1. Cytochrome aa3 was more susceptible to heat than cytochromes b and c,c1.", "contents": "The respiratory chain of Paramecium tetraurelia in wild type and the mutant Cl1. I. Spectral properties and redox potentials. 1. Purified mitochondria have been prepared from wild type Paramecium tetraurelia and from the mutant Cl1 which lacks cytochrome aa3. Both mitochondrial preparations are characterized by cyanide insensitivity. Their spectral properties and their redox potentials have been studied. 2. Difference spectra (dithionite reduced minus oxidized) of mitochondria from wild type P. tetraurelia at 77 K revealed the alpha peaks of b-type cytochrome (s) at 553 and 557 nm, of c-type cytochrome at 549 nm and a-type cytochrome at 608 nm. Two alpha peaks at 549 and 545 nm could be distinguished in the isolated cytochrome c at 77 K. After cytochrome c extraction from wild type mitochondria, a new peak at 551 nm was unmasked, probably belonging to cytochdrome c1. The a-type cytochrome was characterized by a split Soret band with maxima at 441 and 450 nm. The mitochondria of the mutant Cl1 in exponential phase of growth differed from the wild type mitochondria in that cytochrome aa3 was absent while twice the quantity of cytochrome b was present. In stationary phase, mitochondria of the mutant were characterized by a new absorption peak at 590 nm. 3. Cytochrome aa3 was present at a concentration of 0.3 nmol/mg protein in wild type mitochondria and ubiquinone at a concentration of 8 nmol/mg protein both in mitochondria of the wild type and the mutant Cl1. Cytochrome aa3 was more susceptible to heat than cytochromes b and c,c1."}
{"id": "PMID:228708", "title": "EPR spectra of photosystem I and other iron protein components in intact cells of cyanobacteria.", "content": "Electron paramagnetic resonance (EPR) spectra were recorded of whole filaments of the cyanobacteria Nostoc muscorum and Anabaena cylindrica. Signals due to manganese were removed by freezing and thawing the cells in EDTA. EPR spectra were assigned on the basis of their g values, linewidths, temperature dependence and response to dithionite and light treatments. The principal components identified were: (i) rhombic Fe3+ (signal at g = 4.3), probably a soluble storage form of iron; (ii) iron-sulfur centers A and B of Photosystem I; (iii) the photochemical electron acceptor 'X' of Photosystem I; this component was also observed for the first time in isolated heterocysts; (iv) soluble ferredoxin which was present at a concentration of 1 molecule per 140 +/- 20 chlorophyll molecules; (v) a membrane-bound iron-sulfur protein (g = 1.92). A signal g = 6 in the oxidized state was probably due to an unidentified heme compound. During deprivation of iron the rhombic Fe3+, centers A, B and X of Photosystem I, and soluble ferredoxin were all observed to decrease.", "contents": "EPR spectra of photosystem I and other iron protein components in intact cells of cyanobacteria. Electron paramagnetic resonance (EPR) spectra were recorded of whole filaments of the cyanobacteria Nostoc muscorum and Anabaena cylindrica. Signals due to manganese were removed by freezing and thawing the cells in EDTA. EPR spectra were assigned on the basis of their g values, linewidths, temperature dependence and response to dithionite and light treatments. The principal components identified were: (i) rhombic Fe3+ (signal at g = 4.3), probably a soluble storage form of iron; (ii) iron-sulfur centers A and B of Photosystem I; (iii) the photochemical electron acceptor 'X' of Photosystem I; this component was also observed for the first time in isolated heterocysts; (iv) soluble ferredoxin which was present at a concentration of 1 molecule per 140 +/- 20 chlorophyll molecules; (v) a membrane-bound iron-sulfur protein (g = 1.92). A signal g = 6 in the oxidized state was probably due to an unidentified heme compound. During deprivation of iron the rhombic Fe3+, centers A, B and X of Photosystem I, and soluble ferredoxin were all observed to decrease."}
{"id": "PMID:228709", "title": "Orientation of the bacteriochlorophyll triplet and the primary ubiquinone acceptor of Rhodospirillum rubrum in membrane multilayers determined by ESR spectroscopy (I).", "content": "Chromatophores from Rhodospirillum rubrum were oriented as multilayers on quartz slides under reducing conditions. Irradiation of these multilayers in the resonance cavity of an ESR spectrometer at 6 K yielded the spectrum of the bacteriochlorophyll dimer triplet. The relative intesities of the main six lines of the triplet were dependent on the angle subtended by the direction of the external magnetic field with plane of the multilayers. The angular dependence of the intensities of these transitions can best be interpreted in terms of one of the principal axes of the triplet lying along the plane of the membrane while the other two axes are titled 10--20 degrees away from the parallel to and normal to the membrane directions. If we assume the porphyrin planes of the dimer to be parallel and the largest splitting of the triplet transitions to correspond to those transitions in a direction normal to this plane, then these data imply that the dimer planes are nearly perpendicular to the membrane plane. Purified iron-depleted phototrap complexes were similarly oriented in reconstituted phosphatidylcholine multilayers and the angular dependence of the light-induced spectrum recorded at room temperature. A computer analysis of this angular dependence suggests that the plane of the primary ubiquinone acceptor molecule is parallel to the plane of the membrane and therefore perpendicular to the donor.", "contents": "Orientation of the bacteriochlorophyll triplet and the primary ubiquinone acceptor of Rhodospirillum rubrum in membrane multilayers determined by ESR spectroscopy (I). Chromatophores from Rhodospirillum rubrum were oriented as multilayers on quartz slides under reducing conditions. Irradiation of these multilayers in the resonance cavity of an ESR spectrometer at 6 K yielded the spectrum of the bacteriochlorophyll dimer triplet. The relative intesities of the main six lines of the triplet were dependent on the angle subtended by the direction of the external magnetic field with plane of the multilayers. The angular dependence of the intensities of these transitions can best be interpreted in terms of one of the principal axes of the triplet lying along the plane of the membrane while the other two axes are titled 10--20 degrees away from the parallel to and normal to the membrane directions. If we assume the porphyrin planes of the dimer to be parallel and the largest splitting of the triplet transitions to correspond to those transitions in a direction normal to this plane, then these data imply that the dimer planes are nearly perpendicular to the membrane plane. Purified iron-depleted phototrap complexes were similarly oriented in reconstituted phosphatidylcholine multilayers and the angular dependence of the light-induced spectrum recorded at room temperature. A computer analysis of this angular dependence suggests that the plane of the primary ubiquinone acceptor molecule is parallel to the plane of the membrane and therefore perpendicular to the donor."}
{"id": "PMID:228710", "title": "The oxygen reactions of reduced cytochrome c oxidase. Position of a form with an unusual EPR signal in the sequence of early intermediates.", "content": "The order of appearance of intermediates in the reoxidation of reduced cytochrome c oxidase by oxygen has been examined. Particular emphasis was placed on determining where the intermediate with the EPR signal at g = 5, 1.78, 1.69 (Shaw, R.W., Hansen, R.E. and Beinert, H. (1978) J. Biol. Chem. 253, 6637--6640) appears in the sequence of events during reoxidation. Flash photolysis of reduced, CO-complexed samples of cytochrome c oxidase in the presence of oxygen in a buffer containing 30% (v/v) ethylene glycol at 77 K and 195 K has been used to generate states of partial reoxidation. The intermediate with the EPR signal at g = 5, 1.78, and 1.69 can be detected as a product of the photolysis and subsequent oxidation but does not appear until the photolyzed sample is incubated at temperatures well above 196 K. In the course of the reoxidation, the intermediate characterized by the g = 5, 1.78, 1.69 signal occurs in the reaction sequence after the states referred to as 'Compound A' and 'Compound B' (Chance, B., Saronio, C., and Leigh, J.S. (1975) J. Biol. Chem. 250, 9226--9237). Its appearance is within the time range reported for the formation of 'oxygenated' cytochrome c oxidase (Orii, Y. (1979) in Cytochrome Oxidase (King, T.E., Orii, Y., Chance, B. and Okunuki, K., eds.), pp. 331--340, Elsevier/North-Holland Biomedical Press, Amsterdam).", "contents": "The oxygen reactions of reduced cytochrome c oxidase. Position of a form with an unusual EPR signal in the sequence of early intermediates. The order of appearance of intermediates in the reoxidation of reduced cytochrome c oxidase by oxygen has been examined. Particular emphasis was placed on determining where the intermediate with the EPR signal at g = 5, 1.78, 1.69 (Shaw, R.W., Hansen, R.E. and Beinert, H. (1978) J. Biol. Chem. 253, 6637--6640) appears in the sequence of events during reoxidation. Flash photolysis of reduced, CO-complexed samples of cytochrome c oxidase in the presence of oxygen in a buffer containing 30% (v/v) ethylene glycol at 77 K and 195 K has been used to generate states of partial reoxidation. The intermediate with the EPR signal at g = 5, 1.78, and 1.69 can be detected as a product of the photolysis and subsequent oxidation but does not appear until the photolyzed sample is incubated at temperatures well above 196 K. In the course of the reoxidation, the intermediate characterized by the g = 5, 1.78, 1.69 signal occurs in the reaction sequence after the states referred to as 'Compound A' and 'Compound B' (Chance, B., Saronio, C., and Leigh, J.S. (1975) J. Biol. Chem. 250, 9226--9237). Its appearance is within the time range reported for the formation of 'oxygenated' cytochrome c oxidase (Orii, Y. (1979) in Cytochrome Oxidase (King, T.E., Orii, Y., Chance, B. and Okunuki, K., eds.), pp. 331--340, Elsevier/North-Holland Biomedical Press, Amsterdam)."}
{"id": "PMID:228711", "title": "The isolation of bovine-heart cytochrome c oxidase subunits. Dependence on phospholipid and cholate-content.", "content": "The polypeptide chains of bovine-heart cytochrome c oxidase were preparatively isolated by a simple large-scale procedure based on gel permeation chromatography in the presence of sodium dodecyl sulphate. The resolution of the subunits as a function of the cholate and phospholipid content of the preparation was investigated. Cholate, and to a lesser extent, phospholipids interfere with the separation of the subunits; however, they do not prevent dissociation of the enzyme by SDS. Bovine-heart cytochrome c oxidase consists of six major subunits (estimated molecular weights in thousands: 40, 25, 20, 14, 12 and 10). In addition, the enzyme preparation contains at least five minor constituents, present in less than stoichiometric amounts. The first two of the three large subunits, all of which are hydrophobic, have amino-terminal N-formylmethionine. Subunit III, however, has a free methionine N-terminus.", "contents": "The isolation of bovine-heart cytochrome c oxidase subunits. Dependence on phospholipid and cholate-content. The polypeptide chains of bovine-heart cytochrome c oxidase were preparatively isolated by a simple large-scale procedure based on gel permeation chromatography in the presence of sodium dodecyl sulphate. The resolution of the subunits as a function of the cholate and phospholipid content of the preparation was investigated. Cholate, and to a lesser extent, phospholipids interfere with the separation of the subunits; however, they do not prevent dissociation of the enzyme by SDS. Bovine-heart cytochrome c oxidase consists of six major subunits (estimated molecular weights in thousands: 40, 25, 20, 14, 12 and 10). In addition, the enzyme preparation contains at least five minor constituents, present in less than stoichiometric amounts. The first two of the three large subunits, all of which are hydrophobic, have amino-terminal N-formylmethionine. Subunit III, however, has a free methionine N-terminus."}
{"id": "PMID:228712", "title": "Rates of reduced cytochrome c-ferricyanide binding and electron transfer.", "content": "The oxidation of reduced cytochrome c by ferricyanide has been studied over a wide range of ferricyanide concentrations using a continuous-flow apparatus. The formation of a ferrocytochrome c-ferricyanide complex has been demonstrated and the binding and electron transfer processes separated to give both the oxidation electron transfer rate and the binding rate parameters. The electron transfer rate has been found to be 1.86 . 10(3) s-1 in H2O buffer and 1.36 . 10(3) s-1 in 2H2O demonstrating that a deuterium isotope effect of similar magnitude (R = 1.37) to that found in the cytochrome reactions in photosynthetic bacteria [18] is also found in the reaction studied here. The binding association rate parameters also show a similar deuterium isotope effect suggesting that water rotation may be involved in both the binding of ferricyanide to reduced cytochrome c and the subsequent oxidation electron transfer.", "contents": "Rates of reduced cytochrome c-ferricyanide binding and electron transfer. The oxidation of reduced cytochrome c by ferricyanide has been studied over a wide range of ferricyanide concentrations using a continuous-flow apparatus. The formation of a ferrocytochrome c-ferricyanide complex has been demonstrated and the binding and electron transfer processes separated to give both the oxidation electron transfer rate and the binding rate parameters. The electron transfer rate has been found to be 1.86 . 10(3) s-1 in H2O buffer and 1.36 . 10(3) s-1 in 2H2O demonstrating that a deuterium isotope effect of similar magnitude (R = 1.37) to that found in the cytochrome reactions in photosynthetic bacteria [18] is also found in the reaction studied here. The binding association rate parameters also show a similar deuterium isotope effect suggesting that water rotation may be involved in both the binding of ferricyanide to reduced cytochrome c and the subsequent oxidation electron transfer."}
{"id": "PMID:228713", "title": "Reduction of nitrite to nitrous oxide by a cytoplasmic membrane fraction from the marine denitrifier Pseudomonas perfectomarinus.", "content": "A cytoplasmic membrane fraction from the marine denitrifier Pseudomonas perfectomarinus reduced nitrite to nitrous oxide in a stoichiometric reaction without nitric oxide as free intermediate. The membrane system had a specific requirement for FMN with NAD(P)H as electron donors. Other electron donors were ascorbate-reduced cytochrome c-551 or phenazine methosulfate. The membrane fraction contained tightly bound cytochrome cd which represented only a small portion of the total cytochrome cd of the cell. As further terminal oxidase cytochrome o was identified. The membrane fraction produced also nitrous oxide from nitric oxide, however, at a substantially lower rate than from nitrite when using ascorbate-reduced phenazine methosulfate as electron donor.", "contents": "Reduction of nitrite to nitrous oxide by a cytoplasmic membrane fraction from the marine denitrifier Pseudomonas perfectomarinus. A cytoplasmic membrane fraction from the marine denitrifier Pseudomonas perfectomarinus reduced nitrite to nitrous oxide in a stoichiometric reaction without nitric oxide as free intermediate. The membrane system had a specific requirement for FMN with NAD(P)H as electron donors. Other electron donors were ascorbate-reduced cytochrome c-551 or phenazine methosulfate. The membrane fraction contained tightly bound cytochrome cd which represented only a small portion of the total cytochrome cd of the cell. As further terminal oxidase cytochrome o was identified. The membrane fraction produced also nitrous oxide from nitric oxide, however, at a substantially lower rate than from nitrite when using ascorbate-reduced phenazine methosulfate as electron donor."}
{"id": "PMID:228714", "title": "Transfer of light-induced electron-spin polarization from the intermediary acceptor to the prereduced primary acceptor in the reaction center of photosynthetic bacteria.", "content": "In reaction centers and chromatophores of photosynthetic bacteria strong light-induced emissive ESR signals have been found, not only after a flash but also under continuous illumination. The signal, with g = 2.0048 and delta Hpp = 7.6 G, is only present under reducing conditions in material in which the primary acceptor, ubiquinone, U and its associated high-spin ferrous ion are magnetically uncoupled. its amplitude under continuous illumination is strongly dependent on light intensity and on microwave power. The emissive signal is attributed to the prereduced primary acceptor, U-, which becomes polarized through transfer of spin polarization by a magnetic exchange interaction with the photoreduced, spin polarized intermediary acceptor, I-. A kinetic model is presented which explains the observed dependence of emissivity on light intensity and microwave power. Applying this analysis to the light saturation data, a value of the exchange rate between I- and U- of 4.10(8) s-1 is derived, corresponding to an exchange interaction of 3--5 G.", "contents": "Transfer of light-induced electron-spin polarization from the intermediary acceptor to the prereduced primary acceptor in the reaction center of photosynthetic bacteria. In reaction centers and chromatophores of photosynthetic bacteria strong light-induced emissive ESR signals have been found, not only after a flash but also under continuous illumination. The signal, with g = 2.0048 and delta Hpp = 7.6 G, is only present under reducing conditions in material in which the primary acceptor, ubiquinone, U and its associated high-spin ferrous ion are magnetically uncoupled. its amplitude under continuous illumination is strongly dependent on light intensity and on microwave power. The emissive signal is attributed to the prereduced primary acceptor, U-, which becomes polarized through transfer of spin polarization by a magnetic exchange interaction with the photoreduced, spin polarized intermediary acceptor, I-. A kinetic model is presented which explains the observed dependence of emissivity on light intensity and microwave power. Applying this analysis to the light saturation data, a value of the exchange rate between I- and U- of 4.10(8) s-1 is derived, corresponding to an exchange interaction of 3--5 G."}
{"id": "PMID:228715", "title": "The electron spin relaxation of the electron acceptors of photosystem I reaction centre studied by microwave power saturation.", "content": "Photosystem I particles from spinach were reduced by illumination at 77 K. Under these conditions the one-electrom transfer from P-700 resulted in a reduction of only one acceptor molecule of the reaction centre. The EPR signals at g=2.05, 1.94 and 1.86 were attributed to reduced centre A and the smaller signals at g=2.07, 1.92 and 1.89 to reduced centre B. Reduction of both centres by dithionite in the dark lead to signals at g=2.05, 1.99, 1.96, 1.94, 1.92 and 1.89. Thus, the features at g=2.07 and 1.86 disappeared and new signals at g=1.99 and 1.96 were observed. From the spectral changes it followed that the iron-sulphur centres A and B interact magnetically. Temperature dependent EPR spectra demonstrated a faster electron spin relaxation of centre A than of centre B. These conclusions were corroborated using microwave power saturation of the respective EPR signals. The saturation data of the fully reduced centres A and B could not be fitted using the saturation equation for a one-electron spin system. The magnetic interaction between the (4Fe-4S) CENTRes of the electron acceptors A and B resulted in saturation properties which are simular to those of the 2(4Fe-4S) ferredoxin from Clostridium pasteurianum. For centre X a high proportion of homogeneous broadening of the EPR lines was inferred from the inhomogeneity parameter (b=1.83). It was, therefore, concluded that centre X is most probably an anion radical of chlorophyll. From the low temperature necessary for observing the EPR signal of centre X followed that the drastic relaxation enhancement has to be attributed to a magnetic interaction of the anion radical with iron.", "contents": "The electron spin relaxation of the electron acceptors of photosystem I reaction centre studied by microwave power saturation. Photosystem I particles from spinach were reduced by illumination at 77 K. Under these conditions the one-electrom transfer from P-700 resulted in a reduction of only one acceptor molecule of the reaction centre. The EPR signals at g=2.05, 1.94 and 1.86 were attributed to reduced centre A and the smaller signals at g=2.07, 1.92 and 1.89 to reduced centre B. Reduction of both centres by dithionite in the dark lead to signals at g=2.05, 1.99, 1.96, 1.94, 1.92 and 1.89. Thus, the features at g=2.07 and 1.86 disappeared and new signals at g=1.99 and 1.96 were observed. From the spectral changes it followed that the iron-sulphur centres A and B interact magnetically. Temperature dependent EPR spectra demonstrated a faster electron spin relaxation of centre A than of centre B. These conclusions were corroborated using microwave power saturation of the respective EPR signals. The saturation data of the fully reduced centres A and B could not be fitted using the saturation equation for a one-electron spin system. The magnetic interaction between the (4Fe-4S) CENTRes of the electron acceptors A and B resulted in saturation properties which are simular to those of the 2(4Fe-4S) ferredoxin from Clostridium pasteurianum. For centre X a high proportion of homogeneous broadening of the EPR lines was inferred from the inhomogeneity parameter (b=1.83). It was, therefore, concluded that centre X is most probably an anion radical of chlorophyll. From the low temperature necessary for observing the EPR signal of centre X followed that the drastic relaxation enhancement has to be attributed to a magnetic interaction of the anion radical with iron."}
{"id": "PMID:228716", "title": "Partitioning of electrostatic and conformational contributions in the redox reactions of modified cytochromes c.", "content": "The reduction of acetylated, fully succinylated and dicarboxymethyl horse cytochromes c by the radicals CH3CH(OH), CO2.-, O2.-, and e-aq' and the oxidation of the reduced cytochrome c derivatives by Fe(CN)3-6 were studied using the pulse radiolysis technique. Many of the reactions were also examined as a function of ionic strength. By obtaining rate constants for the reactions of differently charged small molecules redox agents with the differently charged cytochrome c derivatives at both zero ionic strength and infinite ionic strength, electrostatic and conformational contributions to the electron transfer mechanism were effectively partioned from each other in some cases. In regard to cytochrome c electron transfer mechanism, the results, especially those for which conformational influences predominate, are supportive of the electron being transferred in the heme edge region.", "contents": "Partitioning of electrostatic and conformational contributions in the redox reactions of modified cytochromes c. The reduction of acetylated, fully succinylated and dicarboxymethyl horse cytochromes c by the radicals CH3CH(OH), CO2.-, O2.-, and e-aq' and the oxidation of the reduced cytochrome c derivatives by Fe(CN)3-6 were studied using the pulse radiolysis technique. Many of the reactions were also examined as a function of ionic strength. By obtaining rate constants for the reactions of differently charged small molecules redox agents with the differently charged cytochrome c derivatives at both zero ionic strength and infinite ionic strength, electrostatic and conformational contributions to the electron transfer mechanism were effectively partioned from each other in some cases. In regard to cytochrome c electron transfer mechanism, the results, especially those for which conformational influences predominate, are supportive of the electron being transferred in the heme edge region."}
{"id": "PMID:228717", "title": "Chromium oxalate: a new spin label broadening agent for use with thylakoids.", "content": "Potassium tris(oxalato)chromate(III) trihydrate (chromium ixalate) has been shown to be a more useful broadening agent than potassium ferricyanide for the spin label 2,2,6,6-tetramethylpiperidine-N-oxyl-4-amine (Tempamine) in thylakoid suspensions. Our data show that chromium oxalate is less permeable than ferricyanide, does not inhibit thylakoid electron transport or photophosphorylation, and is not photoreduced by thylakoids.", "contents": "Chromium oxalate: a new spin label broadening agent for use with thylakoids. Potassium tris(oxalato)chromate(III) trihydrate (chromium ixalate) has been shown to be a more useful broadening agent than potassium ferricyanide for the spin label 2,2,6,6-tetramethylpiperidine-N-oxyl-4-amine (Tempamine) in thylakoid suspensions. Our data show that chromium oxalate is less permeable than ferricyanide, does not inhibit thylakoid electron transport or photophosphorylation, and is not photoreduced by thylakoids."}
{"id": "PMID:228721", "title": "Correlation between fluidity and fatty acid composition of phospholipid species in Tetrahymena pyriformis during temperature acclimation.", "content": "The correlation between the fluidity of phospholipids and their fatty acid composition was studied by spin label technique and gas-liquid chromatography for three major phospholipid species in Tetrahymena pyriformis during temperature acclimation. The fluidity of 2-aminoethylphosphonolipid increased within the first 10 h of the cold-acclimation when the content of gamma-linolenic acid in 2-aminoethylphosphonolipid was highest, and it then decreased up to 24 h. On the other hand, the fluidities of phosphatidylethanolamine and phosphatidylcholine showed a gradual decrease up to 24 h after the temperature shift, although gamma-linolenic acid contents were highest at 10 h after the temperature shift. Thus the fluidity changes of these two phospholipids were interpreted as resulting from the altered content of other fatty acids in addition to gamma-linolenic acid, since the gamma-linolenic acid content was smaller than that of 2-aminoethylphosphonolipid. The results suggest that the content of gamma-linolenic acid in 2-aminoethylphosphonolipid plays a role in regulating the thermal adaptation process.", "contents": "Correlation between fluidity and fatty acid composition of phospholipid species in Tetrahymena pyriformis during temperature acclimation. The correlation between the fluidity of phospholipids and their fatty acid composition was studied by spin label technique and gas-liquid chromatography for three major phospholipid species in Tetrahymena pyriformis during temperature acclimation. The fluidity of 2-aminoethylphosphonolipid increased within the first 10 h of the cold-acclimation when the content of gamma-linolenic acid in 2-aminoethylphosphonolipid was highest, and it then decreased up to 24 h. On the other hand, the fluidities of phosphatidylethanolamine and phosphatidylcholine showed a gradual decrease up to 24 h after the temperature shift, although gamma-linolenic acid contents were highest at 10 h after the temperature shift. Thus the fluidity changes of these two phospholipids were interpreted as resulting from the altered content of other fatty acids in addition to gamma-linolenic acid, since the gamma-linolenic acid content was smaller than that of 2-aminoethylphosphonolipid. The results suggest that the content of gamma-linolenic acid in 2-aminoethylphosphonolipid plays a role in regulating the thermal adaptation process."}
{"id": "PMID:228723", "title": "Regulation of the intracellular calcium level in human blood platelets: cyclic adenosine 3',5'-monophosphate dependent phosphorylation of a 22,000 dalton component in isolated Ca2+-accumulating vesicles.", "content": "Two protein kinase activities have been separated from the supernatants of homogenized human blood platelets by DEAE cellulose chromatography. One of them (peak I enzyme) is an efficient stimulator of the uptake of Ca2+ into isolated membrane vesicles in the presence of cyclic AMP and ATP. The second (peak II enzyme), although equally active towards histone, exerts only about one third of the activity of the peak I enzyme. The stimulation of Ca2+ uptake is accompanied by the phosphorylation of a membrane protein with an apparent molecular weight of 22 000, which appears to play an essential role in the regulation of the intracellular Ca2+ level and hence of platelet activity.", "contents": "Regulation of the intracellular calcium level in human blood platelets: cyclic adenosine 3',5'-monophosphate dependent phosphorylation of a 22,000 dalton component in isolated Ca2+-accumulating vesicles. Two protein kinase activities have been separated from the supernatants of homogenized human blood platelets by DEAE cellulose chromatography. One of them (peak I enzyme) is an efficient stimulator of the uptake of Ca2+ into isolated membrane vesicles in the presence of cyclic AMP and ATP. The second (peak II enzyme), although equally active towards histone, exerts only about one third of the activity of the peak I enzyme. The stimulation of Ca2+ uptake is accompanied by the phosphorylation of a membrane protein with an apparent molecular weight of 22 000, which appears to play an essential role in the regulation of the intracellular Ca2+ level and hence of platelet activity."}
{"id": "PMID:228728", "title": "Maturation of replicating simian virus 40 DNA molecules in isolated nuclei by continued bidirectional replication to the normal termination region.", "content": "Mature SV40 DNA synthesized for different periods of time either in isolated nuclei or in intact cells was highly purified and then digested with restriction endonucleases in order to relate the time of synthesis of newly replicated viral DNA to its location in the genome. Replication in nuclei supplemented with a cytosol fraction from uninfected cells was a faithful continuation of the bidirectional process observed in intact cells, but did not exhibit significant initiation of new replicons. SV40 DNA replication in cells at 37 degrees C proceeded at about 145 nucleotides/min per replication fork. In the absence of cytosol, when DNA synthesis was limited and joining of Okazaki fragments was retarded, bidirectional SV40 DNA replication continued into the normal region where separation yeilded circular duplex DNA molecules containing one or more interruptions in the nascent DNA strands. In the presence of cytosol, this type of viral DNA was shown to be a precursor of covalently closed, superhelical SV40 DNA, the mature from of viral DNA.", "contents": "Maturation of replicating simian virus 40 DNA molecules in isolated nuclei by continued bidirectional replication to the normal termination region. Mature SV40 DNA synthesized for different periods of time either in isolated nuclei or in intact cells was highly purified and then digested with restriction endonucleases in order to relate the time of synthesis of newly replicated viral DNA to its location in the genome. Replication in nuclei supplemented with a cytosol fraction from uninfected cells was a faithful continuation of the bidirectional process observed in intact cells, but did not exhibit significant initiation of new replicons. SV40 DNA replication in cells at 37 degrees C proceeded at about 145 nucleotides/min per replication fork. In the absence of cytosol, when DNA synthesis was limited and joining of Okazaki fragments was retarded, bidirectional SV40 DNA replication continued into the normal region where separation yeilded circular duplex DNA molecules containing one or more interruptions in the nascent DNA strands. In the presence of cytosol, this type of viral DNA was shown to be a precursor of covalently closed, superhelical SV40 DNA, the mature from of viral DNA."}
{"id": "PMID:228729", "title": "Partial purification, substrate specificity and regulation of alpha-L-glycerolphosphate dehydrogenase from Saccharomyces carlsbergensis.", "content": "alpha-L-Glycerolphosphate dehydrogenase (sn-glycerol-3-phosphate:NAD+ 2-oxidoreductase, EC 1.1.1.8) from Saccharomyces carlsbergensis was purified 400-fold. The enzyme preparation is free of interfering activities, such as glyceraldehyde phosphate dehydrogenase, alcohol dehydrogenase, triose phosphate isomerase and glycerolphosphatase. At pH 7.0 it is specific for NADH (Km = 0.027 mM with 0.8 mM dihydroxyacetone phosphate) and dihydroxyacetone phosphate (Km = 0.2 mM with 0.2 mM NADH). Between pH 5.0 and 6.0 the enzyme functions with NADPH, but only at 7% of the rate with NADH. Various anions (I- greater than SO42- greater than Br- greater than Cl-) act as inhibitors competing with the substrate dihydroxyacetone phosphate. Inorganic phosphate (Ki = 0.1 mM), pyrophosphate and arsenate are strong inhibitors. The nucleotides ATP and ADP are also inhibitory, but their action seems to be of the same type as the general anion competition (Ki = 0.73 mM for ATP). The results are consistent with the notion that the enzyme may regulate the redox potential of the NAD+/NADH couple during fermentation.", "contents": "Partial purification, substrate specificity and regulation of alpha-L-glycerolphosphate dehydrogenase from Saccharomyces carlsbergensis. alpha-L-Glycerolphosphate dehydrogenase (sn-glycerol-3-phosphate:NAD+ 2-oxidoreductase, EC 1.1.1.8) from Saccharomyces carlsbergensis was purified 400-fold. The enzyme preparation is free of interfering activities, such as glyceraldehyde phosphate dehydrogenase, alcohol dehydrogenase, triose phosphate isomerase and glycerolphosphatase. At pH 7.0 it is specific for NADH (Km = 0.027 mM with 0.8 mM dihydroxyacetone phosphate) and dihydroxyacetone phosphate (Km = 0.2 mM with 0.2 mM NADH). Between pH 5.0 and 6.0 the enzyme functions with NADPH, but only at 7% of the rate with NADH. Various anions (I- greater than SO42- greater than Br- greater than Cl-) act as inhibitors competing with the substrate dihydroxyacetone phosphate. Inorganic phosphate (Ki = 0.1 mM), pyrophosphate and arsenate are strong inhibitors. The nucleotides ATP and ADP are also inhibitory, but their action seems to be of the same type as the general anion competition (Ki = 0.73 mM for ATP). The results are consistent with the notion that the enzyme may regulate the redox potential of the NAD+/NADH couple during fermentation."}
{"id": "PMID:228730", "title": "Solution conformation of lactate dehydrogenase as studied by saturation transfer ESR spectroscopy.", "content": "Several binary and ternary inhibitor and 'dead end' complexes of pig heart lactate dehydrogenase (L-lactate:NAD+ oxidoreductase, EC 1.1.1.27) were studied by saturation transfer ESR spectroscopy by means of an active NAD analog, spin-labeled at N6. The mobility of the spin-label depends on the nature of small molecules bound at the remote catalytic end of the coenzyme. The spin-label was found to serve as a reporter group monitoring the conformation of the peptide loop that is folded down over the active cleft in crystals of ternary complexes. The data suggest a fluctuation of the loop between open and closed forms in solution. The structure of the inhibitor molecules has been correlated with their ability to stabilize a more closed conformation of the loop.", "contents": "Solution conformation of lactate dehydrogenase as studied by saturation transfer ESR spectroscopy. Several binary and ternary inhibitor and 'dead end' complexes of pig heart lactate dehydrogenase (L-lactate:NAD+ oxidoreductase, EC 1.1.1.27) were studied by saturation transfer ESR spectroscopy by means of an active NAD analog, spin-labeled at N6. The mobility of the spin-label depends on the nature of small molecules bound at the remote catalytic end of the coenzyme. The spin-label was found to serve as a reporter group monitoring the conformation of the peptide loop that is folded down over the active cleft in crystals of ternary complexes. The data suggest a fluctuation of the loop between open and closed forms in solution. The structure of the inhibitor molecules has been correlated with their ability to stabilize a more closed conformation of the loop."}
{"id": "PMID:228731", "title": "Autoinactivation of xanthine oxidase: the role of superoxide radical and hydrogen peroxide.", "content": "Xanthine oxidase suffers autoinactivation in the course of catalyzing the oxidation of acetaldehyde. When no special efforts were made to maintain a high pO2 in these reaction mixtures catalase protected the xanthine oxidase, but superoxide dismutase did not. However, when oxygen depletion was slowed or prevented by working at lower concentrations of xanthine oxidase, at lower temperatures or by vigorous agitation under an atmosphere of 100% oxygen, superoxide dismutase or catalase protected markedly when added separately and protected almost completely when added together. This result correlates with the greater production of O2-, relative to H2O2, by xanthine oxidase, at elevated pO2. Since histidine also provided some protection and the high levels of acetaldehyde used would have precluded any significant effect of OH., we conclude that singlet oxygen, or something with similar reactivity, was generated from O2- plus H2O2 and contributed significantly to the observed autoinactivation.", "contents": "Autoinactivation of xanthine oxidase: the role of superoxide radical and hydrogen peroxide. Xanthine oxidase suffers autoinactivation in the course of catalyzing the oxidation of acetaldehyde. When no special efforts were made to maintain a high pO2 in these reaction mixtures catalase protected the xanthine oxidase, but superoxide dismutase did not. However, when oxygen depletion was slowed or prevented by working at lower concentrations of xanthine oxidase, at lower temperatures or by vigorous agitation under an atmosphere of 100% oxygen, superoxide dismutase or catalase protected markedly when added separately and protected almost completely when added together. This result correlates with the greater production of O2-, relative to H2O2, by xanthine oxidase, at elevated pO2. Since histidine also provided some protection and the high levels of acetaldehyde used would have precluded any significant effect of OH., we conclude that singlet oxygen, or something with similar reactivity, was generated from O2- plus H2O2 and contributed significantly to the observed autoinactivation."}
{"id": "PMID:228732", "title": "ESR study of free and immobilized elastase.", "content": "Porcine pancreatic elastase (EC 3.4.21.11) has been immobilized on polyacrylamide beads using glutaraldehyde ad bridging reagent without important loss of catalytic activity. A nitroxide spin label, 1-oxyl-2,2,5,5-tetramethyl-4-piperidinyl-ethylphosphonofluoridate, reacting covalently with the serine-195 residue of the active centre of free elastase was used as a conformational and dynamical electron spin resonance probe. This signal is quenched by (Cu2+) which bind specifically at the active site at a distance of 7 A from the nitroxide group. This distance is not significantly affected by the fixation on the solid support. The electron spin resonance lineshape analysis indicates some mobility of the spin label with respect to the native protein. This restricted motion, which is pH dependent, is not noticeably modified by the immobilization of the enzyme. This immobilization has therefore induced no large conformational change of the protein in the vicinity of the active centre. Thermal denaturation of elastase in homogeneous solution is irreversible. Immobilization on the polyacrylamide beads results in 70% reversibility, but the temperature of denaturation is not modified.", "contents": "ESR study of free and immobilized elastase. Porcine pancreatic elastase (EC 3.4.21.11) has been immobilized on polyacrylamide beads using glutaraldehyde ad bridging reagent without important loss of catalytic activity. A nitroxide spin label, 1-oxyl-2,2,5,5-tetramethyl-4-piperidinyl-ethylphosphonofluoridate, reacting covalently with the serine-195 residue of the active centre of free elastase was used as a conformational and dynamical electron spin resonance probe. This signal is quenched by (Cu2+) which bind specifically at the active site at a distance of 7 A from the nitroxide group. This distance is not significantly affected by the fixation on the solid support. The electron spin resonance lineshape analysis indicates some mobility of the spin label with respect to the native protein. This restricted motion, which is pH dependent, is not noticeably modified by the immobilization of the enzyme. This immobilization has therefore induced no large conformational change of the protein in the vicinity of the active centre. Thermal denaturation of elastase in homogeneous solution is irreversible. Immobilization on the polyacrylamide beads results in 70% reversibility, but the temperature of denaturation is not modified."}
{"id": "PMID:228733", "title": "Separation of collagenase and a metal-dependent endopeptidase of rat uterus that hydrolyzes a heptapeptide related to collagen.", "content": "1. The synthetic peptide, 2,4-dinitrophenyl-L-Pro-L-Leu-Gly-L-Ile-L-Ala-Gly-L-Arg-amide (DNP-peptide) was tested as a potential substrate for uterine collagenase. Rat uteri were homogenized and the insoluble fraction was extracted at 60 degrees C to obtain collagenase. The extracts were chromatographed on Sephadex G-150 to yield two peaks of DNP-peptide hydrolyzing activity. Peak I was completely inhibited by EDTA and had a molecular weight greater than 100 000. Peak II was inhibited about 90% by EDTA and had an apparent molecular weight of about 70 000. 2. Peak II coincided closely, but not exactly, with the peak of collagenase activity. It differed from collagenase in heat stability, binding properties on CM-Sephadex and failure to display latency. 3. Peak II represents a new endopeptidase activity. It has a pH optimum of 7 and it cleaves the DNP-peptide at the Gly-Ile and, possibly, the Leu-Gly bond. 4. The DNP-peptide is not a satisfactory substrate for the assay of impure collagenase preparations nor does it inhibit the action of collagenase on collagen substrate when added in 30-fold molar excess.", "contents": "Separation of collagenase and a metal-dependent endopeptidase of rat uterus that hydrolyzes a heptapeptide related to collagen. 1. The synthetic peptide, 2,4-dinitrophenyl-L-Pro-L-Leu-Gly-L-Ile-L-Ala-Gly-L-Arg-amide (DNP-peptide) was tested as a potential substrate for uterine collagenase. Rat uteri were homogenized and the insoluble fraction was extracted at 60 degrees C to obtain collagenase. The extracts were chromatographed on Sephadex G-150 to yield two peaks of DNP-peptide hydrolyzing activity. Peak I was completely inhibited by EDTA and had a molecular weight greater than 100 000. Peak II was inhibited about 90% by EDTA and had an apparent molecular weight of about 70 000. 2. Peak II coincided closely, but not exactly, with the peak of collagenase activity. It differed from collagenase in heat stability, binding properties on CM-Sephadex and failure to display latency. 3. Peak II represents a new endopeptidase activity. It has a pH optimum of 7 and it cleaves the DNP-peptide at the Gly-Ile and, possibly, the Leu-Gly bond. 4. The DNP-peptide is not a satisfactory substrate for the assay of impure collagenase preparations nor does it inhibit the action of collagenase on collagen substrate when added in 30-fold molar excess."}
{"id": "PMID:228734", "title": "The effect of feeding rats with partially hydrogenated marine oil or rapeseed oil on the chain shortening of erucic acid in perfused heart.", "content": "1. The metabolism of [14(-14)C]erucic acid and [U-14C]palmitic acid was studied in perfused hearts from rats fed diets containing hydrogenated marine oil, rapeseed oil or peanut oil for three weeks. 2. [14C]Erucic acid was shortened to [14C]eicosenoic acid (20 : 1, n -- 9) and [14C]oleic acid (18 : 1, n -- 9) in perfused rat hearts from all diet groups. The rapeseed oil diet caused a three-fold increase and the marine oil diet a four-fold increase in the amount of chain-shortened products recovered in heart lipids at the end of perfusion, compared to peanut oil diet. 3. The content of C16:1, C18:1 and C20:1 fatty acids was increased in heart lipids of rats fed hydrogenated marine oil or rapseed oil diet, compared to peanut oil diet. 4. Feeding hydrogenated marine oil or rapeseed oil to the rats induced a 85% increase in catalase activity, a 20% increase in the activity of cytochrome oxidase and a 30--40% increase in the content of total CoA in the heart compared to rats fed peanut oil diet. 5. It is suggested that [14(-14)C]erucic acid is shortened by the beta-oxidation system of peroxisomes in the heart. The increased chain shortening in the hearts from animals fed rapeseed oil or partially hydrogenated marine oil for three weeks may be an important part of an adaptation process.", "contents": "The effect of feeding rats with partially hydrogenated marine oil or rapeseed oil on the chain shortening of erucic acid in perfused heart. 1. The metabolism of [14(-14)C]erucic acid and [U-14C]palmitic acid was studied in perfused hearts from rats fed diets containing hydrogenated marine oil, rapeseed oil or peanut oil for three weeks. 2. [14C]Erucic acid was shortened to [14C]eicosenoic acid (20 : 1, n -- 9) and [14C]oleic acid (18 : 1, n -- 9) in perfused rat hearts from all diet groups. The rapeseed oil diet caused a three-fold increase and the marine oil diet a four-fold increase in the amount of chain-shortened products recovered in heart lipids at the end of perfusion, compared to peanut oil diet. 3. The content of C16:1, C18:1 and C20:1 fatty acids was increased in heart lipids of rats fed hydrogenated marine oil or rapseed oil diet, compared to peanut oil diet. 4. Feeding hydrogenated marine oil or rapeseed oil to the rats induced a 85% increase in catalase activity, a 20% increase in the activity of cytochrome oxidase and a 30--40% increase in the content of total CoA in the heart compared to rats fed peanut oil diet. 5. It is suggested that [14(-14)C]erucic acid is shortened by the beta-oxidation system of peroxisomes in the heart. The increased chain shortening in the hearts from animals fed rapeseed oil or partially hydrogenated marine oil for three weeks may be an important part of an adaptation process."}
{"id": "PMID:228735", "title": "Lipid metabolism in germinating seeds. Purification of ethanolamine kinase from soya bean.", "content": "Ethanolamine kinase has been purified to homogeneity from germinating soya bean (Glycine max L.) seeds. The purified enzyme had a molecular weight of 17--19 000 as estimated by gel filtration and sodium dodecyl suphate-polyacrylamide gel electrophoresis. It would not phosphorylate choline, had a Km for ethanolamine of 8 microM and utilised Mg-ATP. The kinase could be purified in a 37 000 molecular weight form (dimer) which would easily dissociate on storage. In contrast to ethanolamine kinase whose activity was unaffected by the presence of choline in the assay system, soya bean choline kinase, although not phosphorylating ethanolamine, was competitively inhibited by the latter. The purification of specific choline and ethanolamine kinases from germinating soya bean confirmed in vivo observations which had indicated separate enzymes.", "contents": "Lipid metabolism in germinating seeds. Purification of ethanolamine kinase from soya bean. Ethanolamine kinase has been purified to homogeneity from germinating soya bean (Glycine max L.) seeds. The purified enzyme had a molecular weight of 17--19 000 as estimated by gel filtration and sodium dodecyl suphate-polyacrylamide gel electrophoresis. It would not phosphorylate choline, had a Km for ethanolamine of 8 microM and utilised Mg-ATP. The kinase could be purified in a 37 000 molecular weight form (dimer) which would easily dissociate on storage. In contrast to ethanolamine kinase whose activity was unaffected by the presence of choline in the assay system, soya bean choline kinase, although not phosphorylating ethanolamine, was competitively inhibited by the latter. The purification of specific choline and ethanolamine kinases from germinating soya bean confirmed in vivo observations which had indicated separate enzymes."}
{"id": "PMID:228736", "title": "Lipoprotein (a) is not a metabolic product of other lipoproteins containing apolipoprotein B.", "content": "125I-Labeled autologous very low density lipoprotein (VLDL) was injected intravenously into three lipoprotein (a) positive individuals. One other lipoprotein (a) positive subject received 125I-labeled VLDL from a a lipoprotein (a) negative donor. Specific activity of apolipoprotein B in VLDL, low density lipoprotein (LDL) and lipoprotein (a) was measured for 5 days. In the lipoprotein (a) fraction only traces of radioactivity could be detected, which were caused by contamination with labeled LDL. No precursor-product relationship existed between apolipoprotein B in VLDL or LDL and apolipoprotein B in lipoprotein (a). One lipoprotein (a)-positive individual was kept on a fat-free diet for 4 days to prevent chylomicron formation; no change in the serum level of lipoprotein (a) could be detected under these conditions. The data of this study indicate that lipoprotein (a) is not a metabolic product of VLDL or LDL. Also chylomicrons are not likely to play role as a precursor for lipoprotein (a). It is concluded that lipoprotein (a) is synthesized as a separate lipoprotein.", "contents": "Lipoprotein (a) is not a metabolic product of other lipoproteins containing apolipoprotein B. 125I-Labeled autologous very low density lipoprotein (VLDL) was injected intravenously into three lipoprotein (a) positive individuals. One other lipoprotein (a) positive subject received 125I-labeled VLDL from a a lipoprotein (a) negative donor. Specific activity of apolipoprotein B in VLDL, low density lipoprotein (LDL) and lipoprotein (a) was measured for 5 days. In the lipoprotein (a) fraction only traces of radioactivity could be detected, which were caused by contamination with labeled LDL. No precursor-product relationship existed between apolipoprotein B in VLDL or LDL and apolipoprotein B in lipoprotein (a). One lipoprotein (a)-positive individual was kept on a fat-free diet for 4 days to prevent chylomicron formation; no change in the serum level of lipoprotein (a) could be detected under these conditions. The data of this study indicate that lipoprotein (a) is not a metabolic product of VLDL or LDL. Also chylomicrons are not likely to play role as a precursor for lipoprotein (a). It is concluded that lipoprotein (a) is synthesized as a separate lipoprotein."}
{"id": "PMID:228737", "title": "Freeze-fracture studies of cytoplasmic inclusions occurring in experimental lipidosis as induced by amphiphilic cationic drugs.", "content": "The ultrastructure of cytoplasmic inclusions, which characterize experimental lipidosis as induced by several amphiphilic cationic drugs, was studied by means of freeze-fracturing and thin-sectioning. Retinal and adrenal tissues of rats chronically treated with high oral doses of chlorphentermine were used. In thin sections the cytoplasmic inclusions, which were previously shown to represent lysosomes overloaded with polar lipids, exhibit lamellated or lattice-like internal patterns. The present freeze-fracture observations are interpreted as to indicate that the lamellated inclusions contain polar lipids in the lamellar phase, whereas those with lattice-like patterns contain polar lipids in a hexagonal phase.", "contents": "Freeze-fracture studies of cytoplasmic inclusions occurring in experimental lipidosis as induced by amphiphilic cationic drugs. The ultrastructure of cytoplasmic inclusions, which characterize experimental lipidosis as induced by several amphiphilic cationic drugs, was studied by means of freeze-fracturing and thin-sectioning. Retinal and adrenal tissues of rats chronically treated with high oral doses of chlorphentermine were used. In thin sections the cytoplasmic inclusions, which were previously shown to represent lysosomes overloaded with polar lipids, exhibit lamellated or lattice-like internal patterns. The present freeze-fracture observations are interpreted as to indicate that the lamellated inclusions contain polar lipids in the lamellar phase, whereas those with lattice-like patterns contain polar lipids in a hexagonal phase."}
{"id": "PMID:228739", "title": "Alterations of high density lipoproteins in experimental cholestasis in the rat.", "content": "High density lipoproteins (HDL) in the plasma from cholestatic rats were studied by gel filtration, polyacrylamide gel electrophoresis and electron microscopy. HDL from cholestatic rats separated into two subfractions, abnormally enlarged particles and smaller ones, on gel filtration through Bio-Gel A 1.5 m. Polyacrylamide gel electrophoresis in 8 M urea revealed that the relative proportion of C-III-3 peptide in C-apoproteins was higher in the two HDL subfractions from cholestatic rats than in normal HDL. Polyacrylamide gel electrophoresis in sodium dodecyl sulfate showed that the abnormally enlarged HDL contained the 'arginine-rich' apoprotein, whereas a band corresponding to 'arginine-rich' apoprotein was only faintly visible in the smaller HDL subfraction. Normal HDL contained much smaller amount 'arginine-rich' apoprotein than the enlarged HDL. In electron microscopy, both of the two subfractions of cholestatic HDL appeared spherical. The abnormally enlarged HDL were consisted of particles with a diameter of 17 +/- 4.5 nm (mean +/- S.D.). The other subfraction contained smaller particles with a diameter (about 10 nm) similar to normal HDL.", "contents": "Alterations of high density lipoproteins in experimental cholestasis in the rat. High density lipoproteins (HDL) in the plasma from cholestatic rats were studied by gel filtration, polyacrylamide gel electrophoresis and electron microscopy. HDL from cholestatic rats separated into two subfractions, abnormally enlarged particles and smaller ones, on gel filtration through Bio-Gel A 1.5 m. Polyacrylamide gel electrophoresis in 8 M urea revealed that the relative proportion of C-III-3 peptide in C-apoproteins was higher in the two HDL subfractions from cholestatic rats than in normal HDL. Polyacrylamide gel electrophoresis in sodium dodecyl sulfate showed that the abnormally enlarged HDL contained the 'arginine-rich' apoprotein, whereas a band corresponding to 'arginine-rich' apoprotein was only faintly visible in the smaller HDL subfraction. Normal HDL contained much smaller amount 'arginine-rich' apoprotein than the enlarged HDL. In electron microscopy, both of the two subfractions of cholestatic HDL appeared spherical. The abnormally enlarged HDL were consisted of particles with a diameter of 17 +/- 4.5 nm (mean +/- S.D.). The other subfraction contained smaller particles with a diameter (about 10 nm) similar to normal HDL."}
{"id": "PMID:228740", "title": "Use of liposomes in probing the uptake of liposomal phosphatidylcholine by rabbit lung in vitro.", "content": "The purpose of this study was to characterize the uptake of liposomal phosphatidylcholine by lung tissue and its subcellular organelles. Multilamellar liposomes were prepared from egg yolk phosphatidylcholine, dicetyl phosphate, and cholesterol (molar ratio 7 : 2 : 1). Liposomal phosphatidylcholine labeled with [1-14C]dipalmitoyl phosphatidylcholine was taken up by lung slices and incorporated into subcellular organelles including lamellar bodies, mitochondria, and microsomes. In addition, when liposomes were incubated with lamellar bodies, mitochondria, or microsomes, the transfer of liposomal phosphatidylcholine to these subcellular fractions was facilitated by the cytosolic fraction. In tissue slice experiments after 1 h of incubation, about 86% of the total radioactivity absorbed by lung slices and subcellular organelles was recovered in phosphatidylcholine. The ratio of the radioactivity of fatty acids at 1- and 2-positions of dipalmitoyl phosphatidylcholine recovered from all fractions was nearly 1 : 1. This suggests that most phosphatidylcholine molecules were taken up intact. In conclusion, this study provides a method using liposomes as a tool for probing the phosphatidylcholine transfer mechanism in lung.", "contents": "Use of liposomes in probing the uptake of liposomal phosphatidylcholine by rabbit lung in vitro. The purpose of this study was to characterize the uptake of liposomal phosphatidylcholine by lung tissue and its subcellular organelles. Multilamellar liposomes were prepared from egg yolk phosphatidylcholine, dicetyl phosphate, and cholesterol (molar ratio 7 : 2 : 1). Liposomal phosphatidylcholine labeled with [1-14C]dipalmitoyl phosphatidylcholine was taken up by lung slices and incorporated into subcellular organelles including lamellar bodies, mitochondria, and microsomes. In addition, when liposomes were incubated with lamellar bodies, mitochondria, or microsomes, the transfer of liposomal phosphatidylcholine to these subcellular fractions was facilitated by the cytosolic fraction. In tissue slice experiments after 1 h of incubation, about 86% of the total radioactivity absorbed by lung slices and subcellular organelles was recovered in phosphatidylcholine. The ratio of the radioactivity of fatty acids at 1- and 2-positions of dipalmitoyl phosphatidylcholine recovered from all fractions was nearly 1 : 1. This suggests that most phosphatidylcholine molecules were taken up intact. In conclusion, this study provides a method using liposomes as a tool for probing the phosphatidylcholine transfer mechanism in lung."}
{"id": "PMID:228742", "title": "Polyphosphorylated glycerolipids mimic adrenocorticotropin-induced stimulation of mitochondrial pregnenolone-synthesis.", "content": "As with adrenocorticotropin pretreatment in vivo, addition of cardiolipin in vitro enhances adrenal mitochondrial pregnenolone synthesis and apparent binding of cholesterol to cytochrome P-450scc. These effects are relatively specific for glycerolipids containing two or more phosphate radicals in the polar head group, and changes in such phospholipids or comparably acting substances may play a role in mediating adrenocorticotropin- or other hormone-induced effects on membrane-associated enzymes.", "contents": "Polyphosphorylated glycerolipids mimic adrenocorticotropin-induced stimulation of mitochondrial pregnenolone-synthesis. As with adrenocorticotropin pretreatment in vivo, addition of cardiolipin in vitro enhances adrenal mitochondrial pregnenolone synthesis and apparent binding of cholesterol to cytochrome P-450scc. These effects are relatively specific for glycerolipids containing two or more phosphate radicals in the polar head group, and changes in such phospholipids or comparably acting substances may play a role in mediating adrenocorticotropin- or other hormone-induced effects on membrane-associated enzymes."}
{"id": "PMID:228743", "title": "Resonance Raman study on yeast cytochrome c peroxidase. Effect of coordination and axial ligands.", "content": "Resonance Raman spectra are reported for native ferric cytochrome c peroxidase, its cyanide and fluoride compounds, those of the ferrous enzyme and its cyanide and carbonyl compounds, and the spectrum of the hydrogen peroxide compound, compound I. Band frequencies of ferric horseradish peroxidase isoenzyme C2 and its derivatives are also given. Comparison of the frequencies of the bands around 1400, 1500, 1560-1580, and 1610-1640 cm-1 with those of other hemoproteins and heme model compounds showed that in ferric highspin compounds in particular the bands are not only spin and oxidation sensitive, as has previously been reported, but that they also reflect the coordination of the heme iron. It is suggested that ferric cytochrome c peroxidase and horseradish peroxidase are pentacoordinated. In the hexacoordinated fluoride, cyanide and carbon monoxide derivatives the bands reflect the spin state and the out-of-plane position of the heme iron. The spectrum of cytochrome c peroxidase compound I supports previous studies that suggest that it has a lowspin heme iron in the Fe(IV) oxidation state.", "contents": "Resonance Raman study on yeast cytochrome c peroxidase. Effect of coordination and axial ligands. Resonance Raman spectra are reported for native ferric cytochrome c peroxidase, its cyanide and fluoride compounds, those of the ferrous enzyme and its cyanide and carbonyl compounds, and the spectrum of the hydrogen peroxide compound, compound I. Band frequencies of ferric horseradish peroxidase isoenzyme C2 and its derivatives are also given. Comparison of the frequencies of the bands around 1400, 1500, 1560-1580, and 1610-1640 cm-1 with those of other hemoproteins and heme model compounds showed that in ferric highspin compounds in particular the bands are not only spin and oxidation sensitive, as has previously been reported, but that they also reflect the coordination of the heme iron. It is suggested that ferric cytochrome c peroxidase and horseradish peroxidase are pentacoordinated. In the hexacoordinated fluoride, cyanide and carbon monoxide derivatives the bands reflect the spin state and the out-of-plane position of the heme iron. The spectrum of cytochrome c peroxidase compound I supports previous studies that suggest that it has a lowspin heme iron in the Fe(IV) oxidation state."}
{"id": "PMID:228744", "title": "Chicken liver amidophosphoribosyltransferase. Ligand-induced alterations in molecular properties.", "content": "A homogeneous amidophosphoribosyltransferase (EC 2.4.2.14) preparation, which was sensitive to purine nucleotide inhibitors, was obtained from chicken liver. From the result of sodium dodecyl sulfate polyacrylamide gel electrophoresis, the subunit weight was estimated to be approximately 58 000. In Tris-HCl buffer, the predominant form of the enzyme had an S20,w of 6.5, Strokes radius of 40 A, and estimated molecular weight of 110 000. Incubation with 5-phosphoribosyl 1-pyrophosphate or Pi resulted in an increase in the S20,w to 9.1--9.5, Strokes radius 50 A, and estimated molecular weight to 200 000. Incubation of the large form with AMP led to a decrease in the molecular wight of the enzyme. It is concluded that chicken liver amidophosphoribosyltransferase is an allosteric protein whose activity is regulated by a series of conformational changes induced by a number of ligands.", "contents": "Chicken liver amidophosphoribosyltransferase. Ligand-induced alterations in molecular properties. A homogeneous amidophosphoribosyltransferase (EC 2.4.2.14) preparation, which was sensitive to purine nucleotide inhibitors, was obtained from chicken liver. From the result of sodium dodecyl sulfate polyacrylamide gel electrophoresis, the subunit weight was estimated to be approximately 58 000. In Tris-HCl buffer, the predominant form of the enzyme had an S20,w of 6.5, Strokes radius of 40 A, and estimated molecular weight of 110 000. Incubation with 5-phosphoribosyl 1-pyrophosphate or Pi resulted in an increase in the S20,w to 9.1--9.5, Strokes radius 50 A, and estimated molecular weight to 200 000. Incubation of the large form with AMP led to a decrease in the molecular wight of the enzyme. It is concluded that chicken liver amidophosphoribosyltransferase is an allosteric protein whose activity is regulated by a series of conformational changes induced by a number of ligands."}
{"id": "PMID:228745", "title": "Temperature dependence of the electronic spin-lattice relaxation time in a 2-iron-2-sulfur protein.", "content": "The ferredoxins are characterized by a strong temperature dependence of the electronic spin-lattice relaxation time T1. The measurement of this dependence above the liquid nitrogen temperature has been presented in earlier work [1] for the 2-iron-2-sulfur ferredoxin of the blue green alga Spirulina maxima. The different relaxation mechanisms which could be efficient in this range were briefly discussed. In the present paper, we extend the measurement of the temperature dependence of T1 to the low temperature range 1.25 to 30 K. From 1.25 K to 13 K, T1 is obtained by the saturating pulse method, whereas the continuous saturation method is used from 8 K to 30 K. The experimental conditions concerning these methods are discussed. The analysis of the temperature dependence curve over the whole range 1.25 K to 133 K shows clearly that different regions must be distinguished. For each region the possible relaxation processes and the corresponding vibrational modes are discussed.", "contents": "Temperature dependence of the electronic spin-lattice relaxation time in a 2-iron-2-sulfur protein. The ferredoxins are characterized by a strong temperature dependence of the electronic spin-lattice relaxation time T1. The measurement of this dependence above the liquid nitrogen temperature has been presented in earlier work [1] for the 2-iron-2-sulfur ferredoxin of the blue green alga Spirulina maxima. The different relaxation mechanisms which could be efficient in this range were briefly discussed. In the present paper, we extend the measurement of the temperature dependence of T1 to the low temperature range 1.25 to 30 K. From 1.25 K to 13 K, T1 is obtained by the saturating pulse method, whereas the continuous saturation method is used from 8 K to 30 K. The experimental conditions concerning these methods are discussed. The analysis of the temperature dependence curve over the whole range 1.25 K to 133 K shows clearly that different regions must be distinguished. For each region the possible relaxation processes and the corresponding vibrational modes are discussed."}
{"id": "PMID:228746", "title": "Calmodulin resolution of multiple peaks of activity by preparative electrofocusing.", "content": "When the supernatant fractions from rat brain homogenates were subjected to preparative electrofocusing in a bed of Sephadex G75, several peaks of calmodulin were resolved. A minor peak representing free calmodulin migrated with a pI of 3.8 --4.4. Other peaks of calmodulin activity were observed with isoelectric points at pH 4.8, 5.2, 6.0 and 6.8. The peak of calmodulin activity at 5.2 co-migrated with phosphodiesterase activity which was stimulated 1.8-fold by calcium. A second peak of phosphodiesterase activity detected at pH 8.0 was stimulated 1.2-fold by calcium and occurred in an area where no calmodulin activity could be detected. If isoelectric focusing was done in the presence of 8 M urea only one peak of calmodulin activity was observed with a pI of 4.0--4.4. It is suggested that the multiple peaks of calmodulin resolved by electrofocusing represent calmodulin associated with various proteins which are subject to modulation by calmodulin and calcium.", "contents": "Calmodulin resolution of multiple peaks of activity by preparative electrofocusing. When the supernatant fractions from rat brain homogenates were subjected to preparative electrofocusing in a bed of Sephadex G75, several peaks of calmodulin were resolved. A minor peak representing free calmodulin migrated with a pI of 3.8 --4.4. Other peaks of calmodulin activity were observed with isoelectric points at pH 4.8, 5.2, 6.0 and 6.8. The peak of calmodulin activity at 5.2 co-migrated with phosphodiesterase activity which was stimulated 1.8-fold by calcium. A second peak of phosphodiesterase activity detected at pH 8.0 was stimulated 1.2-fold by calcium and occurred in an area where no calmodulin activity could be detected. If isoelectric focusing was done in the presence of 8 M urea only one peak of calmodulin activity was observed with a pI of 4.0--4.4. It is suggested that the multiple peaks of calmodulin resolved by electrofocusing represent calmodulin associated with various proteins which are subject to modulation by calmodulin and calcium."}
{"id": "PMID:228747", "title": "EPR spectroscopy of the iron-sulphur cluster and sirohaem in the dissimilatory sulphite reductase (desulphoviridin) from Desulphovibrio gigas.", "content": "Desulphoviridin in the oxidized state showed EPR signals around g = 6, consistent with the sirohaem being in the high-spin ferric state. This was unreactive with sulphite, sulphide or cyanide; but readily reduced by methyl viologen. When the enzyme was treated with Na2S2O4 the sirohaem was slowly reduced and a spectrum of a reduced iron-sulphur cluster at g = 2.07, 1.93, 1.91 appeared over the course of an hour. An intermediate in this reaction was indicated by a free radical signal which appeared within seconds and then gradually disappeared. On treatment with nitrite and reduced methyl viologen, the enzyme gave a spectrum of a nitroxide derivative similar to that seen with plant nitrite reductase. The midpoint reduction potential of the haem was estimated to be -310 mV or less. The iron-sulphur cluster has a very low potential, being only reduced in the presence of free Na2S2O4 around -560 mV. Desulphoviridin can be classed with sirohaem-containing iron-sulphur proteins.", "contents": "EPR spectroscopy of the iron-sulphur cluster and sirohaem in the dissimilatory sulphite reductase (desulphoviridin) from Desulphovibrio gigas. Desulphoviridin in the oxidized state showed EPR signals around g = 6, consistent with the sirohaem being in the high-spin ferric state. This was unreactive with sulphite, sulphide or cyanide; but readily reduced by methyl viologen. When the enzyme was treated with Na2S2O4 the sirohaem was slowly reduced and a spectrum of a reduced iron-sulphur cluster at g = 2.07, 1.93, 1.91 appeared over the course of an hour. An intermediate in this reaction was indicated by a free radical signal which appeared within seconds and then gradually disappeared. On treatment with nitrite and reduced methyl viologen, the enzyme gave a spectrum of a nitroxide derivative similar to that seen with plant nitrite reductase. The midpoint reduction potential of the haem was estimated to be -310 mV or less. The iron-sulphur cluster has a very low potential, being only reduced in the presence of free Na2S2O4 around -560 mV. Desulphoviridin can be classed with sirohaem-containing iron-sulphur proteins."}
{"id": "PMID:228748", "title": "Serum-free culture of Japanese quail kidney cells. Regulation of vitamin D metabolism.", "content": "Cells obtained from male quail kidneys by digestion with collagenase and hyaluronidase were plated and maintained in a chemically defined, serum-free medium. Culture dishes (35 mm) were inoculated with 1.5 . 10(6) cells which became confluent in 5 days. The cells maintained an epithelial-like morphology over the entire culture period. During a 2 h incubation the cells metabolized 25--30% of the 10 nM 25-hydroxyvitamin D-3 (25-OH-D-3) provided. Seven metabolites were chromatographically separated on Sephadex LH-20. Three have been identified as 1 alpha, 25-dihydroxyvitamin D-3 (1,25(OH)2D-3), 24,25-dihydroxyvitamin D-3 (24,25(OH)2D-3) and 1 alpha, 24,25-trihhydroxyvitamin D-3 (1,24,25(OH)3D-3). The activities of the 25-OH-D-3:1 alpha- and 24-hydroxylases increased eight times faster than the cell number in 5 days. Preincubation of the cells with 10 nM 25-OH-D-3 or 1,25(OH)2D-3 decreased 1,25(OH)2D-3 synthesis, and increased both 24,25(OH)2D-3 and metabolite IV synthesis. The decrease in 25-OH-D-3:1 alpha-hydroxylase activity required a 2 h preincubation with 25-OH-D-3, while stimulation of 25-OH-D-3:24-hydroxylase activity and metabolite IV production required a 6 h preincubation. Incubations of cells for 1 h with parathyroid hormone resulted in a 30-fold increase in cyclic AMP in the medium. A 6 h preincubation with parathyroid hormone decreased 24,25(OH)2D-3) synthesis 50% relative to control cells. These results demonstrate the amenability of this system for studying the regulation of 25-OH-D-3 metabolism, as well as its use for other in vitro studies on renal cell function in a chemically defined culture system.", "contents": "Serum-free culture of Japanese quail kidney cells. Regulation of vitamin D metabolism. Cells obtained from male quail kidneys by digestion with collagenase and hyaluronidase were plated and maintained in a chemically defined, serum-free medium. Culture dishes (35 mm) were inoculated with 1.5 . 10(6) cells which became confluent in 5 days. The cells maintained an epithelial-like morphology over the entire culture period. During a 2 h incubation the cells metabolized 25--30% of the 10 nM 25-hydroxyvitamin D-3 (25-OH-D-3) provided. Seven metabolites were chromatographically separated on Sephadex LH-20. Three have been identified as 1 alpha, 25-dihydroxyvitamin D-3 (1,25(OH)2D-3), 24,25-dihydroxyvitamin D-3 (24,25(OH)2D-3) and 1 alpha, 24,25-trihhydroxyvitamin D-3 (1,24,25(OH)3D-3). The activities of the 25-OH-D-3:1 alpha- and 24-hydroxylases increased eight times faster than the cell number in 5 days. Preincubation of the cells with 10 nM 25-OH-D-3 or 1,25(OH)2D-3 decreased 1,25(OH)2D-3 synthesis, and increased both 24,25(OH)2D-3 and metabolite IV synthesis. The decrease in 25-OH-D-3:1 alpha-hydroxylase activity required a 2 h preincubation with 25-OH-D-3, while stimulation of 25-OH-D-3:24-hydroxylase activity and metabolite IV production required a 6 h preincubation. Incubations of cells for 1 h with parathyroid hormone resulted in a 30-fold increase in cyclic AMP in the medium. A 6 h preincubation with parathyroid hormone decreased 24,25(OH)2D-3) synthesis 50% relative to control cells. These results demonstrate the amenability of this system for studying the regulation of 25-OH-D-3 metabolism, as well as its use for other in vitro studies on renal cell function in a chemically defined culture system."}
{"id": "PMID:228749", "title": "Effect of gelatin on the cyclic AMP response of primocultured hog thyroid cells to acute thyrotropin stimulation.", "content": "The cyclic AMP response of cultured hog thyroid cells to acute thyrotropin stimulation was shown to be under a dual regulatory control by thyrotropin: both positive and negative regulation have been described. When added to the culture medium, gelatin (0.25%) promoted the reorganization of the cells into folicle-like structures, as does thyrotropin. Unlike thyrotropin, gelatin did not induce an increase in intracellular cyclic AMP but enhanced the acute cyclic AMP response to thyrotropin in cells cultured in gelatin-containing medium. When both gelatin and thyrotropin were present, the positive effect of low concentrations of hormone (less than 50 microU/ml) was increased whereas the refractory process observed in the presence of higher concentrations of hormone (greater than 50 microU/ml) was unchanged. These effects of gelatin might be mediated by interaction of the denatured collagen molecules with external proteins of the plasma membrane of thyroid cells.", "contents": "Effect of gelatin on the cyclic AMP response of primocultured hog thyroid cells to acute thyrotropin stimulation. The cyclic AMP response of cultured hog thyroid cells to acute thyrotropin stimulation was shown to be under a dual regulatory control by thyrotropin: both positive and negative regulation have been described. When added to the culture medium, gelatin (0.25%) promoted the reorganization of the cells into folicle-like structures, as does thyrotropin. Unlike thyrotropin, gelatin did not induce an increase in intracellular cyclic AMP but enhanced the acute cyclic AMP response to thyrotropin in cells cultured in gelatin-containing medium. When both gelatin and thyrotropin were present, the positive effect of low concentrations of hormone (less than 50 microU/ml) was increased whereas the refractory process observed in the presence of higher concentrations of hormone (greater than 50 microU/ml) was unchanged. These effects of gelatin might be mediated by interaction of the denatured collagen molecules with external proteins of the plasma membrane of thyroid cells."}
{"id": "PMID:228750", "title": "Photoaffinity labeling of three renal cyclic 3',5'-adenosine monophosphate-binding proteins.", "content": "Evidence is presented for the presence of multiple cyclic AMP binding components in the plasma membrane and cytosol fractions of porcine renal cortex and medulla. N6-(Ethyl-2-diazomalonyl)-3',5'-adenosine monophosphate, a photoaffinity label for cyclic AMP binding sites, exhibits non-covalent binding characteristics similar to cyclic AMP in membrane and soluble fractions. Binding data for either compound to the plasma membrane fraction yields biphasic Scatchard plots while triphasic plots are obtained with the dialyzed cytosol. When covalently labeled fractions are separated on SDS-polyacrylamide gel electrophoresis, the cyclic AMP photoaffinity label is found on 49 000 and 130 000 dalton components in each kidney fraction. DEAE-cellulose and gel filtration chromatography of the labeled cortical cytosol fraction establishes that the three components suggested by the binding data correspond to two 49 000 dalton species and a 130 000 component. The 49 000 species have higher affinities for cyclic AMP than the 130 000 component (Ka(1) = 2.0 . 10(9), Ka(2) = 1.7 . 10(8), Ka(3) = 1.0 . 10(7)). The 49 000 components are associated with protein kinase activity while the 130 000 component does not exhibit protein kinase, adenosine deaminase, or cyclic nucleotide phosphodiesterase activity. Immunologic results and effects of phosphorylation and cyclic GMP on cyclic AMP binding further suggest that the 49 000 components are regulatory subunits of cyclic AMP-dependent protein kinases. Cyclic AMP binding to the 130 000 component is markedly inhibited by adenosine and adenine nucleotides, but not cyclic GMP. Thus, this component may reflect an aspect of adenosine control or metabolism which may or may not be a cyclic AMP-related cellular function.", "contents": "Photoaffinity labeling of three renal cyclic 3',5'-adenosine monophosphate-binding proteins. Evidence is presented for the presence of multiple cyclic AMP binding components in the plasma membrane and cytosol fractions of porcine renal cortex and medulla. N6-(Ethyl-2-diazomalonyl)-3',5'-adenosine monophosphate, a photoaffinity label for cyclic AMP binding sites, exhibits non-covalent binding characteristics similar to cyclic AMP in membrane and soluble fractions. Binding data for either compound to the plasma membrane fraction yields biphasic Scatchard plots while triphasic plots are obtained with the dialyzed cytosol. When covalently labeled fractions are separated on SDS-polyacrylamide gel electrophoresis, the cyclic AMP photoaffinity label is found on 49 000 and 130 000 dalton components in each kidney fraction. DEAE-cellulose and gel filtration chromatography of the labeled cortical cytosol fraction establishes that the three components suggested by the binding data correspond to two 49 000 dalton species and a 130 000 component. The 49 000 species have higher affinities for cyclic AMP than the 130 000 component (Ka(1) = 2.0 . 10(9), Ka(2) = 1.7 . 10(8), Ka(3) = 1.0 . 10(7)). The 49 000 components are associated with protein kinase activity while the 130 000 component does not exhibit protein kinase, adenosine deaminase, or cyclic nucleotide phosphodiesterase activity. Immunologic results and effects of phosphorylation and cyclic GMP on cyclic AMP binding further suggest that the 49 000 components are regulatory subunits of cyclic AMP-dependent protein kinases. Cyclic AMP binding to the 130 000 component is markedly inhibited by adenosine and adenine nucleotides, but not cyclic GMP. Thus, this component may reflect an aspect of adenosine control or metabolism which may or may not be a cyclic AMP-related cellular function."}
{"id": "PMID:228751", "title": "Hormonal control of ornithine decarboxylase in isolated liver cells and the effect of ethanol oxidation.", "content": "The regulation of ornithine decarboxylase activity was studied in freshly isolated rat hepatocytes incubated in a chemically defined medium for 5 h. Glucagon, dibutyryl cyclic AMP, insulin and dexamethasone produced dramatic increases in ornithine decarboxylase activity, 6--100-times the basal activity. Actinomycin D inhibited completely the stimulatory action of these substances. With glucagon, dibutyryl cyclic AMP and insulin, the rise in ornithine decarboxylase activity was rapid but transient, peaking at 200 min and then declining rapidly. By contrast, the response to dexamethasone was gradual and sustained in the 5 h incubation. The transient nature of the response to glucagon was unaltered by repeated additions of optimally effective doses of glucagon suggesting the development of 'refractoriness' to the actions of this hormone. Ethanol oxidation inhibited by 50% the stimulation of ornithine decarboxylase by glucagon and dexamethasone and this effect was blocked by 4-methylpyrazole, an inhibitor of alcohol dehydrogenase. Acetate (2.5--20 mM), the metabolic product of hepatic ethanol oxidation, was also effective. The data indicate that glucagon, insulin and glucocorticoids are all effective in stimulating the activity of ornithine decarboxylase in isolated hepatocytes but they differ in their duration and time of peak of action. Additionally, the inhibitory effect of ethanol on the hormonal stimulation of ornithine decarboxylase is dependent on its oxidation and may be mediated by acetate.", "contents": "Hormonal control of ornithine decarboxylase in isolated liver cells and the effect of ethanol oxidation. The regulation of ornithine decarboxylase activity was studied in freshly isolated rat hepatocytes incubated in a chemically defined medium for 5 h. Glucagon, dibutyryl cyclic AMP, insulin and dexamethasone produced dramatic increases in ornithine decarboxylase activity, 6--100-times the basal activity. Actinomycin D inhibited completely the stimulatory action of these substances. With glucagon, dibutyryl cyclic AMP and insulin, the rise in ornithine decarboxylase activity was rapid but transient, peaking at 200 min and then declining rapidly. By contrast, the response to dexamethasone was gradual and sustained in the 5 h incubation. The transient nature of the response to glucagon was unaltered by repeated additions of optimally effective doses of glucagon suggesting the development of 'refractoriness' to the actions of this hormone. Ethanol oxidation inhibited by 50% the stimulation of ornithine decarboxylase by glucagon and dexamethasone and this effect was blocked by 4-methylpyrazole, an inhibitor of alcohol dehydrogenase. Acetate (2.5--20 mM), the metabolic product of hepatic ethanol oxidation, was also effective. The data indicate that glucagon, insulin and glucocorticoids are all effective in stimulating the activity of ornithine decarboxylase in isolated hepatocytes but they differ in their duration and time of peak of action. Additionally, the inhibitory effect of ethanol on the hormonal stimulation of ornithine decarboxylase is dependent on its oxidation and may be mediated by acetate."}
{"id": "PMID:228752", "title": "Biochemical characterization of lysosomes in unfertilized eggs of Xenopus laevis.", "content": "Relations between lysosomes and yolk platelets of amphibian eggs have been suggested. This work demonstrates the presence of acid hydrolases in oocytes induced to ovulate in vitro. About 40% of the acid hydrolases are found in a sedimentable fraction, and, in accordance with the lysosomal concept, they display structural latency. Biochemical data did not indicate any association between lysosomal enzymes and yolk platelets. The mechanism of yolk resorption is discussed and it is suggested that the fusion of lysosomes and yolk platelets might be one of the mechanisms involved in yolk digestion.", "contents": "Biochemical characterization of lysosomes in unfertilized eggs of Xenopus laevis. Relations between lysosomes and yolk platelets of amphibian eggs have been suggested. This work demonstrates the presence of acid hydrolases in oocytes induced to ovulate in vitro. About 40% of the acid hydrolases are found in a sedimentable fraction, and, in accordance with the lysosomal concept, they display structural latency. Biochemical data did not indicate any association between lysosomal enzymes and yolk platelets. The mechanism of yolk resorption is discussed and it is suggested that the fusion of lysosomes and yolk platelets might be one of the mechanisms involved in yolk digestion."}
{"id": "PMID:228753", "title": "Thiol reactivity and the molecular individuality of alpha- and beta-adrenoreceptors in rat liver plasma membranes.", "content": "Whether or not alpha- and beta-adrenoreceptors are non-identical binding sites on the same protein is still an open question. We investigated the effects of sulfhydryl reagents and dithiothreitol on the binding of [3H]dihydroalprenolol and [3H]dihydroergocryptine to beta- and alpha-adrenoreceptors of rat liver plasma membranes. Dithiothreitol inhibited the binding of [3H]dihydroalprenolol to the beta-adrenoreceptor, whereas it had no effect on the specific binding of [3H]dihydroergocryptine to the alpha-adrenoreceptor. In contrast, mersalyl, a mercurial SH reagent, readily blocked the alpha-adrenoreceptor and, although to a lesser extent the beta-adrenoreceptor. The interaction of mersalyl with the alpha-adrenoreceptors was almost instantaneous. In contrast, under the same experimental conditions, the inactivation of the beta-adrenoreceptors was much slower (t 1/2 : 7 min). Finally, a marked difference in the accessibility of the SH groups to mersalyl was observed between the alpha- and beta-adrenoreceptors. The presence of 15 microM (-)-epinephrine or 1.5 microM phentolamine was sufficient to prevent the blockade of the alpha-adrenoreceptor by mersalyl, but inactivation of the beta-adrenoreceptor by mersalyl was not modified by 500 microM (-)-epinephrine and was only slightly decreased by 50 microM (-)-propranolol. Thus, the alpha- and beta-adrenoreceptors from rat liver plasma membranes exhibited biochemical differences which may be interpreted in favor of their molecular individuality.", "contents": "Thiol reactivity and the molecular individuality of alpha- and beta-adrenoreceptors in rat liver plasma membranes. Whether or not alpha- and beta-adrenoreceptors are non-identical binding sites on the same protein is still an open question. We investigated the effects of sulfhydryl reagents and dithiothreitol on the binding of [3H]dihydroalprenolol and [3H]dihydroergocryptine to beta- and alpha-adrenoreceptors of rat liver plasma membranes. Dithiothreitol inhibited the binding of [3H]dihydroalprenolol to the beta-adrenoreceptor, whereas it had no effect on the specific binding of [3H]dihydroergocryptine to the alpha-adrenoreceptor. In contrast, mersalyl, a mercurial SH reagent, readily blocked the alpha-adrenoreceptor and, although to a lesser extent the beta-adrenoreceptor. The interaction of mersalyl with the alpha-adrenoreceptors was almost instantaneous. In contrast, under the same experimental conditions, the inactivation of the beta-adrenoreceptors was much slower (t 1/2 : 7 min). Finally, a marked difference in the accessibility of the SH groups to mersalyl was observed between the alpha- and beta-adrenoreceptors. The presence of 15 microM (-)-epinephrine or 1.5 microM phentolamine was sufficient to prevent the blockade of the alpha-adrenoreceptor by mersalyl, but inactivation of the beta-adrenoreceptor by mersalyl was not modified by 500 microM (-)-epinephrine and was only slightly decreased by 50 microM (-)-propranolol. Thus, the alpha- and beta-adrenoreceptors from rat liver plasma membranes exhibited biochemical differences which may be interpreted in favor of their molecular individuality."}
{"id": "PMID:228754", "title": "Isolation of cardiac myofibrils and myosin light chains with in vivo levels of light chain phosphorylation.", "content": "Conditions are described for the preparation of functional myofibrils and myosin light chains from freeze-clamped beating hearts with the state of light chain phosphorylation chemically 'frozen' during the extraction procedure. Myofibrils were shown to be functionally intact by measurement of Ca2+ binding and ATPase activity. Highly purified cardiac myosin light chains could be routinely isolated from myofibrillar preparations using ethanol fractionation together with ion-exchange chromatography. Analysis of light chains for covalent phosphate indicated that basal levels of phosphorylation of the 18--20 000 dalton light chain of myosin in rabbit hearts beating in situ or in a perfusion apparatus were 0.3--0.4 mol/mol. Covalent phosphate content of the light chain fraction did not change during perfusion of hearts with 10 microM epinephrine.", "contents": "Isolation of cardiac myofibrils and myosin light chains with in vivo levels of light chain phosphorylation. Conditions are described for the preparation of functional myofibrils and myosin light chains from freeze-clamped beating hearts with the state of light chain phosphorylation chemically 'frozen' during the extraction procedure. Myofibrils were shown to be functionally intact by measurement of Ca2+ binding and ATPase activity. Highly purified cardiac myosin light chains could be routinely isolated from myofibrillar preparations using ethanol fractionation together with ion-exchange chromatography. Analysis of light chains for covalent phosphate indicated that basal levels of phosphorylation of the 18--20 000 dalton light chain of myosin in rabbit hearts beating in situ or in a perfusion apparatus were 0.3--0.4 mol/mol. Covalent phosphate content of the light chain fraction did not change during perfusion of hearts with 10 microM epinephrine."}
{"id": "PMID:228755", "title": "Conformation of adenosine 3',5'-monophosphate in solution as studied by the NMR-desert method. II. Self-association and temperature-dependent glycosidic isomerization at pH 7.", "content": "A study has been made of the association and the temperature-dependent conformation of adenosine 3',5'-monophosphate (cyclic AMP) in a neutral aqueous (2H2O) solution by means of proton magnetic resonance chemical shift and relaxation. The concentration and temperature-dependent chemical shifts of H(1'), H(2), and H(8), have enabled us to estimate the self-association constant, Ka = 1.1 +/- 0.3 M-1 at 25 degrees C and thermodynamic parameters delta H = -5.8 +/- 1.5 kcal/mol and delta S (25 degrees C) = -19.0 +/- 3 cal/mol per degree. The NMR-DESERT (Deuterium Substitution Effect on Relaxation Times) method has been utilized for the determination of the syn-anti conformational equilibrium in the monomeric state and for the determination of the mutual orientation of the two adenine rings in the dimeric state of cyclic AMP. The molecules were found to coexist with nearly equimolarity or syn-anti conformers and thermal activation of the molecules perturbs the syn-anti conformational equilibrium to comprise the syn form in preference at higher temperature. The glycosidic isomerization (from anti to syn) was found to be characterized both by a positive enthalpy change and by a positive entropy change. The cyclic AMP molecules prefer to take a 'trans-stacking' conformation in the dimeric state where the two molecules are arranged in such a way that the H(2) of one molecule is close to the H(8) of the other.", "contents": "Conformation of adenosine 3',5'-monophosphate in solution as studied by the NMR-desert method. II. Self-association and temperature-dependent glycosidic isomerization at pH 7. A study has been made of the association and the temperature-dependent conformation of adenosine 3',5'-monophosphate (cyclic AMP) in a neutral aqueous (2H2O) solution by means of proton magnetic resonance chemical shift and relaxation. The concentration and temperature-dependent chemical shifts of H(1'), H(2), and H(8), have enabled us to estimate the self-association constant, Ka = 1.1 +/- 0.3 M-1 at 25 degrees C and thermodynamic parameters delta H = -5.8 +/- 1.5 kcal/mol and delta S (25 degrees C) = -19.0 +/- 3 cal/mol per degree. The NMR-DESERT (Deuterium Substitution Effect on Relaxation Times) method has been utilized for the determination of the syn-anti conformational equilibrium in the monomeric state and for the determination of the mutual orientation of the two adenine rings in the dimeric state of cyclic AMP. The molecules were found to coexist with nearly equimolarity or syn-anti conformers and thermal activation of the molecules perturbs the syn-anti conformational equilibrium to comprise the syn form in preference at higher temperature. The glycosidic isomerization (from anti to syn) was found to be characterized both by a positive enthalpy change and by a positive entropy change. The cyclic AMP molecules prefer to take a 'trans-stacking' conformation in the dimeric state where the two molecules are arranged in such a way that the H(2) of one molecule is close to the H(8) of the other."}
{"id": "PMID:228756", "title": "Effect of nitrogen starvation on the level of adenosine 3',5'-monophosphate in Anabaena variabilis.", "content": "Low levels of adenosine 3',5'-monophosphate (cyclic AMP) were detected in the cyanobacterium Anabaena variabilis using a protein binding assay and two radioisotopic labelling methods. The basal concentration of intracellular cyclic AMP ranged from 0.27 pmol/mg protein in A. variabilis Kutz grown under heterotrophic conditions to 1.0--2.7 pmol/mg protein in A. variabilis strain 377 grown autotrophically. Extracellular cyclic AMP was found to comprise as much as 90% of the total cyclic AMP in rapidly growing cultures. When A. variabilis strain 377 was starved of nitrogen, a 3--4-fold increase in intracellular cyclic AMP was observed during the 24 h period coincident with early heterocyst development.", "contents": "Effect of nitrogen starvation on the level of adenosine 3',5'-monophosphate in Anabaena variabilis. Low levels of adenosine 3',5'-monophosphate (cyclic AMP) were detected in the cyanobacterium Anabaena variabilis using a protein binding assay and two radioisotopic labelling methods. The basal concentration of intracellular cyclic AMP ranged from 0.27 pmol/mg protein in A. variabilis Kutz grown under heterotrophic conditions to 1.0--2.7 pmol/mg protein in A. variabilis strain 377 grown autotrophically. Extracellular cyclic AMP was found to comprise as much as 90% of the total cyclic AMP in rapidly growing cultures. When A. variabilis strain 377 was starved of nitrogen, a 3--4-fold increase in intracellular cyclic AMP was observed during the 24 h period coincident with early heterocyst development."}
{"id": "PMID:228757", "title": "The permeability coefficient of albumin of the isolated rat mesentery. Modification by some mediators of inflammation, cyclic AMP and calcium.", "content": "In order to study the mechanisms whereby mediators of inflammation exert their exudative effects, we used isolated rat mesentery placed as a separation membrane between the two compartments of a diffusion cell. In this experimental arrangement, the permeability coefficient of albumin (PA) can be easily computed from the equilibration rate of 125I-labelled albumin added to one compartment. Histamine, bradykinin, serotonin and prostaglandins A1, A2, E1, E2, F1 alpha and F2 alpha all increased PA to some extent, the maximal values being approx. +60%. Dibutyryl-cyclic AMP, theophylline and isoproterenol also increased PA, thus suggesting involvement of cyclic AMP. Direct measurements of this nucleotide confirmed this hypothesis; furthermore, a linear relation between cyclic AMP levels and PA could be demonstrated. In contrast, cyclic GMP is probably not involved in the control of PA. Calcium-depleted tissues had a low PA (approx. 40% below controls), and did not respond to exogenous prostaglandin E1. These results suggest that transmesenteric passage of albumin is at least partly controlled by cyclic AMP and intracellular Ca2+ levels.", "contents": "The permeability coefficient of albumin of the isolated rat mesentery. Modification by some mediators of inflammation, cyclic AMP and calcium. In order to study the mechanisms whereby mediators of inflammation exert their exudative effects, we used isolated rat mesentery placed as a separation membrane between the two compartments of a diffusion cell. In this experimental arrangement, the permeability coefficient of albumin (PA) can be easily computed from the equilibration rate of 125I-labelled albumin added to one compartment. Histamine, bradykinin, serotonin and prostaglandins A1, A2, E1, E2, F1 alpha and F2 alpha all increased PA to some extent, the maximal values being approx. +60%. Dibutyryl-cyclic AMP, theophylline and isoproterenol also increased PA, thus suggesting involvement of cyclic AMP. Direct measurements of this nucleotide confirmed this hypothesis; furthermore, a linear relation between cyclic AMP levels and PA could be demonstrated. In contrast, cyclic GMP is probably not involved in the control of PA. Calcium-depleted tissues had a low PA (approx. 40% below controls), and did not respond to exogenous prostaglandin E1. These results suggest that transmesenteric passage of albumin is at least partly controlled by cyclic AMP and intracellular Ca2+ levels."}
{"id": "PMID:228758", "title": "Effects of glucose, chloromercuribenzene-p-sulphonic acid and 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid on phosphate efflux from pancreatic islets.", "content": "Collagenase-isolated pancreatic islets of non-inbred ob/ob mice, containing more than 90% beta-cells, were labelled with radioactive orthophosphate (32P or 33P) and then subjected to non-recirculating perifusion. The basal D-glucose concentration in the perifusion medium was 2.8 mM. When the concentration was suddenly raised to 5.6, 8.3 or 16.7 mM, D-glucose promptly elicited a transient and dose-dependent release of radiophosphate. In the presence of 2.8 mM D-glucose, 0.1 mM of the poorly permeating sulphydryl blocker, chloromercuribenzene-p-sulphonic acid, also evoked a phosphate flush resembling the one induced by D-glucose. The basal radiophosphate release was partially inhibited by 1 mM 4-acetamido-4-'-isothiocyanostilbene-2,2'-disulphonic acid. However, the phosphate flush induced by 16.7 mM D-glucose was not noticeably inhibited by 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid. It is concluded that the phosphate flush emanates from beta-cells and that membrane sulphydryl groups may participate in its regulation. Although at least the basal phosphate release may in part represent transmembrane transport through 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid-sensitive anion channels, other mechanisms are also likely to participate in the glucose-induced phosphate flush.", "contents": "Effects of glucose, chloromercuribenzene-p-sulphonic acid and 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid on phosphate efflux from pancreatic islets. Collagenase-isolated pancreatic islets of non-inbred ob/ob mice, containing more than 90% beta-cells, were labelled with radioactive orthophosphate (32P or 33P) and then subjected to non-recirculating perifusion. The basal D-glucose concentration in the perifusion medium was 2.8 mM. When the concentration was suddenly raised to 5.6, 8.3 or 16.7 mM, D-glucose promptly elicited a transient and dose-dependent release of radiophosphate. In the presence of 2.8 mM D-glucose, 0.1 mM of the poorly permeating sulphydryl blocker, chloromercuribenzene-p-sulphonic acid, also evoked a phosphate flush resembling the one induced by D-glucose. The basal radiophosphate release was partially inhibited by 1 mM 4-acetamido-4-'-isothiocyanostilbene-2,2'-disulphonic acid. However, the phosphate flush induced by 16.7 mM D-glucose was not noticeably inhibited by 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid. It is concluded that the phosphate flush emanates from beta-cells and that membrane sulphydryl groups may participate in its regulation. Although at least the basal phosphate release may in part represent transmembrane transport through 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid-sensitive anion channels, other mechanisms are also likely to participate in the glucose-induced phosphate flush."}
{"id": "PMID:228759", "title": "Studies on the neurochemical properties of cystathionine.", "content": "Following the intracerebral administration of [35S]cystathionine, the synaptosome fraction of rat brain was labelled, the greatest uptake of amino acid being associated with hypothalamus. The uptake of [35S]cystathionine by synaptosome preparations isolated from different regions of brain, was typical of that exhibited by amino acids which are not neurotransmitters. Depolarization of the synaptic membrane had no effect on the efflux of [35S]cystathionine from preloaded synaptosomes. The intracerebral administration of cystathionine resulted in an elevation of the levels of brain cyclic AMP, the effect being particularly evident in the cerebellum. Attempts to reproduce this effect in vitro were unsuccessful.", "contents": "Studies on the neurochemical properties of cystathionine. Following the intracerebral administration of [35S]cystathionine, the synaptosome fraction of rat brain was labelled, the greatest uptake of amino acid being associated with hypothalamus. The uptake of [35S]cystathionine by synaptosome preparations isolated from different regions of brain, was typical of that exhibited by amino acids which are not neurotransmitters. Depolarization of the synaptic membrane had no effect on the efflux of [35S]cystathionine from preloaded synaptosomes. The intracerebral administration of cystathionine resulted in an elevation of the levels of brain cyclic AMP, the effect being particularly evident in the cerebellum. Attempts to reproduce this effect in vitro were unsuccessful."}
{"id": "PMID:228760", "title": "Inhibition of alpha-aminoisobutyric acid transport in membrane vesicles from mouse fibroblasts after phosphorylation by cyclic AMP-dependent protein kinase.", "content": "Cyclic AMP-dependent protein kinases from several mammalian sources inhibit Na+-dependent alpha-aminoisobutyric acid transport by membrane vesicles isolated from 3T3 cells. Evidence is provided that phosphorylation of membrane proteins by the enzyme is responsible for the inhibition. Lysis of the vesicles, or a reduction in the intravesicular volume is not the cause of reduced transport. The cyclic AMP-dependent protein kinase and its catalytic subunit phosphorylate a number of membrane proteins. Most of these proteins are phosphorylated, but to a lesser extent in the absence of protein kinase or cyclic AMP. The phosphorylated proteins remain associated with the membranes during hypotonic lysis treatments, which would be expected to release intravesicular contents and loosely associated membrane proteins. 32P-labeled bands detected on sodium dodecyl sulfate polyacrylamide gels after phosphorylation of membranes by the catalytic subunit of the cyclic AMP-dependent kinase are eliminated by treatment with either pronase or 1 N NaOH, but not by ribonuclease nor by phospholipase C. The stability of the incorporated radioactivity to hot acid and hydroxylamine relative to hot base suggests that most of the 32P from [gamma-32P]ATP is incorporated into protein phosphomonoester linkages.", "contents": "Inhibition of alpha-aminoisobutyric acid transport in membrane vesicles from mouse fibroblasts after phosphorylation by cyclic AMP-dependent protein kinase. Cyclic AMP-dependent protein kinases from several mammalian sources inhibit Na+-dependent alpha-aminoisobutyric acid transport by membrane vesicles isolated from 3T3 cells. Evidence is provided that phosphorylation of membrane proteins by the enzyme is responsible for the inhibition. Lysis of the vesicles, or a reduction in the intravesicular volume is not the cause of reduced transport. The cyclic AMP-dependent protein kinase and its catalytic subunit phosphorylate a number of membrane proteins. Most of these proteins are phosphorylated, but to a lesser extent in the absence of protein kinase or cyclic AMP. The phosphorylated proteins remain associated with the membranes during hypotonic lysis treatments, which would be expected to release intravesicular contents and loosely associated membrane proteins. 32P-labeled bands detected on sodium dodecyl sulfate polyacrylamide gels after phosphorylation of membranes by the catalytic subunit of the cyclic AMP-dependent kinase are eliminated by treatment with either pronase or 1 N NaOH, but not by ribonuclease nor by phospholipase C. The stability of the incorporated radioactivity to hot acid and hydroxylamine relative to hot base suggests that most of the 32P from [gamma-32P]ATP is incorporated into protein phosphomonoester linkages."}
{"id": "PMID:228761", "title": "Cyclic 3',5'-AMP phosphodiesterase in Physarum polycephalum. I. Chemotaxis toward inhibitors and cyclic nucleotides.", "content": "The effect of several inhibitors of the enzyme cyclic 3',5'-AMP phosphodiesterase as chemoattractants in Physarum polycephalum was examined. Of the compounds tested, 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Roche 20-1724/001) and 1-ethyl-4-(isopropylidinehydrazino)-1H-pyrazolo-(3,4-b)-pyridine-5-carboxylic acid ethyl ester, hydrochloride (Squibb 20009) were the most potent attractants. 3-Isobutyl-1-methyl xanthine, theophylline, and morin (a flavanoid) were moderate attractants and sometimes gave negative chemotaxis at high concentrations. Cyclic 3',5'-AMP was an effective, but not potent attractant. A repellent effect following the positive chemotactic action was sometimes observed with cyclic 3',5'-AMP at concentrations as high as 1 . 10(-2) M. Dibutyryl cyclic AMP appeared to be a somewhat more potent attractant than cyclic 3',5'-AMP. The 8-thiomethyl and 8-bromoderivatives of cyclic AMP, which are poorly hydrolyzed by the phosphodiesterase, were not attractants in Physarum. Possible participation of cyclic 3',5'-AMP in the directional movement in P. polycephalum is discussed.", "contents": "Cyclic 3',5'-AMP phosphodiesterase in Physarum polycephalum. I. Chemotaxis toward inhibitors and cyclic nucleotides. The effect of several inhibitors of the enzyme cyclic 3',5'-AMP phosphodiesterase as chemoattractants in Physarum polycephalum was examined. Of the compounds tested, 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Roche 20-1724/001) and 1-ethyl-4-(isopropylidinehydrazino)-1H-pyrazolo-(3,4-b)-pyridine-5-carboxylic acid ethyl ester, hydrochloride (Squibb 20009) were the most potent attractants. 3-Isobutyl-1-methyl xanthine, theophylline, and morin (a flavanoid) were moderate attractants and sometimes gave negative chemotaxis at high concentrations. Cyclic 3',5'-AMP was an effective, but not potent attractant. A repellent effect following the positive chemotactic action was sometimes observed with cyclic 3',5'-AMP at concentrations as high as 1 . 10(-2) M. Dibutyryl cyclic AMP appeared to be a somewhat more potent attractant than cyclic 3',5'-AMP. The 8-thiomethyl and 8-bromoderivatives of cyclic AMP, which are poorly hydrolyzed by the phosphodiesterase, were not attractants in Physarum. Possible participation of cyclic 3',5'-AMP in the directional movement in P. polycephalum is discussed."}
{"id": "PMID:228762", "title": "Cyclic 3',5'AMP phosphodiesterase in Physarum polycephalum. II. Kinetic properties.", "content": "Some kinetic characteristics of soluble and particulate cyclic 3',5'-AMP phosphodiesterases from Physarum polycephalum are presented. The nature of enzyme inhibition by various agents is reported. The relationship between various enzyme inhibitors and their reported chemotactic properties in Physarum is examined. The results suggest that the chemoattractant effect of several inhibitors may be related to their ability to inhibit the particulate and extracellular phosphodiesterases, but is unrelated to inhibition of the intracellular enzyme.", "contents": "Cyclic 3',5'AMP phosphodiesterase in Physarum polycephalum. II. Kinetic properties. Some kinetic characteristics of soluble and particulate cyclic 3',5'-AMP phosphodiesterases from Physarum polycephalum are presented. The nature of enzyme inhibition by various agents is reported. The relationship between various enzyme inhibitors and their reported chemotactic properties in Physarum is examined. The results suggest that the chemoattractant effect of several inhibitors may be related to their ability to inhibit the particulate and extracellular phosphodiesterases, but is unrelated to inhibition of the intracellular enzyme."}
{"id": "PMID:228768", "title": "[Two forms of cyclic nucleotide phosphodiesterase and Ca-dependent protein regulator from rabbit skeletal muscles].", "content": "In rabbit skeletal muscle extracts the activity of phosphodiesterase practically insensitive to the increase of Ca2+ concentration from 10(-8) M up to 10(-5) M. The Ca2+-dependent protein regulator is separated from phosphodiesterase at the stage of isolation and purification. The activity of phosphodiesterase devoid of the protein regulator is inhibited by Ca2+ (10(-5)--10(-3) M). An addition of Ca2+-dependent regulator protects the enzyme against inhibition by Ca2+. The Km values for 3',5'-AMP (5 mkM) and 3',5'-GMP (13 mkM) appear to be close; however, the maximal hydrolysis rates for these nucleotides differ considerably (14,0 and 0,25--0,50 nmoles/min/mg of protein). The hydrolysis of 3',5'-AMP is increased 1,6--3,2-fold under the effect of 3',5'-GMP and that of 3',5'-GMP is increased 1,8--2,7-fold under the effect of 3',5'-AMP. Using ion-exchange chromatography it was shown that only 1% of the total activity of skeletal muscle phosphodieterase belongs to the phosphodiesterase sensitive to the activating effect of Ca2+-dependent regulator the activity of this enzymic form is increased 4--5 fold. The Ca2+-dependent regulator of skeletal muscles is inactivated under the effects of trypsin and during gel-filtration is eluted together with the Ca2+-dependent regulator from the heart. The amount of Ca2+-dependent regulator in skeletal muscles is 30 times as low as that in brain and 3 times as low as that in the heart of the rabbit.", "contents": "[Two forms of cyclic nucleotide phosphodiesterase and Ca-dependent protein regulator from rabbit skeletal muscles]. In rabbit skeletal muscle extracts the activity of phosphodiesterase practically insensitive to the increase of Ca2+ concentration from 10(-8) M up to 10(-5) M. The Ca2+-dependent protein regulator is separated from phosphodiesterase at the stage of isolation and purification. The activity of phosphodiesterase devoid of the protein regulator is inhibited by Ca2+ (10(-5)--10(-3) M). An addition of Ca2+-dependent regulator protects the enzyme against inhibition by Ca2+. The Km values for 3',5'-AMP (5 mkM) and 3',5'-GMP (13 mkM) appear to be close; however, the maximal hydrolysis rates for these nucleotides differ considerably (14,0 and 0,25--0,50 nmoles/min/mg of protein). The hydrolysis of 3',5'-AMP is increased 1,6--3,2-fold under the effect of 3',5'-GMP and that of 3',5'-GMP is increased 1,8--2,7-fold under the effect of 3',5'-AMP. Using ion-exchange chromatography it was shown that only 1% of the total activity of skeletal muscle phosphodieterase belongs to the phosphodiesterase sensitive to the activating effect of Ca2+-dependent regulator the activity of this enzymic form is increased 4--5 fold. The Ca2+-dependent regulator of skeletal muscles is inactivated under the effects of trypsin and during gel-filtration is eluted together with the Ca2+-dependent regulator from the heart. The amount of Ca2+-dependent regulator in skeletal muscles is 30 times as low as that in brain and 3 times as low as that in the heart of the rabbit."}
{"id": "PMID:228769", "title": "[Use of immobilized proteinases for purification of sheep smallpox virus].", "content": "A possible use of papain and trypsin immobilized on Biogel P-100 for purification of DNA-containing sheep smallpox viruses was studied. It was shown that the enzymes depolymerize tissue proteins, resulting in a 90% purification of the viruses without causing any considerable morphological changes in the virion structure. It was concluded that fixed proteinases can be effectively used at the final stage of purification of tissue virus-containing suspensions.", "contents": "[Use of immobilized proteinases for purification of sheep smallpox virus]. A possible use of papain and trypsin immobilized on Biogel P-100 for purification of DNA-containing sheep smallpox viruses was studied. It was shown that the enzymes depolymerize tissue proteins, resulting in a 90% purification of the viruses without causing any considerable morphological changes in the virion structure. It was concluded that fixed proteinases can be effectively used at the final stage of purification of tissue virus-containing suspensions."}
{"id": "PMID:228770", "title": "[Molecular-kinetic parameters of thiamine enzymes and the mechanism of antivitamin action of hydroxythiamine in animal organisms].", "content": "The molecula-kinetic parameters (Km, Ki) of three thiamine enzymes, e. g. thiamine pyrophosphokinase (EC 2.7.6.2), pyruvate dehydrogenase (EC 1.2.4.1) and transketolase (EC 2.2.1.1) with respect to the effects of the thiamine antimetabolite hydroxythiamine in the whole animal organism have been compared. It has been shown that only the first two enzymes, which interact competitively with the vitamin, antivitamin or their pyrophosphate ethers, obey the kinetic parameters obtained for the purified enzymes in vitro. The anticoenzymic effect of hydroxythiamine pyrophosphate with respect to transketolase is not observed in vivo at maximal concentration of the anticoenzyme in tissues due to the absence of competitive interactions with thiamine pyrophosphate. The incorporation of the true and false coenzymes into transketolase occurs only during de novo transketolase synthesis (the apoform is absent in tissues, with the exception of erythrocytes) and proceeds slowly with a half-life time equal to 24--30 hrs. After a single injection of hydroxythiamine at a large dose (70--400 mg/kg) the maximal inhibition of the transketolase activity in tissues (liver, heart, kidney, muscle, spleen, lungs adrenal grands) manifests itself by the 48th--72nd hour, when the concentration of free hydroxythiamine and its pyrophosphate is minimal and the whole anticoenzyme is tightly bound to the protein, forming the false holoenzyme. The use of hydroxythiamine for inhibition of pyruvate dehydrogenase or transketolase in animal organism is discussed.", "contents": "[Molecular-kinetic parameters of thiamine enzymes and the mechanism of antivitamin action of hydroxythiamine in animal organisms]. The molecula-kinetic parameters (Km, Ki) of three thiamine enzymes, e. g. thiamine pyrophosphokinase (EC 2.7.6.2), pyruvate dehydrogenase (EC 1.2.4.1) and transketolase (EC 2.2.1.1) with respect to the effects of the thiamine antimetabolite hydroxythiamine in the whole animal organism have been compared. It has been shown that only the first two enzymes, which interact competitively with the vitamin, antivitamin or their pyrophosphate ethers, obey the kinetic parameters obtained for the purified enzymes in vitro. The anticoenzymic effect of hydroxythiamine pyrophosphate with respect to transketolase is not observed in vivo at maximal concentration of the anticoenzyme in tissues due to the absence of competitive interactions with thiamine pyrophosphate. The incorporation of the true and false coenzymes into transketolase occurs only during de novo transketolase synthesis (the apoform is absent in tissues, with the exception of erythrocytes) and proceeds slowly with a half-life time equal to 24--30 hrs. After a single injection of hydroxythiamine at a large dose (70--400 mg/kg) the maximal inhibition of the transketolase activity in tissues (liver, heart, kidney, muscle, spleen, lungs adrenal grands) manifests itself by the 48th--72nd hour, when the concentration of free hydroxythiamine and its pyrophosphate is minimal and the whole anticoenzyme is tightly bound to the protein, forming the false holoenzyme. The use of hydroxythiamine for inhibition of pyruvate dehydrogenase or transketolase in animal organism is discussed."}
{"id": "PMID:228771", "title": "[Electrochemical analysis of microsomal cytochromes].", "content": "The electrochemical behaviour of the electron transfer proteins -- cytochromes b5, c and P-450 was studied by classical polarography and electrolysis with spectrophotometric monitoring. It was shown electrons are directly transferred from the electrode to oxidized cytochromes c and b5. Cytochrome P-450 is not reduced on the electrodes. However, the reduced inactivated from of cytochrome P-420 was detected at high potential values (-1,5 v).", "contents": "[Electrochemical analysis of microsomal cytochromes]. The electrochemical behaviour of the electron transfer proteins -- cytochromes b5, c and P-450 was studied by classical polarography and electrolysis with spectrophotometric monitoring. It was shown electrons are directly transferred from the electrode to oxidized cytochromes c and b5. Cytochrome P-450 is not reduced on the electrodes. However, the reduced inactivated from of cytochrome P-420 was detected at high potential values (-1,5 v)."}
{"id": "PMID:228766", "title": "[Formation of nitrosyl complexes of non-heme iron in the blood of animals in vivo].", "content": "Addition of an increased content of iron together with nitrit to the diet results in the formation of nitrozyl complexes of non-hem iron in rats' blood. The same complexes are recorded 9 hours after intraperitoneal injection of water solution of iron nitrozyl complex with cistein. Binding of non-hem iron nitrozyl complexes with RS-groups of blood protein is discussed. Nitrozyl complexes of non-hem iron in regular blood elements in vitro are obtained.", "contents": "[Formation of nitrosyl complexes of non-heme iron in the blood of animals in vivo]. Addition of an increased content of iron together with nitrit to the diet results in the formation of nitrozyl complexes of non-hem iron in rats' blood. The same complexes are recorded 9 hours after intraperitoneal injection of water solution of iron nitrozyl complex with cistein. Binding of non-hem iron nitrozyl complexes with RS-groups of blood protein is discussed. Nitrozyl complexes of non-hem iron in regular blood elements in vitro are obtained."}
{"id": "PMID:228772", "title": "[Possible role of SV40 T antigen in cell transformation].", "content": "The effect of purified SV40 T antigen on DNA synthesis in isolated nuclei from the confluent culture of CV-1 cells was studied. In the presence of T antigen the incorporation of [3H]TTP into DNA was found to be 2 to 3 times as high as in the control nuclei. The resulting labelled DNA was subjected to alkaline sucrose gradient centrifugation, which revealed the presence of 4S DNA species, corresponding to Okazaki fragments of animal cells. The latter finding suggests a replicative mode of DNA synthesis induced by T antigen. T antigen isolated from the cells infected with SV40 tsA-mutant and kept at a nonpermissive (41 degrees) temperature fails to stimulate DNA synthesis in isolated nuclei from resting cells. On storage at 4 degrees SV40 T antigen gradually loses its ability to stimulate DNA synthesis and by the 8th day even suppresses it when tested on isolated nuclei from a growing cell culture. No effect of T antigen on the endonuclease-induced reparative synthesis of DNA could be observed. The data described suggest that T antigen is directly involved in the control of DNA synthesis in the cells infected or transformed with SV40.", "contents": "[Possible role of SV40 T antigen in cell transformation]. The effect of purified SV40 T antigen on DNA synthesis in isolated nuclei from the confluent culture of CV-1 cells was studied. In the presence of T antigen the incorporation of [3H]TTP into DNA was found to be 2 to 3 times as high as in the control nuclei. The resulting labelled DNA was subjected to alkaline sucrose gradient centrifugation, which revealed the presence of 4S DNA species, corresponding to Okazaki fragments of animal cells. The latter finding suggests a replicative mode of DNA synthesis induced by T antigen. T antigen isolated from the cells infected with SV40 tsA-mutant and kept at a nonpermissive (41 degrees) temperature fails to stimulate DNA synthesis in isolated nuclei from resting cells. On storage at 4 degrees SV40 T antigen gradually loses its ability to stimulate DNA synthesis and by the 8th day even suppresses it when tested on isolated nuclei from a growing cell culture. No effect of T antigen on the endonuclease-induced reparative synthesis of DNA could be observed. The data described suggest that T antigen is directly involved in the control of DNA synthesis in the cells infected or transformed with SV40."}
{"id": "PMID:228773", "title": "[Structural changes of synaptic membranes under the action of specific antisera using the spin probe technique].", "content": "The spin probing technique was used to study the interaction of preparations of rat cerebral cortex synaptic membranes with specific antisera. It was found that the fluidity of membrane matrix largely depended on the nature of physiological processes involving synaptic membranes in vivo. The supramolecular structure of synaptic membranes isolated from the brain of trained animals differed from that of controls. Differences in the properties of synaptic membranes were also revealed during their incubation with specific antisera. The data obtained are interpreted in terms of immunochemical theory of memory and training.", "contents": "[Structural changes of synaptic membranes under the action of specific antisera using the spin probe technique]. The spin probing technique was used to study the interaction of preparations of rat cerebral cortex synaptic membranes with specific antisera. It was found that the fluidity of membrane matrix largely depended on the nature of physiological processes involving synaptic membranes in vivo. The supramolecular structure of synaptic membranes isolated from the brain of trained animals differed from that of controls. Differences in the properties of synaptic membranes were also revealed during their incubation with specific antisera. The data obtained are interpreted in terms of immunochemical theory of memory and training."}
{"id": "PMID:228774", "title": "[Biosynthesis of collagen and other proteins on tightly and loosely bound polyribosomes from chick embryos].", "content": "Free polyribosomes and polyribosomes bound to endoplasmic membranes were isolated from 10-day-old chick embryos by differential centrifugation. The tightly and loosely bound polyribosomal fractions were isolated from the membrane-bound polyribosomes using 0,5 M KCl. The synthesis of collagen and non-collagen proteins on the polyribosomes were studied in a homologous cell-free system. It was shown that the polyribosomes tightly bound to the membranes possess a lower protein-synthesizing activity as compared to free and loosely bound polyribosomes. The amount of bacterial collagenase-cleaved polypeptides in the protein product synthesized on the polyribosomes tightly and loosely bound to the memranes and on free polyribosomes is 31, 23 and 9%, respectively. The data obtained suggest that the loosely bound polyribosomes are actively involved in collagen synthesis and that this fraction is not a contamination of free polyribosomes in the preparations of totally bound polyribosomes. The role of tightly and loosely bound polyribosomes in the formation of the membrane polyribosomal complex is discussed.", "contents": "[Biosynthesis of collagen and other proteins on tightly and loosely bound polyribosomes from chick embryos]. Free polyribosomes and polyribosomes bound to endoplasmic membranes were isolated from 10-day-old chick embryos by differential centrifugation. The tightly and loosely bound polyribosomal fractions were isolated from the membrane-bound polyribosomes using 0,5 M KCl. The synthesis of collagen and non-collagen proteins on the polyribosomes were studied in a homologous cell-free system. It was shown that the polyribosomes tightly bound to the membranes possess a lower protein-synthesizing activity as compared to free and loosely bound polyribosomes. The amount of bacterial collagenase-cleaved polypeptides in the protein product synthesized on the polyribosomes tightly and loosely bound to the memranes and on free polyribosomes is 31, 23 and 9%, respectively. The data obtained suggest that the loosely bound polyribosomes are actively involved in collagen synthesis and that this fraction is not a contamination of free polyribosomes in the preparations of totally bound polyribosomes. The role of tightly and loosely bound polyribosomes in the formation of the membrane polyribosomal complex is discussed."}
{"id": "PMID:228775", "title": "[Study of the Mg2+-ATPase reaction of myosin using the NMR-31P method. Detection of adenylate kinase activity in a purified myosin subfragment I].", "content": "Isolated myosin heads (HMM-S1) were concentrated by ultrafiltration in an \"Amicon\" cell to a concentration of 120 mg/ml. Incubation of HMM-S1 with ATP in the presence of Mg2+ produced an AMP peak in the spectrum of NMR-31P whose size was increasing linearly with the reaction time. It was demonstrated that after heating of the sample the appearance of AMP in the incubation mixture was due to the presence of a small amount of adenylate kinase (or myokinase) in the purified preparation of HMM-S1.", "contents": "[Study of the Mg2+-ATPase reaction of myosin using the NMR-31P method. Detection of adenylate kinase activity in a purified myosin subfragment I]. Isolated myosin heads (HMM-S1) were concentrated by ultrafiltration in an \"Amicon\" cell to a concentration of 120 mg/ml. Incubation of HMM-S1 with ATP in the presence of Mg2+ produced an AMP peak in the spectrum of NMR-31P whose size was increasing linearly with the reaction time. It was demonstrated that after heating of the sample the appearance of AMP in the incubation mixture was due to the presence of a small amount of adenylate kinase (or myokinase) in the purified preparation of HMM-S1."}
{"id": "PMID:228778", "title": "On the possible involvement of ascorbic acid and copper proteins in leukemia: II. Electron spin resonance (ESR) and atomic absorption investigations on erythrocyte ghosts and plasma.", "content": "The effect of ascorbic acid on white ghosts of erythrocytes and plasma has been investigated by means of ESR spectroscopy. Since the spectra obtained are identical to the one obtained with leukemic blood it is concluded that the receptor for vitamin C has to be searched for in membrane and plasma as well. Determination of Cu and Fe by means of atomic absorption spectroscopy revealed that both of the metals are also present in the membrane. In the case of copper, it must exist there as a protein which has not been identified yet. Oxidizing substances, such as KMnO4, reverse the effect produced by ascorbic acid.", "contents": "On the possible involvement of ascorbic acid and copper proteins in leukemia: II. Electron spin resonance (ESR) and atomic absorption investigations on erythrocyte ghosts and plasma. The effect of ascorbic acid on white ghosts of erythrocytes and plasma has been investigated by means of ESR spectroscopy. Since the spectra obtained are identical to the one obtained with leukemic blood it is concluded that the receptor for vitamin C has to be searched for in membrane and plasma as well. Determination of Cu and Fe by means of atomic absorption spectroscopy revealed that both of the metals are also present in the membrane. In the case of copper, it must exist there as a protein which has not been identified yet. Oxidizing substances, such as KMnO4, reverse the effect produced by ascorbic acid."}
{"id": "PMID:228785", "title": "The normal metacarpal index.", "content": "Normal values for the metacarpal index (MCI) in British children and adults have been determined. In infancy before the appearance of the metacarpal epiphyses the index is constant up to about two years of age (5.2 in males and 5.5 in females). During childhood the index rises to reach a peak at about 16 years, and then falls slightly during adult life. The curves produced are almost identical to those previously found in black children, and one set of values may be used for children of either ethnic origin. The left hand should be used to calculate the MCI, and the results expressed as either below the mean for age, or in terms of percentile for age above the mean. Curves are presented showing percentile values. No attempt should be made to produce a clear distinction between normal and abnormal indices, but the percentile value used in conjunction with other clinical findings in the assessment of Marfan's syndrome and other skeletal conditions associated with arachnodactyly.", "contents": "The normal metacarpal index. Normal values for the metacarpal index (MCI) in British children and adults have been determined. In infancy before the appearance of the metacarpal epiphyses the index is constant up to about two years of age (5.2 in males and 5.5 in females). During childhood the index rises to reach a peak at about 16 years, and then falls slightly during adult life. The curves produced are almost identical to those previously found in black children, and one set of values may be used for children of either ethnic origin. The left hand should be used to calculate the MCI, and the results expressed as either below the mean for age, or in terms of percentile for age above the mean. Curves are presented showing percentile values. No attempt should be made to produce a clear distinction between normal and abnormal indices, but the percentile value used in conjunction with other clinical findings in the assessment of Marfan's syndrome and other skeletal conditions associated with arachnodactyly."}
{"id": "PMID:228786", "title": "Simple enucleation and radiotherapy in the treatment of the pleomorphic salivary adenoma of the parotid gland.", "content": "A series of 76 patients with a primary pleomorphic salivary adenoma treated by simple extracapsular enucleation and high energy radiation between 1963 and 1976 is presented. Analysis of the results has shown a very low incidence of complications with only minimal cosmetic deformity. Of the 76 patients, only 5 have been lost to follow-up, 3 patients have died of causes unrelated to the tumour and only 1 patient has developed a recurrence. Further local excision in this patient showed the histological appearances of adenocarcinoma.", "contents": "Simple enucleation and radiotherapy in the treatment of the pleomorphic salivary adenoma of the parotid gland. A series of 76 patients with a primary pleomorphic salivary adenoma treated by simple extracapsular enucleation and high energy radiation between 1963 and 1976 is presented. Analysis of the results has shown a very low incidence of complications with only minimal cosmetic deformity. Of the 76 patients, only 5 have been lost to follow-up, 3 patients have died of causes unrelated to the tumour and only 1 patient has developed a recurrence. Further local excision in this patient showed the histological appearances of adenocarcinoma."}
{"id": "PMID:228783", "title": "The effects of pathophysiologic state on the metabolism of vasoactive peptides by mammalian lung.", "content": "The pulmonary circulation plays a major role in the metabolism of angiotensin I (AI) and bradykinin through the activity of endothelial cell membrane-bound dipeptidylcarboxypeptidase, converting enzyme of kininase II. This report describes studies which investigate the effects of hypoxia on the function of converting enzyme in vivo in dogs and in endothelial cells in culture. Pulmonary converting enzyme function was assessed by both a blood pressure response technique and radioimmunoassay of bradykinin. Conversion of AI in vivo is decreased during acute alveolar hypoxia. At a PaO2 of 30 mmHg, conversion of AI is decreased to one-half control values. This decrease in AI conversion could not be related to hemodynamic factors in the pulmonary vasculature induced by hypoxia. Clearance of bradykinin by lung converting enzyme decreased from 96% at PaO2 levels above 95 torr to 0% below 26 torr. Hypoxic inhibition of enzyme activity was rapid in onset (less than 2 min), was closely correlated with PaO2 (r = 0.92, p less than 0.001) and reversible within 2 min after return to room air breathing. Converting enzyme activity of the systemic vascular bed also is inhibited by hypoxia. Converting enzyme activity also was studied by adding bradykinin or AI to endothelial cells in culture flasks and measuring residual peptide over time by radioimmunoassay. Hypoxia rapidly (less than 2 min) decreased enzyme activity and room air restored it rapidly. There was no enzyme activity below a PO2 of 30 mmHg. Hypoxia does not affect the activity of purified converting enzyme free of the endothelial cell. Metabolic and respiratory acidosis, as well as metabolic and respiratory alkalosis, had no significant effect on converting enzyme function in vivo in intact animals. While converting enzyme is resistant to a number of pathophysiological insults, it is extraordinarily responsive to acute hypoxia which may have important implications for systemic vasomotor control in conditions associated with clinical hypoxia and hypoxemia.", "contents": "The effects of pathophysiologic state on the metabolism of vasoactive peptides by mammalian lung. The pulmonary circulation plays a major role in the metabolism of angiotensin I (AI) and bradykinin through the activity of endothelial cell membrane-bound dipeptidylcarboxypeptidase, converting enzyme of kininase II. This report describes studies which investigate the effects of hypoxia on the function of converting enzyme in vivo in dogs and in endothelial cells in culture. Pulmonary converting enzyme function was assessed by both a blood pressure response technique and radioimmunoassay of bradykinin. Conversion of AI in vivo is decreased during acute alveolar hypoxia. At a PaO2 of 30 mmHg, conversion of AI is decreased to one-half control values. This decrease in AI conversion could not be related to hemodynamic factors in the pulmonary vasculature induced by hypoxia. Clearance of bradykinin by lung converting enzyme decreased from 96% at PaO2 levels above 95 torr to 0% below 26 torr. Hypoxic inhibition of enzyme activity was rapid in onset (less than 2 min), was closely correlated with PaO2 (r = 0.92, p less than 0.001) and reversible within 2 min after return to room air breathing. Converting enzyme activity of the systemic vascular bed also is inhibited by hypoxia. Converting enzyme activity also was studied by adding bradykinin or AI to endothelial cells in culture flasks and measuring residual peptide over time by radioimmunoassay. Hypoxia rapidly (less than 2 min) decreased enzyme activity and room air restored it rapidly. There was no enzyme activity below a PO2 of 30 mmHg. Hypoxia does not affect the activity of purified converting enzyme free of the endothelial cell. Metabolic and respiratory acidosis, as well as metabolic and respiratory alkalosis, had no significant effect on converting enzyme function in vivo in intact animals. While converting enzyme is resistant to a number of pathophysiological insults, it is extraordinarily responsive to acute hypoxia which may have important implications for systemic vasomotor control in conditions associated with clinical hypoxia and hypoxemia."}
{"id": "PMID:228784", "title": "Does impaired diffusion for oxygen exist in diseased lungs?", "content": "The historical development of ideas concerning impairment of diffusion in the lungs (alveolar-capillary block) is described. The major publications by Riley and Cournand, and others, which showed that impairment of diffusion exists in some diseased lungs were based on careful measurements of the arterial oxygen tension or saturation of patients. These papers described work carried out in the State of New York. Other workers claim to have shown that impairment of diffusion does not exist in diseased lungs: the impairment of oxygen transfer in alveolar-capillary block is said to be due to uneven ventilation-perfusion ratios. The publications which adopt this point of view are mostly based on measurements of the concentration of inert gases in the arterial blood. By chance, the workers who found that diffusion is not impaired in diseased lungs were all in the State of California. It is pointed out here that the California workers have failed to recognize that diffusion, like ventilation and perfusion, is distributed, i.e. varies greatly in different alveoli. This led them to ignore the fact that in some alveoli in diseased lungs, diffusion is so greatly impaired that some inert gases do not reach equilibrium at the end of the pulmonary capillary: the tension of inert gas in end-capillary blood is different from the tension of the same gas in alveolar gas. This invalidates the basic assumption underlying the inert gas method.", "contents": "Does impaired diffusion for oxygen exist in diseased lungs? The historical development of ideas concerning impairment of diffusion in the lungs (alveolar-capillary block) is described. The major publications by Riley and Cournand, and others, which showed that impairment of diffusion exists in some diseased lungs were based on careful measurements of the arterial oxygen tension or saturation of patients. These papers described work carried out in the State of New York. Other workers claim to have shown that impairment of diffusion does not exist in diseased lungs: the impairment of oxygen transfer in alveolar-capillary block is said to be due to uneven ventilation-perfusion ratios. The publications which adopt this point of view are mostly based on measurements of the concentration of inert gases in the arterial blood. By chance, the workers who found that diffusion is not impaired in diseased lungs were all in the State of California. It is pointed out here that the California workers have failed to recognize that diffusion, like ventilation and perfusion, is distributed, i.e. varies greatly in different alveoli. This led them to ignore the fact that in some alveoli in diseased lungs, diffusion is so greatly impaired that some inert gases do not reach equilibrium at the end of the pulmonary capillary: the tension of inert gas in end-capillary blood is different from the tension of the same gas in alveolar gas. This invalidates the basic assumption underlying the inert gas method."}
{"id": "PMID:228789", "title": "Viral infections in renal allograft recipients treated with long-term immunosuppression.", "content": "Thirty-nine renal allograft recipients who had received continuous immunosuppression for six to 13 years were examined clinically and virologically for evidence of past or present viral infection. Twenty-five had common warts, usually on the hands. In most the warts had appeared about one year after transplantation; once present, they never disappeared. Six patients had had a zoster rash from two months to four years after transplantation. None had had jaundice, and there was no change in the frequency of colds or non-specific fibrile illness. Four patients had no cytomegalovirus complement-fixing antibodies throughout the observation period; in the other 35 the antibody titre had risen appreciably during the first three to four months after transplantation. Antibody titres were high (mean 64) at follow-up, being only slightly lower than the highest titres achieved during the immediate postoperative period. None of the patients had had symptomatic cytomegalovirus infection, and in only two was the virus isolated from the urine at follow-up; the titres were extremely low. No changes occurred in the frequency of herpes simplex eruptions. Although all patients had herpes simplex humoral antibody, none excreted the virus. Although cytomegalovirus antibody titres were high, virus excretion was rare, indicating that chronic cytomegalovirus infection in these patients is immunologically well controlled.", "contents": "Viral infections in renal allograft recipients treated with long-term immunosuppression. Thirty-nine renal allograft recipients who had received continuous immunosuppression for six to 13 years were examined clinically and virologically for evidence of past or present viral infection. Twenty-five had common warts, usually on the hands. In most the warts had appeared about one year after transplantation; once present, they never disappeared. Six patients had had a zoster rash from two months to four years after transplantation. None had had jaundice, and there was no change in the frequency of colds or non-specific fibrile illness. Four patients had no cytomegalovirus complement-fixing antibodies throughout the observation period; in the other 35 the antibody titre had risen appreciably during the first three to four months after transplantation. Antibody titres were high (mean 64) at follow-up, being only slightly lower than the highest titres achieved during the immediate postoperative period. None of the patients had had symptomatic cytomegalovirus infection, and in only two was the virus isolated from the urine at follow-up; the titres were extremely low. No changes occurred in the frequency of herpes simplex eruptions. Although all patients had herpes simplex humoral antibody, none excreted the virus. Although cytomegalovirus antibody titres were high, virus excretion was rare, indicating that chronic cytomegalovirus infection in these patients is immunologically well controlled."}
{"id": "PMID:228790", "title": "Epidemic of amoebiasis and giardiasis in a biased population.", "content": "Of 126 homosexual men in a selected population in New York City, 31.7% were infected with Entamoeba histolytica, 18.3% with Giardia lamblia, and 39.7% with one or both on a single stool examination. Of 5885 clinic and hospital patients examined in the same laboratory by the same methods, 1.3% were infected with E. histolytica, 2.1% with G. lamblia, and 3.3% with one or both. Evidence indicates that an epidemic of intestinal protozoan infection exists in the homosexual male population in New York City. The difficulty in making a diagnosis, inadequate therapy, failure to alert potential victims, and official neglect of the epidemic have combined to create a dangerous situation.", "contents": "Epidemic of amoebiasis and giardiasis in a biased population. Of 126 homosexual men in a selected population in New York City, 31.7% were infected with Entamoeba histolytica, 18.3% with Giardia lamblia, and 39.7% with one or both on a single stool examination. Of 5885 clinic and hospital patients examined in the same laboratory by the same methods, 1.3% were infected with E. histolytica, 2.1% with G. lamblia, and 3.3% with one or both. Evidence indicates that an epidemic of intestinal protozoan infection exists in the homosexual male population in New York City. The difficulty in making a diagnosis, inadequate therapy, failure to alert potential victims, and official neglect of the epidemic have combined to create a dangerous situation."}
{"id": "PMID:228791", "title": "Ultrastructural changes in polymyositis.", "content": "Muscle biopsies from 32 cases with polymyositis and dermatomyositis were examined by electron microscopy. Most of the changes of the muscle fibres were non-specific and little structural difference was seen in the various clinical types. The muscle fibres sometimes showed rough endoplasmic reticulum, annulate lamellae and prominent Golgi apparatus. Thin and thick filamentous inclusions were present both in the sarcoplasm and nuclei of some muscle fibres. Thick filamentous inclusions were seen in chronic cases and were sometimes associated with annulate lamellae. Regeneration of muscle was often conspicuous. The endothelial cells of the blood vessels were hypertrophied; some cells contained granulotubular inclusions, rod-shaped bodies (Weibel-Palade bodies) and filamentous material. The basement membrane of the vessels was often multi-layered. The cells infiltrating the interstitial tissue included macrophages, lymphocytes, transformed lymphocytes, plasma cells, monocytes, mast cells and only occasional eosinophils and basophils. Lymphocytes, macrophages and a few plasma cells were seen between the plasma and basement membranes of degenerating muscle fibres. Changes were also noted in some intramuscular nerves, motor end-plates and a muscle spindle.", "contents": "Ultrastructural changes in polymyositis. Muscle biopsies from 32 cases with polymyositis and dermatomyositis were examined by electron microscopy. Most of the changes of the muscle fibres were non-specific and little structural difference was seen in the various clinical types. The muscle fibres sometimes showed rough endoplasmic reticulum, annulate lamellae and prominent Golgi apparatus. Thin and thick filamentous inclusions were present both in the sarcoplasm and nuclei of some muscle fibres. Thick filamentous inclusions were seen in chronic cases and were sometimes associated with annulate lamellae. Regeneration of muscle was often conspicuous. The endothelial cells of the blood vessels were hypertrophied; some cells contained granulotubular inclusions, rod-shaped bodies (Weibel-Palade bodies) and filamentous material. The basement membrane of the vessels was often multi-layered. The cells infiltrating the interstitial tissue included macrophages, lymphocytes, transformed lymphocytes, plasma cells, monocytes, mast cells and only occasional eosinophils and basophils. Lymphocytes, macrophages and a few plasma cells were seen between the plasma and basement membranes of degenerating muscle fibres. Changes were also noted in some intramuscular nerves, motor end-plates and a muscle spindle."}
{"id": "PMID:228792", "title": "Morphological characterization of slow and fast pyramidal tract cells in the cat.", "content": "In adult cats the morphology of slow and fast pyramidal tract (Pt) neurons was studied following intracellular HRP injections and Golgi impregnation. Both types of neurons are pyramidal cells and their soma are all located in the fifth layer of the motor area. As a rule, fast Pt neurons have large somata and their basal and apical dendrites occupy a larger territory in the tangential plane. In layer I, terminal apical dendrites of fast Pt neurons are smooth and divide poorly while those of slow Pt neurons bear a moderate amount of spines and branch profusely. Midway between the pia and layer V, in the third layer, the apical shafts of both types of Pt cells run upward with little branching. These shafts are more numerous in fast Pt cells (7 to 16) and they are almost devoid of spines. Those of slow Pt cells in layer III number between 5 and 9 and are densely covered with spines. Oblique and horizontal branches of slow and fast Pt neurons extend in layer V and some of them invade the lower part of layer III. It is suggested that this zone corresponds to a true fourth layer in the motor area. In both types of cells oblique and lateral branches bear numerous spines. Within the basal dendritic territory of Pt cells, one has to distinguish two dendritic systems: a short and a long one. The former spreads downward obliquely and appears to remain within layer V. The latter is made up of long descending vertical (antiapical) and oblique dendrites (tap root). While both types of cells may have long antiapical dendrites that run down radially to the lower part of layer VI, tap root dendrites which expand laterally below the cell body for considerable distances are a distinctive feature of fast Pt neurons. Though basal dendrites of all Pt cells bear spines, their number, distribution and shape are very variable in fast Pt cells.", "contents": "Morphological characterization of slow and fast pyramidal tract cells in the cat. In adult cats the morphology of slow and fast pyramidal tract (Pt) neurons was studied following intracellular HRP injections and Golgi impregnation. Both types of neurons are pyramidal cells and their soma are all located in the fifth layer of the motor area. As a rule, fast Pt neurons have large somata and their basal and apical dendrites occupy a larger territory in the tangential plane. In layer I, terminal apical dendrites of fast Pt neurons are smooth and divide poorly while those of slow Pt neurons bear a moderate amount of spines and branch profusely. Midway between the pia and layer V, in the third layer, the apical shafts of both types of Pt cells run upward with little branching. These shafts are more numerous in fast Pt cells (7 to 16) and they are almost devoid of spines. Those of slow Pt cells in layer III number between 5 and 9 and are densely covered with spines. Oblique and horizontal branches of slow and fast Pt neurons extend in layer V and some of them invade the lower part of layer III. It is suggested that this zone corresponds to a true fourth layer in the motor area. In both types of cells oblique and lateral branches bear numerous spines. Within the basal dendritic territory of Pt cells, one has to distinguish two dendritic systems: a short and a long one. The former spreads downward obliquely and appears to remain within layer V. The latter is made up of long descending vertical (antiapical) and oblique dendrites (tap root). While both types of cells may have long antiapical dendrites that run down radially to the lower part of layer VI, tap root dendrites which expand laterally below the cell body for considerable distances are a distinctive feature of fast Pt neurons. Though basal dendrites of all Pt cells bear spines, their number, distribution and shape are very variable in fast Pt cells."}
{"id": "PMID:228793", "title": "Differential atrophy of sensory and motor fibers following section of cat peripheral nerves.", "content": "Differential effects of peripheral nerve section on myelinated sensory and motor fiber populations were investigated in 5 hindlimb nerves of cats. Upon electrical stimulation of each nerve, monophasic compound action potentials were recorded from the L6, L7 and S1 dorsal and ventral roots, and the impedance of each root was measured. The decline in the electrical charge computed from potentials 43 to 252 days after nerve section gave a measure of the effect of axotomy on the diameters of sensory and of motor fibers in each nerve. No significant difference in the rate of atrophy of sensory and motor fibers was observed after about 45 days following nerve section. After about 145 and 245 days, however, dorsal root charge contributions had decreased significantly more than ventral root values. Exponential decay curves were fitted separately to charge data for sensory and for motor fibers. The calculated value for the endpoint of the decay was about 35% of the control value for motor fibers, and not significantly different from zero to sensory fibers. These results suggest that in response to axotomy, myelinated motor fiber diameters decline at first but later stabilize, while myelinated sensory fibers continue to decline and may atrophy completely if regeneration is prevented. Possible roles of electrical activity and of 'trophic' interactions with the periphery in the maintenance of cell properties are discussed.", "contents": "Differential atrophy of sensory and motor fibers following section of cat peripheral nerves. Differential effects of peripheral nerve section on myelinated sensory and motor fiber populations were investigated in 5 hindlimb nerves of cats. Upon electrical stimulation of each nerve, monophasic compound action potentials were recorded from the L6, L7 and S1 dorsal and ventral roots, and the impedance of each root was measured. The decline in the electrical charge computed from potentials 43 to 252 days after nerve section gave a measure of the effect of axotomy on the diameters of sensory and of motor fibers in each nerve. No significant difference in the rate of atrophy of sensory and motor fibers was observed after about 45 days following nerve section. After about 145 and 245 days, however, dorsal root charge contributions had decreased significantly more than ventral root values. Exponential decay curves were fitted separately to charge data for sensory and for motor fibers. The calculated value for the endpoint of the decay was about 35% of the control value for motor fibers, and not significantly different from zero to sensory fibers. These results suggest that in response to axotomy, myelinated motor fiber diameters decline at first but later stabilize, while myelinated sensory fibers continue to decline and may atrophy completely if regeneration is prevented. Possible roles of electrical activity and of 'trophic' interactions with the periphery in the maintenance of cell properties are discussed."}
{"id": "PMID:228794", "title": "PRL and ACTH secretion following acute heat exposure, in intact and in hypothalamic deafferentated male rats.", "content": "Adult male rats, intact or bearing complete, anterior or posterior hypothalamic deafferentiations (CHD, AHD AND PHD, respectively) were acutely exposed to environmental temperature of 36 degrees C, and serum PRL and ACTH concentrations were determined by RIA. In intact animals, heat exposure resulted in elevated serum PRL and ACTH levels. None of the deafferentations affected basal serum PRL concentrations, whereas those of ACTH were elevated in both CHD and AHD, but not in PHD groups, as compared to intact controls. The PRL heat response was completely absent in CHD, attenuated in AHD, and delayed in PHD animals, and the ACTH heat response was absent in all three groups. These results demonstrate (1) that acute exposure to elevated environmental temperature stimulates secretion of PRL and of ACTH; (2) that this stimulation is carried out by diverse neural pathways; and, (3) that hypothalamic modulation of the secretion of PRL and ACTH is effected by independent mechanisms.", "contents": "PRL and ACTH secretion following acute heat exposure, in intact and in hypothalamic deafferentated male rats. Adult male rats, intact or bearing complete, anterior or posterior hypothalamic deafferentiations (CHD, AHD AND PHD, respectively) were acutely exposed to environmental temperature of 36 degrees C, and serum PRL and ACTH concentrations were determined by RIA. In intact animals, heat exposure resulted in elevated serum PRL and ACTH levels. None of the deafferentations affected basal serum PRL concentrations, whereas those of ACTH were elevated in both CHD and AHD, but not in PHD groups, as compared to intact controls. The PRL heat response was completely absent in CHD, attenuated in AHD, and delayed in PHD animals, and the ACTH heat response was absent in all three groups. These results demonstrate (1) that acute exposure to elevated environmental temperature stimulates secretion of PRL and of ACTH; (2) that this stimulation is carried out by diverse neural pathways; and, (3) that hypothalamic modulation of the secretion of PRL and ACTH is effected by independent mechanisms."}
{"id": "PMID:228795", "title": "Estrogen-induced efflux of endogenous catecholamines from the hypothalamus in vitro.", "content": "Short-term organ cultures of the intact hypothalamus were used to study the effects of various estrogenic compounds on catecholamine release. Estradiol-17 beta (0.1--20 microM) produced a concentration-dependent efflux of norepinephrine and dopamine while its biologically inactive enantiomer, estradiol-17 alpha, was ineffective at concentrations up to 20 microM. Diethylstilbestrol, a potent non-steroidal estrogen, was as effective as estradiol-17 beta in inducing catecholamine efflux. In contrast, weakly or non-estrogenic steroids such as estrone, estriol, and corticosterone were without effect. The time course of the estrogen-induced efflux of hypothalamic catecholamines was similar to that previously reported for the estrogen-induced accumulation of hypothalamic cAMP, providing further evidence for the involvement of catecholamines in this effect. Theses results suggest that estrogen may facilitate the release of catecholamines within the hypothalamus.", "contents": "Estrogen-induced efflux of endogenous catecholamines from the hypothalamus in vitro. Short-term organ cultures of the intact hypothalamus were used to study the effects of various estrogenic compounds on catecholamine release. Estradiol-17 beta (0.1--20 microM) produced a concentration-dependent efflux of norepinephrine and dopamine while its biologically inactive enantiomer, estradiol-17 alpha, was ineffective at concentrations up to 20 microM. Diethylstilbestrol, a potent non-steroidal estrogen, was as effective as estradiol-17 beta in inducing catecholamine efflux. In contrast, weakly or non-estrogenic steroids such as estrone, estriol, and corticosterone were without effect. The time course of the estrogen-induced efflux of hypothalamic catecholamines was similar to that previously reported for the estrogen-induced accumulation of hypothalamic cAMP, providing further evidence for the involvement of catecholamines in this effect. Theses results suggest that estrogen may facilitate the release of catecholamines within the hypothalamus."}
{"id": "PMID:228796", "title": "Electric membrane properties of human DRG neurons in cell culture and the effect of high K medium.", "content": "Cell cultures were prepared from human fetal and newborn dorsal root ganglia (DRG) and maintained in culture medium with normal (4 mM) and elevated (20 mM) potassium (K). Both types of cultures were transferred to 4 mM K, and the electrical membrane properties of the DRG neurons characterized by an extensive investigation of resting membrane potential, specific membrane resistance (Rm) and capacitance, time constant (tau), rheobasic current, and various aspects of the action potential, including overshoot, duration (DT), afterhyperpolarization and absolute refractory period (ARP). No previous quantitative determinations of these membrane properties for human neurons could be found. However, our values were in good agreement with those reported for the DRG neurons of other mammalian species both in vitro and in situ. Significant correlations occurred between membrane properties and the developmental age of each specimen used for culturing. However, the data must be interpreted cautiously due to the limited number of specimens used (4) and the possibility of differential responses of the specimens to the experimental situation. Precultivation in high K medium had profound effects on both passive and active membrane properties: the primary effect being to reduce Rm, and as a result tau, DT, and ARP were also reduced. These observations add further support to the hypothesis that high K in vitro can substitute to some extent for trophic factors normally present in situ.", "contents": "Electric membrane properties of human DRG neurons in cell culture and the effect of high K medium. Cell cultures were prepared from human fetal and newborn dorsal root ganglia (DRG) and maintained in culture medium with normal (4 mM) and elevated (20 mM) potassium (K). Both types of cultures were transferred to 4 mM K, and the electrical membrane properties of the DRG neurons characterized by an extensive investigation of resting membrane potential, specific membrane resistance (Rm) and capacitance, time constant (tau), rheobasic current, and various aspects of the action potential, including overshoot, duration (DT), afterhyperpolarization and absolute refractory period (ARP). No previous quantitative determinations of these membrane properties for human neurons could be found. However, our values were in good agreement with those reported for the DRG neurons of other mammalian species both in vitro and in situ. Significant correlations occurred between membrane properties and the developmental age of each specimen used for culturing. However, the data must be interpreted cautiously due to the limited number of specimens used (4) and the possibility of differential responses of the specimens to the experimental situation. Precultivation in high K medium had profound effects on both passive and active membrane properties: the primary effect being to reduce Rm, and as a result tau, DT, and ARP were also reduced. These observations add further support to the hypothesis that high K in vitro can substitute to some extent for trophic factors normally present in situ."}
{"id": "PMID:228800", "title": "Cyclic nucleotides in the rat neostriatum: push-pull perfusion studies.", "content": "A push-pull perfusion technique was employed for in vivo study of adenosine 3',5'-monophosphate (cAMP) and guanosine 3',5'-monophosphate (cGMP) in the rat caudate nucleus. Addition of dopamine to the perfusion fluid elicited dose-dependent increases of both cAMP and cGMP perfusate concentrations. In separate experiments, it was found that pretreatment of animals with the dopamine antagonist, pimozide, significantly depressed both nucleotide responses to dopamine perfusion over the dose range studied. Mechanistic interpretations of the observations are considered. The push-pull perfusion technique appears to provide an extremely useful means of examining extracellular cyclic nucleotide levels in a discrete brain region, in vivo, under dynamic conditions.", "contents": "Cyclic nucleotides in the rat neostriatum: push-pull perfusion studies. A push-pull perfusion technique was employed for in vivo study of adenosine 3',5'-monophosphate (cAMP) and guanosine 3',5'-monophosphate (cGMP) in the rat caudate nucleus. Addition of dopamine to the perfusion fluid elicited dose-dependent increases of both cAMP and cGMP perfusate concentrations. In separate experiments, it was found that pretreatment of animals with the dopamine antagonist, pimozide, significantly depressed both nucleotide responses to dopamine perfusion over the dose range studied. Mechanistic interpretations of the observations are considered. The push-pull perfusion technique appears to provide an extremely useful means of examining extracellular cyclic nucleotide levels in a discrete brain region, in vivo, under dynamic conditions."}
{"id": "PMID:228802", "title": "The Rosenblueth phenomenon.", "content": "Rosenblueth and Luco demonstrated in 1939 that, during prolonged stimulation of a motor nerve, neuromuscular fatigue is followed by a rise of tension that has been called the Rosenblueth Phenomenon. The purpose of this work was to investigate the Rosenblueth Phenomenon in a cat neuromuscular preparation in which the nerves were severed at different levels and stimulated at 60 Hz for several hours. It was demonstrated that in the longer nerve preparation the Rosenblueth Phenomenon starts earlier and its maximal tension is higher. Acetylcholine sensitivity was studied in the superior cervical ganglion preparation and no change was observed when tested before stimulation, during fatigue, and during the Rosenblueth Phenomenon. It is concluded that the onset and amplitude of the Rosenblueth Phenomenon depend on the length of the peripheral nerve stump: the longer the stump, the earlier and higher the response. It is suggested that the Rosenblueth Phenomenon is produced by an increase in the transmitter release which would be due to axonal progression of molecules along the nerve.", "contents": "The Rosenblueth phenomenon. Rosenblueth and Luco demonstrated in 1939 that, during prolonged stimulation of a motor nerve, neuromuscular fatigue is followed by a rise of tension that has been called the Rosenblueth Phenomenon. The purpose of this work was to investigate the Rosenblueth Phenomenon in a cat neuromuscular preparation in which the nerves were severed at different levels and stimulated at 60 Hz for several hours. It was demonstrated that in the longer nerve preparation the Rosenblueth Phenomenon starts earlier and its maximal tension is higher. Acetylcholine sensitivity was studied in the superior cervical ganglion preparation and no change was observed when tested before stimulation, during fatigue, and during the Rosenblueth Phenomenon. It is concluded that the onset and amplitude of the Rosenblueth Phenomenon depend on the length of the peripheral nerve stump: the longer the stump, the earlier and higher the response. It is suggested that the Rosenblueth Phenomenon is produced by an increase in the transmitter release which would be due to axonal progression of molecules along the nerve."}
{"id": "PMID:228804", "title": "Structure and dynamics of neural network oscillators.", "content": "Techniques are given to represent oscillating neural networks by asynchronous logical switching networks, and to analyze the oscillating networks using a directed graph called a state transition diagram. Consideration is restricted to network oscillators containing no rhythm determining pacemaker neurons, and no neurons exhibiting self-limiting properties such as post-inhibitory rebound or accumulating refractoriness. In the state transition diagrams, stable oscillations are associated with a particular geometric configuration called a cyclic attractor (the heavy cycle in Fig. 2). We show that given the network connectivity it is possible to predict autonomous dynamic behaviour, as well as behaviour following hyperpolarizing or depolarizing inputs to neurons of the network. Conversely, given information about patterns of firing activity during cycles and transients of neural networks, the network connectivity can be predicted. The theoretical techniques can be used to generate a census of network structures capable of generating stable oscillations. Several representative network oscillators are discussed in the context of previous theoretical and experimental studies of the structure of neural network oscillators. Although the number of theoretically possile network oscillators capable of generating sustained oscillations is very large, the techniques which are given should be useful in the design of experiments capable of distinguishing between equally plausible hypotheses.", "contents": "Structure and dynamics of neural network oscillators. Techniques are given to represent oscillating neural networks by asynchronous logical switching networks, and to analyze the oscillating networks using a directed graph called a state transition diagram. Consideration is restricted to network oscillators containing no rhythm determining pacemaker neurons, and no neurons exhibiting self-limiting properties such as post-inhibitory rebound or accumulating refractoriness. In the state transition diagrams, stable oscillations are associated with a particular geometric configuration called a cyclic attractor (the heavy cycle in Fig. 2). We show that given the network connectivity it is possible to predict autonomous dynamic behaviour, as well as behaviour following hyperpolarizing or depolarizing inputs to neurons of the network. Conversely, given information about patterns of firing activity during cycles and transients of neural networks, the network connectivity can be predicted. The theoretical techniques can be used to generate a census of network structures capable of generating stable oscillations. Several representative network oscillators are discussed in the context of previous theoretical and experimental studies of the structure of neural network oscillators. Although the number of theoretically possile network oscillators capable of generating sustained oscillations is very large, the techniques which are given should be useful in the design of experiments capable of distinguishing between equally plausible hypotheses."}
{"id": "PMID:228803", "title": "Activity of medullary reticular formation neurons in the unrestrained cat during waking and sleep.", "content": "Single units, recorded in the medial medullary reticular formation (RF) in unrestrained, behaving cats, discharged in conjunction with specific movements and postures. Most cells were also active during REM sleep. Discharge rates in active waking and REM sleep were positively correlated and discharge patterns in these states were similar. We conclude that activity in these cells is related to the motor activation occurring in both active waking and REM sleep. We found no cells whose discharge was related in a non-specific way to motor tone or to REM sleep atonia. We discuss mechanisms by which medullary units with specific motor relations may give rise when stimulated to the relatively non-specific motor effects previously reported.", "contents": "Activity of medullary reticular formation neurons in the unrestrained cat during waking and sleep. Single units, recorded in the medial medullary reticular formation (RF) in unrestrained, behaving cats, discharged in conjunction with specific movements and postures. Most cells were also active during REM sleep. Discharge rates in active waking and REM sleep were positively correlated and discharge patterns in these states were similar. We conclude that activity in these cells is related to the motor activation occurring in both active waking and REM sleep. We found no cells whose discharge was related in a non-specific way to motor tone or to REM sleep atonia. We discuss mechanisms by which medullary units with specific motor relations may give rise when stimulated to the relatively non-specific motor effects previously reported."}
{"id": "PMID:228805", "title": "Single cell isolation: a way to examine network interactions.", "content": "A procedure for isolating identified, small neurons from snail ganglia is described. The technique allows a particular neuron, previously identified by morphological and electrophysiological characteristics, to be marked and then isolated from the ganglia. This procedure was developed to permit the detailed comparison of the electrical characteristics of a neuron before and after isolation from an intact system. An earlier description has appeared. The cell somata is marked intracellularly by the iontophoretic injection of Procion navy blue H3RS which visually differentiates the cell from other cells in the ganglion. The ganglion is then treated with a trypsin-haluronidase solution to soften the ganglion sheath, which is then removed. The cells are gently shaken to isolate them from the ganglion and then examined electrophysiologically. A comparison of membrane properties, such as action potential height, duration and rate of rise and decay was made before and after all treatments were applied to assess deleterious effect. An analysis of network properties, such as burst duration, number of spikes per burst and presynaptic activity was also performed after each phase of the procedure. No significant differences were noted after dye injection, enzyme treatment, and where appropriate, after isolation. An increase in input resistance and corresponding decrease in the slope of the steady state current--voltage plot (I--V plot) were observed after isolation of a cell. These were expected results of removing the 'load' (i.e. axon or electrical coupling) from the cell soma. This method may be applied to many other systems to study the effects of network interactions on the properties of a single cell and should therefore facilitate the analysis of neuronal networks as well as single cell properties.", "contents": "Single cell isolation: a way to examine network interactions. A procedure for isolating identified, small neurons from snail ganglia is described. The technique allows a particular neuron, previously identified by morphological and electrophysiological characteristics, to be marked and then isolated from the ganglia. This procedure was developed to permit the detailed comparison of the electrical characteristics of a neuron before and after isolation from an intact system. An earlier description has appeared. The cell somata is marked intracellularly by the iontophoretic injection of Procion navy blue H3RS which visually differentiates the cell from other cells in the ganglion. The ganglion is then treated with a trypsin-haluronidase solution to soften the ganglion sheath, which is then removed. The cells are gently shaken to isolate them from the ganglion and then examined electrophysiologically. A comparison of membrane properties, such as action potential height, duration and rate of rise and decay was made before and after all treatments were applied to assess deleterious effect. An analysis of network properties, such as burst duration, number of spikes per burst and presynaptic activity was also performed after each phase of the procedure. No significant differences were noted after dye injection, enzyme treatment, and where appropriate, after isolation. An increase in input resistance and corresponding decrease in the slope of the steady state current--voltage plot (I--V plot) were observed after isolation of a cell. These were expected results of removing the 'load' (i.e. axon or electrical coupling) from the cell soma. This method may be applied to many other systems to study the effects of network interactions on the properties of a single cell and should therefore facilitate the analysis of neuronal networks as well as single cell properties."}
{"id": "PMID:228806", "title": "A new method for receptor autoradiography: [3H]opioid receptors in rat brain.", "content": "Opioid receptors can be labeled with [3H]ligands in lightly fixed tissue sections mounted on microscope slides. The preparation of these sections does not seem to alter any of the known characteristics of opioid receptors. The light microscopic autoradiographic distribution of these binding sites can be observed if one attaches emulsion-coated coverslips to these slides to obtain autoradiograms. The distribution of [3H]diprenorphine binding sites determined by this in vitro method is identical to the distribution found in earlier studies utilizing in vivo labeling of opioid receptors. In addition, [3H]opioid peptide binding sites and [3H]dihydromorphine binding sites may be similar, perhaps identical, to those for [3H]diprenorphine, an opiate antagonist. This method has several important advantages over earlier methods for determining the autoradiographic localization of receptors. It is possible, by washing, to reduce nonspecific binding to low levels. Since receptor labeling is performed with single tissue sections mounted on slides, one can examine different receptors in different but adjacent sections. One can use ligands that are not entirely suitable for in vivo labeling (For example, one can use [3H]peptides which do not normally cross the blood-brain barrier). One can perform autoradiographic studies after labeling tissues under a wide variety of conditions (For example, one can examine the effects of various ions and nucleotides on ligand binding distributions). This technique seems to be free of various artifacts, such as edge artifacts, which were common by techniques used in our laboratory earlier. Since one does not have to load an entire animal with radioactive ligand as one must with in vivo labeling, this approach is economically advantageous. One can use postmortem tissues, including that from humans to study receptor distribution with a high anatomical resolution.", "contents": "A new method for receptor autoradiography: [3H]opioid receptors in rat brain. Opioid receptors can be labeled with [3H]ligands in lightly fixed tissue sections mounted on microscope slides. The preparation of these sections does not seem to alter any of the known characteristics of opioid receptors. The light microscopic autoradiographic distribution of these binding sites can be observed if one attaches emulsion-coated coverslips to these slides to obtain autoradiograms. The distribution of [3H]diprenorphine binding sites determined by this in vitro method is identical to the distribution found in earlier studies utilizing in vivo labeling of opioid receptors. In addition, [3H]opioid peptide binding sites and [3H]dihydromorphine binding sites may be similar, perhaps identical, to those for [3H]diprenorphine, an opiate antagonist. This method has several important advantages over earlier methods for determining the autoradiographic localization of receptors. It is possible, by washing, to reduce nonspecific binding to low levels. Since receptor labeling is performed with single tissue sections mounted on slides, one can examine different receptors in different but adjacent sections. One can use ligands that are not entirely suitable for in vivo labeling (For example, one can use [3H]peptides which do not normally cross the blood-brain barrier). One can perform autoradiographic studies after labeling tissues under a wide variety of conditions (For example, one can examine the effects of various ions and nucleotides on ligand binding distributions). This technique seems to be free of various artifacts, such as edge artifacts, which were common by techniques used in our laboratory earlier. Since one does not have to load an entire animal with radioactive ligand as one must with in vivo labeling, this approach is economically advantageous. One can use postmortem tissues, including that from humans to study receptor distribution with a high anatomical resolution."}
{"id": "PMID:228811", "title": "[Mechanism of lymphocyte activation by periodic acids. Blastogenesis and induction of immunomodulator populations].", "content": "Mild periodate treatment is mitogenic for T lymphocytes. With murine spleen cells periodate oxidation is effective between C8 and C9 on sialyl acid residues. With human blood lymphocytes this oxidation occurs between C7 and C8 of these residues. In vitro immune response is inhibited by periodate treatment. Activation of an immunosuppressive T lymphocyte population is obtained. Similar results are performed with human blood lymphocytes.", "contents": "[Mechanism of lymphocyte activation by periodic acids. Blastogenesis and induction of immunomodulator populations]. Mild periodate treatment is mitogenic for T lymphocytes. With murine spleen cells periodate oxidation is effective between C8 and C9 on sialyl acid residues. With human blood lymphocytes this oxidation occurs between C7 and C8 of these residues. In vitro immune response is inhibited by periodate treatment. Activation of an immunosuppressive T lymphocyte population is obtained. Similar results are performed with human blood lymphocytes."}
{"id": "PMID:228812", "title": "[Chromatin proteins and genetic control].", "content": "Gene expression is in great part under the control of proteins associated with DNA: histones which can be phosphorylated and acetylated, non-histone proteins which include enzymes, hormone receptors and other regulatory proteins. Phosphorylation seems to play an important role in chromatin regulation.", "contents": "[Chromatin proteins and genetic control]. Gene expression is in great part under the control of proteins associated with DNA: histones which can be phosphorylated and acetylated, non-histone proteins which include enzymes, hormone receptors and other regulatory proteins. Phosphorylation seems to play an important role in chromatin regulation."}
{"id": "PMID:228813", "title": "[Regulation of glycogen metabolism in the liver and hepatic glycogenosis due to phosphorylase system deficiency].", "content": "Glycogen synthesis and breakdown in the liver are tightly controlled through different mechanisms. The purpose of this review is to describe some properties of the enzymes involved in the glycogen metabolism and the sequence of events by which glucose, allosteric effectors and hormones control this metabolism in the liver. Clinical, genetic and biological aspects of the phosphorylase and the phosphorylase kinase deficiencies are examined. The enzymatic analysis of the haemolysates from the patients allows discrimination of these two types of glycogenosis.", "contents": "[Regulation of glycogen metabolism in the liver and hepatic glycogenosis due to phosphorylase system deficiency]. Glycogen synthesis and breakdown in the liver are tightly controlled through different mechanisms. The purpose of this review is to describe some properties of the enzymes involved in the glycogen metabolism and the sequence of events by which glucose, allosteric effectors and hormones control this metabolism in the liver. Clinical, genetic and biological aspects of the phosphorylase and the phosphorylase kinase deficiencies are examined. The enzymatic analysis of the haemolysates from the patients allows discrimination of these two types of glycogenosis."}
{"id": "PMID:228815", "title": "Analysis of paramagnetic centers in X-ray-irradiated enamel, bone, and carbonate-containing hydroxyapatite by electron spin resonance spectroscopy.", "content": "Carbonate-containing hydroxyapatite, enamel, and bone were irradiated by an X-ray and investigated between 77 degrees and 350 degrees K by means of electron spin resonance (ESR) spectroscopy. The ESR spectrum of enamel irradiated at 77 degrees K in vacuum and observed at the same temperature was almost the same as that of the carbonate-containing hydroxyapatite. The temperature dependence of signal intensities confirms a spin-energy exchange between the mineral and organic constituents in bone, but in enamel no or very little spin-energy exchange between the mineral and organic constituents. Considerable similarity among the ESR spectra of enamel, bone, and carbonate-containing apatite was obtained after X-ray irradiation in air at 300 degrees K with both an X-band and a Q-band ESR spectrometer. The Q-band spectrum can be interpreted in terms of two paramagnetic species. One is identified as a CO3(3-) anion radical which has an axial symmetry with g factors of 2.0029 and 1.9972. The other species is found to be centered at g = 2.0019.", "contents": "Analysis of paramagnetic centers in X-ray-irradiated enamel, bone, and carbonate-containing hydroxyapatite by electron spin resonance spectroscopy. Carbonate-containing hydroxyapatite, enamel, and bone were irradiated by an X-ray and investigated between 77 degrees and 350 degrees K by means of electron spin resonance (ESR) spectroscopy. The ESR spectrum of enamel irradiated at 77 degrees K in vacuum and observed at the same temperature was almost the same as that of the carbonate-containing hydroxyapatite. The temperature dependence of signal intensities confirms a spin-energy exchange between the mineral and organic constituents in bone, but in enamel no or very little spin-energy exchange between the mineral and organic constituents. Considerable similarity among the ESR spectra of enamel, bone, and carbonate-containing apatite was obtained after X-ray irradiation in air at 300 degrees K with both an X-band and a Q-band ESR spectrometer. The Q-band spectrum can be interpreted in terms of two paramagnetic species. One is identified as a CO3(3-) anion radical which has an axial symmetry with g factors of 2.0029 and 1.9972. The other species is found to be centered at g = 2.0019."}
{"id": "PMID:228816", "title": "The calciuria of increased fixed acid production in humans: evidence against a role for parathyroid hormone and 1,25(OH)2-vitamin D.", "content": "We measured mineral and acid balances, serum iPTH, urinary cAMP/creatinine, and plasma concentrations of 25OHD and 1,25(OH)2D in 7 healthy adults during control conditions and during increased fixed acid production achieved either by the administration of NH4Cl (N = 3) or by increased dietary protein intake (N = 4). When acid production was increased, the subjects were in positive acid balance and negative Ca balance because of increased urinary Ca excretion. Serum iPTH fell slightly but urinary cAMP and the plasma levels of vitamin D metabolites did not change. W conclude that the accelerated skeletal and urinary losses of Ca that occur when fixed acid production is increased are not contributed to nor compensated for by the parathyroid-vitamin D endocrine systems.", "contents": "The calciuria of increased fixed acid production in humans: evidence against a role for parathyroid hormone and 1,25(OH)2-vitamin D. We measured mineral and acid balances, serum iPTH, urinary cAMP/creatinine, and plasma concentrations of 25OHD and 1,25(OH)2D in 7 healthy adults during control conditions and during increased fixed acid production achieved either by the administration of NH4Cl (N = 3) or by increased dietary protein intake (N = 4). When acid production was increased, the subjects were in positive acid balance and negative Ca balance because of increased urinary Ca excretion. Serum iPTH fell slightly but urinary cAMP and the plasma levels of vitamin D metabolites did not change. W conclude that the accelerated skeletal and urinary losses of Ca that occur when fixed acid production is increased are not contributed to nor compensated for by the parathyroid-vitamin D endocrine systems."}
{"id": "PMID:228818", "title": "Pleomorphic C-type virus particles in bone tissue of strain 101 mice and (C3H X 101)F1 hybrids.", "content": "The proximal tibial metaphysis of apparently healthy strain 101 mice, 3-4 weeks old, and (C3H X 101)F1 hybrids, 3-48 weeks old, was studied by electron microscopy. Budding, immature, and mature (C-type virus particles were found within trabecular bone tissue of 3 of 8 strain 101 and 4 of 12 (C3H X 101)F1 mice. The particles were most common in lacunae of aging osteocytes and were only occasionally associated with osteoblasts. Although the morphology of budding and immature particles appeared to be identical with that of typical C-type viruses, most of the mature forms of particles showed atypical structure and size. The electron-dense core was very large and not clearly defined, measuring approximately 70-130 nm in diameter. This diffuse core sometimes completely filled the space within the envelope of the particles. The diameters of the pleomorphic mature C-type particles ranged from approximately 90 to 150 nm. The possible association between the production of pleomorphic C-type virus particles by bone cells and spontaneous osteomagenesis in 101 and (C3H X 101)F1 mice is discussed.", "contents": "Pleomorphic C-type virus particles in bone tissue of strain 101 mice and (C3H X 101)F1 hybrids. The proximal tibial metaphysis of apparently healthy strain 101 mice, 3-4 weeks old, and (C3H X 101)F1 hybrids, 3-48 weeks old, was studied by electron microscopy. Budding, immature, and mature (C-type virus particles were found within trabecular bone tissue of 3 of 8 strain 101 and 4 of 12 (C3H X 101)F1 mice. The particles were most common in lacunae of aging osteocytes and were only occasionally associated with osteoblasts. Although the morphology of budding and immature particles appeared to be identical with that of typical C-type viruses, most of the mature forms of particles showed atypical structure and size. The electron-dense core was very large and not clearly defined, measuring approximately 70-130 nm in diameter. This diffuse core sometimes completely filled the space within the envelope of the particles. The diameters of the pleomorphic mature C-type particles ranged from approximately 90 to 150 nm. The possible association between the production of pleomorphic C-type virus particles by bone cells and spontaneous osteomagenesis in 101 and (C3H X 101)F1 mice is discussed."}
{"id": "PMID:228821", "title": "Cortisol enhancement of PTH-stimulated cyclic AMP accumulation in cultured fetal rat long bone rudiments.", "content": "Cortisol in concentrations from 10 nM to 10 microM produced a dose-related inhibition of basal and PTH1-stimulated 45Ca and [3H]-hydroxyproline release from cultured fetal rat forelimb rudiments. PTH-stimulated cyclic AMP generation however was not diminished by cortisol; in contrast, at a concentration of 1 microM cortisol produced a 57% increase in PTH-stimulated bone cyclic AMP content. The stimulatory effect of cortisol on cyclic AMP content appeared to be the result of reduced phosphodiesterase activity, since this effect was not seen in the presence of 10 mM theophylline. It is concluded that cortisol inhibition of PTH-induced resorption in long bones is not accompanied by reduced cyclic AMP generation.", "contents": "Cortisol enhancement of PTH-stimulated cyclic AMP accumulation in cultured fetal rat long bone rudiments. Cortisol in concentrations from 10 nM to 10 microM produced a dose-related inhibition of basal and PTH1-stimulated 45Ca and [3H]-hydroxyproline release from cultured fetal rat forelimb rudiments. PTH-stimulated cyclic AMP generation however was not diminished by cortisol; in contrast, at a concentration of 1 microM cortisol produced a 57% increase in PTH-stimulated bone cyclic AMP content. The stimulatory effect of cortisol on cyclic AMP content appeared to be the result of reduced phosphodiesterase activity, since this effect was not seen in the presence of 10 mM theophylline. It is concluded that cortisol inhibition of PTH-induced resorption in long bones is not accompanied by reduced cyclic AMP generation."}
{"id": "PMID:228822", "title": "Long-term culture of cells from bone affected by Paget's disease.", "content": "Cells obtained from surgical bone specimens of eight patients with Paget's disease of bone were maintained in culture for up to 8 months and seven passages. The doubling time during the period of maximal cell growth ranged from 4 to 12 days. Evidence consistent with the hypothesis that many of the cells were bone cells included the following: (a) histochemical techniques demonstrated staining of some cells for alkaline phosphatase or acid phosphatase and succinic dehydrogenase; (b) parathyroid extract stimulated increased uptake of 3H-thymidine and 3H-uridine; (c) parathyroid extract suppressed and salmon calcitonin stimulated uptake of 3H-proline; and (d) crystalline calcium deposits were found within cells and extracellularly. Ultrastructural analysis revealed that three of the eight cultures contained cells whose nuclei had inclusions which were almost identical to those found in the osteoclast nuclei of all patients with Paget's disease. The maintenance of cells derived from pagetic bone in long-term culture should aid in testing the hypothesis that Paget's disease represents a slow virus infection of bone.", "contents": "Long-term culture of cells from bone affected by Paget's disease. Cells obtained from surgical bone specimens of eight patients with Paget's disease of bone were maintained in culture for up to 8 months and seven passages. The doubling time during the period of maximal cell growth ranged from 4 to 12 days. Evidence consistent with the hypothesis that many of the cells were bone cells included the following: (a) histochemical techniques demonstrated staining of some cells for alkaline phosphatase or acid phosphatase and succinic dehydrogenase; (b) parathyroid extract stimulated increased uptake of 3H-thymidine and 3H-uridine; (c) parathyroid extract suppressed and salmon calcitonin stimulated uptake of 3H-proline; and (d) crystalline calcium deposits were found within cells and extracellularly. Ultrastructural analysis revealed that three of the eight cultures contained cells whose nuclei had inclusions which were almost identical to those found in the osteoclast nuclei of all patients with Paget's disease. The maintenance of cells derived from pagetic bone in long-term culture should aid in testing the hypothesis that Paget's disease represents a slow virus infection of bone."}
{"id": "PMID:228823", "title": "Study of an asymmetric ESR signal in x-irradiated human tooth enamel.", "content": "An asymmetric ESR signal and an outer doublet signal centered at g = 2.00 produced in human tooth enamel by X-irradiation have been studied over a temperature range from liquid helium temperature to 380 degrees K. The line shape of the asymmetric signal for an enamel crystallite is Lorentzian at room temperature. The temperature dependence of the integrated intensity of the asymmetric signal suggests that the signal follows a singlet-triplet model with the exchange interaction of 0.022 eV. Below about 60 degrees K the asymmetric signal becomes broad as the temperature is decreased. The ENDOR line of the asymmetric signal shows that there exists interaction between the centers and protons. The temperature dependence of the integrated intensity of the double signal is analogous to that of the asymmetric signal.", "contents": "Study of an asymmetric ESR signal in x-irradiated human tooth enamel. An asymmetric ESR signal and an outer doublet signal centered at g = 2.00 produced in human tooth enamel by X-irradiation have been studied over a temperature range from liquid helium temperature to 380 degrees K. The line shape of the asymmetric signal for an enamel crystallite is Lorentzian at room temperature. The temperature dependence of the integrated intensity of the asymmetric signal suggests that the signal follows a singlet-triplet model with the exchange interaction of 0.022 eV. Below about 60 degrees K the asymmetric signal becomes broad as the temperature is decreased. The ENDOR line of the asymmetric signal shows that there exists interaction between the centers and protons. The temperature dependence of the integrated intensity of the double signal is analogous to that of the asymmetric signal."}
{"id": "PMID:228824", "title": "From beta-lipotropin to beta-endorphin and 'pro-opio-melanocortin'.", "content": "Studies on the biosynthesis of beta-LPH on the one hand, and of ACTH on the other, have produced a new concept, that of a single precursor form which contains three active molecules. Thus, it is proper to name such a precursor 'pro-opio-melanocortin.' The concept that beta-LPH was a precursor molecule was first put forward in 1967 and was based on both structural forms and biological activities. The discovery that morphine-like substances are part of the C-terminal fragment of beta-LPH brought an additional important biological side product. That, together with the recent demonstration of ACTH as part of a still larger precursor, constitutes an exciting model for the study of peptide hormone biosynthesis. We have shown unambiguously that beta-endorphin is the result of a maturation process from the large precursor, while beta-LPH is an important and transient intermediary. Since it is also present in the brain, our recent results using pars intermedia cells can be applied to study the fabrication and degradation of these molecules in the brain. We expect to see it established that all other neuropeptides are also biosynthesized as larger precursor molecules whose structure at the site of cleavage could well be constituted of two basic amino acids like in the pro-opio-melanocortin.", "contents": "From beta-lipotropin to beta-endorphin and 'pro-opio-melanocortin'. Studies on the biosynthesis of beta-LPH on the one hand, and of ACTH on the other, have produced a new concept, that of a single precursor form which contains three active molecules. Thus, it is proper to name such a precursor 'pro-opio-melanocortin.' The concept that beta-LPH was a precursor molecule was first put forward in 1967 and was based on both structural forms and biological activities. The discovery that morphine-like substances are part of the C-terminal fragment of beta-LPH brought an additional important biological side product. That, together with the recent demonstration of ACTH as part of a still larger precursor, constitutes an exciting model for the study of peptide hormone biosynthesis. We have shown unambiguously that beta-endorphin is the result of a maturation process from the large precursor, while beta-LPH is an important and transient intermediary. Since it is also present in the brain, our recent results using pars intermedia cells can be applied to study the fabrication and degradation of these molecules in the brain. We expect to see it established that all other neuropeptides are also biosynthesized as larger precursor molecules whose structure at the site of cleavage could well be constituted of two basic amino acids like in the pro-opio-melanocortin."}
{"id": "PMID:228826", "title": "Enzymatic modifications of bovine adrenocortical angiotensin II receptors.", "content": "Several classes of proteolytic enzymes were used to gain an insight into the biochemical composition of the antiotensin II (ATII) receptor prepared from bovine adrenal cortices. Exposure of the receptor fractions to trypsin reduced their capacity to bind [3H]ATII. Phospholipases A2 and C similarly inhibited the [3H]ATII binding process, while phospholipase D had no effect. Binding was stimulated following addition of phosphatidylcholine but inhibited by lysophosphatidylcholine. Neuraminidase had no influence on [3H]ATII affinity for binding, while beta-galactosidase reduced binding of the radioligand. Concanavalin A did not displace [3H]ATII bound to receptor fractions. Very little aminopeptidase activity was detected in the receptor fraction, relative to the homogenate. The data suggest that the ATII recognition sites contain protein moieties, while phospholipids may play an essential role in ATII binding. Galactose units may form a part of the ATII receptor not directly associated with the binding site. The peptidase studies indicate that ATII probably cannot be hydrolyzed to its des-Asp1 metabolite at or near the site of binding.", "contents": "Enzymatic modifications of bovine adrenocortical angiotensin II receptors. Several classes of proteolytic enzymes were used to gain an insight into the biochemical composition of the antiotensin II (ATII) receptor prepared from bovine adrenal cortices. Exposure of the receptor fractions to trypsin reduced their capacity to bind [3H]ATII. Phospholipases A2 and C similarly inhibited the [3H]ATII binding process, while phospholipase D had no effect. Binding was stimulated following addition of phosphatidylcholine but inhibited by lysophosphatidylcholine. Neuraminidase had no influence on [3H]ATII affinity for binding, while beta-galactosidase reduced binding of the radioligand. Concanavalin A did not displace [3H]ATII bound to receptor fractions. Very little aminopeptidase activity was detected in the receptor fraction, relative to the homogenate. The data suggest that the ATII recognition sites contain protein moieties, while phospholipids may play an essential role in ATII binding. Galactose units may form a part of the ATII receptor not directly associated with the binding site. The peptidase studies indicate that ATII probably cannot be hydrolyzed to its des-Asp1 metabolite at or near the site of binding."}
{"id": "PMID:228828", "title": "Evidence for two adenine derivative receptors in rat ileum which are not involved in the nonadrenergic, noncholinergic response.", "content": "The receptors mediating inhibition of the rat ileum by adenosine and adenine nucleotides were studied. ATP and ADP were more potent than AMP or adeonsine. Theophylline antagonized the effects of adenosine and AMP but not those of ATP or ADP. Preparations desensitized to ATP or ADP were still inhibited by adenosine and vice versa. The nonadrenergic, noncholinergic inhibition produced by field stimulation or nicotine was not attenuated by the presence of theophylline or desensitization to ATP. These data indicate that more than one adenine derivative receptor is present in rat ileum and that ATP and adenosine are unlikely candidates for the unknown transmitter.", "contents": "Evidence for two adenine derivative receptors in rat ileum which are not involved in the nonadrenergic, noncholinergic response. The receptors mediating inhibition of the rat ileum by adenosine and adenine nucleotides were studied. ATP and ADP were more potent than AMP or adeonsine. Theophylline antagonized the effects of adenosine and AMP but not those of ATP or ADP. Preparations desensitized to ATP or ADP were still inhibited by adenosine and vice versa. The nonadrenergic, noncholinergic inhibition produced by field stimulation or nicotine was not attenuated by the presence of theophylline or desensitization to ATP. These data indicate that more than one adenine derivative receptor is present in rat ileum and that ATP and adenosine are unlikely candidates for the unknown transmitter."}
{"id": "PMID:228829", "title": "An opiate receptor on frog sciatic nerve axons.", "content": "The effect of meperidine (3 X 10(4) M) on the action potential of frog sciatic nerve was examined by means of the double sucrose gap technique. Meperidine decreased the amplitude, maximum rate of depolarization, and maximum rate of repolarization of the action potential but had no effect on the resting potential. This depression in amplitude and maximum rate of rise was partially blocked by naloxone (1 X 10(-8) M) while the maximum rate of depolarization was further depressed. The data suggest that the effect of meperidine is due to two mechanisms, a nonspecific local anaesthetic like effect and an opiate receptor mediated effect.", "contents": "An opiate receptor on frog sciatic nerve axons. The effect of meperidine (3 X 10(4) M) on the action potential of frog sciatic nerve was examined by means of the double sucrose gap technique. Meperidine decreased the amplitude, maximum rate of depolarization, and maximum rate of repolarization of the action potential but had no effect on the resting potential. This depression in amplitude and maximum rate of rise was partially blocked by naloxone (1 X 10(-8) M) while the maximum rate of depolarization was further depressed. The data suggest that the effect of meperidine is due to two mechanisms, a nonspecific local anaesthetic like effect and an opiate receptor mediated effect."}
{"id": "PMID:228830", "title": "Mg2+--Ca2+--Na+ interactions in uterine smooth muscle: studies with cAMP.", "content": "The influence of variation in the extracellular concentrations of Na+, Mg2+, and Ca2+ in the depolarizing medium on isoproterenol-induced increases in cAMP levels and relaxation was studied in rat uterus. Isoproterenol (10(-8) M) failed to increase cAMP levels in the high-K+ medium containing no Na+. When 80 mM Na+ was present in the medium, isoproterenol caused increases in cAMP levels similar to those observed in nondepolarized uterus. A similar effect of 2.5 mM Mg2+ was observed on the cAMP response. These effects of Na+ and Mg2+ were antagonized by increasing the extracellular concentration of Ca2+. The simultaneous presence of 80 mM Na+ and 2.5 mM Mg2+ did not produce an additive effect on the cAMP responses.", "contents": "Mg2+--Ca2+--Na+ interactions in uterine smooth muscle: studies with cAMP. The influence of variation in the extracellular concentrations of Na+, Mg2+, and Ca2+ in the depolarizing medium on isoproterenol-induced increases in cAMP levels and relaxation was studied in rat uterus. Isoproterenol (10(-8) M) failed to increase cAMP levels in the high-K+ medium containing no Na+. When 80 mM Na+ was present in the medium, isoproterenol caused increases in cAMP levels similar to those observed in nondepolarized uterus. A similar effect of 2.5 mM Mg2+ was observed on the cAMP response. These effects of Na+ and Mg2+ were antagonized by increasing the extracellular concentration of Ca2+. The simultaneous presence of 80 mM Na+ and 2.5 mM Mg2+ did not produce an additive effect on the cAMP responses."}
{"id": "PMID:228831", "title": "Interferon, antibody responses and protection induced by an intranasal infectious bovine rhinotracheitis vaccine.", "content": "The interferon and antibody response induced by an intranasal infectious bovine rhinotracheitis vaccine was followed in 22 calves over a nine month period and the ability of these vaccinated calves to withstand challenge with virulent infectious bovine rhinotracheitis virus was assessed. Interferon was detected two to three days post-vaccination and disappeared by the tenth day. Nasal and serum antibodies appeared by day 7 and persisted for nine months. The calves challenged three days postvaccination came down with disease typical of infectious bovine rhinotracheitis, whereas calves challenged three weeks, three months or nine months postvaccination resisted infection.", "contents": "Interferon, antibody responses and protection induced by an intranasal infectious bovine rhinotracheitis vaccine. The interferon and antibody response induced by an intranasal infectious bovine rhinotracheitis vaccine was followed in 22 calves over a nine month period and the ability of these vaccinated calves to withstand challenge with virulent infectious bovine rhinotracheitis virus was assessed. Interferon was detected two to three days post-vaccination and disappeared by the tenth day. Nasal and serum antibodies appeared by day 7 and persisted for nine months. The calves challenged three days postvaccination came down with disease typical of infectious bovine rhinotracheitis, whereas calves challenged three weeks, three months or nine months postvaccination resisted infection."}
{"id": "PMID:228832", "title": "Neurologic involvement in glucagonoma syndrome: response to combination chemotherapy with 5-fluorouracil and streptozotocin.", "content": "A 34-year-old man presented with classic glucagonoma syndrome manifested by weight loss, dermatitis, stomatitis, anemia, and mild diabetes mellitus. The diagnosis of glucagonoma was made by light and electron microscopic demonstration of a metastatic alpha cell carcinoma in a liver biopsy specimen. Plasma glucagon concentration was abnormally high. The patient also had symptoms and signs of involvement of the central nervous system. Radionuclide and CAT scans of the brain, negative CSF cytology and myelography excluded the possibility of metastases or other space-occupying lesions. Glucagon was demonstrated in the CSF. We postulate that the neurologic symptoms were due to direct or indirect effect of this hormone on the brain. Following therapy with streptozotocin and 5-fluorouracil, the patient had a subjective and objective clinical and hormonal remission of his disease including amelioration of his neurological impairment.", "contents": "Neurologic involvement in glucagonoma syndrome: response to combination chemotherapy with 5-fluorouracil and streptozotocin. A 34-year-old man presented with classic glucagonoma syndrome manifested by weight loss, dermatitis, stomatitis, anemia, and mild diabetes mellitus. The diagnosis of glucagonoma was made by light and electron microscopic demonstration of a metastatic alpha cell carcinoma in a liver biopsy specimen. Plasma glucagon concentration was abnormally high. The patient also had symptoms and signs of involvement of the central nervous system. Radionuclide and CAT scans of the brain, negative CSF cytology and myelography excluded the possibility of metastases or other space-occupying lesions. Glucagon was demonstrated in the CSF. We postulate that the neurologic symptoms were due to direct or indirect effect of this hormone on the brain. Following therapy with streptozotocin and 5-fluorouracil, the patient had a subjective and objective clinical and hormonal remission of his disease including amelioration of his neurological impairment."}
{"id": "PMID:228833", "title": "Peripheral neuropathy associated with cis-dichlorodiammineplatinum (II) treatment.", "content": "Peripheral neuropathy developed in two cases of recurrent bladder carcinoma treated with Cis-dichlorodiammineplatinum (II) (DDP) at a dose of 75 mg/m2 IV every 3 weeks. The neuropathy appeared in both patients while they were achieving a subjective and objective response to DDP. The neuropathy was reversible in one patient. In the other patient, a disabling sensory neuropathy progressed despite cessation of therapy. The temporal relationship between the neurological symptoms and the administration of DDP implicate this drug as the possible causative agent in the peripheral neuropathy.", "contents": "Peripheral neuropathy associated with cis-dichlorodiammineplatinum (II) treatment. Peripheral neuropathy developed in two cases of recurrent bladder carcinoma treated with Cis-dichlorodiammineplatinum (II) (DDP) at a dose of 75 mg/m2 IV every 3 weeks. The neuropathy appeared in both patients while they were achieving a subjective and objective response to DDP. The neuropathy was reversible in one patient. In the other patient, a disabling sensory neuropathy progressed despite cessation of therapy. The temporal relationship between the neurological symptoms and the administration of DDP implicate this drug as the possible causative agent in the peripheral neuropathy."}
{"id": "PMID:228834", "title": "The relation between Epstein-Barr virus antibodies and clinical symptomatology and immunodeficiency in patients with Hodgkin's disease.", "content": "Anti-Epstein-Barr virus (EBV) titers were measured in the sera of 37 patients with Hodgkin's disease and in 40 normal controls. The patients were grouped according to histologic type, clinical symptomatology (relapse or remission), and their immune state (immunodeficient or non-immunodeficient). Anti-Epstein-Barr nuclear antigens (EBNA) and antiviral capside antigens (VCA) titers were higher in patients with Hodgkin's disease than in the controls. Anti-EBNA titers were significantly higher in patients with lymphocyte predominance, and anti-VCA titers were significantly higher in patients with mixed cellularity. Patients in clinical relapse had higher anti-EBV antibody titers than patients in remission or those in the control group. Immunodeficent pateints had significantly higher anti-VCA titers than either the non-immuno-deficient or the control cases. We believe high anti-EBV titers are related to immunodeficiencies. The relationship between Hodgkin's disease and EBV is discussed.", "contents": "The relation between Epstein-Barr virus antibodies and clinical symptomatology and immunodeficiency in patients with Hodgkin's disease. Anti-Epstein-Barr virus (EBV) titers were measured in the sera of 37 patients with Hodgkin's disease and in 40 normal controls. The patients were grouped according to histologic type, clinical symptomatology (relapse or remission), and their immune state (immunodeficient or non-immunodeficient). Anti-Epstein-Barr nuclear antigens (EBNA) and antiviral capside antigens (VCA) titers were higher in patients with Hodgkin's disease than in the controls. Anti-EBNA titers were significantly higher in patients with lymphocyte predominance, and anti-VCA titers were significantly higher in patients with mixed cellularity. Patients in clinical relapse had higher anti-EBV antibody titers than patients in remission or those in the control group. Immunodeficent pateints had significantly higher anti-VCA titers than either the non-immuno-deficient or the control cases. We believe high anti-EBV titers are related to immunodeficiencies. The relationship between Hodgkin's disease and EBV is discussed."}
{"id": "PMID:228836", "title": "Angiomatoid malignant fibrous histiocytoma: a distinct fibrohistiocytic tumor of children and young adults simulating a vascular neoplasm.", "content": "This article describes 41 examples of an unusual fibrohistiocytic sarcoma which occurred primarily in the extremities of young individuals between the ages of 5 and 25 years (median 13 years). It manifested as a nodular subcutaneous growth that seldom caused tenderness or pain, and clinically was often mistaken for a hematoma or a hemangioma. Grossly, the tumor presented as a circumscribed, multinodular or multicystic, hemorrhagic mass that ranged in size from 0.7 to 10 cm (median 2.5 cm). On microscopic examination, it consisted principally of 1) solid arrays or nests of fibroblast- and histiocyte-like cells, not infrequently containing varying amounts of intracellular hemosiderin or lipid, 2) focal areas of hemorrhage or hemorrhagic cyst-like spaces, sometimes occupying the major portion of the tumor, and 3) aggregates of chronic inflammatory cells, chiefly lymphocytes and plasmacytes, a feature that caused confusion with a lymph node metastasis in several cases. Follow-up information, available in 24 patients, revealed a variable clinical course. Twenty-one patients were alive, 11 with recurrence (including one with 9 recurrences in a 21-year period) one with recurrence and metastasis and one with metastasis. Three patients had died of metastasis 1, 3, and 13 years respectively, after the initial surgical therapy. The exact histogenesis is still obscure. Most likely it is a tumor of fibroblast- and histiocyte-like cells, akin to malignant fibrous histiocytoma, but different in its age incidence, microscopic appearance and behavior.", "contents": "Angiomatoid malignant fibrous histiocytoma: a distinct fibrohistiocytic tumor of children and young adults simulating a vascular neoplasm. This article describes 41 examples of an unusual fibrohistiocytic sarcoma which occurred primarily in the extremities of young individuals between the ages of 5 and 25 years (median 13 years). It manifested as a nodular subcutaneous growth that seldom caused tenderness or pain, and clinically was often mistaken for a hematoma or a hemangioma. Grossly, the tumor presented as a circumscribed, multinodular or multicystic, hemorrhagic mass that ranged in size from 0.7 to 10 cm (median 2.5 cm). On microscopic examination, it consisted principally of 1) solid arrays or nests of fibroblast- and histiocyte-like cells, not infrequently containing varying amounts of intracellular hemosiderin or lipid, 2) focal areas of hemorrhage or hemorrhagic cyst-like spaces, sometimes occupying the major portion of the tumor, and 3) aggregates of chronic inflammatory cells, chiefly lymphocytes and plasmacytes, a feature that caused confusion with a lymph node metastasis in several cases. Follow-up information, available in 24 patients, revealed a variable clinical course. Twenty-one patients were alive, 11 with recurrence (including one with 9 recurrences in a 21-year period) one with recurrence and metastasis and one with metastasis. Three patients had died of metastasis 1, 3, and 13 years respectively, after the initial surgical therapy. The exact histogenesis is still obscure. Most likely it is a tumor of fibroblast- and histiocyte-like cells, akin to malignant fibrous histiocytoma, but different in its age incidence, microscopic appearance and behavior."}
{"id": "PMID:228837", "title": "Mixed malignant mesenchymal tumor of the cerebellar vermis.", "content": "In an example of mixed malignant mesenchymal tumor of the cerebellar vermis, striking osteoblastic differentiation was present along with extensive intradural spinal invasion. The CNS sarcomas and their variants are discussed as well as the extraskeletal osteosarcomas. Comparison is made to the teratoid tumors and other mixed and unusual posterior fossa tumor elements, and the capability of midline posterior fossa tissues for multipotential differentiation is considered.", "contents": "Mixed malignant mesenchymal tumor of the cerebellar vermis. In an example of mixed malignant mesenchymal tumor of the cerebellar vermis, striking osteoblastic differentiation was present along with extensive intradural spinal invasion. The CNS sarcomas and their variants are discussed as well as the extraskeletal osteosarcomas. Comparison is made to the teratoid tumors and other mixed and unusual posterior fossa tumor elements, and the capability of midline posterior fossa tissues for multipotential differentiation is considered."}
{"id": "PMID:228838", "title": "Ultrastructural comparison of hepatoblastoma and hepatocellular carcinoma.", "content": "The ultrastructural characteristics of fetal liver, two hepatoblastomas and two hepatocellular carcinomas were compared. Tumor cells of hepatoblastoma disclosed monotonous nuclei, poorly-developed cytoplasmic membrane system, abundant free ribosomes and prominent glycogen granules. Thos of hepatocellular carcinoma revealed comparatively pleomorphic nuclei, well-developed cytoplasmic membrane system, a few free ribosomes and numerous glycogen granules. Fetal liver showed monotonous nuclei, well-developed RER abundant free ribosomes and prominent glycogen granules. Young mesenchymal cells with well-developed RER and continuous basal lamina surrounding the epithelial cells were detected in both cases of hepatoblastoma but not in those of hepatocellular carcinoma. Tumor cells of hepatoblastoma in a case showed intramitochondrial crystalloids and thick bundles of fibrils in the cytoplasm.", "contents": "Ultrastructural comparison of hepatoblastoma and hepatocellular carcinoma. The ultrastructural characteristics of fetal liver, two hepatoblastomas and two hepatocellular carcinomas were compared. Tumor cells of hepatoblastoma disclosed monotonous nuclei, poorly-developed cytoplasmic membrane system, abundant free ribosomes and prominent glycogen granules. Thos of hepatocellular carcinoma revealed comparatively pleomorphic nuclei, well-developed cytoplasmic membrane system, a few free ribosomes and numerous glycogen granules. Fetal liver showed monotonous nuclei, well-developed RER abundant free ribosomes and prominent glycogen granules. Young mesenchymal cells with well-developed RER and continuous basal lamina surrounding the epithelial cells were detected in both cases of hepatoblastoma but not in those of hepatocellular carcinoma. Tumor cells of hepatoblastoma in a case showed intramitochondrial crystalloids and thick bundles of fibrils in the cytoplasm."}
{"id": "PMID:228839", "title": "Ovarian low-grade stromal sarcoma with thecomatous features: a critical reappraisal of the so-called \"malignant thecoma\".", "content": "A case of low-grade ovarian stromal sarcoma in a postmenopausal woman is described. Although pelvic recurrences of the tumor followed 5 and 7 years after the original surgery, the patient has remained well and without evidence of tumor 3 years since the last operation. Histopathologic, electronmicroscopic, and hormonal studies are described. There was evidence of estrogenic stimulation by the theca elements of the tumor in this patient. Cases previously reported in the world literature as malignant thecoma were analyzed, and most of them were considered inadequately documented; indeed most of them were probably either sarcomatoid granulosa cell tumors, stromal sarcomas, or fibrosarcomas. If a thecoma ever becomes malignant, the tumor cells dedifferentiate so that they cannot be recognized any longer as theca cells; instead, they proliferate as a stromal sarcoma or fibrosarcoma. It is proposed, therefore, that the term \"malignant thecoma\" not be used. On the other hand, very rare malignant ovarian stromal tumors do exist, consisting of undifferentiated stromal cells, fibroblasts, and theca cells, which can show evidence of hormonal activity.", "contents": "Ovarian low-grade stromal sarcoma with thecomatous features: a critical reappraisal of the so-called \"malignant thecoma\". A case of low-grade ovarian stromal sarcoma in a postmenopausal woman is described. Although pelvic recurrences of the tumor followed 5 and 7 years after the original surgery, the patient has remained well and without evidence of tumor 3 years since the last operation. Histopathologic, electronmicroscopic, and hormonal studies are described. There was evidence of estrogenic stimulation by the theca elements of the tumor in this patient. Cases previously reported in the world literature as malignant thecoma were analyzed, and most of them were considered inadequately documented; indeed most of them were probably either sarcomatoid granulosa cell tumors, stromal sarcomas, or fibrosarcomas. If a thecoma ever becomes malignant, the tumor cells dedifferentiate so that they cannot be recognized any longer as theca cells; instead, they proliferate as a stromal sarcoma or fibrosarcoma. It is proposed, therefore, that the term \"malignant thecoma\" not be used. On the other hand, very rare malignant ovarian stromal tumors do exist, consisting of undifferentiated stromal cells, fibroblasts, and theca cells, which can show evidence of hormonal activity."}
{"id": "PMID:228840", "title": "Acquired myeloperoxidase deficiency and recurrent infections in a patient with acute myelomonocytic leukemia.", "content": "Acquired myeloperoxidase deficiency has been reported in several hematological malignancies. The clinical course of a patient with acute myelomonocytic leukemia is described which was characterized by staphylococcal infections prior to therapy and again during a period of relapse. Neutropenia was not a feature of these two periods but in vitro studies revealed decreased bacterial killing capacity and decreased neutrophil myeloperoxidase activity. Infectious complications were not observed during drug-induced remission when bacterial killing capacity and myeloperoxidase activity were improved toward normal. These observations suggest that the myeloperoxidase deficient neutrophils were derived from leukemic progenitors.", "contents": "Acquired myeloperoxidase deficiency and recurrent infections in a patient with acute myelomonocytic leukemia. Acquired myeloperoxidase deficiency has been reported in several hematological malignancies. The clinical course of a patient with acute myelomonocytic leukemia is described which was characterized by staphylococcal infections prior to therapy and again during a period of relapse. Neutropenia was not a feature of these two periods but in vitro studies revealed decreased bacterial killing capacity and decreased neutrophil myeloperoxidase activity. Infectious complications were not observed during drug-induced remission when bacterial killing capacity and myeloperoxidase activity were improved toward normal. These observations suggest that the myeloperoxidase deficient neutrophils were derived from leukemic progenitors."}
{"id": "PMID:228841", "title": "Benign mixed tumor of the trachea.", "content": "A case of mixed tumor, salivary gland type, removed by segmental resection of the trachea is reported. Only thirteen acceptable and five probable tracheal mixed tumors have been found in the world literature. The behavior of this variety of tumor in the trachea appears to be similar to its counterpart in other sites and distinctly different from the more frequently encountered epithelial tumors: squamous cell carcinoma and adenoid cystic carcinoma.", "contents": "Benign mixed tumor of the trachea. A case of mixed tumor, salivary gland type, removed by segmental resection of the trachea is reported. Only thirteen acceptable and five probable tracheal mixed tumors have been found in the world literature. The behavior of this variety of tumor in the trachea appears to be similar to its counterpart in other sites and distinctly different from the more frequently encountered epithelial tumors: squamous cell carcinoma and adenoid cystic carcinoma."}
{"id": "PMID:228842", "title": "Urinary hexosaminidase in patients with lung carcinoma.", "content": "The specific activity of urinary hexosaminidase was determined in 58 patients with various histological types of lung carcinoma. Compared to an apparently healthy control population, 32/35 patients with widely disseminated disease showed elevated values and 18/23 patients with disease confined to the chest had normal hexosaminidase values. Detailed studies of 18 patients indicated that declining hexosaminidase values were associated with effective therapy, rising values generally accompanied progressive disease.", "contents": "Urinary hexosaminidase in patients with lung carcinoma. The specific activity of urinary hexosaminidase was determined in 58 patients with various histological types of lung carcinoma. Compared to an apparently healthy control population, 32/35 patients with widely disseminated disease showed elevated values and 18/23 patients with disease confined to the chest had normal hexosaminidase values. Detailed studies of 18 patients indicated that declining hexosaminidase values were associated with effective therapy, rising values generally accompanied progressive disease."}
{"id": "PMID:228843", "title": "Evidence for clustering of hepatitis B virus infection in families of patients with primary hepatocellular carcinoma.", "content": "Family member of 13 patients with hepatitis B surface antigen (HBsAg) positive primary hepatocellular carcinoma (PHC) were tested for the presence of hepatitis B virus-associated antigens and antibodies. Of the 122 members examined, circulating HGsAg was detected in 47 (39%), antibody to HBsAg (anti-HBs) was found in 37 (30%), and antibody to hepatitis B core antigen (anti-HBc) alone was present in 13 (11%). The relatives with the highest frequency of HBsAg positivity were the offspring of the propositus, followed by the nieces and nephews and the grandchildren. Anti-HBs and anti-HBc were detected most often in the spouses and non-blood relatives. Evidence for past and present hepatitis B virus (HBV) infection was more frequently found in the Asian family members when compared to the non-Asians. The e antigen (HBeAg) was present in 38% of the HBsAg positive individuals, including four with PHC; antibody to HBcAg (anti-HBe) was rarely detected. These results indicate that clustering of HBV infection was commonly present in family members of patients with PHC. The HBsAg positive individuals may be major contributors to the endemic pool of the virus, and may themselves be potential cases of chronic active type B hepatitis, cirrhosis, and PHC.", "contents": "Evidence for clustering of hepatitis B virus infection in families of patients with primary hepatocellular carcinoma. Family member of 13 patients with hepatitis B surface antigen (HBsAg) positive primary hepatocellular carcinoma (PHC) were tested for the presence of hepatitis B virus-associated antigens and antibodies. Of the 122 members examined, circulating HGsAg was detected in 47 (39%), antibody to HBsAg (anti-HBs) was found in 37 (30%), and antibody to hepatitis B core antigen (anti-HBc) alone was present in 13 (11%). The relatives with the highest frequency of HBsAg positivity were the offspring of the propositus, followed by the nieces and nephews and the grandchildren. Anti-HBs and anti-HBc were detected most often in the spouses and non-blood relatives. Evidence for past and present hepatitis B virus (HBV) infection was more frequently found in the Asian family members when compared to the non-Asians. The e antigen (HBeAg) was present in 38% of the HBsAg positive individuals, including four with PHC; antibody to HBcAg (anti-HBe) was rarely detected. These results indicate that clustering of HBV infection was commonly present in family members of patients with PHC. The HBsAg positive individuals may be major contributors to the endemic pool of the virus, and may themselves be potential cases of chronic active type B hepatitis, cirrhosis, and PHC."}
{"id": "PMID:228844", "title": "Neurological complications of malignant germ cell tumors of testis: biology of brain metastases (I).", "content": "Central nervous system metastases are a common complication of disseminated germ cell tumors of the testis. They occurred in 16% of 242 patients treated and in 25% of the patients who died in our VAB chemotherapy series. Pulmonary metastases preceded or coincided with the development of brain metastases. The frequency of brain metastases differed with the histology of the primary tumor. They occurred in 13% of pure embryonal carcinomas, 18% of mixed tumors containing embryonal or choriocarcinoma elements, and 83% of pure choriocarcinomas. Embryonal carcinoma and choriocarcinoma were the principle histologies found in brain metastases. Characteristically, pure choriocarcinoma deposits in the brain were multiple (8/9) and cerebellar involvement was common (5/9). Pure embryonal carcinoma CNS metastases were typically single (6/8) or very few and cerebellar involvement was not observed. The interval from the diagnosis of malignancy to the diagnosis of brain metastases was longer for embryonal carcinoma than for pure choriocarcinoma (23 mos. vs. 6.5 mos.). Survival following the diagnosis of brain metastases was poor. There was a tendency toward longer survival for histologically pure embryonal carcinoma deposits in the brain than for the pure choriocarcinomas (6.5 mos. vs. 1 mo.).", "contents": "Neurological complications of malignant germ cell tumors of testis: biology of brain metastases (I). Central nervous system metastases are a common complication of disseminated germ cell tumors of the testis. They occurred in 16% of 242 patients treated and in 25% of the patients who died in our VAB chemotherapy series. Pulmonary metastases preceded or coincided with the development of brain metastases. The frequency of brain metastases differed with the histology of the primary tumor. They occurred in 13% of pure embryonal carcinomas, 18% of mixed tumors containing embryonal or choriocarcinoma elements, and 83% of pure choriocarcinomas. Embryonal carcinoma and choriocarcinoma were the principle histologies found in brain metastases. Characteristically, pure choriocarcinoma deposits in the brain were multiple (8/9) and cerebellar involvement was common (5/9). Pure embryonal carcinoma CNS metastases were typically single (6/8) or very few and cerebellar involvement was not observed. The interval from the diagnosis of malignancy to the diagnosis of brain metastases was longer for embryonal carcinoma than for pure choriocarcinoma (23 mos. vs. 6.5 mos.). Survival following the diagnosis of brain metastases was poor. There was a tendency toward longer survival for histologically pure embryonal carcinoma deposits in the brain than for the pure choriocarcinomas (6.5 mos. vs. 1 mo.)."}
{"id": "PMID:228845", "title": "Breast cancer in a man 30 years after radiation for metastatic osteogenic sarcoma.", "content": "A man developed breast cancer 30 years after chest radiation for metastatic osteogenic sarcoma. At least eight previous cases of radiation-associated breast cancers have been reported in males, but this man represents the first to develop breast cancer following a childhood malignancy.", "contents": "Breast cancer in a man 30 years after radiation for metastatic osteogenic sarcoma. A man developed breast cancer 30 years after chest radiation for metastatic osteogenic sarcoma. At least eight previous cases of radiation-associated breast cancers have been reported in males, but this man represents the first to develop breast cancer following a childhood malignancy."}
{"id": "PMID:228846", "title": "Carcinogenic chemicals enhance mouse leukemia virus infection in contact-inhibited culture: a new simple method of screening carcinogens.", "content": "Carcinogenic chemicals enhanced infection in contact-inhibited cells with mouse leukemia virus. A correlation was found between the enhancing effects and the carcinogenicities of the 40 chemicals tested. The tumor promoter 12-O-tetradecanoylphorbol-13-acetate did not enhance viral infection.", "contents": "Carcinogenic chemicals enhance mouse leukemia virus infection in contact-inhibited culture: a new simple method of screening carcinogens. Carcinogenic chemicals enhanced infection in contact-inhibited cells with mouse leukemia virus. A correlation was found between the enhancing effects and the carcinogenicities of the 40 chemicals tested. The tumor promoter 12-O-tetradecanoylphorbol-13-acetate did not enhance viral infection."}
{"id": "PMID:228847", "title": "Adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate phosphodiesterase activities in 1,2-dimethylhydrazine induced colon adenocarcinoma.", "content": "The intracellular concentrations of adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) in 1,2-dimethylhydrazine (DMH) induced rat colon tumors were previously reported to be one-half and twice, respectively, that measured in normal rat colon tissue. The results of this present study indicate that the total amount of cyclic nucleotide hydrolysis by the phosphodiesterase enzymes (PDE) could account for the lower cAMP and elevated cGMP noted in cancer tissue. PDE activities in homogenates prepared from normal and neoplastic tissue showed general similarities in both their hydrogen and metal ion dependencies with optimum degradation of nucleotides occurring at pH 7.2-7.8 in the presence of either Mg2+ or Mn2+ ions. The enzymes from both tissue types were inhibited to a similar extent by papaverine and theophylline. Distribution studies indicated PDE activities were similar throughout the entire length of the normal colon; consequently, the anomalous activities measured in the tumors were attributable to the specific cell population and not to the particular site at which malignancy arose. Thus, the findings of this study suggest that one cause for lowered cAMP and elevated cGMP levels in DMH induced colon adenocarcinomas was the amount of cyclic nucleotide hydrolysis by PDE in the malignant tissue.", "contents": "Adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate phosphodiesterase activities in 1,2-dimethylhydrazine induced colon adenocarcinoma. The intracellular concentrations of adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) in 1,2-dimethylhydrazine (DMH) induced rat colon tumors were previously reported to be one-half and twice, respectively, that measured in normal rat colon tissue. The results of this present study indicate that the total amount of cyclic nucleotide hydrolysis by the phosphodiesterase enzymes (PDE) could account for the lower cAMP and elevated cGMP noted in cancer tissue. PDE activities in homogenates prepared from normal and neoplastic tissue showed general similarities in both their hydrogen and metal ion dependencies with optimum degradation of nucleotides occurring at pH 7.2-7.8 in the presence of either Mg2+ or Mn2+ ions. The enzymes from both tissue types were inhibited to a similar extent by papaverine and theophylline. Distribution studies indicated PDE activities were similar throughout the entire length of the normal colon; consequently, the anomalous activities measured in the tumors were attributable to the specific cell population and not to the particular site at which malignancy arose. Thus, the findings of this study suggest that one cause for lowered cAMP and elevated cGMP levels in DMH induced colon adenocarcinomas was the amount of cyclic nucleotide hydrolysis by PDE in the malignant tissue."}
{"id": "PMID:228848", "title": "Glycolytic enzyme activities in malignant cells grown in vitro and in vivo.", "content": "Cell proximity has a profound effect on the glycolytic enzyme levels observed in mammalian cells grown in vitro. Hexokinase activity generally increased with the increasing cell density of both untransformed and virus-transformed cultures. In contrast, phosphofructokinase and pyruvate kinase activities were generally elevated only in crowded cultures of transformed cells. A spontaneous experimental mouse tumor cell line (EMT6) exhibited cell crowding-dependent elevations in glycolytic enzyme levels when cultured in vitro. The glycolytic enzyme levels of experimental mouse tumors grown in vivo, on the other hand, were constant and normally less than those observed in cultured EMT6 cells.", "contents": "Glycolytic enzyme activities in malignant cells grown in vitro and in vivo. Cell proximity has a profound effect on the glycolytic enzyme levels observed in mammalian cells grown in vitro. Hexokinase activity generally increased with the increasing cell density of both untransformed and virus-transformed cultures. In contrast, phosphofructokinase and pyruvate kinase activities were generally elevated only in crowded cultures of transformed cells. A spontaneous experimental mouse tumor cell line (EMT6) exhibited cell crowding-dependent elevations in glycolytic enzyme levels when cultured in vitro. The glycolytic enzyme levels of experimental mouse tumors grown in vivo, on the other hand, were constant and normally less than those observed in cultured EMT6 cells."}
{"id": "PMID:228849", "title": "Inhibitors for the mutagenicities of colon carcinogens, 1,2-dimethylhydrazine and azoxymethane, in the host-mediated assay.", "content": "Inhibitory effects of several chemicals on the mutagenicities of 1,2-dimethylhydrazine (DMH) and azoxymethane (AOM) for Salmonella typhimurium G46 in the host-mediated assay were investigated. They were carbon disulfide (CS2), tetraethylthiuram disulfide (disulfiram, DSF), sodium diethyldithiocarbamate (SDDC), ethylene-bis(dithiocarbamato) manganese (Maneb), pyrazole (PZ), aminoacetonitrile hydrogen sulfate (AAN), and sodium selenite (SE). All the compounds, except for SE, inhibited the mutagenicities of DMH and AOM.", "contents": "Inhibitors for the mutagenicities of colon carcinogens, 1,2-dimethylhydrazine and azoxymethane, in the host-mediated assay. Inhibitory effects of several chemicals on the mutagenicities of 1,2-dimethylhydrazine (DMH) and azoxymethane (AOM) for Salmonella typhimurium G46 in the host-mediated assay were investigated. They were carbon disulfide (CS2), tetraethylthiuram disulfide (disulfiram, DSF), sodium diethyldithiocarbamate (SDDC), ethylene-bis(dithiocarbamato) manganese (Maneb), pyrazole (PZ), aminoacetonitrile hydrogen sulfate (AAN), and sodium selenite (SE). All the compounds, except for SE, inhibited the mutagenicities of DMH and AOM."}
{"id": "PMID:228850", "title": "Mutagenicity of chamuvaritin: a benzyldihydrochalcone isolated from a medicinal plant.", "content": "The mutagenic effects of chamuvaritin, dihydrobenzylchalcone isolated from Uvaria chamae, were investigated using Salmonella typhimurium tester strains TA92, TA94--98, TA100--1535, TA1537 and TA1538. The phytochemical was mutagenic in tester strains TA98 and TA100 and required activation by the hepatic S-9 microsomal enzyme preparation.", "contents": "Mutagenicity of chamuvaritin: a benzyldihydrochalcone isolated from a medicinal plant. The mutagenic effects of chamuvaritin, dihydrobenzylchalcone isolated from Uvaria chamae, were investigated using Salmonella typhimurium tester strains TA92, TA94--98, TA100--1535, TA1537 and TA1538. The phytochemical was mutagenic in tester strains TA98 and TA100 and required activation by the hepatic S-9 microsomal enzyme preparation."}
{"id": "PMID:228855", "title": "Fine structure of the rabbit adrenal cortex and the effects of short-term ACTH administration.", "content": "The fine structure of the rabbit adrenal cortex was investigated. The parenchymal cells display the ultrastructural features of steroid-producing cells, and also contain numerous electron-dense bodies frequently located near intercellular canaliculi, when open into the subendothelial space. Short-term ACTH-administration induced a noticeable decrease in the volume of the lipid compartment in the cells of all three cortical zones and a significant increase in the volume of dense bodies in the cells of zona fasciculata and zona reticularis. The hypothesis that these dense bodies are secretory granules is discussed in the light of biochemical evidence showing that ACTH increases the concentration of both corticosterone and cortisol in the decapsulated-enucleated adrenal homogenate and does not affect the activity of two lysosome-marker enzymes (i.e., acid phosphatase and beta-glucuronidase).", "contents": "Fine structure of the rabbit adrenal cortex and the effects of short-term ACTH administration. The fine structure of the rabbit adrenal cortex was investigated. The parenchymal cells display the ultrastructural features of steroid-producing cells, and also contain numerous electron-dense bodies frequently located near intercellular canaliculi, when open into the subendothelial space. Short-term ACTH-administration induced a noticeable decrease in the volume of the lipid compartment in the cells of all three cortical zones and a significant increase in the volume of dense bodies in the cells of zona fasciculata and zona reticularis. The hypothesis that these dense bodies are secretory granules is discussed in the light of biochemical evidence showing that ACTH increases the concentration of both corticosterone and cortisol in the decapsulated-enucleated adrenal homogenate and does not affect the activity of two lysosome-marker enzymes (i.e., acid phosphatase and beta-glucuronidase)."}
{"id": "PMID:228856", "title": "Nuclear inclusions in the nerve cells of the sphenopalatine ganglion of the dog.", "content": "Large numbers of nuclear inclusions have been found in the nerve cells of the sphenopalatine ganglia of six healthy adult dogs. Their morphological characteristics are similar to those previously described elsewhere. The presence of simple and granular bodies in normal cells seems to support the hypothesis that these nuclear structures might be considered as normal nuclear organelles related to cellular metabolic activity.", "contents": "Nuclear inclusions in the nerve cells of the sphenopalatine ganglion of the dog. Large numbers of nuclear inclusions have been found in the nerve cells of the sphenopalatine ganglia of six healthy adult dogs. Their morphological characteristics are similar to those previously described elsewhere. The presence of simple and granular bodies in normal cells seems to support the hypothesis that these nuclear structures might be considered as normal nuclear organelles related to cellular metabolic activity."}
{"id": "PMID:228858", "title": "Localization of the ASV src gene product to the plasma membrane of transformed cells by electron microscopic immunocytochemistry.", "content": "The cellular location of the src gene product (p60src) of the Schmidt-Ruppin strain of avian sarcoma virus has been determined by electron microscopic immunocytochemistry in Schmidt-Ruppin ASV-transformed NRK cells, and the amount of the protein in different regions of the cell has been quantified. The protein is concentrated on the inner surface of the plasma membrane, particularly under ruffles, and it is highly concentrated on the inner surface of the membrane near junctions connecting adjacent cells. Small amounts of p60src were detected in the cytoplasm and in the perinuclear Golgi region of the cell. No significant localization was detected in control NRK cells or in NRK cells transformed by the Kirsten strain of murine sarcoma virus. The presence of p60src on the inner surface of the plasma membrane indicates that the changes in cell growth, cell shape and cell membrane structure noted in ASV-transformed cells are due to an initial action of p60src at the cell membrane.", "contents": "Localization of the ASV src gene product to the plasma membrane of transformed cells by electron microscopic immunocytochemistry. The cellular location of the src gene product (p60src) of the Schmidt-Ruppin strain of avian sarcoma virus has been determined by electron microscopic immunocytochemistry in Schmidt-Ruppin ASV-transformed NRK cells, and the amount of the protein in different regions of the cell has been quantified. The protein is concentrated on the inner surface of the plasma membrane, particularly under ruffles, and it is highly concentrated on the inner surface of the membrane near junctions connecting adjacent cells. Small amounts of p60src were detected in the cytoplasm and in the perinuclear Golgi region of the cell. No significant localization was detected in control NRK cells or in NRK cells transformed by the Kirsten strain of murine sarcoma virus. The presence of p60src on the inner surface of the plasma membrane indicates that the changes in cell growth, cell shape and cell membrane structure noted in ASV-transformed cells are due to an initial action of p60src at the cell membrane."}
{"id": "PMID:228872", "title": "Evidence for various degrees of motional freedom of the \"boundary\" lipid in cytochrome oxidase.", "content": "The cytochrome oxidase-lipid complex from beef heart mitochondria after various degrees of lipid extraction has been studied by electron spin resonance spectroscopy using spin labelled fatty acids and phospholipids. With cytochrome oxidase at the lowest lipid content (below 0.2 mg/mg of protein) i.e. at the level sometimes referred to as the \"boundary\" lipid, with spin labelled fatty acids an immobilized spectrum is observed. However, when spin labelled phospholipids are used under the same conditions, a mobile component is also observed. A quantitative estimation of the spectral components by computer analysis has been performed. The difference in behaviour of the spin labelled fatty acids and phospholipids suggest that the part of the residual lipid of the complex, which in some conditions is apparently immobilised, may exhibit in other conditons a considerably high degree of mobility.", "contents": "Evidence for various degrees of motional freedom of the \"boundary\" lipid in cytochrome oxidase. The cytochrome oxidase-lipid complex from beef heart mitochondria after various degrees of lipid extraction has been studied by electron spin resonance spectroscopy using spin labelled fatty acids and phospholipids. With cytochrome oxidase at the lowest lipid content (below 0.2 mg/mg of protein) i.e. at the level sometimes referred to as the \"boundary\" lipid, with spin labelled fatty acids an immobilized spectrum is observed. However, when spin labelled phospholipids are used under the same conditions, a mobile component is also observed. A quantitative estimation of the spectral components by computer analysis has been performed. The difference in behaviour of the spin labelled fatty acids and phospholipids suggest that the part of the residual lipid of the complex, which in some conditions is apparently immobilised, may exhibit in other conditons a considerably high degree of mobility."}
{"id": "PMID:228873", "title": "Mechanism of action of collagenase on the blood-brain barrier permeability. Increase of endothelial cell pinocytotic activity as shown with horse-radish peroxidase as a tracer.", "content": "The ultrastructural mechanism of the protease induced blood-brain barrier permeability-increase was studied with horse-radish peroxidase as a tracer. After intravenous injection of collagenase or pronase, a significantly increased number of pinocytotic vesicles was found in brain capillary endothelial cells. alpha-Chymotrypsine did not exert such an action.", "contents": "Mechanism of action of collagenase on the blood-brain barrier permeability. Increase of endothelial cell pinocytotic activity as shown with horse-radish peroxidase as a tracer. The ultrastructural mechanism of the protease induced blood-brain barrier permeability-increase was studied with horse-radish peroxidase as a tracer. After intravenous injection of collagenase or pronase, a significantly increased number of pinocytotic vesicles was found in brain capillary endothelial cells. alpha-Chymotrypsine did not exert such an action."}
{"id": "PMID:228874", "title": "A transient rise in cyclic AMP levels following chemotactic stimulation of neutrophil granulocytes.", "content": "A short transient rise of cyclic AMP is observed within 1 minute after primary stimulation of neutrophils with chemotactic serum peptides containing classical anaphylatoxin (CAT). A second administration of these peptides after two minutes failed to produce a second peak of cAMP. Human serum albumin (HSA) which has chemokinetic but no chemotactic activities did not change cAMP levels. There was no significant change in cGMP levels within 1 minute following stimulation of rabbit neutrophils with chemotactic peptides or HSA.", "contents": "A transient rise in cyclic AMP levels following chemotactic stimulation of neutrophil granulocytes. A short transient rise of cyclic AMP is observed within 1 minute after primary stimulation of neutrophils with chemotactic serum peptides containing classical anaphylatoxin (CAT). A second administration of these peptides after two minutes failed to produce a second peak of cAMP. Human serum albumin (HSA) which has chemokinetic but no chemotactic activities did not change cAMP levels. There was no significant change in cGMP levels within 1 minute following stimulation of rabbit neutrophils with chemotactic peptides or HSA."}
{"id": "PMID:228877", "title": "Creatine kinase measurement in the 1977 CAP Enzymology Survey: anomalies explained.", "content": "In the recently published results of the 1977 College of American Pathologists Enzymology Survey, Some anomalous results were obtained in measuring the creatine kinase (EC 2.7.3.2) activity of the samples. The cause of these anomalies was discovered to be an arginine kinase (EC 2.7.3.3) contaminant in one of the enzyme pools used to make the samples. The contaminant shows cross reactivity with creatine phosphate and is activated by dithioerythritol but not the other commonly used thiol activators.", "contents": "Creatine kinase measurement in the 1977 CAP Enzymology Survey: anomalies explained. In the recently published results of the 1977 College of American Pathologists Enzymology Survey, Some anomalous results were obtained in measuring the creatine kinase (EC 2.7.3.2) activity of the samples. The cause of these anomalies was discovered to be an arginine kinase (EC 2.7.3.3) contaminant in one of the enzyme pools used to make the samples. The contaminant shows cross reactivity with creatine phosphate and is activated by dithioerythritol but not the other commonly used thiol activators."}
{"id": "PMID:228879", "title": "Separation and partial characterization of new apoproteins from human plasma high density lipoproteins.", "content": "In four patients receiving parenteral fluids, human plasma high density lipoproteins were obtained by sequential ultracentrifugation and delipidated. Apoproteins were resolved by gel filtration on Sephadex G-200, DEAE-cellulose chromatography, and polyacrylamide gel electrophoresis. Sephadex-Fraction V was unusually large (11--33% compared to 3--7% in normal subjects) and was found to contain seven new apoprotein components of an apparent molecular weight (by SDS gel electrophoresis) between 8000 and 11 000. Amino acid analysis showed that all these peptides had a high glycine and arginine content and a very low content of threonine and valine. Isoelectric focusing gave isoelectric points ranging from 5.00 to 8.00. In two patients injected with L-[1-17C]-leucine, incorporation of radioactivity into these peptides gave specific activities of the same order of magnitude as apo C-II and apo C-III. IT may be postulated that these peptides increased significantly when proteins are deficient in the diet or have low levels in plasma. The structural and functional significance of these peptides remains to be determined.", "contents": "Separation and partial characterization of new apoproteins from human plasma high density lipoproteins. In four patients receiving parenteral fluids, human plasma high density lipoproteins were obtained by sequential ultracentrifugation and delipidated. Apoproteins were resolved by gel filtration on Sephadex G-200, DEAE-cellulose chromatography, and polyacrylamide gel electrophoresis. Sephadex-Fraction V was unusually large (11--33% compared to 3--7% in normal subjects) and was found to contain seven new apoprotein components of an apparent molecular weight (by SDS gel electrophoresis) between 8000 and 11 000. Amino acid analysis showed that all these peptides had a high glycine and arginine content and a very low content of threonine and valine. Isoelectric focusing gave isoelectric points ranging from 5.00 to 8.00. In two patients injected with L-[1-17C]-leucine, incorporation of radioactivity into these peptides gave specific activities of the same order of magnitude as apo C-II and apo C-III. IT may be postulated that these peptides increased significantly when proteins are deficient in the diet or have low levels in plasma. The structural and functional significance of these peptides remains to be determined."}
{"id": "PMID:228880", "title": "Effects of thyroid hormones on liver binding sites for human growth hormone, as studied in the rat.", "content": "Several weeks after thyroidectomy (T), female rats stopped growing, and their pituitary GH content had decreased to less than 2--3% of the values found for age-matched controls (C). The liver membranes of such animals were explored with human GH (hGH). It was found that in the severely hypothyroid T rat, the number, but not the affinity, of the lactogenic binding sites was markedly reduced. Treatment of these rats for 3 weeks with 1.75 micrograms or T4 or 0.5 micrograms T3/100 g body weight/day restored growth, increased pituitary GH content and restored the number of liver lactogenic binding sites were practically to normal. As regards the lactogenic binding sites, similar results were obtained when the severely hypothyroid rats were treated with a much lower T4 dose (0.2 microgram/100 g/day): this dose was clearly growth promoting, and restored to normal both the low circulating GH levels and the pituitary PRL content of the severely hypothyroid rat. The changes in plasma PRL were not clear. The lactogenic binding sites on liver membranes from rats which were both thyroidectomized and hypophysectomized were decreased in number. Treatment with 0.5 microgram T3/100 g/day for 30 days (but not for 12 days) resulted in an increase in the number of lactogenic binding sites, though it did not affect growth or the undetectable plasma GH levels. The effect on the lactogenic binding sites was less marked than in T rats with an intact pituitary. It would appear that minute amounts of thyroid hormones are needed for maintenance of liver lactogenic binding sites; it is possible that this not only occurs through mechanism(s) which involve the pituitary, but also through others which do not. The possible role of these receptors in growth processes is not yet clearly understood.", "contents": "Effects of thyroid hormones on liver binding sites for human growth hormone, as studied in the rat. Several weeks after thyroidectomy (T), female rats stopped growing, and their pituitary GH content had decreased to less than 2--3% of the values found for age-matched controls (C). The liver membranes of such animals were explored with human GH (hGH). It was found that in the severely hypothyroid T rat, the number, but not the affinity, of the lactogenic binding sites was markedly reduced. Treatment of these rats for 3 weeks with 1.75 micrograms or T4 or 0.5 micrograms T3/100 g body weight/day restored growth, increased pituitary GH content and restored the number of liver lactogenic binding sites were practically to normal. As regards the lactogenic binding sites, similar results were obtained when the severely hypothyroid rats were treated with a much lower T4 dose (0.2 microgram/100 g/day): this dose was clearly growth promoting, and restored to normal both the low circulating GH levels and the pituitary PRL content of the severely hypothyroid rat. The changes in plasma PRL were not clear. The lactogenic binding sites on liver membranes from rats which were both thyroidectomized and hypophysectomized were decreased in number. Treatment with 0.5 microgram T3/100 g/day for 30 days (but not for 12 days) resulted in an increase in the number of lactogenic binding sites, though it did not affect growth or the undetectable plasma GH levels. The effect on the lactogenic binding sites was less marked than in T rats with an intact pituitary. It would appear that minute amounts of thyroid hormones are needed for maintenance of liver lactogenic binding sites; it is possible that this not only occurs through mechanism(s) which involve the pituitary, but also through others which do not. The possible role of these receptors in growth processes is not yet clearly understood."}
{"id": "PMID:228881", "title": "Changes of urinary cyclic AMP excretion and plasma parathyroid hormone levels before and after parathyroidectomy in patients with primary hyperparathyroidism.", "content": "Urinary cyclic AMP excretion and plasma parathyroid hormone(PTH) levels were examined in three patients with primary hyperparathyroidism before and after parathyroidectomy. Plasma PTH and urinary cyclic AMP in the individual patients decreased in parallel following parathyroidectomy. During surgery there was a statistically significant correlation between PTH levels and cyclic AMP excretion in individual patients. These findings support the claim that the rate of urinary cyclic AMP excretion reflects endogenous PTH activity in patients with primary hyperparathyroidism.", "contents": "Changes of urinary cyclic AMP excretion and plasma parathyroid hormone levels before and after parathyroidectomy in patients with primary hyperparathyroidism. Urinary cyclic AMP excretion and plasma parathyroid hormone(PTH) levels were examined in three patients with primary hyperparathyroidism before and after parathyroidectomy. Plasma PTH and urinary cyclic AMP in the individual patients decreased in parallel following parathyroidectomy. During surgery there was a statistically significant correlation between PTH levels and cyclic AMP excretion in individual patients. These findings support the claim that the rate of urinary cyclic AMP excretion reflects endogenous PTH activity in patients with primary hyperparathyroidism."}
{"id": "PMID:228882", "title": "Evaluation of resection of pituitary microadenoma for the treatment of Cushing's disease in patients with radiologically normal sella turcica.", "content": "Six patients with Cushing's disease and a radiologically normal sella turcica have been treated by transsphenoidal hypophysectomy. Microadenomas were found and removed in five. One patient was in complete remission by 2 months and three by 6 months post-operatively. Two of the remaining patients (one with and the other without a surgically demonstrable tumour) were not cured after 8 and 15 months follow-up, respectively. Our data suggest that pituitary tumours are present in the majority of patients with Cushing's disease. The possibilities of incomplete adenomectomy or of a tumour buried within the gland should be considered in patients in whom pituitary surgery does not induce remission. In one patient, subsequently proven to have a pituitary adenoma, the disease remitted pre-operatively with cyproheptadine, suggesting hypothalamic regulation of the tumour and/or direct drug action at the pituitary level.", "contents": "Evaluation of resection of pituitary microadenoma for the treatment of Cushing's disease in patients with radiologically normal sella turcica. Six patients with Cushing's disease and a radiologically normal sella turcica have been treated by transsphenoidal hypophysectomy. Microadenomas were found and removed in five. One patient was in complete remission by 2 months and three by 6 months post-operatively. Two of the remaining patients (one with and the other without a surgically demonstrable tumour) were not cured after 8 and 15 months follow-up, respectively. Our data suggest that pituitary tumours are present in the majority of patients with Cushing's disease. The possibilities of incomplete adenomectomy or of a tumour buried within the gland should be considered in patients in whom pituitary surgery does not induce remission. In one patient, subsequently proven to have a pituitary adenoma, the disease remitted pre-operatively with cyproheptadine, suggesting hypothalamic regulation of the tumour and/or direct drug action at the pituitary level."}
{"id": "PMID:228883", "title": "Studies on guinea-pig macrophage migration inhibitory factor (MIF). I. Glycoprotein nature and net charge.", "content": "Guinea-pig macrophage migration inhibitory factor (MIF), obtained by the stimulation of sensitized lymph node cells with tuberculin PPD, was characterized as a glycoprotein by the following criteria: (a) its activity is destroyed by 0.02 M sodium periodate; (b) when MIF-containing culture fluids are subjected to precipitation by perchloric acid (final concentration 1 M), the inhibitory activity is recovered in the supernatant; and (c) MIF binds to Sepharose-linked concanavalin A and can be eluted with methyl-alpha-D-glucopyranoside. When MIF-containing culture supernatants are fractionated by isoelectrofocussing, migration inhibitory activity is recovered in a fraction with an isoelectric point of 4.4--4.6.", "contents": "Studies on guinea-pig macrophage migration inhibitory factor (MIF). I. Glycoprotein nature and net charge. Guinea-pig macrophage migration inhibitory factor (MIF), obtained by the stimulation of sensitized lymph node cells with tuberculin PPD, was characterized as a glycoprotein by the following criteria: (a) its activity is destroyed by 0.02 M sodium periodate; (b) when MIF-containing culture fluids are subjected to precipitation by perchloric acid (final concentration 1 M), the inhibitory activity is recovered in the supernatant; and (c) MIF binds to Sepharose-linked concanavalin A and can be eluted with methyl-alpha-D-glucopyranoside. When MIF-containing culture supernatants are fractionated by isoelectrofocussing, migration inhibitory activity is recovered in a fraction with an isoelectric point of 4.4--4.6."}
{"id": "PMID:228884", "title": "Glomus tumor treated by prostaglandin inhibition. Report of a case.", "content": "Glomus tumor is a very painful pericytal lesion of the arteriovenous anastomotic complex that controls circulation in a limb. Glomus tumor usually involves a digit. Prostaglandin inhibition may control the glomus tumor pain, but surgical removal is the cure. When the condition is discovered early, or when there is no gross evidence of tumor, thermography and localized anesthetic blocks are invaluable in arriving at the proper diagnosis.", "contents": "Glomus tumor treated by prostaglandin inhibition. Report of a case. Glomus tumor is a very painful pericytal lesion of the arteriovenous anastomotic complex that controls circulation in a limb. Glomus tumor usually involves a digit. Prostaglandin inhibition may control the glomus tumor pain, but surgical removal is the cure. When the condition is discovered early, or when there is no gross evidence of tumor, thermography and localized anesthetic blocks are invaluable in arriving at the proper diagnosis."}
{"id": "PMID:228885", "title": "Ultrastructure of cartilage in heritable disorders of connective tissue.", "content": "Ultrastruct of cartilage were examined in Marfan syndrome, Menkes kinky hair syndrome, achondroplasia, asphyxiating thoracic dysplasia, mild diastrophic dysplasia and mucopolysaccharidoses I and III. Ruthenium red staining revealed decrease of proteoglycans in cases with Marfan syndrome and kinky hair syndrome, and increase in cases with osteochondrodysplasia and mucopolysaccharidosis III. This morphologic tendency coincided with the result obtained by biochemical analysis of glycosaminoglycan contents in cartilage matrix from cases with Marfan syndrome (decreased content) and asphyxiating thoracic dysplasia (increased content). It was postulated that proteoglycan content in cartilage matrix might be related to excessive or reduced skeletal growth in Marfan syndrome or osteochondrodysplasia.", "contents": "Ultrastructure of cartilage in heritable disorders of connective tissue. Ultrastruct of cartilage were examined in Marfan syndrome, Menkes kinky hair syndrome, achondroplasia, asphyxiating thoracic dysplasia, mild diastrophic dysplasia and mucopolysaccharidoses I and III. Ruthenium red staining revealed decrease of proteoglycans in cases with Marfan syndrome and kinky hair syndrome, and increase in cases with osteochondrodysplasia and mucopolysaccharidosis III. This morphologic tendency coincided with the result obtained by biochemical analysis of glycosaminoglycan contents in cartilage matrix from cases with Marfan syndrome (decreased content) and asphyxiating thoracic dysplasia (increased content). It was postulated that proteoglycan content in cartilage matrix might be related to excessive or reduced skeletal growth in Marfan syndrome or osteochondrodysplasia."}
{"id": "PMID:228886", "title": "Mucosal enzymes in human inflammatory bowel disease with reference to neutrophil granulocytes as mediators of tissue injury.", "content": "1. Biopsies of rectal mucosa were obtained for histology and enzyme analysis from 32 patients with inflammatory and functional bowel disorders, and the biopsies were classified morphologically as active colitis, quiescent colitis or normal. 2. Supernatant fractions of biopsy homogenates were assayed for their content of the proteolytic enzymes alpha-chymotrypsin, elastase and cathepsin D, and of protein, unsaturated vitamin B12-binding capacity, lysozyme, myeloperoxidase and N-acetyl-beta-glucosaminidase. 3. Mean unsaturated vitamin B12-binding capacity was significantly raised above normal in the active colitic mucosa, and mean lysozyme activity was raised above normal in both active and quiescent mucosae. 4. In active colitic mucosa there was no rise above normal in mean activities of any of the proteolytic enzymes, though a significant fall below normal occurred in mean N-acetyl-beta-glucosaminidase activity in the active colitic group.", "contents": "Mucosal enzymes in human inflammatory bowel disease with reference to neutrophil granulocytes as mediators of tissue injury. 1. Biopsies of rectal mucosa were obtained for histology and enzyme analysis from 32 patients with inflammatory and functional bowel disorders, and the biopsies were classified morphologically as active colitis, quiescent colitis or normal. 2. Supernatant fractions of biopsy homogenates were assayed for their content of the proteolytic enzymes alpha-chymotrypsin, elastase and cathepsin D, and of protein, unsaturated vitamin B12-binding capacity, lysozyme, myeloperoxidase and N-acetyl-beta-glucosaminidase. 3. Mean unsaturated vitamin B12-binding capacity was significantly raised above normal in the active colitic mucosa, and mean lysozyme activity was raised above normal in both active and quiescent mucosae. 4. In active colitic mucosa there was no rise above normal in mean activities of any of the proteolytic enzymes, though a significant fall below normal occurred in mean N-acetyl-beta-glucosaminidase activity in the active colitic group."}
{"id": "PMID:228908", "title": "Selective ion monitoring in clinical chemistry.", "content": "The principles of selective ion monitoring are described. Choice of instrumentations, derivatives, and internal standards is discussed. The most important factors influencing sensitivity, specificity, and precision are summarized. Applications of selective ion monitoring for quantitative assay of steroids, fat soluble vitamins, triglycerides, prostaglandins, biogenic amines, amino acids, carbohydrates, and several other organic compounds of clinical interest are critically reviewed. It is concluded that isotope dilution selective ion monitoring is one of the most sensitive and accurate techniques presently available for quantitation of a large number of endogenous compounds of clinical interest. In view of the high accuracy, the technique is useful not only for the clinical chemists dealing with determination of specific compounds which are difficult to analyze by other methods, but also for those dealing with quality control of routine analyses of simple organic compounds.", "contents": "Selective ion monitoring in clinical chemistry. The principles of selective ion monitoring are described. Choice of instrumentations, derivatives, and internal standards is discussed. The most important factors influencing sensitivity, specificity, and precision are summarized. Applications of selective ion monitoring for quantitative assay of steroids, fat soluble vitamins, triglycerides, prostaglandins, biogenic amines, amino acids, carbohydrates, and several other organic compounds of clinical interest are critically reviewed. It is concluded that isotope dilution selective ion monitoring is one of the most sensitive and accurate techniques presently available for quantitation of a large number of endogenous compounds of clinical interest. In view of the high accuracy, the technique is useful not only for the clinical chemists dealing with determination of specific compounds which are difficult to analyze by other methods, but also for those dealing with quality control of routine analyses of simple organic compounds."}
{"id": "PMID:228911", "title": "Changes in optic glass-fibers due to X-ray irradiation.", "content": "The purpose of this study was to clarify the relationship between x-ray irradiation and changes in the functional properties of flexible fiberscopes. Scanning electron microscopy, electron spin resonance, and thermoluminescent dosimetry techniques were used to determine the nature of the changes and their possible reversibility. Decreases in light transmission were observed at exposures above 5 roentgens (R), color changes were observed above 25 R, and electron spin resonance absorption changes occurred above 100 R. These changes were proportional to the x-ray doses. The x-ray exposure rates of the segmental and the subsegmental bronchi are about 20 percent that of the patient's thoracic skin surface. The above-mentioned studies showed that, for optimal results, a fiberscope should not be exposed to more than 15 minutes of fluoroscopy by a TV apparatus per week.", "contents": "Changes in optic glass-fibers due to X-ray irradiation. The purpose of this study was to clarify the relationship between x-ray irradiation and changes in the functional properties of flexible fiberscopes. Scanning electron microscopy, electron spin resonance, and thermoluminescent dosimetry techniques were used to determine the nature of the changes and their possible reversibility. Decreases in light transmission were observed at exposures above 5 roentgens (R), color changes were observed above 25 R, and electron spin resonance absorption changes occurred above 100 R. These changes were proportional to the x-ray doses. The x-ray exposure rates of the segmental and the subsegmental bronchi are about 20 percent that of the patient's thoracic skin surface. The above-mentioned studies showed that, for optimal results, a fiberscope should not be exposed to more than 15 minutes of fluoroscopy by a TV apparatus per week."}
{"id": "PMID:228915", "title": "Free radicals in cancer.", "content": "It has been hypothesized that free radicals play a significant role in cancer. A historical review indicates a series of rises and falls in the acceptance of this hypothesis and it remains controversial. The strongest evidence for a critical role of free radicals in cancer is based on electron spin resonance (e.s.r.) data from lyophilized (freeze-dried) tumours. Recent results indicate that such data are artifactual in the sense that the observed signals are not directly related to free radicals existing before lyophilization. These data also indicate, however, that some of the observed changes are reproducible and may be indirectly linked to biophysical or biochemical changes that occur in tumour cells. A possible key to such a link is via antioxidants, especially ascorbic acid. It is now feasible to do experiments to definitively determine: (1) the generality of the effect of lyophilization on e.s.r. spectra of tumours; (2) the molecular nature of the free radicals observed in lyophilized tumours and normal tissues; (3) the effect of redox reactions and substances on the observed e.s.r. spectra; and (4) the occurrence of free radical changes during carcinogenesis.", "contents": "Free radicals in cancer. It has been hypothesized that free radicals play a significant role in cancer. A historical review indicates a series of rises and falls in the acceptance of this hypothesis and it remains controversial. The strongest evidence for a critical role of free radicals in cancer is based on electron spin resonance (e.s.r.) data from lyophilized (freeze-dried) tumours. Recent results indicate that such data are artifactual in the sense that the observed signals are not directly related to free radicals existing before lyophilization. These data also indicate, however, that some of the observed changes are reproducible and may be indirectly linked to biophysical or biochemical changes that occur in tumour cells. A possible key to such a link is via antioxidants, especially ascorbic acid. It is now feasible to do experiments to definitively determine: (1) the generality of the effect of lyophilization on e.s.r. spectra of tumours; (2) the molecular nature of the free radicals observed in lyophilized tumours and normal tissues; (3) the effect of redox reactions and substances on the observed e.s.r. spectra; and (4) the occurrence of free radical changes during carcinogenesis."}
{"id": "PMID:228914", "title": "A disruption of pachytene DNA metabolism in male mice with chromosomally-derived sterility.", "content": "DNA metabolism was analyzed in spermatocytes of mice that were sterile either because of X-autosome or autosome-autosome translocations, or because of trisomy. In the strains analyzed, spermatogenic development is arrested by metaphase I or soon thereafter. In all such strains a disruption of the normal pattern of pachytene DNA metabolism occurred. Prepachytene metabolism appeared normal. Disruption was manifest in both the level of endogenously generated nicks during pachytene and in the distribution of nicks among the different DNA sequence classes. Nicking was more intense in the steriles and tended to be randomized in distribution. Satellite DNA underwent pachytene nick-repair in the steriles but not in fertile controls. The repair capacity of spermatocytes from steriles was equal to that of the fertiles; the higher frequency of nicks in the steriles was due to a persistence of nicking activity.", "contents": "A disruption of pachytene DNA metabolism in male mice with chromosomally-derived sterility. DNA metabolism was analyzed in spermatocytes of mice that were sterile either because of X-autosome or autosome-autosome translocations, or because of trisomy. In the strains analyzed, spermatogenic development is arrested by metaphase I or soon thereafter. In all such strains a disruption of the normal pattern of pachytene DNA metabolism occurred. Prepachytene metabolism appeared normal. Disruption was manifest in both the level of endogenously generated nicks during pachytene and in the distribution of nicks among the different DNA sequence classes. Nicking was more intense in the steriles and tended to be randomized in distribution. Satellite DNA underwent pachytene nick-repair in the steriles but not in fertile controls. The repair capacity of spermatocytes from steriles was equal to that of the fertiles; the higher frequency of nicks in the steriles was due to a persistence of nicking activity."}
{"id": "PMID:228923", "title": "A rationale for opiate withdrawal symptomatology.", "content": "The discovery of opioid peptide transmitters and the delineation of their interactions with the noradrenergic locus ceruleus (LC) has led to our proposing that opiate effects on mood and physiological responses result from the opiate-induced inhibition of the LC. Withdrawal of opiates removes this \"tonic\" inhibition of the LC and could readily result in a piperoxane-like release from inhibition. The hypothesis that noradrenergic hyperactivity underlies the physiologic and affective changes seen in opiate withdrawal and spontaneous panic seen in man can be readily tested in man by evaluating the efficacy of drugs which inhibit the LC and block piperoxane- and LC-elicited increases in specific behaviors for the treatment of opiate withdrawal and naturally occurring panic-anxiety states in man.", "contents": "A rationale for opiate withdrawal symptomatology. The discovery of opioid peptide transmitters and the delineation of their interactions with the noradrenergic locus ceruleus (LC) has led to our proposing that opiate effects on mood and physiological responses result from the opiate-induced inhibition of the LC. Withdrawal of opiates removes this \"tonic\" inhibition of the LC and could readily result in a piperoxane-like release from inhibition. The hypothesis that noradrenergic hyperactivity underlies the physiologic and affective changes seen in opiate withdrawal and spontaneous panic seen in man can be readily tested in man by evaluating the efficacy of drugs which inhibit the LC and block piperoxane- and LC-elicited increases in specific behaviors for the treatment of opiate withdrawal and naturally occurring panic-anxiety states in man."}
{"id": "PMID:228922", "title": "Rapid adaptation to neuronal membrane effects of ethanol and low temperature: some speculations on mechanism.", "content": "There is increasing evidence that ethanol exerts its primary effect at neuronal membranes by influencing specific lipid--protein or lipid--lipid interactions that control the state of organization of a specific membrane component; for example, a specific lipid--protein complex that controls a particular physiological property. This implies that tolerance to ethanol is the result of a change in the composition and/or state of organization of this critical membrane component. This altered state confers ethanol resistance. It may or may not have an effect on function in the absence of ethanol. One basis for these speculations comes from experiments using a sensitive and specific neurophysiological assay -- the rate of decay of posttetanic potentiation (PTP) at an identified synapse in an isolated, perfused Aplysia ganglion. We review evidence that PTP decay rate is strikingly accelerated by ethanol (a membrane-fluidizing agent) and strikingly decelerated below a transition temperature, presumably reflecting a transition in the structure of a membrane component. The ethanol and low-temperature effects are antagonistic. The system develops adaptation (tolerance) to either ethanol or low temperature within hours of its exposure. Tolerance persists for at least 12 hours, the longest interval tested thus far. In the absence of ethanol and at normal temperature the system behaves normally, that is it shows no \"physical dependence\". The system also has the remarkable property that when it becomes tolerant to either of these treatments, it shows tolerance to the other treatment that normally has the opposite effect. Therefore, the adaptation to either treatment cannot be a simple change in membrane composition governing overall membrane fluidity. A hypothesis which could explain the bidirectional cross-tolerance is considered in which adaptation to both treatments involves a shift from a homogeneous to a more heterogeneous composition of the critical membrane component, for example increasing heterogeneity in boundary lipid surrounding a critical membrane protein. It is becoming increasingly clear that ethanol exerts its primary effect by altering cell membrane structure -- by \"fluidizing\" or expanding neuronal and other membranes [1 - 6]. This effect results when ethanol, a somewhat hydrophobic molecule, intercalates between some fatty acid chains of membranes, reducing the degree of order of their alignment and increasing the lateral mobility of some membrane components. Decrease in the order of the fatty acid chains results in a measurable expansion of the membrane; and the change in fluidity is reflected in the change in mobility of appropriate probes that can be dissolved in the membrane [6, 7]. It is presumed that the physiological effects of ethanol are consequences of its fluidization of some critical membrane components; and that tolerance to ethanol is based on some form of resistance to this fluidization...", "contents": "Rapid adaptation to neuronal membrane effects of ethanol and low temperature: some speculations on mechanism. There is increasing evidence that ethanol exerts its primary effect at neuronal membranes by influencing specific lipid--protein or lipid--lipid interactions that control the state of organization of a specific membrane component; for example, a specific lipid--protein complex that controls a particular physiological property. This implies that tolerance to ethanol is the result of a change in the composition and/or state of organization of this critical membrane component. This altered state confers ethanol resistance. It may or may not have an effect on function in the absence of ethanol. One basis for these speculations comes from experiments using a sensitive and specific neurophysiological assay -- the rate of decay of posttetanic potentiation (PTP) at an identified synapse in an isolated, perfused Aplysia ganglion. We review evidence that PTP decay rate is strikingly accelerated by ethanol (a membrane-fluidizing agent) and strikingly decelerated below a transition temperature, presumably reflecting a transition in the structure of a membrane component. The ethanol and low-temperature effects are antagonistic. The system develops adaptation (tolerance) to either ethanol or low temperature within hours of its exposure. Tolerance persists for at least 12 hours, the longest interval tested thus far. In the absence of ethanol and at normal temperature the system behaves normally, that is it shows no \"physical dependence\". The system also has the remarkable property that when it becomes tolerant to either of these treatments, it shows tolerance to the other treatment that normally has the opposite effect. Therefore, the adaptation to either treatment cannot be a simple change in membrane composition governing overall membrane fluidity. A hypothesis which could explain the bidirectional cross-tolerance is considered in which adaptation to both treatments involves a shift from a homogeneous to a more heterogeneous composition of the critical membrane component, for example increasing heterogeneity in boundary lipid surrounding a critical membrane protein. It is becoming increasingly clear that ethanol exerts its primary effect by altering cell membrane structure -- by \"fluidizing\" or expanding neuronal and other membranes [1 - 6]. This effect results when ethanol, a somewhat hydrophobic molecule, intercalates between some fatty acid chains of membranes, reducing the degree of order of their alignment and increasing the lateral mobility of some membrane components. Decrease in the order of the fatty acid chains results in a measurable expansion of the membrane; and the change in fluidity is reflected in the change in mobility of appropriate probes that can be dissolved in the membrane [6, 7]. It is presumed that the physiological effects of ethanol are consequences of its fluidization of some critical membrane components; and that tolerance to ethanol is based on some form of resistance to this fluidization..."}
{"id": "PMID:228925", "title": "Regulation of ornithine decarboxylase activity in rat ovarian cells in vitro.", "content": "Incubation of rat ovarian cell suspension with human choriogonadotropin (hCG) caused a marked enhancement of ornithine decarboxylase (EC 4.1.1.17) activity after a lag period of several hours. Even though ovarian ornithine decarboxylase could be induced in minimum essential medium by the hormone alone, supplementation of the medium with various sera greatly enhanced the stimulation of the enzyme activity. All the sera tested (human, fetal calf and horse) were able to stimulate ornithine decarboxylase activity even in the absence of hCG. Maximum stimulation of the enzyme activity by hCG and/or serum occurred in ovarian cell suspensions prepared from 30 to 33-day-old rats. There was a close correlation between the stimulation of ornithine decarboxylase activity and the accumulation fo cyclic AMP in response to the administration of the hormone (in the presence or absence of serum). However, while various sera alone markedly enhanced ovarian ornithine decarboxylase activity in vitro they, if anything, only marginally stimulated the accumulation of cyclic AMP and the secretion of progesterone in ovarian cells in the absence of gonadotropin. A similar dissociation of the stimulation of ornithine decarboxylase activity from the production of cyclic AMP and progesterone was likewise found when the ovarian cells were incubated in an enriched medium (M199) supplemented with albumin and lactalbumin hydrolysate in the absence of the hormone. Under these culture conditions ornithine decarboxylase activity was strikingly enhanced, greatly exceeding the stimulation obtained with various sera, while the accumulation of cyclic AMP and the secretion of progesterone remained virtually unchanged. Specific inhibition (up to 90%) of gonadotropin-induced ornithine decarboxylase activity by difluoromethyl ornithine or 1,3-diamino-2-propanol had little effect on the ability of the ovarian cells to respond to the hormone with increasing production of cyclic AMP and progesterone. While showing that rat ovarian ornithine decarboxylase can be induced in vitro by choriogonadotropin or various sera, our results indicate that the activation of the enzyme involves at least two different mechanisms: (i) One (in response to gonadotropin) involving a prior stimulation of cyclic AMP production, and (ii) another (in response to serum) that is not associated with increases in the accumulation of the cyclic nucleotide.", "contents": "Regulation of ornithine decarboxylase activity in rat ovarian cells in vitro. Incubation of rat ovarian cell suspension with human choriogonadotropin (hCG) caused a marked enhancement of ornithine decarboxylase (EC 4.1.1.17) activity after a lag period of several hours. Even though ovarian ornithine decarboxylase could be induced in minimum essential medium by the hormone alone, supplementation of the medium with various sera greatly enhanced the stimulation of the enzyme activity. All the sera tested (human, fetal calf and horse) were able to stimulate ornithine decarboxylase activity even in the absence of hCG. Maximum stimulation of the enzyme activity by hCG and/or serum occurred in ovarian cell suspensions prepared from 30 to 33-day-old rats. There was a close correlation between the stimulation of ornithine decarboxylase activity and the accumulation fo cyclic AMP in response to the administration of the hormone (in the presence or absence of serum). However, while various sera alone markedly enhanced ovarian ornithine decarboxylase activity in vitro they, if anything, only marginally stimulated the accumulation of cyclic AMP and the secretion of progesterone in ovarian cells in the absence of gonadotropin. A similar dissociation of the stimulation of ornithine decarboxylase activity from the production of cyclic AMP and progesterone was likewise found when the ovarian cells were incubated in an enriched medium (M199) supplemented with albumin and lactalbumin hydrolysate in the absence of the hormone. Under these culture conditions ornithine decarboxylase activity was strikingly enhanced, greatly exceeding the stimulation obtained with various sera, while the accumulation of cyclic AMP and the secretion of progesterone remained virtually unchanged. Specific inhibition (up to 90%) of gonadotropin-induced ornithine decarboxylase activity by difluoromethyl ornithine or 1,3-diamino-2-propanol had little effect on the ability of the ovarian cells to respond to the hormone with increasing production of cyclic AMP and progesterone. While showing that rat ovarian ornithine decarboxylase can be induced in vitro by choriogonadotropin or various sera, our results indicate that the activation of the enzyme involves at least two different mechanisms: (i) One (in response to gonadotropin) involving a prior stimulation of cyclic AMP production, and (ii) another (in response to serum) that is not associated with increases in the accumulation of the cyclic nucleotide."}
{"id": "PMID:228926", "title": "Plasma immunoreactive calcitonin in lung cancer.", "content": "We have measured plasma calcitonin in 135 untreated eucalemic men with lung cancer and a control/smoker population. Calcitonin levels were determined by radioimmunoassay and validated by immunoextraction. Plasma immunoreactive calcitonin moieties were purified by immunoadsorbent chromatography, treated with mercaptoethanol and urea, and characterized by gel filtration. Artifacts in human calcitonin radioimmunoassays of cancer-patient plasmas were detected by parallel plasma incubations in a salmon calcitonin radioimmunoassay system which does not detect human calcitonin and by immunoprecipitation of tracer at the end of radioimmunoassay incubations. Heating fresh plasmas to 65 degrees C for 1.5 hours reduced radioimmunoassay artifacts without loss of calcitonin moieties. Such characterization of hypercalcitoninemia in each of the histopathological types of lung cancer has raised some important questions about the interpretation of plasma calcitonin radioimmunoassay measurements in lung cancer. Based on inhibition of tracer-antibody binding, plasma calcitonin seemed to be elevated in 18% (14/80) of basal plasma samples obtained from patients with epidermoid or with anaplastic lung cancer. Unequivocal hypercalcitoninemia (heat stable, causing no inhibition of antibody-tracer binding in the salmon calcitonin radioimmunoassays, and immunoextractable with human calcitonin antibodies) was not found in any of the apparently hypercalcitoninemic plasmas from persons with epidermoid or anaplastic lung cancer. By contrast, unequivocal hypercalcitoninemia was found in 27% (15/55) of plasmas from patients with small cell carcinoma or adenocarcinoma. Most of the immunoreactive calcitonin recovered from small cell and adenocarcinoma lung cancer plasmas with unequivocally elevated calcitonin is much larger than calcitonin monomer.", "contents": "Plasma immunoreactive calcitonin in lung cancer. We have measured plasma calcitonin in 135 untreated eucalemic men with lung cancer and a control/smoker population. Calcitonin levels were determined by radioimmunoassay and validated by immunoextraction. Plasma immunoreactive calcitonin moieties were purified by immunoadsorbent chromatography, treated with mercaptoethanol and urea, and characterized by gel filtration. Artifacts in human calcitonin radioimmunoassays of cancer-patient plasmas were detected by parallel plasma incubations in a salmon calcitonin radioimmunoassay system which does not detect human calcitonin and by immunoprecipitation of tracer at the end of radioimmunoassay incubations. Heating fresh plasmas to 65 degrees C for 1.5 hours reduced radioimmunoassay artifacts without loss of calcitonin moieties. Such characterization of hypercalcitoninemia in each of the histopathological types of lung cancer has raised some important questions about the interpretation of plasma calcitonin radioimmunoassay measurements in lung cancer. Based on inhibition of tracer-antibody binding, plasma calcitonin seemed to be elevated in 18% (14/80) of basal plasma samples obtained from patients with epidermoid or with anaplastic lung cancer. Unequivocal hypercalcitoninemia (heat stable, causing no inhibition of antibody-tracer binding in the salmon calcitonin radioimmunoassays, and immunoextractable with human calcitonin antibodies) was not found in any of the apparently hypercalcitoninemic plasmas from persons with epidermoid or anaplastic lung cancer. By contrast, unequivocal hypercalcitoninemia was found in 27% (15/55) of plasmas from patients with small cell carcinoma or adenocarcinoma. Most of the immunoreactive calcitonin recovered from small cell and adenocarcinoma lung cancer plasmas with unequivocally elevated calcitonin is much larger than calcitonin monomer."}
{"id": "PMID:228930", "title": "Rat hyperplastic hepatic nodules and primary hepatomas retaining abnormally high pyruvate kinase L type activity.", "content": "As reported in our previous paper (Sato et al., Cancer Res., 38: 3086-3093, 1978), most of the hyperplastic hepatic nodules and primary hepatomas induced by N-2-fluorenylacetamide (2-FAA), diethylnitrosamine (DENA), and 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) showed that pyruvate kinase liver (L) type decreases and the prototypic M2 type increases concomitantly with dedifferentiation of tissues. However, at least 14 samples among 120, mostly hyperplastic nodules and highly differentiated hepatomas induced by 2-FAA or DENA, retained exceptionally high activities of the L type, while other enzymes of carbohydrate metabolism in these tissues deviated toward a common pattern similar to that in the fetal liver. Individual patterns of 9 enzymes including pyruvate kinase of carbohydrate metabolism in these samples are arranged and discussed as examples of unbalanced enzyme deviation in hepatocarcinogenesis.", "contents": "Rat hyperplastic hepatic nodules and primary hepatomas retaining abnormally high pyruvate kinase L type activity. As reported in our previous paper (Sato et al., Cancer Res., 38: 3086-3093, 1978), most of the hyperplastic hepatic nodules and primary hepatomas induced by N-2-fluorenylacetamide (2-FAA), diethylnitrosamine (DENA), and 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) showed that pyruvate kinase liver (L) type decreases and the prototypic M2 type increases concomitantly with dedifferentiation of tissues. However, at least 14 samples among 120, mostly hyperplastic nodules and highly differentiated hepatomas induced by 2-FAA or DENA, retained exceptionally high activities of the L type, while other enzymes of carbohydrate metabolism in these tissues deviated toward a common pattern similar to that in the fetal liver. Individual patterns of 9 enzymes including pyruvate kinase of carbohydrate metabolism in these samples are arranged and discussed as examples of unbalanced enzyme deviation in hepatocarcinogenesis."}
{"id": "PMID:228931", "title": "Influence of coenzyme on the refolding and reassociation in vitro of glyceraldehyde-3-phosphate dehydrogenase from yeast.", "content": "Kinetic analysis of the reactivation in vitro of glyceraldehyde-3-phosphate dehydrogenase from yeast in the presence of NAD+ suggested that transconformation reactions of inactive monomers and their subsequent association to native tetramers are responsible for the sigmoidal relaxations [R. Rudolph et al. (1977) Eur. J. Biochem. 81, 563-570]. Comparison with the reactivation behaviour in the absence of coenzyme was not feasible at this stage due to the instability of the apoenzyme. In the present study, solvent conditions were established which allowed both apoenzyme and holoenzyme to exhibit high stability. The apoenzyme is stable in phosphate buffer; but if excess NAD+ and phosphate are present (both of which stabilize the enzyme if applied separately), destabilization occurs. Protection of functional groups against oxidation by addition of a reducing agent and by degassing and preventing contact with air, increase the stability. Only partial stabilization can be achieved in the presence of NADH. Comparing the kinetics of reactivation in the presence and absence of coenzymes shows that both oxidized and reduced coenzyme enhance the rate of reactivation significantly, and to the same extent. The kinetic effect of coenzyme binding to the refolding polypeptide chain is discussed in terms of the stabilization of intermediates or end products of reconstitution on the one hand, and acceleration of folding and association reactions, on the other.", "contents": "Influence of coenzyme on the refolding and reassociation in vitro of glyceraldehyde-3-phosphate dehydrogenase from yeast. Kinetic analysis of the reactivation in vitro of glyceraldehyde-3-phosphate dehydrogenase from yeast in the presence of NAD+ suggested that transconformation reactions of inactive monomers and their subsequent association to native tetramers are responsible for the sigmoidal relaxations [R. Rudolph et al. (1977) Eur. J. Biochem. 81, 563-570]. Comparison with the reactivation behaviour in the absence of coenzyme was not feasible at this stage due to the instability of the apoenzyme. In the present study, solvent conditions were established which allowed both apoenzyme and holoenzyme to exhibit high stability. The apoenzyme is stable in phosphate buffer; but if excess NAD+ and phosphate are present (both of which stabilize the enzyme if applied separately), destabilization occurs. Protection of functional groups against oxidation by addition of a reducing agent and by degassing and preventing contact with air, increase the stability. Only partial stabilization can be achieved in the presence of NADH. Comparing the kinetics of reactivation in the presence and absence of coenzymes shows that both oxidized and reduced coenzyme enhance the rate of reactivation significantly, and to the same extent. The kinetic effect of coenzyme binding to the refolding polypeptide chain is discussed in terms of the stabilization of intermediates or end products of reconstitution on the one hand, and acceleration of folding and association reactions, on the other."}
{"id": "PMID:228932", "title": "Crystal and molecular structure of adenosine 5'-O-phosphorothioate O-p-nitrophenyl ester (Sp diastereomer). Substrate stereospecificity of snake venom phosphodiesterase.", "content": "Phosphorylation of 2',3'-O-methoxymethylidene adenosine with bis(p-nitrophenyl) O,O-phosphorochloridothioate, followed by alkaline and acidic deprotection, afforded a mixture of the Rp and Sp diastereomers of adenosine 5'-O-phosphorothioate O-p-nitrophenyl ester in good yield. Only one of these diastereomers is a substrate for snake venom phosphodiesterase. The other diastereomer, remaining after complete enzymatic digestion of the substrate, was crystallized as the triethylammonium salt in the triclinic space group P1. The structure was solved from three-dimensional X-ray data and refined to an R value of 5.2%. The asymmetric cell unit contains two independent molecules with almost identical conformations. The ribose is puckered C(2')-endo, the heterocycle is in anti position and the C(5')-O(5') bond gauche, gauche. The triethylammonium cation is coordinated to the free oxygen of the phosphorothioate group and the P-S bond has double bond character. The absolute configuration of the phosphorous is Sp. This is in agreement with an earlier stereochemical study of the hydrolysis of the diastereomers of 5'-O-adenosyl 3'-O-uridyl phosphorothioate by snake venom phosphodiesterase.", "contents": "Crystal and molecular structure of adenosine 5'-O-phosphorothioate O-p-nitrophenyl ester (Sp diastereomer). Substrate stereospecificity of snake venom phosphodiesterase. Phosphorylation of 2',3'-O-methoxymethylidene adenosine with bis(p-nitrophenyl) O,O-phosphorochloridothioate, followed by alkaline and acidic deprotection, afforded a mixture of the Rp and Sp diastereomers of adenosine 5'-O-phosphorothioate O-p-nitrophenyl ester in good yield. Only one of these diastereomers is a substrate for snake venom phosphodiesterase. The other diastereomer, remaining after complete enzymatic digestion of the substrate, was crystallized as the triethylammonium salt in the triclinic space group P1. The structure was solved from three-dimensional X-ray data and refined to an R value of 5.2%. The asymmetric cell unit contains two independent molecules with almost identical conformations. The ribose is puckered C(2')-endo, the heterocycle is in anti position and the C(5')-O(5') bond gauche, gauche. The triethylammonium cation is coordinated to the free oxygen of the phosphorothioate group and the P-S bond has double bond character. The absolute configuration of the phosphorous is Sp. This is in agreement with an earlier stereochemical study of the hydrolysis of the diastereomers of 5'-O-adenosyl 3'-O-uridyl phosphorothioate by snake venom phosphodiesterase."}
{"id": "PMID:228936", "title": "Purification and primary structure of cytochrome c-552 from the cyanobacterium, Synechococcus PCC 6312.", "content": "Cytochrome c-552 (soluble 'cytochrome f') from the unicellular cyanobacterium Synechococcus PCC 6312 (ATCC 27167) was purified and the primary structure determined. The proposed sequence consists of one polypeptide chain of 87 residues. The sequence was determined by a combination of chemical and enzymatic cleavage, manual and automatic sequencing and mass spectroscopy. This is the first amino acid sequence of this cytochrome from a unicellular cyanobacterium to be determined in a study of the variation in primary structure between phylogenetically distant cyanobacteria. The sequence is compared to the primary structures of the cytochrome from filamentous cyanobacteria and from eukaryotic algae. The significance of these sequence comparisons to the current hypotheses concerning the origin of eukaryotic cells and their chloroplasts is discussed.", "contents": "Purification and primary structure of cytochrome c-552 from the cyanobacterium, Synechococcus PCC 6312. Cytochrome c-552 (soluble 'cytochrome f') from the unicellular cyanobacterium Synechococcus PCC 6312 (ATCC 27167) was purified and the primary structure determined. The proposed sequence consists of one polypeptide chain of 87 residues. The sequence was determined by a combination of chemical and enzymatic cleavage, manual and automatic sequencing and mass spectroscopy. This is the first amino acid sequence of this cytochrome from a unicellular cyanobacterium to be determined in a study of the variation in primary structure between phylogenetically distant cyanobacteria. The sequence is compared to the primary structures of the cytochrome from filamentous cyanobacteria and from eukaryotic algae. The significance of these sequence comparisons to the current hypotheses concerning the origin of eukaryotic cells and their chloroplasts is discussed."}
{"id": "PMID:228937", "title": "Liver phosphorylase b kinase. Cyclic-AMP-mediated activation and properties of the partially purified rat-liver enzyme.", "content": "Phosphorylase b kinase was extensively purified from rat liver. It was located in a form which could be activated 20--30-fold by a preincubation with adenosine 3':5'-monophosphate (cyclic AMP) and ATP-Mg. This activation was time-dependent, and was paralleled by a simultaneous incorporation of 32P from [gamma-32P]ATP into two polypeptides which comigrated in sodium dodecyl sulfate gel electrophoresis with the alpha and beta subunits of rabbit skeletal muscle phosphorylase b kinase. The liver enzyme was eluted from Sepharose 4B and Bio-Gel A-50m columns at the same place as muscle phosphorylase b kinase, which is indicative of a molecular weight of 1.3 x 10(6). After activation, the most purified liver preparation had a specific activity about 10-fold less than the homogeneous muscle enzyme at pH 8.2. The inactive enzyme form had a pronounced pH optimum around pH 6.0, whereas the activated form was mostly active above neutral pH. The activation of the enzyme reduced the Km for its substrate phosphorylase b severalfold. Liver phosphorylase b kinase was shown to be partially dependent on Ca2+ ions for its activity: addition of 0.5 mM [ethylenebis-(oxoethylenenitrilo)]tetraacetic acid (EGTA) to the phosphorylase b kinase assay increased the Km for phosphorylase b about twofold for both the inactive and the activated form of liver phosphorylase b kinase, but affected the V of the inactive species only.", "contents": "Liver phosphorylase b kinase. Cyclic-AMP-mediated activation and properties of the partially purified rat-liver enzyme. Phosphorylase b kinase was extensively purified from rat liver. It was located in a form which could be activated 20--30-fold by a preincubation with adenosine 3':5'-monophosphate (cyclic AMP) and ATP-Mg. This activation was time-dependent, and was paralleled by a simultaneous incorporation of 32P from [gamma-32P]ATP into two polypeptides which comigrated in sodium dodecyl sulfate gel electrophoresis with the alpha and beta subunits of rabbit skeletal muscle phosphorylase b kinase. The liver enzyme was eluted from Sepharose 4B and Bio-Gel A-50m columns at the same place as muscle phosphorylase b kinase, which is indicative of a molecular weight of 1.3 x 10(6). After activation, the most purified liver preparation had a specific activity about 10-fold less than the homogeneous muscle enzyme at pH 8.2. The inactive enzyme form had a pronounced pH optimum around pH 6.0, whereas the activated form was mostly active above neutral pH. The activation of the enzyme reduced the Km for its substrate phosphorylase b severalfold. Liver phosphorylase b kinase was shown to be partially dependent on Ca2+ ions for its activity: addition of 0.5 mM [ethylenebis-(oxoethylenenitrilo)]tetraacetic acid (EGTA) to the phosphorylase b kinase assay increased the Km for phosphorylase b about twofold for both the inactive and the activated form of liver phosphorylase b kinase, but affected the V of the inactive species only."}
{"id": "PMID:228938", "title": "Ascorbate oxidase from Cucurbita pepo medullosa. New method of purification and reinvestigation of properties.", "content": "1. Ascorbate oxidase has been isolated from the green squash Cucurbita pepo medullosa by a new purification method. Furthermore a low-molecular-weight copper protein containing one type-1 copper/20000 Mr could be separated during the purification of the oxidase. The six-step procedure developed improved the yield of ascorbate oxidase by a factor of 2.5. The method is well reproducible and a constant value of 8 Cu (7.95 +/- 0.1/140000 Mr) has been established. By ultracentrifugal and electrophoretic criteria the enzyme preparations have been found to be homogeneous. They exhibited a specific activity of 3930 +/- 50 units/mg protein or 1088 +/- 15 units/microgram copper. 2. The pure enzyme is characterized by the following optical purity indices: A280/A610 = 25 +/- 0.5, A330/A610 = 0.65 +/- 0.05 and A610/A500 = 7.0 +/- 0.25. The molar absorption coeffient of the characteristic absorption maximum at 610 nm (oxidized minus reduced) amounts of 9700 M-1 cm-1 . 3. Computer simulations of the electron paramagnetic resonance (EPR) spectra of the oxidized enzyme reveal the following parameters: for the type-1 (blue) copper gz = 2.227, gy = 2.058, gx = 2.036; Az = 5.0 mT, Ay = Ax = 0.5 mT, for the type-2 (non-blue) copper g parallel to = 2.242, g perpendicular = 2.053; A parallel to = 19.0 mT, A perpendicular 0.5 mT. Out of the eight copper atoms present in the oxidase four are detectable by EPR. Of these, three belong to the type-1 class, and one to the type-2 class, as demonstrated by computer simulations of the EPR spectra. 4. To achieve full reduction of the enzyme, as measured by bleaching of the blue chromophore, four equivalents of L-ascorbate or reductase must be added in the absence of molecular oxygen. Upon reduction of the enzyme the fluorescence at 330 nm (lambda max ex = 295 nm) is enhanced by a factor of 1.5 to 1.75. The reduced enzyme is readily reoxidized by dioxygen, ferricyanide or hydrogen peroxide. It binds two molecules of hydrogen peroxide in the oxidized state (1/type-3 Cu pair), which can be monitored by a characteristic increase of the absorbance around 310 nm (delta epsilon = 1000 +/- 50 M-1 cm-1). Corresponding changes in EPR and fluorescence spectra have not been detected.", "contents": "Ascorbate oxidase from Cucurbita pepo medullosa. New method of purification and reinvestigation of properties. 1. Ascorbate oxidase has been isolated from the green squash Cucurbita pepo medullosa by a new purification method. Furthermore a low-molecular-weight copper protein containing one type-1 copper/20000 Mr could be separated during the purification of the oxidase. The six-step procedure developed improved the yield of ascorbate oxidase by a factor of 2.5. The method is well reproducible and a constant value of 8 Cu (7.95 +/- 0.1/140000 Mr) has been established. By ultracentrifugal and electrophoretic criteria the enzyme preparations have been found to be homogeneous. They exhibited a specific activity of 3930 +/- 50 units/mg protein or 1088 +/- 15 units/microgram copper. 2. The pure enzyme is characterized by the following optical purity indices: A280/A610 = 25 +/- 0.5, A330/A610 = 0.65 +/- 0.05 and A610/A500 = 7.0 +/- 0.25. The molar absorption coeffient of the characteristic absorption maximum at 610 nm (oxidized minus reduced) amounts of 9700 M-1 cm-1 . 3. Computer simulations of the electron paramagnetic resonance (EPR) spectra of the oxidized enzyme reveal the following parameters: for the type-1 (blue) copper gz = 2.227, gy = 2.058, gx = 2.036; Az = 5.0 mT, Ay = Ax = 0.5 mT, for the type-2 (non-blue) copper g parallel to = 2.242, g perpendicular = 2.053; A parallel to = 19.0 mT, A perpendicular 0.5 mT. Out of the eight copper atoms present in the oxidase four are detectable by EPR. Of these, three belong to the type-1 class, and one to the type-2 class, as demonstrated by computer simulations of the EPR spectra. 4. To achieve full reduction of the enzyme, as measured by bleaching of the blue chromophore, four equivalents of L-ascorbate or reductase must be added in the absence of molecular oxygen. Upon reduction of the enzyme the fluorescence at 330 nm (lambda max ex = 295 nm) is enhanced by a factor of 1.5 to 1.75. The reduced enzyme is readily reoxidized by dioxygen, ferricyanide or hydrogen peroxide. It binds two molecules of hydrogen peroxide in the oxidized state (1/type-3 Cu pair), which can be monitored by a characteristic increase of the absorbance around 310 nm (delta epsilon = 1000 +/- 50 M-1 cm-1). Corresponding changes in EPR and fluorescence spectra have not been detected."}
{"id": "PMID:228939", "title": "Mavicyanin, a blue copper protein from Cucurbita pepo medullosa. Purification and characterization.", "content": "1. The copper protein mavicyanin has been isolated and purified from the green squash Cucurbita pepo medullosa. 2. Mavicyanin contains one type-1 copper/18000 Mr, which can be characterized by: intense absorption maximum at 600 nm (epsilon = 5000 M-1 cm-1/Cu, A280/A600 = 8.0 +/- 0.5, A600/A403 = 7.0 +/- 0.25, maximum of fluorescence emission at 335 nM. 3. In the oxidized state the copper of mavicyanin is 100% detectable by electron paramagnetic resonance (EPR). Computer simulation of the rhombic EPR signal gives gz = 2.287, gy = 2.077, gx = 2.025, Az = 3.5 mT, Ay = 2.9 mT and Ax = 5.7 mT. 4. Like other simple type-1 copper proteins, such as stellacyanin, azurin or plastocyanin, mavicyanin is readily reduced by hydroquinone or L-ascorbic acid. Its midpoint potential E'm was determined to be + 285 mV. The reduced protein reacts rather slowly with dioxygen, but is rapidly reoxidized by ferricyanide.", "contents": "Mavicyanin, a blue copper protein from Cucurbita pepo medullosa. Purification and characterization. 1. The copper protein mavicyanin has been isolated and purified from the green squash Cucurbita pepo medullosa. 2. Mavicyanin contains one type-1 copper/18000 Mr, which can be characterized by: intense absorption maximum at 600 nm (epsilon = 5000 M-1 cm-1/Cu, A280/A600 = 8.0 +/- 0.5, A600/A403 = 7.0 +/- 0.25, maximum of fluorescence emission at 335 nM. 3. In the oxidized state the copper of mavicyanin is 100% detectable by electron paramagnetic resonance (EPR). Computer simulation of the rhombic EPR signal gives gz = 2.287, gy = 2.077, gx = 2.025, Az = 3.5 mT, Ay = 2.9 mT and Ax = 5.7 mT. 4. Like other simple type-1 copper proteins, such as stellacyanin, azurin or plastocyanin, mavicyanin is readily reduced by hydroquinone or L-ascorbic acid. Its midpoint potential E'm was determined to be + 285 mV. The reduced protein reacts rather slowly with dioxygen, but is rapidly reoxidized by ferricyanide."}
{"id": "PMID:228945", "title": "A possibe alpha-adrenergic mechanism for drug (CRL 40028)-induced hyperactivity.", "content": "CRL 40028 (benzhydryl sulfinyl acetohydroxamic acid)-induced stimulation in mice, measured as an increase in locomotor activity was studied following an intraperitoneal injection of drugs known to block alpha-adrenergic receptors. Phenoxybenzamine (20 mg/kg), prazosin (0.5-1 mg/kg) and yohimbine (2 mg/kg) prevented the development of CRL 40028-induced hyperactivity. These results suggest that stimulation of an alpha-adrenergic postsynaptic receptor is of importance for the stimulant effect of CRL 40028.", "contents": "A possibe alpha-adrenergic mechanism for drug (CRL 40028)-induced hyperactivity. CRL 40028 (benzhydryl sulfinyl acetohydroxamic acid)-induced stimulation in mice, measured as an increase in locomotor activity was studied following an intraperitoneal injection of drugs known to block alpha-adrenergic receptors. Phenoxybenzamine (20 mg/kg), prazosin (0.5-1 mg/kg) and yohimbine (2 mg/kg) prevented the development of CRL 40028-induced hyperactivity. These results suggest that stimulation of an alpha-adrenergic postsynaptic receptor is of importance for the stimulant effect of CRL 40028."}
{"id": "PMID:228946", "title": "Separation of human brain angiotensin-converting enzyme from enkephalin-degrading activity.", "content": "Angiotensin-converting enzyme and enkephalin-degrading enzyme activities were solubilized and purified from a particulate fraction of human diencephalon. Converting enzyme activity and enkephalin-degrading activity elute in different fractions following ion exchange chromatography on DEAE-cellulose, suggesting that they are different enzymes. Both enzymes were purified further by ion exchange chromatography on hydroxylapatite and by gel filtration on Sephadex G-200. The purified enzymes had markedly different sensitivities to known inhibitors of angiotensin-converting enzyme. The data do not support the hypothesis that angiotensin-converting enzyme and enkephalin degrading-enzyme are identical.", "contents": "Separation of human brain angiotensin-converting enzyme from enkephalin-degrading activity. Angiotensin-converting enzyme and enkephalin-degrading enzyme activities were solubilized and purified from a particulate fraction of human diencephalon. Converting enzyme activity and enkephalin-degrading activity elute in different fractions following ion exchange chromatography on DEAE-cellulose, suggesting that they are different enzymes. Both enzymes were purified further by ion exchange chromatography on hydroxylapatite and by gel filtration on Sephadex G-200. The purified enzymes had markedly different sensitivities to known inhibitors of angiotensin-converting enzyme. The data do not support the hypothesis that angiotensin-converting enzyme and enkephalin degrading-enzyme are identical."}
{"id": "PMID:228948", "title": "Cyclic AMP in the rat cerebral cortex after stimulation of the locus coeruleus: decrease by antidepressant drugs.", "content": "The study concerned the effect of repeated treatment with antidepressant drugs on the elevation of cyclic AMP levels in the rat cerebral cortex following electrical stimulation of the locus coeruleus. Some of the tricyclic and tetracyclic antidepressant drugs inhibited the cyclic AMP response. Desmethylimipramine was the most potent (effective when given 5 mg/kg/day for 2 weeks). Imipramine and nomifensine (daily dose 10 mg/kg for 2 weeks) produced slight decreases, while iprindol and clomipramine were ineffective. After 6 weeks of treatment (daily 10 mg/kg) iprindol, clomipramine and mianserin were without effect. The cyclic AMP response was suppressed by higher doses of the latter two drugs (2 weeks, 20 mg/kg/day). These results indicate that tricyclic and tetracyclic antidepressant drugs are able to decrease cerebral noradrenergic neurotransmission of locus coeruleus neurons, as far as this is mediated by cyclic AMP. It is not clear, however, whether such modification is related to the therapeutic action of antidepressant drugs.", "contents": "Cyclic AMP in the rat cerebral cortex after stimulation of the locus coeruleus: decrease by antidepressant drugs. The study concerned the effect of repeated treatment with antidepressant drugs on the elevation of cyclic AMP levels in the rat cerebral cortex following electrical stimulation of the locus coeruleus. Some of the tricyclic and tetracyclic antidepressant drugs inhibited the cyclic AMP response. Desmethylimipramine was the most potent (effective when given 5 mg/kg/day for 2 weeks). Imipramine and nomifensine (daily dose 10 mg/kg for 2 weeks) produced slight decreases, while iprindol and clomipramine were ineffective. After 6 weeks of treatment (daily 10 mg/kg) iprindol, clomipramine and mianserin were without effect. The cyclic AMP response was suppressed by higher doses of the latter two drugs (2 weeks, 20 mg/kg/day). These results indicate that tricyclic and tetracyclic antidepressant drugs are able to decrease cerebral noradrenergic neurotransmission of locus coeruleus neurons, as far as this is mediated by cyclic AMP. It is not clear, however, whether such modification is related to the therapeutic action of antidepressant drugs."}
{"id": "PMID:228963", "title": "Pathogenicity of Mengo virus to mice. III. Potentiation of infection by immunosuppressants.", "content": "Mengo virus has been described to cause, in dependence on the virus dose, lethal panencephalomyelitis and exocrine pancreatitis in mice after i.p. inoculation. Two immunosuppressive agents, cyclophosphamide and 1,3-bis(piperidinomethyl)-5-ethyl-5-phenyl-barbituric acid (ZIMET 176/68), were shown to potentiate Mengo virus infection as demonstrated by histopathology and enhanced mortality. Organotropism of Mengo virus did not change under the drug treatment. However, the histological lesions in brain, spinal cord and pancreas failed to exhibit any inflammatory reaction in case of cyclophosphamide, due to its antiphlogistic properties. Considering the mode of action of the drugs employed and the pathogenesis of Mengo virus infection in mice, it is concluded that in the system used both cyclophosphamide and ZIMET 176/68 exert their potentiating effects by interfering with primary virus-macrophage interaction.", "contents": "Pathogenicity of Mengo virus to mice. III. Potentiation of infection by immunosuppressants. Mengo virus has been described to cause, in dependence on the virus dose, lethal panencephalomyelitis and exocrine pancreatitis in mice after i.p. inoculation. Two immunosuppressive agents, cyclophosphamide and 1,3-bis(piperidinomethyl)-5-ethyl-5-phenyl-barbituric acid (ZIMET 176/68), were shown to potentiate Mengo virus infection as demonstrated by histopathology and enhanced mortality. Organotropism of Mengo virus did not change under the drug treatment. However, the histological lesions in brain, spinal cord and pancreas failed to exhibit any inflammatory reaction in case of cyclophosphamide, due to its antiphlogistic properties. Considering the mode of action of the drugs employed and the pathogenesis of Mengo virus infection in mice, it is concluded that in the system used both cyclophosphamide and ZIMET 176/68 exert their potentiating effects by interfering with primary virus-macrophage interaction."}
{"id": "PMID:228964", "title": "Level of marker enzymes in spermatogenesis on administration of PGF2 alpha in rats.", "content": "Intraperitoneal administration of PGF 2 alpha in rats significantly increased testicular acid phosphatase (p less than 0.05), decreased hyaluronidase (p less than 0.05), whereas the activities of 5'-nucleotidase, N-acetyl-B-glucosaminidase, B-galactosidase and uridine diphosphatase remained unaffected.", "contents": "Level of marker enzymes in spermatogenesis on administration of PGF2 alpha in rats. Intraperitoneal administration of PGF 2 alpha in rats significantly increased testicular acid phosphatase (p less than 0.05), decreased hyaluronidase (p less than 0.05), whereas the activities of 5'-nucleotidase, N-acetyl-B-glucosaminidase, B-galactosidase and uridine diphosphatase remained unaffected."}
{"id": "PMID:228965", "title": "Effects of several preoperative medications on fat cell lipolysis, and activity of adipose tissue cyclic AMP phosphodiesterase.", "content": "Effects were examined of atropine, diazepam, pethidene, promethazine, scopolamine, omnopon and papaverine on basal and noradrenaline-stimulated lipolysis in rat isolated fat cells and on rat adipose tissue cyclic AMP phosphodiesterase activity. Papaverine at high concentration (1 mM) inhibited both basal and hormone-stimulated lipolysis, whereas diazepam enhanced basal lipolysis. At a 'clinical dose', omnopon increased both basal and noradrenaline-stimulated lipolysis. Adipose tissue cAMP phosphodiesterase activity was strongly inhibited by 1 mM diazepam, papaverine, promethazine and omnopon (280 microgram ml-1). Lack of enhancement of lipolysis by the established cAMP phosphodiesterase antagonist papaverine, is compatible with simultaneous inhibition also of adipose adenyl cyclase. Diazepam-stimulated lipolysis is compatible with its phosphodiesterase inhibitory activity. It is proposed that papaverine-containing omnopon may offer some survival advantages during surgical stress by facilitating a caloric supply.", "contents": "Effects of several preoperative medications on fat cell lipolysis, and activity of adipose tissue cyclic AMP phosphodiesterase. Effects were examined of atropine, diazepam, pethidene, promethazine, scopolamine, omnopon and papaverine on basal and noradrenaline-stimulated lipolysis in rat isolated fat cells and on rat adipose tissue cyclic AMP phosphodiesterase activity. Papaverine at high concentration (1 mM) inhibited both basal and hormone-stimulated lipolysis, whereas diazepam enhanced basal lipolysis. At a 'clinical dose', omnopon increased both basal and noradrenaline-stimulated lipolysis. Adipose tissue cAMP phosphodiesterase activity was strongly inhibited by 1 mM diazepam, papaverine, promethazine and omnopon (280 microgram ml-1). Lack of enhancement of lipolysis by the established cAMP phosphodiesterase antagonist papaverine, is compatible with simultaneous inhibition also of adipose adenyl cyclase. Diazepam-stimulated lipolysis is compatible with its phosphodiesterase inhibitory activity. It is proposed that papaverine-containing omnopon may offer some survival advantages during surgical stress by facilitating a caloric supply."}
{"id": "PMID:228966", "title": "Specific inhibition of a calcium dependent activation of brain cyclic AMP phosphodiesterase activity by vinblastine.", "content": "Vinblastine selectively inhibits the activation of brain cyclic AMP phosphodiesterase activity by Ca++-protein activator (50% inhibition by 2 x 10(-5) M). This inhibitory effect was reversed by excessive amounts of the activator, whereas large quantities of Ca++ caused only a slight suppression of the vinblastine effect. This result of vinblastine suggests a new site of its action and also suggests the possible role of protein activator, phosphodiesterase proteins or cyclic nucleotides in the previously known effects of vinblastine in vivo and in vitro.", "contents": "Specific inhibition of a calcium dependent activation of brain cyclic AMP phosphodiesterase activity by vinblastine. Vinblastine selectively inhibits the activation of brain cyclic AMP phosphodiesterase activity by Ca++-protein activator (50% inhibition by 2 x 10(-5) M). This inhibitory effect was reversed by excessive amounts of the activator, whereas large quantities of Ca++ caused only a slight suppression of the vinblastine effect. This result of vinblastine suggests a new site of its action and also suggests the possible role of protein activator, phosphodiesterase proteins or cyclic nucleotides in the previously known effects of vinblastine in vivo and in vitro."}
{"id": "PMID:228967", "title": "Alteration of early T lymphocyte count in patients with herpes genitalis.", "content": "Peripheral blood samples from 52 women, including 16 with herpes genitalis and 36 healthy persons, were studied to enumerate subpopulations of lymphocytes. It was found that the mean percentage of 'active' T lymphocytes was significantly less in the patients with herpes genitalis than in the controls.", "contents": "Alteration of early T lymphocyte count in patients with herpes genitalis. Peripheral blood samples from 52 women, including 16 with herpes genitalis and 36 healthy persons, were studied to enumerate subpopulations of lymphocytes. It was found that the mean percentage of 'active' T lymphocytes was significantly less in the patients with herpes genitalis than in the controls."}
{"id": "PMID:228968", "title": "Corticosteroidogenesis by isolated human adrenal cells: effect of serotonin and serotonin antagonists.", "content": "The direct effect of serotonin and antiserotonin agents on adrenal steroid biosynthesis was studied in isolated adrenal cells derived from patients with Cushing's syndrome. The results indicate that serotonin increases corticosterone production, while the serotonin antagonists cyproheptadine and methysergide depress adrenal steroid - particularly cortisol and aldosterone - biosynthesis.", "contents": "Corticosteroidogenesis by isolated human adrenal cells: effect of serotonin and serotonin antagonists. The direct effect of serotonin and antiserotonin agents on adrenal steroid biosynthesis was studied in isolated adrenal cells derived from patients with Cushing's syndrome. The results indicate that serotonin increases corticosterone production, while the serotonin antagonists cyproheptadine and methysergide depress adrenal steroid - particularly cortisol and aldosterone - biosynthesis."}
{"id": "PMID:228969", "title": "Tangential flow filtration of Bordetella pertussis submerse cultures.", "content": "A procedure is reported for the large scale separation of Bordetella pertussis microorganisms from liquid culture media by tangential flow filtration (cross flow filtration) using anisotropic membranes with a cut-off limit of 1 x 10(6) daltons, and microporous membranes with a pore size of 0.22 micrometer.", "contents": "Tangential flow filtration of Bordetella pertussis submerse cultures. A procedure is reported for the large scale separation of Bordetella pertussis microorganisms from liquid culture media by tangential flow filtration (cross flow filtration) using anisotropic membranes with a cut-off limit of 1 x 10(6) daltons, and microporous membranes with a pore size of 0.22 micrometer."}
{"id": "PMID:228984", "title": "Retrovirus expression in normal and pathogenic processes of man.", "content": "C-type viruses have been isolated from primates only on rare occasions. To date, an endogenous C-type virus of man has not been isolated. Nevertheless, the evidence for C-type viral expression in human tissue increases. Evidence for viral antigen expression during human gestation and the pathogenesis of systemic lupus erythematosus (SLE) is summarized. The data are discussed in connection with the current hypotheses that retroviruses may participate in both normal and abnormal biologic processes.", "contents": "Retrovirus expression in normal and pathogenic processes of man. C-type viruses have been isolated from primates only on rare occasions. To date, an endogenous C-type virus of man has not been isolated. Nevertheless, the evidence for C-type viral expression in human tissue increases. Evidence for viral antigen expression during human gestation and the pathogenesis of systemic lupus erythematosus (SLE) is summarized. The data are discussed in connection with the current hypotheses that retroviruses may participate in both normal and abnormal biologic processes."}
{"id": "PMID:228996", "title": "[Role of the fusimotor system in regulating shivering].", "content": "Spontaneously active gamma-motoneurons were found in muscles of the cat during shivering. The activity of these gamma-motoneurons could be increased by stimulation of thermoreceptors of the subcutaneous vessels and nociceptors. Administration of oxotremorine, nicotin, phentolamine, isoprenaline, and seduxene into the 3rd brain ventricle suppressed the shivering but did not change the firing rate of the gamma-motoneurons. The fusomotor system seems to participate in the segmentary activation of shivering, but not in its supraspinal control.", "contents": "[Role of the fusimotor system in regulating shivering]. Spontaneously active gamma-motoneurons were found in muscles of the cat during shivering. The activity of these gamma-motoneurons could be increased by stimulation of thermoreceptors of the subcutaneous vessels and nociceptors. Administration of oxotremorine, nicotin, phentolamine, isoprenaline, and seduxene into the 3rd brain ventricle suppressed the shivering but did not change the firing rate of the gamma-motoneurons. The fusomotor system seems to participate in the segmentary activation of shivering, but not in its supraspinal control."}
{"id": "PMID:228997", "title": "[Studies on the radioreceptor assay of TSH: the binding of 125I-TSH to the human thyroid receptor and the interaction of LATS-IgG (author's transl)].", "content": "The radioreceptor assay system for TSH is considered to be useful in quantitating the hormone and analyzing the mechanism of its action. The assay was established, and the interaction of abnormal thyroid stimulators in Graves' patients was evaluated in this assay system. A 10,000xg fraction of human thyroid homogenates was used as the receptor. Human TSH supplied from NIH was iodinated by using lactoperoxidase. The binding of 125I-TSH to the receptor was small, and 125I-TSH was further purified by the receptor binding. The receptor (25mg equivalent), purified 125I-TSH, and standard TSH or a sample were incubated at 37 degrees C for 60 min in a final volume of 300 microliters. The binding of 125I-TSH to the receptor was time- and temperature-dependent with optimal binding under the conditions described above. The binding was completely inhibited by the addition of human, bovine and ovine TSH and partially inhibited by high concentrations of HCG, FSH-LH. However, there was no cross reactivity with insulin, prostaglandin E1, E2, T3, T4 and Nal. The assay was sensitive enough to detect 5 to 50 microU of TSH. The amount of TSH bound to the receptor was almost parallel to the TSH concentration which is necessary to stimulate human thyroid adenylate cyclase activity. Studies of dissociation kinetics and Scatchard plot indicated that there were two classes of TSH receptors in the human thyroid. A higher association constant was calculated as 1.5 x 10(8)M-1. LATS-IgG from a patient with Graves' disease completely inhibited the binding of 125I-TSH to the receptor, and studies of Lineweaver-Burk, plot suggested that TSH and LATS-IgG shared common binding sites. The radioreceptor assay of TSH appears to be useful in evaluating the abnormal thyroid stimulators present in Graves' disease.", "contents": "[Studies on the radioreceptor assay of TSH: the binding of 125I-TSH to the human thyroid receptor and the interaction of LATS-IgG (author's transl)]. The radioreceptor assay system for TSH is considered to be useful in quantitating the hormone and analyzing the mechanism of its action. The assay was established, and the interaction of abnormal thyroid stimulators in Graves' patients was evaluated in this assay system. A 10,000xg fraction of human thyroid homogenates was used as the receptor. Human TSH supplied from NIH was iodinated by using lactoperoxidase. The binding of 125I-TSH to the receptor was small, and 125I-TSH was further purified by the receptor binding. The receptor (25mg equivalent), purified 125I-TSH, and standard TSH or a sample were incubated at 37 degrees C for 60 min in a final volume of 300 microliters. The binding of 125I-TSH to the receptor was time- and temperature-dependent with optimal binding under the conditions described above. The binding was completely inhibited by the addition of human, bovine and ovine TSH and partially inhibited by high concentrations of HCG, FSH-LH. However, there was no cross reactivity with insulin, prostaglandin E1, E2, T3, T4 and Nal. The assay was sensitive enough to detect 5 to 50 microU of TSH. The amount of TSH bound to the receptor was almost parallel to the TSH concentration which is necessary to stimulate human thyroid adenylate cyclase activity. Studies of dissociation kinetics and Scatchard plot indicated that there were two classes of TSH receptors in the human thyroid. A higher association constant was calculated as 1.5 x 10(8)M-1. LATS-IgG from a patient with Graves' disease completely inhibited the binding of 125I-TSH to the receptor, and studies of Lineweaver-Burk, plot suggested that TSH and LATS-IgG shared common binding sites. The radioreceptor assay of TSH appears to be useful in evaluating the abnormal thyroid stimulators present in Graves' disease."}
{"id": "PMID:228998", "title": "[Studies on the radioreceptor assay of TSH: the properties of TSH-binding inhibitor immunoglobulins (TBII) in patients with Graves' disease (author's transl)].", "content": "In the radioreceptor assay system for TSH, serum immunoglobulin G (IgG) from some patients with Graves' disease has been shown to inhibit the binding of labelled TSH to its receptor sites. In order to clarify the properties of these TSH-binding inhibitor immunoglobulins (TBII) in patients with Graves' disease, TBII were measured in sera from 31 untreated and 51 131I-treated patients, and their relation to clinical and laboratory findings was studied. TBII were detected in 18 (60%) out of 31 patients with untreated Graves' disease. TBII levels in these patients correlated well with thyroidal 99mTc uptake at 30 min and also with the grade of epithelial hyperplasia of thyroid follicles. There was no significant correlation between TBII and serum T3, serum T4, free T4 index, antibody titers against thyroglobulin and microsomes, or association of exophthalmos. There were many patients with Graves' disease whose sera contained high TBII levels but no detectable bioassayable thyroid-stimulating activity (LATS), and in these patients a close correlation was observed between serum levels of TBII and bioassayable LATS-protector activity. In patients with Graves' disease who had been treated by 131I from 5 to 17 years before, the incidence of TBII was very low at 20% (10/51). All except two cases having TBII were found to be still thyrotoxic. Thus, TBII were detected in 8 out of 10 thyrotoxic patients and in only 2 out of 18 euthyroid and none of 23 hypothyroid patients. These findings suggest that TBII in patients with Graves' disease were in close association with human thyroid stimulating activity, and that TBII might be useful as an indicator for checking the effectiveness of the treatment.", "contents": "[Studies on the radioreceptor assay of TSH: the properties of TSH-binding inhibitor immunoglobulins (TBII) in patients with Graves' disease (author's transl)]. In the radioreceptor assay system for TSH, serum immunoglobulin G (IgG) from some patients with Graves' disease has been shown to inhibit the binding of labelled TSH to its receptor sites. In order to clarify the properties of these TSH-binding inhibitor immunoglobulins (TBII) in patients with Graves' disease, TBII were measured in sera from 31 untreated and 51 131I-treated patients, and their relation to clinical and laboratory findings was studied. TBII were detected in 18 (60%) out of 31 patients with untreated Graves' disease. TBII levels in these patients correlated well with thyroidal 99mTc uptake at 30 min and also with the grade of epithelial hyperplasia of thyroid follicles. There was no significant correlation between TBII and serum T3, serum T4, free T4 index, antibody titers against thyroglobulin and microsomes, or association of exophthalmos. There were many patients with Graves' disease whose sera contained high TBII levels but no detectable bioassayable thyroid-stimulating activity (LATS), and in these patients a close correlation was observed between serum levels of TBII and bioassayable LATS-protector activity. In patients with Graves' disease who had been treated by 131I from 5 to 17 years before, the incidence of TBII was very low at 20% (10/51). All except two cases having TBII were found to be still thyrotoxic. Thus, TBII were detected in 8 out of 10 thyrotoxic patients and in only 2 out of 18 euthyroid and none of 23 hypothyroid patients. These findings suggest that TBII in patients with Graves' disease were in close association with human thyroid stimulating activity, and that TBII might be useful as an indicator for checking the effectiveness of the treatment."}
{"id": "PMID:228999", "title": "[Studies on the radioreceptor assay of TSH: the properties of TSH-binding inhibitor immunoglobulins (TBII) in patients with Hashimoto's thyroiditis (author's transl)].", "content": "TSH-binding inhibitor immunoglobulins (TBII) have been detected not only in patients with Graves' disease but also in those with Hashimoto's thyroiditis by using the radioreceptor assay of TSH. In the present study, the properties of TBII in patients with Hashimoto's thyroiditis are discussed. Two (7%) of 29 patients with Hashimoto's thyroiditis had detectable levels of TBII in their gamma-globulin fractions. Both patients were untreated and clinically hypothyroid. One of them had no goiter, and her thyroidal 99mTc uptake was 0% (normal range: 0.4 approximately 3.0%). Despite having potent TSH-binding inhibitor activity in the TSH radioreceptor assay, her serum or its IgG fraction (H-IgG) did not contain any significant anti-TSH antibody, LATS, LATS-protector or human thyroid adenylate cyclase (AC) stimulating activity. This H-IgG inhibited both human thyroid AC stimulation and c-AMP increase in mice thyroid glands induced by TSH or LATS. Furthermore, her serum caused significant inhibition of 131I-release by LATS in a McKenzie mouse bioassay. The present study demonstrates that the serum of one patient with Hashimoto's thyroiditis contained antibodies which 1) blocked the binding of lablled TSH to the receptor, 2) had no thyroid-stimulating activity by themselves, and 3) inhibited AC stimulation by TSH. Such antibodies may cause unresponsiveness to TSH stimulation, hypothyroidism, and, if this state persists for a long time, eventually may result in atrophy of the thyroid tissue. Further, these data indicate that TBII detected by the TSH radioreceptor assay did not always show thyroid stimulating activities.", "contents": "[Studies on the radioreceptor assay of TSH: the properties of TSH-binding inhibitor immunoglobulins (TBII) in patients with Hashimoto's thyroiditis (author's transl)]. TSH-binding inhibitor immunoglobulins (TBII) have been detected not only in patients with Graves' disease but also in those with Hashimoto's thyroiditis by using the radioreceptor assay of TSH. In the present study, the properties of TBII in patients with Hashimoto's thyroiditis are discussed. Two (7%) of 29 patients with Hashimoto's thyroiditis had detectable levels of TBII in their gamma-globulin fractions. Both patients were untreated and clinically hypothyroid. One of them had no goiter, and her thyroidal 99mTc uptake was 0% (normal range: 0.4 approximately 3.0%). Despite having potent TSH-binding inhibitor activity in the TSH radioreceptor assay, her serum or its IgG fraction (H-IgG) did not contain any significant anti-TSH antibody, LATS, LATS-protector or human thyroid adenylate cyclase (AC) stimulating activity. This H-IgG inhibited both human thyroid AC stimulation and c-AMP increase in mice thyroid glands induced by TSH or LATS. Furthermore, her serum caused significant inhibition of 131I-release by LATS in a McKenzie mouse bioassay. The present study demonstrates that the serum of one patient with Hashimoto's thyroiditis contained antibodies which 1) blocked the binding of lablled TSH to the receptor, 2) had no thyroid-stimulating activity by themselves, and 3) inhibited AC stimulation by TSH. Such antibodies may cause unresponsiveness to TSH stimulation, hypothyroidism, and, if this state persists for a long time, eventually may result in atrophy of the thyroid tissue. Further, these data indicate that TBII detected by the TSH radioreceptor assay did not always show thyroid stimulating activities."}
{"id": "PMID:229000", "title": "[A comparison of various indicators of murine thyroid stimulation by LATS (author's transl)].", "content": "To obtain an in vitro method of LATS assay which is equally sensitive to a McKenzie bioassay, we compared the quality of cAMP generation-stimulation, thyroidal adenyl cyclase stimulation, and the stimulation of T3-release from mouse thyroid slices. Among those indicators of thyroid stimulation, stimulation by IgG of the release of T3 from incubated thyroid slices is the most sensitive, reproducible and reliable indicator, reflecting faithfully the results of a McKenzie bioassay. Stimulation of cAMP generation in slice manifested less sensitivity, but reasonable reproducibility. However, adenyl cyclase stimulation by IgG of patients with Graves' disease was erratic in two successive experiments, probably due to a non-specific effect of IgG. When adenyl cyclase stimulation was adopted as a sole indicator of thyroid stimulation, the results must be interpreted cautiously.", "contents": "[A comparison of various indicators of murine thyroid stimulation by LATS (author's transl)]. To obtain an in vitro method of LATS assay which is equally sensitive to a McKenzie bioassay, we compared the quality of cAMP generation-stimulation, thyroidal adenyl cyclase stimulation, and the stimulation of T3-release from mouse thyroid slices. Among those indicators of thyroid stimulation, stimulation by IgG of the release of T3 from incubated thyroid slices is the most sensitive, reproducible and reliable indicator, reflecting faithfully the results of a McKenzie bioassay. Stimulation of cAMP generation in slice manifested less sensitivity, but reasonable reproducibility. However, adenyl cyclase stimulation by IgG of patients with Graves' disease was erratic in two successive experiments, probably due to a non-specific effect of IgG. When adenyl cyclase stimulation was adopted as a sole indicator of thyroid stimulation, the results must be interpreted cautiously."}
{"id": "PMID:229004", "title": "Generalized eruptive histiocytoma. A case report with a review of the literature.", "content": "A case of generalized eruptive histiocytoma in a 52-year-old Indian male is described. This is probably the tenth case in the world and the first from this country. Histopathological features are discussed in detail and the literature is reviewed.", "contents": "Generalized eruptive histiocytoma. A case report with a review of the literature. A case of generalized eruptive histiocytoma in a 52-year-old Indian male is described. This is probably the tenth case in the world and the first from this country. Histopathological features are discussed in detail and the literature is reviewed."}
{"id": "PMID:229047", "title": "Parallel release of ACTH, beta-endorphin, alpha-MSH and beta-MSH-like immunoreactivities in rat anterior pituitary cells in culture.", "content": "Specific radioimmunoassays (RIAs) for ACTH, beta-endorphin, alpha-MSH and beta-MSH were used to identify the immunoreactive components released during incubation of rat anterior pituitary cells in primary culture. Such measurements were performed after separation of the incubation media by chromatography on Sephadex G-50 or G-75. The ACTH-RIA measured approximately equal amounts of 13 and 4.5K ACTH while equal proportions of components migrating at the position of beta-LPH and beta-endorphin were measured in the beta-endorphin RIA system. Immunoreactive components migrating at the position of gamma-LPH and alpha-MSH were measured in the beta-MSH and alpha-MSH RIA systems, resp. 3 purified corticotropin-releasing fractions (CRF) prepared from porcine hypothalami and increasing concentrations of N6,O2'-dibutyryl cyclic AMP and theophylline led to parallel release of ACTH, beta-endorphin, beta-MSH and alpha-MSH immunoreactivities while preincubation with dexamethasone led to a 30-60% inhibition of the release of all peptides. The present data show that the release of ACTH, beta-LPH, beta-endorphin, gamma-LPH and alpha-MSH-like immunoeactivities occurs in parallel in anterior pituitary cells in culture both under basal and acute stimulatory or inhibitory conditions of release.", "contents": "Parallel release of ACTH, beta-endorphin, alpha-MSH and beta-MSH-like immunoreactivities in rat anterior pituitary cells in culture. Specific radioimmunoassays (RIAs) for ACTH, beta-endorphin, alpha-MSH and beta-MSH were used to identify the immunoreactive components released during incubation of rat anterior pituitary cells in primary culture. Such measurements were performed after separation of the incubation media by chromatography on Sephadex G-50 or G-75. The ACTH-RIA measured approximately equal amounts of 13 and 4.5K ACTH while equal proportions of components migrating at the position of beta-LPH and beta-endorphin were measured in the beta-endorphin RIA system. Immunoreactive components migrating at the position of gamma-LPH and alpha-MSH were measured in the beta-MSH and alpha-MSH RIA systems, resp. 3 purified corticotropin-releasing fractions (CRF) prepared from porcine hypothalami and increasing concentrations of N6,O2'-dibutyryl cyclic AMP and theophylline led to parallel release of ACTH, beta-endorphin, beta-MSH and alpha-MSH immunoreactivities while preincubation with dexamethasone led to a 30-60% inhibition of the release of all peptides. The present data show that the release of ACTH, beta-LPH, beta-endorphin, gamma-LPH and alpha-MSH-like immunoeactivities occurs in parallel in anterior pituitary cells in culture both under basal and acute stimulatory or inhibitory conditions of release."}
{"id": "PMID:229048", "title": "Interaction between the hepatic growth hormone receptor and concanavalin A.", "content": "The interaction between the plant lectin concanavalin A (Con A) and hepatic receptors for human growth hormone (GH) has been studied in particulate and soluble microsomal membrane preparations from rabbit and rat liver. Con A shows a dose-dependent, partial (30%) inhibition of 125I-human GH binding which is reversed by the Con A competitor, alpha-methyl mannoside. The Con A effect is dependent on the receptor concentration. The inhibition by Con A in rabbit liver is a reflection of a decreased number of available binding sites--there is no effect on binding affinity. It would appear that Con A binds directly to the GH-binding protein and not to an adjacent membrane glycoprotein. The GH receptor may consist of more than one molecular species, differing only in the carbohydrate type or content.", "contents": "Interaction between the hepatic growth hormone receptor and concanavalin A. The interaction between the plant lectin concanavalin A (Con A) and hepatic receptors for human growth hormone (GH) has been studied in particulate and soluble microsomal membrane preparations from rabbit and rat liver. Con A shows a dose-dependent, partial (30%) inhibition of 125I-human GH binding which is reversed by the Con A competitor, alpha-methyl mannoside. The Con A effect is dependent on the receptor concentration. The inhibition by Con A in rabbit liver is a reflection of a decreased number of available binding sites--there is no effect on binding affinity. It would appear that Con A binds directly to the GH-binding protein and not to an adjacent membrane glycoprotein. The GH receptor may consist of more than one molecular species, differing only in the carbohydrate type or content."}
{"id": "PMID:229050", "title": "Chronic hyperinsulinemia in the fetal rhesus monkey: effects on hepatic enzymes active in lipogenesis and carbohydrate metabolism.", "content": "Hyperinsulinemia was produced in fetal rhesus monkeys for 21 days in the last third of gestation by subcutaneous pork insulin injected at 19 U a day. Plasma insulin concentrations in treated fetuses (N = 4) were 3525 microU/ml. There was no difference in paired pre- and post-treatment fetal plasma glucose concentration. Activity of the hepatic enzymes that promote glucose utilization (glucokinase and hexokinase) and glycolysis (phosphofructokinase, pyruvate kinase, and pyruvate dehydrogenase) was unaffected. Similarly, glycogen metabolism enzymes (active and inactive synthase and phosphorylase) were unaltered. Two gluconeogenic enzymes (PEPCK and glucose-6-phosphatase) were diminished in the treated group compared with controls. Fetal hyperinsulinemia enhanced lipogenic and NADPH-producing enzyme activities, as evidenced by a twofold increase in fatty acid synthase and in citrate cleavage enzyme activity. Malic enzyme was absent. Hyperinsulinemia with euglycemia (1) increases the activity of enzymes that participate in lipogenesis, (2) decreases some of those controlling gluconeogenesis, and (3) has no effect on the enzymes of glycolysis.", "contents": "Chronic hyperinsulinemia in the fetal rhesus monkey: effects on hepatic enzymes active in lipogenesis and carbohydrate metabolism. Hyperinsulinemia was produced in fetal rhesus monkeys for 21 days in the last third of gestation by subcutaneous pork insulin injected at 19 U a day. Plasma insulin concentrations in treated fetuses (N = 4) were 3525 microU/ml. There was no difference in paired pre- and post-treatment fetal plasma glucose concentration. Activity of the hepatic enzymes that promote glucose utilization (glucokinase and hexokinase) and glycolysis (phosphofructokinase, pyruvate kinase, and pyruvate dehydrogenase) was unaffected. Similarly, glycogen metabolism enzymes (active and inactive synthase and phosphorylase) were unaltered. Two gluconeogenic enzymes (PEPCK and glucose-6-phosphatase) were diminished in the treated group compared with controls. Fetal hyperinsulinemia enhanced lipogenic and NADPH-producing enzyme activities, as evidenced by a twofold increase in fatty acid synthase and in citrate cleavage enzyme activity. Malic enzyme was absent. Hyperinsulinemia with euglycemia (1) increases the activity of enzymes that participate in lipogenesis, (2) decreases some of those controlling gluconeogenesis, and (3) has no effect on the enzymes of glycolysis."}
{"id": "PMID:229051", "title": "Intracisternal A-particles in genetically diabetic mice: identification in pancreas and induction in cultured beta cells.", "content": "Sucrose density gradient analysis of purified pancreatic homogenates from glycaemic C57BL/Ks diabetes (db/db) mice and their normoglycaemic controls have revealed the presence in the diabetics of increased Mg++-dependent RNA-directed DNA polymerase activity sedimenting with a density of approximately 1.21 g/cm3. Electron microscopy revealed that this fraction contained typical intracisternal A-particles. Purified cultures of pancreatic islet cells 4--7 day old postnatal \"misty diabetic\" mice and normal siblings were established and then maintained in Eagle's minimal essential medium without serum. Under these conditions, the presence of intracisternal A-particles in beta cells of both mutant and control genotypes was very rare. No change in numbers of intracisternal A-particles was seen after 2--4 days of incubation in Dulbecco's-modified minimal essential medium containing 5.5 mmol/l glucose. However, when the glucose concentration of Dulbecco's medium was elevated to 16.5 mmol/l, ultrastructural changes specific to the beta cell population occurred that were reminiscent of those alterations observed in situ. Intracisternal A-particles were commonly seen in cultured beta cells showing hypersecretion-stress morphology. Since equal numbers of intracisternal A-particles were present in cultured beta cells from normal and mutant mice, it was concluded that the db gene itself was not required for intracisternal A-particle expression. The cell culture results suggest that elevated intracisternal A-particle activity observed in vivo may be produced directly or indirectly by the ambient high blood glucose levels characteristic of this mutant.", "contents": "Intracisternal A-particles in genetically diabetic mice: identification in pancreas and induction in cultured beta cells. Sucrose density gradient analysis of purified pancreatic homogenates from glycaemic C57BL/Ks diabetes (db/db) mice and their normoglycaemic controls have revealed the presence in the diabetics of increased Mg++-dependent RNA-directed DNA polymerase activity sedimenting with a density of approximately 1.21 g/cm3. Electron microscopy revealed that this fraction contained typical intracisternal A-particles. Purified cultures of pancreatic islet cells 4--7 day old postnatal \"misty diabetic\" mice and normal siblings were established and then maintained in Eagle's minimal essential medium without serum. Under these conditions, the presence of intracisternal A-particles in beta cells of both mutant and control genotypes was very rare. No change in numbers of intracisternal A-particles was seen after 2--4 days of incubation in Dulbecco's-modified minimal essential medium containing 5.5 mmol/l glucose. However, when the glucose concentration of Dulbecco's medium was elevated to 16.5 mmol/l, ultrastructural changes specific to the beta cell population occurred that were reminiscent of those alterations observed in situ. Intracisternal A-particles were commonly seen in cultured beta cells showing hypersecretion-stress morphology. Since equal numbers of intracisternal A-particles were present in cultured beta cells from normal and mutant mice, it was concluded that the db gene itself was not required for intracisternal A-particle expression. The cell culture results suggest that elevated intracisternal A-particle activity observed in vivo may be produced directly or indirectly by the ambient high blood glucose levels characteristic of this mutant."}
{"id": "PMID:229052", "title": "Acceleration of mammary cancer development by grafting of fetal mammary mesenchymes in C3H mice.", "content": "Transplantation of fetal mammary gland mesenchyme into mammary glands of 2-month-old syngeneic virgin mice resulted in focal re-enactment of events that normally occur probably during fetal and early postnatal development of the mammary gland. Portions of the recipient's mammary duct system in contact with the fetal mammary mesenchyme underwent branching and proliferation in a pattern resembling that of rudimentary mammary gland development. This process occurred in C3H mice regardless of whether or not the milk-transmitted mammary tumor virus (MTV-S) was present. In mice carrying MTV-S, mammary cancers of Types A and B appeared earlier and more frequently in the mammary glands that had received transplants of fetal mammary mesenchyme, compared with those in the glands that received no fetal mesenchyme. Some of the smaller cancers were shown to develop directly from portions of the mammary gland interacting with fetal mammary mesenchyme, without preformation of typical hyperplastic alveolar nodules. In C3H mice not carrying MTV-S, cancers did not appear in the similarly treated mammary glands. These facts suggest that non-hormonal and probably nonviral factors that stimulate focal proliferation in the mammary duct system resulting from transplantation of fetal mesenchymes eventually accelerate local development of mammary cancers.", "contents": "Acceleration of mammary cancer development by grafting of fetal mammary mesenchymes in C3H mice. Transplantation of fetal mammary gland mesenchyme into mammary glands of 2-month-old syngeneic virgin mice resulted in focal re-enactment of events that normally occur probably during fetal and early postnatal development of the mammary gland. Portions of the recipient's mammary duct system in contact with the fetal mammary mesenchyme underwent branching and proliferation in a pattern resembling that of rudimentary mammary gland development. This process occurred in C3H mice regardless of whether or not the milk-transmitted mammary tumor virus (MTV-S) was present. In mice carrying MTV-S, mammary cancers of Types A and B appeared earlier and more frequently in the mammary glands that had received transplants of fetal mammary mesenchyme, compared with those in the glands that received no fetal mesenchyme. Some of the smaller cancers were shown to develop directly from portions of the mammary gland interacting with fetal mammary mesenchyme, without preformation of typical hyperplastic alveolar nodules. In C3H mice not carrying MTV-S, cancers did not appear in the similarly treated mammary glands. These facts suggest that non-hormonal and probably nonviral factors that stimulate focal proliferation in the mammary duct system resulting from transplantation of fetal mesenchymes eventually accelerate local development of mammary cancers."}
{"id": "PMID:229053", "title": "Induction of tumor resistance in mice by L1210 leukemia cells persistently infected with HVJ (Sendai virus).", "content": "A temperature-sensitive strain of Sendai virus, HVJ-pi, showed little or no cytopathic effect and led to establishment of carrier cultures in several cell lines. By the use of this characteristic, L1210 leukemia cells persistently infected with HVJ-pi (L1210/c--HVJ-pi) was established, almost all of which were positively stained with fluorescent HVJ antibody. They are viable and grow almost equally as uninfected L1210 leukemia cells in vitro. Athymic nude mice (BALB/c, nu/nu), deficient of T-cells, died from intraperitoneal inoculation of L1210/c--HVJ-pi cells as well as by uninfected L1210 leukemia cells. However, viable L1210/c--HVJ-pi cells showed lower transplantability in normal syngeneic mice. This immunological mechanism of rejection was explained by the modification of cell surface membrane due to HVJ-pi infection. The mice which survived the inoculation of 10(5) L1210/c--HVJ-pi cells were able to reject 10(5) uninfected L1210 leukemia cells challenged subsequently. The induction of immune resistance was more prominent in (C57BL/6 x DBA/2)F1 mice or (BALB/c x DBA/2)F1 mice than in DBA/2 mice.", "contents": "Induction of tumor resistance in mice by L1210 leukemia cells persistently infected with HVJ (Sendai virus). A temperature-sensitive strain of Sendai virus, HVJ-pi, showed little or no cytopathic effect and led to establishment of carrier cultures in several cell lines. By the use of this characteristic, L1210 leukemia cells persistently infected with HVJ-pi (L1210/c--HVJ-pi) was established, almost all of which were positively stained with fluorescent HVJ antibody. They are viable and grow almost equally as uninfected L1210 leukemia cells in vitro. Athymic nude mice (BALB/c, nu/nu), deficient of T-cells, died from intraperitoneal inoculation of L1210/c--HVJ-pi cells as well as by uninfected L1210 leukemia cells. However, viable L1210/c--HVJ-pi cells showed lower transplantability in normal syngeneic mice. This immunological mechanism of rejection was explained by the modification of cell surface membrane due to HVJ-pi infection. The mice which survived the inoculation of 10(5) L1210/c--HVJ-pi cells were able to reject 10(5) uninfected L1210 leukemia cells challenged subsequently. The induction of immune resistance was more prominent in (C57BL/6 x DBA/2)F1 mice or (BALB/c x DBA/2)F1 mice than in DBA/2 mice."}
{"id": "PMID:229054", "title": "Cytostatic activity of peripheral blood monocytes against bronchogenic carcinoma cells in patients with lung cancer.", "content": "Cytostatic acitivity of peripheral blood monocytes against cultured cell lines of bronchogenic carcinoma was examined in patients with lung cancer. Cytostatic activity in lung cancer patients with neither augmented nor suppressed as compared with that of controls such as normal healthy persons, patients with malignancies other than lung cancer, and patients with benign respiratory diseases. There was no correlation between the cytostatic activity of monocytes and the advance of clinical stages of the disease. Conventional modalities of anticancer treatments such as surgery, radiotherapy, chemotherapy, and their combination therapy had no effect on cytostatic activity of peripheral blood monocytes. However, adequate immunotherapy with nocardia rubra cell-wall skeleton augmented the cytostatic activity of peripheral blood monocytes, although adequate immunotherapy with Mycobacterium bovis BCG cell-wall skeleton had no effect.", "contents": "Cytostatic activity of peripheral blood monocytes against bronchogenic carcinoma cells in patients with lung cancer. Cytostatic acitivity of peripheral blood monocytes against cultured cell lines of bronchogenic carcinoma was examined in patients with lung cancer. Cytostatic activity in lung cancer patients with neither augmented nor suppressed as compared with that of controls such as normal healthy persons, patients with malignancies other than lung cancer, and patients with benign respiratory diseases. There was no correlation between the cytostatic activity of monocytes and the advance of clinical stages of the disease. Conventional modalities of anticancer treatments such as surgery, radiotherapy, chemotherapy, and their combination therapy had no effect on cytostatic activity of peripheral blood monocytes. However, adequate immunotherapy with nocardia rubra cell-wall skeleton augmented the cytostatic activity of peripheral blood monocytes, although adequate immunotherapy with Mycobacterium bovis BCG cell-wall skeleton had no effect."}
{"id": "PMID:229055", "title": "Lack of participation of murine myeloma cells in the fusion of cocultured XC cells.", "content": "Electron microscopy of thin sections of syncytia, formed by fusion of homologous XC cells, clarified that these heterologous cells were simply invaginated by syncytia and that they were clearly separated by the limiting cytoplasmic membranes. The C particles found at the boundary showed no sign of connection with the surrounding syncytial cell membrane, while some were seen budding from the surface of the producer cells. These results strongly suggest that the XC cells, even when cocultured with the C-type virus-producing myeloma cells, fuse homologously among themselves, and the virus-producing heterologous cells do not participate in the event.", "contents": "Lack of participation of murine myeloma cells in the fusion of cocultured XC cells. Electron microscopy of thin sections of syncytia, formed by fusion of homologous XC cells, clarified that these heterologous cells were simply invaginated by syncytia and that they were clearly separated by the limiting cytoplasmic membranes. The C particles found at the boundary showed no sign of connection with the surrounding syncytial cell membrane, while some were seen budding from the surface of the producer cells. These results strongly suggest that the XC cells, even when cocultured with the C-type virus-producing myeloma cells, fuse homologously among themselves, and the virus-producing heterologous cells do not participate in the event."}
{"id": "PMID:229056", "title": "In vivo enhancement of general and specific transcription in Escherichia coli by DNA gyrase activity.", "content": "The effect of drugs which inhibit DNA gyrase, including nalidixic acid, oxolinic acid and coumerycin, on transcription of Escherichia coli bacteria, phage and plasmid genomes was studied. Quantitative estimates of the synthesis of RNA under drug-treatment conditions showed that synthesis of many RNA species, including trp mRNA, was subject to inhibiton by the drug. Transcription directed by the lambda promoter pR was selectively less sensitive to the drug action than transcription initiated at the lambda promoter pL. Evidence was obtained showing that diminished transcription resulted from less frequent RNA chain initiation rather than a premature arrest of the chain elongation. Inhibiton of transcription by these DNA gyrase inhibitors was observed even in the absence of DNA replication. The inhibition by oxolinic acid or coumerycin was not observed in an E. coli strain bearing a nalAr mutation or a cour mutation, respectively. The reduction of trp mRNA synthesis in oxolinic acid-treated cells cannot be attributed to the increase in the rate of nascent mRNA degradation. These results indicate that DNA gyrase is generally required for intracellular RNA synthesis, and suggest that the supercoiling of DNA by this winding enzyme enhances the initiation of transcription.", "contents": "In vivo enhancement of general and specific transcription in Escherichia coli by DNA gyrase activity. The effect of drugs which inhibit DNA gyrase, including nalidixic acid, oxolinic acid and coumerycin, on transcription of Escherichia coli bacteria, phage and plasmid genomes was studied. Quantitative estimates of the synthesis of RNA under drug-treatment conditions showed that synthesis of many RNA species, including trp mRNA, was subject to inhibiton by the drug. Transcription directed by the lambda promoter pR was selectively less sensitive to the drug action than transcription initiated at the lambda promoter pL. Evidence was obtained showing that diminished transcription resulted from less frequent RNA chain initiation rather than a premature arrest of the chain elongation. Inhibiton of transcription by these DNA gyrase inhibitors was observed even in the absence of DNA replication. The inhibition by oxolinic acid or coumerycin was not observed in an E. coli strain bearing a nalAr mutation or a cour mutation, respectively. The reduction of trp mRNA synthesis in oxolinic acid-treated cells cannot be attributed to the increase in the rate of nascent mRNA degradation. These results indicate that DNA gyrase is generally required for intracellular RNA synthesis, and suggest that the supercoiling of DNA by this winding enzyme enhances the initiation of transcription."}
{"id": "PMID:229061", "title": "Injury to cultured endothelial cells: the role of lipoproteins and thrombo-active agents.", "content": "Thrombin and low density lipoproteins (LDL) are capable of inducing damage to human endothelial cells in primary culture. These substances both induce endothelial contraction as first recognizable morphological change. However, the effect of thrombin appeared early, was reversible and prevented by hirudin, while LDL acted over hours and the injury was progressive. Addition and high density lipoprotein (HDL), together with LDL, inhibited the cellular injury induced by LDL.", "contents": "Injury to cultured endothelial cells: the role of lipoproteins and thrombo-active agents. Thrombin and low density lipoproteins (LDL) are capable of inducing damage to human endothelial cells in primary culture. These substances both induce endothelial contraction as first recognizable morphological change. However, the effect of thrombin appeared early, was reversible and prevented by hirudin, while LDL acted over hours and the injury was progressive. Addition and high density lipoprotein (HDL), together with LDL, inhibited the cellular injury induced by LDL."}
{"id": "PMID:229062", "title": "Modulation of platelet function by prostaglandins: characterization of platelet receptors for stimulatory prostaglandins and the role of arachidonate metabolites in platelet degranulation responses.", "content": "The effects of PGG2 and PGH2 on platelets are mimicked by synthetic PG analogues in which the nature and specificity of the substituents on carbons 11 and 15 (or 16) are important determinants of reactivity. Arachidonic acid and stimulatory PGs induce secretion of platelet dense granule and alpha granule constituents, but not lysomal constituents, although arachidonate metabolism is necessary for collagen-induced release of lysosomal enzymes. NO164 acts on platelets as an endoperoxide antagonist: Trimethoquinol acts as an endoperoxide and TxA2 antagonist. PGs induce platelet aggregation by combining with a specific (endoperoxide) receptor.", "contents": "Modulation of platelet function by prostaglandins: characterization of platelet receptors for stimulatory prostaglandins and the role of arachidonate metabolites in platelet degranulation responses. The effects of PGG2 and PGH2 on platelets are mimicked by synthetic PG analogues in which the nature and specificity of the substituents on carbons 11 and 15 (or 16) are important determinants of reactivity. Arachidonic acid and stimulatory PGs induce secretion of platelet dense granule and alpha granule constituents, but not lysomal constituents, although arachidonate metabolism is necessary for collagen-induced release of lysosomal enzymes. NO164 acts on platelets as an endoperoxide antagonist: Trimethoquinol acts as an endoperoxide and TxA2 antagonist. PGs induce platelet aggregation by combining with a specific (endoperoxide) receptor."}
{"id": "PMID:229063", "title": "The estimation of alcohol dehydrogenase activity in aerobic and anaerobic \"permeabilised\" baker's yeast cells.", "content": "The in vivo and in vitro activity of alcohol dehydrogenase from baker's yeast maintained under aerobic and anaerobic conditions was measured. In vivo measurements were made in cells \"permeabilised\" with toluene. Michaelis constants (NAD+ as substrate) were found to be almost identical as those reported for purified preparations. In addition the Km of the enzyme from cells incubated under anaerobic conditions was virtually identical to that from cells from aerobic conditions. The activity of the enzyme was found to be greater (in both \"permeabilised\" cells and extracts) in cells maintained under nitrogen than air. Cells metabolizing glucose in N2 produced greater levels of ethanol than in air and the rate of NAD+ reduction was also found to be greater in N2 than in air. The results indicate that it was feasible to determine rates of this enzyme in vivo and that the difference in activity of alcohol dehydrogenase under N2 and air may conceivably account for differences in rates of glucose utilisation, ethanol production and NAD+ reduction in air and nitrogen.", "contents": "The estimation of alcohol dehydrogenase activity in aerobic and anaerobic \"permeabilised\" baker's yeast cells. The in vivo and in vitro activity of alcohol dehydrogenase from baker's yeast maintained under aerobic and anaerobic conditions was measured. In vivo measurements were made in cells \"permeabilised\" with toluene. Michaelis constants (NAD+ as substrate) were found to be almost identical as those reported for purified preparations. In addition the Km of the enzyme from cells incubated under anaerobic conditions was virtually identical to that from cells from aerobic conditions. The activity of the enzyme was found to be greater (in both \"permeabilised\" cells and extracts) in cells maintained under nitrogen than air. Cells metabolizing glucose in N2 produced greater levels of ethanol than in air and the rate of NAD+ reduction was also found to be greater in N2 than in air. The results indicate that it was feasible to determine rates of this enzyme in vivo and that the difference in activity of alcohol dehydrogenase under N2 and air may conceivably account for differences in rates of glucose utilisation, ethanol production and NAD+ reduction in air and nitrogen."}
{"id": "PMID:229066", "title": "Studies on cytochrome c oxidase, VII. Isolation and chemical characterization of polypeptide VII.", "content": "Polypeptide VII of cytochrome c oxidase was isolated and purified by gel filtration on Bio-Gel P-10 in 10% acetic acid. Automatic Edman degradation of this peptide chain was not successful, because it is blocked at the N-terminus. The amino acid analysis shows a relatively high content of hydrophilic residues (54%). On the basis of this analysis and the apparent molecular weight by sodium dodecyl sulfate gel electrophoresis and gel filtration, a chain length of about 80 residues was calculated. Among the tryptic peptides one blocked heptapeptide was found. Cleavage of this peptide with thermolysin gave two peptide fragments, one of which was not retained on a cation exchange resin. Mass spectrometric sequence determination of this peptide revealed the structure Ac-Ala-Glu-Asp for the N-terminus of polypeptide VII. Treatment with carboxypeptidase A at two different pH values showed that the C-terminal amino acid is isoleucine and the penultimate amino acid is lysine.", "contents": "Studies on cytochrome c oxidase, VII. Isolation and chemical characterization of polypeptide VII. Polypeptide VII of cytochrome c oxidase was isolated and purified by gel filtration on Bio-Gel P-10 in 10% acetic acid. Automatic Edman degradation of this peptide chain was not successful, because it is blocked at the N-terminus. The amino acid analysis shows a relatively high content of hydrophilic residues (54%). On the basis of this analysis and the apparent molecular weight by sodium dodecyl sulfate gel electrophoresis and gel filtration, a chain length of about 80 residues was calculated. Among the tryptic peptides one blocked heptapeptide was found. Cleavage of this peptide with thermolysin gave two peptide fragments, one of which was not retained on a cation exchange resin. Mass spectrometric sequence determination of this peptide revealed the structure Ac-Ala-Glu-Asp for the N-terminus of polypeptide VII. Treatment with carboxypeptidase A at two different pH values showed that the C-terminal amino acid is isoleucine and the penultimate amino acid is lysine."}
{"id": "PMID:229067", "title": "Studies on cytochrome c oxidase, VIII. The amino acid sequence of polypeptide VII.", "content": "The sequence determination of polypeptide VII from beef heart cytochrome c oxidase is described. The amino acid sequence is deduced from overlapping tryptic peptides and peptides obtained after cleavage with Staphylococcus aureus protease. The protein consists of 85 amino acids corresponding to a Mr of 10026, in agreement with a value of 9500 obtained by sodium dodecyl sulfate gel electrophoresis. The amino acid sequence around the only methionine present is very similar to sequences around the invariant heme binding methionine of the cytochrome c family. This similarity suggests that the protein is one of the heme bindings subunits of the oxidase.", "contents": "Studies on cytochrome c oxidase, VIII. The amino acid sequence of polypeptide VII. The sequence determination of polypeptide VII from beef heart cytochrome c oxidase is described. The amino acid sequence is deduced from overlapping tryptic peptides and peptides obtained after cleavage with Staphylococcus aureus protease. The protein consists of 85 amino acids corresponding to a Mr of 10026, in agreement with a value of 9500 obtained by sodium dodecyl sulfate gel electrophoresis. The amino acid sequence around the only methionine present is very similar to sequences around the invariant heme binding methionine of the cytochrome c family. This similarity suggests that the protein is one of the heme bindings subunits of the oxidase."}
{"id": "PMID:229068", "title": "Studies on the protein composition of human serum very low density lipoproteins: demonstration of the beta 2-glycoprotein-I.", "content": "Human serum VLDL isolated by polyanion precipitation and ultracentrifugation have been delipidated with ethanal/diethyl ether. By electrophoresis in 10% polyacrylamide gels containing 8M urea, we found a protein which comigrated with apolipoprotein E. This protein was purified by column chromatography and turned out to be identical with beta 2-glycoprotein-I, the serum factor which is necessary for the precipitation of triglyceride-rich lipoproteins with sodium decyl sulfate or sodium dodecyl sulfate. Upon analytical isoelectric focusing, beta 2-glycoprotein-I gave four major bands in the pH region 5.7--6.6. All four bands gave an immunochemical reaction of identity with a monospecific antiserum. From its unique amino acid composition we conclude that beta 2-glycoprotein-I is distinct from all apolipoproteins described previously in the literature.", "contents": "Studies on the protein composition of human serum very low density lipoproteins: demonstration of the beta 2-glycoprotein-I. Human serum VLDL isolated by polyanion precipitation and ultracentrifugation have been delipidated with ethanal/diethyl ether. By electrophoresis in 10% polyacrylamide gels containing 8M urea, we found a protein which comigrated with apolipoprotein E. This protein was purified by column chromatography and turned out to be identical with beta 2-glycoprotein-I, the serum factor which is necessary for the precipitation of triglyceride-rich lipoproteins with sodium decyl sulfate or sodium dodecyl sulfate. Upon analytical isoelectric focusing, beta 2-glycoprotein-I gave four major bands in the pH region 5.7--6.6. All four bands gave an immunochemical reaction of identity with a monospecific antiserum. From its unique amino acid composition we conclude that beta 2-glycoprotein-I is distinct from all apolipoproteins described previously in the literature."}
{"id": "PMID:229069", "title": "Covalent binding of photosensitive 1-(12-azido-[9,10(-3)H2]oleoyl)glycero-3-phosphocholine (lysolecithin) to human serum high density apolipoproteins.", "content": "Human serum high density apoproteins were complexed with increasing concentrations of 1-(12-azido-[9,10(-3)H2]oleoyl)glycero-3-phosphocholine up to the saturation concentration (72 mol lysolecithin per mol apo HDL). Ultraviolet irradiation generated the nitrene which led to crosslinking with the two main apolipoproteins AI and AII. Methods are described for the removal of excess, unbound lipid and the column chromatographic separation of the lipopolypeptides AI and AII.", "contents": "Covalent binding of photosensitive 1-(12-azido-[9,10(-3)H2]oleoyl)glycero-3-phosphocholine (lysolecithin) to human serum high density apolipoproteins. Human serum high density apoproteins were complexed with increasing concentrations of 1-(12-azido-[9,10(-3)H2]oleoyl)glycero-3-phosphocholine up to the saturation concentration (72 mol lysolecithin per mol apo HDL). Ultraviolet irradiation generated the nitrene which led to crosslinking with the two main apolipoproteins AI and AII. Methods are described for the removal of excess, unbound lipid and the column chromatographic separation of the lipopolypeptides AI and AII."}
{"id": "PMID:229071", "title": "An appraisal of the relationship between primary hepatocellular carcinoma and hepatitis B virus.", "content": "The association between hepatitis B virus infection and primary hepatocellular carcinoma is reviewed. On the basis of serological and tissue examination there is a close link between virus infection and the tumour. While there is evidence to favour an oncogenic role for virus this is not conclusive, and other possible explanations for the relationship are discussed.", "contents": "An appraisal of the relationship between primary hepatocellular carcinoma and hepatitis B virus. The association between hepatitis B virus infection and primary hepatocellular carcinoma is reviewed. On the basis of serological and tissue examination there is a close link between virus infection and the tumour. While there is evidence to favour an oncogenic role for virus this is not conclusive, and other possible explanations for the relationship are discussed."}
{"id": "PMID:229072", "title": "Invasive lobular carcinoma of the breast: incidence and variants.", "content": "The criteria for the separation of invasive lobular and ductal carcinomas are analysed. Lobular tumours account for 14% of invasive cancers in our material. The widely differing figures given in the literature are mainly attributable to intrinsic difficulties of classification. In addition to the classical dissociated-cell patterns with single filing, a tragetoid appearance and related features, variants with trabecular, loose alveolar and tubular features are recognized; a 'solid' variant requires further investigation. The variants either represent better differentiated forms, or in some cases, an 'earlier' phase in the production of the more traditional Indian file formations and dartboard patterns. Focal signet-ring cell differentiation is another newly-recognized feature. The theoretical and practical implications of these variants are considered. The division into invasive lobular and ductal carcinomas is not as easy as most of the literature implies. Five per cent of cases could not be so classified and, in some of these unclassified cases, both ductal and lobular differentiation may be present. In the diagnosis of problem cases, no single parameter proved reliable but a combination of several parameters enables one to make an objective diagnosis in about 95% of cases.", "contents": "Invasive lobular carcinoma of the breast: incidence and variants. The criteria for the separation of invasive lobular and ductal carcinomas are analysed. Lobular tumours account for 14% of invasive cancers in our material. The widely differing figures given in the literature are mainly attributable to intrinsic difficulties of classification. In addition to the classical dissociated-cell patterns with single filing, a tragetoid appearance and related features, variants with trabecular, loose alveolar and tubular features are recognized; a 'solid' variant requires further investigation. The variants either represent better differentiated forms, or in some cases, an 'earlier' phase in the production of the more traditional Indian file formations and dartboard patterns. Focal signet-ring cell differentiation is another newly-recognized feature. The theoretical and practical implications of these variants are considered. The division into invasive lobular and ductal carcinomas is not as easy as most of the literature implies. Five per cent of cases could not be so classified and, in some of these unclassified cases, both ductal and lobular differentiation may be present. In the diagnosis of problem cases, no single parameter proved reliable but a combination of several parameters enables one to make an objective diagnosis in about 95% of cases."}
{"id": "PMID:229073", "title": "Paneth cell-rich papillary adenocarcinoma and a mucoid adenocarcinoma occurring synchronously in colon: a light and electron microscopic study.", "content": "A 71-year-old man who presented with iron deficiency anaemia and weight loss was found to have two colonic tumours: a mucoid adenocarcinoma at the splenic flexure and a papillary adenocarcinoma rich in Paneth cells in the ascending colon. The light and ultrastructural features of the neoplastic cells are described, and the significant of the presence of neoplastic Paneth cells is discussed.", "contents": "Paneth cell-rich papillary adenocarcinoma and a mucoid adenocarcinoma occurring synchronously in colon: a light and electron microscopic study. A 71-year-old man who presented with iron deficiency anaemia and weight loss was found to have two colonic tumours: a mucoid adenocarcinoma at the splenic flexure and a papillary adenocarcinoma rich in Paneth cells in the ascending colon. The light and ultrastructural features of the neoplastic cells are described, and the significant of the presence of neoplastic Paneth cells is discussed."}
{"id": "PMID:229074", "title": "[Localization of the gene for phosphoglycolate phosphatase (PGP) on the chromosome 16 by interspecific hybridization (author's transl)].", "content": "Eight primary man-mouse (C11D/TK-) hybrids, twenty three primary and seven secondary man-hamster (CH/HGPRT-) were analyzed for human phosphoglycolate phosphatase (PGP) and for human chromosomes. The following results were obtained: 1. A positive correlation is observed between the chromosome 16 and PGP. 15 hybrids are chr.16+PGP+, 14 hybrids are chr.16-PGP- and 4 hybrids are chr.16-PGP+. 2. The percentage of dissociation between PGP and the chr.16 is low (12%) in comparison with the high percentage of dissociation between PGP and the other autosomes (between 37% and 65%). 3. Excepted the chromosome 16, the other autosomes are observed in hybrids PGP-. These different results indicate the localization of the gene for human PGP on the chromosome 16. The dissociation results chr.16-PGP+ are explained by the breakage of the chr.16 in the hybrids.", "contents": "[Localization of the gene for phosphoglycolate phosphatase (PGP) on the chromosome 16 by interspecific hybridization (author's transl)]. Eight primary man-mouse (C11D/TK-) hybrids, twenty three primary and seven secondary man-hamster (CH/HGPRT-) were analyzed for human phosphoglycolate phosphatase (PGP) and for human chromosomes. The following results were obtained: 1. A positive correlation is observed between the chromosome 16 and PGP. 15 hybrids are chr.16+PGP+, 14 hybrids are chr.16-PGP- and 4 hybrids are chr.16-PGP+. 2. The percentage of dissociation between PGP and the chr.16 is low (12%) in comparison with the high percentage of dissociation between PGP and the other autosomes (between 37% and 65%). 3. Excepted the chromosome 16, the other autosomes are observed in hybrids PGP-. These different results indicate the localization of the gene for human PGP on the chromosome 16. The dissociation results chr.16-PGP+ are explained by the breakage of the chr.16 in the hybrids."}
{"id": "PMID:229075", "title": "Non-specific effects of avian retrovirus co-incubation on lymphocyte function: abrogation of antigen- and mitogen-induced proliferative responsiveness.", "content": "Peripheral blood lymphocytes from chickens bearing tumours induced by avian retroviruses can be stimulated to divide by group-specific antigens present in supernatant fluids of avian retrovirus-infected but not normal chicken embryo fibroblast (CEF) cells. Centrifugation studies revealed that the relevant antigenic activity is non-virion in nature. Indeed, the presence of avian retrovirus particles was found to be inhibitory to the capacity of sensitized lymphocytes to be stimulated in this antigen-driven blastogenesis assay. Similar results were obtained in lymphocyte mitogenesis experiments in which any of peripheral chicken lymphocytes or mouse splenic, lymph node or thymic lymphocytes were co-incubated with either concanavalin A or phytohaemagglutinin in the presence of numerous types of virus particles. This inhibitory effect was not due to infection of lymphocytes by the viruses tested, and was obtained in the case of lymphocyte-virus combinations for which the cells lacked the surface receptors required for viral entry. Virus could be added to lymphocyte cultures as late as 26 h after co-incubation with mitogen, and still inhibit the usual mitogenic response. In addition, co-addition of virus to lymphocytes in the presence of concanavalin A was found to block the capping of ligand-bound receptors which normally ensues. Pre-added virus did not, however, affect the ability of lectins to bind to cells.", "contents": "Non-specific effects of avian retrovirus co-incubation on lymphocyte function: abrogation of antigen- and mitogen-induced proliferative responsiveness. Peripheral blood lymphocytes from chickens bearing tumours induced by avian retroviruses can be stimulated to divide by group-specific antigens present in supernatant fluids of avian retrovirus-infected but not normal chicken embryo fibroblast (CEF) cells. Centrifugation studies revealed that the relevant antigenic activity is non-virion in nature. Indeed, the presence of avian retrovirus particles was found to be inhibitory to the capacity of sensitized lymphocytes to be stimulated in this antigen-driven blastogenesis assay. Similar results were obtained in lymphocyte mitogenesis experiments in which any of peripheral chicken lymphocytes or mouse splenic, lymph node or thymic lymphocytes were co-incubated with either concanavalin A or phytohaemagglutinin in the presence of numerous types of virus particles. This inhibitory effect was not due to infection of lymphocytes by the viruses tested, and was obtained in the case of lymphocyte-virus combinations for which the cells lacked the surface receptors required for viral entry. Virus could be added to lymphocyte cultures as late as 26 h after co-incubation with mitogen, and still inhibit the usual mitogenic response. In addition, co-addition of virus to lymphocytes in the presence of concanavalin A was found to block the capping of ligand-bound receptors which normally ensues. Pre-added virus did not, however, affect the ability of lectins to bind to cells."}
{"id": "PMID:229078", "title": "Effect of leukocyte hydrolases on bacteria. XIII. Role played by leukocyte extracts, lysolecithin, phospholipase a2, lysozyme, cationic proteins, and detergents in the solubilization of lipids from Staphylococcus aureus and group A streptococci: relation to bactericidal and bacteriolytic reactions in inflammatory sites.", "content": "The bactericidal and bacteriolytic effects of lysolecithin (LL) and egg-white lysozyme (LYZ) on Staph. aureus and group A streptococci and the solubilization of phospholipids from the bacterial membranes by these agents was studied. Low concentrations of lysolecithin (1--10 microgrames/ml) are highly bactericidal for Steph. aureus and group A streptococci, but induce neither bacteriolysis nor solubilization of a substantial amount of membrane phospholipids. On the other hand, while LL at greater than 50 micrograms/ml causes substantial lipid release, a combination of LL and LYZ is absolutely needed to solubilize lipids from streptococci. This combination is, however, not bacteriolytic for this microrganism. The solubilization of lipids from staphylococci by LL is much faster than that induced in streptococci by LL + LYZ. The solubilization of the bulk of membrane lipids from staphylococci can also be achieved by Triton X-100 and by sodium lauryl sulfate and from group A streptococci by Triton X-100 plus LYZ. A variety of other detergents (e.g., Cetavlon, sodium taurocholate, cetyl pyrdinium chloride) have no lipid-releasing properties even in the presence of LYZ. The release of lipids by LYZ (in the presence of LL) from group A streptococci is related to its enzymatic activity, on a still unknown substrate, but not to its cationic nature as this muramidase cannot be replaced by a variety of cation substances (histone, polylysin, leukocyte cationic proteins, polymyxin B, and spermidine). The release of lipids from staphylococci by LL is not inhibited by a variety of anionic and cationic polyelectrocytes (heparin, liquoid, chondroitin sulfate, DNA histone, and polylysine) which markedly inhibit the release of lipids from group A streptococci by LL and LYZ. Streptococci that had been cultivated in the presence of subinhibitory concentrations of penicillin G lose their membrane phospholipids to a larger extent and by much smaller concentrations of LL and LYZ, as compared to controls, suggesting that the interference with the synthesis of the peptidoglycan increases the accessibility of the cell membrane to the lipid-releasing agents. The mechanism by which LL collaborates with LYZ in lipid release is still not known. The possible role of bacterial lipids and lyso compounds in the control of bacterial survival in inflammatory sites is briefly discussed.", "contents": "Effect of leukocyte hydrolases on bacteria. XIII. Role played by leukocyte extracts, lysolecithin, phospholipase a2, lysozyme, cationic proteins, and detergents in the solubilization of lipids from Staphylococcus aureus and group A streptococci: relation to bactericidal and bacteriolytic reactions in inflammatory sites. The bactericidal and bacteriolytic effects of lysolecithin (LL) and egg-white lysozyme (LYZ) on Staph. aureus and group A streptococci and the solubilization of phospholipids from the bacterial membranes by these agents was studied. Low concentrations of lysolecithin (1--10 microgrames/ml) are highly bactericidal for Steph. aureus and group A streptococci, but induce neither bacteriolysis nor solubilization of a substantial amount of membrane phospholipids. On the other hand, while LL at greater than 50 micrograms/ml causes substantial lipid release, a combination of LL and LYZ is absolutely needed to solubilize lipids from streptococci. This combination is, however, not bacteriolytic for this microrganism. The solubilization of lipids from staphylococci by LL is much faster than that induced in streptococci by LL + LYZ. The solubilization of the bulk of membrane lipids from staphylococci can also be achieved by Triton X-100 and by sodium lauryl sulfate and from group A streptococci by Triton X-100 plus LYZ. A variety of other detergents (e.g., Cetavlon, sodium taurocholate, cetyl pyrdinium chloride) have no lipid-releasing properties even in the presence of LYZ. The release of lipids by LYZ (in the presence of LL) from group A streptococci is related to its enzymatic activity, on a still unknown substrate, but not to its cationic nature as this muramidase cannot be replaced by a variety of cation substances (histone, polylysin, leukocyte cationic proteins, polymyxin B, and spermidine). The release of lipids from staphylococci by LL is not inhibited by a variety of anionic and cationic polyelectrocytes (heparin, liquoid, chondroitin sulfate, DNA histone, and polylysine) which markedly inhibit the release of lipids from group A streptococci by LL and LYZ. Streptococci that had been cultivated in the presence of subinhibitory concentrations of penicillin G lose their membrane phospholipids to a larger extent and by much smaller concentrations of LL and LYZ, as compared to controls, suggesting that the interference with the synthesis of the peptidoglycan increases the accessibility of the cell membrane to the lipid-releasing agents. The mechanism by which LL collaborates with LYZ in lipid release is still not known. The possible role of bacterial lipids and lyso compounds in the control of bacterial survival in inflammatory sites is briefly discussed."}
{"id": "PMID:229079", "title": "Effects of subinhibitory amounts of ampicillin, amoxycillin and mecillinam on the adhesion of Escherichia coli bacteria to human urinary tract epithelial cells: a preliminary study.", "content": "Attachment to mucous surfaces may be a prerequisite for bacteria colonizing these surfaces or invading underlying tissues. Subinhibitory amounts of ampicillin and amoxycillin but not mecillinam decreased the attachment of Escherichia coli bacteria to human uro-epithelial cells in vitro. No significant synergistic effect on the attachment by the antibiotics was obtained. The present report indicates a new parameter for the study of antibacterial actions of drugs.", "contents": "Effects of subinhibitory amounts of ampicillin, amoxycillin and mecillinam on the adhesion of Escherichia coli bacteria to human urinary tract epithelial cells: a preliminary study. Attachment to mucous surfaces may be a prerequisite for bacteria colonizing these surfaces or invading underlying tissues. Subinhibitory amounts of ampicillin and amoxycillin but not mecillinam decreased the attachment of Escherichia coli bacteria to human uro-epithelial cells in vitro. No significant synergistic effect on the attachment by the antibiotics was obtained. The present report indicates a new parameter for the study of antibacterial actions of drugs."}
{"id": "PMID:229083", "title": "Angiotensin-converting enzyme in sarcoid uveitis.", "content": "The diagnosis of ocular sarcoid is presumptive in the absence of systemic disease. The association of elevated serum angiotensin-converting enzyme (ACE) levels with active systemic sarcoid has been well described. With a sensitive fluorimetric assay for ACE, we found that five of ten chronic granulomatous uveitis patients without systemic sarcoid had elevated serum ACE levels. None of ten patients with uveitis of known etiology had elevated serum ACE levels. We believe that the association of an elevated serum ACE level with chronic granulomatous uveitis suggests the diagnosis of ocular sarcoid.", "contents": "Angiotensin-converting enzyme in sarcoid uveitis. The diagnosis of ocular sarcoid is presumptive in the absence of systemic disease. The association of elevated serum angiotensin-converting enzyme (ACE) levels with active systemic sarcoid has been well described. With a sensitive fluorimetric assay for ACE, we found that five of ten chronic granulomatous uveitis patients without systemic sarcoid had elevated serum ACE levels. None of ten patients with uveitis of known etiology had elevated serum ACE levels. We believe that the association of an elevated serum ACE level with chronic granulomatous uveitis suggests the diagnosis of ocular sarcoid."}
{"id": "PMID:229084", "title": "Etiology of acute gastroenteritis in children in Israel: role of human reoviruslike agent and bacterial pathogens.", "content": "A study of acute gastroenteritis in children was carried out with the aim of establishing the prevalence of human reoviruslike agent (HRLA) and its relation to other enteric pathogens in Israel. The stools of 384 children with acute diarrhea referred to a pediatric emergency service were screened for HRLA by counterimmunoelectroosmorphoresis (CIEOP) and for pathogenic bacteria. Evidence of HRLA infection was found in 65 patients (17%). The highest infection rate prevailed during the cool season (25%), with a peak prevalence (41%) in November, when both the temperature and humidity were low. A very high proportion of HRLA was found in children younger than 36 months and no HRLA infection was observed in those older than nine years. The highest prevalence occurred in infants younger than six months, a situation rarely encountered in other countries. The main clinical features of HRLA infection were fever, vomiting, dehydration, signs of upper respiratory infection and carbohydrate intolerance. Bacterial pathogens accounted for 45% of enteric infections. Shigella species predominated (28%) during the summer season, especially in older children. In 38% of the study group, no etiologic agent could be detected. None of the 50 control subjects showed evidence of viral or bacterial pathogens in stools.", "contents": "Etiology of acute gastroenteritis in children in Israel: role of human reoviruslike agent and bacterial pathogens. A study of acute gastroenteritis in children was carried out with the aim of establishing the prevalence of human reoviruslike agent (HRLA) and its relation to other enteric pathogens in Israel. The stools of 384 children with acute diarrhea referred to a pediatric emergency service were screened for HRLA by counterimmunoelectroosmorphoresis (CIEOP) and for pathogenic bacteria. Evidence of HRLA infection was found in 65 patients (17%). The highest infection rate prevailed during the cool season (25%), with a peak prevalence (41%) in November, when both the temperature and humidity were low. A very high proportion of HRLA was found in children younger than 36 months and no HRLA infection was observed in those older than nine years. The highest prevalence occurred in infants younger than six months, a situation rarely encountered in other countries. The main clinical features of HRLA infection were fever, vomiting, dehydration, signs of upper respiratory infection and carbohydrate intolerance. Bacterial pathogens accounted for 45% of enteric infections. Shigella species predominated (28%) during the summer season, especially in older children. In 38% of the study group, no etiologic agent could be detected. None of the 50 control subjects showed evidence of viral or bacterial pathogens in stools."}
{"id": "PMID:229087", "title": "[New developments relating to papillomaviruses].", "content": "Molecular hybridization technique and immunofluorescence studies with use of specific immune sera against the purified virions isolated from various types of warts and wart-like lesions of epidermodysplasia verruciformis (EV) made it possible to detect four different types of human papilloma viruses (HPV). The recognition of the viruses is important because of the different morphology of the lesions induced and their various oncogenic potentials. HPV1 is mainly responsible for plantar warts, HPV2 for common (hand) warts, HPV3 has been found both in flat warts and in the variety of EV in which skin lesions are of flat wart type, the course is relatively more benign, and usually malignant transformation is not to be expected. HPV4 was up to now found exclusively in the cases of EV with prevalent red and red-brownish plaques and hyper- and depigmentations similar to those of pityriasis versicolor. In all cases of this variety of EV malignancies occured invariably. In patients with EV, as also in--to a lesser extent--longstanding flat and/or common warts cell mediated immunity was in general lowered, but humoral specific anti-HPV antibodies were usually present. HPV type seems to be of a decisive significance for potential oncogenesis, because in a vast majority of cases EV due to HPV3 no malignancies occured in spite of anergy, whereas malignant transformation has been found in all cases due to HPV4, even in a patient with still preserved, although lowered, CMI.", "contents": "[New developments relating to papillomaviruses]. Molecular hybridization technique and immunofluorescence studies with use of specific immune sera against the purified virions isolated from various types of warts and wart-like lesions of epidermodysplasia verruciformis (EV) made it possible to detect four different types of human papilloma viruses (HPV). The recognition of the viruses is important because of the different morphology of the lesions induced and their various oncogenic potentials. HPV1 is mainly responsible for plantar warts, HPV2 for common (hand) warts, HPV3 has been found both in flat warts and in the variety of EV in which skin lesions are of flat wart type, the course is relatively more benign, and usually malignant transformation is not to be expected. HPV4 was up to now found exclusively in the cases of EV with prevalent red and red-brownish plaques and hyper- and depigmentations similar to those of pityriasis versicolor. In all cases of this variety of EV malignancies occured invariably. In patients with EV, as also in--to a lesser extent--longstanding flat and/or common warts cell mediated immunity was in general lowered, but humoral specific anti-HPV antibodies were usually present. HPV type seems to be of a decisive significance for potential oncogenesis, because in a vast majority of cases EV due to HPV3 no malignancies occured in spite of anergy, whereas malignant transformation has been found in all cases due to HPV4, even in a patient with still preserved, although lowered, CMI."}
{"id": "PMID:229089", "title": "Aetiology of breast cancer: a brief review.", "content": "Cancer of the human breast is probably a group of diseases which have different causes. Changes in hormonal status that increase breast cancer risk probably do so by 'promoting' tumour development rather than by 'initiating' it. Exogenous oestrogens seem to act as tumour promoters in this context, but there is to date no evidence that oral contraceptives, some of which contain oestrogens in low dosage, increase breast cancer risk. On the contrary, they appear to reduce the incidence of benign breast tumours. Prolactin-release is associated with increased mammary tumour incidence in rats but not in humans. There is no evidence that viruses or exposure to hair-dyes increase breast cancer risk. The fact that slight dietary restriction can dramatically reduce mammary tumour incidence in rats, suggests that dietary factors should be looked at more closely in the search for aetiological factors in man.", "contents": "Aetiology of breast cancer: a brief review. Cancer of the human breast is probably a group of diseases which have different causes. Changes in hormonal status that increase breast cancer risk probably do so by 'promoting' tumour development rather than by 'initiating' it. Exogenous oestrogens seem to act as tumour promoters in this context, but there is to date no evidence that oral contraceptives, some of which contain oestrogens in low dosage, increase breast cancer risk. On the contrary, they appear to reduce the incidence of benign breast tumours. Prolactin-release is associated with increased mammary tumour incidence in rats but not in humans. There is no evidence that viruses or exposure to hair-dyes increase breast cancer risk. The fact that slight dietary restriction can dramatically reduce mammary tumour incidence in rats, suggests that dietary factors should be looked at more closely in the search for aetiological factors in man."}
{"id": "PMID:229093", "title": "Oxygen-induced alteration of ventilation-perfusion relationships in rats.", "content": "The effect of oxygen breathing on shunt and ventilation-perfusion ratios (VA/Q) in anesthetized rats was studied using a modification of the multiple inert gas elimination technique. Base-line analyses showed hypoxemia in some animals breathing room air (arterial O2 tensions 48-70 Torr) associated with intrapulmonary shunts ranging from 0 to 22%, and variable low VA/Q lung regions as determined by calculation of the inert gas arterial-alveolar difference curve. Of nine rats that breathed 100% oxygen for 30 min, three showed increases in shunt (0% leads to 19%, 1.5% leads to 16%, 11% leads to 40%). These three animals had larger preexisting low VA/Q regions than the six that developed no shunt (0.48 +/- 0.15 vs. 0.17 +/- 0.03 (mean +/- SD); P less than 0.05). These data are compatible with the theory of absorption atelectasis. This study documents the usefulness of the inert gas elimination technique for studying  pulmonary gas exchange problems in small animals.", "contents": "Oxygen-induced alteration of ventilation-perfusion relationships in rats. The effect of oxygen breathing on shunt and ventilation-perfusion ratios (VA/Q) in anesthetized rats was studied using a modification of the multiple inert gas elimination technique. Base-line analyses showed hypoxemia in some animals breathing room air (arterial O2 tensions 48-70 Torr) associated with intrapulmonary shunts ranging from 0 to 22%, and variable low VA/Q lung regions as determined by calculation of the inert gas arterial-alveolar difference curve. Of nine rats that breathed 100% oxygen for 30 min, three showed increases in shunt (0% leads to 19%, 1.5% leads to 16%, 11% leads to 40%). These three animals had larger preexisting low VA/Q regions than the six that developed no shunt (0.48 +/- 0.15 vs. 0.17 +/- 0.03 (mean +/- SD); P less than 0.05). These data are compatible with the theory of absorption atelectasis. This study documents the usefulness of the inert gas elimination technique for studying  pulmonary gas exchange problems in small animals."}
{"id": "PMID:229094", "title": "FIP antibody test--interpretation and recommendations.", "content": "It is my opinion that the feline infectious peritonitis (FIP) antibody test currently is being over-used and over-interpreted. The test is of value to the practitioner in specific circumstances, but by itself it is not diagnostic of clinical FIP. Further, it is my opinion that clinically healthy FIP antibody-positive cats should not be euthanatized under a routine test and eradication policy.", "contents": "FIP antibody test--interpretation and recommendations. It is my opinion that the feline infectious peritonitis (FIP) antibody test currently is being over-used and over-interpreted. The test is of value to the practitioner in specific circumstances, but by itself it is not diagnostic of clinical FIP. Further, it is my opinion that clinically healthy FIP antibody-positive cats should not be euthanatized under a routine test and eradication policy."}
{"id": "PMID:229095", "title": "Anemia associated with feline leukemia virus infection.", "content": "One hundred feline leukemia virus-positive cats with evidence of anemia were examined to determine characteristics of the anemia. The anemia was usually normochromic and normocytic, with low reticulocyte counts but with normal white blood cell and platelet counts. About one third of the cats had splenomegaly. The bone marrow was usually hypocellular or normally cellular, with an increased myeloid to erythroid ratio. A history of recent stress or infection in many cases indicated that the immunosuppressive effect of feline leukemia virus may have been involved. Supportive treatment with periodic blood transfusions was successful in prolonging survival. Corticosteroids and androgens may have been beneficial in some cases.", "contents": "Anemia associated with feline leukemia virus infection. One hundred feline leukemia virus-positive cats with evidence of anemia were examined to determine characteristics of the anemia. The anemia was usually normochromic and normocytic, with low reticulocyte counts but with normal white blood cell and platelet counts. About one third of the cats had splenomegaly. The bone marrow was usually hypocellular or normally cellular, with an increased myeloid to erythroid ratio. A history of recent stress or infection in many cases indicated that the immunosuppressive effect of feline leukemia virus may have been involved. Supportive treatment with periodic blood transfusions was successful in prolonging survival. Corticosteroids and androgens may have been beneficial in some cases."}
{"id": "PMID:229099", "title": "Synthesis of DNA in the liver and testes of cadmium-tested partially hepatectomized rats.", "content": "Cadmium affects the induction of thymidine and thymidylate kinases in regenerating rat liver. EDTA administered simultaneously with cadmium reverses its inhibitory action on enzyme synthesis, and prevents the depression of thymidine incorporation into DNA observed in cadmium-treated animals. Zinc does not abolish the inhibitory action of cadmium on the synthesis of DNA in regenerating liver, and the incorporation of thymidine into DNA in the testes was inhibited more by intraperitoneal injection of cadmium plus zinc than by injection of cadmium alone. Inhibition of thymidine incorporation into DNA in the liver and testes was proportional to the amount of cadmium administered up to about 2 mg CdCl2/kg body weight, but surprisingly, higher doses of cadmium caused less inhibition.", "contents": "Synthesis of DNA in the liver and testes of cadmium-tested partially hepatectomized rats. Cadmium affects the induction of thymidine and thymidylate kinases in regenerating rat liver. EDTA administered simultaneously with cadmium reverses its inhibitory action on enzyme synthesis, and prevents the depression of thymidine incorporation into DNA observed in cadmium-treated animals. Zinc does not abolish the inhibitory action of cadmium on the synthesis of DNA in regenerating liver, and the incorporation of thymidine into DNA in the testes was inhibited more by intraperitoneal injection of cadmium plus zinc than by injection of cadmium alone. Inhibition of thymidine incorporation into DNA in the liver and testes was proportional to the amount of cadmium administered up to about 2 mg CdCl2/kg body weight, but surprisingly, higher doses of cadmium caused less inhibition."}
{"id": "PMID:229100", "title": "The use of Haemophilus gallinarum DNA-relaxing enzyme to investigate the relationship between the number of superhelical turns and the molecular weight in a negatively twisted DNA.", "content": "Covalently closed-circular, superhelical DNAs, including viral DNAs, bacterial plasmid DNAs, and bacteriophage replicative-form DNA, were treated with a small amount of Haemophilus gallinarum DNA-relaxing enzyme to generate incompletely relaxed DNA molecules. Each sample consisted of a set of closed-circular DNA molecules differing by one turn in their number of superhelical turns. The DNA samples were analyzed by agarose gel electrophoresis under conditions such that the electrophoretic mobility was a function of the number of turns. The numbers of superhelical turns (at 37 degrees C in 20 mM Tris-HCl (pH 7.5)-5 mM MgCl2) in the DNAs of pSC101 (5.8 megadaltons), Colicin E1 (4.2 megadaltons), pMR4 (4.0 megadaltons; recombinant between pBR322 and lambda DNA fragment), phi X174 replicative-form (RF) I, Simian virus 40 (SV40), and polyoma virus (3.4--3.6 megadaltons each), and lambda dv021 (2.05 megadaltons) were estimated to be 36, 27, 23--24, 20--21, 20--21, 20--21, and 11--13, respectively. It appears that the number of superhelical turns is mainly a function of the molecular weight of the DNA, at least in the substrates tested here.", "contents": "The use of Haemophilus gallinarum DNA-relaxing enzyme to investigate the relationship between the number of superhelical turns and the molecular weight in a negatively twisted DNA. Covalently closed-circular, superhelical DNAs, including viral DNAs, bacterial plasmid DNAs, and bacteriophage replicative-form DNA, were treated with a small amount of Haemophilus gallinarum DNA-relaxing enzyme to generate incompletely relaxed DNA molecules. Each sample consisted of a set of closed-circular DNA molecules differing by one turn in their number of superhelical turns. The DNA samples were analyzed by agarose gel electrophoresis under conditions such that the electrophoretic mobility was a function of the number of turns. The numbers of superhelical turns (at 37 degrees C in 20 mM Tris-HCl (pH 7.5)-5 mM MgCl2) in the DNAs of pSC101 (5.8 megadaltons), Colicin E1 (4.2 megadaltons), pMR4 (4.0 megadaltons; recombinant between pBR322 and lambda DNA fragment), phi X174 replicative-form (RF) I, Simian virus 40 (SV40), and polyoma virus (3.4--3.6 megadaltons each), and lambda dv021 (2.05 megadaltons) were estimated to be 36, 27, 23--24, 20--21, 20--21, 20--21, and 11--13, respectively. It appears that the number of superhelical turns is mainly a function of the molecular weight of the DNA, at least in the substrates tested here."}
{"id": "PMID:229101", "title": "Change in the fructose 1,6-bisphosphatase activity in sea urchin eggs following fertilization.", "content": "The activity of fructose 1,6-bisphosphatase [EC 3.1.3.11] in sea urchin eggs decreased following fertilization. During the first 30 min after fertilization, the activity was considerably lower than that in unfertilized eggs, but by 30 min the activity was similar to that in unfertilized eggs. The enzyme activity in fertilized eggs, estimated in the presence of EGTA, was similar to that in unfertilized eggs. The activity in unfertilized eggs was reduced by Ca2+ at concentrations between 1 X 10(-5) M and 5 X 10(-3) M. Immediately after fertilization, the enzyme was insensitive to concentrations of Ca2+ lower than 2 X 10(-4) M, but the Ca2+ sensitivity of the enzyme recovered 30 min after fertilization. In the presence of Ca2+ at concentrations higher than 2 X 10(-4) M, the enzyme activity in unfertilized eggs was similar to that in fertilized eggs. Mg2+ restored the Ca2+-induced inhibition of fructose 1,6-bisphosphatase. 3-Phosphoglycerate and citrate hardly affected the enzyme activity, and AMP at concentrations above 10 mM inhibited it.", "contents": "Change in the fructose 1,6-bisphosphatase activity in sea urchin eggs following fertilization. The activity of fructose 1,6-bisphosphatase [EC 3.1.3.11] in sea urchin eggs decreased following fertilization. During the first 30 min after fertilization, the activity was considerably lower than that in unfertilized eggs, but by 30 min the activity was similar to that in unfertilized eggs. The enzyme activity in fertilized eggs, estimated in the presence of EGTA, was similar to that in unfertilized eggs. The activity in unfertilized eggs was reduced by Ca2+ at concentrations between 1 X 10(-5) M and 5 X 10(-3) M. Immediately after fertilization, the enzyme was insensitive to concentrations of Ca2+ lower than 2 X 10(-4) M, but the Ca2+ sensitivity of the enzyme recovered 30 min after fertilization. In the presence of Ca2+ at concentrations higher than 2 X 10(-4) M, the enzyme activity in unfertilized eggs was similar to that in fertilized eggs. Mg2+ restored the Ca2+-induced inhibition of fructose 1,6-bisphosphatase. 3-Phosphoglycerate and citrate hardly affected the enzyme activity, and AMP at concentrations above 10 mM inhibited it."}
{"id": "PMID:229102", "title": "Transfer of cholestane spin label between lipid bilayer membranes and its molecular motion in membranes.", "content": "The relation between the molecular motion of a steroid in lipid membranes and the transfer rate between membranes was examined using radioactive cholestane spin label. Order parameters of the molecule were determined in bilayers composedof dipalmitoylglycerophosphocholine or egg yolk phosphatidylcholine at various temperatures. The line widths of the ESR signal of the cholestane spin label in membranes, which depend upon the rate of molecular axial rotation in the membranes, were also measured. The temperature dependences of these two parameters and of the transfer rate suggest a close correlation between the rate of molecular axial rotation and the transfer rate.", "contents": "Transfer of cholestane spin label between lipid bilayer membranes and its molecular motion in membranes. The relation between the molecular motion of a steroid in lipid membranes and the transfer rate between membranes was examined using radioactive cholestane spin label. Order parameters of the molecule were determined in bilayers composedof dipalmitoylglycerophosphocholine or egg yolk phosphatidylcholine at various temperatures. The line widths of the ESR signal of the cholestane spin label in membranes, which depend upon the rate of molecular axial rotation in the membranes, were also measured. The temperature dependences of these two parameters and of the transfer rate suggest a close correlation between the rate of molecular axial rotation and the transfer rate."}
{"id": "PMID:229103", "title": "Subunits of cytochrome a-type terminal oxidases derived from Thiobacillus novellus and Nitrobacter agilis.", "content": "Cytochrome a-type terminal oxidases derived from Thiobacillus novellus and Nitrobacter agilis have been purified to a homogeneous state as judged from their electrophoretic behavior and their subunit structures studied by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The T. novellus enzyme is composed of two kinds of subunits of 32,000 and 23,000 daltons and its minimum molecular weight is 55,000 on the basis of heme content and amino acid composition. The N. agilis enzyme also has two kinds of subunits of 40,000 and 27,000 daltons and its minimum molecular weight is 66,000 on the basis of heme content and amino acid composition. Therefore, the molecule of each enzyme is composed of two kinds of subunits which resemble the subunits of the eukaryotic cytochrome oxidase biosynthesized in the mitochondrion at least with respect to molecular weight.", "contents": "Subunits of cytochrome a-type terminal oxidases derived from Thiobacillus novellus and Nitrobacter agilis. Cytochrome a-type terminal oxidases derived from Thiobacillus novellus and Nitrobacter agilis have been purified to a homogeneous state as judged from their electrophoretic behavior and their subunit structures studied by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The T. novellus enzyme is composed of two kinds of subunits of 32,000 and 23,000 daltons and its minimum molecular weight is 55,000 on the basis of heme content and amino acid composition. The N. agilis enzyme also has two kinds of subunits of 40,000 and 27,000 daltons and its minimum molecular weight is 66,000 on the basis of heme content and amino acid composition. Therefore, the molecule of each enzyme is composed of two kinds of subunits which resemble the subunits of the eukaryotic cytochrome oxidase biosynthesized in the mitochondrion at least with respect to molecular weight."}
{"id": "PMID:229105", "title": "Induction of new-bone formation in the host bed by human bone-tumor transplants in athymic nude mice.", "content": "Specimens of twelve osteosarcomas, five chondrosarcomas, one giant-cell tumor, and five extraskeletal soft-tissue sarcomas were transplanted into male athymic nude (nu/nu) mice. Survival of the transplant was determined by the volume-doubling time and the sex chromatin of the tumor cells obtained from two female patients. By these criteria and the similarity of the histological composition of the original tumor and the transplant, survival occurred in four of twelve osteosarcomas and four of five chondrosarcomas. Without any local infiltration of lymphocytes or plasma cells, or other evidence of cell-mediated immunity, the surviving tumors regressed by the fourth week after the operation. Transformed osteoblasts and osteoprogenitor cells were replaced by fibrous connective tissue or fibrogenic tumor-tissue cells. Osteocytes degenerated and disappeared from the lacunae. The one giant-cell tumor transplant survived, growing very slowly, but by the end of the first week after transplantation whorls of mononucleated cells appeared in sites previously occupied by multinucleated cells. Transplants of leiomyosarcoma, liposarcoma, and synovioma (one tumor of each) degenerated. One of two fibrosarcomas survived transplantation. The most striking reaction of the mouse host bed was to encompass six of twelve osteosarcomas and four of five chondrosarcomas in deposits of normal living cartilage, bone, and bone marrow. The incidence of new bone inducedy by living transplants was only slightly greater than by implants of freeze-dried killed osteosarcoma tissue. Not one of five extraskeletal sarcomas, living or dead, induced bone formation. These observations suggest that an osteoinductive agent is transmitted by some osteosarcomas and chondrosarcomas. This agent initiates differentiation of host mesenchymal cells into normal non-tumorous cartilage and bone, which later colonized by bone marrow. Our observations present experimental evidence of the origin of the envelope of normal non-tumorous bone that may surround tumorous bone. In 1926, Phemister recognized the clinical significane of this envelope as a pitfall in the differential diagnosis of malignant bone tumors, chondrosarcoma, myositis ossificans circumscripta, and other neoplasms. He emphasized the importance of examining the entire specimen for the distribution of deposits of tumorous and normal bone. The induction of normal bone formation in the host bed surrounding transplants of osteosarcomas and some chondrosarcomas (but not transplants of fibrosarcoma, liposarcoma, or leiomyosarcoma) is evidence of a specific tumor-cell characteristic. Thus, the bone inductive response is not an unspecific reaction to injury from expansion or of tumor growth but a biological response to tumor-cell products. Transplants of human malignant tumors growing in the thymus-deficient mouse can be treated by combinations of radiation, amputation, and new chemotherapeutic agents...", "contents": "Induction of new-bone formation in the host bed by human bone-tumor transplants in athymic nude mice. Specimens of twelve osteosarcomas, five chondrosarcomas, one giant-cell tumor, and five extraskeletal soft-tissue sarcomas were transplanted into male athymic nude (nu/nu) mice. Survival of the transplant was determined by the volume-doubling time and the sex chromatin of the tumor cells obtained from two female patients. By these criteria and the similarity of the histological composition of the original tumor and the transplant, survival occurred in four of twelve osteosarcomas and four of five chondrosarcomas. Without any local infiltration of lymphocytes or plasma cells, or other evidence of cell-mediated immunity, the surviving tumors regressed by the fourth week after the operation. Transformed osteoblasts and osteoprogenitor cells were replaced by fibrous connective tissue or fibrogenic tumor-tissue cells. Osteocytes degenerated and disappeared from the lacunae. The one giant-cell tumor transplant survived, growing very slowly, but by the end of the first week after transplantation whorls of mononucleated cells appeared in sites previously occupied by multinucleated cells. Transplants of leiomyosarcoma, liposarcoma, and synovioma (one tumor of each) degenerated. One of two fibrosarcomas survived transplantation. The most striking reaction of the mouse host bed was to encompass six of twelve osteosarcomas and four of five chondrosarcomas in deposits of normal living cartilage, bone, and bone marrow. The incidence of new bone inducedy by living transplants was only slightly greater than by implants of freeze-dried killed osteosarcoma tissue. Not one of five extraskeletal sarcomas, living or dead, induced bone formation. These observations suggest that an osteoinductive agent is transmitted by some osteosarcomas and chondrosarcomas. This agent initiates differentiation of host mesenchymal cells into normal non-tumorous cartilage and bone, which later colonized by bone marrow. Our observations present experimental evidence of the origin of the envelope of normal non-tumorous bone that may surround tumorous bone. In 1926, Phemister recognized the clinical significane of this envelope as a pitfall in the differential diagnosis of malignant bone tumors, chondrosarcoma, myositis ossificans circumscripta, and other neoplasms. He emphasized the importance of examining the entire specimen for the distribution of deposits of tumorous and normal bone. The induction of normal bone formation in the host bed surrounding transplants of osteosarcomas and some chondrosarcomas (but not transplants of fibrosarcoma, liposarcoma, or leiomyosarcoma) is evidence of a specific tumor-cell characteristic. Thus, the bone inductive response is not an unspecific reaction to injury from expansion or of tumor growth but a biological response to tumor-cell products. Transplants of human malignant tumors growing in the thymus-deficient mouse can be treated by combinations of radiation, amputation, and new chemotherapeutic agents..."}
{"id": "PMID:229106", "title": "Fibrosarcoma of breast metastatic to stomach.", "content": "A case of fibrosarcoma of the breast metastatic to the stomach and small bowel is reported. Upper gastrointestinal bleeding secondary to a \"bull's eye\" or \"target\" gastric ulcer was successfully treated by surgical resection.", "contents": "Fibrosarcoma of breast metastatic to stomach. A case of fibrosarcoma of the breast metastatic to the stomach and small bowel is reported. Upper gastrointestinal bleeding secondary to a \"bull's eye\" or \"target\" gastric ulcer was successfully treated by surgical resection."}
{"id": "PMID:229107", "title": "Reversible accumulation of cholesteryl esters in macrophages incubated with acetylated lipoproteins.", "content": "Mouse peritoneal macrophages accumulate large amounts of cholesteryl ester when incubated with human low-density lipoprotein that has been modified by chemical acetylation (acetyl-LDL). This accumulation is related to a high-affinity cell surface binding site that mediates the uptake of acetyl-LDL by adsorptive endocytosis and its delivery to lysosomes. The current studies demonstrate that the cholesteryl ester accumulation can be considered in terms of a two-compartment model: (a) the incoming cholesteryl esters of acetyl-LDL are hydrolyzed in lysosomes, and (b) the resultant free cholesterol is re-esterified in the cytosol where the newly formed esters are stored as lipid droplets. The following biochemical and morphologic evidence supports the hydrolysis-re-esterification mechanism: (a) Incubation of macrophages with acetyl-LDL markedly increased the rate of cholesteryl ester synthesis from [14C]oleate, and this was accompanied by an increase in the acyl-CoA:cholesteryl acyltransferase activity of cell-free extracts. (b) When macrophages were incubated with reconstituted acetyl-LDL in which the endogenous cholesterol was replaced with [3H]-cholesteryl linoleate, the [3H]cholesteryl linoleate was hydrolyzed, and at least one-half of the resultant [3H]cholesterol was re-esterified to form [3H]cholesteryl oleate, which accumulated within the cell. The lysosomal enzyme inhibitor chloroquine inhibited the hydrolysis of the [3H]cholesteryl linoleate, thus preventing the formation of [3H]cholesteryl oleate and leading to the accumulation of unhydrolyzed [3H]cholesteryl linoleate within the cells. (c) In the electron microscope, macrophages incubated with acetyl-LDL had numerous cytoplasmic lipid droplets that were not surrounded by a limiting membrane. The time course of droplet accumulation was similar to the time course of cholesteryl ester accumulation as measured biochemically. (d) When acetyl-LDL was removed from the incubation medium, biochemical and morphological studies showed that cytoplasmic cholesteryl esters were rapidly hydrolyzed and that the resultant free cholesterol was excreted from the cell.", "contents": "Reversible accumulation of cholesteryl esters in macrophages incubated with acetylated lipoproteins. Mouse peritoneal macrophages accumulate large amounts of cholesteryl ester when incubated with human low-density lipoprotein that has been modified by chemical acetylation (acetyl-LDL). This accumulation is related to a high-affinity cell surface binding site that mediates the uptake of acetyl-LDL by adsorptive endocytosis and its delivery to lysosomes. The current studies demonstrate that the cholesteryl ester accumulation can be considered in terms of a two-compartment model: (a) the incoming cholesteryl esters of acetyl-LDL are hydrolyzed in lysosomes, and (b) the resultant free cholesterol is re-esterified in the cytosol where the newly formed esters are stored as lipid droplets. The following biochemical and morphologic evidence supports the hydrolysis-re-esterification mechanism: (a) Incubation of macrophages with acetyl-LDL markedly increased the rate of cholesteryl ester synthesis from [14C]oleate, and this was accompanied by an increase in the acyl-CoA:cholesteryl acyltransferase activity of cell-free extracts. (b) When macrophages were incubated with reconstituted acetyl-LDL in which the endogenous cholesterol was replaced with [3H]-cholesteryl linoleate, the [3H]cholesteryl linoleate was hydrolyzed, and at least one-half of the resultant [3H]cholesterol was re-esterified to form [3H]cholesteryl oleate, which accumulated within the cell. The lysosomal enzyme inhibitor chloroquine inhibited the hydrolysis of the [3H]cholesteryl linoleate, thus preventing the formation of [3H]cholesteryl oleate and leading to the accumulation of unhydrolyzed [3H]cholesteryl linoleate within the cells. (c) In the electron microscope, macrophages incubated with acetyl-LDL had numerous cytoplasmic lipid droplets that were not surrounded by a limiting membrane. The time course of droplet accumulation was similar to the time course of cholesteryl ester accumulation as measured biochemically. (d) When acetyl-LDL was removed from the incubation medium, biochemical and morphological studies showed that cytoplasmic cholesteryl esters were rapidly hydrolyzed and that the resultant free cholesterol was excreted from the cell."}
{"id": "PMID:229108", "title": "Isolation of human platelet plasma membranes with polylysine beads.", "content": "Human platelet plasma membranes were isolated with polylysine beads according to the technique developed by Jacobson and Branton (1977, Science [Wash. D. C.] 195:302--304). Lactoperoxidase-catalyzed surface iodination revealed that ninefold greater 125I specific activity was associated with the membranes isolated on beads than with whole platelets. Enrichment in the bead membrane preparation of the activities of membrane marker enzymes, bis(p-nitrophenyl)phosphate phosphodiesterase and Na,K-ATPase, was 8.0 and 4.4, respectively. Contamination with enzymes of other organelles, cytochrome oxidase and beta-glucuronidase, was relatively low as compared with membranes isolated by sucrose gradient centrifugation. Analysis by SDS polyacrylamide gel electrophoresis showed that a full complement of surface glycoproteins was present on the membranes isolated with polylysine beads. The polylysine bead technique is a rapid, reproducible and efficient method for the preparation of relatively pure platelet plasma membranes.", "contents": "Isolation of human platelet plasma membranes with polylysine beads. Human platelet plasma membranes were isolated with polylysine beads according to the technique developed by Jacobson and Branton (1977, Science [Wash. D. C.] 195:302--304). Lactoperoxidase-catalyzed surface iodination revealed that ninefold greater 125I specific activity was associated with the membranes isolated on beads than with whole platelets. Enrichment in the bead membrane preparation of the activities of membrane marker enzymes, bis(p-nitrophenyl)phosphate phosphodiesterase and Na,K-ATPase, was 8.0 and 4.4, respectively. Contamination with enzymes of other organelles, cytochrome oxidase and beta-glucuronidase, was relatively low as compared with membranes isolated by sucrose gradient centrifugation. Analysis by SDS polyacrylamide gel electrophoresis showed that a full complement of surface glycoproteins was present on the membranes isolated with polylysine beads. The polylysine bead technique is a rapid, reproducible and efficient method for the preparation of relatively pure platelet plasma membranes."}
{"id": "PMID:229109", "title": "Hormonally regulated phosphoprotein of turkey erythrocytes: localization to plasma membrane.", "content": "The catecholamine-stimulated cotransport of sodium and potassium ions across the plasma membrane of the turkey erythrocyte was previously found to be associated with increased 32P incorporation into a high molecular weight protein. To determine the subcellular localization of this phosphorylated protein, which we have termed goblin, a new method has been developed for isolation of pure plasma membranes from turkey erythrocytes. With this method, it has been demonstrated that goblin is located in the plasma membrane. Goblin is not extracted by solutions of low or high ionic strength but is partially extracted by nonionic detergents, indicating that it is not a component of turkey erythrocyte spectrin and suggesting that it may be an intrinsic protein of the plasma membrane. The data are compatible with a possible role for goblin in the hormonal control of ion movements across the plasma membrane.", "contents": "Hormonally regulated phosphoprotein of turkey erythrocytes: localization to plasma membrane. The catecholamine-stimulated cotransport of sodium and potassium ions across the plasma membrane of the turkey erythrocyte was previously found to be associated with increased 32P incorporation into a high molecular weight protein. To determine the subcellular localization of this phosphorylated protein, which we have termed goblin, a new method has been developed for isolation of pure plasma membranes from turkey erythrocytes. With this method, it has been demonstrated that goblin is located in the plasma membrane. Goblin is not extracted by solutions of low or high ionic strength but is partially extracted by nonionic detergents, indicating that it is not a component of turkey erythrocyte spectrin and suggesting that it may be an intrinsic protein of the plasma membrane. The data are compatible with a possible role for goblin in the hormonal control of ion movements across the plasma membrane."}
{"id": "PMID:229110", "title": "Elasmobranch rectal gland cell: autoradiographic localization of [3H]ouabain-sensitive Na, K-ATPase in rectal gland of dogfish, Squalus acanthias.", "content": "Specific binding of radiolabeled inhibitor was employed to localize the Na-pump sites (Na,K-ATPase) in rectal gland epithelium, a NaCl-secreting osmoregulatory tissue which is particularly rich in pump sites. Slices of gland tissue from spiny dogfish were incubated in suitable [3H]ouabain-containing media and then prepared for Na,K-ATPase assay, measurement of radiolabel binding, or quantitative freeze-dry autoradiography at the light microscope level. Gross freezing or drying artifacts were excluded by comparison with additional aldehyde-fixed slices. Characterization experiments demonstrated high-affinity binding which correlated with Na,K-ATPase inhibition and half-saturated at approximately 5 microM [3H]ouabain. At this concentration, the normal half-loading time was approximately 1 h and low-affinity binding to nonspecific sites was negligible. Autoradiographs from both 1- and 4-h incubated slices showed approximately 85% of the bound [3H]ouabain to be localized within a 1-micrometer wide boundary region where the highly infolded basal-lateral cell membrane are closest to the mitochondria. These results establish that most of the enormous Na,K-ATPase activity associated with rectal gland epithelium is in the basal-lateral cell membrane facing interstitial fluid and not in the luminal membrane facing secreted fluid. Moreover, distribution along the basal-lateral membrane appears to be nonuniform with a higher density of enzyme sites close to mitochondria.", "contents": "Elasmobranch rectal gland cell: autoradiographic localization of [3H]ouabain-sensitive Na, K-ATPase in rectal gland of dogfish, Squalus acanthias. Specific binding of radiolabeled inhibitor was employed to localize the Na-pump sites (Na,K-ATPase) in rectal gland epithelium, a NaCl-secreting osmoregulatory tissue which is particularly rich in pump sites. Slices of gland tissue from spiny dogfish were incubated in suitable [3H]ouabain-containing media and then prepared for Na,K-ATPase assay, measurement of radiolabel binding, or quantitative freeze-dry autoradiography at the light microscope level. Gross freezing or drying artifacts were excluded by comparison with additional aldehyde-fixed slices. Characterization experiments demonstrated high-affinity binding which correlated with Na,K-ATPase inhibition and half-saturated at approximately 5 microM [3H]ouabain. At this concentration, the normal half-loading time was approximately 1 h and low-affinity binding to nonspecific sites was negligible. Autoradiographs from both 1- and 4-h incubated slices showed approximately 85% of the bound [3H]ouabain to be localized within a 1-micrometer wide boundary region where the highly infolded basal-lateral cell membrane are closest to the mitochondria. These results establish that most of the enormous Na,K-ATPase activity associated with rectal gland epithelium is in the basal-lateral cell membrane facing interstitial fluid and not in the luminal membrane facing secreted fluid. Moreover, distribution along the basal-lateral membrane appears to be nonuniform with a higher density of enzyme sites close to mitochondria."}
{"id": "PMID:229111", "title": "Restriction of patching of bound concanavalin A after incorporation of arachidonic acid into the plasma membrane of virally transformed fibroblasts.", "content": "Topographical distribution of concanavalin A binding sites (CABS) was studied in two lines of virally transformed fibroblasts as a function of fatty acid composition. Fatty acid composition was manipulated by incubating cells in fatty acid, ATP, CoA, and delipidated fetal calf serum (FCS). VLM cells grown in medium containing 5% FCS have a clustered CABS distribution. Plasma membrane vesicles (PMVs) derived from these cells have an arachidonate content of 1.7%. Elevation of PMV arachidonate to 15.8% results in a marked restriction of CABS patching, while elevation to 6.8% is associated with intermediate restriction of patching. Restriction of patching is associated with increased microviscosity. CABS of Rous sarcoma virus-transformed chicken embryo fibroblasts (RSV-CEF) are also responsive to arachidonate enrichment medium. Whereas untreated cells have a clustered CABS distribution, cells incubated for 24 h in arachidonate enrichment medium have predominantly a dispersed CABS distribution. In both VLM cells and RSV-CEF, ATP, CoA, and delipidated FCS alone have no effect upon CABS mobility. Inhibition of CABS patching is also observed when aspirin is included in the arachidonate enrichment medium but not when the cells are incubated in prostaglandins, thus suggesting that the restriction of CABS mobility is not mediated by prostaglandins. Other fatty acids (palmitate, oleate, nonadecanoate) failed to restrict CABS movement. The inhibition of CABS mobility is independent of cell shape change.", "contents": "Restriction of patching of bound concanavalin A after incorporation of arachidonic acid into the plasma membrane of virally transformed fibroblasts. Topographical distribution of concanavalin A binding sites (CABS) was studied in two lines of virally transformed fibroblasts as a function of fatty acid composition. Fatty acid composition was manipulated by incubating cells in fatty acid, ATP, CoA, and delipidated fetal calf serum (FCS). VLM cells grown in medium containing 5% FCS have a clustered CABS distribution. Plasma membrane vesicles (PMVs) derived from these cells have an arachidonate content of 1.7%. Elevation of PMV arachidonate to 15.8% results in a marked restriction of CABS patching, while elevation to 6.8% is associated with intermediate restriction of patching. Restriction of patching is associated with increased microviscosity. CABS of Rous sarcoma virus-transformed chicken embryo fibroblasts (RSV-CEF) are also responsive to arachidonate enrichment medium. Whereas untreated cells have a clustered CABS distribution, cells incubated for 24 h in arachidonate enrichment medium have predominantly a dispersed CABS distribution. In both VLM cells and RSV-CEF, ATP, CoA, and delipidated FCS alone have no effect upon CABS mobility. Inhibition of CABS patching is also observed when aspirin is included in the arachidonate enrichment medium but not when the cells are incubated in prostaglandins, thus suggesting that the restriction of CABS mobility is not mediated by prostaglandins. Other fatty acids (palmitate, oleate, nonadecanoate) failed to restrict CABS movement. The inhibition of CABS mobility is independent of cell shape change."}
{"id": "PMID:229112", "title": "Cell cycle dependence of transformation expression in mouse cells transformed by a thermosensitive mutant (Ts-121) of polyoma virus.", "content": "Change in division capability as a phenotypic expression of cellular transformation was investigated by using one of the temperature-sensitive (ts) mutants of the polyoma virus-transformed cell line, the 121-6-5 cells of BALB/3T3. When contact -inhibited cells were treated with hyaluronidase at 39 degrees C, a single round of cell division was induced after which cell growth was inhibited by cell density. However, if the cells were incubated at 35 degrees C, after the enzyme treatment, density-inhibition block disappeared and the cells entered a second division. This indicates that the release of cells from density-inhibition depends on the low temperature incubation. The ability of cells to complete a second division was examined by shifting the cells from 39 degrees C to 35 degrees C during different phases of the first division cycle after the enzyme-treatment. A 6-hour incubation of S phase cells at 35 degrees C resulted in a second cycle of division, while the 24-hour incubation of G1 cells at 35 degrees C did not induce a second round of division. These results suggest that expression of the transformed phenotype in 121-6-5 cells is clearly dependent upon both the temperature and the phase of the division cycle.", "contents": "Cell cycle dependence of transformation expression in mouse cells transformed by a thermosensitive mutant (Ts-121) of polyoma virus. Change in division capability as a phenotypic expression of cellular transformation was investigated by using one of the temperature-sensitive (ts) mutants of the polyoma virus-transformed cell line, the 121-6-5 cells of BALB/3T3. When contact -inhibited cells were treated with hyaluronidase at 39 degrees C, a single round of cell division was induced after which cell growth was inhibited by cell density. However, if the cells were incubated at 35 degrees C, after the enzyme treatment, density-inhibition block disappeared and the cells entered a second division. This indicates that the release of cells from density-inhibition depends on the low temperature incubation. The ability of cells to complete a second division was examined by shifting the cells from 39 degrees C to 35 degrees C during different phases of the first division cycle after the enzyme-treatment. A 6-hour incubation of S phase cells at 35 degrees C resulted in a second cycle of division, while the 24-hour incubation of G1 cells at 35 degrees C did not induce a second round of division. These results suggest that expression of the transformed phenotype in 121-6-5 cells is clearly dependent upon both the temperature and the phase of the division cycle."}
{"id": "PMID:229113", "title": "Hemicyst formation stimulated by cyclic AMP in dog kidney cell line MDCK.", "content": "Certain epithelial cell lines have morphologic, physiologic, biochemical and pharmacologic characteristics of transporting epithelia from intact organs. In this paper we show that dibutyryl cyclic AMP, 5' AMP, adenosine and cyclic AMP phosphodiesterase inhibitors stimulate hemicyst formation by the dog kidney cell line MDCK. It is suggested that this effect is explained by elevation of intracellular cyclic AMP levels by means of an exogenous non-metabolizable source of cyclic AMP, phosphodiesterase inhibition or adenyl cyclase stimulation. Since hemicyst formation is in part due to transepithelial fluid transport, these findings raise the possibility that this fraction might be modulated by cAMP in an established cell line. We believe that cultured epithelial cells may provide an exploitable model system to investigate at the cellular and subcellular levels, the mechanism by which cyclic AMP modifies water and solute movements across epithelia.", "contents": "Hemicyst formation stimulated by cyclic AMP in dog kidney cell line MDCK. Certain epithelial cell lines have morphologic, physiologic, biochemical and pharmacologic characteristics of transporting epithelia from intact organs. In this paper we show that dibutyryl cyclic AMP, 5' AMP, adenosine and cyclic AMP phosphodiesterase inhibitors stimulate hemicyst formation by the dog kidney cell line MDCK. It is suggested that this effect is explained by elevation of intracellular cyclic AMP levels by means of an exogenous non-metabolizable source of cyclic AMP, phosphodiesterase inhibition or adenyl cyclase stimulation. Since hemicyst formation is in part due to transepithelial fluid transport, these findings raise the possibility that this fraction might be modulated by cAMP in an established cell line. We believe that cultured epithelial cells may provide an exploitable model system to investigate at the cellular and subcellular levels, the mechanism by which cyclic AMP modifies water and solute movements across epithelia."}
{"id": "PMID:229114", "title": "Regulation of the proliferative response in Rous sarcoma virus transformed chicken embryo fibroblasts by serum and multiplication-stimulating activity (MSA).", "content": "A temperature sensitive mutant of Rous sarcoma virus (tsNY68) was used to obtain cultures of quiescent virus-infected chicken embryo fibroblasts arrested by serum starvation at the non-permissive temperature. Upon shift to the permissive temperature, these cells enter the replicative cell cycle as evidenced by increases in 2-deoxyglucose uptake, 3H-thymidine incorporation and percent labeled nuclei. These changes occur in the absence of serum and the cells become morphologically transformed within eight to ten hours after the temperature shift. Entry into the S phase temporally resembles that of normal quiescent fibroblasts stimulated with serum. This experimental system was used to examine the proliferative response of transformed cells to serum and purified multiplication-stimulating activity (MSA) during the transition from the resting to the growing state. Data are presented which show that the presence of serum in the medium enhances the proliferative response of quiescent infected cells shifted to the permissive temperature over those shifted in the absence of serum. In contrast, the presence of MSA has no additional effect on the response exhibited by infected cells shifted to the permissive temperature in serum-free medium. Labeled MSA binding experiments show that this lack of response is not due to a loss of MSA receptors on the cell surface since transformed cells are still capable of binding MSA at the same level as normal cells. The results are consistent with the hypothesis that the set of biochemical events initiated by MSA in normal cells are turned on in infected cells shifted to the permissive temperature by the activation of the src gene product.", "contents": "Regulation of the proliferative response in Rous sarcoma virus transformed chicken embryo fibroblasts by serum and multiplication-stimulating activity (MSA). A temperature sensitive mutant of Rous sarcoma virus (tsNY68) was used to obtain cultures of quiescent virus-infected chicken embryo fibroblasts arrested by serum starvation at the non-permissive temperature. Upon shift to the permissive temperature, these cells enter the replicative cell cycle as evidenced by increases in 2-deoxyglucose uptake, 3H-thymidine incorporation and percent labeled nuclei. These changes occur in the absence of serum and the cells become morphologically transformed within eight to ten hours after the temperature shift. Entry into the S phase temporally resembles that of normal quiescent fibroblasts stimulated with serum. This experimental system was used to examine the proliferative response of transformed cells to serum and purified multiplication-stimulating activity (MSA) during the transition from the resting to the growing state. Data are presented which show that the presence of serum in the medium enhances the proliferative response of quiescent infected cells shifted to the permissive temperature over those shifted in the absence of serum. In contrast, the presence of MSA has no additional effect on the response exhibited by infected cells shifted to the permissive temperature in serum-free medium. Labeled MSA binding experiments show that this lack of response is not due to a loss of MSA receptors on the cell surface since transformed cells are still capable of binding MSA at the same level as normal cells. The results are consistent with the hypothesis that the set of biochemical events initiated by MSA in normal cells are turned on in infected cells shifted to the permissive temperature by the activation of the src gene product."}
{"id": "PMID:229115", "title": "Selective high metabolic lability of uridine, guanosine and cytosine triphosphates in response to glucose deprivation and refeeding of untransformed and polyoma virus-transformed hamster fibroblasts.", "content": "Sugar deprivation of hamster fibroblasts (NIL) affected the steady state levels (pool sizes) of cellular acid soluble nucleotides in the folloing fashion: the pools of UTP, GTP and CTP decreased to a much greater extent than the cellular ATP pools, with the UTP pools undergoing the most dramatic reduction. Sugar deprivation of polyoma-transformed NIL cells (PyNIL) yielded even sharper decreases in the nucleoside triphosphate pools with relative changes similar to those of the untransformed cells. Inhibition of protein synthesis by cycloheximide, initiated at the onset of (and continued during) sugar deprivation, prevented the reduction in pool sizes and yielded values slightly higher than those observed for pool sizes in cells cultured in sugar-supplemented medium. Refeeding glucose to sugar-depleted hamster fibroblasts led to rapid increases (within 1 hour) in the UTP and CTP pools to levels well above the pool sizes observed in cells which were continuously cultured (16 hours) in sugar supplemented medium. Feeding NIL or PyNIL cells with fructose instead of glucose as the only hexose source did not appreciably affect any of the ribonucleoside triphosphate pool sizes. Measurements of hexose uptake by NIL and PyNIL cells under a variety of conditions suggest that hexose transport is not regulated by the total cellular pools of ATP or any of the other ribonucleoside triphosphates.", "contents": "Selective high metabolic lability of uridine, guanosine and cytosine triphosphates in response to glucose deprivation and refeeding of untransformed and polyoma virus-transformed hamster fibroblasts. Sugar deprivation of hamster fibroblasts (NIL) affected the steady state levels (pool sizes) of cellular acid soluble nucleotides in the folloing fashion: the pools of UTP, GTP and CTP decreased to a much greater extent than the cellular ATP pools, with the UTP pools undergoing the most dramatic reduction. Sugar deprivation of polyoma-transformed NIL cells (PyNIL) yielded even sharper decreases in the nucleoside triphosphate pools with relative changes similar to those of the untransformed cells. Inhibition of protein synthesis by cycloheximide, initiated at the onset of (and continued during) sugar deprivation, prevented the reduction in pool sizes and yielded values slightly higher than those observed for pool sizes in cells cultured in sugar-supplemented medium. Refeeding glucose to sugar-depleted hamster fibroblasts led to rapid increases (within 1 hour) in the UTP and CTP pools to levels well above the pool sizes observed in cells which were continuously cultured (16 hours) in sugar supplemented medium. Feeding NIL or PyNIL cells with fructose instead of glucose as the only hexose source did not appreciably affect any of the ribonucleoside triphosphate pool sizes. Measurements of hexose uptake by NIL and PyNIL cells under a variety of conditions suggest that hexose transport is not regulated by the total cellular pools of ATP or any of the other ribonucleoside triphosphates."}
{"id": "PMID:229118", "title": "Substantial rise of plasma beta-endorphin levels after insulin-induced hypoglycemia in human subjects.", "content": "To elucidate whether insulin-induced hypoglycemia enhances the release of beta-endorphin in man, plasma extracts obtained from healthy subjects and patients with Graves' disease before and 45 min after insulin injection were subjected to gel chromatography, and the fractions obtained were measured by RIA for beta-endorphin. In four healthy subjects, basal plasma beta-endorphin levels were less than 3 to 3.1 pg/ml, and the levels rose substantially to 47.5 +/- 12.4 pg/ml (mean +/- SE) 45 min after insulin injection. Basal plasma beta-endorphin levels in three hyperthyroid patinets (less than 3 to 3.8 pg/ml) did not seem to be different from those in healthy subjects; however, the rise after insulin injection tended to be higher in cases of hyperthyroidism, with a peak value of 68.5 +/- 9.7 pg/ml. Plasma beta-lipotropin and ACTH levels also rose in parallel with beta-endorphin in response to insulin-induced hypoglycemia in both healthy subjects and hyperthyroid patients. It would thus appear that beta-endorphin, like ACTH or beta-lipotropin, is released in human subjects by hypoglycemic stress.", "contents": "Substantial rise of plasma beta-endorphin levels after insulin-induced hypoglycemia in human subjects. To elucidate whether insulin-induced hypoglycemia enhances the release of beta-endorphin in man, plasma extracts obtained from healthy subjects and patients with Graves' disease before and 45 min after insulin injection were subjected to gel chromatography, and the fractions obtained were measured by RIA for beta-endorphin. In four healthy subjects, basal plasma beta-endorphin levels were less than 3 to 3.1 pg/ml, and the levels rose substantially to 47.5 +/- 12.4 pg/ml (mean +/- SE) 45 min after insulin injection. Basal plasma beta-endorphin levels in three hyperthyroid patinets (less than 3 to 3.8 pg/ml) did not seem to be different from those in healthy subjects; however, the rise after insulin injection tended to be higher in cases of hyperthyroidism, with a peak value of 68.5 +/- 9.7 pg/ml. Plasma beta-lipotropin and ACTH levels also rose in parallel with beta-endorphin in response to insulin-induced hypoglycemia in both healthy subjects and hyperthyroid patients. It would thus appear that beta-endorphin, like ACTH or beta-lipotropin, is released in human subjects by hypoglycemic stress."}
{"id": "PMID:229121", "title": "Entamoeba histolytica: efficacy of microscopic, cultural, and serological techniques for laboratory diagnosis.", "content": "Of 110 subjects with clinical evidence of amebiasis, 15 (14%) were shown to be infected with Entamoeba histolytica. Microscopic examination of stool specimens rendered a diagnosis in all eight cases of localized intestinal infection, but in only one of seven patients with invasive amebiasis. Culture was concomitantly diagnostic in six patients intestinal amebiasis and in one patient with extraintestinal infection. Assay for antibody to E. histolytica by counterimmunoelectrophoresis and indirect hemagglutination were each 100% effective in all cases of invasive amebiasis and in diagnosing two of eight patients with intestinal infection. Stool specimens of 15 patients revealing intestinal parasites other than E. histolytica failed to demonstrate cultural or serological evidence of amebiasis. Low levels of antibody were observed in the indirect hemagglutination assay in four patients with disease other than amebiasis and in three control sera positive for rheumatoid factor. By counterimmunoelectrophoresis, reactive sera were only encountered among those derived from patients with amebiasis. Six of seven patients with hepatic amebiasis may have gone undiagnosed if not for serology.", "contents": "Entamoeba histolytica: efficacy of microscopic, cultural, and serological techniques for laboratory diagnosis. Of 110 subjects with clinical evidence of amebiasis, 15 (14%) were shown to be infected with Entamoeba histolytica. Microscopic examination of stool specimens rendered a diagnosis in all eight cases of localized intestinal infection, but in only one of seven patients with invasive amebiasis. Culture was concomitantly diagnostic in six patients intestinal amebiasis and in one patient with extraintestinal infection. Assay for antibody to E. histolytica by counterimmunoelectrophoresis and indirect hemagglutination were each 100% effective in all cases of invasive amebiasis and in diagnosing two of eight patients with intestinal infection. Stool specimens of 15 patients revealing intestinal parasites other than E. histolytica failed to demonstrate cultural or serological evidence of amebiasis. Low levels of antibody were observed in the indirect hemagglutination assay in four patients with disease other than amebiasis and in three control sera positive for rheumatoid factor. By counterimmunoelectrophoresis, reactive sera were only encountered among those derived from patients with amebiasis. Six of seven patients with hepatic amebiasis may have gone undiagnosed if not for serology."}
{"id": "PMID:229122", "title": "Factors involved in enzyme-linked immunoassay of viruses and evaluation of the method for identification of enteroviruses.", "content": "A quantitative enzyme-linked immunosorbent assay was used for identification of selected enteroviruses: poliovirus type 1, echovirus type 6, coxsackievirus A type 9, and coxsackievirus B types 1 through 6. Partially purified viral antigens or virus-specific antibodies were adsorbed to polystyrene spectrophotometer cuvettes, which permitted the assays to be reported and compared in terms of enzyme units specifically reacting. Both the adsorbed antigen and the adsorbed antibody methods were approximately equal in terms of sensitivity and specificity of reaction. By use [14C]leucine-labeled enteroviruses, the amount of virus that bound to the plastics used was shown to be dependent on the purity of the virus preparation used, but it was higher than the amount that was bound by plastics coated with viral antibody. Diluents which contained 0.15% (vol/vol) Tween 20 and 2.0% (wt/vol) bovine serum albumin in phosphate-buffered saline, pH 7.2, were found to be the most effective in inhibiting nonspecific adsorption of immunoreagents. However, the presence of these inhibitors in phosphate-buffered  saline solutions also caused desorption of virus or viral antibody during immunoassays; the amount of virus desorption varied with the type of preparation used, and antibody desorption was dependent on the concentration of antibody initially used for adsorption. For specific identification of a given enterovirus type by the enzyme-linked immunosorbent assay method used, approximately 10(5) plaque-forming units of virus per assay tube were required.", "contents": "Factors involved in enzyme-linked immunoassay of viruses and evaluation of the method for identification of enteroviruses. A quantitative enzyme-linked immunosorbent assay was used for identification of selected enteroviruses: poliovirus type 1, echovirus type 6, coxsackievirus A type 9, and coxsackievirus B types 1 through 6. Partially purified viral antigens or virus-specific antibodies were adsorbed to polystyrene spectrophotometer cuvettes, which permitted the assays to be reported and compared in terms of enzyme units specifically reacting. Both the adsorbed antigen and the adsorbed antibody methods were approximately equal in terms of sensitivity and specificity of reaction. By use [14C]leucine-labeled enteroviruses, the amount of virus that bound to the plastics used was shown to be dependent on the purity of the virus preparation used, but it was higher than the amount that was bound by plastics coated with viral antibody. Diluents which contained 0.15% (vol/vol) Tween 20 and 2.0% (wt/vol) bovine serum albumin in phosphate-buffered saline, pH 7.2, were found to be the most effective in inhibiting nonspecific adsorption of immunoreagents. However, the presence of these inhibitors in phosphate-buffered  saline solutions also caused desorption of virus or viral antibody during immunoassays; the amount of virus desorption varied with the type of preparation used, and antibody desorption was dependent on the concentration of antibody initially used for adsorption. For specific identification of a given enterovirus type by the enzyme-linked immunosorbent assay method used, approximately 10(5) plaque-forming units of virus per assay tube were required."}
{"id": "PMID:229123", "title": "Counterimmunoelectroosmophoresis for detection of neonatal calf diarrhea coronavirus: methodology and comparison with electron microscopy.", "content": "A counterimmunoelectroosmophoresis (CIE) technique is described for the detection of calf diarrhea coronavirus antigens in intestinal contents. The antibody reagent was prepared in rabbits against the Nebraska calf diarrhea coronavirus adapted to Vero cells and purified by density gradient centrifugation. The method was applied to intestinal contents of diarrheic and normal calves and compared with electron microscopy (EM). Calf coronavirus antigens were detected in intestinal contents of 44% (21/48) of the diarrheic calves and 24% (4/17) of the normal calves. Two precipitin lines could be observed in the majority of the positive samples. When compared with EM, CIE detected more positive animals. In only two cases (2/20) CIE was negative despite the visualization of coronavirus particles by EM.", "contents": "Counterimmunoelectroosmophoresis for detection of neonatal calf diarrhea coronavirus: methodology and comparison with electron microscopy. A counterimmunoelectroosmophoresis (CIE) technique is described for the detection of calf diarrhea coronavirus antigens in intestinal contents. The antibody reagent was prepared in rabbits against the Nebraska calf diarrhea coronavirus adapted to Vero cells and purified by density gradient centrifugation. The method was applied to intestinal contents of diarrheic and normal calves and compared with electron microscopy (EM). Calf coronavirus antigens were detected in intestinal contents of 44% (21/48) of the diarrheic calves and 24% (4/17) of the normal calves. Two precipitin lines could be observed in the majority of the positive samples. When compared with EM, CIE detected more positive animals. In only two cases (2/20) CIE was negative despite the visualization of coronavirus particles by EM."}
{"id": "PMID:229124", "title": "Cytological diagnosis of virus-infected cells in Papanicolaou smears and its application in clinical practice.", "content": "The cytopathic changes of herpes simplex virus, varicella-zoster virus, the human polyomaviruses, and the trachoma agent can be recognised in smears prepared from a wide variety of specimens. The morphology of virus-infected cells is described, and the clinical value of these observations is discussed. Cytological diagnosis offers a rapid and convenient method of detecting infection with these viruses which can be confirmed by conventional virological method while the patient is still in the acute stages of the disease. Confirmation can also be made retrospectively by reprocessing cells, identified in the Papanicolaou smear, for electron microscopy. Screening for virus-infected cells in cytological smears is a technique that can be developed in any pathology laboratory prepared to provide a comprehensive cytology service, and it is proving to be a useful tool in clinical diagnosis and applied research.", "contents": "Cytological diagnosis of virus-infected cells in Papanicolaou smears and its application in clinical practice. The cytopathic changes of herpes simplex virus, varicella-zoster virus, the human polyomaviruses, and the trachoma agent can be recognised in smears prepared from a wide variety of specimens. The morphology of virus-infected cells is described, and the clinical value of these observations is discussed. Cytological diagnosis offers a rapid and convenient method of detecting infection with these viruses which can be confirmed by conventional virological method while the patient is still in the acute stages of the disease. Confirmation can also be made retrospectively by reprocessing cells, identified in the Papanicolaou smear, for electron microscopy. Screening for virus-infected cells in cytological smears is a technique that can be developed in any pathology laboratory prepared to provide a comprehensive cytology service, and it is proving to be a useful tool in clinical diagnosis and applied research."}
{"id": "PMID:229125", "title": "Carcinoma in situ of the male breast.", "content": "Two cases of carcinoma in situ of the male breast are described: in one patient it arose as a complication of gynecomastia; in the other, it occurred 'de novo' and proceeded to infiltration with widespread metastases. We reviewed 233 cases diagnosed clinically and histopathologically as gynecomastia to see if we could discover other instances of malignant transformation but none was found. Thirty-two cases of infiltrating male breast cancer were also examined. In 11 there was associated intraduct change. In only one of the 32 cases was there evidence of associated microscopic gynecomastia.", "contents": "Carcinoma in situ of the male breast. Two cases of carcinoma in situ of the male breast are described: in one patient it arose as a complication of gynecomastia; in the other, it occurred 'de novo' and proceeded to infiltration with widespread metastases. We reviewed 233 cases diagnosed clinically and histopathologically as gynecomastia to see if we could discover other instances of malignant transformation but none was found. Thirty-two cases of infiltrating male breast cancer were also examined. In 11 there was associated intraduct change. In only one of the 32 cases was there evidence of associated microscopic gynecomastia."}
{"id": "PMID:229128", "title": "Winter vomiting disease caused by calicivirus.", "content": "The clinical, epidemiological, and virological features of an outbreak of winter vomiting disease among London schoolchildren are described. Evidence is presented to support the view that this epidemic was caused by a human calicivirus, a virus not previously shown to be associated with this disease in man.", "contents": "Winter vomiting disease caused by calicivirus. The clinical, epidemiological, and virological features of an outbreak of winter vomiting disease among London schoolchildren are described. Evidence is presented to support the view that this epidemic was caused by a human calicivirus, a virus not previously shown to be associated with this disease in man."}
{"id": "PMID:229130", "title": "An immunohistochemical study of distribution of carcinoembryonic antigen in epithelial tumours of the ovary.", "content": "An immunohistochemical study of the tissue CEA content of 82 epithelial neoplasms of the ovary has shown that mucinous tumours contain more of this substance than do their serous counterparts; otherwise a knowledge of tissue CEA content appears to be of little value in the differential histological diagnosis of this group of neoplasms. Among mucinous tumours there is only a partial correspondence between their degree of malignancy, as assessed histologically, and their content of CEA. It is postulated that immunohistological study of tissue CEA may add a degree of finesse to morphological analysis of these neoplasms and thus allow for a more precise grading of their degree of malignancy.", "contents": "An immunohistochemical study of distribution of carcinoembryonic antigen in epithelial tumours of the ovary. An immunohistochemical study of the tissue CEA content of 82 epithelial neoplasms of the ovary has shown that mucinous tumours contain more of this substance than do their serous counterparts; otherwise a knowledge of tissue CEA content appears to be of little value in the differential histological diagnosis of this group of neoplasms. Among mucinous tumours there is only a partial correspondence between their degree of malignancy, as assessed histologically, and their content of CEA. It is postulated that immunohistological study of tissue CEA may add a degree of finesse to morphological analysis of these neoplasms and thus allow for a more precise grading of their degree of malignancy."}
{"id": "PMID:229133", "title": "Factors involved in skin carcinogenesis.", "content": "A personal account of skin carcinogenesis is given based on forty years of investigation of normal and pathologic anatomy of the human skin. Symbiosis of acral portions of adnexa and of melanocytes with epidermal keratinocytes is stressed, and perversion of symbiosis to parasitism in tumor formation is discussed. The role of the basement membrane as a combined effort of, and filter between, ectoderm and mesoderm is stressed, and the nature of basal cell epithelioma as the least differentiated member of the tribe of fibroepithelial adnexal tumors is outlined. Experimental data supporting the promoting role of specific mesodermal stroma in basalioma formation and maintenance are presented.", "contents": "Factors involved in skin carcinogenesis. A personal account of skin carcinogenesis is given based on forty years of investigation of normal and pathologic anatomy of the human skin. Symbiosis of acral portions of adnexa and of melanocytes with epidermal keratinocytes is stressed, and perversion of symbiosis to parasitism in tumor formation is discussed. The role of the basement membrane as a combined effort of, and filter between, ectoderm and mesoderm is stressed, and the nature of basal cell epithelioma as the least differentiated member of the tribe of fibroepithelial adnexal tumors is outlined. Experimental data supporting the promoting role of specific mesodermal stroma in basalioma formation and maintenance are presented."}
{"id": "PMID:229134", "title": "Immunology of human warts.", "content": "Rapid advances have occurred in the characterization of human papilloma virus (HPV) types applying the new advanced techniques of restriction endonuclease analysis and molecular hybridization to human wart virus. Human papilloma virus can no longer be viewed as a single, homogeneous virus producing all varieties of clinical warts. At least three antigenically heterogeneous HPV types have been associated with common and plantar warts. Two additional HPV types have been found in patients with epidermodysplasia verruciformis. Condylomata acuminata and laryngeal papillomas contain viruses which are also distinct from the preceding viruses and may represent additional HPV types. This antigenic heterogeneity of HPV has important implications concerning the immunology of human warts which have not been taken into account in most previously published studies. Both antibody and cell-mediated responses may be seen in patients with active warts, but many patients with warts have no demonstrable immune reactions. The role of immunity in wart regression remains poorly understood. Nevertheless, the increased frequency of warts in patients receiving immunosuppressive drugs and with immune deficiency states and the immunologic alterations which occur in patients with regressing or cured warts compared to patients with active warts, particularly the increased frequency of cell-mediated responses and antibodies specific for viral antigens, support a possible role for immunity in the resolution of warts. The evidence to date, however, does not prove that immune mechanisms are directly responsible for the elimination of warts.", "contents": "Immunology of human warts. Rapid advances have occurred in the characterization of human papilloma virus (HPV) types applying the new advanced techniques of restriction endonuclease analysis and molecular hybridization to human wart virus. Human papilloma virus can no longer be viewed as a single, homogeneous virus producing all varieties of clinical warts. At least three antigenically heterogeneous HPV types have been associated with common and plantar warts. Two additional HPV types have been found in patients with epidermodysplasia verruciformis. Condylomata acuminata and laryngeal papillomas contain viruses which are also distinct from the preceding viruses and may represent additional HPV types. This antigenic heterogeneity of HPV has important implications concerning the immunology of human warts which have not been taken into account in most previously published studies. Both antibody and cell-mediated responses may be seen in patients with active warts, but many patients with warts have no demonstrable immune reactions. The role of immunity in wart regression remains poorly understood. Nevertheless, the increased frequency of warts in patients receiving immunosuppressive drugs and with immune deficiency states and the immunologic alterations which occur in patients with regressing or cured warts compared to patients with active warts, particularly the increased frequency of cell-mediated responses and antibodies specific for viral antigens, support a possible role for immunity in the resolution of warts. The evidence to date, however, does not prove that immune mechanisms are directly responsible for the elimination of warts."}
{"id": "PMID:229135", "title": "Tortuous vertebrobasilar arteries causing cranial nerve syndromes: screening by computed tomography.", "content": "Considerable concern with cranial nerve syndromes has often required detailed information of the relationship between the vertebrobasilar system and the brainstem. The obvious invasiveness of conventional vertebral angiography poses the question of whether computed tomography (CT) might serve as a satisfactory technique or even as a sufficient diagnostic method. During a 12 month period, 12 of 250 patients with cranial nerve syndromes were diagnosed by CT as having vertebrobasilar ectasia. This communication correlates the clinical symptomatology with angiography and CT and presents evidence that CT alone can prove satisfactory.", "contents": "Tortuous vertebrobasilar arteries causing cranial nerve syndromes: screening by computed tomography. Considerable concern with cranial nerve syndromes has often required detailed information of the relationship between the vertebrobasilar system and the brainstem. The obvious invasiveness of conventional vertebral angiography poses the question of whether computed tomography (CT) might serve as a satisfactory technique or even as a sufficient diagnostic method. During a 12 month period, 12 of 250 patients with cranial nerve syndromes were diagnosed by CT as having vertebrobasilar ectasia. This communication correlates the clinical symptomatology with angiography and CT and presents evidence that CT alone can prove satisfactory."}
{"id": "PMID:229136", "title": "Tumors of the glomus jugulare complex (chemodectomas) demonstrated by cranial computed tomography.", "content": "The appearance of six glomus tumors (four glomus jugulotympanicum and two vagal body tumors) is demonstrated in four patients. In one case, glomus tumor tissue is visualized by computed tomography (CT) inside the tympanic cavity. The importance of the use of different window settings is stressed. The value of CT in comparison to arteriography and polytomography is briefly discussed. Computed tomography is recommended in the evaluation of the course of a glomus tumor and in radiation therapy treatment planning of these tumors.", "contents": "Tumors of the glomus jugulare complex (chemodectomas) demonstrated by cranial computed tomography. The appearance of six glomus tumors (four glomus jugulotympanicum and two vagal body tumors) is demonstrated in four patients. In one case, glomus tumor tissue is visualized by computed tomography (CT) inside the tympanic cavity. The importance of the use of different window settings is stressed. The value of CT in comparison to arteriography and polytomography is briefly discussed. Computed tomography is recommended in the evaluation of the course of a glomus tumor and in radiation therapy treatment planning of these tumors."}
{"id": "PMID:229137", "title": "Determination of mycophenolic acid, penicillic acid, patulin, sterigmatocystin, and aflatoxins in cheese.", "content": "A method has been developed for detection of aflatoxins, mycophenolic acid, patulin, penicillic acid, and sterigmatocystin in cheese. It is based on selective extraction with a mixture of equal volumes of 5% sodium chloride, methanol, and aceton, precipitation of caseins at -25 C, defatting with hexane, and removal of extraneous matter by transfer of mycotoxins to chloroform and ethyl acetate. The extract is purified further by column chromatography. Mycotoxins are quantitated on thin layer chromatograms by fluorescence comparisons. Mycophenolic acid, patulin, and penicillic acid are visualized with diethylamine. The limits of detection in cheese are about 20 micrograms/kg for mycophenolic acid, patulin, and sterigmatocystin, 30 microgram/kg for pencillic acid, and 1 microgram/kg for aflatoxins B1 and M1.", "contents": "Determination of mycophenolic acid, penicillic acid, patulin, sterigmatocystin, and aflatoxins in cheese. A method has been developed for detection of aflatoxins, mycophenolic acid, patulin, penicillic acid, and sterigmatocystin in cheese. It is based on selective extraction with a mixture of equal volumes of 5% sodium chloride, methanol, and aceton, precipitation of caseins at -25 C, defatting with hexane, and removal of extraneous matter by transfer of mycotoxins to chloroform and ethyl acetate. The extract is purified further by column chromatography. Mycotoxins are quantitated on thin layer chromatograms by fluorescence comparisons. Mycophenolic acid, patulin, and penicillic acid are visualized with diethylamine. The limits of detection in cheese are about 20 micrograms/kg for mycophenolic acid, patulin, and sterigmatocystin, 30 microgram/kg for pencillic acid, and 1 microgram/kg for aflatoxins B1 and M1."}
{"id": "PMID:229138", "title": "Enzyme immunoassay for measuring lipoprotein lipase activator in milk.", "content": "A method for determining the relative amount of lipoprotein lipase activator in milk was developed. The activator was measured in arbitrary units which were based on a standard curve for high density lipoprotein. Activator varied between cows not only in whole milk but also in skim milk and milk serum. Most of the activator was in the skim milk, and the amount of activator in milk serum varied between 32 and 91% of that in skim milk. In seven of eight cows, free fatty acids of milk increased with increasing units of activator.", "contents": "Enzyme immunoassay for measuring lipoprotein lipase activator in milk. A method for determining the relative amount of lipoprotein lipase activator in milk was developed. The activator was measured in arbitrary units which were based on a standard curve for high density lipoprotein. Activator varied between cows not only in whole milk but also in skim milk and milk serum. Most of the activator was in the skim milk, and the amount of activator in milk serum varied between 32 and 91% of that in skim milk. In seven of eight cows, free fatty acids of milk increased with increasing units of activator."}
{"id": "PMID:229139", "title": "The effect of epinephrine on pulpal microcirculation.", "content": "The effect of epinephrine (Epi) on the microcirculation of the pulp and its neuropharmacological mechanism has been established, as well as the existence of alpha adrenergic receptors in the blood vessels of the pulp. In addition, our results showed that local injections of Epi at doses greater than 10(-8) M produced an extreme drop in intrapulpal pressure (IPP). This effect was not obtained when Epi was injected intravenously.", "contents": "The effect of epinephrine on pulpal microcirculation. The effect of epinephrine (Epi) on the microcirculation of the pulp and its neuropharmacological mechanism has been established, as well as the existence of alpha adrenergic receptors in the blood vessels of the pulp. In addition, our results showed that local injections of Epi at doses greater than 10(-8) M produced an extreme drop in intrapulpal pressure (IPP). This effect was not obtained when Epi was injected intravenously."}
{"id": "PMID:229140", "title": "Collagenolytic activity of crevicular fluid  and of adjacent gingival tissue.", "content": "The fluid in and gingival tissue lining periodontal pockets were collected from male patients undergoing periodontal therapy. The collagenolytic activity of the crevicular fluid, and the ability of the gingiva in culture to degrade (a) an exogenous collagen substrate, and (b) endogenous collagen newly synthesized and labeled with H3-hydroxyproline, were related to the severity of gingival inflammation. Although inflammation appeared to have only a slight effect on gingival collagenolytic activity and on the turnover of collagen newly synthesized in culture, a marked effect was observed on the collagenase activity in the crevicular fluid. This study suggests that the collagen destructive activity of the periodontal lesion can be assessed by monitoring crevicular fluid collagenolytic activity.", "contents": "Collagenolytic activity of crevicular fluid  and of adjacent gingival tissue. The fluid in and gingival tissue lining periodontal pockets were collected from male patients undergoing periodontal therapy. The collagenolytic activity of the crevicular fluid, and the ability of the gingiva in culture to degrade (a) an exogenous collagen substrate, and (b) endogenous collagen newly synthesized and labeled with H3-hydroxyproline, were related to the severity of gingival inflammation. Although inflammation appeared to have only a slight effect on gingival collagenolytic activity and on the turnover of collagen newly synthesized in culture, a marked effect was observed on the collagenase activity in the crevicular fluid. This study suggests that the collagen destructive activity of the periodontal lesion can be assessed by monitoring crevicular fluid collagenolytic activity."}
{"id": "PMID:229146", "title": "Insomnia in the elderly: treatment with flurazepam hydrochloride.", "content": "Under sleep-laboratory control, the efficacy of flurazepam hydrochloride (15 mg) was evaluated in 6 women (age range, 67-82 years) with objectively verified insomnia. A 15-night, single-blind, crossover procedure was followed. Sleep records obtained during 3 placebo-baseline nights, 7 consecutive flurazepam nights, and 3 placebo-withdrawal nights were evaluated by means of electroencephalographic, electro-oculographic, and electromyographic criteria. A statistically significant reduction in sleep latency and total awake time and a corresponding increase in total sleep time (P less than 0.05) were demonstrated during the active drug period. No evidence of diminishing effectiveness was observed during the 7 days of drug administration. For the rapid-eye-movement (REM) stage, a significant decrease (P less than 0.05) in mean REM percent was noted during the drug period despite an increase in mean absolute REM time. No REM rebound occurred upon drug withdrawal. There were no significant changes in mean percentages for stages 3 and 4 during the drug period and the withdrawal period. Adverse reactions were rare (chiefly some daytime drowsiness in 2 subjects).", "contents": "Insomnia in the elderly: treatment with flurazepam hydrochloride. Under sleep-laboratory control, the efficacy of flurazepam hydrochloride (15 mg) was evaluated in 6 women (age range, 67-82 years) with objectively verified insomnia. A 15-night, single-blind, crossover procedure was followed. Sleep records obtained during 3 placebo-baseline nights, 7 consecutive flurazepam nights, and 3 placebo-withdrawal nights were evaluated by means of electroencephalographic, electro-oculographic, and electromyographic criteria. A statistically significant reduction in sleep latency and total awake time and a corresponding increase in total sleep time (P less than 0.05) were demonstrated during the active drug period. No evidence of diminishing effectiveness was observed during the 7 days of drug administration. For the rapid-eye-movement (REM) stage, a significant decrease (P less than 0.05) in mean REM percent was noted during the drug period despite an increase in mean absolute REM time. No REM rebound occurred upon drug withdrawal. There were no significant changes in mean percentages for stages 3 and 4 during the drug period and the withdrawal period. Adverse reactions were rare (chiefly some daytime drowsiness in 2 subjects)."}
{"id": "PMID:229147", "title": "Prolactin receptors: a comparison between chloramine-T and lactoperoxidase iodination.", "content": "The binding properties of chloramine-T iodinated oPRL (using a modified iodination procedure) to prolactin receptors of female rat liver membrane particles were compared with those of lactoperoxidase iodinated oPRL. The results indicated that both iodination methods provided 125I-oPRLs which were suitable for receptor binding studies. Our results suggested that chloramine-T 125I-oPRL was even better than lactoperoxidase 125I-oPRL in terms of lower nonspecific binding. The chloramine-T iodinated oPRL was used to study the prolactin receptors in rat ovaries and DMBA induced rat mammary tumors. The results showed that the amount of prolactin receptors in rat ovaries was related to the plasma level of prolactin as it had been reported in liver by other investigators. The study of prolactin receptors in rat mammary tumors indicated that the prolactin receptor content of hormone dependent mammary tumors was much higher than that of hormone independent mammary tumors.", "contents": "Prolactin receptors: a comparison between chloramine-T and lactoperoxidase iodination. The binding properties of chloramine-T iodinated oPRL (using a modified iodination procedure) to prolactin receptors of female rat liver membrane particles were compared with those of lactoperoxidase iodinated oPRL. The results indicated that both iodination methods provided 125I-oPRLs which were suitable for receptor binding studies. Our results suggested that chloramine-T 125I-oPRL was even better than lactoperoxidase 125I-oPRL in terms of lower nonspecific binding. The chloramine-T iodinated oPRL was used to study the prolactin receptors in rat ovaries and DMBA induced rat mammary tumors. The results showed that the amount of prolactin receptors in rat ovaries was related to the plasma level of prolactin as it had been reported in liver by other investigators. The study of prolactin receptors in rat mammary tumors indicated that the prolactin receptor content of hormone dependent mammary tumors was much higher than that of hormone independent mammary tumors."}
{"id": "PMID:229148", "title": "Serum somatomedin and insulin levels in tumor hypoglycemia.", "content": "Serum concentrations of somatomedin and immunoreactive insulin were measured during the hypoglycemic phase of 3 patients with tumor hypoglycemia. Normal amounts of somatomedin were detected in their fasting sera, but they may have been inappropriate (or associated with enhanced insulin-like activity) considering the degree of hypoglycemia. Fasting serum insulin levels were consistently depressed, and in two of the cases remained low even after an oral glucose load. Nevertheless, the blood glucose concentrations of these two patients fell to hypoglycemic levels again by 3 hours; the mechanism of this reactive hypoglycemia remains unclear.", "contents": "Serum somatomedin and insulin levels in tumor hypoglycemia. Serum concentrations of somatomedin and immunoreactive insulin were measured during the hypoglycemic phase of 3 patients with tumor hypoglycemia. Normal amounts of somatomedin were detected in their fasting sera, but they may have been inappropriate (or associated with enhanced insulin-like activity) considering the degree of hypoglycemia. Fasting serum insulin levels were consistently depressed, and in two of the cases remained low even after an oral glucose load. Nevertheless, the blood glucose concentrations of these two patients fell to hypoglycemic levels again by 3 hours; the mechanism of this reactive hypoglycemia remains unclear."}
{"id": "PMID:229150", "title": "Thyrotropin receptor-adenylate cyclase system in plasma membranes from normal and diseased human thyroid glands.", "content": "Thyrotropin binding characteristics and adenylate cyclase (AC) activity of thyroid plasma membranes were studied in 52 tissues from normal and diseased human thyroids. Data from normal glands, Graves' goiters, non toxic multinodular goiters and nodular and perinodular tissue of toxic nodular goiters show the same basal, TSH- and NaF- stimulated adenylate cyclase activities (no. = 45; 34.1 +/- 3.2 (m +/- SE), 378 +/- 43, 298 +/- 48 pmol cAMP x min-1 x mg membrane protein-1), the same stimulability of AC by TSH (11.3 +/- 1.4--fold over basal level) and by NaF (8.1 +/- 1.8-fold), the same apparent TSH binding equilibrium constants (5.6 +/- 0.7 and 406 +/- 57 nM) and the same TSH binding site concentrations (2.2 +/- 0.4, 27.8 +/- 5.9 pmol x mg membrane protein-1). Alterations of the TSH receptor and of the AC were detected in membranes from tumoral and metastatic lymph node tissues from thyroid papillary carcinoma and in the thyroid tissue from post-radioiodide therapy thyroiditis. These observations suggest that: (i) hyperthyroidism in Graves' disease or toxic nodular goiter does not result in and is not a consequence of an alteration in the TSH receptor-adenylate cyclase system; (ii) there is no evidence supporting a relationship between the studied membrane properties and clinical or histological status; (iii) membrane abnormalities detected in thyroid carcinoma vary widely; (iv) studies of these membrane alterations might be of interest in the therapeutic management of thyroid carcinoma and may lead to a better understanding of the receptor-adenylate system.", "contents": "Thyrotropin receptor-adenylate cyclase system in plasma membranes from normal and diseased human thyroid glands. Thyrotropin binding characteristics and adenylate cyclase (AC) activity of thyroid plasma membranes were studied in 52 tissues from normal and diseased human thyroids. Data from normal glands, Graves' goiters, non toxic multinodular goiters and nodular and perinodular tissue of toxic nodular goiters show the same basal, TSH- and NaF- stimulated adenylate cyclase activities (no. = 45; 34.1 +/- 3.2 (m +/- SE), 378 +/- 43, 298 +/- 48 pmol cAMP x min-1 x mg membrane protein-1), the same stimulability of AC by TSH (11.3 +/- 1.4--fold over basal level) and by NaF (8.1 +/- 1.8-fold), the same apparent TSH binding equilibrium constants (5.6 +/- 0.7 and 406 +/- 57 nM) and the same TSH binding site concentrations (2.2 +/- 0.4, 27.8 +/- 5.9 pmol x mg membrane protein-1). Alterations of the TSH receptor and of the AC were detected in membranes from tumoral and metastatic lymph node tissues from thyroid papillary carcinoma and in the thyroid tissue from post-radioiodide therapy thyroiditis. These observations suggest that: (i) hyperthyroidism in Graves' disease or toxic nodular goiter does not result in and is not a consequence of an alteration in the TSH receptor-adenylate cyclase system; (ii) there is no evidence supporting a relationship between the studied membrane properties and clinical or histological status; (iii) membrane abnormalities detected in thyroid carcinoma vary widely; (iv) studies of these membrane alterations might be of interest in the therapeutic management of thyroid carcinoma and may lead to a better understanding of the receptor-adenylate system."}
{"id": "PMID:229151", "title": "The adenylate cyclase-cyclic AMP-phosphodiesterase system in pathological human thyroid.", "content": "The adenylate cyclase-cyclic AMP-phosphodiesterase system of human thyroid tissues adjacent to cold nodules (control), two follicular adenomas, one hyperplastic thyroid and one hyperfunctioning follicular carcinoma have been compared. In the hyperfunctional follicular carcinoma the basal adenylate cyclase is much higher than in control tissue, carcinoma adenylate cyclase does not respond to TSH and prostaglandin E1, whereas it responds normally to fluoride. In the hyperplastic, but hypofunctional thyroid the basal adenylate cyclase is higher than in normal tissue whereas the response to TSH, PGE1, and fluoride is normal. No difference between the follicular adenomas and normal thyroid stimulated and unstimulated adenylate cyclase was observed. Furthermore in various thyroid tissues no changes in the level of cyclic AMP phosphodiesterase was found. Our data indicate a greater change in the synthesis rather than in degradation of cyclic AMP in the human pathological thyroids studied.", "contents": "The adenylate cyclase-cyclic AMP-phosphodiesterase system in pathological human thyroid. The adenylate cyclase-cyclic AMP-phosphodiesterase system of human thyroid tissues adjacent to cold nodules (control), two follicular adenomas, one hyperplastic thyroid and one hyperfunctioning follicular carcinoma have been compared. In the hyperfunctional follicular carcinoma the basal adenylate cyclase is much higher than in control tissue, carcinoma adenylate cyclase does not respond to TSH and prostaglandin E1, whereas it responds normally to fluoride. In the hyperplastic, but hypofunctional thyroid the basal adenylate cyclase is higher than in normal tissue whereas the response to TSH, PGE1, and fluoride is normal. No difference between the follicular adenomas and normal thyroid stimulated and unstimulated adenylate cyclase was observed. Furthermore in various thyroid tissues no changes in the level of cyclic AMP phosphodiesterase was found. Our data indicate a greater change in the synthesis rather than in degradation of cyclic AMP in the human pathological thyroids studied."}
{"id": "PMID:229152", "title": "Failure of oral bromocriptine to affect hypergastrinemia in two patients with the Zollinger-Ellison syndrome.", "content": "Bromocriptine was administered to 2 subjects with gastrin-secreting tumors of the pancreas. The absorption of the drug was confirmed by a rise in growth hormone levels but no change in the elevated serum gastrin levels were observed. Bromocriptine does not appear to affect gastrin hypersecretion in the way that it influences the hypersecretion of pituitary hormones.", "contents": "Failure of oral bromocriptine to affect hypergastrinemia in two patients with the Zollinger-Ellison syndrome. Bromocriptine was administered to 2 subjects with gastrin-secreting tumors of the pancreas. The absorption of the drug was confirmed by a rise in growth hormone levels but no change in the elevated serum gastrin levels were observed. Bromocriptine does not appear to affect gastrin hypersecretion in the way that it influences the hypersecretion of pituitary hormones."}
{"id": "PMID:229153", "title": "Lack of effect of bromocriptine on ACTH levels in patients with bilateral adrenalectomy for pituitary-dependent Cushing's syndrome.", "content": "Bromocriptine lowers plasma ACTH levels in patients with pituitary-dependent Cushing's syndrome. It seemed possible that the drug would also be effective in patients who had been adrenalectomised for the disease. The effect of 5.0 mg of bromocriptine on plasma ACTH and prolactin levels in 13 patients, bilaterally adrenalectomised for pituitary-dependent Cushing's syndrome, was therefore studied. In only one patient was a fall in plasma ACTH observed. This may be of doubtful significance since marked spontaneous fluctuation in plasma ACTH levels were found in the five patients tested. Bromocriptine lowered the plasma prolactin in all of the patients, including two with hyperprolactinaemia.", "contents": "Lack of effect of bromocriptine on ACTH levels in patients with bilateral adrenalectomy for pituitary-dependent Cushing's syndrome. Bromocriptine lowers plasma ACTH levels in patients with pituitary-dependent Cushing's syndrome. It seemed possible that the drug would also be effective in patients who had been adrenalectomised for the disease. The effect of 5.0 mg of bromocriptine on plasma ACTH and prolactin levels in 13 patients, bilaterally adrenalectomised for pituitary-dependent Cushing's syndrome, was therefore studied. In only one patient was a fall in plasma ACTH observed. This may be of doubtful significance since marked spontaneous fluctuation in plasma ACTH levels were found in the five patients tested. Bromocriptine lowered the plasma prolactin in all of the patients, including two with hyperprolactinaemia."}
{"id": "PMID:229155", "title": "Evaluation of the operative treatment of syndactyly.", "content": "A review of the records of 61 patients with 176 surgically treated webs was completed to evaluate the results of the different operative techniques used to separate the fingers. The postoperative follow-up period averaged 14 years, with a range from 2 to 38 years. The patients were assessed in two groups: those with major associated anomalies and those in whom syndactyly was the principal anomaly. Recurrence of the webs and flexion and extension contractures occurred more often when split-thickness grafts were used. To obtain a satisfactory result, a second procedure was necessary in 59% of patients with major associated anomalies, and in 30% of the patients who had syndactyly as the principal abnormality. Two types of patients were found to require subsequent operations: children treated prior to 18 months of age and those with complex syndactyly.", "contents": "Evaluation of the operative treatment of syndactyly. A review of the records of 61 patients with 176 surgically treated webs was completed to evaluate the results of the different operative techniques used to separate the fingers. The postoperative follow-up period averaged 14 years, with a range from 2 to 38 years. The patients were assessed in two groups: those with major associated anomalies and those in whom syndactyly was the principal anomaly. Recurrence of the webs and flexion and extension contractures occurred more often when split-thickness grafts were used. To obtain a satisfactory result, a second procedure was necessary in 59% of patients with major associated anomalies, and in 30% of the patients who had syndactyly as the principal abnormality. Two types of patients were found to require subsequent operations: children treated prior to 18 months of age and those with complex syndactyly."}
{"id": "PMID:229156", "title": "Autoradiographic visualization of beta-adrenergic receptors in normal and denervated skeletal muscle.", "content": "Autoradiographic localization of beta-adrenergic receptors in rat skeletal muscle in vivo was achieved utilizing [125I]-iodohydroxybenzylpindolol, a potent beta-adrenergic blocker with high affinity and specificity for those receptors. In normal muscle the beta-adrenergic receptors were localized mainly to blood vessels, arterioles greater than venules, with much less concentration of grains over the fascicles of muscle fibers. One week after denervation there was an increase in binding both to blood vessels and muscle fibers, more so in soleus and gactrocnemius than in extensor digitorum longus. While these results parallel in vitro biochemical studies, they dictate caution when inferring cellular localization of beta-adrenergic receptors (and other molecules) solely on the basis of biochemical techniques applied to subcellular fractions of whole-organ homogenates.", "contents": "Autoradiographic visualization of beta-adrenergic receptors in normal and denervated skeletal muscle. Autoradiographic localization of beta-adrenergic receptors in rat skeletal muscle in vivo was achieved utilizing [125I]-iodohydroxybenzylpindolol, a potent beta-adrenergic blocker with high affinity and specificity for those receptors. In normal muscle the beta-adrenergic receptors were localized mainly to blood vessels, arterioles greater than venules, with much less concentration of grains over the fascicles of muscle fibers. One week after denervation there was an increase in binding both to blood vessels and muscle fibers, more so in soleus and gactrocnemius than in extensor digitorum longus. While these results parallel in vitro biochemical studies, they dictate caution when inferring cellular localization of beta-adrenergic receptors (and other molecules) solely on the basis of biochemical techniques applied to subcellular fractions of whole-organ homogenates."}
{"id": "PMID:229157", "title": "Cytochemical bioassay and radioimmunoassay of ACTH in noise stressed rats.", "content": "Serum corticosterone and ACTH levels were measured in rats subjected to one and two 30 min intervals of noise (100 dB, 250--20,000 Hz). Both hormones were elevated immediately after noise exposure, dropped below pre-exposure levels after a 2 hr recovery interval and were again elevated with a second exposure. The ratio of immunoactive to bioactive ACTH was slightly depressed after one exposure and markedly depressed after two successive noise exposures (relative to controls) indicating that multiple exposure to auditory stimulation effects a proportionally greater output of bioactive ACTH.", "contents": "Cytochemical bioassay and radioimmunoassay of ACTH in noise stressed rats. Serum corticosterone and ACTH levels were measured in rats subjected to one and two 30 min intervals of noise (100 dB, 250--20,000 Hz). Both hormones were elevated immediately after noise exposure, dropped below pre-exposure levels after a 2 hr recovery interval and were again elevated with a second exposure. The ratio of immunoactive to bioactive ACTH was slightly depressed after one exposure and markedly depressed after two successive noise exposures (relative to controls) indicating that multiple exposure to auditory stimulation effects a proportionally greater output of bioactive ACTH."}
{"id": "PMID:229158", "title": "Pathology of the endocrine pancreas.", "content": "An immunocytochemical analysis of 94 pancreatic endocrine tumors revealed that 73 tumors were multicellular. Significant amounts of somatostatin and human pancreatic polypeptide were found by radioimmunoassay in extracts of 19 and 17 tumors resp., in addition to the hormone causing the clinical syndrome. Numerous tumors contained ductular structures. In the surrounding pancreatic parenchyma a proliferation of small ducts and budding-off from the ductular epithelium of endocrine cells was often observed. These features are hallmarks of nesidioblastosis of the endocrine pancreas which is a hyperplasia. In multiple endocrine neoplasia I hyperplasia of the endocrine pancreas is combined with larger nodules, currently labeled tumors. On the basis of these findings it is conceivable that pancreatic endocrine tumors are not primarily neoplastic and autonomous but that they are rather of hyperplastic origin.", "contents": "Pathology of the endocrine pancreas. An immunocytochemical analysis of 94 pancreatic endocrine tumors revealed that 73 tumors were multicellular. Significant amounts of somatostatin and human pancreatic polypeptide were found by radioimmunoassay in extracts of 19 and 17 tumors resp., in addition to the hormone causing the clinical syndrome. Numerous tumors contained ductular structures. In the surrounding pancreatic parenchyma a proliferation of small ducts and budding-off from the ductular epithelium of endocrine cells was often observed. These features are hallmarks of nesidioblastosis of the endocrine pancreas which is a hyperplasia. In multiple endocrine neoplasia I hyperplasia of the endocrine pancreas is combined with larger nodules, currently labeled tumors. On the basis of these findings it is conceivable that pancreatic endocrine tumors are not primarily neoplastic and autonomous but that they are rather of hyperplastic origin."}
{"id": "PMID:229160", "title": "Comparison of immunofluorescence and radioimmunoassay for detecting IgM antibody in infants with the congenital rubella syndrome.", "content": "Immunofluorescence (IF) and radioimmunoassay (RIA) have been compared as methods for detecting IgM antibody in 124 infants with confirmed or suspected congenital rubella. IF was used to test sucrose density gradient fractions and RIA to test fractions and whole serum. When fractions were tested IF and RIA were equally specific and distinguished clearly between IgM and IgG, but RIA was the more sensitive method. The RIA titre in whole serum was always greater than in the peak IgM fraction and there was no evidence that testing the serum, rather than the fraction, could result in failure to detect IgM. With some sera RIA gave low titres which became negative after absorption with IgG-coated latex beads. The mechanism of this 'false positive' effect, which may have been due to IgM with anti-IgG activity, was not investigated, but if it can be removed by absorption it need not reduce the specificity of the test. During the first 6 months of life IgM antibody was detected by RIA in 30 out of 32 unfractionated sera and by IF in fractions from 28 of these. After the age of 6 months IgM was found progressively less frequently and the greater sensitivity of RIA became a more obvious advantage: 17 out of 60 specimens were positive by RIA and 11 of these were negative by IF. RIA testing of whole serum appears to be an economical, specific and sensitive method for detecting IgM antibody in congenital rubella, of particular value when the titre of antibody is low.", "contents": "Comparison of immunofluorescence and radioimmunoassay for detecting IgM antibody in infants with the congenital rubella syndrome. Immunofluorescence (IF) and radioimmunoassay (RIA) have been compared as methods for detecting IgM antibody in 124 infants with confirmed or suspected congenital rubella. IF was used to test sucrose density gradient fractions and RIA to test fractions and whole serum. When fractions were tested IF and RIA were equally specific and distinguished clearly between IgM and IgG, but RIA was the more sensitive method. The RIA titre in whole serum was always greater than in the peak IgM fraction and there was no evidence that testing the serum, rather than the fraction, could result in failure to detect IgM. With some sera RIA gave low titres which became negative after absorption with IgG-coated latex beads. The mechanism of this 'false positive' effect, which may have been due to IgM with anti-IgG activity, was not investigated, but if it can be removed by absorption it need not reduce the specificity of the test. During the first 6 months of life IgM antibody was detected by RIA in 30 out of 32 unfractionated sera and by IF in fractions from 28 of these. After the age of 6 months IgM was found progressively less frequently and the greater sensitivity of RIA became a more obvious advantage: 17 out of 60 specimens were positive by RIA and 11 of these were negative by IF. RIA testing of whole serum appears to be an economical, specific and sensitive method for detecting IgM antibody in congenital rubella, of particular value when the titre of antibody is low."}
{"id": "PMID:229161", "title": "A blastogenic test for foot-and-mouth disease.", "content": "A blastogenic test to detect peripheral blood leukocytes specifically sensitized to foot-and-mouth disease virus antigen is described. The test is carried out in microtitre plates and optimum conditions were found by titration. These employed 7.5 x 10(5) cells/well and 20 complement fixing units of antigen. Peak [3H]thymidine incorporation was found to take place at 2-3 days.", "contents": "A blastogenic test for foot-and-mouth disease. A blastogenic test to detect peripheral blood leukocytes specifically sensitized to foot-and-mouth disease virus antigen is described. The test is carried out in microtitre plates and optimum conditions were found by titration. These employed 7.5 x 10(5) cells/well and 20 complement fixing units of antigen. Peak [3H]thymidine incorporation was found to take place at 2-3 days."}
{"id": "PMID:229162", "title": "Application of the enzyme linked immunosorbent assay to the detection and identification of foot-and-mouth disease viruses.", "content": "An indirect enzyme linked immunosorbent assay (ELISA) was applied to the detection and identification of foot-and-mouth disease (FMD) virus types. The test proved successful for the specific detection of virus from infected tissue culture, and from epithelial tissues from bovines suspected of having FMD. The ELISA compared favourably with the complement fixation (CF) test, being more sensitive and unaffected by anticomplementary factors.", "contents": "Application of the enzyme linked immunosorbent assay to the detection and identification of foot-and-mouth disease viruses. An indirect enzyme linked immunosorbent assay (ELISA) was applied to the detection and identification of foot-and-mouth disease (FMD) virus types. The test proved successful for the specific detection of virus from infected tissue culture, and from epithelial tissues from bovines suspected of having FMD. The ELISA compared favourably with the complement fixation (CF) test, being more sensitive and unaffected by anticomplementary factors."}
{"id": "PMID:229163", "title": "Incidence of bluetongue virus precipitating antibodies in sera of some domestic animals in the Sudan.", "content": "To determine the presence and prevalence of bluetongue (BT) infection in a variety of domestic animal species in different geographical regions of the Sudan, a serological study using the agar gel precipitation technique was initiated. A total of 2142 serum samples were examined. Of the numbers tested approximately 28% of sheep, 11.2% of goats, 8% of cattle and 4.9% of camels were positive for group-specific antibodies to BT virus antigen, indicating previous exposure to BT infection. None of the samples tested from horses or donkeys were positive. The findings suggest that the disease is widely distributed in most parts of the Sudan where possible insect vectors prevail and may be endemic in sheep in Juba District, Equatoria Province, Southern Region. Goats appeared to have some degree of resistance to infection compared with sheep, and there seemed to be no significant differences in positive rates between farm and free-range cattle. It is concluded that BT infection may cause clinical disease in sheep, while it is probably subclinical or inapparent in goats, cattle and camels of the Sudan.", "contents": "Incidence of bluetongue virus precipitating antibodies in sera of some domestic animals in the Sudan. To determine the presence and prevalence of bluetongue (BT) infection in a variety of domestic animal species in different geographical regions of the Sudan, a serological study using the agar gel precipitation technique was initiated. A total of 2142 serum samples were examined. Of the numbers tested approximately 28% of sheep, 11.2% of goats, 8% of cattle and 4.9% of camels were positive for group-specific antibodies to BT virus antigen, indicating previous exposure to BT infection. None of the samples tested from horses or donkeys were positive. The findings suggest that the disease is widely distributed in most parts of the Sudan where possible insect vectors prevail and may be endemic in sheep in Juba District, Equatoria Province, Southern Region. Goats appeared to have some degree of resistance to infection compared with sheep, and there seemed to be no significant differences in positive rates between farm and free-range cattle. It is concluded that BT infection may cause clinical disease in sheep, while it is probably subclinical or inapparent in goats, cattle and camels of the Sudan."}
{"id": "PMID:229164", "title": "Possible origin of the bluetongue epidemic in Cyprus, August 1977.", "content": "Possible origins of an epidemic of bluetongue in Cyprus in August 1977 have been analysed. First outbreaks occurred simultaneously in the south-east of the Famagusta district and on the north coast of the Kyrenia district respectively. Although the epidemic was due to type 4, which had been responsible for the previous outbreak in 1969, no evidence of persistance of virus could be found. Imports of domestic animals in the past year were not implicated since the imported cattle were introduced only to the southern part and not to the northern part of the island. Easterly, north-easterly and northerly winds during the period 11-14 August could have brought infected midges at a height of 0.5--1.5 km from Syria and Turkey, and such a movement would fit well the dates of the first outbreaks (20-25 August). Temperatures at a height of 1.5 km were 20-25 degrees C and at 0.5 km 30 35 degrees C, and with wind speeds 10-20 km h-1 the distance from Turkey and Syria would have been covered in 5-20 h. It follows that, in addition to surface winds, winds at all levels warm enough for flight should be taken into account when the possibility of disease spread by windborne midges is being assessed.", "contents": "Possible origin of the bluetongue epidemic in Cyprus, August 1977. Possible origins of an epidemic of bluetongue in Cyprus in August 1977 have been analysed. First outbreaks occurred simultaneously in the south-east of the Famagusta district and on the north coast of the Kyrenia district respectively. Although the epidemic was due to type 4, which had been responsible for the previous outbreak in 1969, no evidence of persistance of virus could be found. Imports of domestic animals in the past year were not implicated since the imported cattle were introduced only to the southern part and not to the northern part of the island. Easterly, north-easterly and northerly winds during the period 11-14 August could have brought infected midges at a height of 0.5--1.5 km from Syria and Turkey, and such a movement would fit well the dates of the first outbreaks (20-25 August). Temperatures at a height of 1.5 km were 20-25 degrees C and at 0.5 km 30 35 degrees C, and with wind speeds 10-20 km h-1 the distance from Turkey and Syria would have been covered in 5-20 h. It follows that, in addition to surface winds, winds at all levels warm enough for flight should be taken into account when the possibility of disease spread by windborne midges is being assessed."}
{"id": "PMID:229165", "title": "Inhibition of human monocyte-macrophage and lymphocyte cytotoxicity to herpes simplex-infected cells by glucan.", "content": "The effect of short term in vitro incubation of glucan--a reticuloendothelial system stimulator--on subsequent cytotoxicity of human monocyte-macrophages (MP) and lymphocytes (L) to Herpes simplex virus-infected cells in a 51Cr-release assay was analyzed. Particulate, cell-associated glucan irreversibly inhibited MP antibody-dependent cellular cytotoxicity (ADCC). In contrast, the inhibition of L-ADCC and L-natural killer cytotoxicity could be reversed by dissociation of glucan and cells utilizing serum gradient centrifugation, a process which did not remove the glucan. These experiments reveal further basic differences between MP and L-ADCC using the reagent glucan.", "contents": "Inhibition of human monocyte-macrophage and lymphocyte cytotoxicity to herpes simplex-infected cells by glucan. The effect of short term in vitro incubation of glucan--a reticuloendothelial system stimulator--on subsequent cytotoxicity of human monocyte-macrophages (MP) and lymphocytes (L) to Herpes simplex virus-infected cells in a 51Cr-release assay was analyzed. Particulate, cell-associated glucan irreversibly inhibited MP antibody-dependent cellular cytotoxicity (ADCC). In contrast, the inhibition of L-ADCC and L-natural killer cytotoxicity could be reversed by dissociation of glucan and cells utilizing serum gradient centrifugation, a process which did not remove the glucan. These experiments reveal further basic differences between MP and L-ADCC using the reagent glucan."}
{"id": "PMID:229166", "title": "Immobilization of viral antigens on filter paper for a [125I]staphylococcal protein A immunoassay: a rapid and sensitive technique for detection of herpes simplex virus antigens and antiviral antibodies.", "content": "A new technique is described for the rapid detection and quantitation of herpes simplex virus (HSV) antigens and antiviral antibodies. It involves immobilization of HSV antigens on filter paper discs and subsequent analysis by 125I-labeled staphylococcal protein A (SPA) radioimmunoassay. A specially designed 96-well filtration device is employed which serves both as an incubation chamber and as a filtration manifold. It is rapid, simple, sensitive and specific, and requires only small volumes of antiserum and few target cells. The results may be readily and objectively quantitated. This technique permits the simultaneous assay of a large number of specimens in less than 1 h. Its sensitivity is considerably greater than that of other currently used immunologic techniques, and it is amenable to automation. These characteristics suggest that this [125I]SPA immunofiltration technique may be applicable to the rapid diagnosis of viral infections.", "contents": "Immobilization of viral antigens on filter paper for a [125I]staphylococcal protein A immunoassay: a rapid and sensitive technique for detection of herpes simplex virus antigens and antiviral antibodies. A new technique is described for the rapid detection and quantitation of herpes simplex virus (HSV) antigens and antiviral antibodies. It involves immobilization of HSV antigens on filter paper discs and subsequent analysis by 125I-labeled staphylococcal protein A (SPA) radioimmunoassay. A specially designed 96-well filtration device is employed which serves both as an incubation chamber and as a filtration manifold. It is rapid, simple, sensitive and specific, and requires only small volumes of antiserum and few target cells. The results may be readily and objectively quantitated. This technique permits the simultaneous assay of a large number of specimens in less than 1 h. Its sensitivity is considerably greater than that of other currently used immunologic techniques, and it is amenable to automation. These characteristics suggest that this [125I]SPA immunofiltration technique may be applicable to the rapid diagnosis of viral infections."}
{"id": "PMID:229170", "title": "Incidence of infectious mononucleosis at the Universities of California and Hawaii.", "content": "The observed rates of heterophil-positive infectious mononucleosis at the University of California at Davis and the University of Hawaii at Manoa were 1,212 and 37 per 100,000 students per academic year, respectively. The data collected suggest that the extraordinarily low incidence at the University of Hawaii may be due to the following factors: (1) underutilization of the student health service by students with infectious mononucleosis; (2) low proportion of Epstein-Barr virus-seronegative students; (3) high proportion of Asian students who appear to be less likely to develop heterophil-positive infectious mononucleosis; and (4) possible low efficiency in the transmission of primary Epstein-Barr virus infections.", "contents": "Incidence of infectious mononucleosis at the Universities of California and Hawaii. The observed rates of heterophil-positive infectious mononucleosis at the University of California at Davis and the University of Hawaii at Manoa were 1,212 and 37 per 100,000 students per academic year, respectively. The data collected suggest that the extraordinarily low incidence at the University of Hawaii may be due to the following factors: (1) underutilization of the student health service by students with infectious mononucleosis; (2) low proportion of Epstein-Barr virus-seronegative students; (3) high proportion of Asian students who appear to be less likely to develop heterophil-positive infectious mononucleosis; and (4) possible low efficiency in the transmission of primary Epstein-Barr virus infections."}
{"id": "PMID:229171", "title": "Specific cell-mediated immunity in children with congenital and neonatal cytomegalovirus infection and their mothers.", "content": "Cell-mediated immunity (CMI) to cytomegalovirus (CMV) and herpes simplex virus type 1 (HSV-1) was examined in 35 mothers and 30 of their offspring with congenital or neonatal CMV infection by means of the lymphocyte transformation assay. Eleven offspring did not respond to CMV antigen, and 15 of the 19 positive children displayed lower responses than those of normal immune adults. Productive infection in the younger children at the time of assay and the presence of disease correlated strongly with the absence of responses. The mothers as a group also demonstrated impaired CMI to CMV while reacting normally to HSV-1 antigen. Neither time after transmission of infection nor viral excretion was significantly associated with impaired CMI, although a trend toward diminished responses was evident among women who were shedding virus. Mitogen stimulation was normal in all test subjects. These findings imply that deficient specific CMI may play a role in the genesis of persistent CMV infection and fetal pathology.", "contents": "Specific cell-mediated immunity in children with congenital and neonatal cytomegalovirus infection and their mothers. Cell-mediated immunity (CMI) to cytomegalovirus (CMV) and herpes simplex virus type 1 (HSV-1) was examined in 35 mothers and 30 of their offspring with congenital or neonatal CMV infection by means of the lymphocyte transformation assay. Eleven offspring did not respond to CMV antigen, and 15 of the 19 positive children displayed lower responses than those of normal immune adults. Productive infection in the younger children at the time of assay and the presence of disease correlated strongly with the absence of responses. The mothers as a group also demonstrated impaired CMI to CMV while reacting normally to HSV-1 antigen. Neither time after transmission of infection nor viral excretion was significantly associated with impaired CMI, although a trend toward diminished responses was evident among women who were shedding virus. Mitogen stimulation was normal in all test subjects. These findings imply that deficient specific CMI may play a role in the genesis of persistent CMV infection and fetal pathology."}
{"id": "PMID:229172", "title": "Impaired cellular immunity to cytomegalovirus in congenitally infected children and their mothers.", "content": "Cell-mediated immunity to cytomegalovirus (CMV) was determined in congenitally infected children and their mothers by use of assays for CMV-specific lymphocyte blastogenesis and interferon production. Six viruric children responded poorly in both assays. Two older nonviruric children responded in the blastogenesis assay, and lymphocytes from one of them produced interferon. Mothers of older children usually responded in the blastogenesis assay, but only one of them produced interferon. Mothers whose infected infants were younger than nine months of age responded poorly in both assays, while control seropositive postpartum women generally responded normally. The cell-mediated immune defects detected in this study may play a role in the pathogenesis of congenital CMV infection.", "contents": "Impaired cellular immunity to cytomegalovirus in congenitally infected children and their mothers. Cell-mediated immunity to cytomegalovirus (CMV) was determined in congenitally infected children and their mothers by use of assays for CMV-specific lymphocyte blastogenesis and interferon production. Six viruric children responded poorly in both assays. Two older nonviruric children responded in the blastogenesis assay, and lymphocytes from one of them produced interferon. Mothers of older children usually responded in the blastogenesis assay, but only one of them produced interferon. Mothers whose infected infants were younger than nine months of age responded poorly in both assays, while control seropositive postpartum women generally responded normally. The cell-mediated immune defects detected in this study may play a role in the pathogenesis of congenital CMV infection."}
{"id": "PMID:229173", "title": "A comparative study of hepatitis B viral markers in the family members of Asian and non-Asian patients with hepatitis B surface antigen-positive hepatocellular carcinoma and with chronic hepatitis B infection.", "content": "Serologic tests for evidence of hepatitis B virus (HBV) infection were performed on family members of Asian and non-Asian patients with either hepatitis B surface antigen (HBsAg)-positive hepatocellular carcinoma or chronic HBV infection. Asian family members had a significant increase of HBsAg (34% higher) and of antibody to HBsAg or of antibody to hepatitis B core antigen (50% higher) when they were compared with non-Asian family members. In the Asian group, viral markers were detected more frequently in blood relatives than in nonblood relatives of the index cases. Within this group, birthplace did not influence the frequency of antigenemia, since HBsAg was positive in 55 (44%) of 125 Asians born in Asia and in 36 (38%) of the 94 Asians who were born in the United States. Also, HBsAg positivity frequently was seen in offspring from HBsAg-positive carrier mothers as well as from HBsAg-positive carrier fathers whose spouses were either HBsAg-negative or who had antibody. The e antigen was found more often in individuals 30 years of age or younger than in older individuals. This study indicates that intrafamilial spread of HBsAg in Asian families plays an important role in the perpetuation of HBV infection and in the eventual development of chronic liver disease in this ethnic group.", "contents": "A comparative study of hepatitis B viral markers in the family members of Asian and non-Asian patients with hepatitis B surface antigen-positive hepatocellular carcinoma and with chronic hepatitis B infection. Serologic tests for evidence of hepatitis B virus (HBV) infection were performed on family members of Asian and non-Asian patients with either hepatitis B surface antigen (HBsAg)-positive hepatocellular carcinoma or chronic HBV infection. Asian family members had a significant increase of HBsAg (34% higher) and of antibody to HBsAg or of antibody to hepatitis B core antigen (50% higher) when they were compared with non-Asian family members. In the Asian group, viral markers were detected more frequently in blood relatives than in nonblood relatives of the index cases. Within this group, birthplace did not influence the frequency of antigenemia, since HBsAg was positive in 55 (44%) of 125 Asians born in Asia and in 36 (38%) of the 94 Asians who were born in the United States. Also, HBsAg positivity frequently was seen in offspring from HBsAg-positive carrier mothers as well as from HBsAg-positive carrier fathers whose spouses were either HBsAg-negative or who had antibody. The e antigen was found more often in individuals 30 years of age or younger than in older individuals. This study indicates that intrafamilial spread of HBsAg in Asian families plays an important role in the perpetuation of HBV infection and in the eventual development of chronic liver disease in this ethnic group."}
{"id": "PMID:229174", "title": "Ocular infection with herpes simplex virus type 1: prevention of acute herpetic encephalitis by systemic administration of virus-specific antibody.", "content": "The effects of virus-specific antibody on the pathogenesis of infection due to herpes simplex virus type 1 (HSV-1) following corneal inoculation of young adult mice were studied. HSV-1 was inoculated onto the corneal surface immediately after trephination with a capillary pipette. After inoculation, virus spread to the trigeminal ganglion and brain within two days and caused acute herpetic encephalitis, which killed infected animals eight to 10 days after infection. Rabbit hyperimmune antisera to HSV-1 were prepared, diluted to contain antibody at a titer of 1:150, and administered intraperitoneally to mice 8 hr after corneal infection. Administration of antisera did not interfere with the spread of HSV-1 from the site of infection to the trigeminal ganglion and brain but did reduce the multiplication of virus within the central nervous system. Reduction in viral replication resulted in complete recovery of the animals that were given antibody to HSV-1. however, the animals were not protected if they were irradiated with 390 rad 24 hr prior to administration of antibody. This observation suggested that antibody-mediated protection was not the result of in vivo neutralization of virus but instead required the presence of antibody as well as one or more radiation-sensitive components.", "contents": "Ocular infection with herpes simplex virus type 1: prevention of acute herpetic encephalitis by systemic administration of virus-specific antibody. The effects of virus-specific antibody on the pathogenesis of infection due to herpes simplex virus type 1 (HSV-1) following corneal inoculation of young adult mice were studied. HSV-1 was inoculated onto the corneal surface immediately after trephination with a capillary pipette. After inoculation, virus spread to the trigeminal ganglion and brain within two days and caused acute herpetic encephalitis, which killed infected animals eight to 10 days after infection. Rabbit hyperimmune antisera to HSV-1 were prepared, diluted to contain antibody at a titer of 1:150, and administered intraperitoneally to mice 8 hr after corneal infection. Administration of antisera did not interfere with the spread of HSV-1 from the site of infection to the trigeminal ganglion and brain but did reduce the multiplication of virus within the central nervous system. Reduction in viral replication resulted in complete recovery of the animals that were given antibody to HSV-1. however, the animals were not protected if they were irradiated with 390 rad 24 hr prior to administration of antibody. This observation suggested that antibody-mediated protection was not the result of in vivo neutralization of virus but instead required the presence of antibody as well as one or more radiation-sensitive components."}
{"id": "PMID:229175", "title": "Lethal effect of complement and lysozyme on polymyxin-treated, serum-resistant gram-negative bacilli.", "content": "When genetically serum-resistant Escherichia coli, Klebsiella pneumoniae, and Citrobacter freundii, but not Pseudomonas aeruginosa or Proteus mirabilis, were exposed to polymyxin B, they became susceptible to the bactericidal action of normal human and rabbit sera. In constrast, beta-lactam and aminoglycoside antibiotics did not render any serum-resistant bacteria serum-sensitive. Synergy between polymyxin B and the serum bactericidal system could be demonstrated by the addition of polymyxin B to bacteria in vitro, as well as to bacilli in serum from rabbits injected with the antibiotic. Polymyxin B-treated bacteria were killed by normal, lysozyme-depleted, C2-deficient, and hypogammaglobulinemic sera, but not by heated or C6-deficient sera. These findings indicate that polymyxin B-treated bacteria can be killed via the alternative complement pathway. However, C3 and C3b were detected on the surface of serum-resistant E. coli, regardless of whether the bacteria had been treated with polymyxin B. This observation suggests that a change in susceptibility to the alternative complement pathway was not the only explanation for the acquired serum sensitivity. Polymyxin B may also affect a step in the complement sequence beyond the activation of C3, a step that is apparently blocked in serum-resistant gram-negative bacteria.", "contents": "Lethal effect of complement and lysozyme on polymyxin-treated, serum-resistant gram-negative bacilli. When genetically serum-resistant Escherichia coli, Klebsiella pneumoniae, and Citrobacter freundii, but not Pseudomonas aeruginosa or Proteus mirabilis, were exposed to polymyxin B, they became susceptible to the bactericidal action of normal human and rabbit sera. In constrast, beta-lactam and aminoglycoside antibiotics did not render any serum-resistant bacteria serum-sensitive. Synergy between polymyxin B and the serum bactericidal system could be demonstrated by the addition of polymyxin B to bacteria in vitro, as well as to bacilli in serum from rabbits injected with the antibiotic. Polymyxin B-treated bacteria were killed by normal, lysozyme-depleted, C2-deficient, and hypogammaglobulinemic sera, but not by heated or C6-deficient sera. These findings indicate that polymyxin B-treated bacteria can be killed via the alternative complement pathway. However, C3 and C3b were detected on the surface of serum-resistant E. coli, regardless of whether the bacteria had been treated with polymyxin B. This observation suggests that a change in susceptibility to the alternative complement pathway was not the only explanation for the acquired serum sensitivity. Polymyxin B may also affect a step in the complement sequence beyond the activation of C3, a step that is apparently blocked in serum-resistant gram-negative bacteria."}
{"id": "PMID:229176", "title": "Indirect immunofluorescence test for detection of IgM antibodies to cytomegalovirus.", "content": "A technique for the detection of IgM antibodies to cytomegalovirus (CMV) by immunofluorescence was developed. In order to prevent interference by rheumatoid factor in the sera, IgG was removed by prior immunoabsorption with antiserum to gamma Fc. Sera from 63 patients with a rise in titer of antibody to CMV, indicated by complement fixation, were IgM-positive, but yielded negative results on the Paul-Bunnell-Davidsohn test for infectious mononucleosis. Convalescent-phase serum samples from 20 patients with a seroconversion to herpes simplex virus and from 20 patients with a seroconversion to varicella-zoster virus also had no IgM antibodies to CMV. Sera from six of 10 patients with infectious mononucleosis and two of 100 normal blood donors were positive for IgM antibodies to CMV. In 38 of 63 patients, the diagnosis of CMV infection could be made several weeks earlier by the immunofluorescence test than by the complement-fixation test. IgM antibodies to CMV persisted for more than two months after onset of symptoms of the infection.", "contents": "Indirect immunofluorescence test for detection of IgM antibodies to cytomegalovirus. A technique for the detection of IgM antibodies to cytomegalovirus (CMV) by immunofluorescence was developed. In order to prevent interference by rheumatoid factor in the sera, IgG was removed by prior immunoabsorption with antiserum to gamma Fc. Sera from 63 patients with a rise in titer of antibody to CMV, indicated by complement fixation, were IgM-positive, but yielded negative results on the Paul-Bunnell-Davidsohn test for infectious mononucleosis. Convalescent-phase serum samples from 20 patients with a seroconversion to herpes simplex virus and from 20 patients with a seroconversion to varicella-zoster virus also had no IgM antibodies to CMV. Sera from six of 10 patients with infectious mononucleosis and two of 100 normal blood donors were positive for IgM antibodies to CMV. In 38 of 63 patients, the diagnosis of CMV infection could be made several weeks earlier by the immunofluorescence test than by the complement-fixation test. IgM antibodies to CMV persisted for more than two months after onset of symptoms of the infection."}
{"id": "PMID:229177", "title": "Antibody to varicella-zoster virus-induced membrane antigen: immunoperoxidase assay with air-dried target cells.", "content": "A technique using indirect immunoperoxidase antibody to membrane antigen (IPAMA) was developed for detection of IgG antibody to varicella-zoster virus (VZV). The IPAMA technique utilizes glass slides with air-dried VZV-infected cells, which can be stored at -70 C and used for several months without loss of sensitivity. Antibody titers measured by the IPAMA technique were comparable to those measured by the technique using indirect fluorescent antibody to membrane antigen (IFAMA) for sera obtained from 63 medical students as well as sera from three patients with chicken pox and nine with herpes-zoster infection, and the sensitivity of the IPAMA was equal to that of the IFAMA technique. No cross-reactivity with antibodies to other herpesviruses was observed.", "contents": "Antibody to varicella-zoster virus-induced membrane antigen: immunoperoxidase assay with air-dried target cells. A technique using indirect immunoperoxidase antibody to membrane antigen (IPAMA) was developed for detection of IgG antibody to varicella-zoster virus (VZV). The IPAMA technique utilizes glass slides with air-dried VZV-infected cells, which can be stored at -70 C and used for several months without loss of sensitivity. Antibody titers measured by the IPAMA technique were comparable to those measured by the technique using indirect fluorescent antibody to membrane antigen (IFAMA) for sera obtained from 63 medical students as well as sera from three patients with chicken pox and nine with herpes-zoster infection, and the sensitivity of the IPAMA was equal to that of the IFAMA technique. No cross-reactivity with antibodies to other herpesviruses was observed."}
{"id": "PMID:229178", "title": "Malignant pleomorphic fibrous histiocytoma of the larynx. (Further observations).", "content": "An exceptional case of pleomorphic malignant fibrous histiocytoma of the larynx occurring in a 68-year-old male patient is reported. A significant histological documentation is given. Problems connected with histogenesis, treatment and prognosis are dealt with. Stress is laid on the need to establish differential diagnosis from other neoplasms, in particular liposarcoma and spindle-cell carcinoma.", "contents": "Malignant pleomorphic fibrous histiocytoma of the larynx. (Further observations). An exceptional case of pleomorphic malignant fibrous histiocytoma of the larynx occurring in a 68-year-old male patient is reported. A significant histological documentation is given. Problems connected with histogenesis, treatment and prognosis are dealt with. Stress is laid on the need to establish differential diagnosis from other neoplasms, in particular liposarcoma and spindle-cell carcinoma."}
{"id": "PMID:229179", "title": "Granular cell myoblastoma in the parotid gland.", "content": "Granular cell myoblastomas develop most commonly in the head and neck region, but their occurrence in the salivary glands has been reported in only one case, in the submaxillary gland. The authors report a case of granular cell myoblastoma in a previously undescribed localization, the parotid gland.", "contents": "Granular cell myoblastoma in the parotid gland. Granular cell myoblastomas develop most commonly in the head and neck region, but their occurrence in the salivary glands has been reported in only one case, in the submaxillary gland. The authors report a case of granular cell myoblastoma in a previously undescribed localization, the parotid gland."}
{"id": "PMID:229181", "title": "Modern trends in surgical treatment of trigeminal neuralgia.", "content": "From 1955 to July 1978, 560 patients suffering from trigeminal neuralgia, who had not responded to medical treatment underwent various alternative procedures. Considering some of these to be out of date, some as showing too high a number of relapses and some as having potentially unjustified risks in an affection in itself not fatal, the authors report only the results observed in a series of 175 patients operated on by retrogasserian rhizotomy according to Frazier (1931), and the results of a series of 184 patients treated by controlled thermocoagulation according to Sweet and Wepsic (1974).", "contents": "Modern trends in surgical treatment of trigeminal neuralgia. From 1955 to July 1978, 560 patients suffering from trigeminal neuralgia, who had not responded to medical treatment underwent various alternative procedures. Considering some of these to be out of date, some as showing too high a number of relapses and some as having potentially unjustified risks in an affection in itself not fatal, the authors report only the results observed in a series of 175 patients operated on by retrogasserian rhizotomy according to Frazier (1931), and the results of a series of 184 patients treated by controlled thermocoagulation according to Sweet and Wepsic (1974)."}
{"id": "PMID:229182", "title": "Effects of surgical stress and corticotrophin on the peripheral metabolism of thyroid hormones in rabbits.", "content": "The effect of surgical stress and ACTH injection on the peripheral monodeiodination of thyroxine (T4) was studied in the rabbit. These stimuli resulted in a switch from the peripheral formation of tri-iodothyronine (T3) to reverse T3 in normal rabbits and in rabbits whose thyroidal secretion was suppressed by administration of T4. This is analogous to the situation in man. These changes were not due to alterations in the serum binding capacity for thyroid hormones.", "contents": "Effects of surgical stress and corticotrophin on the peripheral metabolism of thyroid hormones in rabbits. The effect of surgical stress and ACTH injection on the peripheral monodeiodination of thyroxine (T4) was studied in the rabbit. These stimuli resulted in a switch from the peripheral formation of tri-iodothyronine (T3) to reverse T3 in normal rabbits and in rabbits whose thyroidal secretion was suppressed by administration of T4. This is analogous to the situation in man. These changes were not due to alterations in the serum binding capacity for thyroid hormones."}
{"id": "PMID:229183", "title": "The glycolytic oscillator.", "content": "The glycolytic oscillator, mainly studied in yeast, is described with respect to its overall dynamic and biochemical properties and the kinetics of its master enzyme phosphofructokinase. Biochemical and kinetic analyses are complemented by analysis of mathematical models. In addition to the discussion of structure and function of the glycolytic oscillator under homogeneous spatial conditions, recent theoretical and biochemical experiments demonstrating spatial pattern formation are also discussed, followed by a presentation of physiological viewpoints.", "contents": "The glycolytic oscillator. The glycolytic oscillator, mainly studied in yeast, is described with respect to its overall dynamic and biochemical properties and the kinetics of its master enzyme phosphofructokinase. Biochemical and kinetic analyses are complemented by analysis of mathematical models. In addition to the discussion of structure and function of the glycolytic oscillator under homogeneous spatial conditions, recent theoretical and biochemical experiments demonstrating spatial pattern formation are also discussed, followed by a presentation of physiological viewpoints."}
{"id": "PMID:229185", "title": "A transmissible avian neoplasm. (Sarcoma of the common fowl) by Peyton Rous, M.D., Experimental Medicine for Sept. 1, 1910, vol. 12, pp.696-705.", "content": "In this paper is reported the first avian tumor that has proved transplantable to other individuals. It is a spindle-celled sarcoma of the hen, which thus far has been propagated into its fourth tumor generation. This was accomplished by the use of fowls of pure blood from the small, intimately related stock in which the growth occurred. Market-bought fowls of similar variety have shown themselves insusceptible, as have fowls of mixed breed, pigeons and guinea-pigs. The percentage of successful transplantations has been small, but in the individuals developing a tumor its growth has been fairly rapid. Young chickens are more susceptible than adults. The reinoculation of negative fowls has never resulted in a growth. Throughout, the sarcoma has remained true to type. It is infiltrative and destructive. Metastasis has been observed once (to the heart). Experiments to determine whether the growth may be transmitted by cell-fragments have not yet been made. Repeated bacteriological examinations have yielded negative results. In its general behavior, so far as tested, this avian tumor closely resembles the typical mammalian neoplasms that are transplantable.", "contents": "A transmissible avian neoplasm. (Sarcoma of the common fowl) by Peyton Rous, M.D., Experimental Medicine for Sept. 1, 1910, vol. 12, pp.696-705. In this paper is reported the first avian tumor that has proved transplantable to other individuals. It is a spindle-celled sarcoma of the hen, which thus far has been propagated into its fourth tumor generation. This was accomplished by the use of fowls of pure blood from the small, intimately related stock in which the growth occurred. Market-bought fowls of similar variety have shown themselves insusceptible, as have fowls of mixed breed, pigeons and guinea-pigs. The percentage of successful transplantations has been small, but in the individuals developing a tumor its growth has been fairly rapid. Young chickens are more susceptible than adults. The reinoculation of negative fowls has never resulted in a growth. Throughout, the sarcoma has remained true to type. It is infiltrative and destructive. Metastasis has been observed once (to the heart). Experiments to determine whether the growth may be transmitted by cell-fragments have not yet been made. Repeated bacteriological examinations have yielded negative results. In its general behavior, so far as tested, this avian tumor closely resembles the typical mammalian neoplasms that are transplantable."}
{"id": "PMID:229186", "title": "Absence of allogeneic restriction in human T-cell-mediated cytotoxicity to Epstein-Barr virus-infected target cells. Demonstration of an HLA-linked control at the effector level.", "content": "Peripheral T lymphocytes from patients with infectious mononucleosis (IM) are sensitized in vivo against the Epstein-Barr virus (EBV). The expression of HLA-A, B, or C molecules at the target cell surface is necessary for the cytotoxic reaction because (a) EBV-positive Daudi cells lacking HLA-A, B, and C determinants are resistant to anti-EBV T-cell lysis, (b) cytolysis of EBV-positive target cells can be consistently inhibited by anti-HLA-A, B, and C and anti-beta 2 microglobulin antibodies. However, no evidence for allogeneic restriction in this system was apparent as (a) cytotoxic T lymphocytes (CTL) from one given individual could exert a cytotoxicity of a similar magnitude on different EBV-positive target cells, regardless of the number of HLA-A or B specificities shared by the effectors and targets; (b) CTL from IM patients were able to kill target cells without any HLA-A or B antigen in common; and (c) T5-1 variants lacking one or two HLA antigens at the A, B, or D locus are killed to the same extent as the parental cells. 7 of the 9 IM patients with detectable circulating anti-EBV CTL carried the HLA-A1 antigen, whereas none of the 16 IM patients lacking detectable peripheral CTL were HLA-A1 positive (mean specific lysis of T5-1 target cells by T cells from HLA-A1 positive patients: 29.3 vs. 0.6% in HLA-A1-negative patients) (P less than 10(-9)). These data suggest an HLA-A1-linked gene control of the magnitude of the anti-EBV CTL response. Thus, the HLA region appears to act at two different level sin the T-cell-mediated lysis of EBV-infected cells by controlling first, the development of anti-EBV and second, the expression of HLA-A, B, and C molecules involved as recognition structures at the target cell surface.", "contents": "Absence of allogeneic restriction in human T-cell-mediated cytotoxicity to Epstein-Barr virus-infected target cells. Demonstration of an HLA-linked control at the effector level. Peripheral T lymphocytes from patients with infectious mononucleosis (IM) are sensitized in vivo against the Epstein-Barr virus (EBV). The expression of HLA-A, B, or C molecules at the target cell surface is necessary for the cytotoxic reaction because (a) EBV-positive Daudi cells lacking HLA-A, B, and C determinants are resistant to anti-EBV T-cell lysis, (b) cytolysis of EBV-positive target cells can be consistently inhibited by anti-HLA-A, B, and C and anti-beta 2 microglobulin antibodies. However, no evidence for allogeneic restriction in this system was apparent as (a) cytotoxic T lymphocytes (CTL) from one given individual could exert a cytotoxicity of a similar magnitude on different EBV-positive target cells, regardless of the number of HLA-A or B specificities shared by the effectors and targets; (b) CTL from IM patients were able to kill target cells without any HLA-A or B antigen in common; and (c) T5-1 variants lacking one or two HLA antigens at the A, B, or D locus are killed to the same extent as the parental cells. 7 of the 9 IM patients with detectable circulating anti-EBV CTL carried the HLA-A1 antigen, whereas none of the 16 IM patients lacking detectable peripheral CTL were HLA-A1 positive (mean specific lysis of T5-1 target cells by T cells from HLA-A1 positive patients: 29.3 vs. 0.6% in HLA-A1-negative patients) (P less than 10(-9)). These data suggest an HLA-A1-linked gene control of the magnitude of the anti-EBV CTL response. Thus, the HLA region appears to act at two different level sin the T-cell-mediated lysis of EBV-infected cells by controlling first, the development of anti-EBV and second, the expression of HLA-A, B, and C molecules involved as recognition structures at the target cell surface."}
{"id": "PMID:229187", "title": "In vitro induction of T-lymphocyte-mediated cytotoxicity by infectious murine type C oncornaviruses.", "content": "We have developed a system to induce oncornavirus-specific secondary cytotoxic response in vitro. When Moloney strain of murine sarcoma virus-immune spleen cells were cultivated with purified infectious Moloney murine leukemia virus (M-MuLV) or with supernates of tissue culture cells containing infectious virus, a virus-specific secondary cytotoxic response directed against type-specific determinant(s) of M-MuLV was generated in vitro, as determined by a 4-h 51Cr-release assay. The effector cells were susceptible to the treatment with anti-Thyl.2 plus complement, but were unrelated to natural killer cells (NK), because they could not lyse some target cells specific for M-MuLV in both the induction phase and the interaction between effector cells and target cells. Furthermore, a product of the env gene of M-MuLV, perhaps gp70, appeared to be responsible for this response, because viruses with recombinations in the env gene between ecotropic M-MuLV and a xenotropic virus failed to induce a response. When infectious M-MuLV was exposed to UV-light at different doses, the ability of UV-treated M-MuLV to induce a secondary cytotoxic response decreased in parallel with infectivity, indicating that infectivity was necessary for the induction of this response.", "contents": "In vitro induction of T-lymphocyte-mediated cytotoxicity by infectious murine type C oncornaviruses. We have developed a system to induce oncornavirus-specific secondary cytotoxic response in vitro. When Moloney strain of murine sarcoma virus-immune spleen cells were cultivated with purified infectious Moloney murine leukemia virus (M-MuLV) or with supernates of tissue culture cells containing infectious virus, a virus-specific secondary cytotoxic response directed against type-specific determinant(s) of M-MuLV was generated in vitro, as determined by a 4-h 51Cr-release assay. The effector cells were susceptible to the treatment with anti-Thyl.2 plus complement, but were unrelated to natural killer cells (NK), because they could not lyse some target cells specific for M-MuLV in both the induction phase and the interaction between effector cells and target cells. Furthermore, a product of the env gene of M-MuLV, perhaps gp70, appeared to be responsible for this response, because viruses with recombinations in the env gene between ecotropic M-MuLV and a xenotropic virus failed to induce a response. When infectious M-MuLV was exposed to UV-light at different doses, the ability of UV-treated M-MuLV to induce a secondary cytotoxic response decreased in parallel with infectivity, indicating that infectivity was necessary for the induction of this response."}
{"id": "PMID:229188", "title": "Inhibition of collagen synthesis by mononuclear cell supernates.", "content": "Mononuclear cell infiltration and alteration in the connective tissues are prominent features of the inflammatory response in a number of diseases. To determine whether mononuclear cell products can modulate collagen synthesis, human peripheral mononuclear cells from normal donors were isolated by Ficoll-Hypaque gradient centrifugation and then incubated for 48 h with or without phytohemagglutinin. Confluent cultures of normal, human skin fibroblasts were incubated with [14C]proline and various amounts of dialyzed supernates from the mononuclear cell cultures. Labeled, newly synthesized collagen was estimated by [14C]hydroxyproline analysis, collagenase digestion, and chromatography on Agarose A-5m in sodium dodecyl sulfate. The total incorporation of [14C]proline was not significantly affected by addition of the mononuclear cell supernates, but as much as 90% decrease in the synthesis by the fibroblasts of labeled collagen was found relative to controls. Supernates from the phytohemagglutinin-stimulated cultures were more active than those from nonstimulated cells. These results suggest that mononuclear cells can synthesize a factor(s) which can selectively inhibit collagen synthesis.", "contents": "Inhibition of collagen synthesis by mononuclear cell supernates. Mononuclear cell infiltration and alteration in the connective tissues are prominent features of the inflammatory response in a number of diseases. To determine whether mononuclear cell products can modulate collagen synthesis, human peripheral mononuclear cells from normal donors were isolated by Ficoll-Hypaque gradient centrifugation and then incubated for 48 h with or without phytohemagglutinin. Confluent cultures of normal, human skin fibroblasts were incubated with [14C]proline and various amounts of dialyzed supernates from the mononuclear cell cultures. Labeled, newly synthesized collagen was estimated by [14C]hydroxyproline analysis, collagenase digestion, and chromatography on Agarose A-5m in sodium dodecyl sulfate. The total incorporation of [14C]proline was not significantly affected by addition of the mononuclear cell supernates, but as much as 90% decrease in the synthesis by the fibroblasts of labeled collagen was found relative to controls. Supernates from the phytohemagglutinin-stimulated cultures were more active than those from nonstimulated cells. These results suggest that mononuclear cells can synthesize a factor(s) which can selectively inhibit collagen synthesis."}
{"id": "PMID:229189", "title": "Lymphocyte transformation induced by autologous cells. VIII. Impaired autologous mixed lymphocyte reactivity in patients with acute infectious mononucleosis.", "content": "The autologous mixed lymphocyte reaction (MLR) is severely impaired in patients with acute infectious mononucleosis. Reactivity returned during the course of convalescence. The allogeneic MLR was not impaired in these patients. B cells from patients with infectious mononucleosis do not stimulate autologous T-cell proliferation, and this observation appears to explain the cellular basis of the impaired autologous MLR in infection. Two explanations for the B-cell defect were considered: (a) the influence of serum factors on B-cell function and (b) the effect of Epstein-Barr virus infection.", "contents": "Lymphocyte transformation induced by autologous cells. VIII. Impaired autologous mixed lymphocyte reactivity in patients with acute infectious mononucleosis. The autologous mixed lymphocyte reaction (MLR) is severely impaired in patients with acute infectious mononucleosis. Reactivity returned during the course of convalescence. The allogeneic MLR was not impaired in these patients. B cells from patients with infectious mononucleosis do not stimulate autologous T-cell proliferation, and this observation appears to explain the cellular basis of the impaired autologous MLR in infection. Two explanations for the B-cell defect were considered: (a) the influence of serum factors on B-cell function and (b) the effect of Epstein-Barr virus infection."}
{"id": "PMID:229190", "title": "The role of natural killer cells and antibody-dependent cell-mediated cytotoxicity during murine cytomegalovirus infection.", "content": "Definition of the functions by which the cellular immune system contributes to control of cytomegalovirus (CMV) infection should permit determination of the specific defects which result in the increased susceptibility to infection of immunosuppressed individuals. Using a murine model, we studied the cytotoxic lymphocyte response to murine CMV infection. This response was found to be biphasic. The initial phase extended from the 3rd to the 6th d after infection, was not genetically restricted, and correlated to a rise in numbers of natural killer (NK) and antibody-dependent killer (K) cells in spleens. The NK- and K-cell responses were preceded, by 24 h, by a rise in serum interferon levels, and occurred before the time when antibody could be measured in serum by neutralization. NK and K cells appear to develop the capacity for specific recognition of CMV-infected cells and the potential to contribute to control of the acute phase of CMV infection.", "contents": "The role of natural killer cells and antibody-dependent cell-mediated cytotoxicity during murine cytomegalovirus infection. Definition of the functions by which the cellular immune system contributes to control of cytomegalovirus (CMV) infection should permit determination of the specific defects which result in the increased susceptibility to infection of immunosuppressed individuals. Using a murine model, we studied the cytotoxic lymphocyte response to murine CMV infection. This response was found to be biphasic. The initial phase extended from the 3rd to the 6th d after infection, was not genetically restricted, and correlated to a rise in numbers of natural killer (NK) and antibody-dependent killer (K) cells in spleens. The NK- and K-cell responses were preceded, by 24 h, by a rise in serum interferon levels, and occurred before the time when antibody could be measured in serum by neutralization. NK and K cells appear to develop the capacity for specific recognition of CMV-infected cells and the potential to contribute to control of the acute phase of CMV infection."}
{"id": "PMID:229191", "title": "Expression of endogenous xenotropic retrovirus by methylcholanthrene-induced squamous cell carcinoma of the mouse respiratory tract.", "content": "As a model for human lung cancer, squamous cell carcinomas were induced by 3-methylcholanthrene in mouse tracheas which had been explanted to a subcutaneous site. The tumors that developed were examined for both ecotropic and xenotropic infectious murine leukemia virus (MuLV). From all squamous carcinomas--six out of six--a xenotropic MuLV was isolated. From some of the fibrosarcomas that occurred incidentally in our induction system, ecotropic MuLV was isolated. However, in the fibrosarcomas, no xenotropic MuLV at all was found.", "contents": "Expression of endogenous xenotropic retrovirus by methylcholanthrene-induced squamous cell carcinoma of the mouse respiratory tract. As a model for human lung cancer, squamous cell carcinomas were induced by 3-methylcholanthrene in mouse tracheas which had been explanted to a subcutaneous site. The tumors that developed were examined for both ecotropic and xenotropic infectious murine leukemia virus (MuLV). From all squamous carcinomas--six out of six--a xenotropic MuLV was isolated. From some of the fibrosarcomas that occurred incidentally in our induction system, ecotropic MuLV was isolated. However, in the fibrosarcomas, no xenotropic MuLV at all was found."}
{"id": "PMID:229192", "title": "Cyclic AMP derivatives stimulate the chondrogenic differentiation of the mesoderm subjacent to the apical ectodermal ridge of the chick limb bud.", "content": "Recent studies indicate that one of the major functions of the apical ectodermal ridge (AER) of the embryonic chick limb bud is to maintain mesenchymal cells directly subjacent to it (i.e., cells extending 0.4-0.5 mm from the AER) in a labile, undifferentiated condition. Furthermore, when mesenchymal cells are freed from the AER's influence, either artifically or as a result of normal polarized proximal-to-distal limb outgrowth, they are freed to commence cytodifferentiation. In a preliminary attempt to investigate at a molecular level the mechanism by which the AER exerts its \"negative\" effect on the cytodifferentiation of subridge mesenchymal cells, we have examined the effect of a variety of agents that elevate cyclic AMP levels on the chondrogenic differentiation of the unspecialized subridge mesoderm of the limb bud in an organ culture system. Dibutyryl- and 8-hydroxy-cyclic AMP elicit a dose-dependent increase in the rate and amount of cartilage matrix formation and a corresponding dose-dependent increase in sulfated glycosaminoglycan accumulation by subridge mesoderm explants. The stimulatory effect of suboptimal concentrations of cyclic AMP derivatives is potentiated by the addition of theophylline. The stimulatory effect is limited to cyclic AMP derivatives, since dibutyryl-cyclic GMP and 5'-AMP have no effect. Thus agents that elevate intracellular cyclic AMP levels stimulate the chondrogenic differentiation of the unspecialized subridge mesoderm of the embryonic chick limb bud.", "contents": "Cyclic AMP derivatives stimulate the chondrogenic differentiation of the mesoderm subjacent to the apical ectodermal ridge of the chick limb bud. Recent studies indicate that one of the major functions of the apical ectodermal ridge (AER) of the embryonic chick limb bud is to maintain mesenchymal cells directly subjacent to it (i.e., cells extending 0.4-0.5 mm from the AER) in a labile, undifferentiated condition. Furthermore, when mesenchymal cells are freed from the AER's influence, either artifically or as a result of normal polarized proximal-to-distal limb outgrowth, they are freed to commence cytodifferentiation. In a preliminary attempt to investigate at a molecular level the mechanism by which the AER exerts its \"negative\" effect on the cytodifferentiation of subridge mesenchymal cells, we have examined the effect of a variety of agents that elevate cyclic AMP levels on the chondrogenic differentiation of the unspecialized subridge mesoderm of the limb bud in an organ culture system. Dibutyryl- and 8-hydroxy-cyclic AMP elicit a dose-dependent increase in the rate and amount of cartilage matrix formation and a corresponding dose-dependent increase in sulfated glycosaminoglycan accumulation by subridge mesoderm explants. The stimulatory effect of suboptimal concentrations of cyclic AMP derivatives is potentiated by the addition of theophylline. The stimulatory effect is limited to cyclic AMP derivatives, since dibutyryl-cyclic GMP and 5'-AMP have no effect. Thus agents that elevate intracellular cyclic AMP levels stimulate the chondrogenic differentiation of the unspecialized subridge mesoderm of the embryonic chick limb bud."}
{"id": "PMID:229193", "title": "Interspecific heterokaryons between oocytes and blastomeres of the mouse and the bank vole.", "content": "Interspecific hybrid cells were produced using Sendai-virus-mediated fusion of interphase blastomeres from 2-cell embryos with ovulated oocytes of the mouse and bank vole. Under the influence of the cytoplasm of oocytes (arrested in metaphase II) premature chromosome condensation occurs in the nuclei of blastomeres, thus implying that the cytoplasmic factor which induces chromosome condensation is not species specific, at least not between these two species.", "contents": "Interspecific heterokaryons between oocytes and blastomeres of the mouse and the bank vole. Interspecific hybrid cells were produced using Sendai-virus-mediated fusion of interphase blastomeres from 2-cell embryos with ovulated oocytes of the mouse and bank vole. Under the influence of the cytoplasm of oocytes (arrested in metaphase II) premature chromosome condensation occurs in the nuclei of blastomeres, thus implying that the cytoplasmic factor which induces chromosome condensation is not species specific, at least not between these two species."}
{"id": "PMID:229195", "title": "Light-induced dephosphorylation of two proteins in frog rod outer segments: influence of cyclic nucleotides and calcium.", "content": "Two minor proteins of frog rod outer segments become phosphorylated when retinas are incubated in the dark with 32Pi. The proteins, designated component I (13,000 daltons) and component II (12,000 daltons), are dephosphorylated when retinas are illuminated. The dephosphorylation is reversible; the two proteins are rephosphorylated when illumination ceases. Each outer segment contains approximately 10(6( molecules of components I and II. These remain associated with both fragmented and intact outer segments but dissociate from the outer segment membranes under hypoosmotic conditions. The extent of the light-induced dephosphorylation increases with higher intensities of illumination and is maximal with continuous illumination which bleaches 5.0 x 10(5) rhodopsin molecules/outer segment per second. Light which bleaches 5.0 x 10(3) rhodopsin molecules/outer segment per second causes approximately half-maximal dephosphorylation. This same intermediate level of illumination causes half-suppression of the light-sensitive permeability mechanism in isolated outer segments (Brodie and Bownds. 1976. J. Gen Physiol. 68:1-11) and also induces a half-maximal decrease in their cyclic GMP content (Woodruff et al. 1977. J. Gen. Physiol. 69:667-679). The phosphorylation of components I and II is enhanced by the addition of cyclic GMP or cyclic AMP to either retinas or isolated rod outer segments maintained in the dark. Several pharmacological agents which influence cyclic GMP levels in outer segments, including calcium, cause similar effects on the phosphorylation of components I and II and outer segment permeability. Although the cyclic nucleotide-stimulated phosphorylation can be observed either in retinas or isolated rod outer segments, the light-induced dephosphorylation is observed only in intact retinas.", "contents": "Light-induced dephosphorylation of two proteins in frog rod outer segments: influence of cyclic nucleotides and calcium. Two minor proteins of frog rod outer segments become phosphorylated when retinas are incubated in the dark with 32Pi. The proteins, designated component I (13,000 daltons) and component II (12,000 daltons), are dephosphorylated when retinas are illuminated. The dephosphorylation is reversible; the two proteins are rephosphorylated when illumination ceases. Each outer segment contains approximately 10(6( molecules of components I and II. These remain associated with both fragmented and intact outer segments but dissociate from the outer segment membranes under hypoosmotic conditions. The extent of the light-induced dephosphorylation increases with higher intensities of illumination and is maximal with continuous illumination which bleaches 5.0 x 10(5) rhodopsin molecules/outer segment per second. Light which bleaches 5.0 x 10(3) rhodopsin molecules/outer segment per second causes approximately half-maximal dephosphorylation. This same intermediate level of illumination causes half-suppression of the light-sensitive permeability mechanism in isolated outer segments (Brodie and Bownds. 1976. J. Gen Physiol. 68:1-11) and also induces a half-maximal decrease in their cyclic GMP content (Woodruff et al. 1977. J. Gen. Physiol. 69:667-679). The phosphorylation of components I and II is enhanced by the addition of cyclic GMP or cyclic AMP to either retinas or isolated rod outer segments maintained in the dark. Several pharmacological agents which influence cyclic GMP levels in outer segments, including calcium, cause similar effects on the phosphorylation of components I and II and outer segment permeability. Although the cyclic nucleotide-stimulated phosphorylation can be observed either in retinas or isolated rod outer segments, the light-induced dephosphorylation is observed only in intact retinas."}
{"id": "PMID:229196", "title": "Walk-in patients' decisions about follow-up care.", "content": "This study examined the decisions patients made about obtaining follow-up care after an initial visit to a psychiatric walk-in clinic. Sixty-nine randomly selected patients who received a variety of ambulatory referrals were questioned by means of structured and ured to, and 70 per cent of the patients given medication took it substantially as prescribed. Completion of the referral was associated with being employed, not abusing drugs and alcohol, having a positive view of the walk-in clinic, and adherence to the medication regimen. Referral success was unrelated to sociodemographic characteristics, social integration, the nature of the intended disposition, or prior medical or psychiatric care. Patients who adhered to the disposition did not necessarily adhere to the medication regimen, and vice versa. Referrals were more successful when the patient had preceded the clinical encounter with an active appraisal of his situation. The decision to adhere was a complex and prolonged one in which the patient weighed many factors, of which the physician's suggested disposition was only one.", "contents": "Walk-in patients' decisions about follow-up care. This study examined the decisions patients made about obtaining follow-up care after an initial visit to a psychiatric walk-in clinic. Sixty-nine randomly selected patients who received a variety of ambulatory referrals were questioned by means of structured and ured to, and 70 per cent of the patients given medication took it substantially as prescribed. Completion of the referral was associated with being employed, not abusing drugs and alcohol, having a positive view of the walk-in clinic, and adherence to the medication regimen. Referral success was unrelated to sociodemographic characteristics, social integration, the nature of the intended disposition, or prior medical or psychiatric care. Patients who adhered to the disposition did not necessarily adhere to the medication regimen, and vice versa. Referrals were more successful when the patient had preceded the clinical encounter with an active appraisal of his situation. The decision to adhere was a complex and prolonged one in which the patient weighed many factors, of which the physician's suggested disposition was only one."}
{"id": "PMID:229197", "title": "Neuroendocrine function in long-term pinealectomized male rats, following visual and audiogenic stress.", "content": "Intact, sham-pinealectomized and pinealectomized adult male rats were maintained for 10 weeks on a light : dark (L : D) cycle of 12 : 12,with lights on at 6 a.m. Subsequently they were acutely exposed to (1) visual or (2) audiogenic stress for periods of 2 or 30 min, immediately following which they were decapitated and serum ACTH, corticosterone, FHS, LH, PRL and TSH concentrations were determined. Serum ACTH and corticosterone levels were similar in control and operated groups following both types of stresses. Serum FSH and LH concentrations were elevated in pinealectomized animals as compared to controls, following 30 min of exposure to visual stimulation; no difference in these parameters was observed between the groups following audiogenic stress. Serum PRL levels tended to be lower in pinealectomized animals following both stresses. Serum TSH concentrations following visual stimulation were similar in all groups, but audiogenic stimulation resulted in elevated TSH levels as compared to controls. These data demonstrate that the pineal gland plays an integral role in the responses of the parvicellular neuroendocrine axes to acute neurogenic stress. Possible molecular bases for this involvement are discussed.", "contents": "Neuroendocrine function in long-term pinealectomized male rats, following visual and audiogenic stress. Intact, sham-pinealectomized and pinealectomized adult male rats were maintained for 10 weeks on a light : dark (L : D) cycle of 12 : 12,with lights on at 6 a.m. Subsequently they were acutely exposed to (1) visual or (2) audiogenic stress for periods of 2 or 30 min, immediately following which they were decapitated and serum ACTH, corticosterone, FHS, LH, PRL and TSH concentrations were determined. Serum ACTH and corticosterone levels were similar in control and operated groups following both types of stresses. Serum FSH and LH concentrations were elevated in pinealectomized animals as compared to controls, following 30 min of exposure to visual stimulation; no difference in these parameters was observed between the groups following audiogenic stress. Serum PRL levels tended to be lower in pinealectomized animals following both stresses. Serum TSH concentrations following visual stimulation were similar in all groups, but audiogenic stimulation resulted in elevated TSH levels as compared to controls. These data demonstrate that the pineal gland plays an integral role in the responses of the parvicellular neuroendocrine axes to acute neurogenic stress. Possible molecular bases for this involvement are discussed."}
{"id": "PMID:229198", "title": "Models for ferric cytochrome P450. Characterization of hemin mercaptide complexes by electronic and ESR spectra.", "content": "Hemin coordinated with mercaptide sulfur as fifth ligand and various sixth ligands were investigated as models for cytochrome P450 in its native ferric low-spin state and its ligand complexes. Mixing the hemin with its ligands below -60 degrees C prevented the reduction of the hemin by mercaptide and made it possible to characterize each sample both by electronic and ESR spectra. Excess of mercaptide formed hemin-dimercaptide complexes with hyperporphyrin spectra with two Soret bands around 380 and 370 nm. The second mercaptide could be exchanged by other ligands with hydroxyl, phosphine, thioether, isocyanide, amine, imidazole, and pyridine groups. The comparison of these spectral data with cytochrome P450 substantiates mercaptide as the fifth ligand and makes a hydroxyl group a more likely candidate for the native sixth ligand than an imidazole group.", "contents": "Models for ferric cytochrome P450. Characterization of hemin mercaptide complexes by electronic and ESR spectra. Hemin coordinated with mercaptide sulfur as fifth ligand and various sixth ligands were investigated as models for cytochrome P450 in its native ferric low-spin state and its ligand complexes. Mixing the hemin with its ligands below -60 degrees C prevented the reduction of the hemin by mercaptide and made it possible to characterize each sample both by electronic and ESR spectra. Excess of mercaptide formed hemin-dimercaptide complexes with hyperporphyrin spectra with two Soret bands around 380 and 370 nm. The second mercaptide could be exchanged by other ligands with hydroxyl, phosphine, thioether, isocyanide, amine, imidazole, and pyridine groups. The comparison of these spectral data with cytochrome P450 substantiates mercaptide as the fifth ligand and makes a hydroxyl group a more likely candidate for the native sixth ligand than an imidazole group."}
{"id": "PMID:229199", "title": "Catalysis of the disproportionation of superoxide by metalloporphyrins.", "content": "The efficiencies of several metalloporphyrin complexes at catalyzing the disproportionation of superoxide have been determined at pH 10 in both carbonate and borate buffer systems. Catalytic rate constants were obtained for the iron(III) and cobalt(III) derivatives of tetrakis(4-N-methylpyridyl) porphine, for tetraphenylporphinesulfonatoferrate(III) and for hemin. In addition, the effects of added bovine serum albumin and imidazole were studied. The order of catalytic efficiency is FeTMpyP greater than FeTMpyP(Im)2 greater than FeTPPS(Im)2 approximately FeTPPS approximately FeTPPS.BSA approximately Fe(EDTA) greater than or approximately CoTMpyP greater than hemin(Im)2 greater than or approximately hemin.", "contents": "Catalysis of the disproportionation of superoxide by metalloporphyrins. The efficiencies of several metalloporphyrin complexes at catalyzing the disproportionation of superoxide have been determined at pH 10 in both carbonate and borate buffer systems. Catalytic rate constants were obtained for the iron(III) and cobalt(III) derivatives of tetrakis(4-N-methylpyridyl) porphine, for tetraphenylporphinesulfonatoferrate(III) and for hemin. In addition, the effects of added bovine serum albumin and imidazole were studied. The order of catalytic efficiency is FeTMpyP greater than FeTMpyP(Im)2 greater than FeTPPS(Im)2 approximately FeTPPS approximately FeTPPS.BSA approximately Fe(EDTA) greater than or approximately CoTMpyP greater than hemin(Im)2 greater than or approximately hemin."}
{"id": "PMID:229200", "title": "Ultrastructural basis for different pertechnetate uptake patterns by various human brain tumours.", "content": "Patterns of pertechnetate uptake were correlated with ultrastructural properties of the endothelial wall in 14 human brain tumours. In tumours with reduced uptake of the radionuclide, intercellular tight junctions were observed whereas absence of intercellular tight junctions was characteristic of all tumours with an increased uptake of pertechnetate. In some tumours with increased uptake, fenestrated endothelial wall was seen while in others non-fenestrated wall was evident. We concluded that intercellular junctions and not fenestrations affect the permeability of brain tumours to pertechnetate.", "contents": "Ultrastructural basis for different pertechnetate uptake patterns by various human brain tumours. Patterns of pertechnetate uptake were correlated with ultrastructural properties of the endothelial wall in 14 human brain tumours. In tumours with reduced uptake of the radionuclide, intercellular tight junctions were observed whereas absence of intercellular tight junctions was characteristic of all tumours with an increased uptake of pertechnetate. In some tumours with increased uptake, fenestrated endothelial wall was seen while in others non-fenestrated wall was evident. We concluded that intercellular junctions and not fenestrations affect the permeability of brain tumours to pertechnetate."}
{"id": "PMID:229201", "title": "Morphological, immunocytochemical and biological characteristics of experimental rabbit brain tumors in tissue culture.", "content": "Brain tumors were induced in 3-month-old rabbits of either sex by repeated intravenous injections of N-methyl-N-nitrosourea. Twelve brain tumors (6 pleomorphic gliomas, 5 grade 2--3 astrocytomas, 1 grade 2--3 oligodendroglioma) were established in culture and, with the exception of 2 neoplasms, were propagated in vitro as permanent cell lines. The glial nature of all cell lines was ascertained at several passage levels by testing the cells for the production of S-100 and GFA. It could be shown that most cells of all lines fluoresced positively for the S-100 protein, albeit differences in intensity of fluorescence were clearly noted between cells of the same culture and between different cultures. In general, astrocytoma cell lines had the strongest fluorescence. Pleomorphic glioma cells but especially astrocytoma cells reacted positively also for the GFA protein. Surprisingly enough, isolated cells of the oligodendroglioma line also showed evidence of GFA production. Exposure of cultures of rabbit glioma cells to db-cAMP for 8--10 hr resulted in inhibition of cell proliferation and stimulation of process formation. Furthermore, positive fluorescence for the S-100 and GFA proteins was more intense in cells treated with db-cAMP than in untreated cells. The latter observation may indicate that production and/or accumulation of glial proteins also was enhanced during the stationary phase of cell cultures.", "contents": "Morphological, immunocytochemical and biological characteristics of experimental rabbit brain tumors in tissue culture. Brain tumors were induced in 3-month-old rabbits of either sex by repeated intravenous injections of N-methyl-N-nitrosourea. Twelve brain tumors (6 pleomorphic gliomas, 5 grade 2--3 astrocytomas, 1 grade 2--3 oligodendroglioma) were established in culture and, with the exception of 2 neoplasms, were propagated in vitro as permanent cell lines. The glial nature of all cell lines was ascertained at several passage levels by testing the cells for the production of S-100 and GFA. It could be shown that most cells of all lines fluoresced positively for the S-100 protein, albeit differences in intensity of fluorescence were clearly noted between cells of the same culture and between different cultures. In general, astrocytoma cell lines had the strongest fluorescence. Pleomorphic glioma cells but especially astrocytoma cells reacted positively also for the GFA protein. Surprisingly enough, isolated cells of the oligodendroglioma line also showed evidence of GFA production. Exposure of cultures of rabbit glioma cells to db-cAMP for 8--10 hr resulted in inhibition of cell proliferation and stimulation of process formation. Furthermore, positive fluorescence for the S-100 and GFA proteins was more intense in cells treated with db-cAMP than in untreated cells. The latter observation may indicate that production and/or accumulation of glial proteins also was enhanced during the stationary phase of cell cultures."}
{"id": "PMID:229203", "title": "Involvement of calcium and cyclic AMP in controlling ixodid tick salivary fluid secretion.", "content": "Catecholamine-stimulated salivary fluid secretion (in vitro) by ixodid ticks is reduced by deletion or lowering the concentration of exogenous bathing medium Ca++. The Ca++ antagonist, verapamil, reversibly inhibits dopamine-stimulated secretion. Ionophore A-23187 is unable to induce glands to secrete. Studies in which labeled and unlabeled Ca++ flux were measured indicate that catecholamines induce release of calcium from intracellular stores during secretion. Cyclic AMP/theophylline-stimulated secretion is inhibited by verapamil, and the exclusion of calcium from the support medium. It is concluded that the primary catecholamine stimulus induces cyclic AMP formation and mobilization of Ca++ (intra- and extracellular). Cyclic AMP and calcium are thought to interact to control secretion within the fluid transporting cells of types II and III alveoli.", "contents": "Involvement of calcium and cyclic AMP in controlling ixodid tick salivary fluid secretion. Catecholamine-stimulated salivary fluid secretion (in vitro) by ixodid ticks is reduced by deletion or lowering the concentration of exogenous bathing medium Ca++. The Ca++ antagonist, verapamil, reversibly inhibits dopamine-stimulated secretion. Ionophore A-23187 is unable to induce glands to secrete. Studies in which labeled and unlabeled Ca++ flux were measured indicate that catecholamines induce release of calcium from intracellular stores during secretion. Cyclic AMP/theophylline-stimulated secretion is inhibited by verapamil, and the exclusion of calcium from the support medium. It is concluded that the primary catecholamine stimulus induces cyclic AMP formation and mobilization of Ca++ (intra- and extracellular). Cyclic AMP and calcium are thought to interact to control secretion within the fluid transporting cells of types II and III alveoli."}
{"id": "PMID:229205", "title": "Pathogenicity of axenically cultivated Entamoeba histolytica, strain 200:NIH, in the hamster.", "content": "Entamoeba histolytica strain 200:NIH cultured axenically for about 15 years produced lesions and abscesses in inbred adult hamsters following intrahepatic, intraperitoneal, and intradermal inoculation. These amebae, even in much higher doses, inoculated into the ceca of adult and young hamsters failed to produce lesions or to become established there. On the other hand, 200:NIH axenic amebae passaged through hamster liver (substrain 200:NIH-L) were able to become established and to produce lesions in the ceca of very young hamsters (1- and 3-week-old), the degree of pathogenicity appearing to be inversely proportional to age of the hamster.", "contents": "Pathogenicity of axenically cultivated Entamoeba histolytica, strain 200:NIH, in the hamster. Entamoeba histolytica strain 200:NIH cultured axenically for about 15 years produced lesions and abscesses in inbred adult hamsters following intrahepatic, intraperitoneal, and intradermal inoculation. These amebae, even in much higher doses, inoculated into the ceca of adult and young hamsters failed to produce lesions or to become established there. On the other hand, 200:NIH axenic amebae passaged through hamster liver (substrain 200:NIH-L) were able to become established and to produce lesions in the ceca of very young hamsters (1- and 3-week-old), the degree of pathogenicity appearing to be inversely proportional to age of the hamster."}
{"id": "PMID:229206", "title": "Renal transplantation in patients with bilateral Wilm's tumor.", "content": "Review of cases and of published reports of patients with bilateral Wilms' tumor revealed a significantly higher mortality rate in those who had received a renal transplant than in those who had not. The increased mortality is attributed to overwhelming sepsis resulting from chemotherapy, radiotherapy and immunosuppression. Growth of the tumor did not appear to be accelerated by immunosuppression and transplantation.", "contents": "Renal transplantation in patients with bilateral Wilm's tumor. Review of cases and of published reports of patients with bilateral Wilms' tumor revealed a significantly higher mortality rate in those who had received a renal transplant than in those who had not. The increased mortality is attributed to overwhelming sepsis resulting from chemotherapy, radiotherapy and immunosuppression. Growth of the tumor did not appear to be accelerated by immunosuppression and transplantation."}
{"id": "PMID:229210", "title": "The effects of two analogs of dopamine on ganglionic transmission in the sympathetic nervous system.", "content": "Two aminotetralin analogs of dopamine were studied for their effects on ganglionic transmission in the sympathetic nervous system. Nerve activity (spontaneous firing or evoked action potentials) was recorded on a preganglionic nerve (splanchnic), a mixed nerve (lumbar chain) and several postganglionic nerves (external carotid branch and renal nerve). 6,7-Dihydroxy-2-dimethylaminotetralin and 5,6-dihydroxy-2-dimethylaminotetralin were observed to markedly inhibit spontaneous firing in the renal nerve, external carotid branch and lumbar chain. Splanchnic nerve activity was unaltered, 6,7-Dihydroxy-2-dimethylaminotetralin also depressed evoked responses to submaximal stimulation in the external carotid branch and lumbar chain. These results suggest a ganglionic site of action. Since functional vasomotor activity in the isolated perfused canine forelimb in response to preganglionic nerve stimulation was unaltered, it was concluded that 6,7-dihydroxy-2-dimethylaminotetralin may depress transmission only at certain ganglionic pathways.", "contents": "The effects of two analogs of dopamine on ganglionic transmission in the sympathetic nervous system. Two aminotetralin analogs of dopamine were studied for their effects on ganglionic transmission in the sympathetic nervous system. Nerve activity (spontaneous firing or evoked action potentials) was recorded on a preganglionic nerve (splanchnic), a mixed nerve (lumbar chain) and several postganglionic nerves (external carotid branch and renal nerve). 6,7-Dihydroxy-2-dimethylaminotetralin and 5,6-dihydroxy-2-dimethylaminotetralin were observed to markedly inhibit spontaneous firing in the renal nerve, external carotid branch and lumbar chain. Splanchnic nerve activity was unaltered, 6,7-Dihydroxy-2-dimethylaminotetralin also depressed evoked responses to submaximal stimulation in the external carotid branch and lumbar chain. These results suggest a ganglionic site of action. Since functional vasomotor activity in the isolated perfused canine forelimb in response to preganglionic nerve stimulation was unaltered, it was concluded that 6,7-dihydroxy-2-dimethylaminotetralin may depress transmission only at certain ganglionic pathways."}
{"id": "PMID:229212", "title": "Re-evaluation of the relationship between the positive inotropic effect of ouabain and its inhibitory effect on (Na+ + K+)-dependent adenosine triphosphatase in rabbit and dog hearts.", "content": "Previous studies have shown that in the ouabain-exposed rabbit heart, although positive inotropy and inhibition of (Na+ + K+)-dependent adenosine triphosphatase are induced concomitantly, the extent of inhibition of the enzyme remains constant when positive inotropy is washed out; and in the dog heart, if positive inotropy without arrhythmias is induced by ouabain, inhibition of the enzyme is not detected. The purpose of this work was the re-evaluation of these previous findings. Rapid recovery of the enzyme from small tissue samples was achieved by homogenization in 1 M KCl and centrifugation. When the enzyme was prepared by this method from ouabain-exposed rabbit and dog hearts, ouabain remained bound to the enzyme. The extent of inhibition of the enzyme was measured by the fluorimetric assay of K+-dependent 3-O-methylfluorescein phosphatase before and after removal of bound ouabain. Correlation between the extent of inhibition of this activity and that of (Na+ + K+)-dependent adenosine triphosphatase activity was established. Utilizing these refined methods, the following results were obtained. In the rabbit heart, positive inotropy and enzyme inhibition occurred concomitantly. Washout of the effect resulted in partial reactivation of the enzyme. In the dog heart, the previous findings were confirmed. The results are not inconsistent with the hypothesis that enzyme inhibition is the cause of the positive inotropic effects. They do suggest, however, the need for further testing of the hypothesis.", "contents": "Re-evaluation of the relationship between the positive inotropic effect of ouabain and its inhibitory effect on (Na+ + K+)-dependent adenosine triphosphatase in rabbit and dog hearts. Previous studies have shown that in the ouabain-exposed rabbit heart, although positive inotropy and inhibition of (Na+ + K+)-dependent adenosine triphosphatase are induced concomitantly, the extent of inhibition of the enzyme remains constant when positive inotropy is washed out; and in the dog heart, if positive inotropy without arrhythmias is induced by ouabain, inhibition of the enzyme is not detected. The purpose of this work was the re-evaluation of these previous findings. Rapid recovery of the enzyme from small tissue samples was achieved by homogenization in 1 M KCl and centrifugation. When the enzyme was prepared by this method from ouabain-exposed rabbit and dog hearts, ouabain remained bound to the enzyme. The extent of inhibition of the enzyme was measured by the fluorimetric assay of K+-dependent 3-O-methylfluorescein phosphatase before and after removal of bound ouabain. Correlation between the extent of inhibition of this activity and that of (Na+ + K+)-dependent adenosine triphosphatase activity was established. Utilizing these refined methods, the following results were obtained. In the rabbit heart, positive inotropy and enzyme inhibition occurred concomitantly. Washout of the effect resulted in partial reactivation of the enzyme. In the dog heart, the previous findings were confirmed. The results are not inconsistent with the hypothesis that enzyme inhibition is the cause of the positive inotropic effects. They do suggest, however, the need for further testing of the hypothesis."}
{"id": "PMID:229214", "title": "The kinetics of tubocurarine action and restricted diffusion within the synaptic cleft.", "content": "1. The kinetics of tubocurarine inhibition were studied at the post-synaptic membrane of frog skeletal muscle fibres. Acetylcholine (ACh) and (+)-tubocurarine were ionophoresed from twin-barrel micropipettes, and the membrane potential of the muscle fibre was recorded intracellularly. Tubocurarine-receptor binding was measured by decreases in the response to identical pulses of ACh. 2. The responses to both ACh and tubocurarine had brief latencies and reached their maxima rapidly. It is suggested that under these conditions the kinetics of tubocurarine action are not slowed by diffusion in the space outside the synaptic cleft. 3. After a pulse of tubocurarine, recovery from inhibition proceeds along a roughly exponential time course with a rate constant, 1/tau off approximately equal to 0.5 sec-1. This rate constant does not depend on the maximal level of inhibition and varies only slightly with temperature (Q10 = 1.25). 4. After a sudden maintained increase in tubocurarine release, the ACh responses decrease and eventually reach a new steady-state level. Inhibition develops exponentially with time and the apparent rate constant, 1/tau on, is greater than 1/tau off. When the steady-state inhibition reduces the ACh response to 1/n of its original level, the data are summarized by the relation, 1/tau on = n(1/tau off). 5. When the ACh sensitivity is reduced with cobra toxin, both 1/tau on and 1/tau off increase. Thus, the kinetics of tubocurarine inhibition depend on the density of ACh receptors in the synaptic cleft. 6. After treatment with collagenase, part of the nerve terminal is displaced and the post-synaptic membrane is exposed directly to the external solution. Under these circumstances, 1/tau off increases more than tenfold. 7. Bath-applied tubocurarine competitively inhibits the responses to brief ionophoretic ACh pulses with an apparent equilibrium dissociation constant, K = 0.5 microM. 8. In denervated frog muscle fibres, extrasynaptic receptors have a lower apparent affinity for tubocurarine. After a pulse of tubocurarine, inhibition decays tenfold more rapidly at these extrasynaptic sites than at the synapse. 9. It is suggested that each tubocurarine molecule binds repeatedly to several ACh receptors before escaping from the synaptic from the synaptic cleft and that the probability of this repetitive binding is enhanced because the nerve terminal presents a physical barrier to diffusion out of the cleft. Consequently, the receptor transiently buffer the concentration of tubocurarine in the cleft, and the macroscopic kinetics of inhibition are much slower than the molecular binding rates for tubocurarine.", "contents": "The kinetics of tubocurarine action and restricted diffusion within the synaptic cleft. 1. The kinetics of tubocurarine inhibition were studied at the post-synaptic membrane of frog skeletal muscle fibres. Acetylcholine (ACh) and (+)-tubocurarine were ionophoresed from twin-barrel micropipettes, and the membrane potential of the muscle fibre was recorded intracellularly. Tubocurarine-receptor binding was measured by decreases in the response to identical pulses of ACh. 2. The responses to both ACh and tubocurarine had brief latencies and reached their maxima rapidly. It is suggested that under these conditions the kinetics of tubocurarine action are not slowed by diffusion in the space outside the synaptic cleft. 3. After a pulse of tubocurarine, recovery from inhibition proceeds along a roughly exponential time course with a rate constant, 1/tau off approximately equal to 0.5 sec-1. This rate constant does not depend on the maximal level of inhibition and varies only slightly with temperature (Q10 = 1.25). 4. After a sudden maintained increase in tubocurarine release, the ACh responses decrease and eventually reach a new steady-state level. Inhibition develops exponentially with time and the apparent rate constant, 1/tau on, is greater than 1/tau off. When the steady-state inhibition reduces the ACh response to 1/n of its original level, the data are summarized by the relation, 1/tau on = n(1/tau off). 5. When the ACh sensitivity is reduced with cobra toxin, both 1/tau on and 1/tau off increase. Thus, the kinetics of tubocurarine inhibition depend on the density of ACh receptors in the synaptic cleft. 6. After treatment with collagenase, part of the nerve terminal is displaced and the post-synaptic membrane is exposed directly to the external solution. Under these circumstances, 1/tau off increases more than tenfold. 7. Bath-applied tubocurarine competitively inhibits the responses to brief ionophoretic ACh pulses with an apparent equilibrium dissociation constant, K = 0.5 microM. 8. In denervated frog muscle fibres, extrasynaptic receptors have a lower apparent affinity for tubocurarine. After a pulse of tubocurarine, inhibition decays tenfold more rapidly at these extrasynaptic sites than at the synapse. 9. It is suggested that each tubocurarine molecule binds repeatedly to several ACh receptors before escaping from the synaptic from the synaptic cleft and that the probability of this repetitive binding is enhanced because the nerve terminal presents a physical barrier to diffusion out of the cleft. Consequently, the receptor transiently buffer the concentration of tubocurarine in the cleft, and the macroscopic kinetics of inhibition are much slower than the molecular binding rates for tubocurarine."}
{"id": "PMID:229215", "title": "Effects of some divalent cations on synaptic transmission in frog spinal neurones.", "content": "1. Synaptic transmission between dorsal root afferents and motoneurones was studied in the isolated and hemisected spinal cord of frogs, using intracellular and extracellular recording techniques, and ionic substitutions of divalent cations in the bathing fluid. 2. Delayed components of excitatory post-synaptic potentials (e.p.s.p.s) evoked in motoneurones by dorsal root supramaximal stimuli, as well as the Ca2+-dependent slow after-hyperpolarization which follows antidromic spikes, were reversibly blocked by superfusing the cords with 'Ca2+-free' media containing Co2+ (4 mM) or Mg2+ (6-10 mM). However, short latency e.p.s.p.s persisted in these media for more than 8 hr. 3. The minimum synaptic delay of the Co2+ and Mg2+, resistant e.p.s.p.s, measured from the peak negativity of the extracellularly recorded presynaptic spike to the onset of the e.p.s.p., was 0.3 msec at 10 +/- 1 degrees C. 4. The Co2+, Mg2+-resistant e.p.s.p.s were graded, and could be elicited by stimulation of segmental or adjacent roots. Those evoked by each of two adjacent roots showed linear summation when the roots were stimulated simultaneously. 5. The Co2+, Mg2+-resistant e.p.s.p.s decreased in amplitude at stimulating frequencies between 10 and 100 Hz, and with paired stimuli at intervals shorter than 20-40 msec. These reductions in amplitude were paralleled by decreases in amplitude of the presynaptic population spike. 6. Solutions free of divalent ions, containing EGTA (2 mM) abolished the Co2+, Mg2+-resistant e.p.s.p.s. They remained blocked for a variable time after returning to Ca2+-free Ringer containing Mg2+ (8 mM). Their continued abolition at this stage is probably not due to changes in electrical properties of motoneuronal membranes. Eventually, the Mg2+-resistant e.p.s.p.s started recovering in the Ca2+-free Ringer containing Mg2+. The time of onset of this recovery depended on the duration of exposure to EGTA. 7. Sr2+ (2-11 mM), although less effective than Ca2+, restored the composite e.p.s.p.s evoked by dorsal root supramaximal stimuli, as well as the Ca2+-dependent slow after-hyperpolarization of the motoneurone. The composite e.p.s.p.s could not be restored with Ba2+ (2-10 mM). 8. The results suggest that the Co2+, Mg2+-resistant e.p.s.p is generated by electrical coupling between some afferent fibres (probably primary afferents) and motoneurones. The after-effects of EGTA treatments probably reflect uncoupling of electrotonic junctions. In contrast, the delayed components of the composite e.p.s.p.s are generated through chemical synapses whose divalent cation requirement is similar to that of the neuromuscular junction.", "contents": "Effects of some divalent cations on synaptic transmission in frog spinal neurones. 1. Synaptic transmission between dorsal root afferents and motoneurones was studied in the isolated and hemisected spinal cord of frogs, using intracellular and extracellular recording techniques, and ionic substitutions of divalent cations in the bathing fluid. 2. Delayed components of excitatory post-synaptic potentials (e.p.s.p.s) evoked in motoneurones by dorsal root supramaximal stimuli, as well as the Ca2+-dependent slow after-hyperpolarization which follows antidromic spikes, were reversibly blocked by superfusing the cords with 'Ca2+-free' media containing Co2+ (4 mM) or Mg2+ (6-10 mM). However, short latency e.p.s.p.s persisted in these media for more than 8 hr. 3. The minimum synaptic delay of the Co2+ and Mg2+, resistant e.p.s.p.s, measured from the peak negativity of the extracellularly recorded presynaptic spike to the onset of the e.p.s.p., was 0.3 msec at 10 +/- 1 degrees C. 4. The Co2+, Mg2+-resistant e.p.s.p.s were graded, and could be elicited by stimulation of segmental or adjacent roots. Those evoked by each of two adjacent roots showed linear summation when the roots were stimulated simultaneously. 5. The Co2+, Mg2+-resistant e.p.s.p.s decreased in amplitude at stimulating frequencies between 10 and 100 Hz, and with paired stimuli at intervals shorter than 20-40 msec. These reductions in amplitude were paralleled by decreases in amplitude of the presynaptic population spike. 6. Solutions free of divalent ions, containing EGTA (2 mM) abolished the Co2+, Mg2+-resistant e.p.s.p.s. They remained blocked for a variable time after returning to Ca2+-free Ringer containing Mg2+ (8 mM). Their continued abolition at this stage is probably not due to changes in electrical properties of motoneuronal membranes. Eventually, the Mg2+-resistant e.p.s.p.s started recovering in the Ca2+-free Ringer containing Mg2+. The time of onset of this recovery depended on the duration of exposure to EGTA. 7. Sr2+ (2-11 mM), although less effective than Ca2+, restored the composite e.p.s.p.s evoked by dorsal root supramaximal stimuli, as well as the Ca2+-dependent slow after-hyperpolarization of the motoneurone. The composite e.p.s.p.s could not be restored with Ba2+ (2-10 mM). 8. The results suggest that the Co2+, Mg2+-resistant e.p.s.p is generated by electrical coupling between some afferent fibres (probably primary afferents) and motoneurones. The after-effects of EGTA treatments probably reflect uncoupling of electrotonic junctions. In contrast, the delayed components of the composite e.p.s.p.s are generated through chemical synapses whose divalent cation requirement is similar to that of the neuromuscular junction."}
{"id": "PMID:229216", "title": "Inhibitory effects of cholinergic agents on the release of transmitter at the frog neuromuscular junction.", "content": "1. The cholinesterase inhibitors neostigmine, edrophonium and eserine (7 x 10(-7) M) reduced m.e.p.p. frequency by some 50% at the frog neuromuscular junction. Neostigmine also produced a small reduction in quantal content. 2. Tetraisopropylpyrophosphoramide, with a high specificity for non-specific cholinesterase, has a similar effect on m.e.p.p. frequency but ambenonium, with a high specificity for acetylcholinesterase, was markedly less effective in this respect. 3. Carbachol (10(-5) M) and the muscarinic agonists muscarine and metacholine (7 x 10(-7) M) also reduced the rate of spontaneous release. 4. The action of neostigmine was antagonized by atropine, but not by D-tubocurarine. Muscarine did not have any further effect when m.e.p.p. frequency was reduced with neostigmine. 5. Experiments with reduced extracellular Ca2+ concentration suggest that the cholinergic agents reduce Ca2+ permeability directly at the presynaptic terminals and that they do not act via a change in PNa or PK. It is suggested that the consequent reduction in Ca2+ entry causes a fall in both evoked release and in intracellular Ca2+ concentration, thereby reducing m.e.p.p. frequency. 6. It is concluded that non-specific cholinesterases present on the presynaptic terminals can act as inhibitory muscarinic cholinergic receptors. This form of presynaptic inhibition at the amphibian neuromuscular junction contrasts with that described in the mammalian preparation in which the sites are blocked by D-tubocurarine and are excitatory.", "contents": "Inhibitory effects of cholinergic agents on the release of transmitter at the frog neuromuscular junction. 1. The cholinesterase inhibitors neostigmine, edrophonium and eserine (7 x 10(-7) M) reduced m.e.p.p. frequency by some 50% at the frog neuromuscular junction. Neostigmine also produced a small reduction in quantal content. 2. Tetraisopropylpyrophosphoramide, with a high specificity for non-specific cholinesterase, has a similar effect on m.e.p.p. frequency but ambenonium, with a high specificity for acetylcholinesterase, was markedly less effective in this respect. 3. Carbachol (10(-5) M) and the muscarinic agonists muscarine and metacholine (7 x 10(-7) M) also reduced the rate of spontaneous release. 4. The action of neostigmine was antagonized by atropine, but not by D-tubocurarine. Muscarine did not have any further effect when m.e.p.p. frequency was reduced with neostigmine. 5. Experiments with reduced extracellular Ca2+ concentration suggest that the cholinergic agents reduce Ca2+ permeability directly at the presynaptic terminals and that they do not act via a change in PNa or PK. It is suggested that the consequent reduction in Ca2+ entry causes a fall in both evoked release and in intracellular Ca2+ concentration, thereby reducing m.e.p.p. frequency. 6. It is concluded that non-specific cholinesterases present on the presynaptic terminals can act as inhibitory muscarinic cholinergic receptors. This form of presynaptic inhibition at the amphibian neuromuscular junction contrasts with that described in the mammalian preparation in which the sites are blocked by D-tubocurarine and are excitatory."}
{"id": "PMID:229217", "title": "Materials and methods for cleaning dentures.", "content": "Proper hygienic care of removable dentures is an important means of maintaining a healthy oral mucosa in denture wearers. Denture cleanliness is often poor due to improper mechanical cleansing and the relative inefficiency of most commercial products for chemical cleansing of dentures. Dentists and patients should realize that microbial plaque on dentures may be harmful to both the oral mucosa and the patient's general health. It is the responsibility of the patient to maintain oral hygiene through a daily home care routine. It is the obligation of the dentist to motivate and instruct the patient and provide the means and methods for plaque control. Future research should be directed to developing solution cleansers which can maintain plaque-free dentures with a daily soaking period of 15 to 30 minutes and not affect the color and surface luster of the denture acrylic resin.", "contents": "Materials and methods for cleaning dentures. Proper hygienic care of removable dentures is an important means of maintaining a healthy oral mucosa in denture wearers. Denture cleanliness is often poor due to improper mechanical cleansing and the relative inefficiency of most commercial products for chemical cleansing of dentures. Dentists and patients should realize that microbial plaque on dentures may be harmful to both the oral mucosa and the patient's general health. It is the responsibility of the patient to maintain oral hygiene through a daily home care routine. It is the obligation of the dentist to motivate and instruct the patient and provide the means and methods for plaque control. Future research should be directed to developing solution cleansers which can maintain plaque-free dentures with a daily soaking period of 15 to 30 minutes and not affect the color and surface luster of the denture acrylic resin."}
{"id": "PMID:229218", "title": "A low molecular weight factor from sea urchin eggs elevates sperm cyclic nucleotide concentrations and respiration rates.", "content": "A factor associated with sea urchin eggs that increases sperm cyclic nucleotide concentrations and respiration rates was identified as having a low molecular weight. The factor was more potent at elevating cyclic GMP concentrations than cyclic AMP concentrations, and represents the first demonstration of a factor associated with eggs that is capable of causing elevations of sperm cyclic GMP. Concentration-response curves of the crude mixture of egg factors to increase sperm cyclic AMP and cyclic GMP concentrations and respiratory rates were very similar, and comparable losses of these three activities were observed after extensive dialysis and heat treatment of the crude egg factors. The factor was partly purified by ethanol precipitation of a large molecular weight egg jelly component, and by charcoal adsorption and LH-20 chromatography of the resultant ethanol-soluble material. The factor was not extracted into a variety of organic solvents and had an apparent molecular weight of between 1000 and 2000, as estimated by gel filtration.", "contents": "A low molecular weight factor from sea urchin eggs elevates sperm cyclic nucleotide concentrations and respiration rates. A factor associated with sea urchin eggs that increases sperm cyclic nucleotide concentrations and respiration rates was identified as having a low molecular weight. The factor was more potent at elevating cyclic GMP concentrations than cyclic AMP concentrations, and represents the first demonstration of a factor associated with eggs that is capable of causing elevations of sperm cyclic GMP. Concentration-response curves of the crude mixture of egg factors to increase sperm cyclic AMP and cyclic GMP concentrations and respiratory rates were very similar, and comparable losses of these three activities were observed after extensive dialysis and heat treatment of the crude egg factors. The factor was partly purified by ethanol precipitation of a large molecular weight egg jelly component, and by charcoal adsorption and LH-20 chromatography of the resultant ethanol-soluble material. The factor was not extracted into a variety of organic solvents and had an apparent molecular weight of between 1000 and 2000, as estimated by gel filtration."}
{"id": "PMID:229222", "title": "Troponoids. 3. Synthesis and antiallergy activity of N-troponyloxamic acid esters.", "content": "A number of oxamic acid derivatives of tropones and tropolones were synthesized and their antianaphylactic activity was determined in passive paw anaphylaxis (PPA). Several of these esters possessed oral activity. A comparison of the effect on the biological activity of the esters and the corresponding acid and its salt is reported. The experiments suggesting a relationship between the activity and the bioavailability of the ester 19 are also described. A study of the fate of ester 19 in serum on oral or intravenous administration to rats and dogs is reported. In vitro results of the effect of the compounds 19, 45, and 45a on the activity of the guinea pig lung and beef heart phosphodiesterase are presented. The various factors that may contribute to the antiallergy activity of compounds of this series are discussed.", "contents": "Troponoids. 3. Synthesis and antiallergy activity of N-troponyloxamic acid esters. A number of oxamic acid derivatives of tropones and tropolones were synthesized and their antianaphylactic activity was determined in passive paw anaphylaxis (PPA). Several of these esters possessed oral activity. A comparison of the effect on the biological activity of the esters and the corresponding acid and its salt is reported. The experiments suggesting a relationship between the activity and the bioavailability of the ester 19 are also described. A study of the fate of ester 19 in serum on oral or intravenous administration to rats and dogs is reported. In vitro results of the effect of the compounds 19, 45, and 45a on the activity of the guinea pig lung and beef heart phosphodiesterase are presented. The various factors that may contribute to the antiallergy activity of compounds of this series are discussed."}
{"id": "PMID:229224", "title": "Catecholamine and cyclic nucleotide response of sheep to the injection of Clostridium welchii type D epsilon toxin.", "content": "Injection of Clostridium welchii (C. perfringens) type D epsilon toxin into sheep caused large increases in catecholamine and cyclic adenosine 3',5'-monophosphate levels and moderate increases in cyclic guanosine 3',5'-monophosphate levels. Haemoconcentration also occurred. It is suggested that a rapidly developing brain oedema is the stimulus for a release of catecholamines which in turn activates adenyl cyclase. The resulting rise in cAMP causes glycogenolysis and hyperglycaemia.", "contents": "Catecholamine and cyclic nucleotide response of sheep to the injection of Clostridium welchii type D epsilon toxin. Injection of Clostridium welchii (C. perfringens) type D epsilon toxin into sheep caused large increases in catecholamine and cyclic adenosine 3',5'-monophosphate levels and moderate increases in cyclic guanosine 3',5'-monophosphate levels. Haemoconcentration also occurred. It is suggested that a rapidly developing brain oedema is the stimulus for a release of catecholamines which in turn activates adenyl cyclase. The resulting rise in cAMP causes glycogenolysis and hyperglycaemia."}
{"id": "PMID:229225", "title": "Manganese as a calcium probe: electron paramagnetic resonance and nuclear magnetic resonance spectroscopy of intact cells.", "content": "When Lettree cells are exposed to Mn2+, the cation becomes associated with cells in two ways: in a relatively loose and mobile manner that gives a six-line EPR spectrum designated Mnb*, and in an immobile, relatively tight manner that gives no detectable EPR specrtum, designated Mnb. Mnb* is probably on the surface of cells; most Mnb is probably inside cells. NMR measurements of Lettree cell suspensions show two water proton relaxation rates and confirm the existence of cell-associated Mn. Human erythrocytes, on the other hand, bind no Mn2+ under these conditions, as judged by EPR and NMR measurements. Virally-treated Lettree cells show an increase in Mnb (but not in Mnb*). They also show a third water proton relaxation rate.", "contents": "Manganese as a calcium probe: electron paramagnetic resonance and nuclear magnetic resonance spectroscopy of intact cells. When Lettree cells are exposed to Mn2+, the cation becomes associated with cells in two ways: in a relatively loose and mobile manner that gives a six-line EPR spectrum designated Mnb*, and in an immobile, relatively tight manner that gives no detectable EPR specrtum, designated Mnb. Mnb* is probably on the surface of cells; most Mnb is probably inside cells. NMR measurements of Lettree cell suspensions show two water proton relaxation rates and confirm the existence of cell-associated Mn. Human erythrocytes, on the other hand, bind no Mn2+ under these conditions, as judged by EPR and NMR measurements. Virally-treated Lettree cells show an increase in Mnb (but not in Mnb*). They also show a third water proton relaxation rate."}
{"id": "PMID:229235", "title": "The effect of clays on the oligomerization of HCN.", "content": "The reaction of 0.1 M HCN and dilute solutions of diaminomaleonitrile (DAMN) at pH 8--9 and 25 degrees C in the presence of suspensions of montmorillonite (bentonite) clays were investigated. Montmorillonite clays inhibit the oligomerization of aqueous solutions of HCN. Yields of colored oligomers, ura, and DAMN, are all diminished by clays, but the rate of loss of cyanide is not significantly decreased. The inhibition of oligomer formation is due to the clay-catalyzed decomposition of DAMN. The absence of strong binding of DAMN to clays was suggested by our failure to detect DAMN when a clay that had been incubated with DAMN was washed with spermidine (6 x 10(-3) g/liter). It was established that DAMN does not simply bind to the clays by the observation that the bulk of the radioactivity was recovered from the supernatant in the reaction of 14C-DAMN with montmorillonite. The clay-catalyzed decomposition of DAMN was observed when montmorillonite from two different sources was used and with a variety of homoinic montmorillonites and bentonites. A modification of the established procedure for using the cyanide electrode for cyanide analyses was used to follow the release of HCN from DAMN. This new method can be used in both the acidic and basic pH range and it does not result in the destruction of DAMN by the reagents used for the analysis. Quantitative analyses of the reaction solution from the clay-catalyzed decomposition of DAMN revealed the formation of 1--2 equivalents of HCN per mole of DAMN. The possible significance of these clay-catalyzed reactions in chemical evolution is discussed.", "contents": "The effect of clays on the oligomerization of HCN. The reaction of 0.1 M HCN and dilute solutions of diaminomaleonitrile (DAMN) at pH 8--9 and 25 degrees C in the presence of suspensions of montmorillonite (bentonite) clays were investigated. Montmorillonite clays inhibit the oligomerization of aqueous solutions of HCN. Yields of colored oligomers, ura, and DAMN, are all diminished by clays, but the rate of loss of cyanide is not significantly decreased. The inhibition of oligomer formation is due to the clay-catalyzed decomposition of DAMN. The absence of strong binding of DAMN to clays was suggested by our failure to detect DAMN when a clay that had been incubated with DAMN was washed with spermidine (6 x 10(-3) g/liter). It was established that DAMN does not simply bind to the clays by the observation that the bulk of the radioactivity was recovered from the supernatant in the reaction of 14C-DAMN with montmorillonite. The clay-catalyzed decomposition of DAMN was observed when montmorillonite from two different sources was used and with a variety of homoinic montmorillonites and bentonites. A modification of the established procedure for using the cyanide electrode for cyanide analyses was used to follow the release of HCN from DAMN. This new method can be used in both the acidic and basic pH range and it does not result in the destruction of DAMN by the reagents used for the analysis. Quantitative analyses of the reaction solution from the clay-catalyzed decomposition of DAMN revealed the formation of 1--2 equivalents of HCN per mole of DAMN. The possible significance of these clay-catalyzed reactions in chemical evolution is discussed."}
{"id": "PMID:229236", "title": "Bacterial lipopolysaccharide depresses spontaneous, evoked, and ionophore-induced transmitter release at the neuromuscular junction.", "content": "The neurotoxocity of RNA-free lipopolysaccharide (LPS) extracted from Salmonella Typhimurium (SR-11) was tested at the frog neuromuscular junction using intracellular recording techniques. Spontaneous miniature endplate potential (MEPP) frequency was reduced to 45% of control after 60 minutes in the presence of 10 and 50 micrograms LPS/ml Ringer's solution. Elevation of extracellular [Ca] to 10 mM converted the MEPP frequency response to a biphasic pattern of early acceleration followed by late depression. Evoked endplate potentials (EEPs) were reduced in quantal content until phasic release of transmitter was abolished, while MEPP amplitude and endplate resting potential remained constant. Effects of the potent cation ionophore X537A on MEPP frequency were blocked by 45 minutes of pre-exposure to LPS. Because of its extremely lipophilic character, LPS apparently alters the physical structure of the presynaptic terminal membrane, eventually reducing resting and phasic Ca influx, and isolating the presynaptic terminal from ionophore action.", "contents": "Bacterial lipopolysaccharide depresses spontaneous, evoked, and ionophore-induced transmitter release at the neuromuscular junction. The neurotoxocity of RNA-free lipopolysaccharide (LPS) extracted from Salmonella Typhimurium (SR-11) was tested at the frog neuromuscular junction using intracellular recording techniques. Spontaneous miniature endplate potential (MEPP) frequency was reduced to 45% of control after 60 minutes in the presence of 10 and 50 micrograms LPS/ml Ringer's solution. Elevation of extracellular [Ca] to 10 mM converted the MEPP frequency response to a biphasic pattern of early acceleration followed by late depression. Evoked endplate potentials (EEPs) were reduced in quantal content until phasic release of transmitter was abolished, while MEPP amplitude and endplate resting potential remained constant. Effects of the potent cation ionophore X537A on MEPP frequency were blocked by 45 minutes of pre-exposure to LPS. Because of its extremely lipophilic character, LPS apparently alters the physical structure of the presynaptic terminal membrane, eventually reducing resting and phasic Ca influx, and isolating the presynaptic terminal from ionophore action."}
{"id": "PMID:229237", "title": "Melanotropic peptides: presence in brain of normal and hypophysectomized rats, and subcellularly localized in synaptosomes.", "content": "A major and several minor trichloroacetic acid (TCA) soluble, bioassayable melanotropic peptides, as well as bioreactive and immunoreactive alpha-MSH have been found in the hypothalamus, olfactory bulb and cerebral cortex of normal and hypophysectomized rats. By employing subcellular fractionation procedures it was demonstrated that alpha-MSH and the major TCA soluble melanotropic peptide (MMPB) were localized in synaptosomes and were released by hypoosmotic shock. The analysis of MMPB by electrophoretic and chromatographic procedures reveales that it is not ACTH4-10, ACTH1-10, ACTH1-24, NAcACTH1-10 or alpha-MSH. MMPB was found to cross-react with an antiserum specific for the Lys-Pro-Val NH2 sequence in alpha-MSH, indicating that this C-terminal sequence of alpha-MSH may be present in its structure. MMPB was also shown to differ electrophoretically from the two major TCA soluble melanotropic peptides found in the neurointermediate lobe of the pituitary. In view of their synaptosomal localizations MMPB and alpha-MSH may play a role in synaptic function in the nervous system.", "contents": "Melanotropic peptides: presence in brain of normal and hypophysectomized rats, and subcellularly localized in synaptosomes. A major and several minor trichloroacetic acid (TCA) soluble, bioassayable melanotropic peptides, as well as bioreactive and immunoreactive alpha-MSH have been found in the hypothalamus, olfactory bulb and cerebral cortex of normal and hypophysectomized rats. By employing subcellular fractionation procedures it was demonstrated that alpha-MSH and the major TCA soluble melanotropic peptide (MMPB) were localized in synaptosomes and were released by hypoosmotic shock. The analysis of MMPB by electrophoretic and chromatographic procedures reveales that it is not ACTH4-10, ACTH1-10, ACTH1-24, NAcACTH1-10 or alpha-MSH. MMPB was found to cross-react with an antiserum specific for the Lys-Pro-Val NH2 sequence in alpha-MSH, indicating that this C-terminal sequence of alpha-MSH may be present in its structure. MMPB was also shown to differ electrophoretically from the two major TCA soluble melanotropic peptides found in the neurointermediate lobe of the pituitary. In view of their synaptosomal localizations MMPB and alpha-MSH may play a role in synaptic function in the nervous system."}
{"id": "PMID:229238", "title": "Impedance audiometry: its use in the diagnosis of glomus tympanicum tumors.", "content": "Three cases of glomus tympanicum are presented. The audiological findings are discussed with special emphasis on the results of impedance audiometry. The use of impedance audiometry in the diagnosis and follow-up of glomus tympanicum tumors is suggested.", "contents": "Impedance audiometry: its use in the diagnosis of glomus tympanicum tumors. Three cases of glomus tympanicum are presented. The audiological findings are discussed with special emphasis on the results of impedance audiometry. The use of impedance audiometry in the diagnosis and follow-up of glomus tympanicum tumors is suggested."}
{"id": "PMID:229240", "title": "The genome of infectious bursal disease virus consists of two segments of double-stranded RNA.", "content": "The RNA of infectious bursal disease virus was reexamined in a detailed analysis. It could be established that its genome consists of two segments of double-stranded RNA. The RNA is RNase resistant and has a sedimentation coefficient of 14S and a buoyant density of 1.62 g/ml. The purine/pyrimidine ratio is nearly 1; the guanine plus cytosine content is 55.3%; the Tm is 95.5 degrees C. The molecular weights of the two double-stranded segments were determined to be 2.2 x 10(6) and 2.5 x 10(6).", "contents": "The genome of infectious bursal disease virus consists of two segments of double-stranded RNA. The RNA of infectious bursal disease virus was reexamined in a detailed analysis. It could be established that its genome consists of two segments of double-stranded RNA. The RNA is RNase resistant and has a sedimentation coefficient of 14S and a buoyant density of 1.62 g/ml. The purine/pyrimidine ratio is nearly 1; the guanine plus cytosine content is 55.3%; the Tm is 95.5 degrees C. The molecular weights of the two double-stranded segments were determined to be 2.2 x 10(6) and 2.5 x 10(6)."}
{"id": "PMID:229241", "title": "Epstein-Barr virus DNA is amplified in transformed lymphocytes.", "content": "Leukocytes isolated from two adult donors who lacked detectable antibodies to antigens associated with Epstein-Barr virus were exposed to an average of 0.02 to 0.1 DNA-containing particles of Epstein-Barr virus per cell and immediately clones in agarose. Within about 30 generations all transformed cell clones contained between 5 and 800 copies of viral DNA per cell. Only 1 in 10(4) to less than 1 in 10(5) of the cells of each clone release virus, and the frequency of release did not correlate with the average number of copies of viral DNA in the cells of each clone. One clone that had an average of five copies of viral DNA per cell was recloned, and the average number of copies in four of six subclones increased 15-to 50-fold while the subclones were being propagated sufficiently to study them. These results indicate that Epstein-Barr virus DNA can undergo amplification relative to cell DNA at different times after it transforms cells.", "contents": "Epstein-Barr virus DNA is amplified in transformed lymphocytes. Leukocytes isolated from two adult donors who lacked detectable antibodies to antigens associated with Epstein-Barr virus were exposed to an average of 0.02 to 0.1 DNA-containing particles of Epstein-Barr virus per cell and immediately clones in agarose. Within about 30 generations all transformed cell clones contained between 5 and 800 copies of viral DNA per cell. Only 1 in 10(4) to less than 1 in 10(5) of the cells of each clone release virus, and the frequency of release did not correlate with the average number of copies of viral DNA in the cells of each clone. One clone that had an average of five copies of viral DNA per cell was recloned, and the average number of copies in four of six subclones increased 15-to 50-fold while the subclones were being propagated sufficiently to study them. These results indicate that Epstein-Barr virus DNA can undergo amplification relative to cell DNA at different times after it transforms cells."}
{"id": "PMID:229242", "title": "Roles of the simian virus 40 tumor antigens in transformation of Chinese hamster lung cells: studies with simian virus 40 double mutants.", "content": "Simian virus 40 mutants containing both a tsA mutation (rendering the 90,000 molecular weight [90K] T-antigen thermolabile) and a deletion between 0.54 and 0.59 map units (reducing the size and the amount of the 20K t-antigen) were used to transform Chinese hamster lung cells. The frequencies of transformation by the double mutants were comparable to that of the tsA mutant alone by both the focus and agar assays except when the cells were serum depleted before infection. Growth-arrested cells were transformed (using the agar assay) by the deletion mutants at less than 2% the frequency found when the 20K t-antigen was normal. Growth arrest had very little effect on the temperature sensitivity of the resultant transformed cell lines whether or not the deletion was present.", "contents": "Roles of the simian virus 40 tumor antigens in transformation of Chinese hamster lung cells: studies with simian virus 40 double mutants. Simian virus 40 mutants containing both a tsA mutation (rendering the 90,000 molecular weight [90K] T-antigen thermolabile) and a deletion between 0.54 and 0.59 map units (reducing the size and the amount of the 20K t-antigen) were used to transform Chinese hamster lung cells. The frequencies of transformation by the double mutants were comparable to that of the tsA mutant alone by both the focus and agar assays except when the cells were serum depleted before infection. Growth-arrested cells were transformed (using the agar assay) by the deletion mutants at less than 2% the frequency found when the 20K t-antigen was normal. Growth arrest had very little effect on the temperature sensitivity of the resultant transformed cell lines whether or not the deletion was present."}
{"id": "PMID:229243", "title": "Structural analysis of precursor and product forms of type-common envelope glycoprotein D (CP-1 antigen) of herpes simplex virus type 1.", "content": "The type-common CP-1 antigen of herpes simplex virus type 1 (HSV-1) is associated in the infected cell with two components, a 52,000-molecular-weight glycoprotein (gp52 or pD) and a 59,000-molecular-weight glycoprotein (gp59 or D). The larger form (D) is also found in the virion envelope. It was postulated that pD is a precursor of D. We found that pD shared methionine and arginine tryptic peptides with D isolated from infected cell extracts. D isolated from infected extracts had the same trypric methionine peptide profile as D isolated from the virion envelope. Thus, processing of pD to D does not involve any major alterations in polypeptide structure. Furthermore, D did not share tryptic methionine peptides with the other major glycoproteins of HSV-1. Using [2-3H]mannose as a specific glycoprotein label, we found that pD, which is a basic protein (isoelectric point = 8.0) contained a 1,800-molecular-weight oligomannosyl core moiety and was processed by further glycosylation and sialyation to a more acidic and heterogeneous molecule D, which as a molecular weight of at least 59,000.", "contents": "Structural analysis of precursor and product forms of type-common envelope glycoprotein D (CP-1 antigen) of herpes simplex virus type 1. The type-common CP-1 antigen of herpes simplex virus type 1 (HSV-1) is associated in the infected cell with two components, a 52,000-molecular-weight glycoprotein (gp52 or pD) and a 59,000-molecular-weight glycoprotein (gp59 or D). The larger form (D) is also found in the virion envelope. It was postulated that pD is a precursor of D. We found that pD shared methionine and arginine tryptic peptides with D isolated from infected cell extracts. D isolated from infected extracts had the same trypric methionine peptide profile as D isolated from the virion envelope. Thus, processing of pD to D does not involve any major alterations in polypeptide structure. Furthermore, D did not share tryptic methionine peptides with the other major glycoproteins of HSV-1. Using [2-3H]mannose as a specific glycoprotein label, we found that pD, which is a basic protein (isoelectric point = 8.0) contained a 1,800-molecular-weight oligomannosyl core moiety and was processed by further glycosylation and sialyation to a more acidic and heterogeneous molecule D, which as a molecular weight of at least 59,000."}
{"id": "PMID:229244", "title": "Effect of viral RNase H on the avian sarcoma viral genome during early transcription in vitro.", "content": "We investigated the influence of viral RNase H on the transcription of the avian sarcoma virus RNA in a virion-associated reaction. The ability of RNase H to degrade the RNA moiety of the initially formed RNA-DNA hybrid at the 5' end of the viral genome was found to be greatly dependent on the exact concentration of nonionic detergent used to activate the reaction. At a detergent concentration optimal for extensive and faithful in vitro transcription of avian sarcoma virus RNA by the virion-associated RNA-dependent DNA polymerase, most of the 5' terminus of the RNA was digested in 30 min at 41 degrees C. At higher than optimal detergent concentrations, however, little of that RNA was digested. We conclude that removal of the 5'-terminal redundancy in the RNA after its transcription into DNA is a prerequisite for base pairing of the DNA to the 3'-terminal redundant sequence. Lack of removal of this sequence leads to incorrect elongation and substantial reduction of DNA synthesis. When tested with a synthetic RNA-DNA hybrid, virion-associated RNase H did not reveal a detergent dependence.", "contents": "Effect of viral RNase H on the avian sarcoma viral genome during early transcription in vitro. We investigated the influence of viral RNase H on the transcription of the avian sarcoma virus RNA in a virion-associated reaction. The ability of RNase H to degrade the RNA moiety of the initially formed RNA-DNA hybrid at the 5' end of the viral genome was found to be greatly dependent on the exact concentration of nonionic detergent used to activate the reaction. At a detergent concentration optimal for extensive and faithful in vitro transcription of avian sarcoma virus RNA by the virion-associated RNA-dependent DNA polymerase, most of the 5' terminus of the RNA was digested in 30 min at 41 degrees C. At higher than optimal detergent concentrations, however, little of that RNA was digested. We conclude that removal of the 5'-terminal redundancy in the RNA after its transcription into DNA is a prerequisite for base pairing of the DNA to the 3'-terminal redundant sequence. Lack of removal of this sequence leads to incorrect elongation and substantial reduction of DNA synthesis. When tested with a synthetic RNA-DNA hybrid, virion-associated RNase H did not reveal a detergent dependence."}
{"id": "PMID:229245", "title": "Molecular evidence for a type C retrovirus etiology of the lymphoproliferative disease of turkeys.", "content": "Recently, we isolated from the blood of lymphoproliferative disease (LPD)-affected turkeys a type C retrovirus distinct from the avian leukosis-sarcoma virus complex and the reticuloendotheliosis virus group. We present molecular evidence for the implication of this virus in the LPD of turkeys. Using complementary DNA of LPD viral RNA, we found that the LPD viral genome is specifically and efficiently transcribed (2,500 copies per cell) in LPD tumor cells. Moreover, the LPD tumor cells contained newly inserted LPD viral information (5 to 10 copies per haploid genome), which was not present before the infection. From the absence of LPD virus-specific sequences in the normal cell genome of turkeys, it was concluded that the LPD virus is not an endogenous virus of turkeys. DNA-DNA annealing experiments revealed that the degree of sequence homology between LPD viral complementary DNA and cellular DNA of turkeys was not higher than that between LPD viral complementary DNA and cellular DNA of other species, thus indicating that the virus does not originate from turkeys.", "contents": "Molecular evidence for a type C retrovirus etiology of the lymphoproliferative disease of turkeys. Recently, we isolated from the blood of lymphoproliferative disease (LPD)-affected turkeys a type C retrovirus distinct from the avian leukosis-sarcoma virus complex and the reticuloendotheliosis virus group. We present molecular evidence for the implication of this virus in the LPD of turkeys. Using complementary DNA of LPD viral RNA, we found that the LPD viral genome is specifically and efficiently transcribed (2,500 copies per cell) in LPD tumor cells. Moreover, the LPD tumor cells contained newly inserted LPD viral information (5 to 10 copies per haploid genome), which was not present before the infection. From the absence of LPD virus-specific sequences in the normal cell genome of turkeys, it was concluded that the LPD virus is not an endogenous virus of turkeys. DNA-DNA annealing experiments revealed that the degree of sequence homology between LPD viral complementary DNA and cellular DNA of turkeys was not higher than that between LPD viral complementary DNA and cellular DNA of other species, thus indicating that the virus does not originate from turkeys."}
{"id": "PMID:229246", "title": "New classes of viable deletion mutants in the early region of polyoma virus.", "content": "Viable mutants of polyoma virus have been isolated which have deletions in defined parts of the early region of the genome. One class of mutants has deletions (less than 1% of viral genome length) located between 71.5 and 73.5 on the physical map of polyoma virus DNA, near the origin of replication. These mutants appear to grow and to transform cells in a manner indistinguishable from wild-type virus. A second type of mutant with deletions (about 2% of viral genome length) located between about 88 and 94.5 units on the physical map of polyoma virus DNA have altered transformation properties. One of the latter (which maps between 88 and 91.5 units) also has altered growth characteristics, whereas another (which maps between 91.5 and 94.5 units) resembles wild-type virus in its growth properties. The regions with deleted sequences have been defined by cleaving mutant DNAs with restriction endonucleases and analyzing pyrimidine tracts.", "contents": "New classes of viable deletion mutants in the early region of polyoma virus. Viable mutants of polyoma virus have been isolated which have deletions in defined parts of the early region of the genome. One class of mutants has deletions (less than 1% of viral genome length) located between 71.5 and 73.5 on the physical map of polyoma virus DNA, near the origin of replication. These mutants appear to grow and to transform cells in a manner indistinguishable from wild-type virus. A second type of mutant with deletions (about 2% of viral genome length) located between about 88 and 94.5 units on the physical map of polyoma virus DNA have altered transformation properties. One of the latter (which maps between 88 and 91.5 units) also has altered growth characteristics, whereas another (which maps between 91.5 and 94.5 units) resembles wild-type virus in its growth properties. The regions with deleted sequences have been defined by cleaving mutant DNAs with restriction endonucleases and analyzing pyrimidine tracts."}
{"id": "PMID:229247", "title": "Structural analysis of the genomes of gibbon ape and woolly monkey leukosis viruses.", "content": "Infectious retroviruses have been isolated from gibbon apes and a woolly monkey. Previous studies have shown that these isolates share some antigenic determinants and that they exhibit partial nucleic acid homology. To further define the relationships in this group of viruses, we compared the RNAs of the viruses of the woolly monkey-gibbon ape class by two-dimensional polyacrylamide gel electrophoresis of the large RNase T1-resistant oligonucleotides. The degree of sequence identity between the RNAs was determined by the similarity of the fingerprint patterns and in some cases by partial sequence analysis of individual oligonucleotides. This technique permitted us to determine the degree of sequence identity in related RNA species. These studies showed that as much as 80% of the genomes of gibbon ape leukosis virus-Halls' Island and gibbon ape leukosis virus-brain could be identical. The other viruses, simian sarcoma-associated virus, gibbon ape leukosis virus-Thailand, and gibbon ape leukosis virus-San Francisco, showed an extensive but somewhat lower degree of sequence identity (between 40 to 60% of the genomes.", "contents": "Structural analysis of the genomes of gibbon ape and woolly monkey leukosis viruses. Infectious retroviruses have been isolated from gibbon apes and a woolly monkey. Previous studies have shown that these isolates share some antigenic determinants and that they exhibit partial nucleic acid homology. To further define the relationships in this group of viruses, we compared the RNAs of the viruses of the woolly monkey-gibbon ape class by two-dimensional polyacrylamide gel electrophoresis of the large RNase T1-resistant oligonucleotides. The degree of sequence identity between the RNAs was determined by the similarity of the fingerprint patterns and in some cases by partial sequence analysis of individual oligonucleotides. This technique permitted us to determine the degree of sequence identity in related RNA species. These studies showed that as much as 80% of the genomes of gibbon ape leukosis virus-Halls' Island and gibbon ape leukosis virus-brain could be identical. The other viruses, simian sarcoma-associated virus, gibbon ape leukosis virus-Thailand, and gibbon ape leukosis virus-San Francisco, showed an extensive but somewhat lower degree of sequence identity (between 40 to 60% of the genomes."}
{"id": "PMID:229248", "title": "Structural changes in simian virus 40 chromatin as probed by restriction endonucleases.", "content": "The structure of simian virus 40 (SV40) chromatin was probed by treatment with single- and multiple-site bacterial restriction endonucleases. Approximately the same fraction of the chromatin DNA was cleaved by each of three different single-site endonucleases, indicating that the nucleosomes do not have unique positions with regard to specific nucleotide sequences within the population of chromatin molecules. However, the extent of digestion was found to be strongly influenced by salt concentration. At 100 mM NaCl-5 mM MgCl2, only about 20% of the simian virus 40 (SV40) DNA I in chromatin was converted to linear SV40 DNA III. In contrast, at lower concentrations of NaCl (0.05 or 0.01 M), an additional 20 to 30% of the DNA was cleaved. These results suggest that at 100 mM NaCl only the DNA between nucleosomes was accessible to the restriction enzymes, whereas at the lower salt concentrations, DNA within the nucleosome regions became available for cleavage. Surprisingly, when SV40 chromatin was digested with multiple-site restriction enzymes, less than 2% of the DNA was digested to limit digest fragment, whereas only a small fraction (9 to 15%) received two or more cuts. Instead, the principal digest fragment was full-length linear SV40 DNA III. The failure to generate limit digest fragments was not a consequence of reduced enzyme activity in the reaction mixtures or of histone exchange. When the position of the principal cleavage site was mapped after HpaI digestion, it was found that this site was not unique. Nevertheless, all sites wree not cleaved with equal probability. An additional finding was that SV40 chromatin containing nicked-circular DNA II produced by random nicking of DNA I was also resistant to digestion by restriction enzymes. These results suggest that the initial cut which causes relaxation of topological constraint in SV40 chromatin DNA imparts resistance to further digestion by restriction enzymes. We propose that this may be accomplished by either \"winding\" of the internucleosomal DNA into the body of the nucleosome, or as suggested by others, by successive right-hand rotation of nucleosomes.", "contents": "Structural changes in simian virus 40 chromatin as probed by restriction endonucleases. The structure of simian virus 40 (SV40) chromatin was probed by treatment with single- and multiple-site bacterial restriction endonucleases. Approximately the same fraction of the chromatin DNA was cleaved by each of three different single-site endonucleases, indicating that the nucleosomes do not have unique positions with regard to specific nucleotide sequences within the population of chromatin molecules. However, the extent of digestion was found to be strongly influenced by salt concentration. At 100 mM NaCl-5 mM MgCl2, only about 20% of the simian virus 40 (SV40) DNA I in chromatin was converted to linear SV40 DNA III. In contrast, at lower concentrations of NaCl (0.05 or 0.01 M), an additional 20 to 30% of the DNA was cleaved. These results suggest that at 100 mM NaCl only the DNA between nucleosomes was accessible to the restriction enzymes, whereas at the lower salt concentrations, DNA within the nucleosome regions became available for cleavage. Surprisingly, when SV40 chromatin was digested with multiple-site restriction enzymes, less than 2% of the DNA was digested to limit digest fragment, whereas only a small fraction (9 to 15%) received two or more cuts. Instead, the principal digest fragment was full-length linear SV40 DNA III. The failure to generate limit digest fragments was not a consequence of reduced enzyme activity in the reaction mixtures or of histone exchange. When the position of the principal cleavage site was mapped after HpaI digestion, it was found that this site was not unique. Nevertheless, all sites wree not cleaved with equal probability. An additional finding was that SV40 chromatin containing nicked-circular DNA II produced by random nicking of DNA I was also resistant to digestion by restriction enzymes. These results suggest that the initial cut which causes relaxation of topological constraint in SV40 chromatin DNA imparts resistance to further digestion by restriction enzymes. We propose that this may be accomplished by either \"winding\" of the internucleosomal DNA into the body of the nucleosome, or as suggested by others, by successive right-hand rotation of nucleosomes."}
{"id": "PMID:229249", "title": "Gene expression of herpes simplex virus. I. Analysis of cytoplasmic RNAs in infected xeroderma pigmentosum cells.", "content": "RNAs which are synthesized and accumulate in the cytoplasm of uninfected and herpes simplex virus type 1 (HSV-1)-infected xeroderma pigmentosum (XP) cells in the presence of cycloheximide (early RNAs) or absence of drugs (late RNAs) were analyzed by electrophoresis through denaturing polyacrylamide gradient slab gels. HSV RNAs were selected by hybridization ot HSV DNA covalently bound to cellulose. No HSV-specific low-molecular-weight (4S to 10S) RNAs were detected. However, several changes were observed in the electrophoretic pattern of the host low-molecular-weight RNAs during HSV infection. Five HSV RNAs ranging in size from 16S to 28S accumulated in the cytoplasm of infected XP cells in the presence of cycloheximide. These are of the size range predicted to encode the major early viral polypeptides. The cytoplasmic and polyadenylated early RNAs from HSV-infected XP cells were translated in vitro to produce proteins whose electrophoretic pattern resembled that of the early viral proteins synthesized in vivo.", "contents": "Gene expression of herpes simplex virus. I. Analysis of cytoplasmic RNAs in infected xeroderma pigmentosum cells. RNAs which are synthesized and accumulate in the cytoplasm of uninfected and herpes simplex virus type 1 (HSV-1)-infected xeroderma pigmentosum (XP) cells in the presence of cycloheximide (early RNAs) or absence of drugs (late RNAs) were analyzed by electrophoresis through denaturing polyacrylamide gradient slab gels. HSV RNAs were selected by hybridization ot HSV DNA covalently bound to cellulose. No HSV-specific low-molecular-weight (4S to 10S) RNAs were detected. However, several changes were observed in the electrophoretic pattern of the host low-molecular-weight RNAs during HSV infection. Five HSV RNAs ranging in size from 16S to 28S accumulated in the cytoplasm of infected XP cells in the presence of cycloheximide. These are of the size range predicted to encode the major early viral polypeptides. The cytoplasmic and polyadenylated early RNAs from HSV-infected XP cells were translated in vitro to produce proteins whose electrophoretic pattern resembled that of the early viral proteins synthesized in vivo."}
{"id": "PMID:229250", "title": "Heteroduplex analysis of the sequence relationships between the genomes of Kirsten and Harvey sarcoma viruses, their respective parental murine leukemia viruses, and the rat endogenous 30S RNA.", "content": "The sequence relations between Kirsten murine sarcoma virus (Ki-SV), Harvey murine sarcoma virus (Ha-SV), and a rat endogenous 30S RNA were studied by electron microscope heteroduplex analysis. The sequence relationships between the sarcoma viruses and their respective parental murine leukemia viruses (Kirsten and Moloney murine leukemia viruses), as well as between the two murine leukemia viruses, were also studied. The only observed nonhomology feature of the Kirsten murine leukemia virus/Moloney murine leukemia virus heteroduplexes was a substitution loop with two arms of equal length extending from 1.80 +/- 0.18 kilobases (kb) to 2.65 +/- 0.27 kb from the 3' end of the RNA. It is believed that this feature lies in the env gene region of the viral genomes. The Ha-SV and Moloney murine leukemia virus genomes (respective lengths, 6.0 and 9.0 kb) were homologous in a 1.0 +/- 0.05-kb region at the 3' end and possibly over a 200-nucleotide region at the 5' ends; otherwise, they were nonhomologous. Ha-SV and Ki-SV (length, 7.5 kb) were homologous in the first 4.36 +/- 0.37-kb region from the 3' end and in a 0.70 +/- 0.15-kb region at the 5' end. In between, there was a nonhomology region, possibly containing a short (0.23-kb) region of partial or total homology. The heteroduplex analysis between rat endogenous 30S RNA and Ki-SV shows that there are mixed regions of sequence homology and nonhomology at both the 5' and 3' ends. However, there is a large (4-kb) region of homology between Ki-SV and the rat 30S RNA in the center of the genomes, with only a small nonhomology hairpin feature. These studies help to define the regions of homology between the Ha-SV and Ki-SV genomes with each other and with the rat endogenous 30S RNA. These regions may be related to the sarcoma genicity of the viruses. In particular, the 0.7-kb region of homology of Ha-SV with Ki-SV at the 5' ends may be related to the formation of a 21,000-dalton phosphoprotein in cells transformed by either virus.", "contents": "Heteroduplex analysis of the sequence relationships between the genomes of Kirsten and Harvey sarcoma viruses, their respective parental murine leukemia viruses, and the rat endogenous 30S RNA. The sequence relations between Kirsten murine sarcoma virus (Ki-SV), Harvey murine sarcoma virus (Ha-SV), and a rat endogenous 30S RNA were studied by electron microscope heteroduplex analysis. The sequence relationships between the sarcoma viruses and their respective parental murine leukemia viruses (Kirsten and Moloney murine leukemia viruses), as well as between the two murine leukemia viruses, were also studied. The only observed nonhomology feature of the Kirsten murine leukemia virus/Moloney murine leukemia virus heteroduplexes was a substitution loop with two arms of equal length extending from 1.80 +/- 0.18 kilobases (kb) to 2.65 +/- 0.27 kb from the 3' end of the RNA. It is believed that this feature lies in the env gene region of the viral genomes. The Ha-SV and Moloney murine leukemia virus genomes (respective lengths, 6.0 and 9.0 kb) were homologous in a 1.0 +/- 0.05-kb region at the 3' end and possibly over a 200-nucleotide region at the 5' ends; otherwise, they were nonhomologous. Ha-SV and Ki-SV (length, 7.5 kb) were homologous in the first 4.36 +/- 0.37-kb region from the 3' end and in a 0.70 +/- 0.15-kb region at the 5' end. In between, there was a nonhomology region, possibly containing a short (0.23-kb) region of partial or total homology. The heteroduplex analysis between rat endogenous 30S RNA and Ki-SV shows that there are mixed regions of sequence homology and nonhomology at both the 5' and 3' ends. However, there is a large (4-kb) region of homology between Ki-SV and the rat 30S RNA in the center of the genomes, with only a small nonhomology hairpin feature. These studies help to define the regions of homology between the Ha-SV and Ki-SV genomes with each other and with the rat endogenous 30S RNA. These regions may be related to the sarcoma genicity of the viruses. In particular, the 0.7-kb region of homology of Ha-SV with Ki-SV at the 5' ends may be related to the formation of a 21,000-dalton phosphoprotein in cells transformed by either virus."}
{"id": "PMID:229251", "title": "Persistence of the cytomegalovirus genome in human cells.", "content": "A small percentage of human fibroblast cells survived high-multiplicity infection by cytomegalovirus and were isolated as persistently infected cultures. Approximately 30% of the cells were in the productive phase of infection, since virus-specific structural antigens and virions were associated with these cells. The remaining cells contained neither viral structural antigens nor particles. Nuclear DNA from these nonproductive cells contained approximately 120 genome equivalents of viral DNA per cell as determined by reassociation kinetics. In situ hybridization confirmed that nuclei from nonproductive cells contained a significant amount of viral DNA that was distributed in most of these cells. Early virus-induced proteins and antigens were also detected. Nonproductive cells continued to grow, and there was a slow, spontaneous transition of some of these cells to productive viral replication. The majority of the viral DNA in nonproductive cells persisted with restricted gene expression. When infectious virus production was eliminated by growing the persistently infected cultures in the presence of anticytomegalovirus serum, approximately 45 genome equivalents of the viral DNA persisted per cell. The reassociation reaction approached completion. After removal of the antiserum and subculturing, infectious virus production resumed. Therefore, it was assumed that all sequences of the viral genome remained associated with these cells. Restriction of cytomegalovirus gene expression in persistently infected cell cultures is discussed.", "contents": "Persistence of the cytomegalovirus genome in human cells. A small percentage of human fibroblast cells survived high-multiplicity infection by cytomegalovirus and were isolated as persistently infected cultures. Approximately 30% of the cells were in the productive phase of infection, since virus-specific structural antigens and virions were associated with these cells. The remaining cells contained neither viral structural antigens nor particles. Nuclear DNA from these nonproductive cells contained approximately 120 genome equivalents of viral DNA per cell as determined by reassociation kinetics. In situ hybridization confirmed that nuclei from nonproductive cells contained a significant amount of viral DNA that was distributed in most of these cells. Early virus-induced proteins and antigens were also detected. Nonproductive cells continued to grow, and there was a slow, spontaneous transition of some of these cells to productive viral replication. The majority of the viral DNA in nonproductive cells persisted with restricted gene expression. When infectious virus production was eliminated by growing the persistently infected cultures in the presence of anticytomegalovirus serum, approximately 45 genome equivalents of the viral DNA persisted per cell. The reassociation reaction approached completion. After removal of the antiserum and subculturing, infectious virus production resumed. Therefore, it was assumed that all sequences of the viral genome remained associated with these cells. Restriction of cytomegalovirus gene expression in persistently infected cell cultures is discussed."}
{"id": "PMID:229252", "title": "Molecular cloning of the Harvey sarcoma virus closed circular DNA intermediates: initial structural and biological characterization.", "content": "Supercoiled Harvey sarcoma virus (Ha-SV) DNA was extracted from newly infected cells by the Hirt procedure, enriched by preparative agarose gel electrophoresis, and digested with EcoRI, which cleaved the viral DNA at a unique site. The linearized Ha-SV DNA was then inserted into lambda gtWESlambda B at the EcoRI site and cloned in an approved EK2 host. Ha-SV DNA inserts from six independently derived recombinant clones have been analyzed by restriction endonuclease digestion, molecular hybridization, electron microscopy, and infectivity. Four of the Ha-SV DNA inserts were identical, contained about 6.0 kilobase pairs (kbp), and comigrated in agarose gels with the infectious, unintegrated, linear Ha-SV DNA. One insert was approximately 0.65 kbp smaller (5.35 kbp) and one was approximately 0.65 kpb larger (6.65 kpb) than the 6.0 kpb inserts. R-looping with Ha-SV RNA revealed that the small (5.35 kbp) insert contained one copy of the Ha-SV RNA. Preliminary restriction endonuclease digestion of the recombinant DNAs suggested that the middle-size inserts contained a 0.65-kbp tandem duplication of sequences present only one in the small-size insert; this duplication corresponded to the 0.65-kpb terminal duplication of the unintegrated linear Ha-SV DNA. The large-size insert apparently contained a tandem triplication of these terminally located sequences. DNA of all three sized inserts induced foci in NIH 3T3 cells, and focus-forming activity could be rescued from the transformed cells by superinfection with helper virus. Infectivity followed single-hit kinetics, suggesting that the foci were induced by a single molecule.", "contents": "Molecular cloning of the Harvey sarcoma virus closed circular DNA intermediates: initial structural and biological characterization. Supercoiled Harvey sarcoma virus (Ha-SV) DNA was extracted from newly infected cells by the Hirt procedure, enriched by preparative agarose gel electrophoresis, and digested with EcoRI, which cleaved the viral DNA at a unique site. The linearized Ha-SV DNA was then inserted into lambda gtWESlambda B at the EcoRI site and cloned in an approved EK2 host. Ha-SV DNA inserts from six independently derived recombinant clones have been analyzed by restriction endonuclease digestion, molecular hybridization, electron microscopy, and infectivity. Four of the Ha-SV DNA inserts were identical, contained about 6.0 kilobase pairs (kbp), and comigrated in agarose gels with the infectious, unintegrated, linear Ha-SV DNA. One insert was approximately 0.65 kbp smaller (5.35 kbp) and one was approximately 0.65 kpb larger (6.65 kpb) than the 6.0 kpb inserts. R-looping with Ha-SV RNA revealed that the small (5.35 kbp) insert contained one copy of the Ha-SV RNA. Preliminary restriction endonuclease digestion of the recombinant DNAs suggested that the middle-size inserts contained a 0.65-kbp tandem duplication of sequences present only one in the small-size insert; this duplication corresponded to the 0.65-kpb terminal duplication of the unintegrated linear Ha-SV DNA. The large-size insert apparently contained a tandem triplication of these terminally located sequences. DNA of all three sized inserts induced foci in NIH 3T3 cells, and focus-forming activity could be rescued from the transformed cells by superinfection with helper virus. Infectivity followed single-hit kinetics, suggesting that the foci were induced by a single molecule."}
{"id": "PMID:229253", "title": "Simian rotavirus SA11 replication in cell cultures.", "content": "Understanding the basic virology of rotavirus infections has been hampered by the fastidiousness of most isolates and by the lack of a rapid quantitative assay method. The growth characteristics of the simian rotavirus SA11 were studied because it grows to high titers in tissue culture and infectivity can be quantitated by plaque assay. SA11 replication was analyzed in a variety of primary cell cultures or continuous cell lines derived from both homologous and heterologous hosts. Viral replication was observed in each of the cell cultured examined. The individual cell cultures demonstrated marked variability in their susceptibility to rotavirus infection. The highest titers were obtained with MA104, BSC-1, CV-1, and BGM cells. Observable cytopathic effect was found to correlate with the percentage of infected cells in the culture. This study presents growth curves of the simian rotavirus in a variety of cell cultures.", "contents": "Simian rotavirus SA11 replication in cell cultures. Understanding the basic virology of rotavirus infections has been hampered by the fastidiousness of most isolates and by the lack of a rapid quantitative assay method. The growth characteristics of the simian rotavirus SA11 were studied because it grows to high titers in tissue culture and infectivity can be quantitated by plaque assay. SA11 replication was analyzed in a variety of primary cell cultures or continuous cell lines derived from both homologous and heterologous hosts. Viral replication was observed in each of the cell cultured examined. The individual cell cultures demonstrated marked variability in their susceptibility to rotavirus infection. The highest titers were obtained with MA104, BSC-1, CV-1, and BGM cells. Observable cytopathic effect was found to correlate with the percentage of infected cells in the culture. This study presents growth curves of the simian rotavirus in a variety of cell cultures."}
{"id": "PMID:229254", "title": "The 55K protein on the 5' termini of adenovirus type 2 DNA is unrelated to virus-coded candidate transformation proteins (E1-53K, E1-40K-50K) and DNA-binding proteins (E2-42K/47K/73K).", "content": "A polypeptide of 55,000 daltons (55K) is linked, probably covalently, to the K' termini of adenovirus type 2 DNA. The 55K polypeptide is synthesized during early stages of infection (T. Yamashita, M. Arens, and M. Green, J. Virol. 30: 497-507, 1979) and thus may function in viral DNA replication, gene regulation, or cell transformation. Several virus-coded early polypeptides have been identified that could correspond to the terminal 55K, including the E1-40K-50K and E1-53K candidate transformation polypeptides and the E2-42K/47K/73K single-stranded DNA-binding polypeptide. We show here that two-dimensional tryptic [35S]methionine-peptide maps of the terminal 55K differ completely from [35S]methionine-peptide maps of four related E1-40K-50K polypeptides, the E1-53K, and the related E2-42K, E2-47K, and E2-73K polypeptides. We conclude that the terminal 55K polypeptide does not correspond to any of the known virus-coded early polypeptides.", "contents": "The 55K protein on the 5' termini of adenovirus type 2 DNA is unrelated to virus-coded candidate transformation proteins (E1-53K, E1-40K-50K) and DNA-binding proteins (E2-42K/47K/73K). A polypeptide of 55,000 daltons (55K) is linked, probably covalently, to the K' termini of adenovirus type 2 DNA. The 55K polypeptide is synthesized during early stages of infection (T. Yamashita, M. Arens, and M. Green, J. Virol. 30: 497-507, 1979) and thus may function in viral DNA replication, gene regulation, or cell transformation. Several virus-coded early polypeptides have been identified that could correspond to the terminal 55K, including the E1-40K-50K and E1-53K candidate transformation polypeptides and the E2-42K/47K/73K single-stranded DNA-binding polypeptide. We show here that two-dimensional tryptic [35S]methionine-peptide maps of the terminal 55K differ completely from [35S]methionine-peptide maps of four related E1-40K-50K polypeptides, the E1-53K, and the related E2-42K, E2-47K, and E2-73K polypeptides. We conclude that the terminal 55K polypeptide does not correspond to any of the known virus-coded early polypeptides."}
{"id": "PMID:229255", "title": "Regulation of persistent infection with herpes simplex virus in vitro by hydrocortisone.", "content": "About 1% of Raji cells showed sensitivity to herpes simplex virus type 2 (HSV-2) infection when tested by infectious center assays or immunofluorescence tests, and the percentage did not change during cell passage. The addition of hydrocortisone to Raji cells persistently infected with HSV-2 caused a marked increase in virus production and in the number of HSV-producing cells. In the case of HSV-1, it was shown that the addition of hydrocortisone was required to maintain persistent infection. These observations suggest that control of replication of HSV-1 and HSV-2 in these cells is regulated by different mechanisms.", "contents": "Regulation of persistent infection with herpes simplex virus in vitro by hydrocortisone. About 1% of Raji cells showed sensitivity to herpes simplex virus type 2 (HSV-2) infection when tested by infectious center assays or immunofluorescence tests, and the percentage did not change during cell passage. The addition of hydrocortisone to Raji cells persistently infected with HSV-2 caused a marked increase in virus production and in the number of HSV-producing cells. In the case of HSV-1, it was shown that the addition of hydrocortisone was required to maintain persistent infection. These observations suggest that control of replication of HSV-1 and HSV-2 in these cells is regulated by different mechanisms."}
{"id": "PMID:229256", "title": "Comparative study of different isolates of murine sarcoma virus.", "content": "The RNA genomes of a variety of murine sarcoma viruses (MSV) were compared by heteroduplex analysis. These viruses included the Moloney-derived isolates 124-MSV, m1-MSV, m3-MSV, HT1-MSV, and NP-MSV and also two independent isolates, Gazdar MSV and 1712-MSV. All of these viral genomes exhibited the acquired cellular sequences previously identified in 3124-MSV and thought to be responsible for transformation and sarcomagenesis. The location of the acquired cellular sequences within the envelope gene was variable in different MSV isolates, suggesting that the cellular sequences can be expressed in different positions relative to murine leukemia virus-derived information present in MSV. Deletions in the gag coding region of the different MSVs were consistent with their known gag-related gene products. Based on several features of the hetero-duplex analysis and the known genealogical relationships of the different MSVs, various possible mechanisms for the formation of MSV are considered.", "contents": "Comparative study of different isolates of murine sarcoma virus. The RNA genomes of a variety of murine sarcoma viruses (MSV) were compared by heteroduplex analysis. These viruses included the Moloney-derived isolates 124-MSV, m1-MSV, m3-MSV, HT1-MSV, and NP-MSV and also two independent isolates, Gazdar MSV and 1712-MSV. All of these viral genomes exhibited the acquired cellular sequences previously identified in 3124-MSV and thought to be responsible for transformation and sarcomagenesis. The location of the acquired cellular sequences within the envelope gene was variable in different MSV isolates, suggesting that the cellular sequences can be expressed in different positions relative to murine leukemia virus-derived information present in MSV. Deletions in the gag coding region of the different MSVs were consistent with their known gag-related gene products. Based on several features of the hetero-duplex analysis and the known genealogical relationships of the different MSVs, various possible mechanisms for the formation of MSV are considered."}
{"id": "PMID:229257", "title": "Heteroduplex analysis of the RNA of clone 3 Moloney murine sarcoma virus.", "content": "Heteroduplex analysis of the RNA isolated from purified virions of clone 3 Moloney murine sarcoma virus (M-MSV) hybridized to cDNA's from Moloney murine leukemia virus (M-MLV) and clone 124 M-MSV shows that the main physical component of clone 3 RNA is missing all or most of the 1.5-kilobase (kb) clone 124 M-MSV specific sequence denoted beta s (S. Hu et al. Cell 10:469--477, 1977). This sequence is either deleted in clone 3 RNA or substituted by a very short (0.3-kilobase) sequence. In other respects, clone 3 and clone 124 RNAs show the same heteroduplex structure relative to M-MLV. Since beta s is believed to contain the src gene(s) of clone 124 RNA, this result leaves as an unresolved question the nature of the src gene(s) of the clone 3 M-MSV RNA complex.", "contents": "Heteroduplex analysis of the RNA of clone 3 Moloney murine sarcoma virus. Heteroduplex analysis of the RNA isolated from purified virions of clone 3 Moloney murine sarcoma virus (M-MSV) hybridized to cDNA's from Moloney murine leukemia virus (M-MLV) and clone 124 M-MSV shows that the main physical component of clone 3 RNA is missing all or most of the 1.5-kilobase (kb) clone 124 M-MSV specific sequence denoted beta s (S. Hu et al. Cell 10:469--477, 1977). This sequence is either deleted in clone 3 RNA or substituted by a very short (0.3-kilobase) sequence. In other respects, clone 3 and clone 124 RNAs show the same heteroduplex structure relative to M-MLV. Since beta s is believed to contain the src gene(s) of clone 124 RNA, this result leaves as an unresolved question the nature of the src gene(s) of the clone 3 M-MSV RNA complex."}
{"id": "PMID:229258", "title": "Herpes simplex virus DNA synthesis in a partially purified soluble extract from infected cells.", "content": "HEp-2 cells were infected with herpes simplex virus type 1 and extracted with 0.25% Triton X-100 and 0.1 M NaCl. The extract was sedimented on sucrose gradients, and the fractions containing the endogenous DNA polymerizing activity (replication complex) were collected. The properties of the replication complex were partially characterized. Under optimal conditions 375 pmol of dTMP per micrograms of DNA was incorporated, which corresponds to about 50% replication of preexisting viral DNA. The replication complex was shown to contain only DNA of viral origin by its density in CsCl. By using specific assays for DNA polymerases alpha, beta, gamma, and herpes simplex virus, we found that only the viral DNA polymerase copurified with the replication complex.", "contents": "Herpes simplex virus DNA synthesis in a partially purified soluble extract from infected cells. HEp-2 cells were infected with herpes simplex virus type 1 and extracted with 0.25% Triton X-100 and 0.1 M NaCl. The extract was sedimented on sucrose gradients, and the fractions containing the endogenous DNA polymerizing activity (replication complex) were collected. The properties of the replication complex were partially characterized. Under optimal conditions 375 pmol of dTMP per micrograms of DNA was incorporated, which corresponds to about 50% replication of preexisting viral DNA. The replication complex was shown to contain only DNA of viral origin by its density in CsCl. By using specific assays for DNA polymerases alpha, beta, gamma, and herpes simplex virus, we found that only the viral DNA polymerase copurified with the replication complex."}
{"id": "PMID:229259", "title": "The nonstructural component of the Abelson murine leukemia virus polyprotein P120 is encoded by newly acquired genetic sequences.", "content": "The Abelson leukemia virus (AbLV) polyprotein P120 is compared to translational products representing the entire Moloney murine leukemia virus (MuLV) genome on the basis of [35S]methionine tryptic peptide composition. Three methionine-containing tryptic peptides present in Moloney Pr65gag are each shown to be present in both Pr75gag and in Pr180gag-pol. Of these, one peptide, corresponding to Moloney MuLV p12, but neither of two p30-specific peptides are present in AbLV P120. Among the 12 remaining methionine-containing peptides present in AbLV P120, many, if not all, are unique to AbLV P120 and not shared by either Moloney MuLV Pr180gag-pol or Pr82gag.", "contents": "The nonstructural component of the Abelson murine leukemia virus polyprotein P120 is encoded by newly acquired genetic sequences. The Abelson leukemia virus (AbLV) polyprotein P120 is compared to translational products representing the entire Moloney murine leukemia virus (MuLV) genome on the basis of [35S]methionine tryptic peptide composition. Three methionine-containing tryptic peptides present in Moloney Pr65gag are each shown to be present in both Pr75gag and in Pr180gag-pol. Of these, one peptide, corresponding to Moloney MuLV p12, but neither of two p30-specific peptides are present in AbLV P120. Among the 12 remaining methionine-containing peptides present in AbLV P120, many, if not all, are unique to AbLV P120 and not shared by either Moloney MuLV Pr180gag-pol or Pr82gag."}
{"id": "PMID:229260", "title": "Peptide map comparison of the proteins of infectious bursal disease virus.", "content": "The genome of infectious bursal disease virus consists of two segments of double-stranded RNA of 2.5 X 10(6) and 2.2 X 10(6) molecular weight. Polyacrylamide gel electrophoresis of purified virus resolved four structural polypeptides: VP-1 (90,000), VP-2 (41,000), VP-3 (35,000), and VP-4 (28,000). Peptide map comparisons of radioiodinated virion proteins indicated no precursor-product relationship between them. The possible relationship between the size of the virus genome and the number and sizes of different viral proteins is discussed.", "contents": "Peptide map comparison of the proteins of infectious bursal disease virus. The genome of infectious bursal disease virus consists of two segments of double-stranded RNA of 2.5 X 10(6) and 2.2 X 10(6) molecular weight. Polyacrylamide gel electrophoresis of purified virus resolved four structural polypeptides: VP-1 (90,000), VP-2 (41,000), VP-3 (35,000), and VP-4 (28,000). Peptide map comparisons of radioiodinated virion proteins indicated no precursor-product relationship between them. The possible relationship between the size of the virus genome and the number and sizes of different viral proteins is discussed."}
{"id": "PMID:229261", "title": "Immunochemical characterization of Epstein-Barr virus-associated early and late antigens in n-butyrate-treated P3HR-1 cells.", "content": "Sodium butyrate induces the Epstein-Barr virus cycle in latently infected P3HR-1 cells with a high efficiency. This fact was utilized for the metabolic labeling of the Epstein-Barr virus antigens. Nonproducer Raji cells, lacking both early antigen and viral capsid antigen, were used as controls. Immunoprecipitation patterns were compared with 13 anti-Epstein-Barr virus (viral capsid antigen) - positive and 3 negative sera. Sixteen polypeptides were identified as being associated with the lytic Epstein-Barr virus cycle. Their molecular weights ranged from 31,000 (31K) to 275K on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Two polypeptides, 158K and 165K, could be classified as late viral products on the basis of their sensitivity to cytosine arabinoside. Six of the polypeptides, i.e., 90K, 95K, 134K, 165K, 236K, and 275K, were detected by [(3)H]glucosamine labeling. Among the early, cytosine arabinoside-insensitive polypeptides detected by [(35)S]methionine labeling, a 152K component appears to be a major constituent of early antigen. This polypeptide was precipitated by all anti-Epstein-Barr virus-positive sera tested. As a rule, together with the 103K and 134K polypeptides, the 152K component is precipitated by anti-early antigen, R (restricted) antibodies. In addition, anti-early antigen D (diffuse) antibodies precipitate 31K, 51K, 65K, and 90K components.", "contents": "Immunochemical characterization of Epstein-Barr virus-associated early and late antigens in n-butyrate-treated P3HR-1 cells. Sodium butyrate induces the Epstein-Barr virus cycle in latently infected P3HR-1 cells with a high efficiency. This fact was utilized for the metabolic labeling of the Epstein-Barr virus antigens. Nonproducer Raji cells, lacking both early antigen and viral capsid antigen, were used as controls. Immunoprecipitation patterns were compared with 13 anti-Epstein-Barr virus (viral capsid antigen) - positive and 3 negative sera. Sixteen polypeptides were identified as being associated with the lytic Epstein-Barr virus cycle. Their molecular weights ranged from 31,000 (31K) to 275K on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Two polypeptides, 158K and 165K, could be classified as late viral products on the basis of their sensitivity to cytosine arabinoside. Six of the polypeptides, i.e., 90K, 95K, 134K, 165K, 236K, and 275K, were detected by [(3)H]glucosamine labeling. Among the early, cytosine arabinoside-insensitive polypeptides detected by [(35)S]methionine labeling, a 152K component appears to be a major constituent of early antigen. This polypeptide was precipitated by all anti-Epstein-Barr virus-positive sera tested. As a rule, together with the 103K and 134K polypeptides, the 152K component is precipitated by anti-early antigen, R (restricted) antibodies. In addition, anti-early antigen D (diffuse) antibodies precipitate 31K, 51K, 65K, and 90K components."}
{"id": "PMID:229262", "title": "Alterations in glycosphingolipid patterns in a line of African green monkey kidney cells infected with herpesvirus.", "content": "The major glycosphingolipids (GSLs) of a line of African green monkey kidney cells (BGM) were characterized as glucosylceramide, lactosylceramide, galactosyl-galactosyl-glucosylceramide, and N-acetylgalactosaminyl-galactosyl-galactosyl-glucosylceramide. Neutral GSLs accounted for approximately 80% of the total GSLs isolated. The predominant gangliosides were N-acetylneuraminyl-galactosyl-glucosylceramide, N-acetylgalactosaminyl-N-acetylneuraminyl-galactosyl- glucosylceramide, and galactosyl-N-acetylgalactosaminyl-N-acetylneuraminyl -galactosyl-glucosylceramide. The incorporation of labeled galactose into GSLs was compared in mock-infected and herpes simplex virus type 1-infected BGM cells. Herpes simplex virus type 1 infection resulted in a three- to four-fold increase in galactose incorporation into glucosylceramide and a decrease in galactose incorporation into galactosyl-galactosyl-glucosylceramide and N-acetyl-galactosaminyl-galactosyl-galactosyl-glucosylceramide. The virus-induced alteration in the GSL labeling pattern occurred early in infection, before the release of infectious virus, and was not prevented by the presence of cytosine arabinoside. Treatment of uninfected BGM cells with cycloheximide resulted in alterations in the GSL pattern which were similar to those observed in herpes simplex virus type 1-infected cells. These observations suggest that an early virus function such as inhibition of host cell protein synthesis is responsible for the observed alterations of GSL metabolism. Experiments with a syncytium-producing strain of herpes simplex virus type 1, herpes simplex virus type 2, and pseudorabies virus indicated that other herpes viruses altered GSL metabolism in a manner similar to herpes simplex virus type 1.", "contents": "Alterations in glycosphingolipid patterns in a line of African green monkey kidney cells infected with herpesvirus. The major glycosphingolipids (GSLs) of a line of African green monkey kidney cells (BGM) were characterized as glucosylceramide, lactosylceramide, galactosyl-galactosyl-glucosylceramide, and N-acetylgalactosaminyl-galactosyl-galactosyl-glucosylceramide. Neutral GSLs accounted for approximately 80% of the total GSLs isolated. The predominant gangliosides were N-acetylneuraminyl-galactosyl-glucosylceramide, N-acetylgalactosaminyl-N-acetylneuraminyl-galactosyl- glucosylceramide, and galactosyl-N-acetylgalactosaminyl-N-acetylneuraminyl -galactosyl-glucosylceramide. The incorporation of labeled galactose into GSLs was compared in mock-infected and herpes simplex virus type 1-infected BGM cells. Herpes simplex virus type 1 infection resulted in a three- to four-fold increase in galactose incorporation into glucosylceramide and a decrease in galactose incorporation into galactosyl-galactosyl-glucosylceramide and N-acetyl-galactosaminyl-galactosyl-galactosyl-glucosylceramide. The virus-induced alteration in the GSL labeling pattern occurred early in infection, before the release of infectious virus, and was not prevented by the presence of cytosine arabinoside. Treatment of uninfected BGM cells with cycloheximide resulted in alterations in the GSL pattern which were similar to those observed in herpes simplex virus type 1-infected cells. These observations suggest that an early virus function such as inhibition of host cell protein synthesis is responsible for the observed alterations of GSL metabolism. Experiments with a syncytium-producing strain of herpes simplex virus type 1, herpes simplex virus type 2, and pseudorabies virus indicated that other herpes viruses altered GSL metabolism in a manner similar to herpes simplex virus type 1."}
{"id": "PMID:229263", "title": "Herpes simplex virus glycoproteins: participation of individual herpes simplex virus type 1 glycoprotein antigens in immunocytolysis and their correlation with previously identified glycopolypeptides.", "content": "Tissue culture cells infected with herpes simplex type 1 virus express virus-specified glycoprotein antigens on the plasma membrane. Three of these have been previously identified and have been designated as Ag-11, Ag-8, and Ag-6. In the present study, immunoglobulins to each of the antigens were shown to be capable of mediating immunocytolysis in the presence of either complement (antibody-dependent complement-mediated cytotoxicity) or peripheral blood mononuclear cells (antibody-dependent cell-mediated cytotoxicity [ADCC]). Two herpes simplex virus type 1 strains, VR-3 and F, reacted similarly in the ADCC test in the presence of immunoglobulins to Ag-11, Ag-8, and Ag-6 in both infected Chang liver cells and HEp-2 cells. Anti-Ag-6, however, produced a lower ADCC reaction in HEp-2 cells than in Chang liver cells, suggesting differences in the Ag-6 surface expression in, or release from, these cells. Chang liver and HEp-2 cells infected with the MP mutant strain of herpes simplex virus type 1 showed reduced ADCC in the presence of anti-Ag-11 and anti-Ag-8, but no reactivity at all with anti-Ag-6. Crossed immunoelectrophoretic analysis showed that MP-infected cell extracts contain Ag-11 and Ag-8, but lack Ag-6. Polypeptide analysis of herpes simplex virus type 1 strains F, VR-3, and MP showed that Ag-11 consists of the glycoproteins gA and gB, that Ag-8 consists of gD, and that Ag-6 consists of gC. In conclusion, the present study demonstrates that either one of the glycoproteins (gC, gD, and a mixture of gA and gB) can function as a target for immunocytolysis and that the antibody preparation to gC (Ag-6) does not cross-react with any of the other glycoproteins.", "contents": "Herpes simplex virus glycoproteins: participation of individual herpes simplex virus type 1 glycoprotein antigens in immunocytolysis and their correlation with previously identified glycopolypeptides. Tissue culture cells infected with herpes simplex type 1 virus express virus-specified glycoprotein antigens on the plasma membrane. Three of these have been previously identified and have been designated as Ag-11, Ag-8, and Ag-6. In the present study, immunoglobulins to each of the antigens were shown to be capable of mediating immunocytolysis in the presence of either complement (antibody-dependent complement-mediated cytotoxicity) or peripheral blood mononuclear cells (antibody-dependent cell-mediated cytotoxicity [ADCC]). Two herpes simplex virus type 1 strains, VR-3 and F, reacted similarly in the ADCC test in the presence of immunoglobulins to Ag-11, Ag-8, and Ag-6 in both infected Chang liver cells and HEp-2 cells. Anti-Ag-6, however, produced a lower ADCC reaction in HEp-2 cells than in Chang liver cells, suggesting differences in the Ag-6 surface expression in, or release from, these cells. Chang liver and HEp-2 cells infected with the MP mutant strain of herpes simplex virus type 1 showed reduced ADCC in the presence of anti-Ag-11 and anti-Ag-8, but no reactivity at all with anti-Ag-6. Crossed immunoelectrophoretic analysis showed that MP-infected cell extracts contain Ag-11 and Ag-8, but lack Ag-6. Polypeptide analysis of herpes simplex virus type 1 strains F, VR-3, and MP showed that Ag-11 consists of the glycoproteins gA and gB, that Ag-8 consists of gD, and that Ag-6 consists of gC. In conclusion, the present study demonstrates that either one of the glycoproteins (gC, gD, and a mixture of gA and gB) can function as a target for immunocytolysis and that the antibody preparation to gC (Ag-6) does not cross-react with any of the other glycoproteins."}
{"id": "PMID:229264", "title": "gag-Related polypeptides encoded by replication-defective avian oncoviruses.", "content": "The content of viral structural (gag) protein sequences in polypeptides encoded by replication-defective avian erythroblastosis virus (AEV) and myelocytomatosis virus MC29 was assessed by immunological and peptide analyses. Direct comparison with gag proteins of the associated helper viruses revealed that MC29 110K polypeptide contained p19, p12, and p27, whereas the AEV 75K polypeptide had sequences related only to p19 and p12. Both of these polypeptides contained some information that was unrelated to gag, pol, or env gene products. In addition, no homology was detected between these unique peptides of MC29 110K and AEV 75K. The AEV 75K polypeptide shared strain-specific tryptic peptides with the p19 encoded by its naturally occurring helper virus; this observation suggests that gag-related sequences in 75K were originally derived from the helper viral gag gene. Digestion of oxidized MC29 110K and AEV 75K proteins with the Staphylococcus aureus V8 protease generated a fragment which comigrated with N-acetylmethionylsulfoneglutamic acid, a blocked dipeptide which is the putative amino-terminal sequence of structural protein p19 and gag precursor Pr76gag. This last finding is evidence that the gag sequences are located at the N-terminal end of the MC29 110K and AEV 75K polypeptides.", "contents": "gag-Related polypeptides encoded by replication-defective avian oncoviruses. The content of viral structural (gag) protein sequences in polypeptides encoded by replication-defective avian erythroblastosis virus (AEV) and myelocytomatosis virus MC29 was assessed by immunological and peptide analyses. Direct comparison with gag proteins of the associated helper viruses revealed that MC29 110K polypeptide contained p19, p12, and p27, whereas the AEV 75K polypeptide had sequences related only to p19 and p12. Both of these polypeptides contained some information that was unrelated to gag, pol, or env gene products. In addition, no homology was detected between these unique peptides of MC29 110K and AEV 75K. The AEV 75K polypeptide shared strain-specific tryptic peptides with the p19 encoded by its naturally occurring helper virus; this observation suggests that gag-related sequences in 75K were originally derived from the helper viral gag gene. Digestion of oxidized MC29 110K and AEV 75K proteins with the Staphylococcus aureus V8 protease generated a fragment which comigrated with N-acetylmethionylsulfoneglutamic acid, a blocked dipeptide which is the putative amino-terminal sequence of structural protein p19 and gag precursor Pr76gag. This last finding is evidence that the gag sequences are located at the N-terminal end of the MC29 110K and AEV 75K polypeptides."}
{"id": "PMID:229265", "title": "Analysis of cellular integration sites in avian sarcoma virus infected duck embryo cells.", "content": "The cellular sites of integration of avian sarcoma virus (ASV) have been examined in clones of duck embryo cells infected with the Bratislava 77 strain of ASV using restriction endonuclease digestion, agarose gel electrophoresis, Southern blotting, and hybridization with labeled ASV complementary DNA probes. DNA prepared from 11 clones of duck embryo cells infected with the Bratislava 77 strain of ASV was digested with the restriction enzymes HpaI, which cleaves once within the viral genome, and Hind III, which cleaves twice within the viral genome, and the virus-cell DNA juncture fragments were resolved by agarose gel electrophoresis. Analysis of the virus-cell junctures present in individual ASV-infected duck embryo clones revealed that all clones contain at least one copy of nondefective proviral DNA with some clones containing as many as 5 to 6 copies of proviral DNA. A comparison of the virus-cell juncture fragments present in different ASV-infected clones showed that each clone contains a unique set of virus-cell junctures. These data suggest that ASV DNA can integrate at multiple sites within the duck embryo cell genome and that these sites appear to be different as defined by digestion with the restriction enzymes HpaI and HindIII.", "contents": "Analysis of cellular integration sites in avian sarcoma virus infected duck embryo cells. The cellular sites of integration of avian sarcoma virus (ASV) have been examined in clones of duck embryo cells infected with the Bratislava 77 strain of ASV using restriction endonuclease digestion, agarose gel electrophoresis, Southern blotting, and hybridization with labeled ASV complementary DNA probes. DNA prepared from 11 clones of duck embryo cells infected with the Bratislava 77 strain of ASV was digested with the restriction enzymes HpaI, which cleaves once within the viral genome, and Hind III, which cleaves twice within the viral genome, and the virus-cell DNA juncture fragments were resolved by agarose gel electrophoresis. Analysis of the virus-cell junctures present in individual ASV-infected duck embryo clones revealed that all clones contain at least one copy of nondefective proviral DNA with some clones containing as many as 5 to 6 copies of proviral DNA. A comparison of the virus-cell juncture fragments present in different ASV-infected clones showed that each clone contains a unique set of virus-cell junctures. These data suggest that ASV DNA can integrate at multiple sites within the duck embryo cell genome and that these sites appear to be different as defined by digestion with the restriction enzymes HpaI and HindIII."}
{"id": "PMID:229266", "title": "Protease required for processing picornaviral coat protein resides in the viral replicase gene.", "content": "Partial purification of the encephalomyocarditis protease synthesized in extracts from rabbit reticulocytes shows that the activity responsible for cleaving coat precursor protein cosediments with a previously unmapped virus-coded protein with an apparent molecular weight of 20,000. Tryptic analysis shows that this protein is derived from protein D, a virus-coded component of the encephalomyocarditis RNA polymerase.", "contents": "Protease required for processing picornaviral coat protein resides in the viral replicase gene. Partial purification of the encephalomyocarditis protease synthesized in extracts from rabbit reticulocytes shows that the activity responsible for cleaving coat precursor protein cosediments with a previously unmapped virus-coded protein with an apparent molecular weight of 20,000. Tryptic analysis shows that this protein is derived from protein D, a virus-coded component of the encephalomyocarditis RNA polymerase."}
{"id": "PMID:229267", "title": "Membrane proteins specified by herpes simplex viruses. V. Identification of an Fc-binding glycoprotein.", "content": "A glycoprotein with affinity for the Fc region of immunoglobulin was isolated from extracts of cultured cells infected with herpes simplex virus type 1, and experiments were done to characterize its properties and to investigate whether it could account for the Fc-binding activity previously demonstrated on the surfaces of intact herpes simplex virus-infected cells. The technique of affinity chromatography was used to identify and isolate the Fc-binding glycoprotein and to demonstrate the specificity of its interaction with immunoglobulin G-Fc. Although three electrophoretically distinguishable Fc-binding polypeptides were identified by affinity chromatography, these three species appear to be different forms of the same translation product, based on comparisons of proteolytic digestion products and on the kinetics of appearance of each form after a brief pulse with radioactive amino acids. The results suggest that one polypeptide, designated pE, is processed to yield gE1, which is in turn processed to yield gE2. Both gE1 and gE2 are glycosylated membrane proteins and both can be labeled by the lactoperoxidase-catalyzed radioiodination of intact infected cells, indicating the presence of these proteins in surface membranes of the cells. Increases in the amounts of gE1 and gE2 at the cell surface were found to parallel the increase in Fc-binding activity of intact infected cells.", "contents": "Membrane proteins specified by herpes simplex viruses. V. Identification of an Fc-binding glycoprotein. A glycoprotein with affinity for the Fc region of immunoglobulin was isolated from extracts of cultured cells infected with herpes simplex virus type 1, and experiments were done to characterize its properties and to investigate whether it could account for the Fc-binding activity previously demonstrated on the surfaces of intact herpes simplex virus-infected cells. The technique of affinity chromatography was used to identify and isolate the Fc-binding glycoprotein and to demonstrate the specificity of its interaction with immunoglobulin G-Fc. Although three electrophoretically distinguishable Fc-binding polypeptides were identified by affinity chromatography, these three species appear to be different forms of the same translation product, based on comparisons of proteolytic digestion products and on the kinetics of appearance of each form after a brief pulse with radioactive amino acids. The results suggest that one polypeptide, designated pE, is processed to yield gE1, which is in turn processed to yield gE2. Both gE1 and gE2 are glycosylated membrane proteins and both can be labeled by the lactoperoxidase-catalyzed radioiodination of intact infected cells, indicating the presence of these proteins in surface membranes of the cells. Increases in the amounts of gE1 and gE2 at the cell surface were found to parallel the increase in Fc-binding activity of intact infected cells."}
{"id": "PMID:229268", "title": "Analysis of the DNAs from seven varicella-zoster virus isolates.", "content": "The 32P-labeled DNAs from seven different clinical isolates of human varicella-zoster virus (VZV) were independently digested with five site-specific restriction endonucleases, EcoRI, HindIII, SmaI, BamHI, and AvaI. The digestion products were analyzed by electrophoresis on 0.5% agarose gels followed by autoradiography of the dried gels. Evaluation of the restriction enzyme cleavage patterns revealed small variations among the VZV DNAs. The VZV DNAs were also compared based on their buoyant densities in CsCl. No significant buoyant density differences were detected among the VZV DNAs.", "contents": "Analysis of the DNAs from seven varicella-zoster virus isolates. The 32P-labeled DNAs from seven different clinical isolates of human varicella-zoster virus (VZV) were independently digested with five site-specific restriction endonucleases, EcoRI, HindIII, SmaI, BamHI, and AvaI. The digestion products were analyzed by electrophoresis on 0.5% agarose gels followed by autoradiography of the dried gels. Evaluation of the restriction enzyme cleavage patterns revealed small variations among the VZV DNAs. The VZV DNAs were also compared based on their buoyant densities in CsCl. No significant buoyant density differences were detected among the VZV DNAs."}
{"id": "PMID:229269", "title": "Inactivation of influenza and vesicular stomatitis virion RNA polymerase activities by photoreaction with 4'-substituted psoralens.", "content": "Irradiation of purified influenza virus and vesicular stomatitis virus (VSV) with long-wavelength UV light in the presence of 4'-substituted psoralens inactivated the virion-associated RNA polymerase activity. Inactivation was apparently due to psoralen modification of the viral genome RNAs, since cations that decrease psoralen binding to nucleic acids had a protective effect, and reconstitution of VSV RNA polymerase activity was inhibited by photoreaction of nucleoprotein cores but not by pretreatment of soluble fraction from dissociated virions. Partially inactivated viral particles synthesized reduced amounts of full-length RNA products in vitro without an increase in prematurely terminated transcripts. VSV leader RNA formation was relatively resistant to psoralen photoinactivation, and sequential transcription was maintained by photoreacted VSV. The all-or-none psoralen effect on virion-associated RNA polymerase activities may be due to a differential photosensitivity of promoter sites or to structural changes in modified viral genome RNAs that prevent formation of new mRNA chains.", "contents": "Inactivation of influenza and vesicular stomatitis virion RNA polymerase activities by photoreaction with 4'-substituted psoralens. Irradiation of purified influenza virus and vesicular stomatitis virus (VSV) with long-wavelength UV light in the presence of 4'-substituted psoralens inactivated the virion-associated RNA polymerase activity. Inactivation was apparently due to psoralen modification of the viral genome RNAs, since cations that decrease psoralen binding to nucleic acids had a protective effect, and reconstitution of VSV RNA polymerase activity was inhibited by photoreaction of nucleoprotein cores but not by pretreatment of soluble fraction from dissociated virions. Partially inactivated viral particles synthesized reduced amounts of full-length RNA products in vitro without an increase in prematurely terminated transcripts. VSV leader RNA formation was relatively resistant to psoralen photoinactivation, and sequential transcription was maintained by photoreacted VSV. The all-or-none psoralen effect on virion-associated RNA polymerase activities may be due to a differential photosensitivity of promoter sites or to structural changes in modified viral genome RNAs that prevent formation of new mRNA chains."}
{"id": "PMID:229270", "title": "Restriction endonuclease mapping of unintegrated proviral DNA of Snyder-Theilen feline sarcoma virus: localization of sarcoma-specific sequences.", "content": "Extrachromosomal DNA purified from mink cells acutely infected with the Snyder-Theilen strain of feline sarcoma virus (FeSV) was digested with restriction endonucleases, and the DNA fragments were electrophoretically separated, transferred to a solid substrate, and hybridized with radiolabeled DNA transcripts complementary to different portions of the FeSV RNA genome. Major DNA species 8.4 and 5.0 kilobase pairs (kbp) long represent the linear, unintegrated proviruses of Snyder-Theilen feline leukemia virus and FeSV, respectively. Transfection experiments performed with electroeluted DNAs showed that the 8.4-kbp form led to the production of replicating nontransforming virus in mink and cat cells; in contrast, the 5.0-kbp DNA produced helper virus-independent foci of transformation in mouse NIH/3T3 cells and helper virus-dependent foci in mink cells at an efficiency comparable to that obtained with unfractionated extrachromosomal DNA. Sites of restriction endonuclease cleavage for six enzymes were oriented with respect to one another within the FeSV provirus. EcoRI recognized cleavage sites at 0.3 to 0.4 kbp from each terminus of FeSV DNA, reducing the 5.0-kbp DNA to molecules 4.3 kbp long; this enzyme excised a large internal proviral DNA fragment of corresponding size from the DNA of FeSV-transformed mink nonproducer cells. By using DNA transcripts complementary to different portions of the FeSV genome, sarcoma-specific sequences (the FeSV src gene) were positioned within 2.1 and 3.4 kbp from the 5' end of the proviral DNA with respect to the viral RNA genome. The src gene is flanked at both ends by sequences shared in common with feline leukemia virus. The localization of src sequences to this region suggests that a portion of an FeSV polyprotein which contains feline oncornavirus-associated cell membrane antigen (FOCMA-S) is the major product of this gene.", "contents": "Restriction endonuclease mapping of unintegrated proviral DNA of Snyder-Theilen feline sarcoma virus: localization of sarcoma-specific sequences. Extrachromosomal DNA purified from mink cells acutely infected with the Snyder-Theilen strain of feline sarcoma virus (FeSV) was digested with restriction endonucleases, and the DNA fragments were electrophoretically separated, transferred to a solid substrate, and hybridized with radiolabeled DNA transcripts complementary to different portions of the FeSV RNA genome. Major DNA species 8.4 and 5.0 kilobase pairs (kbp) long represent the linear, unintegrated proviruses of Snyder-Theilen feline leukemia virus and FeSV, respectively. Transfection experiments performed with electroeluted DNAs showed that the 8.4-kbp form led to the production of replicating nontransforming virus in mink and cat cells; in contrast, the 5.0-kbp DNA produced helper virus-independent foci of transformation in mouse NIH/3T3 cells and helper virus-dependent foci in mink cells at an efficiency comparable to that obtained with unfractionated extrachromosomal DNA. Sites of restriction endonuclease cleavage for six enzymes were oriented with respect to one another within the FeSV provirus. EcoRI recognized cleavage sites at 0.3 to 0.4 kbp from each terminus of FeSV DNA, reducing the 5.0-kbp DNA to molecules 4.3 kbp long; this enzyme excised a large internal proviral DNA fragment of corresponding size from the DNA of FeSV-transformed mink nonproducer cells. By using DNA transcripts complementary to different portions of the FeSV genome, sarcoma-specific sequences (the FeSV src gene) were positioned within 2.1 and 3.4 kbp from the 5' end of the proviral DNA with respect to the viral RNA genome. The src gene is flanked at both ends by sequences shared in common with feline leukemia virus. The localization of src sequences to this region suggests that a portion of an FeSV polyprotein which contains feline oncornavirus-associated cell membrane antigen (FOCMA-S) is the major product of this gene."}
{"id": "PMID:229271", "title": "UV inactivation of the biological activity of defective interfering particles generated by vesicular stomatitis virus.", "content": "UV inactivation of vesicular stomatitis virus and its defective interfering (DI) particles was measured in order to obtain the target size for interference. In the case of DI particles whose genomes mapped at the 5' end of the virion RNA, this target size corresponded to the entire DI particle RNA molecule regardless of whether it amounted to 10, 30, or 50% of the viral genome. These data were interpreted as demonstrating that both termini of the DI particle RNAs were required for their replication and for interference with virion RNA replication. The unique heat-resistant DI particle, with an RNA molecule corresponding to the 3' half of the viral genome, exhibited an inactivation target size of approximately 42% of its RNA molecule with respect to both homotypic and heterotypic interference. Unlike other DI particles, this particle interfered with virion primary transcription. The unusual inactivation target size of the heat-resistant DI particle was interpreted as being a compromise between the requirements for replication of its genome and those for interference with virion primary transcription.", "contents": "UV inactivation of the biological activity of defective interfering particles generated by vesicular stomatitis virus. UV inactivation of vesicular stomatitis virus and its defective interfering (DI) particles was measured in order to obtain the target size for interference. In the case of DI particles whose genomes mapped at the 5' end of the virion RNA, this target size corresponded to the entire DI particle RNA molecule regardless of whether it amounted to 10, 30, or 50% of the viral genome. These data were interpreted as demonstrating that both termini of the DI particle RNAs were required for their replication and for interference with virion RNA replication. The unique heat-resistant DI particle, with an RNA molecule corresponding to the 3' half of the viral genome, exhibited an inactivation target size of approximately 42% of its RNA molecule with respect to both homotypic and heterotypic interference. Unlike other DI particles, this particle interfered with virion primary transcription. The unusual inactivation target size of the heat-resistant DI particle was interpreted as being a compromise between the requirements for replication of its genome and those for interference with virion primary transcription."}
{"id": "PMID:229272", "title": "Conserved region of mammalian retrovirus RNA.", "content": "The viral RNAs of various mammalian retroviruses contain highly conserved sequences close to their 3' ends. This was demonstrated by interviral molecular hybridization between fractionated viral complementary DNA (cDNA) and RNA. cDNA near the 3' end (cDNA(3')) from a rat virus (RPL strain) was fractionated by size and mixed with mouse virus RNA (Rauscher leukemia virus). No hybridization occurred with total cDNA (cDNA(total)), in agreement with previous results, but a cross-reacting sequence was found with the fractionated cDNA(3'). The sequences between 50 to 400 nucleotides from the 3' terminus of heteropolymeric RNA were most hybridizable. The rat viral cDNA(3') hybridized with mouse virus RNA more extensively than with RNA of remotely related retroviruses. The related viral sequence of the rodent viruses (mouse and rat) showed as much divergence in heteroduplex thermal denaturation profiles as did the unique sequence DNA of these two rodents. This suggests that over a period of time, rodent viruses have preserved a sequence with changes correlated to phylogenetic distance of hosts. The cross-reacting sequence of replication-competent retroviruses was conserved even in the genome of the replication-defective sarcoma virus and was also located in these genomes near the 3' end of 30S RNA. A fraction of RD114 cDNA(3'), corresponding to the conserved region, cross-hybridized extensively with RNA of a baboon endogenous virus (M7). Fractions of similar size prepared from cDNA(3') of MPMV, a primate type D virus, hybridized with M7 RNA to a lesser extent. Hybridization was not observed between Mason-Pfizer monkey virus and M7 if total cDNA's were incubated with viral RNAs. The degree of cross-reaction of the shared sequence appeared to be influenced by viral ancestral relatedness and host cell phylogenetic relationships. Thus, the strikingly high extent of cross-reaction at the conserved region between rodent viruses and simian sarcoma virus and between baboon virus and RD114 virus may reflect ancestral relatedness of the viruses. Slight cross-reaction at the site between type B and C viruses of rodents (mouse mammary tumor virus and RPL virus, 58-2T) or type C and D viruses of primates (M7, RD114, and Mason-Pfizer monkey virus) may have arisen at the conserved region through a mechanism that depends more on the phylogenetic relatedness of the host cells than on the viral type or origin. Determining the sequence of the conserved region may help elucidate this mechanism. The conserved sequences in retroviruses described here may be an important functional unit for the life cycle of many retroviruses.", "contents": "Conserved region of mammalian retrovirus RNA. The viral RNAs of various mammalian retroviruses contain highly conserved sequences close to their 3' ends. This was demonstrated by interviral molecular hybridization between fractionated viral complementary DNA (cDNA) and RNA. cDNA near the 3' end (cDNA(3')) from a rat virus (RPL strain) was fractionated by size and mixed with mouse virus RNA (Rauscher leukemia virus). No hybridization occurred with total cDNA (cDNA(total)), in agreement with previous results, but a cross-reacting sequence was found with the fractionated cDNA(3'). The sequences between 50 to 400 nucleotides from the 3' terminus of heteropolymeric RNA were most hybridizable. The rat viral cDNA(3') hybridized with mouse virus RNA more extensively than with RNA of remotely related retroviruses. The related viral sequence of the rodent viruses (mouse and rat) showed as much divergence in heteroduplex thermal denaturation profiles as did the unique sequence DNA of these two rodents. This suggests that over a period of time, rodent viruses have preserved a sequence with changes correlated to phylogenetic distance of hosts. The cross-reacting sequence of replication-competent retroviruses was conserved even in the genome of the replication-defective sarcoma virus and was also located in these genomes near the 3' end of 30S RNA. A fraction of RD114 cDNA(3'), corresponding to the conserved region, cross-hybridized extensively with RNA of a baboon endogenous virus (M7). Fractions of similar size prepared from cDNA(3') of MPMV, a primate type D virus, hybridized with M7 RNA to a lesser extent. Hybridization was not observed between Mason-Pfizer monkey virus and M7 if total cDNA's were incubated with viral RNAs. The degree of cross-reaction of the shared sequence appeared to be influenced by viral ancestral relatedness and host cell phylogenetic relationships. Thus, the strikingly high extent of cross-reaction at the conserved region between rodent viruses and simian sarcoma virus and between baboon virus and RD114 virus may reflect ancestral relatedness of the viruses. Slight cross-reaction at the site between type B and C viruses of rodents (mouse mammary tumor virus and RPL virus, 58-2T) or type C and D viruses of primates (M7, RD114, and Mason-Pfizer monkey virus) may have arisen at the conserved region through a mechanism that depends more on the phylogenetic relatedness of the host cells than on the viral type or origin. Determining the sequence of the conserved region may help elucidate this mechanism. The conserved sequences in retroviruses described here may be an important functional unit for the life cycle of many retroviruses."}
{"id": "PMID:229273", "title": "Viable deletion mutant of human papovavirus BK that induces insulinomas in hamsters.", "content": "A plaque morphology mutant (pm-522) of human papovavirus BK, which was rescued from a human papovavirus BK-induced hamster pineocytoma, was characterized and compared with a cloned wild-type virus (wt-501). Mutant pm-522 formed turbid plaques and grew more slowly than wt-501 in human embryonic kidney (HEK) cells. The immunofluorescence assay revealed that more HEK cells underwent abortive infection with pm-522 than with wt-501. Whereas wt-501 induced brain tumors and osteosarcomas, but no insulinomas, in hamsters, pm-522 induced brain tumors and insulinomas. The DNA of pm-522 was found by electrophoresis and electron microscopy to have a deletion (85 +/- 15 base pairs) and an insertion (40 +/- 10 base pairs) between map coordinates 0.708 and 0.725 from the endonuclease EcoRI cleavage site. These results demonstrate the presence of a viable deletion human papovarivus BK mutant capable of inducing insulinomas in hamsters.", "contents": "Viable deletion mutant of human papovavirus BK that induces insulinomas in hamsters. A plaque morphology mutant (pm-522) of human papovavirus BK, which was rescued from a human papovavirus BK-induced hamster pineocytoma, was characterized and compared with a cloned wild-type virus (wt-501). Mutant pm-522 formed turbid plaques and grew more slowly than wt-501 in human embryonic kidney (HEK) cells. The immunofluorescence assay revealed that more HEK cells underwent abortive infection with pm-522 than with wt-501. Whereas wt-501 induced brain tumors and osteosarcomas, but no insulinomas, in hamsters, pm-522 induced brain tumors and insulinomas. The DNA of pm-522 was found by electrophoresis and electron microscopy to have a deletion (85 +/- 15 base pairs) and an insertion (40 +/- 10 base pairs) between map coordinates 0.708 and 0.725 from the endonuclease EcoRI cleavage site. These results demonstrate the presence of a viable deletion human papovarivus BK mutant capable of inducing insulinomas in hamsters."}
{"id": "PMID:229274", "title": "Simian virus 40 small t antigen is not required for the maintenance of transformation but may act as a promoter (cocarcinogen) during establishment of transformation in resting rat cells.", "content": "Simian virus 40 deletion mutants affecting the 20,000-dalton (20K) t antigen and tsA mutants rendering the 90K T antigen temperature sensitive, as well as double mutants containing both mutations, induced host DNA synthesis in resting rat cells at the restrictive temperature. Nonetheless, the deletion mutants and double mutants did not induce transformation in resting cells even at the permissive temperature. On the other hand, the deletion mutants did induce full transformants when actively growing rat cells were infected; the transformants grew efficiently in agar and to high saturation densities on platic. The double mutants did not induce T-antigen-independent (temperature-insensitive) transformants which were shown previously to arise preferentially from resting cells. Thus, small t antigen was dispensable for the maintenance of the transformed phenotype in T-antigen-dependent rat transformants (transformants derived from growing cells) and may play a role in the establishment of T-antigen-independent transformants. We attempt to establish a parallel between transformation induced by chemical carcinogens and simian virus 40-induced transformation.", "contents": "Simian virus 40 small t antigen is not required for the maintenance of transformation but may act as a promoter (cocarcinogen) during establishment of transformation in resting rat cells. Simian virus 40 deletion mutants affecting the 20,000-dalton (20K) t antigen and tsA mutants rendering the 90K T antigen temperature sensitive, as well as double mutants containing both mutations, induced host DNA synthesis in resting rat cells at the restrictive temperature. Nonetheless, the deletion mutants and double mutants did not induce transformation in resting cells even at the permissive temperature. On the other hand, the deletion mutants did induce full transformants when actively growing rat cells were infected; the transformants grew efficiently in agar and to high saturation densities on platic. The double mutants did not induce T-antigen-independent (temperature-insensitive) transformants which were shown previously to arise preferentially from resting cells. Thus, small t antigen was dispensable for the maintenance of the transformed phenotype in T-antigen-dependent rat transformants (transformants derived from growing cells) and may play a role in the establishment of T-antigen-independent transformants. We attempt to establish a parallel between transformation induced by chemical carcinogens and simian virus 40-induced transformation."}
{"id": "PMID:229275", "title": "Retransformation of a simian virus 40 revertant cell line, which is resistant to viral and DNA infections, by microinjection of viral DNA.", "content": "We have isolated morphological transformants of cultured cells as dense foci on a monolayer of normal cells appproximately 4 weeks after microinjection of purified simian virus 40 DNA (200 to 400 molecules per cell) directly into the nucleus. Both Rat 1 (an established contact-inhibited rat embryo fibroblast line) and F1' 1--4 (a 5-fluorodeoxyuridine-selected flat revertant from the simian virus 40-transformed 14B cell line) were transformed with an efficiency of 5 to 10% of the cells injected. F1' 1--4 is not susceptible to retransformation by either viral or DNA infection (by calcium phosphate-facilitated cellular uptake), and as a result it had previously been thought to possess a host mutation preventing expression of the simian virus 40 genome.", "contents": "Retransformation of a simian virus 40 revertant cell line, which is resistant to viral and DNA infections, by microinjection of viral DNA. We have isolated morphological transformants of cultured cells as dense foci on a monolayer of normal cells appproximately 4 weeks after microinjection of purified simian virus 40 DNA (200 to 400 molecules per cell) directly into the nucleus. Both Rat 1 (an established contact-inhibited rat embryo fibroblast line) and F1' 1--4 (a 5-fluorodeoxyuridine-selected flat revertant from the simian virus 40-transformed 14B cell line) were transformed with an efficiency of 5 to 10% of the cells injected. F1' 1--4 is not susceptible to retransformation by either viral or DNA infection (by calcium phosphate-facilitated cellular uptake), and as a result it had previously been thought to possess a host mutation preventing expression of the simian virus 40 genome."}
{"id": "PMID:229276", "title": "Wilms tumor, misdiagnosed preoperatively: a review of 19 National Wilms Tumor Study I cases.", "content": "This study establishes the difficulty in making specific diagnoses in children with retroperitoneal tumors when only excretory urograms are used in diagnosis. Complementary use of excretory urography and ultrasonography should make the number of preoperative errors less by separating cases of Wilms tumor from those with cystic disease. This investigation underscores the hazards inherent in the use of preoperative irradiation and chemotherapy, since some children with benign disease are likely to receive inappropriate therapy.", "contents": "Wilms tumor, misdiagnosed preoperatively: a review of 19 National Wilms Tumor Study I cases. This study establishes the difficulty in making specific diagnoses in children with retroperitoneal tumors when only excretory urograms are used in diagnosis. Complementary use of excretory urography and ultrasonography should make the number of preoperative errors less by separating cases of Wilms tumor from those with cystic disease. This investigation underscores the hazards inherent in the use of preoperative irradiation and chemotherapy, since some children with benign disease are likely to receive inappropriate therapy."}
{"id": "PMID:229277", "title": "Renal transplantation for Wilms tumor: report of 20 cases.", "content": "Renal transplantation as part of the treatment for Wilms tumor was done on 20 patients. In 80 per cent the neoplasms were bilateral. Transplantation is indicated in individuals whose renal function is severely impaired or absent because of the malignancy, treatment or both. Patients who received homografts less than a year after treatment of the tumors had a 47 per cent incidence of recurrence or metastases compared to a zero incidence of these problems in those whose transplants were delayed for longer periods. Survival for 2 years or more was obtained in 75 per cent of the recipients with unilateral neoplasms and in 38 per cent of the patients with bilateral tumors.", "contents": "Renal transplantation for Wilms tumor: report of 20 cases. Renal transplantation as part of the treatment for Wilms tumor was done on 20 patients. In 80 per cent the neoplasms were bilateral. Transplantation is indicated in individuals whose renal function is severely impaired or absent because of the malignancy, treatment or both. Patients who received homografts less than a year after treatment of the tumors had a 47 per cent incidence of recurrence or metastases compared to a zero incidence of these problems in those whose transplants were delayed for longer periods. Survival for 2 years or more was obtained in 75 per cent of the recipients with unilateral neoplasms and in 38 per cent of the patients with bilateral tumors."}
{"id": "PMID:229291", "title": "Properties of human epithelioid cells established in vitro by a herpesvirus [IBRV(HMC)] isolated from cytomegalovirus-transformed human cells.", "content": "Infectious bovine rhinotracheitis virus [IBRV(HMC)], a double-enveloped herpesvirus, was isolated from human embryo lung fibroblasts transformed by cytomegalovirus (CMV). This agent was identified as an IBRV strain that was antigenically related to human CMV. Inoculation of a primary human kidney cancer cell culture with IBRV(HMC) resulted in persistent infection and subsequent establishment of a cell line [IBRV(HMC)HKC-1]. Virus-related nuclear, cytoplasmic, and cell membrane antigens were detected in these cells in early in vitro passages by anticomplement and indirect immunofluorescence tests. Infectious virus was rescued from one of the cell sublines after temperature-shock treatment at passage 26. Karyotypic analysis confirmed the human origin of the cells. Control uninfected kidney cancer cells survived only six in vitro passages. The established cells grew to more than 100 in vitro passages 1 year after initiation of the experiments and induced an epithelioid cancer of variable morphology that infiltrated nerves and muscles when inoculated sc into athymic nude mice.", "contents": "Properties of human epithelioid cells established in vitro by a herpesvirus [IBRV(HMC)] isolated from cytomegalovirus-transformed human cells. Infectious bovine rhinotracheitis virus [IBRV(HMC)], a double-enveloped herpesvirus, was isolated from human embryo lung fibroblasts transformed by cytomegalovirus (CMV). This agent was identified as an IBRV strain that was antigenically related to human CMV. Inoculation of a primary human kidney cancer cell culture with IBRV(HMC) resulted in persistent infection and subsequent establishment of a cell line [IBRV(HMC)HKC-1]. Virus-related nuclear, cytoplasmic, and cell membrane antigens were detected in these cells in early in vitro passages by anticomplement and indirect immunofluorescence tests. Infectious virus was rescued from one of the cell sublines after temperature-shock treatment at passage 26. Karyotypic analysis confirmed the human origin of the cells. Control uninfected kidney cancer cells survived only six in vitro passages. The established cells grew to more than 100 in vitro passages 1 year after initiation of the experiments and induced an epithelioid cancer of variable morphology that infiltrated nerves and muscles when inoculated sc into athymic nude mice."}
{"id": "PMID:229293", "title": "Increase in hormonal activation of adenylate cyclase by treatment of cultured cells with N-alkyl,N-nitrosourea.", "content": "Treatment of cultured normal rat kidney cells with the nitrosourea-containing compounds streptozotocin, chlorozotocin, or 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea resulted in a time-dependent potentiation in the ability of prostaglandin E1 and (-)-isoproterenol to elevate intracellular cAMP levels. This hormone response increased at 4 hours and reached a maximum at 15--25 hours after addition of the nitrosoureas. Basal cAMP levels were not affected. The greater response was apparently due to an increase in the GTP-dependent step in hormonal activation of adenylate cyclase, inasmuch as GTP- and GTP plus hormone-stimulated adenylate cyclase activities were enhanced twofold to threefold in crude membranes prepared from nitrosourea-treated cells. Fluoride-stimulated adenylate cyclase activity was increased only 10--25%. Nicotinamide did not prevent the elevated response, and NAD+ plus NADH levels were not appreciably altered after 42 hours; treatment with streptozotocin. The results suggest a possible involvement of cAMP in the biologic actions of nitrosoureas.", "contents": "Increase in hormonal activation of adenylate cyclase by treatment of cultured cells with N-alkyl,N-nitrosourea. Treatment of cultured normal rat kidney cells with the nitrosourea-containing compounds streptozotocin, chlorozotocin, or 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea resulted in a time-dependent potentiation in the ability of prostaglandin E1 and (-)-isoproterenol to elevate intracellular cAMP levels. This hormone response increased at 4 hours and reached a maximum at 15--25 hours after addition of the nitrosoureas. Basal cAMP levels were not affected. The greater response was apparently due to an increase in the GTP-dependent step in hormonal activation of adenylate cyclase, inasmuch as GTP- and GTP plus hormone-stimulated adenylate cyclase activities were enhanced twofold to threefold in crude membranes prepared from nitrosourea-treated cells. Fluoride-stimulated adenylate cyclase activity was increased only 10--25%. Nicotinamide did not prevent the elevated response, and NAD+ plus NADH levels were not appreciably altered after 42 hours; treatment with streptozotocin. The results suggest a possible involvement of cAMP in the biologic actions of nitrosoureas."}
{"id": "PMID:229294", "title": "Immunologic heterogeneity of tumor cell subpopulations from a single mouse mammary tumor.", "content": "Five subpopulations (66, 67, 68H, 168, and 4.10LM) obtained from a single BALB/cfC3H mammary adenocarcinoma were used to assess intratumor immunologic heterogeneity. BALB/c and BALB/cfC3H mice were immunized with each of the subpopulations, and lymph node cells (LNC) from immunized animals were tested for cell-mediated immunity (CMI) to each subpopulation in vitro by chromium release and microcytotoxicity tests and in vivo by Winn assays. The immunogenic character of the subpopulations differed markedly. The pattern of cross-reactivity indicated that at least two determinants were involved, one of which was probably a viral antigen. The viral antigen was expressed on 4 subpopulations (66, 68H, 168, and 4.10LM). The other determinant was immunogenic in both BALB/c and BALB/cfC3H mice and was expressed on 4 subpopulations (66, 67, 168, and 4.10lm). Thus 1 subpopulation (68H) expressed only the viral antigen, 1 (67) expressed only the other antigen, and 3 (66, 168, and 4.10LM) expressed both. Expression of the determinants showed qualitative and quantitative variations. Quantitative differences were noted by the relative effectiveness of the subpopulations to induce CMI and by the relative sensitivities to LNC-mediated killing. Qualitative differences were indicated by the occurrence of unidirectional cross-reactivities between some pairs of subpopulations; a determinant could be expressed so that the subpopulation could induce cytotoxic cells but not be sensitive to them or vice versa.", "contents": "Immunologic heterogeneity of tumor cell subpopulations from a single mouse mammary tumor. Five subpopulations (66, 67, 68H, 168, and 4.10LM) obtained from a single BALB/cfC3H mammary adenocarcinoma were used to assess intratumor immunologic heterogeneity. BALB/c and BALB/cfC3H mice were immunized with each of the subpopulations, and lymph node cells (LNC) from immunized animals were tested for cell-mediated immunity (CMI) to each subpopulation in vitro by chromium release and microcytotoxicity tests and in vivo by Winn assays. The immunogenic character of the subpopulations differed markedly. The pattern of cross-reactivity indicated that at least two determinants were involved, one of which was probably a viral antigen. The viral antigen was expressed on 4 subpopulations (66, 68H, 168, and 4.10LM). The other determinant was immunogenic in both BALB/c and BALB/cfC3H mice and was expressed on 4 subpopulations (66, 67, 168, and 4.10lm). Thus 1 subpopulation (68H) expressed only the viral antigen, 1 (67) expressed only the other antigen, and 3 (66, 168, and 4.10LM) expressed both. Expression of the determinants showed qualitative and quantitative variations. Quantitative differences were noted by the relative effectiveness of the subpopulations to induce CMI and by the relative sensitivities to LNC-mediated killing. Qualitative differences were indicated by the occurrence of unidirectional cross-reactivities between some pairs of subpopulations; a determinant could be expressed so that the subpopulation could induce cytotoxic cells but not be sensitive to them or vice versa."}
{"id": "PMID:229297", "title": "[Cyclic nucleotide content in the adipocytes of rats with spontaneous genetic hypertension. Variations revealed by adrenalectomy].", "content": "The basal content of cAMP and cGMP in isolated adipose cells of rats with spontaneous genetic hypertension (SHR) was studied. No differences were found between SHR rats and animals with normal pressure in the content of cyclic nucleotides. Adrenalectomy changes essentially the content of cAMP and cGMP in the adipocytes, reducing the cAMP/cGMP ratio in the cells to about one half; the content of cAMP and cGMP is greater in the adipocytes of adrenalectomized SHR rats than in those of adrenalectomized animals with normal pressure.", "contents": "[Cyclic nucleotide content in the adipocytes of rats with spontaneous genetic hypertension. Variations revealed by adrenalectomy]. The basal content of cAMP and cGMP in isolated adipose cells of rats with spontaneous genetic hypertension (SHR) was studied. No differences were found between SHR rats and animals with normal pressure in the content of cyclic nucleotides. Adrenalectomy changes essentially the content of cAMP and cGMP in the adipocytes, reducing the cAMP/cGMP ratio in the cells to about one half; the content of cAMP and cGMP is greater in the adipocytes of adrenalectomized SHR rats than in those of adrenalectomized animals with normal pressure."}
{"id": "PMID:229298", "title": "[High-density lipoprotein subfractions and sex hormones in the blood plasma of men 40 to 59].", "content": "Examination of 50 males aged from 40 to 59 years showed that an increase or decrease in the level of cholesterol of high-density lipoproteins (HDLP) occurs mostly at the expense of cholesterol of the HDLP2 subfraction. Changes in the concentration of sex hormones in the blood plasma are attended by a change in the number of HDLP2 particles, evidence of which was a change in the content of HDLP2 cholesterol and phospholipids with the level of HDLP3 cholesterol and phospholipids remaining unaltered. A higher content is attended by a rise in the level of HDLP2 cholesterol and HDLP2 phospholipids. A negative correlation between the level of estradiol and that of triglycerides in blood plasma (r=-0.61; p less than 0.01) and a positive correlation between the content of estradiol and the level of HDLP2 cholesterol and phospholipids (r=+0.34; p less than 0.05 and r=+0.37; p less than 0.05, respectively were revealed in males with estradiol concentration of 1--8 ng/dl. There was no correlation between the above-mentioned values when the concentration of estradiol in blood plasma was higher (8--16 ng/dl). In hypoalphalipoproteinemia and hypertriglyceridemia, the relation in very low density lipoproteins of apoprotein SH, which inhibits lipoprotein lipase, and apoprotein SP, which activates this enzyme, was higher than normal while the relation of these apoproteins in HDLP was lower.", "contents": "[High-density lipoprotein subfractions and sex hormones in the blood plasma of men 40 to 59]. Examination of 50 males aged from 40 to 59 years showed that an increase or decrease in the level of cholesterol of high-density lipoproteins (HDLP) occurs mostly at the expense of cholesterol of the HDLP2 subfraction. Changes in the concentration of sex hormones in the blood plasma are attended by a change in the number of HDLP2 particles, evidence of which was a change in the content of HDLP2 cholesterol and phospholipids with the level of HDLP3 cholesterol and phospholipids remaining unaltered. A higher content is attended by a rise in the level of HDLP2 cholesterol and HDLP2 phospholipids. A negative correlation between the level of estradiol and that of triglycerides in blood plasma (r=-0.61; p less than 0.01) and a positive correlation between the content of estradiol and the level of HDLP2 cholesterol and phospholipids (r=+0.34; p less than 0.05 and r=+0.37; p less than 0.05, respectively were revealed in males with estradiol concentration of 1--8 ng/dl. There was no correlation between the above-mentioned values when the concentration of estradiol in blood plasma was higher (8--16 ng/dl). In hypoalphalipoproteinemia and hypertriglyceridemia, the relation in very low density lipoproteins of apoprotein SH, which inhibits lipoprotein lipase, and apoprotein SP, which activates this enzyme, was higher than normal while the relation of these apoproteins in HDLP was lower."}
{"id": "PMID:229299", "title": "[Characteristics of cholesterol transport by various classes of lipoproteins and their apolipoproteins in hypo- and hyperalphalipoproteinemia].", "content": "The content in the blood plasma of the main apolipoproteins of lipoproteins of very low and low density apo-B and tetramethylurea-soluble apo-LP as well as lipoproteins of high density apo-A and the relation to apo-LP cholesterol of these classes of lipoproteins were studied in 34 males with different levels of alpha-LP cholesterol. It is shown that in hypoalphacholesterolemia the plasma apo-A content is reduced with the cholesterol/apo-A ratio being less than in normoalphacholesterolemia; at the same time, the content in the plasma of total triglycerides, cholesterol, and protein of very low density lipoproteins is increased and cholesterol saturation calculated for protein of very low and low density lipoproteins does not change. In hyperalphacholesterolemia the plasma apo-A content is increased both in the absolute amount and in relation to apo-B and TMU-soluble proteins; the content of cholesterol on apo-A in high density lipoproteins is the same as under normal conditions and higher than in hypoalphacholesterolemia. The results obtained are discussed in association with the data in the literature concerning the functions of lipoproteins and apo-LP in relation to the transport of cholesterol into the vascular wall and its drainage.", "contents": "[Characteristics of cholesterol transport by various classes of lipoproteins and their apolipoproteins in hypo- and hyperalphalipoproteinemia]. The content in the blood plasma of the main apolipoproteins of lipoproteins of very low and low density apo-B and tetramethylurea-soluble apo-LP as well as lipoproteins of high density apo-A and the relation to apo-LP cholesterol of these classes of lipoproteins were studied in 34 males with different levels of alpha-LP cholesterol. It is shown that in hypoalphacholesterolemia the plasma apo-A content is reduced with the cholesterol/apo-A ratio being less than in normoalphacholesterolemia; at the same time, the content in the plasma of total triglycerides, cholesterol, and protein of very low density lipoproteins is increased and cholesterol saturation calculated for protein of very low and low density lipoproteins does not change. In hyperalphacholesterolemia the plasma apo-A content is increased both in the absolute amount and in relation to apo-B and TMU-soluble proteins; the content of cholesterol on apo-A in high density lipoproteins is the same as under normal conditions and higher than in hypoalphacholesterolemia. The results obtained are discussed in association with the data in the literature concerning the functions of lipoproteins and apo-LP in relation to the transport of cholesterol into the vascular wall and its drainage."}
{"id": "PMID:229300", "title": "[Importance of pyrophosphate-99mTc scintigraphy in the diagnosis of acute myocardial infarct].", "content": "Scintigraphy with pyrophosphate 99mTc was performed in 230 patients with various forms of ischemic heart disease and in 15 persons with pain in the region of the heart caused by osteochondrosis of the cervical and thoracic spinal segments or vegetovascular dystonia (control group). It was found that labelled purophosphate accumulated in the myocardium in necrosis of the heart muscle or when coronary insufficiency takes a course in which necrosis of the myocardial cells is quite possible. Positive results of scintigraphy with pyrophosphate 99mTc are not a strict criterion of acute myocardial infarction because they are also encountered in a chronic course of ischemic heart disease and are evidence in this case that \"a state of risk\" has occurred during the disease.", "contents": "[Importance of pyrophosphate-99mTc scintigraphy in the diagnosis of acute myocardial infarct]. Scintigraphy with pyrophosphate 99mTc was performed in 230 patients with various forms of ischemic heart disease and in 15 persons with pain in the region of the heart caused by osteochondrosis of the cervical and thoracic spinal segments or vegetovascular dystonia (control group). It was found that labelled purophosphate accumulated in the myocardium in necrosis of the heart muscle or when coronary insufficiency takes a course in which necrosis of the myocardial cells is quite possible. Positive results of scintigraphy with pyrophosphate 99mTc are not a strict criterion of acute myocardial infarction because they are also encountered in a chronic course of ischemic heart disease and are evidence in this case that \"a state of risk\" has occurred during the disease."}
{"id": "PMID:229302", "title": "Hormone-sensitive adenylate cyclase along the nephron of genetically hypophosphatemic mice.", "content": "The response of the adenylate cyclase (AC) activity to PTH and calcitonin was measured along the nephron of normal (N) and mutant hypophosphatemic (Hyp) mice of the C 57 BL/6J strain, using in vitro single tubule AC microassay. In each experiment, a Hyp mouse was paired to a N mouse from the same litter. In the presence of PTH (10 U/ml), AC activities (femtomoles cAMP per millimeter of tubule per 30-min incubation) were reduced in the proximal convoluted tubule of Hyp mice as compared to N mice in all experiments (448 +/- (SEM) 46 vs. 831 +/- 79, N = 4, P less than 0.01). Some decrease in AC response to PTH also was noted in the cortical portion of the thick ascending limb of the loop of Henle (476 +/- 70 in Hyp mice vs. 719 +/- 83 in N mice, N = 4, P = NS). The Hyp and N AC responses to PTH were similar in the \"bright\" and \"granular\" portions of the distal convoluted tubule (1524 +/- 177 in Hyp mice and 1538 +/- 228 in N mice, N = 4). The other segments tested were not responsive to PTH (except the pars recta of the proximal tubule). In the presence of salmon calcitonin (10 ng/ml), a striking 5- to 12-fold increase in AC activity of the \"bright\" and \"granular\" portions of the distal convoluted tubule was observed in each Hyp mouse as compared to its paired N control (2434 +/- 618 vs. 399 +/- 56, N = 6, P less than 0.01). The AC response to calcitonin was also increased, though to a lesser extnet (Hyp/N = 1.8) in the \"light\" portion of the distal tubule (590 +/- 60 in Hyp and 352 +/- 36 in N mice, P less than 0.01). Other segments of the mouse nephron were also observed to contain calcitonin-sensitive AC, but the responses were of limited magnitude only and were not statistically different in Hyp and N mice. Dose-response curves showed that the decrease of the response to PTH in the proximal tubule as well as the increase of the response to calcitonin in the distal tubule were present in Hyp mice for the whole range of hormone concentrations tested. In both structures, the apparent Km for the cyclase activation by the hormone was similar in the Hyp and its paired N mouse.", "contents": "Hormone-sensitive adenylate cyclase along the nephron of genetically hypophosphatemic mice. The response of the adenylate cyclase (AC) activity to PTH and calcitonin was measured along the nephron of normal (N) and mutant hypophosphatemic (Hyp) mice of the C 57 BL/6J strain, using in vitro single tubule AC microassay. In each experiment, a Hyp mouse was paired to a N mouse from the same litter. In the presence of PTH (10 U/ml), AC activities (femtomoles cAMP per millimeter of tubule per 30-min incubation) were reduced in the proximal convoluted tubule of Hyp mice as compared to N mice in all experiments (448 +/- (SEM) 46 vs. 831 +/- 79, N = 4, P less than 0.01). Some decrease in AC response to PTH also was noted in the cortical portion of the thick ascending limb of the loop of Henle (476 +/- 70 in Hyp mice vs. 719 +/- 83 in N mice, N = 4, P = NS). The Hyp and N AC responses to PTH were similar in the \"bright\" and \"granular\" portions of the distal convoluted tubule (1524 +/- 177 in Hyp mice and 1538 +/- 228 in N mice, N = 4). The other segments tested were not responsive to PTH (except the pars recta of the proximal tubule). In the presence of salmon calcitonin (10 ng/ml), a striking 5- to 12-fold increase in AC activity of the \"bright\" and \"granular\" portions of the distal convoluted tubule was observed in each Hyp mouse as compared to its paired N control (2434 +/- 618 vs. 399 +/- 56, N = 6, P less than 0.01). The AC response to calcitonin was also increased, though to a lesser extnet (Hyp/N = 1.8) in the \"light\" portion of the distal tubule (590 +/- 60 in Hyp and 352 +/- 36 in N mice, P less than 0.01). Other segments of the mouse nephron were also observed to contain calcitonin-sensitive AC, but the responses were of limited magnitude only and were not statistically different in Hyp and N mice. Dose-response curves showed that the decrease of the response to PTH in the proximal tubule as well as the increase of the response to calcitonin in the distal tubule were present in Hyp mice for the whole range of hormone concentrations tested. In both structures, the apparent Km for the cyclase activation by the hormone was similar in the Hyp and its paired N mouse."}
{"id": "PMID:229307", "title": "[Rota virus infection in the newborn and infant -- epidemiological aspects (author's transl)].", "content": "In a total of 406 sera an age-dependent pattern of complement fixing antibodies against Rotavirus (Nebraska calf diarrhea virus) was found: 85% of the adults had antibodies, infants in the second half-year of life had the lowest percentage (42%). Thereupon a Rotavirus survey was carried out in a newborn ward by means of electron microscopy, enzyme-linked immunosorbent assay and complement fixation test during three weeks in January/February 1978. A chronically high infection rate was discovered. Children acquired intestinal infection despite of complement fixing serum antibodies and very few showed a rise in antibody titer.", "contents": "[Rota virus infection in the newborn and infant -- epidemiological aspects (author's transl)]. In a total of 406 sera an age-dependent pattern of complement fixing antibodies against Rotavirus (Nebraska calf diarrhea virus) was found: 85% of the adults had antibodies, infants in the second half-year of life had the lowest percentage (42%). Thereupon a Rotavirus survey was carried out in a newborn ward by means of electron microscopy, enzyme-linked immunosorbent assay and complement fixation test during three weeks in January/February 1978. A chronically high infection rate was discovered. Children acquired intestinal infection despite of complement fixing serum antibodies and very few showed a rise in antibody titer."}
{"id": "PMID:229308", "title": "[Burkitt-like lymphoma: diagnosis, clinical features, and response to chemotherapy (author's transl)].", "content": "The Burkitt-like lymphoma is extremely rare. It shows a predominance of presentation in abdominal and pelvic sites and an older median age as compared to the endemic Burkitt's lymphoma. Both are independent prognostic determinants and reflect a poor prognosis. This might be the reason for the low response rate to cytotoxic treatment. Cyclophosphamide is a substantial part of any chemotherapeutic regimen used. Serum lactic dehydrogenase (LDH) levels are closely correlated with the extent of tumor mass and the response to therapy. Chemotherapy might be associated with serious metabolic complications including hyperkalemia, lactic acidosis, anuria, and sudden death from lethal embolization of the lung. In contrast to Burkitt's lymphoma, the Burkitt-like tumor has no association with the Epstein-Barr-virus. In both lymphomas a translocation from the 8q onto 14q chromosome occurs being a characteristic marker for these malignancies.", "contents": "[Burkitt-like lymphoma: diagnosis, clinical features, and response to chemotherapy (author's transl)]. The Burkitt-like lymphoma is extremely rare. It shows a predominance of presentation in abdominal and pelvic sites and an older median age as compared to the endemic Burkitt's lymphoma. Both are independent prognostic determinants and reflect a poor prognosis. This might be the reason for the low response rate to cytotoxic treatment. Cyclophosphamide is a substantial part of any chemotherapeutic regimen used. Serum lactic dehydrogenase (LDH) levels are closely correlated with the extent of tumor mass and the response to therapy. Chemotherapy might be associated with serious metabolic complications including hyperkalemia, lactic acidosis, anuria, and sudden death from lethal embolization of the lung. In contrast to Burkitt's lymphoma, the Burkitt-like tumor has no association with the Epstein-Barr-virus. In both lymphomas a translocation from the 8q onto 14q chromosome occurs being a characteristic marker for these malignancies."}
{"id": "PMID:229338", "title": "Electron microscopic examination of primate feces for rotaviruses.", "content": "Using electron microscopic procedures known to be capable of detecting rotaviruses, feces from both human and nonhuman primates were examined for the presence of these viruses. Fecal samples were taken from man and animals with and without diarrhea. Rotaviruses were not observed in these specimens.", "contents": "Electron microscopic examination of primate feces for rotaviruses. Using electron microscopic procedures known to be capable of detecting rotaviruses, feces from both human and nonhuman primates were examined for the presence of these viruses. Fecal samples were taken from man and animals with and without diarrhea. Rotaviruses were not observed in these specimens."}
{"id": "PMID:229339", "title": "An enzyme-linked immunosorbent assay for the detection of canine antibodies to canine adenoviruses.", "content": "An enzyme-linked immunosorbent assay was used to detect canine immunoglobulin G antibodies specific for infectious canine hepatitis virus and the serologically related canine adenovirus Type 2. The sequential development of homologous and heterologous antibodies was measured by the enzyme-linked immunosorbent assay and serum neutralization tests in two groups of dogs which were experimentally infected with either infectious canine hepatitis virus or canine adenovirus Type 2. Both tests were comparable in their abilities to detect the development of homologous and heterologous antibodies. Homologous antibodies were detected earlier and to a higher titer in both tests. There was a 98% agreement between the serum neutralization test and the enzyme-linked immunosorbent assay when sera from 224 random-source dogs were examined for infectious canine hepatitis virus antibodies. The enzyme-linked immunosorbent assay was found to be a highly efficient and rapid test to determine the immune status of dogs to infectious canine hepatitis virus and canine adenovirus Type 2.", "contents": "An enzyme-linked immunosorbent assay for the detection of canine antibodies to canine adenoviruses. An enzyme-linked immunosorbent assay was used to detect canine immunoglobulin G antibodies specific for infectious canine hepatitis virus and the serologically related canine adenovirus Type 2. The sequential development of homologous and heterologous antibodies was measured by the enzyme-linked immunosorbent assay and serum neutralization tests in two groups of dogs which were experimentally infected with either infectious canine hepatitis virus or canine adenovirus Type 2. Both tests were comparable in their abilities to detect the development of homologous and heterologous antibodies. Homologous antibodies were detected earlier and to a higher titer in both tests. There was a 98% agreement between the serum neutralization test and the enzyme-linked immunosorbent assay when sera from 224 random-source dogs were examined for infectious canine hepatitis virus antibodies. The enzyme-linked immunosorbent assay was found to be a highly efficient and rapid test to determine the immune status of dogs to infectious canine hepatitis virus and canine adenovirus Type 2."}
{"id": "PMID:229340", "title": "Virus detection in monkeys with diarrhea: the association of adenoviruses with diarrhea and the possible role of rotaviruses.", "content": "To explore the role of viruses in the etiology of diarrhea in colony-reared monkeys, direct electron microscopy, the fluorescent virus precipitin test and cell culture inoculation were used to examine the stools of monkeys with and without diarrhea. The animals were predominantly rhesus with a few macaques of other species, and included infants, juveniles and adults. Adenoviruses were isolated from a higher proportion of specimens from rhesus monkeys with diarrhea (73% of specimens from infants and 78% of specimens from juveniles and adults) than from control monkeys without diarrhea (22% of specimens from infants and 26% of specimens from juveniles and adults). SV 20 was the most frequently isolated simian adenovirus type; SV 17 and SV 32 also were recovered. Noncultivable adenoviruses detectable only by electron microscopy were not seen. Although adenovirus excretion was associated with diarrhea, the causal role of adenoviruses was difficult to assess. When serial specimens from animals with chronic or intermittent episodes of diarrhea were examined, sequential infections with different viruses were found to be common. Rotaviruses were detected by electron microscopy and isolated in cell cultures from two infant rhesus monkeys with diarrhea. However, the low detection rate, together with negative serologic data on 40% of infant monkeys with diarrhea, suggested that rotaviruses were not the major cause of gastroenteritis in the monkeys under study.", "contents": "Virus detection in monkeys with diarrhea: the association of adenoviruses with diarrhea and the possible role of rotaviruses. To explore the role of viruses in the etiology of diarrhea in colony-reared monkeys, direct electron microscopy, the fluorescent virus precipitin test and cell culture inoculation were used to examine the stools of monkeys with and without diarrhea. The animals were predominantly rhesus with a few macaques of other species, and included infants, juveniles and adults. Adenoviruses were isolated from a higher proportion of specimens from rhesus monkeys with diarrhea (73% of specimens from infants and 78% of specimens from juveniles and adults) than from control monkeys without diarrhea (22% of specimens from infants and 26% of specimens from juveniles and adults). SV 20 was the most frequently isolated simian adenovirus type; SV 17 and SV 32 also were recovered. Noncultivable adenoviruses detectable only by electron microscopy were not seen. Although adenovirus excretion was associated with diarrhea, the causal role of adenoviruses was difficult to assess. When serial specimens from animals with chronic or intermittent episodes of diarrhea were examined, sequential infections with different viruses were found to be common. Rotaviruses were detected by electron microscopy and isolated in cell cultures from two infant rhesus monkeys with diarrhea. However, the low detection rate, together with negative serologic data on 40% of infant monkeys with diarrhea, suggested that rotaviruses were not the major cause of gastroenteritis in the monkeys under study."}
{"id": "PMID:229341", "title": "Studies on sphingomyelinase activity in cultured cells and leucocytes.", "content": "Using both [3H]ceramide-sphingomyelin and [14C]methyl choline-sphingomyelin as substrate, enzyme activity was determined in skin fibroblasts, cultured amniotic fluid cells and leucocytes. Sphingomyelinase activities of fibroblasts from two patients with Niemann-Pick disease were about 1% of the mean control values (22.9 nmol/h/mg protein and 65.6 nmol/h/mg protein, with [3H]sphingomyelin and [14C]sphingomyelin respectively). Leucocyte sphingomyelinase activity is much lower than that of cultured cells. Optimum sphingomyelinase activity of cultured cells is at pH 5.0 and the apparent Km values are 58 mumol/1 and about 200 mumol/1 for [3H]sphingomyelin and [14C]sphingomyelin respectively. These properties are similar to those for residual sphingomyelinase activity in Niemann-Pick fibroblasts.", "contents": "Studies on sphingomyelinase activity in cultured cells and leucocytes. Using both [3H]ceramide-sphingomyelin and [14C]methyl choline-sphingomyelin as substrate, enzyme activity was determined in skin fibroblasts, cultured amniotic fluid cells and leucocytes. Sphingomyelinase activities of fibroblasts from two patients with Niemann-Pick disease were about 1% of the mean control values (22.9 nmol/h/mg protein and 65.6 nmol/h/mg protein, with [3H]sphingomyelin and [14C]sphingomyelin respectively). Leucocyte sphingomyelinase activity is much lower than that of cultured cells. Optimum sphingomyelinase activity of cultured cells is at pH 5.0 and the apparent Km values are 58 mumol/1 and about 200 mumol/1 for [3H]sphingomyelin and [14C]sphingomyelin respectively. These properties are similar to those for residual sphingomyelinase activity in Niemann-Pick fibroblasts."}
{"id": "PMID:229342", "title": "Anderson-Fabry disease: rapid detection of carriers by hair bulb analysis.", "content": "A rapid and simple method is described for the identification of the carrier state in angiokeratoma corporis diffusum. The alpha-galactosidase (alpha-D-galactoside galactohydrolase, E.C.3.2.1.22) activities in individual hair roots are measured and compared with those of N-acetyl-beta-hexosaminidase (E.C.3.2.1.30), another lysosomal enzyme that is not affected. The cellular mosaicism typical of females heterozygous for X-linked disorders is revealed by the presence of normal, affected and partially affected hair roots. Normal individuals show no affected roots, while males hemizygous for the trait have no hair roots with enzyme activities in the normal range.", "contents": "Anderson-Fabry disease: rapid detection of carriers by hair bulb analysis. A rapid and simple method is described for the identification of the carrier state in angiokeratoma corporis diffusum. The alpha-galactosidase (alpha-D-galactoside galactohydrolase, E.C.3.2.1.22) activities in individual hair roots are measured and compared with those of N-acetyl-beta-hexosaminidase (E.C.3.2.1.30), another lysosomal enzyme that is not affected. The cellular mosaicism typical of females heterozygous for X-linked disorders is revealed by the presence of normal, affected and partially affected hair roots. Normal individuals show no affected roots, while males hemizygous for the trait have no hair roots with enzyme activities in the normal range."}
{"id": "PMID:229343", "title": "Cyclic adenosine monophosphate excretion in urine of patients and carriers of congenital nephrogenic diabetes insipidus.", "content": "Urinary excretion of cyclic adenosine monophosphate (cAMP) is assessed in response to pitressin stimulation in three patients with nephrogenic diabetes insipidus, four carriers and seven controls. There is no significant difference in cAMP excretion between these groups when corrected for surface area, nor is there any significant increase in excretion after pitressin stimulation. There is very close correlation between urinary cAMP and both urinary concentration and urinary creatinine excretion. Urinary cAMP after pitressin stimulation does not discriminate between carriers of nephrogenic diabetes insipidus and control subjects.", "contents": "Cyclic adenosine monophosphate excretion in urine of patients and carriers of congenital nephrogenic diabetes insipidus. Urinary excretion of cyclic adenosine monophosphate (cAMP) is assessed in response to pitressin stimulation in three patients with nephrogenic diabetes insipidus, four carriers and seven controls. There is no significant difference in cAMP excretion between these groups when corrected for surface area, nor is there any significant increase in excretion after pitressin stimulation. There is very close correlation between urinary cAMP and both urinary concentration and urinary creatinine excretion. Urinary cAMP after pitressin stimulation does not discriminate between carriers of nephrogenic diabetes insipidus and control subjects."}
{"id": "PMID:229344", "title": "Disordered intestinal function in glycogen storage disease.", "content": "The classical features of Type I glycogen storage disease (McKusick 23220) (GSD) are hepatomegaly, hypoglycaemia, and acidosis, enlargement of the kidneys and short stature. Glucose-6-phosphatase (EC 3.1.3.9) activity is defective not only in liver and kidney but also in small intestine (Field et al., 1965). In addition to the classical features, many patients suffer from episodes of diarrhoea (Fine et al., 1969). At the Hospital for Sick Children, Great Ormond Street, patients with the commoner forms of hepatic glycogen storage disease have episodes of diarrhoea or loose stools more commonly than was suspected. We have investigated small intestinal function in three patients with Type I GSD by both in vitro and in vivo techniques.", "contents": "Disordered intestinal function in glycogen storage disease. The classical features of Type I glycogen storage disease (McKusick 23220) (GSD) are hepatomegaly, hypoglycaemia, and acidosis, enlargement of the kidneys and short stature. Glucose-6-phosphatase (EC 3.1.3.9) activity is defective not only in liver and kidney but also in small intestine (Field et al., 1965). In addition to the classical features, many patients suffer from episodes of diarrhoea (Fine et al., 1969). At the Hospital for Sick Children, Great Ormond Street, patients with the commoner forms of hepatic glycogen storage disease have episodes of diarrhoea or loose stools more commonly than was suspected. We have investigated small intestinal function in three patients with Type I GSD by both in vitro and in vivo techniques."}
{"id": "PMID:229356", "title": "Structure of the DNA binding cleft of the gene 5 protein from bacteriophage fd.", "content": "The structure of the gene 5 DNA unwinding protein from bacteriophage fd has been solved to 2.3-A resolution by X-ray diffraction techniques. The molecule contains an extensive cleft region that we have identified as the DNA binding site on the basis of the residues that comprise its surface. The interior of the groove has a rather large number of basic amino acid residues that serve to draw the polynucleotide backbone into the cleft. Arrayed along the external edges of the groove are a number of aromatic amino acid side groups that are in position to stack upon the bases of the DNA and fix it in place. The structure and binding mechanism as we visualize it appear to be fully consistent with evidence provided by physical-chemical studies of the protein in solution.", "contents": "Structure of the DNA binding cleft of the gene 5 protein from bacteriophage fd. The structure of the gene 5 DNA unwinding protein from bacteriophage fd has been solved to 2.3-A resolution by X-ray diffraction techniques. The molecule contains an extensive cleft region that we have identified as the DNA binding site on the basis of the residues that comprise its surface. The interior of the groove has a rather large number of basic amino acid residues that serve to draw the polynucleotide backbone into the cleft. Arrayed along the external edges of the groove are a number of aromatic amino acid side groups that are in position to stack upon the bases of the DNA and fix it in place. The structure and binding mechanism as we visualize it appear to be fully consistent with evidence provided by physical-chemical studies of the protein in solution."}
{"id": "PMID:229357", "title": "Reconstituted low density lipoprotein: a vehicle for the delivery of hydrophobic fluorescent probes to cells.", "content": "Previous studies have shown that the cholesteryl ester core of plasma low density lipoprotein (LDL) can be extracted with heptane and replaced with a variety of hydrophobic molecules. In the present report we use this reconstitution technique to incorporate two fluorescent probes, 3-pyrenemethyl-23, 24-dinor-5-cholen-22-oate-3 beta-yl oleate (PMCA oleate) and dioleyl fluorescein, into heptane-extracted LDL. Both fluorescent lipoprotein preparations were shown to be useful probes for visualizing the receptor-mediated endocytosis of LDL in cultured human fibroblasts. When normal fibroblasts were incubated at 37 degrees C with either of the fluorescent LDL preparations, fluorescent granules accumulated in the perinuclear region of the cell. In contrast, fibroblasts from patients with the homozygous form of familial hypercholesterolemia (FH) that lack functional LDL receptors did not accumulate visible fluorescent granules when incubated with the fluorescent reconstituted LDL. A fluorescence-activated cell sorter was used to quantify the fluorescence intensity of individual cells that had been incubated with LDL reconstituted with dioleyl fluorescein. With this technique a population of normal fibroblasts could be distinguished from a population of FH fibroblasts. The current studies demonstrate the feasibility of using fluorescent reconstituted LDL in conjunction with the cell sorter to isolate mutant cells lacking functional LDL receptors.", "contents": "Reconstituted low density lipoprotein: a vehicle for the delivery of hydrophobic fluorescent probes to cells. Previous studies have shown that the cholesteryl ester core of plasma low density lipoprotein (LDL) can be extracted with heptane and replaced with a variety of hydrophobic molecules. In the present report we use this reconstitution technique to incorporate two fluorescent probes, 3-pyrenemethyl-23, 24-dinor-5-cholen-22-oate-3 beta-yl oleate (PMCA oleate) and dioleyl fluorescein, into heptane-extracted LDL. Both fluorescent lipoprotein preparations were shown to be useful probes for visualizing the receptor-mediated endocytosis of LDL in cultured human fibroblasts. When normal fibroblasts were incubated at 37 degrees C with either of the fluorescent LDL preparations, fluorescent granules accumulated in the perinuclear region of the cell. In contrast, fibroblasts from patients with the homozygous form of familial hypercholesterolemia (FH) that lack functional LDL receptors did not accumulate visible fluorescent granules when incubated with the fluorescent reconstituted LDL. A fluorescence-activated cell sorter was used to quantify the fluorescence intensity of individual cells that had been incubated with LDL reconstituted with dioleyl fluorescein. With this technique a population of normal fibroblasts could be distinguished from a population of FH fibroblasts. The current studies demonstrate the feasibility of using fluorescent reconstituted LDL in conjunction with the cell sorter to isolate mutant cells lacking functional LDL receptors."}
{"id": "PMID:229358", "title": "Preliminary molecular replacement results for a crystalline gene 4 protein-deoxyoligonucleotide complex.", "content": "Complexes of the gene 5 protein from bacteriophage fd with a variety of oligodeoxynucleotides, ranging in length from two to eight and comprised of several different sequences, have been formed and crystallized for X-ray diffraction analysis. The crystallographic parameters of four different unit cells, all of which are based on hexagonal packing arrangements, indicate that the fundamental unit of the complex is composed of six gene 5 protein dimers. We believe this aggregate has 622 point group symmetry and is a ring formed by end-to-end closure of a linear array of six dimers. From our results we have proposed a double-helix model for the gene 5 protein-DNA complex in which the protein forms a spindle or core around which the DNA is spooled. Currently 5.0-A X-ray diffraction data from one of the crystalline complexes is being analyzed by molecular replacement techniques to obtain a direct image of the protein-nucleic acid complex.", "contents": "Preliminary molecular replacement results for a crystalline gene 4 protein-deoxyoligonucleotide complex. Complexes of the gene 5 protein from bacteriophage fd with a variety of oligodeoxynucleotides, ranging in length from two to eight and comprised of several different sequences, have been formed and crystallized for X-ray diffraction analysis. The crystallographic parameters of four different unit cells, all of which are based on hexagonal packing arrangements, indicate that the fundamental unit of the complex is composed of six gene 5 protein dimers. We believe this aggregate has 622 point group symmetry and is a ring formed by end-to-end closure of a linear array of six dimers. From our results we have proposed a double-helix model for the gene 5 protein-DNA complex in which the protein forms a spindle or core around which the DNA is spooled. Currently 5.0-A X-ray diffraction data from one of the crystalline complexes is being analyzed by molecular replacement techniques to obtain a direct image of the protein-nucleic acid complex."}
{"id": "PMID:229363", "title": "Facial nerve function in 100 consecutive parotidectomies.", "content": "The risk of facial nerve paresis after parotidectomy is thought to be within acceptable limits, although it is difficult to find published data regarding the specific magnitude of this risk. This study reviews the subject and reports postoperative facial function in 100 consecutive patients who had parotidectomies at the Henry Ford Hospital during a 9-year period. Permanent weakness of a major branch was identified in 2 of 77 patients having lateral lobectomy for parotid disease. Both patients demonstrated marginal mandibular paresis after surgery for adenolymphoma. No weakness was noted in 16 patients undergoing total parotidectomy. No unanticipated nerve disability was noted in 4 patients having partial nerve sacrifice in extended procedures; 3 patients had complete sacrifice of the nerve.", "contents": "Facial nerve function in 100 consecutive parotidectomies. The risk of facial nerve paresis after parotidectomy is thought to be within acceptable limits, although it is difficult to find published data regarding the specific magnitude of this risk. This study reviews the subject and reports postoperative facial function in 100 consecutive patients who had parotidectomies at the Henry Ford Hospital during a 9-year period. Permanent weakness of a major branch was identified in 2 of 77 patients having lateral lobectomy for parotid disease. Both patients demonstrated marginal mandibular paresis after surgery for adenolymphoma. No weakness was noted in 16 patients undergoing total parotidectomy. No unanticipated nerve disability was noted in 4 patients having partial nerve sacrifice in extended procedures; 3 patients had complete sacrifice of the nerve."}
{"id": "PMID:229364", "title": "The \"missing\" investigation of Legionnaires' disease.", "content": "The investigation of Legionnaires' disease was riddled with problems, and as a result, was largely ineffective. But the lesions it taught can be extremely valuable to future public-health efforts if they are heeded. This chapter has attempted to highlight those problems and offer some possible solutions. It is now up to the public-health hierarchy to use what is offered in these pages to spark the building of programs and systems that provide the level of effectiveness the American people have a right to expect from public-health departments. Finally, it was my intent to raise questions about the Center for Disease Control's new organism. The Center may, indeed, have found the responsible agent. We must not, however, allow ourselves to have tunnel vision in the continuing investigation--switching to other possibilities only if the microorganism theory is exhausted. The evidence and remaining questions demand a broader scope of investigation. How tragic it will be if we have not learned from the inflexibility and narrowness of the 1976 investigation of Legionnaires' disease.", "contents": "The \"missing\" investigation of Legionnaires' disease. The investigation of Legionnaires' disease was riddled with problems, and as a result, was largely ineffective. But the lesions it taught can be extremely valuable to future public-health efforts if they are heeded. This chapter has attempted to highlight those problems and offer some possible solutions. It is now up to the public-health hierarchy to use what is offered in these pages to spark the building of programs and systems that provide the level of effectiveness the American people have a right to expect from public-health departments. Finally, it was my intent to raise questions about the Center for Disease Control's new organism. The Center may, indeed, have found the responsible agent. We must not, however, allow ourselves to have tunnel vision in the continuing investigation--switching to other possibilities only if the microorganism theory is exhausted. The evidence and remaining questions demand a broader scope of investigation. How tragic it will be if we have not learned from the inflexibility and narrowness of the 1976 investigation of Legionnaires' disease."}
{"id": "PMID:229378", "title": "Effect of serum lipoproteins of bile obstructed rats on 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in perfused rat liver.", "content": "Total lipoproteins as well as fractionated VLDL + LDL and HDL from fasted control rats and bile-ligated rats were tested in liver perfusion for their effect on 3-hydroxy-3-methylglutaryl CoA reductase activity in normal rat livers. The total lipoproteins of bile-obstructed rats had 3 times greater capacity to increase 3-hydroxy-3-methylglutaryl CoA reductase activity than that of the control total lipoproteins. When the fractionated lipoproteins were tested from fasted control rats, it was found that the major stimulating activity was in the HDL fraction with minor activity in the VLDL + LDL fraction. When these plasma components isolated from fasted bile-ligated rats were tested, it was found that the major activity had shifted to the VLDL + LDL fraction with the HDL having only a minor stimulatory role. The possible mechanism of action of the abnormal lipoproteins associated with bile obstruction in regulating 3-hydroxy-3-methylglutaryl CoA reductase activity is discussed.", "contents": "Effect of serum lipoproteins of bile obstructed rats on 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in perfused rat liver. Total lipoproteins as well as fractionated VLDL + LDL and HDL from fasted control rats and bile-ligated rats were tested in liver perfusion for their effect on 3-hydroxy-3-methylglutaryl CoA reductase activity in normal rat livers. The total lipoproteins of bile-obstructed rats had 3 times greater capacity to increase 3-hydroxy-3-methylglutaryl CoA reductase activity than that of the control total lipoproteins. When the fractionated lipoproteins were tested from fasted control rats, it was found that the major stimulating activity was in the HDL fraction with minor activity in the VLDL + LDL fraction. When these plasma components isolated from fasted bile-ligated rats were tested, it was found that the major activity had shifted to the VLDL + LDL fraction with the HDL having only a minor stimulatory role. The possible mechanism of action of the abnormal lipoproteins associated with bile obstruction in regulating 3-hydroxy-3-methylglutaryl CoA reductase activity is discussed."}
{"id": "PMID:229382", "title": "[Experimental silicosis. I. Fibrogenic activity of quartz material used in the ceramic industry].", "content": "A high concentration of silica dust in the air many workstands in ceramic plants is a serious risk for the health of exposed workers. It can cause the development of silicosis. The aim of this paper is to evaluate a fibrogenic activity of dusts containing 98% crystalline silica. The ceramic masses have about 25% of Quartz. The samples of 2 lode quartz and 4 sand quartz originated from different mines in Poland were used for the experiment. Their physical properties were analysed by X-ray diffraction and SiO2 content was determined by colorimetry. Their biological aggresiveness was characterised by wet weight, hydroxyproline content, lipid level in the lungs and wet weight of mediastinal lymph nodes of rats which were intratracheally given of the dusts. The results show that the tested dusts have a moderated fibrogenic activity. At short time (3 months) after their administration the fibrogenic changes in lungs were different depending on the kind of dusts, but at the 6th month of the experiment they did not differ at all. The exposition of workers to silica dusts is a great occupational hazard.", "contents": "[Experimental silicosis. I. Fibrogenic activity of quartz material used in the ceramic industry]. A high concentration of silica dust in the air many workstands in ceramic plants is a serious risk for the health of exposed workers. It can cause the development of silicosis. The aim of this paper is to evaluate a fibrogenic activity of dusts containing 98% crystalline silica. The ceramic masses have about 25% of Quartz. The samples of 2 lode quartz and 4 sand quartz originated from different mines in Poland were used for the experiment. Their physical properties were analysed by X-ray diffraction and SiO2 content was determined by colorimetry. Their biological aggresiveness was characterised by wet weight, hydroxyproline content, lipid level in the lungs and wet weight of mediastinal lymph nodes of rats which were intratracheally given of the dusts. The results show that the tested dusts have a moderated fibrogenic activity. At short time (3 months) after their administration the fibrogenic changes in lungs were different depending on the kind of dusts, but at the 6th month of the experiment they did not differ at all. The exposition of workers to silica dusts is a great occupational hazard."}
{"id": "PMID:229383", "title": "Regional differences in the control of lipolysis in human adipose tissue.", "content": "Omental fat cells were 30% smaller than those in subcutaneous regions. In omental fat cells with a mean diameter of 95 mu, the basal cAMP concentration was 50% lower, but the basal rate of glycerol release was three times as rapid as in subcutaneous (epigastric) fat cells of identical size. Added at maximal effective concentration, noradrenaline increased the level of cAMP and the rate of glycerol release more markedly in the omental than in the subcutaneous adipocytes, whereas the response to isopropyl noradrenaline was similar. Before starvation the lipolytic effects of noradrenaline and isopropyl noradrenaline, respectively, were identical in the two regions of subcutaneous adipose tissue investigated (femoral and hypogastric). The findings were well related to the tissue levels of cAMP induced by the two agents. During starvation noradrenaline and isopropyl noradrenaline increased the cAMP level and the rate of lipolysis in fat cells obtained from the hypogastric region, whereas noradrenaline decreased these parameters in femoral adipocytes. Starvation was associated with a more prominent inhibitory effect of phenylephrine on basal and isopropyl-noradrenaline-induced lipolysis in femoral than in hypogastric adipose tissue. In conclusion, differences exist between different regions of adipose tissue in their lipolytic responsiveness to noradrenaline, which seems related to the balance between alpha- and beta-adrenergic receptor response.", "contents": "Regional differences in the control of lipolysis in human adipose tissue. Omental fat cells were 30% smaller than those in subcutaneous regions. In omental fat cells with a mean diameter of 95 mu, the basal cAMP concentration was 50% lower, but the basal rate of glycerol release was three times as rapid as in subcutaneous (epigastric) fat cells of identical size. Added at maximal effective concentration, noradrenaline increased the level of cAMP and the rate of glycerol release more markedly in the omental than in the subcutaneous adipocytes, whereas the response to isopropyl noradrenaline was similar. Before starvation the lipolytic effects of noradrenaline and isopropyl noradrenaline, respectively, were identical in the two regions of subcutaneous adipose tissue investigated (femoral and hypogastric). The findings were well related to the tissue levels of cAMP induced by the two agents. During starvation noradrenaline and isopropyl noradrenaline increased the cAMP level and the rate of lipolysis in fat cells obtained from the hypogastric region, whereas noradrenaline decreased these parameters in femoral adipocytes. Starvation was associated with a more prominent inhibitory effect of phenylephrine on basal and isopropyl-noradrenaline-induced lipolysis in femoral than in hypogastric adipose tissue. In conclusion, differences exist between different regions of adipose tissue in their lipolytic responsiveness to noradrenaline, which seems related to the balance between alpha- and beta-adrenergic receptor response."}
{"id": "PMID:229384", "title": "Anion transport in red blood cells. I. Chemical properties of anion recognition sites as revealed by structure-activity relationships of aromatic sulfonic acids.", "content": "The present study is concerned with the chemical factors that determine the inhibitory properties of reversible aromatic sulfonic acids on sulfate exchange system of human red blood cells. Two series of compounds were tested for inhibitory potencies: benzene sulfonic acid (BS) and 2,2'-disulfonic stilbene (DS) derivatives, each series with substituent groups such as Cl, OH, NH2, NO2, NNN, N-acetamido, and N-benzoamido. As judged by various kinetic criteria, all congeners of BS and DS appear to have common sites of action in the anion transport system. The range of inhibitory potencies, as defined by the concentration required to produce 50% inhibition (ID50), varied over a 10(4) range (ID50:2-50,000 microM). The degree of inhibition was correlated with two physicochemical properties of the substituent groups: (a) lipophilicity, as judged by the pi values (Hansch factor) of the groups; and (b) the electronic character, as judged by sigma values (Hammett factor) of the groups. Optimal correlations were obtained with a linear combination of the two factors. Based on the above structure-activity relationships and on a comparison between the inhibitory properties of congeners of BS and DS, we suggest that the microenvironment of substrate recognition sites bears a positive multipolar character and possesses functionally essential groups with electron donor capacity embedded in a hydrophobic area.", "contents": "Anion transport in red blood cells. I. Chemical properties of anion recognition sites as revealed by structure-activity relationships of aromatic sulfonic acids. The present study is concerned with the chemical factors that determine the inhibitory properties of reversible aromatic sulfonic acids on sulfate exchange system of human red blood cells. Two series of compounds were tested for inhibitory potencies: benzene sulfonic acid (BS) and 2,2'-disulfonic stilbene (DS) derivatives, each series with substituent groups such as Cl, OH, NH2, NO2, NNN, N-acetamido, and N-benzoamido. As judged by various kinetic criteria, all congeners of BS and DS appear to have common sites of action in the anion transport system. The range of inhibitory potencies, as defined by the concentration required to produce 50% inhibition (ID50), varied over a 10(4) range (ID50:2-50,000 microM). The degree of inhibition was correlated with two physicochemical properties of the substituent groups: (a) lipophilicity, as judged by the pi values (Hansch factor) of the groups; and (b) the electronic character, as judged by sigma values (Hammett factor) of the groups. Optimal correlations were obtained with a linear combination of the two factors. Based on the above structure-activity relationships and on a comparison between the inhibitory properties of congeners of BS and DS, we suggest that the microenvironment of substrate recognition sites bears a positive multipolar character and possesses functionally essential groups with electron donor capacity embedded in a hydrophobic area."}
{"id": "PMID:229385", "title": "Anion transport in red blood cells. II. Kinetics of reversible inhibition by nitroaromatic sulfonic acids.", "content": "The anion exchange system of human red blood cells is highly inhibited and specifically labeled by isothiocyano derivatives of benzene sulfonate (BS) or stilbene disulfonate (DS). To learn about the site of action of these irreversibly binding probes we studied the mechanism of inhibition of anion exchange by the reversibly binding analogs p-nitrobenzene sulfonic acid (pNBS) and 4,4'-dinitrostilbene-disulfonic acid (DNDS). In the absence of inhibitor, the self-exchange flux of sulfate (pH 7.4, 25 degrees C) at high substrate concentration displayed self-inhibitory properties, indicating the existence of two anion binding sites: one a high-affinity transport site and the other a low-affinity modifier site whose occupancy by anions results in a noncompetitive inhibition of transport. The maximal sulfate exchange flux per unit area was JA = (0.69 +/- 0.11) X 10(-10) moles . min-1 . cm-2 and the Michaelis-Menten constants were for the transport site KS = 41 +/- 14 mM and for the modifier site Ks' = 653 +/- 242 mM. The addition to cells of either pNBS at millimolar concentrations or DNDS at micromolar concentrations led to reversible inhibition of sulfate exchange (pH 7.4, 25 degrees C). The relationship between inhibitor concentration and fractional inhibition was linear over the full range of pNBS or DNDS concentrations (Hill coefficient n approximately equal to 1), indicating a single site of inhibition for the two probes. The kinetics of sulfate exchange in the presence of either inhibitor was compatible with that of competitive inhibition. Using various analytical techniques it was possible to determine that the sulfate transport site was the target for the action of the inhibitors. The inhibitory constants (Ki) for the transport sites were 0.45 +/- 0.10 microM for DNDS and 0.21 +/- 0.07 mM for pNBS. From the similarities between reversibly and irreversibly binding BS and DS inhibitors in structures, chemical properties, modus operandi, stoichiometry of interaction with inhibitory sites, and relative inhibitory potencies, we concluded that the anion transport sites are also the sites of inhibition and of labeling of covalent binding analogs of BS and DS.", "contents": "Anion transport in red blood cells. II. Kinetics of reversible inhibition by nitroaromatic sulfonic acids. The anion exchange system of human red blood cells is highly inhibited and specifically labeled by isothiocyano derivatives of benzene sulfonate (BS) or stilbene disulfonate (DS). To learn about the site of action of these irreversibly binding probes we studied the mechanism of inhibition of anion exchange by the reversibly binding analogs p-nitrobenzene sulfonic acid (pNBS) and 4,4'-dinitrostilbene-disulfonic acid (DNDS). In the absence of inhibitor, the self-exchange flux of sulfate (pH 7.4, 25 degrees C) at high substrate concentration displayed self-inhibitory properties, indicating the existence of two anion binding sites: one a high-affinity transport site and the other a low-affinity modifier site whose occupancy by anions results in a noncompetitive inhibition of transport. The maximal sulfate exchange flux per unit area was JA = (0.69 +/- 0.11) X 10(-10) moles . min-1 . cm-2 and the Michaelis-Menten constants were for the transport site KS = 41 +/- 14 mM and for the modifier site Ks' = 653 +/- 242 mM. The addition to cells of either pNBS at millimolar concentrations or DNDS at micromolar concentrations led to reversible inhibition of sulfate exchange (pH 7.4, 25 degrees C). The relationship between inhibitor concentration and fractional inhibition was linear over the full range of pNBS or DNDS concentrations (Hill coefficient n approximately equal to 1), indicating a single site of inhibition for the two probes. The kinetics of sulfate exchange in the presence of either inhibitor was compatible with that of competitive inhibition. Using various analytical techniques it was possible to determine that the sulfate transport site was the target for the action of the inhibitors. The inhibitory constants (Ki) for the transport sites were 0.45 +/- 0.10 microM for DNDS and 0.21 +/- 0.07 mM for pNBS. From the similarities between reversibly and irreversibly binding BS and DS inhibitors in structures, chemical properties, modus operandi, stoichiometry of interaction with inhibitory sites, and relative inhibitory potencies, we concluded that the anion transport sites are also the sites of inhibition and of labeling of covalent binding analogs of BS and DS."}
{"id": "PMID:229387", "title": "Fructose-1,6-diphosphatase: a cellular site of hyperbaric oxygen toxicity.", "content": "The growth-inhibitory effect of 4.2 atm of hyperbaric oxygen for Escherichia coli was strongly influenced by available nutrients. A pattern of protection was achieved with various carbohydrate intermediates which was consistent with oxygen-induced poisoning of fructose-1,6-diphosphatase and of enzymes required in the pentose shunt and for converting galactose into glucose. Two of these sites have not been investigated further, but direct evidence was obtained that purified fructose-1,6-diphosphatase was inactivated in vitro by superoxide anion, but not by molecular oxygen at hyperbaric pressure (4.2 atm). Poisioning of fructose-1,6-diphosphatase by metabolically generated oxygen radicals, such as superoxide ion, would have deleterious effects for E. coli in media where synthesis of glucose by reverse glycolysis is required, and presumably for cells of higher organisms, including man.", "contents": "Fructose-1,6-diphosphatase: a cellular site of hyperbaric oxygen toxicity. The growth-inhibitory effect of 4.2 atm of hyperbaric oxygen for Escherichia coli was strongly influenced by available nutrients. A pattern of protection was achieved with various carbohydrate intermediates which was consistent with oxygen-induced poisoning of fructose-1,6-diphosphatase and of enzymes required in the pentose shunt and for converting galactose into glucose. Two of these sites have not been investigated further, but direct evidence was obtained that purified fructose-1,6-diphosphatase was inactivated in vitro by superoxide anion, but not by molecular oxygen at hyperbaric pressure (4.2 atm). Poisioning of fructose-1,6-diphosphatase by metabolically generated oxygen radicals, such as superoxide ion, would have deleterious effects for E. coli in media where synthesis of glucose by reverse glycolysis is required, and presumably for cells of higher organisms, including man."}
{"id": "PMID:229388", "title": "The role of macrophages in the early resistance to mouse hepatitus virus infection in nude mice.", "content": "Nude mice which had received intraperitoneal injection of silica simultaneously with infection of mouse hepatitis virus, NuU strain, died of severe necrotic hepatitis within 2 weeks postinfection, whereas those having received no silica survived for 3 weeks or more after challenge. Silica given day 4 postinoculation had no effect. The virus titers of the liver and spleen at day 4 as well as serum interferon levels at day 2 were much higher in silica-treated mice than those without silica treatment. At day 2 or 3 postinoculation, silica-treated mice were found to have a considerable number of necrotic foci in the liver with some neutrophil and lymphocyte infiltration, and viral antigen was present in the cytoplasm of some hepatocytes around necrotic foci. In contrast, those without silica treatment showed only some necrotic foci with some lymphocyte infiltration. Viral antigen was detected only in a few littoral cells but not in hepatocytes. The role of macrophages in the resistance at early stage of inection in nude mice is discussed.", "contents": "The role of macrophages in the early resistance to mouse hepatitus virus infection in nude mice. Nude mice which had received intraperitoneal injection of silica simultaneously with infection of mouse hepatitis virus, NuU strain, died of severe necrotic hepatitis within 2 weeks postinfection, whereas those having received no silica survived for 3 weeks or more after challenge. Silica given day 4 postinoculation had no effect. The virus titers of the liver and spleen at day 4 as well as serum interferon levels at day 2 were much higher in silica-treated mice than those without silica treatment. At day 2 or 3 postinoculation, silica-treated mice were found to have a considerable number of necrotic foci in the liver with some neutrophil and lymphocyte infiltration, and viral antigen was present in the cytoplasm of some hepatocytes around necrotic foci. In contrast, those without silica treatment showed only some necrotic foci with some lymphocyte infiltration. Viral antigen was detected only in a few littoral cells but not in hepatocytes. The role of macrophages in the resistance at early stage of inection in nude mice is discussed."}
{"id": "PMID:229389", "title": "Studies on the neutralization of herpes simplex virus. X. Demonstration of complement-requiring neutralizing (CRN) and slow-reacting CRN (s-CRN) antibodies in late IgG.", "content": "A sample of late IgG from a rabbit hyperimmunized with herpes simplex virus was analyzed for neutralizing (N) and complement-requiring neutralizing (CRN) antibodies. In a usual endpoint test, N and CRN titers were 1: 40 and 1: 160, respectively, but when virus-IgG mixtures were incubated at 0 C overnight before addition of complement (C), an endpoint of 1:1280 was obtained. Virus sensitized at 0 C overnight required more C for inactivation than did sensitized virus formed earlier. Sensitization kinetic curve experiments employing a proper initial virus concentration, which permitted differentiation of sensitized viruses requiring different amounts of C, indicated that formation of sensitized virus detectable only with a relatively large amount of C proceeded slowly at IgG dilutions where the ordinary CRN antibody requiring a smaller amount of C was negligible. The results strongly suggested that the IgG sample contained slow-reacting CRN (s-CRN) antibody in excess of the hitherto known CRN antibody. As to the mechanism of formation of s-CRN complexes, experiments failed to prove the occurrence of complexes initially insensitive to C, and it appears more likely that s-CRN antibody has a comparatively low avidity for virus.", "contents": "Studies on the neutralization of herpes simplex virus. X. Demonstration of complement-requiring neutralizing (CRN) and slow-reacting CRN (s-CRN) antibodies in late IgG. A sample of late IgG from a rabbit hyperimmunized with herpes simplex virus was analyzed for neutralizing (N) and complement-requiring neutralizing (CRN) antibodies. In a usual endpoint test, N and CRN titers were 1: 40 and 1: 160, respectively, but when virus-IgG mixtures were incubated at 0 C overnight before addition of complement (C), an endpoint of 1:1280 was obtained. Virus sensitized at 0 C overnight required more C for inactivation than did sensitized virus formed earlier. Sensitization kinetic curve experiments employing a proper initial virus concentration, which permitted differentiation of sensitized viruses requiring different amounts of C, indicated that formation of sensitized virus detectable only with a relatively large amount of C proceeded slowly at IgG dilutions where the ordinary CRN antibody requiring a smaller amount of C was negligible. The results strongly suggested that the IgG sample contained slow-reacting CRN (s-CRN) antibody in excess of the hitherto known CRN antibody. As to the mechanism of formation of s-CRN complexes, experiments failed to prove the occurrence of complexes initially insensitive to C, and it appears more likely that s-CRN antibody has a comparatively low avidity for virus."}
{"id": "PMID:229390", "title": "Is prolactin involved in sperm capacitation?", "content": "Immunoreactive prolactin in high concentration was detected in the human semen. Therefore, the effect of prolactin on the various metabolic parameters of the human spermatozoa was studied. It was found that prolactin brought about many of the biochemical changes in the spermatozoa which are known to be associated with the process of capacitation. These results suggest that prolactin has a role in the sperm capacitation.", "contents": "Is prolactin involved in sperm capacitation? Immunoreactive prolactin in high concentration was detected in the human semen. Therefore, the effect of prolactin on the various metabolic parameters of the human spermatozoa was studied. It was found that prolactin brought about many of the biochemical changes in the spermatozoa which are known to be associated with the process of capacitation. These results suggest that prolactin has a role in the sperm capacitation."}
{"id": "PMID:229391", "title": "Rotavirus and coronavirus-like particles in aboriginal and non-aboriginal neonates in Kalgoorlie and Alice Springs.", "content": "In a series of six-month surveys carried out in Kalgoorlie and Alice Springs Hospitals, rotavirus was infrequently detected both in Aboriginal and in non-Aboriginal neonates. Coronavirus-like particles were also detected infrequently, but they were found more often in Aboriginal than in non-Aboriginal neonates. The surveys did not detect any 28-nm virus-like particles.", "contents": "Rotavirus and coronavirus-like particles in aboriginal and non-aboriginal neonates in Kalgoorlie and Alice Springs. In a series of six-month surveys carried out in Kalgoorlie and Alice Springs Hospitals, rotavirus was infrequently detected both in Aboriginal and in non-Aboriginal neonates. Coronavirus-like particles were also detected infrequently, but they were found more often in Aboriginal than in non-Aboriginal neonates. The surveys did not detect any 28-nm virus-like particles."}
{"id": "PMID:229405", "title": "Reconstruction of rat skeletal muscle glycerophosphate shuttle.", "content": "The activity of alpha-glycerophosphate shuttle in homogenate and in a reconstructed system (isolated mitochondria and cytoplasm) from rat skeletal muscle is presented. The influence of some inhibitors of mitochondrial alpha-glycerosphate dehydrogenase on the activity alpha-glycerophosphate shuttle is demonstrated. The possible operativity of alpha-glycerophosphate shuttle in skeletal muscle in vivo is discussed.", "contents": "Reconstruction of rat skeletal muscle glycerophosphate shuttle. The activity of alpha-glycerophosphate shuttle in homogenate and in a reconstructed system (isolated mitochondria and cytoplasm) from rat skeletal muscle is presented. The influence of some inhibitors of mitochondrial alpha-glycerosphate dehydrogenase on the activity alpha-glycerophosphate shuttle is demonstrated. The possible operativity of alpha-glycerophosphate shuttle in skeletal muscle in vivo is discussed."}
{"id": "PMID:229404", "title": "Multiple forms of inducible drug-metabolizing enzymes: a reasonable mechanism by which any organism can cope with adversity.", "content": "All organisms possess a number of genetically regulated mechanisms in order to cope with rapid adverse changes in the environment. The two systems which appear to respond to a seemingly endless array of chemical specificities are the immune response and the induction of drug-metabolizing enzymes. Similarities and differences between the immunoglobulin and the cytochrome P-450-mediated monooxygenase systems are described. DNA insertion sequences, plasmid \"transposons,\" maize \"controlling elements,\" gene duplication, intervening sequences, and high-frequency intergenic recombination are all discussed as possible methods by which organisms can \"adapt\" quickly to a new selective pressure. If the regulation of P-450 induction resembles in any way the other methods by which pro- and eukaryotes cope genetically with numerous forms of environmental adversity, therefore, it is very likely that mammalian tissues contain hundreds, if not thousands, of inducible forms of P-450.", "contents": "Multiple forms of inducible drug-metabolizing enzymes: a reasonable mechanism by which any organism can cope with adversity. All organisms possess a number of genetically regulated mechanisms in order to cope with rapid adverse changes in the environment. The two systems which appear to respond to a seemingly endless array of chemical specificities are the immune response and the induction of drug-metabolizing enzymes. Similarities and differences between the immunoglobulin and the cytochrome P-450-mediated monooxygenase systems are described. DNA insertion sequences, plasmid \"transposons,\" maize \"controlling elements,\" gene duplication, intervening sequences, and high-frequency intergenic recombination are all discussed as possible methods by which organisms can \"adapt\" quickly to a new selective pressure. If the regulation of P-450 induction resembles in any way the other methods by which pro- and eukaryotes cope genetically with numerous forms of environmental adversity, therefore, it is very likely that mammalian tissues contain hundreds, if not thousands, of inducible forms of P-450."}
{"id": "PMID:229409", "title": "[The diagnosis of amebic liver abscesses. A study of 107 cases (author's transl)].", "content": "We have investigated the serum antibodies of 107 patients with extra-intestinal amebiasis and 72 control subjects without demonstrable infection with E. histolytica. It was shown that by means of countercurrent immuno-electrophoresis and indirect hemagglutination scintigraphy and taking into consideration the clinical picture, the diagnosis of extraintestinal amebiasis can be made with the necessary high degree of probability.", "contents": "[The diagnosis of amebic liver abscesses. A study of 107 cases (author's transl)]. We have investigated the serum antibodies of 107 patients with extra-intestinal amebiasis and 72 control subjects without demonstrable infection with E. histolytica. It was shown that by means of countercurrent immuno-electrophoresis and indirect hemagglutination scintigraphy and taking into consideration the clinical picture, the diagnosis of extraintestinal amebiasis can be made with the necessary high degree of probability."}
{"id": "PMID:229407", "title": "The regulation of cell proliferation by calcium and cyclic AMP.", "content": "Calcium, in partnership with cyclic AMP, controls the proliferation of non-tumorigenic cells in vitro and in vivo. While it does not seem to be involved in the proliferative activation of cells such as hepatocytes (in vivo) or small lymphocytes (in vitro), it does control two later stages of prereplicative (G1) development. It must be one of the very many regulatory and permissive factors affecting early prereplicative development, because severe calcium deprivation reversibly arrests some types of cell early in the G1 phase of their growth-division cycle in vitro. However, calcium more specifically and much more often regulates a later (mid or late G1) stage of prereplicative development. Thus, regardless of its severity or the type of cell, calcium deprivation in vitro or in vivo reversibly stops proliferative development at that part of the G1 phase in which the cellular cyclic AMP content transiently rises and the synthesis of the four deoxyribonucleotides begins. The evidence points to calcium and the cyclic AMP surge being co-generators of the signal committing the cell to DNA synthesis. The evidence is best explained so far by the cyclic AMP surge causing a surge of calcium ions which combine with molecules of the multi-purpose, calcium-dependent, regulator protein calmodulin (CDR) somewhere between the cell surface and the cytosol. The resulting Ca-calmodulin complexes then stimulate many different (and possibly membrane-associated) enzymes such as protein kinases, one of which produces the DNA-synthetic initiator. Calcium has little or no influence on the proliferation of tumor cells. Some possible explanations of this very important loss of control are considered.", "contents": "The regulation of cell proliferation by calcium and cyclic AMP. Calcium, in partnership with cyclic AMP, controls the proliferation of non-tumorigenic cells in vitro and in vivo. While it does not seem to be involved in the proliferative activation of cells such as hepatocytes (in vivo) or small lymphocytes (in vitro), it does control two later stages of prereplicative (G1) development. It must be one of the very many regulatory and permissive factors affecting early prereplicative development, because severe calcium deprivation reversibly arrests some types of cell early in the G1 phase of their growth-division cycle in vitro. However, calcium more specifically and much more often regulates a later (mid or late G1) stage of prereplicative development. Thus, regardless of its severity or the type of cell, calcium deprivation in vitro or in vivo reversibly stops proliferative development at that part of the G1 phase in which the cellular cyclic AMP content transiently rises and the synthesis of the four deoxyribonucleotides begins. The evidence points to calcium and the cyclic AMP surge being co-generators of the signal committing the cell to DNA synthesis. The evidence is best explained so far by the cyclic AMP surge causing a surge of calcium ions which combine with molecules of the multi-purpose, calcium-dependent, regulator protein calmodulin (CDR) somewhere between the cell surface and the cytosol. The resulting Ca-calmodulin complexes then stimulate many different (and possibly membrane-associated) enzymes such as protein kinases, one of which produces the DNA-synthetic initiator. Calcium has little or no influence on the proliferation of tumor cells. Some possible explanations of this very important loss of control are considered."}
{"id": "PMID:229410", "title": "The wavelength dependence of 8-methoxypsoralen photosensitization of radiation-enchanced reactivation in a mammalian cell-virus system.", "content": "The combined effect of 8-methoxypsoralen (8-MOP) and ultraviolet (UV) radiation on the ability of an irradiated mammalian cell (CV-1) to reactivate UV-irradiated mammalian virus (Herpes simplex) was tested. Prior treatment of cells with 8-MOP was found to increase Radiation-Enhanced Reactivation (RER) at one wavelength (297 nm) in the far ultraviolet but not at others (240-289 nm). This same treatment induced RER in the near UV (302-370 nm) and the visible region (380-400 nm). An action spectrum for the photo-sensitized induction of this cellular parameter was obtained. This action spectrum is consistent with the absorption spectrum for 8-MOP and the theory that damage to DNA is, at least in part, responsible for Radiation-Enhanced Reactivation.", "contents": "The wavelength dependence of 8-methoxypsoralen photosensitization of radiation-enchanced reactivation in a mammalian cell-virus system. The combined effect of 8-methoxypsoralen (8-MOP) and ultraviolet (UV) radiation on the ability of an irradiated mammalian cell (CV-1) to reactivate UV-irradiated mammalian virus (Herpes simplex) was tested. Prior treatment of cells with 8-MOP was found to increase Radiation-Enhanced Reactivation (RER) at one wavelength (297 nm) in the far ultraviolet but not at others (240-289 nm). This same treatment induced RER in the near UV (302-370 nm) and the visible region (380-400 nm). An action spectrum for the photo-sensitized induction of this cellular parameter was obtained. This action spectrum is consistent with the absorption spectrum for 8-MOP and the theory that damage to DNA is, at least in part, responsible for Radiation-Enhanced Reactivation."}
{"id": "PMID:229411", "title": "An effect of cell-culture passage on ultraviolet-enhanced viral reactivation by mammalian cells.", "content": "The ability of ultraviolet-irradiated African green monkey kidney cells to reactivate UV-damaged herpes simplex virus was tested over a range of 57 passages (24-81). Several types of controls were employed to minimize daily variations. The results indicate that in this system cells demonstrate an increasing efficiency to reactivate UV-damaged virus until approx. passage 60, followed by a decrease in this ability beyond this passage. Chromosome counts at selected passages revealed no significant change in chromosome number as a function of passage. The mechanism(s) or factor(s) causing this effect are unknown.", "contents": "An effect of cell-culture passage on ultraviolet-enhanced viral reactivation by mammalian cells. The ability of ultraviolet-irradiated African green monkey kidney cells to reactivate UV-damaged herpes simplex virus was tested over a range of 57 passages (24-81). Several types of controls were employed to minimize daily variations. The results indicate that in this system cells demonstrate an increasing efficiency to reactivate UV-damaged virus until approx. passage 60, followed by a decrease in this ability beyond this passage. Chromosome counts at selected passages revealed no significant change in chromosome number as a function of passage. The mechanism(s) or factor(s) causing this effect are unknown."}
{"id": "PMID:229415", "title": "Splicing of the late mRNAs of polyoma virus does not occur in the cytoplasm of the infected cell.", "content": "The three mRNAs that encode the capsid proteins of polyoma virus are produced by the excision of different sequences from continuous transcripts of the L strand of viral DNA. All three of the mRNAs have long half lives, and the larger species are not converted to the smaller ones to any measurable extent within the cytoplasm. Therefore the cytoplasmic proportions of late polyoma mRNAs are predetermined by splicing that is confined to the nucleus of the infected cell and which is complete by the time that mRNA is transported to the cytoplasm.", "contents": "Splicing of the late mRNAs of polyoma virus does not occur in the cytoplasm of the infected cell. The three mRNAs that encode the capsid proteins of polyoma virus are produced by the excision of different sequences from continuous transcripts of the L strand of viral DNA. All three of the mRNAs have long half lives, and the larger species are not converted to the smaller ones to any measurable extent within the cytoplasm. Therefore the cytoplasmic proportions of late polyoma mRNAs are predetermined by splicing that is confined to the nucleus of the infected cell and which is complete by the time that mRNA is transported to the cytoplasm."}
{"id": "PMID:229417", "title": "Simultaneous ultrastructural demonstration of multiple peptides in endocrine cells by a novel immunocytochemical method.", "content": "Current immunocytochemical techniques detect all antibodies that react with tissue. Unfortunately, some of these antibodies may react with antigens other than those intended. Such problems are minimised by using sets of antibodies detecting different regions of the desired antigen. However, as immunocytochemical methods can now detect very low antibody concentrations, the purity of antisera is critical. Furthermore, although antisers may be purified by affinity chromatography, difficulties in recovering high-avidity antibodies cause most affinity-purified antisera to be enriched in low-avidity antibodies, which may be dislodged during staining. We have therefore developed, and describe here, a new ultrastructural post-embedding staining technique, based on the divalency of IgG molecules and using antigen-coated colloidal gold granules. Previously, colloidal gold-labelled antibodies have been used for post-embedding staining. Unlike our gold-labelled antigen detection (GLAD) technique, however, these methods do not differentiate between specific and nonspecific antibodies. The GLAD method detects only specific antibodies and does not select against high-avidity antibodies, and in this it resembles the radioimmunocytochemical method. However, the GLAD method differs from the latter in that it is useful for ultrastructural studies, does not require autoradiography and allows simultaneous detection of multiple antigens. Moreover, specific activity compared with background may be quantitated.", "contents": "Simultaneous ultrastructural demonstration of multiple peptides in endocrine cells by a novel immunocytochemical method. Current immunocytochemical techniques detect all antibodies that react with tissue. Unfortunately, some of these antibodies may react with antigens other than those intended. Such problems are minimised by using sets of antibodies detecting different regions of the desired antigen. However, as immunocytochemical methods can now detect very low antibody concentrations, the purity of antisera is critical. Furthermore, although antisers may be purified by affinity chromatography, difficulties in recovering high-avidity antibodies cause most affinity-purified antisera to be enriched in low-avidity antibodies, which may be dislodged during staining. We have therefore developed, and describe here, a new ultrastructural post-embedding staining technique, based on the divalency of IgG molecules and using antigen-coated colloidal gold granules. Previously, colloidal gold-labelled antibodies have been used for post-embedding staining. Unlike our gold-labelled antigen detection (GLAD) technique, however, these methods do not differentiate between specific and nonspecific antibodies. The GLAD method detects only specific antibodies and does not select against high-avidity antibodies, and in this it resembles the radioimmunocytochemical method. However, the GLAD method differs from the latter in that it is useful for ultrastructural studies, does not require autoradiography and allows simultaneous detection of multiple antigens. Moreover, specific activity compared with background may be quantitated."}
{"id": "PMID:229418", "title": "Regulation of glutamate receptors by cations.", "content": "Current evidence suggests that glutamate is a major excitatory neurotransmitter in the mammalian central nervous system (CNS); particularly, glutamate excites most neurones in the CNS. Until recently this effect was widely used to study glutamate receptors and to distinguish them from those of other excitatory amino acids. The development of ligand binding studies for many neurotransmitters has facilitated the study of receptors at the molecular level and using these methods we recently reported the existence in hippocampal membranes of pharmacologically distinct sodium-dependent and sodium-independent glutamate binding sites, the former related to high-affinity uptake and the latter exhibiting several characteristics of postsynaptic receptor sites. We now report that, as with other neurotransmitters, several ions regulate the Na-independent binding of glutamate; the monovalent cations induce a decreased binding while certain divalent cations enhance this Na-independent binding. Additionally, since some of these effects appear to be irreversible, we propose that the regulation of glutamate binding by cations might account for the extremely long-lasting potentiation of synaptic responses found in the hippocampus following bursts of repetitive electrical stimulation (see ref. 9 for a review).", "contents": "Regulation of glutamate receptors by cations. Current evidence suggests that glutamate is a major excitatory neurotransmitter in the mammalian central nervous system (CNS); particularly, glutamate excites most neurones in the CNS. Until recently this effect was widely used to study glutamate receptors and to distinguish them from those of other excitatory amino acids. The development of ligand binding studies for many neurotransmitters has facilitated the study of receptors at the molecular level and using these methods we recently reported the existence in hippocampal membranes of pharmacologically distinct sodium-dependent and sodium-independent glutamate binding sites, the former related to high-affinity uptake and the latter exhibiting several characteristics of postsynaptic receptor sites. We now report that, as with other neurotransmitters, several ions regulate the Na-independent binding of glutamate; the monovalent cations induce a decreased binding while certain divalent cations enhance this Na-independent binding. Additionally, since some of these effects appear to be irreversible, we propose that the regulation of glutamate binding by cations might account for the extremely long-lasting potentiation of synaptic responses found in the hippocampus following bursts of repetitive electrical stimulation (see ref. 9 for a review)."}
{"id": "PMID:229419", "title": "Mutant avian erythroblastosis virus with restricted target cell specificity.", "content": "Avian erythroblastosis virus (AEV) induces a fatal erythroblastosis within 2 weeks of intravenous injection in chicks in virtually 100% of cases. In chicks injected intramuscularly, sarcomas frequently develop at the site of injection before the animals die from erythroblastosis. In vitro, AEV transforms both erythroblasts, derived from bone marrow cultures, and fibroblasts. These effects have been shown to be a general property of AEV and not of separate leukaemia- and sarcoma-inducing forms of the virus. AEV is defective for replication and can be propagated only in the prewence of helper virus. Its transformation specificity is independent of the helper virus used. It is not clear whether AEV has two different genes controlling transformation of the two types of target cell or whether it has only one gene coding for both. To investigate this question, we looked for mutants of AEV unable to transform one of the two types of target cell. We now describe such a mutant, which is defective for erythroblast transformation but which can still transform fibroblasts.", "contents": "Mutant avian erythroblastosis virus with restricted target cell specificity. Avian erythroblastosis virus (AEV) induces a fatal erythroblastosis within 2 weeks of intravenous injection in chicks in virtually 100% of cases. In chicks injected intramuscularly, sarcomas frequently develop at the site of injection before the animals die from erythroblastosis. In vitro, AEV transforms both erythroblasts, derived from bone marrow cultures, and fibroblasts. These effects have been shown to be a general property of AEV and not of separate leukaemia- and sarcoma-inducing forms of the virus. AEV is defective for replication and can be propagated only in the prewence of helper virus. Its transformation specificity is independent of the helper virus used. It is not clear whether AEV has two different genes controlling transformation of the two types of target cell or whether it has only one gene coding for both. To investigate this question, we looked for mutants of AEV unable to transform one of the two types of target cell. We now describe such a mutant, which is defective for erythroblast transformation but which can still transform fibroblasts."}
{"id": "PMID:229420", "title": "Isolation of a replication-defective murine leukaemia virus from cultured AKR leukaemia cells.", "content": "Mice of the AKR strain are characterised by a high incidence of spontaneous thymic lymphomas. AKR chromosomes contain the genomes of ecotropic murine leukaemia virus (MuLV) at two loci, termed Akv-1 and Akv-2 (refs 2-6). Shortly after birth, the normal tissues of AKR mice begin to produce high levels of this XC-positive MuLV (ref. 7) (that is, one that forms XC plaques). A second class of MuLV, termed mink cell focus-inducing virus (MCF), is produced specifically by preleukaemic and leukaemic AKR thymocytes. Nowinski et al. have established a series of tissue culture lines from AKR leukaemias and reported that the resulting cell lines produce virus particles, but that these particles, surprisingly, do not give rise to XC plaques. We have analysed the virus particles produced by one of these cell lines, termed AKRSL2. We show here that, unlike most or all of the nonmalignant tissues in the AKR mouse, these cultured lymphoma cells produce very little non-defective ecotropic MuLV; however, they do produce replication-defective ecotropic MuLV.", "contents": "Isolation of a replication-defective murine leukaemia virus from cultured AKR leukaemia cells. Mice of the AKR strain are characterised by a high incidence of spontaneous thymic lymphomas. AKR chromosomes contain the genomes of ecotropic murine leukaemia virus (MuLV) at two loci, termed Akv-1 and Akv-2 (refs 2-6). Shortly after birth, the normal tissues of AKR mice begin to produce high levels of this XC-positive MuLV (ref. 7) (that is, one that forms XC plaques). A second class of MuLV, termed mink cell focus-inducing virus (MCF), is produced specifically by preleukaemic and leukaemic AKR thymocytes. Nowinski et al. have established a series of tissue culture lines from AKR leukaemias and reported that the resulting cell lines produce virus particles, but that these particles, surprisingly, do not give rise to XC plaques. We have analysed the virus particles produced by one of these cell lines, termed AKRSL2. We show here that, unlike most or all of the nonmalignant tissues in the AKR mouse, these cultured lymphoma cells produce very little non-defective ecotropic MuLV; however, they do produce replication-defective ecotropic MuLV."}
{"id": "PMID:229424", "title": "Structure and sequence of the multihaem cytochrome c3.", "content": "The molecular structure of cytochrome c3 isolated from Desulfovibrio desulfuricans has been solved on the basis of its crystallographic determination at 2.5 A resolution and of an essentially complete sequence. The molecule consists of a single polypeptide chain wrapped around a very compact core of four non-parallel haems which present a relatively high degree of exposure to the solvent. Alignment of the amino acid sequences of cytochrome c3 from several species suggests that the structure reported here is characteristic of the cytochrome c3 group.", "contents": "Structure and sequence of the multihaem cytochrome c3. The molecular structure of cytochrome c3 isolated from Desulfovibrio desulfuricans has been solved on the basis of its crystallographic determination at 2.5 A resolution and of an essentially complete sequence. The molecule consists of a single polypeptide chain wrapped around a very compact core of four non-parallel haems which present a relatively high degree of exposure to the solvent. Alignment of the amino acid sequences of cytochrome c3 from several species suggests that the structure reported here is characteristic of the cytochrome c3 group."}
{"id": "PMID:229429", "title": "[Quantum analysis of postsynaptic potentials].", "content": "Basic formulations of the quantum theory for synaptic transmission are listed. Methods for determining the mean quantum content, quantum value and binomial parameters describing the amplitude distributions of the unitary and \"minimal\" postsynaptic potentials are discussed. Literature and author's determinations of the quantum parameters for the synapses of the central nervous system are described. The comparison is made with similar determinations for more studied peripheral junctions. Some difficulties and perspective of the quantum theory are discussed.", "contents": "[Quantum analysis of postsynaptic potentials]. Basic formulations of the quantum theory for synaptic transmission are listed. Methods for determining the mean quantum content, quantum value and binomial parameters describing the amplitude distributions of the unitary and \"minimal\" postsynaptic potentials are discussed. Literature and author's determinations of the quantum parameters for the synapses of the central nervous system are described. The comparison is made with similar determinations for more studied peripheral junctions. Some difficulties and perspective of the quantum theory are discussed."}
{"id": "PMID:229430", "title": "[Electrophysiologic study of conduction of afferent impulses through the medial geniculate body].", "content": "In experiments carried out on cats immobilzed with d-tubocurarine 280 neurons located in pars principalis of the medial geniculate body and 408 auditory cortical neurons located in AI were studied extra- and intracellularly in response to stimulation of the brachium of the inferior colliculus and geniculocortical fibres. It was shown that the initial stage of the reaction observed in the medial geniculate body neurons response to stimulation of the brachium of the inferior colliculus continue for 13.0 ms. Excitation of 72% of neurons participating in the reaction occurs during the first 3 ms after stimulation. 84% of IPSPs arouse in the same period of time. It is found that some medial geniculate neurons have axons entering the inferior colliculus. Substantial part of fibres in the brachium of the inferior colliculus comes to the auditory cortex without synaptic switching in the medial geniculate body. 76% of medial geniculate neurons from the group excited monosynaptically are thalamocortical relay neurons and the rest are interneurons. 90% of relay neurons in the medial geniculate body are excited monosynaptically. Many medial geniculate neurons respond to stimulation of the brachium of the interior colliculus by EPSP-IPSP sequence or by primary IPSPs. About 20% of primary IPSPs develop monosynaptically. The maximal amount of IPSPs comes into being disynaptically with the participation of inhibitory interneuron located at the input to the medial geniculate body. The inhibition observed in this case is direct afferent one.", "contents": "[Electrophysiologic study of conduction of afferent impulses through the medial geniculate body]. In experiments carried out on cats immobilzed with d-tubocurarine 280 neurons located in pars principalis of the medial geniculate body and 408 auditory cortical neurons located in AI were studied extra- and intracellularly in response to stimulation of the brachium of the inferior colliculus and geniculocortical fibres. It was shown that the initial stage of the reaction observed in the medial geniculate body neurons response to stimulation of the brachium of the inferior colliculus continue for 13.0 ms. Excitation of 72% of neurons participating in the reaction occurs during the first 3 ms after stimulation. 84% of IPSPs arouse in the same period of time. It is found that some medial geniculate neurons have axons entering the inferior colliculus. Substantial part of fibres in the brachium of the inferior colliculus comes to the auditory cortex without synaptic switching in the medial geniculate body. 76% of medial geniculate neurons from the group excited monosynaptically are thalamocortical relay neurons and the rest are interneurons. 90% of relay neurons in the medial geniculate body are excited monosynaptically. Many medial geniculate neurons respond to stimulation of the brachium of the interior colliculus by EPSP-IPSP sequence or by primary IPSPs. About 20% of primary IPSPs develop monosynaptically. The maximal amount of IPSPs comes into being disynaptically with the participation of inhibitory interneuron located at the input to the medial geniculate body. The inhibition observed in this case is direct afferent one."}
{"id": "PMID:229426", "title": "How the size of motoneurones determines their susceptibility to discharge.", "content": "The susceptibility of motoneurones to discharge by physiological inputs varies inversely with their size. This relationship has far-reaching consequences for the control of muscular tension, and also accounts for significant differences in the properties of muscle fibres and motor units. The probable basis for the relationship is that the amplitude of excitatory postsynaptic potentials (e.p.s.ps) is also correlated inversely with cell size, but no satisfactory explanation for this finding is known. We now describe experiments which indicate that afferent impulses invade the relatively simple ramifications of fibres going to small motoneurones more completely than the extensive arborisations going to large cells. This results in activation of a higher percentage of the synaptic endings on small cells, which produces larger e.p.s.ps in them and accounts for their greater susceptibility to discharge.", "contents": "How the size of motoneurones determines their susceptibility to discharge. The susceptibility of motoneurones to discharge by physiological inputs varies inversely with their size. This relationship has far-reaching consequences for the control of muscular tension, and also accounts for significant differences in the properties of muscle fibres and motor units. The probable basis for the relationship is that the amplitude of excitatory postsynaptic potentials (e.p.s.ps) is also correlated inversely with cell size, but no satisfactory explanation for this finding is known. We now describe experiments which indicate that afferent impulses invade the relatively simple ramifications of fibres going to small motoneurones more completely than the extensive arborisations going to large cells. This results in activation of a higher percentage of the synaptic endings on small cells, which produces larger e.p.s.ps in them and accounts for their greater susceptibility to discharge."}
{"id": "PMID:229431", "title": "[Heterosynaptic interactions in fields CA1 and CA3 of the hippocampus in vitro].", "content": "Heterosynaptic interactions between the perforant path and Schaffer's collaterals in the field CA1 and between the perforant path and dentate mossy fibres in the field CA3 were investigated in guinea pig hippocampal slices. Using the method of paired stimuli, space-time summation (for 20--50 ms) was observed in both systems with stimuli sub-threshold for spike generation. Spike responses of the neurons to testing stimulation of afferents synapsing upon the terminal parts of apical dendrites (perforant path) were depressed after spike discharge to conditioning stimulation of proximal afferents (for about 20 ms in CA1, and for about 300 ms in CA3). With inverse combination of the stimuli the period of suppression was much shorter (3--8 ms). Tetanization of the mossy fibres was followed by prolonged (2--30 min) depression of the CA3 responses to the perforant path stimulation. No other reliable long-lasting posttetanic heterosynaptic effects were observed.", "contents": "[Heterosynaptic interactions in fields CA1 and CA3 of the hippocampus in vitro]. Heterosynaptic interactions between the perforant path and Schaffer's collaterals in the field CA1 and between the perforant path and dentate mossy fibres in the field CA3 were investigated in guinea pig hippocampal slices. Using the method of paired stimuli, space-time summation (for 20--50 ms) was observed in both systems with stimuli sub-threshold for spike generation. Spike responses of the neurons to testing stimulation of afferents synapsing upon the terminal parts of apical dendrites (perforant path) were depressed after spike discharge to conditioning stimulation of proximal afferents (for about 20 ms in CA1, and for about 300 ms in CA3). With inverse combination of the stimuli the period of suppression was much shorter (3--8 ms). Tetanization of the mossy fibres was followed by prolonged (2--30 min) depression of the CA3 responses to the perforant path stimulation. No other reliable long-lasting posttetanic heterosynaptic effects were observed."}
{"id": "PMID:229432", "title": "[Responses of the vibrissal projection zone of the cat somatosensory projection zone to afferent activation].", "content": "Responses of 375 neurons of SI cortex region in the vibrissae projection zone were recorded in unanesthetized cats: responses to electrical stimulation of infraorbital nerve and mechanical stimulation of vibrissae were studied. Nerve and vibrissae stimulation evoked complex synaptic potentials (short EPSPs followed by IPSPs) in most neurons primary IPSPs were found in other units. The corresponding changes of impulse activity could be recorded in many neurons extracellularly. Initial inhibition was evoked by vibrissae stimulation more frequently (in 45% units comparing to 16% when the nerve was stimulated). Difference of minimal EPSP and IPSP latencies during intraorbital nerve stimulation was 0.8 ms, difference of mean values--1.4 ms. Directional sensitivity of cortical neurons (to the changes in direction of vibrissae deflection) is demonstrated. Neurons located in the close proximity may possess different pattern of directional sensitivity. It is supposed that short latency neuronal inhibition in SI cortical zone is mainly afferent (not recurrent). Probable mechanisms of directional sensitivity of the studied neurons are discussed.", "contents": "[Responses of the vibrissal projection zone of the cat somatosensory projection zone to afferent activation]. Responses of 375 neurons of SI cortex region in the vibrissae projection zone were recorded in unanesthetized cats: responses to electrical stimulation of infraorbital nerve and mechanical stimulation of vibrissae were studied. Nerve and vibrissae stimulation evoked complex synaptic potentials (short EPSPs followed by IPSPs) in most neurons primary IPSPs were found in other units. The corresponding changes of impulse activity could be recorded in many neurons extracellularly. Initial inhibition was evoked by vibrissae stimulation more frequently (in 45% units comparing to 16% when the nerve was stimulated). Difference of minimal EPSP and IPSP latencies during intraorbital nerve stimulation was 0.8 ms, difference of mean values--1.4 ms. Directional sensitivity of cortical neurons (to the changes in direction of vibrissae deflection) is demonstrated. Neurons located in the close proximity may possess different pattern of directional sensitivity. It is supposed that short latency neuronal inhibition in SI cortical zone is mainly afferent (not recurrent). Probable mechanisms of directional sensitivity of the studied neurons are discussed."}
{"id": "PMID:229433", "title": "Familial gliomas.", "content": "The authors report two pairs of siblings who had intracranial malignant gliomas. Genetic influences in the occurence of gliomas are discussed.", "contents": "Familial gliomas. The authors report two pairs of siblings who had intracranial malignant gliomas. Genetic influences in the occurence of gliomas are discussed."}
{"id": "PMID:229436", "title": "Effect of hippocampus extirpation in the rat on glutamate levels in target structures of hippocampal efferents.", "content": "Twenty days after complete uni- or bilateral hippocampus extirpation in rats, a 25% decrease in glutamate concentration was observed in the septum. Glutamate content also decreased in other terminal structures of the hippocampo-subicular system, i.e. entorhinal cortex, nucleus accumbens septi, mammillary bodies and contralateral hippocampus. It is concluded that the fall in glutamate content which is absent in caudate nucleus is specific for target regions of the hippocampal efferents, adding further support to the suggested transmitter role of glutamate in the limbic system.", "contents": "Effect of hippocampus extirpation in the rat on glutamate levels in target structures of hippocampal efferents. Twenty days after complete uni- or bilateral hippocampus extirpation in rats, a 25% decrease in glutamate concentration was observed in the septum. Glutamate content also decreased in other terminal structures of the hippocampo-subicular system, i.e. entorhinal cortex, nucleus accumbens septi, mammillary bodies and contralateral hippocampus. It is concluded that the fall in glutamate content which is absent in caudate nucleus is specific for target regions of the hippocampal efferents, adding further support to the suggested transmitter role of glutamate in the limbic system."}
{"id": "PMID:229437", "title": "Differentiation between anti- and orthodromic responses to nerve stimulation in neurons with axo-axonal synapses (Helix pomatia).", "content": "In identified neurons of Helix pomatia nerve stimulation evoked depolarizations of short latencies. The mechanisms underlying these potentials were studied by conventional electrophysiological and intracellular staining techniques. Most of the depolarizations behaved like chemically mediated postsynaptic potentials. The remaining responses can be regarded either as antidromic axonal action potentials (APs) or as electrotonic junction potentials. The differentiation between the latter alternatives and hence the identification of the axonal pathways of the impaled neurons proved to be difficult using conventional methods.", "contents": "Differentiation between anti- and orthodromic responses to nerve stimulation in neurons with axo-axonal synapses (Helix pomatia). In identified neurons of Helix pomatia nerve stimulation evoked depolarizations of short latencies. The mechanisms underlying these potentials were studied by conventional electrophysiological and intracellular staining techniques. Most of the depolarizations behaved like chemically mediated postsynaptic potentials. The remaining responses can be regarded either as antidromic axonal action potentials (APs) or as electrotonic junction potentials. The differentiation between the latter alternatives and hence the identification of the axonal pathways of the impaled neurons proved to be difficult using conventional methods."}
{"id": "PMID:229438", "title": "The opiate antagonist, naloxone, does not affect descending inhibition from midbrain of nociceptive spinal neuronal discharges in the cat.", "content": "Discharges were recorded from spinal dorsal horn neurons in response to noxious skin heating (e.g. 50 degrees C). Repetitive electrical stimulation of the mesencephalic periaqueductal gray (PAG) inhibited these nociceptive discharges. In each of 9 experiments systemic administration of naloxone (1-3 mg/kg) did not affect this descending inhibition, arguing against involvement of endogenous opiates.", "contents": "The opiate antagonist, naloxone, does not affect descending inhibition from midbrain of nociceptive spinal neuronal discharges in the cat. Discharges were recorded from spinal dorsal horn neurons in response to noxious skin heating (e.g. 50 degrees C). Repetitive electrical stimulation of the mesencephalic periaqueductal gray (PAG) inhibited these nociceptive discharges. In each of 9 experiments systemic administration of naloxone (1-3 mg/kg) did not affect this descending inhibition, arguing against involvement of endogenous opiates."}
{"id": "PMID:229439", "title": "Regional distribution of a high-affinity enkephalin-degrading peptidase ('enkephalinase') and effects of lesions suggest localization in the vicinity of opiate receptors in brain.", "content": "The distribution of a high affinity enkephalin-dipeptidylcarboxypeptidase between regions of mouse brain is markedly heterogenous and parallels that of opiate receptors. Furthermore intrastriatal administration of kainic acid as well as interruption of the nigrostriatal dopaminergic pathway by 6-hydroxydopamine (6-OHDA) lead to similar decreases in this peptidase activity and in the number of opiate receptors. On the contrary, no correlation was found between low affinity enkephalin degrading enzymes and opiate receptors.", "contents": "Regional distribution of a high-affinity enkephalin-degrading peptidase ('enkephalinase') and effects of lesions suggest localization in the vicinity of opiate receptors in brain. The distribution of a high affinity enkephalin-dipeptidylcarboxypeptidase between regions of mouse brain is markedly heterogenous and parallels that of opiate receptors. Furthermore intrastriatal administration of kainic acid as well as interruption of the nigrostriatal dopaminergic pathway by 6-hydroxydopamine (6-OHDA) lead to similar decreases in this peptidase activity and in the number of opiate receptors. On the contrary, no correlation was found between low affinity enkephalin degrading enzymes and opiate receptors."}
{"id": "PMID:229440", "title": "L-glutamate specific [3H]kainic acid binding in the rat neostriatum after degeneration of the cortico-striatal pathway.", "content": "Four weeks after lesion of the cortico-striatal pathway, the specific kainic acid binding was reduced by 20% in the neostriatum. It is concluded that the binding sites are most likely not located on cortico-striatal neurons. The displacement of kainic acid by some chemical indicates that the kainic acid binding site is different from the glutamate binding site, as defined iontophoretically.", "contents": "L-glutamate specific [3H]kainic acid binding in the rat neostriatum after degeneration of the cortico-striatal pathway. Four weeks after lesion of the cortico-striatal pathway, the specific kainic acid binding was reduced by 20% in the neostriatum. It is concluded that the binding sites are most likely not located on cortico-striatal neurons. The displacement of kainic acid by some chemical indicates that the kainic acid binding site is different from the glutamate binding site, as defined iontophoretically."}
{"id": "PMID:229441", "title": "An epidemic of gastroenteritis in Auckland 1978.", "content": "During an epidemic of gastroenteritis which spread throughout New Zealand in 1978, 372 cases of nonbacterial illness were documented in children in Auckland during the months of June and July. A brief account is given of the clinical picture observed. Evidence from virological techniques suggests that some if not all cases were due to rotavirus. The severity of illness may have been greater than most observers to date have noted. From our observations we raise the possibility of air-borne spread, perhaps in addition to faecal-oral. We wish to emphasise that drugs play no part in the treatment of viral gastroenteritis, that home-made electrolyte solutions can be hazardous and that early intravenous therapy can be life-saving.", "contents": "An epidemic of gastroenteritis in Auckland 1978. During an epidemic of gastroenteritis which spread throughout New Zealand in 1978, 372 cases of nonbacterial illness were documented in children in Auckland during the months of June and July. A brief account is given of the clinical picture observed. Evidence from virological techniques suggests that some if not all cases were due to rotavirus. The severity of illness may have been greater than most observers to date have noted. From our observations we raise the possibility of air-borne spread, perhaps in addition to faecal-oral. We wish to emphasise that drugs play no part in the treatment of viral gastroenteritis, that home-made electrolyte solutions can be hazardous and that early intravenous therapy can be life-saving."}
{"id": "PMID:229442", "title": "Two strains of human rotavirus in Auckland.", "content": "Polyacrylamide gel electrophoresis of human rotavirus RNA has identified at least two distinct strains of virus currently circulating in Auckland. The sensitivity of the method both for detecting rotavirus infection and for identifying variation in rotavirus strains is discussed.", "contents": "Two strains of human rotavirus in Auckland. Polyacrylamide gel electrophoresis of human rotavirus RNA has identified at least two distinct strains of virus currently circulating in Auckland. The sensitivity of the method both for detecting rotavirus infection and for identifying variation in rotavirus strains is discussed."}
{"id": "PMID:229448", "title": "Methotrexate with citrovorum factor rescue for nonmetastatic gestational trophoblastic neoplasms.", "content": "Fifty-one patients with nonmetastatic gestational trophoblastic neoplasms (NMGTN) were treated with either 4 or 6 mg/kg methotrexate (MTX) and citrovorum factor (CF) rescue to determine if the higher dosage could reduce the number of courses of chemotherapy required to achieve remission. Thirty-six of 41 patients treated with 4 mg/kg MTX achieved complete remission with 1 course of chemotherapy. Increasing the initial dose of MTX to 6 mg/kg in 10 patients did not reduce the need for subsequent courses of chemotherapy but did increase associated toxicity. The rate of fall in the human chorionic gonadotropin (hCG) titer following the initial course of MTX-CF was found to be an accurate predictor of therapeutic response. The need for further chemotherapy may be anticipated if the hCG titer has not fallen by 1 log within 18 days.", "contents": "Methotrexate with citrovorum factor rescue for nonmetastatic gestational trophoblastic neoplasms. Fifty-one patients with nonmetastatic gestational trophoblastic neoplasms (NMGTN) were treated with either 4 or 6 mg/kg methotrexate (MTX) and citrovorum factor (CF) rescue to determine if the higher dosage could reduce the number of courses of chemotherapy required to achieve remission. Thirty-six of 41 patients treated with 4 mg/kg MTX achieved complete remission with 1 course of chemotherapy. Increasing the initial dose of MTX to 6 mg/kg in 10 patients did not reduce the need for subsequent courses of chemotherapy but did increase associated toxicity. The rate of fall in the human chorionic gonadotropin (hCG) titer following the initial course of MTX-CF was found to be an accurate predictor of therapeutic response. The need for further chemotherapy may be anticipated if the hCG titer has not fallen by 1 log within 18 days."}
{"id": "PMID:229449", "title": "Endocrine and androgen-receptor studies in a patient with XY gonadal agenesis.", "content": "A 19-year-old phenotypic female with gonadal agenesis and XY karyotype underwent an endocrinologic study. She lacked secondary sexual characteristics and there was posterior labial fusion, absence of vagina, and no gonadal or gonadal duct tissues present at laparotomy. Elevated levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) responded well to intravenous injection of LH-releasing hormone (LH-RH) but did not respond to clomiphene citrate. Both OH and FSH levels were suppressed by administration of testosterone or estrogen. Low serum concentration of testosterone did not respond to human chorionic gonadotropin (hCG) injection. Dihydrotestosterone binding by cultured skin fibroblast revealed the existence of a binding component with low capacity and high affinity. This is the first report of a patient with XY gonadal agenesis in whom androgen receptors in the target cells are demonstrated.", "contents": "Endocrine and androgen-receptor studies in a patient with XY gonadal agenesis. A 19-year-old phenotypic female with gonadal agenesis and XY karyotype underwent an endocrinologic study. She lacked secondary sexual characteristics and there was posterior labial fusion, absence of vagina, and no gonadal or gonadal duct tissues present at laparotomy. Elevated levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) responded well to intravenous injection of LH-releasing hormone (LH-RH) but did not respond to clomiphene citrate. Both OH and FSH levels were suppressed by administration of testosterone or estrogen. Low serum concentration of testosterone did not respond to human chorionic gonadotropin (hCG) injection. Dihydrotestosterone binding by cultured skin fibroblast revealed the existence of a binding component with low capacity and high affinity. This is the first report of a patient with XY gonadal agenesis in whom androgen receptors in the target cells are demonstrated."}
{"id": "PMID:229450", "title": "Activities of organ characteristic enzymes and noradrenaline and glycogen contents in the Albert hepatoma of C57BL mice.", "content": "Further biochemical characterization of the Albert hepatoma has been performed. The following results were obtained: In spite of often repeated transplantations and a medium growth rate, the Albert hepatoma does still contain organ-characteristic enzymes. We have found significant activities of glucokinase, glucose-6-phosphatase and arginase, and considerable amounts of noradrenaline and glycogen. In addition, it is capable to respond to humoral stimuli, that is, it differs from most of the other hepatocellular malignomas also in this regard.", "contents": "Activities of organ characteristic enzymes and noradrenaline and glycogen contents in the Albert hepatoma of C57BL mice. Further biochemical characterization of the Albert hepatoma has been performed. The following results were obtained: In spite of often repeated transplantations and a medium growth rate, the Albert hepatoma does still contain organ-characteristic enzymes. We have found significant activities of glucokinase, glucose-6-phosphatase and arginase, and considerable amounts of noradrenaline and glycogen. In addition, it is capable to respond to humoral stimuli, that is, it differs from most of the other hepatocellular malignomas also in this regard."}
{"id": "PMID:229454", "title": "Primary empty sella turcica in children. Report of two familial cases.", "content": "The authors describe cranio-facial deformities found in two sisters and associated with spinal anomalies, short stature and delayed skeletal maturation. The principal radiological features were an enlarged J-shaped sella turcica and intrasellar cisternal herniation. Enlargement of optic foramina and internal acoustic canals were also present. These asymptomatic cases of \"empty sella\" seem to be part of a general dysplastic syndrome rather than a local disease.", "contents": "Primary empty sella turcica in children. Report of two familial cases. The authors describe cranio-facial deformities found in two sisters and associated with spinal anomalies, short stature and delayed skeletal maturation. The principal radiological features were an enlarged J-shaped sella turcica and intrasellar cisternal herniation. Enlargement of optic foramina and internal acoustic canals were also present. These asymptomatic cases of \"empty sella\" seem to be part of a general dysplastic syndrome rather than a local disease."}
{"id": "PMID:229455", "title": "A case of hypertrophic protein losing gastropathy.", "content": "A 3 1/2 year old boy presented with a history of vomiting and generalized oedema. Biochemically proven protein losing enteropathy was associated with huge gastric fundal rugae on barium examination. Gastroscopy confirmed the barium findings but biopsy material demonstrated normal mucosa. The condition regressed on a high protein diet. Cytomegalovirus (CMV) was found in the urine after the illness had subsided.", "contents": "A case of hypertrophic protein losing gastropathy. A 3 1/2 year old boy presented with a history of vomiting and generalized oedema. Biochemically proven protein losing enteropathy was associated with huge gastric fundal rugae on barium examination. Gastroscopy confirmed the barium findings but biopsy material demonstrated normal mucosa. The condition regressed on a high protein diet. Cytomegalovirus (CMV) was found in the urine after the illness had subsided."}
{"id": "PMID:229459", "title": "Mixed and obstructive sleep apnea and near miss for sudden infant death syndrome: 2. Comparison of near miss and normal control infants by age.", "content": "Twenty-nine full-term near miss for sudden infant death syndrome (SIDS) and 30 normal control infants underwent 24-hour polygraphic monitoring. Several types of respiratory events during sleep (eg, central, mixed, and obstructive apnea, periodic breathing) were defined and tabulated. Analysis of these respiratory variables and comparison of groups of near miss and control infants indicated that between 3 weeks and 4 1/2 months of age only one variable was consistently different at a statistically significant level: the number of mixed and obstructive apnea greater than 3 seconds during total sleep time. This study also showed an increase in mixed and obstructive respiratory events during sleep at 6 weeks of age in control as well as in near miss infants.", "contents": "Mixed and obstructive sleep apnea and near miss for sudden infant death syndrome: 2. Comparison of near miss and normal control infants by age. Twenty-nine full-term near miss for sudden infant death syndrome (SIDS) and 30 normal control infants underwent 24-hour polygraphic monitoring. Several types of respiratory events during sleep (eg, central, mixed, and obstructive apnea, periodic breathing) were defined and tabulated. Analysis of these respiratory variables and comparison of groups of near miss and control infants indicated that between 3 weeks and 4 1/2 months of age only one variable was consistently different at a statistically significant level: the number of mixed and obstructive apnea greater than 3 seconds during total sleep time. This study also showed an increase in mixed and obstructive respiratory events during sleep at 6 weeks of age in control as well as in near miss infants."}
{"id": "PMID:229461", "title": "\"It's time, you must wake up now\".", "content": "Seven subjects who claimed to be able to awake accurately from sleep at a predetermined time were required to awake in the sleep laboratory at 03:30 and 05:30 on two separate nights. Eight of the 12 spontaneous awakenings were within +/- 20 min. from the target time, and 8 awakenings were from REM sleep. The two best performing subjects were tested for additional 7 nights in the laboratory but accuracy deteriorated considerably with only 2 awakenings within +/- 20 min. from target time. Approximately 50% of all awakenings, however, were from REM sleep. It is concluded that some individuals are able to awake at predetermined times and that this ability might be dependent on motivational level and the sleep stage.", "contents": "\"It's time, you must wake up now\". Seven subjects who claimed to be able to awake accurately from sleep at a predetermined time were required to awake in the sleep laboratory at 03:30 and 05:30 on two separate nights. Eight of the 12 spontaneous awakenings were within +/- 20 min. from the target time, and 8 awakenings were from REM sleep. The two best performing subjects were tested for additional 7 nights in the laboratory but accuracy deteriorated considerably with only 2 awakenings within +/- 20 min. from target time. Approximately 50% of all awakenings, however, were from REM sleep. It is concluded that some individuals are able to awake at predetermined times and that this ability might be dependent on motivational level and the sleep stage."}
{"id": "PMID:229462", "title": "Distortions of vision and pain: two functional facets of D-lysergic acid diethylamide.", "content": "D-lysergic acid diethylamide (LSD) produces distortions of visual perception and analgesia. Evidence is advanced from a functional standpoint that the observed visual effects result from an attenuation of light-evoked input to the dorsal lateral geniculate nucleus (LGN) from the purely centripetal pathways of the retina. More slowly responding visual afferents or those with more complex receptive fields seem to be affected most. LSD analgesia, accompanied by severe psychotic symptoms, appears to result from drug actions on a centrifugally controlled pain system involving neurons of the midbrain raphe.", "contents": "Distortions of vision and pain: two functional facets of D-lysergic acid diethylamide. D-lysergic acid diethylamide (LSD) produces distortions of visual perception and analgesia. Evidence is advanced from a functional standpoint that the observed visual effects result from an attenuation of light-evoked input to the dorsal lateral geniculate nucleus (LGN) from the purely centripetal pathways of the retina. More slowly responding visual afferents or those with more complex receptive fields seem to be affected most. LSD analgesia, accompanied by severe psychotic symptoms, appears to result from drug actions on a centrifugally controlled pain system involving neurons of the midbrain raphe."}
{"id": "PMID:229465", "title": "Determination of the length distribution of poly(A) at the 3' terminus of the virion RNAs of EMC virus, poliovirus, rhinovirus, RAV-61 and CPMV and of mouse globin mRNA.", "content": "Rapid, detailed, and accurate analysis of the length spectrum of 3' terminal poly(A) in an RNA population can be obtained by 3'-terminal 32P-labelling of RNA with T4 RNA ligase, digestion with ribonucleases T1 and A, and use of gel sequencing methods. Length distributions of 3'-terminal poly(A) of EMC virus, poliovirus, rhinovirus, RAV-61, and CPMV virion RNAs as well as mouse globin mRNA are presented.", "contents": "Determination of the length distribution of poly(A) at the 3' terminus of the virion RNAs of EMC virus, poliovirus, rhinovirus, RAV-61 and CPMV and of mouse globin mRNA. Rapid, detailed, and accurate analysis of the length spectrum of 3' terminal poly(A) in an RNA population can be obtained by 3'-terminal 32P-labelling of RNA with T4 RNA ligase, digestion with ribonucleases T1 and A, and use of gel sequencing methods. Length distributions of 3'-terminal poly(A) of EMC virus, poliovirus, rhinovirus, RAV-61, and CPMV virion RNAs as well as mouse globin mRNA are presented."}
{"id": "PMID:229466", "title": "A convenient sequencing method for 5' protein-linked RNAs.", "content": "A convenient nucleotide sequencing method for 5' end protein-linked RNAs was developed. Genome of LSc, 2ab poliovirus, which has a protein (VPg) covalently linked to the 5' terminus, was labelled with 125I Bolton and Hunter reagent after proteinase K treatment. No sign of labelling of nucleotide moiety in the genome with the reagent was detected. A labelled oligo peptide-linked ribonuclease T1 fragment was obtained from the 5' end of the genome. Analysis of the complex by two dimensional gel electrophoresis after partial alkali digestion or by the nucleotide sequencing method of Donis-Keller et al. (1) revealed that LSc, 2ab strain genome had an identical 5' end structure to that of Mahoney strain genome, that is, VPg-pUpUpApApApApCpApGp. Our results have shown that this labelling method is useful for analysis of 5' end sequence of RNAs linked to protein at the 5' termini.", "contents": "A convenient sequencing method for 5' protein-linked RNAs. A convenient nucleotide sequencing method for 5' end protein-linked RNAs was developed. Genome of LSc, 2ab poliovirus, which has a protein (VPg) covalently linked to the 5' terminus, was labelled with 125I Bolton and Hunter reagent after proteinase K treatment. No sign of labelling of nucleotide moiety in the genome with the reagent was detected. A labelled oligo peptide-linked ribonuclease T1 fragment was obtained from the 5' end of the genome. Analysis of the complex by two dimensional gel electrophoresis after partial alkali digestion or by the nucleotide sequencing method of Donis-Keller et al. (1) revealed that LSc, 2ab strain genome had an identical 5' end structure to that of Mahoney strain genome, that is, VPg-pUpUpApApApApCpApGp. Our results have shown that this labelling method is useful for analysis of 5' end sequence of RNAs linked to protein at the 5' termini."}
{"id": "PMID:229475", "title": "Malignant fibrous histiocytoma of bone and osteosarcoma. A comparative light and electron microscopic study.", "content": "Malignant fibrous histiocytomas are well-described tumors of the soft tissues. Recent investigations have shown that malignant histiocytoma may also occur as a primary bone tumor. However, difficulties may arise to distinguish malignant histiocytoma of bone from other malignant bone tumors, such as osteosarcoma. In the present study, the ultrastructure of five cases of malignant fibrous histiocytoma of bone is compared with that of osteosarcoma. The results show that malignant fibrous histiocytoma is composed mainly of histiocytic cells and fibroblastic cells. In addition, xanthomatous cells, undifferentiated cells, and giant cells may be observed. By contrast, the predominant cell type in osteosarcoma is the neoplastic osteoblast, characterized by abundant rough endoplasmic reticulum. Signs of matrix calcification in the intercellular matrix between the collagen fibrils are regularly observed in osteosarcoma, but not in malignant histiocytoma. From these results it is concluded that the ultrastructure of malignant fibrous histiocytoma arising in bone is morphologically identical with the soft tissue counterpart of this tumor. The components of the tumor are derived from neoplastic histiocytes. This cytogenesis differs from that of osteosarcoma, which is derived from neoplastic osteoblasts. Therefore, from the ultrastructural point of view, malignant fibrous histiocytoma of bone should be accepted as a distinct histologic entity among bone tumors.", "contents": "Malignant fibrous histiocytoma of bone and osteosarcoma. A comparative light and electron microscopic study. Malignant fibrous histiocytomas are well-described tumors of the soft tissues. Recent investigations have shown that malignant histiocytoma may also occur as a primary bone tumor. However, difficulties may arise to distinguish malignant histiocytoma of bone from other malignant bone tumors, such as osteosarcoma. In the present study, the ultrastructure of five cases of malignant fibrous histiocytoma of bone is compared with that of osteosarcoma. The results show that malignant fibrous histiocytoma is composed mainly of histiocytic cells and fibroblastic cells. In addition, xanthomatous cells, undifferentiated cells, and giant cells may be observed. By contrast, the predominant cell type in osteosarcoma is the neoplastic osteoblast, characterized by abundant rough endoplasmic reticulum. Signs of matrix calcification in the intercellular matrix between the collagen fibrils are regularly observed in osteosarcoma, but not in malignant histiocytoma. From these results it is concluded that the ultrastructure of malignant fibrous histiocytoma arising in bone is morphologically identical with the soft tissue counterpart of this tumor. The components of the tumor are derived from neoplastic histiocytes. This cytogenesis differs from that of osteosarcoma, which is derived from neoplastic osteoblasts. Therefore, from the ultrastructural point of view, malignant fibrous histiocytoma of bone should be accepted as a distinct histologic entity among bone tumors."}
{"id": "PMID:229476", "title": "Ectopic ACTH syndrome from bronchogenic carcinoma in association with chronic lymphocytic leukaemia.", "content": "A patient under treatment for chronic lymphocytic leukaemia developed lobar pneumonia after 8 months. When antileukaemic therapy was discontinued, features of an ectopic ACTH syndrome developed, secondary to bronchogenic carcinoma. Exogenous steroid therapy for leukaemia seemed to suppress the clinical manifestations of the ectopic ACTH syndrome while subsequent endogenous steroid production controlled the peripheral lymphocyte count.", "contents": "Ectopic ACTH syndrome from bronchogenic carcinoma in association with chronic lymphocytic leukaemia. A patient under treatment for chronic lymphocytic leukaemia developed lobar pneumonia after 8 months. When antileukaemic therapy was discontinued, features of an ectopic ACTH syndrome developed, secondary to bronchogenic carcinoma. Exogenous steroid therapy for leukaemia seemed to suppress the clinical manifestations of the ectopic ACTH syndrome while subsequent endogenous steroid production controlled the peripheral lymphocyte count."}
{"id": "PMID:229477", "title": "Genetic nature of regression of Rous sarcoma virus-induced tumors in crosses of Regional Poultry Research Laboratory lines 6 and 7(2).", "content": "Regional Poultry Research Laboratory (RPRL) inbred lines 6(1), 6(3), and 7(2) and F1, F2, and reciprocal backcross progenies of these lines were used to investigate host-gene effects upon the regression of Rous sarcoma virus (RSV)-induced tumors. Lines 6(1) and 6(3) were susceptible to subgroup A and C lymphoid leukosis (LL) viruses and line 7(2) was resistant to subgroup A but was segregating for susceptibility to subgroup C LL virus. Viruses of RSV subgroups A and C were used. Lines 6(1), 6(3), and 7(2) were homozygous for shared blood group alleles B2, C5, L1 and r. The incidence of tumor regression was higher in line 6(3) than in 7(2), and in reciprocal F1 crosses of these lines was of the same order of magnitude as in line 6(3). Progeny from F1 generation parents mated to line 6(3) had a higher frequency of regression than offspring from F1 generation parents mated to line 7(2). The frequency of regression in F2 generation offspring was intermediate between the two backcrosses. The data suggest that either a locus (or loci) other than L and B has a role in Rous tumor regression in this species or the immune response region of the B blood group-major histocompatibility complex differs in the two lines even though the serological and/or graft vs. host regions have not been shown to differ.", "contents": "Genetic nature of regression of Rous sarcoma virus-induced tumors in crosses of Regional Poultry Research Laboratory lines 6 and 7(2). Regional Poultry Research Laboratory (RPRL) inbred lines 6(1), 6(3), and 7(2) and F1, F2, and reciprocal backcross progenies of these lines were used to investigate host-gene effects upon the regression of Rous sarcoma virus (RSV)-induced tumors. Lines 6(1) and 6(3) were susceptible to subgroup A and C lymphoid leukosis (LL) viruses and line 7(2) was resistant to subgroup A but was segregating for susceptibility to subgroup C LL virus. Viruses of RSV subgroups A and C were used. Lines 6(1), 6(3), and 7(2) were homozygous for shared blood group alleles B2, C5, L1 and r. The incidence of tumor regression was higher in line 6(3) than in 7(2), and in reciprocal F1 crosses of these lines was of the same order of magnitude as in line 6(3). Progeny from F1 generation parents mated to line 6(3) had a higher frequency of regression than offspring from F1 generation parents mated to line 7(2). The frequency of regression in F2 generation offspring was intermediate between the two backcrosses. The data suggest that either a locus (or loci) other than L and B has a role in Rous tumor regression in this species or the immune response region of the B blood group-major histocompatibility complex differs in the two lines even though the serological and/or graft vs. host regions have not been shown to differ."}
{"id": "PMID:229478", "title": "Development of gluconeogenic, glycolytic, and pentose-shunt enzymes in the chicken kidney.", "content": "The activities of the key gluconeogenic, glycolytic, and pentose-shunt enzymes in chicken kidney were determined starting from 8 days before to 58 days after hatching. The activities of pyruvate carboxylase (PC), mitochondrial and cytosolic phosphoenolypruvate carboxykinase (PEPCK), fructose-1,6-diphosphatase (FDPase) and glucose-6-phosphatase (G6Pase) were low in the embryonic tissue but increased towards the time of hatching. After hatching, the activities of PC, mitochondrial PEPCK, and G6Pase continued to increase, but those of FDPase and cytosolic PEPCK decreased. Relatively little change in these activities was observed in chickens over 24 days old. The activities of hexokinase (HK), phosphofructokinase (PFK), pyruvate kinase (PK), and lactate dehydrogenase (LDH) increased during embryonic growth. After hatching, HK activity continued to increase and then decrease, whereas PFK appeared to decrease and then increase to prehatch levels in 28-day-old birds. LDH activity continued to increase until 8 days after hatching and remained constant thereafter. No definite pattern was discernible in the case of PK. As for the pentose-shunt enzymes, there was no significant change in glucose-6-phosphate dehydrogenase activity (G6PDH), but the activity of 6-phosphogluconate dehydrogenase (6PGDH) increased until the chickens were 14 days old and then remained relatively constant.", "contents": "Development of gluconeogenic, glycolytic, and pentose-shunt enzymes in the chicken kidney. The activities of the key gluconeogenic, glycolytic, and pentose-shunt enzymes in chicken kidney were determined starting from 8 days before to 58 days after hatching. The activities of pyruvate carboxylase (PC), mitochondrial and cytosolic phosphoenolypruvate carboxykinase (PEPCK), fructose-1,6-diphosphatase (FDPase) and glucose-6-phosphatase (G6Pase) were low in the embryonic tissue but increased towards the time of hatching. After hatching, the activities of PC, mitochondrial PEPCK, and G6Pase continued to increase, but those of FDPase and cytosolic PEPCK decreased. Relatively little change in these activities was observed in chickens over 24 days old. The activities of hexokinase (HK), phosphofructokinase (PFK), pyruvate kinase (PK), and lactate dehydrogenase (LDH) increased during embryonic growth. After hatching, HK activity continued to increase and then decrease, whereas PFK appeared to decrease and then increase to prehatch levels in 28-day-old birds. LDH activity continued to increase until 8 days after hatching and remained constant thereafter. No definite pattern was discernible in the case of PK. As for the pentose-shunt enzymes, there was no significant change in glucose-6-phosphate dehydrogenase activity (G6PDH), but the activity of 6-phosphogluconate dehydrogenase (6PGDH) increased until the chickens were 14 days old and then remained relatively constant."}
{"id": "PMID:229479", "title": "[Change in the phosphatase activity in rice seeds of varying germination].", "content": "Activities of ATPase, acid and alkaline pyrophosphatases and phytase in the germs and endosperms of rice seeds of varying germinative power were measured during their swelling and germination. Maximum ATPase activity was found in the cytoplasmic fraction. Activity of pyrophosphatase was higher in the germ and that of phytase in the endosperm. As the swelling and germination continued, the enzyme activity increased. Losses of germinating power during prolonged storage were accompanied by a decline in the activity of the enzymes which, however, never disappeared; the activity of pyrophosphatases was maintained by 55-70% and that of ATPase and phytase by 40-44%.", "contents": "[Change in the phosphatase activity in rice seeds of varying germination]. Activities of ATPase, acid and alkaline pyrophosphatases and phytase in the germs and endosperms of rice seeds of varying germinative power were measured during their swelling and germination. Maximum ATPase activity was found in the cytoplasmic fraction. Activity of pyrophosphatase was higher in the germ and that of phytase in the endosperm. As the swelling and germination continued, the enzyme activity increased. Losses of germinating power during prolonged storage were accompanied by a decline in the activity of the enzymes which, however, never disappeared; the activity of pyrophosphatases was maintained by 55-70% and that of ATPase and phytase by 40-44%."}
{"id": "PMID:229480", "title": "[Rapid biological method for assessing D-vitamin supply of chicks].", "content": "A segment of the small intestine of chicks turned inside out and pulled on a glass rod was placed into a buffer solution. The Ca2+ consumption from the solution was monitored, using the color murexide reaction. The Ca2+ binding during the first 5 min was much higher in the chicks well supplied with D-vitamin than in the D-vitamin deficient chicks. The level of binding was determined by the content of specific calcium-binding protein in the intestinal mucosa. A close correlation between the dosage of D3-vitamin and the amount of Ca2+ consumed by the intestine from the solution and bound with the mucosa was established. These findings together with the simplicity of the procedure suggest that measurement of the calcium binding capacity of an intestinal segment can be used as a rapid method of assaying the D-vitamin status of the animal.", "contents": "[Rapid biological method for assessing D-vitamin supply of chicks]. A segment of the small intestine of chicks turned inside out and pulled on a glass rod was placed into a buffer solution. The Ca2+ consumption from the solution was monitored, using the color murexide reaction. The Ca2+ binding during the first 5 min was much higher in the chicks well supplied with D-vitamin than in the D-vitamin deficient chicks. The level of binding was determined by the content of specific calcium-binding protein in the intestinal mucosa. A close correlation between the dosage of D3-vitamin and the amount of Ca2+ consumed by the intestine from the solution and bound with the mucosa was established. These findings together with the simplicity of the procedure suggest that measurement of the calcium binding capacity of an intestinal segment can be used as a rapid method of assaying the D-vitamin status of the animal."}
{"id": "PMID:229481", "title": "[Synthesis of D-ribulose-1,5-diphosphate with immobilized enzymes of Thiobacillus].", "content": "Preparative synthesis of D-ribulose-1,5-diphosphate (RuDP) from ribose-5-phosphate and ATP was carried out, using as a catalyst a crude extract of Thiobacillus thiooxidans 58 R immobilized on porous glass. The methods for immobiliztion of crude bacterial extracts, synthesis of RuDP and purification of the resultant product by means of column chromatography on activated charcoal and anionites were developed. The structure of RuDP was identified by 13C-NMR spectroscopy. Stability of two phosphate groups of RuDP during acid and alkaline hydrolysis proved to be different: both phosphate groups were completely removed in 1 N H2SO4 at 100 degrees C whereas only one phosphate group was hydrolysed in 1 N NaOH at 25 degrees C. This finding is at variance with the earlier results of Horecker et al. (1956).", "contents": "[Synthesis of D-ribulose-1,5-diphosphate with immobilized enzymes of Thiobacillus]. Preparative synthesis of D-ribulose-1,5-diphosphate (RuDP) from ribose-5-phosphate and ATP was carried out, using as a catalyst a crude extract of Thiobacillus thiooxidans 58 R immobilized on porous glass. The methods for immobiliztion of crude bacterial extracts, synthesis of RuDP and purification of the resultant product by means of column chromatography on activated charcoal and anionites were developed. The structure of RuDP was identified by 13C-NMR spectroscopy. Stability of two phosphate groups of RuDP during acid and alkaline hydrolysis proved to be different: both phosphate groups were completely removed in 1 N H2SO4 at 100 degrees C whereas only one phosphate group was hydrolysed in 1 N NaOH at 25 degrees C. This finding is at variance with the earlier results of Horecker et al. (1956)."}
{"id": "PMID:229499", "title": "Effects of acetazolamide and changes of acid-base balance on the content of cyclic nucleotides in the rat kidney.", "content": "Changes in tissue levels of cyclic adenosine 3':5'-monophosphate (cAMP) and cyclic guanosine 3':5'-monophosphate (cGMP) in the rat kidney in response to acid-base changes and administration of acetazolamide were measured. cAMP was determined according to the method described by Gilman and cGMP by radioimmunoassay. 1 mg/kg acetazolamide increased bicarbonate excretion 100-fold over the control values to 2.52 +/- 0.5 mEq/min (mean +/- SEM; n = 6), but did not influence cGMP and cAMP tissue content. 10 and 100 mg/kg acetazolamide increased cGMP tissue levels to 0.277 +/- 0.048 and 0.482 +/- 0.07 pmol/mg dry weight in comparison to 0.192 +/- 0.04 in the controls, whereas no changes in cAMP levels occurred. Chronic as well as acute metabolic alkalosis induced an increase of cGMP levels (0.26 +/- 0.03 and 0.29 +/- 0.06 pmol/mg), whereas chronic metabolic and acute respiratory acidosis lowered cGMP levels to 0.14 +/- 0.02 and 0.13 +/- 0.02 pmol/mg. cAMP tissue levels were not affected by changes in acid-base balance. The data could suggest that cGMP participates in the regulation of acid-base balance and renal effects of acetazolamide.", "contents": "Effects of acetazolamide and changes of acid-base balance on the content of cyclic nucleotides in the rat kidney. Changes in tissue levels of cyclic adenosine 3':5'-monophosphate (cAMP) and cyclic guanosine 3':5'-monophosphate (cGMP) in the rat kidney in response to acid-base changes and administration of acetazolamide were measured. cAMP was determined according to the method described by Gilman and cGMP by radioimmunoassay. 1 mg/kg acetazolamide increased bicarbonate excretion 100-fold over the control values to 2.52 +/- 0.5 mEq/min (mean +/- SEM; n = 6), but did not influence cGMP and cAMP tissue content. 10 and 100 mg/kg acetazolamide increased cGMP tissue levels to 0.277 +/- 0.048 and 0.482 +/- 0.07 pmol/mg dry weight in comparison to 0.192 +/- 0.04 in the controls, whereas no changes in cAMP levels occurred. Chronic as well as acute metabolic alkalosis induced an increase of cGMP levels (0.26 +/- 0.03 and 0.29 +/- 0.06 pmol/mg), whereas chronic metabolic and acute respiratory acidosis lowered cGMP levels to 0.14 +/- 0.02 and 0.13 +/- 0.02 pmol/mg. cAMP tissue levels were not affected by changes in acid-base balance. The data could suggest that cGMP participates in the regulation of acid-base balance and renal effects of acetazolamide."}
{"id": "PMID:229498", "title": "Reactivity of isolated bovine facial vessels to electric stimulation and to drugs.", "content": "The effects of electric stimulation on isometric force generation of isolated helical strips of bovine facial arteries (BFA) and veins (BFV) were investigated. Whereas BFA always contracted, electrically stimulated BFV showed a biphasic response, i.e. a small, transient contraction followed by an intense relaxation. The findings presented suggest a neurogenic response for the vasodilator component of BFV response to electric stimulation. Exogenous catecholamines and serotonin dilated the veins; the effects were antagonized by propranolol and dihydroergotamine, respectively. Dopamine-induced relaxations were only partially inhibited by propranolol; the residual relaxations were antagonized by chlorpormazine and haloperidol. Relaxations of the veins after electric stimulation or after administration of noradrenaline were accompanied by an increase of the cAMP content. In the BFA catecholamines, serotonin and histamine increased the tension, whereas isoprenaline was ineffective. Acetylcholine contracted the veins and relaxed the arteries; both effects were antagonized by atropine.", "contents": "Reactivity of isolated bovine facial vessels to electric stimulation and to drugs. The effects of electric stimulation on isometric force generation of isolated helical strips of bovine facial arteries (BFA) and veins (BFV) were investigated. Whereas BFA always contracted, electrically stimulated BFV showed a biphasic response, i.e. a small, transient contraction followed by an intense relaxation. The findings presented suggest a neurogenic response for the vasodilator component of BFV response to electric stimulation. Exogenous catecholamines and serotonin dilated the veins; the effects were antagonized by propranolol and dihydroergotamine, respectively. Dopamine-induced relaxations were only partially inhibited by propranolol; the residual relaxations were antagonized by chlorpormazine and haloperidol. Relaxations of the veins after electric stimulation or after administration of noradrenaline were accompanied by an increase of the cAMP content. In the BFA catecholamines, serotonin and histamine increased the tension, whereas isoprenaline was ineffective. Acetylcholine contracted the veins and relaxed the arteries; both effects were antagonized by atropine."}
{"id": "PMID:229500", "title": "Analgesia induced by cold-water stress: attenuation following hypophysectomy.", "content": "In addition to the well-known activation of the pituitary-adrenal axis, acute exposure to severe stressors includes a temporary analgesia in rats. Thus, the present study investigates whether the pituitary was involved in the mediation of analgesia induced by severe cold-water swim (CWS) stress. Flinch-jump thresholds were measured 30 min following 3.5-min swims in water temperatures ranging from 2-35 degrees C. Compared with untreated normal rats, hypophysectomized rats, receiving corticosterone and thyroxin, displayed significantly less CWS-induced analgesia, while similarly-supplemented normal rats exhibited significantly more CWS-induced analgesia. In a second experiment, operant liminal escape pain thresholds were determined following acute and chronic CWS. Whereas normal rats exhibited profound analgesia following the initial swims, the hypophysectomized rats never displayed any CWS-induced operant escape shifts. Stress-induced alterations in general activity levels and/or thermoregulation were shown to be unrelated to the diminished effectiveness of CNS to produce analgesia in hypophysectomized rats. These data imply that the pituitary is involved in the mediation of CWS-induced analgesia.", "contents": "Analgesia induced by cold-water stress: attenuation following hypophysectomy. In addition to the well-known activation of the pituitary-adrenal axis, acute exposure to severe stressors includes a temporary analgesia in rats. Thus, the present study investigates whether the pituitary was involved in the mediation of analgesia induced by severe cold-water swim (CWS) stress. Flinch-jump thresholds were measured 30 min following 3.5-min swims in water temperatures ranging from 2-35 degrees C. Compared with untreated normal rats, hypophysectomized rats, receiving corticosterone and thyroxin, displayed significantly less CWS-induced analgesia, while similarly-supplemented normal rats exhibited significantly more CWS-induced analgesia. In a second experiment, operant liminal escape pain thresholds were determined following acute and chronic CWS. Whereas normal rats exhibited profound analgesia following the initial swims, the hypophysectomized rats never displayed any CWS-induced operant escape shifts. Stress-induced alterations in general activity levels and/or thermoregulation were shown to be unrelated to the diminished effectiveness of CNS to produce analgesia in hypophysectomized rats. These data imply that the pituitary is involved in the mediation of CWS-induced analgesia."}
{"id": "PMID:229501", "title": "Some effects of an ACTH 4-9 analog (Org 2766) on human performance.", "content": "The effects (on human beings) of the ACTH analog Org 2766 were investigated for a range of performance tests: complicated serial reaction task, running memory span, verbal learning and non-verbal mental ability tests (closure flexibility and non-verbal abstraction). Subjective ratings on feelings were taken and heart rate was measured. Only the 30-min reaction task produced significant drug effects. In this task performance tends to deteriorate as a function of time on task. During the test period there is a gradual increase in the number of lapses in performance due to moments of inattention. This deterioration is counteracted by the ACTH 4-9 analog, a result also found in previous study using ACTH 4-10 (Org OI63). Thus ACTH fragments which are devoid of endocrine effects seem to have a beneficial effect on goal-directed motivation oriented on the requirements of the task.", "contents": "Some effects of an ACTH 4-9 analog (Org 2766) on human performance. The effects (on human beings) of the ACTH analog Org 2766 were investigated for a range of performance tests: complicated serial reaction task, running memory span, verbal learning and non-verbal mental ability tests (closure flexibility and non-verbal abstraction). Subjective ratings on feelings were taken and heart rate was measured. Only the 30-min reaction task produced significant drug effects. In this task performance tends to deteriorate as a function of time on task. During the test period there is a gradual increase in the number of lapses in performance due to moments of inattention. This deterioration is counteracted by the ACTH 4-9 analog, a result also found in previous study using ACTH 4-10 (Org OI63). Thus ACTH fragments which are devoid of endocrine effects seem to have a beneficial effect on goal-directed motivation oriented on the requirements of the task."}
{"id": "PMID:229502", "title": "Neuromuscular transmission in some hindlimb muscles of piglets with congenital myofibrillar hypoplasia (splayleg).", "content": "Seventeen new-born piglets of hybrid stock were tested for defects of neuromuscular transmission by stimulation electromyography (EMG). Nine of these displayed extreme symptoms of muscle weakness (splayleg), while the others were their clinically normal littermates. Muscles from four different functional groups were investigated, including the gastrocnemius, tibialis anterior, knee flexors and thigh adductors. Repetitive stimulation of muscle nerves at 3 Hz gave comparable peak-to-peak amplitudes of the EMG response in splayleg and control piglets (mean values from 5 to 10 mV). The lowest mean EMG response values at this stimulation frequency were found in splayleg adductor muscles of the thigh which were not, however significantly different from the controls. Higher frequencies of stimulation (30, 50 and 100 Hz), in general, led to a less pronounced decrease of EMG amplitude in splayleg piglet muscles than in the controls, with the exception of knee flexors. Neither splayleg nor control muscles exhibited post-activation exhaustion or post-tetanic potentiation. It is being concluded from these results that congenital myofibrillar hypoplasia is not primarily a myasthenia-like syndrome, but that either excitation-contraction coupling or the contractile mechanism itself are primarily affected.", "contents": "Neuromuscular transmission in some hindlimb muscles of piglets with congenital myofibrillar hypoplasia (splayleg). Seventeen new-born piglets of hybrid stock were tested for defects of neuromuscular transmission by stimulation electromyography (EMG). Nine of these displayed extreme symptoms of muscle weakness (splayleg), while the others were their clinically normal littermates. Muscles from four different functional groups were investigated, including the gastrocnemius, tibialis anterior, knee flexors and thigh adductors. Repetitive stimulation of muscle nerves at 3 Hz gave comparable peak-to-peak amplitudes of the EMG response in splayleg and control piglets (mean values from 5 to 10 mV). The lowest mean EMG response values at this stimulation frequency were found in splayleg adductor muscles of the thigh which were not, however significantly different from the controls. Higher frequencies of stimulation (30, 50 and 100 Hz), in general, led to a less pronounced decrease of EMG amplitude in splayleg piglet muscles than in the controls, with the exception of knee flexors. Neither splayleg nor control muscles exhibited post-activation exhaustion or post-tetanic potentiation. It is being concluded from these results that congenital myofibrillar hypoplasia is not primarily a myasthenia-like syndrome, but that either excitation-contraction coupling or the contractile mechanism itself are primarily affected."}
{"id": "PMID:229503", "title": "Depressed affect as a cause of associated somatic problems.", "content": "Depressed affect as a cause of associated somatic problems is explored by means of data on affect, appetite, energy, and sleep collected from a community sample and from subsamples contacted after each of several time lags. The analysis of the data indicates that depressed affect is a cause of the major somatic problems associated with it. It is suspected that depressed affect involves continuing high density neural firing which, over a period of months, causes a reduction of post-synaptic biogenic amine receptor cell sensitivity in the brainstem, with the diencephalon as the major site. This results in a functional impairment responsible for the somatic problems.", "contents": "Depressed affect as a cause of associated somatic problems. Depressed affect as a cause of associated somatic problems is explored by means of data on affect, appetite, energy, and sleep collected from a community sample and from subsamples contacted after each of several time lags. The analysis of the data indicates that depressed affect is a cause of the major somatic problems associated with it. It is suspected that depressed affect involves continuing high density neural firing which, over a period of months, causes a reduction of post-synaptic biogenic amine receptor cell sensitivity in the brainstem, with the diencephalon as the major site. This results in a functional impairment responsible for the somatic problems."}
{"id": "PMID:229505", "title": "Characterization of 3H-GABA receptor binding to rat brain synaptosomal membranes: effect of non GABAergic compounds.", "content": "Characteristics of 3H-GABA binding to rat brain synaptic membranes in vitro have been investigated. The specific binding of 3H-GABA displays saturation kinetics. Only one single population of receptor sites was found (Km = 31.3 nM) with a concentration of 2.09 pmol/mg protein. Only GABA agonists show inhibitory effect on the binding, whereas GABA antagonists, GABA-uptake inhibitors, and inhibitors of GAD and GABA-T are without effect. The order of potencies for GABA agonists are: Muscimol greater than GABA greater than or equal to 4,5-dihydromuscimol greater than 3-aminoproprane sulphonic acid greater than isoguvacine greater than THIP greater than 3-hydroxy-GABA greater than imidazol-4-acetic acid. Agonists and antagonists from other neurone systems as well as neuroleptics and benzodiazepines had no or only a very slight potency in the binding test.", "contents": "Characterization of 3H-GABA receptor binding to rat brain synaptosomal membranes: effect of non GABAergic compounds. Characteristics of 3H-GABA binding to rat brain synaptic membranes in vitro have been investigated. The specific binding of 3H-GABA displays saturation kinetics. Only one single population of receptor sites was found (Km = 31.3 nM) with a concentration of 2.09 pmol/mg protein. Only GABA agonists show inhibitory effect on the binding, whereas GABA antagonists, GABA-uptake inhibitors, and inhibitors of GAD and GABA-T are without effect. The order of potencies for GABA agonists are: Muscimol greater than GABA greater than or equal to 4,5-dihydromuscimol greater than 3-aminoproprane sulphonic acid greater than isoguvacine greater than THIP greater than 3-hydroxy-GABA greater than imidazol-4-acetic acid. Agonists and antagonists from other neurone systems as well as neuroleptics and benzodiazepines had no or only a very slight potency in the binding test."}
{"id": "PMID:229506", "title": "Personality dependent effects of the ACTH 4--10 fragment on test performances and on concomitant autonomic reactions.", "content": "The effect of the ACTH-fragment 4--10 (30 mg SC) on a mental performance test and on some concomitant cardiovascular changes was investigated in comparison with a placebo in a double blind cross-over study. The subjects were either mainly extraverted or mainly introverted according to Eysenck's 'Maudsley Personality Inventory'. Under the influence of the heptapeptide extraverted subjects achieved a higher total score in the mental task performance with a smaller increase of forearm blood flow and of heart rate than under the influence of the placebo. In contrast, under the influence of the placebo introverted subjects achieved a higher total score in the mental task performance with a smaller increase of forearm blood flow and of heart rate than under the influence of the ACTH-fragment. Personality, therefore, determines to some degree how this centrally acting heptapeptide influences efficiency in the mental task performance and the concomitant cardiovascular changes.", "contents": "Personality dependent effects of the ACTH 4--10 fragment on test performances and on concomitant autonomic reactions. The effect of the ACTH-fragment 4--10 (30 mg SC) on a mental performance test and on some concomitant cardiovascular changes was investigated in comparison with a placebo in a double blind cross-over study. The subjects were either mainly extraverted or mainly introverted according to Eysenck's 'Maudsley Personality Inventory'. Under the influence of the heptapeptide extraverted subjects achieved a higher total score in the mental task performance with a smaller increase of forearm blood flow and of heart rate than under the influence of the placebo. In contrast, under the influence of the placebo introverted subjects achieved a higher total score in the mental task performance with a smaller increase of forearm blood flow and of heart rate than under the influence of the ACTH-fragment. Personality, therefore, determines to some degree how this centrally acting heptapeptide influences efficiency in the mental task performance and the concomitant cardiovascular changes."}
{"id": "PMID:229511", "title": "[Bronchial arteriography and intraarterial chemotherapy in bronchogenic carcinoma (author's transl)].", "content": "Selective bronchial angiography and short term intra-arterial infusions of Mitomycin C were performed in 70 patients with bronchogenic carcinoma. The courses were given 1--5 times with a median interval of 2 weeks. The angiograms were compared with chest radiograms and data obtained at bronchoscopy, mediastinoscopy, surgery or autopsy. The effect of therapy was evaluated with chest radiography and bronchoscopy. Among our first 36 patients an objective response was registered in 18/27 patients with squamous cell carcinoma, in 4/7 with adenocarcinoma and in 2/2 with small cell cancer. These results warrant further studies. Though not suitable as a routine procedure in the diagnostic work up of a patient with possible bronchogenic carcinoma bronchial angiogrpahy may contribute to a better staging when used e.g. in connection with intraarterial chemotherapy.", "contents": "[Bronchial arteriography and intraarterial chemotherapy in bronchogenic carcinoma (author's transl)]. Selective bronchial angiography and short term intra-arterial infusions of Mitomycin C were performed in 70 patients with bronchogenic carcinoma. The courses were given 1--5 times with a median interval of 2 weeks. The angiograms were compared with chest radiograms and data obtained at bronchoscopy, mediastinoscopy, surgery or autopsy. The effect of therapy was evaluated with chest radiography and bronchoscopy. Among our first 36 patients an objective response was registered in 18/27 patients with squamous cell carcinoma, in 4/7 with adenocarcinoma and in 2/2 with small cell cancer. These results warrant further studies. Though not suitable as a routine procedure in the diagnostic work up of a patient with possible bronchogenic carcinoma bronchial angiogrpahy may contribute to a better staging when used e.g. in connection with intraarterial chemotherapy."}
{"id": "PMID:229520", "title": "Mammalian endogenous peroxidases as cellular markers and as biosynthetic endpoints of hormone-mediated activity: viewpoint from cytochemistry.", "content": "Aldehyde-resistant, diaminobenzidine-stained endogenous peroxidases form ideal markers for the biochemical endpoints of hormone stimulation and differentiation of certain mammalian cells and tissues. The lactoperoxidase (LPO)-type of endogenous peroxidases are synthesized by the acinar cells of the salivary, Harderian, lacrimal and mammary glands and are present in their secretions. These LPO-type enzymes, that are inhibited by cyanide and aminotriazole, appear to operate extracellularly as bactericidal agents in milk and in other biological fluids. In the mammary gland, lactoperoxidase is a consistent marker enzyme for differentiated acinar cells engaged in lactogenesis. Myeloperoxidase (MPO)-type endogenous peroxidases are prominent markers for the GERL endomembrane system and differentiated lysosomes in certain cells of the reticuloendothelial system and phagocytes. MPO is prominent within eosinophils, peritoneal macrophages and in Kupffer cells. The MPO-type endogenous peroxidases function primarily within lysosomes as bactericidal agents. Thyroid peroxidase (TPO) is relegated to the cisternae of the granular endoplasmic reticulum and Golgi apparatus, to apical cytoplasmic vesicles and to the luminar cell membrane surface of acinar cells. The enzyme is probably activated at release and functions both in the organification reaction (T leads to To) and in the biosynthesis of thyroxine. Thyroid stimulating hormone (TSH) appears to play a key role in the regulation of TPO levels and activity in the thyroid gland. Certain tissues displaying growth-dependency on estrogen (i.e., uterus, cervix, vagina and the DMBA-induced rat mammary tumor) synthesize and secrete endogenous peroxidase into their lumina. These enzymes serve as important marker proteins of estrogen action, in that they occur distal to the binding of estrogen to its receptor protein. Estrogen antagonists, particularly CI-628 (Parke-Davis) and Nafoxidine (Upjohn) that appear to function through the estrogen receptor mechanism, also induce synthesis of the reproductive tract endogenous peroxidase but inhibit growth of these tissues. Progesterone antagonizes the synthesis of the reproductive tract peroxidases and inhibits growth of the tissues as well, in part, through the reduction of the cytosol estrogen receptor protein. Endogenous peroxidase activity appears to represent a reliable marker for rodent breast cancer tissues displaying dependency for estrogen and is of potential interest as a diagnostic marker protein in human breast cancer. Rat uterine peroxidase (UP) has been investigated by microelectrophoretic techniques. The molecular weight of UP has been determined in the range of 100,000 by using polyacrylamide gradient gels in the absence and presence of nonionic and anionic detergents. The isoelectric point of UP is located between pH 4.5 and 5.9. Employing the two-dimensional combination of isoelectric focusing and gel gradient electrophoresis, UP was separated into two subunits, one having a molecular weight of 70,000, the other less than 20,000.", "contents": "Mammalian endogenous peroxidases as cellular markers and as biosynthetic endpoints of hormone-mediated activity: viewpoint from cytochemistry. Aldehyde-resistant, diaminobenzidine-stained endogenous peroxidases form ideal markers for the biochemical endpoints of hormone stimulation and differentiation of certain mammalian cells and tissues. The lactoperoxidase (LPO)-type of endogenous peroxidases are synthesized by the acinar cells of the salivary, Harderian, lacrimal and mammary glands and are present in their secretions. These LPO-type enzymes, that are inhibited by cyanide and aminotriazole, appear to operate extracellularly as bactericidal agents in milk and in other biological fluids. In the mammary gland, lactoperoxidase is a consistent marker enzyme for differentiated acinar cells engaged in lactogenesis. Myeloperoxidase (MPO)-type endogenous peroxidases are prominent markers for the GERL endomembrane system and differentiated lysosomes in certain cells of the reticuloendothelial system and phagocytes. MPO is prominent within eosinophils, peritoneal macrophages and in Kupffer cells. The MPO-type endogenous peroxidases function primarily within lysosomes as bactericidal agents. Thyroid peroxidase (TPO) is relegated to the cisternae of the granular endoplasmic reticulum and Golgi apparatus, to apical cytoplasmic vesicles and to the luminar cell membrane surface of acinar cells. The enzyme is probably activated at release and functions both in the organification reaction (T leads to To) and in the biosynthesis of thyroxine. Thyroid stimulating hormone (TSH) appears to play a key role in the regulation of TPO levels and activity in the thyroid gland. Certain tissues displaying growth-dependency on estrogen (i.e., uterus, cervix, vagina and the DMBA-induced rat mammary tumor) synthesize and secrete endogenous peroxidase into their lumina. These enzymes serve as important marker proteins of estrogen action, in that they occur distal to the binding of estrogen to its receptor protein. Estrogen antagonists, particularly CI-628 (Parke-Davis) and Nafoxidine (Upjohn) that appear to function through the estrogen receptor mechanism, also induce synthesis of the reproductive tract endogenous peroxidase but inhibit growth of these tissues. Progesterone antagonizes the synthesis of the reproductive tract peroxidases and inhibits growth of the tissues as well, in part, through the reduction of the cytosol estrogen receptor protein. Endogenous peroxidase activity appears to represent a reliable marker for rodent breast cancer tissues displaying dependency for estrogen and is of potential interest as a diagnostic marker protein in human breast cancer. Rat uterine peroxidase (UP) has been investigated by microelectrophoretic techniques. The molecular weight of UP has been determined in the range of 100,000 by using polyacrylamide gradient gels in the absence and presence of nonionic and anionic detergents. The isoelectric point of UP is located between pH 4.5 and 5.9. Employing the two-dimensional combination of isoelectric focusing and gel gradient electrophoresis, UP was separated into two subunits, one having a molecular weight of 70,000, the other less than 20,000."}
{"id": "PMID:229531", "title": "Effect of alcohol on the plasma cAMP response to glucagon.", "content": "Prior studies indicated that acute ethanol feeding induced a decrease in adrenergic sensitivity as measured by the plasma cAMP response to isoproterenol. In this report we show that two hours after acute ethanol ingestion the plasma cyclic AMP levels were increased 8.5 fold 6 minutes after glucagon injection. Saline controls showed a 35 fold increase in plasma cAMP levels after glucagon injection. It is suggested that the decreased response caused by ethanol may be due to a decrease in the sensitivity of glucagon receptors.", "contents": "Effect of alcohol on the plasma cAMP response to glucagon. Prior studies indicated that acute ethanol feeding induced a decrease in adrenergic sensitivity as measured by the plasma cAMP response to isoproterenol. In this report we show that two hours after acute ethanol ingestion the plasma cyclic AMP levels were increased 8.5 fold 6 minutes after glucagon injection. Saline controls showed a 35 fold increase in plasma cAMP levels after glucagon injection. It is suggested that the decreased response caused by ethanol may be due to a decrease in the sensitivity of glucagon receptors."}
{"id": "PMID:229532", "title": "Comparison of duration of immunity in chickens infected with a live infectious bronchitis vaccine by three different routes.", "content": "Three groups of chicks were vaccinated by aerosol, intra-ocular and drinking water routes with a live infectious bronchitis (IB) vaccine. At one, two, six, 15 and 32 weeks after vaccination five birds from each group were sampled for testing for IB haemagglutination-inhibiting (HI) antibodies and challenged. Assessment of susceptibility to infection was measured by recovery of virus from individual tracheas and from kidney and gonad pools four days after challenge. Virus was isolated from all kidney and gonad pools of birds challenged one week after vaccination, the kidney and gonad pools of the drinking water vaccinates at two weeks, the kidney pool of the intra-ocular group at 15 weeks and all organ pools except the gonads of the intra-ocular group at 32 weeks. Tracheal resistance was found in most of the birds challenged one week after vaccination and in all the birds tested at two weeks but had begun to wane by six weeks after vaccination. No correlation was found between low HI antibody titres of individual birds and their susceptibility to challenge measured by reisolation of virus from the traches, but birds with titres over log2 6 were always resistant.", "contents": "Comparison of duration of immunity in chickens infected with a live infectious bronchitis vaccine by three different routes. Three groups of chicks were vaccinated by aerosol, intra-ocular and drinking water routes with a live infectious bronchitis (IB) vaccine. At one, two, six, 15 and 32 weeks after vaccination five birds from each group were sampled for testing for IB haemagglutination-inhibiting (HI) antibodies and challenged. Assessment of susceptibility to infection was measured by recovery of virus from individual tracheas and from kidney and gonad pools four days after challenge. Virus was isolated from all kidney and gonad pools of birds challenged one week after vaccination, the kidney and gonad pools of the drinking water vaccinates at two weeks, the kidney pool of the intra-ocular group at 15 weeks and all organ pools except the gonads of the intra-ocular group at 32 weeks. Tracheal resistance was found in most of the birds challenged one week after vaccination and in all the birds tested at two weeks but had begun to wane by six weeks after vaccination. No correlation was found between low HI antibody titres of individual birds and their susceptibility to challenge measured by reisolation of virus from the traches, but birds with titres over log2 6 were always resistant."}
{"id": "PMID:229533", "title": "Airway response to adrenergic agonists and antagonists in 3-day- to 2-year-old rats.", "content": "The response of the airways to adrenergic agonists and antagonists was studied in 3-day- to 2-year-old and bronchitic rats. The results showed that the alpha-adrenoceptors are not functional at birth but become so by 8 weeks. In contrast, the beta-adrenoceptor effects are demonstrable on the third day after birth. The mean decrease in airway luminal diameter after beta-adrenergic blockade was greater in bronchitic than in healthy animals and was interpreted to be due to the increased sensitivity of the beta-adrenoceptors in bronchitis.", "contents": "Airway response to adrenergic agonists and antagonists in 3-day- to 2-year-old rats. The response of the airways to adrenergic agonists and antagonists was studied in 3-day- to 2-year-old and bronchitic rats. The results showed that the alpha-adrenoceptors are not functional at birth but become so by 8 weeks. In contrast, the beta-adrenoceptor effects are demonstrable on the third day after birth. The mean decrease in airway luminal diameter after beta-adrenergic blockade was greater in bronchitic than in healthy animals and was interpreted to be due to the increased sensitivity of the beta-adrenoceptors in bronchitis."}
{"id": "PMID:229541", "title": "[Studies of the proteins in normal bronchial secretion].", "content": "Parallel determinations were made, of 10 individual serum proteins and of proteins in the bronchial secretion obtained by aspiration from 8 subjects that did not show manifest bronchopulmonary disease. By application of the formula suggested by Deuschl and Johansson it was found that 37 percent of IgG, 84,5 percent of IgA, 48,9 percent of transferrins, 15,2 percent of alpha-1-anti-trypsin and 11,3 percent of ceruloplasmin present in the bronchial secretion are synthetised in the bronchial mucosa itself, while the rest occur as a result of diffusion from the blood. Acid alpha-1-glycoprotein and haptoglobin from the bronchial secretion originate in the blood. IgM was evidenced in the bronchial aspirate in only 3 subjects, and alpha-2 macroglobulin was not found in any of the subjects.", "contents": "[Studies of the proteins in normal bronchial secretion]. Parallel determinations were made, of 10 individual serum proteins and of proteins in the bronchial secretion obtained by aspiration from 8 subjects that did not show manifest bronchopulmonary disease. By application of the formula suggested by Deuschl and Johansson it was found that 37 percent of IgG, 84,5 percent of IgA, 48,9 percent of transferrins, 15,2 percent of alpha-1-anti-trypsin and 11,3 percent of ceruloplasmin present in the bronchial secretion are synthetised in the bronchial mucosa itself, while the rest occur as a result of diffusion from the blood. Acid alpha-1-glycoprotein and haptoglobin from the bronchial secretion originate in the blood. IgM was evidenced in the bronchial aspirate in only 3 subjects, and alpha-2 macroglobulin was not found in any of the subjects."}
{"id": "PMID:229543", "title": "[Adverse reactions to antitubercular treatment with rifampin (Considerations on 14 cases].", "content": "An analysis of a group of 120 patients with pulmonary tuberculosis undergoing rifampicin treatment attempted to perform a study of adverse reactions induced by this drug used in modern therapeutic regimens of short duration (6 to 9 months). This was prompted by the increasing number of papers in the specialized literature concerned with such adverse reactions that occur in 10--50 percent of all cases treated with rifampicin. Adverse reactions to rifampicin (influenza-like syndrome, digestive syndrome, hepatic syndrome) were relatively rare in the group presented here (11,8 percent), when compared with the data in the literature. Although no severe adverse reactions occured, suppression of rifampicin therapy was necessary in most of the cases, and this modified the efficiency of the treatment. This low incidence has however a statistical significance indicating that larger groups should be investigated.", "contents": "[Adverse reactions to antitubercular treatment with rifampin (Considerations on 14 cases]. An analysis of a group of 120 patients with pulmonary tuberculosis undergoing rifampicin treatment attempted to perform a study of adverse reactions induced by this drug used in modern therapeutic regimens of short duration (6 to 9 months). This was prompted by the increasing number of papers in the specialized literature concerned with such adverse reactions that occur in 10--50 percent of all cases treated with rifampicin. Adverse reactions to rifampicin (influenza-like syndrome, digestive syndrome, hepatic syndrome) were relatively rare in the group presented here (11,8 percent), when compared with the data in the literature. Although no severe adverse reactions occured, suppression of rifampicin therapy was necessary in most of the cases, and this modified the efficiency of the treatment. This low incidence has however a statistical significance indicating that larger groups should be investigated."}
{"id": "PMID:229546", "title": "[Virological diagnosis of enteroviral diseases].", "content": "68 human enteroviruses are responsible for many acute viral diseases. An economic diagnostic procedure is discussed and documented by the author's own findings. Virus isolation is regarded as the method of choice, for epidemiological reasons and in view of the fact that enteroviruses are often isolated within a few days.", "contents": "[Virological diagnosis of enteroviral diseases]. 68 human enteroviruses are responsible for many acute viral diseases. An economic diagnostic procedure is discussed and documented by the author's own findings. Virus isolation is regarded as the method of choice, for epidemiological reasons and in view of the fact that enteroviruses are often isolated within a few days."}
{"id": "PMID:229544", "title": "[Recurrent bronchopulmonary infections due to humoral immune deficiency].", "content": "Between 1974 and 1978 11 patients were detected, in a pneumology department. They were classified as follows: stage I, with relatively benign bronchial infections; 5 patients were included in this group, all of them made uneventful recoveries, without sequellae; stage II was characterised by more severe infections, that required repeated hospitalisation. Five more patients were included in this group. The patients in these two stages had either selective IgA deficiencies or combined (IgA and IgM) deficiencies. In stage III the disease had a severe evolution, characterised by extensive pulmonary tissue destruction and permanent suppuration. One patient had agammaglobulinemia in which the deficiency of serum and secretory bronchial immunoglobulins was complete. Although immunoglobulins represent only a part of the defense mechanisms of the respiratory pathways, their dosage is however recommended in all cases in which anamnesis, symptomatology or the evolution of the disease suggest the possibility of selective or total immunoglobulin deficiencies.", "contents": "[Recurrent bronchopulmonary infections due to humoral immune deficiency]. Between 1974 and 1978 11 patients were detected, in a pneumology department. They were classified as follows: stage I, with relatively benign bronchial infections; 5 patients were included in this group, all of them made uneventful recoveries, without sequellae; stage II was characterised by more severe infections, that required repeated hospitalisation. Five more patients were included in this group. The patients in these two stages had either selective IgA deficiencies or combined (IgA and IgM) deficiencies. In stage III the disease had a severe evolution, characterised by extensive pulmonary tissue destruction and permanent suppuration. One patient had agammaglobulinemia in which the deficiency of serum and secretory bronchial immunoglobulins was complete. Although immunoglobulins represent only a part of the defense mechanisms of the respiratory pathways, their dosage is however recommended in all cases in which anamnesis, symptomatology or the evolution of the disease suggest the possibility of selective or total immunoglobulin deficiencies."}
{"id": "PMID:229547", "title": "[The effect of lipid level lowering diets on bile lipids and plasma lipoproteins in normal persons].", "content": "The effects of two fat-modified diets, one rich in polyunsaturated and the other in oleic acids, were studied in 10 healthy young males with regard to bile lipid composition, plasma lipids and lipoproteins. The two experimental diets were given for 2 weeks each and findings compared with those from the subject's normal diet. The fat-modified diets had marked but comparable effects on plasma total cholesterol (decreases by 23% and 16% respectively), on LDL-cholesterol (decreases by 27% and 17% respectively) and on HDL-cholesterol (decreases by 26% and 27% respectively). HDL apolipoproteins A-I and A-II were unaffected. Therefore, the apo A-I/HDL-cholesterol and apo A-II/HDL-cholesterol ratios significantly increased. The \"lithogenic index\" as a measure for the relationship of cholesterol to bile acids and phospholipids, and thus for the solubility of cholesterol in gallbladder bile, was not affected by the lipid lowering diets, which therefore should not increase the risk of cholelithiasis.", "contents": "[The effect of lipid level lowering diets on bile lipids and plasma lipoproteins in normal persons]. The effects of two fat-modified diets, one rich in polyunsaturated and the other in oleic acids, were studied in 10 healthy young males with regard to bile lipid composition, plasma lipids and lipoproteins. The two experimental diets were given for 2 weeks each and findings compared with those from the subject's normal diet. The fat-modified diets had marked but comparable effects on plasma total cholesterol (decreases by 23% and 16% respectively), on LDL-cholesterol (decreases by 27% and 17% respectively) and on HDL-cholesterol (decreases by 26% and 27% respectively). HDL apolipoproteins A-I and A-II were unaffected. Therefore, the apo A-I/HDL-cholesterol and apo A-II/HDL-cholesterol ratios significantly increased. The \"lithogenic index\" as a measure for the relationship of cholesterol to bile acids and phospholipids, and thus for the solubility of cholesterol in gallbladder bile, was not affected by the lipid lowering diets, which therefore should not increase the risk of cholelithiasis."}
{"id": "PMID:229548", "title": "Clinical and etiological heterogeneity of idiopathic diabetes mellitus. The banting memorial lecture.", "content": "We have presented and reviewed evidence for the heterogeneous nature of diabetes mellitus in terms of genetics, environmental factors, insulin responses to glucose and vascular disease. We have reviewed evidence for heterogeneity between juvenile-onset diabetes (JOD) and maturity-onset diabetes (MOD) and maturity-onset diabetes of young (MODY) and for heterogeneity within groups of JOD and MOD and MODY patients. Although much remains to be learned, a beginning has been made and suggests that primary diabetes mellitus is not a single specific disease but a syndrome comprised of a variety of diseases all characterized by hyperglycemia and tissue changes that result from heterogeneous etiologic and pathogenetic factors. Future classifications of primary diabetes mellitus will undoubtedly be lengthy, as are for other diseases and syndromes also caused by a variety of etiologic and pathogenetic mechanisms.", "contents": "Clinical and etiological heterogeneity of idiopathic diabetes mellitus. The banting memorial lecture. We have presented and reviewed evidence for the heterogeneous nature of diabetes mellitus in terms of genetics, environmental factors, insulin responses to glucose and vascular disease. We have reviewed evidence for heterogeneity between juvenile-onset diabetes (JOD) and maturity-onset diabetes (MOD) and maturity-onset diabetes of young (MODY) and for heterogeneity within groups of JOD and MOD and MODY patients. Although much remains to be learned, a beginning has been made and suggests that primary diabetes mellitus is not a single specific disease but a syndrome comprised of a variety of diseases all characterized by hyperglycemia and tissue changes that result from heterogeneous etiologic and pathogenetic factors. Future classifications of primary diabetes mellitus will undoubtedly be lengthy, as are for other diseases and syndromes also caused by a variety of etiologic and pathogenetic mechanisms."}
{"id": "PMID:229549", "title": "[Retrospective study of 149 cases of hepatitis B virus infections. Study of markers and of evolution].", "content": "A retrospective study has been performed in 149 subjects with present or past HBs antigenemia. The group consisted of 8 asymptomatic carriers, 90 with acute hepatitis, 7 with fulminating hepatitis, 27 with chronic hepatitis, 16 with cirrhosis and 1 with hepatoma. The changes from one clinical condition to another, the sources of infection, the percentage of acute hepatitis in the history of chronic hepatitis cases and the working capacity an average of two years after the infection were studied. HBe antigen and the corresponding antibody were detected by immunodiffusion and the results compared with the clinical course.", "contents": "[Retrospective study of 149 cases of hepatitis B virus infections. Study of markers and of evolution]. A retrospective study has been performed in 149 subjects with present or past HBs antigenemia. The group consisted of 8 asymptomatic carriers, 90 with acute hepatitis, 7 with fulminating hepatitis, 27 with chronic hepatitis, 16 with cirrhosis and 1 with hepatoma. The changes from one clinical condition to another, the sources of infection, the percentage of acute hepatitis in the history of chronic hepatitis cases and the working capacity an average of two years after the infection were studied. HBe antigen and the corresponding antibody were detected by immunodiffusion and the results compared with the clinical course."}
{"id": "PMID:229550", "title": "[Clinical aspect of herpes zoster and the pathogenesis of symptomatic cranial nerve zosters].", "content": "The prognosis of shingles is generally good, however if cranial nerves are affected, the course of disease may be very serious. It is still doubtful if latent virus-in the sense of a trigger mechanism-may be activated by dental surgical interventions and cause a symptomatic herpes zoster of cranial nerves. Serious loss of teeth as an oral manifestation of shingles, with panostitis and retarded healing show the seriousness of the tissue changes. The virus can invade the plexus between the facial and trigeminal nerves and can thus travel within the same epineural sheath from one nerve to the other. It follows that in each case of a herpes zoster of cranial nerves, irrespective of location, no dental surgery should be undertaken, even in the initial stage, because - it may increase the extension of the disease along the nerves - it may cause a viraemia - it may initiate uncalled for intraoperative and postoperative complications. Therapy with high doses of antibiotics is indicated.", "contents": "[Clinical aspect of herpes zoster and the pathogenesis of symptomatic cranial nerve zosters]. The prognosis of shingles is generally good, however if cranial nerves are affected, the course of disease may be very serious. It is still doubtful if latent virus-in the sense of a trigger mechanism-may be activated by dental surgical interventions and cause a symptomatic herpes zoster of cranial nerves. Serious loss of teeth as an oral manifestation of shingles, with panostitis and retarded healing show the seriousness of the tissue changes. The virus can invade the plexus between the facial and trigeminal nerves and can thus travel within the same epineural sheath from one nerve to the other. It follows that in each case of a herpes zoster of cranial nerves, irrespective of location, no dental surgery should be undertaken, even in the initial stage, because - it may increase the extension of the disease along the nerves - it may cause a viraemia - it may initiate uncalled for intraoperative and postoperative complications. Therapy with high doses of antibiotics is indicated."}
{"id": "PMID:229551", "title": "[Cervical syndrome].", "content": "The cervical syndrome is described and the possibility of facial pain. Pathologic changes in the anatomical buildup of the cervical spine with its nerve and vascular systems may cause symptoms which may not be recognized for their relationship to the cervical spine. There are no anatomical nervous connections between the maxillofacial and the cervical region, and yet there is evidence of maxillofacial pain caused by cervical factors. The dentist must often answer questions of this nature. The therapy of cervical disease is difficult and requires knowledge, experience and intuition from the treating physician.", "contents": "[Cervical syndrome]. The cervical syndrome is described and the possibility of facial pain. Pathologic changes in the anatomical buildup of the cervical spine with its nerve and vascular systems may cause symptoms which may not be recognized for their relationship to the cervical spine. There are no anatomical nervous connections between the maxillofacial and the cervical region, and yet there is evidence of maxillofacial pain caused by cervical factors. The dentist must often answer questions of this nature. The therapy of cervical disease is difficult and requires knowledge, experience and intuition from the treating physician."}
{"id": "PMID:229552", "title": "Killing of fibroblasts by dexamethasone or dibutyryl adenosine 3',5'-monophosphate is not a valid test for cystic fibrosis.", "content": "Assays based on the counting of total cells and of colony-forming cells were used to demonstrate that neither dexamethasone nor dibutyryl adenosine 3',5'-monophosphate (cyclic AMP) kills human fibroblasts under a variety of conditions. These results contradict those of previous studies showing that dexamethasone and dibutyryl cyclic AMP kill a higher percentage of fibroblasts from normal humans than from individuals with cystic fibrosis.", "contents": "Killing of fibroblasts by dexamethasone or dibutyryl adenosine 3',5'-monophosphate is not a valid test for cystic fibrosis. Assays based on the counting of total cells and of colony-forming cells were used to demonstrate that neither dexamethasone nor dibutyryl adenosine 3',5'-monophosphate (cyclic AMP) kills human fibroblasts under a variety of conditions. These results contradict those of previous studies showing that dexamethasone and dibutyryl cyclic AMP kill a higher percentage of fibroblasts from normal humans than from individuals with cystic fibrosis."}
{"id": "PMID:229553", "title": "[Study of blood glucose regulation in 103 cases of adult acquired hypothyro\u00efdism (author's transl)].", "content": "Systematic studies of blood glucose regulation have been performed in 103 cases of adult acquired hypothyro\u00efdism. The results were the following: 11 cases of overt diabetes were discovered. The diagnostic was made when fasting blood glucose was superior to 120 mg/100 ml and glucosuria was present. 22 cases of asymptomatic (chemical) diabetes. The diagnosis was based on the abnormalities of the oral glucose tolerance test (OGTT). The criteria were those of Fajans and Conn. In 70 cases the results were normal. The comparison of these results with these obtained in a matched population of normal subjects did not show significative differences. Particularly the proportion of \"flat curves\" during the OGTT were not higher in cases of hypothyro\u00efdism. Plasma insulin levels were determined in 20 cases of hypothyro\u00efdism during OGTT. The results were the same as in non-hypothyro\u00efd subjects. The abnormalities of glucose regulation observed in hypothyro\u00efdism were not related to sex, age, overweight or cause of the disease. The number of diabetic patients is not significatively more important in cases of hypothyro\u00efdism of immunological origin (especially Hashimoto's disease.", "contents": "[Study of blood glucose regulation in 103 cases of adult acquired hypothyro\u00efdism (author's transl)]. Systematic studies of blood glucose regulation have been performed in 103 cases of adult acquired hypothyro\u00efdism. The results were the following: 11 cases of overt diabetes were discovered. The diagnostic was made when fasting blood glucose was superior to 120 mg/100 ml and glucosuria was present. 22 cases of asymptomatic (chemical) diabetes. The diagnosis was based on the abnormalities of the oral glucose tolerance test (OGTT). The criteria were those of Fajans and Conn. In 70 cases the results were normal. The comparison of these results with these obtained in a matched population of normal subjects did not show significative differences. Particularly the proportion of \"flat curves\" during the OGTT were not higher in cases of hypothyro\u00efdism. Plasma insulin levels were determined in 20 cases of hypothyro\u00efdism during OGTT. The results were the same as in non-hypothyro\u00efd subjects. The abnormalities of glucose regulation observed in hypothyro\u00efdism were not related to sex, age, overweight or cause of the disease. The number of diabetic patients is not significatively more important in cases of hypothyro\u00efdism of immunological origin (especially Hashimoto's disease."}
{"id": "PMID:229555", "title": "[Association of scleroderma with primary biliary cirrhosis (author's transl)].", "content": "A new case of Reynold's syndrome is reported. This patient was a 70 years old woman with scleroderma (grade II) and PBC (grade III - IV), associated with Sj\u00f6gren's syndrome and cryoglobulinemia. She experienced 10 years earlier Raynaud's syndrome and arthralgia. A review of the Literature reveals 22 other detailed cases whose data are collected in this study. Considerations upon a common pathophysiology for scleroderma, PBC and Sj\u00f6gren's syndrome are developed. Impairment of the function of suppressor T cells in patients undergoing these diseases is possible.", "contents": "[Association of scleroderma with primary biliary cirrhosis (author's transl)]. A new case of Reynold's syndrome is reported. This patient was a 70 years old woman with scleroderma (grade II) and PBC (grade III - IV), associated with Sj\u00f6gren's syndrome and cryoglobulinemia. She experienced 10 years earlier Raynaud's syndrome and arthralgia. A review of the Literature reveals 22 other detailed cases whose data are collected in this study. Considerations upon a common pathophysiology for scleroderma, PBC and Sj\u00f6gren's syndrome are developed. Impairment of the function of suppressor T cells in patients undergoing these diseases is possible."}
{"id": "PMID:229556", "title": "[The primary neoplasm of the gall-bladder. Report of 55 cases (author's transl)].", "content": "The authors report 55 cases of primary neoplasms of the bladder which represent 5,2 per cent of cholecystectomies, their study prove its very important deadly character. They insist on the necessity of the immediatly systematic examination. This examination permit a knowledge of the in situ stades and permit to make adapted surgical treatment. This treatment may be a cholecystectomy if it's a in situ type adenocarcinoma but it must be an enlarged cholecystectomy in all the other cases.", "contents": "[The primary neoplasm of the gall-bladder. Report of 55 cases (author's transl)]. The authors report 55 cases of primary neoplasms of the bladder which represent 5,2 per cent of cholecystectomies, their study prove its very important deadly character. They insist on the necessity of the immediatly systematic examination. This examination permit a knowledge of the in situ stades and permit to make adapted surgical treatment. This treatment may be a cholecystectomy if it's a in situ type adenocarcinoma but it must be an enlarged cholecystectomy in all the other cases."}
{"id": "PMID:229557", "title": "[Bone and calcium metabolism in adult hypothyroidism (author's transl)].", "content": "A study of blood and urinary calcium and phosphorus, 25 hydroxyvitamin D plasma level (25 OH D3), bone radiology and hystology is performed in 12 hypothyro\u00efd adult patients. This study confirms the notion of myxoedematous ost\u00e9opetrosis. Radiologic and histologic findings shows an osteocondensation, more important on the skull, and augmentation of cortical thickness of the bones is noted. Quantitative histologic findings, shows some signs of diminution of bone cellular activity. Low plasma level of 25 OH D3 in these patients is discussed in the view of an event of a disturb in the metabolism of D-vitamin in hypothyro\u00efdism.", "contents": "[Bone and calcium metabolism in adult hypothyroidism (author's transl)]. A study of blood and urinary calcium and phosphorus, 25 hydroxyvitamin D plasma level (25 OH D3), bone radiology and hystology is performed in 12 hypothyro\u00efd adult patients. This study confirms the notion of myxoedematous ost\u00e9opetrosis. Radiologic and histologic findings shows an osteocondensation, more important on the skull, and augmentation of cortical thickness of the bones is noted. Quantitative histologic findings, shows some signs of diminution of bone cellular activity. Low plasma level of 25 OH D3 in these patients is discussed in the view of an event of a disturb in the metabolism of D-vitamin in hypothyro\u00efdism."}
{"id": "PMID:229558", "title": "[Clinical test in current psychopathologie (author's transl)].", "content": "This clinical test, concerning the use of tiapride, was carried out for one year on 60 patients, with weekly or bi-mensual check-ups in a neuropsychiatric office, with no other associated medication capable of modifying either vigilance or humor. Tiapride, on top of its excellent tolerance (except for patients presenting a hysterical type structure), and apart from being a sedative for anxiety, turned out to be, on one hand, a disinhibitor for states of depression (even more so when accompanying psychosomatic symptomatology was apparent), and on the other hand a semeiological analyser inasmuch as it can help discern the underlying psychopathological structure.", "contents": "[Clinical test in current psychopathologie (author's transl)]. This clinical test, concerning the use of tiapride, was carried out for one year on 60 patients, with weekly or bi-mensual check-ups in a neuropsychiatric office, with no other associated medication capable of modifying either vigilance or humor. Tiapride, on top of its excellent tolerance (except for patients presenting a hysterical type structure), and apart from being a sedative for anxiety, turned out to be, on one hand, a disinhibitor for states of depression (even more so when accompanying psychosomatic symptomatology was apparent), and on the other hand a semeiological analyser inasmuch as it can help discern the underlying psychopathological structure."}
{"id": "PMID:229559", "title": "[Acute intoxications by tricyclic antidepressants (author's transl)].", "content": "The authors report 87 cases of acute voluntary intoxications with tricyclic antidepressants. They essentially studied the cardiac complications; and conclude that the prognosis is more severe than for other intoxications.", "contents": "[Acute intoxications by tricyclic antidepressants (author's transl)]. The authors report 87 cases of acute voluntary intoxications with tricyclic antidepressants. They essentially studied the cardiac complications; and conclude that the prognosis is more severe than for other intoxications."}
{"id": "PMID:229560", "title": "[Hereditary dysfibrinogenaemia. Study of a family (author's transl)].", "content": "This note studies fourteen members of the same family over three generations. Ten of them have biological dysfibrinogenaemia without haemorrhagic diathesis or thrombosis. The diagnostic is essentially based on the study of fibrin formation by thrombine time. On the other hand global coagulation tests are little or not at all disturbed and the rate of physiologically active fibrinogen is sometimes subnormal. The biological outline of the defect is superposable to the one of the majority of hereditary dysfibrinogenaemia cases actually published. The classical prevailing autosomal transmission is confirmed.", "contents": "[Hereditary dysfibrinogenaemia. Study of a family (author's transl)]. This note studies fourteen members of the same family over three generations. Ten of them have biological dysfibrinogenaemia without haemorrhagic diathesis or thrombosis. The diagnostic is essentially based on the study of fibrin formation by thrombine time. On the other hand global coagulation tests are little or not at all disturbed and the rate of physiologically active fibrinogen is sometimes subnormal. The biological outline of the defect is superposable to the one of the majority of hereditary dysfibrinogenaemia cases actually published. The classical prevailing autosomal transmission is confirmed."}
{"id": "PMID:229561", "title": "[Study of some immune functions in cardiac patients undergoing an extra-corporeal circulation operation (author's transl)].", "content": "61 adult patients (36 men, 25 women), with coronary or valvular diseases, operated with extra-corporeal circulation, by the same surgical team, have been investigated for the plasmatic levels of total complement, fractions C4, C3 activator, C3, immunoglobulins G, A and M, for the phagocytic and bactericidal activity of polymorphonuclear leucocytes. 50 healthy adults (26 men, 24 women) have been tested as controls. Results have been statistically analyzed. Two experiments have also been performed: extra-corporeal circulation machine has run alone without a patient, and the examinations of blood samples in the machine have been performed before and at the end of the running time. Just at the end of extra-corporeal circulation, a deep and significant falling of globulins (complement and its fractions, immunoglobulins) is observed, which lasts during two days; at the 8th and 15th days after the operation, a significant and important raising of these globulins is noted. It has been demonstrated that the initial falling is not correlated with the hemodilution, but is relevant to a consumption in the machine and in the tissues. Any significant variation in polymorphonuclear leucocytes activity has not been noted, but there are strong individual variations. Importance of humoral abnormalities observed is discussed, regarding to the infectious prophylaxis in cardiac surgery.", "contents": "[Study of some immune functions in cardiac patients undergoing an extra-corporeal circulation operation (author's transl)]. 61 adult patients (36 men, 25 women), with coronary or valvular diseases, operated with extra-corporeal circulation, by the same surgical team, have been investigated for the plasmatic levels of total complement, fractions C4, C3 activator, C3, immunoglobulins G, A and M, for the phagocytic and bactericidal activity of polymorphonuclear leucocytes. 50 healthy adults (26 men, 24 women) have been tested as controls. Results have been statistically analyzed. Two experiments have also been performed: extra-corporeal circulation machine has run alone without a patient, and the examinations of blood samples in the machine have been performed before and at the end of the running time. Just at the end of extra-corporeal circulation, a deep and significant falling of globulins (complement and its fractions, immunoglobulins) is observed, which lasts during two days; at the 8th and 15th days after the operation, a significant and important raising of these globulins is noted. It has been demonstrated that the initial falling is not correlated with the hemodilution, but is relevant to a consumption in the machine and in the tissues. Any significant variation in polymorphonuclear leucocytes activity has not been noted, but there are strong individual variations. Importance of humoral abnormalities observed is discussed, regarding to the infectious prophylaxis in cardiac surgery."}
{"id": "PMID:229563", "title": "[Therapeutic advances in geriatry. A report on 47 cases (author's transl)].", "content": "A group of 47 elderly patients with various ailments and aged between 66 and 99 years were treated with tiapride: very good results were obtained in 7 cases of severe buccofacial dyskinesia, though the dosage had to go as high as 800 mg/day; results were excellent in 2 cases, good in 9, moderate in 5, and nil in 3 out of 19 patients with agitated states; overall results were good (1 failure) in 8 cases of alcoholism (4 acute and 4 chronic); 8 good results and 4 failures were noted in 12 patients with either cancer pain, or pain following zoster or due to arthrosis or migraine. The product was very well-tolerated by these elderly patients.", "contents": "[Therapeutic advances in geriatry. A report on 47 cases (author's transl)]. A group of 47 elderly patients with various ailments and aged between 66 and 99 years were treated with tiapride: very good results were obtained in 7 cases of severe buccofacial dyskinesia, though the dosage had to go as high as 800 mg/day; results were excellent in 2 cases, good in 9, moderate in 5, and nil in 3 out of 19 patients with agitated states; overall results were good (1 failure) in 8 cases of alcoholism (4 acute and 4 chronic); 8 good results and 4 failures were noted in 12 patients with either cancer pain, or pain following zoster or due to arthrosis or migraine. The product was very well-tolerated by these elderly patients."}
{"id": "PMID:229562", "title": "[Enteral feeding in burn patients].", "content": "The deleterious effects of denutrition, both generally and locally, in the development of extensive burns are widely known. These can be corrected either by reducing the nutritional loss or by increasing the intake. As far as the loss is concerned, the burned area may lead to a veritable \"calorific haemorrhage\", arising in cases where more than 30 to 40% of the body surface is affected. Nitrogen loss occurs in the urine, from the digestive tract, or from the burn itself, and in a 70 kg subject with a 40% burn, it can reach 40 g of nitrogen. This loss can be compensated in four ways: -- though this presents difficulties the oral route; -- the parenteral route; but intravenous feeding is often insufficient or dangerous; -- discontinuous enteral feeding; but this is poorly supported by the patient, badly assimilated, and dangerous; -- low-rate continuous enteral feeding (LRCEF) which is the preferred method. Use is made of continuous flow-rate pumps, which can be regulated and refrigerated (fig. 1). The solutions (fig. 2) are prepared as required and 2 to 3 litres are administered continuously throughout the 24 hour periods. Regular observations are made: -- daily for weight, urine output, blood and urine electrolytes, blood nitrogen and sugar; -- weekly, for protein and lipid electrophoresis. The results obtained during 3 periods (1973, 1975 and 1977) are reviewed.  -- 1973 (19 patients, fig. 3). A cautious attitude prevailed and only one case of a positive cumulative result was noted. The total quantity ingested was never greater than 4 000 calories or 224 g of protein. There were quite a few incidents (fig. 4), and 45 \"accident days\" were reported. -- 1975 (13 patients). The nitrogen balance was occasionally positive. Cumulative results were obtained in 8 cases. There were 26 \"accident days\". Improvement was due to: . prompter recourse to LRCEF, . a more rapid progression in the amount given, . an increase in the maximum quantity, . increased water intake. These results led to the development of the present-day procedure which includes: . a preliminary tolerance-testing period of 8 days, during which intake is increased to 4 000 calories and 25 g of nitrogen, . a second period during which intake is adjusted to losses, with supplementary feeding by the parenteral or oral routes. -- 1977 (36 patients including 18 on water-beds). Better tolerance to the increase in the amounts ingested was recorded in the patients treated on a water-bed. This led to an increase in calories and nitrogen being given to these patients, who also seemed to have a greater ability to make use of the supplementary nitrogen. The use of LRCEF and water-beds, combined, needless to say, with the earliest possible covering of the burned skin area, make a substantial contribution to the reduction of losses in burn patients.", "contents": "[Enteral feeding in burn patients]. The deleterious effects of denutrition, both generally and locally, in the development of extensive burns are widely known. These can be corrected either by reducing the nutritional loss or by increasing the intake. As far as the loss is concerned, the burned area may lead to a veritable \"calorific haemorrhage\", arising in cases where more than 30 to 40% of the body surface is affected. Nitrogen loss occurs in the urine, from the digestive tract, or from the burn itself, and in a 70 kg subject with a 40% burn, it can reach 40 g of nitrogen. This loss can be compensated in four ways: -- though this presents difficulties the oral route; -- the parenteral route; but intravenous feeding is often insufficient or dangerous; -- discontinuous enteral feeding; but this is poorly supported by the patient, badly assimilated, and dangerous; -- low-rate continuous enteral feeding (LRCEF) which is the preferred method. Use is made of continuous flow-rate pumps, which can be regulated and refrigerated (fig. 1). The solutions (fig. 2) are prepared as required and 2 to 3 litres are administered continuously throughout the 24 hour periods. Regular observations are made: -- daily for weight, urine output, blood and urine electrolytes, blood nitrogen and sugar; -- weekly, for protein and lipid electrophoresis. The results obtained during 3 periods (1973, 1975 and 1977) are reviewed.  -- 1973 (19 patients, fig. 3). A cautious attitude prevailed and only one case of a positive cumulative result was noted. The total quantity ingested was never greater than 4 000 calories or 224 g of protein. There were quite a few incidents (fig. 4), and 45 \"accident days\" were reported. -- 1975 (13 patients). The nitrogen balance was occasionally positive. Cumulative results were obtained in 8 cases. There were 26 \"accident days\". Improvement was due to: . prompter recourse to LRCEF, . a more rapid progression in the amount given, . an increase in the maximum quantity, . increased water intake. These results led to the development of the present-day procedure which includes: . a preliminary tolerance-testing period of 8 days, during which intake is increased to 4 000 calories and 25 g of nitrogen, . a second period during which intake is adjusted to losses, with supplementary feeding by the parenteral or oral routes. -- 1977 (36 patients including 18 on water-beds). Better tolerance to the increase in the amounts ingested was recorded in the patients treated on a water-bed. This led to an increase in calories and nitrogen being given to these patients, who also seemed to have a greater ability to make use of the supplementary nitrogen. The use of LRCEF and water-beds, combined, needless to say, with the earliest possible covering of the burned skin area, make a substantial contribution to the reduction of losses in burn patients."}
{"id": "PMID:229564", "title": "[Principles underlying the use of antituberculosis medication in children (author's transl)].", "content": "The authors review the principles underlying antituberculosis therapy in children. Basing their comment on the published literature, they analyze the properties, pharmacology, toxicity, and side-effects of each medication, and define their dosage and modes of administration.", "contents": "[Principles underlying the use of antituberculosis medication in children (author's transl)]. The authors review the principles underlying antituberculosis therapy in children. Basing their comment on the published literature, they analyze the properties, pharmacology, toxicity, and side-effects of each medication, and define their dosage and modes of administration."}
{"id": "PMID:229565", "title": "[Peritonitis by ruptured pyonephrosis (author's transl)].", "content": "The authors have observed one case of peritonitis by ruptured lithiasis pyonephrosis. The elective treatment of this unusual (13th case in the literature) complication of the urinary lithiasis is the nephrectomy.", "contents": "[Peritonitis by ruptured pyonephrosis (author's transl)]. The authors have observed one case of peritonitis by ruptured lithiasis pyonephrosis. The elective treatment of this unusual (13th case in the literature) complication of the urinary lithiasis is the nephrectomy."}
{"id": "PMID:229570", "title": "Traumatic hypopituitarism: anterior hypophyseal insufficiency from indirect cranial trauma.", "content": "We have reported a case of partial hypopituitarism involving deficient ACTH, LH, FSH, and growth hormone production and elevated prolactin. The hypopituitarism was caused by injury to the pituitary resulting from a parachute accident without direct craniocerebral trauma. The pathogenesis of this pituitary injury as either a clivus fracture near the sella, unilated abstruction of the internal carotid artery, and/or direct stalk injury. Clinicians should be alerted to the possibility of hypopituitarism from direct or indirect cranial injuries.", "contents": "Traumatic hypopituitarism: anterior hypophyseal insufficiency from indirect cranial trauma. We have reported a case of partial hypopituitarism involving deficient ACTH, LH, FSH, and growth hormone production and elevated prolactin. The hypopituitarism was caused by injury to the pituitary resulting from a parachute accident without direct craniocerebral trauma. The pathogenesis of this pituitary injury as either a clivus fracture near the sella, unilated abstruction of the internal carotid artery, and/or direct stalk injury. Clinicians should be alerted to the possibility of hypopituitarism from direct or indirect cranial injuries."}
{"id": "PMID:229566", "title": "[Transfusional malaria. Another case (author's transl)].", "content": "Transfusional malaria is an unusual disease. Any fever, happening immediately after blood transfusions must evoke this diagnosis, confirmed by parasites detection in the blood. The treatment is rapidly efficacious. The prophylaxis is at the present time insufficient and would require fluorescent antibody test generalization.", "contents": "[Transfusional malaria. Another case (author's transl)]. Transfusional malaria is an unusual disease. Any fever, happening immediately after blood transfusions must evoke this diagnosis, confirmed by parasites detection in the blood. The treatment is rapidly efficacious. The prophylaxis is at the present time insufficient and would require fluorescent antibody test generalization."}
{"id": "PMID:229567", "title": "[Anatomical and clinical features of a case of gall-bladder abnormality. Results of arteriographic and micro-angiographic studies (author's transl)].", "content": "The authors describe a perplexing clinical picture in which an important factor for diagnosing the lesion in the gall-bladder was hyperselective arteriography of the coeliac trunk, and more especially the hepatic artery. The association of a truc septum in the gall-bladder, without gall-stones, and of another digestive tube lesion, megadolicho-sigmoid and diverticulosis of the sigmoid, would appear to be an extremely rare entity, and this has been the cause of the pain reported by the patient over many years. The cholecystectomy performed appears to be the right choice, and the most effective therapeutic procedure.", "contents": "[Anatomical and clinical features of a case of gall-bladder abnormality. Results of arteriographic and micro-angiographic studies (author's transl)]. The authors describe a perplexing clinical picture in which an important factor for diagnosing the lesion in the gall-bladder was hyperselective arteriography of the coeliac trunk, and more especially the hepatic artery. The association of a truc septum in the gall-bladder, without gall-stones, and of another digestive tube lesion, megadolicho-sigmoid and diverticulosis of the sigmoid, would appear to be an extremely rare entity, and this has been the cause of the pain reported by the patient over many years. The cholecystectomy performed appears to be the right choice, and the most effective therapeutic procedure."}
{"id": "PMID:229574", "title": "Inhibitory effects of non-steroidal anti-inflammatory drugs on human myeloperoxidase.", "content": "Myeloperoxidase with an A420/280 ratio of 0,48 was prepared from normal human leucocytes. This partially purified preparation catalysed guaiacol oxidation, iodination of bovine serum albumin and de-iodination of 125I-thyroxine. Non-steroidal anti-inflammatory drugs (naproxen, indomethacin and flufenamic acid) showed a significant inhibitory effect on myeloperoxidase-catalysed iodination at concentrations of 10(-4)M and higher. Guaiacol also inhibited myeloperoxidase-catalysed iodination, and its iodination inhibition curve was nearly identical to that obtained with the anti-inflammatory drugs. At concentrations between 10(-3)M and 10(-7)M the antiinflammatory drugs had very little or no effect on thyroxine de-iodination. Flufenamic acid and indomethacin, however, inhibited de-iodination significantly at a concentration of 10(-2)M. It is postulated that non-steroidal anti-inflammatory drugs may inhibit myeloperoxidase-catalysed protein iodination by acting as oxidizable cofactors which compete with other oxidizable substrates for oxidants formed by the peroxidase-hydrogen peroxide complex. In view of this and because the myeloperoxidase-hydrogen peroxide system may be involved in inflammatory tissue damage, the possibility should be considered that the action of non-steroidal anti-inflammatory drugs is at least partly attributable to a radical scavenging effect or to sequestration of oxidants.", "contents": "Inhibitory effects of non-steroidal anti-inflammatory drugs on human myeloperoxidase. Myeloperoxidase with an A420/280 ratio of 0,48 was prepared from normal human leucocytes. This partially purified preparation catalysed guaiacol oxidation, iodination of bovine serum albumin and de-iodination of 125I-thyroxine. Non-steroidal anti-inflammatory drugs (naproxen, indomethacin and flufenamic acid) showed a significant inhibitory effect on myeloperoxidase-catalysed iodination at concentrations of 10(-4)M and higher. Guaiacol also inhibited myeloperoxidase-catalysed iodination, and its iodination inhibition curve was nearly identical to that obtained with the anti-inflammatory drugs. At concentrations between 10(-3)M and 10(-7)M the antiinflammatory drugs had very little or no effect on thyroxine de-iodination. Flufenamic acid and indomethacin, however, inhibited de-iodination significantly at a concentration of 10(-2)M. It is postulated that non-steroidal anti-inflammatory drugs may inhibit myeloperoxidase-catalysed protein iodination by acting as oxidizable cofactors which compete with other oxidizable substrates for oxidants formed by the peroxidase-hydrogen peroxide complex. In view of this and because the myeloperoxidase-hydrogen peroxide system may be involved in inflammatory tissue damage, the possibility should be considered that the action of non-steroidal anti-inflammatory drugs is at least partly attributable to a radical scavenging effect or to sequestration of oxidants."}
{"id": "PMID:229575", "title": "Cardiac myofibrillar phosphorylation and adenosine triphosphatase activity.", "content": "When myofibrils from rat hearts were dissolved in concentrated salt solutions and reprecipitated by dilution, they contained both protein kinase (partly cyclic 3':5'-AMP-dependent) and protein phosphatase activities. Troponin-I was the major protein to be phosphorylated by the endogenous myofibril-associated kinase and by added protein kinase. Approximately 1 mole of phosphate per mole of troponin-I was incorporated from radioactive ATP, but the extent of troponin-I phosphorylation could be varied experimentally. An inverse correlation was found between protein phosphorylation and the maximum Ca2+-stimulated myofibrillar Mg2+-ATPase activity, while the amout of calcium required for half-maximum activation was proportional to the extent of protein phosphorylation. The changes in Mg2+-ATPase activity produced in vitro by protein phosphorylation were reproduced in isolated perfused rat hearts treated for short periods with L-noradrenaline (10(-6)M). The changes in myofibrillar function brought about as the result of the phosphorlyation by cAMP-dependent protein kinase suggest that the contractile response is desensitized in order to cope with the rise in intracellular Ca2+ which results from the action of catecholamines on cardiac ventricular cells.", "contents": "Cardiac myofibrillar phosphorylation and adenosine triphosphatase activity. When myofibrils from rat hearts were dissolved in concentrated salt solutions and reprecipitated by dilution, they contained both protein kinase (partly cyclic 3':5'-AMP-dependent) and protein phosphatase activities. Troponin-I was the major protein to be phosphorylated by the endogenous myofibril-associated kinase and by added protein kinase. Approximately 1 mole of phosphate per mole of troponin-I was incorporated from radioactive ATP, but the extent of troponin-I phosphorylation could be varied experimentally. An inverse correlation was found between protein phosphorylation and the maximum Ca2+-stimulated myofibrillar Mg2+-ATPase activity, while the amout of calcium required for half-maximum activation was proportional to the extent of protein phosphorylation. The changes in Mg2+-ATPase activity produced in vitro by protein phosphorylation were reproduced in isolated perfused rat hearts treated for short periods with L-noradrenaline (10(-6)M). The changes in myofibrillar function brought about as the result of the phosphorlyation by cAMP-dependent protein kinase suggest that the contractile response is desensitized in order to cope with the rise in intracellular Ca2+ which results from the action of catecholamines on cardiac ventricular cells."}
{"id": "PMID:229576", "title": "Liver tumours and the contraceptive pill: Controversies in aetiology, diagnosis and management.", "content": "Six female patients seen at Groote Schuur Hospital between 1973 and 1977, with the types of liver lesion that have been linked aetiologically with the contraceptive pill, are described. Four had focal nodular hyperplasia (1 with spontaneous rupture), and 1 patient had a hepatocellular carcinoma. The sixth patient had spontaneous rupture of the liver but no tumour was demonstrated. Based on this experience and a review of the literature, controversies in aetiology, diagnosis and managment are presented. A defined management policy is proposed for the benign lesions, a less aggressive approach being advocated for focal nodular hyperplasia than for hepatic adenoma.", "contents": "Liver tumours and the contraceptive pill: Controversies in aetiology, diagnosis and management. Six female patients seen at Groote Schuur Hospital between 1973 and 1977, with the types of liver lesion that have been linked aetiologically with the contraceptive pill, are described. Four had focal nodular hyperplasia (1 with spontaneous rupture), and 1 patient had a hepatocellular carcinoma. The sixth patient had spontaneous rupture of the liver but no tumour was demonstrated. Based on this experience and a review of the literature, controversies in aetiology, diagnosis and managment are presented. A defined management policy is proposed for the benign lesions, a less aggressive approach being advocated for focal nodular hyperplasia than for hepatic adenoma."}
{"id": "PMID:229577", "title": "Preoperative radiotherapy and chemotherapy in hypervascular, high-grade supratentorial astrocytomas.", "content": "From a group of ten patients with hypervascular, high-grade, supratentorial astrocytomas, five were treated with pre-operative radiotherapy alone, and five with radiotherapy in combination with cytostatic drugs. The aim was to investigate the timing of intracranial operations in the multimodality therapy of brain tumors. The tumor size was diminished only in one case, but tumor vascularization was reduced in half of the cases by the pre-operative treatment. Survival was not improved. Surgical treatment still should be the first of the therapeutic measures. Pre-operative radiotherapy may be of value to reduce tumor vascularization in hypervascular, centrally localized tumors.", "contents": "Preoperative radiotherapy and chemotherapy in hypervascular, high-grade supratentorial astrocytomas. From a group of ten patients with hypervascular, high-grade, supratentorial astrocytomas, five were treated with pre-operative radiotherapy alone, and five with radiotherapy in combination with cytostatic drugs. The aim was to investigate the timing of intracranial operations in the multimodality therapy of brain tumors. The tumor size was diminished only in one case, but tumor vascularization was reduced in half of the cases by the pre-operative treatment. Survival was not improved. Surgical treatment still should be the first of the therapeutic measures. Pre-operative radiotherapy may be of value to reduce tumor vascularization in hypervascular, centrally localized tumors."}
{"id": "PMID:229582", "title": "Mixed malignant tumour of the lung.", "content": "A mixed malignant tumour of the lung intermediate in type between pulmonary blastoma and carcinosarcoma is described. The epithelial component consisted of squamous carcinoma, undifferentiated carcinoma, and clefts lined by bland epithelial cells. The supporting stroma was composed of pleomorphic sarcoma, fibrosarcoma, chondrosarcoma, osteosarcoma, and indeterminate mesenchymal tissue. The tumour was removed surgically, but the patient died postoperatively with rapidly developing multiple bony and soft tissue metastases. Subcutaneous metastases showed the appearnce of poorly differentiated pleomorphic sarcoma. Published reports of mixed malignant lung tumours are reviewed.", "contents": "Mixed malignant tumour of the lung. A mixed malignant tumour of the lung intermediate in type between pulmonary blastoma and carcinosarcoma is described. The epithelial component consisted of squamous carcinoma, undifferentiated carcinoma, and clefts lined by bland epithelial cells. The supporting stroma was composed of pleomorphic sarcoma, fibrosarcoma, chondrosarcoma, osteosarcoma, and indeterminate mesenchymal tissue. The tumour was removed surgically, but the patient died postoperatively with rapidly developing multiple bony and soft tissue metastases. Subcutaneous metastases showed the appearnce of poorly differentiated pleomorphic sarcoma. Published reports of mixed malignant lung tumours are reviewed."}
{"id": "PMID:229586", "title": "Inhibition of electrogenic sodium transport across toad urinary bladder by the mycotoxin patulin.", "content": "The effects of the mycotoxin patulin (4-hydroxy-4H-furo[3,2c]pyran-2(6H)-one) on short circuited intact toad bladder and on Na+-K+, activated ATPase were examined in an attempt to elucidate the relationship between toxin, the Na+-K+ ATPase enzyme system and associated active sodium transport. Patulin inhibited transbladder short circuit current and Na+-K+ ATPase from isolated bladder preprations. The effect was exponentially dependent on time. A significantly slower rate of inhibition was achieved within 15-30 min. The results are compatible with the assumption that Na+-K+ ATPase is associated with the pump mechanism since patulin inhibited enzyme activity and concomitantly reduced the rate of electrogenic Na+ transport. A significant correlation suggested a cause-effect relationship.", "contents": "Inhibition of electrogenic sodium transport across toad urinary bladder by the mycotoxin patulin. The effects of the mycotoxin patulin (4-hydroxy-4H-furo[3,2c]pyran-2(6H)-one) on short circuited intact toad bladder and on Na+-K+, activated ATPase were examined in an attempt to elucidate the relationship between toxin, the Na+-K+ ATPase enzyme system and associated active sodium transport. Patulin inhibited transbladder short circuit current and Na+-K+ ATPase from isolated bladder preprations. The effect was exponentially dependent on time. A significantly slower rate of inhibition was achieved within 15-30 min. The results are compatible with the assumption that Na+-K+ ATPase is associated with the pump mechanism since patulin inhibited enzyme activity and concomitantly reduced the rate of electrogenic Na+ transport. A significant correlation suggested a cause-effect relationship."}
{"id": "PMID:229587", "title": "Silicosis and fibrogenesis: fact and artifact.", "content": "Although the pulmonary and extrapulmonary manifestations of silicosis in humans have been extensively documented, the mechanisms by which the fibrogenic effects of silica are manifested remain obscure. In this review, both in vitro and in vivo models of silicosis are discussed, with emphasis on the potential methodological pitfalls of each. In animal models, for example, species variability, silica type and route of administration all effect the results obtained. Tissue culture work has provided evidence that the fibroblast-macrophage interaction is a key event in fibrogenesis. However, critical variables in experimental design make it difficult to compare the often conflicting results of different workers. Experimental conditions that directly affect collagen chain biosynthesis and subsequent hydroxylation of proline appear to be of particular importance. It is concluded that, in part because of methodological difficulties, there are insufficient data to draw firm conclusions regarding the effect of silica-exposed macrophages on collagen biosynthesis by fibroblasts in vitro; there are few, if any, data concerning the role of the macrophage that has ingested silica in human or animal models of silicosis.", "contents": "Silicosis and fibrogenesis: fact and artifact. Although the pulmonary and extrapulmonary manifestations of silicosis in humans have been extensively documented, the mechanisms by which the fibrogenic effects of silica are manifested remain obscure. In this review, both in vitro and in vivo models of silicosis are discussed, with emphasis on the potential methodological pitfalls of each. In animal models, for example, species variability, silica type and route of administration all effect the results obtained. Tissue culture work has provided evidence that the fibroblast-macrophage interaction is a key event in fibrogenesis. However, critical variables in experimental design make it difficult to compare the often conflicting results of different workers. Experimental conditions that directly affect collagen chain biosynthesis and subsequent hydroxylation of proline appear to be of particular importance. It is concluded that, in part because of methodological difficulties, there are insufficient data to draw firm conclusions regarding the effect of silica-exposed macrophages on collagen biosynthesis by fibroblasts in vitro; there are few, if any, data concerning the role of the macrophage that has ingested silica in human or animal models of silicosis."}
{"id": "PMID:229588", "title": "Urinary excretion of estrone glucosiduronate, 17 beta-estradiol-17-glucosiduronate, and estriol-16 alpha-glucosiduronate. Significance of proportionate differences during the menstrual cycle.", "content": "The urinary excretion of estrone glucosiduronate, 17 beta-estradiol-17-glucosiduronate, and estriol-16 alpha-glucosiduronate in men and throughout the menstrual cycle in women was measured by specific radioimmunoassay. In 9 men the mean +/- SE excretion of these conjugates was 15.9 +/- 1.4, 2.7 +/- 0.3, and 3.2 +/- 0.2 microgram/24 h respectively. In 15 women studied in the midfollicular phase (day 8) of the menstrual cycle, the excretion was 19.4 +/- 1.7, 2.9 +/- 0.2, and 5.4 +/- 1.3 micrograms/24 h. Excretion of each conjugate was significantly (P less than 0.01) elevated in the midluteal phase (day 22) to 41.9 +/- 3.9, 6.3 +/- 0.8, and 12.2 +/- 1.5 micrograms/24 h respectively (n = 14). The mean excretion of estriol-16 alpha-glucosiduronate was greater than that of 17 beta-estradiol-17-glucosiduronate in the luteal phase (P less than 0.05) but not in the follicular phase or in men (P greater than 0.05). The excretion of each of these specific conjugates measured throughout the menstrual cycle in 7 women was characterized by a sharp midcycle peak and a lower, broader luteal phase peak. The ratios of estriol-16 alpha-glucosiduronate to 17 beta-estradiol-17-glucosiduronate, estrone glucosiduronate to 17 beta-estradiol-17-glucosiduronate, and estriol-16 alpha-glucosiduronate to estrone glucosiduronate throughout the menstrual cycle were analyzed. When the mean ratio during the follicular phase was set at 1, a significant increase (P less than 0.01) occurred in the mean luteal phase ratio in each case: 1.00 +/- 0.03 to 1.66 +/- 0.09, 1.00 +/- 0.04 to 1.30 +/- 0.04, and 1.00 +/- 0.03 to 1.24 +/- 0.04 (mean +/- SE) respectively. The marked alteration in the proportions of these urinary estrogen conjugates may be due to altered metabolism of 17 beta-estradiol, but it more likely reflects a change in the pattern of estrogen secretion or production between the two phases of the menstrual cycle.", "contents": "Urinary excretion of estrone glucosiduronate, 17 beta-estradiol-17-glucosiduronate, and estriol-16 alpha-glucosiduronate. Significance of proportionate differences during the menstrual cycle. The urinary excretion of estrone glucosiduronate, 17 beta-estradiol-17-glucosiduronate, and estriol-16 alpha-glucosiduronate in men and throughout the menstrual cycle in women was measured by specific radioimmunoassay. In 9 men the mean +/- SE excretion of these conjugates was 15.9 +/- 1.4, 2.7 +/- 0.3, and 3.2 +/- 0.2 microgram/24 h respectively. In 15 women studied in the midfollicular phase (day 8) of the menstrual cycle, the excretion was 19.4 +/- 1.7, 2.9 +/- 0.2, and 5.4 +/- 1.3 micrograms/24 h. Excretion of each conjugate was significantly (P less than 0.01) elevated in the midluteal phase (day 22) to 41.9 +/- 3.9, 6.3 +/- 0.8, and 12.2 +/- 1.5 micrograms/24 h respectively (n = 14). The mean excretion of estriol-16 alpha-glucosiduronate was greater than that of 17 beta-estradiol-17-glucosiduronate in the luteal phase (P less than 0.05) but not in the follicular phase or in men (P greater than 0.05). The excretion of each of these specific conjugates measured throughout the menstrual cycle in 7 women was characterized by a sharp midcycle peak and a lower, broader luteal phase peak. The ratios of estriol-16 alpha-glucosiduronate to 17 beta-estradiol-17-glucosiduronate, estrone glucosiduronate to 17 beta-estradiol-17-glucosiduronate, and estriol-16 alpha-glucosiduronate to estrone glucosiduronate throughout the menstrual cycle were analyzed. When the mean ratio during the follicular phase was set at 1, a significant increase (P less than 0.01) occurred in the mean luteal phase ratio in each case: 1.00 +/- 0.03 to 1.66 +/- 0.09, 1.00 +/- 0.04 to 1.30 +/- 0.04, and 1.00 +/- 0.03 to 1.24 +/- 0.04 (mean +/- SE) respectively. The marked alteration in the proportions of these urinary estrogen conjugates may be due to altered metabolism of 17 beta-estradiol, but it more likely reflects a change in the pattern of estrogen secretion or production between the two phases of the menstrual cycle."}
{"id": "PMID:229589", "title": "Dexamethasone suppressibility of plasma pregnenolone or dehydroepiandrosterone in gonadectomized patients.", "content": "The 9 AM dexamethasone suppression test was carried out in gonadectomized patients, and plasma pregnenolone or dehydroepiandrosterone (DHA) was radioimmunoassayed following various amounts of dexamethasone administration. Pregnenolone, as well as the plasma ACTH level, was completely suppressed with 1 mg dexamethasone, whereas 4 mg or 8 mg of dexamethasone was needed to induce a complete DHA suppression. These findings suggest that the gonads alone contribute to the poor dexamethasone suppressibility of pregnenolone in normal subjects, and that adrenal DHA secretion might be also regulated by an unidentified factor other than ACTH, which would be suppressed with large doses of dexamethasone.", "contents": "Dexamethasone suppressibility of plasma pregnenolone or dehydroepiandrosterone in gonadectomized patients. The 9 AM dexamethasone suppression test was carried out in gonadectomized patients, and plasma pregnenolone or dehydroepiandrosterone (DHA) was radioimmunoassayed following various amounts of dexamethasone administration. Pregnenolone, as well as the plasma ACTH level, was completely suppressed with 1 mg dexamethasone, whereas 4 mg or 8 mg of dexamethasone was needed to induce a complete DHA suppression. These findings suggest that the gonads alone contribute to the poor dexamethasone suppressibility of pregnenolone in normal subjects, and that adrenal DHA secretion might be also regulated by an unidentified factor other than ACTH, which would be suppressed with large doses of dexamethasone."}
{"id": "PMID:229590", "title": "Estrone sulfate and dehydroepiandrosterone sulfate concentrations in normal subjects and men with cirrhosis.", "content": "Circulation levels of estrone sulfate (E1S) and dehydroepiandrosterone sulfate (DHAS) have been measured in plasma using a radioimmunoassay for estrone and dehydroepiandrosterone following extraction and hydrolysis of the sulfate. The mean +/- SE concentrations of E1S and DHAS in normal men were 458 +/- 25 pg/ml and 1.45 +/- 0.19 micrograms/ml, respectively. In normal women the values for days 5-7 of the cycle were 880 +/- 117 pg/ml and 1.25 +/- 0.12 micrograms/ml which were not different than the values for days 20-22 of 1195 +/- 176 pg/ml and 1.58 +/- 0.29 micrograms/ml. The mean values in post-menopausal women were 250 +/- 33 pg/ml and 0.47 +/- 0.07 micrograms/ml, both lower than the values in young women. In a group of cirrhotic men the mean values were 325 +/- 55 pg/ml and 0.38 +/- 0.12 micrograms/ml, both significantly lower than the normal values. This suggests a defect in sulfurylation in men with hepatic cirrhosis.", "contents": "Estrone sulfate and dehydroepiandrosterone sulfate concentrations in normal subjects and men with cirrhosis. Circulation levels of estrone sulfate (E1S) and dehydroepiandrosterone sulfate (DHAS) have been measured in plasma using a radioimmunoassay for estrone and dehydroepiandrosterone following extraction and hydrolysis of the sulfate. The mean +/- SE concentrations of E1S and DHAS in normal men were 458 +/- 25 pg/ml and 1.45 +/- 0.19 micrograms/ml, respectively. In normal women the values for days 5-7 of the cycle were 880 +/- 117 pg/ml and 1.25 +/- 0.12 micrograms/ml which were not different than the values for days 20-22 of 1195 +/- 176 pg/ml and 1.58 +/- 0.29 micrograms/ml. The mean values in post-menopausal women were 250 +/- 33 pg/ml and 0.47 +/- 0.07 micrograms/ml, both lower than the values in young women. In a group of cirrhotic men the mean values were 325 +/- 55 pg/ml and 0.38 +/- 0.12 micrograms/ml, both significantly lower than the normal values. This suggests a defect in sulfurylation in men with hepatic cirrhosis."}
{"id": "PMID:229591", "title": "[Phosphonates and their importance for dental practice].", "content": "In the light of a literature review, the author deals with the significance of anorganic pyrophosphate in the mineralization process in the organism. Diphosphonates are synthetic substances which act on mineralisation. The author made experiments with them, the results of which might be of importance in the stomatological sphere with regard to caries reduction and plaque inhibition.", "contents": "[Phosphonates and their importance for dental practice]. In the light of a literature review, the author deals with the significance of anorganic pyrophosphate in the mineralization process in the organism. Diphosphonates are synthetic substances which act on mineralisation. The author made experiments with them, the results of which might be of importance in the stomatological sphere with regard to caries reduction and plaque inhibition."}
{"id": "PMID:229592", "title": "Effect of primary and recurrent cytomegalovirus infections upon graft and patient survival after renal transplantation.", "content": "One hundred sixty-four patients were prospectively studied for evidence of cytomegalovirus (CMV) infection after renal transplantation to determine the effect of primary and recurrent CMV infection on early graft and patient survival. Primary infections occurred in 62% (21 of 34) of pretransplant seronegative recipients and recurrent infection infection in 93% (121 of 130) of seropositive recipients. Symptomatic infections occurred in 81% (17 of 21) of primarily infected and 31% (37 of 121) of recurrently infected recipients. CMV infections (determined by initial virus excretion) occurred in 86% of the primarily infected and 96% of the recurrently infected symptomatic recipients by the 9th post-transplant week. In contrast, only 53% of nonsymptomatic recipients excrete virus by the 9th week. Primarily infected recipients experienced a significantly lower graft survival at 6 months than uninfected seronegative or recurrently infected patients. However, there was no significant difference in patient or graft survival at 1 year. Recipients who developed recurrent symptomatic infections had a significantly lower graft and patient survival than those recipients who developed nonsymptomatic recurrent infections (P less than 0.0002 patient survival and P less than 0.001 graft survival at 12 months).", "contents": "Effect of primary and recurrent cytomegalovirus infections upon graft and patient survival after renal transplantation. One hundred sixty-four patients were prospectively studied for evidence of cytomegalovirus (CMV) infection after renal transplantation to determine the effect of primary and recurrent CMV infection on early graft and patient survival. Primary infections occurred in 62% (21 of 34) of pretransplant seronegative recipients and recurrent infection infection in 93% (121 of 130) of seropositive recipients. Symptomatic infections occurred in 81% (17 of 21) of primarily infected and 31% (37 of 121) of recurrently infected recipients. CMV infections (determined by initial virus excretion) occurred in 86% of the primarily infected and 96% of the recurrently infected symptomatic recipients by the 9th post-transplant week. In contrast, only 53% of nonsymptomatic recipients excrete virus by the 9th week. Primarily infected recipients experienced a significantly lower graft survival at 6 months than uninfected seronegative or recurrently infected patients. However, there was no significant difference in patient or graft survival at 1 year. Recipients who developed recurrent symptomatic infections had a significantly lower graft and patient survival than those recipients who developed nonsymptomatic recurrent infections (P less than 0.0002 patient survival and P less than 0.001 graft survival at 12 months)."}
{"id": "PMID:229593", "title": "Cytomegalovirus infection blocks the beneficial effect of pretransplant blood transfusion on renal allograft survival.", "content": "Two factors which have gained attention as possible contributors to success of renal allografts are freedom from infection with cytomegalovirus (CMV) after transplant and administration of multiple blood transfusions pretransplant. In order to determine the interrelationship of these two variables, we analyzed 55 recipients of well matched (at least two antigens) cadaveric kidneys. In this study, absence of CMV infection and receipt of multiple transfusions both provided favorable outcomes. When patients were grouped by both factors, those who were free of infection and received multiple transfusions did significantly better than any other combination. Infection with CMV decreased the frequency of allograft survival in multiply transfused patients to a point intermediate between the above group and those who had not been multiply transfused. Since CMV infection can be predicted by measurements made pretransplant, and since up to one-quarter of CMV infection which develops post-transplant is transmitted with the allograft, administration of multiple transfusion to all patients and the use of donors who are free of latent CMV infection for CMV antibody-negative potential recipients should increase allograft success. For those potential recipients who already have latent CMV infection, further study will be necessary to determine what stimuli can be given pretransplant to prevent the interference with the beneficial effect of multiple transfusion.", "contents": "Cytomegalovirus infection blocks the beneficial effect of pretransplant blood transfusion on renal allograft survival. Two factors which have gained attention as possible contributors to success of renal allografts are freedom from infection with cytomegalovirus (CMV) after transplant and administration of multiple blood transfusions pretransplant. In order to determine the interrelationship of these two variables, we analyzed 55 recipients of well matched (at least two antigens) cadaveric kidneys. In this study, absence of CMV infection and receipt of multiple transfusions both provided favorable outcomes. When patients were grouped by both factors, those who were free of infection and received multiple transfusions did significantly better than any other combination. Infection with CMV decreased the frequency of allograft survival in multiply transfused patients to a point intermediate between the above group and those who had not been multiply transfused. Since CMV infection can be predicted by measurements made pretransplant, and since up to one-quarter of CMV infection which develops post-transplant is transmitted with the allograft, administration of multiple transfusion to all patients and the use of donors who are free of latent CMV infection for CMV antibody-negative potential recipients should increase allograft success. For those potential recipients who already have latent CMV infection, further study will be necessary to determine what stimuli can be given pretransplant to prevent the interference with the beneficial effect of multiple transfusion."}
{"id": "PMID:229594", "title": "Prospective study of the prevalence and symptomatology of cytomegalovirus infection in renal transplant recipients.", "content": "To determine the incidence and symptomatology of cytomegalovirus (CMV) infection in renal transplant recipients, we followed 40 patients prospectively for 5 to 24 months after operation. As judged by the serological change and virus isolation from blood and/or urine, the infection rate for the entire group was 82% (33 of 40 patients). Two types of infection were recognized: primary infection that occurred in 3 patients, and reactivation infection that occurred in 30 patients. Twenty-one patients were asymptomatic and 12 were mildly symptomatic. Four had mild hepatic dysfunction; two had the CMV mononucleosis syndrome associated with mild to moderate deterioration of renal function. Two patients had hyperglycemia. One patient who reached a CMV antibody titer of 1:32,768 was totally asymptomatic other than fever of short duration. CMV-induced pneumonitis or retinitis was not noted, and there was no mortality from CMV infection in our patients. Factors which may be associated with the absence of severe manifestations of active CMV infection in these patients are discussed.", "contents": "Prospective study of the prevalence and symptomatology of cytomegalovirus infection in renal transplant recipients. To determine the incidence and symptomatology of cytomegalovirus (CMV) infection in renal transplant recipients, we followed 40 patients prospectively for 5 to 24 months after operation. As judged by the serological change and virus isolation from blood and/or urine, the infection rate for the entire group was 82% (33 of 40 patients). Two types of infection were recognized: primary infection that occurred in 3 patients, and reactivation infection that occurred in 30 patients. Twenty-one patients were asymptomatic and 12 were mildly symptomatic. Four had mild hepatic dysfunction; two had the CMV mononucleosis syndrome associated with mild to moderate deterioration of renal function. Two patients had hyperglycemia. One patient who reached a CMV antibody titer of 1:32,768 was totally asymptomatic other than fever of short duration. CMV-induced pneumonitis or retinitis was not noted, and there was no mortality from CMV infection in our patients. Factors which may be associated with the absence of severe manifestations of active CMV infection in these patients are discussed."}
{"id": "PMID:229596", "title": "[Dynamics of the spreading of normal and transformed hamster cells].", "content": "Morphological peculiarities of spreading studied by scanning electron microscopy in two lines of transformed hamster fibroblasts (HETR and HEC--40) were compared to the normal hamster embryo fibroblasts (NHG). The surface of spherical not streading cells was of a mixed type microrelief (small blebs and microvilli). In transformed cells, the microvillous component was more developed than in their normal counterparts. During cell spreading distinct differences were observed between normal and transformed cells in their cell surface contact interaction with solid substratum. NHF cells formed a well-developed concentrically disposed thin lamelloplasm, while HEC-40 cells had asimmetrically disposed lamelloplasm in combination with long filopodia and HETR cells had a rather thick lamelloplasm consisting of several fragments (often forming star-like pattern). At the polarization stage of spreading neither HETR nor HEC-40 reached the same degree of spreading and flattening as NHF. Moreover, the dorsal surface of transformed cells had a complex microrelief in contrast to a rather smooth surface of NHF. These results are discussed in connection with earlier results on spreading of normal and transformed mouse fibroblasts.", "contents": "[Dynamics of the spreading of normal and transformed hamster cells]. Morphological peculiarities of spreading studied by scanning electron microscopy in two lines of transformed hamster fibroblasts (HETR and HEC--40) were compared to the normal hamster embryo fibroblasts (NHG). The surface of spherical not streading cells was of a mixed type microrelief (small blebs and microvilli). In transformed cells, the microvillous component was more developed than in their normal counterparts. During cell spreading distinct differences were observed between normal and transformed cells in their cell surface contact interaction with solid substratum. NHF cells formed a well-developed concentrically disposed thin lamelloplasm, while HEC-40 cells had asimmetrically disposed lamelloplasm in combination with long filopodia and HETR cells had a rather thick lamelloplasm consisting of several fragments (often forming star-like pattern). At the polarization stage of spreading neither HETR nor HEC-40 reached the same degree of spreading and flattening as NHF. Moreover, the dorsal surface of transformed cells had a complex microrelief in contrast to a rather smooth surface of NHF. These results are discussed in connection with earlier results on spreading of normal and transformed mouse fibroblasts."}
{"id": "PMID:229597", "title": "[Effect of a viral infection on the cellular chromosome apparatus of mice in vitro and in vivo against a background of hydrocortisone action].", "content": "A cytogenetic investigation of murine bone marrow after hydrocortison injection has been made. High doses of hormone (50 mg/kg) provoke deteriorations in bone marrow both in the structure and in the chromosome number. A dose of 5 mg/kg has no such effect. The Koksak A13 virus does not induce cytogenetic deteriorations in mice, however, it is able to produce a big mutagenic effect on the hydrocortison background. The vaccine strain of measles virus -- Leningrad-16 -- also increases its mutagenic action on the bone marrow cell chromsome apparatus of mice affected with hydrocortison. At the same time, in the cell culture of murine kidney, hydrocortison does not induce chromosome deteriorations and even lowers the frequency of cells with deteriorations in the chromosome set during the initial days after injecting the virus culture with measles virus.", "contents": "[Effect of a viral infection on the cellular chromosome apparatus of mice in vitro and in vivo against a background of hydrocortisone action]. A cytogenetic investigation of murine bone marrow after hydrocortison injection has been made. High doses of hormone (50 mg/kg) provoke deteriorations in bone marrow both in the structure and in the chromosome number. A dose of 5 mg/kg has no such effect. The Koksak A13 virus does not induce cytogenetic deteriorations in mice, however, it is able to produce a big mutagenic effect on the hydrocortison background. The vaccine strain of measles virus -- Leningrad-16 -- also increases its mutagenic action on the bone marrow cell chromsome apparatus of mice affected with hydrocortison. At the same time, in the cell culture of murine kidney, hydrocortison does not induce chromosome deteriorations and even lowers the frequency of cells with deteriorations in the chromosome set during the initial days after injecting the virus culture with measles virus."}
{"id": "PMID:229598", "title": "Ultrastructural study of leukemic cell phagocytosis using the myeloperoxidase reaction.", "content": "The phagocytosis (in the absence of serum factors) of zymosan particles by peripheral leukocytes isolated from ten patients with acute leukemia (AMbL, AMoL, AMML, AUL, ALL and CML-BC) was studied at the electron microscope. An evident phagocytic activity was observed only in the cells in which cytochemical and ultrastructural features suggested that the blast elements belonged to the monocytic series. However, no phagocytosis by unclassifiable leukemic blasts was observed, even though they had some submicroscopic characteristics of the monocytic series. These findings suggest that phagocytic capacity develops during the course of cell differentiation, becoming striking only when the blast cell acquires the ultrastructural features of the pro-monocytic stage. Using the myeloperoxidase reaction, this study also demonstrates a morphological alteration in the degranulation process after the ingestion of zymosan particles in both the blasts and the mature PMN cells of leukemic patients. This defect could be related to the susceptibility to severe infections usually found in subjects with hematological malignancies.", "contents": "Ultrastructural study of leukemic cell phagocytosis using the myeloperoxidase reaction. The phagocytosis (in the absence of serum factors) of zymosan particles by peripheral leukocytes isolated from ten patients with acute leukemia (AMbL, AMoL, AMML, AUL, ALL and CML-BC) was studied at the electron microscope. An evident phagocytic activity was observed only in the cells in which cytochemical and ultrastructural features suggested that the blast elements belonged to the monocytic series. However, no phagocytosis by unclassifiable leukemic blasts was observed, even though they had some submicroscopic characteristics of the monocytic series. These findings suggest that phagocytic capacity develops during the course of cell differentiation, becoming striking only when the blast cell acquires the ultrastructural features of the pro-monocytic stage. Using the myeloperoxidase reaction, this study also demonstrates a morphological alteration in the degranulation process after the ingestion of zymosan particles in both the blasts and the mature PMN cells of leukemic patients. This defect could be related to the susceptibility to severe infections usually found in subjects with hematological malignancies."}
{"id": "PMID:229599", "title": "Early detection of ductal breast cancer: the diagnostic procedure for grouped microcalcifications.", "content": "Mammography and xeroradiography for grouped microcalcifications are considered the most effective diagnostic methods to detect occult breast carcinoma. Radiography must direct the surgeon to excise the nonpalpable area. The removal of the tissue with grouped microcalcifications must be confirmed by intraoperative radiological control. The histologic preparation must be guided by radiographic controls. Tissue with calcific deposits is examined by step sections. The diagnostic success depends upon the cooperation between the radiologist, the surgeon, and the pathologist. Our results from 1964 to 1977 have shown a frequency of 14.4% of occult carcinoma. Ductal or lobular carcinomata in situ have been diagnosed in 8.9%. In 9.9% of the patients, cystic disease with severe and atypical proliferations has been encountered.", "contents": "Early detection of ductal breast cancer: the diagnostic procedure for grouped microcalcifications. Mammography and xeroradiography for grouped microcalcifications are considered the most effective diagnostic methods to detect occult breast carcinoma. Radiography must direct the surgeon to excise the nonpalpable area. The removal of the tissue with grouped microcalcifications must be confirmed by intraoperative radiological control. The histologic preparation must be guided by radiographic controls. Tissue with calcific deposits is examined by step sections. The diagnostic success depends upon the cooperation between the radiologist, the surgeon, and the pathologist. Our results from 1964 to 1977 have shown a frequency of 14.4% of occult carcinoma. Ductal or lobular carcinomata in situ have been diagnosed in 8.9%. In 9.9% of the patients, cystic disease with severe and atypical proliferations has been encountered."}
{"id": "PMID:229600", "title": "Early detection of ductal breast cancer: the diagnostic procedure for pathological discharge from the nipple.", "content": "Pathologic discharge from the nipple may be the only symptom of an early stage of carcinoma. Galactography is then the diagnostic method of choice to locate intraductal, nonpalpable lesions. The technique of galactography, the adequate surgical approach of pathologic galactographs (milk-duct segment resection), and the appropriate histological work-up of the surgical specimen are demonstrated. We report on 1918 galactographies in 1363 women with pathological discharge. In only 427 cases was a milk duct segment resection necessary (31.4%). In 8.5%, we found invasive intraductal cancer and in 2.9% ductal carcinomata in situ. Only 1 patient with breast cancer had axillary metastases. Extensive intraductal solid, papillary or adenomatous proliferations were found in 11.9% of the patients with excision. In 46.7% of the patients, papillomas were excised, a definitive treatment for this process. The supposition for success in the early diagnosis of cancer is close teamwork among the radiology, surgery and pathology services: the diagnostic result depends upon this. We attribute our yield of exact diagnosis to a very sophisticated histological work-up. We believe that this is necessary to avoid diagnostic failures.", "contents": "Early detection of ductal breast cancer: the diagnostic procedure for pathological discharge from the nipple. Pathologic discharge from the nipple may be the only symptom of an early stage of carcinoma. Galactography is then the diagnostic method of choice to locate intraductal, nonpalpable lesions. The technique of galactography, the adequate surgical approach of pathologic galactographs (milk-duct segment resection), and the appropriate histological work-up of the surgical specimen are demonstrated. We report on 1918 galactographies in 1363 women with pathological discharge. In only 427 cases was a milk duct segment resection necessary (31.4%). In 8.5%, we found invasive intraductal cancer and in 2.9% ductal carcinomata in situ. Only 1 patient with breast cancer had axillary metastases. Extensive intraductal solid, papillary or adenomatous proliferations were found in 11.9% of the patients with excision. In 46.7% of the patients, papillomas were excised, a definitive treatment for this process. The supposition for success in the early diagnosis of cancer is close teamwork among the radiology, surgery and pathology services: the diagnostic result depends upon this. We attribute our yield of exact diagnosis to a very sophisticated histological work-up. We believe that this is necessary to avoid diagnostic failures."}
{"id": "PMID:229602", "title": "Lobectomy with bronchoplastic procedures for lung cancer.", "content": "From April 1970 to October 1977, 19 patients with lung cancer of the upper lobar bronchus orifice underwent radical lobectomy with major bronchus resection. Sleeve lobectomy was accomplished in 11 cases and wedge lobectomy in the remaining 8. The length of the free bronchial margin in the surgical specimen was less than 1 cm in 3 cases, but limited pulmonary reserve did not allow pneumonectomy. Squamous carcinoma was diagnosed in 14 patients, adenocarcinoma in 2, oat-cell carcinoma in 2, and large cell carcinoma in one. Most cases (70%) were pathological stage I. There was one operative death due to anastomotic leakage (5%), and another patient required pneumonectomy completion. Of 13 patients with non oat-cell carcinoma and adequate bronchial resection, none had local recurrence: 3 patients developed distant metastases, and 10 are alive and disease-free after a follow-up period ranging from 16 to 104 months. The authors conclude that in selected lung cancer patients lobectomy with bronchoplastic procedures is superior to pneumonectomy for tissue sparing advantages.", "contents": "Lobectomy with bronchoplastic procedures for lung cancer. From April 1970 to October 1977, 19 patients with lung cancer of the upper lobar bronchus orifice underwent radical lobectomy with major bronchus resection. Sleeve lobectomy was accomplished in 11 cases and wedge lobectomy in the remaining 8. The length of the free bronchial margin in the surgical specimen was less than 1 cm in 3 cases, but limited pulmonary reserve did not allow pneumonectomy. Squamous carcinoma was diagnosed in 14 patients, adenocarcinoma in 2, oat-cell carcinoma in 2, and large cell carcinoma in one. Most cases (70%) were pathological stage I. There was one operative death due to anastomotic leakage (5%), and another patient required pneumonectomy completion. Of 13 patients with non oat-cell carcinoma and adequate bronchial resection, none had local recurrence: 3 patients developed distant metastases, and 10 are alive and disease-free after a follow-up period ranging from 16 to 104 months. The authors conclude that in selected lung cancer patients lobectomy with bronchoplastic procedures is superior to pneumonectomy for tissue sparing advantages."}
{"id": "PMID:229603", "title": "Unusual morphologic features of a primary liver neoplasm.", "content": "Light and electron microscopy study of an unusual primary liver neoplasm observed in a 36-year-old woman. By light microscopy the tumor, initially detected by a needle biopsy and later surgically removed, was mainly composed of spindle-shaped and multinucleated cells which were similar to rhabdomyoblasts. These cells, however, showed ultrastructural features of hepatocytes.", "contents": "Unusual morphologic features of a primary liver neoplasm. Light and electron microscopy study of an unusual primary liver neoplasm observed in a 36-year-old woman. By light microscopy the tumor, initially detected by a needle biopsy and later surgically removed, was mainly composed of spindle-shaped and multinucleated cells which were similar to rhabdomyoblasts. These cells, however, showed ultrastructural features of hepatocytes."}
{"id": "PMID:229605", "title": "[Physicochemical and kinetic characteristics of myeloperoxidase of cow neutrophilic leucocytes].", "content": "Myeloperoxidase (MPO) isolated from granular fraction of cow peritoneal neutrophils had the RZ value equalled to 0.79. The absorption spectrum of MPO possesses characteristic bands at 430, 500, 570, 625, 690 nm. The molecular weight and sedimentation constant of the enzyme are 135.000-140.000 Daltons and 7.9S, respectively. The data obtained demonstrate the high thermostable property of MPO. Investigations of the pH optimum and effects of varying H2O2, o-dianizidine and MPO concentrations are described.", "contents": "[Physicochemical and kinetic characteristics of myeloperoxidase of cow neutrophilic leucocytes]. Myeloperoxidase (MPO) isolated from granular fraction of cow peritoneal neutrophils had the RZ value equalled to 0.79. The absorption spectrum of MPO possesses characteristic bands at 430, 500, 570, 625, 690 nm. The molecular weight and sedimentation constant of the enzyme are 135.000-140.000 Daltons and 7.9S, respectively. The data obtained demonstrate the high thermostable property of MPO. Investigations of the pH optimum and effects of varying H2O2, o-dianizidine and MPO concentrations are described."}
{"id": "PMID:229606", "title": "[Activity of certain redox enzymes of rat liver mitochondria at different levels of dietary vitamin E].", "content": "Taking into account the found earlier relation of vitamin E to the ubiquinone functioning and metabolism, the authors studied the enzymic activity of succinate dehydrogenase, NADH-dehydrogenase and cytochrome-c-oxidase--coenzyme Q binding sites of the respiratory chain of the rat liver mitochondria. The experiments were carried out with female rats who received a vitamin-E-deficient diet for 6 months. The enzymic activities and the ubiquinone content in the liver mitochondria of these animals are shown to be considerably lower as compared to the animals received a vitamin E diet; alpha-ocopherol, alpha-tocopheronolactone and ubiquinone 3h after administration manifest a clearly pronounced normalizing effect relative to both the enzymic activity and the ubiquinone content. An assumption is advanced that the effect of alpha-tocopherol and its metabolite is associated with controlling the level of functionally active ubiquinone in the mitochondria. Other mechanisms of the membrane-bound enzymes control by the compounds under study are also discussed in connection with the alpha-tocopherol effect on the mitochondrial membranes.", "contents": "[Activity of certain redox enzymes of rat liver mitochondria at different levels of dietary vitamin E]. Taking into account the found earlier relation of vitamin E to the ubiquinone functioning and metabolism, the authors studied the enzymic activity of succinate dehydrogenase, NADH-dehydrogenase and cytochrome-c-oxidase--coenzyme Q binding sites of the respiratory chain of the rat liver mitochondria. The experiments were carried out with female rats who received a vitamin-E-deficient diet for 6 months. The enzymic activities and the ubiquinone content in the liver mitochondria of these animals are shown to be considerably lower as compared to the animals received a vitamin E diet; alpha-ocopherol, alpha-tocopheronolactone and ubiquinone 3h after administration manifest a clearly pronounced normalizing effect relative to both the enzymic activity and the ubiquinone content. An assumption is advanced that the effect of alpha-tocopherol and its metabolite is associated with controlling the level of functionally active ubiquinone in the mitochondria. Other mechanisms of the membrane-bound enzymes control by the compounds under study are also discussed in connection with the alpha-tocopherol effect on the mitochondrial membranes."}
{"id": "PMID:229618", "title": "[Use of a selective sulfite-reducing medium for the isolation of Clostridium perfringens].", "content": "The effect of sulphite-reduction in 33 sample bacterial strains  was tested. With regard to the capacity of reducing sulphite in modified sulphite-reduction media in a wide scale of bacterial strains the possibility of an application of selective media with an addition of various concentrations of antibiotic solutions was checked. A concentration of 750 microgram of D-cycloserine per 1 ml of the sulphite-reduction medium appeared to be the most advantageous for the isolation and detection of sulphite-reductive clostridia, above all of Clostridium perfringens. This concentration ensured also a sufficient inhibition of undesirable bacteria without any affection of the growth and capacity of Clostridium perfringens to reduce sulphite in the applied medium.", "contents": "[Use of a selective sulfite-reducing medium for the isolation of Clostridium perfringens]. The effect of sulphite-reduction in 33 sample bacterial strains  was tested. With regard to the capacity of reducing sulphite in modified sulphite-reduction media in a wide scale of bacterial strains the possibility of an application of selective media with an addition of various concentrations of antibiotic solutions was checked. A concentration of 750 microgram of D-cycloserine per 1 ml of the sulphite-reduction medium appeared to be the most advantageous for the isolation and detection of sulphite-reductive clostridia, above all of Clostridium perfringens. This concentration ensured also a sufficient inhibition of undesirable bacteria without any affection of the growth and capacity of Clostridium perfringens to reduce sulphite in the applied medium."}
{"id": "PMID:229619", "title": "[The effect of halothane anesthesia on the function of the adrenal cortex and some metabolites in the blood plasma of pigs not susceptible to malignant hyperthermia].", "content": "The effects were investigated of a 25-minute inhalation of halothane with oxygen on three to four months old pigs of the Large White breed. Symptoms of malignant hyperthermia did not occur. The actual total anesthesia, which causes slight hypoproteinemia, hypoglycemia and hypocholesterolemia without significant changes in the content of non-esterified fatty acids (NEFA) and urea, induced only a  slight increase of circulating 11-hydroxycorticosteroids (11-OHCS). The combination of anesthesia with castration of gilts or barrows significantly increased the concentration of 11-OHCS but did not reach the level recorded after the application of ACTH. The higher levels of 11-OHCS were accompanied by higher concentrations of NEFA and glucose. The treatment of the animals lasting half an hour prior to inhalation of halothane at maximum doses or one hour in the control unanesthetized pigs produced an effect, mainly on the 11-OHCS concentration and on the activity of creatine kinase in the plasma. The results indicate that the adrenocortical response to the effect of halothane is not stronger than the response to simple handling connected with excitement and muscular activity of the animals. Therefore there is no reason of considering halothane anesthesia as a factor causing great stress and pigs which in its course do not respond with malignant hyperthermia as animals insensitive to stress. The aptness of denotation of clinical manifestations of genetically defective muscles in pigs is discussed.", "contents": "[The effect of halothane anesthesia on the function of the adrenal cortex and some metabolites in the blood plasma of pigs not susceptible to malignant hyperthermia]. The effects were investigated of a 25-minute inhalation of halothane with oxygen on three to four months old pigs of the Large White breed. Symptoms of malignant hyperthermia did not occur. The actual total anesthesia, which causes slight hypoproteinemia, hypoglycemia and hypocholesterolemia without significant changes in the content of non-esterified fatty acids (NEFA) and urea, induced only a  slight increase of circulating 11-hydroxycorticosteroids (11-OHCS). The combination of anesthesia with castration of gilts or barrows significantly increased the concentration of 11-OHCS but did not reach the level recorded after the application of ACTH. The higher levels of 11-OHCS were accompanied by higher concentrations of NEFA and glucose. The treatment of the animals lasting half an hour prior to inhalation of halothane at maximum doses or one hour in the control unanesthetized pigs produced an effect, mainly on the 11-OHCS concentration and on the activity of creatine kinase in the plasma. The results indicate that the adrenocortical response to the effect of halothane is not stronger than the response to simple handling connected with excitement and muscular activity of the animals. Therefore there is no reason of considering halothane anesthesia as a factor causing great stress and pigs which in its course do not respond with malignant hyperthermia as animals insensitive to stress. The aptness of denotation of clinical manifestations of genetically defective muscles in pigs is discussed."}
{"id": "PMID:229633", "title": "[Modern concepts of the metabolism and genetic polymorphism of collagen (a review)].", "content": "The data on structure, biosynthesis, post-synthetic modifications, extracellular development and degradation of collagen are briefly reviewed. Role of main enzymes, participating in collagen turnover, is discussed. Isoforms of the protein are considered in details. The importance of studies on collagen proteins is noted in connection with investigations on morphogenesis, cell differentiation, regeneration.", "contents": "[Modern concepts of the metabolism and genetic polymorphism of collagen (a review)]. The data on structure, biosynthesis, post-synthetic modifications, extracellular development and degradation of collagen are briefly reviewed. Role of main enzymes, participating in collagen turnover, is discussed. Isoforms of the protein are considered in details. The importance of studies on collagen proteins is noted in connection with investigations on morphogenesis, cell differentiation, regeneration."}
{"id": "PMID:229638", "title": "[The protein-synthesizing apparatus in chemically- and virus-induced tumors].", "content": "The description is given of the distribution of poly(A)-containing mRNA in different subcellular fractions (nuclei, mitochondria, free- and membrane-bound polyribosomes) from the normal tissues hepatoma MD and chick Rous. The amount of poly(A)-RNA is found to increase in all tumor cell fractions, but free polysomes.", "contents": "[The protein-synthesizing apparatus in chemically- and virus-induced tumors]. The description is given of the distribution of poly(A)-containing mRNA in different subcellular fractions (nuclei, mitochondria, free- and membrane-bound polyribosomes) from the normal tissues hepatoma MD and chick Rous. The amount of poly(A)-RNA is found to increase in all tumor cell fractions, but free polysomes."}
{"id": "PMID:229634", "title": "[Regulation of Na, K-ATPase activity in the rat brain by noradrenaline].", "content": "Effect of noradrenaline on activity of Na, K-ATPase from heavy microsomes of rat brain was studied in vitro; the effect of noradrenaline was shown to be dose dependent. The maximal activation of the enzyme was observed at 5.10(-5) M concentration of the catecholamine; an increase of its concentration above 5.10(-4) M inhibited Na, K-ATPase. beta-Adrenolytic drug propranolol /1.10(-5) M/ did not affect the noradrenaline action. At the same time, an alpha-adrenolytic drug phentholamine /1.10(-5) M/ decreased down to zero the activating effect of the catecholamine, but did not affect the inhibitory effect of noradrenaline at high concentrations /1.10(-3) M/. Effects of selective alpha-adrenomimetic compound phenylephrine were also studied. The data obtained suggest that the activating effect of noradrenaline on Na, K-ATPase from rat brain is mediated through alpha-adrenoreceptors.", "contents": "[Regulation of Na, K-ATPase activity in the rat brain by noradrenaline]. Effect of noradrenaline on activity of Na, K-ATPase from heavy microsomes of rat brain was studied in vitro; the effect of noradrenaline was shown to be dose dependent. The maximal activation of the enzyme was observed at 5.10(-5) M concentration of the catecholamine; an increase of its concentration above 5.10(-4) M inhibited Na, K-ATPase. beta-Adrenolytic drug propranolol /1.10(-5) M/ did not affect the noradrenaline action. At the same time, an alpha-adrenolytic drug phentholamine /1.10(-5) M/ decreased down to zero the activating effect of the catecholamine, but did not affect the inhibitory effect of noradrenaline at high concentrations /1.10(-3) M/. Effects of selective alpha-adrenomimetic compound phenylephrine were also studied. The data obtained suggest that the activating effect of noradrenaline on Na, K-ATPase from rat brain is mediated through alpha-adrenoreceptors."}
{"id": "PMID:229635", "title": "[Characteristics of thiamine diphosphate metabolism in the liver in acute hypobaric hypoxia].", "content": "Rates of thiamin diphosphate accumulation in rat liver tissue and its subsequent depletion were decreased within the first hour after vitamin B1 administration into the animals with oxygen insufficiency. Hypoxia apparently inhibited simultaneously the processes of thiamin diphosphate biosynthesis and degradation, as a result of which content of the coenzyme was unaltered in tissues under conditions of usual intake of thiamin. The data obtained suggest that the activity of enzymes, participating in thiamin diphosphate turnover and estimated in vitro do not reflect their real functioning in the whole organism. Importance of ATP, ADP and pyridine nucleotides is considered as regulating agents of enzymes participating in thiamin diphosphate turnover under hypoxia.", "contents": "[Characteristics of thiamine diphosphate metabolism in the liver in acute hypobaric hypoxia]. Rates of thiamin diphosphate accumulation in rat liver tissue and its subsequent depletion were decreased within the first hour after vitamin B1 administration into the animals with oxygen insufficiency. Hypoxia apparently inhibited simultaneously the processes of thiamin diphosphate biosynthesis and degradation, as a result of which content of the coenzyme was unaltered in tissues under conditions of usual intake of thiamin. The data obtained suggest that the activity of enzymes, participating in thiamin diphosphate turnover and estimated in vitro do not reflect their real functioning in the whole organism. Importance of ATP, ADP and pyridine nucleotides is considered as regulating agents of enzymes participating in thiamin diphosphate turnover under hypoxia."}
{"id": "PMID:229636", "title": "[Structural characteristics of plasma lipoproteins studied with spin-labelled fatty acids].", "content": "As shown by means of electrone paramagnetic resonance of spin probes, a magnitude of ordering of lipoprotein molecular arrangement both internal and external parts of molecule was decreased in a following sequence: high density lipoproteins greater than low density greater than very low density lipoproteins. Permeability towards a reducing agent - ascorbic acid - was altered similarly in the lipoprotein surface monolayer.", "contents": "[Structural characteristics of plasma lipoproteins studied with spin-labelled fatty acids]. As shown by means of electrone paramagnetic resonance of spin probes, a magnitude of ordering of lipoprotein molecular arrangement both internal and external parts of molecule was decreased in a following sequence: high density lipoproteins greater than low density greater than very low density lipoproteins. Permeability towards a reducing agent - ascorbic acid - was altered similarly in the lipoprotein surface monolayer."}
{"id": "PMID:229640", "title": "[Breast angiography in cancer].", "content": "The roentgenological features of the blood supply of mammary glands removed for cancer are analysed. It was found that the tumor angioarchitectonics is dependent on the kind of growth and histological structure. Some angiographic changes were noted in the vascular network of the mammary gland and tumor, arising under the effect of the radical preoperative telegamma-therapy.", "contents": "[Breast angiography in cancer]. The roentgenological features of the blood supply of mammary glands removed for cancer are analysed. It was found that the tumor angioarchitectonics is dependent on the kind of growth and histological structure. Some angiographic changes were noted in the vascular network of the mammary gland and tumor, arising under the effect of the radical preoperative telegamma-therapy."}
{"id": "PMID:229645", "title": "[Changes in the indices of fat metabolism in obesity during physical activity, on a reducing diet and during meterological influences].", "content": "Clinical experimental investigations were carried out of 96 patients with light, nutritional-metabolism forms of obesity under the conditions of a moderately high mountain (1870 m above the sea level). After a treatment course of 20--25 days including: reducing diet, physical loading and cool sun-air exposure, a significant decrease of a wide spectrum of lipid indices was found, namely: total lipids, triglycerides, total cholesterol, phospholipids and beta-lipoproteins. A significant correlation was established between cholesterol decrease and beta-lipoproteins with body weight reduction over 3 kg and the high initial values of the indices. With a single physical loading in the patients with obesity -- the elevation of NEFA does not considerably differ from that of the control group with neurasthenia. The glucose loading is admitted not to indice manifested lipogenesis with the physical loading and cool sun-air exposure.", "contents": "[Changes in the indices of fat metabolism in obesity during physical activity, on a reducing diet and during meterological influences]. Clinical experimental investigations were carried out of 96 patients with light, nutritional-metabolism forms of obesity under the conditions of a moderately high mountain (1870 m above the sea level). After a treatment course of 20--25 days including: reducing diet, physical loading and cool sun-air exposure, a significant decrease of a wide spectrum of lipid indices was found, namely: total lipids, triglycerides, total cholesterol, phospholipids and beta-lipoproteins. A significant correlation was established between cholesterol decrease and beta-lipoproteins with body weight reduction over 3 kg and the high initial values of the indices. With a single physical loading in the patients with obesity -- the elevation of NEFA does not considerably differ from that of the control group with neurasthenia. The glucose loading is admitted not to indice manifested lipogenesis with the physical loading and cool sun-air exposure."}
{"id": "PMID:229641", "title": "[Effect of small amounts of methylmercury on embryogenesis and certain biochemical indices].", "content": "It was established in experiments on Wistar rats that oral methyl mercuric iodide at doses of 0.85, 0.64, 0.42 and 0.21 mg/kg daily exerts no teratogenic or embryotoxic action on the progeny. However, administration of methyl mercuric iodide at doses of 0.85 and 0.64 mg/kg produced in females a significant decrease in the SH-group content in renal and cerebral tissues, in the activity of acetylcholine esterase in the cerebellum (by 18-48%) and a rise in the activity of glucose-6-phosphatase in the kidneys (by 48-70%). The doses of 0.42 and 0.21 mg/kg administered at various periods of pregnancy, did not exert any effect on the body of females under experimental conditions. These findings are supported to a certain measure by the results of examination of a 2-month progeny of the animals given 0.21 mg/kg methyl mercuric iodide daily. The biochemical parameters of these animals did not differ from those of the control ones.", "contents": "[Effect of small amounts of methylmercury on embryogenesis and certain biochemical indices]. It was established in experiments on Wistar rats that oral methyl mercuric iodide at doses of 0.85, 0.64, 0.42 and 0.21 mg/kg daily exerts no teratogenic or embryotoxic action on the progeny. However, administration of methyl mercuric iodide at doses of 0.85 and 0.64 mg/kg produced in females a significant decrease in the SH-group content in renal and cerebral tissues, in the activity of acetylcholine esterase in the cerebellum (by 18-48%) and a rise in the activity of glucose-6-phosphatase in the kidneys (by 48-70%). The doses of 0.42 and 0.21 mg/kg administered at various periods of pregnancy, did not exert any effect on the body of females under experimental conditions. These findings are supported to a certain measure by the results of examination of a 2-month progeny of the animals given 0.21 mg/kg methyl mercuric iodide daily. The biochemical parameters of these animals did not differ from those of the control ones."}
{"id": "PMID:229646", "title": "Clinical and virologic course of herpes simplex genitalis.", "content": "The clinical and virologic course of herpes simplex genitalis in women and men was examined in order to identify measurements useful in antiviral trials. Factors influencing the clinical course included initial disease versus recurrent disease, wet-skin versus dry-skin lesions, female versus male sex. Women with initial genital herpes had higher mean peak lesion virus titers than those with recurrent disease (10(4.5) pfu compared with 10(2.5) pfu) and excreted virus longer (13 to 15 days compared with 6 to 8 days). Men with recurrent lesions had higher mean peak virus titers than women (10(4.0) pfu compared with 10(2.5) pfu), but the duration of virus excretion was shorter (three to four days compared with six to eight days). There was pronounced variation in the clinical and virologic course of recurrent lesions among different patients and even within the same patient. These observations indicate several difficulties that must be considered in conducting careful antiviral trials in patients with herpes simplex genitalis.", "contents": "Clinical and virologic course of herpes simplex genitalis. The clinical and virologic course of herpes simplex genitalis in women and men was examined in order to identify measurements useful in antiviral trials. Factors influencing the clinical course included initial disease versus recurrent disease, wet-skin versus dry-skin lesions, female versus male sex. Women with initial genital herpes had higher mean peak lesion virus titers than those with recurrent disease (10(4.5) pfu compared with 10(2.5) pfu) and excreted virus longer (13 to 15 days compared with 6 to 8 days). Men with recurrent lesions had higher mean peak virus titers than women (10(4.0) pfu compared with 10(2.5) pfu), but the duration of virus excretion was shorter (three to four days compared with six to eight days). There was pronounced variation in the clinical and virologic course of recurrent lesions among different patients and even within the same patient. These observations indicate several difficulties that must be considered in conducting careful antiviral trials in patients with herpes simplex genitalis."}
{"id": "PMID:229647", "title": "Severe neutropenia in infectious mononucleosis.", "content": "Mild neutropenia is a well-known concomitant of infectious mononucleosis caused by the Epstein-Barr virus (EBV) occurring in the first weeks of illness. However, severe neutropenia (less than 200 polymorphonuclear leukocytes per mul) is not generally regarded as a complication of infectious mononucleosis. Three patients were seen with severe neutropenia and EBV infection, and an additional eight cases were found in the literature. In two of the latter cases the neutropenia was fatal. In the 11 cases the severe neutropenia began 14 to 40 days after illness and usually lasted for three to seven days. At the time of severe neutropenia, studies of marrow specimens showed increased proportions of promyelocytes and myelocytes. Our data suggest that EBV infection is the proximate cause of the severe neutropenia in some patients with infectious mononucleosis and that in such cases close observation and early treatment of suspected superinfections is necessary.", "contents": "Severe neutropenia in infectious mononucleosis. Mild neutropenia is a well-known concomitant of infectious mononucleosis caused by the Epstein-Barr virus (EBV) occurring in the first weeks of illness. However, severe neutropenia (less than 200 polymorphonuclear leukocytes per mul) is not generally regarded as a complication of infectious mononucleosis. Three patients were seen with severe neutropenia and EBV infection, and an additional eight cases were found in the literature. In two of the latter cases the neutropenia was fatal. In the 11 cases the severe neutropenia began 14 to 40 days after illness and usually lasted for three to seven days. At the time of severe neutropenia, studies of marrow specimens showed increased proportions of promyelocytes and myelocytes. Our data suggest that EBV infection is the proximate cause of the severe neutropenia in some patients with infectious mononucleosis and that in such cases close observation and early treatment of suspected superinfections is necessary."}
{"id": "PMID:229648", "title": "[Psychosomal dwarfism with reversible growth hormone deficiency (author's transl)].", "content": "The diagnosis of psychosocial dwarfism in a 9 year-old boy with severe growth retardation (-6 1/2 standard deviations) was deduced from the typical history. The bone age was severely retarded and in the first days after admission a deficiency of growth hormone and other pituitary hormones was established. The change in environment per se led to a spontaneous reversal of the growth hormone deficiency within a short time. A rapid catch up growth was observed over the subsequent 2 1/2 years, as well as a normalisation of the psychological retardation.", "contents": "[Psychosomal dwarfism with reversible growth hormone deficiency (author's transl)]. The diagnosis of psychosocial dwarfism in a 9 year-old boy with severe growth retardation (-6 1/2 standard deviations) was deduced from the typical history. The bone age was severely retarded and in the first days after admission a deficiency of growth hormone and other pituitary hormones was established. The change in environment per se led to a spontaneous reversal of the growth hormone deficiency within a short time. A rapid catch up growth was observed over the subsequent 2 1/2 years, as well as a normalisation of the psychological retardation."}
{"id": "PMID:229649", "title": "[Diagnostic and prognostic value of scintigraphic methods in cardiology (static methods)].", "content": "The diagnostic possibilities of myocardial scintigraphy in cardiology are discussed. As an invasive technique the perfusion imaging is described. The valuation of the doubleisotope-scintigraphy for better diagnostic examination during coronary arteriography is accentuated. The 201-Thallium-scintigraphy as a non invasive method is debated. The diagnostic value of the 201-Thallium stress scintigraphy is shown. The similarity of ergometric and pharmacologic provocation with Dipyridamol is represented. In the following the reliability and the specificity of the infarct scintigraphy with 99m-Technetium-pyrophosphate as \"hot-spot-technique\" is discussed. The follow-up scintigraphy allows to draw prognostic inferences about the further course of a myocardial infarction. The scintigraphic findings were correlated to haemodynamic measurements. Scintigraphic examinations in patients with stable angina pectoris without infarction revealed correlations between the uptake of the tracer in the myocardium and a disturbed left ventricular function. A chronic deficiency in the blood supply of the myocardium is discussed as the cause of the tracer uptake.", "contents": "[Diagnostic and prognostic value of scintigraphic methods in cardiology (static methods)]. The diagnostic possibilities of myocardial scintigraphy in cardiology are discussed. As an invasive technique the perfusion imaging is described. The valuation of the doubleisotope-scintigraphy for better diagnostic examination during coronary arteriography is accentuated. The 201-Thallium-scintigraphy as a non invasive method is debated. The diagnostic value of the 201-Thallium stress scintigraphy is shown. The similarity of ergometric and pharmacologic provocation with Dipyridamol is represented. In the following the reliability and the specificity of the infarct scintigraphy with 99m-Technetium-pyrophosphate as \"hot-spot-technique\" is discussed. The follow-up scintigraphy allows to draw prognostic inferences about the further course of a myocardial infarction. The scintigraphic findings were correlated to haemodynamic measurements. Scintigraphic examinations in patients with stable angina pectoris without infarction revealed correlations between the uptake of the tracer in the myocardium and a disturbed left ventricular function. A chronic deficiency in the blood supply of the myocardium is discussed as the cause of the tracer uptake."}
{"id": "PMID:229650", "title": "[Sleep and wake-cycle as circadian rhythm (author's transl)].", "content": "Sleep-wake cycles are closely tied with the circadian period of other bodily functions. Optimal synchronization is essential for troublefree alterations of sleep and wake periods. The neurophysiologic control areas are in various of the brain are far apart from each other for which reason a great variety of possible causes for sleep difficulties do exist. It has been shown recently that spezific mono-aminergic and cholinergic systems in the brain stem do control sleep. A case study will show that it is possible to improve sleeping difficulties with the serotonin precursor L-Troyptophan.", "contents": "[Sleep and wake-cycle as circadian rhythm (author's transl)]. Sleep-wake cycles are closely tied with the circadian period of other bodily functions. Optimal synchronization is essential for troublefree alterations of sleep and wake periods. The neurophysiologic control areas are in various of the brain are far apart from each other for which reason a great variety of possible causes for sleep difficulties do exist. It has been shown recently that spezific mono-aminergic and cholinergic systems in the brain stem do control sleep. A case study will show that it is possible to improve sleeping difficulties with the serotonin precursor L-Troyptophan."}
{"id": "PMID:229653", "title": "Vasoactive intestinal polypeptide (VIP) as a mediator of the watery diarrhea syndrome.", "content": "Evidence that VIP is the principal humoral mediator of the watery diarrhea syndrome includes: (a) actions of VIP in experimental anaimals parallel the clinical manifestations of the syndrome; (b) infusions of VIP induce watery diarrhea in intestinal loops of dogs and a picture resembling the clinical syndrome in pigs, at circulating levels of the peptide similar to those observed in human disease; (c) most patients with the watery diarrhea syndrome and underlying tumors have elevated plasma levels of VIP; (d) in those patients in whom pre- and postoperative measurements were made, plasma VIP levels fell to the normal range with removal of the tumor and relief of the diarrhea; and (e) extracts of such tumors are rich in VIP-immunoreactivity and VIP-like biologic activity. A few patients with the syndrome have been reported to have normal plasma VIP levels, and it is possible that other humoral agents (such as pancreatic polypeptide, prostaglandins) may contribute to the production of the diarrhea.", "contents": "Vasoactive intestinal polypeptide (VIP) as a mediator of the watery diarrhea syndrome. Evidence that VIP is the principal humoral mediator of the watery diarrhea syndrome includes: (a) actions of VIP in experimental anaimals parallel the clinical manifestations of the syndrome; (b) infusions of VIP induce watery diarrhea in intestinal loops of dogs and a picture resembling the clinical syndrome in pigs, at circulating levels of the peptide similar to those observed in human disease; (c) most patients with the watery diarrhea syndrome and underlying tumors have elevated plasma levels of VIP; (d) in those patients in whom pre- and postoperative measurements were made, plasma VIP levels fell to the normal range with removal of the tumor and relief of the diarrhea; and (e) extracts of such tumors are rich in VIP-immunoreactivity and VIP-like biologic activity. A few patients with the syndrome have been reported to have normal plasma VIP levels, and it is possible that other humoral agents (such as pancreatic polypeptide, prostaglandins) may contribute to the production of the diarrhea."}
{"id": "PMID:229654", "title": "Heterotransplantation of human gastric carcinomas into nude mice.", "content": "A total of 33 specimens of human gastric carcinoma were used for transplantation into nude mice. Initital tumor \"take\" was accomplished in 15 of the 33 tumors, and the transplantability rate was 45.5%. Transplantability correlated with histologic type, but not with clinical stage or Borrmann's classification. The transplantability rate of differentiated carcinomas, such as well-differentiated tubular adenocarcinoma, moderately differentiated tubular adenocarcinoma, and papillary adenocarcinoma was greater than that of poorly differentiated tumors, such as poorly differentiated adenocarcinoma and mucinous adenocarcinoma. The growth patterns of transplanted tumors were divided into 3 types: rapid, slow, and persistent. There were no specific relationships between growth pattern and histologic type. All histologic types, except signet ring cell carcinoma, could be transplanted serially. Tumor growth became rapid after serial transfer. However, the original histology of these tumors was unchanged. No invasion or metastases were encountered. Intraperitoneal injection of a tumor cell suspension, prepared from subcutaneous transplants of a poorly differentiated adenocarcinoma of Borrmann type III, grew in an ascites form, with invasion and metastasis. Ascitic fluid accumulated within 3--6 weeks after injection. Subsequently, intravenous injection of ascites fluid produced metastases in nude mice. The histology of the subcutaneous tumor was similar to that of the original tumor from the patient.", "contents": "Heterotransplantation of human gastric carcinomas into nude mice. A total of 33 specimens of human gastric carcinoma were used for transplantation into nude mice. Initital tumor \"take\" was accomplished in 15 of the 33 tumors, and the transplantability rate was 45.5%. Transplantability correlated with histologic type, but not with clinical stage or Borrmann's classification. The transplantability rate of differentiated carcinomas, such as well-differentiated tubular adenocarcinoma, moderately differentiated tubular adenocarcinoma, and papillary adenocarcinoma was greater than that of poorly differentiated tumors, such as poorly differentiated adenocarcinoma and mucinous adenocarcinoma. The growth patterns of transplanted tumors were divided into 3 types: rapid, slow, and persistent. There were no specific relationships between growth pattern and histologic type. All histologic types, except signet ring cell carcinoma, could be transplanted serially. Tumor growth became rapid after serial transfer. However, the original histology of these tumors was unchanged. No invasion or metastases were encountered. Intraperitoneal injection of a tumor cell suspension, prepared from subcutaneous transplants of a poorly differentiated adenocarcinoma of Borrmann type III, grew in an ascites form, with invasion and metastasis. Ascitic fluid accumulated within 3--6 weeks after injection. Subsequently, intravenous injection of ascites fluid produced metastases in nude mice. The histology of the subcutaneous tumor was similar to that of the original tumor from the patient."}
{"id": "PMID:229657", "title": "Effects of dibutyryl cyclic AMP and cytochalasin B on cultured human glioma cells.", "content": "Cultured human glioma cells (138 MG) exposed to dibutyryl cyclic AMP (dbc-AMP; 0.1--5 mM) attained an arborized shape with thin processes extending from a rounded cell body. Cytochalasin B (CB; 1--1 muM) induced similar morphological changes. The processes in both dbc-AMP and CB treated cells were formed by retraction of the cell margin. Colchicine (1muM) completely and liver treated phalloidin (0.1 mg/ml) partially inhibited the morphological alterations induced by dbc-AMP and CB. Dbc-AMP was found to arrest cell movement, cell division and uptake of 2-deoxy-D-glucose. CB has the same effects but was more potent. The effects of dbc-AMP and CB could be due to interference with a common cellular structure, e.g. microfilaments.", "contents": "Effects of dibutyryl cyclic AMP and cytochalasin B on cultured human glioma cells. Cultured human glioma cells (138 MG) exposed to dibutyryl cyclic AMP (dbc-AMP; 0.1--5 mM) attained an arborized shape with thin processes extending from a rounded cell body. Cytochalasin B (CB; 1--1 muM) induced similar morphological changes. The processes in both dbc-AMP and CB treated cells were formed by retraction of the cell margin. Colchicine (1muM) completely and liver treated phalloidin (0.1 mg/ml) partially inhibited the morphological alterations induced by dbc-AMP and CB. Dbc-AMP was found to arrest cell movement, cell division and uptake of 2-deoxy-D-glucose. CB has the same effects but was more potent. The effects of dbc-AMP and CB could be due to interference with a common cellular structure, e.g. microfilaments."}
{"id": "PMID:229662", "title": "[Determination of total mercury in fish by means of a digestion method with HNO3/HClO3/HClO4 which does not lead to low results (author's transl)].", "content": "A digestion method for determination of total mercury in fish is described, which is economical, simple and reliable. Digestion is carried out by wet ashing with HNO3/HClO3/HClO4 in the presence of chloric acid. The procedure can be carried out at normal pressure in test tubes without suffering losses of Hg. The determination itself is carried out by the well known cold vapor atomic absorption method. This method was worked out specially for the regulatory control of fish, but can probably be used for related problems.", "contents": "[Determination of total mercury in fish by means of a digestion method with HNO3/HClO3/HClO4 which does not lead to low results (author's transl)]. A digestion method for determination of total mercury in fish is described, which is economical, simple and reliable. Digestion is carried out by wet ashing with HNO3/HClO3/HClO4 in the presence of chloric acid. The procedure can be carried out at normal pressure in test tubes without suffering losses of Hg. The determination itself is carried out by the well known cold vapor atomic absorption method. This method was worked out specially for the regulatory control of fish, but can probably be used for related problems."}
{"id": "PMID:229664", "title": "[Rotavirus diarrhea in young infants].", "content": "Clinical and serological studies were made in 62 children with various purulent infections, who were placed in the same hospital unit. The precipitation test with the antigen of monkey virus SA-11 showed that diarrhea in 32 of these children was etiologically linked with rotaviruses. The diagnostic titers of virus antibodies were detected in children having diarrhea 5.5 times as frequently as in the control group. The characteristic feature in the clinical picture of this diarrhea was the absence of the severe form.", "contents": "[Rotavirus diarrhea in young infants]. Clinical and serological studies were made in 62 children with various purulent infections, who were placed in the same hospital unit. The precipitation test with the antigen of monkey virus SA-11 showed that diarrhea in 32 of these children was etiologically linked with rotaviruses. The diagnostic titers of virus antibodies were detected in children having diarrhea 5.5 times as frequently as in the control group. The characteristic feature in the clinical picture of this diarrhea was the absence of the severe form."}
{"id": "PMID:229665", "title": "[Nervous system pathology in uterine myomas].", "content": "Clinico-physiological examinations of 218 patients with uterine myoma were carried out using the methods of electromyography and rheopgraphy. The following syndromes were revealed: a myopathic and a radiculoalgic ones; the syndrome of the external dermal femoral and the femorogenital nerves. The pathogenesis of these syndromes consists in compression of the lumbar arteries and the minor pelvis ganglia by the enlarged uterus. On condition of timely treatment including surgical ablation of the myoma the prognosis of the neurological disturbances is, as a rule, favourable.", "contents": "[Nervous system pathology in uterine myomas]. Clinico-physiological examinations of 218 patients with uterine myoma were carried out using the methods of electromyography and rheopgraphy. The following syndromes were revealed: a myopathic and a radiculoalgic ones; the syndrome of the external dermal femoral and the femorogenital nerves. The pathogenesis of these syndromes consists in compression of the lumbar arteries and the minor pelvis ganglia by the enlarged uterus. On condition of timely treatment including surgical ablation of the myoma the prognosis of the neurological disturbances is, as a rule, favourable."}
{"id": "PMID:229667", "title": "[Clinical and electromyographic characteristics of syndromes of pathologic muscular fatigue of the myasthenic type].", "content": "On the basis of the follow-up study of more than 2000 patients with different forms of pathological muscular fatiguability of the myasthenic type, the authors emphasize the heterogeneity of this group of patients. The detailed study of clinical and electromyographic picture permitted them to distinguish the following clinical forms; myasthenia, myasthenic syndrome in terminal polyneuropathy, the myastheniapolymyositis complex, myasthenic syndrome of Lambert--Etone type.", "contents": "[Clinical and electromyographic characteristics of syndromes of pathologic muscular fatigue of the myasthenic type]. On the basis of the follow-up study of more than 2000 patients with different forms of pathological muscular fatiguability of the myasthenic type, the authors emphasize the heterogeneity of this group of patients. The detailed study of clinical and electromyographic picture permitted them to distinguish the following clinical forms; myasthenia, myasthenic syndrome in terminal polyneuropathy, the myastheniapolymyositis complex, myasthenic syndrome of Lambert--Etone type."}
{"id": "PMID:229670", "title": "Na,K-ATPase in excitation-contraction coupling of vascular smooth muscle from cattle.", "content": "Lowering the extracellular K+ content from 6 to 0.6 mM causes a rise, and elevation from 6 to 8.5 mM a fall of 45Ca++ efflux from the vascular smooth muscle cells of the arteria carotis communis of cattle. In contrast, a level of 17 mM K+ has no influence. Removal of extracellular calcium does not block these effects. 10(-4) M ouabain also induces a rise in Ca++ efflux, additional potassium reduction then being without effect; 10(-9) M ouabain is of no influence. The 45Ca++ efflux kinetics correlates with the activity of the isolated Na,K-ATPase. Tonus increases of the vascular strips by 10(-4) M ouabain and potassium deficiency cannot be blocked by 4 mM lanthanum or removal of extracellular calcium. Unlike sodium, potassium stimulates the active Ca++ binding and the activity of the Ca-ATPase of the microsomal fraction. The ative Ca++ binding of the mitochondria is stimulated by both ions. It is postulated that the activity of the plasma membrane Na,K-pump is able to regulate the tonus of big arteries through alteration of Ca++ storage processes.", "contents": "Na,K-ATPase in excitation-contraction coupling of vascular smooth muscle from cattle. Lowering the extracellular K+ content from 6 to 0.6 mM causes a rise, and elevation from 6 to 8.5 mM a fall of 45Ca++ efflux from the vascular smooth muscle cells of the arteria carotis communis of cattle. In contrast, a level of 17 mM K+ has no influence. Removal of extracellular calcium does not block these effects. 10(-4) M ouabain also induces a rise in Ca++ efflux, additional potassium reduction then being without effect; 10(-9) M ouabain is of no influence. The 45Ca++ efflux kinetics correlates with the activity of the isolated Na,K-ATPase. Tonus increases of the vascular strips by 10(-4) M ouabain and potassium deficiency cannot be blocked by 4 mM lanthanum or removal of extracellular calcium. Unlike sodium, potassium stimulates the active Ca++ binding and the activity of the Ca-ATPase of the microsomal fraction. The ative Ca++ binding of the mitochondria is stimulated by both ions. It is postulated that the activity of the plasma membrane Na,K-pump is able to regulate the tonus of big arteries through alteration of Ca++ storage processes."}
{"id": "PMID:229671", "title": "A thermodynamic-kinetic analysis of the cytochrome P-450 heme pocket.", "content": "Spin state changes in the iron center of cytochrome P-450 during the catalytic cycle suggest alterations in the heme environment that insure proper substrate binding, an increase in redox potential, the formation of an active Fe-O complex, and the attack on the substrate. We used the spin state changes of the iron following physico-chemical perturbations, as an intrinsic probe of discrete changes around the heme, or of larger ones in the protein conformation. These environmental perturbations included temperature, solvent, substrate, and ionic environment. Aqueous and hydro-organic buffers provide complementary data and interpretations; the mixed solvent accommodates temperatures suitable for direct reaction rate measurements and amplified low to high spin transition. The results suggest that the group determining the heme spin state is influenced by the electrostatic potential created by several negative charges near the heme; the modulation of the spin state by various factors reflects the modulation of the electrostatic potential and of the internal paH value. Conformational changes of the whole protein are also indicated by the large entropy terms and their variation with experimental conditions.", "contents": "A thermodynamic-kinetic analysis of the cytochrome P-450 heme pocket. Spin state changes in the iron center of cytochrome P-450 during the catalytic cycle suggest alterations in the heme environment that insure proper substrate binding, an increase in redox potential, the formation of an active Fe-O complex, and the attack on the substrate. We used the spin state changes of the iron following physico-chemical perturbations, as an intrinsic probe of discrete changes around the heme, or of larger ones in the protein conformation. These environmental perturbations included temperature, solvent, substrate, and ionic environment. Aqueous and hydro-organic buffers provide complementary data and interpretations; the mixed solvent accommodates temperatures suitable for direct reaction rate measurements and amplified low to high spin transition. The results suggest that the group determining the heme spin state is influenced by the electrostatic potential created by several negative charges near the heme; the modulation of the spin state by various factors reflects the modulation of the electrostatic potential and of the internal paH value. Conformational changes of the whole protein are also indicated by the large entropy terms and their variation with experimental conditions."}
{"id": "PMID:229668", "title": "[Pyramidal approaches to surgical treatment of pathologic formations of the cerebellopontine angle and pyramids of the temporal bone].", "content": "Pyramidal approaches are sufficiently effective, cause little traumas, and are easily tolerated by the patients. They are indicated in surgical management of diseases of the cerebellopontine angle such as tumors (neurinoma of the auditory nerve, cholesteatoma), cystic arachnoiditis, tumors of the temporal bone pyramid (glomus tumors, cysts), compression of the facial nerve in mechanical trauma of the pyramid, etc. The choice of the variant of the pyramidal approach to the pathological focus should be guided by the following main criteria: localization of the process and the extent of its spreading; condition of the facial nerve; condition of the auditory function.", "contents": "[Pyramidal approaches to surgical treatment of pathologic formations of the cerebellopontine angle and pyramids of the temporal bone]. Pyramidal approaches are sufficiently effective, cause little traumas, and are easily tolerated by the patients. They are indicated in surgical management of diseases of the cerebellopontine angle such as tumors (neurinoma of the auditory nerve, cholesteatoma), cystic arachnoiditis, tumors of the temporal bone pyramid (glomus tumors, cysts), compression of the facial nerve in mechanical trauma of the pyramid, etc. The choice of the variant of the pyramidal approach to the pathological focus should be guided by the following main criteria: localization of the process and the extent of its spreading; condition of the facial nerve; condition of the auditory function."}
{"id": "PMID:229672", "title": "Cytochrome P-450cam and putidaredoxin interaction during electron transfer.", "content": "Cytochrome P-450cam, the bacterial hemeprotein which catalyzes the 5-exo-hydroxylation of d-camphor, requires two electrons to activate molecular oxygen for this monooxygenase reaction. These two electrons are transferred to cytochrome P-450cam in two one-electron steps by the physiological reductant, putidaredoxin. The present study of the kinetics of reduction of cytochrome P-450cam by reduced putidaredoxin has shown that the reaction obeys first order kinetics with a rate constant of 33 s-1 at 25 degrees C with respect to: 1) the appearance of the carbon monoxide complex of Fe(II) cytochrome P-450cam; 2) the disappearance of the 645 nm absorbance band of high-spin Fe(III) cytochrome P-450cam; and 3) the disappearance of the g = 1.94 EPR signal of reduced putidaredoxin. This data was interpreted as indicative of the rapid formation of a bimolecular complex between reduced putidaredoxin Fe(III) cytochrome P-450cam. The existence of the complex was first shown indirectly by kinetic analysis and secondly directly by electron paramagnetic resonance spectroscopic analysis of samples which were freeze-quenched approximately 16 ms after mixing. The direct evidence for complex formation was the loss of the EPR signal of Fe(III) cytochrome P-450cam upon formation of the complex while the EPR signal of reduced putidaredoxin decays with the same kinetics as the appearance of Fe(II) cytochrome P-450. The mechanism of the loss of the EPR signal of cytochrome P-450 upon formation of the complex is not apparent at this time but may involve a conformational change of cytochrome P-450cam following complex formation.", "contents": "Cytochrome P-450cam and putidaredoxin interaction during electron transfer. Cytochrome P-450cam, the bacterial hemeprotein which catalyzes the 5-exo-hydroxylation of d-camphor, requires two electrons to activate molecular oxygen for this monooxygenase reaction. These two electrons are transferred to cytochrome P-450cam in two one-electron steps by the physiological reductant, putidaredoxin. The present study of the kinetics of reduction of cytochrome P-450cam by reduced putidaredoxin has shown that the reaction obeys first order kinetics with a rate constant of 33 s-1 at 25 degrees C with respect to: 1) the appearance of the carbon monoxide complex of Fe(II) cytochrome P-450cam; 2) the disappearance of the 645 nm absorbance band of high-spin Fe(III) cytochrome P-450cam; and 3) the disappearance of the g = 1.94 EPR signal of reduced putidaredoxin. This data was interpreted as indicative of the rapid formation of a bimolecular complex between reduced putidaredoxin Fe(III) cytochrome P-450cam. The existence of the complex was first shown indirectly by kinetic analysis and secondly directly by electron paramagnetic resonance spectroscopic analysis of samples which were freeze-quenched approximately 16 ms after mixing. The direct evidence for complex formation was the loss of the EPR signal of Fe(III) cytochrome P-450cam upon formation of the complex while the EPR signal of reduced putidaredoxin decays with the same kinetics as the appearance of Fe(II) cytochrome P-450. The mechanism of the loss of the EPR signal of cytochrome P-450 upon formation of the complex is not apparent at this time but may involve a conformational change of cytochrome P-450cam following complex formation."}
{"id": "PMID:229673", "title": "Spin state transitions of liver microsomal cytochrome P-450.", "content": "Spin state transitions of membrane-bound cytochrome P-450 were investigated by difference spectrophotometry using the 'D'-charge transfer absorbance band at 645 nm as a measure of the amount of hemin iron present in the 5-coordinated state. The magnitude of the 'D'-absorbance band in the absence of exogenous substrates, e.g., the concentration of native high spin cytochrome P-450, was evaluated from the difference in absorbance at 645 nm between ferric cytochrome P-450 and the carbon monoxide derivative of the pigment in its ferrous state. The contribution of the native high spin species to the total cytochrome P-450 content of microsomes was calculated to be between 40% and 65% after induction with phenobarbital and polycyclic hydrocarbons, respectively. Up to 80% of the cytochrome P-450 was found to be present in the high spin state after the addition of exogenous substrates. Further, the steady state concentrations of high spin cytochrome P-450, observed in the presence of reduced pyridine nucleotides, suggest that the rate limiting step for microsomal mixed function oxidation reactions is variable and dependent on the substrate under investigation.", "contents": "Spin state transitions of liver microsomal cytochrome P-450. Spin state transitions of membrane-bound cytochrome P-450 were investigated by difference spectrophotometry using the 'D'-charge transfer absorbance band at 645 nm as a measure of the amount of hemin iron present in the 5-coordinated state. The magnitude of the 'D'-absorbance band in the absence of exogenous substrates, e.g., the concentration of native high spin cytochrome P-450, was evaluated from the difference in absorbance at 645 nm between ferric cytochrome P-450 and the carbon monoxide derivative of the pigment in its ferrous state. The contribution of the native high spin species to the total cytochrome P-450 content of microsomes was calculated to be between 40% and 65% after induction with phenobarbital and polycyclic hydrocarbons, respectively. Up to 80% of the cytochrome P-450 was found to be present in the high spin state after the addition of exogenous substrates. Further, the steady state concentrations of high spin cytochrome P-450, observed in the presence of reduced pyridine nucleotides, suggest that the rate limiting step for microsomal mixed function oxidation reactions is variable and dependent on the substrate under investigation."}
{"id": "PMID:229674", "title": "Quantitative analysis of the spin equilibrium of cytochrome P-450 LM2 fraction from rabbit liver microsomes.", "content": "The LM2 fraction of cytochrome P-450 from phenobarbital induced rabbit liver microsomes in the presence and in the absence of substrate (benzphetamine) is shown to be a thermal equilibrium of a high spin (S = 5/2) and a low spin (S = 1/2) state each of which exhibiting its individual optical basic spectrum with the Soret maxima at 387 nm and 417 nm for the high spin form and the low spin form, respectively. The equilibrium constants and thermodynamic parameters describing the spin transition and the substrate binding have been evaluated from the temperature and substrate difference spectra. These two interacting equilibria are presented in terms of a thermodynamic model, which provides a quantitative description of the relationship between the substrate binding and the spin equilibrium. From kinetic experiments it is concluded that the spin equilibrium is an electronic one and is not caused by iron ligand dissociation.", "contents": "Quantitative analysis of the spin equilibrium of cytochrome P-450 LM2 fraction from rabbit liver microsomes. The LM2 fraction of cytochrome P-450 from phenobarbital induced rabbit liver microsomes in the presence and in the absence of substrate (benzphetamine) is shown to be a thermal equilibrium of a high spin (S = 5/2) and a low spin (S = 1/2) state each of which exhibiting its individual optical basic spectrum with the Soret maxima at 387 nm and 417 nm for the high spin form and the low spin form, respectively. The equilibrium constants and thermodynamic parameters describing the spin transition and the substrate binding have been evaluated from the temperature and substrate difference spectra. These two interacting equilibria are presented in terms of a thermodynamic model, which provides a quantitative description of the relationship between the substrate binding and the spin equilibrium. From kinetic experiments it is concluded that the spin equilibrium is an electronic one and is not caused by iron ligand dissociation."}
{"id": "PMID:229675", "title": "The importance of the spin equilibrium in cytochrome P-450 for the reduction rate of the heme iron.", "content": "Based on the existence of a spin equilibrium of P-450 LM a thermodynamic model including the first two elementary steps has been developed. This model has been compared with a modified model of P-450 CAM first presented by SLIGAR [1]. For the quantitative description of the model of P-450 LM seven necessary constants have been calculated. In the model a 5-coordinated ferric heme complex as intermediate and precursor of the reduced state is included. The model is based on experimental data of the spin equilibrium and the binding of benzphetamine to P-450 LM2, on the redox potential of P-450 LM and further on the assumption of a structure of the precursor well adapted to reduction. The dissociation constant (KD) of the 6th heme iron ligand is calculated to be 0.03 meaning that only 3% of the high spin ferric state are 5-coordinated. From the thermodynamic parameters of the model the sequential order of the reaction process can be derived and conclusions can be drawn on possibly reaction controlling steps. Experimentally it is shown that the substrate induced spin shift is correlated with the reduction rate. This has been shown to be valid in dependence on the degree of saturation with only one substrate as well as with different substrates indicating that independent of the individual substrate only the shift of the spin state controls the reduction. From the experiments as well as from the model it can be concluded that P-450 works in the first reaction step in two states (different in structural and functional properties) being in equilibrium with each other. Different affinities of these two states towards the substrate shift the equilibrium. This shift increases the concentration of the reducible intermediate and by this the reduction as second elementary step is regulated.", "contents": "The importance of the spin equilibrium in cytochrome P-450 for the reduction rate of the heme iron. Based on the existence of a spin equilibrium of P-450 LM a thermodynamic model including the first two elementary steps has been developed. This model has been compared with a modified model of P-450 CAM first presented by SLIGAR [1]. For the quantitative description of the model of P-450 LM seven necessary constants have been calculated. In the model a 5-coordinated ferric heme complex as intermediate and precursor of the reduced state is included. The model is based on experimental data of the spin equilibrium and the binding of benzphetamine to P-450 LM2, on the redox potential of P-450 LM and further on the assumption of a structure of the precursor well adapted to reduction. The dissociation constant (KD) of the 6th heme iron ligand is calculated to be 0.03 meaning that only 3% of the high spin ferric state are 5-coordinated. From the thermodynamic parameters of the model the sequential order of the reaction process can be derived and conclusions can be drawn on possibly reaction controlling steps. Experimentally it is shown that the substrate induced spin shift is correlated with the reduction rate. This has been shown to be valid in dependence on the degree of saturation with only one substrate as well as with different substrates indicating that independent of the individual substrate only the shift of the spin state controls the reduction. From the experiments as well as from the model it can be concluded that P-450 works in the first reaction step in two states (different in structural and functional properties) being in equilibrium with each other. Different affinities of these two states towards the substrate shift the equilibrium. This shift increases the concentration of the reducible intermediate and by this the reduction as second elementary step is regulated."}
{"id": "PMID:229676", "title": "Activated forms of oxygen in the metabolism of xenobiotics catalyzed by cytochrome P-450.", "content": "The Cu(Lys)2 complex is shown to be an effective inhibitor of the oxidation of 3,4-benzpyrene and aniline in microsomes. Apparently, this is due to the dismutation of superoxide radicals involved in the metabolism of these compounds. Possible interactions between Cu(Lys)2 and model membranes have been studied using spin probes. A model has been suggested according to which Cu(Lys)2 \"builds\" in the membrane hydrocarbon regions.", "contents": "Activated forms of oxygen in the metabolism of xenobiotics catalyzed by cytochrome P-450. The Cu(Lys)2 complex is shown to be an effective inhibitor of the oxidation of 3,4-benzpyrene and aniline in microsomes. Apparently, this is due to the dismutation of superoxide radicals involved in the metabolism of these compounds. Possible interactions between Cu(Lys)2 and model membranes have been studied using spin probes. A model has been suggested according to which Cu(Lys)2 \"builds\" in the membrane hydrocarbon regions."}
{"id": "PMID:229677", "title": "Comparison of spectral properties of 3-MC induced cytochrome P-448 from rabbits and rats.", "content": "EPR and optical spectral properties of cytochrome P-488 from 3-methylcholanthrene-induced rabbits are compared with those of rats. In the EPR spectra at 77K and in the optical absorption spectra at room temperature a considerable temperature independent high spin content of the rabbit cytochrome is observed which has been estimated to about 55% by titration with n-octylamine. On the other hand the high spin content of the rat cytochrome depends strongly on temperature and amounts to about 6% at 5 degrees C and to about 35% at 34 degrees C. The binding of substrates and ligands to the rabbit cytochrome as well as its reduction by sodium dithionite are slower as compared with the rat cytochrome but also with phenobarbital-induced cytochrome P-450 from rats and rabbits. Contrary to the 3-methylcholanthrene induced cytochrome P-448 from rats, that from rabbits does not bind 3-methylcholanthrene. A particular protein structure establishing the high spin state and an absent binding site for type I substrates is assumed to be responsible for these and other peculiarities of cytochrome P-448 from 3-methylcholanthrene-induced rabbits.", "contents": "Comparison of spectral properties of 3-MC induced cytochrome P-448 from rabbits and rats. EPR and optical spectral properties of cytochrome P-488 from 3-methylcholanthrene-induced rabbits are compared with those of rats. In the EPR spectra at 77K and in the optical absorption spectra at room temperature a considerable temperature independent high spin content of the rabbit cytochrome is observed which has been estimated to about 55% by titration with n-octylamine. On the other hand the high spin content of the rat cytochrome depends strongly on temperature and amounts to about 6% at 5 degrees C and to about 35% at 34 degrees C. The binding of substrates and ligands to the rabbit cytochrome as well as its reduction by sodium dithionite are slower as compared with the rat cytochrome but also with phenobarbital-induced cytochrome P-450 from rats and rabbits. Contrary to the 3-methylcholanthrene induced cytochrome P-448 from rats, that from rabbits does not bind 3-methylcholanthrene. A particular protein structure establishing the high spin state and an absent binding site for type I substrates is assumed to be responsible for these and other peculiarities of cytochrome P-448 from 3-methylcholanthrene-induced rabbits."}
{"id": "PMID:229678", "title": "Comparison of microsomal and solubilized monooxygenases from rat and rabbit by proton magnetic relaxation.", "content": "The paper presents results of a comparative study of the haem environment, by proton magnetic relaxation, in P-450 and P-448 monooxygenases from rat and rabbit, induced by phenobarbital and 3-methylcholanthrene, in both species. It was established that the method yields information on the accessibility of the haem iron for solvent molecules (protons), both in microsomes and in solubilized samples of various degrees of purification, i.e. association. The state of micelles in the solutions does not alter the haem iron accessibility. A slight difference was found for the microsomes suspended in a phosphate vs. pyrophosphate buffer, but this is without any consequence with regard to the species and form differences. The correlation time for the highly purified LM2 fraction of rabbit P-450 could not be determined more precisely than before for a sample of lower purity, because the relaxation rates are frequency independent. The correlation time for the rat P-448 monooxygenase was determined by dispersion measurements to be (4.1 +/- 0.4) x 10(-11) s. It was found that the PMRx behaviours of rabbit and rat monooxygenases are more alike in microsomes than in the partially purified solubilized form. The solubilization produces a pronounced alteration of the PMRx temperature dependence only for the rat 3-MC induced monooxygenase P-448. For the P-450 form the haem iron becomes less accessible on solubilization, both for the rabbit and the rat liver monooxygenases, whereas in case of rat liver P-448 the accessibility is considerably enhanced on solubilization. There is a substantial structural specificity of the haem environments from the two animal species, the one from rat being tighter. The reduced, NO-bound rabbit liver monooxygenase was studied also, but the results are not yet conclusive, except the fact that the unpaired spin from NO is thoroughly shielded from the solvent compared with the haem iron from the original sample. The following series of increased haem-iron accessibility emerges from the PMRx studies known so far: rat (P-448) less than rabbit (P-448) less than rat (P-450) less than rabbit (P-450) in microsomes, and rabbit (P-448, with 3-MC bound?) less than Pseudomonas putida (P-450) rat less than (P-448), less than rat (P-450) less than rabbit (P-450) from solubilized samples. For the latter, it appears that increased enzymic specificity goes along with a closing of the haem cleft.", "contents": "Comparison of microsomal and solubilized monooxygenases from rat and rabbit by proton magnetic relaxation. The paper presents results of a comparative study of the haem environment, by proton magnetic relaxation, in P-450 and P-448 monooxygenases from rat and rabbit, induced by phenobarbital and 3-methylcholanthrene, in both species. It was established that the method yields information on the accessibility of the haem iron for solvent molecules (protons), both in microsomes and in solubilized samples of various degrees of purification, i.e. association. The state of micelles in the solutions does not alter the haem iron accessibility. A slight difference was found for the microsomes suspended in a phosphate vs. pyrophosphate buffer, but this is without any consequence with regard to the species and form differences. The correlation time for the highly purified LM2 fraction of rabbit P-450 could not be determined more precisely than before for a sample of lower purity, because the relaxation rates are frequency independent. The correlation time for the rat P-448 monooxygenase was determined by dispersion measurements to be (4.1 +/- 0.4) x 10(-11) s. It was found that the PMRx behaviours of rabbit and rat monooxygenases are more alike in microsomes than in the partially purified solubilized form. The solubilization produces a pronounced alteration of the PMRx temperature dependence only for the rat 3-MC induced monooxygenase P-448. For the P-450 form the haem iron becomes less accessible on solubilization, both for the rabbit and the rat liver monooxygenases, whereas in case of rat liver P-448 the accessibility is considerably enhanced on solubilization. There is a substantial structural specificity of the haem environments from the two animal species, the one from rat being tighter. The reduced, NO-bound rabbit liver monooxygenase was studied also, but the results are not yet conclusive, except the fact that the unpaired spin from NO is thoroughly shielded from the solvent compared with the haem iron from the original sample. The following series of increased haem-iron accessibility emerges from the PMRx studies known so far: rat (P-448) less than rabbit (P-448) less than rat (P-450) less than rabbit (P-450) in microsomes, and rabbit (P-448, with 3-MC bound?) less than Pseudomonas putida (P-450) rat less than (P-448), less than rat (P-450) less than rabbit (P-450) from solubilized samples. For the latter, it appears that increased enzymic specificity goes along with a closing of the haem cleft."}
{"id": "PMID:229679", "title": "Stereochemical properties of the binding site of liver microsomal cytochrome P-450 as studied by substrate analogous spin labels.", "content": "For the characterization of the substrate binding site optical and EPR measurements with spin labelled substrates on solubilized and pure cytochrome P-450 were performed. Analogously to the unlabelled derivatives spin labelled n-alkylamines and isocyanides with different chain lengths are type II substrates. The Ks-values evaluated from optical (P-450 = 1.98 . 10(-6) M) and ESR (P-450 = 1.98 . 10(-4) M) measurements are very similar indicating no concentration dependences. Contrary to the unlabelled n-alkylamines the spin labelled compounds show an affinity almost independent of the chain lengths. The SL-substrates with a short distance between the functional group and the NO-group bound to P-450 induce pronounced changes of the ligand field of the heme iron and a large broadening of the signal of the immobilized nitroxide indicating intensive interactions between the unpaired electron of the nitroxide group and the paramagnetic heme iron. Elongation of the alkyl chains results in spectra of the Fe3+ complexes with only slight modification and a remained unbroadened signal of the immobilized nitroxide. The binding of the substrate through their functional groups together with a 1:1 stoichiometry of the P-450 SL-IC-complex give evidence for the same binding site in the near vicinity of the heme iron.", "contents": "Stereochemical properties of the binding site of liver microsomal cytochrome P-450 as studied by substrate analogous spin labels. For the characterization of the substrate binding site optical and EPR measurements with spin labelled substrates on solubilized and pure cytochrome P-450 were performed. Analogously to the unlabelled derivatives spin labelled n-alkylamines and isocyanides with different chain lengths are type II substrates. The Ks-values evaluated from optical (P-450 = 1.98 . 10(-6) M) and ESR (P-450 = 1.98 . 10(-4) M) measurements are very similar indicating no concentration dependences. Contrary to the unlabelled n-alkylamines the spin labelled compounds show an affinity almost independent of the chain lengths. The SL-substrates with a short distance between the functional group and the NO-group bound to P-450 induce pronounced changes of the ligand field of the heme iron and a large broadening of the signal of the immobilized nitroxide indicating intensive interactions between the unpaired electron of the nitroxide group and the paramagnetic heme iron. Elongation of the alkyl chains results in spectra of the Fe3+ complexes with only slight modification and a remained unbroadened signal of the immobilized nitroxide. The binding of the substrate through their functional groups together with a 1:1 stoichiometry of the P-450 SL-IC-complex give evidence for the same binding site in the near vicinity of the heme iron."}
{"id": "PMID:229680", "title": "Model systems for the coordination chemistry of cytochrome P-450.", "content": "Studies on model complexes have supported the presence of a mercaptide as the fifth ligand of cytochrome P-450 monooxygenases. When alcohol or thiol ligands are added to the sixth coordination position of a five-coordinated 4-nitrobenzene thiolate complex of FeIII protoporphyrin IX dimethyl ester chloride low spin complexes with optical and EPR-spectra very similar to cytochrome P-450 are obtained. From a comparison with all ligands of cytochrome P-450 and the model complexes it is concluded that a hard ligands must occupy the sixth coordination position of cytochrome P-450. An imidazole group is less likely, also in view of the ligand field parameters. The significance of the fifth and sixth ligand of cytochrome P-450 is discussed with respect to the monooxygenase mechanism.", "contents": "Model systems for the coordination chemistry of cytochrome P-450. Studies on model complexes have supported the presence of a mercaptide as the fifth ligand of cytochrome P-450 monooxygenases. When alcohol or thiol ligands are added to the sixth coordination position of a five-coordinated 4-nitrobenzene thiolate complex of FeIII protoporphyrin IX dimethyl ester chloride low spin complexes with optical and EPR-spectra very similar to cytochrome P-450 are obtained. From a comparison with all ligands of cytochrome P-450 and the model complexes it is concluded that a hard ligands must occupy the sixth coordination position of cytochrome P-450. An imidazole group is less likely, also in view of the ligand field parameters. The significance of the fifth and sixth ligand of cytochrome P-450 is discussed with respect to the monooxygenase mechanism."}
{"id": "PMID:229681", "title": "Isolation and characterization of cytochrome P-450meg.", "content": "The cytochrome P-450-dependent steroid 15 beta-hydroxylase system from Bacillus megaterium has been resolved into three components, 1) a NADPH-specific, FMN-containing flavoprotein reductase, molecular weight 55-60 000; 2) an iron-sulfur protein, molecular weight 13,000 and 3) cytochrome P-450meg, molecular weight 52,000. The cytochrome component has been purified to homogeneity, as judged by SDS-polyacrylamide gel electrophoresis and isoelectric focusing in polyacrylamide gel, and its amino acid composition has been determined. Cytochrome P-450meg has a pI of 4.9, a Stokes radius of 27 A and a sedimentation constant of 3.3 S. Electron paramagnetic resonance and optical spectra are typical of a low-spin cytochrome P-450. The fluorescence spectrum is indicative of a tryptophane residue in a relatively non-polar environment. In recombination experiments, the electron flow was shown to proceed from the reductase via the iron-sulfur protein to the cytochrome. It is also possible to exchange the different components of the mitochondrial 11 beta-hydroxylase system from bovine adrenals for corresponding components in B. megaterium. Substrate specificity studies indicate that only steroids with a 3-oxo-delta 4-configuration are hydroxylated by the B. megaterium hydroxylase system. When oxidizing agents were used, hydroxylation occurred both in positions 15 alpha and 15 beta. Further substrate specificity studies have shown that aniline and imipramine can function as substrates for the bacterial system.", "contents": "Isolation and characterization of cytochrome P-450meg. The cytochrome P-450-dependent steroid 15 beta-hydroxylase system from Bacillus megaterium has been resolved into three components, 1) a NADPH-specific, FMN-containing flavoprotein reductase, molecular weight 55-60 000; 2) an iron-sulfur protein, molecular weight 13,000 and 3) cytochrome P-450meg, molecular weight 52,000. The cytochrome component has been purified to homogeneity, as judged by SDS-polyacrylamide gel electrophoresis and isoelectric focusing in polyacrylamide gel, and its amino acid composition has been determined. Cytochrome P-450meg has a pI of 4.9, a Stokes radius of 27 A and a sedimentation constant of 3.3 S. Electron paramagnetic resonance and optical spectra are typical of a low-spin cytochrome P-450. The fluorescence spectrum is indicative of a tryptophane residue in a relatively non-polar environment. In recombination experiments, the electron flow was shown to proceed from the reductase via the iron-sulfur protein to the cytochrome. It is also possible to exchange the different components of the mitochondrial 11 beta-hydroxylase system from bovine adrenals for corresponding components in B. megaterium. Substrate specificity studies indicate that only steroids with a 3-oxo-delta 4-configuration are hydroxylated by the B. megaterium hydroxylase system. When oxidizing agents were used, hydroxylation occurred both in positions 15 alpha and 15 beta. Further substrate specificity studies have shown that aniline and imipramine can function as substrates for the bacterial system."}
{"id": "PMID:229682", "title": "Oxycytochrome P-450: its breakdown to superoxide for the formation of hydrogen peroxide.", "content": "Four different experimental studies are described which were designed to evaluate the role of oxycytochrome P-450 in the formation of superoxide anions and hydrogen peroxide. The use of lipophilic copper chelates with superoxide dismutase like activity revealed that the primary site of interaction of these agents is related to the inhibition of the flavoprotein. NADPH-cytochrome P-450 reductase. Measurements of the proton assisted nucleophilic displacement of superoxide from oxycytochrome P-450 by high concentrations of sodium azide indicated an increase in the rate of hydrogen peroxide formation concomitant with the inhibition of the N-demethylation of ethylmorphine. Studies on the effect of NADH on the rate of hydrogen peroxide formation during NADPH oxidation by liver microsomes failed to reveal a stimulatory or synergistic effect in a manner analogous to results obtained during the cytochrome P-450 dependent oxidation of substrates such as ethylmorphine. These results suggest that hydrogen peroxide formation may not require the reduction of oxycytochrome P-450 to peroxycytochrome P-450. Measurements of the reduction of succinylated cytochrome c using purified cytochrome P-450 and the flavoprotein, NADPH-cytochrome P-450 reductase, directly demonstrate the formation of superoxide anions. It is concluded that oxycytochrome P-450 may decompose to generate hydrogen peroxide.", "contents": "Oxycytochrome P-450: its breakdown to superoxide for the formation of hydrogen peroxide. Four different experimental studies are described which were designed to evaluate the role of oxycytochrome P-450 in the formation of superoxide anions and hydrogen peroxide. The use of lipophilic copper chelates with superoxide dismutase like activity revealed that the primary site of interaction of these agents is related to the inhibition of the flavoprotein. NADPH-cytochrome P-450 reductase. Measurements of the proton assisted nucleophilic displacement of superoxide from oxycytochrome P-450 by high concentrations of sodium azide indicated an increase in the rate of hydrogen peroxide formation concomitant with the inhibition of the N-demethylation of ethylmorphine. Studies on the effect of NADH on the rate of hydrogen peroxide formation during NADPH oxidation by liver microsomes failed to reveal a stimulatory or synergistic effect in a manner analogous to results obtained during the cytochrome P-450 dependent oxidation of substrates such as ethylmorphine. These results suggest that hydrogen peroxide formation may not require the reduction of oxycytochrome P-450 to peroxycytochrome P-450. Measurements of the reduction of succinylated cytochrome c using purified cytochrome P-450 and the flavoprotein, NADPH-cytochrome P-450 reductase, directly demonstrate the formation of superoxide anions. It is concluded that oxycytochrome P-450 may decompose to generate hydrogen peroxide."}
{"id": "PMID:229683", "title": "Comparison of the peroxidatic activity of cytochrome P-450 with other hemoproteins and model compounds.", "content": "The H2O2 dependent catalysis of cytochrome P-450 was compared with the catalytic mechanism of horse radish peroxidase, methemoglobin and iron protoporphyrin complexes. A relatively stable intermediate being comparable to compound I of horse radish peroxidase is formed in the case of iron porphyrin complexes, methemoglobin and probably cytochrome P-450. In the case of peroxidase compound II is the more stable intermediate. This could be the reason for the different catalytic properties of peroxidase on the one hand and iron porphyrin complexes, methemoglobin and cytochrome P-450 on the other hand.", "contents": "Comparison of the peroxidatic activity of cytochrome P-450 with other hemoproteins and model compounds. The H2O2 dependent catalysis of cytochrome P-450 was compared with the catalytic mechanism of horse radish peroxidase, methemoglobin and iron protoporphyrin complexes. A relatively stable intermediate being comparable to compound I of horse radish peroxidase is formed in the case of iron porphyrin complexes, methemoglobin and probably cytochrome P-450. In the case of peroxidase compound II is the more stable intermediate. This could be the reason for the different catalytic properties of peroxidase on the one hand and iron porphyrin complexes, methemoglobin and cytochrome P-450 on the other hand."}
{"id": "PMID:229685", "title": "Serum levels of somatomedin A and growth during long-term treatment of patients with pituitary dwarfism with human growth hormone.", "content": "Eighteen patients with pituitary dwarfism were treated for 1 7/12 to 6 years with human growth hormone (hGH) at a dose of 0.19--0.62 unit (U) per kg of body weight per week. The mean increment in height was 2.0 +/- 0.4 and 8.8 +/- 0.5 cm/year before and the first year after treatment of hGH, respectively. A significant positive correlation was observed between serum levels of somatomedin A and growth rate, espcially in children with bone age below 10 and a duration of treatment of less than one year (r = 0.66, P less than 0.005). Long-term treatment with hGH was accompanied by a decreasing response. However, the serum levels of somatomedin A did not decrease significantly. Therefore, decreased growth increment in these situations was not due to decreased serum levels of somatomedin A.", "contents": "Serum levels of somatomedin A and growth during long-term treatment of patients with pituitary dwarfism with human growth hormone. Eighteen patients with pituitary dwarfism were treated for 1 7/12 to 6 years with human growth hormone (hGH) at a dose of 0.19--0.62 unit (U) per kg of body weight per week. The mean increment in height was 2.0 +/- 0.4 and 8.8 +/- 0.5 cm/year before and the first year after treatment of hGH, respectively. A significant positive correlation was observed between serum levels of somatomedin A and growth rate, espcially in children with bone age below 10 and a duration of treatment of less than one year (r = 0.66, P less than 0.005). Long-term treatment with hGH was accompanied by a decreasing response. However, the serum levels of somatomedin A did not decrease significantly. Therefore, decreased growth increment in these situations was not due to decreased serum levels of somatomedin A."}
{"id": "PMID:229687", "title": "Sex difference in the induction of lactogenic receptors in rat livers.", "content": "The relationship between serum levels of growth hormone (rGH), prolactin (rPRL), luteinizing hormone (rLH), follicle-stimulating hormone (rFSH), corticosterone, oestrogen, (oestradiol-17 beta) and testosterone and the hepatic binding sites specific to [125I]human-prolactin (h-PRL) were investigated in normal rats, in rats bearing the GH- and PRL-secreting tumour (GH3), and in rats 14 days after tumour removal. The presence of GH3 tumour elevated serum levels of rGH and rPRL and concomitantly increased the hepatic binding of [125I]h-PRL; the male rats had a greater increase than the female rats. The increased binding was due to an increase in the specific membrane binding sites, whereas the affinity constant (Ka) was not changed. In both male and female rats, there was a significant positive correlation between ser-m rGH levels (P less than 0.001) or serum rPRL (P less than 0.02) and specific binding of [125I]h-PRL in female rats only (P less than 0.02). In male rats, there was a significant negative correlation between serum testosterone levels and specific bindings of [125I]h-PRL (P less than 0.05). These results suggest that rGH and rPRL regulates the hepatic h-PRL receptors in female rats, and testosterone predominantly inhibits the induction of the hepatic lactogenic receptors in male rats.", "contents": "Sex difference in the induction of lactogenic receptors in rat livers. The relationship between serum levels of growth hormone (rGH), prolactin (rPRL), luteinizing hormone (rLH), follicle-stimulating hormone (rFSH), corticosterone, oestrogen, (oestradiol-17 beta) and testosterone and the hepatic binding sites specific to [125I]human-prolactin (h-PRL) were investigated in normal rats, in rats bearing the GH- and PRL-secreting tumour (GH3), and in rats 14 days after tumour removal. The presence of GH3 tumour elevated serum levels of rGH and rPRL and concomitantly increased the hepatic binding of [125I]h-PRL; the male rats had a greater increase than the female rats. The increased binding was due to an increase in the specific membrane binding sites, whereas the affinity constant (Ka) was not changed. In both male and female rats, there was a significant positive correlation between ser-m rGH levels (P less than 0.001) or serum rPRL (P less than 0.02) and specific binding of [125I]h-PRL in female rats only (P less than 0.02). In male rats, there was a significant negative correlation between serum testosterone levels and specific bindings of [125I]h-PRL (P less than 0.05). These results suggest that rGH and rPRL regulates the hepatic h-PRL receptors in female rats, and testosterone predominantly inhibits the induction of the hepatic lactogenic receptors in male rats."}
{"id": "PMID:229688", "title": "Hormonal effects on rat mammary gland in vitro.", "content": "The mammogenic and lactogenic effect of various hormones on rat mammary gland has been studied in vitro using an organ culture technique. The effects have been assessed mainly by light microscopy. The study has been confined mainly to the effects and interactions of the lactogenic protein hormones, corticosteroids and progesterone. It establishes the importance of the presence of insulin and serum and of the type of serum for the hormonal effects in vitro. These effects have been studied mainly on the explants obtained from 13 days pregnant rats. In addition explants from non-pregnant rats and at various stages of pregnancy and lactation were studied.", "contents": "Hormonal effects on rat mammary gland in vitro. The mammogenic and lactogenic effect of various hormones on rat mammary gland has been studied in vitro using an organ culture technique. The effects have been assessed mainly by light microscopy. The study has been confined mainly to the effects and interactions of the lactogenic protein hormones, corticosteroids and progesterone. It establishes the importance of the presence of insulin and serum and of the type of serum for the hormonal effects in vitro. These effects have been studied mainly on the explants obtained from 13 days pregnant rats. In addition explants from non-pregnant rats and at various stages of pregnancy and lactation were studied."}
{"id": "PMID:229693", "title": "Character of the gastric and duodenal electrical activity after blocking of the adrenoreactive structures.", "content": "Experiments are carried out on six dogs with chronically implanted electrodes in the gastric wall and in the duodenum. The electrical activity of the stomach (EGMG) and of the duodenum (EEG) is recorded. The myoelectrical complex of the stomach consists of four phases. The first phase records only slow potentials and lasts 40--60 min. The appearance of spike activity in the duodenum is always preceded by EGMG activation. Intravenous injection of the specific blocker of the alpha-adrenergic structures (phentolamine -- 1 mg/kg) leads to the appearance of spike activity in EGMG and EEG. 50--60 per cent of the slow waves being accompanied by spike potentials. At the same time the frequency of the slow potentials from EGMG is also decreased. Application of beta-adrenoblocker (propranolol -- 2 mg/kg) does not change subatantially EGMG and EEG. Simultaneous administration of alpha- and beta-adrenoblockers prolongs spiking time in the stomach and duodenum (spike potentials are recorded for 120--180 min, duration in the background 40--50 min). The influence of the interactions of cholinergic and adrenergic structures on the character of EGMG and EEG is discussed.", "contents": "Character of the gastric and duodenal electrical activity after blocking of the adrenoreactive structures. Experiments are carried out on six dogs with chronically implanted electrodes in the gastric wall and in the duodenum. The electrical activity of the stomach (EGMG) and of the duodenum (EEG) is recorded. The myoelectrical complex of the stomach consists of four phases. The first phase records only slow potentials and lasts 40--60 min. The appearance of spike activity in the duodenum is always preceded by EGMG activation. Intravenous injection of the specific blocker of the alpha-adrenergic structures (phentolamine -- 1 mg/kg) leads to the appearance of spike activity in EGMG and EEG. 50--60 per cent of the slow waves being accompanied by spike potentials. At the same time the frequency of the slow potentials from EGMG is also decreased. Application of beta-adrenoblocker (propranolol -- 2 mg/kg) does not change subatantially EGMG and EEG. Simultaneous administration of alpha- and beta-adrenoblockers prolongs spiking time in the stomach and duodenum (spike potentials are recorded for 120--180 min, duration in the background 40--50 min). The influence of the interactions of cholinergic and adrenergic structures on the character of EGMG and EEG is discussed."}
{"id": "PMID:229694", "title": "The neural control of the serotonin content in mammalian enterochromaffin cells.", "content": "Serotonin (5-HT) in the mammalian gut is mainly stored in enterochromaffin cells (EC). Vagal or splanchnic nerve stimulation respectively increase portal blood levels of 5-HT and decrease 5-HT content in EC, suggesting a neural control of these cells. Previous studies have also suggested that the vagal effect is mediated via vagal adrenergic nerve fibers, since this effect could be blocked by sympathectomy, removal of the superior cervical sympathetic ganglia or by the administration of a beta-adrenoceptor blocking agent, d, 1-propranolol. In the present study the control of the 5-HT content in EC was studied by a cytofluorimetric method in specimens from rat duodenal mucosa after drug incubations and transmural field stimulation (TFS) in vitro: Incubations in a Krebs' solution containing adrenaline (A), noradrenaline (NA) or isoprenaline (IP) (10(-9)--10(-5) M) caused a decrease of the 5-HT content in EC. For NA and A this effect was concentration-dependent. The effect of A was antagonized by d, 1-propranolol but not by d-propranolol, metoprolol, phentolamine or phenoxybenzamine. This indicates that the effects observed were mediated via a true beta-adrenoceptor mechanism. Acetylcholine (ACh), in the presence of eserine, also decreased the 5-HT content in EC, but was less potent than the adrenergic substances. TFS decreased the 5-HT content of EC to about 75% of unstimulated control levels. The presence of tetrodotoxin or d, 1-propranolol in the stimulation bath antagonized the effect of TFS. In specimens from rats pretreated with 6-OH-dopamine, TFS had no effect. Thus, TFS appears to induce a release of 5-HT from EC mainly by activation of adrenergic nerves. The ultrastructural relationship between nerve terminals and EC was studied in the guinea-pig duodenum. Animals were pretreated with 5-OH-dopamine in order to visualize adrenergic nerves. Near the base of most of the EC examined, at least 3 different types of nerve terminals were observed with the appearance of adrenergic, cholinergic and peptidergic terminals. In addition, dendrite-like processes were demonstrated. No true synapse on EC was found, but the minimal distance between the nerve terminals and EC was 150-250 nm, well within the limits of the \"autonomic gap\", suggesting a functional neural influence on these cells. The importance of the demonstrated beta-adrenergic control of EC was further studied in vivo. Efferent vagal nerve stimulation in the cat caused increased 5-HT levels in the portal plasma to more than twice the normal values after 15 min stimulation. Administration of the beta-adrenoceptor antagonist d, 1-propranolol in various doses did not abolish, but significantly reduced the response, particularly during the final part of the stimulation period. These results not only confirm a beta-adrenoceptor mediated release of 5-HT, but also suggest that other mechanisms are involved in the total response to vagal nerve stimulation.", "contents": "The neural control of the serotonin content in mammalian enterochromaffin cells. Serotonin (5-HT) in the mammalian gut is mainly stored in enterochromaffin cells (EC). Vagal or splanchnic nerve stimulation respectively increase portal blood levels of 5-HT and decrease 5-HT content in EC, suggesting a neural control of these cells. Previous studies have also suggested that the vagal effect is mediated via vagal adrenergic nerve fibers, since this effect could be blocked by sympathectomy, removal of the superior cervical sympathetic ganglia or by the administration of a beta-adrenoceptor blocking agent, d, 1-propranolol. In the present study the control of the 5-HT content in EC was studied by a cytofluorimetric method in specimens from rat duodenal mucosa after drug incubations and transmural field stimulation (TFS) in vitro: Incubations in a Krebs' solution containing adrenaline (A), noradrenaline (NA) or isoprenaline (IP) (10(-9)--10(-5) M) caused a decrease of the 5-HT content in EC. For NA and A this effect was concentration-dependent. The effect of A was antagonized by d, 1-propranolol but not by d-propranolol, metoprolol, phentolamine or phenoxybenzamine. This indicates that the effects observed were mediated via a true beta-adrenoceptor mechanism. Acetylcholine (ACh), in the presence of eserine, also decreased the 5-HT content in EC, but was less potent than the adrenergic substances. TFS decreased the 5-HT content of EC to about 75% of unstimulated control levels. The presence of tetrodotoxin or d, 1-propranolol in the stimulation bath antagonized the effect of TFS. In specimens from rats pretreated with 6-OH-dopamine, TFS had no effect. Thus, TFS appears to induce a release of 5-HT from EC mainly by activation of adrenergic nerves. The ultrastructural relationship between nerve terminals and EC was studied in the guinea-pig duodenum. Animals were pretreated with 5-OH-dopamine in order to visualize adrenergic nerves. Near the base of most of the EC examined, at least 3 different types of nerve terminals were observed with the appearance of adrenergic, cholinergic and peptidergic terminals. In addition, dendrite-like processes were demonstrated. No true synapse on EC was found, but the minimal distance between the nerve terminals and EC was 150-250 nm, well within the limits of the \"autonomic gap\", suggesting a functional neural influence on these cells. The importance of the demonstrated beta-adrenergic control of EC was further studied in vivo. Efferent vagal nerve stimulation in the cat caused increased 5-HT levels in the portal plasma to more than twice the normal values after 15 min stimulation. Administration of the beta-adrenoceptor antagonist d, 1-propranolol in various doses did not abolish, but significantly reduced the response, particularly during the final part of the stimulation period. These results not only confirm a beta-adrenoceptor mediated release of 5-HT, but also suggest that other mechanisms are involved in the total response to vagal nerve stimulation."}
{"id": "PMID:229695", "title": "Lipoprotein abnormalities in cholestasis. II. Isolation, characterization and clinical evaluation of an additional cholestatic lipoprotein (slow-migrating HDL).", "content": "An additional cholestatic lipoprotein with a slower mobility than the usual alpha-lipoprotein on polyacrylamide-gel disc-electrophoresis was found in the serum of patients with cholestasis. This abnormal lipoprotein was referred to as Slwo-migrating HDL (HDL-S), because it was mostly recovered in the high density lipoprotein (HDL) fraction after preparative ultracentrifugation. HDL-S was precipitated by dextran sulfate and Mg++ but did not react with either concanavalin A or anti-beta-lipoprotein serum. The main apoprotein of HDL-S was Apo A-I, and a trace of Apo E was also present. HDL-S was relatively enriched in free cholesterol and triglycerides and had a density in the range of 1.063 to 1.083. The appearance of HDL-S in serum or plasma was closely associated with chronic mild intrahepatic cholestasis, particularly as in primary biliary cirrhosis and related conditions.", "contents": "Lipoprotein abnormalities in cholestasis. II. Isolation, characterization and clinical evaluation of an additional cholestatic lipoprotein (slow-migrating HDL). An additional cholestatic lipoprotein with a slower mobility than the usual alpha-lipoprotein on polyacrylamide-gel disc-electrophoresis was found in the serum of patients with cholestasis. This abnormal lipoprotein was referred to as Slwo-migrating HDL (HDL-S), because it was mostly recovered in the high density lipoprotein (HDL) fraction after preparative ultracentrifugation. HDL-S was precipitated by dextran sulfate and Mg++ but did not react with either concanavalin A or anti-beta-lipoprotein serum. The main apoprotein of HDL-S was Apo A-I, and a trace of Apo E was also present. HDL-S was relatively enriched in free cholesterol and triglycerides and had a density in the range of 1.063 to 1.083. The appearance of HDL-S in serum or plasma was closely associated with chronic mild intrahepatic cholestasis, particularly as in primary biliary cirrhosis and related conditions."}
{"id": "PMID:229696", "title": "Decreased disappearance rate of 1-(2-tetrahydrofuryl)-5-fluorouracil (FT-207) from the blood and its unresponsiveness to tocophreyl nicotinate and indomethacin in patients with primary hepatocellular carcinoma.", "content": "The disappearance rates(K) of FT-207 from the blood in patients with primary hepatoma and advanced cirrhosis of the liver were significantly lower than those in control patients with cancer but normal liver function. Pretreatment with tocopheryl nicotinate and indomethacin increased the K values in the control subjects, but was without effect on the K values in patients with primary hepatoma.", "contents": "Decreased disappearance rate of 1-(2-tetrahydrofuryl)-5-fluorouracil (FT-207) from the blood and its unresponsiveness to tocophreyl nicotinate and indomethacin in patients with primary hepatocellular carcinoma. The disappearance rates(K) of FT-207 from the blood in patients with primary hepatoma and advanced cirrhosis of the liver were significantly lower than those in control patients with cancer but normal liver function. Pretreatment with tocopheryl nicotinate and indomethacin increased the K values in the control subjects, but was without effect on the K values in patients with primary hepatoma."}
{"id": "PMID:229698", "title": "Recent concepts in the conservative treatment of intracranial tumours in children.", "content": "The role of radiotherapy for certain intracranial tumours, given either postoperatively or as the sole treatment in inoperable cases, is discussed, principally in relation to medulloblastoma, ependymoma, cerebral astrocytoma, brain-stem glioma and craniopharyngioma. Methods of increasing the response of gliomas to irradiation are mentioned and reference is made to the possible value of chemotherapy and of immunotherapy as adjuvants against such tumours. Treatment results are reported and consideration given to the quality of long-term survival.", "contents": "Recent concepts in the conservative treatment of intracranial tumours in children. The role of radiotherapy for certain intracranial tumours, given either postoperatively or as the sole treatment in inoperable cases, is discussed, principally in relation to medulloblastoma, ependymoma, cerebral astrocytoma, brain-stem glioma and craniopharyngioma. Methods of increasing the response of gliomas to irradiation are mentioned and reference is made to the possible value of chemotherapy and of immunotherapy as adjuvants against such tumours. Treatment results are reported and consideration given to the quality of long-term survival."}
{"id": "PMID:229699", "title": "CSF levels of cyclic nucleotides in primary intracranial neoplasms: a preliminary report.", "content": "Recent evidence indicates that cyclic nucleotides are of importance for general and neurosurgical oncology, especially with respect to the contact-inhibition mechanisms and tumour cell growth. This preliminary report deals with the CSF levels of c-AMP and c-GMP in primary neoplasms in children and to problems related to the blood-brain barrier. Some cases of medulloblastoma were studied as well as a few cases of brain stem glioma and cystic astrocytoma. The importance of some rather unusual findings seems undebatable, i.e., the marked increase in c-GMP values usually observed in medulloblastoma and the decrease of c-AMP, that is fairly common in all malignant neoplasms. The main changes in the c-AMP/c-GMP ratio are also discussed.", "contents": "CSF levels of cyclic nucleotides in primary intracranial neoplasms: a preliminary report. Recent evidence indicates that cyclic nucleotides are of importance for general and neurosurgical oncology, especially with respect to the contact-inhibition mechanisms and tumour cell growth. This preliminary report deals with the CSF levels of c-AMP and c-GMP in primary neoplasms in children and to problems related to the blood-brain barrier. Some cases of medulloblastoma were studied as well as a few cases of brain stem glioma and cystic astrocytoma. The importance of some rather unusual findings seems undebatable, i.e., the marked increase in c-GMP values usually observed in medulloblastoma and the decrease of c-AMP, that is fairly common in all malignant neoplasms. The main changes in the c-AMP/c-GMP ratio are also discussed."}
{"id": "PMID:229700", "title": "Cerebral mixed tumour: osteo-condrosarcoma--glioblastoma multiforme.", "content": "A 49-year-old woman had a left frontal expanding mass with calcified areas. A craniotomy and resection of the mass were performed. Histological sections showed a mixed tumour: osteochondrosarcoma-glioblastoma multiforme. The absence of previous irradiation and its location, deep in the frontal lobe and apparently unattached to the meninges, add to the rarity of this association. A brief discussion concerning the presence of osseous or cartilaginous areas in brain tumours and the problem of cerebral mixed tumours follows the description of the case.", "contents": "Cerebral mixed tumour: osteo-condrosarcoma--glioblastoma multiforme. A 49-year-old woman had a left frontal expanding mass with calcified areas. A craniotomy and resection of the mass were performed. Histological sections showed a mixed tumour: osteochondrosarcoma-glioblastoma multiforme. The absence of previous irradiation and its location, deep in the frontal lobe and apparently unattached to the meninges, add to the rarity of this association. A brief discussion concerning the presence of osseous or cartilaginous areas in brain tumours and the problem of cerebral mixed tumours follows the description of the case."}
{"id": "PMID:229704", "title": "Endothelial cells and components of the kallikrein-kinin system.", "content": "Endothelial cells are a major source of kininase enzymes including kininase II. Kininase II is situated along the plasma membrane, not as an ecto-enzyme but as an enzyme synthesized by the endothelial cells themselves. However, it is likely that endothelial cells do more than degrade kinins. These cells are contractile and may possess kinin receptors; a possibility supported by the fact that kinins stimulate endothelial cells to form and release prostaglandin-related substances. In addition, we have found that endothelial cells in culture are reactive with antibodies to alpha 2-macroglobulin. Endothelial cells can hydrolyze [3H]Pro-Phe-Arg-anilide, a kallikrein substrate, but the reaction is not inhibited by soya bean trypsin inhibitor (SBTI) or Trasylol. Possibly kallikrein or a related trypsin-like enzyme is bound to alpha 2-macroglobulin and is not free to react with the inhibitors. Thus, endothelial cells can bind and inhibit kallikrein-like enzymes, degrade kinins and respond to kinin stimulation.", "contents": "Endothelial cells and components of the kallikrein-kinin system. Endothelial cells are a major source of kininase enzymes including kininase II. Kininase II is situated along the plasma membrane, not as an ecto-enzyme but as an enzyme synthesized by the endothelial cells themselves. However, it is likely that endothelial cells do more than degrade kinins. These cells are contractile and may possess kinin receptors; a possibility supported by the fact that kinins stimulate endothelial cells to form and release prostaglandin-related substances. In addition, we have found that endothelial cells in culture are reactive with antibodies to alpha 2-macroglobulin. Endothelial cells can hydrolyze [3H]Pro-Phe-Arg-anilide, a kallikrein substrate, but the reaction is not inhibited by soya bean trypsin inhibitor (SBTI) or Trasylol. Possibly kallikrein or a related trypsin-like enzyme is bound to alpha 2-macroglobulin and is not free to react with the inhibitors. Thus, endothelial cells can bind and inhibit kallikrein-like enzymes, degrade kinins and respond to kinin stimulation."}
{"id": "PMID:229706", "title": "The effect of human granulocyte proteinases on kininogens.", "content": "From the results obtained in preliminary in vitro experiments we may conclude that the unspecific breakdown of kininogens by neutral and acidic granulocytic proteinases may occur also in the organism during pathological conditions. Inhibitor application may serve as a valuable tool to prevent unspecific proteolytic degradation and thus elimination of kininogens and other clotting or complement factors from their biological function. Furthermore, specific cleavage products of the kininogens produced by granulocytic enzymes may be useful in the diagnosis of a beginning septicemia as well as in elucidation of the primary structure of the human kininogens.", "contents": "The effect of human granulocyte proteinases on kininogens. From the results obtained in preliminary in vitro experiments we may conclude that the unspecific breakdown of kininogens by neutral and acidic granulocytic proteinases may occur also in the organism during pathological conditions. Inhibitor application may serve as a valuable tool to prevent unspecific proteolytic degradation and thus elimination of kininogens and other clotting or complement factors from their biological function. Furthermore, specific cleavage products of the kininogens produced by granulocytic enzymes may be useful in the diagnosis of a beginning septicemia as well as in elucidation of the primary structure of the human kininogens."}
{"id": "PMID:229707", "title": "Comparative clinical study of FOY and Trasylol in acute pancreatitis.", "content": "In order to evaluate the efficacy and safety of FOY injectable ([ethyl-4-(6-guanidinohexanoyloxy) benzoate] methane sulfonate) on acute pancreatitis, a comparative clinical study was carried out using Trasylol as the control at 38 hospitals in Japan. Favourable results were obtained in 60 (71%) out of 84 patients in the FOY group and 29 (44%) out of 66 patients in the Trasylol group. The results showed that these both drugs were effective and the statistical analysis revealed considerable difference (X2 = 10.464, p less than 0.005) between the two groups in this condition of clinical trial. In addition, a double blind trial was carried out at 4 hospitals using FOY-305 ([n.n-dimethylcarbamoylmethy 4-(4-guanidinobenzoyloxy)-phenylacetate] methane sulfonate) oral capsule and inactive placebo. Favourable results were obtained in 18 (69%) out of 26 patients in the FOY-305 group and 8 (32%) out of 25 patients in the inactive placebo group, indicating a significant difference between the two groups (X2 = 8.930, p less than 0.01). The results of the present study suggest that synthetic protease inhibitor, FOY or FOY-305, is beneficial in the treatment of acute pancreatitis.", "contents": "Comparative clinical study of FOY and Trasylol in acute pancreatitis. In order to evaluate the efficacy and safety of FOY injectable ([ethyl-4-(6-guanidinohexanoyloxy) benzoate] methane sulfonate) on acute pancreatitis, a comparative clinical study was carried out using Trasylol as the control at 38 hospitals in Japan. Favourable results were obtained in 60 (71%) out of 84 patients in the FOY group and 29 (44%) out of 66 patients in the Trasylol group. The results showed that these both drugs were effective and the statistical analysis revealed considerable difference (X2 = 10.464, p less than 0.005) between the two groups in this condition of clinical trial. In addition, a double blind trial was carried out at 4 hospitals using FOY-305 ([n.n-dimethylcarbamoylmethy 4-(4-guanidinobenzoyloxy)-phenylacetate] methane sulfonate) oral capsule and inactive placebo. Favourable results were obtained in 18 (69%) out of 26 patients in the FOY-305 group and 8 (32%) out of 25 patients in the inactive placebo group, indicating a significant difference between the two groups (X2 = 8.930, p less than 0.01). The results of the present study suggest that synthetic protease inhibitor, FOY or FOY-305, is beneficial in the treatment of acute pancreatitis."}
{"id": "PMID:229708", "title": "Inhibitory effects of gabexate mesilate (FOY) on experimental DIC.", "content": "The inhibitory effects of a newly synthesized protease inhibitor, Gabexate mesilate (FOY), on experimental disseminated intravascular coagulation were studied as compared with those of aprotinin or heparin. Thrombin, tissue thromboplastin, and endotoxin were used as DIC trigger substances. As parameters on DIC, platelet counts, white blood cell counts, neutrophilic leukocyte counts, fibrinogen, fibrin degradation products, platelet retention, platelet aggregation, prothrombin time, partial thromboplastin time were served. The drug efficacy in each parameter were expressed by the score system and analyzed statistically. The results were summarized as follows; (1) In thrombin-induced DIC, FOY was apparently superior to the other drugs (p less than 0.05). (2) In thromboplastin-induced DIC, heparin was slightly more effective than FOY or aprotinin. (3) In endotoxin infusion, there were no significant differences among them. In conclusion, the results of the present study suggest that FOY was more effective than heparin or aprotinin on experimental DIC.", "contents": "Inhibitory effects of gabexate mesilate (FOY) on experimental DIC. The inhibitory effects of a newly synthesized protease inhibitor, Gabexate mesilate (FOY), on experimental disseminated intravascular coagulation were studied as compared with those of aprotinin or heparin. Thrombin, tissue thromboplastin, and endotoxin were used as DIC trigger substances. As parameters on DIC, platelet counts, white blood cell counts, neutrophilic leukocyte counts, fibrinogen, fibrin degradation products, platelet retention, platelet aggregation, prothrombin time, partial thromboplastin time were served. The drug efficacy in each parameter were expressed by the score system and analyzed statistically. The results were summarized as follows; (1) In thrombin-induced DIC, FOY was apparently superior to the other drugs (p less than 0.05). (2) In thromboplastin-induced DIC, heparin was slightly more effective than FOY or aprotinin. (3) In endotoxin infusion, there were no significant differences among them. In conclusion, the results of the present study suggest that FOY was more effective than heparin or aprotinin on experimental DIC."}
{"id": "PMID:229709", "title": "Effect of hypophysectomy upon renal kallikrein-kinin system in rats.", "content": "It is confirmed that urinary kallikrein is significantly and persistently decreased in totally hypophysectomized rats. In addition, kallikrein activity in the kidneys in these animals is significantly reduced (p less than .001) as compared to partially hypophysectomized and sham-operated rats. The administration of 125 mU of ACTH twice a day for 2 months, did not modify urinary kallikrein excretion. Negative effects were also obtained in subsequent periods, by injection of 10 microgram corticosterone and 10 microgram aldosterone, twice a day for 9 and 6 days, respectively. The administration of rat pituitary anterior lobe homogenates, freshly prepared, increased significantly urinary kallikrein level in hypophysectomized rats.", "contents": "Effect of hypophysectomy upon renal kallikrein-kinin system in rats. It is confirmed that urinary kallikrein is significantly and persistently decreased in totally hypophysectomized rats. In addition, kallikrein activity in the kidneys in these animals is significantly reduced (p less than .001) as compared to partially hypophysectomized and sham-operated rats. The administration of 125 mU of ACTH twice a day for 2 months, did not modify urinary kallikrein excretion. Negative effects were also obtained in subsequent periods, by injection of 10 microgram corticosterone and 10 microgram aldosterone, twice a day for 9 and 6 days, respectively. The administration of rat pituitary anterior lobe homogenates, freshly prepared, increased significantly urinary kallikrein level in hypophysectomized rats."}
{"id": "PMID:229710", "title": "Purification and properties of angiotensin I-converting enzyme in human lung and its role on the metabolism of vasoactive peptides in pulmonary circulation.", "content": "Purification of angiotensin I-converting enzyme from human lung and characteristics of the enzyme was studied. Experimental pneumonitis was produced in rabbits and the change of the activity of angiotensin I-converting enzyme was studied in purpose to clarify the role of this enzyme in the metabolism of vasoactive peptides in the lung. Purification was performed using trypsin treatment, acid treatment, DE52-cellulose column chromatography, hydroxyapatite chromatography and Sephadex G-200 gel filtration. The enzyme after final step showed a single band on disc gel electrophoresis. Experimental pneumonitis was produced by injection of Complete Freund's adjuvant (acute pneumonitis) and of N-nitroso-N-methylurethane (chronic pneumonitis). In acute experiment, angiotensin I-converting enzyme activity in pulmonary tissue and in plasma was significantly decreased. In perfusion experiment, conversion of angiotensin I to angiotensin II and inactivation of bradykinin were also significantly decreased. In case of decreased activity of angiotensin I-converting enzyme in the lung, less angiotensin II will be released into systemic circulation and bradykinin will pass through the pulmonary circulation into systemic circulation, thus this may result in the decrease of systemic blood pressure.", "contents": "Purification and properties of angiotensin I-converting enzyme in human lung and its role on the metabolism of vasoactive peptides in pulmonary circulation. Purification of angiotensin I-converting enzyme from human lung and characteristics of the enzyme was studied. Experimental pneumonitis was produced in rabbits and the change of the activity of angiotensin I-converting enzyme was studied in purpose to clarify the role of this enzyme in the metabolism of vasoactive peptides in the lung. Purification was performed using trypsin treatment, acid treatment, DE52-cellulose column chromatography, hydroxyapatite chromatography and Sephadex G-200 gel filtration. The enzyme after final step showed a single band on disc gel electrophoresis. Experimental pneumonitis was produced by injection of Complete Freund's adjuvant (acute pneumonitis) and of N-nitroso-N-methylurethane (chronic pneumonitis). In acute experiment, angiotensin I-converting enzyme activity in pulmonary tissue and in plasma was significantly decreased. In perfusion experiment, conversion of angiotensin I to angiotensin II and inactivation of bradykinin were also significantly decreased. In case of decreased activity of angiotensin I-converting enzyme in the lung, less angiotensin II will be released into systemic circulation and bradykinin will pass through the pulmonary circulation into systemic circulation, thus this may result in the decrease of systemic blood pressure."}
{"id": "PMID:229712", "title": "Relationship of human urinary and plasma kinins to sodium-retaining steroids and plasma renin activity.", "content": "In these studies we have shown that: 1. urinary kallikrein is an index of sodium-retaining steroid activity and may participate in the anti-natriuretic and kaliuretic effects of these hormones; 2. urinary kinin excretion is independent of changes in urinary kallikrein excretion; 3. levels of plasma bradykinin are highly correlated with levels of plasma renin activity probably because both respond to changes in extracellular fluid volume; and, 4. plasma bradykinin may act to antagonize angiotensin II to maintain normal blood pressure in hyper-reninemic states.", "contents": "Relationship of human urinary and plasma kinins to sodium-retaining steroids and plasma renin activity. In these studies we have shown that: 1. urinary kallikrein is an index of sodium-retaining steroid activity and may participate in the anti-natriuretic and kaliuretic effects of these hormones; 2. urinary kinin excretion is independent of changes in urinary kallikrein excretion; 3. levels of plasma bradykinin are highly correlated with levels of plasma renin activity probably because both respond to changes in extracellular fluid volume; and, 4. plasma bradykinin may act to antagonize angiotensin II to maintain normal blood pressure in hyper-reninemic states."}
{"id": "PMID:229713", "title": "Mammalian inhibitors of angiotensin converting enzyme (kininase II).", "content": "Urines and sera (human, guinea pig and rat) contain low molecular weight inhibitors of angiotensin converting enzyme (ACE). The urines contain ACE, but the enzyme is scarcely measurable without prior ultrafiltration or dialysis. The activity increases strikingly through three ultrafiltration steps using a membrane with a 10,000 MW retention limit. As implied, the ultrafiltrates contain inhibitory activity and can prevent the hydrolysis of [3H]benzoyl-Gly-His-Leu by ACE from any source, including lung and serum. Human urinary ultrafiltrate contains at least three inhibitors separable on Bio-Gel P-2. The inhibitors are acidic and can be partially purified on Bio-Rex 70 developed with an acetic acid gradient. The smallest of the inhibitors can be purified to apparent homogeneity by partition chromatography (sephadex G-25; butanol, acetic acid, H2O; 4:1:5). The excretion of inhibitory activity varies in response to dietary salt: Activity is low when rats are maintained on a high NaCl diet and is high (3 x's control) on a low NaCl diet. Thus, the activity of ACE may be modulated in vivo by naturally-occurring enzyme inhibitors. Whether some hypertensive patients are deficient in ACE inhibitory activity remains to be determined.", "contents": "Mammalian inhibitors of angiotensin converting enzyme (kininase II). Urines and sera (human, guinea pig and rat) contain low molecular weight inhibitors of angiotensin converting enzyme (ACE). The urines contain ACE, but the enzyme is scarcely measurable without prior ultrafiltration or dialysis. The activity increases strikingly through three ultrafiltration steps using a membrane with a 10,000 MW retention limit. As implied, the ultrafiltrates contain inhibitory activity and can prevent the hydrolysis of [3H]benzoyl-Gly-His-Leu by ACE from any source, including lung and serum. Human urinary ultrafiltrate contains at least three inhibitors separable on Bio-Gel P-2. The inhibitors are acidic and can be partially purified on Bio-Rex 70 developed with an acetic acid gradient. The smallest of the inhibitors can be purified to apparent homogeneity by partition chromatography (sephadex G-25; butanol, acetic acid, H2O; 4:1:5). The excretion of inhibitory activity varies in response to dietary salt: Activity is low when rats are maintained on a high NaCl diet and is high (3 x's control) on a low NaCl diet. Thus, the activity of ACE may be modulated in vivo by naturally-occurring enzyme inhibitors. Whether some hypertensive patients are deficient in ACE inhibitory activity remains to be determined."}
{"id": "PMID:229720", "title": "A postsynaptic inhibitory histamine H2-receptor in the mouse isolated vas deferens.", "content": "The effect of histamine on adrenergic neurotransmission in the mouse isolated vas deferens preparation was investigated. Concentrations of histamine ranging from 0.2 to 650 microM depressed, in a dose-related manner, not only the contractile response elicited by field stimulation but also the response caused by the addition of exogenous noradrenaline and acetylcholine. However, the release of [3H]-NA evoked by field stimulation or by high K+ remained unchanged in the presence of these concentrations of histamine. The inhibitory effect of histamine on the contractile responses caused by various stimuli was reduced or completely antagonized by cimetidine, a histamine H2-receptor antagonist but not by mepyramine, a conventional antihistamine. The inhibitory effect of histamine was found to be inversely proportional to both the Ca2+ concentration in the bathing medium and to the frequency of field stimulation. Further, the inhibitory effect of histamine was markedly reduced when Mg2+ was omitted from the bathing medium. It is concluded that the mouse vas deferens preparation contains a post-junctional inhibitory H2-receptor. The stimulation of H2-receptors by histamine inhibits the contractile response of the vas deferens, possibly by decreasing the availability of Ca2+ required for contraction by depressing the influx of Ca2+.", "contents": "A postsynaptic inhibitory histamine H2-receptor in the mouse isolated vas deferens. The effect of histamine on adrenergic neurotransmission in the mouse isolated vas deferens preparation was investigated. Concentrations of histamine ranging from 0.2 to 650 microM depressed, in a dose-related manner, not only the contractile response elicited by field stimulation but also the response caused by the addition of exogenous noradrenaline and acetylcholine. However, the release of [3H]-NA evoked by field stimulation or by high K+ remained unchanged in the presence of these concentrations of histamine. The inhibitory effect of histamine on the contractile responses caused by various stimuli was reduced or completely antagonized by cimetidine, a histamine H2-receptor antagonist but not by mepyramine, a conventional antihistamine. The inhibitory effect of histamine was found to be inversely proportional to both the Ca2+ concentration in the bathing medium and to the frequency of field stimulation. Further, the inhibitory effect of histamine was markedly reduced when Mg2+ was omitted from the bathing medium. It is concluded that the mouse vas deferens preparation contains a post-junctional inhibitory H2-receptor. The stimulation of H2-receptors by histamine inhibits the contractile response of the vas deferens, possibly by decreasing the availability of Ca2+ required for contraction by depressing the influx of Ca2+."}
{"id": "PMID:229721", "title": "Action of mannitol in various immunological experimental models.", "content": "The authors describe the inhibiting action of mannitol after repeated administration of low subcutaneous doses in a number of experimental immunological models. For example, in the rat it produces a reduction of the secondary arthritis of Freund's adjuvant polyarthritis and also of the pleurisy due to Bordetella pertussis hypersensitivity. In the mouse it reduces the reaction of delayed hypersensitivity to sheep red cells. Its action is also marked against ovalbumin-induced active skin anaphylaxis in the albino guinea-pig and on IgE synthesis in the rat. Moreover, after several injections it produces a reduction of carbon phagocytosis in the mouse. At the doses at which the effect appeared, no action could be found on various models of acute non-immune inflammation, diuresis, blood pressure, hematocrit and protein and plasma sodium levels.", "contents": "Action of mannitol in various immunological experimental models. The authors describe the inhibiting action of mannitol after repeated administration of low subcutaneous doses in a number of experimental immunological models. For example, in the rat it produces a reduction of the secondary arthritis of Freund's adjuvant polyarthritis and also of the pleurisy due to Bordetella pertussis hypersensitivity. In the mouse it reduces the reaction of delayed hypersensitivity to sheep red cells. Its action is also marked against ovalbumin-induced active skin anaphylaxis in the albino guinea-pig and on IgE synthesis in the rat. Moreover, after several injections it produces a reduction of carbon phagocytosis in the mouse. At the doses at which the effect appeared, no action could be found on various models of acute non-immune inflammation, diuresis, blood pressure, hematocrit and protein and plasma sodium levels."}
{"id": "PMID:229725", "title": "Solid and mucinous varieties of so-called mammary carcinoid tumors.", "content": "Three neoplasms that had histologic features reminiscent of carcinoid tumors of other sites were encountered in a review of 3,300 examples of invasive mammary cancer in women (.09%). One of these showed cytoplasmic argyrophilia. This, as well as the two putative carcinoids, lacked argentaffinity. Attention is directed to the occurence of variable numbers of argyrophilic cells in eight of 19 so-called mucinous cancers of the breast studied. Further, neurosecretory-type granules were observed in cells of all four mucinous cancers suitably prepared for electron microscopic examination. The possible reasons for the lack of universal argyrophilic reactions in these lesions is discussed. It is concluded that there may be two types of mammary carcinoid tumors, the solid and mucinous varieties. No patient who had the latter type had experienced treatment failure after five years of observation. Various numbers of ductal epithelial cells in four of 45 examples of banal fibrocystic disease showed cytoplasmic argyrophilia, and neurosecretory-type granules were found in two of eight examples suitably prepared for electron microscopic examination. Whether this demonstration establishes the existence of precursor elements for the development of the carcinoid tumors is at present uncertain.", "contents": "Solid and mucinous varieties of so-called mammary carcinoid tumors. Three neoplasms that had histologic features reminiscent of carcinoid tumors of other sites were encountered in a review of 3,300 examples of invasive mammary cancer in women (.09%). One of these showed cytoplasmic argyrophilia. This, as well as the two putative carcinoids, lacked argentaffinity. Attention is directed to the occurence of variable numbers of argyrophilic cells in eight of 19 so-called mucinous cancers of the breast studied. Further, neurosecretory-type granules were observed in cells of all four mucinous cancers suitably prepared for electron microscopic examination. The possible reasons for the lack of universal argyrophilic reactions in these lesions is discussed. It is concluded that there may be two types of mammary carcinoid tumors, the solid and mucinous varieties. No patient who had the latter type had experienced treatment failure after five years of observation. Various numbers of ductal epithelial cells in four of 45 examples of banal fibrocystic disease showed cytoplasmic argyrophilia, and neurosecretory-type granules were found in two of eight examples suitably prepared for electron microscopic examination. Whether this demonstration establishes the existence of precursor elements for the development of the carcinoid tumors is at present uncertain."}
{"id": "PMID:229726", "title": "Storage and transport of cultures for Herpes simplex virus, type 2.", "content": "Tryptic soy broth and brain-heart infusion broth maintained herpes simplex virus within +/- 1 serial dilution of the original titer in all of 51 samples held for one to three days at 4 C. In contrast, holding temperatures of -20 C or 22 C resulted in losses of titer of 10(2) or more. Holding periods as long as five days prior to inoculation did not delay the appearance of the cytopathic effect following inoculation. Unmodified tryptic soy broth or brain-heart infusion broth and holding periods as long as three days at 4 C prior to arrival in the laboratory give as satisfactory results as do traditional viral culture media and prompt inoculation of the specimen.", "contents": "Storage and transport of cultures for Herpes simplex virus, type 2. Tryptic soy broth and brain-heart infusion broth maintained herpes simplex virus within +/- 1 serial dilution of the original titer in all of 51 samples held for one to three days at 4 C. In contrast, holding temperatures of -20 C or 22 C resulted in losses of titer of 10(2) or more. Holding periods as long as five days prior to inoculation did not delay the appearance of the cytopathic effect following inoculation. Unmodified tryptic soy broth or brain-heart infusion broth and holding periods as long as three days at 4 C prior to arrival in the laboratory give as satisfactory results as do traditional viral culture media and prompt inoculation of the specimen."}
{"id": "PMID:229727", "title": "Transfer of measles, mumps, and rubella antibodies from mother to infant. Its effect on measles, mumps, and rubella immunization.", "content": "Sera from 42 mother-infant pairs were examined to determine the effect of passively acquired enhanced neutralizing (ENt) antibody on immunization. The ENt antibodies to measles, mumps, and rubella were greater in term newborns than in their mothers, with mean ratio of 1.8:1, 1.3:1, and 1.2:1, respectively. In 21% to 25% of the children, these antibodies persisted until 12 months of age. When immunized with trivalent measles-mumps-rubella vaccine, children who had persisting ENt measles and rubella titers had significantly lower mean antibody responses than children without detectable antibodies to the two viruses. Persisting ENt mumps antibodies did not affect the postimmunization titers. Seroconversion rates to any of the three viruses were not different in children with or without preexisting ENt antibody.", "contents": "Transfer of measles, mumps, and rubella antibodies from mother to infant. Its effect on measles, mumps, and rubella immunization. Sera from 42 mother-infant pairs were examined to determine the effect of passively acquired enhanced neutralizing (ENt) antibody on immunization. The ENt antibodies to measles, mumps, and rubella were greater in term newborns than in their mothers, with mean ratio of 1.8:1, 1.3:1, and 1.2:1, respectively. In 21% to 25% of the children, these antibodies persisted until 12 months of age. When immunized with trivalent measles-mumps-rubella vaccine, children who had persisting ENt measles and rubella titers had significantly lower mean antibody responses than children without detectable antibodies to the two viruses. Persisting ENt mumps antibodies did not affect the postimmunization titers. Seroconversion rates to any of the three viruses were not different in children with or without preexisting ENt antibody."}
{"id": "PMID:229729", "title": "Vitamin D metabolism and calcium absorption.", "content": "Vitamin D along with parathyroid hormone (PTH) and calcitonin (CT) are the three principal effectors of calcium and phosphorus homeostasis. The secosteroid, vitamin D3, is subject to metabolic conversion to its biologically active form(s) 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] prior to initiation of its physiologic responses in the intestine and skeletal system. The production of 1,25(OH)2D3 is stringently regulated by a variety of endocrine signals including PTH as well as the \"calcium needs\" of the organism. At the target intestine, 1,25-(OH)2D3 stimulates the intestinal absorption of calcium via a mechanism analogous to that of other steroid hormones. Definitive biochemical evidence exists supporting the existence in the intestine of a highly specific protein receptor for 1,25(OH)2D3. After formation of the steroid-receptor complex, it migrates to the nucleus of the cell and stimulates messenger-RNA synthesis for proteins (including a calcium-binding protein) which are necessary for the generation of the biologic response. Current efforts to biochemically characterize vitamin D-mediated intestinal calcium transport include efforts to understand the role of calcium-binding protein in this process, as well as to identify other protein components present either in the brush border or basal lateral membranes.", "contents": "Vitamin D metabolism and calcium absorption. Vitamin D along with parathyroid hormone (PTH) and calcitonin (CT) are the three principal effectors of calcium and phosphorus homeostasis. The secosteroid, vitamin D3, is subject to metabolic conversion to its biologically active form(s) 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] prior to initiation of its physiologic responses in the intestine and skeletal system. The production of 1,25(OH)2D3 is stringently regulated by a variety of endocrine signals including PTH as well as the \"calcium needs\" of the organism. At the target intestine, 1,25-(OH)2D3 stimulates the intestinal absorption of calcium via a mechanism analogous to that of other steroid hormones. Definitive biochemical evidence exists supporting the existence in the intestine of a highly specific protein receptor for 1,25(OH)2D3. After formation of the steroid-receptor complex, it migrates to the nucleus of the cell and stimulates messenger-RNA synthesis for proteins (including a calcium-binding protein) which are necessary for the generation of the biologic response. Current efforts to biochemically characterize vitamin D-mediated intestinal calcium transport include efforts to understand the role of calcium-binding protein in this process, as well as to identify other protein components present either in the brush border or basal lateral membranes."}
{"id": "PMID:229731", "title": "Pectoralis major muscle defect and Poland complex.", "content": "Pectoralis major muscle defect (PMD) was diagnosed in 27 infants from a series of 599,109 live births in South America (1/22,189). In all 27 cases the PMD was unilateral, mainly affecting the right side (20/27), and there were more male (19/27) than female cases. No familial cases and no parental consanguinity were recorded. A positive correlation was observed between PMD and sex hormone intake and vaginal bleeding in the first trimester of pregnancy. In 12 (1/49,925) of the 27 PMD cases hypoplasia and/or syndactyly of the ipsilateral hand was also diagnosed. The index-middle interdigital space was affected in all 11 cases with symbrachydactyly. Additional congenital anomalies were observed in 4/27 cases, and they were: hemangiomas, hypospadias, and clubfeet. Poland complex (12 cases), isolated PMD (15 cases), and isolated symbrachydactyly (18 cases), showed a similar pattern for symmetry, sidedness, syndactyly type, and sex ratio.", "contents": "Pectoralis major muscle defect and Poland complex. Pectoralis major muscle defect (PMD) was diagnosed in 27 infants from a series of 599,109 live births in South America (1/22,189). In all 27 cases the PMD was unilateral, mainly affecting the right side (20/27), and there were more male (19/27) than female cases. No familial cases and no parental consanguinity were recorded. A positive correlation was observed between PMD and sex hormone intake and vaginal bleeding in the first trimester of pregnancy. In 12 (1/49,925) of the 27 PMD cases hypoplasia and/or syndactyly of the ipsilateral hand was also diagnosed. The index-middle interdigital space was affected in all 11 cases with symbrachydactyly. Additional congenital anomalies were observed in 4/27 cases, and they were: hemangiomas, hypospadias, and clubfeet. Poland complex (12 cases), isolated PMD (15 cases), and isolated symbrachydactyly (18 cases), showed a similar pattern for symmetry, sidedness, syndactyly type, and sex ratio."}
{"id": "PMID:229732", "title": "Bilateral cytomegalovirus panuveitis after high-dose corticosteroid therapy.", "content": "A 30-year-old previously healthy woman who recieved immunosuppressive doses of corticosteroids developed an unusual culture-proved cytomegalovirus panuveitis bilaterally. The atypical clinical course was marked by bilateral exudative detachements with minimal evidence of retinitis. Any patient receiving blood transfusions and immunosuppressive doses of corticosteroids is potentially at risk for developing ocular cytomegalovirus infection, and the clinical presentation of the ocular infection may be atypical.", "contents": "Bilateral cytomegalovirus panuveitis after high-dose corticosteroid therapy. A 30-year-old previously healthy woman who recieved immunosuppressive doses of corticosteroids developed an unusual culture-proved cytomegalovirus panuveitis bilaterally. The atypical clinical course was marked by bilateral exudative detachements with minimal evidence of retinitis. Any patient receiving blood transfusions and immunosuppressive doses of corticosteroids is potentially at risk for developing ocular cytomegalovirus infection, and the clinical presentation of the ocular infection may be atypical."}
{"id": "PMID:229733", "title": "Developments in the identification of human skeletal material (1968-1978).", "content": "A review of publications over the last ten years of methods in the field of physical anthropology for determining age, sex, race and stature of human skeletal material is presented. Comparisons are made with the types of papers published in the previous ten years (1958-1968) in six categories: (1) Visual examination of bones (2) Anthropometric measurements of bones (3) Anthropometric measurements with subsequent use of statistics in the form of discriminate function analyses (4) Time and sequence of eruption of the teeth (5) X-ray examination of the internal structure of bone sections (6) Microscopic examination of the internal structure of bone.", "contents": "Developments in the identification of human skeletal material (1968-1978). A review of publications over the last ten years of methods in the field of physical anthropology for determining age, sex, race and stature of human skeletal material is presented. Comparisons are made with the types of papers published in the previous ten years (1958-1968) in six categories: (1) Visual examination of bones (2) Anthropometric measurements of bones (3) Anthropometric measurements with subsequent use of statistics in the form of discriminate function analyses (4) Time and sequence of eruption of the teeth (5) X-ray examination of the internal structure of bone sections (6) Microscopic examination of the internal structure of bone."}
{"id": "PMID:229730", "title": "Urinary free cortisol excretion in patients with metastatic cancer.", "content": "Many patients with metastatic carcinoma have an increase in urinary excretion of 17-hydroxycorticosteroids (17-OHCS), plasma concentrations of 17-OHCS, plasma total cortisol, plasma nonprotein-bound cortisol, or cortisol production rate. A small portion of circulating cortisol is excreted in the urine as unaltered or free cortisol. This urinary free cortisol, which is believed to reflect the average unbound plasma cortisol circulating during the day, is an excellent measure of adrenal cortical function. In this study, we compared the urinary free cortisol of 35 patients with metastastic cancer (10 small cell carcinomas of the lung, 8 other types of carcinoma of the lung, 8 breast carcinomas, and a miscellaneous carcinomas) with a group of 15 healthy age-matched volunteers. There were no significant changes in urinary free cortisol excretion in the patients with cancer.", "contents": "Urinary free cortisol excretion in patients with metastatic cancer. Many patients with metastatic carcinoma have an increase in urinary excretion of 17-hydroxycorticosteroids (17-OHCS), plasma concentrations of 17-OHCS, plasma total cortisol, plasma nonprotein-bound cortisol, or cortisol production rate. A small portion of circulating cortisol is excreted in the urine as unaltered or free cortisol. This urinary free cortisol, which is believed to reflect the average unbound plasma cortisol circulating during the day, is an excellent measure of adrenal cortical function. In this study, we compared the urinary free cortisol of 35 patients with metastastic cancer (10 small cell carcinomas of the lung, 8 other types of carcinoma of the lung, 8 breast carcinomas, and a miscellaneous carcinomas) with a group of 15 healthy age-matched volunteers. There were no significant changes in urinary free cortisol excretion in the patients with cancer."}
{"id": "PMID:229735", "title": "Effect of ACTH on the aldosterone response to potassium in sheep with adrenal transplants.", "content": "The importance of physiological ACTH stimulation in maintaining the response of aldosterone secretion to potassium was studied in 5 conscious sheep with cervical adrenal autotransplants. Endogenous ACTH secretion was suppressed by dexamethasone. Constant local infusions of potassium that raised adrenal venous plasma by 2 mmol/l increased aldosterone secretion from 3 +/- 1 ng/min (mean +/- SE) to levels of 50 +/- 13 ng/min at 30 min, after which secretion fell to 14 +/- 6 ng/min at 230 min. Addition of submaximal ACTH (0.04 - 0.10 mU/min) to potassium infusions produced similar responses at 0--130 min, but aldosterone secretion increased at 130--190 min and was more sustained (40 +/- 9 ng/min at 230 min; P less than 0.05). Infusions of submaximal ACTH alone did not significantly increase aldosterone secretion above basal levels. Infusions of maximal ACTH (16.6 mU/min) produced higher aldosterone secretion in the group given ACTH replacement. These results show that the aldosterone response to potassium is phasic and poorly sustained in the absence of ACTH. Responsiveness can be restored by doses of ACTH insufficient alone to stimulate aldosterone secretion.", "contents": "Effect of ACTH on the aldosterone response to potassium in sheep with adrenal transplants. The importance of physiological ACTH stimulation in maintaining the response of aldosterone secretion to potassium was studied in 5 conscious sheep with cervical adrenal autotransplants. Endogenous ACTH secretion was suppressed by dexamethasone. Constant local infusions of potassium that raised adrenal venous plasma by 2 mmol/l increased aldosterone secretion from 3 +/- 1 ng/min (mean +/- SE) to levels of 50 +/- 13 ng/min at 30 min, after which secretion fell to 14 +/- 6 ng/min at 230 min. Addition of submaximal ACTH (0.04 - 0.10 mU/min) to potassium infusions produced similar responses at 0--130 min, but aldosterone secretion increased at 130--190 min and was more sustained (40 +/- 9 ng/min at 230 min; P less than 0.05). Infusions of submaximal ACTH alone did not significantly increase aldosterone secretion above basal levels. Infusions of maximal ACTH (16.6 mU/min) produced higher aldosterone secretion in the group given ACTH replacement. These results show that the aldosterone response to potassium is phasic and poorly sustained in the absence of ACTH. Responsiveness can be restored by doses of ACTH insufficient alone to stimulate aldosterone secretion."}
{"id": "PMID:229736", "title": "Physiological basis for absorptive and renal hypercalciurias.", "content": "Idiopathic hypercalciuria constitutes two major variants-absorptive hypercalciuria, characterized by a primary intestinal hyperabsorption of calcium, and renal hypercalciuria, in which renal tubular reabsorption of calcium is primarily impaired. The two forms of hypercalciuria may be distinguished from each other, since a) parathyroid function is stimualted in renal hypercalciuria, but normal or suppressed in absorptive hypercalciuria, b) the renal leak of calcium is present in renal hypercalciuria, but not in absorptive hypercalciuria, c) intestinal calcium absorption is probably increased primarily in absorptive hypercalciuria, and secondarily in renal hypercalciuria (from parathyroid hormone excess), d) the increased calcium absorption in renal hypercalciuria probably results from the parathyroid hormone-dependent stimulation of 1,25-dihydroxyvitamin D synthesis, whereas that in absorptive hypercalciuria may be vitamin D-independent, e) the response of the two conditions to certain treatments is unique, and f) the sequelae of parathyroid hormone excess, such as low bone density and negative calcium balance, may be present in renal hypercalciuria, but not in absorptive hypercalciuria. These findings provide a physiological basis for the consideration of absorptive and renal hypercalciurias as distinct and separate entities.", "contents": "Physiological basis for absorptive and renal hypercalciurias. Idiopathic hypercalciuria constitutes two major variants-absorptive hypercalciuria, characterized by a primary intestinal hyperabsorption of calcium, and renal hypercalciuria, in which renal tubular reabsorption of calcium is primarily impaired. The two forms of hypercalciuria may be distinguished from each other, since a) parathyroid function is stimualted in renal hypercalciuria, but normal or suppressed in absorptive hypercalciuria, b) the renal leak of calcium is present in renal hypercalciuria, but not in absorptive hypercalciuria, c) intestinal calcium absorption is probably increased primarily in absorptive hypercalciuria, and secondarily in renal hypercalciuria (from parathyroid hormone excess), d) the increased calcium absorption in renal hypercalciuria probably results from the parathyroid hormone-dependent stimulation of 1,25-dihydroxyvitamin D synthesis, whereas that in absorptive hypercalciuria may be vitamin D-independent, e) the response of the two conditions to certain treatments is unique, and f) the sequelae of parathyroid hormone excess, such as low bone density and negative calcium balance, may be present in renal hypercalciuria, but not in absorptive hypercalciuria. These findings provide a physiological basis for the consideration of absorptive and renal hypercalciurias as distinct and separate entities."}
{"id": "PMID:229737", "title": "Indirect evidence for enhancement of Na-K-ATPase activity with stimulation of rectal gland secretion.", "content": "The relation between active chloride secretion and Na-K-ATPase activity was studied in the isolated perfused rectal gland of Squalus acanthias stimulated by cAMP and theophylline. Ouabain inhibited both secretion and oxygen uptake in stimulated glands. Stimulation of chloride secretion by cAMP and theophylline resulted in a six- to sevenfold rise in ouabain-inhibitable oxygen consumption. Intracellular sodium concentration decreased while intracellular potassium rose. These findings suggest activation of Na-K-ATPase. On the other hand, the activity of Na-K-ATPase in whole homogenates of rectal gland tissue was not increased after cAMP stimulation of the perfused gland, nor was ouabain binding increased. Calculated intracellular chloride concentration fell after secretion was stimulated in a way consistent with an action of cAMP to increase luminal permeability to chloride.", "contents": "Indirect evidence for enhancement of Na-K-ATPase activity with stimulation of rectal gland secretion. The relation between active chloride secretion and Na-K-ATPase activity was studied in the isolated perfused rectal gland of Squalus acanthias stimulated by cAMP and theophylline. Ouabain inhibited both secretion and oxygen uptake in stimulated glands. Stimulation of chloride secretion by cAMP and theophylline resulted in a six- to sevenfold rise in ouabain-inhibitable oxygen consumption. Intracellular sodium concentration decreased while intracellular potassium rose. These findings suggest activation of Na-K-ATPase. On the other hand, the activity of Na-K-ATPase in whole homogenates of rectal gland tissue was not increased after cAMP stimulation of the perfused gland, nor was ouabain binding increased. Calculated intracellular chloride concentration fell after secretion was stimulated in a way consistent with an action of cAMP to increase luminal permeability to chloride."}
{"id": "PMID:229739", "title": "Mixed neuromuscular block. A re-assessment using train-of-four stimulation.", "content": "Suxamethonium was administered to patients during recovery from non-depolarising muscle relaxation. The effect of suxamethonium varied depending upon the degree of recovery from the non-depolarising block when it was administered. Early in recovery suxamethonium produced reversal of the non-depolarising block without paralysis whereas when administered later, initial recovery of the non-depolarising block was followed by paralysis. If administered after 50% recovery the predominant effect was paralysis without initial recovery. Assessment of neuromuscular blockade with train-of-four stimulation showed that the paralysis produced by suxamethonium under these circumstances, had depolarising and non-depolarising features.", "contents": "Mixed neuromuscular block. A re-assessment using train-of-four stimulation. Suxamethonium was administered to patients during recovery from non-depolarising muscle relaxation. The effect of suxamethonium varied depending upon the degree of recovery from the non-depolarising block when it was administered. Early in recovery suxamethonium produced reversal of the non-depolarising block without paralysis whereas when administered later, initial recovery of the non-depolarising block was followed by paralysis. If administered after 50% recovery the predominant effect was paralysis without initial recovery. Assessment of neuromuscular blockade with train-of-four stimulation showed that the paralysis produced by suxamethonium under these circumstances, had depolarising and non-depolarising features."}
{"id": "PMID:229744", "title": "Pathogenesis of swine vesicular disease in pigs.", "content": "Pigs exposed to swine vesicular disease virus developed vesicular lesions by postinoculation day 2. Lesions first appeared on the coronary band and then on the dewclaw, tongue, snout, lips, and bulbs of the heels. The onset of viremia coincided with febrile response and the appearance of vesicles. Virus was isolated from the nasal discharge, esophageal-pharyngeal fluid, and feces as early as postinoculation day 1. Greater amounts of virus were isolated from samples collected during the first week of infection, and lesser amounts from samples collected during the second week. The appearance and the distribution of specific fluorescence in various tissues indicated that during the development of swine vesicular disease virus infection, the epithelial tissues were initially involved, followed by a generalized infection of lymph tissues, and subsequently, a primary viremia. Seroconversion was detectable as early as postinoculation day 4. A mild nonsuppurative meningoencephalomyelitis throughout the CNS was observed in both inoculated and contact-exposed pigs. The olfactory bulbs were most severely and were frequently affected, particularly in contact pigs. The most severe brain lesions were found in pigs 3 to 4 days after the onset of viremia; contact pigs showed more severe brain lesions than inoculated pigs. Microscopic changes were also found in the coronary band, snout, tongue, and heart.", "contents": "Pathogenesis of swine vesicular disease in pigs. Pigs exposed to swine vesicular disease virus developed vesicular lesions by postinoculation day 2. Lesions first appeared on the coronary band and then on the dewclaw, tongue, snout, lips, and bulbs of the heels. The onset of viremia coincided with febrile response and the appearance of vesicles. Virus was isolated from the nasal discharge, esophageal-pharyngeal fluid, and feces as early as postinoculation day 1. Greater amounts of virus were isolated from samples collected during the first week of infection, and lesser amounts from samples collected during the second week. The appearance and the distribution of specific fluorescence in various tissues indicated that during the development of swine vesicular disease virus infection, the epithelial tissues were initially involved, followed by a generalized infection of lymph tissues, and subsequently, a primary viremia. Seroconversion was detectable as early as postinoculation day 4. A mild nonsuppurative meningoencephalomyelitis throughout the CNS was observed in both inoculated and contact-exposed pigs. The olfactory bulbs were most severely and were frequently affected, particularly in contact pigs. The most severe brain lesions were found in pigs 3 to 4 days after the onset of viremia; contact pigs showed more severe brain lesions than inoculated pigs. Microscopic changes were also found in the coronary band, snout, tongue, and heart."}
{"id": "PMID:229740", "title": "Reversal of pancuronium with edrophonium.", "content": "Edrophonium was administered as a bolus of 2, 10 or 50 mg (0.03, 0.14 and 0.71 mg/kg) to antagonize neuromuscular block after pancuronium in man. Neuromuscular transmission was measured using \"train-of-four\" stimulation. Recovery started within 1 min, was maximum at 2 min and was then followed by a plateau of slow continued improvement. The degree of recovery increased with larger doses of edrophonium and also was related to the total amount of pancuronium administered although reversal was attempted at the same degree of spontaneous recovery. There was no evidence of recurarisation or depolarising block.", "contents": "Reversal of pancuronium with edrophonium. Edrophonium was administered as a bolus of 2, 10 or 50 mg (0.03, 0.14 and 0.71 mg/kg) to antagonize neuromuscular block after pancuronium in man. Neuromuscular transmission was measured using \"train-of-four\" stimulation. Recovery started within 1 min, was maximum at 2 min and was then followed by a plateau of slow continued improvement. The degree of recovery increased with larger doses of edrophonium and also was related to the total amount of pancuronium administered although reversal was attempted at the same degree of spontaneous recovery. There was no evidence of recurarisation or depolarising block."}
{"id": "PMID:229745", "title": "Transmissible gastroenteritis in neonatal dogs: experimental intestinal infection with transmissible gastroenteritis virus.", "content": "Fourteen neonatal dogs (4 through 11 days of age) were exposed orally to the Purdue strain of transmissible gastroenteritis (TGE) virus, and six dogs of similar age were noninoculated controls. Clinical signs of enteric disease did not develop. Both exposed and control dogs had normal fecal passages and appetite throughout the experiment. Jejunal epithelium from dogs euthanatized at 12, 24, 48, and 96 hours and at 10 days after exposure did not exhibit morphologic alterations detectable by light microscopy. Electron microscopic examination indicated that jejunal epithelial cells contained TGE viral particles as early as 12 hours after dogs were exposed. There were no apparent morphologic alterations or signs of desquamation of virus-infected cells, however. Results of pig transmission studies indicated that viable TGE virus was in jejunal tissue of the dogs as early as 12 hours and as late as 10 days after exposure to the virus.", "contents": "Transmissible gastroenteritis in neonatal dogs: experimental intestinal infection with transmissible gastroenteritis virus. Fourteen neonatal dogs (4 through 11 days of age) were exposed orally to the Purdue strain of transmissible gastroenteritis (TGE) virus, and six dogs of similar age were noninoculated controls. Clinical signs of enteric disease did not develop. Both exposed and control dogs had normal fecal passages and appetite throughout the experiment. Jejunal epithelium from dogs euthanatized at 12, 24, 48, and 96 hours and at 10 days after exposure did not exhibit morphologic alterations detectable by light microscopy. Electron microscopic examination indicated that jejunal epithelial cells contained TGE viral particles as early as 12 hours after dogs were exposed. There were no apparent morphologic alterations or signs of desquamation of virus-infected cells, however. Results of pig transmission studies indicated that viable TGE virus was in jejunal tissue of the dogs as early as 12 hours and as late as 10 days after exposure to the virus."}
{"id": "PMID:229746", "title": "Three serologic types of adenovirus infections of owl monkeys.", "content": "From a colony of 131 owl monkeys, adenovirus was isolated 68 times from 433 oropharyngeal and rectal swab sample pairs collected over a 2-year period. A total of 63 of 68 adenovirus isolates were grouped by neutralization into 1 of 3 types designated owl monkey adenovirus types (OMAV Ty) I, II, and III. The OMAV Ty I and Ty II were identified by neutralization with antiserum to squirrel monkey adenovirus type I and adenovirus SV-11, respectively. The OMAV Ty III was partially neutralized by antiserum to OMAV Ty II. The OMAV Ty I was isolated from 8 of 30 newly imported owl monkeys within 3 weeks of arrival. A total of 13 of 26 owl monkeys had a fourfold or greater rise in serum-neutralization (SN) titer with 25 of 27 developing SN titers of greater than or equal to 1:80. A total of 40 of 87 other owl monkeys in the colony had SN titers of greater than or equal to 1:5. The OMAV Ty II was isolated from 51 (12%) of 433 swab samples pairs. Virus was isolated from 26 owl monkeys with 13 having persistent infections. Viral isolations spanned a 10- to 17-month period for five of these owl monkeys. In 114 owl monkeys, 101 (86%) had SN titers to OMAV Ty II greater than or equal to 1:20. The OMAV Ty III was isolated from three owl monkeys. Of 114 owl monkeys, 93 (82%) had SN titers to OMAV Ty III of greater than or equal to 1:20. Although the distribution of SN titers were similar for OMAV Ty II and Ty III, 42 (37%) of 114 owl monkeys had eightfold or greater differences in SN titers between OMAV Ty II and Ty III.", "contents": "Three serologic types of adenovirus infections of owl monkeys. From a colony of 131 owl monkeys, adenovirus was isolated 68 times from 433 oropharyngeal and rectal swab sample pairs collected over a 2-year period. A total of 63 of 68 adenovirus isolates were grouped by neutralization into 1 of 3 types designated owl monkey adenovirus types (OMAV Ty) I, II, and III. The OMAV Ty I and Ty II were identified by neutralization with antiserum to squirrel monkey adenovirus type I and adenovirus SV-11, respectively. The OMAV Ty III was partially neutralized by antiserum to OMAV Ty II. The OMAV Ty I was isolated from 8 of 30 newly imported owl monkeys within 3 weeks of arrival. A total of 13 of 26 owl monkeys had a fourfold or greater rise in serum-neutralization (SN) titer with 25 of 27 developing SN titers of greater than or equal to 1:80. A total of 40 of 87 other owl monkeys in the colony had SN titers of greater than or equal to 1:5. The OMAV Ty II was isolated from 51 (12%) of 433 swab samples pairs. Virus was isolated from 26 owl monkeys with 13 having persistent infections. Viral isolations spanned a 10- to 17-month period for five of these owl monkeys. In 114 owl monkeys, 101 (86%) had SN titers to OMAV Ty II greater than or equal to 1:20. The OMAV Ty III was isolated from three owl monkeys. Of 114 owl monkeys, 93 (82%) had SN titers to OMAV Ty III of greater than or equal to 1:20. Although the distribution of SN titers were similar for OMAV Ty II and Ty III, 42 (37%) of 114 owl monkeys had eightfold or greater differences in SN titers between OMAV Ty II and Ty III."}
{"id": "PMID:229747", "title": "Comparative pathogenesis studies with oncogenic and nononcogenic Marek's disease viruses and turkey herpesvirus.", "content": "An apparently nononcogenic Marek's disease virus (SB-1) and turkey herpesvirus could be readily isolated from spleen, bursa of Fabricius, thymus, and peripheral blood lymphocytes of chickens beginning 4 to 6 days after inoculation, but unlike infections with two isolates of oncogenic Marek's disease virus (JM-10 and CU-2), virus replication in these cells was rare, and necrosis in the organs was essentially absent. Splenic enlargement was observed regularly during the first 4 to 11 days after inoculation, and Marek's disease tumor-associated surface antigen was observed on splenic and other lymphocytes in the four viral inoculation groups. Cellular cytotoxicity of splenic lymphocytes was demonstrated in vitro with cultured Marek's disease tumor cells (MSB-1 lymphoblastoid cell line) as the target in a chromium-release assay. The four viral infections induced sensitized lymphocytes.", "contents": "Comparative pathogenesis studies with oncogenic and nononcogenic Marek's disease viruses and turkey herpesvirus. An apparently nononcogenic Marek's disease virus (SB-1) and turkey herpesvirus could be readily isolated from spleen, bursa of Fabricius, thymus, and peripheral blood lymphocytes of chickens beginning 4 to 6 days after inoculation, but unlike infections with two isolates of oncogenic Marek's disease virus (JM-10 and CU-2), virus replication in these cells was rare, and necrosis in the organs was essentially absent. Splenic enlargement was observed regularly during the first 4 to 11 days after inoculation, and Marek's disease tumor-associated surface antigen was observed on splenic and other lymphocytes in the four viral inoculation groups. Cellular cytotoxicity of splenic lymphocytes was demonstrated in vitro with cultured Marek's disease tumor cells (MSB-1 lymphoblastoid cell line) as the target in a chromium-release assay. The four viral infections induced sensitized lymphocytes."}
{"id": "PMID:229748", "title": "Inhibition and enhancement of avian adenovirus plaque production by heavy and light avian adenovirus-associated viral particles.", "content": "The effect of heavy and light avian adenovirus-associated viral (A-AV) particles on the replication of several adenovirus serotypes was studied in chicken embryo kidney cells. There was a significant decrease (P less than 0.05) in the number and size of adenovirus-induced plaques at A-AV multiplicities of infection greater than 40. Enhancement of plaque production was observed when A-AV multiplicities of infection were 1 to 40. There was a significant increase in the number and size of infective centers. Analysis of cellular yields indicated an increase in the number of adenoviruses produced per cell. Heavy A-AV particles of buoyant density 1.42 g/cm3 in CsCl were found to enhance plaque production more than light particles (1.38 g/cm3). Conversely, light particles showed greater inhibition of plaque production. Adenovirus serotypes varied in their response to enhancement or inhibition by A-AV particles of different density.", "contents": "Inhibition and enhancement of avian adenovirus plaque production by heavy and light avian adenovirus-associated viral particles. The effect of heavy and light avian adenovirus-associated viral (A-AV) particles on the replication of several adenovirus serotypes was studied in chicken embryo kidney cells. There was a significant decrease (P less than 0.05) in the number and size of adenovirus-induced plaques at A-AV multiplicities of infection greater than 40. Enhancement of plaque production was observed when A-AV multiplicities of infection were 1 to 40. There was a significant increase in the number and size of infective centers. Analysis of cellular yields indicated an increase in the number of adenoviruses produced per cell. Heavy A-AV particles of buoyant density 1.42 g/cm3 in CsCl were found to enhance plaque production more than light particles (1.38 g/cm3). Conversely, light particles showed greater inhibition of plaque production. Adenovirus serotypes varied in their response to enhancement or inhibition by A-AV particles of different density."}
{"id": "PMID:229749", "title": "Effects of Sendai virus infection on function of cultured mouse alveolar macrophages.", "content": "Cultured mouse alveolar macrophages supported the growth of Sendai virus (murine parainfluenza I virus), as measured by both a 10-fold increase in extracellular virus titers and development of viral antigens on most of the cells. Synthesis of virus continued for at least 1 month without cytopathic effects. Macrophage phagocytic activity for Candida, Staphylococcus epidermidis, and opsonized erythrocytes remained unaffected by the infection, and the ability of the cells to kill S. epidermidis and S. Aureus was also unchanged. The defects in alveolar macrophage function observed in Sendai-infected mouse lungs probably are not due to a direct effect of the virus on macrophage function.", "contents": "Effects of Sendai virus infection on function of cultured mouse alveolar macrophages. Cultured mouse alveolar macrophages supported the growth of Sendai virus (murine parainfluenza I virus), as measured by both a 10-fold increase in extracellular virus titers and development of viral antigens on most of the cells. Synthesis of virus continued for at least 1 month without cytopathic effects. Macrophage phagocytic activity for Candida, Staphylococcus epidermidis, and opsonized erythrocytes remained unaffected by the infection, and the ability of the cells to kill S. epidermidis and S. Aureus was also unchanged. The defects in alveolar macrophage function observed in Sendai-infected mouse lungs probably are not due to a direct effect of the virus on macrophage function."}
{"id": "PMID:229750", "title": "Peripheral vascular disease following radiation therapy.", "content": "Radiation therapy is effective for the treatment of many malignant diseases. This fact is well documented. The existence of complications in any treatment form does not obviate its usefulness. An awareness of possible complications, however, makes our treatment program more realistic and causes us to be more aware of the patient's complaints following therapy. One of our patients complained of claudication for seven years before an arteriogram was done. How many swollen, painful arms after mastectomy and irradiation have been passed off as due to lymphedema or a complaining patient? Exertional chest pain in a young person after mediastinal irradiation should not be overlooked. These symptomatic lesions are amenable to surgical correction. Great care must be spent when incising irradiated skin areas. The use of Silastic sheeting may be useful in extreme cases of radiation fibrosis involving the ureter. While no human studies are available for documentation, based on animal studies, it may be useful to decrease lipidemic situations through dietary prudence during radiation therapy. Finally, we are reminded again that many of our therapeutic triumphs are tarnished with serious side effects.", "contents": "Peripheral vascular disease following radiation therapy. Radiation therapy is effective for the treatment of many malignant diseases. This fact is well documented. The existence of complications in any treatment form does not obviate its usefulness. An awareness of possible complications, however, makes our treatment program more realistic and causes us to be more aware of the patient's complaints following therapy. One of our patients complained of claudication for seven years before an arteriogram was done. How many swollen, painful arms after mastectomy and irradiation have been passed off as due to lymphedema or a complaining patient? Exertional chest pain in a young person after mediastinal irradiation should not be overlooked. These symptomatic lesions are amenable to surgical correction. Great care must be spent when incising irradiated skin areas. The use of Silastic sheeting may be useful in extreme cases of radiation fibrosis involving the ureter. While no human studies are available for documentation, based on animal studies, it may be useful to decrease lipidemic situations through dietary prudence during radiation therapy. Finally, we are reminded again that many of our therapeutic triumphs are tarnished with serious side effects."}
{"id": "PMID:229751", "title": "Changing patterns of breast cancer.", "content": "Changes in treatment of breast cancer are high-lighted as follows: 1) Outpatient breast biopsy offers advantages in planning treatment and also saves money, 2) Mammograms are increasing the numbers of breast tumors found early, 3) For many reasons modified mastectomy is finding increasing use, 4) Breast cancer appears to be multifocal at least one-half of the time. Multifocal breast cancer is more aggressive, 5) Bilateral breast cancer appears to have a very favorable prognosis, especially when non-simultaneous.", "contents": "Changing patterns of breast cancer. Changes in treatment of breast cancer are high-lighted as follows: 1) Outpatient breast biopsy offers advantages in planning treatment and also saves money, 2) Mammograms are increasing the numbers of breast tumors found early, 3) For many reasons modified mastectomy is finding increasing use, 4) Breast cancer appears to be multifocal at least one-half of the time. Multifocal breast cancer is more aggressive, 5) Bilateral breast cancer appears to have a very favorable prognosis, especially when non-simultaneous."}
{"id": "PMID:229752", "title": "Plasma and urine cyclic guanosine 3':5'-monophosphate in disseminated cancer.", "content": "Plasma and 24-h urinary adenosine 3':5'-monophosphate (cyclic AMP) and guanosine 3':5'-monophosphate (cyclic GMP) were measured by radioimmunoassay in 12 normal subjects, 33 patients with six types of non-neoplastic disease (cholelithiasis, peptic ulcer, coronary heart disease, hypertension, regional ileitis, and cirrhosis), and 34 patients with five types of disseminated neoplastic disease (acute myelocytic leukemia; Hodgkin's disease; and metastatic cancer of the lung, colon, and breast). In patients with non-neoplastic disease, cyclic nucleotide values in plasma and urine did not differ significantly (P greater than 0.05) from those in normal subjects. In patients with disseminated cancer, cyclic AMP values in plasma and urine likewise did not differ significantly from those in normal subjects. Plasma cyclic GMP, in contrast, was significantly elevated in all five types of cancer patients, and urinary cyclic GMP was significantly elevated (five times the normal mean) in patients with acute myelogenous leukemia and Hodgkin's disease.", "contents": "Plasma and urine cyclic guanosine 3':5'-monophosphate in disseminated cancer. Plasma and 24-h urinary adenosine 3':5'-monophosphate (cyclic AMP) and guanosine 3':5'-monophosphate (cyclic GMP) were measured by radioimmunoassay in 12 normal subjects, 33 patients with six types of non-neoplastic disease (cholelithiasis, peptic ulcer, coronary heart disease, hypertension, regional ileitis, and cirrhosis), and 34 patients with five types of disseminated neoplastic disease (acute myelocytic leukemia; Hodgkin's disease; and metastatic cancer of the lung, colon, and breast). In patients with non-neoplastic disease, cyclic nucleotide values in plasma and urine did not differ significantly (P greater than 0.05) from those in normal subjects. In patients with disseminated cancer, cyclic AMP values in plasma and urine likewise did not differ significantly from those in normal subjects. Plasma cyclic GMP, in contrast, was significantly elevated in all five types of cancer patients, and urinary cyclic GMP was significantly elevated (five times the normal mean) in patients with acute myelogenous leukemia and Hodgkin's disease."}
{"id": "PMID:229754", "title": "Small cell undifferentiated carcinoma of the larynx.", "content": "A patient with a small cell, undifferentiated carcinoma of the larynx is described. The tumor appeared to arise in close association with subglottic minor salivary glands. Ultrastructural study of the tumor cells showed neurosecretory granules similar to those seen in normal Kulchitsky cells and pulmonary oat cell carcinomas. Bronchogenic oat cell carcinoma and small cell undifferentiated carcinoma of minor salivary gland tissue probably originate from the same cell type. The aggressive behavior of this tumor suggests the need for early systemic treatment including combination chemotherpay.", "contents": "Small cell undifferentiated carcinoma of the larynx. A patient with a small cell, undifferentiated carcinoma of the larynx is described. The tumor appeared to arise in close association with subglottic minor salivary glands. Ultrastructural study of the tumor cells showed neurosecretory granules similar to those seen in normal Kulchitsky cells and pulmonary oat cell carcinomas. Bronchogenic oat cell carcinoma and small cell undifferentiated carcinoma of minor salivary gland tissue probably originate from the same cell type. The aggressive behavior of this tumor suggests the need for early systemic treatment including combination chemotherpay."}
{"id": "PMID:229758", "title": "Cyclic adenosine 3', 5' monophosphate: a possible indicator of premalignant changes in the large bowel.", "content": "Cyclic adenosine 3', 5' monophosphate (cyclic-AMP) has been estimated in mucosal biopsy samples removed from the descending colon and rectum at endoscopy to investigate the possibility of using this substance for monitoring pre-malignant changes in the large bowel. Four groups of patients have been studied: those with normal large bowel and rectal mucosa; those with non-malignant inflammatory bowel disease; those with an adenomatous polyp in the descending colon or sigmoid colon; and those with a rectal adenocarcinoma. No difference was found in the cyclic-AMP content of 'normal' rectal mucosa, 'normal' colonic mucosa, 'diseased' colonic mucosa, carcinomas, and uninvolved mucosa adjacent to the polyps. Less cyclic-AMP was found in the polyps than in adjacent uninvolved mucosa. Conversely, more cyclic-AMP was found in the carcinomas than in adjacent uninvolved mucosa. It is concluded that although cyclic-AMP may be a very useful parameter for delineating the extent of the disease in individual patients, it is not a suitable biochemical marker for the screening of neoplastic changes in the large bowel in the population as a whole.", "contents": "Cyclic adenosine 3', 5' monophosphate: a possible indicator of premalignant changes in the large bowel. Cyclic adenosine 3', 5' monophosphate (cyclic-AMP) has been estimated in mucosal biopsy samples removed from the descending colon and rectum at endoscopy to investigate the possibility of using this substance for monitoring pre-malignant changes in the large bowel. Four groups of patients have been studied: those with normal large bowel and rectal mucosa; those with non-malignant inflammatory bowel disease; those with an adenomatous polyp in the descending colon or sigmoid colon; and those with a rectal adenocarcinoma. No difference was found in the cyclic-AMP content of 'normal' rectal mucosa, 'normal' colonic mucosa, 'diseased' colonic mucosa, carcinomas, and uninvolved mucosa adjacent to the polyps. Less cyclic-AMP was found in the polyps than in adjacent uninvolved mucosa. Conversely, more cyclic-AMP was found in the carcinomas than in adjacent uninvolved mucosa. It is concluded that although cyclic-AMP may be a very useful parameter for delineating the extent of the disease in individual patients, it is not a suitable biochemical marker for the screening of neoplastic changes in the large bowel in the population as a whole."}
{"id": "PMID:229759", "title": "Specific methods for the determination of radioactivity in D-(-)-3-hydroxybutyrate in blood plasma.", "content": "Two simple, high-yield rapid methods with good reproducibility are described, which permit the determination of radioactivity in plasma D-(-)-3-hydroxybutyrate. The compound is converted to acetoacetate, using a modified enzymatic method. In procedure 1, acetoacetate is reacted with 2,4-dinitrophenylhydrazine; the resulting hydrazone is oxidised by means of a sample oxidiser, and the product 14CO2 is collected in scintillation liquid and counted. In procedure 2, a Conway microdiffusion unit is applied. The acetoacetate is decarboxylated to acetone in the presence of o-phenylenediamine, and the acetone is then diffused into semicarbazide solution. This solution, containing the semicarbazone derivative of labelled acetone, is transferred to liquid scintillation and counted. In both procedures the radioactivity is measured simultaneously in a separate sample which was not subjected to the enzymatic conversion of D-(-)-3-hydroxybutyrate. The difference in radioactivity between the two samples is attributed to labelled (D-(-)-3-hydroxybutyrate.", "contents": "Specific methods for the determination of radioactivity in D-(-)-3-hydroxybutyrate in blood plasma. Two simple, high-yield rapid methods with good reproducibility are described, which permit the determination of radioactivity in plasma D-(-)-3-hydroxybutyrate. The compound is converted to acetoacetate, using a modified enzymatic method. In procedure 1, acetoacetate is reacted with 2,4-dinitrophenylhydrazine; the resulting hydrazone is oxidised by means of a sample oxidiser, and the product 14CO2 is collected in scintillation liquid and counted. In procedure 2, a Conway microdiffusion unit is applied. The acetoacetate is decarboxylated to acetone in the presence of o-phenylenediamine, and the acetone is then diffused into semicarbazide solution. This solution, containing the semicarbazone derivative of labelled acetone, is transferred to liquid scintillation and counted. In both procedures the radioactivity is measured simultaneously in a separate sample which was not subjected to the enzymatic conversion of D-(-)-3-hydroxybutyrate. The difference in radioactivity between the two samples is attributed to labelled (D-(-)-3-hydroxybutyrate."}
{"id": "PMID:229760", "title": "Enzyme immunoassay: a review.", "content": "In the last few years, the use of enzyme labels in immunoassays has been investigated. The aim of this review is to evaluate critically the role of such labels in clinical biochemistry. Special attention has been given to the problems involved in preparing enzyme labels and the ways in which such labels can be used in a variety of heterogeneous and homogeneous assay systems.", "contents": "Enzyme immunoassay: a review. In the last few years, the use of enzyme labels in immunoassays has been investigated. The aim of this review is to evaluate critically the role of such labels in clinical biochemistry. Special attention has been given to the problems involved in preparing enzyme labels and the ways in which such labels can be used in a variety of heterogeneous and homogeneous assay systems."}
{"id": "PMID:229766", "title": "Bioaccumulation and depuration of enteroviruses by the soft-shelled clam, Mya arenaria.", "content": "Low levels of feces-associated natural virus, simulating virus numbers estimated to exist in moderately polluted shellfish-growing waters, were used to evaluate the effectiveness of depuration as a virus depletion procedure in soft-shell clams. Depuration effectiveness depended upon the numbers of virus bioaccumulated and whether virus was solids associated. Virus uptake was greatest when viruses were solids associated and pollution levels were equivalent or greater than those likely to be found in grossly polluted growing waters. Virtually all bioaccumulated feces-associated natural virus was deposited within either the hepatopancreas or siphon tissues. Viruses usually were eliminated within a 24- to 48-h depuration period. Dependence upon depuration of clams to elimate health hazards of virus etiology involved a risk factor not measureable in the study. The greatest reduction of health risks would come from the routine depuration of clams harvested from growing waters of good sanitary quality.", "contents": "Bioaccumulation and depuration of enteroviruses by the soft-shelled clam, Mya arenaria. Low levels of feces-associated natural virus, simulating virus numbers estimated to exist in moderately polluted shellfish-growing waters, were used to evaluate the effectiveness of depuration as a virus depletion procedure in soft-shell clams. Depuration effectiveness depended upon the numbers of virus bioaccumulated and whether virus was solids associated. Virus uptake was greatest when viruses were solids associated and pollution levels were equivalent or greater than those likely to be found in grossly polluted growing waters. Virtually all bioaccumulated feces-associated natural virus was deposited within either the hepatopancreas or siphon tissues. Viruses usually were eliminated within a 24- to 48-h depuration period. Dependence upon depuration of clams to elimate health hazards of virus etiology involved a risk factor not measureable in the study. The greatest reduction of health risks would come from the routine depuration of clams harvested from growing waters of good sanitary quality."}
{"id": "PMID:229762", "title": "Classification of tumors of testis.", "content": "In adult patients, testicular tumors consist predominantly of seminoma, embryonal carcinoma, teratoma, choriocarcinoma and mixtures of these. In infants and children, yolk sac tumor and teratoma are the usual tumors; in older age patients, it is predominantly spermatocytic seminoma and malignant lymphoma, although the others may occur as well. Leydig and Sertoli-granulosa cell tumors occur in all ages. The introduction of tumor markers and the capability to demonstrate these in tissue are the most important recent developments. However, there is great need for correlation of histology with these markers and histological demonstration of them.", "contents": "Classification of tumors of testis. In adult patients, testicular tumors consist predominantly of seminoma, embryonal carcinoma, teratoma, choriocarcinoma and mixtures of these. In infants and children, yolk sac tumor and teratoma are the usual tumors; in older age patients, it is predominantly spermatocytic seminoma and malignant lymphoma, although the others may occur as well. Leydig and Sertoli-granulosa cell tumors occur in all ages. The introduction of tumor markers and the capability to demonstrate these in tissue are the most important recent developments. However, there is great need for correlation of histology with these markers and histological demonstration of them."}
{"id": "PMID:229767", "title": "Survey of human enterovirus occurrence in fresh and marine surface waters on Long Island.", "content": "A variety of surface water systems, including a lake, a creek, and two marine embayments, were analyzed on a monthly basis for indigenous human enteroviruses and coliform bacteria. Findings are discussed in terms of the probable pollution sources to each system and their relationship to data from previous studies.", "contents": "Survey of human enterovirus occurrence in fresh and marine surface waters on Long Island. A variety of surface water systems, including a lake, a creek, and two marine embayments, were analyzed on a monthly basis for indigenous human enteroviruses and coliform bacteria. Findings are discussed in terms of the probable pollution sources to each system and their relationship to data from previous studies."}
{"id": "PMID:229763", "title": "Assessment of cellular immune response to cancer of the breast.", "content": "Cellular immune competence and cell-mediated immunity to tumor antigens have been studied in patients with breast cancer. Some patients have been shown to have depressed lymphoproliferative responses to phytohemagglutinin and in mixed leukocyte culture. In some cases, this depression appeared attributable to suppressor cells. Many patients with breast cancer had a cellular immunity to extracts of autologous or allogenetic tumors, as detected by lymphoproliferation and leukocyte migration inhibition assays. In addition, some breast cancer patients reacted to antigens associated with murine mammary tumor virus. Some of the tests for cellular immunity have revealed correlations with clinical course and, therefore, may be of use in the management of patients with breast cancer.", "contents": "Assessment of cellular immune response to cancer of the breast. Cellular immune competence and cell-mediated immunity to tumor antigens have been studied in patients with breast cancer. Some patients have been shown to have depressed lymphoproliferative responses to phytohemagglutinin and in mixed leukocyte culture. In some cases, this depression appeared attributable to suppressor cells. Many patients with breast cancer had a cellular immunity to extracts of autologous or allogenetic tumors, as detected by lymphoproliferation and leukocyte migration inhibition assays. In addition, some breast cancer patients reacted to antigens associated with murine mammary tumor virus. Some of the tests for cellular immunity have revealed correlations with clinical course and, therefore, may be of use in the management of patients with breast cancer."}
{"id": "PMID:229768", "title": "Mode of initiation of cell infection with sludge-associated poliovirus.", "content": "Association with sludge solids did not allow poliovirus to enter cells other than through the normal receptor-mediated route. This implies that the infectivities of sludge-encapsulated virions are masked until their exposure permits binding to cell surface receptors.", "contents": "Mode of initiation of cell infection with sludge-associated poliovirus. Association with sludge solids did not allow poliovirus to enter cells other than through the normal receptor-mediated route. This implies that the infectivities of sludge-encapsulated virions are masked until their exposure permits binding to cell surface receptors."}
{"id": "PMID:229774", "title": "Familial hypobetalipoproteinaemia in 9 children diagnosed as the result of cord blood screening for hypolipoproteinaemia in 10 000 Danish newborns.", "content": "Out of 10 440 children, 266 with low (less than 2.5 centile) values for very low-low density lipoproteins in cord serum were chosen to be followed up to find out how many came from families with familial hypobetalipoproteinaemia (FHBL). In 176 families (66% of 266 families), FHBL was diagnosed in 9 children and their families.", "contents": "Familial hypobetalipoproteinaemia in 9 children diagnosed as the result of cord blood screening for hypolipoproteinaemia in 10 000 Danish newborns. Out of 10 440 children, 266 with low (less than 2.5 centile) values for very low-low density lipoproteins in cord serum were chosen to be followed up to find out how many came from families with familial hypobetalipoproteinaemia (FHBL). In 176 families (66% of 266 families), FHBL was diagnosed in 9 children and their families."}
{"id": "PMID:229777", "title": "Fate of herpes simplex virus in lymphocytes from inflammatory joint effusions. i. Failure of the virus to grow in cultured lymphocytes.", "content": "The ability of lymphocytes isolated from the blood and synovial effusions of patients with rheumatoid arthritis to support the growth of herpex simplex virus (HSV) was studied. Whereas blood lymphocytes supported virus growth, effusion lymphocytes were usually non-permissive. Lymphocytes obtained from the effusions of patients with other forms of inflammatory arthritis or suspected viral arthritis commonly failed to support the growth of HSV, but the virus grew in effusion lymphocytes from patients with noninflammatory joint disease. Several nonspecific factors which might have accounted for this non-permissiveness were excluded.", "contents": "Fate of herpes simplex virus in lymphocytes from inflammatory joint effusions. i. Failure of the virus to grow in cultured lymphocytes. The ability of lymphocytes isolated from the blood and synovial effusions of patients with rheumatoid arthritis to support the growth of herpex simplex virus (HSV) was studied. Whereas blood lymphocytes supported virus growth, effusion lymphocytes were usually non-permissive. Lymphocytes obtained from the effusions of patients with other forms of inflammatory arthritis or suspected viral arthritis commonly failed to support the growth of HSV, but the virus grew in effusion lymphocytes from patients with noninflammatory joint disease. Several nonspecific factors which might have accounted for this non-permissiveness were excluded."}
{"id": "PMID:229775", "title": "Early changes in the chemical composition of the rat lung after silica administration.", "content": "A group of 200 g male Sprague-Dawley rats was injected with 75 mg of quartz (less than 5 mu particle size) and changes in lung DNA, noncollagenous protein, total lipids, and collagen were studied after 6, 24, 72, 96, and 144 hr. Another group of rats received 10, 30, 59, and 75 mg quartz and the above lung analysis was performed 6 days later. Control rats received saline only. Both sets of experiments indicate that striking changes in the above parameters occur very early. The sequence of statistically significant changes was: lung weight (24 hr), DNA (24 hr), noncollagenous proteins (72 hr), total lipids (72 hr), collagen (144 hr). At the dose of 30 mg quartz/lung all the above parameters were significantly increased within 6 days after the lung injury. It is proposed that in early stages of experimental silicosis an excessive amount of collagen accumulates in the lung. Later, some of the deposited collagen is resorbed. This indicates that in the course of the silicotic fibroproliferative inflammation, the balance between collagen deposition and degradation varies.", "contents": "Early changes in the chemical composition of the rat lung after silica administration. A group of 200 g male Sprague-Dawley rats was injected with 75 mg of quartz (less than 5 mu particle size) and changes in lung DNA, noncollagenous protein, total lipids, and collagen were studied after 6, 24, 72, 96, and 144 hr. Another group of rats received 10, 30, 59, and 75 mg quartz and the above lung analysis was performed 6 days later. Control rats received saline only. Both sets of experiments indicate that striking changes in the above parameters occur very early. The sequence of statistically significant changes was: lung weight (24 hr), DNA (24 hr), noncollagenous proteins (72 hr), total lipids (72 hr), collagen (144 hr). At the dose of 30 mg quartz/lung all the above parameters were significantly increased within 6 days after the lung injury. It is proposed that in early stages of experimental silicosis an excessive amount of collagen accumulates in the lung. Later, some of the deposited collagen is resorbed. This indicates that in the course of the silicotic fibroproliferative inflammation, the balance between collagen deposition and degradation varies."}
{"id": "PMID:229778", "title": "Fate of herpes simplex virus in lymphocytes from inflammatory joint effusions. ii. Mechanisms of non-permissiveness.", "content": "Mononuclear cells which were isolated from rheumatoid synovial effusions and cultured without prior separation failed to support the growth of herpes simplex virus (HSV). However, subpopulations of T lymphocytes separated on the basis of cell size or receptors for sheep red cells were, in isolation, permissive for this virus. Virus growth in these permissive cells was blocked by cocultivation with the remaining mononuclear cell populations.", "contents": "Fate of herpes simplex virus in lymphocytes from inflammatory joint effusions. ii. Mechanisms of non-permissiveness. Mononuclear cells which were isolated from rheumatoid synovial effusions and cultured without prior separation failed to support the growth of herpes simplex virus (HSV). However, subpopulations of T lymphocytes separated on the basis of cell size or receptors for sheep red cells were, in isolation, permissive for this virus. Virus growth in these permissive cells was blocked by cocultivation with the remaining mononuclear cell populations."}
{"id": "PMID:229776", "title": "Lead-cadmium interaction: effects on viral-induced mortality and tissue residues in mice.", "content": "Simultaneous exposure to lead and cadmium is highly probable due to common environmental sources of exposure. Mice were exposed simultaneously for 10 wek to lead and cadmium and effects were observed on accumulation of the metals in tissues and susceptibility to viral challenge. The incidence of viral-induced mortality was enhanced in all groups of mice exposed to lead and suppressed in groups of mice treated with cadmium. Mice exposed to both lead and cadmium had mortality rates intermediate to those observed after exposure to the individual metals. Lead and cadmium residues in tissues of mice exposed to both metals, as compared to residues in tissues of mice which received lead or cadmium only, indciated that interaction occurs in regard to metabolism, storage, and excretion of these elements. Chronic coexposure to lead and cadmium appears to alter certain effects produced by exposure to each metal alone.", "contents": "Lead-cadmium interaction: effects on viral-induced mortality and tissue residues in mice. Simultaneous exposure to lead and cadmium is highly probable due to common environmental sources of exposure. Mice were exposed simultaneously for 10 wek to lead and cadmium and effects were observed on accumulation of the metals in tissues and susceptibility to viral challenge. The incidence of viral-induced mortality was enhanced in all groups of mice exposed to lead and suppressed in groups of mice treated with cadmium. Mice exposed to both lead and cadmium had mortality rates intermediate to those observed after exposure to the individual metals. Lead and cadmium residues in tissues of mice exposed to both metals, as compared to residues in tissues of mice which received lead or cadmium only, indciated that interaction occurs in regard to metabolism, storage, and excretion of these elements. Chronic coexposure to lead and cadmium appears to alter certain effects produced by exposure to each metal alone."}
{"id": "PMID:229779", "title": "Search for viral nucleic sequences in rheumatoid cells.", "content": "DNA and RNA were extracted from synovial membranes, synovial fibroblast cells, peripheral blood lymphocytes, and synovial fibroblast cells strains derived from patients with rheumatoid arthritis and other joint conditions. They were hybridised after immobilisation on nitrocellulose filters with iodinated viral nucleic acids extracted from measles, rubella virus, SV--40, and a retrovirus, RD--114. In addition, in situ-hybridisation was carried out on sections of synovial membranes by means of iodinated measles and rubella virus RNA. In no case did any hybridisation occur. Positive control systems included synovial fibroblast strains transformed with SV--40, LLC--MK2 cells chronically infected with rubella virus and RD cells infected with RD--114. It was concluded tht the synovial cells did not contain viral genomes of measles, rubella virus, SV--40, or RD--114, or at least at a level equivalent to the positive control cells.", "contents": "Search for viral nucleic sequences in rheumatoid cells. DNA and RNA were extracted from synovial membranes, synovial fibroblast cells, peripheral blood lymphocytes, and synovial fibroblast cells strains derived from patients with rheumatoid arthritis and other joint conditions. They were hybridised after immobilisation on nitrocellulose filters with iodinated viral nucleic acids extracted from measles, rubella virus, SV--40, and a retrovirus, RD--114. In addition, in situ-hybridisation was carried out on sections of synovial membranes by means of iodinated measles and rubella virus RNA. In no case did any hybridisation occur. Positive control systems included synovial fibroblast strains transformed with SV--40, LLC--MK2 cells chronically infected with rubella virus and RD cells infected with RD--114. It was concluded tht the synovial cells did not contain viral genomes of measles, rubella virus, SV--40, or RD--114, or at least at a level equivalent to the positive control cells."}
{"id": "PMID:229780", "title": "Reversal of protein-energy malnutrition in children during treatment of advanced neoplastic disease.", "content": "The effectiveness of enteral and parenteral feeding in supporting a satisfactory nutritional status and/or reversing protein-energy malnutrition was evaluated in 28 children, ages 1-19 (14 female) with advanced malignant disease (21 solid tumors, 7 leukemia-lymphoma). At the onset of treatment, 21 patients received intensive nutritional counseling (INC) and oral supplementation while seven received total parenteral nutrition (TPN). Sixteen of 21 patients who received INC had a decreased intake (x 48 +/- 24%) Recommended Dietary Allowances (RDA) for kilocalories and dramatic weight loss (x 16.4 +/- 12.4%). A total of 18 patients received TPN for a mean of 24 days (7-60); kcal averaged 90 +/- 26% RDA during weight gain. At onset of TPN, the mean serum albumin, transferrin and total lymphocyte counts were 3.06 +/- 0.38 g/dl, 175 +/- 62 mg/dl, and 1102 +/- 966/mm3 respectively, 15/18 children had subnormal anthropometric measurements and 17/18 patients were anergic to recall skin test antigens. TPN for less than 9-14 days neither repleted weight, skinfold reserves, nor serum albumin concentrations (greater than 3.2 g/dl) although an early increase (p less than .02) in transferrin concentration was observed. However, TPN for 28 days supported weight gain (3.27 kg, 16 +/- 6%), increased serum albumin (0.62 +/- 0.43 g/dl, p less than .001) and transferrin (62 +/- 42, p less than .002) to normal concentrations and reversed anergy in 7/11 patients retested. This study documents the severity of protein energy malnutrition which accompanies intense treatment of children with cancer and the nutritional and immunological benefits of a 28 day course of TPN.", "contents": "Reversal of protein-energy malnutrition in children during treatment of advanced neoplastic disease. The effectiveness of enteral and parenteral feeding in supporting a satisfactory nutritional status and/or reversing protein-energy malnutrition was evaluated in 28 children, ages 1-19 (14 female) with advanced malignant disease (21 solid tumors, 7 leukemia-lymphoma). At the onset of treatment, 21 patients received intensive nutritional counseling (INC) and oral supplementation while seven received total parenteral nutrition (TPN). Sixteen of 21 patients who received INC had a decreased intake (x 48 +/- 24%) Recommended Dietary Allowances (RDA) for kilocalories and dramatic weight loss (x 16.4 +/- 12.4%). A total of 18 patients received TPN for a mean of 24 days (7-60); kcal averaged 90 +/- 26% RDA during weight gain. At onset of TPN, the mean serum albumin, transferrin and total lymphocyte counts were 3.06 +/- 0.38 g/dl, 175 +/- 62 mg/dl, and 1102 +/- 966/mm3 respectively, 15/18 children had subnormal anthropometric measurements and 17/18 patients were anergic to recall skin test antigens. TPN for less than 9-14 days neither repleted weight, skinfold reserves, nor serum albumin concentrations (greater than 3.2 g/dl) although an early increase (p less than .02) in transferrin concentration was observed. However, TPN for 28 days supported weight gain (3.27 kg, 16 +/- 6%), increased serum albumin (0.62 +/- 0.43 g/dl, p less than .001) and transferrin (62 +/- 42, p less than .002) to normal concentrations and reversed anergy in 7/11 patients retested. This study documents the severity of protein energy malnutrition which accompanies intense treatment of children with cancer and the nutritional and immunological benefits of a 28 day course of TPN."}
{"id": "PMID:229781", "title": "Prolactin and Leydig cell responsiveness to LH/hCG in the rat.", "content": "The effects of prolactin and 2-bromo-alpha-ergocryptine (CB-154) on Leydig cell function in intact and hypophysectomized male rats were studied. The conclusions can be summarized as follows: prolactin (1) has a direct stimulatory effect on the number of LH receptors on rat Leydig cells, (2) has no effect on the characteristics of the dose-response curve of isolated Leydig cells (hCG stimulated androgen production) in vitro even after treatment with pharmacological doses in vivo, and (3) acts synergistically with LH to stimulate the quantity of androgen produced by the Leydig cells in response to hCG in vitro and to increase the sensitivity of the hCG-dose-response curve. Treatment of intact rats with CB-154 reduced the quantity of androgen produced by the Leydig cells in vitro after exposure to hCG and decreased LH binding to the same cells by 50%. These results suggest that under normal conditions, endogenous prolactin plays a key role in maintaining the functional integrity of rat Leydig cells.", "contents": "Prolactin and Leydig cell responsiveness to LH/hCG in the rat. The effects of prolactin and 2-bromo-alpha-ergocryptine (CB-154) on Leydig cell function in intact and hypophysectomized male rats were studied. The conclusions can be summarized as follows: prolactin (1) has a direct stimulatory effect on the number of LH receptors on rat Leydig cells, (2) has no effect on the characteristics of the dose-response curve of isolated Leydig cells (hCG stimulated androgen production) in vitro even after treatment with pharmacological doses in vivo, and (3) acts synergistically with LH to stimulate the quantity of androgen produced by the Leydig cells in response to hCG in vitro and to increase the sensitivity of the hCG-dose-response curve. Treatment of intact rats with CB-154 reduced the quantity of androgen produced by the Leydig cells in vitro after exposure to hCG and decreased LH binding to the same cells by 50%. These results suggest that under normal conditions, endogenous prolactin plays a key role in maintaining the functional integrity of rat Leydig cells."}
{"id": "PMID:229782", "title": "Lack of adrenal androgen stimulation by ACTH in extreme hyperprolactinemia.", "content": "Acute and prolonged alpha 1-24 corticotropin stimulation was performed on a treated chromophobe adenoma patient with partial ACTH deficiency and extreme hyperprolactinemia. Cortisol and aldosterone stimulated normally. However, the basal concentrations of androstenedione (A) and dehydroepiandrosterone (DHA) were low, and that of DHA-sulfate (DHAS) was undetectable. Furthermore, A and DHA did not stimulate normally, and DHAS did not stimulate at all. It has been claimed that adrenal androgen production is increased in hyperprolactinemia. However, the inability of prolactin (Prl) to maintain adrenal androgen (AA) secretion, with and without added ACTH, is demonstrated in this patient.", "contents": "Lack of adrenal androgen stimulation by ACTH in extreme hyperprolactinemia. Acute and prolonged alpha 1-24 corticotropin stimulation was performed on a treated chromophobe adenoma patient with partial ACTH deficiency and extreme hyperprolactinemia. Cortisol and aldosterone stimulated normally. However, the basal concentrations of androstenedione (A) and dehydroepiandrosterone (DHA) were low, and that of DHA-sulfate (DHAS) was undetectable. Furthermore, A and DHA did not stimulate normally, and DHAS did not stimulate at all. It has been claimed that adrenal androgen production is increased in hyperprolactinemia. However, the inability of prolactin (Prl) to maintain adrenal androgen (AA) secretion, with and without added ACTH, is demonstrated in this patient."}
{"id": "PMID:229783", "title": "Serum antibody levels as risk factors in the dissemination of herpes zoster.", "content": "Serum antibody levels against varicella-zoster virus (VZV) were examined by immune adherence hemagglutination assay (IAHA), indirect fluorescent antibody (IFA) assay, and complement fixation techniques in 67 immunocompromised patients with localized and disseminated herpes zoster. In the serum obtained initially, undetectable IAHA titers were found in 56.5% of the patients with disseminated zoster compared with 18.2% of those with localized zoster. When serum obtained within the first seven days of illness was analyzed, undetectable IAHA titers and IFA titers of less than 32 were noted in 77.8% of those with disseminated zoster but in only 18.5% of those with localized disease. Peak serum antibody titers in patients with disseminated zoster were eventually equal to or greater than those in localized zoster. The patient groups were comparable in age, underlying disease, and therapy, although Hodgkin's disease was more frequent in patients with disseminated zoster. Thus, the absent IAHA or low IFA levels of circulating antibody early in illness were highly significant risk factors in dissemination of virus in herpes zoster.", "contents": "Serum antibody levels as risk factors in the dissemination of herpes zoster. Serum antibody levels against varicella-zoster virus (VZV) were examined by immune adherence hemagglutination assay (IAHA), indirect fluorescent antibody (IFA) assay, and complement fixation techniques in 67 immunocompromised patients with localized and disseminated herpes zoster. In the serum obtained initially, undetectable IAHA titers were found in 56.5% of the patients with disseminated zoster compared with 18.2% of those with localized zoster. When serum obtained within the first seven days of illness was analyzed, undetectable IAHA titers and IFA titers of less than 32 were noted in 77.8% of those with disseminated zoster but in only 18.5% of those with localized disease. Peak serum antibody titers in patients with disseminated zoster were eventually equal to or greater than those in localized zoster. The patient groups were comparable in age, underlying disease, and therapy, although Hodgkin's disease was more frequent in patients with disseminated zoster. Thus, the absent IAHA or low IFA levels of circulating antibody early in illness were highly significant risk factors in dissemination of virus in herpes zoster."}
{"id": "PMID:229784", "title": "Herpes simplex virus and recurrent laryngeal nerve paralysis. Report of a case and review of the literature.", "content": "A 61-year-old man experienced the abrupt onset of a nonspecific febrile illness followed by the acute development of bilateral vocal cord paralysis. There was no evidence for Guillain-Barr\u00e9 syndrome, multiple sclerosis, brainstem encephalitis, myasthenia gravis, metabolic encephalopathy, poliomyelitis, diphtheria, botulism, tumor, vasculitis, or extrinsic nerve compression. No cause for the fever was ascertained, and the vocal cord paralysis improved sponaneously. Acute and convalescent viral serological studies demonstrated a diagnostic complement-fixation antibody titer rise to herpes simplex virus (HSV) and no rise in titer to influenza A and B, cytomegalovirus, poliomyelitis, or Mycoplasma. This case is similar to several others reported in the literature that suggest a viral neuritis in tenth nerve paralyses in children. The difficulties involved in diagnosing HSV CNS disease before death are discussed, and the medical literature is reviewed for evidence that HSV is the etiological agent in selected cranial neuropathies.", "contents": "Herpes simplex virus and recurrent laryngeal nerve paralysis. Report of a case and review of the literature. A 61-year-old man experienced the abrupt onset of a nonspecific febrile illness followed by the acute development of bilateral vocal cord paralysis. There was no evidence for Guillain-Barr\u00e9 syndrome, multiple sclerosis, brainstem encephalitis, myasthenia gravis, metabolic encephalopathy, poliomyelitis, diphtheria, botulism, tumor, vasculitis, or extrinsic nerve compression. No cause for the fever was ascertained, and the vocal cord paralysis improved sponaneously. Acute and convalescent viral serological studies demonstrated a diagnostic complement-fixation antibody titer rise to herpes simplex virus (HSV) and no rise in titer to influenza A and B, cytomegalovirus, poliomyelitis, or Mycoplasma. This case is similar to several others reported in the literature that suggest a viral neuritis in tenth nerve paralyses in children. The difficulties involved in diagnosing HSV CNS disease before death are discussed, and the medical literature is reviewed for evidence that HSV is the etiological agent in selected cranial neuropathies."}
{"id": "PMID:229785", "title": "Structure-function relationship in hemoproteins: the role of cytochrome c3 in the reduction of colloidal sulfur by sulfate-reducing bacteria.", "content": "Cytochromes c3 of different strains of sulfate-reducing bacteria have been purified and tested for their capacity to reduce colloidal sulfur to hydrogen sulfide. The results are in good agreement with the activities reported for the whole cells. Cytochrome c3 is the sulfur reductase of some strains of sulfate-reducing bacteria such as Desulfovibrio desulfuricans Norway 4 and sulfate-reducing bacterium strain 9974 from which the sulfur reductase activity can be purified with the cytochrome c3. In contrast, Desulfovibrio vulgaris Hildenborough cytochrome c3 is inhibited by the product of the reaction namely hydrogen sulfide. Chloramphenicol has no effect on the sulfur reductase activity of D. desulfuricans Norway 4 when resting cells grown on lactate-sulfate medium are put in the presence of colloidal sulfur. This shows that the sulfur reductase activity is constitutive and corresponds to the fact that colloidal sulfur grown cells do not contain more cytochrome c3 (or another sulfur reductase) than lactate-sulfate-grown cells.", "contents": "Structure-function relationship in hemoproteins: the role of cytochrome c3 in the reduction of colloidal sulfur by sulfate-reducing bacteria. Cytochromes c3 of different strains of sulfate-reducing bacteria have been purified and tested for their capacity to reduce colloidal sulfur to hydrogen sulfide. The results are in good agreement with the activities reported for the whole cells. Cytochrome c3 is the sulfur reductase of some strains of sulfate-reducing bacteria such as Desulfovibrio desulfuricans Norway 4 and sulfate-reducing bacterium strain 9974 from which the sulfur reductase activity can be purified with the cytochrome c3. In contrast, Desulfovibrio vulgaris Hildenborough cytochrome c3 is inhibited by the product of the reaction namely hydrogen sulfide. Chloramphenicol has no effect on the sulfur reductase activity of D. desulfuricans Norway 4 when resting cells grown on lactate-sulfate medium are put in the presence of colloidal sulfur. This shows that the sulfur reductase activity is constitutive and corresponds to the fact that colloidal sulfur grown cells do not contain more cytochrome c3 (or another sulfur reductase) than lactate-sulfate-grown cells."}
{"id": "PMID:229786", "title": "Effect of dithiocarb and dimethyl sulfoxide on irreversible binding of 14C-bromobenzene to rat liver microsomal protein.", "content": "The irreversible binding of [14C]-bromobenzene to rat liver microsomal protein in vitro was inhibited by dithiocarb and DMSO. Dithiocarb suppressed this binding in a time- and concentration-dependent manner (I50 = 4.5 10(-5) M). DMSO reduced the degree of covalent binding by 61% from 5 x 10(-5) M to 8 x 10(-4) M. Dithiocarb was also effective in inhibiting irreversible binding of bromobenzene to liver protein in vivo. Our results are consistent with the hypothesis that dithiocarb exerts its antihepatotoxic efficacy by depressing microsomal mixed-function oxidase activity.", "contents": "Effect of dithiocarb and dimethyl sulfoxide on irreversible binding of 14C-bromobenzene to rat liver microsomal protein. The irreversible binding of [14C]-bromobenzene to rat liver microsomal protein in vitro was inhibited by dithiocarb and DMSO. Dithiocarb suppressed this binding in a time- and concentration-dependent manner (I50 = 4.5 10(-5) M). DMSO reduced the degree of covalent binding by 61% from 5 x 10(-5) M to 8 x 10(-4) M. Dithiocarb was also effective in inhibiting irreversible binding of bromobenzene to liver protein in vivo. Our results are consistent with the hypothesis that dithiocarb exerts its antihepatotoxic efficacy by depressing microsomal mixed-function oxidase activity."}
{"id": "PMID:229787", "title": "Viral interference phenomena induced by foot-and-mouth disease temperature-sensitive mutants in bovine kidney cells.", "content": "Cultures of bovine kidney (BK) cells infected with temperature-sensitive (ts) mutants of foot-and-mouth disease virus (FMDV) were incubated at 38.5 degrees C, a temperature nonpermissive for mutant virus growth and RNA synthesis. The cells were subsequently resistant to viral growth and RNA synthesis when superinfected with wild-type FMDV and with heterologous fowl plague virus. The extent of interference was proportional to the multiplicity of infection of the ts mutant. It increased with time elapsed between infection with mutant and challenge infection, becoming greater than 99 percent after 24 hours. Interference was not proportional to decreased levels of cellular protein synthesis. The interference could be produced in the presence of actinomycin D, and thus was apparently mostly caused by the ts mutant itself rather than by interferon. The interference could not be produced in other less susceptible cell lines. Supernatant fluids from the BK cells infected with ts mutant virus interfered with wild-type FMD viral growth and RNA synthesis in fresh BK cells, and also showed low levels of activity in a vesicular stomatitis virus-plaque reduction assay. The properties of the supernatant fluid-interfering agent resembled to some extent those of an interferon. The ts mutant-mediated interference factor was apparently not able to diffuse into the supernatant fluid.", "contents": "Viral interference phenomena induced by foot-and-mouth disease temperature-sensitive mutants in bovine kidney cells. Cultures of bovine kidney (BK) cells infected with temperature-sensitive (ts) mutants of foot-and-mouth disease virus (FMDV) were incubated at 38.5 degrees C, a temperature nonpermissive for mutant virus growth and RNA synthesis. The cells were subsequently resistant to viral growth and RNA synthesis when superinfected with wild-type FMDV and with heterologous fowl plague virus. The extent of interference was proportional to the multiplicity of infection of the ts mutant. It increased with time elapsed between infection with mutant and challenge infection, becoming greater than 99 percent after 24 hours. Interference was not proportional to decreased levels of cellular protein synthesis. The interference could be produced in the presence of actinomycin D, and thus was apparently mostly caused by the ts mutant itself rather than by interferon. The interference could not be produced in other less susceptible cell lines. Supernatant fluids from the BK cells infected with ts mutant virus interfered with wild-type FMD viral growth and RNA synthesis in fresh BK cells, and also showed low levels of activity in a vesicular stomatitis virus-plaque reduction assay. The properties of the supernatant fluid-interfering agent resembled to some extent those of an interferon. The ts mutant-mediated interference factor was apparently not able to diffuse into the supernatant fluid."}
{"id": "PMID:229788", "title": "Influence of genetic and physiological properties of the host cell on the cytopathic expression of herpes simplex virus.", "content": "Two plaque morphology variants, a cell aggregating variant and a syncytial variant, were isolated from MDBK cells infected with the MP mutant of herpes simplex virus, type 1. The variants differed in the polypeptides produced in infected MDBK cells. The properties of the variants were stable on passage in cells and both variants produced only syncytia in KB and Hep-2 cells. The physiological state of MDBK cells influenced the cytopathological expression of the infecting virus, so that, under certain conditions, each variant could shift from one type of plaque morphology to the other. However, attempts to correlate this plaque morphology shift with a difference in the glycopolypeptides synthesized in the infected cells were unsuccessful.", "contents": "Influence of genetic and physiological properties of the host cell on the cytopathic expression of herpes simplex virus. Two plaque morphology variants, a cell aggregating variant and a syncytial variant, were isolated from MDBK cells infected with the MP mutant of herpes simplex virus, type 1. The variants differed in the polypeptides produced in infected MDBK cells. The properties of the variants were stable on passage in cells and both variants produced only syncytia in KB and Hep-2 cells. The physiological state of MDBK cells influenced the cytopathological expression of the infecting virus, so that, under certain conditions, each variant could shift from one type of plaque morphology to the other. However, attempts to correlate this plaque morphology shift with a difference in the glycopolypeptides synthesized in the infected cells were unsuccessful."}
{"id": "PMID:229789", "title": "Immunogenicity of subviral herpes simplex virus preparations. I. Formation of neutralizing antibodies in different animal species after administration of herpes simplex virus solubilized antigens.", "content": "Production of neutralizing antibodies was followed in guinea pigs, rabbits, hamsters and mice immunized with crude antigen extracts (AM) from human diploid cells infected with herpes simplex virus type 1. The AM induced relatively high levels of neutralizing antibodies in all four species. The antibodies were predominantly complement-requiring and remained so even after administration of repeated AM doses. With the strains used, the antibody response was predominantly type specific and, surprisingly, the type specificity of sera usually increased after administration of repeated doses of AM. Guinea pigs seemed to be the best responsive animal species. They developed the highest levels of antibodies and complement-nonrequiring antibodies were seen in them earlier than in the other animal species. The dose-response experiments carried out in guinea pigs indicated that after a single dose administration the ratio between complement-requiring and complement-nonrequiring antibodies was dependent on the amount of antigen administered. When AM was given without adjuvant less efficient antibody production wws observed than after the administration of the same amount of antigen with adjuvant.", "contents": "Immunogenicity of subviral herpes simplex virus preparations. I. Formation of neutralizing antibodies in different animal species after administration of herpes simplex virus solubilized antigens. Production of neutralizing antibodies was followed in guinea pigs, rabbits, hamsters and mice immunized with crude antigen extracts (AM) from human diploid cells infected with herpes simplex virus type 1. The AM induced relatively high levels of neutralizing antibodies in all four species. The antibodies were predominantly complement-requiring and remained so even after administration of repeated AM doses. With the strains used, the antibody response was predominantly type specific and, surprisingly, the type specificity of sera usually increased after administration of repeated doses of AM. Guinea pigs seemed to be the best responsive animal species. They developed the highest levels of antibodies and complement-nonrequiring antibodies were seen in them earlier than in the other animal species. The dose-response experiments carried out in guinea pigs indicated that after a single dose administration the ratio between complement-requiring and complement-nonrequiring antibodies was dependent on the amount of antigen administered. When AM was given without adjuvant less efficient antibody production wws observed than after the administration of the same amount of antigen with adjuvant."}
{"id": "PMID:229790", "title": "Tryptic peptide analysis of the structural proteins of a temperature-sensitive mutant derived from an HVJ (Sendai virus) carrier culture.", "content": "The individual structural polypeptides of HVJ (haemagglutinating virus of Japan--the Sendai strain of parainfluenza 1 virus) were examined by tryptic peptide analysis. [3H]-methionine-labelled structural proteins of the wild-type virus of HVJ (HVJ-W) and [35S]-methionine-labelled corresponding constituent proteins of a temperature-sensitive (ts) mutant (HVJ-pB) derived from an HVJ carrier culture were compared by ion-exchange chromatography on columns of P-type chromobeads. The tryptic peptides of the individual structural proteins showed characteristic elution profiles. In all the structural proteins tested, the chromatographic elution profiles of both strains generally showed a close resemblance. However, certain minor peaks which were present in one strain but absent in the other strain were detected in the preparations of the P, HN, and F polypeptides. Further, analysis of the NP polypeptide showed that a major peak of one strain appeared at a position in the pH gradient different from a seemingly corresponding major peak of the other strain. In the M protein some possibly homologous minor peaks were found to differ between the two strains.", "contents": "Tryptic peptide analysis of the structural proteins of a temperature-sensitive mutant derived from an HVJ (Sendai virus) carrier culture. The individual structural polypeptides of HVJ (haemagglutinating virus of Japan--the Sendai strain of parainfluenza 1 virus) were examined by tryptic peptide analysis. [3H]-methionine-labelled structural proteins of the wild-type virus of HVJ (HVJ-W) and [35S]-methionine-labelled corresponding constituent proteins of a temperature-sensitive (ts) mutant (HVJ-pB) derived from an HVJ carrier culture were compared by ion-exchange chromatography on columns of P-type chromobeads. The tryptic peptides of the individual structural proteins showed characteristic elution profiles. In all the structural proteins tested, the chromatographic elution profiles of both strains generally showed a close resemblance. However, certain minor peaks which were present in one strain but absent in the other strain were detected in the preparations of the P, HN, and F polypeptides. Further, analysis of the NP polypeptide showed that a major peak of one strain appeared at a position in the pH gradient different from a seemingly corresponding major peak of the other strain. In the M protein some possibly homologous minor peaks were found to differ between the two strains."}
{"id": "PMID:229791", "title": "Assembly of viral structural proteins in cells infected with a temperature-sensitive mutant derived from an HVJ (Sendai virus) carrier culture. Brief report.", "content": "The processing of virus polypeptides synthesized in cells infected with HVJ (haemagglutinating virus of Japan--the Sendai strain of parainfluenza 1 virus) was studied. Maturation of a temperature-sensitive (ts) mutant (HVJ-pB) derived from an HVJ carrier culture was inhibited at 38 degrees C incubation. A considerable amount of viral components were made at the restrictive temperature. They were, with the exception of the polypeptide HN, well preserved without a great loss of their function and successfully incorporated into virus particles released after lowering the incubation temperature. The membrane (M) protein seems to be essential for virus morphogenesis.", "contents": "Assembly of viral structural proteins in cells infected with a temperature-sensitive mutant derived from an HVJ (Sendai virus) carrier culture. Brief report. The processing of virus polypeptides synthesized in cells infected with HVJ (haemagglutinating virus of Japan--the Sendai strain of parainfluenza 1 virus) was studied. Maturation of a temperature-sensitive (ts) mutant (HVJ-pB) derived from an HVJ carrier culture was inhibited at 38 degrees C incubation. A considerable amount of viral components were made at the restrictive temperature. They were, with the exception of the polypeptide HN, well preserved without a great loss of their function and successfully incorporated into virus particles released after lowering the incubation temperature. The membrane (M) protein seems to be essential for virus morphogenesis."}
{"id": "PMID:229792", "title": "Inhibition of foot and mouth disease virus and procapsid synthesis by zinc ions. Brief report.", "content": "Zinc ions inhibit virus production and viral RNA synthesis in FMDV infected-BHK 21 cells. The degree of inhibition depends upon the zinc concentration and the time of addition of the drug. A differential inhibition on virus and procapsids synthesis was observed.", "contents": "Inhibition of foot and mouth disease virus and procapsid synthesis by zinc ions. Brief report. Zinc ions inhibit virus production and viral RNA synthesis in FMDV infected-BHK 21 cells. The degree of inhibition depends upon the zinc concentration and the time of addition of the drug. A differential inhibition on virus and procapsids synthesis was observed."}
{"id": "PMID:229793", "title": "Characterization of the polypeptides synthesized in cells infected with a temperature-sensitive mutant derived from an HVJ (Sendai virus) carrier culture.", "content": "The intracellular synthesis of virus-specific polypeptides in cells infected with the wild-type virus of HVJ (HVJ-W) (haemagglutinating virus of Japan--the Sendai strain of parainfluenza 1 virus) and with a temperature-sensitive (ts) mutant (HVJ-pB) derived from an HVJ carrier culture has been analysed by polyacrylamide gel electrophoresis. At the permissive temperature (32 degrees C), all of the known virus structural polypeptides were identified in cells infected with each strain of virus and in addition to the non-structural polypeptides B and C, another polypeptide at the region with a molecular weight of 26,000 to 27,000 (26 to 27K) could be detected in infected cells. At the non-permissive temperature (38 degrees C), the synthesis of the polypeptide M was markedly restrained in cells infected with HVJ-pB, while other major virus polypeptides were present in approximately comparable amounts to cells infected with the wild-type virus. A non-structural polypeptide with a molecular weight of 105K was dominant in ts mutant infected cells at higher temperatures and disappeared after temperature-shift from 38 degrees to 32 degrees C. The production of the non-structural polypeptides B and 27K was also temperature-sensitive. The molecular weights of the polypeptides B, M and 27K in HVJ-pB infected cells were larger than those of the corresponding polypeptides in HVJ-W infected cells. The synthesis of the M protein in HVJ-prinfected cells started just after lowering the incubation temperature and the newly made M protein was successfully incorporated into virus particles.", "contents": "Characterization of the polypeptides synthesized in cells infected with a temperature-sensitive mutant derived from an HVJ (Sendai virus) carrier culture. The intracellular synthesis of virus-specific polypeptides in cells infected with the wild-type virus of HVJ (HVJ-W) (haemagglutinating virus of Japan--the Sendai strain of parainfluenza 1 virus) and with a temperature-sensitive (ts) mutant (HVJ-pB) derived from an HVJ carrier culture has been analysed by polyacrylamide gel electrophoresis. At the permissive temperature (32 degrees C), all of the known virus structural polypeptides were identified in cells infected with each strain of virus and in addition to the non-structural polypeptides B and C, another polypeptide at the region with a molecular weight of 26,000 to 27,000 (26 to 27K) could be detected in infected cells. At the non-permissive temperature (38 degrees C), the synthesis of the polypeptide M was markedly restrained in cells infected with HVJ-pB, while other major virus polypeptides were present in approximately comparable amounts to cells infected with the wild-type virus. A non-structural polypeptide with a molecular weight of 105K was dominant in ts mutant infected cells at higher temperatures and disappeared after temperature-shift from 38 degrees to 32 degrees C. The production of the non-structural polypeptides B and 27K was also temperature-sensitive. The molecular weights of the polypeptides B, M and 27K in HVJ-pB infected cells were larger than those of the corresponding polypeptides in HVJ-W infected cells. The synthesis of the M protein in HVJ-prinfected cells started just after lowering the incubation temperature and the newly made M protein was successfully incorporated into virus particles."}
{"id": "PMID:229794", "title": "A morphological study of human rotavirus.", "content": "Human rotavirus has a characteristic icosahedral structure which has a honeycomb-like appearance on the surface of the smooth particles and 42 polygonal capsomeres in the rough particles.", "contents": "A morphological study of human rotavirus. Human rotavirus has a characteristic icosahedral structure which has a honeycomb-like appearance on the surface of the smooth particles and 42 polygonal capsomeres in the rough particles."}
{"id": "PMID:229795", "title": "Clones of cells from a human embryo lung: their growth and susceptibility to respiratory viruses.", "content": "Colonies of cells were obtained from human fetal lung tissue and exposed to recently isolated respiratory viruses. There was a considerable variation in the number of rounded cells found in different colonies exposed to rhinovirus types 2 and 9 (RV2 and 9), human coronavirus 229E (HCV), adenovirus type 3 (Ad3) and respiratory syncytial virus (RSV). Smaller colonies had more rounded cells than larger colonies. Clones were established from 9 out of 11 colonies. They varied in their rate of growth and the pattern formed on a plastic surface. They varied also in their virus susceptibility particularly to \"difficult\" rhinoviruses such as RV9 and SF1340. One cell clone (HL1/77 Clone 8), was highly susceptible to all these viruses. All cultures were more sensitive to RSV when maintained in F12K medium than in MEM, whereas there was no difference for rhinoviruses.  Influenza A and B and parainfluenza 3 viruses sometimes produced cytopathic effect, and always produced haemadsorption, but unlike the previous strains could not be passed serially and presumably produced little infectious virus. All clones were rather insusceptible to Ad3; but the virus could be passed, whereas coxsackie virus B3 produced no CPE. Substantial yields of coronavirus and rhinovirus were obtained in gelatin sponge cultures. Two \"very difficult\" respiratory viruses which had just been adapted to tissue culture; namely, HS rhinovirus and JK coronavirus grew in 7 of 9 and in 6 of 9 clones respectively.", "contents": "Clones of cells from a human embryo lung: their growth and susceptibility to respiratory viruses. Colonies of cells were obtained from human fetal lung tissue and exposed to recently isolated respiratory viruses. There was a considerable variation in the number of rounded cells found in different colonies exposed to rhinovirus types 2 and 9 (RV2 and 9), human coronavirus 229E (HCV), adenovirus type 3 (Ad3) and respiratory syncytial virus (RSV). Smaller colonies had more rounded cells than larger colonies. Clones were established from 9 out of 11 colonies. They varied in their rate of growth and the pattern formed on a plastic surface. They varied also in their virus susceptibility particularly to \"difficult\" rhinoviruses such as RV9 and SF1340. One cell clone (HL1/77 Clone 8), was highly susceptible to all these viruses. All cultures were more sensitive to RSV when maintained in F12K medium than in MEM, whereas there was no difference for rhinoviruses.  Influenza A and B and parainfluenza 3 viruses sometimes produced cytopathic effect, and always produced haemadsorption, but unlike the previous strains could not be passed serially and presumably produced little infectious virus. All clones were rather insusceptible to Ad3; but the virus could be passed, whereas coxsackie virus B3 produced no CPE. Substantial yields of coronavirus and rhinovirus were obtained in gelatin sponge cultures. Two \"very difficult\" respiratory viruses which had just been adapted to tissue culture; namely, HS rhinovirus and JK coronavirus grew in 7 of 9 and in 6 of 9 clones respectively."}
{"id": "PMID:229796", "title": "Protection of mice against virulent virus infection by a temperature-sensitive mutant derived from an HVJ (Sendai virus) carrier culture.", "content": "Experimental infection with HVJ (haemagglutinating virus of Japan-the Sendai strain of parainfluenza 1 virus) in mice was studied. Aerosol infection of newborn mice with the wild-type virus (HVJ-W) retarded the development of body weight and killed the animals within a few weeks. Large amounts of virus were isolated from both the lungs and the nasal turbinates of infected mice. In contrast, newborn mice exposed by inhalation to a temperature-sensitive (ts) mutant (HVJ-pB) derived from an HVJ carrier culture showed no clinical signs and grew equally well as mock-infected animals. No infectious virus could be recovered from the lungs although the ts mutant grew to moderate titre in the nasal turbinates. The prior inoculation of newborn mice with the ts mutant virus induced a state of significant resistance to subsequent challenge with the virulent wild-type virus. No replication of challenge virus in both lungs and nasal turbinates could be detected and the animals were protected a lethal infection. It is suggested that an avirulent temperature-sensitive mutant which has lost the capacity to replicate in the lower respiratory tract but is still capable of multiplying in the nasal turbinates may be a promising candidate for use in live vaccines especially against the infectious disease of the lower respiratory tract.", "contents": "Protection of mice against virulent virus infection by a temperature-sensitive mutant derived from an HVJ (Sendai virus) carrier culture. Experimental infection with HVJ (haemagglutinating virus of Japan-the Sendai strain of parainfluenza 1 virus) in mice was studied. Aerosol infection of newborn mice with the wild-type virus (HVJ-W) retarded the development of body weight and killed the animals within a few weeks. Large amounts of virus were isolated from both the lungs and the nasal turbinates of infected mice. In contrast, newborn mice exposed by inhalation to a temperature-sensitive (ts) mutant (HVJ-pB) derived from an HVJ carrier culture showed no clinical signs and grew equally well as mock-infected animals. No infectious virus could be recovered from the lungs although the ts mutant grew to moderate titre in the nasal turbinates. The prior inoculation of newborn mice with the ts mutant virus induced a state of significant resistance to subsequent challenge with the virulent wild-type virus. No replication of challenge virus in both lungs and nasal turbinates could be detected and the animals were protected a lethal infection. It is suggested that an avirulent temperature-sensitive mutant which has lost the capacity to replicate in the lower respiratory tract but is still capable of multiplying in the nasal turbinates may be a promising candidate for use in live vaccines especially against the infectious disease of the lower respiratory tract."}
{"id": "PMID:229797", "title": "Rhinoviruses: kinetics of ultraviolet inactivation and effects of UV and heat on immunogenicity.", "content": "The kinetics of ultraviolet inactivation for two human rhinoviruses and poliovirus were compared. No major differences in the rates of ultraviolet inactivation were detectable. All viral preparations inactivated by ultraviolet irradiation induced neutralizing antibody in guinea pigs. In contrast, when guinea pigs were immunized with a heat inactivated rhinovirus preparation, little or no neutralizing antibody was elicited. Immune electron microscopy of the heated rhinovirus preparations revealed the presence of particles resembling empty capsids. These results suggest that rhinoviruses and enteroviruses are affected in a similar manner when subjected to ultraviolet or heat inactivation.", "contents": "Rhinoviruses: kinetics of ultraviolet inactivation and effects of UV and heat on immunogenicity. The kinetics of ultraviolet inactivation for two human rhinoviruses and poliovirus were compared. No major differences in the rates of ultraviolet inactivation were detectable. All viral preparations inactivated by ultraviolet irradiation induced neutralizing antibody in guinea pigs. In contrast, when guinea pigs were immunized with a heat inactivated rhinovirus preparation, little or no neutralizing antibody was elicited. Immune electron microscopy of the heated rhinovirus preparations revealed the presence of particles resembling empty capsids. These results suggest that rhinoviruses and enteroviruses are affected in a similar manner when subjected to ultraviolet or heat inactivation."}
{"id": "PMID:229798", "title": "Role of envelope proteins of paramyxoviruses in the modification of cell membrane antigens.", "content": "Adsorption of paramyxoviruses to separated membranes of tumor cells produces neoantigens that are immunogenic in syngeneic mice (xenogenization). Thus it became possible to study this process by using modified virus or virus fractions. Membranes with adsorbed viral derivatives produced an immune response which was measured by cytotoxic and complement fixing antibodies and the appearance of autoimmune disease. The effect of viral preparations with reduced F (fusion) protein activity was compared to treatment of membranes with equivalent amounts of active or inactive virus as measured by hemagglutination. Viral preparations without hemolytic activity showed diminished adsorption to membranes and the immune response was reduced. Triton X 100 and desoxycholate extracted from membranes immunogenic material with associated paramyxovirus antigens.", "contents": "Role of envelope proteins of paramyxoviruses in the modification of cell membrane antigens. Adsorption of paramyxoviruses to separated membranes of tumor cells produces neoantigens that are immunogenic in syngeneic mice (xenogenization). Thus it became possible to study this process by using modified virus or virus fractions. Membranes with adsorbed viral derivatives produced an immune response which was measured by cytotoxic and complement fixing antibodies and the appearance of autoimmune disease. The effect of viral preparations with reduced F (fusion) protein activity was compared to treatment of membranes with equivalent amounts of active or inactive virus as measured by hemagglutination. Viral preparations without hemolytic activity showed diminished adsorption to membranes and the immune response was reduced. Triton X 100 and desoxycholate extracted from membranes immunogenic material with associated paramyxovirus antigens."}
{"id": "PMID:229799", "title": "Comparison of cowpox-like viruses isolated from European zoos. Brief report.", "content": "Poxviruses isolated from captive carnivores in Russia (Moscow virus) and elephants in Germany (elephant virus) were very closely-related to cowpox virus. Immunological analysis with absorbed sera separated elephant virus but not cowpox and Moscow virus, whereas polypeptide analysis separated cowpox but not elephant and Moscow virus. A combination of biological tests separated all three. The epidemiological implications are briefly reviewed.", "contents": "Comparison of cowpox-like viruses isolated from European zoos. Brief report. Poxviruses isolated from captive carnivores in Russia (Moscow virus) and elephants in Germany (elephant virus) were very closely-related to cowpox virus. Immunological analysis with absorbed sera separated elephant virus but not cowpox and Moscow virus, whereas polypeptide analysis separated cowpox but not elephant and Moscow virus. A combination of biological tests separated all three. The epidemiological implications are briefly reviewed."}
{"id": "PMID:229800", "title": "Polypeptide patterns of infectious bronchitis virus serotypes fall into two categories. Brief report.", "content": "Molecular weights of six major polypeptides of infectious bronchitis virus (IBV) are: 1. 75,000; 2. 50,000; 3. 45,000; 4. 35,000; 5. 28,000 or 24,000, and 6. 22,000 dalton. According to the mobility of protein 5 the polypeptide patterns of IBV serotypes fall into two main categories.", "contents": "Polypeptide patterns of infectious bronchitis virus serotypes fall into two categories. Brief report. Molecular weights of six major polypeptides of infectious bronchitis virus (IBV) are: 1. 75,000; 2. 50,000; 3. 45,000; 4. 35,000; 5. 28,000 or 24,000, and 6. 22,000 dalton. According to the mobility of protein 5 the polypeptide patterns of IBV serotypes fall into two main categories."}
{"id": "PMID:229801", "title": "Herpes simplex virus DNA polymerase, thymidine kinase and deoxyribonuclease activities in cells infected with wild type, ultraviolet-irradiated and defective virus.", "content": "The DNA polymerase, thymidine kinase and deoxyribonuclease activities were studied in cells infected with wild type (wt), ultraviolet (UV)-irradiated and defective herpes simplex virus type 1. All three enzymatic activities were expressed in cells infected with wt virus. In cells infected with UV-irradiated virus, the thymidine kinase and deoxyribonuclease activities were inhibited and the DNA polymerase activity was markedly suppressed. In cells producing defective virus, there was thymidine kinase activity, but the viral deoxyribonuclease activity was considerably reduced. The DNA polymerase activity was fully expressed in cells producing defective virus at passage level 5, but at passage level 6, the activity of the viral DNA polymerase declined.", "contents": "Herpes simplex virus DNA polymerase, thymidine kinase and deoxyribonuclease activities in cells infected with wild type, ultraviolet-irradiated and defective virus. The DNA polymerase, thymidine kinase and deoxyribonuclease activities were studied in cells infected with wild type (wt), ultraviolet (UV)-irradiated and defective herpes simplex virus type 1. All three enzymatic activities were expressed in cells infected with wt virus. In cells infected with UV-irradiated virus, the thymidine kinase and deoxyribonuclease activities were inhibited and the DNA polymerase activity was markedly suppressed. In cells producing defective virus, there was thymidine kinase activity, but the viral deoxyribonuclease activity was considerably reduced. The DNA polymerase activity was fully expressed in cells producing defective virus at passage level 5, but at passage level 6, the activity of the viral DNA polymerase declined."}
{"id": "PMID:229802", "title": "Effects of antimetabolites on the production of tubular structures in Vero cells infected with herpes simplex virus type 2.", "content": "Treatment of Vero cells infected with herpes simplex virus type 2 with the proper concentrations of hydroxyurea (HU) reduced the production of infectious virus and markedly increased the accumulation of tubular structures in the nuclei when the drug was added within 6 hours after infection. Similar accumulation of tubular structures in the infected nuclei was also observed when infected cells were treated with phosphonoacetic acid at proper concentrations. The release of HU-treated, herpes simplex virus type 2-infected cells from the drug-induced blocking of synthesis of infectious virus resulted in the marked decrease of tubular structures coincidentally with the beginning of production of infectious virus. The data suggest the possibility that the disappearance of tubular structures may be related to the active production of infectious virus.", "contents": "Effects of antimetabolites on the production of tubular structures in Vero cells infected with herpes simplex virus type 2. Treatment of Vero cells infected with herpes simplex virus type 2 with the proper concentrations of hydroxyurea (HU) reduced the production of infectious virus and markedly increased the accumulation of tubular structures in the nuclei when the drug was added within 6 hours after infection. Similar accumulation of tubular structures in the infected nuclei was also observed when infected cells were treated with phosphonoacetic acid at proper concentrations. The release of HU-treated, herpes simplex virus type 2-infected cells from the drug-induced blocking of synthesis of infectious virus resulted in the marked decrease of tubular structures coincidentally with the beginning of production of infectious virus. The data suggest the possibility that the disappearance of tubular structures may be related to the active production of infectious virus."}
{"id": "PMID:229803", "title": "Comparisons of some bluetongue virus isolates by plaque neutralization and relatedness tests.", "content": "Seven North American bluetongue virus isolates, cloned by plaquing, and sera to five of them were reacted in a plaque neutralization test. Using a paired controls system, each virus-serum reaction was studied in terms of the regression of percent neutralization on log serum dilution. Antigen-antibody interaction terms in the analysis of effective dose estimates were used to assess the relatedness of the virus isolates. The degree of cross reactivity formed a spectrum from virtually no evidence of unrelatedness to clear antigenic differences.", "contents": "Comparisons of some bluetongue virus isolates by plaque neutralization and relatedness tests. Seven North American bluetongue virus isolates, cloned by plaquing, and sera to five of them were reacted in a plaque neutralization test. Using a paired controls system, each virus-serum reaction was studied in terms of the regression of percent neutralization on log serum dilution. Antigen-antibody interaction terms in the analysis of effective dose estimates were used to assess the relatedness of the virus isolates. The degree of cross reactivity formed a spectrum from virtually no evidence of unrelatedness to clear antigenic differences."}
{"id": "PMID:229804", "title": "Classification of porcine enteroviruses by antigenic analysis and cytopathic effects in tissue culture: description of 3 new serotypes.", "content": "Porcine enteroviruses isolated in the United Kingdom between 1972 and 1976 were compared with the 8 serotypes previously described and with human coxsackie B virus types 1 to 6 for ability to grow in different cell lines. This allowed the classification of all strains into 3 broad groups according to type of cytopathic effect in IBRS-2 cells and further subdivision on the basis of production of cytopathic effect in BHK 21, HeLa and VERO cells. None of the porcine enterovirus strains was neutralized by antisera to human enteroviruses (Lim Benyesh-Melnick Pools) with the exception of swine vesicular disease virus, which was neutralised by coxsackie B5 antiserum. Antisera prepared either in gnotobiotic pigs or in guinea pigs against the 8 porcine enterovirus serotypes failed to neutralize 9 isolates which could be classified into 3 new serotypes, for which Nos. 9, 10 and 11 are proposed. Guinea pig sera could be used as an alternative to gnotobiotic pig sera for type differentiation.", "contents": "Classification of porcine enteroviruses by antigenic analysis and cytopathic effects in tissue culture: description of 3 new serotypes. Porcine enteroviruses isolated in the United Kingdom between 1972 and 1976 were compared with the 8 serotypes previously described and with human coxsackie B virus types 1 to 6 for ability to grow in different cell lines. This allowed the classification of all strains into 3 broad groups according to type of cytopathic effect in IBRS-2 cells and further subdivision on the basis of production of cytopathic effect in BHK 21, HeLa and VERO cells. None of the porcine enterovirus strains was neutralized by antisera to human enteroviruses (Lim Benyesh-Melnick Pools) with the exception of swine vesicular disease virus, which was neutralised by coxsackie B5 antiserum. Antisera prepared either in gnotobiotic pigs or in guinea pigs against the 8 porcine enterovirus serotypes failed to neutralize 9 isolates which could be classified into 3 new serotypes, for which Nos. 9, 10 and 11 are proposed. Guinea pig sera could be used as an alternative to gnotobiotic pig sera for type differentiation."}
{"id": "PMID:229805", "title": "Production of interferon by human tumor cell lines.", "content": "Fourteen continuous human cell lines, including nine derived from tumors and five from non-neoplastic tissues, produced interferon in response to induction with bluetongue virus (BTV), Newcastle disease virus (NDV), and poly(I) . poly(C) complexed with DEAE-dextran. The seven best interferon-producing cell lines (one from a melanoma, five derived from carcinomas, and one SV40-virus-transformed kidney cell line) responded to at least one of the viral inducers with yields of interferon over 1000 units/ml. Because the HT-1376 bladder carcinoma cell line produced high yields of interferon in this survey, and is easily propagated, the optimal conditions for interferon production were investigated, using BTV as the inducer. Interferon yields in 59 inductions over a period of about two years consistently fell within a 6-fold range, and had a geometric mean titer of about 2700 reference units (RU)/ml, representing the production of about 3 RU/10(3) cells. This yield is comparable to mean titers of 1 to 10 RU/10(3) cells obtained by others with human leukocytes, foreskin cell strains, or the Namalva lymphoblastoid cell line. UV-inactivated BTV at a multiplicity corresponding to 10 PFU/cell was as effective an inducer in the HT-1376 cell line as the fully infectious virus at a multiplicity of 1 PFU/cell. The interferon produced by the HT-1376 epithelial cell line has characteristics similar to the interferon induced by poly(I) . poly(C) in human diploid fibroblasts. These studies clearly demonstrate that many different types of tumor-derived cells have the capacity to produce interferon, and that some equal or surpass the efficiency of diploid cells.", "contents": "Production of interferon by human tumor cell lines. Fourteen continuous human cell lines, including nine derived from tumors and five from non-neoplastic tissues, produced interferon in response to induction with bluetongue virus (BTV), Newcastle disease virus (NDV), and poly(I) . poly(C) complexed with DEAE-dextran. The seven best interferon-producing cell lines (one from a melanoma, five derived from carcinomas, and one SV40-virus-transformed kidney cell line) responded to at least one of the viral inducers with yields of interferon over 1000 units/ml. Because the HT-1376 bladder carcinoma cell line produced high yields of interferon in this survey, and is easily propagated, the optimal conditions for interferon production were investigated, using BTV as the inducer. Interferon yields in 59 inductions over a period of about two years consistently fell within a 6-fold range, and had a geometric mean titer of about 2700 reference units (RU)/ml, representing the production of about 3 RU/10(3) cells. This yield is comparable to mean titers of 1 to 10 RU/10(3) cells obtained by others with human leukocytes, foreskin cell strains, or the Namalva lymphoblastoid cell line. UV-inactivated BTV at a multiplicity corresponding to 10 PFU/cell was as effective an inducer in the HT-1376 cell line as the fully infectious virus at a multiplicity of 1 PFU/cell. The interferon produced by the HT-1376 epithelial cell line has characteristics similar to the interferon induced by poly(I) . poly(C) in human diploid fibroblasts. These studies clearly demonstrate that many different types of tumor-derived cells have the capacity to produce interferon, and that some equal or surpass the efficiency of diploid cells."}
{"id": "PMID:229806", "title": "A new method for the isolation of undegraded FMDV-specific RNA from infected BHK cells.", "content": "Fractionation of Foot-and-Mouth disease virus infected cells by currently described procedures, leads to the appearance of variable amounts of heterogeneous single-stranded RNA fragments. A new method based upon the fractionation of cultured cells at extremely low temperatures has been developed to minimize the degradation of the viral RNAs by cellular nucleases. It was shown that the viral RNAs obtained by this procedure were almost non-degraded, and similar to those found in other picornavirus infected cells. More than 90 per cent of the polysomal RNAs were found as genome-size molecules, presumably being messenger RNA (mRNA). It was also found that the mRNA analyzed on sucrose gradients sedimented slightly ahead of the 35S genomic RNA. However, no differences were found when the analysis was performed on polyacrylamide gels.", "contents": "A new method for the isolation of undegraded FMDV-specific RNA from infected BHK cells. Fractionation of Foot-and-Mouth disease virus infected cells by currently described procedures, leads to the appearance of variable amounts of heterogeneous single-stranded RNA fragments. A new method based upon the fractionation of cultured cells at extremely low temperatures has been developed to minimize the degradation of the viral RNAs by cellular nucleases. It was shown that the viral RNAs obtained by this procedure were almost non-degraded, and similar to those found in other picornavirus infected cells. More than 90 per cent of the polysomal RNAs were found as genome-size molecules, presumably being messenger RNA (mRNA). It was also found that the mRNA analyzed on sucrose gradients sedimented slightly ahead of the 35S genomic RNA. However, no differences were found when the analysis was performed on polyacrylamide gels."}
{"id": "PMID:229807", "title": "Determination of antibodies against cytomegalovirus-induced early antigens by using rabbit lung fibroblasts. Brief report.", "content": "The determination of antibodies against cytomegalovirus-induced antigens in 30 patients with acute cytomegalovirus infection and in 100 healthy control persons, using early antigen preparations of human lung fibroblasts and of rabbit lung fibroblasts, yielded results showing a high degree of agreement. For such investigations, however, the use of rabbit cells proved to be of advantage because the preparation of the early antigens can be carried out without inhibition of the DNA synthesis of the host cells.", "contents": "Determination of antibodies against cytomegalovirus-induced early antigens by using rabbit lung fibroblasts. Brief report. The determination of antibodies against cytomegalovirus-induced antigens in 30 patients with acute cytomegalovirus infection and in 100 healthy control persons, using early antigen preparations of human lung fibroblasts and of rabbit lung fibroblasts, yielded results showing a high degree of agreement. For such investigations, however, the use of rabbit cells proved to be of advantage because the preparation of the early antigens can be carried out without inhibition of the DNA synthesis of the host cells."}
{"id": "PMID:229808", "title": "[Ultrastructure of the human submandibular salivary glands].", "content": "By means of electron microscopy cells in the human submandibular glands were studied. It was demonstrated that in acini two types of glandular cells were present: mucosal and seromucosal. In the latter, secretory granules are descrete with electron opaque cores in most of them. Mucocytes are filled with an electron transparent secrete; secretory granules often confluent and their membranes rupture. The acini are surrounded with myoepithelial cells. Intercalated ducts consist of cells with moderately electron opaque granules. In some granules there are dense bodies excentrically situated. In these cells there occur lipid inclusions. Striated ducts are composed of basal (electron transparent) and high cylindric (light and dark) cells. The cylindrical cells have a large amount of mitochondria, deep folds in their basal plasmolemma protruding into cytoplasma. Most of the cells in these parts contain small apically accumulated secretory granules with a dense matrix and separate larger ones scattered in the cell. It is possible to suggest that some secretory granules of ductal or, perhaps, acinar origin contain hormonal products.", "contents": "[Ultrastructure of the human submandibular salivary glands]. By means of electron microscopy cells in the human submandibular glands were studied. It was demonstrated that in acini two types of glandular cells were present: mucosal and seromucosal. In the latter, secretory granules are descrete with electron opaque cores in most of them. Mucocytes are filled with an electron transparent secrete; secretory granules often confluent and their membranes rupture. The acini are surrounded with myoepithelial cells. Intercalated ducts consist of cells with moderately electron opaque granules. In some granules there are dense bodies excentrically situated. In these cells there occur lipid inclusions. Striated ducts are composed of basal (electron transparent) and high cylindric (light and dark) cells. The cylindrical cells have a large amount of mitochondria, deep folds in their basal plasmolemma protruding into cytoplasma. Most of the cells in these parts contain small apically accumulated secretory granules with a dense matrix and separate larger ones scattered in the cell. It is possible to suggest that some secretory granules of ductal or, perhaps, acinar origin contain hormonal products."}
{"id": "PMID:229810", "title": "[Ultrastructural characteristics of soft tissue rhabdomyosarcomas].", "content": "Seven rhabdomyosarcomas of human soft tissues were studied electron microscopically. Certain ultrastructural features characteristic of tumour rhabdomyoblasts were revealed: atypical fibrillar apparatus, spatially uneven process of myofibrillogenesis, disturbed cyto- and histotypical differentiation ratio and others. These features may be used for electron microscopic diagnosis of rhabdomyosarcomas among soft tissue tumours of low differentiation.", "contents": "[Ultrastructural characteristics of soft tissue rhabdomyosarcomas]. Seven rhabdomyosarcomas of human soft tissues were studied electron microscopically. Certain ultrastructural features characteristic of tumour rhabdomyoblasts were revealed: atypical fibrillar apparatus, spatially uneven process of myofibrillogenesis, disturbed cyto- and histotypical differentiation ratio and others. These features may be used for electron microscopic diagnosis of rhabdomyosarcomas among soft tissue tumours of low differentiation."}
{"id": "PMID:229814", "title": "Cavernous hemangioma of the retina. A four-generation pedigree with neurocutaneous manifestations and an example of bilateral retinal involvement.", "content": "Cavernous hemangioma of the retina is an unusual vascular hamartoma whose coexistence with vascular anomalies of the skin and central nervous system has been recognized recently. A 39-year-old woman, who had an acute palsy of the right third cranial nerve, had a history of seizures, cutaneous vascular anomalies, and a cavernous hemangioma of the retina of the right eye. One of her daughters demonstrated bilateral retinal cavernous hemangiomas, and another daughter, who developed seizures when febrile, displayed cutaneous vascular anomalies. A four-generation pedigree showed a number of cutaneous vascular anomalies, seizures, and stroke-related deaths. The pedigree suggests further support for considering this disorder an authentic oculoneurocutaneous triad.", "contents": "Cavernous hemangioma of the retina. A four-generation pedigree with neurocutaneous manifestations and an example of bilateral retinal involvement. Cavernous hemangioma of the retina is an unusual vascular hamartoma whose coexistence with vascular anomalies of the skin and central nervous system has been recognized recently. A 39-year-old woman, who had an acute palsy of the right third cranial nerve, had a history of seizures, cutaneous vascular anomalies, and a cavernous hemangioma of the retina of the right eye. One of her daughters demonstrated bilateral retinal cavernous hemangiomas, and another daughter, who developed seizures when febrile, displayed cutaneous vascular anomalies. A four-generation pedigree showed a number of cutaneous vascular anomalies, seizures, and stroke-related deaths. The pedigree suggests further support for considering this disorder an authentic oculoneurocutaneous triad."}
{"id": "PMID:229815", "title": "A new intermediate adenovirus type causing conjunctivitis.", "content": "A new adenovirus of intermediate type involved in conjunctivitis has been isolated. The virus is related to adenovirus types 13 and 30 by neutralization and to types 10 and 19 by hemagglutination inhibition. Since 1976 the agent has been causing sporadic cases of conjunctivitis in different parts of The Netherlands. Twenty-three cases have been established by virus isolation from the affected eyes. The symptoms of the disease range from epidemic keratoconjunctivitis to pharyngoconjunctival fever. Also, adenovirus type 13-30/10-19 has been isolated from the cervix uteri of four women in a series of 1,477 women with cervicitis.", "contents": "A new intermediate adenovirus type causing conjunctivitis. A new adenovirus of intermediate type involved in conjunctivitis has been isolated. The virus is related to adenovirus types 13 and 30 by neutralization and to types 10 and 19 by hemagglutination inhibition. Since 1976 the agent has been causing sporadic cases of conjunctivitis in different parts of The Netherlands. Twenty-three cases have been established by virus isolation from the affected eyes. The symptoms of the disease range from epidemic keratoconjunctivitis to pharyngoconjunctival fever. Also, adenovirus type 13-30/10-19 has been isolated from the cervix uteri of four women in a series of 1,477 women with cervicitis."}
{"id": "PMID:229817", "title": "An outbreak of disease in pigeons associated with a herpesvirus.", "content": "An outbreak of disease in young pigeons associated with a herpesvirus is reported. The clinical history, macroscopic and microscopic appearance of lesions and virus isolation are described. Most affected birds showed lesions in the upper alimentary tract epithelium as well as in skin, nasal mucosa and salivary glands. Lesions in liver, spleen and pancreas were uncommon. A herpesvirus capable of producing CPE on tissue culture and lesions on chorioallantoic membrane of developing chicken embryos was isolated and described. Inoculation of experimental pigeons with the virus failed to reproduce the disease.", "contents": "An outbreak of disease in pigeons associated with a herpesvirus. An outbreak of disease in young pigeons associated with a herpesvirus is reported. The clinical history, macroscopic and microscopic appearance of lesions and virus isolation are described. Most affected birds showed lesions in the upper alimentary tract epithelium as well as in skin, nasal mucosa and salivary glands. Lesions in liver, spleen and pancreas were uncommon. A herpesvirus capable of producing CPE on tissue culture and lesions on chorioallantoic membrane of developing chicken embryos was isolated and described. Inoculation of experimental pigeons with the virus failed to reproduce the disease."}
{"id": "PMID:229818", "title": "Somatomedin-like activity, prolactin, growth hormone and insulin in human cord blood.", "content": "In order to assess the possible influence of fetal polypeptide hormones on birth size, somatomedin-like receptor activity (SmLRA) (n = 281), prolactin (n = 158), growth hormone (n = 133) and insulin (n = 108) concentrations were measured in the cord blood of 281 singleton infants born after different complications of pregnancy. Infant sex did not significantly affect the concentration of any hormone. SmLRA concentrations appeared to rise from 25 to 38 weeks of gestation, but thereafter fell. Concentrations of prolactin, growth hormone and insulin correlated negatively with gestational age. Insulin emerged as the hormone most clearly related to fetal growth, since concentrations were high (mean +/- SD = 20.6 +/- 11.5 uU/ml) in serum from infants of diabetic mothers (IDM) and other large-for-dates infants (10.1 +/- 4.8 uU/ml), but low (5.3 +/- 0.5 uU/ml) in infants who were small-for-dates (SFD). In contrast, SmLRA concentrations were high in serum from SFD infants (0.63 +/- 0.29 U/ml) and low in IDM (0.43 +/- 0.16 U/ml). Prolactin concentrations were higher in serum from SFD infants (212 +/- 101 ng/ml) and from IDM (237 +/- 182 ng/ml) than from normal infants born at term (139 +/- 68 ng/ml). Administration of intramuscular betamethasone to pregnant women in premature labour resulted in significant elevations in the concentrations of prolactin and insulin in cord blood.", "contents": "Somatomedin-like activity, prolactin, growth hormone and insulin in human cord blood. In order to assess the possible influence of fetal polypeptide hormones on birth size, somatomedin-like receptor activity (SmLRA) (n = 281), prolactin (n = 158), growth hormone (n = 133) and insulin (n = 108) concentrations were measured in the cord blood of 281 singleton infants born after different complications of pregnancy. Infant sex did not significantly affect the concentration of any hormone. SmLRA concentrations appeared to rise from 25 to 38 weeks of gestation, but thereafter fell. Concentrations of prolactin, growth hormone and insulin correlated negatively with gestational age. Insulin emerged as the hormone most clearly related to fetal growth, since concentrations were high (mean +/- SD = 20.6 +/- 11.5 uU/ml) in serum from infants of diabetic mothers (IDM) and other large-for-dates infants (10.1 +/- 4.8 uU/ml), but low (5.3 +/- 0.5 uU/ml) in infants who were small-for-dates (SFD). In contrast, SmLRA concentrations were high in serum from SFD infants (0.63 +/- 0.29 U/ml) and low in IDM (0.43 +/- 0.16 U/ml). Prolactin concentrations were higher in serum from SFD infants (212 +/- 101 ng/ml) and from IDM (237 +/- 182 ng/ml) than from normal infants born at term (139 +/- 68 ng/ml). Administration of intramuscular betamethasone to pregnant women in premature labour resulted in significant elevations in the concentrations of prolactin and insulin in cord blood."}
{"id": "PMID:229820", "title": "Structural aspects of the dye-linked alcohol dehydrogenase of Rhodopseudomonas acidophila.", "content": "1. A dye-linked alcohol dehydrogenase was purified 60-fold from extracts of Rhodopseudomonas acidophila 10050 grown aerobically on ethanol. 2. The properties of this enzyme were identical with those of the alcohol dehydrogenase synthesized by this organism during growth on methanol anaerobically in the light, and they are judged to be the same enzyme. 3. The enzyme gave a single protein band, coincident with alcohol dehydrogenase activity, during electrophoresis on polyacrylamide gel. 4. The amino acid composition, ioselectric point, u.v. and visible absorption spectra of the enzyme were determined and compared with those of other similar enzymes. 5. The presence of 0.7--1.0 g-atom of non-haem, acidlabile iron/mol of enzyme was shown by atomic absorption spectrophotometry and colorimetric assay. The iron could not be dissociated from the enzyme by dialysis against chelating agents. 6. E.p.r. spectroscopy of the enzyme did not indicate any redox function for the iron during alcohol dehydrogenation, but showed a signal at g = 2.00 consistent with the presence of a protein-bound organic free radical. 8. Antisera were raised against alcohol (methanol) dehydrogenases purified from Rhodopseudomonas acidophila, Paracoccus denitrificans and Methylophilus methylotrophus. 9. The antiserum to the Rhodopseudomonas acidophila enzyme cross-reacted with neither of the two other antisera, nor with crude extracts of methanol-grown Hyphomicrobium X and Pseudomonas AM1, thus emphasizing its singular biochemical properties.", "contents": "Structural aspects of the dye-linked alcohol dehydrogenase of Rhodopseudomonas acidophila. 1. A dye-linked alcohol dehydrogenase was purified 60-fold from extracts of Rhodopseudomonas acidophila 10050 grown aerobically on ethanol. 2. The properties of this enzyme were identical with those of the alcohol dehydrogenase synthesized by this organism during growth on methanol anaerobically in the light, and they are judged to be the same enzyme. 3. The enzyme gave a single protein band, coincident with alcohol dehydrogenase activity, during electrophoresis on polyacrylamide gel. 4. The amino acid composition, ioselectric point, u.v. and visible absorption spectra of the enzyme were determined and compared with those of other similar enzymes. 5. The presence of 0.7--1.0 g-atom of non-haem, acidlabile iron/mol of enzyme was shown by atomic absorption spectrophotometry and colorimetric assay. The iron could not be dissociated from the enzyme by dialysis against chelating agents. 6. E.p.r. spectroscopy of the enzyme did not indicate any redox function for the iron during alcohol dehydrogenation, but showed a signal at g = 2.00 consistent with the presence of a protein-bound organic free radical. 8. Antisera were raised against alcohol (methanol) dehydrogenases purified from Rhodopseudomonas acidophila, Paracoccus denitrificans and Methylophilus methylotrophus. 9. The antiserum to the Rhodopseudomonas acidophila enzyme cross-reacted with neither of the two other antisera, nor with crude extracts of methanol-grown Hyphomicrobium X and Pseudomonas AM1, thus emphasizing its singular biochemical properties."}
{"id": "PMID:229821", "title": "Properties of mammalian nuclear-envelope nucleoside triphosphatase.", "content": "The nucleoside triphosphatase activities of the nuclear envelopes from rat liver, pig liver and simian-virus-40-transformed mouse-embryo 3T3 cells were shown to exhibit similar parperties. All three preparations hydrolyse ATP, 2'-dATP, 3'-dATP, GTP, CTP and UTP in the presence of Mg2+, Ca2+, Mn2+ and Co2+ with a pH optimum of 8.0, are sensitive to inhibition by mercurials, arsenicals, quercetin, proflavin and adenosine 5'-[gamma-thio]triphosphate and are partially inactivated by exposure to high ionic strength. The kinetic behaviour is similar for all substrates irrespective of the source of material. The typical Eadie-Hofstee plot, which is concave upwards at pH 8.0 when the ionic strength is 20mM, becomes linear when the pH is increased to 8.5 or the ionic strength to 160mM. The overall evidence, particularly the labelling of only one polypeptide by [gamma-32P]ATP, suggests that under the conditions of preparation and assay used only one class of nucleoside triphosphatase active sites is detectable in nuclear envelopes. The importance of these results for an understanding of the role of the enzyme in vivo is discussed.", "contents": "Properties of mammalian nuclear-envelope nucleoside triphosphatase. The nucleoside triphosphatase activities of the nuclear envelopes from rat liver, pig liver and simian-virus-40-transformed mouse-embryo 3T3 cells were shown to exhibit similar parperties. All three preparations hydrolyse ATP, 2'-dATP, 3'-dATP, GTP, CTP and UTP in the presence of Mg2+, Ca2+, Mn2+ and Co2+ with a pH optimum of 8.0, are sensitive to inhibition by mercurials, arsenicals, quercetin, proflavin and adenosine 5'-[gamma-thio]triphosphate and are partially inactivated by exposure to high ionic strength. The kinetic behaviour is similar for all substrates irrespective of the source of material. The typical Eadie-Hofstee plot, which is concave upwards at pH 8.0 when the ionic strength is 20mM, becomes linear when the pH is increased to 8.5 or the ionic strength to 160mM. The overall evidence, particularly the labelling of only one polypeptide by [gamma-32P]ATP, suggests that under the conditions of preparation and assay used only one class of nucleoside triphosphatase active sites is detectable in nuclear envelopes. The importance of these results for an understanding of the role of the enzyme in vivo is discussed."}
{"id": "PMID:229822", "title": "Affinity chromatography of human plasma low- and high-density lipoproteins. Elution by selective cleavage of a bond in the spacer.", "content": "Human plasma low- and high-density lipoproteins were found to bind to Sepharose gels containing coupled cholesterol or cholic acid. The lipoproteins were bound very strongly, and it was not possible to elute them under non-denaturing conditions. The detergents Triton X-100 and sodium dodecyl sulphate eluted the lipoproteins in partly denatured form. Adsorbents were used where the steroid was coupled through a spacer containing a thiol ester bond. It was thus possible to elute bound lipoproteins by selective cleavage of the bond with hydroxylamine. A small proportion of albumin was the only contaminant detected, the amounts depending on which ligand was used. Low- and high-density lipoproteins were separated by gel filtration. They behaved as did the native molecules when analysed by gel filtration, immunodiffusion, immunoelectrophoresis and electrophoresis in polyacrylamide gradient gels. The high capacity and the selectivity of the adsorbents make them suitable for the removal of lipoproteins from protein solutions.", "contents": "Affinity chromatography of human plasma low- and high-density lipoproteins. Elution by selective cleavage of a bond in the spacer. Human plasma low- and high-density lipoproteins were found to bind to Sepharose gels containing coupled cholesterol or cholic acid. The lipoproteins were bound very strongly, and it was not possible to elute them under non-denaturing conditions. The detergents Triton X-100 and sodium dodecyl sulphate eluted the lipoproteins in partly denatured form. Adsorbents were used where the steroid was coupled through a spacer containing a thiol ester bond. It was thus possible to elute bound lipoproteins by selective cleavage of the bond with hydroxylamine. A small proportion of albumin was the only contaminant detected, the amounts depending on which ligand was used. Low- and high-density lipoproteins were separated by gel filtration. They behaved as did the native molecules when analysed by gel filtration, immunodiffusion, immunoelectrophoresis and electrophoresis in polyacrylamide gradient gels. The high capacity and the selectivity of the adsorbents make them suitable for the removal of lipoproteins from protein solutions."}
{"id": "PMID:229823", "title": "Polyamines and cellular adenosine 3' :5'-cyclic monophosphate.", "content": "The effect of polyamines on the cellular concentrations of cyclic AMP was studied. It was shown that 1 microM-spermine caused a decrease in cyclic AMP in chick-embryo heart cells, chick-embryo fibroblasts, neuroblastoma, glioma and neuroblastoma-glioma hybrid cells, grown in culture. A similar decrease was observed when polyamines were added to cells in the presence of a phosphodiesterase inhibitor or after stimulating the cells with various hormones. Noradrenaline was used in cultures of heart cells, prostaglandin E1 and adenosine for neuroblastoma and neuroblastoma-glioma hybrids, whereas isoproterenol was used for the stimulation of glioma cells. Polyamines at higher concentrations were either without effect or caused a slight increase in cyclic AMP. Spermidine (10 microM) also caused a decrease in cellular cyclic AMP, as did 0.1 microM-putrescine. It is suggested that the effect of polyamines on cellular cyclic AMP may be explained by the effect of these polycations on the activity of cellular phosphodiesterase.", "contents": "Polyamines and cellular adenosine 3' :5'-cyclic monophosphate. The effect of polyamines on the cellular concentrations of cyclic AMP was studied. It was shown that 1 microM-spermine caused a decrease in cyclic AMP in chick-embryo heart cells, chick-embryo fibroblasts, neuroblastoma, glioma and neuroblastoma-glioma hybrid cells, grown in culture. A similar decrease was observed when polyamines were added to cells in the presence of a phosphodiesterase inhibitor or after stimulating the cells with various hormones. Noradrenaline was used in cultures of heart cells, prostaglandin E1 and adenosine for neuroblastoma and neuroblastoma-glioma hybrids, whereas isoproterenol was used for the stimulation of glioma cells. Polyamines at higher concentrations were either without effect or caused a slight increase in cyclic AMP. Spermidine (10 microM) also caused a decrease in cellular cyclic AMP, as did 0.1 microM-putrescine. It is suggested that the effect of polyamines on cellular cyclic AMP may be explained by the effect of these polycations on the activity of cellular phosphodiesterase."}
{"id": "PMID:229824", "title": "Phosphatidylinositol metabolism in rat hepatocytes stimulated by glycogenolytic hormones. Effects of angiotensin, vasopressin, adrenaline, ionophore A23187 and calcium-ion deprivation.", "content": "1. The effects on phosphatidylinositol metabolism of three Ca(2+)-mobilizing glycogenolytic hormones, namely angiotensin, vasopressin and adrenaline, have been investigated by using rat hepatocytes. 2. All three hormones stimulate both phosphatidylinositol breakdown and the labelling of this lipid with (32)P. 3. The response to angiotensin occurs quickly, requires a high concentration of the hormone and is prevented by [1-sarcosine, 8-isoleucine]angiotensin, a specific angiotensin antagonist that does not prevent the responses to vasopressin and to adrenaline. This response therefore seems to be mediated by angiotensin-specific receptors. 4. [1-Deaminocysteine,2-phenylalanine,7-(3,4-didehydroproline),8-arginine] vasopressin, a vasopressin analogue with enhanced antidiuretic potency, is relatively ineffective at stimulating phosphatidylinositol metabolism. This suggests that the hepatic vasopressin receptors that stimulate phosphatidylinositol breakdown are different in their ligand selectivity from the antidiuretic vasopressin receptors that activate renal adenylate cyclase. 5. Incubation of hepatocytes with ionophore A23187, a bivalent-cation ionophore, neither mimicked nor appreciably changed the effects of vasopressin on phosphatidylinositol metabolism, suggesting that phosphatidylinositol breakdown is not controlled by changes in the cytosol Ca(2+) concentration. This conclusion was supported by the observation that hormonal stimulation of phosphatidylinositol breakdown and resynthesis persists in cells incubated for a substantial period in EGTA, although this treatment somewhat decreased the phosphatidylinositol response of the hepatocyte. The phosphatidylinositol response of the hepatocyte therefore appears not to be controlled by changes in cytosol [Ca(2+)], despite the fact that this ion is thought to be the second messenger by which the same hormones control glycogenolysis. 6. These results may be an indication that phosphatidylinositol breakdown is an integral reaction in the stimulus-response coupling sequence(s) that link(s) activation of alpha-adrenergic, vasopressin and angiotensin receptors to mobilization of Ca(2+) in the rat hepatocyte.", "contents": "Phosphatidylinositol metabolism in rat hepatocytes stimulated by glycogenolytic hormones. Effects of angiotensin, vasopressin, adrenaline, ionophore A23187 and calcium-ion deprivation. 1. The effects on phosphatidylinositol metabolism of three Ca(2+)-mobilizing glycogenolytic hormones, namely angiotensin, vasopressin and adrenaline, have been investigated by using rat hepatocytes. 2. All three hormones stimulate both phosphatidylinositol breakdown and the labelling of this lipid with (32)P. 3. The response to angiotensin occurs quickly, requires a high concentration of the hormone and is prevented by [1-sarcosine, 8-isoleucine]angiotensin, a specific angiotensin antagonist that does not prevent the responses to vasopressin and to adrenaline. This response therefore seems to be mediated by angiotensin-specific receptors. 4. [1-Deaminocysteine,2-phenylalanine,7-(3,4-didehydroproline),8-arginine] vasopressin, a vasopressin analogue with enhanced antidiuretic potency, is relatively ineffective at stimulating phosphatidylinositol metabolism. This suggests that the hepatic vasopressin receptors that stimulate phosphatidylinositol breakdown are different in their ligand selectivity from the antidiuretic vasopressin receptors that activate renal adenylate cyclase. 5. Incubation of hepatocytes with ionophore A23187, a bivalent-cation ionophore, neither mimicked nor appreciably changed the effects of vasopressin on phosphatidylinositol metabolism, suggesting that phosphatidylinositol breakdown is not controlled by changes in the cytosol Ca(2+) concentration. This conclusion was supported by the observation that hormonal stimulation of phosphatidylinositol breakdown and resynthesis persists in cells incubated for a substantial period in EGTA, although this treatment somewhat decreased the phosphatidylinositol response of the hepatocyte. The phosphatidylinositol response of the hepatocyte therefore appears not to be controlled by changes in cytosol [Ca(2+)], despite the fact that this ion is thought to be the second messenger by which the same hormones control glycogenolysis. 6. These results may be an indication that phosphatidylinositol breakdown is an integral reaction in the stimulus-response coupling sequence(s) that link(s) activation of alpha-adrenergic, vasopressin and angiotensin receptors to mobilization of Ca(2+) in the rat hepatocyte."}
{"id": "PMID:229825", "title": "Corticotropin regulation of the synthesis of a specific rat adrenal cytosolic protein. Effects of hypophysectomy and actinomycin D.", "content": "The mechanism of corticotropin stimulation of the synthesis of a specific rat adrenal cytosolic protein was investigated. This protein (protein E) has a mol.wt. of approx. 30000. It is detected by polyacrylamide-gel electrophoresis of cytosol prepared from adrenal slices from rats treated with corticotropin in vivo and control rats, the slices being incubated with [(3)H]- and [(14)C]-leucine respectively. In rats 1-15 days after hypophysectomy, corticotropin, like dibutyryl cyclic AMP, induces an increase in protein E similar to that induced in control rats, even though both compounds no longer stimulate total protein synthesis. Corticotropin stimulation of protein E synthesis is mediated by cyclic AMP but not by corticosterone, since aminoglutethimide, a steroidogenic inhibitor, does not affect corticotropin stimulation, and dexamethasone alone has no effect. Actinomycin D, when injected in vivo 1h before or after corticotropin injection, prevents the effect of corticotropin on protein E synthesis, which is interpreted as evidence that mRNA synthesis is necessary for the stimulation of protein E synthesis. When injected more than 2h after corticotropin, actinomycin D does not prevent corticotropin stimulation of protein E synthesis, but completely blocks corticotropin stimulation of total protein synthesis. This is interpreted as meaning that, after stimulation of mRNA coding for protein E, corticotropin has no effect on the synthesis of protein E. On the other hand, corticotropin stimulation of protein E synthesis persists after hypophysectomy even though it no longer stimulates total protein synthesis. These data suggest that the factor(s) involved in the synthesis of protein E are more stable than those involved in total protein synthesis.", "contents": "Corticotropin regulation of the synthesis of a specific rat adrenal cytosolic protein. Effects of hypophysectomy and actinomycin D. The mechanism of corticotropin stimulation of the synthesis of a specific rat adrenal cytosolic protein was investigated. This protein (protein E) has a mol.wt. of approx. 30000. It is detected by polyacrylamide-gel electrophoresis of cytosol prepared from adrenal slices from rats treated with corticotropin in vivo and control rats, the slices being incubated with [(3)H]- and [(14)C]-leucine respectively. In rats 1-15 days after hypophysectomy, corticotropin, like dibutyryl cyclic AMP, induces an increase in protein E similar to that induced in control rats, even though both compounds no longer stimulate total protein synthesis. Corticotropin stimulation of protein E synthesis is mediated by cyclic AMP but not by corticosterone, since aminoglutethimide, a steroidogenic inhibitor, does not affect corticotropin stimulation, and dexamethasone alone has no effect. Actinomycin D, when injected in vivo 1h before or after corticotropin injection, prevents the effect of corticotropin on protein E synthesis, which is interpreted as evidence that mRNA synthesis is necessary for the stimulation of protein E synthesis. When injected more than 2h after corticotropin, actinomycin D does not prevent corticotropin stimulation of protein E synthesis, but completely blocks corticotropin stimulation of total protein synthesis. This is interpreted as meaning that, after stimulation of mRNA coding for protein E, corticotropin has no effect on the synthesis of protein E. On the other hand, corticotropin stimulation of protein E synthesis persists after hypophysectomy even though it no longer stimulates total protein synthesis. These data suggest that the factor(s) involved in the synthesis of protein E are more stable than those involved in total protein synthesis."}
{"id": "PMID:229826", "title": "The metabolism of cholecalciferol in the liver of Japanese quail (Coturnix coturnix japonica) with particular reference to the effects of oestrogen.", "content": "1. Studies were carried out in vitro with the livers of Japanese quail that had been fed from hatching on diets supplying their full requirements for vitamin D. 2. 25-Hydroxycholecalciferol was the major metabolite when liver homogenates of egg-laying female and oestrogen-treated quail of both sexes were incubated with [3H]cholecalciferol. 3. Very little 25-hydroxycholecalciferol was generated from liver homogenates of adult male and immature quail. Instead the cholecalciferol was converted into one or more compounds less polar than 25-hydroxycholecalciferol and into a number of highly polar metabolites, some of which were water-soluble. 4. Oestrogen not only stimulated the 25-hydroxylation of cholecalciferol but also protected both cholecalciferol and 25-hydroxycholecalciferol from degradation by the enzymic pathways active in immature and male birds. 5. These actions of oestrogen may be of physiological significance in relation to the high requirements of laying birds for 1,25-dihydroxycholecalciferol to support the intense metabolism of calcium associated with egg-shell calcification.", "contents": "The metabolism of cholecalciferol in the liver of Japanese quail (Coturnix coturnix japonica) with particular reference to the effects of oestrogen. 1. Studies were carried out in vitro with the livers of Japanese quail that had been fed from hatching on diets supplying their full requirements for vitamin D. 2. 25-Hydroxycholecalciferol was the major metabolite when liver homogenates of egg-laying female and oestrogen-treated quail of both sexes were incubated with [3H]cholecalciferol. 3. Very little 25-hydroxycholecalciferol was generated from liver homogenates of adult male and immature quail. Instead the cholecalciferol was converted into one or more compounds less polar than 25-hydroxycholecalciferol and into a number of highly polar metabolites, some of which were water-soluble. 4. Oestrogen not only stimulated the 25-hydroxylation of cholecalciferol but also protected both cholecalciferol and 25-hydroxycholecalciferol from degradation by the enzymic pathways active in immature and male birds. 5. These actions of oestrogen may be of physiological significance in relation to the high requirements of laying birds for 1,25-dihydroxycholecalciferol to support the intense metabolism of calcium associated with egg-shell calcification."}
{"id": "PMID:229827", "title": "Uridine kinase activities in developing, adult and neoplastic rat tissues.", "content": "Uridine kinase activities were found chiefly in the soluble fractions of rat tissues. In normal adults the activities ranged from 13 munits/g in skeletal muscle to 178 munits/g in colon. Enzyme activities in several rat neoplasms were significantly higher (e.g. in a fibrosarcoma, mammary carcinoma, renal carcinoma, pancreatic carcinoma and lymphocytic lymphoma, but not in a fast-growing Morris hepatoma). The activities were not related to tumour growth rates or sizes. In normal foetal liver, lung, brain, heart and kidney, uridine kinase concentrations equalled or exceeded those in the adult homologous tissue, but maximal activities in liver were reached 3--5 days post partum. In suckling rats the intestinal activity decreased substantially immediately after birth and normally did not rise again until late in the third postnatal week. Premature upsurges could be evoked by an injection of cortisol or by starvation of the pups overnight. Pancreatic activity was absent from 1-day-old rats, and only about 5% of the adult activity was reached by day 20; adult activities were attained rapidly after weaning. In pancreas, precocious formation or uridine kinase was elicited by overnight starvation of 2-week-old rats.", "contents": "Uridine kinase activities in developing, adult and neoplastic rat tissues. Uridine kinase activities were found chiefly in the soluble fractions of rat tissues. In normal adults the activities ranged from 13 munits/g in skeletal muscle to 178 munits/g in colon. Enzyme activities in several rat neoplasms were significantly higher (e.g. in a fibrosarcoma, mammary carcinoma, renal carcinoma, pancreatic carcinoma and lymphocytic lymphoma, but not in a fast-growing Morris hepatoma). The activities were not related to tumour growth rates or sizes. In normal foetal liver, lung, brain, heart and kidney, uridine kinase concentrations equalled or exceeded those in the adult homologous tissue, but maximal activities in liver were reached 3--5 days post partum. In suckling rats the intestinal activity decreased substantially immediately after birth and normally did not rise again until late in the third postnatal week. Premature upsurges could be evoked by an injection of cortisol or by starvation of the pups overnight. Pancreatic activity was absent from 1-day-old rats, and only about 5% of the adult activity was reached by day 20; adult activities were attained rapidly after weaning. In pancreas, precocious formation or uridine kinase was elicited by overnight starvation of 2-week-old rats."}
{"id": "PMID:229828", "title": "Importance of mammalian nuclear-envelope nucleoside triphosphatase in nucleo-cytoplasmic transport of ribonucleoproteins.", "content": "The nucleoside triphosphate-stimulated efflux of RNA from isolated nuclei was studied under a range of conditions, and the effects of these conditions on the process were compared with the properties of the nucleoside triphosphatase located in the pore complex. A marked similarity between the rate of efflux and the rate of nucleoside triphosphate hydrolysis was apparent, in terms of substrate specificity, sensitivity to treatment with insolubilized trypsin, kinetics and the effects of increased ionic strength and of many inhibitors. These results are taken, in view of earlier evidence, to suggest that the activity of the nucleoside triphosphatase is a prerequisite for nucleo-cytoplasmic RNA transport in vivo. There are some indications that the nuclear-envelope lipid is also involved in regulating the efflux process.", "contents": "Importance of mammalian nuclear-envelope nucleoside triphosphatase in nucleo-cytoplasmic transport of ribonucleoproteins. The nucleoside triphosphate-stimulated efflux of RNA from isolated nuclei was studied under a range of conditions, and the effects of these conditions on the process were compared with the properties of the nucleoside triphosphatase located in the pore complex. A marked similarity between the rate of efflux and the rate of nucleoside triphosphate hydrolysis was apparent, in terms of substrate specificity, sensitivity to treatment with insolubilized trypsin, kinetics and the effects of increased ionic strength and of many inhibitors. These results are taken, in view of earlier evidence, to suggest that the activity of the nucleoside triphosphatase is a prerequisite for nucleo-cytoplasmic RNA transport in vivo. There are some indications that the nuclear-envelope lipid is also involved in regulating the efflux process."}
{"id": "PMID:229829", "title": "M\u00f6ssbauer spectra of photosystem-I-reaction centres from the blue-green alga Chlorogloea fritschii.", "content": "Substantial amounts of iron have been shown by M\u00f6ssbauer spectroscopy to be present in Photosystem-I preparations from the blue-green alga Chlorogloeta fritschii. Changes in the spectra on chemical reduction provide evidence that some of this iron is very similar to that found in the 4Fe-4S centres of ferredoxins. Such reduced samples also show e.p.r. signals consistent with maximum reduction of iron-sulphur centres A and B of Photosystem I. An unchanged component in the spectra indicates, assuming all centres A and B are reduced, the presence of another iron-containing species.", "contents": "M\u00f6ssbauer spectra of photosystem-I-reaction centres from the blue-green alga Chlorogloea fritschii. Substantial amounts of iron have been shown by M\u00f6ssbauer spectroscopy to be present in Photosystem-I preparations from the blue-green alga Chlorogloeta fritschii. Changes in the spectra on chemical reduction provide evidence that some of this iron is very similar to that found in the 4Fe-4S centres of ferredoxins. Such reduced samples also show e.p.r. signals consistent with maximum reduction of iron-sulphur centres A and B of Photosystem I. An unchanged component in the spectra indicates, assuming all centres A and B are reduced, the presence of another iron-containing species."}
{"id": "PMID:229867", "title": "Chemotherapeutically active anthraquinones. I. Aminoanthraquinones.", "content": "Basically substituted 2,6-diacetaminoanthraquinones proved to have an interesting in vivo effect against Entameba histolytica, but this effect was markedly exceeded by that of the series of the 2,6-diamidinoanthraquinones. A number of compounds of this series revealed a significantly stronger extraintestinal effect in the golden hamster than the standard amebicides metronidazole and tinidazole, but they were not superior to these compounds in their trichomonacidal effect, which was in general only a moderate one. In both substance classes, the amebicidal effect was confined to 2,6-disubstitution. Variations of the anthraquinone system resulted in a loss of activity. The structure-activity relationships are discussed.", "contents": "Chemotherapeutically active anthraquinones. I. Aminoanthraquinones. Basically substituted 2,6-diacetaminoanthraquinones proved to have an interesting in vivo effect against Entameba histolytica, but this effect was markedly exceeded by that of the series of the 2,6-diamidinoanthraquinones. A number of compounds of this series revealed a significantly stronger extraintestinal effect in the golden hamster than the standard amebicides metronidazole and tinidazole, but they were not superior to these compounds in their trichomonacidal effect, which was in general only a moderate one. In both substance classes, the amebicidal effect was confined to 2,6-disubstitution. Variations of the anthraquinone system resulted in a loss of activity. The structure-activity relationships are discussed."}
{"id": "PMID:229868", "title": "[The influence of ether anesthesia in white mice on the contents of cyclic nucleotides in their brain and of cyclic nucleotides and glycogen in their liver (author's transl)].", "content": "During ether narcosis (10% diethyl ether v/v) of 30 min in white mice, the brain content of cAMP and cGMP is significantly diminished. By contrast, the liver cAMP and cGMP concentrations are increased 5 and 30 min after beginning narcosis but there is no or little difference, respectively, as compared to controls after 60 min. Liver glycogen content is elevated after 5 min but is diminished after 30 and 60 min as compared to controls. Pretreatment of the animals with the alpha-blocking agent phentolamine and the beta-blocking agent propranolol, respectively, prevents neither the increase in liver cAMP nor the decrease in liver glycogen during ether narcosis. It may be assumed that the changes in the liver and brain contents of cAMP and cGMP during ether application are due to physico-chemical alterations at the cell membrane which result in changes of the activity of the enzymes adenylate cyclase and guanylate cyclase in brain and liver tissue.", "contents": "[The influence of ether anesthesia in white mice on the contents of cyclic nucleotides in their brain and of cyclic nucleotides and glycogen in their liver (author's transl)]. During ether narcosis (10% diethyl ether v/v) of 30 min in white mice, the brain content of cAMP and cGMP is significantly diminished. By contrast, the liver cAMP and cGMP concentrations are increased 5 and 30 min after beginning narcosis but there is no or little difference, respectively, as compared to controls after 60 min. Liver glycogen content is elevated after 5 min but is diminished after 30 and 60 min as compared to controls. Pretreatment of the animals with the alpha-blocking agent phentolamine and the beta-blocking agent propranolol, respectively, prevents neither the increase in liver cAMP nor the decrease in liver glycogen during ether narcosis. It may be assumed that the changes in the liver and brain contents of cAMP and cGMP during ether application are due to physico-chemical alterations at the cell membrane which result in changes of the activity of the enzymes adenylate cyclase and guanylate cyclase in brain and liver tissue."}
{"id": "PMID:229869", "title": "Collagenase-solubilized lipoprotein--glycosaminoglycan complexes of human aortic fibrous plaque lesions.", "content": "The interaction of lipoproteins and arterial connective tissue macromolecules was studied using human atherosclerotic plaque tissues. After extraction with 0.15 M NaCl, the tissues were repeatedly digested with collagenase followed by elastase. The collagenase-solubilized lipoprotein--GAG complexes were isolated by gel-filtration and ultracentrifugation and analyzed for lipids, GAG and protein. While extraction by 0.15 M NaCl released only about 13% of the total cholesterol from the tissues, subsequent digestions by collagenase and elastase yielded 60% and 17% cholesterol, respectively. Both 0.15 M NaCl and collagenase treatment released equal amounts of GAG and accounted for 84% of the total GAG. Immunologically, lipoproteins resembled serum apoB-containing lipoproteins. Bio-Gel A-50m column chromatography of collagenase-extracted materials gave a single peak which contained lipoproteins of 1.006 and 1.063 floating densities, GAG and hydroxyproline. Hyaluronic acid (HA) and chondroitin 6-sulfate were identified; HA was the major GAG. Although the precise nature of the interaction of arterial connective tissue components with lipoproteins is not completely understood, isolation of such complexes indicates the importance of these macromolecules in sequestration of lipoproteins.", "contents": "Collagenase-solubilized lipoprotein--glycosaminoglycan complexes of human aortic fibrous plaque lesions. The interaction of lipoproteins and arterial connective tissue macromolecules was studied using human atherosclerotic plaque tissues. After extraction with 0.15 M NaCl, the tissues were repeatedly digested with collagenase followed by elastase. The collagenase-solubilized lipoprotein--GAG complexes were isolated by gel-filtration and ultracentrifugation and analyzed for lipids, GAG and protein. While extraction by 0.15 M NaCl released only about 13% of the total cholesterol from the tissues, subsequent digestions by collagenase and elastase yielded 60% and 17% cholesterol, respectively. Both 0.15 M NaCl and collagenase treatment released equal amounts of GAG and accounted for 84% of the total GAG. Immunologically, lipoproteins resembled serum apoB-containing lipoproteins. Bio-Gel A-50m column chromatography of collagenase-extracted materials gave a single peak which contained lipoproteins of 1.006 and 1.063 floating densities, GAG and hydroxyproline. Hyaluronic acid (HA) and chondroitin 6-sulfate were identified; HA was the major GAG. Although the precise nature of the interaction of arterial connective tissue components with lipoproteins is not completely understood, isolation of such complexes indicates the importance of these macromolecules in sequestration of lipoproteins."}
{"id": "PMID:229870", "title": "Effect of risk factors and antirheumatic drugs on the proliferation of aortic wall cells.", "content": "The proliferation of aortic smooth muscle cells (ASMC) of Wistar rats, impaired by risk factors such as arterial hypertension, diabetes mellitus, atherogenic diet and staphylolysin injections and of normal Wistar rats treated with antirheumatic drugs such as prednisolone and acetylsalicylic acid was investigated. The cells of these animals were cultivated, subcultivated, and in the 2nd subcultures the cell numbers/5 ml medium were counted by means of Coulter Counter, and the cells were incubated with [3H]thymidine and the percentage of labelling in 100 or 1000 counted cells was stated. The effect of risk factors such as LDL and staphylolysin and of antirheumatic drugs such as prednisolone, acetylsalicylic acid, D-penicillamine and chloroquine added to the 2nd subcultures of cultivated ASMC of normal minipigs was investigated by the same method. The proliferation of cultivated ASMC of rats impaired by risk factors was accelerated. The proliferation of cultivated ASMC of rats treated with antirheumatic drugs was inhibited. The proliferation of ASMC of minipigs in the 2nd subcultures was activated by addition of risk factors and inhibited by addition of antirheumatic drugs. Antirheumatic drugs given to the rats and added to the medium of the 2nd subcultures of ASMC of normal minipigs inhibit the acceleration of ASMC proliferation induced by simultaneously given risk factors. The proposal to augment up our arsenal of the hitherto existing preventive and therapeutical measures by the application of antirheumatic drugs based on the experimental models referred to is supported by the result of a limited prospective double-blind-study of a sample of 133 male patients after myocardial infarction. The most remarkable result that the acceleration of the ASMC proliferation, the real pathologic process of arteriosclerosis, is inhibited by the application of antirheumatic drugs, at exactly the same time as the acceleration of the fibroblast proliferation, the real pathologic process in rheumatic diseases--ASMC and fibroblast, both being mesenchymal cells--recommends the use of these drugs in the prevention and therapy of human arteriosclerosis. The surprising result of our in-vivo experiments, that the acceleration of the growth of the ASMC induced by risk factors and the inhibition of the growth induced by antirheumatic drugs persist in the subcultures, is explained by the \"selection theory\" that there are dissimilar kinds of ASMC in normal arteries and that they react differently.", "contents": "Effect of risk factors and antirheumatic drugs on the proliferation of aortic wall cells. The proliferation of aortic smooth muscle cells (ASMC) of Wistar rats, impaired by risk factors such as arterial hypertension, diabetes mellitus, atherogenic diet and staphylolysin injections and of normal Wistar rats treated with antirheumatic drugs such as prednisolone and acetylsalicylic acid was investigated. The cells of these animals were cultivated, subcultivated, and in the 2nd subcultures the cell numbers/5 ml medium were counted by means of Coulter Counter, and the cells were incubated with [3H]thymidine and the percentage of labelling in 100 or 1000 counted cells was stated. The effect of risk factors such as LDL and staphylolysin and of antirheumatic drugs such as prednisolone, acetylsalicylic acid, D-penicillamine and chloroquine added to the 2nd subcultures of cultivated ASMC of normal minipigs was investigated by the same method. The proliferation of cultivated ASMC of rats impaired by risk factors was accelerated. The proliferation of cultivated ASMC of rats treated with antirheumatic drugs was inhibited. The proliferation of ASMC of minipigs in the 2nd subcultures was activated by addition of risk factors and inhibited by addition of antirheumatic drugs. Antirheumatic drugs given to the rats and added to the medium of the 2nd subcultures of ASMC of normal minipigs inhibit the acceleration of ASMC proliferation induced by simultaneously given risk factors. The proposal to augment up our arsenal of the hitherto existing preventive and therapeutical measures by the application of antirheumatic drugs based on the experimental models referred to is supported by the result of a limited prospective double-blind-study of a sample of 133 male patients after myocardial infarction. The most remarkable result that the acceleration of the ASMC proliferation, the real pathologic process of arteriosclerosis, is inhibited by the application of antirheumatic drugs, at exactly the same time as the acceleration of the fibroblast proliferation, the real pathologic process in rheumatic diseases--ASMC and fibroblast, both being mesenchymal cells--recommends the use of these drugs in the prevention and therapy of human arteriosclerosis. The surprising result of our in-vivo experiments, that the acceleration of the growth of the ASMC induced by risk factors and the inhibition of the growth induced by antirheumatic drugs persist in the subcultures, is explained by the \"selection theory\" that there are dissimilar kinds of ASMC in normal arteries and that they react differently."}
{"id": "PMID:229871", "title": "Cholesterol metabolism in non-obese women--Failure of physical conditioning to alter levels of high density lipoprotein cholesterol.", "content": "The effects of a 6-week program of vigorous exercise were studied in 14 non-obese females aged 22--26. Preceding and following a regimen consisting of 30--45 min of jogging 5 days per week, treadmill performance, body weight, total plasma cholesterol, and plasma high density lipoprotein (HDL) cholesterol were assessed. Aerobic performance improved markedly after training as demonstrated by a reduced heart rate at each submaximal treadmill workload, and by an increase in maximal attainable workload. In the absence of a significant change in body weight, total cholesterol fell significantly after training (171 +/- 6 vs 161 +/- 5 mg/dl, P less than 0.05) whereas HDL cholesterol was not significantly altered (63 +/- 5 vs 58 +/- 3 mg/dl). The ratio of total cholesterol to HDL cholesterol fell insignificantly (2.92 +/- 0.19 vs 2.86 +/- 0.14). Our findings differ from prior reports of elevations of high density lipoprotein levels following physical conditioning in men. We suggest that hormonal or other factors leading to higher baseline levels of HDL in women counteract the expected alterations in lipoprotein metabolism induced by physical training.", "contents": "Cholesterol metabolism in non-obese women--Failure of physical conditioning to alter levels of high density lipoprotein cholesterol. The effects of a 6-week program of vigorous exercise were studied in 14 non-obese females aged 22--26. Preceding and following a regimen consisting of 30--45 min of jogging 5 days per week, treadmill performance, body weight, total plasma cholesterol, and plasma high density lipoprotein (HDL) cholesterol were assessed. Aerobic performance improved markedly after training as demonstrated by a reduced heart rate at each submaximal treadmill workload, and by an increase in maximal attainable workload. In the absence of a significant change in body weight, total cholesterol fell significantly after training (171 +/- 6 vs 161 +/- 5 mg/dl, P less than 0.05) whereas HDL cholesterol was not significantly altered (63 +/- 5 vs 58 +/- 3 mg/dl). The ratio of total cholesterol to HDL cholesterol fell insignificantly (2.92 +/- 0.19 vs 2.86 +/- 0.14). Our findings differ from prior reports of elevations of high density lipoprotein levels following physical conditioning in men. We suggest that hormonal or other factors leading to higher baseline levels of HDL in women counteract the expected alterations in lipoprotein metabolism induced by physical training."}
{"id": "PMID:229872", "title": "Marked increase in high density lipoproteins in mountaineers.", "content": "Apoprotein-AI concentrations were measured in whole blood in 13 male mountaineers before, during and after a strenuous climb of 8 weeks' duration. The AI concentration almost doubled in 3 weeks and remained elevated at that level for the full period of the climb. This study demonstrates the rapid rate at which high density lipoproteins can rise and the very high levels (148 +/- 29 mg/dl in whole blood) that can be reached. The rise can be attributed at least in part to exercise though other factors such as exposure to cold, hypoxia and mental stress might also have contributed.", "contents": "Marked increase in high density lipoproteins in mountaineers. Apoprotein-AI concentrations were measured in whole blood in 13 male mountaineers before, during and after a strenuous climb of 8 weeks' duration. The AI concentration almost doubled in 3 weeks and remained elevated at that level for the full period of the climb. This study demonstrates the rapid rate at which high density lipoproteins can rise and the very high levels (148 +/- 29 mg/dl in whole blood) that can be reached. The rise can be attributed at least in part to exercise though other factors such as exposure to cold, hypoxia and mental stress might also have contributed."}
{"id": "PMID:229873", "title": "Fibrinogen and low density lipoprotein in the development of cerebral atherosclerosis.", "content": "Cerebral arteries from 65 human subjects were examined by immunofluorescence, using antisera against human fibrinogen and low density lipoprotein (LDL). Deposition of fibrinogen and LDL was most frequent at the bifurcation of the middle cerebral arteries and least in the basilar arteries in all age groups. In general, deposition of LDL was associated with deposition of fibrinogen, and lone deposition of LDL in the absence of fibrinogen was only rarely seen. Fibrinogen was scattered in the intercellular spaces, and located in the inner layer or edges of the thickened intima of the bifurcation with increasing plaque formation. Fibrinogen was observed even in the subendothelial region of the uninvolved intima at the bifurcations. LDL was present in the cytoplasm of the endothelial cells in the earliest stage, and it increased in the extracellular stroma with increase in intimal thickening, corresponding closely to the distribution of perifibous oil-red-O-stained lipids. No LDL was detected in the uninvolved intima. The observations suggest that deposition of fibrinogen in the intima might precede LDL deposition and possibly play a more important role than LDL in the development of atherosclerotic lesions in the cerebral arteries, especially in their early stage. Severe atherosclerosis at the bifurcations may be in part due to increased permeation of these plasma proteins, possibly as a result of hemodynamic stress.", "contents": "Fibrinogen and low density lipoprotein in the development of cerebral atherosclerosis. Cerebral arteries from 65 human subjects were examined by immunofluorescence, using antisera against human fibrinogen and low density lipoprotein (LDL). Deposition of fibrinogen and LDL was most frequent at the bifurcation of the middle cerebral arteries and least in the basilar arteries in all age groups. In general, deposition of LDL was associated with deposition of fibrinogen, and lone deposition of LDL in the absence of fibrinogen was only rarely seen. Fibrinogen was scattered in the intercellular spaces, and located in the inner layer or edges of the thickened intima of the bifurcation with increasing plaque formation. Fibrinogen was observed even in the subendothelial region of the uninvolved intima at the bifurcations. LDL was present in the cytoplasm of the endothelial cells in the earliest stage, and it increased in the extracellular stroma with increase in intimal thickening, corresponding closely to the distribution of perifibous oil-red-O-stained lipids. No LDL was detected in the uninvolved intima. The observations suggest that deposition of fibrinogen in the intima might precede LDL deposition and possibly play a more important role than LDL in the development of atherosclerotic lesions in the cerebral arteries, especially in their early stage. Severe atherosclerosis at the bifurcations may be in part due to increased permeation of these plasma proteins, possibly as a result of hemodynamic stress."}
{"id": "PMID:229874", "title": "Incorporation of polyenephosphatidylcholine into serum lipoproteins after oral or intravenous administration.", "content": "Radioactive polyenephosphatidycholine (PPC) was injected i.v. in dogs, rats and rabbits. In addition, PPC was administered orally to dogs and rats. The incorporation of the PPC applied into serum lipoproteins was determined. After i.v. injection in dogs approximately 80% of the radioactive dose was transported by HDL. Only around 50% of the dose was found, however, in the HDL fraction of rats and rabbits. Radiochemical analyses provided a quantitative determination of the time course of PPC incorporation into HDL as well as of the metabolites of PPC. After in vitro incubation with rat and human serum PPC was incorporated into HDL by approximately 50% of the applied dose and by 5--14% into LDL, by approximately 15% into VLDL and by 20--30% into other serum constituents. In vitro incubation of PPC with human HDL yielded the complete incorporation into this lipoprotein fraction.", "contents": "Incorporation of polyenephosphatidylcholine into serum lipoproteins after oral or intravenous administration. Radioactive polyenephosphatidycholine (PPC) was injected i.v. in dogs, rats and rabbits. In addition, PPC was administered orally to dogs and rats. The incorporation of the PPC applied into serum lipoproteins was determined. After i.v. injection in dogs approximately 80% of the radioactive dose was transported by HDL. Only around 50% of the dose was found, however, in the HDL fraction of rats and rabbits. Radiochemical analyses provided a quantitative determination of the time course of PPC incorporation into HDL as well as of the metabolites of PPC. After in vitro incubation with rat and human serum PPC was incorporated into HDL by approximately 50% of the applied dose and by 5--14% into LDL, by approximately 15% into VLDL and by 20--30% into other serum constituents. In vitro incubation of PPC with human HDL yielded the complete incorporation into this lipoprotein fraction."}
{"id": "PMID:229875", "title": "Increase of serum high density lipoprotein with progression and regression of aortic lipid deposition in rats.", "content": "The progression and regression of aortic lipid deposition was studied in male ExHC rats. Rats in the progression group were fed an atherogenic diet containing 2% cholesterol, 0.4% sodium cholate and 10% olive oil for periods up to 32 weeks. Rats in the regression group were first fed the atherogenic diet for 16 weeks, and then maintained on a basal low cholesterol diet. Half the rats were killed at 4 weeks and the other half at 16 weeks after cessation of the atherogenic diet. Rat aortas of the progression group contained progressively more lipid pari passu with the duration of cholesterol feeding, but connective-tissue proliferation was absent. Deposited lipid in the aorta of cholesterol-fed rats disappeared very slowly after the rats were returned to the basal diet. serum HDL decreased in the hypercholesterolemic ExHC rats fed the atherogenic diet for 4 weeks. By contrast, serum HDL and apo A-I increased in both hypercholesterolemic ExHC rats fed the atherogenic diet for 32 weeks and slightly hypercholesterolemic ExHC rats fed the basal diet for 16 weeks in the regression period.", "contents": "Increase of serum high density lipoprotein with progression and regression of aortic lipid deposition in rats. The progression and regression of aortic lipid deposition was studied in male ExHC rats. Rats in the progression group were fed an atherogenic diet containing 2% cholesterol, 0.4% sodium cholate and 10% olive oil for periods up to 32 weeks. Rats in the regression group were first fed the atherogenic diet for 16 weeks, and then maintained on a basal low cholesterol diet. Half the rats were killed at 4 weeks and the other half at 16 weeks after cessation of the atherogenic diet. Rat aortas of the progression group contained progressively more lipid pari passu with the duration of cholesterol feeding, but connective-tissue proliferation was absent. Deposited lipid in the aorta of cholesterol-fed rats disappeared very slowly after the rats were returned to the basal diet. serum HDL decreased in the hypercholesterolemic ExHC rats fed the atherogenic diet for 4 weeks. By contrast, serum HDL and apo A-I increased in both hypercholesterolemic ExHC rats fed the atherogenic diet for 32 weeks and slightly hypercholesterolemic ExHC rats fed the basal diet for 16 weeks in the regression period."}
{"id": "PMID:229876", "title": "Effect of smoking on serum levels of HDL apoproteins.", "content": "Quantitative determination of HDL apoproteins in serum from 97 healthy men showed a significantly lower apoA-I and apoA-II level in smokers than in non-smokers. Also a significant, negative correlation was found between the apoA-I or apoA-II levels, and the number of cigarettes smoked per day.", "contents": "Effect of smoking on serum levels of HDL apoproteins. Quantitative determination of HDL apoproteins in serum from 97 healthy men showed a significantly lower apoA-I and apoA-II level in smokers than in non-smokers. Also a significant, negative correlation was found between the apoA-I or apoA-II levels, and the number of cigarettes smoked per day."}
{"id": "PMID:229878", "title": "Lipoprotein lipids in chronic renal failure and haemodialysis. The influence of etiology and implications for atherogenesis.", "content": "Lipoprotein lipid analysis has been carried out in 39 women and 28 men with chronic renal failure on haemodialysis. The results have been analysed in relation to the etiology of the renal disease and compared with those obtained in age- and sex-matched controls and in triglyceride-matched controls. Serum cholesterol was normal or low in glomerulonephritis but was normal in analgesic nephropathy. Serum triglycerides and VLDL lipids were raised uniformly regardless of the etiology of the renal disease. LDL triglyceride and HDL triglyceride were also raised. LDL cholesterol and phospholipid were low in glomerulonephritis but were normal in analgesic nephropathy. HDL cholesterol was reduced in both male and female patients regardless of etiology, statistical significance was not reached for the women. The ratio of esterified to free cholesterol tended to be reduced in all the lipoproteins regardless of sex or etiology but the changes were not significant in all groups. Comparison of the lipid abnormalities with those found in other hyperlipidaemic states suggests that the lipid disorders found in chronic renal failure are probably insufficient to explain the rapid development of vascular disease which has been reported.", "contents": "Lipoprotein lipids in chronic renal failure and haemodialysis. The influence of etiology and implications for atherogenesis. Lipoprotein lipid analysis has been carried out in 39 women and 28 men with chronic renal failure on haemodialysis. The results have been analysed in relation to the etiology of the renal disease and compared with those obtained in age- and sex-matched controls and in triglyceride-matched controls. Serum cholesterol was normal or low in glomerulonephritis but was normal in analgesic nephropathy. Serum triglycerides and VLDL lipids were raised uniformly regardless of the etiology of the renal disease. LDL triglyceride and HDL triglyceride were also raised. LDL cholesterol and phospholipid were low in glomerulonephritis but were normal in analgesic nephropathy. HDL cholesterol was reduced in both male and female patients regardless of etiology, statistical significance was not reached for the women. The ratio of esterified to free cholesterol tended to be reduced in all the lipoproteins regardless of sex or etiology but the changes were not significant in all groups. Comparison of the lipid abnormalities with those found in other hyperlipidaemic states suggests that the lipid disorders found in chronic renal failure are probably insufficient to explain the rapid development of vascular disease which has been reported."}
{"id": "PMID:229879", "title": "HDL lipids in close relatives of coronary heart disease patients. Environmental and genetic influences.", "content": "Female first-degree relatives of CHD patients differed, after the age of forty, from the normal control population by their low HDL cholesterol. Between the ages of 20 and 40 years a slight but significant increase in HDL triglycerides was observed. Except for hormonal contraception which induces significant lowering of HDL cholesterol in the first degree relatives, the observed differences in HDL lipids did not seem related to environmental factors but rather to be genetically determined. In contrast, the low HDL cholesterol observed in the wives of the CHD patients appeared to be related to differences in alcohol intake.", "contents": "HDL lipids in close relatives of coronary heart disease patients. Environmental and genetic influences. Female first-degree relatives of CHD patients differed, after the age of forty, from the normal control population by their low HDL cholesterol. Between the ages of 20 and 40 years a slight but significant increase in HDL triglycerides was observed. Except for hormonal contraception which induces significant lowering of HDL cholesterol in the first degree relatives, the observed differences in HDL lipids did not seem related to environmental factors but rather to be genetically determined. In contrast, the low HDL cholesterol observed in the wives of the CHD patients appeared to be related to differences in alcohol intake."}
{"id": "PMID:229880", "title": "Sex hormones and high density lipoproteins in healthy males.", "content": "The serum concentrations of testosterone, androstenedione, oestradiol and total low polar oestrogens, mainly oestradiol and oestrone, were measured in 26 healthy male subjects. The subjects were divided into two groups each of them with low (less than 1.04 mmol/l) and high (greater than 1.56 mmol/l) levels of serum HDL cholesterol. The group with high HDL cholesterol had significantly higher testosterone than the other group. Positive correlations were established between HDL cholesterol and testosterone and total cholesterol and testosterone concentration in serum.", "contents": "Sex hormones and high density lipoproteins in healthy males. The serum concentrations of testosterone, androstenedione, oestradiol and total low polar oestrogens, mainly oestradiol and oestrone, were measured in 26 healthy male subjects. The subjects were divided into two groups each of them with low (less than 1.04 mmol/l) and high (greater than 1.56 mmol/l) levels of serum HDL cholesterol. The group with high HDL cholesterol had significantly higher testosterone than the other group. Positive correlations were established between HDL cholesterol and testosterone and total cholesterol and testosterone concentration in serum."}
{"id": "PMID:229881", "title": "In vivo metabolism of esterified cholesterol and apoproteins in rabbit plasma low density lipoproteins.", "content": "Preparations of rabbit low density lipoproteins (LDL) labelled with 3H in the esterified and free cholesterol moieties and with 125I in the apoprotein moiety were injected intravenously into other rabbits. A substantial proportion of the esterified [3H]cholesterol removed from LDL during the first 30 min was recovered in the high density lipoprotein (HDL) fraction, while no such transfer of labelled apoprotein was observed. There was a clear cut differential in the decay of the different LDL components, slowest for the apoprotein, intermediate for esterified cholesterol and fastest for free cholesterol.", "contents": "In vivo metabolism of esterified cholesterol and apoproteins in rabbit plasma low density lipoproteins. Preparations of rabbit low density lipoproteins (LDL) labelled with 3H in the esterified and free cholesterol moieties and with 125I in the apoprotein moiety were injected intravenously into other rabbits. A substantial proportion of the esterified [3H]cholesterol removed from LDL during the first 30 min was recovered in the high density lipoprotein (HDL) fraction, while no such transfer of labelled apoprotein was observed. There was a clear cut differential in the decay of the different LDL components, slowest for the apoprotein, intermediate for esterified cholesterol and fastest for free cholesterol."}
{"id": "PMID:229884", "title": "[Levels of specific antibodies against poliomyelitis virus and degree of immune protection in Umbria population].", "content": "The Authors studied neutralizing antibodies against poliomyelitis wild viruses in a sample of Umbria population. The number of seronegative results for each virus strain was very low (less than 1%). The geometric mean titres were 21.07, 26.72, 19.13 for poliovirus types 1, 2, 3, respectively. The results of this seroepidemiological study shows that the Umbria population is satisfactory protected against the poliomyelitis.", "contents": "[Levels of specific antibodies against poliomyelitis virus and degree of immune protection in Umbria population]. The Authors studied neutralizing antibodies against poliomyelitis wild viruses in a sample of Umbria population. The number of seronegative results for each virus strain was very low (less than 1%). The geometric mean titres were 21.07, 26.72, 19.13 for poliovirus types 1, 2, 3, respectively. The results of this seroepidemiological study shows that the Umbria population is satisfactory protected against the poliomyelitis."}
{"id": "PMID:229885", "title": "[Method for isolation of enteroviruses from edible mollusca].", "content": "A method for recovery of Poliovirus from experimentally inoculated mussels has been evaluated. The method, based on adsorption-elution-acid precipitation of virus particles, allows a recovery of more than 93% of the added virus.", "contents": "[Method for isolation of enteroviruses from edible mollusca]. A method for recovery of Poliovirus from experimentally inoculated mussels has been evaluated. The method, based on adsorption-elution-acid precipitation of virus particles, allows a recovery of more than 93% of the added virus."}
{"id": "PMID:229886", "title": "Na+/K+-dependent adenosinetriphosphatase activity in mammalian kidney.", "content": "Microsomal preparations with Na+/K+-dependent ATPase activity from the outer medulla of rabbit and pig kidney were obtained. Purifications were assaied by centrifugation on sucrose discontinuous gradients and gel-filtration on Sepharose 6B, after detergent incubation. Sodium dodecylsulfate, with ATP as protecting agent, can remove a maximal amount of non specific proteins from the membranes and allows the recovery of a fraction with very high specific activity. The approach to purification by affinity chromatography techniques leads to interesting results, which induce us to pursue the present researchs to applicate an affinity method to Na+/K+-ATPase.", "contents": "Na+/K+-dependent adenosinetriphosphatase activity in mammalian kidney. Microsomal preparations with Na+/K+-dependent ATPase activity from the outer medulla of rabbit and pig kidney were obtained. Purifications were assaied by centrifugation on sucrose discontinuous gradients and gel-filtration on Sepharose 6B, after detergent incubation. Sodium dodecylsulfate, with ATP as protecting agent, can remove a maximal amount of non specific proteins from the membranes and allows the recovery of a fraction with very high specific activity. The approach to purification by affinity chromatography techniques leads to interesting results, which induce us to pursue the present researchs to applicate an affinity method to Na+/K+-ATPase."}
{"id": "PMID:229887", "title": "[Modifications of liver content of cyclic nucleotides in the rat poisoned with white phosphorus].", "content": "In rat liver following white phorphorus poisoning a biphasic increase in cyclic AMP concentration was observed. After a lag period of 1 hour the cyclic AMP content rose to a first peak at 4 hours and to a second peak at 12 hours of intoxication. The cyclic AMP level fell to normal after 24 hours, by which time the cyclic nucleotide concentration was approaching control values. On the contrary, cyclic GMP content was found to the normal level during the different stages of intoxication. Only at 36 hours the cyclic GMP amount appeared significantly increased above the control values. Serum activity of alanine- and aspartate-amino transferases was found changed from 8 hours to 24 hours after poisoning. The serum level of the two enzymes was overlapping the control values after 36 hours. These results are discussed in relation to hepatocyte necrosis following white phosphorus intoxication.", "contents": "[Modifications of liver content of cyclic nucleotides in the rat poisoned with white phosphorus]. In rat liver following white phorphorus poisoning a biphasic increase in cyclic AMP concentration was observed. After a lag period of 1 hour the cyclic AMP content rose to a first peak at 4 hours and to a second peak at 12 hours of intoxication. The cyclic AMP level fell to normal after 24 hours, by which time the cyclic nucleotide concentration was approaching control values. On the contrary, cyclic GMP content was found to the normal level during the different stages of intoxication. Only at 36 hours the cyclic GMP amount appeared significantly increased above the control values. Serum activity of alanine- and aspartate-amino transferases was found changed from 8 hours to 24 hours after poisoning. The serum level of the two enzymes was overlapping the control values after 36 hours. These results are discussed in relation to hepatocyte necrosis following white phosphorus intoxication."}
{"id": "PMID:229888", "title": "Polymyxin B and heart muscle.", "content": "The effects of the polypeptide antibiotic, polymyxin B, on myocardial contractility were studied in t;e isolated rat heart muscle. Five different doses of polymyxin B were tested. There were no changes in contractility with does ranging from the clinical therapeutic value to three times greater. There was an initial increase and then depression with a dose six times greater than the therapeutic dose. There was no direct competitive interaction between polymyxin B and halothane or Ca2+. This suggests that polymyxin B does not depress the myocardium in clinical doses and does not interfere with Ca2+ influx at the myocardial cell membrane.", "contents": "Polymyxin B and heart muscle. The effects of the polypeptide antibiotic, polymyxin B, on myocardial contractility were studied in t;e isolated rat heart muscle. Five different doses of polymyxin B were tested. There were no changes in contractility with does ranging from the clinical therapeutic value to three times greater. There was an initial increase and then depression with a dose six times greater than the therapeutic dose. There was no direct competitive interaction between polymyxin B and halothane or Ca2+. This suggests that polymyxin B does not depress the myocardium in clinical doses and does not interfere with Ca2+ influx at the myocardial cell membrane."}
{"id": "PMID:229891", "title": "Uridine diphosphate galactose 4-epimerase. Alkylation of enzyme-bound diphosphopyridine nucleotide by p-(bromoacetamido)phenyl uridyl pyrophosphate, an active-site-directed irreversible inhibitor.", "content": "When UDP-galactose 4-epimerase is inactivated by p-(bromoacetamido)phenyl uridyl pyrophosphate (BUP), the diphosphopyridine nucleotide (DPN) associated with this enzyme as a tightly bound coenzyme cannot be reduced by substrates or by UMP-activated reduction by glucose. Upon acid denaturation of the inactivated enzyme, the DPN released corresponded to 15-30% of that released from the native enzyme. When the enzyme is inactivated by [14C]BUP, about 80% of the radioactivity bound at the active site is released from the protein upon acid denaturation. When epimerase-[3H]DPN is inactivated with [14C]BUP, the 3H and 14C released from the protein upon denaturation of the complex cochromatograph on DEAE-Sephadex. Experiments with [nicotinamide-4-3H]DPN and [adenine-2,8-3H]DPN show that it is the adenine ring that is alkylated. The data suggest that the adenine ring of DPN in epimerase-DPN may be oriented near the glycosyl-binding subsite of this enzyme. Since the nicotinamide ring must also be near this site, it appears that the DPN may not be in an extended conformation when it is bound at the active site of UDP-galactose 4-epimerase from Escherichia coli.", "contents": "Uridine diphosphate galactose 4-epimerase. Alkylation of enzyme-bound diphosphopyridine nucleotide by p-(bromoacetamido)phenyl uridyl pyrophosphate, an active-site-directed irreversible inhibitor. When UDP-galactose 4-epimerase is inactivated by p-(bromoacetamido)phenyl uridyl pyrophosphate (BUP), the diphosphopyridine nucleotide (DPN) associated with this enzyme as a tightly bound coenzyme cannot be reduced by substrates or by UMP-activated reduction by glucose. Upon acid denaturation of the inactivated enzyme, the DPN released corresponded to 15-30% of that released from the native enzyme. When the enzyme is inactivated by [14C]BUP, about 80% of the radioactivity bound at the active site is released from the protein upon acid denaturation. When epimerase-[3H]DPN is inactivated with [14C]BUP, the 3H and 14C released from the protein upon denaturation of the complex cochromatograph on DEAE-Sephadex. Experiments with [nicotinamide-4-3H]DPN and [adenine-2,8-3H]DPN show that it is the adenine ring that is alkylated. The data suggest that the adenine ring of DPN in epimerase-DPN may be oriented near the glycosyl-binding subsite of this enzyme. Since the nicotinamide ring must also be near this site, it appears that the DPN may not be in an extended conformation when it is bound at the active site of UDP-galactose 4-epimerase from Escherichia coli."}
{"id": "PMID:229892", "title": "Covalent structure of collagen: amino acid sequence of alpha 2-CB5 of chick skin collagen containing the animal collagenase cleavage site.", "content": "The amino acid sequence of the 112 residues from the amino terminus of alpha 2-CB5 from chick skin collagen was determined by automated sequential degradation of intact alpha 2-CB5 and several chymotryptic and tryptic peptides. This segment of the peptide includes the site of the action of animal collagenases. As compared to the sequence around the alpha 1 cleavage site, the alpha 2 sequence is notable for the remarkable constancy of the residues to the amino side and the relative abundance of hydrophobic residues to the carboxyl side of the cleavage site, suggesting that these features are important in the recognition by the enzyme. The sequence of this region of the alpha 2 chain is consistent with the Gly-X-Y triplet structure and the preference of certain residues for either the X or Y position in distribution. However, three of the six residues of leucine were found in the Y position rather than the X position. Leucine residues were found only once in the Y position in the alpha 1 (I) chain. This preference does not appear to hold in the alpha 2 chain.", "contents": "Covalent structure of collagen: amino acid sequence of alpha 2-CB5 of chick skin collagen containing the animal collagenase cleavage site. The amino acid sequence of the 112 residues from the amino terminus of alpha 2-CB5 from chick skin collagen was determined by automated sequential degradation of intact alpha 2-CB5 and several chymotryptic and tryptic peptides. This segment of the peptide includes the site of the action of animal collagenases. As compared to the sequence around the alpha 1 cleavage site, the alpha 2 sequence is notable for the remarkable constancy of the residues to the amino side and the relative abundance of hydrophobic residues to the carboxyl side of the cleavage site, suggesting that these features are important in the recognition by the enzyme. The sequence of this region of the alpha 2 chain is consistent with the Gly-X-Y triplet structure and the preference of certain residues for either the X or Y position in distribution. However, three of the six residues of leucine were found in the Y position rather than the X position. Leucine residues were found only once in the Y position in the alpha 1 (I) chain. This preference does not appear to hold in the alpha 2 chain."}
{"id": "PMID:229893", "title": "Interaction between cytochrome c and cytochrome b5.", "content": "The reduction of cytochrome c by cytochrome b5 was studied over a wide range of ionic strengths in four different buffer systems. The reaction rate decreased linearly as the I1/2 was increased, suggesting that electrostatic interactions are important in the interaction. The ionic strength dependence of the reaction rate was in quantitative agreement with the theory of Wherland & Gray [Wherland, S., & Gray, H.B. (1976) Proc. Natl. Acad. Sci U.S.A. 73, 2950] only if the effective radius of the interaction was 2 A. This indicates that the interaction between the two proteins is best described as the sum of n complementary charge interactions, each involving a specific lysine on cytochrome c and a specific carboxyl group on cytochrome b5. The number of complementary charge interactions, n, was calculated to be five to seven, in agreement with the results of our specific modification studies. Ultracentrifugation and gel permeation techniques were used to demonstrate that cytochrome b5 and cytochrome c formed a stable complex at low ionic strength.", "contents": "Interaction between cytochrome c and cytochrome b5. The reduction of cytochrome c by cytochrome b5 was studied over a wide range of ionic strengths in four different buffer systems. The reaction rate decreased linearly as the I1/2 was increased, suggesting that electrostatic interactions are important in the interaction. The ionic strength dependence of the reaction rate was in quantitative agreement with the theory of Wherland & Gray [Wherland, S., & Gray, H.B. (1976) Proc. Natl. Acad. Sci U.S.A. 73, 2950] only if the effective radius of the interaction was 2 A. This indicates that the interaction between the two proteins is best described as the sum of n complementary charge interactions, each involving a specific lysine on cytochrome c and a specific carboxyl group on cytochrome b5. The number of complementary charge interactions, n, was calculated to be five to seven, in agreement with the results of our specific modification studies. Ultracentrifugation and gel permeation techniques were used to demonstrate that cytochrome b5 and cytochrome c formed a stable complex at low ionic strength."}
{"id": "PMID:229895", "title": "Inhibition of adenylate kinase by P1-(lin-benzo-5'-adenosyl)-P4-(5'-adenosyl) tetraphosphate and P1-(lin-benzo-5'-adenosyl)-P5-(5'-adenosyl pentaphosphate.", "content": "P1-(lin-Benzo-5'-adenosyl)-P5-(5'-adenosyl) penraphosphate and P1-(lin-benzo-5'-adenosyl)-P4-(5'-adenosyl) tetraphosphate have been synthesized from lin-benzoadenosine 5'-monophosphoromorpholidate and adenosine 5'-tetraphosphate and adenosine 5'-triphosphate. These mixed dinucleoside polyphosphates are potent inhibitors of porcine muscle adenylate kinase, with association constants of 2 x 10(5) M-1 for the pentaphosphate and 2 x 10(6) M-1 for the tetraphosphate, respectively, as determined by kinetics and fluorescence experiments. The increase in fluorescence intensities and fluorescence lifetimes of both inhibitors upon binding to adenylate kinase results from a breaking of the intramolecular stacking interaction observed when these ligands are free in solution and implicates their binding to the enzyme in an \"open\" or \"extended\" form. These results and the dimensional requirements of these inhibitors are discussed in relation to our current knowledge of the active site of adenylate kinase and to the known inhibitors of adenylate kinase, P1,P5-bis(5'-adenosyl) pentaphosphate and P1,P4-bis-(5'-adenosyl) tetraphosphate.", "contents": "Inhibition of adenylate kinase by P1-(lin-benzo-5'-adenosyl)-P4-(5'-adenosyl) tetraphosphate and P1-(lin-benzo-5'-adenosyl)-P5-(5'-adenosyl pentaphosphate. P1-(lin-Benzo-5'-adenosyl)-P5-(5'-adenosyl) penraphosphate and P1-(lin-benzo-5'-adenosyl)-P4-(5'-adenosyl) tetraphosphate have been synthesized from lin-benzoadenosine 5'-monophosphoromorpholidate and adenosine 5'-tetraphosphate and adenosine 5'-triphosphate. These mixed dinucleoside polyphosphates are potent inhibitors of porcine muscle adenylate kinase, with association constants of 2 x 10(5) M-1 for the pentaphosphate and 2 x 10(6) M-1 for the tetraphosphate, respectively, as determined by kinetics and fluorescence experiments. The increase in fluorescence intensities and fluorescence lifetimes of both inhibitors upon binding to adenylate kinase results from a breaking of the intramolecular stacking interaction observed when these ligands are free in solution and implicates their binding to the enzyme in an \"open\" or \"extended\" form. These results and the dimensional requirements of these inhibitors are discussed in relation to our current knowledge of the active site of adenylate kinase and to the known inhibitors of adenylate kinase, P1,P5-bis(5'-adenosyl) pentaphosphate and P1,P4-bis-(5'-adenosyl) tetraphosphate."}
{"id": "PMID:229899", "title": "Denaturation of thermophilic ferricytochrome c-552 by acid, guanidine hydrochloride, and heat.", "content": "The denaturation of Thermus thermophilus cytochrome c-552 by acid, guanidine hydrochloride, and heat was studied by measuring the changes in absorption and circular dichroism. Cytochrome c-552 was remarkably resistant to acid; the pK of the transition from the low- to the high-spin form was roughly 0.3. The effect of guanidine hydrochloride on the heme iron-methionine bond of Thermus and horse cytochromes c was also investigated; a comparison of the free-energy changes for the displacement of the bond indicated that the coordination in cytochrome c-552 is highly stable. The spectra of guanidine hydrochloride unfolded cytochrome c-552 were dependent on the pH; the titration curve showed the presence of a cooperative single transition of pK = 4.7, with a one-proton dissociation, suggesting the ionization of a histidine residue. In the presence of guanidine hydrochloride, the influence of the heat on the ligand bond in cytochrome c-552 was studied. The van't Hoff plots of the reaction were biphasic. The enthalpy changes in the higher temperature range were independent on the guanidine hydrochloride concentration, while those in the lower range were not.", "contents": "Denaturation of thermophilic ferricytochrome c-552 by acid, guanidine hydrochloride, and heat. The denaturation of Thermus thermophilus cytochrome c-552 by acid, guanidine hydrochloride, and heat was studied by measuring the changes in absorption and circular dichroism. Cytochrome c-552 was remarkably resistant to acid; the pK of the transition from the low- to the high-spin form was roughly 0.3. The effect of guanidine hydrochloride on the heme iron-methionine bond of Thermus and horse cytochromes c was also investigated; a comparison of the free-energy changes for the displacement of the bond indicated that the coordination in cytochrome c-552 is highly stable. The spectra of guanidine hydrochloride unfolded cytochrome c-552 were dependent on the pH; the titration curve showed the presence of a cooperative single transition of pK = 4.7, with a one-proton dissociation, suggesting the ionization of a histidine residue. In the presence of guanidine hydrochloride, the influence of the heat on the ligand bond in cytochrome c-552 was studied. The van't Hoff plots of the reaction were biphasic. The enthalpy changes in the higher temperature range were independent on the guanidine hydrochloride concentration, while those in the lower range were not."}
{"id": "PMID:229900", "title": "Binding of platinum(II) intercalation reagents to deoxyribnonucleic acid. Dependence on base-pair composition, nature of the intercalator, and ionic strength.", "content": "The DNA binding of three platinum(II) intercalation reagents has been studied and found to depend upon base composition, the nature of the intercalator, and the ionic strength of the solvent medium. In 0.2 M NaCl, binding data for calf thymus DNA show the association constants to be approximately 10(4) M-1. The binding constants decrease in the order [(o-phen)Pt(en)]2+ greater than or equal to [(terpy)Pt(HET)]+ greater than [(bipy)Pt(en)]2+. The number of available intercalation sites for the doubly charged intercalators is only 70% of the number expected from the nearest-neighbor exclusion model. Binding of [(o-phen)Pt(en)]2+ and [(terpy)Pt(HET)]+ to various DNAs depends linearly on G.C content. Both reagents exhibit essentially the same degree of G.C specificity. Intercalative binding is a function of ionic strength. Increasing the salt concentration minimizes the importance of metallointercalator charge, and extrapolation to 1 M salt reveals the intercalative abilities, as reflected in binding constants, to be equivalent for [(terpy)Pt(HET)]+ and [o-phen)Pt(en)]2+ and about 1 order of magnitude less than that of ethidium.", "contents": "Binding of platinum(II) intercalation reagents to deoxyribnonucleic acid. Dependence on base-pair composition, nature of the intercalator, and ionic strength. The DNA binding of three platinum(II) intercalation reagents has been studied and found to depend upon base composition, the nature of the intercalator, and the ionic strength of the solvent medium. In 0.2 M NaCl, binding data for calf thymus DNA show the association constants to be approximately 10(4) M-1. The binding constants decrease in the order [(o-phen)Pt(en)]2+ greater than or equal to [(terpy)Pt(HET)]+ greater than [(bipy)Pt(en)]2+. The number of available intercalation sites for the doubly charged intercalators is only 70% of the number expected from the nearest-neighbor exclusion model. Binding of [(o-phen)Pt(en)]2+ and [(terpy)Pt(HET)]+ to various DNAs depends linearly on G.C content. Both reagents exhibit essentially the same degree of G.C specificity. Intercalative binding is a function of ionic strength. Increasing the salt concentration minimizes the importance of metallointercalator charge, and extrapolation to 1 M salt reveals the intercalative abilities, as reflected in binding constants, to be equivalent for [(terpy)Pt(HET)]+ and [o-phen)Pt(en)]2+ and about 1 order of magnitude less than that of ethidium."}
{"id": "PMID:229901", "title": "Glutamyl transfer ribonucleic acid synthetase of Escherichia coli. Study of the interactions with its substrates.", "content": "The binding of the various substrates to Escherichia coli glutamyl-tRNA synthetase has been investigated by using as experimental approaches the binding study under equilibrium conditions and the substrate-induced protection of the enzyme against its thermal inactivation. The results show that ATP and tRNAGlu bind to the free enzyme, whereas glutamate binds only to an enzyme form to which glutamate-accepting tRNAGlu is associated. By use of modified E. coli tRNAsGlu and heterologous tRNAsGlu, a correlation could be established between the ability of tRNAGlu to be aminoacylated by glutamyl-tRNA synthetase and its abilities to promote the [32P]PPi-ATP isotope exchange and the binding of glutamate to the synthetase. These results give a possible explanation for the inability of blutamyl-tRNA synthetase to catalyze the isotope exchange in the absence of amino acid accepting tRNAGlu and for the failure to detect an enzyme-adenylate complex for this synthetase by using the usual approaches. One binding site was detected for each substrate. The specificity of the interaction of the various substrates has been further investigated. Concerning ATP, inhibition studies of the aminoacylation reaction by various analogues showed the existence of a synergistic effect between the adenine and the ribose residues for the interaction of adenosine. The primary recognition of ATP involves the N-1 and the 6-amino group of adenine as well as the 2'-OH group of ribose. This first interaction is then strengthened by the phosphate groups- Inhibition studies by various analogues of glutamate showed a strong decrease in the affinity of this substrate for the synthetase after substitution of the alpha- or gamma-carboxyl groups. The enzyme exhibits a marked tendency to complex tRNAs of other specificities even in the presence of tRNAGlu. MgCl2 and spermidine favor the specific interactions. The influence of monovalent ions and of pH on the interaction between glutamyl-tRNA synthetase and tRNAGlu is similar to those reported for other synthetases not requiring their cognate tRNA to bind the amino acid. Finally, contrary to that reported for other monomeric synthetases, no dimerization of glutamyl-tRNA synthetase occurs during the catalytic process.", "contents": "Glutamyl transfer ribonucleic acid synthetase of Escherichia coli. Study of the interactions with its substrates. The binding of the various substrates to Escherichia coli glutamyl-tRNA synthetase has been investigated by using as experimental approaches the binding study under equilibrium conditions and the substrate-induced protection of the enzyme against its thermal inactivation. The results show that ATP and tRNAGlu bind to the free enzyme, whereas glutamate binds only to an enzyme form to which glutamate-accepting tRNAGlu is associated. By use of modified E. coli tRNAsGlu and heterologous tRNAsGlu, a correlation could be established between the ability of tRNAGlu to be aminoacylated by glutamyl-tRNA synthetase and its abilities to promote the [32P]PPi-ATP isotope exchange and the binding of glutamate to the synthetase. These results give a possible explanation for the inability of blutamyl-tRNA synthetase to catalyze the isotope exchange in the absence of amino acid accepting tRNAGlu and for the failure to detect an enzyme-adenylate complex for this synthetase by using the usual approaches. One binding site was detected for each substrate. The specificity of the interaction of the various substrates has been further investigated. Concerning ATP, inhibition studies of the aminoacylation reaction by various analogues showed the existence of a synergistic effect between the adenine and the ribose residues for the interaction of adenosine. The primary recognition of ATP involves the N-1 and the 6-amino group of adenine as well as the 2'-OH group of ribose. This first interaction is then strengthened by the phosphate groups- Inhibition studies by various analogues of glutamate showed a strong decrease in the affinity of this substrate for the synthetase after substitution of the alpha- or gamma-carboxyl groups. The enzyme exhibits a marked tendency to complex tRNAs of other specificities even in the presence of tRNAGlu. MgCl2 and spermidine favor the specific interactions. The influence of monovalent ions and of pH on the interaction between glutamyl-tRNA synthetase and tRNAGlu is similar to those reported for other synthetases not requiring their cognate tRNA to bind the amino acid. Finally, contrary to that reported for other monomeric synthetases, no dimerization of glutamyl-tRNA synthetase occurs during the catalytic process."}
{"id": "PMID:229903", "title": "Determination of individual side-chain conformations, tertiary conformations, and molecular topography of tyrocidine A from scalar coupling constants and chemical shifts.", "content": "We report for the decapeptide tyrocidine A: (a) H alpha and H beta chemical shifts and scalar coupling constants for most residues of tyrocidine A in methanol-d4 and dimethyl-d6 sulfoxide (Me2so-d6) and the H alpha and H beta chemical shifts for other residues; (b) scalar coupling constants 3J alpha beta for nine side chains in methanol-d4 but only seven side chains in Me2SO-d6, due to chemical shift degeneracy; the Gln9 and Tyr10 side chains in methanol-d4 were only approximately analyzed; (c) a total spin-spin analysis of Pro5 in Me2SO-d6 and, partly by comparison, also in methanol-d4; (d) conversion of 3J alpha beta values to side-chain conformations for all residues in methanol-d4; comparisons, where possible, led to the conclusion that side-chain conformations are similar in methanol-d4 and Me2SO-d6; (e) an absolute conformational analysis of Pro5 from 3J values and a method of assigning all pro-R,S protons; Pro5 has a Ramachandran B, C2-Cexo-Cendo conformation; (f) chi 1, chi 2 conformations of several aromatic residues based upon proton-chromophore distance measurement from anomalous chemical shifts and Johnson-Bovey diagrams; (g) pro-R and pro-S assignments of H beta's from anomalous chemical shifts, high-temperature dependence of anomalous chemical shifts, and backbone side-chain nuclear Overhauser effects; (h) most tertiary conformations of the whole tyrocidine A molecule possessing residues 4--8 and 10 in highly preferred (ca. 90%) chi 1 conformations, but residues 1--3 and 9 having at least two chi 1 rotamers; (2) description of three topographical regions of the molecule--a hydrophobic region, a flat hydrophilic surface on the other side of the molecule, and a hydrophilic region consisting of two peptide backbone units and the side chains of Asn8, Gln9, and Tyr10; (j) proposed side chain, beta-turn, and beta-pleated sheet conformations that readily account for all \"normal\" and anomalous chemical shifts.", "contents": "Determination of individual side-chain conformations, tertiary conformations, and molecular topography of tyrocidine A from scalar coupling constants and chemical shifts. We report for the decapeptide tyrocidine A: (a) H alpha and H beta chemical shifts and scalar coupling constants for most residues of tyrocidine A in methanol-d4 and dimethyl-d6 sulfoxide (Me2so-d6) and the H alpha and H beta chemical shifts for other residues; (b) scalar coupling constants 3J alpha beta for nine side chains in methanol-d4 but only seven side chains in Me2SO-d6, due to chemical shift degeneracy; the Gln9 and Tyr10 side chains in methanol-d4 were only approximately analyzed; (c) a total spin-spin analysis of Pro5 in Me2SO-d6 and, partly by comparison, also in methanol-d4; (d) conversion of 3J alpha beta values to side-chain conformations for all residues in methanol-d4; comparisons, where possible, led to the conclusion that side-chain conformations are similar in methanol-d4 and Me2SO-d6; (e) an absolute conformational analysis of Pro5 from 3J values and a method of assigning all pro-R,S protons; Pro5 has a Ramachandran B, C2-Cexo-Cendo conformation; (f) chi 1, chi 2 conformations of several aromatic residues based upon proton-chromophore distance measurement from anomalous chemical shifts and Johnson-Bovey diagrams; (g) pro-R and pro-S assignments of H beta's from anomalous chemical shifts, high-temperature dependence of anomalous chemical shifts, and backbone side-chain nuclear Overhauser effects; (h) most tertiary conformations of the whole tyrocidine A molecule possessing residues 4--8 and 10 in highly preferred (ca. 90%) chi 1 conformations, but residues 1--3 and 9 having at least two chi 1 rotamers; (2) description of three topographical regions of the molecule--a hydrophobic region, a flat hydrophilic surface on the other side of the molecule, and a hydrophilic region consisting of two peptide backbone units and the side chains of Asn8, Gln9, and Tyr10; (j) proposed side chain, beta-turn, and beta-pleated sheet conformations that readily account for all \"normal\" and anomalous chemical shifts."}
{"id": "PMID:229906", "title": "Glucocorticoid regulation of mouse mammary tumor virus gene expression.", "content": "Glucocorticoid hormones act rapidly and specifically to stimulate the synthesis of mouse mammary tumor virus RNA in a variety of mouse mammary tumor cells and infected heterologous cells. The increase in viral RNA production appears to be mediated by receptor proteins and requires the presence of basal levels of viral RNA. Infection of heterologous cells with MMTV may alter host cell responses to glucocorticoids; in addition, production of unintegrated viral DNA in these cells has provided reagents required for studying the structure and function of the viral DNA itself. The advent of new techniques for genetic manipulation of eukaryotic cells and for isolation of large amounts of specific DNA sequences should now permit detailed analyses of steroid hormone action in this system.", "contents": "Glucocorticoid regulation of mouse mammary tumor virus gene expression. Glucocorticoid hormones act rapidly and specifically to stimulate the synthesis of mouse mammary tumor virus RNA in a variety of mouse mammary tumor cells and infected heterologous cells. The increase in viral RNA production appears to be mediated by receptor proteins and requires the presence of basal levels of viral RNA. Infection of heterologous cells with MMTV may alter host cell responses to glucocorticoids; in addition, production of unintegrated viral DNA in these cells has provided reagents required for studying the structure and function of the viral DNA itself. The advent of new techniques for genetic manipulation of eukaryotic cells and for isolation of large amounts of specific DNA sequences should now permit detailed analyses of steroid hormone action in this system."}
{"id": "PMID:229908", "title": "Oxidation of fatty alcohols to acids in the caecum of a gourami (Trichogaster cosby).", "content": "Oxidation of fatty alcohols to acids in gourami caeca was investigated by measuring the reduction of NAD+ and the formation of labeled hexadecanoic acid from [1(-14)C]hexadecanol. Virtually all dehydrogenase activity is in the microsomal fraction. Maximal activity is obtained with NAD+ as cofactor whereas with NADP+ 60% of that activity is obtained. The enzyme is rather specific for long chain alcohols and 2 NADH are formed for each molecule of hexadecanol oxidized to acid. It is stabilized by mercaptoethanol, and completely inhibited by p-chloromercuribenzoate. The activity is optimal at pH 9.5. At higher pH, small amounts of aldehyde are found. The first reaction in the sequence, fatty alcohol leads to aldehyde leads to acid seems to occur under the more physiological condition at a much slower rate than the second reaction so that free aldehyde is not detected. Addition of palmitic acid indicated an uncompetitive product inhibition. The oxidation of alcohol to acid is reversible only to a very minor extent even in the presence of NADPH, CoA, ATP and Mg2+. Location, activity and properties of the enzyme are in agreement with the earlier observation from dietary experiments that in the gourami fatty alcohols of wax esters are oxidized to acids in the course of absorption.", "contents": "Oxidation of fatty alcohols to acids in the caecum of a gourami (Trichogaster cosby). Oxidation of fatty alcohols to acids in gourami caeca was investigated by measuring the reduction of NAD+ and the formation of labeled hexadecanoic acid from [1(-14)C]hexadecanol. Virtually all dehydrogenase activity is in the microsomal fraction. Maximal activity is obtained with NAD+ as cofactor whereas with NADP+ 60% of that activity is obtained. The enzyme is rather specific for long chain alcohols and 2 NADH are formed for each molecule of hexadecanol oxidized to acid. It is stabilized by mercaptoethanol, and completely inhibited by p-chloromercuribenzoate. The activity is optimal at pH 9.5. At higher pH, small amounts of aldehyde are found. The first reaction in the sequence, fatty alcohol leads to aldehyde leads to acid seems to occur under the more physiological condition at a much slower rate than the second reaction so that free aldehyde is not detected. Addition of palmitic acid indicated an uncompetitive product inhibition. The oxidation of alcohol to acid is reversible only to a very minor extent even in the presence of NADPH, CoA, ATP and Mg2+. Location, activity and properties of the enzyme are in agreement with the earlier observation from dietary experiments that in the gourami fatty alcohols of wax esters are oxidized to acids in the course of absorption."}
{"id": "PMID:229909", "title": "A dolichyl phosphate-cleaving acid phosphatase from Tetrahymena pyriformis.", "content": "Tetrahymena pyriformis contains an enzyme which hydrolyzed dolichyl phosphate. This activity was solubilized from lyophilized samples of this organism and was relatively stable when stored frozen. The soluble enzyme preparation had an acid pH optimum and hydrolyzed both dolichyl and phytanyl phosphates at equivalent rates. The polyprenylphosphate phosphatase activity was compared with the acid phosphatases which hydrolyzed p-nitrophenyl phosphate and marked differences were found. Dolichyl phosphate hydrolysis required Mg2+ for maximum activity while the bulk of the phosphatase activity was not effected by the absence of this ion. Other differences were that the polyprenylphosphate phosphatase was relatively insensitive to inhibitors such as tartrate and vanadium oxide sulfate which had a pronounced effect on the rate of p-nitrophenyl phosphate hydrolysis. The two activities also appeared to have different subcellular distributions. The polyprenylphosphate phosphatase was markedly inhibited by ethoxy formic anhydride, a reagent which is active against enzymes containing a histidine residue at their active site, while p-nitrophenyl phosphate hydrolysis was unaffected. The polyprenylphosphate phosphatase may be important in regulating the level of dolichyl phosphate in T. pyriformis and thus the rate of glycoprotein synthesis. It is also a useful tool which is capable of liberating dolichol from dolichyl phosphate under mild conditions which will permit the further characterization of the polyprenols.", "contents": "A dolichyl phosphate-cleaving acid phosphatase from Tetrahymena pyriformis. Tetrahymena pyriformis contains an enzyme which hydrolyzed dolichyl phosphate. This activity was solubilized from lyophilized samples of this organism and was relatively stable when stored frozen. The soluble enzyme preparation had an acid pH optimum and hydrolyzed both dolichyl and phytanyl phosphates at equivalent rates. The polyprenylphosphate phosphatase activity was compared with the acid phosphatases which hydrolyzed p-nitrophenyl phosphate and marked differences were found. Dolichyl phosphate hydrolysis required Mg2+ for maximum activity while the bulk of the phosphatase activity was not effected by the absence of this ion. Other differences were that the polyprenylphosphate phosphatase was relatively insensitive to inhibitors such as tartrate and vanadium oxide sulfate which had a pronounced effect on the rate of p-nitrophenyl phosphate hydrolysis. The two activities also appeared to have different subcellular distributions. The polyprenylphosphate phosphatase was markedly inhibited by ethoxy formic anhydride, a reagent which is active against enzymes containing a histidine residue at their active site, while p-nitrophenyl phosphate hydrolysis was unaffected. The polyprenylphosphate phosphatase may be important in regulating the level of dolichyl phosphate in T. pyriformis and thus the rate of glycoprotein synthesis. It is also a useful tool which is capable of liberating dolichol from dolichyl phosphate under mild conditions which will permit the further characterization of the polyprenols."}
{"id": "PMID:229910", "title": "Guinea pig very low density lipoproteins are a good substrate for lipoprotein lipase.", "content": "In contrast to plasma from most other animals, guinea pig plasma causes little or no stimulation of lipoprotein lipase activity. Very low density lipoproteins (VLDL) isolated by ultracentrifugation of guinea pig serum caused a definite stimulation of lipase activity, whereas the infranatant inhibited the activity. Gel filtration in 5 M guanidinium hydrochloride of delipidated VLDL demonstrated that the activation was caused by a low molecular weight protein. The VLDL themselves were hydrolized at similar rates as human VLDL both by guinea pig and by bovine lipoprotein lipases. Thus, guinea pig VLDL contain an activator for lipoprotein lipase analogous to that in other animals and there is enough of the activator to support rapid hydrolysis of the VLDL lipids by the lipase.", "contents": "Guinea pig very low density lipoproteins are a good substrate for lipoprotein lipase. In contrast to plasma from most other animals, guinea pig plasma causes little or no stimulation of lipoprotein lipase activity. Very low density lipoproteins (VLDL) isolated by ultracentrifugation of guinea pig serum caused a definite stimulation of lipase activity, whereas the infranatant inhibited the activity. Gel filtration in 5 M guanidinium hydrochloride of delipidated VLDL demonstrated that the activation was caused by a low molecular weight protein. The VLDL themselves were hydrolized at similar rates as human VLDL both by guinea pig and by bovine lipoprotein lipases. Thus, guinea pig VLDL contain an activator for lipoprotein lipase analogous to that in other animals and there is enough of the activator to support rapid hydrolysis of the VLDL lipids by the lipase."}
{"id": "PMID:229911", "title": "Individual assignments of the heme resonances in the 360 MHz 1H NMR spectra of cytochrome c-557 from Crithidia oncopelti.", "content": "With the use of nuclear Overhauser effects, spin decoupling and saturation transfer experiments individual assignments for numerous resonances of the heme group in the 360 MHz 1H NMR spectra of reduced and oxidized cytochrome c-557 from Crithidia oncopelti were obtained. These data provide direct evidence that the heme substituent in position 2 is a vinyl group. They further show that in spite of the different covalent structures of the heme groups the heme crevice and the electronic heme structure in the oxidized state are nearly identical in cytochrome c-557 and in mammalian cytochromes c.", "contents": "Individual assignments of the heme resonances in the 360 MHz 1H NMR spectra of cytochrome c-557 from Crithidia oncopelti. With the use of nuclear Overhauser effects, spin decoupling and saturation transfer experiments individual assignments for numerous resonances of the heme group in the 360 MHz 1H NMR spectra of reduced and oxidized cytochrome c-557 from Crithidia oncopelti were obtained. These data provide direct evidence that the heme substituent in position 2 is a vinyl group. They further show that in spite of the different covalent structures of the heme groups the heme crevice and the electronic heme structure in the oxidized state are nearly identical in cytochrome c-557 and in mammalian cytochromes c."}
{"id": "PMID:229912", "title": "Preparation and partial characterization of iron-sulfur, iron-selenium, and iron-tellurium complexes of bovine serum albumin.", "content": "An artificial Fe-S* protein was prepared by the reaction of bovine serum albumin with FeSO4 and Na2S or with a synthetic Fe-S*-1,4-butanenedithiol complex. These improved methods enabled us to characterize the derivatives from serum albumin. The Fe-S* albumin complex has about 20 iron ions  and 14 labile sulfur atoms per molecule of the protein, whose absorption spectrum closely resembled that of 2Fe-2S* proteins. Its electron paramagnetic resonance spectrum exhibited signals different from those of ferredoxins. The addition of p-chloromercuriphenylsulfonate quenched the optical absorption in the visible region as well as the electron paramagnetic resonance signals. These properties of the albumin-iron complex are similar to those of iron-sulfur dithiothreitol and mercaptoethanol complexes, suggesting that the albumin-iron complex has one or more protein ligands besides sulfur lignads. Presumably, the oxygen atom of the tyrosine residue, or other hydroxyamino acids participates in the complex formation. In this context, the albumin polypeptide appears to be incapable of forming an iron-sulfur cluster identical to those of ferredoxins. Yet, from the albumin-iron derivative, the extrusion of the iron-sulfur core with benzenethiol provided products similar to those from ferredoxins. The iron-selenium and iron-tellurium derivatives of the bovine serum albumin were prepared and partially characterized by optical absorption and electron paramagnetic resonsnace spectroscopies. These results imply that both selenium and tellurium can be incorporated into the protein molecule as the respective labile components.", "contents": "Preparation and partial characterization of iron-sulfur, iron-selenium, and iron-tellurium complexes of bovine serum albumin. An artificial Fe-S* protein was prepared by the reaction of bovine serum albumin with FeSO4 and Na2S or with a synthetic Fe-S*-1,4-butanenedithiol complex. These improved methods enabled us to characterize the derivatives from serum albumin. The Fe-S* albumin complex has about 20 iron ions  and 14 labile sulfur atoms per molecule of the protein, whose absorption spectrum closely resembled that of 2Fe-2S* proteins. Its electron paramagnetic resonance spectrum exhibited signals different from those of ferredoxins. The addition of p-chloromercuriphenylsulfonate quenched the optical absorption in the visible region as well as the electron paramagnetic resonance signals. These properties of the albumin-iron complex are similar to those of iron-sulfur dithiothreitol and mercaptoethanol complexes, suggesting that the albumin-iron complex has one or more protein ligands besides sulfur lignads. Presumably, the oxygen atom of the tyrosine residue, or other hydroxyamino acids participates in the complex formation. In this context, the albumin polypeptide appears to be incapable of forming an iron-sulfur cluster identical to those of ferredoxins. Yet, from the albumin-iron derivative, the extrusion of the iron-sulfur core with benzenethiol provided products similar to those from ferredoxins. The iron-selenium and iron-tellurium derivatives of the bovine serum albumin were prepared and partially characterized by optical absorption and electron paramagnetic resonsnace spectroscopies. These results imply that both selenium and tellurium can be incorporated into the protein molecule as the respective labile components."}
{"id": "PMID:229913", "title": "Contractile proteins in epidermis. Isolation and properties of guinea-pig epidermal myosin.", "content": "Proteins of apparent molecular weights between 10 000 and 250 000 could be solubilized from guinea pig epidermis using a Tris/sucrose/ATP buffer. When the ionic concentration of the solubilized extract was made 75 mM with respect to KCl and 2 mM with respect to MgCl2, a protein complex precipitated which on SDS-polyacrylamide gel electrophoresis resolved into bands corresponding in migration to myosin, actin and a number of low molecular weight proteins. Myosin was dissociated from the complex with 0.6 M KI and purified by gel filtration chromatography on an agarose column. The purified epidermal myosin fraction contained a polypeptide of 200 000 molecular weight andtwo low molecular weight polypeptides of 16 500 and 13 000. The amino acid composition of the epidermal myosin heavy chain was similar to that of muscle myosin. At high ionic strength epidermal myosin had high specific (K+ + Ca2+)- and (K+ + EDTA)-ATPase activities and low specific (K+ + Mg2+)-ATPase activity. The pH activity curves of the (K+ + Ca2+)- and (K+ + EDTA)-ATPase were different. ATP was hydrolyzed faster than other nucleoside triphosphates. At low ionic strength, the (K+ + Mg2+)-ATPase activity of epidermal myosin was stimulated two fold by skeletal muscle actin. The myosin formed bipolar filaments in 50 mM KCl in the presence of 5 mM Mg2+.", "contents": "Contractile proteins in epidermis. Isolation and properties of guinea-pig epidermal myosin. Proteins of apparent molecular weights between 10 000 and 250 000 could be solubilized from guinea pig epidermis using a Tris/sucrose/ATP buffer. When the ionic concentration of the solubilized extract was made 75 mM with respect to KCl and 2 mM with respect to MgCl2, a protein complex precipitated which on SDS-polyacrylamide gel electrophoresis resolved into bands corresponding in migration to myosin, actin and a number of low molecular weight proteins. Myosin was dissociated from the complex with 0.6 M KI and purified by gel filtration chromatography on an agarose column. The purified epidermal myosin fraction contained a polypeptide of 200 000 molecular weight andtwo low molecular weight polypeptides of 16 500 and 13 000. The amino acid composition of the epidermal myosin heavy chain was similar to that of muscle myosin. At high ionic strength epidermal myosin had high specific (K+ + Ca2+)- and (K+ + EDTA)-ATPase activities and low specific (K+ + Mg2+)-ATPase activity. The pH activity curves of the (K+ + Ca2+)- and (K+ + EDTA)-ATPase were different. ATP was hydrolyzed faster than other nucleoside triphosphates. At low ionic strength, the (K+ + Mg2+)-ATPase activity of epidermal myosin was stimulated two fold by skeletal muscle actin. The myosin formed bipolar filaments in 50 mM KCl in the presence of 5 mM Mg2+."}
{"id": "PMID:229914", "title": "Interaction of cytochrome c with the phosphorprotein phosvitin.", "content": "Candida krusei cytochrome c forms a molecular complex with phosphorprotein phosvitin in weakly alkaline solution of low ionic strength. At most, about 22 molecules of cytochrome c bind to a phosvitin molecule. The complex at the binding ratio below about 11 (half of the maximum ratio) as a much higher binding strength. Several lines of evidence indicate that the marked difference in the binding strength is due to the difference in negative charges on phosvitin molecule concerned in the binding of a cytochrome c molecule. The phosvitin-bound cytochrome c seems to have a preferred orientation with the front surface of the molecule containing the exposed heme edge in contact with the phosvitin molecule.", "contents": "Interaction of cytochrome c with the phosphorprotein phosvitin. Candida krusei cytochrome c forms a molecular complex with phosphorprotein phosvitin in weakly alkaline solution of low ionic strength. At most, about 22 molecules of cytochrome c bind to a phosvitin molecule. The complex at the binding ratio below about 11 (half of the maximum ratio) as a much higher binding strength. Several lines of evidence indicate that the marked difference in the binding strength is due to the difference in negative charges on phosvitin molecule concerned in the binding of a cytochrome c molecule. The phosvitin-bound cytochrome c seems to have a preferred orientation with the front surface of the molecule containing the exposed heme edge in contact with the phosvitin molecule."}
{"id": "PMID:229915", "title": "Heme-linked properties of Pseudomonas cytochrome c peroxidase. Evidence for non-equivalence of the hemes.", "content": "Pseudomonas cytochrome c peroxidase contains two hemes, one of which is shown to be in low-spin and one in high-spin state. The ferric enzyme reveals absorption maxima at 640 and 705 nm. The alkaline transition of these bands indicates the sixth iron-binding ligand of the low-spin and high-spin heme to be, respectively, a methionyl residue and a water molecule. The high-spin heme reacts with hydrogen peroxide to form a ferryl structure, which is the reactive intermediate in the peroxidatic reaction. The ferrous enzyme binds carbon monoxide in a 1:1 molar ratio, whereas the ferric form is unreactive towards small anionic ligands like F- and CN-. On this basis the peroxidase may also be classified as a cytochrome cc'.", "contents": "Heme-linked properties of Pseudomonas cytochrome c peroxidase. Evidence for non-equivalence of the hemes. Pseudomonas cytochrome c peroxidase contains two hemes, one of which is shown to be in low-spin and one in high-spin state. The ferric enzyme reveals absorption maxima at 640 and 705 nm. The alkaline transition of these bands indicates the sixth iron-binding ligand of the low-spin and high-spin heme to be, respectively, a methionyl residue and a water molecule. The high-spin heme reacts with hydrogen peroxide to form a ferryl structure, which is the reactive intermediate in the peroxidatic reaction. The ferrous enzyme binds carbon monoxide in a 1:1 molar ratio, whereas the ferric form is unreactive towards small anionic ligands like F- and CN-. On this basis the peroxidase may also be classified as a cytochrome cc'."}
{"id": "PMID:229916", "title": "On the evolution of blue proteins.", "content": "Amino acid sequences of 8 plastocyanins, 8 azurins, stellacyanin, two regions in human ceruloplasmin (ferroxidase)--all of which proteins are known to bind a blue (type 1) copper--and subunit II of bovine mitochondrial cytochrome c oxidase were compared by statistical methods to assess similarities and derive possible evolutionary relationships. It is suggested that all of the examined proteins are monophyletic. The two ceruloplasmin partial sequences clearly demonstrate that this protein has undergone a duplication. A calculated most parcimonious phylogenetic tree shows the divergence of the azurin and plastocyanin ancestor to be the earliest event. Stellacyanin and later the blue oxidase (ceruloplasmin) evolved from the plastocyanin branch, which the cytochrome c oxidase subunit evolved from the azurin ancestor.", "contents": "On the evolution of blue proteins. Amino acid sequences of 8 plastocyanins, 8 azurins, stellacyanin, two regions in human ceruloplasmin (ferroxidase)--all of which proteins are known to bind a blue (type 1) copper--and subunit II of bovine mitochondrial cytochrome c oxidase were compared by statistical methods to assess similarities and derive possible evolutionary relationships. It is suggested that all of the examined proteins are monophyletic. The two ceruloplasmin partial sequences clearly demonstrate that this protein has undergone a duplication. A calculated most parcimonious phylogenetic tree shows the divergence of the azurin and plastocyanin ancestor to be the earliest event. Stellacyanin and later the blue oxidase (ceruloplasmin) evolved from the plastocyanin branch, which the cytochrome c oxidase subunit evolved from the azurin ancestor."}
{"id": "PMID:229924", "title": "[Reinnervation mechanism of skeletal muscles damaged by botulism toxin].", "content": "Reinnervation by botulinus toxin impaired motor nerve implantation was investigated in rat experiments with a purpose of elucidating conditions for regeneration of nerve fibers in the area of botulinic paralysis. Administration of the sublethal dose of toxin into the limb accelerated synaptogenesis of the nerve implanted. The latter exerts a normalizing effect on the muscular tissue and polarization level of its fibers.", "contents": "[Reinnervation mechanism of skeletal muscles damaged by botulism toxin]. Reinnervation by botulinus toxin impaired motor nerve implantation was investigated in rat experiments with a purpose of elucidating conditions for regeneration of nerve fibers in the area of botulinic paralysis. Administration of the sublethal dose of toxin into the limb accelerated synaptogenesis of the nerve implanted. The latter exerts a normalizing effect on the muscular tissue and polarization level of its fibers."}
{"id": "PMID:229925", "title": "[Effect of diazepam on the Na, K-ATPase state in a penicillin--induced hyperactivity focus in the cerebral cortex].", "content": "Intramuscular injection of diazepam to rats at doses of 0.01 and 2 mg/kg 25-30 min after penicillin application to the rat brain cortex leads to alteration of periodic appearance of epileptic seizures (ES), to changes in the seizure pattern, and to emergence of periodic acceleration of epileptiform discharges (ED). Injection of diazepam at a dose of 2 mg/kg 20 min before penicillin application results in the reduction of ED latency in the epileptogenic focus and in a decrease in their frequency before seizures as compared to the control animals without diazepam injection. ES appear irregularly, their quantity is markedly reduced while duration is increased. Diazepam injection leads to disappearance of the rat moving reaction during ER and ES. In vivo experiments diazepam (2 mg/kg) does not influence brain cortex Na, K-ATPase of crude synaptosomes. However, diazepam leads to an increase in Na, K-ATPase activity both in the primary and dependent secondary epileptogenic foci. It is suggested that the anticonvulsant action of diazepam may be underlain by its activating effect on Na, K-ATPase of neuronal membranes in the epileptogenic focus.", "contents": "[Effect of diazepam on the Na, K-ATPase state in a penicillin--induced hyperactivity focus in the cerebral cortex]. Intramuscular injection of diazepam to rats at doses of 0.01 and 2 mg/kg 25-30 min after penicillin application to the rat brain cortex leads to alteration of periodic appearance of epileptic seizures (ES), to changes in the seizure pattern, and to emergence of periodic acceleration of epileptiform discharges (ED). Injection of diazepam at a dose of 2 mg/kg 20 min before penicillin application results in the reduction of ED latency in the epileptogenic focus and in a decrease in their frequency before seizures as compared to the control animals without diazepam injection. ES appear irregularly, their quantity is markedly reduced while duration is increased. Diazepam injection leads to disappearance of the rat moving reaction during ER and ES. In vivo experiments diazepam (2 mg/kg) does not influence brain cortex Na, K-ATPase of crude synaptosomes. However, diazepam leads to an increase in Na, K-ATPase activity both in the primary and dependent secondary epileptogenic foci. It is suggested that the anticonvulsant action of diazepam may be underlain by its activating effect on Na, K-ATPase of neuronal membranes in the epileptogenic focus."}
{"id": "PMID:229926", "title": "[Significance of beta-adrenoreception in realizing the glycogenolytic and lipolytic effects of excess thyroid hormones].", "content": "In experiments on rats the chronic administration of beta-adrenoblocker obsidan (propranolol) in doses blocking the glycogenolytic and lipolytic effects of exogenous epinephrine does not prevent a decrease in the liver and heart glycogen level and an increase of free fatty acids (FFA) in the serum as well as of lipolytic activity of adipose tissue in vitro, which are produced by high doses of thyroxine.", "contents": "[Significance of beta-adrenoreception in realizing the glycogenolytic and lipolytic effects of excess thyroid hormones]. In experiments on rats the chronic administration of beta-adrenoblocker obsidan (propranolol) in doses blocking the glycogenolytic and lipolytic effects of exogenous epinephrine does not prevent a decrease in the liver and heart glycogen level and an increase of free fatty acids (FFA) in the serum as well as of lipolytic activity of adipose tissue in vitro, which are produced by high doses of thyroxine."}
{"id": "PMID:229927", "title": "[Approximately hourly rhythm of 3',5'-cAMP in rat parotid gland slices].", "content": "3',5'-CAMP concentration in rat parotid gland slices indubated in vitro for 12-14 hours was measured by radioimmunoassay. Clices for determination of cyclic nucleotide concentrations were taken at 10-minute intervals over a period of 2 hours. All slices used in a specific experiment originated from a single gland. Rhythmic changes in 3',5'-cAMP concentration in the rat parotid gland were found. The period of these changes (20-50 min) was similar to that of fluctuations in other parameters, such as dry weight, the rate of protein synthesis and ornithine decarboxylase activity, described for the same system elsewhere.", "contents": "[Approximately hourly rhythm of 3',5'-cAMP in rat parotid gland slices]. 3',5'-CAMP concentration in rat parotid gland slices indubated in vitro for 12-14 hours was measured by radioimmunoassay. Clices for determination of cyclic nucleotide concentrations were taken at 10-minute intervals over a period of 2 hours. All slices used in a specific experiment originated from a single gland. Rhythmic changes in 3',5'-cAMP concentration in the rat parotid gland were found. The period of these changes (20-50 min) was similar to that of fluctuations in other parameters, such as dry weight, the rate of protein synthesis and ornithine decarboxylase activity, described for the same system elsewhere."}
{"id": "PMID:229928", "title": "[Microionophoretic study of interaction of cyclic purine nucleotides and mediator substances on the cortical neurons].", "content": "Statistically significant data indicating selective interaction of noradenaline and cAMP as well as of acetylcholine and cGMP were obtained in experiments on the microionophoretic bringing of cyclic purine nucleotides and mediator substances acetylcholine and noradrenaline to the rabbit cortical neurons. Studies on the relationships between cAMP and cGMP at the single unit level suggest their multilevel functional interaction with other systems of intracellular regulators.", "contents": "[Microionophoretic study of interaction of cyclic purine nucleotides and mediator substances on the cortical neurons]. Statistically significant data indicating selective interaction of noradenaline and cAMP as well as of acetylcholine and cGMP were obtained in experiments on the microionophoretic bringing of cyclic purine nucleotides and mediator substances acetylcholine and noradrenaline to the rabbit cortical neurons. Studies on the relationships between cAMP and cGMP at the single unit level suggest their multilevel functional interaction with other systems of intracellular regulators."}
{"id": "PMID:229929", "title": "[Antistress effects of diazepam and activation of the positive reinforcing system upon changes on corticosteroid excretion and lipid level after peripheral electric pain stimulation].", "content": "It was shown in experiments on rats that the reaction of self-stimulation (SS) decreased the enhanced level of 11-hydrohycorticosteroids (11-HCS) in the blood after electrical pain stimulation(EPS) of the feet. Diazepam (1 mg/kg) decreased the levels of 11-HCS and beta-lipoproteids and increased the level of phospholipids after self-stimulation and pain stimulation. Diazepam and preliminary electrical pain stimulation induced activation of self-stimulation. It is concluded that diazepam and the activation of the positive reinforcing system exert similar effects on 11-HCS excretion and lipid levels after pain stimulation.", "contents": "[Antistress effects of diazepam and activation of the positive reinforcing system upon changes on corticosteroid excretion and lipid level after peripheral electric pain stimulation]. It was shown in experiments on rats that the reaction of self-stimulation (SS) decreased the enhanced level of 11-hydrohycorticosteroids (11-HCS) in the blood after electrical pain stimulation(EPS) of the feet. Diazepam (1 mg/kg) decreased the levels of 11-HCS and beta-lipoproteids and increased the level of phospholipids after self-stimulation and pain stimulation. Diazepam and preliminary electrical pain stimulation induced activation of self-stimulation. It is concluded that diazepam and the activation of the positive reinforcing system exert similar effects on 11-HCS excretion and lipid levels after pain stimulation."}
{"id": "PMID:229930", "title": "[Effect of obsidan on some mechanisms of the heart productivity regulation].", "content": "In acute experiments on anesthetized cats obsidan caused a decrease in the venous blood inflow to the heart and increased the volume of the vascular bed. It is suggested that the blockade of the myocardial beta-adrenoreceptors is not the only cause of such an effect.", "contents": "[Effect of obsidan on some mechanisms of the heart productivity regulation]. In acute experiments on anesthetized cats obsidan caused a decrease in the venous blood inflow to the heart and increased the volume of the vascular bed. It is suggested that the blockade of the myocardial beta-adrenoreceptors is not the only cause of such an effect."}
{"id": "PMID:229931", "title": "[Multiphasic regulatory system mediating the effect of estradiol in rat uterus].", "content": "Estradiol is shown to induce histidine decarboxylase and histamine to activate adenylate cyclase in the rat uterus. Cyclic AMP like histamine simulates the effect of estradiol, intensifying RNA synthesis and inducing glycolytic enzymes and uterus inhibition. It was found by autoradiography that 3H-estradiol is accepted by the nuclei of some myometrium cells, 3H-histamine by their cytoplasm and 3H-cAMP is selectively bound by endothelium cells of the uterus capillaries. The estradiol messengers (histamine and cAMP) seem to mediate hormonal effect of some uterus heterofunctional cells forming a kind of multicellular functional system.", "contents": "[Multiphasic regulatory system mediating the effect of estradiol in rat uterus]. Estradiol is shown to induce histidine decarboxylase and histamine to activate adenylate cyclase in the rat uterus. Cyclic AMP like histamine simulates the effect of estradiol, intensifying RNA synthesis and inducing glycolytic enzymes and uterus inhibition. It was found by autoradiography that 3H-estradiol is accepted by the nuclei of some myometrium cells, 3H-histamine by their cytoplasm and 3H-cAMP is selectively bound by endothelium cells of the uterus capillaries. The estradiol messengers (histamine and cAMP) seem to mediate hormonal effect of some uterus heterofunctional cells forming a kind of multicellular functional system."}
{"id": "PMID:229935", "title": "Effects of the histamine H2-receptor blocking drugs burimamide and cimetidine on noradrenergic transmission in the isolated aorta of the rabbit and atria of the guinea-pig.", "content": "1 In rabbit aortic strips, concentration-response curves to noradrenaline (NA) were shifted to the right in a parallel and concentration-dependent manner by the alpha-adrenoceptor blocking drug, phentolamine and also by the histamine H(2)-receptor blocking drugs, burimamide and cimetidine. Responses to 5-hydroxytryptamine were not affected by these drugs.2 Burimamide had the properties of a competitive antagonist of noradrenaline, possessing about one-hundredth the potency of phentolamine. Cimetidine was weaker than burimamide and did not fulfil the requirements for competitive antagonism of noradrenaline.3 In guinea-pig isolated atria, in which noradrenergic transmitter stores were labelled with [(3)H]-noradrenaline, phentolamine (3 muM), burimamide (30 muM) and cimetidine (30 muM), in decreasing order of effectiveness, each enhanced stimulation-induced efflux of [(3)H]-noradrenaline, indicating that their blocking effects on prejunctional alpha-adrenoceptors in this tissue are in the same order of relative potency as on postjunctional alpha-adrenoceptors in rabbit aortic strips.4 In the concentrations used (30 muM), neither burimamide nor cimetidine interfered with the neuronal uptake of noradrenaline. Burimamide, and to a much lesser extent, cimetidine, increased the resting efflux of [(3)H]-noradrenaline from guinea-pig atria.5 The effect of clonidine, a partial agonist on prejunctional alpha-adrenoceptors in guinea-pig atria, in increasing stimulation-induced efflux of [(3)H]-noradrenaline when stimulated with 150 pulses at 5 Hz was blocked by cimetidine (30 muM) and reversed by phentolamine (3 muM) and burimamide (30 muM).", "contents": "Effects of the histamine H2-receptor blocking drugs burimamide and cimetidine on noradrenergic transmission in the isolated aorta of the rabbit and atria of the guinea-pig. 1 In rabbit aortic strips, concentration-response curves to noradrenaline (NA) were shifted to the right in a parallel and concentration-dependent manner by the alpha-adrenoceptor blocking drug, phentolamine and also by the histamine H(2)-receptor blocking drugs, burimamide and cimetidine. Responses to 5-hydroxytryptamine were not affected by these drugs.2 Burimamide had the properties of a competitive antagonist of noradrenaline, possessing about one-hundredth the potency of phentolamine. Cimetidine was weaker than burimamide and did not fulfil the requirements for competitive antagonism of noradrenaline.3 In guinea-pig isolated atria, in which noradrenergic transmitter stores were labelled with [(3)H]-noradrenaline, phentolamine (3 muM), burimamide (30 muM) and cimetidine (30 muM), in decreasing order of effectiveness, each enhanced stimulation-induced efflux of [(3)H]-noradrenaline, indicating that their blocking effects on prejunctional alpha-adrenoceptors in this tissue are in the same order of relative potency as on postjunctional alpha-adrenoceptors in rabbit aortic strips.4 In the concentrations used (30 muM), neither burimamide nor cimetidine interfered with the neuronal uptake of noradrenaline. Burimamide, and to a much lesser extent, cimetidine, increased the resting efflux of [(3)H]-noradrenaline from guinea-pig atria.5 The effect of clonidine, a partial agonist on prejunctional alpha-adrenoceptors in guinea-pig atria, in increasing stimulation-induced efflux of [(3)H]-noradrenaline when stimulated with 150 pulses at 5 Hz was blocked by cimetidine (30 muM) and reversed by phentolamine (3 muM) and burimamide (30 muM)."}
{"id": "PMID:229938", "title": "Colonic carcinoma at the site of ureterosigmoidostomy: what is the risk?", "content": "A case of colonic carcinoma arising 27 years after urinary diversion by ureterosigmoidostomy is reported. This late complication is now well recognized and increasing numbers of cases are being reported. The implications of this patient and the 31 previously reported cases are considered.", "contents": "Colonic carcinoma at the site of ureterosigmoidostomy: what is the risk? A case of colonic carcinoma arising 27 years after urinary diversion by ureterosigmoidostomy is reported. This late complication is now well recognized and increasing numbers of cases are being reported. The implications of this patient and the 31 previously reported cases are considered."}
{"id": "PMID:229939", "title": "Granular cell myoblastoma of the breast: a report of 2 cases.", "content": "Two cases of granular cell myoblastoma of the breast are presented occurring in women aged 20 and 22 years. The clinical findings, mammographic and naked eye appearances suggested carcinoma. The difficulties of diagnosis and the pathogenesis of this rare tumour are discussed. A definitive histological diagnosis of an apparently malignant breast lump, particularly in a young woman, is mandatory before proceeding to major surgery.", "contents": "Granular cell myoblastoma of the breast: a report of 2 cases. Two cases of granular cell myoblastoma of the breast are presented occurring in women aged 20 and 22 years. The clinical findings, mammographic and naked eye appearances suggested carcinoma. The difficulties of diagnosis and the pathogenesis of this rare tumour are discussed. A definitive histological diagnosis of an apparently malignant breast lump, particularly in a young woman, is mandatory before proceeding to major surgery."}
{"id": "PMID:229941", "title": "Essential hypertension: effect of an oral inhibitor of angiotensin-converting enzyme.", "content": "Captopril, a specific oral inhibitor of angiotensin-converting enzyme, was given to 18 unselected patients with moderate essential hypertension. Mean blood pressure fell by 14.5% at the maximum dose given, and this fall was significantly correlated with the initial plasma renin activity. The main fall in blood pressure occurred two hours after the first dose of captopril. These results suggest that captopril effectively lowers blood pressure in patients with essential hypertension and that the renin-angiotensin aldosterone system may maintain blood pressure in essential hypertension. This does not necessarily imply that the renin-angiotensin system is the cause of the high blood pressure.", "contents": "Essential hypertension: effect of an oral inhibitor of angiotensin-converting enzyme. Captopril, a specific oral inhibitor of angiotensin-converting enzyme, was given to 18 unselected patients with moderate essential hypertension. Mean blood pressure fell by 14.5% at the maximum dose given, and this fall was significantly correlated with the initial plasma renin activity. The main fall in blood pressure occurred two hours after the first dose of captopril. These results suggest that captopril effectively lowers blood pressure in patients with essential hypertension and that the renin-angiotensin aldosterone system may maintain blood pressure in essential hypertension. This does not necessarily imply that the renin-angiotensin system is the cause of the high blood pressure."}
{"id": "PMID:229944", "title": "Diabetic impotence: studies of nocturnal erection during REM sleep.", "content": "Nocturnal erections were studied in 30 diabetic patients who complained of impotence and in 11 healthy volunteers. The maximum increase in penile circumference was measured by a penile strain-gauge and recorded on a portable tape-recorder; an external oculogram was recorded simultaneously to identify periods of rapid-eye-movement sleep. The technique gave reproducible results, was acceptable to patients, and was suitable for use in an oridnary hospital ward. Only six diabetics showed a maximum increase in penile circumference of under 15 mm, whereas all but one of the healthy subjects showed maximum increases above this value. Of the six diabetics, five complained of total impotence and had other features of autonomic neuropathy that suggested an organic basis for their impotence. The other patient complained of partial importence, which was probably caused by psychological factors. These findings suggest that the prevalence of organic impotence among diabetics has been overestimated.", "contents": "Diabetic impotence: studies of nocturnal erection during REM sleep. Nocturnal erections were studied in 30 diabetic patients who complained of impotence and in 11 healthy volunteers. The maximum increase in penile circumference was measured by a penile strain-gauge and recorded on a portable tape-recorder; an external oculogram was recorded simultaneously to identify periods of rapid-eye-movement sleep. The technique gave reproducible results, was acceptable to patients, and was suitable for use in an oridnary hospital ward. Only six diabetics showed a maximum increase in penile circumference of under 15 mm, whereas all but one of the healthy subjects showed maximum increases above this value. Of the six diabetics, five complained of total impotence and had other features of autonomic neuropathy that suggested an organic basis for their impotence. The other patient complained of partial importence, which was probably caused by psychological factors. These findings suggest that the prevalence of organic impotence among diabetics has been overestimated."}
{"id": "PMID:229945", "title": "[Existence of \"endorphin cells\" in the adenohypophysis of the cat; comparison with \"corticotropin cells.\" Immunocytochemical study].", "content": "Indirect immunofluorescence technique with anti-17-39ACTH and anti beta-endorphin sera has allowed us to detect \"corticotropic cells\" in the anterior and intermediate lobes of the adenohypophysis of the male cat. The corticotropic cells of the anterior lobe are localized in the median zone; they are PAS-positive and appeared intensively coloured in dark blue with the Herlant's tetrachrome. All the cells of the intermediate lobe react with the anti-17-39ACTH serum. Using an anti-beta-endorphin serum, we have observed that all the corticotropic cells of the anterior lobe react; but in the intermediate lobe, only a part of \"corticotropic cells\" react with the anti-beta-endorphin serum.", "contents": "[Existence of \"endorphin cells\" in the adenohypophysis of the cat; comparison with \"corticotropin cells.\" Immunocytochemical study]. Indirect immunofluorescence technique with anti-17-39ACTH and anti beta-endorphin sera has allowed us to detect \"corticotropic cells\" in the anterior and intermediate lobes of the adenohypophysis of the male cat. The corticotropic cells of the anterior lobe are localized in the median zone; they are PAS-positive and appeared intensively coloured in dark blue with the Herlant's tetrachrome. All the cells of the intermediate lobe react with the anti-17-39ACTH serum. Using an anti-beta-endorphin serum, we have observed that all the corticotropic cells of the anterior lobe react; but in the intermediate lobe, only a part of \"corticotropic cells\" react with the anti-beta-endorphin serum."}
{"id": "PMID:229947", "title": "Failure to reverse cholera toxin induced intestinal secretion by agents which decrease mucosal cAMP.", "content": "The feasibility of reducing intestinal secretion by the use of agents which decrease intestinal mucosal cAMP concentration has been investigated in the weanling pig and the rabbit. Three different agents for decreasing mucosal cAMP concentration were studied. The cyclic nucleotide phosphodiesterase activator, imidazole, significantly reduced mucosal cAMP concentrations only in the weanling pig. Intraluminal 2'-deoxyadenosine-3'AMP inhibited adenylate cyclase and caused a decrease in mucosal cAMP concentration in both the pig and the rabbit. The introduction of the heat-stable enterotoxin of Escherichia coli into pig jejunal segments also gave lowered mucosal cAMP concentrations. While these three agents effectively reduced cAMP concentrations in intestinal mucosa, they were ineffective in reducing the net fluid secretory effects of cholera toxin. Secretion caused by cholera toxin apparently persists independent of the temporary changes in cAMP concentration which can be induced by pharmacological agents.", "contents": "Failure to reverse cholera toxin induced intestinal secretion by agents which decrease mucosal cAMP. The feasibility of reducing intestinal secretion by the use of agents which decrease intestinal mucosal cAMP concentration has been investigated in the weanling pig and the rabbit. Three different agents for decreasing mucosal cAMP concentration were studied. The cyclic nucleotide phosphodiesterase activator, imidazole, significantly reduced mucosal cAMP concentrations only in the weanling pig. Intraluminal 2'-deoxyadenosine-3'AMP inhibited adenylate cyclase and caused a decrease in mucosal cAMP concentration in both the pig and the rabbit. The introduction of the heat-stable enterotoxin of Escherichia coli into pig jejunal segments also gave lowered mucosal cAMP concentrations. While these three agents effectively reduced cAMP concentrations in intestinal mucosa, they were ineffective in reducing the net fluid secretory effects of cholera toxin. Secretion caused by cholera toxin apparently persists independent of the temporary changes in cAMP concentration which can be induced by pharmacological agents."}
{"id": "PMID:229948", "title": "Distribution and metabolism of adrenocorticotropin in the rat.", "content": "The time course of plasma bioactive adrenocorticotropin (ACTH) concentrations measured following two rapid injections of the hormone at doses of 7.5 and 22.5 mU/100 g, iv, and one infusion over a period of 80 min at a rate of 1.3 mU/min per 100 g, to male Sprague-Dawley rats whose endogenous release of ACTH had been blocked, leads to the conclusion that the hormone is distributed in two compartments. Indeed, the rapid fall of plasma ACTH concentrations in the early minutes following either the injections or the stop of the infusion is followed by a much slower phase. There is no significant difference between the measurements and the two-compartment model outputs. The model represents, on the average, the mean values of the measurements plus or minus 1 standard error for the single injections and plus or minus 1.2 standard error for the infusion.", "contents": "Distribution and metabolism of adrenocorticotropin in the rat. The time course of plasma bioactive adrenocorticotropin (ACTH) concentrations measured following two rapid injections of the hormone at doses of 7.5 and 22.5 mU/100 g, iv, and one infusion over a period of 80 min at a rate of 1.3 mU/min per 100 g, to male Sprague-Dawley rats whose endogenous release of ACTH had been blocked, leads to the conclusion that the hormone is distributed in two compartments. Indeed, the rapid fall of plasma ACTH concentrations in the early minutes following either the injections or the stop of the infusion is followed by a much slower phase. There is no significant difference between the measurements and the two-compartment model outputs. The model represents, on the average, the mean values of the measurements plus or minus 1 standard error for the single injections and plus or minus 1.2 standard error for the infusion."}
{"id": "PMID:229949", "title": "Neural activation of alpha-adrenoreceptors in glucose mobilization from liver.", "content": "Using a newly described method for obtaining pure, mixed hepatic venous blood samples, it was demonstrated that glucose mobilization from the liver of the anesthetized cat in response to hepatic nerve stimulation is via alpha-adrenergic receptors. Neither the elevation of portal pressure nor the amount of glucose generated by the liver was affected by intraportal administration of 1 mg propranolol/kg (beta blockade). In the presence of alpha-receptor blockade (3 mg phentolamine/kg) the portal venous pressure change was minor and the glucose output actually decreased slightly upon nerve stimulation, a response consistent with our previously demonstrated reduction of glucose output by parasympathetic nerve stimulation. The present responses to nerve stimulation were not due to activation of pancreatic nerves since these nerves were routinely ligated.", "contents": "Neural activation of alpha-adrenoreceptors in glucose mobilization from liver. Using a newly described method for obtaining pure, mixed hepatic venous blood samples, it was demonstrated that glucose mobilization from the liver of the anesthetized cat in response to hepatic nerve stimulation is via alpha-adrenergic receptors. Neither the elevation of portal pressure nor the amount of glucose generated by the liver was affected by intraportal administration of 1 mg propranolol/kg (beta blockade). In the presence of alpha-receptor blockade (3 mg phentolamine/kg) the portal venous pressure change was minor and the glucose output actually decreased slightly upon nerve stimulation, a response consistent with our previously demonstrated reduction of glucose output by parasympathetic nerve stimulation. The present responses to nerve stimulation were not due to activation of pancreatic nerves since these nerves were routinely ligated."}
{"id": "PMID:229951", "title": "Pitfalls in the diagnosis of leg pain.", "content": "Problems may confront the practitioner in the diagnosis of leg pain related to exercise. The diagnostic features of the history and the physical examination that will help to elucidate the various causes of leg pain are outlined in this article, and the necessity for re-examination of the patient after a period of exercise is stressed. In most patients the diagnosis can most easily be made by means of clinical methods, without recourse to special investigations.", "contents": "Pitfalls in the diagnosis of leg pain. Problems may confront the practitioner in the diagnosis of leg pain related to exercise. The diagnostic features of the history and the physical examination that will help to elucidate the various causes of leg pain are outlined in this article, and the necessity for re-examination of the patient after a period of exercise is stressed. In most patients the diagnosis can most easily be made by means of clinical methods, without recourse to special investigations."}
{"id": "PMID:229955", "title": "Topography of somatostatin cells in the stomach of the rat: possible functional significance.", "content": "Somatostatin cells in the stomach of the rat have a characteristic shape and distribution. In the antral mucosa they occur together with gastrin cells and enterochromaffin cells at the base of the glands. In the oxyntic mucosa they are scattered along the entire glands with some predominance in the zone of parietal cells. Throughout the gastric mucosa the somatostatin cells possess long and slender processes that emerge from the base of the cell and end in club-like swellings. Such processes appear to contact a certain proportion of neighbouring gastrin cells in the antral mucosa and parietal cells in the oxyntic mucosa. Exogenous somatostatin given by intravenous infusion to conscious rats counteracted the release of gastrin stimulated by feeding, elevated antral pH or vagal excitation. Gastrin causes parietal cells to secrete HCl and endocrine cells in the oxyntic mucosa to mobilise and synthesise histamine. Somatostatin is known to block the respone of the parietal cells to gastrin. In contrast, somatostatin did not block the response of the histamine-storing endocrine cells to gastrin, perhaps because these endocrine cells lack receptors to somatostatin. Conceivably, somatostatin in the gastric mucosa has a paracrine mode of action. The observations of the present study suggest that somatostatin may affect some, but not all of the various cell types in the stomach. Under physiological conditions this selectivity may be achieved in the following ways: 1) Communication may be based on direct cell-to-cell contact. 2) Only certain cell types are supplied with somatostatin receptors.", "contents": "Topography of somatostatin cells in the stomach of the rat: possible functional significance. Somatostatin cells in the stomach of the rat have a characteristic shape and distribution. In the antral mucosa they occur together with gastrin cells and enterochromaffin cells at the base of the glands. In the oxyntic mucosa they are scattered along the entire glands with some predominance in the zone of parietal cells. Throughout the gastric mucosa the somatostatin cells possess long and slender processes that emerge from the base of the cell and end in club-like swellings. Such processes appear to contact a certain proportion of neighbouring gastrin cells in the antral mucosa and parietal cells in the oxyntic mucosa. Exogenous somatostatin given by intravenous infusion to conscious rats counteracted the release of gastrin stimulated by feeding, elevated antral pH or vagal excitation. Gastrin causes parietal cells to secrete HCl and endocrine cells in the oxyntic mucosa to mobilise and synthesise histamine. Somatostatin is known to block the respone of the parietal cells to gastrin. In contrast, somatostatin did not block the response of the histamine-storing endocrine cells to gastrin, perhaps because these endocrine cells lack receptors to somatostatin. Conceivably, somatostatin in the gastric mucosa has a paracrine mode of action. The observations of the present study suggest that somatostatin may affect some, but not all of the various cell types in the stomach. Under physiological conditions this selectivity may be achieved in the following ways: 1) Communication may be based on direct cell-to-cell contact. 2) Only certain cell types are supplied with somatostatin receptors."}
{"id": "PMID:229956", "title": "ACTH-like immunoreactivity in two electronically coupled giant neurons in the pond snail Lymnaea stagnalis.", "content": "Two giant neurons (diameter 130 micron) were identified immunocytochemically by means of the unlabeled antibody enzyme technique with anti-ACTH 1-39 and 1-24 in the pond snail Lymnaea stagnalis. The cells are located in the visceral and the right parietal ganglion, respectively. They contain moderately electron dense elementary granules (diameter 150-160 nm). By means of the intracellular horseradish peroxidase injection technique it was shown that the cells send fibres into the neuropiles of various ganglia and into nerves. Synapses occur on the fine fibre branches in the neuropile. Synapse-like structures were found on the cell bodies and on the major fibres. The giant neurons are electrotonically coupled. With toluidine blue staining for small peptides it was demonstrated that in the central nervous system of the pond snail numerous peptidergic neurons occur in addition to those identified with the classical staining methods for neurosecretion.", "contents": "ACTH-like immunoreactivity in two electronically coupled giant neurons in the pond snail Lymnaea stagnalis. Two giant neurons (diameter 130 micron) were identified immunocytochemically by means of the unlabeled antibody enzyme technique with anti-ACTH 1-39 and 1-24 in the pond snail Lymnaea stagnalis. The cells are located in the visceral and the right parietal ganglion, respectively. They contain moderately electron dense elementary granules (diameter 150-160 nm). By means of the intracellular horseradish peroxidase injection technique it was shown that the cells send fibres into the neuropiles of various ganglia and into nerves. Synapses occur on the fine fibre branches in the neuropile. Synapse-like structures were found on the cell bodies and on the major fibres. The giant neurons are electrotonically coupled. With toluidine blue staining for small peptides it was demonstrated that in the central nervous system of the pond snail numerous peptidergic neurons occur in addition to those identified with the classical staining methods for neurosecretion."}
{"id": "PMID:229957", "title": "Morphological changes of pituitary gonadotrophs and thyrotrophs following treatment with LH-RH or TRH in vitro.", "content": "To investigate the relationship between LH-RH and TRH and the formation of castration cells and thyroidectomy cells, pituitary glands of 14-day old female rats were cultured with LH-RH or TRH for 10 days. Observed in these glands were external and internal zones, the former containing active, healthy appearing cells, and the latter consisting of many degenerative and necrotic cells. Gonadotrophs and thyrotrophs were readily demonstrated in the external zone of the organs by immunocytochemistry. Hypertrophic gonadotrophs (castration cells) and thyrotrophs (thyroidectomy cells) were observed only in the external zone by electron microscopy. Neither the typical signet-ring gonadotrophs nor intracisternal granules of thyroidectomy cells were seen in the present study. However, the hypertrophic gonadotrophs or thyrotrophs were similar to castration cells or thyroidectomy cells observed in the pituitary gland following castration or thyroidectomy. The results indicate that LH-RH and TRH directly stimulate the secretion of hormones and alter the morphological features of pituitary target cells.", "contents": "Morphological changes of pituitary gonadotrophs and thyrotrophs following treatment with LH-RH or TRH in vitro. To investigate the relationship between LH-RH and TRH and the formation of castration cells and thyroidectomy cells, pituitary glands of 14-day old female rats were cultured with LH-RH or TRH for 10 days. Observed in these glands were external and internal zones, the former containing active, healthy appearing cells, and the latter consisting of many degenerative and necrotic cells. Gonadotrophs and thyrotrophs were readily demonstrated in the external zone of the organs by immunocytochemistry. Hypertrophic gonadotrophs (castration cells) and thyrotrophs (thyroidectomy cells) were observed only in the external zone by electron microscopy. Neither the typical signet-ring gonadotrophs nor intracisternal granules of thyroidectomy cells were seen in the present study. However, the hypertrophic gonadotrophs or thyrotrophs were similar to castration cells or thyroidectomy cells observed in the pituitary gland following castration or thyroidectomy. The results indicate that LH-RH and TRH directly stimulate the secretion of hormones and alter the morphological features of pituitary target cells."}
{"id": "PMID:229959", "title": "Stability of the \"two active X\" phenotype in triploid somatic cells.", "content": "We examined triploid cells of XXY karyotype heterozygous for glucose 6 phosphate dehydrogenase (G6PD) electrophoretic variants with regard to the stability of their X chromosome phenotype. Clonal populations of cells derived from these human fibroblasts maintained a precise 1:2:1 ratio of A:heteropolymer:B isozymes throughout their life span, indicating stability of the two active X chromosomes in these cells. To determine the influence of the autosomal complement on X chromosome expression, we attempted to perturb the relationship. Fusion of these triploid cells with human diploid fibroblasts carrying a novel G6PD variant (B') resulted in heterokaryons exprssing a novel heteropolymer, presumably indicating that all three parental X chromosomes were active. However, no derepression of the inactive X chromosome was observed. Analysis of interspecific hybrids derived from triploid cells and mouse fibroblasts confirmed that activity of parental X chromosomes is maintained. Some human mouse hybrid clones, however, expressed only a single human G6PD isozyme, probably attributable to segregation of the pertinent X chromosome, but elimination of a relevant autosome cannot be excluded. The triploid cells transformed by SV40 showed alterations in LDH pattern and an approximately 10-20% decrease in chromosome number, but maintained the precise G6PD phenotype of the untransformed cell. These studies provide evidence for the stability of the X chromosome phenotype in triploid cells.", "contents": "Stability of the \"two active X\" phenotype in triploid somatic cells. We examined triploid cells of XXY karyotype heterozygous for glucose 6 phosphate dehydrogenase (G6PD) electrophoretic variants with regard to the stability of their X chromosome phenotype. Clonal populations of cells derived from these human fibroblasts maintained a precise 1:2:1 ratio of A:heteropolymer:B isozymes throughout their life span, indicating stability of the two active X chromosomes in these cells. To determine the influence of the autosomal complement on X chromosome expression, we attempted to perturb the relationship. Fusion of these triploid cells with human diploid fibroblasts carrying a novel G6PD variant (B') resulted in heterokaryons exprssing a novel heteropolymer, presumably indicating that all three parental X chromosomes were active. However, no derepression of the inactive X chromosome was observed. Analysis of interspecific hybrids derived from triploid cells and mouse fibroblasts confirmed that activity of parental X chromosomes is maintained. Some human mouse hybrid clones, however, expressed only a single human G6PD isozyme, probably attributable to segregation of the pertinent X chromosome, but elimination of a relevant autosome cannot be excluded. The triploid cells transformed by SV40 showed alterations in LDH pattern and an approximately 10-20% decrease in chromosome number, but maintained the precise G6PD phenotype of the untransformed cell. These studies provide evidence for the stability of the X chromosome phenotype in triploid cells."}
{"id": "PMID:229958", "title": "Immunoreactivity for beta-endorphin in LH-RH neurons of the fetal human hypothalamus.", "content": "A peptide immunochemically related to beta-endorphin was detected in some LH-RH neurons of the fetal human hypothalamus by comparison of adjacent sections stained for beta-endorphin and for LH-RH. In the same section, by successive staining and after antibody elution, both peptides were again revealed in the same neuron. The significance of the presence of the beta-endorphin-like material in LH-RH neurons is discussed.", "contents": "Immunoreactivity for beta-endorphin in LH-RH neurons of the fetal human hypothalamus. A peptide immunochemically related to beta-endorphin was detected in some LH-RH neurons of the fetal human hypothalamus by comparison of adjacent sections stained for beta-endorphin and for LH-RH. In the same section, by successive staining and after antibody elution, both peptides were again revealed in the same neuron. The significance of the presence of the beta-endorphin-like material in LH-RH neurons is discussed."}
{"id": "PMID:229960", "title": "Regulation of the microtubule steady state in vitro by ATP.", "content": "ATP increases microtubule steady state assembly and disassembly rates in vitro in a concentration-dependent manner. Bovine brain microtubules, composed of 75% tubulin and 25% high molecular weight microtubule-associated proteins (MAPs), were purified by three cycles of assembly and disassembly in the absence of ATP. When assembled to steady state, these microtubules add dimers at one end and lose them at the other in a unidirectional assembly-disassembly process. In the presence of 1.0 mM ATP the unidirectional flow of tubulin from one end of the microtubules to the other increases as much as 20 fold, as revealed by loss of 3H-GTP from uniformly labeled microtubules under GTP chase conditions and by the rate of disassembly following addition of 50 microM podophyllotoxin. UTP, CTP and 5' adenylylimidodiphosphate (AMP-PNP) cannot substitute for ATP in producing this effect. Furthermore, the increase in steady state flow rate persists afer ATP is removed. Thus microtubules assembled in ATP and centrifuged through sucrose cushions to separate them from nucleotides continue to exhibit increased rates in the next assembly cycle in the absence of ATP. It is possible that an ATP-dependent microtubule protein kinase is responsible for the observed increase in tubulin flow rate. A kinase activity associated with brain MAPs has been reported to be cAMP-dependent (Sloboda et al., 1975). We have found an adenylate cyclase activity associated with these microtubules. Whether the adenylate cyclase is a contaminant or due to a specific microtubules-associated protein, and whether its activity is functionally linked to the increased rate of assembly and disassembly in the presence of ATP, remain to be determined.", "contents": "Regulation of the microtubule steady state in vitro by ATP. ATP increases microtubule steady state assembly and disassembly rates in vitro in a concentration-dependent manner. Bovine brain microtubules, composed of 75% tubulin and 25% high molecular weight microtubule-associated proteins (MAPs), were purified by three cycles of assembly and disassembly in the absence of ATP. When assembled to steady state, these microtubules add dimers at one end and lose them at the other in a unidirectional assembly-disassembly process. In the presence of 1.0 mM ATP the unidirectional flow of tubulin from one end of the microtubules to the other increases as much as 20 fold, as revealed by loss of 3H-GTP from uniformly labeled microtubules under GTP chase conditions and by the rate of disassembly following addition of 50 microM podophyllotoxin. UTP, CTP and 5' adenylylimidodiphosphate (AMP-PNP) cannot substitute for ATP in producing this effect. Furthermore, the increase in steady state flow rate persists afer ATP is removed. Thus microtubules assembled in ATP and centrifuged through sucrose cushions to separate them from nucleotides continue to exhibit increased rates in the next assembly cycle in the absence of ATP. It is possible that an ATP-dependent microtubule protein kinase is responsible for the observed increase in tubulin flow rate. A kinase activity associated with brain MAPs has been reported to be cAMP-dependent (Sloboda et al., 1975). We have found an adenylate cyclase activity associated with these microtubules. Whether the adenylate cyclase is a contaminant or due to a specific microtubules-associated protein, and whether its activity is functionally linked to the increased rate of assembly and disassembly in the presence of ATP, remain to be determined."}
{"id": "PMID:229961", "title": "Two-dimensional gel analysis of cyclic AMP effects in cultured S49 mouse lymphoma cells: protein modifications, inductions and repressions.", "content": "In this study, we used two-dimensional gel electrophoresis to analyze the responses of cultured S49 mouse lymphoma cells to incubation with analogs or inducers of cyclic AMP (cAMP). Putative phosphorylations were detected by charge alterations in proteins labeled with 35S--methionine and, in some cases, confirmed by labeling with 32P--phosphate. We assessed the relative stabilities of proteins affected by cAMP, the periods of susceptibility of proteins to cAMP-dependent modification and any cAMP-mediated changes in protein synthesis or stability. Five proteins (of about 650 resolved) behave as expected for \"orthodox\" substrates of a cAMP-activated protein kinase: both newly synthesized and prelabeled forms of these proteins are subject to modification; this modification involves an acidic charge shift of about one unit; and cAMP-mediated conversion of these proteins to their modified forms is virtually complete. The acidic forms of at least three of these proteins also exhibit cAMP-mediated increases in 32P--phosphate incorporation. Each protein comprised less than approximately 0.005% of cellular protein. Under basal conditions they appear to be phosphorylated to an extent about 20--30% of that found in fully stimulated cells. Nine proteins show cAMP-dependent changes in rates of synthesis with six inductions and three repressions. Most of these changes are of a magnitude of about 3 to 5 fold, and reach their maximal extents after about 4--5 hr of exposure to dibutyryl cAMP. In addition to the phosphorylations, inductions and repressions mentioned above, approximately 12 other reproducible cAMP-dependent changes in protein patterns are observed. Mutant cell lines deficient in catalytic activity of cAMP-dependent protein kinase show none of the changes in protein pattern attributable to cAMP.", "contents": "Two-dimensional gel analysis of cyclic AMP effects in cultured S49 mouse lymphoma cells: protein modifications, inductions and repressions. In this study, we used two-dimensional gel electrophoresis to analyze the responses of cultured S49 mouse lymphoma cells to incubation with analogs or inducers of cyclic AMP (cAMP). Putative phosphorylations were detected by charge alterations in proteins labeled with 35S--methionine and, in some cases, confirmed by labeling with 32P--phosphate. We assessed the relative stabilities of proteins affected by cAMP, the periods of susceptibility of proteins to cAMP-dependent modification and any cAMP-mediated changes in protein synthesis or stability. Five proteins (of about 650 resolved) behave as expected for \"orthodox\" substrates of a cAMP-activated protein kinase: both newly synthesized and prelabeled forms of these proteins are subject to modification; this modification involves an acidic charge shift of about one unit; and cAMP-mediated conversion of these proteins to their modified forms is virtually complete. The acidic forms of at least three of these proteins also exhibit cAMP-mediated increases in 32P--phosphate incorporation. Each protein comprised less than approximately 0.005% of cellular protein. Under basal conditions they appear to be phosphorylated to an extent about 20--30% of that found in fully stimulated cells. Nine proteins show cAMP-dependent changes in rates of synthesis with six inductions and three repressions. Most of these changes are of a magnitude of about 3 to 5 fold, and reach their maximal extents after about 4--5 hr of exposure to dibutyryl cAMP. In addition to the phosphorylations, inductions and repressions mentioned above, approximately 12 other reproducible cAMP-dependent changes in protein patterns are observed. Mutant cell lines deficient in catalytic activity of cAMP-dependent protein kinase show none of the changes in protein pattern attributable to cAMP."}
{"id": "PMID:229962", "title": "Plus and minus strand leader RNAs in negative strand virus-infected cells.", "content": "Sendai virus and VSV minus strand genome RNAs, labeled specifically at their 3' ends with RNA ligase, were used as probes to detect leader RNA--that is, short transcripts (approximately 50 nucleotides) complementary to the exact 3' end of the minus strand genome. These probes have allowed the detection of plus strand leader RNAs in both Sendai virus and VSV-infected cells as well as in the virion transcriptase reactions. The use of a similar probe, prepared from the self-complementary ends of DI genome RNA and containing the 3' end of the plus strand antigenome RNA, has allowed the detection of a minus strand leader RNA of identical size in VSV-infected cells. Since the presence of DI genomes could not be detected by analytical sucrose gradient centrifugation in these VSV-infected cells, this minus strand leader RNA is apparently synthesized on the template formed by the exact 3' end of the antigenome RNA.", "contents": "Plus and minus strand leader RNAs in negative strand virus-infected cells. Sendai virus and VSV minus strand genome RNAs, labeled specifically at their 3' ends with RNA ligase, were used as probes to detect leader RNA--that is, short transcripts (approximately 50 nucleotides) complementary to the exact 3' end of the minus strand genome. These probes have allowed the detection of plus strand leader RNAs in both Sendai virus and VSV-infected cells as well as in the virion transcriptase reactions. The use of a similar probe, prepared from the self-complementary ends of DI genome RNA and containing the 3' end of the plus strand antigenome RNA, has allowed the detection of a minus strand leader RNA of identical size in VSV-infected cells. Since the presence of DI genomes could not be detected by analytical sucrose gradient centrifugation in these VSV-infected cells, this minus strand leader RNA is apparently synthesized on the template formed by the exact 3' end of the antigenome RNA."}
{"id": "PMID:229964", "title": "Characterization of a new isolate of poliovirus defective interfering particles.", "content": "An independent isolate of poliovirus defective interfering particles has been analyzed. These particles, designated DI(A), are apparently analogous to the DI particles described by Baltimore and co-investigators. Electron microscopic heteroduplex analysis reveals that the DI(A) isolate is a mixture of deletion mutants which changes with passage level. The DI(A) population consists of at least five distinct deletion mutants, including one double deletion. Electron microscopic mapping of the deleted regions indicates that most, if not all, of the viral capsid region can be deleted. Despite this heterogeneity, the mutant genomes are quite similar in physical size. We propose a model which suggests that the observed properties of poliovirus DI genomes reflect selective pressures extant during the amplification of the mutant genome. According to this model, only those deleted genomes which retain a minimal size and the capacity to synthesize a functional viral polymerase will replicate successfully in a mixed infection. Furthermore, this model proposes a mechanism for the enrichment of poliovirus DI genomes and an explanation for the low level of complementation observed in mixed infections of picornaviruses.", "contents": "Characterization of a new isolate of poliovirus defective interfering particles. An independent isolate of poliovirus defective interfering particles has been analyzed. These particles, designated DI(A), are apparently analogous to the DI particles described by Baltimore and co-investigators. Electron microscopic heteroduplex analysis reveals that the DI(A) isolate is a mixture of deletion mutants which changes with passage level. The DI(A) population consists of at least five distinct deletion mutants, including one double deletion. Electron microscopic mapping of the deleted regions indicates that most, if not all, of the viral capsid region can be deleted. Despite this heterogeneity, the mutant genomes are quite similar in physical size. We propose a model which suggests that the observed properties of poliovirus DI genomes reflect selective pressures extant during the amplification of the mutant genome. According to this model, only those deleted genomes which retain a minimal size and the capacity to synthesize a functional viral polymerase will replicate successfully in a mixed infection. Furthermore, this model proposes a mechanism for the enrichment of poliovirus DI genomes and an explanation for the low level of complementation observed in mixed infections of picornaviruses."}
{"id": "PMID:229967", "title": "Differences between the endogenous and exogenous DNA sequences of Rous-associated virus-O.", "content": "DNA sequences related to the endogenous retrovirus of chickens, Rous-associated virus-O (RAV-O), have been examined using site-specific DNA endonuclease analysis of cellular DNA derived from line 15 and line 100 chickens. Individual embryos from both inbred lines were used as a source of embryonic fibroblasts from which cellular DNA was isolated. Analysis of DNA containing either endogenous RAV-O sequences alone or both endogenous and exogenous RAV-O sequences produced identical patterns of RAV-O-specific DNA fragments after digestion with the endonucleases Eco RI, Hind III, BgI II, Bam HI or Xho I. Similar analysis with endonucleases Hinc II or Hha I, however, produced several RAV-O-specific DNA fragments which were derived from cellular DNA containing both endogenous and exogenous RAV-O sequences but not from cellular DNA containing only endogenous sequences. Although some differences exist between the DNA fragments specific for the endogenous viral sequences of line 15 and line 100 cellular DNA, the DNA fragments specific for the exogenous viral sequences were identical between the two inbred lines. Cleavage of an unintegrated linear RAV-O DNA molecule with Hinc II or Hha I produced DNA fragments identical to those specific for the exogenously acquired RAV-O provirus. This suggests that these characteristic fragments contain no cellular DNA. The potential DNA junction fragments containing both viral and cellular DNA, identified after analysis of DNA that contains both endogenous and exogenous viral sequences, were identical to those observed after analysis of DNA containing only endogenous viral sequences. These results support the following conclusions. First, exogenous proviral sequences are integrated into chicken cell DNA following an interaction between viral and cellular DNA that is specific with respect to the virus and nonspecific with respect to the cell. Second, both the free linear RAV-O DNA intermediate and the newly integrated exogenous provirus contain specific endonuclease sites that are not found in endogenous RAV-O DNA sequences. These results suggest that the formation of the exogenous DNA provirus involves specific alteration of the endogenous viral DNA sequences before reinsertion of the sequences as the exogenous RAV-O DNA provirus. It is possible that newly integrated exogenous RAV-O sequences are characterized by specific differences in the pattern of base methylation and a limited sequence arrangement.", "contents": "Differences between the endogenous and exogenous DNA sequences of Rous-associated virus-O. DNA sequences related to the endogenous retrovirus of chickens, Rous-associated virus-O (RAV-O), have been examined using site-specific DNA endonuclease analysis of cellular DNA derived from line 15 and line 100 chickens. Individual embryos from both inbred lines were used as a source of embryonic fibroblasts from which cellular DNA was isolated. Analysis of DNA containing either endogenous RAV-O sequences alone or both endogenous and exogenous RAV-O sequences produced identical patterns of RAV-O-specific DNA fragments after digestion with the endonucleases Eco RI, Hind III, BgI II, Bam HI or Xho I. Similar analysis with endonucleases Hinc II or Hha I, however, produced several RAV-O-specific DNA fragments which were derived from cellular DNA containing both endogenous and exogenous RAV-O sequences but not from cellular DNA containing only endogenous sequences. Although some differences exist between the DNA fragments specific for the endogenous viral sequences of line 15 and line 100 cellular DNA, the DNA fragments specific for the exogenous viral sequences were identical between the two inbred lines. Cleavage of an unintegrated linear RAV-O DNA molecule with Hinc II or Hha I produced DNA fragments identical to those specific for the exogenously acquired RAV-O provirus. This suggests that these characteristic fragments contain no cellular DNA. The potential DNA junction fragments containing both viral and cellular DNA, identified after analysis of DNA that contains both endogenous and exogenous viral sequences, were identical to those observed after analysis of DNA containing only endogenous viral sequences. These results support the following conclusions. First, exogenous proviral sequences are integrated into chicken cell DNA following an interaction between viral and cellular DNA that is specific with respect to the virus and nonspecific with respect to the cell. Second, both the free linear RAV-O DNA intermediate and the newly integrated exogenous provirus contain specific endonuclease sites that are not found in endogenous RAV-O DNA sequences. These results suggest that the formation of the exogenous DNA provirus involves specific alteration of the endogenous viral DNA sequences before reinsertion of the sequences as the exogenous RAV-O DNA provirus. It is possible that newly integrated exogenous RAV-O sequences are characterized by specific differences in the pattern of base methylation and a limited sequence arrangement."}
{"id": "PMID:229968", "title": "Stimulation of collagenase production by collagen in mammalian cell cultures.", "content": "In this study, we investigated the possible regulatory role of collagen in collagenase production by cultured human skin fibroblasts and human and rabbit synovial cells. Addition of types I, II or III collagen in solution to the culture media markedly stimulated trypsin-activable collagenase activity in these cultures. In the human cell cultures the stimulatory effect of collagen was further enhanced by a soluble factor isolated from human monocyte culture media (Dayer, Russell and Krane, 1977). Both native and denatured forms of collagen stimulated enzyme production; their relative efficacy varied among the different types. The native form of both types I and II collagen showed a greater effect on collagenase production than the corresponding denatured form, whereas with type III collagen the denatured form was more effective.", "contents": "Stimulation of collagenase production by collagen in mammalian cell cultures. In this study, we investigated the possible regulatory role of collagen in collagenase production by cultured human skin fibroblasts and human and rabbit synovial cells. Addition of types I, II or III collagen in solution to the culture media markedly stimulated trypsin-activable collagenase activity in these cultures. In the human cell cultures the stimulatory effect of collagen was further enhanced by a soluble factor isolated from human monocyte culture media (Dayer, Russell and Krane, 1977). Both native and denatured forms of collagen stimulated enzyme production; their relative efficacy varied among the different types. The native form of both types I and II collagen showed a greater effect on collagenase production than the corresponding denatured form, whereas with type III collagen the denatured form was more effective."}
{"id": "PMID:229970", "title": "Pleiotropic mutations within two yeast mitochondrial cytochrome genes block mRNA processing.", "content": "The mRNAs from two yeast mitochondrial genes cob-box (cytochrome b) and oxi-3 (cytochrome oxidase 40,000 dalton subunit) are processed from large (7-10 kb) precursors. Certain mutations in each gene block the maturation of the RNAs from both genes at a variety of specific steps. The pleiotropic cytochrome b mutants seem to lack a functional trans-acting RNA required for the processing of both messengers. In contrast, the oxi-3 mutants may act by producing an activity that inhibits specific steps.", "contents": "Pleiotropic mutations within two yeast mitochondrial cytochrome genes block mRNA processing. The mRNAs from two yeast mitochondrial genes cob-box (cytochrome b) and oxi-3 (cytochrome oxidase 40,000 dalton subunit) are processed from large (7-10 kb) precursors. Certain mutations in each gene block the maturation of the RNAs from both genes at a variety of specific steps. The pleiotropic cytochrome b mutants seem to lack a functional trans-acting RNA required for the processing of both messengers. In contrast, the oxi-3 mutants may act by producing an activity that inhibits specific steps."}
{"id": "PMID:229971", "title": "Splicing and the formation of stable RNA.", "content": "To determine whether RNA splicing plays an obligatory role in gene expression, we have constructed a series of SV40-transducing viruses carrying various combinations of splice junctions derived from the viral genome and a mouse globin gene. All of the viruses that retain at least one functional splice junction, derived from either the viral or the mouse genome, encode stable hybrid RNAs. In contrast, a virus from which all the splice junctions have been removed fails to produce any detectable stable RNA. These results suggest that splicing is a prerequisite for stable RNA formation.", "contents": "Splicing and the formation of stable RNA. To determine whether RNA splicing plays an obligatory role in gene expression, we have constructed a series of SV40-transducing viruses carrying various combinations of splice junctions derived from the viral genome and a mouse globin gene. All of the viruses that retain at least one functional splice junction, derived from either the viral or the mouse genome, encode stable hybrid RNAs. In contrast, a virus from which all the splice junctions have been removed fails to produce any detectable stable RNA. These results suggest that splicing is a prerequisite for stable RNA formation."}
{"id": "PMID:229973", "title": "An activity phosphorylating tyrosine in polyoma T antigen immunoprecipitates.", "content": "Polyoma T antigen immunoprecipitates contain a protein kinase-like activity which preferentially phosphorylates material of 50-60,000 daltons molecular weight. Phosphorylation is not diminished in extracts of polyoma tsA mutant-infected cells shifted to the nonpermissive temperature late in infection, conditions which inactivate the large T antigen. Phosphorylation is reduced or absent in cells infected with polyoma host range nontransforming (hr-t) mutants, which have defective small and medium T antigens. The major acceptor of phosphate is not the heavy chain of immunoglobulin, but appears to be the polyoma medium T antigen. The large T antigen is also phosphorylated, but usually to a lower specific activity. In terms of acid and alkali sensitivity and electrophoretic and chromatographic mobility in one and two dimensions, the phosphorylated residue behaves identically to phosphotyrosine and differently than phosphorylated serine, threonine, lysine and histidine.", "contents": "An activity phosphorylating tyrosine in polyoma T antigen immunoprecipitates. Polyoma T antigen immunoprecipitates contain a protein kinase-like activity which preferentially phosphorylates material of 50-60,000 daltons molecular weight. Phosphorylation is not diminished in extracts of polyoma tsA mutant-infected cells shifted to the nonpermissive temperature late in infection, conditions which inactivate the large T antigen. Phosphorylation is reduced or absent in cells infected with polyoma host range nontransforming (hr-t) mutants, which have defective small and medium T antigens. The major acceptor of phosphate is not the heavy chain of immunoglobulin, but appears to be the polyoma medium T antigen. The large T antigen is also phosphorylated, but usually to a lower specific activity. In terms of acid and alkali sensitivity and electrophoretic and chromatographic mobility in one and two dimensions, the phosphorylated residue behaves identically to phosphotyrosine and differently than phosphorylated serine, threonine, lysine and histidine."}
{"id": "PMID:229974", "title": "Phosphorylation of polyoma T antigens.", "content": "The T antigens of polyoma virus have been examined for phosphorylation in vivo and associated protein kinase activities in vitro. The 100K \"large\" T antigen is the major phosphoprotein among the T antigen species in vivo as determined by labeling virus-infected cells with 32P-orthophosphate. Hr-t mutants show normal phosphorylation of their 100K T antigens. The wild-type 56K plasma membrane-associated \"middle\" T antigen is also phosphorylated in the cell, but to a lesser extent than the 100K; this low level phosphorylation is also observed in the presumably altered 56K protein induced by hr-t mutant NG59 and in the 50K truncated \"middle\" T of hr-t mutant SD15. Addition of dibutyryl cyclic AMP to the medium does not affect labeling of either large or middle T antigens in wild-type- or mutant-infected cells. Thus no differences are observed in T antigen phosphorylation in vivo between wild-type virus and hr-t mutants. Hr-t mutants are defective in a protein kinase activity assayed in vitro by adding gamma-32P-ATP to T antigen immunoprecipitates. In the case of wild-type virus, the 56K protein is the major phosphate acceptor in the in vitro kinase reaction, with a somewhat lower level of phosphorylation observed in the 100K band. Hr-t mutants NG59 and SD15 show no labeling of the altered 56K or 50K, respectively, but do show detectable levels of 32P in the 100K bands. A wild-type virus carrying a small deletion affecting the 100K and 56k bands shows a normal level of kinase activity associated with the truncated T antigens. Ts-a mutants appear to be normal with respect to the middle T antigen-associated kinase. Photoaffinity labeling of infected cell extracts with 8-azido cyclic AMP shows that the two major classes of regulatory subunits of cyclic AMP-dependent protein kinases are present in the immunoprecipitates. Phosphorylation of histone H1 occurs when this substrate is added to immunoprecipitates of either mock-infected or virus-infected cells, again demonstrating the presence of cellular kinases. Further experiments will be required to determine whether the middle T antigen of polyoma virus is itself a protein kinase or simply a substrate for one or more cellular kinases.", "contents": "Phosphorylation of polyoma T antigens. The T antigens of polyoma virus have been examined for phosphorylation in vivo and associated protein kinase activities in vitro. The 100K \"large\" T antigen is the major phosphoprotein among the T antigen species in vivo as determined by labeling virus-infected cells with 32P-orthophosphate. Hr-t mutants show normal phosphorylation of their 100K T antigens. The wild-type 56K plasma membrane-associated \"middle\" T antigen is also phosphorylated in the cell, but to a lesser extent than the 100K; this low level phosphorylation is also observed in the presumably altered 56K protein induced by hr-t mutant NG59 and in the 50K truncated \"middle\" T of hr-t mutant SD15. Addition of dibutyryl cyclic AMP to the medium does not affect labeling of either large or middle T antigens in wild-type- or mutant-infected cells. Thus no differences are observed in T antigen phosphorylation in vivo between wild-type virus and hr-t mutants. Hr-t mutants are defective in a protein kinase activity assayed in vitro by adding gamma-32P-ATP to T antigen immunoprecipitates. In the case of wild-type virus, the 56K protein is the major phosphate acceptor in the in vitro kinase reaction, with a somewhat lower level of phosphorylation observed in the 100K band. Hr-t mutants NG59 and SD15 show no labeling of the altered 56K or 50K, respectively, but do show detectable levels of 32P in the 100K bands. A wild-type virus carrying a small deletion affecting the 100K and 56k bands shows a normal level of kinase activity associated with the truncated T antigens. Ts-a mutants appear to be normal with respect to the middle T antigen-associated kinase. Photoaffinity labeling of infected cell extracts with 8-azido cyclic AMP shows that the two major classes of regulatory subunits of cyclic AMP-dependent protein kinases are present in the immunoprecipitates. Phosphorylation of histone H1 occurs when this substrate is added to immunoprecipitates of either mock-infected or virus-infected cells, again demonstrating the presence of cellular kinases. Further experiments will be required to determine whether the middle T antigen of polyoma virus is itself a protein kinase or simply a substrate for one or more cellular kinases."}
{"id": "PMID:229975", "title": "Structure of the Abelson murine leukemia virus genome.", "content": "Virions produced from cells transformed by A-MuLV contain a 30S, 5.6 kb RNA that can be translated in a cell-free system to form the characteristic A-MuLV protein. This RNA was mapped by heteroduplex methods using DNA probes from M-MuLV, the presumed parent of A-MuLV. The overall organization of the RNA was determined by using full-length M-MuLV reverse transcribed DNA and visualizing the heteroduplexes in the electron microscope. This showed that A-MuLV and M-MuLV have homologous sequences at both ends of their RNAs but that the central portion of the A-MuLV genome is not homologous to sequences in M-MuLV RNA. A precise measure of the lengths of the shared regions was obtained by using S1 nuclease to digest hybrids between 32P-labeled M-MuLV DNA and A-MuLV RNA; the resulting fragments were analyzed for their length by electrophoresis. The regions of homology were shown to be 1320 nucleotides long at the 5' end and 730 nucleotides long at the 3' end. Thus approximately 6200 nucleotides of the approximately 8300 in M-MuLV RNA were deleted when the A-MuLV genome was formed, but an insert of 3600 nucleotides, presumably derived from the normal murine genome, was inserted in place of the deleted region.", "contents": "Structure of the Abelson murine leukemia virus genome. Virions produced from cells transformed by A-MuLV contain a 30S, 5.6 kb RNA that can be translated in a cell-free system to form the characteristic A-MuLV protein. This RNA was mapped by heteroduplex methods using DNA probes from M-MuLV, the presumed parent of A-MuLV. The overall organization of the RNA was determined by using full-length M-MuLV reverse transcribed DNA and visualizing the heteroduplexes in the electron microscope. This showed that A-MuLV and M-MuLV have homologous sequences at both ends of their RNAs but that the central portion of the A-MuLV genome is not homologous to sequences in M-MuLV RNA. A precise measure of the lengths of the shared regions was obtained by using S1 nuclease to digest hybrids between 32P-labeled M-MuLV DNA and A-MuLV RNA; the resulting fragments were analyzed for their length by electrophoresis. The regions of homology were shown to be 1320 nucleotides long at the 5' end and 730 nucleotides long at the 3' end. Thus approximately 6200 nucleotides of the approximately 8300 in M-MuLV RNA were deleted when the A-MuLV genome was formed, but an insert of 3600 nucleotides, presumably derived from the normal murine genome, was inserted in place of the deleted region."}
{"id": "PMID:229976", "title": "The genome of human papovavirus BKV.", "content": "The complete DNA sequence of human papovavirus BKV(Dun), consisting of 5153 nucleotide pairs, is presented. We describe the segments of the genome which correspond to the replication origin, the tandem repeated sequences, the 5' and 3' ends of the mRNAs, the splice sites, the early and late viral proteins and the putative viral polypeptides. These BKV DNA sequences are compared with analogous regions in the SV40 and Py virus genomes in an attempt to localize viral functions for lytic growth and transformation.", "contents": "The genome of human papovavirus BKV. The complete DNA sequence of human papovavirus BKV(Dun), consisting of 5153 nucleotide pairs, is presented. We describe the segments of the genome which correspond to the replication origin, the tandem repeated sequences, the 5' and 3' ends of the mRNAs, the splice sites, the early and late viral proteins and the putative viral polypeptides. These BKV DNA sequences are compared with analogous regions in the SV40 and Py virus genomes in an attempt to localize viral functions for lytic growth and transformation."}
{"id": "PMID:229977", "title": "Changes in cyclic AMP binding and protein kinase activities during growth and differentiation of Blastocladiella emersonii.", "content": "Multiple protein kinases in the water mould Blastocladiella emersonii are described. A cyclic AMP-independent protein kinase which prefentially phosphorylates casein remains unchanged during vegetative growth of the cells and in the two phases of differentiation: germination and sporulation. In contrast, cyclic AMP-dependent protein kinase activity and cyclic AMP binding components are induced during the sporulation.", "contents": "Changes in cyclic AMP binding and protein kinase activities during growth and differentiation of Blastocladiella emersonii. Multiple protein kinases in the water mould Blastocladiella emersonii are described. A cyclic AMP-independent protein kinase which prefentially phosphorylates casein remains unchanged during vegetative growth of the cells and in the two phases of differentiation: germination and sporulation. In contrast, cyclic AMP-dependent protein kinase activity and cyclic AMP binding components are induced during the sporulation."}
{"id": "PMID:229979", "title": "An example of how patient selection can influence survival in glioblastoma multiforme.", "content": "Drawing on experience in evaluating postsurgical treatment of glioblastoma multiforme, it is concluded that results of clinical trials programs can be greatly affected by the status of patients who are selected for study. Investigations report results only on patients considered \"evaluable,\" a portion of the total which may be less than 20%. Improvement in patient survival should not be conceived to be due to aggressive treatment unless patient selection has been accounted for.", "contents": "An example of how patient selection can influence survival in glioblastoma multiforme. Drawing on experience in evaluating postsurgical treatment of glioblastoma multiforme, it is concluded that results of clinical trials programs can be greatly affected by the status of patients who are selected for study. Investigations report results only on patients considered \"evaluable,\" a portion of the total which may be less than 20%. Improvement in patient survival should not be conceived to be due to aggressive treatment unless patient selection has been accounted for."}
{"id": "PMID:229980", "title": "Intrapulmonary metastases from bronchogenic carcinoma and their radiographic detection.", "content": "Autopsies on 102 patients dying with bronchogenic carcinoma over an 11-year period revealed that 37.3% had pulmonary metastases. Review of the pathological evidence in questionable cases supported the validity of the diagnosis. This rather high figure is paralleled by the findings of others quoted in the literature. Dissemination in the lungs appears to take place early with respect to the time of diagnosis. Seventeen of 49 patients (34.7%) who died within 1 month of tissue diagnosis already had additional pulmonary foci. It was possible to identify intrapulmonary spread radiographically in over half of the cases despite the prevalence of concomitant pulmonary disease. Hence, x-ray examination is a useful means of establishing the existence of such metastases in pursuing clinical trials.", "contents": "Intrapulmonary metastases from bronchogenic carcinoma and their radiographic detection. Autopsies on 102 patients dying with bronchogenic carcinoma over an 11-year period revealed that 37.3% had pulmonary metastases. Review of the pathological evidence in questionable cases supported the validity of the diagnosis. This rather high figure is paralleled by the findings of others quoted in the literature. Dissemination in the lungs appears to take place early with respect to the time of diagnosis. Seventeen of 49 patients (34.7%) who died within 1 month of tissue diagnosis already had additional pulmonary foci. It was possible to identify intrapulmonary spread radiographically in over half of the cases despite the prevalence of concomitant pulmonary disease. Hence, x-ray examination is a useful means of establishing the existence of such metastases in pursuing clinical trials."}
{"id": "PMID:229981", "title": "Adjuvant systemic therapy of lung cancer.", "content": "Most patients with lung cancer subjected to surgical resection are likely to have residual tumor burdens which lead to clinical relapse and death. Unfortunately, none of the systemic therapies for squamous cell, large cell and adenocarcinoma of the lung have demonstrated curative potential either in the advanced disease or in the surgical adjuvant setting. Interest in clinical trials of adjuvant therapy in lung cancer have been rekindled by three factors: 1) reports indicating the value of immunotherapy, 2) preliminary encouraging experience with new chemotherapy programs, and 3) methodologies including stage- and cell type-specific clinical trials leading to better interpretation of results. These concepts have stimulated new treatment protocol studies within the NCI-sponsored Lung Cancer Study Group, and clinical cooperative groups.", "contents": "Adjuvant systemic therapy of lung cancer. Most patients with lung cancer subjected to surgical resection are likely to have residual tumor burdens which lead to clinical relapse and death. Unfortunately, none of the systemic therapies for squamous cell, large cell and adenocarcinoma of the lung have demonstrated curative potential either in the advanced disease or in the surgical adjuvant setting. Interest in clinical trials of adjuvant therapy in lung cancer have been rekindled by three factors: 1) reports indicating the value of immunotherapy, 2) preliminary encouraging experience with new chemotherapy programs, and 3) methodologies including stage- and cell type-specific clinical trials leading to better interpretation of results. These concepts have stimulated new treatment protocol studies within the NCI-sponsored Lung Cancer Study Group, and clinical cooperative groups."}
{"id": "PMID:229982", "title": "Adriamycin and cis-dichlorodiammineplatinum in nonresectable and metastatic carcinoma of the lung.", "content": "The combination of adriamycin and cis-dichlorodiammineplatinum (DDP) was evaluated in 20 patients with nonresectable and metastatic carcinoma of the lung. Both drugs were administered at a dosage of 60 mg/m2 intravenously every 3 weeks. The overall objective response rate was 40% (eight of 20 patients) with two complete responses (CR) and six partial responses (PR). Four of eight patients with small cell carcinoma responded (1 CR and 3 PR) and four of 12 patients with nonsmall cell carcinoma responded (1 CR and 3 PR). The median duration of response was greater than 36 weeks. The median survival of responders was 54 weeks. Nausea and vomiting were major side effects but rarely lasted longer than 2 days. Renal and bone marrow toxicities were generally minimal and controlled by dosage reduction. However, there was one death secondary to severe myelosuppression.", "contents": "Adriamycin and cis-dichlorodiammineplatinum in nonresectable and metastatic carcinoma of the lung. The combination of adriamycin and cis-dichlorodiammineplatinum (DDP) was evaluated in 20 patients with nonresectable and metastatic carcinoma of the lung. Both drugs were administered at a dosage of 60 mg/m2 intravenously every 3 weeks. The overall objective response rate was 40% (eight of 20 patients) with two complete responses (CR) and six partial responses (PR). Four of eight patients with small cell carcinoma responded (1 CR and 3 PR) and four of 12 patients with nonsmall cell carcinoma responded (1 CR and 3 PR). The median duration of response was greater than 36 weeks. The median survival of responders was 54 weeks. Nausea and vomiting were major side effects but rarely lasted longer than 2 days. Renal and bone marrow toxicities were generally minimal and controlled by dosage reduction. However, there was one death secondary to severe myelosuppression."}
{"id": "PMID:229983", "title": "Controlled study with BCNU vs. CCNU as adjuvant chemotherapy following surgery plus radiotherapy for glioblastoma multiforme.", "content": "From September, 1972 to December, 1976, 102 consecutive patients operated on for glioblastoma multiforme were randomized, after total or subtotal tumor resection, to receive irradiation alone, irradiation plus BCNU or irradiation plus CCNU. BCNU and CCNU adjuvant chemotherapy was repeated every 6--8 weeks as long as the patients remained in complete remission. Patients were comparable for median age, type of surgery, and histological grade III and IV. Radiotherapy was administered at the tumor dose of about 5000 rads in all three groups. The percent of optimal dose administered was 96% for BCNU and 93% for CCNU. In the group treated with radiotherapy alone (32 cases) the median survival was 10.5 months, while in the groups treated with BCNU (34 cases) and CCNU (36 cases) the median survival was 12 and 16 months, respectively. Both relapse-free (P = 0.05) and total survival (P = 0.03) were significantly improved only in patients who were treated with radiotherapy plus CCNU compared to patients receiving radiotherapy alone after surgery. Present results show that in resectable glioblastoma multiforme, a slightly improved survival rate can be achieved by the prolonged use of adjuvant CCNU following maximal surgical resection and radiotherapy. The cure rate was not improved.", "contents": "Controlled study with BCNU vs. CCNU as adjuvant chemotherapy following surgery plus radiotherapy for glioblastoma multiforme. From September, 1972 to December, 1976, 102 consecutive patients operated on for glioblastoma multiforme were randomized, after total or subtotal tumor resection, to receive irradiation alone, irradiation plus BCNU or irradiation plus CCNU. BCNU and CCNU adjuvant chemotherapy was repeated every 6--8 weeks as long as the patients remained in complete remission. Patients were comparable for median age, type of surgery, and histological grade III and IV. Radiotherapy was administered at the tumor dose of about 5000 rads in all three groups. The percent of optimal dose administered was 96% for BCNU and 93% for CCNU. In the group treated with radiotherapy alone (32 cases) the median survival was 10.5 months, while in the groups treated with BCNU (34 cases) and CCNU (36 cases) the median survival was 12 and 16 months, respectively. Both relapse-free (P = 0.05) and total survival (P = 0.03) were significantly improved only in patients who were treated with radiotherapy plus CCNU compared to patients receiving radiotherapy alone after surgery. Present results show that in resectable glioblastoma multiforme, a slightly improved survival rate can be achieved by the prolonged use of adjuvant CCNU following maximal surgical resection and radiotherapy. The cure rate was not improved."}
{"id": "PMID:229984", "title": "Streptozotocin: an inactive agent in small cell carcinoma.", "content": "Fifteen patients with advanced small cell carcinoma of the lung were treated with streptozotocin. No objective reponses were seen. A review of the literature reveals no objective response in a total of 56 patients, indicating that this agent is inactive as a single agent in small cell carcinoma.", "contents": "Streptozotocin: an inactive agent in small cell carcinoma. Fifteen patients with advanced small cell carcinoma of the lung were treated with streptozotocin. No objective reponses were seen. A review of the literature reveals no objective response in a total of 56 patients, indicating that this agent is inactive as a single agent in small cell carcinoma."}
{"id": "PMID:229985", "title": "Results of surgical therapy for lung carcinoma.", "content": "A series of 300 pulmonary resections in patients with lung carcinoma is presented. Total survival rate of the series since the operation, including surgical mortality, was 33% at 3 years and 24% at 5 years. The survival rate and surgical criteria were correlated, having better results when standard surgery was performed. The authors emphasize that the surgical figures of the series are of great value as the surgical indications were large and nonselective, with 85% of resectability in the thoracotomies.", "contents": "Results of surgical therapy for lung carcinoma. A series of 300 pulmonary resections in patients with lung carcinoma is presented. Total survival rate of the series since the operation, including surgical mortality, was 33% at 3 years and 24% at 5 years. The survival rate and surgical criteria were correlated, having better results when standard surgery was performed. The authors emphasize that the surgical figures of the series are of great value as the surgical indications were large and nonselective, with 85% of resectability in the thoracotomies."}
{"id": "PMID:229986", "title": "[Transfer of genetic information from T to B human lymphocytes during an immune response to herpes simplex virus].", "content": "Human blood lymphocytes carrying different allotypes were divided into B and T subpopulations and cultured in presence or in absence of ultraviolet inactivated Herpes Simplex Virus. Isolated B or T cells did not produce any antiherpetic activity. The B lymphocytes cultured in presence of 1 or 50% of the supernatant collected from virus exposed T cells synthesized on antiherpetic antibody with some allotypic markers of the T cell donor.", "contents": "[Transfer of genetic information from T to B human lymphocytes during an immune response to herpes simplex virus]. Human blood lymphocytes carrying different allotypes were divided into B and T subpopulations and cultured in presence or in absence of ultraviolet inactivated Herpes Simplex Virus. Isolated B or T cells did not produce any antiherpetic activity. The B lymphocytes cultured in presence of 1 or 50% of the supernatant collected from virus exposed T cells synthesized on antiherpetic antibody with some allotypic markers of the T cell donor."}
{"id": "PMID:229987", "title": "[Importance of protein-protein interactions for the structural integrity of membrane framents from Torpedo marmorata electric organ].", "content": "Electron spin resonance and electron microscopy were used to show that alkaline extraction of a 43,000 dalton protein from torpedo membrane induces structural destabilization of the membrane and rotational diffusion of the cholinergic receptor protein.", "contents": "[Importance of protein-protein interactions for the structural integrity of membrane framents from Torpedo marmorata electric organ]. Electron spin resonance and electron microscopy were used to show that alkaline extraction of a 43,000 dalton protein from torpedo membrane induces structural destabilization of the membrane and rotational diffusion of the cholinergic receptor protein."}
{"id": "PMID:229988", "title": "[Diptera of Calliphora genus, potential carriers and spreaders of swine vesicular disease virus].", "content": "Swine Vesicular Disease virus ingested by the adult fly Calliphora persists several days in the digestive tract of the insect and is eliminated in feces. The virus ingested by the insect at larval stage has been recovered from the digestive tract and feces of adult flies. Thus, the dissemination of the virus, even in a limited fashion, seems to be possible and attention is chiefly centered on the second process.", "contents": "[Diptera of Calliphora genus, potential carriers and spreaders of swine vesicular disease virus]. Swine Vesicular Disease virus ingested by the adult fly Calliphora persists several days in the digestive tract of the insect and is eliminated in feces. The virus ingested by the insect at larval stage has been recovered from the digestive tract and feces of adult flies. Thus, the dissemination of the virus, even in a limited fashion, seems to be possible and attention is chiefly centered on the second process."}
{"id": "PMID:229989", "title": "[New data on the intervention of cyclic monophosphate in the cardiac automatogenous process].", "content": "We present here some new holistic titrations related to the demonstration of the intervention of threshold endogenous values of cAMP as a trigger biochemical factor of heart automatogenic function.", "contents": "[New data on the intervention of cyclic monophosphate in the cardiac automatogenous process]. We present here some new holistic titrations related to the demonstration of the intervention of threshold endogenous values of cAMP as a trigger biochemical factor of heart automatogenic function."}
{"id": "PMID:229990", "title": "[Visualization of opiate receptors in the locus coeruleus of rats: high resolution radioautography after administration of a tritiated met-enkephalin analog].", "content": "Opiate receptor sites were visualized by high resolution radioautography in the locus coeruleus of the Rat following intraventricular injection of the met-enkephalin analogue FK 33-824 tritiated with a high specific activity (3H-FK). After administration of a tracer dose of 3H-FK, more than 75% of the radioactivity detected in the locus coeruleus is specifically bound to opiate receptor sites. These are distributed both between and inside neuronal perikarya. After administration of 3H-FK at high concentration, electron microscope radioautography shows the presence of specific opiate binding sites at the level of axo-somatic and axo-dendritic synaptic junctions. These synaptic binding sites could correspond to receptor sites for endogenous enkephalins.", "contents": "[Visualization of opiate receptors in the locus coeruleus of rats: high resolution radioautography after administration of a tritiated met-enkephalin analog]. Opiate receptor sites were visualized by high resolution radioautography in the locus coeruleus of the Rat following intraventricular injection of the met-enkephalin analogue FK 33-824 tritiated with a high specific activity (3H-FK). After administration of a tracer dose of 3H-FK, more than 75% of the radioactivity detected in the locus coeruleus is specifically bound to opiate receptor sites. These are distributed both between and inside neuronal perikarya. After administration of 3H-FK at high concentration, electron microscope radioautography shows the presence of specific opiate binding sites at the level of axo-somatic and axo-dendritic synaptic junctions. These synaptic binding sites could correspond to receptor sites for endogenous enkephalins."}
{"id": "PMID:229992", "title": "In vitro differences between the lymphocytes of normal subjects and atopics.", "content": "Recently evidence has accumulated that atopic disease is associated with a deficiency of thymus-derived (T) cells. This deficiency appears to be primary, rather than secondary to treatment or manifestations of the disease. Results of in vitro studies indicate that the deficiency is most pronounced in certain subpopulations of T cells, and therefore a disturbance of the balance between subsets of T cells, notably suppressor and helper T cells, may develop in vivo in atopics. Some results suggest that there is indeed a relative deficiency of suppressor T cells in atopic diseases, and thus the hyperproduction of IgE which is associated with these diseases may be explained. The cause of the T cell deficiency in atopy may be a basal cellular abnormality, manifested e.g. as increased sensitivity to inactivation by physiological substances, notably to agents which increase intracellular levels of cyclic AMP. It is equally possible that the T cell deficiency is a direct consequence of subnormal production of certain thymic hormones.", "contents": "In vitro differences between the lymphocytes of normal subjects and atopics. Recently evidence has accumulated that atopic disease is associated with a deficiency of thymus-derived (T) cells. This deficiency appears to be primary, rather than secondary to treatment or manifestations of the disease. Results of in vitro studies indicate that the deficiency is most pronounced in certain subpopulations of T cells, and therefore a disturbance of the balance between subsets of T cells, notably suppressor and helper T cells, may develop in vivo in atopics. Some results suggest that there is indeed a relative deficiency of suppressor T cells in atopic diseases, and thus the hyperproduction of IgE which is associated with these diseases may be explained. The cause of the T cell deficiency in atopy may be a basal cellular abnormality, manifested e.g. as increased sensitivity to inactivation by physiological substances, notably to agents which increase intracellular levels of cyclic AMP. It is equally possible that the T cell deficiency is a direct consequence of subnormal production of certain thymic hormones."}
{"id": "PMID:229994", "title": "Determination of cadmium in whole blood and urine by Zeeman atomic absorption spectroscopy.", "content": "Direct determination of cadmium in whole blood and urine can be achieved using Zeeman effect flameless atomic absorption spectroscopy. Within-run precision studies for whole blood cadmium determinations gave relative standard deviations of 11.3% and 6.3% for 0.53 micrograms/l and 3.16 micrograms/l, respectively. Within-run precision studies for the urine analyses yielded relative standard deviations of 11.3% and 5.2% for 0.62 micrograms/l and 2.48 micrograms/l, respectively. The detection limit is 0.12 micrograms/l in the diluted specimens. Thus, this methodology may be used to quantitate normal and toxic cadmium levels in whole blood and urine.", "contents": "Determination of cadmium in whole blood and urine by Zeeman atomic absorption spectroscopy. Direct determination of cadmium in whole blood and urine can be achieved using Zeeman effect flameless atomic absorption spectroscopy. Within-run precision studies for whole blood cadmium determinations gave relative standard deviations of 11.3% and 6.3% for 0.53 micrograms/l and 3.16 micrograms/l, respectively. Within-run precision studies for the urine analyses yielded relative standard deviations of 11.3% and 5.2% for 0.62 micrograms/l and 2.48 micrograms/l, respectively. The detection limit is 0.12 micrograms/l in the diluted specimens. Thus, this methodology may be used to quantitate normal and toxic cadmium levels in whole blood and urine."}
{"id": "PMID:229995", "title": "Experience with human growth hormone in Great Britain: the report of the MRC Working Party.", "content": "The Working Party on human growth hormone (hGH) has during the past decade developed a system for the evaluation and treatment of patients suffering from hGH lack. Today there are nineteen measurement centres in the United Kingdom at which patients are assessed and where the effects of therapy are monitored. The current supply of hGH, which is prepared from pituitary glands collected by pathologists in the National Health Service, is just enough to meet demand, but research conducted on behalf of the Working Party suggests that hGH deficiency is more common than has been thought and that the prevalence may be as high as one in 10 000. If, as is hoped, patients are diagnosed younger and more patients with partial deficiency are recognized, demand may soon outstrip supply. Work is in progress to define better methods of hGH production and optimal dose regimens, both of which will help to minimize the problem of supply and demand. A few children have anti-hGH antibodies, which block growth as a result of treatment. Improved hGH production techniques may result in a less antigenic product and the resolution of this problem. Many of the Working Party's activities began as research and have evolved into service. Because of this shift in emphasis, and although much research is still to be done, responsibility for provision of treatment with hGH transferred from the Medical Research Council to the Department of Health and Social Security in July 1977.", "contents": "Experience with human growth hormone in Great Britain: the report of the MRC Working Party. The Working Party on human growth hormone (hGH) has during the past decade developed a system for the evaluation and treatment of patients suffering from hGH lack. Today there are nineteen measurement centres in the United Kingdom at which patients are assessed and where the effects of therapy are monitored. The current supply of hGH, which is prepared from pituitary glands collected by pathologists in the National Health Service, is just enough to meet demand, but research conducted on behalf of the Working Party suggests that hGH deficiency is more common than has been thought and that the prevalence may be as high as one in 10 000. If, as is hoped, patients are diagnosed younger and more patients with partial deficiency are recognized, demand may soon outstrip supply. Work is in progress to define better methods of hGH production and optimal dose regimens, both of which will help to minimize the problem of supply and demand. A few children have anti-hGH antibodies, which block growth as a result of treatment. Improved hGH production techniques may result in a less antigenic product and the resolution of this problem. Many of the Working Party's activities began as research and have evolved into service. Because of this shift in emphasis, and although much research is still to be done, responsibility for provision of treatment with hGH transferred from the Medical Research Council to the Department of Health and Social Security in July 1977."}
{"id": "PMID:229996", "title": "Induction of puberty: long-term treatment with high-dose LHRH.", "content": "Gonadotropin releasing hormone 500 mcg was administered twice daily to four patients (two male, two female) with hypogonadotrophic hypogonadism due to LHRH deficiency, for a minimum of 1 year. Despite initially encouraging biochemical responses and physical changes in all four patients, gonadotrophin responsiveness waned, sex steroid levels were not maintained and pubertal development has not occurred. This diminishing responsiveness appears to be a severe limitation on the use of LHRH as a therapeutic agent.", "contents": "Induction of puberty: long-term treatment with high-dose LHRH. Gonadotropin releasing hormone 500 mcg was administered twice daily to four patients (two male, two female) with hypogonadotrophic hypogonadism due to LHRH deficiency, for a minimum of 1 year. Despite initially encouraging biochemical responses and physical changes in all four patients, gonadotrophin responsiveness waned, sex steroid levels were not maintained and pubertal development has not occurred. This diminishing responsiveness appears to be a severe limitation on the use of LHRH as a therapeutic agent."}
{"id": "PMID:229997", "title": "Radioimmunoassay of plasma 18-hydroxy-11-deoxycorticosterone and its response to ACTH.", "content": "A radioimmunoassay for the measurement of 18-OH-DOC in plasma was developed using an antiserum raised against the gamma-lactone derivative. The steroids with the greatest degree of cross reaction were 18-OH-corticosterone-gamma-lactone and aldosterone-gamma-lactone which showed cross-reactivities of 1.96% and 0.47% respectively. These and other interfering steroids were eliminated by chromatography of the extracts on columns of Sephadex LH-20. The lowest limit of detection of 18-OH-DOC in 1 ml of plasma corresponded to 33 pmol-1. The intra-assay precision was 9.7, 4.8 and 2.6% at 102.0, 316.1 and 1144.0 pmol 1(-1) respectively and the interassay precision was 15.3 and 5.4% at 71.3 and 404.7 pmol 1(-1) respectively. The amount of 18-OH-DOC measured (y) which showed a high degree of correlation (r = 0.999) with the amount added (x) to plasma in the range 240--1920 pmol 1(-1) could be predicted from the linear least squares equation y = 1.006x + 31.3. The concentration of 18-OH-DOC in ten normal subjects was 172.1 +/- 39.1 pmol 1(-1) at 09.00 h, 100.9 +/- 16.9 pmol 1(-1) at 12.00 h and 95.8 +/- 33.3 pmol 1(-1) at 16.30 h. Plasma 18-OH-DOC and cortisol levels were measured after various intravenous doses of ACTH in three patient with esential hypertension. Lower doses of ACTH caused similar percentage increases in both hormones but higher doses caused considerably greater increases in 18-OH-DOC. These results confirm the ACTH dependancy of 18-OH-DOC secretion.", "contents": "Radioimmunoassay of plasma 18-hydroxy-11-deoxycorticosterone and its response to ACTH. A radioimmunoassay for the measurement of 18-OH-DOC in plasma was developed using an antiserum raised against the gamma-lactone derivative. The steroids with the greatest degree of cross reaction were 18-OH-corticosterone-gamma-lactone and aldosterone-gamma-lactone which showed cross-reactivities of 1.96% and 0.47% respectively. These and other interfering steroids were eliminated by chromatography of the extracts on columns of Sephadex LH-20. The lowest limit of detection of 18-OH-DOC in 1 ml of plasma corresponded to 33 pmol-1. The intra-assay precision was 9.7, 4.8 and 2.6% at 102.0, 316.1 and 1144.0 pmol 1(-1) respectively and the interassay precision was 15.3 and 5.4% at 71.3 and 404.7 pmol 1(-1) respectively. The amount of 18-OH-DOC measured (y) which showed a high degree of correlation (r = 0.999) with the amount added (x) to plasma in the range 240--1920 pmol 1(-1) could be predicted from the linear least squares equation y = 1.006x + 31.3. The concentration of 18-OH-DOC in ten normal subjects was 172.1 +/- 39.1 pmol 1(-1) at 09.00 h, 100.9 +/- 16.9 pmol 1(-1) at 12.00 h and 95.8 +/- 33.3 pmol 1(-1) at 16.30 h. Plasma 18-OH-DOC and cortisol levels were measured after various intravenous doses of ACTH in three patient with esential hypertension. Lower doses of ACTH caused similar percentage increases in both hormones but higher doses caused considerably greater increases in 18-OH-DOC. These results confirm the ACTH dependancy of 18-OH-DOC secretion."}
{"id": "PMID:229998", "title": "The circadian variation of immunoreactive lipotrophin and its relationship to ACTH and growth hormone in man.", "content": "There is a clear circadian rhythm of plasma immunoreactive LPH in man with the trough occurring between 22.00 h and 03.00 h and the peak between 07.00 h and 08.00 h, immediately after waking. At all times circulating LPH and ACTH levels follow each other closely. However, no correlation was observed between LPH levels and either plasma GH or the stage of sleep.", "contents": "The circadian variation of immunoreactive lipotrophin and its relationship to ACTH and growth hormone in man. There is a clear circadian rhythm of plasma immunoreactive LPH in man with the trough occurring between 22.00 h and 03.00 h and the peak between 07.00 h and 08.00 h, immediately after waking. At all times circulating LPH and ACTH levels follow each other closely. However, no correlation was observed between LPH levels and either plasma GH or the stage of sleep."}
{"id": "PMID:229999", "title": "Intermittent Cushing's disease with spontaneous remission.", "content": "A patient with well documented Cushing's syndrome, associated with excessive secretion of ACTH, was studied over a 20 month period. During this time there were three episodes of spontaneous biochemical remission and except for a 7 day period of exacerbation the patient has had normal cortisol production for the last 15 months. During this recent prolonged remission period, repeat pituitary function testing demonstrated persistent abnormalities of the hypothalamic pituitary axis, in that ACTH failed to respond to a hypoglycaemic stimulus. However in all other respects adrenal function was normal with preservation of diurnal rhythmicity of cortisol and ACTH, and intact dexamethasone suppressability of cortisol. The additional unusual features of normal GH and TSH responses to stimulation, during either remission or exacerbation, suggest a subtle and localized hypothalamic defect in this case.", "contents": "Intermittent Cushing's disease with spontaneous remission. A patient with well documented Cushing's syndrome, associated with excessive secretion of ACTH, was studied over a 20 month period. During this time there were three episodes of spontaneous biochemical remission and except for a 7 day period of exacerbation the patient has had normal cortisol production for the last 15 months. During this recent prolonged remission period, repeat pituitary function testing demonstrated persistent abnormalities of the hypothalamic pituitary axis, in that ACTH failed to respond to a hypoglycaemic stimulus. However in all other respects adrenal function was normal with preservation of diurnal rhythmicity of cortisol and ACTH, and intact dexamethasone suppressability of cortisol. The additional unusual features of normal GH and TSH responses to stimulation, during either remission or exacerbation, suggest a subtle and localized hypothalamic defect in this case."}
{"id": "PMID:230000", "title": "Lp(a) phenotypes, other lipoprotein parameters, and a family history of coronary heart disease in middle-aged males.", "content": "In a study of 95 presumably healthy, 40-42-year old males from Northen Sweden, the Lp(a) phenotype distribution differed between those who had, and those who did not have one or more close relatives (parent or sib) with coronary heart disease. In the former group, 60% of the males were Lp(a+), as opposed to 28% in the latter group. Thus, in the homogeneous population sample studied, analysis of the normal inherited Lp(a) variation permitted the identification of distinct subpopulations, with respect to familial occurrence of coronary heart disease. None of a series of other parameters distinguished such sub-populations. The results reported are in agreement with our previous finding of a close association between phenotype Lp(a+) and risk of contracting coronary heart disease.", "contents": "Lp(a) phenotypes, other lipoprotein parameters, and a family history of coronary heart disease in middle-aged males. In a study of 95 presumably healthy, 40-42-year old males from Northen Sweden, the Lp(a) phenotype distribution differed between those who had, and those who did not have one or more close relatives (parent or sib) with coronary heart disease. In the former group, 60% of the males were Lp(a+), as opposed to 28% in the latter group. Thus, in the homogeneous population sample studied, analysis of the normal inherited Lp(a) variation permitted the identification of distinct subpopulations, with respect to familial occurrence of coronary heart disease. None of a series of other parameters distinguished such sub-populations. The results reported are in agreement with our previous finding of a close association between phenotype Lp(a+) and risk of contracting coronary heart disease."}
{"id": "PMID:230011", "title": "Preliminary experience with parenteral mecillinam.", "content": "Case reports are reviewed of 26 patients, mainly with severe Gram-negative infections, treatment with parenteral mecillinam. Twenty-three patients received other antibiotics in addition to mecillinam. In 19 patients, potentially synergistic antimicrobial therapy was given. Overall, a beneficial clinical effect was recorded in 17 (68%) of the 25 patients assessed. A better response was observed in those patients who had not received other antibiotics before treatment with mecillinam was instituted. It is concluded that parenteral mecillinam may have an important role in the treatment of severe Gram-negative infections.", "contents": "Preliminary experience with parenteral mecillinam. Case reports are reviewed of 26 patients, mainly with severe Gram-negative infections, treatment with parenteral mecillinam. Twenty-three patients received other antibiotics in addition to mecillinam. In 19 patients, potentially synergistic antimicrobial therapy was given. Overall, a beneficial clinical effect was recorded in 17 (68%) of the 25 patients assessed. A better response was observed in those patients who had not received other antibiotics before treatment with mecillinam was instituted. It is concluded that parenteral mecillinam may have an important role in the treatment of severe Gram-negative infections."}
{"id": "PMID:230013", "title": "Exogenous DNA transcription in cells with their native DNA inhibited. 1. DNA incorporation into homologous and heterologous cells.", "content": "The incorporation of mouse S-EAC DNA into homologous normal cells (mouse embryo secondary cultures), and into heterologous cancer cells (TC-SV40 line), with both systems having their native DNA blocked by BrUdR incorporation, was studied. 3H-TdR-DNA was inoculated with DEAE-D to protect it and to potentiate its incorporation, the process being autoradiograohically controlled. The amount of incorporated DNA was radioisotopically determined, and the incorporation process was studied by analysing the fractions obtained after density gradient centrifugation separation of the inoculated cells DNA. Receptivity was greater in those cells inoculated with DEAE-D-protected DNA. The incorporation was slightly greater for cells whose DNA had been blocked by BrUdR incorporation, and for homologous with respect to heterologous cells. In those cells inoculated while the DNA blockade was incomplete, part of the inoculated DNA became incorporated into the cell genome (L-H chains). However, in the completely blocked cells it could not be determined if the incorporation occurred in a lysogenic-like or in an episomic-like form.", "contents": "Exogenous DNA transcription in cells with their native DNA inhibited. 1. DNA incorporation into homologous and heterologous cells. The incorporation of mouse S-EAC DNA into homologous normal cells (mouse embryo secondary cultures), and into heterologous cancer cells (TC-SV40 line), with both systems having their native DNA blocked by BrUdR incorporation, was studied. 3H-TdR-DNA was inoculated with DEAE-D to protect it and to potentiate its incorporation, the process being autoradiograohically controlled. The amount of incorporated DNA was radioisotopically determined, and the incorporation process was studied by analysing the fractions obtained after density gradient centrifugation separation of the inoculated cells DNA. Receptivity was greater in those cells inoculated with DEAE-D-protected DNA. The incorporation was slightly greater for cells whose DNA had been blocked by BrUdR incorporation, and for homologous with respect to heterologous cells. In those cells inoculated while the DNA blockade was incomplete, part of the inoculated DNA became incorporated into the cell genome (L-H chains). However, in the completely blocked cells it could not be determined if the incorporation occurred in a lysogenic-like or in an episomic-like form."}
{"id": "PMID:230014", "title": "On the pathogenicity of Entamoeba histolytica. Part I: The role of bacterial associate on the modification of virulence of E. histolytica.", "content": "Of the 3 strains of Escherichia coli used, only Milner A strain was found capable of modifying the virulence of Entamoeba histolytica. None out of twenty-four hamsters inoculated with either 5 X 10(5) of axenically-cultured E. histolytica of NIH: 200 strain, or 1 X 10(7) of Esch. coli (A, B or C strains), was found to have amebic liver abscess. Whereas one out of six hamsters inoculated with the same number of amebae preincubated for 12 hrs with Esch. coli of Milner A strain was found to have abscess. The role of bacterial associate seems to be nothing but provides a more suitable environment for amebae, thus enable them to survive longer and endow them more time to adapt themselves to the given new environment. From liver abscess E. histolytica was recovered and successfully reaxenized. These amebae were capable of producing liver abscess, therefore the virulence seemed to be inheritable.", "contents": "On the pathogenicity of Entamoeba histolytica. Part I: The role of bacterial associate on the modification of virulence of E. histolytica. Of the 3 strains of Escherichia coli used, only Milner A strain was found capable of modifying the virulence of Entamoeba histolytica. None out of twenty-four hamsters inoculated with either 5 X 10(5) of axenically-cultured E. histolytica of NIH: 200 strain, or 1 X 10(7) of Esch. coli (A, B or C strains), was found to have amebic liver abscess. Whereas one out of six hamsters inoculated with the same number of amebae preincubated for 12 hrs with Esch. coli of Milner A strain was found to have abscess. The role of bacterial associate seems to be nothing but provides a more suitable environment for amebae, thus enable them to survive longer and endow them more time to adapt themselves to the given new environment. From liver abscess E. histolytica was recovered and successfully reaxenized. These amebae were capable of producing liver abscess, therefore the virulence seemed to be inheritable."}
{"id": "PMID:230016", "title": "Adrenergic receptor function is different in male and female patients with essential hypertension.", "content": "As plasma norepinephrine (NE) levels may be similar in hypertensive and normotensive subjects, the sensitivity of adrenergic receptors was investigated in patients with essential hypertension and normotensive subjects of similar age and sex. Alpha-adrenergic receptor sensitivity was measured in platelets by the specific binding of [3H]dihydroergocryptine and the NE inhibition of prostaglandin E1 (PGE1)-stimulated cyclic AMP (cAMP) production. The number of alpha-adrenergic receptors in platelets from hypertensive women was 1.5 times that in the platelets from normotensive ones, with no differences between hypertensive and normotensive women or between men and women in the affinity of the alpha-adrenergic receptor for [3H]dihydroergocryptine. PGE1-stimulated cAMP production was half as great in hypertensive as in normotensive men, while NE inhibition of PGE1-stimulated cAMP production was similar in hypertensive and normotensive men and women. [3H]Dihydroergoeryptine binding in female hypertensives, and PGE1-stimulated cAMP in male hypertensives did not differ from that in sex-matched controls. The sensitivity of the beta-adrenergic receptor, measured by [3H]dihydroalprenolol binding and cAMP production was similar in hypertensive and normotensive subjects.", "contents": "Adrenergic receptor function is different in male and female patients with essential hypertension. As plasma norepinephrine (NE) levels may be similar in hypertensive and normotensive subjects, the sensitivity of adrenergic receptors was investigated in patients with essential hypertension and normotensive subjects of similar age and sex. Alpha-adrenergic receptor sensitivity was measured in platelets by the specific binding of [3H]dihydroergocryptine and the NE inhibition of prostaglandin E1 (PGE1)-stimulated cyclic AMP (cAMP) production. The number of alpha-adrenergic receptors in platelets from hypertensive women was 1.5 times that in the platelets from normotensive ones, with no differences between hypertensive and normotensive women or between men and women in the affinity of the alpha-adrenergic receptor for [3H]dihydroergocryptine. PGE1-stimulated cAMP production was half as great in hypertensive as in normotensive men, while NE inhibition of PGE1-stimulated cAMP production was similar in hypertensive and normotensive men and women. [3H]Dihydroergoeryptine binding in female hypertensives, and PGE1-stimulated cAMP in male hypertensives did not differ from that in sex-matched controls. The sensitivity of the beta-adrenergic receptor, measured by [3H]dihydroalprenolol binding and cAMP production was similar in hypertensive and normotensive subjects."}
{"id": "PMID:230023", "title": "[Interactions of low density lipoproteins with glycosaminoglycans and foam cells within the atherosclerotic aorta (author's transl)].", "content": "Very low and low density lipoproteins (VLDL and LDL) isolated from aorta's intima in salt solution were predominantly, associated in complex with glycosaminoglycans (GAG): hyaluronic acid, chondroitinsulfate A(C), heparin. Heparin was detected mainly in complex, isolated from fibrosis plaque. Studying of interaction between LDL and foam cells showed that cells in situ as far as under their incubation in medium with llow LDL concentration primarily accumulated lipid of lipoprotein particles. Incubation foam cells under increased concentration of lipoprotein in medium led to greater entry of radioactivity into the cells. However, there was less tendency for primarily lipid accumulation. Increase of LDL concentration correlated with larger cell's CO2 production. GAG prevented this effect of LDL. Besides LDL uptake was decreased in this condition too. It is possible that GAG effect lipoprotein properties and in such a way the character of their interaction with cells.", "contents": "[Interactions of low density lipoproteins with glycosaminoglycans and foam cells within the atherosclerotic aorta (author's transl)]. Very low and low density lipoproteins (VLDL and LDL) isolated from aorta's intima in salt solution were predominantly, associated in complex with glycosaminoglycans (GAG): hyaluronic acid, chondroitinsulfate A(C), heparin. Heparin was detected mainly in complex, isolated from fibrosis plaque. Studying of interaction between LDL and foam cells showed that cells in situ as far as under their incubation in medium with llow LDL concentration primarily accumulated lipid of lipoprotein particles. Incubation foam cells under increased concentration of lipoprotein in medium led to greater entry of radioactivity into the cells. However, there was less tendency for primarily lipid accumulation. Increase of LDL concentration correlated with larger cell's CO2 production. GAG prevented this effect of LDL. Besides LDL uptake was decreased in this condition too. It is possible that GAG effect lipoprotein properties and in such a way the character of their interaction with cells."}
{"id": "PMID:230024", "title": "[Population studies of adenylate kinase (AK) in Bulgaria].", "content": "The author carried out studies on 600 Bulgarians from the south Bulgaria (the town of Plovdiv) and 232 gypsies. There was gene frequency of AK1=0.9633 and AK2=0.0367 in the Bulgariana and respectively AK1=0.9784 and AK2=0.0216 in the gypsies as the differences between both populations were insignificant. All data, published up to now, were summarised connected with the examination of the Bulgarians for AK (1278) and the estimated mean values for gene frequencies were: AK1=0.9648 and =K2=0.0352). Gene frequencies of the Bulgarians, compared with other populations, revealed that they were in the ranges of the mean European values for gene frequencies and differed substantially from those of the nergos and some Asian nations (Japanese, Chinese). The theoretical probability for excluding fatherhood by means of the system of Ak for the Bulgarian was 3.28%.", "contents": "[Population studies of adenylate kinase (AK) in Bulgaria]. The author carried out studies on 600 Bulgarians from the south Bulgaria (the town of Plovdiv) and 232 gypsies. There was gene frequency of AK1=0.9633 and AK2=0.0367 in the Bulgariana and respectively AK1=0.9784 and AK2=0.0216 in the gypsies as the differences between both populations were insignificant. All data, published up to now, were summarised connected with the examination of the Bulgarians for AK (1278) and the estimated mean values for gene frequencies were: AK1=0.9648 and =K2=0.0352). Gene frequencies of the Bulgarians, compared with other populations, revealed that they were in the ranges of the mean European values for gene frequencies and differed substantially from those of the nergos and some Asian nations (Japanese, Chinese). The theoretical probability for excluding fatherhood by means of the system of Ak for the Bulgarian was 3.28%."}
{"id": "PMID:230025", "title": "[Effect of biological agents on glucose-14C utilization by erythrocytes varying in age].", "content": "The authors examined young, adult and old erythrocytes from rabbits, aged 15,35 days and 3--4 years. They measured the amount of glucose 14C transfere and metabolized by the erythrocytes during 2-hour incubation at 37 degrees C in a suitable medium. A series of erythrocytes from the three age groups were examined without treatment with chemical agents. Other series of erythrocytes were treated 1 degree minutes before incubation and during its performance with various biological active substances insulin, ACTH, adrenaline, STH, 3AMP, ClCl2. There were differences due to the age in the nontreated erythrocytes. Erythrocytes increased their permeability for grucose and thus its amount was raised in the cells after treatment with insulin. ACTH inhibited this process. Adrenaline, STH, 3AMP and CaCl increased the amount of glucose in the young erythrocytes, obtained from the young animals. The data showed differences in the transfer of glucose 14C and its metabolism in accordance with the chemical and biological properties of the biological agents as well as in accordance with the age of erythrocytes and the animals.", "contents": "[Effect of biological agents on glucose-14C utilization by erythrocytes varying in age]. The authors examined young, adult and old erythrocytes from rabbits, aged 15,35 days and 3--4 years. They measured the amount of glucose 14C transfere and metabolized by the erythrocytes during 2-hour incubation at 37 degrees C in a suitable medium. A series of erythrocytes from the three age groups were examined without treatment with chemical agents. Other series of erythrocytes were treated 1 degree minutes before incubation and during its performance with various biological active substances insulin, ACTH, adrenaline, STH, 3AMP, ClCl2. There were differences due to the age in the nontreated erythrocytes. Erythrocytes increased their permeability for grucose and thus its amount was raised in the cells after treatment with insulin. ACTH inhibited this process. Adrenaline, STH, 3AMP and CaCl increased the amount of glucose in the young erythrocytes, obtained from the young animals. The data showed differences in the transfer of glucose 14C and its metabolism in accordance with the chemical and biological properties of the biological agents as well as in accordance with the age of erythrocytes and the animals."}
{"id": "PMID:230026", "title": "[Cesium].", "content": "Cesium is an alkaline metal close to Rubidium, which is studied in psychopharmacology in the prospect of a possible antidepressive effect. It has stimulating properties of the motor activity on the animal, antagonizes some sedative substances but does not modify either self-stimulation behaviour or induced agressivity. Given in large doses, Cesium presents hypertensive effects bound with a stimulation of the adrenal Epinephrine secretion. As for the synapses Cesium increases the neuro-transmitter release. However the Norepinephrine turn-over is not modified in the central nervous system while that of Serotonin is increased as well as the cerebral concentrations of Tryptophan, Serotonin and 5.HIAA. These very fragmentary data about the toxico-pharmacological properties of Cesium, as well as the very prolonged half-life of this ion (from 50 to 100 days), explain that contrary to Rubidium it has not still been used in man.", "contents": "[Cesium]. Cesium is an alkaline metal close to Rubidium, which is studied in psychopharmacology in the prospect of a possible antidepressive effect. It has stimulating properties of the motor activity on the animal, antagonizes some sedative substances but does not modify either self-stimulation behaviour or induced agressivity. Given in large doses, Cesium presents hypertensive effects bound with a stimulation of the adrenal Epinephrine secretion. As for the synapses Cesium increases the neuro-transmitter release. However the Norepinephrine turn-over is not modified in the central nervous system while that of Serotonin is increased as well as the cerebral concentrations of Tryptophan, Serotonin and 5.HIAA. These very fragmentary data about the toxico-pharmacological properties of Cesium, as well as the very prolonged half-life of this ion (from 50 to 100 days), explain that contrary to Rubidium it has not still been used in man."}
{"id": "PMID:230027", "title": "Effects of (Bu2)-cAMP and clomiphene on serum concentrations of several proteins and hormones in gonadectomized monkeys.", "content": "Sixteen mumol kg-1 of dibutyryl cyclic adenosine 3',5'-monophosphate [(Bu)2cAMP] given intramuscularly to gonadectomized green monkeys (Cercopithecus aetheops sabeus) for two-week periods, produced a significant elevation in the serum concentrations of thyroxine-binding globulin (TBG), fibrinogen, and haptoglobin. No changes were noted in cortisol-binding golbulin (CBG), cortisol, thyroxine, transferrin, total proteins, and albumin. Clomiphene citrate (12.5 mg orally) given concomitantly with (Bu)2cAMP blocked partially the (Bu)2cAMP-induced fibrinogen increment, but not the change in TBG concentration.", "contents": "Effects of (Bu2)-cAMP and clomiphene on serum concentrations of several proteins and hormones in gonadectomized monkeys. Sixteen mumol kg-1 of dibutyryl cyclic adenosine 3',5'-monophosphate [(Bu)2cAMP] given intramuscularly to gonadectomized green monkeys (Cercopithecus aetheops sabeus) for two-week periods, produced a significant elevation in the serum concentrations of thyroxine-binding globulin (TBG), fibrinogen, and haptoglobin. No changes were noted in cortisol-binding golbulin (CBG), cortisol, thyroxine, transferrin, total proteins, and albumin. Clomiphene citrate (12.5 mg orally) given concomitantly with (Bu)2cAMP blocked partially the (Bu)2cAMP-induced fibrinogen increment, but not the change in TBG concentration."}
{"id": "PMID:230028", "title": "Preventive effect of diethyldithiocarbamate on experimental diabetes produced by dithisone and 8-oxychinoline.", "content": "Diethyldithiocarbamate sodium (DDC)--a compound forming complexes with metal ions-did not change the structure of endocrine pancreas and did not affect the glycemia after the repeated administration of a dose of 250 mg kg-1 while a single dose of 500 or 1000 mg kg-1 increased the glycemia for 2 to 4 h in most of rabbits tested. DDC injected in similar doses prevented a diabetogenic action of dithisone and of a number of 8-oxichinoline derivatives. This effect appeared very rapidly and persisted for several hours being dependent on a dose of DDC and on the interval between its administration and the injection of diabetogenic compounds. It was concluded that DDC forms stable complexes with zinc ions in pancreatic beta-cells which appear to be resistant towards the action of diabetogenic compounds directed selectively to the blocking of zinc ions too and thus to the development of experimental diabetes.", "contents": "Preventive effect of diethyldithiocarbamate on experimental diabetes produced by dithisone and 8-oxychinoline. Diethyldithiocarbamate sodium (DDC)--a compound forming complexes with metal ions-did not change the structure of endocrine pancreas and did not affect the glycemia after the repeated administration of a dose of 250 mg kg-1 while a single dose of 500 or 1000 mg kg-1 increased the glycemia for 2 to 4 h in most of rabbits tested. DDC injected in similar doses prevented a diabetogenic action of dithisone and of a number of 8-oxichinoline derivatives. This effect appeared very rapidly and persisted for several hours being dependent on a dose of DDC and on the interval between its administration and the injection of diabetogenic compounds. It was concluded that DDC forms stable complexes with zinc ions in pancreatic beta-cells which appear to be resistant towards the action of diabetogenic compounds directed selectively to the blocking of zinc ions too and thus to the development of experimental diabetes."}
{"id": "PMID:230029", "title": "Study of peptides inhibiting the angiotensin-converting enzyme of human seminal plasma.", "content": "Several peptides were investigated for their inhibitory capacity against dipeptidyl carboxypeptidase (angiotensin-converting enzyme) from human seminal fluid. The strongest inhibitor was the nonapeptide SQ 20881. A marked inhibition was also shown by the compounds Phe-Ala-Pro and Boc-Phe-Ala-Pro, which behaved as competitive inhibitors. Among the peptides related to angiotensin, angiotensin III was the strongest inhibitor, followed by angiotensin II and the C-terminal hexapeptide of angiotensin II. The results indicate the dipeptidyl carboxypeptidase of human semen is very similar to pulmonary dipeptidyl carboxypeptidase in its susceptibility to peptide inhibitors. In view of these and other previously reported similarities, it is possible that both enzymes are identical.", "contents": "Study of peptides inhibiting the angiotensin-converting enzyme of human seminal plasma. Several peptides were investigated for their inhibitory capacity against dipeptidyl carboxypeptidase (angiotensin-converting enzyme) from human seminal fluid. The strongest inhibitor was the nonapeptide SQ 20881. A marked inhibition was also shown by the compounds Phe-Ala-Pro and Boc-Phe-Ala-Pro, which behaved as competitive inhibitors. Among the peptides related to angiotensin, angiotensin III was the strongest inhibitor, followed by angiotensin II and the C-terminal hexapeptide of angiotensin II. The results indicate the dipeptidyl carboxypeptidase of human semen is very similar to pulmonary dipeptidyl carboxypeptidase in its susceptibility to peptide inhibitors. In view of these and other previously reported similarities, it is possible that both enzymes are identical."}
{"id": "PMID:230030", "title": "Chemical and enzymatic characterization of the collagenase from the insect Hypoderma lineatum.", "content": "The collagenase from the larvae Hypoderma lineatum, with a molecular weight of 24 000 and isoelectric point of 4.1, was obtained in homogeneous form by ion-exchange chromatography. It is stoichiometrically inhibited by diisopropylfluorophosphate. On the other hand it is unaffected by ethylenediaminetetraacetate, p-chloromercuribenzoate, dithiothreitol, N-tosyllysine chloromethyl ketone, N-tosylphenylalanine chloromethyl ketone and ovomucoid trypsin inhibitor. The enzyme which degrades native collagen in its helical parts, has a specific activity on thermally reconstituted collagen fibrils of 150 micrograms collagen degraded x min-1 x (mg enzyme)-1 at 37 degrees C. It hydrolyses casein but has no esterolytic activity characteristic of trypsin, chymotrypsin nor elastase. It has no action on the synthetic peptide 4-phenylazobenzyloxycarbonyl-L-prolyl-L-leucyl-L-glycyl-L-prolyl-D-arginine. The amino acid composition of Hypoderma collagenase indicates a distinct similarity with the serine proteinases of the trypsin family and with another athropode serine collagenase, that of the fiddler crab Uca pugilator. This suggests that eucaryotic collagenases with digestive rather than morphogenic function represent a new category of members of the trypsin family.", "contents": "Chemical and enzymatic characterization of the collagenase from the insect Hypoderma lineatum. The collagenase from the larvae Hypoderma lineatum, with a molecular weight of 24 000 and isoelectric point of 4.1, was obtained in homogeneous form by ion-exchange chromatography. It is stoichiometrically inhibited by diisopropylfluorophosphate. On the other hand it is unaffected by ethylenediaminetetraacetate, p-chloromercuribenzoate, dithiothreitol, N-tosyllysine chloromethyl ketone, N-tosylphenylalanine chloromethyl ketone and ovomucoid trypsin inhibitor. The enzyme which degrades native collagen in its helical parts, has a specific activity on thermally reconstituted collagen fibrils of 150 micrograms collagen degraded x min-1 x (mg enzyme)-1 at 37 degrees C. It hydrolyses casein but has no esterolytic activity characteristic of trypsin, chymotrypsin nor elastase. It has no action on the synthetic peptide 4-phenylazobenzyloxycarbonyl-L-prolyl-L-leucyl-L-glycyl-L-prolyl-D-arginine. The amino acid composition of Hypoderma collagenase indicates a distinct similarity with the serine proteinases of the trypsin family and with another athropode serine collagenase, that of the fiddler crab Uca pugilator. This suggests that eucaryotic collagenases with digestive rather than morphogenic function represent a new category of members of the trypsin family."}
{"id": "PMID:230031", "title": "Microbial production of methyl ketones. Purification and properties of a secondary alcohol dehydrogenase from yeast.", "content": "Cell-free extracts derived from yeasts Candida utilis ATCC 26387, Hansenula polymorpha ATCC 26012, Pichia sp. NRRL-Y-11328 Torulopsis sp. strain A1 and Kloeckera sp. strain A2 catalyzed an NAD+-dependent oxidation of secondary alcohols (2-propanol, 2-butanol, 2-pentanol, 2-hexanol) to the corresponding methyl ketones (acetone, 2-butanone, 2-pentanone, 2-hexanone). We have purified a NAD+-specific secondary alcohol dehydrogenase from methanol-grown yeast, Pichia sp. The purified enzyme is homogenous as judged by polyacrylamide gel electrophoresis. The purified enzyme catalyzed the oxidation of secondary alcohols to the corresponding methyl ketones in the presence of NAD+ as an electron acceptor. Primary alcohols were not oxidized by the purified enzyme. The optimum pH for oxidation of secondary alcohols by the purified enzyme is 8.0. The molecular weight of the purified enzyme as determined by gel filtration is 98 000 and subunit size as determined by sodium dodecyl sulfate gel electrophoresis is 48 000. The activity of the purified secondary alcohol dehydrogenase was inhibited by sulfhydryl inhibitors and metal-binding agents.", "contents": "Microbial production of methyl ketones. Purification and properties of a secondary alcohol dehydrogenase from yeast. Cell-free extracts derived from yeasts Candida utilis ATCC 26387, Hansenula polymorpha ATCC 26012, Pichia sp. NRRL-Y-11328 Torulopsis sp. strain A1 and Kloeckera sp. strain A2 catalyzed an NAD+-dependent oxidation of secondary alcohols (2-propanol, 2-butanol, 2-pentanol, 2-hexanol) to the corresponding methyl ketones (acetone, 2-butanone, 2-pentanone, 2-hexanone). We have purified a NAD+-specific secondary alcohol dehydrogenase from methanol-grown yeast, Pichia sp. The purified enzyme is homogenous as judged by polyacrylamide gel electrophoresis. The purified enzyme catalyzed the oxidation of secondary alcohols to the corresponding methyl ketones in the presence of NAD+ as an electron acceptor. Primary alcohols were not oxidized by the purified enzyme. The optimum pH for oxidation of secondary alcohols by the purified enzyme is 8.0. The molecular weight of the purified enzyme as determined by gel filtration is 98 000 and subunit size as determined by sodium dodecyl sulfate gel electrophoresis is 48 000. The activity of the purified secondary alcohol dehydrogenase was inhibited by sulfhydryl inhibitors and metal-binding agents."}
{"id": "PMID:230032", "title": "Inactivation of gluconeogenic enzymes in glycolytic mutants of Saccharomyces cerevisiae.", "content": "Yeast mutants blocked at different steps of the glycolytic pathways have been used to study the inactivation of several gluconeogenic enzymes upon addition of sugars. While phosphorylation of the sugars appears a requisite for the inactivation of fructose 1,6-bisphosphatase and phosphoenol-pyruvate carboxykinase, malate dehydrogenase is inactivated by fructose in mutants lacking hexokinase. The normal inactivation elicited by glucose in a mutant lacking phosphofructokinase indicates that the process does not require metabolism of the sugar beyond hexose monophosphates. A possible role for ATP in the inactivation process is suggested.", "contents": "Inactivation of gluconeogenic enzymes in glycolytic mutants of Saccharomyces cerevisiae. Yeast mutants blocked at different steps of the glycolytic pathways have been used to study the inactivation of several gluconeogenic enzymes upon addition of sugars. While phosphorylation of the sugars appears a requisite for the inactivation of fructose 1,6-bisphosphatase and phosphoenol-pyruvate carboxykinase, malate dehydrogenase is inactivated by fructose in mutants lacking hexokinase. The normal inactivation elicited by glucose in a mutant lacking phosphofructokinase indicates that the process does not require metabolism of the sugar beyond hexose monophosphates. A possible role for ATP in the inactivation process is suggested."}
{"id": "PMID:230033", "title": "Studies on a mutant form of Escherichia coli citrate synthase desensitised to allosteric effectors.", "content": "Naturally occurring citrate synthases fall into distinct molecular and catalytic types. Gram-negative bacteria produce a 'large' enzyme, allosterically inhibited by NADH and, in the facultative anaerobes such as Escherichia coli, also by 2-oxoglutarate. On the other hand, Gram-positive bacteria and all eukaryotes produce a 'small' citrate synthase which is insensitive to these metabolites. As a complement to structure-function studies we have explored the possibility of genetically altering one type of citrate synthase to the other. By mutagenesis and suitable selection we have succeeded in isolating a mutant of E. coli whose citrate synthase is both 'small' and insensitive to NADH and 2-oxoglutarate. Some characteristics of the enzyme are described. Such mutant enzymes offer a novel approach to the study of citrate synthase, its regulation and its natural diversity.", "contents": "Studies on a mutant form of Escherichia coli citrate synthase desensitised to allosteric effectors. Naturally occurring citrate synthases fall into distinct molecular and catalytic types. Gram-negative bacteria produce a 'large' enzyme, allosterically inhibited by NADH and, in the facultative anaerobes such as Escherichia coli, also by 2-oxoglutarate. On the other hand, Gram-positive bacteria and all eukaryotes produce a 'small' citrate synthase which is insensitive to these metabolites. As a complement to structure-function studies we have explored the possibility of genetically altering one type of citrate synthase to the other. By mutagenesis and suitable selection we have succeeded in isolating a mutant of E. coli whose citrate synthase is both 'small' and insensitive to NADH and 2-oxoglutarate. Some characteristics of the enzyme are described. Such mutant enzymes offer a novel approach to the study of citrate synthase, its regulation and its natural diversity."}
{"id": "PMID:230034", "title": "A model for the chemical interactions of adenosine 3':5'-monophosphate with the R subunit of protein kinase type I. Refinement of the cyclic phosphate binding moiety of protein kinase type I.", "content": "The cAMP receptor site in the regulatory subunit of adenosine 3':5'-monophosphate (cAMP)-dependent protein kinase type I was mapped using analogues of cAMP in which the ribose phosphate moiety was systematically modified. Electronical alteration of the cyclophosphate ring at the 3' and 5' positions by sulfur and nitrogen decreased the affinity of these analogues towards the kinase. Substituents at these positions are not tolerated. Testing the separated diastereomers of derivatives in which one of the exocyclic oxygens at the phosphorus has been substituted by sulfur, it was found that one diastereoisomer is preferentially recognized. Based on these results it is proposed that the hydrophylic cyclic phosphate-ribose moiety of cAMP is bound to the kinase via its 3' and 5'-oxygens, the 2'-hydroxy group and the negative charge in a fixed position. Based on our and other published results it is further proposed, that the adenine moiety is bound in a hydrophobic cleft without any hydrogen bond interactions. The chemical interactions between cAMP and the R subunit of protein kinase type I differ from those found for the binding of cAMP to the chemoreceptor of Dictyostelium discoideum [18].", "contents": "A model for the chemical interactions of adenosine 3':5'-monophosphate with the R subunit of protein kinase type I. Refinement of the cyclic phosphate binding moiety of protein kinase type I. The cAMP receptor site in the regulatory subunit of adenosine 3':5'-monophosphate (cAMP)-dependent protein kinase type I was mapped using analogues of cAMP in which the ribose phosphate moiety was systematically modified. Electronical alteration of the cyclophosphate ring at the 3' and 5' positions by sulfur and nitrogen decreased the affinity of these analogues towards the kinase. Substituents at these positions are not tolerated. Testing the separated diastereomers of derivatives in which one of the exocyclic oxygens at the phosphorus has been substituted by sulfur, it was found that one diastereoisomer is preferentially recognized. Based on these results it is proposed that the hydrophylic cyclic phosphate-ribose moiety of cAMP is bound to the kinase via its 3' and 5'-oxygens, the 2'-hydroxy group and the negative charge in a fixed position. Based on our and other published results it is further proposed, that the adenine moiety is bound in a hydrophobic cleft without any hydrogen bond interactions. The chemical interactions between cAMP and the R subunit of protein kinase type I differ from those found for the binding of cAMP to the chemoreceptor of Dictyostelium discoideum [18]."}
{"id": "PMID:230035", "title": "Bile salt binding to serum components. Taurocholate incorporation into high-density lipoprotein revealed by photoaffinity labelling.", "content": "1. Photoaffinity labelling of human serum albumin with the sodium salts of (3 beta-azido-7 alpha,12 alpha-dihydroxy-5 beta-cholan-24-oyl)-2-amino[2(-3)H (N)]ethanesulfonic acid, (7,7-azo-3 alpha,12 alpha-dihydroxy-5 beta-cholan-24-oyl)-2-amino[2(-3)H (N)]ethanesulfonic acid and (11 zeta-azido-12-oxo-3 alpha,7 alpha-dihydroxy-5 beta-cholan-24-oyl)-2-amino[2(-3)H (N)]ethanesulfonic acid resulted, in each case, in a considerable covalent incorporation of radioactivity into the protein. 2. Photoaffinity labelling of whole serum, obtained from fasting test persons, revealed with all three photolabile derivatives of taurocholate at the physiological concentration of 2.1 microM the incorporation of radioactivity not only into albumin but also into high-density lipoprotein, as demonstrated by density gradient centrifugation and by immunological characterization. 3. The bulk of radioactivity incorporated into high-density lipoprotein by photoaffinity labelling of whole serum was found to have been associated with the lipids. Only 10-20% of the label was covalently bound to apolipoproteins, predominantly to the apolipoproteins A-I and A-II. 4. The interaction of taurocholate with high-density lipoprotein has been confirmed by density gradient centrifugation using 14C-labelled taurcholate. It is assumed that the interaction of taurocholate with high-density lipoprotein is physiologically of significance.", "contents": "Bile salt binding to serum components. Taurocholate incorporation into high-density lipoprotein revealed by photoaffinity labelling. 1. Photoaffinity labelling of human serum albumin with the sodium salts of (3 beta-azido-7 alpha,12 alpha-dihydroxy-5 beta-cholan-24-oyl)-2-amino[2(-3)H (N)]ethanesulfonic acid, (7,7-azo-3 alpha,12 alpha-dihydroxy-5 beta-cholan-24-oyl)-2-amino[2(-3)H (N)]ethanesulfonic acid and (11 zeta-azido-12-oxo-3 alpha,7 alpha-dihydroxy-5 beta-cholan-24-oyl)-2-amino[2(-3)H (N)]ethanesulfonic acid resulted, in each case, in a considerable covalent incorporation of radioactivity into the protein. 2. Photoaffinity labelling of whole serum, obtained from fasting test persons, revealed with all three photolabile derivatives of taurocholate at the physiological concentration of 2.1 microM the incorporation of radioactivity not only into albumin but also into high-density lipoprotein, as demonstrated by density gradient centrifugation and by immunological characterization. 3. The bulk of radioactivity incorporated into high-density lipoprotein by photoaffinity labelling of whole serum was found to have been associated with the lipids. Only 10-20% of the label was covalently bound to apolipoproteins, predominantly to the apolipoproteins A-I and A-II. 4. The interaction of taurocholate with high-density lipoprotein has been confirmed by density gradient centrifugation using 14C-labelled taurcholate. It is assumed that the interaction of taurocholate with high-density lipoprotein is physiologically of significance."}
{"id": "PMID:230037", "title": "High number of high-affinity binding sites for (-)-[3H]dihydroalprenolol on isolated hamster brown-fat cells. A study of the beta-adrenergic receptors.", "content": "The beta-adrenergic receptors of hamster brown adipocytes have been characterised by binding of the radioactive ligand (-)-[3H]dihydroalprenolol, directly to isolated intact cells in suspension. The brown fat cell contains 57,000 specific and saturable binding sites which have a dissociation constant (Kd) for [3H]dihydroalprenolol of 1.4 nM as determined by Scatchard analysis. The kinetically derived Kd, determined from forward and reverse rate constants, is 5 nM. Both of these values are in agreement with the dissociation constant (Kd = 2.2 nM) for alprenolol, determined from competition studies with [3H]dihydroalprenolol in these cells. Beta-adrenergic agonists competed for the specific binding sites with a typical beta 1-adrenergic specificity. The order of potency of agonists agrees well with the ability of these agents to stimulate respiration in isolated brown adipocytes: 50% stimulation of respiration occurs with apparently less than 10% occupancy of binding sites. Both the high affinity and high number of specific binding sites of [3H]dihydroalprenolol in brown fat cells presumably reflect the generally accepted dominating role of catecholamines in the regulation of brown fat metabolism and non-shivering thermogenesis.", "contents": "High number of high-affinity binding sites for (-)-[3H]dihydroalprenolol on isolated hamster brown-fat cells. A study of the beta-adrenergic receptors. The beta-adrenergic receptors of hamster brown adipocytes have been characterised by binding of the radioactive ligand (-)-[3H]dihydroalprenolol, directly to isolated intact cells in suspension. The brown fat cell contains 57,000 specific and saturable binding sites which have a dissociation constant (Kd) for [3H]dihydroalprenolol of 1.4 nM as determined by Scatchard analysis. The kinetically derived Kd, determined from forward and reverse rate constants, is 5 nM. Both of these values are in agreement with the dissociation constant (Kd = 2.2 nM) for alprenolol, determined from competition studies with [3H]dihydroalprenolol in these cells. Beta-adrenergic agonists competed for the specific binding sites with a typical beta 1-adrenergic specificity. The order of potency of agonists agrees well with the ability of these agents to stimulate respiration in isolated brown adipocytes: 50% stimulation of respiration occurs with apparently less than 10% occupancy of binding sites. Both the high affinity and high number of specific binding sites of [3H]dihydroalprenolol in brown fat cells presumably reflect the generally accepted dominating role of catecholamines in the regulation of brown fat metabolism and non-shivering thermogenesis."}
{"id": "PMID:230038", "title": "Characterization of the membrane-bound inorganic pyrophosphatase in Rhodospirillum rubrum.", "content": "The membrane-bound inorganic pyrophosphatase (EC 3.6.1.1) from Rhodospirillum rubrum has been investigated with the tools of enzyme kinetics, and with two amino acid reagents, N-ethyl-maleimide (MalNET) and 4-chloro-7-nitrobenzofurazan (Nbf-Cl). 1. The concentration of the true substrate, MgPPi, was varied with constant concentrations of free Mg2+ or PPi. It was observed that Mg2+ acted as an activator. 2. Heat inactivation of the enzyme at 62 degrees C was slowed down in the presence of Mg2+. 3. MalNET and Nbf-Cl bind to the enzyme, and inhibit its activity. The effect of both reagents is dependent on the temperature. 4. A model is proposed where the 1:1 complex of Mg2+:PPi acts as substrate and Mg2+ interacts directly with the enzyme as an activator. PPi can bind to the enzyme, but is not hydrolyzed in the uncomplexed form.", "contents": "Characterization of the membrane-bound inorganic pyrophosphatase in Rhodospirillum rubrum. The membrane-bound inorganic pyrophosphatase (EC 3.6.1.1) from Rhodospirillum rubrum has been investigated with the tools of enzyme kinetics, and with two amino acid reagents, N-ethyl-maleimide (MalNET) and 4-chloro-7-nitrobenzofurazan (Nbf-Cl). 1. The concentration of the true substrate, MgPPi, was varied with constant concentrations of free Mg2+ or PPi. It was observed that Mg2+ acted as an activator. 2. Heat inactivation of the enzyme at 62 degrees C was slowed down in the presence of Mg2+. 3. MalNET and Nbf-Cl bind to the enzyme, and inhibit its activity. The effect of both reagents is dependent on the temperature. 4. A model is proposed where the 1:1 complex of Mg2+:PPi acts as substrate and Mg2+ interacts directly with the enzyme as an activator. PPi can bind to the enzyme, but is not hydrolyzed in the uncomplexed form."}
{"id": "PMID:230039", "title": "Glutathione reductase from human erythrocytes. Amino-acid sequence of a major fragment that links the FAD, NADP and interface domains.", "content": "A major CNBr fragment of glutathione reductase, peptide Q [Krohne-Ehrich, G., Schirmer, R.H. & Untucht-Grau, R. (1977) Eur. J. Biochem. 80, 65-71], was further fractionated by trypsin, chymotrypsin, thermolysin and clostripain digestion. The peptides were isolated and most of them were sequenced by solid-phase Edman degradation. The whole peptide Q was sequenced N-terminally up to position 51 by the same technique. A total sequence of 128 amino acids (28% of the whole protein) was obtained and could be localized in the electron density map [Schulz, G.E., Schirmer, R.H., Sachsenheimer, W. & Pai, E.F. (1978) Nature (Lond.) 273, 120-124] from position 259-387. This part of the polypeptide links and participates in all three domains of the flavoenzyme.", "contents": "Glutathione reductase from human erythrocytes. Amino-acid sequence of a major fragment that links the FAD, NADP and interface domains. A major CNBr fragment of glutathione reductase, peptide Q [Krohne-Ehrich, G., Schirmer, R.H. & Untucht-Grau, R. (1977) Eur. J. Biochem. 80, 65-71], was further fractionated by trypsin, chymotrypsin, thermolysin and clostripain digestion. The peptides were isolated and most of them were sequenced by solid-phase Edman degradation. The whole peptide Q was sequenced N-terminally up to position 51 by the same technique. A total sequence of 128 amino acids (28% of the whole protein) was obtained and could be localized in the electron density map [Schulz, G.E., Schirmer, R.H., Sachsenheimer, W. & Pai, E.F. (1978) Nature (Lond.) 273, 120-124] from position 259-387. This part of the polypeptide links and participates in all three domains of the flavoenzyme."}
{"id": "PMID:230040", "title": "Nuclear mutants of Neurospora crassa temperature-sensitive for the synthesis of cytochrome aa3. Mitochondrial protein synthesis and analysis of the polypeptide composition of cytochrome c oxidase.", "content": "Three previously isolated mutants of Neurospora crassa, temperature-sensitive for the production of cytochrome aa3, have been further analyzed. These mutants have a slightly reduced capacity for mitochondrial protein synthesis when grown at 41 degrees C, although this relative deficiency appeared to be no greater than the deficiency in other cytochrome-aa3-deficient mutants. Thermolability studies revealed that the cytochrome c oxidase purified from each of the mutants grown at 23 degrees C is no more sensitive to heat inactivation than the enzyme isolated from wild-type cells. Sodium dodecylsulfate gel electrophoresis of immunoprecipitates obtained from the mitochondria of each of the mutants grown at 23 degrees C, using antiserum directed against holocytochrome c oxidase, indicated that all the subunits of cytochrome c oxidase were present in relative amounts similar to those found in mitochondria from wild-type cultures. However, when the mitochondria from mutant cultures grown at 41 degrees C were examined in the above fashion, only subunits 5 and 6 of the oxidase were detected. Nonetheless, the mitochondrially synthesized subunit 1, 2 and 3 polypeptides could be immunoprecipitated from mitochondria isolated from mutant cells grown at 41 degrees C and labelled with [3H]leucine in medium containing cycloheximide. Although subunits 4 and 7 could not be detected, because a suitable antibody was not available, the fact that five of the seven subunits were present, but not associated with each other, suggested that the genetic defects in these mutants may affect the process of cytochrome c oxidase assembly.", "contents": "Nuclear mutants of Neurospora crassa temperature-sensitive for the synthesis of cytochrome aa3. Mitochondrial protein synthesis and analysis of the polypeptide composition of cytochrome c oxidase. Three previously isolated mutants of Neurospora crassa, temperature-sensitive for the production of cytochrome aa3, have been further analyzed. These mutants have a slightly reduced capacity for mitochondrial protein synthesis when grown at 41 degrees C, although this relative deficiency appeared to be no greater than the deficiency in other cytochrome-aa3-deficient mutants. Thermolability studies revealed that the cytochrome c oxidase purified from each of the mutants grown at 23 degrees C is no more sensitive to heat inactivation than the enzyme isolated from wild-type cells. Sodium dodecylsulfate gel electrophoresis of immunoprecipitates obtained from the mitochondria of each of the mutants grown at 23 degrees C, using antiserum directed against holocytochrome c oxidase, indicated that all the subunits of cytochrome c oxidase were present in relative amounts similar to those found in mitochondria from wild-type cultures. However, when the mitochondria from mutant cultures grown at 41 degrees C were examined in the above fashion, only subunits 5 and 6 of the oxidase were detected. Nonetheless, the mitochondrially synthesized subunit 1, 2 and 3 polypeptides could be immunoprecipitated from mitochondria isolated from mutant cells grown at 41 degrees C and labelled with [3H]leucine in medium containing cycloheximide. Although subunits 4 and 7 could not be detected, because a suitable antibody was not available, the fact that five of the seven subunits were present, but not associated with each other, suggested that the genetic defects in these mutants may affect the process of cytochrome c oxidase assembly."}
{"id": "PMID:230041", "title": "Nucleic acid binding and unfolding properties of ribosomal protein S1 and the derivatives S1-F1 and m1-S1.", "content": "The nucleic acid binding and unwinding properties of wild-type Escherichia coli ribosomal protein S1 have been compared to those of a mutant form and a large trypsin-resistant fragment, both reported recently [J. Mol. Biol. 127, 41-45 (1979) and J. Biol. Chem. 254, 4309-4312 (1979). The mutant (m1-S1) contains 77% and the fragment (S1-F1) 66% of the polypeptide chain length (approximately 600 amino acid residues) of protein S1. The mutant is active in protein synthesis in vitro; the fragment, although retaining one or more of the functional domains of S1, is inactive in protein synthesis. We find that m1-S1 is is almost as effective as S1 in binding to poly(rU), phage MS2 RNA and simian virus 40 (SV40) DNA, and in unfolding poly(rU) and the helical structures present in MS2 RNA and phi X174 viral DNA. S1-F1, however, binds to poly(rU) and denatured SV40 DNA, but not to MS2 RNA. It unfolds neither poly(rU), nor the residual secondary structure of MS2 RNA or phi X174 viral DNA. Thus, there appears to be a correlation between the loss in ability of S1 to unwind RNA and the loss in its ability to function in protein synthesis.", "contents": "Nucleic acid binding and unfolding properties of ribosomal protein S1 and the derivatives S1-F1 and m1-S1. The nucleic acid binding and unwinding properties of wild-type Escherichia coli ribosomal protein S1 have been compared to those of a mutant form and a large trypsin-resistant fragment, both reported recently [J. Mol. Biol. 127, 41-45 (1979) and J. Biol. Chem. 254, 4309-4312 (1979). The mutant (m1-S1) contains 77% and the fragment (S1-F1) 66% of the polypeptide chain length (approximately 600 amino acid residues) of protein S1. The mutant is active in protein synthesis in vitro; the fragment, although retaining one or more of the functional domains of S1, is inactive in protein synthesis. We find that m1-S1 is is almost as effective as S1 in binding to poly(rU), phage MS2 RNA and simian virus 40 (SV40) DNA, and in unfolding poly(rU) and the helical structures present in MS2 RNA and phi X174 viral DNA. S1-F1, however, binds to poly(rU) and denatured SV40 DNA, but not to MS2 RNA. It unfolds neither poly(rU), nor the residual secondary structure of MS2 RNA or phi X174 viral DNA. Thus, there appears to be a correlation between the loss in ability of S1 to unwind RNA and the loss in its ability to function in protein synthesis."}
{"id": "PMID:230042", "title": "Properties of purified calf thymus poly(adenosine diphosphate ribose) polymerase. Comparison of the DNA-independent and the DNA-dependent enzyme.", "content": "The physicochemical properties of the purified calf thymus poly(ADP-ribose) polymerase were investigated. The enzyme purified to homogeneity was shown to contain about 10% DNA on a weight basis and its activity to be DNA independent. After removing this fragment of DNA, called the sDNA fraction, the enzyme becomes DNA dependent. The activity of this enzyme preparation was entirely dependent on, and completely restored by, added calf thymus DNA or sDNA. However, the calf thymus DNA concentration needed was a hundred times higher than that of sDNA. The properties of the two enzyme preparations, DNA independent and DNA dependent, were essentially the same. They both reacted against the specific antibody obtained with the DNA-independent poly(ADP-ribose) polymerase. The pH optimum was around 8; the activity was stimulated by Mg2+, Mn2+ and Ca2+, and inhibited by high ionic strength, p-chloromercuribenzoate, ADP-ribose, AMP and polylysine. Nicotinamide, thymidine and NADP were shown to be competitive inhibitors. The enzymatic activity was stimulated by histone H1 when the ratio of DNA to histone H1 was 2. Histones H2A, H2B, H3 and H4 had little effect on the DNA-independent enzyme activity, but were strongly inhibitory for the DNA-dependent enzyme. This inhibitory effect could be reversed by allowing the DNA-dependent enzyme to react with the sDNA fraction before adding histone subfractions. The apparent Km for NAD of the DNA-dependent poly(ADP-ribose) polymerase was shown to vary with the DNA concentration. It was minimum when the amount of sDNA was 10% of that of the enzyme. The ratio of the apparent Km for sDNA to the enzyme concentration was constant at any enzyme concentration. The minimum estimation of the number of base pairs of sDNA required for maximal activation of one enzyme molecule was 16. For calf thymus DNA, this estimation was of 640. These results suggest that the activation of the enzyme needs the formation of some complex between the protein and a specific part of the DNA. This complex was preserved in the DNA-independent enzyme preparation.", "contents": "Properties of purified calf thymus poly(adenosine diphosphate ribose) polymerase. Comparison of the DNA-independent and the DNA-dependent enzyme. The physicochemical properties of the purified calf thymus poly(ADP-ribose) polymerase were investigated. The enzyme purified to homogeneity was shown to contain about 10% DNA on a weight basis and its activity to be DNA independent. After removing this fragment of DNA, called the sDNA fraction, the enzyme becomes DNA dependent. The activity of this enzyme preparation was entirely dependent on, and completely restored by, added calf thymus DNA or sDNA. However, the calf thymus DNA concentration needed was a hundred times higher than that of sDNA. The properties of the two enzyme preparations, DNA independent and DNA dependent, were essentially the same. They both reacted against the specific antibody obtained with the DNA-independent poly(ADP-ribose) polymerase. The pH optimum was around 8; the activity was stimulated by Mg2+, Mn2+ and Ca2+, and inhibited by high ionic strength, p-chloromercuribenzoate, ADP-ribose, AMP and polylysine. Nicotinamide, thymidine and NADP were shown to be competitive inhibitors. The enzymatic activity was stimulated by histone H1 when the ratio of DNA to histone H1 was 2. Histones H2A, H2B, H3 and H4 had little effect on the DNA-independent enzyme activity, but were strongly inhibitory for the DNA-dependent enzyme. This inhibitory effect could be reversed by allowing the DNA-dependent enzyme to react with the sDNA fraction before adding histone subfractions. The apparent Km for NAD of the DNA-dependent poly(ADP-ribose) polymerase was shown to vary with the DNA concentration. It was minimum when the amount of sDNA was 10% of that of the enzyme. The ratio of the apparent Km for sDNA to the enzyme concentration was constant at any enzyme concentration. The minimum estimation of the number of base pairs of sDNA required for maximal activation of one enzyme molecule was 16. For calf thymus DNA, this estimation was of 640. These results suggest that the activation of the enzyme needs the formation of some complex between the protein and a specific part of the DNA. This complex was preserved in the DNA-independent enzyme preparation."}
{"id": "PMID:230044", "title": "Comparative biochemical, histochemical and autoradiographic studies of Na+/k+-ATPase in the rectum of dragonfly larvae (Odonata, Aeshnidae).", "content": "Na+/K+-ATPase localization in the rectal wall of larval Aeshna cyanea (Insecta, Odonata) was studied with histochemical precipitation techniques and 3H-ouabain autoradiography in conjunction with biochemical measurements of enzyme activities and radiospectrometry of 3H-ouabain binding, respectively. The NPP-strontium and ATP-lead methods led to complete inhibition of Na+/K+-ATPase in this organ and hence to unreliable histochemical results. The 3H-ouabain binding technique revealed sodium pump sites at the basolateral plasma membranes of the absorptive rectal chloride epithelia.", "contents": "Comparative biochemical, histochemical and autoradiographic studies of Na+/k+-ATPase in the rectum of dragonfly larvae (Odonata, Aeshnidae). Na+/K+-ATPase localization in the rectal wall of larval Aeshna cyanea (Insecta, Odonata) was studied with histochemical precipitation techniques and 3H-ouabain autoradiography in conjunction with biochemical measurements of enzyme activities and radiospectrometry of 3H-ouabain binding, respectively. The NPP-strontium and ATP-lead methods led to complete inhibition of Na+/K+-ATPase in this organ and hence to unreliable histochemical results. The 3H-ouabain binding technique revealed sodium pump sites at the basolateral plasma membranes of the absorptive rectal chloride epithelia."}
{"id": "PMID:230045", "title": "The nuclear matrix of slowly and rapidly proliferating liver cells.", "content": "The nuclear matrix of slowly proliferating rat liver is compared with rapidly proliferating regenerating liver and Zajdela ascites hepatoma cells. While no differences are detected in overall ultrastructure, composition or polypeptide profiles of normal liver versus regenerating liver matrices, significant alterations are observed in the polypeptides of Zajdela hepatoma nuclear matrices.", "contents": "The nuclear matrix of slowly and rapidly proliferating liver cells. The nuclear matrix of slowly proliferating rat liver is compared with rapidly proliferating regenerating liver and Zajdela ascites hepatoma cells. While no differences are detected in overall ultrastructure, composition or polypeptide profiles of normal liver versus regenerating liver matrices, significant alterations are observed in the polypeptides of Zajdela hepatoma nuclear matrices."}
{"id": "PMID:230046", "title": "Value of the brain angioscintigraphy in posterior view.", "content": "The results obtained with intravenous brain angioscintigraphy (IBAS) with 99 mTc-DTPA(Sn) are evaluated in 61 patients with clinical suspicion of cerebellar, cerebral or cranial lesions of posterior location or without focal signs or with a previous IBAS in anterior view being normal or of low significance. One hundred patients without demonstrable cerebral or cranial pathology were explored to define the normal characteristics and variation of the IBAS in posteior view. Of the 61 patients with pathology, 45 showed angioscintigraphic alterations. The following angioscintigraphic patterns were found: 1. Perfusion increased, 2. Perfusion diminished, 3. Flip-flop, 4. Mixed pattern, 5. Circulatory arrest, 6. Jugular venous reflux, 7. Normal IBAS associated with an abnormal morphologicall study, 8. Normal IBAS associated with a normal morphological study.", "contents": "Value of the brain angioscintigraphy in posterior view. The results obtained with intravenous brain angioscintigraphy (IBAS) with 99 mTc-DTPA(Sn) are evaluated in 61 patients with clinical suspicion of cerebellar, cerebral or cranial lesions of posterior location or without focal signs or with a previous IBAS in anterior view being normal or of low significance. One hundred patients without demonstrable cerebral or cranial pathology were explored to define the normal characteristics and variation of the IBAS in posteior view. Of the 61 patients with pathology, 45 showed angioscintigraphic alterations. The following angioscintigraphic patterns were found: 1. Perfusion increased, 2. Perfusion diminished, 3. Flip-flop, 4. Mixed pattern, 5. Circulatory arrest, 6. Jugular venous reflux, 7. Normal IBAS associated with an abnormal morphologicall study, 8. Normal IBAS associated with a normal morphological study."}
{"id": "PMID:230047", "title": "Two different primary tumours of the brain in a patient with breast cancer.", "content": "Some reports on multiple primary brain tumours have been published. When one or more tumours are found in brain scintigraphy they are often supposed to be metastases. Further investigations may thus be given up, especially if the patient has or has had a malignant tumour in some other part of the body. In this report a case is described where the patient began to have cerebral symptoms two years after she had been operated for breast cancer. In the scintigraphy a tumour was found in both brain hemispheres. The tumours were regarded as metastases. But when the patient died in a geriatric hospital it was recognized from the autopsy that one tumour was a meningioma and the other a glioblastoma multiforme.", "contents": "Two different primary tumours of the brain in a patient with breast cancer. Some reports on multiple primary brain tumours have been published. When one or more tumours are found in brain scintigraphy they are often supposed to be metastases. Further investigations may thus be given up, especially if the patient has or has had a malignant tumour in some other part of the body. In this report a case is described where the patient began to have cerebral symptoms two years after she had been operated for breast cancer. In the scintigraphy a tumour was found in both brain hemispheres. The tumours were regarded as metastases. But when the patient died in a geriatric hospital it was recognized from the autopsy that one tumour was a meningioma and the other a glioblastoma multiforme."}
{"id": "PMID:230048", "title": "Renal prostaglandins: relationship to the development of blood pressure and concentrating capacity in pre-term and full term healthy infants.", "content": "The relationships between urinary prostaglandins (PGs)E2 and F2 alpha and the postnatal development of blood pressure and renal concentrating capacity were investigated in 14 pre-term and 32 full term healthy infants. Mean PGE2 and PGF2 alpha excretion was 18.9 and 10.1 ng/h/1.73 m2, respectively, in pre-term infant. In full term infants mean urinary PGE2 was significantly lower (13.4 ng/h/1.73 m2) and PGF2 alpha significantly higher (22.2 ng/h/1.73 m2). The decrease of the PGE2/PGF2 alpha ratio (P less than 0.001) was accompanied by an increase in blood pressure. High PGE2 levels in pre-term infants were inversely correlated with urinary cAMP excretion. A decreasing PGE2/PGF2 alpha ratio in full term infants was associated with increasing urinary osmolality. After intranasal administration of antidiuretic hormone (DDAVP) in 8 full term infants the increase in urinary osmolality and cAMP excretion was accompanied by a drop in PGE2 excretion to less than half the basal values. These findings suggests that the postnatal changes in urinary PG excretion are associated with a concomittant increase in blood pressure and in the concentrating capacity of the neonatal kidney.", "contents": "Renal prostaglandins: relationship to the development of blood pressure and concentrating capacity in pre-term and full term healthy infants. The relationships between urinary prostaglandins (PGs)E2 and F2 alpha and the postnatal development of blood pressure and renal concentrating capacity were investigated in 14 pre-term and 32 full term healthy infants. Mean PGE2 and PGF2 alpha excretion was 18.9 and 10.1 ng/h/1.73 m2, respectively, in pre-term infant. In full term infants mean urinary PGE2 was significantly lower (13.4 ng/h/1.73 m2) and PGF2 alpha significantly higher (22.2 ng/h/1.73 m2). The decrease of the PGE2/PGF2 alpha ratio (P less than 0.001) was accompanied by an increase in blood pressure. High PGE2 levels in pre-term infants were inversely correlated with urinary cAMP excretion. A decreasing PGE2/PGF2 alpha ratio in full term infants was associated with increasing urinary osmolality. After intranasal administration of antidiuretic hormone (DDAVP) in 8 full term infants the increase in urinary osmolality and cAMP excretion was accompanied by a drop in PGE2 excretion to less than half the basal values. These findings suggests that the postnatal changes in urinary PG excretion are associated with a concomittant increase in blood pressure and in the concentrating capacity of the neonatal kidney."}
{"id": "PMID:230049", "title": "Hepatitis types A, B, and non A--non B in childhood.", "content": "199 children with acute hepatitis hospitalized between 1968 and 1978 were tested for serological markers of hepatitis A and B infection. In 24 out of 28 HBsAg-positive patients, hepatitis B infection was diagnosed because of the disappearance of the antigen during convalescence. The histories of the 171 HBsAg-negative children suggested acute hepatitis A infection in 69% of the patients. This diagnosis could be confirmed in 110 of the 116 tested cases (95%) by a more than fourfold increase in the anti-HAV titer or  by detection of anti-HAV of the IgM class. In the 55 HBsAg-negative patients without epidemiological clues as to the type of hepatitis, 40 children exhibited anti-HAV which could be related to acute A infection in 21 out of 22 tested cases. At least 11 patients had to be classified as having nonn A--non B infection. The results indicate that a combination of evaluation of the patient's history and selected serological tests will permit a fast preliminary diagnosis. This is important in the clinical management of patients and protection of contacts with immunoglobulin.", "contents": "Hepatitis types A, B, and non A--non B in childhood. 199 children with acute hepatitis hospitalized between 1968 and 1978 were tested for serological markers of hepatitis A and B infection. In 24 out of 28 HBsAg-positive patients, hepatitis B infection was diagnosed because of the disappearance of the antigen during convalescence. The histories of the 171 HBsAg-negative children suggested acute hepatitis A infection in 69% of the patients. This diagnosis could be confirmed in 110 of the 116 tested cases (95%) by a more than fourfold increase in the anti-HAV titer or  by detection of anti-HAV of the IgM class. In the 55 HBsAg-negative patients without epidemiological clues as to the type of hepatitis, 40 children exhibited anti-HAV which could be related to acute A infection in 21 out of 22 tested cases. At least 11 patients had to be classified as having nonn A--non B infection. The results indicate that a combination of evaluation of the patient's history and selected serological tests will permit a fast preliminary diagnosis. This is important in the clinical management of patients and protection of contacts with immunoglobulin."}
{"id": "PMID:230050", "title": "Development of children with early cytomegalovirus infection.", "content": "To find out whether cytomegalovirus (CMV) infection during the first months of life influences child development, developmental assessment at the age of 2 years was performed on 116 Finnish children chosen at random in a maternity hospital and followed from birth for the occurrence of CMV infection. Two of the children had congenital infection and 39 were infected after birth but before the age of 6 months. Another five children were infected between the ages of 6 and 12 months, and 70 remained non-infected. The developmental assessment, based principally on the Denver Development Screening Test (DDST), included 7 items for gross motor skills, 6 items for fine motor skills, and 4 items for language development. Significantly more perinatally infected children (7/39) were delayed in speech, compared with the non-infected children (3/70). Furthermore, some items assessing fine motor development were passed better by the non-infected than the perinatally infected children, but the difference in total score was not significant. The performance of the two children with congenital CMV infection did not differ from that of the non-infected children.", "contents": "Development of children with early cytomegalovirus infection. To find out whether cytomegalovirus (CMV) infection during the first months of life influences child development, developmental assessment at the age of 2 years was performed on 116 Finnish children chosen at random in a maternity hospital and followed from birth for the occurrence of CMV infection. Two of the children had congenital infection and 39 were infected after birth but before the age of 6 months. Another five children were infected between the ages of 6 and 12 months, and 70 remained non-infected. The developmental assessment, based principally on the Denver Development Screening Test (DDST), included 7 items for gross motor skills, 6 items for fine motor skills, and 4 items for language development. Significantly more perinatally infected children (7/39) were delayed in speech, compared with the non-infected children (3/70). Furthermore, some items assessing fine motor development were passed better by the non-infected than the perinatally infected children, but the difference in total score was not significant. The performance of the two children with congenital CMV infection did not differ from that of the non-infected children."}
{"id": "PMID:230052", "title": "Pseudohypoparathyroidism type II and anticonvulsant rickets.", "content": "A patient treated with anticonvulsants showed hypocalcemia and hyperphosphatemia in association with increased serum parathyroid hormone, reduced serum 25-hydroxy D3, diminished response in phosphorus excretion to exogenous parathyroid hormone and normal response in cyclic AMP excretion. Oral administration of Vitamin D3 resulted in normalization of serum 25-hydroxy D3, calcium, and phosphorus. At this stage, phosphorus excretion after parathyroid hormone returned to normal. These findings suggest that the patient had pseudohypoparathyroidism type II with anti-convulsant medication as a complicating factor.", "contents": "Pseudohypoparathyroidism type II and anticonvulsant rickets. A patient treated with anticonvulsants showed hypocalcemia and hyperphosphatemia in association with increased serum parathyroid hormone, reduced serum 25-hydroxy D3, diminished response in phosphorus excretion to exogenous parathyroid hormone and normal response in cyclic AMP excretion. Oral administration of Vitamin D3 resulted in normalization of serum 25-hydroxy D3, calcium, and phosphorus. At this stage, phosphorus excretion after parathyroid hormone returned to normal. These findings suggest that the patient had pseudohypoparathyroidism type II with anti-convulsant medication as a complicating factor."}
{"id": "PMID:230053", "title": "Neurophysiological comparison of dendritic cable properties in adolescent, middle-aged, and senescent rats.", "content": "Relative dendritic atrophy has been reported in hippocampal granule cells of senescent (25 month) as compared to young (3 month) rats. An electrophysiological study of synaptic response waveform was un;ertaken to determine whether these anatomical changes have physiological correlates of functional significance to the integrative capacity of the granule cells. The variable of interest was the rist time of the extracellularly recorded population synaptic response because this parameter (under appropriate conditions) has been shown to reflect relative electrotonic distance of active synapses from the spike generating zone located near the cell body. By selectively stimulating small subsets of perforant path fibers along its medio-lateral axis, synapses at increasing distances from the soma may be activated and the response waveform recorded. Systematic observations were made on both hemispheres of 3 adolescent (2 months), three middle-aged (12 months), and 3 senescent (28 months) rats. There were no significant differences in the mean, variance, or range of the frequency distributions of synaptic response rise times. However, the medians of the distributions revealed a small shift towards lower values with advanced age. Although the latter finding is consistent with the anatomical changes, the magnitude of the differences were so small as to make their functional significance dubious.", "contents": "Neurophysiological comparison of dendritic cable properties in adolescent, middle-aged, and senescent rats. Relative dendritic atrophy has been reported in hippocampal granule cells of senescent (25 month) as compared to young (3 month) rats. An electrophysiological study of synaptic response waveform was un;ertaken to determine whether these anatomical changes have physiological correlates of functional significance to the integrative capacity of the granule cells. The variable of interest was the rist time of the extracellularly recorded population synaptic response because this parameter (under appropriate conditions) has been shown to reflect relative electrotonic distance of active synapses from the spike generating zone located near the cell body. By selectively stimulating small subsets of perforant path fibers along its medio-lateral axis, synapses at increasing distances from the soma may be activated and the response waveform recorded. Systematic observations were made on both hemispheres of 3 adolescent (2 months), three middle-aged (12 months), and 3 senescent (28 months) rats. There were no significant differences in the mean, variance, or range of the frequency distributions of synaptic response rise times. However, the medians of the distributions revealed a small shift towards lower values with advanced age. Although the latter finding is consistent with the anatomical changes, the magnitude of the differences were so small as to make their functional significance dubious."}
{"id": "PMID:230059", "title": "Meal induced increase in serum triglycerides has no effect on lymphocyte response to mitogens.", "content": "The effect of a standardized heavy meal on the lymphocyte transformations induced by phytohaemagglutinin (PHA), concanavalin A (Con A) and PPD tuberculin was studied. The meal significantly increased the serum triglycerides (P less than 0.01), while it had no effect on cholesterol or high density lipoprotein-cholesterol levels. The increase in serum triglycerides did not affect lymphocyte transformation induced by phytohaemagglutinin or concanavalin A in whole blood microcultures. A slight decrease was observed when lymphocytes were stimulated with one out of three concentrations of PPD tuberculin (P less than 0.05). However, there was no correlation with the increase of triglycerides and decrease in lymphocyte transformation. Our observation shows that physiological changes in serum triglycerides do not affect the capacity of lymphocytes to respond to mitogenic stimulation, and the whole blood micromethod for lymphocyte stimulation to screen the capacity of cell-mediated immunity does not depend on the meal schedule of the patients.", "contents": "Meal induced increase in serum triglycerides has no effect on lymphocyte response to mitogens. The effect of a standardized heavy meal on the lymphocyte transformations induced by phytohaemagglutinin (PHA), concanavalin A (Con A) and PPD tuberculin was studied. The meal significantly increased the serum triglycerides (P less than 0.01), while it had no effect on cholesterol or high density lipoprotein-cholesterol levels. The increase in serum triglycerides did not affect lymphocyte transformation induced by phytohaemagglutinin or concanavalin A in whole blood microcultures. A slight decrease was observed when lymphocytes were stimulated with one out of three concentrations of PPD tuberculin (P less than 0.05). However, there was no correlation with the increase of triglycerides and decrease in lymphocyte transformation. Our observation shows that physiological changes in serum triglycerides do not affect the capacity of lymphocytes to respond to mitogenic stimulation, and the whole blood micromethod for lymphocyte stimulation to screen the capacity of cell-mediated immunity does not depend on the meal schedule of the patients."}
{"id": "PMID:230060", "title": "Lipid and carbohydrate metabolism in uraemia.", "content": "Lipid and carbohydrate metabolism variables were studied in twenty-eight patients with chronic renal failure (mean GFR 7.7 +/- 2.5 ml/min) and uraemic symptoms. 71% of the patients had hypertriglyceridaemia (greater than or equal to 2.2 mmol/l). Total serum cholesterol was normal while VLDL cholesterol was high and alpha-lipoprotein cholesterol was low. The fractional elimination rate of Intralipid was low and inversely correlated to serum triglyceride levels. Intravenous glucose tolerance was reduced with normal or slightly increased fasting blood glucose and insulin values before and during the test. Serum triglycerides were correlated to plasma insulin but not to residual renal function or serum urea levels. The cause of hypertriglyceridaemia and lowering of alpha-Lp cholesterol is not unequivocally clear. Present evidence indicate that retarded catabloism of triglyceride-rich lipoproteins is important but accentuated release of triglyceride-rich lipoproteins may have occurred in a number of cases. The commonly used treatment with beta-blocking agents for hypertension in chronic renal failure may accentuate certain of the metabolic responses in uraemia.", "contents": "Lipid and carbohydrate metabolism in uraemia. Lipid and carbohydrate metabolism variables were studied in twenty-eight patients with chronic renal failure (mean GFR 7.7 +/- 2.5 ml/min) and uraemic symptoms. 71% of the patients had hypertriglyceridaemia (greater than or equal to 2.2 mmol/l). Total serum cholesterol was normal while VLDL cholesterol was high and alpha-lipoprotein cholesterol was low. The fractional elimination rate of Intralipid was low and inversely correlated to serum triglyceride levels. Intravenous glucose tolerance was reduced with normal or slightly increased fasting blood glucose and insulin values before and during the test. Serum triglycerides were correlated to plasma insulin but not to residual renal function or serum urea levels. The cause of hypertriglyceridaemia and lowering of alpha-Lp cholesterol is not unequivocally clear. Present evidence indicate that retarded catabloism of triglyceride-rich lipoproteins is important but accentuated release of triglyceride-rich lipoproteins may have occurred in a number of cases. The commonly used treatment with beta-blocking agents for hypertension in chronic renal failure may accentuate certain of the metabolic responses in uraemia."}
{"id": "PMID:230061", "title": "Glucose tolerance, plasma insulin and alpha-lipoproteins in young male myocardial infarction survivors compared with controls matched on serum cholesterol concentration.", "content": "In order to identify metabolic risk factors other than hypercholesterolaemia, all cases of acute myocardial infarction, diagnosed in males aged under 40 years, were studied over a period of 6 years in G\u00f6teborg, Sweden. Twenty out of twenty-four patients who were alive at the time of the study were compared with forty controls matched for serum cholesterol concentration. A previous report has noted lower apolipoprotein A (apoA) and a higher alpha-lipoprotein triglyceride concentration in these young myocardial infarction patients compared with the matched controls. Basal blood glucose, oral glucose tolerance and plasma insulin levels did not differ between the patients and controls, i.e. decreased glucose tolerance and elevated plasma insulin levels were not found to be additional risk factors for myocardial infarction in young males if serum cholesterol concentration was taken into consideration. This finding could be explained by the fact that patients and controls were all high cholesterol individuals and a difference between the patients and the general population is still possible. Low apoA was a risk factor independent of serum cholesterol as well as glucose intolerance and elevated plasma insulin levels.", "contents": "Glucose tolerance, plasma insulin and alpha-lipoproteins in young male myocardial infarction survivors compared with controls matched on serum cholesterol concentration. In order to identify metabolic risk factors other than hypercholesterolaemia, all cases of acute myocardial infarction, diagnosed in males aged under 40 years, were studied over a period of 6 years in G\u00f6teborg, Sweden. Twenty out of twenty-four patients who were alive at the time of the study were compared with forty controls matched for serum cholesterol concentration. A previous report has noted lower apolipoprotein A (apoA) and a higher alpha-lipoprotein triglyceride concentration in these young myocardial infarction patients compared with the matched controls. Basal blood glucose, oral glucose tolerance and plasma insulin levels did not differ between the patients and controls, i.e. decreased glucose tolerance and elevated plasma insulin levels were not found to be additional risk factors for myocardial infarction in young males if serum cholesterol concentration was taken into consideration. This finding could be explained by the fact that patients and controls were all high cholesterol individuals and a difference between the patients and the general population is still possible. Low apoA was a risk factor independent of serum cholesterol as well as glucose intolerance and elevated plasma insulin levels."}
{"id": "PMID:230067", "title": "Input-output properties of motor unit responses in muscles stretched by imposed displacements of the monkey wrist.", "content": "Reflex responses are \"servo-like\" where the output is graded with the input or are \"triggered\" where the output is independent of input once an input threshold is exceeded. Imposed displacements of monkey or human upper limb joints result in prolonged EMG output in the muscles stretched by the displacements. The longer-latency portions of the prolonged output have been variously reported to be servo-like or to be triggered in nature. In monkeys and humans, angular wrist displacements imposed by step loads result in three peaks (M1, M2 and M3) in the gross EMG recorded from the stretched muscles. Each gross EMG peak largely results from the firing of a separately-responding subpopulation of single motor units (SMUs). We studied the responses of SMUs to loads that were presented to the monkeys in a random order as to magnitude, duration and onset time. Average response histograms were constructed for the SMU responses for individual step load magnitudes. Averages were also constructed for the simultaneously-recorded gross EMG responses for each step load magnitude. The input parameters used were the initial velocity of displacement or the magnitude of step load, while the output was taken as the probability of firing/millisecond/presentation above baseline for the SMUs or the area under the response peaks above baseline for gross EMG. The results establish: 1) That it is not possible to unambiguously determine the input-output properties of the responses to imposed displacements utilizing the analysis of gress EMG activity due to the response characteristics of the various subpopulations of motor units contributing to the gross response. 2) That the SMU activity during all of the peak intervals is monotonically graded with increases in magnitude of the step load or the initial velocity of displacement. Hence, the long-latency portions of the EMG responses are servo-like in nature and are not preprogrammed or triggered responses. 3) That the gain (output/input) of the gross EMG responses almost entirely reflects the variation in the number of motoneurons recruited by changes in magnitude of the step loads rather than variation in the firing rates of motoneurons during the reflex responses.", "contents": "Input-output properties of motor unit responses in muscles stretched by imposed displacements of the monkey wrist. Reflex responses are \"servo-like\" where the output is graded with the input or are \"triggered\" where the output is independent of input once an input threshold is exceeded. Imposed displacements of monkey or human upper limb joints result in prolonged EMG output in the muscles stretched by the displacements. The longer-latency portions of the prolonged output have been variously reported to be servo-like or to be triggered in nature. In monkeys and humans, angular wrist displacements imposed by step loads result in three peaks (M1, M2 and M3) in the gross EMG recorded from the stretched muscles. Each gross EMG peak largely results from the firing of a separately-responding subpopulation of single motor units (SMUs). We studied the responses of SMUs to loads that were presented to the monkeys in a random order as to magnitude, duration and onset time. Average response histograms were constructed for the SMU responses for individual step load magnitudes. Averages were also constructed for the simultaneously-recorded gross EMG responses for each step load magnitude. The input parameters used were the initial velocity of displacement or the magnitude of step load, while the output was taken as the probability of firing/millisecond/presentation above baseline for the SMUs or the area under the response peaks above baseline for gross EMG. The results establish: 1) That it is not possible to unambiguously determine the input-output properties of the responses to imposed displacements utilizing the analysis of gress EMG activity due to the response characteristics of the various subpopulations of motor units contributing to the gross response. 2) That the SMU activity during all of the peak intervals is monotonically graded with increases in magnitude of the step load or the initial velocity of displacement. Hence, the long-latency portions of the EMG responses are servo-like in nature and are not preprogrammed or triggered responses. 3) That the gain (output/input) of the gross EMG responses almost entirely reflects the variation in the number of motoneurons recruited by changes in magnitude of the step loads rather than variation in the firing rates of motoneurons during the reflex responses."}
{"id": "PMID:230068", "title": "Role of ACTH on the cytomorphology of testes of the immature rat.", "content": "The male gametogenic development of the immature rat shows inhibitory effect by the exogenous infusion of ACTH (0.25 IU and 0.50 IU; i.p.). Seminiferous tubular degeneration, Leydig cell atrophy and Sertoli cell regression are very conspicuous in the dosage of 0.50 IU ACTH (i.p.). Cytometrical and histological evidence confirms that ACTH could be inhibited by FSH during male gametogenic development which leads to cellular degeneration of testes in the immature rat.", "contents": "Role of ACTH on the cytomorphology of testes of the immature rat. The male gametogenic development of the immature rat shows inhibitory effect by the exogenous infusion of ACTH (0.25 IU and 0.50 IU; i.p.). Seminiferous tubular degeneration, Leydig cell atrophy and Sertoli cell regression are very conspicuous in the dosage of 0.50 IU ACTH (i.p.). Cytometrical and histological evidence confirms that ACTH could be inhibited by FSH during male gametogenic development which leads to cellular degeneration of testes in the immature rat."}
{"id": "PMID:230069", "title": "Early changes of cyclic nucleotide levels in a mitogenic reaction in the rat mesentery.", "content": "By measuring simultaneously cAMP and cGMP we found a biphasic time course with regard to cGMP and the cGMP/cAMP ratio very early in a mitogenic reaction in vivo. This is a new finding.", "contents": "Early changes of cyclic nucleotide levels in a mitogenic reaction in the rat mesentery. By measuring simultaneously cAMP and cGMP we found a biphasic time course with regard to cGMP and the cGMP/cAMP ratio very early in a mitogenic reaction in vivo. This is a new finding."}
{"id": "PMID:230070", "title": "Effects of dosage and cadmium pretreatment on the binding of cadmium in rat bile.", "content": "The effects of dosage and of cadmium pretreatment on the binding of cadmium in rat bile were studied. With increasing dose a higher cumulative biliary excretion of Cd was observed and a higher percentage of the Cd was excreted in a low-molecular-weight form. On the other hand, after cadmium pretreatment, a decrease in the cumulative biliary excretion of cadmium was observed but a greater percentage of that excreted into the bile was bound to high molecular weight compounds.", "contents": "Effects of dosage and cadmium pretreatment on the binding of cadmium in rat bile. The effects of dosage and of cadmium pretreatment on the binding of cadmium in rat bile were studied. With increasing dose a higher cumulative biliary excretion of Cd was observed and a higher percentage of the Cd was excreted in a low-molecular-weight form. On the other hand, after cadmium pretreatment, a decrease in the cumulative biliary excretion of cadmium was observed but a greater percentage of that excreted into the bile was bound to high molecular weight compounds."}
{"id": "PMID:230071", "title": "Sex-dependent action of prenatal fractionated X-irradiation in the mouse. Biochemical findings.", "content": "X-irradiation of pregnant NMRI-mice on gestational days 11-13 with 3 x 10.5 Gy increased postnatal mortality of the female offspring only. Weights, protein content and acetylcholinesterase, as well as Na,K-ATPase activities in the brains of all treated offspring, were changed. There were, however, no differences between females and males with respect to these parameters.", "contents": "Sex-dependent action of prenatal fractionated X-irradiation in the mouse. Biochemical findings. X-irradiation of pregnant NMRI-mice on gestational days 11-13 with 3 x 10.5 Gy increased postnatal mortality of the female offspring only. Weights, protein content and acetylcholinesterase, as well as Na,K-ATPase activities in the brains of all treated offspring, were changed. There were, however, no differences between females and males with respect to these parameters."}
{"id": "PMID:230072", "title": "Changes in beta-2 adrenergic receptor sensitivity with maturation of erythroid progenitor cells.", "content": "Erythroid burst forming units (BFU-E) were much more sensitive to the beta-2 selective adrenergic drug, salbutamol, than erythroid colony forming units (CFU-E) in an in vitro study of erythroid progenitor cells.", "contents": "Changes in beta-2 adrenergic receptor sensitivity with maturation of erythroid progenitor cells. Erythroid burst forming units (BFU-E) were much more sensitive to the beta-2 selective adrenergic drug, salbutamol, than erythroid colony forming units (CFU-E) in an in vitro study of erythroid progenitor cells."}
{"id": "PMID:230073", "title": "Control of the hypothalamus-pituitary-adrenal axis in young and older rats injected with thyroxine.", "content": "Administration of T4 on alternate weeks for 30 weeks at a dosage which does not alter body weight depresses basal serum corticosterone levels in older rats (575 days), but not in young animals (260 days). Similar serum corticosterone response to HPA axis stimulation occurs regardless of age or T4 injection.", "contents": "Control of the hypothalamus-pituitary-adrenal axis in young and older rats injected with thyroxine. Administration of T4 on alternate weeks for 30 weeks at a dosage which does not alter body weight depresses basal serum corticosterone levels in older rats (575 days), but not in young animals (260 days). Similar serum corticosterone response to HPA axis stimulation occurs regardless of age or T4 injection."}
{"id": "PMID:230094", "title": "Fusion of L line daughter cells in the presence of Sendai virus.", "content": "Sendai virus induces the fusion of daughter cells in a population of murine fibroblasts (L cell line). Mitosis and the ensuing fusion of two daughter cells has been observed by means of time-lapse cinemicrography. The paper documents two types of cell fusion: a) two daughter cells become completely separated at the end of the mitosis, and fuse only after a certain period of time, or b) the daughter cells remain attached through a narrow bridge of cytoplasm which persists between the cells as a consequence of incomplete cytokinesis. Widening of the cytoplasmic bridge ultimately results in the fusion of cells. The interval between the termination of mitosis and the fusion ranged from 45 to 60 min. The biological significance of the resulting polyploid cells is discussed.", "contents": "Fusion of L line daughter cells in the presence of Sendai virus. Sendai virus induces the fusion of daughter cells in a population of murine fibroblasts (L cell line). Mitosis and the ensuing fusion of two daughter cells has been observed by means of time-lapse cinemicrography. The paper documents two types of cell fusion: a) two daughter cells become completely separated at the end of the mitosis, and fuse only after a certain period of time, or b) the daughter cells remain attached through a narrow bridge of cytoplasm which persists between the cells as a consequence of incomplete cytokinesis. Widening of the cytoplasmic bridge ultimately results in the fusion of cells. The interval between the termination of mitosis and the fusion ranged from 45 to 60 min. The biological significance of the resulting polyploid cells is discussed."}
{"id": "PMID:230101", "title": "Effect of colchicine on PGE1 stimulation of cAMP1 formation in human lymphoblastoid and normal lymphocytes.", "content": "PGE1 increased cAMP level in human lymphoblastoid cells (RPMI 1788) after 5-60 min of incubation at 37 degrees C. A gradual decrease of cAMP concentration was found at the later time intervals. Colchicine significantly potentiated the stimulatory effect of PGE1, although it did not have any effect on cAMP level in control lymphoblastoid cells. The maximal effect of colchicine on PGE1 stimulation of cAMP formation was at the 0.1-1.0 microM level. Human lymphocytes also responded with increased cAMP formation to colchicine addition. In contrast, no stimulatory effect of colchicine was found in human granulocytes.", "contents": "Effect of colchicine on PGE1 stimulation of cAMP1 formation in human lymphoblastoid and normal lymphocytes. PGE1 increased cAMP level in human lymphoblastoid cells (RPMI 1788) after 5-60 min of incubation at 37 degrees C. A gradual decrease of cAMP concentration was found at the later time intervals. Colchicine significantly potentiated the stimulatory effect of PGE1, although it did not have any effect on cAMP level in control lymphoblastoid cells. The maximal effect of colchicine on PGE1 stimulation of cAMP formation was at the 0.1-1.0 microM level. Human lymphocytes also responded with increased cAMP formation to colchicine addition. In contrast, no stimulatory effect of colchicine was found in human granulocytes."}
{"id": "PMID:230102", "title": "Guanyl nucleotide regulation of hormonally-responsive adenylyl cyclases.", "content": "A large number of hormones and neurotransmitters activate adenylyl cyclase [ATP, pyrophosphate lyase (cyclizing; EC 4.6.1.1.)] catalyzing the formation of cAMP and PPi from ATP in the presence of Mg2+. The cAMP formed is in turn responsible for eliciting the physiological responses of these hormones and neurotransmitters. In addition to hormones and neurotransmitters, fluoride ion, cholera toxin and guanyl nucleotides (GTP and GTP analogs such as GTP gamma S and GMP-P(NH)P) also stimulate adenylyl cyclase activity (Perkins, 1974; Birnbaumer, 1977; Gill, 1977). It has become evident that hormonally-responsive adenylyl cyclase is a multi-component system consisting of at least 3 physically distinct units. The first is the hormone receptor containing a specific site for a given hormone. The second is the catalytic moiety (C component) of adenylyl cyclase bearing the site responsible for catalysis of the cyclizing reaction. The third is the guanyl nucleotide regulatory subunit (G component) which binds guanyl nucleotide. Recently, a GTPase activity has been found to be associated with the G component of adenylyl cyclase (Cassel and Selinger, 1976; Cassel et al., 1977a, b; Lambert et al., 1979). In this review we will present information on the regulation of hormonally-responsive adenylyl cyclases. This is not intended to be a comprehensive review of the literature. Rather, it represents our views on the current status of the regulation of cAMP formation.", "contents": "Guanyl nucleotide regulation of hormonally-responsive adenylyl cyclases. A large number of hormones and neurotransmitters activate adenylyl cyclase [ATP, pyrophosphate lyase (cyclizing; EC 4.6.1.1.)] catalyzing the formation of cAMP and PPi from ATP in the presence of Mg2+. The cAMP formed is in turn responsible for eliciting the physiological responses of these hormones and neurotransmitters. In addition to hormones and neurotransmitters, fluoride ion, cholera toxin and guanyl nucleotides (GTP and GTP analogs such as GTP gamma S and GMP-P(NH)P) also stimulate adenylyl cyclase activity (Perkins, 1974; Birnbaumer, 1977; Gill, 1977). It has become evident that hormonally-responsive adenylyl cyclase is a multi-component system consisting of at least 3 physically distinct units. The first is the hormone receptor containing a specific site for a given hormone. The second is the catalytic moiety (C component) of adenylyl cyclase bearing the site responsible for catalysis of the cyclizing reaction. The third is the guanyl nucleotide regulatory subunit (G component) which binds guanyl nucleotide. Recently, a GTPase activity has been found to be associated with the G component of adenylyl cyclase (Cassel and Selinger, 1976; Cassel et al., 1977a, b; Lambert et al., 1979). In this review we will present information on the regulation of hormonally-responsive adenylyl cyclases. This is not intended to be a comprehensive review of the literature. Rather, it represents our views on the current status of the regulation of cAMP formation."}
{"id": "PMID:230103", "title": "Regulatory functions of protein multisite phosphorylation.", "content": "In recent years it has become apparent that an increasing number of proteins can be phosphorylated at several different sites. In this article protein multisite phosphorylation is discussed with reference to the enzymes glycogen synthase, pyruvate dehydrogenase, and phosphorylase kinase. Each of these enzymes contains three or more different phosphorylation sites on one or more subunits. Activation and inactivation of the enzymes appear to correlate quite well with phosphorylation of a few key sites on the protein. The other phosphorylation sites may influence other kinetic properties of the enzymes or regulate the rates of dephosphorylation of the key sites by the appropriate phosphatase. Thus, multisite phosphorylation may represent an important mechanism for regulating several functions of complex proteins.", "contents": "Regulatory functions of protein multisite phosphorylation. In recent years it has become apparent that an increasing number of proteins can be phosphorylated at several different sites. In this article protein multisite phosphorylation is discussed with reference to the enzymes glycogen synthase, pyruvate dehydrogenase, and phosphorylase kinase. Each of these enzymes contains three or more different phosphorylation sites on one or more subunits. Activation and inactivation of the enzymes appear to correlate quite well with phosphorylation of a few key sites on the protein. The other phosphorylation sites may influence other kinetic properties of the enzymes or regulate the rates of dephosphorylation of the key sites by the appropriate phosphatase. Thus, multisite phosphorylation may represent an important mechanism for regulating several functions of complex proteins."}
{"id": "PMID:230104", "title": "Central control of lactogenic receptors in liver membranes: effect of hypothalamic deafferentation.", "content": "The regulation by the central nervous system of a lactogenic receptor, present in the rat liver, was studied. The receptor, which is present in very low concentration or absent in the male rat, can be induced by anterior hypothalamic deafferentation, resulting in a typically female level of the receptor in lesioned male animals. Our observations indicate an important role of the brain in regulation of peripheral lactogenic receptors.", "contents": "Central control of lactogenic receptors in liver membranes: effect of hypothalamic deafferentation. The regulation by the central nervous system of a lactogenic receptor, present in the rat liver, was studied. The receptor, which is present in very low concentration or absent in the male rat, can be induced by anterior hypothalamic deafferentation, resulting in a typically female level of the receptor in lesioned male animals. Our observations indicate an important role of the brain in regulation of peripheral lactogenic receptors."}
{"id": "PMID:230105", "title": "Preliminary characterization of in vitro synthesized hypothalamic precursor ACTH/beta-endorphin-like material.", "content": "We have previously shown that cultured bovine pituitary or hypothalamic cells incorporate 3H-labeled amino acids into high molecular weight glycoproteins containing the antigenic determinants of both corticotropin (ACTH) and beta-endorphin. We now report resolution of this 3H-labeled ACTH/beta-endorphin-like material into two predominant size classes upon SDS polyacrylamide-gel electrophoresis with apparent molecular weights (Mr) of 41 500 +/- 1600 and 36 000 +/- 1100. Isoelectric focusing revealed these components to be basic proteins with apparent isoelectric points greater than 8.5. Overnight trypsinization generated a 3H-labeled fragment comigrating with synthetic beta-lipotropin (61-69) [beta-endorphin (1-9)] upon paper electrophoresis which was immunoprecipitable with antibody directed against the corresponding synthetic fragment. Limited trypsinization of bovine immunoreactive ACTH/beta-endorphin extracted from freshly obtained bovine hypothalamic and anterior pituitary tissue, generated fragments which possessed ACTH bioreactivity. Both bovine pituitary and hypothalamic derived material are similar with respect to these foregoing physiochemical parameters and appear to be larger than the reported forms in mouse pituitary.", "contents": "Preliminary characterization of in vitro synthesized hypothalamic precursor ACTH/beta-endorphin-like material. We have previously shown that cultured bovine pituitary or hypothalamic cells incorporate 3H-labeled amino acids into high molecular weight glycoproteins containing the antigenic determinants of both corticotropin (ACTH) and beta-endorphin. We now report resolution of this 3H-labeled ACTH/beta-endorphin-like material into two predominant size classes upon SDS polyacrylamide-gel electrophoresis with apparent molecular weights (Mr) of 41 500 +/- 1600 and 36 000 +/- 1100. Isoelectric focusing revealed these components to be basic proteins with apparent isoelectric points greater than 8.5. Overnight trypsinization generated a 3H-labeled fragment comigrating with synthetic beta-lipotropin (61-69) [beta-endorphin (1-9)] upon paper electrophoresis which was immunoprecipitable with antibody directed against the corresponding synthetic fragment. Limited trypsinization of bovine immunoreactive ACTH/beta-endorphin extracted from freshly obtained bovine hypothalamic and anterior pituitary tissue, generated fragments which possessed ACTH bioreactivity. Both bovine pituitary and hypothalamic derived material are similar with respect to these foregoing physiochemical parameters and appear to be larger than the reported forms in mouse pituitary."}
{"id": "PMID:230106", "title": "Immunization against poliomyelitis: risk/benefit/cost in a changing context.", "content": "Benefit/risk factors in immunization against poliomyelitis are examined from the viewpoint of the relative risk and efficacy of killed and live poliovirus vaccines in the currently changing contexts of poliomyelitis prevalence in developed and developing countries. Risk factors include virus of vaccine origin gaining access to the CNS, and failure of the vaccine to immunize. Data are presented to illustrate the degree to which the respective risks occur in developed and developing countries. The ultimate elimination of risk by eradication of wild and vaccine virus from the population is discussed.", "contents": "Immunization against poliomyelitis: risk/benefit/cost in a changing context. Benefit/risk factors in immunization against poliomyelitis are examined from the viewpoint of the relative risk and efficacy of killed and live poliovirus vaccines in the currently changing contexts of poliomyelitis prevalence in developed and developing countries. Risk factors include virus of vaccine origin gaining access to the CNS, and failure of the vaccine to immunize. Data are presented to illustrate the degree to which the respective risks occur in developed and developing countries. The ultimate elimination of risk by eradication of wild and vaccine virus from the population is discussed."}
{"id": "PMID:230108", "title": "Antibody to poliovirus in older children and young adults in Israel and the use of poliovaccines for the immunization of the seronegatives.", "content": "This report represents preliminary results of a more extensive study which is presently being carried out in Israel. The main aims of this study were twofold: (1) to carry out a survey of the state of immunity of children of various ages and of teenagers to the three poliovirus types and (2) to compare the antibody response of the seronegatives to the two kinds of presently available poliovaccines, the oral poliovaccine (O. P. V., Savin Vaccine) and the inactivated poliovaccine (I. P. V., Salk Vaccine).", "contents": "Antibody to poliovirus in older children and young adults in Israel and the use of poliovaccines for the immunization of the seronegatives. This report represents preliminary results of a more extensive study which is presently being carried out in Israel. The main aims of this study were twofold: (1) to carry out a survey of the state of immunity of children of various ages and of teenagers to the three poliovirus types and (2) to compare the antibody response of the seronegatives to the two kinds of presently available poliovaccines, the oral poliovaccine (O. P. V., Savin Vaccine) and the inactivated poliovaccine (I. P. V., Salk Vaccine)."}
{"id": "PMID:230110", "title": "Poliomyelitis epidemic in the Netherlands, 1978.", "content": "Some provisional data are given of the polio-epidemic in The Netherlands in 1978. Contrary to previous outbreaks, the present epidemic did not only affect areas with low vaccination acceptance rates, cases were also reported from many municipalities with acceptance rates of 90% and over. The epidemic caused by type 1 started mid-April 1978 in the centre of the country. Up to 1st November 110 cases were reported from a belt running from South-West (Zeeland) to North-East (Overijssel). Only one death occurred among the 80 paralyzed cases. The epidemic exclusively struck a population of some Protestant denominations which mostly reject vaccination on religious grounds. The majority of the cases belong to a population of about 66,000 individuals under the age of 27, who were not vaccinated on religious grounds. No case of polio, however, was found in about 384,000 individuals under the age of 27 who has not been vaccinated on other than religious grounds. No case of polio occurred in the vaccinated (inactivated poliovaccine) population. The exclusive spread of the epidemic in a poorly vaccinated but coherent population, whose members are thoroughy mixed in an extremely well vaccinated population (annual acceptance rate about 95%) is discussed.", "contents": "Poliomyelitis epidemic in the Netherlands, 1978. Some provisional data are given of the polio-epidemic in The Netherlands in 1978. Contrary to previous outbreaks, the present epidemic did not only affect areas with low vaccination acceptance rates, cases were also reported from many municipalities with acceptance rates of 90% and over. The epidemic caused by type 1 started mid-April 1978 in the centre of the country. Up to 1st November 110 cases were reported from a belt running from South-West (Zeeland) to North-East (Overijssel). Only one death occurred among the 80 paralyzed cases. The epidemic exclusively struck a population of some Protestant denominations which mostly reject vaccination on religious grounds. The majority of the cases belong to a population of about 66,000 individuals under the age of 27, who were not vaccinated on religious grounds. No case of polio, however, was found in about 384,000 individuals under the age of 27 who has not been vaccinated on other than religious grounds. No case of polio occurred in the vaccinated (inactivated poliovaccine) population. The exclusive spread of the epidemic in a poorly vaccinated but coherent population, whose members are thoroughy mixed in an extremely well vaccinated population (annual acceptance rate about 95%) is discussed."}
{"id": "PMID:230111", "title": "Poliovirus antibodies in age groups: an assessment of obligatory vaccination in Belgium.", "content": "Since 1967, compulsory oral vaccination before 2 years of age has been nearly the only form of poliovaccination practiced in Belgium, and there have been almost no cases of polio. In recent sera from 2,225 Belgians, 2 year olds lacked demonstrable seroneutralizing antibody, in 31% for type 1, in 8% for type 2, and in 21% for type 3. The lack of antibodies grew as the children reached 11--12 years, at which age 65% lacked antibody for type 1, 15% for type 2, and 54% for type 3; only 19% had antibodies against all types. It is argued that this decline of antibodies is not due to insufficient vaccination in former years, but is a strong example of the waning of vaccine-acquired serum antibody. Antibody rates went up after age 12. The highest rates of types 1 and 3 antibodies were seen at age 20--59. There was some decrease of antibody after 60 years. Mean antibody titers paralleled positivity rates. Results of two laboratories studying different populations with different standard techniques were similar. The data support revaccination at school entrance.", "contents": "Poliovirus antibodies in age groups: an assessment of obligatory vaccination in Belgium. Since 1967, compulsory oral vaccination before 2 years of age has been nearly the only form of poliovaccination practiced in Belgium, and there have been almost no cases of polio. In recent sera from 2,225 Belgians, 2 year olds lacked demonstrable seroneutralizing antibody, in 31% for type 1, in 8% for type 2, and in 21% for type 3. The lack of antibodies grew as the children reached 11--12 years, at which age 65% lacked antibody for type 1, 15% for type 2, and 54% for type 3; only 19% had antibodies against all types. It is argued that this decline of antibodies is not due to insufficient vaccination in former years, but is a strong example of the waning of vaccine-acquired serum antibody. Antibody rates went up after age 12. The highest rates of types 1 and 3 antibodies were seen at age 20--59. There was some decrease of antibody after 60 years. Mean antibody titers paralleled positivity rates. Results of two laboratories studying different populations with different standard techniques were similar. The data support revaccination at school entrance."}
{"id": "PMID:230113", "title": "Herpes simplex virus: benefit versus risk factors in immunization.", "content": "Vaccines developed against herpes simplex viruses (HSV) should be effective in two respects: (i) they should prevent primary infections and virus latency and (ii) if applied to individuals with recurrent herpetic lesions they should reduce the number of recurrences or at least mitigate the symptoms. The efficiency of vaccines which are presently available will be reviewed. Problems associated with the possible use of live attenuated or inactivated HSV vaccines will be discussed. Comparative aspects to existing vaccines against other herpes group viruses will be stressed.", "contents": "Herpes simplex virus: benefit versus risk factors in immunization. Vaccines developed against herpes simplex viruses (HSV) should be effective in two respects: (i) they should prevent primary infections and virus latency and (ii) if applied to individuals with recurrent herpetic lesions they should reduce the number of recurrences or at least mitigate the symptoms. The efficiency of vaccines which are presently available will be reviewed. Problems associated with the possible use of live attenuated or inactivated HSV vaccines will be discussed. Comparative aspects to existing vaccines against other herpes group viruses will be stressed."}
{"id": "PMID:230114", "title": "Antibody and cell-mediated immunity to a DNA free herpes simplex subunit vaccine.", "content": "The immunogenicity of a DNA free herpes simplex subunit vaccine was evaluated in chimpanzees and rabbits. The results clearly demonstrate that 1 injection of 3 micrograms/kg elicited antibodies as well as cell-mediated immunity in all the animals studied. These antibodies persisted for at least 6 months. Furthermore the vaccine also protected 50% of the animals against an experimental infection and reduced the rate of latent infection in nervous sensory ganglia.", "contents": "Antibody and cell-mediated immunity to a DNA free herpes simplex subunit vaccine. The immunogenicity of a DNA free herpes simplex subunit vaccine was evaluated in chimpanzees and rabbits. The results clearly demonstrate that 1 injection of 3 micrograms/kg elicited antibodies as well as cell-mediated immunity in all the animals studied. These antibodies persisted for at least 6 months. Furthermore the vaccine also protected 50% of the animals against an experimental infection and reduced the rate of latent infection in nervous sensory ganglia."}
{"id": "PMID:230116", "title": "Guillain-Barr\u00e9 syndrome associated with Epstein-Barr virus in a cytomegalovirus-negative patient.", "content": "Epstein-Barr virus and cytomegalovirus have both been associated with Guillain-Barr\u00e9 syndrome after antibody investigations in several patients. In the teenage female patient in this present report, Guillain-Barr\u00e9 syndrome following infectious mononucleosis was associated with sero-conversion against Epstein-Barr virus but not cytomegalovirus. The findings are consistent with the hypothesis that Epstein-Barr virus might be an etiological agent for the Guillain-Barr\u00e9 syndrome and that infection with cytomegalovirus is not a requisite for the syndrome.", "contents": "Guillain-Barr\u00e9 syndrome associated with Epstein-Barr virus in a cytomegalovirus-negative patient. Epstein-Barr virus and cytomegalovirus have both been associated with Guillain-Barr\u00e9 syndrome after antibody investigations in several patients. In the teenage female patient in this present report, Guillain-Barr\u00e9 syndrome following infectious mononucleosis was associated with sero-conversion against Epstein-Barr virus but not cytomegalovirus. The findings are consistent with the hypothesis that Epstein-Barr virus might be an etiological agent for the Guillain-Barr\u00e9 syndrome and that infection with cytomegalovirus is not a requisite for the syndrome."}
{"id": "PMID:230118", "title": "[Granulosa cell and thecacell tumors in 25 cases (author's transl)].", "content": "Granulosa cell tumors are derived from specific ovarion stroma and have the ability to produce hormones. In the 25 cases of granulosa cell tumors no concommitant endometrial carcinoma was found. Because of the varying degree of malignancy tumors which contain granulosa cells must be differentiated from pure theca cell tumors. Granulosa cell tumors are frequently malignant. Theca cell tumors are benign. The treatment of granulosa cell tumors is fundamentally the same as that of epithelial cancers of the ovary. The treatment of theca cell tumors is conservative.", "contents": "[Granulosa cell and thecacell tumors in 25 cases (author's transl)]. Granulosa cell tumors are derived from specific ovarion stroma and have the ability to produce hormones. In the 25 cases of granulosa cell tumors no concommitant endometrial carcinoma was found. Because of the varying degree of malignancy tumors which contain granulosa cells must be differentiated from pure theca cell tumors. Granulosa cell tumors are frequently malignant. Theca cell tumors are benign. The treatment of granulosa cell tumors is fundamentally the same as that of epithelial cancers of the ovary. The treatment of theca cell tumors is conservative."}
{"id": "PMID:230119", "title": "[Hidradenoma of the vulva (author's transl)].", "content": "Five cases of hidradenoma of the vulva are reported. The differential diagnosis is discussed. Painstaking microscopic diagnosis is very important since the hidradenoma may be confused with an adenocarcinoma. Local excision of the small tumour is the only treatment necessary.", "contents": "[Hidradenoma of the vulva (author's transl)]. Five cases of hidradenoma of the vulva are reported. The differential diagnosis is discussed. Painstaking microscopic diagnosis is very important since the hidradenoma may be confused with an adenocarcinoma. Local excision of the small tumour is the only treatment necessary."}
{"id": "PMID:230123", "title": "[Genetic determination of the response of the mouse hypothalamo-hypophyseo-adrenal system to cold and immobilization stress].", "content": "Peculiarities of the hypothalamo-pituitary-adrenal system (HPAS) reaction in mice of 8 inbred strains to a stress effect of the immoblization and of cold have been studied and a comparison of the effect with the reaction of the adrenal cortex to its direct stimulator--ACTH have been carried out. As a result of the study of the resting level of 11-hydroxycorticosteroids in peripheral plasma of inbred mice significant interstrain differences were found. A positive correlation between resting corticosteroids level and the reaction of HPAS to the stress in mouse strains under study was found, but none of them correlated with the reactivity of the adrenal cortex to ACTH.", "contents": "[Genetic determination of the response of the mouse hypothalamo-hypophyseo-adrenal system to cold and immobilization stress]. Peculiarities of the hypothalamo-pituitary-adrenal system (HPAS) reaction in mice of 8 inbred strains to a stress effect of the immoblization and of cold have been studied and a comparison of the effect with the reaction of the adrenal cortex to its direct stimulator--ACTH have been carried out. As a result of the study of the resting level of 11-hydroxycorticosteroids in peripheral plasma of inbred mice significant interstrain differences were found. A positive correlation between resting corticosteroids level and the reaction of HPAS to the stress in mouse strains under study was found, but none of them correlated with the reactivity of the adrenal cortex to ACTH."}
{"id": "PMID:230124", "title": "Construction and characterization of a recombinant plasmid encoding the gene for the thymidine kinase of Herpes simplex type 1 virus.", "content": "We have constructed a hybrid plasmid by insertion of the thymidine kinase (TK) gene of Herpes simplex virus (HSV) type I at the BamHI site on Escherichia coli plasmid pBR322. The restriction endonuclease cleavage site map for the viral DNA fragment was determined for ten nucleases, and the insert in the recombinant plasmid has the same restriction nuclease digestion pattern as bona fide viral DNA. This result indicates that the plasmid contains an accurate copy of the viral DNA. The viral TK gene carried on the plasmid can be introduced into mammalian cells where it is expressed. This source of DNA with a selectable marker should be of considerable practical use in gene-transfer experiments in mammalian cells.", "contents": "Construction and characterization of a recombinant plasmid encoding the gene for the thymidine kinase of Herpes simplex type 1 virus. We have constructed a hybrid plasmid by insertion of the thymidine kinase (TK) gene of Herpes simplex virus (HSV) type I at the BamHI site on Escherichia coli plasmid pBR322. The restriction endonuclease cleavage site map for the viral DNA fragment was determined for ten nucleases, and the insert in the recombinant plasmid has the same restriction nuclease digestion pattern as bona fide viral DNA. This result indicates that the plasmid contains an accurate copy of the viral DNA. The viral TK gene carried on the plasmid can be introduced into mammalian cells where it is expressed. This source of DNA with a selectable marker should be of considerable practical use in gene-transfer experiments in mammalian cells."}
{"id": "PMID:230128", "title": "Hepatic prolyl hydroxylase and collagen synthesis in patients with alcoholic liver disease.", "content": "Hepatic prolyl hydroxylase activity and collagen synthesis were measured in patients with alcoholic liver disease to determine the feasibility of using the enzyme prolyl hydroxylase as a marker of hepatic fibrogenesis. Alcoholic patients with liver histopathology consistent with normal, steatosis, alcoholic hepatitis, early cirrhosis, or advanced cirrhosis were analysed for liver prolyl hydroxylase activity and in vitro collagen synthesis. Prolyl hydroxylase activity and the rate of in vitro collagen synthesis were correlated when these parameters were measured in samples of the same liver biopsy. Mean prolyl hydroxylase activity was significantly raised in all groups of alcoholic patients with alcoholic liver disease, except those with steatosis, when compared with alcoholic patients with normal morphology. Alcoholic patients with early cirrhosis had enzyme activity (mean +/- SE: 1.367 +/-0.162 mU/mg protein) significantly raised over all other groups. Mean enzyme activity was less raised (0.985 +/- 0.097 mU/mg protein) in patients with advanced cirrhosis. The percentage of collagen synthesis in patients with early or advanced cirrhosis was also raised compared with alcoholic patients with normal morphology. Prolyl hydroxylase activity and the rate of collagen synthesis are significantly correlated (r=0.62). These findings suggest that hepatic prolyl hydroxylase activity is a useful indicator of hepatic fibrogenesis and its measurement on available liver biopsy tissue should be a potent diagnostic tool reflecting active fibrogenesis and predicting progression of alcoholic liverdisease.", "contents": "Hepatic prolyl hydroxylase and collagen synthesis in patients with alcoholic liver disease. Hepatic prolyl hydroxylase activity and collagen synthesis were measured in patients with alcoholic liver disease to determine the feasibility of using the enzyme prolyl hydroxylase as a marker of hepatic fibrogenesis. Alcoholic patients with liver histopathology consistent with normal, steatosis, alcoholic hepatitis, early cirrhosis, or advanced cirrhosis were analysed for liver prolyl hydroxylase activity and in vitro collagen synthesis. Prolyl hydroxylase activity and the rate of in vitro collagen synthesis were correlated when these parameters were measured in samples of the same liver biopsy. Mean prolyl hydroxylase activity was significantly raised in all groups of alcoholic patients with alcoholic liver disease, except those with steatosis, when compared with alcoholic patients with normal morphology. Alcoholic patients with early cirrhosis had enzyme activity (mean +/- SE: 1.367 +/-0.162 mU/mg protein) significantly raised over all other groups. Mean enzyme activity was less raised (0.985 +/- 0.097 mU/mg protein) in patients with advanced cirrhosis. The percentage of collagen synthesis in patients with early or advanced cirrhosis was also raised compared with alcoholic patients with normal morphology. Prolyl hydroxylase activity and the rate of collagen synthesis are significantly correlated (r=0.62). These findings suggest that hepatic prolyl hydroxylase activity is a useful indicator of hepatic fibrogenesis and its measurement on available liver biopsy tissue should be a potent diagnostic tool reflecting active fibrogenesis and predicting progression of alcoholic liverdisease."}
{"id": "PMID:230129", "title": "Vitamin D metabolism in acute and chronic cholestasis.", "content": "To study the effects of acute and chronic cholestasis on vitamin D metabolism we investigated six cases of acute extrahepatic obstructive jaundice and eight cases of primary biliary cirrhosis (PBC) (three supplemented with vitamin D). Plasma 25-hydroxyvitamin D (25OHD) was low in the patients with PBC unsupplemented with vitamin D but normal in obstructive jaundice. None of the patients with PBC showed radiological or histological evidence of osteomalacia. In PBC, dietary intake of vitamin D was low but response to ultra-violet irradiation of the skin was normal even in those with a considerably raised serum bilirubin. Patients with PBC or obstructive jaundice had low levels of 25 hydroxyvitamin D binding protein which correlated with the serum albumin. The half-life of intravenously injected (3)H vitamin D(3) ((3)HD(3)) and the subsequent production of (3)H 25OHD were normal in all the patients with obstructive jaundice and in most with PBC. The two patients with PBC who produced less (3)H 25OHD than expected were receiving vitamin D supplements. The urinary tritium ((3)H) excretion after the injection of (3)HD(3) correlated with the serum bilirubin. After the injection of (3)H 25OHD(3) the urinary excretion of (3)H was minimal and did not correlate with the serum bilirubin, suggesting that the radioactivity appearing in the urine after the (3)H vitamin D(3) injection was associated with vitamin D metabolites other than 25OHD. Factors contributing to the low plasma 25OHD in primary biliary cirrhosis may be a low dietary intake of vitamin D, inadequate exposure to ultra-violet light, and a tendency to urinary wastage of vitamin D metabolites.", "contents": "Vitamin D metabolism in acute and chronic cholestasis. To study the effects of acute and chronic cholestasis on vitamin D metabolism we investigated six cases of acute extrahepatic obstructive jaundice and eight cases of primary biliary cirrhosis (PBC) (three supplemented with vitamin D). Plasma 25-hydroxyvitamin D (25OHD) was low in the patients with PBC unsupplemented with vitamin D but normal in obstructive jaundice. None of the patients with PBC showed radiological or histological evidence of osteomalacia. In PBC, dietary intake of vitamin D was low but response to ultra-violet irradiation of the skin was normal even in those with a considerably raised serum bilirubin. Patients with PBC or obstructive jaundice had low levels of 25 hydroxyvitamin D binding protein which correlated with the serum albumin. The half-life of intravenously injected (3)H vitamin D(3) ((3)HD(3)) and the subsequent production of (3)H 25OHD were normal in all the patients with obstructive jaundice and in most with PBC. The two patients with PBC who produced less (3)H 25OHD than expected were receiving vitamin D supplements. The urinary tritium ((3)H) excretion after the injection of (3)HD(3) correlated with the serum bilirubin. After the injection of (3)H 25OHD(3) the urinary excretion of (3)H was minimal and did not correlate with the serum bilirubin, suggesting that the radioactivity appearing in the urine after the (3)H vitamin D(3) injection was associated with vitamin D metabolites other than 25OHD. Factors contributing to the low plasma 25OHD in primary biliary cirrhosis may be a low dietary intake of vitamin D, inadequate exposure to ultra-violet light, and a tendency to urinary wastage of vitamin D metabolites."}
{"id": "PMID:230130", "title": "Papaverine stimulation of prostaglandin E2 production by cultured rabbit gastric mucosa.", "content": "Prostaglandins (PGs) are synthesised by gastric mucosa, and have been shown to inhibit gastric acid secretion and ulcer formation in man and experimental animals. Recently exogenous PGs, mainly of the E group, have been used for the treatment of peptic ulcer disease. We therefore searched for a drug that would stimulate endogenous gastric prostaglandin E(2) (PGE(2)) synthesis. Rabbit gastric mucosa slices were cultured for 22 hours at 77 degrees C. PGE(2), measured by radioimmunoassay, was found to be linearly secreted into the culture medium. PGE(2) accumulation in the medium during 22 hours of culture was 7.9+/-0.5 (SE) ng/mg tissue (N=20). Addition of papaverine (100 mu/ml), a cyclic nucleotide phosphodiesterase inhibitor, resulted in a significant increase (250% of control) in PGE(2) accumulation in the medium: 24.3+/-1.8 ng/mg tissue (N=25). Isobutylmethylxanthine (IBMX 100 mug/ml), another phosphodiesterase inhibitor, only slightly increased PGE(2) accumulation, while 8 bromo-cyclic AMP (1 mM) had no effect. Under these conditions IBMX increased by 20-fold mucosal cyclic AMP levels: 3.9+/-0.3 pmol/mg tissue (N=8) as compared with control levels: 0.2+/-0.03 pmol/mg tissue (N=8). Papaverine, however, did not alter mucosal cyclic AMP accumulation. These results indicate that papaverine stimulates PGE(2) production by cultured rabbit gastric mucosa and that this stimulation is not related to the inhibition of phosphodiesterase activity and accumulation of mucosal cyclic AMP. Papaverine induced stimulation of PGE(2) production should be further evaluated regarding its possible beneficial effects in protecting gastric mucosa and in reducing acid secretion in peptic ulcer patients.", "contents": "Papaverine stimulation of prostaglandin E2 production by cultured rabbit gastric mucosa. Prostaglandins (PGs) are synthesised by gastric mucosa, and have been shown to inhibit gastric acid secretion and ulcer formation in man and experimental animals. Recently exogenous PGs, mainly of the E group, have been used for the treatment of peptic ulcer disease. We therefore searched for a drug that would stimulate endogenous gastric prostaglandin E(2) (PGE(2)) synthesis. Rabbit gastric mucosa slices were cultured for 22 hours at 77 degrees C. PGE(2), measured by radioimmunoassay, was found to be linearly secreted into the culture medium. PGE(2) accumulation in the medium during 22 hours of culture was 7.9+/-0.5 (SE) ng/mg tissue (N=20). Addition of papaverine (100 mu/ml), a cyclic nucleotide phosphodiesterase inhibitor, resulted in a significant increase (250% of control) in PGE(2) accumulation in the medium: 24.3+/-1.8 ng/mg tissue (N=25). Isobutylmethylxanthine (IBMX 100 mug/ml), another phosphodiesterase inhibitor, only slightly increased PGE(2) accumulation, while 8 bromo-cyclic AMP (1 mM) had no effect. Under these conditions IBMX increased by 20-fold mucosal cyclic AMP levels: 3.9+/-0.3 pmol/mg tissue (N=8) as compared with control levels: 0.2+/-0.03 pmol/mg tissue (N=8). Papaverine, however, did not alter mucosal cyclic AMP accumulation. These results indicate that papaverine stimulates PGE(2) production by cultured rabbit gastric mucosa and that this stimulation is not related to the inhibition of phosphodiesterase activity and accumulation of mucosal cyclic AMP. Papaverine induced stimulation of PGE(2) production should be further evaluated regarding its possible beneficial effects in protecting gastric mucosa and in reducing acid secretion in peptic ulcer patients."}
{"id": "PMID:230134", "title": "Overnight polygraphic studies of infantile spasms--influence of hormone therapy on sleep states, pulse, respiration and seizure activities.", "content": "The influence of hormone therapy on sleep states, pulse, respiration and seizure activities of infantile spasms was examined by means of overnight sleep polygraphy. Also the correlation between the changes of these parameters and the prognosis was investigated. The results were as follows: 1) In all cases, the awake time of TIB during hormone therapy was longer than before hormone therapy. The reduction of REM sleep time of SPT and lowering of REM density were remarkable during hormone therapy in cases with delayed psychomotor development as compared with cases with a considerable degree of psychomotor development. During hormone therapy, the NREM sleep time of SPT was shortened in cases with ACTH therapy, and prolonged in case with hydrocortisone therapy. 2) During hormone therapy, the pulse rate increased significantly in cases with a considerable degree of psychomotor development, but decreased significantly in cases with delayed psychomotor development. The change of respiratory rate by hormone therapy was not remarkable in all cases. 3) In cases with hypsarhythmic EEG records, the number of spikes decreased drastically by hormone therapy. In the case with EEG record of focal spikes, the number of spikes increased by hormone therapy. From the results mentioned above, the mechanism for effectiveness of hormone therapy and correlation between the administration of hormone therapy and prognosis was discussed.", "contents": "Overnight polygraphic studies of infantile spasms--influence of hormone therapy on sleep states, pulse, respiration and seizure activities. The influence of hormone therapy on sleep states, pulse, respiration and seizure activities of infantile spasms was examined by means of overnight sleep polygraphy. Also the correlation between the changes of these parameters and the prognosis was investigated. The results were as follows: 1) In all cases, the awake time of TIB during hormone therapy was longer than before hormone therapy. The reduction of REM sleep time of SPT and lowering of REM density were remarkable during hormone therapy in cases with delayed psychomotor development as compared with cases with a considerable degree of psychomotor development. During hormone therapy, the NREM sleep time of SPT was shortened in cases with ACTH therapy, and prolonged in case with hydrocortisone therapy. 2) During hormone therapy, the pulse rate increased significantly in cases with a considerable degree of psychomotor development, but decreased significantly in cases with delayed psychomotor development. The change of respiratory rate by hormone therapy was not remarkable in all cases. 3) In cases with hypsarhythmic EEG records, the number of spikes decreased drastically by hormone therapy. In the case with EEG record of focal spikes, the number of spikes increased by hormone therapy. From the results mentioned above, the mechanism for effectiveness of hormone therapy and correlation between the administration of hormone therapy and prognosis was discussed."}
{"id": "PMID:230138", "title": "[The hyper-reactive bronchial system. Pathophysiologic aspects and therapeutic consequences].", "content": "We talk about a hypersensitive bronchial system, when under certain endogen prepositions or exogen influences, upon which a healthy persons reacts hardly or not at all, it comes to a significant raise of the airway resistances. Probably this is the prestadium of a chronic obstructive airway disease, which often occurs with patients suffering from an existant bronchial disease. Therefore it is important for actual clinical practice to discuss those problems, which interfere with the raise of sensitivity of the bronchial airways. The discussion should be based on the actual state of science, because several therapeutic problems and consequences ensue.", "contents": "[The hyper-reactive bronchial system. Pathophysiologic aspects and therapeutic consequences]. We talk about a hypersensitive bronchial system, when under certain endogen prepositions or exogen influences, upon which a healthy persons reacts hardly or not at all, it comes to a significant raise of the airway resistances. Probably this is the prestadium of a chronic obstructive airway disease, which often occurs with patients suffering from an existant bronchial disease. Therefore it is important for actual clinical practice to discuss those problems, which interfere with the raise of sensitivity of the bronchial airways. The discussion should be based on the actual state of science, because several therapeutic problems and consequences ensue."}
{"id": "PMID:230141", "title": "Adrenal-cortical function in patients with medullary carcinoma of the thyroid and pheochromocytoma.", "content": "Medullary carcinoma of the thyroid (MCT) is reported to synthesize ACTH. This ACTH is believed to be responsible for the development of Cushing's syndrome in some patients with MCT. To determine the frequency of occurrence of adrenal cortical overactivity in patients with MCT, we measured plasma cortisol concentration and the urinary excretion of 17-hydroxycorticosteroids, 17-ketosteroids and urinary free cortisol in 22 patients with MCT and 7 patients with MCT plus pheochromocytomas. The patients with MCT and MCT plus pheochromocytoma had similar adrenal cortical function to age and sex matched normal subjects. We conclude that adrenal cortical function is usually normal in patients with MCT.", "contents": "Adrenal-cortical function in patients with medullary carcinoma of the thyroid and pheochromocytoma. Medullary carcinoma of the thyroid (MCT) is reported to synthesize ACTH. This ACTH is believed to be responsible for the development of Cushing's syndrome in some patients with MCT. To determine the frequency of occurrence of adrenal cortical overactivity in patients with MCT, we measured plasma cortisol concentration and the urinary excretion of 17-hydroxycorticosteroids, 17-ketosteroids and urinary free cortisol in 22 patients with MCT and 7 patients with MCT plus pheochromocytomas. The patients with MCT and MCT plus pheochromocytoma had similar adrenal cortical function to age and sex matched normal subjects. We conclude that adrenal cortical function is usually normal in patients with MCT."}
{"id": "PMID:230142", "title": "In vitro studies of the testis: the effect of LH on cyclic nucleotides.", "content": "This study evaluated the relationship between LH, cyclic AMP, cyclic GMP, and testosterone using in vitro incubation of decapsulated rat testes and sampling incubation medium. With added LH (1.0, 5.0, 100, and 500 mIU/ml) there were statistically significant increases in cyclic AMP at 5 mIU/ml or more LH, and progressively greater titers of this nucleotide were produced as LH was increased. For cyclic GMP all levels of added LH caused significant increments in titers of nucleotide; however, peak cyclic GMP concentrations occurred with 5 mIU/ml of LH. The addition of 10(-3) and 10-(4)M 8-bromo-cyclic AMP caused significant increases in testosterone production, while no changes in production of this androgen were found with 10(-3), 10(-4), or 10(-5)M 8-bromo-cyclic GMP. Neither cyclic AMP nor cyclic GMP titers were altered by the addition of 1 to 50 micrograms/ml of testosterone to medium bathing the rat testes. The dose response curves of cyclic AMP and cyclic GMP to LH are different. Progressive increments in added LH cause parallel increases of cyclic AMP and a biphasic change of cyclic GMP, 8-bromo-cyclic GMP does not cause testosterone generation, suggesting that cyclic GMP does not result in androgen synthesis. However, cyclic GMP may be involved in other Leydig cell functions.", "contents": "In vitro studies of the testis: the effect of LH on cyclic nucleotides. This study evaluated the relationship between LH, cyclic AMP, cyclic GMP, and testosterone using in vitro incubation of decapsulated rat testes and sampling incubation medium. With added LH (1.0, 5.0, 100, and 500 mIU/ml) there were statistically significant increases in cyclic AMP at 5 mIU/ml or more LH, and progressively greater titers of this nucleotide were produced as LH was increased. For cyclic GMP all levels of added LH caused significant increments in titers of nucleotide; however, peak cyclic GMP concentrations occurred with 5 mIU/ml of LH. The addition of 10(-3) and 10-(4)M 8-bromo-cyclic AMP caused significant increases in testosterone production, while no changes in production of this androgen were found with 10(-3), 10(-4), or 10(-5)M 8-bromo-cyclic GMP. Neither cyclic AMP nor cyclic GMP titers were altered by the addition of 1 to 50 micrograms/ml of testosterone to medium bathing the rat testes. The dose response curves of cyclic AMP and cyclic GMP to LH are different. Progressive increments in added LH cause parallel increases of cyclic AMP and a biphasic change of cyclic GMP, 8-bromo-cyclic GMP does not cause testosterone generation, suggesting that cyclic GMP does not result in androgen synthesis. However, cyclic GMP may be involved in other Leydig cell functions."}
{"id": "PMID:230149", "title": "Comparative studies of two types of \"spontaneous\" malignant alteration of ST/A mouse lung fibroblasts propagated in vitro.", "content": "Two types of apparently spontaneous malignant alterations of fibroblastlike ST/a mouse lung cells (ST-L cells) grown in vitro are described. One type is characterized by a high tumorigenic potential of the altered cells in nonconditioned syngeneic recipients, a fibroblastlike morphology with cell surface showing very few microvilli by scanning electron-microscopy (SEM), and a growth pattern typical of nontransformed cells. These cells were described as R- cells. The other type is characterized bya low tumorigenic potential in non-conditioned, immunocompetent syngeneic recipients, rounding up of the cells which by SEM showed numerous microvilli on the surface, and a growth pattern typical  of transformed cells. These cells were described as round cells or R+ cells. In immunoincompetent mice, R+ cells readily produced sarcomas, which grew faster than those produced by R- cells. Both types of ST-L cells expressed murine leukemia virus (MuLV) when tested in  a peroxidase anti-p30 plaque test. The concentration of murine leukemia virus envelope glycoprotein (gp70) has previously (5) been shown to be threefold higher in R+ cells compared to R- cells. Furthermore, round-cell transformation was accompanied by the development of crossreacting rejection antigens protective against a secondary shallenge with Ehrlich ascites tumor and with syngeneic dimethylbenzanthracene induced ST/a mouse leukemia (STABAL). A similar protection was obtained by preimmunization with a cloned embryonic feral mouse cell line (SC-1) infected with ST-L virus as well as with virus-free SC-1 cells, suggesting the presence of rejection antigens both of viral (gp70) and nonviral origin.", "contents": "Comparative studies of two types of \"spontaneous\" malignant alteration of ST/A mouse lung fibroblasts propagated in vitro. Two types of apparently spontaneous malignant alterations of fibroblastlike ST/a mouse lung cells (ST-L cells) grown in vitro are described. One type is characterized by a high tumorigenic potential of the altered cells in nonconditioned syngeneic recipients, a fibroblastlike morphology with cell surface showing very few microvilli by scanning electron-microscopy (SEM), and a growth pattern typical of nontransformed cells. These cells were described as R- cells. The other type is characterized bya low tumorigenic potential in non-conditioned, immunocompetent syngeneic recipients, rounding up of the cells which by SEM showed numerous microvilli on the surface, and a growth pattern typical  of transformed cells. These cells were described as round cells or R+ cells. In immunoincompetent mice, R+ cells readily produced sarcomas, which grew faster than those produced by R- cells. Both types of ST-L cells expressed murine leukemia virus (MuLV) when tested in  a peroxidase anti-p30 plaque test. The concentration of murine leukemia virus envelope glycoprotein (gp70) has previously (5) been shown to be threefold higher in R+ cells compared to R- cells. Furthermore, round-cell transformation was accompanied by the development of crossreacting rejection antigens protective against a secondary shallenge with Ehrlich ascites tumor and with syngeneic dimethylbenzanthracene induced ST/a mouse leukemia (STABAL). A similar protection was obtained by preimmunization with a cloned embryonic feral mouse cell line (SC-1) infected with ST-L virus as well as with virus-free SC-1 cells, suggesting the presence of rejection antigens both of viral (gp70) and nonviral origin."}
{"id": "PMID:230150", "title": "Studies on cultured rat Schwann cells. II. Comparison with a rat Schwann cell line.", "content": "Cultured rat Schwann cells do not exhibit the ring-like changes in cell shape previously reported to be induced in the Schwann cell line RN22 by elevation of intracellular cyclic AMP. They do, however, undergo different shape changes on treatment with cholera toxin or low serum concentration. Furthermore, DNA synthesis in the cell line is inhibited by treatment with cholera toxin and unaffected by bovine pituitary extract, though both of these agents stimulate DNA synthesis in normal Schwann cells. Our results, therefore, do not support the hypothesis that elevation of intracellular cyclic AMP is a positive signal for myelination by the Schwann cell. Moreover, they illustrate the need for caution in drawing conclusions about normal cells of the nervous system from studies on neural cell lines.", "contents": "Studies on cultured rat Schwann cells. II. Comparison with a rat Schwann cell line. Cultured rat Schwann cells do not exhibit the ring-like changes in cell shape previously reported to be induced in the Schwann cell line RN22 by elevation of intracellular cyclic AMP. They do, however, undergo different shape changes on treatment with cholera toxin or low serum concentration. Furthermore, DNA synthesis in the cell line is inhibited by treatment with cholera toxin and unaffected by bovine pituitary extract, though both of these agents stimulate DNA synthesis in normal Schwann cells. Our results, therefore, do not support the hypothesis that elevation of intracellular cyclic AMP is a positive signal for myelination by the Schwann cell. Moreover, they illustrate the need for caution in drawing conclusions about normal cells of the nervous system from studies on neural cell lines."}
{"id": "PMID:230158", "title": "Fine structure of a glomus tumor of the tongue and expression of C type virus in its tumor cells.", "content": "A glomus tumor in the tongue of a 29-year-old Japanese male is presented. Ultrastructural examination demonstrated this tumor to be composed of the tumor cells having structural features in common with smooth muscle cells, and mast cells as the less frequent type cell. Moreover, a small number of C type virus particles were found to be in the cytoplasm or in the intercellular spaces. In this communication, besides the detailed description of the morphology of the glomus tumor, the possible involvement of C type virus in processes of tumor formation is discussed.", "contents": "Fine structure of a glomus tumor of the tongue and expression of C type virus in its tumor cells. A glomus tumor in the tongue of a 29-year-old Japanese male is presented. Ultrastructural examination demonstrated this tumor to be composed of the tumor cells having structural features in common with smooth muscle cells, and mast cells as the less frequent type cell. Moreover, a small number of C type virus particles were found to be in the cytoplasm or in the intercellular spaces. In this communication, besides the detailed description of the morphology of the glomus tumor, the possible involvement of C type virus in processes of tumor formation is discussed."}
{"id": "PMID:230159", "title": "Preparation and some properties of a dimeric form (S-S) of horse muscle acylphosphatase.", "content": "The use of sodium selenite as a catalyst in the presence of oxygen was a suitable technique to obtain in good yield an interchain S-S dimeric form of horse muscle acylphosphatase. The dimer so obtained possesses kinetic properties very similar to those of the native enzyme. On the other hand the dimer has shown a generally lower stability in respect of the thermal inactivation, particularly in the acidic environment, to the lyophilization and to the proteolytic attack. As regards the 8 M urea inactivation, the dimer is not able to completely regain its activity by dilution, showing a behaviour quite different from that of the native enzyme.", "contents": "Preparation and some properties of a dimeric form (S-S) of horse muscle acylphosphatase. The use of sodium selenite as a catalyst in the presence of oxygen was a suitable technique to obtain in good yield an interchain S-S dimeric form of horse muscle acylphosphatase. The dimer so obtained possesses kinetic properties very similar to those of the native enzyme. On the other hand the dimer has shown a generally lower stability in respect of the thermal inactivation, particularly in the acidic environment, to the lyophilization and to the proteolytic attack. As regards the 8 M urea inactivation, the dimer is not able to completely regain its activity by dilution, showing a behaviour quite different from that of the native enzyme."}
{"id": "PMID:230155", "title": "The influence of Artobotrys odoratissimus Linn. extracts on phosphatase activity in the uterus of rats.", "content": "The effect of 50% ethanolic and benzene extracts of Artobotrys odoratissimus Linn., a potent antiestrogenic plant on uterine acid and alkaline phosphatase activity has been studied in adult rats. Both the extracts decreased the alkaline phosphatase activity in the uterus of intact and ovariectomized rats (P less than 0.001) but elevated the acid phosphatase activity (P less than 0.001). 50% ethanolic extract acts at low dose levels; however its activity decreases as the dose is increased. Benzene extract showed more consistent dose-response relationship.", "contents": "The influence of Artobotrys odoratissimus Linn. extracts on phosphatase activity in the uterus of rats. The effect of 50% ethanolic and benzene extracts of Artobotrys odoratissimus Linn., a potent antiestrogenic plant on uterine acid and alkaline phosphatase activity has been studied in adult rats. Both the extracts decreased the alkaline phosphatase activity in the uterus of intact and ovariectomized rats (P less than 0.001) but elevated the acid phosphatase activity (P less than 0.001). 50% ethanolic extract acts at low dose levels; however its activity decreases as the dose is increased. Benzene extract showed more consistent dose-response relationship."}
{"id": "PMID:230156", "title": "Reduced beta adrenergic responsiveness in isolated rabbit atria during hypothermia.", "content": "Beta adrenergic agonist isoprenaline (8x10(-6)M) produced a 500% increase in inotropic and 90% increase in the chronotropic responses of isolated rabbit atria at 37 degrees C. On cooling the atria to 23 degrees C, these responses were significantly reduced to 87% and 30% respectively. Similar results were obtained with adrenaline, but isoprenaline was more potent. The positive chronotropic and inotropic responses to isoprenaline were effectively blocked by propranolol and practolol at 37 degrees C whereas at 23 degrees C these beta blockers were unable to block even minor positive responses obtained by isoprenaline at this temperature. On the contrary at 23 degrees C, phenylephrine (alpha adrenergic agonist) produced marked positive chronotropic and inotropic effects indicating enhancement of alpha adrenoceptor activity at lower temperatures. This also suggests that reduced beta receptor activity at lower temperature is not due to a generalised depression of adrenoceptors as a result of hypothermia. Rewarming of atria to 37 degrees C restored the beta adrenoceptor responsiveness to previous level. It appears that ambient temperature is important im maintaining normal beta adrenergic activity of the atria.", "contents": "Reduced beta adrenergic responsiveness in isolated rabbit atria during hypothermia. Beta adrenergic agonist isoprenaline (8x10(-6)M) produced a 500% increase in inotropic and 90% increase in the chronotropic responses of isolated rabbit atria at 37 degrees C. On cooling the atria to 23 degrees C, these responses were significantly reduced to 87% and 30% respectively. Similar results were obtained with adrenaline, but isoprenaline was more potent. The positive chronotropic and inotropic responses to isoprenaline were effectively blocked by propranolol and practolol at 37 degrees C whereas at 23 degrees C these beta blockers were unable to block even minor positive responses obtained by isoprenaline at this temperature. On the contrary at 23 degrees C, phenylephrine (alpha adrenergic agonist) produced marked positive chronotropic and inotropic effects indicating enhancement of alpha adrenoceptor activity at lower temperatures. This also suggests that reduced beta receptor activity at lower temperature is not due to a generalised depression of adrenoceptors as a result of hypothermia. Rewarming of atria to 37 degrees C restored the beta adrenoceptor responsiveness to previous level. It appears that ambient temperature is important im maintaining normal beta adrenergic activity of the atria."}
{"id": "PMID:230167", "title": "Adenosine triphosphatase localization in the branchial heart appendage of Sepia officinalis L. (Cephalopoda).", "content": "Sodium- and potassium-dependent adenosine triphosphatase (Na+--K+-ATPase) has been demonstrated in the branchial heart appendage (pericardial gland) of Sepia officinalis L. by biochemical, cytochemical and autoradiographical methods. The biochemical data indicate the presence of Na+--K+-ATPase, judging from the potassium dependency and, with some restrictions, the inhibition by ouabain. Cytochemically and autoradiographically, the enzyme could be localized on the cytoplasmic surfaces of the lateral plasma membranes and the basal membrane infoldings (basal labyrinth) of the folded epithelium of the branchial heart appendage. The pdocytes of the peripheral zone of the organ reacted negatively. In addition to the Na+--K+-ATPase, a magnesium-activated adenosine triphosphatase (Mg2+-ATPase) was demonstrated in the folded epithelium, localized mainly in the mitochondria but also at the brush border and in the apical intercellular space, whereas a bicarbonate-stimulated ATPase (HCO-3-ATPase) was present only in the mitochondria.", "contents": "Adenosine triphosphatase localization in the branchial heart appendage of Sepia officinalis L. (Cephalopoda). Sodium- and potassium-dependent adenosine triphosphatase (Na+--K+-ATPase) has been demonstrated in the branchial heart appendage (pericardial gland) of Sepia officinalis L. by biochemical, cytochemical and autoradiographical methods. The biochemical data indicate the presence of Na+--K+-ATPase, judging from the potassium dependency and, with some restrictions, the inhibition by ouabain. Cytochemically and autoradiographically, the enzyme could be localized on the cytoplasmic surfaces of the lateral plasma membranes and the basal membrane infoldings (basal labyrinth) of the folded epithelium of the branchial heart appendage. The pdocytes of the peripheral zone of the organ reacted negatively. In addition to the Na+--K+-ATPase, a magnesium-activated adenosine triphosphatase (Mg2+-ATPase) was demonstrated in the folded epithelium, localized mainly in the mitochondria but also at the brush border and in the apical intercellular space, whereas a bicarbonate-stimulated ATPase (HCO-3-ATPase) was present only in the mitochondria."}
{"id": "PMID:230168", "title": "Electron microscopical demonstration of glucose-6-phosphatase in native cryostat sections fixed with glutaraldehyde through semipermeable membranes.", "content": "The cytochemical demonstration of glucose-6-phosphatase (G6Pase) activity in native cryostat sections fixed with glutaraldehyde through semipermeable membranes is superior to conventional methods with regard to exact localization and lack of inactivation and diffusion of the enzyme, together with simultaneous excellent preservation of the tissue fine structure. In rat liver not only hepatocytes but also many bile duct epithelia and endothelia of arterioles and venules show a marked G6Pase activity in the membranes of the endoplasmic reticulum including the nuclear envelope.", "contents": "Electron microscopical demonstration of glucose-6-phosphatase in native cryostat sections fixed with glutaraldehyde through semipermeable membranes. The cytochemical demonstration of glucose-6-phosphatase (G6Pase) activity in native cryostat sections fixed with glutaraldehyde through semipermeable membranes is superior to conventional methods with regard to exact localization and lack of inactivation and diffusion of the enzyme, together with simultaneous excellent preservation of the tissue fine structure. In rat liver not only hepatocytes but also many bile duct epithelia and endothelia of arterioles and venules show a marked G6Pase activity in the membranes of the endoplasmic reticulum including the nuclear envelope."}
{"id": "PMID:230169", "title": "Modification of synaptic facilitation and bursting patterns in Aplysia californica by hyperbaric air.", "content": "We have studied the effects of air pressure to 10 atmospheres absolute on several electrophysiological characteristics of identified neurons in Aplysia californica. These pressures did not affect the resting potential, rates of polarization, amplitude, or duration of action potentials in cell R2. Repetitive stimulation of the right pleurovisceral connective nerve produced a frequency-dependent train of unitary excitatory postsynaptic potentials (PSPs) in cell R15 which showed marked facilitation near the end of the train. The amount of facilitation of the last four PSPs increased significantly (approximately 20%) at 9 ATA air pressure. The amplitude of the first PSP was not altered by pressure. Changes in extracellular [Ca2+] or oxygen tension did not influence these pressure effects. Increases in air pressure also reduced the number of action potentials per burst, burst duration, and interburst interval of cell R15 but left the overall firing frequency unchanged. These results indicate that fundamental neurophysiological processes can be altered by increased gas tensions similar to those confronting animals experiencing narcotic symptoms at less than 300 ft of seawater.", "contents": "Modification of synaptic facilitation and bursting patterns in Aplysia californica by hyperbaric air. We have studied the effects of air pressure to 10 atmospheres absolute on several electrophysiological characteristics of identified neurons in Aplysia californica. These pressures did not affect the resting potential, rates of polarization, amplitude, or duration of action potentials in cell R2. Repetitive stimulation of the right pleurovisceral connective nerve produced a frequency-dependent train of unitary excitatory postsynaptic potentials (PSPs) in cell R15 which showed marked facilitation near the end of the train. The amount of facilitation of the last four PSPs increased significantly (approximately 20%) at 9 ATA air pressure. The amplitude of the first PSP was not altered by pressure. Changes in extracellular [Ca2+] or oxygen tension did not influence these pressure effects. Increases in air pressure also reduced the number of action potentials per burst, burst duration, and interburst interval of cell R15 but left the overall firing frequency unchanged. These results indicate that fundamental neurophysiological processes can be altered by increased gas tensions similar to those confronting animals experiencing narcotic symptoms at less than 300 ft of seawater."}
{"id": "PMID:230170", "title": "Viruses and virus diseases of marine mammals.", "content": "Poxvirus and several serotypes of calicivirus cause recognizable disease in marine mammals. Pox lesions in pinnipeds are raised and proliferative and are seen most frequently after confinement in captivity. In cetaceans, a poxvirus is associated with a much more benign and chronic lesion called a \"tattoo.\" Numerous caliciviruses of differing antigenic types have been isolated from vesicular lesions and aborted fetuses of northern fur seals and California sea lions as well as from clinically normal and orphaned northern elephant seal pups. An adenovirus has been isolated from a sei whale and an enterovirus has been isolated from a gray whale.", "contents": "Viruses and virus diseases of marine mammals. Poxvirus and several serotypes of calicivirus cause recognizable disease in marine mammals. Pox lesions in pinnipeds are raised and proliferative and are seen most frequently after confinement in captivity. In cetaceans, a poxvirus is associated with a much more benign and chronic lesion called a \"tattoo.\" Numerous caliciviruses of differing antigenic types have been isolated from vesicular lesions and aborted fetuses of northern fur seals and California sea lions as well as from clinically normal and orphaned northern elephant seal pups. An adenovirus has been isolated from a sei whale and an enterovirus has been isolated from a gray whale."}
{"id": "PMID:230171", "title": "Poxlike skin lesions in captive caimans.", "content": "Three juvenile captive spectacled caimans (Caiman sclerops) had scattered, gray-white, circular, 1- to 3-mm skin lesions. In one caiman, the lesions were particularly prominent on the phalanges, palpebrae, and integument overlying the maxillae and mandible. Digital biopsy revealed large eosinophilic intracytoplasmic inclusions within epithelial cells. Transmission electron microscopy of lesions from the lower jaw revealed viral particles morphologically similar to poxvirus.", "contents": "Poxlike skin lesions in captive caimans. Three juvenile captive spectacled caimans (Caiman sclerops) had scattered, gray-white, circular, 1- to 3-mm skin lesions. In one caiman, the lesions were particularly prominent on the phalanges, palpebrae, and integument overlying the maxillae and mandible. Digital biopsy revealed large eosinophilic intracytoplasmic inclusions within epithelial cells. Transmission electron microscopy of lesions from the lower jaw revealed viral particles morphologically similar to poxvirus."}
{"id": "PMID:230172", "title": "Herpesvirus-like infection of the venom gland of Siamese cobras.", "content": "The light and electron microscopic appearance of venom glands from two Siamese cobra snakes with a history of production of poor-quality venom was determined. Light microscopy revealed degeneration and necrosis of patches of columnar epithelial cells of glands and infiltration of the subepithelium by inflammatory cells. The lumina contained debris, venom, and necrotic cells. Electron microscopy revealed a deficiency of microvilli on the luminal surfaces of both degenerated and necrotic epithelial cells. The lumina contained fragmented microvilli, coated vesicles containing venom, and degenerated and necrotic cells. Naked and enveloped herpesvirus-like particles were seen in necrotic and ruptured cells. Occasionally, naked herpesvirus-like particles were seen in the nuclei of attached epithelial cells. It was concluded that herpesvirus-like infection of the venom gland was the probable cause of the production of poor-quality venom.", "contents": "Herpesvirus-like infection of the venom gland of Siamese cobras. The light and electron microscopic appearance of venom glands from two Siamese cobra snakes with a history of production of poor-quality venom was determined. Light microscopy revealed degeneration and necrosis of patches of columnar epithelial cells of glands and infiltration of the subepithelium by inflammatory cells. The lumina contained debris, venom, and necrotic cells. Electron microscopy revealed a deficiency of microvilli on the luminal surfaces of both degenerated and necrotic epithelial cells. The lumina contained fragmented microvilli, coated vesicles containing venom, and degenerated and necrotic cells. Naked and enveloped herpesvirus-like particles were seen in necrotic and ruptured cells. Occasionally, naked herpesvirus-like particles were seen in the nuclei of attached epithelial cells. It was concluded that herpesvirus-like infection of the venom gland was the probable cause of the production of poor-quality venom."}
{"id": "PMID:230174", "title": "Analysis of fat-soluble vitamins. XXIII. High performance liquid chromatographic assay for vitamin D in vitamin D3 and multivitamin preparations.", "content": "Vitamin D is determined in preparations containing other fat-soluble vitamins by high performance liquid chromatography (HPLC). The unsaponifiable residue is extracted and separated from interferences by reverse phase chromatography; the fraction corresponding to vitamin D3 is collected and quantitated using normal phase chromatography (amylalcohol-n-hexane as mobile phase) by measuring the vitamin D3 and pre-vitamin D3 peaks at 254 nm. Previtamin D3 content is calculated as vitamin D3 with a conversion factor (determined on the equipment used). Application of the method to vitamin AD3 mixtures in oils gives 98-102% recovery. The reproducibility, using an external standard, is 2-3%, calculated as the coefficient of variation; with an internal standard, the coefficient of variation is 1-1.5%. The method measures potential vitamin D3 content in preparations containing greater than or equal to 200 IU/g in the presence of all known vitamin D3 isomers, vitamin A, and vitamin E.", "contents": "Analysis of fat-soluble vitamins. XXIII. High performance liquid chromatographic assay for vitamin D in vitamin D3 and multivitamin preparations. Vitamin D is determined in preparations containing other fat-soluble vitamins by high performance liquid chromatography (HPLC). The unsaponifiable residue is extracted and separated from interferences by reverse phase chromatography; the fraction corresponding to vitamin D3 is collected and quantitated using normal phase chromatography (amylalcohol-n-hexane as mobile phase) by measuring the vitamin D3 and pre-vitamin D3 peaks at 254 nm. Previtamin D3 content is calculated as vitamin D3 with a conversion factor (determined on the equipment used). Application of the method to vitamin AD3 mixtures in oils gives 98-102% recovery. The reproducibility, using an external standard, is 2-3%, calculated as the coefficient of variation; with an internal standard, the coefficient of variation is 1-1.5%. The method measures potential vitamin D3 content in preparations containing greater than or equal to 200 IU/g in the presence of all known vitamin D3 isomers, vitamin A, and vitamin E."}
{"id": "PMID:230175", "title": "Lactose metabolism by Streptococcus mutans: evidence for induction of the tagatose 6-phosphate pathway.", "content": "Growth on lactose by strains of Streptococcus mutans resulted in the induction of the lactose-phosphoenolpyruvate-phosphotransferase system, phospho-beta-galactosidase, and the enzymes of the tagatose 6-phosphate pathway.", "contents": "Lactose metabolism by Streptococcus mutans: evidence for induction of the tagatose 6-phosphate pathway. Growth on lactose by strains of Streptococcus mutans resulted in the induction of the lactose-phosphoenolpyruvate-phosphotransferase system, phospho-beta-galactosidase, and the enzymes of the tagatose 6-phosphate pathway."}
{"id": "PMID:230176", "title": "Lipolytic activity copurified with the outer membrane of Serratia marcescens.", "content": "Lipase, nuclease, and protease activities could be shown primarily with the purified outer membrane fraction from Serratia marcescens. These activities increased and decreased in the different compartments dependent on the growth phase of the cell culture. Penicillin-hydrolyzing activity was exclusively demonstrated with the outer membrane fraction.", "contents": "Lipolytic activity copurified with the outer membrane of Serratia marcescens. Lipase, nuclease, and protease activities could be shown primarily with the purified outer membrane fraction from Serratia marcescens. These activities increased and decreased in the different compartments dependent on the growth phase of the cell culture. Penicillin-hydrolyzing activity was exclusively demonstrated with the outer membrane fraction."}
{"id": "PMID:230177", "title": "Synthesis and inactivation of carbamyl phosphate synthetase isozymes of Bacillus subtilis during growth and sporulation.", "content": "Pyrimidine-repressible carbamyl phosphate synthetase P was synthesized in parallel with aspartate transcarbamylase during growth of Bacillus subtilis on glucose-nutrient broth. Both enzymes were inactivated at the end of exponential growth, but at different rates and by different mechanisms. Unlike the inactivation of aspartate transcarbamylase, the inactivation of carbamyl phosphate synthetase P was not interrupted by deprivation for oxygen or in a tricarboxylic acid cycle mutant. The arginine-repressible isozyme carbamyl phosphate synthetase A was synthesized in parallel with ornithine transcarbamylase during the stationary phase under these growth conditions. Again, both enzymes were subsequently inactivated, but at different rates and by apparently different mechanisms. The inactivation of carbamyl phosphate synthetase A was not affected in a protease-deficient mutatn the inactivation of ornithine transcarbamylase was greatly slowed.", "contents": "Synthesis and inactivation of carbamyl phosphate synthetase isozymes of Bacillus subtilis during growth and sporulation. Pyrimidine-repressible carbamyl phosphate synthetase P was synthesized in parallel with aspartate transcarbamylase during growth of Bacillus subtilis on glucose-nutrient broth. Both enzymes were inactivated at the end of exponential growth, but at different rates and by different mechanisms. Unlike the inactivation of aspartate transcarbamylase, the inactivation of carbamyl phosphate synthetase P was not interrupted by deprivation for oxygen or in a tricarboxylic acid cycle mutant. The arginine-repressible isozyme carbamyl phosphate synthetase A was synthesized in parallel with ornithine transcarbamylase during the stationary phase under these growth conditions. Again, both enzymes were subsequently inactivated, but at different rates and by apparently different mechanisms. The inactivation of carbamyl phosphate synthetase A was not affected in a protease-deficient mutatn the inactivation of ornithine transcarbamylase was greatly slowed."}
{"id": "PMID:230178", "title": "Isolation of temperature-sensitive pantothenate kinase mutants of Salmonella typhimurium and mapping of the coaA gene.", "content": "Temperature-sensitive pantothenate kinase mutants of Salmonella typhimurium LT2 were selected by using the excretion of pantothenate at the nonpermissive temperature as a screening method. Thermolability of the pathothenate kinase activity in extracts of the mutants was demonstrated. The mutations were mapped at min 89 of the Salmonella chromosome, near rpoB, by transduction. As pantothenate kinase catalyzes the first step in the biosynthesis of coenzyme A from pantothenate, the new genetic locus has been designated coaA.", "contents": "Isolation of temperature-sensitive pantothenate kinase mutants of Salmonella typhimurium and mapping of the coaA gene. Temperature-sensitive pantothenate kinase mutants of Salmonella typhimurium LT2 were selected by using the excretion of pantothenate at the nonpermissive temperature as a screening method. Thermolability of the pathothenate kinase activity in extracts of the mutants was demonstrated. The mutations were mapped at min 89 of the Salmonella chromosome, near rpoB, by transduction. As pantothenate kinase catalyzes the first step in the biosynthesis of coenzyme A from pantothenate, the new genetic locus has been designated coaA."}
{"id": "PMID:230179", "title": "Cytochrome c3 from the sulfate-reducing anaerobe Desulfovibrio africanus Benghazi: purification and properties.", "content": "Cytochrome c3 was purified from Desulfovibrio africanus Benghazi by extraction with alkaline deoxyribonuclease, fractionation with ammonium sulfate, batch elution from carboxymethyl Sephadex followed by chromatography on the same resin, and gel filtration on Sephadex G-75. The preparation was judge homogeneous by a variety of criteria. The molecular weight was determined in an analytical ultracentrifuge, and values between 14,400 and 15,490 were obtained, depending upon the presumed value of partial specific volume. Gel filtration on a calibrated column of Sephadex G-75 gave a value of 14,900 daltons. The amino acid composition was very similar to that observed for the cytochrome from other species of Desulfovibrio, with the exception of increased levels of ThR and PhE. S-Carboxymethylation of the protein before and after heme removal by HgCl2 demonstrated eight Cys molecules involved in heme binding or four heme sites per molecule. Titration with sodium dithionite under N2 gave an electrochemical potential (E' 0) of -276 mV relative to the normal hydrogen electrode. Electrochemical titration of the cytochrome gave a Nernst plot with two linear regions with E' 0 values of -0.376 and -0.534 V. The spectra produced at various potentials exhibited shifts in isosbestic points upon reduction, suggesting changes in conformation during the reaction.", "contents": "Cytochrome c3 from the sulfate-reducing anaerobe Desulfovibrio africanus Benghazi: purification and properties. Cytochrome c3 was purified from Desulfovibrio africanus Benghazi by extraction with alkaline deoxyribonuclease, fractionation with ammonium sulfate, batch elution from carboxymethyl Sephadex followed by chromatography on the same resin, and gel filtration on Sephadex G-75. The preparation was judge homogeneous by a variety of criteria. The molecular weight was determined in an analytical ultracentrifuge, and values between 14,400 and 15,490 were obtained, depending upon the presumed value of partial specific volume. Gel filtration on a calibrated column of Sephadex G-75 gave a value of 14,900 daltons. The amino acid composition was very similar to that observed for the cytochrome from other species of Desulfovibrio, with the exception of increased levels of ThR and PhE. S-Carboxymethylation of the protein before and after heme removal by HgCl2 demonstrated eight Cys molecules involved in heme binding or four heme sites per molecule. Titration with sodium dithionite under N2 gave an electrochemical potential (E' 0) of -276 mV relative to the normal hydrogen electrode. Electrochemical titration of the cytochrome gave a Nernst plot with two linear regions with E' 0 values of -0.376 and -0.534 V. The spectra produced at various potentials exhibited shifts in isosbestic points upon reduction, suggesting changes in conformation during the reaction."}
{"id": "PMID:230180", "title": "Biosynthesis of phospholipids in Bacillus megaterium.", "content": "Information on the biosynthesis of phospholipids in bacteria has been derived principally from the study of Escherichia coli and other gram-negative organisms. We have now carried out a detailed study of the pathways of phospholipid biosynthesis in the gram-positive organism Bacillus megarterium KM in relation to investigations on the biogenesis of lipid asymmetry in membranes. Radioactive precursors such as 32Pi and [3H]palmitate initially label phosphatidylethanolamine much more than phosphatidylglycerol. This raised the possibility that phosphatidylglycerol may be the precursor of phosphatidylethanolamine in a pathway different from that in E. coli. Phosphatidylglycerol is known to be highly reactive metabolically, since it functions as a donor of phosphatidyl residues in the synthesis of cardiolipin and as  a donor of glycerophosphate residues in the synthesis of teichoic acids and of membrane-derived oligosaccharides. The large pool of phosphatidylglycerol would dilute the radioactive isotope, slowing the initial rate of incorporation of label into phosphatidylethanolamine. However, assays of cell-free extracts revealed no evidence for such a novel pathway. Instead, phosphatidylserine synthase (cytidine 5'-diphosphate-diglyceride:L-serine phosphatidyl transferase) and phosphatidylserine decarboxylase were detected, although at low levels. These results suggest that the pathway in B. megaterium is the same as that in E. coli in which phosphatidylserine, derived from cytidine 5'-diphosphate-diglyceride, is the precursor of phosphatidylethanolamine. The lag in the appearance of label in phosphatidylethanolamine appears to be the effect of a considerable pool of phosphatidylserine (ca. 5 to 10% of the total phospholipid) in certain strains of B. megaterium. The lag in labeling can be correlated with the size of the pool of phosphatidylserine. Pulse-chase experiments in vivo support the conclusion that in B. megaterium phosphatidylserine is not derived from phosphatidylglycerol. Rates of turnover of the membrane phospholipids of B. megaterium have also been studied.", "contents": "Biosynthesis of phospholipids in Bacillus megaterium. Information on the biosynthesis of phospholipids in bacteria has been derived principally from the study of Escherichia coli and other gram-negative organisms. We have now carried out a detailed study of the pathways of phospholipid biosynthesis in the gram-positive organism Bacillus megarterium KM in relation to investigations on the biogenesis of lipid asymmetry in membranes. Radioactive precursors such as 32Pi and [3H]palmitate initially label phosphatidylethanolamine much more than phosphatidylglycerol. This raised the possibility that phosphatidylglycerol may be the precursor of phosphatidylethanolamine in a pathway different from that in E. coli. Phosphatidylglycerol is known to be highly reactive metabolically, since it functions as a donor of phosphatidyl residues in the synthesis of cardiolipin and as  a donor of glycerophosphate residues in the synthesis of teichoic acids and of membrane-derived oligosaccharides. The large pool of phosphatidylglycerol would dilute the radioactive isotope, slowing the initial rate of incorporation of label into phosphatidylethanolamine. However, assays of cell-free extracts revealed no evidence for such a novel pathway. Instead, phosphatidylserine synthase (cytidine 5'-diphosphate-diglyceride:L-serine phosphatidyl transferase) and phosphatidylserine decarboxylase were detected, although at low levels. These results suggest that the pathway in B. megaterium is the same as that in E. coli in which phosphatidylserine, derived from cytidine 5'-diphosphate-diglyceride, is the precursor of phosphatidylethanolamine. The lag in the appearance of label in phosphatidylethanolamine appears to be the effect of a considerable pool of phosphatidylserine (ca. 5 to 10% of the total phospholipid) in certain strains of B. megaterium. The lag in labeling can be correlated with the size of the pool of phosphatidylserine. Pulse-chase experiments in vivo support the conclusion that in B. megaterium phosphatidylserine is not derived from phosphatidylglycerol. Rates of turnover of the membrane phospholipids of B. megaterium have also been studied."}
{"id": "PMID:230181", "title": "Studies on the allosteric nature of acetate kinase from Bacillus stearothermophilus.", "content": "Fructose 1,6-bisphosphate (FBP) stimulates the reaction of Bacillus stearothermophilus acetate kinase (AK). FBP changes the reaction curve for ATP from a sigmoidal type to a Michaelis-Menten one. The binding of FBP to AK was studied by an equilibrium dialysis method and by measuring changes in fluorescence. The extent of binding of FBP to the enzyme paralleled its activation. In addition, the binding constant for FBP increased in the presence of substrate, ATP. These results suggest that FBP is an allosteric activator of B. stearothermophilus AK. Only two moles of FBP bound to this tetrameric enzyme. No cooperativity was found for the binding of FBP. These observations support the previous conclusion, that a set of two subunits in the tetramer is a unit of the enzymatic function. A model is presented to interpret the sigmoidal kinetics for ATP, the absence of cooperativity for FBP binding, and the allosteric activation by FBP of this enzyme. The kinetic properties of the enzyme can be explained quantitatively by this model.", "contents": "Studies on the allosteric nature of acetate kinase from Bacillus stearothermophilus. Fructose 1,6-bisphosphate (FBP) stimulates the reaction of Bacillus stearothermophilus acetate kinase (AK). FBP changes the reaction curve for ATP from a sigmoidal type to a Michaelis-Menten one. The binding of FBP to AK was studied by an equilibrium dialysis method and by measuring changes in fluorescence. The extent of binding of FBP to the enzyme paralleled its activation. In addition, the binding constant for FBP increased in the presence of substrate, ATP. These results suggest that FBP is an allosteric activator of B. stearothermophilus AK. Only two moles of FBP bound to this tetrameric enzyme. No cooperativity was found for the binding of FBP. These observations support the previous conclusion, that a set of two subunits in the tetramer is a unit of the enzymatic function. A model is presented to interpret the sigmoidal kinetics for ATP, the absence of cooperativity for FBP binding, and the allosteric activation by FBP of this enzyme. The kinetic properties of the enzyme can be explained quantitatively by this model."}
{"id": "PMID:230183", "title": "Mitochondrial and cytosolic localization of a single glycerate kinase in rat kidney cortex.", "content": "The distribution of glycerate kinase [ATP:D-glycerate 2-phosphotransferase, EC 2.7.1.31] in kidney was studied. This enzyme was found to be present in the renal cortex. By differential centrifugation of the homogenate and sucrose density gradient analysis, it was found that 42% and 60% of the renal glycerate kinase were localized in the cytosol and mitochondria, respectively. The mitochondrial enzyme appeared to be present in the inner membrane and/or matrix. No difference was found between the solubilized-mitochondrial and cytosolic glycerate kinase as regards kinetic properties, thermal stability, electrochemical properties, and molecular size. Immunochemical identity of these enzymes was demonstrated using a rabbit antibody against mitochondrial glycerate kinase purified from rat liver. Although the hepatic enzyme was induced by dietary protein (Kitagawa, Y., Katayama, H., & Sugimoto, E. [1979] Biochim. Biophys. Acta 582, 260--275), the renal enzyme in mitochondria and cytosol was not affected by dietary protein. These results on renal glycerate kinase are compared with those for the hepatic enzyme, and the regulatory mechanism for intracellular distribution of the enzymes is discussed.", "contents": "Mitochondrial and cytosolic localization of a single glycerate kinase in rat kidney cortex. The distribution of glycerate kinase [ATP:D-glycerate 2-phosphotransferase, EC 2.7.1.31] in kidney was studied. This enzyme was found to be present in the renal cortex. By differential centrifugation of the homogenate and sucrose density gradient analysis, it was found that 42% and 60% of the renal glycerate kinase were localized in the cytosol and mitochondria, respectively. The mitochondrial enzyme appeared to be present in the inner membrane and/or matrix. No difference was found between the solubilized-mitochondrial and cytosolic glycerate kinase as regards kinetic properties, thermal stability, electrochemical properties, and molecular size. Immunochemical identity of these enzymes was demonstrated using a rabbit antibody against mitochondrial glycerate kinase purified from rat liver. Although the hepatic enzyme was induced by dietary protein (Kitagawa, Y., Katayama, H., & Sugimoto, E. [1979] Biochim. Biophys. Acta 582, 260--275), the renal enzyme in mitochondria and cytosol was not affected by dietary protein. These results on renal glycerate kinase are compared with those for the hepatic enzyme, and the regulatory mechanism for intracellular distribution of the enzymes is discussed."}
{"id": "PMID:230185", "title": "Organ secificity of rat sodium- and potassium-activated adenosine triphosphatase.", "content": "We compared several Na,K-ATPase preparations from various organs of the rat. The brain Na,K-ATPase differed from the enzymes of other organs in its pH dependence and responses to ouabain and N-ethylmaleimide in spite of similarities in the kinetic parameters of activation by Na+, K+, Mg2+, and ATP. The optimum pH of the brain MaI-enzyme was at 7.4 to 7.5 at 37 degrees D. The Lubrol extract of this brain enzyme preparation showed a lower optimum oH of 6.6. When the Lubrol extract of the brain was fractionated wtih (NH4)2SO4, the activity of the precipitate in the neutral pH region was restored. On the other hand, the optimum pH of the kidney NaI-enzyme was slightly affected by Lubrol and ammonium sulfate treatments (pH 7.5 leads to 7.3). The brain enzyme (K 1/2 = 0.9 microM) showed about 100-fold higher sensitivity to ouabain than the enzymes from other organs (I 1/2 = 100 microM) in the presence of 120 mM Na+ and 10 mM K+. In a Hill plot of the ouabain inhibition, the former failed to give a linear relationship, while the latter gave a straight line with a Hill coefficient of 1.0. The effect of K4 on the brain enzyme-ouabain interaction led us to consider that the brain enzyme might have two components as regards ouabain affinity, high and low affinity components. The time course of N-ethylmaleimide inhibition of the brain enzyme was rapid and biphasic, while the kidney enzyme showed only a slow phase following pseudo-first order kinetics. ATP protected the kidney enzyme activity completely agai,st N-ethylmaleimide inhibition, but the protection of the brain enzyme activity by ATP was only partial. We divided rat Na,K-ATPases into two groups, the brain type, which is restricted to the central nervous system, and the kidney type, which is found in most organs.", "contents": "Organ secificity of rat sodium- and potassium-activated adenosine triphosphatase. We compared several Na,K-ATPase preparations from various organs of the rat. The brain Na,K-ATPase differed from the enzymes of other organs in its pH dependence and responses to ouabain and N-ethylmaleimide in spite of similarities in the kinetic parameters of activation by Na+, K+, Mg2+, and ATP. The optimum pH of the brain MaI-enzyme was at 7.4 to 7.5 at 37 degrees D. The Lubrol extract of this brain enzyme preparation showed a lower optimum oH of 6.6. When the Lubrol extract of the brain was fractionated wtih (NH4)2SO4, the activity of the precipitate in the neutral pH region was restored. On the other hand, the optimum pH of the kidney NaI-enzyme was slightly affected by Lubrol and ammonium sulfate treatments (pH 7.5 leads to 7.3). The brain enzyme (K 1/2 = 0.9 microM) showed about 100-fold higher sensitivity to ouabain than the enzymes from other organs (I 1/2 = 100 microM) in the presence of 120 mM Na+ and 10 mM K+. In a Hill plot of the ouabain inhibition, the former failed to give a linear relationship, while the latter gave a straight line with a Hill coefficient of 1.0. The effect of K4 on the brain enzyme-ouabain interaction led us to consider that the brain enzyme might have two components as regards ouabain affinity, high and low affinity components. The time course of N-ethylmaleimide inhibition of the brain enzyme was rapid and biphasic, while the kidney enzyme showed only a slow phase following pseudo-first order kinetics. ATP protected the kidney enzyme activity completely agai,st N-ethylmaleimide inhibition, but the protection of the brain enzyme activity by ATP was only partial. We divided rat Na,K-ATPases into two groups, the brain type, which is restricted to the central nervous system, and the kidney type, which is found in most organs."}
{"id": "PMID:230186", "title": "Effects of temperature on cytochrome oxidase activity in solubilized form and in lipid vesicle systems.", "content": "Isolated mammalian cytochrome oxidase gave an Arrhenius plot with a break (Tb) at about 20 degrees C when assayed in a medium containing Emasol. The activation energies above and below 20 degrees C were 9.3 (EH) and 18.9 kcal/mol (EL), respectively. Isolated cytochrome oxidase was also incorporated into vesicles of dipalmitoyl phosphatidylcholine (DPPC, phase transition temperature Tt = 40 degrees C), dimyristoyl phosphatidylcholine (DMPC, Tt = 23 degrees C) and dioleoyl phosphatidylcholine (DOPC, Tt = -22 degrees C). The DPPC system showed a nearly linear Arrhenius plot between 9 and 36 degrees C with E = 22.8 kcal/mol. When cytochrome oxidase was resolubilized from the DPPC vesicles and assayed in solution a biphasic plot was obtained again. Cytochrome oxidase-DOPC was more active than the solubilized enzyme and exhibited a biphasic Arrhenius plot with Tb = 23 degrees C. EH and EL were 6.6 and 15.8 kcal/mol, respectively. The plot for the oxidase-DMPC also showed a break (Tb = 26 degrees C) with EH = 6.6 and EL = 26.6 kcal/mol. These results indicate that the break in the Arrhenius plot reflects primarily a structural transition in the cytochrome oxidase molecule between the \"hot\" and \"cold\" conformations, as proposed previously. This transition, as well as the molecular state of cytochrome oxidase, is affected by the physical state of the membrane lipids as reflected by changes in the kinetic properties.", "contents": "Effects of temperature on cytochrome oxidase activity in solubilized form and in lipid vesicle systems. Isolated mammalian cytochrome oxidase gave an Arrhenius plot with a break (Tb) at about 20 degrees C when assayed in a medium containing Emasol. The activation energies above and below 20 degrees C were 9.3 (EH) and 18.9 kcal/mol (EL), respectively. Isolated cytochrome oxidase was also incorporated into vesicles of dipalmitoyl phosphatidylcholine (DPPC, phase transition temperature Tt = 40 degrees C), dimyristoyl phosphatidylcholine (DMPC, Tt = 23 degrees C) and dioleoyl phosphatidylcholine (DOPC, Tt = -22 degrees C). The DPPC system showed a nearly linear Arrhenius plot between 9 and 36 degrees C with E = 22.8 kcal/mol. When cytochrome oxidase was resolubilized from the DPPC vesicles and assayed in solution a biphasic plot was obtained again. Cytochrome oxidase-DOPC was more active than the solubilized enzyme and exhibited a biphasic Arrhenius plot with Tb = 23 degrees C. EH and EL were 6.6 and 15.8 kcal/mol, respectively. The plot for the oxidase-DMPC also showed a break (Tb = 26 degrees C) with EH = 6.6 and EL = 26.6 kcal/mol. These results indicate that the break in the Arrhenius plot reflects primarily a structural transition in the cytochrome oxidase molecule between the \"hot\" and \"cold\" conformations, as proposed previously. This transition, as well as the molecular state of cytochrome oxidase, is affected by the physical state of the membrane lipids as reflected by changes in the kinetic properties."}
{"id": "PMID:230187", "title": "Thymidine kinase enzyme variants in Physarum polycephalum. In vitro interconversion of the enzyme variants.", "content": "Isoelectric focusing of plasmodial extracts of Physarum polycephalum demonstrated the presence of several multiple enzyme variants of thymidine kinase, which appear sequentially during the nuclear division cycle. Variants (A) + (A1) are the only enzyme variants found in the late G2-phase, whereas the variants (C) + (C1) are only present at the time of mitosis and S-phase (1, 2). Evidence is presented that multiple forms of thymidine kinase (A) + (A1) with high pI arise by dephosphorylation of a primary translation product with low pI (C and/or C1). The thymidine kinase fractions (A) + (A1) and (C) + (C1) + (c1) were separated and partially purified by DEAE-cellulose chromatography. The enzyme variants (C) + (C1) are converted in vitro by an endogenous enzymatic factor as well as by bacterial alkaline phosphatase into the variants (A) + (A1).", "contents": "Thymidine kinase enzyme variants in Physarum polycephalum. In vitro interconversion of the enzyme variants. Isoelectric focusing of plasmodial extracts of Physarum polycephalum demonstrated the presence of several multiple enzyme variants of thymidine kinase, which appear sequentially during the nuclear division cycle. Variants (A) + (A1) are the only enzyme variants found in the late G2-phase, whereas the variants (C) + (C1) are only present at the time of mitosis and S-phase (1, 2). Evidence is presented that multiple forms of thymidine kinase (A) + (A1) with high pI arise by dephosphorylation of a primary translation product with low pI (C and/or C1). The thymidine kinase fractions (A) + (A1) and (C) + (C1) + (c1) were separated and partially purified by DEAE-cellulose chromatography. The enzyme variants (C) + (C1) are converted in vitro by an endogenous enzymatic factor as well as by bacterial alkaline phosphatase into the variants (A) + (A1)."}
{"id": "PMID:230188", "title": "Multilayer planar membranes of sarcoplasmic reticulum.", "content": "Multilayer planar membranes were constructed between a pair of cellulose sheets from fragmented sarcoplasmic reticulum (FSR) as well as a mixture of egg yolk lecithin and the Ca2+-ATPase purified from FSR. Since sodium deoxycholate was used instead of organic solvents in order to dissolve phospholipids in the process of the membrane preparation, the total activity of the Ca2+-ATPase was still preserved in the planar membrane of FSR. It was also indicated using a spin label technique that the orientation of phospholipids in the planar membrane of FSR was considerably disturbed by the presence of proteins such as the Ca2+-ATPase included in FSR.", "contents": "Multilayer planar membranes of sarcoplasmic reticulum. Multilayer planar membranes were constructed between a pair of cellulose sheets from fragmented sarcoplasmic reticulum (FSR) as well as a mixture of egg yolk lecithin and the Ca2+-ATPase purified from FSR. Since sodium deoxycholate was used instead of organic solvents in order to dissolve phospholipids in the process of the membrane preparation, the total activity of the Ca2+-ATPase was still preserved in the planar membrane of FSR. It was also indicated using a spin label technique that the orientation of phospholipids in the planar membrane of FSR was considerably disturbed by the presence of proteins such as the Ca2+-ATPase included in FSR."}
{"id": "PMID:230189", "title": "Trophoblastic tumors in Greenland.", "content": "From 1950 through 1974, 37 cases of hydatidiform mole not followed by malignancy and 11 cases of invasively growing trophoblastic tumors (IGTT) occurred among indigenous Greenlandic women. The overall incidence of benign mole was 1:850 births, only slightly higher than most incidences in low-risk areas like Western Europe, North America, Australia, and Israel. In contrast, the overall incidence of IGTT, 1:2861 births, and the minimum incidence of histologically confirmed choriocarcinoma, 1:5245 births, are among the highest population-based incidence on record. A marked increase in incidence of both hydatidiform mole and IGTT was found late in reproductive life. A recent high incidence of mole among teenagers increased the incidence with statistical significance during the latest 10 years, whereas maximum incidence of IGTT was found in 1960--64. A strong association existed between hydatidiform mole and IGTT. During the study period Greenlandic women with mole had a 20% risk of developing IGTT and 64% of IGTT cases were preceded by molar pregnancy. Four cases of benign mole, but no case of IGTT, occurred among the small group of Danish women living in Greeland. The incidence, 1 mole:685 births, was higher than among the indigenous population, although the latter had a lower socio-economic status. The reason for the high occurrence of IGTT among indigenous Greenlanders remains unknown. The predominating HL-A 9 antigen could conceivably reflect a genetic predisposition.", "contents": "Trophoblastic tumors in Greenland. From 1950 through 1974, 37 cases of hydatidiform mole not followed by malignancy and 11 cases of invasively growing trophoblastic tumors (IGTT) occurred among indigenous Greenlandic women. The overall incidence of benign mole was 1:850 births, only slightly higher than most incidences in low-risk areas like Western Europe, North America, Australia, and Israel. In contrast, the overall incidence of IGTT, 1:2861 births, and the minimum incidence of histologically confirmed choriocarcinoma, 1:5245 births, are among the highest population-based incidence on record. A marked increase in incidence of both hydatidiform mole and IGTT was found late in reproductive life. A recent high incidence of mole among teenagers increased the incidence with statistical significance during the latest 10 years, whereas maximum incidence of IGTT was found in 1960--64. A strong association existed between hydatidiform mole and IGTT. During the study period Greenlandic women with mole had a 20% risk of developing IGTT and 64% of IGTT cases were preceded by molar pregnancy. Four cases of benign mole, but no case of IGTT, occurred among the small group of Danish women living in Greeland. The incidence, 1 mole:685 births, was higher than among the indigenous population, although the latter had a lower socio-economic status. The reason for the high occurrence of IGTT among indigenous Greenlanders remains unknown. The predominating HL-A 9 antigen could conceivably reflect a genetic predisposition."}
{"id": "PMID:230190", "title": "Secretion and degradation of parathormone as a function of intracellular maturation of hormone pools. Modulation by calcium and dibutyryl cyclic AMP.", "content": "The biosynthesis, processing, and secretion of parthormone and the effect of calcium on these processes were measured in dispersed porcine parthyroid cells incubated with [(35)S]methionine. Proparathormone was detected at 10 min, the earliest time measured, and was rapidly and apparently quantitatively converted to parathormone. The half-life of the prohomormone pool was 15 min. Secretion of parathormone was detected by 20 min. In pulse-chase experiments there was a period between 20 and 40 min during which the wave of newly-synthesized parathormone was secreted. After 40 min during little additional radioactive hormone was secreted, but dibutyryl cyclic AMP, an agent that can mobilize stored parathormone, when added to the incubation mixtures enhanced radioactive parathormone secretion but only after 60 min, although it increased net hormone secretion as determined by radioimmunoassay to the same extent at all times studied. When the ionized calcium concentration of the medium was lowered, more radioactive hormone was secreted at all times but the effect was greatest on that hormone that was synthesized less than 60 min previously ; however, net hormone secretion in contrast to radioactive hormone was enhanced equally at all intervals. These data could mean that the refractoriness to secretion of parathormone 40-60 min of age was related to maturation of secretory container preparatory to storage. Low calcium (0.5 mM) stimulated hormone secretion up to fivefold compared to high calcium (3.0 mM) but did not affect synthesis of parathormone or proparathormne or conversion of the latter to hormone. During processing at least 70 percent of the intracellular parathormone was lost, presumably through proteolysis and this degradation was greater at high calcium. These data have been interpreted in light of the concept that two secretable pools of parathormone exist within the parathyroid.", "contents": "Secretion and degradation of parathormone as a function of intracellular maturation of hormone pools. Modulation by calcium and dibutyryl cyclic AMP. The biosynthesis, processing, and secretion of parthormone and the effect of calcium on these processes were measured in dispersed porcine parthyroid cells incubated with [(35)S]methionine. Proparathormone was detected at 10 min, the earliest time measured, and was rapidly and apparently quantitatively converted to parathormone. The half-life of the prohomormone pool was 15 min. Secretion of parathormone was detected by 20 min. In pulse-chase experiments there was a period between 20 and 40 min during which the wave of newly-synthesized parathormone was secreted. After 40 min during little additional radioactive hormone was secreted, but dibutyryl cyclic AMP, an agent that can mobilize stored parathormone, when added to the incubation mixtures enhanced radioactive parathormone secretion but only after 60 min, although it increased net hormone secretion as determined by radioimmunoassay to the same extent at all times studied. When the ionized calcium concentration of the medium was lowered, more radioactive hormone was secreted at all times but the effect was greatest on that hormone that was synthesized less than 60 min previously ; however, net hormone secretion in contrast to radioactive hormone was enhanced equally at all intervals. These data could mean that the refractoriness to secretion of parathormone 40-60 min of age was related to maturation of secretory container preparatory to storage. Low calcium (0.5 mM) stimulated hormone secretion up to fivefold compared to high calcium (3.0 mM) but did not affect synthesis of parathormone or proparathormne or conversion of the latter to hormone. During processing at least 70 percent of the intracellular parathormone was lost, presumably through proteolysis and this degradation was greater at high calcium. These data have been interpreted in light of the concept that two secretable pools of parathormone exist within the parathyroid."}
{"id": "PMID:230191", "title": "Effects of cytoskeletal perturbant drugs on ecto 5'-nucleotidase, a concanavalin A receptor.", "content": "Differences in cell morphology, concanavalin A-induced receptor redistributions, and the cooperativity of the inhibition of 5'-nucleotidase (AMPase) by concanavalin A (Con A) have been investigated in ascites sublines of the 13762 rat mammary adenocarcinoma cells treated with microfilament- and microtubule-perturbing drugs. By scanning electron microscopy MAT-C1 cells exhibit a highly irregular surface, covered with microvilli extending as branched structures from the cell body. MAT-A, MAT-B, and MAT-B1 cells have a more normal appearance, with unbranched microvilli, ruffles, ridges, and blebs associated closely with the cell body. MAT-C cells have an intermediate morphology. Treatment of MAT-A, MAT-B, or MAT-B1 cells with Con A causes rapid redistribution of Con A receptors. Both cytochalasins and colchicine cause alternations in the receptor redistributions. Receptors on MAT-C1 cells are highly resistant to redistribution, even in the presence of cytoskeletal perturbant drugs. The cooperativity of the inhibition of AMPase by Con A was investigated in MAT-A and MAT-C1 cells. Untreated cells exhibit no cooperativity. If either subline is treated with colchicine, cytochalasin B or D, or dibucaine, cooperativity is observed. Lumicolchicine has no effect. Theophylline or dibutyryl cyclic AMP prevents the effects of either colchicine or cytochalasin. The concentration required for half-maximal induction of cooperativity is 0.3--0.4 microM for both colchicine and cytochalasin D, which is in the appropriate range for specific microtubule and microfilament disruptions. The effectiveness of the cytochalasins (E greater than D greater than B) is consistent with their known effects on microfilaments. No direct correlation was observed between the induction of cooperativity and drug-induced changes in Con A receptor redistribution or cell morphology. The morphology of MAT-A cells is grossly altered by cytochalasins or dibucaine and somewhat less by colchicine. MAT-C1 cells exhibit more minor alterations in morphology as a result of these drug treatments. The results of this study indicate that the inhibition of AMPase, which is a Con A receptor, is a different process from the redistribution of the bulk of the Con A receptors, possibly short range membrane interactions rather than global effects on the cell.", "contents": "Effects of cytoskeletal perturbant drugs on ecto 5'-nucleotidase, a concanavalin A receptor. Differences in cell morphology, concanavalin A-induced receptor redistributions, and the cooperativity of the inhibition of 5'-nucleotidase (AMPase) by concanavalin A (Con A) have been investigated in ascites sublines of the 13762 rat mammary adenocarcinoma cells treated with microfilament- and microtubule-perturbing drugs. By scanning electron microscopy MAT-C1 cells exhibit a highly irregular surface, covered with microvilli extending as branched structures from the cell body. MAT-A, MAT-B, and MAT-B1 cells have a more normal appearance, with unbranched microvilli, ruffles, ridges, and blebs associated closely with the cell body. MAT-C cells have an intermediate morphology. Treatment of MAT-A, MAT-B, or MAT-B1 cells with Con A causes rapid redistribution of Con A receptors. Both cytochalasins and colchicine cause alternations in the receptor redistributions. Receptors on MAT-C1 cells are highly resistant to redistribution, even in the presence of cytoskeletal perturbant drugs. The cooperativity of the inhibition of AMPase by Con A was investigated in MAT-A and MAT-C1 cells. Untreated cells exhibit no cooperativity. If either subline is treated with colchicine, cytochalasin B or D, or dibucaine, cooperativity is observed. Lumicolchicine has no effect. Theophylline or dibutyryl cyclic AMP prevents the effects of either colchicine or cytochalasin. The concentration required for half-maximal induction of cooperativity is 0.3--0.4 microM for both colchicine and cytochalasin D, which is in the appropriate range for specific microtubule and microfilament disruptions. The effectiveness of the cytochalasins (E greater than D greater than B) is consistent with their known effects on microfilaments. No direct correlation was observed between the induction of cooperativity and drug-induced changes in Con A receptor redistribution or cell morphology. The morphology of MAT-A cells is grossly altered by cytochalasins or dibucaine and somewhat less by colchicine. MAT-C1 cells exhibit more minor alterations in morphology as a result of these drug treatments. The results of this study indicate that the inhibition of AMPase, which is a Con A receptor, is a different process from the redistribution of the bulk of the Con A receptors, possibly short range membrane interactions rather than global effects on the cell."}
{"id": "PMID:230192", "title": "Effect of cell density on binding and uptake of low density lipoprotein by human fibroblasts.", "content": "The effect of cell density on low density lipoprotein (LDL) binding by cultured human skin fibroblasts was investigated. Bound LDL was visualized by indirect immunofluorescence. Cellular lipid and cholesterol were monitored by fluorescence in cells stained with phosphine 3R and filipin, respectively. LDL binding and lipid accumulation were compared in cells in stationary and exponentially growing cultures, in sparsely and densely plated cultures, in wounded and non-wounded areas of stationary cultures, and in stationary cultures with and without the addition of lipoprotein-deficient serum. We conclude that LDL binding and cholesterol accumulation induced by LDL are influenced by cell density. It appears that, compared to rapidly growing cells, quiescent (noncycling) human fibroblasts exhibit fewer functional LDL receptors.", "contents": "Effect of cell density on binding and uptake of low density lipoprotein by human fibroblasts. The effect of cell density on low density lipoprotein (LDL) binding by cultured human skin fibroblasts was investigated. Bound LDL was visualized by indirect immunofluorescence. Cellular lipid and cholesterol were monitored by fluorescence in cells stained with phosphine 3R and filipin, respectively. LDL binding and lipid accumulation were compared in cells in stationary and exponentially growing cultures, in sparsely and densely plated cultures, in wounded and non-wounded areas of stationary cultures, and in stationary cultures with and without the addition of lipoprotein-deficient serum. We conclude that LDL binding and cholesterol accumulation induced by LDL are influenced by cell density. It appears that, compared to rapidly growing cells, quiescent (noncycling) human fibroblasts exhibit fewer functional LDL receptors."}
{"id": "PMID:230193", "title": "A crystalline inclusion in sieve element nuclei of Amsinckia. I. The inclusion in differentiating cells.", "content": "The presence of usually single, elongated, compound crystalloids in nuclei of sieve elements is an outstanding characteristic of the phloem of Amsinckia douglasiana A. DC. (Boraginaceae). The crystalloid consists of two components forming alternating panels, or blocks, that extend through the entire length of the crystalloid and radiate from the centre where one of the components predominates. Three to seven panels for each component were recorded. One component consists of 4-sided tubules closely packed in highly ordered aggregates, the other of wider 6-sided tubules rather loosely arranged in paracrystalline aggregates. The crystalloid arises at the beginning of sieve element differentiation. Aggregates of 4-sided tubules appear first. In plants infected with the curly top virus, the crystalloids do not differ from those in non-infected controls in structure and conformation. But because the phloem in infected plants is hyperplastic, with most of the cells differentiating as sieve elements, the crystalloids are far more abundant in diseased than in healthy plants.", "contents": "A crystalline inclusion in sieve element nuclei of Amsinckia. I. The inclusion in differentiating cells. The presence of usually single, elongated, compound crystalloids in nuclei of sieve elements is an outstanding characteristic of the phloem of Amsinckia douglasiana A. DC. (Boraginaceae). The crystalloid consists of two components forming alternating panels, or blocks, that extend through the entire length of the crystalloid and radiate from the centre where one of the components predominates. Three to seven panels for each component were recorded. One component consists of 4-sided tubules closely packed in highly ordered aggregates, the other of wider 6-sided tubules rather loosely arranged in paracrystalline aggregates. The crystalloid arises at the beginning of sieve element differentiation. Aggregates of 4-sided tubules appear first. In plants infected with the curly top virus, the crystalloids do not differ from those in non-infected controls in structure and conformation. But because the phloem in infected plants is hyperplastic, with most of the cells differentiating as sieve elements, the crystalloids are far more abundant in diseased than in healthy plants."}
{"id": "PMID:230194", "title": "A crystalline inclusion in sieve element nuclei of Amsinckia. II. The inclusion in maturing cells.", "content": "The compounds crystalloids formed in sieve element nuclei of Amsinckia douglasiana A. DC. (Boraginaceae) during differentiation of the cell become disaggregated during the nuclear breakdown characteristic of a maturing sieve element. The phenomenon occurs in both healthy and virus-infected plants. The crystalloid component termed cy, which is loosely aggregated, separates from the densely aggregated component termed cx and disperses. The cx component may become fragmented, or broken into large pieces, or remain intact after the cell matures. After their release from the nucleus both crystalloid components become spatially associated with the dispersed P-protein originating in the cytoplasm, but remain distinguishable from it. The component tubules of P-protein are hexagonal in transections and are somewhat wider than the 6-sided cy tubules. The cx tubules are much narrower than the P-protein or the cy tubules and have square transections. Both the P-protein and the products of disintegrated crystalloids accumulate at sieve plates in sieve elements subjected to sudden release of hydrostatic pressure by cutting the phloem. The question of categorizing the tubular components of the nuclear crystalloid of a sieve element with reference to the concept of P-protein is discussed.", "contents": "A crystalline inclusion in sieve element nuclei of Amsinckia. II. The inclusion in maturing cells. The compounds crystalloids formed in sieve element nuclei of Amsinckia douglasiana A. DC. (Boraginaceae) during differentiation of the cell become disaggregated during the nuclear breakdown characteristic of a maturing sieve element. The phenomenon occurs in both healthy and virus-infected plants. The crystalloid component termed cy, which is loosely aggregated, separates from the densely aggregated component termed cx and disperses. The cx component may become fragmented, or broken into large pieces, or remain intact after the cell matures. After their release from the nucleus both crystalloid components become spatially associated with the dispersed P-protein originating in the cytoplasm, but remain distinguishable from it. The component tubules of P-protein are hexagonal in transections and are somewhat wider than the 6-sided cy tubules. The cx tubules are much narrower than the P-protein or the cy tubules and have square transections. Both the P-protein and the products of disintegrated crystalloids accumulate at sieve plates in sieve elements subjected to sudden release of hydrostatic pressure by cutting the phloem. The question of categorizing the tubular components of the nuclear crystalloid of a sieve element with reference to the concept of P-protein is discussed."}
{"id": "PMID:230195", "title": "Cytology, growth characteristics and cellular alterations following SV40-induced transformation of human foetal brain cells derived from a Gm2 gangliosidosis and control.", "content": "Cell cultures were derived from the cerebra of a control and a Gm2 gangliosidosis (Tay-Sachs disease (TSD)) foetus. Both cell lines were identified as astrocytic, based on the ultrastructural demonstration of glial fibres. The control culture exhibited morphological differentiation when exposed to dibutyryl cAMP, a finding which was not observed with the TSD cells. The TSD culture demonstrated the pathobiological features of the disease, which included the absence of hexosaminidase A, increased concentration of Gm2 ganglioside and the detection of membranous cytoplasmic bodies by electron microscopy. Control and TSD cells were exposed to SV40 virus, resulting ultimately in the isolation of transformants which differed from the parental cell types in morphology, growth rate and greatly accelerated cell death. Both control and TSD cell lines have been in propagation for over 200 subcultures and the transformants were identified as astrocytic, based on the retention of characteristic glial fibres. The control culture demonstrated a chromosome range of 34--63, with a mean of 47. In contrast, the TSD transformants exhibited a range of 50--107 and a mean of 74. Transformed lines retained their parental hexosaminidase isoenzyme profiles; Hex A and B in control, and Hex B in TSD cells. Membraneous cytoplasmic bodies persisted in the TSD line. Neither line could be induced to differentiate after exposure to cAMP. Additionally, they had a population doubling time of under 85 h and failed to release infectious virus particles. Significant alterations in the total quantity and distribution profile of gangliosides were noted following viral transformation. A large increase in the percentage of Gm3 and a more modest increase in Gm2 were detected. In contrast, transformed lines were characterized by substantial reduction in the percentage of glucosamine-containing Gm2 and polysialoganglioside. Additionally, cultures exhibited a characteristic reduction in ganglioside content after transformation. The in vitro transformation of human brain cells has resulted in the derivation of permanent astrocytic lines which are, by virtue of their rapid growth rate and long-term survival, uniquely suited and adapted to the large scale in vitro production of substantial quantities of cells required for extensive biochemical study. Significantly, those characteristics which are unique to the Gm2 gangliosidosis storage disease have been retained in a permanent model CNS cell line.", "contents": "Cytology, growth characteristics and cellular alterations following SV40-induced transformation of human foetal brain cells derived from a Gm2 gangliosidosis and control. Cell cultures were derived from the cerebra of a control and a Gm2 gangliosidosis (Tay-Sachs disease (TSD)) foetus. Both cell lines were identified as astrocytic, based on the ultrastructural demonstration of glial fibres. The control culture exhibited morphological differentiation when exposed to dibutyryl cAMP, a finding which was not observed with the TSD cells. The TSD culture demonstrated the pathobiological features of the disease, which included the absence of hexosaminidase A, increased concentration of Gm2 ganglioside and the detection of membranous cytoplasmic bodies by electron microscopy. Control and TSD cells were exposed to SV40 virus, resulting ultimately in the isolation of transformants which differed from the parental cell types in morphology, growth rate and greatly accelerated cell death. Both control and TSD cell lines have been in propagation for over 200 subcultures and the transformants were identified as astrocytic, based on the retention of characteristic glial fibres. The control culture demonstrated a chromosome range of 34--63, with a mean of 47. In contrast, the TSD transformants exhibited a range of 50--107 and a mean of 74. Transformed lines retained their parental hexosaminidase isoenzyme profiles; Hex A and B in control, and Hex B in TSD cells. Membraneous cytoplasmic bodies persisted in the TSD line. Neither line could be induced to differentiate after exposure to cAMP. Additionally, they had a population doubling time of under 85 h and failed to release infectious virus particles. Significant alterations in the total quantity and distribution profile of gangliosides were noted following viral transformation. A large increase in the percentage of Gm3 and a more modest increase in Gm2 were detected. In contrast, transformed lines were characterized by substantial reduction in the percentage of glucosamine-containing Gm2 and polysialoganglioside. Additionally, cultures exhibited a characteristic reduction in ganglioside content after transformation. The in vitro transformation of human brain cells has resulted in the derivation of permanent astrocytic lines which are, by virtue of their rapid growth rate and long-term survival, uniquely suited and adapted to the large scale in vitro production of substantial quantities of cells required for extensive biochemical study. Significantly, those characteristics which are unique to the Gm2 gangliosidosis storage disease have been retained in a permanent model CNS cell line."}
{"id": "PMID:230196", "title": "Granulocyte adhesion to endothelium in culture.", "content": "We previously described a model system for studying the adherence of granulocytes to cultured endothelium, and have now investigated the effects of other blood components on granulocyte adhesion in this system. Red cells enhanced adhesion, whereas blood platelets decreased adhesion, and further experiments suggested that endothelial cells secrete a proadhesive factor, particularly if incubated with plasma. We have also investigated the effects of several drugs, and attempted to localize their sites of action. Flavonoid drugs increased adhesion by an effect at the endothelial cell surface, whereas agents that increase cyclic AMP levels, including several prostaglandins, stimulated adhesion mainly by their effects on granulocytes. The effects of some agents on granulocyte adhesion to endothelium were not paralleled by their effects on adhesion to serum-coated glass. We conclude that granulocyte-endothelial interaction is a complex process, with each cell type responding to the other or to factors produced by it, and that data derived solely from studies of granulocyte adhesion to inert substrata will not always reflect granulocyte-endothelial interaction in vivo.", "contents": "Granulocyte adhesion to endothelium in culture. We previously described a model system for studying the adherence of granulocytes to cultured endothelium, and have now investigated the effects of other blood components on granulocyte adhesion in this system. Red cells enhanced adhesion, whereas blood platelets decreased adhesion, and further experiments suggested that endothelial cells secrete a proadhesive factor, particularly if incubated with plasma. We have also investigated the effects of several drugs, and attempted to localize their sites of action. Flavonoid drugs increased adhesion by an effect at the endothelial cell surface, whereas agents that increase cyclic AMP levels, including several prostaglandins, stimulated adhesion mainly by their effects on granulocytes. The effects of some agents on granulocyte adhesion to endothelium were not paralleled by their effects on adhesion to serum-coated glass. We conclude that granulocyte-endothelial interaction is a complex process, with each cell type responding to the other or to factors produced by it, and that data derived solely from studies of granulocyte adhesion to inert substrata will not always reflect granulocyte-endothelial interaction in vivo."}
{"id": "PMID:230197", "title": "Colchicine-induced paracrystals in the tapetum of wheat anthers.", "content": "Prolonged colchicine treatment induced the formation of numerous cytoplasmic para-crystals in tapetal cells of wheat anthers containing germ line cells at pre-meiotic mitosis or early pre-meiotic interphase. Such paracrystals were up to 8 microns long and 0.7 microns in diameter, and filled up to about 8% of the volume of the cytoplasm. Paracrystals were not bounded by a membrane. A paracrystal consisted of tubules running in parallel with its long axis.  Paracrystals cut at right angles to their long axes revealed hexagonal arrays of circles with a maximum diameter of about 35 nm and electron-dense walls 6--7 nm in thickness. Similar paracrystals were not seen in any cell type of untreated anthers, or in germ line cells of treated anthers, containing stages between pre-meiotic mitosis and first metaphase of meiosis inclusive. The possible significance of the paracrystals in relation to the function of the tapetum is discussed.", "contents": "Colchicine-induced paracrystals in the tapetum of wheat anthers. Prolonged colchicine treatment induced the formation of numerous cytoplasmic para-crystals in tapetal cells of wheat anthers containing germ line cells at pre-meiotic mitosis or early pre-meiotic interphase. Such paracrystals were up to 8 microns long and 0.7 microns in diameter, and filled up to about 8% of the volume of the cytoplasm. Paracrystals were not bounded by a membrane. A paracrystal consisted of tubules running in parallel with its long axis.  Paracrystals cut at right angles to their long axes revealed hexagonal arrays of circles with a maximum diameter of about 35 nm and electron-dense walls 6--7 nm in thickness. Similar paracrystals were not seen in any cell type of untreated anthers, or in germ line cells of treated anthers, containing stages between pre-meiotic mitosis and first metaphase of meiosis inclusive. The possible significance of the paracrystals in relation to the function of the tapetum is discussed."}
{"id": "PMID:230199", "title": "Isolation of the major herpes simplex virus type 1 (HSV-1)-specific glycoprotein by hydroxylapatite chromatography and its use in enzyme-linked immunosorbent assay for titration of human HSV-1-specific antibodies.", "content": "A 131,000 molecular weight herpes simplex virus type 1 (HSV-1) glycoprotein designated antigen number 6 (Ag-6) was previously shown to possess almost exclusively HSV-1-specific antigenic sites. Fused rocket and crossed immunoelectrophoresis of fractions obtained from hydroxylapatite chromatography of crude HSV-1 antigen (Triton X-100-solubilized, infected tissue culture cells) showed that a subfraction of Ag-6 could be separated from the other HSV antigens. Enzyme-linked immunosorbent assay with the isolated Ag-6 showed that sera from rabbits infected with HSV-1 and HSV-1 human antisera contained antibodies to Ag-6, whereas sera from HSV-2-infected rabbits and sera from patients with primary HSV-2 infections did not react with Ag-6. Enzyme-linked immunosorbent assay of 852 human sera for antibodies to HSV type-common glycoproteins, Ag-6, and HSV 2-specific antigens showed that 139 sera which reacted negatively with HSV type-common glycoproteins also did not react with Ag-6 with HSV-2 specific antigens. The 713 sera reacting positively to HSV type-common antigens either reacted with Ag-6 (328 sera) or with HSV-2-specific antigens (31 sera) or both  (354 sera). This means that Ag-6 might be useful in large-scale human serology for the detection of past infection with HSV-1, irrespective of whether or not past infection with HSV-2 has occurred.", "contents": "Isolation of the major herpes simplex virus type 1 (HSV-1)-specific glycoprotein by hydroxylapatite chromatography and its use in enzyme-linked immunosorbent assay for titration of human HSV-1-specific antibodies. A 131,000 molecular weight herpes simplex virus type 1 (HSV-1) glycoprotein designated antigen number 6 (Ag-6) was previously shown to possess almost exclusively HSV-1-specific antigenic sites. Fused rocket and crossed immunoelectrophoresis of fractions obtained from hydroxylapatite chromatography of crude HSV-1 antigen (Triton X-100-solubilized, infected tissue culture cells) showed that a subfraction of Ag-6 could be separated from the other HSV antigens. Enzyme-linked immunosorbent assay with the isolated Ag-6 showed that sera from rabbits infected with HSV-1 and HSV-1 human antisera contained antibodies to Ag-6, whereas sera from HSV-2-infected rabbits and sera from patients with primary HSV-2 infections did not react with Ag-6. Enzyme-linked immunosorbent assay of 852 human sera for antibodies to HSV type-common glycoproteins, Ag-6, and HSV 2-specific antigens showed that 139 sera which reacted negatively with HSV type-common glycoproteins also did not react with Ag-6 with HSV-2 specific antigens. The 713 sera reacting positively to HSV type-common antigens either reacted with Ag-6 (328 sera) or with HSV-2-specific antigens (31 sera) or both  (354 sera). This means that Ag-6 might be useful in large-scale human serology for the detection of past infection with HSV-1, irrespective of whether or not past infection with HSV-2 has occurred."}
{"id": "PMID:230198", "title": "Role of bacterial growth rates in the epidemiology and pathogenesis of urinary infections in women.", "content": "The mean minimum generation time in shake culture in urine of 6 urinary isolates of Escherichia coli (21.7 +/- 0.6 min) was significantly shorter (P = 0.0003) than that of 14 isolates of less common urinary pathogens (46.0 +/- 18.6 min). Mixed populations of approximately equal numbers of E. coli cells paired with other urinary, fecal, and urethral organisms were introduced into a laboratory model of the lower human urinary tract. This model used urine as a medium and reproduced some features of the balance between bacterial growth and the flushing effect of urine. After 24 h E. coli formed greater than or equal to 99% of the bacterial population in the bladder model for 16 our of 18 pairs of isolates examined. Relatively high oxygen tensions in urine sample from 18 healthy women (10.9 +/- 22. kPA) and 18 infected patients (8.0 +/- 4.3 kPa) may explain why anaerobic urinary infections are uncommon. The rapid growth rate of E. coli may be one explanation why it is the commonest cause of urinary infection even though it is relatively uncommon at the urethral meatus.", "contents": "Role of bacterial growth rates in the epidemiology and pathogenesis of urinary infections in women. The mean minimum generation time in shake culture in urine of 6 urinary isolates of Escherichia coli (21.7 +/- 0.6 min) was significantly shorter (P = 0.0003) than that of 14 isolates of less common urinary pathogens (46.0 +/- 18.6 min). Mixed populations of approximately equal numbers of E. coli cells paired with other urinary, fecal, and urethral organisms were introduced into a laboratory model of the lower human urinary tract. This model used urine as a medium and reproduced some features of the balance between bacterial growth and the flushing effect of urine. After 24 h E. coli formed greater than or equal to 99% of the bacterial population in the bladder model for 16 our of 18 pairs of isolates examined. Relatively high oxygen tensions in urine sample from 18 healthy women (10.9 +/- 22. kPA) and 18 infected patients (8.0 +/- 4.3 kPa) may explain why anaerobic urinary infections are uncommon. The rapid growth rate of E. coli may be one explanation why it is the commonest cause of urinary infection even though it is relatively uncommon at the urethral meatus."}
{"id": "PMID:230200", "title": "Evaluation of enzyme-linked immunosorbent assay for the serodiagnosis of amebiasis.", "content": "This report describes the development and evaluation of an enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies to Entamoeba histolytica. Highly sensitive and reproducible results were obtained in antigen-coated plates prepared by air-drying at 37 degrees C. Comparison of the ELISA with indirect fluorescent antibody and indirect hemagglutination techniques showed that the former was slightly more sensitive than the two latter methods. The specificity was evaluated by testing specially chosen population groups. ELISA was negative in 96.4% of 693 normal adults and children and in 96.6% of 377 patients with various parasitic, bacterial, mycotic, and other clinical diseases. The assay was positive in 26% of 461 patients with suspected amebiasis and in all of 53 patients with amoebic liver abscess. The ELISA was found to be a specific, highly sensitive, and reliable procedure for detecting anti-E. histolytica antibodies in humans.", "contents": "Evaluation of enzyme-linked immunosorbent assay for the serodiagnosis of amebiasis. This report describes the development and evaluation of an enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies to Entamoeba histolytica. Highly sensitive and reproducible results were obtained in antigen-coated plates prepared by air-drying at 37 degrees C. Comparison of the ELISA with indirect fluorescent antibody and indirect hemagglutination techniques showed that the former was slightly more sensitive than the two latter methods. The specificity was evaluated by testing specially chosen population groups. ELISA was negative in 96.4% of 693 normal adults and children and in 96.6% of 377 patients with various parasitic, bacterial, mycotic, and other clinical diseases. The assay was positive in 26% of 461 patients with suspected amebiasis and in all of 53 patients with amoebic liver abscess. The ELISA was found to be a specific, highly sensitive, and reliable procedure for detecting anti-E. histolytica antibodies in humans."}
{"id": "PMID:230201", "title": "Center for Disease Control Diagnostic Immunology Proficiency Testing Program results for 1978.", "content": "Data from about 1,000 laboratories participating in the Diagnostic Immunology portion of the 1978 Center for Disease Control Proficiency Testing Program provided information dealing with laboratory performance and trends in testing protocols. Ninety specimens were distributed in scheduled quarterly and semiannual shipments, and five additional specimens were provided in a special survey. The specimens offered both qualitative and quantitative challenges for a wide variety of analytes which included syphilis serology, rheumatoid factor, bacterial agglutinins, hepatitis B surface antigen, immunoglobulins and other serum proteins, infectious mononucleosis, rubella, toxoplasma, antinuclear antibodies, and streptococcal exoenzymes. This paper summarizes the results of the 1978 program.", "contents": "Center for Disease Control Diagnostic Immunology Proficiency Testing Program results for 1978. Data from about 1,000 laboratories participating in the Diagnostic Immunology portion of the 1978 Center for Disease Control Proficiency Testing Program provided information dealing with laboratory performance and trends in testing protocols. Ninety specimens were distributed in scheduled quarterly and semiannual shipments, and five additional specimens were provided in a special survey. The specimens offered both qualitative and quantitative challenges for a wide variety of analytes which included syphilis serology, rheumatoid factor, bacterial agglutinins, hepatitis B surface antigen, immunoglobulins and other serum proteins, infectious mononucleosis, rubella, toxoplasma, antinuclear antibodies, and streptococcal exoenzymes. This paper summarizes the results of the 1978 program."}
{"id": "PMID:230202", "title": "Diagnostic ultrasound in breast cancer: analysis of retrotumorous echo patterns correlated with sonic attenuation by cancerous connective tissue.", "content": "Echocardiographic diagnosis of breast cancer has been used in clinical medicine for the past several years. Echographic findings and characteristics suggesting differentiation between malignant and benign tumors have been reported by various investigators. These signs are analysed in correlation with histological findings, especially cancerous connective tissue and nonconnective tissue and retrotumorous shadow patterns in clinical echograms of various breast cancers. Special reference is made to ultrasound attenuation related to bioacoustical tissue characteristics. This casual mechanism provides a stepping-stone for further improvements in ultrasound apparatus designed for clinical diagnosis of breast cancer. Furthermore, it may stimulate basic research on the bioacoustical properties of ultrasound reflection, absorption, and velocity.", "contents": "Diagnostic ultrasound in breast cancer: analysis of retrotumorous echo patterns correlated with sonic attenuation by cancerous connective tissue. Echocardiographic diagnosis of breast cancer has been used in clinical medicine for the past several years. Echographic findings and characteristics suggesting differentiation between malignant and benign tumors have been reported by various investigators. These signs are analysed in correlation with histological findings, especially cancerous connective tissue and nonconnective tissue and retrotumorous shadow patterns in clinical echograms of various breast cancers. Special reference is made to ultrasound attenuation related to bioacoustical tissue characteristics. This casual mechanism provides a stepping-stone for further improvements in ultrasound apparatus designed for clinical diagnosis of breast cancer. Furthermore, it may stimulate basic research on the bioacoustical properties of ultrasound reflection, absorption, and velocity."}
{"id": "PMID:230203", "title": "EB virus-specific IgA in serum of patients with infectious mononucleosis and of healthy people of different ages.", "content": "The following sera were tested for EB virus-specific IgA: serial sera from 61 cases of infectious mononucleosis (IM) and from 195 EBV IgG positive healthy students; single sera from each of 1469 persons of different ages, 63 cases of untreated Hodgkin's disease, and 22 neonates. EBV specific IgA was found in the sera from 88% of cases of IM, from 18.5% of EBV IgG positive healthy students, and in 13.5% of repeat samples from the same students three years later. The incidence of EBV IgA varied from 5 to 30% at different ages in single sera from EBV IgG positive persons aged 2 to 70 years. The higher percentages occurred in the age groups where recent sero-conversion rates were high. Fifteen percent of sera from cases of Hodgkin's disease were positive for EBV IgA, an incidence similar to that for healthy adults in the age group 25-45 years. None of the EBV IgG positive sera from neonates gave a positive reaction for EBV IGA.", "contents": "EB virus-specific IgA in serum of patients with infectious mononucleosis and of healthy people of different ages. The following sera were tested for EB virus-specific IgA: serial sera from 61 cases of infectious mononucleosis (IM) and from 195 EBV IgG positive healthy students; single sera from each of 1469 persons of different ages, 63 cases of untreated Hodgkin's disease, and 22 neonates. EBV specific IgA was found in the sera from 88% of cases of IM, from 18.5% of EBV IgG positive healthy students, and in 13.5% of repeat samples from the same students three years later. The incidence of EBV IgA varied from 5 to 30% at different ages in single sera from EBV IgG positive persons aged 2 to 70 years. The higher percentages occurred in the age groups where recent sero-conversion rates were high. Fifteen percent of sera from cases of Hodgkin's disease were positive for EBV IgA, an incidence similar to that for healthy adults in the age group 25-45 years. None of the EBV IgG positive sera from neonates gave a positive reaction for EBV IGA."}
{"id": "PMID:230204", "title": "Ribosome lamella complex in neoplastic cells of a S\u00e9zary's syndrome.", "content": "The first case of ribosome lamella complex (RLC) is reported in abnormal cells of a S\u00e9zary's syndrome, a T cell malignancy. Until now this ultrastructural cytoplasmic inclusion has usually been described in hairy cell leukaemia and other lymphoproliferative syndromes of B cell origin. Since RLC are also observed in abnormal lymphoid T cells, in non lymphoid cells, and moreover in non haematopoietic cells, they lack diagnostic specificity.", "contents": "Ribosome lamella complex in neoplastic cells of a S\u00e9zary's syndrome. The first case of ribosome lamella complex (RLC) is reported in abnormal cells of a S\u00e9zary's syndrome, a T cell malignancy. Until now this ultrastructural cytoplasmic inclusion has usually been described in hairy cell leukaemia and other lymphoproliferative syndromes of B cell origin. Since RLC are also observed in abnormal lymphoid T cells, in non lymphoid cells, and moreover in non haematopoietic cells, they lack diagnostic specificity."}
{"id": "PMID:230205", "title": "Plasma and urine cyclic nucleotide levels in malignant disease and cirrhosis of the liver.", "content": "Plasma and 24-hour urinary cyclic AMP and cyclic GMP levels were determined by saturation analysis in specimens from normal subjects and from 101 patients with tumours of the gastrointestinal tract, breast, lung, bladder or prostate, or with cirrhosis of the liver. Relative to 46 control subjects, plasma cyclic GMP concentrations were significantly elevated in seven patients with gastric tumours, 20 patients with cancer of the breast, six patients with lung cancer, and 12 patients with cirrhosis of the liver. Urinary cyclic GMP/creatinine ratios were significantly increased in cirrhotic patients and in the lung and oesophageal cancer groups. In no cancer group were increases in plasma or urine cyclic GMP levels sufficiently consistent to be of value in the diagnosis of human malignant disease. Changes in extracellular fluid cyclic nucleotide levels in the cirrhotic group were very similar to those that have been reported for primary hepatoma patients.", "contents": "Plasma and urine cyclic nucleotide levels in malignant disease and cirrhosis of the liver. Plasma and 24-hour urinary cyclic AMP and cyclic GMP levels were determined by saturation analysis in specimens from normal subjects and from 101 patients with tumours of the gastrointestinal tract, breast, lung, bladder or prostate, or with cirrhosis of the liver. Relative to 46 control subjects, plasma cyclic GMP concentrations were significantly elevated in seven patients with gastric tumours, 20 patients with cancer of the breast, six patients with lung cancer, and 12 patients with cirrhosis of the liver. Urinary cyclic GMP/creatinine ratios were significantly increased in cirrhotic patients and in the lung and oesophageal cancer groups. In no cancer group were increases in plasma or urine cyclic GMP levels sufficiently consistent to be of value in the diagnosis of human malignant disease. Changes in extracellular fluid cyclic nucleotide levels in the cirrhotic group were very similar to those that have been reported for primary hepatoma patients."}
{"id": "PMID:230209", "title": "Desensitization of beta-adrenergic stimulated adenylate cyclase in turkey erythrocytes.", "content": "Desensitization of catecholamine stimulated adenylate cyclase (AC) activity is demonstrated in membranes derived from turkey erythrocytes pre-treated with isoproterenol. Membranes from desensitized cells had a loss in maximal catecholamine stimulated adenylate cyclase activity of 104 +/- 13 (pmols/mg protein/10', p less than .001) compared with controls. When adenylate cyclase was maximally stimulated with NaF or Gpp(NH)p, the decrements were 84 +/- 19 (p less than .005) and 92 +/- 32 (p less than .05) pmol/mg protein/10' respectively. There was no change in beta-adrenergic receptor number in membranes derived from treated cells. While the molecular mechanism accounting for the desensitization is uncertain, the data is consistent with the hypothesis that there is a lesion distal to the beta-adrenergic receptor, possibly involving the nucleotide site or the catalytic subunit of adenylate cyclase, causing the desensitization in the isoproterenol treated cells.", "contents": "Desensitization of beta-adrenergic stimulated adenylate cyclase in turkey erythrocytes. Desensitization of catecholamine stimulated adenylate cyclase (AC) activity is demonstrated in membranes derived from turkey erythrocytes pre-treated with isoproterenol. Membranes from desensitized cells had a loss in maximal catecholamine stimulated adenylate cyclase activity of 104 +/- 13 (pmols/mg protein/10', p less than .001) compared with controls. When adenylate cyclase was maximally stimulated with NaF or Gpp(NH)p, the decrements were 84 +/- 19 (p less than .005) and 92 +/- 32 (p less than .05) pmol/mg protein/10' respectively. There was no change in beta-adrenergic receptor number in membranes derived from treated cells. While the molecular mechanism accounting for the desensitization is uncertain, the data is consistent with the hypothesis that there is a lesion distal to the beta-adrenergic receptor, possibly involving the nucleotide site or the catalytic subunit of adenylate cyclase, causing the desensitization in the isoproterenol treated cells."}
{"id": "PMID:230210", "title": "Cyclic nucleotide levels in rat embryo fibroblasts treated with tumor-promoting phorbol diester.", "content": "Intracellular concentrations of cyclic adenosine 3':5'-monophosphate (cyclic AMP) and cyclic guanosine 3':5'-monophosphate were measured in rat embryo fibroblasts stimulated to divide by either the addition of 12-0-tetradecanoyl phorbol-13-acetate (TPA) or a serum-supplemented medium change. Cyclic nucleotide levels were altered within minutes and large oscillations occurred in a reciprocal fashion over the pre-replicative and the replicative phases. Patterns of oscillating levels depended on the growth state of the cultures. Intracellular content of cyclic nucleotide similarly changed in response to either mitogenic treatment with the exception of the early alterations in cyclic AMP. The medium-change stimulation resulted within minutes in a drop of the cyclic AMP levels at confluence and a rise in growing cells when TPA-induced stimulation proceeded without altering those levels. Treatment with 4-0-methyl-phorbol didecanoate, a TPA derivative that is inactive as a tumor promoter, did not affect the cyclic nucleotide levels.", "contents": "Cyclic nucleotide levels in rat embryo fibroblasts treated with tumor-promoting phorbol diester. Intracellular concentrations of cyclic adenosine 3':5'-monophosphate (cyclic AMP) and cyclic guanosine 3':5'-monophosphate were measured in rat embryo fibroblasts stimulated to divide by either the addition of 12-0-tetradecanoyl phorbol-13-acetate (TPA) or a serum-supplemented medium change. Cyclic nucleotide levels were altered within minutes and large oscillations occurred in a reciprocal fashion over the pre-replicative and the replicative phases. Patterns of oscillating levels depended on the growth state of the cultures. Intracellular content of cyclic nucleotide similarly changed in response to either mitogenic treatment with the exception of the early alterations in cyclic AMP. The medium-change stimulation resulted within minutes in a drop of the cyclic AMP levels at confluence and a rise in growing cells when TPA-induced stimulation proceeded without altering those levels. Treatment with 4-0-methyl-phorbol didecanoate, a TPA derivative that is inactive as a tumor promoter, did not affect the cyclic nucleotide levels."}
{"id": "PMID:230211", "title": "A new chromatographic method using immobilized acriflavin for measuring cyclic AMP in cells prelabeled with radioactive adenine.", "content": "A method using the principle of charge-transfer chromatography has been developed for the determination of cyclic AMP levels in intact prelabeled cells. The ATP pool was prelabeled by incubating the cells in the presence of radioactive adenine. The cyclic AMP formed from ATP was extracted with HC10(4) and separated from adenine and other adenosine-related nucleotides by chromatography on acriflavin-Sephadex G-25. This method provides a rapid and sensitive isolation of cyclic AMP with high recovery (95-100%) and low blnks. Further, no contamination of the cyclic AMP fractions was found by either adenine or adenosine nucleotides such as ATP, ADP or AMP. This procedure is applicable to a variety of cell or tissue systems.", "contents": "A new chromatographic method using immobilized acriflavin for measuring cyclic AMP in cells prelabeled with radioactive adenine. A method using the principle of charge-transfer chromatography has been developed for the determination of cyclic AMP levels in intact prelabeled cells. The ATP pool was prelabeled by incubating the cells in the presence of radioactive adenine. The cyclic AMP formed from ATP was extracted with HC10(4) and separated from adenine and other adenosine-related nucleotides by chromatography on acriflavin-Sephadex G-25. This method provides a rapid and sensitive isolation of cyclic AMP with high recovery (95-100%) and low blnks. Further, no contamination of the cyclic AMP fractions was found by either adenine or adenosine nucleotides such as ATP, ADP or AMP. This procedure is applicable to a variety of cell or tissue systems."}
{"id": "PMID:230213", "title": "Posterior segment involvement in selected pediatric infectious diseases.", "content": "This paper reviews the ocular manifestations that may be found primarily in the posterior segment of the eye in selected infectious diseases. These diseases largely affect the pediatric population. Each disease is discussed in terms of its etiology, epidemiology, clinical course and manifestations, ocular involvement, and treatment. These diseases are important since their ocular involvement may lead to severe visual impairment.", "contents": "Posterior segment involvement in selected pediatric infectious diseases. This paper reviews the ocular manifestations that may be found primarily in the posterior segment of the eye in selected infectious diseases. These diseases largely affect the pediatric population. Each disease is discussed in terms of its etiology, epidemiology, clinical course and manifestations, ocular involvement, and treatment. These diseases are important since their ocular involvement may lead to severe visual impairment."}
{"id": "PMID:230214", "title": "Anterior segment and external ocular manifestations of infectious diseases in children.", "content": "Anterior segment and external ocular manifestations of some infectious diseases which are particularly important to patients of the pediatric age group are discussed. A brief review of the various systemic diseases is given along with the ocular findings. Approaches to diagnosis, therapy, and management of both the systemic and ocular components of the illnesses are included.", "contents": "Anterior segment and external ocular manifestations of infectious diseases in children. Anterior segment and external ocular manifestations of some infectious diseases which are particularly important to patients of the pediatric age group are discussed. A brief review of the various systemic diseases is given along with the ocular findings. Approaches to diagnosis, therapy, and management of both the systemic and ocular components of the illnesses are included."}
{"id": "PMID:230215", "title": "[Study of uveal malignant melanoma with the electron microscope (author's transl)].", "content": "Twelve cases of uveal malignant melanoma, including the principal histologic types of this neoplasm according to Callender, were studied with the electron microscope. Nuclear inclusions were observed in each case, more frequently in epithelioid cells: they were probably correlated with nuclear hyperactivity. Melanogenesis in neoplastic cells was sometimes abnormal because of the granular structure of the premelanosomes, of the difference in size and in shape melanosomes, of the difference in size and in shape of the pigment granules and of the different stage of evolution of the premelanosomes in the cell. The size and the degree of reticulation of nucleoli and the number of free ribosomes and mitochondria increased from spindle A, to spindle B and epithelioid cells. This behaviour probably depends on an increasing metabolic activity which is related to the increasing degree of malignancy.", "contents": "[Study of uveal malignant melanoma with the electron microscope (author's transl)]. Twelve cases of uveal malignant melanoma, including the principal histologic types of this neoplasm according to Callender, were studied with the electron microscope. Nuclear inclusions were observed in each case, more frequently in epithelioid cells: they were probably correlated with nuclear hyperactivity. Melanogenesis in neoplastic cells was sometimes abnormal because of the granular structure of the premelanosomes, of the difference in size and in shape melanosomes, of the difference in size and in shape of the pigment granules and of the different stage of evolution of the premelanosomes in the cell. The size and the degree of reticulation of nucleoli and the number of free ribosomes and mitochondria increased from spindle A, to spindle B and epithelioid cells. This behaviour probably depends on an increasing metabolic activity which is related to the increasing degree of malignancy."}
{"id": "PMID:230257", "title": "Dynamic assay of enzyme activities in single cells by flow cytometry.", "content": "Three enzymes in single cells were assayed dynamically by flow cytometry using four fluorogenic substrates. Acid phosphatase was determined with 7-bromo-3-hydroxy-2-naphtho-o-anisidine (naphthol AS-BI) phosphate and 4-methylumbelliferone (MU) phosphate, neutral esterase with fluorescein diacetate, and lactic dehydrogenase with NAD-sodium lactate. Fluorescence measurements obtained with the flow cytometer were converted into relative specific enzyme activities for single cells with molar fluorescence coefficients determined with a spectrofluorometer. Specific activities obtained from spectrofluorometric data were compared with activities calculated from flow cytometeric data. Flow cytometric assays gave lower specific single cell activities for 4-methylumbelliferone phosphate hydrolysis and for lactic dehydrogenase than did similar assays by standard spectrofluorometry. Product diffusion may be the greatest cause for this discrepancy.", "contents": "Dynamic assay of enzyme activities in single cells by flow cytometry. Three enzymes in single cells were assayed dynamically by flow cytometry using four fluorogenic substrates. Acid phosphatase was determined with 7-bromo-3-hydroxy-2-naphtho-o-anisidine (naphthol AS-BI) phosphate and 4-methylumbelliferone (MU) phosphate, neutral esterase with fluorescein diacetate, and lactic dehydrogenase with NAD-sodium lactate. Fluorescence measurements obtained with the flow cytometer were converted into relative specific enzyme activities for single cells with molar fluorescence coefficients determined with a spectrofluorometer. Specific activities obtained from spectrofluorometric data were compared with activities calculated from flow cytometeric data. Flow cytometric assays gave lower specific single cell activities for 4-methylumbelliferone phosphate hydrolysis and for lactic dehydrogenase than did similar assays by standard spectrofluorometry. Product diffusion may be the greatest cause for this discrepancy."}
{"id": "PMID:230259", "title": "Subpopulation of peripheral blood lymphocytes in human encephalitis caused by group B arboviruses (Dengue, West Nile and Japanese B encephalitis.", "content": "Sera from twenty patients with clinically diagnosed viral encephalitis were studied during the acute and convalescent phases of illness for evidence of group B arboviral infection by demonstrating a rise in the titre of haemagglutination inhibiting (HI) antibodies. The immune status of these individuals was studied by quantitating peripheral T, T and 'null' lymphocytes. The percentage of total T cells in arboviral encephalitic (AE) group decreased significantly while that of B cells and 'active' T cells remained unaltered when compared to that of normal individuals. The null cell percentage, on the other hand increased significantly in the AE group. The absolute number of circulating T and B cells did not alter in the AE group while that of null cells rose significantly. The percentage and concentration of T. B and null cells during the convalescent phase of AE did not differ significantly when compared to those of the acute phase.", "contents": "Subpopulation of peripheral blood lymphocytes in human encephalitis caused by group B arboviruses (Dengue, West Nile and Japanese B encephalitis. Sera from twenty patients with clinically diagnosed viral encephalitis were studied during the acute and convalescent phases of illness for evidence of group B arboviral infection by demonstrating a rise in the titre of haemagglutination inhibiting (HI) antibodies. The immune status of these individuals was studied by quantitating peripheral T, T and 'null' lymphocytes. The percentage of total T cells in arboviral encephalitic (AE) group decreased significantly while that of B cells and 'active' T cells remained unaltered when compared to that of normal individuals. The null cell percentage, on the other hand increased significantly in the AE group. The absolute number of circulating T and B cells did not alter in the AE group while that of null cells rose significantly. The percentage and concentration of T. B and null cells during the convalescent phase of AE did not differ significantly when compared to those of the acute phase."}
{"id": "PMID:230260", "title": "Reactivity of ACTH and synthetic ACTH peptides with antisera to human calcitonin.", "content": "We studied reactivity of highly purified pituitary hormones in our human calcitonin (hCT) radioimmunoassay (RIA) which can detect 1 pg of hCT. ACTH at doses of greater than 1 microgram of peptide per RIA tube reacted in the hCT assay, as did beta-endorphin (beta EPH) at a dose of 10 micrograms per tube. No reactivity was observed with comparable concentrations of all other known pituitary hormones. ACTH also reacted at doses greater than 1 microgram per tube with 7 other hCT antisera which recognized differing antigenic determinants in the calcitonin molecule but it was not reactive with 2 antisera against porcine calcitonin or 2 antisera against salmon calcitonin. This slight degree of cross-reactivity of hACTH and beta EPH in the hCT RIA cannot account for the presence of immunoreactive CT in pituitary glands. Nevertheless, antisera used for the localization of peptides must be rigorously tested for the existence of cross-reactivities with other possible substances, especially if such antisera detect the peptide in unexpected tissues.", "contents": "Reactivity of ACTH and synthetic ACTH peptides with antisera to human calcitonin. We studied reactivity of highly purified pituitary hormones in our human calcitonin (hCT) radioimmunoassay (RIA) which can detect 1 pg of hCT. ACTH at doses of greater than 1 microgram of peptide per RIA tube reacted in the hCT assay, as did beta-endorphin (beta EPH) at a dose of 10 micrograms per tube. No reactivity was observed with comparable concentrations of all other known pituitary hormones. ACTH also reacted at doses greater than 1 microgram per tube with 7 other hCT antisera which recognized differing antigenic determinants in the calcitonin molecule but it was not reactive with 2 antisera against porcine calcitonin or 2 antisera against salmon calcitonin. This slight degree of cross-reactivity of hACTH and beta EPH in the hCT RIA cannot account for the presence of immunoreactive CT in pituitary glands. Nevertheless, antisera used for the localization of peptides must be rigorously tested for the existence of cross-reactivities with other possible substances, especially if such antisera detect the peptide in unexpected tissues."}
{"id": "PMID:230261", "title": "'Aspira': a new sensitive assay for the detection of hepatitis B surface antigen.", "content": "A sensitive method for the detection of hepatitis B surface antigen (HBsAg) is described whereby the separation of specific antibody by affinity chromatography is incorporated into one of the assay reagents. HBsAg, which may be obtained from tissue culture fluids of a human hepatoma cell line, is first reacted with polystyrene beads. Unoccupied spaces on the plastic are next covered with a non-specific protein (e.g. albumin). The plastic is then reacted with either whole antiserum or an IgG fraction of anti-HBs. Care must be taken to cover all of the reacting sites of the first layer of HBsAg with sufficient anti-HBs. This results in a reagent of detecting antigen. No affinity purified antibody was necessary because the reagent, at this stage, contains only specific antibody on the surface. Antigen reacting with this reagent can be detected by the addition of radioactively labeled IgG fraction of anti-HBs, which will complete the 'sandwich'. This assay has been evaluated and found to be as sensitive as those commerically available.", "contents": "'Aspira': a new sensitive assay for the detection of hepatitis B surface antigen. A sensitive method for the detection of hepatitis B surface antigen (HBsAg) is described whereby the separation of specific antibody by affinity chromatography is incorporated into one of the assay reagents. HBsAg, which may be obtained from tissue culture fluids of a human hepatoma cell line, is first reacted with polystyrene beads. Unoccupied spaces on the plastic are next covered with a non-specific protein (e.g. albumin). The plastic is then reacted with either whole antiserum or an IgG fraction of anti-HBs. Care must be taken to cover all of the reacting sites of the first layer of HBsAg with sufficient anti-HBs. This results in a reagent of detecting antigen. No affinity purified antibody was necessary because the reagent, at this stage, contains only specific antibody on the surface. Antigen reacting with this reagent can be detected by the addition of radioactively labeled IgG fraction of anti-HBs, which will complete the 'sandwich'. This assay has been evaluated and found to be as sensitive as those commerically available."}
{"id": "PMID:230263", "title": "H-2 and non-H-2 determined strain variation in palatal shelf and tongue adenosine 3':5' cyclic monophosphate: a possible role in the etiology of steroid-induced cleft palate.", "content": "The concentration of cAMP was measured in palatal shelves and tongues of 14.5-day old foetuses, 14.5-day old foetuses from steroid treated mothers, and 15.5-day old foetuses from four inbred lines of mice which represent the four possible combinations of two H-2 alleles and two residual genetic backgrounds. The incidence of spontaneous and steroid-induced cleft palate in these four strains was also determined. Analyses of variance of the cAMP data reveal that both the H-2 region and residual genetic background determine cAMP concentrations in both tissues and on both days of development. Similar analyses of cAMP concentrations after steroid treatments of the mother indicate that the interaction between H-2 and residual genetic background is significantly different in the injected than in the uninjected mice in both palatal shelves and tongues. The incidence of steroid-induced cleft palate parallels the palatal shelf concentration of cAMP before steroid treatment of the mother with one exception. These data suggest that a portion of the H-2 controlled component of susceptibility to steroid-induced cleft palate is mediated through alterations in the metabolism of cAMP.", "contents": "H-2 and non-H-2 determined strain variation in palatal shelf and tongue adenosine 3':5' cyclic monophosphate: a possible role in the etiology of steroid-induced cleft palate. The concentration of cAMP was measured in palatal shelves and tongues of 14.5-day old foetuses, 14.5-day old foetuses from steroid treated mothers, and 15.5-day old foetuses from four inbred lines of mice which represent the four possible combinations of two H-2 alleles and two residual genetic backgrounds. The incidence of spontaneous and steroid-induced cleft palate in these four strains was also determined. Analyses of variance of the cAMP data reveal that both the H-2 region and residual genetic background determine cAMP concentrations in both tissues and on both days of development. Similar analyses of cAMP concentrations after steroid treatments of the mother indicate that the interaction between H-2 and residual genetic background is significantly different in the injected than in the uninjected mice in both palatal shelves and tongues. The incidence of steroid-induced cleft palate parallels the palatal shelf concentration of cAMP before steroid treatment of the mother with one exception. These data suggest that a portion of the H-2 controlled component of susceptibility to steroid-induced cleft palate is mediated through alterations in the metabolism of cAMP."}
{"id": "PMID:230266", "title": "The effect of cholesterol feeding on bile acid kinetics and biliary lipids in normolipidemic and hypertriglyceridemic subjects.", "content": "Six normolipidemic and six hypertriglyceridemic subjects were studied. The investigations were conducted before and after the basal diet (cholesterol intake about 0.8 mmol/day) was replaced by a cholesterol-rich diet (cholesterol intake about 4 mmol/day). Irrespective of the type of diet, the combined formation of cholic acid (C) and chenodeoxycholic acid (CD) was about two times higher in the hyperlipoproteinemic (mostly type IV) than the normolipidemic subjects. With the cholesterol-rich diet, the total plasma cholesterol increased in all normolipidemic and in four hyperlipidemic patients. Although total bile acid formation remained constant, there were several indications that an augmented intake of dietary cholesterol influenced bile acid metabolism. The pool size of CD increased in all but one normolipidemic subject. This group also displayed a decrease in the C/CD ratio of the bile acids produced and in the C/CD ratio of the bile acids in duodenal bile. The latter finding was also encountered in the hyperlipoproteinemic patients. On the basis of these and other data, it is suggested that the pattern of the bile acids synthesized may roughly reflect the degree of hepatic cholesterogenesis. Cholesterol feeding had no consistent effects on the molar cholesterol concentration in duodenal bile.-Anders\u00e9n, E., and K. Hellstr\u00f6m. The effect of cholesterol feeding on bile acid kinetics and biliary lipids in normolipidemic and hypertriglyceridemic subjects.", "contents": "The effect of cholesterol feeding on bile acid kinetics and biliary lipids in normolipidemic and hypertriglyceridemic subjects. Six normolipidemic and six hypertriglyceridemic subjects were studied. The investigations were conducted before and after the basal diet (cholesterol intake about 0.8 mmol/day) was replaced by a cholesterol-rich diet (cholesterol intake about 4 mmol/day). Irrespective of the type of diet, the combined formation of cholic acid (C) and chenodeoxycholic acid (CD) was about two times higher in the hyperlipoproteinemic (mostly type IV) than the normolipidemic subjects. With the cholesterol-rich diet, the total plasma cholesterol increased in all normolipidemic and in four hyperlipidemic patients. Although total bile acid formation remained constant, there were several indications that an augmented intake of dietary cholesterol influenced bile acid metabolism. The pool size of CD increased in all but one normolipidemic subject. This group also displayed a decrease in the C/CD ratio of the bile acids produced and in the C/CD ratio of the bile acids in duodenal bile. The latter finding was also encountered in the hyperlipoproteinemic patients. On the basis of these and other data, it is suggested that the pattern of the bile acids synthesized may roughly reflect the degree of hepatic cholesterogenesis. Cholesterol feeding had no consistent effects on the molar cholesterol concentration in duodenal bile.-Anders\u00e9n, E., and K. Hellstr\u00f6m. The effect of cholesterol feeding on bile acid kinetics and biliary lipids in normolipidemic and hypertriglyceridemic subjects."}
{"id": "PMID:230267", "title": "Characterization of the multiple-chamber perifused fat cell system.", "content": "A multiple-chamber perifused fat cell system is described. Six chambers containing fat cells were perifused in parallel with buffer. Perifusate was collected for assay of glycerol as an index of lipolytic rates and cells in each chamber can be taken for analysis of biochemical intermediates. The system is so designed that drugs can be infused into the buffer and equally distributed in each chamber or can be individually infused into the buffer to one chamber, allowing for six different conditions to be tested in the same population of fat cells. The time and distribution characteristics of infused material are described. Time relationships are described for isoproterenol and glycerol release and for cyclic AMP levels in the fat cells, and the dose-response relationship between isoproterenol and glycerol release is shown.", "contents": "Characterization of the multiple-chamber perifused fat cell system. A multiple-chamber perifused fat cell system is described. Six chambers containing fat cells were perifused in parallel with buffer. Perifusate was collected for assay of glycerol as an index of lipolytic rates and cells in each chamber can be taken for analysis of biochemical intermediates. The system is so designed that drugs can be infused into the buffer and equally distributed in each chamber or can be individually infused into the buffer to one chamber, allowing for six different conditions to be tested in the same population of fat cells. The time and distribution characteristics of infused material are described. Time relationships are described for isoproterenol and glycerol release and for cyclic AMP levels in the fat cells, and the dose-response relationship between isoproterenol and glycerol release is shown."}
{"id": "PMID:230268", "title": "Acute control of fatty acid synthesis by cyclic AMP in the chick liver cell: possible site of inhibition of citrate formation.", "content": "Glucagon and N,(6)O(2)-dibutyryl cyclic adenosine 3',5'-cyclic monophosphate (Bt(2)cAMP) inhibit fatty acid synthesis from acetate by more than 90% and prevent citrate formation in chick hepatocytes metabolizing glucose. With substrates that enter glycolysis at or below triose-phosphates, e.g., fructose, lactate, or pyruvate, Bt(2)cAMP has no effect on the citrate level and its inhibitory effect on fatty acid synthesis is substantially reversed. Because acetyl-CoA carboxylase requires a tricarboxylic acid activator for activity, it is proposed that regulation of fatty acid synthesis by Bt(2)cAMP is due, in part, to changes in the citrate level. Reduced citrate formation appears to result from a cAMP-induced inhibition of glycolysis. Bt(2)cAMP inhibits (14)CO(2) production from [1-(14)C]-, [6-(14)C]-, and [U-(14)C]glucose and has little effect on (14)CO(2) formation from [1-(14)C]- or [2-(14)C]pyruvate or from [1-(14)C]fructose. [(14)C]Lactate formation from glucose is depressed 50% by Bt(2)cAMP. In the presence of an inhibitor of mitochondrial pyruvate transport lactate accumulation is enhanced, but continues to be lowered 50% by Bt(2)cAMP. The activity of phosphofructokinase is greatly decreased in Bt(2)cAMP-treated cells while the activities of pyruvate kinase and acetyl-CoA carboxylase are unaffected. It appears that decreased glycolytic flux and decreased citrate formation result from depressed phosphofructokinase activity. Fatty acid synthesis from [(14)C]acetate is partially inhibited by Bt(2)cAMP in the presence of fructose, lactate, and pyruvate despite a high citrate level. Incorporation of [(14)C]fructose, [(14)C]pyruvate, or [(14)C]lactate into fatty acids is similarly depressed by Bt(2)cAMP. Synthesis of cholesterol from [(14)C]acetate or [2-(14)C]pyruvate is unaffected by Bt(2)cAMP. These results implicate a second site of inhibition of fatty acid synthesis by Bt(2)cAMP that involves the utilization, but not the production, of cytoplasmic acetyl-CoA.-Clarke, S. D., P. A. Watkins, and M. D. Lane. Acute control of fatty acid synthesis by cyclic AMP in the chick liver cell: possible site of inhibition of citrate formation.", "contents": "Acute control of fatty acid synthesis by cyclic AMP in the chick liver cell: possible site of inhibition of citrate formation. Glucagon and N,(6)O(2)-dibutyryl cyclic adenosine 3',5'-cyclic monophosphate (Bt(2)cAMP) inhibit fatty acid synthesis from acetate by more than 90% and prevent citrate formation in chick hepatocytes metabolizing glucose. With substrates that enter glycolysis at or below triose-phosphates, e.g., fructose, lactate, or pyruvate, Bt(2)cAMP has no effect on the citrate level and its inhibitory effect on fatty acid synthesis is substantially reversed. Because acetyl-CoA carboxylase requires a tricarboxylic acid activator for activity, it is proposed that regulation of fatty acid synthesis by Bt(2)cAMP is due, in part, to changes in the citrate level. Reduced citrate formation appears to result from a cAMP-induced inhibition of glycolysis. Bt(2)cAMP inhibits (14)CO(2) production from [1-(14)C]-, [6-(14)C]-, and [U-(14)C]glucose and has little effect on (14)CO(2) formation from [1-(14)C]- or [2-(14)C]pyruvate or from [1-(14)C]fructose. [(14)C]Lactate formation from glucose is depressed 50% by Bt(2)cAMP. In the presence of an inhibitor of mitochondrial pyruvate transport lactate accumulation is enhanced, but continues to be lowered 50% by Bt(2)cAMP. The activity of phosphofructokinase is greatly decreased in Bt(2)cAMP-treated cells while the activities of pyruvate kinase and acetyl-CoA carboxylase are unaffected. It appears that decreased glycolytic flux and decreased citrate formation result from depressed phosphofructokinase activity. Fatty acid synthesis from [(14)C]acetate is partially inhibited by Bt(2)cAMP in the presence of fructose, lactate, and pyruvate despite a high citrate level. Incorporation of [(14)C]fructose, [(14)C]pyruvate, or [(14)C]lactate into fatty acids is similarly depressed by Bt(2)cAMP. Synthesis of cholesterol from [(14)C]acetate or [2-(14)C]pyruvate is unaffected by Bt(2)cAMP. These results implicate a second site of inhibition of fatty acid synthesis by Bt(2)cAMP that involves the utilization, but not the production, of cytoplasmic acetyl-CoA.-Clarke, S. D., P. A. Watkins, and M. D. Lane. Acute control of fatty acid synthesis by cyclic AMP in the chick liver cell: possible site of inhibition of citrate formation."}
{"id": "PMID:230269", "title": "Receptor-mediated low density lipoprotein catabolism in man.", "content": "Binding of human low density lipoproteins (LDL) to their specific receptor on cultured cells can be inhibited by treatment with 1,2-cyclohexanedione which blocks a number of functionally significant arginyl residues on the apolipoprotein. We have used this observation to examine the role of the receptor pathway in LDL catabolism in man. The plasma clearance rates of 125I-LDL and 131I-cyclohexanedione-treated LDL were measured in four normal and four heterozygous familial hypercholesterolemic subjects. Chemical modification of the lipoprotein significantly reduced its fractional clearance rate and permitted calculation of receptor-mediated and receptor independent catabolism in both groups. The normal subjects cleared 11% of their plasma LDL pool (corresponding to 3.0 mg/kg per day) by a receptor-independent path. In tared daily by these pathways, respectively. Because the mean apoLDL pool size in the group was increased 3-fold over normal, this gave absolute clearance rates for the apoprotein of 2.5 mg/kg per day via the receptors and 12.8 mg/kg per day by the nonreceptor pathway. We conclude that the specific LDL receptor mechanism operates in vivo and probably accounts for 33% and 16% of overall LDL catabolism in normal and heterozygous familial hypercholesterolemic subjects, respectively.", "contents": "Receptor-mediated low density lipoprotein catabolism in man. Binding of human low density lipoproteins (LDL) to their specific receptor on cultured cells can be inhibited by treatment with 1,2-cyclohexanedione which blocks a number of functionally significant arginyl residues on the apolipoprotein. We have used this observation to examine the role of the receptor pathway in LDL catabolism in man. The plasma clearance rates of 125I-LDL and 131I-cyclohexanedione-treated LDL were measured in four normal and four heterozygous familial hypercholesterolemic subjects. Chemical modification of the lipoprotein significantly reduced its fractional clearance rate and permitted calculation of receptor-mediated and receptor independent catabolism in both groups. The normal subjects cleared 11% of their plasma LDL pool (corresponding to 3.0 mg/kg per day) by a receptor-independent path. In tared daily by these pathways, respectively. Because the mean apoLDL pool size in the group was increased 3-fold over normal, this gave absolute clearance rates for the apoprotein of 2.5 mg/kg per day via the receptors and 12.8 mg/kg per day by the nonreceptor pathway. We conclude that the specific LDL receptor mechanism operates in vivo and probably accounts for 33% and 16% of overall LDL catabolism in normal and heterozygous familial hypercholesterolemic subjects, respectively."}
{"id": "PMID:230270", "title": "Effects of lesions of the suprachiasmatic nuclei and of p-chlorophenylalanine on the circadian rhythms of adrenocorticotrophic hormone and corticosterone in the plasma, and on locomotor activity of rats.", "content": "Adrenocorticotrophin (ACTH) and corticosterone in the plasma of adult female rats were measured sequentially at 4 h intervals for 24 h before and after lesions of the suprachiasmatic nuclei or treatment with p-chlorophenylalanine (to inhibit serotonin synthesis). After lesions or p-chlorophenylalanine treatment, the concentrations of ACTH were diminished relative to those in control animals and rhythmic changes could not be detected. However, injection of animals, pretreated with p-chlorophenylalanine, with 5-hydroxytryptophan (60 mg/kg) 8 h before the time when plasma ACTH is maximal in intact animals, stimulated ACTH secretion up to control values. Mean corticosterone concentrations in plasma remained unchanged (after lesions) or increased (after p-chlorophenylalanine). This increase was associated with an increased minimal concentration of corticosterone. After both treatments there was evidence of continued circadian or ultradian rhythms of corticosterone concentration. Locomotor activity of female rats given identical treatment, but without blood sampling, indicated that nocturnal activity was diminished after lesions whereas diurnal activity was enhanced after p-chlorophenylalanine treatment. Periodicity analysis detected the persistence of free-running circadian, and sometimes ultradian activity, rhythms. Adrenalectomy did not alter further the activity pattern observed in rats with lesions. These results therefore support the proposition that both the suprachiasmatic nuclei and the serotoninergic system play an irreplaceable role in the mechanism of ACTH secretory rhythms. The suprachiasmatic nuclei are also important for synchronization of locomotor activity and corticosterone rhythms, which may both persist after the suppression of ACTH rhythms.", "contents": "Effects of lesions of the suprachiasmatic nuclei and of p-chlorophenylalanine on the circadian rhythms of adrenocorticotrophic hormone and corticosterone in the plasma, and on locomotor activity of rats. Adrenocorticotrophin (ACTH) and corticosterone in the plasma of adult female rats were measured sequentially at 4 h intervals for 24 h before and after lesions of the suprachiasmatic nuclei or treatment with p-chlorophenylalanine (to inhibit serotonin synthesis). After lesions or p-chlorophenylalanine treatment, the concentrations of ACTH were diminished relative to those in control animals and rhythmic changes could not be detected. However, injection of animals, pretreated with p-chlorophenylalanine, with 5-hydroxytryptophan (60 mg/kg) 8 h before the time when plasma ACTH is maximal in intact animals, stimulated ACTH secretion up to control values. Mean corticosterone concentrations in plasma remained unchanged (after lesions) or increased (after p-chlorophenylalanine). This increase was associated with an increased minimal concentration of corticosterone. After both treatments there was evidence of continued circadian or ultradian rhythms of corticosterone concentration. Locomotor activity of female rats given identical treatment, but without blood sampling, indicated that nocturnal activity was diminished after lesions whereas diurnal activity was enhanced after p-chlorophenylalanine treatment. Periodicity analysis detected the persistence of free-running circadian, and sometimes ultradian activity, rhythms. Adrenalectomy did not alter further the activity pattern observed in rats with lesions. These results therefore support the proposition that both the suprachiasmatic nuclei and the serotoninergic system play an irreplaceable role in the mechanism of ACTH secretory rhythms. The suprachiasmatic nuclei are also important for synchronization of locomotor activity and corticosterone rhythms, which may both persist after the suppression of ACTH rhythms."}
{"id": "PMID:230279", "title": "Prolactin receptors in the mammary gland, corpus luteum and other tissues of the tammar wallaby, Macropus eugenii.", "content": "Specific binding of radio-iodinated ovine prolactin to subcellular tissue fractions of the tammar wallaby (Macropus eugenii) was investigated. Specific binding was found, in order of decreasing binding activity, in the lactating mammary gland, corpus luteum, corpus albicans, adrenal gland and ovary. Specific binding was absent in kidney, liver, brain and inactive mammary gland. The mean association constant (Ka at 23 degrees C) was determined as 0.90 x 10(9), 2.20 x 10(9), 2.44 x 10(9), 3.38 x 10(9) and 10.98 x 10(9) l/mol for mammary gland, adrenal, corpus albicans, corpus luteum and ovary respectively. The mean receptor concentration (N) varied from 92.87 x 10(-14) mol/mg protein for the mammary gland to 1.03 x 10(-14) mol/mg protein for the ovary. The concentration in the corpus luteum varied between tissue pools collected at different times of the annual breeding cycle. The specificity for prolactin was shown in the mammary gland and corpus luteum by the failure of ovine FSH, LH, GH and TSH to displace 125I-labelled ovine prolactin, whereas it was displaced readily by both ovine and bovine prolactin.", "contents": "Prolactin receptors in the mammary gland, corpus luteum and other tissues of the tammar wallaby, Macropus eugenii. Specific binding of radio-iodinated ovine prolactin to subcellular tissue fractions of the tammar wallaby (Macropus eugenii) was investigated. Specific binding was found, in order of decreasing binding activity, in the lactating mammary gland, corpus luteum, corpus albicans, adrenal gland and ovary. Specific binding was absent in kidney, liver, brain and inactive mammary gland. The mean association constant (Ka at 23 degrees C) was determined as 0.90 x 10(9), 2.20 x 10(9), 2.44 x 10(9), 3.38 x 10(9) and 10.98 x 10(9) l/mol for mammary gland, adrenal, corpus albicans, corpus luteum and ovary respectively. The mean receptor concentration (N) varied from 92.87 x 10(-14) mol/mg protein for the mammary gland to 1.03 x 10(-14) mol/mg protein for the ovary. The concentration in the corpus luteum varied between tissue pools collected at different times of the annual breeding cycle. The specificity for prolactin was shown in the mammary gland and corpus luteum by the failure of ovine FSH, LH, GH and TSH to displace 125I-labelled ovine prolactin, whereas it was displaced readily by both ovine and bovine prolactin."}
{"id": "PMID:230280", "title": "In vivo and in vitro studies on the early embryonic lethal oligosyndactylism (Os) in the mouse.", "content": "The development of mouse embryos homozygous for oligosyndactylism (Os) is arrested during implantation. Histological investigations confirm a previous report that cells become blocked in mitosis, and air-dried spreads of the mutant embryos reveal that large numbers of cells accumulate in metaphase. Trophoblastic giant cells appear unaffected by the action of the mutant gene both in utero and during culture over the lethal phase. It is proposed that the form of endoreduplication undergone by giant cells renders them refractory to the metaphase block.", "contents": "In vivo and in vitro studies on the early embryonic lethal oligosyndactylism (Os) in the mouse. The development of mouse embryos homozygous for oligosyndactylism (Os) is arrested during implantation. Histological investigations confirm a previous report that cells become blocked in mitosis, and air-dried spreads of the mutant embryos reveal that large numbers of cells accumulate in metaphase. Trophoblastic giant cells appear unaffected by the action of the mutant gene both in utero and during culture over the lethal phase. It is proposed that the form of endoreduplication undergone by giant cells renders them refractory to the metaphase block."}
{"id": "PMID:230281", "title": "Gene expression in Dictyostelium discoidium: mutually antagonistic roles of cyclic-AMP and ammonia.", "content": "Cyclic-AMP and ammonia have been previously identified as extracellular signals during Dictyostelium development. Both are important in controlling morphological movements and cyclic-AMP also in inducing gene expression. The work in tis paper is concerned with their effects on developmental gene expression. Cyclic-AMP was found to act as an inducer during the aggregative (as exemplified by phosphodiesterase) and the post-aggregative (glycogen phosphorylase, UDP-galactose polysaccharide transferase, prespore vacuoles and stalk cells) phases of gene expression. Ammonia inhibited the appearance of each of the above markers and antagonized the inductive effects of cyclic-AMP on them. This inhibition by ammonia of cyclic-AMP inducible gene expression may involve a step linking elevated intracellular cyclic-AMP levels to gene activation. It has been suggested that the specification of cells within the aggregate into the stalk and spore pathways of differentiation might be controlled by cyclic-AMP and ammonia. In this model for pattern formation cyclic-AMP would induce stalk cell differentiation and ammonia spore formation. The present results argue against this idea since cyclic-AMP induces and ammonia inhibits differentiation along both pathways. The function of these agents may rather be to coordinate the rates of biochemical differentiation of individual cells and link them to the overall morphological changes occurring during development.", "contents": "Gene expression in Dictyostelium discoidium: mutually antagonistic roles of cyclic-AMP and ammonia. Cyclic-AMP and ammonia have been previously identified as extracellular signals during Dictyostelium development. Both are important in controlling morphological movements and cyclic-AMP also in inducing gene expression. The work in tis paper is concerned with their effects on developmental gene expression. Cyclic-AMP was found to act as an inducer during the aggregative (as exemplified by phosphodiesterase) and the post-aggregative (glycogen phosphorylase, UDP-galactose polysaccharide transferase, prespore vacuoles and stalk cells) phases of gene expression. Ammonia inhibited the appearance of each of the above markers and antagonized the inductive effects of cyclic-AMP on them. This inhibition by ammonia of cyclic-AMP inducible gene expression may involve a step linking elevated intracellular cyclic-AMP levels to gene activation. It has been suggested that the specification of cells within the aggregate into the stalk and spore pathways of differentiation might be controlled by cyclic-AMP and ammonia. In this model for pattern formation cyclic-AMP would induce stalk cell differentiation and ammonia spore formation. The present results argue against this idea since cyclic-AMP induces and ammonia inhibits differentiation along both pathways. The function of these agents may rather be to coordinate the rates of biochemical differentiation of individual cells and link them to the overall morphological changes occurring during development."}
{"id": "PMID:230283", "title": "Induction of simian virus 40-specific tumour rejection by the Ad2+ND2 hybrid virus.", "content": "Immunization of BALB/c mice with Ad2+ND2, a non-defective hybrid virus containing about half of the early region of simian virus 40 (SV40) DNA covalently integrated into the human adenovirus 2 (Ad2) genome, can confer protection against subsequent challenge by syngeneic SV40 tumour cells. Analysis of subcellular fractions from Ad2+ND2-infected cells shows a close correlation between the tumour rejection activity and the presence of the two SV40-specific proteins induced by this hybrid virus. These two proteins, with mol. wt. of 56 000 (56K) and 42 000 (42K), can be specifically immunoprecipitated using sera obtained from hamsters bearing SV40-induced tumours. Such immunoprecipitates, which contain no detectable contaminating components as determined by polyacrylamide gel electrophoresis, can efficiently immunize mice against SV40 tumour challenge, suggesting that the 56K and 42K proteins are directly responsible for the induction of tumour rejection. Moreover, we have found, by immunoprecipitation, a novel antigen in SV40-transformed BALB/c cells, also of 56 000 mol. wt.; possibly, this 56K protein is responsible for induction of transplantation immunity in SV40-transformed cells.", "contents": "Induction of simian virus 40-specific tumour rejection by the Ad2+ND2 hybrid virus. Immunization of BALB/c mice with Ad2+ND2, a non-defective hybrid virus containing about half of the early region of simian virus 40 (SV40) DNA covalently integrated into the human adenovirus 2 (Ad2) genome, can confer protection against subsequent challenge by syngeneic SV40 tumour cells. Analysis of subcellular fractions from Ad2+ND2-infected cells shows a close correlation between the tumour rejection activity and the presence of the two SV40-specific proteins induced by this hybrid virus. These two proteins, with mol. wt. of 56 000 (56K) and 42 000 (42K), can be specifically immunoprecipitated using sera obtained from hamsters bearing SV40-induced tumours. Such immunoprecipitates, which contain no detectable contaminating components as determined by polyacrylamide gel electrophoresis, can efficiently immunize mice against SV40 tumour challenge, suggesting that the 56K and 42K proteins are directly responsible for the induction of tumour rejection. Moreover, we have found, by immunoprecipitation, a novel antigen in SV40-transformed BALB/c cells, also of 56 000 mol. wt.; possibly, this 56K protein is responsible for induction of transplantation immunity in SV40-transformed cells."}
{"id": "PMID:230284", "title": "Modulation of herpes simplex virus replication in adenovirus transformed cells.", "content": "The ability of herpes simplex virus 1 to replicate in cells transformed by adenovirus type 5 is strongly dependent on the origin of the cells. Studies show that adenovirus transformed rat cells lose their permissiveness while cells of hamster or human origin retain their ability to replicate HSV although at a reduced level when compared to the untransformed parent cells. One line of adenovirus transformed rat cells, 107, demonstrates thermosensitive events, allowing HSV to replicate at 34 degrees C but not at 37 degrees C. Analysis of the biochemical events taking place at 37 degrees C showed that virus-specific DNA synthesis was greatly reduced but that all of the late virus structural proteins could be observed after SDS-polyacrylamide gel electrophoresis. It was also demonstrated that shut-off of host macromolecular synthesis appeared to be less efficient after HSV infection of 107 cells than after infection of more permissive cells such as the non-transformed REF line. Collectively the data show that interactions between HSV and the host cell are perturbed when the cell is transformed by type 5 adenovirus. The degree of perturbation ranges from a slight reduction in number of progeny to a completely abortive infection.", "contents": "Modulation of herpes simplex virus replication in adenovirus transformed cells. The ability of herpes simplex virus 1 to replicate in cells transformed by adenovirus type 5 is strongly dependent on the origin of the cells. Studies show that adenovirus transformed rat cells lose their permissiveness while cells of hamster or human origin retain their ability to replicate HSV although at a reduced level when compared to the untransformed parent cells. One line of adenovirus transformed rat cells, 107, demonstrates thermosensitive events, allowing HSV to replicate at 34 degrees C but not at 37 degrees C. Analysis of the biochemical events taking place at 37 degrees C showed that virus-specific DNA synthesis was greatly reduced but that all of the late virus structural proteins could be observed after SDS-polyacrylamide gel electrophoresis. It was also demonstrated that shut-off of host macromolecular synthesis appeared to be less efficient after HSV infection of 107 cells than after infection of more permissive cells such as the non-transformed REF line. Collectively the data show that interactions between HSV and the host cell are perturbed when the cell is transformed by type 5 adenovirus. The degree of perturbation ranges from a slight reduction in number of progeny to a completely abortive infection."}
{"id": "PMID:230285", "title": "Sequence studies of poliovirus RNA. IV. Nucleotide sequence complexities of poliovirus type 1, type 2 and two type 1 defective interfering particles RNAs, and fingerprint of the poliovirus type 3 genome.", "content": "The 32P-labelled genomes of poliovirus type 1, 2 and 3 have been digested with RNase T1 and the products separated by two-dimensional gel electrophoresis. All three fingerprints differ in the separation pattern of the large oligonucleotides. The molar yields of the large RNase T1-resistant oligonucleotides of type 1 and type 2 RNA of poliovirus RNA are close to one. By comparing the yields of these oligonucleotides to the amount of RNA from which they originated, the chain length of type 1 poliovirus RNA was found to be 7851 +/- 567 nucleotides (mol. wt. 2.66 +/- 0.19 x 10(6) and that of poliovirus type 2, 8181 +/- 578 nucleotides (mol. wt. 2.77 +/- 0.19 x 10(6). The chain length of two defective interfering particle (DI) RNAs of poliovirus type 1 were determined to be 7042 +/- 999 nucleotides for DI(1) and 6639 +/- 674 nucleotides for DI(2).", "contents": "Sequence studies of poliovirus RNA. IV. Nucleotide sequence complexities of poliovirus type 1, type 2 and two type 1 defective interfering particles RNAs, and fingerprint of the poliovirus type 3 genome. The 32P-labelled genomes of poliovirus type 1, 2 and 3 have been digested with RNase T1 and the products separated by two-dimensional gel electrophoresis. All three fingerprints differ in the separation pattern of the large oligonucleotides. The molar yields of the large RNase T1-resistant oligonucleotides of type 1 and type 2 RNA of poliovirus RNA are close to one. By comparing the yields of these oligonucleotides to the amount of RNA from which they originated, the chain length of type 1 poliovirus RNA was found to be 7851 +/- 567 nucleotides (mol. wt. 2.66 +/- 0.19 x 10(6) and that of poliovirus type 2, 8181 +/- 578 nucleotides (mol. wt. 2.77 +/- 0.19 x 10(6). The chain length of two defective interfering particle (DI) RNAs of poliovirus type 1 were determined to be 7042 +/- 999 nucleotides for DI(1) and 6639 +/- 674 nucleotides for DI(2)."}
{"id": "PMID:230286", "title": "Studies of the effect of chloramphenicol, ethidium bromide and camptothecin on the reproduction of Rous sarcoma virus in infected chick embryo cells.", "content": "A function for mitochondria in the reproduction of Rous sarcoma virus (RSV) in chronically and newly infected chick embryo cells was studied by using chloramphenicol and ethidium bromide. Chloramphenicol (CAM) and ethidium bromide (EB) were both shown to decrease the rate of growth of infected chick embryo cells and to inhibit the synthesis of mitochondrial macromolecules. Both drugs however had little or no effect on the incorporation of labelled leucine, thymidine and uridine into total cellular macromolecules. Neither CAM (80 microgram/ml) nor EB (0.4 microgram/ml) inhibited the production of infectious virus. In contrast, camptothecin, an inhibitor of cellular but not mitochondrial macromolecular synthesis, was shown to depress the production of infectious virus. The results indicate that the mitochondrial macromolecular synthesis machinery of RSV-infected chick embryo cells does not contribute to virus production.", "contents": "Studies of the effect of chloramphenicol, ethidium bromide and camptothecin on the reproduction of Rous sarcoma virus in infected chick embryo cells. A function for mitochondria in the reproduction of Rous sarcoma virus (RSV) in chronically and newly infected chick embryo cells was studied by using chloramphenicol and ethidium bromide. Chloramphenicol (CAM) and ethidium bromide (EB) were both shown to decrease the rate of growth of infected chick embryo cells and to inhibit the synthesis of mitochondrial macromolecules. Both drugs however had little or no effect on the incorporation of labelled leucine, thymidine and uridine into total cellular macromolecules. Neither CAM (80 microgram/ml) nor EB (0.4 microgram/ml) inhibited the production of infectious virus. In contrast, camptothecin, an inhibitor of cellular but not mitochondrial macromolecular synthesis, was shown to depress the production of infectious virus. The results indicate that the mitochondrial macromolecular synthesis machinery of RSV-infected chick embryo cells does not contribute to virus production."}
{"id": "PMID:230287", "title": "Pathogenesis of murine cytomegalovirus infection: the macrophage as a permissive cell for cytomegalovirus infection, replication and latency.", "content": "Macrophages harvested from the peritoneal cavities of mice of several strains were permissive to infection with murine cytomegalovirus (MCMV). Macrophages from six mouse strains released equivalent amounts of plaque-forming virus into the culture fluids and cells from mouse strains scored similarly in numbers of infectious centres. Twenty to 50% of the infected macrophages obtained after thioglycollate activation formed infectious centres. When studied by in situ hybridization, more than 82% of infected macrophages (with or without thioglycollate activation) contained MCMV DNA. Macrophages obtained from latently infected mice were examined for their content of MCMV. Using co-cultivation assays, MCMV was frequently recovered from thioglycollate activated macrophages harvested from latently infected mice but only rarely recovered from non-activated macrophages. MCMV DNA--mouse DNA hybridization assays revealed four to seven virus genome DNA copies per 100 cells. These studies indicate that macrophages harvested from mice susceptible (BALB/cSt) or resistant (C3H) to MCMV infection replicated virus equivalently and that macrophages are a reservoir of MCMV during latent and chronic infections. Activation of macrophages may be one of the important steps leading to the exacerbation of in vivo latent infections.", "contents": "Pathogenesis of murine cytomegalovirus infection: the macrophage as a permissive cell for cytomegalovirus infection, replication and latency. Macrophages harvested from the peritoneal cavities of mice of several strains were permissive to infection with murine cytomegalovirus (MCMV). Macrophages from six mouse strains released equivalent amounts of plaque-forming virus into the culture fluids and cells from mouse strains scored similarly in numbers of infectious centres. Twenty to 50% of the infected macrophages obtained after thioglycollate activation formed infectious centres. When studied by in situ hybridization, more than 82% of infected macrophages (with or without thioglycollate activation) contained MCMV DNA. Macrophages obtained from latently infected mice were examined for their content of MCMV. Using co-cultivation assays, MCMV was frequently recovered from thioglycollate activated macrophages harvested from latently infected mice but only rarely recovered from non-activated macrophages. MCMV DNA--mouse DNA hybridization assays revealed four to seven virus genome DNA copies per 100 cells. These studies indicate that macrophages harvested from mice susceptible (BALB/cSt) or resistant (C3H) to MCMV infection replicated virus equivalently and that macrophages are a reservoir of MCMV during latent and chronic infections. Activation of macrophages may be one of the important steps leading to the exacerbation of in vivo latent infections."}
{"id": "PMID:230288", "title": "Studies on the induction of IgG-Fc receptors and synthesis of IgM in primary and chronically-infected lymphoid (Raji) cells by herpes simplex virus.", "content": "The present paper reports on the induction of two cell surface markers on human lymphoid cells following herpes simplex virus (HSV) infection. While both primary and chronic infections of human lymphoid cells led to the induction of receptors for the Fc region of 7S IgG, chronic HSV infection was also characterized by the induction of surface-bound IgM. Surface and intracellular Fc receptors were detected in the human lymphoid cell line, Raji, infected with HSV types 1 and 2. Under optimal conditions with a multiplicity of infection (m.o.i.) of 50 to 100 p.f.u. per cell, this marker was inducible in only about 53% of the infected cells. Kinetic studies revealed the appearance of these receptors at around 5 h following HSV infection and they reached a plateau 16 to 18 h p.i. Interestingly, this Fc receptor expression (i.e. percentage of positive cells) was found to be similar in primary and chronically HSV-infected Raji cells. Both human leukocyte interferon and phosphonoacetic acid (PAA), an inhibitor of herpesvirus DNA polymerase activity, effectively inhibited Fc receptor synthesis during primary HSV-infection and these two agents suppressed its induction in chronically HSV-infected Raji (Raji-HSV) cells. This inhibitory or suppressive effect, particularly of PAA, suggests that this HSV-induced Fc receptor may represent a late virus function in the infected cell. Unlike primary HSV infection, about 80% of the chronically HSV-infected Raji cells were found to express surface-bound IgM. This IgM induction was suppressed by long-term interferon treatment but not with PAA-treatment. Superinfection studies of interferon and PAA-treated Raji-HSV cells indicate that only the former would develop Fc receptors suggesting a protective role of this IgM against superinfection by HSV.", "contents": "Studies on the induction of IgG-Fc receptors and synthesis of IgM in primary and chronically-infected lymphoid (Raji) cells by herpes simplex virus. The present paper reports on the induction of two cell surface markers on human lymphoid cells following herpes simplex virus (HSV) infection. While both primary and chronic infections of human lymphoid cells led to the induction of receptors for the Fc region of 7S IgG, chronic HSV infection was also characterized by the induction of surface-bound IgM. Surface and intracellular Fc receptors were detected in the human lymphoid cell line, Raji, infected with HSV types 1 and 2. Under optimal conditions with a multiplicity of infection (m.o.i.) of 50 to 100 p.f.u. per cell, this marker was inducible in only about 53% of the infected cells. Kinetic studies revealed the appearance of these receptors at around 5 h following HSV infection and they reached a plateau 16 to 18 h p.i. Interestingly, this Fc receptor expression (i.e. percentage of positive cells) was found to be similar in primary and chronically HSV-infected Raji cells. Both human leukocyte interferon and phosphonoacetic acid (PAA), an inhibitor of herpesvirus DNA polymerase activity, effectively inhibited Fc receptor synthesis during primary HSV-infection and these two agents suppressed its induction in chronically HSV-infected Raji (Raji-HSV) cells. This inhibitory or suppressive effect, particularly of PAA, suggests that this HSV-induced Fc receptor may represent a late virus function in the infected cell. Unlike primary HSV infection, about 80% of the chronically HSV-infected Raji cells were found to express surface-bound IgM. This IgM induction was suppressed by long-term interferon treatment but not with PAA-treatment. Superinfection studies of interferon and PAA-treated Raji-HSV cells indicate that only the former would develop Fc receptors suggesting a protective role of this IgM against superinfection by HSV."}
{"id": "PMID:230290", "title": "The isolation of Mengo virus stable non-capsid polypeptides from infected L cells and preliminary characterization of an RNA polymerase activity associated with polypeptide E.", "content": "Isolation of the Mengo virus stable non-capsid virus polypeptides E, F, G and I from infected L cells has been achieved. Unstable precursors were eliminated by incubation in the presence of pactamycin and capsid polypeptides were removed by ultracentrifugation and affinity chromatography. Subsequent sodium dodecyl sulphate (SDS)-hydroxylapatite chromatography resolved the non-capsid proteins into two major peaks which comprised F plus G and E plus I, respectively. The individual polypeptide species were separated by gel filtration on Sephadex G-100 in the presence of SDS. Polypeptide E was isolated in an undenatured form by gel filtration of infected cell extracts (from which precursor and capsid polypeptides had been removed) on Bio-Gel A-5m agarose beads. Purified polypeptide E was found to co-sediment with Mengo virion RNA during centrifugation in a sucrose density gradient and it was also capable of binding to poly(A)-Sepharose. Assay mixtures containing polypeptide E exhibited an RNA polymerase activity which was dependent upon exogenous virus RNA template and oligo(U) primer and which was not affected by the addition of virus capsid polypeptides or extracts from uninfected cells.", "contents": "The isolation of Mengo virus stable non-capsid polypeptides from infected L cells and preliminary characterization of an RNA polymerase activity associated with polypeptide E. Isolation of the Mengo virus stable non-capsid virus polypeptides E, F, G and I from infected L cells has been achieved. Unstable precursors were eliminated by incubation in the presence of pactamycin and capsid polypeptides were removed by ultracentrifugation and affinity chromatography. Subsequent sodium dodecyl sulphate (SDS)-hydroxylapatite chromatography resolved the non-capsid proteins into two major peaks which comprised F plus G and E plus I, respectively. The individual polypeptide species were separated by gel filtration on Sephadex G-100 in the presence of SDS. Polypeptide E was isolated in an undenatured form by gel filtration of infected cell extracts (from which precursor and capsid polypeptides had been removed) on Bio-Gel A-5m agarose beads. Purified polypeptide E was found to co-sediment with Mengo virion RNA during centrifugation in a sucrose density gradient and it was also capable of binding to poly(A)-Sepharose. Assay mixtures containing polypeptide E exhibited an RNA polymerase activity which was dependent upon exogenous virus RNA template and oligo(U) primer and which was not affected by the addition of virus capsid polypeptides or extracts from uninfected cells."}
{"id": "PMID:230291", "title": "Morphogenesis of nuclear inclusions and virus capsids in HEL cells infected with temperature-sensitive mutants of human cytomegalovirus.", "content": "The morphogenesis of nuclear inclusions and virus capsids in human embryonic lung cells infected with ts mutants of human cytomegalovirus at permissive (34 degrees C) and non-permissive (39 degrees C) temperatures was studied by indirect immunofluorescence (IF) and electron microscopic analyses and compared with the morphogenesis of these structures in wild-type virus infection with or without phosphonoacetate. Mutants tested belonged to five different complementation groups: two groups were DNA- (those unable to synthesize virus DNA at 39 degrees C) and the others were dna+. Based on the previous finding that the electron-dense, reticular nuclear inclusions (EM-NI) observed by the thin-section analysis correspond with nuclear inclusions (IF-NI) detected by the indirect IF staining (i.e. they occupy the same space in the nucleus), the following conclusions were obtained in ts mutant infection at 39 degrees C: (i) the formation of EM-NI, IF-NI and virus capsids requires replication of virus DNA. (II) The formation of EM-NI is not necessarily accompanied by the formation of IF-NI; EM-NI itself is not IF-positive unless it acquires virus-specific late antigens. (iii) The assembly of virus capsids occurs only in those cells in which EM-NI is formed; however, it can occur without the formation of IF-NI. (iv) Virus capsids assembled are not the major antigens responsible for the fluorescence of nuclear inclusions.", "contents": "Morphogenesis of nuclear inclusions and virus capsids in HEL cells infected with temperature-sensitive mutants of human cytomegalovirus. The morphogenesis of nuclear inclusions and virus capsids in human embryonic lung cells infected with ts mutants of human cytomegalovirus at permissive (34 degrees C) and non-permissive (39 degrees C) temperatures was studied by indirect immunofluorescence (IF) and electron microscopic analyses and compared with the morphogenesis of these structures in wild-type virus infection with or without phosphonoacetate. Mutants tested belonged to five different complementation groups: two groups were DNA- (those unable to synthesize virus DNA at 39 degrees C) and the others were dna+. Based on the previous finding that the electron-dense, reticular nuclear inclusions (EM-NI) observed by the thin-section analysis correspond with nuclear inclusions (IF-NI) detected by the indirect IF staining (i.e. they occupy the same space in the nucleus), the following conclusions were obtained in ts mutant infection at 39 degrees C: (i) the formation of EM-NI, IF-NI and virus capsids requires replication of virus DNA. (II) The formation of EM-NI is not necessarily accompanied by the formation of IF-NI; EM-NI itself is not IF-positive unless it acquires virus-specific late antigens. (iii) The assembly of virus capsids occurs only in those cells in which EM-NI is formed; however, it can occur without the formation of IF-NI. (iv) Virus capsids assembled are not the major antigens responsible for the fluorescence of nuclear inclusions."}
{"id": "PMID:230292", "title": "Differences in the morphology of herpes simplex virus infected cells: I. Comparative scanning and transmission electron microscopic studies on HSV-1 infected HEp-2 and chick embryo fibroblast cells.", "content": "Infection with herpes simplex virus type 1 (HSV-1) induces different morphological changes in different cell lines. This is demonstrated by comparative scanning (SEM and transmission (TEM) electron microscopic investigations of cell cultures prepared under identical conditions. SEM of HSV-1 infected HEp-2 cells reveals a slightly altered cell surface: only the number of the microvilli is reduced. Large amounts of released virions are detectable adhering to the outer plasma membrane. Ultra-thin sections show typical virus maturation steps in the nuclei (formation of nucleocapsids and virus budding from the inner lamella of the nuclear membrane) and in the cytoplasm (egress of enveloped nucleocapsids through membranous structures). HSV-infected primary chick embryo fibroblast (CEF) cells are characterized by crumpled and rough surfaces without virus particles adhering to the membrane. Ultra-thin sections exhibit atypical virus maturation with many unenveloped nucleocapsids within the cytoplasm. The distribution of HSV-induced antigen(s) on the surface of the infected cells is identical in the two cell systems as determined by the peroxidase labelling technique. The c.p.e. (as seen by phase contrast light microscopy) is similar in both HEp-2 and CEF cells: both fusion and rounding up is induced in the infected cells.", "contents": "Differences in the morphology of herpes simplex virus infected cells: I. Comparative scanning and transmission electron microscopic studies on HSV-1 infected HEp-2 and chick embryo fibroblast cells. Infection with herpes simplex virus type 1 (HSV-1) induces different morphological changes in different cell lines. This is demonstrated by comparative scanning (SEM and transmission (TEM) electron microscopic investigations of cell cultures prepared under identical conditions. SEM of HSV-1 infected HEp-2 cells reveals a slightly altered cell surface: only the number of the microvilli is reduced. Large amounts of released virions are detectable adhering to the outer plasma membrane. Ultra-thin sections show typical virus maturation steps in the nuclei (formation of nucleocapsids and virus budding from the inner lamella of the nuclear membrane) and in the cytoplasm (egress of enveloped nucleocapsids through membranous structures). HSV-infected primary chick embryo fibroblast (CEF) cells are characterized by crumpled and rough surfaces without virus particles adhering to the membrane. Ultra-thin sections exhibit atypical virus maturation with many unenveloped nucleocapsids within the cytoplasm. The distribution of HSV-induced antigen(s) on the surface of the infected cells is identical in the two cell systems as determined by the peroxidase labelling technique. The c.p.e. (as seen by phase contrast light microscopy) is similar in both HEp-2 and CEF cells: both fusion and rounding up is induced in the infected cells."}
{"id": "PMID:230293", "title": "Establishment of persistent infection by parainfluenza virus type 3: role of a syncytium inhibitor.", "content": "A strain of parainfluenza virus type 3 (para 3) that had undergone a series of undiluted passages failed to produce syncytia when inoculated on to Vero cells at a high m.o.i. The strain repeatedly produced stable persistent infections. Persistently infected cells were resistant to superinfection by homologous virus, showed the presence of virus-specific antigen and shed low quantities of infectious virus into the supernatant fluid. The undiluted passage parainfluenza virus type 3 strain produced a substance that inhibited syncytium formation by homologous virus and by measles virus but appeared to have no effect on virus replication. This inhibitor had no demonstrable effect on unrelated viruses, including some that produced syncytia. It had a mol. wt. between 3500 and 14000, was acid- and heat-labile, and was inactivated by anti-para 3 serum.", "contents": "Establishment of persistent infection by parainfluenza virus type 3: role of a syncytium inhibitor. A strain of parainfluenza virus type 3 (para 3) that had undergone a series of undiluted passages failed to produce syncytia when inoculated on to Vero cells at a high m.o.i. The strain repeatedly produced stable persistent infections. Persistently infected cells were resistant to superinfection by homologous virus, showed the presence of virus-specific antigen and shed low quantities of infectious virus into the supernatant fluid. The undiluted passage parainfluenza virus type 3 strain produced a substance that inhibited syncytium formation by homologous virus and by measles virus but appeared to have no effect on virus replication. This inhibitor had no demonstrable effect on unrelated viruses, including some that produced syncytia. It had a mol. wt. between 3500 and 14000, was acid- and heat-labile, and was inactivated by anti-para 3 serum."}
{"id": "PMID:230294", "title": "Topographical studies on poliovirus capsid proteins by chemical modification and cross-linking with bifunctional reagents.", "content": "Poliovirus capsid proteins comprise 15.1 lysines in VP1, 5.6 lysines in VP2, 11.7 lysines in VP3 and 5.5 lysines in VP4. Treatment with monofunctional reagent N-succinimidyl 2,3-3H-proprionate leads to the modification of 3.4 lysines in VP1, 0.6 lysines in VP2, 2.0 lysines in VP3 and 0.03 lysines in VP4. Chemical modification with the monofunctional reagent N-succinimidyl 3-(4-hydroxy,5-125I-iodophenyl)propionate results in a predominant labelling of VP1 and VP3, whereas VP2 is less accessible and VP4 is not modified. Cross-linking of poliovirus with bifunctional imidoesters, dimethyl suberimidate (DMS, 1.1 nm) and dimethyl adipimidate (DMA, 0.8 nm) leads to a new protein complex of mol. wt. which corresponds to the sum of VP1 and VP3. By cleavage with ammonia and electrophoresis on polyacrylamide gels in SDS, the proteins are identified as VP1 and VP3. This result gives evidence for a direct neighbourhood of VP1 and VP3 in the virus capsid. Treatment of the virus with the mono- and bifunctional reagents has no influence on the stability of the particle. The infectivity is reduced only by the bifunctional reagent.", "contents": "Topographical studies on poliovirus capsid proteins by chemical modification and cross-linking with bifunctional reagents. Poliovirus capsid proteins comprise 15.1 lysines in VP1, 5.6 lysines in VP2, 11.7 lysines in VP3 and 5.5 lysines in VP4. Treatment with monofunctional reagent N-succinimidyl 2,3-3H-proprionate leads to the modification of 3.4 lysines in VP1, 0.6 lysines in VP2, 2.0 lysines in VP3 and 0.03 lysines in VP4. Chemical modification with the monofunctional reagent N-succinimidyl 3-(4-hydroxy,5-125I-iodophenyl)propionate results in a predominant labelling of VP1 and VP3, whereas VP2 is less accessible and VP4 is not modified. Cross-linking of poliovirus with bifunctional imidoesters, dimethyl suberimidate (DMS, 1.1 nm) and dimethyl adipimidate (DMA, 0.8 nm) leads to a new protein complex of mol. wt. which corresponds to the sum of VP1 and VP3. By cleavage with ammonia and electrophoresis on polyacrylamide gels in SDS, the proteins are identified as VP1 and VP3. This result gives evidence for a direct neighbourhood of VP1 and VP3 in the virus capsid. Treatment of the virus with the mono- and bifunctional reagents has no influence on the stability of the particle. The infectivity is reduced only by the bifunctional reagent."}
{"id": "PMID:230295", "title": "Latent cytomegalovirus infection of BALB/c mouse spleens detected by an explant culture technique.", "content": "Latent murine cytomegalovirus (MCMV) infection of BALB/c mouse spleens was studied using several methods including an explant tissue culture technique, co-cultivation on allogeneic and syngeneic cell cultures and nucleic acid hybridization. BALB/c mice experience latent infection which persists for at least 6 months and involves only a small fraction of spleen cells. The explant culture technique proved to be much more sensitive than other methods for detecting latent infection of lymphoid tissues.", "contents": "Latent cytomegalovirus infection of BALB/c mouse spleens detected by an explant culture technique. Latent murine cytomegalovirus (MCMV) infection of BALB/c mouse spleens was studied using several methods including an explant tissue culture technique, co-cultivation on allogeneic and syngeneic cell cultures and nucleic acid hybridization. BALB/c mice experience latent infection which persists for at least 6 months and involves only a small fraction of spleen cells. The explant culture technique proved to be much more sensitive than other methods for detecting latent infection of lymphoid tissues."}
{"id": "PMID:230296", "title": "Serologically cross-reactive polypeptides in vaccinia, cowpox and Shope fibroma viruses.", "content": "An immunoprecipitation method coupled with SDS-polyacrylamide gel electrophoresis (SDS-PAGE) was used to identify the serologically cross-reactive polypeptides in Orthopoxvirus (vaccinia and cowpox viruses) and Leporipoxvirus (Shope fibroma virus). Two early and four late polypeptides in cells infected with vaccinia or cowpox virus were specifically immunoprecipitated with antiserum against Shope fibroma virus. Two early and two late polypeptides in cells infected with Shope fibroma virus cross-reacted with both antiserum against vaccinia virus and antiserum against cowpox virus. The possibility of the common polypeptides being related to nucleoprotein antigen in these cross-reactive polypeptides was discussed.", "contents": "Serologically cross-reactive polypeptides in vaccinia, cowpox and Shope fibroma viruses. An immunoprecipitation method coupled with SDS-polyacrylamide gel electrophoresis (SDS-PAGE) was used to identify the serologically cross-reactive polypeptides in Orthopoxvirus (vaccinia and cowpox viruses) and Leporipoxvirus (Shope fibroma virus). Two early and four late polypeptides in cells infected with vaccinia or cowpox virus were specifically immunoprecipitated with antiserum against Shope fibroma virus. Two early and two late polypeptides in cells infected with Shope fibroma virus cross-reacted with both antiserum against vaccinia virus and antiserum against cowpox virus. The possibility of the common polypeptides being related to nucleoprotein antigen in these cross-reactive polypeptides was discussed."}
{"id": "PMID:230297", "title": "Mode of integration of Epstein-Barr virus genome into host DNA in Burkitt lymphoma cells.", "content": "The ebv dna integrated into the host genome from cell of an African Burkitt lymphoma biopsy has been compared to the corresponding fraction of EBV DNA from the cell line SU-AmB-2 which is of American Burkitt lymphoma origin. It is shown that while, in the case of the African biopsy, large pieces of EBV DNA sequences are integrated into the host DNA, much smaller pieces of virus DNA are integrated into the DNA of the SU-AmB-2 cells. The possibility that this difference might be related to the fact that EBV is rarely associated with Burkitt lymphomas outside East Africa is discussed.", "contents": "Mode of integration of Epstein-Barr virus genome into host DNA in Burkitt lymphoma cells. The ebv dna integrated into the host genome from cell of an African Burkitt lymphoma biopsy has been compared to the corresponding fraction of EBV DNA from the cell line SU-AmB-2 which is of American Burkitt lymphoma origin. It is shown that while, in the case of the African biopsy, large pieces of EBV DNA sequences are integrated into the host DNA, much smaller pieces of virus DNA are integrated into the DNA of the SU-AmB-2 cells. The possibility that this difference might be related to the fact that EBV is rarely associated with Burkitt lymphomas outside East Africa is discussed."}
{"id": "PMID:230298", "title": "Possible point mutation sites in LSc, 2ab poliovirus RNA and a protein covalently linked to the 5'-terminus.", "content": "Poliovirus type I, vaccine strain (LSc, 2ab), which is a temperature- and actinomycin D-sensitive mutant derived from type I Mahoney strain, was grown in HeLa cells in the presence of 32P and a low concentration of actinomycin D. Seven and a half h p.i., genome 32P-RNA was recovered from the purified virion. Analysis of RNase TI digests of the RNA by two-dimensional gel electrophoresis revealed that three possible point mutation sites exist in the large and unique oligonucleotides in the fingerprint. Neither a capping structure nor a nucleotide such as pppNp, ppNp or pNp, was detected by ion exchange column chromatography at pH 5.0 after digestion of virion RNA with RNase T2. Instead, a 32P-labelled compound, which could be digested with Pronase or proteinase K, was eluted at the void volume of the column. Proteinase K digests of the 32P-labelled compound contained pUp or pU as a single labelled c\"mpound, when genome RNA was digested with RNase T2 or nuclease P1, respectively, before digestion with the proteinase. Our data locate possible point mutation sites on the genome of a mutant strain (LSc, 2ab) of type I poliovirus and show that a protein (VPg) is covalently bound to the 5'-terminus of RNA. The protein (VPg) of LSc, 2ab strain migrates faster than capsid protein VP4 (mol. wt. 7000 to 8000) in a polyacrylamide gel and is thus similar to the VPg of the wild-type virus.", "contents": "Possible point mutation sites in LSc, 2ab poliovirus RNA and a protein covalently linked to the 5'-terminus. Poliovirus type I, vaccine strain (LSc, 2ab), which is a temperature- and actinomycin D-sensitive mutant derived from type I Mahoney strain, was grown in HeLa cells in the presence of 32P and a low concentration of actinomycin D. Seven and a half h p.i., genome 32P-RNA was recovered from the purified virion. Analysis of RNase TI digests of the RNA by two-dimensional gel electrophoresis revealed that three possible point mutation sites exist in the large and unique oligonucleotides in the fingerprint. Neither a capping structure nor a nucleotide such as pppNp, ppNp or pNp, was detected by ion exchange column chromatography at pH 5.0 after digestion of virion RNA with RNase T2. Instead, a 32P-labelled compound, which could be digested with Pronase or proteinase K, was eluted at the void volume of the column. Proteinase K digests of the 32P-labelled compound contained pUp or pU as a single labelled c\"mpound, when genome RNA was digested with RNase T2 or nuclease P1, respectively, before digestion with the proteinase. Our data locate possible point mutation sites on the genome of a mutant strain (LSc, 2ab) of type I poliovirus and show that a protein (VPg) is covalently bound to the 5'-terminus of RNA. The protein (VPg) of LSc, 2ab strain migrates faster than capsid protein VP4 (mol. wt. 7000 to 8000) in a polyacrylamide gel and is thus similar to the VPg of the wild-type virus."}
{"id": "PMID:230299", "title": "Comparative studies on Marek's disease virus and herpesvirus of turkey DNAs.", "content": "DNA of Marek's disease virus (MDV) was compared to that of herpes virus of turkey (HVT). Centrifugation of the two virus DNAs in neutral glycerol and CsCl density gradients showed that the MDV genome was slightly larger than that of HVT and that the buoyant density (1.705 g/ml) of MDV DNA in CsCl gradients was slightly lower than that (1.707 g/ml) of HVT DNA. MDV and HVT DNAs were digested with either EcoRI or HindIII restriction endonuclease and analysed by 0.5% agarose gel electrophoresis. The cleavage patterns of HindIII or EcoRI DNA digests of two strains of these two viruses showed general similarities between the strains, but not between MDV and HVT. However, a few fragments of EcoRI or HindIII digests of MDV DNA co-migrated with those of HVT DNA. DNA-DNA reassociation kinetics and DNA-RNA hybridization between the two viruses indicated that MDV and HVT DNAs share detectable homology, although it is less than 5%. The DNA of a HVT variant, which has lost the ability to protect chickens from Marek's disease, appeared similar to DNA of the vaccine strain in the size buoyant density and in its restriction endonuclease cleavage pattern.", "contents": "Comparative studies on Marek's disease virus and herpesvirus of turkey DNAs. DNA of Marek's disease virus (MDV) was compared to that of herpes virus of turkey (HVT). Centrifugation of the two virus DNAs in neutral glycerol and CsCl density gradients showed that the MDV genome was slightly larger than that of HVT and that the buoyant density (1.705 g/ml) of MDV DNA in CsCl gradients was slightly lower than that (1.707 g/ml) of HVT DNA. MDV and HVT DNAs were digested with either EcoRI or HindIII restriction endonuclease and analysed by 0.5% agarose gel electrophoresis. The cleavage patterns of HindIII or EcoRI DNA digests of two strains of these two viruses showed general similarities between the strains, but not between MDV and HVT. However, a few fragments of EcoRI or HindIII digests of MDV DNA co-migrated with those of HVT DNA. DNA-DNA reassociation kinetics and DNA-RNA hybridization between the two viruses indicated that MDV and HVT DNAs share detectable homology, although it is less than 5%. The DNA of a HVT variant, which has lost the ability to protect chickens from Marek's disease, appeared similar to DNA of the vaccine strain in the size buoyant density and in its restriction endonuclease cleavage pattern."}
{"id": "PMID:230300", "title": "The influence of host adaptation of Rous sarcoma virus on the transfecting activity of its DNA provirus.", "content": "Mammalian cells transformed with either Prague strain Rous sarcoma virus of subgroup C (XC cells) or Schmidt-Ruppin strain Rous sarcoma virus of subgroup D (RSCH cells) yielded virus upon fusion with chick cells. Virus was also rescued by transfection of DNA from these cells on to chick cells. However, virus rescue did not occur upon transfection of duck cells, and fusion with duck cells led to virus rescue only from RSCH and not from XC cells. To investigate this restriction on the duck cells the non-defective Prague strain of Rous sarcoma virus of subgroup C (PR-RSV-C) was adapted for efficient replication in duck embryo cells (daPR-RSV-C) by long-term passage in vitro. However, a second PR-RSV-C isolate, rescued from the rat XC sarcoma line (XC DNA 940 virus), failed to adapt to growth in duck cells. When transformed with daPR-RSV-C, which replicates in duck cells as well as in brown leghorn embryo (BLEF) cells, duck cells yielded DNA which transfects fresh duck cells, in contrast to DNA isolated from chicken or duck cells transformed with parental PR-RSV-C.", "contents": "The influence of host adaptation of Rous sarcoma virus on the transfecting activity of its DNA provirus. Mammalian cells transformed with either Prague strain Rous sarcoma virus of subgroup C (XC cells) or Schmidt-Ruppin strain Rous sarcoma virus of subgroup D (RSCH cells) yielded virus upon fusion with chick cells. Virus was also rescued by transfection of DNA from these cells on to chick cells. However, virus rescue did not occur upon transfection of duck cells, and fusion with duck cells led to virus rescue only from RSCH and not from XC cells. To investigate this restriction on the duck cells the non-defective Prague strain of Rous sarcoma virus of subgroup C (PR-RSV-C) was adapted for efficient replication in duck embryo cells (daPR-RSV-C) by long-term passage in vitro. However, a second PR-RSV-C isolate, rescued from the rat XC sarcoma line (XC DNA 940 virus), failed to adapt to growth in duck cells. When transformed with daPR-RSV-C, which replicates in duck cells as well as in brown leghorn embryo (BLEF) cells, duck cells yielded DNA which transfects fresh duck cells, in contrast to DNA isolated from chicken or duck cells transformed with parental PR-RSV-C."}
{"id": "PMID:230301", "title": "Adenovirus-associated virus structural protein sequence homology.", "content": "Adenovirus-associated virus (AAV) structural proteins (VP1, VP2, and VP3) have been examined to determine if areas of sequence homology exist between these three virion proteins. Tryptic and chymotryptic maps have been produced which demonstrate extensive areas of sequence homology common to all three proteins. The amino acid compositions of the proteins were also determined and were found to be very similar. These data are consistent with the hypothesis that all three virion proteins arise either from a common precursor of similar transcripts.", "contents": "Adenovirus-associated virus structural protein sequence homology. Adenovirus-associated virus (AAV) structural proteins (VP1, VP2, and VP3) have been examined to determine if areas of sequence homology exist between these three virion proteins. Tryptic and chymotryptic maps have been produced which demonstrate extensive areas of sequence homology common to all three proteins. The amino acid compositions of the proteins were also determined and were found to be very similar. These data are consistent with the hypothesis that all three virion proteins arise either from a common precursor of similar transcripts."}
{"id": "PMID:230302", "title": "Similarities in the structural organization of the genomes of stumptailed macaque virus (strain HD) and simian virus 40.", "content": "Members of the SV40-polyoma subgroup of papovaviruses share homologous sequences which have been conserved during evolution. The genome of HD virus displays homologies both to the origin of SV40 DNA replication and to the region coding for the VPI capsid protein. As in the case of SV40, both regions are discontinuously arranged in the HD genome.", "contents": "Similarities in the structural organization of the genomes of stumptailed macaque virus (strain HD) and simian virus 40. Members of the SV40-polyoma subgroup of papovaviruses share homologous sequences which have been conserved during evolution. The genome of HD virus displays homologies both to the origin of SV40 DNA replication and to the region coding for the VPI capsid protein. As in the case of SV40, both regions are discontinuously arranged in the HD genome."}
{"id": "PMID:230303", "title": "Anticellular effects of 9-(2-hydroxyethoxymethyl) guanine against herpes simplex virus-transformed cells.", "content": "The guanine derivative 9-(2-hydroxyethoxymethyl) guanine (acycloguanosine), a potent inhibitor of herpes simplex virus (HSV) multiplication, was found to have marked anticellular activity against HSV-transformed thymidine kinase-positive cells. HSV type I-transformed cells were more sensitive to the drug than HSV type 2-transformed cells.", "contents": "Anticellular effects of 9-(2-hydroxyethoxymethyl) guanine against herpes simplex virus-transformed cells. The guanine derivative 9-(2-hydroxyethoxymethyl) guanine (acycloguanosine), a potent inhibitor of herpes simplex virus (HSV) multiplication, was found to have marked anticellular activity against HSV-transformed thymidine kinase-positive cells. HSV type I-transformed cells were more sensitive to the drug than HSV type 2-transformed cells."}
{"id": "PMID:230304", "title": "Inactivation of human cytomegalovirus by the chemical carcinogen 4-nitroquinoline 1-oxide.", "content": "The infectivity of cytomegalovirus (CMV), strain Davis, was inactivated by 4-nitroquinoline 1-oxide (NQO). A series of survival curves indicates that the rate of inactivation was directly dependent on the concentration of NQO over a range of 5 to 200 microgram/ml. At concentrations of I microgram/ml or less, inactivation of virus stock was not observed and at concentrations in excess of 200 microgram/ml, the cellular toxicity of residual NQO prevented quantification of the relatively low surviving infectivity. At a concentration of 200 microgram/ml NQO or less, the loss of virus infectivity could be clearly shown to result from the interaction of NQO with virus and not with cells, since the addition of similar doses of NQO to assay cells simultaneously with virus did not adversely affect the sensitivity of the assay cells to measure virus infectivity. Similarly, the dimethylsulphoxide carrier at concentrations of 5% or less was shown to have a negligible effect on both virus infectivity and on the sensitivity of human skin muscle cells to assay virus infectivity. NQO inactivation of virus infectivity appeared to depend very little on white light, since the kinetics of inactivation in the presence and in the absence of white light were similar.", "contents": "Inactivation of human cytomegalovirus by the chemical carcinogen 4-nitroquinoline 1-oxide. The infectivity of cytomegalovirus (CMV), strain Davis, was inactivated by 4-nitroquinoline 1-oxide (NQO). A series of survival curves indicates that the rate of inactivation was directly dependent on the concentration of NQO over a range of 5 to 200 microgram/ml. At concentrations of I microgram/ml or less, inactivation of virus stock was not observed and at concentrations in excess of 200 microgram/ml, the cellular toxicity of residual NQO prevented quantification of the relatively low surviving infectivity. At a concentration of 200 microgram/ml NQO or less, the loss of virus infectivity could be clearly shown to result from the interaction of NQO with virus and not with cells, since the addition of similar doses of NQO to assay cells simultaneously with virus did not adversely affect the sensitivity of the assay cells to measure virus infectivity. Similarly, the dimethylsulphoxide carrier at concentrations of 5% or less was shown to have a negligible effect on both virus infectivity and on the sensitivity of human skin muscle cells to assay virus infectivity. NQO inactivation of virus infectivity appeared to depend very little on white light, since the kinetics of inactivation in the presence and in the absence of white light were similar."}
{"id": "PMID:230305", "title": "Absence of significant antiviral effects of beta-gamma-methylene GTP on encephalomyocarditis virus infection of L cells and mice.", "content": "The protein synthesis inhibitor beta-gamma-methylene guanosine triphosphate (Gpp-CH2p) is shown here to be ineffective as a 'leaky membrane' antiviral agent against encephalomyocarditis virus infection of L cells and mice. Studies with GppCH2p in encephalomyocarditis virus-infected L cells indicate that the cells only become permeable to the inhibitor late in infection because the compound significantly inhibits protein synthesis only when added at 4 h p.i. At this time 50 to 70% of the new infectious virus particles have already been synthesized, and this is reflected in maximum inhibition of virus yields of only about 40%. Moreover, comparison of inhibition of protein synthesis by GppCH2p in vitro and in cell cultures indicates that the intracellular concentration attained is only 0.25% of that in the medium. The lack of antiviral activity of GppCH2p in encephalomyocarditis virus-infected mice is probably due to leakiness of infected cells occurring too late for sufficient inhibition of virus synthesis to be obtained.", "contents": "Absence of significant antiviral effects of beta-gamma-methylene GTP on encephalomyocarditis virus infection of L cells and mice. The protein synthesis inhibitor beta-gamma-methylene guanosine triphosphate (Gpp-CH2p) is shown here to be ineffective as a 'leaky membrane' antiviral agent against encephalomyocarditis virus infection of L cells and mice. Studies with GppCH2p in encephalomyocarditis virus-infected L cells indicate that the cells only become permeable to the inhibitor late in infection because the compound significantly inhibits protein synthesis only when added at 4 h p.i. At this time 50 to 70% of the new infectious virus particles have already been synthesized, and this is reflected in maximum inhibition of virus yields of only about 40%. Moreover, comparison of inhibition of protein synthesis by GppCH2p in vitro and in cell cultures indicates that the intracellular concentration attained is only 0.25% of that in the medium. The lack of antiviral activity of GppCH2p in encephalomyocarditis virus-infected mice is probably due to leakiness of infected cells occurring too late for sufficient inhibition of virus synthesis to be obtained."}
{"id": "PMID:230306", "title": "Protease activity on the surface of HSV-infected cells.", "content": "Monolayers of primary rabbit kidney cells infected with HSV type I bound lymphoblastoid (Raji) cells, to which the third component (C3) of the complement system had been attached (Raji-C3). This induction of cell contact did not occur on non-infected monolayers and was dependent on C3. The interaction could be suppressed by the presence of protease inhibitors (1 mM-TLCK or-PMSF). The results are interpreted as indicating de novo expression of protease activity on the surface of HSV-infected cells. This protease is characterized by its potential to activate C3 and its inhibition by TLCK.", "contents": "Protease activity on the surface of HSV-infected cells. Monolayers of primary rabbit kidney cells infected with HSV type I bound lymphoblastoid (Raji) cells, to which the third component (C3) of the complement system had been attached (Raji-C3). This induction of cell contact did not occur on non-infected monolayers and was dependent on C3. The interaction could be suppressed by the presence of protease inhibitors (1 mM-TLCK or-PMSF). The results are interpreted as indicating de novo expression of protease activity on the surface of HSV-infected cells. This protease is characterized by its potential to activate C3 and its inhibition by TLCK."}
{"id": "PMID:230307", "title": "Studies on antiviral glycosides, 4. Inhibition of the multiplication of paramyxoviruses by phenyl-6-chloro-6-deoxy-beta-D-glucopyranoside.", "content": "The antiviral activity of phenyl-6-chloro-6-deoxy-beta-D-glucopyranoside (PCG) was studied. PCG specifically inhibited the growth of paramyxoviruses including Sendai, measles and Newcastle disease viruses in LLCMK2 cells at a concentration of 0.5 to 1.0 mM, but did not restrict the multiplication of other RNA viruses (influenza, vesicular stomatitis and polio viruses) at these concentrations. PCG might act in the late stage during virus replication of Sendai virus as it did not inhibit virus RNA and protein synthesis in the infected cells. Comparative studies on the biological properties of virus particles grown in the presence and absence of PCG demonstrated that treatment with it caused the formation of non-haemagglutinating particles.", "contents": "Studies on antiviral glycosides, 4. Inhibition of the multiplication of paramyxoviruses by phenyl-6-chloro-6-deoxy-beta-D-glucopyranoside. The antiviral activity of phenyl-6-chloro-6-deoxy-beta-D-glucopyranoside (PCG) was studied. PCG specifically inhibited the growth of paramyxoviruses including Sendai, measles and Newcastle disease viruses in LLCMK2 cells at a concentration of 0.5 to 1.0 mM, but did not restrict the multiplication of other RNA viruses (influenza, vesicular stomatitis and polio viruses) at these concentrations. PCG might act in the late stage during virus replication of Sendai virus as it did not inhibit virus RNA and protein synthesis in the infected cells. Comparative studies on the biological properties of virus particles grown in the presence and absence of PCG demonstrated that treatment with it caused the formation of non-haemagglutinating particles."}
{"id": "PMID:230308", "title": "Detection of virus antigens in Swiss albino mice infected by milk-borne mouse mammary tumour virus: the effect of age, sex and reproductive status. I. Localization by immunofluorescence of four antigens in mammary tissues and other organs.", "content": "The indirect immunofluorescence technique was used to investigate the expression of virus antigens in a Swiss albino mouse strain infected by mouse mammary tumour virus (MMTV). The antisera used were monospecific for: the glycopolypeptides gp160 and gp47, and the internal polypeptides p28 and p8. In mice infected with milk-borne MMTV, all four antigens were detected in the mammary gland during the first pregnancy and then throughout life, and in mammary tumours. Antigen gp160, located at the secretory border of all glandular cells, is shared by the plasma membrane of the mammary cell, whether virus-producing or not, and by the virus envelope, as shown by the use of absorbed antisera. The other three antigens are virus-specific. Anti-p47 serum stained the secretory border of cells whereas the fluorescence related to p28 and p8 consisted of a few large intracytoplasmic spots. The specific antibodies for p28 and p8 were only absorbed by disrupted virions, confirming that these polypeptides are internal antigens. With serial sections of glands from pregnant and old female mice, the alveoli stained with anti-p28 or anti-p8 serum were found to react also with anti-gp47 serum. However, during lactation, the presence of p28 and p8 could not be detected in the alveoli stained with anti-gp47 serum. Thus, infected alveoli express virus antigens differently. In the mammary glands of all mice studied, some alveoli did not display any staining when the latter three antisera were used. The specific antigenic pattern, maintained in differentiated mammary tumours, became a diffuse and unlocalized staining after transformation into the undifferentiated state. With the exception of the kidney, where gp47 was found in the glomeruli, all other organs of the mouse did not stain with any of the antisera. The presence of gp47 in the glomeruli, probably related to immune-complex deposits, increases with the age of the mouse and is most noticeable in tumour-bearing females. In mice free of milk-borne MMTV, examined during the first week of lactation, antigen gp47 could not be detected. Internal antigens p28 and p8 were detected in nearly all mammary cells as numerous small cytoplasmic dots. This suggests a limited expression of an endogenous virus genome; this expression would be modified when milk-borne virus is produced.", "contents": "Detection of virus antigens in Swiss albino mice infected by milk-borne mouse mammary tumour virus: the effect of age, sex and reproductive status. I. Localization by immunofluorescence of four antigens in mammary tissues and other organs. The indirect immunofluorescence technique was used to investigate the expression of virus antigens in a Swiss albino mouse strain infected by mouse mammary tumour virus (MMTV). The antisera used were monospecific for: the glycopolypeptides gp160 and gp47, and the internal polypeptides p28 and p8. In mice infected with milk-borne MMTV, all four antigens were detected in the mammary gland during the first pregnancy and then throughout life, and in mammary tumours. Antigen gp160, located at the secretory border of all glandular cells, is shared by the plasma membrane of the mammary cell, whether virus-producing or not, and by the virus envelope, as shown by the use of absorbed antisera. The other three antigens are virus-specific. Anti-p47 serum stained the secretory border of cells whereas the fluorescence related to p28 and p8 consisted of a few large intracytoplasmic spots. The specific antibodies for p28 and p8 were only absorbed by disrupted virions, confirming that these polypeptides are internal antigens. With serial sections of glands from pregnant and old female mice, the alveoli stained with anti-p28 or anti-p8 serum were found to react also with anti-gp47 serum. However, during lactation, the presence of p28 and p8 could not be detected in the alveoli stained with anti-gp47 serum. Thus, infected alveoli express virus antigens differently. In the mammary glands of all mice studied, some alveoli did not display any staining when the latter three antisera were used. The specific antigenic pattern, maintained in differentiated mammary tumours, became a diffuse and unlocalized staining after transformation into the undifferentiated state. With the exception of the kidney, where gp47 was found in the glomeruli, all other organs of the mouse did not stain with any of the antisera. The presence of gp47 in the glomeruli, probably related to immune-complex deposits, increases with the age of the mouse and is most noticeable in tumour-bearing females. In mice free of milk-borne MMTV, examined during the first week of lactation, antigen gp47 could not be detected. Internal antigens p28 and p8 were detected in nearly all mammary cells as numerous small cytoplasmic dots. This suggests a limited expression of an endogenous virus genome; this expression would be modified when milk-borne virus is produced."}
{"id": "PMID:230309", "title": "Detection of virus antigens in Swiss albino mice infected by milk-borne mouse mammary tumour virus: the effect of age, sex and reproductive status. II. Radioimmunoassay of two virus components, gp47 and p28 in serum and organ extracts.", "content": "Extracts of various organs, mammary tumours and sera from milk-borne MMTV infected Swiss albino mice of different age, sex and physiological conditions were tested by radioimmunoassay for the presence of gp47, the main envelope polypeptide, and p28, the main core protein of the virus. Except in brain, ovaries and testes, both antigens were found in all organs of old animals and of females after the onset of their first pregnancy. Antigens were not present in organs of weanlings or in whole foetuses. Higher values were found in mammary glands, mammary tumours, epididymis and seminal vesicles. These organs also harboured a greater amount of gp47 than p28. The serum generally contained gp47 but rarely p28. This indicates that gp47 is not virion-bound in blood. Pregnancy, lactation and especially the presence of mammary tumours increased the concentration of gp47 in serum. The results do not allow localization of target organs of MMTV infection in the interval between ingestion of the virus by the suckling mouse and the first pregnancy. Moreover, results obtained with one group of mice devoid of exogenous virus show that, as endogenous MMTV genome expresses p28, it might account for part of the p28 detected exogenous MMTV-infected mice.", "contents": "Detection of virus antigens in Swiss albino mice infected by milk-borne mouse mammary tumour virus: the effect of age, sex and reproductive status. II. Radioimmunoassay of two virus components, gp47 and p28 in serum and organ extracts. Extracts of various organs, mammary tumours and sera from milk-borne MMTV infected Swiss albino mice of different age, sex and physiological conditions were tested by radioimmunoassay for the presence of gp47, the main envelope polypeptide, and p28, the main core protein of the virus. Except in brain, ovaries and testes, both antigens were found in all organs of old animals and of females after the onset of their first pregnancy. Antigens were not present in organs of weanlings or in whole foetuses. Higher values were found in mammary glands, mammary tumours, epididymis and seminal vesicles. These organs also harboured a greater amount of gp47 than p28. The serum generally contained gp47 but rarely p28. This indicates that gp47 is not virion-bound in blood. Pregnancy, lactation and especially the presence of mammary tumours increased the concentration of gp47 in serum. The results do not allow localization of target organs of MMTV infection in the interval between ingestion of the virus by the suckling mouse and the first pregnancy. Moreover, results obtained with one group of mice devoid of exogenous virus show that, as endogenous MMTV genome expresses p28, it might account for part of the p28 detected exogenous MMTV-infected mice."}
{"id": "PMID:230311", "title": "Cell cycle-dependent chronic infection of human cytomegalovirus in human osteogenic sarcoma cells.", "content": "Human osteogenic sarcoma cells transformed by murine sarcoma virus (R970) showed restricted growth of human cytomegalovirus (HCMV). Virus was attached to the same extent as in human fibroblasts. HCMV growth was blocked at early stages after virus penetration. Splitting of infected R970 cultures resulted in infection of all cells. In experiments using synchronized R970 cells it was found that factor(s) associated with the S-phase of the cell cycle might be necessary for establishment of the infection.", "contents": "Cell cycle-dependent chronic infection of human cytomegalovirus in human osteogenic sarcoma cells. Human osteogenic sarcoma cells transformed by murine sarcoma virus (R970) showed restricted growth of human cytomegalovirus (HCMV). Virus was attached to the same extent as in human fibroblasts. HCMV growth was blocked at early stages after virus penetration. Splitting of infected R970 cultures resulted in infection of all cells. In experiments using synchronized R970 cells it was found that factor(s) associated with the S-phase of the cell cycle might be necessary for establishment of the infection."}
{"id": "PMID:230312", "title": "Selective replication of transformation-defective avian sarcoma virus mutants in duck embryo fibroblasts.", "content": "When an avian sarcoma virus (ASV), subgroup C Bratislava 77 (B77-C) was inoculated into duck embryo fibroblast cultures (DEF) at a m.o.i. of 0.02, its replication was retarded by about 3 days compared with that in chick embryo fibroblast cultures (CEF). A transformation-defective (td) mutant was isolated during this period of retardation. Unlike the sarcoma virus, this td mutant replicated in both DEF and CEF with no retardation, even at a low m.o.i. The subgroup C Prague strain of Rous sarcoma virus (PR-C), which can infect DEF, also replicated in DEF slower than its td mutant, tdPR-C, at a m.o.i. of 0.02.", "contents": "Selective replication of transformation-defective avian sarcoma virus mutants in duck embryo fibroblasts. When an avian sarcoma virus (ASV), subgroup C Bratislava 77 (B77-C) was inoculated into duck embryo fibroblast cultures (DEF) at a m.o.i. of 0.02, its replication was retarded by about 3 days compared with that in chick embryo fibroblast cultures (CEF). A transformation-defective (td) mutant was isolated during this period of retardation. Unlike the sarcoma virus, this td mutant replicated in both DEF and CEF with no retardation, even at a low m.o.i. The subgroup C Prague strain of Rous sarcoma virus (PR-C), which can infect DEF, also replicated in DEF slower than its td mutant, tdPR-C, at a m.o.i. of 0.02."}
{"id": "PMID:230313", "title": "Synaptic connections and functional organization in Aplysia buccal ganglia.", "content": "The buccal ganglion of Aplysia contains three morpho-functional groups (A, B, and C) of large cells and two groups (s1 and s2) of small cells. The A cells evoke monoxynaptic IPSPs in the B cells. We found that s1 cells can evoke large EPSPs in the A cells, IEPSPs in the B cells, and EIIPSPs in the C cells; several s1 cells are able to evoke all three types of responses. Many s2 cells can evoke these same responses, but only in the A and B cells. Furthermore, the s cells can evoke depolarizing PSPs in other s cells; this relation is often reciprocal. All these responses may also be contralateral. Their monosynaptic nature is shown by the consistent 1:1 relationship with the presynaptic spike, and also by the effects of intracellular tetraethylammonium and of high Mg2+ concentration in the bathing medium. d-tubocurarine reversibly suppresses the I phase of the IEPSP evoked by the s cells in the B cells. All the responses evoked by the s cells undergo depression with repetition. The network formed by all these relations is outlined, and a double relationship proposed between s cells and B cells. By electrophysiological tracing of axonal pathways it is shown that the A cells send axons into the 3rd buccal nerve, the B cells into the 2nd and/or 3rd buccal nerve and in two cases into the radular nerve, and the C cells into the gastro-oesophageal nerve. Spontaneous synaptic activity of the buccal neurons appears to be formed mostly by the described PSPs. Spontaneous firing inside the isolated ganglion corresponds well to the alternate pattern of muscular contractions of the buccal mass.", "contents": "Synaptic connections and functional organization in Aplysia buccal ganglia. The buccal ganglion of Aplysia contains three morpho-functional groups (A, B, and C) of large cells and two groups (s1 and s2) of small cells. The A cells evoke monoxynaptic IPSPs in the B cells. We found that s1 cells can evoke large EPSPs in the A cells, IEPSPs in the B cells, and EIIPSPs in the C cells; several s1 cells are able to evoke all three types of responses. Many s2 cells can evoke these same responses, but only in the A and B cells. Furthermore, the s cells can evoke depolarizing PSPs in other s cells; this relation is often reciprocal. All these responses may also be contralateral. Their monosynaptic nature is shown by the consistent 1:1 relationship with the presynaptic spike, and also by the effects of intracellular tetraethylammonium and of high Mg2+ concentration in the bathing medium. d-tubocurarine reversibly suppresses the I phase of the IEPSP evoked by the s cells in the B cells. All the responses evoked by the s cells undergo depression with repetition. The network formed by all these relations is outlined, and a double relationship proposed between s cells and B cells. By electrophysiological tracing of axonal pathways it is shown that the A cells send axons into the 3rd buccal nerve, the B cells into the 2nd and/or 3rd buccal nerve and in two cases into the radular nerve, and the C cells into the gastro-oesophageal nerve. Spontaneous synaptic activity of the buccal neurons appears to be formed mostly by the described PSPs. Spontaneous firing inside the isolated ganglion corresponds well to the alternate pattern of muscular contractions of the buccal mass."}
{"id": "PMID:230314", "title": "Effects of amino acids on calcium uptake by glial and neuroblastoma cells.", "content": "The uptake of [45Ca] has been studied in clonal glial and neuronal cells. It was somewhat more efficient in the neuroblastoma clone M1 compared to glial clones. In all cases [45Ca] uptake was shown to depend on the phosphate concentration in the incubation medium. It was decreased by the ionophore A 23187  at 200 microM concentration in both neuronal and glial clones. The influence of amino acids some of which are putative neurotransmitters was investigated; the interactions between [45Ca] uptake and these amino acids were related to their concentration and the type of cells used (neuronal or glial). L-aspartate and taurine for example had two opposite effects on [45Ca] uptake by the glial clone NN at two different concentrations; they could therefore play a role in the control of calcium level in the synaptic cleft.", "contents": "Effects of amino acids on calcium uptake by glial and neuroblastoma cells. The uptake of [45Ca] has been studied in clonal glial and neuronal cells. It was somewhat more efficient in the neuroblastoma clone M1 compared to glial clones. In all cases [45Ca] uptake was shown to depend on the phosphate concentration in the incubation medium. It was decreased by the ionophore A 23187  at 200 microM concentration in both neuronal and glial clones. The influence of amino acids some of which are putative neurotransmitters was investigated; the interactions between [45Ca] uptake and these amino acids were related to their concentration and the type of cells used (neuronal or glial). L-aspartate and taurine for example had two opposite effects on [45Ca] uptake by the glial clone NN at two different concentrations; they could therefore play a role in the control of calcium level in the synaptic cleft."}
{"id": "PMID:230315", "title": "Mg++-sensitivity of neuromuscular transmission in two crustaceans: correlation with blood Mg++ levels.", "content": "Neuromuscular transmission was measured in muscles of spider crabs (Hyas areneus) and lobsters (Homarus americanus). Solutions containing 40 and 10 mM/1 Mg++, which were approximately the same as those measured in the blood of Hyas and Homarus, respectively, were used to soak the preparations prior to testing. In Homarus, neuromuscular transmission was severely depressed by 40 mM Mg++. In spider crabs, neuromuscular transmission was not severely depressed. Although the amount of transmitter released by nerve impulses was reduced, total membrane depolarization during trains of impulses was not reduced because a compensating increase in muscle fiber membrane resistance occurred in Hyas preparations exposed to M Mg++. Hyas, but not Homarus, is physiologically adapted to function at relatively high blood Mg++ concentrations.", "contents": "Mg++-sensitivity of neuromuscular transmission in two crustaceans: correlation with blood Mg++ levels. Neuromuscular transmission was measured in muscles of spider crabs (Hyas areneus) and lobsters (Homarus americanus). Solutions containing 40 and 10 mM/1 Mg++, which were approximately the same as those measured in the blood of Hyas and Homarus, respectively, were used to soak the preparations prior to testing. In Homarus, neuromuscular transmission was severely depressed by 40 mM Mg++. In spider crabs, neuromuscular transmission was not severely depressed. Although the amount of transmitter released by nerve impulses was reduced, total membrane depolarization during trains of impulses was not reduced because a compensating increase in muscle fiber membrane resistance occurred in Hyas preparations exposed to M Mg++. Hyas, but not Homarus, is physiologically adapted to function at relatively high blood Mg++ concentrations."}
{"id": "PMID:230316", "title": "Neurotoxicity of halogenated hydroxyquinolines: clinical analysis of cases reported outside Japan.", "content": "An analysis is presented of 220 cases of possible neurotoxic reactions to halogenated hydroxyquinolines reported from outside Japan. In 80 cases insufficient information was available for adequate comment and in 29 a relationship to the administration of clioquinol could be excluded. Of the remainder, a relationship to clioquinol was considered probable in 42 and possible in 69 cases. In six of the probable cases the neurological disturbance consisted of an acute reversible encephalopathy usually related to the ingestion of a high dose of clioquinol over a short period. The most common manifestation, observed in 15 further cases, was isolated optic atrophy. This was most frequently found in children, many of whom had received clioquinol as treatment for acrodermatitis enteropathica. In the remaining cases, a combination of myelopathy, visual disturbance, and peripheral neuropathy was the most common manifestation. Isolated myelopathy or peripheral neuropathy, or these manifestations occurring together, were infrequent. The onset of all manifestations (except toxic encephalopathy) was usually subacute, with subsequent partial recovery. Older subjects tended to display more side effects. The full syndrome of subacute myelo-optic neuropathy was more frequent in women, but they tended to have taken greater quantities of the drug.", "contents": "Neurotoxicity of halogenated hydroxyquinolines: clinical analysis of cases reported outside Japan. An analysis is presented of 220 cases of possible neurotoxic reactions to halogenated hydroxyquinolines reported from outside Japan. In 80 cases insufficient information was available for adequate comment and in 29 a relationship to the administration of clioquinol could be excluded. Of the remainder, a relationship to clioquinol was considered probable in 42 and possible in 69 cases. In six of the probable cases the neurological disturbance consisted of an acute reversible encephalopathy usually related to the ingestion of a high dose of clioquinol over a short period. The most common manifestation, observed in 15 further cases, was isolated optic atrophy. This was most frequently found in children, many of whom had received clioquinol as treatment for acrodermatitis enteropathica. In the remaining cases, a combination of myelopathy, visual disturbance, and peripheral neuropathy was the most common manifestation. Isolated myelopathy or peripheral neuropathy, or these manifestations occurring together, were infrequent. The onset of all manifestations (except toxic encephalopathy) was usually subacute, with subsequent partial recovery. Older subjects tended to display more side effects. The full syndrome of subacute myelo-optic neuropathy was more frequent in women, but they tended to have taken greater quantities of the drug."}
{"id": "PMID:230317", "title": "Soleus motoneurone excitability in man: an indirect approach for obtaining quantitative data.", "content": "Using combinations of H and T reflexes, spatial summation has been studied in the human soleus motoneurone pool. With certain assumptions, mathematical treatment of the results yielded estimates of the thresholds of motoneurones to monosynaptic activation by Ia nerve fibres. It was found that, on average, about 62 EPSPs were required to discharge a motoneurone and that a single Ia fibre supplied about 139 neurones.", "contents": "Soleus motoneurone excitability in man: an indirect approach for obtaining quantitative data. Using combinations of H and T reflexes, spatial summation has been studied in the human soleus motoneurone pool. With certain assumptions, mathematical treatment of the results yielded estimates of the thresholds of motoneurones to monosynaptic activation by Ia nerve fibres. It was found that, on average, about 62 EPSPs were required to discharge a motoneurone and that a single Ia fibre supplied about 139 neurones."}
{"id": "PMID:230318", "title": "Neuromuscular transmission in thyrotoxicosis.", "content": "The occurrence of thyrotoxicosis in myasthenia gravis is estimated as 5.3% (Osserman et al. 1967) but the incidence of myasthenia in the course of thyrotoxicosis is only 0.2% (Simpson 1968). The association between these two diseases is not a chance one and there are two possible basic mechanisms viz. the action of thyroid hormone on the neuromuscular junction or the existence of a cause common to both. The fatigability seen clinically in thyrotoxic myopathy could be partly attributed to myasthenia. With these possibilities in mind, a search for electromyographic stigmata of latent myasthenia was done on 48 consecutive cases of hyperthyroidism who also had chronic myopathy by performing repeated nerve stimulation. Eight cases had abnormal neuromuscular transmission as in myasthenia gravis and one of these cases later developed clinical myasthenia involving the ocular muscles. Three other cases showed abnormal facilitation as in the Eaton-Lambert syndrome.", "contents": "Neuromuscular transmission in thyrotoxicosis. The occurrence of thyrotoxicosis in myasthenia gravis is estimated as 5.3% (Osserman et al. 1967) but the incidence of myasthenia in the course of thyrotoxicosis is only 0.2% (Simpson 1968). The association between these two diseases is not a chance one and there are two possible basic mechanisms viz. the action of thyroid hormone on the neuromuscular junction or the existence of a cause common to both. The fatigability seen clinically in thyrotoxic myopathy could be partly attributed to myasthenia. With these possibilities in mind, a search for electromyographic stigmata of latent myasthenia was done on 48 consecutive cases of hyperthyroidism who also had chronic myopathy by performing repeated nerve stimulation. Eight cases had abnormal neuromuscular transmission as in myasthenia gravis and one of these cases later developed clinical myasthenia involving the ocular muscles. Three other cases showed abnormal facilitation as in the Eaton-Lambert syndrome."}
{"id": "PMID:230319", "title": "A spin label study of myelin fluidity with normal and pathological peripheral nerves.", "content": "The myelin fluidity in peripheral nerves from normal subjects and patients with neuropathy has been studied. Nerve biopsies were made in subjects without neuropathy and in patients with Guillain-Barr\u00e9, alcoholic or diabetic polyneuropathies and heredodegenerative diseases. The fluidity was studied using a stearic acid spin label with a nitroxide radical at C12 (12-doxylstearic acid) which was introduced by exchange between spin label-charged BSA and nerve myelin. Spectra was obtained with a VARIAN E 109 ESR spectrometer, at temperatures from 5 to 45 degrees C. The ultrastructure of biopsied nerves was also studied. The electron spin resonance (ESR) spectra were all typical of a partially immobilized nitroxide with a distance between outer hyperfine lines (2T//) of about 50 G, at room temperature. The curve 2T// against temperature shows two critical temperatures: 10 and 30 degrees C for all nerves. No correlation could be established between ultrastructure and fluidity of nerves. However, the myelin of nerves from diabetic patients showed a significant increase in viscosity. This physicochemical modification may represent an initial alteration of the myelin sheath, and demands further investigation. No modification of the myelin fluidity was observed in any of the other nerves studied.", "contents": "A spin label study of myelin fluidity with normal and pathological peripheral nerves. The myelin fluidity in peripheral nerves from normal subjects and patients with neuropathy has been studied. Nerve biopsies were made in subjects without neuropathy and in patients with Guillain-Barr\u00e9, alcoholic or diabetic polyneuropathies and heredodegenerative diseases. The fluidity was studied using a stearic acid spin label with a nitroxide radical at C12 (12-doxylstearic acid) which was introduced by exchange between spin label-charged BSA and nerve myelin. Spectra was obtained with a VARIAN E 109 ESR spectrometer, at temperatures from 5 to 45 degrees C. The ultrastructure of biopsied nerves was also studied. The electron spin resonance (ESR) spectra were all typical of a partially immobilized nitroxide with a distance between outer hyperfine lines (2T//) of about 50 G, at room temperature. The curve 2T// against temperature shows two critical temperatures: 10 and 30 degrees C for all nerves. No correlation could be established between ultrastructure and fluidity of nerves. However, the myelin of nerves from diabetic patients showed a significant increase in viscosity. This physicochemical modification may represent an initial alteration of the myelin sheath, and demands further investigation. No modification of the myelin fluidity was observed in any of the other nerves studied."}
{"id": "PMID:230320", "title": "Calcium deposits in the perineurium and their relation to lipid accumulation.", "content": "Calcification of the perineurium in sural nerves occurs in human adults. Deposits of calcium salts can be found focally in the middle and outer layers of the perineurium. Evidence indicates that this calcification is related to nerve fibre breakdown and to the local presence of lipids in the perineurium. The origin of the lipids may be senescent cells or degradation myelin.", "contents": "Calcium deposits in the perineurium and their relation to lipid accumulation. Calcification of the perineurium in sural nerves occurs in human adults. Deposits of calcium salts can be found focally in the middle and outer layers of the perineurium. Evidence indicates that this calcification is related to nerve fibre breakdown and to the local presence of lipids in the perineurium. The origin of the lipids may be senescent cells or degradation myelin."}
{"id": "PMID:230321", "title": "Cyclic nucleotide phosphodiesterase activity in muscle of patients with carcinoma.", "content": "Cyclic nucleotide phosphodiesterase activity has been measured in muscle biopsies taken from healthy controls and from cancer patients. In both groups the muscles were clinically and morphologically normal. The phosphodiesterase activity was significantly increased in muscles from cancer patients using both cyclic AMP and cyclic GMP as substrate. These findings are in line with previous reports indicating that malignancy may interfere with metabolism of the host muscular tissues, and suggest the possibility that the observed biochemical changes might be an aspect of an early muscle neurogenic involvement.", "contents": "Cyclic nucleotide phosphodiesterase activity in muscle of patients with carcinoma. Cyclic nucleotide phosphodiesterase activity has been measured in muscle biopsies taken from healthy controls and from cancer patients. In both groups the muscles were clinically and morphologically normal. The phosphodiesterase activity was significantly increased in muscles from cancer patients using both cyclic AMP and cyclic GMP as substrate. These findings are in line with previous reports indicating that malignancy may interfere with metabolism of the host muscular tissues, and suggest the possibility that the observed biochemical changes might be an aspect of an early muscle neurogenic involvement."}
{"id": "PMID:230322", "title": "Femoral neuropathy due to compression by retroperitoneal haemorrhage: a modern evaluation.", "content": "We report a case of femoral neuropathy due to retroperitoneal haemorrhage occurring during the administration of heaprin. The site of the hematoma is illustrated in the CT scan. It is emphasised that the modern assessment of peripheral neuropathies in the lower limbs associated with retroperitoneal haemorrhage by means of CT scan will promote our understanding of the natural history of this condition.", "contents": "Femoral neuropathy due to compression by retroperitoneal haemorrhage: a modern evaluation. We report a case of femoral neuropathy due to retroperitoneal haemorrhage occurring during the administration of heaprin. The site of the hematoma is illustrated in the CT scan. It is emphasised that the modern assessment of peripheral neuropathies in the lower limbs associated with retroperitoneal haemorrhage by means of CT scan will promote our understanding of the natural history of this condition."}
{"id": "PMID:230323", "title": "Changes in growth and morphology of human gliomas and fibroblasts cultured in D-valine medium.", "content": "Human fibroblasts and cells cultured from a glioblastoma multiforme and and oligodendroglioma were grown in standard tissue culture medium and in a medium in which D-valine was substituted for L-valine (DVM). Growth of all three types of cells was inhibited in DVM. Morphological changes of cells cultured in DVM also occurred: many fibroblasts became stellate-shaped and the oligodendroglioma cells had fewer processes. These findings indicate that DVM can not be used to decrease fibroblastic contamination in cultures of human gliomas without altering the morphological and growth characteristics of the neoplastic cells.", "contents": "Changes in growth and morphology of human gliomas and fibroblasts cultured in D-valine medium. Human fibroblasts and cells cultured from a glioblastoma multiforme and and oligodendroglioma were grown in standard tissue culture medium and in a medium in which D-valine was substituted for L-valine (DVM). Growth of all three types of cells was inhibited in DVM. Morphological changes of cells cultured in DVM also occurred: many fibroblasts became stellate-shaped and the oligodendroglioma cells had fewer processes. These findings indicate that DVM can not be used to decrease fibroblastic contamination in cultures of human gliomas without altering the morphological and growth characteristics of the neoplastic cells."}
{"id": "PMID:230324", "title": "Topography of Pick inclusion bodies in hippocampi of demented patients. A quantitative study.", "content": "Topographic analysis was performed on the distribution of argyrophilic inclusions in hippocampal neurones of patients with Pick's dementia. A semiautomated scanning stage microscope linked potentiometrically to an XY pen recorder permitted the plotting of cytoarchitectonic \"scattergrams\" from the sequentially screened hippocampal formations. The density of Pick body-bearing nerve cells per cubic mm. of (pyramidal) cortex was quantified by measuring the area of each of six \"zones\" with a digitizer and programmable calculator. The ranking orders of relative severity showed that neurones in Rose's H1 field, the adjacent subiculum, and the entorhinal cortex are severely involved; that H2 and the presubiculum are less afflicted; and that the endplate is the least affected of all. The similarity of these predilections to those already demonstrated for Hirano bodies, granulovacuoles and neurofibrillary tangles in Alzheimer's disease suggests that a specific neurotransmitter defect may also underlie the dementia of Pick's disease.", "contents": "Topography of Pick inclusion bodies in hippocampi of demented patients. A quantitative study. Topographic analysis was performed on the distribution of argyrophilic inclusions in hippocampal neurones of patients with Pick's dementia. A semiautomated scanning stage microscope linked potentiometrically to an XY pen recorder permitted the plotting of cytoarchitectonic \"scattergrams\" from the sequentially screened hippocampal formations. The density of Pick body-bearing nerve cells per cubic mm. of (pyramidal) cortex was quantified by measuring the area of each of six \"zones\" with a digitizer and programmable calculator. The ranking orders of relative severity showed that neurones in Rose's H1 field, the adjacent subiculum, and the entorhinal cortex are severely involved; that H2 and the presubiculum are less afflicted; and that the endplate is the least affected of all. The similarity of these predilections to those already demonstrated for Hirano bodies, granulovacuoles and neurofibrillary tangles in Alzheimer's disease suggests that a specific neurotransmitter defect may also underlie the dementia of Pick's disease."}
{"id": "PMID:230325", "title": "The CO2 laser beam in the surgical treatment of cerebral tumours.", "content": "Several cases of supratentorial gliomas and meningiomas were operated on since May 1977 with the help of CO2 laser infrared beam, generated by the Sharplan 791 He unit, with an adjustable output up to 50 Watts. Defocused laser beam has been found to be useful in direct attack on the tumour, through a vaporization of the neoplastic tissue. So the tumour could be progressively excavate with a loss of blood comparatively lower than with classical method. Haemostasis was quite good on diffuse capillary bleeding, but not on arterial or venous haemorragies, where the use of electrocoagulation was necessary. Extirpation especially, of meningiomas, was easier and less traumatic with the laser beam, and the destruction of infiltrating glial tumours was facilitated too.", "contents": "The CO2 laser beam in the surgical treatment of cerebral tumours. Several cases of supratentorial gliomas and meningiomas were operated on since May 1977 with the help of CO2 laser infrared beam, generated by the Sharplan 791 He unit, with an adjustable output up to 50 Watts. Defocused laser beam has been found to be useful in direct attack on the tumour, through a vaporization of the neoplastic tissue. So the tumour could be progressively excavate with a loss of blood comparatively lower than with classical method. Haemostasis was quite good on diffuse capillary bleeding, but not on arterial or venous haemorragies, where the use of electrocoagulation was necessary. Extirpation especially, of meningiomas, was easier and less traumatic with the laser beam, and the destruction of infiltrating glial tumours was facilitated too."}
{"id": "PMID:230330", "title": "The demonstration of alpha lactalbumin in human breast carcinomas.", "content": "Alpha lactalbumin, a good marker of functional differentiation, has been demonstrated in 51 of a 100 human breast carcinomas examined using the immunoperoxidase technique. There is no relationship between production of alpha lactalbumin and histological differentiation, and the absence or presence of lymph-node metastases.", "contents": "The demonstration of alpha lactalbumin in human breast carcinomas. Alpha lactalbumin, a good marker of functional differentiation, has been demonstrated in 51 of a 100 human breast carcinomas examined using the immunoperoxidase technique. There is no relationship between production of alpha lactalbumin and histological differentiation, and the absence or presence of lymph-node metastases."}
{"id": "PMID:230331", "title": "The nature of virus-like particles in the paraxial muscles of idiopathic scoliosis.", "content": "Virus-like particles (VLP) have been identified by electronmicroscopy in the skeletal muscles (paraxials) of six cases of idiopathic scoliosis. These particles closely resembled VLP reported in the skeletal muscles in other conditions, e.g. Reye's syndrome, polymyositis, malignant hyperthermia, and chronic myopathy. We have shown by specific staining that these structures are composed of glycogen in a crystalline form. Using Coxsackie B infected tissue culture cells as a control we have shown that these viruses, which are of similar shape and size to the VLP, were unstained using this specific staining method.", "contents": "The nature of virus-like particles in the paraxial muscles of idiopathic scoliosis. Virus-like particles (VLP) have been identified by electronmicroscopy in the skeletal muscles (paraxials) of six cases of idiopathic scoliosis. These particles closely resembled VLP reported in the skeletal muscles in other conditions, e.g. Reye's syndrome, polymyositis, malignant hyperthermia, and chronic myopathy. We have shown by specific staining that these structures are composed of glycogen in a crystalline form. Using Coxsackie B infected tissue culture cells as a control we have shown that these viruses, which are of similar shape and size to the VLP, were unstained using this specific staining method."}
{"id": "PMID:230333", "title": "Activation by sanguinarine of active sodium efflux from frog skeletal muscle in the presence of ouabain.", "content": "1. Applied to intact Na-rich muscle cells, sanguinarine causes an increased 22Na efflux in the presence or absence of extracellular K+ or of ouabain. 2. The increased 22Na efflux does not represent Na:Na exchange as indicated by the fact that it is not associated with an increase in one-way isotopic Na influx nor is it abolished by the absence of external Na+. 3. In both K-free Ringer and K-free Ringer containing ouabain, sanguinarine not only increases one-way efflux of 22Na, it also induces net efflux of Na+ in the face of both an electrical and a concentration gradient. Moreover, the induction of net Na+ efflux occurs in the face of an approximately fourfold increase in PNa. These surprising results lead to the conclusion that, contrary to all experiments, sanguinarine induces active Na+ efflux even in K-free Ringer containing 10(-3) M-ouabain. 4. Sanguinarine depolarizes the Na-loaded muscle to approximately the same value, -54 mV, regardless of the presence or absence of extracellular K+. This depolarization is most likely secondary to the increase in PNa. 5. Sanguinarine causes a net loss of K+, presumably secondary to the depolarization. 6. The stimulation of net Na+ efflux is not correlated with the depolarization. The stimulation in K-free conditions (with or without ouabain), which is associated with the largest depolarization, produces an increment in net Na+ efflux which is not significantly different from the increment in net Na+ efflux in 10 mM-K+ Ringer where the depolarization is smallest. 7. Although sanguinarine increases active Na+ efflux in intact cells, it inhibits the isolated (Na+ + K+)-ATPase, presumably due to interaction with a site on the inner face of the membrane fragment. 8. The surprising stimulation of active Na+ efflux in the presence of 10(-3) M-ouabain must be due to interaction of sanguinarine with a site on the outer face of the membrane, perhaps the K+ activation site. It seems probable that the component of active Na+ efflux induced by sanguinarine is mediated by the Na pump. Sanguinarine may produce a K+-like effect upon the Na pump with consequent unbinding of ouabain.", "contents": "Activation by sanguinarine of active sodium efflux from frog skeletal muscle in the presence of ouabain. 1. Applied to intact Na-rich muscle cells, sanguinarine causes an increased 22Na efflux in the presence or absence of extracellular K+ or of ouabain. 2. The increased 22Na efflux does not represent Na:Na exchange as indicated by the fact that it is not associated with an increase in one-way isotopic Na influx nor is it abolished by the absence of external Na+. 3. In both K-free Ringer and K-free Ringer containing ouabain, sanguinarine not only increases one-way efflux of 22Na, it also induces net efflux of Na+ in the face of both an electrical and a concentration gradient. Moreover, the induction of net Na+ efflux occurs in the face of an approximately fourfold increase in PNa. These surprising results lead to the conclusion that, contrary to all experiments, sanguinarine induces active Na+ efflux even in K-free Ringer containing 10(-3) M-ouabain. 4. Sanguinarine depolarizes the Na-loaded muscle to approximately the same value, -54 mV, regardless of the presence or absence of extracellular K+. This depolarization is most likely secondary to the increase in PNa. 5. Sanguinarine causes a net loss of K+, presumably secondary to the depolarization. 6. The stimulation of net Na+ efflux is not correlated with the depolarization. The stimulation in K-free conditions (with or without ouabain), which is associated with the largest depolarization, produces an increment in net Na+ efflux which is not significantly different from the increment in net Na+ efflux in 10 mM-K+ Ringer where the depolarization is smallest. 7. Although sanguinarine increases active Na+ efflux in intact cells, it inhibits the isolated (Na+ + K+)-ATPase, presumably due to interaction with a site on the inner face of the membrane fragment. 8. The surprising stimulation of active Na+ efflux in the presence of 10(-3) M-ouabain must be due to interaction of sanguinarine with a site on the outer face of the membrane, perhaps the K+ activation site. It seems probable that the component of active Na+ efflux induced by sanguinarine is mediated by the Na pump. Sanguinarine may produce a K+-like effect upon the Na pump with consequent unbinding of ouabain."}
{"id": "PMID:230335", "title": "Cyclic GMP and the permeability of the disks of the frog photoreceptors.", "content": "1. The diffusion of sodium, potassium and rubidium (not chloride) ions across the disk membrane is increased by cyclic guanosine monophosphate (cyclic GMP). 2. The increase is greater for sodium than for rubidium in the 0.01-0.1 mM concentration range. 3. Cyclic adenosine monophosphate (cyclic AMP) is less efficient than cyclic GMP; GMP and guanosine triphosphate are without effect. 4. The effect is present with either 1.8 mM calcium ions or 4 mM-EGTA in the perfusion fluid. 5. The presence of the cyclic GMP phosphodiesterase on the disk membranes is not needed for this effect. 6. The effect is present in both unbleached and fully bleached membranes.", "contents": "Cyclic GMP and the permeability of the disks of the frog photoreceptors. 1. The diffusion of sodium, potassium and rubidium (not chloride) ions across the disk membrane is increased by cyclic guanosine monophosphate (cyclic GMP). 2. The increase is greater for sodium than for rubidium in the 0.01-0.1 mM concentration range. 3. Cyclic adenosine monophosphate (cyclic AMP) is less efficient than cyclic GMP; GMP and guanosine triphosphate are without effect. 4. The effect is present with either 1.8 mM calcium ions or 4 mM-EGTA in the perfusion fluid. 5. The presence of the cyclic GMP phosphodiesterase on the disk membranes is not needed for this effect. 6. The effect is present in both unbleached and fully bleached membranes."}
{"id": "PMID:230336", "title": "Nephron electrolyte transport and sodium-potassium adenosine triphosphatase activity: influence of nicotine in rat and rabbit.", "content": "1. The influence upon mammalian renal epithelial transport of L-nicotine was studied in different types of experiments. 2. The kidney in situ (rat), when infused with nicotine (1 mg hr-1 kg-1 I.V.), lowered its absolute and fractional K+-absorption significantly and reversibly, but Na+-absorption did not change. Effects on glomerular function and an irreversible effect upon epithelial Na+ and K+ absorption were prevailing at higher infused amounts (10 or 50 mg hr-1 kg-1). 3. Single dissected nephron segments (collecting tubule, rabbit) were perfused in vitro, and the Na+ and K+-transtubular net flux was measured while L-nicotine (50 ng/ml.) had been added to the contraluminal side of the epithelium. Both, Na+-absorption and K+-secretion were decreased reversibly. 4. The activity of the Na+-K+-activated ATPase was significantly decreased in the cortical collecting tubule and in the proximal convoluted tubule of the rabbit after incubation of single in vitro dissected nephron segments with L-nicotine (50 or 100 ng/ml.). In contrast, nicotine added to a homogenate of renal cortical tissue had no effect on the Na+-transport enzyme or on key enzymes of glycolysis and gluconeogenesis. 5. These observations on the kidney in situ and on defined, perfused and non-perfused nephrons in vitro suggest that L-nicotine has dose-dependent, direct epithelial and mediated systemic effects on mammalian renal ion transport.", "contents": "Nephron electrolyte transport and sodium-potassium adenosine triphosphatase activity: influence of nicotine in rat and rabbit. 1. The influence upon mammalian renal epithelial transport of L-nicotine was studied in different types of experiments. 2. The kidney in situ (rat), when infused with nicotine (1 mg hr-1 kg-1 I.V.), lowered its absolute and fractional K+-absorption significantly and reversibly, but Na+-absorption did not change. Effects on glomerular function and an irreversible effect upon epithelial Na+ and K+ absorption were prevailing at higher infused amounts (10 or 50 mg hr-1 kg-1). 3. Single dissected nephron segments (collecting tubule, rabbit) were perfused in vitro, and the Na+ and K+-transtubular net flux was measured while L-nicotine (50 ng/ml.) had been added to the contraluminal side of the epithelium. Both, Na+-absorption and K+-secretion were decreased reversibly. 4. The activity of the Na+-K+-activated ATPase was significantly decreased in the cortical collecting tubule and in the proximal convoluted tubule of the rabbit after incubation of single in vitro dissected nephron segments with L-nicotine (50 or 100 ng/ml.). In contrast, nicotine added to a homogenate of renal cortical tissue had no effect on the Na+-transport enzyme or on key enzymes of glycolysis and gluconeogenesis. 5. These observations on the kidney in situ and on defined, perfused and non-perfused nephrons in vitro suggest that L-nicotine has dose-dependent, direct epithelial and mediated systemic effects on mammalian renal ion transport."}
{"id": "PMID:230332", "title": "Retinal varicosity in Klippel-Trenaunay syndrome.", "content": "A retinal varicosity in the Klippel-Trenaunay syndrome is observed and diagnosed in a 24-year-old female. Fluorescein angiography was used to illustrate and specify the nature of the retinal vascular anomaly.", "contents": "Retinal varicosity in Klippel-Trenaunay syndrome. A retinal varicosity in the Klippel-Trenaunay syndrome is observed and diagnosed in a 24-year-old female. Fluorescein angiography was used to illustrate and specify the nature of the retinal vascular anomaly."}
{"id": "PMID:230350", "title": "Structure--activity relationships of pyrrole amidine antiviral antibiotics. 1. Modifications of the alkylamidine side chain.", "content": "Representatives of three types of side-chain analogues of distamycin A (1) were synthesized. These were tested for cytotoxicity, inhibition of herpes simplex virus (HSV) replication in cultured cells, effects on the synthesis of HSV DNA in isolated nuclei in vitro, as well as on DNA synthesis by purified HSV DNA polymerase. Distamycin A was the most active compound in all three antiviral tests, as well as the most toxic. However, several compounds, in particular the aromatic analogues 15 and 16, showed no toxicity under the experimental conditions used but were still very active in the three antiviral tests.", "contents": "Structure--activity relationships of pyrrole amidine antiviral antibiotics. 1. Modifications of the alkylamidine side chain. Representatives of three types of side-chain analogues of distamycin A (1) were synthesized. These were tested for cytotoxicity, inhibition of herpes simplex virus (HSV) replication in cultured cells, effects on the synthesis of HSV DNA in isolated nuclei in vitro, as well as on DNA synthesis by purified HSV DNA polymerase. Distamycin A was the most active compound in all three antiviral tests, as well as the most toxic. However, several compounds, in particular the aromatic analogues 15 and 16, showed no toxicity under the experimental conditions used but were still very active in the three antiviral tests."}
{"id": "PMID:230358", "title": "A model of Martian surface chemistry.", "content": "Alkaline earth and alkali metal superoxides and peroxides, gamma-Fe2O3 and carbon suboxide polymer are proposed to be constituents of the Martian surface material. These reactive substances explain the water modified reactions and thermal behaviors of the Martian samples demonstrated by all of the Viking Biology Experiments. It is also proposed that the syntheses of these substances result mainly from electrical discharges between wind-mobilized particles at Martian pressures; plasmas are initiated and maintained by these discharges. Active species in the plasma either combine to form or react with inorganic surfaces to create the reactive constitutents.", "contents": "A model of Martian surface chemistry. Alkaline earth and alkali metal superoxides and peroxides, gamma-Fe2O3 and carbon suboxide polymer are proposed to be constituents of the Martian surface material. These reactive substances explain the water modified reactions and thermal behaviors of the Martian samples demonstrated by all of the Viking Biology Experiments. It is also proposed that the syntheses of these substances result mainly from electrical discharges between wind-mobilized particles at Martian pressures; plasmas are initiated and maintained by these discharges. Active species in the plasma either combine to form or react with inorganic surfaces to create the reactive constitutents."}
{"id": "PMID:230361", "title": "Sarcoid of the nervous system.", "content": "Sarcoid is a granulomatous disease of undetermined etiology characterized by the presence of epithelioid cell aggregates without caseation which proceeds to conversion to hyaline fibrous tissue or resolution. The sites of nervous system involvement include the meninges, cranial, and peripheral nerves, hypothalamus and pituitary gland, muscles, and, more rarely, brain and spinal cord parenchyma. In nervous system involvement there is usually cerebrospinal fluid lymphocytic pleocytosis and elevated protein but these findings are not specific. When other systems are involved with sarcoid the diagnosis of neurosarcoidosis is obvious. When an unusual neurological symptom complex presents, sarcoid should be considered. The author reviews the literature and presents 22 cases of sarcoid involvement of the nervous system.", "contents": "Sarcoid of the nervous system. Sarcoid is a granulomatous disease of undetermined etiology characterized by the presence of epithelioid cell aggregates without caseation which proceeds to conversion to hyaline fibrous tissue or resolution. The sites of nervous system involvement include the meninges, cranial, and peripheral nerves, hypothalamus and pituitary gland, muscles, and, more rarely, brain and spinal cord parenchyma. In nervous system involvement there is usually cerebrospinal fluid lymphocytic pleocytosis and elevated protein but these findings are not specific. When other systems are involved with sarcoid the diagnosis of neurosarcoidosis is obvious. When an unusual neurological symptom complex presents, sarcoid should be considered. The author reviews the literature and presents 22 cases of sarcoid involvement of the nervous system."}
{"id": "PMID:230363", "title": "Experimental infection of wildebeest with the herpesvirus of infectious bovine rhinotracheitis/infectious pustular vulvovaginitis.", "content": "Intravaginal inoculation of a wildebeest (Connochaetes taurinus) with a wildebeest strain of the infectious bovine rhinotracheitis/infectious pustular vulvovaginitis herpesvirus induced only mild vulvovaginitis. The same virus did not produce any disease in another wildebeest exposed intranasally. A wildebeest bull which was inoculated by preputial instillation developed mild posthitis. The virus was reisolated only from the sites of inoculation. A carrier state was initiated in a wildebeest inoculated only once, intravaginally. The presence of this virus in the various secretions is a potential source for venereal transmission.", "contents": "Experimental infection of wildebeest with the herpesvirus of infectious bovine rhinotracheitis/infectious pustular vulvovaginitis. Intravaginal inoculation of a wildebeest (Connochaetes taurinus) with a wildebeest strain of the infectious bovine rhinotracheitis/infectious pustular vulvovaginitis herpesvirus induced only mild vulvovaginitis. The same virus did not produce any disease in another wildebeest exposed intranasally. A wildebeest bull which was inoculated by preputial instillation developed mild posthitis. The virus was reisolated only from the sites of inoculation. A carrier state was initiated in a wildebeest inoculated only once, intravaginally. The presence of this virus in the various secretions is a potential source for venereal transmission."}
{"id": "PMID:230364", "title": "Powassan virus in Ixodes cookei and Mustelidae in New England.", "content": "Powassan virus was recovered from a pool of 3 nymphal and 1 adult female Ixodes cookei removed from a striped skunk (Mephitis mephitis) trapped in Massachusetts during 1967 and from a pool of 9 nymphal I. cookei from a long-tailed weasel (Mustela frenata) captured in Connecticut during 1978. Virus was detected in the blood of both mammals. Hemagglutination-inhibiting (HI) antibody to Powassan virus was demonstrated in 16.0% of the skunks sampled in Connecticut, and neutralizing antibody was detected in 83.3% of the skunks tested from Massachusetts. HI antibody was found in 1 of 6 long-tailed weasels from Connecticut and 1 of 6 short-tailed weasels (Mustela erminea) from Maine.", "contents": "Powassan virus in Ixodes cookei and Mustelidae in New England. Powassan virus was recovered from a pool of 3 nymphal and 1 adult female Ixodes cookei removed from a striped skunk (Mephitis mephitis) trapped in Massachusetts during 1967 and from a pool of 9 nymphal I. cookei from a long-tailed weasel (Mustela frenata) captured in Connecticut during 1978. Virus was detected in the blood of both mammals. Hemagglutination-inhibiting (HI) antibody to Powassan virus was demonstrated in 16.0% of the skunks sampled in Connecticut, and neutralizing antibody was detected in 83.3% of the skunks tested from Massachusetts. HI antibody was found in 1 of 6 long-tailed weasels from Connecticut and 1 of 6 short-tailed weasels (Mustela erminea) from Maine."}
{"id": "PMID:230365", "title": "Morphologic evidence of poxvirus in \"tattoo\" lesions from captive bottlenosed dolphins.", "content": "Skin lesions known as \"tattoos\", were observed in several captive Atlantic bottlenosed dolphins (tursiops truncatus) maintained at the Naval Ocean Systems Center, San Diego, California. Biopsy of typical lesions and subsequent ultrastructural examination revealed intracytoplasmic particles with poxvirus morphology.", "contents": "Morphologic evidence of poxvirus in \"tattoo\" lesions from captive bottlenosed dolphins. Skin lesions known as \"tattoos\", were observed in several captive Atlantic bottlenosed dolphins (tursiops truncatus) maintained at the Naval Ocean Systems Center, San Diego, California. Biopsy of typical lesions and subsequent ultrastructural examination revealed intracytoplasmic particles with poxvirus morphology."}
{"id": "PMID:230366", "title": "Pox infection among captive peacocks.", "content": "An outbreak of avian pox was detected among captive peacocks (Pavo cristatus) at Baghdad Zoological Park during spring, 1978. A total of 45 of the 60 birds in the aviary developed pox lesions around the beaks and eyes. Morbidity was 75% and mortality was 13%. A virus isolated from the skin lesions produced large plaques on the chorioallantoic membrane of developing chicken embryos and induced cytopathic effect characteristic for pox viruses in chicken embryo cell cultures. The virus neither haemagglutinated nor haemadsorbed to chicken erythrocytes. It was ether resistant and chloroform sensitive. Chickens inoculated with the virus by scarification developed localized pox-like lesions, while turkeys had only transient swelling of feather follicles at the site of inoculation. Virus partially purified with Genetron 113 was precipitated by antisera to fowlpox and pigeon pox viruses.", "contents": "Pox infection among captive peacocks. An outbreak of avian pox was detected among captive peacocks (Pavo cristatus) at Baghdad Zoological Park during spring, 1978. A total of 45 of the 60 birds in the aviary developed pox lesions around the beaks and eyes. Morbidity was 75% and mortality was 13%. A virus isolated from the skin lesions produced large plaques on the chorioallantoic membrane of developing chicken embryos and induced cytopathic effect characteristic for pox viruses in chicken embryo cell cultures. The virus neither haemagglutinated nor haemadsorbed to chicken erythrocytes. It was ether resistant and chloroform sensitive. Chickens inoculated with the virus by scarification developed localized pox-like lesions, while turkeys had only transient swelling of feather follicles at the site of inoculation. Virus partially purified with Genetron 113 was precipitated by antisera to fowlpox and pigeon pox viruses."}
{"id": "PMID:230367", "title": "Secondary myocardial disease. Virus myocarditis and cardiomyopathy.", "content": "In an attempt to prove the hypothesis that virus myocarditis may be a cause of idiopathic cardiomyopathy, clinical and experimental studies were performed. Eleven patients with a presumptive or proven diagnosis of virus myocarditis were followed for one and a half to 13 years after the acute illness. One patient died in the acute stage, six recovered completely and one continued to have bifascicular block without subjective symptoms. Three patients had exertional dyspnea, cardiomegaly and an abnormal ECG three to 13 years after the onset, and two of them had an enlarged LV cavity with reduced EF and histological changes in myocardial biopsies. The clinical picture in these three cases was similar to that seen in congestive cardiomyopathy. Clinical observations of the heart in an epidemic of coxsackie B 3 virus infection among school children revealed that 49 (19%) of 263 infected children had abnormal chest-X ray, electrocardiographic or echocardiographic findings one to 10 months after the onset, however none of them developed cardiomyopathy. In experimental infection of weanling golden hamsters with coxsackie B 3 virus (Nancy strain), all animals developed acute and severe myocarditis, and the virus was detected in the myocardium. Hemodynamic data suggested decreased contractility of the left ventricle in the acute stage. Histologically the heart showed focal myocardial necrosis and cellular infiltration without calcification, findings which resemble those in human doxsackie B virus myocarditi. Thus, the golden hamster is a better animal model than the mouse in studies on virus myocarditis and postcarditic cardiomyopathy.", "contents": "Secondary myocardial disease. Virus myocarditis and cardiomyopathy. In an attempt to prove the hypothesis that virus myocarditis may be a cause of idiopathic cardiomyopathy, clinical and experimental studies were performed. Eleven patients with a presumptive or proven diagnosis of virus myocarditis were followed for one and a half to 13 years after the acute illness. One patient died in the acute stage, six recovered completely and one continued to have bifascicular block without subjective symptoms. Three patients had exertional dyspnea, cardiomegaly and an abnormal ECG three to 13 years after the onset, and two of them had an enlarged LV cavity with reduced EF and histological changes in myocardial biopsies. The clinical picture in these three cases was similar to that seen in congestive cardiomyopathy. Clinical observations of the heart in an epidemic of coxsackie B 3 virus infection among school children revealed that 49 (19%) of 263 infected children had abnormal chest-X ray, electrocardiographic or echocardiographic findings one to 10 months after the onset, however none of them developed cardiomyopathy. In experimental infection of weanling golden hamsters with coxsackie B 3 virus (Nancy strain), all animals developed acute and severe myocarditis, and the virus was detected in the myocardium. Hemodynamic data suggested decreased contractility of the left ventricle in the acute stage. Histologically the heart showed focal myocardial necrosis and cellular infiltration without calcification, findings which resemble those in human doxsackie B virus myocarditi. Thus, the golden hamster is a better animal model than the mouse in studies on virus myocarditis and postcarditic cardiomyopathy."}
{"id": "PMID:230368", "title": "Experimental study of virus myocarditis in culture.", "content": "In this present paper, the authors would like to present here two points of results from the experimental study concerning virus myocarditis in culture. One is the direct delicate features of heart cells affected with Coxsackie B3 (Cox. B3) virus viewed through both light microscope and electron microscope. The other is the fact that marked proliferation of fibroblastic cells take place to replace the heart cells impaired by the virus suggesting to us the possibility of one of the genesisses, revealing fibroblastic involvement in the Idiopathic Cardiomyopathy (ICM) which could be followed by the residual of the virus myocarditis.", "contents": "Experimental study of virus myocarditis in culture. In this present paper, the authors would like to present here two points of results from the experimental study concerning virus myocarditis in culture. One is the direct delicate features of heart cells affected with Coxsackie B3 (Cox. B3) virus viewed through both light microscope and electron microscope. The other is the fact that marked proliferation of fibroblastic cells take place to replace the heart cells impaired by the virus suggesting to us the possibility of one of the genesisses, revealing fibroblastic involvement in the Idiopathic Cardiomyopathy (ICM) which could be followed by the residual of the virus myocarditis."}
{"id": "PMID:230369", "title": "Effects of coronary vasodilator on cyclic nucleotides. The concentrations of cyclic AMP and cyclic GMP in canine coronary artery and left ventricular muscle following the administration of various coronary vasodilators.", "content": "We examined the effects of various coronary vasodilator drugs, papaverine, dipyridamole, isosorbide dinitrate, amyl nitrite, nitroglycerin, diltiazem, and nifedipine, on cyclic nucleotides of the coronary artery and left ventricular muscle of anesthetized dogs at maximum coronary blood flow after the administration of each agents. Only papaverine and dipyridamole significantly increased the concentration of c-AMP in the coronary artery. Nitroglycerin and siosorbide dinitrate did not significantly change the concentration of c-AMP but rather increased the concentration of c-GMP. Coronary vasodilator drugs were divided into three groups in association with the relationship of cyclic nucleotides in the coronary artery. Group I, including papaverine, dipyridamole, and amyl nitrite, increased the concentration of c-AMP and the ratio of c-AMP to c-GMP. Group II, including nitroglycerin and isosorbide dinitrate, incrased the concentration of c-GMP and decreased the ratio of c-AMP to c-GMP. Group III, including nifedipine and diltiazem, had no effect on the cyclic nucleotides. Group I drugs also increased the concentration of c-AMP in the left ventricular muscle and so group I drugs may predispose the ischemic heart to develop ventricular arrhythmias. It seems that the most useful coronary vasodilator is no effect on the c-AMP in the ventricular muscle and group II and group III drugs are more useful coronary vasodilator drugs than group I drugs.", "contents": "Effects of coronary vasodilator on cyclic nucleotides. The concentrations of cyclic AMP and cyclic GMP in canine coronary artery and left ventricular muscle following the administration of various coronary vasodilators. We examined the effects of various coronary vasodilator drugs, papaverine, dipyridamole, isosorbide dinitrate, amyl nitrite, nitroglycerin, diltiazem, and nifedipine, on cyclic nucleotides of the coronary artery and left ventricular muscle of anesthetized dogs at maximum coronary blood flow after the administration of each agents. Only papaverine and dipyridamole significantly increased the concentration of c-AMP in the coronary artery. Nitroglycerin and siosorbide dinitrate did not significantly change the concentration of c-AMP but rather increased the concentration of c-GMP. Coronary vasodilator drugs were divided into three groups in association with the relationship of cyclic nucleotides in the coronary artery. Group I, including papaverine, dipyridamole, and amyl nitrite, increased the concentration of c-AMP and the ratio of c-AMP to c-GMP. Group II, including nitroglycerin and isosorbide dinitrate, incrased the concentration of c-GMP and decreased the ratio of c-AMP to c-GMP. Group III, including nifedipine and diltiazem, had no effect on the cyclic nucleotides. Group I drugs also increased the concentration of c-AMP in the left ventricular muscle and so group I drugs may predispose the ischemic heart to develop ventricular arrhythmias. It seems that the most useful coronary vasodilator is no effect on the c-AMP in the ventricular muscle and group II and group III drugs are more useful coronary vasodilator drugs than group I drugs."}
{"id": "PMID:230389", "title": "Detection of erythrocyte membrane structural abnormalities in lecithin: cholesterol acyltransferase deficiency using a spin label approach.", "content": "The membrane fluidity of erythrocytes from patients with Lecithin: cholesterol acyltransferase (LCAT) deficiency was studied by means of electron spin resonance. The temperature dependence of the separation of the outer extrema of the spectra of 2-(3-carboxy-propyl)-4,4-dimethyl, 2-tridecyl-3-oxazolidinyloxyl spin probe was monitored for normal, presumed carrier and clinically affected subjects. The temperature profile of controls was significantly different from that of the presumed carriers and the clinically affected individuals. The results show that the compositional abnormalities previously noted in erythrocyte membranes from patients with LCAT deficiency are associated with alterations in the physiocochemical state of the membrane. An investigation of the spectral lineshapes below 10 degrees C allowed a distinction to be made at the membrane level between clinically affected subjects and clinically normal heterozygous carriers. Alterations in the temperature dependence of elec-ron spin resonance parameters may provide a sensitive index of red cell membrane alterations in pathological states of generalized membrane involvement.", "contents": "Detection of erythrocyte membrane structural abnormalities in lecithin: cholesterol acyltransferase deficiency using a spin label approach. The membrane fluidity of erythrocytes from patients with Lecithin: cholesterol acyltransferase (LCAT) deficiency was studied by means of electron spin resonance. The temperature dependence of the separation of the outer extrema of the spectra of 2-(3-carboxy-propyl)-4,4-dimethyl, 2-tridecyl-3-oxazolidinyloxyl spin probe was monitored for normal, presumed carrier and clinically affected subjects. The temperature profile of controls was significantly different from that of the presumed carriers and the clinically affected individuals. The results show that the compositional abnormalities previously noted in erythrocyte membranes from patients with LCAT deficiency are associated with alterations in the physiocochemical state of the membrane. An investigation of the spectral lineshapes below 10 degrees C allowed a distinction to be made at the membrane level between clinically affected subjects and clinically normal heterozygous carriers. Alterations in the temperature dependence of elec-ron spin resonance parameters may provide a sensitive index of red cell membrane alterations in pathological states of generalized membrane involvement."}
{"id": "PMID:230390", "title": "Flow cytometry analysis of early DNA content changes in human and monkey cells following infection with Simian Virus 40.", "content": "Simian virus 40 (SV40) is capable of inducing cellular DNA synthesis in permissive and nonpermissive cells. Utilizing flow cytometry, we analyzed the DNA content changes in two diploid human cell strains and two monkey cell lines. The osteogenesis imperfecta (OI) human skin fibroblasts were induced into DNA synthesis, and within one to two cell generations, a polyploid cell population was produced. With WI-38 phase II cells, a similar pattern of increased cycling of cells into DNA synthesis was observed; however, the majority (approximately 60%) of the cells were blocked in the G2 + M phase of the cell cycle. At later time intervals, an increase in the G1 population was demonstrated. The two monkey cell lines responded to SV40 virus with an accumulation of cells in the G2 + M phase of the cell cycle. Thus, two diploid human cell strains exhibited different cell cycle kinetics early after infection with SV40 virus. The one strain (WI-38) behaved similarly to the two monkey cell lines studied. The other strain (OI) responded similarly to nonpermissive (transforming) cells infected with SV40 virus.", "contents": "Flow cytometry analysis of early DNA content changes in human and monkey cells following infection with Simian Virus 40. Simian virus 40 (SV40) is capable of inducing cellular DNA synthesis in permissive and nonpermissive cells. Utilizing flow cytometry, we analyzed the DNA content changes in two diploid human cell strains and two monkey cell lines. The osteogenesis imperfecta (OI) human skin fibroblasts were induced into DNA synthesis, and within one to two cell generations, a polyploid cell population was produced. With WI-38 phase II cells, a similar pattern of increased cycling of cells into DNA synthesis was observed; however, the majority (approximately 60%) of the cells were blocked in the G2 + M phase of the cell cycle. At later time intervals, an increase in the G1 population was demonstrated. The two monkey cell lines responded to SV40 virus with an accumulation of cells in the G2 + M phase of the cell cycle. Thus, two diploid human cell strains exhibited different cell cycle kinetics early after infection with SV40 virus. The one strain (WI-38) behaved similarly to the two monkey cell lines studied. The other strain (OI) responded similarly to nonpermissive (transforming) cells infected with SV40 virus."}
{"id": "PMID:230391", "title": "Endogenous cyclic AMP does not modulate transport of hexoses, nucleosides, or nucleobases in Chinese hamster ovary cells.", "content": "In a previous study we have demonstrated that neither extracellular nor intracellular cyclic adenosine monophosphate (AMP) levels directly affect the uptake of nucleosides, nucleobases, or hexoses by various types of cultured mammalian cells. Uptake of these nutrients into cells, however, involves two processes operating in tandem: facilitated transport across the membrane and intracellular phosphorylation; and uptake rates generally reflect the rates of substrate phosphorylation rather than of transport. In the present study we have examined the question of whether substrate transport per se is regulated by intracellular cyclic AMP. Initially various cell lines, grown both in suspension and monolayer culture, were screened for their cyclic AMP response to prostaglandin E1, isoproterenol, and inhibitors of cyclic AMP phosphodiesterase. Prostaglandin E1 treatment of Chinese hamster ovary cells was selected as the system giving the largest and most consistent (50-fold to 100-fold) elevation of cyclic AMP. Rapid kinetic techniques were used to measure the transport of 3-O-methylglucose, thymidine, adenosine, hypoxanthine, and adenine in wild-type cells and in mutant sublines incapable of phosphorylating these substrates. In no case was an increase in intracellular cyclic AMP accompanied by a significant change in the rate of transport of these substrates, although prostaglandin E1 slightly inhibited the transport of various substrates.", "contents": "Endogenous cyclic AMP does not modulate transport of hexoses, nucleosides, or nucleobases in Chinese hamster ovary cells. In a previous study we have demonstrated that neither extracellular nor intracellular cyclic adenosine monophosphate (AMP) levels directly affect the uptake of nucleosides, nucleobases, or hexoses by various types of cultured mammalian cells. Uptake of these nutrients into cells, however, involves two processes operating in tandem: facilitated transport across the membrane and intracellular phosphorylation; and uptake rates generally reflect the rates of substrate phosphorylation rather than of transport. In the present study we have examined the question of whether substrate transport per se is regulated by intracellular cyclic AMP. Initially various cell lines, grown both in suspension and monolayer culture, were screened for their cyclic AMP response to prostaglandin E1, isoproterenol, and inhibitors of cyclic AMP phosphodiesterase. Prostaglandin E1 treatment of Chinese hamster ovary cells was selected as the system giving the largest and most consistent (50-fold to 100-fold) elevation of cyclic AMP. Rapid kinetic techniques were used to measure the transport of 3-O-methylglucose, thymidine, adenosine, hypoxanthine, and adenine in wild-type cells and in mutant sublines incapable of phosphorylating these substrates. In no case was an increase in intracellular cyclic AMP accompanied by a significant change in the rate of transport of these substrates, although prostaglandin E1 slightly inhibited the transport of various substrates."}
{"id": "PMID:230392", "title": "Colorectal carcinoma 15 years after the diagnosis of perianal Paget disease.", "content": "We report a patient with perianal Paget disease who developed a colorectal carcinoma fifteen years later, complicated by pseudomyxoma peritoneal. While perianal Paget disease is often associated with underlying carcinomas noted at the time of the diagnosis, we suggest that perianal Paget disease may also predispose to the future development of colorectal cancer.", "contents": "Colorectal carcinoma 15 years after the diagnosis of perianal Paget disease. We report a patient with perianal Paget disease who developed a colorectal carcinoma fifteen years later, complicated by pseudomyxoma peritoneal. While perianal Paget disease is often associated with underlying carcinomas noted at the time of the diagnosis, we suggest that perianal Paget disease may also predispose to the future development of colorectal cancer."}
{"id": "PMID:230397", "title": "Pontine gigantocellular field neuron activity time-locked with the PGO waves in the transitional phase of sleep in the cat.", "content": "The extracellularly recorded discharge of pontine gigantocellular tegmental field (FTG) neurons was studied in the cat during the transitional phase of sleep (TPS), which signifies in this study the shift from slow wave sleep (S) to paradoxical sleep (PS). The first appearance of pontogeniculo-occipital (PGO) waves, which were led off from the lateral geniculate nucleus, indicated the start, and the decrease of neck muscle tone the end of TPS. TPS was chosen because most PGO waves were then isolated and thus suitable for comparison with the discharge of neurons, which were localized to the antero-lateral part of the FTG. In order to analyze the possible role of these neurons in the control of PGO wave activity, the mean discharge rate of FTG neurons was studied in greater detail during 200 ms periods before and after the onset of each isolated PGO wave. Most FTG neurons discharged phasically and their activity was closely related to isolated PGO waves, so that the highest rate of unit discharge occurred within 40 ms period after the onset of the isolated PGO wave, being time-locked with its first deflection.", "contents": "Pontine gigantocellular field neuron activity time-locked with the PGO waves in the transitional phase of sleep in the cat. The extracellularly recorded discharge of pontine gigantocellular tegmental field (FTG) neurons was studied in the cat during the transitional phase of sleep (TPS), which signifies in this study the shift from slow wave sleep (S) to paradoxical sleep (PS). The first appearance of pontogeniculo-occipital (PGO) waves, which were led off from the lateral geniculate nucleus, indicated the start, and the decrease of neck muscle tone the end of TPS. TPS was chosen because most PGO waves were then isolated and thus suitable for comparison with the discharge of neurons, which were localized to the antero-lateral part of the FTG. In order to analyze the possible role of these neurons in the control of PGO wave activity, the mean discharge rate of FTG neurons was studied in greater detail during 200 ms periods before and after the onset of each isolated PGO wave. Most FTG neurons discharged phasically and their activity was closely related to isolated PGO waves, so that the highest rate of unit discharge occurred within 40 ms period after the onset of the isolated PGO wave, being time-locked with its first deflection."}
{"id": "PMID:230405", "title": "Urinary cyclic AMP and cyclic GMP in normal and asthmatic subjects during exercise.", "content": "The purpose of this study was to compare exercise-induced changes in urinary cyclic AMP and cyclic GMP of normal and asthmatic subjects. All subjects were exercised to 80% of predicted maximum heart rate for 15 minutes on a bicycle ergometer. FEV1 was measured before and after exercise to determine the degree of bronchoconstriction due to exercise. Five urine specimens were collected by voluntary voiding at 20 minute intervals (one specimen before exercise and four after exercise). Before exercise, the asthmatic subjects excreted less cyclic GMP (p less than 0.05) but the same cyclic AMP as the normal subjects. Creatinine excretion in nine asthmatic subjects decreased by 24% (p less than 0.01) during exercise. In sixteen normal subjects (post-exercise bronchoconstriction less than 10%) cyclic AMP excretion increased by 19% (p less than 0.05) within 20 minutes after exercise, while cyclic GMP excretion did not change significantly. In thirteen asthmatic subjects (post-exercise bronchoconstriction greater than 20%) cyclic AMP excretion did not change significantly, while cyclic GMP excretion increased by 23% (p less than 0.05) within 20 minutes after exercise. This study has shown that exercise affects the excretion of cyclic AMP, cyclic GMP, and creatinine in normal and asthmatic subjects. The response of normal and asthmatic groups to exercise was the same for creatinine but different for cyclic AMP and cyclic GMP.", "contents": "Urinary cyclic AMP and cyclic GMP in normal and asthmatic subjects during exercise. The purpose of this study was to compare exercise-induced changes in urinary cyclic AMP and cyclic GMP of normal and asthmatic subjects. All subjects were exercised to 80% of predicted maximum heart rate for 15 minutes on a bicycle ergometer. FEV1 was measured before and after exercise to determine the degree of bronchoconstriction due to exercise. Five urine specimens were collected by voluntary voiding at 20 minute intervals (one specimen before exercise and four after exercise). Before exercise, the asthmatic subjects excreted less cyclic GMP (p less than 0.05) but the same cyclic AMP as the normal subjects. Creatinine excretion in nine asthmatic subjects decreased by 24% (p less than 0.01) during exercise. In sixteen normal subjects (post-exercise bronchoconstriction less than 10%) cyclic AMP excretion increased by 19% (p less than 0.05) within 20 minutes after exercise, while cyclic GMP excretion did not change significantly. In thirteen asthmatic subjects (post-exercise bronchoconstriction greater than 20%) cyclic AMP excretion did not change significantly, while cyclic GMP excretion increased by 23% (p less than 0.05) within 20 minutes after exercise. This study has shown that exercise affects the excretion of cyclic AMP, cyclic GMP, and creatinine in normal and asthmatic subjects. The response of normal and asthmatic groups to exercise was the same for creatinine but different for cyclic AMP and cyclic GMP."}
{"id": "PMID:230407", "title": "Involvement of cyclic AMP and its receptor protein in the sensitivity of Escherichia coli K 12 toward serine: excretion of 2-ketobutyrate, a precursor of isoleucine.", "content": "A relationship between serine-induced growth sensitivity and the cAMP-CAP complex is established. Mutants of Escherichia coli K 12 deficient either in the cya or crp gene function exhibit a resistant phenotype on serine media although they harbor a relA allele normally leading to sensitivity toward serine. The presence of a crp allele in a cya delta relA background restores the sensitivity phenotype, while the analysis of serine resistant mutants selected from a crp cya delta relA strain shows that the mutation leading to resistance is located at, or very near, the crp gene, giving a more or less Crp- phenotype. In addition crp cya delta relA strains excrete large quantities of 2-ketobutyrate when grown on glucose M63 medium. This excretion is unambiguously linked to the presence of the crp allele and is correlated with an enhanced threonine deaminase activity. Besides, the complex regulation exerted on the acetolactate synthase activities is discussed.", "contents": "Involvement of cyclic AMP and its receptor protein in the sensitivity of Escherichia coli K 12 toward serine: excretion of 2-ketobutyrate, a precursor of isoleucine. A relationship between serine-induced growth sensitivity and the cAMP-CAP complex is established. Mutants of Escherichia coli K 12 deficient either in the cya or crp gene function exhibit a resistant phenotype on serine media although they harbor a relA allele normally leading to sensitivity toward serine. The presence of a crp allele in a cya delta relA background restores the sensitivity phenotype, while the analysis of serine resistant mutants selected from a crp cya delta relA strain shows that the mutation leading to resistance is located at, or very near, the crp gene, giving a more or less Crp- phenotype. In addition crp cya delta relA strains excrete large quantities of 2-ketobutyrate when grown on glucose M63 medium. This excretion is unambiguously linked to the presence of the crp allele and is correlated with an enhanced threonine deaminase activity. Besides, the complex regulation exerted on the acetolactate synthase activities is discussed."}
{"id": "PMID:230408", "title": "The stimulation of Escherichia coli stringent factor-dependent synthesis of guanosine 3',5'-polyphosphate [(p)ppGpp] by rat liver ribosomal proteins.", "content": "The effect of groups of proteins from rat liver ribosomes on the Escherichia coli stringent factor-catalyzed synthesis of (p)ppGpp was tested. Most groups were capable of supporting (p)ppGpp synthesis; the exceptions were A40, B140, B240 and B160 which contain proteins which are relatively less basic than those in the active groups. The capacity of 30 individual rat liver ribosomal proteins to activate stringent factor was assessed; most sustained the synthesis of (p)ppGpp. Proteins S12, S21, L12, P1, and P2 (which are acidic or relatively acid) had no activity; proteins S6, S8, and L3 were the most active: the others had moderate activity.", "contents": "The stimulation of Escherichia coli stringent factor-dependent synthesis of guanosine 3',5'-polyphosphate [(p)ppGpp] by rat liver ribosomal proteins. The effect of groups of proteins from rat liver ribosomes on the Escherichia coli stringent factor-catalyzed synthesis of (p)ppGpp was tested. Most groups were capable of supporting (p)ppGpp synthesis; the exceptions were A40, B140, B240 and B160 which contain proteins which are relatively less basic than those in the active groups. The capacity of 30 individual rat liver ribosomal proteins to activate stringent factor was assessed; most sustained the synthesis of (p)ppGpp. Proteins S12, S21, L12, P1, and P2 (which are acidic or relatively acid) had no activity; proteins S6, S8, and L3 were the most active: the others had moderate activity."}
{"id": "PMID:230409", "title": "Control of minicell producing cell division by cAMP-receptor protein complex in Escherichia coli.", "content": "It has been established that the strain CA8000 of Escherichia coli K12 produces minicells. This phenotype of CA8000 has been shown to be suppressed by additional mutations in cya or crp genes. Minicell production by cya+ crp+ min bacteria is probably a consequence of error, introduced by horizontal growth, in the selection of site on the envelope for initiation of hemispherical growth.", "contents": "Control of minicell producing cell division by cAMP-receptor protein complex in Escherichia coli. It has been established that the strain CA8000 of Escherichia coli K12 produces minicells. This phenotype of CA8000 has been shown to be suppressed by additional mutations in cya or crp genes. Minicell production by cya+ crp+ min bacteria is probably a consequence of error, introduced by horizontal growth, in the selection of site on the envelope for initiation of hemispherical growth."}
{"id": "PMID:230410", "title": "A possible role of estrogens in carcinogenesis of non-target tissues.", "content": "The mitogenic action of the estrogen-receptor complex is supposedly similar in both normal and malignant target tissues. As receptors are present in several types of non-target tissues, in the case of lesions at the nuclear acceptor sites, the complex in those might be able to cause successive mitoses. Estrogen-dependent tumors of non-target tissues have been reported by several investigators. In normal and malignant cells of the breast and some other types of non-endocrine cells, the ability to produce their own estrogens (from circulating precursors) has been shown. The locally formed estrogens might have a role in the initiation of some malignant transformations. Indications of this process are the switching to estrogen production of some neoplastic endocrine or undifferentiated cells, certain ectopic effects displayed by some cancerous tissues, and the possible roles of GH, PRL and cholesterol in the development of some malignancies. The present endocrine system for the synthesis of the sexual hormones might be a specialization of a system at the cellular level. Polypeptide hormones might evolve from regulatory parts of cyclases or phosphodiesterases. Traces of the original biological processes might still be maintained by several cell-types.", "contents": "A possible role of estrogens in carcinogenesis of non-target tissues. The mitogenic action of the estrogen-receptor complex is supposedly similar in both normal and malignant target tissues. As receptors are present in several types of non-target tissues, in the case of lesions at the nuclear acceptor sites, the complex in those might be able to cause successive mitoses. Estrogen-dependent tumors of non-target tissues have been reported by several investigators. In normal and malignant cells of the breast and some other types of non-endocrine cells, the ability to produce their own estrogens (from circulating precursors) has been shown. The locally formed estrogens might have a role in the initiation of some malignant transformations. Indications of this process are the switching to estrogen production of some neoplastic endocrine or undifferentiated cells, certain ectopic effects displayed by some cancerous tissues, and the possible roles of GH, PRL and cholesterol in the development of some malignancies. The present endocrine system for the synthesis of the sexual hormones might be a specialization of a system at the cellular level. Polypeptide hormones might evolve from regulatory parts of cyclases or phosphodiesterases. Traces of the original biological processes might still be maintained by several cell-types."}
{"id": "PMID:230411", "title": "Metabolic effects of oral contraceptives containing 30 micrograms and 50 micrograms of oestrogen.", "content": "In Study A, biochemical data from 17 women who were not taking oral contraceptives were compared with those from women taking preparations which contained either 30 microgram of ethinyl oestradiol and 150 microgram of D-norgestrel (18 women) or 50 microgram of ethinyl oestradiol and 250 microgram of D-norgestrel (nine women). In Study B, biochemical data were collected from eight women before and during the first three or four months therapy with preparations containing 30 microgram of ethinyl oestradiol and 150 microgram of D-norgestrel. The two oral contraceptive dosage forms studied produced qualitatively and quantitatively similar metabolic changes. Both caused an increase in serum concentration of triglycerides (30% to 33%), beta-lipoproteins (27% to 29%) and ceruloplasmin (75% to 90%), and a decrease in serum levels of antithrombin III (22% to 29%) and ascorbic acid (30% to 42%). Serum cholesterol and phospholipid concentrations were unchanged. However, the proportion of serum cholesterol carried by alpha-lipoproteins (high density lipoproteins) decreased, while that carried by beta-lipoproteins (low density and very low density lipoproteins) increased. The former change is in the same direction, but much smaller than that observed in coronary heart disease.", "contents": "Metabolic effects of oral contraceptives containing 30 micrograms and 50 micrograms of oestrogen. In Study A, biochemical data from 17 women who were not taking oral contraceptives were compared with those from women taking preparations which contained either 30 microgram of ethinyl oestradiol and 150 microgram of D-norgestrel (18 women) or 50 microgram of ethinyl oestradiol and 250 microgram of D-norgestrel (nine women). In Study B, biochemical data were collected from eight women before and during the first three or four months therapy with preparations containing 30 microgram of ethinyl oestradiol and 150 microgram of D-norgestrel. The two oral contraceptive dosage forms studied produced qualitatively and quantitatively similar metabolic changes. Both caused an increase in serum concentration of triglycerides (30% to 33%), beta-lipoproteins (27% to 29%) and ceruloplasmin (75% to 90%), and a decrease in serum levels of antithrombin III (22% to 29%) and ascorbic acid (30% to 42%). Serum cholesterol and phospholipid concentrations were unchanged. However, the proportion of serum cholesterol carried by alpha-lipoproteins (high density lipoproteins) decreased, while that carried by beta-lipoproteins (low density and very low density lipoproteins) increased. The former change is in the same direction, but much smaller than that observed in coronary heart disease."}
{"id": "PMID:230415", "title": "[The problems of lipid metabolism. Demands for diagnostically improved insight into the function of lipoproteins (author's transl)].", "content": "In the course of a follow-up of 87 subjects with known hyperlipoproteinemia a new, simplified method was tested for quantification of the individual lipoprotein fractions capable of being performed by every larger laboratory, in contrast to the expensive ultracentrifugation. The LDL/HDL ratio proved to be the conclusive parameter for daily diagnosis in hospital and general practise. This enabled the most important aspects of the lipid metabolic situation of a patient to be recognized immediately.", "contents": "[The problems of lipid metabolism. Demands for diagnostically improved insight into the function of lipoproteins (author's transl)]. In the course of a follow-up of 87 subjects with known hyperlipoproteinemia a new, simplified method was tested for quantification of the individual lipoprotein fractions capable of being performed by every larger laboratory, in contrast to the expensive ultracentrifugation. The LDL/HDL ratio proved to be the conclusive parameter for daily diagnosis in hospital and general practise. This enabled the most important aspects of the lipid metabolic situation of a patient to be recognized immediately."}
{"id": "PMID:230417", "title": "Effects of dipyridamole in vivo on ATP and cAMP content in platelets and arterial walls and on atherosclerotic plaque formation.", "content": "In rabbits receiving an atherogenic diet for 2 months, the ATP content of platelet rich plasma (PRP) and arterial tissue was significantly elevated as compared to normal rabbits. This increase in ATP levels of platelets from atherosclerotic rabbits was paralleled by higher basal as well as PGI2-induced cAMP levels. In arterial tissues, an increase was only obtained in PGI2-stimulated cAMP content. Treatment with dipyridamole (DPD) for 4 weeks resulted in a reduction of the ATP content in platelets and arterial tissue from atherosclerotic rabbits to values seen in normal animals. Again, the reduction of ATP content was reflected in a decrease of basal as well as PGI2-induced cAMP levels in platelets, whereas in arterial tissue a decrease was only obtained in PGI2-induced cAMP content. At the same time, DPD treatment enhanced atherosclerotic plaque formation in the aortic wall. The enhanced atherosclerotic plaque formation seen in DPD treated atherosclerotic rabbits may be linked to the inhibition of adenosine uptake, resulting in a decrease of the adenine nucleotide pools of arterial wa-l cells. The decrease also caused a reduction in PGI2-induced cAMP content. This effect may be linked to altered proliferative activity, since in many cell types, stimulation of cAMP levels results in reduced proliferation rates.", "contents": "Effects of dipyridamole in vivo on ATP and cAMP content in platelets and arterial walls and on atherosclerotic plaque formation. In rabbits receiving an atherogenic diet for 2 months, the ATP content of platelet rich plasma (PRP) and arterial tissue was significantly elevated as compared to normal rabbits. This increase in ATP levels of platelets from atherosclerotic rabbits was paralleled by higher basal as well as PGI2-induced cAMP levels. In arterial tissues, an increase was only obtained in PGI2-stimulated cAMP content. Treatment with dipyridamole (DPD) for 4 weeks resulted in a reduction of the ATP content in platelets and arterial tissue from atherosclerotic rabbits to values seen in normal animals. Again, the reduction of ATP content was reflected in a decrease of basal as well as PGI2-induced cAMP levels in platelets, whereas in arterial tissue a decrease was only obtained in PGI2-induced cAMP content. At the same time, DPD treatment enhanced atherosclerotic plaque formation in the aortic wall. The enhanced atherosclerotic plaque formation seen in DPD treated atherosclerotic rabbits may be linked to the inhibition of adenosine uptake, resulting in a decrease of the adenine nucleotide pools of arterial wa-l cells. The decrease also caused a reduction in PGI2-induced cAMP content. This effect may be linked to altered proliferative activity, since in many cell types, stimulation of cAMP levels results in reduced proliferation rates."}
{"id": "PMID:230418", "title": "Interaction of diazepam with synaptic transmission in the in vitro rat hippocampus.", "content": "Diazepam (5 x 10(-8) - 10(-6) M) was found to augment recurrent inhibition of pyramidal neuron firing in a dose-dependent manner in rat hippocampal slices. To determine possible loci of this effect, diazepam was locally administered by pressure ejection from a micropipette, while recording action potentials from single inhibitory (\"basket\") interneurons. Diazepam induced reversible and reliable increases in interneuron firing in response to stimulation of Schaffer collateral and commissural afferents. Taken together with previous electrophysiological reports, these data suggest that benzodiazepines may augment central inhibition by increasing either the excitability of inhibitory interneurons, or by increasing the strength of excitatory afferents to these cells.", "contents": "Interaction of diazepam with synaptic transmission in the in vitro rat hippocampus. Diazepam (5 x 10(-8) - 10(-6) M) was found to augment recurrent inhibition of pyramidal neuron firing in a dose-dependent manner in rat hippocampal slices. To determine possible loci of this effect, diazepam was locally administered by pressure ejection from a micropipette, while recording action potentials from single inhibitory (\"basket\") interneurons. Diazepam induced reversible and reliable increases in interneuron firing in response to stimulation of Schaffer collateral and commissural afferents. Taken together with previous electrophysiological reports, these data suggest that benzodiazepines may augment central inhibition by increasing either the excitability of inhibitory interneurons, or by increasing the strength of excitatory afferents to these cells."}
{"id": "PMID:230419", "title": "Increased susceptibility of leukemia-infected chickens to Marek's disease.", "content": "Intramuscular (i.m.) injection of RAV-49 into 1--3 day-old chickens infected with Marek's disease herpes virus (MDHV) by contact led to exceedingly high rate of Marek's disease (MD) incidence. According to the data obtained in three experiments 52 out of 108 (48.1%) chickens fell ill in this group. While in the group uninfected with RAV-49 but contactly infected with MDV-Kekava there were only 11 out of 102, (10.7%) incidences. Simultaneous inoculations of RAV-49 and MDV had no effect on MD morbidity. Increased susceptibility of i.m. RAV-49-infected and contactly MDV-infected chickens to MD was abolished by simultaneous inoculation of RAV-49 and herpes virus of turkeys (HVT).", "contents": "Increased susceptibility of leukemia-infected chickens to Marek's disease. Intramuscular (i.m.) injection of RAV-49 into 1--3 day-old chickens infected with Marek's disease herpes virus (MDHV) by contact led to exceedingly high rate of Marek's disease (MD) incidence. According to the data obtained in three experiments 52 out of 108 (48.1%) chickens fell ill in this group. While in the group uninfected with RAV-49 but contactly infected with MDV-Kekava there were only 11 out of 102, (10.7%) incidences. Simultaneous inoculations of RAV-49 and MDV had no effect on MD morbidity. Increased susceptibility of i.m. RAV-49-infected and contactly MDV-infected chickens to MD was abolished by simultaneous inoculation of RAV-49 and herpes virus of turkeys (HVT)."}
{"id": "PMID:230420", "title": "Studies of the leukemic cell associated antigen(s) in mice with myeloid leukemia (Graffi), using the immunoperoxidase techniques.", "content": "Thymus, spleen and lymph nodes from myeloid leukemic mice (Graffi) were examined by light and electron microscope using immunoperoxidase techniques. As immune sera autologous sera were applied. The percentage of the labeled leukemic cells ranged from 30 to 60. It was established that leukemic cell associated antigen(s) was located mainly on the plasma and nuclear membranes. Occasionally this antigen(s) was observed in some areas of the endoplasmic reticulum, on separate cytoplasmic vesicles, on the budding viruses and on the chromatin. In addition, weakly expressed antigen(s) was located in cytosol. The mature virus particles were not labeled with peroxidase.", "contents": "Studies of the leukemic cell associated antigen(s) in mice with myeloid leukemia (Graffi), using the immunoperoxidase techniques. Thymus, spleen and lymph nodes from myeloid leukemic mice (Graffi) were examined by light and electron microscope using immunoperoxidase techniques. As immune sera autologous sera were applied. The percentage of the labeled leukemic cells ranged from 30 to 60. It was established that leukemic cell associated antigen(s) was located mainly on the plasma and nuclear membranes. Occasionally this antigen(s) was observed in some areas of the endoplasmic reticulum, on separate cytoplasmic vesicles, on the budding viruses and on the chromatin. In addition, weakly expressed antigen(s) was located in cytosol. The mature virus particles were not labeled with peroxidase."}
{"id": "PMID:230421", "title": "Conditions for hormone-stimulated expression of endogenous C57Bl strain-associated mammary tumor virus genome.", "content": "Full MMTV-Y gene expression can occur in dexamethasone-insulin-prolactin-stimulated cell cultured derived from C57Bl/10 mammary adenocarcinomas induced by syncarcinogenic action of chemical carcinogens (dimethylbenzanthracene), and mammotropic hormones (estrogen and prolactin). The rate of the hormone-stimulated virus production, as determined by biochemical, immunological and electron microscopical methods, was comparable to the level of spontaneous MMTV production by cells of established mouse mammary cancer cultures (CCL-51 and Mm5mt/cl). On the contrary, no virus production has been detected in hormone-stimulated cultures derived from C57Bl/10 mammary tumors induced by chemical carcinogen alone (urethan).", "contents": "Conditions for hormone-stimulated expression of endogenous C57Bl strain-associated mammary tumor virus genome. Full MMTV-Y gene expression can occur in dexamethasone-insulin-prolactin-stimulated cell cultured derived from C57Bl/10 mammary adenocarcinomas induced by syncarcinogenic action of chemical carcinogens (dimethylbenzanthracene), and mammotropic hormones (estrogen and prolactin). The rate of the hormone-stimulated virus production, as determined by biochemical, immunological and electron microscopical methods, was comparable to the level of spontaneous MMTV production by cells of established mouse mammary cancer cultures (CCL-51 and Mm5mt/cl). On the contrary, no virus production has been detected in hormone-stimulated cultures derived from C57Bl/10 mammary tumors induced by chemical carcinogen alone (urethan)."}
{"id": "PMID:230422", "title": "Carcinoembryonic antigen (CEA) in patients with malignant and non-malignant diseases.", "content": "Serum carcinoembryonic antigen (CEA) concentration was found to be raised in 503 of 550 patients (91%) with bladder cancer, lymphoma of intestine, hepatocellular carcinoma, bronchogenic carcinoma, prostate cancer, cirrhosis of liver and bilharziasis. The degree of elevation was moderate in all patients except in 189 patients in whom values more than 20 ng/ml were recorded, of which 53 patients with bladder cancer and 118 patients with bilharziasis. The mean CEA value in the patients with cirrhosis in the non-tumorous liver was slightly higher than that in those without cirrhosis, but the difference did not reach statistical significance (P greater than 0.01). There was no correlation between serum CEA and alph-fetoprotein (AFP) levels in all patients except in patients with bladder carcinoma, hepatoma and bilharziasis.", "contents": "Carcinoembryonic antigen (CEA) in patients with malignant and non-malignant diseases. Serum carcinoembryonic antigen (CEA) concentration was found to be raised in 503 of 550 patients (91%) with bladder cancer, lymphoma of intestine, hepatocellular carcinoma, bronchogenic carcinoma, prostate cancer, cirrhosis of liver and bilharziasis. The degree of elevation was moderate in all patients except in 189 patients in whom values more than 20 ng/ml were recorded, of which 53 patients with bladder cancer and 118 patients with bilharziasis. The mean CEA value in the patients with cirrhosis in the non-tumorous liver was slightly higher than that in those without cirrhosis, but the difference did not reach statistical significance (P greater than 0.01). There was no correlation between serum CEA and alph-fetoprotein (AFP) levels in all patients except in patients with bladder carcinoma, hepatoma and bilharziasis."}
{"id": "PMID:230423", "title": "Compared localizations of prolactin-like and adrenocorticotropin immunoreactivities within the brain of the rat.", "content": "By an immunoperoxidase (PAP) technique, ACTH- and prolactin-like substances were detected in neurons of several hypothalamic nuclei in young and adult rats. Neurons in the arcuate and ventromedial nuclei were simultaneously both ACTH-like and PRL-like positive. Labelled fibres were followed to their fields of projections. Intensity of labelling was not influenced by experimental procedures known to change PRL and ACTH content of the pituitary. Colchicine enhanced labelling of perikarya while lowering that of fibres. The results support neuronal synthesis of hormonal ACTH and PRL related molecules and their involvement in the control of autonomic nerve functions.", "contents": "Compared localizations of prolactin-like and adrenocorticotropin immunoreactivities within the brain of the rat. By an immunoperoxidase (PAP) technique, ACTH- and prolactin-like substances were detected in neurons of several hypothalamic nuclei in young and adult rats. Neurons in the arcuate and ventromedial nuclei were simultaneously both ACTH-like and PRL-like positive. Labelled fibres were followed to their fields of projections. Intensity of labelling was not influenced by experimental procedures known to change PRL and ACTH content of the pituitary. Colchicine enhanced labelling of perikarya while lowering that of fibres. The results support neuronal synthesis of hormonal ACTH and PRL related molecules and their involvement in the control of autonomic nerve functions."}
{"id": "PMID:230424", "title": "Nelson's syndrome: one disease or two?", "content": "We present a case of Nelson's syndrome in which the clinical, radiographic, and surgical findings are indicative of a discrete microadenoma rather than of diffuse pituitary hyperplasia. Ultrastructural analysis reveals this to be the first example of a sparsely granulated lesion in Nelson's syndrome and only the second such adrenocorticotropic hormone-secreting tumor reported. Unfortunately, there do not seem to be any firm ultrastructural features that differentiate between hyperplasia and discrete adenoma. Separation of the two entities may be important in delineating the pathogenesis and treatment of Nelson's syndrome; these are discussed.", "contents": "Nelson's syndrome: one disease or two? We present a case of Nelson's syndrome in which the clinical, radiographic, and surgical findings are indicative of a discrete microadenoma rather than of diffuse pituitary hyperplasia. Ultrastructural analysis reveals this to be the first example of a sparsely granulated lesion in Nelson's syndrome and only the second such adrenocorticotropic hormone-secreting tumor reported. Unfortunately, there do not seem to be any firm ultrastructural features that differentiate between hyperplasia and discrete adenoma. Separation of the two entities may be important in delineating the pathogenesis and treatment of Nelson's syndrome; these are discussed."}
{"id": "PMID:230425", "title": "Serum cortisol abnormalities after craniocerebral trauma.", "content": "Serial estimations of serum cortisol were performed in 49 patients with craniocerebral trauma. Abnormalities of serum cortisol, including alterations in diurnal rhythm and elevations of serum cortisol level, occurred in 21 patients. The frequency and severity of the abnormalities correlated with the severity of the head injury, and there was a trend suggesting that middle fossa basal skull fractures predisposed to cortisol abnormalities. A further 6 patients were studied to assess the effects of exogenous dexamethasone, and in all patients there was suppression of elevated serum cortisol levels by the dexamethasone. The findings suggest that hypercortisolemia after head injury is related to an alteration rather than an abolition of the normal feedback mechanism. (Neurosurgery, 5: 559--565, 1979).", "contents": "Serum cortisol abnormalities after craniocerebral trauma. Serial estimations of serum cortisol were performed in 49 patients with craniocerebral trauma. Abnormalities of serum cortisol, including alterations in diurnal rhythm and elevations of serum cortisol level, occurred in 21 patients. The frequency and severity of the abnormalities correlated with the severity of the head injury, and there was a trend suggesting that middle fossa basal skull fractures predisposed to cortisol abnormalities. A further 6 patients were studied to assess the effects of exogenous dexamethasone, and in all patients there was suppression of elevated serum cortisol levels by the dexamethasone. The findings suggest that hypercortisolemia after head injury is related to an alteration rather than an abolition of the normal feedback mechanism. (Neurosurgery, 5: 559--565, 1979)."}
{"id": "PMID:230426", "title": "Use of metrizamide computerized tomographic cisternography in the evaluation of patients with malignant glioma for immunotherapy.", "content": "The communication between the subarachnoid space and the surgically created tumor cavity in glioma patients was evaluated by metrizamide cisternography. It was necessary to know the presence or absence of such a communication to determine the route of administration of autologous lymphocytes as a form of immunotherapy. The contrast injections were made either into the spinal subarachnoid space or directly into the tumor cavity. The presence of communication was demonstrated and followed by computerized tomographic (CT) scanning. The results were also corroborated by comparing the white cell counts in the fluid from the tumor cavity and the spinal subarachnoid space 24 hours after autologous lymphoid cell infusion. In only two of seven patients was a communication present. In the five patients without a communication, the blocks were at the tentorial hiatus (one patient), due to a nonpatent subarachnoid space over the cerebral convexity (two patients), and the result of adhesions at the pial margin of the tumor cavity (three patients). In addition, certain limitations in the use of computerized tomography in the evaluation of glioma patients are demonstrated. These problems include the effects of steroids on tumor size, the poor correlation between \"enhancement\" on CT scan and tumor recurrence, and the difficulty of differentiating metrizamide and hemorrhage by CT scan in the immediate postoperative period. (Neurosurgery, 5: 576--582, 1979).", "contents": "Use of metrizamide computerized tomographic cisternography in the evaluation of patients with malignant glioma for immunotherapy. The communication between the subarachnoid space and the surgically created tumor cavity in glioma patients was evaluated by metrizamide cisternography. It was necessary to know the presence or absence of such a communication to determine the route of administration of autologous lymphocytes as a form of immunotherapy. The contrast injections were made either into the spinal subarachnoid space or directly into the tumor cavity. The presence of communication was demonstrated and followed by computerized tomographic (CT) scanning. The results were also corroborated by comparing the white cell counts in the fluid from the tumor cavity and the spinal subarachnoid space 24 hours after autologous lymphoid cell infusion. In only two of seven patients was a communication present. In the five patients without a communication, the blocks were at the tentorial hiatus (one patient), due to a nonpatent subarachnoid space over the cerebral convexity (two patients), and the result of adhesions at the pial margin of the tumor cavity (three patients). In addition, certain limitations in the use of computerized tomography in the evaluation of glioma patients are demonstrated. These problems include the effects of steroids on tumor size, the poor correlation between \"enhancement\" on CT scan and tumor recurrence, and the difficulty of differentiating metrizamide and hemorrhage by CT scan in the immediate postoperative period. (Neurosurgery, 5: 576--582, 1979)."}
{"id": "PMID:230428", "title": "[Considerations on a series of malaria cases].", "content": "Stress is laid on the seriousness of malaria and the causes of its unusual clinical pictures. Results obtained in the evaluation of G-6-PD, PK, intracellular K and globular resistance, in addition to other parameters, suggest (as pointed out in the literature) that altered cell metabolism may be the primary cause of haemolysis. Attention is also drawn to the lengthy persistance of gametes after gametocidal management in some patients, and the risks that this involves.", "contents": "[Considerations on a series of malaria cases]. Stress is laid on the seriousness of malaria and the causes of its unusual clinical pictures. Results obtained in the evaluation of G-6-PD, PK, intracellular K and globular resistance, in addition to other parameters, suggest (as pointed out in the literature) that altered cell metabolism may be the primary cause of haemolysis. Attention is also drawn to the lengthy persistance of gametes after gametocidal management in some patients, and the risks that this involves."}
{"id": "PMID:230431", "title": "The role of coxsackie B viruses in heart disease in New Zealand.", "content": "Sera from 622 patients received in a 20-month period were examined for coxsackie B neutralising antibody to serotypes 1--6. Two hundred and thirty-four of the total 622 were patients with a cardiac symptomatology, and 388 formed a comparable group of non-cardiac cases. There were 141 (60 percent) seropositive patients in the cardiac group, 34 percent and 29 percent of which respectively had antibody to B4 and B2. The clinical data provided on these 141 patients indicated that 33 (23 percent) had acute myocarditis, and 59 (42 percent) had acute pericarditis; 41 (29 percent) were recorded as having acute pleurodynia or Bronholm disease while eight (6 percent) had other indications of cardiac disease. Amongst the cardiac patients the highest prevalence of seropositivity was found in the 20--39 age group and 67 percent of these were males.", "contents": "The role of coxsackie B viruses in heart disease in New Zealand. Sera from 622 patients received in a 20-month period were examined for coxsackie B neutralising antibody to serotypes 1--6. Two hundred and thirty-four of the total 622 were patients with a cardiac symptomatology, and 388 formed a comparable group of non-cardiac cases. There were 141 (60 percent) seropositive patients in the cardiac group, 34 percent and 29 percent of which respectively had antibody to B4 and B2. The clinical data provided on these 141 patients indicated that 33 (23 percent) had acute myocarditis, and 59 (42 percent) had acute pericarditis; 41 (29 percent) were recorded as having acute pleurodynia or Bronholm disease while eight (6 percent) had other indications of cardiac disease. Amongst the cardiac patients the highest prevalence of seropositivity was found in the 20--39 age group and 67 percent of these were males."}
{"id": "PMID:230433", "title": "[5-fluorouracil inhibits bacterial collagenase and the collagenolytic system of a human rhabdomyosarcoma].", "content": "Protease inhibitory activity of eight cytostatic drugs on 5 proteases was tested by applying an immunoelectrophoretic system, a rhabdomyosarcoma's collagenolytic activity was investigated and inhibition studies were performed. We found 5-fluorouracil stopping collagenolytic activity of clostridial origin and the enzyme released by the tumor. No other cytostatic drug showed protease inhibition. The collagenolysis of the rhabdomyosarcoma was examined for its origin. Negative inhibition studies with ethylene-diamine-tetraacetate make the leukocyte origin highly improbable so that one can suggest that the hydrolytic enzyme derived from the tumor. Our findings could contribute to characterize the enzyme released by the tumor. We  suggest its role as a mediator of invasion and metastasis and on the other hand we detected its relatively specific inhibitor, 5-fluorouracil, which could influence tumorous and normal growth, regeneration and the intermediary protein metabolism.", "contents": "[5-fluorouracil inhibits bacterial collagenase and the collagenolytic system of a human rhabdomyosarcoma]. Protease inhibitory activity of eight cytostatic drugs on 5 proteases was tested by applying an immunoelectrophoretic system, a rhabdomyosarcoma's collagenolytic activity was investigated and inhibition studies were performed. We found 5-fluorouracil stopping collagenolytic activity of clostridial origin and the enzyme released by the tumor. No other cytostatic drug showed protease inhibition. The collagenolysis of the rhabdomyosarcoma was examined for its origin. Negative inhibition studies with ethylene-diamine-tetraacetate make the leukocyte origin highly improbable so that one can suggest that the hydrolytic enzyme derived from the tumor. Our findings could contribute to characterize the enzyme released by the tumor. We  suggest its role as a mediator of invasion and metastasis and on the other hand we detected its relatively specific inhibitor, 5-fluorouracil, which could influence tumorous and normal growth, regeneration and the intermediary protein metabolism."}
{"id": "PMID:230434", "title": "[Pressing problems of after care of patients with cancers of the cervix and corpus uteri].", "content": "A modern and optimal follow-up treatment of patients with uterine cancer requires a detailed knowledge of this disease and its sequelae. Incidence and localisation of cervical and endometrial cancers as well as kind and incidence of therapeutical side effects are demonstrated in the cases of the Gynecological University Hospital of Freiburg, GFR. A study of the psychosexual situation 2--4 years after therapy of uterine cancer is reported. Actual state of social assurances for cancer patients in the German Federal Republic is pointed out. The dates allow to draw conclusions for the follow-up of individual cases.", "contents": "[Pressing problems of after care of patients with cancers of the cervix and corpus uteri]. A modern and optimal follow-up treatment of patients with uterine cancer requires a detailed knowledge of this disease and its sequelae. Incidence and localisation of cervical and endometrial cancers as well as kind and incidence of therapeutical side effects are demonstrated in the cases of the Gynecological University Hospital of Freiburg, GFR. A study of the psychosexual situation 2--4 years after therapy of uterine cancer is reported. Actual state of social assurances for cancer patients in the German Federal Republic is pointed out. The dates allow to draw conclusions for the follow-up of individual cases."}
{"id": "PMID:230435", "title": "[Familial Hodgkin's disease: a case report and review of the literature].", "content": "In a family of five sisters four developed malignant lymphomas. A case report is given together with a literature survey of familial Hodgkin's disease. The observations fit the hypothesis that for the development of Hodgkin's disease two requirements must be met: a genetically determined susceptibility as well as some causative agent.", "contents": "[Familial Hodgkin's disease: a case report and review of the literature]. In a family of five sisters four developed malignant lymphomas. A case report is given together with a literature survey of familial Hodgkin's disease. The observations fit the hypothesis that for the development of Hodgkin's disease two requirements must be met: a genetically determined susceptibility as well as some causative agent."}
{"id": "PMID:230436", "title": "[Enzyme induction by Epstein-Barr-virus-producing infection of lymphoblastoid cell lines].", "content": "By means of biological in vitro assay collagenolytic activity of normal peripheral lymphocytes was compared to that of EBV-infected lymphoblastoid cell lines: the EBV-producing P3HR1 cells and the non-productive Raji cells. While normal lymphocytes and Raji cells revealed only traces of activity, significantly increased (p less than 0.001) collagenolytic activity was detected in samples of P3HR1, the cell-free EBV-suspension alone showed no collagenolysis. The described enzymatic activity was fully inhibited by 0-phenanthroline and EDTA indicating collagenase action. As main explanations for the phenomenon we suggest the possibility of viral enzyme induction, increased release of protease and thirdly that EBV carries a gene for synthesis of a collagenase.", "contents": "[Enzyme induction by Epstein-Barr-virus-producing infection of lymphoblastoid cell lines]. By means of biological in vitro assay collagenolytic activity of normal peripheral lymphocytes was compared to that of EBV-infected lymphoblastoid cell lines: the EBV-producing P3HR1 cells and the non-productive Raji cells. While normal lymphocytes and Raji cells revealed only traces of activity, significantly increased (p less than 0.001) collagenolytic activity was detected in samples of P3HR1, the cell-free EBV-suspension alone showed no collagenolysis. The described enzymatic activity was fully inhibited by 0-phenanthroline and EDTA indicating collagenase action. As main explanations for the phenomenon we suggest the possibility of viral enzyme induction, increased release of protease and thirdly that EBV carries a gene for synthesis of a collagenase."}
{"id": "PMID:230437", "title": "[Cyclic nucleotide concentration changes in different tumors and therapeutic success through increasing the cAMP level].", "content": "Changes in the concentration of cyclic AMP as well as cyclic GMP were measured in different murine tumors and in human tumors of varying malignancy. The quotient of cAMP and cGMP seems to be an important parameter for the molecular-biological derangement. Because of the recently much discussed importance of cAMP and cGMP in the immune defence the changes in the concentration of both nucleotides were measured in the T-lymphocytes of tumor patients. Significant changes occurred in patients with malignant melanoma. Investigations of the stimulatibility of the cAMP and cGMP levels revealed a diminished activatibility of the cAMP level and a higher stimulatibility of the cGMP level in the T-lymphocytes of patients with malignant melanoma as compared with those of the controls. On the basis of the working hypothesis that there is a causal relationship between the deranged dualism of cAMP and cGMP in the T-lymphocytes and the failure of the immunological tumor cell defence, an increase in the cAMP level is offered as a possible therapy. Therapeutic results in tumor-bearing mice and first results in melanoma patients are discussed.", "contents": "[Cyclic nucleotide concentration changes in different tumors and therapeutic success through increasing the cAMP level]. Changes in the concentration of cyclic AMP as well as cyclic GMP were measured in different murine tumors and in human tumors of varying malignancy. The quotient of cAMP and cGMP seems to be an important parameter for the molecular-biological derangement. Because of the recently much discussed importance of cAMP and cGMP in the immune defence the changes in the concentration of both nucleotides were measured in the T-lymphocytes of tumor patients. Significant changes occurred in patients with malignant melanoma. Investigations of the stimulatibility of the cAMP and cGMP levels revealed a diminished activatibility of the cAMP level and a higher stimulatibility of the cGMP level in the T-lymphocytes of patients with malignant melanoma as compared with those of the controls. On the basis of the working hypothesis that there is a causal relationship between the deranged dualism of cAMP and cGMP in the T-lymphocytes and the failure of the immunological tumor cell defence, an increase in the cAMP level is offered as a possible therapy. Therapeutic results in tumor-bearing mice and first results in melanoma patients are discussed."}
{"id": "PMID:230438", "title": "Cranial nerve damage in patients after alpha (heavy)-particle radiation to the pituitary.", "content": "The records of 161 patients were reviewed to determine if radiation damage had occurred following cranial irradiation. All of these patients had received alpha-particle radiation to their pituitary glands during the period when this form of therapy was given for diabetic retinopathy. Extraocular muscle palsy developed in 11 of these patients, iridoplegia in six, and fifth nerve damage in six. All of the palsies developed within a short period following their irradiation, and a definite dose relationship was present. The dose rate was approximately 100 rads/min for all cases. Fractionation varied but it is known for all cases. The estimated doses to the third, fourth, fifth, and sixth cranial nerves was calculated at a saggital plane 13 to 15 mm from the pituitary by using computer-drawn dosimetry charts for the respective aperture size. The energetic alpha particles were produced by the 184-in synchrocyclotron at Berkeley, Calif. A dose relationship for radiation palsies was apparent.", "contents": "Cranial nerve damage in patients after alpha (heavy)-particle radiation to the pituitary. The records of 161 patients were reviewed to determine if radiation damage had occurred following cranial irradiation. All of these patients had received alpha-particle radiation to their pituitary glands during the period when this form of therapy was given for diabetic retinopathy. Extraocular muscle palsy developed in 11 of these patients, iridoplegia in six, and fifth nerve damage in six. All of the palsies developed within a short period following their irradiation, and a definite dose relationship was present. The dose rate was approximately 100 rads/min for all cases. Fractionation varied but it is known for all cases. The estimated doses to the third, fourth, fifth, and sixth cranial nerves was calculated at a saggital plane 13 to 15 mm from the pituitary by using computer-drawn dosimetry charts for the respective aperture size. The energetic alpha particles were produced by the 184-in synchrocyclotron at Berkeley, Calif. A dose relationship for radiation palsies was apparent."}
{"id": "PMID:230439", "title": "Aniridia caused by a heritable chromosome 11 deletion.", "content": "A child with aniridia, multiple anomalies, severe failure to thrive, and severe psychomotor retardation is shown to have a syndrome similar to, though more severe than, other patients with overlapping deletions of the short arm of chromosome 11 (Pediatrics 64:604, 1978). Her deletion (46,XX,del [11p] [pter yields p14::p11.3 yields qter]) was derived from her mother, who has a chromosome 11 shift (46,XX,der [11] [pter yields p14::p11.3 yields q22::p14 yields p11.3::q22 yields qter]). The significance of del (11p) in the aniridia-Wilms' tumor association is discussed, and the del (11p) basis for aniridia is compared with other genetic bases for aniridia.", "contents": "Aniridia caused by a heritable chromosome 11 deletion. A child with aniridia, multiple anomalies, severe failure to thrive, and severe psychomotor retardation is shown to have a syndrome similar to, though more severe than, other patients with overlapping deletions of the short arm of chromosome 11 (Pediatrics 64:604, 1978). Her deletion (46,XX,del [11p] [pter yields p14::p11.3 yields qter]) was derived from her mother, who has a chromosome 11 shift (46,XX,der [11] [pter yields p14::p11.3 yields q22::p14 yields p11.3::q22 yields qter]). The significance of del (11p) in the aniridia-Wilms' tumor association is discussed, and the del (11p) basis for aniridia is compared with other genetic bases for aniridia."}
{"id": "PMID:230442", "title": "[Human erythrocyte protein kinases (author's transl)].", "content": "Cyclic AMP dependent and independent protein kinase activities are present in membrane as well as cytosol of human erythrocyte. Red cell membrane contains at least: 1) a cAMP dependent histone kinase type I using ATP as phosphoryl donor; 2) a cAMP independent casein kinase using ATP or GTP as phosphoryl donor; this kinase probably phosphorylates erythrocyte spectrin. In lysate of human red cell there are two or three cAMP dependent protein kinase type I and II and one cAMP independent casein kinase. Characteristics of these protein kinase activities are reviewed. Membrane substrates are numbered taking in account that the activity assays are often of dubious value. Several phosphorylation abnormalities previously reported in hematologic and non-hematologic disorders are still uncertain and at present time not any red cell protein kinase deficiency has been demonstrated.", "contents": "[Human erythrocyte protein kinases (author's transl)]. Cyclic AMP dependent and independent protein kinase activities are present in membrane as well as cytosol of human erythrocyte. Red cell membrane contains at least: 1) a cAMP dependent histone kinase type I using ATP as phosphoryl donor; 2) a cAMP independent casein kinase using ATP or GTP as phosphoryl donor; this kinase probably phosphorylates erythrocyte spectrin. In lysate of human red cell there are two or three cAMP dependent protein kinase type I and II and one cAMP independent casein kinase. Characteristics of these protein kinase activities are reviewed. Membrane substrates are numbered taking in account that the activity assays are often of dubious value. Several phosphorylation abnormalities previously reported in hematologic and non-hematologic disorders are still uncertain and at present time not any red cell protein kinase deficiency has been demonstrated."}
{"id": "PMID:230443", "title": "An analysis of the peritonitis in acute murine reovirus infection.", "content": "Reovirus 3 replicates in the mesothelial cells of the peritoneal cavity of infected neonatal Prince Henry mice. As virus replication becomes evident in these cells lymphocytes, polymorphonuclear leucocytes and especially mononuclear phagocytes increase in number in the peritoneal exudate and often surround the exfoliated and degenerating infected mesothelial cells. These events are accompanied by a polymorphonuclear leucocytosis, a lymphopenia and a transient monocytosis which reverses to a monocytopenia as virus replication appears in a variety of organs. Although in the peritoneal cavity the majority of exuded monocytes ingest virions and cellular debris a small proportion supports replication of reovirus 3. Polymorphonuclear leucocytes, on the other hand, did not exhibit evidence of reovirus replication.", "contents": "An analysis of the peritonitis in acute murine reovirus infection. Reovirus 3 replicates in the mesothelial cells of the peritoneal cavity of infected neonatal Prince Henry mice. As virus replication becomes evident in these cells lymphocytes, polymorphonuclear leucocytes and especially mononuclear phagocytes increase in number in the peritoneal exudate and often surround the exfoliated and degenerating infected mesothelial cells. These events are accompanied by a polymorphonuclear leucocytosis, a lymphopenia and a transient monocytosis which reverses to a monocytopenia as virus replication appears in a variety of organs. Although in the peritoneal cavity the majority of exuded monocytes ingest virions and cellular debris a small proportion supports replication of reovirus 3. Polymorphonuclear leucocytes, on the other hand, did not exhibit evidence of reovirus replication."}
{"id": "PMID:230444", "title": "The pathological assessment of ovarian neoplasms. III: The malignant \"epithelial\" tumours.", "content": "One thousand common \"epithelial\" tumours of the ovary were encountered in a 25-yr study period at the King George V Memorial Hospital. These tumours were classified according to the World Health Organisation (W.H.O.) Histological Classification of Ovarian Tumours. In this report a detailed histological assessment of the 298 malignant \"epithelial\" tumours is presented, including criteria for histological grading and typing. Evidence for the multifocal tumorigenesis of serous tumours and the pathological correlates of endometrioid carcinoma are stressed.", "contents": "The pathological assessment of ovarian neoplasms. III: The malignant \"epithelial\" tumours. One thousand common \"epithelial\" tumours of the ovary were encountered in a 25-yr study period at the King George V Memorial Hospital. These tumours were classified according to the World Health Organisation (W.H.O.) Histological Classification of Ovarian Tumours. In this report a detailed histological assessment of the 298 malignant \"epithelial\" tumours is presented, including criteria for histological grading and typing. Evidence for the multifocal tumorigenesis of serous tumours and the pathological correlates of endometrioid carcinoma are stressed."}
{"id": "PMID:230447", "title": "Influence of aminophylline and cyclic AMP on glycogen metabolism in fetal rat lung in organ culture.", "content": "The glycogen content of fetal rat lung declines coincident with increased pulmonary phospholipid synthesis. Aminophylline, a methylxanthine cyclic adenosine 3',5' monophosphate (AMP) phosphodiesterase inhibitor, and cyclic AMP augment fetal lung phospholipid synthesis. Because lung glycogen breakdown may contribute to pulmonary phospholipid synthesis, the effects of aminophylline and cyclic AMP on glycogen metabolism were studied in explants of 19 day fetal rat lung in organ culture. Treatment with aminophylline or dibutyryl cyclic AMP for 24 hr, resulted in a 25% (P less than 0.025) and 75% (P less than 0.001) decrease, respectively, in the glycogen content of the explants. Glycogen synthase I activity was reduced by 32% in aminophylline treated cultures (P less than 0.025) and 25% in cyclic AMP treated cultures (P less than 0.025). The percent of total synthase in the active form was significantly reduced in all treated cultures. Neither aminophylline nor cyclic AMP treatment resulted in significant changes in glycogen phosphorylase a or total phosphorylase activity.", "contents": "Influence of aminophylline and cyclic AMP on glycogen metabolism in fetal rat lung in organ culture. The glycogen content of fetal rat lung declines coincident with increased pulmonary phospholipid synthesis. Aminophylline, a methylxanthine cyclic adenosine 3',5' monophosphate (AMP) phosphodiesterase inhibitor, and cyclic AMP augment fetal lung phospholipid synthesis. Because lung glycogen breakdown may contribute to pulmonary phospholipid synthesis, the effects of aminophylline and cyclic AMP on glycogen metabolism were studied in explants of 19 day fetal rat lung in organ culture. Treatment with aminophylline or dibutyryl cyclic AMP for 24 hr, resulted in a 25% (P less than 0.025) and 75% (P less than 0.001) decrease, respectively, in the glycogen content of the explants. Glycogen synthase I activity was reduced by 32% in aminophylline treated cultures (P less than 0.025) and 25% in cyclic AMP treated cultures (P less than 0.025). The percent of total synthase in the active form was significantly reduced in all treated cultures. Neither aminophylline nor cyclic AMP treatment resulted in significant changes in glycogen phosphorylase a or total phosphorylase activity."}
{"id": "PMID:230448", "title": "Hormonal phenotype and HLA-genotype in families of patients with congenital adrenal hyperplasia (21-hydroxylase deficiency).", "content": "The response of 17-hydroxyprogesterone (17-OHP) and cortisol (F) to a 6-hr ACTH stimulation in families of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency was studied. These studies demonstrated that siblings who should be heterozygous carriers of the 21-hydroxylase deficiency gene based on HLA genotyping are hormonally different from the general population. In pre- and early pubertal children predicted to be heterozygous carriers of the gene based on HLA genotyping, the 17-OHP level (13.1 +/- 4.5 ng/ml), the rate of increase of 17-OHP (0.03 +/- 0.01), and the ratio of 17-OHP/F at 6 hr (0.27 +/- 0.07) were significantly higher (P less than 0.001) than in the control population, (3.9 +/- 1.9, 0.009 +/- 0.005, and 0.08 +/- 0.04 ng/ml, respectively). In late and postpubertal males, these hormonal parameters in the heterozygotes (17 +/- 9.7, 0.04 +/- 0.026, 0.42 +/- 0.33 ng/ml, respectively) were significantly higher (P less than 0.001) than in the general population (5.3 +/- 1.6, 0.009 +/- 0.004, and 0.1 +/- 0.03 ng/ml, respectively). In postmenarchal females, the mean hormone responses in the heterozygotes (12.1 +/- 9.7, 0.03 +/- 0.02, and 0.27 +/- 0.24 ng/ml, respectively) were significantly higher (P less than 0.005, less than 0.01, less than 0.005, respectively) than in the general population (5.2 +/- 2.5, 0.01 +/- 0.007, and 0.1 +/- 0.04 ng/ml, respectively). However, the overlapping values did not permit a clear differentiation of the hormonal responses in these two groups. Another (ACTH) stimulation in one family demonstrated that a father of a patient probably is a previously unrecognized homozygous affected patient and,thus, revision of the congenital adrenal hyperplasia (CAH) genotype for this family was required.", "contents": "Hormonal phenotype and HLA-genotype in families of patients with congenital adrenal hyperplasia (21-hydroxylase deficiency). The response of 17-hydroxyprogesterone (17-OHP) and cortisol (F) to a 6-hr ACTH stimulation in families of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency was studied. These studies demonstrated that siblings who should be heterozygous carriers of the 21-hydroxylase deficiency gene based on HLA genotyping are hormonally different from the general population. In pre- and early pubertal children predicted to be heterozygous carriers of the gene based on HLA genotyping, the 17-OHP level (13.1 +/- 4.5 ng/ml), the rate of increase of 17-OHP (0.03 +/- 0.01), and the ratio of 17-OHP/F at 6 hr (0.27 +/- 0.07) were significantly higher (P less than 0.001) than in the control population, (3.9 +/- 1.9, 0.009 +/- 0.005, and 0.08 +/- 0.04 ng/ml, respectively). In late and postpubertal males, these hormonal parameters in the heterozygotes (17 +/- 9.7, 0.04 +/- 0.026, 0.42 +/- 0.33 ng/ml, respectively) were significantly higher (P less than 0.001) than in the general population (5.3 +/- 1.6, 0.009 +/- 0.004, and 0.1 +/- 0.03 ng/ml, respectively). In postmenarchal females, the mean hormone responses in the heterozygotes (12.1 +/- 9.7, 0.03 +/- 0.02, and 0.27 +/- 0.24 ng/ml, respectively) were significantly higher (P less than 0.005, less than 0.01, less than 0.005, respectively) than in the general population (5.2 +/- 2.5, 0.01 +/- 0.007, and 0.1 +/- 0.04 ng/ml, respectively). However, the overlapping values did not permit a clear differentiation of the hormonal responses in these two groups. Another (ACTH) stimulation in one family demonstrated that a father of a patient probably is a previously unrecognized homozygous affected patient and,thus, revision of the congenital adrenal hyperplasia (CAH) genotype for this family was required."}
{"id": "PMID:230449", "title": "Deficiency of glucose-6-phosphate dehydrogenase found in a case of hepatic fructose-1,6-diphosphatase deficiency.", "content": "The first case of fructose-1,6-diphosphatase (FDPase) deficiency in Japan showed a decreased activity of glucose-6-phosphate dehydrogenase (G6PD) in the liver, white, and red blood cells. In the enzymatic study of G6PD which was partially purified from red cells, the following characteristics were observed in the enzyme of the patient. 1) The G6PD activity of the patient was reduced to 17% of normal, but no evidence of a hemolytic episode was found in his past and family history. 2) In the investigation of G6PD of the patient, no abnormalities were observed in its enzymatic parameters such as electrophoretic mobility, Km for G6P and NADP, Ki for NADPH, the utilization of 2-deoxy G6P and deamino NADP, heat-stability, and pH curves. 3) The dissociation constants of red blood cell G6PD for NADP and NADPH, which were obtained from the investigations on the reactivation of cold-inactivated G6PD at 37 degrees C, were about 3 times higher in the patient as compared to the values of the normal controls. Based on these findings, it might be concluded that the G6PD deficiency found in the red blood cells of this case of a FDPase deficiency is a unique variant, which could not be characterized by using only the method recommended by a World Health Organization (WHO) scientific group. Considering that the abnormality observed in the G6PD of this patient was a decrease in the affinity of the enzyme for its coenzymes, the dissociation constants for the coenzymes in reactivation process might be another important kinetic parameter in characterizing the G6PD deficiency.", "contents": "Deficiency of glucose-6-phosphate dehydrogenase found in a case of hepatic fructose-1,6-diphosphatase deficiency. The first case of fructose-1,6-diphosphatase (FDPase) deficiency in Japan showed a decreased activity of glucose-6-phosphate dehydrogenase (G6PD) in the liver, white, and red blood cells. In the enzymatic study of G6PD which was partially purified from red cells, the following characteristics were observed in the enzyme of the patient. 1) The G6PD activity of the patient was reduced to 17% of normal, but no evidence of a hemolytic episode was found in his past and family history. 2) In the investigation of G6PD of the patient, no abnormalities were observed in its enzymatic parameters such as electrophoretic mobility, Km for G6P and NADP, Ki for NADPH, the utilization of 2-deoxy G6P and deamino NADP, heat-stability, and pH curves. 3) The dissociation constants of red blood cell G6PD for NADP and NADPH, which were obtained from the investigations on the reactivation of cold-inactivated G6PD at 37 degrees C, were about 3 times higher in the patient as compared to the values of the normal controls. Based on these findings, it might be concluded that the G6PD deficiency found in the red blood cells of this case of a FDPase deficiency is a unique variant, which could not be characterized by using only the method recommended by a World Health Organization (WHO) scientific group. Considering that the abnormality observed in the G6PD of this patient was a decrease in the affinity of the enzyme for its coenzymes, the dissociation constants for the coenzymes in reactivation process might be another important kinetic parameter in characterizing the G6PD deficiency."}
{"id": "PMID:230452", "title": "Role of the basal sodium intake in the rats on their response to a natriuretic factor.", "content": "A previously described natriuretic factor found in urine from man and dogs receiving a high salt diet has been postulated to be of hormonal nature. In order to test this hypothesis, natriuretic factor obtained from a pool of human urine of a standard activity has been injected into rats fed 0.55 (group A), 3.55 (group B), 6.55 (group C) mEq sodium a day as it has been shown that the endogenous activity of this factor depends on the sodium content of the diet. This material induces an increment of the UNaV and FENa in the rats averaging respectively 429.6 +/- 150.1% and 317.5 +/- 71.14% for the rats from group A, 103 +/- 29% and 99.7 +/- 26.25% for the rats from group B, 56.3 +/- 34.4% and 63.2 +/- 35.8% for the rats from group C reflecting the degree of statistical significance observed between the absolute values obtained during the control and experimental periods for each group. In addition, a dose-response curve has been established. Altogether the results suggest the hormonal nature of the natriuretic factor and design the kidney as the target organ. These data allow to define the best conditions under which the rats have to be in order to provide a valuable bioassay for this natriuretic material.", "contents": "Role of the basal sodium intake in the rats on their response to a natriuretic factor. A previously described natriuretic factor found in urine from man and dogs receiving a high salt diet has been postulated to be of hormonal nature. In order to test this hypothesis, natriuretic factor obtained from a pool of human urine of a standard activity has been injected into rats fed 0.55 (group A), 3.55 (group B), 6.55 (group C) mEq sodium a day as it has been shown that the endogenous activity of this factor depends on the sodium content of the diet. This material induces an increment of the UNaV and FENa in the rats averaging respectively 429.6 +/- 150.1% and 317.5 +/- 71.14% for the rats from group A, 103 +/- 29% and 99.7 +/- 26.25% for the rats from group B, 56.3 +/- 34.4% and 63.2 +/- 35.8% for the rats from group C reflecting the degree of statistical significance observed between the absolute values obtained during the control and experimental periods for each group. In addition, a dose-response curve has been established. Altogether the results suggest the hormonal nature of the natriuretic factor and design the kidney as the target organ. These data allow to define the best conditions under which the rats have to be in order to provide a valuable bioassay for this natriuretic material."}
{"id": "PMID:230453", "title": "Serotoninergic mechanisms of beta-endorphin-induced hypothermia in rats.", "content": "The effects of intraventricular administration of beta-endorphin on thermoregulatory responses of unanesthetized rats to different ambient temperatures (Ta) of 8, 22 and 30 degrees C were assessed. Administration of beta-endorphin produced a fall in rectal temperature at both Ta 8 and 22 degrees C. The hypothermia in response to beta-endorphin was brought about by both cutaneous vasodilation (as indicated by an increase in both the tail and the foot skin temperatures) and decreases in metabolic heat production. However, at Ta 30 degrees C, administration of beta-endorphin produced no change in rectal temperature or other thermoregulatory responses. Furthermore, the hypothermic effect induced by beta-endorphin was greatly attenuated by either the depletion of brain serotonin levels (with 5,6-dihydroxytryptamine and p-chlorophenylanine) or the blockade of opiate receptors (with naloxone). The data indicate that beta-endorphin leads to hypothermia in rats by increasing sensible heat loss and decreasing metabolic heat production, probably via the release of endogenous serotonin within brain.", "contents": "Serotoninergic mechanisms of beta-endorphin-induced hypothermia in rats. The effects of intraventricular administration of beta-endorphin on thermoregulatory responses of unanesthetized rats to different ambient temperatures (Ta) of 8, 22 and 30 degrees C were assessed. Administration of beta-endorphin produced a fall in rectal temperature at both Ta 8 and 22 degrees C. The hypothermia in response to beta-endorphin was brought about by both cutaneous vasodilation (as indicated by an increase in both the tail and the foot skin temperatures) and decreases in metabolic heat production. However, at Ta 30 degrees C, administration of beta-endorphin produced no change in rectal temperature or other thermoregulatory responses. Furthermore, the hypothermic effect induced by beta-endorphin was greatly attenuated by either the depletion of brain serotonin levels (with 5,6-dihydroxytryptamine and p-chlorophenylanine) or the blockade of opiate receptors (with naloxone). The data indicate that beta-endorphin leads to hypothermia in rats by increasing sensible heat loss and decreasing metabolic heat production, probably via the release of endogenous serotonin within brain."}
{"id": "PMID:230454", "title": "Description of the firing pattern of respiratory neurons by frequency modulated interspike interval distributions.", "content": "The description of the firing pattern of respiratory neurons presented here is based on extracellular recordings and directed to the possible influence (facilitating of inhibiting effect) that the neuron might have upon others (output) as well as to the extend of influences that are received from other neurons (input). Developing such a description the spike generating mechanism of the neuron was in a first approach characterized by a frequency modulated gamma distribution. Using this approach an acceptable match between calculated and measured interspike-interval distribution was found although mostly not statistically significant. This non-significancy is most probably due to the choice of the simple gamma distribution as a first approach. However, applying this description it seems possible to retrieve statistical information about the interaction between neurons from extracellular recordings. Based on this description it is proposed to use modal spike frequency as well as the variance of the interspike interval distribution as estimates for the activity and the extent of activation of the neuron.", "contents": "Description of the firing pattern of respiratory neurons by frequency modulated interspike interval distributions. The description of the firing pattern of respiratory neurons presented here is based on extracellular recordings and directed to the possible influence (facilitating of inhibiting effect) that the neuron might have upon others (output) as well as to the extend of influences that are received from other neurons (input). Developing such a description the spike generating mechanism of the neuron was in a first approach characterized by a frequency modulated gamma distribution. Using this approach an acceptable match between calculated and measured interspike-interval distribution was found although mostly not statistically significant. This non-significancy is most probably due to the choice of the simple gamma distribution as a first approach. However, applying this description it seems possible to retrieve statistical information about the interaction between neurons from extracellular recordings. Based on this description it is proposed to use modal spike frequency as well as the variance of the interspike interval distribution as estimates for the activity and the extent of activation of the neuron."}
{"id": "PMID:230455", "title": "The role of the adrenergic innervation to the pancreatic islets in the control of insulin release during exercise in man.", "content": "The normal depression of plasma insulin concentration during exercise has been ascribed to adrenergic inhibition of insulin release and the role of humoral catecholamines in this hormonal adjustment has repeatedly been stressed. In the present study this contention has been investigated in 6 bilaterally adrenalectomized patients and in 6 sex- and age-matched controls who undertook exercise on an ergometer until they were exhausted. No differences were observed in any cardiovascular or metabolic adjustments between the two groups during strenous exercise. Mean plasma insulin concentration fell by about 50% in both groups. Phentolamine effectively abolished the fall in plasma insulin concentration during exercise in 2 adrenalectomized patients. The results suggest that the adrenergic nerves that supply the B-cells have a functional role in man during exercise.", "contents": "The role of the adrenergic innervation to the pancreatic islets in the control of insulin release during exercise in man. The normal depression of plasma insulin concentration during exercise has been ascribed to adrenergic inhibition of insulin release and the role of humoral catecholamines in this hormonal adjustment has repeatedly been stressed. In the present study this contention has been investigated in 6 bilaterally adrenalectomized patients and in 6 sex- and age-matched controls who undertook exercise on an ergometer until they were exhausted. No differences were observed in any cardiovascular or metabolic adjustments between the two groups during strenous exercise. Mean plasma insulin concentration fell by about 50% in both groups. Phentolamine effectively abolished the fall in plasma insulin concentration during exercise in 2 adrenalectomized patients. The results suggest that the adrenergic nerves that supply the B-cells have a functional role in man during exercise."}
{"id": "PMID:230456", "title": "The steady state response of brainstem respiratory neuron activity to various levels of PA,CO2 and PA,O2.", "content": "Extracellular recordings were made of 52 respiratory neurons in the brainstem of cats, anesthetized (chloralose-urethane), vagotomized and artificially ventilated. Phrenic nerve activity was recorded and quantified as an index of the output of the respiratory neuronal organization in the brainstem. The unit activity was quantified by using the modal spike frequency as a possible indication of the activating effect of one unit on other respiratory neurons (Smolders and Folgering, 1979). Inspiratory neurons showed the strongest reaction to changes in PA,CO2 and/or PA,O2. Expiratory neurons and frequency modulated neurons responded less to changes in chemical drive. Phase spanning neurons did not show any consistent response. Four out of ten continuously firing neurons without any respiratory rhytmicity increased their firing frequency when PA,CO2 was increased. Apart from the increase in modal spike frequency, the respiratory neuronal organization also reacted with an increase in active units (recruitment) when the chemical drive was increased. The relationship between quantified phrenic nerve activity and spike frequency was independent of the stimulus (hypercapnia or hypoxia). A model was developed in which the increase in modal frequency of a unit arouses other units: when the chemical drive increases, progressively more units tend to be recruited into the respiratory neuronal organization in the brainstem.", "contents": "The steady state response of brainstem respiratory neuron activity to various levels of PA,CO2 and PA,O2. Extracellular recordings were made of 52 respiratory neurons in the brainstem of cats, anesthetized (chloralose-urethane), vagotomized and artificially ventilated. Phrenic nerve activity was recorded and quantified as an index of the output of the respiratory neuronal organization in the brainstem. The unit activity was quantified by using the modal spike frequency as a possible indication of the activating effect of one unit on other respiratory neurons (Smolders and Folgering, 1979). Inspiratory neurons showed the strongest reaction to changes in PA,CO2 and/or PA,O2. Expiratory neurons and frequency modulated neurons responded less to changes in chemical drive. Phase spanning neurons did not show any consistent response. Four out of ten continuously firing neurons without any respiratory rhytmicity increased their firing frequency when PA,CO2 was increased. Apart from the increase in modal spike frequency, the respiratory neuronal organization also reacted with an increase in active units (recruitment) when the chemical drive was increased. The relationship between quantified phrenic nerve activity and spike frequency was independent of the stimulus (hypercapnia or hypoxia). A model was developed in which the increase in modal frequency of a unit arouses other units: when the chemical drive increases, progressively more units tend to be recruited into the respiratory neuronal organization in the brainstem."}
{"id": "PMID:230463", "title": "Purification of the mRNA for chicken very low density lipoproteinII and molecular cloning of its full-length double-stranded cDNA.", "content": "The mRNA coding for the small apo-Very Low Density Lipoprotein (apo-VLDLII) from chicken serum was highly enriched by oligo(dT) chromatography and preparative gel electrophoresis of estrogenised liver RNA. Double-stranded cDNA was synthesised by the subsequent actions of reverse transcriptase and DNA polymerase, and used for a preliminary characterisation of the structural gene. Molecular cloning of dC-tailed ds-cDNA into the Pst I site of plasmid pBR 322 yielded several recombinant clones. Five chimeric DNAs were selected and characterised by restriction enzyme mapping and electron microscopy of R-loops. At least two of them (pVLDLII 3.33 and pVLDLII 4.82) contain an almost full-length ds-transcript of VLDLII mRNA in which no more than 10-20 bases at the 5'- end are missing.", "contents": "Purification of the mRNA for chicken very low density lipoproteinII and molecular cloning of its full-length double-stranded cDNA. The mRNA coding for the small apo-Very Low Density Lipoprotein (apo-VLDLII) from chicken serum was highly enriched by oligo(dT) chromatography and preparative gel electrophoresis of estrogenised liver RNA. Double-stranded cDNA was synthesised by the subsequent actions of reverse transcriptase and DNA polymerase, and used for a preliminary characterisation of the structural gene. Molecular cloning of dC-tailed ds-cDNA into the Pst I site of plasmid pBR 322 yielded several recombinant clones. Five chimeric DNAs were selected and characterised by restriction enzyme mapping and electron microscopy of R-loops. At least two of them (pVLDLII 3.33 and pVLDLII 4.82) contain an almost full-length ds-transcript of VLDLII mRNA in which no more than 10-20 bases at the 5'- end are missing."}
{"id": "PMID:230464", "title": "Synthesis of the human insulin gene. Part II. Further improvements in the modified phosphotriester method and the synthesis of seventeen deoxyribooligonucleotide fragments constituting human insulin chains B and mini-CDNA.", "content": "The purification of protected deoxyribooligonucleotides containing phosphotriester internucleotidic linkages has been improved by developing a deactivated silica gel chromatographic technique. The efficiency of this technique as applied in the modified phosphotriester approach has been demonstrated in the rapid synthesis of seventeen pure fragments constituting the sequence of human insulin B and mini-C DNA. The sequence of each oligomer was confirmed by the two-dimensional mobility shift method of fingerprinting.", "contents": "Synthesis of the human insulin gene. Part II. Further improvements in the modified phosphotriester method and the synthesis of seventeen deoxyribooligonucleotide fragments constituting human insulin chains B and mini-CDNA. The purification of protected deoxyribooligonucleotides containing phosphotriester internucleotidic linkages has been improved by developing a deactivated silica gel chromatographic technique. The efficiency of this technique as applied in the modified phosphotriester approach has been demonstrated in the rapid synthesis of seventeen pure fragments constituting the sequence of human insulin B and mini-C DNA. The sequence of each oligomer was confirmed by the two-dimensional mobility shift method of fingerprinting."}
{"id": "PMID:230465", "title": "Regions of the polyoma genome coding for T antigens.", "content": "The early region of the polyoma genome encodes three T antigens. We have analyzed the organization of the coding regions for the T antigens, using the nucleotide sequence of polyoma DNA and peptides derived from purified, radio-labeled T antigens, separated by two-dimensional electrophoresis and chromatography. We compared the peptides, predicted from the nucleotide sequence of the DNA, with those derived from the purified T antigens. We also compared chemically synthesized peptides, predicted from the DNA sequence, with observed peptides. The results show that the three polyoma T antigens are encoded in overlapping regions of the viral DNA, translated, in part, in two different reading frames.", "contents": "Regions of the polyoma genome coding for T antigens. The early region of the polyoma genome encodes three T antigens. We have analyzed the organization of the coding regions for the T antigens, using the nucleotide sequence of polyoma DNA and peptides derived from purified, radio-labeled T antigens, separated by two-dimensional electrophoresis and chromatography. We compared the peptides, predicted from the nucleotide sequence of the DNA, with those derived from the purified T antigens. We also compared chemically synthesized peptides, predicted from the DNA sequence, with observed peptides. The results show that the three polyoma T antigens are encoded in overlapping regions of the viral DNA, translated, in part, in two different reading frames."}
{"id": "PMID:230466", "title": "Experimental evidence for asymmetrical shielding of nucleosomal DNA by histones.", "content": "Electron spin resonance study of Mn (II) binding to chromatin and derivatives, including core particles, shows that Mn (II) is a good probe for testing the overall electrostatic balance of the nucleoproteic complex as well as DNA accessibility. Experimental results are in good agreement with a recent model proposed (Mirzabekov A. D. and Rich A. (1979) Proc. Natl. Acad. Sci. USA 76, 1118-1121), for the core particle, in which an asymmetrical shielding of DNA by the protein core is assumed. Furthermore, it was found that the histone H1 hinders a number of charges on the linker DNA in a proportion equal to the net positive charge of the histone itself. This result is interpreted as due to a tighter interaction between the linker DNA and the core histones in the presence of histone H1.", "contents": "Experimental evidence for asymmetrical shielding of nucleosomal DNA by histones. Electron spin resonance study of Mn (II) binding to chromatin and derivatives, including core particles, shows that Mn (II) is a good probe for testing the overall electrostatic balance of the nucleoproteic complex as well as DNA accessibility. Experimental results are in good agreement with a recent model proposed (Mirzabekov A. D. and Rich A. (1979) Proc. Natl. Acad. Sci. USA 76, 1118-1121), for the core particle, in which an asymmetrical shielding of DNA by the protein core is assumed. Furthermore, it was found that the histone H1 hinders a number of charges on the linker DNA in a proportion equal to the net positive charge of the histone itself. This result is interpreted as due to a tighter interaction between the linker DNA and the core histones in the presence of histone H1."}
{"id": "PMID:230468", "title": "Intracellular distribution of hepatic and renal gluconeogenic enzymes in embryonic and growing chickens.", "content": "The intracellular distribution of hepatic and renal gluconeogenic enzymes in 20-day-old chicken embryos and 4-week-old chickens (Gallus domesticus: New Hampshire male X Columbian female) has been studied. Pyruvate carboxylase, fructose-1,6-diphosphatase, and glucose-6-phosphatase were found primarily in the mitochondrial, cytosolic, and microsomal fractions, respectively. Phosphenolpyruvate carboxykinase was present not only in the mitochondria but also in the cytosol of the chicken liver and the kidney. The intracellular distribution of the liver enzyme differed from that of the kidney enzyme in chicken embryos as well as in growing chickens.", "contents": "Intracellular distribution of hepatic and renal gluconeogenic enzymes in embryonic and growing chickens. The intracellular distribution of hepatic and renal gluconeogenic enzymes in 20-day-old chicken embryos and 4-week-old chickens (Gallus domesticus: New Hampshire male X Columbian female) has been studied. Pyruvate carboxylase, fructose-1,6-diphosphatase, and glucose-6-phosphatase were found primarily in the mitochondrial, cytosolic, and microsomal fractions, respectively. Phosphenolpyruvate carboxykinase was present not only in the mitochondria but also in the cytosol of the chicken liver and the kidney. The intracellular distribution of the liver enzyme differed from that of the kidney enzyme in chicken embryos as well as in growing chickens."}
{"id": "PMID:230467", "title": "The cholinergic system of the brain and its interactions with other aminergic systems.", "content": "The new achievements in the understanding of acetylcholine (ACh) synthesis, storage, metabolism, the neuronal action, the structure of cholinergic synapses and the nature of cholinergic receptors in the central nervous system are described. Moreover, interactions of cholinergic mechanisms with adrenergic, serotoninergic, GABA-ergic and histaminergic systems in the brain are discussed.", "contents": "The cholinergic system of the brain and its interactions with other aminergic systems. The new achievements in the understanding of acetylcholine (ACh) synthesis, storage, metabolism, the neuronal action, the structure of cholinergic synapses and the nature of cholinergic receptors in the central nervous system are described. Moreover, interactions of cholinergic mechanisms with adrenergic, serotoninergic, GABA-ergic and histaminergic systems in the brain are discussed."}
{"id": "PMID:230475", "title": "Implantation of the isolated human erythrocyte anion channel into plasma membranes of Friend erythroleukemic cells by use of Sendai virus envelopes.", "content": "Sendai virus envelopes and human erythrocyte band 3 membrane polypeptides were isolated in detergent solutions and coreconstituted into detergent-free vesicle structurally resembling viral envelopes. Formation of hybrid viral envelope-band 3 vesicles (VB3) was demonstrated by immunoprecipitation of VB3 containing 4,4'-diisothiocyano-2,2'-ditritostilbenedisulfonic acid-labeled band 3 in the presence of antiviral antiserum. The hybrid VB3 vesicles displayed agglutination, fusion, and hemolytic properties similar to those of reconstituted viral envelopes. Incubation of VB3 with Friend erythroleukemic cells resulted in fusion-mediated insertion of viral antigens and of band 3 into the plasma membranes of the recipient cells. The presence of band 3 incorporated into Friend erythroleukemic cells was revealed structurally by electron microscopy after staining with ferritin-conjugated anti-human erythrocyte membrane antiserum. Incorporation of band 3, the putative erythrocyte antion channel, led to a marked and specific stimulation of anion exchange in Friend erythroleukemic cells. The viral-mediated insertion of an isolated membrane protein into viable Friend erythroleukemic cells provides a method for studying membrane protein turnover and for assaying reconstituted membrane components such as carriers or channels.", "contents": "Implantation of the isolated human erythrocyte anion channel into plasma membranes of Friend erythroleukemic cells by use of Sendai virus envelopes. Sendai virus envelopes and human erythrocyte band 3 membrane polypeptides were isolated in detergent solutions and coreconstituted into detergent-free vesicle structurally resembling viral envelopes. Formation of hybrid viral envelope-band 3 vesicles (VB3) was demonstrated by immunoprecipitation of VB3 containing 4,4'-diisothiocyano-2,2'-ditritostilbenedisulfonic acid-labeled band 3 in the presence of antiviral antiserum. The hybrid VB3 vesicles displayed agglutination, fusion, and hemolytic properties similar to those of reconstituted viral envelopes. Incubation of VB3 with Friend erythroleukemic cells resulted in fusion-mediated insertion of viral antigens and of band 3 into the plasma membranes of the recipient cells. The presence of band 3 incorporated into Friend erythroleukemic cells was revealed structurally by electron microscopy after staining with ferritin-conjugated anti-human erythrocyte membrane antiserum. Incorporation of band 3, the putative erythrocyte antion channel, led to a marked and specific stimulation of anion exchange in Friend erythroleukemic cells. The viral-mediated insertion of an isolated membrane protein into viable Friend erythroleukemic cells provides a method for studying membrane protein turnover and for assaying reconstituted membrane components such as carriers or channels."}
{"id": "PMID:230476", "title": "Binding of inhibitor alters kinetic and physical properties of extracellular cyclic AMP phosphodiesterase from Dictyostelium discoideum.", "content": "The extracellular adenosine 3',5'-cyclic monophosphate phosphodiesterase (3',5'-cyclic-nucleotide 5'-nucleotidohydrolase, EC 3.1.4.17) produced by Dictyostelium discoideum has two kinetic forms. The free enzyme has a Km of approximately 10 microM. The second form is the result of a complex formed with a heat-stable inhibitor and has a Km in the millimolar range. Treating the enzyme-inhibitor complex with dithiothreitol stimulated enzyme activity 20- to 100-fold and changed in Km from millimolar to micromolar. Dithiothreitol inactivated the inhibitor. Reconstituting purified enzyme with excess inhibitor returned the Km to the millimolar range. Under conditions known to inhibit the production of extracellular inhibitor or in mutants that lack it, extracellular phosphodiesterase activity was already high and could not be increased by dithiothreitol. The phosphodiesterase and inhibitor sedimented at 6 S and 3 S, respectively; the enzyme-inhibitor complex sedimented at 6.7 S.", "contents": "Binding of inhibitor alters kinetic and physical properties of extracellular cyclic AMP phosphodiesterase from Dictyostelium discoideum. The extracellular adenosine 3',5'-cyclic monophosphate phosphodiesterase (3',5'-cyclic-nucleotide 5'-nucleotidohydrolase, EC 3.1.4.17) produced by Dictyostelium discoideum has two kinetic forms. The free enzyme has a Km of approximately 10 microM. The second form is the result of a complex formed with a heat-stable inhibitor and has a Km in the millimolar range. Treating the enzyme-inhibitor complex with dithiothreitol stimulated enzyme activity 20- to 100-fold and changed in Km from millimolar to micromolar. Dithiothreitol inactivated the inhibitor. Reconstituting purified enzyme with excess inhibitor returned the Km to the millimolar range. Under conditions known to inhibit the production of extracellular inhibitor or in mutants that lack it, extracellular phosphodiesterase activity was already high and could not be increased by dithiothreitol. The phosphodiesterase and inhibitor sedimented at 6 S and 3 S, respectively; the enzyme-inhibitor complex sedimented at 6.7 S."}
{"id": "PMID:230474", "title": "[Triiodothyronine binding by the liver nuclei and mitochondria].", "content": "The binding of I125-triiodothyronine by male thyroidectomized rat liver nuclei and mitochondria in vivo and in vitro was studied. Labeled triiodothyronine was bound by the liver nuclei and mitochondria proteins. 90% radioactivity was bound by the nuclear nonhistone proteins. The binding of I125-triiodothyronine to the nuclei and mitochondria protein receptors was inhibited by unlabeled triiodothyronine and ICl. It is suggested that aromatic amino acids serve as the binding sites of the protein receptors, and that iodine atoms in the thyroid hormone molecules participated directly in the binding process.", "contents": "[Triiodothyronine binding by the liver nuclei and mitochondria]. The binding of I125-triiodothyronine by male thyroidectomized rat liver nuclei and mitochondria in vivo and in vitro was studied. Labeled triiodothyronine was bound by the liver nuclei and mitochondria proteins. 90% radioactivity was bound by the nuclear nonhistone proteins. The binding of I125-triiodothyronine to the nuclei and mitochondria protein receptors was inhibited by unlabeled triiodothyronine and ICl. It is suggested that aromatic amino acids serve as the binding sites of the protein receptors, and that iodine atoms in the thyroid hormone molecules participated directly in the binding process."}
{"id": "PMID:230477", "title": "Properties and localization of beta-endorphin receptor in rat brain.", "content": "Stereospecific high-affinity binding sites for beta h-[3H]endorphin could be demonstrated in the P2 pellet of rat brain homogenate. Scatchard analysis of the binding data revealed binding sites with Kd values of 0.81 and 6.8 nM and density of 120 and 240 fmol/mg of protein. Distribution of beta h-[3H]endorphin binding in various brain regions parallels that of opiate receptor:striatum greater than thalamus greater than amygdala greater than hypothalamus, septum greater than cortex greater than midbrain, brainstem. Similar to their effect on 3H-labeled agonist binding, Na+ and other monovalent cations, GTP, trypsin, chymotrypsin, phospholipase A2, and N-ethylmaleimide all inhibited the specific binding of beta h-[3H]endorphin. In contrast to their action on alkaloid and enkephalin binding, Ca2+, Mg2+, and Mn2+ also inhibited beta h-[3H]endorphin binding. These data suggest a difference between beta h-endorphin and alkaloid/enkephalin binding sites.", "contents": "Properties and localization of beta-endorphin receptor in rat brain. Stereospecific high-affinity binding sites for beta h-[3H]endorphin could be demonstrated in the P2 pellet of rat brain homogenate. Scatchard analysis of the binding data revealed binding sites with Kd values of 0.81 and 6.8 nM and density of 120 and 240 fmol/mg of protein. Distribution of beta h-[3H]endorphin binding in various brain regions parallels that of opiate receptor:striatum greater than thalamus greater than amygdala greater than hypothalamus, septum greater than cortex greater than midbrain, brainstem. Similar to their effect on 3H-labeled agonist binding, Na+ and other monovalent cations, GTP, trypsin, chymotrypsin, phospholipase A2, and N-ethylmaleimide all inhibited the specific binding of beta h-[3H]endorphin. In contrast to their action on alkaloid and enkephalin binding, Ca2+, Mg2+, and Mn2+ also inhibited beta h-[3H]endorphin binding. These data suggest a difference between beta h-endorphin and alkaloid/enkephalin binding sites."}
{"id": "PMID:230478", "title": "Purification of chicken intestinal receptor for 1,25-dihydroxyvitamin D.", "content": "The 3.3S chicken intestinal receptor for 1,25-dihydroxyvitamin D [1,25-(OH)2D] has been purified approximately 86,000-fold from the cytosolic fraction. The receptor was selectively precipitated with Polymin P from high-speed supernatants derived from 800 g of intestinal mucosa and then sequentially chromatographed on DNA-cellulose. Sephacryl, blue dextran-Sepharose, DNA-cellulose, and heparin-Sepharose. Polyacrylamide gel electrophoresis of 8-10 microgram of the purified receptor in sodium dodecyl sulfate indicated the presence of one major and three minor protein bands of molecular weights 50,000-65,000. Sucrose gradient analysis of the purified material in 0.3 M KCl suggested that a fraction of the receptor remained complexed to the 1,25-(OH)2D and that its sedimentation property of 3.3S remained unchanged. These results represent a major purification of the chick intestinal receptor for 1,25-(OH)2D, an extremely rare and labile protein whose isolation is estimated to require a 200,000-fold purification. Of primary importance is the observation tht affinity ligands such as DNA and blue dextran can effect major purification of this protein, lending credence to the hypothesis that the 1,25-(OH)2D receptor functions within the cell nucleus by altering the expression of specific genes.", "contents": "Purification of chicken intestinal receptor for 1,25-dihydroxyvitamin D. The 3.3S chicken intestinal receptor for 1,25-dihydroxyvitamin D [1,25-(OH)2D] has been purified approximately 86,000-fold from the cytosolic fraction. The receptor was selectively precipitated with Polymin P from high-speed supernatants derived from 800 g of intestinal mucosa and then sequentially chromatographed on DNA-cellulose. Sephacryl, blue dextran-Sepharose, DNA-cellulose, and heparin-Sepharose. Polyacrylamide gel electrophoresis of 8-10 microgram of the purified receptor in sodium dodecyl sulfate indicated the presence of one major and three minor protein bands of molecular weights 50,000-65,000. Sucrose gradient analysis of the purified material in 0.3 M KCl suggested that a fraction of the receptor remained complexed to the 1,25-(OH)2D and that its sedimentation property of 3.3S remained unchanged. These results represent a major purification of the chick intestinal receptor for 1,25-(OH)2D, an extremely rare and labile protein whose isolation is estimated to require a 200,000-fold purification. Of primary importance is the observation tht affinity ligands such as DNA and blue dextran can effect major purification of this protein, lending credence to the hypothesis that the 1,25-(OH)2D receptor functions within the cell nucleus by altering the expression of specific genes."}
{"id": "PMID:230479", "title": "Regulation of synthesis of a major outer membrane protein: cyclic AMP represses Escherichia coli protein III synthesis.", "content": "Cyclic AMP is the effector molecule for both positive and negative control of synthesis of several Escherichia coli proteins. Among the latter is the major outer membrane protein III. The control mechanism occurs at the level of transcription and involves the cyclic AMP receptor protein. The repressing system is saturated at lower concentrations of cyclic AMP than is the positive control system.", "contents": "Regulation of synthesis of a major outer membrane protein: cyclic AMP represses Escherichia coli protein III synthesis. Cyclic AMP is the effector molecule for both positive and negative control of synthesis of several Escherichia coli proteins. Among the latter is the major outer membrane protein III. The control mechanism occurs at the level of transcription and involves the cyclic AMP receptor protein. The repressing system is saturated at lower concentrations of cyclic AMP than is the positive control system."}
{"id": "PMID:230480", "title": "Complementation of the temperature-sensitive defect in H5ts125 adenovirus DNA replication in vitro.", "content": "Soluble extracts of adenovirus-infected HeLa cell nuclei support DNA replication on exogenous adenovirus DNA templates. Conditions of synthesis using both wild-type and temperature-sensitive extracts have been defined. Nuclear extracts prepared from cells permissively infected with the adenovirus mutant H5ts125 expressed the temperature-sensitive phenotype and could be inactivated at 37 degrees C in vitro. These extracts were completely complemented by the addition of wild-type adenovirus DNA binding protein but not by H5ts125 DNA binding protein. Enhancement by binding protein in the mutant extracts represents replication, as demonstrated by the production of full-sized products and orderly chain elongation originating, as in vivo, at both ends of the linear DNA. Replicative synthesis required the 5'-terminal protein bound covalently to template DNA and could be inhibited by denaturation of this 55,000-dalton protein. Various inhibitors of eukaryotic DNA polymerases, such as aphidicolin and 2',3'-dideoxythymidine triphosphate, inhibited replication of exogenous adenovirus templates in this system as they do in previously reported systems that only elongate endogenous replicating intermediates.", "contents": "Complementation of the temperature-sensitive defect in H5ts125 adenovirus DNA replication in vitro. Soluble extracts of adenovirus-infected HeLa cell nuclei support DNA replication on exogenous adenovirus DNA templates. Conditions of synthesis using both wild-type and temperature-sensitive extracts have been defined. Nuclear extracts prepared from cells permissively infected with the adenovirus mutant H5ts125 expressed the temperature-sensitive phenotype and could be inactivated at 37 degrees C in vitro. These extracts were completely complemented by the addition of wild-type adenovirus DNA binding protein but not by H5ts125 DNA binding protein. Enhancement by binding protein in the mutant extracts represents replication, as demonstrated by the production of full-sized products and orderly chain elongation originating, as in vivo, at both ends of the linear DNA. Replicative synthesis required the 5'-terminal protein bound covalently to template DNA and could be inhibited by denaturation of this 55,000-dalton protein. Various inhibitors of eukaryotic DNA polymerases, such as aphidicolin and 2',3'-dideoxythymidine triphosphate, inhibited replication of exogenous adenovirus templates in this system as they do in previously reported systems that only elongate endogenous replicating intermediates."}
{"id": "PMID:230481", "title": "Spliced adenovirus-associated virus RNA.", "content": "We describe the structure of cytoplasmic RNA species transcribed from the DNA of adenovirus-associated virus, a defective parvovirus. The RNA was hybridized with minus strand template DNA and visualized in the electron microscope. Alternatively, the DNA.RNA duplex molecules were digested with nuclease S1 or Escherichia coli exonuclease VII and analyzed by agarose gel electrophoresis. A set of RNA species was observed with 5' terminal at map positions 5, 13, 19, or 39 and a 3' terminus and poly(A) tail at position 96 (one map unit is equivalent to 1% of genome length). Most of these RNAs are spliced and lack sequences approximately between positions 40 and 49. Some RNA preparations also contained unspliced molecules with 5' and 3' terminal at positions similar to those in the spliced RNA.", "contents": "Spliced adenovirus-associated virus RNA. We describe the structure of cytoplasmic RNA species transcribed from the DNA of adenovirus-associated virus, a defective parvovirus. The RNA was hybridized with minus strand template DNA and visualized in the electron microscope. Alternatively, the DNA.RNA duplex molecules were digested with nuclease S1 or Escherichia coli exonuclease VII and analyzed by agarose gel electrophoresis. A set of RNA species was observed with 5' terminal at map positions 5, 13, 19, or 39 and a 3' terminus and poly(A) tail at position 96 (one map unit is equivalent to 1% of genome length). Most of these RNAs are spliced and lack sequences approximately between positions 40 and 49. Some RNA preparations also contained unspliced molecules with 5' and 3' terminal at positions similar to those in the spliced RNA."}
{"id": "PMID:230482", "title": "Solubilization of the low density lipoprotein receptor.", "content": "The low density lipoprotein (LDL) receptor was solubilized from membranes of bovine adrenal cortex and cultured human cells by incubation with the nonionic detergent octyl-beta-D-glucoside. Receptor activity released into the 100,000 x g supernatant was assayed by a solid-phase procedure: an aliquot of the soluble extract was removed, the detergent was diluted below its critical micellar concentration, causing the receptor to precipitate as a lipid-protein aggregate; the precipitate was collected by centrifugation and incubated with (125)I-labeled LDL ((125)I-LDL); and the receptor-bound (125)I-LDL was separated from free (125)I-LDL by filtration. The (125)I-LDL binding site that was precipitated from the soluble extract of bovine adrenocortical membranes appeared to be the same as the functional LDL receptor of cultured bovine adrenocortical cells and human fibroblasts. It exhibited high affinity and specificity (affinity for LDL more than 200-fold greater than for acetylated LDL, methylated LDL, or high density lipoprotein), dependence on calcium, and susceptibility to destruction by Pronase. The amount of (125)I-LDL binding activity in solubilized membranes from cultured cells was proportional to the number of receptors on the surface of the intact cells. Thus, the number of solubilized receptors was 1/20th of normal in mutant fibroblasts from a subject with homozygous familial hypercholesterolemia and was 1/4th of normal in human epithelioid carcinoma A-431 cells when they were grown in the presence of 25-hydroxycholesterol plus cholesterol. While in the soluble form in the presence of octyl-beta-D-glucoside, the LDL receptor can be carried through several steps of purification.", "contents": "Solubilization of the low density lipoprotein receptor. The low density lipoprotein (LDL) receptor was solubilized from membranes of bovine adrenal cortex and cultured human cells by incubation with the nonionic detergent octyl-beta-D-glucoside. Receptor activity released into the 100,000 x g supernatant was assayed by a solid-phase procedure: an aliquot of the soluble extract was removed, the detergent was diluted below its critical micellar concentration, causing the receptor to precipitate as a lipid-protein aggregate; the precipitate was collected by centrifugation and incubated with (125)I-labeled LDL ((125)I-LDL); and the receptor-bound (125)I-LDL was separated from free (125)I-LDL by filtration. The (125)I-LDL binding site that was precipitated from the soluble extract of bovine adrenocortical membranes appeared to be the same as the functional LDL receptor of cultured bovine adrenocortical cells and human fibroblasts. It exhibited high affinity and specificity (affinity for LDL more than 200-fold greater than for acetylated LDL, methylated LDL, or high density lipoprotein), dependence on calcium, and susceptibility to destruction by Pronase. The amount of (125)I-LDL binding activity in solubilized membranes from cultured cells was proportional to the number of receptors on the surface of the intact cells. Thus, the number of solubilized receptors was 1/20th of normal in mutant fibroblasts from a subject with homozygous familial hypercholesterolemia and was 1/4th of normal in human epithelioid carcinoma A-431 cells when they were grown in the presence of 25-hydroxycholesterol plus cholesterol. While in the soluble form in the presence of octyl-beta-D-glucoside, the LDL receptor can be carried through several steps of purification."}
{"id": "PMID:230483", "title": "Synthesis of simian virus 40 t antigen in Escherichia coli.", "content": "Plasmids are constructed by using recombination in vitro according to Roberts, T.M., Kacich, R. & Ptashne, M. (1979) Proc. Natl. Acad. Sci. USA 76, 760-764 in which the t antigen gene of simian virus 40 is fused to a promoter of the Escherichia coli lac operon. In the fusions, transcription commences at the lac promoter, and, in some of the fusions, translation begins at the ATG initiator codon of the t gene. This translation is directed most efficiently by those plasmids in which the lac sequences abut the t gene such that a hybrid ribosome binding is encoded. In this case, the Shine-Dalgarno sequence is of lac origin but the ATG derives from the t gene. translation from this initiator codon is greatly decreased if the lac sequences are separated from the ATG by 17 base pairs and is abolished if the AT of this triplet is deleted. Cells bearing the productive fusions synthesize a 20,000-dalton protein with t antigenic determinants. This protein has an isoelectric point(s) indistinguishable from that of t antigen isolated from simian virus 40-transformed cells. Moreover, a partial sequence of the amino-terminal region of the bacterial product is that predicted for authentic t antigen. We conclude that these bacteria are for authentic t antigen. We conclude that these bacteria are producing a protein, the sequence of which is identical to that of authentic t antigen unfused to other polypeptides.", "contents": "Synthesis of simian virus 40 t antigen in Escherichia coli. Plasmids are constructed by using recombination in vitro according to Roberts, T.M., Kacich, R. & Ptashne, M. (1979) Proc. Natl. Acad. Sci. USA 76, 760-764 in which the t antigen gene of simian virus 40 is fused to a promoter of the Escherichia coli lac operon. In the fusions, transcription commences at the lac promoter, and, in some of the fusions, translation begins at the ATG initiator codon of the t gene. This translation is directed most efficiently by those plasmids in which the lac sequences abut the t gene such that a hybrid ribosome binding is encoded. In this case, the Shine-Dalgarno sequence is of lac origin but the ATG derives from the t gene. translation from this initiator codon is greatly decreased if the lac sequences are separated from the ATG by 17 base pairs and is abolished if the AT of this triplet is deleted. Cells bearing the productive fusions synthesize a 20,000-dalton protein with t antigenic determinants. This protein has an isoelectric point(s) indistinguishable from that of t antigen isolated from simian virus 40-transformed cells. Moreover, a partial sequence of the amino-terminal region of the bacterial product is that predicted for authentic t antigen. We conclude that these bacteria are for authentic t antigen. We conclude that these bacteria are producing a protein, the sequence of which is identical to that of authentic t antigen unfused to other polypeptides."}
{"id": "PMID:230484", "title": "Differentiation as a requirement for simian virus 40 gene expression in F-9 embryonal carcinoma cells.", "content": "Infection of differentiated mouse embryo cells by simian virus 40 (SV40) leads to the production of the early mRNAs and the tumor (T) antigens that they encode. In contrast, undifferentiated F-9 murine teratocarcinoma cells do not support these early stages of the SV40 cycle. This block results from the inability to accumulate stable processed early SV40 mRNAs. It has recently been shown that vitamin A and its derivatives can induce in vitro differentiation of stem cells. Undifferentiated F-9 cells, upon treatment with a low concentration of retinoic acid, exhibited pronounced morphologic changes as well as the appearance of the H-2 surface antigens. After differentiation, the susceptibility of F9 cells to SV40 infection could be demonstrated by the appearance of large T and small T antigens, as shown by immunofluorescence and immunoprecipitation. Furthermore, SI nuclease mapping of early SV40 transcripts confirmed the presence of the two spliced early mRNAs. These results indicate that the undifferentiated F-9 stem cells contain the genetic information needed for generating stable processed early SV40 mRNAs but are blocked in the production of functional species.", "contents": "Differentiation as a requirement for simian virus 40 gene expression in F-9 embryonal carcinoma cells. Infection of differentiated mouse embryo cells by simian virus 40 (SV40) leads to the production of the early mRNAs and the tumor (T) antigens that they encode. In contrast, undifferentiated F-9 murine teratocarcinoma cells do not support these early stages of the SV40 cycle. This block results from the inability to accumulate stable processed early SV40 mRNAs. It has recently been shown that vitamin A and its derivatives can induce in vitro differentiation of stem cells. Undifferentiated F-9 cells, upon treatment with a low concentration of retinoic acid, exhibited pronounced morphologic changes as well as the appearance of the H-2 surface antigens. After differentiation, the susceptibility of F9 cells to SV40 infection could be demonstrated by the appearance of large T and small T antigens, as shown by immunofluorescence and immunoprecipitation. Furthermore, SI nuclease mapping of early SV40 transcripts confirmed the presence of the two spliced early mRNAs. These results indicate that the undifferentiated F-9 stem cells contain the genetic information needed for generating stable processed early SV40 mRNAs but are blocked in the production of functional species."}
{"id": "PMID:230485", "title": "Glycoproteins of Sendai virus are transmembrane proteins.", "content": "Radiolabeled Sendai viral envelope proteins were incorporated into human erythrocyte membranes by the process of fusion of the viral envelope with the erythrocyte membrane. Inside-out (IO) vesicles were prepared from the erythrocyte membranes containing viral proteins, and the presence of viral proteins was assessed by electrophoresis in sodium dodecyl sulfate/polyacrylamide gels. Proteolysis with trypsin, chymotrypsin, or Pronase, which digests only the external surface of the IO vesicles (the cytoplasmic surface of the erythrocyte membrane) revealed that the viral nucleocapsid and the nonglycosylated inner-envelope (M) proteins were present on the external surface. In addition, small segments of the viral envelope glycoproteins (HN and F1) were removed by these proteases, while the major portions of the glycoproteins were protected from digestion, indicating that in the erythrocyte membrane they are transmembrane proteins. Results of experiments carried out on right side-out membranes, unsealed membranes, and membranes containing attached virus that was unable to fuse indicated that the results obtained with IO membranes could not be accounted for by contamination with these membrane species. The identify of the proteolysis products was confirmed by peptide mapping. The selective exposure of the cytoplasmic surface, and hence the internal components of the virus, in IO vesicles makes this membrane system an attractive model for studying the interactions involved in virus maturation at host cell membranes.", "contents": "Glycoproteins of Sendai virus are transmembrane proteins. Radiolabeled Sendai viral envelope proteins were incorporated into human erythrocyte membranes by the process of fusion of the viral envelope with the erythrocyte membrane. Inside-out (IO) vesicles were prepared from the erythrocyte membranes containing viral proteins, and the presence of viral proteins was assessed by electrophoresis in sodium dodecyl sulfate/polyacrylamide gels. Proteolysis with trypsin, chymotrypsin, or Pronase, which digests only the external surface of the IO vesicles (the cytoplasmic surface of the erythrocyte membrane) revealed that the viral nucleocapsid and the nonglycosylated inner-envelope (M) proteins were present on the external surface. In addition, small segments of the viral envelope glycoproteins (HN and F1) were removed by these proteases, while the major portions of the glycoproteins were protected from digestion, indicating that in the erythrocyte membrane they are transmembrane proteins. Results of experiments carried out on right side-out membranes, unsealed membranes, and membranes containing attached virus that was unable to fuse indicated that the results obtained with IO membranes could not be accounted for by contamination with these membrane species. The identify of the proteolysis products was confirmed by peptide mapping. The selective exposure of the cytoplasmic surface, and hence the internal components of the virus, in IO vesicles makes this membrane system an attractive model for studying the interactions involved in virus maturation at host cell membranes."}
{"id": "PMID:230486", "title": "Coupling of opiate receptors to adenylate cyclase: requirement for Na+ and GTP.", "content": "Inhibition of the adenylate cyclase activity in homogenates of mouse neuroblastoma-glioma hybrid cells (NG108-15) by the opioid peptide [D-Ala2,Met5]enkephalin amide (AMEA) requires the presence of Na+ and GTP. In this process, the selectivity for monovalent cations is Na+ greater than or equal Li+ greater than K+ greater than choline+; ITP will replace GTP but ATP, UTP, or CTP will not. The apparent Km for Na+ is 20 mM and for GTP it is 1 microM. Under saturating Na+ and GTP conditions, the apparent Ki for AMEA-directed inhibition is 20 nM for basal and 100 nM for prostaglandin E1-activated adenylate cyclase activity. For both cyclase activities, maximal inhibition is only partial (i.e., approximately 55% of control in each case). In intact viable NG108-15 cells, the decrease in basal and prostaglandin E1-stimulated intracellular cyclic AMP concentrations by AMEA is also dependent upon extracellular Na+. The enkephalin-directed reductions in cyclic AMP concentrations are at least 75%. The specificity of the monovalent cation requirement for enkephalin action on intact cells is the same as for enkephalin regulation of homogenate adenylate cyclase activity. Based on these data, a model is presented in which the transfer of information from opiate receptors to adenylate cyclase requires active separate membrane components, which correspond to the sites of action of Na+ and GTP in this process.", "contents": "Coupling of opiate receptors to adenylate cyclase: requirement for Na+ and GTP. Inhibition of the adenylate cyclase activity in homogenates of mouse neuroblastoma-glioma hybrid cells (NG108-15) by the opioid peptide [D-Ala2,Met5]enkephalin amide (AMEA) requires the presence of Na+ and GTP. In this process, the selectivity for monovalent cations is Na+ greater than or equal Li+ greater than K+ greater than choline+; ITP will replace GTP but ATP, UTP, or CTP will not. The apparent Km for Na+ is 20 mM and for GTP it is 1 microM. Under saturating Na+ and GTP conditions, the apparent Ki for AMEA-directed inhibition is 20 nM for basal and 100 nM for prostaglandin E1-activated adenylate cyclase activity. For both cyclase activities, maximal inhibition is only partial (i.e., approximately 55% of control in each case). In intact viable NG108-15 cells, the decrease in basal and prostaglandin E1-stimulated intracellular cyclic AMP concentrations by AMEA is also dependent upon extracellular Na+. The enkephalin-directed reductions in cyclic AMP concentrations are at least 75%. The specificity of the monovalent cation requirement for enkephalin action on intact cells is the same as for enkephalin regulation of homogenate adenylate cyclase activity. Based on these data, a model is presented in which the transfer of information from opiate receptors to adenylate cyclase requires active separate membrane components, which correspond to the sites of action of Na+ and GTP in this process."}
{"id": "PMID:230487", "title": "Rotational diffusion of cell surface components by time-resolved phosphorescence anisotropy.", "content": "The rotational diffusion of concanavalin A receptors of viable Friend erythroleukemia cells and the band 3 anion transport system of human erythrocytes has been measured via the time-dependent phosphorescence emission intensity and anisotropy of triplet probes excited by a 5-ns laser pulse. High-quality phosphorescence decay curves with a 10-microseconds time resolution were obtained at concentrations of the eosin probe down to 20 nM and in aqueous media at temperatures of 4-38 degrees C. A strong temperature dependence in the rotational behavior was observed for the band 3 anion transport protein, but the lectin receptors of the Friend erythroleukemia cells were found to be immobile on the time scale of 1-4000 microseconds at either 4 degrees C or 37 degrees C. The technique is applicable to other triplet probes and membrane components of living cells under conditions that do not destroy viability.", "contents": "Rotational diffusion of cell surface components by time-resolved phosphorescence anisotropy. The rotational diffusion of concanavalin A receptors of viable Friend erythroleukemia cells and the band 3 anion transport system of human erythrocytes has been measured via the time-dependent phosphorescence emission intensity and anisotropy of triplet probes excited by a 5-ns laser pulse. High-quality phosphorescence decay curves with a 10-microseconds time resolution were obtained at concentrations of the eosin probe down to 20 nM and in aqueous media at temperatures of 4-38 degrees C. A strong temperature dependence in the rotational behavior was observed for the band 3 anion transport protein, but the lectin receptors of the Friend erythroleukemia cells were found to be immobile on the time scale of 1-4000 microseconds at either 4 degrees C or 37 degrees C. The technique is applicable to other triplet probes and membrane components of living cells under conditions that do not destroy viability."}
{"id": "PMID:230488", "title": "Interaction of physalaemin, substance P, and eledoisin with specific membrane receptors on pancreatic acinar cells.", "content": "We have prepared 125I-labeled physalaemin and have examined the kinetics, stoichiometry, and chemical specificity with which the labeled peptide binds to dispersed acini from guinea pig pancreas. Binding of 125I-labeled physalaemin was saturable, temperature-dependent, and reversible and reflected interaction of the labeled peptide with a single class of binding sites on the plasma membrane of pancreatic acinar cells. Each acinar cell possessed approximately 500 binding sites, and binding of the tracer to these sites could be inhibited by physalaemin [concentration for half-maximal effect (Kd), 2 nM], substance P (Kd, 5 nM), or eledoisin (Kd, 300 nM) but not by cholecystokinin, caerulein, bombesin, litorin, gastrin, secretin, vasoactive intestinal peptide, glucagon, somatostatin, neurotensin, bovine pancreatic polypeptide, leucine-enkephalin, methionine-enkephalin, atropine, or carbamylcholine. With physalaemin, substance P, and eledoisin, there was a close correlation between the relative potency for inhibition of binding of labeled physalaemin and that for stimulation of amylase secretion. For a given peptide, however, a 3-fold higher concentration was required for half-maximal inhibition of binding than for half-maximal stimulation of amylase secretion, calcium outflux, or cyclic GMP accumulation. These results indicate that dispersed acini from guinea pig pancreas possess a single class of receptors that interact with physalaemin, substance P, and eledoisin and that occupation of 45% of these receptors will cause a maximal biological response.", "contents": "Interaction of physalaemin, substance P, and eledoisin with specific membrane receptors on pancreatic acinar cells. We have prepared 125I-labeled physalaemin and have examined the kinetics, stoichiometry, and chemical specificity with which the labeled peptide binds to dispersed acini from guinea pig pancreas. Binding of 125I-labeled physalaemin was saturable, temperature-dependent, and reversible and reflected interaction of the labeled peptide with a single class of binding sites on the plasma membrane of pancreatic acinar cells. Each acinar cell possessed approximately 500 binding sites, and binding of the tracer to these sites could be inhibited by physalaemin [concentration for half-maximal effect (Kd), 2 nM], substance P (Kd, 5 nM), or eledoisin (Kd, 300 nM) but not by cholecystokinin, caerulein, bombesin, litorin, gastrin, secretin, vasoactive intestinal peptide, glucagon, somatostatin, neurotensin, bovine pancreatic polypeptide, leucine-enkephalin, methionine-enkephalin, atropine, or carbamylcholine. With physalaemin, substance P, and eledoisin, there was a close correlation between the relative potency for inhibition of binding of labeled physalaemin and that for stimulation of amylase secretion. For a given peptide, however, a 3-fold higher concentration was required for half-maximal inhibition of binding than for half-maximal stimulation of amylase secretion, calcium outflux, or cyclic GMP accumulation. These results indicate that dispersed acini from guinea pig pancreas possess a single class of receptors that interact with physalaemin, substance P, and eledoisin and that occupation of 45% of these receptors will cause a maximal biological response."}
{"id": "PMID:230489", "title": "Hormone receptor topology and dynamics: morphological analysis using ferritin-labeled epidermal growth factor.", "content": "Previous studies using a biologically active 1:1 conjugate of EGF and ferritin (F-EGF) have traced the binding and internalization of the hormone molecules. In the present report, we develop ultrastructural criteria for identification of the F-EGF.receptor complex, and, thereby, enable utilization of the F-EGF as an indirect marker to localize the receptor for this peptide hormone. The ferritin cores of bound F-EGF are situated 4-6 nm from the extracellular surface of the membrane. When cells were incubated for up to 30 min at 37 degrees C, this characteristic spatial relationship was observed in all uptake stages (surface clustering, endocytosis, and incorporation into multivesicular bodies), indicating that the hormone.receptor complex remains intact through these steps. However, when incubation was continued for periods sufficient to allow hormone degradation (30-60 min), pools of free ferritin were observed in lysosomes. In the presence of various amine inhibitors of hormone degradation, internalization and multivesicular body incorporation proceeded, but hormone.receptor degradation was blocked as evidenced by preservation of the ferritin-membrane relationship; i.e., no pools of free ferritin were seen after 60 min. These data provide morphological support for the hypothesis that down-regulation of surface receptors involves internalization of intact hormone.receptor complexes. In addition, we have developed a method for viewing the surface of intact cells en face, allowing closer scrutiny of the clustering of F-EGF.receptor complexes in the plane of the membrane prior to internalization. The particles in the F-EGF clusters observed by this method are spaced at 12 nm center-to-center, serving to set upper limits on the packing dimensions of the EGF.receptor complex.", "contents": "Hormone receptor topology and dynamics: morphological analysis using ferritin-labeled epidermal growth factor. Previous studies using a biologically active 1:1 conjugate of EGF and ferritin (F-EGF) have traced the binding and internalization of the hormone molecules. In the present report, we develop ultrastructural criteria for identification of the F-EGF.receptor complex, and, thereby, enable utilization of the F-EGF as an indirect marker to localize the receptor for this peptide hormone. The ferritin cores of bound F-EGF are situated 4-6 nm from the extracellular surface of the membrane. When cells were incubated for up to 30 min at 37 degrees C, this characteristic spatial relationship was observed in all uptake stages (surface clustering, endocytosis, and incorporation into multivesicular bodies), indicating that the hormone.receptor complex remains intact through these steps. However, when incubation was continued for periods sufficient to allow hormone degradation (30-60 min), pools of free ferritin were observed in lysosomes. In the presence of various amine inhibitors of hormone degradation, internalization and multivesicular body incorporation proceeded, but hormone.receptor degradation was blocked as evidenced by preservation of the ferritin-membrane relationship; i.e., no pools of free ferritin were seen after 60 min. These data provide morphological support for the hypothesis that down-regulation of surface receptors involves internalization of intact hormone.receptor complexes. In addition, we have developed a method for viewing the surface of intact cells en face, allowing closer scrutiny of the clustering of F-EGF.receptor complexes in the plane of the membrane prior to internalization. The particles in the F-EGF clusters observed by this method are spaced at 12 nm center-to-center, serving to set upper limits on the packing dimensions of the EGF.receptor complex."}
{"id": "PMID:230490", "title": "Passage of phenotypes of chemically transformed cells via transfection of DNA and chromatin.", "content": "DNA was prepared from 15 different mouse and rat cell lines transformed by chemical carcinogens in vitro and in vivo. These DNAs were applied to NIH3T3 mouse fibroblast cultures by using the calcium phosphate transfection technique. DNAs of five donor lines were able to induce foci on the recipient monolayers. Ten other donor DNAs yielded few or no foci. DNAs from control, nontransformed parental cell lines induced few or no foci. Chromosomes were transfected from one donor whose naked DNA was unable to induce foci, and morphologic transformation of recipients was observed. These experiments prove that in five of these cell lines the chemically induced phenotype is encoded in DNA, and the sequences specifying the transformed phenotype behave as a dominant allele in the NIH3T3 recipient cells. The sequences encoding the transformation are likely found on a single fragment of DNA.", "contents": "Passage of phenotypes of chemically transformed cells via transfection of DNA and chromatin. DNA was prepared from 15 different mouse and rat cell lines transformed by chemical carcinogens in vitro and in vivo. These DNAs were applied to NIH3T3 mouse fibroblast cultures by using the calcium phosphate transfection technique. DNAs of five donor lines were able to induce foci on the recipient monolayers. Ten other donor DNAs yielded few or no foci. DNAs from control, nontransformed parental cell lines induced few or no foci. Chromosomes were transfected from one donor whose naked DNA was unable to induce foci, and morphologic transformation of recipients was observed. These experiments prove that in five of these cell lines the chemically induced phenotype is encoded in DNA, and the sequences specifying the transformed phenotype behave as a dominant allele in the NIH3T3 recipient cells. The sequences encoding the transformation are likely found on a single fragment of DNA."}
{"id": "PMID:230491", "title": "Antibodies to Epstein-Barr virus-determined antigens in normal subjects and in patients with seropositive rheumatoid arthritis.", "content": "Prior studies have shown that patients with seropositive rheumatoid arthritis (RA) have an increased frequency of precipitating antibody against a nuclear antigen, the RA nuclear antigen, detected in human B lymphoblastoid cell lines infected by Epstein-Barr virus. The present investigations demonstrate that patients with seropositive RA also have specifically elevated titers of antibodies to another, better-characterized Epstein-Barr virus-associated B cell antigen, the Epstein-Barr nuclear antigen, which is detected by anti-complement immunofluorescence. Titers of these two antibodies were not affected by absorption of rheumatoid factor from serum. Furthermore, patients with RA did not have elevated titers of antibodies against the Epstein-Barr virus capsid antigen or to three other species of human herpesviruses: herpes simplex type 1, varicella-zoster virus, and cytomegalovirus. In both normal individuals and RA patients there was a significant association between the presence of antibodies to RA nuclear antigen and the titers of antibody to Epstein-Barr nuclear antigen. Thus, normal subjects with antibody to RA nuclear antigen had titers of antibody to Epstein-Barr nuclear antigen equivalent to those of patients with RA and significantly higher than normal subjects lacking antibody to RA nuclear antigen. One interpretation of these results is that patients with seropositive RA derive from a larger population with enhanced immune responsiveness to B lymphocyte nuclear antigens determined by the Epstein-Barr virus.", "contents": "Antibodies to Epstein-Barr virus-determined antigens in normal subjects and in patients with seropositive rheumatoid arthritis. Prior studies have shown that patients with seropositive rheumatoid arthritis (RA) have an increased frequency of precipitating antibody against a nuclear antigen, the RA nuclear antigen, detected in human B lymphoblastoid cell lines infected by Epstein-Barr virus. The present investigations demonstrate that patients with seropositive RA also have specifically elevated titers of antibodies to another, better-characterized Epstein-Barr virus-associated B cell antigen, the Epstein-Barr nuclear antigen, which is detected by anti-complement immunofluorescence. Titers of these two antibodies were not affected by absorption of rheumatoid factor from serum. Furthermore, patients with RA did not have elevated titers of antibodies against the Epstein-Barr virus capsid antigen or to three other species of human herpesviruses: herpes simplex type 1, varicella-zoster virus, and cytomegalovirus. In both normal individuals and RA patients there was a significant association between the presence of antibodies to RA nuclear antigen and the titers of antibody to Epstein-Barr nuclear antigen. Thus, normal subjects with antibody to RA nuclear antigen had titers of antibody to Epstein-Barr nuclear antigen equivalent to those of patients with RA and significantly higher than normal subjects lacking antibody to RA nuclear antigen. One interpretation of these results is that patients with seropositive RA derive from a larger population with enhanced immune responsiveness to B lymphocyte nuclear antigens determined by the Epstein-Barr virus."}
{"id": "PMID:230492", "title": "Triene prostaglandins: prostaglandin D3 and icosapentaenoic acid as potential antithrombotic substances.", "content": "Addition of the 3-series fatty acid precursor (icosapentaenoic acid, IPA), its endoperoxide [prostaglandin (PG)H(3)], or thromboxane A(3) to human platelet-rich plasma (PRP) does not result in aggregation of the platelets. In fact, preincubation of human PRP with exogenous PGH(3) actually inhibited aggregation by increasing platelet cyclic AMP concentrations. PGH(3) undergoes rapid spontaneous degradation to PGD(3) in human PRP. The PGD(3) so formed is adequate to account for the increase of platelet cAMP and inhibition of aggregation. Furthermore, addition of PGD-specific antisera to human PRP blocked the platelet inhibitory activity of exogenous PGH(3). PGD(3) has considerable potential as a circulating antithrombotic agent. Pretreatment of human PRP with the adenylate cyclase inhibitor 2',5'-dideoxyadenosine blocked the increase of platelet cyclic AMP and the inhibition of aggregation normally produced by PGI(2), PGE(1), PGD(2), PGH(3), and PGD(3). Furthermore, the dideoxyadenosine unmasked a direct but moderate reversible aggregatory effect in response to the subsequent addition of PGH(3). Similarly, the dideoxyadenosine markedly enhanced the aggregation produced by exogenous PGH(2). IPA is readily incorporated into tissue lipids but proved to be a poor substrate for kidney, blood vessel, or heart cyclooxygenase. IPA was previously shown to be a poor substrate for platelet cyclooxygenase. IPA is readily deacylated from the renal phospholipid pool in response to bradykinin, a substance that also stimulates the release of arachidonic acid. A diet that relies primarily on cold-water fish, as in the case of the Greenland Eskimos, lowers endogenous arachidonic acid and markedly increases the IPA content of tissue lipids. Thus, because IPA has the potential to act as an antagonist with arachidonic acid for platelet cyclooxygenase and lipoxygenase, the simultaneous release of IPA could suppress any residual arachidonic acid conversion to its aggregatory metabolites.", "contents": "Triene prostaglandins: prostaglandin D3 and icosapentaenoic acid as potential antithrombotic substances. Addition of the 3-series fatty acid precursor (icosapentaenoic acid, IPA), its endoperoxide [prostaglandin (PG)H(3)], or thromboxane A(3) to human platelet-rich plasma (PRP) does not result in aggregation of the platelets. In fact, preincubation of human PRP with exogenous PGH(3) actually inhibited aggregation by increasing platelet cyclic AMP concentrations. PGH(3) undergoes rapid spontaneous degradation to PGD(3) in human PRP. The PGD(3) so formed is adequate to account for the increase of platelet cAMP and inhibition of aggregation. Furthermore, addition of PGD-specific antisera to human PRP blocked the platelet inhibitory activity of exogenous PGH(3). PGD(3) has considerable potential as a circulating antithrombotic agent. Pretreatment of human PRP with the adenylate cyclase inhibitor 2',5'-dideoxyadenosine blocked the increase of platelet cyclic AMP and the inhibition of aggregation normally produced by PGI(2), PGE(1), PGD(2), PGH(3), and PGD(3). Furthermore, the dideoxyadenosine unmasked a direct but moderate reversible aggregatory effect in response to the subsequent addition of PGH(3). Similarly, the dideoxyadenosine markedly enhanced the aggregation produced by exogenous PGH(2). IPA is readily incorporated into tissue lipids but proved to be a poor substrate for kidney, blood vessel, or heart cyclooxygenase. IPA was previously shown to be a poor substrate for platelet cyclooxygenase. IPA is readily deacylated from the renal phospholipid pool in response to bradykinin, a substance that also stimulates the release of arachidonic acid. A diet that relies primarily on cold-water fish, as in the case of the Greenland Eskimos, lowers endogenous arachidonic acid and markedly increases the IPA content of tissue lipids. Thus, because IPA has the potential to act as an antagonist with arachidonic acid for platelet cyclooxygenase and lipoxygenase, the simultaneous release of IPA could suppress any residual arachidonic acid conversion to its aggregatory metabolites."}
{"id": "PMID:230493", "title": "Changes in plasma lipoprotein distribution and formation of two unusual particles after heparin-induced lipolysis in hypertriglyceridemic subjects.", "content": "Lipoprotein morphology and distribution were studied in three moderately to severely hypertriglyceridemic patients after heparin-induced lipolysis. Lipoproteins with a flotation rate of Sf degrees 12-20 in rho 1.063-g/ml NaCl solution increased substantially in mass 2.5-10 min after heparin administration. This fraction contained 40- to 120-nm flattened particles and increased concentrations of phospholipid and free cholesterol. At 2.5 and 10 min after heparin, the high density lipoproteins (HDL) of rho, 1.126-1.21 g/ml contained small (5.8-nm diameter) spherical particles. Both types of particles disappeared 30-60 min after heparin. Results indicated that with lipolysis HDL3 may be transformed into HDL2a by incorporation of chylomicron and very low density lipoprotein constituents. It is suggested that the 40- to 120-nm particles represent surface fragments of chylomicrons and very low density lipoproteins generated during lipolysis, whereas the 5.8-nm particles are produced either by fragmentation of the large surface constituents or by loss of lipid from existing HDL3.", "contents": "Changes in plasma lipoprotein distribution and formation of two unusual particles after heparin-induced lipolysis in hypertriglyceridemic subjects. Lipoprotein morphology and distribution were studied in three moderately to severely hypertriglyceridemic patients after heparin-induced lipolysis. Lipoproteins with a flotation rate of Sf degrees 12-20 in rho 1.063-g/ml NaCl solution increased substantially in mass 2.5-10 min after heparin administration. This fraction contained 40- to 120-nm flattened particles and increased concentrations of phospholipid and free cholesterol. At 2.5 and 10 min after heparin, the high density lipoproteins (HDL) of rho, 1.126-1.21 g/ml contained small (5.8-nm diameter) spherical particles. Both types of particles disappeared 30-60 min after heparin. Results indicated that with lipolysis HDL3 may be transformed into HDL2a by incorporation of chylomicron and very low density lipoprotein constituents. It is suggested that the 40- to 120-nm particles represent surface fragments of chylomicrons and very low density lipoproteins generated during lipolysis, whereas the 5.8-nm particles are produced either by fragmentation of the large surface constituents or by loss of lipid from existing HDL3."}
{"id": "PMID:230494", "title": "Reactivation of herpes simplex virus type 2 from a quiescent state by human cytomegalovirus.", "content": "The ability of human cytomegalovirus to stimulate replication of herpes simplex virus type 2 (HSV-2) was examined. The system used involved HSV-2-infected human embryonic lung cells under conditions (39.5-40 degrees C) in which HSV-2 remains undetectable. Reactivation of HSV-2 was maximal and persisted for the longest duration when cultures were superinfected with 0.02 plaque-forming unit of human cytomegalovirus per cell. Infectious HSV-2 appeared 2 days after superinfection with human cytomegalovirus and ranged from 10(2) to 10(6) plaque-forming units per culture. Virus reactivated from these cultures was neutralized by rabbit immune serum produced against HSV-2. The specificity of this interaction was demonstrated by various criteria: production of HSV-2 was not observed in cultures treated with mock infecting fluid, and inactivation of human cytomegalovirus by heat, ultraviolet irradiation, or immune serum prior to superinfection eliminated its ability to induce HSV-2 replication. These results sugges that interaction between these two human herpesviruses may be of importance in herpesvirus latency in vivo.", "contents": "Reactivation of herpes simplex virus type 2 from a quiescent state by human cytomegalovirus. The ability of human cytomegalovirus to stimulate replication of herpes simplex virus type 2 (HSV-2) was examined. The system used involved HSV-2-infected human embryonic lung cells under conditions (39.5-40 degrees C) in which HSV-2 remains undetectable. Reactivation of HSV-2 was maximal and persisted for the longest duration when cultures were superinfected with 0.02 plaque-forming unit of human cytomegalovirus per cell. Infectious HSV-2 appeared 2 days after superinfection with human cytomegalovirus and ranged from 10(2) to 10(6) plaque-forming units per culture. Virus reactivated from these cultures was neutralized by rabbit immune serum produced against HSV-2. The specificity of this interaction was demonstrated by various criteria: production of HSV-2 was not observed in cultures treated with mock infecting fluid, and inactivation of human cytomegalovirus by heat, ultraviolet irradiation, or immune serum prior to superinfection eliminated its ability to induce HSV-2 replication. These results sugges that interaction between these two human herpesviruses may be of importance in herpesvirus latency in vivo."}
{"id": "PMID:230495", "title": "Apolipoprotein is responsible for neutralization of xenotropic type C virus by mouse serum.", "content": "We have shown that the circulating lipoproteins of the mouse contain a potent inhibitor of infectivity of the xenotropic type C virus. This virus neutralization does not involve immunoglobulins or complement. After fractionation of the lipoproteins on the basis of particle size, flotation properties, and electrostatic charge, virus neutralizing activity is found primarily in the triglyceride-rich lipoproteins (predominantly the chylomicrons) and in the HDL(2) subfraction of the high density lipoproteins. In fasted animals, activity resides chiefly in the high density lipoproteins. Neutralization titers increase strikingly during alimentary lipemia in both the lipoproteins of the rho < 1.006 g/cm(3) fraction and the high density lipoproteins. Increased activity persists in the high density lipoproteins after the lipemia recedes. Virus neutralizing activity is completely eliminated in all fractions by antiserum against high density lipoproteins and, in the triglyceride-rich fractions, by antiserum to murine apolipoprotein B. Complete removal of lipids markedly reduces the neutralizing activity of both classes of lipoproteins. Apolipoproteins delipidated with tetramethylurea retain some activity, which is enhanced by binding to a phospholipid-stabilized triglyceride emulsion and which is abolished by proteolytic digestion. We have demonstrated in vitro transfer of activity between high density and very low density lipoproteins of the mouse. These data indicate that xenotropic virus neutralization by normal mouse serum depends upon a protein that transfers among lipoprotein particles in a fashion analogous to the C apolipoproteins of other mammalian species.", "contents": "Apolipoprotein is responsible for neutralization of xenotropic type C virus by mouse serum. We have shown that the circulating lipoproteins of the mouse contain a potent inhibitor of infectivity of the xenotropic type C virus. This virus neutralization does not involve immunoglobulins or complement. After fractionation of the lipoproteins on the basis of particle size, flotation properties, and electrostatic charge, virus neutralizing activity is found primarily in the triglyceride-rich lipoproteins (predominantly the chylomicrons) and in the HDL(2) subfraction of the high density lipoproteins. In fasted animals, activity resides chiefly in the high density lipoproteins. Neutralization titers increase strikingly during alimentary lipemia in both the lipoproteins of the rho < 1.006 g/cm(3) fraction and the high density lipoproteins. Increased activity persists in the high density lipoproteins after the lipemia recedes. Virus neutralizing activity is completely eliminated in all fractions by antiserum against high density lipoproteins and, in the triglyceride-rich fractions, by antiserum to murine apolipoprotein B. Complete removal of lipids markedly reduces the neutralizing activity of both classes of lipoproteins. Apolipoproteins delipidated with tetramethylurea retain some activity, which is enhanced by binding to a phospholipid-stabilized triglyceride emulsion and which is abolished by proteolytic digestion. We have demonstrated in vitro transfer of activity between high density and very low density lipoproteins of the mouse. These data indicate that xenotropic virus neutralization by normal mouse serum depends upon a protein that transfers among lipoprotein particles in a fashion analogous to the C apolipoproteins of other mammalian species."}
{"id": "PMID:230496", "title": "Chronic treatment with lithium or desipramine alters discharge frequency and norepinephrine responsiveness of cerebellar Purkinje cells.", "content": "Cerebellar Purkinje cells were studied by electrophysiological techniques in rats treated chronically with either desipramine (DMI) or lithium chloride given intragastrically. A striking decrement occurred in discharge frequencies of simple spikes and climbing fiber bursts in both groups of animals, similar to the depression produced by iontophoresis of these agents. Chronic treatment with DMI markedly decreased responsiveness to iontophoretically applied norepinephrine (NE), whereas long-term LiCl therapy slightly enhanced response to NE; responses to gamma-aminobutyric acid were unchanged by these treatments. The inhibitory responses to locus ceruleus stimulation were unaffected by chronic LiCl treatment. The effects of these chronic treatments on responsiveness to NE are opposite to the effects these same drugs produce when administered by acute iontophoresis to single cells: DMI then potentiates and LiCl antagonizes noradrenergic responses. These results provide electrophysiological evidence for reciprocal adaptive changes in NE sensitivity, supporting results of biochemical studies.", "contents": "Chronic treatment with lithium or desipramine alters discharge frequency and norepinephrine responsiveness of cerebellar Purkinje cells. Cerebellar Purkinje cells were studied by electrophysiological techniques in rats treated chronically with either desipramine (DMI) or lithium chloride given intragastrically. A striking decrement occurred in discharge frequencies of simple spikes and climbing fiber bursts in both groups of animals, similar to the depression produced by iontophoresis of these agents. Chronic treatment with DMI markedly decreased responsiveness to iontophoretically applied norepinephrine (NE), whereas long-term LiCl therapy slightly enhanced response to NE; responses to gamma-aminobutyric acid were unchanged by these treatments. The inhibitory responses to locus ceruleus stimulation were unaffected by chronic LiCl treatment. The effects of these chronic treatments on responsiveness to NE are opposite to the effects these same drugs produce when administered by acute iontophoresis to single cells: DMI then potentiates and LiCl antagonizes noradrenergic responses. These results provide electrophysiological evidence for reciprocal adaptive changes in NE sensitivity, supporting results of biochemical studies."}
{"id": "PMID:230497", "title": "Protein and phospholipid methylation during chemotaxis in Dictyostelium discoideum and its relationship to calcium movements.", "content": "Suspensions of cyclic AMP sensitive cells of Dictyostelium discoideum responded to a cyclic AMP pulse with increased methylation of a protein of molecular weight about 120,000 and increased phospholipid demethylation. Protein methylation reached its peak 15-30 sec after cyclic AMP addition. Phospholipid demethylation reached its maximum within 2 min and basal levels were recovered in 3 min. S-Adenosyl-L-methionine is probably the methyl donor. In vitro addition of 0.25 mM and 25 microM S-adenosyl-L-methionine to sonicated D. discoideum cells inhibited ATP-dependent 45Ca2+ uptake by 70% and 25%, respectively. Based on these lines of evidence we propose that protein and phospholipid methylation are involved in D. discoideum chemotaxis probably by regulation of intracellular Ca2+ movements.", "contents": "Protein and phospholipid methylation during chemotaxis in Dictyostelium discoideum and its relationship to calcium movements. Suspensions of cyclic AMP sensitive cells of Dictyostelium discoideum responded to a cyclic AMP pulse with increased methylation of a protein of molecular weight about 120,000 and increased phospholipid demethylation. Protein methylation reached its peak 15-30 sec after cyclic AMP addition. Phospholipid demethylation reached its maximum within 2 min and basal levels were recovered in 3 min. S-Adenosyl-L-methionine is probably the methyl donor. In vitro addition of 0.25 mM and 25 microM S-adenosyl-L-methionine to sonicated D. discoideum cells inhibited ATP-dependent 45Ca2+ uptake by 70% and 25%, respectively. Based on these lines of evidence we propose that protein and phospholipid methylation are involved in D. discoideum chemotaxis probably by regulation of intracellular Ca2+ movements."}
{"id": "PMID:230498", "title": "A topoisomerase from Escherichia coli related to DNA gyrase.", "content": "We have identified a topoisomerase activity from Escherichia coli related to DNA gyrase (topoisomerase II): we designate it topoisomerase II'. It was constructed of two subunits, which were purified separately. One is the product of the gyrA (formerly nalA) gene and is identical to subunit A of DNA gyrase. The other is a 50,000-dalton protein, which we have purified to homogeneity and call v. v may be a processed form of the much larger gyrase subunit B or may be derived from a transcript of part of the subunit B structural gene, because preliminary peptide maps of the two subunits are similar. Topoisomerase II' relaxes negatively supercoiled DNA and, uniquely among E. coli topoisomerases, relaxes positive supercoils efficiently. It is the only topoisomerase that can introduce positive supercoils; these are stoichiometric with enzyme molecules. Topoisomerase II' resembles gyrase in its sensitivity to oxolinic acid, the wrapping of DNA in an apparent positive supercoil around the enzyme, and the introduction in an aborted reaction of site-specific double-strand breaks in the DNA with concomitant covalent attachment of protein to both newly created 5' ends. Unlike DNA gyrase, topoisomerase II' has no negative supercoiling activity. Functional chimeric topoisomerases were constructed with the alpha subunit of the Micrococcus luteus gyrase and v or gyrase subunit B from E. coli. We discuss the implications of the dual of the gyrA gene product.", "contents": "A topoisomerase from Escherichia coli related to DNA gyrase. We have identified a topoisomerase activity from Escherichia coli related to DNA gyrase (topoisomerase II): we designate it topoisomerase II'. It was constructed of two subunits, which were purified separately. One is the product of the gyrA (formerly nalA) gene and is identical to subunit A of DNA gyrase. The other is a 50,000-dalton protein, which we have purified to homogeneity and call v. v may be a processed form of the much larger gyrase subunit B or may be derived from a transcript of part of the subunit B structural gene, because preliminary peptide maps of the two subunits are similar. Topoisomerase II' relaxes negatively supercoiled DNA and, uniquely among E. coli topoisomerases, relaxes positive supercoils efficiently. It is the only topoisomerase that can introduce positive supercoils; these are stoichiometric with enzyme molecules. Topoisomerase II' resembles gyrase in its sensitivity to oxolinic acid, the wrapping of DNA in an apparent positive supercoil around the enzyme, and the introduction in an aborted reaction of site-specific double-strand breaks in the DNA with concomitant covalent attachment of protein to both newly created 5' ends. Unlike DNA gyrase, topoisomerase II' has no negative supercoiling activity. Functional chimeric topoisomerases were constructed with the alpha subunit of the Micrococcus luteus gyrase and v or gyrase subunit B from E. coli. We discuss the implications of the dual of the gyrA gene product."}
{"id": "PMID:230499", "title": "Mutational analysis of the simian virus 40 replicon: pseudorevertants of mutants with a defective replication origin.", "content": "The circular genome of simian virus 40 is a model mammalian replicon, containing a unique origin of replication (ori) and coding for a protein (SV40 T antigen) known to be involved in initiation of viral DNA replication and to bind in vitro to the origin region. Mutations within the ori sequence lead to defective viral DNA replication and the formation of small viral plaques after infection of a cell monolayer. Second-site revertants (pseudorevertants) of ori mutants were isolated by random local mutagenesis of mutant DNA followed by transfection of cultured cells and the selection of large plaques. In each case, reversion of the plaque phenotype was associated with an increased rate of viral DNA replication. The second-site mutations that suppressed the replication defects were localized by in vitro recombination or marker rescue experiments to the gene for T antigen. Their map positions differ from those of previously described T antigen mutants, possibly reflecting a specific ori-binding domain of T antigen. From these results we infer that T antigen interacts with the ori signal during virus development as it does in vitro and that this interaction regulates the rate of viral DNA replication.", "contents": "Mutational analysis of the simian virus 40 replicon: pseudorevertants of mutants with a defective replication origin. The circular genome of simian virus 40 is a model mammalian replicon, containing a unique origin of replication (ori) and coding for a protein (SV40 T antigen) known to be involved in initiation of viral DNA replication and to bind in vitro to the origin region. Mutations within the ori sequence lead to defective viral DNA replication and the formation of small viral plaques after infection of a cell monolayer. Second-site revertants (pseudorevertants) of ori mutants were isolated by random local mutagenesis of mutant DNA followed by transfection of cultured cells and the selection of large plaques. In each case, reversion of the plaque phenotype was associated with an increased rate of viral DNA replication. The second-site mutations that suppressed the replication defects were localized by in vitro recombination or marker rescue experiments to the gene for T antigen. Their map positions differ from those of previously described T antigen mutants, possibly reflecting a specific ori-binding domain of T antigen. From these results we infer that T antigen interacts with the ori signal during virus development as it does in vitro and that this interaction regulates the rate of viral DNA replication."}
{"id": "PMID:230500", "title": "Electron-nuclear double resonance of the hydrogen peroxide compound of cytochrome c peroxidase: identification of the free radical site with a methionyl cluster.", "content": "The results of electron-nuclear double resonance and electron paramagnetic resonance (EPR) studies on the hydrogen peroxide compound of yeast cytochrome c peroxidase are inconsistent with previous proposals for the source of the EPR signal in this compound, in particular with its identification with an aromatic amino acid radical such as would arise by oxidation of a tryptophanyl side chain. The present observations lead us to propose that the EPR signal is associated with a cluster containing at least one methionine and in which proximate side chains share the charge created by loss of one electron.", "contents": "Electron-nuclear double resonance of the hydrogen peroxide compound of cytochrome c peroxidase: identification of the free radical site with a methionyl cluster. The results of electron-nuclear double resonance and electron paramagnetic resonance (EPR) studies on the hydrogen peroxide compound of yeast cytochrome c peroxidase are inconsistent with previous proposals for the source of the EPR signal in this compound, in particular with its identification with an aromatic amino acid radical such as would arise by oxidation of a tryptophanyl side chain. The present observations lead us to propose that the EPR signal is associated with a cluster containing at least one methionine and in which proximate side chains share the charge created by loss of one electron."}
{"id": "PMID:230501", "title": "Internal genome deletions in two distinct classes of defective interfering particles of vesicular stomatitis virus.", "content": "We have characterized the genome sequences represented in two defective interfering particles derived from the heat-resistant strain of vesicular stomatitis virus by means of end-labeling and hybridization techniques. Both defective particle RNAs, which differ slightly in size, contain 5'-end sequences identical to each other and to that of the standard infectious virus genome, for at least the first approximately 55 bases. In contrast, the 3'-end sequences of these two RNAs are different. The 3'-end sequence of the smaller RNA is identical to that of the standard genome for at least the first 48 bases. The 3'-end sequence of the larger RNA is an inverted complement of its 5' end for approximately 65 bases. The bulk of the sequences in both RNAs is derived from the 3' half of the standard genome. We also show that the two defective particles differ in vitro transcription and in vivo replication properties. These results provide direct evidence for the presence of internal genome deletions in defective interfering particles of negative-stranded RNA animal viruses and demonstrate the existence of at least two distinct classes of these particles.", "contents": "Internal genome deletions in two distinct classes of defective interfering particles of vesicular stomatitis virus. We have characterized the genome sequences represented in two defective interfering particles derived from the heat-resistant strain of vesicular stomatitis virus by means of end-labeling and hybridization techniques. Both defective particle RNAs, which differ slightly in size, contain 5'-end sequences identical to each other and to that of the standard infectious virus genome, for at least the first approximately 55 bases. In contrast, the 3'-end sequences of these two RNAs are different. The 3'-end sequence of the smaller RNA is identical to that of the standard genome for at least the first 48 bases. The 3'-end sequence of the larger RNA is an inverted complement of its 5' end for approximately 65 bases. The bulk of the sequences in both RNAs is derived from the 3' half of the standard genome. We also show that the two defective particles differ in vitro transcription and in vivo replication properties. These results provide direct evidence for the presence of internal genome deletions in defective interfering particles of negative-stranded RNA animal viruses and demonstrate the existence of at least two distinct classes of these particles."}
{"id": "PMID:230502", "title": "Metal-coordinating substrate analogs as inhibitors of metalloenzymes.", "content": "A group of active-site metal coordinating inhibitors of zinc proteases (carboxypeptidase A, thermolysin, Bacillus cereus neutral protease, and angiotensin-converting enzyme) have been synthesized and their properties investigated. Their general structures are R-SH and R-NH-PO2(O phi)H, where-S- or -O- serve as metal ligands and R refers to an amino acid or peptide group designed to interact with substrate recognition sites. These inhibitors can be extremely potent; thus, N-(2-mercaptoacetyl)-D-phenylalanine, e.g., inhibits carboxypeptidase A with a Kiapp of 2.2 x 10(-7) M. The spectral response of cobalt(II)-substituted thermolysin or carboxypeptidase A to the sulfur-containing inhibitors signals the direct interaction of the mercaptan with the metal. An S leads to Co(II) charge transfer band is generated near 340 nm and is detected by absorption, circular dichroism, and magnetic circular dichroism. The cobalt(II) spectra indicate both inner sphere coordination with sulfur and 4-coordination in the enzyme-inhibitor complex. Thus, the metal undergoes a simple substitution reaction, the inhibitor most likely displacing water at the fourth coordination site.", "contents": "Metal-coordinating substrate analogs as inhibitors of metalloenzymes. A group of active-site metal coordinating inhibitors of zinc proteases (carboxypeptidase A, thermolysin, Bacillus cereus neutral protease, and angiotensin-converting enzyme) have been synthesized and their properties investigated. Their general structures are R-SH and R-NH-PO2(O phi)H, where-S- or -O- serve as metal ligands and R refers to an amino acid or peptide group designed to interact with substrate recognition sites. These inhibitors can be extremely potent; thus, N-(2-mercaptoacetyl)-D-phenylalanine, e.g., inhibits carboxypeptidase A with a Kiapp of 2.2 x 10(-7) M. The spectral response of cobalt(II)-substituted thermolysin or carboxypeptidase A to the sulfur-containing inhibitors signals the direct interaction of the mercaptan with the metal. An S leads to Co(II) charge transfer band is generated near 340 nm and is detected by absorption, circular dichroism, and magnetic circular dichroism. The cobalt(II) spectra indicate both inner sphere coordination with sulfur and 4-coordination in the enzyme-inhibitor complex. Thus, the metal undergoes a simple substitution reaction, the inhibitor most likely displacing water at the fourth coordination site."}
{"id": "PMID:230503", "title": "Prostaglandin D2, a neuromodulator.", "content": "The distribution of prostaglandin D synthetase activity was determined in various tissues of rat by using the supernatant fraction (10,000 x g, 20 min) of the homogenates. The highest activity was found in brain, spinal cord, and alimentary tract. The activity was uniquitously distributed in all parts of brain, and the highest specific activity was found in hypothalamus and thalamus. Homogenates of two neuroblastoma cell lines were found to produce prostaglandin D2, whereas a glioma cell line was almost inactive. Prostaglandin D2 is a potent and specific activator of the adenylate cyclase system of cultured neuroblastoma cells, suggesting the possibility that it may act as a neuromodulator in the central nervous system.", "contents": "Prostaglandin D2, a neuromodulator. The distribution of prostaglandin D synthetase activity was determined in various tissues of rat by using the supernatant fraction (10,000 x g, 20 min) of the homogenates. The highest activity was found in brain, spinal cord, and alimentary tract. The activity was uniquitously distributed in all parts of brain, and the highest specific activity was found in hypothalamus and thalamus. Homogenates of two neuroblastoma cell lines were found to produce prostaglandin D2, whereas a glioma cell line was almost inactive. Prostaglandin D2 is a potent and specific activator of the adenylate cyclase system of cultured neuroblastoma cells, suggesting the possibility that it may act as a neuromodulator in the central nervous system."}
{"id": "PMID:230504", "title": "Evidence that the avian sarcoma virus transforming gene product is a cyclic AMP-independent protein kinase.", "content": "The avian sarcoma virus transforming gene product pp60src has been partially purified by using ion exchange or immunoaffinity chromatography. These preparations contain a cyclic AMP-independent protein kinase activity capable of transferring radiolabel from [gamma-32P]ATP to immune rabbit IgG, casein, and the heavy chain purified from normal rabbit IgG. The casein kinase activity is specifically inhibited by anti-pp60src IgG. Comparison of the pp60src-protein kinase isolated from cells transformed by a wild-type ASV or by an ASV temperature-sensitive transformation mutant revealed that the latter product had a half-life of 3 min at 41 degrees C whereas that of the wild-type product was 20 min.", "contents": "Evidence that the avian sarcoma virus transforming gene product is a cyclic AMP-independent protein kinase. The avian sarcoma virus transforming gene product pp60src has been partially purified by using ion exchange or immunoaffinity chromatography. These preparations contain a cyclic AMP-independent protein kinase activity capable of transferring radiolabel from [gamma-32P]ATP to immune rabbit IgG, casein, and the heavy chain purified from normal rabbit IgG. The casein kinase activity is specifically inhibited by anti-pp60src IgG. Comparison of the pp60src-protein kinase isolated from cells transformed by a wild-type ASV or by an ASV temperature-sensitive transformation mutant revealed that the latter product had a half-life of 3 min at 41 degrees C whereas that of the wild-type product was 20 min."}
{"id": "PMID:230505", "title": "DNA gyrase: purification and catalytic properties of a fragment of gyrase B protein.", "content": "A protein isolated from Escherichia coli complements the DNA gyrase A (NalA) protein to generate an activity that relaxes supercoiled DNA. Oxolinic acid, a known inhibitor of DNA gyrase, blocks this activity and causes double-strand cleavage of DNA at the same sites as are attacked by DNA gyrase. The protein, of molecular weight 50,000, appears to be fragment of the DNA gyrase B (Cou) protein (molecular weight, 90,000) as judged by the identical sizes of numerous peptides produced by partial proteolytic digestion. The complex of this fragment and the gyrase A protein lacks both the DNA-supercoiling and DNA-dependent ATPase activities of DNA gyrase.", "contents": "DNA gyrase: purification and catalytic properties of a fragment of gyrase B protein. A protein isolated from Escherichia coli complements the DNA gyrase A (NalA) protein to generate an activity that relaxes supercoiled DNA. Oxolinic acid, a known inhibitor of DNA gyrase, blocks this activity and causes double-strand cleavage of DNA at the same sites as are attacked by DNA gyrase. The protein, of molecular weight 50,000, appears to be fragment of the DNA gyrase B (Cou) protein (molecular weight, 90,000) as judged by the identical sizes of numerous peptides produced by partial proteolytic digestion. The complex of this fragment and the gyrase A protein lacks both the DNA-supercoiling and DNA-dependent ATPase activities of DNA gyrase."}
{"id": "PMID:230506", "title": "Single-strand binding protein enhances fidelity of DNA synthesis in vitro.", "content": "The effect of Escherichia coli single-strand binding protein on the accuracy of in vitro DNA synthesis has been determined by using two independent methods. By using the synthetic polynucleotide poly[d(A-T)] and measuring dGTP misincorporation or by using phi X174 DNA and measuring nucleotide substitutions, we found that binding protein increases the fidelity of DNA synthesis by as much as 10-fold. This increase is observed with DNA polymerases of divergent sources and is progressive with increasing concentration of binding protein. The increased accuracy observed with DNA polymerases lacking a 3' leads to 5' exonuclease points to a mechanism other than augmented proofreading. In accord with the properties of single-strand binding proteins, it is suggested that increased fidelity is a result of enhanced base selection by the DNA polymerase, resulting from increased rigidity of the template due to its interaction with binding protein.", "contents": "Single-strand binding protein enhances fidelity of DNA synthesis in vitro. The effect of Escherichia coli single-strand binding protein on the accuracy of in vitro DNA synthesis has been determined by using two independent methods. By using the synthetic polynucleotide poly[d(A-T)] and measuring dGTP misincorporation or by using phi X174 DNA and measuring nucleotide substitutions, we found that binding protein increases the fidelity of DNA synthesis by as much as 10-fold. This increase is observed with DNA polymerases of divergent sources and is progressive with increasing concentration of binding protein. The increased accuracy observed with DNA polymerases lacking a 3' leads to 5' exonuclease points to a mechanism other than augmented proofreading. In accord with the properties of single-strand binding proteins, it is suggested that increased fidelity is a result of enhanced base selection by the DNA polymerase, resulting from increased rigidity of the template due to its interaction with binding protein."}
{"id": "PMID:230507", "title": "Enhanced phosphorylation of many endogenous protein substrates in human fibroblasts transformed by simian virus 40.", "content": "Protein phosphorylation in normal and in simian virus 40-transformed human skin fibroblasts was assessed by two different methods: incubation of whole-cell homogenates with [gamma-(32)P]ATP or labeling of intact cells with Na(2)H(32)PO(4). Phosphorylated proteins were detected by sodium dodecyl sulfate/polyacrylamide gel electrophoresis and autoradiography. With both methods, the Coomassie-blue-stained protein patterns of the three transformed cell lines studied were similar to the patterns of the nontransformed normal human cells. However, although the phosphoprotein autoradiograms of the three transformed cell lines were nearly identical, their patterns were strikingly different from those of the nontransformed cells. Each of the three transformed lines tested showed approximately 25-30 phosphoprotein bands that were significantly enhanced when compared to the patterns of the nontransformed cells. Quantitation of 12 of the enhanced phosphoprotein bands in one of the transformed cell lines showed an average of 4.4 times as much phosphorylation as in the normal cells. The enhanced phosphorylation observed in the transformed cell lines was not dependent on the growth rate of the cells or on cyclic AMP. Furthermore, when homogenates of transformed and nontransformed cells were mixed prior to incubation with [gamma-(32)P]ATP, the resultant phosphoprotein patterns resembed those obtained with transformed cells alone. In addition, an evaluation of the time course of protein phosphorylation revealed that the initial reaction rate was greater in the transformed than in the normal cells, although in both cell types the reaction was complete after 1 min. The results suggest that the simian virus 40-transformed human fibroblasts possess an increased ability to phosphorylate proteins rather than that the normal cells possess a diffusible inhibitor. There appear to be many endogenous cellular substrates for this increased activity.", "contents": "Enhanced phosphorylation of many endogenous protein substrates in human fibroblasts transformed by simian virus 40. Protein phosphorylation in normal and in simian virus 40-transformed human skin fibroblasts was assessed by two different methods: incubation of whole-cell homogenates with [gamma-(32)P]ATP or labeling of intact cells with Na(2)H(32)PO(4). Phosphorylated proteins were detected by sodium dodecyl sulfate/polyacrylamide gel electrophoresis and autoradiography. With both methods, the Coomassie-blue-stained protein patterns of the three transformed cell lines studied were similar to the patterns of the nontransformed normal human cells. However, although the phosphoprotein autoradiograms of the three transformed cell lines were nearly identical, their patterns were strikingly different from those of the nontransformed cells. Each of the three transformed lines tested showed approximately 25-30 phosphoprotein bands that were significantly enhanced when compared to the patterns of the nontransformed cells. Quantitation of 12 of the enhanced phosphoprotein bands in one of the transformed cell lines showed an average of 4.4 times as much phosphorylation as in the normal cells. The enhanced phosphorylation observed in the transformed cell lines was not dependent on the growth rate of the cells or on cyclic AMP. Furthermore, when homogenates of transformed and nontransformed cells were mixed prior to incubation with [gamma-(32)P]ATP, the resultant phosphoprotein patterns resembed those obtained with transformed cells alone. In addition, an evaluation of the time course of protein phosphorylation revealed that the initial reaction rate was greater in the transformed than in the normal cells, although in both cell types the reaction was complete after 1 min. The results suggest that the simian virus 40-transformed human fibroblasts possess an increased ability to phosphorylate proteins rather than that the normal cells possess a diffusible inhibitor. There appear to be many endogenous cellular substrates for this increased activity."}
{"id": "PMID:230508", "title": "Identification of transferrin receptors on the surface of human cultured cells.", "content": "We have examined the binding of human transferrin to cultured human choriocarcinoma cell lines and to detergent extracts of such cells. The results indicate the presence of a high-affinity saturable binding site (Ka = 4.25 x 10(8) M-1) that is specific for transferrin. This receptor has also been detected on three other human cell lines of different phenotypic origin, including Wil-2 (splenic lymphocytes of B-cell origin), RPMI-2650 (a quasi-diploid nasopharyngeal carcinoma), and WI-38 (embryonic lung fibroblasts). By using anti-human transferrin antiserum to immunoprecipitate the receptor-transferrin complex from detergent extracts of cells containing saturating levels of transferrin followed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis, a single polypeptide of 90,000 daltons has been identified as a subunit of the putative transferrin receptor. The protein shows immunochemical identity and coelectrophoreses in sodium dodecyl sulfate gels with a cell surface glycoprotein subunit, previously identified in placental brush border membrane preparations, on all human cultured cell lines examined. These results suggest that the recent demonstration of transferrin dependence of maximal cell growth in culture [e.g., Hutchings, S.E. & Sato, G.H. (1978) Proc. Natl. Acad. Sci. USA 75, 901-904] is mediated through expression of this glycoprotein receptor.", "contents": "Identification of transferrin receptors on the surface of human cultured cells. We have examined the binding of human transferrin to cultured human choriocarcinoma cell lines and to detergent extracts of such cells. The results indicate the presence of a high-affinity saturable binding site (Ka = 4.25 x 10(8) M-1) that is specific for transferrin. This receptor has also been detected on three other human cell lines of different phenotypic origin, including Wil-2 (splenic lymphocytes of B-cell origin), RPMI-2650 (a quasi-diploid nasopharyngeal carcinoma), and WI-38 (embryonic lung fibroblasts). By using anti-human transferrin antiserum to immunoprecipitate the receptor-transferrin complex from detergent extracts of cells containing saturating levels of transferrin followed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis, a single polypeptide of 90,000 daltons has been identified as a subunit of the putative transferrin receptor. The protein shows immunochemical identity and coelectrophoreses in sodium dodecyl sulfate gels with a cell surface glycoprotein subunit, previously identified in placental brush border membrane preparations, on all human cultured cell lines examined. These results suggest that the recent demonstration of transferrin dependence of maximal cell growth in culture [e.g., Hutchings, S.E. & Sato, G.H. (1978) Proc. Natl. Acad. Sci. USA 75, 901-904] is mediated through expression of this glycoprotein receptor."}
{"id": "PMID:230509", "title": "Induction of erythroid differentiation of murine erythroleukemia cells by nicotinamide and related compounds.", "content": "Nicotinamide and its analogues were evaluated for their activity as inducers of differentiation of murine erythroleukemia cells in culture. N'-Methylnicotinamide was the most effective of the compounds tested; at its optimal concentration it was more effective than dimethyl sulfoxide. With 8-10 mM N'-methylnicotinamide, almost all the cells contained hemoglobin (benzidine-reactive) after a 60-hr culture. Commitment to differentiate, assayed by transfer of the cells to semisolid medium without inducers, occurred much earlier and was more extensive with N'-methylnicotinamide than that with dimethyl sulfoxide or nicotinamide. Increase in globin mRNA was greater in the cells cultured with N'-methylnicotinamide than in cells cultured with dimethyl sulfoxide or nicotinamide. The relationship between the inducing activities of nicotinamide analogues and their effect on poly(ADP-ribose) polymerase in vitro was studied. All the compounds studied that had strong inhibitory effects on poly(ADP-ribose) polymerase in vitro induced differentiation of erythroleukemia cells in culture. This property is not a prerequisite of inducers; N'-methylnicotinamide did not inhibit the enzyme in vitro.", "contents": "Induction of erythroid differentiation of murine erythroleukemia cells by nicotinamide and related compounds. Nicotinamide and its analogues were evaluated for their activity as inducers of differentiation of murine erythroleukemia cells in culture. N'-Methylnicotinamide was the most effective of the compounds tested; at its optimal concentration it was more effective than dimethyl sulfoxide. With 8-10 mM N'-methylnicotinamide, almost all the cells contained hemoglobin (benzidine-reactive) after a 60-hr culture. Commitment to differentiate, assayed by transfer of the cells to semisolid medium without inducers, occurred much earlier and was more extensive with N'-methylnicotinamide than that with dimethyl sulfoxide or nicotinamide. Increase in globin mRNA was greater in the cells cultured with N'-methylnicotinamide than in cells cultured with dimethyl sulfoxide or nicotinamide. The relationship between the inducing activities of nicotinamide analogues and their effect on poly(ADP-ribose) polymerase in vitro was studied. All the compounds studied that had strong inhibitory effects on poly(ADP-ribose) polymerase in vitro induced differentiation of erythroleukemia cells in culture. This property is not a prerequisite of inducers; N'-methylnicotinamide did not inhibit the enzyme in vitro."}
{"id": "PMID:230510", "title": "Polarity of influenza and vesicular stomatitis virus maturation in MDCK cells: lack of a requirement for glycosylation of viral glycoproteins.", "content": "We have investigated whether glycosylation of membrane glycoproteins is a determinant of the site of maturation of enveloped viruses in Madin-Darby canine kidney (MDCK) cells. In MDCK cell monolayers, vesicular stomatitis virus buds exclusively from the basal or lateral plasma membranes and contains a sialylated glycoprotein, whereas influenza virus buds exclusively from the apical plasma membrane and lacks neuraminic acid. In order to study the possible relationship between glycosylation of viral glycoproteins and the budding site, infected MDCK cells were treated with tunicamycin at a concentration that completely inhibits glycosylation of viral glycoproteins and the site of virus maturation was examined by electron microscopy. When tunicamycin-treated monolayers were compared to controls, the polarity in the maturation sites of both viruses was maintained. These results indicate that glycosylation of viral glycoproteins is not required for the determination of the cellular maturation site of these enveloped viruses.", "contents": "Polarity of influenza and vesicular stomatitis virus maturation in MDCK cells: lack of a requirement for glycosylation of viral glycoproteins. We have investigated whether glycosylation of membrane glycoproteins is a determinant of the site of maturation of enveloped viruses in Madin-Darby canine kidney (MDCK) cells. In MDCK cell monolayers, vesicular stomatitis virus buds exclusively from the basal or lateral plasma membranes and contains a sialylated glycoprotein, whereas influenza virus buds exclusively from the apical plasma membrane and lacks neuraminic acid. In order to study the possible relationship between glycosylation of viral glycoproteins and the budding site, infected MDCK cells were treated with tunicamycin at a concentration that completely inhibits glycosylation of viral glycoproteins and the site of virus maturation was examined by electron microscopy. When tunicamycin-treated monolayers were compared to controls, the polarity in the maturation sites of both viruses was maintained. These results indicate that glycosylation of viral glycoproteins is not required for the determination of the cellular maturation site of these enveloped viruses."}
{"id": "PMID:230511", "title": "Microenvironmental influences on the in vivo behavior of neoplastic lymphocytes.", "content": "A transplantable hamster lymphocytic neoplasma of probable monoclonal derivation, induced by the oncogenic DNA simian virus 40, has been adapted to grow in the allogeneic host either as leukemia (characterized by dissemination and poor prognosis) or as lymphoma (characterized by localization and favorable prognosis) [Diamandopoulos, G. Th. (1978) Proc. Natl. Acad. Sci. USA 75, 2011-2015]. In the present experiments the circumstances under which neoplastic lymphocytes that are transplanted in allogeneic animals retain, lose, or regain the capacity for dissemination or localization are assessed. Results indicate that the in vivo behavior of neoplastic lymphocytes is not a stable, irreversible characteristic that is transmitted to the cell progeny. On the contrary, it can be altered by the origin/tissue microenvironment in which the cells proliferate. It is suggested that, whereas neoplastic cell mutation followed by host selection could be responsible for changes in cell behavior, a more likely explanation is that the proliferating neoplastic lymphocytes acquire reversible nonmutational phenotypic characteristics during their interaction with the host microenvironment, which modify their behavior and, as a result, the prognosis of the neoplastic process.", "contents": "Microenvironmental influences on the in vivo behavior of neoplastic lymphocytes. A transplantable hamster lymphocytic neoplasma of probable monoclonal derivation, induced by the oncogenic DNA simian virus 40, has been adapted to grow in the allogeneic host either as leukemia (characterized by dissemination and poor prognosis) or as lymphoma (characterized by localization and favorable prognosis) [Diamandopoulos, G. Th. (1978) Proc. Natl. Acad. Sci. USA 75, 2011-2015]. In the present experiments the circumstances under which neoplastic lymphocytes that are transplanted in allogeneic animals retain, lose, or regain the capacity for dissemination or localization are assessed. Results indicate that the in vivo behavior of neoplastic lymphocytes is not a stable, irreversible characteristic that is transmitted to the cell progeny. On the contrary, it can be altered by the origin/tissue microenvironment in which the cells proliferate. It is suggested that, whereas neoplastic cell mutation followed by host selection could be responsible for changes in cell behavior, a more likely explanation is that the proliferating neoplastic lymphocytes acquire reversible nonmutational phenotypic characteristics during their interaction with the host microenvironment, which modify their behavior and, as a result, the prognosis of the neoplastic process."}
{"id": "PMID:230512", "title": "Chromosome 1 contains the endogenous RAV-0 retrovirus sequences in chicken cells.", "content": "We have developed a structurally unique probe which can be used to determine the chromosomal location of nonreiterated genes in vertebrate organisms by the method of in situ hybridization. The probe consists of several specific RNA molecules attached by means of poly(A) . poly(BrdUrd) hybrids to 125I-labeled DNA of high molecular weight. The probe can be synthesized with a variety of RNA molecules, giving it versatility for detecting a variety of genes irrespective of gene size, copy frequency, and host genome complexity. Using this probe prepared with retrovirus genomic RNAs, we have physically mapped all three detectable endogenous genomes of Rous-associated virus type 0 (RAV-0) in Spafas gs- chf- (group-specific antigen negative, chicken helper factor negative) chicken fibroblasts to specific sites on chromosome 1. This finding suggests that these multiple nontranscribed RAV-0 genomes evolved through gene duplication of an original RAV-0 genome. The endogenous src gene coding for a 60,000-dalton protein also has been localized to one of the small macrochromosomes, 10, 11, or 12, in both chicken and Japanese quail cells. The results presented here are consistent with and greatly extend previously reported data obtained by using both chromosome fractionation and restriction endonuclease techniques and thus support the soundness of this hybridization approach.", "contents": "Chromosome 1 contains the endogenous RAV-0 retrovirus sequences in chicken cells. We have developed a structurally unique probe which can be used to determine the chromosomal location of nonreiterated genes in vertebrate organisms by the method of in situ hybridization. The probe consists of several specific RNA molecules attached by means of poly(A) . poly(BrdUrd) hybrids to 125I-labeled DNA of high molecular weight. The probe can be synthesized with a variety of RNA molecules, giving it versatility for detecting a variety of genes irrespective of gene size, copy frequency, and host genome complexity. Using this probe prepared with retrovirus genomic RNAs, we have physically mapped all three detectable endogenous genomes of Rous-associated virus type 0 (RAV-0) in Spafas gs- chf- (group-specific antigen negative, chicken helper factor negative) chicken fibroblasts to specific sites on chromosome 1. This finding suggests that these multiple nontranscribed RAV-0 genomes evolved through gene duplication of an original RAV-0 genome. The endogenous src gene coding for a 60,000-dalton protein also has been localized to one of the small macrochromosomes, 10, 11, or 12, in both chicken and Japanese quail cells. The results presented here are consistent with and greatly extend previously reported data obtained by using both chromosome fractionation and restriction endonuclease techniques and thus support the soundness of this hybridization approach."}
{"id": "PMID:230513", "title": "Five TGA \"stop\" codons occur within the translated sequence of the yeast mitochondrial gene for cytochrome c oxidase subunit II.", "content": "A mitochondrial mutation that genetically maps in the middle of the gene coding cytochrome c oxidase subunit II has been found to be a single-base-pair deletion. Three independently isolated spontaneous revertants of this mutant have different single-base-pair insertions within 15 nucleotides of the mutation. These findings clearly identify the location of the gene and suggest that the mutation causes a frame-shift. The sequence of about 900 base pairs surrounding the mutation has been determined and found to have several chain termination codons in every possible reading frame. The sequence can, however, be translated in one frame by assuming that the codon TGA does not cause chain termination in yeast mitochondira, as was recently suggested for the human organelle [Barrell, B. G., Bankier, A. T. & Drouin, J. (1979) Nature (London), in press]. If TGA codes for tryptophan residues, as is apparently the case in human mitochondria, a polypeptide can be read from the yeast mtDNA that is identical to bovine cytochrome oxidase subunit II at 37.8% of its residues. Furthermore, the DNA sequences of the frame-shift revertants discussed above predict relative isolectric point differences between the wild-type and various revertant forms of the polypeptide. The detection of these isolectric point differences by two-dimensional electrophoresis of subunit II from the various strains independently confirms the presumed reading frame of the gene. It is concluded that TGA is translated in yeast mitochondria, most probably as tryptophan.", "contents": "Five TGA \"stop\" codons occur within the translated sequence of the yeast mitochondrial gene for cytochrome c oxidase subunit II. A mitochondrial mutation that genetically maps in the middle of the gene coding cytochrome c oxidase subunit II has been found to be a single-base-pair deletion. Three independently isolated spontaneous revertants of this mutant have different single-base-pair insertions within 15 nucleotides of the mutation. These findings clearly identify the location of the gene and suggest that the mutation causes a frame-shift. The sequence of about 900 base pairs surrounding the mutation has been determined and found to have several chain termination codons in every possible reading frame. The sequence can, however, be translated in one frame by assuming that the codon TGA does not cause chain termination in yeast mitochondira, as was recently suggested for the human organelle [Barrell, B. G., Bankier, A. T. & Drouin, J. (1979) Nature (London), in press]. If TGA codes for tryptophan residues, as is apparently the case in human mitochondria, a polypeptide can be read from the yeast mtDNA that is identical to bovine cytochrome oxidase subunit II at 37.8% of its residues. Furthermore, the DNA sequences of the frame-shift revertants discussed above predict relative isolectric point differences between the wild-type and various revertant forms of the polypeptide. The detection of these isolectric point differences by two-dimensional electrophoresis of subunit II from the various strains independently confirms the presumed reading frame of the gene. It is concluded that TGA is translated in yeast mitochondria, most probably as tryptophan."}
{"id": "PMID:230514", "title": "Inhibition of cis-platinum nephrotoxicity by diethyldithiocarbamate rescue in a rat model.", "content": "The nephrotoxic effects of cis-dichlorodiammineplatinum(II) (NSC-119875) administered to male F344 rats at the median lethal dose (LD50; 7.5 mg/kg) were inhibited by treatment with sodium diethyldithiocarbamate (500 or 750 mg/kg) between 1 and 4 hr after cis-platinum administration. Those animals receiving cis-platinum alone had mean serum blood urea nitrogen levels of 234 mg/dl at the time of maximal toxicity (day 5); kidney sections revealed large areas of degeneration and necrosis. When dithiocarbamate rescue was carried out after cis-platinum treatment, mean blood urea nitrogen levels were in the range 56-95 mg/dl; kidney sections were grossly normal with a barely discernible band of degeneration at the corticomedullary junction. Gastrointestinal toxicity was observed in greater than 95% of the cis-platinum-treated rats but was totally absent in those receiving subsequent rescue treatment. A significant decrease in weight loss was also observed in the dithiocarbamate-rescued rats. Based on the chemistry of platinum-sulfur interactions and the observed time-dependence of the rescue treatment, it is suggested that dithiocarbamate exerts its effects via competitive chelation and removal of platinum coordinated to protein-bound sulfhydryl groups of the kidney tubule cells.", "contents": "Inhibition of cis-platinum nephrotoxicity by diethyldithiocarbamate rescue in a rat model. The nephrotoxic effects of cis-dichlorodiammineplatinum(II) (NSC-119875) administered to male F344 rats at the median lethal dose (LD50; 7.5 mg/kg) were inhibited by treatment with sodium diethyldithiocarbamate (500 or 750 mg/kg) between 1 and 4 hr after cis-platinum administration. Those animals receiving cis-platinum alone had mean serum blood urea nitrogen levels of 234 mg/dl at the time of maximal toxicity (day 5); kidney sections revealed large areas of degeneration and necrosis. When dithiocarbamate rescue was carried out after cis-platinum treatment, mean blood urea nitrogen levels were in the range 56-95 mg/dl; kidney sections were grossly normal with a barely discernible band of degeneration at the corticomedullary junction. Gastrointestinal toxicity was observed in greater than 95% of the cis-platinum-treated rats but was totally absent in those receiving subsequent rescue treatment. A significant decrease in weight loss was also observed in the dithiocarbamate-rescued rats. Based on the chemistry of platinum-sulfur interactions and the observed time-dependence of the rescue treatment, it is suggested that dithiocarbamate exerts its effects via competitive chelation and removal of platinum coordinated to protein-bound sulfhydryl groups of the kidney tubule cells."}
{"id": "PMID:230515", "title": "Defect in 3'-phosphoadenosine 5'-phosphosulfate formation in brachymorphic mice.", "content": "Incorporation of 35SO42- into adenosine 5'-phosphosulfate (APS), 3'-phosphoadenosine 5'-phosphosulfate (PAPS), and chondroitin sulfate was simultaneously assessed with extracts prepared from epiphyseal cartilage of neonatal normal or homozygous brachymorphic mice. Radioactivity measured in APS, PAPS, and chondroitin sulfate of extracts from brachymorphic cartilage was approximately 300%, 9%, and 13% of the normal levels, respectively. Even though more APS accumulated in the mutant cartilage extracts, APS actually synthesized (total 35SO42- incorporated into APS, PAPS, and macromolecular products) was only 17% of that in the normal. However, of the amount synthesized, 90% and 55% of newly synthesized APS were converted to PAPS by cartilage extracts of normal and brachymorphic mice, respectively. Specific assays for ATP sulfurylase (sulfate adenylyltransferase; ATP:sulfate adenylyltransferase, EC 2.7.7.4) and APS kinase (adenylylsulfate kinase; ATP:adenylylsulfate 3'-phosphotransferase, EC 2.7.1.25) showed that the sulfurylase enzyme activity is reduced to approximately 1/2 and the kinase to approxomately 1/14 in brachymorphic mice. These results suggest that the production of an undersulfated proteoglycan in brachymorphic cartilage results from a defective conversion of APS to PAPS.", "contents": "Defect in 3'-phosphoadenosine 5'-phosphosulfate formation in brachymorphic mice. Incorporation of 35SO42- into adenosine 5'-phosphosulfate (APS), 3'-phosphoadenosine 5'-phosphosulfate (PAPS), and chondroitin sulfate was simultaneously assessed with extracts prepared from epiphyseal cartilage of neonatal normal or homozygous brachymorphic mice. Radioactivity measured in APS, PAPS, and chondroitin sulfate of extracts from brachymorphic cartilage was approximately 300%, 9%, and 13% of the normal levels, respectively. Even though more APS accumulated in the mutant cartilage extracts, APS actually synthesized (total 35SO42- incorporated into APS, PAPS, and macromolecular products) was only 17% of that in the normal. However, of the amount synthesized, 90% and 55% of newly synthesized APS were converted to PAPS by cartilage extracts of normal and brachymorphic mice, respectively. Specific assays for ATP sulfurylase (sulfate adenylyltransferase; ATP:sulfate adenylyltransferase, EC 2.7.7.4) and APS kinase (adenylylsulfate kinase; ATP:adenylylsulfate 3'-phosphotransferase, EC 2.7.1.25) showed that the sulfurylase enzyme activity is reduced to approximately 1/2 and the kinase to approxomately 1/14 in brachymorphic mice. These results suggest that the production of an undersulfated proteoglycan in brachymorphic cartilage results from a defective conversion of APS to PAPS."}
{"id": "PMID:230516", "title": "Production of choriogonadotropin-like factor by a microorganism.", "content": "Extracts from an acetone powder preparation of a culture of a microorganism tentatively named Progenitor cryptocides contain choriogonadotropin (CG)-like factor as determined by radioimmunoassay with antiserum to human (h)CG beta subunit COOH-terminal peptide and radioreceptor assay with bovine corpus luteum membranes. Possible interference by proteases in the extracts was excluded. Immunoreactive materials reacting with antisera to hCG beta subunit and hCG beta subunit COOH-terminal peptide were also found in the extracts. No free alpha subunit was detected. The CG-like factor was purified by chromatography on Sephadex G-100, concanavalin A-Sepharose, and DEAE-Sephadex A-50. The factor was adsorbed by concanavalin A-Sepharose, suggesting that it contains mannose and glucose moieties. The factor was eluted at the same position as standard hCG on Sephadex G-100. It dissociated into two bands when subjected to sodium dodecyl sulfate/polyacrylamide gel electrophoresis; the bands corresponded to the respective standard hCG subunits. The biological activity of the purified factor as determined by the rat uterine weight assay and the ovarian weight assay was equivalent to 380 (95% confidence limits: 320-490) and 880 (780-1020) international units/mg, respectively. It can be concluded from the present results that a microorganism produces a glycoprotein that is biologically active and has physicochemical properties similar to those of hCG.", "contents": "Production of choriogonadotropin-like factor by a microorganism. Extracts from an acetone powder preparation of a culture of a microorganism tentatively named Progenitor cryptocides contain choriogonadotropin (CG)-like factor as determined by radioimmunoassay with antiserum to human (h)CG beta subunit COOH-terminal peptide and radioreceptor assay with bovine corpus luteum membranes. Possible interference by proteases in the extracts was excluded. Immunoreactive materials reacting with antisera to hCG beta subunit and hCG beta subunit COOH-terminal peptide were also found in the extracts. No free alpha subunit was detected. The CG-like factor was purified by chromatography on Sephadex G-100, concanavalin A-Sepharose, and DEAE-Sephadex A-50. The factor was adsorbed by concanavalin A-Sepharose, suggesting that it contains mannose and glucose moieties. The factor was eluted at the same position as standard hCG on Sephadex G-100. It dissociated into two bands when subjected to sodium dodecyl sulfate/polyacrylamide gel electrophoresis; the bands corresponded to the respective standard hCG subunits. The biological activity of the purified factor as determined by the rat uterine weight assay and the ovarian weight assay was equivalent to 380 (95% confidence limits: 320-490) and 880 (780-1020) international units/mg, respectively. It can be concluded from the present results that a microorganism produces a glycoprotein that is biologically active and has physicochemical properties similar to those of hCG."}
{"id": "PMID:230517", "title": "Human cell lines containing Epstein-Barr virus but distinct from the common B cell lymphoblastoid lines.", "content": "A group of very similar cell lines was established from peripheral blood or bone marrow of 12 patients with a variety of disorders. The cells in these cell lines were uniform and round in shape. They grew as single-cell suspensions or as aggregates of small numbers of cells in stationary culture. The most striking characteristic of these lines was the lack of cells with surface immunoglobulin or with demonstrable immunoglobulin synthesis. This lack of immunoglobulin synthesis and their special growth characteristics distinguished them from the lymphoblastoid B cell lines previously described. The cells of these unusual cell lines had strong Fc receptors and C3 receptors and expressed Ia antigens. They did not form rosettes with sheep erythrocytes and did not have detectable levels of terminal deoxynucleotidyltransferase. They did not secrete lysozyme and failed to stain for peroxidase. The presence of the Epstein-Barr virus nuclear antigen in the cells indicated the presence of Epstein-Barr viral genome. The possibility that these cells represent some type of precursor cell in the B cell lineage is discussed, but the exact cellular origin remains to be ascertained.", "contents": "Human cell lines containing Epstein-Barr virus but distinct from the common B cell lymphoblastoid lines. A group of very similar cell lines was established from peripheral blood or bone marrow of 12 patients with a variety of disorders. The cells in these cell lines were uniform and round in shape. They grew as single-cell suspensions or as aggregates of small numbers of cells in stationary culture. The most striking characteristic of these lines was the lack of cells with surface immunoglobulin or with demonstrable immunoglobulin synthesis. This lack of immunoglobulin synthesis and their special growth characteristics distinguished them from the lymphoblastoid B cell lines previously described. The cells of these unusual cell lines had strong Fc receptors and C3 receptors and expressed Ia antigens. They did not form rosettes with sheep erythrocytes and did not have detectable levels of terminal deoxynucleotidyltransferase. They did not secrete lysozyme and failed to stain for peroxidase. The presence of the Epstein-Barr virus nuclear antigen in the cells indicated the presence of Epstein-Barr viral genome. The possibility that these cells represent some type of precursor cell in the B cell lineage is discussed, but the exact cellular origin remains to be ascertained."}
{"id": "PMID:230518", "title": "Immunofluorescent localization of angiotensin converting enzyme in epithelioid and giant cells of sarcoidosis granulomas.", "content": "Angiotensin converting enzyme (ACE) (dipeptidyl carboxypeptidase; peptidyldipeptide hydrolase, EC 3.4.15.1) was localized in epithelioid and giant cells within ACE-rich sarcoidosis granulomas, but not control granulomas, by immunofluorescence by using a rabbit anti-human ACE immunoglobulin for localization and fluorescein-labeled goat anti-rabbit immunoglobulin for detection. ACE was frequently not detected in the very central epithelioid cells, perhaps due to a paucity of cellular or molecular stimulatory interaction in this region. The results suggest that marked elevation of ACE in the granulomas and often in the serum in sarcoidosis may be due to intense induction of ACE in most epithelioid and giant cells of the sarcoidosis granulomas.", "contents": "Immunofluorescent localization of angiotensin converting enzyme in epithelioid and giant cells of sarcoidosis granulomas. Angiotensin converting enzyme (ACE) (dipeptidyl carboxypeptidase; peptidyldipeptide hydrolase, EC 3.4.15.1) was localized in epithelioid and giant cells within ACE-rich sarcoidosis granulomas, but not control granulomas, by immunofluorescence by using a rabbit anti-human ACE immunoglobulin for localization and fluorescein-labeled goat anti-rabbit immunoglobulin for detection. ACE was frequently not detected in the very central epithelioid cells, perhaps due to a paucity of cellular or molecular stimulatory interaction in this region. The results suggest that marked elevation of ACE in the granulomas and often in the serum in sarcoidosis may be due to intense induction of ACE in most epithelioid and giant cells of the sarcoidosis granulomas."}
{"id": "PMID:230519", "title": "Dynorphin-(1-13), an extraordinarily potent opioid peptide.", "content": "We describe the opioid properties of a tridecapeptide, the sequence of which corresponds to the NH2-terminal sequence of dynorphin, a novel porcine pituitary endorphin. It contains [Leu]enkephalin. In the guinea pig ileum longitudinal muscle preparation it is about 700 times more potent than [Leu]enkephalin. Its effects in this tissue are blocked completely by naloxone, but the apparent affinity of naloxone is 1/13th that for blockade of [Leu]enkephalin or normorphine. In the mouse vas deferens, this peptide is 3 times more potent than [Leu]enkephalin. Well-washed rat brain membranes degrade the peptide rapidly, suggesting the presence of a membrane-bound degradative enzyme. The peptide displays considerable immunoreactivity in assays with antisera that have been used for the immunohistochemical localization of [Leu]enkephalin. The remarkable enhancement of the potency of [Leu]enkephalin by the COOH-terminal extension -Arg-Arg-Ile-Arg-Pro-Lys-Leu-Lys-OH suggests new interpretations concerning the structure of opiate receptors and the function of the enkephalin pentapeptides.", "contents": "Dynorphin-(1-13), an extraordinarily potent opioid peptide. We describe the opioid properties of a tridecapeptide, the sequence of which corresponds to the NH2-terminal sequence of dynorphin, a novel porcine pituitary endorphin. It contains [Leu]enkephalin. In the guinea pig ileum longitudinal muscle preparation it is about 700 times more potent than [Leu]enkephalin. Its effects in this tissue are blocked completely by naloxone, but the apparent affinity of naloxone is 1/13th that for blockade of [Leu]enkephalin or normorphine. In the mouse vas deferens, this peptide is 3 times more potent than [Leu]enkephalin. Well-washed rat brain membranes degrade the peptide rapidly, suggesting the presence of a membrane-bound degradative enzyme. The peptide displays considerable immunoreactivity in assays with antisera that have been used for the immunohistochemical localization of [Leu]enkephalin. The remarkable enhancement of the potency of [Leu]enkephalin by the COOH-terminal extension -Arg-Arg-Ile-Arg-Pro-Lys-Leu-Lys-OH suggests new interpretations concerning the structure of opiate receptors and the function of the enkephalin pentapeptides."}
{"id": "PMID:230523", "title": "Comparison of the effects of ouabain and high tissue sodium on the calcium pools involved in excitation-contraction coupling.", "content": "According to one hypothesis for the mechanism of action of cardiac glycosides, inhibition of cardiac Na,K-ATPase elevates [Na]i and by increasing Na:Ca exchange, increases [Ca]i to ultimately produce the positive inotropic effect (PIE). Therapeutic concentrations of ouabain specifically increase the Ca content of a superficial pool involved in excitation-contraction coupling. Thus, for this hypothesis to be correct, equivalent increases in total Na by means other than Na,K-ATPase inhibition must also specifically increase the Ca content of this pool and produce a PIE. However, unlike the effects produced by ouabain, contracture, an elevation of tissue K and a nonspecific increase in Ca uptake occurred in Na-loaded hearts. Although Na loading and ouabain treatment increased total tissue Na to the same extent, the results suggest that (a) the increased tissue Na may not reflect an equivalent increase in [Na]i; (b) the Na-loading procedure was not a valid model for Na,K-ATPase inhibition, or (c) the hypothesis for cardiac glycoside action is incorrect.", "contents": "Comparison of the effects of ouabain and high tissue sodium on the calcium pools involved in excitation-contraction coupling. According to one hypothesis for the mechanism of action of cardiac glycosides, inhibition of cardiac Na,K-ATPase elevates [Na]i and by increasing Na:Ca exchange, increases [Ca]i to ultimately produce the positive inotropic effect (PIE). Therapeutic concentrations of ouabain specifically increase the Ca content of a superficial pool involved in excitation-contraction coupling. Thus, for this hypothesis to be correct, equivalent increases in total Na by means other than Na,K-ATPase inhibition must also specifically increase the Ca content of this pool and produce a PIE. However, unlike the effects produced by ouabain, contracture, an elevation of tissue K and a nonspecific increase in Ca uptake occurred in Na-loaded hearts. Although Na loading and ouabain treatment increased total tissue Na to the same extent, the results suggest that (a) the increased tissue Na may not reflect an equivalent increase in [Na]i; (b) the Na-loading procedure was not a valid model for Na,K-ATPase inhibition, or (c) the hypothesis for cardiac glycoside action is incorrect."}
{"id": "PMID:230526", "title": "Selective deprivation of paradoxical sleep and consolidation of shuttle-box avoidance.", "content": "Investigated whether paradoxical sleep is implicated in the storage of information acquired during shuttle-box avoidance. Wistar rats were given 5 brief training sessions distributed over the light period of the diurnal cycle. During the intervals between sessions the animals were selectively deprived of paradoxical sleep by awakening them every time they showed this type of sleep. The onset of paradoxical sleep was identified when hippocampal theta rhythm occurred during behavioural sleep. Yoked control animals got the same treatment irrespective of their sleep-waking behaviour, whereas free sleep rats were allowed to sleep undisturbed. In spite of large differences in the amount of paradoxical sleep during the intersession intervals no differences in learning performances were found among the groups. A tendency toward more intertrial crossings was noted in the paradoxical sleep deprived group at the end of training. It is concluded that storage of information acquired during distributed shuttle-box avoidance is not dependent on the presence of paradoxical sleep immediately following learning. Some possibilities are considered that paradoxical sleep may still be involved in memory storage processes.", "contents": "Selective deprivation of paradoxical sleep and consolidation of shuttle-box avoidance. Investigated whether paradoxical sleep is implicated in the storage of information acquired during shuttle-box avoidance. Wistar rats were given 5 brief training sessions distributed over the light period of the diurnal cycle. During the intervals between sessions the animals were selectively deprived of paradoxical sleep by awakening them every time they showed this type of sleep. The onset of paradoxical sleep was identified when hippocampal theta rhythm occurred during behavioural sleep. Yoked control animals got the same treatment irrespective of their sleep-waking behaviour, whereas free sleep rats were allowed to sleep undisturbed. In spite of large differences in the amount of paradoxical sleep during the intersession intervals no differences in learning performances were found among the groups. A tendency toward more intertrial crossings was noted in the paradoxical sleep deprived group at the end of training. It is concluded that storage of information acquired during distributed shuttle-box avoidance is not dependent on the presence of paradoxical sleep immediately following learning. Some possibilities are considered that paradoxical sleep may still be involved in memory storage processes."}
{"id": "PMID:230527", "title": "REM sleep deprivation increases preference for novelty in rats.", "content": "As a further test of the hypothesis that REM deprivation decreases fear, the behavior of 40 male rats was measured in a Y-maze adapted to test for preference for novelty. Prior to this test, the animals were exposed for 4 days to one of four treatments, i.e., either a dry environment control, a wet environment control, a 2-day REM deprivation period or a 4-day REM deprivation period. During the test both number of grid crossing in the novel and non-novel arms of the Y-maze and three indices of emotionality were recorded. The results were congruent with data we had reported earlier and offered convincing evidence in support of the hypothesis.", "contents": "REM sleep deprivation increases preference for novelty in rats. As a further test of the hypothesis that REM deprivation decreases fear, the behavior of 40 male rats was measured in a Y-maze adapted to test for preference for novelty. Prior to this test, the animals were exposed for 4 days to one of four treatments, i.e., either a dry environment control, a wet environment control, a 2-day REM deprivation period or a 4-day REM deprivation period. During the test both number of grid crossing in the novel and non-novel arms of the Y-maze and three indices of emotionality were recorded. The results were congruent with data we had reported earlier and offered convincing evidence in support of the hypothesis."}
{"id": "PMID:230528", "title": "The effect of cortisol on the excitability of the rat muscle fibre membrane and neuromuscular transmission.", "content": "The present experiments show that cortisol when applied in vitro, exerted two different effects on the electrical excitability of the diaphragm muscle fibre membrane and on the neuromuscular transmission depending on the concentration used. At low concentrations (2.5X10(-6) mol.l-1) it potentiated action potentials, increased resting membrane polarization by 3--4 mV and did not affect neuromuscular transmission. Higher concentrations (10(-2) mol.l-1) suppressed the action potential to a certain extent, depolarized the muscle fibre membrane by 6 mV and reduced the amplitudes of m.e.p.p.s and e.p.p.s as well as those of iontophoretically evoked acetylcholine potentials. It was concluded that the effect of low concentrations of cortisol is primary and is probably due to the enhancement of resting membrane permeability for K+ ions and to the changes in ion channels. Cortisol in high doses increased muscle oxygen consumption, so that its suppressing effect might be due to inhibition of energy metabolism.", "contents": "The effect of cortisol on the excitability of the rat muscle fibre membrane and neuromuscular transmission. The present experiments show that cortisol when applied in vitro, exerted two different effects on the electrical excitability of the diaphragm muscle fibre membrane and on the neuromuscular transmission depending on the concentration used. At low concentrations (2.5X10(-6) mol.l-1) it potentiated action potentials, increased resting membrane polarization by 3--4 mV and did not affect neuromuscular transmission. Higher concentrations (10(-2) mol.l-1) suppressed the action potential to a certain extent, depolarized the muscle fibre membrane by 6 mV and reduced the amplitudes of m.e.p.p.s and e.p.p.s as well as those of iontophoretically evoked acetylcholine potentials. It was concluded that the effect of low concentrations of cortisol is primary and is probably due to the enhancement of resting membrane permeability for K+ ions and to the changes in ion channels. Cortisol in high doses increased muscle oxygen consumption, so that its suppressing effect might be due to inhibition of energy metabolism."}
{"id": "PMID:230537", "title": "The effect of prostaglandin E2 infusion in the fetal lamb on fetal plasma ACTH, prolactin and cortisol concentrations.", "content": "PGE2 (2 micrograms/min) has been infused for 1h into the fetal jugular vein of 8 chronically catheterized fetuses on 13 occasions from 112 to 138 days gestation. Infusion of ethanol vehicle alone was conducted in fetuses from 111-139 days gestation. PGE2 administration produced a significant increase in fetal plasma cortisol after 30 min. No significant change was observed in fetal plasma prolactin concentration. Fetal plasma ACTH concentration was significantly elevated above resting concentration after 30 min. of PGE2 infusion. Metabolic clearance rate of PGE2 was 860 ml/min or 350 ml/kg/min. Intrauterine pressure was not changes during the infusion at any gestational age.", "contents": "The effect of prostaglandin E2 infusion in the fetal lamb on fetal plasma ACTH, prolactin and cortisol concentrations. PGE2 (2 micrograms/min) has been infused for 1h into the fetal jugular vein of 8 chronically catheterized fetuses on 13 occasions from 112 to 138 days gestation. Infusion of ethanol vehicle alone was conducted in fetuses from 111-139 days gestation. PGE2 administration produced a significant increase in fetal plasma cortisol after 30 min. No significant change was observed in fetal plasma prolactin concentration. Fetal plasma ACTH concentration was significantly elevated above resting concentration after 30 min. of PGE2 infusion. Metabolic clearance rate of PGE2 was 860 ml/min or 350 ml/kg/min. Intrauterine pressure was not changes during the infusion at any gestational age."}
{"id": "PMID:230538", "title": "Unsaturated fatty acid effect on cyclic AMP levels in human embryo lung fibroblasts.", "content": "The addition of arachidonic acid at 250 muM to cultures of human embryo lung fibroblasts (IMR-90) increases cellular cyclic AMP levels within 5 minutes to approximately 15-fold over basal. Other unsaturated fatty acids, 11, 14, 17-eicosatrienoic, linoleic, 8, 11, 14-eicosatrienoic and oleic also cause similar rapid elevation of cellular cyclic AMP. During this time interval, no detectable conversion of the added linoleic or arachidonic acids to prostaglandin is observed. These cells produce prostaglandins at measurable concentrations in response to treatment with ascorbic acid or bradykinin. Saturated fatty acids have no influence on cyclic AMP levels in these cells. This effect of unsaturated fatty acids on cellular cyclic AMP levels varies with the cell type. For example, smooth muscle and endothelial cells obtained from the calf pulmonary artery show very little or no increase in cellular cyclic AMP upon exposure to arachidonic acid.", "contents": "Unsaturated fatty acid effect on cyclic AMP levels in human embryo lung fibroblasts. The addition of arachidonic acid at 250 muM to cultures of human embryo lung fibroblasts (IMR-90) increases cellular cyclic AMP levels within 5 minutes to approximately 15-fold over basal. Other unsaturated fatty acids, 11, 14, 17-eicosatrienoic, linoleic, 8, 11, 14-eicosatrienoic and oleic also cause similar rapid elevation of cellular cyclic AMP. During this time interval, no detectable conversion of the added linoleic or arachidonic acids to prostaglandin is observed. These cells produce prostaglandins at measurable concentrations in response to treatment with ascorbic acid or bradykinin. Saturated fatty acids have no influence on cyclic AMP levels in these cells. This effect of unsaturated fatty acids on cellular cyclic AMP levels varies with the cell type. For example, smooth muscle and endothelial cells obtained from the calf pulmonary artery show very little or no increase in cellular cyclic AMP upon exposure to arachidonic acid."}
{"id": "PMID:230539", "title": "PGF2 alpha, thromboxane B2 and HETE levels in gerbil brain cortex after ligation of common carotid arteries and decapitation.", "content": "The effects of ligation of both common carotid arteries in the gerbil on the levels of PGF2 alpha, TXB2, HETE and of energy metabolites in brain cortex, have been investigated. Also, in the same experimental conditions the changes of cyclic AMP in brain cortex, cerebellum, striatum and hippocampus have been monitored. ATP, glycogen, glucose and phosphocreatine decrease whereas, lactate and cyclic AMP are enhanced in the ischemic brain, as previously reported. In contrast, levels of arachidonic acid metabolites are not modified. During ischemia following decapitation, instead, PGF2 alpha, and TXB2, show considerable increase.", "contents": "PGF2 alpha, thromboxane B2 and HETE levels in gerbil brain cortex after ligation of common carotid arteries and decapitation. The effects of ligation of both common carotid arteries in the gerbil on the levels of PGF2 alpha, TXB2, HETE and of energy metabolites in brain cortex, have been investigated. Also, in the same experimental conditions the changes of cyclic AMP in brain cortex, cerebellum, striatum and hippocampus have been monitored. ATP, glycogen, glucose and phosphocreatine decrease whereas, lactate and cyclic AMP are enhanced in the ischemic brain, as previously reported. In contrast, levels of arachidonic acid metabolites are not modified. During ischemia following decapitation, instead, PGF2 alpha, and TXB2, show considerable increase."}
{"id": "PMID:230540", "title": "Failure of prostaglandins E1 and E2 to alter canine gastric mucosal cyclic nucleotides.", "content": "The action of prostaglandins and indomethacin on gastric mucosal cyclic nucleotide concentrations was evaluated in 18 anesthetized mongrel dogs. Prostaglandins E1 (PGE1) and E2 (PGE2) (25 microgram/kg bolus, then 2 micrograms/kg/min) were administered both intravenously (4 experiments; femoral vein) and directly into the gastric mucosal circulation (10 experiments; superior mesenteric artery). The possible synergistic effect of pre-treatment and continuous arterial infusion of indomethacin (5 mg/kg bolus for 5 min, then 5 mg/min), a prostaglandin synthetase inhibitor, with PGE2 was studied in 4 experiments. Antral and fundic mucosa were biopsied and measured by radioimmunoassay for cyclic nucleotides. Doses of PGE1 and PGE2 which inhibited histamine-stimulated canine gastric acid secretion did not significantly alter antral or fundic mucosal cyclic nucleotide concentrations. Concomitant infusion of PGE2 with indomethacin did not potentiate the mucosal nucleotide response compared to PGE2 alone. These studies fail to implicate cyclic nucleotides as mediators of the inhibitory acid response response induced by PGE1 or PGE2 in intact dog stomach.", "contents": "Failure of prostaglandins E1 and E2 to alter canine gastric mucosal cyclic nucleotides. The action of prostaglandins and indomethacin on gastric mucosal cyclic nucleotide concentrations was evaluated in 18 anesthetized mongrel dogs. Prostaglandins E1 (PGE1) and E2 (PGE2) (25 microgram/kg bolus, then 2 micrograms/kg/min) were administered both intravenously (4 experiments; femoral vein) and directly into the gastric mucosal circulation (10 experiments; superior mesenteric artery). The possible synergistic effect of pre-treatment and continuous arterial infusion of indomethacin (5 mg/kg bolus for 5 min, then 5 mg/min), a prostaglandin synthetase inhibitor, with PGE2 was studied in 4 experiments. Antral and fundic mucosa were biopsied and measured by radioimmunoassay for cyclic nucleotides. Doses of PGE1 and PGE2 which inhibited histamine-stimulated canine gastric acid secretion did not significantly alter antral or fundic mucosal cyclic nucleotide concentrations. Concomitant infusion of PGE2 with indomethacin did not potentiate the mucosal nucleotide response compared to PGE2 alone. These studies fail to implicate cyclic nucleotides as mediators of the inhibitory acid response response induced by PGE1 or PGE2 in intact dog stomach."}
{"id": "PMID:230541", "title": "The effects of synthetic prostaglandin analogs on canine hepatic bile flow.", "content": "The synthetic prostaglandin analogs 16, 16-dimethyl PGF2 alpha and 16, 16-dimethyl PGE2 were administered to dogs with chronic biliary and gastric fistulas. The effects of 16, 16 diMePGF2 alpha and 16, 16 diMePGE2 were evaluated on bile flow and composition and bile adenosine 3', 5' monophosphate (cyclic AMP) secretion. 16, 16 diMePGF2 alpha in doses of 0.125 and 0.25 microgram-kg-min significantly increased hepatic bile flow. The choleresis was characterized by increased chloride and bicarbonate secretion. Measurement by radioimmunoassay of bile cyclic AMP concentration demonstrated no evident increase in bile cyclic AMP secretion associated with the choleresis produced by 16, 16 diMePGF2 alpha. The administration of 16, 16 diMePGE2 in a dose range 0.01 to 1.0 microgram-kg-min did not significantly alter bile flow rates or composition. Bile erythritol-14C clearance, a measure of canalicular bile flow, was significantly increased by PGF2 alpha but not by 16, 16-dimethyl PGF2 alpha, suggesting that the mechanism of action of PGF2 alpha in stimulating hepatic bile flow may be different from that involved in 16, 16-dimethyl PGF2 alpha choleresis. The results of this study indicate that the synthetic PGF2 alpha analog produces a choleretic response not mediated by adenylate cyclase and associated with increased chloride and bicarbonate secretion.", "contents": "The effects of synthetic prostaglandin analogs on canine hepatic bile flow. The synthetic prostaglandin analogs 16, 16-dimethyl PGF2 alpha and 16, 16-dimethyl PGE2 were administered to dogs with chronic biliary and gastric fistulas. The effects of 16, 16 diMePGF2 alpha and 16, 16 diMePGE2 were evaluated on bile flow and composition and bile adenosine 3', 5' monophosphate (cyclic AMP) secretion. 16, 16 diMePGF2 alpha in doses of 0.125 and 0.25 microgram-kg-min significantly increased hepatic bile flow. The choleresis was characterized by increased chloride and bicarbonate secretion. Measurement by radioimmunoassay of bile cyclic AMP concentration demonstrated no evident increase in bile cyclic AMP secretion associated with the choleresis produced by 16, 16 diMePGF2 alpha. The administration of 16, 16 diMePGE2 in a dose range 0.01 to 1.0 microgram-kg-min did not significantly alter bile flow rates or composition. Bile erythritol-14C clearance, a measure of canalicular bile flow, was significantly increased by PGF2 alpha but not by 16, 16-dimethyl PGF2 alpha, suggesting that the mechanism of action of PGF2 alpha in stimulating hepatic bile flow may be different from that involved in 16, 16-dimethyl PGF2 alpha choleresis. The results of this study indicate that the synthetic PGF2 alpha analog produces a choleretic response not mediated by adenylate cyclase and associated with increased chloride and bicarbonate secretion."}
{"id": "PMID:230542", "title": "I - Prostaglandin hyperalgesia, a cAMP/Ca2+ dependent process.", "content": "Prostaglandins stimulate cAMP increase in several biological systems including CNS. The possible participation of a cAMP/Ca2+ related mechanism in prostaglandin induced hyperalgesia in the rat paw, as measured by a modification of the Randall-Selitto method was investigated. A serie of agents was administered in the paw in an attempt to change either Ca2+ or cyclic AMP concentration at the nociceptive terminations. PGE2, dibutyryl cyclic AMP, isoprenaline, noradrenaline, adrenaline, Ca2+ionophore (A23187), BaCl2 caused a dose dependent hyperalgesia. The hyperalgesic effect of these substances was enhanced by methyl-xanthines. Cyclic GMP as well as agents which interfere with Ca2+ influx (verapamil and lanthanum) were local analgesics in normal and hyperalgesic paws.", "contents": "I - Prostaglandin hyperalgesia, a cAMP/Ca2+ dependent process. Prostaglandins stimulate cAMP increase in several biological systems including CNS. The possible participation of a cAMP/Ca2+ related mechanism in prostaglandin induced hyperalgesia in the rat paw, as measured by a modification of the Randall-Selitto method was investigated. A serie of agents was administered in the paw in an attempt to change either Ca2+ or cyclic AMP concentration at the nociceptive terminations. PGE2, dibutyryl cyclic AMP, isoprenaline, noradrenaline, adrenaline, Ca2+ionophore (A23187), BaCl2 caused a dose dependent hyperalgesia. The hyperalgesic effect of these substances was enhanced by methyl-xanthines. Cyclic GMP as well as agents which interfere with Ca2+ influx (verapamil and lanthanum) were local analgesics in normal and hyperalgesic paws."}
{"id": "PMID:230543", "title": "II - Prostaglandin hyperalgesia: the peripheral analgesic activity of morphine, enkephalins and opioid antagonists.", "content": "Morphine, enkephalins, nalorphine, naloxone and pentazocine are shown to have a peripheral analgesic effect. In our modification of the Randall-Selitto test these substances were 50--100 times more potent than a standard local anaesthetic, lidocaine. At this peripheral site, naloxone did not antagonize the effect of morphine. Morphine had a marked analgesic effect on the hyperalgesia induced by PGE2 and PGI2, BaCl2, Ca2+ ionophore A23187, isoprenaline but not on that induced by dibutyryl cyclic AMP. It was suggested that the peripheral analgesic effect of morphine is due to an inhibition of adenylate-cyclase activity.", "contents": "II - Prostaglandin hyperalgesia: the peripheral analgesic activity of morphine, enkephalins and opioid antagonists. Morphine, enkephalins, nalorphine, naloxone and pentazocine are shown to have a peripheral analgesic effect. In our modification of the Randall-Selitto test these substances were 50--100 times more potent than a standard local anaesthetic, lidocaine. At this peripheral site, naloxone did not antagonize the effect of morphine. Morphine had a marked analgesic effect on the hyperalgesia induced by PGE2 and PGI2, BaCl2, Ca2+ ionophore A23187, isoprenaline but not on that induced by dibutyryl cyclic AMP. It was suggested that the peripheral analgesic effect of morphine is due to an inhibition of adenylate-cyclase activity."}
{"id": "PMID:230544", "title": "Evidence for separate PGD2 and PGF2 alpha receptors in the canine mesenteric vascular bed.", "content": "Potential interactions between PGD2 and PGF2 alpha in the mesenteric and renal vascular beds were investigated in the anesthetized dog. Regional blood flows were measured with electromagnetic flow probes. PGD2, PGF2 alpha and Norepinephrine (NE) were injected as a bolus directly into the appropriate artery, and responses to these agents were obtained before, during and after infusion of either PGD2 or PGF2 alpha into the left ventricle. In each case, the infused prostaglandin caused vascular effects of its own. Left ventricular infusion of PGD2 reduced responses to local injections of PGD2 in the intestine, and a similar effect was observed for PGF2 alpha, suggesting significant receptor or receptor-like interactions for each of the prostanoids. However, systemic infusion of prostaglandin F2 alpha (20--100 ng/kg/min) had no effect on renal or mesenteric vascular responses to local injection of prostaglandin D2. Similarly, PGD2 administration (100 ng/kg/min) did not affect responses to PGF2 alpha in the intestine. The present results therefore suggest that these prostaglandins, i.e., D2 and F2 alpha, act through separate receptors in the mesenteric and renal vascular beds. In addition, increased prostaglandin F2 alpha levels produced by infusion of F2 alpha reduced mesenteric but not renal blood flow, suggesting that redistribution of cardiac output might participate in side effects often observed with clinical use of this prostaglandin, such as nausea and abdominal pain.", "contents": "Evidence for separate PGD2 and PGF2 alpha receptors in the canine mesenteric vascular bed. Potential interactions between PGD2 and PGF2 alpha in the mesenteric and renal vascular beds were investigated in the anesthetized dog. Regional blood flows were measured with electromagnetic flow probes. PGD2, PGF2 alpha and Norepinephrine (NE) were injected as a bolus directly into the appropriate artery, and responses to these agents were obtained before, during and after infusion of either PGD2 or PGF2 alpha into the left ventricle. In each case, the infused prostaglandin caused vascular effects of its own. Left ventricular infusion of PGD2 reduced responses to local injections of PGD2 in the intestine, and a similar effect was observed for PGF2 alpha, suggesting significant receptor or receptor-like interactions for each of the prostanoids. However, systemic infusion of prostaglandin F2 alpha (20--100 ng/kg/min) had no effect on renal or mesenteric vascular responses to local injection of prostaglandin D2. Similarly, PGD2 administration (100 ng/kg/min) did not affect responses to PGF2 alpha in the intestine. The present results therefore suggest that these prostaglandins, i.e., D2 and F2 alpha, act through separate receptors in the mesenteric and renal vascular beds. In addition, increased prostaglandin F2 alpha levels produced by infusion of F2 alpha reduced mesenteric but not renal blood flow, suggesting that redistribution of cardiac output might participate in side effects often observed with clinical use of this prostaglandin, such as nausea and abdominal pain."}
{"id": "PMID:230545", "title": "Receptor binding in various tissues of PGE2, PGF2 alpha and sulprostone, a novel PGE2-derivative.", "content": "Sulprostone is a tissue-specific PGE2-derivative with high abortifacient activity in various species including man. The dissociation constant KD of the receptor binding of this compound was compared with PGE2 and PGF2 alpha in various tissue preparations of different species. A structure-binding relationship was developed from competition curves after a logit/log transformation. It is demonstrated that the relative affinities of Sulprostone, PGE2 and PGF2 alpha remain essentially constant in all the tissues investigated. It is concluded that the tissue-specificity of Sulprostone cannot be ascribed to structural differences of the receptor molecule.", "contents": "Receptor binding in various tissues of PGE2, PGF2 alpha and sulprostone, a novel PGE2-derivative. Sulprostone is a tissue-specific PGE2-derivative with high abortifacient activity in various species including man. The dissociation constant KD of the receptor binding of this compound was compared with PGE2 and PGF2 alpha in various tissue preparations of different species. A structure-binding relationship was developed from competition curves after a logit/log transformation. It is demonstrated that the relative affinities of Sulprostone, PGE2 and PGF2 alpha remain essentially constant in all the tissues investigated. It is concluded that the tissue-specificity of Sulprostone cannot be ascribed to structural differences of the receptor molecule."}
{"id": "PMID:230552", "title": "(3,4-Dihydroxybenzyl)-2-imidazoline (DHBI): an analogue of dopamine.", "content": "(3,4-Dihydroxybenzyl)-2-imidazoline (DHBI) was prepared and evaluated for dopamine receptor activity by studying its relaxant effects in the rabbit isolated renal and ear arteries and by measuring its ability to enhance dopamine sensitive adenylate cyclase in the rat striatum. DHBI relaxed both the rabbit isolated renal and ear arteries in the presence of phenoxybenzamine (2. 9 X 10(-5)M) and propranolol (3.4 X 10(-7) M) while dopamine and the specific renal dopamine agonist 6,7-dihydroxy-2-aminotetrahydronaphthalene (6,7-ADTN) demonstrated a ratio of specificity for the renal versus the less responsive ear artery. DHBI did not cause a typical increase in adenylate cyclase activity, however DHBI did attenuate the stimulatory a", "contents": "(3,4-Dihydroxybenzyl)-2-imidazoline (DHBI): an analogue of dopamine. (3,4-Dihydroxybenzyl)-2-imidazoline (DHBI) was prepared and evaluated for dopamine receptor activity by studying its relaxant effects in the rabbit isolated renal and ear arteries and by measuring its ability to enhance dopamine sensitive adenylate cyclase in the rat striatum. DHBI relaxed both the rabbit isolated renal and ear arteries in the presence of phenoxybenzamine (2. 9 X 10(-5)M) and propranolol (3.4 X 10(-7) M) while dopamine and the specific renal dopamine agonist 6,7-dihydroxy-2-aminotetrahydronaphthalene (6,7-ADTN) demonstrated a ratio of specificity for the renal versus the less responsive ear artery. DHBI did not cause a typical increase in adenylate cyclase activity, however DHBI did attenuate the stimulatory a"}
{"id": "PMID:230553", "title": "Effect of ascorbic acid on prolyl hydroxylase activity, collagen hydroxylation and collagen synthesis in human synovial cells in culture.", "content": "Synovial cells derived from patients with either rheumatoid arthritis, or simple joint-trauma were grown in tissue culture. The rheumatoid osteoarthritic and non-arthritic synovial cells in cultured all had similar levels of prolyl hydroxylase activity. Following a 3 hour incubation with ascorbate (10(-4)M), prolyl hydroxylase activity was elevated to a similar extent in all synovial cell cultures examined. The activation of prolyl hydroxylase by ascorbate (10(-4)M) was accompanied by increased radioactive hydroxyproline formation and secretion into the media. Increased amounts of collagenase degradable radioactive protein were also secreted into the media, but no changes in total collagen synthesis (media plus cell layer) were observed as a result of ascorbate supplementation using this assay system.", "contents": "Effect of ascorbic acid on prolyl hydroxylase activity, collagen hydroxylation and collagen synthesis in human synovial cells in culture. Synovial cells derived from patients with either rheumatoid arthritis, or simple joint-trauma were grown in tissue culture. The rheumatoid osteoarthritic and non-arthritic synovial cells in cultured all had similar levels of prolyl hydroxylase activity. Following a 3 hour incubation with ascorbate (10(-4)M), prolyl hydroxylase activity was elevated to a similar extent in all synovial cell cultures examined. The activation of prolyl hydroxylase by ascorbate (10(-4)M) was accompanied by increased radioactive hydroxyproline formation and secretion into the media. Increased amounts of collagenase degradable radioactive protein were also secreted into the media, but no changes in total collagen synthesis (media plus cell layer) were observed as a result of ascorbate supplementation using this assay system."}
{"id": "PMID:230554", "title": "Potentiation of ethyl para-nitrophenyl phenyl-phosphonothioate (EPN)-induced inhibition of liver microsomal carboxylesterase by NAD in vitro in rats.", "content": "The higher inhibition of liver microsomal carboxylesterase (CEase) by EPN, as compared to that of acetylcholinesterase (AchE) may be, at least in part, explained by the present findings that NAD potentiated the anti-CEase, but not anti-AchE, action of EPN. This phenomenon was referred to as \"NAD-effect\" in this paper. NAD-effect was not due to the increased formation of oxygen analog of EPN (EPN=O) by NAD addition through liver microsomal cytochrome P-450 catalyzed monoxygenase, because the amounts of EPN=O formed during incubation in the presence and absence of NAD were not significantly changed as shown by gaschromatography-mass spectrometric estimations. In addition, HAD-effect could be observed in the experiments even under carbon monoxide atmosphere. Such NAD-effect was observed only when NAD, EPN and an unidentified component bound to liver microsomal membrane were co-existent in the incubation mixture.", "contents": "Potentiation of ethyl para-nitrophenyl phenyl-phosphonothioate (EPN)-induced inhibition of liver microsomal carboxylesterase by NAD in vitro in rats. The higher inhibition of liver microsomal carboxylesterase (CEase) by EPN, as compared to that of acetylcholinesterase (AchE) may be, at least in part, explained by the present findings that NAD potentiated the anti-CEase, but not anti-AchE, action of EPN. This phenomenon was referred to as \"NAD-effect\" in this paper. NAD-effect was not due to the increased formation of oxygen analog of EPN (EPN=O) by NAD addition through liver microsomal cytochrome P-450 catalyzed monoxygenase, because the amounts of EPN=O formed during incubation in the presence and absence of NAD were not significantly changed as shown by gaschromatography-mass spectrometric estimations. In addition, HAD-effect could be observed in the experiments even under carbon monoxide atmosphere. Such NAD-effect was observed only when NAD, EPN and an unidentified component bound to liver microsomal membrane were co-existent in the incubation mixture."}
{"id": "PMID:230550", "title": "[Sleep polygraphy with recording of intracranial pressure and measure of cerebral blood volume in hydrocephalic infants (author's transl)].", "content": "This study was carried with the intention of explaining the causes of modifications in intracranial pressure (ICP) during paradoxical sleep (PS) in normal and hydrocephalic infants, and establishing relationships between these modifications and cerebral blood volume (CBV). All tests (conventional sleep polygraphy, ICP measured by a transducer on the fontanel, CBV measured by isotopic labelling of red blood cells in vivo) were carried out without use of surgical procedures. During paradoxical sleep there was a sustained wave of increased intracranial pressure lasting from 10 to 20 minutes, as well as phase-type variations lasting no longer than 1 minute. Increased ICP was also observed in the normal subjects. Recordings show that there is well-defined correlation between the sustained wave of high intracranial pressure and an increase in CBV.", "contents": "[Sleep polygraphy with recording of intracranial pressure and measure of cerebral blood volume in hydrocephalic infants (author's transl)]. This study was carried with the intention of explaining the causes of modifications in intracranial pressure (ICP) during paradoxical sleep (PS) in normal and hydrocephalic infants, and establishing relationships between these modifications and cerebral blood volume (CBV). All tests (conventional sleep polygraphy, ICP measured by a transducer on the fontanel, CBV measured by isotopic labelling of red blood cells in vivo) were carried out without use of surgical procedures. During paradoxical sleep there was a sustained wave of increased intracranial pressure lasting from 10 to 20 minutes, as well as phase-type variations lasting no longer than 1 minute. Increased ICP was also observed in the normal subjects. Recordings show that there is well-defined correlation between the sustained wave of high intracranial pressure and an increase in CBV."}
{"id": "PMID:230551", "title": "[Experimental hepatic encephalopathy. Central nervous system excitability in rats following portacaval anastomosis].", "content": "The excitability of reticulo-thalamo-cortical and reticulo-cortical system (RtCS) was studied by electrical stimulation of reticular formation during waking, slow wave sleep and paradoxical sleep during five weeks in control rats and in rats with portocaval shunt. In control rats, no modification of the excitability of RtCS was observed during the experimentation. In rats with portocaval shunt and from the fourteenth post-operative day, the excitability of RtCS was decreased during waking. All along the post-operative period, the excitability of RtCS was increased during slow wave sleep. No modification of the excitability of RtCS was observed postoperatively during paradoxical sleep. These modifications of the excitability of RtCS during waking and slow wave sleep could be related to quantitative variation of the waking-sleep cycle that have been described in rat with portocaval shunt. Their responsability in the disorganization of the waking-sleep states during the experimental hepatic encephalopathy may be hypothetized.", "contents": "[Experimental hepatic encephalopathy. Central nervous system excitability in rats following portacaval anastomosis]. The excitability of reticulo-thalamo-cortical and reticulo-cortical system (RtCS) was studied by electrical stimulation of reticular formation during waking, slow wave sleep and paradoxical sleep during five weeks in control rats and in rats with portocaval shunt. In control rats, no modification of the excitability of RtCS was observed during the experimentation. In rats with portocaval shunt and from the fourteenth post-operative day, the excitability of RtCS was decreased during waking. All along the post-operative period, the excitability of RtCS was increased during slow wave sleep. No modification of the excitability of RtCS was observed postoperatively during paradoxical sleep. These modifications of the excitability of RtCS during waking and slow wave sleep could be related to quantitative variation of the waking-sleep cycle that have been described in rat with portocaval shunt. Their responsability in the disorganization of the waking-sleep states during the experimental hepatic encephalopathy may be hypothetized."}
{"id": "PMID:230555", "title": "Effect of chronic ethanol administration on serum high density lipoprotein cholesterol in rat.", "content": "In rats chronic ethanol administration was found in fasting state not to induce hypertriglyceridemia but moderate hypercholesterolemia through an increased level of high density lipoprotein cholesterol. In the liver, cholesterol contents slightly and triglyceride centents significantly increased. The result suggests that cholesterol accumulation in the liver leads to an increased level of high density lipoprotein cholesterol.", "contents": "Effect of chronic ethanol administration on serum high density lipoprotein cholesterol in rat. In rats chronic ethanol administration was found in fasting state not to induce hypertriglyceridemia but moderate hypercholesterolemia through an increased level of high density lipoprotein cholesterol. In the liver, cholesterol contents slightly and triglyceride centents significantly increased. The result suggests that cholesterol accumulation in the liver leads to an increased level of high density lipoprotein cholesterol."}
{"id": "PMID:230557", "title": "Introduction and multiplication of bovine Babesia in human cells.", "content": "Bovine erythrocytes parasitised with Babesia major were fused with human HeLa cells by means of Sendai virus. B major parasites entered the HeLa cell cytoplasm and in some cases underwent multiplication over a period of three days.", "contents": "Introduction and multiplication of bovine Babesia in human cells. Bovine erythrocytes parasitised with Babesia major were fused with human HeLa cells by means of Sendai virus. B major parasites entered the HeLa cell cytoplasm and in some cases underwent multiplication over a period of three days."}
{"id": "PMID:230558", "title": "Measurement of immunosuppression in chickens caused by infectious bursal disease vaccines using Brucella abortus strain 19.", "content": "The serological response of chicks to Brucella abortus strain 19 was monitored over a period of seven weeks to assess the degree of immunosuppression caused by vaccination at one day of age with two infectious bursal disease vaccines. One of the vacy. This vaccine caused severe immunosuppression judged by the minimal serological response following B abortus inoculation. The test also detected a significant delay caused by the other vaccine in the development of the serological response but the maximum titre was not significantly different from that in chicks which had received no infectious bursal disease vaccine.", "contents": "Measurement of immunosuppression in chickens caused by infectious bursal disease vaccines using Brucella abortus strain 19. The serological response of chicks to Brucella abortus strain 19 was monitored over a period of seven weeks to assess the degree of immunosuppression caused by vaccination at one day of age with two infectious bursal disease vaccines. One of the vacy. This vaccine caused severe immunosuppression judged by the minimal serological response following B abortus inoculation. The test also detected a significant delay caused by the other vaccine in the development of the serological response but the maximum titre was not significantly different from that in chicks which had received no infectious bursal disease vaccine."}
{"id": "PMID:230559", "title": "Distributions of VA/Q in dog lungs obtained with the 50 compartment and the log normal approach.", "content": "From the lung wash-out ratios of six inert gases that were intravenously administered to 26 anaesthetized normal dogs, 120 distributions of ventilation--perfusion ratios (VA/Q) were determined, using two different techniques: the 50 compartment approach developed by Wagner et al. (1974a) and a least squares curve fitting method, comparing observed and calculated inert gas data corresponding to a single log normal distribution. The latter is defined by three parameters, the (geometric) mean VA/Q, the standard deviation of log VA/Q and a shunt fraction. A unimodal log normal fit was almost always obtained, but in 14 cases the 50 compartment approach yielded a bimodal distribution, which gave a better fit to the data in 7 cases. In most other cases the log normal distribution fitted better; the mean VA/Q's were about equal, but the standard deviations obtained from the log normal fit were often much less. It appears that, whereas in the log normal approach distributions of any sharpness can be fitted, the computer technique used in the 50 compartment approach, involving a smoothing algorithm, shortens and broadens any sharp and narrow peak in them. The effect of different smoothing factors in the 50 compartment approach was investigated. The PaO2 predicted from either distribution was about the same and somewhat less than the actual PaO2, so that one model is not superior to the other in describing oxygen transfer in the lung.", "contents": "Distributions of VA/Q in dog lungs obtained with the 50 compartment and the log normal approach. From the lung wash-out ratios of six inert gases that were intravenously administered to 26 anaesthetized normal dogs, 120 distributions of ventilation--perfusion ratios (VA/Q) were determined, using two different techniques: the 50 compartment approach developed by Wagner et al. (1974a) and a least squares curve fitting method, comparing observed and calculated inert gas data corresponding to a single log normal distribution. The latter is defined by three parameters, the (geometric) mean VA/Q, the standard deviation of log VA/Q and a shunt fraction. A unimodal log normal fit was almost always obtained, but in 14 cases the 50 compartment approach yielded a bimodal distribution, which gave a better fit to the data in 7 cases. In most other cases the log normal distribution fitted better; the mean VA/Q's were about equal, but the standard deviations obtained from the log normal fit were often much less. It appears that, whereas in the log normal approach distributions of any sharpness can be fitted, the computer technique used in the 50 compartment approach, involving a smoothing algorithm, shortens and broadens any sharp and narrow peak in them. The effect of different smoothing factors in the 50 compartment approach was investigated. The PaO2 predicted from either distribution was about the same and somewhat less than the actual PaO2, so that one model is not superior to the other in describing oxygen transfer in the lung."}
{"id": "PMID:230560", "title": "Voluntary changes in ventilation distribution in the lateral posture.", "content": "To determine whether voluntary changes in the pattern of inspiratory muscle contraction influence topographical distribution of ventilation in the lateral decubitus posture during tidal breathing, we studied 4 normal subjects who breathed either naturally (N) or preferentially with intercostal and accessory muscles (IC), or with enhanced motion of the diaphragm and abdomen (Ab). We performed N2 as well as 133Xe washouts (after equilibration) which were measured at the mouth while recording regional count rates by external scintillation detectors. Ventilation per unit volume (delta V/Vo) in the nondependent lung regions was 0.55 +/- 0.05 (mean +/- 1 SD) and 0.42 +/- 0.02 of that in the dependent regions during natural and sustained Ab breathing, respectively. In contrast, during IC breathing this ratio was 0.99 +/- 0.17. Although N2 washout curves obtained during IC breathing more closely approached a monoexponential than did those from N and Ab runs, a two compartment analysis of washouts at the mouth did not demonstrate significant differences between breathing patterns. We conclude that in the lateral posture voluntary relaxation of the diaphragm during tidal breathing distributes the gas preferentially to the nondependent lung regions. Conversely, during N and Ab breathing the preferential ventilation of dependent regions is due to contraction of the diaphragm.", "contents": "Voluntary changes in ventilation distribution in the lateral posture. To determine whether voluntary changes in the pattern of inspiratory muscle contraction influence topographical distribution of ventilation in the lateral decubitus posture during tidal breathing, we studied 4 normal subjects who breathed either naturally (N) or preferentially with intercostal and accessory muscles (IC), or with enhanced motion of the diaphragm and abdomen (Ab). We performed N2 as well as 133Xe washouts (after equilibration) which were measured at the mouth while recording regional count rates by external scintillation detectors. Ventilation per unit volume (delta V/Vo) in the nondependent lung regions was 0.55 +/- 0.05 (mean +/- 1 SD) and 0.42 +/- 0.02 of that in the dependent regions during natural and sustained Ab breathing, respectively. In contrast, during IC breathing this ratio was 0.99 +/- 0.17. Although N2 washout curves obtained during IC breathing more closely approached a monoexponential than did those from N and Ab runs, a two compartment analysis of washouts at the mouth did not demonstrate significant differences between breathing patterns. We conclude that in the lateral posture voluntary relaxation of the diaphragm during tidal breathing distributes the gas preferentially to the nondependent lung regions. Conversely, during N and Ab breathing the preferential ventilation of dependent regions is due to contraction of the diaphragm."}
{"id": "PMID:230568", "title": "Effect of SiO2-liberated macrophage factor on protein synthesis in connective tissue in vitro.", "content": "1. To elucidate the role of macrophages in fibrosis the effect of the SiO2-liberated macrophage factor was assessed on protein synthesis in granulation-tissue slices. SiO2 could be replaced by chrysotile asbestos. The active factor is found in the 45/55% sucrose interface of macrophage homogenate. 2. There is no evidence of the involvement of collagenase. 3. The SiO2 effect is not influenced by the addition of yeast RNA to the incubation medium. 4. At a small concentration of polyvinylpyridine-N-oxide (PVNO) protein synthesis in the granulation tissue slices is stimulated, but at higher concentrations PVNO prevented the liberation of the fibrogenic factor from macrophages by SiO2. 5. Phospholipase C and trypsin inhibited the effect of SiO2, which was partially abolished also by heating, and by repeated freezing and thawing. 6. The macrophage RNAse, its inhibitors and fibroblast mRNA are suggested as key factors in the development of fibrosis.", "contents": "Effect of SiO2-liberated macrophage factor on protein synthesis in connective tissue in vitro. 1. To elucidate the role of macrophages in fibrosis the effect of the SiO2-liberated macrophage factor was assessed on protein synthesis in granulation-tissue slices. SiO2 could be replaced by chrysotile asbestos. The active factor is found in the 45/55% sucrose interface of macrophage homogenate. 2. There is no evidence of the involvement of collagenase. 3. The SiO2 effect is not influenced by the addition of yeast RNA to the incubation medium. 4. At a small concentration of polyvinylpyridine-N-oxide (PVNO) protein synthesis in the granulation tissue slices is stimulated, but at higher concentrations PVNO prevented the liberation of the fibrogenic factor from macrophages by SiO2. 5. Phospholipase C and trypsin inhibited the effect of SiO2, which was partially abolished also by heating, and by repeated freezing and thawing. 6. The macrophage RNAse, its inhibitors and fibroblast mRNA are suggested as key factors in the development of fibrosis."}
{"id": "PMID:230569", "title": "Separation of two serum very low density lipoprotein fractions using starch block electrophoresis.", "content": "A quantitative electrophoretic method has been developed in order to differentiate very low density (VLDL) pre-beta lipoproteins from late pre-beta lipoproteins using starch as a supporting medium. It was possible to obtain a bimodal distribution of lipoprotein lipids from VLDL which on agarose gel electrophoresis had a pre-beta band and a late pre-beta band. Optimal conditions were: ammonium carbonate buffer, mu = 0.025, dialysis prior to electrophoresis. Agarose gel electrophoresis demonstrated that the fast and slow components obtained on starch block electrophoresis corresponded to the pre-beta and late pre-beta band respectively. With increasing migration towards the anode the ratio of cholesterol to triglycerides decreased continuously. It is suggested that the fast triglyceride rich component represent newly secreted VLDL species and the slower component mainly postlipolytic particles. The pre-beta band on agarose gel electrophoresis might represent more newly secreted VLDL than the late pre-beta band. However, it cannot be excluded that part of late pre-beta lipoproteins may be secreted de novo.", "contents": "Separation of two serum very low density lipoprotein fractions using starch block electrophoresis. A quantitative electrophoretic method has been developed in order to differentiate very low density (VLDL) pre-beta lipoproteins from late pre-beta lipoproteins using starch as a supporting medium. It was possible to obtain a bimodal distribution of lipoprotein lipids from VLDL which on agarose gel electrophoresis had a pre-beta band and a late pre-beta band. Optimal conditions were: ammonium carbonate buffer, mu = 0.025, dialysis prior to electrophoresis. Agarose gel electrophoresis demonstrated that the fast and slow components obtained on starch block electrophoresis corresponded to the pre-beta and late pre-beta band respectively. With increasing migration towards the anode the ratio of cholesterol to triglycerides decreased continuously. It is suggested that the fast triglyceride rich component represent newly secreted VLDL species and the slower component mainly postlipolytic particles. The pre-beta band on agarose gel electrophoresis might represent more newly secreted VLDL than the late pre-beta band. However, it cannot be excluded that part of late pre-beta lipoproteins may be secreted de novo."}
{"id": "PMID:230570", "title": "Cyclic AMP, renal function and dihydralazine-stimulated renin secretion in hypertensive patients.", "content": "The concentrations of plasma cAMP and plasma renin activity were determined in arterial and renal venous plasma in nineteen patients investigated for renin-mediated hypertension. The cAMP measurements were performed in two different situations (1) under basal conditions and (2) after i.v. dihydralazine administration, a potent renin stimulation procedure. Thirteen patients had a lateralization of the renin secretion in the basal state and the administration of dihydralazine caused a further marked renin-secretion. The cAMP concentration was higher in the renal veins draining renin-positive kidneys than in the contralateral renal veins. No significant change was observed between the arterial cAMP concentration and the cAMP concentration in either of the renal veins during dihydralazine-stimulated renin secretion. There was no correlation between the cAMP extraction and the renin secretion of the individual kidneys, but the cAMP extraction correlated with the extraction ratio of PAH. These results show that cAMP values are mainly influenced by the renal function and are not related to the state of renin secretion. Increased cAMP levels in renovascular patients and urameic patients are therefore mainly due to defective elimination of the nucleotide by the kidneys.", "contents": "Cyclic AMP, renal function and dihydralazine-stimulated renin secretion in hypertensive patients. The concentrations of plasma cAMP and plasma renin activity were determined in arterial and renal venous plasma in nineteen patients investigated for renin-mediated hypertension. The cAMP measurements were performed in two different situations (1) under basal conditions and (2) after i.v. dihydralazine administration, a potent renin stimulation procedure. Thirteen patients had a lateralization of the renin secretion in the basal state and the administration of dihydralazine caused a further marked renin-secretion. The cAMP concentration was higher in the renal veins draining renin-positive kidneys than in the contralateral renal veins. No significant change was observed between the arterial cAMP concentration and the cAMP concentration in either of the renal veins during dihydralazine-stimulated renin secretion. There was no correlation between the cAMP extraction and the renin secretion of the individual kidneys, but the cAMP extraction correlated with the extraction ratio of PAH. These results show that cAMP values are mainly influenced by the renal function and are not related to the state of renin secretion. Increased cAMP levels in renovascular patients and urameic patients are therefore mainly due to defective elimination of the nucleotide by the kidneys."}
{"id": "PMID:230571", "title": "Injury to human endothelial cells in culture induced by low density lipoproteins.", "content": "Low density lipoproteins (LDL) have been shown to injure culture endothelial cells derived from the human umbilical cord. During a 48 h incubation period LDL significantly increased 51Cr release from prelabelled cells and induced marked cellular injury if the ratio between the LDL cholesterol and the infranatant proteins was kept above 0.1-0.12 mmol/g protein. Actually, an injurious effect of a fixed concentration of LDL could be completely prevented by increasing the concentration of infranatant proteins. High density lipoproteins within physiological concentration ranges had no effect when tested in the presence of infranatant proteins. The effects of LDL were not cell specific because normal as well as LDL receptor negative human skin fibroblasts were injured by LDL.", "contents": "Injury to human endothelial cells in culture induced by low density lipoproteins. Low density lipoproteins (LDL) have been shown to injure culture endothelial cells derived from the human umbilical cord. During a 48 h incubation period LDL significantly increased 51Cr release from prelabelled cells and induced marked cellular injury if the ratio between the LDL cholesterol and the infranatant proteins was kept above 0.1-0.12 mmol/g protein. Actually, an injurious effect of a fixed concentration of LDL could be completely prevented by increasing the concentration of infranatant proteins. High density lipoproteins within physiological concentration ranges had no effect when tested in the presence of infranatant proteins. The effects of LDL were not cell specific because normal as well as LDL receptor negative human skin fibroblasts were injured by LDL."}
{"id": "PMID:230572", "title": "Injury to cultured endothelial cells induced by low density lipoproteins: protection by high density lipoproteins.", "content": "Cultured human endothelial cells derived from umbilical cord veins were injured when exposed to low density lipoproteins (LDL). Addition of high density lipoproteins (HDL), together with LDL, inhibited the cellular injury induced by LDL as demonstrated by lowered 51Cr release and prevention of morphological changes. Serum albumin had a similar, but far weaker effect. Preincubation of the cells with HDL did not reduce injury inflicted during a subsequent incubation with LDL, while preincubation with LDL aggravated later damage. The protective effect of HDL could be overcome by increasing the DLD concentration.", "contents": "Injury to cultured endothelial cells induced by low density lipoproteins: protection by high density lipoproteins. Cultured human endothelial cells derived from umbilical cord veins were injured when exposed to low density lipoproteins (LDL). Addition of high density lipoproteins (HDL), together with LDL, inhibited the cellular injury induced by LDL as demonstrated by lowered 51Cr release and prevention of morphological changes. Serum albumin had a similar, but far weaker effect. Preincubation of the cells with HDL did not reduce injury inflicted during a subsequent incubation with LDL, while preincubation with LDL aggravated later damage. The protective effect of HDL could be overcome by increasing the DLD concentration."}
{"id": "PMID:230574", "title": "Diseases of the human breast: selective isolation and exposure of epithelia and their correlative surface features and histopathology.", "content": "Tissues from seventy-one patients were obtained within one-half hour of biopsy, mastectomy, or reduction mammoplasty and processed for scanning electron microscopy (SEM). Epithelial structures were detected by supravital staining with methylene blue and isolated by microdissection. Mammary lobules and ductules required bacterial collagenase digestion to remove the covering stroma for optimal visualization. Major histopathological categories were compared and correlated with the characteristics observed with methylene blue supravital staining and light microscopy and/or transmission electron microscopy as a function of surface features revealed by SEM. Mammary ducts can be readily distinguished from ductules and lobules by their characteristic surface epithelium. Duct epithelium undergoes a variety of changes in fibrocystic disease (FCD) and in carcinoma. Both apocrine and merocrine secretory activity was observed in the surface epithelium. Proliferation of both epithelial and stromal elements was observed in benign fibroadenomata. Intraductal carcinomas were distinguished by their relative lack of surface microvilli. SEM offers a practical tool in the potential identification of premalignant cells of the human breast epithelium.", "contents": "Diseases of the human breast: selective isolation and exposure of epithelia and their correlative surface features and histopathology. Tissues from seventy-one patients were obtained within one-half hour of biopsy, mastectomy, or reduction mammoplasty and processed for scanning electron microscopy (SEM). Epithelial structures were detected by supravital staining with methylene blue and isolated by microdissection. Mammary lobules and ductules required bacterial collagenase digestion to remove the covering stroma for optimal visualization. Major histopathological categories were compared and correlated with the characteristics observed with methylene blue supravital staining and light microscopy and/or transmission electron microscopy as a function of surface features revealed by SEM. Mammary ducts can be readily distinguished from ductules and lobules by their characteristic surface epithelium. Duct epithelium undergoes a variety of changes in fibrocystic disease (FCD) and in carcinoma. Both apocrine and merocrine secretory activity was observed in the surface epithelium. Proliferation of both epithelial and stromal elements was observed in benign fibroadenomata. Intraductal carcinomas were distinguished by their relative lack of surface microvilli. SEM offers a practical tool in the potential identification of premalignant cells of the human breast epithelium."}
{"id": "PMID:230576", "title": "Prospective on cell surface labeling using the hapten-sandwich method: an integrated approach.", "content": "Specific molecular units on the surface membranes of cells were tagged with markers visible in fluorescence, transmission and scanning electron microscopy. The Hapten-sandwich method does this by the sequential application of hapten-modified anti-cell-surface antibody, anti-hapten antibody and a hapten-modified marker. Details are given for the preparation and testing of the various reagents used in this method. The specificity and efficiency of Hapten-sandwich coupling of hemocyanin to mammary tumor virus (MTV) budding from breast tumor cells was demonstrated by quantitative transmission electron microscopy. Con A and anti-saccharide antibodies were used to demonstrate the presence of various sugars on the surfaces of the mammary tumor cells using fluorescence, transmission and scannings electron microscopy. Some samples were doubly labeled for the simultaneous presence of two different sugars. Light and electron microscopy were used to show that several hormones (insulin(I), hydrocortisone(F), and prolactin) greatly affect the expression of tumor virus and the kind and density of cell surface sugars on mammary tumor cells. Individual cells produced virus and expressed surface sugars independently. A micro-scanning densitometer was used to quantitate the results from fluorescence microscopy. Future advances in cell labeling including other applications of the Hapten-sandwich method, and problems such as the quantitation of electron microscopy labeling are discussed.", "contents": "Prospective on cell surface labeling using the hapten-sandwich method: an integrated approach. Specific molecular units on the surface membranes of cells were tagged with markers visible in fluorescence, transmission and scanning electron microscopy. The Hapten-sandwich method does this by the sequential application of hapten-modified anti-cell-surface antibody, anti-hapten antibody and a hapten-modified marker. Details are given for the preparation and testing of the various reagents used in this method. The specificity and efficiency of Hapten-sandwich coupling of hemocyanin to mammary tumor virus (MTV) budding from breast tumor cells was demonstrated by quantitative transmission electron microscopy. Con A and anti-saccharide antibodies were used to demonstrate the presence of various sugars on the surfaces of the mammary tumor cells using fluorescence, transmission and scannings electron microscopy. Some samples were doubly labeled for the simultaneous presence of two different sugars. Light and electron microscopy were used to show that several hormones (insulin(I), hydrocortisone(F), and prolactin) greatly affect the expression of tumor virus and the kind and density of cell surface sugars on mammary tumor cells. Individual cells produced virus and expressed surface sugars independently. A micro-scanning densitometer was used to quantitate the results from fluorescence microscopy. Future advances in cell labeling including other applications of the Hapten-sandwich method, and problems such as the quantitation of electron microscopy labeling are discussed."}
{"id": "PMID:230579", "title": "Electron probe studies of Na+ - K+-ATPase.", "content": "Use of appropriate reaction conditions allows direct quantitative measurements of the activity of Na-K-ATPase to be made with the electron probe microanalyzer. In addition, the demonstration by microanalysis of the linearity of the complete cytochemical reaction sequence is the first detailed analysis of the elemental sequence in a histochemical method and provides the basis for a visual semi-quantitative analysis of enzyme activity in tissue sections. This technique indicates the potential of electron probe microanalysis as a basic tool in enzymology.", "contents": "Electron probe studies of Na+ - K+-ATPase. Use of appropriate reaction conditions allows direct quantitative measurements of the activity of Na-K-ATPase to be made with the electron probe microanalyzer. In addition, the demonstration by microanalysis of the linearity of the complete cytochemical reaction sequence is the first detailed analysis of the elemental sequence in a histochemical method and provides the basis for a visual semi-quantitative analysis of enzyme activity in tissue sections. This technique indicates the potential of electron probe microanalysis as a basic tool in enzymology."}
{"id": "PMID:230581", "title": "Establishment of anti-TNP antibody-producing human lymphoid lines by preselection for hapten binding followed by EBV transformation.", "content": "Human lymphoblastoid cell lines that produce specific antibody against the hapten trinitrophenyl (TNP) have been established by selecting TNP-binding human B lymphocytes by TNP-rosetting and Ficoll-Isopaque separation, followed by Epstein-Barr virus (EBV) immortalization. Derived lines secreted polyclonal anti-TNP antibodies and contained relatively small numbers of specific rosette- and plaque-forming cells against TNP-RBC. Following rerosetting with TNP-RBC, the frequency of rosette-forming cells increased from 2% to 75%. In parallel, the frequency of plaque-forming cells increased from 0.4% to 30%. The antibody titres in the supernatants increased from 64 to 512 and from 48 to 192, as measured by TNP agglutination and haemolytic assays, respectively. The antibodies were 19S, IgM. The specificity of the anti-TNP antibody was confirmed by the hapten inhibition test, in comparison and cross-reactivity tests with the supernatant of the previously established, EBV-transformed anti-4-hydroxy-3,5-dinitrophenacetic acid (NNP) antibody-producing cell line. Both antibodies were specific: the homologous hapten inhibited them but the heterologous hapten did not.", "contents": "Establishment of anti-TNP antibody-producing human lymphoid lines by preselection for hapten binding followed by EBV transformation. Human lymphoblastoid cell lines that produce specific antibody against the hapten trinitrophenyl (TNP) have been established by selecting TNP-binding human B lymphocytes by TNP-rosetting and Ficoll-Isopaque separation, followed by Epstein-Barr virus (EBV) immortalization. Derived lines secreted polyclonal anti-TNP antibodies and contained relatively small numbers of specific rosette- and plaque-forming cells against TNP-RBC. Following rerosetting with TNP-RBC, the frequency of rosette-forming cells increased from 2% to 75%. In parallel, the frequency of plaque-forming cells increased from 0.4% to 30%. The antibody titres in the supernatants increased from 64 to 512 and from 48 to 192, as measured by TNP agglutination and haemolytic assays, respectively. The antibodies were 19S, IgM. The specificity of the anti-TNP antibody was confirmed by the hapten inhibition test, in comparison and cross-reactivity tests with the supernatant of the previously established, EBV-transformed anti-4-hydroxy-3,5-dinitrophenacetic acid (NNP) antibody-producing cell line. Both antibodies were specific: the homologous hapten inhibited them but the heterologous hapten did not."}
{"id": "PMID:230582", "title": "Rat memory T lymphocytes. II. Differences in macrophage-dependent activation shown by Actinomyces viscosus antigens and by mitogens, using silica in vitro.", "content": "Protein-coated silica, a macrophage toxin, was used to assess the requirement for accessory cells in the induction of an in vitro proliferative response to (i) antigens from Actinomyces viscosus and (ii) the mitogens conconavalin A (Con A) and phytohaemagglutinin (PHA). T cells were obtained from RIC-Sprague-Dawley rats primed in vivo with A. viscosus Nyl by splenectomy and filtering the spleen cell suspensions through Degalan Ig-anti-IgG columns. In the presence of 100 microgram silica/ml during 4 days of culture, the proliferative response of T lymphocytes was not diminished. In contrast, when the T cells were precultured with silica for 24 h, washed, and subsequently cultured with the antigen fractions, antigen-induced proliferation was abolished. This procedure, however, had no influence on mitogen-induced proliferation was abolished. This procedure, however, had no influence on mitogen-induced T-cell activation. It is therefore concluded that the antigen-dependent anamnestic in vitro response (but not activation by mitogens) of rat T lymphocytes needs help from silica-sensitive macrophages.", "contents": "Rat memory T lymphocytes. II. Differences in macrophage-dependent activation shown by Actinomyces viscosus antigens and by mitogens, using silica in vitro. Protein-coated silica, a macrophage toxin, was used to assess the requirement for accessory cells in the induction of an in vitro proliferative response to (i) antigens from Actinomyces viscosus and (ii) the mitogens conconavalin A (Con A) and phytohaemagglutinin (PHA). T cells were obtained from RIC-Sprague-Dawley rats primed in vivo with A. viscosus Nyl by splenectomy and filtering the spleen cell suspensions through Degalan Ig-anti-IgG columns. In the presence of 100 microgram silica/ml during 4 days of culture, the proliferative response of T lymphocytes was not diminished. In contrast, when the T cells were precultured with silica for 24 h, washed, and subsequently cultured with the antigen fractions, antigen-induced proliferation was abolished. This procedure, however, had no influence on mitogen-induced proliferation was abolished. This procedure, however, had no influence on mitogen-induced T-cell activation. It is therefore concluded that the antigen-dependent anamnestic in vitro response (but not activation by mitogens) of rat T lymphocytes needs help from silica-sensitive macrophages."}
{"id": "PMID:230583", "title": "[Effect of menopausal syndromes on symptoms of denture intolerance].", "content": "19 female patients suffering from incompatibility to their dentures with a suspected lack of estrogen were examined gynecologically, endocrinologically and cytologically. Substitution with conjugated estrogen caused in 14 patients improvement of general condition, in 12 persons reduction of symptoms in the oral cavity. Endocrinologically and cytologically no clear differences before and after treatment could be observed.", "contents": "[Effect of menopausal syndromes on symptoms of denture intolerance]. 19 female patients suffering from incompatibility to their dentures with a suspected lack of estrogen were examined gynecologically, endocrinologically and cytologically. Substitution with conjugated estrogen caused in 14 patients improvement of general condition, in 12 persons reduction of symptoms in the oral cavity. Endocrinologically and cytologically no clear differences before and after treatment could be observed."}
{"id": "PMID:230585", "title": "[Clinical aspect and actual frequency of bilateral squamous cell bronchial carcinoma with simultaneous revelation (author's transl)].", "content": "Clinical and physiopathological data about 10 cases of bilateral squamous cell bronchial carcinoma with simultaneous revelation, are reviewed. This clinical form is not rare, usually found by a systematic bilateral endoscopy. In these 10 cases, the clinical and radiological data did not allow to predict the diagnosis before the endoscopy. Physio-pathological mechanisms are not well established. Various hypotheses are propounded : air-way, blood or lymphatic metastases, simultaneous tumoral blossoming, superficial propagation, genetic factors intervention. For these 10 cases, the authors develop arguments for one or another of these mechanisms.", "contents": "[Clinical aspect and actual frequency of bilateral squamous cell bronchial carcinoma with simultaneous revelation (author's transl)]. Clinical and physiopathological data about 10 cases of bilateral squamous cell bronchial carcinoma with simultaneous revelation, are reviewed. This clinical form is not rare, usually found by a systematic bilateral endoscopy. In these 10 cases, the clinical and radiological data did not allow to predict the diagnosis before the endoscopy. Physio-pathological mechanisms are not well established. Various hypotheses are propounded : air-way, blood or lymphatic metastases, simultaneous tumoral blossoming, superficial propagation, genetic factors intervention. For these 10 cases, the authors develop arguments for one or another of these mechanisms."}
{"id": "PMID:230586", "title": "[Unusual tumours of the digestive tract (author's transl)].", "content": "The authors summarize the difficulties in diagnosis some tumour-like lesions or digestive tumours. They rely upon thirty years experience in digestive pathology and upon a survey of relevant literature. They recall the difficulties arising from the inflammatory tumour-like lesions (infiltrating sclerosis or granulomas, colitis cystica profunda, inflammatory polyps). They mention the circumstances which bring about errors or incomplete diagnosis among these very tumours. Some difficulties are due to the circumstances in which these tumours appear : the digestive cancers of the child, the assocations of some family cancers (the ill-forming tumours and the dysembryoplasic cancers, and lastly the connections that exist between some inflammatory or dystrophic diseases and tumours. Other difficulties depend upon the topography or the tumorous structure. Paneth-cell carcinomas, goblet cell carcinoid are chosen as instances among epithelial tumours. In the group of non-epithelial tumours, digestive localizations of angiomatosis and of lymphomatosis may cause errors. Likewise this can be applied to some secondary digestive tumours. Regarding these difficulties, the authors stress the necessity of a close cooperation between gastro-enterologists, surgeons and pathologists. They also stress the strict observance of techniques in fixation and preparation of specimens and biopsies, and also the necessity of completing, if need be, the habitual microscopy through more elaborate explorations (histochemistry, electron microscopy...).", "contents": "[Unusual tumours of the digestive tract (author's transl)]. The authors summarize the difficulties in diagnosis some tumour-like lesions or digestive tumours. They rely upon thirty years experience in digestive pathology and upon a survey of relevant literature. They recall the difficulties arising from the inflammatory tumour-like lesions (infiltrating sclerosis or granulomas, colitis cystica profunda, inflammatory polyps). They mention the circumstances which bring about errors or incomplete diagnosis among these very tumours. Some difficulties are due to the circumstances in which these tumours appear : the digestive cancers of the child, the assocations of some family cancers (the ill-forming tumours and the dysembryoplasic cancers, and lastly the connections that exist between some inflammatory or dystrophic diseases and tumours. Other difficulties depend upon the topography or the tumorous structure. Paneth-cell carcinomas, goblet cell carcinoid are chosen as instances among epithelial tumours. In the group of non-epithelial tumours, digestive localizations of angiomatosis and of lymphomatosis may cause errors. Likewise this can be applied to some secondary digestive tumours. Regarding these difficulties, the authors stress the necessity of a close cooperation between gastro-enterologists, surgeons and pathologists. They also stress the strict observance of techniques in fixation and preparation of specimens and biopsies, and also the necessity of completing, if need be, the habitual microscopy through more elaborate explorations (histochemistry, electron microscopy...)."}
{"id": "PMID:230587", "title": "[Transient osteoporosis of the hip in pregnancy. Report of three cases (author's transl)].", "content": "Three cases of transient osteoporosis of the hip in pregnant women are reported, and compared with 13 similar observations, published in world literature. The disease occurs during second half of pregnancy, revealed byrnotion hip pain, and slight limitation of mobility. On radiography, the femoral head and acetabulum are radiolucent and heterogenous. These modifications may be impressive but careful analysis of X rays rules out coxitis or malignant osteolysis. Major functional disturbance is common but the course of pregnancy and delivery is not impaired. Healing, without sequelae, occurs in a few months. Before delivery, attention should be paid to the fetal risk when prescribing X rays examinations or drug treatment. Pathogeny is unclear; the role of nerve or vein compression by the pregnant womb is discussed.", "contents": "[Transient osteoporosis of the hip in pregnancy. Report of three cases (author's transl)]. Three cases of transient osteoporosis of the hip in pregnant women are reported, and compared with 13 similar observations, published in world literature. The disease occurs during second half of pregnancy, revealed byrnotion hip pain, and slight limitation of mobility. On radiography, the femoral head and acetabulum are radiolucent and heterogenous. These modifications may be impressive but careful analysis of X rays rules out coxitis or malignant osteolysis. Major functional disturbance is common but the course of pregnancy and delivery is not impaired. Healing, without sequelae, occurs in a few months. Before delivery, attention should be paid to the fetal risk when prescribing X rays examinations or drug treatment. Pathogeny is unclear; the role of nerve or vein compression by the pregnant womb is discussed."}
{"id": "PMID:230588", "title": "[Severe forms of imported malaria concerning three pernicious attacks and a black water fever (hemoglobinuria) (author's transl)].", "content": "Four severe cases of imported malaria are reported here. Three of them are pernicious and the fourth is a black water fever (hemoglobinuria). The difficulties of initial diagnosis are exposed. There was no mortality in these four cases which represent the annual recruiting of a multipurpose intensive care unit. But the complications are severe in contradiction with easy effective chemoprophylaxis. The principles of treatment and prophylaxis are resumed in the light of these four observations.", "contents": "[Severe forms of imported malaria concerning three pernicious attacks and a black water fever (hemoglobinuria) (author's transl)]. Four severe cases of imported malaria are reported here. Three of them are pernicious and the fourth is a black water fever (hemoglobinuria). The difficulties of initial diagnosis are exposed. There was no mortality in these four cases which represent the annual recruiting of a multipurpose intensive care unit. But the complications are severe in contradiction with easy effective chemoprophylaxis. The principles of treatment and prophylaxis are resumed in the light of these four observations."}
{"id": "PMID:230589", "title": "[Gammacisternography and fronto-basal head injuries (author's transl)].", "content": "The authors give the results of 65 radioisotopic cisternographies for suspected rhinorrheas in frontal basal head injuries. Indium 111-DTPA lombar injection allows the investigation at least for 48 hours. After localisating the CSF fistulae, the gammacisternography permits us to study associated CSF circulation anomalies. Results and discussion give the correlation between positive tests and surgical findings. The best successful conditions of exploration are enough activity and a fluent clinical leakage of CSF. Nasal coton pledgets improve the success of the exploration.", "contents": "[Gammacisternography and fronto-basal head injuries (author's transl)]. The authors give the results of 65 radioisotopic cisternographies for suspected rhinorrheas in frontal basal head injuries. Indium 111-DTPA lombar injection allows the investigation at least for 48 hours. After localisating the CSF fistulae, the gammacisternography permits us to study associated CSF circulation anomalies. Results and discussion give the correlation between positive tests and surgical findings. The best successful conditions of exploration are enough activity and a fluent clinical leakage of CSF. Nasal coton pledgets improve the success of the exploration."}
{"id": "PMID:230590", "title": "[Clinical and bacteriological evaluation of sisomicin in sixteen cases of severe bronchopulmonary infection (author's transl)].", "content": "Sisomicin, an aminoglycoside antibiotic, was used as sole bactericidal therapy in sixteen cases of severe bronchopulmonary infection for an average of 11,5 days (range 7 to 14) with a dose of 3,5 mg/kg per day in three intramuscular injections. Fifteen of these hospitalized patients presented with chronic airway obstruction which resulted in lowered O2 saturation (SaO2 congruent to 86,1%, range 74 to 93) and, in twelve patients, hypercapnia (PaCO2 = 55,7 torr, range 33--73). Two of these patients were under continuous assisted ventilation. Two patients had a lower lobe infiltrate and a lung abscess respectively. Proteus (n = 3), Pseudomonas (n = 9), K. pneumoniae (n = 2), E. Coli (n = 1), Enterobacter (n = 1), S. aureus (n = 1) and D. pneumoniae (n = 1) were the dominant organisms in the bronchial secretions isolated by Mulder's method; P. aeruginosa was associated with K. pneumoniae, P. rettgeri and E. coli respectively in three cases. In thirteen cases, either a clinical cure (n = 2) or a definite improvement was observed (sputum volume and purulence, auscultatory signs, temperature). However, among these patients were three cases of superinfection/colonization and two cases of persistent organisms. In addition, in two of the three cases showing no improvement colonization occured. The favorable results of this study appear to be due to vigorous antibiotic therapy combined with intensive adjunct therapy. No adverse local or systemic reactions clearly attributable to the drug were observed.", "contents": "[Clinical and bacteriological evaluation of sisomicin in sixteen cases of severe bronchopulmonary infection (author's transl)]. Sisomicin, an aminoglycoside antibiotic, was used as sole bactericidal therapy in sixteen cases of severe bronchopulmonary infection for an average of 11,5 days (range 7 to 14) with a dose of 3,5 mg/kg per day in three intramuscular injections. Fifteen of these hospitalized patients presented with chronic airway obstruction which resulted in lowered O2 saturation (SaO2 congruent to 86,1%, range 74 to 93) and, in twelve patients, hypercapnia (PaCO2 = 55,7 torr, range 33--73). Two of these patients were under continuous assisted ventilation. Two patients had a lower lobe infiltrate and a lung abscess respectively. Proteus (n = 3), Pseudomonas (n = 9), K. pneumoniae (n = 2), E. Coli (n = 1), Enterobacter (n = 1), S. aureus (n = 1) and D. pneumoniae (n = 1) were the dominant organisms in the bronchial secretions isolated by Mulder's method; P. aeruginosa was associated with K. pneumoniae, P. rettgeri and E. coli respectively in three cases. In thirteen cases, either a clinical cure (n = 2) or a definite improvement was observed (sputum volume and purulence, auscultatory signs, temperature). However, among these patients were three cases of superinfection/colonization and two cases of persistent organisms. In addition, in two of the three cases showing no improvement colonization occured. The favorable results of this study appear to be due to vigorous antibiotic therapy combined with intensive adjunct therapy. No adverse local or systemic reactions clearly attributable to the drug were observed."}
{"id": "PMID:230591", "title": "[Congenital coronary artery malformations and associated clinical syndromes (author's transl)].", "content": "In 34 cases, corresponding to 3,7% of all patients underwent coronary arteriography for evaluation of anginal syndrome in our laboratory, it was observed a congenital coronary anomaly on their angiograms. The purpose of this paper is to verify the frequency of coronary anomalies and to evaluate relations existing between these anomalies and anginal syndrome. Coronary arteriograms, in 22 cases (2,44%), revealed exclusively; the presence of a coronary anomaly without occlusive coronary disease, which might per se justify angina. They were distributed as follows : 5 with coronary fistula, 2 with coronary aneurysms, 2 cases with single ostium and finally, 13 subjects with hypoplasia of one of the three major coronary arteries. One infant, 14 months old, had a hyperplasic left discending artery (LDA) draining in right ventricle cavity. Her ECG revealed signs of right ventricle overload. All the other cases had a typical angina syndrome with positive stress test. Left cineventriculography demonstrated left ventricle asynergy in 16 patients. We concluded that typical angina syndrome in our 22 patients, may be attributable to coronary anomalies observed at their coronary arteriograms.", "contents": "[Congenital coronary artery malformations and associated clinical syndromes (author's transl)]. In 34 cases, corresponding to 3,7% of all patients underwent coronary arteriography for evaluation of anginal syndrome in our laboratory, it was observed a congenital coronary anomaly on their angiograms. The purpose of this paper is to verify the frequency of coronary anomalies and to evaluate relations existing between these anomalies and anginal syndrome. Coronary arteriograms, in 22 cases (2,44%), revealed exclusively; the presence of a coronary anomaly without occlusive coronary disease, which might per se justify angina. They were distributed as follows : 5 with coronary fistula, 2 with coronary aneurysms, 2 cases with single ostium and finally, 13 subjects with hypoplasia of one of the three major coronary arteries. One infant, 14 months old, had a hyperplasic left discending artery (LDA) draining in right ventricle cavity. Her ECG revealed signs of right ventricle overload. All the other cases had a typical angina syndrome with positive stress test. Left cineventriculography demonstrated left ventricle asynergy in 16 patients. We concluded that typical angina syndrome in our 22 patients, may be attributable to coronary anomalies observed at their coronary arteriograms."}
{"id": "PMID:230592", "title": "[Chronic neurogenic hypernatremia with arhinencephaly (author's transl)].", "content": "A case of chronic neurogenic hypernatremia with arhinencephaly has been studied. The clinical and biological picture of neurogenic hypernatremia is reviewed. Hormonal studies have been performed, to try to clear up the physiopathology of this syndrom.", "contents": "[Chronic neurogenic hypernatremia with arhinencephaly (author's transl)]. A case of chronic neurogenic hypernatremia with arhinencephaly has been studied. The clinical and biological picture of neurogenic hypernatremia is reviewed. Hormonal studies have been performed, to try to clear up the physiopathology of this syndrom."}
{"id": "PMID:230593", "title": "[Colonic Crohn's disease and oral contraceptive (author's transl)].", "content": "One colonic Crohn's disease case is reported in a young woman under pill. Stopping it, recovery was observed. Oral contraceptive responsability is pointed out.", "contents": "[Colonic Crohn's disease and oral contraceptive (author's transl)]. One colonic Crohn's disease case is reported in a young woman under pill. Stopping it, recovery was observed. Oral contraceptive responsability is pointed out."}
{"id": "PMID:230594", "title": "[Muscular metastases. A case report (author's transl)].", "content": "Muscular metastases are exceptionally reported. The authors present a case of crural neuralgia in relation with a localisation in the psoas iliacus of a gastric carcinoma. A review of literature defines the rarity of this facts (156 cases) the etiology (carcinome more often) and the explication who is still obscur.", "contents": "[Muscular metastases. A case report (author's transl)]. Muscular metastases are exceptionally reported. The authors present a case of crural neuralgia in relation with a localisation in the psoas iliacus of a gastric carcinoma. A review of literature defines the rarity of this facts (156 cases) the etiology (carcinome more often) and the explication who is still obscur."}
{"id": "PMID:230595", "title": "[Double spontaneous viscero-renal fistula. A report of one case (author's transl)].", "content": "The authors report one case of double spontaneous viscerorenal fistula on the right kidney. After consultation of the world literature, they expose the main character of this lesion. They insist on the transparietal pyelography in the diagnosis and on the surgical treatment.", "contents": "[Double spontaneous viscero-renal fistula. A report of one case (author's transl)]. The authors report one case of double spontaneous viscerorenal fistula on the right kidney. After consultation of the world literature, they expose the main character of this lesion. They insist on the transparietal pyelography in the diagnosis and on the surgical treatment."}
{"id": "PMID:230596", "title": "[Anterior perinephritic phlegmon (author's transl)].", "content": "A case is reported of an unsuspected anterior perinephritic phlegmon which had caused peritonitis of pyelonephritic origin thought to be due to a cholecystitis. The lesion was discovered during laparotomy and intravenous urography at operation demonstrated the condition of the underlying kidney and determined the therapeutic approach and the prognosis.", "contents": "[Anterior perinephritic phlegmon (author's transl)]. A case is reported of an unsuspected anterior perinephritic phlegmon which had caused peritonitis of pyelonephritic origin thought to be due to a cholecystitis. The lesion was discovered during laparotomy and intravenous urography at operation demonstrated the condition of the underlying kidney and determined the therapeutic approach and the prognosis."}
{"id": "PMID:230597", "title": "[Use of a titrated extract of Centella asiatica in chronic hepatic disorders (author's transl)].", "content": "The authors report their preliminary results of a study of the possible therapeutic activity of a titrated extract of Centella asiatica in chronic hepatic disorders. Early results are encouraging, especially from a histological point of view, where improvement in the criteria evaluated was noted in 5 of the 12 patients treated for the longest time. These results have to be assessed in a critical manner until confirmation is obtained by complementary studies.", "contents": "[Use of a titrated extract of Centella asiatica in chronic hepatic disorders (author's transl)]. The authors report their preliminary results of a study of the possible therapeutic activity of a titrated extract of Centella asiatica in chronic hepatic disorders. Early results are encouraging, especially from a histological point of view, where improvement in the criteria evaluated was noted in 5 of the 12 patients treated for the longest time. These results have to be assessed in a critical manner until confirmation is obtained by complementary studies."}
{"id": "PMID:230598", "title": "[About the different steps leading to the quality of medical information (importance of medical computing) (author's transl)].", "content": "To draw the best conclusions from a set of medical data, one must first choose correct, valid, representative and well-expressed information. So it's not sufficient to collect data, but we have to valid them before including them in the records. After having put out the general characteristics of any validation and defined the fields where they can be applied we recommend a method over three steps. First, the physician alone, then the physician with an informatician and again the physician seem concerned by the steps of control. It is particularly important to develop the validation of chronology and generally speaking of evolutive data. Of course, the costs of validation with respect to the large groups of data must be taken into account.", "contents": "[About the different steps leading to the quality of medical information (importance of medical computing) (author's transl)]. To draw the best conclusions from a set of medical data, one must first choose correct, valid, representative and well-expressed information. So it's not sufficient to collect data, but we have to valid them before including them in the records. After having put out the general characteristics of any validation and defined the fields where they can be applied we recommend a method over three steps. First, the physician alone, then the physician with an informatician and again the physician seem concerned by the steps of control. It is particularly important to develop the validation of chronology and generally speaking of evolutive data. Of course, the costs of validation with respect to the large groups of data must be taken into account."}
{"id": "PMID:230599", "title": "[Headaches and cervicarthrosis : arthrosis, vascular or psychic origin? (author's transl)].", "content": "Cervicarthrosis is an extremely frequent disease yet often appears as asymptomatic. It can however give birth to varied clinical manifestations, for which it can be held responsible together with other factors : inflammatory as in cervico-brachial neuralgia, vascular as in cervicarthrosis medullopathy, psychological as in posterior cervicalgia and headaches belonging to the classical Barr\u00e9-Li\u00e9ou syndrom. We must stress the therapeutic interest of tiapride, which acts on the algic element as well as on the element of psychological tension in the last case.", "contents": "[Headaches and cervicarthrosis : arthrosis, vascular or psychic origin? (author's transl)]. Cervicarthrosis is an extremely frequent disease yet often appears as asymptomatic. It can however give birth to varied clinical manifestations, for which it can be held responsible together with other factors : inflammatory as in cervico-brachial neuralgia, vascular as in cervicarthrosis medullopathy, psychological as in posterior cervicalgia and headaches belonging to the classical Barr\u00e9-Li\u00e9ou syndrom. We must stress the therapeutic interest of tiapride, which acts on the algic element as well as on the element of psychological tension in the last case."}
{"id": "PMID:230603", "title": "Objective evaluation and prediction of client improvement in mental health aftercare.", "content": "External funding sources and review boards appropriately are mandating more objective, clear-cut demonstrations of mental health program effectiveness. Mental health adult aftercare programs, traditionally characterized by globally-defined, imprecise goal and outcome measurement, can be objectively, empirically evaluated. The current paper illustrates how structured ratings and observations can be used feasibly to yield quantified \"hard data\" on client improvement and program effectiveness. The paper also presents the results of a program evaluation research study which indicate that while psychosocial history variables predict initial client appearance in aftercare, program participation-involvement behavior (and not psychosocial history) predict client improvement. Implications of these finds and the need for objective approaches to aftercare program evaluation are discussed.", "contents": "Objective evaluation and prediction of client improvement in mental health aftercare. External funding sources and review boards appropriately are mandating more objective, clear-cut demonstrations of mental health program effectiveness. Mental health adult aftercare programs, traditionally characterized by globally-defined, imprecise goal and outcome measurement, can be objectively, empirically evaluated. The current paper illustrates how structured ratings and observations can be used feasibly to yield quantified \"hard data\" on client improvement and program effectiveness. The paper also presents the results of a program evaluation research study which indicate that while psychosocial history variables predict initial client appearance in aftercare, program participation-involvement behavior (and not psychosocial history) predict client improvement. Implications of these finds and the need for objective approaches to aftercare program evaluation are discussed."}
{"id": "PMID:230604", "title": "Family care for the mentally ill: a new perspective.", "content": "Family care has been a subject of controversy since large numbers of discharged psychiatric patients have been placed in these homes. The debate has centered on whether such community facilities offer a meaningful alternative in caring for the mentally ill. Findings of a study dealing with the quality of care in the homes and factors deemed responsible for these conditions provide a new perspective on the dilemma.", "contents": "Family care for the mentally ill: a new perspective. Family care has been a subject of controversy since large numbers of discharged psychiatric patients have been placed in these homes. The debate has centered on whether such community facilities offer a meaningful alternative in caring for the mentally ill. Findings of a study dealing with the quality of care in the homes and factors deemed responsible for these conditions provide a new perspective on the dilemma."}
{"id": "PMID:230610", "title": "Right-to-left atrial shunt in cardiac dislocation following extensive pneumonectomy.", "content": "Previous reports dealing with cardiac herniation following intrapericardial pneumonectomy illustrate the critical and often lethal hemodynamic sequelae of this complication. In the case presented here, the first and nearly exclusive sign of cardiac herniation after left-sided pneumonectomy with extensive resection of the pericardium was systemic arterial hypoxemia. Subsequent investigations suggested inter-atrial right-to-left shunt in the presence of a patent foramen ovale, caused by slight right-ventricular outflow obstruction with consecutively reversed pressure relationships at atrial level. This explanation was supported by the operative findings, and reversibility was achieved by pericardial reconstruction with parietal pleura. When the patient died 8 months later due to general progression of a mucoepidermoid carcinoma, autopsy confirmed a large patent foramen ovale.", "contents": "Right-to-left atrial shunt in cardiac dislocation following extensive pneumonectomy. Previous reports dealing with cardiac herniation following intrapericardial pneumonectomy illustrate the critical and often lethal hemodynamic sequelae of this complication. In the case presented here, the first and nearly exclusive sign of cardiac herniation after left-sided pneumonectomy with extensive resection of the pericardium was systemic arterial hypoxemia. Subsequent investigations suggested inter-atrial right-to-left shunt in the presence of a patent foramen ovale, caused by slight right-ventricular outflow obstruction with consecutively reversed pressure relationships at atrial level. This explanation was supported by the operative findings, and reversibility was achieved by pericardial reconstruction with parietal pleura. When the patient died 8 months later due to general progression of a mucoepidermoid carcinoma, autopsy confirmed a large patent foramen ovale."}
{"id": "PMID:230611", "title": "HLA-D typing with lymphoblastoid cell lines. VI. Rationale and goals of data reduction.", "content": "This report documents various characteristics of HLA-D typing by mixed leukocyte culture reactions when lymphoblastoid cell lines (LCLs) are substituted for peripheral blood lymphocytes as the stimulator cells. It also provides the rationale for designing the computer program described in the subsequent report. In such experiments, each donor to be HLA-D typed is stimulated with a panel of 30-50 HLA-D homozygous LCLs, each defined HLA-D allele being represented by several different human homogygous typing cells (LCT-HTCs). Variability in the strength of eahc donor's general response and in the strength of stimulation by each LCL-HTC makes it necessary to normalize raw data before the responses of various combinations can be compared and typing responses distinguished from non-typing responses. The autologous response and its equivalent effect among allogenetic combinations, the so-called \"autologous-stimulation\" effect, must also be distinguished from true allogeneic responses. The latter has been accomplished by \"modelling,\" as described in the subsequent report. EBV-negative donors can also be HLA-D typed by this method despite the EBV-positivity of the LCL-HTCs. Preliminary analyses suggest that the HLA-D alleles defined by this method appear to segregate with appropriate haplotypes in family studies.", "contents": "HLA-D typing with lymphoblastoid cell lines. VI. Rationale and goals of data reduction. This report documents various characteristics of HLA-D typing by mixed leukocyte culture reactions when lymphoblastoid cell lines (LCLs) are substituted for peripheral blood lymphocytes as the stimulator cells. It also provides the rationale for designing the computer program described in the subsequent report. In such experiments, each donor to be HLA-D typed is stimulated with a panel of 30-50 HLA-D homozygous LCLs, each defined HLA-D allele being represented by several different human homogygous typing cells (LCT-HTCs). Variability in the strength of eahc donor's general response and in the strength of stimulation by each LCL-HTC makes it necessary to normalize raw data before the responses of various combinations can be compared and typing responses distinguished from non-typing responses. The autologous response and its equivalent effect among allogenetic combinations, the so-called \"autologous-stimulation\" effect, must also be distinguished from true allogeneic responses. The latter has been accomplished by \"modelling,\" as described in the subsequent report. EBV-negative donors can also be HLA-D typed by this method despite the EBV-positivity of the LCL-HTCs. Preliminary analyses suggest that the HLA-D alleles defined by this method appear to segregate with appropriate haplotypes in family studies."}
{"id": "PMID:230612", "title": "Regional specialization in the Malpighian tubules of the New Zealand glow-worm Arachnocampa luminosa (Diptera: mycetophilidae). The structure and function of type I and II cells.", "content": "The Malpighian tubules of the glow-worm Arachnocampa luminosa are divided into four morphologically distinct regions (Parts 1--4) each comprised of a different cell type (Types I--IV). The ultrastructure of Type II cells is indicative of a transport function. The basal cell surface is highly invaginated and at the apical surface the lumen is lined with microvilli about 80% of which contain mitochondria. Spherites contained in these cells are formed from small vesicles produced by the Golgi apparatus. They have a central uric acid core enclosed by laminations of phosphates of calcium and magnesium. Cells of Part 2 of the tubule secrete a fluid high in potassium (173 mM) and low in sodium (18 mM). The cell is 30 mV negative and the lumen 44 mV positive to the bathing solution. This is consistent with the proposal of an apical cation pump. The secretion produced by Part 2 of the tubules is modified by the Type I cells by the reabsorption of potassium (162 mM) and the addition of sodium (24 mM) to the primary excretory fluid. Type I cells are 20 mV negative and the lumen 22 mV positive with respect to the bathing medium. From ultrastructural observations, Type I cells exhibit features characteristic of transporting cells thought to have an absorptive function. The basal and apical cell surfaces are extensively folded, and mitochondria are found in bands above the basal infoldings and below the microvilli. Mitochondria do not penetrate the microvilli. On comparative grounds, the fine structure of Type I cells suggest that they reabsorb ions from the tubule lumen. Energy for these processes may come from the breakdown of lipids by microperoxisomes contained within these cells. Alternatively, the fluid produced by Part 2 of the tubule may be modified passively by diffusional processes across Type I cells.", "contents": "Regional specialization in the Malpighian tubules of the New Zealand glow-worm Arachnocampa luminosa (Diptera: mycetophilidae). The structure and function of type I and II cells. The Malpighian tubules of the glow-worm Arachnocampa luminosa are divided into four morphologically distinct regions (Parts 1--4) each comprised of a different cell type (Types I--IV). The ultrastructure of Type II cells is indicative of a transport function. The basal cell surface is highly invaginated and at the apical surface the lumen is lined with microvilli about 80% of which contain mitochondria. Spherites contained in these cells are formed from small vesicles produced by the Golgi apparatus. They have a central uric acid core enclosed by laminations of phosphates of calcium and magnesium. Cells of Part 2 of the tubule secrete a fluid high in potassium (173 mM) and low in sodium (18 mM). The cell is 30 mV negative and the lumen 44 mV positive to the bathing solution. This is consistent with the proposal of an apical cation pump. The secretion produced by Part 2 of the tubules is modified by the Type I cells by the reabsorption of potassium (162 mM) and the addition of sodium (24 mM) to the primary excretory fluid. Type I cells are 20 mV negative and the lumen 22 mV positive with respect to the bathing medium. From ultrastructural observations, Type I cells exhibit features characteristic of transporting cells thought to have an absorptive function. The basal and apical cell surfaces are extensively folded, and mitochondria are found in bands above the basal infoldings and below the microvilli. Mitochondria do not penetrate the microvilli. On comparative grounds, the fine structure of Type I cells suggest that they reabsorb ions from the tubule lumen. Energy for these processes may come from the breakdown of lipids by microperoxisomes contained within these cells. Alternatively, the fluid produced by Part 2 of the tubule may be modified passively by diffusional processes across Type I cells."}
{"id": "PMID:230613", "title": "Ultrastructural observations on the erythrocytes and thrombocytes of the tuatara, Sphenodon punctatus (Gray).", "content": "The erythrocytes of Sphenodon punctatus (Gray) are nucleated, ellipsoidal and flattened, and contain 55--65 microtubules in their marginal band. The thrombocytes are also flattened, ellipsoidal, nucleated cells and in electron-microscopic preparations occurred in aggregrates. The thrombocytes appeared to be 'activated' and possessed many pseudopodia which were devoid of organelles. The latter were concentrated in the perinuclear region and were encircled by a ring of microtubules. The organelles included ribosomes, mitochondria, membrane--bound dense material and numerous actin-like microfilaments. Cytoplasmic vacuoles contained a moderately dense, filamentous material and/or spheroidal electron-dense inclusions, beta-glycogen particles were scattered in the general cytoplasm and were most concentrated in the pseudopodia. The erythrocytes and thrombocytes of S. punctatus are compared with those in other vertebrates.", "contents": "Ultrastructural observations on the erythrocytes and thrombocytes of the tuatara, Sphenodon punctatus (Gray). The erythrocytes of Sphenodon punctatus (Gray) are nucleated, ellipsoidal and flattened, and contain 55--65 microtubules in their marginal band. The thrombocytes are also flattened, ellipsoidal, nucleated cells and in electron-microscopic preparations occurred in aggregrates. The thrombocytes appeared to be 'activated' and possessed many pseudopodia which were devoid of organelles. The latter were concentrated in the perinuclear region and were encircled by a ring of microtubules. The organelles included ribosomes, mitochondria, membrane--bound dense material and numerous actin-like microfilaments. Cytoplasmic vacuoles contained a moderately dense, filamentous material and/or spheroidal electron-dense inclusions, beta-glycogen particles were scattered in the general cytoplasm and were most concentrated in the pseudopodia. The erythrocytes and thrombocytes of S. punctatus are compared with those in other vertebrates."}
{"id": "PMID:230614", "title": "A scanning electron microscopic study on hepatic changes induced by mouse hepatitis virus-2.", "content": "No significant changes in the structure of the liver were seen until 9 hr after the inoculation of mouse hepatitis virus-2 (MHV-2) into mice. At the 24 hr stage, distinct swelling of hepatocytes and narrowing of sinusoidal lumina were observed from the middle to the central area of the hepatic lobules. Most of the Kupffer cells were swollen. Their villous projections were decreased in number, and the remaining projections became like blebs. Virus particles appeared from this stage in the hepatocytes, the Kupffer cells and the space of Disse. At the 48 hr stage, parenchymal necrotic foci were present in the central and the middle area of the lobules. The necrotic change was increased from 72 hr after inoculation, and was followed by submassive or massive necrosis. It is suggested that hepatic necrosis in both the central and the middle area, or in either area, of the lobules was advanced by aggravation of the sinusoidal microcirculation, as a result of the swelling of the hepatocytes and the Kupffer cells in addition to the direct affection by virus. Fine granulation was observed on the surface of most of the central flagella of the bile duct. Some flagella were degenerated, and came in part to be a fibrillar net.", "contents": "A scanning electron microscopic study on hepatic changes induced by mouse hepatitis virus-2. No significant changes in the structure of the liver were seen until 9 hr after the inoculation of mouse hepatitis virus-2 (MHV-2) into mice. At the 24 hr stage, distinct swelling of hepatocytes and narrowing of sinusoidal lumina were observed from the middle to the central area of the hepatic lobules. Most of the Kupffer cells were swollen. Their villous projections were decreased in number, and the remaining projections became like blebs. Virus particles appeared from this stage in the hepatocytes, the Kupffer cells and the space of Disse. At the 48 hr stage, parenchymal necrotic foci were present in the central and the middle area of the lobules. The necrotic change was increased from 72 hr after inoculation, and was followed by submassive or massive necrosis. It is suggested that hepatic necrosis in both the central and the middle area, or in either area, of the lobules was advanced by aggravation of the sinusoidal microcirculation, as a result of the swelling of the hepatocytes and the Kupffer cells in addition to the direct affection by virus. Fine granulation was observed on the surface of most of the central flagella of the bile duct. Some flagella were degenerated, and came in part to be a fibrillar net."}
{"id": "PMID:230616", "title": "Studies on the tissue-disposition and fate of N-[14C]ethyl-N-nitrosourea in mice.", "content": "The tissue-disposition and fate of N-[14C]ethyl-N-nitrosourea has been studied in mice. A large part of the injected N-[14C]ethyl-N-nitrosourea radioactivity was found to be exhaled as 14CO2. Whole-body autoradiography showed evenly distributed radioactivity in most tissues shortly after the administration of N-[14C]ethyl-N-nitrosourea which probably is due to the homogeneously distributed substance and the non-enzymatically formed ethyl-carbonium ions which have reacted with the tissues. The blood-brain barrier seemed to have a capacity to partially prevent the uptake of the substance in the central nervous system. A high radioactivity was observed in the liver, which may imply that N-[14C]ethyl-N-nitrosourea is enzymatically decomposed in this tissue. An observed labelling of kidneys may be connected with urinary excretion of radioactivity. The radioactivity in the liver and kidney decreased at later survival intervals and a distribution pattern appeared, which was characterized by a labelling of tissues with a high protein or steroid synthesis and of fat containing tissues. The distribution pattern corresponded to the one seen after the administration of [14C]acetaldehyde and is probably due to normal biosynthetic incorporation of radioactivity in the 2-carbon pool. Pretreatments with pyrazole, nialamide and diethyldithiocarbamate caused a marked inhibition of the exhalation of 14CO2 and of the incorporation of radioactivity in the liver. This effect may be directed towards the decomposition of N-[14C]ethyl-N-nitrosourea itself, but an effect on the metabolism of formed 2-carbon fragments is also possible. The incorporation of radioactivity in other tissues was not influenced by the pretreatments.", "contents": "Studies on the tissue-disposition and fate of N-[14C]ethyl-N-nitrosourea in mice. The tissue-disposition and fate of N-[14C]ethyl-N-nitrosourea has been studied in mice. A large part of the injected N-[14C]ethyl-N-nitrosourea radioactivity was found to be exhaled as 14CO2. Whole-body autoradiography showed evenly distributed radioactivity in most tissues shortly after the administration of N-[14C]ethyl-N-nitrosourea which probably is due to the homogeneously distributed substance and the non-enzymatically formed ethyl-carbonium ions which have reacted with the tissues. The blood-brain barrier seemed to have a capacity to partially prevent the uptake of the substance in the central nervous system. A high radioactivity was observed in the liver, which may imply that N-[14C]ethyl-N-nitrosourea is enzymatically decomposed in this tissue. An observed labelling of kidneys may be connected with urinary excretion of radioactivity. The radioactivity in the liver and kidney decreased at later survival intervals and a distribution pattern appeared, which was characterized by a labelling of tissues with a high protein or steroid synthesis and of fat containing tissues. The distribution pattern corresponded to the one seen after the administration of [14C]acetaldehyde and is probably due to normal biosynthetic incorporation of radioactivity in the 2-carbon pool. Pretreatments with pyrazole, nialamide and diethyldithiocarbamate caused a marked inhibition of the exhalation of 14CO2 and of the incorporation of radioactivity in the liver. This effect may be directed towards the decomposition of N-[14C]ethyl-N-nitrosourea itself, but an effect on the metabolism of formed 2-carbon fragments is also possible. The incorporation of radioactivity in other tissues was not influenced by the pretreatments."}
{"id": "PMID:230618", "title": "Effect of phenobarbital on cerebral energy state and metabolism. Enzymatic activities.", "content": "The changes induced by phenobarbital in cerebral enzymatic activities of the Krebs' cycle (citrate synthase, malate dehydrogenase) and electron transfer chain (total NADH-cytochrome c reductase and cytochrome oxidase) were studied. In addition, the activity of lactate dehydrogenase of acetylcholine esterase and of glutamate dehydrogenase was also studied. These enzymatic activities were evaluated in the homogenate in toto and in a crude mitochondrial fraction from rat brain. The modifications in some of these activities indicate that several new metabolic situations occur in brain tissue after phenobarbital treatment.", "contents": "Effect of phenobarbital on cerebral energy state and metabolism. Enzymatic activities. The changes induced by phenobarbital in cerebral enzymatic activities of the Krebs' cycle (citrate synthase, malate dehydrogenase) and electron transfer chain (total NADH-cytochrome c reductase and cytochrome oxidase) were studied. In addition, the activity of lactate dehydrogenase of acetylcholine esterase and of glutamate dehydrogenase was also studied. These enzymatic activities were evaluated in the homogenate in toto and in a crude mitochondrial fraction from rat brain. The modifications in some of these activities indicate that several new metabolic situations occur in brain tissue after phenobarbital treatment."}
{"id": "PMID:230619", "title": "Local versus regional procurement and distribution of granulocytes.", "content": "Granulocyte concentrates obtained by discontinuous flow centrifugation (DFC) and continuous flow centrifugation (CFC) were studied. The DFC granulocytes were obtained from a regional center and stored for 24 hours prior to transfusion. The CFC granulocytes were obtained locally and transfused within a few hours. Even at 24 hours, DFC granulocytes had significantly reduced bactericidal capacity, chemiluminescence, nitroblue tetrazolium reduction, chemotaxis and random mobility. Granulocyte kinetics utilizing DF32P and skin windows demonstrated the ability of DFC granulocytes to circulate and migrate into the tissues despite the in vitro abnormalities. Until effective storage techniques for granulocyte preservation became available, rapid transportation and processing from regional centers or local procurement of granulocytes is necessary to transfuse functional granulocytes.", "contents": "Local versus regional procurement and distribution of granulocytes. Granulocyte concentrates obtained by discontinuous flow centrifugation (DFC) and continuous flow centrifugation (CFC) were studied. The DFC granulocytes were obtained from a regional center and stored for 24 hours prior to transfusion. The CFC granulocytes were obtained locally and transfused within a few hours. Even at 24 hours, DFC granulocytes had significantly reduced bactericidal capacity, chemiluminescence, nitroblue tetrazolium reduction, chemotaxis and random mobility. Granulocyte kinetics utilizing DF32P and skin windows demonstrated the ability of DFC granulocytes to circulate and migrate into the tissues despite the in vitro abnormalities. Until effective storage techniques for granulocyte preservation became available, rapid transportation and processing from regional centers or local procurement of granulocytes is necessary to transfuse functional granulocytes."}
{"id": "PMID:230623", "title": "Single-tissue modeling of decompression schedules.", "content": "This paper deals with the development of a single-tissue model that simulates the uptake and elimination of inert gases by the body of a diver. The model utilizes an effective single tissue with different uptake and elimination time constants to account for the asymmetrical behavior of multiple-tissue human body models. The parameters of this effective tissue are selected according to an optimal strategy that minimizes safe deviation from the decompression requirements recommended by safe practice. The developed strategy is general in nature and can be readily applied to select the optimal parameters for a single-tissue model suitable for any dive regimen on air or mixed gas. As an illustration, the procedure is used to select the optimal tissue that best fits the Standard Air Decompression Tables recommended by the U.S. Navy. The results obtained are in close and safe agreement with the requirements of the U.S. Navy, and consistently fall in the range between the U.S. Navy and the Royal Navy tables.", "contents": "Single-tissue modeling of decompression schedules. This paper deals with the development of a single-tissue model that simulates the uptake and elimination of inert gases by the body of a diver. The model utilizes an effective single tissue with different uptake and elimination time constants to account for the asymmetrical behavior of multiple-tissue human body models. The parameters of this effective tissue are selected according to an optimal strategy that minimizes safe deviation from the decompression requirements recommended by safe practice. The developed strategy is general in nature and can be readily applied to select the optimal parameters for a single-tissue model suitable for any dive regimen on air or mixed gas. As an illustration, the procedure is used to select the optimal tissue that best fits the Standard Air Decompression Tables recommended by the U.S. Navy. The results obtained are in close and safe agreement with the requirements of the U.S. Navy, and consistently fall in the range between the U.S. Navy and the Royal Navy tables."}
{"id": "PMID:230620", "title": "Studies of donors who transmit posttransfusion hepatitis.", "content": "Sera and questionnaires were evaluated retrospectively from 128 volunteer blood donors whose blood had been implicated in cases of clinically recognized post-transfusion hepatitis in recipients of one- or two-unit blood transfusion between 1971 and 1977. Serologic markers of hepatitis B virus (HBV) infection were found in 23 percent, compared to 9.7 percent of 3,230 prospective blood donors. The prevalence of antibody to hepatitis A virus was similar among implicated donors (44%), prospective donors (58%), and among those implicated donors with (41%) and without (44%) HBV markers. Among implicated donors, none had a history at the time of donation of having had clinically recognizable hepatitis, 93 percent had no history of prior blood transfusion, and 80 percent had normal hepatic enzymes. Data from this study confirm that non-A, non-B hepatitis has been a common form of posttransfusion hepatitis in recent years, since 77 percent of these implicated donors had no HBV serologic markers. In addition, these donors could not be distinguished by age, race, sex, history of clinical hepatitis or of prior blood transfusion, or in most cases by hepatic enzyme levels.", "contents": "Studies of donors who transmit posttransfusion hepatitis. Sera and questionnaires were evaluated retrospectively from 128 volunteer blood donors whose blood had been implicated in cases of clinically recognized post-transfusion hepatitis in recipients of one- or two-unit blood transfusion between 1971 and 1977. Serologic markers of hepatitis B virus (HBV) infection were found in 23 percent, compared to 9.7 percent of 3,230 prospective blood donors. The prevalence of antibody to hepatitis A virus was similar among implicated donors (44%), prospective donors (58%), and among those implicated donors with (41%) and without (44%) HBV markers. Among implicated donors, none had a history at the time of donation of having had clinically recognizable hepatitis, 93 percent had no history of prior blood transfusion, and 80 percent had normal hepatic enzymes. Data from this study confirm that non-A, non-B hepatitis has been a common form of posttransfusion hepatitis in recent years, since 77 percent of these implicated donors had no HBV serologic markers. In addition, these donors could not be distinguished by age, race, sex, history of clinical hepatitis or of prior blood transfusion, or in most cases by hepatic enzyme levels."}
{"id": "PMID:230621", "title": "Clinical results on the use of human ceruloplasmin in aplastic anemia.", "content": "Frequent blood transfusions are necessary in aplastic anemia because of decreased hematopoietic function. In order to maintain the hemoglobin level and to decrease the need for blood transfusion, human ceruloplasmin was used for the treatment of 73 patients with aplastic anemia. A marked beneficial effect was obtained in 16 cases. The treatment was moderately effective in 17 cases, slightly effective in eight cases, and ineffective in 32 cases. The usual dose of ceruloplasmin was 15 mg/day, but it was varied according to symptoms. Side effects were minimal when ceruloplasmin was administered by slow intravenous injection.", "contents": "Clinical results on the use of human ceruloplasmin in aplastic anemia. Frequent blood transfusions are necessary in aplastic anemia because of decreased hematopoietic function. In order to maintain the hemoglobin level and to decrease the need for blood transfusion, human ceruloplasmin was used for the treatment of 73 patients with aplastic anemia. A marked beneficial effect was obtained in 16 cases. The treatment was moderately effective in 17 cases, slightly effective in eight cases, and ineffective in 32 cases. The usual dose of ceruloplasmin was 15 mg/day, but it was varied according to symptoms. Side effects were minimal when ceruloplasmin was administered by slow intravenous injection."}
{"id": "PMID:230631", "title": "[Electrophoretic determination of lipoproteins in the blood of dogs after the administration of beta,beta'-dichlorodiethylsulfide].", "content": "The effect of a single administration of beta,beta'-dichlorodiethylsulphide at a dose of 35 mg per kg b. w. was studied, as exerted on the level of serum lipoproteins. The blood of experimental dogs showed a significant rise of alpha 3 lipoproteins, reaching its maximum 24 hours after the administration of the substance. During the studied period, the alpha-fraction lipoprotein gradually shifted to the beta-fraction terminating before the exitus.", "contents": "[Electrophoretic determination of lipoproteins in the blood of dogs after the administration of beta,beta'-dichlorodiethylsulfide]. The effect of a single administration of beta,beta'-dichlorodiethylsulphide at a dose of 35 mg per kg b. w. was studied, as exerted on the level of serum lipoproteins. The blood of experimental dogs showed a significant rise of alpha 3 lipoproteins, reaching its maximum 24 hours after the administration of the substance. During the studied period, the alpha-fraction lipoprotein gradually shifted to the beta-fraction terminating before the exitus."}
{"id": "PMID:230634", "title": "Detection of hepatitis B surface antigen in fixed tissues of patients with cirrhosis and hepatoma.", "content": "HBsAg has been sought by light microscopy in liver specimens from patients with cirrhosis (79 cases) and hepatoma (99 cases). The study was carried out on fixed material using orcein staining, immunoperoxidase technique and indirect immunofluorescence. HBsAg was detected in the serum by radio-immunoassay (RIA) using Ausria II-125 in 38 patients with cirrhosis and in 36 with hepatoma. In the 38 seropositive cases of cirrhosis HBsAg-positive cells were observed in 31 (81.6%) by the orcein staining and in 32 (84.2%) by the peroxidase and immunofluorescence staining. Among the 36 seropositive patients with hepatoma, HBsAg was detected in the surrounding non-neoplastic part of the liver, cirrhotic or not, in 30 (83.3%) by orcein staining and in 34 (94.4%) by the immunoperoxidase method and immunofluorescence. Positive solitary-cells were seen occasionally in the tumor tissue in 16 cases using orcein, in 9 using peroxidase and in 7 by fluorescence, out of the 36 seropositive patients with hepatoma. The results of this study do not support the hypothesis of a direct oncogenic effect of HBsAg on the liver cells, since this antigen was detected mainly in the non-neoplastic part of the liver tissue and only occasionally in the tumor cells. Of the 63 cases of seronegative hepatoma, 3 showed some round orcein-positive inclusion bodies in the cytoplasm of the neoplastic and the non-neoplastic cells; these bodies were not stained by the two immunological methods.", "contents": "Detection of hepatitis B surface antigen in fixed tissues of patients with cirrhosis and hepatoma. HBsAg has been sought by light microscopy in liver specimens from patients with cirrhosis (79 cases) and hepatoma (99 cases). The study was carried out on fixed material using orcein staining, immunoperoxidase technique and indirect immunofluorescence. HBsAg was detected in the serum by radio-immunoassay (RIA) using Ausria II-125 in 38 patients with cirrhosis and in 36 with hepatoma. In the 38 seropositive cases of cirrhosis HBsAg-positive cells were observed in 31 (81.6%) by the orcein staining and in 32 (84.2%) by the peroxidase and immunofluorescence staining. Among the 36 seropositive patients with hepatoma, HBsAg was detected in the surrounding non-neoplastic part of the liver, cirrhotic or not, in 30 (83.3%) by orcein staining and in 34 (94.4%) by the immunoperoxidase method and immunofluorescence. Positive solitary-cells were seen occasionally in the tumor tissue in 16 cases using orcein, in 9 using peroxidase and in 7 by fluorescence, out of the 36 seropositive patients with hepatoma. The results of this study do not support the hypothesis of a direct oncogenic effect of HBsAg on the liver cells, since this antigen was detected mainly in the non-neoplastic part of the liver tissue and only occasionally in the tumor cells. Of the 63 cases of seronegative hepatoma, 3 showed some round orcein-positive inclusion bodies in the cytoplasm of the neoplastic and the non-neoplastic cells; these bodies were not stained by the two immunological methods."}
{"id": "PMID:230639", "title": "Epstein-Barr virus infection in polytransfused patients with homozygous beta-thalassaemia.", "content": "The frequency of Epstein-Barr virus (EBV) and hepatitis B virus (HBV) infection has been studied in 149 polytransfused thalassaemic patients and in healthy controls. Evidence for EBV infection was based on the detection of antibodies to viral capsid antigen (anti-VCA) and for HBV infection on the detection of either hepatitis B surface antigen (HBsAg) or hepatitis B surface antibody (anti-HBs). The frequency of anti-VCA was not significantly higher in the patients (16.4%) compared to the controls (69.8%) whereas HBV infection was more frequently observed in the patients (91.3%) than in the controls (17.3%). There was also no evidence of repeated infection or recent infection with EBV in the polytransfused patients. These data suggest that transfusion of stored blood does not represent a significant factor of spread for EBV.", "contents": "Epstein-Barr virus infection in polytransfused patients with homozygous beta-thalassaemia. The frequency of Epstein-Barr virus (EBV) and hepatitis B virus (HBV) infection has been studied in 149 polytransfused thalassaemic patients and in healthy controls. Evidence for EBV infection was based on the detection of antibodies to viral capsid antigen (anti-VCA) and for HBV infection on the detection of either hepatitis B surface antigen (HBsAg) or hepatitis B surface antibody (anti-HBs). The frequency of anti-VCA was not significantly higher in the patients (16.4%) compared to the controls (69.8%) whereas HBV infection was more frequently observed in the patients (91.3%) than in the controls (17.3%). There was also no evidence of repeated infection or recent infection with EBV in the polytransfused patients. These data suggest that transfusion of stored blood does not represent a significant factor of spread for EBV."}
{"id": "PMID:230635", "title": "Some results obtained in the \"Stefan S. Nicolau\" Institute of Virology by the study of herpes simplex virus.", "content": "The results obtained in the \"Stefan S. Nicolau\" Institute of Virology by the study of herpes simplex virus (HSV) are reviewed. The investigations were mainly focused on HSV biology, genetic markers, experimental HSV infection, correlation between HSV and some diseases, action of some chemical and biological preparations on HSV, in vitro and in vivo HSV oncogenicity, HSV-induced surface antigens, a.o.", "contents": "Some results obtained in the \"Stefan S. Nicolau\" Institute of Virology by the study of herpes simplex virus. The results obtained in the \"Stefan S. Nicolau\" Institute of Virology by the study of herpes simplex virus (HSV) are reviewed. The investigations were mainly focused on HSV biology, genetic markers, experimental HSV infection, correlation between HSV and some diseases, action of some chemical and biological preparations on HSV, in vitro and in vivo HSV oncogenicity, HSV-induced surface antigens, a.o."}
{"id": "PMID:230636", "title": "Results in the study of virus--tumor relationships obtained in the \"Stefan S. Nicolau\" Institute of Virology.", "content": "The results of over 200 scientific papers in the field of in vivo and in vitro virus--tumor relationships, worked out in the \"Stefan S. Nicolau\" Institute of Virology during a period of over 25 years, are very briefly reviewed. Stress is laid on the original theoretical and practical contributions of the institute to the knowledge of viral carcinogenesis in animals and humans. Some personal viewpoints in the interpretation of results are presented and new research prospects in this field--which represents a traditional concern of the institute--are lutlined.", "contents": "Results in the study of virus--tumor relationships obtained in the \"Stefan S. Nicolau\" Institute of Virology. The results of over 200 scientific papers in the field of in vivo and in vitro virus--tumor relationships, worked out in the \"Stefan S. Nicolau\" Institute of Virology during a period of over 25 years, are very briefly reviewed. Stress is laid on the original theoretical and practical contributions of the institute to the knowledge of viral carcinogenesis in animals and humans. Some personal viewpoints in the interpretation of results are presented and new research prospects in this field--which represents a traditional concern of the institute--are lutlined."}
{"id": "PMID:230644", "title": "[Physicochemical properties of the Teschen disease virus].", "content": "The physical stability of Teschen disease virus (TDV) was tested. It was found that 8 M urea at 37 degrees C and 0.5% Tween-20 for 1-2 hours destroyed TDV with formation of morphologically distinct subunits. The morphology of TDV virions and its subunits formed under the effect of urea and Tween-20 was studied. Sedimentation constant (120 S) and the polypeptide composition of TDV were determined. In TDV, major polypeptides (VP1 less than or equal to 4) and minor polypeptides (VP1m and VP2m) were found their molecular weights being 82,000, 67,000, 35,000, 30,000, 77,000, and 46,000 daltons respectively.", "contents": "[Physicochemical properties of the Teschen disease virus]. The physical stability of Teschen disease virus (TDV) was tested. It was found that 8 M urea at 37 degrees C and 0.5% Tween-20 for 1-2 hours destroyed TDV with formation of morphologically distinct subunits. The morphology of TDV virions and its subunits formed under the effect of urea and Tween-20 was studied. Sedimentation constant (120 S) and the polypeptide composition of TDV were determined. In TDV, major polypeptides (VP1 less than or equal to 4) and minor polypeptides (VP1m and VP2m) were found their molecular weights being 82,000, 67,000, 35,000, 30,000, 77,000, and 46,000 daltons respectively."}
{"id": "PMID:230645", "title": "[Etiological role of the herpes simplex virus in causing cervical cancer].", "content": "The results of the composite virological and immunological examinations of 46 patients with cervical carcinoma (CC) attest to the association of herpes simplex virus (HSV) with neoplastic processes. HSV strains were isolated from the tumour tissue as well as from the cervical canal secretions and blood of 4 patients. A higher level of virus-neutralizing and complement-fixing antibodies to HSV was found in sera from CC patients as compared with the control group of normal women. Antibody to HSV type 2 was found in 38.8% of sera from the patients and 12.6% in the control group. Lymphocytes from CC patients induced blasttransformation reaction to HSV twice as frequently as those from healthy subjects. The virus-specific antigen was found in tumour cells of 36% CC patients in immunofluorescent examinations of smears from the cervix. The presented results are related to the determination of the etiological role of HSV in cervical carcinoma.", "contents": "[Etiological role of the herpes simplex virus in causing cervical cancer]. The results of the composite virological and immunological examinations of 46 patients with cervical carcinoma (CC) attest to the association of herpes simplex virus (HSV) with neoplastic processes. HSV strains were isolated from the tumour tissue as well as from the cervical canal secretions and blood of 4 patients. A higher level of virus-neutralizing and complement-fixing antibodies to HSV was found in sera from CC patients as compared with the control group of normal women. Antibody to HSV type 2 was found in 38.8% of sera from the patients and 12.6% in the control group. Lymphocytes from CC patients induced blasttransformation reaction to HSV twice as frequently as those from healthy subjects. The virus-specific antigen was found in tumour cells of 36% CC patients in immunofluorescent examinations of smears from the cervix. The presented results are related to the determination of the etiological role of HSV in cervical carcinoma."}
{"id": "PMID:230650", "title": "[Scintigraphic study of the sacroiliac joints].", "content": "Scintigraphic and radiometric investigation with 99mTc-pyrophosphate was carried out on the sacro-iliac joints of 79 patients: 48 with positive form of Behterev disease, 26 -- with probable form of the disease, 2 -- with Reiter syndrome and 2 -- with rheumatoid arthritis. Scintigraphy was combined with radiometric investigation (determination of sacro-iliac -- sacral index) with a view to obtaining quantitative information about the degree of accumulation of pyrophosphate in sacro-iliac joints. The data from the scintigraphic and radiometric investigations were juxaposed to clinical laboratory and X-ray investigations. Forty of the patients examined were HLA-B27 positive and 38 of them-HLA-B27 negative. Sacro-iliac index, determined in 13 healthy subjects (26 sacro-iliac joints) was within the limits of 1.18 +/- 0.094. The average value of the index of the 78 patients examined was 1.41 +/- 0.20. The index, during the first and second X-ray stage was 1.43 +/- 0.13 and 1.45 +/- 0.19 resp. The values decreased to 1.39 +/- 0.18 during the third X-ray stage, whereas in the fourth stage with completely ankylosis of the joints, the index was 1.20 +/- 0.07, being close to that of the control group of healthy subjects.", "contents": "[Scintigraphic study of the sacroiliac joints]. Scintigraphic and radiometric investigation with 99mTc-pyrophosphate was carried out on the sacro-iliac joints of 79 patients: 48 with positive form of Behterev disease, 26 -- with probable form of the disease, 2 -- with Reiter syndrome and 2 -- with rheumatoid arthritis. Scintigraphy was combined with radiometric investigation (determination of sacro-iliac -- sacral index) with a view to obtaining quantitative information about the degree of accumulation of pyrophosphate in sacro-iliac joints. The data from the scintigraphic and radiometric investigations were juxaposed to clinical laboratory and X-ray investigations. Forty of the patients examined were HLA-B27 positive and 38 of them-HLA-B27 negative. Sacro-iliac index, determined in 13 healthy subjects (26 sacro-iliac joints) was within the limits of 1.18 +/- 0.094. The average value of the index of the 78 patients examined was 1.41 +/- 0.20. The index, during the first and second X-ray stage was 1.43 +/- 0.13 and 1.45 +/- 0.19 resp. The values decreased to 1.39 +/- 0.18 during the third X-ray stage, whereas in the fourth stage with completely ankylosis of the joints, the index was 1.20 +/- 0.07, being close to that of the control group of healthy subjects."}
{"id": "PMID:230651", "title": "REM sleep, stress and search activity. A short critical review and a new conception.", "content": "Basing themselves on an analysis of data cited by other researchers and the results of their own investigation, conducted on man and animals, the authors disclose that sleep changes are determined by the type of behavioural reaction to emotional stress: the behaviour that includes components of search activity directed at changing the situation is accompanied by a reduction of REM sleep time; renunciation of search, as in the cases of passive avoidance, neurotic anxiety and depression, is attended by an increase in REM sleep requirement. Presumably, the function of REM sleep is to compensate for renunciation of search in the waking period. The authors suggest a method of appraising the character of reaction to stress by sleep changes--calculation of the time ratio of REM sleep to delta-sleep in the first two cycles.", "contents": "REM sleep, stress and search activity. A short critical review and a new conception. Basing themselves on an analysis of data cited by other researchers and the results of their own investigation, conducted on man and animals, the authors disclose that sleep changes are determined by the type of behavioural reaction to emotional stress: the behaviour that includes components of search activity directed at changing the situation is accompanied by a reduction of REM sleep time; renunciation of search, as in the cases of passive avoidance, neurotic anxiety and depression, is attended by an increase in REM sleep requirement. Presumably, the function of REM sleep is to compensate for renunciation of search in the waking period. The authors suggest a method of appraising the character of reaction to stress by sleep changes--calculation of the time ratio of REM sleep to delta-sleep in the first two cycles."}
{"id": "PMID:230652", "title": "Maturation of REM-patterns from childhood to maturity.", "content": "The operational value of measuring paradoxical sleep (PS) as a percentage of total sleeping time has been questioned. The purpose of this study was to determine the interactions between the variations in hormonal secretions and paradoxical sleep in women of different age-groups. Three parameters were utilized: REM-percent, REM-density and the eye movement frequencies. The distribution of the time-intervals between the oculomotor signals as indicated by the ratio of the higher to the lower eye movement frequencies gives a clue as to the significance of the spatio-temporal organization of the brain-signals during paradoxical sleep. This notion introduces an internal temporal and dynamic dimension in the concept of REM or Paradoxical Sleep. From our results it appears that the changes in the ratio between the different types of oculomotor discharges are a function not only of hormonal fluctuations but also of age. This point of view opens a new possibility of interpreting the results.", "contents": "Maturation of REM-patterns from childhood to maturity. The operational value of measuring paradoxical sleep (PS) as a percentage of total sleeping time has been questioned. The purpose of this study was to determine the interactions between the variations in hormonal secretions and paradoxical sleep in women of different age-groups. Three parameters were utilized: REM-percent, REM-density and the eye movement frequencies. The distribution of the time-intervals between the oculomotor signals as indicated by the ratio of the higher to the lower eye movement frequencies gives a clue as to the significance of the spatio-temporal organization of the brain-signals during paradoxical sleep. This notion introduces an internal temporal and dynamic dimension in the concept of REM or Paradoxical Sleep. From our results it appears that the changes in the ratio between the different types of oculomotor discharges are a function not only of hormonal fluctuations but also of age. This point of view opens a new possibility of interpreting the results."}
{"id": "PMID:230648", "title": "[Design of inactivated polyvalent antiherpes vaccines].", "content": "The variants of inactivated vaccine against herpes simplex virus have been developed: 1, 2 and 1 + 2. The first two variants consist of 5 different strains of herpes virus of the appropriate type, and the third variant of their mixture. The strains differ in their antigenic and biological characteristics. Complete inactivation of the virus suspension was achieved by treatment of the vaccine with formalin. Herpes vaccines were used for immunization of 477 patients with frequently relapsing forms of herpes of different localizations. The therapeutic-prophylactic effect of these vaccines indicates their relatively high efficacy: by the end of 9 months favourable results exceeded 95%. Better results were obtained with HSV-1 vaccine. A second cycle of immunization given to some patients resulted in markedly positive effect.", "contents": "[Design of inactivated polyvalent antiherpes vaccines]. The variants of inactivated vaccine against herpes simplex virus have been developed: 1, 2 and 1 + 2. The first two variants consist of 5 different strains of herpes virus of the appropriate type, and the third variant of their mixture. The strains differ in their antigenic and biological characteristics. Complete inactivation of the virus suspension was achieved by treatment of the vaccine with formalin. Herpes vaccines were used for immunization of 477 patients with frequently relapsing forms of herpes of different localizations. The therapeutic-prophylactic effect of these vaccines indicates their relatively high efficacy: by the end of 9 months favourable results exceeded 95%. Better results were obtained with HSV-1 vaccine. A second cycle of immunization given to some patients resulted in markedly positive effect."}
{"id": "PMID:230646", "title": "[Viral interaction with stimulated and nonstimulated human tonsil cells].", "content": "Interferon induction and the course of infection with paramyxovirus (Newcastle disease virus) and alphaviruses (Venezuelan equine encephalomyelitis, Sindbis, Semliki forest viruses) in human tonsillar cell cultures were studied in comparison with continuous Burkitt lymphoma, Raji, and Nawalva cells. The virus inducers stimulated production of dozens and hundreds IU50/ml of interferon in tonsillar cell cultures. No virus replication could be detected either in intact or phytohemagglutinin-stimulated tonsillar cells. Phytohemagglutinin treatment may lead to blocking of interferon production induced by Newcastle disease virus.", "contents": "[Viral interaction with stimulated and nonstimulated human tonsil cells]. Interferon induction and the course of infection with paramyxovirus (Newcastle disease virus) and alphaviruses (Venezuelan equine encephalomyelitis, Sindbis, Semliki forest viruses) in human tonsillar cell cultures were studied in comparison with continuous Burkitt lymphoma, Raji, and Nawalva cells. The virus inducers stimulated production of dozens and hundreds IU50/ml of interferon in tonsillar cell cultures. No virus replication could be detected either in intact or phytohemagglutinin-stimulated tonsillar cells. Phytohemagglutinin treatment may lead to blocking of interferon production induced by Newcastle disease virus."}
{"id": "PMID:230654", "title": "Influence of arginine vasotocin administration on nocturnal sleep of human subjects.", "content": "Arginine vasotocin (AVT) or placebo were subcutaneously administered to 4 men at 22.00 and 01.00 h, along four nights, and polygraphic recordings were performed between 22.00 and 02.00 h during sleep. AVT significantly increased only the amount of rapid eye movement (REM) sleep (p less than 0.05), but did not influence the latency of the first REM sleep period. This effect of AVT was not dose dependent in the range between 2 and 12 microgram AVT. AVT or placebo were also intravenously injected or perfused to 10 normal adult subjects, at different times of the day, under clinical control. Doses between 2 microgram perfused 4 h and 12 microgram perfused 30 min, did not produce clinical signs of sleep. It is suggested that AVT is not a blood factor for inducing of slow waves sleep (SWS) or REM sleep in humans.", "contents": "Influence of arginine vasotocin administration on nocturnal sleep of human subjects. Arginine vasotocin (AVT) or placebo were subcutaneously administered to 4 men at 22.00 and 01.00 h, along four nights, and polygraphic recordings were performed between 22.00 and 02.00 h during sleep. AVT significantly increased only the amount of rapid eye movement (REM) sleep (p less than 0.05), but did not influence the latency of the first REM sleep period. This effect of AVT was not dose dependent in the range between 2 and 12 microgram AVT. AVT or placebo were also intravenously injected or perfused to 10 normal adult subjects, at different times of the day, under clinical control. Doses between 2 microgram perfused 4 h and 12 microgram perfused 30 min, did not produce clinical signs of sleep. It is suggested that AVT is not a blood factor for inducing of slow waves sleep (SWS) or REM sleep in humans."}
{"id": "PMID:230668", "title": "[Study of sensitivity using sinusoidally modulated currents].", "content": "A quantitative examination of sensitivity with using modulated sinosoidal currents was carried out in 10 healthy individuals and 44 patients with various disorders of the central and peripheral nervous system. In the healthy probands the magnitudes of the current force causing the specific sensation under the electrodes in various body regions were determined. A substantial, statistically significant rise of the current perception threshold was revealed in patients with superficial sensitivity disturbances. In patients with deep sensitivity disturbances both quantitative and qualitative distinctions were discovered.", "contents": "[Study of sensitivity using sinusoidally modulated currents]. A quantitative examination of sensitivity with using modulated sinosoidal currents was carried out in 10 healthy individuals and 44 patients with various disorders of the central and peripheral nervous system. In the healthy probands the magnitudes of the current force causing the specific sensation under the electrodes in various body regions were determined. A substantial, statistically significant rise of the current perception threshold was revealed in patients with superficial sensitivity disturbances. In patients with deep sensitivity disturbances both quantitative and qualitative distinctions were discovered."}
{"id": "PMID:230670", "title": "[Zinc activated tartrate resistent phosphatases in the brains of different animal species and their characterization].", "content": "A zinc activated tartrate resistent phosphatase (ZnTP) of the brain of different animal species was separated by electrofocusing in polyacrylamide gels. It is demonstrable selectively in the presence of 20 mM zinc acetate and 10 mM D,L-sodium tartrate or of 100 mM zinc acetate only. The ZnTP hydrolyzes 1-naphthyl phosphate and 4-nitrophenyl phosphate, respectively. High activity of ZnTP is evident in the brains of rats and rabbits. The activity is moderate or absent in the brains of mice, syrian-hamsters, sheeps, cats, rhesus monkeys, and of human beings. The isoelectric points of the enzyme from the various species are different, but the molecular weight is identical (65 000 estimated by gelfiltration on Sephadex G 100 in the brain of rat, rabbit, syrian-hamster, and man). A method of quantitative evaluation of ZnTP activity is described.", "contents": "[Zinc activated tartrate resistent phosphatases in the brains of different animal species and their characterization]. A zinc activated tartrate resistent phosphatase (ZnTP) of the brain of different animal species was separated by electrofocusing in polyacrylamide gels. It is demonstrable selectively in the presence of 20 mM zinc acetate and 10 mM D,L-sodium tartrate or of 100 mM zinc acetate only. The ZnTP hydrolyzes 1-naphthyl phosphate and 4-nitrophenyl phosphate, respectively. High activity of ZnTP is evident in the brains of rats and rabbits. The activity is moderate or absent in the brains of mice, syrian-hamsters, sheeps, cats, rhesus monkeys, and of human beings. The isoelectric points of the enzyme from the various species are different, but the molecular weight is identical (65 000 estimated by gelfiltration on Sephadex G 100 in the brain of rat, rabbit, syrian-hamster, and man). A method of quantitative evaluation of ZnTP activity is described."}
{"id": "PMID:230671", "title": "Further characterization of the polyoma virus Y8e from a Rauscher leukaemia virus producing mouse cell line and detection of partial sequence homology between polyoma virus Y8eDNA and hamster papovavirus DNA.", "content": "A DNA virus of the papovavirus group spontaneously appeared in RLV-infected spleen and thymus cells of mice in vitro was further characterized as polyoma virus Y8e by haemagglutination test, banding in density gradients, sedimentation coefficients of DNA and molecular hybridization of its DNA. The latter technique showed nearly complete sequence homology to polyoma virus strain SE DNA, partial sequence homology to hamster papovavirus DNA and mouse host DNA and little or no sequence homology to SV 40 DNA. The relationship between rodent papovaviruses and primate papovaviruses is discussed.", "contents": "Further characterization of the polyoma virus Y8e from a Rauscher leukaemia virus producing mouse cell line and detection of partial sequence homology between polyoma virus Y8eDNA and hamster papovavirus DNA. A DNA virus of the papovavirus group spontaneously appeared in RLV-infected spleen and thymus cells of mice in vitro was further characterized as polyoma virus Y8e by haemagglutination test, banding in density gradients, sedimentation coefficients of DNA and molecular hybridization of its DNA. The latter technique showed nearly complete sequence homology to polyoma virus strain SE DNA, partial sequence homology to hamster papovavirus DNA and mouse host DNA and little or no sequence homology to SV 40 DNA. The relationship between rodent papovaviruses and primate papovaviruses is discussed."}
{"id": "PMID:230673", "title": "Synthesis of spontaneous interferon by mouse peritoneal cells in vitro. I. Attempts to elucidate the origin of spontaneous interferon.", "content": "Interferon-like substance has been obtained in the media of mice 129/AoBoy peritoneal cell cultures after incubation at 26 degrees C. The substance showed characteristics that permitted it to be accepted as an interferon. Looking for the presence (in the media or in the sera) of infectious agents responsible for this event experiments were performed that excluded this possibility. Peritoneal cells cultures in media without calf sera (MEM, PBS) produced spontaneous interferon, too. In the same medium the peritoneal cells from various mouse strains differed in the capacity to spontaneous interferon formation. Finally it was found that the level of this interferon was raised with the age of mice.", "contents": "Synthesis of spontaneous interferon by mouse peritoneal cells in vitro. I. Attempts to elucidate the origin of spontaneous interferon. Interferon-like substance has been obtained in the media of mice 129/AoBoy peritoneal cell cultures after incubation at 26 degrees C. The substance showed characteristics that permitted it to be accepted as an interferon. Looking for the presence (in the media or in the sera) of infectious agents responsible for this event experiments were performed that excluded this possibility. Peritoneal cells cultures in media without calf sera (MEM, PBS) produced spontaneous interferon, too. In the same medium the peritoneal cells from various mouse strains differed in the capacity to spontaneous interferon formation. Finally it was found that the level of this interferon was raised with the age of mice."}
{"id": "PMID:230669", "title": "[Extension of pituitary adenomas into the cavernous sinuses (clinico-anatomic study)].", "content": "The article deals with the study of 288 verified cases with adenomas of the pituitary gland. Growth of the tumor into the cavernous sinus was revealed in 102 cases (35.4%). The possible routes of penetration of pituitary tumours into the cavernous sinus and the relationship of the new growths with the intracavernous structures are described in detail. The findings of purposeful radio-diagnostic examination revealing the characteristic combinations of the symptoms of intracavernous expansion of the tumor are of paramount importance in recognizing growth of pituitary adenomas into the cavernous sinuses. It is emphasized that the possibility of such growth must be borne in mind when the operation is planned.", "contents": "[Extension of pituitary adenomas into the cavernous sinuses (clinico-anatomic study)]. The article deals with the study of 288 verified cases with adenomas of the pituitary gland. Growth of the tumor into the cavernous sinus was revealed in 102 cases (35.4%). The possible routes of penetration of pituitary tumours into the cavernous sinus and the relationship of the new growths with the intracavernous structures are described in detail. The findings of purposeful radio-diagnostic examination revealing the characteristic combinations of the symptoms of intracavernous expansion of the tumor are of paramount importance in recognizing growth of pituitary adenomas into the cavernous sinuses. It is emphasized that the possibility of such growth must be borne in mind when the operation is planned."}
{"id": "PMID:230674", "title": "Production of antiviral and migration inhibitory activities in the peritoneum of mice after inoculation with allogenic Ehrlich ascites tumor cells.", "content": "Peritoneal inoculation of Ehrlich ascites cells into mice stimulates the appearance of migration inhibitory factor (MIF) not only in the peritoneum but also in the circulation of mice. Whereas the MIF-activity in the peritoneum reached maximum at 6 days and disappeared within 17 days, the MIF-activity of sera reached maximum levels at about 11 days after intraperitoneal inoculation of tumor cells (10(6) of EAC per mouse). In addition, an antiviral activity of peritoneal exudates was observed in the early stage (24--72 h) of tumor challenge. The time-course of appearance of both MIF and AV-inhibitor are presented. A significant decrease of MIF-activity was noted when the tumor-inoculated mice were treated with ds-RNA, antithymocyte serum and cyclophosphamide, respectively. The appearance of antiviral activity in the peritoneum of tumor-inoculated mice seems to be macrophage-dependent. Although the antiviral factor meets several criteria of interferons, further studies are required for its characterization.", "contents": "Production of antiviral and migration inhibitory activities in the peritoneum of mice after inoculation with allogenic Ehrlich ascites tumor cells. Peritoneal inoculation of Ehrlich ascites cells into mice stimulates the appearance of migration inhibitory factor (MIF) not only in the peritoneum but also in the circulation of mice. Whereas the MIF-activity in the peritoneum reached maximum at 6 days and disappeared within 17 days, the MIF-activity of sera reached maximum levels at about 11 days after intraperitoneal inoculation of tumor cells (10(6) of EAC per mouse). In addition, an antiviral activity of peritoneal exudates was observed in the early stage (24--72 h) of tumor challenge. The time-course of appearance of both MIF and AV-inhibitor are presented. A significant decrease of MIF-activity was noted when the tumor-inoculated mice were treated with ds-RNA, antithymocyte serum and cyclophosphamide, respectively. The appearance of antiviral activity in the peritoneum of tumor-inoculated mice seems to be macrophage-dependent. Although the antiviral factor meets several criteria of interferons, further studies are required for its characterization."}
{"id": "PMID:230675", "title": "Production of human leukocyte interferon for clinical use under immunoelectrophoretic control.", "content": "Human leukocyte interferon (HLIF) can be contaminated by several antigens which may include also potentially pathogenic agents. For this reason, gel filtration as a separation method was included into the routine procedure of preparation and purification of HLIF for clinical use. Since production of HLIF requires the cultivation of leukocytes in the presence of serum (or albumin), serum proteins represent then the majority of proteins contaminating IF preparations. Measuring the total protein content, as a control of various antigens present in HLIF preparations during purification, becomes ineffective because, essentially, it indicates only the decrease of the amount of proteins derived from cultivation medium. For a better visualization of dissociation of different antigens from molecules with IF activity during the purification procedure, the method of quantitative immunoelectrophoresis was applied utilizing a sheep antiinterferon serum in assay. Our results indicate that this method represents a valuable control test.", "contents": "Production of human leukocyte interferon for clinical use under immunoelectrophoretic control. Human leukocyte interferon (HLIF) can be contaminated by several antigens which may include also potentially pathogenic agents. For this reason, gel filtration as a separation method was included into the routine procedure of preparation and purification of HLIF for clinical use. Since production of HLIF requires the cultivation of leukocytes in the presence of serum (or albumin), serum proteins represent then the majority of proteins contaminating IF preparations. Measuring the total protein content, as a control of various antigens present in HLIF preparations during purification, becomes ineffective because, essentially, it indicates only the decrease of the amount of proteins derived from cultivation medium. For a better visualization of dissociation of different antigens from molecules with IF activity during the purification procedure, the method of quantitative immunoelectrophoresis was applied utilizing a sheep antiinterferon serum in assay. Our results indicate that this method represents a valuable control test."}
{"id": "PMID:230678", "title": "Antiviral and anticellular effects of interferon on the mouse embryonic cells transformed by viruses and/or chemical carcinogen.", "content": "The antiviral and anticellular activity of partially purified mouse interferon has been tested in cell lines transformed with Simian Virus 40 (MEB-SV 40), mouse sarcoma virus (Harvey strain) (MEB-MSV), and 20-methylcholanthrene (MEB-MCH), respectively. The transformed lines were derived from C3H mouse embryonic primary cells. It has been shown that the MEB-MSV cells were 10 to 50 times less sensitive to the antiviral effect of interferon than the MEB-SV 40 or MEB-MCH cells. A 30% reduction of the number of treated cells as compared with untreated control cells was taken as basis for comparison of anticellular activity of interferon in transformed lines. While the MEB-MCH cells required 1000 units of interferon for a 30% growth inhibition, about 3000 units were necessary for a comparable suppression of MEB-SV 40 cells and/or MEB-MSV cells.", "contents": "Antiviral and anticellular effects of interferon on the mouse embryonic cells transformed by viruses and/or chemical carcinogen. The antiviral and anticellular activity of partially purified mouse interferon has been tested in cell lines transformed with Simian Virus 40 (MEB-SV 40), mouse sarcoma virus (Harvey strain) (MEB-MSV), and 20-methylcholanthrene (MEB-MCH), respectively. The transformed lines were derived from C3H mouse embryonic primary cells. It has been shown that the MEB-MSV cells were 10 to 50 times less sensitive to the antiviral effect of interferon than the MEB-SV 40 or MEB-MCH cells. A 30% reduction of the number of treated cells as compared with untreated control cells was taken as basis for comparison of anticellular activity of interferon in transformed lines. While the MEB-MCH cells required 1000 units of interferon for a 30% growth inhibition, about 3000 units were necessary for a comparable suppression of MEB-SV 40 cells and/or MEB-MSV cells."}
{"id": "PMID:230679", "title": "The effect of interferon induction on complement level in rat.", "content": "Relatively high levels of interferon were achieved in rat sera by intracardial inoculation with Sindbis virus followed 15 min later by intraperitoneal application of dimethylsulfoxide. At intervals when interferon titres reached the maximum, the levels of complement were decreased as compared with the control group of rats. Single administration of dimethylsulfoxide did neither induce interferon nor influence the complement levels in sera of rats of the Dobr\u00e1 Voda breed tested. Similar results were obtained with concentrated Newcastle disease virus inoculated intraperitoneally. Of interest is the finding that properdin levels seem to increase at the same time as interferon.", "contents": "The effect of interferon induction on complement level in rat. Relatively high levels of interferon were achieved in rat sera by intracardial inoculation with Sindbis virus followed 15 min later by intraperitoneal application of dimethylsulfoxide. At intervals when interferon titres reached the maximum, the levels of complement were decreased as compared with the control group of rats. Single administration of dimethylsulfoxide did neither induce interferon nor influence the complement levels in sera of rats of the Dobr\u00e1 Voda breed tested. Similar results were obtained with concentrated Newcastle disease virus inoculated intraperitoneally. Of interest is the finding that properdin levels seem to increase at the same time as interferon."}
{"id": "PMID:230684", "title": "Secondary malignant tumors accompanied by primary hepatocellular carcinoma.", "content": "The occurrence of liver cirrhosis and PHC cases were analyzed from the autopsy material of three hospitals. In the course of this work 13,369 autopsy reports were examined. In 339 cases liver cirrhosis was established, the frequency of association with PHC was 19.4% (66 cases). Out of 66 PHC cases 17 (25.6%) were associated with a secondary malignant tumor. This number is 10 times greater than that of other tumors of epithelial origin. It also exceeds the enlarged number of linked secondary tumors as shown in the case of certain lymphoproliferative diseases.", "contents": "Secondary malignant tumors accompanied by primary hepatocellular carcinoma. The occurrence of liver cirrhosis and PHC cases were analyzed from the autopsy material of three hospitals. In the course of this work 13,369 autopsy reports were examined. In 339 cases liver cirrhosis was established, the frequency of association with PHC was 19.4% (66 cases). Out of 66 PHC cases 17 (25.6%) were associated with a secondary malignant tumor. This number is 10 times greater than that of other tumors of epithelial origin. It also exceeds the enlarged number of linked secondary tumors as shown in the case of certain lymphoproliferative diseases."}
{"id": "PMID:230681", "title": "Cytodiagnosis of viral infections in body cavity fluids.", "content": "Pleural and pericardial fluid specimens have been studied in seven patients with diagnosis of viral infection. Intranuclear inclusions, multinucleated giant cells with gelatinous nuclear changes and atypical mesothelial cells were observed. These observations suggest that viral involvement of the mesothelium produces cellular changes which can be detected cytologically in routine Papanicolaou-stained body cavity fluid specimens.", "contents": "Cytodiagnosis of viral infections in body cavity fluids. Pleural and pericardial fluid specimens have been studied in seven patients with diagnosis of viral infection. Intranuclear inclusions, multinucleated giant cells with gelatinous nuclear changes and atypical mesothelial cells were observed. These observations suggest that viral involvement of the mesothelium produces cellular changes which can be detected cytologically in routine Papanicolaou-stained body cavity fluid specimens."}
{"id": "PMID:230685", "title": "Acid secretion and mucosal cyclic nucleotide content of the guinea pig isolated stomach during bethanechol stimulation.", "content": "Acid secretion and mucosal cyclic AMP and cyclic GMP content of guinea pig isolated stomach preparations were measured at various times after stimulation with bethanechol (1.7 X 10(-5) M). Significant increases in acid secretion were observed without changes in cyclic nucleotides. Pre-incubation of the tissues with theophylline (10(-3) M) increased acid secretion and nucleotide content. An additional increase in acid secretion was then obtained with bethanechol in these tissues but without further change in nucleotides. Carbachol (30 micrograms/kg) administered by interperitoneal injection to conscious guinea pigs also failed to change gastric mucosal cyclic nucleotides when the animals were sacrificed 15 min later. These results are discussed in relation to the mechanisms of cholinergic stimulation of gastric acid secretion.", "contents": "Acid secretion and mucosal cyclic nucleotide content of the guinea pig isolated stomach during bethanechol stimulation. Acid secretion and mucosal cyclic AMP and cyclic GMP content of guinea pig isolated stomach preparations were measured at various times after stimulation with bethanechol (1.7 X 10(-5) M). Significant increases in acid secretion were observed without changes in cyclic nucleotides. Pre-incubation of the tissues with theophylline (10(-3) M) increased acid secretion and nucleotide content. An additional increase in acid secretion was then obtained with bethanechol in these tissues but without further change in nucleotides. Carbachol (30 micrograms/kg) administered by interperitoneal injection to conscious guinea pigs also failed to change gastric mucosal cyclic nucleotides when the animals were sacrificed 15 min later. These results are discussed in relation to the mechanisms of cholinergic stimulation of gastric acid secretion."}
{"id": "PMID:230682", "title": "Cytomorphology of carcinoid tumors.", "content": "This report is based on a review and study of carcinoid tumors as seen in smears prepared from exfoliative or aspiration smears. During a period of eight years (1970 to 1978), 236 cytologic specimens were examined from 64 patients treated for carcinoid tumors at Memorial Hospital. Thirty-eight cytologic specimens from 18 patients were interpreted as either suspicious or positive for malignant cells. Tumor cells were identified most often in tracheobronchial specimens, effusions and percutaneous aspirates. A striking similarity in cell morphology was found between exfoliated and aspirated tumor cells. Certain specific or suggestive cytologic features were recognized. The histogenesis of carcinoids and the role of intracytoplasmic neurosecretory granules in the differential diagnosis is discussed together with the clinicopathologic implication of positive cytologic findings.", "contents": "Cytomorphology of carcinoid tumors. This report is based on a review and study of carcinoid tumors as seen in smears prepared from exfoliative or aspiration smears. During a period of eight years (1970 to 1978), 236 cytologic specimens were examined from 64 patients treated for carcinoid tumors at Memorial Hospital. Thirty-eight cytologic specimens from 18 patients were interpreted as either suspicious or positive for malignant cells. Tumor cells were identified most often in tracheobronchial specimens, effusions and percutaneous aspirates. A striking similarity in cell morphology was found between exfoliated and aspirated tumor cells. Certain specific or suggestive cytologic features were recognized. The histogenesis of carcinoids and the role of intracytoplasmic neurosecretory granules in the differential diagnosis is discussed together with the clinicopathologic implication of positive cytologic findings."}
{"id": "PMID:230686", "title": "The energy systems of gastric tissues, their neural, hormonal and pharmacological regulations in order to gastric H+ secretion and ulcerogenesis. (A review of animal experiments and clinical biochemical studies).", "content": "In studies conducted over the last 10 years, the ATP, ADP, AMP concentrations, the adenylate pool (ATP + ADP + AMP), the \"energy charge\" and the cAMP levels were determined:(1) in gastric tissues of pylorus-ligated rats, (2) in gastric and duodenal mucosa and muscular layer (musculature) of human subjects qualified as \"hypacid\", \"normacid\" and \"hyperacid\" on the basis of basal (BAO) and maximal acid output (MAO), (3) in ulcer-bearing and non-ulcerous antral, duodenal and jejunal mucosa and muscular layer of patients with peptic ulcer, including chronic (essential) antral, duodenal ulcer and jejunal ulcer following gastric resection of Billroth II-type. Close analysis of the results centres on: (1) the biochemical background of gastric hypersecretion and of ulcerogenesis in pylorus-ligated rats;(2) the extra- and intracellular feedback system operating between the gastric membrane ATPase and adenylate cyclase systems, under normal and abnormal conditions of the effector organ; (3) questions related to the regulatory mechanisms of functional activity of the effector organ under drug effect; (4) the energy structure of the mucosa and muscular layer of corpus ventriculi, antrum and duodenum in patients considered \"hypacid\", \"normacid\" and \"hyperacid\" on the grounds of the BAO and MAO values; (5) the interrelationships between human gastric H+--K+-dependent ATPase system of gastric corpus mucosa; (6) pharmacological regulation of the ATP--ADcer-free mucosa and musculature of patients with antral, duodenal and jejunal ulcers.", "contents": "The energy systems of gastric tissues, their neural, hormonal and pharmacological regulations in order to gastric H+ secretion and ulcerogenesis. (A review of animal experiments and clinical biochemical studies). In studies conducted over the last 10 years, the ATP, ADP, AMP concentrations, the adenylate pool (ATP + ADP + AMP), the \"energy charge\" and the cAMP levels were determined:(1) in gastric tissues of pylorus-ligated rats, (2) in gastric and duodenal mucosa and muscular layer (musculature) of human subjects qualified as \"hypacid\", \"normacid\" and \"hyperacid\" on the basis of basal (BAO) and maximal acid output (MAO), (3) in ulcer-bearing and non-ulcerous antral, duodenal and jejunal mucosa and muscular layer of patients with peptic ulcer, including chronic (essential) antral, duodenal ulcer and jejunal ulcer following gastric resection of Billroth II-type. Close analysis of the results centres on: (1) the biochemical background of gastric hypersecretion and of ulcerogenesis in pylorus-ligated rats;(2) the extra- and intracellular feedback system operating between the gastric membrane ATPase and adenylate cyclase systems, under normal and abnormal conditions of the effector organ; (3) questions related to the regulatory mechanisms of functional activity of the effector organ under drug effect; (4) the energy structure of the mucosa and muscular layer of corpus ventriculi, antrum and duodenum in patients considered \"hypacid\", \"normacid\" and \"hyperacid\" on the grounds of the BAO and MAO values; (5) the interrelationships between human gastric H+--K+-dependent ATPase system of gastric corpus mucosa; (6) pharmacological regulation of the ATP--ADcer-free mucosa and musculature of patients with antral, duodenal and jejunal ulcers."}
{"id": "PMID:230687", "title": "Optic neuritis: local synthesis in the central nervous system of oligoclonal antibodies to measles, mumps, rubella, and herpes simplex viruses.", "content": "Antibodies to measles, mumps, rubella and herpes simplex type 1 viruses in serum and CSF of 10 patients with acute monosymptomatic optic neuritis were characterized by imprint electro-immunofixation (IEIF). Comparisons of the IEIF antibody patterns in serum and CSF indicated that a local synthesis in the central nervous system of oligoclonal virus antibodies took place in five of the 10 patients. Three of the five patients had a local synthesis of antibody to more than one type of virus. Oligoclonal IgG was detected by agarose electrophoresis of the CSF in four of the five patients with a local synthesis of virus antibodies. There was, however, no association between the locally synthesized antibodies and the oligoclonal CSF IgG, indicating that they account for only a minor fraction of the locally synthesized IgG in these patients. In the fifth patient, distinct fractions of locally synthesized virus-specific oligoclonal Ig were detected by the IEIF method, although the agarose electrophoresis showed a normal pattern of CSF IgG.", "contents": "Optic neuritis: local synthesis in the central nervous system of oligoclonal antibodies to measles, mumps, rubella, and herpes simplex viruses. Antibodies to measles, mumps, rubella and herpes simplex type 1 viruses in serum and CSF of 10 patients with acute monosymptomatic optic neuritis were characterized by imprint electro-immunofixation (IEIF). Comparisons of the IEIF antibody patterns in serum and CSF indicated that a local synthesis in the central nervous system of oligoclonal virus antibodies took place in five of the 10 patients. Three of the five patients had a local synthesis of antibody to more than one type of virus. Oligoclonal IgG was detected by agarose electrophoresis of the CSF in four of the five patients with a local synthesis of virus antibodies. There was, however, no association between the locally synthesized antibodies and the oligoclonal CSF IgG, indicating that they account for only a minor fraction of the locally synthesized IgG in these patients. In the fifth patient, distinct fractions of locally synthesized virus-specific oligoclonal Ig were detected by the IEIF method, although the agarose electrophoresis showed a normal pattern of CSF IgG."}
{"id": "PMID:230683", "title": "Electron microscopy of fine needle aspiration biopsy from a malignant fibrous histiocytoma. Report of a case.", "content": "A case is reported in which electron microscopy was utilized to make a preoperative differential diagnosis of a soft tissue sarcoma on material obtained by fine-needle aspiration biopsy. The value of electron microscopy as an adjunct to cytologic study of such material is pointed out, as is the suitability of aspirated material for electron microscopic examination.", "contents": "Electron microscopy of fine needle aspiration biopsy from a malignant fibrous histiocytoma. Report of a case. A case is reported in which electron microscopy was utilized to make a preoperative differential diagnosis of a soft tissue sarcoma on material obtained by fine-needle aspiration biopsy. The value of electron microscopy as an adjunct to cytologic study of such material is pointed out, as is the suitability of aspirated material for electron microscopic examination."}
{"id": "PMID:230688", "title": "Selective immunodeficiency and malignant lymphoma of the central nervous system. Possible relationship to the Epstein-Barr virus.", "content": "This report presents the findings of a study of a 17-year-old male with a selective immunodeficiency to the Epstein-Barr virus, who died of a malignant lymphoma following clinical infectious mononucleosis. Autopsy findings and immunohistochemical techniques demonstrated a malignant lymphoma with B-lymphocyte characteristics which primarily involved the central nervous system (CNS). The relationship of the Epstein-Barr virus to lymphoproliferation is discussed.", "contents": "Selective immunodeficiency and malignant lymphoma of the central nervous system. Possible relationship to the Epstein-Barr virus. This report presents the findings of a study of a 17-year-old male with a selective immunodeficiency to the Epstein-Barr virus, who died of a malignant lymphoma following clinical infectious mononucleosis. Autopsy findings and immunohistochemical techniques demonstrated a malignant lymphoma with B-lymphocyte characteristics which primarily involved the central nervous system (CNS). The relationship of the Epstein-Barr virus to lymphoproliferation is discussed."}
{"id": "PMID:230689", "title": "Tumorigenic clones of hamster brain cells transformed in vitro by polyoma virus. Ultrastructural and immunohistochemical study.", "content": "The morphological characteristics of three clones of hamster brain cells transformed in vitro by polyoma virus and of the tumors obtained after subcutaneous grafting of these cells in syngenic animals are reported. These clones appeared to be glial in nature by light and electron microscopy. The initial tumors induced by the three clones presented astrocytic features both by electron microscopy and immunohistochemistry. Analysis of the subsequent in vivo passages showed a decrease in cell differentiation, which was accompanied by a decrease in the latency period; after 2 years of serial transplantation, the tumors seemed poorly differentiated gliomas. A control cell line of hamster cerebellar cells evolved similarly.", "contents": "Tumorigenic clones of hamster brain cells transformed in vitro by polyoma virus. Ultrastructural and immunohistochemical study. The morphological characteristics of three clones of hamster brain cells transformed in vitro by polyoma virus and of the tumors obtained after subcutaneous grafting of these cells in syngenic animals are reported. These clones appeared to be glial in nature by light and electron microscopy. The initial tumors induced by the three clones presented astrocytic features both by electron microscopy and immunohistochemistry. Analysis of the subsequent in vivo passages showed a decrease in cell differentiation, which was accompanied by a decrease in the latency period; after 2 years of serial transplantation, the tumors seemed poorly differentiated gliomas. A control cell line of hamster cerebellar cells evolved similarly."}
{"id": "PMID:230690", "title": "Ultrastructural study of medullomyoblastoma.", "content": "A case of cerebellar medullomyoblastoma in a young boy was investigated by electron microscopy. The neuroectodermal component shows the characteristics of a desmoplastic medulloblastoma. The mesodermal component consists of more or less differentiated cross-striated muscle cells. Undifferentiated muscle cells are very similar to proliferated endothelial cells of blood vessels within the muscular component, so that an origin of this component from pluripotential endothelial cells of the vessel wall is suggested. This tumor is considered a malignant teratoid because of the derivation from two blastodermic layers and because of the midline localization in children suggesting a malformative origin.", "contents": "Ultrastructural study of medullomyoblastoma. A case of cerebellar medullomyoblastoma in a young boy was investigated by electron microscopy. The neuroectodermal component shows the characteristics of a desmoplastic medulloblastoma. The mesodermal component consists of more or less differentiated cross-striated muscle cells. Undifferentiated muscle cells are very similar to proliferated endothelial cells of blood vessels within the muscular component, so that an origin of this component from pluripotential endothelial cells of the vessel wall is suggested. This tumor is considered a malignant teratoid because of the derivation from two blastodermic layers and because of the midline localization in children suggesting a malformative origin."}
{"id": "PMID:230691", "title": "Myelin lesions in the rabbit eye model as a bystander effect of herpes simplex and visna virus sensitization.", "content": "Rabbits were immunized with herpes simplex and visna virus in complete Freund's adjuvant. Uv-inactivated herpes virus and the purified visna virus protein p25 injected intraocularly into these rabbits elicited a moderate inflammatory cell infiltration in the epiretinal myelinated nerve fiber bundles accompanied by signs of demyelination. It is therefore apparent that also viral antigen can induce myelin lesions as a so-called \"bystander effect\" of a cell-mediated immune response (bystander demyelination).", "contents": "Myelin lesions in the rabbit eye model as a bystander effect of herpes simplex and visna virus sensitization. Rabbits were immunized with herpes simplex and visna virus in complete Freund's adjuvant. Uv-inactivated herpes virus and the purified visna virus protein p25 injected intraocularly into these rabbits elicited a moderate inflammatory cell infiltration in the epiretinal myelinated nerve fiber bundles accompanied by signs of demyelination. It is therefore apparent that also viral antigen can induce myelin lesions as a so-called \"bystander effect\" of a cell-mediated immune response (bystander demyelination)."}
{"id": "PMID:230692", "title": "The ultrastructural variability of non-specific lipopigments.", "content": "Abnormally structured lipofuscin granules found in various cell types of different conditions not related to the neuronal lipofuscinoses (NCL), emphasize the ultrastructural diversity of non-specific lipofuscin morphologically marked by paracristalline inclusions, pseudo-fingerprint enclosures, and stacks of parallel filaments, all of them embedded in the granular matrix of the lipopigments. Though lipofuscin consisting of the regular granulo-vacuolar ultrastructure was also present in many cells of the same tissues, our findings suggest differences, though of unknown biochemical nature, in lysosomal catabolism resulting in varying lipopigment structures within similar cellular compartments.", "contents": "The ultrastructural variability of non-specific lipopigments. Abnormally structured lipofuscin granules found in various cell types of different conditions not related to the neuronal lipofuscinoses (NCL), emphasize the ultrastructural diversity of non-specific lipofuscin morphologically marked by paracristalline inclusions, pseudo-fingerprint enclosures, and stacks of parallel filaments, all of them embedded in the granular matrix of the lipopigments. Though lipofuscin consisting of the regular granulo-vacuolar ultrastructure was also present in many cells of the same tissues, our findings suggest differences, though of unknown biochemical nature, in lysosomal catabolism resulting in varying lipopigment structures within similar cellular compartments."}
{"id": "PMID:230693", "title": "Effects of three different combinations of ethinyl estradiol and levonorgestrel on plasma lipids and high density lipoproteins.", "content": "Seventy-five menstruating women seeking contraceptive advice were randomly allocated to treatment with combined oral contraceptives containing either ethinyl estradiol 30 micrograms + levonorgestrel 150 micrograms (30/150), ethinyl estradiol 50 micrograms + levonorgestrel 125 micrograms (50/125) or ethinyl estradiol 50 micrograms + levonorgestrel 250 micrograms (50/250). The concentrations of cholesterol, phospholipids, high density lipoprotein (HDL)-cholesterol, HDL-phospholipids and triglycerides were determined prior to treatment and after one, three and six months of medication. Triglycerides increased by 18--42 per cent after one to six months of treatment with 50/125. The HDL-cholesterol and HDL-phospholipids were reduced by 10 per cent during 50/250 medication. No other parameters showed any consistent alteration in any of the treatment groups. Raised triglyceride concentration and/or decreased HDL concentration may increase the risk for cardiovascular disease. It is therefore suggested that in order not to alter the HDL concentration a combined oral contraceptive agent should probably not contain more 19-nortestosterone type of progestogen than corresponding to 125--150 micrograms of levonorgestrel. To avoid a rise of the triglyceride level the weight relation between levonorgestrel and ethinyl estradiol should be about 5:1.", "contents": "Effects of three different combinations of ethinyl estradiol and levonorgestrel on plasma lipids and high density lipoproteins. Seventy-five menstruating women seeking contraceptive advice were randomly allocated to treatment with combined oral contraceptives containing either ethinyl estradiol 30 micrograms + levonorgestrel 150 micrograms (30/150), ethinyl estradiol 50 micrograms + levonorgestrel 125 micrograms (50/125) or ethinyl estradiol 50 micrograms + levonorgestrel 250 micrograms (50/250). The concentrations of cholesterol, phospholipids, high density lipoprotein (HDL)-cholesterol, HDL-phospholipids and triglycerides were determined prior to treatment and after one, three and six months of medication. Triglycerides increased by 18--42 per cent after one to six months of treatment with 50/125. The HDL-cholesterol and HDL-phospholipids were reduced by 10 per cent during 50/250 medication. No other parameters showed any consistent alteration in any of the treatment groups. Raised triglyceride concentration and/or decreased HDL concentration may increase the risk for cardiovascular disease. It is therefore suggested that in order not to alter the HDL concentration a combined oral contraceptive agent should probably not contain more 19-nortestosterone type of progestogen than corresponding to 125--150 micrograms of levonorgestrel. To avoid a rise of the triglyceride level the weight relation between levonorgestrel and ethinyl estradiol should be about 5:1."}
{"id": "PMID:230694", "title": "Treatment of post-menopausal hypercholesterolaemia with estradiol.", "content": "Replacement therapy with estradiol valerate in 29 post-menopausal women reduced low-density lipoprotein (LDL) cholesterol concentrations by 22% and increased high-density lipoprotein (HDL) cholesterol by 21% after 12 months. Apart from a 67% increase of HDL-triglyceride estradiol had only a slight effect on the levels of lipoprotein triglycerides. Post-heparin plasma lipoprotein lipase (LPL) activity was significantly decreased in subjects with normal pre-treatment very-low-density lipoprotein (VLDL) triglyceride levels, and hepatic lipase (HL) activity was significantly decreased in the group as a whole. It is suggested that estradiol replacement therapy should be considered in climacteric women with high LDL-cholesterol or low HDL-cholesterol levels, or both.", "contents": "Treatment of post-menopausal hypercholesterolaemia with estradiol. Replacement therapy with estradiol valerate in 29 post-menopausal women reduced low-density lipoprotein (LDL) cholesterol concentrations by 22% and increased high-density lipoprotein (HDL) cholesterol by 21% after 12 months. Apart from a 67% increase of HDL-triglyceride estradiol had only a slight effect on the levels of lipoprotein triglycerides. Post-heparin plasma lipoprotein lipase (LPL) activity was significantly decreased in subjects with normal pre-treatment very-low-density lipoprotein (VLDL) triglyceride levels, and hepatic lipase (HL) activity was significantly decreased in the group as a whole. It is suggested that estradiol replacement therapy should be considered in climacteric women with high LDL-cholesterol or low HDL-cholesterol levels, or both."}
{"id": "PMID:230695", "title": "Lipid metabolic studies in oophorectomized women. Effects of three different progestogens.", "content": "Ten oophorectomized women (ranging in age from 27 to 45 years, having a mean age of 34.5 years with a standard deviation of 5.3) were given three different progestogens (norgestrel, norethisterone and medroxyprogesterone) in treatment periods of 3 weeks' duration immediately preceded by 3 weeks \"wash out\" periods. Venous blood samples were drawn before and after each treatment period. Free and total cholesterol, triglycerides and phospholipids were determined in the three lipoprotein fractions: Very low density lipoproteins (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL). Individual phosphatides were determined after thin layer chromatography. In addition, the relative fatty acid composition of serum lecithin and cholesterol esters were assessed by gas-liquid-chromatography. Both norethisterone and norgestrel caused a decrease in alpha-lipoprotein cholesterol. The relative fatty acid composition of serum lecithin revealed an increase of biochemical pathway 1 for liver lecithin synthesis on norgestrel and norethisterone but no major changes on medroxyprogesterone. With norgestrel an increase in serum-lysolecithin concomitant with a decrease in lecithin was observed, while the two other progestogens did not induce any significant changes. From the present data it is suggested that the 19-norethisterone derivatives, norethisterone and especially norgestrel, have androgen-like influences on lipid metabolism. Medroxyprogesterone, being a 17-alpha-hydroxyprogesterone, caused less changes and consequently less disturbance of lipid metabolism.", "contents": "Lipid metabolic studies in oophorectomized women. Effects of three different progestogens. Ten oophorectomized women (ranging in age from 27 to 45 years, having a mean age of 34.5 years with a standard deviation of 5.3) were given three different progestogens (norgestrel, norethisterone and medroxyprogesterone) in treatment periods of 3 weeks' duration immediately preceded by 3 weeks \"wash out\" periods. Venous blood samples were drawn before and after each treatment period. Free and total cholesterol, triglycerides and phospholipids were determined in the three lipoprotein fractions: Very low density lipoproteins (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL). Individual phosphatides were determined after thin layer chromatography. In addition, the relative fatty acid composition of serum lecithin and cholesterol esters were assessed by gas-liquid-chromatography. Both norethisterone and norgestrel caused a decrease in alpha-lipoprotein cholesterol. The relative fatty acid composition of serum lecithin revealed an increase of biochemical pathway 1 for liver lecithin synthesis on norgestrel and norethisterone but no major changes on medroxyprogesterone. With norgestrel an increase in serum-lysolecithin concomitant with a decrease in lecithin was observed, while the two other progestogens did not induce any significant changes. From the present data it is suggested that the 19-norethisterone derivatives, norethisterone and especially norgestrel, have androgen-like influences on lipid metabolism. Medroxyprogesterone, being a 17-alpha-hydroxyprogesterone, caused less changes and consequently less disturbance of lipid metabolism."}
{"id": "PMID:230696", "title": "Neutralizing antibodies against herpes simplex virus in maternal and umbilical cord serum.", "content": "Thirteen Japanese with a full term pregnancy were studied to determine maternal and neonatal serum neutralizing antibodies against herpes simplex virus (HSV). The study included 10 healthy persons, 2 with herpes genitalis and one with herpes oralis. We found that the serum neutralizing antibody titers in neonates were almost identical or slightly higher as compared to those in the mother and such findings suggest, that in the neonate, the lack of certain immunological responses may be responsible for generalized herpes simplex virus infection.", "contents": "Neutralizing antibodies against herpes simplex virus in maternal and umbilical cord serum. Thirteen Japanese with a full term pregnancy were studied to determine maternal and neonatal serum neutralizing antibodies against herpes simplex virus (HSV). The study included 10 healthy persons, 2 with herpes genitalis and one with herpes oralis. We found that the serum neutralizing antibody titers in neonates were almost identical or slightly higher as compared to those in the mother and such findings suggest, that in the neonate, the lack of certain immunological responses may be responsible for generalized herpes simplex virus infection."}
{"id": "PMID:230697", "title": "Arteriography and chemotherapy in localized trophoblastic disease, by means of local- (pelvic-) intraarterial infusion.", "content": "In spite of considerable progress in systemic chemotherapy in malignant throphoblastic disease, there remains a small group of patients who fail to respond to this type of therapy. Here the trophoblastic process may be localized by means of an arteriography, and treated by a local, intraarterial infusion of cytotoxic compounds in high concentration. The latter makes possible the treatment of processes localized in essential organs which are hard to remove, as well as in young women wishing to preserve their reproductive capacity. Our experiences is limited to one case of a young woman with chorioadenoma destruens in the uterus, resistant to systemic chemotherapy, yet successfully treated with pelvic, intraarterial infusion of cytotoxics.", "contents": "Arteriography and chemotherapy in localized trophoblastic disease, by means of local- (pelvic-) intraarterial infusion. In spite of considerable progress in systemic chemotherapy in malignant throphoblastic disease, there remains a small group of patients who fail to respond to this type of therapy. Here the trophoblastic process may be localized by means of an arteriography, and treated by a local, intraarterial infusion of cytotoxic compounds in high concentration. The latter makes possible the treatment of processes localized in essential organs which are hard to remove, as well as in young women wishing to preserve their reproductive capacity. Our experiences is limited to one case of a young woman with chorioadenoma destruens in the uterus, resistant to systemic chemotherapy, yet successfully treated with pelvic, intraarterial infusion of cytotoxics."}
{"id": "PMID:230698", "title": "Hyperlipoproteinemia in newborn infants. A study of 1025 families.", "content": "As part of a screening study for the detection of hyperlipoproteinemia in 10,000 newborns, cord serum lipids and lipoproteins were measured in detail in 1025 infants. Elevated cord serum VLDL-LDL-cholesterol could easily be identified by a rapid turbidimetric estimation of cord serum VLDL-LDL. Cord serum VLDL-LDL-cholesterol was found to be significantly higher than normal in premature, asphyxiated and beta-methasone-phenobarbital-ritodrine treated infants. Other obstetric complications, however, were not associated with hyperlipoproteinemia. Furthermore all 2050 parents had their serum cholesterol determined. 3 parents had familial hypercholesterolemia (FH). One child also had FH, though her cord serum total cholesterol and VLDL-LDL-cholesterol were normal. The 2 other children of the 3 FH parents, had normal lipids and lipoproteins both at birth and follow-up.", "contents": "Hyperlipoproteinemia in newborn infants. A study of 1025 families. As part of a screening study for the detection of hyperlipoproteinemia in 10,000 newborns, cord serum lipids and lipoproteins were measured in detail in 1025 infants. Elevated cord serum VLDL-LDL-cholesterol could easily be identified by a rapid turbidimetric estimation of cord serum VLDL-LDL. Cord serum VLDL-LDL-cholesterol was found to be significantly higher than normal in premature, asphyxiated and beta-methasone-phenobarbital-ritodrine treated infants. Other obstetric complications, however, were not associated with hyperlipoproteinemia. Furthermore all 2050 parents had their serum cholesterol determined. 3 parents had familial hypercholesterolemia (FH). One child also had FH, though her cord serum total cholesterol and VLDL-LDL-cholesterol were normal. The 2 other children of the 3 FH parents, had normal lipids and lipoproteins both at birth and follow-up."}
{"id": "PMID:230700", "title": "Local articular amyloid deposition in pyrophosphate arthritis. Histological aspects.", "content": "A material of 15 cases of histologically examined pyrophosphate arthritis (hip-joint: 7 cases, knee joint: 8 cases) is presented. Amyloid deposits were found in 14 cases and chondromatosis in the subsynovial connective tissue of all the cases. The significance of this high, not previously reported, coincidence is discussed, together with various pathogenetic possibilities, as related to the theories of the genesis of amyloid substance.", "contents": "Local articular amyloid deposition in pyrophosphate arthritis. Histological aspects. A material of 15 cases of histologically examined pyrophosphate arthritis (hip-joint: 7 cases, knee joint: 8 cases) is presented. Amyloid deposits were found in 14 cases and chondromatosis in the subsynovial connective tissue of all the cases. The significance of this high, not previously reported, coincidence is discussed, together with various pathogenetic possibilities, as related to the theories of the genesis of amyloid substance."}
{"id": "PMID:230701", "title": "Extreme duct papillomatosis of the juvenile breast.", "content": "Three cases of peculiar and very severe ductal papillomatosis of the breast are reported. This ductal papillomatosis was unusual, both in its histological architecture and in occurring in juveniles, viz. girls aged 11, 14, and 17 years. In two of the patients breast cancer was diagnosed 27 and 11 years later. In one of them the ductal papillomatosis must be presumed to have been precancerosis, while in the other patient there was possibly from the outset an unusually papilliferous, intraductal carcinoma of low malignancy.", "contents": "Extreme duct papillomatosis of the juvenile breast. Three cases of peculiar and very severe ductal papillomatosis of the breast are reported. This ductal papillomatosis was unusual, both in its histological architecture and in occurring in juveniles, viz. girls aged 11, 14, and 17 years. In two of the patients breast cancer was diagnosed 27 and 11 years later. In one of them the ductal papillomatosis must be presumed to have been precancerosis, while in the other patient there was possibly from the outset an unusually papilliferous, intraductal carcinoma of low malignancy."}
{"id": "PMID:230702", "title": "The effect of transmural field stimulation on the serotonin content in rat duodenal enterochromaffin cells--in vitro.", "content": "The effect of transmural field stimulation (TFS)--in vitro--on the sertonin (5-HT) content in enterochromafffin cells (EC) in rat duodenum was studied with a cytofluorimetric method. TFS caused a significant 25% decrease of 5-HT in EC. The presence of tetrodotoxin or d,1-propranolol in the stimulation bath antagonized the effect of TFS. In biopsies from rats pretreated with 6-OH-dopamine TFS had no effect of the 5-HT content in EC. The results of the present study strongly suggest, that the TFS induced decrease in 5-HT content is due to a direct neural, probably beta-adrenoceptor mediated, influence on the EC.", "contents": "The effect of transmural field stimulation on the serotonin content in rat duodenal enterochromaffin cells--in vitro. The effect of transmural field stimulation (TFS)--in vitro--on the sertonin (5-HT) content in enterochromafffin cells (EC) in rat duodenum was studied with a cytofluorimetric method. TFS caused a significant 25% decrease of 5-HT in EC. The presence of tetrodotoxin or d,1-propranolol in the stimulation bath antagonized the effect of TFS. In biopsies from rats pretreated with 6-OH-dopamine TFS had no effect of the 5-HT content in EC. The results of the present study strongly suggest, that the TFS induced decrease in 5-HT content is due to a direct neural, probably beta-adrenoceptor mediated, influence on the EC."}
{"id": "PMID:230703", "title": "Transcatheter arterial embolisation in nasopharyngeal angiofibroma.", "content": "Transcatheter arterial embolisation using gelfoam particles has been used in 4 young male patients with nasopharyngeal angiofibroma. The procedure proved to be extremely useful preoperatively in controlling and limiting profuse bleeding during surgery, allowing total excision of the tumor.", "contents": "Transcatheter arterial embolisation in nasopharyngeal angiofibroma. Transcatheter arterial embolisation using gelfoam particles has been used in 4 young male patients with nasopharyngeal angiofibroma. The procedure proved to be extremely useful preoperatively in controlling and limiting profuse bleeding during surgery, allowing total excision of the tumor."}
{"id": "PMID:230704", "title": "Contrast enhancement with time in gliomas. Stereotactic computer tomography following contrast medium infusion.", "content": "Dynamic enhancement of astrocytomas has been investigated with CT following infusion of contrast medium. The areas of measurement corresponded with obtained stereotactic biopsies. The resulting types of enhancement are discussed in terms of a 3-compartment model. Great differences exist in the degree of enhancement of astrocytomas of grade I to II and those of grade III to IV. In the latter tumours a dynamic response appears to occur, distinctly different from that in infarctions.", "contents": "Contrast enhancement with time in gliomas. Stereotactic computer tomography following contrast medium infusion. Dynamic enhancement of astrocytomas has been investigated with CT following infusion of contrast medium. The areas of measurement corresponded with obtained stereotactic biopsies. The resulting types of enhancement are discussed in terms of a 3-compartment model. Great differences exist in the degree of enhancement of astrocytomas of grade I to II and those of grade III to IV. In the latter tumours a dynamic response appears to occur, distinctly different from that in infarctions."}
{"id": "PMID:230705", "title": "Primary brain tumour presenting as spontaneous intracerebral haemorrhage.", "content": "In an autopsy series of 430 spontaneous intracerebral haematomas 44 cases, or 10.2 percent, were caused by a proved neoplasm, including 21 anaplastic gliomas, 17 metastases, 2 oligodendrogliomas, 2 malignant lymphomas, and one meningioma. These instances of massive bleeding into brain tumour represented 2.4 percent of about 1,800 primary and secondary cerebral neoplasms proved by necropsy. In only four of the patients with primary brain tumours (two glioblastomas, one oligodendroglioma invading the leptomeninges, and one primary malignant lymphoma), three of them with a history of arterial hypertension, were the presenting symptoms these of a spontaneous intracerebral haemorrhage, and the tumour itself was not diagnosed until surgery or necropsy. One patient with acute haemorrhage into a glioblastoma of the basal ganglia showed a rapidly lethal course, while the others demonstrated one or more episodes before the onset of the acute fatal illness and a prolonged period from the time of the bleed until death. The clinical features and the pathogenesis of spontaneous haemorrhage into cerebral neoplasms are briefly reviewed.", "contents": "Primary brain tumour presenting as spontaneous intracerebral haemorrhage. In an autopsy series of 430 spontaneous intracerebral haematomas 44 cases, or 10.2 percent, were caused by a proved neoplasm, including 21 anaplastic gliomas, 17 metastases, 2 oligodendrogliomas, 2 malignant lymphomas, and one meningioma. These instances of massive bleeding into brain tumour represented 2.4 percent of about 1,800 primary and secondary cerebral neoplasms proved by necropsy. In only four of the patients with primary brain tumours (two glioblastomas, one oligodendroglioma invading the leptomeninges, and one primary malignant lymphoma), three of them with a history of arterial hypertension, were the presenting symptoms these of a spontaneous intracerebral haemorrhage, and the tumour itself was not diagnosed until surgery or necropsy. One patient with acute haemorrhage into a glioblastoma of the basal ganglia showed a rapidly lethal course, while the others demonstrated one or more episodes before the onset of the acute fatal illness and a prolonged period from the time of the bleed until death. The clinical features and the pathogenesis of spontaneous haemorrhage into cerebral neoplasms are briefly reviewed."}
{"id": "PMID:230729", "title": "Prostaglandins and fibroblast functions in vitro.", "content": "Secondary embryonic mouse fibroblasts synthesise mainly E-type PG. The formation of PGF2 alpha is about 10 times lower. No PGI2 formation was observed. Secondary embryonic mouse fibroblasts possess an adenylate cyclase which is stimulated by E-type PGs, but little by PGF2 alpha or PGI2. PGE1-induced stimulation of cAMP levels is dose-dependently linked to an increase in biosynthetic activity of the cells, visible in increased GAG biosynthesis and PG formation. cAMP-dependent enhancement of GAG biosynthesis does not alter the carbohydrate spectrum of the secreted GAG, indicating that only the amount, but not the quality of the secreted GAG is affected by PGE1 or cAMP. Steroidal as well as non-steroidal antirheumatic agents can affect either basal or PGE1 stimulated cAMP levels or other components of the adenylate cyclase system independent of their inhibitory action on PG formation. These effects are always reflected in a decrease or increase of GAG biosynthesis. PGE1-induced stimulation of cAMP levels is related to an inhibition of fibroblast proliferation. Reduction of endogenous PG formation for prolonged periods does not result in a prolonged decrease of intracellular cAMP followed by a decrease in GAG biosynthesis or an increase in proliferation. The initial effect of reduced endogenous PG formation is compensated for by an increased sensitivity of the cells to PG's, resulting in maintenance of basal cAMP levels and an increased sensitivity to exogenous PGE1. These effects on cAMP levels are also reflected in GAG biosynthesis and proliferative activity of the cells.", "contents": "Prostaglandins and fibroblast functions in vitro. Secondary embryonic mouse fibroblasts synthesise mainly E-type PG. The formation of PGF2 alpha is about 10 times lower. No PGI2 formation was observed. Secondary embryonic mouse fibroblasts possess an adenylate cyclase which is stimulated by E-type PGs, but little by PGF2 alpha or PGI2. PGE1-induced stimulation of cAMP levels is dose-dependently linked to an increase in biosynthetic activity of the cells, visible in increased GAG biosynthesis and PG formation. cAMP-dependent enhancement of GAG biosynthesis does not alter the carbohydrate spectrum of the secreted GAG, indicating that only the amount, but not the quality of the secreted GAG is affected by PGE1 or cAMP. Steroidal as well as non-steroidal antirheumatic agents can affect either basal or PGE1 stimulated cAMP levels or other components of the adenylate cyclase system independent of their inhibitory action on PG formation. These effects are always reflected in a decrease or increase of GAG biosynthesis. PGE1-induced stimulation of cAMP levels is related to an inhibition of fibroblast proliferation. Reduction of endogenous PG formation for prolonged periods does not result in a prolonged decrease of intracellular cAMP followed by a decrease in GAG biosynthesis or an increase in proliferation. The initial effect of reduced endogenous PG formation is compensated for by an increased sensitivity of the cells to PG's, resulting in maintenance of basal cAMP levels and an increased sensitivity to exogenous PGE1. These effects on cAMP levels are also reflected in GAG biosynthesis and proliferative activity of the cells."}
{"id": "PMID:230731", "title": "Distribution and further studies on the activity of prostaglandin E in chronic granulomatous inflammation.", "content": "Pre-formed granulomata, induced by cannulated, carrageenin-soaked, subdermal sponge implants, were used to further analyse the effects of exogenous PGE and the involvement of endogenous PGE in this model of chronic inflammatory tissue changes in rats. Experiments with 14C-PGE2 indicated that administration of PGE into the sponge creates a kinetic situation likely to imitate, but superimposed upon, the continuous discharge of endogenous PGE in the granuloma. The granuloma-reducing, anti-flammatory effect of PGE can be mimicked by dibutyryl cyclic-AMP, phosphodiesterase inhibitors and indomethacin. Most probably these compounds, in common with PGE, exert their anti-granuloma action through elevation of intracellular cyclic-AMP (in macrophages and/or fibroblasts). The anti-granuloma action is not necessarily associated with a reduction in the endogenous PGE-level and vice versa. The involvement of endogenous PGE in the tissue events of granulomatous inflammation is conjectural as yet.", "contents": "Distribution and further studies on the activity of prostaglandin E in chronic granulomatous inflammation. Pre-formed granulomata, induced by cannulated, carrageenin-soaked, subdermal sponge implants, were used to further analyse the effects of exogenous PGE and the involvement of endogenous PGE in this model of chronic inflammatory tissue changes in rats. Experiments with 14C-PGE2 indicated that administration of PGE into the sponge creates a kinetic situation likely to imitate, but superimposed upon, the continuous discharge of endogenous PGE in the granuloma. The granuloma-reducing, anti-flammatory effect of PGE can be mimicked by dibutyryl cyclic-AMP, phosphodiesterase inhibitors and indomethacin. Most probably these compounds, in common with PGE, exert their anti-granuloma action through elevation of intracellular cyclic-AMP (in macrophages and/or fibroblasts). The anti-granuloma action is not necessarily associated with a reduction in the endogenous PGE-level and vice versa. The involvement of endogenous PGE in the tissue events of granulomatous inflammation is conjectural as yet."}
{"id": "PMID:230738", "title": "A new method for the generation of standard atmospheres of organo isocyanates.", "content": "A new and versatile method for the generation of standard atmospheres of several organo isocyanates based on permeation technique has been developed. Several membranes were screened for integrity, compatibility and permeability of these isocyanates. Silicone membrane was found to be the best membrane for the construction of permeation devices. Two types of permeation are described: liquid phase and gas phase. The liquid phase permeation tubes are recommended for generation of high concentrations (ppm) and gas phase permeation is preferred for generation of atmospheres with low concentrations (ppb). Several simple designs for construction of permeation devices are described. The permeation of isocynates were evaluated gravimetrically and were shown to be constant, provided the temperature and the flow rate of air over the permeation tube are maintained constant.", "contents": "A new method for the generation of standard atmospheres of organo isocyanates. A new and versatile method for the generation of standard atmospheres of several organo isocyanates based on permeation technique has been developed. Several membranes were screened for integrity, compatibility and permeability of these isocyanates. Silicone membrane was found to be the best membrane for the construction of permeation devices. Two types of permeation are described: liquid phase and gas phase. The liquid phase permeation tubes are recommended for generation of high concentrations (ppm) and gas phase permeation is preferred for generation of atmospheres with low concentrations (ppb). Several simple designs for construction of permeation devices are described. The permeation of isocynates were evaluated gravimetrically and were shown to be constant, provided the temperature and the flow rate of air over the permeation tube are maintained constant."}
{"id": "PMID:230739", "title": "Age-related neurocytotropism of mouse cytomegalovirus in explanted trigeminal ganglions.", "content": "Human cytomegalovirus (CMV) causes severe congenital neurologic disease; adult neural infection is associated with transient cranial nerve palsies. In our experimental model, mouse CMV (MCMV) infects neurons and Schwann and satellite cells of cranial nerve ganglions. To study the fate of MCMV in nerve tissue, we explanted trigeminal ganglions from newborn, suckling, and weanling mice, 3 to 36 days after intracranial inoculation. Negative explants were co-cultivated with mouse embryo tissue culture (METC) to test for latency. MCMV, identified by electron microscopy, replicated in fibroblasts, Schwann cells, and/or satellite cells and neurons of trigeminal explants from newborn and suckling, but not weanling, mice. No latent virus was detected by our methods. The age differences in viral replication may be due to the age-dependent intrinsic cellular mechanisms and host inflammatory and immunologic response. Though neurons are infected, they remain relatively resistant to CMV replication.", "contents": "Age-related neurocytotropism of mouse cytomegalovirus in explanted trigeminal ganglions. Human cytomegalovirus (CMV) causes severe congenital neurologic disease; adult neural infection is associated with transient cranial nerve palsies. In our experimental model, mouse CMV (MCMV) infects neurons and Schwann and satellite cells of cranial nerve ganglions. To study the fate of MCMV in nerve tissue, we explanted trigeminal ganglions from newborn, suckling, and weanling mice, 3 to 36 days after intracranial inoculation. Negative explants were co-cultivated with mouse embryo tissue culture (METC) to test for latency. MCMV, identified by electron microscopy, replicated in fibroblasts, Schwann cells, and/or satellite cells and neurons of trigeminal explants from newborn and suckling, but not weanling, mice. No latent virus was detected by our methods. The age differences in viral replication may be due to the age-dependent intrinsic cellular mechanisms and host inflammatory and immunologic response. Though neurons are infected, they remain relatively resistant to CMV replication."}
{"id": "PMID:230736", "title": "Recovery of pituitary-adrenal axis after withdrawal or reduction of systemic corticosteroids in patients with bronchial asthma.", "content": "In 36 patients with bronchial asthma a new inhalable corticosteroid (Fluocortin-butyl-ester) was administered to reduce systemic steroids and especially to study the recovery of pituitary-adrenal function. On the basis of the present results, it can be said that patients with the least degree of emphysema and obstruction and with good coughing dynamics and productive expectoration are most suitable for therapy with inhalable corticosteroids. If the systemic steroid reduction is adequate, the recovery phase of the pituitary-adrenocortical system begins after about 5 months and the response to ACTH appraoches normal values after about 8-9 months. About 4 mg prednisolone-equivalent per day can be assumed to be the systemically effective limiting dose. The reducibility as a percentage of the initial dose-regardless of its absolute value- and the maintenance dose achieved also appear to be of equal importance for the recovery of the functional reserve of the pituitary-adrenocortical system. No relationship to the duration of the disease and the initial steroid dose could be demonstrated. The clinical picture of the corticosteroid withdrawal syndrome is dependent on endogenous cortisol synthesis. The symptoms disappear spontaneously with increasing synthesis.", "contents": "Recovery of pituitary-adrenal axis after withdrawal or reduction of systemic corticosteroids in patients with bronchial asthma. In 36 patients with bronchial asthma a new inhalable corticosteroid (Fluocortin-butyl-ester) was administered to reduce systemic steroids and especially to study the recovery of pituitary-adrenal function. On the basis of the present results, it can be said that patients with the least degree of emphysema and obstruction and with good coughing dynamics and productive expectoration are most suitable for therapy with inhalable corticosteroids. If the systemic steroid reduction is adequate, the recovery phase of the pituitary-adrenocortical system begins after about 5 months and the response to ACTH appraoches normal values after about 8-9 months. About 4 mg prednisolone-equivalent per day can be assumed to be the systemically effective limiting dose. The reducibility as a percentage of the initial dose-regardless of its absolute value- and the maintenance dose achieved also appear to be of equal importance for the recovery of the functional reserve of the pituitary-adrenocortical system. No relationship to the duration of the disease and the initial steroid dose could be demonstrated. The clinical picture of the corticosteroid withdrawal syndrome is dependent on endogenous cortisol synthesis. The symptoms disappear spontaneously with increasing synthesis."}
{"id": "PMID:230740", "title": "Humoral inhibitors of the immune response in uremia. II. Further characterization of an immunosuppressive factor in uremic serum.", "content": "The serum of Lewis rats with chronic renal insufficiency (induced by subtotal nephrectomy) contains a nondialyzable inhibitor of the mixed lymphocyte reaction. Fractionation of uremic serum by gel filtration on Sephadex G-200 shows that the inhibitory activity elutes with an apparent molecular weight of greater than 200,000 daltons. To establish the possible relationship of the uremic inhibitor to known immunosuppressive components of normal serum, uremic serum was further fractionated on a DEAE cellulose column. The inhibitory activity elutes in 10 mM sodium phosphate at pH 8.0. This fraction contains both alpha-macroglobulin and IgG. The inhibitory activity of this fraction is completely inactivated by treatment with 2-mercaptoethanol, indicating that the inhibitor is a protein. The inhibitory activity is partially inactivated by periodate treatment, suggesting that it may be a glycoprotein. To determine whether or not the inhibitory factor is an immunoregulatory alpha-macroglobulin, or an immune complex, the uremic serum was fractionated by affinity chromatography procedures, which do not induce artifactual inhibitory properties in control serum. The alpha-macroglobulin was removed by affinity chromatography on a column of Con A-Sepharose; its removal had no effect on the inhibitory activity of serum in the mixed lymphocyte reaction. To examine the possibility that immune complexes may be the uremic inhibitor, the serum was fractionated by affinity chromatography on Protein A-Sepharose or by adsorption to a suspension of Staphylococcus aureus, cowan I. Neither of the two latter procedures had any effect on the inhibitory activity of uremic serum. So far all of our findings indicate that the immunosuppressive factor of uremic serum is distinct from two major immunoregulatory factors, alpha-macroglobulin and immune complexes.", "contents": "Humoral inhibitors of the immune response in uremia. II. Further characterization of an immunosuppressive factor in uremic serum. The serum of Lewis rats with chronic renal insufficiency (induced by subtotal nephrectomy) contains a nondialyzable inhibitor of the mixed lymphocyte reaction. Fractionation of uremic serum by gel filtration on Sephadex G-200 shows that the inhibitory activity elutes with an apparent molecular weight of greater than 200,000 daltons. To establish the possible relationship of the uremic inhibitor to known immunosuppressive components of normal serum, uremic serum was further fractionated on a DEAE cellulose column. The inhibitory activity elutes in 10 mM sodium phosphate at pH 8.0. This fraction contains both alpha-macroglobulin and IgG. The inhibitory activity of this fraction is completely inactivated by treatment with 2-mercaptoethanol, indicating that the inhibitor is a protein. The inhibitory activity is partially inactivated by periodate treatment, suggesting that it may be a glycoprotein. To determine whether or not the inhibitory factor is an immunoregulatory alpha-macroglobulin, or an immune complex, the uremic serum was fractionated by affinity chromatography procedures, which do not induce artifactual inhibitory properties in control serum. The alpha-macroglobulin was removed by affinity chromatography on a column of Con A-Sepharose; its removal had no effect on the inhibitory activity of serum in the mixed lymphocyte reaction. To examine the possibility that immune complexes may be the uremic inhibitor, the serum was fractionated by affinity chromatography on Protein A-Sepharose or by adsorption to a suspension of Staphylococcus aureus, cowan I. Neither of the two latter procedures had any effect on the inhibitory activity of uremic serum. So far all of our findings indicate that the immunosuppressive factor of uremic serum is distinct from two major immunoregulatory factors, alpha-macroglobulin and immune complexes."}
{"id": "PMID:230737", "title": "Stimulation of cyclic AMP phosphodiesterase activity by the heated supernatant fraction of canine tracheal smooth muscle.", "content": "The cAMP-hydrolyzing activity (phosphodiesterase) in the supernatant fraction of canine tracheal smooth muscle was approximately doubled by addition of more concentrated, heat-treated tissue extract. The activation was eliminated by EDTA, but addition of calcium produced no greater activation than addition of heated extract alone. It appears that canine tracheal smooth muscle phosphodiesterase can be activated by a heat-stable, calcium-dependent factor.", "contents": "Stimulation of cyclic AMP phosphodiesterase activity by the heated supernatant fraction of canine tracheal smooth muscle. The cAMP-hydrolyzing activity (phosphodiesterase) in the supernatant fraction of canine tracheal smooth muscle was approximately doubled by addition of more concentrated, heat-treated tissue extract. The activation was eliminated by EDTA, but addition of calcium produced no greater activation than addition of heated extract alone. It appears that canine tracheal smooth muscle phosphodiesterase can be activated by a heat-stable, calcium-dependent factor."}
{"id": "PMID:230741", "title": "The effects of ACTH on lung maturation in fetal lambs.", "content": "The ability of adrenocorticotrophic hormone (ACTH) to induce lung maturation was evaluated in fetal lambs. One member of 14 twin pairs between 114 and 138 days of gestation was infused intravenously with 0.5 mg ACTH over 5 days. The lungs of treated versus control lambs were judged more mature by morphologic criteria by the use of light and electron microscopy and by biochemical criteria by the use of lamellar-body-rich cell fractions. None of 5 premature lambs treated with ACTH and allowed to breathe showed evidence of hyaline membrane disease, while 3 untreated control lambs showed typical hyaline membranes.", "contents": "The effects of ACTH on lung maturation in fetal lambs. The ability of adrenocorticotrophic hormone (ACTH) to induce lung maturation was evaluated in fetal lambs. One member of 14 twin pairs between 114 and 138 days of gestation was infused intravenously with 0.5 mg ACTH over 5 days. The lungs of treated versus control lambs were judged more mature by morphologic criteria by the use of light and electron microscopy and by biochemical criteria by the use of lamellar-body-rich cell fractions. None of 5 premature lambs treated with ACTH and allowed to breathe showed evidence of hyaline membrane disease, while 3 untreated control lambs showed typical hyaline membranes."}
{"id": "PMID:230742", "title": "Maxillofacial synovial sarcoma. Light- and electron-microscopic study of two cases.", "content": "The light microscopy and ultrastructural features of two maxillofacial synovial sarcomas are presented. By light microscopy, one of the tumors revealed the typical biphasic pattern while the other was predominantly fibrosarcomatous. Ultrastructurally, both cases revealed a biphasic pattern. Epithelial-like cells displayed abundant mitochondria, Golgi profiles, electron-dense bodies, cytolysosomes, and thin filaments. Stromal cells were spindle-shaped and provided with smaller cytoplasm and scant organelles, mainly consisting of profiles of rough endoplasmic retuculum, mitochondria, and free ribosomes. Pseudoglandular spaces lined by cuboidal to flattened epithelial-like cells with apical microvilli were numerous. Basal lamina and intercellular junctions were prominent in one case, but sparse in the other. The most undifferentiated tumor revealed many intercellular clefts containing filopodia among the epithelial-like cells; occasional intracyltoplasmic lumina were also present. These findings are somewhat similar to those reported in normal and nonneoplastic diseases of the synovium. However, the location of the tumors in areas normally devoid of synovium suggests one more that they might arise from nonspecialized primitive mesenchyme.", "contents": "Maxillofacial synovial sarcoma. Light- and electron-microscopic study of two cases. The light microscopy and ultrastructural features of two maxillofacial synovial sarcomas are presented. By light microscopy, one of the tumors revealed the typical biphasic pattern while the other was predominantly fibrosarcomatous. Ultrastructurally, both cases revealed a biphasic pattern. Epithelial-like cells displayed abundant mitochondria, Golgi profiles, electron-dense bodies, cytolysosomes, and thin filaments. Stromal cells were spindle-shaped and provided with smaller cytoplasm and scant organelles, mainly consisting of profiles of rough endoplasmic retuculum, mitochondria, and free ribosomes. Pseudoglandular spaces lined by cuboidal to flattened epithelial-like cells with apical microvilli were numerous. Basal lamina and intercellular junctions were prominent in one case, but sparse in the other. The most undifferentiated tumor revealed many intercellular clefts containing filopodia among the epithelial-like cells; occasional intracyltoplasmic lumina were also present. These findings are somewhat similar to those reported in normal and nonneoplastic diseases of the synovium. However, the location of the tumors in areas normally devoid of synovium suggests one more that they might arise from nonspecialized primitive mesenchyme."}
{"id": "PMID:230743", "title": "Benign histiocytic tumor of lung. A light- and electron-microscopic study.", "content": "We describe an unusual benign pulmonary neoplasm which was composed entirely of histiocytes and a few chronic inflammatory cells and which posed difficult diagnostic problems. The differential diagnosis is discussed, and the usefulness of electron microscopy in interpreting unusual pulmonary tumors is emphasized.", "contents": "Benign histiocytic tumor of lung. A light- and electron-microscopic study. We describe an unusual benign pulmonary neoplasm which was composed entirely of histiocytes and a few chronic inflammatory cells and which posed difficult diagnostic problems. The differential diagnosis is discussed, and the usefulness of electron microscopy in interpreting unusual pulmonary tumors is emphasized."}
{"id": "PMID:230756", "title": "Toxicologic assessments of a commercial polybrominated biphenyl mixture in the rat.", "content": "A polybrominated biphenyl fire retardant (Firemaster FF-1) was responsible for the widespread environmental contamination and animal losses in Michigan during 1973 and 1974. In Fischer 344/N rats orally given 30,100,300, and 1,000 mg/kg (5 days/week, 22 total doses) for 4.5 weeks and observed for 90 days after the start of treatment, the LD50 was determined to be 65 mg/kg/day (total 1.43 g/kg) for the female rat and 149 mg/kg/day (total 3.28 g/kg) for the male. All female rats given the dosage of 100 mg/kg/day (22 doses, total 2.20 g/kg) died between 41 and 53 days after the start of treatment, whereas 38% of the males died between 50 and 73 days. Pathologic changes in treated rats were large liver, accentuation of the hepatic lobular markings, and atrophy of thymus and spleen. Microscopically, hepatic changes were characterized by congestion, fatty metamorphosis, and multifocal liquefactive necrosis. Male rats given 100 mg/kg/day and dying after 90 days had subacute to chronic hepatitis with marked focal proliferation of bile ducts. Exposure to Firemaster FF-1 may produce atypical liver nodules in the rat as early as 6 months after they were first given the preparation. Marked hepatotoxic effect persisted in surviving rats when examined after 6 months.", "contents": "Toxicologic assessments of a commercial polybrominated biphenyl mixture in the rat. A polybrominated biphenyl fire retardant (Firemaster FF-1) was responsible for the widespread environmental contamination and animal losses in Michigan during 1973 and 1974. In Fischer 344/N rats orally given 30,100,300, and 1,000 mg/kg (5 days/week, 22 total doses) for 4.5 weeks and observed for 90 days after the start of treatment, the LD50 was determined to be 65 mg/kg/day (total 1.43 g/kg) for the female rat and 149 mg/kg/day (total 3.28 g/kg) for the male. All female rats given the dosage of 100 mg/kg/day (22 doses, total 2.20 g/kg) died between 41 and 53 days after the start of treatment, whereas 38% of the males died between 50 and 73 days. Pathologic changes in treated rats were large liver, accentuation of the hepatic lobular markings, and atrophy of thymus and spleen. Microscopically, hepatic changes were characterized by congestion, fatty metamorphosis, and multifocal liquefactive necrosis. Male rats given 100 mg/kg/day and dying after 90 days had subacute to chronic hepatitis with marked focal proliferation of bile ducts. Exposure to Firemaster FF-1 may produce atypical liver nodules in the rat as early as 6 months after they were first given the preparation. Marked hepatotoxic effect persisted in surviving rats when examined after 6 months."}
{"id": "PMID:230757", "title": "Coronaviral enteritis of young calves: virologic and pathologic findings in naturally occurring infections.", "content": "Coronavirus was detected in 113 (16.4%) of 689 calf enteric disease accessions received at the South Dakota Animal Disease Research and Diagnostic Laboratory from Mar 1, 1975 to Oct 31, 1976. During this period, modified live coronaviral vaccine was not in common use in this area. The virus was detected by negative stain electron microscopy of feces and intestinal contents and by fluorescent antibody examination of intestine and colon sections. Calves with coronaviral enteritis ranged in age from 1 day to 3 months, with most cases occurring between 1 and 7 days. At necropsy, a green, mucoid fecal cast was commonly seen in the colon. Histopathologic examination revealed necrotizing enterocolitis.", "contents": "Coronaviral enteritis of young calves: virologic and pathologic findings in naturally occurring infections. Coronavirus was detected in 113 (16.4%) of 689 calf enteric disease accessions received at the South Dakota Animal Disease Research and Diagnostic Laboratory from Mar 1, 1975 to Oct 31, 1976. During this period, modified live coronaviral vaccine was not in common use in this area. The virus was detected by negative stain electron microscopy of feces and intestinal contents and by fluorescent antibody examination of intestine and colon sections. Calves with coronaviral enteritis ranged in age from 1 day to 3 months, with most cases occurring between 1 and 7 days. At necropsy, a green, mucoid fecal cast was commonly seen in the colon. Histopathologic examination revealed necrotizing enterocolitis."}
{"id": "PMID:230758", "title": "Feline infectious peritonitis: a worldwide serosurvey.", "content": "Feline sera from 13 countries were assayed for coronavirus antibody, using a heterologous indirect immunofluorescence test. Significantly higher percentages of antibody carriers were obtained during testing randomly collected sera from mature males (greater than 1 year old) than in testing females of the same age. Antibodies were infrequently found in immature cats (less than 6 months old); at 1 year of age or older, a plateau was reached and little change in the percentage of seroconverted animals was observed. Differences were not detected between purebred cats vs mixed-breed cats or household vs stray cats. In animals showing clinical signs of feline infection peritonitis (FIP), antibodies were encountered with higher frequency than in clinically healthy cats. Significant differences in antibody incidence were found between countries, with a range between less than 10% and greater than 50% of seropositive individuals. Antibodies were detected in sera from an isolated cat population (Marion Island) and from wild-caught cheetahs (Acinonyx jubatus). The antibody specificity for FIP virus was confirmed by neutralization tests. The antibody pattern in randomly collected solitary cats, in catteries, and cats with clinical FIP showed characteristic differences in titer and incidence. The implications of these results for the epizootiology of FIP are discussed.", "contents": "Feline infectious peritonitis: a worldwide serosurvey. Feline sera from 13 countries were assayed for coronavirus antibody, using a heterologous indirect immunofluorescence test. Significantly higher percentages of antibody carriers were obtained during testing randomly collected sera from mature males (greater than 1 year old) than in testing females of the same age. Antibodies were infrequently found in immature cats (less than 6 months old); at 1 year of age or older, a plateau was reached and little change in the percentage of seroconverted animals was observed. Differences were not detected between purebred cats vs mixed-breed cats or household vs stray cats. In animals showing clinical signs of feline infection peritonitis (FIP), antibodies were encountered with higher frequency than in clinically healthy cats. Significant differences in antibody incidence were found between countries, with a range between less than 10% and greater than 50% of seropositive individuals. Antibodies were detected in sera from an isolated cat population (Marion Island) and from wild-caught cheetahs (Acinonyx jubatus). The antibody specificity for FIP virus was confirmed by neutralization tests. The antibody pattern in randomly collected solitary cats, in catteries, and cats with clinical FIP showed characteristic differences in titer and incidence. The implications of these results for the epizootiology of FIP are discussed."}
{"id": "PMID:230760", "title": "Rotavirus antibody assays on monkey sera: a comparison of enzyme immunoassay with neutralization and complement-fixation tests.", "content": "An enzyme immunoassay (EIA) for the detection of rotaviral antibodies was developed, using a purified, cell culture-grown SA 11 viral antigen and alkaline phosphatase as an enzyme label. This technique was evaluated by comparative testing with tube neutralization and complement-fixation assays on a collection of simian sera. There was close correlation between positive and negative results obtained by EIA and by neutralization. The EIA was as easy to perform as complement fixation testing, but showed greater sensitivity and fewer nonspecific reactions. Thus, EIA was shown to be a very suitable test for routine detection of rotaviral antibodies in serum. Results of neutralization tests suggested that the monkeys (mostly rhesus macaques) in the present study were infected with viruses varying in their antigenic relatedness to SA 11 virus and to a British isolate of calf rotavirus.", "contents": "Rotavirus antibody assays on monkey sera: a comparison of enzyme immunoassay with neutralization and complement-fixation tests. An enzyme immunoassay (EIA) for the detection of rotaviral antibodies was developed, using a purified, cell culture-grown SA 11 viral antigen and alkaline phosphatase as an enzyme label. This technique was evaluated by comparative testing with tube neutralization and complement-fixation assays on a collection of simian sera. There was close correlation between positive and negative results obtained by EIA and by neutralization. The EIA was as easy to perform as complement fixation testing, but showed greater sensitivity and fewer nonspecific reactions. Thus, EIA was shown to be a very suitable test for routine detection of rotaviral antibodies in serum. Results of neutralization tests suggested that the monkeys (mostly rhesus macaques) in the present study were infected with viruses varying in their antigenic relatedness to SA 11 virus and to a British isolate of calf rotavirus."}
{"id": "PMID:230761", "title": "Egg transmission of avian adenovirus-associated virus and CELO virus during a naturally occurring infection.", "content": "Both avian adenovirus-associated virus (A-AV) and CELO virus were isolated from the embryonating eggs of 25-week-old black sex-linked hens during a naturally occurring infection. In the first 7 days of egg collection, A-AV was isolated from 10 of 43 (23.2%) embryonating eggs, and CELO virus was isolated from 8 of 43 (18.6%) embryonating eggs. Both viruses were isolated from six eggs. In the next 16 days of egg collection, A-AV and CELO virus were coisolated from 1 of 127 (0.8%) eggs; all other samples were negative for both viruses. All six hens transmitting A-AV to eggs and 5 of 6 hens transmitting CELO virus showed seroconversions (fourfold increase in antibody concentrations). Viruses were not isolated from eggs after the hens showed a fourfold increase in antibody concentrations.", "contents": "Egg transmission of avian adenovirus-associated virus and CELO virus during a naturally occurring infection. Both avian adenovirus-associated virus (A-AV) and CELO virus were isolated from the embryonating eggs of 25-week-old black sex-linked hens during a naturally occurring infection. In the first 7 days of egg collection, A-AV was isolated from 10 of 43 (23.2%) embryonating eggs, and CELO virus was isolated from 8 of 43 (18.6%) embryonating eggs. Both viruses were isolated from six eggs. In the next 16 days of egg collection, A-AV and CELO virus were coisolated from 1 of 127 (0.8%) eggs; all other samples were negative for both viruses. All six hens transmitting A-AV to eggs and 5 of 6 hens transmitting CELO virus showed seroconversions (fourfold increase in antibody concentrations). Viruses were not isolated from eggs after the hens showed a fourfold increase in antibody concentrations."}
{"id": "PMID:230762", "title": "A seroepizootiologic study of five viruses in a swine-evaluation station.", "content": "This serologic study was done to gain information on the spread, maintenance, and effect upon performance of five porcine viruses. Blood samples were taken from two groups of 8- to 11-week-old pigs from a large number of Indiana swine herds in a performance-testing station 1 week after entry, 7 weeks after entry (one group only), and at slaughter. The sera were tested by indirect fluorescent antibody tests for antibodies to transmissible gastroenteritis virus (TGEV), swine influenza virus (SIV), hemagglutinating encephalomyelitis virus (HEV), porcine adenovirus (PAV), and pseudorabies virus (PRV). Seroconversions to TGEV, HEV, and PAV occurred in a group of pigs entered in May and slaughtered in August (group 1). In the group that was entered in October and slaughtered in January (group 2), pigs developed antibodies to SIV, HEV, and PAV, but not to TGEV. Only 1 of the 434 pigs tested had antibodies to PRV, and there were no seroconversions to this virus. The only statistically valid effect of infection on performance was found in group 1 pigs, which had seroconverted to TGEV during the first 7 weeks of their stay. These pigs gained 0.077 kg less per day than pigs that did not develop antibodies to TGEV during that period. The pattern of serologic reactions was indicative of a relatively slow spread of these viruses in the groups. We interpret this as supporting the concept that a relatively slow spread of these viruses through large groups of pigs kept under conditions that are less than optimum for virus spread may be an important means of their interepizootic survival.", "contents": "A seroepizootiologic study of five viruses in a swine-evaluation station. This serologic study was done to gain information on the spread, maintenance, and effect upon performance of five porcine viruses. Blood samples were taken from two groups of 8- to 11-week-old pigs from a large number of Indiana swine herds in a performance-testing station 1 week after entry, 7 weeks after entry (one group only), and at slaughter. The sera were tested by indirect fluorescent antibody tests for antibodies to transmissible gastroenteritis virus (TGEV), swine influenza virus (SIV), hemagglutinating encephalomyelitis virus (HEV), porcine adenovirus (PAV), and pseudorabies virus (PRV). Seroconversions to TGEV, HEV, and PAV occurred in a group of pigs entered in May and slaughtered in August (group 1). In the group that was entered in October and slaughtered in January (group 2), pigs developed antibodies to SIV, HEV, and PAV, but not to TGEV. Only 1 of the 434 pigs tested had antibodies to PRV, and there were no seroconversions to this virus. The only statistically valid effect of infection on performance was found in group 1 pigs, which had seroconverted to TGEV during the first 7 weeks of their stay. These pigs gained 0.077 kg less per day than pigs that did not develop antibodies to TGEV during that period. The pattern of serologic reactions was indicative of a relatively slow spread of these viruses in the groups. We interpret this as supporting the concept that a relatively slow spread of these viruses through large groups of pigs kept under conditions that are less than optimum for virus spread may be an important means of their interepizootic survival."}
{"id": "PMID:230763", "title": "Temporal appearance, geographic distribution, and species of origin of bluetongue virus serotypes in the United States.", "content": "Beginning in 1973, all available laboratory and field strains of bluetongue virus (BTV) from the United States were serotyped. Of the viral strains serotyped, 27 were collected from 1953 through 1972; 173 were collected from 1973 through 1977. Although 20 BTV serotypes have been found worldwide, only BTV serotypes 10, 11, 13, and 17 have been found in the United States. Since 1973, serotypes 11 and 17 have been the prevalent serotypes. Samples were collected over a 24-year period in the United States and represent a wide geographic area and diverse host sources (sheep, cattle, wild ruminants, and insect vectors). The collection was not a statistical sampling.", "contents": "Temporal appearance, geographic distribution, and species of origin of bluetongue virus serotypes in the United States. Beginning in 1973, all available laboratory and field strains of bluetongue virus (BTV) from the United States were serotyped. Of the viral strains serotyped, 27 were collected from 1953 through 1972; 173 were collected from 1973 through 1977. Although 20 BTV serotypes have been found worldwide, only BTV serotypes 10, 11, 13, and 17 have been found in the United States. Since 1973, serotypes 11 and 17 have been the prevalent serotypes. Samples were collected over a 24-year period in the United States and represent a wide geographic area and diverse host sources (sheep, cattle, wild ruminants, and insect vectors). The collection was not a statistical sampling."}
{"id": "PMID:230766", "title": "In vitro cultivation of Anaplasma marginale: growth pattern and morphologic appearance.", "content": "Anaplasma marginale propagated in vitro showed an increasing rate of replication in a sequence of three experiments. The changes in the percentage of parasitized erythrocytes and identification of the organism in culture were monitored by the Giemsa-staining and the direct fluorescent antibody techniques. The ultrastructure of the organism in culture also was determined. The percentage of parasitized erythrocytes increased more than three times in the first experiment during a period of 8 days, and about ten times in the second experiment during a period of 14 days. After 8 days of observation of the primary culture in the third experiment, the trend of growth was more rapid than in the first and second experiment. The viability of the organism was verified by inoculation of susceptible calves, using 13- and 33-day cultures of the first and the second experiments, respectively. The primary cultures were subcultured twice by dilution with normal bovine erythrocytes.", "contents": "In vitro cultivation of Anaplasma marginale: growth pattern and morphologic appearance. Anaplasma marginale propagated in vitro showed an increasing rate of replication in a sequence of three experiments. The changes in the percentage of parasitized erythrocytes and identification of the organism in culture were monitored by the Giemsa-staining and the direct fluorescent antibody techniques. The ultrastructure of the organism in culture also was determined. The percentage of parasitized erythrocytes increased more than three times in the first experiment during a period of 8 days, and about ten times in the second experiment during a period of 14 days. After 8 days of observation of the primary culture in the third experiment, the trend of growth was more rapid than in the first and second experiment. The viability of the organism was verified by inoculation of susceptible calves, using 13- and 33-day cultures of the first and the second experiments, respectively. The primary cultures were subcultured twice by dilution with normal bovine erythrocytes."}
{"id": "PMID:230767", "title": "Safety and efficacy studies of live- and killed-feline leukemia virus vaccines.", "content": "The safety and the efficacy of several feline leukemia virus (FeLV) vaccines for 16-week-old kittens were determined. Vaccines were derived from an FL74 lymphoblastoid cell line that has been in continuous tissue culture passage for about 4 years. The vaccines were made from living virus, formaldehyde-inactivated whole FL74 cells, and formaldehyde-inactivated whole virus. The efficacy of each produced vaccine was determined by challenge exposure of vaccinated cats with virulent FeLV. The two formaldehyde-inactivated vaccines were found to be safe for use in kittens. Neither vaccine produce a significant feline oncornavirus-associated cell membrane antigen or virus-neutralizing antibody response, nor did they prevent infection with virulent FeLV. The inactivated whole-virus vaccine, however, did substantially decrease the proportion of kittens infected with virulent FeLV that became persistently viremic. In contrast, the whole FL74 cell vaccine did not reduce the number of infected kittens that became persistently viremic. The live-virus vaccine was found to be both safe and efficacious. About a half of the kittens vaccinated with live virus had transient bone marrow infection that lasted from 2 to 4 weeks. Viral antigen was not detected in peripheral blood, and infective virus was not shed in saliva, urine, or feces during the period that the vaccinal virus could be recovered from the bone marrow. In addition, there was no horizontal spread of vaccinal virus from vaccinated to non-vaccinated cagemates. Within several weeks, vaccinated kittens demonstrated no clinical or hematologic abnormalities and had high serum levels of feline oncornavirus-associated cell membrane antigen and virus-neutralizing antibody. Kittens vaccinated with living FeLV were resistant to infection with virulent virus.", "contents": "Safety and efficacy studies of live- and killed-feline leukemia virus vaccines. The safety and the efficacy of several feline leukemia virus (FeLV) vaccines for 16-week-old kittens were determined. Vaccines were derived from an FL74 lymphoblastoid cell line that has been in continuous tissue culture passage for about 4 years. The vaccines were made from living virus, formaldehyde-inactivated whole FL74 cells, and formaldehyde-inactivated whole virus. The efficacy of each produced vaccine was determined by challenge exposure of vaccinated cats with virulent FeLV. The two formaldehyde-inactivated vaccines were found to be safe for use in kittens. Neither vaccine produce a significant feline oncornavirus-associated cell membrane antigen or virus-neutralizing antibody response, nor did they prevent infection with virulent FeLV. The inactivated whole-virus vaccine, however, did substantially decrease the proportion of kittens infected with virulent FeLV that became persistently viremic. In contrast, the whole FL74 cell vaccine did not reduce the number of infected kittens that became persistently viremic. The live-virus vaccine was found to be both safe and efficacious. About a half of the kittens vaccinated with live virus had transient bone marrow infection that lasted from 2 to 4 weeks. Viral antigen was not detected in peripheral blood, and infective virus was not shed in saliva, urine, or feces during the period that the vaccinal virus could be recovered from the bone marrow. In addition, there was no horizontal spread of vaccinal virus from vaccinated to non-vaccinated cagemates. Within several weeks, vaccinated kittens demonstrated no clinical or hematologic abnormalities and had high serum levels of feline oncornavirus-associated cell membrane antigen and virus-neutralizing antibody. Kittens vaccinated with living FeLV were resistant to infection with virulent virus."}
{"id": "PMID:230768", "title": "Morphologic changes in the bursa of fabricius of chickens after inoculation with infectious bursal disease virus.", "content": "Sequential morphologic changes in the bursa of Fabricius were studied after oral inoculation of 1-day-old chicks with infectious bursal disease virus (IBDV). The epithelial surface morphology was studied by scanning electron microscopy, whereas the IBDV replication was sequentially followed by immunofluorescence and transmission electron microscopy. The earliest detectable changes in the bursal epithelium were evident at postinoculation hour (PIH) 48. They were characterized by reduction in numbers and size of microvilli on the epithelial cells accompanied by gradual involution of the button-like bursal follicles. At PIH 96 some specimens showed localized surface erosions due to loss of epithelial cells. As the damage progressed, the infolding of the buttomlike follicles became more pronounced and the surface erosions became more extensive. Loss of surface epithelium exposed the underlying damaged bursal follicles which appeared to be bounded by columnar epithelium. Some follicles had lost almost all the lymphocytes and macrophages and appeared as empty craters. Intrafollicular replication of IBDV was detectable as early as PIH 24 by immunofluorescence technique. Viral replication primarily took place in the lymphoid follicles. Regeneration of the follicles was not seen up to postinoculation day 12, suggesting that the IBDV-induced bursal damage could be permanent.", "contents": "Morphologic changes in the bursa of fabricius of chickens after inoculation with infectious bursal disease virus. Sequential morphologic changes in the bursa of Fabricius were studied after oral inoculation of 1-day-old chicks with infectious bursal disease virus (IBDV). The epithelial surface morphology was studied by scanning electron microscopy, whereas the IBDV replication was sequentially followed by immunofluorescence and transmission electron microscopy. The earliest detectable changes in the bursal epithelium were evident at postinoculation hour (PIH) 48. They were characterized by reduction in numbers and size of microvilli on the epithelial cells accompanied by gradual involution of the button-like bursal follicles. At PIH 96 some specimens showed localized surface erosions due to loss of epithelial cells. As the damage progressed, the infolding of the buttomlike follicles became more pronounced and the surface erosions became more extensive. Loss of surface epithelium exposed the underlying damaged bursal follicles which appeared to be bounded by columnar epithelium. Some follicles had lost almost all the lymphocytes and macrophages and appeared as empty craters. Intrafollicular replication of IBDV was detectable as early as PIH 24 by immunofluorescence technique. Viral replication primarily took place in the lymphoid follicles. Regeneration of the follicles was not seen up to postinoculation day 12, suggesting that the IBDV-induced bursal damage could be permanent."}
{"id": "PMID:230769", "title": "Antigenic variation among strains of the New Jersey serotype of vesicular stomatitis virus.", "content": "Four strains of vesicular stomatitis virus--New Jersey (Hazelhurst, Guatemala, Panama, and Concan) were compared by cross-neutralization and complement-fixation tests. They were indistinguishable by complement-fixation test; however, by plaque-reduction neutralization method, slight antigenic differences were observed between the Hazelhurst and the three other strains. It is concluded that these antigenic differences are insufficient to warrant reclassification of vesicular stomatitis virus--New Jersey into two distinct subtypes, as has been recently proposed.", "contents": "Antigenic variation among strains of the New Jersey serotype of vesicular stomatitis virus. Four strains of vesicular stomatitis virus--New Jersey (Hazelhurst, Guatemala, Panama, and Concan) were compared by cross-neutralization and complement-fixation tests. They were indistinguishable by complement-fixation test; however, by plaque-reduction neutralization method, slight antigenic differences were observed between the Hazelhurst and the three other strains. It is concluded that these antigenic differences are insufficient to warrant reclassification of vesicular stomatitis virus--New Jersey into two distinct subtypes, as has been recently proposed."}
{"id": "PMID:230770", "title": "An immunodiffusion test for detection of bovine viral diarrhea virus antibodies in bovine serum.", "content": "An immunodiffusion test (IDT) was developed for detecting bovine viral diarrhea virus antibodies in bovine serum. The antigen utilized in the IDT was prepared from bovine viral diarrhea virus-infected monolayer cultures. Results of the IDT were obtained within 48 hours and correlated with the virus-neutralization test.", "contents": "An immunodiffusion test for detection of bovine viral diarrhea virus antibodies in bovine serum. An immunodiffusion test (IDT) was developed for detecting bovine viral diarrhea virus antibodies in bovine serum. The antigen utilized in the IDT was prepared from bovine viral diarrhea virus-infected monolayer cultures. Results of the IDT were obtained within 48 hours and correlated with the virus-neutralization test."}
{"id": "PMID:230772", "title": "Pathology of the placenta and newborn pups with suspected intrauterine infection of canine herpesvirus.", "content": "Pathologic and virologic investigations were done on the fetal placenta and on pup runts which were obtained from a bitch with a medical history of canine herpesvirus (CHV) infection. Macroscopically, the placenta was poorly developed. Small grayish white foci were observed in the placental labyrinth. Characteristic lesions of CHV infection were not prominent in the pups examined. Microscopically, however, focal degenerative and necrotizing lesions were observed in the placental labyrinth. Rarely, eosinophilic or basophilic intranuclear inclusion bodies were in the trophoblastic cells in the necrotizing lesions. In the adrenal gland of one stillborn pup, focal necrosis and hemorrhages could be seen; these irregularities were essentially the same as those seen in the newborn pups with CHV infection. Focal interstitial pneumonia was also observed in some of the pups. The CHV organism was isolated from the kidney of one pup that survived for 22 days.", "contents": "Pathology of the placenta and newborn pups with suspected intrauterine infection of canine herpesvirus. Pathologic and virologic investigations were done on the fetal placenta and on pup runts which were obtained from a bitch with a medical history of canine herpesvirus (CHV) infection. Macroscopically, the placenta was poorly developed. Small grayish white foci were observed in the placental labyrinth. Characteristic lesions of CHV infection were not prominent in the pups examined. Microscopically, however, focal degenerative and necrotizing lesions were observed in the placental labyrinth. Rarely, eosinophilic or basophilic intranuclear inclusion bodies were in the trophoblastic cells in the necrotizing lesions. In the adrenal gland of one stillborn pup, focal necrosis and hemorrhages could be seen; these irregularities were essentially the same as those seen in the newborn pups with CHV infection. Focal interstitial pneumonia was also observed in some of the pups. The CHV organism was isolated from the kidney of one pup that survived for 22 days."}
{"id": "PMID:230773", "title": "Experimental infection of eastern cottontail rabbits Sylvilagus floridanus) with infectious bovine rhinotracheitis virus.", "content": "Experimental infection of eastern cottontail rabbits (Sylvilagus floridanus) with infectious bovine rhinotracheitis virus caused acute keratoconjunctivitis and a fatal systemic infection. The clinical syndrome was characterized initially by blepharospasm and ocular discharge. The rabbits were markedly depressed on post-exposure day (PED) 5 and were dead or moribund on PED 6. The virus was readily recovered from liver and adrenal gland tissue on PED 6 and from conjunctival swabs on PED 1 to 6. Histopathologic studies revealed a few necrotic foci in the liver and multiple focal to diffuse necrosis of the adrenal glands. Viral isolation and immunofluorescence tests were used to demonstrate a direct association between infectious bovine rhinotracheitis viral antigens and the lesions.", "contents": "Experimental infection of eastern cottontail rabbits Sylvilagus floridanus) with infectious bovine rhinotracheitis virus. Experimental infection of eastern cottontail rabbits (Sylvilagus floridanus) with infectious bovine rhinotracheitis virus caused acute keratoconjunctivitis and a fatal systemic infection. The clinical syndrome was characterized initially by blepharospasm and ocular discharge. The rabbits were markedly depressed on post-exposure day (PED) 5 and were dead or moribund on PED 6. The virus was readily recovered from liver and adrenal gland tissue on PED 6 and from conjunctival swabs on PED 1 to 6. Histopathologic studies revealed a few necrotic foci in the liver and multiple focal to diffuse necrosis of the adrenal glands. Viral isolation and immunofluorescence tests were used to demonstrate a direct association between infectious bovine rhinotracheitis viral antigens and the lesions."}
{"id": "PMID:230774", "title": "Mortality among shipyard workers in Genoa, Italy.", "content": "The dockyards of Genoa are exposed to many known or suspect carcinogenic agents, namely, asbestos, silica, polycyclic aromatic hydrocarbons, and halogenated hydrocarbons; other possibly harmful substances are trace amounts of aromatic amines, welding smokes, paints, and lipid-removing solvents. A cohort study of causes of death of 2190 dockyard workers in Genoa was conducted between January 1, 1960 and December 31, 1975. Mortality rates were calculated for 20 different occupational categories, for which there exist different levels of exposure to noxious substances. Two control groups were selected: the general male population of Genoa and all male employees (462) of San Martino Hospital, Genoa for the same period of time. Causes of death that demonstrated significant excesses for both control groups were: cancer of the colon, excluding the rectum; cancer of the larynx; cancer of the lung, bronchus, and trachea; cancer of the kidney, urinary bladder, and other urinary organs; respiratory diseases; and cirrhosis of the liver. The data obtained from these 20 job categories revealed different types and levels of risk for various carcinogenic agents.", "contents": "Mortality among shipyard workers in Genoa, Italy. The dockyards of Genoa are exposed to many known or suspect carcinogenic agents, namely, asbestos, silica, polycyclic aromatic hydrocarbons, and halogenated hydrocarbons; other possibly harmful substances are trace amounts of aromatic amines, welding smokes, paints, and lipid-removing solvents. A cohort study of causes of death of 2190 dockyard workers in Genoa was conducted between January 1, 1960 and December 31, 1975. Mortality rates were calculated for 20 different occupational categories, for which there exist different levels of exposure to noxious substances. Two control groups were selected: the general male population of Genoa and all male employees (462) of San Martino Hospital, Genoa for the same period of time. Causes of death that demonstrated significant excesses for both control groups were: cancer of the colon, excluding the rectum; cancer of the larynx; cancer of the lung, bronchus, and trachea; cancer of the kidney, urinary bladder, and other urinary organs; respiratory diseases; and cirrhosis of the liver. The data obtained from these 20 job categories revealed different types and levels of risk for various carcinogenic agents."}
{"id": "PMID:230778", "title": "[Surgical treatment of chemodectomas of the neck (author's transl)].", "content": "About 16 cases of chemodectomas of the neck, with surgical management during the five past years, the authors present an actualisation about surgery of these tumors of the paraganglionnary system at the level of the neck. After recording the different means of the diagnosis, particulary carotid arteriography, they insist about the necessity of a complete excision of these tumors because of local risks due to the neurovascular compression and infiltration, and because of general risks due to malignant metastasis. Three major risks run with surgery in these cases: hemorrhagic, neurologic, and vascular risks (because of the possible extension to the carotidian axis). 14 total excisions and 1 incomplete excision were performed; 1 no-operated tumor was noted because of the death of the patient before surgery due to a metastatis paraplegia. 4 resections of the carotidian axis with 1 repair by end to end anastomosis and 3 by a vein graft were necessary. No mortality after surgery in these patients was encountered. No recurence, no metastatic phenomen in our patients after the total excision of the primary chemodectoma of the neck even for one histologically maligant tumor, three years ago.", "contents": "[Surgical treatment of chemodectomas of the neck (author's transl)]. About 16 cases of chemodectomas of the neck, with surgical management during the five past years, the authors present an actualisation about surgery of these tumors of the paraganglionnary system at the level of the neck. After recording the different means of the diagnosis, particulary carotid arteriography, they insist about the necessity of a complete excision of these tumors because of local risks due to the neurovascular compression and infiltration, and because of general risks due to malignant metastasis. Three major risks run with surgery in these cases: hemorrhagic, neurologic, and vascular risks (because of the possible extension to the carotidian axis). 14 total excisions and 1 incomplete excision were performed; 1 no-operated tumor was noted because of the death of the patient before surgery due to a metastatis paraplegia. 4 resections of the carotidian axis with 1 repair by end to end anastomosis and 3 by a vein graft were necessary. No mortality after surgery in these patients was encountered. No recurence, no metastatic phenomen in our patients after the total excision of the primary chemodectoma of the neck even for one histologically maligant tumor, three years ago."}
{"id": "PMID:230779", "title": "Affinity electrophoresis of human alcohol dehydrogenase (ADH) isozymes.", "content": "1. The effects of coenzyme NAD and related compounds on the electrophoretic properties of the human ADH isozymes have been examined by the technique of affinity electrophoresis. 2. Incorporation of NAD, NADH or AMP into a starch-gel matrix leads to retardation in the cathodal mobilities of the gamma 2 gamma 2 and alpha alpha isozymes, but not the beta 1 beta 1 and gamma 1 gamma 1 isozymes. The heterodimeric isozymes show intermediate effects, and the genetic polymorphism at the ADH3 locus is only discernible if electrophoresis is carried out in the presence of coenzyme. 3. The behaviour of the ioszymes can be attributed to slight differences between the products (alpha, beta 1 and gamma 1) of the common alleles at the three ADH loci and a pronounced difference between the products (gamma 1 and gamma 2) of the alternative alleles at the ADH3 locus in their affinities for the cofactor NAD.", "contents": "Affinity electrophoresis of human alcohol dehydrogenase (ADH) isozymes. 1. The effects of coenzyme NAD and related compounds on the electrophoretic properties of the human ADH isozymes have been examined by the technique of affinity electrophoresis. 2. Incorporation of NAD, NADH or AMP into a starch-gel matrix leads to retardation in the cathodal mobilities of the gamma 2 gamma 2 and alpha alpha isozymes, but not the beta 1 beta 1 and gamma 1 gamma 1 isozymes. The heterodimeric isozymes show intermediate effects, and the genetic polymorphism at the ADH3 locus is only discernible if electrophoresis is carried out in the presence of coenzyme. 3. The behaviour of the ioszymes can be attributed to slight differences between the products (alpha, beta 1 and gamma 1) of the common alleles at the three ADH loci and a pronounced difference between the products (gamma 1 and gamma 2) of the alternative alleles at the ADH3 locus in their affinities for the cofactor NAD."}
{"id": "PMID:230780", "title": "The Scianna blood group lies distal to uridine monophosphate kinase on chromosome 1p.", "content": "Linkage between the Scianna blood group and the Rhesus blood group has been confirmed. Families demonstrating recombinants between U M P K and Sc suggest that U M P K lies between Sc and PGM1.", "contents": "The Scianna blood group lies distal to uridine monophosphate kinase on chromosome 1p. Linkage between the Scianna blood group and the Rhesus blood group has been confirmed. Families demonstrating recombinants between U M P K and Sc suggest that U M P K lies between Sc and PGM1."}
{"id": "PMID:230776", "title": "[The endaural approach and surgery of glomus jugulare tumors (5 cases)].", "content": "The endaural approach has its in excision surgery of certain forms of jugular glomus tumor. --In the pure, tympanic form, a minimal or extended endaural approach is perfectly suitable. -- In tympano-mastoid forms, without involvement or with minimal involvement of the jugular foramen, a prolonged endaural approach may be used for wider operations involving the whole middle ear and mastoid around a bony aqueduct or an exposed VII. --Nevertheless, in the presence of tympano-jugular or tympano-masto-jugular forms, with marked involvement of jugular foramen, the greatest caution is necessary. It would appear that the endaural route may still be suggested but only for certain tumors, with the express reserve that angiographic studies defining its site and extent are favourable. By virtue of more and more highly developed techniques of exploration (scanner with contrast, films in subtraction) which may be used for measurement and precise localization of the tumor, indications for the type of approach may now be defined with even more precision. --It should be noted that if there is the slightest doubt, the slightest reserve, or the slightest fear that an endaural approach might be inadequate to deal with the situation, it should be definitely avoided with preference for a cervico-retro-auricular or cervicopre and retro-auricular approach, or radiotherapy only, or even abstenstion from operation, with observation. It is only if such rules of good sense and caution are respected that minimal, extended, prolonged endaural approaches will retain a worthy place in the surgical treatment of jugular glomus tumors.", "contents": "[The endaural approach and surgery of glomus jugulare tumors (5 cases)]. The endaural approach has its in excision surgery of certain forms of jugular glomus tumor. --In the pure, tympanic form, a minimal or extended endaural approach is perfectly suitable. -- In tympano-mastoid forms, without involvement or with minimal involvement of the jugular foramen, a prolonged endaural approach may be used for wider operations involving the whole middle ear and mastoid around a bony aqueduct or an exposed VII. --Nevertheless, in the presence of tympano-jugular or tympano-masto-jugular forms, with marked involvement of jugular foramen, the greatest caution is necessary. It would appear that the endaural route may still be suggested but only for certain tumors, with the express reserve that angiographic studies defining its site and extent are favourable. By virtue of more and more highly developed techniques of exploration (scanner with contrast, films in subtraction) which may be used for measurement and precise localization of the tumor, indications for the type of approach may now be defined with even more precision. --It should be noted that if there is the slightest doubt, the slightest reserve, or the slightest fear that an endaural approach might be inadequate to deal with the situation, it should be definitely avoided with preference for a cervico-retro-auricular or cervicopre and retro-auricular approach, or radiotherapy only, or even abstenstion from operation, with observation. It is only if such rules of good sense and caution are respected that minimal, extended, prolonged endaural approaches will retain a worthy place in the surgical treatment of jugular glomus tumors."}
{"id": "PMID:230781", "title": "Familial subacute necrotizing encephalomyelopathy of the adult form (adult Leigh syndrome).", "content": "A family--mother and 2 sons--with a heredodegenerative neurological disease is described. The disease started with bilateral optic atrophy, central scotoma, and color blindness during the second decade. This was followed by a quiescent period until additional neurological symptoms appeared, around the age of 50 years in the case of the mother and 40 and 30 years, respectively, in the sons. The additional symptoms were ataxia, spastic paresis, clonic jerks, grand mal seizures, psychia lability, and slight dementia. The disease was progressive, resulting in permanent hospitalization within a few years. The mother died at the age of 63 years and the sons at 46 and 43 years of age. Neuropathological examination revealed lesions histopathologically characteristic of subacute necrotizing encephalomyelopathy (SNE, Leigh disease), and their distribution in the brain and brainstem also conformed to this disease. On the basis of the clinical course and neuropathological findings, we consider that these 3 patients represent the first reported familial cases of the adult form of SNE.", "contents": "Familial subacute necrotizing encephalomyelopathy of the adult form (adult Leigh syndrome). A family--mother and 2 sons--with a heredodegenerative neurological disease is described. The disease started with bilateral optic atrophy, central scotoma, and color blindness during the second decade. This was followed by a quiescent period until additional neurological symptoms appeared, around the age of 50 years in the case of the mother and 40 and 30 years, respectively, in the sons. The additional symptoms were ataxia, spastic paresis, clonic jerks, grand mal seizures, psychia lability, and slight dementia. The disease was progressive, resulting in permanent hospitalization within a few years. The mother died at the age of 63 years and the sons at 46 and 43 years of age. Neuropathological examination revealed lesions histopathologically characteristic of subacute necrotizing encephalomyelopathy (SNE, Leigh disease), and their distribution in the brain and brainstem also conformed to this disease. On the basis of the clinical course and neuropathological findings, we consider that these 3 patients represent the first reported familial cases of the adult form of SNE."}
{"id": "PMID:230777", "title": "[Rare tumors of the septum. 8 reported cases (author's transl)].", "content": "The authors present 8 cases of rare tumors of the nasal septum and define a number of characteristic points on the basis of each of them. The following are presented: --a malignant nevus, the rarety of E.N.T. sites of such tumors is emphasized, as well as important role of immunotherapy in their treatment, alongside surgery and radio-therapy. --a keratoacanthoma, difficult in terms of differential diagnosis from a basal cell carcinoma. -- a cavernous hemangioma, excision of which must be wide if recurrence is to be avoided. --one very hemorrhagic mixed tumor. --one case of pseudo tumoral tuberculosis in a woman with no known past history of tuberculous disease. --one very painful glomus tumor, radical treatment of which is surgical, in preference to radiotherapy. --two cylindromas of the septum, one taking the form of a large, angiomatous polyp, which puts in question the name of cystic adenoid carcinoma, suggested for these non-cutaneous tumors.", "contents": "[Rare tumors of the septum. 8 reported cases (author's transl)]. The authors present 8 cases of rare tumors of the nasal septum and define a number of characteristic points on the basis of each of them. The following are presented: --a malignant nevus, the rarety of E.N.T. sites of such tumors is emphasized, as well as important role of immunotherapy in their treatment, alongside surgery and radio-therapy. --a keratoacanthoma, difficult in terms of differential diagnosis from a basal cell carcinoma. -- a cavernous hemangioma, excision of which must be wide if recurrence is to be avoided. --one very hemorrhagic mixed tumor. --one case of pseudo tumoral tuberculosis in a woman with no known past history of tuberculous disease. --one very painful glomus tumor, radical treatment of which is surgical, in preference to radiotherapy. --two cylindromas of the septum, one taking the form of a large, angiomatous polyp, which puts in question the name of cystic adenoid carcinoma, suggested for these non-cutaneous tumors."}
{"id": "PMID:230782", "title": "Disturbances of rapid-eye-movement sleep in 3 brothers with Pelizaeus-Merzbacher disease.", "content": "The electrophysiological features of 3 brothers with the classic form of Pelizaeus-Merzbacher disease (PMD) were studied. Two consecutive overnight polygraphic sleep recordings indicated a gross distortion of rapid-eye-movement (REM) sleep for all patients. A lower than normal percentage of REM sleep in these patients was consistent with their retarded intellectual development, which supports current thinking that REM sleep may be a sensitive index of brain function integrity. Non-rapid-eye-movement (NREM) sleep, in contrast to reported findings in 1 patient with PMD, was uniformly characterized by distinct stages in which the electroencephalograms contained frequent vertex waves and spindles. Tests of peripheral nerve conduction velocity, acoustic brainstem reflexes, and visual and auditory evoked potentials did not indicate any abnormalities, nor did electroencephalograms obtained during wakefulness. One patient did have epileptiform spikes and spike waves recorded during an all-night EEG, an unusual finding in a child with cerebral white matter disease.", "contents": "Disturbances of rapid-eye-movement sleep in 3 brothers with Pelizaeus-Merzbacher disease. The electrophysiological features of 3 brothers with the classic form of Pelizaeus-Merzbacher disease (PMD) were studied. Two consecutive overnight polygraphic sleep recordings indicated a gross distortion of rapid-eye-movement (REM) sleep for all patients. A lower than normal percentage of REM sleep in these patients was consistent with their retarded intellectual development, which supports current thinking that REM sleep may be a sensitive index of brain function integrity. Non-rapid-eye-movement (NREM) sleep, in contrast to reported findings in 1 patient with PMD, was uniformly characterized by distinct stages in which the electroencephalograms contained frequent vertex waves and spindles. Tests of peripheral nerve conduction velocity, acoustic brainstem reflexes, and visual and auditory evoked potentials did not indicate any abnormalities, nor did electroencephalograms obtained during wakefulness. One patient did have epileptiform spikes and spike waves recorded during an all-night EEG, an unusual finding in a child with cerebral white matter disease."}
{"id": "PMID:230783", "title": "Growth inhibition by acycloguanosine of herpesviruses isolated from human infections.", "content": "Inhibition by acycloguanosine (ACG) of plaque formation by harpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus, and cytomegalovirus was studied. Seventeen clinical isolates of HSV-1 were inhibited by ACG at a mean 50% inhibitory dose (ID(50)) of 0.15 +/- 0.09 muM. The mean ID(50) for 10 isolates of HSV-2 was 1.62 +/- 0.76 muM, and for four isolates of varicella-zoster virus it was 3.75 +/- 1.30 muM. The ID(50)'s for two cytomegalovirus isolates were 100 and 160 muM, and for four additional isolates of cytomegalovirus no end point (ID(50)) was reached at 200 muM. ACG at a concentration of 200 muM had no effect on deoxyribonucleic acid synthesis in human fibroblast cells and only inhibited thymidine incorporation by Vero cells by one-third. These studies demonstrated the antiviral activity of ACG against clinical isolates of HSV-1, HSV-2, and varicella-zoster virus and the lack of toxicity to monkey or human cells in culture at concentrations which markedly inhibited these viruses. ACG had little effect on cytomegalovirus at concentrations in excess of 100 muM.", "contents": "Growth inhibition by acycloguanosine of herpesviruses isolated from human infections. Inhibition by acycloguanosine (ACG) of plaque formation by harpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus, and cytomegalovirus was studied. Seventeen clinical isolates of HSV-1 were inhibited by ACG at a mean 50% inhibitory dose (ID(50)) of 0.15 +/- 0.09 muM. The mean ID(50) for 10 isolates of HSV-2 was 1.62 +/- 0.76 muM, and for four isolates of varicella-zoster virus it was 3.75 +/- 1.30 muM. The ID(50)'s for two cytomegalovirus isolates were 100 and 160 muM, and for four additional isolates of cytomegalovirus no end point (ID(50)) was reached at 200 muM. ACG at a concentration of 200 muM had no effect on deoxyribonucleic acid synthesis in human fibroblast cells and only inhibited thymidine incorporation by Vero cells by one-third. These studies demonstrated the antiviral activity of ACG against clinical isolates of HSV-1, HSV-2, and varicella-zoster virus and the lack of toxicity to monkey or human cells in culture at concentrations which markedly inhibited these viruses. ACG had little effect on cytomegalovirus at concentrations in excess of 100 muM."}
{"id": "PMID:230784", "title": "Latent herpes simplex virus infections in sensory ganglia of hairless mice prevented by acycloguanosine.", "content": "Acycloguanosine (ACG) was able to prevent the fatal outcome of herpes simplex virus-induced skin infections of the lumbosacral or orofacila area in hairless mice. Topical ACG treatment was more effective than systemic treatment in preventing the evolution of skin lesions. Acute ganglionic infections in the trigeminal ganglia were prevented by ACG, and latent ganglionic infections did not become established when the ACG treatment was initiated 3 h after infection. Serum antibody titers were, on the average, eight times higher in mice which developed latent ganglionic infections after ACG treatment than in mice without evidence of herpes simplex virus latency in ganglia. Reinoculation of ACG-treated mice at a site different from that of the primary inoculation did not lead to the establishment of a second latent infection with the homologous virus type when a latent infection was already present. In mice without evidence of latent infection after the primary inoculation, a latent infection at the site of reinoculation became established in 25% of the animals.", "contents": "Latent herpes simplex virus infections in sensory ganglia of hairless mice prevented by acycloguanosine. Acycloguanosine (ACG) was able to prevent the fatal outcome of herpes simplex virus-induced skin infections of the lumbosacral or orofacila area in hairless mice. Topical ACG treatment was more effective than systemic treatment in preventing the evolution of skin lesions. Acute ganglionic infections in the trigeminal ganglia were prevented by ACG, and latent ganglionic infections did not become established when the ACG treatment was initiated 3 h after infection. Serum antibody titers were, on the average, eight times higher in mice which developed latent ganglionic infections after ACG treatment than in mice without evidence of herpes simplex virus latency in ganglia. Reinoculation of ACG-treated mice at a site different from that of the primary inoculation did not lead to the establishment of a second latent infection with the homologous virus type when a latent infection was already present. In mice without evidence of latent infection after the primary inoculation, a latent infection at the site of reinoculation became established in 25% of the animals."}
{"id": "PMID:230785", "title": "Structural and compositional changes associated with chlorine inactivation of polioviruses.", "content": "Chlorine inactivation of polioviruses resulted in the loss of viral ribonucleic acid, converting the viruses from 156S particles to 80S particles. However, it was found that virus inactivation occurred before the ribonucleic acid was released from the virions. Extraction of ribonucleic acid from partially inactivated virus suspensions indicated that chlorine inactivation was due to degradation of the ribonucleic acid before release and that ribonucleic acid loss was a secondary event. The empty 80S capsids had the same isoelectric point and ability to attach to host cells as infective virions. Thus, no major capsid conformational changes occurred during chlorine inactivation.", "contents": "Structural and compositional changes associated with chlorine inactivation of polioviruses. Chlorine inactivation of polioviruses resulted in the loss of viral ribonucleic acid, converting the viruses from 156S particles to 80S particles. However, it was found that virus inactivation occurred before the ribonucleic acid was released from the virions. Extraction of ribonucleic acid from partially inactivated virus suspensions indicated that chlorine inactivation was due to degradation of the ribonucleic acid before release and that ribonucleic acid loss was a secondary event. The empty 80S capsids had the same isoelectric point and ability to attach to host cells as infective virions. Thus, no major capsid conformational changes occurred during chlorine inactivation."}
{"id": "PMID:230786", "title": "Survival of enteric viruses under natural conditions in a subarctic river.", "content": "The survival of enteric viruses was studied in the vicinity of Fairbanks, Alaska at selected stations along a 317-km section of the Tanana River. This section was located downstream from all known domestic wastewater sources and was effectively sealed by a total ice cover. The mean flow time through the region was 7.1 days, during which initial viral population showed a relative survival rate of 34%. The tracing of native viruses at such great distances in the complete absence of other point and nonpoint viral sources has not been previously reported. Of the two methods of virus concentration used, viral recoveries from the disk adsorption virus elution procedure were far greater than those achieved with the Aquella system employed at that time. The fact the ratio of enteric viruses to fecal indicator bacteria was not constant clearly inferred that these bacteria were not an effectual measure of virus concentration. The persistence of fecal coliforms and fecal streptococci, however, attested to the microbiological health risk involved.", "contents": "Survival of enteric viruses under natural conditions in a subarctic river. The survival of enteric viruses was studied in the vicinity of Fairbanks, Alaska at selected stations along a 317-km section of the Tanana River. This section was located downstream from all known domestic wastewater sources and was effectively sealed by a total ice cover. The mean flow time through the region was 7.1 days, during which initial viral population showed a relative survival rate of 34%. The tracing of native viruses at such great distances in the complete absence of other point and nonpoint viral sources has not been previously reported. Of the two methods of virus concentration used, viral recoveries from the disk adsorption virus elution procedure were far greater than those achieved with the Aquella system employed at that time. The fact the ratio of enteric viruses to fecal indicator bacteria was not constant clearly inferred that these bacteria were not an effectual measure of virus concentration. The persistence of fecal coliforms and fecal streptococci, however, attested to the microbiological health risk involved."}
{"id": "PMID:230787", "title": "Microbiology of bruised tissue.", "content": "No significant differences could be found in the microbial quality of bruised and unbruised tissue provided that the two types of tissue were treated identically. This suggests that there is no good reason for the condemnation of bruised tissue, which could well be used in manufactured products.", "contents": "Microbiology of bruised tissue. No significant differences could be found in the microbial quality of bruised and unbruised tissue provided that the two types of tissue were treated identically. This suggests that there is no good reason for the condemnation of bruised tissue, which could well be used in manufactured products."}
{"id": "PMID:230788", "title": "[Influence of cyclic adenosine monophosphate on the migration of primordial germ cells of the anuran Amphibians (author's transl)].", "content": "After the treatment in toto of the embryos from various species of Anura by cAMP, the number of primordial germ cells (PGC) in genital ridges is strongly reduced; the most part of the PGC are found in the endoderm. A ventral implant of agar impregnated with a solution of cAMP attracts numerous PGC in the same way as grafted chordomesoderm. The chordomesoderm itself, incubated with 3'-5' cyclic nucleotide phosphodiesterase, then grafted on to the ventral area of normal embryos attracts very few PBC compared with the non-incubated chordomesoderm. The results are analyzed and discussed along the following hypothesis: the migration of the PGC of the Anura is guided by cAMP which, diffusing from the chordomesoderm, is distributed along a concentration gradient increasing in a ventrodorsal direction. The PGC go up the gradient by a chemiotactic mechanism and reach the dorsal parts of the embryo.", "contents": "[Influence of cyclic adenosine monophosphate on the migration of primordial germ cells of the anuran Amphibians (author's transl)]. After the treatment in toto of the embryos from various species of Anura by cAMP, the number of primordial germ cells (PGC) in genital ridges is strongly reduced; the most part of the PGC are found in the endoderm. A ventral implant of agar impregnated with a solution of cAMP attracts numerous PGC in the same way as grafted chordomesoderm. The chordomesoderm itself, incubated with 3'-5' cyclic nucleotide phosphodiesterase, then grafted on to the ventral area of normal embryos attracts very few PBC compared with the non-incubated chordomesoderm. The results are analyzed and discussed along the following hypothesis: the migration of the PGC of the Anura is guided by cAMP which, diffusing from the chordomesoderm, is distributed along a concentration gradient increasing in a ventrodorsal direction. The PGC go up the gradient by a chemiotactic mechanism and reach the dorsal parts of the embryo."}
{"id": "PMID:230789", "title": "Hepatitis A and Indian childhood cirrhosis.", "content": "Antibody to hepatitis A virus (anti-HAV) was found in 50% of patients with Indian childhood cirrhosis; this was not significantly different from the prevalence of anti-HAV in age- and sex-matched controls.", "contents": "Hepatitis A and Indian childhood cirrhosis. Antibody to hepatitis A virus (anti-HAV) was found in 50% of patients with Indian childhood cirrhosis; this was not significantly different from the prevalence of anti-HAV in age- and sex-matched controls."}
{"id": "PMID:230790", "title": "A specific ultrastructural marker for disseminated lipogranulomatosis (Faber).", "content": "An ultrastructural investigation of two cutaneous lesions in a two-year-old Turkish boy with disseminated lipogranulomatosis (Farber) revealed curvilinear bodies in fibroblasts, histiocytes, and endothelial cells; \"elongated membranes\" in fibroblasts and endothelial cells; \"zebra bodies\" in endothelial cells; and spindle-shaped bodies in Schwann cells. In peripheral lymphocytes only alterations of mitochondria (swelling and ruptured cristae) but no inclusion bodies were found. Curvilinear bodies were numerous and easily identifiable; they appear to be characteristic of Farber's disease, and naming them \"Farber bodies\" is proposed. The diagnosis of this ceramide storage disease, in which the histological examination is relatively unspecific, can therefore be confirmed ultrastructurally.", "contents": "A specific ultrastructural marker for disseminated lipogranulomatosis (Faber). An ultrastructural investigation of two cutaneous lesions in a two-year-old Turkish boy with disseminated lipogranulomatosis (Farber) revealed curvilinear bodies in fibroblasts, histiocytes, and endothelial cells; \"elongated membranes\" in fibroblasts and endothelial cells; \"zebra bodies\" in endothelial cells; and spindle-shaped bodies in Schwann cells. In peripheral lymphocytes only alterations of mitochondria (swelling and ruptured cristae) but no inclusion bodies were found. Curvilinear bodies were numerous and easily identifiable; they appear to be characteristic of Farber's disease, and naming them \"Farber bodies\" is proposed. The diagnosis of this ceramide storage disease, in which the histological examination is relatively unspecific, can therefore be confirmed ultrastructurally."}
{"id": "PMID:230791", "title": "In vitro and in vivo myocardial effects of a cyclic AMP phosphodiesterase inhibitor structurally related to natural cardenolides.", "content": "The myocardial effects of the lactonic deoxybenzoin glucoside, AP 10, an ATPases and cyclic AMP phosphodiesterases inhibitor, were investigated in vitro and in vivo. AP 10 showed marked positive inotropic effects on spontaneously beating frog and mammal isolated hearts. This drug induced a substantial increase in cyclic AMP atrial level comparable to that observed with papaverine in the rat. Its inotropic effects on stimulated rat left atria were moderate and suppressed by reserpine pretreatment, in contrast with papaverine inotropic effects which were not significantly modified. As papaverine (10(-5) M), AP 10 (10(-4) M) shifted to the left the atrial dose-response curve for isoproterenol. The positive inotropic effects of AP 10 were more pronounced at low calcium concentrations. Furthermore, AP 10 prolonged the time course of tension decline in stimulated rat left atria exposed to Ca++ free medium. AP 10 (1 mg/kg) did not induce any in vivo hemodynamic disturbance in both anaesthetized and conscious dogs and significantly improved ventricular automaticity in anaesthetized dogs (0.5 mg/kg). This drug was also compared to quinidine in two in vivo experimental arrhythmias. AP 10 was more effective than quinidine in preventing ouabain-induced arrhythmias in conscious rabbits and electrically-induced atrial fibrillation in conscious dogs. Despite its ATPases inhibiting properties and some structural similarities with cardiac glycosides, AP 10 did not show a typical \"digitalis-like\" pharmacological profile. It exhibited some of the myocardial features which characterize phosphodiesterase inhibitors as caffeine, papaverine or Ro 7-2956. An interesting particularity of AP 10 action was its capacity to prevent experimental arrhythmias.", "contents": "In vitro and in vivo myocardial effects of a cyclic AMP phosphodiesterase inhibitor structurally related to natural cardenolides. The myocardial effects of the lactonic deoxybenzoin glucoside, AP 10, an ATPases and cyclic AMP phosphodiesterases inhibitor, were investigated in vitro and in vivo. AP 10 showed marked positive inotropic effects on spontaneously beating frog and mammal isolated hearts. This drug induced a substantial increase in cyclic AMP atrial level comparable to that observed with papaverine in the rat. Its inotropic effects on stimulated rat left atria were moderate and suppressed by reserpine pretreatment, in contrast with papaverine inotropic effects which were not significantly modified. As papaverine (10(-5) M), AP 10 (10(-4) M) shifted to the left the atrial dose-response curve for isoproterenol. The positive inotropic effects of AP 10 were more pronounced at low calcium concentrations. Furthermore, AP 10 prolonged the time course of tension decline in stimulated rat left atria exposed to Ca++ free medium. AP 10 (1 mg/kg) did not induce any in vivo hemodynamic disturbance in both anaesthetized and conscious dogs and significantly improved ventricular automaticity in anaesthetized dogs (0.5 mg/kg). This drug was also compared to quinidine in two in vivo experimental arrhythmias. AP 10 was more effective than quinidine in preventing ouabain-induced arrhythmias in conscious rabbits and electrically-induced atrial fibrillation in conscious dogs. Despite its ATPases inhibiting properties and some structural similarities with cardiac glycosides, AP 10 did not show a typical \"digitalis-like\" pharmacological profile. It exhibited some of the myocardial features which characterize phosphodiesterase inhibitors as caffeine, papaverine or Ro 7-2956. An interesting particularity of AP 10 action was its capacity to prevent experimental arrhythmias."}
{"id": "PMID:230792", "title": "The effect of triamterene upon the rat kidney plasma membrane Na-K-ATP-ase activity.", "content": "Triamterene (2,4,7-triamino-6-phenylpteridine) is a potassium-sparing diuretic whose mechanism of action is not clear. Experiments were performed to study the effect of triamterene upon the activity of Na-K-ATP-ase in the kidney plasma membranes. This enzyme, dissolved within the membrane bilayer, has been considered to be a biochemical vehicle for the active transport of sodium across the cell membrane. Intact and adrenalectomized rats were subjected to a five-day treatment with triamterene in a daily dose of 1.5 mg/100 g body weight. Triamterene was also administered to a group of intact, salt-loaded, rats. The activity of Na-K-ATP-ase in the kidney plasma membranes of intact and adrenalectomized rats treated with triamterene was decreased by 22.4% (p less than 0.05) and 37.2% (p less than 0.05), respectively. The activity of Na-K-ATP-ase in the renal plasma membranes of intact, salt-loaded, rats underwent greater decrease--63% (p less than 0.05). If the decreased activity of Na-K-ATP-ase in the kidney plasma membranes of rats treated with triamterene manifested the diuretic action of triamterene, results obtained in adrenalectomized rats would suggest that triamterene acts directly on the kidney, not via the adrenal glands.", "contents": "The effect of triamterene upon the rat kidney plasma membrane Na-K-ATP-ase activity. Triamterene (2,4,7-triamino-6-phenylpteridine) is a potassium-sparing diuretic whose mechanism of action is not clear. Experiments were performed to study the effect of triamterene upon the activity of Na-K-ATP-ase in the kidney plasma membranes. This enzyme, dissolved within the membrane bilayer, has been considered to be a biochemical vehicle for the active transport of sodium across the cell membrane. Intact and adrenalectomized rats were subjected to a five-day treatment with triamterene in a daily dose of 1.5 mg/100 g body weight. Triamterene was also administered to a group of intact, salt-loaded, rats. The activity of Na-K-ATP-ase in the kidney plasma membranes of intact and adrenalectomized rats treated with triamterene was decreased by 22.4% (p less than 0.05) and 37.2% (p less than 0.05), respectively. The activity of Na-K-ATP-ase in the renal plasma membranes of intact, salt-loaded, rats underwent greater decrease--63% (p less than 0.05). If the decreased activity of Na-K-ATP-ase in the kidney plasma membranes of rats treated with triamterene manifested the diuretic action of triamterene, results obtained in adrenalectomized rats would suggest that triamterene acts directly on the kidney, not via the adrenal glands."}
{"id": "PMID:230793", "title": "Divergent effects of prostaglandin synthesis inhibitors on pulmonary cyclic 3', 5'-adenosine monophosphate and cyclic 3', 5'-guanosine monophosphate levels in untreated and histamine sensitized mice.", "content": "Prostaglandin synthesis inhibitors (indomethacin and acetylsalicylic acid) were studied in mice under control conditions and during a period of B. pertussis-induced increased sensitivity to histamine. These compounds were employed to inhibit the generation of prostaglandins and thus allow for analysis of prostaglandin participation in the heightened accumulation of pulmonary cyclic nucleotides in pertussis-sensitized mice. The results show that the two non-steroid antiinflammatory agents studied caused a reduction in basal cyclic GMP levels in pulmonary tissue of mice. Cyclic AMP levels were unaltered. Histamine raised cyclic  GMP levels in sensitized mice even in the presence of cyclo-oxygenase inhibition, but these rises never exceeded basal levels in mice that had not received cyclo-oxygenase inhibitors. It can be concluded that prostaglandin synthesis inhibitors suppress the cyclic GMP system.", "contents": "Divergent effects of prostaglandin synthesis inhibitors on pulmonary cyclic 3', 5'-adenosine monophosphate and cyclic 3', 5'-guanosine monophosphate levels in untreated and histamine sensitized mice. Prostaglandin synthesis inhibitors (indomethacin and acetylsalicylic acid) were studied in mice under control conditions and during a period of B. pertussis-induced increased sensitivity to histamine. These compounds were employed to inhibit the generation of prostaglandins and thus allow for analysis of prostaglandin participation in the heightened accumulation of pulmonary cyclic nucleotides in pertussis-sensitized mice. The results show that the two non-steroid antiinflammatory agents studied caused a reduction in basal cyclic GMP levels in pulmonary tissue of mice. Cyclic AMP levels were unaltered. Histamine raised cyclic  GMP levels in sensitized mice even in the presence of cyclo-oxygenase inhibition, but these rises never exceeded basal levels in mice that had not received cyclo-oxygenase inhibitors. It can be concluded that prostaglandin synthesis inhibitors suppress the cyclic GMP system."}
{"id": "PMID:230797", "title": "Adenylyl cyclase deficient cr-1 (Crisp) mutant of Neurospora crassa: cyclic AMP-dependent nutritional deficiencies.", "content": "The inability to synthesize cyclic AMP drastically affects the nutritional metabolism of Neurospora crassa. The adenylyl cyclase-less mutant cr-1 (crisp) did not utilize several carbon sources, including glycerol, mannitol, arabinose, and casaminoacids. However, in glucose or acetate it grew as well as the wild type. The following evidence suggested that these nutritional deficiencies were a direct result of the cr-1 mutation: (i), in crosses to wild type they segregated together with the crisp morphological marker; (ii), cyclic AMP added to the cr-1 mutant growth medium overcame the nutritional deficiencies; (iii), the cyclic AMP effect was specific for the crisp mutant, for it was not observed with the wild type, nor with a spontaneous glycerol-utilizing cr-1 strain.", "contents": "Adenylyl cyclase deficient cr-1 (Crisp) mutant of Neurospora crassa: cyclic AMP-dependent nutritional deficiencies. The inability to synthesize cyclic AMP drastically affects the nutritional metabolism of Neurospora crassa. The adenylyl cyclase-less mutant cr-1 (crisp) did not utilize several carbon sources, including glycerol, mannitol, arabinose, and casaminoacids. However, in glucose or acetate it grew as well as the wild type. The following evidence suggested that these nutritional deficiencies were a direct result of the cr-1 mutation: (i), in crosses to wild type they segregated together with the crisp morphological marker; (ii), cyclic AMP added to the cr-1 mutant growth medium overcame the nutritional deficiencies; (iii), the cyclic AMP effect was specific for the crisp mutant, for it was not observed with the wild type, nor with a spontaneous glycerol-utilizing cr-1 strain."}
{"id": "PMID:230798", "title": "Cellular proliferation, cellular death and atherosclerosis.", "content": "The multipotential smooth muscle cell (SMC) is the predominant cell in arterial media and intima, and the major cell type involved in proliferative lesions. Studies using a precursor of DNA, namely [3H] thymidine, and autoradiography have shown that proliferation of SMC is an important and early response to atherogenic stimuli, such as cholesterol feeding, surgically induced hypertension or endothelial injury. Cultures of aortic SMC offer excellent in vitro models to study the reactivity of these cells to recognized or suspected risk factors. Pure SMC cultures are obtained by placing small fragments of aortic media in a defined culture medium and their response evaluated by thymidine incorporation and/or increase in size of the outgrowing cell colony. Factors essential for adequate growth include normal serum constitutents, including the lipoproteins and a platelet derived factor. Replacing the normal serum with dietarily induced hyperlipemic serum results in greatly increased proliferation. The serum fraction largely responsible for this phenomenon is the low density lipoprotein. Simultaneous addition of high density lipoproteins partly suppress this reaction. Serum from diabetic or hypertensive--but normolipemic--animals similarly stimulates these cells to increased proliferation.", "contents": "Cellular proliferation, cellular death and atherosclerosis. The multipotential smooth muscle cell (SMC) is the predominant cell in arterial media and intima, and the major cell type involved in proliferative lesions. Studies using a precursor of DNA, namely [3H] thymidine, and autoradiography have shown that proliferation of SMC is an important and early response to atherogenic stimuli, such as cholesterol feeding, surgically induced hypertension or endothelial injury. Cultures of aortic SMC offer excellent in vitro models to study the reactivity of these cells to recognized or suspected risk factors. Pure SMC cultures are obtained by placing small fragments of aortic media in a defined culture medium and their response evaluated by thymidine incorporation and/or increase in size of the outgrowing cell colony. Factors essential for adequate growth include normal serum constitutents, including the lipoproteins and a platelet derived factor. Replacing the normal serum with dietarily induced hyperlipemic serum results in greatly increased proliferation. The serum fraction largely responsible for this phenomenon is the low density lipoprotein. Simultaneous addition of high density lipoproteins partly suppress this reaction. Serum from diabetic or hypertensive--but normolipemic--animals similarly stimulates these cells to increased proliferation."}
{"id": "PMID:230799", "title": "Adult rhabdomyoma of the larynx.", "content": "A case of rhabdomyoma of the larynx in a 76-year-old woman patient is reported. The tumor was localized on the left vocal cord. This case is, so far described, the seventh one of adult rhadbomyoma of the larynx. The differential histological and histochemical diagnosis with granular cell myoblastoma is discussed and tabulated. Both tumors can easily be confused. In accordance with previously reported cases no evidence of recurrence after more than two years could be observed.", "contents": "Adult rhabdomyoma of the larynx. A case of rhabdomyoma of the larynx in a 76-year-old woman patient is reported. The tumor was localized on the left vocal cord. This case is, so far described, the seventh one of adult rhadbomyoma of the larynx. The differential histological and histochemical diagnosis with granular cell myoblastoma is discussed and tabulated. Both tumors can easily be confused. In accordance with previously reported cases no evidence of recurrence after more than two years could be observed."}
{"id": "PMID:230801", "title": "Marek's disease in chickens: correlation of Marek's disease with nuclear-inclusion formation in feather-follicle epithelium.", "content": "The dynamics of nuclear-inclusion (NI) formation in feather-follicle epithelium of chickens inoculated with Marek's disease virus (with or without prior immunization with turkey herpesvirus) could be divided into two patterns: 1) transient NI formation at the initial stage postchallenge; and 2) persistent NI formation. Incidence of Marek's disease was closely correlated with the dynamics of NI formation. Active NI formation recurred in chickens showing pattern 2 and was closely related to the incidence of nerve lesions.", "contents": "Marek's disease in chickens: correlation of Marek's disease with nuclear-inclusion formation in feather-follicle epithelium. The dynamics of nuclear-inclusion (NI) formation in feather-follicle epithelium of chickens inoculated with Marek's disease virus (with or without prior immunization with turkey herpesvirus) could be divided into two patterns: 1) transient NI formation at the initial stage postchallenge; and 2) persistent NI formation. Incidence of Marek's disease was closely correlated with the dynamics of NI formation. Active NI formation recurred in chickens showing pattern 2 and was closely related to the incidence of nerve lesions."}
{"id": "PMID:230802", "title": "Pathogenicity for baby chicks of the G-4260 strain of the picornavirus \"avian nephritis virus\".", "content": "The pathogenicity of the G-4260 strain of picornavirus for day-old chicks was studied by intraperitoneal inoculation. No clinical signs were observed. A mild yellowish-tan discoloration of the kidneys was noticed in necropsy 7 to 21 days after inoculation. Mean body weight was significantly lower (P less than 0.01) in inoculated groups than in control groups 7 days after inoculation. In a chronological study on the distribution of the virus in organs, the virus was recovered from various organs, exclusive of the brain and trachea. The virus titer was higher in the kidneys, jejunum, rectum, and bursa of Fabricius than in any other organ. Fluorescent antigens were seen predominantly in the epithelia of the renal tubules.", "contents": "Pathogenicity for baby chicks of the G-4260 strain of the picornavirus \"avian nephritis virus\". The pathogenicity of the G-4260 strain of picornavirus for day-old chicks was studied by intraperitoneal inoculation. No clinical signs were observed. A mild yellowish-tan discoloration of the kidneys was noticed in necropsy 7 to 21 days after inoculation. Mean body weight was significantly lower (P less than 0.01) in inoculated groups than in control groups 7 days after inoculation. In a chronological study on the distribution of the virus in organs, the virus was recovered from various organs, exclusive of the brain and trachea. The virus titer was higher in the kidneys, jejunum, rectum, and bursa of Fabricius than in any other organ. Fluorescent antigens were seen predominantly in the epithelia of the renal tubules."}
{"id": "PMID:230803", "title": "Pathological changes in chicks inoculated with the picornavirus \"avian nephritis virus\".", "content": "One-day-old chicks were inoculated intraperitoneally with a newly isolated picornavirus. The inoculated chicks showed no clinical signs until 28 days postinoculation (PI), but discoloration of the kidneys was recognized from 7 to 21 days PI at autopsy. Histologically, focal lesions were observed in the cortex of the kidneys from 3 to 21 days PI. The lesions were characterized by interstitial lymphocytic infiltration and degeneration of epithelial cells of the proximal convoluted tubules. The degenerated cells contained acidophilic granules in their cytoplasm. Electron-microscope examination of the cytoplasm revealed electron-dense amorphous areas, phagosomal areas with viral particles, and isolated crystal arrays of the virus particles, 23 to 30 nm in size. Granular antigen was also detected by fluorescent-antibody technique in the cells.", "contents": "Pathological changes in chicks inoculated with the picornavirus \"avian nephritis virus\". One-day-old chicks were inoculated intraperitoneally with a newly isolated picornavirus. The inoculated chicks showed no clinical signs until 28 days postinoculation (PI), but discoloration of the kidneys was recognized from 7 to 21 days PI at autopsy. Histologically, focal lesions were observed in the cortex of the kidneys from 3 to 21 days PI. The lesions were characterized by interstitial lymphocytic infiltration and degeneration of epithelial cells of the proximal convoluted tubules. The degenerated cells contained acidophilic granules in their cytoplasm. Electron-microscope examination of the cytoplasm revealed electron-dense amorphous areas, phagosomal areas with viral particles, and isolated crystal arrays of the virus particles, 23 to 30 nm in size. Granular antigen was also detected by fluorescent-antibody technique in the cells."}
{"id": "PMID:230804", "title": "Experimental infection of broiler and Leghorn chickens with virulent and avirulent isolates of hemorrhagic enteritis virus.", "content": "The effects of virulent and avirulent isolates of hemorrhagic enteritis virus were studied in Leghorn and broiler chickens. The viruses caused subclinical infections in both strains of birds. The avirulent isolate produced enlarged spleens, inclusion bodies, and antibody in all inoculated Leghorns. In broilers the avirulent virus produced infection in only half of the inoculated birds. Inclusion bodies were widely dispersed in the spleens of both types of birds. The virulent virus produced infection in all inoculated birds of both strains. Inclusion bodies were numerous in the spleens of Leghorn birds and were widely scattered in the spleens of broilers.", "contents": "Experimental infection of broiler and Leghorn chickens with virulent and avirulent isolates of hemorrhagic enteritis virus. The effects of virulent and avirulent isolates of hemorrhagic enteritis virus were studied in Leghorn and broiler chickens. The viruses caused subclinical infections in both strains of birds. The avirulent isolate produced enlarged spleens, inclusion bodies, and antibody in all inoculated Leghorns. In broilers the avirulent virus produced infection in only half of the inoculated birds. Inclusion bodies were widely dispersed in the spleens of both types of birds. The virulent virus produced infection in all inoculated birds of both strains. Inclusion bodies were numerous in the spleens of Leghorn birds and were widely scattered in the spleens of broilers."}
{"id": "PMID:230805", "title": "Studies on interferon induction by infectious bursal disease virus (IBDV). II. Interferon production in White Leghorn chickens infected with an attenuated or pathogenic isolant of IBDV.", "content": "Infectious bursal disease virus (IBDV) isolants that differed in virulence for chickens, were compared as to: 1) induction of interferon in serum and tissues; and 2) stimulation of IBDV serum antibody. Specific-pathogen-free chickens were infected at one day and four weeks of age by the subcutaneous and intranasal routes of inoculation. The pathogenic isolant induced a more generalized interferon response than the attenuated isolant, independent of age or route of inoculation. Pathogenic IBDV stimulated interferon in serum, kidney, lung, thymus, spleen, and bursa of Fabricius. The attenuated virus induced interferon only in the bursa. The serum interferon response was greater following inoculation with pathogenic IBDV than with the attenuated virus. Serum interferon titers peaked 2-3 1/2 days after inoculation. The pathogenic and attenuated viruses stimulated similar IBDV-neutralizing antibody responses, which occurred after peak serum interferon activity.", "contents": "Studies on interferon induction by infectious bursal disease virus (IBDV). II. Interferon production in White Leghorn chickens infected with an attenuated or pathogenic isolant of IBDV. Infectious bursal disease virus (IBDV) isolants that differed in virulence for chickens, were compared as to: 1) induction of interferon in serum and tissues; and 2) stimulation of IBDV serum antibody. Specific-pathogen-free chickens were infected at one day and four weeks of age by the subcutaneous and intranasal routes of inoculation. The pathogenic isolant induced a more generalized interferon response than the attenuated isolant, independent of age or route of inoculation. Pathogenic IBDV stimulated interferon in serum, kidney, lung, thymus, spleen, and bursa of Fabricius. The attenuated virus induced interferon only in the bursa. The serum interferon response was greater following inoculation with pathogenic IBDV than with the attenuated virus. Serum interferon titers peaked 2-3 1/2 days after inoculation. The pathogenic and attenuated viruses stimulated similar IBDV-neutralizing antibody responses, which occurred after peak serum interferon activity."}
{"id": "PMID:230806", "title": "Low incidence of lymphoid tumors in chickens continuously producing endogenous virus.", "content": "A flock of 258 male and 243 female chickens of a cross of Regional Poultry Research Laboratory lines 15B and 7(2) were kept in a filtered-air positive-pressure house and observed for tumors from 100 to more than 729 days of age. These birds produced high titers of a subgroup E endogenous virus from the middle of the embryonic incubation period through the end of the experiment. No neoplasms were observed in the males. The females had two neoplasms indistinguishable from lymphoid leukosis and three other neoplasms not involving lymphoid cells. No evidence was found of infection with exogenous lymphoid leukosis viruses, Marek's disease virus, reticuloendotheliosis virus, or adenovirus (isolated on the isolation farm). Inoculation of another sample of this cross with a lymphoid leukosis virus of subgroup A resulted in 88% mortality with neoplasms (mostly lymphoid leukosis) by 167 days of age. The conclusion is that high levels of spontaneously produced endogenous virus do not induce high levels of neoplasms in chickens susceptible to lymphoid leukosis.", "contents": "Low incidence of lymphoid tumors in chickens continuously producing endogenous virus. A flock of 258 male and 243 female chickens of a cross of Regional Poultry Research Laboratory lines 15B and 7(2) were kept in a filtered-air positive-pressure house and observed for tumors from 100 to more than 729 days of age. These birds produced high titers of a subgroup E endogenous virus from the middle of the embryonic incubation period through the end of the experiment. No neoplasms were observed in the males. The females had two neoplasms indistinguishable from lymphoid leukosis and three other neoplasms not involving lymphoid cells. No evidence was found of infection with exogenous lymphoid leukosis viruses, Marek's disease virus, reticuloendotheliosis virus, or adenovirus (isolated on the isolation farm). Inoculation of another sample of this cross with a lymphoid leukosis virus of subgroup A resulted in 88% mortality with neoplasms (mostly lymphoid leukosis) by 167 days of age. The conclusion is that high levels of spontaneously produced endogenous virus do not induce high levels of neoplasms in chickens susceptible to lymphoid leukosis."}
{"id": "PMID:230807", "title": "An evaluation of methods for eradication of avian leukosis virus from a commercial breeder flock.", "content": "Two trials were conducted to determine whether lymphoid leukosis virus (LLV) could be eradicated from chicken breeder stocks in one generation. Dams were selected as potentially virus-free parents on the basis of negative tests for virus in progeny embryos (trial 1) or in vaginal-cloacal swabs (VCS) (trial 2) of the dams. In trial 1, 8 of 12 groups of chickens hatched from selected breeders remained free of LLV infection through 36 weeks of life. In trial 2, VCS appeared to be more efficient in detecting possible shedder dams, and only 1 of 72 groups of chickens showed evidence of infection at 14 weeks after hatching. Within that positive group, a single chicken was shown to be the possible cause of the infection. The results show that eradication of LLV can be accomplished in one generation by: 1) virological examination of dams for shedding; 2) elimination of the shedder dams; and 3) small-group rearing of the progeny chicks.", "contents": "An evaluation of methods for eradication of avian leukosis virus from a commercial breeder flock. Two trials were conducted to determine whether lymphoid leukosis virus (LLV) could be eradicated from chicken breeder stocks in one generation. Dams were selected as potentially virus-free parents on the basis of negative tests for virus in progeny embryos (trial 1) or in vaginal-cloacal swabs (VCS) (trial 2) of the dams. In trial 1, 8 of 12 groups of chickens hatched from selected breeders remained free of LLV infection through 36 weeks of life. In trial 2, VCS appeared to be more efficient in detecting possible shedder dams, and only 1 of 72 groups of chickens showed evidence of infection at 14 weeks after hatching. Within that positive group, a single chicken was shown to be the possible cause of the infection. The results show that eradication of LLV can be accomplished in one generation by: 1) virological examination of dams for shedding; 2) elimination of the shedder dams; and 3) small-group rearing of the progeny chicks."}
{"id": "PMID:230808", "title": "An enzyme-linked immunosorbent assay for detecting avian leukosis-sarcoma viruses.", "content": "Immunoglobulins from antiserum raised against chromatographically purified avian myeloblastosis virus (AMV) group-specific (gs) antigens were used in enzyme-linked immunosorbent assay (ELISA). Readily discernible color was produced with 2--3 ng of AMV protein in microplate wells coated with 4 micrograms of salt-precipitated immunoglobulins. When a biological assay, i.e., phenotypic mixing (PM), was the criterion for the infectious status of specimens, the ELISA consistently identified a greater percentage of virus-positive specimens than direct complement-fixation (DCF) tests. Over 95% concordance was obtained between the ELISA and PM bioassays when meconia and whole-blood samples were tested. Moreover, three DCF(-) egg albumens from one virus shedder hen were positive by the direct ELISA. Complete agreement was found between a biological assay for endogenous virus and the ELISA when blood and albumens from inbred chickens were tested. The ELISA is a rapid and convenient alternative to the DCF test for identifying infected chickens in eradication programs, because virus-rich sources such as meconia and blood that are unsuitable for DCF can be tested directly.", "contents": "An enzyme-linked immunosorbent assay for detecting avian leukosis-sarcoma viruses. Immunoglobulins from antiserum raised against chromatographically purified avian myeloblastosis virus (AMV) group-specific (gs) antigens were used in enzyme-linked immunosorbent assay (ELISA). Readily discernible color was produced with 2--3 ng of AMV protein in microplate wells coated with 4 micrograms of salt-precipitated immunoglobulins. When a biological assay, i.e., phenotypic mixing (PM), was the criterion for the infectious status of specimens, the ELISA consistently identified a greater percentage of virus-positive specimens than direct complement-fixation (DCF) tests. Over 95% concordance was obtained between the ELISA and PM bioassays when meconia and whole-blood samples were tested. Moreover, three DCF(-) egg albumens from one virus shedder hen were positive by the direct ELISA. Complete agreement was found between a biological assay for endogenous virus and the ELISA when blood and albumens from inbred chickens were tested. The ELISA is a rapid and convenient alternative to the DCF test for identifying infected chickens in eradication programs, because virus-rich sources such as meconia and blood that are unsuitable for DCF can be tested directly."}
{"id": "PMID:230812", "title": "A clinicopathologic study on patients suffering from \"chronic dysentery\".", "content": "Fifty adult patients with the self diagnosis of \"chronic dysentery\" were studied. Their faeces were examined microscopically; they were sigmoidoscoped and their rectal mucosa were examined histologically. Most of them had irritable bowel syndrome. Their sigmoidoscopic appearances were normal and the histology showed only mild increase in the numbers of round cells in the lamina propria. This was regarded as normal for the local population. Ten patients showed cysts of Entamoeba histolytica in the faeces. This was thought to be unrelated to the symptoms. Only four patients had sigmoidoscopic as well as histologic evidence of moderate to severe proctocolitis. One of them was proven to be a case of amoebic colitis. These findings have been discussed.", "contents": "A clinicopathologic study on patients suffering from \"chronic dysentery\". Fifty adult patients with the self diagnosis of \"chronic dysentery\" were studied. Their faeces were examined microscopically; they were sigmoidoscoped and their rectal mucosa were examined histologically. Most of them had irritable bowel syndrome. Their sigmoidoscopic appearances were normal and the histology showed only mild increase in the numbers of round cells in the lamina propria. This was regarded as normal for the local population. Ten patients showed cysts of Entamoeba histolytica in the faeces. This was thought to be unrelated to the symptoms. Only four patients had sigmoidoscopic as well as histologic evidence of moderate to severe proctocolitis. One of them was proven to be a case of amoebic colitis. These findings have been discussed."}
{"id": "PMID:230809", "title": "In vitro isolation, propagation, and characterization of duck hepatitis virus type III.", "content": "The in vitro isolation, propagation, and characterization of duck hepatitis virus Type III (DHV-III), is described. This virus, which is serologically distinct from the classical (Type I) DHV, replicated in liver and kidney cell cultures of duck origin. Replication was limited in chicken and quail kidney and duck embryo fibroblast cultures. It did not replicate in a variety of other cell cultures of avian or mammalian origin. The virus was grown successfully in embryonating eggs of ducks, but not of chickens. DHV-III passed through a 50-nm membrane filter, was stable at pH 3.0 and resisted treatment with 5% chloroform. Virus growth was not inhibited by treatment with 5-iodo-2-deoxyuridine. Electron-microscope examination revealed crystalline arrays in the cytoplasm; virus particles had cubic symmetry, and were about 30 nm in diameter. By these properties, this virus can be classified as a member of the picornavirus group.", "contents": "In vitro isolation, propagation, and characterization of duck hepatitis virus type III. The in vitro isolation, propagation, and characterization of duck hepatitis virus Type III (DHV-III), is described. This virus, which is serologically distinct from the classical (Type I) DHV, replicated in liver and kidney cell cultures of duck origin. Replication was limited in chicken and quail kidney and duck embryo fibroblast cultures. It did not replicate in a variety of other cell cultures of avian or mammalian origin. The virus was grown successfully in embryonating eggs of ducks, but not of chickens. DHV-III passed through a 50-nm membrane filter, was stable at pH 3.0 and resisted treatment with 5% chloroform. Virus growth was not inhibited by treatment with 5-iodo-2-deoxyuridine. Electron-microscope examination revealed crystalline arrays in the cytoplasm; virus particles had cubic symmetry, and were about 30 nm in diameter. By these properties, this virus can be classified as a member of the picornavirus group."}
{"id": "PMID:230810", "title": "Occurrence of atypical fowlpox in poultry farms in Kenya.", "content": "Atypical fowlpox occurred in several poultry farms in Kenya. On two occasions layers had their eyes closed and egg production dropped. Fowlpox virus was isolated from lesions on the inner surfaces of the closed eyelids. Other chickens had lesions covered by yellow caseous necrotic material in the mouth, around the epiglottis, and in the trachea and choanae. Typical proliferative cutaneous lesions were observed in birds of all ages in other flocks examined. Fowlpox virus was recovered from both cutaneous and diphtheritic lesions. The infected chorioallantoic membranes had focal hyperplastic lesions containing pink-staining intracytoplasmic inclusion bodies in most cells. Transmission studies showed that the virus was highly virulent to susceptible chickens.", "contents": "Occurrence of atypical fowlpox in poultry farms in Kenya. Atypical fowlpox occurred in several poultry farms in Kenya. On two occasions layers had their eyes closed and egg production dropped. Fowlpox virus was isolated from lesions on the inner surfaces of the closed eyelids. Other chickens had lesions covered by yellow caseous necrotic material in the mouth, around the epiglottis, and in the trachea and choanae. Typical proliferative cutaneous lesions were observed in birds of all ages in other flocks examined. Fowlpox virus was recovered from both cutaneous and diphtheritic lesions. The infected chorioallantoic membranes had focal hyperplastic lesions containing pink-staining intracytoplasmic inclusion bodies in most cells. Transmission studies showed that the virus was highly virulent to susceptible chickens."}
{"id": "PMID:230815", "title": "A typology of the gnathostome adenohypophysis with some emphasis on its gonadotropic function.", "content": "Recent publications show that the average gnathostome adenohypophysis consists of four parts and contains six morphological cell types. Histophysiological and immunocytochemical data prove the secretion of one or two gonadotropins by one type of basophils that in numerous species in characterized by the presence of large globules besides secretory vesicles. The existence of a second type of gonadotropin secreting cells remains doubtful. Thyrotropin is produced by a separate type of basophilic cells, prolactin by erythrosinophils of the rostral pars distalis, and somatotropin by orangeophils of the proximal pars distalis. At rostral and caudal places of contact with the neurohypophysis, cells are concentrated that may be lead-haematoxylin-positive, and produce a protein consisting of peptides with hormonal and opiate activities. Among the hormones secreted by these cells, situated in the pars distalis and the pars intermedia, are corticotropin and melanotropin respectively. The factors that cause the differentiation of the primordium of the adenohypophysis are almost entirely unknown.", "contents": "A typology of the gnathostome adenohypophysis with some emphasis on its gonadotropic function. Recent publications show that the average gnathostome adenohypophysis consists of four parts and contains six morphological cell types. Histophysiological and immunocytochemical data prove the secretion of one or two gonadotropins by one type of basophils that in numerous species in characterized by the presence of large globules besides secretory vesicles. The existence of a second type of gonadotropin secreting cells remains doubtful. Thyrotropin is produced by a separate type of basophilic cells, prolactin by erythrosinophils of the rostral pars distalis, and somatotropin by orangeophils of the proximal pars distalis. At rostral and caudal places of contact with the neurohypophysis, cells are concentrated that may be lead-haematoxylin-positive, and produce a protein consisting of peptides with hormonal and opiate activities. Among the hormones secreted by these cells, situated in the pars distalis and the pars intermedia, are corticotropin and melanotropin respectively. The factors that cause the differentiation of the primordium of the adenohypophysis are almost entirely unknown."}
{"id": "PMID:230811", "title": "Isolation of Pacheco's disease herpesvirus in Texas.", "content": "Pacheco's disease herpesvirus was determined to be the agent responsible for the death of about 200 psittacine birds comprising five species. Clinical signs, necropsy lesions, and virus isolation and identification methods are described.", "contents": "Isolation of Pacheco's disease herpesvirus in Texas. Pacheco's disease herpesvirus was determined to be the agent responsible for the death of about 200 psittacine birds comprising five species. Clinical signs, necropsy lesions, and virus isolation and identification methods are described."}
{"id": "PMID:230818", "title": "The nature of the hydroxyapatite-binding site in salivary acidic proline-rich proteins.", "content": "Protein A and C, which are major components of the acidic proline-rich proteins in human saliva, were digested, before or after adsorption to hydroxyapatite, with alkaline phosphatase, trypsin, thermolysin and  a proteinase preparation from salivary sediment. The results demonstrate that the binding site is located in the proline-poor N-terminal part of the protein, possibly between residues 3 and 25. Phosphoserine is necessary for maximal adsorption of the proteins to hydroxyapatite. When proteins A and C are adsorbed to hydroxyapatite before proteolytic digestion there is a protection of some of the susceptible bonds in the N-terminal part of the proteins and a gradual removal of the proline-rich C-terminal part. Thermolysin can cleave susceptible bonds in the part of the protein that remains bound to hydroxyapatite, but at least some of the resulting peptides are retained on the mineral. Since the ability of the proteins to inhibit hydroxyapatite formation and to bind calcium is located in the N-terminal proline-poor part, it is possible that these activities are retained after proteolytic digestion of the adsorbed proteins.", "contents": "The nature of the hydroxyapatite-binding site in salivary acidic proline-rich proteins. Protein A and C, which are major components of the acidic proline-rich proteins in human saliva, were digested, before or after adsorption to hydroxyapatite, with alkaline phosphatase, trypsin, thermolysin and  a proteinase preparation from salivary sediment. The results demonstrate that the binding site is located in the proline-poor N-terminal part of the protein, possibly between residues 3 and 25. Phosphoserine is necessary for maximal adsorption of the proteins to hydroxyapatite. When proteins A and C are adsorbed to hydroxyapatite before proteolytic digestion there is a protection of some of the susceptible bonds in the N-terminal part of the proteins and a gradual removal of the proline-rich C-terminal part. Thermolysin can cleave susceptible bonds in the part of the protein that remains bound to hydroxyapatite, but at least some of the resulting peptides are retained on the mineral. Since the ability of the proteins to inhibit hydroxyapatite formation and to bind calcium is located in the N-terminal proline-poor part, it is possible that these activities are retained after proteolytic digestion of the adsorbed proteins."}
{"id": "PMID:230819", "title": "Isolation and partial characterization of high-density lipoprotein HDL1 from rat plasma by gradient centrifugation.", "content": "The lipoproteins isolated from rat plasma by flotation in the density range 1.019-1.063 g/ml were further characterized. Using rate zonal ultracentrifugation, we isolated two lipoproteins in almost equal proportions from this density range. Similar isolations may be accomplished with density gradients in a swinging-bucket rotor. On isopycnic-density-gradient ultracentrifugation one component banded at rho = 1.031 g/ml and the other at rho = 1.054 g/ml. More that 98% of the apoprotein of the lighter component was B protein, and hence this particle is LD (low-density) lipoprotein. Of the apoproteins of the rho = 1.054 g/ml particles, designated lipoprotein HDL1, over 60% was arginine-rich peptide, and the remainder was A-I, A-IV and C peptides. The molecular weight of these lipoproteins determined by agarose column chromatography was 2.36 x 10(6) for LD lipoprotein and 1.30 x 10(6) for lipoprotein HDL1. On electron microscopy the radius of LD lipoprotein was 14.0 nm and that of lipoprotein HDL1 was 10.0 nm, in contrast with molecular radii of 10.4 nm and 8.4 nm respectively determined from the gel-permeation-chromatography data. The lipid and phospholipid composition of both particles was determined. Lipoprotein HDL1 was notable for both the concentration of its esterified cholesterol, which was similar to that of LD lipoprotein, and the low triacylglycerol content, resembling that of HD lipoprotein. The possible origin of lipoprotein HDL1 is discussed.", "contents": "Isolation and partial characterization of high-density lipoprotein HDL1 from rat plasma by gradient centrifugation. The lipoproteins isolated from rat plasma by flotation in the density range 1.019-1.063 g/ml were further characterized. Using rate zonal ultracentrifugation, we isolated two lipoproteins in almost equal proportions from this density range. Similar isolations may be accomplished with density gradients in a swinging-bucket rotor. On isopycnic-density-gradient ultracentrifugation one component banded at rho = 1.031 g/ml and the other at rho = 1.054 g/ml. More that 98% of the apoprotein of the lighter component was B protein, and hence this particle is LD (low-density) lipoprotein. Of the apoproteins of the rho = 1.054 g/ml particles, designated lipoprotein HDL1, over 60% was arginine-rich peptide, and the remainder was A-I, A-IV and C peptides. The molecular weight of these lipoproteins determined by agarose column chromatography was 2.36 x 10(6) for LD lipoprotein and 1.30 x 10(6) for lipoprotein HDL1. On electron microscopy the radius of LD lipoprotein was 14.0 nm and that of lipoprotein HDL1 was 10.0 nm, in contrast with molecular radii of 10.4 nm and 8.4 nm respectively determined from the gel-permeation-chromatography data. The lipid and phospholipid composition of both particles was determined. Lipoprotein HDL1 was notable for both the concentration of its esterified cholesterol, which was similar to that of LD lipoprotein, and the low triacylglycerol content, resembling that of HD lipoprotein. The possible origin of lipoprotein HDL1 is discussed."}
{"id": "PMID:230817", "title": "Synthesis and degradation of NAD in guinea pig cardiac muscle: I. Dependence upon the extracellular concentration of nicotinamide and nicotinic acid.", "content": "The NAD concentration as well as the 14C-incorporation in NAD and the disappearance of 14C-NAD were studied in spontaneously beating atria of guinea pigs at high and low concentrations of the precursors nicotinamide or nicotinic acid. Atria were incubated in Krebs-Henseleit solution containing 15 mM glucose and the appropriate precursors at 30 degrees C. The control NAD concentration (33 nMol/100 mg w.w.) remained unchanged during a 24-h-incubation time. -20 mM 14C-nicotinamide increased the total NAD about three-fold (90 nMol/100 mg w.w.) after an incubation period of 24 h, with positive effects on the performance. The incorporation rate in 14C-NAD was calculated to be 43.7 nMol/100 mg w.w. . 24 h. The ADPR moiety for the NAD synthesis stemmed from an endogenous pool. Between 5 and 20 mM nicotinamide the increase in the NAD concentration followed an apparent Michaelis-Menten kinetics with a Km of 6.1 mM nicotinamide and a Vmax of 70.92 nMol NAD/100 mg w.w. . 24 h. This can be explained as a new synthesis of NAD by a high concentration of nictoinamide and also by a decreased degradation of NAD, due to inhibition of the glycohydrolase by the high concentration of nicotinamide. The ratio of incorporation and disappearance of 14C-NAD during the 8th and 16th h incubation period was 2:1. After pre-incubation with 20 mM nicotinamide for an 8-h period the NAD concentration decreased to normal values after incubation for 8 h in a nicotinamide free medium. -20 mM 14C-nicotinic acid did not change the total NAD level and no significant incorporation in 14C-NAD could be detected, whereas negative effects on the performance occurred. -10 muM 14C-nicotinamide showed a slight increase in the total NAD concentration (39.7 nMol/100 mg w.w.) and in the 14C-incorporation (4.8 nMol/100 mg w.w.) within 24 h. -10 muM 14C-nicotinic acid seemed here to be the better precursor in this concentration. The NAD concentration increased to 49.8 nMol/100 mg w.w. after a 16 h incubation period and the incorporation in 14C-NAD was 12.1 nMol/100 mg w.w. after an incubation time of 24 h. As consequences of the observed different influences of each precursor on NAD turnover and NAD concentration the pathways of NAD synthesis and degradation must be studied. The importance of an increased NAD level for the energy metabolism of the cardiac muscle under aerobic and anaerobic conditions is discussed.", "contents": "Synthesis and degradation of NAD in guinea pig cardiac muscle: I. Dependence upon the extracellular concentration of nicotinamide and nicotinic acid. The NAD concentration as well as the 14C-incorporation in NAD and the disappearance of 14C-NAD were studied in spontaneously beating atria of guinea pigs at high and low concentrations of the precursors nicotinamide or nicotinic acid. Atria were incubated in Krebs-Henseleit solution containing 15 mM glucose and the appropriate precursors at 30 degrees C. The control NAD concentration (33 nMol/100 mg w.w.) remained unchanged during a 24-h-incubation time. -20 mM 14C-nicotinamide increased the total NAD about three-fold (90 nMol/100 mg w.w.) after an incubation period of 24 h, with positive effects on the performance. The incorporation rate in 14C-NAD was calculated to be 43.7 nMol/100 mg w.w. . 24 h. The ADPR moiety for the NAD synthesis stemmed from an endogenous pool. Between 5 and 20 mM nicotinamide the increase in the NAD concentration followed an apparent Michaelis-Menten kinetics with a Km of 6.1 mM nicotinamide and a Vmax of 70.92 nMol NAD/100 mg w.w. . 24 h. This can be explained as a new synthesis of NAD by a high concentration of nictoinamide and also by a decreased degradation of NAD, due to inhibition of the glycohydrolase by the high concentration of nicotinamide. The ratio of incorporation and disappearance of 14C-NAD during the 8th and 16th h incubation period was 2:1. After pre-incubation with 20 mM nicotinamide for an 8-h period the NAD concentration decreased to normal values after incubation for 8 h in a nicotinamide free medium. -20 mM 14C-nicotinic acid did not change the total NAD level and no significant incorporation in 14C-NAD could be detected, whereas negative effects on the performance occurred. -10 muM 14C-nicotinamide showed a slight increase in the total NAD concentration (39.7 nMol/100 mg w.w.) and in the 14C-incorporation (4.8 nMol/100 mg w.w.) within 24 h. -10 muM 14C-nicotinic acid seemed here to be the better precursor in this concentration. The NAD concentration increased to 49.8 nMol/100 mg w.w. after a 16 h incubation period and the incorporation in 14C-NAD was 12.1 nMol/100 mg w.w. after an incubation time of 24 h. As consequences of the observed different influences of each precursor on NAD turnover and NAD concentration the pathways of NAD synthesis and degradation must be studied. The importance of an increased NAD level for the energy metabolism of the cardiac muscle under aerobic and anaerobic conditions is discussed."}
{"id": "PMID:230820", "title": "Abnormal blood-group-Ss-active sialoglycoproteins in the membrane of Miltenberger class III, IV and V human erythrocytes.", "content": "1. We have studied the inherited changes occurring in the sialoglycoproteins of membranes from erythrocytes of type Miltenberger Class III (Mi.III), Miltenberger Class IV (Mi.IV) and Miltenberger Class V (Mi.V) by using sodium dodecyl sulphate/polyacrylamide gel electrophoresis and lactoperoxidase radioiodination. 2. Mi.III erythrocytes lack the normal blood-group-Ss-active sialoglycoprotein but contain an unusual s-active sialoglycoprotein of higher apparent molecular weight. A similar abnormal S-active sialoglycoprotein appears to occur in Mi.IV erythrocytes. 3. The Mi.V condition is associated with the hemizygous absence of both the normal blood-group-MN-active sialoglycoprotein and the normal Ss-active sialoglycorprotein. However, a new sialoglycoprotein component is present in these cells that has properties characteristic of both the MN-active and Ss-active sialoglycoproteins. 4. Our results suggest that the new sialoglycorportein present in Mi.V erythrocytes is a hybrid of the normal MN sialoglycoprotein and an s-active sialoglycoprotein that has properties similar to the s-active sialoglycoprotein found in Mi.III erythrocytes. We suggest that the unusual Mi.V sialoglycoprotein is derived from chromosomal misalignment with unequal crossing-over between the genes for the MN- and Ss-active sialoglycoproteins in a manner similar to that which gives rise to haemoglobin Lepore. 5. Further studies of S-s-erythrocytes confirm that these cells lack normal Ss-active sialoglycoprotein, but contain an unusual component that shows some of the properties of the normal Ss-active sialoglycoprotein. 6. Analysis of erythrocytes of type Mk/Mi.III confirms that, in addition to the known hemizygous lack of the MN-active sialoglycoprotein, the Mk condition is also associated with a loss of the Ss-active sialoglycoprotein. 7. In order to facilitate discussion of the complex changes that occur in these variant erythrocytes, a new unified nomenclature is used for the erythrocyte sialoglycoproteins.", "contents": "Abnormal blood-group-Ss-active sialoglycoproteins in the membrane of Miltenberger class III, IV and V human erythrocytes. 1. We have studied the inherited changes occurring in the sialoglycoproteins of membranes from erythrocytes of type Miltenberger Class III (Mi.III), Miltenberger Class IV (Mi.IV) and Miltenberger Class V (Mi.V) by using sodium dodecyl sulphate/polyacrylamide gel electrophoresis and lactoperoxidase radioiodination. 2. Mi.III erythrocytes lack the normal blood-group-Ss-active sialoglycoprotein but contain an unusual s-active sialoglycoprotein of higher apparent molecular weight. A similar abnormal S-active sialoglycoprotein appears to occur in Mi.IV erythrocytes. 3. The Mi.V condition is associated with the hemizygous absence of both the normal blood-group-MN-active sialoglycoprotein and the normal Ss-active sialoglycorprotein. However, a new sialoglycoprotein component is present in these cells that has properties characteristic of both the MN-active and Ss-active sialoglycoproteins. 4. Our results suggest that the new sialoglycorportein present in Mi.V erythrocytes is a hybrid of the normal MN sialoglycoprotein and an s-active sialoglycoprotein that has properties similar to the s-active sialoglycoprotein found in Mi.III erythrocytes. We suggest that the unusual Mi.V sialoglycoprotein is derived from chromosomal misalignment with unequal crossing-over between the genes for the MN- and Ss-active sialoglycoproteins in a manner similar to that which gives rise to haemoglobin Lepore. 5. Further studies of S-s-erythrocytes confirm that these cells lack normal Ss-active sialoglycoprotein, but contain an unusual component that shows some of the properties of the normal Ss-active sialoglycoprotein. 6. Analysis of erythrocytes of type Mk/Mi.III confirms that, in addition to the known hemizygous lack of the MN-active sialoglycoprotein, the Mk condition is also associated with a loss of the Ss-active sialoglycoprotein. 7. In order to facilitate discussion of the complex changes that occur in these variant erythrocytes, a new unified nomenclature is used for the erythrocyte sialoglycoproteins."}
{"id": "PMID:230821", "title": "Partial purification and characterization of chick-embryo prolyl 3-hydroxylase.", "content": "Prolyl 3-hydroxylase was purified up to about 5000-fold from an (NH4)2SO4 fraction of chick-embryo extract by a procedure consisting of affinity chromatography on denatured collagen linked to agarose, elution with ethylene glycol and gel filtration. The molecular weight of the purified enzyme is about 160000 by gel filtration The enzyme is probably a glycoprotein, since (a) its activity is inhibited by concanavalin A, and (b) the enzyme is bound to columns of this lectin coupled to agarose and can be eluted with a buffer containing methyl alpha-D-mannoside. The Km values for Fe2+, 2-oxoglutarate, O2 and ascorbate in the prolyl 3-hydroxylase reaction were found to be very similar to those previously reported for these co-substrates in the prolyl 4-hydroxylase and lysyl hydroxylase reactions.", "contents": "Partial purification and characterization of chick-embryo prolyl 3-hydroxylase. Prolyl 3-hydroxylase was purified up to about 5000-fold from an (NH4)2SO4 fraction of chick-embryo extract by a procedure consisting of affinity chromatography on denatured collagen linked to agarose, elution with ethylene glycol and gel filtration. The molecular weight of the purified enzyme is about 160000 by gel filtration The enzyme is probably a glycoprotein, since (a) its activity is inhibited by concanavalin A, and (b) the enzyme is bound to columns of this lectin coupled to agarose and can be eluted with a buffer containing methyl alpha-D-mannoside. The Km values for Fe2+, 2-oxoglutarate, O2 and ascorbate in the prolyl 3-hydroxylase reaction were found to be very similar to those previously reported for these co-substrates in the prolyl 4-hydroxylase and lysyl hydroxylase reactions."}
{"id": "PMID:230822", "title": "Spectroscopic forms of carbonmonoxi-cytochrome oxidase.", "content": "A systematic study of the errors of low-temperature recording of kinetics of the cytochrome oxidase-CO reaction had identified the classic devitrification process of Keilin & Hartree [(1950) Nature (London)165, 504-505]. The methodology described here minimizes this effect, and the computation methods afford appropriate ways of detecting a residual effect. Thus it has been possible to identify that absorption difference spectra and kinetics of the reaction of fully reduced or half-reduced cytochrome oxidase with CO indicate only one spectroscopic form of the respective carbonmonoxi-cytochrome oxidase.", "contents": "Spectroscopic forms of carbonmonoxi-cytochrome oxidase. A systematic study of the errors of low-temperature recording of kinetics of the cytochrome oxidase-CO reaction had identified the classic devitrification process of Keilin & Hartree [(1950) Nature (London)165, 504-505]. The methodology described here minimizes this effect, and the computation methods afford appropriate ways of detecting a residual effect. Thus it has been possible to identify that absorption difference spectra and kinetics of the reaction of fully reduced or half-reduced cytochrome oxidase with CO indicate only one spectroscopic form of the respective carbonmonoxi-cytochrome oxidase."}
{"id": "PMID:230823", "title": "Reversal of part of the aldehyde dehydrogenase reaction pathway during the hydrolysis of an ester.", "content": "An aldehyde dehydrogenase from rabbit liver, a homogeneous protein on three distinct polyacrylamide-gel systems, has an associated 4-nitrophenyl esterase activity. At pH 7.0 in the presence of 80 micrometer-NADH and 800 micrometer-4-nitrophenyl acetate the enzyme produces NAD+ and a stoicheiometric amount of an aldehyde, as well as hydrolysing the ester. On this and other evidence it is proposed that ester hydrolysis occurs at the usual active site of the enzyme.", "contents": "Reversal of part of the aldehyde dehydrogenase reaction pathway during the hydrolysis of an ester. An aldehyde dehydrogenase from rabbit liver, a homogeneous protein on three distinct polyacrylamide-gel systems, has an associated 4-nitrophenyl esterase activity. At pH 7.0 in the presence of 80 micrometer-NADH and 800 micrometer-4-nitrophenyl acetate the enzyme produces NAD+ and a stoicheiometric amount of an aldehyde, as well as hydrolysing the ester. On this and other evidence it is proposed that ester hydrolysis occurs at the usual active site of the enzyme."}
{"id": "PMID:230824", "title": "Relationship between activity of hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase and secretion of very-low-density-lipoprotein cholesterol by the isolated perfused liver and in the intact rat.", "content": "The hepatic output of triacylglycerol and cholesterol from very-low-density lipoprotein (VLD lipoprotein), and the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase were compared in the isolated perfused rat-liver preparation and in the intact rat. The output of triacylglycerol and cholesterol from VLD lipoprotein by the perfused liver was stimulated by oleate concomitant with stimulation of hepatic microsomal hydroxymethylglutaryl-coenzyme A reductase activity. In the intact animal treated with Triton WR-1339, the magnitude of secretion of triacylglycerol and cholesterol from VLD lipoprotein coincided with the diurnal rhythm of hepatic hydroxymethylglutaryl-coenzyme A reductase activity, which was maximal at 24:00 h and minimal at 12:00 h. These observations suggest that the stimulation of the reductase and of the secretion of cholesterol from VLD lipoprotein by non-esterified fatty acids, as observed with the isolated perfused rat liver preparation in vitro, may also be an important physiological mechanism in vivo. Hepatic cholesterogenesis may be stimulated under conditions conductive to the secretion of the VLD lipoprotein, the primary transport form for triacylglycerol in the postabsorptive state.", "contents": "Relationship between activity of hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase and secretion of very-low-density-lipoprotein cholesterol by the isolated perfused liver and in the intact rat. The hepatic output of triacylglycerol and cholesterol from very-low-density lipoprotein (VLD lipoprotein), and the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase were compared in the isolated perfused rat-liver preparation and in the intact rat. The output of triacylglycerol and cholesterol from VLD lipoprotein by the perfused liver was stimulated by oleate concomitant with stimulation of hepatic microsomal hydroxymethylglutaryl-coenzyme A reductase activity. In the intact animal treated with Triton WR-1339, the magnitude of secretion of triacylglycerol and cholesterol from VLD lipoprotein coincided with the diurnal rhythm of hepatic hydroxymethylglutaryl-coenzyme A reductase activity, which was maximal at 24:00 h and minimal at 12:00 h. These observations suggest that the stimulation of the reductase and of the secretion of cholesterol from VLD lipoprotein by non-esterified fatty acids, as observed with the isolated perfused rat liver preparation in vitro, may also be an important physiological mechanism in vivo. Hepatic cholesterogenesis may be stimulated under conditions conductive to the secretion of the VLD lipoprotein, the primary transport form for triacylglycerol in the postabsorptive state."}
{"id": "PMID:230825", "title": "Increase in liver nuclear tri-iodothyronine receptors associated with increased deoxyribonucleic acid by long-term administration of tri-iodothyronine in thyroidectomized rats.", "content": "The effect of long-term administration of small amounts of tri-iodothyronine was examined on the nuclear tri-iodothyronine receptors in rat liver. The maximal binding capacity (C(max.)) and association constant (K(a)) of the receptors were determined in thyroidectomized rats given vehicle alone (group A), 2mug of tri-iodothyronine/100g body wt. (group B) or 7mug of tri-iodothyronine/100g body wt. (group C) for 2 weeks. Scatchard analyses with correction for the amount of endogenous tri-iodothyronine revealed that C(max.) values per g of liver were increased to 1.5 and 2.7 times the control value in groups B and C respectively. Since concentrations of DNA per g of liver were significantly increased in the two groups of hormone-treated rats, C(max.) values per mg of DNA were nearly the same in group B, but still increased significantly in group C compared with group A. K(a) values remained unchanged in all three groups of animals. Mitochondrial alpha-glycerophosphate dehydrogenase activity was 9.6 and 28.7 times as high in groups B and C, respectively, as in group A. Concentrations of endogenous tri-iodothyronine bound to non-histone protein were substantially increased in groups B and C, although concentrations of serum tri-iodothyronine remained rather low. The results obtained indicate that the long-term administration of tri-iodothyronine in small doses induces an increase in the nuclear receptors associated with increased DNA with and without accompanying a relative increase in the receptor concentration in thyroidectomized rats. Also the hormonal effect is closely related to the total number of the nuclear receptors and the concentrations of nuclear tri-iodothyronine bound to the receptors rather than the serum tri-iodothyronine concentrations.", "contents": "Increase in liver nuclear tri-iodothyronine receptors associated with increased deoxyribonucleic acid by long-term administration of tri-iodothyronine in thyroidectomized rats. The effect of long-term administration of small amounts of tri-iodothyronine was examined on the nuclear tri-iodothyronine receptors in rat liver. The maximal binding capacity (C(max.)) and association constant (K(a)) of the receptors were determined in thyroidectomized rats given vehicle alone (group A), 2mug of tri-iodothyronine/100g body wt. (group B) or 7mug of tri-iodothyronine/100g body wt. (group C) for 2 weeks. Scatchard analyses with correction for the amount of endogenous tri-iodothyronine revealed that C(max.) values per g of liver were increased to 1.5 and 2.7 times the control value in groups B and C respectively. Since concentrations of DNA per g of liver were significantly increased in the two groups of hormone-treated rats, C(max.) values per mg of DNA were nearly the same in group B, but still increased significantly in group C compared with group A. K(a) values remained unchanged in all three groups of animals. Mitochondrial alpha-glycerophosphate dehydrogenase activity was 9.6 and 28.7 times as high in groups B and C, respectively, as in group A. Concentrations of endogenous tri-iodothyronine bound to non-histone protein were substantially increased in groups B and C, although concentrations of serum tri-iodothyronine remained rather low. The results obtained indicate that the long-term administration of tri-iodothyronine in small doses induces an increase in the nuclear receptors associated with increased DNA with and without accompanying a relative increase in the receptor concentration in thyroidectomized rats. Also the hormonal effect is closely related to the total number of the nuclear receptors and the concentrations of nuclear tri-iodothyronine bound to the receptors rather than the serum tri-iodothyronine concentrations."}
{"id": "PMID:230826", "title": "Metabolism of cholecalciferol in land snails.", "content": "1. Radioactively labelled cholecalciferol was injected into the land snails Levantina hiersolyma and Theba pisana. Three metabolites (C, D and E), more polar than cholecalciferol, were found. 2. Metabolite C was found to be identical with 25-hydroxycholecalciferol. On injection of 25-hydroxy[26,27-3H]cholecalciferol, metabolite E was predominantly formed. Metabolite D was predominantly formed from cholecalciferol. Metabolites D and E differ from any known cholecalciferol metabolites. 3. The intestine was found to be the tissue capable of carrying out the transformation of 25-hydroxycholecalciferol into metabolite E. 4. 25-Hydroxycholecalciferol and metabolite E were localized in the digestive gland of the snail, the tissue responsible for the absorption of Ca2+ and its storage. Metabolite D was not localized in any specific tissue.", "contents": "Metabolism of cholecalciferol in land snails. 1. Radioactively labelled cholecalciferol was injected into the land snails Levantina hiersolyma and Theba pisana. Three metabolites (C, D and E), more polar than cholecalciferol, were found. 2. Metabolite C was found to be identical with 25-hydroxycholecalciferol. On injection of 25-hydroxy[26,27-3H]cholecalciferol, metabolite E was predominantly formed. Metabolite D was predominantly formed from cholecalciferol. Metabolites D and E differ from any known cholecalciferol metabolites. 3. The intestine was found to be the tissue capable of carrying out the transformation of 25-hydroxycholecalciferol into metabolite E. 4. 25-Hydroxycholecalciferol and metabolite E were localized in the digestive gland of the snail, the tissue responsible for the absorption of Ca2+ and its storage. Metabolite D was not localized in any specific tissue."}
{"id": "PMID:230827", "title": "The mechanism of action of lutropin on regulator protein(s) involved in Leydig-cell steroidogenesis.", "content": "The dependence on lutropin of the synthesis of a proposed short-half-life protein regulator involved in Leydig-cell steroidogenesis was investigated. This was carried out by determining the effect of the protein-synthesis inhibitor cycloheximide, added before and during incubations with lutropin (and/or dibutyryl cyclic AMP), on the rate of testosterone production in suspensions of purified Leydig cells from adult rat testes. The Leydig cells were preincubated in Eagle's medium for 2.5h followed by 30min incubation with and without cycloheximide. The inhibitor was removed by washing the cells and then lutropin was added and testosterone concentrations were determined after incubation of the cells at 32 degrees C. No significant effect of cycloheximide pretreatment on lutropin-stimulated steroidogenesis was found during 60min incubation. This was in contrast with the complete inhibiting effect of cycloheximide when it was added with the lutropin. The pretreatment experiments with cycloheximide were repeated in the presence of dibutyryl cyclic AMP and elipten phosphate (to inhibit cholesterol side-chain cleavage) followed by incubation with lutropin. After 5, 10, 20 and 60min of incubation, testosterone concentrations were 61+/-3, 46+/-3, 27+/-4 and 18+/-4% lower than in the cells pretreated without cycloheximide respectively (means+/-s.e.m., n=4-6). In the cells not pretreated with cycloheximide and in the absence of lutropin, testosterone production increased from 1.36+/-0.5 to 36.5+/-1.0ng/10(6) cells during 20min of incubation, after which no further increase occurred. Pretreatment of the cells with cycloheximide decreased these testosterone concentrations by 65, 46, 42 and 36% in the 5, 10, 20 and 60min incubations respectively (mean values, n=2-4). It is apparent from these results that inhibition of steroidogenesis only occurs if protein synthesis is inhibited in the presence of lutropin or cyclic AMP. A new hypothesis is put forward to explain these findings: it is proposed that lutropin affects the stability of a precursor of a regulator protein by converting it from a stable (inactive) to an unstable (active) form with a short half-life.", "contents": "The mechanism of action of lutropin on regulator protein(s) involved in Leydig-cell steroidogenesis. The dependence on lutropin of the synthesis of a proposed short-half-life protein regulator involved in Leydig-cell steroidogenesis was investigated. This was carried out by determining the effect of the protein-synthesis inhibitor cycloheximide, added before and during incubations with lutropin (and/or dibutyryl cyclic AMP), on the rate of testosterone production in suspensions of purified Leydig cells from adult rat testes. The Leydig cells were preincubated in Eagle's medium for 2.5h followed by 30min incubation with and without cycloheximide. The inhibitor was removed by washing the cells and then lutropin was added and testosterone concentrations were determined after incubation of the cells at 32 degrees C. No significant effect of cycloheximide pretreatment on lutropin-stimulated steroidogenesis was found during 60min incubation. This was in contrast with the complete inhibiting effect of cycloheximide when it was added with the lutropin. The pretreatment experiments with cycloheximide were repeated in the presence of dibutyryl cyclic AMP and elipten phosphate (to inhibit cholesterol side-chain cleavage) followed by incubation with lutropin. After 5, 10, 20 and 60min of incubation, testosterone concentrations were 61+/-3, 46+/-3, 27+/-4 and 18+/-4% lower than in the cells pretreated without cycloheximide respectively (means+/-s.e.m., n=4-6). In the cells not pretreated with cycloheximide and in the absence of lutropin, testosterone production increased from 1.36+/-0.5 to 36.5+/-1.0ng/10(6) cells during 20min of incubation, after which no further increase occurred. Pretreatment of the cells with cycloheximide decreased these testosterone concentrations by 65, 46, 42 and 36% in the 5, 10, 20 and 60min incubations respectively (mean values, n=2-4). It is apparent from these results that inhibition of steroidogenesis only occurs if protein synthesis is inhibited in the presence of lutropin or cyclic AMP. A new hypothesis is put forward to explain these findings: it is proposed that lutropin affects the stability of a precursor of a regulator protein by converting it from a stable (inactive) to an unstable (active) form with a short half-life."}
{"id": "PMID:230828", "title": "Inhibition of pulmonary prostaglandin metabolism by exposure of animals to oxygen or nitrogen dioxide.", "content": "The effects of exposure of animals to 100% O2 and NO2 on the rate of prostaglandin metabolism by lung and kidney were studied in vitro. Exposure of guinea pigs to 100% O2 for 48 h inhibited the metabolism of prostaglandin F2 alpha by both NAD+- and NADP+-dependent prostaglandin dehydrogenase in lung, but had no effect on the metabolism in kidney. Succinate dehydrogenase, but not glucose 6-phosphate dehydrogenase, in guinea-pig lung was inhibited by exposure to 100% O2. Exposure to 46 p.p.m. but not 16 or 29 p.p.m. NO2 for 6 h inhibited guinea-pig lung prostaglandin dehydrogenase in vitro. The inhibition of pulmonary prostaglandin dehydrogenase by exposure to 100% O2 or to 49 p.p.m. NO2 was dependent on the duration of exposure, but returned to control values within 7 days after cessation of the exposure. The pulmonary transport system responsible for removing circulating prostaglandins from the blood was not affected by exposure to 100% O2 as measured by using the isolated perfused lung. Kinetic analysis of the inhibition of pulmonary prostaglandin dehydrogenase activity in guinea pig exposed to 100% O2 showed non-competitive inhibition with respect to both prostaglandin F2 alpha and NAD+, which suggests destruction or inactivation of the enzyme. Pulmonary prostaglandin dehydrogenase appears to be inhibited by exposure to oxidant gases, which may lead to elevated prostaglandin concentrations in the lungs or in the systemic circulation.", "contents": "Inhibition of pulmonary prostaglandin metabolism by exposure of animals to oxygen or nitrogen dioxide. The effects of exposure of animals to 100% O2 and NO2 on the rate of prostaglandin metabolism by lung and kidney were studied in vitro. Exposure of guinea pigs to 100% O2 for 48 h inhibited the metabolism of prostaglandin F2 alpha by both NAD+- and NADP+-dependent prostaglandin dehydrogenase in lung, but had no effect on the metabolism in kidney. Succinate dehydrogenase, but not glucose 6-phosphate dehydrogenase, in guinea-pig lung was inhibited by exposure to 100% O2. Exposure to 46 p.p.m. but not 16 or 29 p.p.m. NO2 for 6 h inhibited guinea-pig lung prostaglandin dehydrogenase in vitro. The inhibition of pulmonary prostaglandin dehydrogenase by exposure to 100% O2 or to 49 p.p.m. NO2 was dependent on the duration of exposure, but returned to control values within 7 days after cessation of the exposure. The pulmonary transport system responsible for removing circulating prostaglandins from the blood was not affected by exposure to 100% O2 as measured by using the isolated perfused lung. Kinetic analysis of the inhibition of pulmonary prostaglandin dehydrogenase activity in guinea pig exposed to 100% O2 showed non-competitive inhibition with respect to both prostaglandin F2 alpha and NAD+, which suggests destruction or inactivation of the enzyme. Pulmonary prostaglandin dehydrogenase appears to be inhibited by exposure to oxidant gases, which may lead to elevated prostaglandin concentrations in the lungs or in the systemic circulation."}
{"id": "PMID:230829", "title": "Synthesis of renin substrate by rat liver.", "content": "The present study attempts to determine if the isolated rat liver is capable of synthesizing renin substrate from 14C-labelled amino acids added in the perfusate. The renin substrate is characterized via reaction with renin, forming a substance that is subsequently identified as proangiotensin. Extensive evaluation of the reaction product is carried out by using molecular-sieve chromatography, countercurrent distribution, reactivity with converting enzyme, radioimmunological technique and bioassay. The results demonstrate that isolated rat liver perfused with artificial salt solution is capable of synthesizing a protein that reacts with renin to form a radioactive substance indistinguishable from proangiotensin.", "contents": "Synthesis of renin substrate by rat liver. The present study attempts to determine if the isolated rat liver is capable of synthesizing renin substrate from 14C-labelled amino acids added in the perfusate. The renin substrate is characterized via reaction with renin, forming a substance that is subsequently identified as proangiotensin. Extensive evaluation of the reaction product is carried out by using molecular-sieve chromatography, countercurrent distribution, reactivity with converting enzyme, radioimmunological technique and bioassay. The results demonstrate that isolated rat liver perfused with artificial salt solution is capable of synthesizing a protein that reacts with renin to form a radioactive substance indistinguishable from proangiotensin."}
{"id": "PMID:230830", "title": "Phosphorylation of multiple proteins of both ribosomal subunits in rat cerebral cortex in vivo. Effect of adenosine 3':5'-cyclic monophosphate.", "content": "Investigations were carried out on the phosphorylation of ribosomal proteins in vivo in cerebral cortices of immature rats. Two-dimensional electrophoresis revealed that the cerebral 40S subunit contained at least four ribosomal proteins which were phosphorylated in animals given [32P]orthophosphate intracisternally. These proteins exhibited electrophoretic properties similar to those of the constitutive basic proteins S2, S3a, S5 and S6. The cerebral 60S subunit contained several proteins that were phosphorylated in vivo, including three basic proteins with electrophoretic mobilities similar to those of ribosomal proteins L6, L14 and L19. Four other proteins associated with the 60S subunit that were more acidic were also phosphorylated. Phosphorylated congeners of 40S and 60S ribosomal proteins could often be detected in distinct protein-stained spots on two-dimensional electrophoretograms. The cerebral S6 protein consisted of at least five distinct species in different states of phosphorylation. Administration of N6O-2' dibutyryl cyclic AMP increased the proportion of the more phosphorylated congeners of the S6 protein, but appeared to have little or no effect on phosphorylation of other cerebral ribosomal proteins. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine also stimulated S6-protein phosphorylation; N2O2'-dibutyryl cyclic GMP had no effect on this process. These observations indicate that several ribosomal proteins of both subunits are normally phosphorylated in rat cerebral cortex in situ. The results also suggest that selective and specific alterations in the phosphorylation state of the S6 ribosomal protein of the cerebral 40S subunit may accompany the production of cyclic AMP during neural activation.", "contents": "Phosphorylation of multiple proteins of both ribosomal subunits in rat cerebral cortex in vivo. Effect of adenosine 3':5'-cyclic monophosphate. Investigations were carried out on the phosphorylation of ribosomal proteins in vivo in cerebral cortices of immature rats. Two-dimensional electrophoresis revealed that the cerebral 40S subunit contained at least four ribosomal proteins which were phosphorylated in animals given [32P]orthophosphate intracisternally. These proteins exhibited electrophoretic properties similar to those of the constitutive basic proteins S2, S3a, S5 and S6. The cerebral 60S subunit contained several proteins that were phosphorylated in vivo, including three basic proteins with electrophoretic mobilities similar to those of ribosomal proteins L6, L14 and L19. Four other proteins associated with the 60S subunit that were more acidic were also phosphorylated. Phosphorylated congeners of 40S and 60S ribosomal proteins could often be detected in distinct protein-stained spots on two-dimensional electrophoretograms. The cerebral S6 protein consisted of at least five distinct species in different states of phosphorylation. Administration of N6O-2' dibutyryl cyclic AMP increased the proportion of the more phosphorylated congeners of the S6 protein, but appeared to have little or no effect on phosphorylation of other cerebral ribosomal proteins. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine also stimulated S6-protein phosphorylation; N2O2'-dibutyryl cyclic GMP had no effect on this process. These observations indicate that several ribosomal proteins of both subunits are normally phosphorylated in rat cerebral cortex in situ. The results also suggest that selective and specific alterations in the phosphorylation state of the S6 ribosomal protein of the cerebral 40S subunit may accompany the production of cyclic AMP during neural activation."}
{"id": "PMID:230831", "title": "Transient complexes. A new structural model for the activation of adenylate cyclase by hormone receptors (guanine nucleotides/irradiation inactivation).", "content": "1. The irradiation-inactivation procedure was used to study changes in the state of association of the protein components of adenylate cyclase in intact rat liver plasma membranes by measurement of alterations in the target size determined from the catalytic activity of the enzyme. 2. A decrease in target size at 30 degrees C in response to p[NH]ppG (guanosine 5'-[betagamma-imido]triphosphate) or GTP was demonstrated, which we take to reflect the dissociation of a regulatory subunit. The effect of GTP is potentiated by glucagon. This effect is not observed at 0 degrees C. 3. An increase in target size was observed in response to glucagon in the absence of guanine nucleotides, which we take to reflect the association of glucagon receptor with adenylate cyclase. 4. We propose a model for the activation of adenylate cyclase by glucagon in which the binding of the hormone to its receptor causes an initial association of the receptor with the catalytic unit of the enzyme and a regulatory subunit to form a ternary complex. The subsequent activation of the adenylate cyclase results from the dissociation of the ternary complex to leave a free catalytic unit in the activated state. This dissociation requires the binding of a guanine nucleotide to the regulatory subunit. 5. The effects of variation of temperature on the activation of adenylate cyclase by glucagon and guanine nucleotides were examined and are discussed in relation to the irradiation-activation data. 6. The effectiveness of hormones, guanine nucleotides and combinations of hormone and guanine nucleotides as activators of adenylate cyclase in both rat liver and rat fat-cell plasma membranes was studied and the results are discussed in relation to the model proposed, which is also considered in relation to the observations published by other workers.", "contents": "Transient complexes. A new structural model for the activation of adenylate cyclase by hormone receptors (guanine nucleotides/irradiation inactivation). 1. The irradiation-inactivation procedure was used to study changes in the state of association of the protein components of adenylate cyclase in intact rat liver plasma membranes by measurement of alterations in the target size determined from the catalytic activity of the enzyme. 2. A decrease in target size at 30 degrees C in response to p[NH]ppG (guanosine 5'-[betagamma-imido]triphosphate) or GTP was demonstrated, which we take to reflect the dissociation of a regulatory subunit. The effect of GTP is potentiated by glucagon. This effect is not observed at 0 degrees C. 3. An increase in target size was observed in response to glucagon in the absence of guanine nucleotides, which we take to reflect the association of glucagon receptor with adenylate cyclase. 4. We propose a model for the activation of adenylate cyclase by glucagon in which the binding of the hormone to its receptor causes an initial association of the receptor with the catalytic unit of the enzyme and a regulatory subunit to form a ternary complex. The subsequent activation of the adenylate cyclase results from the dissociation of the ternary complex to leave a free catalytic unit in the activated state. This dissociation requires the binding of a guanine nucleotide to the regulatory subunit. 5. The effects of variation of temperature on the activation of adenylate cyclase by glucagon and guanine nucleotides were examined and are discussed in relation to the irradiation-activation data. 6. The effectiveness of hormones, guanine nucleotides and combinations of hormone and guanine nucleotides as activators of adenylate cyclase in both rat liver and rat fat-cell plasma membranes was studied and the results are discussed in relation to the model proposed, which is also considered in relation to the observations published by other workers."}
{"id": "PMID:230832", "title": "Salmon calcitonin-induced stimulation of 1 alpha,25-dihydroxycholecalciferol synthesis in rats involving a mechanism independent of adenosine 3':5'-cyclic monophosphate.", "content": "The effect of natural salmon calcitonin on accumulation in plasma of 1 alpha,25-dihydroxy-[3H]cholecalciferol from 25-hydroxy[3H]cholecalciferol in vivo was investigated in vitamin D-deficient thyroparathyroidectomized rats into which graded doses of the hormone were continuously infused by use of a balance study system. A dose-dependent increase in plasma concentrations of 1 alpha,25-dihydroxy[3H]cholecalciferol was observed with calcitonin infusion for 6--30h at a rate greater than 20 M.R.C. m-units/h. Infusion of parathyrin or cyclic AMP produced a similar stimulation [Horiuchi, Suda, Takahashi, Shimazawa & Ogata (1977) Endocrinoly 101, 969--974], but the maximal effect of calcitonin was additive to that of either parathyrin or cyclic AMP. Furthermore concurrent infusion of theophylline (0.5 mumol/h) did not potentiate the effect of submaximal doses (3 and 20 M.R.C. m-units/h) of calcitonin. Plasma concentrations of calcium showed a decrease with calcitonin infusion for 30h, but those of Pi remained unchanged. These results strongly suggest that the rat kidney is endowed with a calcitonin-sensitive 1 alpha-hydroxylase system that is separate from the parathyrin/cyclic AMP system and is independent of changes in plasma Pi.", "contents": "Salmon calcitonin-induced stimulation of 1 alpha,25-dihydroxycholecalciferol synthesis in rats involving a mechanism independent of adenosine 3':5'-cyclic monophosphate. The effect of natural salmon calcitonin on accumulation in plasma of 1 alpha,25-dihydroxy-[3H]cholecalciferol from 25-hydroxy[3H]cholecalciferol in vivo was investigated in vitamin D-deficient thyroparathyroidectomized rats into which graded doses of the hormone were continuously infused by use of a balance study system. A dose-dependent increase in plasma concentrations of 1 alpha,25-dihydroxy[3H]cholecalciferol was observed with calcitonin infusion for 6--30h at a rate greater than 20 M.R.C. m-units/h. Infusion of parathyrin or cyclic AMP produced a similar stimulation [Horiuchi, Suda, Takahashi, Shimazawa & Ogata (1977) Endocrinoly 101, 969--974], but the maximal effect of calcitonin was additive to that of either parathyrin or cyclic AMP. Furthermore concurrent infusion of theophylline (0.5 mumol/h) did not potentiate the effect of submaximal doses (3 and 20 M.R.C. m-units/h) of calcitonin. Plasma concentrations of calcium showed a decrease with calcitonin infusion for 30h, but those of Pi remained unchanged. These results strongly suggest that the rat kidney is endowed with a calcitonin-sensitive 1 alpha-hydroxylase system that is separate from the parathyrin/cyclic AMP system and is independent of changes in plasma Pi."}
{"id": "PMID:230833", "title": "Inhibition of the iron-catalysed formation of hydroxyl radicals from superoxide and of lipid peroxidation by desferrioxamine.", "content": "The peroxidation of membrane phospholipids induced in vitro by ascorbic acid or by dialuric acid (hydroxybarbituric acid) does not occur in the absence of traces of metal ions. Peroxidation induced by adding iron salts to phospholipids can either be promoted or inhibited by the chelators EDTA, diethylenetriaminepenta-acetic acid and bathophenanthrolinesulphonate, depending on the ratio [chelator]/[iron salt]. The iron chelator desferrioxamine inhibits peroxidation at all concentrations tested, and it also inhibits the iron-catalysed formation of hydroxyl radicals (OH.) from superoxide (O2-.). Since desferrioxamine is approved for clinical use, it might prove a valuable tool in the treatment of inflammation, poisoning by autoxidizable molecules and radiation damage.", "contents": "Inhibition of the iron-catalysed formation of hydroxyl radicals from superoxide and of lipid peroxidation by desferrioxamine. The peroxidation of membrane phospholipids induced in vitro by ascorbic acid or by dialuric acid (hydroxybarbituric acid) does not occur in the absence of traces of metal ions. Peroxidation induced by adding iron salts to phospholipids can either be promoted or inhibited by the chelators EDTA, diethylenetriaminepenta-acetic acid and bathophenanthrolinesulphonate, depending on the ratio [chelator]/[iron salt]. The iron chelator desferrioxamine inhibits peroxidation at all concentrations tested, and it also inhibits the iron-catalysed formation of hydroxyl radicals (OH.) from superoxide (O2-.). Since desferrioxamine is approved for clinical use, it might prove a valuable tool in the treatment of inflammation, poisoning by autoxidizable molecules and radiation damage."}
{"id": "PMID:230851", "title": "[Cholera toxin induced epileptogenic focus--special reference to cyclic AMP metabolism and epileptogenic focus (author's transl)].", "content": "Epilepsy-like convulsive seizures have been induced by cholera toxin administration into the rat amygdaloid complex. Between the 8th and 48th hr after the administration, rhythmic spike discharges (1--3 spikes/sec) were electroencephalographically observed bilaterally in the amygdaloid complexes, and rats exhibited abnormal behaviors such as running, jumping, tail lifting, rearing, vocalization aggressive behavior, facial twitching and increased salivation. During these stages, high voltage spikes were intermittently observed with generalized convulsive seizures. Duration of the seizure was 1--2 min and the incidence was 0--6 times/hr. At 48 hrs after the administration or thereafter, convulsive seizures disappeared and electroencephalographic abnormalities were gradually normalized. Occasional rhythmic spike discharges, however, were observed more than 168 hrs after the administration. Since autoradiographic observations with 125I-labeled cholera toxin revealed that the injected toxin does not spread out at all from the injected site, the use of this toxin seems to be an ideal procedure to produce micro-epileptogenic foci. Cyclic AMP content as well as adenylate cyclase activity in the ipsilateral amygdaloid complex was significantly increased during preconvulsive and convulsive states. The administration of 5 x 10(-8) moles of dibutyryl cyclic AMP through the cannula implanted into the amygdaloid complex also induced behavioral and electroencephalographic abnormalities similar to those found in the cholera toxin-treated animals. These results suggest that cyclic AMP and/or cyclic AMP dependent neuronal mechanisms may play a significant role in the establishment of epileptogenic focus. Possible use of this animal model for the study of anti-epileptic drugs are also suggested.", "contents": "[Cholera toxin induced epileptogenic focus--special reference to cyclic AMP metabolism and epileptogenic focus (author's transl)]. Epilepsy-like convulsive seizures have been induced by cholera toxin administration into the rat amygdaloid complex. Between the 8th and 48th hr after the administration, rhythmic spike discharges (1--3 spikes/sec) were electroencephalographically observed bilaterally in the amygdaloid complexes, and rats exhibited abnormal behaviors such as running, jumping, tail lifting, rearing, vocalization aggressive behavior, facial twitching and increased salivation. During these stages, high voltage spikes were intermittently observed with generalized convulsive seizures. Duration of the seizure was 1--2 min and the incidence was 0--6 times/hr. At 48 hrs after the administration or thereafter, convulsive seizures disappeared and electroencephalographic abnormalities were gradually normalized. Occasional rhythmic spike discharges, however, were observed more than 168 hrs after the administration. Since autoradiographic observations with 125I-labeled cholera toxin revealed that the injected toxin does not spread out at all from the injected site, the use of this toxin seems to be an ideal procedure to produce micro-epileptogenic foci. Cyclic AMP content as well as adenylate cyclase activity in the ipsilateral amygdaloid complex was significantly increased during preconvulsive and convulsive states. The administration of 5 x 10(-8) moles of dibutyryl cyclic AMP through the cannula implanted into the amygdaloid complex also induced behavioral and electroencephalographic abnormalities similar to those found in the cholera toxin-treated animals. These results suggest that cyclic AMP and/or cyclic AMP dependent neuronal mechanisms may play a significant role in the establishment of epileptogenic focus. Possible use of this animal model for the study of anti-epileptic drugs are also suggested."}
{"id": "PMID:230853", "title": "Triple hormone-receptor assay: a more accurate predictive tool for the treatment of advanced breast cancer?", "content": "In a group of 74 patients with advanced metastatic breast cancer, 57% of those with cytoplasmic oestrogen receptor activity in their tumours (REC+) showed a clinical response to endocrine therapy. Of 51 patients whose tumour was assayed for both REC and cytoplasmic progesterone (RPC) activity, 9/12 patients with REC+ RPC+ tumours responded to hormone treatment, whereas only 3/30 patients with REC-RPC-tumours had a clinical response. In a group of 19 patients in whom nuclear oestrogen receptor (REN) was also estimated in the pellets from tumour-tissue homogenates, 5/6 with tumours positive for all 3 receptors showed a clinical response. None of the 9 patients with triply negative tumours responded. Addition of the REN assay appears to reinforce the greater precision of prediction when RPC as well as REC are estimated in breast tumours.", "contents": "Triple hormone-receptor assay: a more accurate predictive tool for the treatment of advanced breast cancer? In a group of 74 patients with advanced metastatic breast cancer, 57% of those with cytoplasmic oestrogen receptor activity in their tumours (REC+) showed a clinical response to endocrine therapy. Of 51 patients whose tumour was assayed for both REC and cytoplasmic progesterone (RPC) activity, 9/12 patients with REC+ RPC+ tumours responded to hormone treatment, whereas only 3/30 patients with REC-RPC-tumours had a clinical response. In a group of 19 patients in whom nuclear oestrogen receptor (REN) was also estimated in the pellets from tumour-tissue homogenates, 5/6 with tumours positive for all 3 receptors showed a clinical response. None of the 9 patients with triply negative tumours responded. Addition of the REN assay appears to reinforce the greater precision of prediction when RPC as well as REC are estimated in breast tumours."}
{"id": "PMID:230854", "title": "Growth pattern of tumours in mice induced by murine Moloney sarcoma-virus and sarcoma-virus-transformed cells.", "content": "Transplantation of a Moloney sarcoma-virus (MSV-M)-transformed producer cell line (Sac(+)) induced progressively or regressively growing tumours in mice. Progressive growth always occurred after transplantation of an MSV-M non-producer transformant (Sac(-)), whereas the MSV-M released from the producer cells (Sac virus) always induced tumours which regressed. In contrast to the non-producer, the producer transformant Sac(+) as well as Sac virus induced a strong immune response, detected in vitro by cell- and antibody-mediated cytotoxicity assays, and in vivo by transplantation immunity. Implantation of Sac(-) cells led to solid, under-vascularized tumours, consisting histologically of uniform densely packed tumour cells. Sac-virus-induced tumours, however, were very well vascularized and arose by proliferation of different connective-tissue cells. After transplantation of Sac(+) cells, tumours were found to consist of typical tumour cells morphologically similar to Sac(-) cells intermingled with proliferated connective-tissue cells. Cultivation of tumour fragments from Sac(+) and Sac(-) tumours was followed by outgrowth of transformed tumour cells with the properties of the originally implanted cells. Tumour explant cultures from Sac-virus-induced tumours did not lead to growth of stably transformed cells. Co-culture of mouse embryo fibroblasts (MEF) with Sac(+) cells resulted in overgrowth of the transformed cells. Infection of MEF with Sac virus led to transiently transformed cells. It is concluded that Sac(+) cell tumours will resist the strong immune defence mechanisms they induce and grow progressively, if the inoculated cells are able to build up a solid, poorly vascularized nodule in the tissue. This always happens after implantation of 10(6) cells, but only occasionally when fewer cells are inoculated. Sac-virus-induced tumours will always regress owing to the strong immune response. The regression is furthered by the fact that MSV-M infection rarely if ever leads to a stable transformation.", "contents": "Growth pattern of tumours in mice induced by murine Moloney sarcoma-virus and sarcoma-virus-transformed cells. Transplantation of a Moloney sarcoma-virus (MSV-M)-transformed producer cell line (Sac(+)) induced progressively or regressively growing tumours in mice. Progressive growth always occurred after transplantation of an MSV-M non-producer transformant (Sac(-)), whereas the MSV-M released from the producer cells (Sac virus) always induced tumours which regressed. In contrast to the non-producer, the producer transformant Sac(+) as well as Sac virus induced a strong immune response, detected in vitro by cell- and antibody-mediated cytotoxicity assays, and in vivo by transplantation immunity. Implantation of Sac(-) cells led to solid, under-vascularized tumours, consisting histologically of uniform densely packed tumour cells. Sac-virus-induced tumours, however, were very well vascularized and arose by proliferation of different connective-tissue cells. After transplantation of Sac(+) cells, tumours were found to consist of typical tumour cells morphologically similar to Sac(-) cells intermingled with proliferated connective-tissue cells. Cultivation of tumour fragments from Sac(+) and Sac(-) tumours was followed by outgrowth of transformed tumour cells with the properties of the originally implanted cells. Tumour explant cultures from Sac-virus-induced tumours did not lead to growth of stably transformed cells. Co-culture of mouse embryo fibroblasts (MEF) with Sac(+) cells resulted in overgrowth of the transformed cells. Infection of MEF with Sac virus led to transiently transformed cells. It is concluded that Sac(+) cell tumours will resist the strong immune defence mechanisms they induce and grow progressively, if the inoculated cells are able to build up a solid, poorly vascularized nodule in the tissue. This always happens after implantation of 10(6) cells, but only occasionally when fewer cells are inoculated. Sac-virus-induced tumours will always regress owing to the strong immune response. The regression is furthered by the fact that MSV-M infection rarely if ever leads to a stable transformation."}
{"id": "PMID:230855", "title": "SV40 T-antigen expression in acute non-lymphocytic leukaemia.", "content": "Susceptibility to SV40 virus infection has been suggested as an in vitro marker of predisposition to leukaemia and possibly other cancers in man. To evaluate this relationship, sporadic as well as familial cases of acute non-lymphocytic leukaemia were tested. Among skin fibroblast lines from 22 patients without family history of leukaemia, eight had values above the 95% confidence limit for the normal control population. In four leukaemia-prone families, elevated T-antigen expression was found in all four patients tested and in three-quarters of 36 blood relatives. In addition, elevated values were found in two of three cases of acute myelogenous leukaemia associated with constitutional cytogenetic anomalies, and in all three cases with preleukaemic haematologic disorders. Since SV40 T-antigen expression was elevated in most persons prone to acute non-lymphocytic leukaemia, as well as over one-third of sporadic cases, heritable risk factors may be involved in both groups.", "contents": "SV40 T-antigen expression in acute non-lymphocytic leukaemia. Susceptibility to SV40 virus infection has been suggested as an in vitro marker of predisposition to leukaemia and possibly other cancers in man. To evaluate this relationship, sporadic as well as familial cases of acute non-lymphocytic leukaemia were tested. Among skin fibroblast lines from 22 patients without family history of leukaemia, eight had values above the 95% confidence limit for the normal control population. In four leukaemia-prone families, elevated T-antigen expression was found in all four patients tested and in three-quarters of 36 blood relatives. In addition, elevated values were found in two of three cases of acute myelogenous leukaemia associated with constitutional cytogenetic anomalies, and in all three cases with preleukaemic haematologic disorders. Since SV40 T-antigen expression was elevated in most persons prone to acute non-lymphocytic leukaemia, as well as over one-third of sporadic cases, heritable risk factors may be involved in both groups."}
{"id": "PMID:230857", "title": "Characterization of simian virus 40 transcriptional intermediates in infected CV1 cell nuclei.", "content": "Simian Virus (SV40) transcriptional intermediates (T.I.) were isolated from infected cell nuclei incubated in vitro in the presence of the four ribonucleoside triphosphates. The nascent mRNA strands in the viral DNA-RNA hybrid molecules were hydrogen bonded to their template by 200-250 nucleotides on the average, as judged from the extent of their RNase resistance and the aspect of T.I. under electron microscope after treatment with 50 per cent formamide. The RNA polymerase involved (RNA polymerase II) synthesized up to full length transcripts at a rate of approximately 150 nucleotides/min. at 25 degrees C. Each SV40 infected cell was found to contain about 200 active T.I. molecules at the peak of late transcription. The DNA in the T.I. molecules was exclusively form I DNA only in cell infected with the tsA30 mutant of SV40 that had been transferred to non-permissive temperature in order to arrest DNA replication, but both form I DNA and molecules behaving as replicative intermediates (R.I.) in wild type infected cells.", "contents": "Characterization of simian virus 40 transcriptional intermediates in infected CV1 cell nuclei. Simian Virus (SV40) transcriptional intermediates (T.I.) were isolated from infected cell nuclei incubated in vitro in the presence of the four ribonucleoside triphosphates. The nascent mRNA strands in the viral DNA-RNA hybrid molecules were hydrogen bonded to their template by 200-250 nucleotides on the average, as judged from the extent of their RNase resistance and the aspect of T.I. under electron microscope after treatment with 50 per cent formamide. The RNA polymerase involved (RNA polymerase II) synthesized up to full length transcripts at a rate of approximately 150 nucleotides/min. at 25 degrees C. Each SV40 infected cell was found to contain about 200 active T.I. molecules at the peak of late transcription. The DNA in the T.I. molecules was exclusively form I DNA only in cell infected with the tsA30 mutant of SV40 that had been transferred to non-permissive temperature in order to arrest DNA replication, but both form I DNA and molecules behaving as replicative intermediates (R.I.) in wild type infected cells."}
{"id": "PMID:230860", "title": "Effects of cyanogenic agents on reproduction and neonatal development in rats.", "content": "A diet consisting of 50% gari (a form of cassava meal) was found to cause no significant biochemical and haematological changes in adult female rats. Although this diet caused a significant increase in their serum thiocyanate levels, there was no corresponding significant increase in the weight of their thyroid glands. The offspring of these rats had significantly lower birth weights and brain weights and never attained the same adult weights as those of the controls. Adult female rats fed a diet consisting entirely of raw cassava had significantly reduced haematological and biochemical indices. This diet also caused an increased incidence of cannibalism and a significant reduction in the frequency of pregnancy, the average number of the litter and the birth weights among these rats. In addition there was an increased incidence of neonatal deaths among the offspring which also had poor development, reduced brain weights and an increased tendency towards biting their litter-mates. Adult female rats fed diets containing 5 and 10 g cyanide/100 g laboratory diet survived for more than 3 months but never became pregnant. They developed enlarged thyroid glands and tumours of the large intestine. The relevance of these findings to the areas of the world where cyanogenic glycosides form the staple diet is discussed.", "contents": "Effects of cyanogenic agents on reproduction and neonatal development in rats. A diet consisting of 50% gari (a form of cassava meal) was found to cause no significant biochemical and haematological changes in adult female rats. Although this diet caused a significant increase in their serum thiocyanate levels, there was no corresponding significant increase in the weight of their thyroid glands. The offspring of these rats had significantly lower birth weights and brain weights and never attained the same adult weights as those of the controls. Adult female rats fed a diet consisting entirely of raw cassava had significantly reduced haematological and biochemical indices. This diet also caused an increased incidence of cannibalism and a significant reduction in the frequency of pregnancy, the average number of the litter and the birth weights among these rats. In addition there was an increased incidence of neonatal deaths among the offspring which also had poor development, reduced brain weights and an increased tendency towards biting their litter-mates. Adult female rats fed diets containing 5 and 10 g cyanide/100 g laboratory diet survived for more than 3 months but never became pregnant. They developed enlarged thyroid glands and tumours of the large intestine. The relevance of these findings to the areas of the world where cyanogenic glycosides form the staple diet is discussed."}
{"id": "PMID:230861", "title": "Development of phosphoenolpyruvate carboxykinase ferroactivator in fetal and young rats and guinea pigs.", "content": "The development of ferroactivator, a protein that permits Fe2+ to activate the gluconeogenic enzyme phosphoenolpyruvate carboxykinase, was compared to that of the carboxykinase in rat and guinea pig fetuses and neonates. Significant ferroactivator was present in the liver of the fetal rat and in the liver and kidney of the fetal guinea pig in the last half of gestation. The development of ferroactivator does not parallel that of the carboxykinase which does not attain maximal levels until after birth. Thus, the ferroactivator cannot be rate limiting for neonatal gluconeogenesis. It was found, unexpectedly, that the carboxykinase was increased during suckling in the guinea pig.", "contents": "Development of phosphoenolpyruvate carboxykinase ferroactivator in fetal and young rats and guinea pigs. The development of ferroactivator, a protein that permits Fe2+ to activate the gluconeogenic enzyme phosphoenolpyruvate carboxykinase, was compared to that of the carboxykinase in rat and guinea pig fetuses and neonates. Significant ferroactivator was present in the liver of the fetal rat and in the liver and kidney of the fetal guinea pig in the last half of gestation. The development of ferroactivator does not parallel that of the carboxykinase which does not attain maximal levels until after birth. Thus, the ferroactivator cannot be rate limiting for neonatal gluconeogenesis. It was found, unexpectedly, that the carboxykinase was increased during suckling in the guinea pig."}
{"id": "PMID:230864", "title": "Increase of neutrophil alkaline phosphatase in the mothers of leukemic children.", "content": "A comparative study of the polymorphonuclear neutrophiles of 62 parents of children suffering from acute leukemia and of 110 couples with normal children revealed a marked increased of Neutrophil Alkaline Phosphatase (p less than 0.05) in the mothers of the leukemic children. The other parameters (periodic acid Schiff and myeloperoxidase) were unchanged.", "contents": "Increase of neutrophil alkaline phosphatase in the mothers of leukemic children. A comparative study of the polymorphonuclear neutrophiles of 62 parents of children suffering from acute leukemia and of 110 couples with normal children revealed a marked increased of Neutrophil Alkaline Phosphatase (p less than 0.05) in the mothers of the leukemic children. The other parameters (periodic acid Schiff and myeloperoxidase) were unchanged."}
{"id": "PMID:230865", "title": "Collagen metabolism in the liver of normal and carbon tetrachloride treated rats.", "content": "A significant increase in the activity of prolyl hydroxylase, in the relative collagen synthesis and in the hydroxyproline content was observed in the liver of rats treated for five weeks with CCl4 when compared to control liver. Five weeks after the suspension of the treatment, the activity of prolyl hydroxylase and the relative collagen synthesis returned to normal, but the hydroxyproline content of the liver of the CCl4-treated animals remained significantly higher than that of the controls. These findings suggest that an impairment in the mechanisms responsible for the resorption of the scar tissue could account for the accumulation of collagen within the parenchyma in liver fibrosis.", "contents": "Collagen metabolism in the liver of normal and carbon tetrachloride treated rats. A significant increase in the activity of prolyl hydroxylase, in the relative collagen synthesis and in the hydroxyproline content was observed in the liver of rats treated for five weeks with CCl4 when compared to control liver. Five weeks after the suspension of the treatment, the activity of prolyl hydroxylase and the relative collagen synthesis returned to normal, but the hydroxyproline content of the liver of the CCl4-treated animals remained significantly higher than that of the controls. These findings suggest that an impairment in the mechanisms responsible for the resorption of the scar tissue could account for the accumulation of collagen within the parenchyma in liver fibrosis."}
{"id": "PMID:230867", "title": "Recent developments in the estimation of trace toxic substances in food.", "content": "A survey has been made of about 120 papers appearing in the food literature in which mass spectrometry has been employed to measure toxic contaminant levels. The areas covered are, mycotoxins, nitrosamines, polyhalogenated hydrocarbons and other industrial contaminants. All the essential analytical details have been collected and the limitations of the present day methods are discussed. The reader may conclude that sometimes there is a lack of essential information and that a more standard reporting procedure for quantitative assays is needed.", "contents": "Recent developments in the estimation of trace toxic substances in food. A survey has been made of about 120 papers appearing in the food literature in which mass spectrometry has been employed to measure toxic contaminant levels. The areas covered are, mycotoxins, nitrosamines, polyhalogenated hydrocarbons and other industrial contaminants. All the essential analytical details have been collected and the limitations of the present day methods are discussed. The reader may conclude that sometimes there is a lack of essential information and that a more standard reporting procedure for quantitative assays is needed."}
{"id": "PMID:230868", "title": "Studies on the control of respiration and behaviour during development in ewe-reared lambs.", "content": "Radiotelemetric recordings have been made in a series of newborn lambs with implanted electrodes and transducers and an external back-pack transmitter. Cardiac, respiratory and behavioural data have been gathered. These data have been analysed firstly with respect to age. The cardiac and respiratory data have then been related to both sleep state and age. An unexpected rise in both heart and respiratory rates was found after birth and marked differences were obvious in respiratory control in REM and non-REM sleep states.", "contents": "Studies on the control of respiration and behaviour during development in ewe-reared lambs. Radiotelemetric recordings have been made in a series of newborn lambs with implanted electrodes and transducers and an external back-pack transmitter. Cardiac, respiratory and behavioural data have been gathered. These data have been analysed firstly with respect to age. The cardiac and respiratory data have then been related to both sleep state and age. An unexpected rise in both heart and respiratory rates was found after birth and marked differences were obvious in respiratory control in REM and non-REM sleep states."}
{"id": "PMID:230870", "title": "Excitability and NADH fluorescence of spontaneously active portal veins in relation to glucose withdrawal.", "content": "The effect of glucose withdrawal upon mechanical activity and the redox level of pyridine nucleotides and flavoproteins was investigated in isolated rat portal veins under aerobic conditions. A decrease of extracellular glucose concentration correlated with contractile activity. During acetylcholine-induced tetanic contractions. NADH and flavoproteins were oxydized only in vessels supplied with glucose. The myogenic activity was restituted when glucose was added after withdrawal parallel with a reduction of NAD and flavoproteins. The results suggest that glucose, besides its effect on the energy metabolism, has an influence on the excitability of smooth muscle cells of rat portal veins.", "contents": "Excitability and NADH fluorescence of spontaneously active portal veins in relation to glucose withdrawal. The effect of glucose withdrawal upon mechanical activity and the redox level of pyridine nucleotides and flavoproteins was investigated in isolated rat portal veins under aerobic conditions. A decrease of extracellular glucose concentration correlated with contractile activity. During acetylcholine-induced tetanic contractions. NADH and flavoproteins were oxydized only in vessels supplied with glucose. The myogenic activity was restituted when glucose was added after withdrawal parallel with a reduction of NAD and flavoproteins. The results suggest that glucose, besides its effect on the energy metabolism, has an influence on the excitability of smooth muscle cells of rat portal veins."}
{"id": "PMID:230871", "title": "Effect of adenosine on adrenergic neurotransmission in the superfused rat portal vein.", "content": "This study examined the effect of exogenously applied adenosine on the release of 3H-norepinephrine from the field-stimulated, superfused rat portal vein. Adenosine was found to inhibit the field-stimulated release of 3H-norepinephrine in a dose-dependent manner in 50- to 1,000-microM concentrations. The effect was reversed when adenosine was washed out. The inhibitory effects of adenosine were antagonized by theophylline (10-4 M) which by itself showed a slight enhancement of stimulated 3H-norepinephrine release. ATP was found to inhibit 3H-norepinephrine release at the same concentration as adenosine while inosine was inactive. When adenosine was tested in the presence of the muscarinic and alpha-adrenergic blocking agents atropine and phenoxybenzamine along with indomethacin, a prostaglandin synthesis inhibitor, its inhibotory effect on the stimulated release of 3H-norepinephrine persisted. It is concluded that adenosine and/or ATP can modulate the nerve-stimulated induced release of norepinephrine presumably by an action on the adrenergic nerve terminals.", "contents": "Effect of adenosine on adrenergic neurotransmission in the superfused rat portal vein. This study examined the effect of exogenously applied adenosine on the release of 3H-norepinephrine from the field-stimulated, superfused rat portal vein. Adenosine was found to inhibit the field-stimulated release of 3H-norepinephrine in a dose-dependent manner in 50- to 1,000-microM concentrations. The effect was reversed when adenosine was washed out. The inhibitory effects of adenosine were antagonized by theophylline (10-4 M) which by itself showed a slight enhancement of stimulated 3H-norepinephrine release. ATP was found to inhibit 3H-norepinephrine release at the same concentration as adenosine while inosine was inactive. When adenosine was tested in the presence of the muscarinic and alpha-adrenergic blocking agents atropine and phenoxybenzamine along with indomethacin, a prostaglandin synthesis inhibitor, its inhibotory effect on the stimulated release of 3H-norepinephrine persisted. It is concluded that adenosine and/or ATP can modulate the nerve-stimulated induced release of norepinephrine presumably by an action on the adrenergic nerve terminals."}
{"id": "PMID:230872", "title": "[The activity of cytochrome oxidase in the normal cerebral cortex and after destructive and irritating lesions. Histochemical research].", "content": "Production of an epileptogenic focus by cobalt-gelatin implantation in the cerebral cortex of the rat determines a local increase of cytochrome oxidase activity in neurones and probably a decrease of its activity in neuroglia. This variation of oxidative metabolism is not characteristic of the \"epileptic neuron\" since it takes also place after non irritative lesions, though remaining less conspicuous and less extensive.", "contents": "[The activity of cytochrome oxidase in the normal cerebral cortex and after destructive and irritating lesions. Histochemical research]. Production of an epileptogenic focus by cobalt-gelatin implantation in the cerebral cortex of the rat determines a local increase of cytochrome oxidase activity in neurones and probably a decrease of its activity in neuroglia. This variation of oxidative metabolism is not characteristic of the \"epileptic neuron\" since it takes also place after non irritative lesions, though remaining less conspicuous and less extensive."}
{"id": "PMID:230873", "title": "[Comparative study of anti EBV antibodies in non-Hodgkin's lymphomams and angio-immunoblastic lymphadenopathies (author's transl)].", "content": "Antibody titers to Epstein-Barr virus (EBV)--related antigens (viral capsid antigen : VCA; early antigen : EA; and EBV associated nuclear antigen : EBNA) were determined in the sera of 86 patients and 150 matched control subjects. The patients belonged to four histological groups : diffuse and nodular non-hodgkin's lymphomas angio-immunoblastic lymphadenopathies and apparented syndroms. The incidence of antibodies to other herpes-viruses (cytom\u00e9galovirus, herpes simplex virus, and varicella zoster virus) was compared. There was a significantly higher incidence of anti VCA and anti EA titers in some patients, not associated with an increase in titres of antibodies to other herpes viruses.", "contents": "[Comparative study of anti EBV antibodies in non-Hodgkin's lymphomams and angio-immunoblastic lymphadenopathies (author's transl)]. Antibody titers to Epstein-Barr virus (EBV)--related antigens (viral capsid antigen : VCA; early antigen : EA; and EBV associated nuclear antigen : EBNA) were determined in the sera of 86 patients and 150 matched control subjects. The patients belonged to four histological groups : diffuse and nodular non-hodgkin's lymphomas angio-immunoblastic lymphadenopathies and apparented syndroms. The incidence of antibodies to other herpes-viruses (cytom\u00e9galovirus, herpes simplex virus, and varicella zoster virus) was compared. There was a significantly higher incidence of anti VCA and anti EA titers in some patients, not associated with an increase in titres of antibodies to other herpes viruses."}
{"id": "PMID:230875", "title": "[Epidemiology of carcinoma of the cervix (author's transl)].", "content": "In order to explain why modes of sexual life influence the incidence of cervical carcinoma, several factors have been claimed to be involved. There is no solid basis for the hypothesis that sperm may be mutagenic. By contrast, epidemiological studies showed that partners whose life is not sedentary bring back home to their wives an increased risk of cervical carcinoma. The infectious factor does not seem to be associated with syphilis but may well be represented by herpes genitalis virus (Herpes Simplex type 2 virus). Women with cervical carcinoma show a variety of immunes reactions to this virus, and these reactions are statistically less frequent in control groups. In the laboratory, mouse and hamster cells have been transformed into cancerous cells by means of herpes simplex virus type 2.", "contents": "[Epidemiology of carcinoma of the cervix (author's transl)]. In order to explain why modes of sexual life influence the incidence of cervical carcinoma, several factors have been claimed to be involved. There is no solid basis for the hypothesis that sperm may be mutagenic. By contrast, epidemiological studies showed that partners whose life is not sedentary bring back home to their wives an increased risk of cervical carcinoma. The infectious factor does not seem to be associated with syphilis but may well be represented by herpes genitalis virus (Herpes Simplex type 2 virus). Women with cervical carcinoma show a variety of immunes reactions to this virus, and these reactions are statistically less frequent in control groups. In the laboratory, mouse and hamster cells have been transformed into cancerous cells by means of herpes simplex virus type 2."}
{"id": "PMID:230877", "title": "Temperature and inhibitory junctional transmission in guinea-pig ileum.", "content": "The effects of temperature on the inhibitory junctional potential (i.j.p.) and the electrotonic potential, recorded in the circular smooth muscle of the guinea-pig ileum, were studied with intracellular microelectrodes. The amplitude and time course of the i.j.p. were both dependent on the ambient temperature, the i.j.p. becoming smaller and more prolonged as the temperature was lowered. In contrast, the electrotonic potential was not much affected by temperature. The atropine-resistant 'late' depolarization was also dependent on temperature. These results are consistent with the mechanism of release, of the nonadrenergic noncholinergic inhibitory transmitter, being sensitive to temperature and with the inhibitory conductance change, underlying the i.j.p., being long compared to the membrane time constant of the circular smooth muscle.", "contents": "Temperature and inhibitory junctional transmission in guinea-pig ileum. The effects of temperature on the inhibitory junctional potential (i.j.p.) and the electrotonic potential, recorded in the circular smooth muscle of the guinea-pig ileum, were studied with intracellular microelectrodes. The amplitude and time course of the i.j.p. were both dependent on the ambient temperature, the i.j.p. becoming smaller and more prolonged as the temperature was lowered. In contrast, the electrotonic potential was not much affected by temperature. The atropine-resistant 'late' depolarization was also dependent on temperature. These results are consistent with the mechanism of release, of the nonadrenergic noncholinergic inhibitory transmitter, being sensitive to temperature and with the inhibitory conductance change, underlying the i.j.p., being long compared to the membrane time constant of the circular smooth muscle."}
{"id": "PMID:230884", "title": "Prevalence of nine different micro-organisms in the female genital tract. A comparison between women from a venereal disease clinic and from a health control department.", "content": "In a study of the prevalence of nine different micro-organisms in the female genital tract in a Swedish population, significantly higher isolation rates occurred among women attending a venereal disease clinic than among those attending a gynaecological health control department. The prevalence of Candida albicans, however, was similar in different groups, individual susceptibility being the most important factor. Chlamydia trachomatis, Trichomonas vaginalis, and Mycoplasma hominis occurred concomitantly with Neisseria gonorrhoeae, indicating a similar epidemiology for all these agents. Younger patients seemed to have an increased susceptibility to C. trachomatis whereas older patients had an increased susceptibility to T. vaginalis.", "contents": "Prevalence of nine different micro-organisms in the female genital tract. A comparison between women from a venereal disease clinic and from a health control department. In a study of the prevalence of nine different micro-organisms in the female genital tract in a Swedish population, significantly higher isolation rates occurred among women attending a venereal disease clinic than among those attending a gynaecological health control department. The prevalence of Candida albicans, however, was similar in different groups, individual susceptibility being the most important factor. Chlamydia trachomatis, Trichomonas vaginalis, and Mycoplasma hominis occurred concomitantly with Neisseria gonorrhoeae, indicating a similar epidemiology for all these agents. Younger patients seemed to have an increased susceptibility to C. trachomatis whereas older patients had an increased susceptibility to T. vaginalis."}
{"id": "PMID:230887", "title": "[Immunocytologic analysis, in rat hypothalamus, of neurons producing peptides related to endorphin, ACTH, MSH and beta-LPH. Comparison with other peptidergic and monoaminergic neurons].", "content": "In rat hypothalamus intraventricularly injected with colchicine, the same neurons of the ventral region are stained with I.S. against alpha and beta-endorphin, (1-24) and (17-39) ACTH, alpha and beta-MSH, and beta-LPH. They are distinct from those producing LH-RH, somatostatin, neurophysin, and dopamine. These results suggest that the same neurons elaborate peptides identical with or immunologically related to endorphins, ACTH, alpha-MSH and beta-LPH, probably issued from a common precursor.", "contents": "[Immunocytologic analysis, in rat hypothalamus, of neurons producing peptides related to endorphin, ACTH, MSH and beta-LPH. Comparison with other peptidergic and monoaminergic neurons]. In rat hypothalamus intraventricularly injected with colchicine, the same neurons of the ventral region are stained with I.S. against alpha and beta-endorphin, (1-24) and (17-39) ACTH, alpha and beta-MSH, and beta-LPH. They are distinct from those producing LH-RH, somatostatin, neurophysin, and dopamine. These results suggest that the same neurons elaborate peptides identical with or immunologically related to endorphins, ACTH, alpha-MSH and beta-LPH, probably issued from a common precursor."}
{"id": "PMID:230888", "title": "[Evidence for the production of a fusion factor during in vitro infection of sheep choroid plexus cells by visna virus].", "content": "One of the most important early events during the infection of sheep choro\u00efd plexus cells in culture by Visna virus is the synthesis by these cells of a fusion factor distinct from the virus. The cell fusion activity of this factor does not seem transmissible. It promotes cell shape changes and a migration of the nucleus towards the cell wall.", "contents": "[Evidence for the production of a fusion factor during in vitro infection of sheep choroid plexus cells by visna virus]. One of the most important early events during the infection of sheep choro\u00efd plexus cells in culture by Visna virus is the synthesis by these cells of a fusion factor distinct from the virus. The cell fusion activity of this factor does not seem transmissible. It promotes cell shape changes and a migration of the nucleus towards the cell wall."}
{"id": "PMID:230889", "title": "[Comparative adrenergic activity in the Long Evans and Sprague Dawley rat].", "content": "Sprague Dawley rats show a more pronounced reactivity of their alpha and beta receptors than Long Evans rats after an infusion of noradrenaline.", "contents": "[Comparative adrenergic activity in the Long Evans and Sprague Dawley rat]. Sprague Dawley rats show a more pronounced reactivity of their alpha and beta receptors than Long Evans rats after an infusion of noradrenaline."}
{"id": "PMID:230885", "title": "Multiunit activity in the mesencephalic reticular formation and septal area of freely moving newborn rat.", "content": "A surgical technique to implant stereotaxically fixed probes for recording multiunit activity /MUA/ from the mesencephalic reticular formation and septal area of freely moving 6--12 hr old newborn rat is described. In both brain areas the spontaneous firing of neuron populations showed close correlation with the stages of wakefulness and sleep cycle.", "contents": "Multiunit activity in the mesencephalic reticular formation and septal area of freely moving newborn rat. A surgical technique to implant stereotaxically fixed probes for recording multiunit activity /MUA/ from the mesencephalic reticular formation and septal area of freely moving 6--12 hr old newborn rat is described. In both brain areas the spontaneous firing of neuron populations showed close correlation with the stages of wakefulness and sleep cycle."}
{"id": "PMID:230890", "title": "Virus detection in soils: a comparison of four recovery methods.", "content": "Among nine eluents tested, 0.5% (w/v) isoelectric casein at pH 9.0 and 0.5% (w/v) non-fat dry milk (pH 9.0) were the most efficient in eluting poliovirus type 1 (Sabin) from Eustis fine sand. However, no significant difference was found between the overall (elution followed by concentration) virus recoveries by non-fat dry milk, isoelectric casein, beef extract, and glycine-EDTA methods. High overall recovery (75%) of low input (200 PFU) of viruses from 100 g of soil was achieved by the isoelectric casein method. It was found that the recovery efficiency of this method was not significantly affected by the soil type, following examination of four Florida soils. The mean overall recovery for the four soils was 50%. For other enteroviruses, the overall recovery for coxsackie B3 was 88% but was significantly lower (23%) for echovirus 4. Examination of the efficiency of the casein method under field conditions showed that it was possible to recovery low poliovirus numbers from soil (0.9-1.3 PFU/g soil).", "contents": "Virus detection in soils: a comparison of four recovery methods. Among nine eluents tested, 0.5% (w/v) isoelectric casein at pH 9.0 and 0.5% (w/v) non-fat dry milk (pH 9.0) were the most efficient in eluting poliovirus type 1 (Sabin) from Eustis fine sand. However, no significant difference was found between the overall (elution followed by concentration) virus recoveries by non-fat dry milk, isoelectric casein, beef extract, and glycine-EDTA methods. High overall recovery (75%) of low input (200 PFU) of viruses from 100 g of soil was achieved by the isoelectric casein method. It was found that the recovery efficiency of this method was not significantly affected by the soil type, following examination of four Florida soils. The mean overall recovery for the four soils was 50%. For other enteroviruses, the overall recovery for coxsackie B3 was 88% but was significantly lower (23%) for echovirus 4. Examination of the efficiency of the casein method under field conditions showed that it was possible to recovery low poliovirus numbers from soil (0.9-1.3 PFU/g soil)."}
{"id": "PMID:230886", "title": "Hibernation: an opioid-dependent state?", "content": "Hibernation reduces substantially the heart rate of hamsters as well as the respiratory rate, the body temperature and the arousal level. The heart rate is reversed dramatically by the injection of low doses of Naloxone and in some cases the hamster arouses prematurely from hibernation. The effect is not due to the pain of the injection because saline injections do not produce such changes. The effect requires a pre-existing state of hibernation because Naloxone has no cardioacceleratory or arousal effect in non-hibernating hamsters that have had their heart rate and body temperature decreased substantially during hypothermia. These results suggest that endogenous opioids may contribute specifically to the state of hibernation. Moreover, a physiological role may exist for an anti-opioid system in the promotion of arousal from hibernation.", "contents": "Hibernation: an opioid-dependent state? Hibernation reduces substantially the heart rate of hamsters as well as the respiratory rate, the body temperature and the arousal level. The heart rate is reversed dramatically by the injection of low doses of Naloxone and in some cases the hamster arouses prematurely from hibernation. The effect is not due to the pain of the injection because saline injections do not produce such changes. The effect requires a pre-existing state of hibernation because Naloxone has no cardioacceleratory or arousal effect in non-hibernating hamsters that have had their heart rate and body temperature decreased substantially during hypothermia. These results suggest that endogenous opioids may contribute specifically to the state of hibernation. Moreover, a physiological role may exist for an anti-opioid system in the promotion of arousal from hibernation."}
{"id": "PMID:230891", "title": "Extramammary Paget's disease.", "content": "In a 74-year-old man extramammary Paget's disease of the scrotal and perianal areas masqueraded as tinea cruris and chronic dermatitis for 7 years before it was diagnosed. Topical therapy with 1% 5-fluorouracil cream resulted in clinical improvement but not histologic clearing.", "contents": "Extramammary Paget's disease. In a 74-year-old man extramammary Paget's disease of the scrotal and perianal areas masqueraded as tinea cruris and chronic dermatitis for 7 years before it was diagnosed. Topical therapy with 1% 5-fluorouracil cream resulted in clinical improvement but not histologic clearing."}
{"id": "PMID:230892", "title": "Serological survey for Aujeszky's disease in native sows of Canada.", "content": "A serological survey was initiated to uncover subclinical foci of infection with pseudorabies virus. A total of 2819 serum samples, collected from sows during February to November 1977, were found negative for antibodies to pseudorabies virus.", "contents": "Serological survey for Aujeszky's disease in native sows of Canada. A serological survey was initiated to uncover subclinical foci of infection with pseudorabies virus. A total of 2819 serum samples, collected from sows during February to November 1977, were found negative for antibodies to pseudorabies virus."}
{"id": "PMID:230893", "title": "Treatment of grade III and IV astrocytomas with BCNU alone and in combination with VM-26 following surgery and radiation therapy.", "content": "Twenty-one patients with grade III or IV astrocytomas were assigned randomly to receive either BCNU alone or BCNU and VM-26 after surgery and radiation therapy. Patients surviving radiation therapy and receiving single-agent chemotherapy had a median survival of 14 months while those receiving combination chemotherapy had a median survival of 22 months (P greater than 0.05). None of the patients who failed BCNU-only therapy responded to VM-26. Performance status was not affected by either regimen. Computerized tomographic scanning of the brain was useful only in confirming tumor progression. Two patients died from BCNU-related interstitial pulmonary fibrosis.", "contents": "Treatment of grade III and IV astrocytomas with BCNU alone and in combination with VM-26 following surgery and radiation therapy. Twenty-one patients with grade III or IV astrocytomas were assigned randomly to receive either BCNU alone or BCNU and VM-26 after surgery and radiation therapy. Patients surviving radiation therapy and receiving single-agent chemotherapy had a median survival of 14 months while those receiving combination chemotherapy had a median survival of 22 months (P greater than 0.05). None of the patients who failed BCNU-only therapy responded to VM-26. Performance status was not affected by either regimen. Computerized tomographic scanning of the brain was useful only in confirming tumor progression. Two patients died from BCNU-related interstitial pulmonary fibrosis."}
{"id": "PMID:230894", "title": "Tamoxifen-induced tumor stimulation and withdrawal response.", "content": "A postmenopausal breast cancer patient with a measurable lung metastasis was treated with tamoxifen. The tumor doubling time of the pulmonary lesion was 140 days during spontaneous growth and 52 days during tamoxifen therapy, an almost threefold increase in tumor growth rate. This stimulation persisted fro 1 month after discontinuation of tamoxifen and was followed thereafter by a withdrawal regression lasting greater than 6 months. Awareness of the possible tumor growth enhancement with tamoxifen is of importance especially in view of its prolonged activity. Hormone withdrawal regression may occur following tamoxifen therapy, and a sufficient time interval should therefore elapse between cessation of tamoxifen and initiation of other therapeutic modalities.", "contents": "Tamoxifen-induced tumor stimulation and withdrawal response. A postmenopausal breast cancer patient with a measurable lung metastasis was treated with tamoxifen. The tumor doubling time of the pulmonary lesion was 140 days during spontaneous growth and 52 days during tamoxifen therapy, an almost threefold increase in tumor growth rate. This stimulation persisted fro 1 month after discontinuation of tamoxifen and was followed thereafter by a withdrawal regression lasting greater than 6 months. Awareness of the possible tumor growth enhancement with tamoxifen is of importance especially in view of its prolonged activity. Hormone withdrawal regression may occur following tamoxifen therapy, and a sufficient time interval should therefore elapse between cessation of tamoxifen and initiation of other therapeutic modalities."}
{"id": "PMID:230895", "title": "Therapy for hepatocellular cancer with intrahepatic arterial adriamycin and 5-fluorouracil combined with whole-liver irradiation: a Northern California Oncology Group Study.", "content": "Thirteen patients with hepatocellular cancer were treated with intrahepatic arterial Adriamycin and 5-fluorouracil combined with whole-liver irradiation. Six patients (46%) had an objective regression and five (38%) had stable disease. Symptomatic improvement was noted in 81% of the patients. The minimum median survival time was 5.0 months for those patients who responded. Toxicity was acceptable. This is an effective combination for the treatment of this especially aggressive and intractable form of cancer.", "contents": "Therapy for hepatocellular cancer with intrahepatic arterial adriamycin and 5-fluorouracil combined with whole-liver irradiation: a Northern California Oncology Group Study. Thirteen patients with hepatocellular cancer were treated with intrahepatic arterial Adriamycin and 5-fluorouracil combined with whole-liver irradiation. Six patients (46%) had an objective regression and five (38%) had stable disease. Symptomatic improvement was noted in 81% of the patients. The minimum median survival time was 5.0 months for those patients who responded. Toxicity was acceptable. This is an effective combination for the treatment of this especially aggressive and intractable form of cancer."}
{"id": "PMID:230896", "title": "Combination chemotherapy with mitomycin C, adriamycin, and cyclophosphamide in advanced adenocarcinoma and large cell carcinoma of the lung.", "content": "Thirty-six patients with advanced carcinoma of the lung (30 with adenocarcinoma and six with large cell carcinoma) were treated with a combination of mitomycin C, Adriamycin, and cyclophosphamide (MAC) in a phase II study. Seven partial remissions were observed in adenocarcinomas, while none were seen in large cell carcinomas. The survival of patients in remission was clearly prolonged (P less than 0.01), with responders living a median of at least 39 weeks compared to 17 weeks for nonresponders. The combination was well-tolerated with moderate anorexia, nausea, vomiting, and alopecia. Myelosuppression was manageable but was more pronounced in previously chemotherapeutically treated patients. MAC offers a reasonable response rate in patients with adenocarcinoma of the lung with significant prolongation of survival; however, there was no significant advantage when compared to mitomycin C used as a single agent.", "contents": "Combination chemotherapy with mitomycin C, adriamycin, and cyclophosphamide in advanced adenocarcinoma and large cell carcinoma of the lung. Thirty-six patients with advanced carcinoma of the lung (30 with adenocarcinoma and six with large cell carcinoma) were treated with a combination of mitomycin C, Adriamycin, and cyclophosphamide (MAC) in a phase II study. Seven partial remissions were observed in adenocarcinomas, while none were seen in large cell carcinomas. The survival of patients in remission was clearly prolonged (P less than 0.01), with responders living a median of at least 39 weeks compared to 17 weeks for nonresponders. The combination was well-tolerated with moderate anorexia, nausea, vomiting, and alopecia. Myelosuppression was manageable but was more pronounced in previously chemotherapeutically treated patients. MAC offers a reasonable response rate in patients with adenocarcinoma of the lung with significant prolongation of survival; however, there was no significant advantage when compared to mitomycin C used as a single agent."}
{"id": "PMID:230897", "title": "Treatment of small cell bronchogenic carcinoma with VM-26.", "content": "VM-26 is active in small cell bronchogenic carcinoma even in patients resistant to previous chemotherapy. The overall response rate was 28%, with a response rate of 29% in patients resistant to previous chemotherapy. This response rate is similar to that obtained with other single agents including Adriamycin, vincristine, cyclophosphamide, and procarbazine. The mild subjective and objective toxic effects of the drug make it a potentially useful agent in the treatment of this tumor.", "contents": "Treatment of small cell bronchogenic carcinoma with VM-26. VM-26 is active in small cell bronchogenic carcinoma even in patients resistant to previous chemotherapy. The overall response rate was 28%, with a response rate of 29% in patients resistant to previous chemotherapy. This response rate is similar to that obtained with other single agents including Adriamycin, vincristine, cyclophosphamide, and procarbazine. The mild subjective and objective toxic effects of the drug make it a potentially useful agent in the treatment of this tumor."}
{"id": "PMID:230903", "title": "Functional significance of interrenal cell zonation in the adrenal gland of the duck (Anas platyrhynchos).", "content": "Slices of whole adrenal gland tissue, incubated in vitro in the presence of ACTH for 1 h and 2 h produced corticosterone and aldosterone in constant ratio (16:1). Tangential slices taken from the region immediately below the connective tissue capsule and slices taken from deeper regions of the gland consisted primarily of cells conforming to the distinct structural characteristics of the subcapsular zone (SCZ) and inner zone (IZ) tissues respectively. When samples were incubated in the presence of ACTH for 1 h and 2 h, the interrenal cells of the SCZ produced relatively more aldosterone than cells taken from the IZ of the gland. The corticosterone: aldosterone ratio for the IZ after 1 h (68:1) and after 2 h (102:1) were ten times greater than the ratios for the SCZ after 1 h (7:1) and after 2 h (10:1). The SCZ slices were not more than 60 cells thick and consisted of cells arranged in cords. These cells contained irregular nuclei, mitochondria with shelf-like cristae and a moderate abundance of smooth endoplasmic reticulum. In contrast, the production of large amounts of corticosterone by the cells of the IZ was associated with tissue containing more vascular space than the SCZ and the cells contained large round nuclei surrounded by an abundance of smooth endoplasmic reticulum and the mitochondria had tubular rather than shelf-like cristae.", "contents": "Functional significance of interrenal cell zonation in the adrenal gland of the duck (Anas platyrhynchos). Slices of whole adrenal gland tissue, incubated in vitro in the presence of ACTH for 1 h and 2 h produced corticosterone and aldosterone in constant ratio (16:1). Tangential slices taken from the region immediately below the connective tissue capsule and slices taken from deeper regions of the gland consisted primarily of cells conforming to the distinct structural characteristics of the subcapsular zone (SCZ) and inner zone (IZ) tissues respectively. When samples were incubated in the presence of ACTH for 1 h and 2 h, the interrenal cells of the SCZ produced relatively more aldosterone than cells taken from the IZ of the gland. The corticosterone: aldosterone ratio for the IZ after 1 h (68:1) and after 2 h (102:1) were ten times greater than the ratios for the SCZ after 1 h (7:1) and after 2 h (10:1). The SCZ slices were not more than 60 cells thick and consisted of cells arranged in cords. These cells contained irregular nuclei, mitochondria with shelf-like cristae and a moderate abundance of smooth endoplasmic reticulum. In contrast, the production of large amounts of corticosterone by the cells of the IZ was associated with tissue containing more vascular space than the SCZ and the cells contained large round nuclei surrounded by an abundance of smooth endoplasmic reticulum and the mitochondria had tubular rather than shelf-like cristae."}
{"id": "PMID:230904", "title": "Neurons of the rat hypothalamus reactive with antisera against endorphins, ACTH, MSH and beta-LPH.", "content": "In rat brains intraventricularly injected with colchicine, the same discrete neurons of the arcuate and ventromedial nuclei can be stained with antisera against alpha- and beta-endorphins, (1-24)ACTH, (17-39)ACTH, alpha- and beta-MSH, and beta-LPH, as demonstrated by comparative studies in consecutive serial sections. These neurons are strongly reactive with anti-(17-39)ACTH, anti-beta-endorphin, anti-alpha-MSH and anti-beta-MSH, and more faintly stained with anti-alpha-endorphin, anti-beta-LPH and anti-(1-24)ACTH. Exceptionally, neurons reactive with anti-(17-39)ACTH and anti-beta-endorphin are poorly stained or completely negative with anti-alpha-MSH and anti-beta-MSH. Immunoreactive fibers end in the lateral median eminence and in the arcuate nucleus proper, or form ascending pathways along the third ventricle. Comparative studies with other antisera or with the Falck and Hillarp technique show that these neurons differ from the elements producing LH-RH, somatostatin, neurophysin, oxytocin, vasopressin and dopamine. These results suggest that the same neurons of the rat hypothalamus synthesize several neuropeptides identical with or immunologically related to endorphins, ACTH, alpha-MSH and beta-LPH, probably arising from a common precursor molecule similar to that found in the corticotropic cells of the pituitary. These neuropeptides of a common cellular and molecular origin might be involved in basic processes of the central nervous system as neurotramsmitters or neuromodulators.", "contents": "Neurons of the rat hypothalamus reactive with antisera against endorphins, ACTH, MSH and beta-LPH. In rat brains intraventricularly injected with colchicine, the same discrete neurons of the arcuate and ventromedial nuclei can be stained with antisera against alpha- and beta-endorphins, (1-24)ACTH, (17-39)ACTH, alpha- and beta-MSH, and beta-LPH, as demonstrated by comparative studies in consecutive serial sections. These neurons are strongly reactive with anti-(17-39)ACTH, anti-beta-endorphin, anti-alpha-MSH and anti-beta-MSH, and more faintly stained with anti-alpha-endorphin, anti-beta-LPH and anti-(1-24)ACTH. Exceptionally, neurons reactive with anti-(17-39)ACTH and anti-beta-endorphin are poorly stained or completely negative with anti-alpha-MSH and anti-beta-MSH. Immunoreactive fibers end in the lateral median eminence and in the arcuate nucleus proper, or form ascending pathways along the third ventricle. Comparative studies with other antisera or with the Falck and Hillarp technique show that these neurons differ from the elements producing LH-RH, somatostatin, neurophysin, oxytocin, vasopressin and dopamine. These results suggest that the same neurons of the rat hypothalamus synthesize several neuropeptides identical with or immunologically related to endorphins, ACTH, alpha-MSH and beta-LPH, probably arising from a common precursor molecule similar to that found in the corticotropic cells of the pituitary. These neuropeptides of a common cellular and molecular origin might be involved in basic processes of the central nervous system as neurotramsmitters or neuromodulators."}
{"id": "PMID:230905", "title": "Ultrastructural localization of immunoreactive corticotropin, beta-lipotropin, alpha- and beta-endorphin in cells of the human fetal anterior pituitary.", "content": "Cells immunoreactive with anti-alpha-(17-39) ACTH, beta-(1-24) corticotropin, beta-LPH, alpha- and beta-EP were identified in the human fetal anterior pituitary at the ultrastructural level using the peroxidase-antiperoxidase complex method on ultrathin sections. Only one definite cell type was revealed by all these antisera. All granules of each individual immunostained cell reacted regardless of the antiserum used. The immunostained cells occurred in groups and were sometimes located in the wall of the follicle-like structures commonly observed in the fetal anterior pituitary. The cells revealed two main aspects: 1) The largest elements were rich in organelles, and their numerous secretory granules showed significantly variations in size (250-500 nm in diameter), electron density of their content and stain-deposit intensity. The ergastoplasm, consisting of irregular tubules, was poorly developed. In the vicinity of the conspicuous Golgi apparatus, organelles related to the GERL complex were commonly observed. Multivesicular bodies were frequent. Some of these cells showed bundles of microfilaments (60 nm in thickness). 2) The smaller cells had an electron-lucent hyaloplasm with sparse organelles; they contained fewer granules and never showed microfilaments. The immunocytological results are consistent with the synthesis of a molecule similar to pro-opiocortin by this type of endocrine cell in human fetuses. Morphological evidence for the maturation process of this precursor and for the secretory activity of these cells and its possible regulation is presented and discussed.", "contents": "Ultrastructural localization of immunoreactive corticotropin, beta-lipotropin, alpha- and beta-endorphin in cells of the human fetal anterior pituitary. Cells immunoreactive with anti-alpha-(17-39) ACTH, beta-(1-24) corticotropin, beta-LPH, alpha- and beta-EP were identified in the human fetal anterior pituitary at the ultrastructural level using the peroxidase-antiperoxidase complex method on ultrathin sections. Only one definite cell type was revealed by all these antisera. All granules of each individual immunostained cell reacted regardless of the antiserum used. The immunostained cells occurred in groups and were sometimes located in the wall of the follicle-like structures commonly observed in the fetal anterior pituitary. The cells revealed two main aspects: 1) The largest elements were rich in organelles, and their numerous secretory granules showed significantly variations in size (250-500 nm in diameter), electron density of their content and stain-deposit intensity. The ergastoplasm, consisting of irregular tubules, was poorly developed. In the vicinity of the conspicuous Golgi apparatus, organelles related to the GERL complex were commonly observed. Multivesicular bodies were frequent. Some of these cells showed bundles of microfilaments (60 nm in thickness). 2) The smaller cells had an electron-lucent hyaloplasm with sparse organelles; they contained fewer granules and never showed microfilaments. The immunocytological results are consistent with the synthesis of a molecule similar to pro-opiocortin by this type of endocrine cell in human fetuses. Morphological evidence for the maturation process of this precursor and for the secretory activity of these cells and its possible regulation is presented and discussed."}
{"id": "PMID:230906", "title": "Ultrastructure of pinealocytes of the cotton rat, Sigmodon hispidus.", "content": "Fine structural features of pinealocytes of cotton rats (Sigmodon hispidus) were examined. Golgi complexes, mitochondria, endoplasmic reticulum and polysomes are usual organelles seen in the perikaryonal cytoplasm of pinealocytes. Many non-granulated vesicles (40 to 80 nm in diameter) and a few granulated vesicles (about 100 nm in diameter) are associated with the Golgi cisternae. Occasionally, the cisternae contain granular materials. The perikaryonal cytoplasm of pinealocytes is characterized by the presence of inclusion bodies. These bodies are usually round in shape, not bounded by a limiting membrane and composed of fine granular or filamentous materials of high electron-opacity, which are similar in appearance to the substance seen in the nucleolonema. Pinealocyte processes, filled with abundant non-granulated vesicles and some granulated vesicles, are mainly found within the parenchyma and occasionally in perivascular spaces.", "contents": "Ultrastructure of pinealocytes of the cotton rat, Sigmodon hispidus. Fine structural features of pinealocytes of cotton rats (Sigmodon hispidus) were examined. Golgi complexes, mitochondria, endoplasmic reticulum and polysomes are usual organelles seen in the perikaryonal cytoplasm of pinealocytes. Many non-granulated vesicles (40 to 80 nm in diameter) and a few granulated vesicles (about 100 nm in diameter) are associated with the Golgi cisternae. Occasionally, the cisternae contain granular materials. The perikaryonal cytoplasm of pinealocytes is characterized by the presence of inclusion bodies. These bodies are usually round in shape, not bounded by a limiting membrane and composed of fine granular or filamentous materials of high electron-opacity, which are similar in appearance to the substance seen in the nucleolonema. Pinealocyte processes, filled with abundant non-granulated vesicles and some granulated vesicles, are mainly found within the parenchyma and occasionally in perivascular spaces."}
{"id": "PMID:230907", "title": "Polarity of three-dimensional structures derived from isolated hog thyroid cells in primary culture.", "content": "When cultured in polystyrene dishes subjected to previous treatment and supplied with a serum-containing medium, hog thyroid cells form monolayers displaying dome-like arrangements after three to four days. Cells involved in formation of \"domes\" are morphologically polarized; the apical microvilli of these cells point toward the culture medium. When the tissue is cultured in untreated polystyrene dishes, thyroid cells remain in suspension; their aggregates swell progressively and form hollow spheres encompassed by a single layer of cells. The polarity of the cells forming such spheres is inverse in comparison to the condition characteristic of the intact thyroid gland. When culture medium is supplemented with TSH, PGE1, PGE2 or dBC, structures resembling true follicles are formed in both types of cultures. Gelatin, added to suspension cultures, is also capable of promoting follicle formation. Cultured thyroid cells regularly form an epithelial layer as a result of the interaction of cellular processes. However, the polarization of this layer depends on culture conditions. Thus, structures with either a normal follicle-like polarization of their cells or showing an inverted type of polarization can be obtained.", "contents": "Polarity of three-dimensional structures derived from isolated hog thyroid cells in primary culture. When cultured in polystyrene dishes subjected to previous treatment and supplied with a serum-containing medium, hog thyroid cells form monolayers displaying dome-like arrangements after three to four days. Cells involved in formation of \"domes\" are morphologically polarized; the apical microvilli of these cells point toward the culture medium. When the tissue is cultured in untreated polystyrene dishes, thyroid cells remain in suspension; their aggregates swell progressively and form hollow spheres encompassed by a single layer of cells. The polarity of the cells forming such spheres is inverse in comparison to the condition characteristic of the intact thyroid gland. When culture medium is supplemented with TSH, PGE1, PGE2 or dBC, structures resembling true follicles are formed in both types of cultures. Gelatin, added to suspension cultures, is also capable of promoting follicle formation. Cultured thyroid cells regularly form an epithelial layer as a result of the interaction of cellular processes. However, the polarization of this layer depends on culture conditions. Thus, structures with either a normal follicle-like polarization of their cells or showing an inverted type of polarization can be obtained."}
{"id": "PMID:230916", "title": "[Neuronal activity specific to paradoxical sleep in the bulbar reticular formation in the unrestrained cat].", "content": "Single units were recorded in the bulbar reticular formation (BRF) of unrestrained, freely behaving Cats. In the ventromedial part of the BRF (n. reticularis magnocellularis, Mc) corresponding to the \"bulbar inhibitory center\", we have found a cluster of cells showing tonic activation highly selective to paradoxical sleep (PS). Furthermore, we have confirmed the presence of the same type of cells in the dorsomedial part of the BRF which corresponds to the medial part of the n. reticularis parvocellularis (Pc). The functional significance of these two groups of cells is discussed in terms of the postural atonia and the atonia of jaw closer muscles observed during PS.", "contents": "[Neuronal activity specific to paradoxical sleep in the bulbar reticular formation in the unrestrained cat]. Single units were recorded in the bulbar reticular formation (BRF) of unrestrained, freely behaving Cats. In the ventromedial part of the BRF (n. reticularis magnocellularis, Mc) corresponding to the \"bulbar inhibitory center\", we have found a cluster of cells showing tonic activation highly selective to paradoxical sleep (PS). Furthermore, we have confirmed the presence of the same type of cells in the dorsomedial part of the BRF which corresponds to the medial part of the n. reticularis parvocellularis (Pc). The functional significance of these two groups of cells is discussed in terms of the postural atonia and the atonia of jaw closer muscles observed during PS."}
{"id": "PMID:230917", "title": "Active and inactive renin in normal human plasma. Comparison between acid activation and cryoactivation.", "content": "Inactive renin in human plasma is converted to active renin in vitro by acid activation or by cryoactivation. Renin activity was measured at pH 5.5 and renin concentration at pH 7.4. The plasma renin activity before and after cryo-treatment is termed active (APRA) and total (TPRA) plasma renin activity; the plasma renin concentration before and after acid treatment active (APRC) and total (TPRC) plasma renin concentration. In this study we demonstrated that in normal subjects the proportion of active to total renin after cryo-treatment averaged 61%, which was significantly (p less than 0.001) higher than the mean percentage active renin of 34 found with the acid activation procedure. Plasma angiotensin II correlated significantly with APRA, TPRA, TPRC and plasma angiotensin I (PA I), but not with inactive renin, which suggests that inactive renin does not produce angiotensin II in vivo. Cold treatment after acid activation and acid treatment after cryoactivation did not provoke a significant change in the measured renin concentration. Our data support the view that acidification of the plasma activates more than does cryo-treatment, and that inactive renin does not contribute to plasma angiotensin II.", "contents": "Active and inactive renin in normal human plasma. Comparison between acid activation and cryoactivation. Inactive renin in human plasma is converted to active renin in vitro by acid activation or by cryoactivation. Renin activity was measured at pH 5.5 and renin concentration at pH 7.4. The plasma renin activity before and after cryo-treatment is termed active (APRA) and total (TPRA) plasma renin activity; the plasma renin concentration before and after acid treatment active (APRC) and total (TPRC) plasma renin concentration. In this study we demonstrated that in normal subjects the proportion of active to total renin after cryo-treatment averaged 61%, which was significantly (p less than 0.001) higher than the mean percentage active renin of 34 found with the acid activation procedure. Plasma angiotensin II correlated significantly with APRA, TPRA, TPRC and plasma angiotensin I (PA I), but not with inactive renin, which suggests that inactive renin does not produce angiotensin II in vivo. Cold treatment after acid activation and acid treatment after cryoactivation did not provoke a significant change in the measured renin concentration. Our data support the view that acidification of the plasma activates more than does cryo-treatment, and that inactive renin does not contribute to plasma angiotensin II."}
{"id": "PMID:230914", "title": "[Coprologic diagnosis of amebiasis : the rectocolitis cell trap and the value of cultures].", "content": "The authors give the differential characters of dysenteric amoebae and cells observed in the feaces of patients affected by recto-colitis. In this purpose, they recall the usefullness of cultures for both the presence and the possibility of determination of the Amoebae. In short, they deplore the misappreciation of these advantages.", "contents": "[Coprologic diagnosis of amebiasis : the rectocolitis cell trap and the value of cultures]. The authors give the differential characters of dysenteric amoebae and cells observed in the feaces of patients affected by recto-colitis. In this purpose, they recall the usefullness of cultures for both the presence and the possibility of determination of the Amoebae. In short, they deplore the misappreciation of these advantages."}
{"id": "PMID:230918", "title": "Values of APO-1 and APO-B in humans according to age and sex.", "content": "Two series of 100 subjects each, males and females, have been studied for the determination of plasma values of apo-A1, the major peptide of HDL, and of apo-B, the major peptide of LDL. To minimize a possible influence of variations in plasma lipid levels, two series of subjects were selected with very similar mean values of plasma cholesterol and triglyceride. Despite this criterion of selection apo-A1 was significantly lower in males (127 +/- 18 mg/l) than in females (137 +/- 15 mg/l) while the reverse was true for apo-B (99 +/- 16 mg/l in males vs. 91 +/- mg/l in females). Both apo-B and apo-A1 showed a tendency to increase with advancing age with the greatest increase for apo-A1 (in both sexes) and for apo-B (only in males) from the 3rd to the 4th decade of age.", "contents": "Values of APO-1 and APO-B in humans according to age and sex. Two series of 100 subjects each, males and females, have been studied for the determination of plasma values of apo-A1, the major peptide of HDL, and of apo-B, the major peptide of LDL. To minimize a possible influence of variations in plasma lipid levels, two series of subjects were selected with very similar mean values of plasma cholesterol and triglyceride. Despite this criterion of selection apo-A1 was significantly lower in males (127 +/- 18 mg/l) than in females (137 +/- 15 mg/l) while the reverse was true for apo-B (99 +/- 16 mg/l in males vs. 91 +/- mg/l in females). Both apo-B and apo-A1 showed a tendency to increase with advancing age with the greatest increase for apo-A1 (in both sexes) and for apo-B (only in males) from the 3rd to the 4th decade of age."}
{"id": "PMID:230919", "title": "Determination of cholesterol and phospholipid concentrations in high-density lipoproteins by heparin-manganese chloride precipitation.", "content": "Cholesterol as well as phospholipids in high-density lipoproteins (HDL) have been measured in 60 serum samples after heparin-manganese chloride precipitation of the apolipoprotein B containing lipoproteins. The values obtained correlated well with values from ultracentrifugal separation (slope 1.11 for cholesterol, 0.92 for phospholipids). Furthermore, there was a significant correlation between the low-density lipoprotein (LDL) cholesterol estimated by the formula of Friedewald et al. and the ultracentrifugally separated LDL cholesterol (slope 1.02). By the additional determination of HDL phospholipids with a precipitation procedure, further information about the \"antiatherogenic\" is easily available.", "contents": "Determination of cholesterol and phospholipid concentrations in high-density lipoproteins by heparin-manganese chloride precipitation. Cholesterol as well as phospholipids in high-density lipoproteins (HDL) have been measured in 60 serum samples after heparin-manganese chloride precipitation of the apolipoprotein B containing lipoproteins. The values obtained correlated well with values from ultracentrifugal separation (slope 1.11 for cholesterol, 0.92 for phospholipids). Furthermore, there was a significant correlation between the low-density lipoprotein (LDL) cholesterol estimated by the formula of Friedewald et al. and the ultracentrifugally separated LDL cholesterol (slope 1.02). By the additional determination of HDL phospholipids with a precipitation procedure, further information about the \"antiatherogenic\" is easily available."}
{"id": "PMID:230925", "title": "Evaluation of functional thymic hormones in Arabian horses with severe combined immunodeficiency.", "content": "Arabian horses with severe combined immunodeficiency disease (SCID) were evaluated for thymic hormone activities using thymic extracts and sera. Extracts prepared from thymus of SCID horses were able to increase the number of spleen cells responding to sheep red blood cells in irradiated, bone marrow-reconstituted mice. In addition, ultrafiltrates prepared from sera of these immunodeficient horses, which contained material with molecular weight of less than 50,000 Daltons could (a) induce a population of human bone marrow precursor cells to differentiate into cells bearing SRBC receptors and form spontaneous E-rosettes, a characteristic of T lymphocytes, and (b) stimulate cyclic adenosine monophosphate (AMP) synthesis in mouse thymocytes. Based on in vivo and in vitro effects, it was concluded that the defect of these Arabian horses with severe combined immunodeficiency disease did not involve a complete thymic hormone inadequacy.", "contents": "Evaluation of functional thymic hormones in Arabian horses with severe combined immunodeficiency. Arabian horses with severe combined immunodeficiency disease (SCID) were evaluated for thymic hormone activities using thymic extracts and sera. Extracts prepared from thymus of SCID horses were able to increase the number of spleen cells responding to sheep red blood cells in irradiated, bone marrow-reconstituted mice. In addition, ultrafiltrates prepared from sera of these immunodeficient horses, which contained material with molecular weight of less than 50,000 Daltons could (a) induce a population of human bone marrow precursor cells to differentiate into cells bearing SRBC receptors and form spontaneous E-rosettes, a characteristic of T lymphocytes, and (b) stimulate cyclic adenosine monophosphate (AMP) synthesis in mouse thymocytes. Based on in vivo and in vitro effects, it was concluded that the defect of these Arabian horses with severe combined immunodeficiency disease did not involve a complete thymic hormone inadequacy."}
{"id": "PMID:230926", "title": "Lymphocyte activation induced by Trichinella spiralis infection reflected as spontaneous DNA synthesis in vitro.", "content": "Spleen cells from mice, infected with Trichinella spiralis, were cultured in micro and macrocultures without stimulatory agents. As controls, various polyclonal T and B cell activators were used. During the course of the infection the cells exhibited an increased spontaneous DNA synthesis compared to the cells from uninfected controls. It was also found that the relative proportion of theta and Ig-positive cells and macrophages was not significantly affected by the infection. To characterize the in vivo stimulated cells one week after infection various techniques were used. Autoradiography combined with immunofluorescence revealed that virtually all labelled cells were Ig-negative. Removal of macrophages by silica powder decreased the spontaneous DNA synthesis but not to the level of the controls. Spleen cells from infected nude mice did not show any increased spontaneous DNA synthesis, whereas the effluent cells obtained after separation on Ig-complexed columns still showed an enhanced spontaneous DNA synthesis. These results indicate that T. spiralis infection causes a macrophage dependent activation of T cells which in vitro is detectable as spontaneous DNA synthesis.", "contents": "Lymphocyte activation induced by Trichinella spiralis infection reflected as spontaneous DNA synthesis in vitro. Spleen cells from mice, infected with Trichinella spiralis, were cultured in micro and macrocultures without stimulatory agents. As controls, various polyclonal T and B cell activators were used. During the course of the infection the cells exhibited an increased spontaneous DNA synthesis compared to the cells from uninfected controls. It was also found that the relative proportion of theta and Ig-positive cells and macrophages was not significantly affected by the infection. To characterize the in vivo stimulated cells one week after infection various techniques were used. Autoradiography combined with immunofluorescence revealed that virtually all labelled cells were Ig-negative. Removal of macrophages by silica powder decreased the spontaneous DNA synthesis but not to the level of the controls. Spleen cells from infected nude mice did not show any increased spontaneous DNA synthesis, whereas the effluent cells obtained after separation on Ig-complexed columns still showed an enhanced spontaneous DNA synthesis. These results indicate that T. spiralis infection causes a macrophage dependent activation of T cells which in vitro is detectable as spontaneous DNA synthesis."}
{"id": "PMID:230927", "title": "Effects of clofibrate on plasma lipids and high-density lipoprotein levels in renal allograft recipients.", "content": "Thirteen successfully transplanted renal patients with normal and elevated plasma lipids were treated as out-patients for two-month intervals with placebo and clofibrate (2 g/day) and whole plasma and lipoprotein triglyceride and cholesterol concentrations were measured. With clofibrate treatment, plasma triglyceride (194 +/- 11 to 157 +/- 10 mg/100 ml; P less than .01) and cholesterol (242 +/- 8 to 212 +/- 8 mg/100 ml; P less than .002) concentrations both decreased significantly despite the continued administration of stable immunosuppressive doses of prednisolone. While the absolute changes in cholesterol in the low and high-density lipoprotein classes varied considerably following clofibrate administration, the ratio of cholesterol in the low and high-density lipoproteins fell from 3.8 to 3.3. This theoretically beneficial anti-atherogenic effect was significant (P less than .01) in male allograft recipients only. These findings indicate that clofibrate treatment favorably influences the cardiovascular risk posed by both qualitative and quantitative disturbances in lipoprotein transport following successful renal allografting.", "contents": "Effects of clofibrate on plasma lipids and high-density lipoprotein levels in renal allograft recipients. Thirteen successfully transplanted renal patients with normal and elevated plasma lipids were treated as out-patients for two-month intervals with placebo and clofibrate (2 g/day) and whole plasma and lipoprotein triglyceride and cholesterol concentrations were measured. With clofibrate treatment, plasma triglyceride (194 +/- 11 to 157 +/- 10 mg/100 ml; P less than .01) and cholesterol (242 +/- 8 to 212 +/- 8 mg/100 ml; P less than .002) concentrations both decreased significantly despite the continued administration of stable immunosuppressive doses of prednisolone. While the absolute changes in cholesterol in the low and high-density lipoprotein classes varied considerably following clofibrate administration, the ratio of cholesterol in the low and high-density lipoproteins fell from 3.8 to 3.3. This theoretically beneficial anti-atherogenic effect was significant (P less than .01) in male allograft recipients only. These findings indicate that clofibrate treatment favorably influences the cardiovascular risk posed by both qualitative and quantitative disturbances in lipoprotein transport following successful renal allografting."}
{"id": "PMID:230929", "title": "Emotional responses to subcortical electrical stimulation in psychiatric patients.", "content": "Subcortical electrical stimulation was applied to the prospective surgical target area during 158 stereotactic operations in 135 psychiatric patients. The following target areas were studied: rostral cingulum below and in front of the genu of the corpus callosum (52 cases) genu (46) cingululum just above the genu (11) middle cingulum (6) anterior internal capsule (33) subcaudate region, 'substantia innominata' (10 cases). Forty-seven per cent of the cases reacted to stimulation with subjective emotional sensory responses. Stimulation of differ targets had significantly different results. Responses were obtained most frequently from the cingulum and genu, and least frequently from the anterior capsule and subcaudate regions. Stimulation of the rostral cingulum often caused 'negative' responses, i.e. an increase in or the appearance of anxiety and tension (11/15 cases). The opposite was true of the adjacent genu of the corpus callosum; on stimulation of this structure anxiety and tension disappeared or diminished (18/19 cases). Schizophrenic patients experienced such 'positive' responses significantly more often than non-schizophrenics. In non-anesthetized patients autonomic reactions were very rare.", "contents": "Emotional responses to subcortical electrical stimulation in psychiatric patients. Subcortical electrical stimulation was applied to the prospective surgical target area during 158 stereotactic operations in 135 psychiatric patients. The following target areas were studied: rostral cingulum below and in front of the genu of the corpus callosum (52 cases) genu (46) cingululum just above the genu (11) middle cingulum (6) anterior internal capsule (33) subcaudate region, 'substantia innominata' (10 cases). Forty-seven per cent of the cases reacted to stimulation with subjective emotional sensory responses. Stimulation of differ targets had significantly different results. Responses were obtained most frequently from the cingulum and genu, and least frequently from the anterior capsule and subcaudate regions. Stimulation of the rostral cingulum often caused 'negative' responses, i.e. an increase in or the appearance of anxiety and tension (11/15 cases). The opposite was true of the adjacent genu of the corpus callosum; on stimulation of this structure anxiety and tension disappeared or diminished (18/19 cases). Schizophrenic patients experienced such 'positive' responses significantly more often than non-schizophrenics. In non-anesthetized patients autonomic reactions were very rare."}
{"id": "PMID:230930", "title": "Distinction between benign and malignant type of Parkinson's disease.", "content": "Clinical data demonstrate that there is a significant difference between at least two types of idiopathic Parkinsonian patients; a benign type of Parkinson's disease and a malignant type. They can be distinguished by the time course of a disability-score, independent of the duration of the disease. The benign cases respond very well to L-Dopa (Madopar) treatment and show a long lasting (7 years) drop in the disability, whereas the improvement of disability in the malignant cases is much smaller and lasts for about one year, followed by an increase of disability. The duration of the disease is 12,5 +/- 0,4 years in the benign type but only 4,0 +/- 0,3 years in the malignant type. Akinetic crises, off-phases, hyperkinetic crises and toxic deliria after Madopar treatment can be observed later in the benign than in the malignant cases. These results suggest that the degeneration of the dopaminergic nigrostriatal system occurs much more rapidly in malignant cases than in benign cases of Parkinson's disease.", "contents": "Distinction between benign and malignant type of Parkinson's disease. Clinical data demonstrate that there is a significant difference between at least two types of idiopathic Parkinsonian patients; a benign type of Parkinson's disease and a malignant type. They can be distinguished by the time course of a disability-score, independent of the duration of the disease. The benign cases respond very well to L-Dopa (Madopar) treatment and show a long lasting (7 years) drop in the disability, whereas the improvement of disability in the malignant cases is much smaller and lasts for about one year, followed by an increase of disability. The duration of the disease is 12,5 +/- 0,4 years in the benign type but only 4,0 +/- 0,3 years in the malignant type. Akinetic crises, off-phases, hyperkinetic crises and toxic deliria after Madopar treatment can be observed later in the benign than in the malignant cases. These results suggest that the degeneration of the dopaminergic nigrostriatal system occurs much more rapidly in malignant cases than in benign cases of Parkinson's disease."}
{"id": "PMID:230931", "title": "A peculiar brain scan pattern in necrotizing leukoencephalopathy after treatment for CNS-leukaemia.", "content": "Two patients with CNS-leukaemia who developed a leukoencephalopathy after cranial irradiation and methotrexate administration are described. Conventional brain scanning with 99m TC-pertechnetate showed a peculiar pattern which suggested the presence of radio-activity within enlarged ventricles, but were later interpreted as accumulation in the periventricular white matter. The brainscan pattern correlated well with the neuropathological findings in the case where autopsy was performed. This brain scan pattern is for unknown reasons only rarely mentioned in literature. It seems a useful tool in diagnostic procedures in similar patients.", "contents": "A peculiar brain scan pattern in necrotizing leukoencephalopathy after treatment for CNS-leukaemia. Two patients with CNS-leukaemia who developed a leukoencephalopathy after cranial irradiation and methotrexate administration are described. Conventional brain scanning with 99m TC-pertechnetate showed a peculiar pattern which suggested the presence of radio-activity within enlarged ventricles, but were later interpreted as accumulation in the periventricular white matter. The brainscan pattern correlated well with the neuropathological findings in the case where autopsy was performed. This brain scan pattern is for unknown reasons only rarely mentioned in literature. It seems a useful tool in diagnostic procedures in similar patients."}
{"id": "PMID:230932", "title": "Primary intracranial malignant lymphomas a fine structural cytochemical and CSF immunological study.", "content": "Cytochemical and electron microscopical studies in six cases of primary intracranial malignant lymphomas, four of which were diagnosed by biopsy, confirmed their ultrastructural identity with extraneural malignant lymphomas classified as immunoblastomas and immunocytomas. Demonstration of transformation of 'blast-like' cells (immunoblasts) toward rough E. R. developing cells in all these tumours argue for the B-dell origin of these types of cerebral lymphomas, previously referred to as reticulum cell sarcomas/microgliomas. CSF studies showed increased levels of B cells with surface IgG in two cases of immunoblastoma, and increased IgG levels with light chains in two cases each immunoblastoma and of pleomorphic immunocytoma, while one case of immunoblastoma showed a normal T cell to B cell ratio with increased monoclonal and surface, IgM suggesting some morphological and immunological heterogeneity of these lymphomas.", "contents": "Primary intracranial malignant lymphomas a fine structural cytochemical and CSF immunological study. Cytochemical and electron microscopical studies in six cases of primary intracranial malignant lymphomas, four of which were diagnosed by biopsy, confirmed their ultrastructural identity with extraneural malignant lymphomas classified as immunoblastomas and immunocytomas. Demonstration of transformation of 'blast-like' cells (immunoblasts) toward rough E. R. developing cells in all these tumours argue for the B-dell origin of these types of cerebral lymphomas, previously referred to as reticulum cell sarcomas/microgliomas. CSF studies showed increased levels of B cells with surface IgG in two cases of immunoblastoma, and increased IgG levels with light chains in two cases each immunoblastoma and of pleomorphic immunocytoma, while one case of immunoblastoma showed a normal T cell to B cell ratio with increased monoclonal and surface, IgM suggesting some morphological and immunological heterogeneity of these lymphomas."}
{"id": "PMID:230933", "title": "Auditory brainstem evoked responses in brainstem compression due to posterior fossa tumors.", "content": "Five patients with unilateral posterior fossa tumors were investigated with Auditory Brainstem Evoked Responses (B.E.R.). The B.E.R., recorded from the ear ipsilateral to the tumor, were consistent with a lesion of the acoustic nerve or the cochlear nuclei in all patients. The contralaterally evoked responses in four patients with large tumors and radiological signs of brainstem compression showed normal latencies and amplitudes of the first three waves, while waves IV and V were definitely abnormal with respect to amplitudes and latencies. (The 4th patient had a normal wave IV and a delayed, small wave V). In one patient with a relatively small acoustic neurinoma the contralateral B.E.R. were normal. It is concluded that the upper pontine and lower midbrain level, presumed sites of generation of wave IV and V of the B.E.R., are more susceptible to brainstem compression due to unilateral posterior fossa tumors, than the lower parts of the brainstem.", "contents": "Auditory brainstem evoked responses in brainstem compression due to posterior fossa tumors. Five patients with unilateral posterior fossa tumors were investigated with Auditory Brainstem Evoked Responses (B.E.R.). The B.E.R., recorded from the ear ipsilateral to the tumor, were consistent with a lesion of the acoustic nerve or the cochlear nuclei in all patients. The contralaterally evoked responses in four patients with large tumors and radiological signs of brainstem compression showed normal latencies and amplitudes of the first three waves, while waves IV and V were definitely abnormal with respect to amplitudes and latencies. (The 4th patient had a normal wave IV and a delayed, small wave V). In one patient with a relatively small acoustic neurinoma the contralateral B.E.R. were normal. It is concluded that the upper pontine and lower midbrain level, presumed sites of generation of wave IV and V of the B.E.R., are more susceptible to brainstem compression due to unilateral posterior fossa tumors, than the lower parts of the brainstem."}
{"id": "PMID:230934", "title": "Collateral circulation and stealmechanisms in innominate and subclavian artery obstruction.", "content": "Various types of collateral circulation and of intra- and extracerebral stealmechanisms have been described during the past two decades. The object of this short report is to discuss the clinical-angiographic data of two patients with extracranial cerebro-vascular occlusion, also in relation with current literature. Two case histories are described. The first showed a double extracerebral steal plus intracerebral interhemispheric steal, due to innominate artery obstruction. The second had only a external vertebral collateral circulation due to proximal subclavian occlusion. The factors which precipitate collateral circulation to steal are discussed.", "contents": "Collateral circulation and stealmechanisms in innominate and subclavian artery obstruction. Various types of collateral circulation and of intra- and extracerebral stealmechanisms have been described during the past two decades. The object of this short report is to discuss the clinical-angiographic data of two patients with extracranial cerebro-vascular occlusion, also in relation with current literature. Two case histories are described. The first showed a double extracerebral steal plus intracerebral interhemispheric steal, due to innominate artery obstruction. The second had only a external vertebral collateral circulation due to proximal subclavian occlusion. The factors which precipitate collateral circulation to steal are discussed."}
{"id": "PMID:230935", "title": "Extracranial CSF shunting for infantile non tumoral hydrocephalus--a retrospective analysis of 360 cases.", "content": "A series of 360 consecutive extracranial CSF shunts performed between June 1960 and June 1976 for infantile non tumoral hydrocephalus is reviewed. The surgical methods used, the reasons for re-operation, the time distribution of post-operative complications, the causes of death and the long term results are analysed and discussed for each of the four groups: tetraventricular communicating hydrocephalus, triventricular hydrocephalus, obstructive hydrocephalus with a ventriculo-cisternal block and post-meningocele or post-myelomeningocele hydrocephalus.", "contents": "Extracranial CSF shunting for infantile non tumoral hydrocephalus--a retrospective analysis of 360 cases. A series of 360 consecutive extracranial CSF shunts performed between June 1960 and June 1976 for infantile non tumoral hydrocephalus is reviewed. The surgical methods used, the reasons for re-operation, the time distribution of post-operative complications, the causes of death and the long term results are analysed and discussed for each of the four groups: tetraventricular communicating hydrocephalus, triventricular hydrocephalus, obstructive hydrocephalus with a ventriculo-cisternal block and post-meningocele or post-myelomeningocele hydrocephalus."}
{"id": "PMID:230938", "title": "Ascorbic acid deficiency and hypertrophic osteodystrophy in the dog: a rebuttal.", "content": "Plasma ascorbic acid (PAA) in normal Labrador Retriever dogs less than one year of age averaged 1.22 +/- 0.05 mg/dl (x +/- sem) and was significantly higher than the value of 0.89 +/- 0.03, for Labrador Retrievers two years of age and older. No significant diurnal variation in PAA was observed. Oral or intravenous administration of 0.5 or 1.0 g of ascorbic acid (AA) elevated PAA for less than 8 hours. Injection of ACTH caused a significant decline in PAA for the initial 2 days, with variable results thereafter. Labrador Retriever puppies fed a ration high in protein, energy and calcium developed the typical skeletal diseases of overnutrition, including hypertrophic osteodystrophy (HOD). The addition or oral AA (0.5 g twice daily) had no ameliorating effect on the skeletal lesions. Instead AA supplementation resulted in relatively higher serum calcium values which, presumably by enhanced hypercalcitoninism, decreased bone resorption. Thus, AA treatment of dogs with HOD is contraindicated, as it can only aggravate the osseous lesions of HOD. The decreased PAA reported in dogs with HOD is interpreted to be the result of stress from pain.", "contents": "Ascorbic acid deficiency and hypertrophic osteodystrophy in the dog: a rebuttal. Plasma ascorbic acid (PAA) in normal Labrador Retriever dogs less than one year of age averaged 1.22 +/- 0.05 mg/dl (x +/- sem) and was significantly higher than the value of 0.89 +/- 0.03, for Labrador Retrievers two years of age and older. No significant diurnal variation in PAA was observed. Oral or intravenous administration of 0.5 or 1.0 g of ascorbic acid (AA) elevated PAA for less than 8 hours. Injection of ACTH caused a significant decline in PAA for the initial 2 days, with variable results thereafter. Labrador Retriever puppies fed a ration high in protein, energy and calcium developed the typical skeletal diseases of overnutrition, including hypertrophic osteodystrophy (HOD). The addition or oral AA (0.5 g twice daily) had no ameliorating effect on the skeletal lesions. Instead AA supplementation resulted in relatively higher serum calcium values which, presumably by enhanced hypercalcitoninism, decreased bone resorption. Thus, AA treatment of dogs with HOD is contraindicated, as it can only aggravate the osseous lesions of HOD. The decreased PAA reported in dogs with HOD is interpreted to be the result of stress from pain."}
{"id": "PMID:230939", "title": "Evaluation of sodium stibogluconate in the treatment of cutaneous leishmaniasis in Syria.", "content": "A series of 31 patients presenting with skin lesions with positive smears for leishmania parasites were treated with sodium stibogluconate (each ml of injection containing the equivalent of 100 mg pentavalent antimony). The drug was administered either intramuscularly at a dosage of 6 ml daily for at least 10 days or infiltrated around the lesion (maximum 2 ml per lesion) at weekly intervals for 3 to 4 consecutive weeks. Twenty-four (77%) of the patients were assessed as showing a successful response, with parasites absent from the smear and the lesions healing at the end of treatment. Poor results, however, were reported in 5 of the 16 patients treated solely by infiltration. Follow-up of a few patients at 3 months showed that the healing process was prompt and little disfiguration was produced, lesions on the trunk tending to heal more quickly than those on the face.", "contents": "Evaluation of sodium stibogluconate in the treatment of cutaneous leishmaniasis in Syria. A series of 31 patients presenting with skin lesions with positive smears for leishmania parasites were treated with sodium stibogluconate (each ml of injection containing the equivalent of 100 mg pentavalent antimony). The drug was administered either intramuscularly at a dosage of 6 ml daily for at least 10 days or infiltrated around the lesion (maximum 2 ml per lesion) at weekly intervals for 3 to 4 consecutive weeks. Twenty-four (77%) of the patients were assessed as showing a successful response, with parasites absent from the smear and the lesions healing at the end of treatment. Poor results, however, were reported in 5 of the 16 patients treated solely by infiltration. Follow-up of a few patients at 3 months showed that the healing process was prompt and little disfiguration was produced, lesions on the trunk tending to heal more quickly than those on the face."}
{"id": "PMID:230941", "title": "Vitamin D-resistant rickets. A prototype of nutritional management of a genetic disorder.", "content": "The discovery of the vitamin D endocrine system has opened up many possibilities in our understanding of metabolic bone disease. Of particular importance is the fact that we can now manage certain genetic disorders resulting in vitamin D-resistant rickets or vitamin D-resistant hypocalcemia with the new active hormonal forms of vitamin D and with intelligent dietary management to provide for correction of the mineral difficulty. Thus, in the case of vitamin D dependency, replacement need only be with the missing hormone, 1,25-(OH)2D3. On the other hand, familial hypophosphatemia requires adjustment of the plasma phosphorus by frequent administration of oral phosphate and the adjustment of intestinal calcium absorption by 1,25-(OH)2D3. Renal failure patients require the adjustment of plasma phosphorus concentration and parathyroid hormone status, and the administration of the missing hormone 1,25-(OH)2D3. Hypoparathyroid patients require oral calcium plus 1,25-(OH)2D3, and premature infants require administration of the 1,25-(OH)2D3 because the immature kidneys and immature parathyroid glands fail to produce the required amount of this hormone. Other vitamin D-resistant rachitic conditions cannot be discussed here for lack of space and for lack of information. Undoubtedly, such patients as those having rickets secondary to renal tubular acidosis and rickets secondary to hepatic disorders will eventually come under effecti dietary and hormonal management. In this sense, the vitamin D endocrine system and vitamin D-resistant rickets can serve as a prototype of management of a genetic disorder by dietary means.", "contents": "Vitamin D-resistant rickets. A prototype of nutritional management of a genetic disorder. The discovery of the vitamin D endocrine system has opened up many possibilities in our understanding of metabolic bone disease. Of particular importance is the fact that we can now manage certain genetic disorders resulting in vitamin D-resistant rickets or vitamin D-resistant hypocalcemia with the new active hormonal forms of vitamin D and with intelligent dietary management to provide for correction of the mineral difficulty. Thus, in the case of vitamin D dependency, replacement need only be with the missing hormone, 1,25-(OH)2D3. On the other hand, familial hypophosphatemia requires adjustment of the plasma phosphorus by frequent administration of oral phosphate and the adjustment of intestinal calcium absorption by 1,25-(OH)2D3. Renal failure patients require the adjustment of plasma phosphorus concentration and parathyroid hormone status, and the administration of the missing hormone 1,25-(OH)2D3. Hypoparathyroid patients require oral calcium plus 1,25-(OH)2D3, and premature infants require administration of the 1,25-(OH)2D3 because the immature kidneys and immature parathyroid glands fail to produce the required amount of this hormone. Other vitamin D-resistant rachitic conditions cannot be discussed here for lack of space and for lack of information. Undoubtedly, such patients as those having rickets secondary to renal tubular acidosis and rickets secondary to hepatic disorders will eventually come under effecti dietary and hormonal management. In this sense, the vitamin D endocrine system and vitamin D-resistant rickets can serve as a prototype of management of a genetic disorder by dietary means."}
{"id": "PMID:230944", "title": "Assessing the need for follow-up: the relationship of prognosis to posthospitalization adjustment.", "content": "Parents of children (N-64) hospitalized at a psychiatric hospital between the years 1971 and 1976 rated their child's adjustment in a number of behavioral areas. Problems in school, making friends, acting age-appropriately, and handling aggression were reported to be the major sources of difficulty for 40% of the former patients. No statistical relationship was found between clinicians' prognosis at discharge and children's post-hospitalization adjustment. The authors discuss some of the variables that mitigate against accurate outcome prediction and argue for the integration of an organized follow-up program into their treatment program.", "contents": "Assessing the need for follow-up: the relationship of prognosis to posthospitalization adjustment. Parents of children (N-64) hospitalized at a psychiatric hospital between the years 1971 and 1976 rated their child's adjustment in a number of behavioral areas. Problems in school, making friends, acting age-appropriately, and handling aggression were reported to be the major sources of difficulty for 40% of the former patients. No statistical relationship was found between clinicians' prognosis at discharge and children's post-hospitalization adjustment. The authors discuss some of the variables that mitigate against accurate outcome prediction and argue for the integration of an organized follow-up program into their treatment program."}
{"id": "PMID:230946", "title": "Some unusual complications of myelography and lumbosacral radiculography.", "content": "In 570 patients an examination of the subarachnoideal space was performed. In 77 of them oily contrast media, in 93 oxygen and in the remaining 400 patients different water-soluble contrast media were used, including Conray 60, Dimer X and Amipaque. Neurotoxic spinal complications occurred in 12 of the 400 patients investigated with hydrosoluble agents (i.e. in 3%). In one of them after investigation with Dimer X, intense cramps in the lower extremities caused a fracture of the femoral neck within a few hours after the investigation. In another patient, investigated with Amipaque, a psychotic reaction with amentia and paranoid symptoms developed, which disappeared completely after 4 days.", "contents": "Some unusual complications of myelography and lumbosacral radiculography. In 570 patients an examination of the subarachnoideal space was performed. In 77 of them oily contrast media, in 93 oxygen and in the remaining 400 patients different water-soluble contrast media were used, including Conray 60, Dimer X and Amipaque. Neurotoxic spinal complications occurred in 12 of the 400 patients investigated with hydrosoluble agents (i.e. in 3%). In one of them after investigation with Dimer X, intense cramps in the lower extremities caused a fracture of the femoral neck within a few hours after the investigation. In another patient, investigated with Amipaque, a psychotic reaction with amentia and paranoid symptoms developed, which disappeared completely after 4 days."}
{"id": "PMID:230949", "title": "Cyclic nucleotides and ethanol tolerance and dependence.", "content": "Acute ethanol administration decreases cyclic AMP levels in brains of some animal strains. The ethanol-induced decrease of cyclic GMP levels cannot be blocked by intraventricular infusion of calcium but it can be prevented by pretreatment with pyrazole. Although cyclic AMP levels in the cerebral cortex change reciprocally after acute ethanol administration and during withdrawal, the increase observed during withdrawal is probably secondary to some withdrawal processes. Ethanol decreases cerebellar GABA levels only in rats which are stressed prior to sacrifice. Chronic intraventricular infusion of calcium increased the intensity of an acoustic startle response during ethanol withdrawal while EGTA infusion delayed the development of tolerance to the hypothermic effect of ethanol. The ratio of cyclic GMP to GABA levels is postulated to be important for expression of the withdrawal syndrome.", "contents": "Cyclic nucleotides and ethanol tolerance and dependence. Acute ethanol administration decreases cyclic AMP levels in brains of some animal strains. The ethanol-induced decrease of cyclic GMP levels cannot be blocked by intraventricular infusion of calcium but it can be prevented by pretreatment with pyrazole. Although cyclic AMP levels in the cerebral cortex change reciprocally after acute ethanol administration and during withdrawal, the increase observed during withdrawal is probably secondary to some withdrawal processes. Ethanol decreases cerebellar GABA levels only in rats which are stressed prior to sacrifice. Chronic intraventricular infusion of calcium increased the intensity of an acoustic startle response during ethanol withdrawal while EGTA infusion delayed the development of tolerance to the hypothermic effect of ethanol. The ratio of cyclic GMP to GABA levels is postulated to be important for expression of the withdrawal syndrome."}
{"id": "PMID:230954", "title": "Fructose-1,6-diphosphatase and glucose-6-phosphatase in newborn rats with intrauterine growth retardation.", "content": "The activities of two gluconeogenic enzymes, glucose-6-phosphatase and fructose-1,6-diphosphatase were examined in the normal and intrauterine growth retarded (IUGR) rat during the first 5 days of life. The fructose-1,6-diphosphatase activity, 1.54 +/- 0.10 mumol/min/g liver (means +/- SEM) in control and 1.47 +/- 0.20 in the IUGR rats, increased in both groups on days 2--4 but remained significantly lower in the IUGR rats through day 4 (4.53 +/- 0.6 mumol/min/g liver in control and 3.09 +/- 0.22 mumul/min/g liver in the IUGR rats, P less than 0.01). The glucose-6-phosphatase activity increased similarly in both groups. The weight of the IUGR rats remained lower through the third postnatal day (6.47 +/- 0.42 compared to 8.64 +/- 0.27 g in control rats). Blood glucose concentrations at birth were 117 +/- 11 mg/dl in control rats and 73 +/- 11 mg/dl in the IUGR rats (P less than 0.01). Although the glucose concentrations increased in both groups on days 2--4, the IUGR rats maintained relatively lower levels (P less than 0.01). The results indicate that IUGR fetal rats do not have augmented gluconeogenesis in spite of hypoglycemia. In addition, effective gluconeogenesis in the neonatal period appears to be delayed.", "contents": "Fructose-1,6-diphosphatase and glucose-6-phosphatase in newborn rats with intrauterine growth retardation. The activities of two gluconeogenic enzymes, glucose-6-phosphatase and fructose-1,6-diphosphatase were examined in the normal and intrauterine growth retarded (IUGR) rat during the first 5 days of life. The fructose-1,6-diphosphatase activity, 1.54 +/- 0.10 mumol/min/g liver (means +/- SEM) in control and 1.47 +/- 0.20 in the IUGR rats, increased in both groups on days 2--4 but remained significantly lower in the IUGR rats through day 4 (4.53 +/- 0.6 mumol/min/g liver in control and 3.09 +/- 0.22 mumul/min/g liver in the IUGR rats, P less than 0.01). The glucose-6-phosphatase activity increased similarly in both groups. The weight of the IUGR rats remained lower through the third postnatal day (6.47 +/- 0.42 compared to 8.64 +/- 0.27 g in control rats). Blood glucose concentrations at birth were 117 +/- 11 mg/dl in control rats and 73 +/- 11 mg/dl in the IUGR rats (P less than 0.01). Although the glucose concentrations increased in both groups on days 2--4, the IUGR rats maintained relatively lower levels (P less than 0.01). The results indicate that IUGR fetal rats do not have augmented gluconeogenesis in spite of hypoglycemia. In addition, effective gluconeogenesis in the neonatal period appears to be delayed."}
{"id": "PMID:230951", "title": "Effect of ethanol on cyclic nucleotides in vivo: consequences of controlling motor and respiratory changes.", "content": "Many psychotropic drugs alter cerebellar cyclic guanosine-3',5'-monophosphate (cGMP) content. Whereas apomorphine increased levels, central depressants such as ethanol, chlordiazepoxide or barbiturates, reduce the content of cerebellar cGMP without altering levels of cyclic adenosine-3',5'-monophosphate (cAMP). Additional data indicate that tolerance develops to this reduction of cerebellar cGMP by ethanol. In paralyzed animals, the increase in cerebellar cGMP content induced by apomorphine and the decrease caused by ethanol were dramatically attenuated. Since relatively high doses of ethanol were needed to decrease blood CO2 tension in spontaneously moving rats, changes in respiratory function appear to be  of only minor importance in the ethanol-induced decrease in cerebellar cGMP. It is concluded that ethanol-induced changes in content of cerebellar cGMP in vivo may be secondary to alterations in motor and, to a lesser extent, in respiratory function.", "contents": "Effect of ethanol on cyclic nucleotides in vivo: consequences of controlling motor and respiratory changes. Many psychotropic drugs alter cerebellar cyclic guanosine-3',5'-monophosphate (cGMP) content. Whereas apomorphine increased levels, central depressants such as ethanol, chlordiazepoxide or barbiturates, reduce the content of cerebellar cGMP without altering levels of cyclic adenosine-3',5'-monophosphate (cAMP). Additional data indicate that tolerance develops to this reduction of cerebellar cGMP by ethanol. In paralyzed animals, the increase in cerebellar cGMP content induced by apomorphine and the decrease caused by ethanol were dramatically attenuated. Since relatively high doses of ethanol were needed to decrease blood CO2 tension in spontaneously moving rats, changes in respiratory function appear to be  of only minor importance in the ethanol-induced decrease in cerebellar cGMP. It is concluded that ethanol-induced changes in content of cerebellar cGMP in vivo may be secondary to alterations in motor and, to a lesser extent, in respiratory function."}
{"id": "PMID:230950", "title": "Cyclic nucleotides in the development of alcohol tolerance and dependence: a commentary.", "content": "This paper aims to outline some of the caveats inherent in studies on first and second messengers in the central nervous system as related to tolerance and dependence. Analysis of systems based on measures of first and second messengers may be an over-simplification, since the actual molecular consequences of neurotransmission might result in a multilevel cascade of many sequential messages including protein kinase activation and protein phosphorylation and/or dephosphorylation.", "contents": "Cyclic nucleotides in the development of alcohol tolerance and dependence: a commentary. This paper aims to outline some of the caveats inherent in studies on first and second messengers in the central nervous system as related to tolerance and dependence. Analysis of systems based on measures of first and second messengers may be an over-simplification, since the actual molecular consequences of neurotransmission might result in a multilevel cascade of many sequential messages including protein kinase activation and protein phosphorylation and/or dephosphorylation."}
{"id": "PMID:230959", "title": "Effects of electric stress on glucose metabolism, glucose-stimulated cyclic adenosine 3',5'-monophosphate accumulation and 45 Ca++ efflux in isolated pancreatic islets from rats fed with a high fat diet.", "content": "The effects of the electric stress on glucose oxidation, cyclic adenosine 3', 5'-monophosphate (AMP) accumulation and 45Ca++ efflux in response to glucose were studied in pancreatic islets isolated from rats fed on a control (C) or a high fat diet (F) for 12 weeks. The half of rats on each diet were subjected to electrical shocks in the random time schedule for 1 hr per day for the last 3 weeks of the feeding period (group C-S and F-S). The remaining rats were not given any shocks (group C-NS and F-NS). The rats in F-S group had the high levels of plasma epinephrine, dopamine and blood glucose. The basal content of cyclic AMP after 20 min of incubation with 2.8 mM glucose was decreased in islets from F-S group without affecting insulin release. After 20 min of incubation with 25 mM glucose, the cyclic AMP content in islets from F-S group, which was identical with that in F-NS group, was only 50% of that in C-S group. Insulin release in response to high glucose was significantly inhibited in islets from F-S group. In spite of a remarkable increase of cyclic AMP content in islets from C-S group, insulin release did not differ from that in C-NS group. Glucose (16.7 mM)-stimulated 45Ca++ efflux from the perfused islets was greatly inhibited by the high fat diet rather than by stress. The rate of glucose oxidation with 16.7 mM glucose was decreased in islets from F-S group. It is suggested that the decreased insulin release in response to glucose provoked by the combined effects of the feeding of a high fat diet and electric stress may be mediated by changes of the adenylate cyclase-cyclic AMP system on the plasma membrane of the B-cell or be related to changes in glucose metabolism in islets.", "contents": "Effects of electric stress on glucose metabolism, glucose-stimulated cyclic adenosine 3',5'-monophosphate accumulation and 45 Ca++ efflux in isolated pancreatic islets from rats fed with a high fat diet. The effects of the electric stress on glucose oxidation, cyclic adenosine 3', 5'-monophosphate (AMP) accumulation and 45Ca++ efflux in response to glucose were studied in pancreatic islets isolated from rats fed on a control (C) or a high fat diet (F) for 12 weeks. The half of rats on each diet were subjected to electrical shocks in the random time schedule for 1 hr per day for the last 3 weeks of the feeding period (group C-S and F-S). The remaining rats were not given any shocks (group C-NS and F-NS). The rats in F-S group had the high levels of plasma epinephrine, dopamine and blood glucose. The basal content of cyclic AMP after 20 min of incubation with 2.8 mM glucose was decreased in islets from F-S group without affecting insulin release. After 20 min of incubation with 25 mM glucose, the cyclic AMP content in islets from F-S group, which was identical with that in F-NS group, was only 50% of that in C-S group. Insulin release in response to high glucose was significantly inhibited in islets from F-S group. In spite of a remarkable increase of cyclic AMP content in islets from C-S group, insulin release did not differ from that in C-NS group. Glucose (16.7 mM)-stimulated 45Ca++ efflux from the perfused islets was greatly inhibited by the high fat diet rather than by stress. The rate of glucose oxidation with 16.7 mM glucose was decreased in islets from F-S group. It is suggested that the decreased insulin release in response to glucose provoked by the combined effects of the feeding of a high fat diet and electric stress may be mediated by changes of the adenylate cyclase-cyclic AMP system on the plasma membrane of the B-cell or be related to changes in glucose metabolism in islets."}
{"id": "PMID:230960", "title": "A case of the syndrome of inappropriate secretion of TSH.", "content": "A girl aged 4 years with goiter and accelerated physical and skeletal growth was found to be hyperthyroid on the basis of elevated serum thyroid hormone level, nevertheless both the basal TSH and TSH responsiveness to TRH were maintained within the normal range. Serum TSH was suppressed by exogenous T3 and dexamethasone administration, but not significantly changed after propylthiouracil (PTU) treatment. The diurnal rhythmicity of anterior pituitary hormones was preserved with the high nocturnal peak of TSH and prolactin. Clinically, neither thyrotoxic signs nor evidences of pituitary tumor were observed. Her accelerated growth and elevated thyroid hormone level appeared to be induced by inappropriate secretion of TSH. In view of the literature, this is the first case of the syndrome of inappropriate secretion of TSH excluding the neoplastic origin in Japan.", "contents": "A case of the syndrome of inappropriate secretion of TSH. A girl aged 4 years with goiter and accelerated physical and skeletal growth was found to be hyperthyroid on the basis of elevated serum thyroid hormone level, nevertheless both the basal TSH and TSH responsiveness to TRH were maintained within the normal range. Serum TSH was suppressed by exogenous T3 and dexamethasone administration, but not significantly changed after propylthiouracil (PTU) treatment. The diurnal rhythmicity of anterior pituitary hormones was preserved with the high nocturnal peak of TSH and prolactin. Clinically, neither thyrotoxic signs nor evidences of pituitary tumor were observed. Her accelerated growth and elevated thyroid hormone level appeared to be induced by inappropriate secretion of TSH. In view of the literature, this is the first case of the syndrome of inappropriate secretion of TSH excluding the neoplastic origin in Japan."}
{"id": "PMID:230961", "title": "Lack of inhibition of ACTH-induced aldosterone stimulation by des-asp1-,ileu8-angiotensin II in man.", "content": "In 5 normal men an intravenous injection of 0.5 mg of synthetic 1-24 ACTH caused a significant increase in plasma aldosterone and a simultaneous intravenous infusion of 600 ng/kg/min of des-asp1-, ileu8-angiotensin II (AIIIA) did not inhibit this increase. Since this dose of AIIIA is known to inhibit an angiotensin II-induced increase in plasma aldosterone in normal men, the present results suggest that the ACTH-induced aldosterone stimulation is mediated by an adrenocortical receptor which is different from angiotensin II receptors.", "contents": "Lack of inhibition of ACTH-induced aldosterone stimulation by des-asp1-,ileu8-angiotensin II in man. In 5 normal men an intravenous injection of 0.5 mg of synthetic 1-24 ACTH caused a significant increase in plasma aldosterone and a simultaneous intravenous infusion of 600 ng/kg/min of des-asp1-, ileu8-angiotensin II (AIIIA) did not inhibit this increase. Since this dose of AIIIA is known to inhibit an angiotensin II-induced increase in plasma aldosterone in normal men, the present results suggest that the ACTH-induced aldosterone stimulation is mediated by an adrenocortical receptor which is different from angiotensin II receptors."}
{"id": "PMID:230962", "title": "Physical training under the influence of beta-blockade in rats. II. Effects on vascular reactivity.", "content": "Rats were treated by daily swimming or running exercises for 7 weeks. One group of rats was also trained under the influence of propranolol, while another group received daily propranolol injections only. The rat groups trained without beta blockade maintained a higher tail skin temperature when exposed to 5 degrees C after the 7-week training period. This phenomenon was not observable in the animals having received their training under the influence of beta-blockade. Both rat groups trained without beta-blockade showed increased vasodilatatory response to isoprenaline, as judged from a higher elevation of the tail skin temperature in response to the drug. This response was absent in the animal group having performed its training periods under the influence of propranolol. After the injection of phenylephrine the trained rats had a higher tail skin temperature than did the controls or propranolol-treated rats. The present results suggest an elevated sensitivity of beta 2-adrenoceptors and/or decreased sensitivity of alpha-adrenoceptors in trained rats. It is suggested that for the development of these changes repeated activation of the sympathetic nervous system by exercise periods is needed. That is why they are preventable if the training is performed under the influence of beta-blockade.", "contents": "Physical training under the influence of beta-blockade in rats. II. Effects on vascular reactivity. Rats were treated by daily swimming or running exercises for 7 weeks. One group of rats was also trained under the influence of propranolol, while another group received daily propranolol injections only. The rat groups trained without beta blockade maintained a higher tail skin temperature when exposed to 5 degrees C after the 7-week training period. This phenomenon was not observable in the animals having received their training under the influence of beta-blockade. Both rat groups trained without beta-blockade showed increased vasodilatatory response to isoprenaline, as judged from a higher elevation of the tail skin temperature in response to the drug. This response was absent in the animal group having performed its training periods under the influence of propranolol. After the injection of phenylephrine the trained rats had a higher tail skin temperature than did the controls or propranolol-treated rats. The present results suggest an elevated sensitivity of beta 2-adrenoceptors and/or decreased sensitivity of alpha-adrenoceptors in trained rats. It is suggested that for the development of these changes repeated activation of the sympathetic nervous system by exercise periods is needed. That is why they are preventable if the training is performed under the influence of beta-blockade."}
{"id": "PMID:230963", "title": "Purification and properties of a phosphorylase (phosphoprotein) phosphatase associated with an alkaline phosphatase of Mr 35000 from bovine adrenal cortex.", "content": "A metal-ion-independent, nonspecific phosphoprotein phosphatase (Mr = 35000) which represents the major phosphorylase phosphatase activity in bovine adrenal cortex has been purified to apparent homogeneity. An alkaline phosphatase activity (p-nitrophenyl phosphate as a substrate) of the same molecular weight, which requires both a metal ion (Mg2+ greater than Mn2+ greater than Co2+) and a sulfhydryl compound for activity, has been found to co-purify with the phosphoprotein phosphatase throughout the purification procedures. Characterization of the phosphoprotein and the alkaline phosphatase activities with respect to their catalytic properties, substrate and metal ion specificities, relationship with large molecular forms of the enzymes and responses to various effectors has been carried out. The results indicate that the phosphoprotein phosphatase can be converted by pyrophosphoryl compounds (e.g. PPi and ATP) to a metal-ion-dependent form which, subsequently, can be reactivated by Co2+ greater than Mn2+ but not by Mg2+ or Zn2+. The results also indicate that, although the phosphoprotein and the alkaline phosphatase activities are closely associated, they exhibit distinct physical and catalytic properties. Discussions concerning whether these two activities represent two different forms of the same protein or two different yet very similar polypeptide chains have been presented.", "contents": "Purification and properties of a phosphorylase (phosphoprotein) phosphatase associated with an alkaline phosphatase of Mr 35000 from bovine adrenal cortex. A metal-ion-independent, nonspecific phosphoprotein phosphatase (Mr = 35000) which represents the major phosphorylase phosphatase activity in bovine adrenal cortex has been purified to apparent homogeneity. An alkaline phosphatase activity (p-nitrophenyl phosphate as a substrate) of the same molecular weight, which requires both a metal ion (Mg2+ greater than Mn2+ greater than Co2+) and a sulfhydryl compound for activity, has been found to co-purify with the phosphoprotein phosphatase throughout the purification procedures. Characterization of the phosphoprotein and the alkaline phosphatase activities with respect to their catalytic properties, substrate and metal ion specificities, relationship with large molecular forms of the enzymes and responses to various effectors has been carried out. The results indicate that the phosphoprotein phosphatase can be converted by pyrophosphoryl compounds (e.g. PPi and ATP) to a metal-ion-dependent form which, subsequently, can be reactivated by Co2+ greater than Mn2+ but not by Mg2+ or Zn2+. The results also indicate that, although the phosphoprotein and the alkaline phosphatase activities are closely associated, they exhibit distinct physical and catalytic properties. Discussions concerning whether these two activities represent two different forms of the same protein or two different yet very similar polypeptide chains have been presented."}
{"id": "PMID:230964", "title": "Premature appearance of hepatic phosphoenolpyruvate carboxykinase in fetal rats, not mediated by adenosine 3':5'-monophosphate.", "content": "Injection of streptozotocin in utero to fetuses elicited a premature appearance of cytosolic hepatic activity of phosphoenol pyruvate carboxykinase. This was due to a precocious initiation of the synthesis of the enzyme. The streptozotocin-induced appearance of enzyme activity was not mediated by adenosine 3':5'-monophosphate since the concentration of the cyclic nucleotide in the liver was unaffected by the antibiotic, the administration of dibutyryladenosine 3':5'-monophosphate to streptozotocin-treated fetuses elicited an additive increase in enzyme activity, and insulin administration in utero repressed the streptozotocin effect while the effect due to dibutyryladenosine 3':5'-monophosphate was not inhibited by simultaneous insulin injection. Streptozotocin treatment also caused a small but consistent retardation of fetal growth and a marked reduction of liver wet weight. Histological analysis of the liver demonstrated a premature loss of some hematopoietic elements, while hepatocytes appeared normal. Hepatic protein synthesis was unaffected by the streptozotocin treatment. Streptozotocin treatment had no effect on fetal renal phosphoenol pyruvate carboxykinase activity or kidney wet weight.", "contents": "Premature appearance of hepatic phosphoenolpyruvate carboxykinase in fetal rats, not mediated by adenosine 3':5'-monophosphate. Injection of streptozotocin in utero to fetuses elicited a premature appearance of cytosolic hepatic activity of phosphoenol pyruvate carboxykinase. This was due to a precocious initiation of the synthesis of the enzyme. The streptozotocin-induced appearance of enzyme activity was not mediated by adenosine 3':5'-monophosphate since the concentration of the cyclic nucleotide in the liver was unaffected by the antibiotic, the administration of dibutyryladenosine 3':5'-monophosphate to streptozotocin-treated fetuses elicited an additive increase in enzyme activity, and insulin administration in utero repressed the streptozotocin effect while the effect due to dibutyryladenosine 3':5'-monophosphate was not inhibited by simultaneous insulin injection. Streptozotocin treatment also caused a small but consistent retardation of fetal growth and a marked reduction of liver wet weight. Histological analysis of the liver demonstrated a premature loss of some hematopoietic elements, while hepatocytes appeared normal. Hepatic protein synthesis was unaffected by the streptozotocin treatment. Streptozotocin treatment had no effect on fetal renal phosphoenol pyruvate carboxykinase activity or kidney wet weight."}
{"id": "PMID:230965", "title": "Mechanism of carbamoyl-phosphate synthetase. Properties of the two binding sites for ATP.", "content": "Carbamoyl phosphate synthethase I synthesizes carbamoyl phosphate from ammonia, HCO3- and two molecules of ATP, one of which, ATPA, yields Pi while the other, ATPB, yields the phosphoryl group of carbamoyl phosphate. Pulse-chase experiments with [gamma-32P]ATP without added HCO3- demonstrate separate binding sites for ATPA and ATPB. Bound ATPA dissociates readily from its site (t1/2 approximately 1--2 s) and the Kd is 0.2--0.7 mM. For the ATPB binding site the t1/2 for dissociation is 5--12 s and the Kd approximately 10 mM. Kd for ATPA seems to increase with enzyme concentration whereas Kd for ATPB does not change. HClO4 releases the ATP unchanged from the enzyme . ATPB and enzyme . ATPB . ATPA complexes. In the presence of HCO3-, ATP and N-acetylglutamate, an enzyme . ATPB . HCO3- . ATPA complex is formed. Its formation by the addition of HCO3- to the enzyme . ATPB . ATPA complex appears to involve an initial bimolecular addition reaction followed by an isomerization. Treatment with HClO4 releases Pi from ATPA but ATPB is released unchanged. Spontaneous hydrolysis of ATPA is responsible for the ATPase activity of the enzyme. Thus, a covalent bond may form between HCO3- and ATPA. However, ATPA can dissociate rapidly (t1/2 less than 10 s). The Kd for ATPA is approximately 0.2 mM. ATPB appears unable to dissociate from the enzyme . ATPB . HCO3- . ATPA complex since the t1/2 for dissociation of ATPB from the enzyme is lengthened about five times in the presence of 19 mM HCO3- and at 1 mM ATP. ATPA may also hydrolyse in this complex and be replaced by another molecule of ATP in the absence of exchange of ATPB. However, the ATPA binding site must be occupied to prevent ATPB release. ATPB may be bound in a pocket which becomes inaccessible to the solution when HCO3- and ATPA also bind. In contrast, HCO3- does not inhibit the binding of ATPB to the enzyme. Various intermediate steps in the formation of the enzyme . ATPb . HCO3- . ATPA complex are discussed. Additional evidence is presented that the ATPB binding site is only periodically accessible to ATP in solution and that ATPB in the steady-state reaction binds when the products leave. Since greater than 1.3 mol ATPB and greater than 1.8 mol ATPA bind/mol enzyme dimer, the enzyme monomer may be an active species.", "contents": "Mechanism of carbamoyl-phosphate synthetase. Properties of the two binding sites for ATP. Carbamoyl phosphate synthethase I synthesizes carbamoyl phosphate from ammonia, HCO3- and two molecules of ATP, one of which, ATPA, yields Pi while the other, ATPB, yields the phosphoryl group of carbamoyl phosphate. Pulse-chase experiments with [gamma-32P]ATP without added HCO3- demonstrate separate binding sites for ATPA and ATPB. Bound ATPA dissociates readily from its site (t1/2 approximately 1--2 s) and the Kd is 0.2--0.7 mM. For the ATPB binding site the t1/2 for dissociation is 5--12 s and the Kd approximately 10 mM. Kd for ATPA seems to increase with enzyme concentration whereas Kd for ATPB does not change. HClO4 releases the ATP unchanged from the enzyme . ATPB and enzyme . ATPB . ATPA complexes. In the presence of HCO3-, ATP and N-acetylglutamate, an enzyme . ATPB . HCO3- . ATPA complex is formed. Its formation by the addition of HCO3- to the enzyme . ATPB . ATPA complex appears to involve an initial bimolecular addition reaction followed by an isomerization. Treatment with HClO4 releases Pi from ATPA but ATPB is released unchanged. Spontaneous hydrolysis of ATPA is responsible for the ATPase activity of the enzyme. Thus, a covalent bond may form between HCO3- and ATPA. However, ATPA can dissociate rapidly (t1/2 less than 10 s). The Kd for ATPA is approximately 0.2 mM. ATPB appears unable to dissociate from the enzyme . ATPB . HCO3- . ATPA complex since the t1/2 for dissociation of ATPB from the enzyme is lengthened about five times in the presence of 19 mM HCO3- and at 1 mM ATP. ATPA may also hydrolyse in this complex and be replaced by another molecule of ATP in the absence of exchange of ATPB. However, the ATPA binding site must be occupied to prevent ATPB release. ATPB may be bound in a pocket which becomes inaccessible to the solution when HCO3- and ATPA also bind. In contrast, HCO3- does not inhibit the binding of ATPB to the enzyme. Various intermediate steps in the formation of the enzyme . ATPb . HCO3- . ATPA complex are discussed. Additional evidence is presented that the ATPB binding site is only periodically accessible to ATP in solution and that ATPB in the steady-state reaction binds when the products leave. Since greater than 1.3 mol ATPB and greater than 1.8 mol ATPA bind/mol enzyme dimer, the enzyme monomer may be an active species."}
{"id": "PMID:230966", "title": "Aerobic lactate synthesis by cardiac muscle.", "content": "Cardiac lactate production under aerobic conditions is absolutely dependent upon the availability of extracellular pyruvate. In the steady state, aerobic lactate output is largely independent of cardiac work load, but increases slightly when octanoate is included in addition to pyruvate in the perfusion fluid. Transient episodes of supra-normal lactate production are seen after sudden increases in cardiac work output, and also after transitions from octanoate to pyruvate in the perfusion media. These pulses of lactate production are invariably associated with the slow activation of pyruvate dehydrogenase in response to a sudden change in cardiac metabolic state, and they are abolished by pre-perfusion with dichloracetate, which converts pyruvate dehydrogenase into the fully active form. A second, additional component of the lactate pulses is sensitive to pre-perfusion with the transaminase inhibitor aminooxyacetate. The size of the second component is markedly dependent upon the precise protocol adopted for the experiment, and these variations suggest that the second component is associated with a major redistribution of cardiac Krebs' cycle intermediates and amino acids following the initial exposure to pyruvate-containing media. Steadystate aerobic lactate production is insensitive to both dichloroacetate and aminooxyacetate, and is thought to result from a direct exchange of malate for oxaloacetate across the heart mitochondrial membranes.", "contents": "Aerobic lactate synthesis by cardiac muscle. Cardiac lactate production under aerobic conditions is absolutely dependent upon the availability of extracellular pyruvate. In the steady state, aerobic lactate output is largely independent of cardiac work load, but increases slightly when octanoate is included in addition to pyruvate in the perfusion fluid. Transient episodes of supra-normal lactate production are seen after sudden increases in cardiac work output, and also after transitions from octanoate to pyruvate in the perfusion media. These pulses of lactate production are invariably associated with the slow activation of pyruvate dehydrogenase in response to a sudden change in cardiac metabolic state, and they are abolished by pre-perfusion with dichloracetate, which converts pyruvate dehydrogenase into the fully active form. A second, additional component of the lactate pulses is sensitive to pre-perfusion with the transaminase inhibitor aminooxyacetate. The size of the second component is markedly dependent upon the precise protocol adopted for the experiment, and these variations suggest that the second component is associated with a major redistribution of cardiac Krebs' cycle intermediates and amino acids following the initial exposure to pyruvate-containing media. Steadystate aerobic lactate production is insensitive to both dichloroacetate and aminooxyacetate, and is thought to result from a direct exchange of malate for oxaloacetate across the heart mitochondrial membranes."}
{"id": "PMID:230967", "title": "Polygraphic study during whole night sleep in infantile spasms.", "content": "The whole night EEG were polygraphically recorded and analyzed in 9 patients with infantile spasms prior to ACTH therapy. The subjects were divided into two groups, favorable and unfavorable, depending upon the response to the ACTH therapy. (1) Among the unfavorable group, the deep sleep stage was not observed; while the light sleep stage tended to dominate. (2) REM sleep period was noted less among the unfavorable than among the favorable group. REM density also tended to be lower among the unfavorable group. (3) Of the 4 unfavorable cases, 2 did not manifest REM sleep at all. Of the remaining 2, 1 had a remarkably long REM interval period. Even among the favorable cases, REM sleep tended to be short and appear frequently. (4) The period of muscle atonia during NREM sleep was markedly prolonged in all cases. (5) Body movements of both types (gross and twitch) were less frequent comparing to those of normal younger children, more remarkably in unfavorable cases. From the above findings, a disorder of the pontine reticular formation would be suggested in cases of infantile spasms. Reduction of body movements at each sleep stage might indicate abnormalities of monoamine metabolism in the brain stem of patients with this condition.", "contents": "Polygraphic study during whole night sleep in infantile spasms. The whole night EEG were polygraphically recorded and analyzed in 9 patients with infantile spasms prior to ACTH therapy. The subjects were divided into two groups, favorable and unfavorable, depending upon the response to the ACTH therapy. (1) Among the unfavorable group, the deep sleep stage was not observed; while the light sleep stage tended to dominate. (2) REM sleep period was noted less among the unfavorable than among the favorable group. REM density also tended to be lower among the unfavorable group. (3) Of the 4 unfavorable cases, 2 did not manifest REM sleep at all. Of the remaining 2, 1 had a remarkably long REM interval period. Even among the favorable cases, REM sleep tended to be short and appear frequently. (4) The period of muscle atonia during NREM sleep was markedly prolonged in all cases. (5) Body movements of both types (gross and twitch) were less frequent comparing to those of normal younger children, more remarkably in unfavorable cases. From the above findings, a disorder of the pontine reticular formation would be suggested in cases of infantile spasms. Reduction of body movements at each sleep stage might indicate abnormalities of monoamine metabolism in the brain stem of patients with this condition."}
{"id": "PMID:230968", "title": "Computerized automated syndromic and topographical neurologic diagnosis of lesions of the cranial nerves.", "content": "A system is described which, by means of a digital computer, computes from a previously automatically recorded objective neurologic finding a syndromic and topographical conclusion. For the present the system is designed and checked for lesions of the cranial nerves, but its principle is appropriate for the whole syndromic and topographical neurologic diagnosis.", "contents": "Computerized automated syndromic and topographical neurologic diagnosis of lesions of the cranial nerves. A system is described which, by means of a digital computer, computes from a previously automatically recorded objective neurologic finding a syndromic and topographical conclusion. For the present the system is designed and checked for lesions of the cranial nerves, but its principle is appropriate for the whole syndromic and topographical neurologic diagnosis."}
{"id": "PMID:230969", "title": "Cyclic neucleotides in progressive muscular dystrophy.", "content": "The authors radioimmunoassayed cyclic nucleotide concentrations in plasma and biopsied muscles of muscular dystrophy and muscles of chicken embryo. c-AMP concentrations in plasma were significantly lowered in Duchenne-type muscular dystrophy and this lowered degree was correlated with the stage of progression. Plasma c-GMP levels were also depressed in Duchenne-type dystrophy. In biopsied muscles, c-AMP concentrations per milligram of non-collagen protein were within normal limits. Therefore, the decrease of plasma c-AMP concentrations might be an expression of total metabolic changes rather than a pathologic process of the muscle itself. As for the dystrophic chicken embryo, both c-AMP and GMP concentrations were decreasing in the pectoral muscles in parallel with the advancement of hatching stages.", "contents": "Cyclic neucleotides in progressive muscular dystrophy. The authors radioimmunoassayed cyclic nucleotide concentrations in plasma and biopsied muscles of muscular dystrophy and muscles of chicken embryo. c-AMP concentrations in plasma were significantly lowered in Duchenne-type muscular dystrophy and this lowered degree was correlated with the stage of progression. Plasma c-GMP levels were also depressed in Duchenne-type dystrophy. In biopsied muscles, c-AMP concentrations per milligram of non-collagen protein were within normal limits. Therefore, the decrease of plasma c-AMP concentrations might be an expression of total metabolic changes rather than a pathologic process of the muscle itself. As for the dystrophic chicken embryo, both c-AMP and GMP concentrations were decreasing in the pectoral muscles in parallel with the advancement of hatching stages."}
{"id": "PMID:230973", "title": "The action of neurotensin on single myenteric neurones.", "content": "The action of neurotensin was studied on single myenteric neurones within ganglia of the myenteric plexus isolated from the guinea-pig ileum. Drugs were applied by adding them to the perfusing Krebs solution. Extracellular recording with glass suction electrodes indicated that neurotensin (100 pM-300 nM) caused a dose-dependent excitation of about 50% of myenteric neurones; the remaining neurones were unaffected. This effect persisted in calcium-free solutions. Intracellular recording showed that a similar proportion of Type 1 myenteric neurones were depolarized by neurotensin: this was associated with an increase in membrane resistance. Type 2 cells were either depolarized or hyperpolarized by neurotensin. The depolarization persisted in calcium-free solutions. The hyperpolarization disappeared in calcium-free solutions, suggesting either that the potential change itself is calcium-dependent or that it was due to release by neurotensin of a hyperpolarizing substance.", "contents": "The action of neurotensin on single myenteric neurones. The action of neurotensin was studied on single myenteric neurones within ganglia of the myenteric plexus isolated from the guinea-pig ileum. Drugs were applied by adding them to the perfusing Krebs solution. Extracellular recording with glass suction electrodes indicated that neurotensin (100 pM-300 nM) caused a dose-dependent excitation of about 50% of myenteric neurones; the remaining neurones were unaffected. This effect persisted in calcium-free solutions. Intracellular recording showed that a similar proportion of Type 1 myenteric neurones were depolarized by neurotensin: this was associated with an increase in membrane resistance. Type 2 cells were either depolarized or hyperpolarized by neurotensin. The depolarization persisted in calcium-free solutions. The hyperpolarization disappeared in calcium-free solutions, suggesting either that the potential change itself is calcium-dependent or that it was due to release by neurotensin of a hyperpolarizing substance."}
{"id": "PMID:230974", "title": "Indirect intestinal stimulatory effects of heroin: direct action on opiate receptors.", "content": "The effects of bolus intra-arterial doses of heroin and other stimulant drugs were studied in vascularly perfused isolated segments of dog small intestine. Heroin caused dose-related increases in intraluminal pressure similar in appearance to those caused by morphine. Perfusion with Krebs bicarbonate solution containing naloxone selectively abolished intestinal responses to heroin. Perfusion with cinanserin, a 5-hydroxytryptamine (5-HT) antagonist, decreased intestinal responses to 5-HT and heroin without affecting responses to dimethylphenylpiperazinium (DMPP) or bethanechol (BeCh). Tetrodotoxin reduced responses to heroin, 5-HT and DMPP but not responses to BeCh. Atropine antagonized contractile responses to all 4 stimulatory agents. These data indicate that heroin interacts with a conventional opiate receptor in the intestine and that the intestinal stimulatory effect of heroin is mediated by the release of endogenous 5-HT which activates intramural cholinergic neurons.", "contents": "Indirect intestinal stimulatory effects of heroin: direct action on opiate receptors. The effects of bolus intra-arterial doses of heroin and other stimulant drugs were studied in vascularly perfused isolated segments of dog small intestine. Heroin caused dose-related increases in intraluminal pressure similar in appearance to those caused by morphine. Perfusion with Krebs bicarbonate solution containing naloxone selectively abolished intestinal responses to heroin. Perfusion with cinanserin, a 5-hydroxytryptamine (5-HT) antagonist, decreased intestinal responses to 5-HT and heroin without affecting responses to dimethylphenylpiperazinium (DMPP) or bethanechol (BeCh). Tetrodotoxin reduced responses to heroin, 5-HT and DMPP but not responses to BeCh. Atropine antagonized contractile responses to all 4 stimulatory agents. These data indicate that heroin interacts with a conventional opiate receptor in the intestine and that the intestinal stimulatory effect of heroin is mediated by the release of endogenous 5-HT which activates intramural cholinergic neurons."}
{"id": "PMID:230975", "title": "Pretreatment with delta 1-tetrahydrocannabinol and psychoactive drugs: effects on uptake of biogenic amines and on behavior.", "content": "Injection of delta 1-tetrahydrocannabinol (THC) into mice increased the uptake into brain synaptosomes of radioactive DA, NE, 5-HT and GABA, with the effect on GABA being the greatest; uptake of leucine was not stimulated, indicating that THC does not facilitate the transport of amino acids in general. The effect of THC was stereospecific because pretreatment with the non-psychoactive isomer, (+) delta 6-THC had no effect on uptake of DA into cortical synaptosomes. The effect on DA uptake was correlated with psychoactive potency. THC enhanced uptake more than did SP-111 (a water soluble ester of THC but less potent than THC) and much more than cannabidiol (a non-psychoactive ingredient of marijuana). THC increased the uptake of DA into striatal synaptosomes but much less than into cortical synaptosomes. The enhancing effect of THC on uptake in cortex showed tolerance after chronic (1 week) treatment with THC. Catecholaminergic receptor antagonists (chlorpromazine, propranolol), like THC, stimulated the uptake of DA or NE into cortical synaptosomer. In contrast, pretreatment with MAO (pargyline) or uptake (tricyclic antidepressants) inhibitors, or with amphetamine, decreased uptake. Thus THC does not inhibit MAO uptake, or stimulate the release of catecholamines but may interact with a receptor. The notion of a THC--receptor interaction is supported by behavioral experiments.", "contents": "Pretreatment with delta 1-tetrahydrocannabinol and psychoactive drugs: effects on uptake of biogenic amines and on behavior. Injection of delta 1-tetrahydrocannabinol (THC) into mice increased the uptake into brain synaptosomes of radioactive DA, NE, 5-HT and GABA, with the effect on GABA being the greatest; uptake of leucine was not stimulated, indicating that THC does not facilitate the transport of amino acids in general. The effect of THC was stereospecific because pretreatment with the non-psychoactive isomer, (+) delta 6-THC had no effect on uptake of DA into cortical synaptosomes. The effect on DA uptake was correlated with psychoactive potency. THC enhanced uptake more than did SP-111 (a water soluble ester of THC but less potent than THC) and much more than cannabidiol (a non-psychoactive ingredient of marijuana). THC increased the uptake of DA into striatal synaptosomes but much less than into cortical synaptosomes. The enhancing effect of THC on uptake in cortex showed tolerance after chronic (1 week) treatment with THC. Catecholaminergic receptor antagonists (chlorpromazine, propranolol), like THC, stimulated the uptake of DA or NE into cortical synaptosomer. In contrast, pretreatment with MAO (pargyline) or uptake (tricyclic antidepressants) inhibitors, or with amphetamine, decreased uptake. Thus THC does not inhibit MAO uptake, or stimulate the release of catecholamines but may interact with a receptor. The notion of a THC--receptor interaction is supported by behavioral experiments."}
{"id": "PMID:230977", "title": "The role of calcium and cyclic AMP in the contractile action of angiotensin II upon rat descending colon.", "content": "The effect of procedures which affect calcium availability and tissue levels of cyclic AMP were investigated upon the contractions of rat colon to angiotensin II, PGE2 and KCl. Calcium free Tyrode containing EDTA (25 microM) reduced the response to angiotensin more than to PGE2 and KCl. An increase in calcium concentration to 3.6 mM potentiated responses to angiotensin and KCl. A further increase to either 7.2 mM or 10.8 mM still potentiated responses to angiotensin but those to KCl wre reduced. SKF 525A (2.6 x 10(-5) M) and verapamil (3.5 x 10(-6) M) inhibited the responses to KCl but the responses to PGE2 and angiotensin were less affected. Isoprenaline, Theophylline and dibutyryl cyclic AMP preferentially reduced the responses to angiotensin and PGE2. It is suggested that part of the response to angiotensin involves an influx of calcium, independent of depolarisation.", "contents": "The role of calcium and cyclic AMP in the contractile action of angiotensin II upon rat descending colon. The effect of procedures which affect calcium availability and tissue levels of cyclic AMP were investigated upon the contractions of rat colon to angiotensin II, PGE2 and KCl. Calcium free Tyrode containing EDTA (25 microM) reduced the response to angiotensin more than to PGE2 and KCl. An increase in calcium concentration to 3.6 mM potentiated responses to angiotensin and KCl. A further increase to either 7.2 mM or 10.8 mM still potentiated responses to angiotensin but those to KCl wre reduced. SKF 525A (2.6 x 10(-5) M) and verapamil (3.5 x 10(-6) M) inhibited the responses to KCl but the responses to PGE2 and angiotensin were less affected. Isoprenaline, Theophylline and dibutyryl cyclic AMP preferentially reduced the responses to angiotensin and PGE2. It is suggested that part of the response to angiotensin involves an influx of calcium, independent of depolarisation."}
{"id": "PMID:230978", "title": "Urotensin I effects on intracellular content of cyclic AMP in the rat tail artery.", "content": "Rat tail artery strips were incubated in the presence of 4 x 10(-3) M theophylline and urotensin I (UI). At the concentrations of 1.50, 7.50 mU/ml but not of 0.75 mU/ml UI, the content of cAMP increased significantly. Cyclic AMP content and muscle tension were measured at 5--30 sec intervals during noradrenaline (NA)- and potassium chloride (KCl)-induced contractions and during subsequent urotensin I-induced relaxation. Cyclic AMP content declined initially after addition of NA but returned to baseline levels during the contraction. Significant dose-related increases in cAMP were noted upon addition of UI, prior to the onset of the relaxation response followed by a marked decrease during the relaxation response. An increase in cAMP was observed after initiation of the contractile response to KCl-contracted tissues, but no further increase in cAMP after addition of UI was detected. These findings suggest an involvement of cyclic AMP in the initial events leading to the relaxation response to urotensin I in the NA-contracted rat tail artery. Urotensin I-induced relaxation in KCl-contracted tissues appears to proceed by an alternative mechanism which does not require increased levels of cAMP.", "contents": "Urotensin I effects on intracellular content of cyclic AMP in the rat tail artery. Rat tail artery strips were incubated in the presence of 4 x 10(-3) M theophylline and urotensin I (UI). At the concentrations of 1.50, 7.50 mU/ml but not of 0.75 mU/ml UI, the content of cAMP increased significantly. Cyclic AMP content and muscle tension were measured at 5--30 sec intervals during noradrenaline (NA)- and potassium chloride (KCl)-induced contractions and during subsequent urotensin I-induced relaxation. Cyclic AMP content declined initially after addition of NA but returned to baseline levels during the contraction. Significant dose-related increases in cAMP were noted upon addition of UI, prior to the onset of the relaxation response followed by a marked decrease during the relaxation response. An increase in cAMP was observed after initiation of the contractile response to KCl-contracted tissues, but no further increase in cAMP after addition of UI was detected. These findings suggest an involvement of cyclic AMP in the initial events leading to the relaxation response to urotensin I in the NA-contracted rat tail artery. Urotensin I-induced relaxation in KCl-contracted tissues appears to proceed by an alternative mechanism which does not require increased levels of cAMP."}
{"id": "PMID:230979", "title": "Norepinephrine stimulated cyclic AMP accumulation in rat limbic forebrain slices: partial mediation by a subpopulation of receptors with neither alpha nor beta characteristics.", "content": "Both isoproterenol and norepinephrine (NE) increase cyclic AMP in slices of the rat limbic forebrain and the responses are enhanced in the presence of the phosphodiesterase inhibitor RO 20-1724. However, even in the presence of RO 20-1724, no accumulation of cyclic AMP was observed after the addition of dopamine, serotonin or the alpha-agonists methoxamine and phenylephrine. This suggests that these agents do not activate adenylate cyclase in this preparation or that their respective receptors--unlike the beta-receptor--are not coupled to adenylate cyclase. Isoproterenol, which has a high affinity for this adenylate cyclase system but only 20-30% of the maximal activity of NE, does not interfere with the agonist activity of NE. Moreover, the effect of isoproterenol is not additive with that of NE thus suggesting that isoproterenol is acting on a subpopulation of NE receptors. The results indicate that two populations of NE receptors coupled to adenylate cyclase are present in slices of rat limbic forebrain: one which has beta-characteristics and the other with neither alpha- nor beta-characteristics based on agonist studies.", "contents": "Norepinephrine stimulated cyclic AMP accumulation in rat limbic forebrain slices: partial mediation by a subpopulation of receptors with neither alpha nor beta characteristics. Both isoproterenol and norepinephrine (NE) increase cyclic AMP in slices of the rat limbic forebrain and the responses are enhanced in the presence of the phosphodiesterase inhibitor RO 20-1724. However, even in the presence of RO 20-1724, no accumulation of cyclic AMP was observed after the addition of dopamine, serotonin or the alpha-agonists methoxamine and phenylephrine. This suggests that these agents do not activate adenylate cyclase in this preparation or that their respective receptors--unlike the beta-receptor--are not coupled to adenylate cyclase. Isoproterenol, which has a high affinity for this adenylate cyclase system but only 20-30% of the maximal activity of NE, does not interfere with the agonist activity of NE. Moreover, the effect of isoproterenol is not additive with that of NE thus suggesting that isoproterenol is acting on a subpopulation of NE receptors. The results indicate that two populations of NE receptors coupled to adenylate cyclase are present in slices of rat limbic forebrain: one which has beta-characteristics and the other with neither alpha- nor beta-characteristics based on agonist studies."}
{"id": "PMID:230980", "title": "Loss of beta-adrenoceptor binding sites in rat striatum following kainic acid lesions.", "content": "Intrastriatal injection of kainic acid (5 nmoles) to rats led to severe destruction of nerve cell bodies throughout the caudate-putamen complex and an extensive proliferation of glial cells. Lesioned striata displayed a significant 23% loss of beta-adrenoceptor binding sites 21--24 days after injection of kainic acid. Further analysis of these changes revealed that this loss of sites was selectively within the beta 1 receptor population. Although these results do not rule out a partial glial cell localisation for beta-adrenoceptors, they do indicate that at least a proportion of beta 1 receptors are present on striatal perikarya.", "contents": "Loss of beta-adrenoceptor binding sites in rat striatum following kainic acid lesions. Intrastriatal injection of kainic acid (5 nmoles) to rats led to severe destruction of nerve cell bodies throughout the caudate-putamen complex and an extensive proliferation of glial cells. Lesioned striata displayed a significant 23% loss of beta-adrenoceptor binding sites 21--24 days after injection of kainic acid. Further analysis of these changes revealed that this loss of sites was selectively within the beta 1 receptor population. Although these results do not rule out a partial glial cell localisation for beta-adrenoceptors, they do indicate that at least a proportion of beta 1 receptors are present on striatal perikarya."}
{"id": "PMID:230981", "title": "Inhibition by digoxin and SC4453 of (Na+ + K+)-ATPase prepared from human heart, guinea-pig heart and guinea-pig brain.", "content": "SC4453 is a digoxin analogue with a pyridazine instead of a lactone ring on C17 beta. SC4453 was compared with digoxin with respect to inhibition of (Na+ + K+)-ATPase prepared from human heart, guinea-pig heart and guinea-pig brain. SC4453 was slightly less potent than digoxin but showed a similar sensitivity to K+. As for cardenolides, species differences in sensitivity to SC4453 were accounted for by differences in the rate of dissociation from the receptors. These observations confirm that the human heart is one of the tissues most sensitive to cardiac glycosides.", "contents": "Inhibition by digoxin and SC4453 of (Na+ + K+)-ATPase prepared from human heart, guinea-pig heart and guinea-pig brain. SC4453 is a digoxin analogue with a pyridazine instead of a lactone ring on C17 beta. SC4453 was compared with digoxin with respect to inhibition of (Na+ + K+)-ATPase prepared from human heart, guinea-pig heart and guinea-pig brain. SC4453 was slightly less potent than digoxin but showed a similar sensitivity to K+. As for cardenolides, species differences in sensitivity to SC4453 were accounted for by differences in the rate of dissociation from the receptors. These observations confirm that the human heart is one of the tissues most sensitive to cardiac glycosides."}
{"id": "PMID:230982", "title": "Effect of naloxone, haloperidol and propranolol on cyclic 3',5'-adenosine monophosphate content of rat amygdala.", "content": "Naloxone (0.4 mg/kg, i.p.) causes an increase of cyclic adenosine monophosphate levels in the amygdala, but not in the hippocampus, caudate, or hypothalamus, of rats. The effect is antagonized by haloperidol (0.5 mg/kg, i.p.) and by propranolol (0.5 mg/kg, i.p.). This is consistent with the hypothesis of a tonic inhibitory influence of endogenous opiates on central dopaminergic and beta-noradrenergic systems. Haloperidol had an effect of its own on amygdala cyclic adenosine monophosphate levels which was blocked by propranolol. This suggests the possibility of an antagonistic interaction between dopaminergic and beta-noradrenergic innervation on this structure.", "contents": "Effect of naloxone, haloperidol and propranolol on cyclic 3',5'-adenosine monophosphate content of rat amygdala. Naloxone (0.4 mg/kg, i.p.) causes an increase of cyclic adenosine monophosphate levels in the amygdala, but not in the hippocampus, caudate, or hypothalamus, of rats. The effect is antagonized by haloperidol (0.5 mg/kg, i.p.) and by propranolol (0.5 mg/kg, i.p.). This is consistent with the hypothesis of a tonic inhibitory influence of endogenous opiates on central dopaminergic and beta-noradrenergic systems. Haloperidol had an effect of its own on amygdala cyclic adenosine monophosphate levels which was blocked by propranolol. This suggests the possibility of an antagonistic interaction between dopaminergic and beta-noradrenergic innervation on this structure."}
{"id": "PMID:230983", "title": "Inhibition of cardiac sympathetic neurotransmission by adenosine.", "content": "Experiments were performed to study the effect of adenosine on sympathetic neurotransmission to the myocardium. Adenosine administration to pentobarbital-anesthetized dogs resulted in decrease in blood pressure and significant impairment of cardioacceleration produced by stimulation of cardiac sympathetic nerves. The positive chronotropic effect of intravenous norepinephrine was not affected by adenosine. The blood pressure lowering as well as the inhibitory effect of adenosine on cardiac sympathetic nerve function could be significantly antagonized by theophylline. These results provide in vivo evidence in support of the hypothesis that adenosine caused inhibition of sympathetic neurotransmission via an action on purinergic receptors located on sympathetic nerve terminals.", "contents": "Inhibition of cardiac sympathetic neurotransmission by adenosine. Experiments were performed to study the effect of adenosine on sympathetic neurotransmission to the myocardium. Adenosine administration to pentobarbital-anesthetized dogs resulted in decrease in blood pressure and significant impairment of cardioacceleration produced by stimulation of cardiac sympathetic nerves. The positive chronotropic effect of intravenous norepinephrine was not affected by adenosine. The blood pressure lowering as well as the inhibitory effect of adenosine on cardiac sympathetic nerve function could be significantly antagonized by theophylline. These results provide in vivo evidence in support of the hypothesis that adenosine caused inhibition of sympathetic neurotransmission via an action on purinergic receptors located on sympathetic nerve terminals."}
{"id": "PMID:230984", "title": "Sanguinarine: a positive inotropic alkaloid which inhibits cardiac Na+,K+-ATPase.", "content": "In isolated, isometrically contracting left guinea pig atria, sanguinarine, a benzophenanthridine alkaloid from the papaveracea Sanguinaria canadensis, produced a concentration-dependent positive inotropic effect. Between 2.3 x 10(-6) M and 6.5 x 10(-5) M, sanguinarine increased contractility by 108% which was comparable to the maximal inotropic effect of ouabain. Within the same concentration range, sanguinarine caused inhibition of Na+,K+-ATPase isolated from guinea pig myocardium. 100% inhibition of Na+,K+,ATPase activity occurred at 1 x 10(-4) M sanguinarine. The I50 for enzyme inhibition and the ED50 for the inotropic action of sanguinarine were the same (6-6.5 x 10(-6) M) indicating that both effects may be causally related.", "contents": "Sanguinarine: a positive inotropic alkaloid which inhibits cardiac Na+,K+-ATPase. In isolated, isometrically contracting left guinea pig atria, sanguinarine, a benzophenanthridine alkaloid from the papaveracea Sanguinaria canadensis, produced a concentration-dependent positive inotropic effect. Between 2.3 x 10(-6) M and 6.5 x 10(-5) M, sanguinarine increased contractility by 108% which was comparable to the maximal inotropic effect of ouabain. Within the same concentration range, sanguinarine caused inhibition of Na+,K+-ATPase isolated from guinea pig myocardium. 100% inhibition of Na+,K+,ATPase activity occurred at 1 x 10(-4) M sanguinarine. The I50 for enzyme inhibition and the ED50 for the inotropic action of sanguinarine were the same (6-6.5 x 10(-6) M) indicating that both effects may be causally related."}
{"id": "PMID:230986", "title": "Fatal herpesvirus tamarinus infection in cotton-topped marmosets (Saguinus oedipus).", "content": "Fatal herpesvirus tamarinus infection was observed in cotton-topped marmosets (Saguinus oedipus) imported from South America via the United States on August 26, 1976. In addition to the lesions hitherto reported in herpesvirus tamarinus infection, severe degenerative and necrotic changes of ganglion cells were recognized with intranuclear inclusion bodies in the plexus of the digestive tract and the sympathetic nerves and their ganglions in the abdominal cavity. Inflammatory or regressive changes were also noted in the central nervous system. A large number of basophilic or eosinophilic intranuclear inclusion bodies frequently recognized in multinucleated giant cells were observed in various organs and tissues, and they showed different shapes at the electron microscopic level. Morphological findings indicated that herpesvirus tamarinus infection seemed to be similar to herpes simplex virus infection in man. The findings of the susceptibility of a variety of cell cultures to the virus isolate serologically identified as herpesvirus tamarinus and physicochemical characteristics of the virus isolate were in general agreement with the findings of herpesvirus tamarinus already reported by previous workers.", "contents": "Fatal herpesvirus tamarinus infection in cotton-topped marmosets (Saguinus oedipus). Fatal herpesvirus tamarinus infection was observed in cotton-topped marmosets (Saguinus oedipus) imported from South America via the United States on August 26, 1976. In addition to the lesions hitherto reported in herpesvirus tamarinus infection, severe degenerative and necrotic changes of ganglion cells were recognized with intranuclear inclusion bodies in the plexus of the digestive tract and the sympathetic nerves and their ganglions in the abdominal cavity. Inflammatory or regressive changes were also noted in the central nervous system. A large number of basophilic or eosinophilic intranuclear inclusion bodies frequently recognized in multinucleated giant cells were observed in various organs and tissues, and they showed different shapes at the electron microscopic level. Morphological findings indicated that herpesvirus tamarinus infection seemed to be similar to herpes simplex virus infection in man. The findings of the susceptibility of a variety of cell cultures to the virus isolate serologically identified as herpesvirus tamarinus and physicochemical characteristics of the virus isolate were in general agreement with the findings of herpesvirus tamarinus already reported by previous workers."}
{"id": "PMID:230987", "title": "[Synthesis and pharmacological activity of 1,2,3-triazole derivatives of naphthalene, quinoline and pyridine].", "content": "The preparation of three series of 1,2,3-triazol derivatives, with a naphthalene, quinoline or pyridine ring in 1 position, is described. Preliminary pharmacological screening of some of these compounds showed no appreciable activity.", "contents": "[Synthesis and pharmacological activity of 1,2,3-triazole derivatives of naphthalene, quinoline and pyridine]. The preparation of three series of 1,2,3-triazol derivatives, with a naphthalene, quinoline or pyridine ring in 1 position, is described. Preliminary pharmacological screening of some of these compounds showed no appreciable activity."}
{"id": "PMID:230989", "title": "[Variations of B- and T-lymphocytes in the peripheral blood and variations of the stimulability of cyclic nucleotides in the T-lymphocytes of patients suffering from malignant melanoma (author's transl)].", "content": "The portion of B- and T-lymphocytes at the whole white blood count have been estimated in patients with malignant melanoma. An elevation of the B-lymphocytes and a decrease of the T-lymphocytes could be observed in comparison to controls. The CAMP and CGMP level in lymphocytes of patients suffering from melanoma shows a correlation to the degree of metastasing changes. The cyclic nucleotides by mealanoma patients are influenced differently than by normal persons, after addition of physiologic stimulators (isoproterenole, PGE, PGF, acetylcholine). The beta-adrenergic system shows a decreased stimulability and the cholinergic system an increased one depending upon the disease stage in comparison to controls.", "contents": "[Variations of B- and T-lymphocytes in the peripheral blood and variations of the stimulability of cyclic nucleotides in the T-lymphocytes of patients suffering from malignant melanoma (author's transl)]. The portion of B- and T-lymphocytes at the whole white blood count have been estimated in patients with malignant melanoma. An elevation of the B-lymphocytes and a decrease of the T-lymphocytes could be observed in comparison to controls. The CAMP and CGMP level in lymphocytes of patients suffering from melanoma shows a correlation to the degree of metastasing changes. The cyclic nucleotides by mealanoma patients are influenced differently than by normal persons, after addition of physiologic stimulators (isoproterenole, PGE, PGF, acetylcholine). The beta-adrenergic system shows a decreased stimulability and the cholinergic system an increased one depending upon the disease stage in comparison to controls."}
{"id": "PMID:230990", "title": "Tissue-specific expression of onco-fetal antigens during embryogenesis.", "content": "It has become evident from recent literature that especially in tumor virus systems, cell transformation leads to an arrest of differentiation or to a retrodifferentiation. This may be reflected by the expression of embryonic antigens and it is therefore particularly important to characterize such antigens according to their specificity as well as to their specificity during embryogenesis. We have demonstrated the expression of embryonic antigens which are cross-reactive in avian fibroblasts transformed either by Rous sarcoma virus or by methylcholanthrene. This paper is intended to demonstrate that these embryonic antigens are detected only at a certain period of embryogenesis and particularly in muscle cells. They are detected only occasionally or not at all in cells of other tissues such as brain, liver, lung, and the digestive organs. These antigens are absent from the target cells before transformation and are consequently induced by the transforming agent, either viral or chemical. Therefore, these results suggest that by transformation mechanism, cells become specifically reverted to an earlier stage of differentiation (retrodifferentiation).", "contents": "Tissue-specific expression of onco-fetal antigens during embryogenesis. It has become evident from recent literature that especially in tumor virus systems, cell transformation leads to an arrest of differentiation or to a retrodifferentiation. This may be reflected by the expression of embryonic antigens and it is therefore particularly important to characterize such antigens according to their specificity as well as to their specificity during embryogenesis. We have demonstrated the expression of embryonic antigens which are cross-reactive in avian fibroblasts transformed either by Rous sarcoma virus or by methylcholanthrene. This paper is intended to demonstrate that these embryonic antigens are detected only at a certain period of embryogenesis and particularly in muscle cells. They are detected only occasionally or not at all in cells of other tissues such as brain, liver, lung, and the digestive organs. These antigens are absent from the target cells before transformation and are consequently induced by the transforming agent, either viral or chemical. Therefore, these results suggest that by transformation mechanism, cells become specifically reverted to an earlier stage of differentiation (retrodifferentiation)."}
{"id": "PMID:230991", "title": "Increase in levels of cyclic AMP during avian limb chondrogenesis in vitro.", "content": "In the present study the level of cAMP was measured during in vitro chondrogenesis of wing mesenchyme of stage 24 chick embryos and was found to increase significantly from 6.3 pmol/mg protein at the end of the first day of culture to 9.7 pmol/mg protein on the second day, when chondrogenic expression is first detected by the appearance of an Alcian blue staining extracellular matrix. Nonchondrogenic cultures derived from wings of stage 19 embryos had a lower level of cAMP (4.4 +/- 0.07 pmol/mg protein). The level of cAMP in intact wings was 4.5 +/- 0.4 pmol/mg protein and did not change between stages 19 through 25. The correlatin between increased levels of cAMP and the onset of chondrogenesis is consistent with a role of cAMP in the expression of differentiated functions in chondrocytes, as well as in some other cell types.", "contents": "Increase in levels of cyclic AMP during avian limb chondrogenesis in vitro. In the present study the level of cAMP was measured during in vitro chondrogenesis of wing mesenchyme of stage 24 chick embryos and was found to increase significantly from 6.3 pmol/mg protein at the end of the first day of culture to 9.7 pmol/mg protein on the second day, when chondrogenic expression is first detected by the appearance of an Alcian blue staining extracellular matrix. Nonchondrogenic cultures derived from wings of stage 19 embryos had a lower level of cAMP (4.4 +/- 0.07 pmol/mg protein). The level of cAMP in intact wings was 4.5 +/- 0.4 pmol/mg protein and did not change between stages 19 through 25. The correlatin between increased levels of cAMP and the onset of chondrogenesis is consistent with a role of cAMP in the expression of differentiated functions in chondrocytes, as well as in some other cell types."}
{"id": "PMID:230992", "title": "True divergent differentiation in a cellular slime mold, Polysphondylium pallidum.", "content": "Three abstract models of divergent cell differentiation to multiple cell types are presented. These differ primarily in the proportion of developmental events common to the pathways leading to each cell type. Two experimental approaches are outlined to determine which type best describes divergent differentiation occurring in a particular organism. The first technique is to describe and compare changes in labeling of specific polypeptides which characterize development to the several cell types. The second is to observe the ability of mutants which are blocked in one pathway to develop along alternate pathways. These approaches are applied to the case of Polysphondylium pallidum, where amebae develop into stalk cells, spores, or microcysts. It is concluded that cell differentiation in P. pallidum is of the truly divergent type in which developing cells show identical sequences of events until a branch point, and thereafter very different sequences of events.", "contents": "True divergent differentiation in a cellular slime mold, Polysphondylium pallidum. Three abstract models of divergent cell differentiation to multiple cell types are presented. These differ primarily in the proportion of developmental events common to the pathways leading to each cell type. Two experimental approaches are outlined to determine which type best describes divergent differentiation occurring in a particular organism. The first technique is to describe and compare changes in labeling of specific polypeptides which characterize development to the several cell types. The second is to observe the ability of mutants which are blocked in one pathway to develop along alternate pathways. These approaches are applied to the case of Polysphondylium pallidum, where amebae develop into stalk cells, spores, or microcysts. It is concluded that cell differentiation in P. pallidum is of the truly divergent type in which developing cells show identical sequences of events until a branch point, and thereafter very different sequences of events."}
{"id": "PMID:230993", "title": "Plasma lecithin: cholesterol acyltransferase activity in liver disease.", "content": "The plasma lecithin: cholesterol acyltransferase was determined in patients with various liver diseases and the relationship between this enzyme activity and the other liver function tests were studied including long term observations. Lecithin: cholesterol acyltransferase activity in fulminant hepatitis and liver cirrhosis showed a significant decrease in comparison with normal volunteers. Although the enzyme activity of hepatoma showed significant decrease, they were ascribed to the influence of concomitant liver cirrhosis. The enzyme activity showed insignificant changes in the acute and chronic hepatitis and alcoholic liver disease. Lecithin: cholesterol acyltransferase activity was correlated with the concentration of cholesterolester rather than with the ratio of esters to cholesterol. In addition, it was well correlated with pseudocholine esterase and serum albumin. The lecithin: cholesterol acyltransferase activity in the cases during follow-up period varied in good parallel with cholesterol-esters concentration and pseudocholine esterase in the cases with acute hepatitis; with serum albumin in the cases with liver cirrhosis. Furthermore, it varied inversely with SGPT in the cases with acute hepatitis. In a case with hepatoma, lecithin: cholesterol acyltransferase activity decreased more sharply than the cholesterolesters concentration and serum albumin immediately before death.", "contents": "Plasma lecithin: cholesterol acyltransferase activity in liver disease. The plasma lecithin: cholesterol acyltransferase was determined in patients with various liver diseases and the relationship between this enzyme activity and the other liver function tests were studied including long term observations. Lecithin: cholesterol acyltransferase activity in fulminant hepatitis and liver cirrhosis showed a significant decrease in comparison with normal volunteers. Although the enzyme activity of hepatoma showed significant decrease, they were ascribed to the influence of concomitant liver cirrhosis. The enzyme activity showed insignificant changes in the acute and chronic hepatitis and alcoholic liver disease. Lecithin: cholesterol acyltransferase activity was correlated with the concentration of cholesterolester rather than with the ratio of esters to cholesterol. In addition, it was well correlated with pseudocholine esterase and serum albumin. The lecithin: cholesterol acyltransferase activity in the cases during follow-up period varied in good parallel with cholesterol-esters concentration and pseudocholine esterase in the cases with acute hepatitis; with serum albumin in the cases with liver cirrhosis. Furthermore, it varied inversely with SGPT in the cases with acute hepatitis. In a case with hepatoma, lecithin: cholesterol acyltransferase activity decreased more sharply than the cholesterolesters concentration and serum albumin immediately before death."}
{"id": "PMID:230994", "title": "Incidence and clinical significance of HBe antigen and antibody in HBsAg-positive various liver diseases.", "content": "The HBeAg was detected in 5 of 24 patients with acute type B hepatitis (20.8%), 33 of 95 with chronic hepatitis (34.7%), 6 of 33 with liver cirrhosis (18.2%), and 3 of 39 with hepatocellular carcinoma (7.7%). On the other hand, anti-HBe was found in 4.2% of acute hepatitis, 18.9% of chronic hepatitis, 9.1% of liver cirrhosis, and 12.8% of hepatocellular carcinoma. We found that an early detection of HBeAg in patients with acute hepatitis is of no prognostic value, but its persistence may provide the earliest evidence of potential chronicity. In chronic liver diseases, HBeAg-positive cases showed remarkable fluctuations of serum transaminase levels, severe histological changes and poor responses to treatment. Many of the HBeAg-positive patients lost their initial positivity of HBeAg within six months or one year and in some cases serocoverted to anti-HBe after acute exacerbation. Follow-up study more than several years revealed that the presence of anti-HBe reflect an inactive stage and a more favorable outcome, whereas persistence of HBeAg may provide an active and continuing hepatocellular damage. From these results, we believed that serial measurements of HBeAg/anti-HBe system are useful prognostic marker in patients with HBsAg-positive liver disease.", "contents": "Incidence and clinical significance of HBe antigen and antibody in HBsAg-positive various liver diseases. The HBeAg was detected in 5 of 24 patients with acute type B hepatitis (20.8%), 33 of 95 with chronic hepatitis (34.7%), 6 of 33 with liver cirrhosis (18.2%), and 3 of 39 with hepatocellular carcinoma (7.7%). On the other hand, anti-HBe was found in 4.2% of acute hepatitis, 18.9% of chronic hepatitis, 9.1% of liver cirrhosis, and 12.8% of hepatocellular carcinoma. We found that an early detection of HBeAg in patients with acute hepatitis is of no prognostic value, but its persistence may provide the earliest evidence of potential chronicity. In chronic liver diseases, HBeAg-positive cases showed remarkable fluctuations of serum transaminase levels, severe histological changes and poor responses to treatment. Many of the HBeAg-positive patients lost their initial positivity of HBeAg within six months or one year and in some cases serocoverted to anti-HBe after acute exacerbation. Follow-up study more than several years revealed that the presence of anti-HBe reflect an inactive stage and a more favorable outcome, whereas persistence of HBeAg may provide an active and continuing hepatocellular damage. From these results, we believed that serial measurements of HBeAg/anti-HBe system are useful prognostic marker in patients with HBsAg-positive liver disease."}
{"id": "PMID:230997", "title": "Isolation and purification of human large bowel mucosal lymphoid cells: effect of separation technique on functional characteristics.", "content": "Human large bowel lamina propria lymphoid cells have been isolated using both mechanical and enzymatic techniques. Their separation from other cell types after isolation was effected with greater efficiency by sedimentation on isokinetic gradients than by filtration through glass bead columns. After being purified, the capacity of the lamina propria lymphocytes to function in vitro as effector cells in antibody-dependent cellular cytotoxicity was determined. Mechanical distruption of the mucosa gave low yields of lymphoid cells, which lacked the capacity for cytotoxicity. Enzymatic digestion of mucosal tissue, by comparison, yielded large numbers of viable lymphoid cells which retained a significant level of cytotoxic activity. Investigation revealed that mechanical homogenisation stimulated the synthesis of prostaglandin E2, and inhibitor studies showed that this mediator was responsible for the lack of cytotoxic activity in mechanically-liberated lymphocytes.", "contents": "Isolation and purification of human large bowel mucosal lymphoid cells: effect of separation technique on functional characteristics. Human large bowel lamina propria lymphoid cells have been isolated using both mechanical and enzymatic techniques. Their separation from other cell types after isolation was effected with greater efficiency by sedimentation on isokinetic gradients than by filtration through glass bead columns. After being purified, the capacity of the lamina propria lymphocytes to function in vitro as effector cells in antibody-dependent cellular cytotoxicity was determined. Mechanical distruption of the mucosa gave low yields of lymphoid cells, which lacked the capacity for cytotoxicity. Enzymatic digestion of mucosal tissue, by comparison, yielded large numbers of viable lymphoid cells which retained a significant level of cytotoxic activity. Investigation revealed that mechanical homogenisation stimulated the synthesis of prostaglandin E2, and inhibitor studies showed that this mediator was responsible for the lack of cytotoxic activity in mechanically-liberated lymphocytes."}
{"id": "PMID:230998", "title": "[Epstein-Barr virus and human chromosomes: Close association of the resident viral genome and the expression of the virus-determined nuclear antigen (EBNA) with the presence of chromosome 14 in human/mouse hybrid cells (author's transl)].", "content": "Fourteen hybrid clones derived from the fused cultures of human lymphoblastoid FV5 cells and 5-bromodeoxyuridine-resistant mouse fibroblastic MCB2 cells grown in HAT selective medium were examined for the presence of Epstein-Barr virus (EBV) DNA, the expression of the virus-determined nuclear antigen (EBNA), and the presence of human chromosomes, in the course of serial passage in vitro. Among the hybrid clones tested, three were positive for EBV DNA and EBNA, whereas the remaining 11 clones were totally negative. The chromosome investigations showed that human chromosome 14 was consistently involved in all three EBV genome-positive and EBNA-positive hybrid clones, but not in any negative clones. In 10 subclones isolated from one of the three positive clones, all of which contained chromosome 14 alone as human chromosomes, a concordant segregation of EBNA, EBV DNA and No. 14 chromosome was evident. These findings suggest that the resident EBV genome is closely associated with chromosome 14 and the presence of this particular chromosome alone is sufficient for the maintenance and the expression of EBV genetic information in human lymphoblastoid cells.", "contents": "[Epstein-Barr virus and human chromosomes: Close association of the resident viral genome and the expression of the virus-determined nuclear antigen (EBNA) with the presence of chromosome 14 in human/mouse hybrid cells (author's transl)]. Fourteen hybrid clones derived from the fused cultures of human lymphoblastoid FV5 cells and 5-bromodeoxyuridine-resistant mouse fibroblastic MCB2 cells grown in HAT selective medium were examined for the presence of Epstein-Barr virus (EBV) DNA, the expression of the virus-determined nuclear antigen (EBNA), and the presence of human chromosomes, in the course of serial passage in vitro. Among the hybrid clones tested, three were positive for EBV DNA and EBNA, whereas the remaining 11 clones were totally negative. The chromosome investigations showed that human chromosome 14 was consistently involved in all three EBV genome-positive and EBNA-positive hybrid clones, but not in any negative clones. In 10 subclones isolated from one of the three positive clones, all of which contained chromosome 14 alone as human chromosomes, a concordant segregation of EBNA, EBV DNA and No. 14 chromosome was evident. These findings suggest that the resident EBV genome is closely associated with chromosome 14 and the presence of this particular chromosome alone is sufficient for the maintenance and the expression of EBV genetic information in human lymphoblastoid cells."}
{"id": "PMID:231000", "title": "[Study on glycolipids in human lung carcinoma of histologically different types (author's transl)].", "content": "Human lung carcinoma tissues with histological types of adenocarcinoma, squamous cell and small cell undifferentiated carcinomas were investigated for glycolipids. Carcinoma tissues, as well as normal adult and embryonic lungs contained ceramide mono-, di- and trihexosides, globoside and hematoside as major glycolipids. In addition to them, sulfatide which was identified as ceramide 3-sulfate-galactoside, was isolated in much lesser amount. The content of sulfatide was markedly increased in adenocarcinoma than that in other carcinomas and normal lung. Adenocarcinoma was also characterized by significantly lower level of total glycolipids which was largely due to the diminished contents of ceramide mono- and dihexosides, and hematoside, as compared to those in other two carcinomas. Squamous cell carcinoma had a characteristic pattern with an increment of hematoside. In small cell undifferentiated carcinoma, glycolipid contents were similar with those in squamous cell carcinoma but the relative composition of major glycolipids was markedly differed from that in other types. All the types of carcinoma examined showed marked increase of ceramide mono- and dihexosides (except for ceramide dihexoside in adenocarcinoma) compared to those in normal adult lung. Overall feature of glycolipids in embryonic lung appeared to be an intermediate between carcinomas and normal adult lung.", "contents": "[Study on glycolipids in human lung carcinoma of histologically different types (author's transl)]. Human lung carcinoma tissues with histological types of adenocarcinoma, squamous cell and small cell undifferentiated carcinomas were investigated for glycolipids. Carcinoma tissues, as well as normal adult and embryonic lungs contained ceramide mono-, di- and trihexosides, globoside and hematoside as major glycolipids. In addition to them, sulfatide which was identified as ceramide 3-sulfate-galactoside, was isolated in much lesser amount. The content of sulfatide was markedly increased in adenocarcinoma than that in other carcinomas and normal lung. Adenocarcinoma was also characterized by significantly lower level of total glycolipids which was largely due to the diminished contents of ceramide mono- and dihexosides, and hematoside, as compared to those in other two carcinomas. Squamous cell carcinoma had a characteristic pattern with an increment of hematoside. In small cell undifferentiated carcinoma, glycolipid contents were similar with those in squamous cell carcinoma but the relative composition of major glycolipids was markedly differed from that in other types. All the types of carcinoma examined showed marked increase of ceramide mono- and dihexosides (except for ceramide dihexoside in adenocarcinoma) compared to those in normal adult lung. Overall feature of glycolipids in embryonic lung appeared to be an intermediate between carcinomas and normal adult lung."}
{"id": "PMID:231001", "title": "[Clinical study on aldolase isoenzyme--the development of the method of cancer diagnosis with muscle type aldolase (author's transl)].", "content": "A specific radioimmunoassay was developed for the quantitation of human muscle type aldolase (M-ALD) in human serum. The amount of M-ALD antigen present in 135 sera from normal healthy subjects, noncancer patients and cancer patients was determined. The serum M-ALD value for the 41 normal healthy subjects averaged 171 +/- 39 ng/ml and they had a range from 130 ng/ml to 210 ng/ml. In 33 noncancer hospital patients, excluding patients with muscle diseases, the serum M-ALD values averaged 164 ng/ml and had a range of 125 to 220 ng/ml. In contrast the 61 cancer patients had serum M-ALD values which averaged 586 ng/ml and had a range of 85 to 5800 ng/ml. Eighty two percent of the cancer patients had serum concentrations of M-ALD which were outside of the normal range. The CEA value was determined in the serum of the cancer patients and thirty five percent of the patients had elevated serum concentrations. The measurement of M-ALD values in human serum may be an additional laboratory test in the diagnosis and follow up of the cancer patients.", "contents": "[Clinical study on aldolase isoenzyme--the development of the method of cancer diagnosis with muscle type aldolase (author's transl)]. A specific radioimmunoassay was developed for the quantitation of human muscle type aldolase (M-ALD) in human serum. The amount of M-ALD antigen present in 135 sera from normal healthy subjects, noncancer patients and cancer patients was determined. The serum M-ALD value for the 41 normal healthy subjects averaged 171 +/- 39 ng/ml and they had a range from 130 ng/ml to 210 ng/ml. In 33 noncancer hospital patients, excluding patients with muscle diseases, the serum M-ALD values averaged 164 ng/ml and had a range of 125 to 220 ng/ml. In contrast the 61 cancer patients had serum M-ALD values which averaged 586 ng/ml and had a range of 85 to 5800 ng/ml. Eighty two percent of the cancer patients had serum concentrations of M-ALD which were outside of the normal range. The CEA value was determined in the serum of the cancer patients and thirty five percent of the patients had elevated serum concentrations. The measurement of M-ALD values in human serum may be an additional laboratory test in the diagnosis and follow up of the cancer patients."}
{"id": "PMID:231002", "title": "[Experimental and clinical studies on blood coagulation and lysis system after hepatic resection (author's transl)].", "content": "Blood coagulation and lysis system was studied with other biochemical serum analysis in three groups of mongrel dogs; laparotomy without hepatic resection (group I), with 50% hepatic section (group II), and 70% hepatic resection (group III). In clinical studies, six cases of hepatic tumors and one case of hepatoma with cirrhosis were selected for examinations. All the data examined in group I were restored toward normal within 48 hours. Total serum protein level was significantly decreased after hepatic resection. The protein level in group III was lower than in group II on the 4th postoperative day (P less than 0.01). In clinical studies, low serum protein levels did not reach a preoperative value even 3 weeks after extended right hepatic lobectomy. Time course of Al-P and transaminase changes in clinical studies was similar to that in experimental study with dogs. Al-P and transaminase showed an abnormally high level in the patient with hepatic cirrhosis. Serum bilirubin levels were not increased after hepatic resection. In blood coagulation and lysis system, serum fibrinogen levels were markedly decreased: 50% reduction in group III and 30% reduction in group II on the first postoperative day. The degree of decrease in the fibrinogen level was proportional to the size of resected volume of the liver. On the other hand, in clinical studies fibrinogen levels were slightly decreased. In the case of hepatic resection with cirrhosis, however, the values were markedly decreased: 40% reduction on the 4th and 25% on the 21st postoperative days. Fibrinolysis system was accelerated group II and III. The acceleration continued until 3 weeks after hepatic resection. From these results it may be concluded that analysis of blood coagulation and lysis system after hepatic resection is useful in evaluating a residual hepatic function after partial resection and in selecting a treatment suitable for hepatic insufficiency.", "contents": "[Experimental and clinical studies on blood coagulation and lysis system after hepatic resection (author's transl)]. Blood coagulation and lysis system was studied with other biochemical serum analysis in three groups of mongrel dogs; laparotomy without hepatic resection (group I), with 50% hepatic section (group II), and 70% hepatic resection (group III). In clinical studies, six cases of hepatic tumors and one case of hepatoma with cirrhosis were selected for examinations. All the data examined in group I were restored toward normal within 48 hours. Total serum protein level was significantly decreased after hepatic resection. The protein level in group III was lower than in group II on the 4th postoperative day (P less than 0.01). In clinical studies, low serum protein levels did not reach a preoperative value even 3 weeks after extended right hepatic lobectomy. Time course of Al-P and transaminase changes in clinical studies was similar to that in experimental study with dogs. Al-P and transaminase showed an abnormally high level in the patient with hepatic cirrhosis. Serum bilirubin levels were not increased after hepatic resection. In blood coagulation and lysis system, serum fibrinogen levels were markedly decreased: 50% reduction in group III and 30% reduction in group II on the first postoperative day. The degree of decrease in the fibrinogen level was proportional to the size of resected volume of the liver. On the other hand, in clinical studies fibrinogen levels were slightly decreased. In the case of hepatic resection with cirrhosis, however, the values were markedly decreased: 40% reduction on the 4th and 25% on the 21st postoperative days. Fibrinolysis system was accelerated group II and III. The acceleration continued until 3 weeks after hepatic resection. From these results it may be concluded that analysis of blood coagulation and lysis system after hepatic resection is useful in evaluating a residual hepatic function after partial resection and in selecting a treatment suitable for hepatic insufficiency."}
{"id": "PMID:231003", "title": "Intrinsic ADP-ribose transferase activity versus levels of mono(adp-ribose)protein conjugates in proliferating Ehrlich ascites tumor cells.", "content": "Transition of proliferating Ehrlich ascites tumor cells (3 days after transplantation) to the non-proliferating status (8--14 days after transplantation) was associated with an increase in total mono (ADP-ribose) protein conjugates. This increase was largely confined to the NH2OH-resistant subfraction. When the amounts of mono-(ADP-ribose) conjugates from 20% trichloroacetic acid precipitates were compared with those from 5% perchloric acid precipitates, no significant differences were seen. This fact excludes histone H1 as a major mono (ADP-ribose) acceptor in vivo in these cells. Transition to the resting state was also associated with a small decrease in NAD levels, and with no significant changes of total ADP-ribose transferase activity. However intrinsic ADP-ribose transferase activity as expressed in permeabilized cells was increased, being correlated with the changes in the level of the NH2OH-resistant mono (ADP-ribose) protein conjugates. This shows that alterations in intrinsic transferase activity may, in general, indicate similar alterations in major subfractions of ADP-ribose conjugates. Intrinsic ADP-ribose transferase activity exhibited an inverse relationship to ornithine decarboxylase activity.", "contents": "Intrinsic ADP-ribose transferase activity versus levels of mono(adp-ribose)protein conjugates in proliferating Ehrlich ascites tumor cells. Transition of proliferating Ehrlich ascites tumor cells (3 days after transplantation) to the non-proliferating status (8--14 days after transplantation) was associated with an increase in total mono (ADP-ribose) protein conjugates. This increase was largely confined to the NH2OH-resistant subfraction. When the amounts of mono-(ADP-ribose) conjugates from 20% trichloroacetic acid precipitates were compared with those from 5% perchloric acid precipitates, no significant differences were seen. This fact excludes histone H1 as a major mono (ADP-ribose) acceptor in vivo in these cells. Transition to the resting state was also associated with a small decrease in NAD levels, and with no significant changes of total ADP-ribose transferase activity. However intrinsic ADP-ribose transferase activity as expressed in permeabilized cells was increased, being correlated with the changes in the level of the NH2OH-resistant mono (ADP-ribose) protein conjugates. This shows that alterations in intrinsic transferase activity may, in general, indicate similar alterations in major subfractions of ADP-ribose conjugates. Intrinsic ADP-ribose transferase activity exhibited an inverse relationship to ornithine decarboxylase activity."}
{"id": "PMID:231004", "title": "Cerebral microvessels and derived cells in tissue culture: isolation and preliminary characterization.", "content": "Microvessels isolated from mouse forebrain were used as the source material for the derivation of cerebral vascular endothelium and smooth-muscle cells in culture. The microvessels were isolated by a mechanical dispersion and filtration technique, and were maintained in vitro as organoid cultures. A microvessel classification system was developed and proved to be useful as a tool in monitoring culture progress and in predicting the type(s) of microvessel(s) that would give rise to migrating and/or proliferating cells. The isolated cerebral microvessels were heterogeneous in diameter, size of individual vascular isolate, and proliferative potential. The isolated microvessels ranged in diameter from 4 micron to 25 micron and in size from a single microvascular segment to a large multibranched plexus with mural cells. The initial viability, determined by erythrosin B exclusion, was approximately 50% on a per cell basis. All microvessel classes had proliferative potential although the rate and extent of proliferation were both microvessel class- and density-dependent. The smaller microvessels gave rise to endothelial cells, whereas the large microvessels gave rise to endothelial and smooth-muscle cells. The viability and progress of a microvessel toward derived cell proliferation seemed to be directly proportional to the number of mural cells present.", "contents": "Cerebral microvessels and derived cells in tissue culture: isolation and preliminary characterization. Microvessels isolated from mouse forebrain were used as the source material for the derivation of cerebral vascular endothelium and smooth-muscle cells in culture. The microvessels were isolated by a mechanical dispersion and filtration technique, and were maintained in vitro as organoid cultures. A microvessel classification system was developed and proved to be useful as a tool in monitoring culture progress and in predicting the type(s) of microvessel(s) that would give rise to migrating and/or proliferating cells. The isolated cerebral microvessels were heterogeneous in diameter, size of individual vascular isolate, and proliferative potential. The isolated microvessels ranged in diameter from 4 micron to 25 micron and in size from a single microvascular segment to a large multibranched plexus with mural cells. The initial viability, determined by erythrosin B exclusion, was approximately 50% on a per cell basis. All microvessel classes had proliferative potential although the rate and extent of proliferation were both microvessel class- and density-dependent. The smaller microvessels gave rise to endothelial cells, whereas the large microvessels gave rise to endothelial and smooth-muscle cells. The viability and progress of a microvessel toward derived cell proliferation seemed to be directly proportional to the number of mural cells present."}
{"id": "PMID:231005", "title": "Effects of culture conditions on the synthesis of human chorionic gonadotropin by placental organ cultures.", "content": "Culture conditions for maintaining first trimester human placenta in organ culture, which enhance the secretion of human chorionic gonadotropin (hCG), are described. Nutrient medium, oxygen tension and Gelfoam support matrix influence the synthesis of hCG by these cultures. Placental tissue remained viable for the duration of experiments (12 days) as judged by the incorporation of tritiated thymidine into DNA and the lack of release of incorporated [125I]iododeoxyuridine. Optimal conditions for hCG synthesis in placental organ culture included an atmosphere of 95% air and 5% Co2 (approximately 20% O2), CMRL 1066 medium containing fetal human or bovine serum, insulin, hydrocortisone and retinal acetate. Multiple pieces of placenta could be cultured in the same dish with an additive effect on hCG secretion. The functional responsiveness of these placental cultures was demonstrated by modulation of hCG synthesis with theophylline and 3'5' dibutyryl cyclic AMP.", "contents": "Effects of culture conditions on the synthesis of human chorionic gonadotropin by placental organ cultures. Culture conditions for maintaining first trimester human placenta in organ culture, which enhance the secretion of human chorionic gonadotropin (hCG), are described. Nutrient medium, oxygen tension and Gelfoam support matrix influence the synthesis of hCG by these cultures. Placental tissue remained viable for the duration of experiments (12 days) as judged by the incorporation of tritiated thymidine into DNA and the lack of release of incorporated [125I]iododeoxyuridine. Optimal conditions for hCG synthesis in placental organ culture included an atmosphere of 95% air and 5% Co2 (approximately 20% O2), CMRL 1066 medium containing fetal human or bovine serum, insulin, hydrocortisone and retinal acetate. Multiple pieces of placenta could be cultured in the same dish with an additive effect on hCG secretion. The functional responsiveness of these placental cultures was demonstrated by modulation of hCG synthesis with theophylline and 3'5' dibutyryl cyclic AMP."}
{"id": "PMID:231008", "title": "Biology of mouse thymic virus, a herpesvirus of mice, and the antigenic relationship to mouse cytomegalovirus.", "content": "Mouse thymic virus (TA) is a herpesvirus which produces extensive necrosis of the thymus of newborn mice 7 to 14 days after infection. Infectious virus can be recovered from the thymus for only 10 days after infection, with highest titers occurring between days 5 and 7. In mice 5 days old or less, TA infects thymus cells and produces massive necrosis. TA also infects the salivary glands and persists as a chronic infection. Newborn mice infected with TA have no detectable humoral immune response. Infected adult mice respond, and humoral antibody is detected 7 days after infection. Titers are maintained for months thereafter. Regardless of the age of the mice inoculated with TA, persistent infection was established in the salivary glands, but no evidence for thymus involvement was observed when adults were infected. TA does not cross-react serologically by immunofluorescent, complement fixation, or virus neutralization tests with mouse cytomegalovirus; however, interestingly, the epidemiology of the two herpesviruses are similar. Both mouse cytomegalovirus and TA were isolated from the same animals in populations of laboratory and wild mice. Evidence of infection with mouse cytomegalovirus and TA were most apparent by virus isolations, since humoral antibody responses are rarely observed. All strains of mice tested were susceptible to TA infection. However, in some strains maximum necrosis occurred at 7 days, compared with 10 to 14 days for other strains. The difference in age susceptibility and the target tissue of thymus in newborn mice suggests that TA is a model herpesvirus for studying the effects of viral infections on humoral and cell-mediated immunological functions.", "contents": "Biology of mouse thymic virus, a herpesvirus of mice, and the antigenic relationship to mouse cytomegalovirus. Mouse thymic virus (TA) is a herpesvirus which produces extensive necrosis of the thymus of newborn mice 7 to 14 days after infection. Infectious virus can be recovered from the thymus for only 10 days after infection, with highest titers occurring between days 5 and 7. In mice 5 days old or less, TA infects thymus cells and produces massive necrosis. TA also infects the salivary glands and persists as a chronic infection. Newborn mice infected with TA have no detectable humoral immune response. Infected adult mice respond, and humoral antibody is detected 7 days after infection. Titers are maintained for months thereafter. Regardless of the age of the mice inoculated with TA, persistent infection was established in the salivary glands, but no evidence for thymus involvement was observed when adults were infected. TA does not cross-react serologically by immunofluorescent, complement fixation, or virus neutralization tests with mouse cytomegalovirus; however, interestingly, the epidemiology of the two herpesviruses are similar. Both mouse cytomegalovirus and TA were isolated from the same animals in populations of laboratory and wild mice. Evidence of infection with mouse cytomegalovirus and TA were most apparent by virus isolations, since humoral antibody responses are rarely observed. All strains of mice tested were susceptible to TA infection. However, in some strains maximum necrosis occurred at 7 days, compared with 10 to 14 days for other strains. The difference in age susceptibility and the target tissue of thymus in newborn mice suggests that TA is a model herpesvirus for studying the effects of viral infections on humoral and cell-mediated immunological functions."}
{"id": "PMID:231009", "title": "Difference in capacity of Sendai virus envelope components to induce cytotoxic T lymphocytes in primary and secondary immune responses.", "content": "Studies were made on the abilities of Sendai virus envelope components to induce primary and secondary generations of virus-specific cytotoxic mouse T lymphocytes (CTL). The primary CTL response in BALB/c mice was induced by reassembled envelope particles that had fusion activity but not by envelope glycoproteins without fusion activity, although both preparations induced a humoral immune response. Reconstitution of membrane-bound envelope proteins from envelope glycoproteins with lipids restored the fusion activity and the capacity to induce CTL. Target cells susceptible to virus-specific CTL could be induced by reassembled envelope particles, but not by envelope glycoproteins or LLC-MK2 cell-grown Sendai virus, neither of which had fusion activity. On the other hand, all the viruses and envelope components tested were found to stimulate a virus-specific CTL response in the in vitro secondary generation of CTL from virus-primed spleen cells. These results suggest that Senaei virus fusion activity is involved in primary induction of the CTL response as well as in target cell formation, but that it is not essential for secondary stimulation of the CTL response.", "contents": "Difference in capacity of Sendai virus envelope components to induce cytotoxic T lymphocytes in primary and secondary immune responses. Studies were made on the abilities of Sendai virus envelope components to induce primary and secondary generations of virus-specific cytotoxic mouse T lymphocytes (CTL). The primary CTL response in BALB/c mice was induced by reassembled envelope particles that had fusion activity but not by envelope glycoproteins without fusion activity, although both preparations induced a humoral immune response. Reconstitution of membrane-bound envelope proteins from envelope glycoproteins with lipids restored the fusion activity and the capacity to induce CTL. Target cells susceptible to virus-specific CTL could be induced by reassembled envelope particles, but not by envelope glycoproteins or LLC-MK2 cell-grown Sendai virus, neither of which had fusion activity. On the other hand, all the viruses and envelope components tested were found to stimulate a virus-specific CTL response in the in vitro secondary generation of CTL from virus-primed spleen cells. These results suggest that Senaei virus fusion activity is involved in primary induction of the CTL response as well as in target cell formation, but that it is not essential for secondary stimulation of the CTL response."}
{"id": "PMID:231010", "title": "Interaction of murine cytomegalovirus with separated populations of spleen cells.", "content": "Mouse spleen cultures were infected with murine cytomegalovirus, either before or after separating the cells into various classes, and the growth of virus and production of infectious centers were measured in each cell class. The separation techniques, which were used in various combinations, comprised: adherence to plastic surfaces; adherence to nylon wool columns; gamma irradiation; and treatment with anti-immunoglobulin serum plus complement. The \"macrophage population\" took up most of the input virus, as shown by autoradiography of spleen cells infected with radioactive virus. These cells formed infectious centers but replicated the virus only transiently. In contrast, the \"B-lymphocyte population\" contained a minor cell fraction which was permissive for replication. The \"T-lymphocyte population\" appeared to be nonpermissive for replication and did not produce infectious centers.", "contents": "Interaction of murine cytomegalovirus with separated populations of spleen cells. Mouse spleen cultures were infected with murine cytomegalovirus, either before or after separating the cells into various classes, and the growth of virus and production of infectious centers were measured in each cell class. The separation techniques, which were used in various combinations, comprised: adherence to plastic surfaces; adherence to nylon wool columns; gamma irradiation; and treatment with anti-immunoglobulin serum plus complement. The \"macrophage population\" took up most of the input virus, as shown by autoradiography of spleen cells infected with radioactive virus. These cells formed infectious centers but replicated the virus only transiently. In contrast, the \"B-lymphocyte population\" contained a minor cell fraction which was permissive for replication. The \"T-lymphocyte population\" appeared to be nonpermissive for replication and did not produce infectious centers."}
{"id": "PMID:231007", "title": "Effect of intracisternal injection of ACTH on blood glucose and hepatic glycogen in dogs.", "content": "The intracisternal administration of ACTH in a dose of 0.2 muU in mongrel dogs produced a significant (P less than 0.001) rise in blood glucose (BGL) and a fall (P less than 0.01) in hepatic glycogen concentration (HGC): in contrast its intravenous administration was devoid of this action. These changes were markedly reduced in the hepatic denervated animals and were completely abolished in animals with spinal cord transectomy. The above changes suggest that ACTH on the intracisternal administration causes a rise in the BGL by an action on the liver through the sympathetic fibers.", "contents": "Effect of intracisternal injection of ACTH on blood glucose and hepatic glycogen in dogs. The intracisternal administration of ACTH in a dose of 0.2 muU in mongrel dogs produced a significant (P less than 0.001) rise in blood glucose (BGL) and a fall (P less than 0.01) in hepatic glycogen concentration (HGC): in contrast its intravenous administration was devoid of this action. These changes were markedly reduced in the hepatic denervated animals and were completely abolished in animals with spinal cord transectomy. The above changes suggest that ACTH on the intracisternal administration causes a rise in the BGL by an action on the liver through the sympathetic fibers."}
{"id": "PMID:231011", "title": "Phagocytosis-induced injury of normal and activated alveolar macrophages.", "content": "The present study tested the hypothesis that BCG-activated macrophages become injured when they phagocytose certain particulates. The data indicate that alveolar macrophages obtained from Mycobacterium bovis BCG-sensitized animals were more susceptible to cell death after in vitro incubation with BCG or zymosan than were macrophages from normal animals. Increased susceptibility was dependent on phagocytosis, since incubation with cytochalasin B, a phagocytosis inhibitor, abrogated the effect. Catalase, cytochrome c, and ascorbic acid offered partial protection to the macrophage, suggesting the involvement of free radicals in the generation of cytotoxicity. Not all of the cells from the alveolar populations were equally susceptible to cell death, thus suggesting either heterogeneity in the cell population or a requirement of more than one cell type in the induction of necrosis or both.", "contents": "Phagocytosis-induced injury of normal and activated alveolar macrophages. The present study tested the hypothesis that BCG-activated macrophages become injured when they phagocytose certain particulates. The data indicate that alveolar macrophages obtained from Mycobacterium bovis BCG-sensitized animals were more susceptible to cell death after in vitro incubation with BCG or zymosan than were macrophages from normal animals. Increased susceptibility was dependent on phagocytosis, since incubation with cytochalasin B, a phagocytosis inhibitor, abrogated the effect. Catalase, cytochrome c, and ascorbic acid offered partial protection to the macrophage, suggesting the involvement of free radicals in the generation of cytotoxicity. Not all of the cells from the alveolar populations were equally susceptible to cell death, thus suggesting either heterogeneity in the cell population or a requirement of more than one cell type in the induction of necrosis or both."}
{"id": "PMID:231012", "title": "Induction of an inhibitor of interferon action in a mouse lymphokine preparation.", "content": "An inhibitor of interferon action was identified in mouse lymphokine preparations. The inhibito was first detected in the supernatant fluid of mouse spleen cells at 72 h after stimulation by staphylococcal enterotoxin A. Inhibitor was not detected in supernatant fluids from unstimulated cultures. This inhibitor blocks the antiviral activity of both immune and fibroblast interferons. The inhibitor was purified 1,000-fold by two-step column chromatography. The partially purified inhibitor blocked the antiviral activity of up to 400 U of interferon. The immunosuppressive effect of interferon was also blocked by the inhibitor, suggesting that the inhibitor may modulate the immunoregulatory function of interferon.", "contents": "Induction of an inhibitor of interferon action in a mouse lymphokine preparation. An inhibitor of interferon action was identified in mouse lymphokine preparations. The inhibito was first detected in the supernatant fluid of mouse spleen cells at 72 h after stimulation by staphylococcal enterotoxin A. Inhibitor was not detected in supernatant fluids from unstimulated cultures. This inhibitor blocks the antiviral activity of both immune and fibroblast interferons. The inhibitor was purified 1,000-fold by two-step column chromatography. The partially purified inhibitor blocked the antiviral activity of up to 400 U of interferon. The immunosuppressive effect of interferon was also blocked by the inhibitor, suggesting that the inhibitor may modulate the immunoregulatory function of interferon."}
{"id": "PMID:231014", "title": "Epstein-Barr virus specific IgA serum antibodies in nasopharyngeal and other respiratory carcinomas.", "content": "In order to better understand the relationship between IgA and IgG antibodies to Epstein-Barr virus (EBV) in nasopharyngeal carcinoma (NPC), we analyzed 230 NPC sera but also a series of sera from patients with other carcinomas selected for their high EBV/IgG antibody titres. We were surprised to find that 21 out of 46 sera from bronchopulmonary carcinomas (BPC) and 6 out of 7 carcinomas of nasal fossae were IgA anti-VCA positive, and 9 BPC sera and 5 nasal fossae sera were also positive for IgA and anti-EA. Bronchial undifferentiated small-cell carcinomas may represent a particular group associated with high EBV profile.", "contents": "Epstein-Barr virus specific IgA serum antibodies in nasopharyngeal and other respiratory carcinomas. In order to better understand the relationship between IgA and IgG antibodies to Epstein-Barr virus (EBV) in nasopharyngeal carcinoma (NPC), we analyzed 230 NPC sera but also a series of sera from patients with other carcinomas selected for their high EBV/IgG antibody titres. We were surprised to find that 21 out of 46 sera from bronchopulmonary carcinomas (BPC) and 6 out of 7 carcinomas of nasal fossae were IgA anti-VCA positive, and 9 BPC sera and 5 nasal fossae sera were also positive for IgA and anti-EA. Bronchial undifferentiated small-cell carcinomas may represent a particular group associated with high EBV profile."}
{"id": "PMID:231015", "title": "Antibody-dependent cell-mediated cytotoxicity against Epstein-Barr virus membrane antigen in African Burkitt's lymphoma.", "content": "Serial samples of sera from patients with African Burkitt's lymphoma were tested for antibody against Epstein-Barr virus (EBV)-specific membrane antigen (MA) by the antibody-dependent cell-mediated cytotoxicity assay (ADCC). Titers of patients in the long-term survivor group were generally higher than those found in the sera of patients in the short-term survivor group. Although ADCC titers to EBV-MA were not useful in predicting which patients would relapse there was a definite relationship between ADCC titer and prognosis. The individual differences in ADCC titers in patients in remission may explain the variability of responses that have been reported in studies on serotherapy with remission plasma.", "contents": "Antibody-dependent cell-mediated cytotoxicity against Epstein-Barr virus membrane antigen in African Burkitt's lymphoma. Serial samples of sera from patients with African Burkitt's lymphoma were tested for antibody against Epstein-Barr virus (EBV)-specific membrane antigen (MA) by the antibody-dependent cell-mediated cytotoxicity assay (ADCC). Titers of patients in the long-term survivor group were generally higher than those found in the sera of patients in the short-term survivor group. Although ADCC titers to EBV-MA were not useful in predicting which patients would relapse there was a definite relationship between ADCC titer and prognosis. The individual differences in ADCC titers in patients in remission may explain the variability of responses that have been reported in studies on serotherapy with remission plasma."}
{"id": "PMID:231018", "title": "Biochemical studies on nickel toxicity in weanling rats -- influence of vitamin C supplementation.", "content": "The influence of high intake of vitamin C in the young growing rats under administration of nickel sulphate in toxic doses has been studied. Ingestion of nickel sulphate depresses the growth rates of rats, alters the vitamin C status in different tissues, inhibits certain enzymes of vitamin C metabolism and changes the activities of alkaline phosphatase and succinic dehydrogenase in the liver and kidney tissues. The acid phosphatase activity of liver, kidney and brain tissues of rats and glucose-6-phosphatase activity in liver, and serum GOT activity were stimulated, with reduction in the in the liver GOT activity. There is stimulation in the activities of rat brain inorganic pyrophosphatase and cholinesterase. Kidney tissues of rats were found to be more susceptible towards nickel toxicity as compared to the hepatic tissues in respect of morphological alterations. There is almost no alteration in the hepatic lipid composition. Administration of vitamin C in high doses to rats fed nickel salts in toxic doses can restore not only the growth rates but also certain enzyme activities to a significant extent.", "contents": "Biochemical studies on nickel toxicity in weanling rats -- influence of vitamin C supplementation. The influence of high intake of vitamin C in the young growing rats under administration of nickel sulphate in toxic doses has been studied. Ingestion of nickel sulphate depresses the growth rates of rats, alters the vitamin C status in different tissues, inhibits certain enzymes of vitamin C metabolism and changes the activities of alkaline phosphatase and succinic dehydrogenase in the liver and kidney tissues. The acid phosphatase activity of liver, kidney and brain tissues of rats and glucose-6-phosphatase activity in liver, and serum GOT activity were stimulated, with reduction in the in the liver GOT activity. There is stimulation in the activities of rat brain inorganic pyrophosphatase and cholinesterase. Kidney tissues of rats were found to be more susceptible towards nickel toxicity as compared to the hepatic tissues in respect of morphological alterations. There is almost no alteration in the hepatic lipid composition. Administration of vitamin C in high doses to rats fed nickel salts in toxic doses can restore not only the growth rates but also certain enzyme activities to a significant extent."}
{"id": "PMID:231021", "title": "Hypercalcemia and elevated parathyroid hormone levels in association with nephroblastoma.", "content": "A three-month-old girl with nephroblastoma had at the same time a hypercalcemia and elevated parathyroid hormone levels. Both biochemical findings disappeared after surgical removal of the tumor.", "contents": "Hypercalcemia and elevated parathyroid hormone levels in association with nephroblastoma. A three-month-old girl with nephroblastoma had at the same time a hypercalcemia and elevated parathyroid hormone levels. Both biochemical findings disappeared after surgical removal of the tumor."}
{"id": "PMID:231028", "title": "Structural investigation of the antibiotic ristomycin A. The amino acid constituents.", "content": "Hydrolysis of the O-methylated aglycone of ristomycin A by a mixture of KOH and NaBH4 yielded a mixture of aromatic amino acids which, after N-acetylation and O-methylation, were separated by chromatography on silica gel. Compounds III approximately VII were isolated and identified by pmr and mass spectroscopy. Compounds V approximately VII were also oxidatively degraded to the corresponding benzoate esters. Componds III and IV are derived from ristomycinic acid (I) and V from actinoidinic acid (II), both of which had been obtained in earlier acid hydrolyses of the antibiotic. Compounds VI and VII had not been detected previously nor glycine which was also found to be a product of base hydrolysis. It is postulated that the new products arise from bisdechlorovancomycinic acid (X). It is concluded that aglycoristomycin A comprises I, II and X which also constitute the aglycone of ristocetin A.", "contents": "Structural investigation of the antibiotic ristomycin A. The amino acid constituents. Hydrolysis of the O-methylated aglycone of ristomycin A by a mixture of KOH and NaBH4 yielded a mixture of aromatic amino acids which, after N-acetylation and O-methylation, were separated by chromatography on silica gel. Compounds III approximately VII were isolated and identified by pmr and mass spectroscopy. Compounds V approximately VII were also oxidatively degraded to the corresponding benzoate esters. Componds III and IV are derived from ristomycinic acid (I) and V from actinoidinic acid (II), both of which had been obtained in earlier acid hydrolyses of the antibiotic. Compounds VI and VII had not been detected previously nor glycine which was also found to be a product of base hydrolysis. It is postulated that the new products arise from bisdechlorovancomycinic acid (X). It is concluded that aglycoristomycin A comprises I, II and X which also constitute the aglycone of ristocetin A."}
{"id": "PMID:231030", "title": "Comparison of Stomacher and Waring Blendor for homogenizing foods to be examined for Clostridium perfringens.", "content": "The Colworth Stomacher Model 400 homogenizer was compared with the Waring Blendor for preparing food homogenates to be examined for Clostridium perfringens. Forty-eight samples representing 6 different food types were inoculated with C. perfringens and examined by the AOAC official first action method for enumeration of C. perfringens in foods. Identical paired specimens of each food type were blended with the 2 devices, and plate counts were made as specified in the official first action method. The effects of frozen storage on plate counts were determined by examining 24 food samples that had been stored for 3 days at -68 degrees C and homogenized both devices. Results of a statistical analysis of the experimental data indicated no significant difference overall (P greater than 0.05) in the plate counts of homogenates prepared with the Waring Blendor or the Stomacher 400, either before or after frozen storage of the food samples. However, the overall plate count average of the 48 samples was slightly higher with the Waring Blendor than with the Stomacher 400 homogenizer.", "contents": "Comparison of Stomacher and Waring Blendor for homogenizing foods to be examined for Clostridium perfringens. The Colworth Stomacher Model 400 homogenizer was compared with the Waring Blendor for preparing food homogenates to be examined for Clostridium perfringens. Forty-eight samples representing 6 different food types were inoculated with C. perfringens and examined by the AOAC official first action method for enumeration of C. perfringens in foods. Identical paired specimens of each food type were blended with the 2 devices, and plate counts were made as specified in the official first action method. The effects of frozen storage on plate counts were determined by examining 24 food samples that had been stored for 3 days at -68 degrees C and homogenized both devices. Results of a statistical analysis of the experimental data indicated no significant difference overall (P greater than 0.05) in the plate counts of homogenates prepared with the Waring Blendor or the Stomacher 400, either before or after frozen storage of the food samples. However, the overall plate count average of the 48 samples was slightly higher with the Waring Blendor than with the Stomacher 400 homogenizer."}
{"id": "PMID:231033", "title": "A double-alpha c-type cytochrome, cytochrome c-555, 549, from an extreme thermophile, Thermus thermophilus HB8.", "content": "A \"double-alpha\" c-type cytochrome, cytochrome c-555, 549, was isolated from the membrane fraction of an extreme thermophile, Thermus thermophilus HB8, and highly purified by chromatographies on DEAE-cellulose and Sephadex G-75 and by isoelectric focusing. The absorption maxima were at 554.8, 548.6, 522, and 417 nm in the reduced form, and at 528, 409, and 360 nm in the oxidized form. The double alpha-peak of this cytochrome was enhanced at liquid nitrogen temperature. The cytochrome contained one heme c group per protein molecule. The isoelectric point, midpoint redox potential and molecular weight were pH 4.0, +0.206 V and about 10,000, respectively. Cytochrome c-555, 549 is highly thermostable.", "contents": "A double-alpha c-type cytochrome, cytochrome c-555, 549, from an extreme thermophile, Thermus thermophilus HB8. A \"double-alpha\" c-type cytochrome, cytochrome c-555, 549, was isolated from the membrane fraction of an extreme thermophile, Thermus thermophilus HB8, and highly purified by chromatographies on DEAE-cellulose and Sephadex G-75 and by isoelectric focusing. The absorption maxima were at 554.8, 548.6, 522, and 417 nm in the reduced form, and at 528, 409, and 360 nm in the oxidized form. The double alpha-peak of this cytochrome was enhanced at liquid nitrogen temperature. The cytochrome contained one heme c group per protein molecule. The isoelectric point, midpoint redox potential and molecular weight were pH 4.0, +0.206 V and about 10,000, respectively. Cytochrome c-555, 549 is highly thermostable."}
{"id": "PMID:231034", "title": "Stereospecificity of peptidyl dipeptide hydrolase (angiotensin I-converting enzyme).", "content": "The stereospecificity of peptidyl dipeptide hydrolase [EC 3.4.15.1] was investigated. Six free and N-blocked alanyl peptides containing D-alanine were synthesized and tested as substrates. Their susceptibilities were determined by measuring Ala-Ala release by cation exchange column chromatography. Their Michaelis constants, Km values, and velocity maxima, Vmax values, were also determined. The enzyme showed high stereospecificity for an amino acyl residue in position 3 from C-terminus: it had an absolute requirement for the alanyl residue of the L-configuration in this position. An alanyl residue of the L-configuration in position 1 or 2 increased, but was not essential for activity. The enzyme showed little stereospecificity for an alanyl residue in position 4 from the C-terminus.", "contents": "Stereospecificity of peptidyl dipeptide hydrolase (angiotensin I-converting enzyme). The stereospecificity of peptidyl dipeptide hydrolase [EC 3.4.15.1] was investigated. Six free and N-blocked alanyl peptides containing D-alanine were synthesized and tested as substrates. Their susceptibilities were determined by measuring Ala-Ala release by cation exchange column chromatography. Their Michaelis constants, Km values, and velocity maxima, Vmax values, were also determined. The enzyme showed high stereospecificity for an amino acyl residue in position 3 from C-terminus: it had an absolute requirement for the alanyl residue of the L-configuration in this position. An alanyl residue of the L-configuration in position 1 or 2 increased, but was not essential for activity. The enzyme showed little stereospecificity for an alanyl residue in position 4 from the C-terminus."}
{"id": "PMID:231035", "title": "Concanavalin A-induced increase in the membrane fluidity of chicken erythrocytes.", "content": "To determine the fluidity of the membrane lipid phase, chicken erythrocytes were labeled with a stearic acid derivative spin label. When chicken erythrocytes were treated with concanavalin A (Con A), ESR spectra showed a change in the peaks of the labels in membrane lipids, indicating an increase of membrane fluidity. The degree of the increase in fluidity of the membrane lipid phase depended on the valency of the lectin used. Tetravalent Con A induced an increase of membrane fluidity at a concentration as low as 30 micrograms/ml, while a monovalent derivative of Con A did not affect membrane fluidity. This increase in membrane fluidity was observed within 10 min after the addition of Con A. If bound Con A was removed with methyl alpha-D-mannoside later than 60 min after its addition, a complete return of the fluidity to the normal level could not be observed. However, no change was found in the composition of phospholipids or in the fatty acid compositions of phosphatidylcholine and phosphatidylethanolamine of chicken erythrocytes after the addition of Con A, indicating that this increase in membrane fluidity is not caused by a change of lipid composition. The clustering of membrane receptors of chicken erythrocytes for Con A was demonstrated when the two-dimensional distribution of ferritin-conjugated Con A on the membranes was assayed by transmission electron microscopy. Furthermore, it was shown that major receptors for Con A of chicken erythrocytes were transmembrane glycoproteins having apparent molecular weights of 100K, 45, and 33K.", "contents": "Concanavalin A-induced increase in the membrane fluidity of chicken erythrocytes. To determine the fluidity of the membrane lipid phase, chicken erythrocytes were labeled with a stearic acid derivative spin label. When chicken erythrocytes were treated with concanavalin A (Con A), ESR spectra showed a change in the peaks of the labels in membrane lipids, indicating an increase of membrane fluidity. The degree of the increase in fluidity of the membrane lipid phase depended on the valency of the lectin used. Tetravalent Con A induced an increase of membrane fluidity at a concentration as low as 30 micrograms/ml, while a monovalent derivative of Con A did not affect membrane fluidity. This increase in membrane fluidity was observed within 10 min after the addition of Con A. If bound Con A was removed with methyl alpha-D-mannoside later than 60 min after its addition, a complete return of the fluidity to the normal level could not be observed. However, no change was found in the composition of phospholipids or in the fatty acid compositions of phosphatidylcholine and phosphatidylethanolamine of chicken erythrocytes after the addition of Con A, indicating that this increase in membrane fluidity is not caused by a change of lipid composition. The clustering of membrane receptors of chicken erythrocytes for Con A was demonstrated when the two-dimensional distribution of ferritin-conjugated Con A on the membranes was assayed by transmission electron microscopy. Furthermore, it was shown that major receptors for Con A of chicken erythrocytes were transmembrane glycoproteins having apparent molecular weights of 100K, 45, and 33K."}
{"id": "PMID:231036", "title": "Regulation of phosphodiesterase and ornithine decarboxylase by cAMP is cell cycle independent.", "content": "Cyclic AMP (cAMP) causes growth arrest in G1 and induction of cAMP phosphodiesterase and decrease of ornithine decarboxylase in S49 mouse lymphoma cells. Dibutyryl cAMP treatment of partially synchronized cells causes similar changes in activities of both enzymes, regardless of position in the cell cycle. This suggests that cAMP regulation of these enzymes is not mediated by growth perturbation.", "contents": "Regulation of phosphodiesterase and ornithine decarboxylase by cAMP is cell cycle independent. Cyclic AMP (cAMP) causes growth arrest in G1 and induction of cAMP phosphodiesterase and decrease of ornithine decarboxylase in S49 mouse lymphoma cells. Dibutyryl cAMP treatment of partially synchronized cells causes similar changes in activities of both enzymes, regardless of position in the cell cycle. This suggests that cAMP regulation of these enzymes is not mediated by growth perturbation."}
{"id": "PMID:231037", "title": "A variant vascular endothelial cell line with altered growth characteristics.", "content": "A variant endothelial cell type was found to arise spontaneously from cultures of bovine aortal endothelial cells. This variant showed no contact inhibition and overgrew confluent cultures of wild-type endothelial cells. Unlike other reported variants of this cell type produced by chemical mutagenesis or by withdrawal of polypeptide growth factor, this variant retained the capacity to synthesis factor VIII antigen, but showed no alteration from wild-type in capacity to adsorb platelets. The variant also had an increased capacity to bind FITC-conjugated con A to its surface.", "contents": "A variant vascular endothelial cell line with altered growth characteristics. A variant endothelial cell type was found to arise spontaneously from cultures of bovine aortal endothelial cells. This variant showed no contact inhibition and overgrew confluent cultures of wild-type endothelial cells. Unlike other reported variants of this cell type produced by chemical mutagenesis or by withdrawal of polypeptide growth factor, this variant retained the capacity to synthesis factor VIII antigen, but showed no alteration from wild-type in capacity to adsorb platelets. The variant also had an increased capacity to bind FITC-conjugated con A to its surface."}
{"id": "PMID:231038", "title": "Growth-promoting actions of extracts from mouse submaxillary glands on human endothelial cells in culture.", "content": "Extracts of submaxillary glands from two different strains of inbred mice were mitogenic for human endothelial cells in culture. The mitogenic activity of extracts from glands of males of the SWR/J and C57BL/10J strains were equivalent, and the growth stimulating effect was unrelated to renin or esteroproteolytic activity. Mitogenic activity in extracts from SWR/J females was less than that from males, and extracts from C57BL/10J females were inactive. The polypeptide growth factors, epidermal (EGF) and fibroblast (FGF) growth factors, also stimulated replication of endothelial cells. Cells from either umbilical arteries or veins responded to submaxillary extracts, EGF, or FGF with a similar increase in cell number, increase in protein and enhanced uptake of 3H-thymidine. The proliferative response was associated with decreased activity of angiotensin I converting enzyme which is localized on the endothelial surface. Nerve growth factor (NGF) was not mitogenic for endothelial cells. Extracts of submaxillary glands from male mice of either strain contained approximately 20 times more EGF than extracts from females, as determined by immunodiffusion. Mitogenic activity of the extracts was completely inhibited by antiserum to EGF, suggesting that the active component of these preparations is EGF.", "contents": "Growth-promoting actions of extracts from mouse submaxillary glands on human endothelial cells in culture. Extracts of submaxillary glands from two different strains of inbred mice were mitogenic for human endothelial cells in culture. The mitogenic activity of extracts from glands of males of the SWR/J and C57BL/10J strains were equivalent, and the growth stimulating effect was unrelated to renin or esteroproteolytic activity. Mitogenic activity in extracts from SWR/J females was less than that from males, and extracts from C57BL/10J females were inactive. The polypeptide growth factors, epidermal (EGF) and fibroblast (FGF) growth factors, also stimulated replication of endothelial cells. Cells from either umbilical arteries or veins responded to submaxillary extracts, EGF, or FGF with a similar increase in cell number, increase in protein and enhanced uptake of 3H-thymidine. The proliferative response was associated with decreased activity of angiotensin I converting enzyme which is localized on the endothelial surface. Nerve growth factor (NGF) was not mitogenic for endothelial cells. Extracts of submaxillary glands from male mice of either strain contained approximately 20 times more EGF than extracts from females, as determined by immunodiffusion. Mitogenic activity of the extracts was completely inhibited by antiserum to EGF, suggesting that the active component of these preparations is EGF."}
{"id": "PMID:231039", "title": "Induction of an oligodendroglial enzyme in C-6 glioma cells maintained at high density or in serum-free medium.", "content": "The relationship between cell density and the activity of 2':3'-cyclic nucleotide 3'-phosphohydrolase (CNP), an enzyme believed to be specific to oligodendroglial cells and myelin in the brain, has been studied in cultured C-6 glioma cells. Over a 12-day period, the specific activity of CNP underwent a 4-fold increase in conjunction with an increase in the cell density (total protein/flask) and a decline in the growth rate of the cultures. In contrast, the specific activity of Na+,K+-ATPase was not influenced by cell density. Experiments with cultures seeded at different initial densities indicated that the increase in CNP activity coincided with the attainment of a specific cell density rather than with the length of time that the cells were maintained in culture. Arrest of cell proliferation in non-confluent C-6 cells by means of thymidine blockade was not sufficient to cause an increase in the activity of CNP; however, removal of serum from the culture medium resulted in a 3-fold induction of the enzyme in the absence of a high degree of cell contact. The induction of CNP in cells maintained in serum-free medium paralleled the development of a series of distinct morphological changes reminiscent of glial differentiation, which occurred within 48 hours after removal of the serum. Inhibition of protein synthesis by cycloheximide prevented the induction of CNP in serum-free cultures. The demonstration that an enhancement of an oligodendroglial characteristic in C-6 glioma cells can be obtained by growing the cells to high density or by removing serum from the medium, provides further support for the suggestion that these cells may be analogous to the glial stem cells present in the developing brain.", "contents": "Induction of an oligodendroglial enzyme in C-6 glioma cells maintained at high density or in serum-free medium. The relationship between cell density and the activity of 2':3'-cyclic nucleotide 3'-phosphohydrolase (CNP), an enzyme believed to be specific to oligodendroglial cells and myelin in the brain, has been studied in cultured C-6 glioma cells. Over a 12-day period, the specific activity of CNP underwent a 4-fold increase in conjunction with an increase in the cell density (total protein/flask) and a decline in the growth rate of the cultures. In contrast, the specific activity of Na+,K+-ATPase was not influenced by cell density. Experiments with cultures seeded at different initial densities indicated that the increase in CNP activity coincided with the attainment of a specific cell density rather than with the length of time that the cells were maintained in culture. Arrest of cell proliferation in non-confluent C-6 cells by means of thymidine blockade was not sufficient to cause an increase in the activity of CNP; however, removal of serum from the culture medium resulted in a 3-fold induction of the enzyme in the absence of a high degree of cell contact. The induction of CNP in cells maintained in serum-free medium paralleled the development of a series of distinct morphological changes reminiscent of glial differentiation, which occurred within 48 hours after removal of the serum. Inhibition of protein synthesis by cycloheximide prevented the induction of CNP in serum-free cultures. The demonstration that an enhancement of an oligodendroglial characteristic in C-6 glioma cells can be obtained by growing the cells to high density or by removing serum from the medium, provides further support for the suggestion that these cells may be analogous to the glial stem cells present in the developing brain."}
{"id": "PMID:231040", "title": "Phenotypic characterization of ouabain-resistant Aedes albopictus cells.", "content": "The phenotype of a ouabain-resistant Aedes albopictus cell line has been partially characterized. Treatment of ouabain-sensitive cells with 0.005-1.0 mM ouabain resulted in an 80% reduction in the uptake of 86rubidium (86Rb+), an ion with an affinity for the K+ pump binding site; ouabain-resistant cells showed only a 40% reduction with 1.0 mM ouabain. When ouabain-sensitive cells were incubated in the presence of ouabain (0.1 mM) for one and one-half to three hours, the molar ratio of intracellular Na+/K+ rose from 0.2 to 4.2. In ouabain-resistant cells, a similar treatment had very little effect. Based on [3H] ouabain-binding studies, ouabain-resistant cells were estimated to have 60% fewer binding sites per cell than ouabain-sensitive cells. The spontaneous mutation rate from ouabain sensitivity to ouabain resistance was calculated to be 1-6 x 10(-8) mutations/cell/generation, a value similar to that reported for mammalian cells at the analogous locus.", "contents": "Phenotypic characterization of ouabain-resistant Aedes albopictus cells. The phenotype of a ouabain-resistant Aedes albopictus cell line has been partially characterized. Treatment of ouabain-sensitive cells with 0.005-1.0 mM ouabain resulted in an 80% reduction in the uptake of 86rubidium (86Rb+), an ion with an affinity for the K+ pump binding site; ouabain-resistant cells showed only a 40% reduction with 1.0 mM ouabain. When ouabain-sensitive cells were incubated in the presence of ouabain (0.1 mM) for one and one-half to three hours, the molar ratio of intracellular Na+/K+ rose from 0.2 to 4.2. In ouabain-resistant cells, a similar treatment had very little effect. Based on [3H] ouabain-binding studies, ouabain-resistant cells were estimated to have 60% fewer binding sites per cell than ouabain-sensitive cells. The spontaneous mutation rate from ouabain sensitivity to ouabain resistance was calculated to be 1-6 x 10(-8) mutations/cell/generation, a value similar to that reported for mammalian cells at the analogous locus."}
{"id": "PMID:231041", "title": "Yolk transport in the ovarian follicle of the hen (Gallus domesticus): lipoprotein-like particles at the periphery of the oocyte in the rapid growth phase.", "content": "Thin sections of the oocyte periphery and surrounding granulosa layer from 1--5 day preovulatory follicles were examined by transmission electron microscopy. With the use of certain procedures in tissue preparation, notably the tannic acid method, numerous particles in the range of 15--40 nm with a mean diameter of 27 nm were observed in both extra- and intracellularly. The particles were abundant in the granulosa basal lamina, in the spaces between the granulosa cells and in the perivitelline space. They appeared to adhere to the oolemma as a continuous double layer which was also observed to line the coated vesicles, 200--350 nm in diameter, invaginating from the oolemma. The layer of particles was not found on the plasma membranes of the granulosa cells, nor were particles present within the cells. In the peripheral cytoplasm of the oocyte the yolk spheres, ranging upwards from 250 nm diameter, were membrane-bound and contained tightly packed particles similar to those on the oolemma. Bodies displaying features intermediate between coated vesicles and yolk spheres suggested that, on entry into the cell, loss of the cytoplasmic coat and obliteration of the vesicular lumen gave rise to nascent yolk spheres which then fused together to form the larger spheres. The extracellular layer, coated vesicles and smaller yolk spheres were absent in oocytes fixed after a 10-min delay. The evidence indicated that 27-nm particles were transferred from the basal lamina to the oocyte surface via the intergranulosa cell channels, incorporated into the cell by adsorptive endocytosis and then transferred to the yolk spheres with little morphological alteration. The identity of the particles with very low density lipoproteins, the major components of the yolk solids, was discussed.", "contents": "Yolk transport in the ovarian follicle of the hen (Gallus domesticus): lipoprotein-like particles at the periphery of the oocyte in the rapid growth phase. Thin sections of the oocyte periphery and surrounding granulosa layer from 1--5 day preovulatory follicles were examined by transmission electron microscopy. With the use of certain procedures in tissue preparation, notably the tannic acid method, numerous particles in the range of 15--40 nm with a mean diameter of 27 nm were observed in both extra- and intracellularly. The particles were abundant in the granulosa basal lamina, in the spaces between the granulosa cells and in the perivitelline space. They appeared to adhere to the oolemma as a continuous double layer which was also observed to line the coated vesicles, 200--350 nm in diameter, invaginating from the oolemma. The layer of particles was not found on the plasma membranes of the granulosa cells, nor were particles present within the cells. In the peripheral cytoplasm of the oocyte the yolk spheres, ranging upwards from 250 nm diameter, were membrane-bound and contained tightly packed particles similar to those on the oolemma. Bodies displaying features intermediate between coated vesicles and yolk spheres suggested that, on entry into the cell, loss of the cytoplasmic coat and obliteration of the vesicular lumen gave rise to nascent yolk spheres which then fused together to form the larger spheres. The extracellular layer, coated vesicles and smaller yolk spheres were absent in oocytes fixed after a 10-min delay. The evidence indicated that 27-nm particles were transferred from the basal lamina to the oocyte surface via the intergranulosa cell channels, incorporated into the cell by adsorptive endocytosis and then transferred to the yolk spheres with little morphological alteration. The identity of the particles with very low density lipoproteins, the major components of the yolk solids, was discussed."}
{"id": "PMID:231042", "title": "Electron-microscopy of intact nuclear DNA from human cells.", "content": "Structures retaining many of the morphological features of nuclei may be released by lysing human cells in a non-ionic detergent and 2 M NaCl. Such nucleoids contain all the nuclear DNA packaged within a flexible cage of RNA and protein. HeLa nucleoids have been spread at an air-water interface and viewed in the electron microscope. A tangled network of superhelical fibres surrounds the collapsed cage. Irradiation with gamma-rays abolishes supercoiling and treatment with the untwisting enzyme or a low concentration of ethidium reduces it. A high concentration of ethidium induces supertwisting. The nuclear DNA of higher cells can be isolated naked, supercoiled and intact.", "contents": "Electron-microscopy of intact nuclear DNA from human cells. Structures retaining many of the morphological features of nuclei may be released by lysing human cells in a non-ionic detergent and 2 M NaCl. Such nucleoids contain all the nuclear DNA packaged within a flexible cage of RNA and protein. HeLa nucleoids have been spread at an air-water interface and viewed in the electron microscope. A tangled network of superhelical fibres surrounds the collapsed cage. Irradiation with gamma-rays abolishes supercoiling and treatment with the untwisting enzyme or a low concentration of ethidium reduces it. A high concentration of ethidium induces supertwisting. The nuclear DNA of higher cells can be isolated naked, supercoiled and intact."}
{"id": "PMID:231044", "title": "High-performance liquid chromatographic assay for acid and alkaline phosphatase in serum.", "content": "High-performance liquid chromatography was used to assay serum acid and alkaline phosphatase. Samples were incubated with adenosine-5'-monophosphoric acid (AMP) in a buffer of required pH, 5'-nucleotidase was inhibited with Ni2+ ions, and the phosphatase activity was determined by measuring the concentration of the reaction product, adenosine. The analysis time, after the incubation is terminated, is short (7 min), and the assay is quantitative and reproducible. Complete separation of the reaction product from the substrate and the naturally occurring serum constituents and the high sensitivity of the ultraviolet detection system eliminate some of the problems commonly encountered in spectrophotometric assays.", "contents": "High-performance liquid chromatographic assay for acid and alkaline phosphatase in serum. High-performance liquid chromatography was used to assay serum acid and alkaline phosphatase. Samples were incubated with adenosine-5'-monophosphoric acid (AMP) in a buffer of required pH, 5'-nucleotidase was inhibited with Ni2+ ions, and the phosphatase activity was determined by measuring the concentration of the reaction product, adenosine. The analysis time, after the incubation is terminated, is short (7 min), and the assay is quantitative and reproducible. Complete separation of the reaction product from the substrate and the naturally occurring serum constituents and the high sensitivity of the ultraviolet detection system eliminate some of the problems commonly encountered in spectrophotometric assays."}
{"id": "PMID:231046", "title": "Stability-indicating assay for pivmecillinam hydrochloride and pivmecillinam hydrochloride capsules.", "content": "A high-pressure liquid chromatographic assay has been developed for pivmecillinam hydrochloride and pivmecillinam hydrochloride capsules. The method separates five reported degradation products and a number of esterified, related compounds. The accuracy of this method is comparable to the published ultraviolet assay and the relative standard deviation of a series of six replicate assays was better than +/- 0.7%.", "contents": "Stability-indicating assay for pivmecillinam hydrochloride and pivmecillinam hydrochloride capsules. A high-pressure liquid chromatographic assay has been developed for pivmecillinam hydrochloride and pivmecillinam hydrochloride capsules. The method separates five reported degradation products and a number of esterified, related compounds. The accuracy of this method is comparable to the published ultraviolet assay and the relative standard deviation of a series of six replicate assays was better than +/- 0.7%."}
{"id": "PMID:231047", "title": "Use of protein A-treated sera in unmasking herpes simplex virus type 1 (HSV-1) immunoglobulin A and identifying HSV-1 immunoglobulin G as the predominant neutralizing antibody.", "content": "Treatment of human sera with protein A reduced the amounts of immunoglobulin G (IgG), IgA, and IgM detected by radial immunodiffusion. This treatment also decreased the amount of herpes-specific IgG and IgM detected by radioimmunoassay, whereas it increased and even unmasked the amount of herpes-specific IgA detected. Comparison of protein A-treated sera with untreated sera indicated that herpes simplex virus type 1 IgG was responsible for more than 92 to 99% of the serum neutralizing activity.", "contents": "Use of protein A-treated sera in unmasking herpes simplex virus type 1 (HSV-1) immunoglobulin A and identifying HSV-1 immunoglobulin G as the predominant neutralizing antibody. Treatment of human sera with protein A reduced the amounts of immunoglobulin G (IgG), IgA, and IgM detected by radial immunodiffusion. This treatment also decreased the amount of herpes-specific IgG and IgM detected by radioimmunoassay, whereas it increased and even unmasked the amount of herpes-specific IgA detected. Comparison of protein A-treated sera with untreated sera indicated that herpes simplex virus type 1 IgG was responsible for more than 92 to 99% of the serum neutralizing activity."}
{"id": "PMID:231048", "title": "Enzyme-linked protein A: an enzyme-linked immunosorbent assay reagent for detection of human immunoglobulin G and virus-specific antibody.", "content": "A general-purpose reagent capable of reacting with immunoglobulin G in a modified enzyme-linked immunosorbent assay technique was prepared by using protein A coupled with horseradish peroxidase. The reagent detected low levels (0.003 to 1.0 microgram/ml) of human immunoglobulin G and was also applied in an enzyme-linked immunosorbent assay for titration of antibody to human cytomegalovirus. The antibody titers to human cytomegalovirus determined by enzyme-linked immunosorbent assay and by complement fixation were compared. The correlation coefficient between the two techniques was 0.85, but the enzyme-linked immunosorbent assay was 10 times more sensitive than complement fixation in terms of antibody titers detected.", "contents": "Enzyme-linked protein A: an enzyme-linked immunosorbent assay reagent for detection of human immunoglobulin G and virus-specific antibody. A general-purpose reagent capable of reacting with immunoglobulin G in a modified enzyme-linked immunosorbent assay technique was prepared by using protein A coupled with horseradish peroxidase. The reagent detected low levels (0.003 to 1.0 microgram/ml) of human immunoglobulin G and was also applied in an enzyme-linked immunosorbent assay for titration of antibody to human cytomegalovirus. The antibody titers to human cytomegalovirus determined by enzyme-linked immunosorbent assay and by complement fixation were compared. The correlation coefficient between the two techniques was 0.85, but the enzyme-linked immunosorbent assay was 10 times more sensitive than complement fixation in terms of antibody titers detected."}
{"id": "PMID:231049", "title": "Comparison of rates of virus isolation from leukocyte populations separated from blood by conventional and Ficoll-Paque/Macrodex methods.", "content": "One hundred fifty-two blood specimens, largely from immunocompromised patients, were collected in heparinized Vacutainer tubes and divided into paired aliquots of equal volume. Buffy-coat preparations, containing mixed leukocyte and separate mononuclear and polymorphonuclear leukocyte populations were obtained by treatment of blood with conventional and Ficoll-Paque/Macrodex (F-P/M) methods. The development of cytopathic effect in monolayers of WI-38 fibroblasts inoculated with cell suspensions derived from the two methods was used to assess virus infectivity. Twice as many virus isolations were obtained using F-P/M. Of those viruses isolated by both conventional and F-P/M, the development of cytopathic effect was more extensive using the latter method. Moreover, a greater variety of viruses was isolated using F-P/M method, as compared to the conventional method. The F-P/M method is no more time consuming than conventional procedures, is readily adaptable for use in the diagnostic virology laboratory, requires only minimal additional cost, and is a particularly suitable and effective means of monitoring viremia.", "contents": "Comparison of rates of virus isolation from leukocyte populations separated from blood by conventional and Ficoll-Paque/Macrodex methods. One hundred fifty-two blood specimens, largely from immunocompromised patients, were collected in heparinized Vacutainer tubes and divided into paired aliquots of equal volume. Buffy-coat preparations, containing mixed leukocyte and separate mononuclear and polymorphonuclear leukocyte populations were obtained by treatment of blood with conventional and Ficoll-Paque/Macrodex (F-P/M) methods. The development of cytopathic effect in monolayers of WI-38 fibroblasts inoculated with cell suspensions derived from the two methods was used to assess virus infectivity. Twice as many virus isolations were obtained using F-P/M. Of those viruses isolated by both conventional and F-P/M, the development of cytopathic effect was more extensive using the latter method. Moreover, a greater variety of viruses was isolated using F-P/M method, as compared to the conventional method. The F-P/M method is no more time consuming than conventional procedures, is readily adaptable for use in the diagnostic virology laboratory, requires only minimal additional cost, and is a particularly suitable and effective means of monitoring viremia."}
{"id": "PMID:231050", "title": "Enteric adenoviruses: detection, replication, and significance.", "content": "Adenoviruses can be demonstrated readily in the stools of pediatric gastroenteritis patients by electron microscopy or counterimmunoelectrophoresis, but in 45% of these cases the virus will not grow in cell culture. Indirect immunofluorescence microscopy can be used to detect nongrowing strains of adenovirus; these strains have a unique single-cell fluorescence pattern. Hematoxylin and eosin staining reveals adenovirus-like inclusion bodies in the same distribution as fluorescent cells. Pretreatment of nongrowing adenovirus with convalescent-phase patient serum neutralized its ability to infect the cell culture and produce fluorescent cells. Indirect immunofluorescence microscopy compared favorably with electron microscopy in demonstrating virus in the stools of patients.", "contents": "Enteric adenoviruses: detection, replication, and significance. Adenoviruses can be demonstrated readily in the stools of pediatric gastroenteritis patients by electron microscopy or counterimmunoelectrophoresis, but in 45% of these cases the virus will not grow in cell culture. Indirect immunofluorescence microscopy can be used to detect nongrowing strains of adenovirus; these strains have a unique single-cell fluorescence pattern. Hematoxylin and eosin staining reveals adenovirus-like inclusion bodies in the same distribution as fluorescent cells. Pretreatment of nongrowing adenovirus with convalescent-phase patient serum neutralized its ability to infect the cell culture and produce fluorescent cells. Indirect immunofluorescence microscopy compared favorably with electron microscopy in demonstrating virus in the stools of patients."}
{"id": "PMID:231051", "title": "Lipoproteins as substitutes for serum in Mycoplasma culture medium.", "content": "Crude lipoprotein-containing fractions obtained from sera of three different animal species were tested, in combination with bovine serum in Mycoplasma pneumoniae culture medium. All sera yielded at least one lipoprotein-containing component which was considerably more effective in promoting mycoplasma growth than the unfractionated serum sample from which it was derived. The very low activity of certain whole-serum samples tested in this investigation suggests that toxic substances may be present in whole serum which are not contained in the lipoprotein preparations. The greatest activity appeared in the high-density lipoprotein-containing components of bovine and horse sera and the low-density lipoprotein-containing components of human serum. The high degree of growth-supporting activity of these crude lipoprotein-containing serum components suggests that they may be useful as serum substitutes in mycoplasma culture media.", "contents": "Lipoproteins as substitutes for serum in Mycoplasma culture medium. Crude lipoprotein-containing fractions obtained from sera of three different animal species were tested, in combination with bovine serum in Mycoplasma pneumoniae culture medium. All sera yielded at least one lipoprotein-containing component which was considerably more effective in promoting mycoplasma growth than the unfractionated serum sample from which it was derived. The very low activity of certain whole-serum samples tested in this investigation suggests that toxic substances may be present in whole serum which are not contained in the lipoprotein preparations. The greatest activity appeared in the high-density lipoprotein-containing components of bovine and horse sera and the low-density lipoprotein-containing components of human serum. The high degree of growth-supporting activity of these crude lipoprotein-containing serum components suggests that they may be useful as serum substitutes in mycoplasma culture media."}
{"id": "PMID:231052", "title": "Enzyme-linked immunosorbent assay for detection of antibodies to murine hepatitis virus.", "content": "An enzyme-linked immunosorbent assay was developed for the detection of antibodies to murine hepatitis virus. A high prevalence of antibody to murine hepatitis virus was found by the enzyme-linked immunosorbent assay in colonies with a low prevalence of complement-fixing antibodies. Murine hepatitis virus strain A59 was found to be broadly reactive as an enzyme-linked immunosorbent assay antigen.", "contents": "Enzyme-linked immunosorbent assay for detection of antibodies to murine hepatitis virus. An enzyme-linked immunosorbent assay was developed for the detection of antibodies to murine hepatitis virus. A high prevalence of antibody to murine hepatitis virus was found by the enzyme-linked immunosorbent assay in colonies with a low prevalence of complement-fixing antibodies. Murine hepatitis virus strain A59 was found to be broadly reactive as an enzyme-linked immunosorbent assay antigen."}
{"id": "PMID:231062", "title": "Effects of somatostatin on insulin and glucagon in patients with insulinoma.", "content": "Effects of somatostatin on fasting and arginine-or tolbutamide-stimulated insulin release were studied in four patients with insulinoma. Somatostatin (bolus or bolus + infusion) reduced fasting insulin values in all patients; insulin response to tolbutamide was partially reduced in two patients; somatostatin bolus impaired the insulin response to arginine. Fasting glucagon levels and glucagon response to arginine were also reduced by somatostatin. These results indicate the potential usefulness of somatostatin in the diagnosis of insulinoma even if its effect on insulin is only partial.", "contents": "Effects of somatostatin on insulin and glucagon in patients with insulinoma. Effects of somatostatin on fasting and arginine-or tolbutamide-stimulated insulin release were studied in four patients with insulinoma. Somatostatin (bolus or bolus + infusion) reduced fasting insulin values in all patients; insulin response to tolbutamide was partially reduced in two patients; somatostatin bolus impaired the insulin response to arginine. Fasting glucagon levels and glucagon response to arginine were also reduced by somatostatin. These results indicate the potential usefulness of somatostatin in the diagnosis of insulinoma even if its effect on insulin is only partial."}
{"id": "PMID:231064", "title": "Insulinoma: clinical manifestations, diagnosis and treatment. The significance of the prolonged fasting test and of the fasting blood glucose-insulin relationship.", "content": "This paper describes the clinical manifestations and the significance of the fasting blood glucose-insulin relationship and the prolonged fasting test in the diagnosis of insulinoma. Pre-and postoperative results are reported. In addition, a description is given of the angiographic demonstration and the results of the surgical removal of the insulinomas.", "contents": "Insulinoma: clinical manifestations, diagnosis and treatment. The significance of the prolonged fasting test and of the fasting blood glucose-insulin relationship. This paper describes the clinical manifestations and the significance of the fasting blood glucose-insulin relationship and the prolonged fasting test in the diagnosis of insulinoma. Pre-and postoperative results are reported. In addition, a description is given of the angiographic demonstration and the results of the surgical removal of the insulinomas."}
{"id": "PMID:231067", "title": "Epidemiological, clinical, and pathomorphological characteristics of epidemic poliomyelitis-like disease caused by enterovirus 71.", "content": "In May-September, 1975, an outbreak of epidemic disease clinically and pathomorphologically simulating nearly all known forms of poliomyelitis occurred predominantly among young infants in Bulgaria. Most cases presented benign aseptic meningitis, sometimes with a short period of general cerebra- symptoms. Paralytic forms, such as bulbar polioencephalitis, anterior poliomyelitis, isolated pareses of the facial nerve, occasional cases of encephalomyocarditis, etc., were observed in about 21% of all cases. Over one-fourth of the paralytic cases with bulbar symptoms ended fatally. In March, 1976 another sporadic fatal case of this disease was examined. No new cases occurred in 1977. Histopathological examinations in all fatal cases regularly revealed lesions in the grey matter of the medulla and spinal cord typical of acute anterior poliomyelitis and bulbar polioencephalitis, with some peculiar features of localization and depth of the involvement of the brain stem. The similarity to poliomyelitis and precariously rapid increase in the incidence led to the decision to urgently vaccinate the entire human population with Sabin's live poliovirus vaccine simultaneously in the whole country in order to produce interference with the circulating agent. This aim appeared to have been achieved partially because soon the number of new cases of the disease began to decrease; however, no sharp and complete break in the curve of the incidence occurred. By the time of mass vaccination, the results of virological examinations started before were not yet available. Later, comprehensive complete evidence was obtained that over 25 fatal and many other typical cases of the disease were associated with an enterovirus proved to be antigenically related to enterovirus 71. The diseases in Bulgaria, 1975, differ considerably in the frequency of paralytic forms and in severity from the epidemics caused by enterovirus 71 in Sweden, 1973, Australia, 1972--1973, USA, 1969--1972, and Japan, 1972--1973.", "contents": "Epidemiological, clinical, and pathomorphological characteristics of epidemic poliomyelitis-like disease caused by enterovirus 71. In May-September, 1975, an outbreak of epidemic disease clinically and pathomorphologically simulating nearly all known forms of poliomyelitis occurred predominantly among young infants in Bulgaria. Most cases presented benign aseptic meningitis, sometimes with a short period of general cerebra- symptoms. Paralytic forms, such as bulbar polioencephalitis, anterior poliomyelitis, isolated pareses of the facial nerve, occasional cases of encephalomyocarditis, etc., were observed in about 21% of all cases. Over one-fourth of the paralytic cases with bulbar symptoms ended fatally. In March, 1976 another sporadic fatal case of this disease was examined. No new cases occurred in 1977. Histopathological examinations in all fatal cases regularly revealed lesions in the grey matter of the medulla and spinal cord typical of acute anterior poliomyelitis and bulbar polioencephalitis, with some peculiar features of localization and depth of the involvement of the brain stem. The similarity to poliomyelitis and precariously rapid increase in the incidence led to the decision to urgently vaccinate the entire human population with Sabin's live poliovirus vaccine simultaneously in the whole country in order to produce interference with the circulating agent. This aim appeared to have been achieved partially because soon the number of new cases of the disease began to decrease; however, no sharp and complete break in the curve of the incidence occurred. By the time of mass vaccination, the results of virological examinations started before were not yet available. Later, comprehensive complete evidence was obtained that over 25 fatal and many other typical cases of the disease were associated with an enterovirus proved to be antigenically related to enterovirus 71. The diseases in Bulgaria, 1975, differ considerably in the frequency of paralytic forms and in severity from the epidemics caused by enterovirus 71 in Sweden, 1973, Australia, 1972--1973, USA, 1969--1972, and Japan, 1972--1973."}
{"id": "PMID:231063", "title": "Influence of magnesium on the secretion and action of parathyroid hormone.", "content": "The interactions of serum levels of magnesium and parathyroid hormone (PTH) have been studied in a patient with hypomagnesemia and hypocalcemia following intestinal bypass surgery for obesity. When serum magnesium was low serum PTH was not stimulated by hypocalcemia. With correction of magnesium deficiency hypocalcemia was associated with elevation of serum PTH levels. Infusion of exogenous PTH induced a clearly detectable renal response in the presence of hypomagnesemia but the response was diminished when serum magnesium was elevated. In this patient it appears that hypomagnesemia suppressed parathyroid gland activity, leaving the renal action of PTH intact.", "contents": "Influence of magnesium on the secretion and action of parathyroid hormone. The interactions of serum levels of magnesium and parathyroid hormone (PTH) have been studied in a patient with hypomagnesemia and hypocalcemia following intestinal bypass surgery for obesity. When serum magnesium was low serum PTH was not stimulated by hypocalcemia. With correction of magnesium deficiency hypocalcemia was associated with elevation of serum PTH levels. Infusion of exogenous PTH induced a clearly detectable renal response in the presence of hypomagnesemia but the response was diminished when serum magnesium was elevated. In this patient it appears that hypomagnesemia suppressed parathyroid gland activity, leaving the renal action of PTH intact."}
{"id": "PMID:231068", "title": "Radioimmunoassay for antibodies in varicella-zoster virus serology.", "content": "The method of RIA for antibodies was employed with success in VZ virus serology. The method is suitable for testing VZ antibodies in the course of varicella or herpes zoster disease as well as for determining anamnestic titres. Its advantages are stability of antigen, objective reading of results and applicability to testing large serum sets.", "contents": "Radioimmunoassay for antibodies in varicella-zoster virus serology. The method of RIA for antibodies was employed with success in VZ virus serology. The method is suitable for testing VZ antibodies in the course of varicella or herpes zoster disease as well as for determining anamnestic titres. Its advantages are stability of antigen, objective reading of results and applicability to testing large serum sets."}
{"id": "PMID:231069", "title": "Haemagglutination-inhibiting and neutralizing antibodies to type 3 and 5 rhinoviruses in human sera and nasal washings.", "content": "Presence of antibodies to RV 3 and RV 5 was tested by HIT and NT in 60 human sera. Antibodies to RV 3 were detected in 23 sera by HIT in a titre range of 1:4--1:64 and in 19 sera by NT in a titre range of 1:4--1:256. Antibodies to RV 5 were detected in 31 sera by HIT in titres of 1:4--1:268 and 27 sera by NT in the same titre range. In a group of 22 persons with unequivocal serum antibodies nasal secretory antibodies were found in 11 subjects in titres of 1:4--1:32. In a group of 16 persons without detectable serum antibodies, presence of secretory antibodies (titre 1:4) was only found in four cases.", "contents": "Haemagglutination-inhibiting and neutralizing antibodies to type 3 and 5 rhinoviruses in human sera and nasal washings. Presence of antibodies to RV 3 and RV 5 was tested by HIT and NT in 60 human sera. Antibodies to RV 3 were detected in 23 sera by HIT in a titre range of 1:4--1:64 and in 19 sera by NT in a titre range of 1:4--1:256. Antibodies to RV 5 were detected in 31 sera by HIT in titres of 1:4--1:268 and 27 sera by NT in the same titre range. In a group of 22 persons with unequivocal serum antibodies nasal secretory antibodies were found in 11 subjects in titres of 1:4--1:32. In a group of 16 persons without detectable serum antibodies, presence of secretory antibodies (titre 1:4) was only found in four cases."}
{"id": "PMID:231065", "title": "Responses of anterior pituitary hormones to heat exposure.", "content": "To determine anterior pituitary response to mild hyperthermia, plasma GH, ACTH, PRL and TSH were measured every 10 min in five subjects exposed to hot air (120 min, 50 C, 20 mbar) in a climatic chamber. Mean rectal temperatures increases of 0,8 C and mean sweat losses of 760 g were observed. GH levels increased from 4.4 +/- 0.4 ng/ml to 22.0 +/- 7.0 ng/ml (mean +/- SE) and reached maximum 80 min after the beginning of heat exposure and then declined before the end of the heat stress. These peak levels varied widely with the individual, whereas no significant changes in ACTH, PRL and TSH levels were observed during the exposure period. These results suggest that the mechanisms regulating GH secretion are more sensitive to an acute heat exposure than those of the other pituitary hormones studied.", "contents": "Responses of anterior pituitary hormones to heat exposure. To determine anterior pituitary response to mild hyperthermia, plasma GH, ACTH, PRL and TSH were measured every 10 min in five subjects exposed to hot air (120 min, 50 C, 20 mbar) in a climatic chamber. Mean rectal temperatures increases of 0,8 C and mean sweat losses of 760 g were observed. GH levels increased from 4.4 +/- 0.4 ng/ml to 22.0 +/- 7.0 ng/ml (mean +/- SE) and reached maximum 80 min after the beginning of heat exposure and then declined before the end of the heat stress. These peak levels varied widely with the individual, whereas no significant changes in ACTH, PRL and TSH levels were observed during the exposure period. These results suggest that the mechanisms regulating GH secretion are more sensitive to an acute heat exposure than those of the other pituitary hormones studied."}
{"id": "PMID:231070", "title": "Enhancement of fluorescent antibody staining of viral antigens in formalin-fixed tissues by trypsin digestion.", "content": "The staining of viral antigens present in formalin-fixed, paraffin-embedded tissues by fluorescent antibodies is markedly enhanced by trypsin digestion. When the trypsin digestion method was used to detect viral antigens present in hamster brain following experimental infection with measles virus, the results were comparable to those obtained with acetone-fixed, freshly frozen tissues that had been sectioned with a cryostat. Measles antigens were readily identified in brain cells from a patient with subacute sclerosing panencephalitis and in lung and liver tissue from a patient with acute giant cell pneumonia, following preparation of the tissues for routine histologic examination. Viral antigens were detected in brain tissue that had been taken from patients with herpes simplex encephalitis and stored in paraffin for up to 15 years. Cells containing antigen could be precisely identified without loss of histologic detail by restaining the same tissue sections with hematoxylin and eosin.", "contents": "Enhancement of fluorescent antibody staining of viral antigens in formalin-fixed tissues by trypsin digestion. The staining of viral antigens present in formalin-fixed, paraffin-embedded tissues by fluorescent antibodies is markedly enhanced by trypsin digestion. When the trypsin digestion method was used to detect viral antigens present in hamster brain following experimental infection with measles virus, the results were comparable to those obtained with acetone-fixed, freshly frozen tissues that had been sectioned with a cryostat. Measles antigens were readily identified in brain cells from a patient with subacute sclerosing panencephalitis and in lung and liver tissue from a patient with acute giant cell pneumonia, following preparation of the tissues for routine histologic examination. Viral antigens were detected in brain tissue that had been taken from patients with herpes simplex encephalitis and stored in paraffin for up to 15 years. Cells containing antigen could be precisely identified without loss of histologic detail by restaining the same tissue sections with hematoxylin and eosin."}
{"id": "PMID:231072", "title": "Lack of susceptibility of marmosets to human non-A, non-B hepatitis.", "content": "Infectious sera from three humans with chronic non-A, non-B hepatitis, whose blood or serum had transmitted non-A, non-B hepatitis both to other humans and to experimentally inoculated chimpanzees, were inoculated into five marmosets. A sixth uninoculated marmoset served as a control. No elevations in levels of serum alanine aminotransferase or isocitric dehydrogenase occurred in serum samples obtained weekly from any of the marmosets during three months following inoculation. This study indicates that certain species of marmoset, which are susceptible to and provide well-documented animal models for hepatitis A and GB-agent hepatitis, do not appear to be susceptible to the agent(s) of human non-A, non-B hepatitis. In addition, this study suggests that the agent(s) of human non-A, non-B hepatitis and the GB agent are probably different.", "contents": "Lack of susceptibility of marmosets to human non-A, non-B hepatitis. Infectious sera from three humans with chronic non-A, non-B hepatitis, whose blood or serum had transmitted non-A, non-B hepatitis both to other humans and to experimentally inoculated chimpanzees, were inoculated into five marmosets. A sixth uninoculated marmoset served as a control. No elevations in levels of serum alanine aminotransferase or isocitric dehydrogenase occurred in serum samples obtained weekly from any of the marmosets during three months following inoculation. This study indicates that certain species of marmoset, which are susceptible to and provide well-documented animal models for hepatitis A and GB-agent hepatitis, do not appear to be susceptible to the agent(s) of human non-A, non-B hepatitis. In addition, this study suggests that the agent(s) of human non-A, non-B hepatitis and the GB agent are probably different."}
{"id": "PMID:231073", "title": "Phagocytosis and intracellular fate of Sporothrix schenckii.", "content": "Human polymorphonuclear leukocytes (PMNLs) phagocytized and killed yeast-phase cells of Sporothrix schenckii in vitro in the presence of 10% unheated serum. The combination of H2O2, KI, and human PMNL myeloperoxidase was lethal to yeast-phase S. schenckii. The results of this investigation suggest that PMNLs may play an important role in host resistance to infection with S. schenckii.", "contents": "Phagocytosis and intracellular fate of Sporothrix schenckii. Human polymorphonuclear leukocytes (PMNLs) phagocytized and killed yeast-phase cells of Sporothrix schenckii in vitro in the presence of 10% unheated serum. The combination of H2O2, KI, and human PMNL myeloperoxidase was lethal to yeast-phase S. schenckii. The results of this investigation suggest that PMNLs may play an important role in host resistance to infection with S. schenckii."}
{"id": "PMID:231074", "title": "[Arterial patterns in congenital deformities of the hand (author's transl)].", "content": "Etiology of congenital deformities of the hand is still unknown in most cases. But anomalous development of arteries has been suspected to play a role in faulty development of the hands. Senior (1926) and Singer (1933) have reported arterial anomalies in the developmental stage of these vessels. Between 1968 and 1978, 367 patients with 453 congenital deformities of the hand visited the hand service of Kyoto University Hospital. These hand anomalies were classified according to Swanson's classification. Angiography was performed on 74 hands of 70 patients in this series, and attempts were made to correlate these with the types of the deformities. From the standpoint of embryological development of arteries, it is concluded that failure of formation of parts (arrest of development), failure of differentiation (separation) of parts and duplication are generated in the same stage from 48 days postovulatory (18 mm embryo), overgrowth (gigantism) of the hand and congenital constriction band syndrome are generated after 52 days postovulatory (23 mm embryo). Generalized skeletal anomalies are considered to be generated in the various developmental stages depending on the each malformed hands. Developmental stage of malformed hands with generalized skeletal abnormalities is discussed with special reference to the embryological development of other anomalies.", "contents": "[Arterial patterns in congenital deformities of the hand (author's transl)]. Etiology of congenital deformities of the hand is still unknown in most cases. But anomalous development of arteries has been suspected to play a role in faulty development of the hands. Senior (1926) and Singer (1933) have reported arterial anomalies in the developmental stage of these vessels. Between 1968 and 1978, 367 patients with 453 congenital deformities of the hand visited the hand service of Kyoto University Hospital. These hand anomalies were classified according to Swanson's classification. Angiography was performed on 74 hands of 70 patients in this series, and attempts were made to correlate these with the types of the deformities. From the standpoint of embryological development of arteries, it is concluded that failure of formation of parts (arrest of development), failure of differentiation (separation) of parts and duplication are generated in the same stage from 48 days postovulatory (18 mm embryo), overgrowth (gigantism) of the hand and congenital constriction band syndrome are generated after 52 days postovulatory (23 mm embryo). Generalized skeletal anomalies are considered to be generated in the various developmental stages depending on the each malformed hands. Developmental stage of malformed hands with generalized skeletal abnormalities is discussed with special reference to the embryological development of other anomalies."}
{"id": "PMID:231077", "title": "Erythrocyte membrane enzyme abnormalities in two hereditary disorders of muscle.", "content": "Enzymatic properties of erythrocyte membranes in Duchenne muscular dystrophy (DMD) and malignant hyperthermia (MH), two genetically determined abnormalities of skeletal muscle, were examined. Acetylcholinesterase (AChE) and ATPase activities were chosen for investigation since alterations in these enzymes have been demonstrated in animal models of dystrophy. A significant decrease in Na+,K+-ATPase activity was noted in DMD patients and a number of possible DMD carriers, suggesting that this enzyme may provide a useful marker of the carrier state in carriers not exhibiting an elevation in plasma creatine phosphokinase activity. No abnormalities in AChE were demonstrable in any of our DMD patients, indicating that human dystrophy is biochemically distinct from certain animal models of dystrophy (e.g., dystrophic mice) where erythrocyte AChE is decreased. In contrast, evidence was found in two known MH carriers, who had normal erythrocyte ATPase activities, for the presence of an altered membrane AChE characterized by an increase in substrate affinity and a large decrease in maximal hydrolytic rate. While the exact relevance of this membrane defect, if any, to the pathogenesis of MH remains to be seen, the presence of this modified enzyme may serve to identify those individuals in a family where a positive history of MH exists who are at risk of developing a hyperthermic crisis during anesthesia.", "contents": "Erythrocyte membrane enzyme abnormalities in two hereditary disorders of muscle. Enzymatic properties of erythrocyte membranes in Duchenne muscular dystrophy (DMD) and malignant hyperthermia (MH), two genetically determined abnormalities of skeletal muscle, were examined. Acetylcholinesterase (AChE) and ATPase activities were chosen for investigation since alterations in these enzymes have been demonstrated in animal models of dystrophy. A significant decrease in Na+,K+-ATPase activity was noted in DMD patients and a number of possible DMD carriers, suggesting that this enzyme may provide a useful marker of the carrier state in carriers not exhibiting an elevation in plasma creatine phosphokinase activity. No abnormalities in AChE were demonstrable in any of our DMD patients, indicating that human dystrophy is biochemically distinct from certain animal models of dystrophy (e.g., dystrophic mice) where erythrocyte AChE is decreased. In contrast, evidence was found in two known MH carriers, who had normal erythrocyte ATPase activities, for the presence of an altered membrane AChE characterized by an increase in substrate affinity and a large decrease in maximal hydrolytic rate. While the exact relevance of this membrane defect, if any, to the pathogenesis of MH remains to be seen, the presence of this modified enzyme may serve to identify those individuals in a family where a positive history of MH exists who are at risk of developing a hyperthermic crisis during anesthesia."}
{"id": "PMID:231079", "title": "Red cell deformability: physiological, clinical and pharmacological aspects.", "content": "Twenty five thousand billions of red cells circulate through 300 miles of capillary network. The red cell diameter is 7 to 8 microns and the capillary diameter 3 to 5 micron. Red cells deformability is therefore an essential condition for survival. It is impaired in a certain number of clinical conditions. A French task force, covering 40 University Hospitals, is presently investigating the clinical implications of red cell filterability, and its possible therapeutical consequences.", "contents": "Red cell deformability: physiological, clinical and pharmacological aspects. Twenty five thousand billions of red cells circulate through 300 miles of capillary network. The red cell diameter is 7 to 8 microns and the capillary diameter 3 to 5 micron. Red cells deformability is therefore an essential condition for survival. It is impaired in a certain number of clinical conditions. A French task force, covering 40 University Hospitals, is presently investigating the clinical implications of red cell filterability, and its possible therapeutical consequences."}
{"id": "PMID:231084", "title": "Specificity of attachment of certain enterobacteriaceae to mammalian cells.", "content": "The specificity of adherence of various Enterobacteriaceae to different mammalian cells was studied in vitro. 3H-Labelled organisms of the same species isolated from various clinical sources differed significantly in their abilities to adhere to the same mammalian cells. Bacteria frequently adhered better to cells derived from sites other than those analogous to their original source. Bacteria did not display consistently 'high' or 'low' attachment to a variety of human and tissue-cultured cells and little selective adherence was demonstrable.", "contents": "Specificity of attachment of certain enterobacteriaceae to mammalian cells. The specificity of adherence of various Enterobacteriaceae to different mammalian cells was studied in vitro. 3H-Labelled organisms of the same species isolated from various clinical sources differed significantly in their abilities to adhere to the same mammalian cells. Bacteria frequently adhered better to cells derived from sites other than those analogous to their original source. Bacteria did not display consistently 'high' or 'low' attachment to a variety of human and tissue-cultured cells and little selective adherence was demonstrable."}
{"id": "PMID:231081", "title": "Effects of thyroxine treatment on the hepatic plasma membrane ATPase activity in rats.", "content": "The effects of T4 and T3 upon ATPase activity of plasma membrane preparations produced by different methods has been studied. Media without Na+ or K+ was used to identify Mg++ activated ATPase, and media containing 100-120 mM Na+ and 20-30 mM K+ in addition to Mg++ was used to identify the augmented activity of Na-K ATPase. We also utilized media containing Na+, K+, and Mg++ in the presence and absence of ouabain to identify the Na+-K+ activation. We found no effect of doses of thyroxine in the physiologic range upon the Na+-K+ ATPase activity. A dose-response study indicated that high doses of T4 may stimulate Mg++ activated ATPase. In the P2 preparation of the Touster method we found minimally enhanced Na+-K+ ATPase activity. The quantity of T4 needed to cause such enhancement is approximately 50 times the physiologic replacement dose needed to restore thyroidectomized animals to a euthyroid state. We conclude that thyroid hormones do not stimulate Na+-K+ ATPase of plasma membranes when administered in a physiologic quantity, but may enhance Mg++ atpase activity when administered in a pharmacologic or toxic quantity.", "contents": "Effects of thyroxine treatment on the hepatic plasma membrane ATPase activity in rats. The effects of T4 and T3 upon ATPase activity of plasma membrane preparations produced by different methods has been studied. Media without Na+ or K+ was used to identify Mg++ activated ATPase, and media containing 100-120 mM Na+ and 20-30 mM K+ in addition to Mg++ was used to identify the augmented activity of Na-K ATPase. We also utilized media containing Na+, K+, and Mg++ in the presence and absence of ouabain to identify the Na+-K+ activation. We found no effect of doses of thyroxine in the physiologic range upon the Na+-K+ ATPase activity. A dose-response study indicated that high doses of T4 may stimulate Mg++ activated ATPase. In the P2 preparation of the Touster method we found minimally enhanced Na+-K+ ATPase activity. The quantity of T4 needed to cause such enhancement is approximately 50 times the physiologic replacement dose needed to restore thyroidectomized animals to a euthyroid state. We conclude that thyroid hormones do not stimulate Na+-K+ ATPase of plasma membranes when administered in a physiologic quantity, but may enhance Mg++ atpase activity when administered in a pharmacologic or toxic quantity."}
{"id": "PMID:231085", "title": "Inhibition of the replication of parvovirus X14 by 5-iodo-2'-deoxyuridine pre-treatment of cell cultures.", "content": "Pre-treatment of rat embryo cell cultures with 5-iodo-2'-deoxyuridine (IdUrd) inhibits the replication of parvovirus X14. Reduced yields of haemagglutinating and infectious particles were observed. Adsorption of virus to cells was not affected, but both virus protein and DNA synthesis were inhibited. Fewer cells were capable of supporting protein or antigen synthesis as determined by immunofluorescence. Virus-specific DNA was detected in IdUrd pre-treated cells, but the amount synthesized was considerably less than that from control cultures. Cellular DNA synthesis was also inhibited in IdUrd pre-treated cells. Therefore, the replication of parvoviruses appears dependent upon host cell factors involved in cellular DNA synthesis.", "contents": "Inhibition of the replication of parvovirus X14 by 5-iodo-2'-deoxyuridine pre-treatment of cell cultures. Pre-treatment of rat embryo cell cultures with 5-iodo-2'-deoxyuridine (IdUrd) inhibits the replication of parvovirus X14. Reduced yields of haemagglutinating and infectious particles were observed. Adsorption of virus to cells was not affected, but both virus protein and DNA synthesis were inhibited. Fewer cells were capable of supporting protein or antigen synthesis as determined by immunofluorescence. Virus-specific DNA was detected in IdUrd pre-treated cells, but the amount synthesized was considerably less than that from control cultures. Cellular DNA synthesis was also inhibited in IdUrd pre-treated cells. Therefore, the replication of parvoviruses appears dependent upon host cell factors involved in cellular DNA synthesis."}
{"id": "PMID:231086", "title": "A solid-phase system (SPACE) for the detection and quantification of rotavirus in faeces.", "content": "This report describes the development of a solid-phase haemadsorption system using chromic chloride-linked, antibody coated erythrocytes. It is proposed to call this technique solid phase aggregation of coupled erythrocytes (SPACE). The system is suitable for the detection of virus antigens, such as from rotavirus infections, which are present in 'dirty' or 'mixed' preparations such as faeces, urine or exudates. The test uses microtitre U-form plates coated with specific antivirus antibody; faecal suspensions are added and virus or antigen allowed to adsorb. The plates are then washed and adsorbed antigens are detected by the addition of virus-specific IgG-coated erythrocytes. The resultant settling pattern is read in the same manner as a conventional haemagglutination test. The system is compared with electron microscopy and fluorescent antibody techniques.", "contents": "A solid-phase system (SPACE) for the detection and quantification of rotavirus in faeces. This report describes the development of a solid-phase haemadsorption system using chromic chloride-linked, antibody coated erythrocytes. It is proposed to call this technique solid phase aggregation of coupled erythrocytes (SPACE). The system is suitable for the detection of virus antigens, such as from rotavirus infections, which are present in 'dirty' or 'mixed' preparations such as faeces, urine or exudates. The test uses microtitre U-form plates coated with specific antivirus antibody; faecal suspensions are added and virus or antigen allowed to adsorb. The plates are then washed and adsorbed antigens are detected by the addition of virus-specific IgG-coated erythrocytes. The resultant settling pattern is read in the same manner as a conventional haemagglutination test. The system is compared with electron microscopy and fluorescent antibody techniques."}
{"id": "PMID:231082", "title": "The mitochondrial activation of silicate and its role in silicosis, black lung disease and lung cancer.", "content": "Silicate substitutes for phosphate in the transitory uncoupling of rat liver mitochondria induced by hydrazine when beta-hydroxy-butyrate is the substrate. Uncoupling is blocked by rutamycin. Just as in the case when phosphate is combined with hydrazine, ATP, ADP, PPi, and Mg++ protect against hydrazine when silicate is combined with hydrazine. A high level of ADP in the absence of added phosphate, but in the presence of silicate, induces a pseudo state three of the mitochondria. Silicate, like sulfate and arsenate which have been reported previously, is activated by the enzymes which mediate oxidative phosphorylation. These results serve to explain a role for silicate in silicosis, black lung disease, and cancer. In addition, since there is suggestive evidence in the literature that lung tissue solubilizes asbestos fibers, these results not only expand the confluence between oxidative phosphorylation and chemical carcinogenesis but are correlated with the synergistic carcinogenicity of asbestos and smoking observed by epidemiologists.", "contents": "The mitochondrial activation of silicate and its role in silicosis, black lung disease and lung cancer. Silicate substitutes for phosphate in the transitory uncoupling of rat liver mitochondria induced by hydrazine when beta-hydroxy-butyrate is the substrate. Uncoupling is blocked by rutamycin. Just as in the case when phosphate is combined with hydrazine, ATP, ADP, PPi, and Mg++ protect against hydrazine when silicate is combined with hydrazine. A high level of ADP in the absence of added phosphate, but in the presence of silicate, induces a pseudo state three of the mitochondria. Silicate, like sulfate and arsenate which have been reported previously, is activated by the enzymes which mediate oxidative phosphorylation. These results serve to explain a role for silicate in silicosis, black lung disease, and cancer. In addition, since there is suggestive evidence in the literature that lung tissue solubilizes asbestos fibers, these results not only expand the confluence between oxidative phosphorylation and chemical carcinogenesis but are correlated with the synergistic carcinogenicity of asbestos and smoking observed by epidemiologists."}
{"id": "PMID:231087", "title": "Integration of herpes simplex virus type 1 DNA into the DNA of growth-arrested BHK-21 cells.", "content": "The ability of HSV-1 DNA to become associated with host cell DNA in an alkaline-stable form has been demonstrated following infection of a ts baby hamster kidney growth mutant (ts BTN-1), at the non-permissive temperature (39.5 depgrees C). After 8 h pre-incubation at 39.5 degrees C, ts BTN-1 cells infected at this temperature using m.o.i. ranging from 0.5 to 200 p.f.u./cell fail to replicate virus DNA even though transport of input virus genomes to the nucleus is the same at both permissive and non-permissive temperatures. Virions containing 3H-labelled DNA were used to infect ts BTN-1 cells at 39.5 degrees C, and the total cellular DNA isolated from these cells was resolved into host and virus material by repeated CsCl equilibrium gradient centrifugation. A significant amount of the input radioactivity was found as a distinct band in the host region in both neutral and alkaline CsCl gradients, strongly suggesting a covalent association between host and virus DNAs. Evidence for this association was strengthened by demonstrating that radioactive material (virus DNA) banding in the host region of CsCl gradients could be driven towards the density expected for virus DNA following degradation of the putative hybrid molecules by shearing.", "contents": "Integration of herpes simplex virus type 1 DNA into the DNA of growth-arrested BHK-21 cells. The ability of HSV-1 DNA to become associated with host cell DNA in an alkaline-stable form has been demonstrated following infection of a ts baby hamster kidney growth mutant (ts BTN-1), at the non-permissive temperature (39.5 depgrees C). After 8 h pre-incubation at 39.5 degrees C, ts BTN-1 cells infected at this temperature using m.o.i. ranging from 0.5 to 200 p.f.u./cell fail to replicate virus DNA even though transport of input virus genomes to the nucleus is the same at both permissive and non-permissive temperatures. Virions containing 3H-labelled DNA were used to infect ts BTN-1 cells at 39.5 degrees C, and the total cellular DNA isolated from these cells was resolved into host and virus material by repeated CsCl equilibrium gradient centrifugation. A significant amount of the input radioactivity was found as a distinct band in the host region in both neutral and alkaline CsCl gradients, strongly suggesting a covalent association between host and virus DNAs. Evidence for this association was strengthened by demonstrating that radioactive material (virus DNA) banding in the host region of CsCl gradients could be driven towards the density expected for virus DNA following degradation of the putative hybrid molecules by shearing."}
{"id": "PMID:231083", "title": "Analysis of adipose tissue and serum from PBB (polybrominated biphenyl)-exposed workers.", "content": "In the course of clinical examinations of individuals exposed to PBB (polybrominated biphenyl(s) in Michigan, employees of the chemical company which manufactured PBB also were examined. Analysis of serum and adipose tissue from these workers revealed quantitative and qualitative differences, compared with farm residents exposed to PBB. Serum and fat concentrations of PBB were higher among chemical workers, and the concentrations of PBB homologs were also higher, attributable to different intensity, route (skin, inhalation, direct ingestion vs. ingestion of animal foodstuffs), and composition (unchanged vs. animal-mediated material) of exposure in chemical workers vs. farmers. The unusual nature of occupational exposure was further evident in measurement of serum and fat DDE and identification of serum tetrabromobenzene (TBB). DDE concentrations were higher among employees than among farmers, consistent with the workers' earlier occupational exposure to DDT, which had been produced by the company. Serum TBB was not explicable by direct exposure to the chemical, but has been ascribed to exposure to hexabromobenzene, which was shown to give tetrabromobenzene as a metabolite in the rat.", "contents": "Analysis of adipose tissue and serum from PBB (polybrominated biphenyl)-exposed workers. In the course of clinical examinations of individuals exposed to PBB (polybrominated biphenyl(s) in Michigan, employees of the chemical company which manufactured PBB also were examined. Analysis of serum and adipose tissue from these workers revealed quantitative and qualitative differences, compared with farm residents exposed to PBB. Serum and fat concentrations of PBB were higher among chemical workers, and the concentrations of PBB homologs were also higher, attributable to different intensity, route (skin, inhalation, direct ingestion vs. ingestion of animal foodstuffs), and composition (unchanged vs. animal-mediated material) of exposure in chemical workers vs. farmers. The unusual nature of occupational exposure was further evident in measurement of serum and fat DDE and identification of serum tetrabromobenzene (TBB). DDE concentrations were higher among employees than among farmers, consistent with the workers' earlier occupational exposure to DDT, which had been produced by the company. Serum TBB was not explicable by direct exposure to the chemical, but has been ascribed to exposure to hexabromobenzene, which was shown to give tetrabromobenzene as a metabolite in the rat."}
{"id": "PMID:231088", "title": "In vivo and in vitro phosphorylation of murine mammary tumour virus proteins.", "content": "A comparative study of in vitro and in vivo phosphorylation of murine mammary tumour virus, a type Brna virus, is reported. The protein kinase activity associated with murine mammary tumour virus catalysed the in vitro phosphorylation of endogenous virus polypeptides. This kinase activity required a divalent metal cation, a non-ionic detergent, and was stimulated in the presence of dithiothreitol. Exogenous cyclic AMP was not required. The 32P-labelled products of the in vitro reaction were completely sensitive to pronase digestion and the phosphate was attached mainly by phosphomonoester linkage to serine residues. As determined by SDS-polyacrylamide gel electrophoresis, heterogeneous labelling of major and minor virus polypeptides was observed under in vitro conditions. In contrast, the in vivo labelling of type B virus produced by a continuous cell line (MuMT-73), established from pooled mammary adenocarcinomas of Balb/cfC3H mice, demonstrated specific phosphoproteins associated with murine mammary tumour virus. The major phosphorylated proteins were found to have mol. wt. of 18 000 and 12 000 (p18 and p12) after isolation by molecular sieving chromatography and analysis by gel electrophoresis.", "contents": "In vivo and in vitro phosphorylation of murine mammary tumour virus proteins. A comparative study of in vitro and in vivo phosphorylation of murine mammary tumour virus, a type Brna virus, is reported. The protein kinase activity associated with murine mammary tumour virus catalysed the in vitro phosphorylation of endogenous virus polypeptides. This kinase activity required a divalent metal cation, a non-ionic detergent, and was stimulated in the presence of dithiothreitol. Exogenous cyclic AMP was not required. The 32P-labelled products of the in vitro reaction were completely sensitive to pronase digestion and the phosphate was attached mainly by phosphomonoester linkage to serine residues. As determined by SDS-polyacrylamide gel electrophoresis, heterogeneous labelling of major and minor virus polypeptides was observed under in vitro conditions. In contrast, the in vivo labelling of type B virus produced by a continuous cell line (MuMT-73), established from pooled mammary adenocarcinomas of Balb/cfC3H mice, demonstrated specific phosphoproteins associated with murine mammary tumour virus. The major phosphorylated proteins were found to have mol. wt. of 18 000 and 12 000 (p18 and p12) after isolation by molecular sieving chromatography and analysis by gel electrophoresis."}
{"id": "PMID:231090", "title": "Host-cell response to herpes virus infection in central and peripheral nervous tissue in vitro.", "content": "In an organotypic nerve cell culture system, all cells in both the central and the peripheral nervous system (CNS, PNS) components supported replication of herpes simplex virus types 1 and 2 (HSV 1, HSV 2). In HSV 1 infection, cellular response was particularly characterized by the formation of small syncytia (which involved neurons) and by the presence of bundles of interwoven fine filaments within the nuclei of infected cells. In HSV 2 infection, groups of parallel tubules characteristically formed in the nuclei of infected cells. All cells in the CNS or PNS succumbed to virus infection, some within 24 h (e.g. oligodendrocytes) and others after 48 h (e.g. neurons), with the exception of astrocytes. Although among the first cells to develop virus nucleocapsids in their nuclei, astrocytes became swollen and filled with increased numbers of bundles of glial filaments within 24 h after infection; by 48 h the actual number of astrocytes was increased by as much as three- to fourfold over the number in controls. The results suggest that astrocytes may have a unique mechanism which modifies virus infection and the cells not only survive, but can also become reactive.", "contents": "Host-cell response to herpes virus infection in central and peripheral nervous tissue in vitro. In an organotypic nerve cell culture system, all cells in both the central and the peripheral nervous system (CNS, PNS) components supported replication of herpes simplex virus types 1 and 2 (HSV 1, HSV 2). In HSV 1 infection, cellular response was particularly characterized by the formation of small syncytia (which involved neurons) and by the presence of bundles of interwoven fine filaments within the nuclei of infected cells. In HSV 2 infection, groups of parallel tubules characteristically formed in the nuclei of infected cells. All cells in the CNS or PNS succumbed to virus infection, some within 24 h (e.g. oligodendrocytes) and others after 48 h (e.g. neurons), with the exception of astrocytes. Although among the first cells to develop virus nucleocapsids in their nuclei, astrocytes became swollen and filled with increased numbers of bundles of glial filaments within 24 h after infection; by 48 h the actual number of astrocytes was increased by as much as three- to fourfold over the number in controls. The results suggest that astrocytes may have a unique mechanism which modifies virus infection and the cells not only survive, but can also become reactive."}
{"id": "PMID:231091", "title": "Inactivation by u.v.-irradiation of interfering herpes simplex virus particles: interference requires a functional genome.", "content": "The sensitivity of interfering herpes simplex virus (HSV) particles to u.v.-irradiation was studied in a virus stock of HSV-1 strain ANG that contained an excess of interfering over infectious particles. Following u.v.-irradiation, samples of this virus stock were assayed for their plaque-forming capacity and their capacity to interfere with the replication of unirradiated standard virus. Depending on the assay conditions, interfering particles appeared to be less, equally, or more sensitive to u.v. light than infectious particles. It is concluded that interference is a gene function of interfering particles rather than being exerted directly by structural constituents of these particles.", "contents": "Inactivation by u.v.-irradiation of interfering herpes simplex virus particles: interference requires a functional genome. The sensitivity of interfering herpes simplex virus (HSV) particles to u.v.-irradiation was studied in a virus stock of HSV-1 strain ANG that contained an excess of interfering over infectious particles. Following u.v.-irradiation, samples of this virus stock were assayed for their plaque-forming capacity and their capacity to interfere with the replication of unirradiated standard virus. Depending on the assay conditions, interfering particles appeared to be less, equally, or more sensitive to u.v. light than infectious particles. It is concluded that interference is a gene function of interfering particles rather than being exerted directly by structural constituents of these particles."}
{"id": "PMID:231092", "title": "Transformation and T antigen induction by linearized BK virus DNA.", "content": "Linearized unit length DNA obtained after cleavage of the supercoiled DNA of the human papovavirus BKV by PstI (.031) induced transformation and T antigen less efficiently than DNA cleaved by EcoRI (0.0), BamHI (0.98), KpnI (0.90) or HhaI (0.73). BKV DNA cleaved by XbaI (0.27 and 0.95) did not induce T antigen.", "contents": "Transformation and T antigen induction by linearized BK virus DNA. Linearized unit length DNA obtained after cleavage of the supercoiled DNA of the human papovavirus BKV by PstI (.031) induced transformation and T antigen less efficiently than DNA cleaved by EcoRI (0.0), BamHI (0.98), KpnI (0.90) or HhaI (0.73). BKV DNA cleaved by XbaI (0.27 and 0.95) did not induce T antigen."}
{"id": "PMID:231093", "title": "Blocking of acid-fixed nuclear binding of Epstein-Barr virus nuclear antigen (EBNA) by different DNA species.", "content": "Treatment of Epstein-Barr virus-determined nuclear antigen (EBNA) with DNA resulted in blocking of its ability to convert acid-fixed EBNA-negative cell nuclei to an EBNA-positive form. Epstein-Barr virus (EBV) DNA, herpes simplex virus type 2 (HSV-2) DNA and DNA isolated from three lymphoblastoid cell lines differed in their potency to block this reaction. EBV DNA was found to be about three times more effective than cellular DNAs in abolishing the ability of DNA-cellulose-purified EBNA to convert acid-fixed nuclei to the EBNA-positive form; the effect of HSV-2 DNA was of intermediate character. No difference was found between the blocking potency of DNAs isolated from EBV-genome-negative Ramos cells and EBV-genome-positive Raji and P3HR-1 cells.", "contents": "Blocking of acid-fixed nuclear binding of Epstein-Barr virus nuclear antigen (EBNA) by different DNA species. Treatment of Epstein-Barr virus-determined nuclear antigen (EBNA) with DNA resulted in blocking of its ability to convert acid-fixed EBNA-negative cell nuclei to an EBNA-positive form. Epstein-Barr virus (EBV) DNA, herpes simplex virus type 2 (HSV-2) DNA and DNA isolated from three lymphoblastoid cell lines differed in their potency to block this reaction. EBV DNA was found to be about three times more effective than cellular DNAs in abolishing the ability of DNA-cellulose-purified EBNA to convert acid-fixed nuclei to the EBNA-positive form; the effect of HSV-2 DNA was of intermediate character. No difference was found between the blocking potency of DNAs isolated from EBV-genome-negative Ramos cells and EBV-genome-positive Raji and P3HR-1 cells."}
{"id": "PMID:231094", "title": "Cell-mediated cytotoxicity following influenza infection and vaccination in humans.", "content": "Cell-mediated cytotoxic activity in circulating mononuclear cells from 31 volunteers challenged with live influenza A/Victoria virus, and 22 volunteers vaccinated with inactivated influenza vaccine, was examined employing target cells infected with several viruses by means of a 51Cr release assay. Effectors from infected volunteers, and from volunteers who manifested four-fold rises in serum HAI antibody after vaccination, demonstrated significantly elevated levels of cytotoxicity against targets infected with the homologous virus. Elevated cytotoxicity was seen by days 3 and 4 after challenge or vaccination and returned to baseline levels by day 9 to 10. In infected volunteers, cytotoxic activity was broadly directed, rising against targets infected with an antigenically distinct virus within the same influenza type (A), against targets infected with a serologically unrelated virus of a different influenza type (B), and also against cells infected with Newcastle disease virus, a paramyxovirus from another species. However, elevated levels of cytotoxicity were not observed when targets infected with herpes simplex virus, a member of an entirely different virus group, or when uninfected target cells were employed. In vaccinated volunteers, the rise in cytotoxicity was more restricted than after infection, since elevated cytotoxic activity was seen only against cells infected with the homologous virus and not against inflenza B-infected cells. Fractionation of mononuclear cell populations indicated that effector cell activity is associated with T-cell depleted fractions and can only partially be reduced by depletion of adherent cells. The rapid development, short duration, and broadly directed specificity of this cytotoxic response suggest that it may be involved in early events following acute influenza infection in humans.", "contents": "Cell-mediated cytotoxicity following influenza infection and vaccination in humans. Cell-mediated cytotoxic activity in circulating mononuclear cells from 31 volunteers challenged with live influenza A/Victoria virus, and 22 volunteers vaccinated with inactivated influenza vaccine, was examined employing target cells infected with several viruses by means of a 51Cr release assay. Effectors from infected volunteers, and from volunteers who manifested four-fold rises in serum HAI antibody after vaccination, demonstrated significantly elevated levels of cytotoxicity against targets infected with the homologous virus. Elevated cytotoxicity was seen by days 3 and 4 after challenge or vaccination and returned to baseline levels by day 9 to 10. In infected volunteers, cytotoxic activity was broadly directed, rising against targets infected with an antigenically distinct virus within the same influenza type (A), against targets infected with a serologically unrelated virus of a different influenza type (B), and also against cells infected with Newcastle disease virus, a paramyxovirus from another species. However, elevated levels of cytotoxicity were not observed when targets infected with herpes simplex virus, a member of an entirely different virus group, or when uninfected target cells were employed. In vaccinated volunteers, the rise in cytotoxicity was more restricted than after infection, since elevated cytotoxic activity was seen only against cells infected with the homologous virus and not against inflenza B-infected cells. Fractionation of mononuclear cell populations indicated that effector cell activity is associated with T-cell depleted fractions and can only partially be reduced by depletion of adherent cells. The rapid development, short duration, and broadly directed specificity of this cytotoxic response suggest that it may be involved in early events following acute influenza infection in humans."}
{"id": "PMID:231095", "title": "Decreased cell-mediated cytotoxicity against virus-infected cells in systemic lupus erythematosus.", "content": "Cell-mediated cytotoxicity, directed against virus-infected tissue culture cells, was studied with peripheral blood mononuclear cells from 11 patients with systemic lupus erythematosus (SLE) and 12 matched, normal subjects in a 51Cr release assay. Baseline (preimmunization) levels of cytotoxicity against target cells infected with influenza A/Victoria, influenza B/Hong Kong, Newcastle disease virus, and herpes simplex virus were significantly decreased in patients with SLE compared to normal subjects (P less than 0.001), although serum antibody levels to the respective viruses were similar in both groups. After intramuscular administration of inactivated influenza A/Victoria vaccine, SLE patients failed to generate elevated levels of cytotoxicity against A/Victoria-infected cells, in contrast to normal subjects. SLE patients responded with levels of serum hemagglutination-inhibition antibody which were similar to those of normal subjects. Thus, SLE patients manifest decreased cell-mediated cytotoxicity against virus-infected target cells, although humoral antibody responses appeared to be intact. Studies of SLE patients with influenza may help to define the role of cell-mediated immunity in the pathogenesis of certain viral infections.", "contents": "Decreased cell-mediated cytotoxicity against virus-infected cells in systemic lupus erythematosus. Cell-mediated cytotoxicity, directed against virus-infected tissue culture cells, was studied with peripheral blood mononuclear cells from 11 patients with systemic lupus erythematosus (SLE) and 12 matched, normal subjects in a 51Cr release assay. Baseline (preimmunization) levels of cytotoxicity against target cells infected with influenza A/Victoria, influenza B/Hong Kong, Newcastle disease virus, and herpes simplex virus were significantly decreased in patients with SLE compared to normal subjects (P less than 0.001), although serum antibody levels to the respective viruses were similar in both groups. After intramuscular administration of inactivated influenza A/Victoria vaccine, SLE patients failed to generate elevated levels of cytotoxicity against A/Victoria-infected cells, in contrast to normal subjects. SLE patients responded with levels of serum hemagglutination-inhibition antibody which were similar to those of normal subjects. Thus, SLE patients manifest decreased cell-mediated cytotoxicity against virus-infected target cells, although humoral antibody responses appeared to be intact. Studies of SLE patients with influenza may help to define the role of cell-mediated immunity in the pathogenesis of certain viral infections."}
{"id": "PMID:231096", "title": "A new principle for the detection of specific IgM antibodies applied in an ELISA for hepatitis A.", "content": "A new test principle for the detection of specific IgM-class antibodies was developed and applied in an Enzyme-Linked Immuno Sorbent Assay (ELISA) for the detection of hepatitis A IgM antibodies. A solid phase coated with anti-IgM was incubated successively with serum sample, specific antigen, and enzyme-labeled F (ab')2 fragments from IgG antibodies against the antigen and enzyme substrate. F(ab')2 fragments were used to avoid interference with rheumatoid factor. Specificity and sensitivity are very high. This test principle appears generally applicable in the diagnosis of infectious and parasitic diseases by testing only one serum sample.", "contents": "A new principle for the detection of specific IgM antibodies applied in an ELISA for hepatitis A. A new test principle for the detection of specific IgM-class antibodies was developed and applied in an Enzyme-Linked Immuno Sorbent Assay (ELISA) for the detection of hepatitis A IgM antibodies. A solid phase coated with anti-IgM was incubated successively with serum sample, specific antigen, and enzyme-labeled F (ab')2 fragments from IgG antibodies against the antigen and enzyme substrate. F(ab')2 fragments were used to avoid interference with rheumatoid factor. Specificity and sensitivity are very high. This test principle appears generally applicable in the diagnosis of infectious and parasitic diseases by testing only one serum sample."}
{"id": "PMID:231097", "title": "Effects of continuous lighting or continuous darkness on large granulated vesicles in sympathetic nerve fibers of the mouse pineal--quantitative electron microscopic observations.", "content": "The influence of continuous light or darkness on the large granulated vesicles in sympathetic nerve fibers of the mouse pineal was investigated by means of quantitative electron microscopic techniques. Continuous illumination at about 20 lux caused the disappearance of the diurnal rhythm in the number of the large granulated vesicles, followed by an accumulation of these vesicles. The diurnal rhythm of the large granulated vesicles was abolished in mice kept in continuous darkness for 7 days. These results suggest that the diurnal variation of the large granulated vesicles may be controlled directly by environmental light. Based on these findings, the relationships between small and large granulated vesicles were discussed.", "contents": "Effects of continuous lighting or continuous darkness on large granulated vesicles in sympathetic nerve fibers of the mouse pineal--quantitative electron microscopic observations. The influence of continuous light or darkness on the large granulated vesicles in sympathetic nerve fibers of the mouse pineal was investigated by means of quantitative electron microscopic techniques. Continuous illumination at about 20 lux caused the disappearance of the diurnal rhythm in the number of the large granulated vesicles, followed by an accumulation of these vesicles. The diurnal rhythm of the large granulated vesicles was abolished in mice kept in continuous darkness for 7 days. These results suggest that the diurnal variation of the large granulated vesicles may be controlled directly by environmental light. Based on these findings, the relationships between small and large granulated vesicles were discussed."}
{"id": "PMID:231098", "title": "Distribution of herpes simplex virus in acute necrotising encephalitis.", "content": "A 49-yr-old female developed a rapidly progressive neurological illness. The gross, light microscopic and electron-microscopic examination of the brain revealed all of the characteristic features of acute necrotising encephalitis with predominant involvement of the left limbic system. The distribution of herpes simplex virus suggests that the olfactory apparatus is the route of infection.", "contents": "Distribution of herpes simplex virus in acute necrotising encephalitis. A 49-yr-old female developed a rapidly progressive neurological illness. The gross, light microscopic and electron-microscopic examination of the brain revealed all of the characteristic features of acute necrotising encephalitis with predominant involvement of the left limbic system. The distribution of herpes simplex virus suggests that the olfactory apparatus is the route of infection."}
{"id": "PMID:231099", "title": "A comparison of the inhibitory effects of disodium pyrophosphate and disodium ethane-hydroxy-1, 1-diphosphonate on simple calcergy.", "content": "Both disodium pyrophosphate and disodium ethane-hydroxy-1, 1-diphosphate inhibit the reaction of simple calcergy induced in the mouse by lead acetate. The pyrophosphate is effective only by a direct interaction with the lead salt and the disphosphonate is effective only before the occurrence of histochemically demonstrable calcification.", "contents": "A comparison of the inhibitory effects of disodium pyrophosphate and disodium ethane-hydroxy-1, 1-diphosphonate on simple calcergy. Both disodium pyrophosphate and disodium ethane-hydroxy-1, 1-diphosphate inhibit the reaction of simple calcergy induced in the mouse by lead acetate. The pyrophosphate is effective only by a direct interaction with the lead salt and the disphosphonate is effective only before the occurrence of histochemically demonstrable calcification."}
{"id": "PMID:231100", "title": "Drinking behaviour in rats treated with isoprenaline, angiotensin II or angiotensin antagonists.", "content": "1. Isoprenaline hydrochloride injected subcutaneously in rats given a choice test of 1.8% NaCl and water, first induced saline intake which started immediately and was almost concluded in 15 min, followed by a copious water intake. When either saline or water were given in a separate test, saline intake surpassed the water intake in the first 15 min.2. The delay of 15, 30 or 60 min after injection of isoprenaline, 100 mug/kg, before drinking was allowed, significantly reduced saline intake but did not modify the amount of water subsequently drunk.3. Isoprenaline caused a sudden drop in arterial blood pressure, the extent and duration depending on the dose. The time of maximum drop 3-4 min after injection coincided with the time the rat drank salt.4. Isoprenaline-induced saline drinking was significantly reduced after bilateral nephrectomy but water intake was unaffected.5. The beta-adrenoceptor blocking agent, propranolol, inhibited isoprenaline-induced NaCl and water intake, while the alpha-adrenoceptor antagonist phenoxybenzamine abolished isoprenaline-induced NaCl intake and enhanced water intake.6. Saralasin acetate (P-113), a competitive inhibitor of angiotensin II, given into the third brain ventricle, prevented the isoprenaline-induced NaCl and water intake as well as angiotensin II-induced drinking. The angiotensin converting enzyme inhibitor SQ-20881 reduced the isoprenaline-induced NaCl and water intake.7. In conclusion, hypotension might be a component of salt drinking evoked by isoprenaline although the dipsogenic action of beta-stimulation is mainly due to endogenous renin-angiotensin activation.", "contents": "Drinking behaviour in rats treated with isoprenaline, angiotensin II or angiotensin antagonists. 1. Isoprenaline hydrochloride injected subcutaneously in rats given a choice test of 1.8% NaCl and water, first induced saline intake which started immediately and was almost concluded in 15 min, followed by a copious water intake. When either saline or water were given in a separate test, saline intake surpassed the water intake in the first 15 min.2. The delay of 15, 30 or 60 min after injection of isoprenaline, 100 mug/kg, before drinking was allowed, significantly reduced saline intake but did not modify the amount of water subsequently drunk.3. Isoprenaline caused a sudden drop in arterial blood pressure, the extent and duration depending on the dose. The time of maximum drop 3-4 min after injection coincided with the time the rat drank salt.4. Isoprenaline-induced saline drinking was significantly reduced after bilateral nephrectomy but water intake was unaffected.5. The beta-adrenoceptor blocking agent, propranolol, inhibited isoprenaline-induced NaCl and water intake, while the alpha-adrenoceptor antagonist phenoxybenzamine abolished isoprenaline-induced NaCl intake and enhanced water intake.6. Saralasin acetate (P-113), a competitive inhibitor of angiotensin II, given into the third brain ventricle, prevented the isoprenaline-induced NaCl and water intake as well as angiotensin II-induced drinking. The angiotensin converting enzyme inhibitor SQ-20881 reduced the isoprenaline-induced NaCl and water intake.7. In conclusion, hypotension might be a component of salt drinking evoked by isoprenaline although the dipsogenic action of beta-stimulation is mainly due to endogenous renin-angiotensin activation."}
{"id": "PMID:231101", "title": "The relationship between end-plate size and transmitter release in normal and dystrophic muscles of the mouse.", "content": "1. The morphology of nerve terminals and sub-neural apparatuses was examined in the muscles of normal and dystrophic adult mice of the Bar Harbor 129 ReJ strain. Nerve terminals were larger in dystrophic muscles than in normal muscles and nerve terminal sprouting was evident in about 50% of the dystrophic muscles fibres. End-plate area was positively correlated with muscle fibre diameter in both normal and dystrophic muscles. 2. Polynueronal innervation was found  in only 1% of dystrophic muscle fibres impaled with micro-electrodes. 3. Miniature end-plate potential amplitude was positively correlated with muscle fibre input resistance in both normal and dystrophic muscles. There was however, a greater than normal variation in the amplitudes of m.e.p.p.s recorded from individual dystrophic muscle fibres. 4. Quantum contents of end-plate potentials were estimated in normal and dystrophic mouse nerve-muscle preparations partially blocked with D-tubocurarine. The quantum content of e.p.p.s seemed to be related to muscle fibre diameter, and in dystrophic muscles the characteristics of evoked release were indistinguishable from normal. 5. It was concluded that the nerve terminal sprouting and the expansion of end-plate area which were observed in dystrophic muscles are not a consequence of any form of denervation, but represent an attempt by the axon to expand the area of synaptic contact in hypertrophied muscle fibres.", "contents": "The relationship between end-plate size and transmitter release in normal and dystrophic muscles of the mouse. 1. The morphology of nerve terminals and sub-neural apparatuses was examined in the muscles of normal and dystrophic adult mice of the Bar Harbor 129 ReJ strain. Nerve terminals were larger in dystrophic muscles than in normal muscles and nerve terminal sprouting was evident in about 50% of the dystrophic muscles fibres. End-plate area was positively correlated with muscle fibre diameter in both normal and dystrophic muscles. 2. Polynueronal innervation was found  in only 1% of dystrophic muscle fibres impaled with micro-electrodes. 3. Miniature end-plate potential amplitude was positively correlated with muscle fibre input resistance in both normal and dystrophic muscles. There was however, a greater than normal variation in the amplitudes of m.e.p.p.s recorded from individual dystrophic muscle fibres. 4. Quantum contents of end-plate potentials were estimated in normal and dystrophic mouse nerve-muscle preparations partially blocked with D-tubocurarine. The quantum content of e.p.p.s seemed to be related to muscle fibre diameter, and in dystrophic muscles the characteristics of evoked release were indistinguishable from normal. 5. It was concluded that the nerve terminal sprouting and the expansion of end-plate area which were observed in dystrophic muscles are not a consequence of any form of denervation, but represent an attempt by the axon to expand the area of synaptic contact in hypertrophied muscle fibres."}
{"id": "PMID:231103", "title": "The packeted release of transmitter from the sympathetic nerves of the guinea-pig vas deferens: an electrophysiological study.", "content": "1. Excitatory junction potentials (e.j.p.s) were recorded intracellularly in the guinea-pig vas deferens following stimulation of the hypogastric nerve. Differentiation of the rising phase of the e.j.p. showed them to be made up of transient peaks in the rate of depolarisation, the 'discrete events'. 2. In any one cell discrete events occurred at one or several latencies, intermittently, the frequency of occurrence varying between 1 in 1.8 to 1 in 45 stimuli. 3. Intermittence was not an artifact due to the use of submaximal stimulation nor the result of a ganglionic relay between the hypogastric and vas deferens nerve. 4. Discrete events occurring with a single latency had amplitudes that were multimodally distributed. In some cells the preferred values of amplitude were simple whole number multiples of the smallest preferred value. 5. The time course of discrete events varied from cell to cell and at different latencies. The discrete event had a time to peak of 5.3 +/- 1.9 msec, n = 220 (mean +/- S.D.) and a time to half decay of 8.3 +/- 3.6 msec, n = 220. 6. Discrete events in a cell could be matched for amplitude and time course by spontaneous excitatory junction potentials in the same cell and both probably represent the release of a single packet of transmitter. 7. The e.j.p. is made up of (1) discrete events which represent the release of transmitter from a single varicosity, (2) a non intermittent slow component which represents the electronic spread of activity from smooth muscle excited from distant release sites. 8. It is concluded that transmitter release from individual varicosities is packeted and the number of packets liberated per stimulus from a single varicosity is small, varying between zero and 10.", "contents": "The packeted release of transmitter from the sympathetic nerves of the guinea-pig vas deferens: an electrophysiological study. 1. Excitatory junction potentials (e.j.p.s) were recorded intracellularly in the guinea-pig vas deferens following stimulation of the hypogastric nerve. Differentiation of the rising phase of the e.j.p. showed them to be made up of transient peaks in the rate of depolarisation, the 'discrete events'. 2. In any one cell discrete events occurred at one or several latencies, intermittently, the frequency of occurrence varying between 1 in 1.8 to 1 in 45 stimuli. 3. Intermittence was not an artifact due to the use of submaximal stimulation nor the result of a ganglionic relay between the hypogastric and vas deferens nerve. 4. Discrete events occurring with a single latency had amplitudes that were multimodally distributed. In some cells the preferred values of amplitude were simple whole number multiples of the smallest preferred value. 5. The time course of discrete events varied from cell to cell and at different latencies. The discrete event had a time to peak of 5.3 +/- 1.9 msec, n = 220 (mean +/- S.D.) and a time to half decay of 8.3 +/- 3.6 msec, n = 220. 6. Discrete events in a cell could be matched for amplitude and time course by spontaneous excitatory junction potentials in the same cell and both probably represent the release of a single packet of transmitter. 7. The e.j.p. is made up of (1) discrete events which represent the release of transmitter from a single varicosity, (2) a non intermittent slow component which represents the electronic spread of activity from smooth muscle excited from distant release sites. 8. It is concluded that transmitter release from individual varicosities is packeted and the number of packets liberated per stimulus from a single varicosity is small, varying between zero and 10."}
{"id": "PMID:231105", "title": "[Endolymphatic curietherapy by lymphography with labelled lipiodol in Hodgkin's disease. A report on 408 cases (author's transl)].", "content": "The results of 373 lymphography examinations with radioactive lipiodol, conducted in 408 patients with Hodgkin's disease for diagnostic and prophylactic therapeutic purposes, during investigations carried out from 1966 to 1973 are analyzed. Tolerance was always excellent, especially from the hematological point of view. The efficacy of the procedure can be assessed by the fact that there were only 6% of failures (21/373) in glandular regions irradiated in this way for prophylactic purposes. Relapses occur more frequently in the inguino-iliac and lumbo-aortic regions than in the pelvic chains which were perfectly protected. This technique also enables both pelvic irradiation and ovarian protection in young women without any risk of failure. The procedure is particularly indicated in the following cases: supradiaphragmatic stages I and II, whatever the sex, and stage III especially in women. In sub-diaphragmatic stages I and II, it allows, in favourable cases, the ovarian function in women to remain intact by limiting external irradiation to invaded regions only.", "contents": "[Endolymphatic curietherapy by lymphography with labelled lipiodol in Hodgkin's disease. A report on 408 cases (author's transl)]. The results of 373 lymphography examinations with radioactive lipiodol, conducted in 408 patients with Hodgkin's disease for diagnostic and prophylactic therapeutic purposes, during investigations carried out from 1966 to 1973 are analyzed. Tolerance was always excellent, especially from the hematological point of view. The efficacy of the procedure can be assessed by the fact that there were only 6% of failures (21/373) in glandular regions irradiated in this way for prophylactic purposes. Relapses occur more frequently in the inguino-iliac and lumbo-aortic regions than in the pelvic chains which were perfectly protected. This technique also enables both pelvic irradiation and ovarian protection in young women without any risk of failure. The procedure is particularly indicated in the following cases: supradiaphragmatic stages I and II, whatever the sex, and stage III especially in women. In sub-diaphragmatic stages I and II, it allows, in favourable cases, the ovarian function in women to remain intact by limiting external irradiation to invaded regions only."}
{"id": "PMID:231114", "title": "Granular cell myoblastoma of the vulva.", "content": "The granular cell myoblastoma (granular cell tumor) is a rare lesion of mesodermal origin that occurs in many areas of the body, including the vulva in seven percent of cases. The exact origin of this tumor is still being investigated. However, nerve cell origin is generally accepted. Lesions of the vulva occur in any age group and must be biopsied to rule out carcinoma, hidradenomas, sebaceous cysts, and papillomas. The recurrence rate of incompletely excised lesions is 25 percent. The microscopic picture of the lesion may simulate carcinoma as a result of reactive hyperplasia of the overlying epidermis. Discovery of a mass on the vulva in any patient which on biopsy reveals a granular cell myoblastoma should lead the examiner to excise the lesion completely and also to search for other lesions at various sites of the body.", "contents": "Granular cell myoblastoma of the vulva. The granular cell myoblastoma (granular cell tumor) is a rare lesion of mesodermal origin that occurs in many areas of the body, including the vulva in seven percent of cases. The exact origin of this tumor is still being investigated. However, nerve cell origin is generally accepted. Lesions of the vulva occur in any age group and must be biopsied to rule out carcinoma, hidradenomas, sebaceous cysts, and papillomas. The recurrence rate of incompletely excised lesions is 25 percent. The microscopic picture of the lesion may simulate carcinoma as a result of reactive hyperplasia of the overlying epidermis. Discovery of a mass on the vulva in any patient which on biopsy reveals a granular cell myoblastoma should lead the examiner to excise the lesion completely and also to search for other lesions at various sites of the body."}
{"id": "PMID:231115", "title": "Action of exogenously administered steroid hormones following perinatal exposure to polybrominated biphenyls.", "content": "Polybrominated biphenyls (PBBs) have produced a variety of effects including alterations in the endocrine system and in the activity of microsomal mixed-function oxidases (MFOs). Because steroid hormones are substrates for MFOs, effects of PBBs on the endocrine system may be a consequence of enhanced steroid hormone catabolism. Therefore, as a first step in evaluating the effect of PBBs on steroid hormone catabolism. Therefore, as a first step in evaluating the effect of PBBs on steroid hormone metabolism, it was of interest to determine effects of perinatal exposure to PBBs on the response to exogenously adminstered steroid hormones. Rats were exposed to 0, 10, or 100 ppm PBBs from d 8 of gestation until d 28 postpartum, when experiments were conducted. Responses to labeled steroid hormones were generally modified in a manner directly related to PBB dose and were correlated with changes in serum and target tissue retroactivity. Stimulated metabolism of steroid hormones may account, at least in part, for endocrine-related alterations produced by PBBs. Although the potential for decreased reproductive capacity following PBBs cannot yet be accurately predicted, these experiments suggest that fertility may be reduced following PBBs as a consequence of accelerated steroid hormone metabolism and/or excretion.", "contents": "Action of exogenously administered steroid hormones following perinatal exposure to polybrominated biphenyls. Polybrominated biphenyls (PBBs) have produced a variety of effects including alterations in the endocrine system and in the activity of microsomal mixed-function oxidases (MFOs). Because steroid hormones are substrates for MFOs, effects of PBBs on the endocrine system may be a consequence of enhanced steroid hormone catabolism. Therefore, as a first step in evaluating the effect of PBBs on steroid hormone catabolism. Therefore, as a first step in evaluating the effect of PBBs on steroid hormone metabolism, it was of interest to determine effects of perinatal exposure to PBBs on the response to exogenously adminstered steroid hormones. Rats were exposed to 0, 10, or 100 ppm PBBs from d 8 of gestation until d 28 postpartum, when experiments were conducted. Responses to labeled steroid hormones were generally modified in a manner directly related to PBB dose and were correlated with changes in serum and target tissue retroactivity. Stimulated metabolism of steroid hormones may account, at least in part, for endocrine-related alterations produced by PBBs. Although the potential for decreased reproductive capacity following PBBs cannot yet be accurately predicted, these experiments suggest that fertility may be reduced following PBBs as a consequence of accelerated steroid hormone metabolism and/or excretion."}
{"id": "PMID:231116", "title": "Biochemical alterations in livers of rats exposed to vinyl chloride.", "content": "Sprague-Dawley rats were exposed to vinyl chloride to determine the earliest sequential biochemical changes occurring with liver injury before anglosarcoma development. Activity of glucose-6-phosphatase, a key gluconeogenic enzyme in the liver microsomal fraction, decreased 25% with respect to controls after 70 h of exposure. Glucose-6-phosphate dehydrogenase activity increased twofold after more than 100 h of exposure. Nonprotein sulfhydryl levels (glutathione and/or cysteine) showed a slight but progressive elevation, whereas glutathione reductase activity increased 50-60% during exposure to vinyl chloride.NADPH-cytochrome c reductase and mixed function oxidase were unchanged in the same microsomal fraction. There markers of liver mitochondrial, cytosol, and microsomal function. No significant histological changes were found on light microscopic examination during this exposure period. However, with electron microscopy, dilation of rough endoplasmic reticulum was seen in the animals exposed for more than 137 h. These enzymatic changes are considered to reflect early hepatocellular adaptation to vinyl chloride exposure with very mild or limited hepatocellular injury in its earliest stage.", "contents": "Biochemical alterations in livers of rats exposed to vinyl chloride. Sprague-Dawley rats were exposed to vinyl chloride to determine the earliest sequential biochemical changes occurring with liver injury before anglosarcoma development. Activity of glucose-6-phosphatase, a key gluconeogenic enzyme in the liver microsomal fraction, decreased 25% with respect to controls after 70 h of exposure. Glucose-6-phosphate dehydrogenase activity increased twofold after more than 100 h of exposure. Nonprotein sulfhydryl levels (glutathione and/or cysteine) showed a slight but progressive elevation, whereas glutathione reductase activity increased 50-60% during exposure to vinyl chloride.NADPH-cytochrome c reductase and mixed function oxidase were unchanged in the same microsomal fraction. There markers of liver mitochondrial, cytosol, and microsomal function. No significant histological changes were found on light microscopic examination during this exposure period. However, with electron microscopy, dilation of rough endoplasmic reticulum was seen in the animals exposed for more than 137 h. These enzymatic changes are considered to reflect early hepatocellular adaptation to vinyl chloride exposure with very mild or limited hepatocellular injury in its earliest stage."}
{"id": "PMID:231117", "title": "Toxic effects of cadmium on the developing rat lung. I. Altered pulmonary surfactant and the induction of respiratory distress syndrome.", "content": "The effects of Cd on the growth of the fetal rat lung and the maturation of the pulmonary surfactant system were studied. Pregnant rats received sc injections of cadmium chloride on d 12-15 of gestation. Animals were sacrificed throughout late gestation. Fetal lungs were assayed for pulmonary surfactant lecithin and spingomyelin. Some animals were allowed to give birth and the neonates were observed for symptoms of respiratory distress. The treatment resulted in high fetal mortality and growth retardation. Lung-body weight ratios were reduced by 20-30% in treated fetuses. Pulmonary spingomyelin content was not affected by the Cd absolute quantity but not in lecithin-lung weight ratio on the last days of gestation. Parturition was delayed almost a full day by the Dd treatment, and birth weights were reduced. Of the treated neonates, 11% developed respiratory distress syndrome. All but one of these individuals died and had lungs with hyaline membranes. Prenatal exposure to Cd can (1) cause lung hypoplasia, (2) affect pulmonary surfactant, and (3) induce respiratory distress syndrome in term pups.", "contents": "Toxic effects of cadmium on the developing rat lung. I. Altered pulmonary surfactant and the induction of respiratory distress syndrome. The effects of Cd on the growth of the fetal rat lung and the maturation of the pulmonary surfactant system were studied. Pregnant rats received sc injections of cadmium chloride on d 12-15 of gestation. Animals were sacrificed throughout late gestation. Fetal lungs were assayed for pulmonary surfactant lecithin and spingomyelin. Some animals were allowed to give birth and the neonates were observed for symptoms of respiratory distress. The treatment resulted in high fetal mortality and growth retardation. Lung-body weight ratios were reduced by 20-30% in treated fetuses. Pulmonary spingomyelin content was not affected by the Cd absolute quantity but not in lecithin-lung weight ratio on the last days of gestation. Parturition was delayed almost a full day by the Dd treatment, and birth weights were reduced. Of the treated neonates, 11% developed respiratory distress syndrome. All but one of these individuals died and had lungs with hyaline membranes. Prenatal exposure to Cd can (1) cause lung hypoplasia, (2) affect pulmonary surfactant, and (3) induce respiratory distress syndrome in term pups."}
{"id": "PMID:231119", "title": "Juvenile nasopharyngeal angiofibroma.", "content": "A case of juvenile nasopharyngeal angiofibroma in a 14 year old boy is presented on account of the endocrinological investigation performed before, during, and after treatment with 15 mg/day diethylstilbestrol for more than one month. Previously, the tumor had recurred in spite of extensive surgery. Secondary sexual characteristics were normal and the development of puberty at the age of 12-13 years seemed not to have influenced tumor growth. In contrast to certain previous reports, normal functions were found regarding the pituitary, the gonads, the adrenal cortex, and the thyroid gland in our patient. The tumor continued to grow in spite of the diethylstilbestrol therapy.", "contents": "Juvenile nasopharyngeal angiofibroma. A case of juvenile nasopharyngeal angiofibroma in a 14 year old boy is presented on account of the endocrinological investigation performed before, during, and after treatment with 15 mg/day diethylstilbestrol for more than one month. Previously, the tumor had recurred in spite of extensive surgery. Secondary sexual characteristics were normal and the development of puberty at the age of 12-13 years seemed not to have influenced tumor growth. In contrast to certain previous reports, normal functions were found regarding the pituitary, the gonads, the adrenal cortex, and the thyroid gland in our patient. The tumor continued to grow in spite of the diethylstilbestrol therapy."}
{"id": "PMID:231120", "title": "Endoscopic findings in sleep apnea syndrome.", "content": "Sleep apnea syndrome is a constellation of symptoms resulting from recurrent episodes of apnea during sleep. Often the upper airway becomes obstructed during slumber in this disorder. Symptoms relate to sleep deprivation and include morning headaches, daytime somnolence, personality changes with deteriorating intellectual capacity, nocturnal enuresis, and sexual dysfunction. Diagnosis is assisted by polysomnographic recordings. Therapy is directed at the cause of obstruction when one can be found, weight loss in massively obese patients, tracheostomy in the symptomatic patient. Four patients with documented sleep apnea syndrome are discussed. One patient, a thin adolescent female underwent adenoidectomy without improvement. Two massively obese adult males required tracheostomy with marked amelioration of symptoms. One additional adult male was found to have sleep apnea due to severe, acquired micrognathia; he was significantly improved by tracheostomy. All three adult patients were found by endoscopic visualization to have marked pharyngeal soft tissue collapse with inspiration during apneic episodes. Possible causes of pharyngeal collapse are discussed.", "contents": "Endoscopic findings in sleep apnea syndrome. Sleep apnea syndrome is a constellation of symptoms resulting from recurrent episodes of apnea during sleep. Often the upper airway becomes obstructed during slumber in this disorder. Symptoms relate to sleep deprivation and include morning headaches, daytime somnolence, personality changes with deteriorating intellectual capacity, nocturnal enuresis, and sexual dysfunction. Diagnosis is assisted by polysomnographic recordings. Therapy is directed at the cause of obstruction when one can be found, weight loss in massively obese patients, tracheostomy in the symptomatic patient. Four patients with documented sleep apnea syndrome are discussed. One patient, a thin adolescent female underwent adenoidectomy without improvement. Two massively obese adult males required tracheostomy with marked amelioration of symptoms. One additional adult male was found to have sleep apnea due to severe, acquired micrognathia; he was significantly improved by tracheostomy. All three adult patients were found by endoscopic visualization to have marked pharyngeal soft tissue collapse with inspiration during apneic episodes. Possible causes of pharyngeal collapse are discussed."}
{"id": "PMID:231121", "title": "Supplemental arginine increases thymic cellularity in normal and murine sarcoma virus-inoculated mice and increases the resistance to murine sarcoma virus tumor.", "content": "Arginine supplements were given to 6 week old CBA mice beginning 3 days prior to inoculation with a murine sarcoma virus, the Moloney Sarcoma Virus (MSV). Although the basal diet contained 1.8% arginine and was therefore not arginine-deficient, supplementation of the diet and the drinking water with 0.5% arginine HCl reduced tumor incidence, lengthened the latency period, decreased tumor size, and hastened tumor regression. Arginine also increased thymic weight and cellularity in normal and in MSV-inoculated mice. The antitumor action of arginine may be related to its effect on the thymus.", "contents": "Supplemental arginine increases thymic cellularity in normal and murine sarcoma virus-inoculated mice and increases the resistance to murine sarcoma virus tumor. Arginine supplements were given to 6 week old CBA mice beginning 3 days prior to inoculation with a murine sarcoma virus, the Moloney Sarcoma Virus (MSV). Although the basal diet contained 1.8% arginine and was therefore not arginine-deficient, supplementation of the diet and the drinking water with 0.5% arginine HCl reduced tumor incidence, lengthened the latency period, decreased tumor size, and hastened tumor regression. Arginine also increased thymic weight and cellularity in normal and in MSV-inoculated mice. The antitumor action of arginine may be related to its effect on the thymus."}
{"id": "PMID:231153", "title": "Age-related changes in the immune system of mice of eight medium and long-lived strains and hybrids. II. Short- and long-term effects of natural infection with parainfluenza type 1 virus (Sendai).", "content": "Studies on the effects of natural infection with parainfluenza type 1 virus (Sendai) on the immune system of 8 strains and hybrids of aging mice revealed that (a) 55 of 63 indices tested were abnormal as late as 8 months after the disappearance of clinical systoms, (b) thymus weight and cell indices and lymph node T cell activity still exhibited a statistically significant negative correlation with age following infection, and (c) immunologically immature young and immunodeficient old mice suffered more severe sequelae following viral infection than did adult or middle-aged mice as determined by accelerated decline of thymus indices, mortality, IgM Coombs' titer, and in the case of old mice, anemia. These findings suggest that chronic viral infection can accelerate immunologic aging and that viral infection in utero can suppress or retard the development of the T cell component of the immune system. In support of our previous study, they also suggest that the thymus regulates immunologic aging and that genetic factors regulating immunologic aging are not easily influenced by environmental factors.", "contents": "Age-related changes in the immune system of mice of eight medium and long-lived strains and hybrids. II. Short- and long-term effects of natural infection with parainfluenza type 1 virus (Sendai). Studies on the effects of natural infection with parainfluenza type 1 virus (Sendai) on the immune system of 8 strains and hybrids of aging mice revealed that (a) 55 of 63 indices tested were abnormal as late as 8 months after the disappearance of clinical systoms, (b) thymus weight and cell indices and lymph node T cell activity still exhibited a statistically significant negative correlation with age following infection, and (c) immunologically immature young and immunodeficient old mice suffered more severe sequelae following viral infection than did adult or middle-aged mice as determined by accelerated decline of thymus indices, mortality, IgM Coombs' titer, and in the case of old mice, anemia. These findings suggest that chronic viral infection can accelerate immunologic aging and that viral infection in utero can suppress or retard the development of the T cell component of the immune system. In support of our previous study, they also suggest that the thymus regulates immunologic aging and that genetic factors regulating immunologic aging are not easily influenced by environmental factors."}
{"id": "PMID:231158", "title": "[Prenatal causes of sensorineural hearing loss in children (author's transl)].", "content": "Prenatal causes of sensorineural hearing loss in children may be genetic or nongenetic, the deafness occurs alone or with other abnormalities. In addition, there are prenatal causes of a sensorineural hearing loss which is of delayed onset postnatally. In this review only the better known causes are discussed in which the otorhinolaryngologist should establish a diagnosis early, particularly when the possibility exists of preventing or even treating the hearing loss.", "contents": "[Prenatal causes of sensorineural hearing loss in children (author's transl)]. Prenatal causes of sensorineural hearing loss in children may be genetic or nongenetic, the deafness occurs alone or with other abnormalities. In addition, there are prenatal causes of a sensorineural hearing loss which is of delayed onset postnatally. In this review only the better known causes are discussed in which the otorhinolaryngologist should establish a diagnosis early, particularly when the possibility exists of preventing or even treating the hearing loss."}
{"id": "PMID:231159", "title": "[Viral infection and sudden perceptive deafness (serological examinations) (author's transl)].", "content": "Among the numerous and various known etiologies of sudden deafness viral infection is discussed. Therefore sera of 126 patients were examined for viral antibodies to Influenza, Parainfluenza, Mumps, Measles, RS-virus, Rubella, Herpesvirus and Adenovirus. They were compared to sera of healthy patients. Our results suggest no strong association between sudden deafness and viral infection.", "contents": "[Viral infection and sudden perceptive deafness (serological examinations) (author's transl)]. Among the numerous and various known etiologies of sudden deafness viral infection is discussed. Therefore sera of 126 patients were examined for viral antibodies to Influenza, Parainfluenza, Mumps, Measles, RS-virus, Rubella, Herpesvirus and Adenovirus. They were compared to sera of healthy patients. Our results suggest no strong association between sudden deafness and viral infection."}
{"id": "PMID:231160", "title": "[Cervical synovial sarcoma in children (author's transl)].", "content": "Cervical synovial sarcoma is a rather uncommon neoplasm in children. Until to date 10 such cases have been reported. We describe an additional patient in whom this lesion occurred as a primary neoplasm of the hypopharynx.", "contents": "[Cervical synovial sarcoma in children (author's transl)]. Cervical synovial sarcoma is a rather uncommon neoplasm in children. Until to date 10 such cases have been reported. We describe an additional patient in whom this lesion occurred as a primary neoplasm of the hypopharynx."}
{"id": "PMID:231174", "title": "Lipid composition of SV40-induced transplantable hamster tumor.", "content": "The analysis of the lipid composition of the SV40-induced transplantable hamster tumor has shown that: (a) the total phospholipid content in the tumor is lower than that usually found in normal tissues and similar to that reported for other neoplasms; (b) except for a lower percentage of diphosphatidylglycerol, the phospholipid composition is comparable with that reported for normal tissues; (c) the fatty acid profiles of the various glycerophospholipid classes are characterized by high proportions of oleic acid; and (d) phosphatidylethanolamine contains proportions of alkenyl side chains which are consistent with the amounts of plasmalogenic phospholipids found in other neoplasms.", "contents": "Lipid composition of SV40-induced transplantable hamster tumor. The analysis of the lipid composition of the SV40-induced transplantable hamster tumor has shown that: (a) the total phospholipid content in the tumor is lower than that usually found in normal tissues and similar to that reported for other neoplasms; (b) except for a lower percentage of diphosphatidylglycerol, the phospholipid composition is comparable with that reported for normal tissues; (c) the fatty acid profiles of the various glycerophospholipid classes are characterized by high proportions of oleic acid; and (d) phosphatidylethanolamine contains proportions of alkenyl side chains which are consistent with the amounts of plasmalogenic phospholipids found in other neoplasms."}
{"id": "PMID:231173", "title": "Ethanolamine kinase activity and compositions of diacylglycerols, phosphatidylcholines and phosphatidylethanolamines in livers of choline-deficient rats.", "content": "These experiments were performed to find the reasons for the increased concentrations of docosahexaenoyl phosphatidylethanolamines (PE) in livers of choline-deficient rats. We measured the activity of ethanolamine kinase, which catalyzes the first step in PE formation. We also measured the compositions of PE and phosphatidylcholines (PC) and concentrations and fatty acid compositions of diacylglycerols (DG), which are precursors of PE. Young male rats were fed for one week a low-methionine, choline-deficient diet, or the same diet supplemented with choline. Ethanolamine kinase activity was measured in liver cytosol (100,000 g supernatant). Fatty acids were measured in total liver diacylglycerols and in microsomal PE and PC. Ethanolamine kinase activities were equal in choline-deficient and choline-supplemented rats. Concentrations of DG were elevated 6-fold by choline deficiency. The percentage of docosahexaenoic acid (22:6n-3) in microsomal PE was nearly doubled by choline deficiency. Although the increased concentrations of PE in choline-deficient livers cannot be attributed to increased activity of ethanolamine kinase, the rate of PE formation probably was increased by increases in concentrations of its precursors, including DG. The disproportionate increase in 22:6n-3 PE probably was caused by a selective formation of PE from DG that contain 22:6n-3.", "contents": "Ethanolamine kinase activity and compositions of diacylglycerols, phosphatidylcholines and phosphatidylethanolamines in livers of choline-deficient rats. These experiments were performed to find the reasons for the increased concentrations of docosahexaenoyl phosphatidylethanolamines (PE) in livers of choline-deficient rats. We measured the activity of ethanolamine kinase, which catalyzes the first step in PE formation. We also measured the compositions of PE and phosphatidylcholines (PC) and concentrations and fatty acid compositions of diacylglycerols (DG), which are precursors of PE. Young male rats were fed for one week a low-methionine, choline-deficient diet, or the same diet supplemented with choline. Ethanolamine kinase activity was measured in liver cytosol (100,000 g supernatant). Fatty acids were measured in total liver diacylglycerols and in microsomal PE and PC. Ethanolamine kinase activities were equal in choline-deficient and choline-supplemented rats. Concentrations of DG were elevated 6-fold by choline deficiency. The percentage of docosahexaenoic acid (22:6n-3) in microsomal PE was nearly doubled by choline deficiency. Although the increased concentrations of PE in choline-deficient livers cannot be attributed to increased activity of ethanolamine kinase, the rate of PE formation probably was increased by increases in concentrations of its precursors, including DG. The disproportionate increase in 22:6n-3 PE probably was caused by a selective formation of PE from DG that contain 22:6n-3."}
{"id": "PMID:231175", "title": "[Human trypanosomiasis focus of Vavoua (Ivory Coast). A clinical, parasitological and sero-immunological survey (author's transl)].", "content": "Vavoua human trypanosomiasis focus, located 60 km north of Daloa (Ivory Coast Republic) is facing a period of hyperactivity. A medical survey has been conducted in 9 villages of this focus: 7.424 persons have been examined and 128 new cases diagnosed in the field after clinical and parasitological examinations. Indirect Fluorescence Antibody Test applied to dried blood blots, in the laboratory, revealed 266 immunological suspects to be reexamined. 185 suspects were reexamined, 104 of whom were diagnosed after tyrpanosomes had been found in blood or/and in gland juice. The microhaematocrit centrifuge technique gave good results. Most of the 232 new cases were in the classical first period (unaltered CSF). Authors are insisting on the importance of survey prospections allowing an early diagnosis of sleeping sickness and on the interest of an immunodiagnostic test in addition to classical techniques to diagnose asymptomatical forms.", "contents": "[Human trypanosomiasis focus of Vavoua (Ivory Coast). A clinical, parasitological and sero-immunological survey (author's transl)]. Vavoua human trypanosomiasis focus, located 60 km north of Daloa (Ivory Coast Republic) is facing a period of hyperactivity. A medical survey has been conducted in 9 villages of this focus: 7.424 persons have been examined and 128 new cases diagnosed in the field after clinical and parasitological examinations. Indirect Fluorescence Antibody Test applied to dried blood blots, in the laboratory, revealed 266 immunological suspects to be reexamined. 185 suspects were reexamined, 104 of whom were diagnosed after tyrpanosomes had been found in blood or/and in gland juice. The microhaematocrit centrifuge technique gave good results. Most of the 232 new cases were in the classical first period (unaltered CSF). Authors are insisting on the importance of survey prospections allowing an early diagnosis of sleeping sickness and on the interest of an immunodiagnostic test in addition to classical techniques to diagnose asymptomatical forms."}
{"id": "PMID:231177", "title": "[Contribution of immunoglobulin assays to the diagnosis of human African trypanosomiasis in patients immunologically suspect (immunofluorescence and ELISA). A preliminary report (author's transl)].", "content": "Can the diagnosis of sleeping sickness in patients immunologically suspect, without seeing the parasite, be obtained by dosing IgG and IgM? The authors demonstrate that two groups of people with positive immunodiagnosis, one parasitologically confirmed and the other not confirmed, do not show significant difference when dosing immunoglobulins. These two groups respectively show a significant difference when compared with a parasitologically and immunologicaly negative group. The simultaneous increase in IgG and IgM might confirm the immunodiagnosis.", "contents": "[Contribution of immunoglobulin assays to the diagnosis of human African trypanosomiasis in patients immunologically suspect (immunofluorescence and ELISA). A preliminary report (author's transl)]. Can the diagnosis of sleeping sickness in patients immunologically suspect, without seeing the parasite, be obtained by dosing IgG and IgM? The authors demonstrate that two groups of people with positive immunodiagnosis, one parasitologically confirmed and the other not confirmed, do not show significant difference when dosing immunoglobulins. These two groups respectively show a significant difference when compared with a parasitologically and immunologicaly negative group. The simultaneous increase in IgG and IgM might confirm the immunodiagnosis."}
{"id": "PMID:231176", "title": "[Comparative value of ELISA technique and immunofluorescence for the detection in the foci of human African trypanosomiasis].", "content": "As the parasitological diagnosis method consisting in the detection of the parasite in people suffering from sleeping sickness did not prove entirely reliable, the authors have tested a new immunoenzymatic diagnosis method called ELISA. 41 sera from clinical suspects have been tested (parasite having been found in 16 of them). Positive and negative levels have been tested by comparison with indirect immunofluorescence. The following results, given in optical density, have been obtained: negative cases less than 36 less than or equal to uncertain cases less than or equal to 40 less than positive cases. When using these date, correlation with immunofluorescence proves to be excellent with a sensibility between 95 and 97,5 p. 100 and a specificity between 97,5 and 99 p. 100.", "contents": "[Comparative value of ELISA technique and immunofluorescence for the detection in the foci of human African trypanosomiasis]. As the parasitological diagnosis method consisting in the detection of the parasite in people suffering from sleeping sickness did not prove entirely reliable, the authors have tested a new immunoenzymatic diagnosis method called ELISA. 41 sera from clinical suspects have been tested (parasite having been found in 16 of them). Positive and negative levels have been tested by comparison with indirect immunofluorescence. The following results, given in optical density, have been obtained: negative cases less than 36 less than or equal to uncertain cases less than or equal to 40 less than positive cases. When using these date, correlation with immunofluorescence proves to be excellent with a sensibility between 95 and 97,5 p. 100 and a specificity between 97,5 and 99 p. 100."}
{"id": "PMID:231178", "title": "[Antimalaria fluorescent antibodies evolution in young children living in a stable malaria area (author's transl)].", "content": "The detection of malarial fluorescent antibodies have been performed in an Abidjan dispensary on 30 newborn babies with their mothers, 30 children 3 months old and 120 children from 6 to 24 months. This survey took place during the small rainy season and it demonstrates that: --synthesis of specific antibodies is significantly starting after the 3rd month; --the rise, after six months, of the malarial antibodies is parallel to the plasmodic index checked during the same period in the same area; --the rate of antibodies in 2 years old babies is almost the same that in adults; --living conditions in rural areas accelerate the synthesis of antibodies which, adversely, is slowed down by regular chemoprophylaxis; --Plasmodium berghei is a valuable antigen for mass survey; --Abidjan town is an hypoendemic zone of stable malaria in a mesoendemic area.", "contents": "[Antimalaria fluorescent antibodies evolution in young children living in a stable malaria area (author's transl)]. The detection of malarial fluorescent antibodies have been performed in an Abidjan dispensary on 30 newborn babies with their mothers, 30 children 3 months old and 120 children from 6 to 24 months. This survey took place during the small rainy season and it demonstrates that: --synthesis of specific antibodies is significantly starting after the 3rd month; --the rise, after six months, of the malarial antibodies is parallel to the plasmodic index checked during the same period in the same area; --the rate of antibodies in 2 years old babies is almost the same that in adults; --living conditions in rural areas accelerate the synthesis of antibodies which, adversely, is slowed down by regular chemoprophylaxis; --Plasmodium berghei is a valuable antigen for mass survey; --Abidjan town is an hypoendemic zone of stable malaria in a mesoendemic area."}
{"id": "PMID:231179", "title": "[Attempt to improve the pronostic score of tetanus (author's transl)].", "content": "A prognostic score based on 6 criteria has been proposed at the 4th International Conference on Tetanus (Dakar, April 1975). A computer study of 598 cases indicates that this score may be further improved by taking into account with more accuracy the frequency of peaks of paroxism and the special severity of the intra-gluteal infection.", "contents": "[Attempt to improve the pronostic score of tetanus (author's transl)]. A prognostic score based on 6 criteria has been proposed at the 4th International Conference on Tetanus (Dakar, April 1975). A computer study of 598 cases indicates that this score may be further improved by taking into account with more accuracy the frequency of peaks of paroxism and the special severity of the intra-gluteal infection."}
{"id": "PMID:231182", "title": "Amplification of chloramphenicol resistance transposons carried by phage P1Cm in Escherichia coli.", "content": "We have characterized a number of P1Cm phages which contain the resistance genes to chloramphenicol and fusidic acid as IS1-flanked Cm transposons. Restriction cleavage and electron microscopic analysis showed that these Cm transposons were carried as monomers (M) or tandem dimers (D). Lysogens of P1Cm (D) are more resistant to chloramphenicol than those of its P1Cm (M) presumably as a result of an increased gene dosage. Amplification of the Cm transposons to tandem multimers was frequently observed in P1Cm (D) lysogens grown in the presence of high concentrations of chloramphenicol or fusidic acid and was also detected in P1Cm (M) lysogens. The degree of amplification varied in different clones which suggests that cells containing spontaneously amplified Cm transposons were selected by high doses of the antibiotics. The dimeric as well as the amplified Cm transposons carried in P1Cm lysogens grown in the absence of chloramphenicol displayed considerable stability. Mechanisms for the amplification of the IS1-flanked transposons are discussed.", "contents": "Amplification of chloramphenicol resistance transposons carried by phage P1Cm in Escherichia coli. We have characterized a number of P1Cm phages which contain the resistance genes to chloramphenicol and fusidic acid as IS1-flanked Cm transposons. Restriction cleavage and electron microscopic analysis showed that these Cm transposons were carried as monomers (M) or tandem dimers (D). Lysogens of P1Cm (D) are more resistant to chloramphenicol than those of its P1Cm (M) presumably as a result of an increased gene dosage. Amplification of the Cm transposons to tandem multimers was frequently observed in P1Cm (D) lysogens grown in the presence of high concentrations of chloramphenicol or fusidic acid and was also detected in P1Cm (M) lysogens. The degree of amplification varied in different clones which suggests that cells containing spontaneously amplified Cm transposons were selected by high doses of the antibiotics. The dimeric as well as the amplified Cm transposons carried in P1Cm lysogens grown in the absence of chloramphenicol displayed considerable stability. Mechanisms for the amplification of the IS1-flanked transposons are discussed."}
{"id": "PMID:231183", "title": "Procedure of RNA extraction which does not extract DNA and proteins from nervous tissue cells.", "content": "Several schemes of acidic extraction of RNA taken from biochemical or cytochemical literature were compared by means of ultraviolet and visible cytospectrophotometry. Basing on the data obtained an extraction scheme has been recommended which consists in the treatment of nervous tissue sections with 16 per cent perchloric acid at 4 degrees C for 48 h. This extraction has been shown to extract completely cellular RNA without extracting DNA and proteins from the nervous tissue cells. Using this scheme, ultraviolet cytospectrophotometry of neurons and glial cells was performed twice, before and after the selective RNA extraction, which enabled a calculation of RNA concentration by the difference of the absorption values. In mice, after 3 h-swimming, and in cats, after 2-week daily injections of adrenaline, a number of quantitative and qualitative RNA changes were found out in nerve and glial cell of mouse spinal cord and cat sympathetic ganglion with the aid of the recommended scheme of RNA extraction.", "contents": "Procedure of RNA extraction which does not extract DNA and proteins from nervous tissue cells. Several schemes of acidic extraction of RNA taken from biochemical or cytochemical literature were compared by means of ultraviolet and visible cytospectrophotometry. Basing on the data obtained an extraction scheme has been recommended which consists in the treatment of nervous tissue sections with 16 per cent perchloric acid at 4 degrees C for 48 h. This extraction has been shown to extract completely cellular RNA without extracting DNA and proteins from the nervous tissue cells. Using this scheme, ultraviolet cytospectrophotometry of neurons and glial cells was performed twice, before and after the selective RNA extraction, which enabled a calculation of RNA concentration by the difference of the absorption values. In mice, after 3 h-swimming, and in cats, after 2-week daily injections of adrenaline, a number of quantitative and qualitative RNA changes were found out in nerve and glial cell of mouse spinal cord and cat sympathetic ganglion with the aid of the recommended scheme of RNA extraction."}
{"id": "PMID:231188", "title": "[Phosphohydrolase activity of Pseudomonas maltophilia].", "content": "The activity of phosphohydrolase (acid, alkaline, pyrophosphatase) was studied in two strains of Pseudomonas maltophilia: VCM-B-591 and SSE-B-715. The activity of these enzyme systems in these strains was found to be much higher than in other Pseudomonas species, viz. Ps. aeruginosa VCM-B-889, Ps. fluorescens VCM-B-553, Ps. geniculata SSE-B-338, and in E. coli B. The phosphohydrolase activity of Ps. maltophilia varied depending on the growth phase of the culture. The highest activity of acid phosphatase was registered in the middle of the exponential phase for the strain VCM-B-591 and at the beginning of this phase for the strain SSE-B-715. The activity of alkaline phosphatase was maximal, for both of the strains VCM-B-591 and SSE-B-715, at the beginning of the logarithimic growth phase. The pyrophosphatase activity of the two strains had \"two peaks\" at the beginning and by the end of the logarithmic phase of growth. Incubation of Ps. maltophilia cells in media without orthophosphate did not result in an increase of their phosphohydrolase activity.", "contents": "[Phosphohydrolase activity of Pseudomonas maltophilia]. The activity of phosphohydrolase (acid, alkaline, pyrophosphatase) was studied in two strains of Pseudomonas maltophilia: VCM-B-591 and SSE-B-715. The activity of these enzyme systems in these strains was found to be much higher than in other Pseudomonas species, viz. Ps. aeruginosa VCM-B-889, Ps. fluorescens VCM-B-553, Ps. geniculata SSE-B-338, and in E. coli B. The phosphohydrolase activity of Ps. maltophilia varied depending on the growth phase of the culture. The highest activity of acid phosphatase was registered in the middle of the exponential phase for the strain VCM-B-591 and at the beginning of this phase for the strain SSE-B-715. The activity of alkaline phosphatase was maximal, for both of the strains VCM-B-591 and SSE-B-715, at the beginning of the logarithimic growth phase. The pyrophosphatase activity of the two strains had \"two peaks\" at the beginning and by the end of the logarithmic phase of growth. Incubation of Ps. maltophilia cells in media without orthophosphate did not result in an increase of their phosphohydrolase activity."}
{"id": "PMID:231199", "title": "Nucleotide-metabolizing enzymes and lymphocyte differentiation.", "content": "Inherited deficiencies of adenosine deaminase and purine nucleoside phosphorylase have been found to be associated with certain immunodeficiency syndromes which are characterized by deficiencies of mature peripheral lymphocytes. The immunodeficiency states associated with these enzyme deficiencies are thought to arise from blocks in lymphocyte differentiation. Deficiencies of these enzymes have profound and apparently selective effects on lymphocyte differentiation. Their discovery has focused attention on previously unknown relationships between purine nucleotide metabolism and lymphocyte development and function. In this article three aspects of nucleotide-metabolizing enzymes and lymphocyte differentiation will be discussed: 1) the distribution of the enzymes among lymphocyte populations at differing stages of differentiation; 2) the possible biochemical mechanisms which give rise to the immunodeficiencies; 3) the stages of lymphocyte differentiation which are affected by the enzyme deficiencies.", "contents": "Nucleotide-metabolizing enzymes and lymphocyte differentiation. Inherited deficiencies of adenosine deaminase and purine nucleoside phosphorylase have been found to be associated with certain immunodeficiency syndromes which are characterized by deficiencies of mature peripheral lymphocytes. The immunodeficiency states associated with these enzyme deficiencies are thought to arise from blocks in lymphocyte differentiation. Deficiencies of these enzymes have profound and apparently selective effects on lymphocyte differentiation. Their discovery has focused attention on previously unknown relationships between purine nucleotide metabolism and lymphocyte development and function. In this article three aspects of nucleotide-metabolizing enzymes and lymphocyte differentiation will be discussed: 1) the distribution of the enzymes among lymphocyte populations at differing stages of differentiation; 2) the possible biochemical mechanisms which give rise to the immunodeficiencies; 3) the stages of lymphocyte differentiation which are affected by the enzyme deficiencies."}
{"id": "PMID:231200", "title": "Preparation of homogeneous crystals of myo-inositol 1-phosphate synthase from rat testicles--further data on the chemical and catalytic properties of the enzyme (studies on the biosynthesis cyclitols, XXXIX).", "content": "Pre-purified preparations of myoinositol-1-phosphate synthase (E.C. 5.5.1.4) from rat testes can be purified to homogeneity by first crystallizing the enzyme according to JAKOBY and then recrystallizing it at a pH value close to the isoelectric point while slowly increasing the temperature from 0 to 15 degrees C. This method gives a much yield of homogeneous enzyme than the previously used purification by affinity chromatography. It was further found that the pure enzyme contains close to 2 mol NAD+ per mol enzyme; it does not contain any metal. At substrate saturation the enzyme binds close to 1 mol substrate per mol enzyme, as determined by using radioactively labelled substrate and binding it to the enzyme by reduction with NaBH4. The reaction catalyzed by the enzyme is irreversible.", "contents": "Preparation of homogeneous crystals of myo-inositol 1-phosphate synthase from rat testicles--further data on the chemical and catalytic properties of the enzyme (studies on the biosynthesis cyclitols, XXXIX). Pre-purified preparations of myoinositol-1-phosphate synthase (E.C. 5.5.1.4) from rat testes can be purified to homogeneity by first crystallizing the enzyme according to JAKOBY and then recrystallizing it at a pH value close to the isoelectric point while slowly increasing the temperature from 0 to 15 degrees C. This method gives a much yield of homogeneous enzyme than the previously used purification by affinity chromatography. It was further found that the pure enzyme contains close to 2 mol NAD+ per mol enzyme; it does not contain any metal. At substrate saturation the enzyme binds close to 1 mol substrate per mol enzyme, as determined by using radioactively labelled substrate and binding it to the enzyme by reduction with NaBH4. The reaction catalyzed by the enzyme is irreversible."}
{"id": "PMID:231201", "title": "Biochemical characterization of the beta-adrenergic receptor of the frog erythrocyte.", "content": "The beta-adrenergic receptor which is coupled to adenylate cyclase in the frog erythrocyte plasma membrane provides a convenient model system for probing the molecular characteristics of an adenylate cyclase coupled hormone receptor. Direct radioligand binding studies with beta-adrenergic agonists and antagonists such as [3H]hydroxybenzylisoproterenol and [3H]dihydroalprenolol have shed new light on the biochemical properties of the receptor as well as on its mode of interaction with other components of the adenylate cyclase system. Agonist binding to the receptor induces a high affinity state of the receptor which can be selectively reverted to a low agonist affinity state by guanyl nucleotides. This agonist-induced high affinity state of the receptor appears to correspond to a receptor moiety which has larger apparent molecular weight and which is probably a complex of the beta-adrenergic receptor and nucleotide regulatory binding protein. Antagonists do not appear capable of inducing or stabilizing the formation of this high affinity receptor-nucleotide site complex. The beta-adrenergic receptors have been solubilized using the plant glycoside digitonin as the detergent and have been highly purified by biospecific affinity chromatography on an alprenolol-agarose affinity support. These highly purified receptor preparations retain all of the binding characteristics observed in the unpurified soluble receptor preparations. Remarkably, antibodies raised in rabbits against affinity chromatography purified preparations of the receptor, themselves bind beta-adrenergic ligands with typical beta-adrenergic specificity. Such antibodies which possess binding sites similar to those of physiological receptors provide useful model systems for further probing the molecular characteristics of beta-adrenergic binding sites.", "contents": "Biochemical characterization of the beta-adrenergic receptor of the frog erythrocyte. The beta-adrenergic receptor which is coupled to adenylate cyclase in the frog erythrocyte plasma membrane provides a convenient model system for probing the molecular characteristics of an adenylate cyclase coupled hormone receptor. Direct radioligand binding studies with beta-adrenergic agonists and antagonists such as [3H]hydroxybenzylisoproterenol and [3H]dihydroalprenolol have shed new light on the biochemical properties of the receptor as well as on its mode of interaction with other components of the adenylate cyclase system. Agonist binding to the receptor induces a high affinity state of the receptor which can be selectively reverted to a low agonist affinity state by guanyl nucleotides. This agonist-induced high affinity state of the receptor appears to correspond to a receptor moiety which has larger apparent molecular weight and which is probably a complex of the beta-adrenergic receptor and nucleotide regulatory binding protein. Antagonists do not appear capable of inducing or stabilizing the formation of this high affinity receptor-nucleotide site complex. The beta-adrenergic receptors have been solubilized using the plant glycoside digitonin as the detergent and have been highly purified by biospecific affinity chromatography on an alprenolol-agarose affinity support. These highly purified receptor preparations retain all of the binding characteristics observed in the unpurified soluble receptor preparations. Remarkably, antibodies raised in rabbits against affinity chromatography purified preparations of the receptor, themselves bind beta-adrenergic ligands with typical beta-adrenergic specificity. Such antibodies which possess binding sites similar to those of physiological receptors provide useful model systems for further probing the molecular characteristics of beta-adrenergic binding sites."}
{"id": "PMID:231202", "title": "Lack of detectable nuclease activity in highly purified preparations of murine fibroblast interferon.", "content": "The size distribution of radiolabeled mouse C-243 cell poly-A containing RNA, and SV40 DNA was analyzed electrophoretically before and after incubation with high concentrations of electrophoretically pure murine fibroblast interferon. Using this sensitive assay, no evidence for any nuclease activity directly associated with interferon could be found, under a wide variety of incubation conditions.", "contents": "Lack of detectable nuclease activity in highly purified preparations of murine fibroblast interferon. The size distribution of radiolabeled mouse C-243 cell poly-A containing RNA, and SV40 DNA was analyzed electrophoretically before and after incubation with high concentrations of electrophoretically pure murine fibroblast interferon. Using this sensitive assay, no evidence for any nuclease activity directly associated with interferon could be found, under a wide variety of incubation conditions."}
{"id": "PMID:231203", "title": "[The use of the erythrocyte adenylate kinase system in paternity suits].", "content": "Authors describe genetically determined polymorphisms, genetical feature and pattern of inheritance of the system of AK. Results and methods used in their studies first in the Hungarian population are reported. On the basis of examination of 1734 persons the incidence of the AK phenotypes was found as follows: AK 1 = 93,59%, AK 2 = 0,05%, and AK 2-1 6,34%. Values of gene frequency: AK1-0,9676, AK2-0,0322. According to the authors findings the maximal (theoretical) chance of the exclusion of paternity on the basis of AK system was 3,02%. In 844 cases of discussed paternity beside the investigation of the systems of A1A2BO, MN, Hp, Rh, Gm/a, x, b), InV(1), Gc, Ss, Kk, Fy(ab), VSP, PGM1, GPT and ADA the system of AK was also studied. In 191 cases (22,62%) the paternity could have been excluded. In 8 cases (0,94%) exclusion of the paternity have been based on the findings of the examination of AK system. In cases of discussed paternity authors recommend the examination of the AK system.", "contents": "[The use of the erythrocyte adenylate kinase system in paternity suits]. Authors describe genetically determined polymorphisms, genetical feature and pattern of inheritance of the system of AK. Results and methods used in their studies first in the Hungarian population are reported. On the basis of examination of 1734 persons the incidence of the AK phenotypes was found as follows: AK 1 = 93,59%, AK 2 = 0,05%, and AK 2-1 6,34%. Values of gene frequency: AK1-0,9676, AK2-0,0322. According to the authors findings the maximal (theoretical) chance of the exclusion of paternity on the basis of AK system was 3,02%. In 844 cases of discussed paternity beside the investigation of the systems of A1A2BO, MN, Hp, Rh, Gm/a, x, b), InV(1), Gc, Ss, Kk, Fy(ab), VSP, PGM1, GPT and ADA the system of AK was also studied. In 191 cases (22,62%) the paternity could have been excluded. In 8 cases (0,94%) exclusion of the paternity have been based on the findings of the examination of AK system. In cases of discussed paternity authors recommend the examination of the AK system."}
{"id": "PMID:231206", "title": "Acute pulmonary paracoccidioidomycosis in an immunosuppressed patient.", "content": "A case of an acute pulmonary paracoccidioidomycosis following the use of immunosuppressive therapy in a solid cancer patient is reported.", "contents": "Acute pulmonary paracoccidioidomycosis in an immunosuppressed patient. A case of an acute pulmonary paracoccidioidomycosis following the use of immunosuppressive therapy in a solid cancer patient is reported."}
{"id": "PMID:231204", "title": "Histoenzymology of the lung. V. Histoenzymatic analysis of sixty lung tumors.", "content": "A series of sixty lung tumors operated during 1977 were histoenzymatically investigated (12 macrocellular carcionomas, 4 microcellular, 18 epidermoid, 18 cylindrocubic, 2 bronchiolo-alveolar cell carcinomas, 4 lung fibroblastic sarcomas, and 2 benign lung tumors: a haemangioma and a carcinoid tumor). There were tested 25 enzymes, hydrolases and oxidoreductases of different metabolic pathways. The histoenzymatic analysis of the neoplastic lung tissue compared with the normal adult human lung tissue pointed to a shifting of the metabolic balance, with the decrease of enzyme activities belonging to the Krebs tricarboxylic acid cycle and with the increase or maintenance of the level of enzymic activities belonging to the Embden-Meyerhoff-Parnas pathway and to the pentose shunt. The enzymes intervening in the protidic activity in all the malignant tumors of the lung. Some hydrolases were also more active lung tissue pointed out the existence of close relations between the normal epithelia and the cylindrocubic and bronchiolo-alveolar types, and of distant ones with the epidermoid and microcellular carcinomas which suffered more accentuated ecogenetic influences (stopping of differentiation/maturation, metaplasia) during the complex oncogenetic process.", "contents": "Histoenzymology of the lung. V. Histoenzymatic analysis of sixty lung tumors. A series of sixty lung tumors operated during 1977 were histoenzymatically investigated (12 macrocellular carcionomas, 4 microcellular, 18 epidermoid, 18 cylindrocubic, 2 bronchiolo-alveolar cell carcinomas, 4 lung fibroblastic sarcomas, and 2 benign lung tumors: a haemangioma and a carcinoid tumor). There were tested 25 enzymes, hydrolases and oxidoreductases of different metabolic pathways. The histoenzymatic analysis of the neoplastic lung tissue compared with the normal adult human lung tissue pointed to a shifting of the metabolic balance, with the decrease of enzyme activities belonging to the Krebs tricarboxylic acid cycle and with the increase or maintenance of the level of enzymic activities belonging to the Embden-Meyerhoff-Parnas pathway and to the pentose shunt. The enzymes intervening in the protidic activity in all the malignant tumors of the lung. Some hydrolases were also more active lung tissue pointed out the existence of close relations between the normal epithelia and the cylindrocubic and bronchiolo-alveolar types, and of distant ones with the epidermoid and microcellular carcinomas which suffered more accentuated ecogenetic influences (stopping of differentiation/maturation, metaplasia) during the complex oncogenetic process."}
{"id": "PMID:231208", "title": "Evidence for cyclic GMP-mediated relaxant effects of nitro-compounds in coronary smooth muscle.", "content": "The effects of the four nitro-compounds nitroglycerin, nitroprusside-Na, NaNO2 and B 744-99 were studied simultaneously on length and on cGMP-levels in isolated circular strips of bovine coronary arteries. 1. All 4 nitro-compounds concentration dependently relaxed the strips in close association with pronounced increases in cGMP-levels which preceded the mechanical responses. 2. The relaxant effects of all 4 nitro-compounds were significantly potentiated by the predominant inhibitor of cGMP-hydrolysis M & B 22,948, which also potentiated the increase in cGMP-levels of the two nitro-compounds in which it was studied (nitroglycerin and nitroprusside-Na). 3. Non-substituted cGMP and -- much stronger -- its 8 bromo-derivative also relaxed the strips and these effects were likewise potentiated by M & B 22,948. 4. When the log increase in cGMP produced by the 4 nitro-compounds were plotted against percent relaxation (probit scale) a linear and highly significant positive correlation was obtained. 5. The results provide evidence that the increases in cGMP caused by the 4 nitro-compounds studied are responsible for the smooth muscle relaxing actions of these drugs.", "contents": "Evidence for cyclic GMP-mediated relaxant effects of nitro-compounds in coronary smooth muscle. The effects of the four nitro-compounds nitroglycerin, nitroprusside-Na, NaNO2 and B 744-99 were studied simultaneously on length and on cGMP-levels in isolated circular strips of bovine coronary arteries. 1. All 4 nitro-compounds concentration dependently relaxed the strips in close association with pronounced increases in cGMP-levels which preceded the mechanical responses. 2. The relaxant effects of all 4 nitro-compounds were significantly potentiated by the predominant inhibitor of cGMP-hydrolysis M & B 22,948, which also potentiated the increase in cGMP-levels of the two nitro-compounds in which it was studied (nitroglycerin and nitroprusside-Na). 3. Non-substituted cGMP and -- much stronger -- its 8 bromo-derivative also relaxed the strips and these effects were likewise potentiated by M & B 22,948. 4. When the log increase in cGMP produced by the 4 nitro-compounds were plotted against percent relaxation (probit scale) a linear and highly significant positive correlation was obtained. 5. The results provide evidence that the increases in cGMP caused by the 4 nitro-compounds studied are responsible for the smooth muscle relaxing actions of these drugs."}
{"id": "PMID:231209", "title": "Possible subdivision of postsynaptic alpha-adrenoceptors mediating pressor responses in the pithed rat.", "content": "Additional evidence has been obtained indicating a possible subclassification of postsynaptic alpha-adrenoceptors into alpha 1 - and alpha 2 -subtypes. The pressor responses to the alpha-adrenoceptor agonists L-phenylephrine and guanfacine were quantified after i.v. administration to pithed rats. The alpha-sympatholytic drug yohimbine (1 mg/kg) displaced both dose-response curves to the right, but the effect was greatest for guanfacine. After prazosin (0.1 mg/kg) a 53-fold shift to the right was noticed for the dose-response characteristic of L-phenylephrine. Prazosin antagonized the effect of only the higher doses of guanfacine. The findings indicate that L-phenylephrine and prazosin preferentially interact with alpha 1 -adrenoceptors as agonist and antagonist, respectively. Yohimbine proved less selective than prazosin, but preferentially blocks postjunctional alpha 2 -adrenoceptors in the vascular wall. The results obtained with guanfacine may be interpreted to indicate that this drug acts on alpha 2 -adrenoceptors at lower doses and additionally stimulates alpha 1 -adrenoceptors at higher ones. Preliminary findings with corynanthine and rauwolscine support this interpretation.", "contents": "Possible subdivision of postsynaptic alpha-adrenoceptors mediating pressor responses in the pithed rat. Additional evidence has been obtained indicating a possible subclassification of postsynaptic alpha-adrenoceptors into alpha 1 - and alpha 2 -subtypes. The pressor responses to the alpha-adrenoceptor agonists L-phenylephrine and guanfacine were quantified after i.v. administration to pithed rats. The alpha-sympatholytic drug yohimbine (1 mg/kg) displaced both dose-response curves to the right, but the effect was greatest for guanfacine. After prazosin (0.1 mg/kg) a 53-fold shift to the right was noticed for the dose-response characteristic of L-phenylephrine. Prazosin antagonized the effect of only the higher doses of guanfacine. The findings indicate that L-phenylephrine and prazosin preferentially interact with alpha 1 -adrenoceptors as agonist and antagonist, respectively. Yohimbine proved less selective than prazosin, but preferentially blocks postjunctional alpha 2 -adrenoceptors in the vascular wall. The results obtained with guanfacine may be interpreted to indicate that this drug acts on alpha 2 -adrenoceptors at lower doses and additionally stimulates alpha 1 -adrenoceptors at higher ones. Preliminary findings with corynanthine and rauwolscine support this interpretation."}
{"id": "PMID:231210", "title": "Comparison of the cardiostimulatory effects of acetylcholine and nicotine on the working guinea-pig heart.", "content": "The isolated working guinea-pig heart was used to compare the cardiostimulatory effects of acetylcholine and nicotine observed in the presence of atropine. Both agonists increased aortic pressure, left ventricular pressure, left ventricular dP/dt, cardiac output, and ventricular cyclic AMP levels. These responses were qualitatively and quantitatively similar to the effects of exogenous norepinephrine. Hexamethonium treatment abolished the responses to acetylcholine and to nicotine. However, several differences in the responses of the two agonists were also observed with respect to: 1) the effect of propranolol pretreatment, 2) selective effects on coronary and aortic flow rates, 3) coefficients of correlation between ventricular cyclic AMP and changes in dP/dt, and 4) the \"autoinhibition\" effect. The results support the view that the cardiostimulatory effects of acetylcholine are due entirely to endogenous catecholamine release, but that the effects of nicotine may involve an additional action.", "contents": "Comparison of the cardiostimulatory effects of acetylcholine and nicotine on the working guinea-pig heart. The isolated working guinea-pig heart was used to compare the cardiostimulatory effects of acetylcholine and nicotine observed in the presence of atropine. Both agonists increased aortic pressure, left ventricular pressure, left ventricular dP/dt, cardiac output, and ventricular cyclic AMP levels. These responses were qualitatively and quantitatively similar to the effects of exogenous norepinephrine. Hexamethonium treatment abolished the responses to acetylcholine and to nicotine. However, several differences in the responses of the two agonists were also observed with respect to: 1) the effect of propranolol pretreatment, 2) selective effects on coronary and aortic flow rates, 3) coefficients of correlation between ventricular cyclic AMP and changes in dP/dt, and 4) the \"autoinhibition\" effect. The results support the view that the cardiostimulatory effects of acetylcholine are due entirely to endogenous catecholamine release, but that the effects of nicotine may involve an additional action."}
{"id": "PMID:231211", "title": "Virus-specific sequences in nuclear DNA from non-producer hamster Rous sarcoma.", "content": "Proviral DNA from non-producer Rous sarcoma in Syrian hamster contains practically all the nucleotide sequences presented in 125I-labeled RNA from Rous sarcoma virus, Carr-Zilber strain. Virus-specific sequences consist of moderately reiterated and unique DNA regions. The amount of Rous sarcoma virus-specific provirus equivalents in hamster Rous sarcoma DNA is equal to 5.2 +/- 0.01. Experiments on transfection show that proviral DNA studied possesses biological activity in respect to cell transformation and virus production. The infectivity of DNA from hamster tumor does not depend on the expression of group-specific (gs) antigen in the recipient cells.", "contents": "Virus-specific sequences in nuclear DNA from non-producer hamster Rous sarcoma. Proviral DNA from non-producer Rous sarcoma in Syrian hamster contains practically all the nucleotide sequences presented in 125I-labeled RNA from Rous sarcoma virus, Carr-Zilber strain. Virus-specific sequences consist of moderately reiterated and unique DNA regions. The amount of Rous sarcoma virus-specific provirus equivalents in hamster Rous sarcoma DNA is equal to 5.2 +/- 0.01. Experiments on transfection show that proviral DNA studied possesses biological activity in respect to cell transformation and virus production. The infectivity of DNA from hamster tumor does not depend on the expression of group-specific (gs) antigen in the recipient cells."}
{"id": "PMID:231212", "title": "Peripheral blood lymphocytes and EAC-rosette forming cells in B77 tumor bearing rats.", "content": "The percentage and absolute numbers of peripheral blood lymphocytes and EAC-rosette forming cells were evaluated in B77 tumor bearing rats. The peripheral blood lymphocytes were in high level even in rats bearing very small tumors; this result suggest the mobilization of lymphoyctes into peripheral blood in tumor bearing rats. The increase of EAC-rosette forming cells was accompanied with the growth of tumors.", "contents": "Peripheral blood lymphocytes and EAC-rosette forming cells in B77 tumor bearing rats. The percentage and absolute numbers of peripheral blood lymphocytes and EAC-rosette forming cells were evaluated in B77 tumor bearing rats. The peripheral blood lymphocytes were in high level even in rats bearing very small tumors; this result suggest the mobilization of lymphoyctes into peripheral blood in tumor bearing rats. The increase of EAC-rosette forming cells was accompanied with the growth of tumors."}
{"id": "PMID:231213", "title": "Blocking factor in sera of MC1 and B77 tumor bearing rats detected by LAI assay.", "content": "A modified form of the leukocyte adherence inhibition assay (LAI assay) has been used to detect the blocking factor in serum of the Lewis (LW) inbred rats and the F1 hybrids of the inbred LW X AVN strains with transplantated syngeneic B77 and MC1 tumors. This study has indicated that the cell mediated antitumor immune response of rats immunized with living tumor cells and the blocking factor in serum of rats with progressively growing tumors may be demonstrated by the LAI assay with incubation time prolonged to 20 hr (LAI assay-IT20). In addition, the specificity of the blocking effect and the disappearance of blocking factor after surgical removal of tumors have also been demonstrated in this paper.", "contents": "Blocking factor in sera of MC1 and B77 tumor bearing rats detected by LAI assay. A modified form of the leukocyte adherence inhibition assay (LAI assay) has been used to detect the blocking factor in serum of the Lewis (LW) inbred rats and the F1 hybrids of the inbred LW X AVN strains with transplantated syngeneic B77 and MC1 tumors. This study has indicated that the cell mediated antitumor immune response of rats immunized with living tumor cells and the blocking factor in serum of rats with progressively growing tumors may be demonstrated by the LAI assay with incubation time prolonged to 20 hr (LAI assay-IT20). In addition, the specificity of the blocking effect and the disappearance of blocking factor after surgical removal of tumors have also been demonstrated in this paper."}
{"id": "PMID:231214", "title": "[Intraventricular hemorrhage with hepatic insufficiency--report of a case (author's transl)].", "content": "Authors report a case of intraventricular hemorrhage with hepatic insufficiency. A 36-year-old man was admitted following the sudden onset of coma. For 10 years before admission he had suffered general fatigue and jaundice, which were treated with medication as acute hepatitis. On the day of admission he began to suffer from a severe headache. Within one hour he was comatose and began to have vomiting, followed by seizures characterized by tonic movement of the right extremities. Lumbar puncture showed an initial pressure over 400 mmH2O, with grossly bloody spinal fluid. Numerous hemorrhages were noted in both optic fundi. Bilateral carotid angiography demonstrated slight enlargement of left lateral ventricle. Computerized tomography revealed that the lareral, third and fourth ventricles were dilated. There were discrete areas of increased absorption coefficient with values measuring between 30 to 35 in the Hounsfield scale in all ventricles. Two burr holes in both frontal areas were performed. About 50ml of blood clot at left ventricle and 30 ml of blood clot with liquor at right ventricle were removed. The patient died 7 days after operation. Autopsy revealed clotted blood in the whole ventricular system, mainly in right anterior horn of lateral ventricle, and a markedly cirrhotic liver with hepatoma. In our review of the literature, the relationship between intraventricular hemorrhage and bleeding tendency caused by hepatic insufficiency was discussed.", "contents": "[Intraventricular hemorrhage with hepatic insufficiency--report of a case (author's transl)]. Authors report a case of intraventricular hemorrhage with hepatic insufficiency. A 36-year-old man was admitted following the sudden onset of coma. For 10 years before admission he had suffered general fatigue and jaundice, which were treated with medication as acute hepatitis. On the day of admission he began to suffer from a severe headache. Within one hour he was comatose and began to have vomiting, followed by seizures characterized by tonic movement of the right extremities. Lumbar puncture showed an initial pressure over 400 mmH2O, with grossly bloody spinal fluid. Numerous hemorrhages were noted in both optic fundi. Bilateral carotid angiography demonstrated slight enlargement of left lateral ventricle. Computerized tomography revealed that the lareral, third and fourth ventricles were dilated. There were discrete areas of increased absorption coefficient with values measuring between 30 to 35 in the Hounsfield scale in all ventricles. Two burr holes in both frontal areas were performed. About 50ml of blood clot at left ventricle and 30 ml of blood clot with liquor at right ventricle were removed. The patient died 7 days after operation. Autopsy revealed clotted blood in the whole ventricular system, mainly in right anterior horn of lateral ventricle, and a markedly cirrhotic liver with hepatoma. In our review of the literature, the relationship between intraventricular hemorrhage and bleeding tendency caused by hepatic insufficiency was discussed."}
{"id": "PMID:231223", "title": "Ultrastructural observations on intercellular contacts of nigral dendrites.", "content": "Possible morphological correlates of dendritic release sites for dopamine have been investigated in the rat substantia nigra. Electronmicroscopic and freeze etching studies show that nigral dendrites fail to form dendrodendritic contacts but on the contrary are always separated by glial elements, which in turn are connected by multiple gap junctions. No dendro-axonic synapses are present but large specialized symmetrical junctions could provide a possible morphological specialization for a dopamine transfer from presynaptic dendrites to axon endings.", "contents": "Ultrastructural observations on intercellular contacts of nigral dendrites. Possible morphological correlates of dendritic release sites for dopamine have been investigated in the rat substantia nigra. Electronmicroscopic and freeze etching studies show that nigral dendrites fail to form dendrodendritic contacts but on the contrary are always separated by glial elements, which in turn are connected by multiple gap junctions. No dendro-axonic synapses are present but large specialized symmetrical junctions could provide a possible morphological specialization for a dopamine transfer from presynaptic dendrites to axon endings."}
{"id": "PMID:231224", "title": "Cyclic GMP and cyclic AMP levels in median eminence, hypothalamus and pituitary gland of the rat after decapitation or microwave irradiation.", "content": "Cyclic AMP and cyclic GMP content of the median eminence (ME), medial basal hypothalamus (MBH), posterior pituitary (PP) and anterior pituitary (AP) of inact male rats was measured by radioimmunoassay following decapitation or exposure to microwave irradiation (MW). Levels of both nucleotides in MW irradiated animals were higher in all three nervous tissues studied than in the AP. Following decapitation cyclic AMP levels increased strikingly in the MBH and ME, slightly in the AP, but remained unchanged in the PP. Cyclic GMP levels increased more markedly in the ME than in the MBH, slightly in the PP and did not change in the AP. The distinct synthesizing capability of the cyclic AMP and cyclic GMP generating systems in the ME, a region rich in neurohormones known to control anterior pituitary function, raises the possibility that these nucleotides are involved in the process of neurohormone secretion by the ME.", "contents": "Cyclic GMP and cyclic AMP levels in median eminence, hypothalamus and pituitary gland of the rat after decapitation or microwave irradiation. Cyclic AMP and cyclic GMP content of the median eminence (ME), medial basal hypothalamus (MBH), posterior pituitary (PP) and anterior pituitary (AP) of inact male rats was measured by radioimmunoassay following decapitation or exposure to microwave irradiation (MW). Levels of both nucleotides in MW irradiated animals were higher in all three nervous tissues studied than in the AP. Following decapitation cyclic AMP levels increased strikingly in the MBH and ME, slightly in the AP, but remained unchanged in the PP. Cyclic GMP levels increased more markedly in the ME than in the MBH, slightly in the PP and did not change in the AP. The distinct synthesizing capability of the cyclic AMP and cyclic GMP generating systems in the ME, a region rich in neurohormones known to control anterior pituitary function, raises the possibility that these nucleotides are involved in the process of neurohormone secretion by the ME."}
{"id": "PMID:231225", "title": "Elimination of paradoxical sleep by lesions of the pontine gigantocellular tegmental field in the cat.", "content": "Bilateral lesions of the pontine gigantocellular tegmental field in the cat resulted in the complete elimination of paradoxical sleep during 3 weeks postoperative recording. The tonic muscular atonia, normally characteristic of this state, was absent. The phasic components, rapid eye movements and ponto-geniculooccipital (PGO) spikes, did not occur in association with an activated EEG, as they normally do in paradoxical sleep. In fact, PGO spikes were virtually absent immediately after the lesion and were only secondarily apparent as isolated phenomena during slow wave sleep to represent in total daily number 5% of normal the first week and 15% of normal the third week after the lesion. These results indicate that neurons whose perikarya and/or processes are located within the pontine gigantocellular tegmental field and which are not part of the noradrenaline locus coeruleus complex, are critical for paradoxical sleep.", "contents": "Elimination of paradoxical sleep by lesions of the pontine gigantocellular tegmental field in the cat. Bilateral lesions of the pontine gigantocellular tegmental field in the cat resulted in the complete elimination of paradoxical sleep during 3 weeks postoperative recording. The tonic muscular atonia, normally characteristic of this state, was absent. The phasic components, rapid eye movements and ponto-geniculooccipital (PGO) spikes, did not occur in association with an activated EEG, as they normally do in paradoxical sleep. In fact, PGO spikes were virtually absent immediately after the lesion and were only secondarily apparent as isolated phenomena during slow wave sleep to represent in total daily number 5% of normal the first week and 15% of normal the third week after the lesion. These results indicate that neurons whose perikarya and/or processes are located within the pontine gigantocellular tegmental field and which are not part of the noradrenaline locus coeruleus complex, are critical for paradoxical sleep."}
{"id": "PMID:231226", "title": "5'-triphosphate recycles independently of acetylcholine in cholinergic synaptic vesicles.", "content": "The effect of hemicholinium-3 (HC-3) on vesicular contents in acetylcholine (ACh) and 5-triphosphate (ATP) and the vesicular incorporation of 14C-label derived from [14C]choline ,nd 3H-label derived from [3H]adenosine was investigated after low frequency stimulation (with a subsequent rest period) of the Torpedo electric organ. HC-3 (100 microM) caused an increased depletion of vesicular ACh and blocked the incorporation of 14C-label whereas contents in vesicular ATP and 3H-incorporation were identical with and without HC-3. HC-3 also blocked the recovery of electrical response of the tissue after stimulation but did not cause a change in vesicle numbers. The result suggest that synaptic vesicles continue to recycle ATP in the absence of recycling of ACh and that vesicular uptake and storage of the two components are not coupled to each other.", "contents": "5'-triphosphate recycles independently of acetylcholine in cholinergic synaptic vesicles. The effect of hemicholinium-3 (HC-3) on vesicular contents in acetylcholine (ACh) and 5-triphosphate (ATP) and the vesicular incorporation of 14C-label derived from [14C]choline ,nd 3H-label derived from [3H]adenosine was investigated after low frequency stimulation (with a subsequent rest period) of the Torpedo electric organ. HC-3 (100 microM) caused an increased depletion of vesicular ACh and blocked the incorporation of 14C-label whereas contents in vesicular ATP and 3H-incorporation were identical with and without HC-3. HC-3 also blocked the recovery of electrical response of the tissue after stimulation but did not cause a change in vesicle numbers. The result suggest that synaptic vesicles continue to recycle ATP in the absence of recycling of ACh and that vesicular uptake and storage of the two components are not coupled to each other."}
{"id": "PMID:231227", "title": "Pharmacology of (+)- and (-)-baclofen: GABA-dependant rotational behaviour and [3H]GABA receptor binding studies.", "content": "(+)- and (-)-baclofen were equiactive in inducing contralateral rotational behaviour following their unilateral injection into the zona reticulata of the rat substantia nigra, a proposed GABA-dependent rotational behaviour model, and in displacing the specific binding of [3H]GABA to frozen and thawed membrane preparations of rat brain. These non-stereospecific actions of baclofen at a population of cerebral GABA receptors contrast with stereospecific neuronal depressant effects probably mediated via presynaptic inhibition of the release of excitatory amino acid neurotransmitters. The present results indicate that baclofen may have two distinct mechanisms of action and this may account for the debate on the pharmacology of this compound.", "contents": "Pharmacology of (+)- and (-)-baclofen: GABA-dependant rotational behaviour and [3H]GABA receptor binding studies. (+)- and (-)-baclofen were equiactive in inducing contralateral rotational behaviour following their unilateral injection into the zona reticulata of the rat substantia nigra, a proposed GABA-dependent rotational behaviour model, and in displacing the specific binding of [3H]GABA to frozen and thawed membrane preparations of rat brain. These non-stereospecific actions of baclofen at a population of cerebral GABA receptors contrast with stereospecific neuronal depressant effects probably mediated via presynaptic inhibition of the release of excitatory amino acid neurotransmitters. The present results indicate that baclofen may have two distinct mechanisms of action and this may account for the debate on the pharmacology of this compound."}
{"id": "PMID:231228", "title": "Bromocriptine and lisuride stimulate the accumulation of cyclic AMP in intact slices but not in homogenates of rat neostriatum.", "content": "The effects of bromocriptine and lisuride on cyclic AMP concentrations in homogenates and in intact slices of rat neostriatum were investigated. Significant increases in cyclic AMP concentration were found after a 10-min exposure to bromocriptine and lisuride in striatal intact slices. On the contrary, as previously found, the two dopaminergic ergot derivatives did not stimulate dopamine-senstiive adenylate cyclase present in striatal homogenates. The stimulatory effects observed only in intact tissues were blocked by the specific dopamine receptor blocking agent fluphenazine. It is tempting to conclude that dopaminergic ergot derivatives have a site of action different from that stimulated by classic dopamine agonists in tissue homogenates.", "contents": "Bromocriptine and lisuride stimulate the accumulation of cyclic AMP in intact slices but not in homogenates of rat neostriatum. The effects of bromocriptine and lisuride on cyclic AMP concentrations in homogenates and in intact slices of rat neostriatum were investigated. Significant increases in cyclic AMP concentration were found after a 10-min exposure to bromocriptine and lisuride in striatal intact slices. On the contrary, as previously found, the two dopaminergic ergot derivatives did not stimulate dopamine-senstiive adenylate cyclase present in striatal homogenates. The stimulatory effects observed only in intact tissues were blocked by the specific dopamine receptor blocking agent fluphenazine. It is tempting to conclude that dopaminergic ergot derivatives have a site of action different from that stimulated by classic dopamine agonists in tissue homogenates."}
{"id": "PMID:231229", "title": "Parallel investigations of the effects of adenosine on evoked potentials and cyclic AMP accumulation in hippocampus slices of the rat.", "content": "In slices of rat hippocampus, adenosine and its receptor agonist, 2-chloro-adenosine, were both found to (a) enhance the intracellular accumulation of cyclic adenosine monophosphate (cAMP) and (b) depress neuronal evoked responses to electrical stimulation. The differences in the dose/effect curves for the biochemical and electrophysiological changes cast doubt on a causal relationship between the two effects.", "contents": "Parallel investigations of the effects of adenosine on evoked potentials and cyclic AMP accumulation in hippocampus slices of the rat. In slices of rat hippocampus, adenosine and its receptor agonist, 2-chloro-adenosine, were both found to (a) enhance the intracellular accumulation of cyclic adenosine monophosphate (cAMP) and (b) depress neuronal evoked responses to electrical stimulation. The differences in the dose/effect curves for the biochemical and electrophysiological changes cast doubt on a causal relationship between the two effects."}
{"id": "PMID:231230", "title": "Comparative study of the neuronal populations containing beta-endorphin, corticotropin and dopamine in the arcuate nucleus of the rat hypothalamus.", "content": "Neurons simultaneously immunoreactive with anti-beta-endorphin and anti-(17-39) corticotropin (anti(17-39) ACTH) have been detected in the arcuate and ventromedial nuclei of the hypothalamus of colchicine-treated rats. These neurons are different from those fluorescent with the Falck and Hillarp technique. These results show that in the arcuate nucleus, immunoreactive ACTH and beta-endorphine are stored in the same neurons which are different from dopamine-containing neurons.", "contents": "Comparative study of the neuronal populations containing beta-endorphin, corticotropin and dopamine in the arcuate nucleus of the rat hypothalamus. Neurons simultaneously immunoreactive with anti-beta-endorphin and anti-(17-39) corticotropin (anti(17-39) ACTH) have been detected in the arcuate and ventromedial nuclei of the hypothalamus of colchicine-treated rats. These neurons are different from those fluorescent with the Falck and Hillarp technique. These results show that in the arcuate nucleus, immunoreactive ACTH and beta-endorphine are stored in the same neurons which are different from dopamine-containing neurons."}
{"id": "PMID:231231", "title": "Inhibition of acetylcholine outflow from guinea-pig cerebral cortex following locus coeruleus stimulation.", "content": "Experiments were performed in unanaesthetized guinea-pigs in order to obtain direct evidence that the noradrenergic projections from locus coeruleus (L.C.) to cerebral cortex inhibit the acetylcholine (ACh) release. The animals were provided with left and right epidural cups, to collect outflowing ACh and with a stimulating electrode, positioned in the left L.C. The electrical stimulation of L.C. caused a significant reduction of ACh outflow from both parietal areas. This effect was abolished, reduced or prevented by phentolamine, phenoxybenzamine or reserpine plus alpha-mt pretreatment, hence showing to be alpha-mediated.", "contents": "Inhibition of acetylcholine outflow from guinea-pig cerebral cortex following locus coeruleus stimulation. Experiments were performed in unanaesthetized guinea-pigs in order to obtain direct evidence that the noradrenergic projections from locus coeruleus (L.C.) to cerebral cortex inhibit the acetylcholine (ACh) release. The animals were provided with left and right epidural cups, to collect outflowing ACh and with a stimulating electrode, positioned in the left L.C. The electrical stimulation of L.C. caused a significant reduction of ACh outflow from both parietal areas. This effect was abolished, reduced or prevented by phentolamine, phenoxybenzamine or reserpine plus alpha-mt pretreatment, hence showing to be alpha-mediated."}
{"id": "PMID:231232", "title": "High-affinity binding of [3H]muscimol to subcellular particles of a neurone-enriched culture of embryonic rat brain.", "content": "High-affinity, Na+-independent binding of [3H]muscimol (KB approximately equal to 1.6 x 10(-8) M; Bmax approximately equal to 0.14 nmol/g pellet) occurred to a frozen-thawed particulate fraction of 74-h-old neurone-enriched cultures prepared from the cerebra of 12-13-day-old rat embryos. This finding provides evidence that GABA-receptors exist on cultured neurones which contain only a few synaptic connections.", "contents": "High-affinity binding of [3H]muscimol to subcellular particles of a neurone-enriched culture of embryonic rat brain. High-affinity, Na+-independent binding of [3H]muscimol (KB approximately equal to 1.6 x 10(-8) M; Bmax approximately equal to 0.14 nmol/g pellet) occurred to a frozen-thawed particulate fraction of 74-h-old neurone-enriched cultures prepared from the cerebra of 12-13-day-old rat embryos. This finding provides evidence that GABA-receptors exist on cultured neurones which contain only a few synaptic connections."}
{"id": "PMID:231233", "title": "Kainate neurotoxicity and glutamate inactivation.", "content": "Dihydrokainate, an inhibitor of high affinity L-glutamate as an excitant of cat spinal neurones in vivo. This action of dihydrokainate was selective in that the effects of excitants taken up actively in vitro by CNS tissue (L-aspartate, D- and L-glutamate and L-homocysteate) were enhanced whereas those of other substances not taken up (acetylcholine, D-homocysteate, kainate and N-methyl-D-aspartate) were not. Since kainate and dihydrokainate have similar potencies as inhibitors of L-glutamate uptake, interference with the inactivation of synaptically released L-glutamate may contribute to the neurotoxic effects of kainate.", "contents": "Kainate neurotoxicity and glutamate inactivation. Dihydrokainate, an inhibitor of high affinity L-glutamate as an excitant of cat spinal neurones in vivo. This action of dihydrokainate was selective in that the effects of excitants taken up actively in vitro by CNS tissue (L-aspartate, D- and L-glutamate and L-homocysteate) were enhanced whereas those of other substances not taken up (acetylcholine, D-homocysteate, kainate and N-methyl-D-aspartate) were not. Since kainate and dihydrokainate have similar potencies as inhibitors of L-glutamate uptake, interference with the inactivation of synaptically released L-glutamate may contribute to the neurotoxic effects of kainate."}
{"id": "PMID:231236", "title": "Morphine presynaptically inhibits a ganglionic cholinergic synapse.", "content": "The effects of morphine on synaptic transmission through the inferior mesenteric ganglion (IMG) were studied using intracellular recording techniques. Morphine produced a reversible, dose-dependent reduction in the quantal content of the synaptic potentials with little or no effect on quantal size or the properties of the ganglion cells. This effect of morphine was antagonized by naloxone suggesting the presence of specific preganglionic opiate receptors.", "contents": "Morphine presynaptically inhibits a ganglionic cholinergic synapse. The effects of morphine on synaptic transmission through the inferior mesenteric ganglion (IMG) were studied using intracellular recording techniques. Morphine produced a reversible, dose-dependent reduction in the quantal content of the synaptic potentials with little or no effect on quantal size or the properties of the ganglion cells. This effect of morphine was antagonized by naloxone suggesting the presence of specific preganglionic opiate receptors."}
{"id": "PMID:231237", "title": "Respiratory neurons of the pneumotaxic center during sleep and wakefulness.", "content": "Extracellular recordings were made from respiratory related units (RRUs) in the pneumotaxic center (PNC) of unanesthetized cats across states of consciousness: wakefulness, NREM and REM sleep. Contrary to expectations from results in acute preparations, well-modulated respiratory activity was detected in chronic animals with vagi intact. Pontine RRU activity decreased during sleep in 75% of the cells studied. The greatest reduction occurred during REM sleep.", "contents": "Respiratory neurons of the pneumotaxic center during sleep and wakefulness. Extracellular recordings were made from respiratory related units (RRUs) in the pneumotaxic center (PNC) of unanesthetized cats across states of consciousness: wakefulness, NREM and REM sleep. Contrary to expectations from results in acute preparations, well-modulated respiratory activity was detected in chronic animals with vagi intact. Pontine RRU activity decreased during sleep in 75% of the cells studied. The greatest reduction occurred during REM sleep."}
{"id": "PMID:231238", "title": "Specificity of opioids towards the mu-, delta- and epsilon-opiate receptors.", "content": "The potency of a number of opioid agonists have been determined on three different bioassays, the isolated guinea-pig ileum (GPI), the mouse vas deferens (MVD) and the rat vas deferens (RVD). With the exception of beta-endorphin, compounds with opioid activity on the GPI and the MVD exhibited considerably less or no activity on the RVD; the opiate receptor in this latter tissue being thus characterized as beta-endorphin selective ('epsilon-receptor'). A system of classification of opioids according to their relative relative affinities for particular opiate receptor types is given.", "contents": "Specificity of opioids towards the mu-, delta- and epsilon-opiate receptors. The potency of a number of opioid agonists have been determined on three different bioassays, the isolated guinea-pig ileum (GPI), the mouse vas deferens (MVD) and the rat vas deferens (RVD). With the exception of beta-endorphin, compounds with opioid activity on the GPI and the MVD exhibited considerably less or no activity on the RVD; the opiate receptor in this latter tissue being thus characterized as beta-endorphin selective ('epsilon-receptor'). A system of classification of opioids according to their relative relative affinities for particular opiate receptor types is given."}
{"id": "PMID:231239", "title": "Synaptic responses of reticulospinal neurons in the cat: spinal cord dorsal funiculi are an effective source.", "content": "Stimulation of spinal cord dorsal funiculi (DF), as compared with stimulation of ventrolateral fascicle (VLF) in which the spinoreticular pathways are located, activated a higher percentage of reticulospinal (RS) neurons (95% vs. 75%). Polysynaptic EPSPs evoked from DF at C2 segment had shorter latency (10.1 msec +/- vs. VLF C2-13.2 msec +/- 0.9-mean +/- S.E.M.). When the intensity of stimulation was close to threshold (1.5 T), EPSPs from DF had steeper slopes on the increasing phase and were of longer duration. Threshold for setting up of synaptic activity from DF at the majority of observed RS neurons was low; recording of antidromic responses in hindlimb nerves showed that fast-conducting myelinized afferents were activated. The functional connection between DF and RS systems may participate in prompt and generalized reflex reactions.", "contents": "Synaptic responses of reticulospinal neurons in the cat: spinal cord dorsal funiculi are an effective source. Stimulation of spinal cord dorsal funiculi (DF), as compared with stimulation of ventrolateral fascicle (VLF) in which the spinoreticular pathways are located, activated a higher percentage of reticulospinal (RS) neurons (95% vs. 75%). Polysynaptic EPSPs evoked from DF at C2 segment had shorter latency (10.1 msec +/- vs. VLF C2-13.2 msec +/- 0.9-mean +/- S.E.M.). When the intensity of stimulation was close to threshold (1.5 T), EPSPs from DF had steeper slopes on the increasing phase and were of longer duration. Threshold for setting up of synaptic activity from DF at the majority of observed RS neurons was low; recording of antidromic responses in hindlimb nerves showed that fast-conducting myelinized afferents were activated. The functional connection between DF and RS systems may participate in prompt and generalized reflex reactions."}
{"id": "PMID:231240", "title": "Intrahippocampal injections of ibotenic acid provide histological evidence for a neurotoxic mechanism different from kainic acid.", "content": "Stereotaxic injections of ibotenic acid (IBO) and kainic acid (KA) into either the dorsal hippocampus or the lateral cerebroventricle were performed in order to determine the relative potencies of the drugs and the vulnerability of different hippocampal cell types to their neurotoxic action, IBO was found to be approximately five times less potent than KA in causing degeneration of hippocampal neuronal cell bodies. Unlike KA (0.5 and 1.0 microgram), IBO (5.0 micrograms) caused few signs of intrahippocampal bleeding or necrosis of non-neuronal elements. Pyramidal cells of the CA3 and CA4 regions were the most sensitive and dentate granule cells the least sensitive to KA. In contrast, IBO cused degeneration of granule cells and CA3/CA4 pyramids to an equal extent.", "contents": "Intrahippocampal injections of ibotenic acid provide histological evidence for a neurotoxic mechanism different from kainic acid. Stereotaxic injections of ibotenic acid (IBO) and kainic acid (KA) into either the dorsal hippocampus or the lateral cerebroventricle were performed in order to determine the relative potencies of the drugs and the vulnerability of different hippocampal cell types to their neurotoxic action, IBO was found to be approximately five times less potent than KA in causing degeneration of hippocampal neuronal cell bodies. Unlike KA (0.5 and 1.0 microgram), IBO (5.0 micrograms) caused few signs of intrahippocampal bleeding or necrosis of non-neuronal elements. Pyramidal cells of the CA3 and CA4 regions were the most sensitive and dentate granule cells the least sensitive to KA. In contrast, IBO cused degeneration of granule cells and CA3/CA4 pyramids to an equal extent."}
{"id": "PMID:231241", "title": "Naloxone potentiation of 2-Br-alpha-ergocryptine (CB 154) effects on GH secretion in man.", "content": "The effect of the combined administration of either CB 154 (2.5 mg/osM) or L-DOPA (500 mg/osM) and naloxone have been studied in six normal male volunteers. Naloxone cause a clear-cut potentiation of CB 154 effects on human growth hormone (hGH) secretion and only a slight, statistically non-significant, potentiation of L-DOPA effects on hGH secretion. These results have been discussed in the light of morphofunctional findings showing possible interactions between dopamine (DA) systems and somatostatin-positive and enkephalin-positive nerve terminals.", "contents": "Naloxone potentiation of 2-Br-alpha-ergocryptine (CB 154) effects on GH secretion in man. The effect of the combined administration of either CB 154 (2.5 mg/osM) or L-DOPA (500 mg/osM) and naloxone have been studied in six normal male volunteers. Naloxone cause a clear-cut potentiation of CB 154 effects on human growth hormone (hGH) secretion and only a slight, statistically non-significant, potentiation of L-DOPA effects on hGH secretion. These results have been discussed in the light of morphofunctional findings showing possible interactions between dopamine (DA) systems and somatostatin-positive and enkephalin-positive nerve terminals."}
{"id": "PMID:231242", "title": "Adenosine 3':5'-monophosphate-dependent in vitro phosphorylation of synaptosomal membrane proteins from rat corpus striatum following systemic administration of L-DOPA and bromocriptine.", "content": "In vitro phosphorylation of synaptosomal membrane preparation from rat striata was stimulated by addition of 5 microM cAMP, Administration of L-DOPA to rats treated previously with an L-amino acid decarboxylase inhibitor, or administration of bromocriptine resulted in a marked decrease in the in vitro phosphorylation presumably by increasing endogenous cAMP levels and thereby stimulating endogenous protein phosphorylation.", "contents": "Adenosine 3':5'-monophosphate-dependent in vitro phosphorylation of synaptosomal membrane proteins from rat corpus striatum following systemic administration of L-DOPA and bromocriptine. In vitro phosphorylation of synaptosomal membrane preparation from rat striata was stimulated by addition of 5 microM cAMP, Administration of L-DOPA to rats treated previously with an L-amino acid decarboxylase inhibitor, or administration of bromocriptine resulted in a marked decrease in the in vitro phosphorylation presumably by increasing endogenous cAMP levels and thereby stimulating endogenous protein phosphorylation."}
{"id": "PMID:231243", "title": "Diurnal changes in melatonin binding sites of hamster and rat brains. Correlations with neuroendocrine responsiveness to melatonin.", "content": "A diurnal variation in neuroendocrine sensitivity to melatonin is known to occur in hamsters and rats. The present experiments were carried out to examine the possibility that affinity and/or number of melatonin binding sites in brain could change accordingly at the two times when exogenous melatonin is known to be ineffective or effective to produce neuroendocrine changes, i.e., at 07 : 00 or 20 : 00 h (lights on from 07 : 00 to 21 : 00 h daily). The number of melatonin binding sites in hamster and rat brains was at 20 : 00 h 34--56% higher than at 07 : 00 h, without changing their affinity towards [3H]melatonin (hamster: Kd = 53 nM; rat: Kd = 73--77 nM). These alterations in melatonin receptor density may play a role in daily changes in sensitivity to the exogenous methoxyindole.", "contents": "Diurnal changes in melatonin binding sites of hamster and rat brains. Correlations with neuroendocrine responsiveness to melatonin. A diurnal variation in neuroendocrine sensitivity to melatonin is known to occur in hamsters and rats. The present experiments were carried out to examine the possibility that affinity and/or number of melatonin binding sites in brain could change accordingly at the two times when exogenous melatonin is known to be ineffective or effective to produce neuroendocrine changes, i.e., at 07 : 00 or 20 : 00 h (lights on from 07 : 00 to 21 : 00 h daily). The number of melatonin binding sites in hamster and rat brains was at 20 : 00 h 34--56% higher than at 07 : 00 h, without changing their affinity towards [3H]melatonin (hamster: Kd = 53 nM; rat: Kd = 73--77 nM). These alterations in melatonin receptor density may play a role in daily changes in sensitivity to the exogenous methoxyindole."}
{"id": "PMID:231244", "title": "Opposite turning effects of dainic and ibotenic acid injected in the rat substantia nigra.", "content": "Unilateral intranigral administration of kainic and ibotenic acid, two putative stimulants of glutamatergic mechanisms, elicited turning behaviour starting from doses of 10 ng. While the turning produced by kainic acid was ipsilateral, that produced by ibotenic acid was contralateral to the injected side. Previous destruction of dopaminergic neurons on the side of the intranigral injection failed to reduce the turning behaviour. Peripheral treatment with picrotoxin did not reduce the turning in response to ibotenic acid. The results might suggest the existence of excitatory and inhibitory glutamate receptors which control nigral non-dopaminergic neurons mediating turning-behaviour.", "contents": "Opposite turning effects of dainic and ibotenic acid injected in the rat substantia nigra. Unilateral intranigral administration of kainic and ibotenic acid, two putative stimulants of glutamatergic mechanisms, elicited turning behaviour starting from doses of 10 ng. While the turning produced by kainic acid was ipsilateral, that produced by ibotenic acid was contralateral to the injected side. Previous destruction of dopaminergic neurons on the side of the intranigral injection failed to reduce the turning behaviour. Peripheral treatment with picrotoxin did not reduce the turning in response to ibotenic acid. The results might suggest the existence of excitatory and inhibitory glutamate receptors which control nigral non-dopaminergic neurons mediating turning-behaviour."}
{"id": "PMID:231245", "title": "Methods for rapid detection of human ocular viral infections.", "content": "Recent methods for detection of viruses in clinical specimens include immunofluorescence, immunoperoxidase, immune adherence hemagglutination, radioimmunoassay, enzyme-linked immunosorbent assay (ELISA), and immunoelectron microscopy. Some are useful for the detection of traces of viral antigens but are more complicated and time-consuming than others. Simple techniques of immunofluorescence and negative stain electron microscopy are used for the rapid detection of viruses in human adenoviral, herpetic, rubella, molluscum contagiosum, and vaccinial infections.", "contents": "Methods for rapid detection of human ocular viral infections. Recent methods for detection of viruses in clinical specimens include immunofluorescence, immunoperoxidase, immune adherence hemagglutination, radioimmunoassay, enzyme-linked immunosorbent assay (ELISA), and immunoelectron microscopy. Some are useful for the detection of traces of viral antigens but are more complicated and time-consuming than others. Simple techniques of immunofluorescence and negative stain electron microscopy are used for the rapid detection of viruses in human adenoviral, herpetic, rubella, molluscum contagiosum, and vaccinial infections."}
{"id": "PMID:231250", "title": "Low-calcium/high-phosphorus rickets in rats. II. Osteoclast changes.", "content": "Weanling rats were given a low Ca (0.003%)/high P (0.64%) diet with and without vitamin D for periods up to 6 weeks. An ultrastructural examination of selected areas of the proximal tibial metaphysis was carried out to study osteoclasts and their relation to calcified and uncalcified bone tissue. Osteoclasts were seen with ruffled borders adjacent to unmineralized osteoid or with their processes penetrating small patches of calcified osteoid tissue. In both cases the calcified bone margin had a 'frayed edge', suggesting that osteoclasts are capable of chemical demineralization, as well as phagocytic action. In a few cases, osteoblasts were seen adjoining osteoid seams with underlying calcified bone exhibiting frayed edges indicative of demineralization. Osteoclastic intranuclear inclusion bodies similar to those found in experimental lead poisoning were observed. It was considered that the presence of a frayed, calcified bone margin at a considerable distance from the osteoclast supports the proposition that the initial action of this cell is to demineralize calcified bone.", "contents": "Low-calcium/high-phosphorus rickets in rats. II. Osteoclast changes. Weanling rats were given a low Ca (0.003%)/high P (0.64%) diet with and without vitamin D for periods up to 6 weeks. An ultrastructural examination of selected areas of the proximal tibial metaphysis was carried out to study osteoclasts and their relation to calcified and uncalcified bone tissue. Osteoclasts were seen with ruffled borders adjacent to unmineralized osteoid or with their processes penetrating small patches of calcified osteoid tissue. In both cases the calcified bone margin had a 'frayed edge', suggesting that osteoclasts are capable of chemical demineralization, as well as phagocytic action. In a few cases, osteoblasts were seen adjoining osteoid seams with underlying calcified bone exhibiting frayed edges indicative of demineralization. Osteoclastic intranuclear inclusion bodies similar to those found in experimental lead poisoning were observed. It was considered that the presence of a frayed, calcified bone margin at a considerable distance from the osteoclast supports the proposition that the initial action of this cell is to demineralize calcified bone."}
{"id": "PMID:231248", "title": "Differential diagnosis of superficial ulcerations of the oral mucosa.", "content": "Superficial ulcerations of the oral mucosa often present a diagnostic challenge to the physician because of the similarity of one ulcer to another. A diagnosis is made by the analysis of multple factors, including the lesion's location, size, grouping, onset, patient's age, involvement of other systems of the body, and course of the disease. The histopathology of the lesion may be specific, especially in certain potentially fatal diseases. This paper presents the means for the differential diagnosis of a variety of superficial ulcers of the oral mucosa: varicella, herpangina, recurrent aphthous stomatitis, Beh\u00e7et's disease, Stevens-Johnson syndrome, traumatic ulcer, verrucous carcinoma, primary herpetic gingivostomatitis, recurrent herpetic stomatitis, pemphigus vulgaris, and benign mucous membrane pemphigoid.", "contents": "Differential diagnosis of superficial ulcerations of the oral mucosa. Superficial ulcerations of the oral mucosa often present a diagnostic challenge to the physician because of the similarity of one ulcer to another. A diagnosis is made by the analysis of multple factors, including the lesion's location, size, grouping, onset, patient's age, involvement of other systems of the body, and course of the disease. The histopathology of the lesion may be specific, especially in certain potentially fatal diseases. This paper presents the means for the differential diagnosis of a variety of superficial ulcers of the oral mucosa: varicella, herpangina, recurrent aphthous stomatitis, Beh\u00e7et's disease, Stevens-Johnson syndrome, traumatic ulcer, verrucous carcinoma, primary herpetic gingivostomatitis, recurrent herpetic stomatitis, pemphigus vulgaris, and benign mucous membrane pemphigoid."}
{"id": "PMID:231249", "title": "Granular cell tumors of the larynx.", "content": "Granular cell tumors of the larynx are uncommon lesions. Only 15 were identified at the Columbia-Presbyterian Medical Center, New York, during the past 45 years. These tumors produce hoarseness usually and are identified as small keratotic, polypoid, or sessile nodules involving the glottic region (most often posterior glottis, arytenoid, or vocal process). These lesions can usually satisfactorily be treated by endoscopic excision. On histologic examination, pseudoepitheliomatous hyperplasia is frequently seen and may be misinterpreted as squamous cell carcinoma.", "contents": "Granular cell tumors of the larynx. Granular cell tumors of the larynx are uncommon lesions. Only 15 were identified at the Columbia-Presbyterian Medical Center, New York, during the past 45 years. These tumors produce hoarseness usually and are identified as small keratotic, polypoid, or sessile nodules involving the glottic region (most often posterior glottis, arytenoid, or vocal process). These lesions can usually satisfactorily be treated by endoscopic excision. On histologic examination, pseudoepitheliomatous hyperplasia is frequently seen and may be misinterpreted as squamous cell carcinoma."}
{"id": "PMID:231251", "title": "Linguistic organization and cognitive implications of REM and NREM sleep-related reports.", "content": "Verbal reports related to REM and NREM sleep were subjected to syntactic (taking Chomskian standard theory as model) and pragmatic analysis (pause distribution within and between kernel sentences). Both in REM and NREM-verbal reports descriptions of the mental experience during sleep were syntactically correct and indicated little difficulty in lexical choice and little emotion. Even though the strategy appears to be the same (sequential) in both cases, the retrieval of content appears to be more difficult after NREM than after REM sleep. Perhaps different degrees of content consolidation in memory occur during the two types of sleep.", "contents": "Linguistic organization and cognitive implications of REM and NREM sleep-related reports. Verbal reports related to REM and NREM sleep were subjected to syntactic (taking Chomskian standard theory as model) and pragmatic analysis (pause distribution within and between kernel sentences). Both in REM and NREM-verbal reports descriptions of the mental experience during sleep were syntactically correct and indicated little difficulty in lexical choice and little emotion. Even though the strategy appears to be the same (sequential) in both cases, the retrieval of content appears to be more difficult after NREM than after REM sleep. Perhaps different degrees of content consolidation in memory occur during the two types of sleep."}
{"id": "PMID:231257", "title": "Effect of selection for high egg production in chickens on shedding of lymphoid leukosis virus and gs antigen into eggs.", "content": "Lymphoid leukosis virus (LLV) and group specific (gs) viral antigen were detected less frequently in albumen of eggs from two strains of Single Comb White Leghorns that had been selected for high egg production than in corresponding random-bred control strains, which represented the original base population. In a third selected strain, for which no comparable control strain was available, the frequency with which LLV and gs antigen were detected was similar to the other two selected strains. The greatest contrast was between selected Strain 1 and control Strain 5 in which the percentage of eggs with LLV in albumen was 1.4 and 21.4, respectively, and the percentage with gs antigen was 1.2 and 19.9. These differences between control and selected strains of chickens were not related to genetic cellular resistance to virus infection, because inoculation of chorioallantoic membranes with Rous sarcoma virus of subgroups A and B revealed that the proportion of birds resistant to subgroups A and B viruses was not greater in the selected strains than in the control strains.", "contents": "Effect of selection for high egg production in chickens on shedding of lymphoid leukosis virus and gs antigen into eggs. Lymphoid leukosis virus (LLV) and group specific (gs) viral antigen were detected less frequently in albumen of eggs from two strains of Single Comb White Leghorns that had been selected for high egg production than in corresponding random-bred control strains, which represented the original base population. In a third selected strain, for which no comparable control strain was available, the frequency with which LLV and gs antigen were detected was similar to the other two selected strains. The greatest contrast was between selected Strain 1 and control Strain 5 in which the percentage of eggs with LLV in albumen was 1.4 and 21.4, respectively, and the percentage with gs antigen was 1.2 and 19.9. These differences between control and selected strains of chickens were not related to genetic cellular resistance to virus infection, because inoculation of chorioallantoic membranes with Rous sarcoma virus of subgroups A and B revealed that the proportion of birds resistant to subgroups A and B viruses was not greater in the selected strains than in the control strains."}
{"id": "PMID:231258", "title": "Effect of gamma irradiation, fractionation, and penicillin supplementation on the rachitogenic activity of rye for chicks.", "content": "Experiments were conducted to study the effect of gamma irradiation on the rye-vitamin D antagonism in broiler chicks. In an initial study, the irradiated grain was exposed to gamma rays for 6 hr (2 Mrad) and was fed to rachitic chicks for only 12 hr before a single oral dose of vitamin D3. In another trial, birds were fed during the entire experiment (12 days) on the different experimental diets, and the irradiated grain was exposed to gamma rays for 20 hr. Results indicate that the factor in rye that interferes with vitamin D utilization was largely inactivated by exposing this grain to gamma rays for 20 hr. Additional information is reported in this paper related to the alleviation by extraction or antibiotic supplementation on the rachitogenic properties of rye. These studies were conducted by feeding to rachitic chicks the test materials for only a short period of time (12 hr) before a vitamin D3 oral dose and measuring the bone mineralization 48 hr later. Results indicate that the rachitogenic factor in rye is not present in the ash portion of the grain, that it can be largely overcome by water extraction and penicillin supplementation, and that an organic solvent extraction has no effect. Cooked beans which depress growth and increase the growth response to antibiotics are not rachitogenic.", "contents": "Effect of gamma irradiation, fractionation, and penicillin supplementation on the rachitogenic activity of rye for chicks. Experiments were conducted to study the effect of gamma irradiation on the rye-vitamin D antagonism in broiler chicks. In an initial study, the irradiated grain was exposed to gamma rays for 6 hr (2 Mrad) and was fed to rachitic chicks for only 12 hr before a single oral dose of vitamin D3. In another trial, birds were fed during the entire experiment (12 days) on the different experimental diets, and the irradiated grain was exposed to gamma rays for 20 hr. Results indicate that the factor in rye that interferes with vitamin D utilization was largely inactivated by exposing this grain to gamma rays for 20 hr. Additional information is reported in this paper related to the alleviation by extraction or antibiotic supplementation on the rachitogenic properties of rye. These studies were conducted by feeding to rachitic chicks the test materials for only a short period of time (12 hr) before a vitamin D3 oral dose and measuring the bone mineralization 48 hr later. Results indicate that the rachitogenic factor in rye is not present in the ash portion of the grain, that it can be largely overcome by water extraction and penicillin supplementation, and that an organic solvent extraction has no effect. Cooked beans which depress growth and increase the growth response to antibiotics are not rachitogenic."}
{"id": "PMID:231260", "title": "The relationship between Ca2+-mediated polyphosphoinositide phosphodiesterase activity, 1, 2-diacylglycerol accumulation, and microvesiculation in erythrocytes.", "content": "A variety of morphologic and metabolic changes occur in erythrocytes in which the intracellular level of Ca2+ is increased. These include echinocytosis followed by microvesiculation, K+ efflux, ATP degradation, and activation of polyphosphoinositide phosphodiesterase with the formation of 1,2-diacylglycerol and phosphatidate. The relationships between these changes are discussed and an attempt is made to assess their significance in both normal and aged cells.", "contents": "The relationship between Ca2+-mediated polyphosphoinositide phosphodiesterase activity, 1, 2-diacylglycerol accumulation, and microvesiculation in erythrocytes. A variety of morphologic and metabolic changes occur in erythrocytes in which the intracellular level of Ca2+ is increased. These include echinocytosis followed by microvesiculation, K+ efflux, ATP degradation, and activation of polyphosphoinositide phosphodiesterase with the formation of 1,2-diacylglycerol and phosphatidate. The relationships between these changes are discussed and an attempt is made to assess their significance in both normal and aged cells."}
{"id": "PMID:231262", "title": "Maternal responsiveness in the squirrel monkey following chronic administration of delta 9-THC.", "content": "Mother squirrel monkeys were orally administered gradually increasing doses of delta 9-THC (from 0.5 to 5.0 mg/kg) 5 days/wk from 2 wk to approximately 6 mo after birth. After having received a dose of 5.0 mg/kg for an average of 3.5 mo, drug-treated mothers were then compared with control mothers in terms of theri responsiveness both to their own and to unrelated infants. In contrast to the control mothers whose response pattern clearly showed differentiation of their own and other infants, the mothers that received delta 9-THC responded in much the same manner to the alien infant as they did to their own infant. The results show that the behavior of the THC-exposed mothers was not attributed simply to a general reduction in their responsiveness toward their offspring or to an overall reduction in their own state of arousal. Rather, the results suggest that chronic ingestion of delta 9-THC caused the mothers to be less disturbed by separation from their infants and/or produced degree of perceptual distortion that prevented them from responding selectively to the different infants.", "contents": "Maternal responsiveness in the squirrel monkey following chronic administration of delta 9-THC. Mother squirrel monkeys were orally administered gradually increasing doses of delta 9-THC (from 0.5 to 5.0 mg/kg) 5 days/wk from 2 wk to approximately 6 mo after birth. After having received a dose of 5.0 mg/kg for an average of 3.5 mo, drug-treated mothers were then compared with control mothers in terms of theri responsiveness both to their own and to unrelated infants. In contrast to the control mothers whose response pattern clearly showed differentiation of their own and other infants, the mothers that received delta 9-THC responded in much the same manner to the alien infant as they did to their own infant. The results show that the behavior of the THC-exposed mothers was not attributed simply to a general reduction in their responsiveness toward their offspring or to an overall reduction in their own state of arousal. Rather, the results suggest that chronic ingestion of delta 9-THC caused the mothers to be less disturbed by separation from their infants and/or produced degree of perceptual distortion that prevented them from responding selectively to the different infants."}
{"id": "PMID:231264", "title": "Baclofen and cerebellar cyclic GMP levels in mice.", "content": "Baclofen (3.5--10.0 mg/kg) dose dependently decreased cerebellar cyclic GMP content in mice correlated to a reduction in locomotor activity. Pretreatment with baclofen antagonized the rise in cerebellar cyclic GMP content induced by isoniazid and picrotoxin, but did not affect the increase in cyclic GMP following administration of pentetrazole. Baclofen had little effect on the arecoline-induced changes in cerebellar cyclic GMP content. Therefore, our data support the concept of gamma-aminobutyric acid agonistic properties of baclofen at presynaptic sites.", "contents": "Baclofen and cerebellar cyclic GMP levels in mice. Baclofen (3.5--10.0 mg/kg) dose dependently decreased cerebellar cyclic GMP content in mice correlated to a reduction in locomotor activity. Pretreatment with baclofen antagonized the rise in cerebellar cyclic GMP content induced by isoniazid and picrotoxin, but did not affect the increase in cyclic GMP following administration of pentetrazole. Baclofen had little effect on the arecoline-induced changes in cerebellar cyclic GMP content. Therefore, our data support the concept of gamma-aminobutyric acid agonistic properties of baclofen at presynaptic sites."}
{"id": "PMID:231265", "title": "1H-NMR effects in chloroquine-biopolymer binding interactions.", "content": "Chloroquine (CQ), an antimalarial and anti-inflammatory drug, is known to concentrate within lysosomes. 1H-NMR studies were conducted using the resonances of CQ itself during binding interactions with various polymers and proteins including lysosome fractions isolated from rodent livers by tritosome technique. Albumin, butyrylcholinesterase, and high molecular weight DNA interact with CQ, producing marked line-width changes that correlate with effective molecular weight. Triton WR-1339 and sucrose, probable contaminants of the lysosomal materials isolated, produced essentially no effect beyond a viscosity component. Lysosomal matrix and membrane fractions exhibited relatively weak interactions, membranes being the more tenacious toward CQ. Estimated binding constants are too small to permit explanation of CQ uptake in terms of protein affinity. The evidence is more consistent with a proton-pump trapping model proposed by de Duve et al.", "contents": "1H-NMR effects in chloroquine-biopolymer binding interactions. Chloroquine (CQ), an antimalarial and anti-inflammatory drug, is known to concentrate within lysosomes. 1H-NMR studies were conducted using the resonances of CQ itself during binding interactions with various polymers and proteins including lysosome fractions isolated from rodent livers by tritosome technique. Albumin, butyrylcholinesterase, and high molecular weight DNA interact with CQ, producing marked line-width changes that correlate with effective molecular weight. Triton WR-1339 and sucrose, probable contaminants of the lysosomal materials isolated, produced essentially no effect beyond a viscosity component. Lysosomal matrix and membrane fractions exhibited relatively weak interactions, membranes being the more tenacious toward CQ. Estimated binding constants are too small to permit explanation of CQ uptake in terms of protein affinity. The evidence is more consistent with a proton-pump trapping model proposed by de Duve et al."}
{"id": "PMID:231266", "title": "Semiconduction as the mechanism of the cytochrome oxidase reaction. Low activation energy of semiconduction measured for cytochrome oxidase protein. Solid state theory of cytochrome oxidase predicts observed kinetic peculiarities.", "content": "Cytochrome oxidase protein has a measured activation energy of semiconduction much smaller than that of other proteins, falling within the range of the activation energy of the cytochrome oxidase reaction in solution. Many kinetic peculiarities of the cytochrome oxidase reaction difficult to explain by mass-action theories are easily accounted for if semiconduction is assumed to be the controlling mechanism.", "contents": "Semiconduction as the mechanism of the cytochrome oxidase reaction. Low activation energy of semiconduction measured for cytochrome oxidase protein. Solid state theory of cytochrome oxidase predicts observed kinetic peculiarities. Cytochrome oxidase protein has a measured activation energy of semiconduction much smaller than that of other proteins, falling within the range of the activation energy of the cytochrome oxidase reaction in solution. Many kinetic peculiarities of the cytochrome oxidase reaction difficult to explain by mass-action theories are easily accounted for if semiconduction is assumed to be the controlling mechanism."}
{"id": "PMID:231275", "title": "[The effect of chloramphenicol on sleep in cat -- comparison with thiamphenicol, erythromycine, and oxytetracycline (author's transl)].", "content": "The effects of various antibiotics, which inhibit protein synthesis, has been studied on the sleep-waking cycle of cats. Chloramphenicol (CAP) selectively inhibits paradoxical sleep (SP). Thiamphenicol (TAP) and oxytetracycline however are ineffective; erythromycine induces only a small decrease of SP. When CAP is injected after TAP, the SP inhibition is longer than after CAP alone. Combining erythromycine and CAP produces the same effect as one or other of the antibiotic alone, depending only on the interval between administration of the two drugs. Slow wave sleep is decreased only with high doses of CAP and is unaffected by TAP, oxytetracycline or erythromycine. These results suggest that CAP may inhibit a peptide or protein synthesis involved in the mechanisms of SP.", "contents": "[The effect of chloramphenicol on sleep in cat -- comparison with thiamphenicol, erythromycine, and oxytetracycline (author's transl)]. The effects of various antibiotics, which inhibit protein synthesis, has been studied on the sleep-waking cycle of cats. Chloramphenicol (CAP) selectively inhibits paradoxical sleep (SP). Thiamphenicol (TAP) and oxytetracycline however are ineffective; erythromycine induces only a small decrease of SP. When CAP is injected after TAP, the SP inhibition is longer than after CAP alone. Combining erythromycine and CAP produces the same effect as one or other of the antibiotic alone, depending only on the interval between administration of the two drugs. Slow wave sleep is decreased only with high doses of CAP and is unaffected by TAP, oxytetracycline or erythromycine. These results suggest that CAP may inhibit a peptide or protein synthesis involved in the mechanisms of SP."}
{"id": "PMID:231276", "title": "DDC-induced amnesia and norepinephrine: a correlated behavioral-biochemical analysis.", "content": "Diethyldithiocarbamic acid (DDC), a dopamine-B-hydroxylase inhibitor, when injected into rats 30 min to 6 h before training of a passive avoidance task, impaired formation of long-term memory as indicated by performance on a retention test 24 h later. Performance of the task was at its minimum when injection occurred 2 to 4 h prior to training; recovery was evident in animals trained 5 or 6 h after drug treatment. Catecholamine assay of brains of temporally yoked animals showed that norepinephrine depletion followed a time course paralleling that of the amnesia. These findings support the hypothesis that the degree of memory storage, as reflected in performance following training in a passive avoidance task, can be directly correlated with the level of norepinephrine existing at the time of training.", "contents": "DDC-induced amnesia and norepinephrine: a correlated behavioral-biochemical analysis. Diethyldithiocarbamic acid (DDC), a dopamine-B-hydroxylase inhibitor, when injected into rats 30 min to 6 h before training of a passive avoidance task, impaired formation of long-term memory as indicated by performance on a retention test 24 h later. Performance of the task was at its minimum when injection occurred 2 to 4 h prior to training; recovery was evident in animals trained 5 or 6 h after drug treatment. Catecholamine assay of brains of temporally yoked animals showed that norepinephrine depletion followed a time course paralleling that of the amnesia. These findings support the hypothesis that the degree of memory storage, as reflected in performance following training in a passive avoidance task, can be directly correlated with the level of norepinephrine existing at the time of training."}
{"id": "PMID:231278", "title": "Strain differences in amphetamine sensitivity in mice. II. Overcompensation of paradoxical sleep after deprivation in two C57 strains.", "content": "d-Methylamphetamine (1--4 mg/kg) induced wakefulness for 3--5 h followed by paradoxical sleep (PS) rebound in C57BR, C57BL/6, and BALB/c mice. Slow-wave sleep (SWS) and PS suppression time were proportional to the given dose and different among strains. It was also dependent on the time of injection. Later PS rebound was significant in C57 strains, and in certain cases greater than PS loss, whereas rebound was small in BALB/c mice and PS loss was not completely compensated.", "contents": "Strain differences in amphetamine sensitivity in mice. II. Overcompensation of paradoxical sleep after deprivation in two C57 strains. d-Methylamphetamine (1--4 mg/kg) induced wakefulness for 3--5 h followed by paradoxical sleep (PS) rebound in C57BR, C57BL/6, and BALB/c mice. Slow-wave sleep (SWS) and PS suppression time were proportional to the given dose and different among strains. It was also dependent on the time of injection. Later PS rebound was significant in C57 strains, and in certain cases greater than PS loss, whereas rebound was small in BALB/c mice and PS loss was not completely compensated."}
{"id": "PMID:231279", "title": "Psychosocial risk factors in the developmental of infectious mononucleosis.", "content": "In a 4-year prospective seroepidemiological study of infectious mononucleosis (IM) of one class of some 1400 cadets at the West Point Military Academy, susceptibles and immunes were identified by the absence or presence of antibody to Epstein-Barr virus (EBV), the causative agent, and new infections by the appearance of antibody (seroconversion). On entry, about 1/3 lacked EBV antibody, of whom some 20% became infected (seroconverted); about 1/4 of seroconverters developed definite, clinical and recognized IM. Psychosocial factors that significantly increased the risk of clinical IM among seroconverters included: 1) having fathers who were \"overachievers\"; 2) having a high level of motivation; 3) doing relatively poorly academically. The combination of high motivation and poor academic performance interacted in predicting clinical IM. Additional data on presence of elevated titers among seroconverters with inapparent disease and on length of hospitalization among cases of clinical IM revealed that these two additional indices of infection or illness could also be predicted from the same set of psychosocial risk factors.", "contents": "Psychosocial risk factors in the developmental of infectious mononucleosis. In a 4-year prospective seroepidemiological study of infectious mononucleosis (IM) of one class of some 1400 cadets at the West Point Military Academy, susceptibles and immunes were identified by the absence or presence of antibody to Epstein-Barr virus (EBV), the causative agent, and new infections by the appearance of antibody (seroconversion). On entry, about 1/3 lacked EBV antibody, of whom some 20% became infected (seroconverted); about 1/4 of seroconverters developed definite, clinical and recognized IM. Psychosocial factors that significantly increased the risk of clinical IM among seroconverters included: 1) having fathers who were \"overachievers\"; 2) having a high level of motivation; 3) doing relatively poorly academically. The combination of high motivation and poor academic performance interacted in predicting clinical IM. Additional data on presence of elevated titers among seroconverters with inapparent disease and on length of hospitalization among cases of clinical IM revealed that these two additional indices of infection or illness could also be predicted from the same set of psychosocial risk factors."}
{"id": "PMID:231282", "title": "[Distribution, absorption and excretion of 198Au-colloid and Na251CrO4 in the chicken (author's transl)].", "content": "In order to clarify the suitability of 198Au-colloid and Na251CrO4 as a marker of transit of the gastrointestinal content of the chicken, the distribution, absorption and excretion of 198Au-colloid and Na251CrO4 in the chicken were examined. Orally administered 198Au-colloid was not absorbed by the gastrointestinal tract and excreted into feces. Intravenously injected 198Au-colloid was not excreted into the gastrointestinal tract through the gastrointestinal wall. On the other hand, orally administered Na251CrO4 was relatively well absorbed by the gastrointestinal tract and distributed over a whole body. Intravenously injected Na251CrO4 was excreted into the gastrointestinal tract through the gastrointestinal wall and bile ducts. It seemed that 198Au-colloid was not adhered to the gastrointestinal mucosa and consequently, the transport of 198Au-colloid in the gastrointestinal tract was not delayed. It is concluded that 198Au-colloid is highly suitable as a marker of gastrointestinal transit of the chicken but Na251CrO4 is unsuitable.", "contents": "[Distribution, absorption and excretion of 198Au-colloid and Na251CrO4 in the chicken (author's transl)]. In order to clarify the suitability of 198Au-colloid and Na251CrO4 as a marker of transit of the gastrointestinal content of the chicken, the distribution, absorption and excretion of 198Au-colloid and Na251CrO4 in the chicken were examined. Orally administered 198Au-colloid was not absorbed by the gastrointestinal tract and excreted into feces. Intravenously injected 198Au-colloid was not excreted into the gastrointestinal tract through the gastrointestinal wall. On the other hand, orally administered Na251CrO4 was relatively well absorbed by the gastrointestinal tract and distributed over a whole body. Intravenously injected Na251CrO4 was excreted into the gastrointestinal tract through the gastrointestinal wall and bile ducts. It seemed that 198Au-colloid was not adhered to the gastrointestinal mucosa and consequently, the transport of 198Au-colloid in the gastrointestinal tract was not delayed. It is concluded that 198Au-colloid is highly suitable as a marker of gastrointestinal transit of the chicken but Na251CrO4 is unsuitable."}
{"id": "PMID:231291", "title": "[Fibrous dysplasia of facial bones. 43 cases (author's transl)].", "content": "Clinical material of 43 patients treated for fibrous dysplasia of facial bones at the Department of Maxillofacial Surgery, Medical Academy in Cracov in the years 1956--1978 has been investigated. The author's own observations concerning diagnostics and treatment of these patients are presented. Diveristy of clinical forms and variability of the disease process dynamics likewise the difficulties in treatment resulting from unacquaintance with etiology of the disease are emphasized. The results of treatment obtained on the basis of control examination during two to fifteen-year periods of observation are described.", "contents": "[Fibrous dysplasia of facial bones. 43 cases (author's transl)]. Clinical material of 43 patients treated for fibrous dysplasia of facial bones at the Department of Maxillofacial Surgery, Medical Academy in Cracov in the years 1956--1978 has been investigated. The author's own observations concerning diagnostics and treatment of these patients are presented. Diveristy of clinical forms and variability of the disease process dynamics likewise the difficulties in treatment resulting from unacquaintance with etiology of the disease are emphasized. The results of treatment obtained on the basis of control examination during two to fifteen-year periods of observation are described."}
{"id": "PMID:231288", "title": "[Sleep organization by subjects in chronical post-traumatic inconscience (author's transl)].", "content": "Nine subjects who underwent a severe head traumatism with a brainstem dysfunction at the acute stage, were polygraphically recorded at the chronic stage under strict conditions of drug withdrawal and light-dark periods. Two groups of subjects were identified. The first one (5 subjects) showed normal NREM sleep and REM sleep morphologic patterns as well as a partly preserved architecture of sleep. The synchronisation of sleep with dark periods was lost in 4 out of 5 cases. In the second (4 subjects) NREM sleep morphologic patterns were lost and REM sleep was either uncertain or absent in 3 subjects. The synchronisation of sleep with dark periods was lost in 3 out of 4 cases. The morphologic alterations of sleep are connected with different types of encephalic lesions whereas the anomalies of the architecture of sleep and of its synchronisation with dark periods are referred to the numerous endogennous and exogenous stimuli undergone by these subjects. At the chronic stage of post-traumatic comas a 24-hour polygraphic recording supplies no definite information with regards to the prognosis.", "contents": "[Sleep organization by subjects in chronical post-traumatic inconscience (author's transl)]. Nine subjects who underwent a severe head traumatism with a brainstem dysfunction at the acute stage, were polygraphically recorded at the chronic stage under strict conditions of drug withdrawal and light-dark periods. Two groups of subjects were identified. The first one (5 subjects) showed normal NREM sleep and REM sleep morphologic patterns as well as a partly preserved architecture of sleep. The synchronisation of sleep with dark periods was lost in 4 out of 5 cases. In the second (4 subjects) NREM sleep morphologic patterns were lost and REM sleep was either uncertain or absent in 3 subjects. The synchronisation of sleep with dark periods was lost in 3 out of 4 cases. The morphologic alterations of sleep are connected with different types of encephalic lesions whereas the anomalies of the architecture of sleep and of its synchronisation with dark periods are referred to the numerous endogennous and exogenous stimuli undergone by these subjects. At the chronic stage of post-traumatic comas a 24-hour polygraphic recording supplies no definite information with regards to the prognosis."}
{"id": "PMID:231292", "title": "Plasma HDL cholesterol and the in vitro esterification of cholesterol.", "content": "In vitro esterification of plasma cholesterol was measured in twelve healthy subjects, six of whom had high plasma concentrations of high density lipoprotein (HDL) cholesterol, whereas the other six had low concentrations. Irrespective of the method used no difference between the groups with the respect to cholesterol esterification could be demonstrated. This may indicate that the beneficial effect of HDL on the development of atherosclerotic disease works thorugh other mechanisms than by facilitating the transport of cholesterol from peripheral tissues to the liver.", "contents": "Plasma HDL cholesterol and the in vitro esterification of cholesterol. In vitro esterification of plasma cholesterol was measured in twelve healthy subjects, six of whom had high plasma concentrations of high density lipoprotein (HDL) cholesterol, whereas the other six had low concentrations. Irrespective of the method used no difference between the groups with the respect to cholesterol esterification could be demonstrated. This may indicate that the beneficial effect of HDL on the development of atherosclerotic disease works thorugh other mechanisms than by facilitating the transport of cholesterol from peripheral tissues to the liver."}
{"id": "PMID:231293", "title": "High density lipoproteins, insulin secretion and coronary risk factors in latent coronary insufficiency.", "content": "Coronary heart disease (CHD) risk factors were studied in presumably healthy men, examined for preclinical CHD. Coronary angiography was performed in most \"latent CHD\" subjects. High density lipoprotein (HDL) cholesterol and apoproteins did not differ significantly between men with latent CHD (some with angiographic changes) and men without evidence of CHD. HDL cholesterol was positively correlated with physical activity. Insulin secretion was, however, positively associated with physical inactivity, body weight and serum triglycerides. Men with the highest insulin secretion had the lowest glucose tolerance. The study confirms the covariance between HDL cholesterol, insulin secretion, serum triglycerides, body weight and physical activity, but does not support the theory that HDL is a major \"negative risk factor\" in middle-aged men with preclinical CHD.", "contents": "High density lipoproteins, insulin secretion and coronary risk factors in latent coronary insufficiency. Coronary heart disease (CHD) risk factors were studied in presumably healthy men, examined for preclinical CHD. Coronary angiography was performed in most \"latent CHD\" subjects. High density lipoprotein (HDL) cholesterol and apoproteins did not differ significantly between men with latent CHD (some with angiographic changes) and men without evidence of CHD. HDL cholesterol was positively correlated with physical activity. Insulin secretion was, however, positively associated with physical inactivity, body weight and serum triglycerides. Men with the highest insulin secretion had the lowest glucose tolerance. The study confirms the covariance between HDL cholesterol, insulin secretion, serum triglycerides, body weight and physical activity, but does not support the theory that HDL is a major \"negative risk factor\" in middle-aged men with preclinical CHD."}
{"id": "PMID:231294", "title": "Role of cyclic AMP in glucagon-induced stimulation of hepatic glucose output in man.", "content": "The interrelationship between glucagon action on splanchnic glucose output and cyclic AMP production was studied in healthy volunteers after hepatic venous catheterization. Glucagon was infused according to four different protocols to achieve arterial levels ranging from 300 to 9000 ng/l. Infusion of glucagon which resulted in arterial levels of the hormone of 4000-9000 ng/l was associated with a marked increase in net splanchnic cyclic AMP production and in the arterial levels of the cyclic nucleotide. The rise in cyclic AMP efflux from the splanchnic area was transient but an augmented splanchnic production was still evident after 30 min of glucagon infusion. Splanchnic glucose output rose 3-5 fold. Infusion of glucagon at lower rates, resulting in arterial levels of 300-900 ng/l, did not measureably stimulate the efflux of cyclic AMP from the splanchnic area. In spite of this, splanchnic glucose output rose 2-3 fold and the blood glucose level increased 20-50% during glucagon infusion at these lower rates. It is concluded that (1) factors other than cyclic AMP are rate limiting in the stimulation of hepatic glucose production, and (2) although cyclic AMP is an established 'second messenger' of glucagon action, other factors may also be of importance in mediating the physiological response of this hormone.", "contents": "Role of cyclic AMP in glucagon-induced stimulation of hepatic glucose output in man. The interrelationship between glucagon action on splanchnic glucose output and cyclic AMP production was studied in healthy volunteers after hepatic venous catheterization. Glucagon was infused according to four different protocols to achieve arterial levels ranging from 300 to 9000 ng/l. Infusion of glucagon which resulted in arterial levels of the hormone of 4000-9000 ng/l was associated with a marked increase in net splanchnic cyclic AMP production and in the arterial levels of the cyclic nucleotide. The rise in cyclic AMP efflux from the splanchnic area was transient but an augmented splanchnic production was still evident after 30 min of glucagon infusion. Splanchnic glucose output rose 3-5 fold. Infusion of glucagon at lower rates, resulting in arterial levels of 300-900 ng/l, did not measureably stimulate the efflux of cyclic AMP from the splanchnic area. In spite of this, splanchnic glucose output rose 2-3 fold and the blood glucose level increased 20-50% during glucagon infusion at these lower rates. It is concluded that (1) factors other than cyclic AMP are rate limiting in the stimulation of hepatic glucose production, and (2) although cyclic AMP is an established 'second messenger' of glucagon action, other factors may also be of importance in mediating the physiological response of this hormone."}
{"id": "PMID:231295", "title": "A ten-year material of insulinoma: diagnosis and surgical treatment.", "content": "A 10-year series of patients operated for insulinoma at Sahlgren's Hospital, Gothenburg, is presented. Twelve patients (three men, nine women) aged 26--70 years are included in the material. The patients had a history of recurrent hypoglycemic symptoms of 1 month to 20 years. Hyperinsulinism was established by determinations of blood glucose and plasma insulin in the fasting state. Selective angiography could show the tumor in 3 out of the 12 patients. A through pancreatic mobilization and palpation was performed during operation. Solitary pancreatic tumor was found in 10 patients, and 1 of them had also metastases in the liver. One patient had two tumors, one in the head and one in the tail of the pancreas. In one patient it was not possible to find any tumor at operation. Distal pancreatic resection and splenectomy were performed when the tumor was localized in the body or tail or when no tumor was found. Tumours in the head were excised locally. Microscopy showed insulinoma without malignancy in 10 patients, malignant tumor in insulae with metastases in the liver in 1 patient, and multiple adenomatosis of insulae in the patient without any palpable tumor. The 11 patients with benign disease were examined 1--10 years after the operation and had no signs of hyperinsulinism or of diabetes.", "contents": "A ten-year material of insulinoma: diagnosis and surgical treatment. A 10-year series of patients operated for insulinoma at Sahlgren's Hospital, Gothenburg, is presented. Twelve patients (three men, nine women) aged 26--70 years are included in the material. The patients had a history of recurrent hypoglycemic symptoms of 1 month to 20 years. Hyperinsulinism was established by determinations of blood glucose and plasma insulin in the fasting state. Selective angiography could show the tumor in 3 out of the 12 patients. A through pancreatic mobilization and palpation was performed during operation. Solitary pancreatic tumor was found in 10 patients, and 1 of them had also metastases in the liver. One patient had two tumors, one in the head and one in the tail of the pancreas. In one patient it was not possible to find any tumor at operation. Distal pancreatic resection and splenectomy were performed when the tumor was localized in the body or tail or when no tumor was found. Tumours in the head were excised locally. Microscopy showed insulinoma without malignancy in 10 patients, malignant tumor in insulae with metastases in the liver in 1 patient, and multiple adenomatosis of insulae in the patient without any palpable tumor. The 11 patients with benign disease were examined 1--10 years after the operation and had no signs of hyperinsulinism or of diabetes."}
{"id": "PMID:231296", "title": "Clinical and morphological characteristics of colitis carcinoma and colorectal carcinoma in young people.", "content": "Two series of young patients (less than 40 years of age) with colorectal carcinoma (22 idiopathic carcinomas and 25 carcinomas complicating ulcerative proctocolitis), well matched for age and sex, were compared with regard to clinical features, tumour morphology and stage, and ultimate outcome after surgery. The cure rate in both series was low. Although a failure to diagnose colitis carcinoma accurately at an early stage might have contributed to the poor results, such a delay could hardly be responsible for the bad prognosis in patients with idiopathic carcinoma. The vast majority of the patients in both groups studied had highly malignant and/or mucoid adenocarcinoma, and surgery was palliative in about 40% of the patients in both series, owing to widespread dissemination. The general impression gained from this study of factors of histologic grade of malignancy, extent of spread, and survival rate was that colorectal carcinomas in the young, irrespective of being idiopathic or complicating ulcerative colitis, run a rapid course and have a gloomy prognosis. The outloook depends largely on the biologic characteristics of the tumours concerned. The results support previous statements that prophylactic surgery is justified in patients with long-standing ulcerative colitis with total involvement of the colon, particularly in the young. Regrettably, patients with idiopathic carcinoma will not have this chance.", "contents": "Clinical and morphological characteristics of colitis carcinoma and colorectal carcinoma in young people. Two series of young patients (less than 40 years of age) with colorectal carcinoma (22 idiopathic carcinomas and 25 carcinomas complicating ulcerative proctocolitis), well matched for age and sex, were compared with regard to clinical features, tumour morphology and stage, and ultimate outcome after surgery. The cure rate in both series was low. Although a failure to diagnose colitis carcinoma accurately at an early stage might have contributed to the poor results, such a delay could hardly be responsible for the bad prognosis in patients with idiopathic carcinoma. The vast majority of the patients in both groups studied had highly malignant and/or mucoid adenocarcinoma, and surgery was palliative in about 40% of the patients in both series, owing to widespread dissemination. The general impression gained from this study of factors of histologic grade of malignancy, extent of spread, and survival rate was that colorectal carcinomas in the young, irrespective of being idiopathic or complicating ulcerative colitis, run a rapid course and have a gloomy prognosis. The outloook depends largely on the biologic characteristics of the tumours concerned. The results support previous statements that prophylactic surgery is justified in patients with long-standing ulcerative colitis with total involvement of the colon, particularly in the young. Regrettably, patients with idiopathic carcinoma will not have this chance."}
{"id": "PMID:231297", "title": "Changes in the fecal flora of patients with Crohn's disease during treatment with metronidazole. A preliminary report.", "content": "Six patients with Crohn's disease and three healthy volunteers were treated with metronidazole. Before and during metronidazole treatment quantitative and qualitative studies of the aerobic and anaerobic fecal bacterial flora were performed, and the minimal inhibitory concentration (MIC) values for metronidazole of the isolated bacteria were determined. There was no significant change in the fecal flora of the volunteers during metronidazole treatment, but three patients who clinically responded well to treatment had drastically changed their anaerobic flora. Two patients did not respond to the metronidazole therapy. The total anaerobic count for one of them was unchanged, and the number of isolated anaerobic species was high during the treatment. The total anaerobic counts of the other non-responder decreased, but metronidazole-resistant (MIC greater than or equal to 40 microgram/ml) Gram-negative rods remained in the fecal samples. Furthermore, after 2 months his condition worsened, and he was given corticosteroids and parenteral nutrition. The result in one patient with a moderate response to therapy was intermediate. Our observations may explain why some patients benefit from metronidazole therapy and others do not.", "contents": "Changes in the fecal flora of patients with Crohn's disease during treatment with metronidazole. A preliminary report. Six patients with Crohn's disease and three healthy volunteers were treated with metronidazole. Before and during metronidazole treatment quantitative and qualitative studies of the aerobic and anaerobic fecal bacterial flora were performed, and the minimal inhibitory concentration (MIC) values for metronidazole of the isolated bacteria were determined. There was no significant change in the fecal flora of the volunteers during metronidazole treatment, but three patients who clinically responded well to treatment had drastically changed their anaerobic flora. Two patients did not respond to the metronidazole therapy. The total anaerobic count for one of them was unchanged, and the number of isolated anaerobic species was high during the treatment. The total anaerobic counts of the other non-responder decreased, but metronidazole-resistant (MIC greater than or equal to 40 microgram/ml) Gram-negative rods remained in the fecal samples. Furthermore, after 2 months his condition worsened, and he was given corticosteroids and parenteral nutrition. The result in one patient with a moderate response to therapy was intermediate. Our observations may explain why some patients benefit from metronidazole therapy and others do not."}
{"id": "PMID:231298", "title": "A study of infections and illnesses in a day nursery based on inclusion-bearing cells in the urine and infectious agent in faeces, urine and nasal secretion.", "content": "During an epidemic-free period of nearly 2 years infections and illnesses were followed in a group of small children (2-3 1/2 years) in a day nursery. The incidence of illness was fairly low, 6.3 per child and year. The viral infections were followed by means of the inclusion reaction in the urine and isolation of virus, and the bacterial by culture of nasal secretion. In 60% of the cases the viral infection was accompanied by illness. In 57 cases of illness there were 27 (47%) with merely virus and/or inclusion reaction, 8 (14%) in which bacteria alone were discovered, and 22 (39%) with both. The viral infections were the decisive ones in about 80% of the illnesses. Enteric respiratory viruses of 10 types were detected. 16 (73%) of the 22 children had such an infection on at least one occasion, and spread within the group occurred on infection with echovirus 9, coxsackievirus B4 and reovirus. Enteric viruses accounted for 29% of the viral infections. Streptococci and Mycoplasma pneumoniae played no part in the bacterial infections, which were entirely dominated by pneumococci. Cytomegaloviruria was found in 13 (72%) of 18 children examined. No spread was detected within the group. Rotavirus was on no occasion found in faeces.", "contents": "A study of infections and illnesses in a day nursery based on inclusion-bearing cells in the urine and infectious agent in faeces, urine and nasal secretion. During an epidemic-free period of nearly 2 years infections and illnesses were followed in a group of small children (2-3 1/2 years) in a day nursery. The incidence of illness was fairly low, 6.3 per child and year. The viral infections were followed by means of the inclusion reaction in the urine and isolation of virus, and the bacterial by culture of nasal secretion. In 60% of the cases the viral infection was accompanied by illness. In 57 cases of illness there were 27 (47%) with merely virus and/or inclusion reaction, 8 (14%) in which bacteria alone were discovered, and 22 (39%) with both. The viral infections were the decisive ones in about 80% of the illnesses. Enteric respiratory viruses of 10 types were detected. 16 (73%) of the 22 children had such an infection on at least one occasion, and spread within the group occurred on infection with echovirus 9, coxsackievirus B4 and reovirus. Enteric viruses accounted for 29% of the viral infections. Streptococci and Mycoplasma pneumoniae played no part in the bacterial infections, which were entirely dominated by pneumococci. Cytomegaloviruria was found in 13 (72%) of 18 children examined. No spread was detected within the group. Rotavirus was on no occasion found in faeces."}
{"id": "PMID:231299", "title": "Comparison of pivmecillinam and cephradine in bacteriuria in pregnancy and in acute urinary tract infection.", "content": "48 non-pregnant domiciliary patients referred by general practitioners and 50 pregnant women were treated for bacteriuria with either 500 mg cephradine or 400 mg pivmecillinam every 6 h for 7 days. In the pregnant women, cure rates were over 90% after 2 weeks for both compounds, and after 6 weeks were 86% for cephradine and 78% for pivmecillinam. Cure rates in the non-pregnant were 83% for cephradine and 95% for pivmecillinam at 6 weeks. Seven patients (3 given cephradine, 4 given pivmecillinam) stopped treatment due to side-effects. Overall, side-effects (many of which were trivial) were more common in patients treated with cephradine (51%) than in those receiving pivmecillinam (33%). It is concluded that both drugs are highly effective in these two common types of urinary infection.", "contents": "Comparison of pivmecillinam and cephradine in bacteriuria in pregnancy and in acute urinary tract infection. 48 non-pregnant domiciliary patients referred by general practitioners and 50 pregnant women were treated for bacteriuria with either 500 mg cephradine or 400 mg pivmecillinam every 6 h for 7 days. In the pregnant women, cure rates were over 90% after 2 weeks for both compounds, and after 6 weeks were 86% for cephradine and 78% for pivmecillinam. Cure rates in the non-pregnant were 83% for cephradine and 95% for pivmecillinam at 6 weeks. Seven patients (3 given cephradine, 4 given pivmecillinam) stopped treatment due to side-effects. Overall, side-effects (many of which were trivial) were more common in patients treated with cephradine (51%) than in those receiving pivmecillinam (33%). It is concluded that both drugs are highly effective in these two common types of urinary infection."}
{"id": "PMID:231300", "title": "Fulminant hepatitis A.", "content": "During a small epidemic of infectious hepatitis, a fulminant infection with fatal outcome occurred in a 54-year-old woman. IgM antibody to hepatitis A virus was demonstrated in the serum and large amounts of hepatitis A virus were found in the liver. It is suggested that the pathogenesis may be different for fulminant hepatitis A and B infection.", "contents": "Fulminant hepatitis A. During a small epidemic of infectious hepatitis, a fulminant infection with fatal outcome occurred in a 54-year-old woman. IgM antibody to hepatitis A virus was demonstrated in the serum and large amounts of hepatitis A virus were found in the liver. It is suggested that the pathogenesis may be different for fulminant hepatitis A and B infection."}
{"id": "PMID:231301", "title": "Infectious mononucleosis and agranulocytosis.", "content": "Infectious mononucleosis is often complicated by haematological abnormalities but agranulocytosis is so rare that a causal relationship has been questioned. We here describe 2 sisters, 3 and 5 years old, who both developed agranulocytosis or profound granulocytopenia 4-5 weeks after the acute onset of mononucleosis. No contributory cause could be found and we conclude that a constitutional disposition may be responsible for this complication.", "contents": "Infectious mononucleosis and agranulocytosis. Infectious mononucleosis is often complicated by haematological abnormalities but agranulocytosis is so rare that a causal relationship has been questioned. We here describe 2 sisters, 3 and 5 years old, who both developed agranulocytosis or profound granulocytopenia 4-5 weeks after the acute onset of mononucleosis. No contributory cause could be found and we conclude that a constitutional disposition may be responsible for this complication."}
{"id": "PMID:231302", "title": "Hepatitis A antibodies in Finland.", "content": "Serum specimens from 191 Finnish adults were tested for antibodies to hepatitis A virus (anti-HAV). The frequency of anti-HAV increased from 8% in the age group of 20-29 years to 92% in those older than 60 years. The level of 50% was reached between 40 and 50 years.", "contents": "Hepatitis A antibodies in Finland. Serum specimens from 191 Finnish adults were tested for antibodies to hepatitis A virus (anti-HAV). The frequency of anti-HAV increased from 8% in the age group of 20-29 years to 92% in those older than 60 years. The level of 50% was reached between 40 and 50 years."}
{"id": "PMID:231303", "title": "Kidney scintigraphy with 99mTc-DMSA and 131I-hippurate.", "content": "43 patients underwent an extended scintigraphic procedure with 99mTc-dimercaptosuccinylic acid in order to investigate its proper use for diagnosing morphological and functional kidney abnormalities. The group was comprised of patients without renal disease, and patients with diffuse parenchymal disease, obstructive uropathy, renal cysts and renal tumors. The study was followed by 131I-hippurate renography. We propose a simplified routine procedure with scintiphotos taken 10-15 min after injection for topographic information and 120 min after injection for renal morphology. This procedure allows excellent case finding of diffuse parenchymal disease of a special value in cases of radiological non-visualization. The technique is indicated, when iodine contrast media cannot be used for radiological examinations. DMSA studies, however, do not allow safe functional evaluation in all categories of patients. Neither can obstructive nephropathy be diagnosed unless the renal pelvis is dilated. Renal perfusion studies are contaminated by the perfusion of liver and spleen. Nevertheless, a tentative differentiation between cysts and tumours is possible, the former being hypoperfused the latter hyperperfused. When supplemented with gamma camera 131I-hippurate renography, the total scintigraphic procedure will also include split function determination and run-off evaluation.", "contents": "Kidney scintigraphy with 99mTc-DMSA and 131I-hippurate. 43 patients underwent an extended scintigraphic procedure with 99mTc-dimercaptosuccinylic acid in order to investigate its proper use for diagnosing morphological and functional kidney abnormalities. The group was comprised of patients without renal disease, and patients with diffuse parenchymal disease, obstructive uropathy, renal cysts and renal tumors. The study was followed by 131I-hippurate renography. We propose a simplified routine procedure with scintiphotos taken 10-15 min after injection for topographic information and 120 min after injection for renal morphology. This procedure allows excellent case finding of diffuse parenchymal disease of a special value in cases of radiological non-visualization. The technique is indicated, when iodine contrast media cannot be used for radiological examinations. DMSA studies, however, do not allow safe functional evaluation in all categories of patients. Neither can obstructive nephropathy be diagnosed unless the renal pelvis is dilated. Renal perfusion studies are contaminated by the perfusion of liver and spleen. Nevertheless, a tentative differentiation between cysts and tumours is possible, the former being hypoperfused the latter hyperperfused. When supplemented with gamma camera 131I-hippurate renography, the total scintigraphic procedure will also include split function determination and run-off evaluation."}
{"id": "PMID:231304", "title": "[Treatment of hyperlipidemia type II with soybeans].", "content": "15 outpatients with type II hyperlipoproteinemia (7 with type IIa and 8 with type IIb) were treated with soybean. This diet induced a significant decrease of plasma cholesterol levels from 314 +/- 24 to 267 +/- 30 mg/100 ml. Triglycerides levels remained unchanged. LDL-cholesterol decreased significantly from 241 +/- 26 to 194 +/- 32 mg/100 ml, whereas HDL-cholesterol increased only slightly and not significantly from 38 +/- 7 to 40 +/- 8 mg/100 ml. In our efforts to reduce hyperlipidemia the very low cost of these vegetable proteins is a further advantage. The hypocholesterolemic mechanism of soybean diet is unknown.", "contents": "[Treatment of hyperlipidemia type II with soybeans]. 15 outpatients with type II hyperlipoproteinemia (7 with type IIa and 8 with type IIb) were treated with soybean. This diet induced a significant decrease of plasma cholesterol levels from 314 +/- 24 to 267 +/- 30 mg/100 ml. Triglycerides levels remained unchanged. LDL-cholesterol decreased significantly from 241 +/- 26 to 194 +/- 32 mg/100 ml, whereas HDL-cholesterol increased only slightly and not significantly from 38 +/- 7 to 40 +/- 8 mg/100 ml. In our efforts to reduce hyperlipidemia the very low cost of these vegetable proteins is a further advantage. The hypocholesterolemic mechanism of soybean diet is unknown."}
{"id": "PMID:231306", "title": "[Diabetes and chronic pancreatitis. Report of twenty cases (author's transl)].", "content": "The association of chronic pancreatitis with diabetes is not very common. Men are the usual victims and ethylism the usual cause. The most common age of onset is between 40 and 50. Insulin treatment is much more frequent than for idiopathic diabetics. Diabetic heredity is probable. Calcifying pancreatitis is the most frequent form. Micro and macroangiopathic complications are found. A statistical comparative study with a matched series of idiopathic diabetics reveals no difference in the onset of vascular complications. The rate of triglycerides is statistically lower in pancreatitis (p less than 0.001). The other biological rates are the same (cholesterol, uricemy, alpha 2 macroglobulin). Diabetic stability is no more difficult to obtain than for idiopathic diabetics. In most cases the diet should be wide and alcohol must be prohibited.", "contents": "[Diabetes and chronic pancreatitis. Report of twenty cases (author's transl)]. The association of chronic pancreatitis with diabetes is not very common. Men are the usual victims and ethylism the usual cause. The most common age of onset is between 40 and 50. Insulin treatment is much more frequent than for idiopathic diabetics. Diabetic heredity is probable. Calcifying pancreatitis is the most frequent form. Micro and macroangiopathic complications are found. A statistical comparative study with a matched series of idiopathic diabetics reveals no difference in the onset of vascular complications. The rate of triglycerides is statistically lower in pancreatitis (p less than 0.001). The other biological rates are the same (cholesterol, uricemy, alpha 2 macroglobulin). Diabetic stability is no more difficult to obtain than for idiopathic diabetics. In most cases the diet should be wide and alcohol must be prohibited."}
{"id": "PMID:231307", "title": "[Polyarthritis in leprosy (author's transl)].", "content": "Inflammatory rhumatisms simulating rheumatoid arthritis belong to the manifestations of the reactions of leprosy. Pathology of these arthritis variate with the type of reaction. In the present observations, it must probably be the transition from a tuberculoid leprosy to a lepromatosis form in which the immunological state looks like the lupus one.", "contents": "[Polyarthritis in leprosy (author's transl)]. Inflammatory rhumatisms simulating rheumatoid arthritis belong to the manifestations of the reactions of leprosy. Pathology of these arthritis variate with the type of reaction. In the present observations, it must probably be the transition from a tuberculoid leprosy to a lepromatosis form in which the immunological state looks like the lupus one."}
{"id": "PMID:231308", "title": "[Comparative results of 99mTc scintigraphy and computerized tomography after contrast injection in cerebral pathology (author's transl)].", "content": "140 patients have been investigated by means of computerized tomography (CT) after contrast injection and radionuclide scan (RN scan). For patients with stroke (56 cases), RN uptake was more frequent (80%) at the 15th day of evolution, enhancement of hypodense images at CT reaches 100% at the 21st day. For the others pathologies (hematoma, tumors), the main difference between both examinations, was the volume of the lesions detected. RN uptake and CT enhancement both show the same blood brain barrier disturbance.", "contents": "[Comparative results of 99mTc scintigraphy and computerized tomography after contrast injection in cerebral pathology (author's transl)]. 140 patients have been investigated by means of computerized tomography (CT) after contrast injection and radionuclide scan (RN scan). For patients with stroke (56 cases), RN uptake was more frequent (80%) at the 15th day of evolution, enhancement of hypodense images at CT reaches 100% at the 21st day. For the others pathologies (hematoma, tumors), the main difference between both examinations, was the volume of the lesions detected. RN uptake and CT enhancement both show the same blood brain barrier disturbance."}
{"id": "PMID:231309", "title": "[Three cases of hereditary xanthinuria: review of the literature (author's transl)].", "content": "Xanthinuria is a rare hereditary disorder characterized by a gross deficiency of the enzyme xanthine oxydase resulting in hypouricemia, hypouricosuria and increased serum and urinary oxypurines. Three patients with this disease are presented and the pertinent literature is reviewed. We have demonstrated in one subject the absence of xanthine oxydase activity in a renal fragment. Genetic studies were performed but we do not find any relation between this deficiency of enzyme xanthine oxydase and HLA, Pl, Gm groups.", "contents": "[Three cases of hereditary xanthinuria: review of the literature (author's transl)]. Xanthinuria is a rare hereditary disorder characterized by a gross deficiency of the enzyme xanthine oxydase resulting in hypouricemia, hypouricosuria and increased serum and urinary oxypurines. Three patients with this disease are presented and the pertinent literature is reviewed. We have demonstrated in one subject the absence of xanthine oxydase activity in a renal fragment. Genetic studies were performed but we do not find any relation between this deficiency of enzyme xanthine oxydase and HLA, Pl, Gm groups."}
{"id": "PMID:231310", "title": "[Monocional immunoglobulins associated with bacterial endocarditis. Two case reports (author's transl)].", "content": "An IgGK monoclonal gammopathy occured in two patients with streptococcus viridans bacterial endocarditis. The gammopathy has been unchanged, respectively for 32 and 21 months following its detection. The alternate physiopathologic hypothesis are argued.", "contents": "[Monocional immunoglobulins associated with bacterial endocarditis. Two case reports (author's transl)]. An IgGK monoclonal gammopathy occured in two patients with streptococcus viridans bacterial endocarditis. The gammopathy has been unchanged, respectively for 32 and 21 months following its detection. The alternate physiopathologic hypothesis are argued."}
{"id": "PMID:231311", "title": "[Withdrawal effects following interruption of antihypertensive drugs. II. Coronary rebound phenomenon with antihypertensive drugs used in coronary heart disease therapy (author's transl)].", "content": "Treatment of hypertension is still primarily relevant of drug therapy. Prolonged use of antihypertensive agents is undoubtedly efficient but may induce when discontinued occasionally or intentionally a true rebound phenomenon i.e. exacerbation or aggravation of the pretreatment morbid condition. Hypertensive rebound occurs almost exclusively after clonidine withdrawal, usually abrupt but sometimes gradual. It consists of an acute clinical syndrome together with well defined biological findings, related to reactional enhanced sympathetic activity and necessitating an emergency treatment. A different rebound phenomenon is observed on withdrawal of some antihypertensive drugs when used in the management of coronary heart disease, namely beta adrenergic receptors blockers and specially propranolol. An acute exacerbation of coronary symptoms with or without severe arrythmias and eventually sudden deaths have been reported. The mechanisms responsible of this event are described, mainly the modifications recently observed at the level of the adrenoreceptors themselves. These two rebound phenomena although rare should be considered seriously by the practitioner while prescribing antihypertensive or antiangorous drugs otherwise very efficient but alble to induce catastrophic symptoms when interrupted in certain circumstancy.", "contents": "[Withdrawal effects following interruption of antihypertensive drugs. II. Coronary rebound phenomenon with antihypertensive drugs used in coronary heart disease therapy (author's transl)]. Treatment of hypertension is still primarily relevant of drug therapy. Prolonged use of antihypertensive agents is undoubtedly efficient but may induce when discontinued occasionally or intentionally a true rebound phenomenon i.e. exacerbation or aggravation of the pretreatment morbid condition. Hypertensive rebound occurs almost exclusively after clonidine withdrawal, usually abrupt but sometimes gradual. It consists of an acute clinical syndrome together with well defined biological findings, related to reactional enhanced sympathetic activity and necessitating an emergency treatment. A different rebound phenomenon is observed on withdrawal of some antihypertensive drugs when used in the management of coronary heart disease, namely beta adrenergic receptors blockers and specially propranolol. An acute exacerbation of coronary symptoms with or without severe arrythmias and eventually sudden deaths have been reported. The mechanisms responsible of this event are described, mainly the modifications recently observed at the level of the adrenoreceptors themselves. These two rebound phenomena although rare should be considered seriously by the practitioner while prescribing antihypertensive or antiangorous drugs otherwise very efficient but alble to induce catastrophic symptoms when interrupted in certain circumstancy."}
{"id": "PMID:231312", "title": "[Anatomo-clinical features of Castleman tumour. Report of a case with a membrano-proliferative glomerulonephritis (author's transl)].", "content": "A case of retro-peritoneal lymphoid angio-follicular hyperplasia or Castleman's pseudo-tumour with normochromic hormocytic anemia and membrano-proliferative glomerulonephritis is reported in a 53 year-old man. Since the first description by Castleman in 1954, 259 other cases have been published. The anatomo-clinical study of our observation and of 198 cases collected in the literature bears out 3 types of clinical forms, according to the location of the pseudo-tumour: mediastinal, superficial and abdominal. The first ones generally asymptomatic are the most frequent whereas the last ones, less common, are often associated with biological abnormalities. In spite of these differences such neoformations present the same morphologic features. They are round or ovoid and well delimited by a capsule. Under this capsule a lymphoid vascular tissue surrounds follicules with central capillaries or arterioles. When plasma cells infiltrate the stroma, perturbations such as anemia or hypoalbunemia appear. Besides a nephrotic syndrome has been discovered in our observation and in that of Humpherys. In all the cases the removal of the pseudo-tumour induces the retrogression of the biological abnormalities and of the nephrotic syndrome. Neither a recidive nor another location of the disease are noticed later on. This evolution is probably the fact of a benign hyperplatic process which grows after an antigenic stimulation.", "contents": "[Anatomo-clinical features of Castleman tumour. Report of a case with a membrano-proliferative glomerulonephritis (author's transl)]. A case of retro-peritoneal lymphoid angio-follicular hyperplasia or Castleman's pseudo-tumour with normochromic hormocytic anemia and membrano-proliferative glomerulonephritis is reported in a 53 year-old man. Since the first description by Castleman in 1954, 259 other cases have been published. The anatomo-clinical study of our observation and of 198 cases collected in the literature bears out 3 types of clinical forms, according to the location of the pseudo-tumour: mediastinal, superficial and abdominal. The first ones generally asymptomatic are the most frequent whereas the last ones, less common, are often associated with biological abnormalities. In spite of these differences such neoformations present the same morphologic features. They are round or ovoid and well delimited by a capsule. Under this capsule a lymphoid vascular tissue surrounds follicules with central capillaries or arterioles. When plasma cells infiltrate the stroma, perturbations such as anemia or hypoalbunemia appear. Besides a nephrotic syndrome has been discovered in our observation and in that of Humpherys. In all the cases the removal of the pseudo-tumour induces the retrogression of the biological abnormalities and of the nephrotic syndrome. Neither a recidive nor another location of the disease are noticed later on. This evolution is probably the fact of a benign hyperplatic process which grows after an antigenic stimulation."}
{"id": "PMID:231313", "title": "[The giant ulcer of the stomach. Notes concerning 30 cases (author's transl)].", "content": "The giant stomach ulcer can be defined as a crater measuring more than 30 mm in diameter. This variety of stomach ulcer represents 10-15% of the whole range of gastric ulcers, but they are not quite different from the nosologic point of view. It appears effectively that no etiopathogenic clinical or evolving particular factors can distinguish this kind of ulcer from the niches of normal size. To be taken into consideration is the risk of transforming into cancer which is multiplied by 3 or 5 times when compared with normal stomach ulcers, whence the importance of the endoscopy with many biopsies. In spite of the endoscopy the percentage of error is 5%, this is the reason for which, when in doubt, the more or less extensive gastric resection of the total gastrectomy is required with even more necessity then in normal cases of ulcers.", "contents": "[The giant ulcer of the stomach. Notes concerning 30 cases (author's transl)]. The giant stomach ulcer can be defined as a crater measuring more than 30 mm in diameter. This variety of stomach ulcer represents 10-15% of the whole range of gastric ulcers, but they are not quite different from the nosologic point of view. It appears effectively that no etiopathogenic clinical or evolving particular factors can distinguish this kind of ulcer from the niches of normal size. To be taken into consideration is the risk of transforming into cancer which is multiplied by 3 or 5 times when compared with normal stomach ulcers, whence the importance of the endoscopy with many biopsies. In spite of the endoscopy the percentage of error is 5%, this is the reason for which, when in doubt, the more or less extensive gastric resection of the total gastrectomy is required with even more necessity then in normal cases of ulcers."}
{"id": "PMID:231314", "title": "[Urological problems in patients suffering from multiple sclerosis (author's transl)].", "content": "Despite the many urological problems which are to be found in patients suffering from multiple sclerosis, not much attention has been drawn upon this problem. We have done a complete urological evaluation of 25 patients suffering from this disease, and after reviewing the pathophysiology suggested a possible treatment.", "contents": "[Urological problems in patients suffering from multiple sclerosis (author's transl)]. Despite the many urological problems which are to be found in patients suffering from multiple sclerosis, not much attention has been drawn upon this problem. We have done a complete urological evaluation of 25 patients suffering from this disease, and after reviewing the pathophysiology suggested a possible treatment."}
{"id": "PMID:231315", "title": "[Polychimiotherapy and Waldenstr\u00f6m's macroglobulinemia (author's transl)].", "content": "A 63-year-old man, with a Waldenstr\u00f6m's disease discovered by cryoglobulinemia (ischemic lesions of fingers) was quickly aggravating (hyperviscosity syndrome) under treatment by chlorambucil in a dosage of 8 mg daily. We obtained a dramatic remission with combination of cyclophosphamide, vincristine, adriamycin and prednisone surrounding a total body irradiation. A new trial of polychimiotherapy (with lower dosage) for severe Waldenstr\u00f6m's disease is actually on study.", "contents": "[Polychimiotherapy and Waldenstr\u00f6m's macroglobulinemia (author's transl)]. A 63-year-old man, with a Waldenstr\u00f6m's disease discovered by cryoglobulinemia (ischemic lesions of fingers) was quickly aggravating (hyperviscosity syndrome) under treatment by chlorambucil in a dosage of 8 mg daily. We obtained a dramatic remission with combination of cyclophosphamide, vincristine, adriamycin and prednisone surrounding a total body irradiation. A new trial of polychimiotherapy (with lower dosage) for severe Waldenstr\u00f6m's disease is actually on study."}
{"id": "PMID:231316", "title": "[Treatment of behavioral and affective disorder in alcoholic and geriatric patients (author's transl)].", "content": "Tiapride, a new drug of the anisamides' family, offers not only a major effectiveness on physical disease in alcoholism, but also on behavioral or affective disorder such agitation, hostility, impulsivity in alcoholic or in geriatric patients; this particular effectiveness is presented through the study of a sample of 15 alcoholic and geriatric patients.", "contents": "[Treatment of behavioral and affective disorder in alcoholic and geriatric patients (author's transl)]. Tiapride, a new drug of the anisamides' family, offers not only a major effectiveness on physical disease in alcoholism, but also on behavioral or affective disorder such agitation, hostility, impulsivity in alcoholic or in geriatric patients; this particular effectiveness is presented through the study of a sample of 15 alcoholic and geriatric patients."}
{"id": "PMID:231317", "title": "[Peripheral thrombophlebitis. \"Paratuberculous syndrome\" (author's transl)].", "content": "The authors relate the case of a young North-African man who presented during one month several peripheral thrombophlebitis before a ganglionary tuberculosis of the mediastinum appear. With specific antibiotherapy, the cutaneous lesions disappear and can be so considered as a paratuberculous syndroma.", "contents": "[Peripheral thrombophlebitis. \"Paratuberculous syndrome\" (author's transl)]. The authors relate the case of a young North-African man who presented during one month several peripheral thrombophlebitis before a ganglionary tuberculosis of the mediastinum appear. With specific antibiotherapy, the cutaneous lesions disappear and can be so considered as a paratuberculous syndroma."}
{"id": "PMID:231321", "title": "[Pulmonary fibrosis during a case of dermatomyositis (author's transl)].", "content": "The authors describe the case of a pulmonary interstitial fibrosis, the discovery of which preceeded the skin and muscular manifestations of dermatomyositis which was confirmed by a muscular biopsy. The aetiopathogenesis of the pulmonary disorder is not well known, nevertheless an immunological mechanism demonstrated in the experimental myositis is suggested but has yet to be proved.", "contents": "[Pulmonary fibrosis during a case of dermatomyositis (author's transl)]. The authors describe the case of a pulmonary interstitial fibrosis, the discovery of which preceeded the skin and muscular manifestations of dermatomyositis which was confirmed by a muscular biopsy. The aetiopathogenesis of the pulmonary disorder is not well known, nevertheless an immunological mechanism demonstrated in the experimental myositis is suggested but has yet to be proved."}
{"id": "PMID:231320", "title": "[A further case of IgD myeloma (author's transl)].", "content": "A 76-year-old woman was hospitalized for stabilization of her diabetic condition. The results of radiological, hematological, and biochemical investigations suggested the diagnosis of an IgD myeloma. A specific immune-serum was used to demonstrate the presence of monoclonal protein of the IgD lambda type. The course of the disease was very rapid and death occurred within 19 days from acute renal failure. The authors emphasize the various factors demonstrating the original nature of this observation and conclude by insisting on the necessity to use anti-heavy chains delta and epsilon during the diagnostic investigations for minoclonal gammapathies.", "contents": "[A further case of IgD myeloma (author's transl)]. A 76-year-old woman was hospitalized for stabilization of her diabetic condition. The results of radiological, hematological, and biochemical investigations suggested the diagnosis of an IgD myeloma. A specific immune-serum was used to demonstrate the presence of monoclonal protein of the IgD lambda type. The course of the disease was very rapid and death occurred within 19 days from acute renal failure. The authors emphasize the various factors demonstrating the original nature of this observation and conclude by insisting on the necessity to use anti-heavy chains delta and epsilon during the diagnostic investigations for minoclonal gammapathies."}
{"id": "PMID:231322", "title": "[Biochemical and experimental aspects of the lipid-lowering drugs pharmacology (author's transl)].", "content": "The analysis of the mode of action of lipid-lowering drugs requires a better understanding of the lipoprotein and cholesterol metabolism processes. The strides observed during the last years in this field are conditioning the development of pharmacologic and therapeutic researches. Moreover the use of new experimental models contributes to this progress by multiplying the study ways.", "contents": "[Biochemical and experimental aspects of the lipid-lowering drugs pharmacology (author's transl)]. The analysis of the mode of action of lipid-lowering drugs requires a better understanding of the lipoprotein and cholesterol metabolism processes. The strides observed during the last years in this field are conditioning the development of pharmacologic and therapeutic researches. Moreover the use of new experimental models contributes to this progress by multiplying the study ways."}
{"id": "PMID:231326", "title": "Cardiovascular nuclear medicine: an overview.", "content": "Some of the available cardiovascular nuclear medicine methods are incompletely validated, and others are incompletely developed. They are, however, of very great potential in diagnostic cardiology, and in patient management. A new era of clinical research and acute care monitoring has been opened by serial, noninvasive, hemodynamic measurements of right ventricular as well as left ventricular function. Stress testing has become more specific, and should, with future developments, become more specific, and should, with future developments, become more sensitive, using radionuclide procedures. Serious quality control and validation questions concerning thallium stress testing must be addressed. Intracoronary injection of radiogases has great potential, although minimal present application. Emission computerized tomography will be an important research tool. Compartmental analysis modeling of first pass tracer injections has much to offer, but is not yet validated. Present growth rate of these procedures is very rapid. Fully developed, cardiovascular nuclear medicine may become the largest component of clinical nuclear medicine practice.", "contents": "Cardiovascular nuclear medicine: an overview. Some of the available cardiovascular nuclear medicine methods are incompletely validated, and others are incompletely developed. They are, however, of very great potential in diagnostic cardiology, and in patient management. A new era of clinical research and acute care monitoring has been opened by serial, noninvasive, hemodynamic measurements of right ventricular as well as left ventricular function. Stress testing has become more specific, and should, with future developments, become more specific, and should, with future developments, become more sensitive, using radionuclide procedures. Serious quality control and validation questions concerning thallium stress testing must be addressed. Intracoronary injection of radiogases has great potential, although minimal present application. Emission computerized tomography will be an important research tool. Compartmental analysis modeling of first pass tracer injections has much to offer, but is not yet validated. Present growth rate of these procedures is very rapid. Fully developed, cardiovascular nuclear medicine may become the largest component of clinical nuclear medicine practice."}
{"id": "PMID:231318", "title": "[Post-partum galactorrhea with hyperprolactinaemia persistent during a clonidine treatment (author's transl)].", "content": "Persistence of a post-partum galactorrhea with an hyper-prolactinaemia leads to charge clonidin, an hypotensive-drug. When clonidine is stopped, galactorrhea and hyper-prolactinaemia case. Explanation of the role of the drug is uneasy.", "contents": "[Post-partum galactorrhea with hyperprolactinaemia persistent during a clonidine treatment (author's transl)]. Persistence of a post-partum galactorrhea with an hyper-prolactinaemia leads to charge clonidin, an hypotensive-drug. When clonidine is stopped, galactorrhea and hyper-prolactinaemia case. Explanation of the role of the drug is uneasy."}
{"id": "PMID:231323", "title": "[Laser applications in medicine and surgery (author's transl)].", "content": "After an analysis of the complex interweaving reactions of laser on biological materials, the laser applications in medicine and surgery are reviewed by the author. In ophthalmology its use is regular but not yet optimal. In otological applications the first results are good. In dermatology favorable results are obtained but the absence of special device had stopped his development. In surgery and endoscopy the best wave length must be chosen in reference to their hemostatic action and cutting, nevertheless in gastroscopy and bronchoscopy the laser seems to bring new therapeutic solutions. In odontology the pulsed lasers are dangerous for therapy but the holographic technique is a fertile research area. The author conclude to the necessary development of researches on the fundamental problems set by the biomedical applications of lasers.", "contents": "[Laser applications in medicine and surgery (author's transl)]. After an analysis of the complex interweaving reactions of laser on biological materials, the laser applications in medicine and surgery are reviewed by the author. In ophthalmology its use is regular but not yet optimal. In otological applications the first results are good. In dermatology favorable results are obtained but the absence of special device had stopped his development. In surgery and endoscopy the best wave length must be chosen in reference to their hemostatic action and cutting, nevertheless in gastroscopy and bronchoscopy the laser seems to bring new therapeutic solutions. In odontology the pulsed lasers are dangerous for therapy but the holographic technique is a fertile research area. The author conclude to the necessary development of researches on the fundamental problems set by the biomedical applications of lasers."}
{"id": "PMID:231319", "title": "[Primary intestinal lymphangiectasis or Waldmann's disease (author's transl)].", "content": "The authors report the observation of a primary intestinal lymphangiectasy diagnosed on a young girl sent for isolated edema of her inferior members, recently appeared. Clinical examination was normal. Biology found a low protein rate at 33 g/l and a low lymph rate : 183 L/mm3. Hepatic and renal records were normal. Test to marked albumin asserted the exsudative enteropathy with a fecal radio-activity of 3.6% (N 1%). Biopsy of the small intestines set out lymphangiectasies of the intestinal mucosa. Referring to this observation and to literature date, the authors realise a clinical and physiopathological analysis of Waldmann's disease or primary intestinal lymphangiectasy.", "contents": "[Primary intestinal lymphangiectasis or Waldmann's disease (author's transl)]. The authors report the observation of a primary intestinal lymphangiectasy diagnosed on a young girl sent for isolated edema of her inferior members, recently appeared. Clinical examination was normal. Biology found a low protein rate at 33 g/l and a low lymph rate : 183 L/mm3. Hepatic and renal records were normal. Test to marked albumin asserted the exsudative enteropathy with a fecal radio-activity of 3.6% (N 1%). Biopsy of the small intestines set out lymphangiectasies of the intestinal mucosa. Referring to this observation and to literature date, the authors realise a clinical and physiopathological analysis of Waldmann's disease or primary intestinal lymphangiectasy."}
{"id": "PMID:231324", "title": "[Effect and tolerance of Phanurane in the treatment of essential hypertension. (Double blind study) (author's transl)].", "content": "A double-blind study of Phanurane and placebo was conducted on 61 patients with mild essential hypertension. Each patient received 2 gelules daily (2 X 50 mg of canrenone) during a 2 month period. Statistical analysis has shown that patients on Phanurane experienced a significant decrease in systolic and diastolic blood pressure compared with patients on placebo. Clinical tolerance of canrenone was excellent. Uric acid and triglyceride levels remained normal.", "contents": "[Effect and tolerance of Phanurane in the treatment of essential hypertension. (Double blind study) (author's transl)]. A double-blind study of Phanurane and placebo was conducted on 61 patients with mild essential hypertension. Each patient received 2 gelules daily (2 X 50 mg of canrenone) during a 2 month period. Statistical analysis has shown that patients on Phanurane experienced a significant decrease in systolic and diastolic blood pressure compared with patients on placebo. Clinical tolerance of canrenone was excellent. Uric acid and triglyceride levels remained normal."}
{"id": "PMID:231325", "title": "[Therapeutic study of Daktacort in dermatological disorders (author's transl)].", "content": "The activity of Daktacort was studied in various types of mycotis skin ailments. A total of 40 cases were treated and results were very good in 34 cases and insufficient or nil in 6 cases. Tolerance was excellent.", "contents": "[Therapeutic study of Daktacort in dermatological disorders (author's transl)]. The activity of Daktacort was studied in various types of mycotis skin ailments. A total of 40 cases were treated and results were very good in 34 cases and insufficient or nil in 6 cases. Tolerance was excellent."}
{"id": "PMID:231334", "title": "[Decabromobiphenyl : toxicological study (author's transl)].", "content": "The paper presents results of experimental studies on a polybrominated flame retardant. Decabromobiphenyl was found not to be irritant to the rabbit skin or eye. The oral and dermal LD 50' in the rat are greater than 5 g/kg. In a 90 days feeding trial in rats no toxic effect were demonstrated at the levels of 100 and 500 ppm. However, hepatic change occured with diet containing 2.000 ppm. In a 4 weeks dust inhalation study, the no effect level was between 0.005 and 0.05 mg/l of air. The higher concentrations induced hepatic changes. Decabromobiphenyl was not teratogenic or embryotoxic to the rat at 10, 100 and 1.000 mg/kg per os. There was no evidence to indicate that the compound has mutagenic potential. Comparing the toxicological profile of decabromobiphenyl with other polybrominated biphenyl flame retardants would indicate that the toxicity decreases when the number of bromine atoms is increased.", "contents": "[Decabromobiphenyl : toxicological study (author's transl)]. The paper presents results of experimental studies on a polybrominated flame retardant. Decabromobiphenyl was found not to be irritant to the rabbit skin or eye. The oral and dermal LD 50' in the rat are greater than 5 g/kg. In a 90 days feeding trial in rats no toxic effect were demonstrated at the levels of 100 and 500 ppm. However, hepatic change occured with diet containing 2.000 ppm. In a 4 weeks dust inhalation study, the no effect level was between 0.005 and 0.05 mg/l of air. The higher concentrations induced hepatic changes. Decabromobiphenyl was not teratogenic or embryotoxic to the rat at 10, 100 and 1.000 mg/kg per os. There was no evidence to indicate that the compound has mutagenic potential. Comparing the toxicological profile of decabromobiphenyl with other polybrominated biphenyl flame retardants would indicate that the toxicity decreases when the number of bromine atoms is increased."}
{"id": "PMID:231335", "title": "Influence of chronic Cd intoxication on the alkaline phosphatase activity of liver and kidney; biochemical, histochemical and histological investigations.", "content": "To distinguish between: (a) the decrease of activity of alkaline phosphatase due to inhibition by cadmium; and (b) the decline of enzyme activity due to cell destruction, 20 adult female Wistar rats were treated 3 times/week with 0.5 mg/kg CdCl2 (by subcutaneous injection) during 28 weeks. Controls received the same volume of 0.9% NaCl solution. The animals were killed at different intervals. The liver and kidneys were investigated with biochemical, histochemical, light and electron microscopical techniques. The liver homogenates show an increase of alkaline phosphatase activity after about 12-13 weeks, whereas the activity of this enzyme in the kidney decreases. This activity could not be restored by the administration of Zn ions to the medium of the enzyme assay. However, in previous in vitro experiments the Cd inhibited alkaline phosphatase activity could be totally restored by such a Zn administration. By histochemical assay of alkaline phosphatase in the renal cortex a decrease of enzyme activity was demonstrated. By evaluation of the results obtained with light and electron microscopy, in combination with the biochemical results, the decrease of alkaline phosphatase activity in the kidney should  be considered as a real decrease in the amount of this enzyme due to cell degeneration.", "contents": "Influence of chronic Cd intoxication on the alkaline phosphatase activity of liver and kidney; biochemical, histochemical and histological investigations. To distinguish between: (a) the decrease of activity of alkaline phosphatase due to inhibition by cadmium; and (b) the decline of enzyme activity due to cell destruction, 20 adult female Wistar rats were treated 3 times/week with 0.5 mg/kg CdCl2 (by subcutaneous injection) during 28 weeks. Controls received the same volume of 0.9% NaCl solution. The animals were killed at different intervals. The liver and kidneys were investigated with biochemical, histochemical, light and electron microscopical techniques. The liver homogenates show an increase of alkaline phosphatase activity after about 12-13 weeks, whereas the activity of this enzyme in the kidney decreases. This activity could not be restored by the administration of Zn ions to the medium of the enzyme assay. However, in previous in vitro experiments the Cd inhibited alkaline phosphatase activity could be totally restored by such a Zn administration. By histochemical assay of alkaline phosphatase in the renal cortex a decrease of enzyme activity was demonstrated. By evaluation of the results obtained with light and electron microscopy, in combination with the biochemical results, the decrease of alkaline phosphatase activity in the kidney should  be considered as a real decrease in the amount of this enzyme due to cell degeneration."}
{"id": "PMID:231338", "title": "High pressure neurological syndrome: antagonistic effects of helium pressure and inhalation anesthetics on the dopamine-sensitive cyclic AMP response.", "content": "The antagonistic effects of helium pressure and certain inhalation anesthetics on the dopamine-sensitive cAMP response in the caudate nucleus of rat brain were examined. Helium pressure suppressed basal, dopamine-stimulated, and anesthetic-stimulated cAMP levels. These data indicate that by reversing the effects of pressure on dopaminergic transmission in the brain, inhalation ahesthetics may account for the improvement of some clinical symptoms of high pressure neurological syndrome (HPNS).", "contents": "High pressure neurological syndrome: antagonistic effects of helium pressure and inhalation anesthetics on the dopamine-sensitive cyclic AMP response. The antagonistic effects of helium pressure and certain inhalation anesthetics on the dopamine-sensitive cAMP response in the caudate nucleus of rat brain were examined. Helium pressure suppressed basal, dopamine-stimulated, and anesthetic-stimulated cAMP levels. These data indicate that by reversing the effects of pressure on dopaminergic transmission in the brain, inhalation ahesthetics may account for the improvement of some clinical symptoms of high pressure neurological syndrome (HPNS)."}
{"id": "PMID:231341", "title": "[Trial of a hyperimmune serum against para-influenza 3, bovine adenovirus 1, infectious rhinotracheitis and mucosal disease].", "content": "A four-valent serum was obtained by parallel hyperimmunization of cattle with live viral suspensions of parainfluenza-3, bovine adenovirus I, the virus of infectious rhinotracheitis and the mucous disease virus. The serum's neutralizing titres are between 1:1280 and 1:2560. The lasting exploitation of serum producing cattle indicates that no competition exists between the four antigens used in the process of hyperimmunization. Experimental testing of the serum on calves and its application in practical work proved its prophylactic and medicative effect. These results confirm the thesis that the use of passive immunoprophylaxis is needed in respiratory diseases of calves under conditions existing in intensive cattle-breeding.", "contents": "[Trial of a hyperimmune serum against para-influenza 3, bovine adenovirus 1, infectious rhinotracheitis and mucosal disease]. A four-valent serum was obtained by parallel hyperimmunization of cattle with live viral suspensions of parainfluenza-3, bovine adenovirus I, the virus of infectious rhinotracheitis and the mucous disease virus. The serum's neutralizing titres are between 1:1280 and 1:2560. The lasting exploitation of serum producing cattle indicates that no competition exists between the four antigens used in the process of hyperimmunization. Experimental testing of the serum on calves and its application in practical work proved its prophylactic and medicative effect. These results confirm the thesis that the use of passive immunoprophylaxis is needed in respiratory diseases of calves under conditions existing in intensive cattle-breeding."}
{"id": "PMID:231340", "title": "The experimental production of pneumonia in calves by intranasal inoculation of parainfluenza type III virus.", "content": "Thirteen colostrum deprived calves were inoculated with a low passage field strain of parainfluenza type III (PI 3) virus. Virus was administered by the intranasal route and the calves were experimentally infected twice daily for four consecutive days. Clinical signs of respiratory disease were noted and pneumonia was present in 12 animals at necropsy. PI 3 virus was isolated from the lung lesions and no other respiratory pathogens could be demonstrated. The pneumonic lesions grossly, histologically and in their distribution resembled those encountered in naturally occurring outbreaks of indoor calf pneumonia.", "contents": "The experimental production of pneumonia in calves by intranasal inoculation of parainfluenza type III virus. Thirteen colostrum deprived calves were inoculated with a low passage field strain of parainfluenza type III (PI 3) virus. Virus was administered by the intranasal route and the calves were experimentally infected twice daily for four consecutive days. Clinical signs of respiratory disease were noted and pneumonia was present in 12 animals at necropsy. PI 3 virus was isolated from the lung lesions and no other respiratory pathogens could be demonstrated. The pneumonic lesions grossly, histologically and in their distribution resembled those encountered in naturally occurring outbreaks of indoor calf pneumonia."}
{"id": "PMID:231344", "title": "A histoenzymological study of the saccus vasculosus of the freshwater teleost, Clarias batrachus (L.).", "content": "The saccus vasculosus (SV) of C. batrachus is comparatively small and situated latero-dorsal to the pituitary in between the lobi inferiores. It is in open communication with the third ventricle and is made up of coronet and supporting glial cells with interspersed liquor contacting neurons. These cellular constituents are arranged in one to three layers which are not thrown into folds. The PAS positive nature of the apical part of some coronet cells and their continuation with the PAS and AF positive material present in the lumen strongly suggest their secretory role. The coronet cells exhibited strong NADH diaphorase, NADPH diaphorase, cytochrome oxidase and MAO activity. AChE activity was comparatively weak. These enzyme histochemical studies show that SV has a dual function of transport and secretion. The strong MAO activity suggests the probable aminergic control of this organ.", "contents": "A histoenzymological study of the saccus vasculosus of the freshwater teleost, Clarias batrachus (L.). The saccus vasculosus (SV) of C. batrachus is comparatively small and situated latero-dorsal to the pituitary in between the lobi inferiores. It is in open communication with the third ventricle and is made up of coronet and supporting glial cells with interspersed liquor contacting neurons. These cellular constituents are arranged in one to three layers which are not thrown into folds. The PAS positive nature of the apical part of some coronet cells and their continuation with the PAS and AF positive material present in the lumen strongly suggest their secretory role. The coronet cells exhibited strong NADH diaphorase, NADPH diaphorase, cytochrome oxidase and MAO activity. AChE activity was comparatively weak. These enzyme histochemical studies show that SV has a dual function of transport and secretion. The strong MAO activity suggests the probable aminergic control of this organ."}
{"id": "PMID:231350", "title": "[Significance of hydrocyanic acid formation during fires].", "content": "Cyanide concentrations of blood samples from fire victims autopsied in the Institute of Legal Medicine, Munich, have been determined. In 25% of 48 analyzed cases cyanide concentrations from 0.52 microgram to 6.24 microgram Cyanide/ml blood have been detected. These results are compared to former studies and the higher mean level in our collective is emphasized. The importance of hydrocyanid acid in the toxicity of fire gases is evidently greater, than assumed. Hydrocyanic acid may be produced from nitrogen continaing polymers during combustion. The quote of these polymers in clothing, furniture, and also in equipment of cars is increasing. Therefore, it is necessary to take more notice of the formation of hydrocyanic acid during combustion, even though carbon monoxide is in general the main toxic agent in fire gases.", "contents": "[Significance of hydrocyanic acid formation during fires]. Cyanide concentrations of blood samples from fire victims autopsied in the Institute of Legal Medicine, Munich, have been determined. In 25% of 48 analyzed cases cyanide concentrations from 0.52 microgram to 6.24 microgram Cyanide/ml blood have been detected. These results are compared to former studies and the higher mean level in our collective is emphasized. The importance of hydrocyanid acid in the toxicity of fire gases is evidently greater, than assumed. Hydrocyanic acid may be produced from nitrogen continaing polymers during combustion. The quote of these polymers in clothing, furniture, and also in equipment of cars is increasing. Therefore, it is necessary to take more notice of the formation of hydrocyanic acid during combustion, even though carbon monoxide is in general the main toxic agent in fire gases."}
{"id": "PMID:231351", "title": "[Morphology of the adult human hyoid bone].", "content": "Investigations on 504 human hyoid bones show that there exist three main types, whose occurrence is, to a certain degree, sex-related. The junction between the body and the larger horns of the hyoid often is not ossified even in advanced age. Any determination of age on the basis of the extent of the corpus-cornu maius-ossification is most unreliable.", "contents": "[Morphology of the adult human hyoid bone]. Investigations on 504 human hyoid bones show that there exist three main types, whose occurrence is, to a certain degree, sex-related. The junction between the body and the larger horns of the hyoid often is not ossified even in advanced age. Any determination of age on the basis of the extent of the corpus-cornu maius-ossification is most unreliable."}
{"id": "PMID:231347", "title": "[Summarized extracellular postsynaptic potential of a single axon, an EEG quantum in the rabbit neocortex].", "content": "The possibility to record an EEG quantum following negative spikes with small amplitude was studied in the rabbit's neocortex. In about half of the averagings of the focal post-spike ECoGs recorded with a low-resistance microelectrode the spike was followed by a microsignal of synaptic form. The small amplitude and the negative sign of the spike's main phase pointed to a true extracellular leading off of biopotentials. A relatively small ratio between the amplitudes of the spikes and the post-spike signals shows that the latter are not afterpotentials of the spikes. They do not reflect discrete PSPs of single synapses, because they were recorded with relatively thick microelectrodes. The latency of the post-spike signals corresponded to their monosynaptic nature. Hence, the recorded signals are the EEG quanta. Their recording is a relatively simple procedure.", "contents": "[Summarized extracellular postsynaptic potential of a single axon, an EEG quantum in the rabbit neocortex]. The possibility to record an EEG quantum following negative spikes with small amplitude was studied in the rabbit's neocortex. In about half of the averagings of the focal post-spike ECoGs recorded with a low-resistance microelectrode the spike was followed by a microsignal of synaptic form. The small amplitude and the negative sign of the spike's main phase pointed to a true extracellular leading off of biopotentials. A relatively small ratio between the amplitudes of the spikes and the post-spike signals shows that the latter are not afterpotentials of the spikes. They do not reflect discrete PSPs of single synapses, because they were recorded with relatively thick microelectrodes. The latency of the post-spike signals corresponded to their monosynaptic nature. Hence, the recorded signals are the EEG quanta. Their recording is a relatively simple procedure."}
{"id": "PMID:231348", "title": "[Degree of homogeneity of the forms of statistical relationship between the EEG and spike currents of neurons].", "content": "The correlation between the spike activity and the waves of surface ECoG was studied in the visual and motor cortex of alert non-immobilized rabbits. A comparison was made between the forms of the obtained correlation functions for the cells with different horizontal and vertical distances between them. The analysis revealed the similarity of such functions in neurones of V-VI cortical layers, situated vertically under each other along the microelectrode track. Similar in form statistic connections between the ECoG and the background spike activity were also found, beginning with the depth of 1.000 mc, in the neurones situated at the same horizontal cortical level; however, with the increased distance between the cells the degree of similarity of these connections decreases in a non-linear way. On the basis of the obtained data a conclusion is made that the tangential sizes of the background functional ensembles of the cortical neurones are within the range of 140-300 mc.", "contents": "[Degree of homogeneity of the forms of statistical relationship between the EEG and spike currents of neurons]. The correlation between the spike activity and the waves of surface ECoG was studied in the visual and motor cortex of alert non-immobilized rabbits. A comparison was made between the forms of the obtained correlation functions for the cells with different horizontal and vertical distances between them. The analysis revealed the similarity of such functions in neurones of V-VI cortical layers, situated vertically under each other along the microelectrode track. Similar in form statistic connections between the ECoG and the background spike activity were also found, beginning with the depth of 1.000 mc, in the neurones situated at the same horizontal cortical level; however, with the increased distance between the cells the degree of similarity of these connections decreases in a non-linear way. On the basis of the obtained data a conclusion is made that the tangential sizes of the background functional ensembles of the cortical neurones are within the range of 140-300 mc."}
{"id": "PMID:231360", "title": "Synaptic function in the nervous system: a theory and its application.", "content": "The objective of this paper is to present a new theory of synaptic function in the nervous system. The basis for this theory is the experimental demonstration that a nerve impulse assumes five different forms as it advances through the synaptic region, and that five basic mathematical operations have been identified as being involved in the transformation of one form into another form. As a result of these data, the synaptic region is regarded as a functional unit where information coming to it is unpacked, processed, stored, and retrieved for transit to another synaptic region or effector site. The data also suggests that a nerve impulse is a bolus of energy, therefore, without substance; that it contains information coded in its shape or form; that it is precisely described mathematically. Furthermore, the data suggests synaptic regions process these nerve impulses by applying mathematical operations to them; that function in the synaptic region is highly stereotyped (programmed); that chemical substances are associated with the mathematical operations. The basic approach of this theory is to regard a significant portion of the nervous system as an 'interface' between the external universe and man himself. As an interface, the nervous system receives and processes information from both the external universe and man himself in a programmed manner. The interface functions by converting the information it receives into a bolus of energy, the nerve impulse, then processes the bolus by converting it into numbers or functions and applying mathematical operation to it.", "contents": "Synaptic function in the nervous system: a theory and its application. The objective of this paper is to present a new theory of synaptic function in the nervous system. The basis for this theory is the experimental demonstration that a nerve impulse assumes five different forms as it advances through the synaptic region, and that five basic mathematical operations have been identified as being involved in the transformation of one form into another form. As a result of these data, the synaptic region is regarded as a functional unit where information coming to it is unpacked, processed, stored, and retrieved for transit to another synaptic region or effector site. The data also suggests that a nerve impulse is a bolus of energy, therefore, without substance; that it contains information coded in its shape or form; that it is precisely described mathematically. Furthermore, the data suggests synaptic regions process these nerve impulses by applying mathematical operations to them; that function in the synaptic region is highly stereotyped (programmed); that chemical substances are associated with the mathematical operations. The basic approach of this theory is to regard a significant portion of the nervous system as an 'interface' between the external universe and man himself. As an interface, the nervous system receives and processes information from both the external universe and man himself in a programmed manner. The interface functions by converting the information it receives into a bolus of energy, the nerve impulse, then processes the bolus by converting it into numbers or functions and applying mathematical operation to it."}
{"id": "PMID:231361", "title": "[Suitability and recovery of capillary blood plasma for lipid determinations].", "content": "Plasma lipid analysis, particularly in population screening, can be facilitated by the use of capillary blood. A system for serial collection of capillary plasma is described. The concentrations of total cholesterol, HDL-cholesterol and triglycerides in heparinized capillary plasma and venous blood, respectively, are compared. No significant differences were found. Using the KAPA-method hemolytic samples are a source of error. They occurred with a frequency of about 3% in mass screening.", "contents": "[Suitability and recovery of capillary blood plasma for lipid determinations]. Plasma lipid analysis, particularly in population screening, can be facilitated by the use of capillary blood. A system for serial collection of capillary plasma is described. The concentrations of total cholesterol, HDL-cholesterol and triglycerides in heparinized capillary plasma and venous blood, respectively, are compared. No significant differences were found. Using the KAPA-method hemolytic samples are a source of error. They occurred with a frequency of about 3% in mass screening."}
{"id": "PMID:231362", "title": "[Action mechanism of vascular spasmolytics. 5. Drug-related relaxation and adenosine-3',5'-monophosphate content of isolated coronary arteries under conditions of fluoride-induced contracture].", "content": "Tetracaine and SKF 525-A as well as stimulators of adenylate cyclase and inhibitors of the nucleoside-3',5'-monophosphate phosphodiesterase have spasmolytic effects. At the fluoride-iuduced contracture -- a form of contracture independent of extracellular calcium -- tetracaine and SKF 525-A effect an additional increase in muscular tension. Their relaxing effect evidently presupposes a functioning calcium exchange. Drugs acting on the cAMP system have invariably spasmolytic effects at this contracture model, although they produced no change of the cAMP content under these conditions. An increase in total cAMP content is not obviously a necessary condition for the occurrence of drug-induced relaxation.", "contents": "[Action mechanism of vascular spasmolytics. 5. Drug-related relaxation and adenosine-3',5'-monophosphate content of isolated coronary arteries under conditions of fluoride-induced contracture]. Tetracaine and SKF 525-A as well as stimulators of adenylate cyclase and inhibitors of the nucleoside-3',5'-monophosphate phosphodiesterase have spasmolytic effects. At the fluoride-iuduced contracture -- a form of contracture independent of extracellular calcium -- tetracaine and SKF 525-A effect an additional increase in muscular tension. Their relaxing effect evidently presupposes a functioning calcium exchange. Drugs acting on the cAMP system have invariably spasmolytic effects at this contracture model, although they produced no change of the cAMP content under these conditions. An increase in total cAMP content is not obviously a necessary condition for the occurrence of drug-induced relaxation."}
{"id": "PMID:231364", "title": "Meningeal carcinomatosis from small cell carcinoma of the lung. Consequence of improved survival.", "content": "The cells of oat cell carcinoma of the lung can be identified in sputum because of their characteristic morphologic appearance. The cells from oat cell carcinomas can also be identified in other body fluids but are seen there less often. Spinal fluid involvement with oat cell carcinoma has been seen very infrequently, presumably because of a poor survival rate. Aggressive systemic chemotherapy has improved survival, and meningeal involvement is now being recognized as a complication. Of 62 patients treated by aggressive chemotherapy protocols, six (10%) were found to have leptomeningeal involvement by cytologic evaluation of cerebrospinal fluid (CSF). Involvement was found 6 to 13 months after the initiation of therapy. Two of the six patients had no evidence of CNS metastases by CAT brain scan. Necropsy was performed in three of the six cases and showed excellent histologic correlation with the cytologic findings. Because of most therapeutic drugs' poor penetration into the CSF, and because the spinal cord is not routinely irradiated, cytologic examination of the CSF from patients with oat cell carcinoma is necessary when there are new neurologic signs or symptoms to ensure proper, specific therapy.", "contents": "Meningeal carcinomatosis from small cell carcinoma of the lung. Consequence of improved survival. The cells of oat cell carcinoma of the lung can be identified in sputum because of their characteristic morphologic appearance. The cells from oat cell carcinomas can also be identified in other body fluids but are seen there less often. Spinal fluid involvement with oat cell carcinoma has been seen very infrequently, presumably because of a poor survival rate. Aggressive systemic chemotherapy has improved survival, and meningeal involvement is now being recognized as a complication. Of 62 patients treated by aggressive chemotherapy protocols, six (10%) were found to have leptomeningeal involvement by cytologic evaluation of cerebrospinal fluid (CSF). Involvement was found 6 to 13 months after the initiation of therapy. Two of the six patients had no evidence of CNS metastases by CAT brain scan. Necropsy was performed in three of the six cases and showed excellent histologic correlation with the cytologic findings. Because of most therapeutic drugs' poor penetration into the CSF, and because the spinal cord is not routinely irradiated, cytologic examination of the CSF from patients with oat cell carcinoma is necessary when there are new neurologic signs or symptoms to ensure proper, specific therapy."}
{"id": "PMID:231365", "title": "Cytologic, histologic and electron microscopic correlations in poorly differentiated primary lung carcinoma. A study of 43 cases.", "content": "For 43 poorly differentiated lung carcinomas we compared cytopathologic diagnoses made on specimens obtained prior to biopsy with histologic and electron microscopic diagnoses. Tissues were obtained by transbronchial biopsy, mediastinoscopy o pulmonary resection. Cytologies, tissues and electron micrographs were reviewed independently and blindly by five pathologists and one cytotechnologist. The cytologic, histologic and electron microscopic diagnoses agreed in 27 cases (62.7%), including adenocarcinoma (12), squamous carcinoma (five), oat cell carcinoma (six), mesothelioma (two) and adenosquamous carcinoma (two). In 14 cases the cytopathologic diagnoses had more accurately reflected the cell type ultimately diagnosed by electron microscopy than had the histologic diagnoses. Of ten poorly differentiated adenocarcinomas, eight had been interpreted as large-cell undifferentiated carcinomas, one as squamous carcinoma and one as poorly differentiated carcinoma histologically. Four poorly differentiated squamous carcinomas had been histologically diagnosed as giant cell, oat cell, undifferentiated carcinoma and adenocarcinoma. In these cases the previous cytologic diagnoses had been in agreement with the ultimate electron microscopic interpretation. The accuracy of cytodiagnoses may exceed that of histologic diagnoses in poorly differentiated lung cancer.", "contents": "Cytologic, histologic and electron microscopic correlations in poorly differentiated primary lung carcinoma. A study of 43 cases. For 43 poorly differentiated lung carcinomas we compared cytopathologic diagnoses made on specimens obtained prior to biopsy with histologic and electron microscopic diagnoses. Tissues were obtained by transbronchial biopsy, mediastinoscopy o pulmonary resection. Cytologies, tissues and electron micrographs were reviewed independently and blindly by five pathologists and one cytotechnologist. The cytologic, histologic and electron microscopic diagnoses agreed in 27 cases (62.7%), including adenocarcinoma (12), squamous carcinoma (five), oat cell carcinoma (six), mesothelioma (two) and adenosquamous carcinoma (two). In 14 cases the cytopathologic diagnoses had more accurately reflected the cell type ultimately diagnosed by electron microscopy than had the histologic diagnoses. Of ten poorly differentiated adenocarcinomas, eight had been interpreted as large-cell undifferentiated carcinomas, one as squamous carcinoma and one as poorly differentiated carcinoma histologically. Four poorly differentiated squamous carcinomas had been histologically diagnosed as giant cell, oat cell, undifferentiated carcinoma and adenocarcinoma. In these cases the previous cytologic diagnoses had been in agreement with the ultimate electron microscopic interpretation. The accuracy of cytodiagnoses may exceed that of histologic diagnoses in poorly differentiated lung cancer."}
{"id": "PMID:231369", "title": "Pharmacology of psoriasis.", "content": "Although psoriasis is a genetically transferred disease, little is known of the factors causing spontaneous eruption of a proliferative lesion in apparently normal epidermis. Cell kinetic studies indicate an increased epidermal turnover in clinically normal and involved skin, but the pharmacological events regulating epidermopoiesis remain elusive. Possible candidates for the defect in psoriasis are the cyclic nucleotides with their associated enzyme systems. The cyclic AMP: cyclic GMP ratio appears to be reduced in lesional skin. Further phosphodiesterase inhibitors are reported to improve psoriasis. Since prostaglandins stimulate epidermal cyclic AMP in vitro they have been investigated, but with conflicting results. However, the prostaglandins' precursor, arachidonic acid, appears to be elevated in the psoriatic lesion. Epidermal levels of cyclic AMP are also elevated by histamine via H2 receptors and the possibility that histamine exerts a regulatory role needs to be investigated. In conclusion, the pharmacology of psoriasis is complex. Not only do we need to know which pharmacological agents are present in abnormal amounts but more importantly we need to know more about their interactions with one another and with their specific epidermal 'receptors'.", "contents": "Pharmacology of psoriasis. Although psoriasis is a genetically transferred disease, little is known of the factors causing spontaneous eruption of a proliferative lesion in apparently normal epidermis. Cell kinetic studies indicate an increased epidermal turnover in clinically normal and involved skin, but the pharmacological events regulating epidermopoiesis remain elusive. Possible candidates for the defect in psoriasis are the cyclic nucleotides with their associated enzyme systems. The cyclic AMP: cyclic GMP ratio appears to be reduced in lesional skin. Further phosphodiesterase inhibitors are reported to improve psoriasis. Since prostaglandins stimulate epidermal cyclic AMP in vitro they have been investigated, but with conflicting results. However, the prostaglandins' precursor, arachidonic acid, appears to be elevated in the psoriatic lesion. Epidermal levels of cyclic AMP are also elevated by histamine via H2 receptors and the possibility that histamine exerts a regulatory role needs to be investigated. In conclusion, the pharmacology of psoriasis is complex. Not only do we need to know which pharmacological agents are present in abnormal amounts but more importantly we need to know more about their interactions with one another and with their specific epidermal 'receptors'."}
{"id": "PMID:231370", "title": "Thyrotrophin-responsive adenylate cyclase activity in thyroid toxic adenoma.", "content": "The adenylate cyclase system was studied in hyperfunctioning autonomous nodules in comparison with normal thyroid tissue. The basal, TSH- and NaF-stimulated adenylate cyclase activities were tested in purified plasma membrane preparations. Basal enzyme activity in membranes from hyperfunctioning nodules was variable and the response to TSH was either normal, low or absent. The present study demonstrates that an intact adenylate cyclase activity, hyporesponsive to TSH, may exist in the cell membrane of the adenoma.", "contents": "Thyrotrophin-responsive adenylate cyclase activity in thyroid toxic adenoma. The adenylate cyclase system was studied in hyperfunctioning autonomous nodules in comparison with normal thyroid tissue. The basal, TSH- and NaF-stimulated adenylate cyclase activities were tested in purified plasma membrane preparations. Basal enzyme activity in membranes from hyperfunctioning nodules was variable and the response to TSH was either normal, low or absent. The present study demonstrates that an intact adenylate cyclase activity, hyporesponsive to TSH, may exist in the cell membrane of the adenoma."}
{"id": "PMID:231367", "title": "Needle cytology of the breast. A quantitative and qualitative study of the cells of benign and malignant ductal neoplasia.", "content": "Twenty-seven ductal breast lesions, including cases of intraductal hyperplasia, intraductal carcinoma and infiltrating carcinoma, were studied cytologically by means of the Nordenstrom screw technique. Qualitative and quantitative cellular features were evaluated and correlated with histologic findings in sections taken from the region of needle tracts. This analysis indicated that a marked variation in nuclear size, the presence of macronucleoli, chromatin clumping, marked nuclear overlap and cellular disarray were indicators of malignancy. The last two features were the most specific and sensitive indicators of malignancy whereas the others were specific but only mildly sensitive. Some prediction of the degree of hyperplasia was possible with these morphologic criteria. Infiltrating carcinoma could not be distinguished cytologically from intraductal carcinoma.", "contents": "Needle cytology of the breast. A quantitative and qualitative study of the cells of benign and malignant ductal neoplasia. Twenty-seven ductal breast lesions, including cases of intraductal hyperplasia, intraductal carcinoma and infiltrating carcinoma, were studied cytologically by means of the Nordenstrom screw technique. Qualitative and quantitative cellular features were evaluated and correlated with histologic findings in sections taken from the region of needle tracts. This analysis indicated that a marked variation in nuclear size, the presence of macronucleoli, chromatin clumping, marked nuclear overlap and cellular disarray were indicators of malignancy. The last two features were the most specific and sensitive indicators of malignancy whereas the others were specific but only mildly sensitive. Some prediction of the degree of hyperplasia was possible with these morphologic criteria. Infiltrating carcinoma could not be distinguished cytologically from intraductal carcinoma."}
{"id": "PMID:231371", "title": "Responses of aldosterone-producing adenomas to ACTH and angiotensins.", "content": "To elucidate the control mechanism of aldosterone production in primary aldosteronism, in vivo and in vitro studies were done in 7 patients with aldosterone-producing adenomas. In the in vivo study, plasma aldosterone was stimulated more significantly by (Formula: see text), synthetic ACTH than by angiotensin II or furosemide. Diurnal variations of plasma aldosterone, which were studied in 4 patients, were similar to those seen in normal controls. In agreement with the results in the in vivo study, the in vitro study also revealed ACTH stimulated aldosterone and deoxycorticosterone (DOC) from the adenoma more markedly than angiotensin II or III. There was no adenoma which was more sensitivie to angiotenion II or III than to ACTH. From these results it is considered that changes in plasma aldosterone induced by the exogenous administration of angiotensin II or ACTH in patients with aldosterone-producing adenoma are mainly based on changes in aldosterone production in the adenoma. Furthermore, in patients with an aldosterone-producing adenoma in whom diurnal variations of plasma aldosterone similar to those in normal subjects are observed, responses of aldosterone to angiotensin II are supposed to be less than those to ACTH.", "contents": "Responses of aldosterone-producing adenomas to ACTH and angiotensins. To elucidate the control mechanism of aldosterone production in primary aldosteronism, in vivo and in vitro studies were done in 7 patients with aldosterone-producing adenomas. In the in vivo study, plasma aldosterone was stimulated more significantly by (Formula: see text), synthetic ACTH than by angiotensin II or furosemide. Diurnal variations of plasma aldosterone, which were studied in 4 patients, were similar to those seen in normal controls. In agreement with the results in the in vivo study, the in vitro study also revealed ACTH stimulated aldosterone and deoxycorticosterone (DOC) from the adenoma more markedly than angiotensin II or III. There was no adenoma which was more sensitivie to angiotenion II or III than to ACTH. From these results it is considered that changes in plasma aldosterone induced by the exogenous administration of angiotensin II or ACTH in patients with aldosterone-producing adenoma are mainly based on changes in aldosterone production in the adenoma. Furthermore, in patients with an aldosterone-producing adenoma in whom diurnal variations of plasma aldosterone similar to those in normal subjects are observed, responses of aldosterone to angiotensin II are supposed to be less than those to ACTH."}
{"id": "PMID:231372", "title": "Effects of enflurane anaesthesia and surgery on endocrine function in man.", "content": "Forty-five patients underwent enflurane anaesthesia and surgery. Anaesthesia alone evoked little change in the plasma concentrations of ACTH, cortisol or antidiuretic hormone (ADH), but there were significant increases during surgery. The plasma levels of aldosterone rose during anaesthesia alone, and a further increase was noted during surgery. Neither enflurane anaesthesia nor surgery significantly influenced plasma concentrations of renin activity and thyroxine. A significant decrease in the plasma triiodothyronine levels was detected during anaesthesia alone, and a further decrease was found during and following surgery. Enflurane anaesthesia did not affect the plasma level of luteinizing hormone (LH) in male subjects throughout surgery, but a significant decrease was detected in female patients on the first postoperative day. The plasma concentrations of testosterone decreased during anaesthesia alone and surgery, and a further decrease was noted on the first postoperative day.", "contents": "Effects of enflurane anaesthesia and surgery on endocrine function in man. Forty-five patients underwent enflurane anaesthesia and surgery. Anaesthesia alone evoked little change in the plasma concentrations of ACTH, cortisol or antidiuretic hormone (ADH), but there were significant increases during surgery. The plasma levels of aldosterone rose during anaesthesia alone, and a further increase was noted during surgery. Neither enflurane anaesthesia nor surgery significantly influenced plasma concentrations of renin activity and thyroxine. A significant decrease in the plasma triiodothyronine levels was detected during anaesthesia alone, and a further decrease was found during and following surgery. Enflurane anaesthesia did not affect the plasma level of luteinizing hormone (LH) in male subjects throughout surgery, but a significant decrease was detected in female patients on the first postoperative day. The plasma concentrations of testosterone decreased during anaesthesia alone and surgery, and a further decrease was noted on the first postoperative day."}
{"id": "PMID:231373", "title": "The effects of dexamethasone on the growth of gamma-irradiated tadpoles.", "content": "A plausible hypothesis as to the mode of action of dexamethasone (DXM) has been proposed. Growth of irradiated tadpoles of Bufo melanostictus, treated daily with the corticoid, is more suppressed. Compared with its antagonism with ACTH, its coordinate promotion of TSH production accelerates metamorphosis. This modulated feedback is consistent with the constant course of the hypothalamic nuclei influence upon the adenohypophyseal hormones.", "contents": "The effects of dexamethasone on the growth of gamma-irradiated tadpoles. A plausible hypothesis as to the mode of action of dexamethasone (DXM) has been proposed. Growth of irradiated tadpoles of Bufo melanostictus, treated daily with the corticoid, is more suppressed. Compared with its antagonism with ACTH, its coordinate promotion of TSH production accelerates metamorphosis. This modulated feedback is consistent with the constant course of the hypothalamic nuclei influence upon the adenohypophyseal hormones."}
{"id": "PMID:231366", "title": "Intranuclear cytoplasmic inclusions (invaginations) in thyroid aspirations. Frequency and specificity.", "content": "In order to determine the frequency and specificity of intranuclear cytoplasmic inclusions (invaginations), described by some as an important criterion for the cytologic diagnosis of thyroid carcinoma, 258 consecutive thyroid aspirates were reviewed. Intranuclear cytoplasmic inclusions were present in 91% of the papillary adenocarcinomas but were not seen in any of the benign thyroid lesions or in any of the few nonpapillary adenocarcinomas in the study. It is concluded that the presence of intranuclear cytoplasmic inclusions in thyroid aspirates is probably specific to thyroid carcinoma but is not necessarily restricted to the papillary variant.", "contents": "Intranuclear cytoplasmic inclusions (invaginations) in thyroid aspirations. Frequency and specificity. In order to determine the frequency and specificity of intranuclear cytoplasmic inclusions (invaginations), described by some as an important criterion for the cytologic diagnosis of thyroid carcinoma, 258 consecutive thyroid aspirates were reviewed. Intranuclear cytoplasmic inclusions were present in 91% of the papillary adenocarcinomas but were not seen in any of the benign thyroid lesions or in any of the few nonpapillary adenocarcinomas in the study. It is concluded that the presence of intranuclear cytoplasmic inclusions in thyroid aspirates is probably specific to thyroid carcinoma but is not necessarily restricted to the papillary variant."}
{"id": "PMID:231374", "title": "Intramuscular ACTH or placebo in the treatment of hyperemesis gravidarum.", "content": "Thirty-two women with hyperemesis gravidarum were treated with intramuscular ACTH (0.5 mg) or placebo for 4 days in a randomized double-blind trial. The two treatments were equally effective in relieving hyperemesis, although the function of the adrenal cortex was stimulated only during the ACTH therapy. The administration of ACTH thus appears useless for the treatment of severe vomiting in early pregnancy.", "contents": "Intramuscular ACTH or placebo in the treatment of hyperemesis gravidarum. Thirty-two women with hyperemesis gravidarum were treated with intramuscular ACTH (0.5 mg) or placebo for 4 days in a randomized double-blind trial. The two treatments were equally effective in relieving hyperemesis, although the function of the adrenal cortex was stimulated only during the ACTH therapy. The administration of ACTH thus appears useless for the treatment of severe vomiting in early pregnancy."}
{"id": "PMID:231376", "title": "Nephroblastoma. Results and complications of treatment.", "content": "Treatment results in 31 patients with nephroblastoma are reported. Survival seemed superior in patients who received Actinomycin-D in addition to surgery and postoperative irradiation. Twelve long-term surviving children were evaluated for side-effects of the treatment. Although inhibition of growth and other abnormalities occurred in most survivors, little permanent disability and dysfunction appears to have resulted from the treatment.", "contents": "Nephroblastoma. Results and complications of treatment. Treatment results in 31 patients with nephroblastoma are reported. Survival seemed superior in patients who received Actinomycin-D in addition to surgery and postoperative irradiation. Twelve long-term surviving children were evaluated for side-effects of the treatment. Although inhibition of growth and other abnormalities occurred in most survivors, little permanent disability and dysfunction appears to have resulted from the treatment."}
{"id": "PMID:231377", "title": "Labetalol-induced Peyronie's disease? A case report.", "content": "Peyronie's disease (induratio penis plastica) has been observed in a 58-year-old man 8 months after initiation of treatment with the new combined alpha- and beta-blocking agent, labetalol. During the last 2 months before onset of symptoms he had received 2400 mg labetalol daily. He showed no other signs of abnormal fibrous tissue production and the ANF test was negative. Cessation of the drug revealed no improvement. Peyronie's disease has also been observed in relation to treatment with propranolol, practolol and metoprolol and might be due to an impaired balance between alpha- and beta-receptors in connective tissue, but there may also be an immunological basis for the fibrosis. A possible coincidence is stressed, as the ages of the reported cases are within the range where this disease most often develops.", "contents": "Labetalol-induced Peyronie's disease? A case report. Peyronie's disease (induratio penis plastica) has been observed in a 58-year-old man 8 months after initiation of treatment with the new combined alpha- and beta-blocking agent, labetalol. During the last 2 months before onset of symptoms he had received 2400 mg labetalol daily. He showed no other signs of abnormal fibrous tissue production and the ANF test was negative. Cessation of the drug revealed no improvement. Peyronie's disease has also been observed in relation to treatment with propranolol, practolol and metoprolol and might be due to an impaired balance between alpha- and beta-receptors in connective tissue, but there may also be an immunological basis for the fibrosis. A possible coincidence is stressed, as the ages of the reported cases are within the range where this disease most often develops."}
{"id": "PMID:231379", "title": "Vapor detection using adsorptive solids probed by X-rays.", "content": "Activated carbon is used widely as a filter medium for trapping gases and vapors from the air. It is effective because of its large capacity even at low concentration levels. X-ray absorption measurements recently have been conducted on activated carbons before and after they have adsorbed certain organic gases. The measurements have shown that the X-ray absorption technique, when applied to porous adsorbing solids, is very sensitive for detecting low levels (less than 1 ppm) of many gases and vapors. The method is especially good for detecting compounds containing atoms having atomic numbers greater than 14. This is due to the increasing interaction of X-rays with matter as atomic number increases.", "contents": "Vapor detection using adsorptive solids probed by X-rays. Activated carbon is used widely as a filter medium for trapping gases and vapors from the air. It is effective because of its large capacity even at low concentration levels. X-ray absorption measurements recently have been conducted on activated carbons before and after they have adsorbed certain organic gases. The measurements have shown that the X-ray absorption technique, when applied to porous adsorbing solids, is very sensitive for detecting low levels (less than 1 ppm) of many gases and vapors. The method is especially good for detecting compounds containing atoms having atomic numbers greater than 14. This is due to the increasing interaction of X-rays with matter as atomic number increases."}
{"id": "PMID:231380", "title": "Problems in the aging of females using the Os pubis.", "content": "The Gilbert-McKern method for aging the female Os pubis has attained popularity following Gilbert's ('73) demonstration that the McKern-Stewart male standards are not directly applicable to females. In order to assess the reliability of the method, forensic anthropologists were asked to age a set of 11 pubes of known age. There was a great deal of variability in the responses of the 23 participants. Three, four, and five different responses (out of a 6-scale system) were given for each component of each pubic bone. Only 51% of the assessments yielded age ranges which would include the known age of the specimens. Analysis of the errors showed that one of the focal problems of the Gilbert-McKern system was the difficulty in judging whether the ventral rampart was building up or breaking down.", "contents": "Problems in the aging of females using the Os pubis. The Gilbert-McKern method for aging the female Os pubis has attained popularity following Gilbert's ('73) demonstration that the McKern-Stewart male standards are not directly applicable to females. In order to assess the reliability of the method, forensic anthropologists were asked to age a set of 11 pubes of known age. There was a great deal of variability in the responses of the 23 participants. Three, four, and five different responses (out of a 6-scale system) were given for each component of each pubic bone. Only 51% of the assessments yielded age ranges which would include the known age of the specimens. Analysis of the errors showed that one of the focal problems of the Gilbert-McKern system was the difficulty in judging whether the ventral rampart was building up or breaking down."}
{"id": "PMID:231381", "title": "Giant adrenal myelolipoma and testicular interstitial cell tumor in a man with congenital 21-hydroxylase deficiency.", "content": "The occurrence of a giant myelolipoma of the adrenal gland reported in a patient with congenital adrenal hyperplasia (21-hydroxylase deficiency). Associated significant findings include a massive proliferation of adrenocortical cells as an integral part of the myelolipoma and coincidental tumor of the interstitial cells of the testis. The clinical, radiologic, endocrinologic, and pathologic features of this case are correlated with a review of the literature. The additional myelolipomas are also reported here for the first time. Similar lesions have been induced experimentally in rats and provide further evidence suggesting a hyperplastic rather than a neoplastic nature for this complex lesion, at least in its earlier stages.", "contents": "Giant adrenal myelolipoma and testicular interstitial cell tumor in a man with congenital 21-hydroxylase deficiency. The occurrence of a giant myelolipoma of the adrenal gland reported in a patient with congenital adrenal hyperplasia (21-hydroxylase deficiency). Associated significant findings include a massive proliferation of adrenocortical cells as an integral part of the myelolipoma and coincidental tumor of the interstitial cells of the testis. The clinical, radiologic, endocrinologic, and pathologic features of this case are correlated with a review of the literature. The additional myelolipomas are also reported here for the first time. Similar lesions have been induced experimentally in rats and provide further evidence suggesting a hyperplastic rather than a neoplastic nature for this complex lesion, at least in its earlier stages."}
{"id": "PMID:231382", "title": "Malignant mixed m\u00fcllerian tumors of the uterus. A clinicopathologic assessment of 34 cases.", "content": "We have analyzed clinical and pathologic features of a series of 34 patients with malignant mixed m\u00fcllerian tumors of the uterus. This study includes 17 homologous and 17 heterologous lesions. The most significant prognostic indicator in our patients was tumor extent (stage) at diagnosis. Of lesser importance were the presence of heterologous elements, especially chondrosarcoma, high grade of carcinoma and tumor size. Survival rates were 52% at 2 years and 36% at 5 years for homologous tumors; and 47% and 14%, respectively, for the heterologous variety.", "contents": "Malignant mixed m\u00fcllerian tumors of the uterus. A clinicopathologic assessment of 34 cases. We have analyzed clinical and pathologic features of a series of 34 patients with malignant mixed m\u00fcllerian tumors of the uterus. This study includes 17 homologous and 17 heterologous lesions. The most significant prognostic indicator in our patients was tumor extent (stage) at diagnosis. Of lesser importance were the presence of heterologous elements, especially chondrosarcoma, high grade of carcinoma and tumor size. Survival rates were 52% at 2 years and 36% at 5 years for homologous tumors; and 47% and 14%, respectively, for the heterologous variety."}
{"id": "PMID:231383", "title": "Combined epithelial and sarcomatous elements in a liver cancer associated with oral contraceptive use.", "content": "A rare mixed malignant hepatic tumor in a 35-year-old woman is presented. Hepatic enlargement regressed and became stable for 3 years after contraceptive pills were discontinued. Exacerbation began 3 months prior to admission, at which time there was a spontaneous rupture of the tumor; this resulted in the death of the patient.", "contents": "Combined epithelial and sarcomatous elements in a liver cancer associated with oral contraceptive use. A rare mixed malignant hepatic tumor in a 35-year-old woman is presented. Hepatic enlargement regressed and became stable for 3 years after contraceptive pills were discontinued. Exacerbation began 3 months prior to admission, at which time there was a spontaneous rupture of the tumor; this resulted in the death of the patient."}
{"id": "PMID:231384", "title": "A unique ultrastructural variant of Wilms' tumor. Its possible histogenetic implications.", "content": "A report of a Wilms' tumor with hitherto undescribed ultrastructural and histochemical features is presented. The unique features conform structurally, and to some extent chemically to autophagosomes, which occur in similar abundance only in granular cell myoblastoma, recently considered to be derived from neural elements. The implication of this common structural feature readdresses attention to the work of Masson, who originally theorized a neurectodermal origin for the Wilms' tumor.", "contents": "A unique ultrastructural variant of Wilms' tumor. Its possible histogenetic implications. A report of a Wilms' tumor with hitherto undescribed ultrastructural and histochemical features is presented. The unique features conform structurally, and to some extent chemically to autophagosomes, which occur in similar abundance only in granular cell myoblastoma, recently considered to be derived from neural elements. The implication of this common structural feature readdresses attention to the work of Masson, who originally theorized a neurectodermal origin for the Wilms' tumor."}
{"id": "PMID:231385", "title": "Bronchiolo-alveolar carcinoma with nodal metastases. An ultrastructural study.", "content": "A case of bronchiolo-alveolar carcinoma of the lung was studied by light and electron microscopy. Type II granular pneumocytes were seen in the lymph node metastases of the tumor, a finding not reported previously. We feel that the presence of these cells in metastatic foci indicates their neoplastic nature, and provides evidence that bronchiolo-alveolar carcinoma arises from type II cells.", "contents": "Bronchiolo-alveolar carcinoma with nodal metastases. An ultrastructural study. A case of bronchiolo-alveolar carcinoma of the lung was studied by light and electron microscopy. Type II granular pneumocytes were seen in the lymph node metastases of the tumor, a finding not reported previously. We feel that the presence of these cells in metastatic foci indicates their neoplastic nature, and provides evidence that bronchiolo-alveolar carcinoma arises from type II cells."}
{"id": "PMID:231387", "title": "Malignant mixed tumor of the lacrimal gland.", "content": "This paper reports a case of carcinoma arising in a benign mixed tumor of lacrimal gland following multiple recurrences. The patient had eight recurrences of the benign lesion and after 32 years developed an adenocarcinoma associated with recurrent nodules of still recognizable benign mixed tumor. The literature on malignant mixed tumors of the lacrimal gland is reviewed noting the confusion in diagnostic terminology in early reports. Our patient illustrates the resemblance between malignant mixed tumor (carcinoma arising in pleomorphic adenoma) of lacrimal and salivary gland both clinically and pathologically.", "contents": "Malignant mixed tumor of the lacrimal gland. This paper reports a case of carcinoma arising in a benign mixed tumor of lacrimal gland following multiple recurrences. The patient had eight recurrences of the benign lesion and after 32 years developed an adenocarcinoma associated with recurrent nodules of still recognizable benign mixed tumor. The literature on malignant mixed tumors of the lacrimal gland is reviewed noting the confusion in diagnostic terminology in early reports. Our patient illustrates the resemblance between malignant mixed tumor (carcinoma arising in pleomorphic adenoma) of lacrimal and salivary gland both clinically and pathologically."}
{"id": "PMID:231396", "title": "[A case of Hodgkin's disease with thrombocytopenic purpura, polyneuritis, and cytomegalovirus pneumopathy (author's transl)].", "content": "A patient with Hodgkins disease developed successively, a thrombocytopenic purpura, a polyneuristis and a pneumopathy, during a period of remission, and over a period of time lasting 3 months. The authors discuss the possibility of cytomegalovirus being the causative agent.", "contents": "[A case of Hodgkin's disease with thrombocytopenic purpura, polyneuritis, and cytomegalovirus pneumopathy (author's transl)]. A patient with Hodgkins disease developed successively, a thrombocytopenic purpura, a polyneuristis and a pneumopathy, during a period of remission, and over a period of time lasting 3 months. The authors discuss the possibility of cytomegalovirus being the causative agent."}
{"id": "PMID:231398", "title": "[Comparative value of temperature marker and neutralization test for subtyping of herpes simplex viruses (author's transl)].", "content": "Two methods for the differentiation of herpes simplex virus (HSV)--rct and neutralization by specific antisera--have been applied to 8 prototype strains and 105 strains isolated from various clinical cases. The evaluation of the II/I index allows to choose the most specific rabbit antisera. The rct 40 degrees 3 C marker test gives comparable results for HSV grown in RK13 and human fibroblasts as well; it is in agreement with the immunological test in 48% of the cases. The delta tc values used to express the immunological typing allow to differentiate 76% of the strains (types 1 and 2). The others (24%) are equally neutralized by both specific antisera; they represent \"intermediate\" strains. The infection of man and animal by HSV (type 1, 2 or \"intermediate\") also produces heterospecific antibodies in variable amount. From clinical and immunological data rises the hypothesis that \"intermediate\" strains derive from HSV1 strains by antigenic variation during a persistent infection.", "contents": "[Comparative value of temperature marker and neutralization test for subtyping of herpes simplex viruses (author's transl)]. Two methods for the differentiation of herpes simplex virus (HSV)--rct and neutralization by specific antisera--have been applied to 8 prototype strains and 105 strains isolated from various clinical cases. The evaluation of the II/I index allows to choose the most specific rabbit antisera. The rct 40 degrees 3 C marker test gives comparable results for HSV grown in RK13 and human fibroblasts as well; it is in agreement with the immunological test in 48% of the cases. The delta tc values used to express the immunological typing allow to differentiate 76% of the strains (types 1 and 2). The others (24%) are equally neutralized by both specific antisera; they represent \"intermediate\" strains. The infection of man and animal by HSV (type 1, 2 or \"intermediate\") also produces heterospecific antibodies in variable amount. From clinical and immunological data rises the hypothesis that \"intermediate\" strains derive from HSV1 strains by antigenic variation during a persistent infection."}
{"id": "PMID:231403", "title": "Endogenous prostaglandin synthesis and the control of lymphocyte function.", "content": "Prostaglandins serve an important regulatory role in immune responses. Much of their activity seems to involve regulating the early stages of lymphocyte or macrophage activation. Besides the capacity of prostaglandins to control lymphocyte activation directly by blocking transformation, at least one type, PGE2 can induce a class of glass-adherent T-cells to produce a suppressive peptide in vitro. The data we have obtained suggest the existence of a feedback loop in which PG production by an activated T-cell serves as the signal that induces a second T-cell to release a suppressor peptide. This peptide can then regulate the ability of the activated T-cell to pass through the cell cycle. Other examples of feedback loops have recently been postulated or shown to exist among immunocompetent cells. It remains to be shown how these various regulatory loops combine to form the integrated network that modulates immunoresponsiveness.", "contents": "Endogenous prostaglandin synthesis and the control of lymphocyte function. Prostaglandins serve an important regulatory role in immune responses. Much of their activity seems to involve regulating the early stages of lymphocyte or macrophage activation. Besides the capacity of prostaglandins to control lymphocyte activation directly by blocking transformation, at least one type, PGE2 can induce a class of glass-adherent T-cells to produce a suppressive peptide in vitro. The data we have obtained suggest the existence of a feedback loop in which PG production by an activated T-cell serves as the signal that induces a second T-cell to release a suppressor peptide. This peptide can then regulate the ability of the activated T-cell to pass through the cell cycle. Other examples of feedback loops have recently been postulated or shown to exist among immunocompetent cells. It remains to be shown how these various regulatory loops combine to form the integrated network that modulates immunoresponsiveness."}
{"id": "PMID:231404", "title": "Prostaglandins and their regulation in rheumatoid inflammation.", "content": "Prostaglandins, especially PGE2 and PGI2, appear to participate in the development of inflammatory reactions. While these PGs may act to promote inflammation, they may also inhibit immune reactions; this effect is largely related to stimulation of adenylate cyclase. Human rheumatoid synovial tissue explants and derived adherent synovial cells (ASC) in vitro produce large amounts of PG, primarily PGE2, which may participate in the pathogenesis of rheumatoid inflammation and promote the osteoclastic resorption of juxtaarticular bone. Rheumatoid synovial organ cultures are unusual in that they derive a significant proportion of archidonic acid substrate for the PGE2 synthesis from triglycerides, while ASC utilize primarily phospholipids. Aspirin-like, nonsteroidal anti-inflammatory drugs inhibit PGE2 synthesis by rheumatoid synovial organ cultures at concentrations similar to those achieved in plasma during therapy. Glucocorticoids are also potent inhibitors of PGE2 synthesis, and evidence from experiments with tissue labeled with 1-[14C]arachidonic acid indicates that glucocorticoids do not act to inhibit arachidonic acid release, as has been postulated for other tissues. Human peripheral blood mononuclear cells produce a factor (MCF) that regularly stimulates the production of PGE2 and collagenase from resting ASC often by over 100-fold. The MCF appears to be produced by monocytes, and its production by monocytes is enhanced by lectin-stimulated T-cells. The ability of ASC to respond to exogenous PGE2 stimulation of cAMP synthesis is inhibited or stimulated by factors that increase or decrease PGE2 levels, respectively, in the cultures. The MCF augments the responsiveness of cAMP response to PGE2 in indomethacin-treated cultures. These in vitro experiments suggest that the pathogenesis of rheumatoid inflammation involves interactions between monocyte-macrophages, lymphocytes, and synovial cells regulating the production of PGE2, cAMP, and other factors.", "contents": "Prostaglandins and their regulation in rheumatoid inflammation. Prostaglandins, especially PGE2 and PGI2, appear to participate in the development of inflammatory reactions. While these PGs may act to promote inflammation, they may also inhibit immune reactions; this effect is largely related to stimulation of adenylate cyclase. Human rheumatoid synovial tissue explants and derived adherent synovial cells (ASC) in vitro produce large amounts of PG, primarily PGE2, which may participate in the pathogenesis of rheumatoid inflammation and promote the osteoclastic resorption of juxtaarticular bone. Rheumatoid synovial organ cultures are unusual in that they derive a significant proportion of archidonic acid substrate for the PGE2 synthesis from triglycerides, while ASC utilize primarily phospholipids. Aspirin-like, nonsteroidal anti-inflammatory drugs inhibit PGE2 synthesis by rheumatoid synovial organ cultures at concentrations similar to those achieved in plasma during therapy. Glucocorticoids are also potent inhibitors of PGE2 synthesis, and evidence from experiments with tissue labeled with 1-[14C]arachidonic acid indicates that glucocorticoids do not act to inhibit arachidonic acid release, as has been postulated for other tissues. Human peripheral blood mononuclear cells produce a factor (MCF) that regularly stimulates the production of PGE2 and collagenase from resting ASC often by over 100-fold. The MCF appears to be produced by monocytes, and its production by monocytes is enhanced by lectin-stimulated T-cells. The ability of ASC to respond to exogenous PGE2 stimulation of cAMP synthesis is inhibited or stimulated by factors that increase or decrease PGE2 levels, respectively, in the cultures. The MCF augments the responsiveness of cAMP response to PGE2 in indomethacin-treated cultures. These in vitro experiments suggest that the pathogenesis of rheumatoid inflammation involves interactions between monocyte-macrophages, lymphocytes, and synovial cells regulating the production of PGE2, cAMP, and other factors."}
{"id": "PMID:231410", "title": "[Effects of a phytohemagglutinin extract on growth, nitrogen digestibility and the activity of invertase and (Na+-K+)-ATPase in the intestinal mucosa of the rat].", "content": "A phytohemagglutinin extract is prepared from raw kidney beans (Phaseolus vulgaris) and incorporated at a level of 1% (dry matter) in the diet of young growing rats. Beside a decrease of feed intakes, the main effects of the experimental diet are the following : growth depression, decrease of dry matter and protein digestibility and hypoglycemia. Biological value, organs weight (liver, kidneys, spleen) did not change significantly. The hemagglutinin extract induces an inhibition of saccharase activity whereas (Na+-K+)-ATPase remains unchanged. Growth depressing effect may be due to an alteration of hydrolysis and absorption mechanisms at the level of brush border of enterocytes.", "contents": "[Effects of a phytohemagglutinin extract on growth, nitrogen digestibility and the activity of invertase and (Na+-K+)-ATPase in the intestinal mucosa of the rat]. A phytohemagglutinin extract is prepared from raw kidney beans (Phaseolus vulgaris) and incorporated at a level of 1% (dry matter) in the diet of young growing rats. Beside a decrease of feed intakes, the main effects of the experimental diet are the following : growth depression, decrease of dry matter and protein digestibility and hypoglycemia. Biological value, organs weight (liver, kidneys, spleen) did not change significantly. The hemagglutinin extract induces an inhibition of saccharase activity whereas (Na+-K+)-ATPase remains unchanged. Growth depressing effect may be due to an alteration of hydrolysis and absorption mechanisms at the level of brush border of enterocytes."}
{"id": "PMID:231411", "title": "Treatment of hepatocellular carcinoma with associated cirrhosis.", "content": "During the recent 10 years, 105 patients with hepatocellular carcinoma were admitted to our clinic. Seventy of them had an associated cirrhosis of the liver. The therapeutic results of these 70 patients were analyzed according to the mode of treatment. The mean survival periods after admission were as follows; No cancer treatment group (12 patients) 79 days, Chemotherapy group regardless of the mode of administration (25 patients) 97 days, Hepatic artery ligation with chemotherapy group (16 patients) 197 days. Hepatic resection was carried out in 17 patients; partial hepatectomy in 5, left lateral segmentectomy in 1, left lobectomy in 3, and right lobectomy in 8. The 50% survival period of all the hepatectomized patients was 8.5 months. Seven patients are living 5 months to 3 years after operation. Five patients died of recurrence of hepatoma between 4 months and 3 years and 2 months postoperatively. Five individuals died of causes related to the operation; two hepatic failure, two fatal infection, and one massive haemorrhage from acute duodenal ulcer. The results indicated that hepatic resection, from partial to extensive, might be possible even in patients with associated cirrhosis but more exact criteria are mandatory in selecting patients for major hepatic resection. Hepatic artery ligation with chemotherapy should be the first choice for those with nonresectable hepatoma. Continuous infusion of oncolytic agents into the hepatic artery may be considered for those in whom arterial ligation is contraindicated.", "contents": "Treatment of hepatocellular carcinoma with associated cirrhosis. During the recent 10 years, 105 patients with hepatocellular carcinoma were admitted to our clinic. Seventy of them had an associated cirrhosis of the liver. The therapeutic results of these 70 patients were analyzed according to the mode of treatment. The mean survival periods after admission were as follows; No cancer treatment group (12 patients) 79 days, Chemotherapy group regardless of the mode of administration (25 patients) 97 days, Hepatic artery ligation with chemotherapy group (16 patients) 197 days. Hepatic resection was carried out in 17 patients; partial hepatectomy in 5, left lateral segmentectomy in 1, left lobectomy in 3, and right lobectomy in 8. The 50% survival period of all the hepatectomized patients was 8.5 months. Seven patients are living 5 months to 3 years after operation. Five patients died of recurrence of hepatoma between 4 months and 3 years and 2 months postoperatively. Five individuals died of causes related to the operation; two hepatic failure, two fatal infection, and one massive haemorrhage from acute duodenal ulcer. The results indicated that hepatic resection, from partial to extensive, might be possible even in patients with associated cirrhosis but more exact criteria are mandatory in selecting patients for major hepatic resection. Hepatic artery ligation with chemotherapy should be the first choice for those with nonresectable hepatoma. Continuous infusion of oncolytic agents into the hepatic artery may be considered for those in whom arterial ligation is contraindicated."}
{"id": "PMID:231413", "title": "Temperature-sensitive 6-aminopenicillanic acid-resistant mutants of Escherichia coli.", "content": "Wild-type Escherichia coli cells became spherical in the presence of low concentrations of 6-aminopenicillanic acid (APA). Higher concentrations of APA caused inhibition of cell division (filamentation) and lysis. Spontaneous temperature-sensitive APA-resistant mutants were isolated and characterized. These mutants also possessed increased resistance to mecillinam but not to benzylpenicillin, ampicillin, and cephaloridine. They formed round or pleomorphic cells at the nonpermissive temperature and possessed thermolabile penicillin-binding protein 2 activity. Temperature-resistant revertants of these mutants had normal rod-shaped morphology, normal levels of sensitivity to APA and mecillinam, and thermostable penicillin-binding protein 2 activity. The mutation conferring APA resistance cotransduced with lip and mapped, therefore, close to 14 min on the E. coli linkage map. APA appears to be more specific than mecillinam as a selective agent for the isolation of penicillin-binding protein 2 mutants.", "contents": "Temperature-sensitive 6-aminopenicillanic acid-resistant mutants of Escherichia coli. Wild-type Escherichia coli cells became spherical in the presence of low concentrations of 6-aminopenicillanic acid (APA). Higher concentrations of APA caused inhibition of cell division (filamentation) and lysis. Spontaneous temperature-sensitive APA-resistant mutants were isolated and characterized. These mutants also possessed increased resistance to mecillinam but not to benzylpenicillin, ampicillin, and cephaloridine. They formed round or pleomorphic cells at the nonpermissive temperature and possessed thermolabile penicillin-binding protein 2 activity. Temperature-resistant revertants of these mutants had normal rod-shaped morphology, normal levels of sensitivity to APA and mecillinam, and thermostable penicillin-binding protein 2 activity. The mutation conferring APA resistance cotransduced with lip and mapped, therefore, close to 14 min on the E. coli linkage map. APA appears to be more specific than mecillinam as a selective agent for the isolation of penicillin-binding protein 2 mutants."}
{"id": "PMID:231414", "title": "Efficiency of several micro-fiber glass filters for recovery of poliovirus from tape water.", "content": "Micro-fiber glass filters from Gelman, Filterite, Johns-Manville, and Whatman were compared with Millipore membrane filters on the basis of their virus adsorbancy, flow rate, clogging resistance, and virus concentration efficiency by using tap water at 2 nephelometric turbidity units. As virus adsorbants the Johns-Manville D39, Filterite 0.25-micron, Filterite 0.45-micron, and Millipore 0.45-micron filters were the most efficient, retaining more than 99% of the added virus in water at pH 3.5 and 0.0005 M aluminum chloride. The Johns-Manville D79 and D49 filters retained 92 and 96% of the virus, respectively, whereas the Whatman GF-D, Whatman GF-F, Gelman A-E, and Millipore AP-20 filters retained only 28, 78, 56, and 34% of the virus, respectively. The best flow rate and clogging resistance were obtained with the Johns-Manville D79 filter or with this filter acting as a prefilter to the Johns-Manville D49, Johns-Manville D39, or Filterite 0.45-micron filter. Finally, poliovirus experimentally seeded in 20 liters of tape water was recovered from Johns-Manville D79-Johns-Manville D39 or Johns-Manville D79-Filterite 0.45 micron 142-mm filter combinations was a efficiencies of 86 and 85%, respectively.", "contents": "Efficiency of several micro-fiber glass filters for recovery of poliovirus from tape water. Micro-fiber glass filters from Gelman, Filterite, Johns-Manville, and Whatman were compared with Millipore membrane filters on the basis of their virus adsorbancy, flow rate, clogging resistance, and virus concentration efficiency by using tap water at 2 nephelometric turbidity units. As virus adsorbants the Johns-Manville D39, Filterite 0.25-micron, Filterite 0.45-micron, and Millipore 0.45-micron filters were the most efficient, retaining more than 99% of the added virus in water at pH 3.5 and 0.0005 M aluminum chloride. The Johns-Manville D79 and D49 filters retained 92 and 96% of the virus, respectively, whereas the Whatman GF-D, Whatman GF-F, Gelman A-E, and Millipore AP-20 filters retained only 28, 78, 56, and 34% of the virus, respectively. The best flow rate and clogging resistance were obtained with the Johns-Manville D79 filter or with this filter acting as a prefilter to the Johns-Manville D49, Johns-Manville D39, or Filterite 0.45-micron filter. Finally, poliovirus experimentally seeded in 20 liters of tape water was recovered from Johns-Manville D79-Johns-Manville D39 or Johns-Manville D79-Filterite 0.45 micron 142-mm filter combinations was a efficiencies of 86 and 85%, respectively."}
{"id": "PMID:231415", "title": "Immunological evidence for an ACTH-like antigen in the nervous ganglion of a protochordate Ciona intestinalis (Ascidiacea).", "content": "Nervous fibers and neurons containing an ACTH-like antigen could be demonstrated in the nervous ganglion of a Protochordate Ciona intestinalis, using indirect immunofluorescence and anti (17-39)-ACTH and anti (25-39)-ACTH antisera.", "contents": "Immunological evidence for an ACTH-like antigen in the nervous ganglion of a protochordate Ciona intestinalis (Ascidiacea). Nervous fibers and neurons containing an ACTH-like antigen could be demonstrated in the nervous ganglion of a Protochordate Ciona intestinalis, using indirect immunofluorescence and anti (17-39)-ACTH and anti (25-39)-ACTH antisera."}
{"id": "PMID:231417", "title": "[Structure of calf rotavirus. 1. Hydrodynamic and electron microscopic parameters of the virus].", "content": "Rotavirus was isolated from the faeces of calves afflicted with diarrhoea and purified. Isolation was preceded by chloroform treatment, oxide wax A-precipitation, as well as differential and density gradient centrifugation. Virus density in CsCl solution was 1.38 +/- 0.01 g/ml. Cell culture virus prepared without chloroform (Nebraska-type isolation) would be 1.37 +/- 0.01 g/ml in density, for comparison. The mean capsid diameters measured were 55 nm and 60 nm, sedimentation coefficents being between 450 and 478 S. The mean core diameter was 40 nm. Structure of capsid is discussed.", "contents": "[Structure of calf rotavirus. 1. Hydrodynamic and electron microscopic parameters of the virus]. Rotavirus was isolated from the faeces of calves afflicted with diarrhoea and purified. Isolation was preceded by chloroform treatment, oxide wax A-precipitation, as well as differential and density gradient centrifugation. Virus density in CsCl solution was 1.38 +/- 0.01 g/ml. Cell culture virus prepared without chloroform (Nebraska-type isolation) would be 1.37 +/- 0.01 g/ml in density, for comparison. The mean capsid diameters measured were 55 nm and 60 nm, sedimentation coefficents being between 450 and 478 S. The mean core diameter was 40 nm. Structure of capsid is discussed."}
{"id": "PMID:231420", "title": "A role of red cell pyrimidine 5'-nucleotidase in experimental lead poisoning.", "content": "Intravenous administration of lead acetate to rabbits for 10 weeks at 2 week intervals resulted in significantly elevated blood lead levels, slight anemia with marked microspherocytosis and moderate basophilic stippling, and marked depression of red cell delta-aminolevulinic acid (ALA) dehydratase activity. However the decrease in red cell pyrimidine 5'-nucleotidase (P5N) activity was slight when compared to the red cell P5N activity of comparable reticulocyte-rich blood, and intracellular accumulation of pyrimidine nucleotides could not be demonstrated. In the in vitro inhibition test the same degree of inhibition of red cell P5N activity seen in hereditary red cell P5N deficiency was obtained by using a lead concentration 200--400 times higher than the lead levels detected in human plumbism. Most importantly, there were no differences in the lead-induced inhibition of human and rabbit red cell P5N. From the results of the in vitro inhibition test, lead-induced red cell P5N deficiency appears to be one of several pathogenic mechanisms in chronic lead exposure associated with the accumulation of lead in bone marrow. A decrease in rec cell P5N activity could not be demonstrated despite the marked depression in red cell ALA dehydratase activity, and slight anemia with marked microspherocytosis and moderate basophilic stippling in this experiment. These results suggest that lead affects red cells at multiple metabolic loci.", "contents": "A role of red cell pyrimidine 5'-nucleotidase in experimental lead poisoning. Intravenous administration of lead acetate to rabbits for 10 weeks at 2 week intervals resulted in significantly elevated blood lead levels, slight anemia with marked microspherocytosis and moderate basophilic stippling, and marked depression of red cell delta-aminolevulinic acid (ALA) dehydratase activity. However the decrease in red cell pyrimidine 5'-nucleotidase (P5N) activity was slight when compared to the red cell P5N activity of comparable reticulocyte-rich blood, and intracellular accumulation of pyrimidine nucleotides could not be demonstrated. In the in vitro inhibition test the same degree of inhibition of red cell P5N activity seen in hereditary red cell P5N deficiency was obtained by using a lead concentration 200--400 times higher than the lead levels detected in human plumbism. Most importantly, there were no differences in the lead-induced inhibition of human and rabbit red cell P5N. From the results of the in vitro inhibition test, lead-induced red cell P5N deficiency appears to be one of several pathogenic mechanisms in chronic lead exposure associated with the accumulation of lead in bone marrow. A decrease in rec cell P5N activity could not be demonstrated despite the marked depression in red cell ALA dehydratase activity, and slight anemia with marked microspherocytosis and moderate basophilic stippling in this experiment. These results suggest that lead affects red cells at multiple metabolic loci."}
{"id": "PMID:231421", "title": "[Ocular myopathy, Kiloh-Nevin type; study of a case with histochemical and ultrastructural changes].", "content": "A non-familiar case of Kiloh-Nevin ocular myopathy with important histochemical and ultrastructural abnormalities is reported. The patient, a 43 year-old male presented with 10 year long, pregressive ocular ophtalmoplegia, myasthenic symptoms and severe muscular pain, an uncommon finding in this type of myopathy. The histochemical study showed muscular atrophy, mainly in type I fibres and a great amount of ragged-red fibres. Of particular interest, in this case, was the ultrastructural finding of severe mitochondrial abnormalities with a lot of inclusions in the cristae matrix; nevertheless these changes are not specific. The authors suggest a possible abnormality in the neuro-muscular transmission system and a genetically controlled enzimatic factor as responsible for the aethiology and pathogenesis of the Kiloh-Nevin ocular myopathy.", "contents": "[Ocular myopathy, Kiloh-Nevin type; study of a case with histochemical and ultrastructural changes]. A non-familiar case of Kiloh-Nevin ocular myopathy with important histochemical and ultrastructural abnormalities is reported. The patient, a 43 year-old male presented with 10 year long, pregressive ocular ophtalmoplegia, myasthenic symptoms and severe muscular pain, an uncommon finding in this type of myopathy. The histochemical study showed muscular atrophy, mainly in type I fibres and a great amount of ragged-red fibres. Of particular interest, in this case, was the ultrastructural finding of severe mitochondrial abnormalities with a lot of inclusions in the cristae matrix; nevertheless these changes are not specific. The authors suggest a possible abnormality in the neuro-muscular transmission system and a genetically controlled enzimatic factor as responsible for the aethiology and pathogenesis of the Kiloh-Nevin ocular myopathy."}
{"id": "PMID:231422", "title": "[Reaction of the fibrose eyeball covering upon the suture material synthetic and absorbable \"Dexon\". (Experimental study) (author's transl)].", "content": "The present paper deals with the results of 20 eyes of experimentally operated laboratory animals, whose perforating wounds (of cornea and those of sclerocorneal region) have been suturated with a new type of absorbable synthetic suture material \"Dexon\" thickness being 6-0. The synthetic absorbable suture material \"Dexon\" is made of polyglycol acid, and it has been introduced to market by the firm Davis and Geck (U.S.A.). The inflammatory tissue reaction to the presence of the suture material \"Dexon\" is prominent and can by compared to the reaction to chromic resorbable suture materials (catgut or collagen). The suture material \"Dexon\" start to resorb in the course of the 2nd-3rd weeks after operation. The suture material \"Dexon\" can be used at an advantage in the operation where it is possible to cover the knots by a conjuctival lobe (in sclerocorneal region or in strabismus surgery) in this way the tendency to overgrowing of epithelial cells along the suture channels can be prevented. The \"Dexon\" material is sufficiently flexible and firm and has no antigenic properties, therefore it appears very prospective for ophthalmosurgery.", "contents": "[Reaction of the fibrose eyeball covering upon the suture material synthetic and absorbable \"Dexon\". (Experimental study) (author's transl)]. The present paper deals with the results of 20 eyes of experimentally operated laboratory animals, whose perforating wounds (of cornea and those of sclerocorneal region) have been suturated with a new type of absorbable synthetic suture material \"Dexon\" thickness being 6-0. The synthetic absorbable suture material \"Dexon\" is made of polyglycol acid, and it has been introduced to market by the firm Davis and Geck (U.S.A.). The inflammatory tissue reaction to the presence of the suture material \"Dexon\" is prominent and can by compared to the reaction to chromic resorbable suture materials (catgut or collagen). The suture material \"Dexon\" start to resorb in the course of the 2nd-3rd weeks after operation. The suture material \"Dexon\" can be used at an advantage in the operation where it is possible to cover the knots by a conjuctival lobe (in sclerocorneal region or in strabismus surgery) in this way the tendency to overgrowing of epithelial cells along the suture channels can be prevented. The \"Dexon\" material is sufficiently flexible and firm and has no antigenic properties, therefore it appears very prospective for ophthalmosurgery."}
{"id": "PMID:231424", "title": "Experimental oxalate urolith formation in rats.", "content": "Urinary calculi composed of calcium oxalate were produced in male hooded Wistar rats fed a vitamin B6 deficient diet over 16 weeks. This basic diet was modified by doubling the phosphate content or loading with vitamin C or D3 in three treatment groups. The number of rats developing oxalate stones was not altered by the addition of vitamin D3 or phosphate, but there was a significant increase in total weight of stone formed and histological evidence of extensive renal damage in rats on the high vitamin D3 diet. The addition of vitamin C to the vitamin B6 deficient rats resulted in a reduction in the number of rats with uroliths and a fall in urinary oxalate excretion, while similarly loaded vitamin B6 supplemented controls were free of oxalate calculi. It is concluded that the oxalate urolithiasis induced by vitamin B6 deficiency was exacerbated by added vitamin D3 and reduced by vitamin C.", "contents": "Experimental oxalate urolith formation in rats. Urinary calculi composed of calcium oxalate were produced in male hooded Wistar rats fed a vitamin B6 deficient diet over 16 weeks. This basic diet was modified by doubling the phosphate content or loading with vitamin C or D3 in three treatment groups. The number of rats developing oxalate stones was not altered by the addition of vitamin D3 or phosphate, but there was a significant increase in total weight of stone formed and histological evidence of extensive renal damage in rats on the high vitamin D3 diet. The addition of vitamin C to the vitamin B6 deficient rats resulted in a reduction in the number of rats with uroliths and a fall in urinary oxalate excretion, while similarly loaded vitamin B6 supplemented controls were free of oxalate calculi. It is concluded that the oxalate urolithiasis induced by vitamin B6 deficiency was exacerbated by added vitamin D3 and reduced by vitamin C."}
{"id": "PMID:231426", "title": "Cyclic nucleotide metabolism in tumours.", "content": "Many hormones act by combining with cell surface receptors and stimulating adenylate cyclase activity. The cyclic AMP generated is the mediator of a number of cellular metabolic processes. Other processes may be influenced by changes in cyclic GMP levels. Although much evidence from cultured cells suggested that low cellular levels of cyclic AMP and high levels of cyclic GMP are a feature of rapid cell growth and of malignant transformation, review of the data reveals many inconsistencies. Thus in established tumours growing in vivo, for example, cyclic AMP levels appear to be unrelated to tumour growth rates. It seems that tumour cell cyclic AMP is more likely concerned with the regulation of tumour cell function than of growth. This would have implications for therapy, in that drugs which influence cyclic nucleotide metabolism could influence tumour cell function. The control of cyclic nucleotide production in normal and tumour cells is discussed, together with the possible ways in which abnormalities of this may occur.", "contents": "Cyclic nucleotide metabolism in tumours. Many hormones act by combining with cell surface receptors and stimulating adenylate cyclase activity. The cyclic AMP generated is the mediator of a number of cellular metabolic processes. Other processes may be influenced by changes in cyclic GMP levels. Although much evidence from cultured cells suggested that low cellular levels of cyclic AMP and high levels of cyclic GMP are a feature of rapid cell growth and of malignant transformation, review of the data reveals many inconsistencies. Thus in established tumours growing in vivo, for example, cyclic AMP levels appear to be unrelated to tumour growth rates. It seems that tumour cell cyclic AMP is more likely concerned with the regulation of tumour cell function than of growth. This would have implications for therapy, in that drugs which influence cyclic nucleotide metabolism could influence tumour cell function. The control of cyclic nucleotide production in normal and tumour cells is discussed, together with the possible ways in which abnormalities of this may occur."}
{"id": "PMID:231427", "title": "Spinal canal stenosis in adult with hypophosphataemic vitamin D-resistant rickets.", "content": "A case is described of a 55-year-old male with hypophosphataemic vitamin D-resistant rickets, who presented with long-standing back pain and paraesthesiae in both legs considered to be due to osteoid encroachment on an already narrow spinal canal. Marked symptomatic improvement has followed extensive lumbar laminectomy.", "contents": "Spinal canal stenosis in adult with hypophosphataemic vitamin D-resistant rickets. A case is described of a 55-year-old male with hypophosphataemic vitamin D-resistant rickets, who presented with long-standing back pain and paraesthesiae in both legs considered to be due to osteoid encroachment on an already narrow spinal canal. Marked symptomatic improvement has followed extensive lumbar laminectomy."}
{"id": "PMID:231428", "title": "An immunofluorescence diagnostic test for avian infectious laryngotracheitis.", "content": "An antiserum to a recent field isolate of infectious laryngotracheitis virus was conjugated with fluorescein isothiocyanate and used to detect viral antigen to infected chorioallantoic membranes and trachael epithelium by the direct fluorescent antibody technique. In experimentally infected birds, viral antigen was detected with the fluorescent antibody technique from 2 to 14 days post-inoculation but histological evidence of tracheitis was only observed from day three to day ten. The fluorescent antibody test detected 22 of 23 histologically confirmed cases of ILT and was more accurate than virus isolation when used in the diagnosis of respiratory disease from field outbreaks. It was concluded that the speed, accuracy and sensitivity of the fluorescent antibody technique make it a useful tool in the diagnosis of infectious laryngotracheitis.", "contents": "An immunofluorescence diagnostic test for avian infectious laryngotracheitis. An antiserum to a recent field isolate of infectious laryngotracheitis virus was conjugated with fluorescein isothiocyanate and used to detect viral antigen to infected chorioallantoic membranes and trachael epithelium by the direct fluorescent antibody technique. In experimentally infected birds, viral antigen was detected with the fluorescent antibody technique from 2 to 14 days post-inoculation but histological evidence of tracheitis was only observed from day three to day ten. The fluorescent antibody test detected 22 of 23 histologically confirmed cases of ILT and was more accurate than virus isolation when used in the diagnosis of respiratory disease from field outbreaks. It was concluded that the speed, accuracy and sensitivity of the fluorescent antibody technique make it a useful tool in the diagnosis of infectious laryngotracheitis."}
{"id": "PMID:231433", "title": "Comparison of 4 serological tests--complement fixation, neutralization, fluorescent antibody to membrane antigen and immune adherence hemagglutination--for assay of antibody to varicella-zoster (V-Z) virus.", "content": "Four tests for antibody to varicella-zoster (V-Z) virus were compared; these were tests of complement fixation (CF), neutralization (NT), fluorescent antibody to membrane antigen (FAMA) and immune adherence hemagglutination (IAHA). Fifty-two sera from patients with varicella and zoster and from recipients of live varicella vaccine were examined by the 4 tests. The CF test was least sensitive, but the antibody titers by the NT, FAMA and IAHA tests were roughly comparable. The IAHA test was the simplest and fastest to perform, and appeared suitable for routine serological assay to V-Z virus. The correlation between the IAHA antibody titer and susceptibility of individuals to clinical varicella was investigated retrospectively using sera obtained during 2 outbreaks of varicella in an institution for children, where all the unvaccinated children had developed varicella symptoms. Most of the 25 pre-exposure sera from unvaccinated children examined by the IAHA test had tiers of less than 1:2. In contrast, all the 23 sera from vaccinated children who did not develop varicella had detectable antibody titers of 1:2 to 1:64. These results indicate that the IAHA titer reflects the susceptibility or resistance of individuals to clinical varicella.", "contents": "Comparison of 4 serological tests--complement fixation, neutralization, fluorescent antibody to membrane antigen and immune adherence hemagglutination--for assay of antibody to varicella-zoster (V-Z) virus. Four tests for antibody to varicella-zoster (V-Z) virus were compared; these were tests of complement fixation (CF), neutralization (NT), fluorescent antibody to membrane antigen (FAMA) and immune adherence hemagglutination (IAHA). Fifty-two sera from patients with varicella and zoster and from recipients of live varicella vaccine were examined by the 4 tests. The CF test was least sensitive, but the antibody titers by the NT, FAMA and IAHA tests were roughly comparable. The IAHA test was the simplest and fastest to perform, and appeared suitable for routine serological assay to V-Z virus. The correlation between the IAHA antibody titer and susceptibility of individuals to clinical varicella was investigated retrospectively using sera obtained during 2 outbreaks of varicella in an institution for children, where all the unvaccinated children had developed varicella symptoms. Most of the 25 pre-exposure sera from unvaccinated children examined by the IAHA test had tiers of less than 1:2. In contrast, all the 23 sera from vaccinated children who did not develop varicella had detectable antibody titers of 1:2 to 1:64. These results indicate that the IAHA titer reflects the susceptibility or resistance of individuals to clinical varicella."}
{"id": "PMID:231434", "title": "Epidemiological and virological studies on outbreaks of acute gastroenteritis associated with rotavirus in primary schools in Osaka.", "content": "There have been three recent outbreaks of acute gastroenteritis in primary schools in Osaka prefecture caused by rotavirus: one in a school (TA) in April, 1974 and two in two other schools (TE and K) in May 1975. The morbidity from the disease was 2.4--15.8% for all age groups in the schools, and 20.1--34.1% for a certain age group. The disease lasted for 4 (K) to 14 days (TE). The first cases in schools TA and TE were followed by successive cases. The main clinical symptoms were higher frequencies of diarrhea (68--71.4%) and fever (78%) than in winter vomiting disease. There was no difference in the incidences of the disease in boys and girls. From observation on the disease in individual families, the incubation period seemed to be 3 days. Using paired sera and Neonatal Calf Diarrhea Virus (NCDV) as antigen, positive seroconversion was demonstrated by the complement fixation test and marked seroconversion by the indirect fluorescent antibody technique. With these techniques, specific antibody to NCDV was detectable in the sera from an early stage of illness. Rotavirus was found on electron microscopic examination of some fecal specimens of patients in TA, but not in those of patients in TE or K, although adenovirus was isolated from one patient. A serological survey of healthy children aged 0 to 12 showed that rotavirus is a common virus in Osaka.", "contents": "Epidemiological and virological studies on outbreaks of acute gastroenteritis associated with rotavirus in primary schools in Osaka. There have been three recent outbreaks of acute gastroenteritis in primary schools in Osaka prefecture caused by rotavirus: one in a school (TA) in April, 1974 and two in two other schools (TE and K) in May 1975. The morbidity from the disease was 2.4--15.8% for all age groups in the schools, and 20.1--34.1% for a certain age group. The disease lasted for 4 (K) to 14 days (TE). The first cases in schools TA and TE were followed by successive cases. The main clinical symptoms were higher frequencies of diarrhea (68--71.4%) and fever (78%) than in winter vomiting disease. There was no difference in the incidences of the disease in boys and girls. From observation on the disease in individual families, the incubation period seemed to be 3 days. Using paired sera and Neonatal Calf Diarrhea Virus (NCDV) as antigen, positive seroconversion was demonstrated by the complement fixation test and marked seroconversion by the indirect fluorescent antibody technique. With these techniques, specific antibody to NCDV was detectable in the sera from an early stage of illness. Rotavirus was found on electron microscopic examination of some fecal specimens of patients in TA, but not in those of patients in TE or K, although adenovirus was isolated from one patient. A serological survey of healthy children aged 0 to 12 showed that rotavirus is a common virus in Osaka."}
{"id": "PMID:231437", "title": "Marek's disease virus and herpesvirus of turkey noninfective to chickens, obtained by repeated in vitro passages.", "content": "The relation between the passage level of Marek's disease virus, C2 strain, and of herpesvirus of turkey (HVT), O1 strain, in cell culture and the level of the serological response of chickens to these viruses was examined. In both cases the immune response of chickens to these viruses decreased with increase in the number of in vitro passages of virus. Virus was not recovered from chickens inoculated with HVT highly passaged in vitro, which had become a high producer of cell-free virus in vitro, and grew equally well at 37 C and 41 C.", "contents": "Marek's disease virus and herpesvirus of turkey noninfective to chickens, obtained by repeated in vitro passages. The relation between the passage level of Marek's disease virus, C2 strain, and of herpesvirus of turkey (HVT), O1 strain, in cell culture and the level of the serological response of chickens to these viruses was examined. In both cases the immune response of chickens to these viruses decreased with increase in the number of in vitro passages of virus. Virus was not recovered from chickens inoculated with HVT highly passaged in vitro, which had become a high producer of cell-free virus in vitro, and grew equally well at 37 C and 41 C."}
{"id": "PMID:231438", "title": "Studies on the polypeptides of varicella-zoster (V-Z) virus. 1. Detection of varicella-zoster virus polypeptides in infected cells.", "content": "Virus-induced polypeptides in cells infected with varicella-zoster virus (VZV) were analyzed by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and autoradiography. When human embryonic lung (HEL) cells infected with the Oka strain of VZV were labelled with 35S-methionine or 14C-glucosamine from 40 hr to 46 hr after infection, at least 18 VZV-induced polypeptides and 10 glycoproteins could  be identified in the infected cells. The molecular weights of the polypeptides and glycoproteins ranged from about 145,000 to 23,000, and from about 105,000 to 48,000, respectively. Lysates of VZV-infected cells were treated with specific antisera prepared in green monkeys or guinea-pigs, and analysed by SDS-PAGE and fluorography. In all, 33 polypeptides (with molecular weight of about 145,000 to 22,000) and 13 glycoproteins (molecular weight, about 105,000 to 38,000) were found in the immunoprecipitates. None of these polypeptides and glycoproteins were detected when infected cells cultured in the presence of phosphonoacetic acid (PAA) were treated in the same way.", "contents": "Studies on the polypeptides of varicella-zoster (V-Z) virus. 1. Detection of varicella-zoster virus polypeptides in infected cells. Virus-induced polypeptides in cells infected with varicella-zoster virus (VZV) were analyzed by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and autoradiography. When human embryonic lung (HEL) cells infected with the Oka strain of VZV were labelled with 35S-methionine or 14C-glucosamine from 40 hr to 46 hr after infection, at least 18 VZV-induced polypeptides and 10 glycoproteins could  be identified in the infected cells. The molecular weights of the polypeptides and glycoproteins ranged from about 145,000 to 23,000, and from about 105,000 to 48,000, respectively. Lysates of VZV-infected cells were treated with specific antisera prepared in green monkeys or guinea-pigs, and analysed by SDS-PAGE and fluorography. In all, 33 polypeptides (with molecular weight of about 145,000 to 22,000) and 13 glycoproteins (molecular weight, about 105,000 to 38,000) were found in the immunoprecipitates. None of these polypeptides and glycoproteins were detected when infected cells cultured in the presence of phosphonoacetic acid (PAA) were treated in the same way."}
{"id": "PMID:231439", "title": "The presence of herpes simplex virus DNA in hamster embryo cells transformed by a temperature sensitive mutant, TS-4.", "content": "Hamster embryo cells transformed with a temperature sensitive mutant of HSV-2, ts-4T, were examined for the presence of viral genomes. DNA-DNA reassociation kinetics showed that only a small portion (11 +/- 4%) of HSV-2 was present in the transformed cells.", "contents": "The presence of herpes simplex virus DNA in hamster embryo cells transformed by a temperature sensitive mutant, TS-4. Hamster embryo cells transformed with a temperature sensitive mutant of HSV-2, ts-4T, were examined for the presence of viral genomes. DNA-DNA reassociation kinetics showed that only a small portion (11 +/- 4%) of HSV-2 was present in the transformed cells."}
{"id": "PMID:231454", "title": "Kinetics of 5--nucleotidase in sera of liver cirrhotic and normal Iraqi individuals.", "content": "5'-Nucleotidase activity was elevated in patients with liver cirrhosis; greater values of 5'-Nucleotidase activity were found in biliary cirrhosis, 5'-Nucleotidase from liver cirrhotic sera was less stable than from normal sera. The velocity of 5'Nucleotidase from liver cirrhotic sera per minute, at t = 10, was greater than normal controls. The optimum (S) for 5'-Nucleotidase was found to be 1.0 mM A-5'-MP, for both normal and liver cirrhotic sera. Km (A-5'-MP) and (2'-d-A-5'-MP) of 5'-Nucleotidase was found to be significantly lower in patients with liver cirrhosis than normal controls.", "contents": "Kinetics of 5--nucleotidase in sera of liver cirrhotic and normal Iraqi individuals. 5'-Nucleotidase activity was elevated in patients with liver cirrhosis; greater values of 5'-Nucleotidase activity were found in biliary cirrhosis, 5'-Nucleotidase from liver cirrhotic sera was less stable than from normal sera. The velocity of 5'Nucleotidase from liver cirrhotic sera per minute, at t = 10, was greater than normal controls. The optimum (S) for 5'-Nucleotidase was found to be 1.0 mM A-5'-MP, for both normal and liver cirrhotic sera. Km (A-5'-MP) and (2'-d-A-5'-MP) of 5'-Nucleotidase was found to be significantly lower in patients with liver cirrhosis than normal controls."}
{"id": "PMID:231455", "title": "Calcium-induced fusion of proteoliposomes and protein-free liposomes. Effect of their phosphatidylethanolamine content on the structure of fused vesicles.", "content": "The acidic phospholipid cardiolipin was shown to be very efficient in promoting calcium-induced fusion of proteoliposomes. The degree of fusion was dependent on the phosphatidylethanolamine content of the vesicles. Addition of CaCl2 to proteoliposomes containing phosphatidylcholine and cardiolipin but without phosphatidylethanolamine did not induce fusion. Fusion of cytochrome oxidase vesicles, containing less than 50 mol% phosphatidylethanolamine resulted in monolamellar vesicles with a diameter of about 200 nm. The vesicles could be induced to fuse further by establishing an osmotic pressure across their membranes. When proteoliposomes containing more than 50 mol% phosphatidylethanolamine were fused, large vesicles with a diameter exceeding 1 micrometer were formed. They appeared in the electron microscope as a mixture of multilamellar and monolamellar vesicles. Fusion of corresponding liposomes resulted in formation of even larger structures appearing as dense multilamellar bodies and paracrystalline honeycomb-like lattices.", "contents": "Calcium-induced fusion of proteoliposomes and protein-free liposomes. Effect of their phosphatidylethanolamine content on the structure of fused vesicles. The acidic phospholipid cardiolipin was shown to be very efficient in promoting calcium-induced fusion of proteoliposomes. The degree of fusion was dependent on the phosphatidylethanolamine content of the vesicles. Addition of CaCl2 to proteoliposomes containing phosphatidylcholine and cardiolipin but without phosphatidylethanolamine did not induce fusion. Fusion of cytochrome oxidase vesicles, containing less than 50 mol% phosphatidylethanolamine resulted in monolamellar vesicles with a diameter of about 200 nm. The vesicles could be induced to fuse further by establishing an osmotic pressure across their membranes. When proteoliposomes containing more than 50 mol% phosphatidylethanolamine were fused, large vesicles with a diameter exceeding 1 micrometer were formed. They appeared in the electron microscope as a mixture of multilamellar and monolamellar vesicles. Fusion of corresponding liposomes resulted in formation of even larger structures appearing as dense multilamellar bodies and paracrystalline honeycomb-like lattices."}
{"id": "PMID:231456", "title": "Subcellular targets of the soluble SiO2-liberated macrophage factors in experimental granulation tissue.", "content": "The supernatant from SiO2-treated macrophages increased the incorporated radioactivity of collagen in the incubated experimental granulation tissue slices, especially in the rough endoplasmic reticulum fraction, markedly over that in the respective control preparation. The effect was observed after a 20 min incubation and increases linearly at least up to 3 h. The amount of RNA and phospholipids in the rough endoplasmic reticulum, calculated per protein, increased simultaneously in the incubated slices. The incorporation of the radioactive precursors into DNA in the slices and in the nuclei from proliferating granulation tissue was enhanced significantly by the soluble fraction from SiO2-treated macrophages. This effect could be seen after a 40 min incubation in the slices and after 5 min in the nuclei, when the incorporated radioactivity in DNA began to decrease in the control experiments.", "contents": "Subcellular targets of the soluble SiO2-liberated macrophage factors in experimental granulation tissue. The supernatant from SiO2-treated macrophages increased the incorporated radioactivity of collagen in the incubated experimental granulation tissue slices, especially in the rough endoplasmic reticulum fraction, markedly over that in the respective control preparation. The effect was observed after a 20 min incubation and increases linearly at least up to 3 h. The amount of RNA and phospholipids in the rough endoplasmic reticulum, calculated per protein, increased simultaneously in the incubated slices. The incorporation of the radioactive precursors into DNA in the slices and in the nuclei from proliferating granulation tissue was enhanced significantly by the soluble fraction from SiO2-treated macrophages. This effect could be seen after a 40 min incubation in the slices and after 5 min in the nuclei, when the incorporated radioactivity in DNA began to decrease in the control experiments."}
{"id": "PMID:231457", "title": "Cyanide reactivity of cytochrome c derivatives.", "content": "The kinetic rates and equilibrium association constants for cyanide binding have been measured for a series of cytochrome c derivatives as a probe of heme accessibility. The series included horse and yeast cytochromes iodinated at Tyr 67 and 74, horse cytochrome formylated at Trp 59 in both a low and high redox potential form, the Met 80 sulfoxide derivative of horse cytochrome and the N-acylisourea heme propionate derivative of tuna cytochrome. Native cytochromes c are well known to bind cyanide slowly in a reaction simply first order both in cytochrome and cyanide up to at least 100 mM in cyanide. The derivative demonstrate markedly different kinetics which indicate the following conclusions. (1) In spite of chemical modification at different loci, all the derivatives have highly similar reactivity, suggesting common ligation structures and mechanisms for reaction. (2) Compared to native cytochromes, reaction rates are 10-20 fold greater. This is in accord with a more accessible heme crevice, but not a completely opened crevice. For the completely opened case, rate increases are expected to be between three and five orders of magnitude. (3) Reaction rates are either independent of cyanide concentration (zero order) or show only slight variation. A mechanism which accounts for the data over four orders of magnitude in concentration postulates a protein conformation step, opening of the heme crevice, as the rate determining step. This conformation change has a limiting rate of 6 . 10(-2) s-1.", "contents": "Cyanide reactivity of cytochrome c derivatives. The kinetic rates and equilibrium association constants for cyanide binding have been measured for a series of cytochrome c derivatives as a probe of heme accessibility. The series included horse and yeast cytochromes iodinated at Tyr 67 and 74, horse cytochrome formylated at Trp 59 in both a low and high redox potential form, the Met 80 sulfoxide derivative of horse cytochrome and the N-acylisourea heme propionate derivative of tuna cytochrome. Native cytochromes c are well known to bind cyanide slowly in a reaction simply first order both in cytochrome and cyanide up to at least 100 mM in cyanide. The derivative demonstrate markedly different kinetics which indicate the following conclusions. (1) In spite of chemical modification at different loci, all the derivatives have highly similar reactivity, suggesting common ligation structures and mechanisms for reaction. (2) Compared to native cytochromes, reaction rates are 10-20 fold greater. This is in accord with a more accessible heme crevice, but not a completely opened crevice. For the completely opened case, rate increases are expected to be between three and five orders of magnitude. (3) Reaction rates are either independent of cyanide concentration (zero order) or show only slight variation. A mechanism which accounts for the data over four orders of magnitude in concentration postulates a protein conformation step, opening of the heme crevice, as the rate determining step. This conformation change has a limiting rate of 6 . 10(-2) s-1."}
{"id": "PMID:231458", "title": "The redox properties and heme environment of cytochrome c-551.5 from Desulfuromonas acetoxidans.", "content": "The environment of the three heme groups in cytochrome c-551.5 from Desulfuromonas acetoxidans was investigated by the technique of solvent perturbation difference spectroscopy. The hemeoctapeptide from cytochrome c plus added imidazole was used as a model compound for the fully exposed chromophore. The average heme exposure in both the ferric and ferrous cytochromes c-551.5 was found to be considerably greater than that previously observed for the monoheme mitochondrial cytochrome c and Prosthecochloris cytochrome c-555. Differences in the average heme exposure for ferric and ferrous cytochromes c-551.5 suggested that a change in oxidation state is accompanied by a change in conformation. A spectrophotometric redox titration of the protein yielded a sigmoidal plot of the potential versus the logarithm of the ratio of oxidized to reduced heme. The resolved plot indicated that two hemes were characterized by a E'o of -177 mV and the third E'o of -102 mV. Each of the resolved steps had an n value of 1 indicating that cytochrome c-551.5 transfers electrons singly.", "contents": "The redox properties and heme environment of cytochrome c-551.5 from Desulfuromonas acetoxidans. The environment of the three heme groups in cytochrome c-551.5 from Desulfuromonas acetoxidans was investigated by the technique of solvent perturbation difference spectroscopy. The hemeoctapeptide from cytochrome c plus added imidazole was used as a model compound for the fully exposed chromophore. The average heme exposure in both the ferric and ferrous cytochromes c-551.5 was found to be considerably greater than that previously observed for the monoheme mitochondrial cytochrome c and Prosthecochloris cytochrome c-555. Differences in the average heme exposure for ferric and ferrous cytochromes c-551.5 suggested that a change in oxidation state is accompanied by a change in conformation. A spectrophotometric redox titration of the protein yielded a sigmoidal plot of the potential versus the logarithm of the ratio of oxidized to reduced heme. The resolved plot indicated that two hemes were characterized by a E'o of -177 mV and the third E'o of -102 mV. Each of the resolved steps had an n value of 1 indicating that cytochrome c-551.5 transfers electrons singly."}
{"id": "PMID:231459", "title": "Modification of human serum albumin with N-(2,5-dinitro-4-fluorophenyl)-4-amino-2,2,6,6-tetramethyl-piperidinooxy radical.", "content": "Human serum albumin has been treated with the spin-labeling reagent indicated in the title. Ultraviolet spectral studies of the protein so modified suggest that reaction takes place at lysine and tyrosine sidechains; kinetic experiments indicate that there are two especially reactive amino groups of the protein which are preferentially modified. Evidence is presented that these groups include the one acetylated by aspirin (Lys-199) or those arylated by 2.6-dinitro-4-trifluoromethylbenzenesulfonate. Esr experiments show that bound spin labels have about the same correlation time expected for overall tumbling of the protein; ESR observations indicate that molecular freedom near the spin labels is not increased when the protein is transferred to 8 M urea.", "contents": "Modification of human serum albumin with N-(2,5-dinitro-4-fluorophenyl)-4-amino-2,2,6,6-tetramethyl-piperidinooxy radical. Human serum albumin has been treated with the spin-labeling reagent indicated in the title. Ultraviolet spectral studies of the protein so modified suggest that reaction takes place at lysine and tyrosine sidechains; kinetic experiments indicate that there are two especially reactive amino groups of the protein which are preferentially modified. Evidence is presented that these groups include the one acetylated by aspirin (Lys-199) or those arylated by 2.6-dinitro-4-trifluoromethylbenzenesulfonate. Esr experiments show that bound spin labels have about the same correlation time expected for overall tumbling of the protein; ESR observations indicate that molecular freedom near the spin labels is not increased when the protein is transferred to 8 M urea."}
{"id": "PMID:231460", "title": "[Monkey liver microsomal glucose-6-phosphatase].", "content": "Kinetic studies indicate that glucose-6-phosphatase is a multifunctional enzyme. a) Phosphohydrolase activities. The mannose-6-phosphatase activity is low (Km = 8 mM, VM = 90 nmoles. min-1mg-1). The enzyme shows a strong affinity for glucose-6-phosphate (Km = 2.5 mM, VM = 220 nmoles.min-1mg-1). beta-glycerophosphate (K1 = 30 mM), D-glucose (Ki = 120 mM) are mixed type inhibitors; pyrophosphate (Ki = 2 mM) is a non competitive one. b) Phosphotransferase activities. Di and triphosphate adenylic nucleosides or phosphoenol pyruvate are not substrates. Carbamylphosphate serves as a phosphoryl donor with D-glucose as acceptor. The phosphate transfer is consisstent with a random mechanism in which the binding of one substrate increases the enzymes affinity for the second substrate. Apparent Km values for carbamyl-phosphate range from 5.2 mM (D-glucose concentration leads to infinity) to 8 mM (D-glucose concentration leads to 0). The corresponding apparent Km values for D-glucose are 59 mM (carbamyl-phosphate concentration leads to infinity) to 119 mM (carbamyl-phosphate concentration leads to 0). Maximal reaction velocity with infinite levels of both substrates is 270 nmoles.min-1.mg-1. Pyrophosphate is a poor phosphoryl donnor (Km = 55 mM with D-glucose concentration 250 mM). In addition we do not find any latency; detergents, namely sodium deoxycholate, Triton X 100 do not affect or inhibit glucose-6-phosphatase activity.", "contents": "[Monkey liver microsomal glucose-6-phosphatase]. Kinetic studies indicate that glucose-6-phosphatase is a multifunctional enzyme. a) Phosphohydrolase activities. The mannose-6-phosphatase activity is low (Km = 8 mM, VM = 90 nmoles. min-1mg-1). The enzyme shows a strong affinity for glucose-6-phosphate (Km = 2.5 mM, VM = 220 nmoles.min-1mg-1). beta-glycerophosphate (K1 = 30 mM), D-glucose (Ki = 120 mM) are mixed type inhibitors; pyrophosphate (Ki = 2 mM) is a non competitive one. b) Phosphotransferase activities. Di and triphosphate adenylic nucleosides or phosphoenol pyruvate are not substrates. Carbamylphosphate serves as a phosphoryl donor with D-glucose as acceptor. The phosphate transfer is consisstent with a random mechanism in which the binding of one substrate increases the enzymes affinity for the second substrate. Apparent Km values for carbamyl-phosphate range from 5.2 mM (D-glucose concentration leads to infinity) to 8 mM (D-glucose concentration leads to 0). The corresponding apparent Km values for D-glucose are 59 mM (carbamyl-phosphate concentration leads to infinity) to 119 mM (carbamyl-phosphate concentration leads to 0). Maximal reaction velocity with infinite levels of both substrates is 270 nmoles.min-1.mg-1. Pyrophosphate is a poor phosphoryl donnor (Km = 55 mM with D-glucose concentration 250 mM). In addition we do not find any latency; detergents, namely sodium deoxycholate, Triton X 100 do not affect or inhibit glucose-6-phosphatase activity."}
{"id": "PMID:231461", "title": "Isolation and identification of mutants constitutive for aspartokinase III synthesis in Escherichia coli K 12.", "content": "We devised a procedure in order to isolate, in Escherichia coli, constitutive mutants for aspartokinase III synthesis, the first enzyme of the lysine regulon. It consists of the introduction of a limiting step in lysine biosynthesis, by the use of the partial suppression of a nonsense mutation. For the first time we could isolate many constitutive mutants. Their characteristics (cotransduction with the lysC structural gene; no effect on the synthesis of other enzymes of the regulon; cis-dominance) lead to classify these mutations as operator-type. The fact that no repressor mutations could be isolated is discussed.", "contents": "Isolation and identification of mutants constitutive for aspartokinase III synthesis in Escherichia coli K 12. We devised a procedure in order to isolate, in Escherichia coli, constitutive mutants for aspartokinase III synthesis, the first enzyme of the lysine regulon. It consists of the introduction of a limiting step in lysine biosynthesis, by the use of the partial suppression of a nonsense mutation. For the first time we could isolate many constitutive mutants. Their characteristics (cotransduction with the lysC structural gene; no effect on the synthesis of other enzymes of the regulon; cis-dominance) lead to classify these mutations as operator-type. The fact that no repressor mutations could be isolated is discussed."}
{"id": "PMID:231463", "title": "[Study of the enzymatic hydrolysis of a phosphonic ester using microcalorimetry].", "content": "A \"Batch\" microcalorimeter is used at 30 degrees C for the study of the hydrolysis of 4-nitro-phenylphenylphosphonate with a calf-intestinal phosphonate esterase, in a tris buffer, pH 8. The yield of enzymatic hydrolysis is estimated by spectrophotometric determination of the p--nitrophenol evolved; we have then calculated the apparent molar enthalph of the reaction. (delta Happ = -72,2 kj. mol-1). Phenylphosphonic acid, the second reaction product, is not transphosphonylated on tris. The second acidity of phenylphosphonic acid was studied at 30 degrees C by sodium hydroxide electrotitration (pKa2 = 7,13) and by \"Flow\" microcalorimetry (delta Hionization = 19,8 kj.mol-1). In the same manner at 30 degrees C, we measured the heat of ionization of p-nitrophenol (delta Hionization = 26,75 kj.mol-1). These findings allow a calculation for the actual heat of hydrolysis of 4-nitro-phenyl-phenylphosphonate (delta Hrho = -29,7 kj.mol-1).", "contents": "[Study of the enzymatic hydrolysis of a phosphonic ester using microcalorimetry]. A \"Batch\" microcalorimeter is used at 30 degrees C for the study of the hydrolysis of 4-nitro-phenylphenylphosphonate with a calf-intestinal phosphonate esterase, in a tris buffer, pH 8. The yield of enzymatic hydrolysis is estimated by spectrophotometric determination of the p--nitrophenol evolved; we have then calculated the apparent molar enthalph of the reaction. (delta Happ = -72,2 kj. mol-1). Phenylphosphonic acid, the second reaction product, is not transphosphonylated on tris. The second acidity of phenylphosphonic acid was studied at 30 degrees C by sodium hydroxide electrotitration (pKa2 = 7,13) and by \"Flow\" microcalorimetry (delta Hionization = 19,8 kj.mol-1). In the same manner at 30 degrees C, we measured the heat of ionization of p-nitrophenol (delta Hionization = 26,75 kj.mol-1). These findings allow a calculation for the actual heat of hydrolysis of 4-nitro-phenyl-phenylphosphonate (delta Hrho = -29,7 kj.mol-1)."}
{"id": "PMID:231464", "title": "Biological and immunological aspects of small cell carcinoma of the lung in relation to ectopic hormone production.", "content": "Small cell carcinoma share morphological and functional characteristics with normal Kulchitsky cells (K-cells) of the bronchial tree. This tumor is thought to reflect a neoplastic transformation of the pulmonary APUD cells because of the morphological similarities with K-cells, the association with paraneoplastic syndromes and the high incidence of ectopic hormone production. The peptide hormones produced and secreted by small cell carcinoma can be used as tumor markers to guide diagnosis and to monitor chemotherapy. They may be of particular value in following the course of a patient and in detecting early recurrences. Some of the hormonal substances produced by the tumor have the biochemical characteristics of prohormones. The difference between the abnormal hormones and their physiological counterparts probably will lead to the development of more specific marker assays. On the other hand, some of the atypical hormones have autoantigenic properties, as they occur in circulating immune complexes of patients with small cell carcinoma. The correlation between ectopic hormone production and host immunity might be of importance for the development of future treatment modalities.", "contents": "Biological and immunological aspects of small cell carcinoma of the lung in relation to ectopic hormone production. Small cell carcinoma share morphological and functional characteristics with normal Kulchitsky cells (K-cells) of the bronchial tree. This tumor is thought to reflect a neoplastic transformation of the pulmonary APUD cells because of the morphological similarities with K-cells, the association with paraneoplastic syndromes and the high incidence of ectopic hormone production. The peptide hormones produced and secreted by small cell carcinoma can be used as tumor markers to guide diagnosis and to monitor chemotherapy. They may be of particular value in following the course of a patient and in detecting early recurrences. Some of the hormonal substances produced by the tumor have the biochemical characteristics of prohormones. The difference between the abnormal hormones and their physiological counterparts probably will lead to the development of more specific marker assays. On the other hand, some of the atypical hormones have autoantigenic properties, as they occur in circulating immune complexes of patients with small cell carcinoma. The correlation between ectopic hormone production and host immunity might be of importance for the development of future treatment modalities."}
{"id": "PMID:231465", "title": "Corticosteroid-dependent alterations of human myelopoiesis in vitro.", "content": "We have demonstrated in this study that corticosteroids modify cellular interactions enhancing CSA production. This phenomenon may contribute to the leukocytosis-promoting action of these hormones, although at present it is unknown whether this mechanism is more important in vivo than steroid-dependent changes in the circulation and redistribution of phagocytic cells. The observation that corticosteroids impair phagocyte functions is difficult to reconcile with the well known fact that hypercorticism as a part of the normal body defense to stress (6). In view of our data it appears, however, that these possible detrimental effects of corticosteroids on mature white blood cells are counteracted by their stimulatory action on the production of new phagocytic cells. Such a conclusion is in accord with Joyce and Charvenick (20) who showed that those hormones enhance the return of GM-CFU in cyclophosphamide-treated mice and improve tolerance to infection.", "contents": "Corticosteroid-dependent alterations of human myelopoiesis in vitro. We have demonstrated in this study that corticosteroids modify cellular interactions enhancing CSA production. This phenomenon may contribute to the leukocytosis-promoting action of these hormones, although at present it is unknown whether this mechanism is more important in vivo than steroid-dependent changes in the circulation and redistribution of phagocytic cells. The observation that corticosteroids impair phagocyte functions is difficult to reconcile with the well known fact that hypercorticism as a part of the normal body defense to stress (6). In view of our data it appears, however, that these possible detrimental effects of corticosteroids on mature white blood cells are counteracted by their stimulatory action on the production of new phagocytic cells. Such a conclusion is in accord with Joyce and Charvenick (20) who showed that those hormones enhance the return of GM-CFU in cyclophosphamide-treated mice and improve tolerance to infection."}
{"id": "PMID:231466", "title": "Cutaneous cholesterol and plasma lipoproteins in young subjects.", "content": "The present report concerns the biochemical and anatomo-pathological study of the skin and the plasma lipoprotein fractions in a young population (average age : 22 +/- 1.5 years). The levels of cutaneous cholesterol and the ratio HDL cholesterol/total cholesterol are closely linked even through the histological structure of the skin is still normal; the level of cutaneous cholesterol giving a good indication of the degree of vascular ageing. The observations confirm the usefulness of measuring these two parameters in the detection of early atherosclerosis.", "contents": "Cutaneous cholesterol and plasma lipoproteins in young subjects. The present report concerns the biochemical and anatomo-pathological study of the skin and the plasma lipoprotein fractions in a young population (average age : 22 +/- 1.5 years). The levels of cutaneous cholesterol and the ratio HDL cholesterol/total cholesterol are closely linked even through the histological structure of the skin is still normal; the level of cutaneous cholesterol giving a good indication of the degree of vascular ageing. The observations confirm the usefulness of measuring these two parameters in the detection of early atherosclerosis."}
{"id": "PMID:231468", "title": "[Chronic polyarthritis: role of polymorphonuclear leukocytes in the destruction of pannus-free articular cartilage].", "content": "The synovial fluid (SF) of RA patients contains large amounts of PMN which are well equipped with neutral enzymes to degrade articular cartilage: elastase and cathepsin G, which both destroy proteoglycans and native collagen, as well as 2 types of collagenoases. Indirect evidence suggests that PMN might be important in the destruction of RA articular cartilage. In 19 SF of RA patients no free elastase or collagenase was found. Using immune histochemical methods, we observed that PMN and macrophages of SF contain both elastase and alpha 1-anti-trypsin and alpha 2-macroglobulin. Peripheral PMN - but not monocytes - contain elastase, however both types of cells lack alpha 1-antitrypsin and alpha 2-macroglobulin. Elastase is demonstratable in the superficial layer of pannus free RA articular cartilage. These findings suggest that neutral proteinases from PMN in RA SF are generally neutralized by physiologic inhibitors and removed by phagocytes. The enzyme-inhibitor interaction might be bypassed during \"frustrated phagocytosis\" so that enzymes like PMN elastase can damage RA articular cartilage.", "contents": "[Chronic polyarthritis: role of polymorphonuclear leukocytes in the destruction of pannus-free articular cartilage]. The synovial fluid (SF) of RA patients contains large amounts of PMN which are well equipped with neutral enzymes to degrade articular cartilage: elastase and cathepsin G, which both destroy proteoglycans and native collagen, as well as 2 types of collagenoases. Indirect evidence suggests that PMN might be important in the destruction of RA articular cartilage. In 19 SF of RA patients no free elastase or collagenase was found. Using immune histochemical methods, we observed that PMN and macrophages of SF contain both elastase and alpha 1-anti-trypsin and alpha 2-macroglobulin. Peripheral PMN - but not monocytes - contain elastase, however both types of cells lack alpha 1-antitrypsin and alpha 2-macroglobulin. Elastase is demonstratable in the superficial layer of pannus free RA articular cartilage. These findings suggest that neutral proteinases from PMN in RA SF are generally neutralized by physiologic inhibitors and removed by phagocytes. The enzyme-inhibitor interaction might be bypassed during \"frustrated phagocytosis\" so that enzymes like PMN elastase can damage RA articular cartilage."}
{"id": "PMID:231469", "title": "Collagenase and prostaglandin in connective tissue destruction: cell-cell and humoral interactions.", "content": "Connective tissue destruction is a major characteristic of chornic rheumatoid arthritis (RA). This process is accompanied by local cellular and humoral inflammatory reactions. Long-term cultures of adherent synovial cells (ASC) from patients with RA produce large amounts of collagenase and prostaglandin (PGE2), two substances that play a role in the degradation of joint structures. Lvels of collagenase and PGE2 can be stimulated (up to several hundred-fold) with a soluble factor (MCF) from cultured peripheral blood mononuclear cells (MW approximately 14,000). The monocyte-macrophages alone produce MCF but can be stimulated directly with Fc fragments of immunoglobulin or concanavalin A to increase MCF production. Addition of T lymphocytes in the presence of lectin or antigen significantly enhances the production of MCF. MCF affects other biological processes in synovial cells such as the rate of collagen synthesis, cell proliferation and sensitivity to PGE2 as well as collagen itself can further modulate collagenase release by the synovial cells and function in an amplificative loop. The understanding of these interactions between cells, mediator-effector substances and connective tissue substrates may provide a basis for devising more rational approaches to therapy of the destructive lesions which characterize RA.", "contents": "Collagenase and prostaglandin in connective tissue destruction: cell-cell and humoral interactions. Connective tissue destruction is a major characteristic of chornic rheumatoid arthritis (RA). This process is accompanied by local cellular and humoral inflammatory reactions. Long-term cultures of adherent synovial cells (ASC) from patients with RA produce large amounts of collagenase and prostaglandin (PGE2), two substances that play a role in the degradation of joint structures. Lvels of collagenase and PGE2 can be stimulated (up to several hundred-fold) with a soluble factor (MCF) from cultured peripheral blood mononuclear cells (MW approximately 14,000). The monocyte-macrophages alone produce MCF but can be stimulated directly with Fc fragments of immunoglobulin or concanavalin A to increase MCF production. Addition of T lymphocytes in the presence of lectin or antigen significantly enhances the production of MCF. MCF affects other biological processes in synovial cells such as the rate of collagen synthesis, cell proliferation and sensitivity to PGE2 as well as collagen itself can further modulate collagenase release by the synovial cells and function in an amplificative loop. The understanding of these interactions between cells, mediator-effector substances and connective tissue substrates may provide a basis for devising more rational approaches to therapy of the destructive lesions which characterize RA."}
{"id": "PMID:231470", "title": "[Arthropathies due to calcium pyrophosphates].", "content": "Articular chondrocalcinosis results from the deposits of calcium pyrophosphate microcrystals in the articular hyalin and fibrocartilages, the synovium and at times the tendons. In our area it is seen most frequently as isolated cases in the elderly and may be asymptomatic. When the affected joints present clinical manifestations, they vary from acute to subacute or chronic recurrent arthritis. A marked articular destruction can be observed in some cases. There is a classical radiological picture: linear opacities are most frequently seen localized in the mid-zone layer of the hyalin cartilage running parallel to but at a certain distance from the bone cortex. A part of our research has shown that in contrast to urate gout, articular chondrocalcinosis results from a metabolic disturbance of the calcium pyrophosphate localized almost exclusively in the same articular structures. Precise information is lacking at the present time to explain why calcium pyrophosphate mycrocrystals accumulate in the cartilage, the synovium and at times at the tendons; nor do we understand the precise role played by the pyrophosphate in bone and cartilage destruction.", "contents": "[Arthropathies due to calcium pyrophosphates]. Articular chondrocalcinosis results from the deposits of calcium pyrophosphate microcrystals in the articular hyalin and fibrocartilages, the synovium and at times the tendons. In our area it is seen most frequently as isolated cases in the elderly and may be asymptomatic. When the affected joints present clinical manifestations, they vary from acute to subacute or chronic recurrent arthritis. A marked articular destruction can be observed in some cases. There is a classical radiological picture: linear opacities are most frequently seen localized in the mid-zone layer of the hyalin cartilage running parallel to but at a certain distance from the bone cortex. A part of our research has shown that in contrast to urate gout, articular chondrocalcinosis results from a metabolic disturbance of the calcium pyrophosphate localized almost exclusively in the same articular structures. Precise information is lacking at the present time to explain why calcium pyrophosphate mycrocrystals accumulate in the cartilage, the synovium and at times at the tendons; nor do we understand the precise role played by the pyrophosphate in bone and cartilage destruction."}
{"id": "PMID:231475", "title": "Hierarchical and parallel mechanisms in the organization of visual cortex.", "content": "We argue that it seems fruitful to regard the retino-geniculate-cortical pathway, and perhaps the visual pathways in general, as comprising distinct neuronal channels which begin with the major groupings of ganglion cells, and subserve distinct functions within the overall operation of the visual system. One problem for future work is to determine the extent and, equally importantly, the limitations of the idea of independently functioning neuronal channels operating within the visual system. Some evidence of those limitations is already available. Kulikowski and Tolhurst have provided evidence suggesting that pattern detection is mediated by the X-like system at high spatial frequencies and by the Y-like system at low frequencies, but that at intermediate frequencies, both systems are likely to contribute to this function. Again, there is already physiological and psychophysical evidence of inhibitory interaction between X- and Y-cell systems, which may contribute to their functioning. That is, although there is little evidence of excitatory interaction between W-, X- and Y-cell systems, at least up to the first cortical synapse, the functioning of, say, the X-cell system may depend on the inhibitory influences impinging on it from Y-cell activity. Further, it may prove to be the case that one cell 'system' may be involved in several distinct functions and considerable work may be required to establish whether or not these functions can be considered constituent parts of an overall function, such as 'ambient' or 'foveal' vision. In the following section we suggest a classification and terminology for visual neurones which may provide a framework for future work on these lines.", "contents": "Hierarchical and parallel mechanisms in the organization of visual cortex. We argue that it seems fruitful to regard the retino-geniculate-cortical pathway, and perhaps the visual pathways in general, as comprising distinct neuronal channels which begin with the major groupings of ganglion cells, and subserve distinct functions within the overall operation of the visual system. One problem for future work is to determine the extent and, equally importantly, the limitations of the idea of independently functioning neuronal channels operating within the visual system. Some evidence of those limitations is already available. Kulikowski and Tolhurst have provided evidence suggesting that pattern detection is mediated by the X-like system at high spatial frequencies and by the Y-like system at low frequencies, but that at intermediate frequencies, both systems are likely to contribute to this function. Again, there is already physiological and psychophysical evidence of inhibitory interaction between X- and Y-cell systems, which may contribute to their functioning. That is, although there is little evidence of excitatory interaction between W-, X- and Y-cell systems, at least up to the first cortical synapse, the functioning of, say, the X-cell system may depend on the inhibitory influences impinging on it from Y-cell activity. Further, it may prove to be the case that one cell 'system' may be involved in several distinct functions and considerable work may be required to establish whether or not these functions can be considered constituent parts of an overall function, such as 'ambient' or 'foveal' vision. In the following section we suggest a classification and terminology for visual neurones which may provide a framework for future work on these lines."}
{"id": "PMID:231476", "title": "[Immunohistochemical study of the adenohypophysis of the monkey Macaca irus with the use of antibodies anti 1-24-ACTH, anti 17-39-ACTH, anti alpha-and beta-endorphins, anti beta-LPM].", "content": "Indirect immunofluorescence technique with anti1-24- and anti17-39 ACTH, anti alpha- and anti beta-endorphins, anti beta-LPH sera has allowed us to detect a cellular type in the anterior lobe of the hypophysis of Macacus irus which react simultaneously with these five antisera. These cells are especially localized in the ventro-medial zone, but there are also present in the pars distalis, under the glandular capsule, and in the lateral lobes, amid the other cellular types. The cells of the intermediate lobe react on the whole with anti1-24-, these antisera are also immunoreactive with the anti alpha- and anti17-39ACTH and anti beta-LPH ; SOME CELLS, WHich react with anti beta-endorphin antisera. The adenohypophysis of Macacus irus contains therefore two categories of cells reacting with the above mentioned antisera : one of this type, localized in the anterior lobe and in the intermediate lobe, react simultaneously with the five antisera, the other type, localized only in the intermediate lobe does not react with the antiendorphins antisera.", "contents": "[Immunohistochemical study of the adenohypophysis of the monkey Macaca irus with the use of antibodies anti 1-24-ACTH, anti 17-39-ACTH, anti alpha-and beta-endorphins, anti beta-LPM]. Indirect immunofluorescence technique with anti1-24- and anti17-39 ACTH, anti alpha- and anti beta-endorphins, anti beta-LPH sera has allowed us to detect a cellular type in the anterior lobe of the hypophysis of Macacus irus which react simultaneously with these five antisera. These cells are especially localized in the ventro-medial zone, but there are also present in the pars distalis, under the glandular capsule, and in the lateral lobes, amid the other cellular types. The cells of the intermediate lobe react on the whole with anti1-24-, these antisera are also immunoreactive with the anti alpha- and anti17-39ACTH and anti beta-LPH ; SOME CELLS, WHich react with anti beta-endorphin antisera. The adenohypophysis of Macacus irus contains therefore two categories of cells reacting with the above mentioned antisera : one of this type, localized in the anterior lobe and in the intermediate lobe, react simultaneously with the five antisera, the other type, localized only in the intermediate lobe does not react with the antiendorphins antisera."}
{"id": "PMID:231477", "title": "[Presence of UTP:D-GLUCOSE-1-phosphate uridylyltransferase in liver microsomes of the eel (Conger vulgaris)].", "content": "An activity UTP : D-glucose-1-phosphate uridylyltransferase is located in the microsomal membranes of conger liver. The properties of this enzyme are studied and compared to the soluble activity. The microsomal activity is partially liberated from the membrane by freezing and thawing and by the means of a neutral detergent, Triton X-100. The enzyme is latent in the membranes and totally inhibited by phospholipase A2. This microsomal enzyme could be the last of a membranous biosynthetic pathway for UDP-glucose, as conger liver microsomes contain also a membranous glucokinase and a membranous phosphoglucomutase.", "contents": "[Presence of UTP:D-GLUCOSE-1-phosphate uridylyltransferase in liver microsomes of the eel (Conger vulgaris)]. An activity UTP : D-glucose-1-phosphate uridylyltransferase is located in the microsomal membranes of conger liver. The properties of this enzyme are studied and compared to the soluble activity. The microsomal activity is partially liberated from the membrane by freezing and thawing and by the means of a neutral detergent, Triton X-100. The enzyme is latent in the membranes and totally inhibited by phospholipase A2. This microsomal enzyme could be the last of a membranous biosynthetic pathway for UDP-glucose, as conger liver microsomes contain also a membranous glucokinase and a membranous phosphoglucomutase."}
{"id": "PMID:231478", "title": "Polioviruses as indicator of virological quality of water.", "content": "Viruses were found in 47 out of 53 samples of raw domestic sewage collected over a 13-month period from a high socioeconomic level community. At least 39 out of these 47 samples contained polioviruses as was expected in a population where children were receiving Sabin live-attenuated vaccine. Polioviruses could then be used as a suitable indicator of the virological quality of water in communities where Sabin vaccine is used.", "contents": "Polioviruses as indicator of virological quality of water. Viruses were found in 47 out of 53 samples of raw domestic sewage collected over a 13-month period from a high socioeconomic level community. At least 39 out of these 47 samples contained polioviruses as was expected in a population where children were receiving Sabin live-attenuated vaccine. Polioviruses could then be used as a suitable indicator of the virological quality of water in communities where Sabin vaccine is used."}
{"id": "PMID:231480", "title": "Aggregation during sexual development in Dictyostelium discoideum.", "content": "A microcinematographic analysis of the behaviour and movements of cells and cell masses in mated cultures (NC4 X VI2) of Dictyostelium discoideum indicates that a chemotactic process directs cell aggregation during macrocyst development. Zygote giant cells form before aggregation begins and act as the aggregation centres. Young multicellular macrocyst stages are sources of cyclic AMP, and amoebae from macrocyst cultures orient chemotactically to cyclic AMP. The data, coupled with other characteristics such as pulsatile streaming, suggest that the aggregation process leading to macrycyst development is the same as that occurring during fruit construction. Other aspects of sexual development are also discussed. Based upon these data, we propose a model for the sequence of events leading to macrocyst development in D. discoideum.", "contents": "Aggregation during sexual development in Dictyostelium discoideum. A microcinematographic analysis of the behaviour and movements of cells and cell masses in mated cultures (NC4 X VI2) of Dictyostelium discoideum indicates that a chemotactic process directs cell aggregation during macrocyst development. Zygote giant cells form before aggregation begins and act as the aggregation centres. Young multicellular macrocyst stages are sources of cyclic AMP, and amoebae from macrocyst cultures orient chemotactically to cyclic AMP. The data, coupled with other characteristics such as pulsatile streaming, suggest that the aggregation process leading to macrycyst development is the same as that occurring during fruit construction. Other aspects of sexual development are also discussed. Based upon these data, we propose a model for the sequence of events leading to macrocyst development in D. discoideum."}
{"id": "PMID:231481", "title": "Serological incidence of avian reovirus infection in broiler-breeders and progeny in Nova Scotia.", "content": "The plaque neutralization test and the agar gel precipitation test were used to detect neutralizing and precipitating antibody to avian reovirus strain WVU2937 in sera from 14 commercial broiler breeder flocks and eight progeny flocks. Ten breeder flocks (71%) possessed positive agar gel precipitation reactors (598 sera tested) and 12 (86%) possessed plaque neutralization reactors (114 serum pools tested). All broiler flocks possessed agar gel precipitation reactors, but these were not examined for neutralizing antibody. As no avian reovirus vaccine had been used in Canada prior to this survey these reactions were presumably due to natural infection. Clinical evidence suggested that such infection was asymptomatic in most cases. The development and persistence of antibody to reovirus strain WVU2937 was followed in chicks exposed to the virus by oral inoculation or by contact. Neutralizing antibody was demonstrated in all birds by postinoculation day 17 and this persisted for at least six months. Precipitating antibody was also demonstrated in most chicks by postinoculation day 17, but by six months only 12% of the chicks were still agar gel precipitation positive.", "contents": "Serological incidence of avian reovirus infection in broiler-breeders and progeny in Nova Scotia. The plaque neutralization test and the agar gel precipitation test were used to detect neutralizing and precipitating antibody to avian reovirus strain WVU2937 in sera from 14 commercial broiler breeder flocks and eight progeny flocks. Ten breeder flocks (71%) possessed positive agar gel precipitation reactors (598 sera tested) and 12 (86%) possessed plaque neutralization reactors (114 serum pools tested). All broiler flocks possessed agar gel precipitation reactors, but these were not examined for neutralizing antibody. As no avian reovirus vaccine had been used in Canada prior to this survey these reactions were presumably due to natural infection. Clinical evidence suggested that such infection was asymptomatic in most cases. The development and persistence of antibody to reovirus strain WVU2937 was followed in chicks exposed to the virus by oral inoculation or by contact. Neutralizing antibody was demonstrated in all birds by postinoculation day 17 and this persisted for at least six months. Precipitating antibody was also demonstrated in most chicks by postinoculation day 17, but by six months only 12% of the chicks were still agar gel precipitation positive."}
{"id": "PMID:231487", "title": "Synthesis of choline and ethanolamine phospholipids with thiophosphoester bonds as substrates for phospholipase C.", "content": "Spectrophotometric assays of esterases are sensitive, rapid, and quite specific when thioester substrates are used. Glycerophospholipids with thiophosphoester bonds may be useful as substrates for phospholipase C (EC 3.1.4.3). These have been made from mercaptoglycerol and mercaptoethanol. The thiols were oxidized to disulfides, acylated, and reduced with dithiothreitol. Phosphocholine derivatives were made by the classical methods for oxyphosphoesters. The phosphatidyl choline analogue was converted to the phosphatidyl ethanolamine analogue by transphosphatidylation with cabbage phospholipase D and ethanolamine. Structures were proved with enzymic hydrolysis, infrared spectra, TLC behavior, and elemental analyses. The synthesized compounds were rac-1-S-phosphocholine-2,3-O-didecanoyl-1-mercapto-2,3-propanediol, 1-S-phosphoethanolamine-2,3-O-didecanoyl-1-mercapto-2,3-propanediol, and 1-S-phosphocholine-2-O-hexadecanoyl-1-mercapto-2-ethanol.", "contents": "Synthesis of choline and ethanolamine phospholipids with thiophosphoester bonds as substrates for phospholipase C. Spectrophotometric assays of esterases are sensitive, rapid, and quite specific when thioester substrates are used. Glycerophospholipids with thiophosphoester bonds may be useful as substrates for phospholipase C (EC 3.1.4.3). These have been made from mercaptoglycerol and mercaptoethanol. The thiols were oxidized to disulfides, acylated, and reduced with dithiothreitol. Phosphocholine derivatives were made by the classical methods for oxyphosphoesters. The phosphatidyl choline analogue was converted to the phosphatidyl ethanolamine analogue by transphosphatidylation with cabbage phospholipase D and ethanolamine. Structures were proved with enzymic hydrolysis, infrared spectra, TLC behavior, and elemental analyses. The synthesized compounds were rac-1-S-phosphocholine-2,3-O-didecanoyl-1-mercapto-2,3-propanediol, 1-S-phosphoethanolamine-2,3-O-didecanoyl-1-mercapto-2,3-propanediol, and 1-S-phosphocholine-2-O-hexadecanoyl-1-mercapto-2-ethanol."}
{"id": "PMID:231491", "title": "Relationship between plasma prolactin concentration and pituitary function in patients with a pituitary adenoma.", "content": "The influence of hyperprolactinaemia on endocrine functions in forty-two consecutive patients with untreated pituitary tumours was studied. Patients with acromegaly, Cushing's disease and Nelson's syndrome were excluded. Sixteen patients (eleven men and five women) had a pituitary adenoma with suprasellar extension and twenty-six (eleven men and fifteen women) had a small intrasellar tumour. Basal plasma prolactin concentration was measured in all. Thyroid function was assessed by plasma thyroxine (T4) and TSH concentrations, adrenocortical function and growth hormone (GH) secretion by the maximum plasma cortisol, adrenocorticotrophin (ACTH) and GH concentrations, respectively, during insulin-induced hypoglycaemia (tITT). Gonadal function was studied by measuring plasma concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), oestradiol-17 beta and in men, testosterone. On the basis of computer assisted tomography of the sella turcica, the tumour volume was calculated. The basal plasma prolactin concentration was elevated in 69% of the patients. Decreased GH secretion was the most frequent pituitary dysfunction (78%) followed in men by gonadal insufficiency (77%), adrenocortical insufficiency (31%) and thyroid insufficiency (21%). There was no difference between patients with elevated and normal plasma prolactin concentration as to the tumour volume and any of the endocrine variables.", "contents": "Relationship between plasma prolactin concentration and pituitary function in patients with a pituitary adenoma. The influence of hyperprolactinaemia on endocrine functions in forty-two consecutive patients with untreated pituitary tumours was studied. Patients with acromegaly, Cushing's disease and Nelson's syndrome were excluded. Sixteen patients (eleven men and five women) had a pituitary adenoma with suprasellar extension and twenty-six (eleven men and fifteen women) had a small intrasellar tumour. Basal plasma prolactin concentration was measured in all. Thyroid function was assessed by plasma thyroxine (T4) and TSH concentrations, adrenocortical function and growth hormone (GH) secretion by the maximum plasma cortisol, adrenocorticotrophin (ACTH) and GH concentrations, respectively, during insulin-induced hypoglycaemia (tITT). Gonadal function was studied by measuring plasma concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), oestradiol-17 beta and in men, testosterone. On the basis of computer assisted tomography of the sella turcica, the tumour volume was calculated. The basal plasma prolactin concentration was elevated in 69% of the patients. Decreased GH secretion was the most frequent pituitary dysfunction (78%) followed in men by gonadal insufficiency (77%), adrenocortical insufficiency (31%) and thyroid insufficiency (21%). There was no difference between patients with elevated and normal plasma prolactin concentration as to the tumour volume and any of the endocrine variables."}
{"id": "PMID:231488", "title": "[Generalized and lethal pentastomiasis due to Armillifer grandis (Hett, 1915)].", "content": "The authors described a case of generalised and lethal Pentastomiasis by a five years old girl. The most heavy parasitised organs are the lungs and the brain. Considering the age of the child and the uncommon density of the parasites, the authors suggest that the symptoms may follow the casual ingestion of a gravid female worm.", "contents": "[Generalized and lethal pentastomiasis due to Armillifer grandis (Hett, 1915)]. The authors described a case of generalised and lethal Pentastomiasis by a five years old girl. The most heavy parasitised organs are the lungs and the brain. Considering the age of the child and the uncommon density of the parasites, the authors suggest that the symptoms may follow the casual ingestion of a gravid female worm."}
{"id": "PMID:231492", "title": "Variable effect on peripheral blood leucocytes during JE virus infection of man.", "content": "The peripheral blood leucocytes of twenty-four cases of Japanese encephalitis (JE) were studied and the findings were compared with those in twenty-five normal health controls of matching age and sex. In the early phases of the disease marked neutrophil leucocytosis was seen which returned to almost normal levels by the fourth week. Lymphopenia was associated with diminished T lymphocytes but the number of B lymphocytes remained within the normal range. Though the number of T lymphocytes was reduced, their function of leucocyte migration inhibition in the presence of JE virus antigen was significantly higher. The phagocytic activity of the neutrophils, as shown by the uptake of neutral red dye, was diminished but the phagocytic activity of monocytes as shown by the uptake of neutral red dye, was diminished but the phagocytic activity of monocytes as shown by the uptake of neutral red dye or ingestion of latex particles remained unaffected. HI antibodies against JE virus were significantly higher in cases of encephalitis as compared with the control group. Thus, JE virus infection in man has a variable effect on different components of the peripheral blood leucocytes.", "contents": "Variable effect on peripheral blood leucocytes during JE virus infection of man. The peripheral blood leucocytes of twenty-four cases of Japanese encephalitis (JE) were studied and the findings were compared with those in twenty-five normal health controls of matching age and sex. In the early phases of the disease marked neutrophil leucocytosis was seen which returned to almost normal levels by the fourth week. Lymphopenia was associated with diminished T lymphocytes but the number of B lymphocytes remained within the normal range. Though the number of T lymphocytes was reduced, their function of leucocyte migration inhibition in the presence of JE virus antigen was significantly higher. The phagocytic activity of the neutrophils, as shown by the uptake of neutral red dye, was diminished but the phagocytic activity of monocytes as shown by the uptake of neutral red dye, was diminished but the phagocytic activity of monocytes as shown by the uptake of neutral red dye or ingestion of latex particles remained unaffected. HI antibodies against JE virus were significantly higher in cases of encephalitis as compared with the control group. Thus, JE virus infection in man has a variable effect on different components of the peripheral blood leucocytes."}
{"id": "PMID:231493", "title": "Osseous lesions and pathologic fractures in congenital cytomegalic inclusion disease: report of a case.", "content": "A newborn infant with congenital cytomegalic inclusion disease had spontaneous fractures of the distal radii bilaterally, and involvement of the metaphyseal portions of the humeri, ulnas, femurs, and tibias. The fractures healed promptly without complications under ordinary management. At the present time, one can only speculate on the cause of these lesions. Viral osteomyelitis, osteomalacia secondary to hepatitis and malabsorption and a disturbance of endochondral ossification are all possibilities. There is a need for additional cases with histologic and biochemical studies of the bone lesions in congenital cytomegalic inclusion disease.", "contents": "Osseous lesions and pathologic fractures in congenital cytomegalic inclusion disease: report of a case. A newborn infant with congenital cytomegalic inclusion disease had spontaneous fractures of the distal radii bilaterally, and involvement of the metaphyseal portions of the humeri, ulnas, femurs, and tibias. The fractures healed promptly without complications under ordinary management. At the present time, one can only speculate on the cause of these lesions. Viral osteomyelitis, osteomalacia secondary to hepatitis and malabsorption and a disturbance of endochondral ossification are all possibilities. There is a need for additional cases with histologic and biochemical studies of the bone lesions in congenital cytomegalic inclusion disease."}
{"id": "PMID:231496", "title": "In vivo transcription and translation of R-plasmid 538-1 DNA in Escherichia coli.", "content": "In vivo transcription and translation of R-plasmid 538-1 in E. coli was analyzed. Transcription of individual restriction fragments was determined qualitatively by utilizing the techniques developed by Southern (27), and quantitatively by carrying out DNA-RNA filter hybridization. The most active region of R-plasmid transcription in strains repressed for conjugal transfer was found to occur in the region of the R-plasmid carrying the antibiotic resistance genes. In plasmids derepressed for conjugal transfer, a high level of transcription from the transfer gene region was also observed. When strains carrying R538-1drd were induced with Hg++ a high level of transcription was observed from the region of the R-plasmid carrying the genes for Hgr. Hybrid ColE1 plasmids carrying restriction fragments from the antibiotic resistance region of R538-1 were segregated into minicells. Labeling of the minicells with 35S-methionine allowed identification of the proteins coded by the fragments. A limited number of proteins were detected, and several of these have been correlated with the antibiotic resistance genes carried by R538-1.", "contents": "In vivo transcription and translation of R-plasmid 538-1 DNA in Escherichia coli. In vivo transcription and translation of R-plasmid 538-1 in E. coli was analyzed. Transcription of individual restriction fragments was determined qualitatively by utilizing the techniques developed by Southern (27), and quantitatively by carrying out DNA-RNA filter hybridization. The most active region of R-plasmid transcription in strains repressed for conjugal transfer was found to occur in the region of the R-plasmid carrying the antibiotic resistance genes. In plasmids derepressed for conjugal transfer, a high level of transcription from the transfer gene region was also observed. When strains carrying R538-1drd were induced with Hg++ a high level of transcription was observed from the region of the R-plasmid carrying the genes for Hgr. Hybrid ColE1 plasmids carrying restriction fragments from the antibiotic resistance region of R538-1 were segregated into minicells. Labeling of the minicells with 35S-methionine allowed identification of the proteins coded by the fragments. A limited number of proteins were detected, and several of these have been correlated with the antibiotic resistance genes carried by R538-1."}
{"id": "PMID:231497", "title": "The exploitation of lambda tra transducing phages in the study of bacterial conjugation.", "content": "A set of lambda tra transducing phages have been isolated from an abnormal lysogen in which the lambda prophage was inserted into the traB gene of Flac, and characterised both genetically and physicochemically. The phages were used in several ways to facilitate studies of bacterial conjugation: (a) they aided the identification and mapping of four new transfer genes, traU, traN, traV and traW: (b) they gave information about the location and orientation of the promoters for traM, traJ and traI: (c) a more precise physical map of the transfer region was developed from the lengths of the tra segments that they carried, and (d) the molecular weights of the traM and traJ proteins synthesised by a lambda ptraMJALEK phage were determined.", "contents": "The exploitation of lambda tra transducing phages in the study of bacterial conjugation. A set of lambda tra transducing phages have been isolated from an abnormal lysogen in which the lambda prophage was inserted into the traB gene of Flac, and characterised both genetically and physicochemically. The phages were used in several ways to facilitate studies of bacterial conjugation: (a) they aided the identification and mapping of four new transfer genes, traU, traN, traV and traW: (b) they gave information about the location and orientation of the promoters for traM, traJ and traI: (c) a more precise physical map of the transfer region was developed from the lengths of the tra segments that they carried, and (d) the molecular weights of the traM and traJ proteins synthesised by a lambda ptraMJALEK phage were determined."}
{"id": "PMID:231498", "title": "Restriction of resistance transfer in Staphylococcus aureus.", "content": "The transduction frequency of wild type resistance plasmids carrying the modification of a defined donor strain into a series of acceptor strains with different restriction systems and into restriction-deficient mutants was studied. Plasmids carrying resistance to tetracycline, chloramphenicol and penicillin were in general as sensitive as the transducing phage to restriction and modification. Plasmids carrying penicillinase of type A and C could be transferred into strains of group II.", "contents": "Restriction of resistance transfer in Staphylococcus aureus. The transduction frequency of wild type resistance plasmids carrying the modification of a defined donor strain into a series of acceptor strains with different restriction systems and into restriction-deficient mutants was studied. Plasmids carrying resistance to tetracycline, chloramphenicol and penicillin were in general as sensitive as the transducing phage to restriction and modification. Plasmids carrying penicillinase of type A and C could be transferred into strains of group II."}
{"id": "PMID:231500", "title": "Lipid accumulation in the rat liver: a histological and biochemical study.", "content": "The sequential pattern of lipid accumulation and associated biochemical changes were studied in two commonly used experimental models of nutritional fatty liver in rats. Female rats were maintained for 8 weeks on high fat, low protein diets containing adequate methionine and choline, and drinking water ad libitum (Diet 1), or deficient in methionine and choline and containing 20% ethanol as a substitute for drinking water (Diet 2). Histologically, there was a progressive increase in liver lipids, mainly in the periportal areas. Occasional foci of liver cell necrosis with lipogranuloma formation occurred in areas of severe fatty change. These changes appeared earlier and were more marked in rats maintained on Diet 2. Electron micrographs revealed large lipid droplets in the liver cells, which sometimes contained myelin figures. The mitochondria were enlarged, distorted and appeared as amorphous structures with disorientated cristae in rats on Diet 1, whereas they had a condensed conformation in rats maintained on Diet 2. Rough endoplasmic reticulum was fragmented and degranulated particularly in rats on Diet 1, and smooth endoplasmic reticulum showed hyperplasia and vesiculation in rats on Diet 2. There was a progressive increase in the total liver lipids and triglycerides in both the groups of rats. This fatty change was accompanied by a significant increase in hepatic 3-hydroxybutyrate, acetoacetate, malate, 2-oxoglutarate, citrate, lactate, ammonia, glutamate, alanine and aspartate, and a significant decrease in oxaloacetate, urea and glucose concentrations. The mass action ratios for alanine aminotransferase, aspartate amino transferase, and glutamate dehydrogenase, generally moved in a parallel direction. Hepatic ATP content was considerably reduced accompanied by a decrease in [ATP]/[ADP] ratios and a significant increased in [lactate]/[pyruvate] and [3-hydroxybutyrate]/[acetoacetate] ratios. There was a corresponding decrease in the [NAD+]/[NADH] ratios both in the cytoplasmic and mitochondrial compartments. These biochemical changes were particularly severe in rats maintained on Diet 1 and Diet 2 for 8 weeks. There was a very good relationship between impaired mitochondrial and endoplasmic reticulum functions, redox and phosphorylation states, and the relevance of their changes to the fate of fatty liver cells.", "contents": "Lipid accumulation in the rat liver: a histological and biochemical study. The sequential pattern of lipid accumulation and associated biochemical changes were studied in two commonly used experimental models of nutritional fatty liver in rats. Female rats were maintained for 8 weeks on high fat, low protein diets containing adequate methionine and choline, and drinking water ad libitum (Diet 1), or deficient in methionine and choline and containing 20% ethanol as a substitute for drinking water (Diet 2). Histologically, there was a progressive increase in liver lipids, mainly in the periportal areas. Occasional foci of liver cell necrosis with lipogranuloma formation occurred in areas of severe fatty change. These changes appeared earlier and were more marked in rats maintained on Diet 2. Electron micrographs revealed large lipid droplets in the liver cells, which sometimes contained myelin figures. The mitochondria were enlarged, distorted and appeared as amorphous structures with disorientated cristae in rats on Diet 1, whereas they had a condensed conformation in rats maintained on Diet 2. Rough endoplasmic reticulum was fragmented and degranulated particularly in rats on Diet 1, and smooth endoplasmic reticulum showed hyperplasia and vesiculation in rats on Diet 2. There was a progressive increase in the total liver lipids and triglycerides in both the groups of rats. This fatty change was accompanied by a significant increase in hepatic 3-hydroxybutyrate, acetoacetate, malate, 2-oxoglutarate, citrate, lactate, ammonia, glutamate, alanine and aspartate, and a significant decrease in oxaloacetate, urea and glucose concentrations. The mass action ratios for alanine aminotransferase, aspartate amino transferase, and glutamate dehydrogenase, generally moved in a parallel direction. Hepatic ATP content was considerably reduced accompanied by a decrease in [ATP]/[ADP] ratios and a significant increased in [lactate]/[pyruvate] and [3-hydroxybutyrate]/[acetoacetate] ratios. There was a corresponding decrease in the [NAD+]/[NADH] ratios both in the cytoplasmic and mitochondrial compartments. These biochemical changes were particularly severe in rats maintained on Diet 1 and Diet 2 for 8 weeks. There was a very good relationship between impaired mitochondrial and endoplasmic reticulum functions, redox and phosphorylation states, and the relevance of their changes to the fate of fatty liver cells."}
{"id": "PMID:231507", "title": "Significance of biochemical markers in Morbus Hodgkin.", "content": "Statistically significant changes of the values of biochemical tests can be utilized in complex clinical and laboratory diagnosis and in appreciating the status of the disease in Hodgkin's lymphomas. Considering the increasing number of biochemical tests and their common nonspecificity, urgent necessity appears to verify their importance in malignant diseases. The authors analyzed 2626 biochemical examinations in 39 patients with M. Hodgkin. The results were evaluated in untreated patients, in patients in remission with and without BCG vaccination, in relapse, in the course of successful and unsuccessful therapy and the contribution of individual laboratory tests for the diagnosis and the course of the disease was verified. Suitable for the diagnosis are those tests which do not deviate from physiological limits in the sense either of the increase (alpha 2-, beta-, gamma-globulins and transaminases) or the decrease (albumins and albumin-globulin quotient). Statistically insignificant were the changes of the values of total protein, alpha1-globulins, N-urea, thymol turbidity reaction, cholesterol, phosphatases and lactate dehydrogenase. The results presented can be an aid for the clinician in the choice of individual biochemical markers.", "contents": "Significance of biochemical markers in Morbus Hodgkin. Statistically significant changes of the values of biochemical tests can be utilized in complex clinical and laboratory diagnosis and in appreciating the status of the disease in Hodgkin's lymphomas. Considering the increasing number of biochemical tests and their common nonspecificity, urgent necessity appears to verify their importance in malignant diseases. The authors analyzed 2626 biochemical examinations in 39 patients with M. Hodgkin. The results were evaluated in untreated patients, in patients in remission with and without BCG vaccination, in relapse, in the course of successful and unsuccessful therapy and the contribution of individual laboratory tests for the diagnosis and the course of the disease was verified. Suitable for the diagnosis are those tests which do not deviate from physiological limits in the sense either of the increase (alpha 2-, beta-, gamma-globulins and transaminases) or the decrease (albumins and albumin-globulin quotient). Statistically insignificant were the changes of the values of total protein, alpha1-globulins, N-urea, thymol turbidity reaction, cholesterol, phosphatases and lactate dehydrogenase. The results presented can be an aid for the clinician in the choice of individual biochemical markers."}
{"id": "PMID:231508", "title": "E rosettes in the uranium miners with lung cancer.", "content": "Rosette forming cells (RFC) were evaluated in the peripheral blood of healthy persons, patients with lung cancer and chronic bronchitis. Simultaneously the levels of RFC in persons with and without radiation exposure were compared. Two types of rosettes were enumerated: 1) lymphocytes binding 1 or 2 sheep red blood cells (SRBC), 2) lymphocytes binding 3 or more SRBC. Then the sum of both types was calculated. The patients with lung cancer were divided according to the TNM classification and histological types. The relative and absolute numbers of RFC in 1 microliter of peripheral blood proved depressed capacity of peripheral T-lymphocytes to form rosettes not only in patients with cancer or chronic bronchitis but also in controls with radiation exposure. Furthermore, there was established that the control group with radiation exposure was not different from the patients with cancer or chronic bronchitis.", "contents": "E rosettes in the uranium miners with lung cancer. Rosette forming cells (RFC) were evaluated in the peripheral blood of healthy persons, patients with lung cancer and chronic bronchitis. Simultaneously the levels of RFC in persons with and without radiation exposure were compared. Two types of rosettes were enumerated: 1) lymphocytes binding 1 or 2 sheep red blood cells (SRBC), 2) lymphocytes binding 3 or more SRBC. Then the sum of both types was calculated. The patients with lung cancer were divided according to the TNM classification and histological types. The relative and absolute numbers of RFC in 1 microliter of peripheral blood proved depressed capacity of peripheral T-lymphocytes to form rosettes not only in patients with cancer or chronic bronchitis but also in controls with radiation exposure. Furthermore, there was established that the control group with radiation exposure was not different from the patients with cancer or chronic bronchitis."}
{"id": "PMID:231510", "title": "Soluble and membrane-bound protein kinases in newborn and mature rat brain.", "content": "We studied the developmental changes of soluble and membrane-bound protein kinases (EC 2.7.1.37) in rat brain and found that the elution profiles from a DEAE-cellulose column by NaCl of adenosine-3':5'-monophosphate (cyclic AMP) dependent protein kinase from cytosol were not significantly different in newborn (0.19 M NaCl) vs. mature (0.21 M NaCl). In addition, there was little change in Kd for cyclic AMP binding of newborn and mature soluble enzyme. In contrast, using endogenous protein as the phosphate acceptor, cyclic AMP dependent and calcium-dependent protein kinases from brain synaptic membranes of mature rats were significantly higher than that of newborn rats.", "contents": "Soluble and membrane-bound protein kinases in newborn and mature rat brain. We studied the developmental changes of soluble and membrane-bound protein kinases (EC 2.7.1.37) in rat brain and found that the elution profiles from a DEAE-cellulose column by NaCl of adenosine-3':5'-monophosphate (cyclic AMP) dependent protein kinase from cytosol were not significantly different in newborn (0.19 M NaCl) vs. mature (0.21 M NaCl). In addition, there was little change in Kd for cyclic AMP binding of newborn and mature soluble enzyme. In contrast, using endogenous protein as the phosphate acceptor, cyclic AMP dependent and calcium-dependent protein kinases from brain synaptic membranes of mature rats were significantly higher than that of newborn rats."}
{"id": "PMID:231511", "title": "Postnatal activity of angiotensin converting enzyme in rat brain.", "content": "The specific activity of angiotensin converting enzyme (ACE) was studied in eight brain regions in rats 2--65 days of age. At 65 days of age the activities in various regions relative to the cortex were: neostriatum, 1,200%; hippocampus/amygdala, 430%; hypothalamus, 190%; cerebellum, 140%; and midbrain, thalamus and pons/medulla, 110%. Significant linear increases were found in the neostriatum, hippocampus/amygdala and cortex at 2--65 days of age, in the pons/medulla and thalamus at 2--42 days of age and in the midbrain at 2--21 days of age. The increase with age was greatest in the neostriatum and the data are consistent with the occurrence of ACE in neurons in this area.", "contents": "Postnatal activity of angiotensin converting enzyme in rat brain. The specific activity of angiotensin converting enzyme (ACE) was studied in eight brain regions in rats 2--65 days of age. At 65 days of age the activities in various regions relative to the cortex were: neostriatum, 1,200%; hippocampus/amygdala, 430%; hypothalamus, 190%; cerebellum, 140%; and midbrain, thalamus and pons/medulla, 110%. Significant linear increases were found in the neostriatum, hippocampus/amygdala and cortex at 2--65 days of age, in the pons/medulla and thalamus at 2--42 days of age and in the midbrain at 2--21 days of age. The increase with age was greatest in the neostriatum and the data are consistent with the occurrence of ACE in neurons in this area."}
{"id": "PMID:231513", "title": "Cerebral blood flow and sleep state in the normal newborn infant.", "content": "The cerebral blood flow (CBF) index measured by venous occlusion plethysmography in 12 normal newborn infants was found to vary significantly with sleep state. Criteria for definition of sleep state are described. The cerebral blood flow index in active sleep was 23% higher than in quiet sleep, and there were smaller, but consistent and significant, differences between intermediate and active or quiet sleep.", "contents": "Cerebral blood flow and sleep state in the normal newborn infant. The cerebral blood flow (CBF) index measured by venous occlusion plethysmography in 12 normal newborn infants was found to vary significantly with sleep state. Criteria for definition of sleep state are described. The cerebral blood flow index in active sleep was 23% higher than in quiet sleep, and there were smaller, but consistent and significant, differences between intermediate and active or quiet sleep."}
{"id": "PMID:231514", "title": "Gluconeogenic key enzymes in normal and intrauterine growth-retarded newborn rats.", "content": "Intrauterine growth retardation was induced in rats by ligation of the artery of one of both uterine horns. Activities of pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1,6-diphosphatase and glucose-6-phosphatase in liver were measured at 0, 1, 3 and 6 h after delivery in newborn rats from normal and sham-operated litters, and from ligated and contralateral uterine horns. Lower activities of fructose-1,6-diphosphatase were found in small-for-gestational-age animals in comparison with animals from contralateral horns. When small-for-gestational-age animals were compared with animals from sham litters (which could be regarded as more satisfactory controls), the activities of two other gluconeogenic enzymes (pyruvate carboxylase and glucose-6-phosphatase) appeared to be lower as well. It is concluded that a delay in the development of these gluconeogenic enzymes could play a role in neonatal hypoglycemia in small-for-gestational-age rats.", "contents": "Gluconeogenic key enzymes in normal and intrauterine growth-retarded newborn rats. Intrauterine growth retardation was induced in rats by ligation of the artery of one of both uterine horns. Activities of pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1,6-diphosphatase and glucose-6-phosphatase in liver were measured at 0, 1, 3 and 6 h after delivery in newborn rats from normal and sham-operated litters, and from ligated and contralateral uterine horns. Lower activities of fructose-1,6-diphosphatase were found in small-for-gestational-age animals in comparison with animals from contralateral horns. When small-for-gestational-age animals were compared with animals from sham litters (which could be regarded as more satisfactory controls), the activities of two other gluconeogenic enzymes (pyruvate carboxylase and glucose-6-phosphatase) appeared to be lower as well. It is concluded that a delay in the development of these gluconeogenic enzymes could play a role in neonatal hypoglycemia in small-for-gestational-age rats."}
{"id": "PMID:231515", "title": "The ultrastructure of the pituitary gland under chronic stimulation of the ACTH-cells in human pathology and animal experiments.", "content": "Chronic stimulation of the ACTH-cells in rats was undertaken by adrenalectomy, chemical adrenostasis, by application of a CRF-analog and by non-specific means. The ultrastructural findings of the ACTH-cells were compared to those of the human pituitary gland in Cushing's disease. The pituitaries of 12 patients with the hypothalamic-hypophyseal form of Cushing's syndrome were studied by electron microscopy. A good correlation of the experimental observations to those in human pathology could be seen in the first steps of reaction. There was an enlargement of the ACTH-cells with well developed organelles and there was a simple hyperplasia. The following forms of reaction, nodular hyperplasia and adenomas, were only observed in the human pituitary glands. Chronic suppression by steroids leads to a diminution of the single ACTH-cell and their organelles and a reduction. The appearance of Crooke's cells is specific for the human pituitary and is not reproduced in animal experiments.", "contents": "The ultrastructure of the pituitary gland under chronic stimulation of the ACTH-cells in human pathology and animal experiments. Chronic stimulation of the ACTH-cells in rats was undertaken by adrenalectomy, chemical adrenostasis, by application of a CRF-analog and by non-specific means. The ultrastructural findings of the ACTH-cells were compared to those of the human pituitary gland in Cushing's disease. The pituitaries of 12 patients with the hypothalamic-hypophyseal form of Cushing's syndrome were studied by electron microscopy. A good correlation of the experimental observations to those in human pathology could be seen in the first steps of reaction. There was an enlargement of the ACTH-cells with well developed organelles and there was a simple hyperplasia. The following forms of reaction, nodular hyperplasia and adenomas, were only observed in the human pituitary glands. Chronic suppression by steroids leads to a diminution of the single ACTH-cell and their organelles and a reduction. The appearance of Crooke's cells is specific for the human pituitary and is not reproduced in animal experiments."}
{"id": "PMID:231518", "title": "Regulation of sterol synthesis in leukaemic blast cells: a defect resembling familial hypercholesterolaemia.", "content": "Leucocytes from normal subjects and from patients with acute myeloblastic leukaemia incubated for 9 h in the absence of lipoproteins increased their rate of sterol biosynthesis from [2-14C]acetate threefold. Subsequent addition of complete serum, low density lipoprotein or cholesterol in a non-lipoprotein form suppressed sterol synthesis in leucocytes from normal subjects. In contrast, complete serum or low density lipoprotein totally failed to suppress sterol synthesis in leukaemic blast cells. However, when these cells were incubated with cholesterol in a non-lipoprotein form suppression of sterol synthesis occurred as in normal leucocytes. These results suggest that leukaemic blast cells behave like cells from patients with familial hypercholesterolaemia in showing failure of regulation of sterol synthesis by low density lipoprotein.", "contents": "Regulation of sterol synthesis in leukaemic blast cells: a defect resembling familial hypercholesterolaemia. Leucocytes from normal subjects and from patients with acute myeloblastic leukaemia incubated for 9 h in the absence of lipoproteins increased their rate of sterol biosynthesis from [2-14C]acetate threefold. Subsequent addition of complete serum, low density lipoprotein or cholesterol in a non-lipoprotein form suppressed sterol synthesis in leucocytes from normal subjects. In contrast, complete serum or low density lipoprotein totally failed to suppress sterol synthesis in leukaemic blast cells. However, when these cells were incubated with cholesterol in a non-lipoprotein form suppression of sterol synthesis occurred as in normal leucocytes. These results suggest that leukaemic blast cells behave like cells from patients with familial hypercholesterolaemia in showing failure of regulation of sterol synthesis by low density lipoprotein."}
{"id": "PMID:231519", "title": "Plasma equilin concentrations in an oophorectomized woman following ingestion of conjugated equine oestrogens (Premarin).", "content": "The plasma equilin concentration was 25.2 nmol/l (6.7 ng/ml) 4 h after an oral dose of Premarin (1.25 mg), and a maximum concentration of 20.5 nmol/l (5.5 ng/ml) was recorded 3 h after a smaller dose (0.625 mg) was given. 24 h later, the plasma equilin was still considerable, being 6.1 nmol/l (1.6 ng/ml) and 3.7 nmol/l (1.2 ng/ml) for the larger and smaller dosages respectively. The findings for equilin are considerably higher than physiological oestrogen concentrations and in addition show that daily therapy with Premarin could lead to cumulation of the steroid.", "contents": "Plasma equilin concentrations in an oophorectomized woman following ingestion of conjugated equine oestrogens (Premarin). The plasma equilin concentration was 25.2 nmol/l (6.7 ng/ml) 4 h after an oral dose of Premarin (1.25 mg), and a maximum concentration of 20.5 nmol/l (5.5 ng/ml) was recorded 3 h after a smaller dose (0.625 mg) was given. 24 h later, the plasma equilin was still considerable, being 6.1 nmol/l (1.6 ng/ml) and 3.7 nmol/l (1.2 ng/ml) for the larger and smaller dosages respectively. The findings for equilin are considerably higher than physiological oestrogen concentrations and in addition show that daily therapy with Premarin could lead to cumulation of the steroid."}
{"id": "PMID:231520", "title": "Prevalence of antibodies to soluble antigen of Epstein-Barr virus-producing cells (P3HR-1) in the sera of hamadryas baboons of the high lymphoma incidence stock.", "content": "Soluble antigen of P3HR-1 cells (SA-P3HR-1) was identified in indirect double immunodiffusion enhanced with tannic acid using serum of a nasopharyngeal carcinoma patient containing high-titer antibodies to Epstein-Barr virus (EBV) antigens. SA-P3HR-1 was nonidentical to soluble antigen of Raji cells. Human and baboon sera containing antibodies to all the known antigen of EBV and HVP respectively were anti-SA-3HR-1-positive. Human and baboon sera containing antibodies to all the known antigens of EBV and herpesvirus Papio (HVP) were also anti-SA-P3HR-1-negative. Prevalence of anti-SA-P3HR-1 was very high in two groups of the high-lymphoma incidence stock of hamadryas baboons of the Sukhumi monkey colony. 54% (15 of 28) and 38% (13 of 34) of clinically lymphomatous and clinical normal monkeys, respectively, were anti-SA-P3HR-1-positive.. Only 1 of 30 normal baboons studied, living in the forest and having no contacts with the baboons in the main stock of the Sukhumi monkey colony, was anti-SA-P3HR-1-positive (3%).", "contents": "Prevalence of antibodies to soluble antigen of Epstein-Barr virus-producing cells (P3HR-1) in the sera of hamadryas baboons of the high lymphoma incidence stock. Soluble antigen of P3HR-1 cells (SA-P3HR-1) was identified in indirect double immunodiffusion enhanced with tannic acid using serum of a nasopharyngeal carcinoma patient containing high-titer antibodies to Epstein-Barr virus (EBV) antigens. SA-P3HR-1 was nonidentical to soluble antigen of Raji cells. Human and baboon sera containing antibodies to all the known antigen of EBV and HVP respectively were anti-SA-3HR-1-positive. Human and baboon sera containing antibodies to all the known antigens of EBV and herpesvirus Papio (HVP) were also anti-SA-P3HR-1-negative. Prevalence of anti-SA-P3HR-1 was very high in two groups of the high-lymphoma incidence stock of hamadryas baboons of the Sukhumi monkey colony. 54% (15 of 28) and 38% (13 of 34) of clinically lymphomatous and clinical normal monkeys, respectively, were anti-SA-P3HR-1-positive.. Only 1 of 30 normal baboons studied, living in the forest and having no contacts with the baboons in the main stock of the Sukhumi monkey colony, was anti-SA-P3HR-1-positive (3%)."}
{"id": "PMID:231521", "title": "Increased agglutinability and haemadsorption of Marek's disease HPRS line 1 lymphoblastoic cells after concanavalin A treatment.", "content": "The HPRS line 1 lymphoblastoid cells derived from an ovarian lymphoma induced by Marek's disease virus in chickens displayed increased agglutinability and haemadsorption when incubated with Con A. The increase was proportional to the concentration of Con A used. The same Con A-untreated cells and normal chicken lymphocytes incubated with Con A exhibited no increase in agglutinability and haemadsorption, however.", "contents": "Increased agglutinability and haemadsorption of Marek's disease HPRS line 1 lymphoblastoic cells after concanavalin A treatment. The HPRS line 1 lymphoblastoid cells derived from an ovarian lymphoma induced by Marek's disease virus in chickens displayed increased agglutinability and haemadsorption when incubated with Con A. The increase was proportional to the concentration of Con A used. The same Con A-untreated cells and normal chicken lymphocytes incubated with Con A exhibited no increase in agglutinability and haemadsorption, however."}
{"id": "PMID:231516", "title": "[Blood serum cortisol, insulin and somatotropin concentration in children with hypothalamo-hypophyseal insufficiency].", "content": "In 22 patients with restricted growth the consecutive stimulation with arginine and insuline was applied for the diagnosis of somatotropic insufficiency. 13 children showed GH insufficiency. Simultaneously cortisol level during hypoglycemia for ACTH reserve and insulin level after arginine application were estimated.", "contents": "[Blood serum cortisol, insulin and somatotropin concentration in children with hypothalamo-hypophyseal insufficiency]. In 22 patients with restricted growth the consecutive stimulation with arginine and insuline was applied for the diagnosis of somatotropic insufficiency. 13 children showed GH insufficiency. Simultaneously cortisol level during hypoglycemia for ACTH reserve and insulin level after arginine application were estimated."}
{"id": "PMID:231534", "title": "Neuropsychological dysfunction in acute viral hepatitis.", "content": "Neuropsychological dysfunction may precede, occur simultaneously with, or follow the icteric phase of viral hepatitis. Encephalitic and meningitic involvement appears to precede the onset of clinical hepatitis while the tremor syndrome usually follows the onset of illness. The Guillain-Barr\u00e9 syndrome, peripheral nerve disorders, and behavioral abnormalities may occur at any stage of the disease. Neuropsychological alterations noted during the prodrome of viral hepatitis usually clear without sequelae but abnormalities which follow the onset of jaundice may persist during the convalescent phase for prolonged periods. Neither occurrence, type, nor severity of neuropsychological dysfunction appear to be related to specific hepatitis viruses since both type B and non-B infections have been implicated. Furthermore, neuropsychological dysfunction does not appear to be related to the severity of the hepatitis as assessed by clinical or histological features. Although direct viral invasion of nervous tissue and immune complex-mediated damage have been postulated, the mechanism(s) of neuropsychological abnormalities remains to be determined.", "contents": "Neuropsychological dysfunction in acute viral hepatitis. Neuropsychological dysfunction may precede, occur simultaneously with, or follow the icteric phase of viral hepatitis. Encephalitic and meningitic involvement appears to precede the onset of clinical hepatitis while the tremor syndrome usually follows the onset of illness. The Guillain-Barr\u00e9 syndrome, peripheral nerve disorders, and behavioral abnormalities may occur at any stage of the disease. Neuropsychological alterations noted during the prodrome of viral hepatitis usually clear without sequelae but abnormalities which follow the onset of jaundice may persist during the convalescent phase for prolonged periods. Neither occurrence, type, nor severity of neuropsychological dysfunction appear to be related to specific hepatitis viruses since both type B and non-B infections have been implicated. Furthermore, neuropsychological dysfunction does not appear to be related to the severity of the hepatitis as assessed by clinical or histological features. Although direct viral invasion of nervous tissue and immune complex-mediated damage have been postulated, the mechanism(s) of neuropsychological abnormalities remains to be determined."}
{"id": "PMID:231536", "title": "Tumor cell aggregation and mode of cancer spread in linitis plastica type of gastric carcinoma.", "content": "Spread of tumor cells in linitis plastica type of gastric carcinoma was studied in relation to features of tumor cell aggregation which were classified into two types: free-cell type and small nest type. Free-cell type was accompanied by a larger amount of fibrous stroma in submucosal layers than in small nest type. In the gastric wall lymphatics and regional lymph nodes, small nest types was more prominent than the free-cell type. Lymphatic permeation was noted predominantly in the submucosa. In the mucosa, both free-cell and small nest types were frequently present. In carcinoma with free-cell type predominance, diffuse infiltration with infrequent lymphogenous spread was noted, while in carcinoma with small nest type predominance, spread via the lymphogenous route was observed more frequently. The mode of cancer spread in this type of carcinoma appeared to be affected by the type of tumor cell aggregation dominant in the mucosa.", "contents": "Tumor cell aggregation and mode of cancer spread in linitis plastica type of gastric carcinoma. Spread of tumor cells in linitis plastica type of gastric carcinoma was studied in relation to features of tumor cell aggregation which were classified into two types: free-cell type and small nest type. Free-cell type was accompanied by a larger amount of fibrous stroma in submucosal layers than in small nest type. In the gastric wall lymphatics and regional lymph nodes, small nest types was more prominent than the free-cell type. Lymphatic permeation was noted predominantly in the submucosa. In the mucosa, both free-cell and small nest types were frequently present. In carcinoma with free-cell type predominance, diffuse infiltration with infrequent lymphogenous spread was noted, while in carcinoma with small nest type predominance, spread via the lymphogenous route was observed more frequently. The mode of cancer spread in this type of carcinoma appeared to be affected by the type of tumor cell aggregation dominant in the mucosa."}
{"id": "PMID:231537", "title": "Histopathological studies on renal tubular cell tumors in rats treated with N-ethyl-N-hydroxyethylnitrosamine.", "content": "Administration of a diet containing 0.2% N-ethyl-N-hydroxyethylnitrosamine (EHEN) for 2 weeks induced hepatocellular carcinoma in 3 and renal tubular cell tumors in 7 of 9 Wistar rats. Diet containing 0.1% EHEN induced renal tubular cell tumors in 6 of 10 rats, but no hepatocellular carcinomas. Both diets induced atypical cell population of tubules in the kidney, but no nephroblastoma.", "contents": "Histopathological studies on renal tubular cell tumors in rats treated with N-ethyl-N-hydroxyethylnitrosamine. Administration of a diet containing 0.2% N-ethyl-N-hydroxyethylnitrosamine (EHEN) for 2 weeks induced hepatocellular carcinoma in 3 and renal tubular cell tumors in 7 of 9 Wistar rats. Diet containing 0.1% EHEN induced renal tubular cell tumors in 6 of 10 rats, but no hepatocellular carcinomas. Both diets induced atypical cell population of tubules in the kidney, but no nephroblastoma."}
{"id": "PMID:231538", "title": "Sensitive and rapid method for determination of superoxide-generating activity of blood monocytes and its use as a probe for monocyte function in cancer patients.", "content": "The superoxide anion-generating capacity of human blood monocytes was measured by a sensitive and rapid method established by taking advantage of the fact that the generation of superoxide anions by monocytes was markedly enhanced by the combined stimulation of the cells with cytochalasin-E and wheat germ agglutinin. The activity was expressed by the initial rate of cytochrome c reduction after the addition of wheat germ agglutinin. The rate obtained with normal human monocytes was 0.73 +/- 0.19 nmol/min/10(5) monocytes (mean +/- SD, n = 10). Because of its sensitivity, the method required only 10(5) monocytes and can be used to follow the monocyte function in various patients. Preliminary data obtained with 15 cases of advanced cancer patients (0.29 +/- 0.10 nmol/min/10(5) monocytes) suggested a possible decrease of the superoxide-generating activity, at least in some state of cancer patients. It appears that measurement of superoxide-generating activity will be meaningful to monitor monocyte function.", "contents": "Sensitive and rapid method for determination of superoxide-generating activity of blood monocytes and its use as a probe for monocyte function in cancer patients. The superoxide anion-generating capacity of human blood monocytes was measured by a sensitive and rapid method established by taking advantage of the fact that the generation of superoxide anions by monocytes was markedly enhanced by the combined stimulation of the cells with cytochalasin-E and wheat germ agglutinin. The activity was expressed by the initial rate of cytochrome c reduction after the addition of wheat germ agglutinin. The rate obtained with normal human monocytes was 0.73 +/- 0.19 nmol/min/10(5) monocytes (mean +/- SD, n = 10). Because of its sensitivity, the method required only 10(5) monocytes and can be used to follow the monocyte function in various patients. Preliminary data obtained with 15 cases of advanced cancer patients (0.29 +/- 0.10 nmol/min/10(5) monocytes) suggested a possible decrease of the superoxide-generating activity, at least in some state of cancer patients. It appears that measurement of superoxide-generating activity will be meaningful to monitor monocyte function."}
{"id": "PMID:231539", "title": "A mutator affecting the region of the iso-1-cytochrome c gene in yeast.", "content": "The mutator gene DEL1 in the yeast Saccharomyces cerevisiae causes a high rate of formation of multisite mutations that encompass the following three adjacent genes: CYC1, which determines the structure of iso-1-cytochrome c; RAD7, which controls UV sensitivity; and OSM1, which controls osomotic sensitivity. The simplest hypothesis is that these multisite mutations are deletions, although it has not been excluded that they may involve other types of gross chromosomal aberrations. In contrast, normal strains do not produce such multisite mutations even after mutagenic treatments. The multisite mutations arise at a rate of approximately 10(-5) to 10(-6) per cell per division in DEL1 strains, which is much higher than rates observed for mutation of genes in normal strains. For example, normal strains produce all types of cyc1 mutants at a low rate of approximately 10(-8) to 10(-9). No evidence for multisite mutations was obtained upon analysis of numerous spontaneous ade1, ade2, met2 and met15 mutants isolated in a DEL1 strain. DEL1 appears to be both cis- and trans-dominant. The location of the DEL1 gene and the lack of effect on other genes suggest that the mutator acts only on a region adjacent to itself.", "contents": "A mutator affecting the region of the iso-1-cytochrome c gene in yeast. The mutator gene DEL1 in the yeast Saccharomyces cerevisiae causes a high rate of formation of multisite mutations that encompass the following three adjacent genes: CYC1, which determines the structure of iso-1-cytochrome c; RAD7, which controls UV sensitivity; and OSM1, which controls osomotic sensitivity. The simplest hypothesis is that these multisite mutations are deletions, although it has not been excluded that they may involve other types of gross chromosomal aberrations. In contrast, normal strains do not produce such multisite mutations even after mutagenic treatments. The multisite mutations arise at a rate of approximately 10(-5) to 10(-6) per cell per division in DEL1 strains, which is much higher than rates observed for mutation of genes in normal strains. For example, normal strains produce all types of cyc1 mutants at a low rate of approximately 10(-8) to 10(-9). No evidence for multisite mutations was obtained upon analysis of numerous spontaneous ade1, ade2, met2 and met15 mutants isolated in a DEL1 strain. DEL1 appears to be both cis- and trans-dominant. The location of the DEL1 gene and the lack of effect on other genes suggest that the mutator acts only on a region adjacent to itself."}
{"id": "PMID:231540", "title": "The BAM H1 restriction site in the bacteriophage T4 chromosome is located in or near gene 8.", "content": "Bacteriophage T4 cytosine-containing DNA is cleaved at a single site by the restriction endonuclease, Bam H1. The site lies within the late region of the T4 genome, close to, or within, gene 8, one of the structural genes of the phage particle baseplate.", "contents": "The BAM H1 restriction site in the bacteriophage T4 chromosome is located in or near gene 8. Bacteriophage T4 cytosine-containing DNA is cleaved at a single site by the restriction endonuclease, Bam H1. The site lies within the late region of the T4 genome, close to, or within, gene 8, one of the structural genes of the phage particle baseplate."}
{"id": "PMID:231541", "title": "Clustered arg genes on a BamHI segment of the Escherichia coli chromosome.", "content": "BamHI cleavage of DNAs from transducing phages gamma darg13 (ppc, argECBH, bfe), gamma darg14 (ppc, argECBH) and gamma darg23 (argECBH) yields three purely gamma DNA segments (and, in one case, a fourth), as well as several Excherichia coli-DNA-containing segments. The length (in kilobases, kb) of the segments, determined by electron microscopy and ararose gel electrophoresis is 4.2, 7.5, 8.4, 6.2, 6.9, and 6.4 kb for gamma darg13; 13.0, 7.5, 4.7, 6.2, 6.9, and 6.4 kb for gamma darg 14: and 5.3, 11.0, 4.7, 6.2, 6.9, and 6.4 kb for gamma darg23. Ordering of the segments (in relation to the gamma genetic map and with the direction from left to right corresponding to the clockwise orientation of the E. coli genetic map and to each of the numerical sequences given) reveals, on 26 kb of bacterial DNA, two cleavage sites defining the 7.5-kb segment obtainable from the DNA of either gamam darg13 or gamma darg14. These and analogous findings with argEC and argCB deletion-bearing strains, together with results from heteroduplex experiments, locate argE, argC, argB, and presumably argH on the 7.5-kb segment.", "contents": "Clustered arg genes on a BamHI segment of the Escherichia coli chromosome. BamHI cleavage of DNAs from transducing phages gamma darg13 (ppc, argECBH, bfe), gamma darg14 (ppc, argECBH) and gamma darg23 (argECBH) yields three purely gamma DNA segments (and, in one case, a fourth), as well as several Excherichia coli-DNA-containing segments. The length (in kilobases, kb) of the segments, determined by electron microscopy and ararose gel electrophoresis is 4.2, 7.5, 8.4, 6.2, 6.9, and 6.4 kb for gamma darg13; 13.0, 7.5, 4.7, 6.2, 6.9, and 6.4 kb for gamma darg 14: and 5.3, 11.0, 4.7, 6.2, 6.9, and 6.4 kb for gamma darg23. Ordering of the segments (in relation to the gamma genetic map and with the direction from left to right corresponding to the clockwise orientation of the E. coli genetic map and to each of the numerical sequences given) reveals, on 26 kb of bacterial DNA, two cleavage sites defining the 7.5-kb segment obtainable from the DNA of either gamam darg13 or gamma darg14. These and analogous findings with argEC and argCB deletion-bearing strains, together with results from heteroduplex experiments, locate argE, argC, argB, and presumably argH on the 7.5-kb segment."}
{"id": "PMID:231542", "title": "A new host-vector system allowing selection for foreign DNA inserts in bacteriophage lambda gtWES.", "content": "An improved vector (lambda gtWES.T5-622) for EcoRI fragments has been derived from EK2 vector lambda gtWES.lambdaB' by replacing the lambda B fragment with two identical 1.1 Md fragments from the pre-early region of bacteriophage T5. The new vector has two advantages which facilitate elimination of parental-type recombinants in an in vitro recombination experiment. Firstly, the 1.1 Md insert is too small to be re-inserted into lambda gtWES in a single copy. Secondly the 1.1 Md T5 fragment carries T5 gene A3 which prevents growth of phage retaining this fragment when the Excherichia coli host carries plasmid ColIb. Thus, essentially all plaques are due to phage with donor DNA inserts and are free of T5 DNA fragments. The size usually given as the theoretical minimum size for insertion into the lambda gt series of vectors is 0.66 Md. We have shown that this size is an underestimate and that the lower limit is about 1.6 Md. A precise estimate is difficult since there is strong selection, among phage having small inserts, for those which have acquired additional genetic material by duplication of the lambda DNA.", "contents": "A new host-vector system allowing selection for foreign DNA inserts in bacteriophage lambda gtWES. An improved vector (lambda gtWES.T5-622) for EcoRI fragments has been derived from EK2 vector lambda gtWES.lambdaB' by replacing the lambda B fragment with two identical 1.1 Md fragments from the pre-early region of bacteriophage T5. The new vector has two advantages which facilitate elimination of parental-type recombinants in an in vitro recombination experiment. Firstly, the 1.1 Md insert is too small to be re-inserted into lambda gtWES in a single copy. Secondly the 1.1 Md T5 fragment carries T5 gene A3 which prevents growth of phage retaining this fragment when the Excherichia coli host carries plasmid ColIb. Thus, essentially all plaques are due to phage with donor DNA inserts and are free of T5 DNA fragments. The size usually given as the theoretical minimum size for insertion into the lambda gt series of vectors is 0.66 Md. We have shown that this size is an underestimate and that the lower limit is about 1.6 Md. A precise estimate is difficult since there is strong selection, among phage having small inserts, for those which have acquired additional genetic material by duplication of the lambda DNA."}
{"id": "PMID:231543", "title": "The inverted terminal repetition of the DNA of weakly oncogenic adenovirus type 7.", "content": "By use of the chemical modification technique of Maxam and Gilbert (1977), the first 180 base pairs at both termini of the human adenovirus 7 genome have been determined. The results show that adenovirus 7 DNA contains a perfect inverted terminal repetition of 136 base pairs.", "contents": "The inverted terminal repetition of the DNA of weakly oncogenic adenovirus type 7. By use of the chemical modification technique of Maxam and Gilbert (1977), the first 180 base pairs at both termini of the human adenovirus 7 genome have been determined. The results show that adenovirus 7 DNA contains a perfect inverted terminal repetition of 136 base pairs."}
{"id": "PMID:231546", "title": "Stimulation of the alpha-and beta-adrenergic receptors in human ovarian vasculature in vitro.", "content": "The effect of fenoterol and norepinephrine was studied on the vascular resistance of in vitro perfused human ovary. It was found that the beta-adrenergic stimulant fenoterol causes vasodilatation, whereas the alpha-adrenergic stimulant norepinephrine elicits vasoconstriction in the arterial vascular bed of the ovary showing the role of adrenergic mechanism in the regulation of ovarian blood flow. It was supposed that therapeutical administration of beta-mimetic drugs leads to the elevation of ovarian blood flow, which may have special importance in the case of corpus luteum insufficiency.", "contents": "Stimulation of the alpha-and beta-adrenergic receptors in human ovarian vasculature in vitro. The effect of fenoterol and norepinephrine was studied on the vascular resistance of in vitro perfused human ovary. It was found that the beta-adrenergic stimulant fenoterol causes vasodilatation, whereas the alpha-adrenergic stimulant norepinephrine elicits vasoconstriction in the arterial vascular bed of the ovary showing the role of adrenergic mechanism in the regulation of ovarian blood flow. It was supposed that therapeutical administration of beta-mimetic drugs leads to the elevation of ovarian blood flow, which may have special importance in the case of corpus luteum insufficiency."}
{"id": "PMID:231551", "title": "The influence of the non-dialysable sugar-peptide fraction from bovine blood plasma on the amino acid incorporation of BHK-21 normal and RSV transformed cells.", "content": "The non-dialysable sugar-peptide rich fraction of bovine blood plasma has been studied with regard to its influence on the amino acid incorporation of BHK-21 and BHK/RSV cells in vitro. The results indicate that the Nsp fraction contains a peptide factor(s) causing changes in activity for the protein and DNA synthethizing system in both the cell cultures examined. The biological activity of the factor(s) is regulated by interaction with blood serum components and this fact may play a leading role in its regulatory function.", "contents": "The influence of the non-dialysable sugar-peptide fraction from bovine blood plasma on the amino acid incorporation of BHK-21 normal and RSV transformed cells. The non-dialysable sugar-peptide rich fraction of bovine blood plasma has been studied with regard to its influence on the amino acid incorporation of BHK-21 and BHK/RSV cells in vitro. The results indicate that the Nsp fraction contains a peptide factor(s) causing changes in activity for the protein and DNA synthethizing system in both the cell cultures examined. The biological activity of the factor(s) is regulated by interaction with blood serum components and this fact may play a leading role in its regulatory function."}
{"id": "PMID:231552", "title": "[Changes in the osmotic fragility of erythrocyte membrane in morphine- and phenobarbital-dependent rats (author's transl)].", "content": "This is apparently the first attempt to elucidate the relationship between drug dependence and the osmotic fragility of erythrocyte membrane. The osmotic fragility was measured using a coil planet centrifuge (CPC) system. Utilizing the drug-admixed food (DAF) method, rats were made drug-dependent. The osmotic fragility of morphine-dependent rats was significantly enhanced, compared with that of naive rats. By withdrawing or treating the rats with levallorphan, the osmotic fragility was enhanced more than in the morphine-dependent state. When the morphine-withdrawal rats were again given the morphine-admixed food, the osmotic fragility recovered to the morphine-dependent level. The osmotic fragility of phenobarbital-dependent rats was significantly decreased, compared with that of naive rats. On the contrary, in the phenobarbital-withdrawal rats, the osmotic fragility was significantly enhanced, compared with that of the phenobarbital-dependent rats. With re-treatment of phenobarbital-admixed food, the osmotic fragility was recovered to the levels seen in the phenobarbital-dependent rats. Abstinence signs including weight loss, decrease in food and water intake, adrenal hypertrophy etc., were observed during morphine or phenobarbital withdrawal. The effects of food or water deprivation and application of ACTH on the osmotic fragility were then studied and we found that the osmotic fragility was enhanced with these treatments. These results suggest that enhancement of osmotic fragility during withdrawal of these drugs is partly influenced by these treatments.", "contents": "[Changes in the osmotic fragility of erythrocyte membrane in morphine- and phenobarbital-dependent rats (author's transl)]. This is apparently the first attempt to elucidate the relationship between drug dependence and the osmotic fragility of erythrocyte membrane. The osmotic fragility was measured using a coil planet centrifuge (CPC) system. Utilizing the drug-admixed food (DAF) method, rats were made drug-dependent. The osmotic fragility of morphine-dependent rats was significantly enhanced, compared with that of naive rats. By withdrawing or treating the rats with levallorphan, the osmotic fragility was enhanced more than in the morphine-dependent state. When the morphine-withdrawal rats were again given the morphine-admixed food, the osmotic fragility recovered to the morphine-dependent level. The osmotic fragility of phenobarbital-dependent rats was significantly decreased, compared with that of naive rats. On the contrary, in the phenobarbital-withdrawal rats, the osmotic fragility was significantly enhanced, compared with that of the phenobarbital-dependent rats. With re-treatment of phenobarbital-admixed food, the osmotic fragility was recovered to the levels seen in the phenobarbital-dependent rats. Abstinence signs including weight loss, decrease in food and water intake, adrenal hypertrophy etc., were observed during morphine or phenobarbital withdrawal. The effects of food or water deprivation and application of ACTH on the osmotic fragility were then studied and we found that the osmotic fragility was enhanced with these treatments. These results suggest that enhancement of osmotic fragility during withdrawal of these drugs is partly influenced by these treatments."}
{"id": "PMID:231548", "title": "Surface markers and functional characteristics of human blood lymphocytes residing in the operational \"null\" subset.", "content": "After removal of nylon wool-adherent B and E rosetting T cells from the human blood lymphocyte population, a small fraction remains, often denoted as \"null\" subset. This fraction contains lymphocytes which are highly efficient in antibody-dependent and non-selective lymphocyte cytotoxicity. These cells possess markers. About half of them carry Fc receptors, and the majority has low avidity E and C3 receptors. Removal of low avidity E receptor-carrying cells did not abolish cytotoxicity to K-562 cells. The majority of cells carry receptors for Epstein-Barr virus but cannot be infected. The cells in mixed lymphocyte culture have a low reactivity. They aare stimulated by PHA and ConA to a similar extent and differ from the cells which readily sediment as E rosettes: these respond stronger to PHA. The \"null\" fraction may contain stem cells common for both T and B lineages.", "contents": "Surface markers and functional characteristics of human blood lymphocytes residing in the operational \"null\" subset. After removal of nylon wool-adherent B and E rosetting T cells from the human blood lymphocyte population, a small fraction remains, often denoted as \"null\" subset. This fraction contains lymphocytes which are highly efficient in antibody-dependent and non-selective lymphocyte cytotoxicity. These cells possess markers. About half of them carry Fc receptors, and the majority has low avidity E and C3 receptors. Removal of low avidity E receptor-carrying cells did not abolish cytotoxicity to K-562 cells. The majority of cells carry receptors for Epstein-Barr virus but cannot be infected. The cells in mixed lymphocyte culture have a low reactivity. They aare stimulated by PHA and ConA to a similar extent and differ from the cells which readily sediment as E rosettes: these respond stronger to PHA. The \"null\" fraction may contain stem cells common for both T and B lineages."}
{"id": "PMID:231549", "title": "Cancer, viruses and environmental factors.", "content": "The genesis of Burkitt's lymphoma is visualized as proceeding in three steps: I. Primary EBV infection affects the young child, probably at a relatively high multiplicity. It immortalizes a certain number of B-lymphocytes in vivo. II. This is followed by the impact of an environmental promoting agent, perhaps chronic holoendemic malaria, providing a chronic stimulus to the proliferation of the EBV-carrying preneoplastic cells. III. Chromosomally abnormal variants appear in the stimulated tissue by chance. After certain types of changes, particularly the 8 to 14 translocation that leads to the 14q+ marker, the affected B lymphocyte would no longer obey the negative feedback controls that would otherwise restrict its proliferation in vivo.", "contents": "Cancer, viruses and environmental factors. The genesis of Burkitt's lymphoma is visualized as proceeding in three steps: I. Primary EBV infection affects the young child, probably at a relatively high multiplicity. It immortalizes a certain number of B-lymphocytes in vivo. II. This is followed by the impact of an environmental promoting agent, perhaps chronic holoendemic malaria, providing a chronic stimulus to the proliferation of the EBV-carrying preneoplastic cells. III. Chromosomally abnormal variants appear in the stimulated tissue by chance. After certain types of changes, particularly the 8 to 14 translocation that leads to the 14q+ marker, the affected B lymphocyte would no longer obey the negative feedback controls that would otherwise restrict its proliferation in vivo."}
{"id": "PMID:231553", "title": "[Hypothalamo-pituitary-adrenocortical (HPA) function in the morphine dependent rat (author's transl)].", "content": "Morphine dependence was induced by ten daily administrations of morphine with gradually increasing dosage (40--160 mg/kg/day s.c.) to male Sprague-Dawley rats, the dosage being divided in 2/day for the first 8 days and 4/day for the last 2 days. Diurnal variation in body weight in morphine dependent rats was the same as in naive rats. Although body temperature in the naive rats showed a diurnal variation with the highest at 3:00 and the lowest at 15:00, in the morphine dependent rats there was no distinct variation. Plasma corticosterone level (PC) in naive rats showed diurnal variation with the peak at 21:00 and the trough at 9:00. PC in morphine dependent rats showed the same diurnal variation as did the naive rats, while such disappeared following pentobarbital anesthesia (80 mg/kg i.p. for 45 min) and PC was low all during the day. The PC increase following formalin administration to morphine dependent rats was higher than in naive rats. 0.1 mg/kg s.c. of dexamethasone completely inhibited PC increase after formalin in naive rats, but the dexamethasone inhibition in morphine dependent rats was not complete even with a larger dose, i.e. 10 mg/kg s.c. Diurnal variations and other differences were not detected in the adrenal response to ACTH (in vivo, in vitro) between naive and morphine dpendent rats. These results suggest that HPA function takes part in the development of morphine dependence.", "contents": "[Hypothalamo-pituitary-adrenocortical (HPA) function in the morphine dependent rat (author's transl)]. Morphine dependence was induced by ten daily administrations of morphine with gradually increasing dosage (40--160 mg/kg/day s.c.) to male Sprague-Dawley rats, the dosage being divided in 2/day for the first 8 days and 4/day for the last 2 days. Diurnal variation in body weight in morphine dependent rats was the same as in naive rats. Although body temperature in the naive rats showed a diurnal variation with the highest at 3:00 and the lowest at 15:00, in the morphine dependent rats there was no distinct variation. Plasma corticosterone level (PC) in naive rats showed diurnal variation with the peak at 21:00 and the trough at 9:00. PC in morphine dependent rats showed the same diurnal variation as did the naive rats, while such disappeared following pentobarbital anesthesia (80 mg/kg i.p. for 45 min) and PC was low all during the day. The PC increase following formalin administration to morphine dependent rats was higher than in naive rats. 0.1 mg/kg s.c. of dexamethasone completely inhibited PC increase after formalin in naive rats, but the dexamethasone inhibition in morphine dependent rats was not complete even with a larger dose, i.e. 10 mg/kg s.c. Diurnal variations and other differences were not detected in the adrenal response to ACTH (in vivo, in vitro) between naive and morphine dpendent rats. These results suggest that HPA function takes part in the development of morphine dependence."}
{"id": "PMID:231554", "title": "[Thyrotropin-releasing hormone (TRH): Enhancement of dopamine dependent circling behavior and its own circling-inducing effect in unilateral striatal lesioned animals (author's transl)].", "content": "Enhancement by TRH of the dopamine(DA) agonist-induced circling behavior and effect of TRH itself on circling behavior were investigated. TRH(2.5--20 mg/kg, i.p.) remarkably enhanced the circling behavior induced by apomorphine or-L-DOPA in the mice lesioned unilaterally in the caudate nucleus by injection of 6-hydroxydopamine (60OHDA) or by tissue aspiration with subsequent reserpinization. TRH also enhanced the apomorphine-induced stereotypy in reserpinized normal mice. The above TRH-enhancing action of the circling behavior was potentiated, suppressed or unaffected by alpha-methyl-para-tyrosine (alpha-MT) or GABA-ergic drugs. In the 6-OHDA lesioned mice treated with TRH, the cyclic AMP formation by DA or apomorphine was clearly enhanced in the triatal slices taken from the lesioned side but not from the intact side. In the rats lesioned unilaterally in the nigrostriatal DA pathway by 6-OHDA, high doses of TRH injected i.p. (100 mg/kg) or into the non-lesioned caudate nucleus (50 micrograms) produced circling toward the lesioned side, which was suppressed by haloperidol or alpha-MT. TRH(10(-5)--10(-3)M) increased the 14C-DA release from the rat striatal slices in vitro. These results suggest that TRH at low doses facilitates the DA postsynaptic transmission in association with an increase of DA-stimulated cyclic AMP formation in the striatum under supersensitization of the DA receptors, and also at high doses enhances the DA neuronal activity by increasing the DA release from the striatal nerve terminals.", "contents": "[Thyrotropin-releasing hormone (TRH): Enhancement of dopamine dependent circling behavior and its own circling-inducing effect in unilateral striatal lesioned animals (author's transl)]. Enhancement by TRH of the dopamine(DA) agonist-induced circling behavior and effect of TRH itself on circling behavior were investigated. TRH(2.5--20 mg/kg, i.p.) remarkably enhanced the circling behavior induced by apomorphine or-L-DOPA in the mice lesioned unilaterally in the caudate nucleus by injection of 6-hydroxydopamine (60OHDA) or by tissue aspiration with subsequent reserpinization. TRH also enhanced the apomorphine-induced stereotypy in reserpinized normal mice. The above TRH-enhancing action of the circling behavior was potentiated, suppressed or unaffected by alpha-methyl-para-tyrosine (alpha-MT) or GABA-ergic drugs. In the 6-OHDA lesioned mice treated with TRH, the cyclic AMP formation by DA or apomorphine was clearly enhanced in the triatal slices taken from the lesioned side but not from the intact side. In the rats lesioned unilaterally in the nigrostriatal DA pathway by 6-OHDA, high doses of TRH injected i.p. (100 mg/kg) or into the non-lesioned caudate nucleus (50 micrograms) produced circling toward the lesioned side, which was suppressed by haloperidol or alpha-MT. TRH(10(-5)--10(-3)M) increased the 14C-DA release from the rat striatal slices in vitro. These results suggest that TRH at low doses facilitates the DA postsynaptic transmission in association with an increase of DA-stimulated cyclic AMP formation in the striatum under supersensitization of the DA receptors, and also at high doses enhances the DA neuronal activity by increasing the DA release from the striatal nerve terminals."}
{"id": "PMID:231556", "title": "[Treatment of orthostatic disorders of circulatory regulation by means of DET MS retard].", "content": "30 patients suffering from troubles in orthostatic circulatory regulation in the sense of a so-called hypersympathicotonic reaction were treated with DET MS retard for 4 weeks and permanently controlled concerning objective changes (circulation by modified Schellong-test on the tilting table) as well as subjective changes (symptoms). The evaluation of the findings shows the stabilisation of the regulation of blood pressure, an extensive economization of the circulatory behaviour during orthostasis, and a statistically evident improvement of clinical symptoms.", "contents": "[Treatment of orthostatic disorders of circulatory regulation by means of DET MS retard]. 30 patients suffering from troubles in orthostatic circulatory regulation in the sense of a so-called hypersympathicotonic reaction were treated with DET MS retard for 4 weeks and permanently controlled concerning objective changes (circulation by modified Schellong-test on the tilting table) as well as subjective changes (symptoms). The evaluation of the findings shows the stabilisation of the regulation of blood pressure, an extensive economization of the circulatory behaviour during orthostasis, and a statistically evident improvement of clinical symptoms."}
{"id": "PMID:231558", "title": "[Carcinoma after-care in an after-care clinic based on experiences at the Sonnenberg Clinic, Bad Soden-Allendorf].", "content": "The follow-up cure therapy in the framework of cancer follow-up treatment is of special importance. During the past 7 years 7814 patients have been treated according a special regimen in our clinic, which also includes cytostatic and hormonal therapy. Diagnostic control examinations for all patients are performed. Besides adequate medical treatment psychological and social aspects of the individual patient should be considered, furthermore the course of the disease, the question of again taking up life with their families and their partners and of returning to their former professional work. It could be shown that general discussion groups and cancer selfhelp groups, which are organized by the patients, are fruitful. It seems beneficial for the patients to participate in these activities in a follow-up clinic for a course of 6 weeks and they seem to recuperate better regarding their general health and survival time.", "contents": "[Carcinoma after-care in an after-care clinic based on experiences at the Sonnenberg Clinic, Bad Soden-Allendorf]. The follow-up cure therapy in the framework of cancer follow-up treatment is of special importance. During the past 7 years 7814 patients have been treated according a special regimen in our clinic, which also includes cytostatic and hormonal therapy. Diagnostic control examinations for all patients are performed. Besides adequate medical treatment psychological and social aspects of the individual patient should be considered, furthermore the course of the disease, the question of again taking up life with their families and their partners and of returning to their former professional work. It could be shown that general discussion groups and cancer selfhelp groups, which are organized by the patients, are fruitful. It seems beneficial for the patients to participate in these activities in a follow-up clinic for a course of 6 weeks and they seem to recuperate better regarding their general health and survival time."}
{"id": "PMID:231562", "title": "Influence of nutritional factors on the renotrophic action of ACTH in the uninephrectomized rat.", "content": "In the rat, renal compensatory hypertrophy (RCH) was apparent 48 h after uninephrectomy; it was significantly enhanced by long-acting beta1-24-corticotrophin (ACTH) when the animals had free access to food and a NaCl solution (9 g/l). In rats starved after uninephrectomy but drinking the NaCl solution freely, RCH was suppressed: the weights of the body, heart, liver, and solitary kidney were reduced. In similarly starved rats treated with ACTH, the weights of the heart and the solitary kidney were normal. RCH was also impaired in rats fed only a glucose solution (30 g/dl) after uninephrectomy, but it is restored by ACTH, which significantly increases the weight of the remaining kidney. This renotrophic action of ACTH may be related to hyperglycemia and, perhaps, elevated urinary K excretion, which occur in hyper-adrenocorticism and increase the work load of the nephron.", "contents": "Influence of nutritional factors on the renotrophic action of ACTH in the uninephrectomized rat. In the rat, renal compensatory hypertrophy (RCH) was apparent 48 h after uninephrectomy; it was significantly enhanced by long-acting beta1-24-corticotrophin (ACTH) when the animals had free access to food and a NaCl solution (9 g/l). In rats starved after uninephrectomy but drinking the NaCl solution freely, RCH was suppressed: the weights of the body, heart, liver, and solitary kidney were reduced. In similarly starved rats treated with ACTH, the weights of the heart and the solitary kidney were normal. RCH was also impaired in rats fed only a glucose solution (30 g/dl) after uninephrectomy, but it is restored by ACTH, which significantly increases the weight of the remaining kidney. This renotrophic action of ACTH may be related to hyperglycemia and, perhaps, elevated urinary K excretion, which occur in hyper-adrenocorticism and increase the work load of the nephron."}
{"id": "PMID:231566", "title": "Inhibitory control of the pituitary LH secretion by LH-RH in male rats.", "content": "Luteinizing hormone-releasing hormone (LH-RH) was administered to prepubertal male rats (intact, castrate or castrate-adrenalectomized, 60 g body weight) for 28 days (1 microgram LH-RH/day, s.c.), at a 10-fold physiological dose, as compared to the minimal FSH-releasing dose of 100 ng/rat s.c. In intact rats, serum LH and weight of androgen-dependent organs (vented prostate, seminal vesicles) were reduced after 14 days of treatment. In castrate rats, the postcastration rise in serum LH was abolished by treatment. Pituitary LH content, FSH secretion and prolactin secretion were not suppressed. Hypothalamic LH-RH was increased at 14 and 21 days. In castrate adrenalectomized male rats, LH secretion was also suppressed by 1 microgram LH-RH s.c. x 28 days. The hypothalamic LH-RH content did not increase. The pituitary LH-RH receptor level was not down-regulated after 14 days treatment either in intact or castrate male rats. Pituitary inhibition (LH release) in rats by a supraphysiological dose of LH-RH given for 28 days indicates that the optimal regime for chronic treatment has to be determined by monitoring LH release at regular intervals. Direct pituitary inhibition by LH-RH may explain some of the unexpected antifertility effects observed with high doses of LH-RH.", "contents": "Inhibitory control of the pituitary LH secretion by LH-RH in male rats. Luteinizing hormone-releasing hormone (LH-RH) was administered to prepubertal male rats (intact, castrate or castrate-adrenalectomized, 60 g body weight) for 28 days (1 microgram LH-RH/day, s.c.), at a 10-fold physiological dose, as compared to the minimal FSH-releasing dose of 100 ng/rat s.c. In intact rats, serum LH and weight of androgen-dependent organs (vented prostate, seminal vesicles) were reduced after 14 days of treatment. In castrate rats, the postcastration rise in serum LH was abolished by treatment. Pituitary LH content, FSH secretion and prolactin secretion were not suppressed. Hypothalamic LH-RH was increased at 14 and 21 days. In castrate adrenalectomized male rats, LH secretion was also suppressed by 1 microgram LH-RH s.c. x 28 days. The hypothalamic LH-RH content did not increase. The pituitary LH-RH receptor level was not down-regulated after 14 days treatment either in intact or castrate male rats. Pituitary inhibition (LH release) in rats by a supraphysiological dose of LH-RH given for 28 days indicates that the optimal regime for chronic treatment has to be determined by monitoring LH release at regular intervals. Direct pituitary inhibition by LH-RH may explain some of the unexpected antifertility effects observed with high doses of LH-RH."}
{"id": "PMID:231567", "title": "The use of artificial beta cell in diagnosis and treatment of insulinoma.", "content": "The glucose-controlled insulin infusion system (GCIIS), the socalled artificial beta-cell, is an important and useful device for detecting and treating hypoglycemic reactions. The dangers of several diagnostic tests such as the tolbutamide or the insulin response test may successfully be avoided. Patients suffering from severe hypoglycemia are kept in normoglycemia by the feedback-controlled dextrose infusion before and during operation.", "contents": "The use of artificial beta cell in diagnosis and treatment of insulinoma. The glucose-controlled insulin infusion system (GCIIS), the socalled artificial beta-cell, is an important and useful device for detecting and treating hypoglycemic reactions. The dangers of several diagnostic tests such as the tolbutamide or the insulin response test may successfully be avoided. Patients suffering from severe hypoglycemia are kept in normoglycemia by the feedback-controlled dextrose infusion before and during operation."}
{"id": "PMID:231568", "title": "Artificial beta-cell application in two cases of insulinoma: a different pattern in beta-cell adenoma and carcinoma.", "content": "With the aid of an artificial beta-cell (Biostator, Miles Laboratories Inc.), a different metabolic and biological pattern of behaviour was observed in benign versus malignant insulinoma. In the patient with beta-cell adenoma but not in the one with carcinoma, plasma insulin concentrations decreased promptly and markedly, and blood glucose increased during diazoxide and somatostatin infusion. Moreover, only in the adenoma patient was glucose need characterized by a circadian rhythm with the maximum values during daytime. This behavior could reflect the degree of tumor beta-cell differentiation. The controlled glucose and insulin infusion was of great help during and after surgical treatment.", "contents": "Artificial beta-cell application in two cases of insulinoma: a different pattern in beta-cell adenoma and carcinoma. With the aid of an artificial beta-cell (Biostator, Miles Laboratories Inc.), a different metabolic and biological pattern of behaviour was observed in benign versus malignant insulinoma. In the patient with beta-cell adenoma but not in the one with carcinoma, plasma insulin concentrations decreased promptly and markedly, and blood glucose increased during diazoxide and somatostatin infusion. Moreover, only in the adenoma patient was glucose need characterized by a circadian rhythm with the maximum values during daytime. This behavior could reflect the degree of tumor beta-cell differentiation. The controlled glucose and insulin infusion was of great help during and after surgical treatment."}
{"id": "PMID:231569", "title": "Inhibition of murine sarcoma virus induced transformation in an adenovirus -- NRK system.", "content": "Cell transformation induced by murine sarcoma virus (MSV-M) is significantly inhibited (80--90%) in a clonal line of normal rat kidney (NRK) cells when they are infected with rat cell passaged adenovirus 12 (R-Ad12). No inhibition is seen when R-Ad12 is added simultaneously with, or 1 1/2 or 24 hr after, MSV-M infection, suggesting that inhibition occurs most probably intracellularly. There is also a direct correlation between the extent of focus formation and the concentration of R-Ad12 used. Concentrations of R-Ad12 used to inhibit cell transformation do not affect cell growth. Significant inhibition in foci (90--100%) is also evident in the first two subcultures of R-Ad12 infected NRK cells. The mechanism of the inhibition is not yet known.", "contents": "Inhibition of murine sarcoma virus induced transformation in an adenovirus -- NRK system. Cell transformation induced by murine sarcoma virus (MSV-M) is significantly inhibited (80--90%) in a clonal line of normal rat kidney (NRK) cells when they are infected with rat cell passaged adenovirus 12 (R-Ad12). No inhibition is seen when R-Ad12 is added simultaneously with, or 1 1/2 or 24 hr after, MSV-M infection, suggesting that inhibition occurs most probably intracellularly. There is also a direct correlation between the extent of focus formation and the concentration of R-Ad12 used. Concentrations of R-Ad12 used to inhibit cell transformation do not affect cell growth. Significant inhibition in foci (90--100%) is also evident in the first two subcultures of R-Ad12 infected NRK cells. The mechanism of the inhibition is not yet known."}
{"id": "PMID:231570", "title": "Isolation of alveolar type II cells by centrifugal elutriation.", "content": "Centrifugal elutriation (counterflow centrifugation) was used to develop a reproducible method for obtaining a nearly pure population of isolated alveolar type II cells. Lung was dissociated into individual cells with recrystallized trypsin, and the type II cells were partially purified by centrifugation on a discontinuous density gradient. The alveolar type II cells were finally purified by centrifugal elutriation. Cells were collected from the elutriator rotor by stepwise increases in flow rates. Cells obtained at flow rates of 7 and 14 ml per min were lymphocytes, other small cells, a few type II cells and cell debris; cells collected at flow rates of 18 and 22 ml per min were mainly type II cells; and cells collected at flow rates of 28, 34 and 43 ml per min were macrophages, some type II cells, other lung cells and cell aggregates. At flow rates of 18 and 22 ml per min, 1.9 +/- 1.0 x 10(6) cells per rat lung (mean +/- S.D., n=30) were recovered of which 86 +/- 6% were type II cells. At these flow rates, 94% of the cells excluded the vital dye erythrosin B from their cytoplasm. They consumed oxygen at a rate of 101 +/- 21 nmol per hr . 10(6) cells (mean +/- S.D., n=4), and their oxygen consumption increased only 10% after 10 mM sodium succinate was added. The cells incorporated [14C]leucine into protein and lipid for 4 hr. Electron micrographs of the cells collected at flow rates of 18 and 22 ml per min show a high percentage of morphologically intact alveolar type II cells. We conclude that centrifugral elutriation is a reproducible method for obtaining nearly pure, metabolically active alveolar type II cells.", "contents": "Isolation of alveolar type II cells by centrifugal elutriation. Centrifugal elutriation (counterflow centrifugation) was used to develop a reproducible method for obtaining a nearly pure population of isolated alveolar type II cells. Lung was dissociated into individual cells with recrystallized trypsin, and the type II cells were partially purified by centrifugation on a discontinuous density gradient. The alveolar type II cells were finally purified by centrifugal elutriation. Cells were collected from the elutriator rotor by stepwise increases in flow rates. Cells obtained at flow rates of 7 and 14 ml per min were lymphocytes, other small cells, a few type II cells and cell debris; cells collected at flow rates of 18 and 22 ml per min were mainly type II cells; and cells collected at flow rates of 28, 34 and 43 ml per min were macrophages, some type II cells, other lung cells and cell aggregates. At flow rates of 18 and 22 ml per min, 1.9 +/- 1.0 x 10(6) cells per rat lung (mean +/- S.D., n=30) were recovered of which 86 +/- 6% were type II cells. At these flow rates, 94% of the cells excluded the vital dye erythrosin B from their cytoplasm. They consumed oxygen at a rate of 101 +/- 21 nmol per hr . 10(6) cells (mean +/- S.D., n=4), and their oxygen consumption increased only 10% after 10 mM sodium succinate was added. The cells incorporated [14C]leucine into protein and lipid for 4 hr. Electron micrographs of the cells collected at flow rates of 18 and 22 ml per min show a high percentage of morphologically intact alveolar type II cells. We conclude that centrifugral elutriation is a reproducible method for obtaining nearly pure, metabolically active alveolar type II cells."}
{"id": "PMID:231571", "title": "Inhibition of cellular transition from G1-resting to G1-prereplicative phase by aminonucleoside of puromycin.", "content": "Human embryonic lung fibroblasts (IMR-90 and WI-38) were arrested in the G1 phase of the cell cycle by serum deprivation and high population density. Within 1 hr after the addition of medium containing fresh serum, these cells showed an increase in rRNA synthesis. The inclusion of 100 micrograms per ml aminonucleoside of puromycin (AMS) in the fresh medium eliminated the serum stimulation of rRNA synthesis and prevented the cells from making the G1-resting phase to G1-prereplicative phase transition. AMS also prevented the synthesis of HnRNA normally found within 10 hr after serum stimulation. Serum-stimulated RNA synthesis in starved, SV-40 transformed fibroblasts (WI-38-VA-13 cells) was inhibited, but not completely prevented, by AMS indicating that transformed cells may produce specific RNA's that are not AMS-sensitive and that may be responsible for the failure of transformed cells to be arrested in G1.", "contents": "Inhibition of cellular transition from G1-resting to G1-prereplicative phase by aminonucleoside of puromycin. Human embryonic lung fibroblasts (IMR-90 and WI-38) were arrested in the G1 phase of the cell cycle by serum deprivation and high population density. Within 1 hr after the addition of medium containing fresh serum, these cells showed an increase in rRNA synthesis. The inclusion of 100 micrograms per ml aminonucleoside of puromycin (AMS) in the fresh medium eliminated the serum stimulation of rRNA synthesis and prevented the cells from making the G1-resting phase to G1-prereplicative phase transition. AMS also prevented the synthesis of HnRNA normally found within 10 hr after serum stimulation. Serum-stimulated RNA synthesis in starved, SV-40 transformed fibroblasts (WI-38-VA-13 cells) was inhibited, but not completely prevented, by AMS indicating that transformed cells may produce specific RNA's that are not AMS-sensitive and that may be responsible for the failure of transformed cells to be arrested in G1."}
{"id": "PMID:231577", "title": "High-density lipoprotein cholesterol concentration and other serum lipids in an isolated island community free of coronary heart disease.", "content": "Fasting serum high-density lipoprotein (HDL) cholesterol, other lipid concentrations and related characteristics have been measured in 87% of 261 residents aged over 5 years on the small isolated island of Salt Cay, Turks and Caicos Isles. Only one subject, a hypertensive woman, had a major electrocardiographic Q wave abnormality, and none of the islanders had clinical coronary heart disease. These findings, together with local clinical experience indicated a low incidence of coronary heart disease in this community. Adult mean concentrations of HDL cholesterol (1.6 mmol/l) and serum total triglyceride (0.81 mmol/l) were relatively high and low respectively compared with those of men and women in North American communities. Unlike findings in North America, there was no significant sex difference in HDL cholesterol concentration apparent in adulthood and this was not explained by sex differences in alcohol consumption (positively correlated with HDL cholesterol in both sexes) or adiposity (negatively correlated with HDL cholesterol in men only). Residents who were recovering from an epidemic of mild upper respiratory infection had on average a 9% reduction in HDL cholesterol concentration compared with the remainder of the community. The lipoprotein lipid pattern in these people is consistent with a low cardiovascular risk status, and might account for the apparent absence of coronary heart disease on the island.", "contents": "High-density lipoprotein cholesterol concentration and other serum lipids in an isolated island community free of coronary heart disease. Fasting serum high-density lipoprotein (HDL) cholesterol, other lipid concentrations and related characteristics have been measured in 87% of 261 residents aged over 5 years on the small isolated island of Salt Cay, Turks and Caicos Isles. Only one subject, a hypertensive woman, had a major electrocardiographic Q wave abnormality, and none of the islanders had clinical coronary heart disease. These findings, together with local clinical experience indicated a low incidence of coronary heart disease in this community. Adult mean concentrations of HDL cholesterol (1.6 mmol/l) and serum total triglyceride (0.81 mmol/l) were relatively high and low respectively compared with those of men and women in North American communities. Unlike findings in North America, there was no significant sex difference in HDL cholesterol concentration apparent in adulthood and this was not explained by sex differences in alcohol consumption (positively correlated with HDL cholesterol in both sexes) or adiposity (negatively correlated with HDL cholesterol in men only). Residents who were recovering from an epidemic of mild upper respiratory infection had on average a 9% reduction in HDL cholesterol concentration compared with the remainder of the community. The lipoprotein lipid pattern in these people is consistent with a low cardiovascular risk status, and might account for the apparent absence of coronary heart disease on the island."}
{"id": "PMID:231578", "title": "Transition of nervous activity from signals to information processing.", "content": "The author starts from the fact that although the signals are the information bearers, they cannot be identified with the information they are carrying. Therefore, in order to achieve control as adequate as possible of human behaviour, the nervous system has to discover the information brought by different signals. The activity of information discovery is realized by means of superisation process, that is by means of transition from many lower order signals to a superior order signal. By means of the superisation process a gradual recognition of the respective signals emitting sources is realised. This recognition is made with the help of certain logical circuits representing the models of different sources written in the structure of the neuronal network. In this manner the nervous system passes step by step from control by means of signals to control by means of information by which the superior structures thereby exert much more subtle control, and supervise the inferior structures working by signals. But, because this control cannot remove all the errors of the inferior structures, different psychical and psychosomatic illnesses can occur.", "contents": "Transition of nervous activity from signals to information processing. The author starts from the fact that although the signals are the information bearers, they cannot be identified with the information they are carrying. Therefore, in order to achieve control as adequate as possible of human behaviour, the nervous system has to discover the information brought by different signals. The activity of information discovery is realized by means of superisation process, that is by means of transition from many lower order signals to a superior order signal. By means of the superisation process a gradual recognition of the respective signals emitting sources is realised. This recognition is made with the help of certain logical circuits representing the models of different sources written in the structure of the neuronal network. In this manner the nervous system passes step by step from control by means of signals to control by means of information by which the superior structures thereby exert much more subtle control, and supervise the inferior structures working by signals. But, because this control cannot remove all the errors of the inferior structures, different psychical and psychosomatic illnesses can occur."}
{"id": "PMID:231579", "title": "Effects of interstimulus interval on latency of the brainstem auditory evoked potential.", "content": "Peak latency of the inferior collicular response (wave V) of the brainstem auditory evoked potential (BAEP) increases with decreasing interstimulus interval (ISI). The present research investigated relative peak shifts of major components of the BAEP in an attempt to identify the source of the observed shift in wave V. Peripheral as well as central transmission times (CTT) were computed for 9 young adults between an ISI of 100 msec and an ISI of 10 msec. The results indicate that shifts in wave V latency with changing ISI are due to a combination of central and peripheral processes. The magnitude of the shift observed for wave V was approximately 0.50 msec. This increase in latency was accounted for by an average 0.29 msec increase in peripheral transmission time, a 0.14 msec increase in CTT between waves I and III, and a 0.07 msec increase in CTT between waves III and V. The results suggest a dual process underlying latency changes in wave V of the BAEP as a function of decreasing ISI. These are peripheral adaptation or fatigue and central processes that may include short-term habituation.", "contents": "Effects of interstimulus interval on latency of the brainstem auditory evoked potential. Peak latency of the inferior collicular response (wave V) of the brainstem auditory evoked potential (BAEP) increases with decreasing interstimulus interval (ISI). The present research investigated relative peak shifts of major components of the BAEP in an attempt to identify the source of the observed shift in wave V. Peripheral as well as central transmission times (CTT) were computed for 9 young adults between an ISI of 100 msec and an ISI of 10 msec. The results indicate that shifts in wave V latency with changing ISI are due to a combination of central and peripheral processes. The magnitude of the shift observed for wave V was approximately 0.50 msec. This increase in latency was accounted for by an average 0.29 msec increase in peripheral transmission time, a 0.14 msec increase in CTT between waves I and III, and a 0.07 msec increase in CTT between waves III and V. The results suggest a dual process underlying latency changes in wave V of the BAEP as a function of decreasing ISI. These are peripheral adaptation or fatigue and central processes that may include short-term habituation."}
{"id": "PMID:231582", "title": "Effect of diethylstilbestrol on replication and transformation by human herpesviruses.", "content": "Human embryo fibroblasts treated with diethylstilbestrol (DES) gave rise to slightly increased plaque production by cytomegalovirus (CMV): plaques were also slightly larger in treated cells when compared to those in untreated cultures. There was no significant enhancement of plaque production by herpes simplex virus (HSV) types 1 and 2 in the human cells or in primary rabbit kidney cells treated with DES. Growth analyses of HSV and CMV in DES-treated cells failed to reveal enhancement of virus production when compared to untreated cells. The frequency of biochemical transformation of mouse cells deficient in thymidine kinase (TK) to the TK+ phenotype by HSV was markedly enhanced when cells were pretreated with DES. TK+-transformed colonies arising from DES-treated cells were also larger than those derived from untreated cultures. These reveal that DES increases susceptibility of human cell lines to CMV infection and enhances efficiency of biochemical transformation of mouse cells by HSV.", "contents": "Effect of diethylstilbestrol on replication and transformation by human herpesviruses. Human embryo fibroblasts treated with diethylstilbestrol (DES) gave rise to slightly increased plaque production by cytomegalovirus (CMV): plaques were also slightly larger in treated cells when compared to those in untreated cultures. There was no significant enhancement of plaque production by herpes simplex virus (HSV) types 1 and 2 in the human cells or in primary rabbit kidney cells treated with DES. Growth analyses of HSV and CMV in DES-treated cells failed to reveal enhancement of virus production when compared to untreated cells. The frequency of biochemical transformation of mouse cells deficient in thymidine kinase (TK) to the TK+ phenotype by HSV was markedly enhanced when cells were pretreated with DES. TK+-transformed colonies arising from DES-treated cells were also larger than those derived from untreated cultures. These reveal that DES increases susceptibility of human cell lines to CMV infection and enhances efficiency of biochemical transformation of mouse cells by HSV."}
{"id": "PMID:231583", "title": "Cervical cancer cell lines containing herpesvirus markers.", "content": "Five epithelioid cell lines were established from invasive cervical carcinoma tissue and were examined for herpes simplex virus (HSV) antigens or virus-induced changes. Immunofluorescence studies with antiserum to an HSV type 2 nonstructural polypeptide detected perinuclear antigens. In these cell lines, concentrations of a membrane fucopeptide that is regularly present in normal cells were reduced to levels similar to those previously observed in virus-transformed cells. One of the cell lines inoculated into athymic mice produced tumors.", "contents": "Cervical cancer cell lines containing herpesvirus markers. Five epithelioid cell lines were established from invasive cervical carcinoma tissue and were examined for herpes simplex virus (HSV) antigens or virus-induced changes. Immunofluorescence studies with antiserum to an HSV type 2 nonstructural polypeptide detected perinuclear antigens. In these cell lines, concentrations of a membrane fucopeptide that is regularly present in normal cells were reduced to levels similar to those previously observed in virus-transformed cells. One of the cell lines inoculated into athymic mice produced tumors."}
{"id": "PMID:231584", "title": "Effect of antipain on radiation induction of endogenous type-C virus from mouse cells in vitro.", "content": "Xenotropic murine type-C virus was induced after X-ray or UV light irradiation of K-Balb cells. The induction was markedly suppressed by postirradiation treatment of the cells with antipain, a protease inhibitor of microbial origin. Virus expression was unaffected when the cells were treated with halogenated pyrimidines.", "contents": "Effect of antipain on radiation induction of endogenous type-C virus from mouse cells in vitro. Xenotropic murine type-C virus was induced after X-ray or UV light irradiation of K-Balb cells. The induction was markedly suppressed by postirradiation treatment of the cells with antipain, a protease inhibitor of microbial origin. Virus expression was unaffected when the cells were treated with halogenated pyrimidines."}
{"id": "PMID:231581", "title": "Chemodectomas: a review of 17 cases.", "content": "Seventeen cases of chemodectomas seen in the University College Hospital, Ibadan, are presented. Eight of them (48%) are carotid body tumors, while six (36%) are glomus jugulare. The rest are subglottic, abdominal and multicentric. The sex distribution for the two major types is equal for males and females; but they all seem to appear in younger age groups. Operative mortality has been exclusive to carotid body tumors (50% for this group), while bleeding is the leading postoperative complication in all the cases. The embryology, pathophysiology and clinical presentation of chemodectomas are discussed and it is suggested that, in the management of this condition, the advantages of operation should be weighed against morbidity and mortality risks.", "contents": "Chemodectomas: a review of 17 cases. Seventeen cases of chemodectomas seen in the University College Hospital, Ibadan, are presented. Eight of them (48%) are carotid body tumors, while six (36%) are glomus jugulare. The rest are subglottic, abdominal and multicentric. The sex distribution for the two major types is equal for males and females; but they all seem to appear in younger age groups. Operative mortality has been exclusive to carotid body tumors (50% for this group), while bleeding is the leading postoperative complication in all the cases. The embryology, pathophysiology and clinical presentation of chemodectomas are discussed and it is suggested that, in the management of this condition, the advantages of operation should be weighed against morbidity and mortality risks."}
{"id": "PMID:231585", "title": "Foot-and-mouth disease virus immunogenic capsid protein VPT: N-terminal sequences and immunogenic peptides obtained by CNBr and tryptic cleavages.", "content": "The immunogenic capsid protein (VPT), circa 30 kiladaltons (kd), of foot-and-mouth disease virus was examined for (i) its ability to induce neutralizing antibody in guinea pigs after chemical modifications and CNBr or tryptic cleavages and (ii) N-terminal amino sequence homology across three virus types. The immunogenicity of VPT was inactivated by glutaraldehyde treatment, carboxymethylation and maleylation or citraconylation. However, de-citraconylation restored part of the lost activity. Cleavage of type A12 VPT with CNBr produced an immunogenic peptide of circa 13 kd. A slightly larger (ca. 16 kd) immunogenic doublet, VPTab, was obtained by tyrptic cleavage of VPT in the virion. Sequence homologies of circa 85% were found between the first 26 amino acids at the N-terminus of VP chains from virus types A12 strain 119 (A12), C3 Resende (C3R) and O1 Brugge (O1B).", "contents": "Foot-and-mouth disease virus immunogenic capsid protein VPT: N-terminal sequences and immunogenic peptides obtained by CNBr and tryptic cleavages. The immunogenic capsid protein (VPT), circa 30 kiladaltons (kd), of foot-and-mouth disease virus was examined for (i) its ability to induce neutralizing antibody in guinea pigs after chemical modifications and CNBr or tryptic cleavages and (ii) N-terminal amino sequence homology across three virus types. The immunogenicity of VPT was inactivated by glutaraldehyde treatment, carboxymethylation and maleylation or citraconylation. However, de-citraconylation restored part of the lost activity. Cleavage of type A12 VPT with CNBr produced an immunogenic peptide of circa 13 kd. A slightly larger (ca. 16 kd) immunogenic doublet, VPTab, was obtained by tyrptic cleavage of VPT in the virion. Sequence homologies of circa 85% were found between the first 26 amino acids at the N-terminus of VP chains from virus types A12 strain 119 (A12), C3 Resende (C3R) and O1 Brugge (O1B)."}
{"id": "PMID:231586", "title": "Comparative study of herpes group virus-induced DNA polymerases.", "content": "A comparative biochemical study of virus-induced DNA polymerases was made among the herpes group viruses: namely, herpes simplex virus (HSV) type 1 and type 2, human cytomegalovirus (HCMV) and varicella-zoster virus (VZV). Although these virus-induced enzymes shared some biochemical properties, they differed in several important aspects. All these virus-induced DNA polymerases could efficiently use poly(dC) . oligo(dG)12--18 and poly(dA) . oligo(dT)12--18 as template-primers. However, in phosphocellulose chromatography, HSV-1- and HSV-2-induced enzymes were eluted at the low concentration of 0.18--0.20 M NaCl and the counterparts of HCMV and VZV were eluted at 0.30--0.32 M. The former two enzymes were more sensitive to lower concentrations of phosphonoacetate and ethyl phosphonoacetate than the latter two enzymes. Moreover, the activity of HSV-1- and HSV-2-specified DNA polymerases was 5 times greater in the presence of 60 mM ammonium sulfate if poly(dA) . oligo(dT)12--18 was used as template-primer, while HCMV- and VZV-induced enzyme activities were only about twice as great under the same conditions. Futhermore, DNase activity was conspicuous in both HSV-1- and HSV-2-infected WI-38 cells, but was not detectable in HCMV- and VZV-infected cells. After storage for 1 year at 4 degrees, the HSV-1-induced DNA polymerase was the most thermostable of the four viral enzymes.", "contents": "Comparative study of herpes group virus-induced DNA polymerases. A comparative biochemical study of virus-induced DNA polymerases was made among the herpes group viruses: namely, herpes simplex virus (HSV) type 1 and type 2, human cytomegalovirus (HCMV) and varicella-zoster virus (VZV). Although these virus-induced enzymes shared some biochemical properties, they differed in several important aspects. All these virus-induced DNA polymerases could efficiently use poly(dC) . oligo(dG)12--18 and poly(dA) . oligo(dT)12--18 as template-primers. However, in phosphocellulose chromatography, HSV-1- and HSV-2-induced enzymes were eluted at the low concentration of 0.18--0.20 M NaCl and the counterparts of HCMV and VZV were eluted at 0.30--0.32 M. The former two enzymes were more sensitive to lower concentrations of phosphonoacetate and ethyl phosphonoacetate than the latter two enzymes. Moreover, the activity of HSV-1- and HSV-2-specified DNA polymerases was 5 times greater in the presence of 60 mM ammonium sulfate if poly(dA) . oligo(dT)12--18 was used as template-primer, while HCMV- and VZV-induced enzyme activities were only about twice as great under the same conditions. Futhermore, DNase activity was conspicuous in both HSV-1- and HSV-2-infected WI-38 cells, but was not detectable in HCMV- and VZV-infected cells. After storage for 1 year at 4 degrees, the HSV-1-induced DNA polymerase was the most thermostable of the four viral enzymes."}
{"id": "PMID:231587", "title": "Cytomegalovirus isolations from cell cultures of human adenocarcinomas of the colon.", "content": "Cytomegalovirus was isolated from cell cultures derived from 3 of 16 surgical specimens of adenocarcinomas of the colon. Virus identification was accomplished through electron microscopical, cytochemical, and immunofluorescent procedures.", "contents": "Cytomegalovirus isolations from cell cultures of human adenocarcinomas of the colon. Cytomegalovirus was isolated from cell cultures derived from 3 of 16 surgical specimens of adenocarcinomas of the colon. Virus identification was accomplished through electron microscopical, cytochemical, and immunofluorescent procedures."}
{"id": "PMID:231588", "title": "Subculture requirement for rescue of SV40 from 'nonrescuable' cell lines.", "content": "Virus could be rescued by cell fusion techniques from the H50, BRKSV (Bam I linear), 14B and 14B (1--4) cell lines, which contain the entire SV40 genome but have previously yielded negative results by this method. Virus could not be rescued from the T22 cell line, which was transformed by defective virus. The T-antigen-negative flat revertant cell line, 14B (1--4), converted to T-antigen-positive prior to rescue. Subculture and extensive monitoring for production of infectious virus appeared to be prerequisite for detecting virus rescue.", "contents": "Subculture requirement for rescue of SV40 from 'nonrescuable' cell lines. Virus could be rescued by cell fusion techniques from the H50, BRKSV (Bam I linear), 14B and 14B (1--4) cell lines, which contain the entire SV40 genome but have previously yielded negative results by this method. Virus could not be rescued from the T22 cell line, which was transformed by defective virus. The T-antigen-negative flat revertant cell line, 14B (1--4), converted to T-antigen-positive prior to rescue. Subculture and extensive monitoring for production of infectious virus appeared to be prerequisite for detecting virus rescue."}
{"id": "PMID:231590", "title": "[Epidermolysis bullosa dystrophica inversa, a review and case report].", "content": "An additional case of epidermolysis bullosa dystrophica inversa is reported. A review of the literature shows that until now reports about probably 15 patients from seven families were published, although the first 13 patients were not investigated by electron microscope [3]. By blistering beneath the basal lamina similar to the Hallopeau-Siemens type these patients develop bullae predominantly at the trunk and the inverse sites of the axillar and genitoanal regions continuously or at close intervals starting shortly after birth. The mucous membranes of the mouth, the esophagus, and the cornea and conjunctiva of the eye are very often involved. By bacterial infection of the skin lesions the patients develop hpochrome anemia. The web-like structures in the esophagus following blistering can be successfully treated by careful dilatation because of the low tendency to scar formation. An autosomal recessive mode of inheritance seems to be most likely.", "contents": "[Epidermolysis bullosa dystrophica inversa, a review and case report]. An additional case of epidermolysis bullosa dystrophica inversa is reported. A review of the literature shows that until now reports about probably 15 patients from seven families were published, although the first 13 patients were not investigated by electron microscope [3]. By blistering beneath the basal lamina similar to the Hallopeau-Siemens type these patients develop bullae predominantly at the trunk and the inverse sites of the axillar and genitoanal regions continuously or at close intervals starting shortly after birth. The mucous membranes of the mouth, the esophagus, and the cornea and conjunctiva of the eye are very often involved. By bacterial infection of the skin lesions the patients develop hpochrome anemia. The web-like structures in the esophagus following blistering can be successfully treated by careful dilatation because of the low tendency to scar formation. An autosomal recessive mode of inheritance seems to be most likely."}
{"id": "PMID:231600", "title": "Adrenocortical function in rats chronically exposed to high altitude.", "content": "In rats exposed to a simulated altitude of 5,486 m for 3 mo, pituitary and adrenal glands hypertrophied and plasma levels of corticosterone increased more than threefold over sea-level controls. The in vitro rates of corticosterone production by the quartered adrenal gland were significantly enhanced, but the responsiveness of the adrenal gland to ACTH remained normal.", "contents": "Adrenocortical function in rats chronically exposed to high altitude. In rats exposed to a simulated altitude of 5,486 m for 3 mo, pituitary and adrenal glands hypertrophied and plasma levels of corticosterone increased more than threefold over sea-level controls. The in vitro rates of corticosterone production by the quartered adrenal gland were significantly enhanced, but the responsiveness of the adrenal gland to ACTH remained normal."}
{"id": "PMID:231601", "title": "Effects of hypophysectomy and dexamethasone on rat adrenal response to microwaves.", "content": "Circulating corticosterone levels were measured to compare the adrenocortical response to acute microwave exposure of normal, hypophysectomized, or sham-hypophysectomized rats. Plasma corticosterone levels in acutely hypophysectomized rats exposed to 60 mW/cm2 for 60 min were below control levels, indicating that the microwave-induced corticosterone response observed in normal, intact rats is dependent on ACTH secretion by the pituitary. In other groups of rats pretreated with dexamethasone before being exposed to microwaves for 60 min, the corticosterone response to a 50-mW/cm2 exposure was completely suppressed by doses equal to or greater than 3.2 micrograms dexamethasone/100 g body weight. However, the corticosterone response to a 70-mW/cm2 exposure was only partially suppressed by prior administration of 3.2 or 5.6 micrograms dexamethasone/100 g BW. The evidence obtained in these experiments, in conjunction with the results of other experiments previously reported, is consistent with the hypothesis that the stimulation of the adrenal axis in the microwave-exposed rat is a systemic, integrative process due to a general hyperthermia.", "contents": "Effects of hypophysectomy and dexamethasone on rat adrenal response to microwaves. Circulating corticosterone levels were measured to compare the adrenocortical response to acute microwave exposure of normal, hypophysectomized, or sham-hypophysectomized rats. Plasma corticosterone levels in acutely hypophysectomized rats exposed to 60 mW/cm2 for 60 min were below control levels, indicating that the microwave-induced corticosterone response observed in normal, intact rats is dependent on ACTH secretion by the pituitary. In other groups of rats pretreated with dexamethasone before being exposed to microwaves for 60 min, the corticosterone response to a 50-mW/cm2 exposure was completely suppressed by doses equal to or greater than 3.2 micrograms dexamethasone/100 g body weight. However, the corticosterone response to a 70-mW/cm2 exposure was only partially suppressed by prior administration of 3.2 or 5.6 micrograms dexamethasone/100 g BW. The evidence obtained in these experiments, in conjunction with the results of other experiments previously reported, is consistent with the hypothesis that the stimulation of the adrenal axis in the microwave-exposed rat is a systemic, integrative process due to a general hyperthermia."}
{"id": "PMID:231602", "title": "Ventilatory responses to CO2 and lung inflation in tonic versus phasic REM sleep.", "content": "Ventilatory responses to CO2 and to lung inflation were compared in four dogs during tonic and phasic segments of rapid-eye-movement (REM) sleep. Phasic REM sleep (P-REM) was identified by the presence of bursts of rapid eye movements, visible muscle twitchings, and frequent phasic discharges in the nuchal electromyogram. These features were absent during tonic REM sleep (T-REM). During P-REM the response of minute volume of ventilation (VI) to progressive hypercapnia (0.58 +/- 0.19 (l/min)/Torr, mean +/- SE) was significantly less than in slow-wave sleep (SWS) (1.40 +/- 0.14; P less than 0.05). In contrast, during T-REM the response (1.48 +/- 0.19) was similar to that in SWS. Similarly, during P-REM the duration of apnea (5.9 +/- 1.5 s) elicited by sustained inflation of the lungs with 1.0 liter of air, was significantly shorter than in SWS (25.8 +/- 0.8); in contrast, during T-REM the duration of apnea (17.8 +/- 3.6) was similar to that in SWS. The results indicate that previously described decreases in VI responses to CO2 and apneic responses to lung inflation during P-REM, compared to SWS, are related to the phasic phenomena of REM sleep, rather than to the REM sleep state per se.", "contents": "Ventilatory responses to CO2 and lung inflation in tonic versus phasic REM sleep. Ventilatory responses to CO2 and to lung inflation were compared in four dogs during tonic and phasic segments of rapid-eye-movement (REM) sleep. Phasic REM sleep (P-REM) was identified by the presence of bursts of rapid eye movements, visible muscle twitchings, and frequent phasic discharges in the nuchal electromyogram. These features were absent during tonic REM sleep (T-REM). During P-REM the response of minute volume of ventilation (VI) to progressive hypercapnia (0.58 +/- 0.19 (l/min)/Torr, mean +/- SE) was significantly less than in slow-wave sleep (SWS) (1.40 +/- 0.14; P less than 0.05). In contrast, during T-REM the response (1.48 +/- 0.19) was similar to that in SWS. Similarly, during P-REM the duration of apnea (5.9 +/- 1.5 s) elicited by sustained inflation of the lungs with 1.0 liter of air, was significantly shorter than in SWS (25.8 +/- 0.8); in contrast, during T-REM the duration of apnea (17.8 +/- 3.6) was similar to that in SWS. The results indicate that previously described decreases in VI responses to CO2 and apneic responses to lung inflation during P-REM, compared to SWS, are related to the phasic phenomena of REM sleep, rather than to the REM sleep state per se."}
{"id": "PMID:231605", "title": "Development, preparation and safety testing of a Clostridium welchii type C toxoid. I: preliminary observations in man in Papua New Guinea.", "content": "The reactogenicity and immunogenicity of various strengths of plain and adsorbed Cl. welchii type C toxoid have been evaluated in laboratory tests and in man in Papua New Guinea. The greater antigenicity and acceptable clinical reactivity of a vaccine containing 50 total combining power units per 0.5 mm of adsorbed toxoid resulted in its selection for further field studies.", "contents": "Development, preparation and safety testing of a Clostridium welchii type C toxoid. I: preliminary observations in man in Papua New Guinea. The reactogenicity and immunogenicity of various strengths of plain and adsorbed Cl. welchii type C toxoid have been evaluated in laboratory tests and in man in Papua New Guinea. The greater antigenicity and acceptable clinical reactivity of a vaccine containing 50 total combining power units per 0.5 mm of adsorbed toxoid resulted in its selection for further field studies."}
{"id": "PMID:231607", "title": "Development, preparation and safety testing of a Clostridium welchii type C toxoid. II. Laboratory evaluation of potency.", "content": "The results obtained with four laboratory tests on four candidate formulations of Clostridium welchii type C vaccine for use in man have been compared with clinical responses to the same vaccines. Quantal response assays in mice appeared to reflect the ranking of the four vaccines in human subjects better than did the guinea pig tests. They also enabled the potency of the vaccine preparations to be related to an existing International Reference Preparation. Mouse assays in which the animals received two spaced doses of vaccine prior to challenge yielded marginally more satisfactory results in terms of precision and reflection of human responses than did assays involving a single dose of vaccine.", "contents": "Development, preparation and safety testing of a Clostridium welchii type C toxoid. II. Laboratory evaluation of potency. The results obtained with four laboratory tests on four candidate formulations of Clostridium welchii type C vaccine for use in man have been compared with clinical responses to the same vaccines. Quantal response assays in mice appeared to reflect the ranking of the four vaccines in human subjects better than did the guinea pig tests. They also enabled the potency of the vaccine preparations to be related to an existing International Reference Preparation. Mouse assays in which the animals received two spaced doses of vaccine prior to challenge yielded marginally more satisfactory results in terms of precision and reflection of human responses than did assays involving a single dose of vaccine."}
{"id": "PMID:231608", "title": "The effects of EGTA and trypsin on the serum requirements for cell attachment to collagens.", "content": "Cells growing on plastic or glass surfaces in vitro may be brought into suspension by proteases (e.g. trypsin) or chelating agents (e.g. EGTA). Trypsin and EGTA remove different quantities and types of molecules from cell surfaces. Previous studies have revealed that when confluent cultures of either BHK or PyBHK cells are brought into suspension by exposure to trypsin, foetal calf serum (or fibronectin) is required for cell attachment to films of denature type I collagen, but not to 3-dimensional gels of native collagen fibres. In this communication the serum requirements for the attachment of BHK and PyBHK cells to collagen substrata have been examined as a function of (a) the method used to prepare the cell suspension (EGTA or trypsin), and (b) cell density. Data are presented consistent with the view that cell surface-associated fibronectin is able to mediate cell attachment directly to films of denatured collagen.", "contents": "The effects of EGTA and trypsin on the serum requirements for cell attachment to collagens. Cells growing on plastic or glass surfaces in vitro may be brought into suspension by proteases (e.g. trypsin) or chelating agents (e.g. EGTA). Trypsin and EGTA remove different quantities and types of molecules from cell surfaces. Previous studies have revealed that when confluent cultures of either BHK or PyBHK cells are brought into suspension by exposure to trypsin, foetal calf serum (or fibronectin) is required for cell attachment to films of denature type I collagen, but not to 3-dimensional gels of native collagen fibres. In this communication the serum requirements for the attachment of BHK and PyBHK cells to collagen substrata have been examined as a function of (a) the method used to prepare the cell suspension (EGTA or trypsin), and (b) cell density. Data are presented consistent with the view that cell surface-associated fibronectin is able to mediate cell attachment directly to films of denatured collagen."}
{"id": "PMID:231610", "title": "Cholinergic inhibition of catecholamine-stimulable cyclic AMP accumulation in murine atria.", "content": "Carbachol antagonizes isoproterenol-stimulable cyclic AMP accumulation in mouse atria by direct activation of cardiac muscarinic receptors. Inhibition by carbachol occurs rapidly and is completely reversed when the drug is removed. Neither nitroprusside nor 8-bromo-cyclic GMP mimics the actions of carbachol and low concentrations of carbachol block cyclic AMP accumulation without increasing the intracellular cyclic GMP content. Carbachol does not block cyclic AMP accumulation by activating phosphodiesterase since it is fully effective in the face of marked phosphodiesterase inhibition, nor does it appear to inhibit the catalytic activity of adenylate cyclase since it does not decrease either basal or cholera toxin-stimulated cyclic AMP accumulation. The interaction between carbachol and isoproterenol is not competitive, since cholinergic inhibition cannot be surmounted by increasing concentrations of isoproterenol. The site of muscarinic action therefore appears to involve the mechanisms coupling the hormone-receptor complex to adenylate cyclase. This site is distinct from that of cholera toxin action since there is no antagonism between the effects of cholera toxin and carbachol on cyclic AMP metabolism in the atrium.", "contents": "Cholinergic inhibition of catecholamine-stimulable cyclic AMP accumulation in murine atria. Carbachol antagonizes isoproterenol-stimulable cyclic AMP accumulation in mouse atria by direct activation of cardiac muscarinic receptors. Inhibition by carbachol occurs rapidly and is completely reversed when the drug is removed. Neither nitroprusside nor 8-bromo-cyclic GMP mimics the actions of carbachol and low concentrations of carbachol block cyclic AMP accumulation without increasing the intracellular cyclic GMP content. Carbachol does not block cyclic AMP accumulation by activating phosphodiesterase since it is fully effective in the face of marked phosphodiesterase inhibition, nor does it appear to inhibit the catalytic activity of adenylate cyclase since it does not decrease either basal or cholera toxin-stimulated cyclic AMP accumulation. The interaction between carbachol and isoproterenol is not competitive, since cholinergic inhibition cannot be surmounted by increasing concentrations of isoproterenol. The site of muscarinic action therefore appears to involve the mechanisms coupling the hormone-receptor complex to adenylate cyclase. This site is distinct from that of cholera toxin action since there is no antagonism between the effects of cholera toxin and carbachol on cyclic AMP metabolism in the atrium."}
{"id": "PMID:231611", "title": "Characterization of immunofluorescent cyclic GMP-positive fibres in the central nervous system.", "content": "The cyclic GMP immunofluorescent fibres in the rat central nervous system have been characterized as processes of fibrous astrocytes, on the basis of distribution and similarity to the localization of glial fibrillary acidic protein. The neuroglial localization of the nucleotide is discussed together with the surprising observation that these cyclic GMP positive fibres are absent from the central nervous system of the adult mouse.", "contents": "Characterization of immunofluorescent cyclic GMP-positive fibres in the central nervous system. The cyclic GMP immunofluorescent fibres in the rat central nervous system have been characterized as processes of fibrous astrocytes, on the basis of distribution and similarity to the localization of glial fibrillary acidic protein. The neuroglial localization of the nucleotide is discussed together with the surprising observation that these cyclic GMP positive fibres are absent from the central nervous system of the adult mouse."}
{"id": "PMID:231612", "title": "Prostacyclin increases cAMP in coronary arteries.", "content": "This study was designed to determine whether prostacyclin (PGI2)-induced relaxation in circular strips of coronary arteries might be mediated by cAMP. Partially depolarized circular strips of bovine coronary arteries were used and PGI2-induced changes in length were compared with tissue concentrations of cAMP and cGMP, measured by RIA. It was found that PGI2 produced significant and concentration dependent increases in cAMP levels which were closely associated with the relaxant effects produced by the same concentrations (0.3 - 26.7 muM). Cyclic GMP was not changed by these concentrations. The relaxant effects of PGI2 were not antagonized by propranolol. There was a significant linear correlation between log increases in cAMP and percent relaxation produced by PGI2 which was almost identical with similar correlations obtained with either isoprenaline or adenosine, indicating that the relaxant effects of PGI2 are in analogy to those of isoprenaline and adenosine likely to be mediated by cAMP.", "contents": "Prostacyclin increases cAMP in coronary arteries. This study was designed to determine whether prostacyclin (PGI2)-induced relaxation in circular strips of coronary arteries might be mediated by cAMP. Partially depolarized circular strips of bovine coronary arteries were used and PGI2-induced changes in length were compared with tissue concentrations of cAMP and cGMP, measured by RIA. It was found that PGI2 produced significant and concentration dependent increases in cAMP levels which were closely associated with the relaxant effects produced by the same concentrations (0.3 - 26.7 muM). Cyclic GMP was not changed by these concentrations. The relaxant effects of PGI2 were not antagonized by propranolol. There was a significant linear correlation between log increases in cAMP and percent relaxation produced by PGI2 which was almost identical with similar correlations obtained with either isoprenaline or adenosine, indicating that the relaxant effects of PGI2 are in analogy to those of isoprenaline and adenosine likely to be mediated by cAMP."}
{"id": "PMID:231613", "title": "Assay for vitamin D2 and vitamin D3 in plasma of dairy cows: changes after massive dosing of vitamin D3.", "content": "A sensitive, precise assay for vitamin D in plasma is described. Three to five milliliters of plasma were extracted with methanol:methylene chloride (2:1). The lipid extract was chromatographed on Sephadex LH-20 and then on lipidex-5000 columns. After high pressure liquid chromatography with a reverse phase chromatographic system, vitamin D2 and vitamin D3 were quantitated by ultraviolet absorbance. We used this assay system for monitoring daily changes of vitamin D3 in plasma of two Jersey cows after four intramuscular doses (15 x 10(6) IU) of vitamin D3 administered at weekly intervals. Basal vitamin D in plasma was 3.2 +/- .99 ng/ml with a range of 1.7 to 4.9 ng/ml. Vitamin D3 in plasma remained relatively low (10 to 45 ng/ml) the week after the first vitamin D3 injection. Vitamin D3 was high (130 to 234 ng/ml) after the second, third, and fourth injections. Vitamin D3 decreased steadily to 88 ng/ml by 38 days after the fourth vitamin D3 injection. Phosphorus in plasma increased sharply to a plateau at 9.5 mg/100 ml during the week after the second vitamin D3 injection and returned to normal (4.5 mg/100 ml) at the end of the experiment. Calcium, however, gradually increased to 14.0 mg/100 ml 20 days after the fourth vitamin D3 injection. Both animals remained hypercalcemic (calcium 11.5 mg/100 ml) during the experiment.", "contents": "Assay for vitamin D2 and vitamin D3 in plasma of dairy cows: changes after massive dosing of vitamin D3. A sensitive, precise assay for vitamin D in plasma is described. Three to five milliliters of plasma were extracted with methanol:methylene chloride (2:1). The lipid extract was chromatographed on Sephadex LH-20 and then on lipidex-5000 columns. After high pressure liquid chromatography with a reverse phase chromatographic system, vitamin D2 and vitamin D3 were quantitated by ultraviolet absorbance. We used this assay system for monitoring daily changes of vitamin D3 in plasma of two Jersey cows after four intramuscular doses (15 x 10(6) IU) of vitamin D3 administered at weekly intervals. Basal vitamin D in plasma was 3.2 +/- .99 ng/ml with a range of 1.7 to 4.9 ng/ml. Vitamin D3 in plasma remained relatively low (10 to 45 ng/ml) the week after the first vitamin D3 injection. Vitamin D3 was high (130 to 234 ng/ml) after the second, third, and fourth injections. Vitamin D3 decreased steadily to 88 ng/ml by 38 days after the fourth vitamin D3 injection. Phosphorus in plasma increased sharply to a plateau at 9.5 mg/100 ml during the week after the second vitamin D3 injection and returned to normal (4.5 mg/100 ml) at the end of the experiment. Calcium, however, gradually increased to 14.0 mg/100 ml 20 days after the fourth vitamin D3 injection. Both animals remained hypercalcemic (calcium 11.5 mg/100 ml) during the experiment."}
{"id": "PMID:231614", "title": "Adrenal response to adrenocorticotropin in Holstein heifers exposed to a cool environment.", "content": "Tne Holstein heifers acclimated to either -2.7 or 19.1 C were used to determine glucocorticoid concentrations in plasma following injection of adrenocorticotropin (200 IU). Environmental treatments did not change glucocorticoids following adrenococorticotropin. Adrenocorticotropin injection elevated mean glucocorticoids to 41.6 ng/ml plasma at -2.7 C and 42.8 ng/ml at 19.1 C. Adrenal response to adrenocorticotropin in Holstein heifers was not altered by low environmental temperature.", "contents": "Adrenal response to adrenocorticotropin in Holstein heifers exposed to a cool environment. Tne Holstein heifers acclimated to either -2.7 or 19.1 C were used to determine glucocorticoid concentrations in plasma following injection of adrenocorticotropin (200 IU). Environmental treatments did not change glucocorticoids following adrenococorticotropin. Adrenocorticotropin injection elevated mean glucocorticoids to 41.6 ng/ml plasma at -2.7 C and 42.8 ng/ml at 19.1 C. Adrenal response to adrenocorticotropin in Holstein heifers was not altered by low environmental temperature."}
{"id": "PMID:231623", "title": "The spread of rhinoviruses in the Soviet Union (USSR) and in Czechoslovakia (CSSR) and the role of their pathology.", "content": "Virological, serological and immunofluorescence studies revealed circulation of rhinoviruses of the strains 1A, 1B, 2, 3, 7, 9, 10, 12, 13, 14, 16-23, 27, 29-33, 42, 48, 53, 56, 60 and 69 on the territory of Czechoslovakia and the Soviet Union. According to virological results, type 48 predominated and was followed in frequency of occurrence by types 27, 14 and 16 in the USSR and 30, 1A and 31 in the CSSR. RV infection in adults with ARD diseases was the aetiology in 28.5% of cases. Among the causative agents of acute rhinitis, rhinosinusitis and otitis, rhinovirus infection makes up a large proportion. Interrelation has been found between rhinovirus infection and chronic inflammation of the mucosa of the nose, the accessory sinuses and the ears. Prolonged course of rhinovirus infection and isolation of the virus in the late stages of disease (1-4 months after its onset) support the presumption that rhinoviruses promote chronicity of inflammation. RV was isolated from patients with chronic pneumonia from the lower respiratory passages (bronchial secretion). Rhinoviraemia was found in a child who died of ARD.", "contents": "The spread of rhinoviruses in the Soviet Union (USSR) and in Czechoslovakia (CSSR) and the role of their pathology. Virological, serological and immunofluorescence studies revealed circulation of rhinoviruses of the strains 1A, 1B, 2, 3, 7, 9, 10, 12, 13, 14, 16-23, 27, 29-33, 42, 48, 53, 56, 60 and 69 on the territory of Czechoslovakia and the Soviet Union. According to virological results, type 48 predominated and was followed in frequency of occurrence by types 27, 14 and 16 in the USSR and 30, 1A and 31 in the CSSR. RV infection in adults with ARD diseases was the aetiology in 28.5% of cases. Among the causative agents of acute rhinitis, rhinosinusitis and otitis, rhinovirus infection makes up a large proportion. Interrelation has been found between rhinovirus infection and chronic inflammation of the mucosa of the nose, the accessory sinuses and the ears. Prolonged course of rhinovirus infection and isolation of the virus in the late stages of disease (1-4 months after its onset) support the presumption that rhinoviruses promote chronicity of inflammation. RV was isolated from patients with chronic pneumonia from the lower respiratory passages (bronchial secretion). Rhinoviraemia was found in a child who died of ARD."}
{"id": "PMID:231624", "title": "Immunological surveys of antibodies against B. pertussis and B. parapertussis in some African and Asian countries.", "content": "Immunological surveys in African and Asian countries showed a different degree of herd immunity in the respective countries and the circulation of various types of B. pertussis. Antibodies against B. parapertussis, the second aertiological agent of whooping cough, were found in all countries in all age groups. Before planning any vaccination program, attention should be paid to the vaccine concerning the content of all types of B. pertussis, as was shown in the results of the testing of different vaccines used in Mongolia and Algeria. It is also possible to estimate the age limit for vaccination and thus economic use of the vaccine. The contemporary state of reporting whooping cough cases is very unsatisfactory.", "contents": "Immunological surveys of antibodies against B. pertussis and B. parapertussis in some African and Asian countries. Immunological surveys in African and Asian countries showed a different degree of herd immunity in the respective countries and the circulation of various types of B. pertussis. Antibodies against B. parapertussis, the second aertiological agent of whooping cough, were found in all countries in all age groups. Before planning any vaccination program, attention should be paid to the vaccine concerning the content of all types of B. pertussis, as was shown in the results of the testing of different vaccines used in Mongolia and Algeria. It is also possible to estimate the age limit for vaccination and thus economic use of the vaccine. The contemporary state of reporting whooping cough cases is very unsatisfactory."}
{"id": "PMID:231616", "title": "Evidence of specific nuclear binding sites for T3 in the mouse cultured fibroblast.", "content": "Mouse L 929 cultured fibroblasts revealed saturable and high affinity nuclear receptors for triiodothyronine. 125I-T3 bound rapidly to intact cells, with a steady state achieved between 1-2 h at 37 C. By Scatchard estimation, the maximal binding capacity averaged 18 fentomoles of T3 bound per 100 microgram of DNA, which approximated to 2,000 sites per cell nucleus; the apparent equilibrium association constant Ka averaged 4.90 x 109 LM-1. The relative affinity of T3 analogs tested correlated with their respective thyromimetic potency. Limited capacity, high affinity and specificity of T3 nuclear receptors in these fibroblasts were found to have properties similar to those previously observed in other cell lines or tissues. Such cultured fibroblasts may provide a useful experimental model to investigate the intracellular biological effects of thyroid hormones.", "contents": "Evidence of specific nuclear binding sites for T3 in the mouse cultured fibroblast. Mouse L 929 cultured fibroblasts revealed saturable and high affinity nuclear receptors for triiodothyronine. 125I-T3 bound rapidly to intact cells, with a steady state achieved between 1-2 h at 37 C. By Scatchard estimation, the maximal binding capacity averaged 18 fentomoles of T3 bound per 100 microgram of DNA, which approximated to 2,000 sites per cell nucleus; the apparent equilibrium association constant Ka averaged 4.90 x 109 LM-1. The relative affinity of T3 analogs tested correlated with their respective thyromimetic potency. Limited capacity, high affinity and specificity of T3 nuclear receptors in these fibroblasts were found to have properties similar to those previously observed in other cell lines or tissues. Such cultured fibroblasts may provide a useful experimental model to investigate the intracellular biological effects of thyroid hormones."}
{"id": "PMID:231627", "title": "Induction of androgen-dependent protease and serous-like granules by tri-iodothyronine in the submandibular gland of mice with testicular feminization.", "content": "Esteroprotease, an androgen-dependent enzyme of the mouse submandibular gland, was increased by injection of tri-iodothyronine (T3) in mice with testicular feminization (Tfm) which are genetically deficient in androgen receptors. Histochemical and electron microscopic studies also demonstrated increases of RNA and serous-like granules in cells of the convoluted tubules of the gland. These findings suggest that the esteroprotease gene in Tfm mice is normal and that T3 can induced both esteroprotease and serous-like granules independently of androgen.", "contents": "Induction of androgen-dependent protease and serous-like granules by tri-iodothyronine in the submandibular gland of mice with testicular feminization. Esteroprotease, an androgen-dependent enzyme of the mouse submandibular gland, was increased by injection of tri-iodothyronine (T3) in mice with testicular feminization (Tfm) which are genetically deficient in androgen receptors. Histochemical and electron microscopic studies also demonstrated increases of RNA and serous-like granules in cells of the convoluted tubules of the gland. These findings suggest that the esteroprotease gene in Tfm mice is normal and that T3 can induced both esteroprotease and serous-like granules independently of androgen."}
{"id": "PMID:231628", "title": "Properties of rat adrenal zona reticularis cells: production and stimulation of certain steroids.", "content": "The outputs of corticosterone, deoxycorticosterone and androstenedione from dispersed, purified rat adrenal zona reticularis and zona fasciculata cells have been measured by radioimmunoassay. Preferential production of deoxycorticosterone by zona reticularis cells was demonstrated by their higher basal deoxycorticosterone : corticosterone ratio when compared with zona fasciculata cells. Adrencorticotrophin (ACTH) stimulated corticosterone output by all cell pools prepared by unit gravity (1 g) sedimentation, zona fasciculata cells being stimulated 130-fold compared with 20-fold for the zona reticularis cells in relation to their basal corticosterone output. In every cell pool, ACTH stimulated the output corticosterone more than it stimulated the output of deoxycorticosterone. In parallel cell preparations, it was shown that ACTH increased the conversion of tracer amounts of radioactive deoxycorticosterone to corticosterone and decreased the conversion of radioactive corticosterone to 11-dehydrocorticosterone. Adrenocorticotrophin did not increase the conversion of radioactive deoxycorticosterone to total 11-oxygenated steroids (corticosterone + 11-dehydrocorticosterone). It is unlikely therefore that ACTH stimulates 11 beta-hydroxylation. Data indicate that the ratio of deoxycorticosterone to total 11-oxygenated steroids (corticosterone + 11-dehydrocorticosterone) is characteristic for each cell type, and that this ratio will be relatively independent of ACTH stimulation or the amount of pregnenolone substrate available. Basal androstenedione outputs were similar for both types of cell, and ACTH stimulation was very small, being slightly greater for zona fasciculata than for zona reticularis cells. The contribution of the zona reticularis cells to the basal output of any steroid by the cells of the inner two zones of the adrenal cortex of the rat was relatively small (20% for deoxycorticosterone and 10% for corticosterone) and was even less after stimulation by ACTH. Unless a specific stimulus can be found, therefore, a significant role for the zona reticularis cannot yet be established.", "contents": "Properties of rat adrenal zona reticularis cells: production and stimulation of certain steroids. The outputs of corticosterone, deoxycorticosterone and androstenedione from dispersed, purified rat adrenal zona reticularis and zona fasciculata cells have been measured by radioimmunoassay. Preferential production of deoxycorticosterone by zona reticularis cells was demonstrated by their higher basal deoxycorticosterone : corticosterone ratio when compared with zona fasciculata cells. Adrencorticotrophin (ACTH) stimulated corticosterone output by all cell pools prepared by unit gravity (1 g) sedimentation, zona fasciculata cells being stimulated 130-fold compared with 20-fold for the zona reticularis cells in relation to their basal corticosterone output. In every cell pool, ACTH stimulated the output corticosterone more than it stimulated the output of deoxycorticosterone. In parallel cell preparations, it was shown that ACTH increased the conversion of tracer amounts of radioactive deoxycorticosterone to corticosterone and decreased the conversion of radioactive corticosterone to 11-dehydrocorticosterone. Adrenocorticotrophin did not increase the conversion of radioactive deoxycorticosterone to total 11-oxygenated steroids (corticosterone + 11-dehydrocorticosterone). It is unlikely therefore that ACTH stimulates 11 beta-hydroxylation. Data indicate that the ratio of deoxycorticosterone to total 11-oxygenated steroids (corticosterone + 11-dehydrocorticosterone) is characteristic for each cell type, and that this ratio will be relatively independent of ACTH stimulation or the amount of pregnenolone substrate available. Basal androstenedione outputs were similar for both types of cell, and ACTH stimulation was very small, being slightly greater for zona fasciculata than for zona reticularis cells. The contribution of the zona reticularis cells to the basal output of any steroid by the cells of the inner two zones of the adrenal cortex of the rat was relatively small (20% for deoxycorticosterone and 10% for corticosterone) and was even less after stimulation by ACTH. Unless a specific stimulus can be found, therefore, a significant role for the zona reticularis cannot yet be established."}
{"id": "PMID:231629", "title": "Occupations of fathers of patients with Wilms's tumour.", "content": "A case-control study of 149 Connecticut-born children with Wilms's tumour reported to the Connecticut Tumor Registry during the period 1935--1973 and of 149 matched controls was undertaken in order to explore the possibility that children with Wilms's tumour may have been exposed perinatally to carcinogenic agents. The occupation of the father at the time of the child's birth was investigated and used as an indicator of potential sources of carcinogens to which infants in the study may have been exposed. An association was found between paternal occupations related to lead in the group developing Wilms's tumour compared with the controls.", "contents": "Occupations of fathers of patients with Wilms's tumour. A case-control study of 149 Connecticut-born children with Wilms's tumour reported to the Connecticut Tumor Registry during the period 1935--1973 and of 149 matched controls was undertaken in order to explore the possibility that children with Wilms's tumour may have been exposed perinatally to carcinogenic agents. The occupation of the father at the time of the child's birth was investigated and used as an indicator of potential sources of carcinogens to which infants in the study may have been exposed. An association was found between paternal occupations related to lead in the group developing Wilms's tumour compared with the controls."}
{"id": "PMID:231631", "title": "Responses of the early chick embryo to external cAMP sources.", "content": "Early chick embryos were stimulated with local sources of cAMP. Three major effects were observed: bending of the embryonic axis, attraction of cells on the ventral surface of the embryo, and disruption of the blastodisc. Each had a characteristic concentration dependence. These results are compared with those from studies of cells disaggregated from similar embryos.", "contents": "Responses of the early chick embryo to external cAMP sources. Early chick embryos were stimulated with local sources of cAMP. Three major effects were observed: bending of the embryonic axis, attraction of cells on the ventral surface of the embryo, and disruption of the blastodisc. Each had a characteristic concentration dependence. These results are compared with those from studies of cells disaggregated from similar embryos."}
{"id": "PMID:231632", "title": "Neuromuscular transmission in Peripatus.", "content": "The electrical and mechanical responses of body, leg and jaw muscle of Peripatus to electrical excitation of their motor-nerves were examined. A small twitch was obtained from each muscle, whose strength increased stepwise with increasing stimulus strength. In jaw and body muscles as many as ten increments in height were obtained with increasing stimulus strength. Only a single twitch height was obtained from the claw retractor muscle. Tetanus:twitch ratio under supraminal stimulation was less than 2:1 for jaw muscles, about 50:1 for the claw retractor and about 6:1 for muscles moving the legs. The jaw-muscle twitch duration was 0.6 s, that for the leg muscles 1.2 s and for body muscles about 3.0 s. Large miniature junctional potentials were frequently recorded regardless of electrode location. Responses to neural stimulation consing stimulus strength, generally with three steps. With repetitive stimulation, facilitation of the second and third junctional potentials occurred, plus summation. A few fibres gave spikes to a single shock: most gave a few spikes sporadically, during repetitive stimulation only. No abrupt tension increments occurred in whole muscles when individual fibres spiked. We saw no evidence for peripheral inhibitory axons. The excitation of Peripatus muscle is by local graded junctional potentials at distributed nerve-on-muscle fibre synapses, together with action potentials. The latter are initiated only by larger junctional potentials compounded of multiple smaller ones summated and/or facilitated. The details of neuromuscular physiology are not compatible with the phylogenetic status commonly proposed for Peripatus.", "contents": "Neuromuscular transmission in Peripatus. The electrical and mechanical responses of body, leg and jaw muscle of Peripatus to electrical excitation of their motor-nerves were examined. A small twitch was obtained from each muscle, whose strength increased stepwise with increasing stimulus strength. In jaw and body muscles as many as ten increments in height were obtained with increasing stimulus strength. Only a single twitch height was obtained from the claw retractor muscle. Tetanus:twitch ratio under supraminal stimulation was less than 2:1 for jaw muscles, about 50:1 for the claw retractor and about 6:1 for muscles moving the legs. The jaw-muscle twitch duration was 0.6 s, that for the leg muscles 1.2 s and for body muscles about 3.0 s. Large miniature junctional potentials were frequently recorded regardless of electrode location. Responses to neural stimulation consing stimulus strength, generally with three steps. With repetitive stimulation, facilitation of the second and third junctional potentials occurred, plus summation. A few fibres gave spikes to a single shock: most gave a few spikes sporadically, during repetitive stimulation only. No abrupt tension increments occurred in whole muscles when individual fibres spiked. We saw no evidence for peripheral inhibitory axons. The excitation of Peripatus muscle is by local graded junctional potentials at distributed nerve-on-muscle fibre synapses, together with action potentials. The latter are initiated only by larger junctional potentials compounded of multiple smaller ones summated and/or facilitated. The details of neuromuscular physiology are not compatible with the phylogenetic status commonly proposed for Peripatus."}
{"id": "PMID:231633", "title": "Acute and chronic hypoxia in rats. II. Effect on oxidative phosphorylation and in vitro protein synthesis in liver mitochondria and its subpopulations.", "content": "The objective of this investigation was to examine liver mitochondrial functions in rats exposed to 0.4 atm for 0, 5 and 27 days, Liver homogenates were fractionated by rate-zonal centrifugation utilizing iso-osmotic Ficoll-sucrose gradients; this eliminates loss of large and small mitochondria and makes possible the separation of mitochondria into subpopulations according to sedimentation coefficient. After pooling all mitochondrial fractions for obtaining composite determinations of the entire population, large diminutions in states 3 and 4 respiration (succinate as substrate) were obtained in day-5 and day-27 rats but no changes were evident with regard to ADP:O ratios, respiratory control indices or the capacity for in vitro protein synthesis. By examination of subpopulations of mitochondria, it was found that mitochondria are heterogeneous with regard to ADP:O ratios, respiratory control indices, states 3 and 4 respiration and the capacity for in vitro protein synthesis. The heterogeneity for each of these parameters was altered in day-5 and day-27 animals. Although states 3 and 4 respiration were depressed throughout the entire mitochondrial population for day-5 and day-27 rats, a subpopulation of mitochondria from day-27 rats showed respiratory control indices and ADP:O ratios which were higher than any subpopulation of mitochondria of either day-5 or day-0 animals.", "contents": "Acute and chronic hypoxia in rats. II. Effect on oxidative phosphorylation and in vitro protein synthesis in liver mitochondria and its subpopulations. The objective of this investigation was to examine liver mitochondrial functions in rats exposed to 0.4 atm for 0, 5 and 27 days, Liver homogenates were fractionated by rate-zonal centrifugation utilizing iso-osmotic Ficoll-sucrose gradients; this eliminates loss of large and small mitochondria and makes possible the separation of mitochondria into subpopulations according to sedimentation coefficient. After pooling all mitochondrial fractions for obtaining composite determinations of the entire population, large diminutions in states 3 and 4 respiration (succinate as substrate) were obtained in day-5 and day-27 rats but no changes were evident with regard to ADP:O ratios, respiratory control indices or the capacity for in vitro protein synthesis. By examination of subpopulations of mitochondria, it was found that mitochondria are heterogeneous with regard to ADP:O ratios, respiratory control indices, states 3 and 4 respiration and the capacity for in vitro protein synthesis. The heterogeneity for each of these parameters was altered in day-5 and day-27 animals. Although states 3 and 4 respiration were depressed throughout the entire mitochondrial population for day-5 and day-27 rats, a subpopulation of mitochondria from day-27 rats showed respiratory control indices and ADP:O ratios which were higher than any subpopulation of mitochondria of either day-5 or day-0 animals."}
{"id": "PMID:231636", "title": "The nonlinear pathway of Y ganglion cells in the cat retina.", "content": "Retinal ganglion cells of the Y type in the cat retina produce two different types of response: linear and nonlinear. The nonlinear responses are generated by a separate and independent nonlinear pathway. The functional connectivity in this pathway is analyzed here by comparing the observed second-order frequency responses of Y cells with predictions of a \"sandwich model\" in which a static nonlinear stage is sandwiched between two linear filters. The model agrees well with the qualitative and quantitative features of the second-order responses. The prefilter in the model may well be the bipolar cells and the nonlinearity and postfilter in the model are probably associated with amacrine cells.", "contents": "The nonlinear pathway of Y ganglion cells in the cat retina. Retinal ganglion cells of the Y type in the cat retina produce two different types of response: linear and nonlinear. The nonlinear responses are generated by a separate and independent nonlinear pathway. The functional connectivity in this pathway is analyzed here by comparing the observed second-order frequency responses of Y cells with predictions of a \"sandwich model\" in which a static nonlinear stage is sandwiched between two linear filters. The model agrees well with the qualitative and quantitative features of the second-order responses. The prefilter in the model may well be the bipolar cells and the nonlinearity and postfilter in the model are probably associated with amacrine cells."}
{"id": "PMID:231637", "title": "Labeling of hepatitis B virus surface antigen (HBsAg) synthesized in a HBsAg-producing hepatoma cell line.", "content": "Hepatitis B virus surface antigen (HBsAg) could be studied until recently only by isolating it from the blood of carriers, thus making incorporation of radioactive precursors into this protein(s) impossible. The isolation of a cell line producing HBsAg [Alexander et al, 1978] has eliminated this obstacle. The cell line was therefore used for labeling HBsAg either with 35S-methionine or with 35S-cystine. HBsAg was purified by pelleting the component and by isopycnic centrifugation in CsCl gradients. HBsAg-positive fractions (as determined by solid-phase radioimmunoassay) were isolated from the gradients and analyzed in sodium dodecyl sulfate-containing polyacrylamide gels. It was found that although HBsAg contains substantial amounts of 35S-cystine, very little 35S-methionine was incorporated into this protein. In contrast, both labels were found in other structures having a buoyant density of about 1.3 gm/cm3 in CsCl. It was concluded that HBsAg is very low in methionine, and therefore this amino acid should not be used for labeling HBsAg in cells or in a cell-free system. Analysis of 35S-cystine-labeled HBsAg-positive material (buoyant density about 1.2 gm/cm3 in CsCl) revealed five proteins with molecular weights in the range of 48,000-82,000.", "contents": "Labeling of hepatitis B virus surface antigen (HBsAg) synthesized in a HBsAg-producing hepatoma cell line. Hepatitis B virus surface antigen (HBsAg) could be studied until recently only by isolating it from the blood of carriers, thus making incorporation of radioactive precursors into this protein(s) impossible. The isolation of a cell line producing HBsAg [Alexander et al, 1978] has eliminated this obstacle. The cell line was therefore used for labeling HBsAg either with 35S-methionine or with 35S-cystine. HBsAg was purified by pelleting the component and by isopycnic centrifugation in CsCl gradients. HBsAg-positive fractions (as determined by solid-phase radioimmunoassay) were isolated from the gradients and analyzed in sodium dodecyl sulfate-containing polyacrylamide gels. It was found that although HBsAg contains substantial amounts of 35S-cystine, very little 35S-methionine was incorporated into this protein. In contrast, both labels were found in other structures having a buoyant density of about 1.3 gm/cm3 in CsCl. It was concluded that HBsAg is very low in methionine, and therefore this amino acid should not be used for labeling HBsAg in cells or in a cell-free system. Analysis of 35S-cystine-labeled HBsAg-positive material (buoyant density about 1.2 gm/cm3 in CsCl) revealed five proteins with molecular weights in the range of 48,000-82,000."}
{"id": "PMID:231639", "title": "The mode of action alginic acid compound in the reduction of gastroesophageal reflux.", "content": "This study was designed to evaluate quantitatively the mode of action of alginic acid compound (AAC) in the treatment of patients with symptomatic gastroesophageal reflux. Gastroesophageal scintigraphy using an orall administered Tc-99m sulfur colloid solution was used to demonstrate that AAC decreased significantly the gastroesophageal reflux index from (9.9 +/- 1.3) % to (6.5 +/- 0.8) % (p less than 0.05). No alteration of lower esophageal sphincter pressure was observed. After ACC was suitably labeled with Sr-87m, a dual-nuclide scintigraphic technique was used to show that most (greater than 75%) of the AAC was located in the upper half of the stomach in both normal subjects and patients with gastroesophageal reflux. In those subjects in whom reflux did occur after treatment with AAC, the Sr-87m-AAC refluxed into the esophagus preferentially compared with the liquid containing Tc-99m sulfur colloid. These findings suggest that AAC dimishes gastroesophageal reflux by means of its foaming, floating, and viscous properties.", "contents": "The mode of action alginic acid compound in the reduction of gastroesophageal reflux. This study was designed to evaluate quantitatively the mode of action of alginic acid compound (AAC) in the treatment of patients with symptomatic gastroesophageal reflux. Gastroesophageal scintigraphy using an orall administered Tc-99m sulfur colloid solution was used to demonstrate that AAC decreased significantly the gastroesophageal reflux index from (9.9 +/- 1.3) % to (6.5 +/- 0.8) % (p less than 0.05). No alteration of lower esophageal sphincter pressure was observed. After ACC was suitably labeled with Sr-87m, a dual-nuclide scintigraphic technique was used to show that most (greater than 75%) of the AAC was located in the upper half of the stomach in both normal subjects and patients with gastroesophageal reflux. In those subjects in whom reflux did occur after treatment with AAC, the Sr-87m-AAC refluxed into the esophagus preferentially compared with the liquid containing Tc-99m sulfur colloid. These findings suggest that AAC dimishes gastroesophageal reflux by means of its foaming, floating, and viscous properties."}
{"id": "PMID:231640", "title": "Quantitative lymphoscintigraphy I: Basic concepts for optimal uptake of radiocolloids in the parasternal lymph nodes of rabbits.", "content": "The activity-size distribution of radiocolloids has been studied using gel-chromatography scanning (GCS) of columns filled with Sepharose 4B gel. Rabbits were injected subcutaneously with the colloid of interest, laid supine beneath a gamma camera, and imaged every 15 sec for 2 to 4 hr. From the stored data, the uptakes in the parasternal lymph nodes were analyzed in terms of two-compartment model, and the rate constants measured. The substances tested were Au- 198 colloid, Tc-99m antimony sulfide colloid, Tc-99m tin colloid, Tc-99m phytate, and Tc-99m sulfur colloid. It was shown that the optimal particle size for the colloid in the range 1-10 nm. The large and most rapid uptake was found for Au- 198 colloid, with a particle size of 5 nm, which appeared as a single peak in the GCS spectrum. The percentage uptake after 2 hr for Au- 198 colloid 8%, while it was 5% for antimony-sulfide colloid, which was the best of the Tc-99m-labeled colloids. The GCS spectrum for the antimony product showed a single-peaked size distribution with a somewhat broader range: 5-15 nm. The particles of the other colloids were either too large to pass into the lymphatic system, or too small to be trapped.", "contents": "Quantitative lymphoscintigraphy I: Basic concepts for optimal uptake of radiocolloids in the parasternal lymph nodes of rabbits. The activity-size distribution of radiocolloids has been studied using gel-chromatography scanning (GCS) of columns filled with Sepharose 4B gel. Rabbits were injected subcutaneously with the colloid of interest, laid supine beneath a gamma camera, and imaged every 15 sec for 2 to 4 hr. From the stored data, the uptakes in the parasternal lymph nodes were analyzed in terms of two-compartment model, and the rate constants measured. The substances tested were Au- 198 colloid, Tc-99m antimony sulfide colloid, Tc-99m tin colloid, Tc-99m phytate, and Tc-99m sulfur colloid. It was shown that the optimal particle size for the colloid in the range 1-10 nm. The large and most rapid uptake was found for Au- 198 colloid, with a particle size of 5 nm, which appeared as a single peak in the GCS spectrum. The percentage uptake after 2 hr for Au- 198 colloid 8%, while it was 5% for antimony-sulfide colloid, which was the best of the Tc-99m-labeled colloids. The GCS spectrum for the antimony product showed a single-peaked size distribution with a somewhat broader range: 5-15 nm. The particles of the other colloids were either too large to pass into the lymphatic system, or too small to be trapped."}
{"id": "PMID:231641", "title": "Myocardial uptake of technetium-99m stannous pyrophosphate in experimental viral myopericarditis.", "content": "Distribution of technetium-99m stannous pyrophosphate was studied in mice with experimentally induced viral myopericarditis. Myocardial and bone uptakes of Tc-PPi were compared in 55 mice inoculated with coxsackievirus B3 (Nancy strain). The myocardium-to-bone uptake ratio in 33 mice with myopericarditis was increased to a greater extent than that seen in 22 mice without myopericarditis (p less than 0.001). In the severely involved heart, the uptake per gram exceeded that in the bone. Myocardial uptake in myopericarditis can be visualized on a whole-body image using a pinhole collimator and a left lateral view. Our experimental studies suggest the potential clinical usefulness of myocardial scintigraphy in viral myopericarditis.", "contents": "Myocardial uptake of technetium-99m stannous pyrophosphate in experimental viral myopericarditis. Distribution of technetium-99m stannous pyrophosphate was studied in mice with experimentally induced viral myopericarditis. Myocardial and bone uptakes of Tc-PPi were compared in 55 mice inoculated with coxsackievirus B3 (Nancy strain). The myocardium-to-bone uptake ratio in 33 mice with myopericarditis was increased to a greater extent than that seen in 22 mice without myopericarditis (p less than 0.001). In the severely involved heart, the uptake per gram exceeded that in the bone. Myocardial uptake in myopericarditis can be visualized on a whole-body image using a pinhole collimator and a left lateral view. Our experimental studies suggest the potential clinical usefulness of myocardial scintigraphy in viral myopericarditis."}
{"id": "PMID:231642", "title": "1-aminocyclobutane[11C]carboxylic acid, a potential tumor-seeking agent.", "content": "1-Aminocyclobutane[14C]carboxylic acid [C-14) ACBC] was incorporated preferentially by several tumor types in rats and hamsters. The agent was cleared rapidly from rat blood, attaining its maximum tissue concentrations within 30 min after i.v. injection. Carrier ACBC had little effect on the tissue distribution of (C-14) ACBC. This agent showed no affinity for a Staphylococcus aureus abscess in rats. The total excretion was low, 3.6% in 2 hr. (C-11) ACBC was synthesized in amounts up to 415 mCi (55% chemical yield) using our modified B\u00fccherer-Strecker technique. Forty minutes were required for the two-step synthesis and chromatographic purification. ACBC was found to be nontoxic in three animal species. The radiation dose from (C-11) ACBC should be minimal. (C-11) ACBC thus appears to have good potential as a tumor-seeking agent, particularly when used with a positron emission computed tomograph.", "contents": "1-aminocyclobutane[11C]carboxylic acid, a potential tumor-seeking agent. 1-Aminocyclobutane[14C]carboxylic acid [C-14) ACBC] was incorporated preferentially by several tumor types in rats and hamsters. The agent was cleared rapidly from rat blood, attaining its maximum tissue concentrations within 30 min after i.v. injection. Carrier ACBC had little effect on the tissue distribution of (C-14) ACBC. This agent showed no affinity for a Staphylococcus aureus abscess in rats. The total excretion was low, 3.6% in 2 hr. (C-11) ACBC was synthesized in amounts up to 415 mCi (55% chemical yield) using our modified B\u00fccherer-Strecker technique. Forty minutes were required for the two-step synthesis and chromatographic purification. ACBC was found to be nontoxic in three animal species. The radiation dose from (C-11) ACBC should be minimal. (C-11) ACBC thus appears to have good potential as a tumor-seeking agent, particularly when used with a positron emission computed tomograph."}
{"id": "PMID:231643", "title": "Potential column chromatography generators for ionic Ga-68. I. Inorganic substrates.", "content": "Chemical separations for Ga-68 from Ge-68 using adsorption chromatography on inorganic materials are described. The adsorbents used were TiO2, ZrO2, and SiO2. Distribution coefficients for Ge and Ga on these absorbents were determined as a function of reagent concentration and duration of equilibration. The distribution coefficient (w/w) for Ge on SiO2 reached 250 in 6 N HNO3, whereas Ga was no significantly adsorbed. Therefore, Ga-68 can be collected with a mall volume of 6 N HNO3 eluent. By contrast, large volumes of 1 N HNO3 were necessary to collect Ga-68 from ZrO2, since the KD of Ga under these circumstances was about 50. The Ga-68 eluted from TiO2 was chemically contaminated with titanates and would require additional chemical manipulation in order to make it injectable. All the adsorbents could lead to chromatographic systems that would allow acceptable chemical separations. However, the specific requirements for a radionuclide generator, usable in a hospital environment, make the SiO2-based system the most attractive.", "contents": "Potential column chromatography generators for ionic Ga-68. I. Inorganic substrates. Chemical separations for Ga-68 from Ge-68 using adsorption chromatography on inorganic materials are described. The adsorbents used were TiO2, ZrO2, and SiO2. Distribution coefficients for Ge and Ga on these absorbents were determined as a function of reagent concentration and duration of equilibration. The distribution coefficient (w/w) for Ge on SiO2 reached 250 in 6 N HNO3, whereas Ga was no significantly adsorbed. Therefore, Ga-68 can be collected with a mall volume of 6 N HNO3 eluent. By contrast, large volumes of 1 N HNO3 were necessary to collect Ga-68 from ZrO2, since the KD of Ga under these circumstances was about 50. The Ga-68 eluted from TiO2 was chemically contaminated with titanates and would require additional chemical manipulation in order to make it injectable. All the adsorbents could lead to chromatographic systems that would allow acceptable chemical separations. However, the specific requirements for a radionuclide generator, usable in a hospital environment, make the SiO2-based system the most attractive."}
{"id": "PMID:231644", "title": "Use of blood-pool imaging in evaluation of diffuse activity patterns in technetium-99m pyrophosphate myocardial scintigraphy.", "content": "It has been suggested that diffuse Tc-99m pyrophosphate precordial activity may be due to persistent blood-pool activity in routine delayed views during myocardial imaging. To answer this question, we reviewed myocardial scintigrams recorded 60--90 min following the injection of 12--15 mCi of Tc-99m pyrophosphate for the presence of diffuse precordial activity, and compared these with early images of the blood pool in 265 patients. Diffuse activity in the delayed images was identified in 48 patients: in 20 with acute myocardial infarction and in 28 with no evidence of it. Comparison of these routine delayed images with early views of the blood pool revealed two types of patterns. In patients with acute infarction, 95% had delayed images that were distinguishable from blood pool either because the activity was smaller than the early blood pool, or by the presence of localized activity superimposed on diffuse activity identical to blood pool. In those without infarction, 93% had activity distribution in routine delayed views matching that in the early blood-pool images. The usefulness of the diffuse TcPPi precordial activity in myocardial infarction is improved when early blood-pool imaging is used to exclude persistence of blood-pool activity as its cause. Moreover, it does not require additional amounts of radioactivity nor complex computer processing, a feature that may be of value in the community hospital using the technique to \"rule out\" infarction 24--72 hr after onset of suggestive symptoms.", "contents": "Use of blood-pool imaging in evaluation of diffuse activity patterns in technetium-99m pyrophosphate myocardial scintigraphy. It has been suggested that diffuse Tc-99m pyrophosphate precordial activity may be due to persistent blood-pool activity in routine delayed views during myocardial imaging. To answer this question, we reviewed myocardial scintigrams recorded 60--90 min following the injection of 12--15 mCi of Tc-99m pyrophosphate for the presence of diffuse precordial activity, and compared these with early images of the blood pool in 265 patients. Diffuse activity in the delayed images was identified in 48 patients: in 20 with acute myocardial infarction and in 28 with no evidence of it. Comparison of these routine delayed images with early views of the blood pool revealed two types of patterns. In patients with acute infarction, 95% had delayed images that were distinguishable from blood pool either because the activity was smaller than the early blood pool, or by the presence of localized activity superimposed on diffuse activity identical to blood pool. In those without infarction, 93% had activity distribution in routine delayed views matching that in the early blood-pool images. The usefulness of the diffuse TcPPi precordial activity in myocardial infarction is improved when early blood-pool imaging is used to exclude persistence of blood-pool activity as its cause. Moreover, it does not require additional amounts of radioactivity nor complex computer processing, a feature that may be of value in the community hospital using the technique to \"rule out\" infarction 24--72 hr after onset of suggestive symptoms."}
{"id": "PMID:231645", "title": "Ovarian imaging by the binding of radioiodinated chorionic gonadotropin: concise communication.", "content": "Previous studies have demonstrated the presence of specific, high-affinity receptors for human chorionic gonadotropin (HCG) in human and rat ovaries. In the present study, highly purified HCG was labeled with iodine-131 and used for the imaging of luteinized rat ovaries. Excellent images were obtained. The accumulation of radioactivity in the ovaries was completely inhibited by previous administration of excess unlabeled HCG. Time-course studies show that radioiodinated HCG was rapidly accumulated within 1 hr and largely cleared from the ovary at 24 hr. These results show the potential for imaging of endocrine target tissues by hormone-receptor binding, and the possibility of quantitation of hormone receptors in tissues under pathological conditions.", "contents": "Ovarian imaging by the binding of radioiodinated chorionic gonadotropin: concise communication. Previous studies have demonstrated the presence of specific, high-affinity receptors for human chorionic gonadotropin (HCG) in human and rat ovaries. In the present study, highly purified HCG was labeled with iodine-131 and used for the imaging of luteinized rat ovaries. Excellent images were obtained. The accumulation of radioactivity in the ovaries was completely inhibited by previous administration of excess unlabeled HCG. Time-course studies show that radioiodinated HCG was rapidly accumulated within 1 hr and largely cleared from the ovary at 24 hr. These results show the potential for imaging of endocrine target tissues by hormone-receptor binding, and the possibility of quantitation of hormone receptors in tissues under pathological conditions."}
{"id": "PMID:231649", "title": "Tumorgenicity of herpesvirus hominis type 2-transformed cells (line 333-8-9) in adult hamsters.", "content": "Inoculation of adult hamsters with greater than 1.5 X 10(2) Herpesvirus type 2 (HSV-2) transformed hamster embryo fibroblasts induced rapidly growing tumours at the site of inoculation, in more than 50 per cent of animals. The tumours were examined by light and electron microscopy, and were histologically anaplastic fibrosarcomas. Lung metastases were frequently found in tumour-bearing animals; these were usually only seen microscopically, and were cytologically similar to the primary tumours. The nature of tumour development showed similarities with naturally occurring tumours of man, and HSV-2 tumour is probably a better model of human cancer than other virus-induced tumours studied in the past.", "contents": "Tumorgenicity of herpesvirus hominis type 2-transformed cells (line 333-8-9) in adult hamsters. Inoculation of adult hamsters with greater than 1.5 X 10(2) Herpesvirus type 2 (HSV-2) transformed hamster embryo fibroblasts induced rapidly growing tumours at the site of inoculation, in more than 50 per cent of animals. The tumours were examined by light and electron microscopy, and were histologically anaplastic fibrosarcomas. Lung metastases were frequently found in tumour-bearing animals; these were usually only seen microscopically, and were cytologically similar to the primary tumours. The nature of tumour development showed similarities with naturally occurring tumours of man, and HSV-2 tumour is probably a better model of human cancer than other virus-induced tumours studied in the past."}
{"id": "PMID:231651", "title": "Input-output relations in the pathway of recurrent inhibition to motoneurones in the cat.", "content": "1. The output from Renshaw cells caused by a phasic motor volley was investigated when these neurones were submitted to a background firing secondary to a tonic motor discharge elicited by a repetitive stimulation of muscle group I afferents. It was invariably found in individual Renshaw cells that tonic excitation produced an increase in the additional ouput caused by the phasic motor volley. The curves displaying this increase exhibited a significant 'jump' when the output resulting from the combined tonic and phasic motor discharges ranged between 2 and 5 spikes during the first 10 msec following the phasic volley. 2. The whole pool of Renshaw cells was also considered by assessing the amount of recurrent inhibition in motoneurones following a phasic motor volley. Similarly it was found that additional recurrent inhibition elicited by a phasic motor volley was enhanced when the Renshaw cells received a tonic excitatory input. 3. The Renshaw cell discharges elicited by stimulation of two different nerves were compared when a conditioning stimulus was previously applied to only one of them. The results strongly suggest that a preceding volley caused a decrease in synaptic efficacy at the terminals of the recurrent collaterals. 4. The firing produced by current injected through the recording micro-electrode was investigated in one intracellularly recorded Renshaw cell. It was found that the current-frequency curve was linear for 'steady-state' firing but displayed a clearcut sigmoid shape for the earliest intervals before the final adaptation. 5. It is demonstrated that this sigmoid input-output relation in individual Renshaw cells is sufficient to explain how the controls acting on these neurones may change the gain in the recurrent pathway when Renshaw cells are fired by a phasic motor discharge. When Renshaw cells are fired by a longlasting tonic motor discharge the linear input-output relation in individual cells should not cause any modifications of the gain in the recurrent pathway. A change in this gain secondary to the effects of segmental and supraspinal control systems is, however, possible if the motor discharge creates a subliminal fringe within the pool of Renshaw cells.", "contents": "Input-output relations in the pathway of recurrent inhibition to motoneurones in the cat. 1. The output from Renshaw cells caused by a phasic motor volley was investigated when these neurones were submitted to a background firing secondary to a tonic motor discharge elicited by a repetitive stimulation of muscle group I afferents. It was invariably found in individual Renshaw cells that tonic excitation produced an increase in the additional ouput caused by the phasic motor volley. The curves displaying this increase exhibited a significant 'jump' when the output resulting from the combined tonic and phasic motor discharges ranged between 2 and 5 spikes during the first 10 msec following the phasic volley. 2. The whole pool of Renshaw cells was also considered by assessing the amount of recurrent inhibition in motoneurones following a phasic motor volley. Similarly it was found that additional recurrent inhibition elicited by a phasic motor volley was enhanced when the Renshaw cells received a tonic excitatory input. 3. The Renshaw cell discharges elicited by stimulation of two different nerves were compared when a conditioning stimulus was previously applied to only one of them. The results strongly suggest that a preceding volley caused a decrease in synaptic efficacy at the terminals of the recurrent collaterals. 4. The firing produced by current injected through the recording micro-electrode was investigated in one intracellularly recorded Renshaw cell. It was found that the current-frequency curve was linear for 'steady-state' firing but displayed a clearcut sigmoid shape for the earliest intervals before the final adaptation. 5. It is demonstrated that this sigmoid input-output relation in individual Renshaw cells is sufficient to explain how the controls acting on these neurones may change the gain in the recurrent pathway when Renshaw cells are fired by a phasic motor discharge. When Renshaw cells are fired by a longlasting tonic motor discharge the linear input-output relation in individual cells should not cause any modifications of the gain in the recurrent pathway. A change in this gain secondary to the effects of segmental and supraspinal control systems is, however, possible if the motor discharge creates a subliminal fringe within the pool of Renshaw cells."}
{"id": "PMID:231652", "title": "An electrophysiological analysis of the actions of prostaglandin on neuromuscular transmission in the guinea-pig vas deferens.", "content": "Effects of prostaglandins (PGs) on the neuromuscular junction of the guinea-pig vas deferens were investigated by the micro-electrode and double sucrose gap methods. 1. PGE1, PGE2 or PGF2 alpha (10(-10) to 10(-7) g/ml.) did not change the membrane potential, membrane resistance and electrical threshold required to produce the action potential. 2. PGs markedly suppressed the amplitude of excitatory junction potential (e.j.p.) but the facilitation phenomena seen with repetitive stimulation were not affected. PGs did not change the amplitude and frequency of the miniature e.j.p. 3. The action potential recorded from the small nerve bundle with the aid of an extracellular micro-electrode method was not affected by PGS. 4. The amplitude of the e.j.p. was dependent on the external concentration of Ca. When plotted against [Ca]o on a double log scale, the above relation yielded a straight line with a slope of 1.0. Application of PGs resulted in a parallel shift of this relation to the right. 5. From the concentrations of [Ca]o to produce a given e.j.p. in the absence and presence of various concentrations of PGE1, the linear relation was observed from double logarithmic plot between [[Ca]o ratio -1] and [PGE1]o. However the slope of the line was too small (-0.37) to indicate a simple competition between [PGE1]o and [Ca]o. 6. Indomethacin (10(-6) g/ml.) had no effect on the amplitudes of e.j.p. produced by repetitive stimulation. 7. These results indicate that a low concentration of PGs interact with [Ca]o at the activated nerve terminals, but that there is no modification of the actions of Ca in the nerve terminals required for release of chemical transmitter.", "contents": "An electrophysiological analysis of the actions of prostaglandin on neuromuscular transmission in the guinea-pig vas deferens. Effects of prostaglandins (PGs) on the neuromuscular junction of the guinea-pig vas deferens were investigated by the micro-electrode and double sucrose gap methods. 1. PGE1, PGE2 or PGF2 alpha (10(-10) to 10(-7) g/ml.) did not change the membrane potential, membrane resistance and electrical threshold required to produce the action potential. 2. PGs markedly suppressed the amplitude of excitatory junction potential (e.j.p.) but the facilitation phenomena seen with repetitive stimulation were not affected. PGs did not change the amplitude and frequency of the miniature e.j.p. 3. The action potential recorded from the small nerve bundle with the aid of an extracellular micro-electrode method was not affected by PGS. 4. The amplitude of the e.j.p. was dependent on the external concentration of Ca. When plotted against [Ca]o on a double log scale, the above relation yielded a straight line with a slope of 1.0. Application of PGs resulted in a parallel shift of this relation to the right. 5. From the concentrations of [Ca]o to produce a given e.j.p. in the absence and presence of various concentrations of PGE1, the linear relation was observed from double logarithmic plot between [[Ca]o ratio -1] and [PGE1]o. However the slope of the line was too small (-0.37) to indicate a simple competition between [PGE1]o and [Ca]o. 6. Indomethacin (10(-6) g/ml.) had no effect on the amplitudes of e.j.p. produced by repetitive stimulation. 7. These results indicate that a low concentration of PGs interact with [Ca]o at the activated nerve terminals, but that there is no modification of the actions of Ca in the nerve terminals required for release of chemical transmitter."}
{"id": "PMID:231654", "title": "Synthesis and biological properties of 2-, 5-, and 6-fluoronorepinephrines.", "content": "2-Fluoro-, 5-fluoro- and 6-fluorodimethoxybenzaldehydes were prepared by photochemical decomposition of the corresponding diazonium fluoroborates. The aldehydes were converted to the cyanohydrin trimethylsilyl ethers, which, in turn, were reduced to the dimethoxyphenethanolamines. Boron tribromide demethylation afforded the racemic ring-fluorinated norepinephrines. An alternate route, using the dibenzyloxyfluoroaldehyde, was also used to prepare 6-fluoronorepinephrine. The fluorine substituent markedly increases the phenolic acidities of these analogues. The biological properties conferred upon norepinephrine by the fluorine substituents in peripheral and central adrenergically responsive systems clearly demonstrate that 2-fluoronorepinephrine is a nearly a pure beta-adrenergic agonist, while 6-fluoronorepinephrine is an alpha-adrenergic agonist. 5-Fluoronorepinephrine retains both beta- and alpha-adrenergic agonist properties. Receptor-binding studies with specific radiolabeled ligands indicate that the specificity conferred by the site of fluorine substituents results from a change in the affinity of these analogues for the alpha- and beta-adrenergic receptors.", "contents": "Synthesis and biological properties of 2-, 5-, and 6-fluoronorepinephrines. 2-Fluoro-, 5-fluoro- and 6-fluorodimethoxybenzaldehydes were prepared by photochemical decomposition of the corresponding diazonium fluoroborates. The aldehydes were converted to the cyanohydrin trimethylsilyl ethers, which, in turn, were reduced to the dimethoxyphenethanolamines. Boron tribromide demethylation afforded the racemic ring-fluorinated norepinephrines. An alternate route, using the dibenzyloxyfluoroaldehyde, was also used to prepare 6-fluoronorepinephrine. The fluorine substituent markedly increases the phenolic acidities of these analogues. The biological properties conferred upon norepinephrine by the fluorine substituents in peripheral and central adrenergically responsive systems clearly demonstrate that 2-fluoronorepinephrine is a nearly a pure beta-adrenergic agonist, while 6-fluoronorepinephrine is an alpha-adrenergic agonist. 5-Fluoronorepinephrine retains both beta- and alpha-adrenergic agonist properties. Receptor-binding studies with specific radiolabeled ligands indicate that the specificity conferred by the site of fluorine substituents results from a change in the affinity of these analogues for the alpha- and beta-adrenergic receptors."}
{"id": "PMID:231656", "title": "Derivatives of 1,3-disubstituted 2,4(1H,3H)-quinazolinediones as possible peripheral vasodilators or antihypertensive agents.", "content": "A series of 1,3-disubstituted 2,4(1H,3H)-quinazolinediones was prepared from the 3-substituted 2,4(1H,3H)-quinazolinediones by treatment with sodium hydride and the desired alkyl halide in xylene. These compounds showed varying degrees of vasodilation and antihypertensive activity without significant blockade of alpha-adrenergic receptors. 1-[3-(N,N-Dimethylamino)propyl]-3-[3-(4-phenyl1-piperazinyl)propyl]-2,4(1H,3H)-quinazolinedione, which was selected for further studies, was more potent than papaverine in inducing vasodilation and induced a prolonged decrease in systolic blood pressure of hypertensive rats upon oral administration.", "contents": "Derivatives of 1,3-disubstituted 2,4(1H,3H)-quinazolinediones as possible peripheral vasodilators or antihypertensive agents. A series of 1,3-disubstituted 2,4(1H,3H)-quinazolinediones was prepared from the 3-substituted 2,4(1H,3H)-quinazolinediones by treatment with sodium hydride and the desired alkyl halide in xylene. These compounds showed varying degrees of vasodilation and antihypertensive activity without significant blockade of alpha-adrenergic receptors. 1-[3-(N,N-Dimethylamino)propyl]-3-[3-(4-phenyl1-piperazinyl)propyl]-2,4(1H,3H)-quinazolinedione, which was selected for further studies, was more potent than papaverine in inducing vasodilation and induced a prolonged decrease in systolic blood pressure of hypertensive rats upon oral administration."}
{"id": "PMID:231657", "title": "Mitochondrial antibodies--heterogeneity and effects on mitochondrial respiration.", "content": "Sera containing antimitochondrial antibodies (MTA) were tested for binding to intact mitochondria, sonic fragments (SMP), Complex I + III and to oligomycin sensitive ATPase (OS-ATPase) from bovine heart by indirect immunofluorescence. Antigens capable of binding to MTA were present in mitochondria and its fragments tested. Maximum binding was observed with SMP. It appears that one or more antigen binding sites are present on the matrix side of the inner mitochondrial membrane or some location exterior to the inner membrane. Normal human serum or sera containing MTA did not effect the respiration of intact mitochondria or sonic particles. However, NADH-cytochrome c reductase activity of complex I + III was enhanced by 10-60% by sera containing MTA antibodies.", "contents": "Mitochondrial antibodies--heterogeneity and effects on mitochondrial respiration. Sera containing antimitochondrial antibodies (MTA) were tested for binding to intact mitochondria, sonic fragments (SMP), Complex I + III and to oligomycin sensitive ATPase (OS-ATPase) from bovine heart by indirect immunofluorescence. Antigens capable of binding to MTA were present in mitochondria and its fragments tested. Maximum binding was observed with SMP. It appears that one or more antigen binding sites are present on the matrix side of the inner mitochondrial membrane or some location exterior to the inner membrane. Normal human serum or sera containing MTA did not effect the respiration of intact mitochondria or sonic particles. However, NADH-cytochrome c reductase activity of complex I + III was enhanced by 10-60% by sera containing MTA antibodies."}
{"id": "PMID:231658", "title": "Isolation and characterization of a new simian foamy virus serotype from lymphocytes of a Papio cynocephalus baboon.", "content": "A new type of syncytium-forming (foamy) virus was isolated from peripheral lymphocytes of a Papio cynocephalus baboon after cocultivation with a rhesus monkey cell line. The isolate was characterized by cytopathogenic effect, host range, electron microscopy, reverse transcriptase activity and physical and chemical properties. Seroneutralization tests indicate that the new isolate is antigenically distinct from the other nine known simian foamy virus serotypes.", "contents": "Isolation and characterization of a new simian foamy virus serotype from lymphocytes of a Papio cynocephalus baboon. A new type of syncytium-forming (foamy) virus was isolated from peripheral lymphocytes of a Papio cynocephalus baboon after cocultivation with a rhesus monkey cell line. The isolate was characterized by cytopathogenic effect, host range, electron microscopy, reverse transcriptase activity and physical and chemical properties. Seroneutralization tests indicate that the new isolate is antigenically distinct from the other nine known simian foamy virus serotypes."}
{"id": "PMID:231659", "title": "Studies on lithium transport across the red cell membrane. VI. Properties of a sulfhydryl group involved in ouabain-resistant Na+-Li+ (and Na+-Na+) exchange in human and bovine erythrocytes.", "content": "The reactivity of the SH-group essential for ouabain-resistant Na+-Li+ (and Na+-Na+) exchange and its location within the membrane are studied on human and beef erythrocytes and beef red cell ghosts. N-ethylmaleimide (NEM), 1,6-hexane dimaleimide, and iodoacetamide can induce an irreversible, partial inhibition of Na+-Li+ exchange in erythrocytes of the two species. The development of the inhibition due to the alkylating agents is greatly accelerated by external Na+ and Li+. The inhibition takes 3 min (NEM) and 60 min (iodoacetamide) to come to completion in isotonic Na+ media, but is hardly detectable in choline+, K+ or Mg2+ media. The transport site of the exchange system and the site promoting NEM binding exhibit similar affinities for external Na+. The impermeable, monofunctional glutathione derivative of 1,6-hexane dimaleimide does not inhibit Na+-Li+ exchange. The mercurials PCMBS, PCMB, and Hg2+ inhibit Na+-Li+ exchange in beef, but not in human erythrocytes. The inhibitory action of PCMBS, being slightly accelerated by external Na+, is fully reversed by penetrating thiols such as 2-mercaptoethanol, whilst glutathione, an impermeable thiol, is ineffective. Pretreatment with PCMBS affords partial protection from the irreversible inhibition caused by NEM. Oxidation with copper orthophenanthroline inhibits Na+-Li+ exchange only when performed in the presence of penetrating thiols such as 2-mercaptoethanol. It is concluded that the SH-reagents studied inhibit Na+-Li+ exchange by modifying an essential SH-group of a membrane protein in such a way that the turnover number of the exchange system is reduced. This SH-group is separated from both the red cell exterior and interior by a penetration barrier and seems to be distinct from the cation binding site. The action of external Na+ and Li+ in promoting the reaction of alkylating inhibitors is interpreted to result from a conformational change of the transport protein induced by the binding of external Na+ or Li+.", "contents": "Studies on lithium transport across the red cell membrane. VI. Properties of a sulfhydryl group involved in ouabain-resistant Na+-Li+ (and Na+-Na+) exchange in human and bovine erythrocytes. The reactivity of the SH-group essential for ouabain-resistant Na+-Li+ (and Na+-Na+) exchange and its location within the membrane are studied on human and beef erythrocytes and beef red cell ghosts. N-ethylmaleimide (NEM), 1,6-hexane dimaleimide, and iodoacetamide can induce an irreversible, partial inhibition of Na+-Li+ exchange in erythrocytes of the two species. The development of the inhibition due to the alkylating agents is greatly accelerated by external Na+ and Li+. The inhibition takes 3 min (NEM) and 60 min (iodoacetamide) to come to completion in isotonic Na+ media, but is hardly detectable in choline+, K+ or Mg2+ media. The transport site of the exchange system and the site promoting NEM binding exhibit similar affinities for external Na+. The impermeable, monofunctional glutathione derivative of 1,6-hexane dimaleimide does not inhibit Na+-Li+ exchange. The mercurials PCMBS, PCMB, and Hg2+ inhibit Na+-Li+ exchange in beef, but not in human erythrocytes. The inhibitory action of PCMBS, being slightly accelerated by external Na+, is fully reversed by penetrating thiols such as 2-mercaptoethanol, whilst glutathione, an impermeable thiol, is ineffective. Pretreatment with PCMBS affords partial protection from the irreversible inhibition caused by NEM. Oxidation with copper orthophenanthroline inhibits Na+-Li+ exchange only when performed in the presence of penetrating thiols such as 2-mercaptoethanol. It is concluded that the SH-reagents studied inhibit Na+-Li+ exchange by modifying an essential SH-group of a membrane protein in such a way that the turnover number of the exchange system is reduced. This SH-group is separated from both the red cell exterior and interior by a penetration barrier and seems to be distinct from the cation binding site. The action of external Na+ and Li+ in promoting the reaction of alkylating inhibitors is interpreted to result from a conformational change of the transport protein induced by the binding of external Na+ or Li+."}
{"id": "PMID:231686", "title": "An improved method for estimating sequence divergence between related DNAs from changes in restriction endonuclease cleavage sites.", "content": "We have developed a theory to estimate the degree of sequence divergence between related DNAs from the comparison of restriction endonuclease recognition sites. Two major improvements have been made upon a similar method reported by Upholt (1977). First, the most probable value is calculated by the collective use of all available data. This reduces intrinsic statistical error and extends the analyzable range of sequence divergence. Second, all variables are redefined so that they have strict mathematical implications. This corrects a serious error arising from the misinterpretation of the meaning of the fraction of conserved cleavage sites. With this refined method, sequence divergence between rat and mouse mitochondrial DNAs (mtDNAs) was calculated to be about 25% substitutions/nucleotide, which is in good agreement with the DNA-DNA hybridization data obtained by Jakovcic et al. (1975). It was also estimated that the three types of rat mtDNAs differ from one another by 0.3 approximately 1% of total base pairs. These values are 2 approximately 5 times smaller than those obtained with the conventional method.", "contents": "An improved method for estimating sequence divergence between related DNAs from changes in restriction endonuclease cleavage sites. We have developed a theory to estimate the degree of sequence divergence between related DNAs from the comparison of restriction endonuclease recognition sites. Two major improvements have been made upon a similar method reported by Upholt (1977). First, the most probable value is calculated by the collective use of all available data. This reduces intrinsic statistical error and extends the analyzable range of sequence divergence. Second, all variables are redefined so that they have strict mathematical implications. This corrects a serious error arising from the misinterpretation of the meaning of the fraction of conserved cleavage sites. With this refined method, sequence divergence between rat and mouse mitochondrial DNAs (mtDNAs) was calculated to be about 25% substitutions/nucleotide, which is in good agreement with the DNA-DNA hybridization data obtained by Jakovcic et al. (1975). It was also estimated that the three types of rat mtDNAs differ from one another by 0.3 approximately 1% of total base pairs. These values are 2 approximately 5 times smaller than those obtained with the conventional method."}
{"id": "PMID:231687", "title": "Trophoblastic neoplasia in an African urban population.", "content": "A clinical study of trophoblastic neoplasia in a Nigerian population in Lagos over a four-year period is reported. A high incidence of one in 379 deliveries for benign trophoblastic tumor and one in 846 deliveries for malignant tumor was found. Seventeen percent of benign trophoblastic tumors in this series progressed to the malignant type, but malignant trophoblastic tumor was preceded by the benign type (hydatidiform mole) in 46 percent of cases. The anterior vaginal wall is a common site for metastases of malignant trophoblastic neoplasia and, in one patient, the lesion progressed further to form a vesicovaginal fistula. While the management of benign disease was conservative, all cases of malignant trophoblastic neoplasia received chemotherapy.", "contents": "Trophoblastic neoplasia in an African urban population. A clinical study of trophoblastic neoplasia in a Nigerian population in Lagos over a four-year period is reported. A high incidence of one in 379 deliveries for benign trophoblastic tumor and one in 846 deliveries for malignant tumor was found. Seventeen percent of benign trophoblastic tumors in this series progressed to the malignant type, but malignant trophoblastic tumor was preceded by the benign type (hydatidiform mole) in 46 percent of cases. The anterior vaginal wall is a common site for metastases of malignant trophoblastic neoplasia and, in one patient, the lesion progressed further to form a vesicovaginal fistula. While the management of benign disease was conservative, all cases of malignant trophoblastic neoplasia received chemotherapy."}
{"id": "PMID:231698", "title": "Effect of linoleic acid hydroperoxide on liver microsomal enzymes in vitro.", "content": "Rat liver microsomes incubated with linoleic acid hydroperoxide (LAHPO) lost cytochrome P-450 specifically among the enzymes of microsomal electron transport systems. The loss of cytochrome P-450 content and glucose-6-phosphatase activity by LAHPO was accompanied by an increase in malondialdehyde (MDA) production. Turbidity of microsomal suspensions was decreased with increasing MDA production, but not proportionately. Diethyldithiocarbamate (DTC), N,N'-diphenyl-p-phenylenediamine and alpha-tocopherol inhibited almost completely the LAHPO-induced MDA production of microsomes, however no perfect protection against the loss of cytochrome P-450 content and glucose-6-phosphatase activity was observed. The decrease of microsomal turbidity by LAHPO was little affected in the presence of DTC. Purified cytochrome P-450 was destroyed by LAHPO, with minimal protection by the compounds described above. These results suggest the possibility that the loss of microsomal enzyme activities during lipid peroxidation may be attributed largely to a direct attack on enzyme proteins by lipid peroxides rather than indirectly to a structural damage of microsomal membranes resulting from peroxidative breakdown of membrane lipids.", "contents": "Effect of linoleic acid hydroperoxide on liver microsomal enzymes in vitro. Rat liver microsomes incubated with linoleic acid hydroperoxide (LAHPO) lost cytochrome P-450 specifically among the enzymes of microsomal electron transport systems. The loss of cytochrome P-450 content and glucose-6-phosphatase activity by LAHPO was accompanied by an increase in malondialdehyde (MDA) production. Turbidity of microsomal suspensions was decreased with increasing MDA production, but not proportionately. Diethyldithiocarbamate (DTC), N,N'-diphenyl-p-phenylenediamine and alpha-tocopherol inhibited almost completely the LAHPO-induced MDA production of microsomes, however no perfect protection against the loss of cytochrome P-450 content and glucose-6-phosphatase activity was observed. The decrease of microsomal turbidity by LAHPO was little affected in the presence of DTC. Purified cytochrome P-450 was destroyed by LAHPO, with minimal protection by the compounds described above. These results suggest the possibility that the loss of microsomal enzyme activities during lipid peroxidation may be attributed largely to a direct attack on enzyme proteins by lipid peroxides rather than indirectly to a structural damage of microsomal membranes resulting from peroxidative breakdown of membrane lipids."}
{"id": "PMID:231699", "title": "Radioimmunoassay of methionine enkephalin and interference by brain factor of immunoreactivity and opiate receptor binding activity.", "content": "We developed a radioimmunoassay of methionine-enkephalin (met-enk) which was found to be highly specific to the peptide and 1 pmol was the detection limit. Interference by the following peptides was practically negligible; leucine-enkephalin, LAP- or CNBr-treated met-end, alpha- and beta-endorphins. Morphine and its congeners were totally inert. Measurement of met-enk in rat brain P2 fraction revealed besides met-enk, the presence of the factor which cross-reacted with the antiserum and also appeared to bind with the brain opiate receptor. Though the nature of the factor has not yet been characterized, it is suggested that for qualitative assessment of the tissue level of met-enk, a method to selectively inactivate either the peptide or the factor should be developed first.", "contents": "Radioimmunoassay of methionine enkephalin and interference by brain factor of immunoreactivity and opiate receptor binding activity. We developed a radioimmunoassay of methionine-enkephalin (met-enk) which was found to be highly specific to the peptide and 1 pmol was the detection limit. Interference by the following peptides was practically negligible; leucine-enkephalin, LAP- or CNBr-treated met-end, alpha- and beta-endorphins. Morphine and its congeners were totally inert. Measurement of met-enk in rat brain P2 fraction revealed besides met-enk, the presence of the factor which cross-reacted with the antiserum and also appeared to bind with the brain opiate receptor. Though the nature of the factor has not yet been characterized, it is suggested that for qualitative assessment of the tissue level of met-enk, a method to selectively inactivate either the peptide or the factor should be developed first."}
{"id": "PMID:231700", "title": "Effects of chronic treatment with captopril (SQ 14,225), an orally active inhibitor of angiotensin I-converting enzyme, in spontaneously hypertensive rats.", "content": "The effects of hydralazine (3 mg/kg) and the angiotensin I-converting enzyme (ACE) inhibitor captopril (SQ 14,225) (100 mg/kg) on mean arterial blood pressure, plasma renin activity, urinary volume and urinary Na+,K+, and aldosterone concentrations were examined in spontaneously hypertensive rats of the Okamoto and Aoki strain (SHR) after oral daily dosing for 2 weeks, 3 or 6 months. Captopril caused progressive cumulative reductions in blood pressure resulting in normalization of pressure after 6 months of dosing. Hydralazine also significantly reduced blood pressure but not to the level of normotensive rats of the Wistar-Kyoto strain (WKY). Reductions in heart size paralleled the changes in blood pressure, normalization of cardiac hypertrophy occurring after captopril but not hydralazine. Plasma renin activity increased approximately 2-3 fold after hydralazine and 15-fold after captopril. Neither hydralazine nor captopril had any consistent effects on 24-hr urine volume, urinary Na+,K+ or aldosterone excretion. These results indicate that chronic inhibition of ACE with captopril induces normalization of blood pressure in SHR, a normal-renin model of hypertension.", "contents": "Effects of chronic treatment with captopril (SQ 14,225), an orally active inhibitor of angiotensin I-converting enzyme, in spontaneously hypertensive rats. The effects of hydralazine (3 mg/kg) and the angiotensin I-converting enzyme (ACE) inhibitor captopril (SQ 14,225) (100 mg/kg) on mean arterial blood pressure, plasma renin activity, urinary volume and urinary Na+,K+, and aldosterone concentrations were examined in spontaneously hypertensive rats of the Okamoto and Aoki strain (SHR) after oral daily dosing for 2 weeks, 3 or 6 months. Captopril caused progressive cumulative reductions in blood pressure resulting in normalization of pressure after 6 months of dosing. Hydralazine also significantly reduced blood pressure but not to the level of normotensive rats of the Wistar-Kyoto strain (WKY). Reductions in heart size paralleled the changes in blood pressure, normalization of cardiac hypertrophy occurring after captopril but not hydralazine. Plasma renin activity increased approximately 2-3 fold after hydralazine and 15-fold after captopril. Neither hydralazine nor captopril had any consistent effects on 24-hr urine volume, urinary Na+,K+ or aldosterone excretion. These results indicate that chronic inhibition of ACE with captopril induces normalization of blood pressure in SHR, a normal-renin model of hypertension."}
{"id": "PMID:231701", "title": "Failure of dibutyryl and 8-bromo-cyclic GMP to mimic the antagonistic action of carbachol on the positive inotropic effects of sympathomimetic amines in the canine isolated ventricular myocardium.", "content": "Effects of carbachol, dbcGMP and 8-bromo-cyclic GMP on the positive inotropic actions of sympathomimetic amines and dbcAMP were studied on the canine isolated right ventricular myocardium. Carbachol alone did not substantially change the developed tension of the muscle, but did markedly shift the dose response curve for isoprenaline on the developed tension to the right and depressed the maximal response to the drug in a concentration dependent manner. The positive inotropic action of phenylephrine was affected by carbachol in the same manner as that of isoprenaline. DbcGMP in concentrations of 10(-3) M and higher produced a significant increase in the developed tension. The positive inotropic action of dbcGMP was partly inhibited by a beta-adrenoceptor blocking agent, pindolol. In the presence of dbcGMP, isoprenaline produced an action similar to that seen in the control experiment, but this action was not maintained on such a steady state level as in the control. This rapid decline of the effect of isoprenaline in the presence of dbcGMP was prevented by adding ascorbic acid to the organ bath. The positive inotropic actions of phenylephrine and of dbcAMP were not substantially affected by dbcGMP. 8-Bromo-cyclic GMP in a concentration of 10(-4) M did not change either the basal developed tension or the positive inotropic actions of noradrenaline and of isoprenaline. The present results indicate that these cyclic GMP derivatives are not able to mimic the antagonistic action of cholinergic stimulation on the positive inotropic action of adrenergic stimulation on the positive inotropic action of adrenergic stimulation on the canine ventricular myocardium.", "contents": "Failure of dibutyryl and 8-bromo-cyclic GMP to mimic the antagonistic action of carbachol on the positive inotropic effects of sympathomimetic amines in the canine isolated ventricular myocardium. Effects of carbachol, dbcGMP and 8-bromo-cyclic GMP on the positive inotropic actions of sympathomimetic amines and dbcAMP were studied on the canine isolated right ventricular myocardium. Carbachol alone did not substantially change the developed tension of the muscle, but did markedly shift the dose response curve for isoprenaline on the developed tension to the right and depressed the maximal response to the drug in a concentration dependent manner. The positive inotropic action of phenylephrine was affected by carbachol in the same manner as that of isoprenaline. DbcGMP in concentrations of 10(-3) M and higher produced a significant increase in the developed tension. The positive inotropic action of dbcGMP was partly inhibited by a beta-adrenoceptor blocking agent, pindolol. In the presence of dbcGMP, isoprenaline produced an action similar to that seen in the control experiment, but this action was not maintained on such a steady state level as in the control. This rapid decline of the effect of isoprenaline in the presence of dbcGMP was prevented by adding ascorbic acid to the organ bath. The positive inotropic actions of phenylephrine and of dbcAMP were not substantially affected by dbcGMP. 8-Bromo-cyclic GMP in a concentration of 10(-4) M did not change either the basal developed tension or the positive inotropic actions of noradrenaline and of isoprenaline. The present results indicate that these cyclic GMP derivatives are not able to mimic the antagonistic action of cholinergic stimulation on the positive inotropic action of adrenergic stimulation on the positive inotropic action of adrenergic stimulation on the canine ventricular myocardium."}
{"id": "PMID:231703", "title": "Effects of smooth muscle stimulants on 1-isoprenaline-beta-adrenoceptor interaction in taenia from guinea pig caecum.", "content": "An increase in intracellular cyclic AMP levels induced by 1-isoprenaline (1-Iso) was significantly depressed in coexistence with BuTMA or histamine, but not with KCl or BaCl2. An analysis of steady state data for d,1-[3H]-isoprenaline binding to single cells of taenia from guinea pig caecum in the presence of histamine or KCl by Scatchard plots was performed. The affinity for 1-Iso for beta-adrenoceptor sites was decreased in the presence of histamine but not in the presence of KCl. These results suggest that the interaction of 1-Iso with the beta-adrenoceptors is interfered with by histamine and butyltrimethylammonium, for which the specific receptors were postulated, but not with KCl and BaCl2, nonspecific smooth muscle stimulants. These phenomena demonstrate the heterotropic negative cooperatively among the heterogeneous receptors.", "contents": "Effects of smooth muscle stimulants on 1-isoprenaline-beta-adrenoceptor interaction in taenia from guinea pig caecum. An increase in intracellular cyclic AMP levels induced by 1-isoprenaline (1-Iso) was significantly depressed in coexistence with BuTMA or histamine, but not with KCl or BaCl2. An analysis of steady state data for d,1-[3H]-isoprenaline binding to single cells of taenia from guinea pig caecum in the presence of histamine or KCl by Scatchard plots was performed. The affinity for 1-Iso for beta-adrenoceptor sites was decreased in the presence of histamine but not in the presence of KCl. These results suggest that the interaction of 1-Iso with the beta-adrenoceptors is interfered with by histamine and butyltrimethylammonium, for which the specific receptors were postulated, but not with KCl and BaCl2, nonspecific smooth muscle stimulants. These phenomena demonstrate the heterotropic negative cooperatively among the heterogeneous receptors."}
{"id": "PMID:231704", "title": "Effect of colchicine on steroid secretion from rat adrenal gland.", "content": "To determine the influence of colchicine on adrenocortical function in vivo, we gave significant amounts subcutaneously to rats and observed the distribution to the anterior pituitary and adrenal glands. Corticosteroids in the serum and adrenal gland were increased remarkably by the administration of colchicine in a dose-dependent manner. Maximum elevation was achieved around 2.5 hours after the injection and continued for at least 4 hours. Maximum levels produced by the injection of 0.1 U/rat of adrenocorticotropic hormone, the latter producing temporary increases in corticosteroids in the serum and adrenal gland. A significant augmentation of corticosteroids in the serum and adrenal gland resulted when colchicine was administered 60 minutes prior to the injection of adrenocorticotropic hormone. The pattern of intracellular distribution of corticosteroids in the adrenal glands of rats given colchicine was the same as that seen in rats given adrenocorticotropic hormone. In the in vitro experiment, only high concentrations of colchicine such as 10(-3) M added to the incubation system of the adrenal quarters suppressed the release of corticosteroids from the adrenal gland. Thus, the continuous stimulation of the synthesis and secretion of adrenocortical hormone seen with the administration of colchicine may explain why this drug is effective in the treatment of gouty arthritis.", "contents": "Effect of colchicine on steroid secretion from rat adrenal gland. To determine the influence of colchicine on adrenocortical function in vivo, we gave significant amounts subcutaneously to rats and observed the distribution to the anterior pituitary and adrenal glands. Corticosteroids in the serum and adrenal gland were increased remarkably by the administration of colchicine in a dose-dependent manner. Maximum elevation was achieved around 2.5 hours after the injection and continued for at least 4 hours. Maximum levels produced by the injection of 0.1 U/rat of adrenocorticotropic hormone, the latter producing temporary increases in corticosteroids in the serum and adrenal gland. A significant augmentation of corticosteroids in the serum and adrenal gland resulted when colchicine was administered 60 minutes prior to the injection of adrenocorticotropic hormone. The pattern of intracellular distribution of corticosteroids in the adrenal glands of rats given colchicine was the same as that seen in rats given adrenocorticotropic hormone. In the in vitro experiment, only high concentrations of colchicine such as 10(-3) M added to the incubation system of the adrenal quarters suppressed the release of corticosteroids from the adrenal gland. Thus, the continuous stimulation of the synthesis and secretion of adrenocortical hormone seen with the administration of colchicine may explain why this drug is effective in the treatment of gouty arthritis."}
{"id": "PMID:231716", "title": "[Significance of virus-specific antibodies to EBV-antigens in patients with nasopharyngeal carcinoma (author's transl)].", "content": "Sera collected from patients with nasopharyngeal carcinoma, patients with other head and neck neoplasms, patients with infectious mononucleosis (IM), and healthy donors were titrated for antibodies (IgM, IgG, IgA) against Epstein-Barr-Virus (EBV) specific antigens (VCA, EA, EBNA) by indirect and by antikomplementary immunfluorescence. NPC-patients develop significantly high anti-EBV titers of IgG and IgA. In contrast patients with neoplasms (mainly carcinomas) arising in sites of the head and neck other than the nasopharynx revealed a lower incidence of high titers. Our results emphasize the remarkable predominance of IgA-antibodies to VCA and EA in NPC-patients and shows that Europeans to not differ in that respect from Asian patients. The significance and implications of these findings are discussed.", "contents": "[Significance of virus-specific antibodies to EBV-antigens in patients with nasopharyngeal carcinoma (author's transl)]. Sera collected from patients with nasopharyngeal carcinoma, patients with other head and neck neoplasms, patients with infectious mononucleosis (IM), and healthy donors were titrated for antibodies (IgM, IgG, IgA) against Epstein-Barr-Virus (EBV) specific antigens (VCA, EA, EBNA) by indirect and by antikomplementary immunfluorescence. NPC-patients develop significantly high anti-EBV titers of IgG and IgA. In contrast patients with neoplasms (mainly carcinomas) arising in sites of the head and neck other than the nasopharynx revealed a lower incidence of high titers. Our results emphasize the remarkable predominance of IgA-antibodies to VCA and EA in NPC-patients and shows that Europeans to not differ in that respect from Asian patients. The significance and implications of these findings are discussed."}
{"id": "PMID:231724", "title": "Replication of the colicin E1 plasmid in extracts of Escherichia coli: uncoupling of leading strand from lagging strand synthesis.", "content": "The replication of the ColEl plasmid was studied in extracts from E. coli dnaG mutants. It was found that the synthesis of the complementary strands of ColEl DNA can be carried out in these extracts in two consecutive steps: (1) synthesis of the leading L strand independent of the dnaG function, and (2) synthesis of the lagging H strand depending upon addition of wild-type dnaG protein. In contrast to L strand synthesis, the latter reaction is insensitive to rifampicin and novobiocin. Both synthetic pathways are however blocked by antiserum directed against dnaB protein. This indicates an additional role of the dnaB protein in duplex DNA replication besides assisting the dnaG protein in the priming of lagging strand synthesis. The T7 gene-4 protein acting in conjunction with T7 DNA polymerase can substitute for both the function of the dnaB and dnaG protein. It is concluded that plasmid replication proceeds by a semi-discontinuous mechanism.", "contents": "Replication of the colicin E1 plasmid in extracts of Escherichia coli: uncoupling of leading strand from lagging strand synthesis. The replication of the ColEl plasmid was studied in extracts from E. coli dnaG mutants. It was found that the synthesis of the complementary strands of ColEl DNA can be carried out in these extracts in two consecutive steps: (1) synthesis of the leading L strand independent of the dnaG function, and (2) synthesis of the lagging H strand depending upon addition of wild-type dnaG protein. In contrast to L strand synthesis, the latter reaction is insensitive to rifampicin and novobiocin. Both synthetic pathways are however blocked by antiserum directed against dnaB protein. This indicates an additional role of the dnaB protein in duplex DNA replication besides assisting the dnaG protein in the priming of lagging strand synthesis. The T7 gene-4 protein acting in conjunction with T7 DNA polymerase can substitute for both the function of the dnaB and dnaG protein. It is concluded that plasmid replication proceeds by a semi-discontinuous mechanism."}
{"id": "PMID:231722", "title": "[Salmonellosis in children in Ivory Coast, (A study on 69 cases) (author's transl)].", "content": "Salmonellosis are still endemic in Ivory Coast. In 1975 they were responsible for 1,75 p. 100 of the admittances in the pediatric department of Treichville University Hospital. In children, the conventional distinction between major and minor salmonellosis is not always obvious. Interpretation of Widal sero-diagnosis is often difficult and awkward. Chloramphenicol generally leads to satisfactory evolution. Salmonellosis are still a problem for Public Health Service. Immunization, is the only effective prophylaxis, but is not carried out yet in Ivory Coast.", "contents": "[Salmonellosis in children in Ivory Coast, (A study on 69 cases) (author's transl)]. Salmonellosis are still endemic in Ivory Coast. In 1975 they were responsible for 1,75 p. 100 of the admittances in the pediatric department of Treichville University Hospital. In children, the conventional distinction between major and minor salmonellosis is not always obvious. Interpretation of Widal sero-diagnosis is often difficult and awkward. Chloramphenicol generally leads to satisfactory evolution. Salmonellosis are still a problem for Public Health Service. Immunization, is the only effective prophylaxis, but is not carried out yet in Ivory Coast."}
{"id": "PMID:231725", "title": "In vitro insertion of the lambda attachment site into the plasmid RP4.", "content": "The region of the phage lambda chromosome containing the attachment site (P.P') and the genes int and xis, excised by the action of endonuclease R.EcoRI, has been inserted into the unique site for that enzyme on the promiscuous conjugative plasmid, RP4, generating the recombinant plasmid RP4att lambda. Transformants containing the hybrid plasmid were recognised by their ability to allow efficient lysogenization by phage lambda b2 (Weil and Signer, 1968; Echols et al., 1968) containing the mutant attachment site delta. P'. The construction and properties of the hybrid plasmid RP4att lambda are described.", "contents": "In vitro insertion of the lambda attachment site into the plasmid RP4. The region of the phage lambda chromosome containing the attachment site (P.P') and the genes int and xis, excised by the action of endonuclease R.EcoRI, has been inserted into the unique site for that enzyme on the promiscuous conjugative plasmid, RP4, generating the recombinant plasmid RP4att lambda. Transformants containing the hybrid plasmid were recognised by their ability to allow efficient lysogenization by phage lambda b2 (Weil and Signer, 1968; Echols et al., 1968) containing the mutant attachment site delta. P'. The construction and properties of the hybrid plasmid RP4att lambda are described."}
{"id": "PMID:231726", "title": "DNA supercoiling and transcription in Escherichia coli: influence of RNA polymerase mutations.", "content": "Coumermycin A1, a specific inhibitor of DNA gyrase, differentially changes the spectrum of proteins synthesized in wild type E. coli cells but has no effect on the protein spectrum in mutant cells with coumermycin-resistant DNA gyrase. The rpoB265 mutation affecting RNA polymerase decreases the coumermycin A1-sensitivity of bacteria while the rpoC3 mutation increases it. The interaction of wild type and mutant RpoB265 RNA polymerases with ColEl plasmid DNA in vitro is differently affected by DNA supercoiling. No such differences are observed in the case of RpoC3 RNA polymerase. The results suggest that template supercoiling may have a substantial effect on transcription in vivo, an effect which, in some cases, depends on the properties of RNA polymerase.", "contents": "DNA supercoiling and transcription in Escherichia coli: influence of RNA polymerase mutations. Coumermycin A1, a specific inhibitor of DNA gyrase, differentially changes the spectrum of proteins synthesized in wild type E. coli cells but has no effect on the protein spectrum in mutant cells with coumermycin-resistant DNA gyrase. The rpoB265 mutation affecting RNA polymerase decreases the coumermycin A1-sensitivity of bacteria while the rpoC3 mutation increases it. The interaction of wild type and mutant RpoB265 RNA polymerases with ColEl plasmid DNA in vitro is differently affected by DNA supercoiling. No such differences are observed in the case of RpoC3 RNA polymerase. The results suggest that template supercoiling may have a substantial effect on transcription in vivo, an effect which, in some cases, depends on the properties of RNA polymerase."}
{"id": "PMID:231727", "title": "A cleavage map of the TOL plasmid of Pseudomonas putida mt-2.", "content": "A cleavage map of the TOL plasmid pWWO has been determined for the restriction endonucleases HindIII and XhoI. A number of techniques were employed including (i) digestion of purified cleavage products with a second enzyme; (ii) hybridisation of purified XhoI fragments to Southern blots of HindIII digest products and (iii) analysis of a number of deletion mutants.", "contents": "A cleavage map of the TOL plasmid of Pseudomonas putida mt-2. A cleavage map of the TOL plasmid pWWO has been determined for the restriction endonucleases HindIII and XhoI. A number of techniques were employed including (i) digestion of purified cleavage products with a second enzyme; (ii) hybridisation of purified XhoI fragments to Southern blots of HindIII digest products and (iii) analysis of a number of deletion mutants."}
{"id": "PMID:231728", "title": "Absence of relationship between UV-induced reversion frequency and nucleotide sequence at the CYC1 locus of yeast.", "content": "The UV induced mutation frequency of a given base pair located at different sites within the CYC1 gene of Saccharomyces cerevisiae was found to vary by more than fifty fold, indicating the existence of hotspots and coldspots typical of those found in other organisms. We were unable, however, to find any feature of the nucleotide sequence at or near the sites of mutation that explains this variability. These and other data suggest that hotspots are not located within regions particularly susceptible to the formation of premutational lesions. More probably the variation in mutability depends on differences in the activity of enzymes responsible for producing mutations, though the reasons for these differences are not understood and may depend on factors not directly related to nucleotide sequence.", "contents": "Absence of relationship between UV-induced reversion frequency and nucleotide sequence at the CYC1 locus of yeast. The UV induced mutation frequency of a given base pair located at different sites within the CYC1 gene of Saccharomyces cerevisiae was found to vary by more than fifty fold, indicating the existence of hotspots and coldspots typical of those found in other organisms. We were unable, however, to find any feature of the nucleotide sequence at or near the sites of mutation that explains this variability. These and other data suggest that hotspots are not located within regions particularly susceptible to the formation of premutational lesions. More probably the variation in mutability depends on differences in the activity of enzymes responsible for producing mutations, though the reasons for these differences are not understood and may depend on factors not directly related to nucleotide sequence."}
{"id": "PMID:231729", "title": "A restriction enzyme cleavage map of Tn5 and location of a region encoding neomycin resistance.", "content": "This paper reports a cleavage site map of Tn5 for restriction enzymes BamHI, Bg/I, Bg/II, Hind II, HindIII, HpaI, Sa/I, Aval, SmaI, XhoI, PstI, PvuII, HaeII and HaeIII that was determined by the analysis of restriction enzyme cleavage patterns of ColEl, two independent ColEl::Tn5 plasmids, and a ColEl::Tn5 deletion derivative. Ba/I, EcoRI, KpnI, and PvuI do not cleave Tn5. Construction and analysis of in vitro-generated deletions of a ColEl::Tn5 plasmid limit the sequences encoding neomycin resistance to a 1500-base-pair-long segment of Tn5. Insertion of DNA at a Bg/II site within this segment results in loss of the neomycin resistance phenotype. Since this Bg/II site lies in an inverted repeat region, sequences within this repeat seem to be involved in the expression of neomycin resistance.", "contents": "A restriction enzyme cleavage map of Tn5 and location of a region encoding neomycin resistance. This paper reports a cleavage site map of Tn5 for restriction enzymes BamHI, Bg/I, Bg/II, Hind II, HindIII, HpaI, Sa/I, Aval, SmaI, XhoI, PstI, PvuII, HaeII and HaeIII that was determined by the analysis of restriction enzyme cleavage patterns of ColEl, two independent ColEl::Tn5 plasmids, and a ColEl::Tn5 deletion derivative. Ba/I, EcoRI, KpnI, and PvuI do not cleave Tn5. Construction and analysis of in vitro-generated deletions of a ColEl::Tn5 plasmid limit the sequences encoding neomycin resistance to a 1500-base-pair-long segment of Tn5. Insertion of DNA at a Bg/II site within this segment results in loss of the neomycin resistance phenotype. Since this Bg/II site lies in an inverted repeat region, sequences within this repeat seem to be involved in the expression of neomycin resistance."}
{"id": "PMID:231730", "title": "Reactivity of Paul-Bunnell type heterophile antibody in sera from infectious mononucleosis patients with the surface of lymphoid cells carrying Epstein-Barr virus genomes.", "content": "The possible presence of Paul-Bunnell (PB) antigen on Epstein-Barr virus (EBV)-transformed lymphocytes were investigated. Of 23 EBV genome-positive lymphoblastoid cell lines tested all but one absorbed PB type antibody from the serum of an infectious mononucleosis patient. The one EBV-negative B cell line tested did not absorb the heterophile antibody. PB antibody, purified by an immunoadsorbent procedure using beef cell antigen, reacted with the EBV producer P3HR-1 cell line in an indirect membrane immunofluorescence test and was shown to be IgM antibody. Titers of heterophile agglutinin and reactivity with the cell surface were reduced to the same degree by absorption with beef cell antigen but not with guinea pig kidney antigen. PB antibody was distinct from IgM antibody against the EBV-determined membrane antigen, since the latter was not absorbed by beef cell antigen. PB antibody was also reactive with other EBV-positive B cell lines (QIMR-WIL, NC-37, and Raji) which were free of surface IgM. No reaction occurred with the nonproducer P3HR-1 line, a null cell line, and two T cell lines. The results suggest the presence of PB antigen on most EBV-transformed B lymphocytes, and its appearance in each of the transformed lymphocytes of patients with acute infectious mononucleosis.", "contents": "Reactivity of Paul-Bunnell type heterophile antibody in sera from infectious mononucleosis patients with the surface of lymphoid cells carrying Epstein-Barr virus genomes. The possible presence of Paul-Bunnell (PB) antigen on Epstein-Barr virus (EBV)-transformed lymphocytes were investigated. Of 23 EBV genome-positive lymphoblastoid cell lines tested all but one absorbed PB type antibody from the serum of an infectious mononucleosis patient. The one EBV-negative B cell line tested did not absorb the heterophile antibody. PB antibody, purified by an immunoadsorbent procedure using beef cell antigen, reacted with the EBV producer P3HR-1 cell line in an indirect membrane immunofluorescence test and was shown to be IgM antibody. Titers of heterophile agglutinin and reactivity with the cell surface were reduced to the same degree by absorption with beef cell antigen but not with guinea pig kidney antigen. PB antibody was distinct from IgM antibody against the EBV-determined membrane antigen, since the latter was not absorbed by beef cell antigen. PB antibody was also reactive with other EBV-positive B cell lines (QIMR-WIL, NC-37, and Raji) which were free of surface IgM. No reaction occurred with the nonproducer P3HR-1 line, a null cell line, and two T cell lines. The results suggest the presence of PB antigen on most EBV-transformed B lymphocytes, and its appearance in each of the transformed lymphocytes of patients with acute infectious mononucleosis."}
{"id": "PMID:231731", "title": "Antigenic analysis of human cytomegalovirus isolates from Japanese women and infants.", "content": "The antigenic differences among human cytomegalovirus (CMV), two laboratory strains (Davis, AD 169), isolates from pregnant women's cervical secretions, mother's milk, infants' throat swabs and urine were analyzed by means of the plaque reduction assay using human sera which were assumed to contain monotypic antibodies by primary infection and boosted antibodies by reinfection or reactivation of the latent virus. In the cross-neutralization tests, there were no remarkable differences among the CMV strains examined. Moreover, in the neutralization kinetics, normalized kappa values among the strains constantly exceeded 80. Therefore, it is suggested that the human CMV strains examined in the study were serologically identical or very closely related.", "contents": "Antigenic analysis of human cytomegalovirus isolates from Japanese women and infants. The antigenic differences among human cytomegalovirus (CMV), two laboratory strains (Davis, AD 169), isolates from pregnant women's cervical secretions, mother's milk, infants' throat swabs and urine were analyzed by means of the plaque reduction assay using human sera which were assumed to contain monotypic antibodies by primary infection and boosted antibodies by reinfection or reactivation of the latent virus. In the cross-neutralization tests, there were no remarkable differences among the CMV strains examined. Moreover, in the neutralization kinetics, normalized kappa values among the strains constantly exceeded 80. Therefore, it is suggested that the human CMV strains examined in the study were serologically identical or very closely related."}
{"id": "PMID:231733", "title": "Carcinogenicity of fibers and films: a theory.", "content": "A theory based on frustrated phagocytosis is advanced to explain the carcinogenesis of fibers and films. Exocytosis combined with flexion of a foreign body permits the escape of superoxide radicals which, in a manner similar to that postulated for ionizing radiation, induces somatic mutations. The theory is subject to experimental verification, and offers hope for the development of preventive therapy which can be used to prevent some of the fibrosis and cancer resulting from asbestos inhalation.", "contents": "Carcinogenicity of fibers and films: a theory. A theory based on frustrated phagocytosis is advanced to explain the carcinogenesis of fibers and films. Exocytosis combined with flexion of a foreign body permits the escape of superoxide radicals which, in a manner similar to that postulated for ionizing radiation, induces somatic mutations. The theory is subject to experimental verification, and offers hope for the development of preventive therapy which can be used to prevent some of the fibrosis and cancer resulting from asbestos inhalation."}
{"id": "PMID:231734", "title": "Autonomic neural control of liver glycogen metabolism.", "content": "Neural and humoral induction of hepatic glycogenolysis occurs via different pathways. Sympathetic nerve stimulation activates alpha adrenergic receptors to produce what is probably a cyclic AMP independent, Ca++ dependent activation of glycogen phosphorylase. Evidence suggests that phosphorylase 'a' is activated by inhibition of phosphorylase phosphatase and perhaps by activation of phosphorylase kinase. Blood borne catecholamines act via beta adrenergic receptors to produce a cyclic AMP dependent activation of phosphorylase kinase. Additionally, hepatic parasympathetic nerves can produce a dramatic shut-down of hepatic glucose output by activation of glycogen synthetase and inhibition of glycogen phosphorylase. The observed minor effect of insulin or intravenous glucose on hepatic glucose uptake compared to the effect of oral doses of glucose suggests that an additional factor other than insulin can produce hepatic glucose uptake: this factor could be, and probably is, the hepatic parasympathetic nerves. The present hypotheses result from a combination and extrapolation of whole animal physiological and in vitro biochemical data.", "contents": "Autonomic neural control of liver glycogen metabolism. Neural and humoral induction of hepatic glycogenolysis occurs via different pathways. Sympathetic nerve stimulation activates alpha adrenergic receptors to produce what is probably a cyclic AMP independent, Ca++ dependent activation of glycogen phosphorylase. Evidence suggests that phosphorylase 'a' is activated by inhibition of phosphorylase phosphatase and perhaps by activation of phosphorylase kinase. Blood borne catecholamines act via beta adrenergic receptors to produce a cyclic AMP dependent activation of phosphorylase kinase. Additionally, hepatic parasympathetic nerves can produce a dramatic shut-down of hepatic glucose output by activation of glycogen synthetase and inhibition of glycogen phosphorylase. The observed minor effect of insulin or intravenous glucose on hepatic glucose uptake compared to the effect of oral doses of glucose suggests that an additional factor other than insulin can produce hepatic glucose uptake: this factor could be, and probably is, the hepatic parasympathetic nerves. The present hypotheses result from a combination and extrapolation of whole animal physiological and in vitro biochemical data."}
{"id": "PMID:231735", "title": "The mechanism of hyperlipidaemia in the nephrotic syndrome.", "content": "The mechanism of hyperlipidaemia in the nephrotic syndrome has not been fully established. We propose that it results from hypoalbuminaemia due to inhibition of the reaction catalysed by lecithin cholesterol acyltransferase converting cholesterol of high density lipoproteins to cholesterol esters and to an inhibition of high density lipoprotein particle formation from very low density lipoproteins due to reduced activity of lipoprotein lipase.", "contents": "The mechanism of hyperlipidaemia in the nephrotic syndrome. The mechanism of hyperlipidaemia in the nephrotic syndrome has not been fully established. We propose that it results from hypoalbuminaemia due to inhibition of the reaction catalysed by lecithin cholesterol acyltransferase converting cholesterol of high density lipoproteins to cholesterol esters and to an inhibition of high density lipoprotein particle formation from very low density lipoproteins due to reduced activity of lipoprotein lipase."}
{"id": "PMID:231736", "title": "Amelioration of cancer chemotherapy-induced nausea and vomiting by delta-9-tetrahydrocannabinol.", "content": "The antinausea and antivomiting effects of delta-9-tetrahydrocannabinol (THC) in children receiving cancer chemotherapy were compared with those of metoclopramide syrup and prochlorperazine tablets in two double-blind studies. THC was found to be a significantly better antinausea and antivomiting agent, but not all patients obtained relief of nausea and vomiting with THC. In some patients, THC enhanced appetite during a course of chemotherapy. In two patients, a \"high\" associated with THC administrationwas reported. Drowsiness was reported significantly more frequently with THC.", "contents": "Amelioration of cancer chemotherapy-induced nausea and vomiting by delta-9-tetrahydrocannabinol. The antinausea and antivomiting effects of delta-9-tetrahydrocannabinol (THC) in children receiving cancer chemotherapy were compared with those of metoclopramide syrup and prochlorperazine tablets in two double-blind studies. THC was found to be a significantly better antinausea and antivomiting agent, but not all patients obtained relief of nausea and vomiting with THC. In some patients, THC enhanced appetite during a course of chemotherapy. In two patients, a \"high\" associated with THC administrationwas reported. Drowsiness was reported significantly more frequently with THC."}
{"id": "PMID:231737", "title": "[Ketotifen, a new prophylactic agent in asthma (author's transl)].", "content": "12 patients with bronchial asthma received treatment with Ketotifen for three months. 8 patients then continued this medication for at least 9 months. During this period it was possible to reduce the amount of theophylline and bronchodilator amines as well as the maintenance dose of corticosteroids. Afterwards 6 patients showed clinical deterioration while on placebo; this was considered further evidence of the anti-asthmatic effect of Ketotifen. Ketotifen seems to be acceptable as a prophylactic agent in asthma.", "contents": "[Ketotifen, a new prophylactic agent in asthma (author's transl)]. 12 patients with bronchial asthma received treatment with Ketotifen for three months. 8 patients then continued this medication for at least 9 months. During this period it was possible to reduce the amount of theophylline and bronchodilator amines as well as the maintenance dose of corticosteroids. Afterwards 6 patients showed clinical deterioration while on placebo; this was considered further evidence of the anti-asthmatic effect of Ketotifen. Ketotifen seems to be acceptable as a prophylactic agent in asthma."}
{"id": "PMID:231738", "title": "[Effect of x-ray contrast media on the blood coagulation and fibrinolysis systems].", "content": "The intravenous application of x-ray contrast media during arteriographies resulted in a small, statistically significant, however clinically and biologically not relevant prolongation of the thromboplastin time and of the thrombincoagulase time. Contrast media applied for the examination of the kidneys and of the gall bladder did not induce any comparable changes of coagulation parameters. In vitro addition of iodinated contrast media to citrated plasmas was inhibitory to the coagulation process. Further analysis demonstrated that contrast media did not influence coagulation by enzyme inhibition but by inhibition of fibrin polymerization. Euglobulin lysis time was not only shortened by diagnostic applications of contrast media but also by other diagnostic procedures (gastroscopies, rectoscopies, laparoscopies) which involved physical exercise and thereby activation of the fibrinolytic system. Finally it is discussed that thrombotic complications following angiographies might be induced by the punction and injury of the vessel with the liberation of thrombokinase and subendothelial collagen.", "contents": "[Effect of x-ray contrast media on the blood coagulation and fibrinolysis systems]. The intravenous application of x-ray contrast media during arteriographies resulted in a small, statistically significant, however clinically and biologically not relevant prolongation of the thromboplastin time and of the thrombincoagulase time. Contrast media applied for the examination of the kidneys and of the gall bladder did not induce any comparable changes of coagulation parameters. In vitro addition of iodinated contrast media to citrated plasmas was inhibitory to the coagulation process. Further analysis demonstrated that contrast media did not influence coagulation by enzyme inhibition but by inhibition of fibrin polymerization. Euglobulin lysis time was not only shortened by diagnostic applications of contrast media but also by other diagnostic procedures (gastroscopies, rectoscopies, laparoscopies) which involved physical exercise and thereby activation of the fibrinolytic system. Finally it is discussed that thrombotic complications following angiographies might be induced by the punction and injury of the vessel with the liberation of thrombokinase and subendothelial collagen."}
{"id": "PMID:231741", "title": "Bronchial cancer in Hong Kong, 1976-77: a preliminary report.", "content": "A case-control study of the relationship of bronchial cancer to smoking was conducted during 1976-77 in Hong Kong, in which we took particular note of the histologic type of the tumor. A total of 132 male and 111 female patients were interviewed. The association with smoking was more evident in males than it was in females, and squamous and small-cell type carcinomas, as a group, appeared to be more closely associated with smoking than did adenocarcinomas and large cell tumors. Of the women with bronchial carcinoma, 44% were nonsmokers; 79% of their tumors were adenocarcinomas or large cell carcinomas. For the women in this group, no association could be detected with place of residence, occupation, or use of kerosene for cooking.", "contents": "Bronchial cancer in Hong Kong, 1976-77: a preliminary report. A case-control study of the relationship of bronchial cancer to smoking was conducted during 1976-77 in Hong Kong, in which we took particular note of the histologic type of the tumor. A total of 132 male and 111 female patients were interviewed. The association with smoking was more evident in males than it was in females, and squamous and small-cell type carcinomas, as a group, appeared to be more closely associated with smoking than did adenocarcinomas and large cell tumors. Of the women with bronchial carcinoma, 44% were nonsmokers; 79% of their tumors were adenocarcinomas or large cell carcinomas. For the women in this group, no association could be detected with place of residence, occupation, or use of kerosene for cooking."}
{"id": "PMID:231742", "title": "Elementary components of synaptic transmission.", "content": "The analysis of chemical transmission at synapses, in particular at the neuromuscular junction, has proceeded from the cellular to the molecular level. Gradual refinements in electric recording technique have brought to light new features, first the quantal delivery of the transmitter substance, in multimolecular packets, from the nerve endings, and more recently the statistical elements of the postsynaptic potential change which arise from the molecular bombardment by acetylcholine and the transient opening of individual ion channels in the end-plate membrane.", "contents": "Elementary components of synaptic transmission. The analysis of chemical transmission at synapses, in particular at the neuromuscular junction, has proceeded from the cellular to the molecular level. Gradual refinements in electric recording technique have brought to light new features, first the quantal delivery of the transmitter substance, in multimolecular packets, from the nerve endings, and more recently the statistical elements of the postsynaptic potential change which arise from the molecular bombardment by acetylcholine and the transient opening of individual ion channels in the end-plate membrane."}
{"id": "PMID:231746", "title": "Mucolipidosis IV.", "content": "Five new cases of Mucolipidosis IV are related and the seven cases in the literature reviewed. Neurological signs of the disorder and the value of skin and conjuncitival biopsies for its diagnosis are emphasized. Arguments in favour of a recessive autosomic inheritance are brought forth. The disease does not affect exclusively Jewish people. In two cases absence of oligosacchariduria was demonstrated.", "contents": "Mucolipidosis IV. Five new cases of Mucolipidosis IV are related and the seven cases in the literature reviewed. Neurological signs of the disorder and the value of skin and conjuncitival biopsies for its diagnosis are emphasized. Arguments in favour of a recessive autosomic inheritance are brought forth. The disease does not affect exclusively Jewish people. In two cases absence of oligosacchariduria was demonstrated."}
{"id": "PMID:231747", "title": "Cranial computed tomography (CCT) findings in children treated with ACTH and dexamethasone: first results.", "content": "8 children with different petit mal epilepsies were systematically treated with ACTH and dexamethasone. CCT examinations were performed before, during and after treatment. In all children severe cerebral changes. enlargement of ventricles and subarachnoid space developed during the initial phase of treatment with Depot-ACTH. Similar changes, but to a less severe degree, could be demonstrated during the phase of dexamethasone therapy thereafter. In all patients cerebral changes disappeared after hormonal treatment had ended. At this point many children had a developmental spurt, developmental relapses could not be observed. It is suggested that these reversible changes seen on CCT scans represent a form of morphological plasticity of brain structures. These results bear certain consequences as to the therapy of cerebral edema.", "contents": "Cranial computed tomography (CCT) findings in children treated with ACTH and dexamethasone: first results. 8 children with different petit mal epilepsies were systematically treated with ACTH and dexamethasone. CCT examinations were performed before, during and after treatment. In all children severe cerebral changes. enlargement of ventricles and subarachnoid space developed during the initial phase of treatment with Depot-ACTH. Similar changes, but to a less severe degree, could be demonstrated during the phase of dexamethasone therapy thereafter. In all patients cerebral changes disappeared after hormonal treatment had ended. At this point many children had a developmental spurt, developmental relapses could not be observed. It is suggested that these reversible changes seen on CCT scans represent a form of morphological plasticity of brain structures. These results bear certain consequences as to the therapy of cerebral edema."}
{"id": "PMID:231748", "title": "Krabbe's disease with unusual clinical and morphological features.", "content": "A progressive encephalopathy appeared in two sibs aged 7 and 5 months. The children died at 23 respectively 29 months of age. Autopsy of the second child disclosed a severe demyelination involving the whole brain. Only few globoid cells were identified. Ultrastructural and biochemical investigations confirmed the diagnosis of Krabbe's disease.", "contents": "Krabbe's disease with unusual clinical and morphological features. A progressive encephalopathy appeared in two sibs aged 7 and 5 months. The children died at 23 respectively 29 months of age. Autopsy of the second child disclosed a severe demyelination involving the whole brain. Only few globoid cells were identified. Ultrastructural and biochemical investigations confirmed the diagnosis of Krabbe's disease."}
{"id": "PMID:231745", "title": "Chronological study of ultrastructural changes in the peripheral nerves in Marek's disease.", "content": "A chronological study was made of the ultrastructural changes in peripheral nerves following inoculation of 1-day-old chicks with a neurogenic strain of Marek Disease virus. No virus particles were found in nerves. Cellular infiltration of nerves was detected as early as 5 days after inoculation and by 3 weeks some nerves contained proliferative lesions which possessed many of the ultrastructural features characteristic of normal, reactive lymphoid tissue. About 4 weeks after inoculation, coinciding with the onset of neurological signs, areas of widespread demyelination appeared within these lesions; lymphocytes and macrophages penetrated and destroyed the myelin sheath, but spared Schwann cells and most axons. Later oedematous, sparsely infiltrated B type lesions were observed, some of which contained demyelinated nerve fibres undergoing repair; these were therefore a stage in the regression of the proliferative lesions. Our observations do not favour the hypothesis that cellular infiltration of nerves in Marek's disease is the direct result of auto-sensitization to normal myelin. They are consistent with the hypothesis that demyelination is a secondary feature and that the primary lesions are preferential sites for immune demyelination.", "contents": "Chronological study of ultrastructural changes in the peripheral nerves in Marek's disease. A chronological study was made of the ultrastructural changes in peripheral nerves following inoculation of 1-day-old chicks with a neurogenic strain of Marek Disease virus. No virus particles were found in nerves. Cellular infiltration of nerves was detected as early as 5 days after inoculation and by 3 weeks some nerves contained proliferative lesions which possessed many of the ultrastructural features characteristic of normal, reactive lymphoid tissue. About 4 weeks after inoculation, coinciding with the onset of neurological signs, areas of widespread demyelination appeared within these lesions; lymphocytes and macrophages penetrated and destroyed the myelin sheath, but spared Schwann cells and most axons. Later oedematous, sparsely infiltrated B type lesions were observed, some of which contained demyelinated nerve fibres undergoing repair; these were therefore a stage in the regression of the proliferative lesions. Our observations do not favour the hypothesis that cellular infiltration of nerves in Marek's disease is the direct result of auto-sensitization to normal myelin. They are consistent with the hypothesis that demyelination is a secondary feature and that the primary lesions are preferential sites for immune demyelination."}
{"id": "PMID:231752", "title": "[Early bronchiolar-alveolar cell cicatricial carcinoma; a case report with 2 illustrations].", "content": "Only the solitary type of bronchiolo-alveolar cell carcinoma has a chance of being healed if surgery is performed in time. This type of tumor is often found as a cicatricial carcinoma in the periphery of the lung. Small tumors do not exhibit any clinical symptoms, they are either detected by mere chance or during radiological check-up or routine medical check-up of healthy persons. In the present case a small posttuberculous scar in the lung had been known to exist for ten years. Only a repeated routine medical check-up including X-ray examination and subsequent tomographic X-ray gave an indication for the performance of thoracotomy. While surgery was being performed the malignancy and the tumor type where cytologically determined and verified by histological examination of the excised tumor.", "contents": "[Early bronchiolar-alveolar cell cicatricial carcinoma; a case report with 2 illustrations]. Only the solitary type of bronchiolo-alveolar cell carcinoma has a chance of being healed if surgery is performed in time. This type of tumor is often found as a cicatricial carcinoma in the periphery of the lung. Small tumors do not exhibit any clinical symptoms, they are either detected by mere chance or during radiological check-up or routine medical check-up of healthy persons. In the present case a small posttuberculous scar in the lung had been known to exist for ten years. Only a repeated routine medical check-up including X-ray examination and subsequent tomographic X-ray gave an indication for the performance of thoracotomy. While surgery was being performed the malignancy and the tumor type where cytologically determined and verified by histological examination of the excised tumor."}
{"id": "PMID:231753", "title": "[Enophthalmic orbital metastasis].", "content": "Some orbital metastases (16 cases in the literature and 2 personal cases) involve a histologically typical enophtalmos with profuse fibrous stroma. They arise after squirrhous carcinoma of the breast or plastic linitis of the stomach.", "contents": "[Enophthalmic orbital metastasis]. Some orbital metastases (16 cases in the literature and 2 personal cases) involve a histologically typical enophtalmos with profuse fibrous stroma. They arise after squirrhous carcinoma of the breast or plastic linitis of the stomach."}
{"id": "PMID:231754", "title": "Microassay of cyclic nucleotides in vessel wall. IV. Cyclic GMP phosphodiesterase activity.", "content": "Following our microassay for cyclic AMP phosphodiesterase (1978, Microvascular Res. 15:229), a new microassay for cyclic GMP phosphodiesterase (c-GMPPDE) activity was devised, combining the quantitative histochemical method of O.H. Lowry and J.V. Passonneau (1971, A Flexible System of Enzymatic Analysis, Academic Press, New York) with the thin-layer chromatography method of W.A. Scott and B. Solomon (1973, Biochem. Biophys. Res. Comm., 53, 1024). Using this method, c-GMPPDE activity can be accurately measured in a 250 microgram dry weight sample of tissue from the aortic wall. The optimal amount of sample and incubation time were studied, and two Km values were obtained. Low Km is 4.00 x 10(-6) and high Km is 1.25 x 10(-5). The activity of this enzyme was measured in the intima and media of the aorta of three rabbits, three cows and three pigs. The cyclic GMPPDE activities in tissue from cows, pigs and rabbits were 26.61 +/- 2.19, 20.40 +/- 1.35, 43.08 +/- 4.11 pmole/mg dry weight/min in the intima; 52.56 +/- 2.73, 16.07 +/- 3.30 and 66.51 +/- 4.60 pmole/mg dry weight/min in the media. With regard to the relationship between levels of cAMP and cGMP, the activities of cGMPPDE were 10-20 times higher than those of cAMPPDE. These assay systems should provide accurate tools for researching biological, physiological and pathological states of arterial tissues, particularly in the case of atherosclerosis.", "contents": "Microassay of cyclic nucleotides in vessel wall. IV. Cyclic GMP phosphodiesterase activity. Following our microassay for cyclic AMP phosphodiesterase (1978, Microvascular Res. 15:229), a new microassay for cyclic GMP phosphodiesterase (c-GMPPDE) activity was devised, combining the quantitative histochemical method of O.H. Lowry and J.V. Passonneau (1971, A Flexible System of Enzymatic Analysis, Academic Press, New York) with the thin-layer chromatography method of W.A. Scott and B. Solomon (1973, Biochem. Biophys. Res. Comm., 53, 1024). Using this method, c-GMPPDE activity can be accurately measured in a 250 microgram dry weight sample of tissue from the aortic wall. The optimal amount of sample and incubation time were studied, and two Km values were obtained. Low Km is 4.00 x 10(-6) and high Km is 1.25 x 10(-5). The activity of this enzyme was measured in the intima and media of the aorta of three rabbits, three cows and three pigs. The cyclic GMPPDE activities in tissue from cows, pigs and rabbits were 26.61 +/- 2.19, 20.40 +/- 1.35, 43.08 +/- 4.11 pmole/mg dry weight/min in the intima; 52.56 +/- 2.73, 16.07 +/- 3.30 and 66.51 +/- 4.60 pmole/mg dry weight/min in the media. With regard to the relationship between levels of cAMP and cGMP, the activities of cGMPPDE were 10-20 times higher than those of cAMPPDE. These assay systems should provide accurate tools for researching biological, physiological and pathological states of arterial tissues, particularly in the case of atherosclerosis."}
{"id": "PMID:231757", "title": "Cystic partially differentiated nephroblastoma: an entity in the spectrum of infantile renal neoplasia.", "content": "Clinicopathologic features of 17 cases of \"cystic partially differentiated nephroblastoma\" (CPDN) including three seen in personal experience have been reviewed. CPDN has previously been designated by various terms such as \"benign multilocular cystic nephroma,\" \"polycystic nephroblastoma,\" and \"cystic nephroma.\" The term CPDN is preferred because it aptly denotes the characteristic gross and microscopic features and the probable histogenesis of the lesion. CPDN occurs before 2 years of age. Clinically, abdominal mass is the most common presenting feature. CPDN is often diagnosed as Wilms' tumor on clinical and radiologic grounds. Grossly, the lesion is almost totally or predominantly multicystic. Microscopically, the cysts are usually lined by flattened to cuboidal epithelium. The septa contain a mixture of blastemal cells and poorly differentiated and well-differentiated epithelial and mesenchymal elements. It is this feature which distinguishes CPDN from multilocular cyst of the kidney. Although there is a suggestion that there might be two subtypes of CPDN-one with predominantly well-differentiated elements and the other with predominantly poorly differentiated elements-no definite conclusions can be drawn regarding the existence of such subtypes on the basis of available data. Arguments could be advanced in favor of both the neoplastic and dysgenetic nature of CPDN. However, the view that CPDN is a neoplastic lesion is favored. On the basis of available data, CPDN appears to take a benign course, and simple nephrectomy seems to be the treatment of choice. However, in view of the possibility of recurrence as shown by rare cases of congenital mesoblastic nephroma (another usually benign lesion in the spectrum of infantile renal necoplasia), regular follow-up is recommended.", "contents": "Cystic partially differentiated nephroblastoma: an entity in the spectrum of infantile renal neoplasia. Clinicopathologic features of 17 cases of \"cystic partially differentiated nephroblastoma\" (CPDN) including three seen in personal experience have been reviewed. CPDN has previously been designated by various terms such as \"benign multilocular cystic nephroma,\" \"polycystic nephroblastoma,\" and \"cystic nephroma.\" The term CPDN is preferred because it aptly denotes the characteristic gross and microscopic features and the probable histogenesis of the lesion. CPDN occurs before 2 years of age. Clinically, abdominal mass is the most common presenting feature. CPDN is often diagnosed as Wilms' tumor on clinical and radiologic grounds. Grossly, the lesion is almost totally or predominantly multicystic. Microscopically, the cysts are usually lined by flattened to cuboidal epithelium. The septa contain a mixture of blastemal cells and poorly differentiated and well-differentiated epithelial and mesenchymal elements. It is this feature which distinguishes CPDN from multilocular cyst of the kidney. Although there is a suggestion that there might be two subtypes of CPDN-one with predominantly well-differentiated elements and the other with predominantly poorly differentiated elements-no definite conclusions can be drawn regarding the existence of such subtypes on the basis of available data. Arguments could be advanced in favor of both the neoplastic and dysgenetic nature of CPDN. However, the view that CPDN is a neoplastic lesion is favored. On the basis of available data, CPDN appears to take a benign course, and simple nephrectomy seems to be the treatment of choice. However, in view of the possibility of recurrence as shown by rare cases of congenital mesoblastic nephroma (another usually benign lesion in the spectrum of infantile renal necoplasia), regular follow-up is recommended."}
{"id": "PMID:231759", "title": "Separate activation sites for cholecystokinin and bombesin on pancreatic acini: an electrophysiological study employing a competitive antagonist for the action of CCK.", "content": "The effects of dibutyryl cyclic guanosine 3':5' monophosphate (dbcGMP) on the electrical responses of in vitro mouse pancreatic acinar cells to caerulein, bombesin and acetylcholine, applied by microionophoresis, were investigated using intracellular microelectrode recordings. Exposure to dbcGMP (10(-3) mol . 1-1) quickly abolished the depolarization response to caerulein ionophoresis, while the bombesin-nonapeptide and acetylcholine-induced depolarizations were retained. Exposing acinar cells to 2 x 10(-4) mol . 1-1 dbcGMP reduced their sensitivity such that a 10-fold increase in the applied caerulein ionophoresis current was required to restore the responses to the same magnitude as those obtained in a dbcGMP-free environment. The response to topical applications of pentagastrin and CCK-33 were also abolished by dbcGMP. The results provide direct evidence that functional ACh, bombesin and CCK receptors are all present within the same acinar cell unit. The dbcGMP-induced inhibition of responses evoked by CCK-like peptides is immediate, specific and easily reversible. DbcGMP acts as a competitive antagonist of the CCK receptor on pancreatic acinar cells.", "contents": "Separate activation sites for cholecystokinin and bombesin on pancreatic acini: an electrophysiological study employing a competitive antagonist for the action of CCK. The effects of dibutyryl cyclic guanosine 3':5' monophosphate (dbcGMP) on the electrical responses of in vitro mouse pancreatic acinar cells to caerulein, bombesin and acetylcholine, applied by microionophoresis, were investigated using intracellular microelectrode recordings. Exposure to dbcGMP (10(-3) mol . 1-1) quickly abolished the depolarization response to caerulein ionophoresis, while the bombesin-nonapeptide and acetylcholine-induced depolarizations were retained. Exposing acinar cells to 2 x 10(-4) mol . 1-1 dbcGMP reduced their sensitivity such that a 10-fold increase in the applied caerulein ionophoresis current was required to restore the responses to the same magnitude as those obtained in a dbcGMP-free environment. The response to topical applications of pentagastrin and CCK-33 were also abolished by dbcGMP. The results provide direct evidence that functional ACh, bombesin and CCK receptors are all present within the same acinar cell unit. The dbcGMP-induced inhibition of responses evoked by CCK-like peptides is immediate, specific and easily reversible. DbcGMP acts as a competitive antagonist of the CCK receptor on pancreatic acinar cells."}
{"id": "PMID:231760", "title": "[Persistent non polio enterovirus infections associated with glomerulonephritis. 9 cases (author's transl)].", "content": "All patients are excreting the virus in urines and in 4 cases in stools. The virus has also been isolated from the blood. These cases focused on the possible role of enteroviruses as causal agents for the glomerulonephritis.", "contents": "[Persistent non polio enterovirus infections associated with glomerulonephritis. 9 cases (author's transl)]. All patients are excreting the virus in urines and in 4 cases in stools. The virus has also been isolated from the blood. These cases focused on the possible role of enteroviruses as causal agents for the glomerulonephritis."}
{"id": "PMID:231762", "title": "The nucleotide sequence at the 5' end of foot and mouth disease virus RNA.", "content": "Foot and mouth disease virus RNA has been treated with RNase H in the presence of oligo (dG) specifically to digest the poly(C) tract which lies near the 5' end of the molecule (10). The short (S) fragment containing the 5' end of the RNA was separated from the remainder of the RNA (L fragment) by gel electrophoresis. RNA ligase mediated labelling of the 3' end of S fragment showed that the RNase H digestion gave rise to molecules that differed only in the number of cytidylic acid residues remaining at their 3' ends and did not leave the unique 3' end necessary for fast sequence analysis. As the 5' end of S fragment prepared form virus RNA is blocked by VPg, S fragment was prepared from virus specific messenger RNA which does not contain this protein. This RNA was labelled at the 5' end using polynucleotide kinase and the sequence of 70 nucleotides at the 5' end determined by partial enzyme digestion sequencing on polyacrylamide gels. Some of this sequence was confirmed from an analysis of the oligonucleotides derived by RNase T1 digestion of S fragment. The sequence obtained indicates that there is a stable hairpin loop at the 5' terminus of the RNA before an initiation codon 33 nucleotides from the 5' end. In addition, the RNase T1 analysis suggests that there are short repeated sequences in S fragment and that an eleven nucleotide inverted complementary repeat of a sequence near the 3' end of the RNA is present at the junction of S fragment and the poly(C) tract.", "contents": "The nucleotide sequence at the 5' end of foot and mouth disease virus RNA. Foot and mouth disease virus RNA has been treated with RNase H in the presence of oligo (dG) specifically to digest the poly(C) tract which lies near the 5' end of the molecule (10). The short (S) fragment containing the 5' end of the RNA was separated from the remainder of the RNA (L fragment) by gel electrophoresis. RNA ligase mediated labelling of the 3' end of S fragment showed that the RNase H digestion gave rise to molecules that differed only in the number of cytidylic acid residues remaining at their 3' ends and did not leave the unique 3' end necessary for fast sequence analysis. As the 5' end of S fragment prepared form virus RNA is blocked by VPg, S fragment was prepared from virus specific messenger RNA which does not contain this protein. This RNA was labelled at the 5' end using polynucleotide kinase and the sequence of 70 nucleotides at the 5' end determined by partial enzyme digestion sequencing on polyacrylamide gels. Some of this sequence was confirmed from an analysis of the oligonucleotides derived by RNase T1 digestion of S fragment. The sequence obtained indicates that there is a stable hairpin loop at the 5' terminus of the RNA before an initiation codon 33 nucleotides from the 5' end. In addition, the RNase T1 analysis suggests that there are short repeated sequences in S fragment and that an eleven nucleotide inverted complementary repeat of a sequence near the 3' end of the RNA is present at the junction of S fragment and the poly(C) tract."}
{"id": "PMID:231763", "title": "Characterization of the major altered leader sequence of late mRNA induced by SV40 deletion mutant d1-1811.", "content": "d1-1811 is a viable SV40 mutant with a 40 base pair deletion that includes the major wild-type capping site of late mRNA at map position 0.72. The late viral mRNAs induced by d1-1811 have now been further characterized by inversed S1-mapping analysis. The S1-resistant, 32P-labeled RNA fragments derived from the leader region were examined by fingerprinting and by analysis of RNase T2-generated 5'-terminal cap structures. The results show that most if not all of the mutant leader fragments analyzed have their 5' terminus to the left of the d1-1811 deletion site, i.e., closer to the origin of DNA replication. The major altered leader fragment is a continuous transcript from the DNA in the region 0.716 to 0.761 map unit and its 5' terminus has been precisely mapped at nucleotide L290. The observation that the cap structure of the major altered leader is only a minor cap species in wild-type late RNA suggests regulation in the use of different capping sites in SV40.", "contents": "Characterization of the major altered leader sequence of late mRNA induced by SV40 deletion mutant d1-1811. d1-1811 is a viable SV40 mutant with a 40 base pair deletion that includes the major wild-type capping site of late mRNA at map position 0.72. The late viral mRNAs induced by d1-1811 have now been further characterized by inversed S1-mapping analysis. The S1-resistant, 32P-labeled RNA fragments derived from the leader region were examined by fingerprinting and by analysis of RNase T2-generated 5'-terminal cap structures. The results show that most if not all of the mutant leader fragments analyzed have their 5' terminus to the left of the d1-1811 deletion site, i.e., closer to the origin of DNA replication. The major altered leader fragment is a continuous transcript from the DNA in the region 0.716 to 0.761 map unit and its 5' terminus has been precisely mapped at nucleotide L290. The observation that the cap structure of the major altered leader is only a minor cap species in wild-type late RNA suggests regulation in the use of different capping sites in SV40."}
{"id": "PMID:231764", "title": "Rapid  mapping of transposon insertion and deletion mutations in the large Ti-plasmids of Agrobacterium tumefaciens.", "content": "A procedure is presented, that has allowed the rapid assignment of transposon Tn1 and Tn7 insertion sites in the large (130 Md) nopaline Ti-plasmid pTiC58, to specific restriction enzyme fragments. Total bacterial DNA is isolated from Agrobacterium tumefaciens strain C58 mutants that carry a transposon in their Ti-plasmid, and digested with an appropriate restriction endonuclease. The fragments are separated on an agarose gel, denatured and transferred to nitrocellulose filters. These are hybridized against purified wild type pTiC58, or against segments of PTiC58, cloned in E. coli using pBR322 as a vector plasmid. DNA sequences homologous to the probe are detected by autoradiography, thus generating a restriction enzyme pattern of the plasmid from a digest of total bacterial DNA. Mutant fragments can be readily identified by their different position compared to a wild type reference. This protocol eliminates the need to separate the large plasmid from chromosomal DNA for every mutant. In principle, it can be applied to the restriction enzyme analysis of insertion or deletion mutants in any plasmid that has no extensive homology with the chromosome.", "contents": "Rapid  mapping of transposon insertion and deletion mutations in the large Ti-plasmids of Agrobacterium tumefaciens. A procedure is presented, that has allowed the rapid assignment of transposon Tn1 and Tn7 insertion sites in the large (130 Md) nopaline Ti-plasmid pTiC58, to specific restriction enzyme fragments. Total bacterial DNA is isolated from Agrobacterium tumefaciens strain C58 mutants that carry a transposon in their Ti-plasmid, and digested with an appropriate restriction endonuclease. The fragments are separated on an agarose gel, denatured and transferred to nitrocellulose filters. These are hybridized against purified wild type pTiC58, or against segments of PTiC58, cloned in E. coli using pBR322 as a vector plasmid. DNA sequences homologous to the probe are detected by autoradiography, thus generating a restriction enzyme pattern of the plasmid from a digest of total bacterial DNA. Mutant fragments can be readily identified by their different position compared to a wild type reference. This protocol eliminates the need to separate the large plasmid from chromosomal DNA for every mutant. In principle, it can be applied to the restriction enzyme analysis of insertion or deletion mutants in any plasmid that has no extensive homology with the chromosome."}
{"id": "PMID:231765", "title": "The relationship between pyrimidine dimers and replicating DNA in UV-irradiated human fibroblasts.", "content": "The relationship between pyrimidine dimers (measured as endonuclease-sensitive sites) and newly-synthesized DNA has been examined in several different ways, with the following results:- 1. After UV-irradiation of normal human fibroblasts the frequency of pyrimidine dimer sites in sections of DNA which have been synthesized immediately before the UV-irradiation is similar to that in the bulk DNA. 2. The frequency of pyrimidine dimer sites in the parental strands of replicating DNA in UV-irradiated normal human fibroblasts is similar to that in the bulk DNA. 3. In UV-irradiated XP variant cells the size of DNA synthesized in the presence of caffeine immediately after UV irradiation accurately corresponds with the average interdimer distance in the parental DNA. This suggests that in this experimental situation each pyrimidine dimer gives rise to a disocntinuity or a termination site in the daughter strand.", "contents": "The relationship between pyrimidine dimers and replicating DNA in UV-irradiated human fibroblasts. The relationship between pyrimidine dimers (measured as endonuclease-sensitive sites) and newly-synthesized DNA has been examined in several different ways, with the following results:- 1. After UV-irradiation of normal human fibroblasts the frequency of pyrimidine dimer sites in sections of DNA which have been synthesized immediately before the UV-irradiation is similar to that in the bulk DNA. 2. The frequency of pyrimidine dimer sites in the parental strands of replicating DNA in UV-irradiated normal human fibroblasts is similar to that in the bulk DNA. 3. In UV-irradiated XP variant cells the size of DNA synthesized in the presence of caffeine immediately after UV irradiation accurately corresponds with the average interdimer distance in the parental DNA. This suggests that in this experimental situation each pyrimidine dimer gives rise to a disocntinuity or a termination site in the daughter strand."}
{"id": "PMID:231766", "title": "New genes and promoters suggested by the DNA sequence near the end of the coliphage T7 early operon.", "content": "We have employed the dideoxynucleotide chain-terminating method to determine the nucleotide sequence of T7 DNA between the physical map positions 18.9% and 19.8%. The most striking features of this sequence are two perfect 21-basepair repeats, each of which appears to contain a promoter for late transcription. In each case the promoter sequence incorporates a putative translational terminator on its left (5'-side of the \"sense\" strand), and overlaps a potential ribosome-binding site on its right. The region probably lies immediately distal to the early operon, and may contain two short, hitherto unreported protein-coding sequences.", "contents": "New genes and promoters suggested by the DNA sequence near the end of the coliphage T7 early operon. We have employed the dideoxynucleotide chain-terminating method to determine the nucleotide sequence of T7 DNA between the physical map positions 18.9% and 19.8%. The most striking features of this sequence are two perfect 21-basepair repeats, each of which appears to contain a promoter for late transcription. In each case the promoter sequence incorporates a putative translational terminator on its left (5'-side of the \"sense\" strand), and overlaps a potential ribosome-binding site on its right. The region probably lies immediately distal to the early operon, and may contain two short, hitherto unreported protein-coding sequences."}
{"id": "PMID:231767", "title": "RNA polymerase I from higher plants. Evidence for allosteric regulation and interaction with a nuclear phosphatase activity controlled NTP pool.", "content": "RNA polymerase I was isolated from parsley cells grown in suspension culture and from soybean hypocotyls. Kinetic studies of the enzyme revealed that RNA polymerase I is an allosteric regulated enzyme. The enzyme activity was influenced by nucleoside triphosphates (NTP) and divalent cations. NTP exceeding a 1:1 ratio of these two components acted as allosteric inhibitors, contrary to free divalent cations, which had promotive effects on the RNA polymerase I. Furthermore, isolated nuclei from parsley exhibited a powerful nucleoside triphosphatase (NTPase) activity. Contrary to RNA polymerase I, this enzyme was stimulated by NTP exceeding the 1:1 ratio of NTP and divalent cations. Free divalent cations had an inhibitory effect. Assuming that a causal connection of these two processes does exist, a possible role of this NTPase would be the control of NTP pools in relation to divalent cations and thus regulating RNA synthesis.", "contents": "RNA polymerase I from higher plants. Evidence for allosteric regulation and interaction with a nuclear phosphatase activity controlled NTP pool. RNA polymerase I was isolated from parsley cells grown in suspension culture and from soybean hypocotyls. Kinetic studies of the enzyme revealed that RNA polymerase I is an allosteric regulated enzyme. The enzyme activity was influenced by nucleoside triphosphates (NTP) and divalent cations. NTP exceeding a 1:1 ratio of these two components acted as allosteric inhibitors, contrary to free divalent cations, which had promotive effects on the RNA polymerase I. Furthermore, isolated nuclei from parsley exhibited a powerful nucleoside triphosphatase (NTPase) activity. Contrary to RNA polymerase I, this enzyme was stimulated by NTP exceeding the 1:1 ratio of NTP and divalent cations. Free divalent cations had an inhibitory effect. Assuming that a causal connection of these two processes does exist, a possible role of this NTPase would be the control of NTP pools in relation to divalent cations and thus regulating RNA synthesis."}
{"id": "PMID:231768", "title": "The binding of an avian myeloblastosis virus basic 12,000 dalton protein to nucleic acids.", "content": "The binding of a basic 12,000 dalton protein (p12) from avian myeloblastosis virus to viral RNA and heterologous DNA has been investigated. The binding stoichiometries and constants were determined by an extrinsic fluorescence assay. In both cases each bound p12 molecule occupies four nucleotides and the apparent binding constant is approximately 1 x 10(6) M-1. Binding is non-cooperative and there is no apparent difference in the interaction of p12 with viral RNA or heterologous single-strand DNA. The relative binding constant at various ionic strengths was assayed by the nitrocellulose filter procedure. Analysis of the data revealed that each bound p12 molecule forms three ion pairs with the nucleic acid.", "contents": "The binding of an avian myeloblastosis virus basic 12,000 dalton protein to nucleic acids. The binding of a basic 12,000 dalton protein (p12) from avian myeloblastosis virus to viral RNA and heterologous DNA has been investigated. The binding stoichiometries and constants were determined by an extrinsic fluorescence assay. In both cases each bound p12 molecule occupies four nucleotides and the apparent binding constant is approximately 1 x 10(6) M-1. Binding is non-cooperative and there is no apparent difference in the interaction of p12 with viral RNA or heterologous single-strand DNA. The relative binding constant at various ionic strengths was assayed by the nitrocellulose filter procedure. Analysis of the data revealed that each bound p12 molecule forms three ion pairs with the nucleic acid."}
{"id": "PMID:231769", "title": "Scintigraphic detection of gynaecological tumours by 99mTc-HSA blood pool imaging.", "content": "Three cases of scintigraphic visualization of gynaecological tumours by 99mTc-HSA blood pool imaging are presented, i.e. one case of fibrothecoma (\"cold\" area visualization) and two cases of fibromyoma (\"hot\" area visualization). It is suggested that this technique may be useful in the preoperative evaluation of gynaecological tumours and their vascularity.", "contents": "Scintigraphic detection of gynaecological tumours by 99mTc-HSA blood pool imaging. Three cases of scintigraphic visualization of gynaecological tumours by 99mTc-HSA blood pool imaging are presented, i.e. one case of fibrothecoma (\"cold\" area visualization) and two cases of fibromyoma (\"hot\" area visualization). It is suggested that this technique may be useful in the preoperative evaluation of gynaecological tumours and their vascularity."}
{"id": "PMID:231775", "title": "A suggested classification of breast pain.", "content": "A system of classification based on the work of Preece et al. (1976) is described. The results of applying this classification over a 4 month period (representing 84 patients) are described.", "contents": "A suggested classification of breast pain. A system of classification based on the work of Preece et al. (1976) is described. The results of applying this classification over a 4 month period (representing 84 patients) are described."}
{"id": "PMID:231776", "title": "An insulinoma presenting with reactive hypoglycaemia.", "content": "A 57-year-old woman presented with symptoms which were cured by the removal of an insulinoma. The case was atypical in that symptomatic hypoglycaemia occurred only after meals or glucose administration but never during fasting, and thus if plasma insulin activity had not been measured an incorrect diagnosis of reactive hypoglycaemia might have been made on the basis of symptoms and oral glucose-tolerance test. Reactive hypoglycaemia resulted from an increased rate of glucose assimilation and possibly also from a decreased rate of gluconeogenesis due to the immense insulin secretion provoked by glucose or food. The findings suggest that a diagnosis of hypoglycaemia should not be made until the possibility of an insulinoma has been excluded by measurement of plasma insulin activity during a period of hypoglycaemia.", "contents": "An insulinoma presenting with reactive hypoglycaemia. A 57-year-old woman presented with symptoms which were cured by the removal of an insulinoma. The case was atypical in that symptomatic hypoglycaemia occurred only after meals or glucose administration but never during fasting, and thus if plasma insulin activity had not been measured an incorrect diagnosis of reactive hypoglycaemia might have been made on the basis of symptoms and oral glucose-tolerance test. Reactive hypoglycaemia resulted from an increased rate of glucose assimilation and possibly also from a decreased rate of gluconeogenesis due to the immense insulin secretion provoked by glucose or food. The findings suggest that a diagnosis of hypoglycaemia should not be made until the possibility of an insulinoma has been excluded by measurement of plasma insulin activity during a period of hypoglycaemia."}
{"id": "PMID:231780", "title": "The heterogeneity of nerve growth factor receptors.", "content": "Chick embryonic sensory ganglia cells have two specific nerve growth factor receptors, site I and site II receptors, whose binding affinities differ by two orders of magnitude. As judged by both steady state binding and kinetic data, the two receptors behave independently. The rate of dissociation of the labeled nerve growth factor from site I receptors is increased in the presence of unlabeled nerve growth factor even when its concentration is below that of the labeled growth factor used to equilibrate the cells, a phenomenon which cannot be explained by negative cooperativity. Site I receptors are present only on neurons while site II receptors are present on both neurons and nonneuronal cells. At the concentration of nerve growth factor which produces half maximal stimulation of neurite outgrowth 8% of site I and 0.1% of site II receptors are occupied. This occupancy of site II receptors falls to about 0.01% with bisdesarginine beta nerve growth factor, a derivative which is as biologically active as the unmodified factor but which binds with lower affinity to site II receptors. These data support the idea that interaction of nerve growth factor with site I receptors is responsible for the initiation of neurite outgrowth.", "contents": "The heterogeneity of nerve growth factor receptors. Chick embryonic sensory ganglia cells have two specific nerve growth factor receptors, site I and site II receptors, whose binding affinities differ by two orders of magnitude. As judged by both steady state binding and kinetic data, the two receptors behave independently. The rate of dissociation of the labeled nerve growth factor from site I receptors is increased in the presence of unlabeled nerve growth factor even when its concentration is below that of the labeled growth factor used to equilibrate the cells, a phenomenon which cannot be explained by negative cooperativity. Site I receptors are present only on neurons while site II receptors are present on both neurons and nonneuronal cells. At the concentration of nerve growth factor which produces half maximal stimulation of neurite outgrowth 8% of site I and 0.1% of site II receptors are occupied. This occupancy of site II receptors falls to about 0.01% with bisdesarginine beta nerve growth factor, a derivative which is as biologically active as the unmodified factor but which binds with lower affinity to site II receptors. These data support the idea that interaction of nerve growth factor with site I receptors is responsible for the initiation of neurite outgrowth."}
{"id": "PMID:231779", "title": "[Immobilization of nicotine amide adenine dinucleotide derivatives and their function as cofactors of bacterial formic dehydrogenase].", "content": "NAD+ was modified with respect to the C(6)-amino group of the adenine residue by iod acetic acid alkylation in N1-position and subsequent rearrangement into N6-position. By condensation of N6-carboxy methyl-NAD+ with 1,6-diamino hexane, N6-[(6-aminohexyl)-acetamide]-NAD+ was synthesized. This process was controlled spectrophotometrically and by analytical isotachophoresis. NAD+ derivatives were found to maintain high co-enzymic activity in the reaction of formic oxidation with formic dehydrogenase from gram-negative methylotrophic bacteria, str. 1. Kinetic parameters of the reaction involving the resultant components were determined. NAD+N6-derivatives were covalently bound with the water insoluble carrier--Sepharose 4B and water soluble carriers--acrolein and 4-vinyl pyridine copolymers and dextran. The rates of formic dehydrogenase reduction of the native and immobilized cofactors were compared.", "contents": "[Immobilization of nicotine amide adenine dinucleotide derivatives and their function as cofactors of bacterial formic dehydrogenase]. NAD+ was modified with respect to the C(6)-amino group of the adenine residue by iod acetic acid alkylation in N1-position and subsequent rearrangement into N6-position. By condensation of N6-carboxy methyl-NAD+ with 1,6-diamino hexane, N6-[(6-aminohexyl)-acetamide]-NAD+ was synthesized. This process was controlled spectrophotometrically and by analytical isotachophoresis. NAD+ derivatives were found to maintain high co-enzymic activity in the reaction of formic oxidation with formic dehydrogenase from gram-negative methylotrophic bacteria, str. 1. Kinetic parameters of the reaction involving the resultant components were determined. NAD+N6-derivatives were covalently bound with the water insoluble carrier--Sepharose 4B and water soluble carriers--acrolein and 4-vinyl pyridine copolymers and dextran. The rates of formic dehydrogenase reduction of the native and immobilized cofactors were compared."}
{"id": "PMID:231783", "title": "Interaction of thyroid hormones with target tissues: effects of hepatic mRNA population.", "content": "Although the molecular basis of thyroid hormone action remains obscure, a growing body of evidence has suggested that triiodothyronine (T3) action is initiated at a set of specific nuclear receptor sites. The physiologic significance of these T3-binding sites is supported by four lines of evidence: 1) the high-affinity, limited-capacity binding of T3; 2) the relationship between binding affinity of thyroid hormone analogs and hormonal potency; 3) the correlation of concentration of nuclear receptor and physiologic response in various tissues; 4) the relationship between receptor occupancy and physiologic response. While the levels of hepatic nuclear receptor do not change in response to T3, recent evidence indicates receptor concentration is markedly reduced by partial hepatectomy, starvation, or administration of glucagon. This reduction results in a decrease in the response of malic enzyme to T3, but leaves the response of alpha-glycerol phosphate dehydrogenase unimpaired. Thus, specific control of thyroid responses by modulating receptor concentration may occur. Occupancy of hepatic receptors by T3 is associated with increases in both the rate of formation and steady-state concentration of poly(A)-containing mRNA. The values of these two parameters in the euthyroid rat liver were approximately 60--80% greater than values in hypothyroid animals. Analyses of the sequence and frequency complexity of poly(A)-containing mRNA from euthyroid and hypothyroid rats revealed no major changes in either the qualitative or quantitative distribution of mRNA sequences. Although it is recognized that the levels of certain specific species of mRNA (ie, alpha 2u-globulin) are altered as a result of thyroid hormone action, these data strongly indicate a concomitant generalized increase in the production of all major classes of mRNA.", "contents": "Interaction of thyroid hormones with target tissues: effects of hepatic mRNA population. Although the molecular basis of thyroid hormone action remains obscure, a growing body of evidence has suggested that triiodothyronine (T3) action is initiated at a set of specific nuclear receptor sites. The physiologic significance of these T3-binding sites is supported by four lines of evidence: 1) the high-affinity, limited-capacity binding of T3; 2) the relationship between binding affinity of thyroid hormone analogs and hormonal potency; 3) the correlation of concentration of nuclear receptor and physiologic response in various tissues; 4) the relationship between receptor occupancy and physiologic response. While the levels of hepatic nuclear receptor do not change in response to T3, recent evidence indicates receptor concentration is markedly reduced by partial hepatectomy, starvation, or administration of glucagon. This reduction results in a decrease in the response of malic enzyme to T3, but leaves the response of alpha-glycerol phosphate dehydrogenase unimpaired. Thus, specific control of thyroid responses by modulating receptor concentration may occur. Occupancy of hepatic receptors by T3 is associated with increases in both the rate of formation and steady-state concentration of poly(A)-containing mRNA. The values of these two parameters in the euthyroid rat liver were approximately 60--80% greater than values in hypothyroid animals. Analyses of the sequence and frequency complexity of poly(A)-containing mRNA from euthyroid and hypothyroid rats revealed no major changes in either the qualitative or quantitative distribution of mRNA sequences. Although it is recognized that the levels of certain specific species of mRNA (ie, alpha 2u-globulin) are altered as a result of thyroid hormone action, these data strongly indicate a concomitant generalized increase in the production of all major classes of mRNA."}
{"id": "PMID:231784", "title": "Regulation of pyruvate dehydrogenase by insulin action.", "content": "In animal tissues the pyruvate dehydrogenase complex is regulated by product inhibition and by a phosphorylation-dephosphorylation cycle catalysed by a kinase and a phosphatase. Physiologic and molecular aspects of this regulation are reviewed, and the results of recent studies are described. Insulin deficiency in the rat (diabetes or starvation) is shown to inhibit the conversion of inactive (phospho-) complex into active (dephospho-) complex by the phosphatase by an effect on the substrate for the phosphatase (phosphorylated complex). This change is stable and persists during isolation, incubation, and extraction of mitochondria or purification of phosphorylated complex. The subunit ratios in the purified pig heart pyruvate dehydrogenase complex and the stoichiometry of phosphorylations have been determined by radioamidination and incorporation of 32P. The ratios of decarboxylase tetramer (alpha 2, beta 2) : dihydrolipoyl acetyltransferase monomer : dihydrolipoly dehydrogenase monomer were 1:1:0.5. Inactivation of the complex was accomplished by incorporation of a single phosphate into one alpha subunit of the decarboxylase tetramer. Two further phosphates are then incorporated and these additional phosphorylations inhibit reactivation of the complex by the phosphate. It is suggested that multisite phosphorylations may inhibit reactivation of the complex by the phosphatase in diabetes and in starvation.", "contents": "Regulation of pyruvate dehydrogenase by insulin action. In animal tissues the pyruvate dehydrogenase complex is regulated by product inhibition and by a phosphorylation-dephosphorylation cycle catalysed by a kinase and a phosphatase. Physiologic and molecular aspects of this regulation are reviewed, and the results of recent studies are described. Insulin deficiency in the rat (diabetes or starvation) is shown to inhibit the conversion of inactive (phospho-) complex into active (dephospho-) complex by the phosphatase by an effect on the substrate for the phosphatase (phosphorylated complex). This change is stable and persists during isolation, incubation, and extraction of mitochondria or purification of phosphorylated complex. The subunit ratios in the purified pig heart pyruvate dehydrogenase complex and the stoichiometry of phosphorylations have been determined by radioamidination and incorporation of 32P. The ratios of decarboxylase tetramer (alpha 2, beta 2) : dihydrolipoyl acetyltransferase monomer : dihydrolipoly dehydrogenase monomer were 1:1:0.5. Inactivation of the complex was accomplished by incorporation of a single phosphate into one alpha subunit of the decarboxylase tetramer. Two further phosphates are then incorporated and these additional phosphorylations inhibit reactivation of the complex by the phosphate. It is suggested that multisite phosphorylations may inhibit reactivation of the complex by the phosphatase in diabetes and in starvation."}
{"id": "PMID:231786", "title": "Identification and partial characterization of some components of hormone-stimulated adenylate cyclase.", "content": "Adenylate cyclase can be resolved into at least two protein components, neither of which by itself catalyzes the formation of cyclic AMP with Mg-ATP as substrate. Mixture of the two reconstitutes Mg-ATP-dependent, fluoride- and Gpp(NH)p-stimulable activity. One, a heat-labile, N-ethylmaleimide-sensitive protein of molecular weight 190,000 can catalyze cyclic AMP formation with Mn-ATP as substrate, and is therefore proposed to be the catalytic moiety of the adenylate cyclase complex. The other protein (or proteins) is more resistant to heating or N-ethylmaleimide, and is proposed to confer upon the catalyst the ability to ultilize Mg-ATP as substrate. It is also required for the regulation of that activity by guanine nucleotides, hormones, and probably fluoride ion. The catalytic protein is found in a phenotypically adenylate cyclase-deficient (AC-) variant of S49 lymphoma cells. The thermostable regulatory protein can be resolved from the catalyst by heat treatment or N-ethylmaleimide treatment of plasma membranes of wild-type S49 cells, rat or rabbit liver, or avian erythrocytes, and is also found in a phenotypically adenylate cyclase-deficient hepatoma cell line. Mixture of AC- S49 membranes, which contain the beta-adrenergic receptor, with a crude detergent-solubilized preparation of the regulatory protein reconstitutes hormone-stimulable adenylate cyclase activity. Binding of the regulatory protein to the membranes is a time- and temperature-dependent process that requires an activating ligand of the adenylate cyclase system [fluoride, Gpp(NH)p].", "contents": "Identification and partial characterization of some components of hormone-stimulated adenylate cyclase. Adenylate cyclase can be resolved into at least two protein components, neither of which by itself catalyzes the formation of cyclic AMP with Mg-ATP as substrate. Mixture of the two reconstitutes Mg-ATP-dependent, fluoride- and Gpp(NH)p-stimulable activity. One, a heat-labile, N-ethylmaleimide-sensitive protein of molecular weight 190,000 can catalyze cyclic AMP formation with Mn-ATP as substrate, and is therefore proposed to be the catalytic moiety of the adenylate cyclase complex. The other protein (or proteins) is more resistant to heating or N-ethylmaleimide, and is proposed to confer upon the catalyst the ability to ultilize Mg-ATP as substrate. It is also required for the regulation of that activity by guanine nucleotides, hormones, and probably fluoride ion. The catalytic protein is found in a phenotypically adenylate cyclase-deficient (AC-) variant of S49 lymphoma cells. The thermostable regulatory protein can be resolved from the catalyst by heat treatment or N-ethylmaleimide treatment of plasma membranes of wild-type S49 cells, rat or rabbit liver, or avian erythrocytes, and is also found in a phenotypically adenylate cyclase-deficient hepatoma cell line. Mixture of AC- S49 membranes, which contain the beta-adrenergic receptor, with a crude detergent-solubilized preparation of the regulatory protein reconstitutes hormone-stimulable adenylate cyclase activity. Binding of the regulatory protein to the membranes is a time- and temperature-dependent process that requires an activating ligand of the adenylate cyclase system [fluoride, Gpp(NH)p]."}
{"id": "PMID:231787", "title": "Processing of common precursor forms of adrenocorticotropin and endorphins in cultures of mouse pituitary cells and in mouse pituitary.", "content": "The initial steps in the processing of the common precursor to adrenocorticotropin (ACTH) and beta-lipotropin (beta-LPH) in mouse pituitary cells (AtT-20) have been investigated. Three forms of the precursor have been resolved by sodium dodecyl sulfate (NaDodSO4) polyacrylamide gel electrophoresis with apparent molecular weights of 29,000, 32,000 and 34,000 (29K, 32K, and 34K ACTH-endorphin). The three precursor forms have a very similar peptide backbone, but their carbohydrate content differs. In particular, a tryptic glycopeptide has been observed in 32K ACTH-endorphin which is not present in 29K ACTH-endorphin and has been identified as a tryptic peptide containing the alpha(22--39) sequence of ACTH. Pulse chase and continuous-labeling studies with radioactive amino acids and sugars suggest that the 29K form is converted to the 32K and 34K forms of the precursor by the addition of carbohydrate. The glycopeptide and pulse chase studies suggest that 29K ACTH-endorphin can either be converted to 4.5K ACTH by proteolytic processing or to 32K ACTH-endorphin by the further addition of carbohydrate.", "contents": "Processing of common precursor forms of adrenocorticotropin and endorphins in cultures of mouse pituitary cells and in mouse pituitary. The initial steps in the processing of the common precursor to adrenocorticotropin (ACTH) and beta-lipotropin (beta-LPH) in mouse pituitary cells (AtT-20) have been investigated. Three forms of the precursor have been resolved by sodium dodecyl sulfate (NaDodSO4) polyacrylamide gel electrophoresis with apparent molecular weights of 29,000, 32,000 and 34,000 (29K, 32K, and 34K ACTH-endorphin). The three precursor forms have a very similar peptide backbone, but their carbohydrate content differs. In particular, a tryptic glycopeptide has been observed in 32K ACTH-endorphin which is not present in 29K ACTH-endorphin and has been identified as a tryptic peptide containing the alpha(22--39) sequence of ACTH. Pulse chase and continuous-labeling studies with radioactive amino acids and sugars suggest that the 29K form is converted to the 32K and 34K forms of the precursor by the addition of carbohydrate. The glycopeptide and pulse chase studies suggest that 29K ACTH-endorphin can either be converted to 4.5K ACTH by proteolytic processing or to 32K ACTH-endorphin by the further addition of carbohydrate."}
{"id": "PMID:231789", "title": "Self-administration of delta 9-tetrahydrocannabinol by rats.", "content": "The present study examines the dose-response pattern of delta 9-tetrahydrocannabinol self-injection in naive rats at 80% reduced body weight and 100% body weight, both conditions with a fixed-time 1 min (FT-1) food delivery schedule. The results indicated that food deprived animals tested on a FT-1 min schedule self-injected low doses of delta 9-THC at a higher rate than those animals at 100% body weight and on a FT-1 min schedule. Animals at 80% reduced body weight without a schedule did not differ from rats self-injecting delta 9-THC at free feeding situation. These findings suggest that rats without previous history of drug dependence self-administer low doses of delta 9-THC and that the interaction between the food deprivation state and the environmental contingencies introduced by a FT-1 min schedule is a critical variable in the acquisition period.", "contents": "Self-administration of delta 9-tetrahydrocannabinol by rats. The present study examines the dose-response pattern of delta 9-tetrahydrocannabinol self-injection in naive rats at 80% reduced body weight and 100% body weight, both conditions with a fixed-time 1 min (FT-1) food delivery schedule. The results indicated that food deprived animals tested on a FT-1 min schedule self-injected low doses of delta 9-THC at a higher rate than those animals at 100% body weight and on a FT-1 min schedule. Animals at 80% reduced body weight without a schedule did not differ from rats self-injecting delta 9-THC at free feeding situation. These findings suggest that rats without previous history of drug dependence self-administer low doses of delta 9-THC and that the interaction between the food deprivation state and the environmental contingencies introduced by a FT-1 min schedule is a critical variable in the acquisition period."}
{"id": "PMID:231790", "title": "Effect of autoanalgesia on CNS enkephalin receptors.", "content": "Fear conditioning to foot shock (15 sec/day, 12 days) elicited autoanalgesia in 10 male (Sprague-Dawley) rats, while 17 non-shock control rats exhibited no analgesia as measured by the tail-flick assay. The binding of 3H-leu-enkephalin to synaptosomal preparations isolated from fear conditioned (experimental) and control animals was analyzed. At leu-enkephalin concentrations of 10(-9) M or less, both synaptosomal preparations demonstrated high affinity binding with dissociation constants on the order of 10(-10). Binding of leu-enkephalin could not be displaced by a hundred-fold excess of naloxone at leu-enkephalin concentrations less than 10(-9) M. However, the ability of naloxone to compete with leu-enkephalin for binding sites progressively increased at concentrations greater than 10(-9) M leu-enkephalin. At these ligand concentrations, the competition of naloxone for leu-enkephalin binding sites was more dramatic in the control than in the experimental animals. These data support the existence of two classes of receptors for leu-enkephalin, one of which is not blocked by opiate antagonists. Furthermore, changes in binding capacity associated with autoanalgesia produced by conditioned fear are consistent with the hypothesis of endogenous release of opiate-like peptides in response to stress.", "contents": "Effect of autoanalgesia on CNS enkephalin receptors. Fear conditioning to foot shock (15 sec/day, 12 days) elicited autoanalgesia in 10 male (Sprague-Dawley) rats, while 17 non-shock control rats exhibited no analgesia as measured by the tail-flick assay. The binding of 3H-leu-enkephalin to synaptosomal preparations isolated from fear conditioned (experimental) and control animals was analyzed. At leu-enkephalin concentrations of 10(-9) M or less, both synaptosomal preparations demonstrated high affinity binding with dissociation constants on the order of 10(-10). Binding of leu-enkephalin could not be displaced by a hundred-fold excess of naloxone at leu-enkephalin concentrations less than 10(-9) M. However, the ability of naloxone to compete with leu-enkephalin for binding sites progressively increased at concentrations greater than 10(-9) M leu-enkephalin. At these ligand concentrations, the competition of naloxone for leu-enkephalin binding sites was more dramatic in the control than in the experimental animals. These data support the existence of two classes of receptors for leu-enkephalin, one of which is not blocked by opiate antagonists. Furthermore, changes in binding capacity associated with autoanalgesia produced by conditioned fear are consistent with the hypothesis of endogenous release of opiate-like peptides in response to stress."}
{"id": "PMID:231794", "title": "Disease of the vertebral basilar system.", "content": "Patients with acute bilateral, crossed, or multisystem neuroanatomic symptoms associated with cranial nerve palsies may have vertebral basilar system disease. Surgically correctable lesions are usually not found in these patients, and medical therapy with short-term anticoagulation or antiplatelet agglutination may be prescribed in those patients with transient ischemic attacks or progressing stroke.", "contents": "Disease of the vertebral basilar system. Patients with acute bilateral, crossed, or multisystem neuroanatomic symptoms associated with cranial nerve palsies may have vertebral basilar system disease. Surgically correctable lesions are usually not found in these patients, and medical therapy with short-term anticoagulation or antiplatelet agglutination may be prescribed in those patients with transient ischemic attacks or progressing stroke."}
{"id": "PMID:231796", "title": "[Observations on the behaviour of anti-HAV antibodies (author's transl)].", "content": "The behaviour of anti-HAV antibodies was studied in the following conditions: a) a sample group of 2645 subjects from a healthy population; b) a group of 32 subjects with previous HB-Ag negative viral hepatitis; c) 12 cases of acute virus A hepatitis; d) a group of 18 anti-HAV positive women at the end of their pregnancies the antibodies were thus also studied in the funicular blood and in the newborn babies. The results showed: a) high reactivity (78%) of the healthy population to anti-HAV's; b) the possibility of an a posteriori diagnosis of virus A hepatitis in the presence of serology, negative for B type hepatitis, and positive for the anti-HAV's but with a titre higher than 1:200; c) the possibility of a serological diagnosis of acute virus A hepatitis in the presence of serology, negative for B type hepatitis and positive for the anti-HAV's with high and progressively increasing titre; d) the possibility of anti-HAV antibodies passing from mother to foetus, and the rapid elimination of the antibodies by the newborn baby within a month of his birth.", "contents": "[Observations on the behaviour of anti-HAV antibodies (author's transl)]. The behaviour of anti-HAV antibodies was studied in the following conditions: a) a sample group of 2645 subjects from a healthy population; b) a group of 32 subjects with previous HB-Ag negative viral hepatitis; c) 12 cases of acute virus A hepatitis; d) a group of 18 anti-HAV positive women at the end of their pregnancies the antibodies were thus also studied in the funicular blood and in the newborn babies. The results showed: a) high reactivity (78%) of the healthy population to anti-HAV's; b) the possibility of an a posteriori diagnosis of virus A hepatitis in the presence of serology, negative for B type hepatitis, and positive for the anti-HAV's but with a titre higher than 1:200; c) the possibility of a serological diagnosis of acute virus A hepatitis in the presence of serology, negative for B type hepatitis and positive for the anti-HAV's with high and progressively increasing titre; d) the possibility of anti-HAV antibodies passing from mother to foetus, and the rapid elimination of the antibodies by the newborn baby within a month of his birth."}
{"id": "PMID:231797", "title": "[Protective effect in the serum of rabbits inoculated with BHK-21 cells infected with foot-and-mouth disease virus].", "content": "The present investigation was developed to determine the presence of protecting effects in the serum of rabbits inoculated with BHK 21 cells infected with foot-and-mouth disease virus, subtype C2. The rabbits received 252 mg. of antigens harvested 60, 65, 75, 90, 120 and 210 minutes post infection. These antigens were inactivated with two procedure: formaldehyde 0.015% and beta-propiolactone 0.2% and were inyected with incomplete Freund's adjuvant; the last inoculations were given with live antigen without adjuvant. The immunization period lasted approximately for six months. A seroprotection test in suckling mice was performed with each antiserum. The antisera corresponding to 75, 120 and 210 minutes post infection had protector effect. But antisera obtained with BHK cells at 75 minutes showed highly significant protective effect, as compared with the other two sera.", "contents": "[Protective effect in the serum of rabbits inoculated with BHK-21 cells infected with foot-and-mouth disease virus]. The present investigation was developed to determine the presence of protecting effects in the serum of rabbits inoculated with BHK 21 cells infected with foot-and-mouth disease virus, subtype C2. The rabbits received 252 mg. of antigens harvested 60, 65, 75, 90, 120 and 210 minutes post infection. These antigens were inactivated with two procedure: formaldehyde 0.015% and beta-propiolactone 0.2% and were inyected with incomplete Freund's adjuvant; the last inoculations were given with live antigen without adjuvant. The immunization period lasted approximately for six months. A seroprotection test in suckling mice was performed with each antiserum. The antisera corresponding to 75, 120 and 210 minutes post infection had protector effect. But antisera obtained with BHK cells at 75 minutes showed highly significant protective effect, as compared with the other two sera."}
{"id": "PMID:231800", "title": "[Subtypes of foot-and-mouth disease virus type A. Genetic markers of clones obtained from 4 strains isolated in Argentina between 1961 and 1970].", "content": "The results obtained studying the genetic markers g, t and rtc of different clones of subtypes of foot-and-mouth disease virus type A are presented in this paper. The subtypes were isolated during outbreaks of foot and mouth disease in Argentine. No significative differences among the subtypes were observed with the t marker. For the other markers, the results seem to indicate a gradual change related with the serological variation. Because of their sensibility to guanidine hidrochloride, it is possible to conclude that the studied clones do not belong to the so called European strains.", "contents": "[Subtypes of foot-and-mouth disease virus type A. Genetic markers of clones obtained from 4 strains isolated in Argentina between 1961 and 1970]. The results obtained studying the genetic markers g, t and rtc of different clones of subtypes of foot-and-mouth disease virus type A are presented in this paper. The subtypes were isolated during outbreaks of foot and mouth disease in Argentine. No significative differences among the subtypes were observed with the t marker. For the other markers, the results seem to indicate a gradual change related with the serological variation. Because of their sensibility to guanidine hidrochloride, it is possible to conclude that the studied clones do not belong to the so called European strains."}
{"id": "PMID:231807", "title": "Salmefamol and salbutamol. An experimental comparative study of their action on tracheal and bronchial smooth muscles.", "content": "An experimental comparative study has been undertaken to evaluate the action of salmefamol and salbutamol, two sympathomimetic drugs specific for the beta-receptors, on tracheal and bronchial smooth muscles. Salmefamol showed a more intense, longer-lasting beta-adrenergic activity than salbutamol did.", "contents": "Salmefamol and salbutamol. An experimental comparative study of their action on tracheal and bronchial smooth muscles. An experimental comparative study has been undertaken to evaluate the action of salmefamol and salbutamol, two sympathomimetic drugs specific for the beta-receptors, on tracheal and bronchial smooth muscles. Salmefamol showed a more intense, longer-lasting beta-adrenergic activity than salbutamol did."}
{"id": "PMID:231808", "title": "[On the pathogenesis of isocyanate-induced asthma].", "content": "3 asthmatic patients, occupationally exposed to vapors of toluylene diisocyanate (TDI), responded with a moderate to strong elevation of airway resistance up to the 26th h after inhalation challenge by 0.006--0.02 ppm TDI. No changes in chest radiographs and in DLCO were found. In none of the patients' sera, isocyanate-specific antibodies could be detected by RAST and Ouchterlony test. Change of job resulted in one case in an immediate interruption of the asthmatic symptoms, whereas in 2 patients recovery was slow over a period of 3 to 8 months and not complete. Our investigations suggest a toxic effect of isocyanates, which depends on their concentrations, and an important pharmacological reaction; but, up to now, there were no signs of allergic mechanisms.", "contents": "[On the pathogenesis of isocyanate-induced asthma]. 3 asthmatic patients, occupationally exposed to vapors of toluylene diisocyanate (TDI), responded with a moderate to strong elevation of airway resistance up to the 26th h after inhalation challenge by 0.006--0.02 ppm TDI. No changes in chest radiographs and in DLCO were found. In none of the patients' sera, isocyanate-specific antibodies could be detected by RAST and Ouchterlony test. Change of job resulted in one case in an immediate interruption of the asthmatic symptoms, whereas in 2 patients recovery was slow over a period of 3 to 8 months and not complete. Our investigations suggest a toxic effect of isocyanates, which depends on their concentrations, and an important pharmacological reaction; but, up to now, there were no signs of allergic mechanisms."}
{"id": "PMID:231809", "title": "Efficacy, safety and hypothalamic-pituitary-adrenal axis function in patients with asthma treated with cloprednol.", "content": "Cloprednol was tested in 25 patients with chronic reversible bronchial obstruction, with respect to changes in hypothalamic-pituitary-adrenal (HPA) axis function and its efficacy on their clinical asthma. Patients were treated by a single morning dose for a 6-month period. The HPA axis function as estimated by fasting plasma cortisol levels did not show any significant changes, but adrenal response, assessed by ACTH stimulation test, was found slightly less at 6 months than at 3 months and at baseline. Pulmonary function tests--FEV1 and Raw--showed some improvement during the trial period. The score of respiratory complaints and symptoms, as well as the subjective status of the patients, showed a trend towards improvement. No significant side effects were observed.", "contents": "Efficacy, safety and hypothalamic-pituitary-adrenal axis function in patients with asthma treated with cloprednol. Cloprednol was tested in 25 patients with chronic reversible bronchial obstruction, with respect to changes in hypothalamic-pituitary-adrenal (HPA) axis function and its efficacy on their clinical asthma. Patients were treated by a single morning dose for a 6-month period. The HPA axis function as estimated by fasting plasma cortisol levels did not show any significant changes, but adrenal response, assessed by ACTH stimulation test, was found slightly less at 6 months than at 3 months and at baseline. Pulmonary function tests--FEV1 and Raw--showed some improvement during the trial period. The score of respiratory complaints and symptoms, as well as the subjective status of the patients, showed a trend towards improvement. No significant side effects were observed."}
{"id": "PMID:231812", "title": "[Association of acquired polyagglutinabilities of types T and B. An observation].", "content": "Although T and acquired B polyagglutinabilities are not exceptional, simultaneous occurence of the two types is a rarer phenomenon. Ten days after an open heart surgery operation, the patient, age 55, had an infectious syndrom : two strains, Clostridium perfringens and Peptococcus variabilis were isolated. Simultaneously, her red cells were found to be polyagglutinable. The association of T and acquired B polyagglutinabilities could be demonstrated by serological studies of the patient's red cells, and by in vitro transformation of normal red cells using culture supernatants obtained from the two isolated strains.", "contents": "[Association of acquired polyagglutinabilities of types T and B. An observation]. Although T and acquired B polyagglutinabilities are not exceptional, simultaneous occurence of the two types is a rarer phenomenon. Ten days after an open heart surgery operation, the patient, age 55, had an infectious syndrom : two strains, Clostridium perfringens and Peptococcus variabilis were isolated. Simultaneously, her red cells were found to be polyagglutinable. The association of T and acquired B polyagglutinabilities could be demonstrated by serological studies of the patient's red cells, and by in vitro transformation of normal red cells using culture supernatants obtained from the two isolated strains."}
{"id": "PMID:231818", "title": "Hodgkin's disease and infectious mononucleosis.", "content": "Sequential sero-positive infectious mononucleosis is described in 3 sibs, 2 of whom subsequently developed Hodgkin's disease. EB virus antibodies were present in the serum of both cases.", "contents": "Hodgkin's disease and infectious mononucleosis. Sequential sero-positive infectious mononucleosis is described in 3 sibs, 2 of whom subsequently developed Hodgkin's disease. EB virus antibodies were present in the serum of both cases."}
{"id": "PMID:231819", "title": "Angiotensin converting enzyme. III. Changes in serum level as an indicator of disease activity in untreated sarcoidosis.", "content": "The activity of serum angiotensin converting enzyme (ACE) was repeatedly measured together with serum lysozyme (LZM) in patients with untreated sarcoidosis. Changes in the clinical picture were registered using chest X-ray, forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO) and appearance of extrapulmonary lesions. During a clinically unchanged period the highest ACE activity and the corresponding LZM value (not the highest value) were used for the calculation. A statistically significant change in ACE was noted when a normal chest X-ray changed to a stage II lesion or vice versa, and when a signficant change in FVC occurred. All other changes were insignificant. On the other hand, statistically significant changes in ACE were found during stable periods according to chest X-ray, FVC or DLCO. ACE is frequently elevated in serum of patients with active sarcoidosis. The fluctuations in activity mostly parallel the clinical course of the disease. The behaviour and metabolism of the enzyme need further investigation. An increased concentration of serum LZM is frequent in patients with active sarcoidosis. The highest LZM values are not always seen simultaneously with the highest ACE values, indicating that they probably express different dimensions of the disturbances in the sarcoid granuloma.", "contents": "Angiotensin converting enzyme. III. Changes in serum level as an indicator of disease activity in untreated sarcoidosis. The activity of serum angiotensin converting enzyme (ACE) was repeatedly measured together with serum lysozyme (LZM) in patients with untreated sarcoidosis. Changes in the clinical picture were registered using chest X-ray, forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO) and appearance of extrapulmonary lesions. During a clinically unchanged period the highest ACE activity and the corresponding LZM value (not the highest value) were used for the calculation. A statistically significant change in ACE was noted when a normal chest X-ray changed to a stage II lesion or vice versa, and when a signficant change in FVC occurred. All other changes were insignificant. On the other hand, statistically significant changes in ACE were found during stable periods according to chest X-ray, FVC or DLCO. ACE is frequently elevated in serum of patients with active sarcoidosis. The fluctuations in activity mostly parallel the clinical course of the disease. The behaviour and metabolism of the enzyme need further investigation. An increased concentration of serum LZM is frequent in patients with active sarcoidosis. The highest LZM values are not always seen simultaneously with the highest ACE values, indicating that they probably express different dimensions of the disturbances in the sarcoid granuloma."}
{"id": "PMID:231820", "title": "Angiotensin converting enzyme. IV. Changes in serum activity and in lysozyme concentrations as indicators of the course of untreated sarcoidosis.", "content": "The mean values of serum angiotensin-converting enzyme (ACE) activities and lysozyme (LZM) concentrations measured during different phases of sarcoidosis coincided well with the clinical evaluation of the state of the disease. However, both enzymes, especially LZM, decreased before improvement was detected. Changes in these enzymes were in accord with the simultaneous clinical development in three fourths of cases. Incompatibility between clinical observations apnd LZM fluctuations was most frequently seen during active stable or inactive disease. LZM often decreased during the active stable phase and fluctuated irregularly during inactive disease. During the former phase LZM decrements possibly reflect decreasing activity of granulomatous macrophages and, in fact, precede detectable improvement. During inactive disease, on the other hand, cells were not connected with the disease process dominate LZM production. ACE changes paralleled the clinical development more often than corresponding LZM changes during stable sarcoidosis. This may have been misleading and due to a delayed reaction of serum ACE, compared with LZM, inreflecting the activity of granylomatous cells. This delayed reaction was also observed in connection with erythema nodosum. Stable ACE activity during inactive sarcoidosis indicated the usefulness of measurements when trying to predict a relapse. We conclude that ACE may be a secondary feature of sarcoidosis rather than a primary funtion of macrophage activity.", "contents": "Angiotensin converting enzyme. IV. Changes in serum activity and in lysozyme concentrations as indicators of the course of untreated sarcoidosis. The mean values of serum angiotensin-converting enzyme (ACE) activities and lysozyme (LZM) concentrations measured during different phases of sarcoidosis coincided well with the clinical evaluation of the state of the disease. However, both enzymes, especially LZM, decreased before improvement was detected. Changes in these enzymes were in accord with the simultaneous clinical development in three fourths of cases. Incompatibility between clinical observations apnd LZM fluctuations was most frequently seen during active stable or inactive disease. LZM often decreased during the active stable phase and fluctuated irregularly during inactive disease. During the former phase LZM decrements possibly reflect decreasing activity of granulomatous macrophages and, in fact, precede detectable improvement. During inactive disease, on the other hand, cells were not connected with the disease process dominate LZM production. ACE changes paralleled the clinical development more often than corresponding LZM changes during stable sarcoidosis. This may have been misleading and due to a delayed reaction of serum ACE, compared with LZM, inreflecting the activity of granylomatous cells. This delayed reaction was also observed in connection with erythema nodosum. Stable ACE activity during inactive sarcoidosis indicated the usefulness of measurements when trying to predict a relapse. We conclude that ACE may be a secondary feature of sarcoidosis rather than a primary funtion of macrophage activity."}
{"id": "PMID:231821", "title": "Determination of quartz on membrane filters by X-ray diffraction.", "content": "An X-ray diffraction method is described for the quantitative determination of quartz in dust samples. The analysis was done directly on a collecting cellulose ester membrane filter of the type used in an air sampler. Quantitation was achieved by the measurement of the quartz line intensities with a digital integrator and by the comparison of these values with those measured from calibration standards prepared on similar filters with water suspensions. The overall precision of the procedure was 8%. When the method was applied to foundry dusts, the accuracy of the quartz analysis was fou,d to be within 10% at the 1- to 10-mg level of total loading. The detection limit for quartz was below 0.1 mg.", "contents": "Determination of quartz on membrane filters by X-ray diffraction. An X-ray diffraction method is described for the quantitative determination of quartz in dust samples. The analysis was done directly on a collecting cellulose ester membrane filter of the type used in an air sampler. Quantitation was achieved by the measurement of the quartz line intensities with a digital integrator and by the comparison of these values with those measured from calibration standards prepared on similar filters with water suspensions. The overall precision of the procedure was 8%. When the method was applied to foundry dusts, the accuracy of the quartz analysis was fou,d to be within 10% at the 1- to 10-mg level of total loading. The detection limit for quartz was below 0.1 mg."}
{"id": "PMID:231822", "title": "[Coronary atherosclerosis and serum lipoproteins].", "content": "VLDL triglycerides were increased both in obese patients and obese controls. In lean CHD patients the VLDL triglycerides were higher than in lean controls but lower than in obese CHD patients. CHD patients had lower HDL cholesterol than controls. The lowest HDL cholesterol was observed when VLDL triglycerides were high in both CHD patients and controls. However, the differences in HDL cholesterol between CHD patients and controls with low VLDL triglycerides were more marked. It appears that factors other than VLDL triglycerides may also contribute to the low HDL cholesterol observed in CHD patients. Serum cholesterol and triglycerides did not reflect the more subtle changes occurring in the lipoprotein lipids of CHD patients.", "contents": "[Coronary atherosclerosis and serum lipoproteins]. VLDL triglycerides were increased both in obese patients and obese controls. In lean CHD patients the VLDL triglycerides were higher than in lean controls but lower than in obese CHD patients. CHD patients had lower HDL cholesterol than controls. The lowest HDL cholesterol was observed when VLDL triglycerides were high in both CHD patients and controls. However, the differences in HDL cholesterol between CHD patients and controls with low VLDL triglycerides were more marked. It appears that factors other than VLDL triglycerides may also contribute to the low HDL cholesterol observed in CHD patients. Serum cholesterol and triglycerides did not reflect the more subtle changes occurring in the lipoprotein lipids of CHD patients."}
{"id": "PMID:231823", "title": "[Treatment of smokers by the chirotesist Hermano. 5 year catamnesis].", "content": "A study of a random sample of 532 cigarette smokers was made among the persons treated by the chirothesist Hermano in Seon (Switzerland), who had cured smokers of their nicotine addiction. They were examined immediately befroe the treatment ritual, then 4 months, 1 year and 5 years after the treatment. The patients of the healer were chosen from all the strata of the population. They were heavy smokers with an average of 31 cigarettes smoking rate per day for males and 24 cigarettes per day for females. Four months after the treatment, 40% of the treated persons, 12 months after the treatment 32.5% and 5 years after it 20% of the treated persons were completely freed of recidivism. Another 3.7% did smoke but only sporadically up to 5 years. Two thirds of the patients mentioned a suggestive effect which they consciously registered or which they remembered in the sense that their urge to smoke had diminished partly or disappeared completely thanks to the treatment. The analysis of the dynamics of recidivism showed that apart from its complete absence the cases of partial success in the sense of a moderation of the smoking, or as to a transitional stoppage were only a few. The methodical control of the follow-up study showed that the recidivists showed a lesser readiness to answer during the catamnestic examinations and it is therefore necessary for all the follow-up studies as well as for the comparative therapeutical research to take into consideration the degree of completeness of the catamnestic examination.", "contents": "[Treatment of smokers by the chirotesist Hermano. 5 year catamnesis]. A study of a random sample of 532 cigarette smokers was made among the persons treated by the chirothesist Hermano in Seon (Switzerland), who had cured smokers of their nicotine addiction. They were examined immediately befroe the treatment ritual, then 4 months, 1 year and 5 years after the treatment. The patients of the healer were chosen from all the strata of the population. They were heavy smokers with an average of 31 cigarettes smoking rate per day for males and 24 cigarettes per day for females. Four months after the treatment, 40% of the treated persons, 12 months after the treatment 32.5% and 5 years after it 20% of the treated persons were completely freed of recidivism. Another 3.7% did smoke but only sporadically up to 5 years. Two thirds of the patients mentioned a suggestive effect which they consciously registered or which they remembered in the sense that their urge to smoke had diminished partly or disappeared completely thanks to the treatment. The analysis of the dynamics of recidivism showed that apart from its complete absence the cases of partial success in the sense of a moderation of the smoking, or as to a transitional stoppage were only a few. The methodical control of the follow-up study showed that the recidivists showed a lesser readiness to answer during the catamnestic examinations and it is therefore necessary for all the follow-up studies as well as for the comparative therapeutical research to take into consideration the degree of completeness of the catamnestic examination."}
{"id": "PMID:231825", "title": "[Histological study of the bone marrow in 96 cases of Waldenstrom's macroglobulinemia. An evaluation with clinical, haematological and biological data (author's transl)].", "content": "Bone marrow biopsy in Waldenstrom's macroglobulinemia shows three types of lesions: lympho-plasmocytic and reticular infiltration, which is the most common, reticular infiltration, and aplastic marrow, more seldom. In all cases the reticulinic network is increased and thickened. These lesions are diffuse or nodular. Diffuse infiltration is more severe and has a median duration of 62 months instead of 82 months in nodular infiltration.", "contents": "[Histological study of the bone marrow in 96 cases of Waldenstrom's macroglobulinemia. An evaluation with clinical, haematological and biological data (author's transl)]. Bone marrow biopsy in Waldenstrom's macroglobulinemia shows three types of lesions: lympho-plasmocytic and reticular infiltration, which is the most common, reticular infiltration, and aplastic marrow, more seldom. In all cases the reticulinic network is increased and thickened. These lesions are diffuse or nodular. Diffuse infiltration is more severe and has a median duration of 62 months instead of 82 months in nodular infiltration."}
{"id": "PMID:231826", "title": "[Lymphomas of the spleen and bone marrow lymphoid nodules (author's transl)].", "content": "Many nodular primitive non-Hodgkin's lymphomas of the spleen have a favourable course after splenectomy or chemotherapy. Several observations of this type have been reported in the literature, in which the concept of malignancy is discussed, authors referring to a presarcomatous state or to an idiopathic splenomegaly. The evaluation of the extension of those sarcomas, however, very often show hepatic lesions, and always an increase in the lymphoid marrow nodules. The significance of these nodules is discussed here, with reference to 14 personal observations. These nodules may not always reflect a real extension of the sarcoma to the marrow. From a practical point of view, the presence of lymphoid marrow nodules, when associated with an isolated splenomegaly, is a strong argument to suspect a sarcoma of the spleen, and indicates a splenectomy.", "contents": "[Lymphomas of the spleen and bone marrow lymphoid nodules (author's transl)]. Many nodular primitive non-Hodgkin's lymphomas of the spleen have a favourable course after splenectomy or chemotherapy. Several observations of this type have been reported in the literature, in which the concept of malignancy is discussed, authors referring to a presarcomatous state or to an idiopathic splenomegaly. The evaluation of the extension of those sarcomas, however, very often show hepatic lesions, and always an increase in the lymphoid marrow nodules. The significance of these nodules is discussed here, with reference to 14 personal observations. These nodules may not always reflect a real extension of the sarcoma to the marrow. From a practical point of view, the presence of lymphoid marrow nodules, when associated with an isolated splenomegaly, is a strong argument to suspect a sarcoma of the spleen, and indicates a splenectomy."}
{"id": "PMID:231827", "title": "[Non secretary plasma cell leukemia with intracytoplasmic kappa light chains (author's transl)].", "content": "A 53 years old female patient with plasma cell leukemia (more than 90% plasma cells in the peripheral blood, and an absolute plasma cell count reaching 147,000/mm3) is described. Electrophoresis and immunoelectrophoresis of serum and concentrated urine did not reveal any paraprotein. No surface immunoglobin has been detected on plasma cell cytoplasmic membranes. The presence of intracytoplasmic kappa light chains has been demonstrated by immunofluorescence and electron microscopy using the immunoperoxydase technique.", "contents": "[Non secretary plasma cell leukemia with intracytoplasmic kappa light chains (author's transl)]. A 53 years old female patient with plasma cell leukemia (more than 90% plasma cells in the peripheral blood, and an absolute plasma cell count reaching 147,000/mm3) is described. Electrophoresis and immunoelectrophoresis of serum and concentrated urine did not reveal any paraprotein. No surface immunoglobin has been detected on plasma cell cytoplasmic membranes. The presence of intracytoplasmic kappa light chains has been demonstrated by immunofluorescence and electron microscopy using the immunoperoxydase technique."}
{"id": "PMID:231828", "title": "[Adult medulloblastomas. Clinical, anatomical and therapeutical study on seventeen cases (author's transl)].", "content": "Medulloblastoma is classically a childhood tumor, but one third of the cases occurs in adulthood. 17 adult cases are reported here (12 men, 5 women). The average age was 26 years 6 m (from 16 to 47 years). Pre-surgical clinical course is shorter before 30 years (7 months) than after (up to 24 months). Initial symptoms were intracranial hypertension with signs of lateralisation in 2:3 of the cases (cranial nerve and pontocerebellar syndroms). Vertebral angiography, scintigraphy, tomodensitometry helped to the diagnosis. Morphologically, two variants of tumors were found: soft and infiltrative classical medulloblastoma (12 cases) and desmoplastic medulloblastoma which was firmer and better limited (5 cases). The treatment consisted of a surgical removal, as complete as possible, then of an entire neuraxis radiation. Three operated patients died before 6 weeks. Among the 14 other cases, six patients are still alive three years, four other, five years and one, 22 years after the operation. This histological type was of no influence on the post-operative course. Remote metastasis were noted in cauda equina (3 cases), in spinal cord (1 case), in bones and lymphatic nodes (3 cases).", "contents": "[Adult medulloblastomas. Clinical, anatomical and therapeutical study on seventeen cases (author's transl)]. Medulloblastoma is classically a childhood tumor, but one third of the cases occurs in adulthood. 17 adult cases are reported here (12 men, 5 women). The average age was 26 years 6 m (from 16 to 47 years). Pre-surgical clinical course is shorter before 30 years (7 months) than after (up to 24 months). Initial symptoms were intracranial hypertension with signs of lateralisation in 2:3 of the cases (cranial nerve and pontocerebellar syndroms). Vertebral angiography, scintigraphy, tomodensitometry helped to the diagnosis. Morphologically, two variants of tumors were found: soft and infiltrative classical medulloblastoma (12 cases) and desmoplastic medulloblastoma which was firmer and better limited (5 cases). The treatment consisted of a surgical removal, as complete as possible, then of an entire neuraxis radiation. Three operated patients died before 6 weeks. Among the 14 other cases, six patients are still alive three years, four other, five years and one, 22 years after the operation. This histological type was of no influence on the post-operative course. Remote metastasis were noted in cauda equina (3 cases), in spinal cord (1 case), in bones and lymphatic nodes (3 cases)."}
{"id": "PMID:231829", "title": "[Circulating immune complexes in rheumatoid arthritis. Results of a personal research (author's transl)].", "content": "Using the technic of Pillot and Grangeot (pr\u00e9cipitation by PEG 6,000 at 2.5%, followed radial immuno-diffusion), the authors have detected circulating immune complexes (CIC) 38 times in a group of 55 RA. The presence of CIC is significantly more frequent in sero-positive RA, but without correlation between the concentration of CIC and the positivity rate of Waaler-Rose reaction. There is no correlation between the evolutive state of RA and the presence or the concentration of CIC. The sedimentation rate is, in mean, significantly higher in RA with CIC; but, among these, there is no correlation between sedimentation rate and the concentration of CIC. In the group studied, the CIC are present in all cases of RA with vasculitis or visceral symptoms.", "contents": "[Circulating immune complexes in rheumatoid arthritis. Results of a personal research (author's transl)]. Using the technic of Pillot and Grangeot (pr\u00e9cipitation by PEG 6,000 at 2.5%, followed radial immuno-diffusion), the authors have detected circulating immune complexes (CIC) 38 times in a group of 55 RA. The presence of CIC is significantly more frequent in sero-positive RA, but without correlation between the concentration of CIC and the positivity rate of Waaler-Rose reaction. There is no correlation between the evolutive state of RA and the presence or the concentration of CIC. The sedimentation rate is, in mean, significantly higher in RA with CIC; but, among these, there is no correlation between sedimentation rate and the concentration of CIC. In the group studied, the CIC are present in all cases of RA with vasculitis or visceral symptoms."}
{"id": "PMID:231830", "title": "[Effects of an antiinflammatory drug (diclofenac) in primary chronic glomerulo-nephritis (author's transl)].", "content": "Chronic Glomerulo-Nephritis (GN) are among nephrologic diseases, frequent and severe. In most of them immunological process are involved. Non stero\u00efdal antiinflammatory drugs are able to reduce proteinuria, mainly in Membrano-Proliferative GN and IgA Mesengial GN. A protracted administration is necessary for proteinuria reappeared when treatment is interrupted. With long term administration renal prognosis is improved and severe renal insufficiency delayed. Among active antiinflammatory drugs (indometacine, ketoprofen, diclofenac, flurbiprofen, etc.) diclofenac is one of the best tolerated.", "contents": "[Effects of an antiinflammatory drug (diclofenac) in primary chronic glomerulo-nephritis (author's transl)]. Chronic Glomerulo-Nephritis (GN) are among nephrologic diseases, frequent and severe. In most of them immunological process are involved. Non stero\u00efdal antiinflammatory drugs are able to reduce proteinuria, mainly in Membrano-Proliferative GN and IgA Mesengial GN. A protracted administration is necessary for proteinuria reappeared when treatment is interrupted. With long term administration renal prognosis is improved and severe renal insufficiency delayed. Among active antiinflammatory drugs (indometacine, ketoprofen, diclofenac, flurbiprofen, etc.) diclofenac is one of the best tolerated."}
{"id": "PMID:231831", "title": "[Pituitary investigations in idiopathic haemochromatosis (author's transl)].", "content": "Twelve patients with idiopathic hemochromatosis have been studied. Hypogonadotropic hypogonadism with normal prolactin appears to be a most constant finding. Other hypophysal functions are preserved. A rapid exploration of such patients with LHRH-TRH and insulin tolerance test is proposed.", "contents": "[Pituitary investigations in idiopathic haemochromatosis (author's transl)]. Twelve patients with idiopathic hemochromatosis have been studied. Hypogonadotropic hypogonadism with normal prolactin appears to be a most constant finding. Other hypophysal functions are preserved. A rapid exploration of such patients with LHRH-TRH and insulin tolerance test is proposed."}
{"id": "PMID:231832", "title": "[Value of radiological examination in patients with pheochromocytoma. Results in four cases (author's transl)].", "content": "The authors report 4 cases of pheochromocytoma and analyse the interest of the different x ray examinations. The authors show the interest of angiography, particularly selective angiography, for small tumors, ectopic and multiple abdominal localisations, and metastases. The benign or malignant nature of the tumor, in the absence of metastases, is difficult to assess by x ray examinations alone.", "contents": "[Value of radiological examination in patients with pheochromocytoma. Results in four cases (author's transl)]. The authors report 4 cases of pheochromocytoma and analyse the interest of the different x ray examinations. The authors show the interest of angiography, particularly selective angiography, for small tumors, ectopic and multiple abdominal localisations, and metastases. The benign or malignant nature of the tumor, in the absence of metastases, is difficult to assess by x ray examinations alone."}
{"id": "PMID:231834", "title": "[Quantitative study of the medullar fibrosis in 84 cases of idiopathic myeloid splenomegaly (author's transl)].", "content": "84 bone marrow biopsies were analysed by quantification methods with Classimat. The initial diagnosis was: idiopathic myelofibrosis with splenomegaly. A previous study divided the patients among three categories, according to the classification in three progressive stages of the bone marrow disease. The quantitative lecture was done after reticulin coloration, \"in blind\", and on several biopsies from the same patient. The results show good correlation with classical histologic methods. The quantitative measure of fibrosis is already important as soon as the first stages of the disease. Correlations with prognosis are more difficult to define.", "contents": "[Quantitative study of the medullar fibrosis in 84 cases of idiopathic myeloid splenomegaly (author's transl)]. 84 bone marrow biopsies were analysed by quantification methods with Classimat. The initial diagnosis was: idiopathic myelofibrosis with splenomegaly. A previous study divided the patients among three categories, according to the classification in three progressive stages of the bone marrow disease. The quantitative lecture was done after reticulin coloration, \"in blind\", and on several biopsies from the same patient. The results show good correlation with classical histologic methods. The quantitative measure of fibrosis is already important as soon as the first stages of the disease. Correlations with prognosis are more difficult to define."}
{"id": "PMID:231833", "title": "[Treatment of headaches in general practice. A therapeutic study (author's transl)].", "content": "A therapeutic study was conducted by practitioners working in a group practice, to evaluate the activity of tiapride in treating headaches, over a period of 1 year. The results were satisfactory in 60.6% of cases, especially in patients with headaches of psychogenic or digestive origin. The dosage was 150 to 200 mg orally, and the product was well tolerated apart from somnolence which was noted in about 1 case out of 4.", "contents": "[Treatment of headaches in general practice. A therapeutic study (author's transl)]. A therapeutic study was conducted by practitioners working in a group practice, to evaluate the activity of tiapride in treating headaches, over a period of 1 year. The results were satisfactory in 60.6% of cases, especially in patients with headaches of psychogenic or digestive origin. The dosage was 150 to 200 mg orally, and the product was well tolerated apart from somnolence which was noted in about 1 case out of 4."}
{"id": "PMID:231836", "title": "[Sideroblastic anemia in a multiple myeloma treated by melphalan (author's transl)].", "content": "A case of sideroblastic anemia arised in multiple myeloma is related. Eighteen cases of literature are studied. This evolution usually appears in old and remitted myeloma. The pathogeny of the sideroblastic anemia is unknown, and possibly related to leukemia complicating multiple myeloma.", "contents": "[Sideroblastic anemia in a multiple myeloma treated by melphalan (author's transl)]. A case of sideroblastic anemia arised in multiple myeloma is related. Eighteen cases of literature are studied. This evolution usually appears in old and remitted myeloma. The pathogeny of the sideroblastic anemia is unknown, and possibly related to leukemia complicating multiple myeloma."}
{"id": "PMID:231835", "title": "[Porcelain gallbladder and cancer (author's transl)].", "content": "The porcelain gallbladder is a rare entity. It reaches especially the old woman. Most of the porcelain gallbladders have a great clinical latence. A cancer of the gallbladder exists in eleven per cent of the cases: this justifies a systematic cholecystectomy of the calcified gallbladders, even if they are asymptomatic. Another digestive cancer exists in nine per cent of the cases. Three personal observations of porcelain gallbladder which are associated with a cancer are described: they confirm the facts of the literature.", "contents": "[Porcelain gallbladder and cancer (author's transl)]. The porcelain gallbladder is a rare entity. It reaches especially the old woman. Most of the porcelain gallbladders have a great clinical latence. A cancer of the gallbladder exists in eleven per cent of the cases: this justifies a systematic cholecystectomy of the calcified gallbladders, even if they are asymptomatic. Another digestive cancer exists in nine per cent of the cases. Three personal observations of porcelain gallbladder which are associated with a cancer are described: they confirm the facts of the literature."}
{"id": "PMID:231842", "title": "Preliminary report on an unidentified virus from infantile myocarditis.", "content": "A preliminary report on an unidentified virus from two cases of infantile myocarditis is presented. The virus isolated from two separate occasions showed characteristics of an enterovirus. The significance of this virus in its association with infantile myocarditis requires further investigation.", "contents": "Preliminary report on an unidentified virus from infantile myocarditis. A preliminary report on an unidentified virus from two cases of infantile myocarditis is presented. The virus isolated from two separate occasions showed characteristics of an enterovirus. The significance of this virus in its association with infantile myocarditis requires further investigation."}
{"id": "PMID:231837", "title": "[Acute tuberculous meningitis in children. A report on 4 cases (author's transl)].", "content": "Four children were treated for acute tuberculous meningitis. One child died and 2 others were left with severe neurological sequellae. The diagnostic and clinical signs of tuberculous meningitis are reviewed. Treatment includes the administration of an association of INH-rifampicine and ethambutol orally, or INH-ethambutol-ethionamide intravenously when oral administration is impossible. Intrathecal injections of rifamycine SV can be given for acute forms. Corticoids have only one indication: intracranial hypertension with cerebral edema, which requires surgical decompression if no improvement is obtained. The fact that cases of tuberculous meningitis are still notified, is a justification for early BCG vaccination and regular control of the tuberculin allergic reaction.", "contents": "[Acute tuberculous meningitis in children. A report on 4 cases (author's transl)]. Four children were treated for acute tuberculous meningitis. One child died and 2 others were left with severe neurological sequellae. The diagnostic and clinical signs of tuberculous meningitis are reviewed. Treatment includes the administration of an association of INH-rifampicine and ethambutol orally, or INH-ethambutol-ethionamide intravenously when oral administration is impossible. Intrathecal injections of rifamycine SV can be given for acute forms. Corticoids have only one indication: intracranial hypertension with cerebral edema, which requires surgical decompression if no improvement is obtained. The fact that cases of tuberculous meningitis are still notified, is a justification for early BCG vaccination and regular control of the tuberculin allergic reaction."}
{"id": "PMID:231839", "title": "[Duodenal ulcer and pyloric micro-gastrinoma. A report of one case (author's transl)].", "content": "We report a case of micro-gastrinoma associated with a duodenal ulcer. This ulcer was severe and a gastrectomy (Finsterer) was performed. Pathologic examination showed a \"carcinoid islet cell-tumor\" with argyrophil granules in the cells' cytoplasme and ultrastructural studies confirmed neurosecretory granules with dense central core. Using the immunofluorescence and immunoperoxydase technic with several anti sera against polypeptide hormones we were able to show it was a pure gastrinoma. We presume this association is a new entity in gastrin-cells pathology.", "contents": "[Duodenal ulcer and pyloric micro-gastrinoma. A report of one case (author's transl)]. We report a case of micro-gastrinoma associated with a duodenal ulcer. This ulcer was severe and a gastrectomy (Finsterer) was performed. Pathologic examination showed a \"carcinoid islet cell-tumor\" with argyrophil granules in the cells' cytoplasme and ultrastructural studies confirmed neurosecretory granules with dense central core. Using the immunofluorescence and immunoperoxydase technic with several anti sera against polypeptide hormones we were able to show it was a pure gastrinoma. We presume this association is a new entity in gastrin-cells pathology."}
{"id": "PMID:231838", "title": "[Extensive scabies in a baby (author's transl)].", "content": "The authors are reporting a new case of widespread scabies in a baby. They take this opportunity to emphasize on the atypical erythematous and excoriated papular rash which sometimes may be vesicular and hyper-keratotic. This widespread eruption may mimic generalised dermatitis, pustular psoriasis and even histiocytosis X. They also underline importancy of longlasting ointment with fluorinated steroid being responsible for this widespread eruption.", "contents": "[Extensive scabies in a baby (author's transl)]. The authors are reporting a new case of widespread scabies in a baby. They take this opportunity to emphasize on the atypical erythematous and excoriated papular rash which sometimes may be vesicular and hyper-keratotic. This widespread eruption may mimic generalised dermatitis, pustular psoriasis and even histiocytosis X. They also underline importancy of longlasting ointment with fluorinated steroid being responsible for this widespread eruption."}
{"id": "PMID:231840", "title": "[Functional renal failure (FRF) in cirrhosis (author's transl)].", "content": "Frequent complication of advanced cirrhosis, spontaneous or in response to different causes, FRF is chiefly characterized by hyponatraemia, progressive azotaemia, hyperkalaemia and severe oliguria. Its functional nature is proved but its mechanism remains doubtful: it may be due to decreased \"effective\" plasma volume or renal arteriolar constriction. Its treatment is disappointing and in spite of new technics, gives only transitory improvements.", "contents": "[Functional renal failure (FRF) in cirrhosis (author's transl)]. Frequent complication of advanced cirrhosis, spontaneous or in response to different causes, FRF is chiefly characterized by hyponatraemia, progressive azotaemia, hyperkalaemia and severe oliguria. Its functional nature is proved but its mechanism remains doubtful: it may be due to decreased \"effective\" plasma volume or renal arteriolar constriction. Its treatment is disappointing and in spite of new technics, gives only transitory improvements."}
{"id": "PMID:231841", "title": "[Review on the properties of glial cells of the central nervous system (author's transl)].", "content": "During the past 15 years, increasing studies have been devoted to glial cells, i.e. oligodendrocytes, astrocytes and microglial cells of the central nervous system. Although most of their functions remain mysterious, the concept of intracellular interactions between neurons and neuroglia becomes more and more substantiated. This review describes some aspects of phylogeny of glia, recent technical approaches to the study of these cells, their major morphological and biochemical characteristics, their maturation as well as their pathology.", "contents": "[Review on the properties of glial cells of the central nervous system (author's transl)]. During the past 15 years, increasing studies have been devoted to glial cells, i.e. oligodendrocytes, astrocytes and microglial cells of the central nervous system. Although most of their functions remain mysterious, the concept of intracellular interactions between neurons and neuroglia becomes more and more substantiated. This review describes some aspects of phylogeny of glia, recent technical approaches to the study of these cells, their major morphological and biochemical characteristics, their maturation as well as their pathology."}
{"id": "PMID:231857", "title": "Silica and silicates in femoral lymph nodes of barefooted people in Ethiopia with special reference to elephantiasis of the lower legs.", "content": "Electron microscopy of femoral lymph nodes of barefooted Ethiopians show the presence of numerous particles of colloid-size and electron-density in the lysosomes of the macrophages in the gland. On diffraction analysis, the particles are found to be amorphous. Elemental microanalysis of the X-ray spectrum indicate the predominance of Si, Al and Fe. In elephantiasics some particles contain silicon alone, presumably silica. The distribution of the Al/Si ratios of the particles in subjects with elephantiasis of the lower legs show a difference from that of non-elephantiasics which is statistically \"highly significant\" at p less than 0.001. The importance of this as a possible aetiological factor in the disease is discussed. The hypothesis that the disease is discussed. The hypothesis that the disease is a silicosis of the peripheral lymphatics of the lower limbs is supported by the present study.", "contents": "Silica and silicates in femoral lymph nodes of barefooted people in Ethiopia with special reference to elephantiasis of the lower legs. Electron microscopy of femoral lymph nodes of barefooted Ethiopians show the presence of numerous particles of colloid-size and electron-density in the lysosomes of the macrophages in the gland. On diffraction analysis, the particles are found to be amorphous. Elemental microanalysis of the X-ray spectrum indicate the predominance of Si, Al and Fe. In elephantiasics some particles contain silicon alone, presumably silica. The distribution of the Al/Si ratios of the particles in subjects with elephantiasis of the lower legs show a difference from that of non-elephantiasics which is statistically \"highly significant\" at p less than 0.001. The importance of this as a possible aetiological factor in the disease is discussed. The hypothesis that the disease is discussed. The hypothesis that the disease is a silicosis of the peripheral lymphatics of the lower limbs is supported by the present study."}
{"id": "PMID:231858", "title": "Inhibition of lactate dehydrogenase activity from Dirofilaria immitis by suramin.", "content": "Lactate dehydrogenase from adult D. immitis was partially purified and characterized. The molecular weight of the enzyme was determined to be 130 000. The specific activity of the lactate dehydrogenase was 4.1 U/mg in the direction of NADH-oxidation and 0.38 U/mg protein in the direction of NAD-reduction. The Michaelis constants were determined to be 0.028 mM and 0.9 mM for NADH and NAD, respectively. Suramin was found to be a potent inhibitor of the lactate dehydrogenase activity. The inhibition constant was calculated to be 0.006 mM. The type of inhibition by suramin was competitive with respect to the cofactors. The Km-values for pyruvate and lactate were determined to be 0.3 mM and 11mM, respectively.", "contents": "Inhibition of lactate dehydrogenase activity from Dirofilaria immitis by suramin. Lactate dehydrogenase from adult D. immitis was partially purified and characterized. The molecular weight of the enzyme was determined to be 130 000. The specific activity of the lactate dehydrogenase was 4.1 U/mg in the direction of NADH-oxidation and 0.38 U/mg protein in the direction of NAD-reduction. The Michaelis constants were determined to be 0.028 mM and 0.9 mM for NADH and NAD, respectively. Suramin was found to be a potent inhibitor of the lactate dehydrogenase activity. The inhibition constant was calculated to be 0.006 mM. The type of inhibition by suramin was competitive with respect to the cofactors. The Km-values for pyruvate and lactate were determined to be 0.3 mM and 11mM, respectively."}
{"id": "PMID:231859", "title": "Study of cell surface antigens induced by herpes simplex virus. Note II. Some properties of the antigens.", "content": "Surface antigens induced by herpes simplex virus infection in HeLa cells remain unaltered after treatment of the cells with 2% formalin for 10 min or with 0.08% trypsin for 15 min at 37 degrees C. A longer trypsin treatment (for 1 hour) will cause gradual alterations in the virus-induced antigens. Hence, these antigens are proteins deeply implanted within the cellular membrane. Their mobility--optimal at 37 degrees C--allows aggregation of the antigens in the form of caps or patches by polyvalent ligands such as IgG.", "contents": "Study of cell surface antigens induced by herpes simplex virus. Note II. Some properties of the antigens. Surface antigens induced by herpes simplex virus infection in HeLa cells remain unaltered after treatment of the cells with 2% formalin for 10 min or with 0.08% trypsin for 15 min at 37 degrees C. A longer trypsin treatment (for 1 hour) will cause gradual alterations in the virus-induced antigens. Hence, these antigens are proteins deeply implanted within the cellular membrane. Their mobility--optimal at 37 degrees C--allows aggregation of the antigens in the form of caps or patches by polyvalent ligands such as IgG."}
{"id": "PMID:231860", "title": "Transplacental cancerization by Rous sarcoma virus.", "content": "Experimental data obtained in the mouse are presented, pointing to the possibility of transplacental transmission of the genetic information contained in the genome of Rous sarcoma virus(RSV), by either intact RSV virions or nucleic acids extracted from infectant suspensions of tumors induced by the Carr(Ziber) on Bryan RSV strains.", "contents": "Transplacental cancerization by Rous sarcoma virus. Experimental data obtained in the mouse are presented, pointing to the possibility of transplacental transmission of the genetic information contained in the genome of Rous sarcoma virus(RSV), by either intact RSV virions or nucleic acids extracted from infectant suspensions of tumors induced by the Carr(Ziber) on Bryan RSV strains."}
{"id": "PMID:231861", "title": "Enterovirus diseases with neurological determinations in adults. Clinical and virological study.", "content": "Enteroviruses--4 polio, 30 Coxsackie and 20 echovirus strains--were isolated from 54 patients with neurologic disease. In 29 cases (53.7%) viruses were isolated from the CSF, blood clot and nerve tissue homogenates. The correlation of the complex clinical data and the localisation of the lesions in the CNS demonstrate the involvement of cranial nerves, of the long bulbar motor pyramidal and extra-pyramidal tracts, of the reticular formation, a.o. These aspects are in accordance with the localisation of the lesions especially in the brain stem and in the hypothalamus, in most of our patients. The extent and complexity of the lesions suggest a predominatly vascular dissemination.", "contents": "Enterovirus diseases with neurological determinations in adults. Clinical and virological study. Enteroviruses--4 polio, 30 Coxsackie and 20 echovirus strains--were isolated from 54 patients with neurologic disease. In 29 cases (53.7%) viruses were isolated from the CSF, blood clot and nerve tissue homogenates. The correlation of the complex clinical data and the localisation of the lesions in the CNS demonstrate the involvement of cranial nerves, of the long bulbar motor pyramidal and extra-pyramidal tracts, of the reticular formation, a.o. These aspects are in accordance with the localisation of the lesions especially in the brain stem and in the hypothalamus, in most of our patients. The extent and complexity of the lesions suggest a predominatly vascular dissemination."}
{"id": "PMID:231865", "title": "Regulative influence of o-aminobenzoic acid on the biosynthesis of nourseothricin in cultures of Streptomyces noursei JA 3890b. IV. Bistability of metabolism and the mechanism of action of aminobenzoic acids.", "content": "Using the semi-continuous cultivation technique we could establish that specifically in Streptomyces noursei JA 3890b during growth on a medium supplied with D,L-alanine, NH4+, and maize starch there are two different phenotypes of the organism and stationary states of metabolism, respectively. The expression of either the metabolic state I with an enhanced capacity to oxidative deamination of alanine via the NAD+-dependent alanaine dehydrogenase or the metabolic state 2 which may be characterized by the preferred use of ammonium ions via the NADP+-dependent glutamate dehydrogenase was shown to depend strongly on the conditions of inoculum cultivation. When the amino acid permeases were derepressed by cultivating the inoculum cells on amino acid media, probably due to the defective mechanism of negative feedback control of amino acid influx in this strain an abnormously high uptake of alanine was observed that, consequently, was correlated to the enhanced oxidation of this amino acid as well as to the intensive production of ammonia within the cell. This overproduction of cellular NH4+ seems to bring about the subsequent repression of biosynthetic glutamate dehydrogenase and so on the accumulation of ammonia autocatalytically may rise up (metabolic state I). On the other hand, if the influx of alanine was kept low and the NADH oxidation was less efficient, respectively, or when there was high cellular activity of glutamate dehydrogenase the level of ammonia never did exceed the respressory limit and, accordingly, the expression of the metabolic state 2 was observed. Switching-over of metabolic flux from the state 2 towards the state 1 can be brought about either by increasing the level of nitrogen sources in the medium or by adding buffers pH greater than 7.5. In contrast, decrease of cellular level of NH4+ was shown to induce the transition of metabolic state 1 into the state 2. This can be achieved not only by limitation of nitrogen source but also by adding different aminobenzoic acids and, alternatively, effectors of membrane function (short-chain alcohols), inhibitors of cytochrome oxidases (sodium azide, potassium cyanide), heavy metal (Fe++)-chelating agents (catechol, 2,5'-dipyridyl, o-phenanthroline), beta-alanine, and buffers pH less than 7. This suggests that these effectors are capable of preventing the abnormously high influx of amino acids as well as its wasteful catabolism within the cell of S. noursei JA 3890b. Therefore, it seems likely that by this way the aminobenzoic acids and similar effectors can diminish the catabolite repression or inhibition of secondary metabolism by cellular excess of some nitrogen compounds in good agreement with its well-known stimulatory action on the biosynthesis of the antibiotic nourseothricin in this strain.", "contents": "Regulative influence of o-aminobenzoic acid on the biosynthesis of nourseothricin in cultures of Streptomyces noursei JA 3890b. IV. Bistability of metabolism and the mechanism of action of aminobenzoic acids. Using the semi-continuous cultivation technique we could establish that specifically in Streptomyces noursei JA 3890b during growth on a medium supplied with D,L-alanine, NH4+, and maize starch there are two different phenotypes of the organism and stationary states of metabolism, respectively. The expression of either the metabolic state I with an enhanced capacity to oxidative deamination of alanine via the NAD+-dependent alanaine dehydrogenase or the metabolic state 2 which may be characterized by the preferred use of ammonium ions via the NADP+-dependent glutamate dehydrogenase was shown to depend strongly on the conditions of inoculum cultivation. When the amino acid permeases were derepressed by cultivating the inoculum cells on amino acid media, probably due to the defective mechanism of negative feedback control of amino acid influx in this strain an abnormously high uptake of alanine was observed that, consequently, was correlated to the enhanced oxidation of this amino acid as well as to the intensive production of ammonia within the cell. This overproduction of cellular NH4+ seems to bring about the subsequent repression of biosynthetic glutamate dehydrogenase and so on the accumulation of ammonia autocatalytically may rise up (metabolic state I). On the other hand, if the influx of alanine was kept low and the NADH oxidation was less efficient, respectively, or when there was high cellular activity of glutamate dehydrogenase the level of ammonia never did exceed the respressory limit and, accordingly, the expression of the metabolic state 2 was observed. Switching-over of metabolic flux from the state 2 towards the state 1 can be brought about either by increasing the level of nitrogen sources in the medium or by adding buffers pH greater than 7.5. In contrast, decrease of cellular level of NH4+ was shown to induce the transition of metabolic state 1 into the state 2. This can be achieved not only by limitation of nitrogen source but also by adding different aminobenzoic acids and, alternatively, effectors of membrane function (short-chain alcohols), inhibitors of cytochrome oxidases (sodium azide, potassium cyanide), heavy metal (Fe++)-chelating agents (catechol, 2,5'-dipyridyl, o-phenanthroline), beta-alanine, and buffers pH less than 7. This suggests that these effectors are capable of preventing the abnormously high influx of amino acids as well as its wasteful catabolism within the cell of S. noursei JA 3890b. Therefore, it seems likely that by this way the aminobenzoic acids and similar effectors can diminish the catabolite repression or inhibition of secondary metabolism by cellular excess of some nitrogen compounds in good agreement with its well-known stimulatory action on the biosynthesis of the antibiotic nourseothricin in this strain."}
{"id": "PMID:231866", "title": "Regulation of Neurospora crassa nucleosidases by some environmental factors.", "content": "Enzymic cleavage of N-glycosidic bonds of AMP, GMP, and inosine by the cell-free extracts of Neurospora crassa has been studied. The enzymic activities with these substrates appear to be discrete from one another. The levels of these enzymes in the cell vary with age, and are dependent upon the inoculum size, aeration rate, and phosphate level in the medium. Glucose (or ribose) controls the phosphate-mediated repression of all the three nucleosidases of this fungus.", "contents": "Regulation of Neurospora crassa nucleosidases by some environmental factors. Enzymic cleavage of N-glycosidic bonds of AMP, GMP, and inosine by the cell-free extracts of Neurospora crassa has been studied. The enzymic activities with these substrates appear to be discrete from one another. The levels of these enzymes in the cell vary with age, and are dependent upon the inoculum size, aeration rate, and phosphate level in the medium. Glucose (or ribose) controls the phosphate-mediated repression of all the three nucleosidases of this fungus."}
{"id": "PMID:231868", "title": "[Eye and lymph drainage].", "content": "Up to now lymphatics in the eye could not be pointed out. An ocular lymph drainage is denied. F\u00f6ldi succeeded in producing experimentally the syndrome of \"lymphostatic encephalopathy and ophthalmopathy\" by operative blockade of the cervical lymphatics in animals. In the first part of the present paper a historical view considering the subject \"Eye and lymphatic system\" is given. In the second part it is entered into the particulars of own experimental studies. As to our own investigations, rabbits have been injected 99mTc-sulfur-colloid, 99mTc-microcolloid, 99mTc-Albumin and 198Au-colloid into the retrobulbar space, anterior chamber, vitreous body and subconjuctival space of one eye. Measurements of the activity's distribution have been made in vivo with an Anger type camera (pho-Gamma-IV Hp, Searle Nuclear Chicago) and in vitro after section with a sodium iodine crystal well counter (Clinimat-200, Picker). In some animals the investigation has been combined with a bilateral dissection of the cervical lymph nodes. After injection in the retrobulbar space a significant concentration of the activity could be observed for the most part in the equilateral Lymphonodulus cervicalis profundus. By the cervical lymph blockade the removal of lymphoctopic substances from the retrobulbar space was largely inhibited. After injection in the anterior chamber a significant concentration could be observed for the most part in the equilateral Lymphonodulus cervicalis superficialis. After intravitreal injection a drainage to the bilateral deep cervical lymph nodes could be observed. After injection into the subconjunctival space a significant accumulation of activity could be registered in the equilateral Lymphonoduli mandibulares and cervicales superficiales. The data substantiate a segmental lymph drainage from the eye: vitreous body and retrobulbar space for the most part into the Lymphonoduli cervicales profundi, anterior chamber and subconjunctival space for the most part into the Lymphonoduli cervicales superficiales been studied. In albino-rabbits indiaink has been injected into the vitreous body and afterwards its drainage has been controlled histologically (frozen sections). In some animals the investigation has been combined with a bilateral dissection of the cervical lymph nodes. The lymph node dissection causes a massive deceleration of the India-ink's outflow; the perivascular connective tissue shows a clear edematous relaxation. The histological evidence suggests that 1. the vitreous body 2. the interstice between the glia cells of the papilla 3. the pial tissue between the neurone bundles of the optic nerve 4. the perivascular space around the central vessels of the retina 5. the subarachnoid sheath of the optic nerve may be interpreted as prelymphatic pathway.", "contents": "[Eye and lymph drainage]. Up to now lymphatics in the eye could not be pointed out. An ocular lymph drainage is denied. F\u00f6ldi succeeded in producing experimentally the syndrome of \"lymphostatic encephalopathy and ophthalmopathy\" by operative blockade of the cervical lymphatics in animals. In the first part of the present paper a historical view considering the subject \"Eye and lymphatic system\" is given. In the second part it is entered into the particulars of own experimental studies. As to our own investigations, rabbits have been injected 99mTc-sulfur-colloid, 99mTc-microcolloid, 99mTc-Albumin and 198Au-colloid into the retrobulbar space, anterior chamber, vitreous body and subconjuctival space of one eye. Measurements of the activity's distribution have been made in vivo with an Anger type camera (pho-Gamma-IV Hp, Searle Nuclear Chicago) and in vitro after section with a sodium iodine crystal well counter (Clinimat-200, Picker). In some animals the investigation has been combined with a bilateral dissection of the cervical lymph nodes. After injection in the retrobulbar space a significant concentration of the activity could be observed for the most part in the equilateral Lymphonodulus cervicalis profundus. By the cervical lymph blockade the removal of lymphoctopic substances from the retrobulbar space was largely inhibited. After injection in the anterior chamber a significant concentration could be observed for the most part in the equilateral Lymphonodulus cervicalis superficialis. After intravitreal injection a drainage to the bilateral deep cervical lymph nodes could be observed. After injection into the subconjunctival space a significant accumulation of activity could be registered in the equilateral Lymphonoduli mandibulares and cervicales superficiales. The data substantiate a segmental lymph drainage from the eye: vitreous body and retrobulbar space for the most part into the Lymphonoduli cervicales profundi, anterior chamber and subconjunctival space for the most part into the Lymphonoduli cervicales superficiales been studied. In albino-rabbits indiaink has been injected into the vitreous body and afterwards its drainage has been controlled histologically (frozen sections). In some animals the investigation has been combined with a bilateral dissection of the cervical lymph nodes. The lymph node dissection causes a massive deceleration of the India-ink's outflow; the perivascular connective tissue shows a clear edematous relaxation. The histological evidence suggests that 1. the vitreous body 2. the interstice between the glia cells of the papilla 3. the pial tissue between the neurone bundles of the optic nerve 4. the perivascular space around the central vessels of the retina 5. the subarachnoid sheath of the optic nerve may be interpreted as prelymphatic pathway."}
{"id": "PMID:231864", "title": "The shark rectal gland: a model for the active transport of chloride.", "content": "The rectal gland of the spiny dogfish, Squalus acanthias, provides an easily studied model of active chloride transport powered indirectly by Na-K-ATPase. Co-transport of sodium with chloride can be demonstrated in membrane vesicles isolated from basolateral membranes of the gland. Chloride secretion is under the hormonal control of vasoactive intestinal peptide, and possibly other agents, via adenyl cyclase and cyclic AMP. A similar mechanism is probably responsible for the active transport of chloride across other biological membranes.", "contents": "The shark rectal gland: a model for the active transport of chloride. The rectal gland of the spiny dogfish, Squalus acanthias, provides an easily studied model of active chloride transport powered indirectly by Na-K-ATPase. Co-transport of sodium with chloride can be demonstrated in membrane vesicles isolated from basolateral membranes of the gland. Chloride secretion is under the hormonal control of vasoactive intestinal peptide, and possibly other agents, via adenyl cyclase and cyclic AMP. A similar mechanism is probably responsible for the active transport of chloride across other biological membranes."}
{"id": "PMID:231878", "title": "Insulin response to an oral glucose load in relation to Lp(a)/pre-beta 1-lipoprotein levels in non-diabetic patients with peripheral vascular disease and in controls.", "content": "An oral glucose tolerance test (OGTT) was performed in 21 patients with previously known or recently detected peripheral vascular disease as well as in 16 age-matched controls. The angiographic results and the results in a physiological investigation were used to classify patients with high and low stenosis and normal controls, respectively. No significant differences in mean levels of insulin and blood glucose were found between patients with high and low stenosis, respectively, or between normal controls and (a) the whole group of patients with high stenosis, (b) only those with high stenosis who had not undergone arterial surgery. However, individuals with high amounts of Lp(a) lipoprotein were found to have significantly lower insulin mean levels during the OGTT and an even lower mean fasting level as compared to individuals without detectable Lp(a) lipoprotein. In the group of individuals with high amounts of Lp(a) lipoprotein, the glucose mean levels were also significantly lower, during a part of the OGTT. These findings are in agreement with previous results and suggest that inherited metabolic differences exist between individuals with high and zero or low levels of Lp(a) lipoprotein.", "contents": "Insulin response to an oral glucose load in relation to Lp(a)/pre-beta 1-lipoprotein levels in non-diabetic patients with peripheral vascular disease and in controls. An oral glucose tolerance test (OGTT) was performed in 21 patients with previously known or recently detected peripheral vascular disease as well as in 16 age-matched controls. The angiographic results and the results in a physiological investigation were used to classify patients with high and low stenosis and normal controls, respectively. No significant differences in mean levels of insulin and blood glucose were found between patients with high and low stenosis, respectively, or between normal controls and (a) the whole group of patients with high stenosis, (b) only those with high stenosis who had not undergone arterial surgery. However, individuals with high amounts of Lp(a) lipoprotein were found to have significantly lower insulin mean levels during the OGTT and an even lower mean fasting level as compared to individuals without detectable Lp(a) lipoprotein. In the group of individuals with high amounts of Lp(a) lipoprotein, the glucose mean levels were also significantly lower, during a part of the OGTT. These findings are in agreement with previous results and suggest that inherited metabolic differences exist between individuals with high and zero or low levels of Lp(a) lipoprotein."}
{"id": "PMID:231880", "title": "Histochemical characteristics of diphosphate nucleoside consumption in cat and rat nervous system.", "content": "Consumption of diphosphate nucleosides is investigated by histochemical methods in rat and cat nervous system. Results show NDP-ase is effectively in histological sections from animals previously perfused with glutaraldehyde or formaldehyde. Histochemical reaction is increased in presence of Ca++, Mg++, Mn++ or imidazole and inhibited by L-DOPA and Noradrenaline in incubation medium. A comparative study of TPP-ase and NDP-ase activities to dilucidate the identity of both enzymes is described.", "contents": "Histochemical characteristics of diphosphate nucleoside consumption in cat and rat nervous system. Consumption of diphosphate nucleosides is investigated by histochemical methods in rat and cat nervous system. Results show NDP-ase is effectively in histological sections from animals previously perfused with glutaraldehyde or formaldehyde. Histochemical reaction is increased in presence of Ca++, Mg++, Mn++ or imidazole and inhibited by L-DOPA and Noradrenaline in incubation medium. A comparative study of TPP-ase and NDP-ase activities to dilucidate the identity of both enzymes is described."}
{"id": "PMID:231881", "title": "[Electron-microscopic investigations on the localisation of the thiamine pyrophosphatase in the hippocampus of the Wistar rat (author's transl)].", "content": "This report describes the ultratopochemical localization of the thiamine pyrophosphatase in the pyramidal cells of the CA3 region of Wistar rat hippocampus. Attention was focussed on the occurrence of the enzyme out of the Golgi field. Thiamine pyrophosphatase was demonstrated in dendrites and - to a lesser extent - in axons. TTPase containing synapses were rather seldom and belonged to the axo-dendritic type. A hypothetic model concerning the transport and the distribution of the enzyme within the cell is presented.", "contents": "[Electron-microscopic investigations on the localisation of the thiamine pyrophosphatase in the hippocampus of the Wistar rat (author's transl)]. This report describes the ultratopochemical localization of the thiamine pyrophosphatase in the pyramidal cells of the CA3 region of Wistar rat hippocampus. Attention was focussed on the occurrence of the enzyme out of the Golgi field. Thiamine pyrophosphatase was demonstrated in dendrites and - to a lesser extent - in axons. TTPase containing synapses were rather seldom and belonged to the axo-dendritic type. A hypothetic model concerning the transport and the distribution of the enzyme within the cell is presented."}
{"id": "PMID:231882", "title": "Mucosaccharide histochemistry and histoenzymorphologic observations on the epidermis of Ariosoma balearicum de la Roche (Anguilliformes, Pisces).", "content": "The epidermis of Ariosoma balearicum consists of three layers - the basal layer, the middle layer and the outer layer. In between the basal cells are found clusters of small lymphocytes which show a moderat acid phosphatase activity. The middle layer and the outer layer are composed of three types of cells - the polygonal cells, the mucous cells and the club cells. The mucosubstances within the mucous cells exhibit the properties of neuraminic acid containing mucosaccharides with vicinal hydroxyl, sulfate esters and carboxyl groupings. The superficial cells of the outermost layer are capable of secreting sulphated and carboxylated mucosubstances to form an extracellular mucous coating which in fish epidermis seems to be necessary for the accumulation of electrolytes. The club cells are generally provided with one nucleus or double nuclei which appear displaced from the center and constitute the main histological component of the middle layer. The contents of these cells, in addition to a strong protein uptake visualized by the positive reactions exhibited in the coupled tetrazonium and mercuric bromophenol blue preparations, gave positive response to neutral mucosubstances which appear to be a glycoprotein involved in the slime secretions. Alkaline phosphatase and TPP-hydrolysing enzyme which could be detectable in the basal layer and the basement membrane were correlated with the probable role that they could play in the transportation of various chemicals and nutriments through the cell membranes.", "contents": "Mucosaccharide histochemistry and histoenzymorphologic observations on the epidermis of Ariosoma balearicum de la Roche (Anguilliformes, Pisces). The epidermis of Ariosoma balearicum consists of three layers - the basal layer, the middle layer and the outer layer. In between the basal cells are found clusters of small lymphocytes which show a moderat acid phosphatase activity. The middle layer and the outer layer are composed of three types of cells - the polygonal cells, the mucous cells and the club cells. The mucosubstances within the mucous cells exhibit the properties of neuraminic acid containing mucosaccharides with vicinal hydroxyl, sulfate esters and carboxyl groupings. The superficial cells of the outermost layer are capable of secreting sulphated and carboxylated mucosubstances to form an extracellular mucous coating which in fish epidermis seems to be necessary for the accumulation of electrolytes. The club cells are generally provided with one nucleus or double nuclei which appear displaced from the center and constitute the main histological component of the middle layer. The contents of these cells, in addition to a strong protein uptake visualized by the positive reactions exhibited in the coupled tetrazonium and mercuric bromophenol blue preparations, gave positive response to neutral mucosubstances which appear to be a glycoprotein involved in the slime secretions. Alkaline phosphatase and TPP-hydrolysing enzyme which could be detectable in the basal layer and the basement membrane were correlated with the probable role that they could play in the transportation of various chemicals and nutriments through the cell membranes."}
{"id": "PMID:231883", "title": "[The mechanism of the tetrazolium reduction and the effect of phenazinmethosulfate (author's transl)].", "content": "Modern results of the literature form the basis for the presentation of a scheme which shows the reduction of tetrazolium salts and the action of phenazine methosulfate under histochemical conditions. The reduction of tetrazolium salts passes the radical state and it hapens principally on the niveau of the flavin proteins and the ubiquinone. The importance of the superoxide radical for the reduction of tetrazolium salts under aerobic conditions is emphasized.", "contents": "[The mechanism of the tetrazolium reduction and the effect of phenazinmethosulfate (author's transl)]. Modern results of the literature form the basis for the presentation of a scheme which shows the reduction of tetrazolium salts and the action of phenazine methosulfate under histochemical conditions. The reduction of tetrazolium salts passes the radical state and it hapens principally on the niveau of the flavin proteins and the ubiquinone. The importance of the superoxide radical for the reduction of tetrazolium salts under aerobic conditions is emphasized."}
{"id": "PMID:231884", "title": "Histochemical and ultrastructural study of adult human tendon.", "content": "The authors have studied the enzymhistochemical and ultrastructural pictures of tenocytes of adult human tendons. High succinate dehydrogenase, cytochrome oxidase, TPN-diaphorase, lactate dehydrogenase and glucose-6-phosphate dehydrogenase activity were found, as indicated both oxidativ, anaerobic and pentose-phosphate shung activity. Phosphorylase and glutamate dehydrogenase activity was medial, lipase and alcaline phosphatase activity was slight. In tenocytes well developed rough endoplasmic reticulum and GOLGI apparatus, large amount of free ribosomes were found.", "contents": "Histochemical and ultrastructural study of adult human tendon. The authors have studied the enzymhistochemical and ultrastructural pictures of tenocytes of adult human tendons. High succinate dehydrogenase, cytochrome oxidase, TPN-diaphorase, lactate dehydrogenase and glucose-6-phosphate dehydrogenase activity were found, as indicated both oxidativ, anaerobic and pentose-phosphate shung activity. Phosphorylase and glutamate dehydrogenase activity was medial, lipase and alcaline phosphatase activity was slight. In tenocytes well developed rough endoplasmic reticulum and GOLGI apparatus, large amount of free ribosomes were found."}
{"id": "PMID:231879", "title": "Endobronchial granular cell tumor. Cytology of a new case and review of the literature.", "content": "We report the 45th case of endobronchial granular cell tumor in the literature and describe in detail the cytologic findings in bronchial brushings and post-brush washings. Our findings differ from those of the only other cytologic report of such a lesion. We review the literature and summarize the clinical and pathologic findings of endobronchial granular cell tumors. Cytologically the differential diagnosis is between granular cells, respiratory epithelial cells and macrophages. We feel that our criteria make the distinction between them easy. However, most importantly, one must suspect the lesion; otherwise, these \"benign cells\" will be passed over by the screening cytotechnologist.", "contents": "Endobronchial granular cell tumor. Cytology of a new case and review of the literature. We report the 45th case of endobronchial granular cell tumor in the literature and describe in detail the cytologic findings in bronchial brushings and post-brush washings. Our findings differ from those of the only other cytologic report of such a lesion. We review the literature and summarize the clinical and pathologic findings of endobronchial granular cell tumors. Cytologically the differential diagnosis is between granular cells, respiratory epithelial cells and macrophages. We feel that our criteria make the distinction between them easy. However, most importantly, one must suspect the lesion; otherwise, these \"benign cells\" will be passed over by the screening cytotechnologist."}
{"id": "PMID:231885", "title": "Regional ketamine-induced depression of neuromuscular transmission in man.", "content": "The intravenous injection of ketamine in the human arm with isolated circulation, using the same technique as for intravenous regional anesthesia, produces a dose-related depression of neuromuscular transmission, as evidenced by the evoked response to supramaximal stimulation of the ulnar nerve with a nerve stimulator. The dose range of ketamine was 200, 25, 10, 5, 1, 0.5 and 0.25 mg, in 20 ml of 5% dextrose in water. The exact mechanism of this effect is discussed. This depression may have clinical significance under certain circumstances.", "contents": "Regional ketamine-induced depression of neuromuscular transmission in man. The intravenous injection of ketamine in the human arm with isolated circulation, using the same technique as for intravenous regional anesthesia, produces a dose-related depression of neuromuscular transmission, as evidenced by the evoked response to supramaximal stimulation of the ulnar nerve with a nerve stimulator. The dose range of ketamine was 200, 25, 10, 5, 1, 0.5 and 0.25 mg, in 20 ml of 5% dextrose in water. The exact mechanism of this effect is discussed. This depression may have clinical significance under certain circumstances."}
{"id": "PMID:231886", "title": "Nuclear inclusions in the human adenohypophysis. A fine-structural study of nontumorous and adenomatous pituitaries.", "content": "Electron microscopy revealed the presence of nonviral nuclear inclusions in human nontumorous as well as adenomatous adenohypophysiocytes, regardless of cell type. Based on ultrastructural appearances, the inclusions have been classified as simple bodies, complex bodies and filamentous aggregates. Many transitional forms were noted between the simple and complex bodies, however, no relationship between the nuclear bodies and filamentous aggregates was found. It can be concluded that the three types of inclusions are normal nuclear constituents. Since no accumulation of these structures was observed in cells associated with enhanced secretion it appears that they are not related to hormonal hyperactivity in the human adenohypophysis.", "contents": "Nuclear inclusions in the human adenohypophysis. A fine-structural study of nontumorous and adenomatous pituitaries. Electron microscopy revealed the presence of nonviral nuclear inclusions in human nontumorous as well as adenomatous adenohypophysiocytes, regardless of cell type. Based on ultrastructural appearances, the inclusions have been classified as simple bodies, complex bodies and filamentous aggregates. Many transitional forms were noted between the simple and complex bodies, however, no relationship between the nuclear bodies and filamentous aggregates was found. It can be concluded that the three types of inclusions are normal nuclear constituents. Since no accumulation of these structures was observed in cells associated with enhanced secretion it appears that they are not related to hormonal hyperactivity in the human adenohypophysis."}
{"id": "PMID:231889", "title": "T and B lymphocyte subpopulations and leukocyte terminal deoxynucleotidyl-transferase in energy-protein undernutrition.", "content": "Children with energy-protein undernutrition showed a reduction in the number of circulating T lymphocytes identified on the basis of their ability to form rosettes with sheep red blood cells. T cells with a receptor for IgM (Tmu) were decreased whereas T cells with a receptor for IgG (T gamma) were increased. Surface immunoglobulin bearing B cells were comparable in well nourished and malnourished subjects but the proportion of B alpha was increased in the latter. \"Null\" cells without the conventional markers of T or B cells were proportionately increased. Leukocyte terminal deoxynucleotidyl-transferase activity was elevated in the majority of undernourished children and correlated with the proportion of \"null\" cells. The significance of these observations is discussed and it is suggested that \"null\" cells represent immature undifferentiated T lymphocytes.", "contents": "T and B lymphocyte subpopulations and leukocyte terminal deoxynucleotidyl-transferase in energy-protein undernutrition. Children with energy-protein undernutrition showed a reduction in the number of circulating T lymphocytes identified on the basis of their ability to form rosettes with sheep red blood cells. T cells with a receptor for IgM (Tmu) were decreased whereas T cells with a receptor for IgG (T gamma) were increased. Surface immunoglobulin bearing B cells were comparable in well nourished and malnourished subjects but the proportion of B alpha was increased in the latter. \"Null\" cells without the conventional markers of T or B cells were proportionately increased. Leukocyte terminal deoxynucleotidyl-transferase activity was elevated in the majority of undernourished children and correlated with the proportion of \"null\" cells. The significance of these observations is discussed and it is suggested that \"null\" cells represent immature undifferentiated T lymphocytes."}
{"id": "PMID:231891", "title": "Influence of lithium on cyclic AMP accumulation in isolated rat fat cells.", "content": "Lithium inhibits in vitro as well as in vivo several hormone-stimulated adenylate cyclases. The aim of this study was to investigate the mechanism by which lithium inhibits adenylate cyclase in vitro. It was found that lithium inhibited both the norepinephrine- and the glucagon-induced cAMP accumulation in rat fat cells at lithium concentrations above 10 mM. The basal cAMP content was unaffected even at 40 mM of lithium. The inhibitory action was time-dependent and reversible, indicating an intracellular site of action. Lithium inhibited both norepinephrine- and glucagon-stimulated cAMP accumulation in a mainly non-competitive way, but the inhibitory effect decreased with increasing hormone concentrations. In accordance, lithium and propranolol had a supraadditive effect on norepinephrine-induced cAMP accumulation. It is suggested that lithium affects both the hormone-receptor binding as well as the transfer of the hormonal stimulus by an intracellular site of action.", "contents": "Influence of lithium on cyclic AMP accumulation in isolated rat fat cells. Lithium inhibits in vitro as well as in vivo several hormone-stimulated adenylate cyclases. The aim of this study was to investigate the mechanism by which lithium inhibits adenylate cyclase in vitro. It was found that lithium inhibited both the norepinephrine- and the glucagon-induced cAMP accumulation in rat fat cells at lithium concentrations above 10 mM. The basal cAMP content was unaffected even at 40 mM of lithium. The inhibitory action was time-dependent and reversible, indicating an intracellular site of action. Lithium inhibited both norepinephrine- and glucagon-stimulated cAMP accumulation in a mainly non-competitive way, but the inhibitory effect decreased with increasing hormone concentrations. In accordance, lithium and propranolol had a supraadditive effect on norepinephrine-induced cAMP accumulation. It is suggested that lithium affects both the hormone-receptor binding as well as the transfer of the hormonal stimulus by an intracellular site of action."}
{"id": "PMID:231892", "title": "On the mechanism of relaxation of tracheal muscle by theophylline and other cyclic nucleotide phosphodiesterase inhibitors.", "content": "The mechamism of action of theophylline was studied by investigating the relationship between relaxant effect and inhibition of cyclic nucleotide phosphodiesterase (PDE) and by studying interactions with adenosine actions. Guinea pig tracheal smooth muscle cyclic AMP PDE had two apparent KmS': 0.4 and 70 microM for cyclic AMP. Theophylline and papaverine competetively inhibited the low Km form. Hydrolysis of 2.0 microM cyclic AMP and cyclic GMP was inhibited by several drugs. Some agents (e.g. ZK 62 711, ICI 63,197, Ro 20--1724, dipyridamol) were considerably more potent as inhibitors of cyclic AMP than of cyclic GMP hydrolysis, while other agents (M & B 22.948 and dilazep) selectively inhibited cyclic GMP breakdown, and some (theophylline, papaverine, IBMX and SQ 20,006) showed little selectivity. There was a weak but significant correlation between inhibition of cyclic AMP phosphodiesterase and relaxation of tracheal smooth muscle in vitro. There was also a correlation between the ratio of IC25 cyclic AMP/IC25 cyclic GMP and the smooth muscle relaxation, indicating that inhibition of cyclic AMP rather than cyclic GMP hydrolysis determined relaxation. However, there was a marked tachyphylaxis to the relaxant effect of the cyclic AMP selective PDE-inhibitors, while the nonselective methylxanthines did not show tachyphylaxis. The effect of theophylline was antagonized by low concentrations of adenosine, which by itself caused a weak tracheal contraction. The effect of PDI-inhibitors can be partly explained by decreased cyclic AMP breakdown but other mechanisms, such as antagonism of endogenous adenosine, may contribute to the observed relaxant action.", "contents": "On the mechanism of relaxation of tracheal muscle by theophylline and other cyclic nucleotide phosphodiesterase inhibitors. The mechamism of action of theophylline was studied by investigating the relationship between relaxant effect and inhibition of cyclic nucleotide phosphodiesterase (PDE) and by studying interactions with adenosine actions. Guinea pig tracheal smooth muscle cyclic AMP PDE had two apparent KmS': 0.4 and 70 microM for cyclic AMP. Theophylline and papaverine competetively inhibited the low Km form. Hydrolysis of 2.0 microM cyclic AMP and cyclic GMP was inhibited by several drugs. Some agents (e.g. ZK 62 711, ICI 63,197, Ro 20--1724, dipyridamol) were considerably more potent as inhibitors of cyclic AMP than of cyclic GMP hydrolysis, while other agents (M & B 22.948 and dilazep) selectively inhibited cyclic GMP breakdown, and some (theophylline, papaverine, IBMX and SQ 20,006) showed little selectivity. There was a weak but significant correlation between inhibition of cyclic AMP phosphodiesterase and relaxation of tracheal smooth muscle in vitro. There was also a correlation between the ratio of IC25 cyclic AMP/IC25 cyclic GMP and the smooth muscle relaxation, indicating that inhibition of cyclic AMP rather than cyclic GMP hydrolysis determined relaxation. However, there was a marked tachyphylaxis to the relaxant effect of the cyclic AMP selective PDE-inhibitors, while the nonselective methylxanthines did not show tachyphylaxis. The effect of theophylline was antagonized by low concentrations of adenosine, which by itself caused a weak tracheal contraction. The effect of PDI-inhibitors can be partly explained by decreased cyclic AMP breakdown but other mechanisms, such as antagonism of endogenous adenosine, may contribute to the observed relaxant action."}
{"id": "PMID:231893", "title": "Tryptophylglycine dipeptide in ACTH/MSH cells of the human hypophysis: its identification and studies on its antinociceptive effects in mice.", "content": "The ACTH/MSH cells of the pars distalis and pars intermedia of the mammalian hypophysis contain peptides with amino-terminal tryptophan which exhibit a strong fluorescence after treatment with modified formaldehyde vapour methods and with glyoxylic acid in the tissue sections from freeze-dried specimens. By homogenization of the hypophyses in ethanolic glyoxylic acid and subsequent heating the peptides can be converted to highly fluorescent beta-carboline derivatives; these can then be extracted with glacial acetic acid, separated by silica gel thin-layer chromatography and identified in UV light. Amino-terminal tryptophyl peptide from adult human hypophysis extracted and treated in this way gave the structure L-tryptophylglycine after acid hydrolysis. This structure was subsequently confirmed by producing a fluorescent derivative from authentic L-tryptophylglycine using the same reaction conditions as for the tissue homogenate. This derivative moved in the same way in thin-layer chromatography as fluorecent amino-terminal tryptophyl peptide extracted from human hypophysis. Thereafter a study was made of the antinociceptive effects of authentic L-tryptophylglycine administered subcutaneously in mice both alone and together with morphine. L-tryptophylglycine had no antinociceptive effects alone and neither did it change morphine antinociception. Also it had no apparent effects on the behaviour of mice. Thus, ACTH/MSH cells contain a dipeptide whose physiological function differs from the effects of ACTH, MSH and endorphins.", "contents": "Tryptophylglycine dipeptide in ACTH/MSH cells of the human hypophysis: its identification and studies on its antinociceptive effects in mice. The ACTH/MSH cells of the pars distalis and pars intermedia of the mammalian hypophysis contain peptides with amino-terminal tryptophan which exhibit a strong fluorescence after treatment with modified formaldehyde vapour methods and with glyoxylic acid in the tissue sections from freeze-dried specimens. By homogenization of the hypophyses in ethanolic glyoxylic acid and subsequent heating the peptides can be converted to highly fluorescent beta-carboline derivatives; these can then be extracted with glacial acetic acid, separated by silica gel thin-layer chromatography and identified in UV light. Amino-terminal tryptophyl peptide from adult human hypophysis extracted and treated in this way gave the structure L-tryptophylglycine after acid hydrolysis. This structure was subsequently confirmed by producing a fluorescent derivative from authentic L-tryptophylglycine using the same reaction conditions as for the tissue homogenate. This derivative moved in the same way in thin-layer chromatography as fluorecent amino-terminal tryptophyl peptide extracted from human hypophysis. Thereafter a study was made of the antinociceptive effects of authentic L-tryptophylglycine administered subcutaneously in mice both alone and together with morphine. L-tryptophylglycine had no antinociceptive effects alone and neither did it change morphine antinociception. Also it had no apparent effects on the behaviour of mice. Thus, ACTH/MSH cells contain a dipeptide whose physiological function differs from the effects of ACTH, MSH and endorphins."}
{"id": "PMID:231894", "title": "Electron microscopic features of a brain tumor induced in hamster by BK virus, a human papova virus.", "content": "In order to locate the target cells for malignant transformation by BK virus (a human papova virus) in hamster brain, electron microscopic observation of tumor originally induced in hamster brain by BK virus was performed. With light microscopy, the BK virus-induced tumor (Vn 17) bore a close resemblance to human malignant ependymoma. Under the electron microscope, numerous microvilli and few cilia were visible on the surface of the tumor cells. These tumor cells were joined to each other by desmosomes. Gap junctions were not observed. Multilayered cuboidal cells were observed around the lumen and blood vessels in the tumor. With regard to fine structure, three types of Vn 17 cells were recognized; ependymal like cells, tanycytes with prominent cell processes, and undifferentiated cells with few cytoplasmic organelles. There was no basal lamina between the ependymal cells and the connective tissue stroma. The Vn 17 cells showed some similarity to the ultrastructural features of the epemdymal cells of newborn rabbits, suggesting that the target cells for Vn 17 may be cells related to ependyma. Malignant transformation of the cells would be initiated in the early stages after BK virus inoculation into the brain of newborn hamsters.", "contents": "Electron microscopic features of a brain tumor induced in hamster by BK virus, a human papova virus. In order to locate the target cells for malignant transformation by BK virus (a human papova virus) in hamster brain, electron microscopic observation of tumor originally induced in hamster brain by BK virus was performed. With light microscopy, the BK virus-induced tumor (Vn 17) bore a close resemblance to human malignant ependymoma. Under the electron microscope, numerous microvilli and few cilia were visible on the surface of the tumor cells. These tumor cells were joined to each other by desmosomes. Gap junctions were not observed. Multilayered cuboidal cells were observed around the lumen and blood vessels in the tumor. With regard to fine structure, three types of Vn 17 cells were recognized; ependymal like cells, tanycytes with prominent cell processes, and undifferentiated cells with few cytoplasmic organelles. There was no basal lamina between the ependymal cells and the connective tissue stroma. The Vn 17 cells showed some similarity to the ultrastructural features of the epemdymal cells of newborn rabbits, suggesting that the target cells for Vn 17 may be cells related to ependyma. Malignant transformation of the cells would be initiated in the early stages after BK virus inoculation into the brain of newborn hamsters."}
{"id": "PMID:231900", "title": "Differentiation of the musculature of the teleost Brachydanio rerio. II. Effects of immobilization on the shape and structure of somites.", "content": "The development of the shape and structure of somites in the teleost Brachydanio rerio was studied in embryos under normal conditions and in immobilized embryos. Three different immobilization methods were applied: enclosure in agar, a glass rod in the neural tube and anaesthesia in MS-222. When the performance of the lateral body movements is prevented, the shape development of the somites in embryos and young larvae becomes reversed. When the agar-immobilization is terminated, the larvae resume their normal movements. In about 10 days, the shape of the somites is again as in control larvae. We conclude, that the lateral body movements have both a shape-determining and a shape-stabilizing role during the early stages of somite morphogenesis. It is suggested that in normal embryos differences in shortening between lateral and medial muscle fibres, cause differences in longitudinal growth of the muscle fibres and that the oblique muscle fibre arrangement is a consequence of these differences in growth. In immobilized embryos and larvae, the longitudinal growth of the muscle fibres is decreased. Also the difference in the longitudinal growth rate between lateral and medial muscle fibres diminishes in all somites. We conclude that for the normal morphogenesis of the somites the performance of the specific function, that is to bring about lateral body movements, is required. We suggest, that the impact of the lateral body movements on the development of the structure of the somites is mediated through adaptive growth of the muscle fibres. The suggestion may also apply to the development of the pinnate structure of muscles of higher vertebrates.", "contents": "Differentiation of the musculature of the teleost Brachydanio rerio. II. Effects of immobilization on the shape and structure of somites. The development of the shape and structure of somites in the teleost Brachydanio rerio was studied in embryos under normal conditions and in immobilized embryos. Three different immobilization methods were applied: enclosure in agar, a glass rod in the neural tube and anaesthesia in MS-222. When the performance of the lateral body movements is prevented, the shape development of the somites in embryos and young larvae becomes reversed. When the agar-immobilization is terminated, the larvae resume their normal movements. In about 10 days, the shape of the somites is again as in control larvae. We conclude, that the lateral body movements have both a shape-determining and a shape-stabilizing role during the early stages of somite morphogenesis. It is suggested that in normal embryos differences in shortening between lateral and medial muscle fibres, cause differences in longitudinal growth of the muscle fibres and that the oblique muscle fibre arrangement is a consequence of these differences in growth. In immobilized embryos and larvae, the longitudinal growth of the muscle fibres is decreased. Also the difference in the longitudinal growth rate between lateral and medial muscle fibres diminishes in all somites. We conclude that for the normal morphogenesis of the somites the performance of the specific function, that is to bring about lateral body movements, is required. We suggest, that the impact of the lateral body movements on the development of the structure of the somites is mediated through adaptive growth of the muscle fibres. The suggestion may also apply to the development of the pinnate structure of muscles of higher vertebrates."}
{"id": "PMID:231904", "title": "The role of cyclic AMP and cyclic GMP in byssinosis.", "content": "The lungs of female guinea pigs, either untreated or previously sensitized with aqueous extracts of cotton dust (AECD) were perfused via the pulmonary artery with 0, 10-6, 10-5 or 10-4 g/mL of lyophilized AECD in Tyrodes solution. Pressure changes in the pulmonary artery were monitored during this period. After perfusion, the pulmonary parenchyma was excised, frozen, and later analyzed for c-AMP, c-GMP, histamine, and total protein. Levels of c-AMP and histamine decreased while levels of c-GMP and pulmonary arterial pressure increased with increasing doses of AECD. Correlation coefficients, between the parameters measured, indicate that the ratio of c-AMP to c-GMP (c-AMP/c-GMP) was a better indicator of histamine depletion or change in pulmonary arterial pressure than was the level of either c-AMP or c-GMP alone. Comparisons of the relative changes in c-AMP, c-GMP, c-AMP/c-GMP, histamine, and pulmonary arterial pressure between sensitized and nonsensitized guinea pigs support the hypothesis that the acute changes in pulmonary function that follow breathing of cotton dust are due to the effects of pharmacoactive compounds and not to antigen-antibody response.", "contents": "The role of cyclic AMP and cyclic GMP in byssinosis. The lungs of female guinea pigs, either untreated or previously sensitized with aqueous extracts of cotton dust (AECD) were perfused via the pulmonary artery with 0, 10-6, 10-5 or 10-4 g/mL of lyophilized AECD in Tyrodes solution. Pressure changes in the pulmonary artery were monitored during this period. After perfusion, the pulmonary parenchyma was excised, frozen, and later analyzed for c-AMP, c-GMP, histamine, and total protein. Levels of c-AMP and histamine decreased while levels of c-GMP and pulmonary arterial pressure increased with increasing doses of AECD. Correlation coefficients, between the parameters measured, indicate that the ratio of c-AMP to c-GMP (c-AMP/c-GMP) was a better indicator of histamine depletion or change in pulmonary arterial pressure than was the level of either c-AMP or c-GMP alone. Comparisons of the relative changes in c-AMP, c-GMP, c-AMP/c-GMP, histamine, and pulmonary arterial pressure between sensitized and nonsensitized guinea pigs support the hypothesis that the acute changes in pulmonary function that follow breathing of cotton dust are due to the effects of pharmacoactive compounds and not to antigen-antibody response."}
{"id": "PMID:231905", "title": "Metastatic carcinoma presenting as fulminant hepatic failure.", "content": "An unusual cause of fulminant hepatic failure is described. The patient, who presented with symptoms of liver disease, proved to have a small primary oat cell carcinoma of the lung with massive hepatic metastases. The clinical evolution was rapid, with marked elevations of SGOT (this without a prior hypotensive episode) and hepatic coma. Examination of the liver showed two types of necrosis: 1. infarction secondary to multiple tumor emboli in portal vessels and 2. overrunning of hepatic cell plates by expanding masses of tumor cells (somewhat analogous to piecemeal necrosis).", "contents": "Metastatic carcinoma presenting as fulminant hepatic failure. An unusual cause of fulminant hepatic failure is described. The patient, who presented with symptoms of liver disease, proved to have a small primary oat cell carcinoma of the lung with massive hepatic metastases. The clinical evolution was rapid, with marked elevations of SGOT (this without a prior hypotensive episode) and hepatic coma. Examination of the liver showed two types of necrosis: 1. infarction secondary to multiple tumor emboli in portal vessels and 2. overrunning of hepatic cell plates by expanding masses of tumor cells (somewhat analogous to piecemeal necrosis)."}
{"id": "PMID:231907", "title": "Partial trisomy 20 confirmed by gene dosage studies.", "content": "We describe a female infant with multiple congenital anomalies and mental retardation, pre- and postnatal growth failure, microcephaly, unusual facial appearance, and minor skeletal anomalies, all very suggestive of the partial trisomy 20(p) syndrome. Although she was born to karyotypically normal parents, she had an extra small metacentric chromosome. Analysis of metaphase and prometaphase chromosomes by GTG banding and Giemsa 11 staining showed that the extra chromosome was a number 20 with a deletion of the distal end of the long arm. Gene dose studies of adenosine deaminase (ADA) and inosine triphosphatase (ITP) supported the cytogenetic interpretation.", "contents": "Partial trisomy 20 confirmed by gene dosage studies. We describe a female infant with multiple congenital anomalies and mental retardation, pre- and postnatal growth failure, microcephaly, unusual facial appearance, and minor skeletal anomalies, all very suggestive of the partial trisomy 20(p) syndrome. Although she was born to karyotypically normal parents, she had an extra small metacentric chromosome. Analysis of metaphase and prometaphase chromosomes by GTG banding and Giemsa 11 staining showed that the extra chromosome was a number 20 with a deletion of the distal end of the long arm. Gene dose studies of adenosine deaminase (ADA) and inosine triphosphatase (ITP) supported the cytogenetic interpretation."}
{"id": "PMID:231908", "title": "Small cell carcinoma of the lung and its histological origin. Report of a case.", "content": "A rare lung cancer consisting in part of small cell carcinoma of intermediate cell type and in part of well-differentiated papillotubular adenocarcinoma is described. Alcian blue-PAS staining was observed in the cytoplasm of the small cell carcinoma cells; the Grimelius argyrophil reaction was also positive in the cytoplasm of these cells. Electron microscopy revealed neurosecretory granules in the cytoplasm. At autopsy, a small cell carcinoma of intermediate cell type was found with both squamous features and gland formation. The cellularity and histological pattern of this tumor suggested the existence of a transitional pattern between small cell carcinoma of intermediate cell type, squamous cell carcinoma and adenocarcinoma. From the above findings, we think that small cell carcinoma including the intermediate cell type is derived from respiratory epithelial cells of endodermal origin with dedifferentiation of those cancer cells into neurosecretory cells.", "contents": "Small cell carcinoma of the lung and its histological origin. Report of a case. A rare lung cancer consisting in part of small cell carcinoma of intermediate cell type and in part of well-differentiated papillotubular adenocarcinoma is described. Alcian blue-PAS staining was observed in the cytoplasm of the small cell carcinoma cells; the Grimelius argyrophil reaction was also positive in the cytoplasm of these cells. Electron microscopy revealed neurosecretory granules in the cytoplasm. At autopsy, a small cell carcinoma of intermediate cell type was found with both squamous features and gland formation. The cellularity and histological pattern of this tumor suggested the existence of a transitional pattern between small cell carcinoma of intermediate cell type, squamous cell carcinoma and adenocarcinoma. From the above findings, we think that small cell carcinoma including the intermediate cell type is derived from respiratory epithelial cells of endodermal origin with dedifferentiation of those cancer cells into neurosecretory cells."}
{"id": "PMID:231909", "title": "Localization of myoglobin in normal and neoplastic human skeletal muscle cells using an immunoperoxidase method.", "content": "Using an immunoperoxidase method, myoglobin is localized in the cytoplasm of normal and neoplastic human skeletal muscle. The staining intensity is variable in individual cells. This can be explained by the variable concentration of myoglobin in the different fiber types of normal muscle or the different degree of differentiation in neoplastic muscle cells, respectively. A potential application of this method in tumor pathology is discussed in connection with myoglobin as a tissue-specific marker for skeletal muscle neoplasms.", "contents": "Localization of myoglobin in normal and neoplastic human skeletal muscle cells using an immunoperoxidase method. Using an immunoperoxidase method, myoglobin is localized in the cytoplasm of normal and neoplastic human skeletal muscle. The staining intensity is variable in individual cells. This can be explained by the variable concentration of myoglobin in the different fiber types of normal muscle or the different degree of differentiation in neoplastic muscle cells, respectively. A potential application of this method in tumor pathology is discussed in connection with myoglobin as a tissue-specific marker for skeletal muscle neoplasms."}
{"id": "PMID:231906", "title": "Hormone producing pancreatic islet cell carcinoma: changing clinical presentation.", "content": "A patient with pancreatic islet cell carcinoma demonstrated spontaneous remission and recurrence of hyperinsulinism and disappearance of elevated plasma motilin levels. Despite evidence for gastrin production by the tumor initially, the Zollinger-Ellison syndrome was not diagnosed until three years after initial presentation. Diarrhea and steatorrhea could be attributed to hyperchlorhydria rather than to direct intestinal effects of elevated cirulating gastrin, gastric inhibitory peptide or motilin. Pancreatic islet cell carcinomas, considered as a type a APUD cell proliferation, frequently produce more than one hormone; the pattern of hormone secretion may differ with time and clinical manifestations may change accordingly.", "contents": "Hormone producing pancreatic islet cell carcinoma: changing clinical presentation. A patient with pancreatic islet cell carcinoma demonstrated spontaneous remission and recurrence of hyperinsulinism and disappearance of elevated plasma motilin levels. Despite evidence for gastrin production by the tumor initially, the Zollinger-Ellison syndrome was not diagnosed until three years after initial presentation. Diarrhea and steatorrhea could be attributed to hyperchlorhydria rather than to direct intestinal effects of elevated cirulating gastrin, gastric inhibitory peptide or motilin. Pancreatic islet cell carcinomas, considered as a type a APUD cell proliferation, frequently produce more than one hormone; the pattern of hormone secretion may differ with time and clinical manifestations may change accordingly."}
{"id": "PMID:231913", "title": "Prostaglandin mediated inflammatory changes induced by alpha-adrenoceptor stimulation in the sympathectomised rabbit eye.", "content": "Topical application of 50 microliter of 0.1% noradrenaline or 10% phenylepherine to either a surgically sympathectomised or a guanethidine treated rabbit eye induced a transient increase in intraocular pressure (IOP), between 90 and 150 min, followed by a fall to hypotensive levels. These changes were accompanied by the development of conjunctival and anterior uveal hyperemia and an aqueous flare. Fluorescein angiography and microscopic examination after intravenously injecting colloidal carbon showed that the major site of disruption of the blood-aqueous barrier occurs in the ciliary processes. Slightly elevated levels of protein and prostaglandin-like activity (PG) were detected in aqueous samples withdrawn 3 or 5 h after application of either adrenergic agent. Prior treatment with indomethacin or phentolamine prevented the ocular hypertensive phase as well as the inflammatory changes, suggesting that the inflammatory rebound is mediated by PG and that PG release under such circumstances is closely linked to alpha-adrenoceptor activation. By contrast, the rise in IOP occurring after each of several successive daily applications of an alpha-agonist to a normal rabbit eye was not accompanied by hyperemia or an aqueous flare and was not inhibited by indomethacin pretreatment.", "contents": "Prostaglandin mediated inflammatory changes induced by alpha-adrenoceptor stimulation in the sympathectomised rabbit eye. Topical application of 50 microliter of 0.1% noradrenaline or 10% phenylepherine to either a surgically sympathectomised or a guanethidine treated rabbit eye induced a transient increase in intraocular pressure (IOP), between 90 and 150 min, followed by a fall to hypotensive levels. These changes were accompanied by the development of conjunctival and anterior uveal hyperemia and an aqueous flare. Fluorescein angiography and microscopic examination after intravenously injecting colloidal carbon showed that the major site of disruption of the blood-aqueous barrier occurs in the ciliary processes. Slightly elevated levels of protein and prostaglandin-like activity (PG) were detected in aqueous samples withdrawn 3 or 5 h after application of either adrenergic agent. Prior treatment with indomethacin or phentolamine prevented the ocular hypertensive phase as well as the inflammatory changes, suggesting that the inflammatory rebound is mediated by PG and that PG release under such circumstances is closely linked to alpha-adrenoceptor activation. By contrast, the rise in IOP occurring after each of several successive daily applications of an alpha-agonist to a normal rabbit eye was not accompanied by hyperemia or an aqueous flare and was not inhibited by indomethacin pretreatment."}
{"id": "PMID:231918", "title": "Surgical approach to retromandibular parotid tumors.", "content": "Because of the anatomy of the deep lobe of the parotid and its restrictive boundaries, retromandibular tumors may be asymptomatic until reaching massive size. Removal by an intraoral approach may be not only disappointing but also disastrous, with disintegration of the tumor and generalized spillage in the wound. Our experience suggests that the best approach to any type of tumor in this region is through the upper lateral cervical tissues with consideration of a mandibular osteotomy if the tumor extends into the retropharynx or the nasopharynx. This review of 12 patients who required osteotomy describes a high success rate with minimal complications.", "contents": "Surgical approach to retromandibular parotid tumors. Because of the anatomy of the deep lobe of the parotid and its restrictive boundaries, retromandibular tumors may be asymptomatic until reaching massive size. Removal by an intraoral approach may be not only disappointing but also disastrous, with disintegration of the tumor and generalized spillage in the wound. Our experience suggests that the best approach to any type of tumor in this region is through the upper lateral cervical tissues with consideration of a mandibular osteotomy if the tumor extends into the retropharynx or the nasopharynx. This review of 12 patients who required osteotomy describes a high success rate with minimal complications."}
{"id": "PMID:231919", "title": "Locally recurrent carcinoma after breast reconstruction.", "content": "The incidence of locally recurrent carcinoma after mastectomy is low--between 6 and 20%. Recent case histories of 4 patients who were clinically free of breast carcinoma and who developed local recurrence after reconstruction are reviewed. Possible relationships of breast reconstruction to local recurrence are discussed. The development of capsule formation in the reconstructed breast may denote recurrent disease.", "contents": "Locally recurrent carcinoma after breast reconstruction. The incidence of locally recurrent carcinoma after mastectomy is low--between 6 and 20%. Recent case histories of 4 patients who were clinically free of breast carcinoma and who developed local recurrence after reconstruction are reviewed. Possible relationships of breast reconstruction to local recurrence are discussed. The development of capsule formation in the reconstructed breast may denote recurrent disease."}
{"id": "PMID:231914", "title": "Nitroprusside and the duration of tubocurarine and pancuronium.", "content": "Seventy-six patients in whom sodium nitroprusside was administered in order to induce hypotension received either 0.2 mg/kg tubocurarine or 0.04 mg/kg pancuronium bromide. The duration of action of these two drugs was assessed. In contrast to previous studies in the dog, sodium nitroprusside, given concurrently with either tubocurarine or pancuronium bromide, did not result in significantly prolonged neuromuscular blockade (33.0 vs 28.6 min for tubocurarine and 39.3 vs 39.6 min for pancuronium bromide; P greater than 0.1). These findings suggest that the prolonged neuromuscular blockade which is sometimes associated with trimetaphan-induced hypotension in man, is not encountered with sodium nitroprusside.", "contents": "Nitroprusside and the duration of tubocurarine and pancuronium. Seventy-six patients in whom sodium nitroprusside was administered in order to induce hypotension received either 0.2 mg/kg tubocurarine or 0.04 mg/kg pancuronium bromide. The duration of action of these two drugs was assessed. In contrast to previous studies in the dog, sodium nitroprusside, given concurrently with either tubocurarine or pancuronium bromide, did not result in significantly prolonged neuromuscular blockade (33.0 vs 28.6 min for tubocurarine and 39.3 vs 39.6 min for pancuronium bromide; P greater than 0.1). These findings suggest that the prolonged neuromuscular blockade which is sometimes associated with trimetaphan-induced hypotension in man, is not encountered with sodium nitroprusside."}
{"id": "PMID:231920", "title": "Factorial experimental design applied to the immunological study of two foot-and-mouth disease virus subtypes. 2. Theoretical study of experimental models.", "content": "A certain number of theoretical models of immunological relations that 2 foot-and-mouth disease viruses can support, were constructed so as to discuss in each case, the results of the factorial analysis of the data. This method provided a specific answer to each of the questions that were asked in the presence of a test of this kind. The results obtained with several immunological cross-tests comparable to that of the A Greece 69-A Allier viruses, illustrated most of the theoretical models.", "contents": "Factorial experimental design applied to the immunological study of two foot-and-mouth disease virus subtypes. 2. Theoretical study of experimental models. A certain number of theoretical models of immunological relations that 2 foot-and-mouth disease viruses can support, were constructed so as to discuss in each case, the results of the factorial analysis of the data. This method provided a specific answer to each of the questions that were asked in the presence of a test of this kind. The results obtained with several immunological cross-tests comparable to that of the A Greece 69-A Allier viruses, illustrated most of the theoretical models."}
{"id": "PMID:231921", "title": "[Feedstuffs contamination by Penicillium cyclopium Westling. Frequency of penicillic acid producing strains (author's transl)].", "content": "For the last six years, 246 samples of feedstuffs, suspected for animal disorder, have been subjected to mycological examination, Penicillium cyclopium was present with more than 10(3) and 10(5) propagules per gram respectively in 42% and 6% of samples. The feeds mainly concerned are, in decreasing order of P. cyclopium frequency and contamination level : barley, ma\u00efze mixed feeds (50%), the straw (41%), hays (21%) and milk replacers (10%) (table 1). The penicillic acid bioproduction by fifty strains freshly isolated from these feedstuffs is investigated on wet crushed corn (60% water). After incubation at 25 degrees C for a week, extraction by ethyl acetate and purification, quantification is done by fluorodensitometry on TLC plates after exposure to concentrated ammonia (fig. 1). Among the strains, 50% produces less than 5 ppm, 4% between 10-100 ppm, 20% (100-1 000), 20% (1 000-5 000) and 6% (5 000-10 000 ppm) (table 2). Maximal yield obtained was 8 240 mg/kg. Hypothesis of a log-normal distribution of toxigenic strength is not rejected (fig. 2). On the whole, frequency and toxic yields are higher for strains originating from cereals. One may think that only a quarter of the strains might be considered as actual potential penicillic acid producers in agricultural conditions.", "contents": "[Feedstuffs contamination by Penicillium cyclopium Westling. Frequency of penicillic acid producing strains (author's transl)]. For the last six years, 246 samples of feedstuffs, suspected for animal disorder, have been subjected to mycological examination, Penicillium cyclopium was present with more than 10(3) and 10(5) propagules per gram respectively in 42% and 6% of samples. The feeds mainly concerned are, in decreasing order of P. cyclopium frequency and contamination level : barley, ma\u00efze mixed feeds (50%), the straw (41%), hays (21%) and milk replacers (10%) (table 1). The penicillic acid bioproduction by fifty strains freshly isolated from these feedstuffs is investigated on wet crushed corn (60% water). After incubation at 25 degrees C for a week, extraction by ethyl acetate and purification, quantification is done by fluorodensitometry on TLC plates after exposure to concentrated ammonia (fig. 1). Among the strains, 50% produces less than 5 ppm, 4% between 10-100 ppm, 20% (100-1 000), 20% (1 000-5 000) and 6% (5 000-10 000 ppm) (table 2). Maximal yield obtained was 8 240 mg/kg. Hypothesis of a log-normal distribution of toxigenic strength is not rejected (fig. 2). On the whole, frequency and toxic yields are higher for strains originating from cereals. One may think that only a quarter of the strains might be considered as actual potential penicillic acid producers in agricultural conditions."}
{"id": "PMID:231922", "title": "[Serologic detection of rotavirus infection in swine from the region of Brittany (author's transl)].", "content": "Indirect immunofluorescence (micromethod) was used to detect antirotavirus antibodies. Sera (166) were collected on adult pigs at slaughterhouse in the following french departments: Finistere, Morbihan and Ille et Vilaine. Antibodies were detected in 83% of the samples.", "contents": "[Serologic detection of rotavirus infection in swine from the region of Brittany (author's transl)]. Indirect immunofluorescence (micromethod) was used to detect antirotavirus antibodies. Sera (166) were collected on adult pigs at slaughterhouse in the following french departments: Finistere, Morbihan and Ille et Vilaine. Antibodies were detected in 83% of the samples."}
{"id": "PMID:231923", "title": "Factorial experimental design applied to the immunological study of two foot-and-mouth disease virus subtypes. 1. A Greece 1969 -- A Allier example.", "content": "A double immunological cross-test, carried out with the index K method, is subjected to a statistical analysis by a factorial experiment. The A Greece and A Allier viruses, which have been taken as an example of the calculations procedure, seem to be in 2 immunologically different subtypes.", "contents": "Factorial experimental design applied to the immunological study of two foot-and-mouth disease virus subtypes. 1. A Greece 1969 -- A Allier example. A double immunological cross-test, carried out with the index K method, is subjected to a statistical analysis by a factorial experiment. The A Greece and A Allier viruses, which have been taken as an example of the calculations procedure, seem to be in 2 immunologically different subtypes."}
{"id": "PMID:231927", "title": "The biology of affective disorders.", "content": "The clinical features, genetic data, psychopharmacological studies, hormonal abnormalities, and biochemical observations all serve to define major depressive illness as an inherited neurochemical disorder affecting the hypothalamus, and probably involving monoamine pathways. While the precise nature of the defect and its mode of transmission remain obscure, the rapid development of this field in less than two decades permits optimism that major depressive illness illness will be among the first \"functional\" psychiatric disorders to have its chemical pathology elucidated.", "contents": "The biology of affective disorders. The clinical features, genetic data, psychopharmacological studies, hormonal abnormalities, and biochemical observations all serve to define major depressive illness as an inherited neurochemical disorder affecting the hypothalamus, and probably involving monoamine pathways. While the precise nature of the defect and its mode of transmission remain obscure, the rapid development of this field in less than two decades permits optimism that major depressive illness illness will be among the first \"functional\" psychiatric disorders to have its chemical pathology elucidated."}
{"id": "PMID:231934", "title": "Modified procedure for the recovery of naturally accumulated poliovirus from oysters.", "content": "Methods were compared for their ability to recover poliovirus from oysters (Crassostrea gigas) which had been allowed to accumulate virus via normal filtration activities. Clarification procedures included glycine-NaCl and polyelectrolyte extraction methods followed by a variety of acid precipitation concentration methods. Polyelectrolyte flocculation followed by a beef extract-supplemented acid precipitation carried out at pH 3.5 yielded the most efficient recoveries. Direct assay of homogenates was found to be an unreliable method for determining the initial virus concentration in \"naturally infected\" oysters.", "contents": "Modified procedure for the recovery of naturally accumulated poliovirus from oysters. Methods were compared for their ability to recover poliovirus from oysters (Crassostrea gigas) which had been allowed to accumulate virus via normal filtration activities. Clarification procedures included glycine-NaCl and polyelectrolyte extraction methods followed by a variety of acid precipitation concentration methods. Polyelectrolyte flocculation followed by a beef extract-supplemented acid precipitation carried out at pH 3.5 yielded the most efficient recoveries. Direct assay of homogenates was found to be an unreliable method for determining the initial virus concentration in \"naturally infected\" oysters."}
{"id": "PMID:231935", "title": "Viral heat resistance and infectious ribonucleic acid.", "content": "High-titer suspensions of poliovirus 1 and coxsackievirus B-2 were shown to contain a heat-resistant fraction when heated for 65 min at temperature ranging from 56 to 70 degrees C. The addition of ribonuclease to the heated suspensions eliminated plaque production in the cell cultures, indicating that the resistant fraction was infectious ribonucleic acid that had been liberated from ruptured viruses during the heating process.", "contents": "Viral heat resistance and infectious ribonucleic acid. High-titer suspensions of poliovirus 1 and coxsackievirus B-2 were shown to contain a heat-resistant fraction when heated for 65 min at temperature ranging from 56 to 70 degrees C. The addition of ribonuclease to the heated suspensions eliminated plaque production in the cell cultures, indicating that the resistant fraction was infectious ribonucleic acid that had been liberated from ruptured viruses during the heating process."}
{"id": "PMID:231936", "title": "Adsorption of enteroviruses to soil cores and their subsequent elution by artificial rainwater.", "content": "The adsorption and elution of a variety of human enteroviruses in a highly permeable, sandy soil was studied by using cores (43 by 125 mm) collected from an operating recharge basin on Long Island. Viruses studied included field and reference strains of polioviruses types 1 and 3 and reference strains of coxsackie virus B3 and echovirus types 1 and 6. Viruses suspended in treated sewage effluent were allowed to percolate through soil cores, and the filtrate was assayed for unadsorbed viruses. To determine the likelihood of desorption and mobilization, soil-bound viruses were subjected to a rinse with either treated sewage effluent or simulated rainwater which reflected the anion, cation, and pH characteristics of a typical northeastern United States rainfall. The results demonstrated that all polioviruses tested, including both reference and field strains, adsorbed extremely well to cores. Adsorption was somewhat reduced when clean, unconditioned soils were used. Soil-bound poliovirus strain LSc was not significantly mobilized by flooding columns with either a sewage effluent or rainwater rinse. One virus was mobilized by both types of rinses. The amount of viruses mobilized by rainwater rinses ranged from 24 to 66%. Variable adsorption-elution results were observed with other enteroviruses. Two guanidine-resistant mutants of poliovirus LSc demonstrated a soil adsorption-elution profile different from that of the parent strain. The data support the conclusion that soil adsorption-elution behavior is strain dependent and that poliovirus, particularly strain LSc, represents an inappropriate model.", "contents": "Adsorption of enteroviruses to soil cores and their subsequent elution by artificial rainwater. The adsorption and elution of a variety of human enteroviruses in a highly permeable, sandy soil was studied by using cores (43 by 125 mm) collected from an operating recharge basin on Long Island. Viruses studied included field and reference strains of polioviruses types 1 and 3 and reference strains of coxsackie virus B3 and echovirus types 1 and 6. Viruses suspended in treated sewage effluent were allowed to percolate through soil cores, and the filtrate was assayed for unadsorbed viruses. To determine the likelihood of desorption and mobilization, soil-bound viruses were subjected to a rinse with either treated sewage effluent or simulated rainwater which reflected the anion, cation, and pH characteristics of a typical northeastern United States rainfall. The results demonstrated that all polioviruses tested, including both reference and field strains, adsorbed extremely well to cores. Adsorption was somewhat reduced when clean, unconditioned soils were used. Soil-bound poliovirus strain LSc was not significantly mobilized by flooding columns with either a sewage effluent or rainwater rinse. One virus was mobilized by both types of rinses. The amount of viruses mobilized by rainwater rinses ranged from 24 to 66%. Variable adsorption-elution results were observed with other enteroviruses. Two guanidine-resistant mutants of poliovirus LSc demonstrated a soil adsorption-elution profile different from that of the parent strain. The data support the conclusion that soil adsorption-elution behavior is strain dependent and that poliovirus, particularly strain LSc, represents an inappropriate model."}
{"id": "PMID:231937", "title": "Procedure for the recovery of airborne human enteric viruses during spray irrigation of treated wastewater.", "content": "Because of the relatively low number of indigenous enteric viruses recovered from secondary wastewater effluents, their presence in air (aerosols) as a result of wastewater spray irrigation requires extensive sampling. Methodology to allow the recovery of indigenous enteroviruses from aerosols generated at an operational wastewater irrigation site was tested under both laboratory and field conditions.", "contents": "Procedure for the recovery of airborne human enteric viruses during spray irrigation of treated wastewater. Because of the relatively low number of indigenous enteric viruses recovered from secondary wastewater effluents, their presence in air (aerosols) as a result of wastewater spray irrigation requires extensive sampling. Methodology to allow the recovery of indigenous enteroviruses from aerosols generated at an operational wastewater irrigation site was tested under both laboratory and field conditions."}
{"id": "PMID:231938", "title": "Structural changes associated with poliovirus inactivation in soil.", "content": "The loss of infectivity of poliovirus in moist and dried soils was a result of irreversible damage to the virus particles. The damage included (i) dissociation of viral genomes and capsids and (ii) degradation of viral ribonucleic acid (RNA) in the soil environment. Under drying conditions, capsid components could not be recovered from the soils. Further studies in sterile soils indicated that, under moist conditions, the viral RNA was probably damaged before dissociation from the capsid. However, in sterile, dried soil, RNA genomes were recovered largely intact from the soil. These results suggest that polioviruses are inactivated by different mechanisms in moist and drying soils.", "contents": "Structural changes associated with poliovirus inactivation in soil. The loss of infectivity of poliovirus in moist and dried soils was a result of irreversible damage to the virus particles. The damage included (i) dissociation of viral genomes and capsids and (ii) degradation of viral ribonucleic acid (RNA) in the soil environment. Under drying conditions, capsid components could not be recovered from the soils. Further studies in sterile soils indicated that, under moist conditions, the viral RNA was probably damaged before dissociation from the capsid. However, in sterile, dried soil, RNA genomes were recovered largely intact from the soil. These results suggest that polioviruses are inactivated by different mechanisms in moist and drying soils."}
{"id": "PMID:231939", "title": "In vivo effect of the Syndets Idet 5L and Swanic 6L ON ATPase activity in the teleost, Channa punctatus.", "content": "Channa punctatus were exposed to various sub-lethal concentrations of Idet 5L and Swanic 6L for 25 and 50 days. Brain and gill homogenates were analyzed for enzyme activity from treated and untreated fish. Enzyme inhibitions were highest in oligomycin-insensitive Mg++ ATPase, with pronounced effects (over 65% inhibition) after 50 days exposure of fish to 7.5 mg/L concentration of Swanic 6L. Fish exposed to lowest concentrations of syndets showed an insignificant activation of Na+-K+ and oligomycin-sensitive Mg++ ATPases in the gill.", "contents": "In vivo effect of the Syndets Idet 5L and Swanic 6L ON ATPase activity in the teleost, Channa punctatus. Channa punctatus were exposed to various sub-lethal concentrations of Idet 5L and Swanic 6L for 25 and 50 days. Brain and gill homogenates were analyzed for enzyme activity from treated and untreated fish. Enzyme inhibitions were highest in oligomycin-insensitive Mg++ ATPase, with pronounced effects (over 65% inhibition) after 50 days exposure of fish to 7.5 mg/L concentration of Swanic 6L. Fish exposed to lowest concentrations of syndets showed an insignificant activation of Na+-K+ and oligomycin-sensitive Mg++ ATPases in the gill."}
{"id": "PMID:231943", "title": "NADH-dependent reduction of D-proline in Clostridium sticklandii. Reconstitution from three fractions containing NADH dehydrogenase, D-proline reductase, and a third protein factor.", "content": "The enzyme system from Clostridium sticklandii catalyzing the NADH-dependent reduction of D-proline was co-purified by chromatography on DEAE-cellulose at pH 8.2 and ammonium sulfate fractionation, and resolved into fractions containing three different protein components, NADH dehydrogenase, D-proline reductase and a third protein factor, by chromatography on DEAE-cellulose at pH 7.0. Upon recombination of the fractions containing the three different protein components, the NADH-dependent reduction of D-proline was successfully reconstituted. The NADH dehydrogenase fractions oxidized NADH in the presence of artificial electron acceptors, and were inhibited by p-hydroxymercuriphenylsulfonate (50% at 80 nM). They contained 3--4 different enzyme bands as revealed by polyacrylamide-gel electropherograms stained with the NADH-dependent reduction of 2,3,5-triphenyltetrazolium chloride. D-Proline reduction was also coupled to a leuco-methylene blue-generating system containing D-glucose and glucose-oxidase (EC 1.1.3.4). Circumstantial evidence indicated that, among the clostridial proteins, only D-proline reductase and the third protein factor were needed for this reaction.", "contents": "NADH-dependent reduction of D-proline in Clostridium sticklandii. Reconstitution from three fractions containing NADH dehydrogenase, D-proline reductase, and a third protein factor. The enzyme system from Clostridium sticklandii catalyzing the NADH-dependent reduction of D-proline was co-purified by chromatography on DEAE-cellulose at pH 8.2 and ammonium sulfate fractionation, and resolved into fractions containing three different protein components, NADH dehydrogenase, D-proline reductase and a third protein factor, by chromatography on DEAE-cellulose at pH 7.0. Upon recombination of the fractions containing the three different protein components, the NADH-dependent reduction of D-proline was successfully reconstituted. The NADH dehydrogenase fractions oxidized NADH in the presence of artificial electron acceptors, and were inhibited by p-hydroxymercuriphenylsulfonate (50% at 80 nM). They contained 3--4 different enzyme bands as revealed by polyacrylamide-gel electropherograms stained with the NADH-dependent reduction of 2,3,5-triphenyltetrazolium chloride. D-Proline reduction was also coupled to a leuco-methylene blue-generating system containing D-glucose and glucose-oxidase (EC 1.1.3.4). Circumstantial evidence indicated that, among the clostridial proteins, only D-proline reductase and the third protein factor were needed for this reaction."}
{"id": "PMID:231946", "title": "The effects of ultraviolet and ionizing radiation on herpesviruses, SV40 and adenoviruses in relation to the small-plaque effect.", "content": "The small-plaque effect occurs with a wide range of herpesviruses following irradiation with ultraviolet light. The 37 per cent survival (D37) values, or dose required for one lethal hit (e-1), for herpes simplex, pseudorabies and pigeon herpesviruses in different cells indicate a broad spectrum of host-cell repair capacity. Other DNA-containing viruses such as SV40 and adenoviruses, which also replicate in the cell nucleus, show the small-plaque effect. Ionizing irradiation of herpes simplex virus type 1 (HSV-1) showed but little reduction in plaque-size.", "contents": "The effects of ultraviolet and ionizing radiation on herpesviruses, SV40 and adenoviruses in relation to the small-plaque effect. The small-plaque effect occurs with a wide range of herpesviruses following irradiation with ultraviolet light. The 37 per cent survival (D37) values, or dose required for one lethal hit (e-1), for herpes simplex, pseudorabies and pigeon herpesviruses in different cells indicate a broad spectrum of host-cell repair capacity. Other DNA-containing viruses such as SV40 and adenoviruses, which also replicate in the cell nucleus, show the small-plaque effect. Ionizing irradiation of herpes simplex virus type 1 (HSV-1) showed but little reduction in plaque-size."}
{"id": "PMID:231947", "title": "Factors affecting the growth and titration by immunofluorescence of simian foamy virus.", "content": "This paper presents some observations concerned with the growth of simian foamy virus and some modifications which should be introduced to the fluorescence assay of foamy virus. The modified procedure is the most sensitive method described for the titration of foamy virus. Examination of the optimal conditions for the growth and titration by fluorescence assay of simian foamy virus showed that the virus was particularly sensitive to changes in virus and cell concentration. At the low cell concentrations employed previously a \"saturation-type\" response was obtained with high titre virus and virus adsorption efficiency was decreased as input virus was diluted. Maximum virus production was obtained with high cell concentrations at input multiplicities of 5 and 10. At high multiplicities of infection more than 90 per cent of the cells adsorbed virus but only 45 per cent became infected, this appeared to be related to cell DNA synthesis.", "contents": "Factors affecting the growth and titration by immunofluorescence of simian foamy virus. This paper presents some observations concerned with the growth of simian foamy virus and some modifications which should be introduced to the fluorescence assay of foamy virus. The modified procedure is the most sensitive method described for the titration of foamy virus. Examination of the optimal conditions for the growth and titration by fluorescence assay of simian foamy virus showed that the virus was particularly sensitive to changes in virus and cell concentration. At the low cell concentrations employed previously a \"saturation-type\" response was obtained with high titre virus and virus adsorption efficiency was decreased as input virus was diluted. Maximum virus production was obtained with high cell concentrations at input multiplicities of 5 and 10. At high multiplicities of infection more than 90 per cent of the cells adsorbed virus but only 45 per cent became infected, this appeared to be related to cell DNA synthesis."}
{"id": "PMID:231948", "title": "Experimental infection of mink with influenza A viruses. Brief report.", "content": "Mink were found to be susceptible to the intranasal inoculation of human, swine, equine and avian influenza A viruses. The viruses were recovered until the 7th post inoculation (p.i.) day from the respiratory tract. The inoculated mink showed antibody response against these viruses. Contact infection in mink with A/Kumamoto/22/77 (H3N2) was possible.", "contents": "Experimental infection of mink with influenza A viruses. Brief report. Mink were found to be susceptible to the intranasal inoculation of human, swine, equine and avian influenza A viruses. The viruses were recovered until the 7th post inoculation (p.i.) day from the respiratory tract. The inoculated mink showed antibody response against these viruses. Contact infection in mink with A/Kumamoto/22/77 (H3N2) was possible."}
{"id": "PMID:231949", "title": "Avian pox virus. An ultrastructural study on a cherrug falcon. Brief report.", "content": "The ultrastructure and maturation of avian pox particles is described in the rare case of a naturally infected hawk (Falco cherrug). As in other cells infected by fowlpox virus two types of inclusion bodies are encountered in the cytoplasm: firstly assemblies of fluffy filamentous material apparently giving rise to immature virions. They are thought to present virus factories (inclusion body B). Secondly mature virus particles budded into extensive groupings (Bollinger bodies, inclusion body A) which display a fine structure identical to other strains of fowlpox virus.", "contents": "Avian pox virus. An ultrastructural study on a cherrug falcon. Brief report. The ultrastructure and maturation of avian pox particles is described in the rare case of a naturally infected hawk (Falco cherrug). As in other cells infected by fowlpox virus two types of inclusion bodies are encountered in the cytoplasm: firstly assemblies of fluffy filamentous material apparently giving rise to immature virions. They are thought to present virus factories (inclusion body B). Secondly mature virus particles budded into extensive groupings (Bollinger bodies, inclusion body A) which display a fine structure identical to other strains of fowlpox virus."}
{"id": "PMID:231950", "title": "Serum lipoprotein lipids after gemfibrozil treatment.", "content": "The changes of serum lipoprotein lipids including the phospholipids of twelve hyperlipoproteinemic patients were studied after a four weeks treatment with 1200 mg/day gemfibrozil. There was a decrease of all VLDL lipids as well as of LDL and HDL triglycerides and an increase of HDL cholesterol. The phospholipids were influenced in different directions, particularly their concentration in the HDL was constant. The LDL/HDL lipid ratios remained elevated after gemfibrozil. To evaluate the effect of a hypolipidemic drug in more detail, the analysis of the complete lipoprotein lipid moiety and the ratios within and between the lipoproteins would be helpful.", "contents": "Serum lipoprotein lipids after gemfibrozil treatment. The changes of serum lipoprotein lipids including the phospholipids of twelve hyperlipoproteinemic patients were studied after a four weeks treatment with 1200 mg/day gemfibrozil. There was a decrease of all VLDL lipids as well as of LDL and HDL triglycerides and an increase of HDL cholesterol. The phospholipids were influenced in different directions, particularly their concentration in the HDL was constant. The LDL/HDL lipid ratios remained elevated after gemfibrozil. To evaluate the effect of a hypolipidemic drug in more detail, the analysis of the complete lipoprotein lipid moiety and the ratios within and between the lipoproteins would be helpful."}
{"id": "PMID:231951", "title": "Effects of oxandrolone on plasma lipoproteins in patients with type IIa, IIb and IV hyperlipoproteinemia: occurrence of hypo-high density lipoproteinemia.", "content": "The effects of oxandrolone on plasma lipids and lipoprotein composition in patients with type IIa, IIb and IV hyperlipoproteinemia were investigated. Oxandrolone (4 mg/day, for 28 days) induced a significant reduction in plasma and VLDL triglyceride. Reciprocal elevation of LDL cholesterol was observed in 8 of 10 type IV patients and in 2 of 5 type IIb patients. In patients with type IV hyperlipoproteinemia, significant reduction of plasma apolipoproteinB and VLDL apolipoprotein B and inverse LDL apolipoprotein B increment was observed after treatment with oxandrolone. HDL cholesterol was decreased. Hypo-high density lipoproteinemia defined as HDL cholesterol concentration below 40 mg/100 ml occurred in 7 of 10 type IV, 3 of 6 type IIb and 1 of 4 type IIa patients.", "contents": "Effects of oxandrolone on plasma lipoproteins in patients with type IIa, IIb and IV hyperlipoproteinemia: occurrence of hypo-high density lipoproteinemia. The effects of oxandrolone on plasma lipids and lipoprotein composition in patients with type IIa, IIb and IV hyperlipoproteinemia were investigated. Oxandrolone (4 mg/day, for 28 days) induced a significant reduction in plasma and VLDL triglyceride. Reciprocal elevation of LDL cholesterol was observed in 8 of 10 type IV patients and in 2 of 5 type IIb patients. In patients with type IV hyperlipoproteinemia, significant reduction of plasma apolipoproteinB and VLDL apolipoprotein B and inverse LDL apolipoprotein B increment was observed after treatment with oxandrolone. HDL cholesterol was decreased. Hypo-high density lipoproteinemia defined as HDL cholesterol concentration below 40 mg/100 ml occurred in 7 of 10 type IV, 3 of 6 type IIb and 1 of 4 type IIa patients."}
{"id": "PMID:231952", "title": "Dextran sulfate precipitable (light) plasma lipoproteins in genetically active and passive rats fed two types of diet.", "content": "Genetically active and passive female rats were fed a purified sucrose/fat diet or a stock diet from the age of 11 to 27 weeks. The age-related increase in plasma total cholesterol concentration was much more pronounced in active rats fed the purified diet than in active rats fed the stock diet. No significant alteration with age took place in the plasma cholesterol level of passive rats fed the stock or the purified diet. The increase in body weight was somewhat greater in active and passive rats fed the purified diet than in those fed stock diet. The lipoprotein distribution at the age of 27 weeks was estimated using both polyacrylamide gel electrophoresis and dextran sulfate/Ca++ precipitation. As compared with the stock diet, the purified diet effected a decrease in the relative amount of prebeta and beta lipoproteins in both active and passive rats. The major effect was, however, a pronounced increase in the relative amount of dextran sulfate precipitable \"light prealpha\" lipoproteins with no effect on \"heavy prealpha\" or alpha lipoprotein percentages. Alpha lipoprotein percentages were slightly higher in active than in passive rats. The results confirm our earlier observation that there might be a dissociation between the dietary effect on the plasma total cholesterol level and on the lipoprotein distribution. The data also suggest that the hyperlipemic sucrose/fat diet causes a shift from the prebeta and beta lipoproteins to the \"light prealpha\" fractions.", "contents": "Dextran sulfate precipitable (light) plasma lipoproteins in genetically active and passive rats fed two types of diet. Genetically active and passive female rats were fed a purified sucrose/fat diet or a stock diet from the age of 11 to 27 weeks. The age-related increase in plasma total cholesterol concentration was much more pronounced in active rats fed the purified diet than in active rats fed the stock diet. No significant alteration with age took place in the plasma cholesterol level of passive rats fed the stock or the purified diet. The increase in body weight was somewhat greater in active and passive rats fed the purified diet than in those fed stock diet. The lipoprotein distribution at the age of 27 weeks was estimated using both polyacrylamide gel electrophoresis and dextran sulfate/Ca++ precipitation. As compared with the stock diet, the purified diet effected a decrease in the relative amount of prebeta and beta lipoproteins in both active and passive rats. The major effect was, however, a pronounced increase in the relative amount of dextran sulfate precipitable \"light prealpha\" lipoproteins with no effect on \"heavy prealpha\" or alpha lipoprotein percentages. Alpha lipoprotein percentages were slightly higher in active than in passive rats. The results confirm our earlier observation that there might be a dissociation between the dietary effect on the plasma total cholesterol level and on the lipoprotein distribution. The data also suggest that the hyperlipemic sucrose/fat diet causes a shift from the prebeta and beta lipoproteins to the \"light prealpha\" fractions."}
{"id": "PMID:231953", "title": "Effect of intravenous injection of CDP-choline, S-adenosyl-methionine and citiolone in subjects with hyperlipemia.", "content": "The effect of some drugs (CDP-choline, S-adenosyl-methionine and acetyl-homocysteinethiolactone) stimulating a number of liver enzymatic activities was studied in hyperlipemic patients to explore the role of liver function in hyperlipidemia. Recently a close connection between liver impairment and hyperlipemia has been observed. Twenty-eight, 13 and 10 hyperlipemic subjects received i.v. doses respectively, of CDP-choline (300 mg), S-adenosyl-methionine (SAMe) (45 mg) and citiolone (300 mg) in 100 ml saline solution during a 30 minute period. Plasma lipid fractions were evaluated basally and at the end of the injection. CDP-choline caused a significant decrease in plasma total lipids (p less than 0.001), cholesterol (p less than 0.01) and triglycerides (p less than 0.01) as well as a slight increase in beta - LP (p less than 0.05). SAMe injection was followed by a significant fall in plasma total lipids (p less than 0.05), cholesterol (p less than 0.001) and beta - LP+pre-beta LP/alpha - LP ratio (p less than 0.05), while alpha -LP increased significantly (p less than 0.05). Citiolone caused only a decrease in plasma cholesterol values (p less than 0.001). The data suggest that the hypolipidemic effect of the three compounds is due to a common mode of action, i.e., the stimulation of hepatic phospholipid biosynthesis, though in a different way.", "contents": "Effect of intravenous injection of CDP-choline, S-adenosyl-methionine and citiolone in subjects with hyperlipemia. The effect of some drugs (CDP-choline, S-adenosyl-methionine and acetyl-homocysteinethiolactone) stimulating a number of liver enzymatic activities was studied in hyperlipemic patients to explore the role of liver function in hyperlipidemia. Recently a close connection between liver impairment and hyperlipemia has been observed. Twenty-eight, 13 and 10 hyperlipemic subjects received i.v. doses respectively, of CDP-choline (300 mg), S-adenosyl-methionine (SAMe) (45 mg) and citiolone (300 mg) in 100 ml saline solution during a 30 minute period. Plasma lipid fractions were evaluated basally and at the end of the injection. CDP-choline caused a significant decrease in plasma total lipids (p less than 0.001), cholesterol (p less than 0.01) and triglycerides (p less than 0.01) as well as a slight increase in beta - LP (p less than 0.05). SAMe injection was followed by a significant fall in plasma total lipids (p less than 0.05), cholesterol (p less than 0.001) and beta - LP+pre-beta LP/alpha - LP ratio (p less than 0.05), while alpha -LP increased significantly (p less than 0.05). Citiolone caused only a decrease in plasma cholesterol values (p less than 0.001). The data suggest that the hypolipidemic effect of the three compounds is due to a common mode of action, i.e., the stimulation of hepatic phospholipid biosynthesis, though in a different way."}
{"id": "PMID:231954", "title": "High density lipoprotein cholesterol and myocardial infarction or sudden coronary death: a prospective case-control study in middle-aged men of the Oslo study.", "content": "The high density lipoprotein (HDL) cholesterol concentrations of frozen specimen obtained in 1972-73 are reported from 93 men aged 40-49 years who later developed coronary heart disease (CHD), and for 186 controls. Mean HDL cholesterol of CHD-patients was 7.9% lower than that of controls matched for smoking habits and serum concentrations of triglycerides and total cholesterol (p 0.05 for 82 men who had myocardial infarction, n.s. difference for 11 with sudden coronary death), and 10.2% lower (p 0.05) than that of controls who were not matched for the parameters mentioned. The present prospective study confirms that HDL cholesterol is inversely associated with the risk of developing CHD in middle-aged men.", "contents": "High density lipoprotein cholesterol and myocardial infarction or sudden coronary death: a prospective case-control study in middle-aged men of the Oslo study. The high density lipoprotein (HDL) cholesterol concentrations of frozen specimen obtained in 1972-73 are reported from 93 men aged 40-49 years who later developed coronary heart disease (CHD), and for 186 controls. Mean HDL cholesterol of CHD-patients was 7.9% lower than that of controls matched for smoking habits and serum concentrations of triglycerides and total cholesterol (p 0.05 for 82 men who had myocardial infarction, n.s. difference for 11 with sudden coronary death), and 10.2% lower (p 0.05) than that of controls who were not matched for the parameters mentioned. The present prospective study confirms that HDL cholesterol is inversely associated with the risk of developing CHD in middle-aged men."}
{"id": "PMID:231966", "title": "5'-Nucleotidase: solubilization, radiochemical analysis, and electrophoresis.", "content": "5'-Nucleotidase (5'-NT, E.C. 3.1.3.5) of cultured human and rodent cells was rendered soluble using the zwitterionic detergent Zwittergent 314. Optimal activity of 5'-NT was obtained when sonicated cells were incubated in solutions containing 0.75% (w/v) Zwittergent. A method was developed for the determination of the activity of 5'-NT in which the unutilized substrate, [14C]-AMP, was precipitated with lanthanum chloride and the soluble [14C]-adenosine was measured by scintillation counting. 5'-NT isozymes were separated using agarose gel electrophoresis and isoelectric focusing in polyacrylamide gel. The zones of enzyme activity were established by precipitation of unutilized [14C]-AMP with LaCl3, removal of soluble [14C)-adenosine by washing gels in water, and autoradiography. The zones of 5'-NT appeared as clear zones on darkened X-ray film. When analyzed by agarose gel electrophoresis, fibroblasts derived from human skin and rat liver produced a single zone of 5'-NT activity. The 5'-NT isozyme of rat cells migrated faster than that of human cells and was easy to distinguish. The presence of detergent in the sample and in the gel enhanced enzymatic activity and improved the separation of the isozymes. Isoelectric focusing resolved 5'-NT of human fibroblasts into two molecular forms, one of which focused in the region of pH 6 and the other at pH5.", "contents": "5'-Nucleotidase: solubilization, radiochemical analysis, and electrophoresis. 5'-Nucleotidase (5'-NT, E.C. 3.1.3.5) of cultured human and rodent cells was rendered soluble using the zwitterionic detergent Zwittergent 314. Optimal activity of 5'-NT was obtained when sonicated cells were incubated in solutions containing 0.75% (w/v) Zwittergent. A method was developed for the determination of the activity of 5'-NT in which the unutilized substrate, [14C]-AMP, was precipitated with lanthanum chloride and the soluble [14C]-adenosine was measured by scintillation counting. 5'-NT isozymes were separated using agarose gel electrophoresis and isoelectric focusing in polyacrylamide gel. The zones of enzyme activity were established by precipitation of unutilized [14C]-AMP with LaCl3, removal of soluble [14C)-adenosine by washing gels in water, and autoradiography. The zones of 5'-NT appeared as clear zones on darkened X-ray film. When analyzed by agarose gel electrophoresis, fibroblasts derived from human skin and rat liver produced a single zone of 5'-NT activity. The 5'-NT isozyme of rat cells migrated faster than that of human cells and was easy to distinguish. The presence of detergent in the sample and in the gel enhanced enzymatic activity and improved the separation of the isozymes. Isoelectric focusing resolved 5'-NT of human fibroblasts into two molecular forms, one of which focused in the region of pH 6 and the other at pH5."}
{"id": "PMID:231967", "title": "Expression of galactose-1-p-uridyltransferase in Chinese hamster x human galactosemia somatic cell hybrids.", "content": "Lymphocytes from a patient with classic galactosemia (GALT deficiency) were hybridized with a Chinese hamster cell line.  Electrophoretic valuation of GALT in 31 independently derived interspecific hybrid clones failed to demonstrate expression of the human GALT gene even when human chromosome 9 was present. Possible mechanisms for this lack of expression are presented.", "contents": "Expression of galactose-1-p-uridyltransferase in Chinese hamster x human galactosemia somatic cell hybrids. Lymphocytes from a patient with classic galactosemia (GALT deficiency) were hybridized with a Chinese hamster cell line.  Electrophoretic valuation of GALT in 31 independently derived interspecific hybrid clones failed to demonstrate expression of the human GALT gene even when human chromosome 9 was present. Possible mechanisms for this lack of expression are presented."}
{"id": "PMID:231968", "title": "Effects of inhibitory ligands on the aerobic carbon monoxide complex of cytochrome c oxidase.", "content": "1. In the presence of both CO and O2, ox heart cytochrome c oxidase forms a 607 nm-peak intermediate distinct from both the cytochrome a2+a3 2+CO and the cytochrome a3+a3 2+CO ('mixed-valence') CO complexes. 2. This aerobic CO compound is stable towards ferricyanide addition, but decomposed on treatment with ferric cytochrome a2 ligands such as formate, cyanide and azide. 3. Addition of formate or cyanves rise to a complex with alpha-peak at 598 nm, not identical with any azide complex of the free enzyme, but possibly a cytochrome a3 2+NO complex produced by oxidative attack of partially reduced O2 on the azide. 4. The results support the idea that although the initial reaction of oxygen is with cytochrome a3 2+, the next step is not an oxidation of the ferrous cytochrome a3, but a transfer of O2 to a neighbouring group, such as Cu+, to give Cu2+O2- or similar complexes. 5. The aerobic CO complex is then identified as a3+a3 2+COCu2+O2-; a similar compound ('Compound C') is formed by photolysis of a3+a3 2+CO (the 'mixed-valence' CO complex) in the presence of oxygen at low temperatures.", "contents": "Effects of inhibitory ligands on the aerobic carbon monoxide complex of cytochrome c oxidase. 1. In the presence of both CO and O2, ox heart cytochrome c oxidase forms a 607 nm-peak intermediate distinct from both the cytochrome a2+a3 2+CO and the cytochrome a3+a3 2+CO ('mixed-valence') CO complexes. 2. This aerobic CO compound is stable towards ferricyanide addition, but decomposed on treatment with ferric cytochrome a2 ligands such as formate, cyanide and azide. 3. Addition of formate or cyanves rise to a complex with alpha-peak at 598 nm, not identical with any azide complex of the free enzyme, but possibly a cytochrome a3 2+NO complex produced by oxidative attack of partially reduced O2 on the azide. 4. The results support the idea that although the initial reaction of oxygen is with cytochrome a3 2+, the next step is not an oxidation of the ferrous cytochrome a3, but a transfer of O2 to a neighbouring group, such as Cu+, to give Cu2+O2- or similar complexes. 5. The aerobic CO complex is then identified as a3+a3 2+COCu2+O2-; a similar compound ('Compound C') is formed by photolysis of a3+a3 2+CO (the 'mixed-valence' CO complex) in the presence of oxygen at low temperatures."}
{"id": "PMID:231969", "title": "Partial purification and characterization of deoxyguanosine kinase from pig skin.", "content": "Deoxyguanosine kinase, which catalyses the phosphorylation of deoxyguanosine to form deoxyguanosine 5'-monophosphate, was purified 1024-fold from extracts to newborn-pig skin. This activity requires the presence of a bivalent cation and a nucleoside triphosphate, which functions as a phosphate donor, ATP being twice as effective as CTP or GTP and 4 times as effective as UTP. The enzyme appears to have a molecular weight of 58500 as determined by Sephadex-column chromatography. Optimal enzymic activity was observed at pH 8.0; however, the enzyme remained active over a broad pH range of 5.5-9.0. Several deoxyribonucleoside and ribonucleoside monophosphates and triphosphates were tested as effectors of catalytic activity. Effective inhibitors were dGMP [Ki(app.) = 7.6 x 10(-5) M] and dGTP [Ki(app.) = 2.1 x 10(-5) M]. Both of these inhibitors acted in a competitive manner. A Km(app.) of 3.2 x 10(-7) M was measured for deoxyguanosine and a Km(app.) of 3.3 mM was determined for MgATP. Of the four major deoxynucleosides tested, this catalytic activity appears to phosphorylate only deoxyguanosine; thus the enzyme is a specific deoxyguanosine kinase.", "contents": "Partial purification and characterization of deoxyguanosine kinase from pig skin. Deoxyguanosine kinase, which catalyses the phosphorylation of deoxyguanosine to form deoxyguanosine 5'-monophosphate, was purified 1024-fold from extracts to newborn-pig skin. This activity requires the presence of a bivalent cation and a nucleoside triphosphate, which functions as a phosphate donor, ATP being twice as effective as CTP or GTP and 4 times as effective as UTP. The enzyme appears to have a molecular weight of 58500 as determined by Sephadex-column chromatography. Optimal enzymic activity was observed at pH 8.0; however, the enzyme remained active over a broad pH range of 5.5-9.0. Several deoxyribonucleoside and ribonucleoside monophosphates and triphosphates were tested as effectors of catalytic activity. Effective inhibitors were dGMP [Ki(app.) = 7.6 x 10(-5) M] and dGTP [Ki(app.) = 2.1 x 10(-5) M]. Both of these inhibitors acted in a competitive manner. A Km(app.) of 3.2 x 10(-7) M was measured for deoxyguanosine and a Km(app.) of 3.3 mM was determined for MgATP. Of the four major deoxynucleosides tested, this catalytic activity appears to phosphorylate only deoxyguanosine; thus the enzyme is a specific deoxyguanosine kinase."}
{"id": "PMID:231970", "title": "Purification of pig synovial collagenase to high specific activity.", "content": "1. Pig synovium in tissue culture secretes a specific collagenase in a latent form. 2. The latent enzyme was concentrated by (NH4)2SO4 precipitation and activated with 4-aminophenylmercuric acetate, and the active enzyme was purified by chromatography on Ultrogel AcA44, DEAE-cellulose, heparin-Sepharose and a zinc-chelate medium to a specific activity of 53 400 units/mg. of protein. 3. The enzyme was shown to be essentially homogeneous by polyacrylamide-gel electrophoresis. 4. The purified collagenase digested collagen to give the characteristic three-quarter and one-quarter pieces.", "contents": "Purification of pig synovial collagenase to high specific activity. 1. Pig synovium in tissue culture secretes a specific collagenase in a latent form. 2. The latent enzyme was concentrated by (NH4)2SO4 precipitation and activated with 4-aminophenylmercuric acetate, and the active enzyme was purified by chromatography on Ultrogel AcA44, DEAE-cellulose, heparin-Sepharose and a zinc-chelate medium to a specific activity of 53 400 units/mg. of protein. 3. The enzyme was shown to be essentially homogeneous by polyacrylamide-gel electrophoresis. 4. The purified collagenase digested collagen to give the characteristic three-quarter and one-quarter pieces."}
{"id": "PMID:231971", "title": "Evidence for the occurrence of an ecto-(adenosine triphosphatase) in rat epididymal spermatozoa.", "content": "Intact spermatozoa from rat cauda epididymis possess a Mg2+-dependent ATPase activity that hydrolyses externally added [gamma-32P]ATP. The ATPase reaction was linear with time for approx. 6 min and there was no detectable uptake of ATP by these cells. The ATPase activity of the whole spermatozoa was not due to leakage of the intracellular enzymic activity, contamination of the broken cells or any possible cell damage during incubation and isolation of spermatozoa. The activity of the enzyme was strongly inhibited (approx. 85%) by p-chloromercuribenzenesulphonic acid (50 microM) or the diazonium salt of sulphanilic acid (50 microM), which are believed not to enter the cells, whereas ouabain (0.5 mM), NaF (10 mM), NaN3 (2.5 mM) and oligomycin (5 microM) had no appreciable effect on the activity of the spermatozoal APTase. There was little loss of ATPase activity from the cells when washed with 0.5 mM-EDTA and an iso-osmotic or hyperosmotic medium. These data are consistent with the view that the observed ATPase activity is located on the external surface of spermatozoa. The sperm ecto-ATPase activity is resistant to the action of proteinases (50 micrograms/ml), namely trypsin, chymotrypsin and Pronase. Studies with various unlabelled phosphate esters indicate that the sperm ecto-ATPase is not a non-specific phosphatase and it has high degree of substrate specificity for ATP.", "contents": "Evidence for the occurrence of an ecto-(adenosine triphosphatase) in rat epididymal spermatozoa. Intact spermatozoa from rat cauda epididymis possess a Mg2+-dependent ATPase activity that hydrolyses externally added [gamma-32P]ATP. The ATPase reaction was linear with time for approx. 6 min and there was no detectable uptake of ATP by these cells. The ATPase activity of the whole spermatozoa was not due to leakage of the intracellular enzymic activity, contamination of the broken cells or any possible cell damage during incubation and isolation of spermatozoa. The activity of the enzyme was strongly inhibited (approx. 85%) by p-chloromercuribenzenesulphonic acid (50 microM) or the diazonium salt of sulphanilic acid (50 microM), which are believed not to enter the cells, whereas ouabain (0.5 mM), NaF (10 mM), NaN3 (2.5 mM) and oligomycin (5 microM) had no appreciable effect on the activity of the spermatozoal APTase. There was little loss of ATPase activity from the cells when washed with 0.5 mM-EDTA and an iso-osmotic or hyperosmotic medium. These data are consistent with the view that the observed ATPase activity is located on the external surface of spermatozoa. The sperm ecto-ATPase activity is resistant to the action of proteinases (50 micrograms/ml), namely trypsin, chymotrypsin and Pronase. Studies with various unlabelled phosphate esters indicate that the sperm ecto-ATPase is not a non-specific phosphatase and it has high degree of substrate specificity for ATP."}
{"id": "PMID:231972", "title": "Characteristics of the rat liver microsomal enzyme system converting cholecalciferol into 25-hydroxycholecalciferol. Evidence for the participation of cytochrome p-450.", "content": "Properties of the rat hepatic cholecalciferol 25-hydroxylase have been studied. An assay system has been developed in which 25-hydroxycholecalciferol production is linear for at least 2h in both homogenates and microsomal fraction. Furthermore, the initial reaction velocity is linearly related to the amount of liver tissue or microsomal fraction. This enzyme system also metabolizes an analogue of cholecalciferol, namely dihydrotachysterol 3, into 25-hydroxydihydrotachysterol 3. The 25-hydroxylase is in the microsomal fraction and not in mitochondria. It has a Km of 44 nM for cholecalciferol and 360 nM for dihydrotachysterol 3. Its activity is not altered by dietary concentrations of calcium and phosphorus. Vitamin D-deficient rats have higher activities of the hepatic 25-hydroxylase than those receiving 25 ng of cholecalciferol daily. The 25-hydroxylase is inhibited by metyrapone. An atmosphere of CO/O2 (9:1, v/v) inhibits the reaction by 87%. This inhibition is partially reversed by white light. Additionally, cholecalciferol and 25-hydroxycholecalciferol competitively inhibit aminopyrine demethylase. These results support the idea that the cholecalciferol 25-hydroxylase is a cytochrome P-450-dependent mono-oxygenase.", "contents": "Characteristics of the rat liver microsomal enzyme system converting cholecalciferol into 25-hydroxycholecalciferol. Evidence for the participation of cytochrome p-450. Properties of the rat hepatic cholecalciferol 25-hydroxylase have been studied. An assay system has been developed in which 25-hydroxycholecalciferol production is linear for at least 2h in both homogenates and microsomal fraction. Furthermore, the initial reaction velocity is linearly related to the amount of liver tissue or microsomal fraction. This enzyme system also metabolizes an analogue of cholecalciferol, namely dihydrotachysterol 3, into 25-hydroxydihydrotachysterol 3. The 25-hydroxylase is in the microsomal fraction and not in mitochondria. It has a Km of 44 nM for cholecalciferol and 360 nM for dihydrotachysterol 3. Its activity is not altered by dietary concentrations of calcium and phosphorus. Vitamin D-deficient rats have higher activities of the hepatic 25-hydroxylase than those receiving 25 ng of cholecalciferol daily. The 25-hydroxylase is inhibited by metyrapone. An atmosphere of CO/O2 (9:1, v/v) inhibits the reaction by 87%. This inhibition is partially reversed by white light. Additionally, cholecalciferol and 25-hydroxycholecalciferol competitively inhibit aminopyrine demethylase. These results support the idea that the cholecalciferol 25-hydroxylase is a cytochrome P-450-dependent mono-oxygenase."}
{"id": "PMID:231973", "title": "The reaction of cytochrome oxidase with oxygen in the fission yeast Schizosaccharomyces pombe 972h-. Studies at subzero temperatures and measurement of apparent oxygen affinity.", "content": "1. Cytochrome alpha 3 in whole-cell suspensions of the fission yeast Schizosaccharomyces pombe reacted in the reduced form with CO to give a photodissociable CO complex with absorption maxima at 429, 543 and 591 nm in CO-liganded reduced-minus-reduced difference spectra. 2. Other CO-bound haemoproteins, cytochromes P-420 and P-450, were not photodissociated under the conditions employed. 3. Measurements of the rates of reassociation of CO with cytochrome alpha 3 after flash photolysis over the temperature range from -101 to -109 degrees C gave a value for Eact. of 28.6 kJ/mol. 4. Between -94 and -106 degrees C, O2 reacted with cytochrome oxidase in intact cells to give an oxygenated intermediate (compound A). 5. At -70 degrees C compound A was converted into a second spectrally distinct intermediate (compound B). 6. Electron transport, indicated by the oxidation of cytochromes alpha + alpha 3 and cytochrome c, did not occur until the temperature was raised to -50 degrees C. 7. At room temperature cytochfome oxidase was oxidized to 50% of its steady-state concentration by 0.35 microM-O2.", "contents": "The reaction of cytochrome oxidase with oxygen in the fission yeast Schizosaccharomyces pombe 972h-. Studies at subzero temperatures and measurement of apparent oxygen affinity. 1. Cytochrome alpha 3 in whole-cell suspensions of the fission yeast Schizosaccharomyces pombe reacted in the reduced form with CO to give a photodissociable CO complex with absorption maxima at 429, 543 and 591 nm in CO-liganded reduced-minus-reduced difference spectra. 2. Other CO-bound haemoproteins, cytochromes P-420 and P-450, were not photodissociated under the conditions employed. 3. Measurements of the rates of reassociation of CO with cytochrome alpha 3 after flash photolysis over the temperature range from -101 to -109 degrees C gave a value for Eact. of 28.6 kJ/mol. 4. Between -94 and -106 degrees C, O2 reacted with cytochrome oxidase in intact cells to give an oxygenated intermediate (compound A). 5. At -70 degrees C compound A was converted into a second spectrally distinct intermediate (compound B). 6. Electron transport, indicated by the oxidation of cytochromes alpha + alpha 3 and cytochrome c, did not occur until the temperature was raised to -50 degrees C. 7. At room temperature cytochfome oxidase was oxidized to 50% of its steady-state concentration by 0.35 microM-O2."}
{"id": "PMID:231974", "title": "Turnover of adenosine 3':5'-cyclic monophosphate in chicken erythrocytes.", "content": "Turnover of cyclic AMP was studied in intact chicken erythrocytes. Production of cyclic AMP was stimulated by adrenaline and then blocked by propranolol. The decline in the cyclic AMP concentration under these conditions is solely due to its intracellular degradation, whereas efflux of the nucleotide, although existing in these cells, does not contribute significantly to the change in its concentration. Intracellular degradation of cyclic AMP follows a first-order kinetics with a half-life of about 6 min. Similar half-lives were obtained at widely different adrenaline concentrations or when the ration of propranolol to adrenaline was varied by 25-fold. Theoretical equations were applied to calculate the rates of cyclic AMP synthesis and degradation in the intact cells under different experimental conditions. Maximal adrenaline concentrations raise the rate of cyclic AMP synthesis and its steady-state concentration by about 10-fold. The addition of caffeine causes a further 33% increase in intracellular concentration of the nucleotide, which is in good agreement with the theoretical increase computed from its slowed-down degradation.", "contents": "Turnover of adenosine 3':5'-cyclic monophosphate in chicken erythrocytes. Turnover of cyclic AMP was studied in intact chicken erythrocytes. Production of cyclic AMP was stimulated by adrenaline and then blocked by propranolol. The decline in the cyclic AMP concentration under these conditions is solely due to its intracellular degradation, whereas efflux of the nucleotide, although existing in these cells, does not contribute significantly to the change in its concentration. Intracellular degradation of cyclic AMP follows a first-order kinetics with a half-life of about 6 min. Similar half-lives were obtained at widely different adrenaline concentrations or when the ration of propranolol to adrenaline was varied by 25-fold. Theoretical equations were applied to calculate the rates of cyclic AMP synthesis and degradation in the intact cells under different experimental conditions. Maximal adrenaline concentrations raise the rate of cyclic AMP synthesis and its steady-state concentration by about 10-fold. The addition of caffeine causes a further 33% increase in intracellular concentration of the nucleotide, which is in good agreement with the theoretical increase computed from its slowed-down degradation."}
{"id": "PMID:231975", "title": "Macrophage-fibroblast interactions in collagenase production and cartilage degradation.", "content": "Rabbit bone-marrow macrophages and fibroblasts were cultured, independently or together, with pieces of 35S-labelled cartilage or at the surface of dried [14C]collagen gels. Each type of cell, cultivated alone, rapidly degraded the proteoglycan of cartilage, but only the fibroblasts degraded collagen. The co-culture of both types of cell had no consistent effect on the rate of proteoglycan degradation, but it stimulated the rate of collagen degradation. In parallel, the accumulation of collagenase in the culture fluid was enhanced but not that of neutral proteinase. Coinditioned media from macrophage cultures added to cultures of fibroblasts had the same effect as the living macrophages in stimulating the production of collagenase. Their action was itself enhanced when the macrophages had been activated by concanavalin A-stimulated spleen-cell factors. These data suggest that fibroblasts may act as effector cells in producing collagenase and degrading collagen in response to soluble factors released by macrophages under the control of lymphocyte factors.", "contents": "Macrophage-fibroblast interactions in collagenase production and cartilage degradation. Rabbit bone-marrow macrophages and fibroblasts were cultured, independently or together, with pieces of 35S-labelled cartilage or at the surface of dried [14C]collagen gels. Each type of cell, cultivated alone, rapidly degraded the proteoglycan of cartilage, but only the fibroblasts degraded collagen. The co-culture of both types of cell had no consistent effect on the rate of proteoglycan degradation, but it stimulated the rate of collagen degradation. In parallel, the accumulation of collagenase in the culture fluid was enhanced but not that of neutral proteinase. Coinditioned media from macrophage cultures added to cultures of fibroblasts had the same effect as the living macrophages in stimulating the production of collagenase. Their action was itself enhanced when the macrophages had been activated by concanavalin A-stimulated spleen-cell factors. These data suggest that fibroblasts may act as effector cells in producing collagenase and degrading collagen in response to soluble factors released by macrophages under the control of lymphocyte factors."}
{"id": "PMID:231978", "title": "Ultrastructural and virological aspects of Langat virus-induced SSPE in suckling hamsters.", "content": "The morphology of subacute sclerosing panencephalitis (SSPE) lesions in hamsters following i.p. inoculation of Langat virus was studied by light microscopy and electron microscopy. The lesions' temporal relationship to virus presence and antibody production was studied by immunofluorescence, virus isolation from brains and brain cell cultures, and by antibody assay of serum and spinal fluid. All 10-day-old hamsters infected with Langat virus developed SSPE lesions, most prominently in the cerebellum, without any overt signs. The lesions appeared 10 days after infection, progressed in severity until Day 21 and persisted unaltered at least 3 months. They consisted of neuronal degeneration, calcification, and intracellular lipid accumulation. Virus was isolated from Days 3 to 15 and disappeared on Day 21. Demonstration by cerebellar immunofluorescence of viral antigen was observed 10 days after inoculation. Antibody appeared in the serum on Day 6, rose to very high titres by Day 21, and thereafter declined. Cell-associated virus was not demonstrable in negative brain-cell cultures. These findings suggest that SSPE in hamsters, associated with Langat virus infection, is biologically different from measles SSPE. Purkinje-cell lipid accumulation and mineralization sparing mitochondria were manifestations of the response of neurons to cell injury at the threshold of irreversibility.", "contents": "Ultrastructural and virological aspects of Langat virus-induced SSPE in suckling hamsters. The morphology of subacute sclerosing panencephalitis (SSPE) lesions in hamsters following i.p. inoculation of Langat virus was studied by light microscopy and electron microscopy. The lesions' temporal relationship to virus presence and antibody production was studied by immunofluorescence, virus isolation from brains and brain cell cultures, and by antibody assay of serum and spinal fluid. All 10-day-old hamsters infected with Langat virus developed SSPE lesions, most prominently in the cerebellum, without any overt signs. The lesions appeared 10 days after infection, progressed in severity until Day 21 and persisted unaltered at least 3 months. They consisted of neuronal degeneration, calcification, and intracellular lipid accumulation. Virus was isolated from Days 3 to 15 and disappeared on Day 21. Demonstration by cerebellar immunofluorescence of viral antigen was observed 10 days after inoculation. Antibody appeared in the serum on Day 6, rose to very high titres by Day 21, and thereafter declined. Cell-associated virus was not demonstrable in negative brain-cell cultures. These findings suggest that SSPE in hamsters, associated with Langat virus infection, is biologically different from measles SSPE. Purkinje-cell lipid accumulation and mineralization sparing mitochondria were manifestations of the response of neurons to cell injury at the threshold of irreversibility."}
{"id": "PMID:231979", "title": "Allosteric oscillatory enzymes: influence of the number of protomers on metabolic periodicities.", "content": "The study of a concerted allosteric model for an enzyme activated by the reaction product shows that this system can generate sustained metabolic oscillations regardless of the number of protomers constituting the enzyme. The analysis extends the results previously obtained in a dimeric model for the phosphofructokinase reaction which produces glycolytic periodicities. When the substrate and product concentrations evolve on comparable time scales, the amplitude of oscillations significantly drops as the number of enzyme subunits evolves from 2 to 8. The width of the domain of substrate injection rates which produce oscillations and the periodic variation in enzyme activity also depend on the number of protomers and on the time scale structure of the system. Theoretical predictions are compared with the experiments on glycolytic oscillations in yeast and muscle, and with the structural characteristics of phosphofructokinase. The results are also discussed in relation with the mechanism of cyclic AMP oscillations in the slime mold Dictyostelium discoideum.", "contents": "Allosteric oscillatory enzymes: influence of the number of protomers on metabolic periodicities. The study of a concerted allosteric model for an enzyme activated by the reaction product shows that this system can generate sustained metabolic oscillations regardless of the number of protomers constituting the enzyme. The analysis extends the results previously obtained in a dimeric model for the phosphofructokinase reaction which produces glycolytic periodicities. When the substrate and product concentrations evolve on comparable time scales, the amplitude of oscillations significantly drops as the number of enzyme subunits evolves from 2 to 8. The width of the domain of substrate injection rates which produce oscillations and the periodic variation in enzyme activity also depend on the number of protomers and on the time scale structure of the system. Theoretical predictions are compared with the experiments on glycolytic oscillations in yeast and muscle, and with the structural characteristics of phosphofructokinase. The results are also discussed in relation with the mechanism of cyclic AMP oscillations in the slime mold Dictyostelium discoideum."}
{"id": "PMID:231980", "title": "The influence of adenosine on intermediary metabolism of isolated hepatocytes.", "content": "The effect of adenosine was tested on the energetic metabolism of fed rat liver cells after isolation. The cells were incubated in a buffered saline medium with glucose (5 mM) and adenosine (1 mM) for 30 minutes at 37 degrees C. This increased the concentration of the adenylic nucleotides ATP (+57 per cent, ADP (+39 per cent). Cyclic AMP was increased (+50 per cent) and the intracellular inorganic phosphate decreased (-22 per cent). These changes were accompaned by a decrease of glycogenolysis, glucose consumption and lactate production. Measurement of glycolytic intermediates showed decreased concentrations of fructose 1,6-bis-phosphate and 3-phosphoglycerate proportional to the increase in ATP concentration. The near-equilibrium of the glyceraldehyde 3-phosphate dehydrogenase-phosphoglycerate kinase system was not modified by adenosine. The decrease of the NAD+/NADH ratio along with the increase of the ATP/ADP X PO4 ratio explains the decrease of 3-phosphoglycerate. The decrease in glucose consumption can be explained by the cross over at the phosphofructokinase stage with the decrease of fructose 1,6-bisphosphate. The major part of adenosine was deaminated as indicated by an increase in the production of ammonia and urea. The effects of inosine, or adenosine along with an inhibitor of adenosine deaminase (pentostatin) suggest that adenosine acts on the glucose consumption through adenylic nucleotides. However the increase of the adenylic nucleotide level cannot totally explain the other metabolic changes: decrease of the NAD+/NADH cytoplasmic ratio, constancy of this ratio in mitochondria, decrease of gluconeogenesis from lactate. A direct action of adenosine can therefore be expected.", "contents": "The influence of adenosine on intermediary metabolism of isolated hepatocytes. The effect of adenosine was tested on the energetic metabolism of fed rat liver cells after isolation. The cells were incubated in a buffered saline medium with glucose (5 mM) and adenosine (1 mM) for 30 minutes at 37 degrees C. This increased the concentration of the adenylic nucleotides ATP (+57 per cent, ADP (+39 per cent). Cyclic AMP was increased (+50 per cent) and the intracellular inorganic phosphate decreased (-22 per cent). These changes were accompaned by a decrease of glycogenolysis, glucose consumption and lactate production. Measurement of glycolytic intermediates showed decreased concentrations of fructose 1,6-bis-phosphate and 3-phosphoglycerate proportional to the increase in ATP concentration. The near-equilibrium of the glyceraldehyde 3-phosphate dehydrogenase-phosphoglycerate kinase system was not modified by adenosine. The decrease of the NAD+/NADH ratio along with the increase of the ATP/ADP X PO4 ratio explains the decrease of 3-phosphoglycerate. The decrease in glucose consumption can be explained by the cross over at the phosphofructokinase stage with the decrease of fructose 1,6-bisphosphate. The major part of adenosine was deaminated as indicated by an increase in the production of ammonia and urea. The effects of inosine, or adenosine along with an inhibitor of adenosine deaminase (pentostatin) suggest that adenosine acts on the glucose consumption through adenylic nucleotides. However the increase of the adenylic nucleotide level cannot totally explain the other metabolic changes: decrease of the NAD+/NADH cytoplasmic ratio, constancy of this ratio in mitochondria, decrease of gluconeogenesis from lactate. A direct action of adenosine can therefore be expected."}
{"id": "PMID:231981", "title": "[Preparation and seric form of rabbit C reactive protein].", "content": "The preparation of rabbit C-reactive protein (CRP) involves a single step affinity chromatography. This preparation takes advantage of the calcium-dependent affinity of CRP for an agarose gel bearing 2-aminoethanol dihydrogen-phosphate as a ligand. A prior chromatography on agarose gel without the ligand allows the uptake of the serum amyloid P-component (SAP). The CRP prepared according to this method is able to form precipitating complexes in agarose with rabbit lipoproteins. The specificity of these interactions is studied. It is demonstrated that CRP-High Density Lipoproteins (HLD) association produces a second precipitation arc when the pure CRP is revealed by a specific antiserum in agarose. Moreover, CRP in the serum is shown to be in the bound form only, and the binding involves Low Density Lipoproteins (LDL) exclusively.", "contents": "[Preparation and seric form of rabbit C reactive protein]. The preparation of rabbit C-reactive protein (CRP) involves a single step affinity chromatography. This preparation takes advantage of the calcium-dependent affinity of CRP for an agarose gel bearing 2-aminoethanol dihydrogen-phosphate as a ligand. A prior chromatography on agarose gel without the ligand allows the uptake of the serum amyloid P-component (SAP). The CRP prepared according to this method is able to form precipitating complexes in agarose with rabbit lipoproteins. The specificity of these interactions is studied. It is demonstrated that CRP-High Density Lipoproteins (HLD) association produces a second precipitation arc when the pure CRP is revealed by a specific antiserum in agarose. Moreover, CRP in the serum is shown to be in the bound form only, and the binding involves Low Density Lipoproteins (LDL) exclusively."}
{"id": "PMID:231982", "title": "Conformational effects of coenzyme binding to porcine lactic dehydrogenase.", "content": "Changes induced on addition of the coenzyme, NADH or NAD+, to porcine lactic dehydrogenase isoenzymes H4 and M4 have been studied by hydrodynamic and spectroscopic methods. As shown by ultracentrifugal analysis, the native subunit structure remains unchanged on holoenzyme formation; an approximately 5% increase of the sedimentation coefficient, parallelled by a slight decrease of the partial specific volume (less than 1%) indicate a significant change in the native tertiary and/or quaternary structure of the enzymes, corroborating earlier calorimetric data (Hinz and Jaenicke, 1975). The binding constant for the enzyme from skeletal muscle (M4) and NADH are found to be in agreement with KD-values obtained from equilibrium dialysis, as well as spectroscopic and thermal titration experiments (8 muM). Far UV circular dichroism measurements do not show significant changes on ligand binding, indicating unchanged helicity or compensatory conformational effects. In the near UV, ligand binding is reflected by an extrinsic Cotton effect around 340 nm; in the range of aromatic absorption no changes are detectable. The experimental results suggest that there are gross structural changes on coenzyme binding to lactic dehydrogenase which do not affect the intrinsic spectral properties normally applied to analyze transconformation reactions in protein molecules.", "contents": "Conformational effects of coenzyme binding to porcine lactic dehydrogenase. Changes induced on addition of the coenzyme, NADH or NAD+, to porcine lactic dehydrogenase isoenzymes H4 and M4 have been studied by hydrodynamic and spectroscopic methods. As shown by ultracentrifugal analysis, the native subunit structure remains unchanged on holoenzyme formation; an approximately 5% increase of the sedimentation coefficient, parallelled by a slight decrease of the partial specific volume (less than 1%) indicate a significant change in the native tertiary and/or quaternary structure of the enzymes, corroborating earlier calorimetric data (Hinz and Jaenicke, 1975). The binding constant for the enzyme from skeletal muscle (M4) and NADH are found to be in agreement with KD-values obtained from equilibrium dialysis, as well as spectroscopic and thermal titration experiments (8 muM). Far UV circular dichroism measurements do not show significant changes on ligand binding, indicating unchanged helicity or compensatory conformational effects. In the near UV, ligand binding is reflected by an extrinsic Cotton effect around 340 nm; in the range of aromatic absorption no changes are detectable. The experimental results suggest that there are gross structural changes on coenzyme binding to lactic dehydrogenase which do not affect the intrinsic spectral properties normally applied to analyze transconformation reactions in protein molecules."}
{"id": "PMID:231983", "title": "[Prostaglandins, cyclic nucleotides and heart adaptation to acute and chronic pressure overload].", "content": "The content of prostaglandins (PGs) and cyclic nucleotides was determined in the rat heart at different time following coarctation of the abdominal aorta. The animals were divided into three groups according to the rate and degree of hypertrophy. The rats with the best adaptability (the highest level of hypertrophy) showed the highest myocardial PG content. An increase in myocardial weight in response to the overload correlated with an enhancement in PGE/PGF2 ratio. The relationship between the myocardial levels of PGs and cyclic nucleotides during the period of adaptation was also observed. Prostaglandins are suggested to play an important role in the heart adaptation to pressure overloads.", "contents": "[Prostaglandins, cyclic nucleotides and heart adaptation to acute and chronic pressure overload]. The content of prostaglandins (PGs) and cyclic nucleotides was determined in the rat heart at different time following coarctation of the abdominal aorta. The animals were divided into three groups according to the rate and degree of hypertrophy. The rats with the best adaptability (the highest level of hypertrophy) showed the highest myocardial PG content. An increase in myocardial weight in response to the overload correlated with an enhancement in PGE/PGF2 ratio. The relationship between the myocardial levels of PGs and cyclic nucleotides during the period of adaptation was also observed. Prostaglandins are suggested to play an important role in the heart adaptation to pressure overloads."}
{"id": "PMID:231984", "title": "[Differences in the structure of adrenalin and ACTH receptors in adipose cells of rats].", "content": "The treatment of adipose tissue of the rat epidiymis with trypsin decreased the lipolytic action of ACTH by 95%, and the lipolytic action of adrenalin by 50%. Supplementation of the incubation sample with lysolecithin suspension led to a complete loss of the tissue sensitivity to ACTH and a 40% decrease in the sensitivity to adrenalin. A conclusion is made about a different structure of adrenalin and ACTH-receptors in the plasma membrane of adipose cells.", "contents": "[Differences in the structure of adrenalin and ACTH receptors in adipose cells of rats]. The treatment of adipose tissue of the rat epidiymis with trypsin decreased the lipolytic action of ACTH by 95%, and the lipolytic action of adrenalin by 50%. Supplementation of the incubation sample with lysolecithin suspension led to a complete loss of the tissue sensitivity to ACTH and a 40% decrease in the sensitivity to adrenalin. A conclusion is made about a different structure of adrenalin and ACTH-receptors in the plasma membrane of adipose cells."}
{"id": "PMID:231985", "title": "[Circadian rhythm of changes in phospholipids and activity of non-specific phosphomonoesterases in rat liver].", "content": "The circadian rhythm of the content of total and individual phospholipids and the activity of alkaline and acid phosphatases was revealed in the liver of 130 white rats by the biochemical and histochemical methods. The concentration of phospholipids and enzymatic activity rise during the day time (9 a.m. - 15 p.m.). The results obtained suggest a good agreement between the structural and metabolic features of the liver during its maximal functional activity.", "contents": "[Circadian rhythm of changes in phospholipids and activity of non-specific phosphomonoesterases in rat liver]. The circadian rhythm of the content of total and individual phospholipids and the activity of alkaline and acid phosphatases was revealed in the liver of 130 white rats by the biochemical and histochemical methods. The concentration of phospholipids and enzymatic activity rise during the day time (9 a.m. - 15 p.m.). The results obtained suggest a good agreement between the structural and metabolic features of the liver during its maximal functional activity."}
{"id": "PMID:231992", "title": "The cyclic adenosine monophosphate phosphodiesterases of myoblasts, fibroblasts, and their somatic cell hybrids.", "content": "Three forms of cAMP phosphodiesterases are found in mouse L cells (fibroblasts) and rat skeletal myoblasts. The myoblast enzymes can be resolved by chromatography on DEAE-cellulose and the fibroblast enzymes by chromatography on DEAE-Biogel. The myoblast enzymes are \"high affinity\" cAMP specific forms and have different molecular weights, while all L-cell enzymes have an apparent molecular weight of 450,000. Only one of the L-cell enzymes is able to hydrolyze both cyclic guanosine monophosphate (cGMP) and cAMP. Hydrolysis of the latter is stimulated by micromolar amounts of cGMP. The myoblast x L cell hybrids possess at least five phosphodiesterases, three of which can be identified as being of myoblast or fibroblast origin. One of the fibroblast enzymes appears to be modified in hybrids. The entire phosphodiesterase regulatory system of the myoblasts is active in the hybrids.", "contents": "The cyclic adenosine monophosphate phosphodiesterases of myoblasts, fibroblasts, and their somatic cell hybrids. Three forms of cAMP phosphodiesterases are found in mouse L cells (fibroblasts) and rat skeletal myoblasts. The myoblast enzymes can be resolved by chromatography on DEAE-cellulose and the fibroblast enzymes by chromatography on DEAE-Biogel. The myoblast enzymes are \"high affinity\" cAMP specific forms and have different molecular weights, while all L-cell enzymes have an apparent molecular weight of 450,000. Only one of the L-cell enzymes is able to hydrolyze both cyclic guanosine monophosphate (cGMP) and cAMP. Hydrolysis of the latter is stimulated by micromolar amounts of cGMP. The myoblast x L cell hybrids possess at least five phosphodiesterases, three of which can be identified as being of myoblast or fibroblast origin. One of the fibroblast enzymes appears to be modified in hybrids. The entire phosphodiesterase regulatory system of the myoblasts is active in the hybrids."}
{"id": "PMID:231993", "title": "Enzymatic degradation and partial biosynthetic reconstitution of microsomal and mitochondrial membranes.", "content": "Guinea pig liver microsomal and mitochondrial membranes were degraded with phospholipase C and D followed by partial biosynthetic reconstitution. Activities of phosphatidylinositol synthetase in microsomal membranes and NADPH-cytochrome c reductase were almost completely lost after phospholipase C and D treatment; almost complete restoration of the original activity was achieved after biosynthesis of phosphatidylcholine in degraded microsomes, but was not reparable after biosynthesis of cytidinediphosphodiglycerides (CDP-diglycerides). The mitochondrial biosynthesis of polyglycerophosphatides was completely retained after degradation of these membranes with phospholipase C, but after similar treatment with phospholipase D, only about one-quarter of the original activity remained, the relative composition of polyglycerophosphatides being significantly different. The activity of NADPH-cytochrome c reductase of microsomes represented about 76% of the original activity after phospholipase C treatment, but only approximately 1% after treatment with phospholipase D. Although this activity could not be restored with CDP-diglyceride synthesis, it was restored to about 75% of the original activity after the biosynthesis of phosphatidylcholine in these fragments. These and additional experimental findings are discussed in terms of the relation between structural organization of lipids and proteins and enzymatic activities of membrane-bound phospholipid-synthesizing enzymes in microsomal and mitochondrial membranes isolated from guinea pig liver.", "contents": "Enzymatic degradation and partial biosynthetic reconstitution of microsomal and mitochondrial membranes. Guinea pig liver microsomal and mitochondrial membranes were degraded with phospholipase C and D followed by partial biosynthetic reconstitution. Activities of phosphatidylinositol synthetase in microsomal membranes and NADPH-cytochrome c reductase were almost completely lost after phospholipase C and D treatment; almost complete restoration of the original activity was achieved after biosynthesis of phosphatidylcholine in degraded microsomes, but was not reparable after biosynthesis of cytidinediphosphodiglycerides (CDP-diglycerides). The mitochondrial biosynthesis of polyglycerophosphatides was completely retained after degradation of these membranes with phospholipase C, but after similar treatment with phospholipase D, only about one-quarter of the original activity remained, the relative composition of polyglycerophosphatides being significantly different. The activity of NADPH-cytochrome c reductase of microsomes represented about 76% of the original activity after phospholipase C treatment, but only approximately 1% after treatment with phospholipase D. Although this activity could not be restored with CDP-diglyceride synthesis, it was restored to about 75% of the original activity after the biosynthesis of phosphatidylcholine in these fragments. These and additional experimental findings are discussed in terms of the relation between structural organization of lipids and proteins and enzymatic activities of membrane-bound phospholipid-synthesizing enzymes in microsomal and mitochondrial membranes isolated from guinea pig liver."}
{"id": "PMID:231994", "title": "Changes induced by cold adaptation in the brown adipose tissue from several species of rodents, with special reference to the mitochondrial components.", "content": "(1) The effects of cold adaptation upon the brown adipose tissue have been studied in rats, hamsters, mice, and guinea pigs. (2) Striking effects were found for total tissue as well as at the mitochondrial level, e.g., increases in protein and phospholipid contents, changes in phospholipid fatty acid composition (a decrease in the percentage of palmitic and palmitoleic acids and an increase in stearic and linoleic acids), and a change in the mitochondrial polypeptide composition (a marked increase in a 32000 molecular weight polypeptide, except for hamsters). (3) In situations where animals exhibit a greatly enhanced capacity for nonshivering thermogenesis (cold adaptation for rats, mice, and guinea pigs, birth for guinea pigs, and hibernation ability for hamsters, dormice, and garden dormice), brown fat mitochondria are characterized by the occurrence of large amounts of the 32000 molecular weight polypeptide characteristic of these mitochondria.", "contents": "Changes induced by cold adaptation in the brown adipose tissue from several species of rodents, with special reference to the mitochondrial components. (1) The effects of cold adaptation upon the brown adipose tissue have been studied in rats, hamsters, mice, and guinea pigs. (2) Striking effects were found for total tissue as well as at the mitochondrial level, e.g., increases in protein and phospholipid contents, changes in phospholipid fatty acid composition (a decrease in the percentage of palmitic and palmitoleic acids and an increase in stearic and linoleic acids), and a change in the mitochondrial polypeptide composition (a marked increase in a 32000 molecular weight polypeptide, except for hamsters). (3) In situations where animals exhibit a greatly enhanced capacity for nonshivering thermogenesis (cold adaptation for rats, mice, and guinea pigs, birth for guinea pigs, and hibernation ability for hamsters, dormice, and garden dormice), brown fat mitochondria are characterized by the occurrence of large amounts of the 32000 molecular weight polypeptide characteristic of these mitochondria."}
{"id": "PMID:231995", "title": "In vivo preparation of [32P]cAMP and thin-layer chromatography of cAMP-related compounds.", "content": "A simple and rapid method for preparing [32P]adenosine 3'5'-cyclic monophosphate (cAMP) is described. A culture of an Escherichia coli mutant which excretes cAMP about 150 times faster than does a wild-type strain was incubated overnight with [32P]orthophosphate of high specific activity (e.g., 4000 Ci/mol (1 Ci = 37 GBq). The [32P]cAMP which accumulated extracellularly was then purified to 99.9% radiochemical purity in less than 4 h by adsorption to charcoal and alumina column chromatography. A two-dimensional chromatography system using a PEI-cellulose plate is also described which should prove useful for studying cAMP metabolism with 32P- or 3H-labeled cAMP or ATP.", "contents": "In vivo preparation of [32P]cAMP and thin-layer chromatography of cAMP-related compounds. A simple and rapid method for preparing [32P]adenosine 3'5'-cyclic monophosphate (cAMP) is described. A culture of an Escherichia coli mutant which excretes cAMP about 150 times faster than does a wild-type strain was incubated overnight with [32P]orthophosphate of high specific activity (e.g., 4000 Ci/mol (1 Ci = 37 GBq). The [32P]cAMP which accumulated extracellularly was then purified to 99.9% radiochemical purity in less than 4 h by adsorption to charcoal and alumina column chromatography. A two-dimensional chromatography system using a PEI-cellulose plate is also described which should prove useful for studying cAMP metabolism with 32P- or 3H-labeled cAMP or ATP."}
{"id": "PMID:231996", "title": "The properties of purified low molecular weight phosphoprotein phosphatase from rabbit heart.", "content": "A simplified procedure for the purification of low molecular weight phosphoprotein phosphatase acting on muscle phosphorylase a has been described from rabbit heart. The enzyme was purified to homogeneity by acid precipitation, ethanol treatment, and chromatography on Sephadex G-75 and Sepharose-histone. The purified enzyme showed a single band when examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis; the molecular weight calculated by this method was 34 000. The S20, W value and Stokes radius for the enzyme was 3.35 and 24.0 A(1 A = 0.1 nm), respectively. Using these two values, a molecular weight of 35 000 was calculated. Purified enzyme showed a wide substrate specificity and catalyzed the dephosphorylation of phosphorylase a, glycogen synthase D, phosphorylated histone, and phosphorylated casein. Kinetic studies revealed the lowest Km with glycogen synthase D and maximum Vmax for the reaction with phosphorylase a.", "contents": "The properties of purified low molecular weight phosphoprotein phosphatase from rabbit heart. A simplified procedure for the purification of low molecular weight phosphoprotein phosphatase acting on muscle phosphorylase a has been described from rabbit heart. The enzyme was purified to homogeneity by acid precipitation, ethanol treatment, and chromatography on Sephadex G-75 and Sepharose-histone. The purified enzyme showed a single band when examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis; the molecular weight calculated by this method was 34 000. The S20, W value and Stokes radius for the enzyme was 3.35 and 24.0 A(1 A = 0.1 nm), respectively. Using these two values, a molecular weight of 35 000 was calculated. Purified enzyme showed a wide substrate specificity and catalyzed the dephosphorylation of phosphorylase a, glycogen synthase D, phosphorylated histone, and phosphorylated casein. Kinetic studies revealed the lowest Km with glycogen synthase D and maximum Vmax for the reaction with phosphorylase a."}
{"id": "PMID:231997", "title": "Components and mechanism of action of ATP-driven proton pumps.", "content": "We have studied the composition of ATP-driven proton pumps from bovine heart mitochondria and have reconstituted the oligomycin-sensitive ATPase complex from its individual components. The complex contains 9 to 10 subunits of which 5 are assembled in the soluble F1 protein, 2 are required for the attachment of F1 to the membrane and 2 form the proton channel within the membrane. With the help of information obtained from studies of the chloroplast and the bacterial proton pumps, we can tentatively assign a function to each of the subunits of the pump. The position of F1 outside of the membrane seen in electron micrographs of negatively stained preparations, does not appear to be an artifact. Evidence from immunological studies, chemical derivatizations as well as further electron microscopy (positive staining and freeze-etching), support this statement. We describe in this paper a 28 000-dalton polypeptide which has been isolated from the mitochondria membrane and is required for the reconstitution of oligomycin-sensitive ATPase and 32Pi-ATP exchange activity. We propose a mechanism of action of the proton pump in which the key energy-yielding reaction is the binding of Mg2+ to the protein. The function of the proton gradient is to displace Mg2+ from this site to permit cyclic repetition of the binding process. Essential for this scheme is the cyclic opening and closing of the proton channel. We have outlined our present approaches to test this hypothesis.", "contents": "Components and mechanism of action of ATP-driven proton pumps. We have studied the composition of ATP-driven proton pumps from bovine heart mitochondria and have reconstituted the oligomycin-sensitive ATPase complex from its individual components. The complex contains 9 to 10 subunits of which 5 are assembled in the soluble F1 protein, 2 are required for the attachment of F1 to the membrane and 2 form the proton channel within the membrane. With the help of information obtained from studies of the chloroplast and the bacterial proton pumps, we can tentatively assign a function to each of the subunits of the pump. The position of F1 outside of the membrane seen in electron micrographs of negatively stained preparations, does not appear to be an artifact. Evidence from immunological studies, chemical derivatizations as well as further electron microscopy (positive staining and freeze-etching), support this statement. We describe in this paper a 28 000-dalton polypeptide which has been isolated from the mitochondria membrane and is required for the reconstitution of oligomycin-sensitive ATPase and 32Pi-ATP exchange activity. We propose a mechanism of action of the proton pump in which the key energy-yielding reaction is the binding of Mg2+ to the protein. The function of the proton gradient is to displace Mg2+ from this site to permit cyclic repetition of the binding process. Essential for this scheme is the cyclic opening and closing of the proton channel. We have outlined our present approaches to test this hypothesis."}
{"id": "PMID:231998", "title": "Selective spin-labeling of the ribosomal proteins of 70S ribosomes from Escherichia coli.", "content": "We have used a series of N-(1-oxyl-2,2,5,5-tetramethyl-3-pyrrolidinyl) maleimide spin labels of different length to label, covalently and selectively, the most reactive sulfhydryl groups of 70S ribosomal proteins of Escherichia coli. Under short periods of labeling (1--2 min), less than two spin labels per ribosome are incorporated and were shown to be distributed mainly on five ribosomal proteins in the following order: S18 greater than S21, L27 greater than S17, and S12. With a long period of labeling (3 h) up to 13 spin labels are attached to the ribosome, and protein S1 is the most labeled. The shape of the electron paramagnetic resonance (epr) signal shows two components with a predominance for the strongly immobilized orientation, and the percentage of these components in each spectra has been evaluated. When the distance between the nitroxide group and the maleimide-attaching group exceeds 6 A (1 A = 0.1 nm) the strongly immobilized orientation disappears. The effect of magnesium ions on these selectively spinlabeled ribosomes shows that the dissociation into subunits does not affect the epr signal, but more spin labels are incorporated into the subunits if labeling is performed under conditions of dissociation.", "contents": "Selective spin-labeling of the ribosomal proteins of 70S ribosomes from Escherichia coli. We have used a series of N-(1-oxyl-2,2,5,5-tetramethyl-3-pyrrolidinyl) maleimide spin labels of different length to label, covalently and selectively, the most reactive sulfhydryl groups of 70S ribosomal proteins of Escherichia coli. Under short periods of labeling (1--2 min), less than two spin labels per ribosome are incorporated and were shown to be distributed mainly on five ribosomal proteins in the following order: S18 greater than S21, L27 greater than S17, and S12. With a long period of labeling (3 h) up to 13 spin labels are attached to the ribosome, and protein S1 is the most labeled. The shape of the electron paramagnetic resonance (epr) signal shows two components with a predominance for the strongly immobilized orientation, and the percentage of these components in each spectra has been evaluated. When the distance between the nitroxide group and the maleimide-attaching group exceeds 6 A (1 A = 0.1 nm) the strongly immobilized orientation disappears. The effect of magnesium ions on these selectively spinlabeled ribosomes shows that the dissociation into subunits does not affect the epr signal, but more spin labels are incorporated into the subunits if labeling is performed under conditions of dissociation."}
{"id": "PMID:231999", "title": "Inhibition of rat and human adipocyte adenylate cyclase in the antilipolytic action of insulin, clofibrate, and nicotinic acid.", "content": "Clofibrate (Atromid-S), nicotinic acid, and insulin are known to be potent hypolipidemic and antilipolytic agents. The present study was undertaken to define the mechanism of action of this latter effect on isolated rat and human fat cells. Sodium clofibrate (0.42 mM), nicotinic acid (0.42 mM), and insulin (100 microU/mL) were shown to inhibit norepinephrine-stimulated lipolysis in rat and human adipose cells and this inhibition was associated with a reduction in intracellular 3',5'-cyclic AMP levels. A similar cyclic AMP lowering effect was demonstrated with insulin in the presence of procaine-HCL, which uncouples the adenylate cyclase system from lipolysis. This insulin effect was attributed to inhibition of adenylate cyclase. A direct and significant inhibition of adenylate cyclase in membrane fractions obtained from isolated human adipocytes was demonstrated for all three antilipolytic agents. The common membrane site of action of these agents whereby adenylate cyclase activity is depressed, thus decreasing cyclic AMP production and free fatty acid (FFA) mobilization from adipose stores, implies a central role for the adenylate cyclase system. These findings are consistent with the view that the hypotriglyceridemic effects of clofibrate, nicotinic acid, and insulin may be partly explained by deprivation of FFA substrate for hepatic very low density lipoprotein synthesis.", "contents": "Inhibition of rat and human adipocyte adenylate cyclase in the antilipolytic action of insulin, clofibrate, and nicotinic acid. Clofibrate (Atromid-S), nicotinic acid, and insulin are known to be potent hypolipidemic and antilipolytic agents. The present study was undertaken to define the mechanism of action of this latter effect on isolated rat and human fat cells. Sodium clofibrate (0.42 mM), nicotinic acid (0.42 mM), and insulin (100 microU/mL) were shown to inhibit norepinephrine-stimulated lipolysis in rat and human adipose cells and this inhibition was associated with a reduction in intracellular 3',5'-cyclic AMP levels. A similar cyclic AMP lowering effect was demonstrated with insulin in the presence of procaine-HCL, which uncouples the adenylate cyclase system from lipolysis. This insulin effect was attributed to inhibition of adenylate cyclase. A direct and significant inhibition of adenylate cyclase in membrane fractions obtained from isolated human adipocytes was demonstrated for all three antilipolytic agents. The common membrane site of action of these agents whereby adenylate cyclase activity is depressed, thus decreasing cyclic AMP production and free fatty acid (FFA) mobilization from adipose stores, implies a central role for the adenylate cyclase system. These findings are consistent with the view that the hypotriglyceridemic effects of clofibrate, nicotinic acid, and insulin may be partly explained by deprivation of FFA substrate for hepatic very low density lipoprotein synthesis."}
{"id": "PMID:232000", "title": "Effect of carbon sources on the rates of cyclic AMP synthesis, excretion, and degradation, and the ability to produce beta-galactosidase in Escherichia coli.", "content": "We have determined the rates of adenosine 3',5'-cyclic monophosphate (cAMP) synthesis, excretion, and degradation, and the cAMP pool size in Escherichia coli grown on various carbon sources. We have found that the cAMP pool size increases in approximate proportion to increases in the cAMP synthetic rate. Although the combined rate of excretion and degradation of cAMP is in approximate proportion to the cAMP pool size, no such regular relationship is seen between the cAMP pool size and either the excretion rate or the degradation rate. Using a method which we have developed for determining the cellular efficiency of enzyme production (termed 'cellular' rate), we have reexamined the relationship between cAMP pool size and the rate of beta-galactosidase production. Although there exists an overall trend of increasing rate of beta-galactosidase production with increasing cAMP pool size, large variations in the rates of beta-galactosidase production are seen even under culture conditions which yield similar cAMP pool sizes. This suggests that the intracellular level of cAMP cannot be the unique regulator of beta-galactosidase production.", "contents": "Effect of carbon sources on the rates of cyclic AMP synthesis, excretion, and degradation, and the ability to produce beta-galactosidase in Escherichia coli. We have determined the rates of adenosine 3',5'-cyclic monophosphate (cAMP) synthesis, excretion, and degradation, and the cAMP pool size in Escherichia coli grown on various carbon sources. We have found that the cAMP pool size increases in approximate proportion to increases in the cAMP synthetic rate. Although the combined rate of excretion and degradation of cAMP is in approximate proportion to the cAMP pool size, no such regular relationship is seen between the cAMP pool size and either the excretion rate or the degradation rate. Using a method which we have developed for determining the cellular efficiency of enzyme production (termed 'cellular' rate), we have reexamined the relationship between cAMP pool size and the rate of beta-galactosidase production. Although there exists an overall trend of increasing rate of beta-galactosidase production with increasing cAMP pool size, large variations in the rates of beta-galactosidase production are seen even under culture conditions which yield similar cAMP pool sizes. This suggests that the intracellular level of cAMP cannot be the unique regulator of beta-galactosidase production."}
{"id": "PMID:232001", "title": "Horseradish peroxidase. XXXIV. Oxidation of compound II to I by periodate and inorganic anion radicals.", "content": "The one-electron oxidation of horseradish peroxidase compound II to compound I by sodium periodate was observed. The bimolecular rate constant for the NaIO4--compound II interaction is equal to 9.5 +/- 1 x 10(-3) M-1s-1 at room temperature. Irradiation, using ultraviolet light, of the solution containing compound II and persulfate in the presence of bicarbonate, chloride, or bromide, leads ot the fast accumulation of compound I due to the oxidative action of SO4, CO3, Cl2, and Br2 anion radicals, which are products of the photolysis.", "contents": "Horseradish peroxidase. XXXIV. Oxidation of compound II to I by periodate and inorganic anion radicals. The one-electron oxidation of horseradish peroxidase compound II to compound I by sodium periodate was observed. The bimolecular rate constant for the NaIO4--compound II interaction is equal to 9.5 +/- 1 x 10(-3) M-1s-1 at room temperature. Irradiation, using ultraviolet light, of the solution containing compound II and persulfate in the presence of bicarbonate, chloride, or bromide, leads ot the fast accumulation of compound I due to the oxidative action of SO4, CO3, Cl2, and Br2 anion radicals, which are products of the photolysis."}
{"id": "PMID:232002", "title": "Polioviruses and other enteroviruses in urban sewage from Laval (Canada): presence of non-vaccinal strains of poliovirus.", "content": "During a 13-month period (August 1, 1977-August 31, 1978) 55 samples of 2-4 L of raw sewage from an urban residential area were collected and studied for the presence of human enteroviruses. Viruses were recovered from 47 (90.5%) of the samples. Of the 201 viral isolates propagated, 180 (89.5%) were identified by the serum neutralization test as poliovirus types 1,2, or 3; 16 (8%) were identified as coxsackie B viruses; and 5 (2.5%) could not be identified by the methods used. While all polioviruses, types 2 and 3 isolates, were vaccine-like (rct-/d-) or intermediate strains, 14 poliovires, type 1 out of 55 selected isolates, were found to be non-vaccine-like (rct+/d+), 8 were rct-/d-), and 33 were intermediate strains. Out of nine samples submitted to the serodifferentiation (McBride) test, six poliovires, type 1 rct+/d+ and three rct+/d-, were related to wild strains.", "contents": "Polioviruses and other enteroviruses in urban sewage from Laval (Canada): presence of non-vaccinal strains of poliovirus. During a 13-month period (August 1, 1977-August 31, 1978) 55 samples of 2-4 L of raw sewage from an urban residential area were collected and studied for the presence of human enteroviruses. Viruses were recovered from 47 (90.5%) of the samples. Of the 201 viral isolates propagated, 180 (89.5%) were identified by the serum neutralization test as poliovirus types 1,2, or 3; 16 (8%) were identified as coxsackie B viruses; and 5 (2.5%) could not be identified by the methods used. While all polioviruses, types 2 and 3 isolates, were vaccine-like (rct-/d-) or intermediate strains, 14 poliovires, type 1 out of 55 selected isolates, were found to be non-vaccine-like (rct+/d+), 8 were rct-/d-), and 33 were intermediate strains. Out of nine samples submitted to the serodifferentiation (McBride) test, six poliovires, type 1 rct+/d+ and three rct+/d-, were related to wild strains."}
{"id": "PMID:232003", "title": "Effect of divalent cations on the inhibition of alkylsulfatase induction and the generation of ATP in Pseudomonas aeruginosa after exposure to exogenous uridine 5'-triphosphate.", "content": "In the absence of added Mg2+, alkylsulfatase induction in resting cells of Pseudomonas aeruginosa was inhibited 17% by exogenous 0.05 mM UTP. Under these conditions, the cells converted UTP to ATP and rapid degradation of these nucleotides did not occur. In the presence of 0.73 mM Mg2+, 0.05 mM UTP repressed the synthesis of the enzyme by 71%. Under these conditions, the cells rapidly degraded both ATP derived from UTP as well as residual UTP. In the presence of Mg2+ and 0.1 mM UTP, full repression of alkylsulfatase formation occurred whereas Mg2+-depleted cell suspensions were still capable of synthesizing 47% of the enzyme under these conditions compared with control levels. The inhibition of alkylsulfatase induction was highly specific for UTP. Some inhibition was observed with exogenous uracil, uridine, and pyrophosophate but only at concentrations greater than 1.0 mM. Exogenous UMP and UDP (2mM) had no effect.", "contents": "Effect of divalent cations on the inhibition of alkylsulfatase induction and the generation of ATP in Pseudomonas aeruginosa after exposure to exogenous uridine 5'-triphosphate. In the absence of added Mg2+, alkylsulfatase induction in resting cells of Pseudomonas aeruginosa was inhibited 17% by exogenous 0.05 mM UTP. Under these conditions, the cells converted UTP to ATP and rapid degradation of these nucleotides did not occur. In the presence of 0.73 mM Mg2+, 0.05 mM UTP repressed the synthesis of the enzyme by 71%. Under these conditions, the cells rapidly degraded both ATP derived from UTP as well as residual UTP. In the presence of Mg2+ and 0.1 mM UTP, full repression of alkylsulfatase formation occurred whereas Mg2+-depleted cell suspensions were still capable of synthesizing 47% of the enzyme under these conditions compared with control levels. The inhibition of alkylsulfatase induction was highly specific for UTP. Some inhibition was observed with exogenous uracil, uridine, and pyrophosophate but only at concentrations greater than 1.0 mM. Exogenous UMP and UDP (2mM) had no effect."}
{"id": "PMID:232004", "title": "Quantitative determination of cytomegalovirus IgG antibody by enzyme-linked immunosorbent assay (ELISA).", "content": "Quantitative determination of cytomegalovirus (CMV) human IgG antibody by ELISA performed in polystyrene trays was carried out and compared with results obtained by the routine complement fixation (CF) test. The antibody titres of all the sera determined by ELISA were higher than those detected by the CF test. Of the 27 sera negative (less than 1:8) by the CF test, 22 of them were also negative (less than 1:50) by ELISA. The other five CF negative sera were found to have low levels of antibody by ELISA. ELISA is a sensitive and specific assay for CMV antibody. The CMV antigen adsorbed readily to the microtitre plates and the test was simple to perform. The results of ELISA could be obtained in 5 to 6h. A description of the test procedure is given including the method of CMV antigen attachment to the plates. The possibility of using paired sera at a single dilution in the ELISA test to detect seroconversion is discussed.", "contents": "Quantitative determination of cytomegalovirus IgG antibody by enzyme-linked immunosorbent assay (ELISA). Quantitative determination of cytomegalovirus (CMV) human IgG antibody by ELISA performed in polystyrene trays was carried out and compared with results obtained by the routine complement fixation (CF) test. The antibody titres of all the sera determined by ELISA were higher than those detected by the CF test. Of the 27 sera negative (less than 1:8) by the CF test, 22 of them were also negative (less than 1:50) by ELISA. The other five CF negative sera were found to have low levels of antibody by ELISA. ELISA is a sensitive and specific assay for CMV antibody. The CMV antigen adsorbed readily to the microtitre plates and the test was simple to perform. The results of ELISA could be obtained in 5 to 6h. A description of the test procedure is given including the method of CMV antigen attachment to the plates. The possibility of using paired sera at a single dilution in the ELISA test to detect seroconversion is discussed."}
{"id": "PMID:232005", "title": "ICMSF methods studies. XII. Comparative study for the enumeration of Clostridium perfringens in feces.", "content": "As the second phase of an international comparative study for the enumeration of Clostridium perfringens, four methods were compared for \"total\" and spore counts of C. perfringens in fecal specimens: the SFP (Shahidi-Ferguson perfringens) agar (A), TSC (tryptose-sulfite-cycloserine) agar (B), SC (sulfite-cycloserine) agar (C), and neomycin blood agar (D) methods. In both the total and spore count procedures, the confirmed C. perfringens counts in method D were lower than in methods A, B, and C. Little differences among methods were found in the percentages of presumptive colonies confirmed as C. perfringens. The nonspecific counts in methods A and D were generally greater than in B and C, but nonspecific microorganisms did not interfere in the enumeration of C. perfringens spores by any of the four methods. In overall performance, methods B and C were superior to A and D. The mean C. perfringens spore count was only 0.17 log lower than the mean total count. Spore counts alone are, therefore, adequate in investigations of C. perfringens outbreaks.", "contents": "ICMSF methods studies. XII. Comparative study for the enumeration of Clostridium perfringens in feces. As the second phase of an international comparative study for the enumeration of Clostridium perfringens, four methods were compared for \"total\" and spore counts of C. perfringens in fecal specimens: the SFP (Shahidi-Ferguson perfringens) agar (A), TSC (tryptose-sulfite-cycloserine) agar (B), SC (sulfite-cycloserine) agar (C), and neomycin blood agar (D) methods. In both the total and spore count procedures, the confirmed C. perfringens counts in method D were lower than in methods A, B, and C. Little differences among methods were found in the percentages of presumptive colonies confirmed as C. perfringens. The nonspecific counts in methods A and D were generally greater than in B and C, but nonspecific microorganisms did not interfere in the enumeration of C. perfringens spores by any of the four methods. In overall performance, methods B and C were superior to A and D. The mean C. perfringens spore count was only 0.17 log lower than the mean total count. Spore counts alone are, therefore, adequate in investigations of C. perfringens outbreaks."}
{"id": "PMID:232006", "title": "Protective effect of polymyxin B sulfate in experimental enterobacterial infection in mice.", "content": "The mouse model of intraperitoneal enterobacterial sepsis was used to evaluate the anti-endotoxic effect of polymyxin B sulfate. Single or multiple therapeutic doses of polymyxin, administered either before or after lethal challenge with Serratia marcescens, produced statistically and clinically significant protective effects.", "contents": "Protective effect of polymyxin B sulfate in experimental enterobacterial infection in mice. The mouse model of intraperitoneal enterobacterial sepsis was used to evaluate the anti-endotoxic effect of polymyxin B sulfate. Single or multiple therapeutic doses of polymyxin, administered either before or after lethal challenge with Serratia marcescens, produced statistically and clinically significant protective effects."}
{"id": "PMID:232012", "title": "[A case of giant fibroadenoma of the breast in adolescence].", "content": "Starting from a personal observation of a giant fibroadenoma of the breast in a girl aged 13, the authors review the possible causes of massive swelling of the breast in adolescence. Next, they analyze the salient anatomoclinical aspects of giant fibroadenoma, benign phylloid cystosarcoma, and virginal mammary hypertrophy. The conclude that the surgeon should do everything possible to arrive at the histological diagnosis of fibroadenoma intraoperative--that is, extemporaneously--in order to avoid treating as a malignancy a possible benign phylloid cystosarcoma.", "contents": "[A case of giant fibroadenoma of the breast in adolescence]. Starting from a personal observation of a giant fibroadenoma of the breast in a girl aged 13, the authors review the possible causes of massive swelling of the breast in adolescence. Next, they analyze the salient anatomoclinical aspects of giant fibroadenoma, benign phylloid cystosarcoma, and virginal mammary hypertrophy. The conclude that the surgeon should do everything possible to arrive at the histological diagnosis of fibroadenoma intraoperative--that is, extemporaneously--in order to avoid treating as a malignancy a possible benign phylloid cystosarcoma."}
{"id": "PMID:232013", "title": "Morphometric method for evaluating the neurovirulence of live poliomyelitis vaccine.", "content": "A method for measuring morphological changes caused by residual neurovirulence in live poliomyelitis vaccine is described. The entire area of 16 standard parts of the central nervous system is measured directly under the microscope using a morphometric eyepiece grid. The method can be used to supplement the conventional system of scoring morphological lesions.", "contents": "Morphometric method for evaluating the neurovirulence of live poliomyelitis vaccine. A method for measuring morphological changes caused by residual neurovirulence in live poliomyelitis vaccine is described. The entire area of 16 standard parts of the central nervous system is measured directly under the microscope using a morphometric eyepiece grid. The method can be used to supplement the conventional system of scoring morphological lesions."}
{"id": "PMID:232014", "title": "[Bone maturity and physical performance].", "content": "We have examined the relation between physical performance (as measured with the CAHPER tests), bone age (Greulich and Pyl's wrist evaluation) and dental age (Garn's method). Our study included 164 boys and 149 girls aged from 7 to 11. In spite of interesting significant simple correlation between most of the CAHPER tests and bone age measurements for the pre-pubescent period, the latter remains of negligible value in predicting physical performance in the studied children when variables like chronological age, body height and body weight are already included in the prediction equation.", "contents": "[Bone maturity and physical performance]. We have examined the relation between physical performance (as measured with the CAHPER tests), bone age (Greulich and Pyl's wrist evaluation) and dental age (Garn's method). Our study included 164 boys and 149 girls aged from 7 to 11. In spite of interesting significant simple correlation between most of the CAHPER tests and bone age measurements for the pre-pubescent period, the latter remains of negligible value in predicting physical performance in the studied children when variables like chronological age, body height and body weight are already included in the prediction equation."}
{"id": "PMID:232016", "title": "Effect of age on angiotensin II receptors from rat brain.", "content": "1. Angiotensin II receptor binding was studied in specific regions of rat brain at different ages from birth to 14 weeks. 2. The number of specific angiotensin II receptors increased in all regions during the first 2 weeks of life and then decreased to adult levels. Peak numbers of receptors were up to 10 times the adult numbers. 3. The midbrain and thalamus-hypothalamus had maximum numbers of angiotensin II receptors at 2 weeks of age, whereas the rest of the brain regions had maximum number at 1 week. 4. Saralasin-infusion experiments suggested that circulating angiotensin-related peptides could reach brain angiotensin II receptors in 2 week old rats, but not in 6 week old rats. 5. It is postulated that the centrally mediated actions of circulating angiotensin II may be particularly important in the newborn.", "contents": "Effect of age on angiotensin II receptors from rat brain. 1. Angiotensin II receptor binding was studied in specific regions of rat brain at different ages from birth to 14 weeks. 2. The number of specific angiotensin II receptors increased in all regions during the first 2 weeks of life and then decreased to adult levels. Peak numbers of receptors were up to 10 times the adult numbers. 3. The midbrain and thalamus-hypothalamus had maximum numbers of angiotensin II receptors at 2 weeks of age, whereas the rest of the brain regions had maximum number at 1 week. 4. Saralasin-infusion experiments suggested that circulating angiotensin-related peptides could reach brain angiotensin II receptors in 2 week old rats, but not in 6 week old rats. 5. It is postulated that the centrally mediated actions of circulating angiotensin II may be particularly important in the newborn."}
{"id": "PMID:232017", "title": "Hormonal changes with long-term converting-enzyme inhibition by captopril in essential hypertension.", "content": "1. Captopril was shown to be as effective as hydrochlorothiazide in lowering the blood pressure in patients with moderately severe essential hypertension. 2. With the combination of captopril and hydrochlorothiazide satisfactory control of blood pressure was maintained over 8 months. 3. Inhibition of angiotensin converting enzyme by captopril in man was associated with falls in plasma angiotensin II and urinary aldosterone and rises in angiotensin I and plasma renin. 4. No change in venous concentrations of bradykinin could be demonstrated during therapy. 5. Captopril attenuated the hyperaldosteronism and hypokalaemia associated with diuretic therapy.", "contents": "Hormonal changes with long-term converting-enzyme inhibition by captopril in essential hypertension. 1. Captopril was shown to be as effective as hydrochlorothiazide in lowering the blood pressure in patients with moderately severe essential hypertension. 2. With the combination of captopril and hydrochlorothiazide satisfactory control of blood pressure was maintained over 8 months. 3. Inhibition of angiotensin converting enzyme by captopril in man was associated with falls in plasma angiotensin II and urinary aldosterone and rises in angiotensin I and plasma renin. 4. No change in venous concentrations of bradykinin could be demonstrated during therapy. 5. Captopril attenuated the hyperaldosteronism and hypokalaemia associated with diuretic therapy."}
{"id": "PMID:232019", "title": "Effects of an angiotensin converting enzyme inhibitor on psychosocial hypertension in mice.", "content": "1. Renin-associated, chronic psychosocial hypertension of 150-160 mmHg develops in groups of mice interacting socially in complex population cages. 2. The blood pressures of 16 males in a cage were measured and an intraperitoneal injection of the angiotensin coverting enzyme inhibitor captopril (SQ 14,225) was given. Three hours later blood pressures were measured again. 3. During the first 3 weeks of psychosocial hypertension SQ 14,225 was without effect. But at 1 month and subsequently up to 7 months, SQ 14,225 reduced blood pressure to the normal range of 120-130 mmHg. 4. Plasma renin activities were not related to the extent of blood pressure reduction by SQ 14,225. Hence other factors in addition to the renin-angiotensin mechanism play a part in maintaining chronic psychosocial hypertension.", "contents": "Effects of an angiotensin converting enzyme inhibitor on psychosocial hypertension in mice. 1. Renin-associated, chronic psychosocial hypertension of 150-160 mmHg develops in groups of mice interacting socially in complex population cages. 2. The blood pressures of 16 males in a cage were measured and an intraperitoneal injection of the angiotensin coverting enzyme inhibitor captopril (SQ 14,225) was given. Three hours later blood pressures were measured again. 3. During the first 3 weeks of psychosocial hypertension SQ 14,225 was without effect. But at 1 month and subsequently up to 7 months, SQ 14,225 reduced blood pressure to the normal range of 120-130 mmHg. 4. Plasma renin activities were not related to the extent of blood pressure reduction by SQ 14,225. Hence other factors in addition to the renin-angiotensin mechanism play a part in maintaining chronic psychosocial hypertension."}
{"id": "PMID:232020", "title": "A novel orally active converting-enzyme inhibitor YS 980: effects on blood pressure in spontaneously hypertensive rats.", "content": "1. The effects of long-term treatment with the angiotensin I converting-enzyme inhibitor YS 980 were examined in stroke-prone spontaneously hypertensive (sp-SH) rats. Development of hypertension was markedly blunted in the YS 980-treated animals. 2. Effective converting-enzyme inhibition was confirmed by significant increases in plasma angiotensin I (ANG I) and plasma renin concentration, inhibition of the pressor responses to intravenous ANG I and potentiation of the depressor responses to intravenous bradykinin. 3. Urinary free aldosterone excretion was decreased but no changes in urinary sodium and potassium excretion were observed. 4. The pressor responses to intravenous leucine-enkephalin were reduced. 5. The pressor responses to injection of ANG I and bradykinin into the lateral brain ventricle were unaltered. 6. We conclude that the antihypertensive action of YS 980 in sp-SH rats cannot be explained by the inhibition of the plasma renin-angiotensin system alone. Effects on other peptide systems must be considered.", "contents": "A novel orally active converting-enzyme inhibitor YS 980: effects on blood pressure in spontaneously hypertensive rats. 1. The effects of long-term treatment with the angiotensin I converting-enzyme inhibitor YS 980 were examined in stroke-prone spontaneously hypertensive (sp-SH) rats. Development of hypertension was markedly blunted in the YS 980-treated animals. 2. Effective converting-enzyme inhibition was confirmed by significant increases in plasma angiotensin I (ANG I) and plasma renin concentration, inhibition of the pressor responses to intravenous ANG I and potentiation of the depressor responses to intravenous bradykinin. 3. Urinary free aldosterone excretion was decreased but no changes in urinary sodium and potassium excretion were observed. 4. The pressor responses to intravenous leucine-enkephalin were reduced. 5. The pressor responses to injection of ANG I and bradykinin into the lateral brain ventricle were unaltered. 6. We conclude that the antihypertensive action of YS 980 in sp-SH rats cannot be explained by the inhibition of the plasma renin-angiotensin system alone. Effects on other peptide systems must be considered."}
{"id": "PMID:232021", "title": "Plasma noradrenaline correlates with alpha-adrenoreceptor-mediated vasoconstriction and blood pressure in patients with essential hypertension.", "content": "1. The relationships between plasma noradrenaline concentration at rest and blood pressure, as well as increase in forearm blood flow in response to a brachial artery infusion of the alpha-adrenoreceptor-blocking agent phentolamine, were investigated in hypertensive and normotensive subjects of similar age. 2. In 44 hypertensive patients plasma noradrenaline correlated with systolic, diastolic and mean blood pressures, but no difference in the mean plasma noradrenaline concentration was found. 3. In 11 patients and 14 normotensive subjects alpha-adrenoreceptor blockade resulted in a similar increase in forearm blood flow. Only in the patients, however, was this increase related to plasma noradrenaline and blood pressure. 4. In patients with established essential hypertension plasma noradrenaline can be considered to be a marker of alpha-adrenoreceptor-mediated vasoconstriction, which, in part, determines the height of the blood pressure.", "contents": "Plasma noradrenaline correlates with alpha-adrenoreceptor-mediated vasoconstriction and blood pressure in patients with essential hypertension. 1. The relationships between plasma noradrenaline concentration at rest and blood pressure, as well as increase in forearm blood flow in response to a brachial artery infusion of the alpha-adrenoreceptor-blocking agent phentolamine, were investigated in hypertensive and normotensive subjects of similar age. 2. In 44 hypertensive patients plasma noradrenaline correlated with systolic, diastolic and mean blood pressures, but no difference in the mean plasma noradrenaline concentration was found. 3. In 11 patients and 14 normotensive subjects alpha-adrenoreceptor blockade resulted in a similar increase in forearm blood flow. Only in the patients, however, was this increase related to plasma noradrenaline and blood pressure. 4. In patients with established essential hypertension plasma noradrenaline can be considered to be a marker of alpha-adrenoreceptor-mediated vasoconstriction, which, in part, determines the height of the blood pressure."}
{"id": "PMID:232022", "title": "Sympatho-adrenal and cardiovascular response to mental stress and orthostatic provocation in latent hypertension.", "content": "1. Seven latent hypertensive patients and seven matched controls were subjected to standardized mental stress and orthostatic provocation. 2. Mental stress increased blood pressure by approximately 25%, heart rate by 25 beats/min, plasma glycerol by 50% and plasma cyclic AMP by 25% in both groups. Plasma glucose and renin activity were unchanged. Plasma noradrenaline and adrenaline were essentially unchanged during stress. 3. There was an insignificant tendency towards higher noradrenaline levels in latent hypertensive subjects and two of these subjects displayed an exaggerated noradrenaline response to standing. 4. Our results indicate that the physiological responses to mental stress are caused by selective neuronal activation, rather than by generalized sympatho-adrenal activation. Latent hypertension does not seem to be associated with adrenergic hyperactivity or receptor supersensitivity, except possibly in individual cases.", "contents": "Sympatho-adrenal and cardiovascular response to mental stress and orthostatic provocation in latent hypertension. 1. Seven latent hypertensive patients and seven matched controls were subjected to standardized mental stress and orthostatic provocation. 2. Mental stress increased blood pressure by approximately 25%, heart rate by 25 beats/min, plasma glycerol by 50% and plasma cyclic AMP by 25% in both groups. Plasma glucose and renin activity were unchanged. Plasma noradrenaline and adrenaline were essentially unchanged during stress. 3. There was an insignificant tendency towards higher noradrenaline levels in latent hypertensive subjects and two of these subjects displayed an exaggerated noradrenaline response to standing. 4. Our results indicate that the physiological responses to mental stress are caused by selective neuronal activation, rather than by generalized sympatho-adrenal activation. Latent hypertension does not seem to be associated with adrenergic hyperactivity or receptor supersensitivity, except possibly in individual cases."}
{"id": "PMID:232023", "title": "Adrenocorticotropin inhibition of mineralocorticoid hormone production.", "content": "1. Adrenocorticotropin (ACTH)-induced steroidogenesis, obtained by continuous administration of ACTH for 3 days, produces in man (a) sustained elevations of plasma deoxycorticosterone and cortisol concentrations, (b) transient elevations of plasma aldosterone and 18-hydroxycorticosterone concentrations that return to near-control values, and (c) brisk initial increases in plasma 18-hydroxydeoxycorticosterone and corticosterone concentrations that fall to 20-68% of peak values 30 h thereafter. 2. Dexamethasone (8 mg/day, orally) treatment for 2 days in man permits a greater postural increase in plasma aldosterone and 18-hydroxycortisone concentrations. A dampening effect of ACTH is suggested. 3. An ACTH-initiated inhibition of 11 beta- and 18-hydroxylation is proposed to be operative in regulation of mineralocorticoid hormones.", "contents": "Adrenocorticotropin inhibition of mineralocorticoid hormone production. 1. Adrenocorticotropin (ACTH)-induced steroidogenesis, obtained by continuous administration of ACTH for 3 days, produces in man (a) sustained elevations of plasma deoxycorticosterone and cortisol concentrations, (b) transient elevations of plasma aldosterone and 18-hydroxycorticosterone concentrations that return to near-control values, and (c) brisk initial increases in plasma 18-hydroxydeoxycorticosterone and corticosterone concentrations that fall to 20-68% of peak values 30 h thereafter. 2. Dexamethasone (8 mg/day, orally) treatment for 2 days in man permits a greater postural increase in plasma aldosterone and 18-hydroxycortisone concentrations. A dampening effect of ACTH is suggested. 3. An ACTH-initiated inhibition of 11 beta- and 18-hydroxylation is proposed to be operative in regulation of mineralocorticoid hormones."}
{"id": "PMID:232024", "title": "Reactive hyper-reninaemia to angiotensin blockade identifies renovascular hypertension.", "content": "1. Saralasin and converting enzyme inhibitors SQ 20881 and captopril induced increases in plasma renin activity to greater than 14 ng h-1 ml-1 in 43 out of 44 patients with untreated renovascular hypertension when studied in the seated position and on normal sodium intake. This degree of response was absent in patients with normal-renin essential hypertension and present in only three out of 26 with high-renin essential hypertension. 2. Reductions of greater than approximately 9% in diastolic pressure in response to these three drugs occurred regularly in renovascular hypertension (95%) but also frequently in high-renin (65%) and normal-renin (26%) essential hypertension. 3. Prior sodium depletion abolished the specificity of the renin and depressor responses to angiotensin blockage for renovascular hypertension. 4. Some patients with bilateral renovascular and all with malignant hypertension also exhibited these responses to angiotensin blockade that are characteristic of unilateral renovascular hypertension.", "contents": "Reactive hyper-reninaemia to angiotensin blockade identifies renovascular hypertension. 1. Saralasin and converting enzyme inhibitors SQ 20881 and captopril induced increases in plasma renin activity to greater than 14 ng h-1 ml-1 in 43 out of 44 patients with untreated renovascular hypertension when studied in the seated position and on normal sodium intake. This degree of response was absent in patients with normal-renin essential hypertension and present in only three out of 26 with high-renin essential hypertension. 2. Reductions of greater than approximately 9% in diastolic pressure in response to these three drugs occurred regularly in renovascular hypertension (95%) but also frequently in high-renin (65%) and normal-renin (26%) essential hypertension. 3. Prior sodium depletion abolished the specificity of the renin and depressor responses to angiotensin blockage for renovascular hypertension. 4. Some patients with bilateral renovascular and all with malignant hypertension also exhibited these responses to angiotensin blockade that are characteristic of unilateral renovascular hypertension."}
{"id": "PMID:232025", "title": "Haemodynamics of ACTH-induced hypertension in sheep.", "content": "1. Administration of adrenocorticotropic hormone (ACTH) to sheep produced increases in mean arterial pressure within 24 h associated with an increase in cardiac output and cardiac rate. Both cardiac output and blood pressure remained elevated over the 5 days of ACTH treatment. 2. Administration of ACTH during beta-adrenoreceptor blockade resulted in an increase in blood pressure without changes in cardiac output at 24 h. 3. Administration of a combined steroid infusion over 5 days produced increases in cardiac output identical with the effects of ACTH but with a substantially smaller effect on blood pressure. 4. These data suggest that the observed changes in cardiac output produced by ACTH treatment may be associated with high blood concentrations of adrenocortical steroids rather than being necessary for the development of the hypertension.", "contents": "Haemodynamics of ACTH-induced hypertension in sheep. 1. Administration of adrenocorticotropic hormone (ACTH) to sheep produced increases in mean arterial pressure within 24 h associated with an increase in cardiac output and cardiac rate. Both cardiac output and blood pressure remained elevated over the 5 days of ACTH treatment. 2. Administration of ACTH during beta-adrenoreceptor blockade resulted in an increase in blood pressure without changes in cardiac output at 24 h. 3. Administration of a combined steroid infusion over 5 days produced increases in cardiac output identical with the effects of ACTH but with a substantially smaller effect on blood pressure. 4. These data suggest that the observed changes in cardiac output produced by ACTH treatment may be associated with high blood concentrations of adrenocortical steroids rather than being necessary for the development of the hypertension."}
{"id": "PMID:232026", "title": "Comparative beta-adrenoreceptor-blocking effects and pharmacokinetics or propranolol and pindolol in hypertensive Africans.", "content": "1. The beta-adrenoreceptor-blocking effects of pindolol were compared with those of propranolol and a placebo in a double-blind cross-over trial involving nine hypertensive African patients. 2. Heart rate, systolic blood pressure and diastolic blood pressure were measured at rest and immediately after exercise before and at intervals up to 6 h after oral administration of the drugs. In addition, plasma pindolol and propranolol concentrations were determined at the same intervals. 3. Pindolol diminished systolic blood pressure at rest and after exercise and antagonized exercise-induced tachycardia, but had no effect on resting heart rate. Propranolol diminished systolic blood pressure predominantly after exercise and reduced both resting and exercise heart rate. Both drugs had no effect on diastolic pressure. 4. The mean plasma concentration reached a peak at 2 h for each drug and this coincide with the interval at which maximal beta-adrenoreceptor-blocking effect was observed.", "contents": "Comparative beta-adrenoreceptor-blocking effects and pharmacokinetics or propranolol and pindolol in hypertensive Africans. 1. The beta-adrenoreceptor-blocking effects of pindolol were compared with those of propranolol and a placebo in a double-blind cross-over trial involving nine hypertensive African patients. 2. Heart rate, systolic blood pressure and diastolic blood pressure were measured at rest and immediately after exercise before and at intervals up to 6 h after oral administration of the drugs. In addition, plasma pindolol and propranolol concentrations were determined at the same intervals. 3. Pindolol diminished systolic blood pressure at rest and after exercise and antagonized exercise-induced tachycardia, but had no effect on resting heart rate. Propranolol diminished systolic blood pressure predominantly after exercise and reduced both resting and exercise heart rate. Both drugs had no effect on diastolic pressure. 4. The mean plasma concentration reached a peak at 2 h for each drug and this coincide with the interval at which maximal beta-adrenoreceptor-blocking effect was observed."}
{"id": "PMID:232027", "title": "Influence of selective and non-selective beta-adrenoreceptor blockade on the haemodynamic effect of adrenaline during combined antihypertensive drug therapy.", "content": "1. Haemodynamic effects of adrenaline were studied in 27 hypertensive patients, succesively during treatment with propranol and metoprolol. In 12 patients beta-adrenoreceptor blockade was combined with diuretics and in 15 patients the blockade was combined with vasodilators. 2. During propranolol adrenaline caused a marked pressor effect: there was a considerable rise in systolic as well as in diastolic blood pressure and a marked fall in heart rate. During metoprolol there was only a slight rise in blood pressure and an increase in heart rate. 3. Forearm blood flow was decreased by adrenaline during propranolol and was increased during metoprolol. Calculated vascular resistance showed opposite changes. 4. Results were essentially the same when beta-adrenoreceptor blockade was combined with diuretics or with vasodilators and did not differ from previous results obtained in patients treated by blockade alone. 5. If adrenaline infusion can be considered as a model for acute stress, our results seem to favour a selective beta 1-adrenoreceptor blocking agent over a non-selective one, even when the blocker is combined with a diuretic or a vasodilator.", "contents": "Influence of selective and non-selective beta-adrenoreceptor blockade on the haemodynamic effect of adrenaline during combined antihypertensive drug therapy. 1. Haemodynamic effects of adrenaline were studied in 27 hypertensive patients, succesively during treatment with propranol and metoprolol. In 12 patients beta-adrenoreceptor blockade was combined with diuretics and in 15 patients the blockade was combined with vasodilators. 2. During propranolol adrenaline caused a marked pressor effect: there was a considerable rise in systolic as well as in diastolic blood pressure and a marked fall in heart rate. During metoprolol there was only a slight rise in blood pressure and an increase in heart rate. 3. Forearm blood flow was decreased by adrenaline during propranolol and was increased during metoprolol. Calculated vascular resistance showed opposite changes. 4. Results were essentially the same when beta-adrenoreceptor blockade was combined with diuretics or with vasodilators and did not differ from previous results obtained in patients treated by blockade alone. 5. If adrenaline infusion can be considered as a model for acute stress, our results seem to favour a selective beta 1-adrenoreceptor blocking agent over a non-selective one, even when the blocker is combined with a diuretic or a vasodilator."}
{"id": "PMID:232028", "title": "Long-term effect of sotalol on plasma lipids.", "content": "1. We studied the effect on plasma lipids of sotalol given orally over a 12 month period to patients with essentially hypertension. 2. Plasma free fatty acid concentration was lower than initially at 1, 3, 6 and 12 months. The difference was significant (P less than 0.01) at 1 and 3 months. 3. Plasma cholesterol (VLDL + LDL-cholesterol) increased during treatment. Plasma total cholesterol increased from 5.49 +/- SD 0.94 mmol/l at the beginning to 6.37 +/- 1.10 mmol/l at 12 months (P less than 0.01). 4. HDL-cholesterol concentration and the ratio of HDL-cholesterol to total cholesterol decreased significantly. The ratios were 0.28 and 0.18 at the beginning and at 12 months respectively (P less than 0.001). 5. Plasma triglycerides increased simultaneously from 1.14 +/- 0.31 to 1.89 +/- 0.99 mmol/l (P less than 0.01).", "contents": "Long-term effect of sotalol on plasma lipids. 1. We studied the effect on plasma lipids of sotalol given orally over a 12 month period to patients with essentially hypertension. 2. Plasma free fatty acid concentration was lower than initially at 1, 3, 6 and 12 months. The difference was significant (P less than 0.01) at 1 and 3 months. 3. Plasma cholesterol (VLDL + LDL-cholesterol) increased during treatment. Plasma total cholesterol increased from 5.49 +/- SD 0.94 mmol/l at the beginning to 6.37 +/- 1.10 mmol/l at 12 months (P less than 0.01). 4. HDL-cholesterol concentration and the ratio of HDL-cholesterol to total cholesterol decreased significantly. The ratios were 0.28 and 0.18 at the beginning and at 12 months respectively (P less than 0.001). 5. Plasma triglycerides increased simultaneously from 1.14 +/- 0.31 to 1.89 +/- 0.99 mmol/l (P less than 0.01)."}
{"id": "PMID:232029", "title": "Effect of captopril on renal vascular tone in patients with essential hypertension.", "content": "1. The effect of acute inhibition of angiotensin-converting enzyme by captopril (50 mg) on renal haemodynamics and function was assessed in nine patients with essential hypertension on unrestricted sodium intake (n = 8) or low sodium diet (n = 1). 2. Captopril induced a rapid and significant decrease in arterial pressure, which was maximal within 60 min. 3. Effective renal plasma flow (ERPF) increased, glomerular filtration rate (GFR) did not change and filtration fraction (FF) decreased after captopril. No change in sodium excretion and a decrease in urinary potassium occurred. 4. In the patient on low sodium diet, captopril induced striking increases in GFR and ERPF (64 and 106% respectively). 5. The logarithm of baseline plasma renin activity was positvely correlated with the change in ERPF and negatively correlated with changes in FF and renal resistance. 6. The results indicate that in patients with essential hypertension angiotensin participates actively in the maintenance of renal vascular tone at the efferent arteriolar level. A possible influence of kinins remains to be defined.", "contents": "Effect of captopril on renal vascular tone in patients with essential hypertension. 1. The effect of acute inhibition of angiotensin-converting enzyme by captopril (50 mg) on renal haemodynamics and function was assessed in nine patients with essential hypertension on unrestricted sodium intake (n = 8) or low sodium diet (n = 1). 2. Captopril induced a rapid and significant decrease in arterial pressure, which was maximal within 60 min. 3. Effective renal plasma flow (ERPF) increased, glomerular filtration rate (GFR) did not change and filtration fraction (FF) decreased after captopril. No change in sodium excretion and a decrease in urinary potassium occurred. 4. In the patient on low sodium diet, captopril induced striking increases in GFR and ERPF (64 and 106% respectively). 5. The logarithm of baseline plasma renin activity was positvely correlated with the change in ERPF and negatively correlated with changes in FF and renal resistance. 6. The results indicate that in patients with essential hypertension angiotensin participates actively in the maintenance of renal vascular tone at the efferent arteriolar level. A possible influence of kinins remains to be defined."}
{"id": "PMID:232034", "title": "[Possible pathogenetic factors of gallstone formation in populations with a high standard of living (author's transl)].", "content": "The present work points out the variety of conditions favouring gallstone formation.--Recent research suggests that fibre-depleted, high-fat foods may lead to cholesterol gallstone formation in man. On the other side civilized diets contribute to the carcinogenesis of large bowel.--Experimental observations have indicated that hypovitaminosis C may favour pathogenesis of these diseases in a different way.", "contents": "[Possible pathogenetic factors of gallstone formation in populations with a high standard of living (author's transl)]. The present work points out the variety of conditions favouring gallstone formation.--Recent research suggests that fibre-depleted, high-fat foods may lead to cholesterol gallstone formation in man. On the other side civilized diets contribute to the carcinogenesis of large bowel.--Experimental observations have indicated that hypovitaminosis C may favour pathogenesis of these diseases in a different way."}
{"id": "PMID:232035", "title": "Insulin release and eflux of [32P]Phosphate from islets of rat Langerhans treated with iodoacetic acid and the anomers of D-glucose.", "content": "To clarify the insulin-releasing mechanism, we studied insulin release and the efflux of [32P]phosphate by glucose at 0.1 mM/min of gradient level or at 16.7 mM, and other metabolism in islets of rat Langerhans. When treated with 1 mM iodoacetic acid (IAA) plus the anomers of D-glucose at 2.8 mM for 6 min at 37 degrees C, islets elicited insulin at half the control rate under the step-wise stimulation by glucose and at the same rate as the control under the slow-rise stimulation by glucose. Using islets treated with IAA plus the alpha anomer at 16.7 mM, the step-wise stimulation secreted insulin at half a rate of the control and the slow-rise stimulation at the rate lower than the control, which was not significantly different from the control rate. Treatment with IAA plus the beta anomer at 16.7 mM inhibited insulin release under both types of stimulations by glucose. The step-wise stimulation caused the same rapid efflux of [32P]phosphate from IAA-treated islets  as from the control islets, except for islets treated with IAA plus the beta anomer at 16.7 mM. The rate of glucose utilization in islets was inhibited by all IAA-treatments to the same extent, being merely half the control rate. Treatments with IAA plus the anomers at 16.7 mM significantly reduced the formation of [3H]-cAMP and the activity of protein phosphokinase in islets, while in the presence of the anomers at 2.8 mM IAA produced no significant effect. Neither IAA-treatments altered the uptake of 45Ca and the ATP content in islets. The uptake of [14C]IAA was significantly enhanced by the presence of the beta anomer at 16.7 mM to two times the control level. On the basis of these results, we suggested that the B cell might contain both glucoreceptors and rate-sensors of glucose controlling insulin release and the former might be less sensitive to IAA as compared with the latter.", "contents": "Insulin release and eflux of [32P]Phosphate from islets of rat Langerhans treated with iodoacetic acid and the anomers of D-glucose. To clarify the insulin-releasing mechanism, we studied insulin release and the efflux of [32P]phosphate by glucose at 0.1 mM/min of gradient level or at 16.7 mM, and other metabolism in islets of rat Langerhans. When treated with 1 mM iodoacetic acid (IAA) plus the anomers of D-glucose at 2.8 mM for 6 min at 37 degrees C, islets elicited insulin at half the control rate under the step-wise stimulation by glucose and at the same rate as the control under the slow-rise stimulation by glucose. Using islets treated with IAA plus the alpha anomer at 16.7 mM, the step-wise stimulation secreted insulin at half a rate of the control and the slow-rise stimulation at the rate lower than the control, which was not significantly different from the control rate. Treatment with IAA plus the beta anomer at 16.7 mM inhibited insulin release under both types of stimulations by glucose. The step-wise stimulation caused the same rapid efflux of [32P]phosphate from IAA-treated islets  as from the control islets, except for islets treated with IAA plus the beta anomer at 16.7 mM. The rate of glucose utilization in islets was inhibited by all IAA-treatments to the same extent, being merely half the control rate. Treatments with IAA plus the anomers at 16.7 mM significantly reduced the formation of [3H]-cAMP and the activity of protein phosphokinase in islets, while in the presence of the anomers at 2.8 mM IAA produced no significant effect. Neither IAA-treatments altered the uptake of 45Ca and the ATP content in islets. The uptake of [14C]IAA was significantly enhanced by the presence of the beta anomer at 16.7 mM to two times the control level. On the basis of these results, we suggested that the B cell might contain both glucoreceptors and rate-sensors of glucose controlling insulin release and the former might be less sensitive to IAA as compared with the latter."}
{"id": "PMID:232036", "title": "The effects of dopamine on renal excretion of sodium, phosphate and cyclic AMP in thyroparathyroidectomized dogs.", "content": "With dopamine (0.5 microgram/kg/min) infusion into the renal artery of thyroparathyroidectomized dogs, urine output and inorganic phosphate excretion increased significantly (p less than 0.05), but the increase in sodium excretion was low and not statistically significant. However, natriuresis and phosphaturia due to the infusion of dopamine were accelerated more markedly by the pretreatment with phenoxybenzamine. Dopamine was infused into the renal artery indoses too small to affect renal hemodynamics (0.02-0.05 microgram/kg/min) after the treatment with phenoxybenzamine and alprenolol with the result that phosphate and sodium excretion increased significantly (p less than 0.05). The excretion rate of cAMP did not change. This suggests that the effect of dopamine on sodium and phosphate excretion is directly influenced by alpha adrenergic activity in the kidney. The mechanism of natriuresis and phosphaturia by dopamine is, however, independent of changes in parathyroid hormone and the adenyl cyclase-cAMP system.", "contents": "The effects of dopamine on renal excretion of sodium, phosphate and cyclic AMP in thyroparathyroidectomized dogs. With dopamine (0.5 microgram/kg/min) infusion into the renal artery of thyroparathyroidectomized dogs, urine output and inorganic phosphate excretion increased significantly (p less than 0.05), but the increase in sodium excretion was low and not statistically significant. However, natriuresis and phosphaturia due to the infusion of dopamine were accelerated more markedly by the pretreatment with phenoxybenzamine. Dopamine was infused into the renal artery indoses too small to affect renal hemodynamics (0.02-0.05 microgram/kg/min) after the treatment with phenoxybenzamine and alprenolol with the result that phosphate and sodium excretion increased significantly (p less than 0.05). The excretion rate of cAMP did not change. This suggests that the effect of dopamine on sodium and phosphate excretion is directly influenced by alpha adrenergic activity in the kidney. The mechanism of natriuresis and phosphaturia by dopamine is, however, independent of changes in parathyroid hormone and the adenyl cyclase-cAMP system."}
{"id": "PMID:232037", "title": "Glucagon secretion during the development of insulin-secreting tumors induced by streptozotocin and nicotinamide.", "content": "Serial oral glucose tolerance tests in rats treated with streptozotocin and nicotinamide showed that blood glucose levels after glucose loading were suppressed significantly 7 months after treatment as compared to those of earlier stages. Post-glucose plasma insulin levels were significantly elevated at the 9th to 12th month and concomitantly fasting plasma glucagon levels rose significantly. At that time pancreatic islet cell tumors were demonstrated in all of the rats in this experiment. Post-glucose plasma glucagon levels, however, did not show remarkable changes throughout the observation. In spite of hyperinsulinemia, post-glucose plasma glucagon levels of tumor-bearing rats were significantly lower than those of body weight adjusted controls. It is inferred from the study that secretory activity of pancreatic A-cells of tumor-bearing rats is restrained by excess insulin released from islet cell tumors.", "contents": "Glucagon secretion during the development of insulin-secreting tumors induced by streptozotocin and nicotinamide. Serial oral glucose tolerance tests in rats treated with streptozotocin and nicotinamide showed that blood glucose levels after glucose loading were suppressed significantly 7 months after treatment as compared to those of earlier stages. Post-glucose plasma insulin levels were significantly elevated at the 9th to 12th month and concomitantly fasting plasma glucagon levels rose significantly. At that time pancreatic islet cell tumors were demonstrated in all of the rats in this experiment. Post-glucose plasma glucagon levels, however, did not show remarkable changes throughout the observation. In spite of hyperinsulinemia, post-glucose plasma glucagon levels of tumor-bearing rats were significantly lower than those of body weight adjusted controls. It is inferred from the study that secretory activity of pancreatic A-cells of tumor-bearing rats is restrained by excess insulin released from islet cell tumors."}
{"id": "PMID:232038", "title": "Stimulation of pituitary-adrenocortical system by ginseng saponin.", "content": "Effects of preparations of saponin mixture and isolated ginsenosides, extracted from the root of Panax ginseng, on plasma corticotropin (ACTH) and corticosterone concentrations in rats were determined by the radioimmunoassay and competitive protein binding method. When ginseng saponin mixture was administered to rats intraperitoneally, plasma ACTH and corticosterone increased significantly 30, 60 and 90 min after the treatment. The kinetic pattern of the increase in plasma ACTH was almost parallel to that in plasma corticosterone. Isolated ginsenoside, protopanaxadiol or protopanaxatriol glycoside, also increased plasma corticosterone. The ginseng-induced increase in plasma corticosterone was suppressed by pretreatment with dexamethasone. Thus the ginseng saponin was found to act on the hypothalamus and/or hypophysis primarily, and stimulated ACTH secretion which resulted in increased synthesis of corticosterone in the adrenal cortex.", "contents": "Stimulation of pituitary-adrenocortical system by ginseng saponin. Effects of preparations of saponin mixture and isolated ginsenosides, extracted from the root of Panax ginseng, on plasma corticotropin (ACTH) and corticosterone concentrations in rats were determined by the radioimmunoassay and competitive protein binding method. When ginseng saponin mixture was administered to rats intraperitoneally, plasma ACTH and corticosterone increased significantly 30, 60 and 90 min after the treatment. The kinetic pattern of the increase in plasma ACTH was almost parallel to that in plasma corticosterone. Isolated ginsenoside, protopanaxadiol or protopanaxatriol glycoside, also increased plasma corticosterone. The ginseng-induced increase in plasma corticosterone was suppressed by pretreatment with dexamethasone. Thus the ginseng saponin was found to act on the hypothalamus and/or hypophysis primarily, and stimulated ACTH secretion which resulted in increased synthesis of corticosterone in the adrenal cortex."}
{"id": "PMID:232039", "title": "Some properties of hog thyroidal membrane-bound adenosine tri-phosphatase: proteolytic activation of Mg-dependent activity.", "content": "The ATPase preparations from the hog thyroid was preincubated with various amounts of trypsin. The activity of Mg-ATPase was consistently elevated. On the contrary, the Na, K-ATPase activity decreased with increasing amounts of trypsin. The effects were similar to those which were observed in the enzyme preparations treated with basis polyamino acids as previously reported. This phenomenon seemed to be specific in the preparations from the thyroid. The Mg-dependent activity was increased after pretreatment with trypsin or poly-L-lysine (PLL) when CTP, ITP and UTP were used as substrate. Thus the substrate specificity of Mg-ATPase was low. The enzyme-kinetics using ATP as substrate showed that the increase in activity was due to an increase in Vmax and not to a change in Km. The activity of Mg-ATPase was increased even after 30 min of preincubation with trypsin, while the Na, K-ATPase activity was almost diminished. These results suggest that the activity of Mg-ATPase in the preparation from the thyroid is specifically changed by the modification of the molecular environment of the enzyme with trypsin or basic polyamino acids.", "contents": "Some properties of hog thyroidal membrane-bound adenosine tri-phosphatase: proteolytic activation of Mg-dependent activity. The ATPase preparations from the hog thyroid was preincubated with various amounts of trypsin. The activity of Mg-ATPase was consistently elevated. On the contrary, the Na, K-ATPase activity decreased with increasing amounts of trypsin. The effects were similar to those which were observed in the enzyme preparations treated with basis polyamino acids as previously reported. This phenomenon seemed to be specific in the preparations from the thyroid. The Mg-dependent activity was increased after pretreatment with trypsin or poly-L-lysine (PLL) when CTP, ITP and UTP were used as substrate. Thus the substrate specificity of Mg-ATPase was low. The enzyme-kinetics using ATP as substrate showed that the increase in activity was due to an increase in Vmax and not to a change in Km. The activity of Mg-ATPase was increased even after 30 min of preincubation with trypsin, while the Na, K-ATPase activity was almost diminished. These results suggest that the activity of Mg-ATPase in the preparation from the thyroid is specifically changed by the modification of the molecular environment of the enzyme with trypsin or basic polyamino acids."}
{"id": "PMID:232040", "title": "Suppressive effect of pentagastrin on pituitary-adrenocortical secretion.", "content": "The effect of pentagastrin on the pituitary-adrenocortical secretion was examined in male rats. In the morning the intraperitoneal injection of this peptide produced a slight, but significant, decrease in the plasma corticosterone levels, but it had no effect on the evening rise due to circadian periodicity and the stress-induced elevation of the plasma corticosterone level. Following intracerebroventricular administration of pentagastrin, plasma corticosterone tended to decrease and in in vitro incubation of rat pituitary tissue the addition of pentagastrin elicited a suppressive effect on the ACTH release from the tissue into the medium. It was suggested that gastrin-like peptide might control the secretion of ACTH.", "contents": "Suppressive effect of pentagastrin on pituitary-adrenocortical secretion. The effect of pentagastrin on the pituitary-adrenocortical secretion was examined in male rats. In the morning the intraperitoneal injection of this peptide produced a slight, but significant, decrease in the plasma corticosterone levels, but it had no effect on the evening rise due to circadian periodicity and the stress-induced elevation of the plasma corticosterone level. Following intracerebroventricular administration of pentagastrin, plasma corticosterone tended to decrease and in in vitro incubation of rat pituitary tissue the addition of pentagastrin elicited a suppressive effect on the ACTH release from the tissue into the medium. It was suggested that gastrin-like peptide might control the secretion of ACTH."}
{"id": "PMID:232043", "title": "Clinical trials in cancer research.", "content": "This is a review paper which gives a discussion of various aspects of clinical trials in cancer research. Since the conduct of the first randomized controlled clinical trial in cancer patients in the mid-1950's, substantial progress has been made in the utilization of the clinical trial technique for the evaluation of therapeutic efficiacy. The important elements of a protocol are given with some discussion of items to be considered in designing a protocol. The types of clinical trial (phase I, II, III) are defined, and the place of each phase of study in the context of the search for new treatments is delineated. A comprehensive discussion is given of the elements in the comparative clinical trial (phase III), including objectives, consierations in planning (comparability of treatment groups stratification of patients, feasibility and size of study, and prospective versus retrospective studies). Brief descriptions are given of designs for comparative clinical trials and a trial in oat cell lung carcinoma is discussed in some detail. Finally, some comments and references are given concerning the analysis of clinical trials.", "contents": "Clinical trials in cancer research. This is a review paper which gives a discussion of various aspects of clinical trials in cancer research. Since the conduct of the first randomized controlled clinical trial in cancer patients in the mid-1950's, substantial progress has been made in the utilization of the clinical trial technique for the evaluation of therapeutic efficiacy. The important elements of a protocol are given with some discussion of items to be considered in designing a protocol. The types of clinical trial (phase I, II, III) are defined, and the place of each phase of study in the context of the search for new treatments is delineated. A comprehensive discussion is given of the elements in the comparative clinical trial (phase III), including objectives, consierations in planning (comparability of treatment groups stratification of patients, feasibility and size of study, and prospective versus retrospective studies). Brief descriptions are given of designs for comparative clinical trials and a trial in oat cell lung carcinoma is discussed in some detail. Finally, some comments and references are given concerning the analysis of clinical trials."}
{"id": "PMID:232044", "title": "An outbreak of foal perinatal mortality due to equid herpesvirus type 1: pathological observations.", "content": "Twenty-nine cases of EHV1 infection occurred on a property, mainly in full term foals. Some foals were stillborn, some were born alive but weak and soon died and others were healthy at birth, became ill and died within 3 days of birth. Apart from voluminous, oedematous and atelectic lungs there were no gross lesions. Microscopically the lungs showed oedema, pneumonitis and bronchiolitis with intranuclear inclusions and, in many of the foals that survived over 6 hours, there was also hyaline membrane formation. Microscopic lesions were also seen in the liver, adrenal, thymus and spleen of some of these foals.", "contents": "An outbreak of foal perinatal mortality due to equid herpesvirus type 1: pathological observations. Twenty-nine cases of EHV1 infection occurred on a property, mainly in full term foals. Some foals were stillborn, some were born alive but weak and soon died and others were healthy at birth, became ill and died within 3 days of birth. Apart from voluminous, oedematous and atelectic lungs there were no gross lesions. Microscopically the lungs showed oedema, pneumonitis and bronchiolitis with intranuclear inclusions and, in many of the foals that survived over 6 hours, there was also hyaline membrane formation. Microscopic lesions were also seen in the liver, adrenal, thymus and spleen of some of these foals."}
{"id": "PMID:232045", "title": "Involvement of glucocorticoids in the development of the secondary palate.", "content": "Genetic differences between various inbred strains of mice in the levels of glucocorticoid receptors embryonic in maxillary mesenchyme cells appear to be reflected in the magnitude of the responses to steroids in these cells. High levels of glucocorticoids cause significant growth inhibition in maxillary mesenchyme cells with subsequent alterations in the production of extracellular matrix components. The presence of higher levels of cytoplasmic glucocorticoid receptor proteins may be one factor which could predispose those strains such as A/J to a greater inhibition of craniofacial growth in vivo by glucocorticoids and therefore increase the frequency of cleft palate production. Furthermore, women with infertility treated with glucocorticoids to support pregnancy give birth to infants with a marked decrease in birth weight [98]. Pharmacologic doses of glucocorticoids can also cause a dramatic reduction in the growth of a number of fetal tissues in mice and humans. In fact, there is evidence that glucocorticoids may be a causative factor in the production of cleft palate in primates [52]. The nature of the molecular elements which determine the biochemical and physiologic responses to glucocorticoids in the palate still remains largely unknown. Although in the mouse there is some evidence to suggest that the major histocompatibility locus (H-2) might be involved, the level(s) at which this control is exerted is unknown. It is possible that this locus may regulate in some manner the level of glucocorticoid receptors and the response to glucocorticoids in the secondary palate. Moreover, there is evidence to suggest that other genes distinct from, but closely linked to the H-2 locus may be important in determining both the strain-dependent differences in susceptibility to glucocorticoid-induced cleft palate and the intracellular levels of cyclic AMP in the secondary palate. It is also apparent that glucocorticoids in conjunction with other hormones or growth factors such as epidermal growth factor and agents which regulate cyclic nucleotide metabolism are essential for the normal development of the secondary palate. Excesses or deficiencies in either the level of these growth regulators and/or in their receptors in specific fetal tissues at defined periods in development are likely to lead to certain fetal malformations. Definition and integration of the genetic, biochemical, and endocrine factors which are involved in the control of cellular growth as influenced by alterations in the composition of cell surface and extracellular matrix components should provide some insights into the events associated with normal palatogenesis.", "contents": "Involvement of glucocorticoids in the development of the secondary palate. Genetic differences between various inbred strains of mice in the levels of glucocorticoid receptors embryonic in maxillary mesenchyme cells appear to be reflected in the magnitude of the responses to steroids in these cells. High levels of glucocorticoids cause significant growth inhibition in maxillary mesenchyme cells with subsequent alterations in the production of extracellular matrix components. The presence of higher levels of cytoplasmic glucocorticoid receptor proteins may be one factor which could predispose those strains such as A/J to a greater inhibition of craniofacial growth in vivo by glucocorticoids and therefore increase the frequency of cleft palate production. Furthermore, women with infertility treated with glucocorticoids to support pregnancy give birth to infants with a marked decrease in birth weight [98]. Pharmacologic doses of glucocorticoids can also cause a dramatic reduction in the growth of a number of fetal tissues in mice and humans. In fact, there is evidence that glucocorticoids may be a causative factor in the production of cleft palate in primates [52]. The nature of the molecular elements which determine the biochemical and physiologic responses to glucocorticoids in the palate still remains largely unknown. Although in the mouse there is some evidence to suggest that the major histocompatibility locus (H-2) might be involved, the level(s) at which this control is exerted is unknown. It is possible that this locus may regulate in some manner the level of glucocorticoid receptors and the response to glucocorticoids in the secondary palate. Moreover, there is evidence to suggest that other genes distinct from, but closely linked to the H-2 locus may be important in determining both the strain-dependent differences in susceptibility to glucocorticoid-induced cleft palate and the intracellular levels of cyclic AMP in the secondary palate. It is also apparent that glucocorticoids in conjunction with other hormones or growth factors such as epidermal growth factor and agents which regulate cyclic nucleotide metabolism are essential for the normal development of the secondary palate. Excesses or deficiencies in either the level of these growth regulators and/or in their receptors in specific fetal tissues at defined periods in development are likely to lead to certain fetal malformations. Definition and integration of the genetic, biochemical, and endocrine factors which are involved in the control of cellular growth as influenced by alterations in the composition of cell surface and extracellular matrix components should provide some insights into the events associated with normal palatogenesis."}
{"id": "PMID:232048", "title": "The ultrastructure of renomedullary interstitial cells in short duration hypercalcemia induced by vitamin D3.", "content": "Under short duration hypercalcemia induced by pharmacological doses of vitamin D3 significant ultrastructural changes were observed in the renomedullary interstitial cells of rats. The most striking alteration was the degranulation of these cells accompanied with the increase in volume of the rough and smooth-surfaced endoplasmic reticulum, enlargement of the Golgi apparatus and occurence of osmiophilic inclusions probably of lipid nature in mitochondria. The ultrastructural changes can be regarded as an expression of the increase of a synthetic and secretory activity of the renomedullary interstitial cells and they may be associated with an enhanced production of prostaglandins or other lipid hormonal substances than prostaglandins under condition of hypercalcemia.", "contents": "The ultrastructure of renomedullary interstitial cells in short duration hypercalcemia induced by vitamin D3. Under short duration hypercalcemia induced by pharmacological doses of vitamin D3 significant ultrastructural changes were observed in the renomedullary interstitial cells of rats. The most striking alteration was the degranulation of these cells accompanied with the increase in volume of the rough and smooth-surfaced endoplasmic reticulum, enlargement of the Golgi apparatus and occurence of osmiophilic inclusions probably of lipid nature in mitochondria. The ultrastructural changes can be regarded as an expression of the increase of a synthetic and secretory activity of the renomedullary interstitial cells and they may be associated with an enhanced production of prostaglandins or other lipid hormonal substances than prostaglandins under condition of hypercalcemia."}
{"id": "PMID:232051", "title": "[Effects of diethyldithiocarbamate on ejaculatory inhibition and change in monoamine levels of accessory glands (author's transl)].", "content": "Effects of diethyldithiocarbamate(DDC) on erection and ejaculation were investigated and monoamine levels in central nervous system, gonad and accessory glands were determined in dogs. Intraperitoneal administration of 50, 75 and 100 mg/kg of DDC suppressed ejaculation 1 hour after administration, although penial erection did occur. This suppression of ejaculation was recovered to some extent 3 hours after DDC and completely recovered 24 hours after DDC. One hour after the administration of 100 mg/kg of DDC, noradrenaline (NA) level in the caudate and serotonin (5-HT) level in the posterior hypothalamus decreased significantly, as compared with the control. However, there were no significant changes in the regions of anterior hypothalamus and hippocampus which are known to play an important role in sexual behavior. In the epididymis, NA and adrenaline levels decreased significantly, though 5-HT levels increased, as compared with those of the control. In the prostate and posterior urethra, NA levels decreased significantly, as compared with the control. The seminal emission induced by hypogastric nerve stimulation induced a gradual rise in the posterior urethral pressure. When the pressure reached the maximum level, rhythmic alterations of the pressure considered to be a phenomenon associated with ejaculation occurred. DDC (100 mg/kg) abolished both seminal emission and rhythmic alterations of the posterior urethral pressure. These findings indicate that the sperm transport may be inhibited by decrease of NA level in accessory glands.", "contents": "[Effects of diethyldithiocarbamate on ejaculatory inhibition and change in monoamine levels of accessory glands (author's transl)]. Effects of diethyldithiocarbamate(DDC) on erection and ejaculation were investigated and monoamine levels in central nervous system, gonad and accessory glands were determined in dogs. Intraperitoneal administration of 50, 75 and 100 mg/kg of DDC suppressed ejaculation 1 hour after administration, although penial erection did occur. This suppression of ejaculation was recovered to some extent 3 hours after DDC and completely recovered 24 hours after DDC. One hour after the administration of 100 mg/kg of DDC, noradrenaline (NA) level in the caudate and serotonin (5-HT) level in the posterior hypothalamus decreased significantly, as compared with the control. However, there were no significant changes in the regions of anterior hypothalamus and hippocampus which are known to play an important role in sexual behavior. In the epididymis, NA and adrenaline levels decreased significantly, though 5-HT levels increased, as compared with those of the control. In the prostate and posterior urethra, NA levels decreased significantly, as compared with the control. The seminal emission induced by hypogastric nerve stimulation induced a gradual rise in the posterior urethral pressure. When the pressure reached the maximum level, rhythmic alterations of the pressure considered to be a phenomenon associated with ejaculation occurred. DDC (100 mg/kg) abolished both seminal emission and rhythmic alterations of the posterior urethral pressure. These findings indicate that the sperm transport may be inhibited by decrease of NA level in accessory glands."}
{"id": "PMID:232052", "title": "[Effect of thiol compounds on experimental liver damage (I). Preventive effect of tiopronin (2-mercaptopropionylglycine) on liver damage induced by carbon tetrachloride (author's transl)].", "content": "Effects of oral administration of tiopronin (2-mercaptopropionylglycine) on acute liver damage induced in rats by intraperitoneal administration of carbon tetrachloride (CCl4) were investigated. Tiopronin suppressed increase in serum transaminase activity, accumulation of liver triglyceride and decrease of liver glucose-6-phosphatase activity induced by CCl4. CCl4 induced a significant decrease of nonprotein thiol (NPSH) in the liver 24 hr after administration, but this decrease did not result in an increase of nonprotein disulfide in the liver. Tiopronin suppressed the decrease in NPSH induced by CCl4, but did not influence NPSH in normal rats 24 hr after administration. In addition to these biochemical findings, it was also noted that tiopronin prevented necrosis and decrease of glycogen in liver, as determined histologically. Other compounds such as cystamine, cysteine and glutathione proved to have a preventive effect on CCl4-induced liver damage as in the case of tiopronin. It was revealed that such preventive effect correlated to some extent with NPSH content in liver as well as serum transaminase activity and histological findings.", "contents": "[Effect of thiol compounds on experimental liver damage (I). Preventive effect of tiopronin (2-mercaptopropionylglycine) on liver damage induced by carbon tetrachloride (author's transl)]. Effects of oral administration of tiopronin (2-mercaptopropionylglycine) on acute liver damage induced in rats by intraperitoneal administration of carbon tetrachloride (CCl4) were investigated. Tiopronin suppressed increase in serum transaminase activity, accumulation of liver triglyceride and decrease of liver glucose-6-phosphatase activity induced by CCl4. CCl4 induced a significant decrease of nonprotein thiol (NPSH) in the liver 24 hr after administration, but this decrease did not result in an increase of nonprotein disulfide in the liver. Tiopronin suppressed the decrease in NPSH induced by CCl4, but did not influence NPSH in normal rats 24 hr after administration. In addition to these biochemical findings, it was also noted that tiopronin prevented necrosis and decrease of glycogen in liver, as determined histologically. Other compounds such as cystamine, cysteine and glutathione proved to have a preventive effect on CCl4-induced liver damage as in the case of tiopronin. It was revealed that such preventive effect correlated to some extent with NPSH content in liver as well as serum transaminase activity and histological findings."}
{"id": "PMID:232053", "title": "[Neuropharmacological studies on tolperisone hydrochloride (author's transl)].", "content": "Neuropharmacological properties of tolperisone hydrochloride (2,4'-dimethyl-3-piperidinopropiophenone hydrochloride) were investigated in mice, rats and cats. Tolperisone inhibited the spontaneous movement and methamphetamine-induced hyperactivity in mice and the ED50 was approx. 50 mg/kg, s.c. At this dose, tolperisone did not prolong the pentobarbital-induced sleeping time. Tolperisone inhibited convulsions induced by pentylenetetrazol, nicotine and maximum electric shock, but did not affect convulsions induced by strychnine and picrotoxin. Tolperisone induced muscle relaxation in mice and rats in several pharmacological tests, but did not affect neuro-muscular transmission. Tolperisone did not affect conditioned avoidance response in rats and methamphetamine-induced rotational behaviour in nigro-lesioned rats. Tolperisone reduced decerebrated rigidity in cats with i.v. administration of 5 approximately 10 mg/kg and intraduodenal administration of 50 approximately 100 mg/kg. Tolperisone elicited a slight drowsy pattern in the spontaneous EEG of cats at 5 approximately 10 mg/kg, i.v., and inhibited the EEG arousal response and pressor response to stimulation of mesencephalic reticular formation or posterior hypothalamic area. These results suggest that inhibition of the activity in the gamma pathway descending from the mesencephalic reticular formation may be involved in the mechanism of muscle relaxant action of tolperisone.", "contents": "[Neuropharmacological studies on tolperisone hydrochloride (author's transl)]. Neuropharmacological properties of tolperisone hydrochloride (2,4'-dimethyl-3-piperidinopropiophenone hydrochloride) were investigated in mice, rats and cats. Tolperisone inhibited the spontaneous movement and methamphetamine-induced hyperactivity in mice and the ED50 was approx. 50 mg/kg, s.c. At this dose, tolperisone did not prolong the pentobarbital-induced sleeping time. Tolperisone inhibited convulsions induced by pentylenetetrazol, nicotine and maximum electric shock, but did not affect convulsions induced by strychnine and picrotoxin. Tolperisone induced muscle relaxation in mice and rats in several pharmacological tests, but did not affect neuro-muscular transmission. Tolperisone did not affect conditioned avoidance response in rats and methamphetamine-induced rotational behaviour in nigro-lesioned rats. Tolperisone reduced decerebrated rigidity in cats with i.v. administration of 5 approximately 10 mg/kg and intraduodenal administration of 50 approximately 100 mg/kg. Tolperisone elicited a slight drowsy pattern in the spontaneous EEG of cats at 5 approximately 10 mg/kg, i.v., and inhibited the EEG arousal response and pressor response to stimulation of mesencephalic reticular formation or posterior hypothalamic area. These results suggest that inhibition of the activity in the gamma pathway descending from the mesencephalic reticular formation may be involved in the mechanism of muscle relaxant action of tolperisone."}
{"id": "PMID:232054", "title": "[Effectiveness of a new \"paramunity\" inducer (PIND-AVI) for human beings and animals].", "content": "Attenuated and by treatment with gamma rays inactivated avian Pox viruses (PIND-AVI) stimulate in man and animals selectively the T-lymphocytes. In this way PIND-AVI helps to repair a reduced reactivity of lymphocytes damaged by cytostatic chemotherapy: The lymphocyte stimulation by phytohemagglutinin could be normalized. In immunodeficient patients PIND-AVI showed very good effects in the treatment of herpes Virus infections.", "contents": "[Effectiveness of a new \"paramunity\" inducer (PIND-AVI) for human beings and animals]. Attenuated and by treatment with gamma rays inactivated avian Pox viruses (PIND-AVI) stimulate in man and animals selectively the T-lymphocytes. In this way PIND-AVI helps to repair a reduced reactivity of lymphocytes damaged by cytostatic chemotherapy: The lymphocyte stimulation by phytohemagglutinin could be normalized. In immunodeficient patients PIND-AVI showed very good effects in the treatment of herpes Virus infections."}
{"id": "PMID:232056", "title": "New cell line. Epithelial cell line and subline established from premalignant mouse mammary tissue.", "content": "A cell line and subline with epithelial characteristics were established from mouse mammary hyperplastic alveolar nodules (HAN). The cells do not grow in suspension cultures in vitro or form tumors in vivo. The cells do produce significant amounts of C-type and A-type virus and low amounts of plasminogen activator.", "contents": "New cell line. Epithelial cell line and subline established from premalignant mouse mammary tissue. A cell line and subline with epithelial characteristics were established from mouse mammary hyperplastic alveolar nodules (HAN). The cells do not grow in suspension cultures in vitro or form tumors in vivo. The cells do produce significant amounts of C-type and A-type virus and low amounts of plasminogen activator."}
{"id": "PMID:232057", "title": "Induction of alkaline phosphatase activity in HeLa cells by sodium butyrate.", "content": "The induction of HeLa cell alkaline phosphatase activity by sodium butyrate could be inhibited by the coadministration of caffeine or theophylline. The inhibitions were dose dependent, and at any given concentration the potency was theophylline greater than caffeine. Although the induction by sodium butyrate was more sensitive to the inhibition by the xanthines than was that produced by 5-iodo-2'-deoxyuridine, the magnitudes of the increases in cyclic AMP concentrations after treatment with the xanthines were similar in the inhibition of both types of induction. The induction of alkaline phosphatase activity by sodium butyrate also produced a shift in the thermostability pattern of the enzyme, with a proportionately greater increase in the heat-labile, rather than heat-stable, form of the activity.", "contents": "Induction of alkaline phosphatase activity in HeLa cells by sodium butyrate. The induction of HeLa cell alkaline phosphatase activity by sodium butyrate could be inhibited by the coadministration of caffeine or theophylline. The inhibitions were dose dependent, and at any given concentration the potency was theophylline greater than caffeine. Although the induction by sodium butyrate was more sensitive to the inhibition by the xanthines than was that produced by 5-iodo-2'-deoxyuridine, the magnitudes of the increases in cyclic AMP concentrations after treatment with the xanthines were similar in the inhibition of both types of induction. The induction of alkaline phosphatase activity by sodium butyrate also produced a shift in the thermostability pattern of the enzyme, with a proportionately greater increase in the heat-labile, rather than heat-stable, form of the activity."}
{"id": "PMID:232058", "title": "Ultrastructural and autoradiographic observations of hamster cheek pouch epithelium grown in vitro.", "content": "Epithelial outgrowths from hamster cheek pouch explants were cultured for varying periods of time up to 22 days. Growth of the epithelial sheets was monitored, employing colcemid for demonstrating mitotic activity and tritiated thymidine for DNA synthesis. Mitoses and thymidine uptake were observed among epithelial outgrowths at a considerable distance form the original explant. The epithelial nature of the growing cell sheets was confirmed, employing electron microscopic techniques. The cells exhibited the presence of tonofilaments, desmosomes, ribosomes, Golgi, mitochondria, and rough endoplasmic reticulum. The cultured explants were treated with cyclic nucleotides in order to investigate their modulatory effects on epithelial cell differentiation. Dibutyryl cAMP induced marked mitotic inhibition (46.3%) in our assay, which was increased to 57% with the addition of theophylline. Dibutyryl cGMP showed only a mild (5%) stimulatory effect on mitotic activity. Dibutyryl cAMP enhanced keratinization in the epithelial cell outgrowths with the biogenesis of keratohyalin granules, whereas dibutyryl cGMP did not produce any observable alterations.", "contents": "Ultrastructural and autoradiographic observations of hamster cheek pouch epithelium grown in vitro. Epithelial outgrowths from hamster cheek pouch explants were cultured for varying periods of time up to 22 days. Growth of the epithelial sheets was monitored, employing colcemid for demonstrating mitotic activity and tritiated thymidine for DNA synthesis. Mitoses and thymidine uptake were observed among epithelial outgrowths at a considerable distance form the original explant. The epithelial nature of the growing cell sheets was confirmed, employing electron microscopic techniques. The cells exhibited the presence of tonofilaments, desmosomes, ribosomes, Golgi, mitochondria, and rough endoplasmic reticulum. The cultured explants were treated with cyclic nucleotides in order to investigate their modulatory effects on epithelial cell differentiation. Dibutyryl cAMP induced marked mitotic inhibition (46.3%) in our assay, which was increased to 57% with the addition of theophylline. Dibutyryl cGMP showed only a mild (5%) stimulatory effect on mitotic activity. Dibutyryl cAMP enhanced keratinization in the epithelial cell outgrowths with the biogenesis of keratohyalin granules, whereas dibutyryl cGMP did not produce any observable alterations."}
{"id": "PMID:232059", "title": "Improved basal medium for Y-1 mouse adrenal cortex tumor cells in culture. I. Dependence of growth and steroid response on calcium ion concentration.", "content": "An improved basal medium is presented that required only minimal supplementation with dialyzed fetal bovine serum or bovine serum albumin and fetuin to be comparable to Ham's F-10, which requires 15% horse serum (HS) and 2.5% fetal bovine serum (FBS) for the growth and function of Y-1, mouse adrenal cortex tumor, cells. Cell monolayers maintained for up to 2 weeks without any protein supplementation have retained their steroid response to ACTH. The medium differs from Ham's F-10 in its buffer composition and higher calcium-ion concentration. This medium should be a useful adjunct to studies pertaining to steroid and lipid intermediary metabolism, the retention of a specialized physiological function in a chemically defined medium, and the mechanism of hormonal response.", "contents": "Improved basal medium for Y-1 mouse adrenal cortex tumor cells in culture. I. Dependence of growth and steroid response on calcium ion concentration. An improved basal medium is presented that required only minimal supplementation with dialyzed fetal bovine serum or bovine serum albumin and fetuin to be comparable to Ham's F-10, which requires 15% horse serum (HS) and 2.5% fetal bovine serum (FBS) for the growth and function of Y-1, mouse adrenal cortex tumor, cells. Cell monolayers maintained for up to 2 weeks without any protein supplementation have retained their steroid response to ACTH. The medium differs from Ham's F-10 in its buffer composition and higher calcium-ion concentration. This medium should be a useful adjunct to studies pertaining to steroid and lipid intermediary metabolism, the retention of a specialized physiological function in a chemically defined medium, and the mechanism of hormonal response."}
{"id": "PMID:232060", "title": "Concurrent replication of a papovavirus and a C-type virus in the CCL 33 porcine cell line.", "content": "A papovavirus, CCL 33 PV, isolated from a porcine cell line, CCL 33 (GT), was characterized. Based on a comparison of four isoenzyme systems, CCL 33 (GT) and CCL 33 (ATCC), obtained directly from the American Type Culture Collection, appeared to be the same. In addition to the previously characterized C-type virus of CCL 33 cultures, CCL 33 (GT) produced CCL 33 PV in high quantity, but CCL 33 (ATCC) produces a papovalike virus, presumably the same as CCL 33 PV, in barely detectable amounts. Serological results showed that CCL 33 PV is apparently identical to a papovavirus (SPV) isolated by Newman and Smith after inoculation of CCL 33 with concentrated porcine trypsin. These studies extend the characterization of this papovavirus, demonstrating that CCL 33 PV is weakly hemagglutinating after neuraminidase treatment, has a high affinity for a component of fetal bovine serum and is highly infectious in appropriate porcine cell systems rather than very defective as reported previously. Moreover, it was concluded from the data that CCL 33 PV is probably indigenous to the CCL 33 porcine cell line.", "contents": "Concurrent replication of a papovavirus and a C-type virus in the CCL 33 porcine cell line. A papovavirus, CCL 33 PV, isolated from a porcine cell line, CCL 33 (GT), was characterized. Based on a comparison of four isoenzyme systems, CCL 33 (GT) and CCL 33 (ATCC), obtained directly from the American Type Culture Collection, appeared to be the same. In addition to the previously characterized C-type virus of CCL 33 cultures, CCL 33 (GT) produced CCL 33 PV in high quantity, but CCL 33 (ATCC) produces a papovalike virus, presumably the same as CCL 33 PV, in barely detectable amounts. Serological results showed that CCL 33 PV is apparently identical to a papovavirus (SPV) isolated by Newman and Smith after inoculation of CCL 33 with concentrated porcine trypsin. These studies extend the characterization of this papovavirus, demonstrating that CCL 33 PV is weakly hemagglutinating after neuraminidase treatment, has a high affinity for a component of fetal bovine serum and is highly infectious in appropriate porcine cell systems rather than very defective as reported previously. Moreover, it was concluded from the data that CCL 33 PV is probably indigenous to the CCL 33 porcine cell line."}
{"id": "PMID:232073", "title": "Serological studies on the antigenic relationship between herpes simplex virus and varicella-zoster virus.", "content": "If crossreacting antibodies between varicella-zoster virus (VZV) and herpes simplex virus (HSV) exist, one would expect more positive reactions with VZV in a group of HSV positive patients than in a group of HSV negative patients. This statement can only apply to a group of individuals where positive and negative reactions with respect to HSV and VZV are evenly distributed. Such a distribution can only be found among children. Therefore, the relationship between HSV-1 and VZV was the only one which was considered in this investigation, since the incidence of HSV-2 antibodies in children is very rare. The sera from 197 children were examined using the neutralization test (NT), the complement fixation test (CFT) and the indirect immunofluorescent assay (IFT) and could be classified as either HSV positive (80) or HSV negative (117). The children's ages were similar in both groups. Approximately the same proportion of VZV positive sera was found in both groups when examined using IFT (53% in the HSV positive and 47% in the HSV negative group). However, when the CFT was applied the proportion of VZV positive sera in the two groups differed markedly (22% of the HSV positive sera and 38% of the HSV negative sera). These findings suggest that crossreactivity observed between HSV and VZV in acute HSV and VZV infections is evidently not dependent on crossreacting antibodies but is apparently confined to the cellular level of the immune response.", "contents": "Serological studies on the antigenic relationship between herpes simplex virus and varicella-zoster virus. If crossreacting antibodies between varicella-zoster virus (VZV) and herpes simplex virus (HSV) exist, one would expect more positive reactions with VZV in a group of HSV positive patients than in a group of HSV negative patients. This statement can only apply to a group of individuals where positive and negative reactions with respect to HSV and VZV are evenly distributed. Such a distribution can only be found among children. Therefore, the relationship between HSV-1 and VZV was the only one which was considered in this investigation, since the incidence of HSV-2 antibodies in children is very rare. The sera from 197 children were examined using the neutralization test (NT), the complement fixation test (CFT) and the indirect immunofluorescent assay (IFT) and could be classified as either HSV positive (80) or HSV negative (117). The children's ages were similar in both groups. Approximately the same proportion of VZV positive sera was found in both groups when examined using IFT (53% in the HSV positive and 47% in the HSV negative group). However, when the CFT was applied the proportion of VZV positive sera in the two groups differed markedly (22% of the HSV positive sera and 38% of the HSV negative sera). These findings suggest that crossreactivity observed between HSV and VZV in acute HSV and VZV infections is evidently not dependent on crossreacting antibodies but is apparently confined to the cellular level of the immune response."}
{"id": "PMID:232074", "title": "Generation of virus specific cytotoxic T cells in vitro. III. Spleen cells stimulated by viral antigens generate alloreactive cytotoxic T cells.", "content": "Cytotoxic T lymphocytes (CTL) from DBA/2 strain mice primed with Sendai virus (SV) in vivo were activated by secondary stimulation of spleen cells with viral antigens in vitro and analyzed for their target antigen specificity. These effector cells lysed syngeneic Sendai virus infected target cells, marginally a variety of non-infected targets and had a strong cytotoxic effect on H-2b targets. Studies on the antigenic requirements revealed that all SV preparations which generated specific CTL also induced the alloreactive populations. Similar results were found in the response to Newcastle disease virus (NDV) and some influenza A viruses; all these viruses were mitogenic for lymphocytes. Experiments on the cellular requirements indicated that virus specific and alloreactive cells can be separated by their requirements for help and for restimulation. By competition experiments both activities could be attributed to clearly separable T cell subpopulations. The induction mechanism of alloreactive T cells by viral antigens is discussed.", "contents": "Generation of virus specific cytotoxic T cells in vitro. III. Spleen cells stimulated by viral antigens generate alloreactive cytotoxic T cells. Cytotoxic T lymphocytes (CTL) from DBA/2 strain mice primed with Sendai virus (SV) in vivo were activated by secondary stimulation of spleen cells with viral antigens in vitro and analyzed for their target antigen specificity. These effector cells lysed syngeneic Sendai virus infected target cells, marginally a variety of non-infected targets and had a strong cytotoxic effect on H-2b targets. Studies on the antigenic requirements revealed that all SV preparations which generated specific CTL also induced the alloreactive populations. Similar results were found in the response to Newcastle disease virus (NDV) and some influenza A viruses; all these viruses were mitogenic for lymphocytes. Experiments on the cellular requirements indicated that virus specific and alloreactive cells can be separated by their requirements for help and for restimulation. By competition experiments both activities could be attributed to clearly separable T cell subpopulations. The induction mechanism of alloreactive T cells by viral antigens is discussed."}
{"id": "PMID:232075", "title": "Generation of effector cells from T cell subsets. I. Similar requirements for Lyt T cell subpopulations in the generation of alloreactive and H-2 restricted killer cells.", "content": "Lyt T cell subsets involved in the generation of H-2 restricted and alloreactive cytotoxic effector cells were analysed using anti Lyt antisera. Our data show that Lyt 1, 2, 3+ T cells are required for the induction of primary and secondary H-2 restricted and TNP-specific killer cells. In contrast, primary and secondary H-2 restricted and virus-specific T effector cells were obtained from selected Lyt 2, 3+ T cell populations and were not dependent on the presence of Lyt 1, 2, 3+ T cells. Allogeneic responses to selected K, I, or D region differences were obtained only in the presence of Lyt 1, 2, 3+ T cells; yet alloreactive killer cells were effectively generated from selected Lyt 2, 3+ T cell popluations deprived of Lyt 1, 2, 3+ T cells, when responder and stimulator cells differed at either K + D, K + I, I and D regionre is no qualitative difference between alloreactive and H-2 restricted cytotoxic responses in their requirements for particular Lyt T cell subsets. The findings indicate that the number of different antigenic determinants rather than their association with MHC self determinants is critical for the requirement of Lyt 1, 2, 3+ T cells during the sensitization phase.", "contents": "Generation of effector cells from T cell subsets. I. Similar requirements for Lyt T cell subpopulations in the generation of alloreactive and H-2 restricted killer cells. Lyt T cell subsets involved in the generation of H-2 restricted and alloreactive cytotoxic effector cells were analysed using anti Lyt antisera. Our data show that Lyt 1, 2, 3+ T cells are required for the induction of primary and secondary H-2 restricted and TNP-specific killer cells. In contrast, primary and secondary H-2 restricted and virus-specific T effector cells were obtained from selected Lyt 2, 3+ T cell populations and were not dependent on the presence of Lyt 1, 2, 3+ T cells. Allogeneic responses to selected K, I, or D region differences were obtained only in the presence of Lyt 1, 2, 3+ T cells; yet alloreactive killer cells were effectively generated from selected Lyt 2, 3+ T cell popluations deprived of Lyt 1, 2, 3+ T cells, when responder and stimulator cells differed at either K + D, K + I, I and D regionre is no qualitative difference between alloreactive and H-2 restricted cytotoxic responses in their requirements for particular Lyt T cell subsets. The findings indicate that the number of different antigenic determinants rather than their association with MHC self determinants is critical for the requirement of Lyt 1, 2, 3+ T cells during the sensitization phase."}
{"id": "PMID:232085", "title": "The role of angiotensin in the control of blood pressure during sodium depletion.", "content": "Sodium depletion was induced in dogs to raise plasma renin activity (PRA) from 1.11 to 26.48 ng/ml/hr. Little overall change in blood pressure (BP) occurred, but cardiac output (CO) and central venous pressure fell, while total peripheral resistance and heart rate (HR) increased. A nonapeptide converting enzyme inhibitor (CEI) produced a fall in BP which was linearly related to log. PRA; the intercept with PRA was at 1.05 ng/ml/hr, close to the average value for dogs on a normal diet. The fall in BP with this agent was not accompanied by an increase in HR or CO. When Sar1-Ala8 angiotensin II was used to antagonize the action of angiotensin, the fall in BP was also linearly related to log. PRA. However, for a given level of PRA this fall in BP was less than that achieved with CEI and the intercept of BP fall with PRA was 2.6 ng/ml/hr. Again with this agent there was little change in HR or CO as BP was reduced. Thus, both antagonists lowered peripheral resistance without exciting the homeostatic reflexes indicating that, as PRA rose above the normal resting level, the angiotensin generated had both a direct and indirect effect in maintaining BP.", "contents": "The role of angiotensin in the control of blood pressure during sodium depletion. Sodium depletion was induced in dogs to raise plasma renin activity (PRA) from 1.11 to 26.48 ng/ml/hr. Little overall change in blood pressure (BP) occurred, but cardiac output (CO) and central venous pressure fell, while total peripheral resistance and heart rate (HR) increased. A nonapeptide converting enzyme inhibitor (CEI) produced a fall in BP which was linearly related to log. PRA; the intercept with PRA was at 1.05 ng/ml/hr, close to the average value for dogs on a normal diet. The fall in BP with this agent was not accompanied by an increase in HR or CO. When Sar1-Ala8 angiotensin II was used to antagonize the action of angiotensin, the fall in BP was also linearly related to log. PRA. However, for a given level of PRA this fall in BP was less than that achieved with CEI and the intercept of BP fall with PRA was 2.6 ng/ml/hr. Again with this agent there was little change in HR or CO as BP was reduced. Thus, both antagonists lowered peripheral resistance without exciting the homeostatic reflexes indicating that, as PRA rose above the normal resting level, the angiotensin generated had both a direct and indirect effect in maintaining BP."}
{"id": "PMID:232090", "title": "A serological survey of St Lucia.", "content": "A serological survey of a random sample of 541 of the population of St Lucia was undertaken. The prevalence of antibodies to dengue, herpes virus, VZ, rotavirus, rubella and syphilis is described and compared with other communities.", "contents": "A serological survey of St Lucia. A serological survey of a random sample of 541 of the population of St Lucia was undertaken. The prevalence of antibodies to dengue, herpes virus, VZ, rotavirus, rubella and syphilis is described and compared with other communities."}
{"id": "PMID:232083", "title": "Angiotensin and sodium balance: their role in chronic two-kidney Goldblatt hypertension.", "content": "The purpose of this study was twofold: 1) to determine whether the failure of rats with chronic renovascular hypertension to respond to the angiotensin II antagonist (AIIA) with a decrease in mean blood pressure (BP) was dur to the agonistic effect of the antagonist; and, 2) if this was not the case, to examine whether a positive sodium balance impaired the reversal of the hypertension, after unclamping, in the rats that did not respond to angiotensin inhibitors. For this purpose, rats with chronic, two-kidney Goldblatt hypertension (one renal artery clamped and contralateral untouched) were tested for their BP response to the AIIA (1-Sar-8-Ala-angiotensin II) and to the converting enzyme inhibitor (CEI) SQ20,881, which is devoid of agonistic effect. Approximately 50% of the rats responded to both inhibitors either with no change or with a decrease in BP of less than 20 mm Hg (nonresponders). The other 50% had a decrease in BP of 20 mm Hg or greater (responders). The decrease in BP produced by the AIIA and the CEI correlated significantly (r = 0.76). Nonresponders to both inhibitors were unclamped or sham unclamped. A positive sodium balance was produced before surgery by injecting either 400 or 1000 microEq of sodium and was maintained for 12 hours. Direct BP significantly decreased 12 hours after surgery in the unclamped rats despite a continuous positive sodium balance. In the sham unclamped rats, BP did not change. These data indicate that the failure to respond to the AIIA is not due to the agonistic effect of this peptide. Furthermore, these data suggest that a positive sodium balance is not a major pathogenetic factor in maintaining the high BP in the nonresponder rats, since a positive sodium balance failed to maintain the hypertension after unclamping.", "contents": "Angiotensin and sodium balance: their role in chronic two-kidney Goldblatt hypertension. The purpose of this study was twofold: 1) to determine whether the failure of rats with chronic renovascular hypertension to respond to the angiotensin II antagonist (AIIA) with a decrease in mean blood pressure (BP) was dur to the agonistic effect of the antagonist; and, 2) if this was not the case, to examine whether a positive sodium balance impaired the reversal of the hypertension, after unclamping, in the rats that did not respond to angiotensin inhibitors. For this purpose, rats with chronic, two-kidney Goldblatt hypertension (one renal artery clamped and contralateral untouched) were tested for their BP response to the AIIA (1-Sar-8-Ala-angiotensin II) and to the converting enzyme inhibitor (CEI) SQ20,881, which is devoid of agonistic effect. Approximately 50% of the rats responded to both inhibitors either with no change or with a decrease in BP of less than 20 mm Hg (nonresponders). The other 50% had a decrease in BP of 20 mm Hg or greater (responders). The decrease in BP produced by the AIIA and the CEI correlated significantly (r = 0.76). Nonresponders to both inhibitors were unclamped or sham unclamped. A positive sodium balance was produced before surgery by injecting either 400 or 1000 microEq of sodium and was maintained for 12 hours. Direct BP significantly decreased 12 hours after surgery in the unclamped rats despite a continuous positive sodium balance. In the sham unclamped rats, BP did not change. These data indicate that the failure to respond to the AIIA is not due to the agonistic effect of this peptide. Furthermore, these data suggest that a positive sodium balance is not a major pathogenetic factor in maintaining the high BP in the nonresponder rats, since a positive sodium balance failed to maintain the hypertension after unclamping."}
{"id": "PMID:232087", "title": "Role of renin-angiotensin system in chronic renal hypertensive rats.", "content": "The role of renin-angiotensin system has been examined in the maintenance of hypertension in acute and chronic two-kidney (36 weeks) and chronic one-kidney (12 weeks) Goldblatt hypertensive rats using three inhibitors of this system. The inhibitors used were URI-73A, a synthetic analog of lysophosphatidylethanolamine, which inhibits renin both in vivo and in vitro, SQ14,225, a potent converting enzyme inhibitor, and [Sar1, Thr8] angiotensin II, an angiotensin II antagonist. When the inhibitors were administered in acute (high renin) hypertensive rats, they all lowered blood pressure significantly. However, in the chronic (low renin) hypertensive phase, both renin and converting enzyme inhibitors lowered blood pressure, whereas, Sar1, Thr8 failed to lower blood pressure. The renin inhibitor lowered plasma renin activity (PRA), and SQ14,225 and [Sar1, Thr8] Ang II increased PRA. Further studies on water and electrolyte balance with one-kidney model hypertensive and uninephrectomized control rats showed no change in plasma volume. However, there was increased 24-hour urinary output and increased sodium excretion. This study indicates that in chronic renal hypertensive rats, blood pressure reduction is possible by either renin on converting enzyme inhibitor, but not by angiotensin antagonists. Since volume did not change either during the development or reversal of hypertension, volume did not appear to play a major role in the maintenance of hypertension.", "contents": "Role of renin-angiotensin system in chronic renal hypertensive rats. The role of renin-angiotensin system has been examined in the maintenance of hypertension in acute and chronic two-kidney (36 weeks) and chronic one-kidney (12 weeks) Goldblatt hypertensive rats using three inhibitors of this system. The inhibitors used were URI-73A, a synthetic analog of lysophosphatidylethanolamine, which inhibits renin both in vivo and in vitro, SQ14,225, a potent converting enzyme inhibitor, and [Sar1, Thr8] angiotensin II, an angiotensin II antagonist. When the inhibitors were administered in acute (high renin) hypertensive rats, they all lowered blood pressure significantly. However, in the chronic (low renin) hypertensive phase, both renin and converting enzyme inhibitors lowered blood pressure, whereas, Sar1, Thr8 failed to lower blood pressure. The renin inhibitor lowered plasma renin activity (PRA), and SQ14,225 and [Sar1, Thr8] Ang II increased PRA. Further studies on water and electrolyte balance with one-kidney model hypertensive and uninephrectomized control rats showed no change in plasma volume. However, there was increased 24-hour urinary output and increased sodium excretion. This study indicates that in chronic renal hypertensive rats, blood pressure reduction is possible by either renin on converting enzyme inhibitor, but not by angiotensin antagonists. Since volume did not change either during the development or reversal of hypertension, volume did not appear to play a major role in the maintenance of hypertension."}
{"id": "PMID:232091", "title": "Melanotic neuroectodermal tumor of infancy (pigmented melanoameloblastoma).", "content": "The paper describes a large pigmented maxillary tumor in a 46-day-old infant. The histological examination showed the tumor to be a melanotic neuroectodermal tumor of infancy (MNTI). No raised urinary levels of vanilmandelic acid could be shown. The tumor was surgically removed and during a 5 1/2-year follow-up period there was no clinical evidence of recurrence. The origin, behavior and treatment of these rare tumors are discussed.", "contents": "Melanotic neuroectodermal tumor of infancy (pigmented melanoameloblastoma). The paper describes a large pigmented maxillary tumor in a 46-day-old infant. The histological examination showed the tumor to be a melanotic neuroectodermal tumor of infancy (MNTI). No raised urinary levels of vanilmandelic acid could be shown. The tumor was surgically removed and during a 5 1/2-year follow-up period there was no clinical evidence of recurrence. The origin, behavior and treatment of these rare tumors are discussed."}
{"id": "PMID:232088", "title": "Exchangeable sodium in angiotensinogenic and nonangiotensinogenic renovascular hypertension.", "content": "Previous studies have suggested that angiotensin II and sodium can act as alternative mechanisms in maintaining high blood pressure in chronic renovascular hypertension, In the present study, exchangeable sodium was measured in rats in which angiotensin II has been confirmed or excluded as the main cause of the hypertension. To determine the degree of participation of angiotensin II in the maintenance of the high blood pressure, we studied the mean blood pressure response to an angiotensin antagonist (1-Sar-8-Ala-angiotensin II) and to a converting enzyme inhibitor (SQ20,881). Rats with a decrease in blood pressure of less than 20 mm Hg, in response to both inhibitors, were classified as nonresponders; those with a decrease of 20 mm Hg or more, as responders. Fifty percent of the rats with two-kidney hypertension were nonresponders, and they had lower blood pressure and plasma renin activity than the responders. Further, these two-kidney, hypertensive, nonresponder rats had normal exchangeable sodium. The two-kidney hypertensive responders, on the other hand, had significantly higher exchangeable sodium than both the two-kidney, hypertensive nonresponders and the two-kidney control rats. These results suggest that angiotensin II and exchangeable sodium do not play a major role in the maintenance of the high blood pressure in the two-kidney hypertensive nonresponders. However, there appears to be an abnormal relationship between renin and exchangeable sodium in the two-kidney hypertensive responders that could contribute to the maintenance of the hypertension.", "contents": "Exchangeable sodium in angiotensinogenic and nonangiotensinogenic renovascular hypertension. Previous studies have suggested that angiotensin II and sodium can act as alternative mechanisms in maintaining high blood pressure in chronic renovascular hypertension, In the present study, exchangeable sodium was measured in rats in which angiotensin II has been confirmed or excluded as the main cause of the hypertension. To determine the degree of participation of angiotensin II in the maintenance of the high blood pressure, we studied the mean blood pressure response to an angiotensin antagonist (1-Sar-8-Ala-angiotensin II) and to a converting enzyme inhibitor (SQ20,881). Rats with a decrease in blood pressure of less than 20 mm Hg, in response to both inhibitors, were classified as nonresponders; those with a decrease of 20 mm Hg or more, as responders. Fifty percent of the rats with two-kidney hypertension were nonresponders, and they had lower blood pressure and plasma renin activity than the responders. Further, these two-kidney, hypertensive, nonresponder rats had normal exchangeable sodium. The two-kidney hypertensive responders, on the other hand, had significantly higher exchangeable sodium than both the two-kidney, hypertensive nonresponders and the two-kidney control rats. These results suggest that angiotensin II and exchangeable sodium do not play a major role in the maintenance of the high blood pressure in the two-kidney hypertensive nonresponders. However, there appears to be an abnormal relationship between renin and exchangeable sodium in the two-kidney hypertensive responders that could contribute to the maintenance of the hypertension."}
{"id": "PMID:232084", "title": "Hemodynamic and antihypertensive effects of captopril, an orally active angiotensin converting enzyme inhibitor.", "content": "Captopril inhibits angiotensin II formation and bradykinin degradation in vivo. Eleven patients with essential hypertension (EH) and four patients with renovascular hypertension (RVH) were treated with captopril for periods ranging from 3 days to 12 months. All patients had a diastolic blood pressure (DBP) over 95 mm Hg after receiving a placebo for 3 days. Captopril given in ascending doses (10-1000 mg/day) caused normalization of blood pressure in all but three patients, one with severe RVH whose pressure fell 11%, one patient with severe EH, whose pressure fell 27%, and one with EH whose blood pressure fell 8.5%. The average control DBP in patients with EH was 113.7 +/- 5.5 (SE) mm Hg and fell to 89.9 +/- 3.6 mm Hg (p less than 0.001), while DBP in patients with RVH fell from 110.7 +/- 7.6 mm Hg to 94.5 +/- 8.2 (p less than 0.005). All patients were studied in balance on a 100 mEq sodium (Na) diet. Plasma renin activity (PRA) versus 24-hour urinary Na excretion increased sevenfold during therapy while converting enzyme activity fell by about one half. The magnitude of the blood pressure response was not related to control PRA. Cardiac output was estimated by echocardiography during placebo administration and during maintenance therapy with captopril. A significant change was not observed. Total peripheral resistance fell an average of 18.9% (p less than 0.05) in 11 of the 13 patients in whom the measurement could be made. It is concluded that captopril effectively lowers blood pressure in patients with EH or RHV by reducing total peripheral resistance.", "contents": "Hemodynamic and antihypertensive effects of captopril, an orally active angiotensin converting enzyme inhibitor. Captopril inhibits angiotensin II formation and bradykinin degradation in vivo. Eleven patients with essential hypertension (EH) and four patients with renovascular hypertension (RVH) were treated with captopril for periods ranging from 3 days to 12 months. All patients had a diastolic blood pressure (DBP) over 95 mm Hg after receiving a placebo for 3 days. Captopril given in ascending doses (10-1000 mg/day) caused normalization of blood pressure in all but three patients, one with severe RVH whose pressure fell 11%, one patient with severe EH, whose pressure fell 27%, and one with EH whose blood pressure fell 8.5%. The average control DBP in patients with EH was 113.7 +/- 5.5 (SE) mm Hg and fell to 89.9 +/- 3.6 mm Hg (p less than 0.001), while DBP in patients with RVH fell from 110.7 +/- 7.6 mm Hg to 94.5 +/- 8.2 (p less than 0.005). All patients were studied in balance on a 100 mEq sodium (Na) diet. Plasma renin activity (PRA) versus 24-hour urinary Na excretion increased sevenfold during therapy while converting enzyme activity fell by about one half. The magnitude of the blood pressure response was not related to control PRA. Cardiac output was estimated by echocardiography during placebo administration and during maintenance therapy with captopril. A significant change was not observed. Total peripheral resistance fell an average of 18.9% (p less than 0.05) in 11 of the 13 patients in whom the measurement could be made. It is concluded that captopril effectively lowers blood pressure in patients with EH or RHV by reducing total peripheral resistance."}
{"id": "PMID:232092", "title": "Regional odontodysplasia.", "content": "Regional odontodysplasia was diagnosed in a girl aged 6 with lesions of a number of deciduous and permanent teeth in the right lower and upper quadrants. The literature comprises reports on some 50 cases of regional odontodysplasia, including only one patient who also showed involvement of both the maxilla and the mandible.", "contents": "Regional odontodysplasia. Regional odontodysplasia was diagnosed in a girl aged 6 with lesions of a number of deciduous and permanent teeth in the right lower and upper quadrants. The literature comprises reports on some 50 cases of regional odontodysplasia, including only one patient who also showed involvement of both the maxilla and the mandible."}
{"id": "PMID:232095", "title": "Type 1 diabetes and Coxsackie virus infection.", "content": "The role played by viruses in the aetiopathogenesis of type 1 diabetes mellitus has been studied by several authors; in particular the importance of Coxsackie virus B4 infection has been stated by some authors and not confirmed by others. 43 diabetic children were studied at the time of the diagnosis of the disease. No viruses could be isolated from stools; the titres of anti-Coxsackie viruses B1 to 6 complement fixing antibodies and anti-Coxsackie virus B4 neutralizing antibodies, compared to controls, indicated that Coxsackie virus infection was not associated with the onset of diabetes in these children. A cross-reaction with anti-Coxsackie viruses sera and a human pancreas demonstrated that there are not antigens in common between these viruses and the human pancreas.", "contents": "Type 1 diabetes and Coxsackie virus infection. The role played by viruses in the aetiopathogenesis of type 1 diabetes mellitus has been studied by several authors; in particular the importance of Coxsackie virus B4 infection has been stated by some authors and not confirmed by others. 43 diabetic children were studied at the time of the diagnosis of the disease. No viruses could be isolated from stools; the titres of anti-Coxsackie viruses B1 to 6 complement fixing antibodies and anti-Coxsackie virus B4 neutralizing antibodies, compared to controls, indicated that Coxsackie virus infection was not associated with the onset of diabetes in these children. A cross-reaction with anti-Coxsackie viruses sera and a human pancreas demonstrated that there are not antigens in common between these viruses and the human pancreas."}
{"id": "PMID:232097", "title": "Extrarenal Wilms' tumour: a review and case report.", "content": "A case of extrarenal nephroblastoma in a girl aged 5 1/2 years is reported. From a review of the few other published instances, it is apparent that extrarenal Wilms' tumours are rare occurrences which present a number of unanswered questions of great theoretical interest, particularly as far as their relation to teratomas is concerned.", "contents": "Extrarenal Wilms' tumour: a review and case report. A case of extrarenal nephroblastoma in a girl aged 5 1/2 years is reported. From a review of the few other published instances, it is apparent that extrarenal Wilms' tumours are rare occurrences which present a number of unanswered questions of great theoretical interest, particularly as far as their relation to teratomas is concerned."}
{"id": "PMID:232102", "title": "Potassium fluxes and ouabain binding in growing, density-inhibited and Rous sarcoma virus-transformed chicken embryo cells.", "content": "Potassium fluxes, ouabain binding, and Na+ and K+ intracellular concentrations were determined for cultures of growing normal, density-inhibited and Rous sarcoma virus-transformed chicken embryo fibroblasts. No significant differences in K+ influx or ouabain binding were detected between growing normal cells and Rous sarcoma virus-transformed cells; however, ouabain binding and ouabain-sensitive K+ influx were 1.5- to 1.8-fold lower in density-inhibited cells. Thus, potassium influx in this system can be classified as a growth-related, but not transformation-specific change. As determined by both flame photometry and radioisotopic (42K) equilibration, growing normal and density-inhibited cells had similar potassium contents, whereas transformed cells exhibited 1.4-fold higher potassium levels. Sodium ion levels, as measured by flame photometry, were also 2- to 4.5-fold higher in transformed than normal or density-inhibited cells. Complementary studies of potassium efflux showed a 1.3- to 1.5-fold higher rate (based on the percentage of pool exiting the cell) in growing normal versus density-inhibited or transformed fibroblasts. Because of the larger potassium pool in transformed cells, efflux based on absolute number of potassium ions is similar in normal and transformed chicken embryo fibroblasts.", "contents": "Potassium fluxes and ouabain binding in growing, density-inhibited and Rous sarcoma virus-transformed chicken embryo cells. Potassium fluxes, ouabain binding, and Na+ and K+ intracellular concentrations were determined for cultures of growing normal, density-inhibited and Rous sarcoma virus-transformed chicken embryo fibroblasts. No significant differences in K+ influx or ouabain binding were detected between growing normal cells and Rous sarcoma virus-transformed cells; however, ouabain binding and ouabain-sensitive K+ influx were 1.5- to 1.8-fold lower in density-inhibited cells. Thus, potassium influx in this system can be classified as a growth-related, but not transformation-specific change. As determined by both flame photometry and radioisotopic (42K) equilibration, growing normal and density-inhibited cells had similar potassium contents, whereas transformed cells exhibited 1.4-fold higher potassium levels. Sodium ion levels, as measured by flame photometry, were also 2- to 4.5-fold higher in transformed than normal or density-inhibited cells. Complementary studies of potassium efflux showed a 1.3- to 1.5-fold higher rate (based on the percentage of pool exiting the cell) in growing normal versus density-inhibited or transformed fibroblasts. Because of the larger potassium pool in transformed cells, efflux based on absolute number of potassium ions is similar in normal and transformed chicken embryo fibroblasts."}
{"id": "PMID:232103", "title": "Periodate oxidation analysis of carbohydrates. XIII. Simultaneous gas chromatographic determination of the aldehydes in the periodate oxidation products of non-dialyzable urinary carbohydrate materials as diethyl dithioacetals.", "content": "The aldehydes in the periodate oxidation products of non-dialyzable urinary carbohydrate materials were determined simultaneously by gas chromatography of their diethyl dithioacetal derivatives. The yields of aldehydes for normal male urine varied considerably among subjects, but their molar ratios were almost constant. The average values for glyceraldehyde/glyoxal and lactaldehyde/glyoxal molar ratios were 0.41 and 0.27, respectively. The average amount of L-fucose at the non-reducing terminals of carbohydrate chains, as estimated from the yield of lactaldehyde, was about 5 mg/day.", "contents": "Periodate oxidation analysis of carbohydrates. XIII. Simultaneous gas chromatographic determination of the aldehydes in the periodate oxidation products of non-dialyzable urinary carbohydrate materials as diethyl dithioacetals. The aldehydes in the periodate oxidation products of non-dialyzable urinary carbohydrate materials were determined simultaneously by gas chromatography of their diethyl dithioacetal derivatives. The yields of aldehydes for normal male urine varied considerably among subjects, but their molar ratios were almost constant. The average values for glyceraldehyde/glyoxal and lactaldehyde/glyoxal molar ratios were 0.41 and 0.27, respectively. The average amount of L-fucose at the non-reducing terminals of carbohydrate chains, as estimated from the yield of lactaldehyde, was about 5 mg/day."}
{"id": "PMID:232114", "title": "Histochemical studies on Raillietina (Raillietina) johri (Cestoda: Davaineidae). II. Nucleoside diphosphatase and thiamine pyrophosphatase.", "content": "Thiamine pyrophosphatase and nucleoside diphosphatase have been studied histochemically in Raillietina (Raillietina) johri. Thiamine pyrophosphatase activity has been observed in the tegument, subtegumental muscle, subtegumental cells, medullary parenchyma, excretory canal and various reproductive structures like testes, ovary, vas deferens, spermatozoa and vitellaria. Eggs exhibit moderate enzyme activity. Various nucleoside diphosphates have been found to be hydrolyzed by thiamine pyrophosphatase. CaCl2, MgCl2 and MnCl2 each activated the enzyme at a final concentration of 6 mM whereas cysteine, reduced glutathione and PCMB inhibited the enzyme activity at a final concentration of 10 mM, 10 mM and 20 mM, respectively. KCN and NaF had no effect on the enzyme staining at concentration as high as 50 mM and 30 mM, respectively. Possible roles of the enzyme in the parasite have been discussed.", "contents": "Histochemical studies on Raillietina (Raillietina) johri (Cestoda: Davaineidae). II. Nucleoside diphosphatase and thiamine pyrophosphatase. Thiamine pyrophosphatase and nucleoside diphosphatase have been studied histochemically in Raillietina (Raillietina) johri. Thiamine pyrophosphatase activity has been observed in the tegument, subtegumental muscle, subtegumental cells, medullary parenchyma, excretory canal and various reproductive structures like testes, ovary, vas deferens, spermatozoa and vitellaria. Eggs exhibit moderate enzyme activity. Various nucleoside diphosphates have been found to be hydrolyzed by thiamine pyrophosphatase. CaCl2, MgCl2 and MnCl2 each activated the enzyme at a final concentration of 6 mM whereas cysteine, reduced glutathione and PCMB inhibited the enzyme activity at a final concentration of 10 mM, 10 mM and 20 mM, respectively. KCN and NaF had no effect on the enzyme staining at concentration as high as 50 mM and 30 mM, respectively. Possible roles of the enzyme in the parasite have been discussed."}
{"id": "PMID:232118", "title": "Cytomegalovirus infection in guinea pigs. III. Persistent viruria, blood transmission, and viral interference.", "content": "Chronic persistent infection with cytomegalovirus (CMV) was studied in random-bred Hartley and inbred strain 2 guinea pigs. Infectious virus was isolated from the urine, kidney, spleen, pancreas, salivary gland, and cervix, but not from buffy coat of persistently infected guinea pigs. Strain 2 animals developed a high rate of chronic viruria, which was not related to isolation of CMV from renal tissue. In female strain 2 guinea pigs viruria was more than twice as prevalent as in males (56% vs. 24%). Transfusion of buffy coat from persistently infected strain 2 animals resulted in CMV infection in both isogenic and allogenic blood recipients, but buffy coat from uninfected donors did not activate CMV in persistently infected isogenic and allogenic blood recipients. Experimental CMV infection of young strain 2 guinea pigs interfered with the expression of guinea pig herpes-like virus, a common endogenous virus in strain 2 animals.", "contents": "Cytomegalovirus infection in guinea pigs. III. Persistent viruria, blood transmission, and viral interference. Chronic persistent infection with cytomegalovirus (CMV) was studied in random-bred Hartley and inbred strain 2 guinea pigs. Infectious virus was isolated from the urine, kidney, spleen, pancreas, salivary gland, and cervix, but not from buffy coat of persistently infected guinea pigs. Strain 2 animals developed a high rate of chronic viruria, which was not related to isolation of CMV from renal tissue. In female strain 2 guinea pigs viruria was more than twice as prevalent as in males (56% vs. 24%). Transfusion of buffy coat from persistently infected strain 2 animals resulted in CMV infection in both isogenic and allogenic blood recipients, but buffy coat from uninfected donors did not activate CMV in persistently infected isogenic and allogenic blood recipients. Experimental CMV infection of young strain 2 guinea pigs interfered with the expression of guinea pig herpes-like virus, a common endogenous virus in strain 2 animals."}
{"id": "PMID:232121", "title": "Quantitative determination of delta 9-tetrahydrocannabinol in cadaver blood.", "content": "We have described a highly sensitive, accurate, and selective method for the determination of delta 9-THC in postmortem blood. Although the method requires the use of fairly complex and sophisticated equipment, the procedure is straightforward and has been reproduced many times in our laboratories. It is thought that this procedure will serve as a useful adjunct to the forensic scientist in his armamentarium for determining physiological levels of important, abused drugs in postmortem analysis.", "contents": "Quantitative determination of delta 9-tetrahydrocannabinol in cadaver blood. We have described a highly sensitive, accurate, and selective method for the determination of delta 9-THC in postmortem blood. Although the method requires the use of fairly complex and sophisticated equipment, the procedure is straightforward and has been reproduced many times in our laboratories. It is thought that this procedure will serve as a useful adjunct to the forensic scientist in his armamentarium for determining physiological levels of important, abused drugs in postmortem analysis."}
{"id": "PMID:232123", "title": "The value of the Duqu\u00e9nois test for cannabis--a survey.", "content": "The Duqu\u00e9nois test is employed throughout the world as part of the identification procedure for cannabis. A survey of results published for more than 400 herbally derived and botanical materials originating from some 270 different plant species is presented. A survey of results from some 200 organic compounds is also presented. The data show that the D-L modification is the most specific. There is no published report of an obviously botanical material, apart from cannabis, that gives a positive D-L test. Apart from cannabinoids, some resorcinol derivatives give a positive test. All of the materials are easily distinguished from cannabis by TLC.", "contents": "The value of the Duqu\u00e9nois test for cannabis--a survey. The Duqu\u00e9nois test is employed throughout the world as part of the identification procedure for cannabis. A survey of results published for more than 400 herbally derived and botanical materials originating from some 270 different plant species is presented. A survey of results from some 200 organic compounds is also presented. The data show that the D-L modification is the most specific. There is no published report of an obviously botanical material, apart from cannabis, that gives a positive D-L test. Apart from cannabinoids, some resorcinol derivatives give a positive test. All of the materials are easily distinguished from cannabis by TLC."}
{"id": "PMID:232124", "title": "The core technique in the determination of age at death of skeletons.", "content": "This study proposed an histological method of estimating age at death in skeletons that uses a 0.4-cm-diameter core of cortical bone. Age-estimating regression equations were generated from data obtained from the analysis of bone cores taken from femurs, tibiae, humeri, and ulnas of cadavers. When the regression equations generated in this study were applied to eight forensic science cases, accurate ages at death were estimated.", "contents": "The core technique in the determination of age at death of skeletons. This study proposed an histological method of estimating age at death in skeletons that uses a 0.4-cm-diameter core of cortical bone. Age-estimating regression equations were generated from data obtained from the analysis of bone cores taken from femurs, tibiae, humeri, and ulnas of cadavers. When the regression equations generated in this study were applied to eight forensic science cases, accurate ages at death were estimated."}
{"id": "PMID:232125", "title": "Variation in the virulence of strains of Mycoplasma pulmonis related to susceptibility to killing by macrophages in vivo.", "content": "The virulence of five strains of Mycoplasma pulmonis, as judged by their ability to survive in the respiratory tract and induce pneumonia in CBA mice, was related to the ability of viable organisms to persist in the peritoneal cavity. This appeared to be the result of differences in the ability of the strains to resist killing by peritoneal macrophages in vivo. It is suggested that resistance to phagocytosis by macrophages is an important determinant of virulence for M. pulmonis.", "contents": "Variation in the virulence of strains of Mycoplasma pulmonis related to susceptibility to killing by macrophages in vivo. The virulence of five strains of Mycoplasma pulmonis, as judged by their ability to survive in the respiratory tract and induce pneumonia in CBA mice, was related to the ability of viable organisms to persist in the peritoneal cavity. This appeared to be the result of differences in the ability of the strains to resist killing by peritoneal macrophages in vivo. It is suggested that resistance to phagocytosis by macrophages is an important determinant of virulence for M. pulmonis."}
{"id": "PMID:232126", "title": "Isolation and partial characterization of four plasmids from antibiotic-resistant thermophilic bacilli.", "content": "Twenty-nine antibiotic-resistant isolates of thermophilic bacilli were examined for the presence of covalently closed circular duplex DNA molecules by agarose-gel electrophoresis and caesium chloride-ethidium bromide density gradient centrifugation. Five of the 29 strains tested contained covalently closed circular molecules. Two of the streptomycin-resistant strains contained the same two plasmids: pAB118A of molecular weight 4.9 X 10(6) (7.0 kilobases) and pAB118B of molecular weight 3.0 X 10(6) (4.3 kilobases). Two of the tetracycline-resistant strains each contained a plasmid (pAB124) of molecular weight 2.9 X 10(6) (4.14 kilobases), while a third harboured a small plasmid (pAB128) of molecular weight 2.5 X 10(6) (3.57 kilobases). These plasmids were digested with 19 different restriction endonucleases and the numbers of cleavage sites were determined. Transformation of Bacillus subtilis (168 (Trp-) with purified plasmid DNA indicated that pAB124 conferred tetracycline resistance on the host.", "contents": "Isolation and partial characterization of four plasmids from antibiotic-resistant thermophilic bacilli. Twenty-nine antibiotic-resistant isolates of thermophilic bacilli were examined for the presence of covalently closed circular duplex DNA molecules by agarose-gel electrophoresis and caesium chloride-ethidium bromide density gradient centrifugation. Five of the 29 strains tested contained covalently closed circular molecules. Two of the streptomycin-resistant strains contained the same two plasmids: pAB118A of molecular weight 4.9 X 10(6) (7.0 kilobases) and pAB118B of molecular weight 3.0 X 10(6) (4.3 kilobases). Two of the tetracycline-resistant strains each contained a plasmid (pAB124) of molecular weight 2.9 X 10(6) (4.14 kilobases), while a third harboured a small plasmid (pAB128) of molecular weight 2.5 X 10(6) (3.57 kilobases). These plasmids were digested with 19 different restriction endonucleases and the numbers of cleavage sites were determined. Transformation of Bacillus subtilis (168 (Trp-) with purified plasmid DNA indicated that pAB124 conferred tetracycline resistance on the host."}
{"id": "PMID:232127", "title": "The ecology of gonococcal plasmids.", "content": "Of 261 strains of Neisseria gonorrhoeae examined for plasmids, 6 were plasmid-free, 217 contained only a small multicopy 2.6 X 10(6) dalton plasmid and 38 carried a large 24.5 X 10(6) dalton plasmid. Restriction enzyme digests and DNA-DNA hybridization studies revealed that the large plasmids isolated between 1940 and 1978 share a common core of DNA sequences (70 to 100%) and represent a group of closely related molecules.", "contents": "The ecology of gonococcal plasmids. Of 261 strains of Neisseria gonorrhoeae examined for plasmids, 6 were plasmid-free, 217 contained only a small multicopy 2.6 X 10(6) dalton plasmid and 38 carried a large 24.5 X 10(6) dalton plasmid. Restriction enzyme digests and DNA-DNA hybridization studies revealed that the large plasmids isolated between 1940 and 1978 share a common core of DNA sequences (70 to 100%) and represent a group of closely related molecules."}
{"id": "PMID:232128", "title": "Intracellular state of Epstein-Barr virus DNA in producer cell lines.", "content": "The physical state of the Epstein-Barr virus (EBV) DNA in three cell lines which spontaneously produce virus has been characterized. Circular EBV DNA molecules have been found in P3HR-I, B95-8 and M8I cells. The size of the intracellular M8I circular EBV DNA molecules is comparable with the linear virus genome isolated from virus particles but the circular P3HR-I and B95-8 DNA molecules are shorter than the virion DNA . In addition to the circular form, some EBV DNA with physical properties indicative of integrated sequences was found in all three producer cell lines. There was no marked change in the amount of either the circular or integrated forms of EBV DNA when these producer cell lines were grown in the presence of phosphonacetic acid to suppress the spontaneous virus production which occurs in a small percentage of the cells in untreated cultures.", "contents": "Intracellular state of Epstein-Barr virus DNA in producer cell lines. The physical state of the Epstein-Barr virus (EBV) DNA in three cell lines which spontaneously produce virus has been characterized. Circular EBV DNA molecules have been found in P3HR-I, B95-8 and M8I cells. The size of the intracellular M8I circular EBV DNA molecules is comparable with the linear virus genome isolated from virus particles but the circular P3HR-I and B95-8 DNA molecules are shorter than the virion DNA . In addition to the circular form, some EBV DNA with physical properties indicative of integrated sequences was found in all three producer cell lines. There was no marked change in the amount of either the circular or integrated forms of EBV DNA when these producer cell lines were grown in the presence of phosphonacetic acid to suppress the spontaneous virus production which occurs in a small percentage of the cells in untreated cultures."}
{"id": "PMID:232129", "title": "Molecular relationship of the DNA and RNA of intracytoplasmic A particles to mouse and mammary tumour virus genomes.", "content": "We have directly tested the hypothesis that single-stranded cytoplasmic A particle-associated DNA (ss CAP DNA) is a murine mammary tumour virus (MMTV) proviral intermediate by hybridizing 125I-labelled ss CAP DNA to MMTV RNA or to MMTV complementary DNA (cDNA). 125I-labelled CAP DNA did not form duplexes with either MMTV RNA or MMTV cDNA. In contrast, CAP RNA hybridized readily with MMTV cDNA. CAP RNA contained all the MMTV virus sequences, but at lower concentrations than in MMTV virus particles. Single-stranded CAP DNA hybridized readily with mouse DNA from several sources. A study of the rate of hybridization of CAP DNA to cell DNA at various driver to probe ratios showed that its rate of hybridization is similar to that of tumour cell DNA reassociation. Further, in reassociation studies accelerated by using the phenol emulsion reassociation technique (PERT), CAP DNA originally isolated as single-stranded DNA was shown to reanneal (70%), to protect 125I-cell DNA to the same extent (67%) and to do so with kinetics of reassociation equivalent to that of mouse DNA. Although CAP DNA isolates were slightly enriched for MMTV specific sequences when compared to total cellular DNA, we conclude that the majority of ss CAP-associated DNA is equivalent to a random sample of total tumour cell DNA.", "contents": "Molecular relationship of the DNA and RNA of intracytoplasmic A particles to mouse and mammary tumour virus genomes. We have directly tested the hypothesis that single-stranded cytoplasmic A particle-associated DNA (ss CAP DNA) is a murine mammary tumour virus (MMTV) proviral intermediate by hybridizing 125I-labelled ss CAP DNA to MMTV RNA or to MMTV complementary DNA (cDNA). 125I-labelled CAP DNA did not form duplexes with either MMTV RNA or MMTV cDNA. In contrast, CAP RNA hybridized readily with MMTV cDNA. CAP RNA contained all the MMTV virus sequences, but at lower concentrations than in MMTV virus particles. Single-stranded CAP DNA hybridized readily with mouse DNA from several sources. A study of the rate of hybridization of CAP DNA to cell DNA at various driver to probe ratios showed that its rate of hybridization is similar to that of tumour cell DNA reassociation. Further, in reassociation studies accelerated by using the phenol emulsion reassociation technique (PERT), CAP DNA originally isolated as single-stranded DNA was shown to reanneal (70%), to protect 125I-cell DNA to the same extent (67%) and to do so with kinetics of reassociation equivalent to that of mouse DNA. Although CAP DNA isolates were slightly enriched for MMTV specific sequences when compared to total cellular DNA, we conclude that the majority of ss CAP-associated DNA is equivalent to a random sample of total tumour cell DNA."}
{"id": "PMID:232130", "title": "Phosphorylation of a ribosomal protein and of virus-specific proteins in cells infected with herpes simplex virus.", "content": "In cells infected with herpes simplex virus a protein associated with the small subunit of ribosomes became phosphorylated. It was not detectably labelled with 14C-amino acids added after infection and is therefore probably a cellular protein. The phosphorylated ribosomal proteins from HSV-1- and HSV-2-infected cells were indistinguishable electrophoretically and had an apparent mol. wt. of about 48 000. Phosphorylation of the 48K protein was detected 2 to 3 h after infection and reached a maximum rate at 4 to 5 h. It was prevented by adding cycloheximide at 2 h, or actinomycin at 1.5 h p.i., or azetidine at the beginning of infection. The phosphorylation did not occur on reversal of a cycloheximide block in the presence of actinomycin, confirming that it is not caused by a virus alpha-polypeptide. Virus that had been irradiated with u.v. light, although still able to suppress synthesis of cellular protein and DNA, did not induce phosphorylation of the 48K ribosomal protein. Therefore the phosphorylation is not responsible for the suppression of host synthesis. The alpha polypeptides ICP 4, 0, 22 and 27 are also phosphorylated but, in contrast to that of the ribosomal protein, their phosphorylation does not depend on the synthesis of beta and gamma polypeptides. It is probably mediated by a host enzyme.", "contents": "Phosphorylation of a ribosomal protein and of virus-specific proteins in cells infected with herpes simplex virus. In cells infected with herpes simplex virus a protein associated with the small subunit of ribosomes became phosphorylated. It was not detectably labelled with 14C-amino acids added after infection and is therefore probably a cellular protein. The phosphorylated ribosomal proteins from HSV-1- and HSV-2-infected cells were indistinguishable electrophoretically and had an apparent mol. wt. of about 48 000. Phosphorylation of the 48K protein was detected 2 to 3 h after infection and reached a maximum rate at 4 to 5 h. It was prevented by adding cycloheximide at 2 h, or actinomycin at 1.5 h p.i., or azetidine at the beginning of infection. The phosphorylation did not occur on reversal of a cycloheximide block in the presence of actinomycin, confirming that it is not caused by a virus alpha-polypeptide. Virus that had been irradiated with u.v. light, although still able to suppress synthesis of cellular protein and DNA, did not induce phosphorylation of the 48K ribosomal protein. Therefore the phosphorylation is not responsible for the suppression of host synthesis. The alpha polypeptides ICP 4, 0, 22 and 27 are also phosphorylated but, in contrast to that of the ribosomal protein, their phosphorylation does not depend on the synthesis of beta and gamma polypeptides. It is probably mediated by a host enzyme."}
{"id": "PMID:232131", "title": "Complementation with ts mutants of herpes simplex virus.", "content": "Tests to detect complementation between ts mutants of herpes simplex virus types 1 and 2 infectious centre and yield of virus assay were investigated. Progeny analysis of both intratypic and intertypic complementation showed a considerable proportion of recombinant or ts+ virus in the progeny; this was more marked in the infectious centre tests. Virus of intermediate temperature-sensitivity was produced in intratypic as well as intertypic complementation. Reduction in the input multiplicity of one of the two mutants in the test to extremely low levels did not prevent complementation, suggesting that non-infectious particles probably contribute to complementation. Demonstration of virus DNA synthesis in mixedly-infected cells at the non-permissive temperature was used to detect complementation between DNA-negative mutants.", "contents": "Complementation with ts mutants of herpes simplex virus. Tests to detect complementation between ts mutants of herpes simplex virus types 1 and 2 infectious centre and yield of virus assay were investigated. Progeny analysis of both intratypic and intertypic complementation showed a considerable proportion of recombinant or ts+ virus in the progeny; this was more marked in the infectious centre tests. Virus of intermediate temperature-sensitivity was produced in intratypic as well as intertypic complementation. Reduction in the input multiplicity of one of the two mutants in the test to extremely low levels did not prevent complementation, suggesting that non-infectious particles probably contribute to complementation. Demonstration of virus DNA synthesis in mixedly-infected cells at the non-permissive temperature was used to detect complementation between DNA-negative mutants."}
{"id": "PMID:232132", "title": "The serological relationship of varicella-zoster virus to other primate herpesviruses.", "content": "The serological relationship between viruses producing varicella-like exanthems in several subhuman primates, varicella-zoster virus (VZV) and herpes simplex viruses (HSV) types 1 and 2, was investigated. All the primate viruses were related to VZV and some to HSV also. These results show that there is a group of varicella viruses, comprising four distinct entities, some of which may be useful for the establishment of an animal model for varicella.", "contents": "The serological relationship of varicella-zoster virus to other primate herpesviruses. The serological relationship between viruses producing varicella-like exanthems in several subhuman primates, varicella-zoster virus (VZV) and herpes simplex viruses (HSV) types 1 and 2, was investigated. All the primate viruses were related to VZV and some to HSV also. These results show that there is a group of varicella viruses, comprising four distinct entities, some of which may be useful for the establishment of an animal model for varicella."}
{"id": "PMID:232133", "title": "Virus-specific DNA sequences present in cells which carry the herpes simplex virus thymidine kinase gene.", "content": "Two independently derived cell lines which carry the herpes simplex type 2 thymidine kinase gene have been examined for the presence of HSV-2-specific DNA sequences. Both cell lines contained 1 to 3 copies per cell of a sequence lying within map co-ordinates 0.2 to 0.4 of the HSV-2 genome. Revertant cells, which contained no detectable thymidine kinase, did not contain this DNA sequence. The failure of EcoR1-restricted HSV-2 DNA to act as a donor of the thymidine kinase gene in transformation experiments suggests that the gene lies close to the EcoR1 restriction site within this sequence at a map position of approx. 0.3. The HSV-2 kinase gene is therefore approximately co-linear with the HSV-1 gene.", "contents": "Virus-specific DNA sequences present in cells which carry the herpes simplex virus thymidine kinase gene. Two independently derived cell lines which carry the herpes simplex type 2 thymidine kinase gene have been examined for the presence of HSV-2-specific DNA sequences. Both cell lines contained 1 to 3 copies per cell of a sequence lying within map co-ordinates 0.2 to 0.4 of the HSV-2 genome. Revertant cells, which contained no detectable thymidine kinase, did not contain this DNA sequence. The failure of EcoR1-restricted HSV-2 DNA to act as a donor of the thymidine kinase gene in transformation experiments suggests that the gene lies close to the EcoR1 restriction site within this sequence at a map position of approx. 0.3. The HSV-2 kinase gene is therefore approximately co-linear with the HSV-1 gene."}
{"id": "PMID:232134", "title": "Purification and identification of the RNA-dependent RNA polymerase of foot-and-mouth disease virus.", "content": "The RNA-dependent RNA polymerase induced in BHK 21 cells by infection with foot-and-mouth disease virus has been isolated from the replication complex. It contains a major, virus-coded protein with mol. wt. 56 000 which appears from serological studies and tryptic peptide mapping to be the same as the virus infection associated (VIA) antigen and the protein P56 found in cells infected with the virus. Other virus coded proteins and a host cell protein were present in the partially purified replication complex but were removed by digestion with ribonuclease T1, leaving only the major virus coded protein. The tryptic peptide maps of the VIA antigen of the seven serotypes of the virus were similar, suggesting a high level of conservation in that region of the genome coding for the RNA polymerase of each type.", "contents": "Purification and identification of the RNA-dependent RNA polymerase of foot-and-mouth disease virus. The RNA-dependent RNA polymerase induced in BHK 21 cells by infection with foot-and-mouth disease virus has been isolated from the replication complex. It contains a major, virus-coded protein with mol. wt. 56 000 which appears from serological studies and tryptic peptide mapping to be the same as the virus infection associated (VIA) antigen and the protein P56 found in cells infected with the virus. Other virus coded proteins and a host cell protein were present in the partially purified replication complex but were removed by digestion with ribonuclease T1, leaving only the major virus coded protein. The tryptic peptide maps of the VIA antigen of the seven serotypes of the virus were similar, suggesting a high level of conservation in that region of the genome coding for the RNA polymerase of each type."}
{"id": "PMID:232135", "title": "Quantitative electron microscopy of intracytoplasmic type A particles at kinetochores of metaphase chromosomes isolated from Chinese hamster and murine cell lines.", "content": "We have successfully isolated and spread individual chromosomes of CHO-KI cells for electron microscopic karyotyping. Controlled preparation permitted a quantitative evaluation of the association between endogenous intracytoplasmic type A virus precursor particles and the centromeric region (kinetochores) of isolated chromosomes at prophase and metaphase. Our results suggest the transfer of type A particles from the cytoplasmic to the centromeric regions during early metaphase in conjunction with microtubule assembly at a time when the kinetochores are structurally mature and capable of binding microtubules. Preliminary comparable studies of the endogenous M432 virus propagated in murine cells support these findings. Our results are discussed with respect to mechanisms of intracellular movement of virus precursor particles and the interference with components of both the cytoskeleton and the mitotic apparatus.", "contents": "Quantitative electron microscopy of intracytoplasmic type A particles at kinetochores of metaphase chromosomes isolated from Chinese hamster and murine cell lines. We have successfully isolated and spread individual chromosomes of CHO-KI cells for electron microscopic karyotyping. Controlled preparation permitted a quantitative evaluation of the association between endogenous intracytoplasmic type A virus precursor particles and the centromeric region (kinetochores) of isolated chromosomes at prophase and metaphase. Our results suggest the transfer of type A particles from the cytoplasmic to the centromeric regions during early metaphase in conjunction with microtubule assembly at a time when the kinetochores are structurally mature and capable of binding microtubules. Preliminary comparable studies of the endogenous M432 virus propagated in murine cells support these findings. Our results are discussed with respect to mechanisms of intracellular movement of virus precursor particles and the interference with components of both the cytoskeleton and the mitotic apparatus."}
{"id": "PMID:232136", "title": "Evidence for secondary structure in poliovirus virion RNA demonstrated by antibodies against double-stranded RNA.", "content": "Poliovirus particle RNA has been considered to have little secondary structure. Specific binding of poliovirion RNA by antibodies against double-stranded RNA (dsRNA) has been confirmed and further characterized by a radioimmunoassay using Staphylococcus aureus protein A to precipitate the nucleic acid-antibody complex. Competitive binding studies between virion single-stranded RNA (ssRNA) and poly(I).poly(C) demonstrated that the dsRNA effectively inhibited binding of radiolabelled poliovirion RNA by the anti-dsRNA antibodies but the virion RNA was a poor competitor of radiolabelled ds RNA. This indicates that both RNAs reacted with the same species of antibodies in the sera, but avidity of the antibodies for dsRNA was greater than for the poliovirion RNA.", "contents": "Evidence for secondary structure in poliovirus virion RNA demonstrated by antibodies against double-stranded RNA. Poliovirus particle RNA has been considered to have little secondary structure. Specific binding of poliovirion RNA by antibodies against double-stranded RNA (dsRNA) has been confirmed and further characterized by a radioimmunoassay using Staphylococcus aureus protein A to precipitate the nucleic acid-antibody complex. Competitive binding studies between virion single-stranded RNA (ssRNA) and poly(I).poly(C) demonstrated that the dsRNA effectively inhibited binding of radiolabelled poliovirion RNA by the anti-dsRNA antibodies but the virion RNA was a poor competitor of radiolabelled ds RNA. This indicates that both RNAs reacted with the same species of antibodies in the sera, but avidity of the antibodies for dsRNA was greater than for the poliovirion RNA."}
{"id": "PMID:232137", "title": "Conservation and variation in Orthopoxvirus genome structure.", "content": "Orthopoxvirus DNA from representative strains of rabbitpox, vaccinia, monkeypox, variola, cowpox and ectromelia viruses was analysed by cleavage with restriction endonucleases HindIII, XhoI or SmaI. Genome mol. wt. vary from about 120 x 10(6) for rabbitpox to about 145 x 10(6) for cowpox. Physical maps of cleavage sites are similar and characteristic for strains of the same Orthopoxvirus type. The distribution of HindIII sites suggests that an internal region of mol. wt. about 30 x 10(6) is highly conserved between Orthopoxvirus genomes although some type-specific differences occur within this region, especially with strains of ectromelia virus. Conservation of internal sequences is less marked following analysis with XhoI although cleavages within this central region of particular genomes appear to represent a subset of preferred sites. Endonuclease SmaI cleaves exceptionally infrequently and distinguishes variola, monkeypox, vaccinia, cowpox or ectromelia viruses. Type specific differences result largely from extensive, near terminal variations in length and sequence. Representative Orthopoxvirus genomes have rapidly renaturing terminal restriction fragments confirming the presence of near terminal, covalent cross-links. Terminal restriction fragments from the same or different genomes generally cross hybridize indicating the presence of near terminal repetitions of mol. wt. up to 6 x 10(6) and which share at least a subset of common sequences. Variola strains however, appear to lack such sequences from one specific terminus which maps shorter than that of related viruses.", "contents": "Conservation and variation in Orthopoxvirus genome structure. Orthopoxvirus DNA from representative strains of rabbitpox, vaccinia, monkeypox, variola, cowpox and ectromelia viruses was analysed by cleavage with restriction endonucleases HindIII, XhoI or SmaI. Genome mol. wt. vary from about 120 x 10(6) for rabbitpox to about 145 x 10(6) for cowpox. Physical maps of cleavage sites are similar and characteristic for strains of the same Orthopoxvirus type. The distribution of HindIII sites suggests that an internal region of mol. wt. about 30 x 10(6) is highly conserved between Orthopoxvirus genomes although some type-specific differences occur within this region, especially with strains of ectromelia virus. Conservation of internal sequences is less marked following analysis with XhoI although cleavages within this central region of particular genomes appear to represent a subset of preferred sites. Endonuclease SmaI cleaves exceptionally infrequently and distinguishes variola, monkeypox, vaccinia, cowpox or ectromelia viruses. Type specific differences result largely from extensive, near terminal variations in length and sequence. Representative Orthopoxvirus genomes have rapidly renaturing terminal restriction fragments confirming the presence of near terminal, covalent cross-links. Terminal restriction fragments from the same or different genomes generally cross hybridize indicating the presence of near terminal repetitions of mol. wt. up to 6 x 10(6) and which share at least a subset of common sequences. Variola strains however, appear to lack such sequences from one specific terminus which maps shorter than that of related viruses."}
{"id": "PMID:232138", "title": "Cellular basis for susceptibility to mouse cytomegalovirus: evidence from tracheal organ culture.", "content": "Tracheal organ cultures were prepared from strains of mice with known susceptibility to the lethal effects of mouse cytomegalovirus. When organ cultures from susceptible mice were infected with this virus, characteristic c.p.e. developed and virus titres greater than 10(5) p.f.u./ml were produced 2 to 3 weeks after infection. Identically infected tracheal organ cultures from resistant mice consistently failed to develop significant virus c.p.e. and produced 10- to 100-fold lower titres of virus. When fibroblast cultures were infected with mouse cytomegalovirus, however, no consistent differences between susceptible and resistant mouse strains were observed. Since cytomegalovirus replicates in epithelial cells both in vivo and in tracheal organ culture, these results suggest that resistance may be based in part upon innate genetic susceptibility of epithelial cells to cytomegalovirus infection.", "contents": "Cellular basis for susceptibility to mouse cytomegalovirus: evidence from tracheal organ culture. Tracheal organ cultures were prepared from strains of mice with known susceptibility to the lethal effects of mouse cytomegalovirus. When organ cultures from susceptible mice were infected with this virus, characteristic c.p.e. developed and virus titres greater than 10(5) p.f.u./ml were produced 2 to 3 weeks after infection. Identically infected tracheal organ cultures from resistant mice consistently failed to develop significant virus c.p.e. and produced 10- to 100-fold lower titres of virus. When fibroblast cultures were infected with mouse cytomegalovirus, however, no consistent differences between susceptible and resistant mouse strains were observed. Since cytomegalovirus replicates in epithelial cells both in vivo and in tracheal organ culture, these results suggest that resistance may be based in part upon innate genetic susceptibility of epithelial cells to cytomegalovirus infection."}
{"id": "PMID:232139", "title": "Activation of the endogenous proviral genes in mouse cells is not followed by increased sensitivity to deoxyribonuclease I digestion.", "content": "The disposition of chromosome proteins about the endogenous proviral DNA of BALB-c mouse has been studied. The sensitivity of the endogenous proviral DNA sequences to deoxyribonuclease I (DNaseI) was analysed in BALB-c mouse tissues (liver and spleen) and in the cell line JLS-V9 which does not produce virus. On all of these preparations the endogenous proviral DNA was as sensitive to DNase I digestion as total chromatin. Since the proviral genes in JLS-V9 cells were silent, it was of interest to study possible changes in the chromatin structure following virus induction by iododeoxyuridine. We could not detect any increase in the sensitivity of the endogenous proviral DNA to DNase I digestion following induction. The induction was very efficient, however, since 60% of the cells responded to produce intracellular virus antigens.", "contents": "Activation of the endogenous proviral genes in mouse cells is not followed by increased sensitivity to deoxyribonuclease I digestion. The disposition of chromosome proteins about the endogenous proviral DNA of BALB-c mouse has been studied. The sensitivity of the endogenous proviral DNA sequences to deoxyribonuclease I (DNaseI) was analysed in BALB-c mouse tissues (liver and spleen) and in the cell line JLS-V9 which does not produce virus. On all of these preparations the endogenous proviral DNA was as sensitive to DNase I digestion as total chromatin. Since the proviral genes in JLS-V9 cells were silent, it was of interest to study possible changes in the chromatin structure following virus induction by iododeoxyuridine. We could not detect any increase in the sensitivity of the endogenous proviral DNA to DNase I digestion following induction. The induction was very efficient, however, since 60% of the cells responded to produce intracellular virus antigens."}
{"id": "PMID:232140", "title": "An outbreak of gastroenteritis associated with calicivirus in an infant home.", "content": "In October 1977 an outbreak of acute infectious diarrhea occurred in an infant home in the city of Sapporo, Japan. Of 34 residents aged two to 20 months, 26 (77%) suffered from diarrhea. In ten of these patients the diarrhea was accompanied by vomiting. Electron microscopic examinations revealed typical calicivirus particles in eight faecal specimens, seven of which were from the group of 26 affected patients (28%) and one of which was from the group of eight infants without symptoms (13%). Immune electron microscopy tests for antibody responses against one of the isolated strains of calicivirus were carried out on 27 paired pre- and post-outbreak sera. Seroconversions were demonstrated in 18 of 19 (95%) affected infants and in six of eight (75%) unaffected infants. One patient with lack of antibody response was the youngest child--two months old. Periodic surveys on enteric viruses circulating in the home revealed that calicivirus was specifically associated with the outbreak of gastroenteritis. These observations provide further evidence for the causative role of calicivirus in acute gastroenteritis in children.", "contents": "An outbreak of gastroenteritis associated with calicivirus in an infant home. In October 1977 an outbreak of acute infectious diarrhea occurred in an infant home in the city of Sapporo, Japan. Of 34 residents aged two to 20 months, 26 (77%) suffered from diarrhea. In ten of these patients the diarrhea was accompanied by vomiting. Electron microscopic examinations revealed typical calicivirus particles in eight faecal specimens, seven of which were from the group of 26 affected patients (28%) and one of which was from the group of eight infants without symptoms (13%). Immune electron microscopy tests for antibody responses against one of the isolated strains of calicivirus were carried out on 27 paired pre- and post-outbreak sera. Seroconversions were demonstrated in 18 of 19 (95%) affected infants and in six of eight (75%) unaffected infants. One patient with lack of antibody response was the youngest child--two months old. Periodic surveys on enteric viruses circulating in the home revealed that calicivirus was specifically associated with the outbreak of gastroenteritis. These observations provide further evidence for the causative role of calicivirus in acute gastroenteritis in children."}
{"id": "PMID:232141", "title": "Comparison of four-layer radioimmunoassay and electron microscopy for detection of human rotavirus.", "content": "A four-layer radioimmunoassay (RIA) using polystyrene beads as the solid phase, anti-rota guinea pig IgG as primary antibody, anti-rota rabbit IgG as secondary antibody, and 125I-labelled sheep anti-rabbit immunoglobulin as indicator antibody has been developed for the detection of human rotavirus in stool specimens. A comparison was made of the developed RIA, routine electron microscopy, and research electron microscopy of 147 unconcentrated stool specimens from patients with infantile gastroenteritis. In routine electron microscopy 17 (11.6%) false-positive or false-negative results were obtained when compared with research electron microscopy. Each specimen positive in research electron microscopy was positive in RIA, and six additional RIA positives were found from 58 electron microscopy negative specimens. A confirmatory test was necessary to find out marginally positive but nonspecific reactions in RIA. The developed radioimmunoassay is slightly more sensitive than research electron microscopy of unconcentrated stool specimens and considerably more sensitive and more specific than routine electron microscopy.", "contents": "Comparison of four-layer radioimmunoassay and electron microscopy for detection of human rotavirus. A four-layer radioimmunoassay (RIA) using polystyrene beads as the solid phase, anti-rota guinea pig IgG as primary antibody, anti-rota rabbit IgG as secondary antibody, and 125I-labelled sheep anti-rabbit immunoglobulin as indicator antibody has been developed for the detection of human rotavirus in stool specimens. A comparison was made of the developed RIA, routine electron microscopy, and research electron microscopy of 147 unconcentrated stool specimens from patients with infantile gastroenteritis. In routine electron microscopy 17 (11.6%) false-positive or false-negative results were obtained when compared with research electron microscopy. Each specimen positive in research electron microscopy was positive in RIA, and six additional RIA positives were found from 58 electron microscopy negative specimens. A confirmatory test was necessary to find out marginally positive but nonspecific reactions in RIA. The developed radioimmunoassay is slightly more sensitive than research electron microscopy of unconcentrated stool specimens and considerably more sensitive and more specific than routine electron microscopy."}
{"id": "PMID:232142", "title": "Replication of murine cytomegalovirus in murine Y-1 cells.", "content": "Murine Y-1 cells, a continuous epithelial cell line derived from an adrenal adenocarcinoma, are highly susceptible to murine cytomegalovirus (MCMV) infection. Inoculation of these cells with MCMV results in production of infectious virus and is associated with development of both cytopathic changes and the expression of viral-specific nuclear and cytoplasmic antigens. Examination of the ultrastructure of infected Y-1 cells reveals MCMV in various stages of replication. Cytomegalovirus replication in this hormone-responsive epithelial cell line should provide a model system in which virus--host cell interactions and their effects on cellular metabolism can be studied.", "contents": "Replication of murine cytomegalovirus in murine Y-1 cells. Murine Y-1 cells, a continuous epithelial cell line derived from an adrenal adenocarcinoma, are highly susceptible to murine cytomegalovirus (MCMV) infection. Inoculation of these cells with MCMV results in production of infectious virus and is associated with development of both cytopathic changes and the expression of viral-specific nuclear and cytoplasmic antigens. Examination of the ultrastructure of infected Y-1 cells reveals MCMV in various stages of replication. Cytomegalovirus replication in this hormone-responsive epithelial cell line should provide a model system in which virus--host cell interactions and their effects on cellular metabolism can be studied."}
{"id": "PMID:232143", "title": "The effect of sodium thiocyanate on virus structure.", "content": "A study of two different virus types after elution from immunosorbent columns by sodium thiocyanate has shown that virus degradation occurs. The two virus types studied were hepatitis B and rotavirus. Hepatitis B antigen (HBAg) was only slowly degraded and retained many of its morphological features, although in an altered form; rotavirus was highly sensitive to the chaotropic agent, losing both its viability and its morphological integrity. During the process of disassembly a previously undetected inner component of rotavirus could be visualised, which was termed the \"core.\"", "contents": "The effect of sodium thiocyanate on virus structure. A study of two different virus types after elution from immunosorbent columns by sodium thiocyanate has shown that virus degradation occurs. The two virus types studied were hepatitis B and rotavirus. Hepatitis B antigen (HBAg) was only slowly degraded and retained many of its morphological features, although in an altered form; rotavirus was highly sensitive to the chaotropic agent, losing both its viability and its morphological integrity. During the process of disassembly a previously undetected inner component of rotavirus could be visualised, which was termed the \"core.\""}
{"id": "PMID:232144", "title": "Purification of poliovirus by affinity chromatography.", "content": "Poliovirus type 1 (Mahoney strain) has been purified by retention on a Sepharose 4B-antibody column and elution with 3M K thiocyanate. The virus was recovered in excellent yield and its purity was as high as that achieved by detergent treatment followed by sucrose gradient centrifugation. The column could be re-used and its capacity was sufficiently high to make it a useful method for the purification of milligram quantities of the virus.", "contents": "Purification of poliovirus by affinity chromatography. Poliovirus type 1 (Mahoney strain) has been purified by retention on a Sepharose 4B-antibody column and elution with 3M K thiocyanate. The virus was recovered in excellent yield and its purity was as high as that achieved by detergent treatment followed by sucrose gradient centrifugation. The column could be re-used and its capacity was sufficiently high to make it a useful method for the purification of milligram quantities of the virus."}
{"id": "PMID:232145", "title": "The occurrence of calicivirus in infants with acute gastroenteritis.", "content": "Calicivirus was detected in 8 (1.2%) of 647 hospitalized patients during a survey of acute gastroenteritis in infants and young children, conducted between December 1974 and September 1977. Morphologically calicivirus was approximately 30 nm in diameter with an easily recognizable staining \"star of David\" configuration. Its buoyant density in cesium chloride was 1.38-1.40 gm/ml. The serologic response to calicivirus by immune electron microscopy (IEM) was demonstrated only in paired sera from patients who shed the virus in their stools. The results suggest that calicivirus might be a cause of acute gastroenteritis in infants and young children.", "contents": "The occurrence of calicivirus in infants with acute gastroenteritis. Calicivirus was detected in 8 (1.2%) of 647 hospitalized patients during a survey of acute gastroenteritis in infants and young children, conducted between December 1974 and September 1977. Morphologically calicivirus was approximately 30 nm in diameter with an easily recognizable staining \"star of David\" configuration. Its buoyant density in cesium chloride was 1.38-1.40 gm/ml. The serologic response to calicivirus by immune electron microscopy (IEM) was demonstrated only in paired sera from patients who shed the virus in their stools. The results suggest that calicivirus might be a cause of acute gastroenteritis in infants and young children."}
{"id": "PMID:232146", "title": "Evaluation of bone-marrow scanning with technetium-99m sulfur colloid in pediatric oncology.", "content": "Eighty-six technetium-99m sulfur colloid (Tc-SC) bone-marrow scans in 56 pediatric oncology patients were reviewed. The distribution of the sulfur colloid was similar to that in adult bone marrow in normal children older than 10 yr, and involved progressively more marrow of the extremities in normal children under 10 years of age. After irradiation or chemotherapy there was an extension of the Tc-SC to peripheral marrow sites. There was also diminished uptake of the tracer in sites corresponding to irradiated areas. In most patients there was recovery of these defects by 6 mo after completion of therapy. Tumor replacement of the marrow was reflected in the scans, and the extent of the scan defect paralleled the course of the disease. In four patients, despite normal bone scans and radiographs, marrow-scan abnormalities due to tumor replacement were present and confirmed by needle aspiration and/or biopsy. In two other patients, the marrow-scan abnormality preceded radiographic and histologic evidence of tumor metastasis. Two patients who responded clinically showed persistent defects; biopsy in one revealed fibrosis. Technetium-99m sulfur colloid bone-marrow scanning appears to be a sensitive monitor of marrow alteration caused by metastases, irradiation damage, or tissue fibrosis in children receiving treatment for cancer.", "contents": "Evaluation of bone-marrow scanning with technetium-99m sulfur colloid in pediatric oncology. Eighty-six technetium-99m sulfur colloid (Tc-SC) bone-marrow scans in 56 pediatric oncology patients were reviewed. The distribution of the sulfur colloid was similar to that in adult bone marrow in normal children older than 10 yr, and involved progressively more marrow of the extremities in normal children under 10 years of age. After irradiation or chemotherapy there was an extension of the Tc-SC to peripheral marrow sites. There was also diminished uptake of the tracer in sites corresponding to irradiated areas. In most patients there was recovery of these defects by 6 mo after completion of therapy. Tumor replacement of the marrow was reflected in the scans, and the extent of the scan defect paralleled the course of the disease. In four patients, despite normal bone scans and radiographs, marrow-scan abnormalities due to tumor replacement were present and confirmed by needle aspiration and/or biopsy. In two other patients, the marrow-scan abnormality preceded radiographic and histologic evidence of tumor metastasis. Two patients who responded clinically showed persistent defects; biopsy in one revealed fibrosis. Technetium-99m sulfur colloid bone-marrow scanning appears to be a sensitive monitor of marrow alteration caused by metastases, irradiation damage, or tissue fibrosis in children receiving treatment for cancer."}
{"id": "PMID:232147", "title": "Comparison of Tc-99m pyrophosphate and Tc-99m methylene diphosphonate in acute myocardial infarction: concise communication.", "content": "This study compared Tc-99m pyrophosphate (PPi) and Tc-99m methylene diphosphonate (MDP) for myocardial infarct imaging in 24 patients with diagnosed acute myocardial infarction. The radiopharmaceuticals were administered randomly and interpreted without knowledge of the sequence used. Twenty-three patients (96%) had positive Tc-99m PPi scintigrams, but only 17 (71%) had a positive Tc-99m MDP study (P less than 0.05). In addition, a comparison of the relative intensity with each agent revealed greater intensity with Tc-99m in 21 cases, equal intensity in two cases, and less intensity in only one case (p less than 0.001). These findings support the superiority of Tc-99m PPi as the agent of choice for myocardial scintigraphy in acute infarction.", "contents": "Comparison of Tc-99m pyrophosphate and Tc-99m methylene diphosphonate in acute myocardial infarction: concise communication. This study compared Tc-99m pyrophosphate (PPi) and Tc-99m methylene diphosphonate (MDP) for myocardial infarct imaging in 24 patients with diagnosed acute myocardial infarction. The radiopharmaceuticals were administered randomly and interpreted without knowledge of the sequence used. Twenty-three patients (96%) had positive Tc-99m PPi scintigrams, but only 17 (71%) had a positive Tc-99m MDP study (P less than 0.05). In addition, a comparison of the relative intensity with each agent revealed greater intensity with Tc-99m in 21 cases, equal intensity in two cases, and less intensity in only one case (p less than 0.001). These findings support the superiority of Tc-99m PPi as the agent of choice for myocardial scintigraphy in acute infarction."}
{"id": "PMID:232148", "title": "Scintigraphic, electrocardiographic, and enzymatic diagnosis of perioperative myocardial infarction in patients undergoing myocardial revascularization.", "content": "To assess the incidence of perioperative myocardial infarction, 214 consecutive patients were evaluated 1-5 days after coronary bypass surgery, using Tc-99m pyrophosphate (TcPPi) myocardial imaging, serial electrocardiograms (ECG), and enzyme levels (SGOT, LDH, CPK). On the basis of the clinical course and scintigraphic, enzymatic, and ECG changes, the diagnosis of perioperative infarction was definite in 17 of 241 cases (7.9%) and probable in six of 241 (2.8%). In all of these 23 patients, TcPPi scans were abnormal; one additional patient had a false-positive scintigram. Only 13 of the 23 had ECG evidence of infarction, but there were no false positives. We set the threshold for abnormality of enzyme changes quite high, owing to experience in more than 900 postoperative patients (SGOT greater than 200, LDH greater than 500, CPK greater than 500 on the same day). Using these criteria, 22 of the 23 infarct patients had abnormal enzymes, and six others were falsely positive. These results indicate a relatively low sensitivity for the ECG in diagnosing perioperative infarction, but the lack of false positives suggests high specificity. The sensitivity and specificity of the enzymes and the TcPPi image were both excellent and quite similar; the main difference was a reduction of certainty of infarction with the enzyme criteria, caused by the six patients whose enzyme values were falsely positive. Considering its sensitivity, specificity, and ability to locate and to a certain extent quantitate necrosis. TcPPi imaging is probably the most valuable means of diagnosing perioperative myocardial infarction.", "contents": "Scintigraphic, electrocardiographic, and enzymatic diagnosis of perioperative myocardial infarction in patients undergoing myocardial revascularization. To assess the incidence of perioperative myocardial infarction, 214 consecutive patients were evaluated 1-5 days after coronary bypass surgery, using Tc-99m pyrophosphate (TcPPi) myocardial imaging, serial electrocardiograms (ECG), and enzyme levels (SGOT, LDH, CPK). On the basis of the clinical course and scintigraphic, enzymatic, and ECG changes, the diagnosis of perioperative infarction was definite in 17 of 241 cases (7.9%) and probable in six of 241 (2.8%). In all of these 23 patients, TcPPi scans were abnormal; one additional patient had a false-positive scintigram. Only 13 of the 23 had ECG evidence of infarction, but there were no false positives. We set the threshold for abnormality of enzyme changes quite high, owing to experience in more than 900 postoperative patients (SGOT greater than 200, LDH greater than 500, CPK greater than 500 on the same day). Using these criteria, 22 of the 23 infarct patients had abnormal enzymes, and six others were falsely positive. These results indicate a relatively low sensitivity for the ECG in diagnosing perioperative infarction, but the lack of false positives suggests high specificity. The sensitivity and specificity of the enzymes and the TcPPi image were both excellent and quite similar; the main difference was a reduction of certainty of infarction with the enzyme criteria, caused by the six patients whose enzyme values were falsely positive. Considering its sensitivity, specificity, and ability to locate and to a certain extent quantitate necrosis. TcPPi imaging is probably the most valuable means of diagnosing perioperative myocardial infarction."}
{"id": "PMID:232149", "title": "Biodistribution and pharmacokinetics of S-35-labeled 5-thio-D-glucose in hamsters bearing pancreatic tumors.", "content": "5-thio-D-glucose (5-TDG) exerts profound effects on rapidly metabolizing tissues. We have used liquid scintillation counting to study the tissue distribution and pharmacokinetics of S-35-labeled 5-TDG in hamster models of pancreatic tumors. In the normal hamster, initial uptake of S-35 activity into kidney, liver, and blood was high, but rapidly decreased with time. The pancreatic uptake (% dose/g) never exceeded 0.75%. This level occurred only at the earliest times after administration. Uptake in all three tumor models exceeded that in pancreatic tissue within 15 min of injection. The highest tumor-to-pancreas ratio was seen in the duct-tumor model, which also exhibited the most favorable tumor-to-tissue ratio when compared with kidney, liver and muscle. Favorable ratios were most pronounced at 6 and 24 hr after injection. These studies provide impetus for the use of 5-TDG as a model compound for the synthesis of potentially useful agents for clinical detection of pancreatic tumors.", "contents": "Biodistribution and pharmacokinetics of S-35-labeled 5-thio-D-glucose in hamsters bearing pancreatic tumors. 5-thio-D-glucose (5-TDG) exerts profound effects on rapidly metabolizing tissues. We have used liquid scintillation counting to study the tissue distribution and pharmacokinetics of S-35-labeled 5-TDG in hamster models of pancreatic tumors. In the normal hamster, initial uptake of S-35 activity into kidney, liver, and blood was high, but rapidly decreased with time. The pancreatic uptake (% dose/g) never exceeded 0.75%. This level occurred only at the earliest times after administration. Uptake in all three tumor models exceeded that in pancreatic tissue within 15 min of injection. The highest tumor-to-pancreas ratio was seen in the duct-tumor model, which also exhibited the most favorable tumor-to-tissue ratio when compared with kidney, liver and muscle. Favorable ratios were most pronounced at 6 and 24 hr after injection. These studies provide impetus for the use of 5-TDG as a model compound for the synthesis of potentially useful agents for clinical detection of pancreatic tumors."}
{"id": "PMID:232155", "title": "A rapid and precise method for the determination of vitamin D3 in rat skin by high-performance liquid chromatography.", "content": "In order to develop the investigations into photobiogenesis of vitamin D3, a rapid and precise method for the determination of the vitamin in rat skin was established by using high-performance liquid chromatography (HPLC). The proposed method included saponification of small pieces of rat skin, extraction of the unsaponifiable matter and application to HPLC using \"Zorbax SIL\" (straight-phase) as an adsorbent and 0.5% isopropanol in n-hexane as a mobile phase. The applicable lower limit of the method was 2ng of vitamin D3/cm2 of subcutaneous tissue-removed skin and it was possible to assay a concentration higher than 2 ng/cm2. The proposed method was applied to determine the content of vitamin D3 in rat skin obtained from in vivo and in vitro irradiation experiments. In the in vitro experiment, the yield of vitamin D3 increased in proportion to the irradiation time. On the other hand, the yield in the in vivo experiment showed a proportional increase similar to the in vitro experiment until 60 min irradiation, while a nearly constant value was obtained by irradiation for longer than 60 min. When the rat skin obtained from the in vitro experiment was irradiated with monochromatic UV rays in the range s60-350 nm, the most effective wavelength for the formation of vitamin D3 was confirmed to be 303 nm, which differs from the result obtained from the experiment in a test tube (295 nm). Moreover, the yield of vitamin D3 by irradiation with UV rays below 288 nm was extremely low, which again differed from the results of a test tube experiment. These differences were thought to be due to the filter effect of the malpighian layer in the epidermis of rat skin.", "contents": "A rapid and precise method for the determination of vitamin D3 in rat skin by high-performance liquid chromatography. In order to develop the investigations into photobiogenesis of vitamin D3, a rapid and precise method for the determination of the vitamin in rat skin was established by using high-performance liquid chromatography (HPLC). The proposed method included saponification of small pieces of rat skin, extraction of the unsaponifiable matter and application to HPLC using \"Zorbax SIL\" (straight-phase) as an adsorbent and 0.5% isopropanol in n-hexane as a mobile phase. The applicable lower limit of the method was 2ng of vitamin D3/cm2 of subcutaneous tissue-removed skin and it was possible to assay a concentration higher than 2 ng/cm2. The proposed method was applied to determine the content of vitamin D3 in rat skin obtained from in vivo and in vitro irradiation experiments. In the in vitro experiment, the yield of vitamin D3 increased in proportion to the irradiation time. On the other hand, the yield in the in vivo experiment showed a proportional increase similar to the in vitro experiment until 60 min irradiation, while a nearly constant value was obtained by irradiation for longer than 60 min. When the rat skin obtained from the in vitro experiment was irradiated with monochromatic UV rays in the range s60-350 nm, the most effective wavelength for the formation of vitamin D3 was confirmed to be 303 nm, which differs from the result obtained from the experiment in a test tube (295 nm). Moreover, the yield of vitamin D3 by irradiation with UV rays below 288 nm was extremely low, which again differed from the results of a test tube experiment. These differences were thought to be due to the filter effect of the malpighian layer in the epidermis of rat skin."}
{"id": "PMID:232157", "title": "Dystrophic calcification in calcifying epithelial odontogenic tumor: an X-ray diffraction and electron spin resonance study.", "content": "X-ray diffraction and electron spin resonance (ESR) analyses were conducted on calcifying epithelial odontogenic tumor (CEOT) associated with abundant calcification in order to compare its mineral structure with that of surrounding cortical bone. The material under investigation was removed from the canine-premolar region of the left maxilla of a 39-year-old woman. The principal findings were that the mineral phase of CEOT consists of apatite crystals and that the crystallinity of the crystals is higher than that of bone apatite. ESR spectra of CEOT are similar to those of bone sample. Quantitative ESR analysis indicates that CEOT shows a higher crystallinity coefficient -- defined by Ostrowski et al. (1972, 1974) as the ratio of spin concentration to the ash content of the sample -- than bone. Based on the data, it can be concluded that the calcification in CEOT has a higher crystalline structure than the cortical bone.", "contents": "Dystrophic calcification in calcifying epithelial odontogenic tumor: an X-ray diffraction and electron spin resonance study. X-ray diffraction and electron spin resonance (ESR) analyses were conducted on calcifying epithelial odontogenic tumor (CEOT) associated with abundant calcification in order to compare its mineral structure with that of surrounding cortical bone. The material under investigation was removed from the canine-premolar region of the left maxilla of a 39-year-old woman. The principal findings were that the mineral phase of CEOT consists of apatite crystals and that the crystallinity of the crystals is higher than that of bone apatite. ESR spectra of CEOT are similar to those of bone sample. Quantitative ESR analysis indicates that CEOT shows a higher crystallinity coefficient -- defined by Ostrowski et al. (1972, 1974) as the ratio of spin concentration to the ash content of the sample -- than bone. Based on the data, it can be concluded that the calcification in CEOT has a higher crystalline structure than the cortical bone."}
{"id": "PMID:232163", "title": "Tryptic peptide analysis of avian oncovirus gag and pol gene products.", "content": "Radiolabeled tryptic peptides of the gag and pol gene products of avian oncoviruses were examined. This analysis included Rous-associated virus 2 structural proteins and the Pr76gag and P180gag-pol proteins in Rous-associated virus 2-infected chicken embryo cells. The methionine- and cysteine-containing tryptic peptides of virion internal structural proteins were present in both Pr76gag and P180gag-pol, suggesting that there was no loss of gag gene-coding sequences during the generation of P180gag-pol. No overlap of gag and pol gene structural information was detected. Analysis of intermediates in the processing of Pr76gag and translation inhibition mapping with pactamycin yielded the following order of structural proteins within the Rous-associated virus 2 Pr76gag precursor: NH2-p19-p12-p27-p15-COOH. The gag and pol sequences missing in the endogenous gsmp120 protein of uninfected gs+ chicken cells were identified by comparison with those of Rous-associated virus 2 P180gag-pol.", "contents": "Tryptic peptide analysis of avian oncovirus gag and pol gene products. Radiolabeled tryptic peptides of the gag and pol gene products of avian oncoviruses were examined. This analysis included Rous-associated virus 2 structural proteins and the Pr76gag and P180gag-pol proteins in Rous-associated virus 2-infected chicken embryo cells. The methionine- and cysteine-containing tryptic peptides of virion internal structural proteins were present in both Pr76gag and P180gag-pol, suggesting that there was no loss of gag gene-coding sequences during the generation of P180gag-pol. No overlap of gag and pol gene structural information was detected. Analysis of intermediates in the processing of Pr76gag and translation inhibition mapping with pactamycin yielded the following order of structural proteins within the Rous-associated virus 2 Pr76gag precursor: NH2-p19-p12-p27-p15-COOH. The gag and pol sequences missing in the endogenous gsmp120 protein of uninfected gs+ chicken cells were identified by comparison with those of Rous-associated virus 2 P180gag-pol."}
{"id": "PMID:232164", "title": "Characterization of the proteins of intracisternal type A and extracellular oncornavirus-like particles produced by MOPC-460 myeloma cells.", "content": "The mouse plasmacytoma cell line, MOPC-460, produces both intracisternal and intracytoplasmic A-type particles when grown as a solid tumor. When these cells are grown either as an ascites tumor or in tissue culture, a third type of particle is produced extracellularly. This particle, the \"myeloma-associated virus,\" is closely related to, and probably an alternate form of, the intracisternal A-type particle. The proteins present in these two types of particles were compared by tryptic peptide mapping. Both types of particles were found to contain essentially the same major proteins of 76,000 (p76), 68,000 to 70,000 (p68-70), and 45,000 (p45) daltons, in addition to varying amounts of smaller proteins. The relative proportions of all these proteins varied from preparation to preparation in an unpredictable way. The p45, p68, and p70 proteins all contained sequences found in p76, suggesting precursor-product relationships of p76 leads to p70 leads to p45 for solid tumor A-type particles and p76 leads to p68 leads to p45 for extracellular myeloma-associated virus. In addition, immune precipitation experiments have established that p76 contains at least some of the antigenic determinants characteristic of murine leukemia virus p30. This confirms earlier nucleic acid hybridization studies which indicated a moderate degree of relatedness between MOPC-460 A-type particles and several standard murine leukemia and sarcoma viruses. Taken together, our results provide evidence supporting the concept that MOPC-460 A-type particles may represent aberrant forms of C-type murine viruses.", "contents": "Characterization of the proteins of intracisternal type A and extracellular oncornavirus-like particles produced by MOPC-460 myeloma cells. The mouse plasmacytoma cell line, MOPC-460, produces both intracisternal and intracytoplasmic A-type particles when grown as a solid tumor. When these cells are grown either as an ascites tumor or in tissue culture, a third type of particle is produced extracellularly. This particle, the \"myeloma-associated virus,\" is closely related to, and probably an alternate form of, the intracisternal A-type particle. The proteins present in these two types of particles were compared by tryptic peptide mapping. Both types of particles were found to contain essentially the same major proteins of 76,000 (p76), 68,000 to 70,000 (p68-70), and 45,000 (p45) daltons, in addition to varying amounts of smaller proteins. The relative proportions of all these proteins varied from preparation to preparation in an unpredictable way. The p45, p68, and p70 proteins all contained sequences found in p76, suggesting precursor-product relationships of p76 leads to p70 leads to p45 for solid tumor A-type particles and p76 leads to p68 leads to p45 for extracellular myeloma-associated virus. In addition, immune precipitation experiments have established that p76 contains at least some of the antigenic determinants characteristic of murine leukemia virus p30. This confirms earlier nucleic acid hybridization studies which indicated a moderate degree of relatedness between MOPC-460 A-type particles and several standard murine leukemia and sarcoma viruses. Taken together, our results provide evidence supporting the concept that MOPC-460 A-type particles may represent aberrant forms of C-type murine viruses."}
{"id": "PMID:232165", "title": "Characterization of infectious oncornaviruses from MOPC-460 plasmacytomas: their relation to A-type particles.", "content": "MOPC-460 mouse plasmacytoma cells produce intracellular A-type particles and extracellular oncornavirus-like particles (\"myeloma-associated virus,\" abbreviated MAV). The genomes of these two particles are closely related. During attempts to establish infections with MOPC-460 extracellular particles, we isolated ecotropic and xenotropic infectious forms of murine leukemia virus. We have investigated the relation of these isolates to A-type particles and to MAV by nucleic acid hybridization. Using complementary DNA probes prepared from the two isolates, we found that these infectious murine leukemia viruses differ from A-type particles and from MAV. Moreover, we found that MAV is the predominant extracellular component: the ecotropic and xenotropic forms of murine leukemia virus were present at only low levels (less than 5%) in MAV preparations. Neither the SC-1 cells infected with ectropic murine leukemia virus nor the mink cells infected with xenotropic murine leukemia virus showed any A-type particles in their cytoplasm when examined by electron microscopy. Our inability to demonstrate infection by the A-type particle-related component, MAV, suggests that these may be defective.", "contents": "Characterization of infectious oncornaviruses from MOPC-460 plasmacytomas: their relation to A-type particles. MOPC-460 mouse plasmacytoma cells produce intracellular A-type particles and extracellular oncornavirus-like particles (\"myeloma-associated virus,\" abbreviated MAV). The genomes of these two particles are closely related. During attempts to establish infections with MOPC-460 extracellular particles, we isolated ecotropic and xenotropic infectious forms of murine leukemia virus. We have investigated the relation of these isolates to A-type particles and to MAV by nucleic acid hybridization. Using complementary DNA probes prepared from the two isolates, we found that these infectious murine leukemia viruses differ from A-type particles and from MAV. Moreover, we found that MAV is the predominant extracellular component: the ecotropic and xenotropic forms of murine leukemia virus were present at only low levels (less than 5%) in MAV preparations. Neither the SC-1 cells infected with ectropic murine leukemia virus nor the mink cells infected with xenotropic murine leukemia virus showed any A-type particles in their cytoplasm when examined by electron microscopy. Our inability to demonstrate infection by the A-type particle-related component, MAV, suggests that these may be defective."}
{"id": "PMID:232166", "title": "Mutant of herpes simplex virus type 2 with temperature-sensitive lesions affecting virion thermostability and DNase activity: identification of the lethal mutation and physical mapping of the nuc-lesion.", "content": "We had previously shown that a temperature-sensitive (ts) mutant of herpes simplex virus type 2 strain HG52, ts13, induced a heat-labile DNase activity in infected cells (B. Francke, H. Moss, M. C. Timbury, and J. Hay, J. Virol. 26:209-213, 1978). Earlier work indicated that the mutant also possessed temperature-sensitive infectivity (I. W. Halliburton and M. C. Timbury, J. Gen. Virol. 30:207-221, 1976). In this study temperature-stable revertants of ts13 have been isolated; examination of them revealed that ts13 is a double mutant, with genetically distinct temperature-sensitive lesions affecting nuclease activity and particle stability. The lethal mutation, in the cell system studied, is the latter. Revertants, which all maintain the nuclease lesion, grew well at a high temperature. Physical mapping of the nuclease lesion placed it between 0.12 and 0.21 (fractional length) on the virus genome, quite distant from the lethal mutation at 0.64 to 0.70.", "contents": "Mutant of herpes simplex virus type 2 with temperature-sensitive lesions affecting virion thermostability and DNase activity: identification of the lethal mutation and physical mapping of the nuc-lesion. We had previously shown that a temperature-sensitive (ts) mutant of herpes simplex virus type 2 strain HG52, ts13, induced a heat-labile DNase activity in infected cells (B. Francke, H. Moss, M. C. Timbury, and J. Hay, J. Virol. 26:209-213, 1978). Earlier work indicated that the mutant also possessed temperature-sensitive infectivity (I. W. Halliburton and M. C. Timbury, J. Gen. Virol. 30:207-221, 1976). In this study temperature-stable revertants of ts13 have been isolated; examination of them revealed that ts13 is a double mutant, with genetically distinct temperature-sensitive lesions affecting nuclease activity and particle stability. The lethal mutation, in the cell system studied, is the latter. Revertants, which all maintain the nuclease lesion, grew well at a high temperature. Physical mapping of the nuclease lesion placed it between 0.12 and 0.21 (fractional length) on the virus genome, quite distant from the lethal mutation at 0.64 to 0.70."}
{"id": "PMID:232167", "title": "Cellular proteins associated with simian virus 40 early gene products in newly infected cells.", "content": "Immunoprecipitates of extracts of simian virus 40-infected permissive monkey kidney cells contained two proteins with molecular weights of 56,000 and 32,000 (52K and 32K) in addition to the known viral early gene products. Immunoprecipitates of cells infected with the 0.54-0.59 deletion mutants that lack the viral 17K gene product did not contain thhe 56K and 32K proteins. The additional proteins appeared in immunoprecipitates of deletion mutant extracts if unlabeled extracts of wild-type-infected cells were added before addition of antiserum. The proteins can also be identified in uninfected cells by co-precipitation with unlabeled viral proteins. Thus, it appears that the 56K and 32K proteins are cellular products that associate with the viral proteins, the 17K in particular, and are indirectly immunoprecipitated by anti-tumor serum.", "contents": "Cellular proteins associated with simian virus 40 early gene products in newly infected cells. Immunoprecipitates of extracts of simian virus 40-infected permissive monkey kidney cells contained two proteins with molecular weights of 56,000 and 32,000 (52K and 32K) in addition to the known viral early gene products. Immunoprecipitates of cells infected with the 0.54-0.59 deletion mutants that lack the viral 17K gene product did not contain thhe 56K and 32K proteins. The additional proteins appeared in immunoprecipitates of deletion mutant extracts if unlabeled extracts of wild-type-infected cells were added before addition of antiserum. The proteins can also be identified in uninfected cells by co-precipitation with unlabeled viral proteins. Thus, it appears that the 56K and 32K proteins are cellular products that associate with the viral proteins, the 17K in particular, and are indirectly immunoprecipitated by anti-tumor serum."}
{"id": "PMID:232168", "title": "Isolation of a soluble and template-dependent poliovirus RNA polymerase that copies virion RNA in vitro.", "content": "A soluble RNA-dependent RNA polymerase was isolated from poliovirus-infected HeLa cells and was shown to copy poliovirus RNA in vitro. The enzyme was purified from a 200,000-X-g supernatant of a cytoplasmic extract of infected cells. The activity of the enzyme was measured throughout the purification by using a polyadenylic acid template and oligouridylic acid primer. The enzyme was partially purified by ammonium sulfate precipitation, glycerol gradient centrifugation, and phosphocellulose chromatography. The polymerase precipitated in a 35% saturated solution of ammonium sulfate, sedimented at about 7S on a glycerol gradient, and eluted from phosphocellulose with 0.15 M KC1. The polymerase was purified about 40-fold and was shown to be totally dependent on exogenous RNA for activity and relatively free of contaminating nuclease. The partially purified polymerase was able to use purified polio virion RNA as well as a template. Under the reaction conditions used, the polymerase required an oligouridylic acid primer and all four ribonucleside triphosphates for activity. The optimum ratio of oligouridylic acid molecules to poliovirus RNA molecules for priming activity was about 16:1. A nearest-neighbor analysis of the in vitro RNA product shows it to be heteropolymeric. Annealing the in vitro product with poliovirus RNA product shows it to be heteropolymeric. Annealing the in vitro product with poliovirus RNA rendered it resistant to RNase digestion, thus suggesting that the product RNA was complementary to the virion RNA template.", "contents": "Isolation of a soluble and template-dependent poliovirus RNA polymerase that copies virion RNA in vitro. A soluble RNA-dependent RNA polymerase was isolated from poliovirus-infected HeLa cells and was shown to copy poliovirus RNA in vitro. The enzyme was purified from a 200,000-X-g supernatant of a cytoplasmic extract of infected cells. The activity of the enzyme was measured throughout the purification by using a polyadenylic acid template and oligouridylic acid primer. The enzyme was partially purified by ammonium sulfate precipitation, glycerol gradient centrifugation, and phosphocellulose chromatography. The polymerase precipitated in a 35% saturated solution of ammonium sulfate, sedimented at about 7S on a glycerol gradient, and eluted from phosphocellulose with 0.15 M KC1. The polymerase was purified about 40-fold and was shown to be totally dependent on exogenous RNA for activity and relatively free of contaminating nuclease. The partially purified polymerase was able to use purified polio virion RNA as well as a template. Under the reaction conditions used, the polymerase required an oligouridylic acid primer and all four ribonucleside triphosphates for activity. The optimum ratio of oligouridylic acid molecules to poliovirus RNA molecules for priming activity was about 16:1. A nearest-neighbor analysis of the in vitro RNA product shows it to be heteropolymeric. Annealing the in vitro product with poliovirus RNA product shows it to be heteropolymeric. Annealing the in vitro product with poliovirus RNA rendered it resistant to RNase digestion, thus suggesting that the product RNA was complementary to the virion RNA template."}
{"id": "PMID:232169", "title": "Terminal sequences of vesicular stomatitis virus RNA are both complementary and conserved.", "content": "The nucleotide sequences at the 5' and 3' termini of RNA isolated from the New Jersey serotype of vesicular stomatitis virus [vsV(NJ)] and two of its defective interfering (DI) particles have been determined. The sequence differs from that previously demonstrated for the RNA from the Indiana serotype of VSV at only 1 of the first 17 positions from the 3' terminus and at only 2 of the first 17 positions from the 5' terminus. The 5'-terminal sequence of VSV(NJ) RNA is the complement of the 3'-terminal sequence, and duplexes which are 20 bases long and contain the 3' and 5' termini have been isolated from this RNA. The RNAs isolated from DI particles of VSV(NJ) have the same base sequences as do the RNAs from the parental virus. These results are in sharp contrast to those obtained with the Indiana serotype of VSV and its DI particles, in which the 3'-terminal sequences differ in 3 positions within the first 17. However, with both serotypes, the 3'-terminal sequence of the DI RNA is the complement of the 5'-terminal sequence of the RNA from the infectious virus. These findings suggest that the 3' and 5' RNA termini are highly conserved in both serotypes and that the 3' terminus of DI RNA is ultimately derived by copying the 5' end of the VSV genome, as recently proposed (D. Kolakofsky, M. Leppert, and L. Kort, in B. W. J. Mahy and R. D. Barry, ed., Negative-Strand Virus and the Host Cell, 1977; M. Leppert, L. Kort, and D. Kolakofsky, Cell 12:539-552, 1977; A. S. Huang, Bacteriol. Rev. 41:811-8218 1977).", "contents": "Terminal sequences of vesicular stomatitis virus RNA are both complementary and conserved. The nucleotide sequences at the 5' and 3' termini of RNA isolated from the New Jersey serotype of vesicular stomatitis virus [vsV(NJ)] and two of its defective interfering (DI) particles have been determined. The sequence differs from that previously demonstrated for the RNA from the Indiana serotype of VSV at only 1 of the first 17 positions from the 3' terminus and at only 2 of the first 17 positions from the 5' terminus. The 5'-terminal sequence of VSV(NJ) RNA is the complement of the 3'-terminal sequence, and duplexes which are 20 bases long and contain the 3' and 5' termini have been isolated from this RNA. The RNAs isolated from DI particles of VSV(NJ) have the same base sequences as do the RNAs from the parental virus. These results are in sharp contrast to those obtained with the Indiana serotype of VSV and its DI particles, in which the 3'-terminal sequences differ in 3 positions within the first 17. However, with both serotypes, the 3'-terminal sequence of the DI RNA is the complement of the 5'-terminal sequence of the RNA from the infectious virus. These findings suggest that the 3' and 5' RNA termini are highly conserved in both serotypes and that the 3' terminus of DI RNA is ultimately derived by copying the 5' end of the VSV genome, as recently proposed (D. Kolakofsky, M. Leppert, and L. Kort, in B. W. J. Mahy and R. D. Barry, ed., Negative-Strand Virus and the Host Cell, 1977; M. Leppert, L. Kort, and D. Kolakofsky, Cell 12:539-552, 1977; A. S. Huang, Bacteriol. Rev. 41:811-8218 1977)."}
{"id": "PMID:232170", "title": "Cell fusion for genetic analysis of two nonconditional Rous sarcoma virus replication mutants.", "content": "Procedures for characterizing replication-defective viruses in nonpermissive mammalian cells were developed and applied to three nonvirogenic Rous sarcoma virus (RSV)-transformed mammalian cell lines--B4, a line of Bryan virus-transformed hamster cells, and two SRD-RSV transformed rat cell lines, LR3/1 and LR3/2. Cell fusion was used to study virus complementation. The three cell lines (i) fused with helper virus-infected chicken cells and the host range of the rescued virus examined, (ii) tested for complementation by fusion with chicken cells exhibiting various patterns of endogenous virus expression, (iii) fused with chicken cells infected with the temperature-sensitive replication mutant LA334 and assayed for complementation at permissive and nonpermissive temperatures, and (iv) tested for complementation of defective viruses in other RSV-transformed mammalian cell lines by fusing pairs of nonvirogenic cell lines and permissive chicken cells. Based upon these complementation studies, we concluded that B4 virus is defective only in the env gene, LR3/) virus is an absolute mutant in the gag and/or pol genes, and LR3/2 virus is a leaky env mutant. Clones of LR3/1 and LR3/2 virus-infected chicken cells were established, and the results obtained from the characterization of these viruses in permissive avian cells substantiates the conclusions reached in the fusion-rescue studies.", "contents": "Cell fusion for genetic analysis of two nonconditional Rous sarcoma virus replication mutants. Procedures for characterizing replication-defective viruses in nonpermissive mammalian cells were developed and applied to three nonvirogenic Rous sarcoma virus (RSV)-transformed mammalian cell lines--B4, a line of Bryan virus-transformed hamster cells, and two SRD-RSV transformed rat cell lines, LR3/1 and LR3/2. Cell fusion was used to study virus complementation. The three cell lines (i) fused with helper virus-infected chicken cells and the host range of the rescued virus examined, (ii) tested for complementation by fusion with chicken cells exhibiting various patterns of endogenous virus expression, (iii) fused with chicken cells infected with the temperature-sensitive replication mutant LA334 and assayed for complementation at permissive and nonpermissive temperatures, and (iv) tested for complementation of defective viruses in other RSV-transformed mammalian cell lines by fusing pairs of nonvirogenic cell lines and permissive chicken cells. Based upon these complementation studies, we concluded that B4 virus is defective only in the env gene, LR3/) virus is an absolute mutant in the gag and/or pol genes, and LR3/2 virus is a leaky env mutant. Clones of LR3/1 and LR3/2 virus-infected chicken cells were established, and the results obtained from the characterization of these viruses in permissive avian cells substantiates the conclusions reached in the fusion-rescue studies."}
{"id": "PMID:232171", "title": "Conserved polynucleotide sequences among the genomes of papillomaviruses.", "content": "The DNAs of different members of the Papillomavirus genus of papovaviruses were analyzed for nucleotide sequence homology. Under standard hybridization conditions (Tm - 28 degrees C), no homology was detectable among the genomes of human papillomavirus type 1 (HPV-1), bovine papillomavirus type 2 (BPV-2), or cottontail rabbit (Shope) papillomavirus (CRPV). However, under less stringent conditions (i.e., Tm - 43 degrees C), stable hybrids were formed between radiolabeled DNAs of CRPV, BPV-1, or BPV-2 and the HindIII-HpaI A, B, and C fragments of HPV-1. Under these same conditions, radiolabeled CRPV and HPV-1 DNAs formed stable hybrids with HincII B and C fragments of BPV-2 DNA. These results indicate that there are regions of homology with as much as 70% base match among all these papillomavirus genomes. Furthermore, unlabeled HPV-1 DNA competitively inhibited the specific hybridization of radiolabeled CRPV DNA to bpv-2 DNA fragments, indicating that the homologous DNA segments are common among these remotely related papillomavirus genomes. These conserved sequences are specific for the Papillomavirus genus of papovaviruses as evidenced by the lack of hybridization between HPV-1 DNA and either simian virus 40 or human papovavirus BK DNA under identical conditions. These results indicate a close evolutionary relationship among the papillomaviruses and further establish the papillomaviruses and polyoma viruses as distinct genera.", "contents": "Conserved polynucleotide sequences among the genomes of papillomaviruses. The DNAs of different members of the Papillomavirus genus of papovaviruses were analyzed for nucleotide sequence homology. Under standard hybridization conditions (Tm - 28 degrees C), no homology was detectable among the genomes of human papillomavirus type 1 (HPV-1), bovine papillomavirus type 2 (BPV-2), or cottontail rabbit (Shope) papillomavirus (CRPV). However, under less stringent conditions (i.e., Tm - 43 degrees C), stable hybrids were formed between radiolabeled DNAs of CRPV, BPV-1, or BPV-2 and the HindIII-HpaI A, B, and C fragments of HPV-1. Under these same conditions, radiolabeled CRPV and HPV-1 DNAs formed stable hybrids with HincII B and C fragments of BPV-2 DNA. These results indicate that there are regions of homology with as much as 70% base match among all these papillomavirus genomes. Furthermore, unlabeled HPV-1 DNA competitively inhibited the specific hybridization of radiolabeled CRPV DNA to bpv-2 DNA fragments, indicating that the homologous DNA segments are common among these remotely related papillomavirus genomes. These conserved sequences are specific for the Papillomavirus genus of papovaviruses as evidenced by the lack of hybridization between HPV-1 DNA and either simian virus 40 or human papovavirus BK DNA under identical conditions. These results indicate a close evolutionary relationship among the papillomaviruses and further establish the papillomaviruses and polyoma viruses as distinct genera."}
{"id": "PMID:232172", "title": "Oligoribonucleotide map and protein of CMII: detection of conserved and nonconserved genetic elements in avian acute leukemia viruses CMII, MC29, and MH2.", "content": "RNA and protein of the defective avian acute leukemia virus CMII, which causes myelocytomas in chickens, and of CMII-associated helper virus (CMIIAV) were investigated. The RNA of CMII measured 6 kilobases (kb) and that of CMIIAV measured 8.5 kb. By comparing more than 20 mapped oligonucleotides of CMII RNA with mapped and nonmapped oligonucleotides of acute leukemia viruses MC29 and MH2 and with mapped oligonucleotides of CMIIAV and other nondefective avian tumor viruses, three segments were distinguished in the oligonucleotide map of CMII RNA: (i) a 5' group-specific segment of 1.5 kb which was conserved among CMII, MC29, and MH2 and also homologous with gag-related oligonucleotides of CMIIAV and other helper viruses (hence, group specific); (ii) an internal segment of 2 kb which was conserved specifically among CMII, MC29, and MH2 and whose presence in CMII lends new support to the view that this class of genetic elements is essential for oncogenicity, because it was absent from an otherwise isogenic, nontransforming helper, CMIIAV; and (iii) a 3' group-specific segment of 2.5 kb which shared 13 of 14 oligonucleotides with CMIIAV and included env oligonucleotides of other nondefective viruses of the avian tumor virus group (hence, group specific). This segment and analogous map segments of MC29 and MH2 were not conserved at the level of shared oligonucleotides. CMII-transformed cells contained a nonstructural, gag gene-related protein of 90,000 daltons, distinguished by its size from 110,000-daltom MC29 and 100,000-dalton MH2 counterparts. The gag relatedness and similarity to the 110,000-dalton MC29 counterpart indicated that the 90,000-dalton CMII protein is translated from the 5' and internal segments of CMII RNA. The existence of conserved 5' and internal RNA segments and conserved nonstructural protein products in CMII, MC29, and MH2 indicates that these viruses belong to a related group, termed here the MC29 group. Viruses of the MC29 group differ from one another mainly in their 3' RNA segments and in minor variations of their conserved RNA segments as well as by strain-specific size markers of their gag-related proteins. Because (i) the conserved 5' gag-related and internal RNA segments and their gag-related, nonvirion protein products correlate with the conserved oncogenic spectra of the MC29 group of viruses and because (ii) the internal RNA sequences and nonvirion proteins are not found in nondefective viruses, we propose that the conserved RNA and protein elements are necessary for oncogenicity and probably are the onc gene products of the MC29 group of viruses.", "contents": "Oligoribonucleotide map and protein of CMII: detection of conserved and nonconserved genetic elements in avian acute leukemia viruses CMII, MC29, and MH2. RNA and protein of the defective avian acute leukemia virus CMII, which causes myelocytomas in chickens, and of CMII-associated helper virus (CMIIAV) were investigated. The RNA of CMII measured 6 kilobases (kb) and that of CMIIAV measured 8.5 kb. By comparing more than 20 mapped oligonucleotides of CMII RNA with mapped and nonmapped oligonucleotides of acute leukemia viruses MC29 and MH2 and with mapped oligonucleotides of CMIIAV and other nondefective avian tumor viruses, three segments were distinguished in the oligonucleotide map of CMII RNA: (i) a 5' group-specific segment of 1.5 kb which was conserved among CMII, MC29, and MH2 and also homologous with gag-related oligonucleotides of CMIIAV and other helper viruses (hence, group specific); (ii) an internal segment of 2 kb which was conserved specifically among CMII, MC29, and MH2 and whose presence in CMII lends new support to the view that this class of genetic elements is essential for oncogenicity, because it was absent from an otherwise isogenic, nontransforming helper, CMIIAV; and (iii) a 3' group-specific segment of 2.5 kb which shared 13 of 14 oligonucleotides with CMIIAV and included env oligonucleotides of other nondefective viruses of the avian tumor virus group (hence, group specific). This segment and analogous map segments of MC29 and MH2 were not conserved at the level of shared oligonucleotides. CMII-transformed cells contained a nonstructural, gag gene-related protein of 90,000 daltons, distinguished by its size from 110,000-daltom MC29 and 100,000-dalton MH2 counterparts. The gag relatedness and similarity to the 110,000-dalton MC29 counterpart indicated that the 90,000-dalton CMII protein is translated from the 5' and internal segments of CMII RNA. The existence of conserved 5' and internal RNA segments and conserved nonstructural protein products in CMII, MC29, and MH2 indicates that these viruses belong to a related group, termed here the MC29 group. Viruses of the MC29 group differ from one another mainly in their 3' RNA segments and in minor variations of their conserved RNA segments as well as by strain-specific size markers of their gag-related proteins. Because (i) the conserved 5' gag-related and internal RNA segments and their gag-related, nonvirion protein products correlate with the conserved oncogenic spectra of the MC29 group of viruses and because (ii) the internal RNA sequences and nonvirion proteins are not found in nondefective viruses, we propose that the conserved RNA and protein elements are necessary for oncogenicity and probably are the onc gene products of the MC29 group of viruses."}
{"id": "PMID:232173", "title": "Comparative analysis of GS and BK virus genomes.", "content": "Analysis of heteroduplexing between the genomes of GS virus, a BK-group virus, and the prototype BK virus revealed one region of nonhomology. Further analysis by cleavage of viral DNA with the restriction endonucleases EcoRI, HindIII, and HaeIII revealed that base changes in the GS virus genome spanned 0.6 to 0.7 map unit from the EcoRI site. Large T and small t antigens of GS virus appear to be similar in size to the BK virus antigens.", "contents": "Comparative analysis of GS and BK virus genomes. Analysis of heteroduplexing between the genomes of GS virus, a BK-group virus, and the prototype BK virus revealed one region of nonhomology. Further analysis by cleavage of viral DNA with the restriction endonucleases EcoRI, HindIII, and HaeIII revealed that base changes in the GS virus genome spanned 0.6 to 0.7 map unit from the EcoRI site. Large T and small t antigens of GS virus appear to be similar in size to the BK virus antigens."}
{"id": "PMID:232174", "title": "Apparent posttranscriptional block to anaerobic induction of endogenous leukemia virus.", "content": "Uninfected Fischer rat cells were induced by anaerobic stress to transcribe high levels of endogenous type C leukemia virus RNA. Complete 35S virus RNA with attached polyadenylic acid sequences was found associated with polysomes, indicating functional mRNA. Since no mature virus was released under these conditions, the presence of a posttranscriptional block to complete virus synthesis is strongly indicated.", "contents": "Apparent posttranscriptional block to anaerobic induction of endogenous leukemia virus. Uninfected Fischer rat cells were induced by anaerobic stress to transcribe high levels of endogenous type C leukemia virus RNA. Complete 35S virus RNA with attached polyadenylic acid sequences was found associated with polysomes, indicating functional mRNA. Since no mature virus was released under these conditions, the presence of a posttranscriptional block to complete virus synthesis is strongly indicated."}
{"id": "PMID:232175", "title": "Structure and function of adenovirus type 12 defective virions.", "content": "Purified human adenovirus type 12 preparations contain defective virions with a lighter density. These defective virions were isolated, and their biological functions and DNA were characterized. They can induce early and late antigens in infected cells and tumors in newborn hamsters with similar efficiency as complete virions. The majority of the DNA molecules from light virions contain deletions mapping near 16% from the left-hand end of the genome. Mechanisms for the generation of these molecules are discussed.", "contents": "Structure and function of adenovirus type 12 defective virions. Purified human adenovirus type 12 preparations contain defective virions with a lighter density. These defective virions were isolated, and their biological functions and DNA were characterized. They can induce early and late antigens in infected cells and tumors in newborn hamsters with similar efficiency as complete virions. The majority of the DNA molecules from light virions contain deletions mapping near 16% from the left-hand end of the genome. Mechanisms for the generation of these molecules are discussed."}
{"id": "PMID:232176", "title": "Impaired maturation of mouse mammary tumor virus precursor polypeptides in lymphoid leukemia cells, producing intracytoplasmic A particles and no extracellular B-type virions.", "content": "Processing of polypeptides of the mouse mammary tumor virus, a type B retrovirus, was investigated in a transplanted thymic lymphoma cell line of the GR strain (GRSL). This cell line was maintained in vivo in ascites form and in vitro as a suspension culture. GRSL cells produce clusters of intracytoplasmic A particles and are virtually deficient in the production of mature extracellular B-type particles. As control, a mammary tumor cell line of the same mouse strain capable of complete virion synthesis was used. The kinetics of viral polypeptide synthesis were studied by pulse labeling with various isotopes (including (35)S and (32)P), followed by immunoprecipitation of cell lysates with monospecific antisera to the major mouse mammary tumor virus gag and env proteins, p27 and gp52, respectively. Both the primary gag and env precursor polypeptides were synthesized in the GRSL cells, but their conversion into viral proteins was impaired. The major gag precursor, Pr73(gag), was stable over a period of 8 h, and mature viral core polypeptides could not be detected. Also, the highly phosphorylated intermediates in the proteolytic processing of Pr73(gag) in virus-producing cells were absent in GRSL cells. By immunoprecipitation, Pr73(gag) was detected in a GRSL particle fraction with the density of intracytoplasmic A particles. The precursor for envelope proteins, Pr73(env), was turned over without the generation of mature viral envelope components gp52 and gp36. The in vivo-transplanted ascites GRSL cells, however, were shown to express gp52 on the cell surface together with a 73,000-dalton polypeptide, as indicated by cell surface iodination and immunoprecipitation.", "contents": "Impaired maturation of mouse mammary tumor virus precursor polypeptides in lymphoid leukemia cells, producing intracytoplasmic A particles and no extracellular B-type virions. Processing of polypeptides of the mouse mammary tumor virus, a type B retrovirus, was investigated in a transplanted thymic lymphoma cell line of the GR strain (GRSL). This cell line was maintained in vivo in ascites form and in vitro as a suspension culture. GRSL cells produce clusters of intracytoplasmic A particles and are virtually deficient in the production of mature extracellular B-type particles. As control, a mammary tumor cell line of the same mouse strain capable of complete virion synthesis was used. The kinetics of viral polypeptide synthesis were studied by pulse labeling with various isotopes (including (35)S and (32)P), followed by immunoprecipitation of cell lysates with monospecific antisera to the major mouse mammary tumor virus gag and env proteins, p27 and gp52, respectively. Both the primary gag and env precursor polypeptides were synthesized in the GRSL cells, but their conversion into viral proteins was impaired. The major gag precursor, Pr73(gag), was stable over a period of 8 h, and mature viral core polypeptides could not be detected. Also, the highly phosphorylated intermediates in the proteolytic processing of Pr73(gag) in virus-producing cells were absent in GRSL cells. By immunoprecipitation, Pr73(gag) was detected in a GRSL particle fraction with the density of intracytoplasmic A particles. The precursor for envelope proteins, Pr73(env), was turned over without the generation of mature viral envelope components gp52 and gp36. The in vivo-transplanted ascites GRSL cells, however, were shown to express gp52 on the cell surface together with a 73,000-dalton polypeptide, as indicated by cell surface iodination and immunoprecipitation."}
{"id": "PMID:232177", "title": "Human cytomegalovirus-induced immediate early antigens: analysis in sodium dodecyl sulfate-polyacrylamide gel electrophoresis after immunoprecipitation.", "content": "Immediate early antigen (IEA) induced in human lung fibroblasts by human cytomegalovirus was characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis after immunoprecipitation with IEA-positive human sera. Two polypeptides of 76,000 daltons (76K) and 82K were detectable within 90 min after infection. Polypeptides of similar molecular weight were also found in immunoprecipitates of human cytomegalovirus-infected cells nonpermissive for virus replication. IEA is located within the nucleus, although some of the 76K material appears to be located on the outer nuclear membrane. Raising salt concentrations in the extraction buffer increased antigen extraction. The contribution of these IEA polypeptides to IEA nuclear fluorescent staining is discussed.", "contents": "Human cytomegalovirus-induced immediate early antigens: analysis in sodium dodecyl sulfate-polyacrylamide gel electrophoresis after immunoprecipitation. Immediate early antigen (IEA) induced in human lung fibroblasts by human cytomegalovirus was characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis after immunoprecipitation with IEA-positive human sera. Two polypeptides of 76,000 daltons (76K) and 82K were detectable within 90 min after infection. Polypeptides of similar molecular weight were also found in immunoprecipitates of human cytomegalovirus-infected cells nonpermissive for virus replication. IEA is located within the nucleus, although some of the 76K material appears to be located on the outer nuclear membrane. Raising salt concentrations in the extraction buffer increased antigen extraction. The contribution of these IEA polypeptides to IEA nuclear fluorescent staining is discussed."}
{"id": "PMID:232178", "title": "Incomplete genomes of the parvovirus minute virus of mice: selective conservation of genome termini, including the origin for DNA replication.", "content": "Deletion mutants of minute virus of mice arising during a single high-multiplicity passage and after serial undiluted passage have been isolated, and the incomplete viral genomes contained therein have been analyzed. The DNA isolated from incomplete virions derived from a single high-multiplicity passage was heterogeneous, ranging in size from 15 to 70% of the intact viral genome, with an average molecular length of approximately, 2,000 nucleotides. Two distinct types of molecules, designated as type I D-DNA and type II D-DNA, could be distinguished on the basis of their degree of secondary structure, and these were present in roughly equal amounts. Type I D-DNAs were predominantly single-stranded, recombinant molecules in which the self-complementary sequences derived from both genomic termini were conserved. The 5' terminus was modified relative to the analogous wild-type structure. Although virtually all of the wild-type genome sequence was seen in the total type I D-DNA population, sequences which map between coordinates 47.3 and 87.1 were clearly underrepresented. However, the extent and position of the deletions in individual molecules varied significantly. The shortest molecules in the population lacked between 90 and 95% of the internal wild-type genome sequence and consisted of sequences derived almost exclusively from within 5.0 map units (250 nucleotides) at both ends of the viral genome. Moreover, these miniature recombinant molecules were selectively amplified during serial undiluted passage and were therefore believed to contain all of the critical recognition sites necessary for the replication of minute virus of mice viral DNA. Type II D-DNAs were virus-specific, double-stranded hairpin molecules whose complementary strands were covalently continuous at variable sites distal to the 5' end of the viral minus strand. In sharp contrast to the type I genomes, these hairpin molecules consisted of sequences which mapped entirely at the 5' end of the viral genome between positions 85.0 and 100. Furthermore, type II molecules were gradually lost from the total D-DNA population during serial undiluted passage, suggesting that these molecules are not competent for DNA Replication but arise as the result of fatal replication errors. Deletion mutants of the type described here for minute virus of mice should be valuable generally as aids to future studies on parvovirus DNA replication, transcription, and cell-virus interactions.", "contents": "Incomplete genomes of the parvovirus minute virus of mice: selective conservation of genome termini, including the origin for DNA replication. Deletion mutants of minute virus of mice arising during a single high-multiplicity passage and after serial undiluted passage have been isolated, and the incomplete viral genomes contained therein have been analyzed. The DNA isolated from incomplete virions derived from a single high-multiplicity passage was heterogeneous, ranging in size from 15 to 70% of the intact viral genome, with an average molecular length of approximately, 2,000 nucleotides. Two distinct types of molecules, designated as type I D-DNA and type II D-DNA, could be distinguished on the basis of their degree of secondary structure, and these were present in roughly equal amounts. Type I D-DNAs were predominantly single-stranded, recombinant molecules in which the self-complementary sequences derived from both genomic termini were conserved. The 5' terminus was modified relative to the analogous wild-type structure. Although virtually all of the wild-type genome sequence was seen in the total type I D-DNA population, sequences which map between coordinates 47.3 and 87.1 were clearly underrepresented. However, the extent and position of the deletions in individual molecules varied significantly. The shortest molecules in the population lacked between 90 and 95% of the internal wild-type genome sequence and consisted of sequences derived almost exclusively from within 5.0 map units (250 nucleotides) at both ends of the viral genome. Moreover, these miniature recombinant molecules were selectively amplified during serial undiluted passage and were therefore believed to contain all of the critical recognition sites necessary for the replication of minute virus of mice viral DNA. Type II D-DNAs were virus-specific, double-stranded hairpin molecules whose complementary strands were covalently continuous at variable sites distal to the 5' end of the viral minus strand. In sharp contrast to the type I genomes, these hairpin molecules consisted of sequences which mapped entirely at the 5' end of the viral genome between positions 85.0 and 100. Furthermore, type II molecules were gradually lost from the total D-DNA population during serial undiluted passage, suggesting that these molecules are not competent for DNA Replication but arise as the result of fatal replication errors. Deletion mutants of the type described here for minute virus of mice should be valuable generally as aids to future studies on parvovirus DNA replication, transcription, and cell-virus interactions."}
{"id": "PMID:232179", "title": "Electron microscopic mapping of RNA transcribed from the late region of polyoma virus DNA.", "content": "The polyoma virus (Py) RNA species transcribed from the L DNA strand of the \"late\" region of the Py genome in Py-infected mouse cells have been mapped by hybridization with specific fragments of Py DNA followed by electron microscopic visualization of the hybrids. Total cellular polyadenylated Py-specific RNA molecules having an S value in the range of 16S to 20S were purified by oligodeoxythymidylic acidcellulose column chromatography, preparative hybridization with Py DNA, and sucrose gradient centrifugation. Cytoplasmic Py-specific RNA was similarily purified, except that it was not fractionated by sucrose gradient centrifugation. Hybrids of these RNA molecules and Py DNA fragments were spread for electron microscopy by either the cytochrome c technique or the bacteriophage T4 gene 32 protein method. The polyadenylic acid at the 3'-end of the RNA in the hybrids was identified by labeling with simian virus 40 DNA circles to which polybromodeoxyuridylic acid tails had been covalently attached. These experiments revealed the presence of three L DNA strand transcripts in both RNA preparations. Two of these RNA molecules were found to be spliced from chains transcribed from two noncontiguous parts of the late region. The third molecule either is a continuous transcript of the entire late region or contains a splicing feature which is too small to be reliably observed by the electron microscope methods used. The 5'-ends of the three RNA species map within a region extending from 68 to 70 map units on the Py restriction endonuclease map. Each of the two spliced molecules contains a 5'-terminal leader sequence transcribed from a DNA segment with an estimated length of 60 to 110 nuvleotides. The 3'-ends of the leaders map at 66.7 +/- 1.0 and 66.4 +/- 0.50 map units. In these molecules the 5'-ends of the other part (the main body) map at 59.4 +/- 0.90 and 49.4 +/- 2.0 map units, respectively. The 3'-termini of all three RNA species map at 24 to 25 map units.", "contents": "Electron microscopic mapping of RNA transcribed from the late region of polyoma virus DNA. The polyoma virus (Py) RNA species transcribed from the L DNA strand of the \"late\" region of the Py genome in Py-infected mouse cells have been mapped by hybridization with specific fragments of Py DNA followed by electron microscopic visualization of the hybrids. Total cellular polyadenylated Py-specific RNA molecules having an S value in the range of 16S to 20S were purified by oligodeoxythymidylic acidcellulose column chromatography, preparative hybridization with Py DNA, and sucrose gradient centrifugation. Cytoplasmic Py-specific RNA was similarily purified, except that it was not fractionated by sucrose gradient centrifugation. Hybrids of these RNA molecules and Py DNA fragments were spread for electron microscopy by either the cytochrome c technique or the bacteriophage T4 gene 32 protein method. The polyadenylic acid at the 3'-end of the RNA in the hybrids was identified by labeling with simian virus 40 DNA circles to which polybromodeoxyuridylic acid tails had been covalently attached. These experiments revealed the presence of three L DNA strand transcripts in both RNA preparations. Two of these RNA molecules were found to be spliced from chains transcribed from two noncontiguous parts of the late region. The third molecule either is a continuous transcript of the entire late region or contains a splicing feature which is too small to be reliably observed by the electron microscope methods used. The 5'-ends of the three RNA species map within a region extending from 68 to 70 map units on the Py restriction endonuclease map. Each of the two spliced molecules contains a 5'-terminal leader sequence transcribed from a DNA segment with an estimated length of 60 to 110 nuvleotides. The 3'-ends of the leaders map at 66.7 +/- 1.0 and 66.4 +/- 0.50 map units. In these molecules the 5'-ends of the other part (the main body) map at 59.4 +/- 0.90 and 49.4 +/- 2.0 map units, respectively. The 3'-termini of all three RNA species map at 24 to 25 map units."}
{"id": "PMID:232180", "title": "Physical map of biologically active Harvey sarcoma virus unintegrated linear DNA.", "content": "BALB/c JLS V9 cells recently infected with Harvey sarcoma virus-murine leukemia virus (HSV-MuLV) complex contained unintegrated HSV linear DNA of 6.0-kilobase pair mass. The cells also contained two HSV closed circular DNA species along with MuLV-encoded linear and closed circular DNA species. HSV 6.0-kilobase pair linear DNA induced focal transformation upon transfection of NIH 3T3 mouse fibroblasts, and the biological activity of HSV DNA did not require helper MuLV functions. A physical map of restriction endonuclease cleavage sites along HSV 6.0-kilobase pair linear DNA was derived. Comparison of this map with one for Moloney MuLV DNA showed that the HSV and Moloney MuLV genomes are identical near their viral RNA 3' ends.", "contents": "Physical map of biologically active Harvey sarcoma virus unintegrated linear DNA. BALB/c JLS V9 cells recently infected with Harvey sarcoma virus-murine leukemia virus (HSV-MuLV) complex contained unintegrated HSV linear DNA of 6.0-kilobase pair mass. The cells also contained two HSV closed circular DNA species along with MuLV-encoded linear and closed circular DNA species. HSV 6.0-kilobase pair linear DNA induced focal transformation upon transfection of NIH 3T3 mouse fibroblasts, and the biological activity of HSV DNA did not require helper MuLV functions. A physical map of restriction endonuclease cleavage sites along HSV 6.0-kilobase pair linear DNA was derived. Comparison of this map with one for Moloney MuLV DNA showed that the HSV and Moloney MuLV genomes are identical near their viral RNA 3' ends."}
{"id": "PMID:232181", "title": "Assembly of vesicular stomatitis virus nucleocapsids in vivo: a kinetic analysis.", "content": "Pulse-chase labeling and cell fractionation were used to examine the pathways taken by the three nucleocapsid polypeptide species of vesicular stomatitis virus into nucleocapsids and then into virions. An improved method of polyacrylamide gel electrophoresis resolved nucleocapsid polypeptides N and NS from cellular actin, facilitating accurate quantitation of the viral polypeptides. Contrary to previous belief, the rate of NS synthesis was found to be a constant fraction of total virus protein synthesis throughout infection, indicating a consistent mechanism of virus protein synthesis regulation. In the kinetic studies, each polypeptide species displayed the following characteristic behavior. (i) Structural polypeptide N was the only species that entered a metabolically active soluble pool before assembly into nucleocapsids. The size of this pool increased with time after infection, causing an increasing delay in the appearance of pulse-labeled N molecules in nucleocapsids. (ii) Throughout infection, the entire complement of L molecules entered nucleocapsids immediately after their synthesis, without diversion through a soluble pool. (iii) Although 75% of newly synthesized molecules of the transcriptase-associated protein NS entered a soluble pool, they never emerged from the compartment. At all times after infection, about 25% of the NS molecules bypassed the soluble pool and entered nucleocapsids directly after their synthesis, as if in concert with L. These results indicate that VSV nucleocapsid assembly in vivo is a stepwise process, comprising an initial condensation of N with the viral RNA, followed by attachment of L and NS, analogous to the stepwise assembly of Sendai virus nucleocapsids. (D. W. Kingsbury, C.-H. Hsu, and K. G. Murti. Virology 91:86-94, 1978). About half of the intracellular nucleocapsids were recovered in a form that sedimented at anomalously low centrifugal forces, reflecting an association with large cellular organelles. This attachment was mediated mainly by electrostatic forces, since these \"bound\" nucleocapsids were released by elevated salt concentrations. The kinetic behavior of nucleocapsid polypeptides was the same in both fractions, providing no evidence for a division of nucleocapsid functions between cellular compartments.", "contents": "Assembly of vesicular stomatitis virus nucleocapsids in vivo: a kinetic analysis. Pulse-chase labeling and cell fractionation were used to examine the pathways taken by the three nucleocapsid polypeptide species of vesicular stomatitis virus into nucleocapsids and then into virions. An improved method of polyacrylamide gel electrophoresis resolved nucleocapsid polypeptides N and NS from cellular actin, facilitating accurate quantitation of the viral polypeptides. Contrary to previous belief, the rate of NS synthesis was found to be a constant fraction of total virus protein synthesis throughout infection, indicating a consistent mechanism of virus protein synthesis regulation. In the kinetic studies, each polypeptide species displayed the following characteristic behavior. (i) Structural polypeptide N was the only species that entered a metabolically active soluble pool before assembly into nucleocapsids. The size of this pool increased with time after infection, causing an increasing delay in the appearance of pulse-labeled N molecules in nucleocapsids. (ii) Throughout infection, the entire complement of L molecules entered nucleocapsids immediately after their synthesis, without diversion through a soluble pool. (iii) Although 75% of newly synthesized molecules of the transcriptase-associated protein NS entered a soluble pool, they never emerged from the compartment. At all times after infection, about 25% of the NS molecules bypassed the soluble pool and entered nucleocapsids directly after their synthesis, as if in concert with L. These results indicate that VSV nucleocapsid assembly in vivo is a stepwise process, comprising an initial condensation of N with the viral RNA, followed by attachment of L and NS, analogous to the stepwise assembly of Sendai virus nucleocapsids. (D. W. Kingsbury, C.-H. Hsu, and K. G. Murti. Virology 91:86-94, 1978). About half of the intracellular nucleocapsids were recovered in a form that sedimented at anomalously low centrifugal forces, reflecting an association with large cellular organelles. This attachment was mediated mainly by electrostatic forces, since these \"bound\" nucleocapsids were released by elevated salt concentrations. The kinetic behavior of nucleocapsid polypeptides was the same in both fractions, providing no evidence for a division of nucleocapsid functions between cellular compartments."}
{"id": "PMID:232182", "title": "Further morphological characterization and structural proteins of infectious bursal disease virus.", "content": "An outer layer surrounding the capsid of infectious bursal disease virus was evident from electron micrographs of intact virus particles having diameters of 62 to 63 nm. The capsid was found to be composed of large morphological units or capsomeres, measuring about 12 nm in diameter. The architecture of the capsid appears to be that of T = 3 symmetry, with a probable 32 morphological units by rotational enhancement of image detail. Structural proteins of infectious bursal disease virus consist of seven species, two major and five minor polypeptides. These are P1 to P7, with molecular weights of 133 x 10(3), 124 x 10(3), 98 x 10(3), 51 x 10(3), 33 x 10(3), 26 x 10(3), and 23 x 10(3), respectively.", "contents": "Further morphological characterization and structural proteins of infectious bursal disease virus. An outer layer surrounding the capsid of infectious bursal disease virus was evident from electron micrographs of intact virus particles having diameters of 62 to 63 nm. The capsid was found to be composed of large morphological units or capsomeres, measuring about 12 nm in diameter. The architecture of the capsid appears to be that of T = 3 symmetry, with a probable 32 morphological units by rotational enhancement of image detail. Structural proteins of infectious bursal disease virus consist of seven species, two major and five minor polypeptides. These are P1 to P7, with molecular weights of 133 x 10(3), 124 x 10(3), 98 x 10(3), 51 x 10(3), 33 x 10(3), 26 x 10(3), and 23 x 10(3), respectively."}
{"id": "PMID:232183", "title": "Secondary structures in polyoma DNA.", "content": "Three reproducible secondary-structure features were observed on single strands of polyoma virus DNA mounted for electron microscopy by the T4 gene 32 protein technique: (i) a hairpin fold-back extending from 92.9 +/- 0.8 to 95.0 +/- 0.7 map units; (ii) a small loop extending from 63.2 +/- 3.1 to 68.5 +/- 2.8 map units; and (iii) a big loop extending from 51.9 +/- 2.3 to 68.9 +/- 2.1 map units. Both loops are bounded by inverted repeat stems of length 40 +/- 20 base pairs. The stem sequences around 68.5 and 68.9 of the large and small loops overlap, either partially or completely. Several lines of evidence indicate that the inverted repeat stems of the two secondary-structure loops lie in the regions of polyoma virus DNA flanking and probably very close to the sequences that are spliced out in the formation of the late 16S and 18S messages, whereas the hairpin fold-back appears to map at a splicing point of an early message. These structures may therefore be important for the processing of the primary transcripts to form the early and late messages.", "contents": "Secondary structures in polyoma DNA. Three reproducible secondary-structure features were observed on single strands of polyoma virus DNA mounted for electron microscopy by the T4 gene 32 protein technique: (i) a hairpin fold-back extending from 92.9 +/- 0.8 to 95.0 +/- 0.7 map units; (ii) a small loop extending from 63.2 +/- 3.1 to 68.5 +/- 2.8 map units; and (iii) a big loop extending from 51.9 +/- 2.3 to 68.9 +/- 2.1 map units. Both loops are bounded by inverted repeat stems of length 40 +/- 20 base pairs. The stem sequences around 68.5 and 68.9 of the large and small loops overlap, either partially or completely. Several lines of evidence indicate that the inverted repeat stems of the two secondary-structure loops lie in the regions of polyoma virus DNA flanking and probably very close to the sequences that are spliced out in the formation of the late 16S and 18S messages, whereas the hairpin fold-back appears to map at a splicing point of an early message. These structures may therefore be important for the processing of the primary transcripts to form the early and late messages."}
{"id": "PMID:232184", "title": "Polymorphism of B-tropic leukemia viruses from BALB/c mice: association of a p30 antigen with N- versus B-tropism.", "content": "Comparison of a number of murine leukemia virus clones by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed extensive protein polymorphism among B-tropic, but not N-tropic, isolates from BALB/c mice, particularly in migration of p30 proteins. A type-specific radioimmunoassay for p30 was developed which uniformly discriminated all B-tropic viruses from N-tropic viruses of BALB/c origin. N- and B-tropic viruses of C57BL/6 and AKR Fv-1b/b origin could also be distinguished by this assay.", "contents": "Polymorphism of B-tropic leukemia viruses from BALB/c mice: association of a p30 antigen with N- versus B-tropism. Comparison of a number of murine leukemia virus clones by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed extensive protein polymorphism among B-tropic, but not N-tropic, isolates from BALB/c mice, particularly in migration of p30 proteins. A type-specific radioimmunoassay for p30 was developed which uniformly discriminated all B-tropic viruses from N-tropic viruses of BALB/c origin. N- and B-tropic viruses of C57BL/6 and AKR Fv-1b/b origin could also be distinguished by this assay."}
{"id": "PMID:232185", "title": "Immune response to the src gene product in mice bearing tumors induced by injection of avian sarcoma virus-transformed mouse cells.", "content": "A single subcutaneous injection of 10(7) live cells of the highly tumorigenic avian sarcoma virus (Schmidt-Ruppin strain, subgroup D)-transformed BALB/c line into BALB/c mice resulted in the production of an antiserum specific for the avian sarcoma virus gene product pp60src. All sera taken from mice 3 weeks after injection of tumor cells contained antibodies to pp60src. Immunoprecipitation experiments showed that all sera precipitated pp60src from Schmidt-Ruppin-infected chicken cells, but only a portion of these sera precipitated pp60src from chicken cells infected with other strains of avian sarcoma virus, i.e., Prague and Bratislava-77. Analysis of the cross-reactivity patterns of these antisera demonstrated a minimum of three to four antigenic determinants on pp60src. The findings reported here should facilitate the production of monoclonal antibodies to pp60src, which in turn will provide highly specific probes for further investigations into the structure and function of this protein.", "contents": "Immune response to the src gene product in mice bearing tumors induced by injection of avian sarcoma virus-transformed mouse cells. A single subcutaneous injection of 10(7) live cells of the highly tumorigenic avian sarcoma virus (Schmidt-Ruppin strain, subgroup D)-transformed BALB/c line into BALB/c mice resulted in the production of an antiserum specific for the avian sarcoma virus gene product pp60src. All sera taken from mice 3 weeks after injection of tumor cells contained antibodies to pp60src. Immunoprecipitation experiments showed that all sera precipitated pp60src from Schmidt-Ruppin-infected chicken cells, but only a portion of these sera precipitated pp60src from chicken cells infected with other strains of avian sarcoma virus, i.e., Prague and Bratislava-77. Analysis of the cross-reactivity patterns of these antisera demonstrated a minimum of three to four antigenic determinants on pp60src. The findings reported here should facilitate the production of monoclonal antibodies to pp60src, which in turn will provide highly specific probes for further investigations into the structure and function of this protein."}
{"id": "PMID:232186", "title": "Expression of simian virus 40 gene A affects tubulin stability.", "content": "The stability of tubulins present in crude extracts of untransformed BALB/c-3T3  mouse fibroblasts, Chinese hamster lung cells, and various of their simian virus 40 transformants was assessed by measurement of their individual colchicine-binding decay rates. In all cases studied the decays followed the kinetics of first-order reactions, and rates were reduced at low temperatures and by vinblastine sulfate. Under all assay conditions, including different temperatures and protein concentrations, tubulins of normal cells decayed considerably faster than those of simian virus 40-transformed cells. Experiments performed with a number of Chinese hamster lung cell clones transformed with temperature-sensitive simian virus 40 gene A mutants showed a clear correlation between increased tubulin stability and the expression of gene A function. These results suggest that it is T-antigen, the viral gene A product, that affects tubulin.", "contents": "Expression of simian virus 40 gene A affects tubulin stability. The stability of tubulins present in crude extracts of untransformed BALB/c-3T3  mouse fibroblasts, Chinese hamster lung cells, and various of their simian virus 40 transformants was assessed by measurement of their individual colchicine-binding decay rates. In all cases studied the decays followed the kinetics of first-order reactions, and rates were reduced at low temperatures and by vinblastine sulfate. Under all assay conditions, including different temperatures and protein concentrations, tubulins of normal cells decayed considerably faster than those of simian virus 40-transformed cells. Experiments performed with a number of Chinese hamster lung cell clones transformed with temperature-sensitive simian virus 40 gene A mutants showed a clear correlation between increased tubulin stability and the expression of gene A function. These results suggest that it is T-antigen, the viral gene A product, that affects tubulin."}
{"id": "PMID:232187", "title": "Methylation of nuclear simian virus 40 RNAs.", "content": "Nuclear RNAs, pulse-labeled with [methyl-3H]methionine and [3H]uridine under optimal conditions, were prepared from cells infected with simian virus 40 at a late time after infection. The labeled RNAs were hybridized with restriction fragments of simian virus 40 DNA. Levels of methyl-3H-labeled RNA annealing with the early (E) or late (L) strands of a particular restriction fragment were compared with [3H]uridine-labeled RNA annealing with the same fragment. The methyl-3H-labeled RNA hybridizing to the various restriction fragments was eluted and analyzed for caps and internal 6-methyladenosine residues. Caps of transcripts of both the L and E strands were primarily located in a fragment containing the origin for viral DNA replication. The highest level of the internal 6-methyladenosine residues in simian virus 40 nuclear RNA was located on the L strand within a fragment from 83 to 0.0 map units and in RNA transcripts from the E strand within a fragment from 37 to 67 map units. Portions of both these regions represent intervening sequences not represented in cyotplasmic mRNA's. Lower levels of internal methylation were found in other locations as well. The potential role of internal 6-methyladenosine residues in RNA processing and transport from the nucleus to the cytoplasm is discussed.", "contents": "Methylation of nuclear simian virus 40 RNAs. Nuclear RNAs, pulse-labeled with [methyl-3H]methionine and [3H]uridine under optimal conditions, were prepared from cells infected with simian virus 40 at a late time after infection. The labeled RNAs were hybridized with restriction fragments of simian virus 40 DNA. Levels of methyl-3H-labeled RNA annealing with the early (E) or late (L) strands of a particular restriction fragment were compared with [3H]uridine-labeled RNA annealing with the same fragment. The methyl-3H-labeled RNA hybridizing to the various restriction fragments was eluted and analyzed for caps and internal 6-methyladenosine residues. Caps of transcripts of both the L and E strands were primarily located in a fragment containing the origin for viral DNA replication. The highest level of the internal 6-methyladenosine residues in simian virus 40 nuclear RNA was located on the L strand within a fragment from 83 to 0.0 map units and in RNA transcripts from the E strand within a fragment from 37 to 67 map units. Portions of both these regions represent intervening sequences not represented in cyotplasmic mRNA's. Lower levels of internal methylation were found in other locations as well. The potential role of internal 6-methyladenosine residues in RNA processing and transport from the nucleus to the cytoplasm is discussed."}
{"id": "PMID:232188", "title": "Adenovirus early function required for protection of viral and cellular DNA.", "content": "Studies were done to characterize a DNA-negative temperature-sensitive (ts) mutant of human adenovirus type 2, H2 ts111. The temperature-sensitive defect, which was reversible on shift-down in the absence of protein synthesis, was expressed as early as 2 h postinfection, and the results of density-labeling experiments are in agreement with at least a DNA replication initiation block. On shift-up, after allowing viral DNA synthesis at permissive temperatures, the newly synthesized viral DNA and the mature viral DNA were cleaved into fragments which sedimented as a broad peak with a mean coefficient of 10-12S. This cleavage was more marked in the presence of hydroxyurea as the DNA synthesis inhibitor. Parental DNA in infected cells was degraded to a much lesser extent regardless of the incubation temperature. In contrast, the parental DNA was strongly degraded when early gene expression was permitted at 33 degrees C before shift-up to 39.5 degrees C. Furthermore, cellular DNA was also degraded at 39.5 degrees C in ts111-infected cells, the rate of cleavage being related to the multiplicity of infection. This cleavage effect, which did not seem to be related to penton base-associated endonuclease activity, was also enhanced when early gene expression was allowed at 33 degrees C before shift-up. The ts111 defect, which was related to an initiation block and endonucleolytic cleavage of viral and cellular DNA, seemed to correspond to a single mutation. The implication of the ts111 gene product in protection of viral and cellular DNA by way of a DNase-inhibitory function is discussed.", "contents": "Adenovirus early function required for protection of viral and cellular DNA. Studies were done to characterize a DNA-negative temperature-sensitive (ts) mutant of human adenovirus type 2, H2 ts111. The temperature-sensitive defect, which was reversible on shift-down in the absence of protein synthesis, was expressed as early as 2 h postinfection, and the results of density-labeling experiments are in agreement with at least a DNA replication initiation block. On shift-up, after allowing viral DNA synthesis at permissive temperatures, the newly synthesized viral DNA and the mature viral DNA were cleaved into fragments which sedimented as a broad peak with a mean coefficient of 10-12S. This cleavage was more marked in the presence of hydroxyurea as the DNA synthesis inhibitor. Parental DNA in infected cells was degraded to a much lesser extent regardless of the incubation temperature. In contrast, the parental DNA was strongly degraded when early gene expression was permitted at 33 degrees C before shift-up to 39.5 degrees C. Furthermore, cellular DNA was also degraded at 39.5 degrees C in ts111-infected cells, the rate of cleavage being related to the multiplicity of infection. This cleavage effect, which did not seem to be related to penton base-associated endonuclease activity, was also enhanced when early gene expression was allowed at 33 degrees C before shift-up. The ts111 defect, which was related to an initiation block and endonucleolytic cleavage of viral and cellular DNA, seemed to correspond to a single mutation. The implication of the ts111 gene product in protection of viral and cellular DNA by way of a DNase-inhibitory function is discussed."}
{"id": "PMID:232189", "title": "Inhibition of herpes simplex virus-induced DNA polymerase activity and viral DNA replication by 9-(2-hydroxyethoxymethyl)guanine and its triphosphate.", "content": "The effect of the nucleoside analog 9-(2-hydroxyethoxymethyl)guanine (acycloguanosine) on herpes simplex virus type 1 DNA synthesis was examined. Acycloguanosine inhibited herpesvirus DNA synthesis in virus-infected cells. The synthesis of host cell DNA was only partially inhibited in actively growing cells at acycloguanosine concentrations several hundred-fold greater than the 50% effective dose for herpes simplex virus type 1. Studies using partially purified enzymes revealed that the triphosphate of this compound inhibited the virus-induced DNA polymerases (DNA nucleotidyltransferases) to a greater degree than the DNA polymerase of the host cell, that the inhibition was dependent upon the base composition of the template, and that the triphosphate was a better substrate for the virus-induced polymerases than for the alpha cellular DNA polymerases.", "contents": "Inhibition of herpes simplex virus-induced DNA polymerase activity and viral DNA replication by 9-(2-hydroxyethoxymethyl)guanine and its triphosphate. The effect of the nucleoside analog 9-(2-hydroxyethoxymethyl)guanine (acycloguanosine) on herpes simplex virus type 1 DNA synthesis was examined. Acycloguanosine inhibited herpesvirus DNA synthesis in virus-infected cells. The synthesis of host cell DNA was only partially inhibited in actively growing cells at acycloguanosine concentrations several hundred-fold greater than the 50% effective dose for herpes simplex virus type 1. Studies using partially purified enzymes revealed that the triphosphate of this compound inhibited the virus-induced DNA polymerases (DNA nucleotidyltransferases) to a greater degree than the DNA polymerase of the host cell, that the inhibition was dependent upon the base composition of the template, and that the triphosphate was a better substrate for the virus-induced polymerases than for the alpha cellular DNA polymerases."}
{"id": "PMID:232190", "title": "Identification of transcribed regions of Epstein-Barr virus DNA in Burkitt lymphoma-derived cells.", "content": "RNA was extracted from the Burkitt lymphoma-derived cell line Raji and from Burkitt lymphoma tumor biopsies, isotope labeled in vitro by iodination with 125I, and hybridized to electrophoretically separated restriction endonuclease fragments of Epstein-Barr virus DNA on nitrocellulose membranes. The results indicated that only certain parts of the Epstein-Barr virus genome are represented as polyribosomal RNA in Raji cells, with a pronounced dominance of RNA sequences complementary to a 2.0 x 10(6)-dalton segment of Epstein-Barr virus DNA located close to the left end of the viral genome. A map of virus-specific polyribosomal RNA sequences was constructed, which indicated that a minimum of three regions of the Epstein-Barr virus genome are expressed in Raji cells. Total-cell RNA preparations from five Burkitt lymphoma biopsies contained RNA sequences homologous to the same regions of Epstein-Barr virus DNA as polyribosomal RNA from Raji cells, albeit at different relative proportions.", "contents": "Identification of transcribed regions of Epstein-Barr virus DNA in Burkitt lymphoma-derived cells. RNA was extracted from the Burkitt lymphoma-derived cell line Raji and from Burkitt lymphoma tumor biopsies, isotope labeled in vitro by iodination with 125I, and hybridized to electrophoretically separated restriction endonuclease fragments of Epstein-Barr virus DNA on nitrocellulose membranes. The results indicated that only certain parts of the Epstein-Barr virus genome are represented as polyribosomal RNA in Raji cells, with a pronounced dominance of RNA sequences complementary to a 2.0 x 10(6)-dalton segment of Epstein-Barr virus DNA located close to the left end of the viral genome. A map of virus-specific polyribosomal RNA sequences was constructed, which indicated that a minimum of three regions of the Epstein-Barr virus genome are expressed in Raji cells. Total-cell RNA preparations from five Burkitt lymphoma biopsies contained RNA sequences homologous to the same regions of Epstein-Barr virus DNA as polyribosomal RNA from Raji cells, albeit at different relative proportions."}
{"id": "PMID:232191", "title": "Adenovirus DNA template for late transcription is not a replicative intermediate.", "content": "The relationship between adenovirus replication and late transcription has been investigated using viral replication and transcription complexes isolated from infected HeLa cell nuclei. These two types of complexes extracted from adenovirus type 2-infected cell nuclei did not sediment at the same rate on sucrose gradients. Viral replicative intermediates were quantitatively precipitated by immunoglobulins raised against purified 72,000-dalton DNA-binding protein, whereas viral transcription complexes remained in the supernatant. These results show that late transcription does not occur on active replication complexes or on 72,000-dalton DNA-binding protein-containing replicative intermediates inactive in DNA synthesis. Additional evidence is presented indicating that it is very unlikely that replicative intermediates lacking the 72,000-dalton DNA-binding protein could be the template for late transcription.", "contents": "Adenovirus DNA template for late transcription is not a replicative intermediate. The relationship between adenovirus replication and late transcription has been investigated using viral replication and transcription complexes isolated from infected HeLa cell nuclei. These two types of complexes extracted from adenovirus type 2-infected cell nuclei did not sediment at the same rate on sucrose gradients. Viral replicative intermediates were quantitatively precipitated by immunoglobulins raised against purified 72,000-dalton DNA-binding protein, whereas viral transcription complexes remained in the supernatant. These results show that late transcription does not occur on active replication complexes or on 72,000-dalton DNA-binding protein-containing replicative intermediates inactive in DNA synthesis. Additional evidence is presented indicating that it is very unlikely that replicative intermediates lacking the 72,000-dalton DNA-binding protein could be the template for late transcription."}
{"id": "PMID:232196", "title": "T lymphocyte-dependent difference in susceptibility between DDD and C3H mice to mouse hepatitis virus, MHV-3.", "content": "After intraperitoneal inculation with a virulent mouse hepatitis virus, MHV-3, 50% lethal dose in DDD mice was about 7 log10 higher than that in C3H mice. Histopathologically, splenic lymphocytes especially of the thymus-dependent area were more severely affected in susceptible C3H mice than in DDD mice. In the liver of C3H mice, virus multiplied exponentially after inoculation, attaining 10(6) PFU at moribund stage, while virus multiplication in DDD mice was much less prominent decreasing remarkably at day 5 or later. The virus could multiply in the primary culture of spleen cells from C3H mice but not in those from DDD mice, and cells supporting virus growth seemed to be a theta-positive population of lymphocytes. No difference was observed between the two strains of mice in the ability of peritoneal macrophages to support virus growth in vitro as well as serum interferon levels after infection.", "contents": "T lymphocyte-dependent difference in susceptibility between DDD and C3H mice to mouse hepatitis virus, MHV-3. After intraperitoneal inculation with a virulent mouse hepatitis virus, MHV-3, 50% lethal dose in DDD mice was about 7 log10 higher than that in C3H mice. Histopathologically, splenic lymphocytes especially of the thymus-dependent area were more severely affected in susceptible C3H mice than in DDD mice. In the liver of C3H mice, virus multiplied exponentially after inoculation, attaining 10(6) PFU at moribund stage, while virus multiplication in DDD mice was much less prominent decreasing remarkably at day 5 or later. The virus could multiply in the primary culture of spleen cells from C3H mice but not in those from DDD mice, and cells supporting virus growth seemed to be a theta-positive population of lymphocytes. No difference was observed between the two strains of mice in the ability of peritoneal macrophages to support virus growth in vitro as well as serum interferon levels after infection."}
{"id": "PMID:232199", "title": "Correlation of cyclic AMP and cyclic GMP levels with changes in contractile force of dog ventricular myocardium during cholinergic antagonism of positive inotropic actions of histamine, glucagon, theophylline and papaverine.", "content": "On the dog isolated right ventricular muscle, experiments were carried out in order to elucidate the characteristics of the cholinergic antagonism against the positive inotropic action (PIA) induced via different subcellular mechanisms. The relationship between cyclic AMP and cyclic GMP levels, and contractile force during cholinergic antagonism was assessed. Carbachol (10 microM) by itself decreased only slightly the tension developed, but inhibited prominently the PIAs of isoprenaline, histamine, glucagon, theophylline and papaverine. The action of dibutyryl cyclic AMP was inhibited less than PIAs of other agents mentioned above. In contrast, carbachol did not affect the PIAs of calcium and g-strophanthin. The antagonism by carbachol of PIAs of isoprenaline, histamine, glucagon, theophylline and papaverine was accompanied by a reduction of the intracellular cyclic AMP level elevated previously by these agents, and by an elevation of the intracellular cyclic GMP level. A good correlation was found between changes in the tension developed, and cyclic AMP and cyclic GMP levels during the cholinergic antagonism of PIAs induced by these agents in the dog ventricular myocardium.", "contents": "Correlation of cyclic AMP and cyclic GMP levels with changes in contractile force of dog ventricular myocardium during cholinergic antagonism of positive inotropic actions of histamine, glucagon, theophylline and papaverine. On the dog isolated right ventricular muscle, experiments were carried out in order to elucidate the characteristics of the cholinergic antagonism against the positive inotropic action (PIA) induced via different subcellular mechanisms. The relationship between cyclic AMP and cyclic GMP levels, and contractile force during cholinergic antagonism was assessed. Carbachol (10 microM) by itself decreased only slightly the tension developed, but inhibited prominently the PIAs of isoprenaline, histamine, glucagon, theophylline and papaverine. The action of dibutyryl cyclic AMP was inhibited less than PIAs of other agents mentioned above. In contrast, carbachol did not affect the PIAs of calcium and g-strophanthin. The antagonism by carbachol of PIAs of isoprenaline, histamine, glucagon, theophylline and papaverine was accompanied by a reduction of the intracellular cyclic AMP level elevated previously by these agents, and by an elevation of the intracellular cyclic GMP level. A good correlation was found between changes in the tension developed, and cyclic AMP and cyclic GMP levels during the cholinergic antagonism of PIAs induced by these agents in the dog ventricular myocardium."}
{"id": "PMID:232200", "title": "Effects of phenylephrine and isoproterenol on the activity of cyclic AMP-dependent protein kinase of hypothyroid rat tissues.", "content": "The present study was designed to examine the properties of cyclic AMP-dependent protein kinase from normal and hypothyroid rat tissues. The activity of the liver enzyme decreased in hypothyroid rats and this reduced activity may be due to the decrease in synthesis of enzyme protein. The enzyme activity from the kidney of hypothyroid rats increased by 35% in the absence of cyclic AMP. Further, the enzyme from the kidney of hypothyroid animals responded to phenylephrine and isoproterenol. In the heart, the basal enzyme activity was the same in both groups, but the enzyme from the heart of hypothyroid animals did not respond to isoproterenol. When hypothyroid rats were treated with 3,3',5-triiodothyronine, the enzyme activities from those rat tissues showed essentially the same level as those of the corresponding normal ones. These results suggest that thyroid hormone regulates adrenergic agonists-mediated responses both at the sites of adrenoceptors and that of protein phosphorylation. Furthermore, the dependence on thyroid hormone varies according to the tissue.", "contents": "Effects of phenylephrine and isoproterenol on the activity of cyclic AMP-dependent protein kinase of hypothyroid rat tissues. The present study was designed to examine the properties of cyclic AMP-dependent protein kinase from normal and hypothyroid rat tissues. The activity of the liver enzyme decreased in hypothyroid rats and this reduced activity may be due to the decrease in synthesis of enzyme protein. The enzyme activity from the kidney of hypothyroid rats increased by 35% in the absence of cyclic AMP. Further, the enzyme from the kidney of hypothyroid animals responded to phenylephrine and isoproterenol. In the heart, the basal enzyme activity was the same in both groups, but the enzyme from the heart of hypothyroid animals did not respond to isoproterenol. When hypothyroid rats were treated with 3,3',5-triiodothyronine, the enzyme activities from those rat tissues showed essentially the same level as those of the corresponding normal ones. These results suggest that thyroid hormone regulates adrenergic agonists-mediated responses both at the sites of adrenoceptors and that of protein phosphorylation. Furthermore, the dependence on thyroid hormone varies according to the tissue."}
{"id": "PMID:232202", "title": "[Influence of hyperthermia on toxic side effects of cytostatic agents (author's transl)].", "content": "14 patients with tumors in generalised stages (Hodgkin's disease, oat-cell-carcinoma, Fibrosarcoma, acute leukemia) were treated altogether 54 times with cytostatics in combination with hyperthermia. The temperature was induced by microwaves with a frequency of 27 MHz. A temperature of 40 degrees C was reached after 40 min. At this point cytostatics were applicated; afterwards the temperature was maintained for one hour at 40-40,5 degrees C. Cardia, pulmonary and circulatory complications did not occur. Controls of the laboratory parameters could exclude effects on electrolytes, muscles, blood, liver and kidney. The laboratory controls were made before, during, immediately after and 24 h after hyperthermia. There were no signs for an enhancement of toxicity typical for cytostatics. The observations are compared to the results of other investigators. To date the therapeutic effect of this treatment can not be stated.", "contents": "[Influence of hyperthermia on toxic side effects of cytostatic agents (author's transl)]. 14 patients with tumors in generalised stages (Hodgkin's disease, oat-cell-carcinoma, Fibrosarcoma, acute leukemia) were treated altogether 54 times with cytostatics in combination with hyperthermia. The temperature was induced by microwaves with a frequency of 27 MHz. A temperature of 40 degrees C was reached after 40 min. At this point cytostatics were applicated; afterwards the temperature was maintained for one hour at 40-40,5 degrees C. Cardia, pulmonary and circulatory complications did not occur. Controls of the laboratory parameters could exclude effects on electrolytes, muscles, blood, liver and kidney. The laboratory controls were made before, during, immediately after and 24 h after hyperthermia. There were no signs for an enhancement of toxicity typical for cytostatics. The observations are compared to the results of other investigators. To date the therapeutic effect of this treatment can not be stated."}
{"id": "PMID:232204", "title": "Plants used as abortifacients and emmenagogues by Spanish New Mexicans.", "content": "Individuals of Spanish and Mexican descent in New Mexico have used a number of plants as emmenagogues and abortifacients. Of the plants used, cotton root bark (Gossypium sp.), inmortal ((Asclepias capricornu Woodson), poleo chino (Hedeoma oblongifolia (Gray) Heller), rue Ruta graveolens L.), wormseed (Chenopodium ambrosioides L.), and three species of Artemesia seem to be used most widely. Of these, the cotton root bark, when used as an abortifacient, seems to exhibit the lowest toxicity. Rue is notable because of its use independently within different cultures, but may exhibit toxic side effects when used as an abortifacient. Seven other plants are outlined on the basis of anecdotal and folkloric reports. Investigations are underway to look at use effectiveness, side effects, impact on fertility, and acceptance among cultures of the Southwestern United States.", "contents": "Plants used as abortifacients and emmenagogues by Spanish New Mexicans. Individuals of Spanish and Mexican descent in New Mexico have used a number of plants as emmenagogues and abortifacients. Of the plants used, cotton root bark (Gossypium sp.), inmortal ((Asclepias capricornu Woodson), poleo chino (Hedeoma oblongifolia (Gray) Heller), rue Ruta graveolens L.), wormseed (Chenopodium ambrosioides L.), and three species of Artemesia seem to be used most widely. Of these, the cotton root bark, when used as an abortifacient, seems to exhibit the lowest toxicity. Rue is notable because of its use independently within different cultures, but may exhibit toxic side effects when used as an abortifacient. Seven other plants are outlined on the basis of anecdotal and folkloric reports. Investigations are underway to look at use effectiveness, side effects, impact on fertility, and acceptance among cultures of the Southwestern United States."}
{"id": "PMID:232228", "title": "Transposon 10 promoted deletions and inversions in the transfer genes of R100-1.", "content": "Spontaneous tetracycline-sensitive, transfer-deficient mutants of R100-1 were selected and analysed by genetic complementation tests and with the restriction endonuclease EcoR1. While some of the Tets Tra- mutants were caused by a single deletion event which removed the Tetr genes and extended into the neighbouring transfer genes, other mutants were the result of the deletion of the Tetr genes within Tn10 which was accompanied by an inversion of adjacent DNA sequences. A clustering of deletion and inversion endpoints occurred in the traA gene. Some of the transfer genes of R100-1 were assigned to EcoR1 fragments.", "contents": "Transposon 10 promoted deletions and inversions in the transfer genes of R100-1. Spontaneous tetracycline-sensitive, transfer-deficient mutants of R100-1 were selected and analysed by genetic complementation tests and with the restriction endonuclease EcoR1. While some of the Tets Tra- mutants were caused by a single deletion event which removed the Tetr genes and extended into the neighbouring transfer genes, other mutants were the result of the deletion of the Tetr genes within Tn10 which was accompanied by an inversion of adjacent DNA sequences. A clustering of deletion and inversion endpoints occurred in the traA gene. Some of the transfer genes of R100-1 were assigned to EcoR1 fragments."}
{"id": "PMID:232229", "title": "A kinetic analysis of cell division, and induction and stability of recA protein in U.V. Irradiated ion+ and ion-strains of Escherichia coli K12.", "content": "Kinetic analysis of induction of recA protein synthesis after U.V. irradiation does not show correspondence with the kinetics of division inhibition in ion+ and ion- strains. When the induction of recA protein after U.V. is drastically reduced by rifampicin treatment, no effect on the kinetics of division inhibition is observed.", "contents": "A kinetic analysis of cell division, and induction and stability of recA protein in U.V. Irradiated ion+ and ion-strains of Escherichia coli K12. Kinetic analysis of induction of recA protein synthesis after U.V. irradiation does not show correspondence with the kinetics of division inhibition in ion+ and ion- strains. When the induction of recA protein after U.V. is drastically reduced by rifampicin treatment, no effect on the kinetics of division inhibition is observed."}
{"id": "PMID:232230", "title": "Chromosomal mobilization from a recA mutant of Pseudomonas putida.", "content": "A methyl methane sulfonate sensitive mutant of P. putida strain PpG1 is also extremely sensitive to UV-rays, compared to parent wild type cells. This mutant behaves typically as recombination less (recA) mutants of Escherichia coli and Pseudomonas aeruginosa, since as a recipient, it exhibits extremely low frequency of recombination following conjugational, transductional, and transformational gene transfer. Sex factor plasmids such as K-XYL or TOL can mobilize chromosomal genes equally well both from recA+ and recA801 donor cells, suggesting that host recombination functions are not necessary for mobilization of chromosomal genes by such plasmids.", "contents": "Chromosomal mobilization from a recA mutant of Pseudomonas putida. A methyl methane sulfonate sensitive mutant of P. putida strain PpG1 is also extremely sensitive to UV-rays, compared to parent wild type cells. This mutant behaves typically as recombination less (recA) mutants of Escherichia coli and Pseudomonas aeruginosa, since as a recipient, it exhibits extremely low frequency of recombination following conjugational, transductional, and transformational gene transfer. Sex factor plasmids such as K-XYL or TOL can mobilize chromosomal genes equally well both from recA+ and recA801 donor cells, suggesting that host recombination functions are not necessary for mobilization of chromosomal genes by such plasmids."}
{"id": "PMID:232232", "title": "Altered linkage values in phage P22--mediated transduction caused by distant deletions or insertions in donor chromosomes.", "content": "The effects of distant deletions or insertions in the Salmonella typhimurium donor strains on P22--mediated cotransducibility of genetic markers was studied. We found that deletions of histidine operon, unit 44 of the chromosome map, changed the linkage of markers purF and aroC (unit 49) and pyrF and trpA (unit 34). They did not change the linkage of more distant markers pyrE and cysE. The effect of three types of insertions was examined. The donor strains carried F factor, Tn10 transposon or pi-his duplication inserted close to histidine operon. These insertions caused alteration of purF-aroC linkage while pyrF-trpA cotransduction values were not affected. These data show that the effect of the chromosome rearrangements extends to at least 5% of S. typhimurium chromosome length and may reach as much as 10% of it. Our results are in agreement with the model of Chelala and Margolin (1974) concerning formation of transduction particles. They indicate that the cotransducibility changes caused by deletions or insertions extent further than it might have been expected from previous reports.", "contents": "Altered linkage values in phage P22--mediated transduction caused by distant deletions or insertions in donor chromosomes. The effects of distant deletions or insertions in the Salmonella typhimurium donor strains on P22--mediated cotransducibility of genetic markers was studied. We found that deletions of histidine operon, unit 44 of the chromosome map, changed the linkage of markers purF and aroC (unit 49) and pyrF and trpA (unit 34). They did not change the linkage of more distant markers pyrE and cysE. The effect of three types of insertions was examined. The donor strains carried F factor, Tn10 transposon or pi-his duplication inserted close to histidine operon. These insertions caused alteration of purF-aroC linkage while pyrF-trpA cotransduction values were not affected. These data show that the effect of the chromosome rearrangements extends to at least 5% of S. typhimurium chromosome length and may reach as much as 10% of it. Our results are in agreement with the model of Chelala and Margolin (1974) concerning formation of transduction particles. They indicate that the cotransducibility changes caused by deletions or insertions extent further than it might have been expected from previous reports."}
{"id": "PMID:232233", "title": "Sensitivity of chemically treated spores of Clostridium perfringens type A to an initiation protein.", "content": "Extraction of Clostridium perfringens type A spores with dithiothreitol (DTT), DTT plus sodium dodecyl sulphate (DTT-SDS), urea-mercaptoethanol (UME), or alkali, solubilized from 18.6 to 46.5 of the total dry weight of spores. The initiation of germination and lysis of such treated spores with lysozyme and an initiation protein (IP) from the culture supernatant fluid of sporulating cells of C. perfringens was studied under various conditions. The ability of lysozyme and the crude IP to induce germination and lysis of extracted spores was concentration dependent up to 0.5 microgram/ml and 5.6 mg/ml respectively. IP showed an optimum of activity between pH 7 and 8 for DTT-SDS and DTT extracted spores, and between pH 6 and 9 for UME extracted spores. The optimum temperature of activity for IP was 55 degrees C. Dissimilarities in the extent to which lysozyme and the IP initiated germination and lysis of spores extracted by various methods may have been a reflection of the differences in amounts of protein solubilized by each treatment.", "contents": "Sensitivity of chemically treated spores of Clostridium perfringens type A to an initiation protein. Extraction of Clostridium perfringens type A spores with dithiothreitol (DTT), DTT plus sodium dodecyl sulphate (DTT-SDS), urea-mercaptoethanol (UME), or alkali, solubilized from 18.6 to 46.5 of the total dry weight of spores. The initiation of germination and lysis of such treated spores with lysozyme and an initiation protein (IP) from the culture supernatant fluid of sporulating cells of C. perfringens was studied under various conditions. The ability of lysozyme and the crude IP to induce germination and lysis of extracted spores was concentration dependent up to 0.5 microgram/ml and 5.6 mg/ml respectively. IP showed an optimum of activity between pH 7 and 8 for DTT-SDS and DTT extracted spores, and between pH 6 and 9 for UME extracted spores. The optimum temperature of activity for IP was 55 degrees C. Dissimilarities in the extent to which lysozyme and the IP initiated germination and lysis of spores extracted by various methods may have been a reflection of the differences in amounts of protein solubilized by each treatment."}
{"id": "PMID:232234", "title": "Measurement of pyrimidine dimers in spheroplasts of Bacillus subtilis.", "content": "A method is described for making spheroplasts of Bacillus subtilis which are permeable to exogenous enzymes. Conditions are described for measuring small numbers of pyrimidine dimers in the DNA of UV-irradiated cells by use of a partially purified Micrococcus luteus extract containing an enzyme specific for pyrimidine dimers. The system will detect as few as 10-12 pyrimidine dimers per genome.", "contents": "Measurement of pyrimidine dimers in spheroplasts of Bacillus subtilis. A method is described for making spheroplasts of Bacillus subtilis which are permeable to exogenous enzymes. Conditions are described for measuring small numbers of pyrimidine dimers in the DNA of UV-irradiated cells by use of a partially purified Micrococcus luteus extract containing an enzyme specific for pyrimidine dimers. The system will detect as few as 10-12 pyrimidine dimers per genome."}
{"id": "PMID:232235", "title": "The physical state of herpes simplex virus DNA in infected human cells.", "content": "Treatment of herpes simplex virus type 1 (HSV-1)-infected human embryo lung (HEL) cells with phosphonoacetic acid (PAA) resulted in complete inhibition of HSV DNA replication. DNA was extracted from PAA-treated HEL cells infected with HSV-1 and centrifuged in a neutral CsCl density gradient. The HSV DNA sequences in the nuclei of PAA treated cells at 24 hr post infection banded at the same density as free HSV DNA (1.725 g/cm3), but a significant amount of viral DNA sequences were detected in the regions of cell DNA (1.700 g/cm3) as well as in the intermediate fractions as determined by hybridization with 3H HSV complementary RNA. The viral DNA sequences of lower deisntiy did not change in density by recentrifugation in a CsCl density gradient, but did change to the density of free viral DNA after treatment with EcoR1 restriction endonuclease. When the DNA from the nuclei of PAA treated cells was analyzed in an alkaline glycerol gradient, more than 95% of the viral DNA sequences were found in the free viral DNA fractions. Since the viral and cellular hybrid DNA represented approximately 33% of the total viral DNA sequences, it is concluded that some of the HSV DNA sequences in PAA treated, infected cells are associated with cell DNA by alkali-labile bonds.", "contents": "The physical state of herpes simplex virus DNA in infected human cells. Treatment of herpes simplex virus type 1 (HSV-1)-infected human embryo lung (HEL) cells with phosphonoacetic acid (PAA) resulted in complete inhibition of HSV DNA replication. DNA was extracted from PAA-treated HEL cells infected with HSV-1 and centrifuged in a neutral CsCl density gradient. The HSV DNA sequences in the nuclei of PAA treated cells at 24 hr post infection banded at the same density as free HSV DNA (1.725 g/cm3), but a significant amount of viral DNA sequences were detected in the regions of cell DNA (1.700 g/cm3) as well as in the intermediate fractions as determined by hybridization with 3H HSV complementary RNA. The viral DNA sequences of lower deisntiy did not change in density by recentrifugation in a CsCl density gradient, but did change to the density of free viral DNA after treatment with EcoR1 restriction endonuclease. When the DNA from the nuclei of PAA treated cells was analyzed in an alkaline glycerol gradient, more than 95% of the viral DNA sequences were found in the free viral DNA fractions. Since the viral and cellular hybrid DNA represented approximately 33% of the total viral DNA sequences, it is concluded that some of the HSV DNA sequences in PAA treated, infected cells are associated with cell DNA by alkali-labile bonds."}
{"id": "PMID:232236", "title": "Heterogeneous RNA of the Prague strain of Rous sarcoma virus caused by undiluted passages.", "content": "The size of genomic RNA in PR-RSV A passaged in chick embryo fibroblasts (CEF) or quail embryo fibroblasts (QEF) was determined by gel electrophoresis. The results showed that 3 undiluted passages resulted in heterogeneity of RNA. The heterogeneity of the smaller incomplete RNAs in the virus stock was decreased by diluted passage or cloning, but RNA of the b subunit size and a subunit RNA of complete genome size were relatively stable. These heterogeneous RNAs were characterized by hybridization analysis. The RNAs from 4 peaks hybridized with both cDNAtotal and cDNAsrc to appreciable extents, indicating that they were derived from viral RNA and that at least some of them contained the src sequence. This finding and the failure to isolate a td mutant from the undiluted-passaged virus stock or from some subclones that had a and b subunits of RNA indicate that the td virus was only a minor constituent of the incomplete virus population caused by undiluted passages. Some viruses with incomplete RNA in the virus stock could produce foci with the aid of td B77 or RAV-60. The emergence of rd viruses by undiluted passages was indicated.", "contents": "Heterogeneous RNA of the Prague strain of Rous sarcoma virus caused by undiluted passages. The size of genomic RNA in PR-RSV A passaged in chick embryo fibroblasts (CEF) or quail embryo fibroblasts (QEF) was determined by gel electrophoresis. The results showed that 3 undiluted passages resulted in heterogeneity of RNA. The heterogeneity of the smaller incomplete RNAs in the virus stock was decreased by diluted passage or cloning, but RNA of the b subunit size and a subunit RNA of complete genome size were relatively stable. These heterogeneous RNAs were characterized by hybridization analysis. The RNAs from 4 peaks hybridized with both cDNAtotal and cDNAsrc to appreciable extents, indicating that they were derived from viral RNA and that at least some of them contained the src sequence. This finding and the failure to isolate a td mutant from the undiluted-passaged virus stock or from some subclones that had a and b subunits of RNA indicate that the td virus was only a minor constituent of the incomplete virus population caused by undiluted passages. Some viruses with incomplete RNA in the virus stock could produce foci with the aid of td B77 or RAV-60. The emergence of rd viruses by undiluted passages was indicated."}
{"id": "PMID:232239", "title": "Combination radiotherapy and chemotherapy for small cell carcinoma of the lung.", "content": "Twenty previously untreated patients with small cell carcinoma of the lung were treated with cyclophosphamide, 400 mg/m2 and Adriamycin, 40 mg/m2 IV on day 1, followed by cytosine arabinoside, 20 mg/m2, every 12 hours subcutaneously on days 5--9; this regimen was repeated every 28 days. On days 14--28 of the first cycle, each patient received 3,000 rads to the primary tumor and whole brain. Following eleven courses, Adriamycin was discontinued and patients received cyclophosphamide, 800 mg/m2 IV on day 1 and methotrexate, 15 mg/m2 IV on days 5--7. This regimen was repeated every 28 days. Toxicity included nausea, vomiting, alopecia, leukopenia, thrombocytopenia, and esophagitis. Overall response rate was 65%. Media survival in limited disease was 14.5 months, and in extended disease it was 4.5 months. This combination is active in localized small cell carcinoma but provides no superiority over other regimens.", "contents": "Combination radiotherapy and chemotherapy for small cell carcinoma of the lung. Twenty previously untreated patients with small cell carcinoma of the lung were treated with cyclophosphamide, 400 mg/m2 and Adriamycin, 40 mg/m2 IV on day 1, followed by cytosine arabinoside, 20 mg/m2, every 12 hours subcutaneously on days 5--9; this regimen was repeated every 28 days. On days 14--28 of the first cycle, each patient received 3,000 rads to the primary tumor and whole brain. Following eleven courses, Adriamycin was discontinued and patients received cyclophosphamide, 800 mg/m2 IV on day 1 and methotrexate, 15 mg/m2 IV on days 5--7. This regimen was repeated every 28 days. Toxicity included nausea, vomiting, alopecia, leukopenia, thrombocytopenia, and esophagitis. Overall response rate was 65%. Media survival in limited disease was 14.5 months, and in extended disease it was 4.5 months. This combination is active in localized small cell carcinoma but provides no superiority over other regimens."}
{"id": "PMID:232240", "title": "Inflammatory fibrous histiocytoma: response to non-surgical therapy: a case report.", "content": "A case of inflammatory fibrous histiocytoma arising in soft tissue near the sacrum is presented. The patient's mode of presentation, clinical course, and tumor histology were typical of this disease. The tumor was inoperable, and radiotherapy combined with doxorubicin, cyclophosphamide, and intermediate-dose oral methotrexate produced a dramatic complete response lasting over 27 months. Favorable results with nonsurgical therapy have not previously been reported for this disease. The gratifying result obtained, although of relatively short duration to date, indicates that combined modality therapy may provide significant back-up to aggressive surgery. The use of these agents in an adjuvant setting merits study.", "contents": "Inflammatory fibrous histiocytoma: response to non-surgical therapy: a case report. A case of inflammatory fibrous histiocytoma arising in soft tissue near the sacrum is presented. The patient's mode of presentation, clinical course, and tumor histology were typical of this disease. The tumor was inoperable, and radiotherapy combined with doxorubicin, cyclophosphamide, and intermediate-dose oral methotrexate produced a dramatic complete response lasting over 27 months. Favorable results with nonsurgical therapy have not previously been reported for this disease. The gratifying result obtained, although of relatively short duration to date, indicates that combined modality therapy may provide significant back-up to aggressive surgery. The use of these agents in an adjuvant setting merits study."}
{"id": "PMID:232247", "title": "[Worldwide eradication of smallpox or from Sarah Nelmes to Ali Maow Maalin].", "content": "It cannot be disputed that the WHO plan for the eradication of smallpox has had considerable success. There is no endemic smallpox any longer in the world. Nevertheless caution is advised and continued supervision must not be neglected. There are still countries where supervision is not satisfactory, there is uncertainty about animal reservoirs and it should be assumed from the beginning that up to the present no epidemic disease could be completely eradicated. For this reason it is inevitable that supplies of vaccine should be available. A vaccine from heat sensitive strains is offered which is obtained from cell cultures.", "contents": "[Worldwide eradication of smallpox or from Sarah Nelmes to Ali Maow Maalin]. It cannot be disputed that the WHO plan for the eradication of smallpox has had considerable success. There is no endemic smallpox any longer in the world. Nevertheless caution is advised and continued supervision must not be neglected. There are still countries where supervision is not satisfactory, there is uncertainty about animal reservoirs and it should be assumed from the beginning that up to the present no epidemic disease could be completely eradicated. For this reason it is inevitable that supplies of vaccine should be available. A vaccine from heat sensitive strains is offered which is obtained from cell cultures."}
{"id": "PMID:232249", "title": "Heterogeneity of neoplastic cells derived from a hamster tumor induced by avian sarcoma virus B77.", "content": "Cells derived from a hamster tumor induced by avian sarcoma virus Bratislava 77 (B77) in vivo, were cultivated in vitro. After few passages two morphologically different cell lines were isolated from the parental culture (B77/H). One cell line consisted of fibroblastic cells (B77/H/fi and the other from epithelioid cells (B77/H/ep). Cells of both lines were highly tumorigenic in neonatal syngeneic hamsters, B77/H/ep cells were able to form colonies in soft agar and contained complete integrated B77 viral genome. In contrast, the B77/H/fi cells grew poorly in soft agar and did not contained B77 virus genome.", "contents": "Heterogeneity of neoplastic cells derived from a hamster tumor induced by avian sarcoma virus B77. Cells derived from a hamster tumor induced by avian sarcoma virus Bratislava 77 (B77) in vivo, were cultivated in vitro. After few passages two morphologically different cell lines were isolated from the parental culture (B77/H). One cell line consisted of fibroblastic cells (B77/H/fi and the other from epithelioid cells (B77/H/ep). Cells of both lines were highly tumorigenic in neonatal syngeneic hamsters, B77/H/ep cells were able to form colonies in soft agar and contained complete integrated B77 viral genome. In contrast, the B77/H/fi cells grew poorly in soft agar and did not contained B77 virus genome."}
{"id": "PMID:232250", "title": "Calf serum- and cell surface proteins released from cultured avian sarcoma virus-transformed and untransformed rat fibroblasts.", "content": "Cell surface and calf serum proteins were released in vitro from cultured virus-transformed, chemically transformed and normal rat embryo fibroblasts in 0.2 M urea containing serum-free culture medium. Fibronectin (LETS protein) was found in considerably higher amount in medium from normal rat embryo fibroblasts than in that from transformed cells. Major calf serum protein released from cultured normal and transformed rat cells corresponded by its electrophoretic mobility to calf serum albumin. No substantial differences in electrophoretic patterns of calf serum proteins released from normal and transformed cells into the medium were found. Time course of release of serum proteins from cell surface was measured quantitatively with the aid of radioiodinated Staphylococcus aureus protein A radioimmune assay. More than 50% of cell bound calf serum proteins remained on cell surface after 24 hours of incubation in serum-free medium.", "contents": "Calf serum- and cell surface proteins released from cultured avian sarcoma virus-transformed and untransformed rat fibroblasts. Cell surface and calf serum proteins were released in vitro from cultured virus-transformed, chemically transformed and normal rat embryo fibroblasts in 0.2 M urea containing serum-free culture medium. Fibronectin (LETS protein) was found in considerably higher amount in medium from normal rat embryo fibroblasts than in that from transformed cells. Major calf serum protein released from cultured normal and transformed rat cells corresponded by its electrophoretic mobility to calf serum albumin. No substantial differences in electrophoretic patterns of calf serum proteins released from normal and transformed cells into the medium were found. Time course of release of serum proteins from cell surface was measured quantitatively with the aid of radioiodinated Staphylococcus aureus protein A radioimmune assay. More than 50% of cell bound calf serum proteins remained on cell surface after 24 hours of incubation in serum-free medium."}
{"id": "PMID:232251", "title": "Study of the avian sarcoma virus infection of chemically transformed cells.", "content": "BHK-21/13 cells transformed with various chemical carcinogens and mutagens were tested for susceptibility to avian sarcoma virus infection. The chemically transformed BHK cells were highly tumorigenic. The treatment of these cells in vitro with avian sarcoma virus strain Schmidt-Ruppin D resulted in chemically transformed and viral infected cells with different rescuability of the integrated virus genome. The different rescuability is not due to the difference in virus penetration as was shown by vesicular stomatitis virus Schmidt-Ruppin virus pseudotype VSV(SR-D) technique. The sarcoma virus genome in the doubly transformed cells was not inducible by various virus inducers.", "contents": "Study of the avian sarcoma virus infection of chemically transformed cells. BHK-21/13 cells transformed with various chemical carcinogens and mutagens were tested for susceptibility to avian sarcoma virus infection. The chemically transformed BHK cells were highly tumorigenic. The treatment of these cells in vitro with avian sarcoma virus strain Schmidt-Ruppin D resulted in chemically transformed and viral infected cells with different rescuability of the integrated virus genome. The different rescuability is not due to the difference in virus penetration as was shown by vesicular stomatitis virus Schmidt-Ruppin virus pseudotype VSV(SR-D) technique. The sarcoma virus genome in the doubly transformed cells was not inducible by various virus inducers."}
{"id": "PMID:232252", "title": "Sero-epidemiologic study of the Epstein--Barr virus infectivity in a healthy Cuban population.", "content": "The indirect immunofluorescence test was used to study the level of humoral antibodies against viral capsid antigen of the Epstein--Barr virus (VCA-EBV), and early antigen (EA) in the sera of 322 healthy donors of the Havana City province. The age of donors ranged from several months up to 95 years. The results obtained indicate that the healthy population of Cuba is infected by EBV as well as in other countries, even though the spread and the course of infection have its specific characteristics. In the early childhood population group (3--4 years old) the infection is relatively more frequent (73%) than in adults (62--77%), despite the fact that the country is located in the tropical zone. In all the studied age groups the geometric mean titers (GMT) of antibodies were found to be lower in comparison with the other populations studied. The increase of EBV-antibody levels in the group of donors above 55 years of age, together with a large number of seropositive individuals, increase in the number of persons with high anti-VCA-EBV antibody titers (1 : 160), agrees with the results obtained by other investigators. This may be associated with some form of depression of cell-mediated immune response. Infectious mononucleosis-morbidity in the studied age groups was found to be low in 3--4-year- and 15--19-year-old age groups, where higher levels of antibodies against EA of EBV were found.", "contents": "Sero-epidemiologic study of the Epstein--Barr virus infectivity in a healthy Cuban population. The indirect immunofluorescence test was used to study the level of humoral antibodies against viral capsid antigen of the Epstein--Barr virus (VCA-EBV), and early antigen (EA) in the sera of 322 healthy donors of the Havana City province. The age of donors ranged from several months up to 95 years. The results obtained indicate that the healthy population of Cuba is infected by EBV as well as in other countries, even though the spread and the course of infection have its specific characteristics. In the early childhood population group (3--4 years old) the infection is relatively more frequent (73%) than in adults (62--77%), despite the fact that the country is located in the tropical zone. In all the studied age groups the geometric mean titers (GMT) of antibodies were found to be lower in comparison with the other populations studied. The increase of EBV-antibody levels in the group of donors above 55 years of age, together with a large number of seropositive individuals, increase in the number of persons with high anti-VCA-EBV antibody titers (1 : 160), agrees with the results obtained by other investigators. This may be associated with some form of depression of cell-mediated immune response. Infectious mononucleosis-morbidity in the studied age groups was found to be low in 3--4-year- and 15--19-year-old age groups, where higher levels of antibodies against EA of EBV were found."}
{"id": "PMID:232257", "title": "Endogenous opiates: through 1978.", "content": "The discovery of receptors in the brain for opiates and the structure of the endogenous peptides for these receptors has led to an explosion of interest in this field. The present review is the first of an annual series. It summarizes many of the highlights of research with opiate peptides published with a date of 1978 or earlier.", "contents": "Endogenous opiates: through 1978. The discovery of receptors in the brain for opiates and the structure of the endogenous peptides for these receptors has led to an explosion of interest in this field. The present review is the first of an annual series. It summarizes many of the highlights of research with opiate peptides published with a date of 1978 or earlier."}
{"id": "PMID:232275", "title": "[Peripheral nerve injuries following implantation of total endoprosthesis in the hip joint and their treatment].", "content": "The complication rate after 844 implantations of total endoprosthesis in the hip-joint, in the form of postoperative nerve injuries was found to be about 1 per cent. A number of causes may be responsible for nerve lesions, and some of these may be eliminated with a sparing operative technique. Although there are good prospects for the disappearance of paralytic symptoms, meaningful pysiotherapeutic after-care is very important. In the paralytic stage consistent exponential electrotherapy is recommended, and for recurring voluntary mobility active exercises against resistance. This will greatly improve the functional result of an operation with regard to nerve lesions.", "contents": "[Peripheral nerve injuries following implantation of total endoprosthesis in the hip joint and their treatment]. The complication rate after 844 implantations of total endoprosthesis in the hip-joint, in the form of postoperative nerve injuries was found to be about 1 per cent. A number of causes may be responsible for nerve lesions, and some of these may be eliminated with a sparing operative technique. Although there are good prospects for the disappearance of paralytic symptoms, meaningful pysiotherapeutic after-care is very important. In the paralytic stage consistent exponential electrotherapy is recommended, and for recurring voluntary mobility active exercises against resistance. This will greatly improve the functional result of an operation with regard to nerve lesions."}
{"id": "PMID:232276", "title": "[A study through factor analysis of the connection between 7 variables concerning blood lipides, with a particular reference to the interpretation of the lipidograms (author's transl)].", "content": "The AA. examined 7 variables concerning blood lipides and studied their internal relationship by means of a method, the Factor Analysis, which aims at determining the least amount of Common Factors which can sum up the information contained in the same variables. In this case three Common Factors (F) could be obtained, two of which were connected to the interpretation of the data of the lipidogram. The AA. discuss the signification of the determined Factors; they have even calculated the scores of the same Factors for each single individual and derived from the frequence distributions of the scores of F1 and F2 the normal values of the same Factors.", "contents": "[A study through factor analysis of the connection between 7 variables concerning blood lipides, with a particular reference to the interpretation of the lipidograms (author's transl)]. The AA. examined 7 variables concerning blood lipides and studied their internal relationship by means of a method, the Factor Analysis, which aims at determining the least amount of Common Factors which can sum up the information contained in the same variables. In this case three Common Factors (F) could be obtained, two of which were connected to the interpretation of the data of the lipidogram. The AA. discuss the signification of the determined Factors; they have even calculated the scores of the same Factors for each single individual and derived from the frequence distributions of the scores of F1 and F2 the normal values of the same Factors."}
{"id": "PMID:232278", "title": "[Behavior of phosphoisomerase and lactate dehydrogenase in pediatric oncological pathology].", "content": "Two glycolytic enzymes, PHI and LDH, have been evaluated in 18 children affected by leukemia or solid tumors: 11 patients had just initiated therapy, 3 patients were about to initiate therapy, while 4 patients were out of therapy. The analysis of the data obtained has shown a good correlation with the course of the disease: we have found values above the normal range in patients with a favorable course of the disease (bone marrow relapse or CNS involvement in leukemic children; relapse or metastasis in solid tumors) almost always before it was possible to demonstrate by clinical and laboratory studies the inhanchement of tumoral cells growth. This was true in all patients except two children affected by neuroblastoma, who were in a favorable immunological status (presence in the serum of free specific antibodies), and who were out of therapy. In these patients the abnormal high values of PHI were interpretated as an index of necrotic phenomena of micrometastasis of tumor cells induced by specific committed T-lymphocytes. Values of PHI and LDH in the normal range were found in patients whose disease demonstrated a favorable course. The AA. suggest the introduction of these enzymatic parameters which may be a useful index of the efficacy of the chemotherapy in the follow-up of oncologic patients.", "contents": "[Behavior of phosphoisomerase and lactate dehydrogenase in pediatric oncological pathology]. Two glycolytic enzymes, PHI and LDH, have been evaluated in 18 children affected by leukemia or solid tumors: 11 patients had just initiated therapy, 3 patients were about to initiate therapy, while 4 patients were out of therapy. The analysis of the data obtained has shown a good correlation with the course of the disease: we have found values above the normal range in patients with a favorable course of the disease (bone marrow relapse or CNS involvement in leukemic children; relapse or metastasis in solid tumors) almost always before it was possible to demonstrate by clinical and laboratory studies the inhanchement of tumoral cells growth. This was true in all patients except two children affected by neuroblastoma, who were in a favorable immunological status (presence in the serum of free specific antibodies), and who were out of therapy. In these patients the abnormal high values of PHI were interpretated as an index of necrotic phenomena of micrometastasis of tumor cells induced by specific committed T-lymphocytes. Values of PHI and LDH in the normal range were found in patients whose disease demonstrated a favorable course. The AA. suggest the introduction of these enzymatic parameters which may be a useful index of the efficacy of the chemotherapy in the follow-up of oncologic patients."}
{"id": "PMID:232283", "title": "Evidence for 6-keto-PGF1 alpha in adrenal cortex of the rat and effects of 6-keto-PGF1 alpha and PGI2 on adrenal cAMP levels and steroidogenesis.", "content": "Both intact cortical tissue and isolated cortical cells from the adrenal gland of the rat were analyzed for 6-keto-PGF1 alpha, the hydrolysis metabolite of PGI2, using high-performance liquid chromatography and gas chromatography-mass spectrometry. 6-Keto-PGF1 alpha was present in both incubations of intact tissue and isolated cells of the adrenal cortex, at higher concentrations than either PGF2 alpha or PGE2. Thus, the cortex does not depend upon vascular components for the synthesis of the PGI2 metabolite. Studies in vitro, using isolated cortical cells exposed to 6-keto-PGF1 alpha (10(-6)-10(-4)M), show that this PG does not alter cAMP levels or steroidogenesis. Cells exposed to PGI2 (10(-6)-10(-4)M), however, show a concentration-dependent increase of up to 4-fold in the levels of cAMP without altering cortico-sterone production, ACTH (5-200 microU/ml) increased cAMP levels up to 14-fold, and corticosterone levels up to 6-fold, in isolated cells. ACTH plus PGI2 produced an additive increase in levels of cAMP, however, the steroidogenic response was equal to that elicited by ACTH alone. Adrenal glands of the rat perfused in situ with PGI2 showed a small decrease in corticosterone production, whereas ACTH greatly stimulated steroid release. Thus, while 6-keto-PGF1 alpha is present in the rat adrenal cortex, its precursor, PGI2, is not a steroidogenic agent in this tissue although it does stimulate the accumulation of cAMP.", "contents": "Evidence for 6-keto-PGF1 alpha in adrenal cortex of the rat and effects of 6-keto-PGF1 alpha and PGI2 on adrenal cAMP levels and steroidogenesis. Both intact cortical tissue and isolated cortical cells from the adrenal gland of the rat were analyzed for 6-keto-PGF1 alpha, the hydrolysis metabolite of PGI2, using high-performance liquid chromatography and gas chromatography-mass spectrometry. 6-Keto-PGF1 alpha was present in both incubations of intact tissue and isolated cells of the adrenal cortex, at higher concentrations than either PGF2 alpha or PGE2. Thus, the cortex does not depend upon vascular components for the synthesis of the PGI2 metabolite. Studies in vitro, using isolated cortical cells exposed to 6-keto-PGF1 alpha (10(-6)-10(-4)M), show that this PG does not alter cAMP levels or steroidogenesis. Cells exposed to PGI2 (10(-6)-10(-4)M), however, show a concentration-dependent increase of up to 4-fold in the levels of cAMP without altering cortico-sterone production, ACTH (5-200 microU/ml) increased cAMP levels up to 14-fold, and corticosterone levels up to 6-fold, in isolated cells. ACTH plus PGI2 produced an additive increase in levels of cAMP, however, the steroidogenic response was equal to that elicited by ACTH alone. Adrenal glands of the rat perfused in situ with PGI2 showed a small decrease in corticosterone production, whereas ACTH greatly stimulated steroid release. Thus, while 6-keto-PGF1 alpha is present in the rat adrenal cortex, its precursor, PGI2, is not a steroidogenic agent in this tissue although it does stimulate the accumulation of cAMP."}
{"id": "PMID:232293", "title": "Assay of mitochondrial membrane-bound enzyme activities in the presence of triton X-100.", "content": "Mitochondrial ATPase and cytochrome c oxidase activities are not severely affected by Triton X-100 concentrations between 0.1 and 2.0% (w/v). The former is solubilized by the effect of the detergent, while the latter is not. Succinate: cytochrome c reductase and rotenone-sensitive NADH: cytochrome c reductase activities are destroyed even a low detergent concentrations. Succinate:coenzyme Q oxidoreductase is affected by the surfactant in a more complex way, so that selective solubilization of some subunit(s) could be involved.", "contents": "Assay of mitochondrial membrane-bound enzyme activities in the presence of triton X-100. Mitochondrial ATPase and cytochrome c oxidase activities are not severely affected by Triton X-100 concentrations between 0.1 and 2.0% (w/v). The former is solubilized by the effect of the detergent, while the latter is not. Succinate: cytochrome c reductase and rotenone-sensitive NADH: cytochrome c reductase activities are destroyed even a low detergent concentrations. Succinate:coenzyme Q oxidoreductase is affected by the surfactant in a more complex way, so that selective solubilization of some subunit(s) could be involved."}
{"id": "PMID:232294", "title": "Conversion of (U-14C)-glycerol, (2-3H)-glycerol and (1-14C)-palmitate into circulating lipoproteins in the rat.", "content": "The in vivo formation of labelled very low density lipoproteins (VLDL) from (U-14C)-glycerol, (2-3H)-glycerol and (1-14C)-palmitate was studied in fed female rats. The rate of disappearance of radioactivity from plasma after the i.v. injection with these tracers was similar for (U-14C)-glycerol and (1-14C)-palmitate. With (2-3H)-glycerol, plasma radioactivity at 10 min was lower than with the other substrates although it did not change thereafter. A certain proportion of radioactivity administered as glycerol appeared in plasma lipids, mainly in the VLDL glyceride glycerol fraction, although when (U-14C)-glycerol was the substrate, a considerable portion also appeared in the esterified fatty acids of these lipoproteins. When using (1-14C)-palmitate, practically all the circulating labelled esterified fatty acids appeared in the VLDL fraction, while the labelled free fatty acids appeared in lipoprotein of higher density, presumable free fatty acid-albumin complexes. This data is discussed in terms of the role of the liver in the rapid, continuous cycling of these substrates to yield VLDL-glycerides for their extrahepatic utilization.", "contents": "Conversion of (U-14C)-glycerol, (2-3H)-glycerol and (1-14C)-palmitate into circulating lipoproteins in the rat. The in vivo formation of labelled very low density lipoproteins (VLDL) from (U-14C)-glycerol, (2-3H)-glycerol and (1-14C)-palmitate was studied in fed female rats. The rate of disappearance of radioactivity from plasma after the i.v. injection with these tracers was similar for (U-14C)-glycerol and (1-14C)-palmitate. With (2-3H)-glycerol, plasma radioactivity at 10 min was lower than with the other substrates although it did not change thereafter. A certain proportion of radioactivity administered as glycerol appeared in plasma lipids, mainly in the VLDL glyceride glycerol fraction, although when (U-14C)-glycerol was the substrate, a considerable portion also appeared in the esterified fatty acids of these lipoproteins. When using (1-14C)-palmitate, practically all the circulating labelled esterified fatty acids appeared in the VLDL fraction, while the labelled free fatty acids appeared in lipoprotein of higher density, presumable free fatty acid-albumin complexes. This data is discussed in terms of the role of the liver in the rapid, continuous cycling of these substrates to yield VLDL-glycerides for their extrahepatic utilization."}
{"id": "PMID:232295", "title": "Phosphatase activity in avian mycoplasmas.", "content": "Fifty-four strains of avian mycoplasma representing 11 species or serotypes were examined for their phosphatase activity using two different methods. Both methods gave similar results. All of four strains of Mycoplasma anatis and six of M meleagridis and the type strain of serotype L were phosphatase positive. The other species gave variable reactions between strains and on different occasions of testing.", "contents": "Phosphatase activity in avian mycoplasmas. Fifty-four strains of avian mycoplasma representing 11 species or serotypes were examined for their phosphatase activity using two different methods. Both methods gave similar results. All of four strains of Mycoplasma anatis and six of M meleagridis and the type strain of serotype L were phosphatase positive. The other species gave variable reactions between strains and on different occasions of testing."}
{"id": "PMID:232297", "title": "Effect of serum and blood on Enterobacteriaceae grown in the presence of subminimal inhibitory concentrations of ampicillin and mecillinam.", "content": "Bacteria from the strains of five species of Enterobacteriaceae grown in the presence of subminimal inhibitory concentrations of ampicillin or mecillinam formed into filamentous or round cells. These filamentous and round cells as well as normal control bacteria were incubated with either fresh human serum or blood, the bactericidal effects of which were then determined. In most cases, the bactericidal effect of either serum or blood on filamentous or round cells was less than the effect on control cells. In some cases, the effect on these drug-exposed cells was similar to that on control cells, but in no instance was the effect greater for the drug-exposed cells than for the control cells. However, in all cases in which the bactericidal effect of either serum or blood on the control cells was greater than or equal to 99%, the bactericidal effect on the drug-exposed cells was close to 90%. Although drug-exposed cells were not much more resistant to the bactericidal effect of serum or blood than were normal bacteria, they clearly were not more susceptible to these effects.", "contents": "Effect of serum and blood on Enterobacteriaceae grown in the presence of subminimal inhibitory concentrations of ampicillin and mecillinam. Bacteria from the strains of five species of Enterobacteriaceae grown in the presence of subminimal inhibitory concentrations of ampicillin or mecillinam formed into filamentous or round cells. These filamentous and round cells as well as normal control bacteria were incubated with either fresh human serum or blood, the bactericidal effects of which were then determined. In most cases, the bactericidal effect of either serum or blood on filamentous or round cells was less than the effect on control cells. In some cases, the effect on these drug-exposed cells was similar to that on control cells, but in no instance was the effect greater for the drug-exposed cells than for the control cells. However, in all cases in which the bactericidal effect of either serum or blood on the control cells was greater than or equal to 99%, the bactericidal effect on the drug-exposed cells was close to 90%. Although drug-exposed cells were not much more resistant to the bactericidal effect of serum or blood than were normal bacteria, they clearly were not more susceptible to these effects."}
{"id": "PMID:232298", "title": "Drug-inactivating enzymes of bacteria grown in subminimal inhibitory concentrations of antibiotics.", "content": "Repeated transfers of strains of Escherichia coli and Staphylococcus aureus in medium containing subminimal inhibitory concentrations (sub-MICs) of gentamicin caused a moderate increase in the minimal inhibitory concentration of gentamicin. At the end of such transfers, E. coli K12 produced aminoglycoside phosphotransferase(3')-I [APH(3')], AND E. coli R112, which carries the plasmid-coded enzyme APH(3')-I, also produced the acetylating enzyme aminoglycoside acetyltransferase(2') [AAC(2')]. E. coli R148, which produces aminoglycoside phosphotransferase(3')-II [APH(3')-II], did not change its output of enzymes. Repeated transfers to media containing increasing concentrations of gentamicin resulted in the development of complete resistance to all aminoglycosides without the concurrent development of any demonstrable new enzyme activity. With repeated transfers in drug-free medium, a complete reversal to susceptibility to gentamicin, but not to other aminoglycosides, was obtained for strains that had previously been transferred in sub-MICs of gentamicin, whereas strains that had been transferred in increasing concentrations of gentamicin did not revert to their original sensitivity to aminoglycosides despite repeated transfers in drug-free medium.", "contents": "Drug-inactivating enzymes of bacteria grown in subminimal inhibitory concentrations of antibiotics. Repeated transfers of strains of Escherichia coli and Staphylococcus aureus in medium containing subminimal inhibitory concentrations (sub-MICs) of gentamicin caused a moderate increase in the minimal inhibitory concentration of gentamicin. At the end of such transfers, E. coli K12 produced aminoglycoside phosphotransferase(3')-I [APH(3')], AND E. coli R112, which carries the plasmid-coded enzyme APH(3')-I, also produced the acetylating enzyme aminoglycoside acetyltransferase(2') [AAC(2')]. E. coli R148, which produces aminoglycoside phosphotransferase(3')-II [APH(3')-II], did not change its output of enzymes. Repeated transfers to media containing increasing concentrations of gentamicin resulted in the development of complete resistance to all aminoglycosides without the concurrent development of any demonstrable new enzyme activity. With repeated transfers in drug-free medium, a complete reversal to susceptibility to gentamicin, but not to other aminoglycosides, was obtained for strains that had previously been transferred in sub-MICs of gentamicin, whereas strains that had been transferred in increasing concentrations of gentamicin did not revert to their original sensitivity to aminoglycosides despite repeated transfers in drug-free medium."}
{"id": "PMID:232302", "title": "[Effectiveness of treatment with rifampicin and isoniazid in association with ethambutol or prothionamide in patients with recently detected pulmonary tuberculosis].", "content": "In newly discovered patients with cavitary forms of pulmonary tuberculosis treatment with rifampicin, in association with other drugs, leads to recovery (negativation) in 69,6 percent of the patients in 3 months, in 92 per cent after 6 months and in 94,6 percent after 9 months of treatment. Closure of cavities is found in 23,4 percent, 64,5 percent and 76,6 percent of all patients at the corresponding time intervals. Comparisons of the various regimens of chemotherapy which include rifampicin showed that the maximal efficiency was obtained with rifampicin, ioniazid and a third drug (either etambutol or protionamide). The time intervals for the disappearence of bacilli and for the closure of cavities depend to a great extent on the degree of development of the pathological process, on the type of the lesions and the intensity of bacilli elimination at the start of the treatment. The use of rifampicin in new patients, in association with other drugs, leads to a rapid negativation, a shortening of the time necessary for the closure of cavities, especially in patients in whom the disappearence of the bacilli from the sputum occurs in the first three months.", "contents": "[Effectiveness of treatment with rifampicin and isoniazid in association with ethambutol or prothionamide in patients with recently detected pulmonary tuberculosis]. In newly discovered patients with cavitary forms of pulmonary tuberculosis treatment with rifampicin, in association with other drugs, leads to recovery (negativation) in 69,6 percent of the patients in 3 months, in 92 per cent after 6 months and in 94,6 percent after 9 months of treatment. Closure of cavities is found in 23,4 percent, 64,5 percent and 76,6 percent of all patients at the corresponding time intervals. Comparisons of the various regimens of chemotherapy which include rifampicin showed that the maximal efficiency was obtained with rifampicin, ioniazid and a third drug (either etambutol or protionamide). The time intervals for the disappearence of bacilli and for the closure of cavities depend to a great extent on the degree of development of the pathological process, on the type of the lesions and the intensity of bacilli elimination at the start of the treatment. The use of rifampicin in new patients, in association with other drugs, leads to a rapid negativation, a shortening of the time necessary for the closure of cavities, especially in patients in whom the disappearence of the bacilli from the sputum occurs in the first three months."}
{"id": "PMID:232305", "title": "[Immunoglobulins in clear-fluid pleurisy (preliminary note)].", "content": "The study of IgG, IgM and IgA immunoglobulins in the pleural exsudate and in the serum of 34 patients with pleurisy of various etiologies shows an increase in the level of serum immunoglobulins as compared with the level in the exsudate. The only immunoglobulin fraction showing variations in relation with the etiology of the disease in the IgG fraction, which is increased in inflammatory exsudates, in contrast with those found in pulmonary cancers. Recovery without sequellae of pleurisy supposes the presence (in situ) of an increased amount of IgG. These observations are supported by a good statistical-mathematical correlation (p less than 0,01 and 0,001).", "contents": "[Immunoglobulins in clear-fluid pleurisy (preliminary note)]. The study of IgG, IgM and IgA immunoglobulins in the pleural exsudate and in the serum of 34 patients with pleurisy of various etiologies shows an increase in the level of serum immunoglobulins as compared with the level in the exsudate. The only immunoglobulin fraction showing variations in relation with the etiology of the disease in the IgG fraction, which is increased in inflammatory exsudates, in contrast with those found in pulmonary cancers. Recovery without sequellae of pleurisy supposes the presence (in situ) of an increased amount of IgG. These observations are supported by a good statistical-mathematical correlation (p less than 0,01 and 0,001)."}
{"id": "PMID:232306", "title": "[Current aspects of recovery and invalidism in recurrent pulmonary tuberculosis].", "content": "An analysis was made, 12 months after strictly supervised treatment which included rifampicin and/or etambutol, of 83 cases of relapses of pulmonary tuberculosis. Therapeutic aspects were studied, as well as problems in relation to the possibility to continue work, as well as temporary invalidity. The therapeutic curing of the relapses was achieved in 74 patients (89,15 percent), while 9 remained with a positive bK in the sputum. The recovered subjects continued their activity without any changes in the working place, and retirement was accepted for active tuberculosis in 12,5 percent of the patients, while retirement for posttuberculous syndrome in another 7,14 percent of the patients. Males were predominant (81,81 percent of the total), mostly aged between 30 and 49 years, originating from rural environments.", "contents": "[Current aspects of recovery and invalidism in recurrent pulmonary tuberculosis]. An analysis was made, 12 months after strictly supervised treatment which included rifampicin and/or etambutol, of 83 cases of relapses of pulmonary tuberculosis. Therapeutic aspects were studied, as well as problems in relation to the possibility to continue work, as well as temporary invalidity. The therapeutic curing of the relapses was achieved in 74 patients (89,15 percent), while 9 remained with a positive bK in the sputum. The recovered subjects continued their activity without any changes in the working place, and retirement was accepted for active tuberculosis in 12,5 percent of the patients, while retirement for posttuberculous syndrome in another 7,14 percent of the patients. Males were predominant (81,81 percent of the total), mostly aged between 30 and 49 years, originating from rural environments."}
{"id": "PMID:232310", "title": "A rapid method for the separation of functional lymphoid cell populations of human and animal origin on PVP-silica (Percoll) density gradients.", "content": "Subclasses of lymphocytes can be separated on gradients of non-toxic polyvinylpyrrolidone-coated colloidal silica (Percoll) by virtue of differential densities. Such gradients can yield functionally active lymphocyte populations after brief centrifugation. Gradients can be generated in a discontinuous step fashion and centrifuged in standard table-top laboratory centrifuges or as self-generating gradients during ultracentrifugation. The density medium has low viscosity and can be made isotonic for virtually any use. Gradients have proved useful in both human and experimental animal studies, and high percentage yields allow  for separations from small cell numbers. Methods are described for separation of whole blood and lymphoid subpopuctions. The cytoxic capability of various density fractions was evaluated for mixed lymphocyte culture-induced allogeneic killing and spontaneous, so-called \"natural\" killer cell activity. The lower density associated with blast transformation allows for significant enrichments of stimulated cells from in vitro cultures. Higher thymidine incorporation, restimualtion in mixed lymphocyte reactions, and greater cytotoxic capacity are associated with these \"blast\" fractions.", "contents": "A rapid method for the separation of functional lymphoid cell populations of human and animal origin on PVP-silica (Percoll) density gradients. Subclasses of lymphocytes can be separated on gradients of non-toxic polyvinylpyrrolidone-coated colloidal silica (Percoll) by virtue of differential densities. Such gradients can yield functionally active lymphocyte populations after brief centrifugation. Gradients can be generated in a discontinuous step fashion and centrifuged in standard table-top laboratory centrifuges or as self-generating gradients during ultracentrifugation. The density medium has low viscosity and can be made isotonic for virtually any use. Gradients have proved useful in both human and experimental animal studies, and high percentage yields allow  for separations from small cell numbers. Methods are described for separation of whole blood and lymphoid subpopuctions. The cytoxic capability of various density fractions was evaluated for mixed lymphocyte culture-induced allogeneic killing and spontaneous, so-called \"natural\" killer cell activity. The lower density associated with blast transformation allows for significant enrichments of stimulated cells from in vitro cultures. Higher thymidine incorporation, restimualtion in mixed lymphocyte reactions, and greater cytotoxic capacity are associated with these \"blast\" fractions."}
{"id": "PMID:232313", "title": "The interaction of cadmium-binding proteins (Cd-bp) and progesterone in cadmium-induced tissue and embryo toxicity.", "content": "Previous work indicates that a dimer of Cd-thionein (Cd-bp-D, 19,000 MW) is involved in the hereditary resistance to Cd-embryotoxicity seen in the inbred NAW/Pr (NAW) mouse strain. Cd-bp-D is not detected in virgin females after Cd exposure and is detected only after the first 24 hours of exposure to Cd in an inbred strain (C57BL/10ChPr) susceptible to Cd-induced embryotoxicity (Wolkowski, '74; Wolkowski-Tyl, '78). Since progesterone (P) is critical for maintenance of pregnancy in mice, we have studied the possible relationship between this hormone and Cd-bp-D production. As a model system, was examined effects of Cd treatment on Cd-bp synthesis in NAW males. It was anticipated that this model could provide information bearing not only on the relationship between P and Cd-bp-D production, but also on that between Cd-bp-D and Cd toxicity, since a single sc injection of CdCl2 causes typical testicular hemorrhagic necrosis in NAW males, and these animals make only metallothionein and not Cd-bp-D. NAW males were, therefore, given P (0.1 g/Kg bw) and then exposed to Cd. Sephadex gel chromatography (G-200) of liver cytosol from animals killed 24 hours later detected only Cd-bp-D. Testes of these males did not show hemorrhagic necrosis. Since the adrenals of male mammals release P in response to stress, NAW males were stressed by repeated sesame oil or propylene glycol injections (5 ml/Kg bw), or the adrenal was stimulated directly with injections of ACTH (100 IU/Kg bw) for seven days prior to Cd exposure. All methods tested which significantly elevated serum P levels (as confirmed by radioimmunoassay), also resulted in production of Cd-bp-D and absence of testicular hemorrhage in Cd-treated NAW males. Suppression of P release by injection of dexamethazone or corticosterone or by adrenalectomy resulted in testicular hemorrhage and production of only metalicthionein after Cd exposure. The relevance of the interaction between P, Cd-bp-D and protection against Cd-induced toxicity seen in the model system was supported by analysis of serum P levels in pregnant females; elevated levels were seen in resistant (NAW dams on day 10 of gestation and significantly lower levels seen in dams from a Cd-sensitive strain.", "contents": "The interaction of cadmium-binding proteins (Cd-bp) and progesterone in cadmium-induced tissue and embryo toxicity. Previous work indicates that a dimer of Cd-thionein (Cd-bp-D, 19,000 MW) is involved in the hereditary resistance to Cd-embryotoxicity seen in the inbred NAW/Pr (NAW) mouse strain. Cd-bp-D is not detected in virgin females after Cd exposure and is detected only after the first 24 hours of exposure to Cd in an inbred strain (C57BL/10ChPr) susceptible to Cd-induced embryotoxicity (Wolkowski, '74; Wolkowski-Tyl, '78). Since progesterone (P) is critical for maintenance of pregnancy in mice, we have studied the possible relationship between this hormone and Cd-bp-D production. As a model system, was examined effects of Cd treatment on Cd-bp synthesis in NAW males. It was anticipated that this model could provide information bearing not only on the relationship between P and Cd-bp-D production, but also on that between Cd-bp-D and Cd toxicity, since a single sc injection of CdCl2 causes typical testicular hemorrhagic necrosis in NAW males, and these animals make only metallothionein and not Cd-bp-D. NAW males were, therefore, given P (0.1 g/Kg bw) and then exposed to Cd. Sephadex gel chromatography (G-200) of liver cytosol from animals killed 24 hours later detected only Cd-bp-D. Testes of these males did not show hemorrhagic necrosis. Since the adrenals of male mammals release P in response to stress, NAW males were stressed by repeated sesame oil or propylene glycol injections (5 ml/Kg bw), or the adrenal was stimulated directly with injections of ACTH (100 IU/Kg bw) for seven days prior to Cd exposure. All methods tested which significantly elevated serum P levels (as confirmed by radioimmunoassay), also resulted in production of Cd-bp-D and absence of testicular hemorrhage in Cd-treated NAW males. Suppression of P release by injection of dexamethazone or corticosterone or by adrenalectomy resulted in testicular hemorrhage and production of only metalicthionein after Cd exposure. The relevance of the interaction between P, Cd-bp-D and protection against Cd-induced toxicity seen in the model system was supported by analysis of serum P levels in pregnant females; elevated levels were seen in resistant (NAW dams on day 10 of gestation and significantly lower levels seen in dams from a Cd-sensitive strain."}
{"id": "PMID:232314", "title": "Small cell carcinoma: combined approach to treatment.", "content": "Fifty-six patients with untreated small cell carcinoma of the bronchus were treated with three courses of chemotherapy (cyclophosphamide, vincristine, and procarbazine and methotrexate) and assessed for response. Thirty-one patients (55.4%) were classified as responders; they were given a course of radiotherapy and were then randomly allocated to continued cyclical chemotherapy or not further chemotherapy until relapse. Non-responders to chemotherapy were treated with radiotherapy or palliatively. The median survival was 10.5 months in responders and 6 months in non-responders (P less than 0.01). The one-year survival in responders was 42%. There was no statistical difference in survival between patients treated with continued chemotherapy and those treated at relapse. Sixty-nine per cent of patients experienced no side effects from chemotherapy. Three indicators of non-response to chemotherapy were identified--exercise tolerance at diagnosis, macroscopic liver metastases, and inappropriate ADH secretion.", "contents": "Small cell carcinoma: combined approach to treatment. Fifty-six patients with untreated small cell carcinoma of the bronchus were treated with three courses of chemotherapy (cyclophosphamide, vincristine, and procarbazine and methotrexate) and assessed for response. Thirty-one patients (55.4%) were classified as responders; they were given a course of radiotherapy and were then randomly allocated to continued cyclical chemotherapy or not further chemotherapy until relapse. Non-responders to chemotherapy were treated with radiotherapy or palliatively. The median survival was 10.5 months in responders and 6 months in non-responders (P less than 0.01). The one-year survival in responders was 42%. There was no statistical difference in survival between patients treated with continued chemotherapy and those treated at relapse. Sixty-nine per cent of patients experienced no side effects from chemotherapy. Three indicators of non-response to chemotherapy were identified--exercise tolerance at diagnosis, macroscopic liver metastases, and inappropriate ADH secretion."}
{"id": "PMID:232316", "title": "Platelet function and serum high density lipoproteins.", "content": "Two groups of healthy male subjects one with low (mean 1.03 mmol/l), and the other with normal (mean 1.80 mmol/l), concentrations of high density lipoprotein (HDL) cholesterol in plasma were investigated. A series of in vitro platelet function tests were performed in order to investigate a possible connection between low HDL concentration, which has been defined as an independent risk factor for the occurrence of CHD, and disturbances in platelet function. No significant differences in platelet function were observed between the two groups. A positive correlation was found between platelet factor 3 activity both in platelet rich and platelet poor plasma and the plasma concentration of HDL.", "contents": "Platelet function and serum high density lipoproteins. Two groups of healthy male subjects one with low (mean 1.03 mmol/l), and the other with normal (mean 1.80 mmol/l), concentrations of high density lipoprotein (HDL) cholesterol in plasma were investigated. A series of in vitro platelet function tests were performed in order to investigate a possible connection between low HDL concentration, which has been defined as an independent risk factor for the occurrence of CHD, and disturbances in platelet function. No significant differences in platelet function were observed between the two groups. A positive correlation was found between platelet factor 3 activity both in platelet rich and platelet poor plasma and the plasma concentration of HDL."}
{"id": "PMID:232317", "title": "Macrophage inhibition of collagen-induced platelet aggregation.", "content": "Collagen was incubated with cells or media fractions of mouse peritoneal macrophage cultures, and its aggregating effect on human platelets was tested. Incubation with lysates of cultured cells completely abolished the normal collagen-induced platelet aggregation, while incubation with media fractions only caused partial inhibition. The latter inhibition was more pronounced after macrophage phagocytosis of latex particles, while endocytosis of endotoxin had no effect. Corresponding macrophage cultures were also tested for specific collagenase activity, using 14C-glycine labelled collagen as substrate. Collagenase activity was found in the culture media fractions only, and the enzyme activity could be enhanced by endocytosis of latex as well as endotoxin. It appears that the effect of macrophage lysates and media on collagen-platelet interaction cannot be ascribed only to secretion of collagenase from macrophages.", "contents": "Macrophage inhibition of collagen-induced platelet aggregation. Collagen was incubated with cells or media fractions of mouse peritoneal macrophage cultures, and its aggregating effect on human platelets was tested. Incubation with lysates of cultured cells completely abolished the normal collagen-induced platelet aggregation, while incubation with media fractions only caused partial inhibition. The latter inhibition was more pronounced after macrophage phagocytosis of latex particles, while endocytosis of endotoxin had no effect. Corresponding macrophage cultures were also tested for specific collagenase activity, using 14C-glycine labelled collagen as substrate. Collagenase activity was found in the culture media fractions only, and the enzyme activity could be enhanced by endocytosis of latex as well as endotoxin. It appears that the effect of macrophage lysates and media on collagen-platelet interaction cannot be ascribed only to secretion of collagenase from macrophages."}
{"id": "PMID:232319", "title": "Effects of dithiocarb and (+)-cyanidanol-3 on the hepatotoxicity and metabolism of vinylidene chloride in rats.", "content": "The acute hepatotoxic effects of vinylidene chloride (VDC) were evidenced by measurement of the increase in the serum levels of the aminotransferase (GPT) and sorbitol dehydrogenase (SDH), hepatic glutathione (GSH) depletion and histological examinations in rats. The hepatoprotective agents dithiocarb and (+)-cyanidanol-3 proved well able to antagonize these toxic effects of VDC. While dithiocarb inhibited the in vivo metabolism of VDC in a closed exposure system, (+)-cyanidanol-3 had no influence at all. These findings substantiate the role of the microsomal monooxygenase system in the metabolism and hepatotoxicity of VDC. The mechanisms by which dithiocarb and (+)-cyanidanol-3 act as antihepatotoxic agents are different: the inhibition of the metabolic activation by dithiocarb and free radical-scavenging by (+)-cyanidanol-3.", "contents": "Effects of dithiocarb and (+)-cyanidanol-3 on the hepatotoxicity and metabolism of vinylidene chloride in rats. The acute hepatotoxic effects of vinylidene chloride (VDC) were evidenced by measurement of the increase in the serum levels of the aminotransferase (GPT) and sorbitol dehydrogenase (SDH), hepatic glutathione (GSH) depletion and histological examinations in rats. The hepatoprotective agents dithiocarb and (+)-cyanidanol-3 proved well able to antagonize these toxic effects of VDC. While dithiocarb inhibited the in vivo metabolism of VDC in a closed exposure system, (+)-cyanidanol-3 had no influence at all. These findings substantiate the role of the microsomal monooxygenase system in the metabolism and hepatotoxicity of VDC. The mechanisms by which dithiocarb and (+)-cyanidanol-3 act as antihepatotoxic agents are different: the inhibition of the metabolic activation by dithiocarb and free radical-scavenging by (+)-cyanidanol-3."}
{"id": "PMID:232322", "title": "Quantitative serum lipoprotein electrophoresis in Nigerians.", "content": "In response to the growing demand for lipid profiles in Nigerian patients with suspected ischaemic heart disease, cerebro-vascular accident and hypertension, serum lipoprotein electrophoresis based on ozone-Schiff staining technique and densitometric scanning has been developed. Out of 93 serum samples 80 showed three distinct bands in the electrophoretic patterns; nine showed two distinct bands and four had unusual migration characteristics. Mean percentages of the three bands in the common pattern were 43.5, 22.8, and 33.7 for alpha pre-beta and beta lipoproteins respectively. The relative preponderance of alpha lipoproteins in Africans contrasts with the findings in Europeans. It supports the view that high serum alpha lipoproteins may be protective against ischaemic heart disease in contrast to the atherogenic role of beta lipoproteins.", "contents": "Quantitative serum lipoprotein electrophoresis in Nigerians. In response to the growing demand for lipid profiles in Nigerian patients with suspected ischaemic heart disease, cerebro-vascular accident and hypertension, serum lipoprotein electrophoresis based on ozone-Schiff staining technique and densitometric scanning has been developed. Out of 93 serum samples 80 showed three distinct bands in the electrophoretic patterns; nine showed two distinct bands and four had unusual migration characteristics. Mean percentages of the three bands in the common pattern were 43.5, 22.8, and 33.7 for alpha pre-beta and beta lipoproteins respectively. The relative preponderance of alpha lipoproteins in Africans contrasts with the findings in Europeans. It supports the view that high serum alpha lipoproteins may be protective against ischaemic heart disease in contrast to the atherogenic role of beta lipoproteins."}
{"id": "PMID:232323", "title": "DNA and oestradiol receptor distribution in human breast cancer.", "content": "The content of DNA and oestradiol receptors was measured in two different samples taken from the same tumoral mass of 33 primary infiltrating ductal carcinomas. The results were related to the total cytoplasmic protein and to the DNA of the tissue. The results showed that variations of both DNA and oestradiol receptors are frequent and often significant. The reliability of analyses carried out on a single biopsy is discussed.", "contents": "DNA and oestradiol receptor distribution in human breast cancer. The content of DNA and oestradiol receptors was measured in two different samples taken from the same tumoral mass of 33 primary infiltrating ductal carcinomas. The results were related to the total cytoplasmic protein and to the DNA of the tissue. The results showed that variations of both DNA and oestradiol receptors are frequent and often significant. The reliability of analyses carried out on a single biopsy is discussed."}
{"id": "PMID:232324", "title": "Prolactin receptor in human mammary carcinoma.", "content": "The specific binding of labelled human prolactin was determined in 83 human breast carcinomas. Twenty-seven tumors (32.5%) contained specific binding for prolactin of at least 1% and were considered prolactin receptor positive. The binding was found linearly related to membrane protein concentration and specific only for lactogenic hormones. By Scatchard analysis the dissociation constant appeared similar to that observed in other target tissues, with a low binding capacity.", "contents": "Prolactin receptor in human mammary carcinoma. The specific binding of labelled human prolactin was determined in 83 human breast carcinomas. Twenty-seven tumors (32.5%) contained specific binding for prolactin of at least 1% and were considered prolactin receptor positive. The binding was found linearly related to membrane protein concentration and specific only for lactogenic hormones. By Scatchard analysis the dissociation constant appeared similar to that observed in other target tissues, with a low binding capacity."}
{"id": "PMID:232326", "title": "A field trial with a multicomponent inactivated respiratory viral vaccine.", "content": "An inactivated virus vaccine containing strains of parainfluenza type 3 (PI3), bovine adenovirus type 3, reovirus type 1, bovine virus diarrhoea (BVD) and infectious bovine rhinotracheitis (IBR) viruses was tested in a group of 58 calves reared in a semi-intensive management system. Following vaccination, 1/30, 14/30 and 17/30, showed significant rises in antibody titre to reovirus type 1, adenovirus type 3 and IBR respectively. None of the animals showed significant serological response to PI 3 and BVD. In the control group, 2/28, 1/28, 6/28 and 3/28 developed antibody responses to reovirus type 1, BVD, adenovirus type 3 and IBR respectively. Microbiological examination revealed the presence of a wide variety of commensal bacteria and Mycoplasma bovirhinis in both groups. Analysis of the records of clinical examinations indicated that the respiratory tract infections occurred among the calves at between 50 and 80 days after arrival at the farm, and that there was no significant difference between the test and the control groups. A number of animals had maternal antibodies to the various components of the vaccine present before the trial commenced and these antibodies appeared to interfere with the subsequent serological response to the antigen challenge. The vaccination schedule recommended by the manufacturer does not entirely circumvent this problem.", "contents": "A field trial with a multicomponent inactivated respiratory viral vaccine. An inactivated virus vaccine containing strains of parainfluenza type 3 (PI3), bovine adenovirus type 3, reovirus type 1, bovine virus diarrhoea (BVD) and infectious bovine rhinotracheitis (IBR) viruses was tested in a group of 58 calves reared in a semi-intensive management system. Following vaccination, 1/30, 14/30 and 17/30, showed significant rises in antibody titre to reovirus type 1, adenovirus type 3 and IBR respectively. None of the animals showed significant serological response to PI 3 and BVD. In the control group, 2/28, 1/28, 6/28 and 3/28 developed antibody responses to reovirus type 1, BVD, adenovirus type 3 and IBR respectively. Microbiological examination revealed the presence of a wide variety of commensal bacteria and Mycoplasma bovirhinis in both groups. Analysis of the records of clinical examinations indicated that the respiratory tract infections occurred among the calves at between 50 and 80 days after arrival at the farm, and that there was no significant difference between the test and the control groups. A number of animals had maternal antibodies to the various components of the vaccine present before the trial commenced and these antibodies appeared to interfere with the subsequent serological response to the antigen challenge. The vaccination schedule recommended by the manufacturer does not entirely circumvent this problem."}
{"id": "PMID:232325", "title": "[Influence of glutaraldehyde on Na+, K+-ATPase activity of brain tissue and enzymic preparations under conditions of electron cytochemical analysis].", "content": "The glutaraldehyde inhibitory influence on Mg2+, Na+, K+-ATPase activity of the brain tissue is shown to increase with a rise in the glutaraldehyde concentration; a direct dependence is established between the degree of inhibition and the treatment time and temperature. The glutaraldehyde inhibitory effect on the activity of the brain microsomal fraction Na+, K+-ATPase preparations under the same treatment conditions is considerably higher. A histochemical detection of the cerebral cortex Mg2+, Na+, K+-ATPase was carried out under optimal conditions of fixation, and a conclusion is made on possibility of using glutaraldehyde as a fixator in histochemical investigations.", "contents": "[Influence of glutaraldehyde on Na+, K+-ATPase activity of brain tissue and enzymic preparations under conditions of electron cytochemical analysis]. The glutaraldehyde inhibitory influence on Mg2+, Na+, K+-ATPase activity of the brain tissue is shown to increase with a rise in the glutaraldehyde concentration; a direct dependence is established between the degree of inhibition and the treatment time and temperature. The glutaraldehyde inhibitory effect on the activity of the brain microsomal fraction Na+, K+-ATPase preparations under the same treatment conditions is considerably higher. A histochemical detection of the cerebral cortex Mg2+, Na+, K+-ATPase was carried out under optimal conditions of fixation, and a conclusion is made on possibility of using glutaraldehyde as a fixator in histochemical investigations."}
{"id": "PMID:232331", "title": "[Serological diagnosis of IBR. Comparative studies of cattle sera in the virus neurtalization and passive hemagglutination reactions].", "content": "Three hundred eighty six cattle serums were simultaneously investigated by virus neutralizing (VN) and passive hemagglutination (PSH) reactions. Results obtained by the two methods coincided in 94% of the sermums studied and all serums with VN antibodies had also antibodies which can be established by the PSH reaction. About 6% of the positive reagents for PSH reaction were negative for the VN reaction. These were serums containing early antibodies (IgM) or low-titer antibodies of the IgG class, and were subtreshold for the VN reaction. The antibody titers determined by the PSH reaction were 7 to 10 times higher than these determined by the VN reaction, while their mean titer in serums with minimum VN index 1.0 was 1:23. The conclusion is drawn that PSH can be used as an independent serological test.", "contents": "[Serological diagnosis of IBR. Comparative studies of cattle sera in the virus neurtalization and passive hemagglutination reactions]. Three hundred eighty six cattle serums were simultaneously investigated by virus neutralizing (VN) and passive hemagglutination (PSH) reactions. Results obtained by the two methods coincided in 94% of the sermums studied and all serums with VN antibodies had also antibodies which can be established by the PSH reaction. About 6% of the positive reagents for PSH reaction were negative for the VN reaction. These were serums containing early antibodies (IgM) or low-titer antibodies of the IgG class, and were subtreshold for the VN reaction. The antibody titers determined by the PSH reaction were 7 to 10 times higher than these determined by the VN reaction, while their mean titer in serums with minimum VN index 1.0 was 1:23. The conclusion is drawn that PSH can be used as an independent serological test."}
{"id": "PMID:232332", "title": "[Experimental selection of weakly virulent strains of Aujeszky's disease virus].", "content": "An attempt was made to select slightly virulent strains by consecutive passages in cell cultures and use of extreme dilutions applying the temperature test (heating up to 50 degrees C for 1 hour). Initial and final fractions were compared for lethality and pruritus on rabbits and studied by the plate method. Levelling of the cytopathogenic titer after heating heated and unheated virus was achieved in laboratory samples isolated from lungs, and in two strains -- isolated from brains. This was achieved in the various strains following a varying number of passages, less in those isolated from lungs and more in those isolated from brains. Initial strains isolated from brains cause, while the lines produced by them do not cause, scratching in the infected rabbits. Temperature sensitive strains (identified by this test as virulent) produce mainly large (1.2 mm) plates, while the vaccine strain and the strains identified by the test as slightly virulent produce mainly small (0,8 mm) plates.", "contents": "[Experimental selection of weakly virulent strains of Aujeszky's disease virus]. An attempt was made to select slightly virulent strains by consecutive passages in cell cultures and use of extreme dilutions applying the temperature test (heating up to 50 degrees C for 1 hour). Initial and final fractions were compared for lethality and pruritus on rabbits and studied by the plate method. Levelling of the cytopathogenic titer after heating heated and unheated virus was achieved in laboratory samples isolated from lungs, and in two strains -- isolated from brains. This was achieved in the various strains following a varying number of passages, less in those isolated from lungs and more in those isolated from brains. Initial strains isolated from brains cause, while the lines produced by them do not cause, scratching in the infected rabbits. Temperature sensitive strains (identified by this test as virulent) produce mainly large (1.2 mm) plates, while the vaccine strain and the strains identified by the test as slightly virulent produce mainly small (0,8 mm) plates."}
{"id": "PMID:232333", "title": "[Isolation of the bovine herpesvirus-3 from sick calves].", "content": "Three herpes strains identified as herpes virus-3 were isolated in revolving test-tubes with cell cultures of nasal samples and lung parenchyma from diseased calves at the time of a respiratory enzooty. Large crystalloid aggregates of herpes virus virions were observed in the nucleus and in the cytoplasma by the electron-microscopic investigation performed on infected cell cultures. The experimental infection of calves with the isolated strain produced slight symptoms of respiratory disease in single calves only. The infected calves were susceptible to a following infection with cattle herpes virus-1.", "contents": "[Isolation of the bovine herpesvirus-3 from sick calves]. Three herpes strains identified as herpes virus-3 were isolated in revolving test-tubes with cell cultures of nasal samples and lung parenchyma from diseased calves at the time of a respiratory enzooty. Large crystalloid aggregates of herpes virus virions were observed in the nucleus and in the cytoplasma by the electron-microscopic investigation performed on infected cell cultures. The experimental infection of calves with the isolated strain produced slight symptoms of respiratory disease in single calves only. The infected calves were susceptible to a following infection with cattle herpes virus-1."}
{"id": "PMID:232334", "title": "[Serological diagnosis of IBR. Passive hemagglutination microreaction].", "content": "The preparation and standardization of the ingredients for PHA is described in detail. Formalin treated erythrocites in a 10% concentration treated with 1:20 000 tannin were used. The antigen concentrated by ultracentrifugation properly sensibilizes the erythrocites and their titer does not change in case of its dilution up to 1:8. The non-concentrated virus antigen has a low covering potential only if it is either not diluted, or in a 1:2 dilution and sensibilizes the erythrocites to a lesser extent. The great advantage of the use of concentrated antigen is that it equalizes antigens obtained from various lots. The optimal time for loading by erythrocites is 1 h, and a longer sensibilization has no influence on the effect of loading. It was proven that the sensibilization of formalin treated erythrocites allows long storage of the produced antigen. The tannin treated formalinized erythrocites can be stored up to 20 days without any change in their ability to be antigen covered, while the sensibilized erythrocites are not changed for 6 days and up to the 30th day their titer is twice lower, but this is of no practical importance.", "contents": "[Serological diagnosis of IBR. Passive hemagglutination microreaction]. The preparation and standardization of the ingredients for PHA is described in detail. Formalin treated erythrocites in a 10% concentration treated with 1:20 000 tannin were used. The antigen concentrated by ultracentrifugation properly sensibilizes the erythrocites and their titer does not change in case of its dilution up to 1:8. The non-concentrated virus antigen has a low covering potential only if it is either not diluted, or in a 1:2 dilution and sensibilizes the erythrocites to a lesser extent. The great advantage of the use of concentrated antigen is that it equalizes antigens obtained from various lots. The optimal time for loading by erythrocites is 1 h, and a longer sensibilization has no influence on the effect of loading. It was proven that the sensibilization of formalin treated erythrocites allows long storage of the produced antigen. The tannin treated formalinized erythrocites can be stored up to 20 days without any change in their ability to be antigen covered, while the sensibilized erythrocites are not changed for 6 days and up to the 30th day their titer is twice lower, but this is of no practical importance."}
{"id": "PMID:232338", "title": "N-mineralization of formaldehyde-releasing N-compounds.", "content": "The mineralization of several N-compounds, such as MMU, DMU, and HMT, as well as their respective nitrificide action, have been investigated. It has been proved that the amount of available formaldehyde, as well as its rate of release, are responsible for the specific action of these compounds on the N-mineralization process. Factors affecting the rate of release, namely molecular structure, solubility, and temperature, are discussed as well. Importance of these N-compounds as slow-release N-fertilizers based on a new molecular-microbiological approach is described.", "contents": "N-mineralization of formaldehyde-releasing N-compounds. The mineralization of several N-compounds, such as MMU, DMU, and HMT, as well as their respective nitrificide action, have been investigated. It has been proved that the amount of available formaldehyde, as well as its rate of release, are responsible for the specific action of these compounds on the N-mineralization process. Factors affecting the rate of release, namely molecular structure, solubility, and temperature, are discussed as well. Importance of these N-compounds as slow-release N-fertilizers based on a new molecular-microbiological approach is described."}
{"id": "PMID:232339", "title": "Enhancement of the antiviral activity of pyrimidine derivatives against mengovirus by visible light.", "content": "Eleven pyrimido-pyrimidine derivatives, seven with significant antiviral activity against Mengovirus, five against Coxsackie B1 virus and four antiviral negative compounds were tested for their photosensitizing ability. All seven compounds with antiviral activity in vitro showed an enhanced antiviral action against Mengovirus under irradiation with visible light, a fact that may be caused by photodynamic processes. It was tried to correlate the oxidation potentials of sensitizers with their photodynamic activity. By means of mass-spectrometric investigations, molecular fragmentation was examined following thin layer chromatography (TCL) before and after irradiation. Furthermore, binding affinity to biopolymers (BSA and RNA) was investigated to reveal conformity in differences of antiviral activity. The main results are the following: 1. Generally, strong antiviral activity can be correlated with strong binding affinity. 2. No significant correlation could be detected between oxidation potentials of antiviral compounds and their enhanced antiviral activity under irradiation conditions, although in some cases sensitizer with higher oxidation potentials are more effective than those with lower ones. 3. The lower the photostability of the compounds the higher was the light-induced antiviral activity. 4. No alteration of the molecular ion peak and fragmentation pattern before and after irradiation was indicated by means of mass-spectrometry and TLC using fairly comparable conditions.", "contents": "Enhancement of the antiviral activity of pyrimidine derivatives against mengovirus by visible light. Eleven pyrimido-pyrimidine derivatives, seven with significant antiviral activity against Mengovirus, five against Coxsackie B1 virus and four antiviral negative compounds were tested for their photosensitizing ability. All seven compounds with antiviral activity in vitro showed an enhanced antiviral action against Mengovirus under irradiation with visible light, a fact that may be caused by photodynamic processes. It was tried to correlate the oxidation potentials of sensitizers with their photodynamic activity. By means of mass-spectrometric investigations, molecular fragmentation was examined following thin layer chromatography (TCL) before and after irradiation. Furthermore, binding affinity to biopolymers (BSA and RNA) was investigated to reveal conformity in differences of antiviral activity. The main results are the following: 1. Generally, strong antiviral activity can be correlated with strong binding affinity. 2. No significant correlation could be detected between oxidation potentials of antiviral compounds and their enhanced antiviral activity under irradiation conditions, although in some cases sensitizer with higher oxidation potentials are more effective than those with lower ones. 3. The lower the photostability of the compounds the higher was the light-induced antiviral activity. 4. No alteration of the molecular ion peak and fragmentation pattern before and after irradiation was indicated by means of mass-spectrometry and TLC using fairly comparable conditions."}
{"id": "PMID:232340", "title": "[Nonspecific prophylaxis and therapy of Pseudomonas aeruginosa wound-infections with paramunization using a mouse-model (author's transl)].", "content": "The effectiveness of paramunization as a antigen nonspecific method to activate mechanisms against wound-infections due to Pseudomonas aeruginosa was studied using a model of direct infection of mice with a \"mice-pathogenic\" Ps. aeruginosa strain on artificially set wounds. Active paramunization by means of a biological inducer \"PIND-AVI\" (M-HP 438) significantly reduced the mortality rate between treated and placebo animals. The best results were obtained by parenteral prophylactic application. A four times repeated injection of PIND-AVI before the wound-infection reduced the mortality rate from 80% (placebo animals) to 26.6%. Almost equally good results were obtained by clinically useful therapeutic application of the preparation. A four times repeated treatment of the mice after wound infection lead to a decrease of mortality rates from 86.6% to 36.6%. The paramunization inducer PIND-AVI caused no side effect in any of the experiments. The mode of inducer action in Pseudomonas aeruginosa wound infections appears to be complex. Increased phagocytosis by nonspecific opsonisation, increased macrophage activity and concurrent stimulation of the lymphopoetic system could possible occur. On the other hand the nonspecific action of mediators could also play a role due to the inducer stimulated T-cells and cellular antigens of Pseudomonas aeruginosa. However both mechanisms in cooperation with specific and nonspecific humoral factors are probably interacting together. To what extent a simultaneous synthesis resp. release of endogeneous interferon plays a role is not known.", "contents": "[Nonspecific prophylaxis and therapy of Pseudomonas aeruginosa wound-infections with paramunization using a mouse-model (author's transl)]. The effectiveness of paramunization as a antigen nonspecific method to activate mechanisms against wound-infections due to Pseudomonas aeruginosa was studied using a model of direct infection of mice with a \"mice-pathogenic\" Ps. aeruginosa strain on artificially set wounds. Active paramunization by means of a biological inducer \"PIND-AVI\" (M-HP 438) significantly reduced the mortality rate between treated and placebo animals. The best results were obtained by parenteral prophylactic application. A four times repeated injection of PIND-AVI before the wound-infection reduced the mortality rate from 80% (placebo animals) to 26.6%. Almost equally good results were obtained by clinically useful therapeutic application of the preparation. A four times repeated treatment of the mice after wound infection lead to a decrease of mortality rates from 86.6% to 36.6%. The paramunization inducer PIND-AVI caused no side effect in any of the experiments. The mode of inducer action in Pseudomonas aeruginosa wound infections appears to be complex. Increased phagocytosis by nonspecific opsonisation, increased macrophage activity and concurrent stimulation of the lymphopoetic system could possible occur. On the other hand the nonspecific action of mediators could also play a role due to the inducer stimulated T-cells and cellular antigens of Pseudomonas aeruginosa. However both mechanisms in cooperation with specific and nonspecific humoral factors are probably interacting together. To what extent a simultaneous synthesis resp. release of endogeneous interferon plays a role is not known."}
{"id": "PMID:232341", "title": "The effect of nalidixic acid on microaerophilic and anaerobic bacteria. Special study of clostridia.", "content": "Study of the sensitivity of 141 strains of anaerobic and microaerophilic bacteria to nalidixic acid shows that few bacteria are inhibited by low concentrations (Veillonella, Eikenella, most of the Clostridia). Nalidixic acid appears to be bactericidal with respect to Clostridium perfringens, and its point of attack in the DNA is probably different from that of metronidazole.", "contents": "The effect of nalidixic acid on microaerophilic and anaerobic bacteria. Special study of clostridia. Study of the sensitivity of 141 strains of anaerobic and microaerophilic bacteria to nalidixic acid shows that few bacteria are inhibited by low concentrations (Veillonella, Eikenella, most of the Clostridia). Nalidixic acid appears to be bactericidal with respect to Clostridium perfringens, and its point of attack in the DNA is probably different from that of metronidazole."}
{"id": "PMID:232345", "title": "[Purification of horseradish peroxidase conjugated IGG by affinity chromatography. Comparison of glutaraldehyde and periodate conjugation].", "content": "By affinity chromatography of the coupling mixture on Concanavalin-A-Sepharose unlabeled IgG is completely removed. HRP conjugated IgG is then separated from free HRP by gelfiltration. Glutaraldehyde conjugation yielded 20 to 68% unlabeled IgG, depending on the duration of glutaraldehyde addition, and periodate conjugation yielded 10 to 28% unlabeled IgG. By this method fractions of conjugates with 3fold spec. act. were obtained by the glutaraldehydemethod and with 1.6fold spec. act. by periodate method as compared with gelfiltration. The periodate method guarantees a 3fold higher yield of HRP-labeled IgG compares with glutaraldehyde method. Both methods produce conjugates of the same spec. act. although the denaturation of HRP is much greater at periodate conjugation. When applying of affinity chromatography and gelfiltration. Crude HRP with 7% spec. act. of purified HRP resulted in conjugates having a spec. act. of 85% of those with purified HRP.", "contents": "[Purification of horseradish peroxidase conjugated IGG by affinity chromatography. Comparison of glutaraldehyde and periodate conjugation]. By affinity chromatography of the coupling mixture on Concanavalin-A-Sepharose unlabeled IgG is completely removed. HRP conjugated IgG is then separated from free HRP by gelfiltration. Glutaraldehyde conjugation yielded 20 to 68% unlabeled IgG, depending on the duration of glutaraldehyde addition, and periodate conjugation yielded 10 to 28% unlabeled IgG. By this method fractions of conjugates with 3fold spec. act. were obtained by the glutaraldehydemethod and with 1.6fold spec. act. by periodate method as compared with gelfiltration. The periodate method guarantees a 3fold higher yield of HRP-labeled IgG compares with glutaraldehyde method. Both methods produce conjugates of the same spec. act. although the denaturation of HRP is much greater at periodate conjugation. When applying of affinity chromatography and gelfiltration. Crude HRP with 7% spec. act. of purified HRP resulted in conjugates having a spec. act. of 85% of those with purified HRP."}
{"id": "PMID:232346", "title": "Lack of sequence homology between the nucleic acids of Rauscher leukaemia virus and polyoma virus Y8e produced simultaneously in a continuous mouse cell line.", "content": "In a continuous cell line (Y8e) from spleen and thymus cells of mice, infected with RLV, the presence of both RLV and polyoma virus Y8e in a single cell could be demonstrated by electron microscopy. A comparison of the nucleic acids of RLV and polyoma virus from Y8e cells by two molecular hybridization methods showed lack of sequence homology between the viral nucleic acids.", "contents": "Lack of sequence homology between the nucleic acids of Rauscher leukaemia virus and polyoma virus Y8e produced simultaneously in a continuous mouse cell line. In a continuous cell line (Y8e) from spleen and thymus cells of mice, infected with RLV, the presence of both RLV and polyoma virus Y8e in a single cell could be demonstrated by electron microscopy. A comparison of the nucleic acids of RLV and polyoma virus from Y8e cells by two molecular hybridization methods showed lack of sequence homology between the viral nucleic acids."}
{"id": "PMID:232347", "title": "Ontogenetic development of 3,5-adenosine monophosphate phosphodiesterase in guinea pig and rat ileum.", "content": "The postnatal development of phosphodiesterases with low and high Michaelis constants in guinea pig and rat ileum was studied. The tow types of phosphodiesterases were found to increase their activity post partum, and this increase was particulary pronounced in the rat. The rise in the enzyme activity took place mainly at the expense of the increase of the phosphodiesterase with high Km. In addition to the quantitative differences in the phosphodiesterase activity of yound and adult animals, considerable age differences were also observed in the sensitivity of the enzyme to inhibitors and activators. These data can contribute to the explanation of the differences in the action of some drugs influencing the phosphodiesterase in young and adult organisms.", "contents": "Ontogenetic development of 3,5-adenosine monophosphate phosphodiesterase in guinea pig and rat ileum. The postnatal development of phosphodiesterases with low and high Michaelis constants in guinea pig and rat ileum was studied. The tow types of phosphodiesterases were found to increase their activity post partum, and this increase was particulary pronounced in the rat. The rise in the enzyme activity took place mainly at the expense of the increase of the phosphodiesterase with high Km. In addition to the quantitative differences in the phosphodiesterase activity of yound and adult animals, considerable age differences were also observed in the sensitivity of the enzyme to inhibitors and activators. These data can contribute to the explanation of the differences in the action of some drugs influencing the phosphodiesterase in young and adult organisms."}
{"id": "PMID:232353", "title": "Combined test of hypothalamic-pituitary function in growth-retarded children treated with growth hormone. II. Secretion of LH, FSH, TSH, prolactin and ACTH.", "content": "A total number of 23 patients treated with human growth hormone were retested by use of a combined pituitary stimulation test. Plasma concentrations of GH, FSH, LH, TSH, T4, T3, prolactin (PRL), ACTH and cortisol were measured before and after stimulation with hypoglycemia, TRH and LHRH. The test was performed in patients with persistent GH deficiency (group A) and patients with transitory GH deficiency (group B). In group A a normal pubertal development was found in three patients, whereas in prepubertal subjects the FSH/LH responses were smaller than those of prepubertal patients in group B. Also plasma ACTH increase was less pronounced in group A patients than in group B. In contrast, the plasma TSH and PRL responses were more sustained in group A than in group B. The secretory pattern of TSH and PRL was comparable in the two groups of patients. Thus, in patients with persistent GH deficiency additional multiple disturbances of the hypothalamic-pituitary function often appeared whereas in most patients with transitory GH deficiency the combined pituitary test was normal at the reinvestigation.", "contents": "Combined test of hypothalamic-pituitary function in growth-retarded children treated with growth hormone. II. Secretion of LH, FSH, TSH, prolactin and ACTH. A total number of 23 patients treated with human growth hormone were retested by use of a combined pituitary stimulation test. Plasma concentrations of GH, FSH, LH, TSH, T4, T3, prolactin (PRL), ACTH and cortisol were measured before and after stimulation with hypoglycemia, TRH and LHRH. The test was performed in patients with persistent GH deficiency (group A) and patients with transitory GH deficiency (group B). In group A a normal pubertal development was found in three patients, whereas in prepubertal subjects the FSH/LH responses were smaller than those of prepubertal patients in group B. Also plasma ACTH increase was less pronounced in group A patients than in group B. In contrast, the plasma TSH and PRL responses were more sustained in group A than in group B. The secretory pattern of TSH and PRL was comparable in the two groups of patients. Thus, in patients with persistent GH deficiency additional multiple disturbances of the hypothalamic-pituitary function often appeared whereas in most patients with transitory GH deficiency the combined pituitary test was normal at the reinvestigation."}
{"id": "PMID:232354", "title": "Low urinary estriol during pregnancy caused by isolated fetal ACTH-deficiency.", "content": "In a 34-year-old pregnant woman, serum HPL and urinary HCG were normal, but urinary estriol was repeatedly low. A normal boy was delivered after 38 week gestation. During the neonatal period, he had hypoglycemia, muscular hypotonia and transient hyperbilirubinemia. The ACTH-test was normal, but the THS-response to metyrapone was low. Serum ACTH did not respond to insulin and metyrapone. Growth hormone, TSH and gonadotropin responses to stimuli were normal. Treatment with hydrocortisone resulted in disappearance of the symptoms. It is concluded that fetal ACTH-deficiency is one of the specific endocrine causes of low maternal estriol.", "contents": "Low urinary estriol during pregnancy caused by isolated fetal ACTH-deficiency. In a 34-year-old pregnant woman, serum HPL and urinary HCG were normal, but urinary estriol was repeatedly low. A normal boy was delivered after 38 week gestation. During the neonatal period, he had hypoglycemia, muscular hypotonia and transient hyperbilirubinemia. The ACTH-test was normal, but the THS-response to metyrapone was low. Serum ACTH did not respond to insulin and metyrapone. Growth hormone, TSH and gonadotropin responses to stimuli were normal. Treatment with hydrocortisone resulted in disappearance of the symptoms. It is concluded that fetal ACTH-deficiency is one of the specific endocrine causes of low maternal estriol."}
{"id": "PMID:232355", "title": "Growth in Turner's syndrome: spontaneous and fluoxymesterone stimulated.", "content": "Spontaneous growth was analysed in a group of 55 girls with Turner's syndrome and various karyotypes. Their variation in height and its dependence on parental height were similar to that of normal girls. At all ages, the 45,X karyotype was associated with slightly greater mean stature than the other karyotypes together. The bone ages lagged progressively behind from 10 years onwards. Twenty-five patients aged between 9.1 and 17.2 years were given fluoxymesterone, 0.06-0.17 mg/kg daily, for at least 1 year. Their height velocities increased significantly. This brought about a clear psychological benefit. Their final heights were predicted before and after therapy, with a new method based on the spontaneous growth and bone maturation of our patients. The response was individually variable but, on average, the patients gained in predicted height from the therapy. This effect was not lost during a posttreatment year. Abnormal lowering of the voice occurred in patients receiving greater than or equal to 0.15 mg/kg fluoxymesterone daily, but never with less than 0.13 mg/kg. No other adverse effects appeared. Thus, fluoxymesterone is useful for promoting growth in girls with Turner's syndrome.", "contents": "Growth in Turner's syndrome: spontaneous and fluoxymesterone stimulated. Spontaneous growth was analysed in a group of 55 girls with Turner's syndrome and various karyotypes. Their variation in height and its dependence on parental height were similar to that of normal girls. At all ages, the 45,X karyotype was associated with slightly greater mean stature than the other karyotypes together. The bone ages lagged progressively behind from 10 years onwards. Twenty-five patients aged between 9.1 and 17.2 years were given fluoxymesterone, 0.06-0.17 mg/kg daily, for at least 1 year. Their height velocities increased significantly. This brought about a clear psychological benefit. Their final heights were predicted before and after therapy, with a new method based on the spontaneous growth and bone maturation of our patients. The response was individually variable but, on average, the patients gained in predicted height from the therapy. This effect was not lost during a posttreatment year. Abnormal lowering of the voice occurred in patients receiving greater than or equal to 0.15 mg/kg fluoxymesterone daily, but never with less than 0.13 mg/kg. No other adverse effects appeared. Thus, fluoxymesterone is useful for promoting growth in girls with Turner's syndrome."}
{"id": "PMID:232356", "title": "Acute response of parathyroid hormone in congenital osteopetrosis.", "content": "Indices of calcium and phosphorus metabolism were studied in 3 children with osteopetrosis before and after infusion of bovine parathyroid hormone extract. Basal plasma concentrations of calcium, alkaline phosphatase and 25-hydroxy vitamin D tended to be low. Plasma immunoreactive PTH levels were at the upper normal range in two patients. A marked increase in urinary cyclic AMP in all patients was solely due to an increase in the nephrogenous cAMP. After vitamin D treatment urinary cAMP was essentially unchanged with the same preponderance of nephrogenous cAMP. Following PTH infusion plasma cAMP showed a brisk rise. There was also a prompt rise in urinary cAMP and a distinct decrease in the calcium to sodium clearance ratio indicating increased calcium reabsorption. Phosphaturic effect was only observed when PTH was given in the highest dose level. The findings are consistent with a state of low grade hyperparathyroidism which could not be related to the plasma levels of 25-hydroxy vitamin D or calcium.", "contents": "Acute response of parathyroid hormone in congenital osteopetrosis. Indices of calcium and phosphorus metabolism were studied in 3 children with osteopetrosis before and after infusion of bovine parathyroid hormone extract. Basal plasma concentrations of calcium, alkaline phosphatase and 25-hydroxy vitamin D tended to be low. Plasma immunoreactive PTH levels were at the upper normal range in two patients. A marked increase in urinary cyclic AMP in all patients was solely due to an increase in the nephrogenous cAMP. After vitamin D treatment urinary cAMP was essentially unchanged with the same preponderance of nephrogenous cAMP. Following PTH infusion plasma cAMP showed a brisk rise. There was also a prompt rise in urinary cAMP and a distinct decrease in the calcium to sodium clearance ratio indicating increased calcium reabsorption. Phosphaturic effect was only observed when PTH was given in the highest dose level. The findings are consistent with a state of low grade hyperparathyroidism which could not be related to the plasma levels of 25-hydroxy vitamin D or calcium."}
{"id": "PMID:232357", "title": "The effect of sympathicomimetic agents on carbohydrate metabolism of planaria.", "content": "Epinephrine, ephedrine, dopamine and isoproterenol considerably influence carbohydrate utilization in planaria. Dopamine alone and in combination is the most potent, while ephedrine the least effective in this respect. The finding of increased responses to combined treatment supports the view of the existence of different receptor sites for the sympathicomimetic drugs. The results substantiate conclusions concerning the phylogenesis of hormone receptors.", "contents": "The effect of sympathicomimetic agents on carbohydrate metabolism of planaria. Epinephrine, ephedrine, dopamine and isoproterenol considerably influence carbohydrate utilization in planaria. Dopamine alone and in combination is the most potent, while ephedrine the least effective in this respect. The finding of increased responses to combined treatment supports the view of the existence of different receptor sites for the sympathicomimetic drugs. The results substantiate conclusions concerning the phylogenesis of hormone receptors."}
{"id": "PMID:232358", "title": "Sensitivity of European microtines to injected CdCl2.", "content": "Basic histologic and metabolic indices of damage to the testes by CdCl2 were observed in six species of rodents: Lagurus lagurus, Pitymys subterraneus, Microtus oeconomus, M. agrestis, Clethrionomys glareolus (and Mus musculus for comparison). All species showed discoloration of the subcapsular tissues and damage to the testicular parenchyma. Testes of all species receiving CdCl2 utilized from 43% to 76% less oxygen than did those from untreated individuals. Cadmium treatment preceded few significant temperature shifts. The voles observed experienced differential sensitivity to CdCl2 and should be quite suitable for further studies of the mechanism of action of CdCl2 as a testicular poison.", "contents": "Sensitivity of European microtines to injected CdCl2. Basic histologic and metabolic indices of damage to the testes by CdCl2 were observed in six species of rodents: Lagurus lagurus, Pitymys subterraneus, Microtus oeconomus, M. agrestis, Clethrionomys glareolus (and Mus musculus for comparison). All species showed discoloration of the subcapsular tissues and damage to the testicular parenchyma. Testes of all species receiving CdCl2 utilized from 43% to 76% less oxygen than did those from untreated individuals. Cadmium treatment preceded few significant temperature shifts. The voles observed experienced differential sensitivity to CdCl2 and should be quite suitable for further studies of the mechanism of action of CdCl2 as a testicular poison."}
{"id": "PMID:232359", "title": "Inhibition of the stimulatory effect of ACTH on adrenal and ovarian blood flow by indomethacin in the dog.", "content": "In anoestrous dogs heated thermocouples were inserted into one of the adrenals and ovaries. The basal adrenal and ovarian blood flow was recorded and enhanced by 1.2, 2.5 or 5.0 micrograms/kg of intravenous ACTH before and after the intravenous administration of 20 or 50 mg/kg of indomethacin. Indomethacin, depending on the dose and on the time elapsing after its administration inhibited the enhancing effect of ACTH on adrenal and ovarian blood flow. Since indomethacin is a specific inhibitor of prostaglandin synthesis it has been suggested that prostaglandins act as mediators in the vasodilatation elicited by ACTH in the canine adrenal and ovary.", "contents": "Inhibition of the stimulatory effect of ACTH on adrenal and ovarian blood flow by indomethacin in the dog. In anoestrous dogs heated thermocouples were inserted into one of the adrenals and ovaries. The basal adrenal and ovarian blood flow was recorded and enhanced by 1.2, 2.5 or 5.0 micrograms/kg of intravenous ACTH before and after the intravenous administration of 20 or 50 mg/kg of indomethacin. Indomethacin, depending on the dose and on the time elapsing after its administration inhibited the enhancing effect of ACTH on adrenal and ovarian blood flow. Since indomethacin is a specific inhibitor of prostaglandin synthesis it has been suggested that prostaglandins act as mediators in the vasodilatation elicited by ACTH in the canine adrenal and ovary."}
{"id": "PMID:232360", "title": "Involvement of dopaminergic receptors in action of corticotropin releasing factor (CRF) under in vitro conditions.", "content": "ACTH release under the effect of median eminence extract (ME) was studied in both incubation and superfusion experiments. ACTH content of the incubation medium was measured by radioimmunoassay or by the corticosterone production of trypsinisolated adrenocortical cells. Dopamine at low concentration led to a slight increase of basal ACTH secretion, while at higher concentration failed to influence ACTH release. The dopamine agonist CB-154 produced a significant rise of ACTH secretion and augmented the ME extract-induced increase of pituitary ACTH release. Chlorpromazine and haloperidol suppressed basal ACTH secretion and inhibited the ME extract-induced release. The simultaneous administration of CB-154 and haloperidol into the incubation medium prevented the haloperidol-induced inhibition of ACTH release. The observations indicate that dopaminergic receptors play a role in the activation of CRF-induced ACTH secretion under in vitro experimental conditions.", "contents": "Involvement of dopaminergic receptors in action of corticotropin releasing factor (CRF) under in vitro conditions. ACTH release under the effect of median eminence extract (ME) was studied in both incubation and superfusion experiments. ACTH content of the incubation medium was measured by radioimmunoassay or by the corticosterone production of trypsinisolated adrenocortical cells. Dopamine at low concentration led to a slight increase of basal ACTH secretion, while at higher concentration failed to influence ACTH release. The dopamine agonist CB-154 produced a significant rise of ACTH secretion and augmented the ME extract-induced increase of pituitary ACTH release. Chlorpromazine and haloperidol suppressed basal ACTH secretion and inhibited the ME extract-induced release. The simultaneous administration of CB-154 and haloperidol into the incubation medium prevented the haloperidol-induced inhibition of ACTH release. The observations indicate that dopaminergic receptors play a role in the activation of CRF-induced ACTH secretion under in vitro experimental conditions."}
{"id": "PMID:232361", "title": "Circadian peculiarities of daytime sleep in 1 to 6 months old infants (electrophysiological study).", "content": "A longitudinal study of 6 normal, full-term infants was carried out. Polygrams of three subsequent daytime sleep periods (morning, noon, afternoon) were recorded at monthly intervals. It was established that: (a) Over the first 3 postnatal months the noon period was the longest (98.96 min), and each sleep period consisted most frequently of 2 cycles. Over the second 3 months the afternoon period shortened significantly from 68.69 min to 41.92 min and consisted exclusively of 1 cycle. (b) The delta sleep percentage was the greatest (52%) over the first 3 months in the morning period and over the second 3 months it was almost equal in all the three periods. The paradoxical sleep percentage over the first 3 postnatal months was equal in all the three periods, but over the second 3 months it became smaller in the afternoon period, (c) The heart rate values were lowest in the morning period, this phenomenon being clearly expressed during the delta sleep. One minute time (in sec), occupied by REMs, was evaluated and it was found that this parameter was not influenced by age and timing of sleep periods, but there existed positive correlation between this time and the duration of the paradoxical phase under estimation.", "contents": "Circadian peculiarities of daytime sleep in 1 to 6 months old infants (electrophysiological study). A longitudinal study of 6 normal, full-term infants was carried out. Polygrams of three subsequent daytime sleep periods (morning, noon, afternoon) were recorded at monthly intervals. It was established that: (a) Over the first 3 postnatal months the noon period was the longest (98.96 min), and each sleep period consisted most frequently of 2 cycles. Over the second 3 months the afternoon period shortened significantly from 68.69 min to 41.92 min and consisted exclusively of 1 cycle. (b) The delta sleep percentage was the greatest (52%) over the first 3 months in the morning period and over the second 3 months it was almost equal in all the three periods. The paradoxical sleep percentage over the first 3 postnatal months was equal in all the three periods, but over the second 3 months it became smaller in the afternoon period, (c) The heart rate values were lowest in the morning period, this phenomenon being clearly expressed during the delta sleep. One minute time (in sec), occupied by REMs, was evaluated and it was found that this parameter was not influenced by age and timing of sleep periods, but there existed positive correlation between this time and the duration of the paradoxical phase under estimation."}
{"id": "PMID:232364", "title": "Inhibitory actions from low and high threshold cutaneous afferents on groups II and III muscle afferent pathways in the spinal cat.", "content": "The inhibitory effects caused by volleys in cutaneous afferents on the transmission through some polysynaptic segmental pathways activated by high threshold muscle afferents were studied in chloralose anesthetized, spinal cats. Pathways studied were groups II and III to motoneurones as well as group II to primary afferents. The results suggested that two different mechanisms were involved. One mechanism, with a very slow time course (duration more than 400 ms), is suggested to be an example of presynaptic inhibition between different primary afferent systems. This mechanism required high threshold (greater than or equal to 1.6T) conditioning shocks, and appeared simultaneously with the component II dorsal root potential being evoked by the cutaneous afferent volley. The other mechanism, with a faster time course (duration always below 300 ms), was dependent upon low threshold (less than or equal to 1.5T) cutaneous conditioning volleys. This inhibitory interaction could not be ascribed to the same presynaptic mechanism, but is suggested to be an example of postsynaptic inhibition at an interneuronal level. The presumed disynaptic excitatory pathway from group II muscle afferents to flexor motoneurones was not inhibited by cutaneous conditioning shocks, but could on the contrary be facilitated by activity in low threshold cutaneous afferents, probably at the only interneurone involved in this group II pathway.", "contents": "Inhibitory actions from low and high threshold cutaneous afferents on groups II and III muscle afferent pathways in the spinal cat. The inhibitory effects caused by volleys in cutaneous afferents on the transmission through some polysynaptic segmental pathways activated by high threshold muscle afferents were studied in chloralose anesthetized, spinal cats. Pathways studied were groups II and III to motoneurones as well as group II to primary afferents. The results suggested that two different mechanisms were involved. One mechanism, with a very slow time course (duration more than 400 ms), is suggested to be an example of presynaptic inhibition between different primary afferent systems. This mechanism required high threshold (greater than or equal to 1.6T) conditioning shocks, and appeared simultaneously with the component II dorsal root potential being evoked by the cutaneous afferent volley. The other mechanism, with a faster time course (duration always below 300 ms), was dependent upon low threshold (less than or equal to 1.5T) cutaneous conditioning volleys. This inhibitory interaction could not be ascribed to the same presynaptic mechanism, but is suggested to be an example of postsynaptic inhibition at an interneuronal level. The presumed disynaptic excitatory pathway from group II muscle afferents to flexor motoneurones was not inhibited by cutaneous conditioning shocks, but could on the contrary be facilitated by activity in low threshold cutaneous afferents, probably at the only interneurone involved in this group II pathway."}
{"id": "PMID:232365", "title": "Adenosine 3',5' cyclic monophosphate, calcium and magnesium excretion in ethanol intoxication and hangover.", "content": "Effect of ethanol on adenosine 3', 5' cyclic monophosphate (cAMP), calcium (Ca) and magnesium (Mg) excretion was studied in controlled clinical conditions in man. Seven male volunteers served as their own controls. In 5 subjects cAMP excretion was primarily suppressed by ethanol. Ethanol appeared to have a biphasic effect on Ca excretion, an initial stimulation followed by a conservation phase. Mg excretion was stimulated by ethanol in 5 subjects. Subjects having nausea and vomitus and the most severe hangover symptoms had the lowest urinary Ca excretion and the lowest imitial cAMP excretion. Ca and Mg metabolism and the susceptibility of the body to the toxic effects of ethanol appeared to be interrelated.", "contents": "Adenosine 3',5' cyclic monophosphate, calcium and magnesium excretion in ethanol intoxication and hangover. Effect of ethanol on adenosine 3', 5' cyclic monophosphate (cAMP), calcium (Ca) and magnesium (Mg) excretion was studied in controlled clinical conditions in man. Seven male volunteers served as their own controls. In 5 subjects cAMP excretion was primarily suppressed by ethanol. Ethanol appeared to have a biphasic effect on Ca excretion, an initial stimulation followed by a conservation phase. Mg excretion was stimulated by ethanol in 5 subjects. Subjects having nausea and vomitus and the most severe hangover symptoms had the lowest urinary Ca excretion and the lowest imitial cAMP excretion. Ca and Mg metabolism and the susceptibility of the body to the toxic effects of ethanol appeared to be interrelated."}
{"id": "PMID:232366", "title": "Modification of human pain threshold by specific tactile receptors.", "content": "The effects of conditioning vibrotactile stimulation of particular tactile receptor groups on thresholds to painful electric stimuli were studied in seven healthy adults. Preferentially Pacinian afferents were activated with conditioning sinusoidal vibration of 240 Hz at 20 and 200 micrometers amplitudes and preferentially non-Pacinian tactile fibers were activated with conditioning sinusoidal vibration of 20 Hz at 200 and 400 micrometers amplitudes. None of the subjects showed pain threshold elevation during activation of non-Pacinian tactile fibers. However, 6 of the 7 subjects showed significant pain threshold elevation with conditioning vibration stimulus of 240 Hz at 200 micrometers amplitude, and 4 subjects showed significantly elevated pain thresholds with conditioning stimulus of 240 Hz at 20 micrometers amplitude. It is concluded that the activation of Pacinian afferents causes inhibition of pain conducting pathways.", "contents": "Modification of human pain threshold by specific tactile receptors. The effects of conditioning vibrotactile stimulation of particular tactile receptor groups on thresholds to painful electric stimuli were studied in seven healthy adults. Preferentially Pacinian afferents were activated with conditioning sinusoidal vibration of 240 Hz at 20 and 200 micrometers amplitudes and preferentially non-Pacinian tactile fibers were activated with conditioning sinusoidal vibration of 20 Hz at 200 and 400 micrometers amplitudes. None of the subjects showed pain threshold elevation during activation of non-Pacinian tactile fibers. However, 6 of the 7 subjects showed significant pain threshold elevation with conditioning vibration stimulus of 240 Hz at 200 micrometers amplitude, and 4 subjects showed significantly elevated pain thresholds with conditioning stimulus of 240 Hz at 20 micrometers amplitude. It is concluded that the activation of Pacinian afferents causes inhibition of pain conducting pathways."}
{"id": "PMID:232367", "title": "Efflux of cyclic AMP, prostaglandin E2 and F2 alpha and thromboxane B2 in leg lymph of rabbits after scalding injury.", "content": "Leg lymph was collected from pentobarbital anaesthetized rabbits before and after scalding injury of the paw (75 degrees C for 20 s), and the contents of cyclic AMP (cAMP), prostaglandin E2 (PGE2) and PGF2 alpha and thromboxane B2 (TXB2) in lymph were determined. After injury lymph flow increased about four times. The maximal rate of flow was found between 30 and 60 min after scalding. The efflux of cAMP and immunoreactive iPGE2, iPGF2 alpha and iTXB2 also increased. The maximum values were detected at approximately 0-30, 30-60, 30-60 and 180-240 min, respectively, after the injury. The output of cAMP, iPGE2 and iPGF2 alpha and iTXB2 in lymph of the contralateral non-scalded paw remained low throughout the experiments. When rabbits were injected with indomethacin (2.5 mg/kg) or diclofenac sodium (2.5 mg/kg) immediately after the scalding injury, the efflux of cAMP, iPGE2 and iPGF2 alpha were low. Lymph flow was markedly reduced after treatment with diclofenac sodium; treatment with indomethacin did not significantly affect lymph flow. The results suggest a prostaglandin-dependent formation of cAMP following scalding injury which may be related to the initial responses to scalding.", "contents": "Efflux of cyclic AMP, prostaglandin E2 and F2 alpha and thromboxane B2 in leg lymph of rabbits after scalding injury. Leg lymph was collected from pentobarbital anaesthetized rabbits before and after scalding injury of the paw (75 degrees C for 20 s), and the contents of cyclic AMP (cAMP), prostaglandin E2 (PGE2) and PGF2 alpha and thromboxane B2 (TXB2) in lymph were determined. After injury lymph flow increased about four times. The maximal rate of flow was found between 30 and 60 min after scalding. The efflux of cAMP and immunoreactive iPGE2, iPGF2 alpha and iTXB2 also increased. The maximum values were detected at approximately 0-30, 30-60, 30-60 and 180-240 min, respectively, after the injury. The output of cAMP, iPGE2 and iPGF2 alpha and iTXB2 in lymph of the contralateral non-scalded paw remained low throughout the experiments. When rabbits were injected with indomethacin (2.5 mg/kg) or diclofenac sodium (2.5 mg/kg) immediately after the scalding injury, the efflux of cAMP, iPGE2 and iPGF2 alpha were low. Lymph flow was markedly reduced after treatment with diclofenac sodium; treatment with indomethacin did not significantly affect lymph flow. The results suggest a prostaglandin-dependent formation of cAMP following scalding injury which may be related to the initial responses to scalding."}
{"id": "PMID:232368", "title": "Haemagglutination-inhibiting antibodies to B.K. virus in Hungary.", "content": "Antibody inhibiting the haemagglutination by B.K. virus was found in 64% of the serum samples collected from 949 subjects in Hungary. The frequency of seropositivity was the lowest (17%) among infants 1 and 2 years of age and the highest (93%) in the age group 16 to 20 years. The subsequent age groups showed a slow continuous decline. The age-distribution curve drawn on the basis of the geometric means of titres has two peaks, one between 3 and 5 years of age and another between 21 and 30 years of age, reaching 6.74 and 7.05, respectively, as expressed in terms of log2 units. The prevalence of haemagglutination-inhibiting antibody to B.K. virus in Hungary and its distribution by age are similar to those reported from other European countries.", "contents": "Haemagglutination-inhibiting antibodies to B.K. virus in Hungary. Antibody inhibiting the haemagglutination by B.K. virus was found in 64% of the serum samples collected from 949 subjects in Hungary. The frequency of seropositivity was the lowest (17%) among infants 1 and 2 years of age and the highest (93%) in the age group 16 to 20 years. The subsequent age groups showed a slow continuous decline. The age-distribution curve drawn on the basis of the geometric means of titres has two peaks, one between 3 and 5 years of age and another between 21 and 30 years of age, reaching 6.74 and 7.05, respectively, as expressed in terms of log2 units. The prevalence of haemagglutination-inhibiting antibody to B.K. virus in Hungary and its distribution by age are similar to those reported from other European countries."}
{"id": "PMID:232369", "title": "Isolation of cytopathogenic Rotavirus from neonatal calves.", "content": "Rotavirus was isolated in rolled calf kidney cultures from the intestinal contents of a calf suffering from diarrhoea. The cytopathic effect was demonstrated in native cultures as well as in stained preparations. The affected cells were elongated, became sickle-like in shape, disintegrated and detached from the monolayer. Virus-specific direct immunofluorescence ran parallel, in both time and intensity, with the cytopathic effects. Immuno-electron microscopy showed aggregated virus particles corresponding in size, shape and structure to Rotavirus virion.", "contents": "Isolation of cytopathogenic Rotavirus from neonatal calves. Rotavirus was isolated in rolled calf kidney cultures from the intestinal contents of a calf suffering from diarrhoea. The cytopathic effect was demonstrated in native cultures as well as in stained preparations. The affected cells were elongated, became sickle-like in shape, disintegrated and detached from the monolayer. Virus-specific direct immunofluorescence ran parallel, in both time and intensity, with the cytopathic effects. Immuno-electron microscopy showed aggregated virus particles corresponding in size, shape and structure to Rotavirus virion."}
{"id": "PMID:232372", "title": "Effect of acupuncture on adrenocortical hormone production: I. Variation in the ability for adrenocortical hormone production in relation to the duration of acupuncture stimulation.", "content": "The effect of acupuncture on adrenocortical hormone production in adult female albino rabbits of New Zealand strain was investigated. There was significant increase compared to the control cortisol and corticosterone following application of acupuncture at the locus Tsu-San-Li. In the non-locus group, such treatment resulted in only a transient raise followed by a significant fall in cortisol and corticosterone. Acupuncture treatment with electric current for 1 hour proved to be unique in that it gave rise to no biphasic change in the 14C uptake of the steroids. These results indicate that adrenal production of corticosterone and cortisol was enhanced by acupuncture and electroacupuncture at the Tsu-San-Li locus.", "contents": "Effect of acupuncture on adrenocortical hormone production: I. Variation in the ability for adrenocortical hormone production in relation to the duration of acupuncture stimulation. The effect of acupuncture on adrenocortical hormone production in adult female albino rabbits of New Zealand strain was investigated. There was significant increase compared to the control cortisol and corticosterone following application of acupuncture at the locus Tsu-San-Li. In the non-locus group, such treatment resulted in only a transient raise followed by a significant fall in cortisol and corticosterone. Acupuncture treatment with electric current for 1 hour proved to be unique in that it gave rise to no biphasic change in the 14C uptake of the steroids. These results indicate that adrenal production of corticosterone and cortisol was enhanced by acupuncture and electroacupuncture at the Tsu-San-Li locus."}
{"id": "PMID:232373", "title": "Focal nodular hyperplasia and adenoma of the liver. A pediatric experience.", "content": "Focal nodular hyperplasia and adenoma of the liver together represent approximately 2% of all primary hepatic tumors and tumor-like lesions in childhood. This study reports the clinical and pathologic features of focal nodular hyperplasia in three children, all females between 27 months and 15 years of age with asymptomatic hepatomegaly. In contrast, massive hemoperitoneum from a ruptured, hemorrhagic mass was the presentation of the hepatic adenoma in a 14-year-old girl. There was no history of administration of steroids in these four children. Angiography in two cases (one case each of focal nodular hyperplasia and hepatic adenoma) revealed hypervascular lesions with abnormal tortuous vessels suggesting a malignant tumor. Pathologically, the adenoma and focal nodular hyperplasia were readily distinguishable and the necessity for this differentiation was reviewed. All four patients are currently doing well.", "contents": "Focal nodular hyperplasia and adenoma of the liver. A pediatric experience. Focal nodular hyperplasia and adenoma of the liver together represent approximately 2% of all primary hepatic tumors and tumor-like lesions in childhood. This study reports the clinical and pathologic features of focal nodular hyperplasia in three children, all females between 27 months and 15 years of age with asymptomatic hepatomegaly. In contrast, massive hemoperitoneum from a ruptured, hemorrhagic mass was the presentation of the hepatic adenoma in a 14-year-old girl. There was no history of administration of steroids in these four children. Angiography in two cases (one case each of focal nodular hyperplasia and hepatic adenoma) revealed hypervascular lesions with abnormal tortuous vessels suggesting a malignant tumor. Pathologically, the adenoma and focal nodular hyperplasia were readily distinguishable and the necessity for this differentiation was reviewed. All four patients are currently doing well."}
{"id": "PMID:232374", "title": "Cystic nephroma (so-called polycystic Wilms' tumor) of childhood: a CT-pathologic study.", "content": "The unique CT features, heretofore unreported, of a case of cystic nephroma of childhood are presented. The concept that cystic nephroma is part of thc diagnosis of cystic nephroma can be made utilizing excretory urography and computerized tomography.", "contents": "Cystic nephroma (so-called polycystic Wilms' tumor) of childhood: a CT-pathologic study. The unique CT features, heretofore unreported, of a case of cystic nephroma of childhood are presented. The concept that cystic nephroma is part of thc diagnosis of cystic nephroma can be made utilizing excretory urography and computerized tomography."}
{"id": "PMID:232376", "title": "Histochemical analysis of Langerhans' cells.", "content": "Single cell suspensions of epidermal cells from guinea pigs were analyzed histochemically for the presence of the following enzymes: 5'-adenosine triphosphatase, nonspecific esterase, specific esterase, myeloperoxidase and leukocyte alkaline phosphatase. A population of cells was positive for nonspecific esterase, leukocyte alkaline phosphatase, and 5'-adenosine triphosphatase. This population was identified as Langerhans' cells because the number of cells stained for these enzymes paralleled the number of Langerhans' cells in the suspension. These same enzymes were shown to be present in guinea pig leukocytes of the mononuclear-phagocytic series, suggesting that they and Langerhans' cells may have a precursor in common.", "contents": "Histochemical analysis of Langerhans' cells. Single cell suspensions of epidermal cells from guinea pigs were analyzed histochemically for the presence of the following enzymes: 5'-adenosine triphosphatase, nonspecific esterase, specific esterase, myeloperoxidase and leukocyte alkaline phosphatase. A population of cells was positive for nonspecific esterase, leukocyte alkaline phosphatase, and 5'-adenosine triphosphatase. This population was identified as Langerhans' cells because the number of cells stained for these enzymes paralleled the number of Langerhans' cells in the suspension. These same enzymes were shown to be present in guinea pig leukocytes of the mononuclear-phagocytic series, suggesting that they and Langerhans' cells may have a precursor in common."}
{"id": "PMID:232377", "title": "Association of islet cell carcinoma of the pancreas with subcutaneous fat necrosis.", "content": "A 57-year-old man with generalized, subcutaneous fat necrosis was found at autopsy to have islet cell carcinoma of the pancreas. The histologic diagnosis of islet cell carcinoma was confirmed by the finding by electron microscopy of characteristic intracytoplasmic granules within pancreatic neoplastic cells. Lipase levels were elevated in serum as well as in tissues in areas of subcutaneous fat necrosis. Enzyme histochemical stains for alkaline and acid phosphatase, leucine, aminopeptidase, succinic dehydrogenase, and indoxyl and nonspecific esterase were positive in the areas of subcutaneous fat necrosis. This is the first report of the association of islet cell carcinoma of the pancreas with generalized subcutaneous fat necrosis.", "contents": "Association of islet cell carcinoma of the pancreas with subcutaneous fat necrosis. A 57-year-old man with generalized, subcutaneous fat necrosis was found at autopsy to have islet cell carcinoma of the pancreas. The histologic diagnosis of islet cell carcinoma was confirmed by the finding by electron microscopy of characteristic intracytoplasmic granules within pancreatic neoplastic cells. Lipase levels were elevated in serum as well as in tissues in areas of subcutaneous fat necrosis. Enzyme histochemical stains for alkaline and acid phosphatase, leucine, aminopeptidase, succinic dehydrogenase, and indoxyl and nonspecific esterase were positive in the areas of subcutaneous fat necrosis. This is the first report of the association of islet cell carcinoma of the pancreas with generalized subcutaneous fat necrosis."}
{"id": "PMID:232387", "title": "Brain's entropy partitions.", "content": "Since the brain processings can be expressed by ballistic or ramp systems, the brain entropy is herein analysed in respect to the distributions of the internal ((MS)1) and external messages ((ME)E) conveyed through the sensory systems. In such a context, it is shown that a first partition (through a primary folding) is established between the neural systems involved in the processings related with the external (RSE) and internal (BSI) environments. Indeed, secondary foldings in both RSE and BSI due to non-homogeneities in (MS)E and (MS)1 are discussed. Finally, the results are extended to the neural phenomena during the brain's embriogenic growth.", "contents": "Brain's entropy partitions. Since the brain processings can be expressed by ballistic or ramp systems, the brain entropy is herein analysed in respect to the distributions of the internal ((MS)1) and external messages ((ME)E) conveyed through the sensory systems. In such a context, it is shown that a first partition (through a primary folding) is established between the neural systems involved in the processings related with the external (RSE) and internal (BSI) environments. Indeed, secondary foldings in both RSE and BSI due to non-homogeneities in (MS)E and (MS)1 are discussed. Finally, the results are extended to the neural phenomena during the brain's embriogenic growth."}
{"id": "PMID:232388", "title": "Kinetic studies of the blood serum xanthine dehydrogenase inhibition by alloxan (2,4,5,6-tetraoxypyrimidine 5,6-dioxyuracil).", "content": "Alloxan is an inhibitor of the enzyme xanthine: NAD+ oxido reductase (E.C.1.2.1.37). Alloxan acts as an electron acceptor and competes \"in vitro\" with the tetrazolium salt used as electron acceptor in the assay system used for the determination of the dehydrogenase activity of the enzyme. The alloxan inhibition was reverted when phenazine methosulfate (PMS) was added to the system.", "contents": "Kinetic studies of the blood serum xanthine dehydrogenase inhibition by alloxan (2,4,5,6-tetraoxypyrimidine 5,6-dioxyuracil). Alloxan is an inhibitor of the enzyme xanthine: NAD+ oxido reductase (E.C.1.2.1.37). Alloxan acts as an electron acceptor and competes \"in vitro\" with the tetrazolium salt used as electron acceptor in the assay system used for the determination of the dehydrogenase activity of the enzyme. The alloxan inhibition was reverted when phenazine methosulfate (PMS) was added to the system."}
{"id": "PMID:232389", "title": "Neurogenic tumors of the head and neck in children.", "content": "A retrospective analysis of deep-seated neurogenic tumors of the head and neck in children seen at the University of Michigan Medical Center was done.  There were 22 patients--10 with plexiform neurofibromas, 3 with neurofibromas, 2 with esthesioneuroblastomas, 2 with neurilemmomas, 1 with neurogenous sarcoma, and 4 with neuroblastomas who presented with a mass in the head and neck.  Delay in diagnosis and treatment was common, and merely allowed the tumor to enlarge.  We feel that surgical extirpation is the preferred treatment for benign or malignant neurogenous tumors, with adjuvant therapy in other forms for malignant tumors only.", "contents": "Neurogenic tumors of the head and neck in children. A retrospective analysis of deep-seated neurogenic tumors of the head and neck in children seen at the University of Michigan Medical Center was done.  There were 22 patients--10 with plexiform neurofibromas, 3 with neurofibromas, 2 with esthesioneuroblastomas, 2 with neurilemmomas, 1 with neurogenous sarcoma, and 4 with neuroblastomas who presented with a mass in the head and neck.  Delay in diagnosis and treatment was common, and merely allowed the tumor to enlarge.  We feel that surgical extirpation is the preferred treatment for benign or malignant neurogenous tumors, with adjuvant therapy in other forms for malignant tumors only."}
{"id": "PMID:232390", "title": "Prophylactic subcutaneous total glandectomy for mammary cystic disease, with immediate primary breast reconstruction.", "content": "Seventeen whole-breast tissue specimens of mammary cystic disease were prepared using Marcum's whole-mounting technique. Histological studies were performed on from 10 to 19 slides of tissue containing the suspected pathological foci. Cysts in the cleared breast tissues were numerous, and cyst walls were covered by single-layered duct epithelial cells with some apocrine metaplasia. The most notable findings were frequent minute carcinomatous foci next to the scattering of mammary cysts. The incidence of carcinoma among 17 mammary cystic disease patients was 8, or 47%. Each patient had from one to six minute carcinomatous foci--less than 1 mm in diameter and noninfiltrating. All patients were treated by subcutaneous total mastectomy and immediate breast reconstruction with the Natural-Y mammary prosthesis. In all 17 the results were good. With no hazardous complications. Steps toward immediate breast reconstruction are as imperative psychologically as the total glandectomy is clinically.", "contents": "Prophylactic subcutaneous total glandectomy for mammary cystic disease, with immediate primary breast reconstruction. Seventeen whole-breast tissue specimens of mammary cystic disease were prepared using Marcum's whole-mounting technique. Histological studies were performed on from 10 to 19 slides of tissue containing the suspected pathological foci. Cysts in the cleared breast tissues were numerous, and cyst walls were covered by single-layered duct epithelial cells with some apocrine metaplasia. The most notable findings were frequent minute carcinomatous foci next to the scattering of mammary cysts. The incidence of carcinoma among 17 mammary cystic disease patients was 8, or 47%. Each patient had from one to six minute carcinomatous foci--less than 1 mm in diameter and noninfiltrating. All patients were treated by subcutaneous total mastectomy and immediate breast reconstruction with the Natural-Y mammary prosthesis. In all 17 the results were good. With no hazardous complications. Steps toward immediate breast reconstruction are as imperative psychologically as the total glandectomy is clinically."}
{"id": "PMID:232391", "title": "Participation of lysine-sensitive aspartokinase in threonine production by S-2-aminoethyl cysteine-resistant mutants of Serratia marcescens.", "content": "S-2-Aminoethyl cysteine (AEC) reduced both growth rate and final growth level of Serratia marcescens Sr41. The growth inhibition was completely reversed by lysine. AEC inhibited the activity of lysine-sensitive aspartokinase to a lesser extent than lysine. The AEC addition to the medium lowered not only the level of lysine-sensite aspartokinase but also those of homoserine dehydrogenase and threonine deaminase, whereas lysine repressed the aspartokinase alone. To select mutations releasing lysine-sensitive aspartokinase from feedback controls, AEC-resistant colonies were isolated from strains HNr31 and HNr53, both of which were previously found to excrete threonine on the minimal plates but not on the plates containing excess lysine. Two of 280 resistant colonies excreted large amounts of threonine. Strains AECr174 and AECr301, derived from strains HNr31 and HNr53, respectively, lacked both feedback inhibition and repression of lysine-sensitive aspartokinase. These strains produced about 7 mg of threonine per ml in the medium containing glucose and urea.", "contents": "Participation of lysine-sensitive aspartokinase in threonine production by S-2-aminoethyl cysteine-resistant mutants of Serratia marcescens. S-2-Aminoethyl cysteine (AEC) reduced both growth rate and final growth level of Serratia marcescens Sr41. The growth inhibition was completely reversed by lysine. AEC inhibited the activity of lysine-sensitive aspartokinase to a lesser extent than lysine. The AEC addition to the medium lowered not only the level of lysine-sensite aspartokinase but also those of homoserine dehydrogenase and threonine deaminase, whereas lysine repressed the aspartokinase alone. To select mutations releasing lysine-sensitive aspartokinase from feedback controls, AEC-resistant colonies were isolated from strains HNr31 and HNr53, both of which were previously found to excrete threonine on the minimal plates but not on the plates containing excess lysine. Two of 280 resistant colonies excreted large amounts of threonine. Strains AECr174 and AECr301, derived from strains HNr31 and HNr53, respectively, lacked both feedback inhibition and repression of lysine-sensitive aspartokinase. These strains produced about 7 mg of threonine per ml in the medium containing glucose and urea."}
{"id": "PMID:232392", "title": "Effect of sample transport systems on survival of bacteria in ground beef.", "content": "The effects of two transport systems and cryoprotective agents on the survival of bacteria in ground beef samples were evaluated. Survival of Clostridium perfringens in ground beef samples after simulated transport (72 h) was higher (about 99%) in Dry Ice than in Trans Temp shipping units (-3 degrees C). There were no significant differences between the two transport systems in survival of coliforms, Escherichia coli, Staphylococcus aureus, or aerobic bacteria. Mixing ground beef samples at a ratio of 1:1 (wt/vol) with 10, 20, or 30% buffered solutions of dimethyl sulfoxide or glycerol before freezing improved the survival of C. perfringens and coliforms in both transport systems. Recovery of E. coli was significantly higher with the addition of 10% dimethyl sulfoxide before Dry Ice transport. Addition of 10% dimethyl sulfoxide resulted in a 100% recovery of both S. aureus and aerobic bacteria from ground beef after simulated transport in Trans Temp shipping units. The use of cryoprotective agents can improve the survival of bacteria during transport of ground beef samples.", "contents": "Effect of sample transport systems on survival of bacteria in ground beef. The effects of two transport systems and cryoprotective agents on the survival of bacteria in ground beef samples were evaluated. Survival of Clostridium perfringens in ground beef samples after simulated transport (72 h) was higher (about 99%) in Dry Ice than in Trans Temp shipping units (-3 degrees C). There were no significant differences between the two transport systems in survival of coliforms, Escherichia coli, Staphylococcus aureus, or aerobic bacteria. Mixing ground beef samples at a ratio of 1:1 (wt/vol) with 10, 20, or 30% buffered solutions of dimethyl sulfoxide or glycerol before freezing improved the survival of C. perfringens and coliforms in both transport systems. Recovery of E. coli was significantly higher with the addition of 10% dimethyl sulfoxide before Dry Ice transport. Addition of 10% dimethyl sulfoxide resulted in a 100% recovery of both S. aureus and aerobic bacteria from ground beef after simulated transport in Trans Temp shipping units. The use of cryoprotective agents can improve the survival of bacteria during transport of ground beef samples."}
{"id": "PMID:232407", "title": "Influence of stimulation of myocardial alpha- as well as beta-adrenoceptors on the effect of digoxin in isolated electrically driven rabbit papillary muscles.", "content": "On isolated electrically driven rabbit papillary muscle the cardiac glycoside digoxin was infused at driving rates of 0.5, 1.0 and 2.0 Hz. Two effective concentrations of digoxin were determined: 1. that inducing the maximal inotropic effect (maximal inotropic concentration) and 2, that causing cardiac arrest (toxic concentration). The influence of the alpha-sympathomimetic drug phenylephrine and for comparison that of the beta-sympathomimetic drug isoprenaline on either concentration of digoxin was investigated. 1. Stimulation of alpha-adrenoceptors by phenylephrine at a rate of 0.5 Hz significantly decreased the maximal inotropic as well as the toxic concentration of digoxin by about 36%; this decrease was maximal under the influence of the EC25 of phenylephrine and could be blocked by phentolamine. Phenylephrine did not alter the maximal inotropic effect of digoxin. At a stimulus rate of 1.0 Hz the EC75 of phenylephrine still diminished significantly the effective concentrations of digoxin whereas under these conditions the EC25 was ineffective. At 2.0 Hz stimulation of myocardial alpha-adrenoceptors had no effect anymore on either the maximal inotropic or the toxic concentration of digoxin. 2. In contrast, stimulation of beta-adrenoceptors by isoprenaline at a driving rate of 2.0 Hz resulted in a pronounced decrease of maximal inotropic and toxic concentration of digoxin while the maximal positive inotropic effect exerted by digoxin was found to be not altered by isoprenaline. The decrease of the effective concentration of digoxin caused by isoprenaline was abolished by pindolol. At a driving rate of 1.0 Hz this effect was slightly attenuated but was completely absent at 0.5 Hz. 3. From these results it can be concluded that stimulation of either adrenoceptor, alpha- and beta-, increases the effectiveness of the cardiac glycoside digoxin, i.e. diminishes the maximal inotropic as well as its toxic concentration. While stimulation of alpha-adrenoceptors is effective only at low rates of stimulation that of beta-adrenoceptors is vice versa at higher ones, thus supporting the view of different mechanisms underlying stimulation of alpha- or beta-adrenoceptors.", "contents": "Influence of stimulation of myocardial alpha- as well as beta-adrenoceptors on the effect of digoxin in isolated electrically driven rabbit papillary muscles. On isolated electrically driven rabbit papillary muscle the cardiac glycoside digoxin was infused at driving rates of 0.5, 1.0 and 2.0 Hz. Two effective concentrations of digoxin were determined: 1. that inducing the maximal inotropic effect (maximal inotropic concentration) and 2, that causing cardiac arrest (toxic concentration). The influence of the alpha-sympathomimetic drug phenylephrine and for comparison that of the beta-sympathomimetic drug isoprenaline on either concentration of digoxin was investigated. 1. Stimulation of alpha-adrenoceptors by phenylephrine at a rate of 0.5 Hz significantly decreased the maximal inotropic as well as the toxic concentration of digoxin by about 36%; this decrease was maximal under the influence of the EC25 of phenylephrine and could be blocked by phentolamine. Phenylephrine did not alter the maximal inotropic effect of digoxin. At a stimulus rate of 1.0 Hz the EC75 of phenylephrine still diminished significantly the effective concentrations of digoxin whereas under these conditions the EC25 was ineffective. At 2.0 Hz stimulation of myocardial alpha-adrenoceptors had no effect anymore on either the maximal inotropic or the toxic concentration of digoxin. 2. In contrast, stimulation of beta-adrenoceptors by isoprenaline at a driving rate of 2.0 Hz resulted in a pronounced decrease of maximal inotropic and toxic concentration of digoxin while the maximal positive inotropic effect exerted by digoxin was found to be not altered by isoprenaline. The decrease of the effective concentration of digoxin caused by isoprenaline was abolished by pindolol. At a driving rate of 1.0 Hz this effect was slightly attenuated but was completely absent at 0.5 Hz. 3. From these results it can be concluded that stimulation of either adrenoceptor, alpha- and beta-, increases the effectiveness of the cardiac glycoside digoxin, i.e. diminishes the maximal inotropic as well as its toxic concentration. While stimulation of alpha-adrenoceptors is effective only at low rates of stimulation that of beta-adrenoceptors is vice versa at higher ones, thus supporting the view of different mechanisms underlying stimulation of alpha- or beta-adrenoceptors."}
{"id": "PMID:232409", "title": "In vitro transformation of primary Chinese hamster cells by minichromosomes from Simian Virus 40.", "content": "Purified SV 40 DNA and SV 40 minichromosomes, either isolated from SV 40 infected cells (NaMi) or reconstituted from viral DNA and the H1 depleted calf thymus histone fraction (ReMi), were tested for their ability to transform primary Chinese hamster lung (CHL) cells. Using the agar suspension technique as the transformation assay, an approximately 200 fold increase in transformation activity for NaMi in comparison with the SV 40 DNA and an approximately 50 fold increased activity in comparison with ReMi could be demonstrated. Uptake experiments suggest that NaMi are taken up quicker and more efficiently from the CHL cells than ReMi or purified DNA. The transforming activity is most significantly using the calcium technique and the infected cells in higher passage numbers. Transformed colonies recovered after infection of CHL cells with SV 40 DNA, NaMi or ReMi revealed SV 40 related T-antigen in 90-100% of the cells tested. The number of T-antigen positive cells was stable over a period of 80 passages. This observation suggest a stable state of transformation by SV 40 DNA and SV 40 minichromosomes.", "contents": "In vitro transformation of primary Chinese hamster cells by minichromosomes from Simian Virus 40. Purified SV 40 DNA and SV 40 minichromosomes, either isolated from SV 40 infected cells (NaMi) or reconstituted from viral DNA and the H1 depleted calf thymus histone fraction (ReMi), were tested for their ability to transform primary Chinese hamster lung (CHL) cells. Using the agar suspension technique as the transformation assay, an approximately 200 fold increase in transformation activity for NaMi in comparison with the SV 40 DNA and an approximately 50 fold increased activity in comparison with ReMi could be demonstrated. Uptake experiments suggest that NaMi are taken up quicker and more efficiently from the CHL cells than ReMi or purified DNA. The transforming activity is most significantly using the calcium technique and the infected cells in higher passage numbers. Transformed colonies recovered after infection of CHL cells with SV 40 DNA, NaMi or ReMi revealed SV 40 related T-antigen in 90-100% of the cells tested. The number of T-antigen positive cells was stable over a period of 80 passages. This observation suggest a stable state of transformation by SV 40 DNA and SV 40 minichromosomes."}
{"id": "PMID:232411", "title": "[Effect of bilateral and unilateral electroconvulsive therapy (ECT) on the composition of the cerebrospinal fluid (CSF). A possibility to calculate the intracellular redox changes of the brain in humans (author's transl)].", "content": "The changes in the composition of CSF and venous blood under the effect of bilateral and unilateral ECT were studied. The intracellular redox changes during the therapy were calculated on the basis of experimental data. Of the patients, 27 were treated with bilateral, another 27 with unilateral ECT. Just before the electroshock, the patients were paralyzed with intravenous succinylcholine chloride and were artificially ventilated with O2. The characteristic change we found was the augmentation of pyruvate concentration in CSF. This change and the calculated shift of NADH/NAD+ ratio in the direction of oxidation refer to the disturbance of the function of enzymes which play a role in the oxidation-reduction processes.", "contents": "[Effect of bilateral and unilateral electroconvulsive therapy (ECT) on the composition of the cerebrospinal fluid (CSF). A possibility to calculate the intracellular redox changes of the brain in humans (author's transl)]. The changes in the composition of CSF and venous blood under the effect of bilateral and unilateral ECT were studied. The intracellular redox changes during the therapy were calculated on the basis of experimental data. Of the patients, 27 were treated with bilateral, another 27 with unilateral ECT. Just before the electroshock, the patients were paralyzed with intravenous succinylcholine chloride and were artificially ventilated with O2. The characteristic change we found was the augmentation of pyruvate concentration in CSF. This change and the calculated shift of NADH/NAD+ ratio in the direction of oxidation refer to the disturbance of the function of enzymes which play a role in the oxidation-reduction processes."}
{"id": "PMID:232412", "title": "Comparison of hemagglutination-inhibition, complement-fixation and enzyme-linked immunosorbent assay for quantitation of human rotavirus antibodies.", "content": "The hemagglutination-inhibition test for detecting rotavirus antibody was evaluated by using simian rotavirus SA-11 as hemagglutinating antigen. Results show that the test is as sensitive as either complement fixation or the enzyme-linked immunosorbent assay for detecting antibody to rotavirus in human sera.", "contents": "Comparison of hemagglutination-inhibition, complement-fixation and enzyme-linked immunosorbent assay for quantitation of human rotavirus antibodies. The hemagglutination-inhibition test for detecting rotavirus antibody was evaluated by using simian rotavirus SA-11 as hemagglutinating antigen. Results show that the test is as sensitive as either complement fixation or the enzyme-linked immunosorbent assay for detecting antibody to rotavirus in human sera."}
{"id": "PMID:232413", "title": "Oncogenic transformation of rat lung epitheloid cells by SV 40 DNA and restriction enzyme fragments.", "content": "Rat epitheloid lung cells were transformed with various preparations of SV40 dna using the Ca2+-precipitation technique. The amount of SV40 genetic information integrated into transformed clones was evaluated by DNA-DNA renaturation kinetics. The growth properties on plastic and in soft-agar were examined, as well as the ability to induce tumors in syngeneic new-born animals or in adult nude mice. One particular transformed line, which had received the Hpa II/BamH I A (59 per cent) fragment, was found to contain about 3 integrated copies of this fragment per cell and no significant amount of the Hpa II/BamH I B (41 per cent) fragment. This line which grew to high saturation densities and efficiently formed clones in low serum on plastic, produced tumors in both syngeneic rats and nude mice. Thus the Hpa II/BamH I A fragment, which mainly includes early viral information, was sufficient to impart these properties to rat epitheloid lung cells.", "contents": "Oncogenic transformation of rat lung epitheloid cells by SV 40 DNA and restriction enzyme fragments. Rat epitheloid lung cells were transformed with various preparations of SV40 dna using the Ca2+-precipitation technique. The amount of SV40 genetic information integrated into transformed clones was evaluated by DNA-DNA renaturation kinetics. The growth properties on plastic and in soft-agar were examined, as well as the ability to induce tumors in syngeneic new-born animals or in adult nude mice. One particular transformed line, which had received the Hpa II/BamH I A (59 per cent) fragment, was found to contain about 3 integrated copies of this fragment per cell and no significant amount of the Hpa II/BamH I B (41 per cent) fragment. This line which grew to high saturation densities and efficiently formed clones in low serum on plastic, produced tumors in both syngeneic rats and nude mice. Thus the Hpa II/BamH I A fragment, which mainly includes early viral information, was sufficient to impart these properties to rat epitheloid lung cells."}
{"id": "PMID:232414", "title": "Nonarbo-togaviridae: comparative hydrodynamic properties of the pestivirus genus. Brief report.", "content": "The sedimentation coefficient and buoyant density of hog cholera, bovine viral diarrhea and Border disease viruses, have been compared with those of representative members of the family togaviridae. It appears that the pestivirus genus is a homogeneous group which is not only antigenically but also structurally, unrelated to the other genera of the togavirus family.", "contents": "Nonarbo-togaviridae: comparative hydrodynamic properties of the pestivirus genus. Brief report. The sedimentation coefficient and buoyant density of hog cholera, bovine viral diarrhea and Border disease viruses, have been compared with those of representative members of the family togaviridae. It appears that the pestivirus genus is a homogeneous group which is not only antigenically but also structurally, unrelated to the other genera of the togavirus family."}
{"id": "PMID:232415", "title": "Development in vitro of cytotoxic lymphocytes against murine cytomegalovirus.", "content": "Lymphocytes cytotoxic for mouse embryo fibroblasts (MEF) infected with murine cytomegalovirus (MCMV) were produced by in vitro culture of \"memory\" spleen cells with UV-irradiated, MCMV-infected, MEF. Cytotoxic lymphocytes were developed from spleen cells of mice 10 to 240 days after infection with MCMV. The cytotoxic cells carried the theta and Ly 2 antigens, and were H-2 restricted in the recognition of infected target cells.", "contents": "Development in vitro of cytotoxic lymphocytes against murine cytomegalovirus. Lymphocytes cytotoxic for mouse embryo fibroblasts (MEF) infected with murine cytomegalovirus (MCMV) were produced by in vitro culture of \"memory\" spleen cells with UV-irradiated, MCMV-infected, MEF. Cytotoxic lymphocytes were developed from spleen cells of mice 10 to 240 days after infection with MCMV. The cytotoxic cells carried the theta and Ly 2 antigens, and were H-2 restricted in the recognition of infected target cells."}
{"id": "PMID:232419", "title": "[Microbiological investigations into soil in a fertilizer trial with spruce in the fume-damaged zone of the Erzgebirge (author's transl)].", "content": "In the heavily fume-damaged spruce stands on crest sites in the eastern parts of Erzgebirge the composition of microbe population and organic matter conversion in the A0 horizon can be positively changed with a lasting effect by fertilization using CaNP. Ammonification, nitrification, urea transformation, and decomposition of cellulose are enhanced by the increased occurrence of bacteria and actinomycetes. As a result of fertilization acidity was reduced from pH (KCl) 3.0 to 3.6 as a maximum. The influence of the nutrient status is clearly manifest in the humus form (raw humus in the case of quartz porphyry, mull-resembling moder in the case of basalt), but scarcely in the chemical and microbiological properties of the Of subhorizon. No pronounced effect of the SO2 fallout on the microbiological conditions in the A0 horizon was observed. The increased soil fertility after application of Ca and P can lead to an increased and a more stable yield of wood only under certain conditions.", "contents": "[Microbiological investigations into soil in a fertilizer trial with spruce in the fume-damaged zone of the Erzgebirge (author's transl)]. In the heavily fume-damaged spruce stands on crest sites in the eastern parts of Erzgebirge the composition of microbe population and organic matter conversion in the A0 horizon can be positively changed with a lasting effect by fertilization using CaNP. Ammonification, nitrification, urea transformation, and decomposition of cellulose are enhanced by the increased occurrence of bacteria and actinomycetes. As a result of fertilization acidity was reduced from pH (KCl) 3.0 to 3.6 as a maximum. The influence of the nutrient status is clearly manifest in the humus form (raw humus in the case of quartz porphyry, mull-resembling moder in the case of basalt), but scarcely in the chemical and microbiological properties of the Of subhorizon. No pronounced effect of the SO2 fallout on the microbiological conditions in the A0 horizon was observed. The increased soil fertility after application of Ca and P can lead to an increased and a more stable yield of wood only under certain conditions."}
{"id": "PMID:232420", "title": "Effect of daily injections of ACTH on growth and on the adrenal and lymphoid tissues of two strains of immature fowls.", "content": "1. The effects of daily injections of ACTH (30 IU/kg) or physiological saline on growth and on adrenal and lymphoid tissues of Rhode Island Red (RIR) and Light Sussex (LS) chickens were compared at 1, 2 and 3 weeks of age. 2. Saline injections retarded skeletal growth in both strains during the 1st week but only affected weight gain in LS birds. 3. Injections of ACTH depressed growth rate, caused adrenal enlargement and deplenished adrenal cholesterol to the same extent in both strains. 4. ACTH caused a greater reduction in bursal size in RIR than in LS birds. Spleen size was reduced by ACTH only in RIR birds. 5. At 2 and 3 weeks the plasma concentrations of corticosterone of RIR birds were greater than those of LS birds. Plasma corticosterone concentrations were within the normal range 24 h after the last injection of ACTH in both strains. 6. Plasma concentrations of growth hormone was unaffected by ACTH treatment in RIR birds, but it was increased in LS birds after 3 weeks of treatment.", "contents": "Effect of daily injections of ACTH on growth and on the adrenal and lymphoid tissues of two strains of immature fowls. 1. The effects of daily injections of ACTH (30 IU/kg) or physiological saline on growth and on adrenal and lymphoid tissues of Rhode Island Red (RIR) and Light Sussex (LS) chickens were compared at 1, 2 and 3 weeks of age. 2. Saline injections retarded skeletal growth in both strains during the 1st week but only affected weight gain in LS birds. 3. Injections of ACTH depressed growth rate, caused adrenal enlargement and deplenished adrenal cholesterol to the same extent in both strains. 4. ACTH caused a greater reduction in bursal size in RIR than in LS birds. Spleen size was reduced by ACTH only in RIR birds. 5. At 2 and 3 weeks the plasma concentrations of corticosterone of RIR birds were greater than those of LS birds. Plasma corticosterone concentrations were within the normal range 24 h after the last injection of ACTH in both strains. 6. Plasma concentrations of growth hormone was unaffected by ACTH treatment in RIR birds, but it was increased in LS birds after 3 weeks of treatment."}
{"id": "PMID:232426", "title": "The efficacy of two commercial feline rhinotracheitis-calicivirus-panleukopenia vaccines.", "content": "The efficacy of two commercial feline vaccines was determined by challenging vaccinated and unvaccinated cats sequentially with a virulent feline calicivirus and rhinotracheitis virus. Serological responses to these viruses as well as to panleuk openia virus were also measured. Results show significant protection and satisfactory serological responses are conferred by both vaccines. One vaccine showed significant superiority in protection against feline viral rhinotracheitis.", "contents": "The efficacy of two commercial feline rhinotracheitis-calicivirus-panleukopenia vaccines. The efficacy of two commercial feline vaccines was determined by challenging vaccinated and unvaccinated cats sequentially with a virulent feline calicivirus and rhinotracheitis virus. Serological responses to these viruses as well as to panleuk openia virus were also measured. Results show significant protection and satisfactory serological responses are conferred by both vaccines. One vaccine showed significant superiority in protection against feline viral rhinotracheitis."}
{"id": "PMID:232427", "title": "Uridine kinase activity in human tumors.", "content": "The activity of uridine kinase, a key enzyme in the salvage pathway for pyrimidine bases and nucleosides and for the activation of the corresponding chemotherapeutic analogs, varied 10-fold in a series of human colon adenosarcomas; similar variations were observed with other tumor types. In contrast to the leukemias where only the adult isozyme appears to be present, both the adult and embryonic forms were present in the solid tumors examined. The qualitative and quantitative differences may account, in part, for differences in the innate (initial) sensitivity of the tumors to pyrimidine base and nucleoside analogs.", "contents": "Uridine kinase activity in human tumors. The activity of uridine kinase, a key enzyme in the salvage pathway for pyrimidine bases and nucleosides and for the activation of the corresponding chemotherapeutic analogs, varied 10-fold in a series of human colon adenosarcomas; similar variations were observed with other tumor types. In contrast to the leukemias where only the adult isozyme appears to be present, both the adult and embryonic forms were present in the solid tumors examined. The qualitative and quantitative differences may account, in part, for differences in the innate (initial) sensitivity of the tumors to pyrimidine base and nucleoside analogs."}
{"id": "PMID:232428", "title": "Nor-MDP, saponin, corynebacteria, and pertussis organisms as immunological adjuvants in experimental malaria vaccination of macaques.", "content": "Vaccination of primates against malaria using antigen derived from erythrocytic parasite stages has been most successful where Freund's complete adjuvant has been employed. Since this adjuvant is clinically unacceptable its replacement is a matter of urgency.In the present work a muramyldipeptide derivative (nor-MDP) given in mineral oil has proved to be partially effective as an adjuvant for merozoite vaccination of Macaca mulatta against Plasmodium knowlesi, and saponin has proved to be effective in similar vaccination of M. fascicularis.", "contents": "Nor-MDP, saponin, corynebacteria, and pertussis organisms as immunological adjuvants in experimental malaria vaccination of macaques. Vaccination of primates against malaria using antigen derived from erythrocytic parasite stages has been most successful where Freund's complete adjuvant has been employed. Since this adjuvant is clinically unacceptable its replacement is a matter of urgency.In the present work a muramyldipeptide derivative (nor-MDP) given in mineral oil has proved to be partially effective as an adjuvant for merozoite vaccination of Macaca mulatta against Plasmodium knowlesi, and saponin has proved to be effective in similar vaccination of M. fascicularis."}
{"id": "PMID:232429", "title": "[5-Bromodeoxyuridine inhibition of the transformation of Rous sarcoma virus-infected chicken cells].", "content": "The transformation of Rous-Sarcoma-Virus-infected synchronized Chicken cells is prevented when 5-bromodeoxyuridine is added for 3 hrs. at time of the peak of the first S phase following infection. Virus progeny is normally released. The inhibitory effect of BrdU is reversed by simultaneous addition of thymidine, but not by that of deoxyuridine. Hence, the inhibition of the transformation seems to result from the incorporation of the analogue into the nuclear DNA.", "contents": "[5-Bromodeoxyuridine inhibition of the transformation of Rous sarcoma virus-infected chicken cells]. The transformation of Rous-Sarcoma-Virus-infected synchronized Chicken cells is prevented when 5-bromodeoxyuridine is added for 3 hrs. at time of the peak of the first S phase following infection. Virus progeny is normally released. The inhibitory effect of BrdU is reversed by simultaneous addition of thymidine, but not by that of deoxyuridine. Hence, the inhibition of the transformation seems to result from the incorporation of the analogue into the nuclear DNA."}
{"id": "PMID:232430", "title": "[Involvement of endorphins in the emotional behavior of pigs].", "content": "Social isolation and exposure to a new environment induce hyperactivity, vocalizations and ACTH release in weaned Piglets acutely submitted to this stress. These reactions are increased by pretreatment with morphine (0.5 and 1 mg/kg) and decreased by naloxone (1 mg/kg), suggesting that endogenous opiates modulate emotional behaviour in Pigs.", "contents": "[Involvement of endorphins in the emotional behavior of pigs]. Social isolation and exposure to a new environment induce hyperactivity, vocalizations and ACTH release in weaned Piglets acutely submitted to this stress. These reactions are increased by pretreatment with morphine (0.5 and 1 mg/kg) and decreased by naloxone (1 mg/kg), suggesting that endogenous opiates modulate emotional behaviour in Pigs."}
{"id": "PMID:232432", "title": "Reliability and reproducibility of interpretation of 99mtechnetium pyrophosphate myocardial scintigrams.", "content": "The interpretations of 156 99mtechnetium pyrophosphate myocardial scintigrams by four observers were analyzed in order to determine the reliability and reproducibility of the subjective process of reading scintigrams. The scintigrams were scored on an integral scale from 0 to 4, depending upon the degree of myocardial radionuclide accumulation, and the site and nature of uptake were specified. Exact agreement upon score was generally poor but approximate concurrence of interpretation was good (90.4 and 92.5% inter- and intra-observer agreement, respectively). There was somewhat less agreement on scintigrams with the higher scores of 3 and 4 (83.3 and 78.0%, respectively). A high level of concurrence upon the differentiation between diffuse and localized uptake, and upon the site of uptake, was found. We conclude that only approximate rather than exact agreement of individual readers' interpretations can be expected in this subjective technique, that scintigrams with higher degrees of radionuclide accumulation produce slightly greater observer disagreement, and that variability of interpretation could account for some of the diagnostic inaccuracy of 99mtechnetium pyrophosphate myocardial scintigraphy.", "contents": "Reliability and reproducibility of interpretation of 99mtechnetium pyrophosphate myocardial scintigrams. The interpretations of 156 99mtechnetium pyrophosphate myocardial scintigrams by four observers were analyzed in order to determine the reliability and reproducibility of the subjective process of reading scintigrams. The scintigrams were scored on an integral scale from 0 to 4, depending upon the degree of myocardial radionuclide accumulation, and the site and nature of uptake were specified. Exact agreement upon score was generally poor but approximate concurrence of interpretation was good (90.4 and 92.5% inter- and intra-observer agreement, respectively). There was somewhat less agreement on scintigrams with the higher scores of 3 and 4 (83.3 and 78.0%, respectively). A high level of concurrence upon the differentiation between diffuse and localized uptake, and upon the site of uptake, was found. We conclude that only approximate rather than exact agreement of individual readers' interpretations can be expected in this subjective technique, that scintigrams with higher degrees of radionuclide accumulation produce slightly greater observer disagreement, and that variability of interpretation could account for some of the diagnostic inaccuracy of 99mtechnetium pyrophosphate myocardial scintigraphy."}
{"id": "PMID:232439", "title": "Metabolism of low density lipoproteins in human fibroblast culture.", "content": "The purpose of the study was to investigate the changes which low density lipoproteins (LDL) underwent during incubation with human culture fibroblasts. The results showed a predominant deposition of lipids, a low level of LDL-protein breakdown products in the cells, the altered structure of lipoproteins, absorbed on the cell surface and of lipoproteins in the incubation medium. The authors suppose intensive metabolic transformations to take place on the cell membrane. The partial lipoprotein degradation seems to realize favourable conditions for the subsequent entry of lipids into the cells and for a pinocytosis of lipoprotein particles transformed on the cell surface. The intensity of these membrane metabolic transformations is influenced by the antigenic properties of LDL, the presence of other proteins in the medium, and by the maturity and the metabolic activity of the cultured cells.", "contents": "Metabolism of low density lipoproteins in human fibroblast culture. The purpose of the study was to investigate the changes which low density lipoproteins (LDL) underwent during incubation with human culture fibroblasts. The results showed a predominant deposition of lipids, a low level of LDL-protein breakdown products in the cells, the altered structure of lipoproteins, absorbed on the cell surface and of lipoproteins in the incubation medium. The authors suppose intensive metabolic transformations to take place on the cell membrane. The partial lipoprotein degradation seems to realize favourable conditions for the subsequent entry of lipids into the cells and for a pinocytosis of lipoprotein particles transformed on the cell surface. The intensity of these membrane metabolic transformations is influenced by the antigenic properties of LDL, the presence of other proteins in the medium, and by the maturity and the metabolic activity of the cultured cells."}
{"id": "PMID:232441", "title": "Brain opiate receptor concentrations are increased in adult spontaneously hypertensive rats.", "content": "The saturable binding of 3H-naltrexone in the brains of eight week old spontaneously hypertensive rats (SHR) is about twice that measured in corresponding normotensive WKY rats. This increase is dependent on age since in three and four week old SHR and WKY rats no difference in binding is observed. Scatchard analysis of the saturation curves for the adult animals revealed that the change in binding is due to an increase in the number of binding sites and does not reflect a difference in binding affinity. The increase in opiate receptor content of SHR rats coincides with the appearance of elevated blood pressure in these animals, and supports a concept in which an interaction between the endorphins and the endocrine system may be involved in the mechanisms controlling hypertension.", "contents": "Brain opiate receptor concentrations are increased in adult spontaneously hypertensive rats. The saturable binding of 3H-naltrexone in the brains of eight week old spontaneously hypertensive rats (SHR) is about twice that measured in corresponding normotensive WKY rats. This increase is dependent on age since in three and four week old SHR and WKY rats no difference in binding is observed. Scatchard analysis of the saturation curves for the adult animals revealed that the change in binding is due to an increase in the number of binding sites and does not reflect a difference in binding affinity. The increase in opiate receptor content of SHR rats coincides with the appearance of elevated blood pressure in these animals, and supports a concept in which an interaction between the endorphins and the endocrine system may be involved in the mechanisms controlling hypertension."}
{"id": "PMID:232442", "title": "Multiplication stimulating activity regulates ornithine decarboxylase in isolated porcine granulosa cells in vitro.", "content": "The polypeptide growth factor, multiplication stimulating activity (MSA), stimulates ornithine decarboxylase (ODC) activity in isolated porcine granulosa cells maintained under chemically defined conditions in vitro. The stimulatory action of MSA is saturable, and dose-dependent (0.1-1000 ng/ml). MSA effects are additive to those of luteinizing hormone (LH), but not those of follicle stimulating hormone (FSH). Stimulation of ODC activity by MSA requires cellular protein and RNA synthesis, and appears to be mediated independently of cyclic AMP. These observations provide the first demonstration of MSA action in the mammalian ovary.", "contents": "Multiplication stimulating activity regulates ornithine decarboxylase in isolated porcine granulosa cells in vitro. The polypeptide growth factor, multiplication stimulating activity (MSA), stimulates ornithine decarboxylase (ODC) activity in isolated porcine granulosa cells maintained under chemically defined conditions in vitro. The stimulatory action of MSA is saturable, and dose-dependent (0.1-1000 ng/ml). MSA effects are additive to those of luteinizing hormone (LH), but not those of follicle stimulating hormone (FSH). Stimulation of ODC activity by MSA requires cellular protein and RNA synthesis, and appears to be mediated independently of cyclic AMP. These observations provide the first demonstration of MSA action in the mammalian ovary."}
{"id": "PMID:232444", "title": "[Factor(s) controlling the secretion of adrenocorticotropin (ACTH) in peripheral plasma (author's transl)].", "content": "The factor(s) controlling the secretion of ACTH in peripheral plasma are not well known. The effects of non-extracted and extracted plasma on ACTH secretion were investigated using rat anterior pituitary cell cultures. Medium ACTH was assayed by radioimmunoassay, and the corticotropin releasing activity (CRA) was expressed as ACTH released. One hundred ul of non-extracted plasma showed significant CRA, whereas greater volumes of plasma showed reduced activity. Non-extracted plasma (250 approximately 500 microliter) rather reduced the secretion of ACTH evoked by hypothalamic extract (HE). When plasma was extracted with 0.2 N-acetic acid-acetone and divided into an acid phase and an acetone-ether phase by adding ether, the CRA was recovered in the acid phase while no significant activity was observed in the acetone-ether phase. The acid phase extract of plasma showed a positive dose-response relationship between the amount of plasma extract (50 approximately 800 microliter plasma equivalent) and ACTH release in pituitary cell cultures. The organic phase of plasma extract inhibited HE-induced release of ACTH, and this ACTH-release inhibiting activity was presumed to be corticosterone. When the acid phase extract of 20 ml plasma was applied to a Sephadex G-25 (fine) and eluted with 0.2 N acetic acid, two peaks of CRA were observed. One eluted in the region of void volume and another eluted in the retarded region where no activity was found in chromatography of HE. HE increased both ACTH and cyclic AMP release, but the plasma extract reduced cyclic AMP release. These results suggest that plasma contains both CRA and ACTH release inhibiting activity which can be extracted separately, and that plasma CRA is different from the hypothalamic corticotropin releasing factor.", "contents": "[Factor(s) controlling the secretion of adrenocorticotropin (ACTH) in peripheral plasma (author's transl)]. The factor(s) controlling the secretion of ACTH in peripheral plasma are not well known. The effects of non-extracted and extracted plasma on ACTH secretion were investigated using rat anterior pituitary cell cultures. Medium ACTH was assayed by radioimmunoassay, and the corticotropin releasing activity (CRA) was expressed as ACTH released. One hundred ul of non-extracted plasma showed significant CRA, whereas greater volumes of plasma showed reduced activity. Non-extracted plasma (250 approximately 500 microliter) rather reduced the secretion of ACTH evoked by hypothalamic extract (HE). When plasma was extracted with 0.2 N-acetic acid-acetone and divided into an acid phase and an acetone-ether phase by adding ether, the CRA was recovered in the acid phase while no significant activity was observed in the acetone-ether phase. The acid phase extract of plasma showed a positive dose-response relationship between the amount of plasma extract (50 approximately 800 microliter plasma equivalent) and ACTH release in pituitary cell cultures. The organic phase of plasma extract inhibited HE-induced release of ACTH, and this ACTH-release inhibiting activity was presumed to be corticosterone. When the acid phase extract of 20 ml plasma was applied to a Sephadex G-25 (fine) and eluted with 0.2 N acetic acid, two peaks of CRA were observed. One eluted in the region of void volume and another eluted in the retarded region where no activity was found in chromatography of HE. HE increased both ACTH and cyclic AMP release, but the plasma extract reduced cyclic AMP release. These results suggest that plasma contains both CRA and ACTH release inhibiting activity which can be extracted separately, and that plasma CRA is different from the hypothalamic corticotropin releasing factor."}
{"id": "PMID:232448", "title": "Stability of IgG solutions, especially anti-D gammaglobulin, with special reference to measured proteolytic activity and degradation.", "content": "The stability of IgG solutions during the dating period can be predicted by measuring the degree of degradation after elevated storage conditions at +37 degrees C with added streptokinase. The measurement of proteolytic activity with a synthetic substrate correlates with the results obtained by SDS-disc gel electrophoresis and gel filtration. IgG molecules having Anti-D activity were observed to be essentially more sensitive to proteolytic degradation by plasmin than IgG molecules in general. It seems, therefore, that the methods which are suitable for the study of the stability of normal IgG preparations are not sufficient to predict the stability of anti-D gammaglobulin preparations.", "contents": "Stability of IgG solutions, especially anti-D gammaglobulin, with special reference to measured proteolytic activity and degradation. The stability of IgG solutions during the dating period can be predicted by measuring the degree of degradation after elevated storage conditions at +37 degrees C with added streptokinase. The measurement of proteolytic activity with a synthetic substrate correlates with the results obtained by SDS-disc gel electrophoresis and gel filtration. IgG molecules having Anti-D activity were observed to be essentially more sensitive to proteolytic degradation by plasmin than IgG molecules in general. It seems, therefore, that the methods which are suitable for the study of the stability of normal IgG preparations are not sufficient to predict the stability of anti-D gammaglobulin preparations."}
{"id": "PMID:232451", "title": "Unidirectional gene conversion associated with two insertions in neurospora crassa mitochondrial DNA.", "content": "The mitochondrial phenotype of [poky] and other extranuclear Neurospora mutants is known to predominate over that of wild type in heteroplasmons. In the present work, we have investigated the interaction between wild-type and [poky] mtDNAs using as many as four physical markers to distinguish the two types of mtDNAs. Two insertions, one of 1200 bp in Eco RI-5 and the other 50 bp in Eco RI-9, are identified as sites of high frequency, unidirectional gene conversion leading to their spread through mtDNA populations in heteroplasmons. However, the transmission of the [poky] mutation does not appear to be correlated with the transmission of either of these insertions or of other physical markers. The possibility that other loci of nonreciprocal recombination might be responsible for the \"dominance\" of Neurospora extranuclear mutants is discussed.", "contents": "Unidirectional gene conversion associated with two insertions in neurospora crassa mitochondrial DNA. The mitochondrial phenotype of [poky] and other extranuclear Neurospora mutants is known to predominate over that of wild type in heteroplasmons. In the present work, we have investigated the interaction between wild-type and [poky] mtDNAs using as many as four physical markers to distinguish the two types of mtDNAs. Two insertions, one of 1200 bp in Eco RI-5 and the other 50 bp in Eco RI-9, are identified as sites of high frequency, unidirectional gene conversion leading to their spread through mtDNA populations in heteroplasmons. However, the transmission of the [poky] mutation does not appear to be correlated with the transmission of either of these insertions or of other physical markers. The possibility that other loci of nonreciprocal recombination might be responsible for the \"dominance\" of Neurospora extranuclear mutants is discussed."}
{"id": "PMID:232452", "title": "Site-specific instability in Drosophila melanogaster: the origin of the mutation and cytogenetic evidence for site specificity.", "content": "During a study of delayed mutations, an unstable X chromosome (Uc) was detected. Spontaneous X-linked recessive lethal mutations were detected in 34 of 993 sperm sampled from 50 males carrying this chromosome. All but three of the 34 lethals originated as clusters in three of the 50 males Cytogenetic and complementation analyses revealed 14 intrachromosomal rearrangements: ten inversions, two reverse repeats, one deficiency and one transposition. Eight of the 14 rearrangements have one break in the 6F1-2 doublet and two rearrangements have a break in 6F1-5 of the X chromosome. The remaining four rearrangements have in addition to the aberrations a lethal point mutation between 6F1 and 6F5. Though each of the lethal lines was established from a single lethal-bearing female, chromosome polymorphism is evident in 17 of the 18 lines having rearrangements, with certain aberrations recurring in several lines. The lethal mutations revert frequently to the nonlethal state, and cytological evidence indicates that more than one mutational event may occur at the unstable locus of the chromosome during one generation. Two lethal lines had more than one type of chromosome rearrangement sharing a common breakpoint. These observations are consistent with the view that the instability of the Uc lines is caused by a transposable element capable of site-specific chromosome breaks and perpetual generation of mutations. The mutagenic and genetic properties of transposable elements can be related to the two-mutation theory of KNUDSON (1971) for cancer initiation.", "contents": "Site-specific instability in Drosophila melanogaster: the origin of the mutation and cytogenetic evidence for site specificity. During a study of delayed mutations, an unstable X chromosome (Uc) was detected. Spontaneous X-linked recessive lethal mutations were detected in 34 of 993 sperm sampled from 50 males carrying this chromosome. All but three of the 34 lethals originated as clusters in three of the 50 males Cytogenetic and complementation analyses revealed 14 intrachromosomal rearrangements: ten inversions, two reverse repeats, one deficiency and one transposition. Eight of the 14 rearrangements have one break in the 6F1-2 doublet and two rearrangements have a break in 6F1-5 of the X chromosome. The remaining four rearrangements have in addition to the aberrations a lethal point mutation between 6F1 and 6F5. Though each of the lethal lines was established from a single lethal-bearing female, chromosome polymorphism is evident in 17 of the 18 lines having rearrangements, with certain aberrations recurring in several lines. The lethal mutations revert frequently to the nonlethal state, and cytological evidence indicates that more than one mutational event may occur at the unstable locus of the chromosome during one generation. Two lethal lines had more than one type of chromosome rearrangement sharing a common breakpoint. These observations are consistent with the view that the instability of the Uc lines is caused by a transposable element capable of site-specific chromosome breaks and perpetual generation of mutations. The mutagenic and genetic properties of transposable elements can be related to the two-mutation theory of KNUDSON (1971) for cancer initiation."}
{"id": "PMID:232456", "title": "Anatomy of the RNA and gene products of MC29 and MH2, two defective avian tumor viruses causing acute leukemia and carcinoma: evidence for a new class of transforming genes.", "content": "The RNA species of the defective avian acute leukemia virus MC29 and of the defective avian carcinoma virus MH2 and of their helper viruses were analyzed using gel electrophoresis, fingerprinting of RNase T1-resistant oligonucleotides, RNA-cDNA hybridization and in vitro translation. A28S RNA species, of 5700 nucleotides, was identified as MC29- or MH2-specific. MC29 RNA shared 4 out of about 17 and MH2 RNA at least 1 out of 16 T1-oligonucleotides with several other avain tumor virus RNAs. In addition MC29 and MH2 RNAs shared 2 oligonucleotides which were not found in any other viral RNA tested. 60% of each 28S RNA could be hybridized by DNA complementary to other avian tumor virus RNAs (group-specific) but 40% could only be hybridized by homologous cDNA (specific). Src gene-related sequences of Rous sarcoma virus were not found in MC29 or MH2 RNA. The specific and group-specific sequences of MC29, defined in terms of their T1-oligonucleotides, were located on a map of all T1-oligonucleotides of viral RNA. Specific sequences mapped between 0,4 and 0,7 map units from the 3'poly(A) end and group-specific sequences mapped between 0 and 0,4 and 0,7 and 1 map units. The MC29-specific RNA segment was represented by 6 oligonucleotides, two of which were those shared only by MC29 and MH2 RNAs. In vitro translation of MC29 RNA generated a major 120 000 dalton protein and minor 56 000 and 37 000 dalton proteins. The 120 000 dalton protein shared sequences with the proteins of the avian tumor viral gag gene, which maps at the 5' end of independently replicating viruses. Since a gag gene-related oligonucleotide was also found near the 5' end of MC29 RNA, we propose that the 120 000 MC29 protein was translated from the 5' 60% of MC29 RNA. It would then include sequences of the defective gag gene as well as MC29-specific sequences. Since both MC29 and MH2 lack the src (sarcoma) gene of Rous sarcoma virusk it is concluded that they contain a distinct class of transforming (onc) genes. We propose that the specific sequences of MC29 and MH2 represent all, or part of, their onc genes because the onc genes of MC29 and MH2 are specific and represent the only known genetic function of these viruses. If this proposal is correct, the onc genes of MC29 and MH2 would be related, because the specific RNA sequence of MC29 shares 2 of 6 oligonucleotides with MH2. It would also follow that the 120 000 dalton MC29 protein is a probable onc gene product, because it is translated from MC29-specific (and group-specific) sequences and because both MC29- and MH2-transformed cells contain specific 120 000 and 100 000 dalton proteins, respectively.", "contents": "Anatomy of the RNA and gene products of MC29 and MH2, two defective avian tumor viruses causing acute leukemia and carcinoma: evidence for a new class of transforming genes. The RNA species of the defective avian acute leukemia virus MC29 and of the defective avian carcinoma virus MH2 and of their helper viruses were analyzed using gel electrophoresis, fingerprinting of RNase T1-resistant oligonucleotides, RNA-cDNA hybridization and in vitro translation. A28S RNA species, of 5700 nucleotides, was identified as MC29- or MH2-specific. MC29 RNA shared 4 out of about 17 and MH2 RNA at least 1 out of 16 T1-oligonucleotides with several other avain tumor virus RNAs. In addition MC29 and MH2 RNAs shared 2 oligonucleotides which were not found in any other viral RNA tested. 60% of each 28S RNA could be hybridized by DNA complementary to other avian tumor virus RNAs (group-specific) but 40% could only be hybridized by homologous cDNA (specific). Src gene-related sequences of Rous sarcoma virus were not found in MC29 or MH2 RNA. The specific and group-specific sequences of MC29, defined in terms of their T1-oligonucleotides, were located on a map of all T1-oligonucleotides of viral RNA. Specific sequences mapped between 0,4 and 0,7 map units from the 3'poly(A) end and group-specific sequences mapped between 0 and 0,4 and 0,7 and 1 map units. The MC29-specific RNA segment was represented by 6 oligonucleotides, two of which were those shared only by MC29 and MH2 RNAs. In vitro translation of MC29 RNA generated a major 120 000 dalton protein and minor 56 000 and 37 000 dalton proteins. The 120 000 dalton protein shared sequences with the proteins of the avian tumor viral gag gene, which maps at the 5' end of independently replicating viruses. Since a gag gene-related oligonucleotide was also found near the 5' end of MC29 RNA, we propose that the 120 000 MC29 protein was translated from the 5' 60% of MC29 RNA. It would then include sequences of the defective gag gene as well as MC29-specific sequences. Since both MC29 and MH2 lack the src (sarcoma) gene of Rous sarcoma virusk it is concluded that they contain a distinct class of transforming (onc) genes. We propose that the specific sequences of MC29 and MH2 represent all, or part of, their onc genes because the onc genes of MC29 and MH2 are specific and represent the only known genetic function of these viruses. If this proposal is correct, the onc genes of MC29 and MH2 would be related, because the specific RNA sequence of MC29 shares 2 of 6 oligonucleotides with MH2. It would also follow that the 120 000 dalton MC29 protein is a probable onc gene product, because it is translated from MC29-specific (and group-specific) sequences and because both MC29- and MH2-transformed cells contain specific 120 000 and 100 000 dalton proteins, respectively."}
{"id": "PMID:232458", "title": "The in vitro of Rous sarcoma virus RNA and function of the viral protein during the viral replication.", "content": "The gag gene and pol gene of the Rous sarcoma virus are translated in vitro from the 35S viral RNA. The env gene cannot be translated in vitro from the 35S RNA. For the in vitro translation of the src gene. 3' end fragments of the viral RNA are used. The gag protein p15 has a proteolytic activity and specifically processes its own protein precursor pr76. The gag protein p19 suppresses the in vitro translation of the pol gene.", "contents": "The in vitro of Rous sarcoma virus RNA and function of the viral protein during the viral replication. The gag gene and pol gene of the Rous sarcoma virus are translated in vitro from the 35S viral RNA. The env gene cannot be translated in vitro from the 35S RNA. For the in vitro translation of the src gene. 3' end fragments of the viral RNA are used. The gag protein p15 has a proteolytic activity and specifically processes its own protein precursor pr76. The gag protein p19 suppresses the in vitro translation of the pol gene."}
{"id": "PMID:232460", "title": "Effect of vitamin A on plasminogen activator synthesis by chick embryo fibroblasts.", "content": "Low concentrations of Vitamin A stimulated plasminogen activator synthesis (PA) in chick embryo fibroblasts (CEF). It caused a dose dependent and reversible increase in PA synthesis in both normal CEF and CEF infected with a temperature sensitive mutant of Rous Sarcoma virus (RSV-Ts68). Both induction and deinduction of PA could be inhibited by Actinomycin D. Vitamin A also accentuated the morphological changes associated with transformation in the Rous Sarcoma virus infected cells. The effects of Vitamin A on PA synthesis were essentially similar to those of the known tumour promoter, phorbol myristate acetate (PMA). Both Vitamin A and PMA were found to act synergistically with sarcoma gene expression as far as PA synthesis was concerned.", "contents": "Effect of vitamin A on plasminogen activator synthesis by chick embryo fibroblasts. Low concentrations of Vitamin A stimulated plasminogen activator synthesis (PA) in chick embryo fibroblasts (CEF). It caused a dose dependent and reversible increase in PA synthesis in both normal CEF and CEF infected with a temperature sensitive mutant of Rous Sarcoma virus (RSV-Ts68). Both induction and deinduction of PA could be inhibited by Actinomycin D. Vitamin A also accentuated the morphological changes associated with transformation in the Rous Sarcoma virus infected cells. The effects of Vitamin A on PA synthesis were essentially similar to those of the known tumour promoter, phorbol myristate acetate (PMA). Both Vitamin A and PMA were found to act synergistically with sarcoma gene expression as far as PA synthesis was concerned."}
{"id": "PMID:232467", "title": "Chromosome abnormalities in leukemia.", "content": "The consistent occurrence of nonrandom chromosome changes in human malignancies suggests that they are not trivial epiphonomena. Whereas we do not understand their significance at present, one possible role which they may fulfill is to provide the chromosomally aberrant cells with a proliferative advantage as the result of alteration in the number or location of genes related to nucleic acid biosynthesis. The proliferative advantage provided by various chromosome aberrations is likely to differ in patients with different genetic constitutions.", "contents": "Chromosome abnormalities in leukemia. The consistent occurrence of nonrandom chromosome changes in human malignancies suggests that they are not trivial epiphonomena. Whereas we do not understand their significance at present, one possible role which they may fulfill is to provide the chromosomally aberrant cells with a proliferative advantage as the result of alteration in the number or location of genes related to nucleic acid biosynthesis. The proliferative advantage provided by various chromosome aberrations is likely to differ in patients with different genetic constitutions."}
{"id": "PMID:232469", "title": "Leukemia specific antigens: FOCMA and immune surveillance.", "content": "In cats, horizontally transmitted viruses cause leukemia and lymphoma under natural conditions. As with other retroviruses, feline leukemia virus (FeLV) contains products of 3 major genes; the virus core gag gene products, the polymerase, and the virus envelope glycoprotein. When cells are transformed in vitro by the related feline sarcoma virus (FeSV), an additional protein, FOCMA is expressed at the cell membrane. FOCMA, which is FeSV-coded, is transformation and/or tumor specific and expressed regardless of whether or not the cells make virus or contain virus structural antigens. Lymphoid leukemia cells also express FOCMA, both when FeLV is used to induce the disease in laboratory cats and when the tumors occur under natural conditions. FOCMA is expressed on both T and B lymphoid leukemia cells, but not expressed on non-malignant lymphoid cells, even when they are infected with FeLV. About one-third of the naturally occurring lymphoid tumors of cats lack detectable FeLV proteins and varying portions of the FeLV provirus. Despite this, they regularly express FOCMA, which is the target of an immuno-surveillance response that functions effectively under most conditions. FOCMA thus provides a useful model for antigens that might be expressed in \"virus-negative\" leukemias of man.", "contents": "Leukemia specific antigens: FOCMA and immune surveillance. In cats, horizontally transmitted viruses cause leukemia and lymphoma under natural conditions. As with other retroviruses, feline leukemia virus (FeLV) contains products of 3 major genes; the virus core gag gene products, the polymerase, and the virus envelope glycoprotein. When cells are transformed in vitro by the related feline sarcoma virus (FeSV), an additional protein, FOCMA is expressed at the cell membrane. FOCMA, which is FeSV-coded, is transformation and/or tumor specific and expressed regardless of whether or not the cells make virus or contain virus structural antigens. Lymphoid leukemia cells also express FOCMA, both when FeLV is used to induce the disease in laboratory cats and when the tumors occur under natural conditions. FOCMA is expressed on both T and B lymphoid leukemia cells, but not expressed on non-malignant lymphoid cells, even when they are infected with FeLV. About one-third of the naturally occurring lymphoid tumors of cats lack detectable FeLV proteins and varying portions of the FeLV provirus. Despite this, they regularly express FOCMA, which is the target of an immuno-surveillance response that functions effectively under most conditions. FOCMA thus provides a useful model for antigens that might be expressed in \"virus-negative\" leukemias of man."}
{"id": "PMID:232475", "title": "Detection of integrated type-C viral DNA fragments in two primates (human and gibbon) by the restriction enzyme blotting technique.", "content": "We have shown that 1. partial provirus integration can be a possible result of a natural infection, and may serve as a model in animal systems where a viral etiology is implicated but detection of a major fraction of the virus genome is rare; 2. All human DNA contains some sequences that hybridize specifically with genomes of SiSV-SiSAV, suggesting that viruses of this group have infected humans in the past and recombined with human cellular DNA. 3. Finally, DNA from uncultured leukocytes of two leukemic patients, one being HL23, which yielded the virus HL23V in culture, was shown to have virus specific fragments related to BaEV. Another human DNA sample revealed virus specific fragments related to SiSV(SiSAV). These fragments are probably acquired by infection.", "contents": "Detection of integrated type-C viral DNA fragments in two primates (human and gibbon) by the restriction enzyme blotting technique. We have shown that 1. partial provirus integration can be a possible result of a natural infection, and may serve as a model in animal systems where a viral etiology is implicated but detection of a major fraction of the virus genome is rare; 2. All human DNA contains some sequences that hybridize specifically with genomes of SiSV-SiSAV, suggesting that viruses of this group have infected humans in the past and recombined with human cellular DNA. 3. Finally, DNA from uncultured leukocytes of two leukemic patients, one being HL23, which yielded the virus HL23V in culture, was shown to have virus specific fragments related to BaEV. Another human DNA sample revealed virus specific fragments related to SiSV(SiSAV). These fragments are probably acquired by infection."}
{"id": "PMID:232478", "title": "Calcium regulation in the myometrium of pregnant sheep.", "content": "Fractionation of pregnant sheep myometrium has been carried out and the fractions obtained analysed for their marker enzyme content and Ca2+ transporting properties. A fairly pure mitochondrial fraction and a very pure plasma membrane fraction were obtained. Both fractions could accumulate Ca2+ in the presence of ATP but the mechanisms were different, mitochondrial uptake had a high capacity and was inhibited by azide. Plasma membrane uptake was of low capacity and unaffected by azide. The effect of oxalate on plasma membrane suggests that there is an outwardly directed Ca2+ pump in the myometrial cell membrane. Both mitochondria and plasma membrane may be important in the Cas2+ accumulation of relaxation in this muscle.", "contents": "Calcium regulation in the myometrium of pregnant sheep. Fractionation of pregnant sheep myometrium has been carried out and the fractions obtained analysed for their marker enzyme content and Ca2+ transporting properties. A fairly pure mitochondrial fraction and a very pure plasma membrane fraction were obtained. Both fractions could accumulate Ca2+ in the presence of ATP but the mechanisms were different, mitochondrial uptake had a high capacity and was inhibited by azide. Plasma membrane uptake was of low capacity and unaffected by azide. The effect of oxalate on plasma membrane suggests that there is an outwardly directed Ca2+ pump in the myometrial cell membrane. Both mitochondria and plasma membrane may be important in the Cas2+ accumulation of relaxation in this muscle."}
{"id": "PMID:232492", "title": "Isozyme studies on the association of the herpes simplex virus type 1 thymidine kinase gene with human chromosomes in somatic cell hybrids.", "content": "To investigate chromosomal site(s) of integration of the herpes simplex virus type 1 (HSV-1) thymidine kinase (TK) gene in biochemically transformed [HeLa(BU25)/KOS 8-1] cells, these human cells which had been transformed by ultraviolet light-irradiated HSV-1 were fused with TK-negative mouse LM(TK-) cells, human-mouse somatic cell hybrid clones (LH81 clones 1-20) were isolated by HATG-ouabain selection and their chromosomes and isozymes were analyzed. Electrophoretic and serological analyses showed that all 20 clones expressed type-specific HSV-1 TK. Isozyme analyses on 29 gene-enzyme systems representing 22 human chromosomes revealed that all of the HSV-1 TK-positive clones expressed human aminoacylase-1 (ACY-1) and esterase D (ESD), which have been mapped to human chromosomes 3 and 13, respectively. Other human isozymes were detected in only one to four clones or in none of the clones. Chromosome analyses showed that: (1) the hybrid clones retained only a few human chromosomes; (2) a marker chromosome, designated M7, consisting of a chromosome 17 translocated to the short arm of chromosome 3, occurred in 36 out of the 41 metaphases examined of LH81-4 clones 1 to 4 and in 31 out of the 33 metaphases examined of LH81-12 clone 10; (3) a modified M7 chromosome, (M7/m), in which the distal 2/3 of the long arm of M7 was translocated to a small acrocentric mouse chromosome, was the only human chromosome found in metaphases of LH81-13 clone 17; and (4) an intact human chromosome 13 was not present in LH81-12 clone 10 or LH81-13 clone 17 cells. Counterselection with BrdUrd resulted in the isolation of subclones lacking HSV-1 TK, human ACY-1 and ESD, and the human marker M7 chromosomes. The experiments indicate that the HSV-1 TK gene is probably associated in HeLa (BU25)/KOS 8-1 cells with marker chromosome M7, but the possibility is not excluded that the segment of human chromosome 13 which codes for ESD is involved.", "contents": "Isozyme studies on the association of the herpes simplex virus type 1 thymidine kinase gene with human chromosomes in somatic cell hybrids. To investigate chromosomal site(s) of integration of the herpes simplex virus type 1 (HSV-1) thymidine kinase (TK) gene in biochemically transformed [HeLa(BU25)/KOS 8-1] cells, these human cells which had been transformed by ultraviolet light-irradiated HSV-1 were fused with TK-negative mouse LM(TK-) cells, human-mouse somatic cell hybrid clones (LH81 clones 1-20) were isolated by HATG-ouabain selection and their chromosomes and isozymes were analyzed. Electrophoretic and serological analyses showed that all 20 clones expressed type-specific HSV-1 TK. Isozyme analyses on 29 gene-enzyme systems representing 22 human chromosomes revealed that all of the HSV-1 TK-positive clones expressed human aminoacylase-1 (ACY-1) and esterase D (ESD), which have been mapped to human chromosomes 3 and 13, respectively. Other human isozymes were detected in only one to four clones or in none of the clones. Chromosome analyses showed that: (1) the hybrid clones retained only a few human chromosomes; (2) a marker chromosome, designated M7, consisting of a chromosome 17 translocated to the short arm of chromosome 3, occurred in 36 out of the 41 metaphases examined of LH81-4 clones 1 to 4 and in 31 out of the 33 metaphases examined of LH81-12 clone 10; (3) a modified M7 chromosome, (M7/m), in which the distal 2/3 of the long arm of M7 was translocated to a small acrocentric mouse chromosome, was the only human chromosome found in metaphases of LH81-13 clone 17; and (4) an intact human chromosome 13 was not present in LH81-12 clone 10 or LH81-13 clone 17 cells. Counterselection with BrdUrd resulted in the isolation of subclones lacking HSV-1 TK, human ACY-1 and ESD, and the human marker M7 chromosomes. The experiments indicate that the HSV-1 TK gene is probably associated in HeLa (BU25)/KOS 8-1 cells with marker chromosome M7, but the possibility is not excluded that the segment of human chromosome 13 which codes for ESD is involved."}
{"id": "PMID:232493", "title": "Luteinizing hormone-releasing factor-like immunoreactivity in islet cells and insulomas of the human pancreas.", "content": "Luteinizing hormone-releasing factor (LRF)-like immunoreactivity was demonstrated by a three-layer immunoperoxidase method in the islet cells of human pancreas and in the neoplastic cells of insulomas. Adenocarcinomas originating in the exocrine pancreas were LRF-negative. The results demonstrate another hypothalamic peptide-like material in the gastrointestinal tract, the biological role of which remains to be clarified.", "contents": "Luteinizing hormone-releasing factor-like immunoreactivity in islet cells and insulomas of the human pancreas. Luteinizing hormone-releasing factor (LRF)-like immunoreactivity was demonstrated by a three-layer immunoperoxidase method in the islet cells of human pancreas and in the neoplastic cells of insulomas. Adenocarcinomas originating in the exocrine pancreas were LRF-negative. The results demonstrate another hypothalamic peptide-like material in the gastrointestinal tract, the biological role of which remains to be clarified."}
{"id": "PMID:232489", "title": "Mechanism of angiotensin I converting enzyme inhibition by SQ20,881 (less than Glu-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro) in vivo. Further evidence for extrapulmonary conversion.", "content": "The mechanism by which the angiotensin I (AI) converting enzyme inhibitor SQ20,881 (less than Glu-Trp-Pro-Arg-Pro-Glu-Ile-Pro-Pro) blocks the pressor response to exogenous AI was studied in vivo in the intact anesthetized dog. When administered as a single dose 250 times that of injected AI (250 nmoles/kg) into either the pulmonary or systemic circulation, SQ20,881 produced inhibition of pulmonary conversion of exogenous AI to AII that lasted for more than 6 hours as judged by the absence of immunoreactive or labeled AII in the pulmonary venous effluent. In contrast, the pressor response to exogenous AI began to reappear within 1 hour of SQ20,881 administration. Six hours following SQ20,881, the pressor response to AI had nearly returned to normal, still in the absence of demonstrable intrapulmonary conversion and without release of detectable amounts of AII into the pulmonary venous effluent. These experiments demonstrated that AI has a pressor effect in the presence of SQ20,881 that is independent of pulmonary conversion. Studies with (Des-Asp) AII and (Des-Asp, Arg) AII showed that the delayed pressor response to AI following SQ20,881 administration could not be accounted for by circulating peptide metabolites of AI or AII. A competitive inhibitor of AII, (D-Asp, Ile) AII completely blocked the returning pressor response, suggesting that extrapulmonary generation of AII was responsible. The data strongly suggest that the systemic vascular bed taken as a whole contains large amounts of AI converting enzyme that is capable of rapid generation of AII without releasing the peptide into circulation. The extrapulmonary enzyme is more resistant to long-lasting blockade by SQ20,881 than pulmonary converting enzyme. The physiological role of extrapulmonary conversion systemic and local circulatory homeotasis remains to be assessed.", "contents": "Mechanism of angiotensin I converting enzyme inhibition by SQ20,881 (less than Glu-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro) in vivo. Further evidence for extrapulmonary conversion. The mechanism by which the angiotensin I (AI) converting enzyme inhibitor SQ20,881 (less than Glu-Trp-Pro-Arg-Pro-Glu-Ile-Pro-Pro) blocks the pressor response to exogenous AI was studied in vivo in the intact anesthetized dog. When administered as a single dose 250 times that of injected AI (250 nmoles/kg) into either the pulmonary or systemic circulation, SQ20,881 produced inhibition of pulmonary conversion of exogenous AI to AII that lasted for more than 6 hours as judged by the absence of immunoreactive or labeled AII in the pulmonary venous effluent. In contrast, the pressor response to exogenous AI began to reappear within 1 hour of SQ20,881 administration. Six hours following SQ20,881, the pressor response to AI had nearly returned to normal, still in the absence of demonstrable intrapulmonary conversion and without release of detectable amounts of AII into the pulmonary venous effluent. These experiments demonstrated that AI has a pressor effect in the presence of SQ20,881 that is independent of pulmonary conversion. Studies with (Des-Asp) AII and (Des-Asp, Arg) AII showed that the delayed pressor response to AI following SQ20,881 administration could not be accounted for by circulating peptide metabolites of AI or AII. A competitive inhibitor of AII, (D-Asp, Ile) AII completely blocked the returning pressor response, suggesting that extrapulmonary generation of AII was responsible. The data strongly suggest that the systemic vascular bed taken as a whole contains large amounts of AI converting enzyme that is capable of rapid generation of AII without releasing the peptide into circulation. The extrapulmonary enzyme is more resistant to long-lasting blockade by SQ20,881 than pulmonary converting enzyme. The physiological role of extrapulmonary conversion systemic and local circulatory homeotasis remains to be assessed."}
{"id": "PMID:232494", "title": "Bioactivities and the effect of dilution on various milk-borne murine mammary tumor viruses.", "content": "Infectivity titrations of milk-borne murine mammary tumor virus (MuMTV) from different sources or prepared in different ways or stored for periods of time have been compared. Titration curves were in general reproducible for MuMTVs of different sources or handled in different ways and for different methods of measurement, such as hyperplastic alveolar nodule (HAN) development, tumor development, or MuMTV antigen secretion in third-lactation milk, The curves had characteristic shapes with a low incidence of infection at low dilutions of milk, high incidences at intermediate dilutions, and low incidences at high dilutions. Infectivity incidences were unaffected by dilution over the range 10(-2) to 10(-5). The curves did not change appreciably with time of storage of milk at liquid N2 temperature for periods up to 3 years. Rate zonal fractionation of RIII milk gave zones with bioactivities which were not proportional to B-particle content. Upon dilution, the bioactivity of Zone 3, rich in B particles, and Zone 5, poor in B particles, increased, while the bioactivity of all the other zones usually decreased with dilution. The low incidence of infection at low dilutions may have been due, in part, to an immune response of the inoculated mouse. Administration of inactivated virions 4 h prior to or with MuMTV inoculations gave some evidence in support of this hypothesis but the complexity of the bioassay system for MuMTV lends uncertainty to interpretation of results.", "contents": "Bioactivities and the effect of dilution on various milk-borne murine mammary tumor viruses. Infectivity titrations of milk-borne murine mammary tumor virus (MuMTV) from different sources or prepared in different ways or stored for periods of time have been compared. Titration curves were in general reproducible for MuMTVs of different sources or handled in different ways and for different methods of measurement, such as hyperplastic alveolar nodule (HAN) development, tumor development, or MuMTV antigen secretion in third-lactation milk, The curves had characteristic shapes with a low incidence of infection at low dilutions of milk, high incidences at intermediate dilutions, and low incidences at high dilutions. Infectivity incidences were unaffected by dilution over the range 10(-2) to 10(-5). The curves did not change appreciably with time of storage of milk at liquid N2 temperature for periods up to 3 years. Rate zonal fractionation of RIII milk gave zones with bioactivities which were not proportional to B-particle content. Upon dilution, the bioactivity of Zone 3, rich in B particles, and Zone 5, poor in B particles, increased, while the bioactivity of all the other zones usually decreased with dilution. The low incidence of infection at low dilutions may have been due, in part, to an immune response of the inoculated mouse. Administration of inactivated virions 4 h prior to or with MuMTV inoculations gave some evidence in support of this hypothesis but the complexity of the bioassay system for MuMTV lends uncertainty to interpretation of results."}
{"id": "PMID:232490", "title": "Converting enzyme inhibition with an orally active compound in hypertensive man.", "content": "The short-term cardiovascular and endocrine effects of an orally active angiotensin converting enzyme inhibitor, SQ14,225, were evaluated in 17 subjects with drug-resistant hypertension (10 with essential and seven with renovascular hypertension). On normal dietary sodium, SQ14,225 (after 3 days at average dose of 664 mg/day) reduced mean arterial pressure (MAP) significantly (from 141 +/- 4 to 122 +/- 4 mm Hg, (SE), p less than 0.001). However, only eight of the patients achieved blood pressures within the normotensive range. Of eight patients with residual hypertension, seven exhibited further decreases in MAP (from 132 +/- 4 to 108 +/- 6 mm Hg (SE), p less than 0.001) when dietary sodium was reduced to 10 mEq/day. No rebound hypertension was noted when treatment was temporarily discontinued for 3 days in 11 patients. The reductions in blood pressure were not associated with either orthostatic hypotension or interference with baroreceptor reflexes. The values of supine plasma renin activity (PRA) were not always predictive of blood pressure responsiveness to the drug. With treatment, plasma aldosterone concentrations (PAC) decreased modestly (values from 40 +/- 9 to 22 +/- 3 ng/dl (SE), p less than 0.05). The plasma concentrations of cortisol, norepinephrine and serum potassium were left unchanged during the period of studies. The present study has not defined the exact mechanism by which SQ14,225 lowered blood pressure. Nevertheless, it indicates that this agent may be a practical therapeutic adjunct in the treatment of certain subsets of the human hypertensive population. The lack of serious interference with cardioscular and humoral homeostasis adds to its attractiveness as a therapeutic agent.", "contents": "Converting enzyme inhibition with an orally active compound in hypertensive man. The short-term cardiovascular and endocrine effects of an orally active angiotensin converting enzyme inhibitor, SQ14,225, were evaluated in 17 subjects with drug-resistant hypertension (10 with essential and seven with renovascular hypertension). On normal dietary sodium, SQ14,225 (after 3 days at average dose of 664 mg/day) reduced mean arterial pressure (MAP) significantly (from 141 +/- 4 to 122 +/- 4 mm Hg, (SE), p less than 0.001). However, only eight of the patients achieved blood pressures within the normotensive range. Of eight patients with residual hypertension, seven exhibited further decreases in MAP (from 132 +/- 4 to 108 +/- 6 mm Hg (SE), p less than 0.001) when dietary sodium was reduced to 10 mEq/day. No rebound hypertension was noted when treatment was temporarily discontinued for 3 days in 11 patients. The reductions in blood pressure were not associated with either orthostatic hypotension or interference with baroreceptor reflexes. The values of supine plasma renin activity (PRA) were not always predictive of blood pressure responsiveness to the drug. With treatment, plasma aldosterone concentrations (PAC) decreased modestly (values from 40 +/- 9 to 22 +/- 3 ng/dl (SE), p less than 0.05). The plasma concentrations of cortisol, norepinephrine and serum potassium were left unchanged during the period of studies. The present study has not defined the exact mechanism by which SQ14,225 lowered blood pressure. Nevertheless, it indicates that this agent may be a practical therapeutic adjunct in the treatment of certain subsets of the human hypertensive population. The lack of serious interference with cardioscular and humoral homeostasis adds to its attractiveness as a therapeutic agent."}
{"id": "PMID:232495", "title": "Membrane dynamic alteration associated with the tumorigenicity of polyoma-transformed and revertant hamster cells.", "content": "Steady state fluorescence polarization studies were carried out on membranes of polyoma-virus-transformed, revertants, re-revertants, and normal golden hamster cells. Four clones of revertant cells which exhibit different levels of reversion were isolated. The degree of reversion in these revertant clones was characterized in vitro by their contact inhibition behavior and in vivo by their tumorigenicity to hamsters. A good correlation between these two criteria was observed. Re-revertant cells were obtained from that revertant clone which exhibited the highest degree of reversion (similar to normal cells) and which could still produce tumors in hamsters. Re-revertants resembled the polyomavirus-transformed cells in both contact inhibition and tumorigenicity. Fluorescence polarization values of 1.6-diphenyl-1,3,5-hexatriene-labelled cells correlated well with cell tumorigenicity: normal and revertant cells which were not malignant exhibited distinctly lower fluorescence polarization values than those of the tumorigenic transformed and re-revertant cells. Intermediary revertant clones exhibited fluorescence polarization values in between those of normal and transformed cells, yet indistinguishable within experimental uncertainty.", "contents": "Membrane dynamic alteration associated with the tumorigenicity of polyoma-transformed and revertant hamster cells. Steady state fluorescence polarization studies were carried out on membranes of polyoma-virus-transformed, revertants, re-revertants, and normal golden hamster cells. Four clones of revertant cells which exhibit different levels of reversion were isolated. The degree of reversion in these revertant clones was characterized in vitro by their contact inhibition behavior and in vivo by their tumorigenicity to hamsters. A good correlation between these two criteria was observed. Re-revertant cells were obtained from that revertant clone which exhibited the highest degree of reversion (similar to normal cells) and which could still produce tumors in hamsters. Re-revertants resembled the polyomavirus-transformed cells in both contact inhibition and tumorigenicity. Fluorescence polarization values of 1.6-diphenyl-1,3,5-hexatriene-labelled cells correlated well with cell tumorigenicity: normal and revertant cells which were not malignant exhibited distinctly lower fluorescence polarization values than those of the tumorigenic transformed and re-revertant cells. Intermediary revertant clones exhibited fluorescence polarization values in between those of normal and transformed cells, yet indistinguishable within experimental uncertainty."}
{"id": "PMID:232496", "title": "Activation of mouse macrophages by pyran copolymer and role in augmentation of natural killer activity.", "content": "Inoculation of mice with pyran copolymer resulted in activation of natural killer (NK) cells as well as macrophages. Conditions optimal for the boosting of NK activity seemed to differ from those optimal for macrophage activation as assessed by cytostasis of tumor target cells. Peak levels of macrophage cytostatic reactivity were found at about 7 days after drug injection and were only achieved by the highest doses of pyran tested. Macrophage activation was consistently higher in the peritoneal cavity than in the spleen, regardless of route of administration, in contrast to the failure of i.v. pyran to induce high NK reactivity in peritoneal exudate cells. At 2-3 days after pyran treatment of older mice, NK augmentation reached peak levels, but only minimal macrophage activation was found. Despite these differences, macrophages played a role in regulating NK activity in pyran-treated mice. Functional macrophages appeared to be required for augmentation of NK activity by pyran, since boosting was impaired by prior in vivo inoculation of silica. Macrophages also appeared able to inhibit NK activity. In younger mice that exhibited high spontaneous levels of NK activity, pyran treatment produced a substantial reduction in NK activity to levels below those of untreated mice. This depression coincided with the time of peak levels of macrophage cytostasis. Furthermore, removal of adherent cells from the spleen cells of these pyran-treated mice resulted in levels of NK activity almost as high as those of untreated mice. The possibility that the depression of NK activity in young mice by pyran copolymer is due to suppressor cells is discussed.", "contents": "Activation of mouse macrophages by pyran copolymer and role in augmentation of natural killer activity. Inoculation of mice with pyran copolymer resulted in activation of natural killer (NK) cells as well as macrophages. Conditions optimal for the boosting of NK activity seemed to differ from those optimal for macrophage activation as assessed by cytostasis of tumor target cells. Peak levels of macrophage cytostatic reactivity were found at about 7 days after drug injection and were only achieved by the highest doses of pyran tested. Macrophage activation was consistently higher in the peritoneal cavity than in the spleen, regardless of route of administration, in contrast to the failure of i.v. pyran to induce high NK reactivity in peritoneal exudate cells. At 2-3 days after pyran treatment of older mice, NK augmentation reached peak levels, but only minimal macrophage activation was found. Despite these differences, macrophages played a role in regulating NK activity in pyran-treated mice. Functional macrophages appeared to be required for augmentation of NK activity by pyran, since boosting was impaired by prior in vivo inoculation of silica. Macrophages also appeared able to inhibit NK activity. In younger mice that exhibited high spontaneous levels of NK activity, pyran treatment produced a substantial reduction in NK activity to levels below those of untreated mice. This depression coincided with the time of peak levels of macrophage cytostasis. Furthermore, removal of adherent cells from the spleen cells of these pyran-treated mice resulted in levels of NK activity almost as high as those of untreated mice. The possibility that the depression of NK activity in young mice by pyran copolymer is due to suppressor cells is discussed."}
{"id": "PMID:232497", "title": "Effects of 645 MeV and 9.2 GeV protons on Artemia eggs.", "content": "Developmental capacities of Artemia eggs have been studied after exposure to 645 MeV or 9.2 GeV protons. Effects of proton irradiation were studied in comparison with 60Co gamma ray irradiation, endpoints being emergence, hatching and 4-5 day old live nauplii percentages. Effectiveness of 645 MeV protons is greater than that of 9.2 GeV protons. R.b.e. values calculated for nauplius survival is 2.3 for 645 MeV protons and 1.5 for 9.2 GeV protons. These results can be taken into account in radiation hazard estimation during space flights.", "contents": "Effects of 645 MeV and 9.2 GeV protons on Artemia eggs. Developmental capacities of Artemia eggs have been studied after exposure to 645 MeV or 9.2 GeV protons. Effects of proton irradiation were studied in comparison with 60Co gamma ray irradiation, endpoints being emergence, hatching and 4-5 day old live nauplii percentages. Effectiveness of 645 MeV protons is greater than that of 9.2 GeV protons. R.b.e. values calculated for nauplius survival is 2.3 for 645 MeV protons and 1.5 for 9.2 GeV protons. These results can be taken into account in radiation hazard estimation during space flights."}
{"id": "PMID:232502", "title": "Routine reversed-phase high-performance liquid chromatographic measurement of urinary vanillylmandelic acid in patients with neural crest tumors.", "content": "A rapid and simple reversed-phase high-performance liquid chromatographic procedure for the determination of vanillylmandelic acid (VMA) is described. This method was applied in the determination of the VMA content in urine from normal subjects and patients with neural crest lesions. Sample preparation is minimal and the analysis is short (20 min) and reproducible. The sensitivity of the UV detection is in the ng range. By this technique, fourteen adult control subjects were found to excrete a mean of 2.86 microgram VMA per mg creatinine, whereas twelve patients with pheochromocytoma excreted a mean of 15.7 microgram VMA per mg creatinine.", "contents": "Routine reversed-phase high-performance liquid chromatographic measurement of urinary vanillylmandelic acid in patients with neural crest tumors. A rapid and simple reversed-phase high-performance liquid chromatographic procedure for the determination of vanillylmandelic acid (VMA) is described. This method was applied in the determination of the VMA content in urine from normal subjects and patients with neural crest lesions. Sample preparation is minimal and the analysis is short (20 min) and reproducible. The sensitivity of the UV detection is in the ng range. By this technique, fourteen adult control subjects were found to excrete a mean of 2.86 microgram VMA per mg creatinine, whereas twelve patients with pheochromocytoma excreted a mean of 15.7 microgram VMA per mg creatinine."}
{"id": "PMID:232503", "title": "DEAE-silica gel and DEAE-controlled porous glass as ion exchangers for isolation of glycolipids.", "content": "DEAE-silica gel and DEAE-controlled porous glass have been used for the quantitative isolation of gangliosides and neutral glycosphingolipids from animal tissues and cells. A direct comparative study between DEAE-silica gel, DEAE-controlled porous glass and DEAE-Sephadex was made; the results indicated that DEAE-silica gel is preferable to the other two ion exchangers. DEAE-silica gel has also been found to be suitable for the fractionation of ganglioside mixtures.", "contents": "DEAE-silica gel and DEAE-controlled porous glass as ion exchangers for isolation of glycolipids. DEAE-silica gel and DEAE-controlled porous glass have been used for the quantitative isolation of gangliosides and neutral glycosphingolipids from animal tissues and cells. A direct comparative study between DEAE-silica gel, DEAE-controlled porous glass and DEAE-Sephadex was made; the results indicated that DEAE-silica gel is preferable to the other two ion exchangers. DEAE-silica gel has also been found to be suitable for the fractionation of ganglioside mixtures."}
{"id": "PMID:232504", "title": "Detection of immunoglobulin M antibodies to hepatitis A virus by enzyme-linked immunosorbent assay.", "content": "An enzyme-linked immunosorbent assay for the detection of immunoglobulin M (IgM) antibodies to hepatitis A virus is described. The test uses the principle of binding of IgM antibodies to anti-IgM-coated microtiter plates to determine whether the IgM antibodies attached have specificities for hepatitis A virus. In three patients with hepatitis type A followed up to 12 months, IgM antibodies to hepatitis A virus could be demonstrated from the onset of illness and during the following 2 to 3 months. When acute-phase sera from 48 patients with acute hepatitis were tested, IgM antibodies to hepatitis A virus could only be demonstrated in 18 patients previously classified as type A, whereas 30 patients with type B and non-A non-B hepatitis were negative. IgM antibodies to hepatitis A virus could not be demonstrated in 108 normal sera nor in 55 sera containing rheumatoid factor. These results indicate that the enzyme-linked immunosorbent assay for IgM antibodies to hepatitis A virus is useful in the serodiagnosis of acute hepatitis type A on a single serum sample taken during the acute phase of illness.", "contents": "Detection of immunoglobulin M antibodies to hepatitis A virus by enzyme-linked immunosorbent assay. An enzyme-linked immunosorbent assay for the detection of immunoglobulin M (IgM) antibodies to hepatitis A virus is described. The test uses the principle of binding of IgM antibodies to anti-IgM-coated microtiter plates to determine whether the IgM antibodies attached have specificities for hepatitis A virus. In three patients with hepatitis type A followed up to 12 months, IgM antibodies to hepatitis A virus could be demonstrated from the onset of illness and during the following 2 to 3 months. When acute-phase sera from 48 patients with acute hepatitis were tested, IgM antibodies to hepatitis A virus could only be demonstrated in 18 patients previously classified as type A, whereas 30 patients with type B and non-A non-B hepatitis were negative. IgM antibodies to hepatitis A virus could not be demonstrated in 108 normal sera nor in 55 sera containing rheumatoid factor. These results indicate that the enzyme-linked immunosorbent assay for IgM antibodies to hepatitis A virus is useful in the serodiagnosis of acute hepatitis type A on a single serum sample taken during the acute phase of illness."}
{"id": "PMID:232505", "title": "Enzyme-linked immunosorbent assay for serology of infectious bovine rhinotracheitis virus infections.", "content": "An enzyme-linked immunosorbent assay was developed to detect antibodies to infectious bovine rhinotracheitis virus in bovine sera. The test used viral antigen purified in a sucrose density gradient, and the antibody titers detected were up to 100 times higher than those seen in the serum neutralization test. When 250 sera were tested by those two tests, 146 were positive and 49 were negative in both tests. Only 1 serum was negative in the immunoassay test and positive in the neutralization test. However, 54 sera negative in the neutralization test were positive in the immunoassay test. These positive results appear to be in agreement with the increased sensitivity of the enzyme immunoassay.", "contents": "Enzyme-linked immunosorbent assay for serology of infectious bovine rhinotracheitis virus infections. An enzyme-linked immunosorbent assay was developed to detect antibodies to infectious bovine rhinotracheitis virus in bovine sera. The test used viral antigen purified in a sucrose density gradient, and the antibody titers detected were up to 100 times higher than those seen in the serum neutralization test. When 250 sera were tested by those two tests, 146 were positive and 49 were negative in both tests. Only 1 serum was negative in the immunoassay test and positive in the neutralization test. However, 54 sera negative in the neutralization test were positive in the immunoassay test. These positive results appear to be in agreement with the increased sensitivity of the enzyme immunoassay."}
{"id": "PMID:232506", "title": "Analysis of nonspecific reactions in enzyme-linked immunosorbent assay testing for human rotavirus.", "content": "Solid-phase enzyme immunoassays can be utilized to detect antigens directly in clinical specimens. However, a small number of stools which we tested for human rotavirus by enzyme-linked immunosorbent assay (ELISA) were found to have nonspecific activity in the absence of rotaviral antigen. Similar nonspecific activity was found in eight of eight sera which contained rheumatoid factor. This nonspecific activity was markedly reduced by pretreatment of the specimens with reducing agents, normal goat serum, and anti-human immunoglobulin M (IgM). Thus, it is likely that these specimens contain an IgM antibody capable of reacting nonspecifically with the other components of the assay. Although pretreatment with the mild reducing agent N-acetylcysteine markedly reduced this nonspecific activity, such treatment did not reduce the specific ELISA activity due to rotavirus. Other treatments did produce a reduction in specific activity. Thus pretreatment with N-acetylcysteine offers a practical means to increase the specificity of ELISA systems without reducing their sensitivity.", "contents": "Analysis of nonspecific reactions in enzyme-linked immunosorbent assay testing for human rotavirus. Solid-phase enzyme immunoassays can be utilized to detect antigens directly in clinical specimens. However, a small number of stools which we tested for human rotavirus by enzyme-linked immunosorbent assay (ELISA) were found to have nonspecific activity in the absence of rotaviral antigen. Similar nonspecific activity was found in eight of eight sera which contained rheumatoid factor. This nonspecific activity was markedly reduced by pretreatment of the specimens with reducing agents, normal goat serum, and anti-human immunoglobulin M (IgM). Thus, it is likely that these specimens contain an IgM antibody capable of reacting nonspecifically with the other components of the assay. Although pretreatment with the mild reducing agent N-acetylcysteine markedly reduced this nonspecific activity, such treatment did not reduce the specific ELISA activity due to rotavirus. Other treatments did produce a reduction in specific activity. Thus pretreatment with N-acetylcysteine offers a practical means to increase the specificity of ELISA systems without reducing their sensitivity."}
{"id": "PMID:232507", "title": "Enzyme immunoassay for detection of antibody to Epstein-Barr virus-specific early antigen.", "content": "Antibody to Epstein-Barr virus-induced early antigen could be measured in sera using enzyme-linked antibody. The sensitivity of this assay was comparable to that of the indirect immunofluorescent technique. Measurement of early antigen was accomplished on a producer cell line which was specifically treated to block late gene expression. It is now possible to measure Epstein-Barr virus-induced early antigen and viral capsid antigen antibodies by using the same cell line.", "contents": "Enzyme immunoassay for detection of antibody to Epstein-Barr virus-specific early antigen. Antibody to Epstein-Barr virus-induced early antigen could be measured in sera using enzyme-linked antibody. The sensitivity of this assay was comparable to that of the indirect immunofluorescent technique. Measurement of early antigen was accomplished on a producer cell line which was specifically treated to block late gene expression. It is now possible to measure Epstein-Barr virus-induced early antigen and viral capsid antigen antibodies by using the same cell line."}
{"id": "PMID:232511", "title": "[Influence of active vitamine D3 on bones (author's transl)].", "content": "Influence of 1 alpha-OH-D3, an active vitamine D supplement, on bone cells was studied, histologically and electro-microscopically observing the vitamine D objective bone cell after treatment with the drug in a dose of 50 microgram/kg/day. Light-microscopic findings revealed that osteogenesis gradually became dominant after transient osteoporosis, leading to a disproportional state of the bone remodelling. In electromicroscopy, no morphological changes were observed, though the number of osteoclasts increased five days after treatment. Hypofunctional findings, however, appeared seven and ten days after treatment. On the other hand, findings of distinguishable osteogenesis, e.g. well-developed golgi complex (G), endoplasmic reticulum (ER), mitochondria (M), were observed in the osteoblast and osteocyte, defining the strong influence of vitamine D in a large dose on the osteoblast-osteocyte system. Especially, the osteoblast seemed to be influenced earlier and to a greater degree. We concluded that 1 alpha-OH-D3 in doses of 0.02 and 0.08 microgram/kg/day hardly caused any morphological changes in the bone cell in our experiment.", "contents": "[Influence of active vitamine D3 on bones (author's transl)]. Influence of 1 alpha-OH-D3, an active vitamine D supplement, on bone cells was studied, histologically and electro-microscopically observing the vitamine D objective bone cell after treatment with the drug in a dose of 50 microgram/kg/day. Light-microscopic findings revealed that osteogenesis gradually became dominant after transient osteoporosis, leading to a disproportional state of the bone remodelling. In electromicroscopy, no morphological changes were observed, though the number of osteoclasts increased five days after treatment. Hypofunctional findings, however, appeared seven and ten days after treatment. On the other hand, findings of distinguishable osteogenesis, e.g. well-developed golgi complex (G), endoplasmic reticulum (ER), mitochondria (M), were observed in the osteoblast and osteocyte, defining the strong influence of vitamine D in a large dose on the osteoblast-osteocyte system. Especially, the osteoblast seemed to be influenced earlier and to a greater degree. We concluded that 1 alpha-OH-D3 in doses of 0.02 and 0.08 microgram/kg/day hardly caused any morphological changes in the bone cell in our experiment."}
{"id": "PMID:232517", "title": "Detection by proton nuclear magnetic resonance of elevated lactate concentration in serums from patients with malignant tumors.", "content": "Proton nuclear magnetic resonance (1H-NMR) spectra of the serum specimens from patients with malignant tumors were compared with those from presumably healthy persons. We found that 87% of serum specimens from the patients yielded a common proton signal, which was ascribed to the methyl protons of lactic acid; whereas only 9% of serum specimens from the healthy persons tested gave this signal. On the basis of these results we concluded that the lactate level in the serum can be used as a criterion for the diagnosis of cancer in humans and that the determination of lactate concentration in the serum is easily performed by means of 1H-NMR.", "contents": "Detection by proton nuclear magnetic resonance of elevated lactate concentration in serums from patients with malignant tumors. Proton nuclear magnetic resonance (1H-NMR) spectra of the serum specimens from patients with malignant tumors were compared with those from presumably healthy persons. We found that 87% of serum specimens from the patients yielded a common proton signal, which was ascribed to the methyl protons of lactic acid; whereas only 9% of serum specimens from the healthy persons tested gave this signal. On the basis of these results we concluded that the lactate level in the serum can be used as a criterion for the diagnosis of cancer in humans and that the determination of lactate concentration in the serum is easily performed by means of 1H-NMR."}
{"id": "PMID:232519", "title": "Preoperative estimation of operative risk in liver surgery, with special reference to functional reserve of the remnant liver following major hepatic resection.", "content": "Hepatic functional reserve was evaluated in 76 patients with known liver, biliary tract or pancreas diseases using kinetic analysis of removal of indocyanine green (ICG) with special reference to maximal removal rate (Rmax). In surgery other than hepatectomy, if ICG Rmax is below 0.4 mg/kg/min the operative risk should be considered high. In hepatic surgery, even if ICG Rmax is above 0.4 mg/kg/min the operative risk was high and it should be required to be above 1.0 mg/kg/min for extended lobectomy or hepatectomy. Furthermore, prior to hepatectomy the functional reserve of the remnant liver was estimated from an effective liver volume rate, calculated from the rate of uptake of radioisotope as measured by on-line computer system, and ICG Rmax. The functional reserve of the remnant liver was compared with the operative results, such as morbidity or mortality for each patient. When ICG Rmax of the remnant liver was below 0.4 mg/kg/min the prognosis was poor in hepatic surgery, because of there were three postoperative death and seven complications such as ascites or liver failure in the ten cases. On the other hand, when above 0.4 mg/kg/min, the prognosis was good without any postoperative death or complications in the twelve cases of hepatic surgery, as the completely same results for general surgery, in which it is as well when ICG Rmax of whole liver is above 0.4 mg/kg/min.", "contents": "Preoperative estimation of operative risk in liver surgery, with special reference to functional reserve of the remnant liver following major hepatic resection. Hepatic functional reserve was evaluated in 76 patients with known liver, biliary tract or pancreas diseases using kinetic analysis of removal of indocyanine green (ICG) with special reference to maximal removal rate (Rmax). In surgery other than hepatectomy, if ICG Rmax is below 0.4 mg/kg/min the operative risk should be considered high. In hepatic surgery, even if ICG Rmax is above 0.4 mg/kg/min the operative risk was high and it should be required to be above 1.0 mg/kg/min for extended lobectomy or hepatectomy. Furthermore, prior to hepatectomy the functional reserve of the remnant liver was estimated from an effective liver volume rate, calculated from the rate of uptake of radioisotope as measured by on-line computer system, and ICG Rmax. The functional reserve of the remnant liver was compared with the operative results, such as morbidity or mortality for each patient. When ICG Rmax of the remnant liver was below 0.4 mg/kg/min the prognosis was poor in hepatic surgery, because of there were three postoperative death and seven complications such as ascites or liver failure in the ten cases. On the other hand, when above 0.4 mg/kg/min, the prognosis was good without any postoperative death or complications in the twelve cases of hepatic surgery, as the completely same results for general surgery, in which it is as well when ICG Rmax of whole liver is above 0.4 mg/kg/min."}
{"id": "PMID:232520", "title": "Isolation and immunological characterization of an iron-regulated, transformation-sensitive cell surface protein of normal rat kidney cells.", "content": "We have analyzed the surfacr proteins of cultured normal rat kidney (NRK) cells and virus-transformed NRK cells subjected to iron deprivation. Such a treatment specifically induces two transformation-sensitive plasma membrane-associated glycoproteins with a subunit molecular weight of 160,000 (160 K) and 130,000 (130 K) daltons in NRK cells. In these cells the 160 K glycoprotein is readily available to lactoperoxidase-mediated iodination, and the 130 K is apparently inaccessible to iodination. Major differences were revealed when iodinated membrane proteins of normal and virus-transformed cells subjected to iron deprivation were compared. In Kirsten sarcoma virus-transformed NRK cells the 160 K glycoprotein was weakly labeled. In two clones of simian virus 40-transformed NRK cells the 160 K glycoprotein was weakly labeled or not at all. The 130 K glycoprotein was inaccessible to iodination in all virus-transformed cell lines. The 160 K and 130 K glycoproteins were isolated from plasma membranes of NRK cells using preparative SDS gel electrophoresis. Antibodies generated against these glycoproteins stained the external surfaces of NRK cells and induced antigen redistribution. Evidence presented suggests that 160 K and 130 K are plasma membrane-associated procollagen molecules. A possible interaction of these proteins with transferrin is also described. The data suggest that these proteins may have an important role in the sequence of events leading to transformation.", "contents": "Isolation and immunological characterization of an iron-regulated, transformation-sensitive cell surface protein of normal rat kidney cells. We have analyzed the surfacr proteins of cultured normal rat kidney (NRK) cells and virus-transformed NRK cells subjected to iron deprivation. Such a treatment specifically induces two transformation-sensitive plasma membrane-associated glycoproteins with a subunit molecular weight of 160,000 (160 K) and 130,000 (130 K) daltons in NRK cells. In these cells the 160 K glycoprotein is readily available to lactoperoxidase-mediated iodination, and the 130 K is apparently inaccessible to iodination. Major differences were revealed when iodinated membrane proteins of normal and virus-transformed cells subjected to iron deprivation were compared. In Kirsten sarcoma virus-transformed NRK cells the 160 K glycoprotein was weakly labeled. In two clones of simian virus 40-transformed NRK cells the 160 K glycoprotein was weakly labeled or not at all. The 130 K glycoprotein was inaccessible to iodination in all virus-transformed cell lines. The 160 K and 130 K glycoproteins were isolated from plasma membranes of NRK cells using preparative SDS gel electrophoresis. Antibodies generated against these glycoproteins stained the external surfaces of NRK cells and induced antigen redistribution. Evidence presented suggests that 160 K and 130 K are plasma membrane-associated procollagen molecules. A possible interaction of these proteins with transferrin is also described. The data suggest that these proteins may have an important role in the sequence of events leading to transformation."}
{"id": "PMID:232521", "title": "Fibronectin and proteoglycans as determinants of cell-substratum adhesion.", "content": "When normal or SV40-transformed Balb/c 3T3 cells are treated with the Ca++-specific chelator EGTA, they round up and pull away from their footpad adhesion sites to the serum-coated tissue culture substrate, as shown by scanning electron microscope studies. Elastic membranous retraction fibers break upon culture agitation, leaving adhesion sites as substrate-attached material (SAM) (Cells leave \"footprints\" of substrate adhesion sites during movement by a very similar process.) SAM contains 1-2% of the cell's total protein and phospholipid content and 5-10% of its glucosamine-radiolabeled polysaccharide, most of which is glycosaminoglycan (GAG). By one- and two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis, there is considerable enrichment in SAM for specific GAGs; for the glycoprotein fibronectin; and for the cytoskeletal proteins actin, myosin, and the subunit protein of the 10 nm-diameter filaments. Fibrillar fibronectin of cellular origin and substratum-bound fibronectin of serum origin (cold-insoluble globulin, CIg) have been visualized by immunofluorescence microscopy. The GAG composition in SAM has been examined under different cellular growth and attachment conditions. Heparan sulfate content correlates with glycopeptide content (derived from glycoprotein). Newly attaching cells deposit SAM with principally heparan sulfate and fibronectin and little of the other GAGs. Hyaluronate and chrondroitin proteoglycans are coordinately deposited in SAM as cells begin spreading and movement over the substrate. Cells attaching to serum-coated or CIg-coated substrates deposited SAM with identical compositions. The proteoglycan nature of the GAGs in SAM has been examined, as well as the ability of proteoglycans to form two classes of reversibly dissociable \"supramolecular complexes\" - one class with heparan sulfate and glycopeptide-containing material and the second with hyaluronate-chondroitin complexes. Enzymatic digestion of \"intact\" SAM with trypsin or testicular hyaluronidase indicates that (1) only a small portion of long-term radiolabeled fibronectin and cyto-skeletal protein is bound to the substrate via hyaluronate or chondroitin classes of GAG; (2) most of the fibronectin, cytoskeletal protein and heparan sulfate coordinately resist solubilization; and (3) newly synthesized fibronectin, which is metabolically labile in SAM, is linked to SAM by hyaluronate- and/or chondroitin-dependent binding. All of our studies indicate that heparan sulfate is a direct mediator of adhesion of cells to the substrate, possibly by binding to both cell-surface fibronectin and substrate-bound CIg in the serum coating; hyaluronate-chondroitin complexes in SAM appear to be most important in motility of cells by binding and labilizing fibronectin at the periphery of footpad adhesions, with subsequent cytoskeletal disorganization.", "contents": "Fibronectin and proteoglycans as determinants of cell-substratum adhesion. When normal or SV40-transformed Balb/c 3T3 cells are treated with the Ca++-specific chelator EGTA, they round up and pull away from their footpad adhesion sites to the serum-coated tissue culture substrate, as shown by scanning electron microscope studies. Elastic membranous retraction fibers break upon culture agitation, leaving adhesion sites as substrate-attached material (SAM) (Cells leave \"footprints\" of substrate adhesion sites during movement by a very similar process.) SAM contains 1-2% of the cell's total protein and phospholipid content and 5-10% of its glucosamine-radiolabeled polysaccharide, most of which is glycosaminoglycan (GAG). By one- and two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis, there is considerable enrichment in SAM for specific GAGs; for the glycoprotein fibronectin; and for the cytoskeletal proteins actin, myosin, and the subunit protein of the 10 nm-diameter filaments. Fibrillar fibronectin of cellular origin and substratum-bound fibronectin of serum origin (cold-insoluble globulin, CIg) have been visualized by immunofluorescence microscopy. The GAG composition in SAM has been examined under different cellular growth and attachment conditions. Heparan sulfate content correlates with glycopeptide content (derived from glycoprotein). Newly attaching cells deposit SAM with principally heparan sulfate and fibronectin and little of the other GAGs. Hyaluronate and chrondroitin proteoglycans are coordinately deposited in SAM as cells begin spreading and movement over the substrate. Cells attaching to serum-coated or CIg-coated substrates deposited SAM with identical compositions. The proteoglycan nature of the GAGs in SAM has been examined, as well as the ability of proteoglycans to form two classes of reversibly dissociable \"supramolecular complexes\" - one class with heparan sulfate and glycopeptide-containing material and the second with hyaluronate-chondroitin complexes. Enzymatic digestion of \"intact\" SAM with trypsin or testicular hyaluronidase indicates that (1) only a small portion of long-term radiolabeled fibronectin and cyto-skeletal protein is bound to the substrate via hyaluronate or chondroitin classes of GAG; (2) most of the fibronectin, cytoskeletal protein and heparan sulfate coordinately resist solubilization; and (3) newly synthesized fibronectin, which is metabolically labile in SAM, is linked to SAM by hyaluronate- and/or chondroitin-dependent binding. All of our studies indicate that heparan sulfate is a direct mediator of adhesion of cells to the substrate, possibly by binding to both cell-surface fibronectin and substrate-bound CIg in the serum coating; hyaluronate-chondroitin complexes in SAM appear to be most important in motility of cells by binding and labilizing fibronectin at the periphery of footpad adhesions, with subsequent cytoskeletal disorganization."}
{"id": "PMID:232522", "title": "Cholesterol levels and plasma membrane fluidity in 3T3 and SV101-3T3 cells.", "content": "Polyene antibiotics such as filipin selectively inhibit wheat germ agglutinin-induced agglutination of transformed and malignant cells compared to normal cells (Hatten ME, Burger MM: Biochemistry 18: 739, 1979). Since filipin binds specifically to cholesterol, we measured cholesterol levels in 3T3 cells and SV101-3T3 cells. SV101-3T3 cells contained 50-100% more cholesterol per cell than 3T3 cells. Both cell types were starved for cholesterol by growth in lipid-depleted medium plus 25-hydroxycholesterol. The cholesterol level of SV101-3T3 cells decreased by 30-50%, while the level in 3T3 cells remained constant. Filipin-stained SV101-3T3 cells revealed bright patches of filipin under fluorescence microscopy. These patches were absent in 3T3 cells and in SV101-3T3 and 3T3 cells starved for cholesterol. We selectively labeled plasma membranes of these cells with a spin label analog of phosphatidylcholine. The spin label indicated differences in plasma membrane fluidity that may be related to the different cholesterol levels in 3T3 and SV101-3T3 cells.", "contents": "Cholesterol levels and plasma membrane fluidity in 3T3 and SV101-3T3 cells. Polyene antibiotics such as filipin selectively inhibit wheat germ agglutinin-induced agglutination of transformed and malignant cells compared to normal cells (Hatten ME, Burger MM: Biochemistry 18: 739, 1979). Since filipin binds specifically to cholesterol, we measured cholesterol levels in 3T3 cells and SV101-3T3 cells. SV101-3T3 cells contained 50-100% more cholesterol per cell than 3T3 cells. Both cell types were starved for cholesterol by growth in lipid-depleted medium plus 25-hydroxycholesterol. The cholesterol level of SV101-3T3 cells decreased by 30-50%, while the level in 3T3 cells remained constant. Filipin-stained SV101-3T3 cells revealed bright patches of filipin under fluorescence microscopy. These patches were absent in 3T3 cells and in SV101-3T3 and 3T3 cells starved for cholesterol. We selectively labeled plasma membranes of these cells with a spin label analog of phosphatidylcholine. The spin label indicated differences in plasma membrane fluidity that may be related to the different cholesterol levels in 3T3 and SV101-3T3 cells."}
{"id": "PMID:232523", "title": "Tumorigenicity of revertant from an SV40-transformed line.", "content": "A syndrome of in vitro properties correlates with the tumorigenicity of SV40-transformed rodent cells. These properties are: plasminogen activator production, loss of large actin cables, and anchorage-independent growth. An established rat fibroblast line, its SV40 transformant, several T-antigen negative revertants, and a spontaneous retransformant isolated from one of the revertants were analyzed in vivo for their tumorigenicity and in vitro for the syndrome. The two transformed lines were highly tumorigenic, and had clearly abnormal in vitro properties. The parental rat line was weakly tumorigenic in nude mice and demonstrated a slightly transformed response in the in vitro assays. The revertants were completely nontumorigenic. Expression of the in vitro syndrome was not uniform for all revertants; however, most cell lines maintained the correlation of the syndrome and tumorigenicity.", "contents": "Tumorigenicity of revertant from an SV40-transformed line. A syndrome of in vitro properties correlates with the tumorigenicity of SV40-transformed rodent cells. These properties are: plasminogen activator production, loss of large actin cables, and anchorage-independent growth. An established rat fibroblast line, its SV40 transformant, several T-antigen negative revertants, and a spontaneous retransformant isolated from one of the revertants were analyzed in vivo for their tumorigenicity and in vitro for the syndrome. The two transformed lines were highly tumorigenic, and had clearly abnormal in vitro properties. The parental rat line was weakly tumorigenic in nude mice and demonstrated a slightly transformed response in the in vitro assays. The revertants were completely nontumorigenic. Expression of the in vitro syndrome was not uniform for all revertants; however, most cell lines maintained the correlation of the syndrome and tumorigenicity."}
{"id": "PMID:232524", "title": "Alteration of insulin binding and cytoskeletal organization in cultured fibroblasts by tertiary amine local anesthetics.", "content": "Tertiary amine local anesthetics cause a time- and dose-dependent, reversible increase in insulin binding sites in cultured chick embryo fibroblasts. Incubation of fibroblasts with 0.2 mM dibucaine for 3 h at 37 degrees C results in a twofold to threefold increase in insulin binding, with an increase in average number of binding sites (Ka = 3.0 X 10(7) M-1) from 9 X 10(3) per cell. Trypsin or ethyleneglycoltetraacetic acid (EGTA) alone increases insulin binding twofold to threefold, but fails to further increase 125I-insulin binding in cells pretreated with dibucaine. Transformation of chick embryo fibroblasts with Rous sarcoma virus causes a threefold to fivefold increase in insulin binding, which is not further increased by incubation with dibucaine. As demonstrated by transmission electron microscopy, dibucaine and trypsin also induce changes in the cytoskeleton of chick embryo fibroblasts, characterized by disorganization and disappearance of microfilament and microtubule bundles. These alterations are accompanied by gross morphologic changes, including rounding of cells and appearance of numerous ruffles and blebs on the cell surface. These observations are consistent with the hypothesis that expression of surface receptors in cultured chick embryo fibroblasts is related to the organization and disorganization of cytoskeletal structures.", "contents": "Alteration of insulin binding and cytoskeletal organization in cultured fibroblasts by tertiary amine local anesthetics. Tertiary amine local anesthetics cause a time- and dose-dependent, reversible increase in insulin binding sites in cultured chick embryo fibroblasts. Incubation of fibroblasts with 0.2 mM dibucaine for 3 h at 37 degrees C results in a twofold to threefold increase in insulin binding, with an increase in average number of binding sites (Ka = 3.0 X 10(7) M-1) from 9 X 10(3) per cell. Trypsin or ethyleneglycoltetraacetic acid (EGTA) alone increases insulin binding twofold to threefold, but fails to further increase 125I-insulin binding in cells pretreated with dibucaine. Transformation of chick embryo fibroblasts with Rous sarcoma virus causes a threefold to fivefold increase in insulin binding, which is not further increased by incubation with dibucaine. As demonstrated by transmission electron microscopy, dibucaine and trypsin also induce changes in the cytoskeleton of chick embryo fibroblasts, characterized by disorganization and disappearance of microfilament and microtubule bundles. These alterations are accompanied by gross morphologic changes, including rounding of cells and appearance of numerous ruffles and blebs on the cell surface. These observations are consistent with the hypothesis that expression of surface receptors in cultured chick embryo fibroblasts is related to the organization and disorganization of cytoskeletal structures."}
{"id": "PMID:232525", "title": "Modulation of cell surface iron transferrin receptors by cellular density and state of activation.", "content": "This report describes investigations of plasma membrane transferring receptors on a variety of lymphoid cell lines and normal peripheral blood lymphocytes during activation and cell growth cycles. Transformed lymphoid cell lines have as many as 1,000 times the number of receptors found on normal resting lymphocytes. The number of iron transferrin receptors on continuous cell lines as well as normal human fibroblasts is down-regulated during the transition from log-phase growth to stationary plateau growth. When normal lymphocytes are transformed by mixed lymphocyte culture or mitogens, they rapidly express a 50-fold increase in the number of transferrin binding sites. This appearance of iron transferrin receptors anticipates nuclear changes during cell activation and subsequent mitosis of normal cells.", "contents": "Modulation of cell surface iron transferrin receptors by cellular density and state of activation. This report describes investigations of plasma membrane transferring receptors on a variety of lymphoid cell lines and normal peripheral blood lymphocytes during activation and cell growth cycles. Transformed lymphoid cell lines have as many as 1,000 times the number of receptors found on normal resting lymphocytes. The number of iron transferrin receptors on continuous cell lines as well as normal human fibroblasts is down-regulated during the transition from log-phase growth to stationary plateau growth. When normal lymphocytes are transformed by mixed lymphocyte culture or mitogens, they rapidly express a 50-fold increase in the number of transferrin binding sites. This appearance of iron transferrin receptors anticipates nuclear changes during cell activation and subsequent mitosis of normal cells."}
{"id": "PMID:232526", "title": "Polyoma T (tumor) antigen species in abortively and stably transformed cells.", "content": "Stable neoplastic transformation of cells by polyoma virus requires the particpation of two viral genes, designated ts-a and hr-t. The effects of mutations in these two genes on the patterns of T-antigen synthesis during productive infection have been previously described: ts-a mutants are affected in the \"large\" (100K) nuclear T antigen, and hr-t mutants are affected in the \"middle\" (36K, 56K, 63K) and \"small\" (22K) T antigens. The latter are associated predominantly with the plasma membrane (56K) and cytosol fractions, respectively. Here we examine the expression of the various forms of polyoma T antigen in nonproductive infection (abortive transformation) as well as in stably transformed cell lines of different species. The results on abortive transformation are essentially the same as those described above for productive infection. In stably transformed cells, the middle and small T antigens are seen to various extents. The large T antigen, however, is often absent or present below the level of detection. Clones lacking the large T antigen are found most often among mouse transformants, but are also seen among rat transformants. Retention of the 100K species in transformed cells therefore appears to be, at least in part, an inverse function of the level of permissivity of the host toward productive viral infection. These findings indicate that the induction of the transformed phenotype in both abortively and stably transformed cells generally does not require the large T antigen, but rather the products of the hr-t gene.", "contents": "Polyoma T (tumor) antigen species in abortively and stably transformed cells. Stable neoplastic transformation of cells by polyoma virus requires the particpation of two viral genes, designated ts-a and hr-t. The effects of mutations in these two genes on the patterns of T-antigen synthesis during productive infection have been previously described: ts-a mutants are affected in the \"large\" (100K) nuclear T antigen, and hr-t mutants are affected in the \"middle\" (36K, 56K, 63K) and \"small\" (22K) T antigens. The latter are associated predominantly with the plasma membrane (56K) and cytosol fractions, respectively. Here we examine the expression of the various forms of polyoma T antigen in nonproductive infection (abortive transformation) as well as in stably transformed cell lines of different species. The results on abortive transformation are essentially the same as those described above for productive infection. In stably transformed cells, the middle and small T antigens are seen to various extents. The large T antigen, however, is often absent or present below the level of detection. Clones lacking the large T antigen are found most often among mouse transformants, but are also seen among rat transformants. Retention of the 100K species in transformed cells therefore appears to be, at least in part, an inverse function of the level of permissivity of the host toward productive viral infection. These findings indicate that the induction of the transformed phenotype in both abortively and stably transformed cells generally does not require the large T antigen, but rather the products of the hr-t gene."}
{"id": "PMID:232527", "title": "Effects of the tumor promoter TPA on the induction of DNA synthesis in normal and RSV-transformed rat fibroblasts.", "content": "Induction of DNA synthesis by the tumor promoter tetradecanoyl phorbol acetate (TPA) was studied in a line of cultured rat fibroblasts (Rat-1) and their Rous sarcoma virus-transformed derivative (Rat-1 (RSV)). Following serum deprivation for 54 h to achieve quiescence, semiconservative DNA replication was measured by incubation of cells in BrdUrd and FdUrd after serum stimulation in the presence or absence of TPA. Optimal concentrations of TPA (0.1--0.5 microgram/ml) in serum-free medium induced a small increase (10--15%) in the amount of DNA made over a 30-h period in both Rat-1 and Rat-1 (RSV) cells. When Rat-1 cells were stimulated by a 4-h serum pulse, 30% of the DNA was replicated by 30 h. If the serum pulse was followed by TPA addition, 70% DNA replication was observed. If the serum pulse was preceded by TPA addition, the onset of DNA synthesis was delayed by several houses, but stimulation of DNA synthesis occurred. In contrast, the Rat-1 (RSV) cells did not show an increased in DNA synthesis induced by TPA in similar protocols, but the serum-induced onset of DNA synthesis was delayed by several hours in the presence of TPA. Therefore, TPA acts as a co-inducer of DNA synthesis in the Rat-1 but not in the Rat-1 (RSV) cells. The parent alcohol, phorbol, was inactive in Rat-1 cells, but delayed the onset of DNA synthesis in the Rat-1 (RSV) cells. We conclude that the co-inducing and delaying activities of TPA on DNA synthesis appear to be distinct and to act a different points in the G1 phase of the cell cycle.", "contents": "Effects of the tumor promoter TPA on the induction of DNA synthesis in normal and RSV-transformed rat fibroblasts. Induction of DNA synthesis by the tumor promoter tetradecanoyl phorbol acetate (TPA) was studied in a line of cultured rat fibroblasts (Rat-1) and their Rous sarcoma virus-transformed derivative (Rat-1 (RSV)). Following serum deprivation for 54 h to achieve quiescence, semiconservative DNA replication was measured by incubation of cells in BrdUrd and FdUrd after serum stimulation in the presence or absence of TPA. Optimal concentrations of TPA (0.1--0.5 microgram/ml) in serum-free medium induced a small increase (10--15%) in the amount of DNA made over a 30-h period in both Rat-1 and Rat-1 (RSV) cells. When Rat-1 cells were stimulated by a 4-h serum pulse, 30% of the DNA was replicated by 30 h. If the serum pulse was followed by TPA addition, 70% DNA replication was observed. If the serum pulse was preceded by TPA addition, the onset of DNA synthesis was delayed by several houses, but stimulation of DNA synthesis occurred. In contrast, the Rat-1 (RSV) cells did not show an increased in DNA synthesis induced by TPA in similar protocols, but the serum-induced onset of DNA synthesis was delayed by several hours in the presence of TPA. Therefore, TPA acts as a co-inducer of DNA synthesis in the Rat-1 but not in the Rat-1 (RSV) cells. The parent alcohol, phorbol, was inactive in Rat-1 cells, but delayed the onset of DNA synthesis in the Rat-1 (RSV) cells. We conclude that the co-inducing and delaying activities of TPA on DNA synthesis appear to be distinct and to act a different points in the G1 phase of the cell cycle."}
{"id": "PMID:232528", "title": "Structural and functional alterations in the surface of vascular endothelial cells associated with the formation of a confluent cell monolayer and with the withdrawal of fibroblast growth factor.", "content": "Vascular endothelial cells cultured in the presence of fibroblast growth factor (FGF) divide actively when seeded at low or clonal cell densities and upon reaching confluence adopt a morphologic appearance and differentiated properties similar to those of the vascular endothelium in vivo. In this review, we present some of our recent observations regarding the characteristics (both structural and functional) of these endothelial cells and the role of FGF in controlling their proliferation and normal differentiation. At confluence the endothelial cells form a monolayer of closely apposed and nondividing cells that have a nonthrombogenic apical surface and can no longer internalize bound ligands such as low-density lipoprotein (LDL). The adoption of these properties is correlated and possibly causally related to changes in the cell surface such as the appearance of a 60,000 molecular weight protein (CSP-60); the disappearance of fibronectin from the apical cell surface and its concomitant accumulation in the basal lamina; and a restriction of the lateral mobility of various cell surface receptor sites. In contrast, endothelial cells that are maintained in the absence of FGF undergo within three passages alterations that are incompatible with their in vivo morphologic appearance and physiologic behavior. They grow at confluence on top of each other and hence can no longer adopt both the structural (CSP-60, cell surface polarity) and functional (barrier function, nonthrombogenicity) attributes of differentiated endothelial cells. Since these characteristics can be reacquired in response to readdition of FGF, in addition to being a mitogen FGF may also be involved in controlling the differentiation and phenotypic expression of the vascular endothelium.", "contents": "Structural and functional alterations in the surface of vascular endothelial cells associated with the formation of a confluent cell monolayer and with the withdrawal of fibroblast growth factor. Vascular endothelial cells cultured in the presence of fibroblast growth factor (FGF) divide actively when seeded at low or clonal cell densities and upon reaching confluence adopt a morphologic appearance and differentiated properties similar to those of the vascular endothelium in vivo. In this review, we present some of our recent observations regarding the characteristics (both structural and functional) of these endothelial cells and the role of FGF in controlling their proliferation and normal differentiation. At confluence the endothelial cells form a monolayer of closely apposed and nondividing cells that have a nonthrombogenic apical surface and can no longer internalize bound ligands such as low-density lipoprotein (LDL). The adoption of these properties is correlated and possibly causally related to changes in the cell surface such as the appearance of a 60,000 molecular weight protein (CSP-60); the disappearance of fibronectin from the apical cell surface and its concomitant accumulation in the basal lamina; and a restriction of the lateral mobility of various cell surface receptor sites. In contrast, endothelial cells that are maintained in the absence of FGF undergo within three passages alterations that are incompatible with their in vivo morphologic appearance and physiologic behavior. They grow at confluence on top of each other and hence can no longer adopt both the structural (CSP-60, cell surface polarity) and functional (barrier function, nonthrombogenicity) attributes of differentiated endothelial cells. Since these characteristics can be reacquired in response to readdition of FGF, in addition to being a mitogen FGF may also be involved in controlling the differentiation and phenotypic expression of the vascular endothelium."}
{"id": "PMID:232529", "title": "Regulation of dome formation in differentiated epithelial cell cultures.", "content": "Rat mammary (Rama 25) and dog kidney (MDCK) epithelial cell cultures formed 'domes' of cells due to fluid accumulation in focal regions between the culture dish and the cell monolayer. Addition of ouabain caused collapse of domes, suggesting that transport functions were required for maintenance of domes. Dome formation in both epithelial cell lines was stimulated by a broad spectrum of known inducers of erythroid differentiation in Fried erythroleukemia cells. Among these inducers were: 1) polar solvents such as dimethyl-sulfoxide, dimethylformamide, and hexamethylene bisacetamide; 2) purines such as hypoxanthine, inosine, and adenosine; 3) low-molecular-weight fatty acids such as n-butyrate; and 4) conditions expected to elevate levels of cyclic AMP. In the latter group were activators of adenylate cyclase such as cholera toxin and prostaglandin E 1; cyclic AMP phosphodiesterase inhibitors such as theophylline and 1-methyl-3-isobutylxanthine; and analogs of cyclic AMP. Induction of domes occurred 15--30 h after addition of inducer to the culture medium. Induction by chemicals was serum-dependent and required protein synthesis but not DNA synthesis. Induced dome formation was reversible after removal of inducer, requiring the continuous presence of inducer. Reversal was also observed after either either removal of serum or addition of inhibitors of protein synthesis. These results suggest that hypothesis that domes arise in these epithelial cultures by a process that is similar to cell differentiation and is influenced by cyclic AMP.", "contents": "Regulation of dome formation in differentiated epithelial cell cultures. Rat mammary (Rama 25) and dog kidney (MDCK) epithelial cell cultures formed 'domes' of cells due to fluid accumulation in focal regions between the culture dish and the cell monolayer. Addition of ouabain caused collapse of domes, suggesting that transport functions were required for maintenance of domes. Dome formation in both epithelial cell lines was stimulated by a broad spectrum of known inducers of erythroid differentiation in Fried erythroleukemia cells. Among these inducers were: 1) polar solvents such as dimethyl-sulfoxide, dimethylformamide, and hexamethylene bisacetamide; 2) purines such as hypoxanthine, inosine, and adenosine; 3) low-molecular-weight fatty acids such as n-butyrate; and 4) conditions expected to elevate levels of cyclic AMP. In the latter group were activators of adenylate cyclase such as cholera toxin and prostaglandin E 1; cyclic AMP phosphodiesterase inhibitors such as theophylline and 1-methyl-3-isobutylxanthine; and analogs of cyclic AMP. Induction of domes occurred 15--30 h after addition of inducer to the culture medium. Induction by chemicals was serum-dependent and required protein synthesis but not DNA synthesis. Induced dome formation was reversible after removal of inducer, requiring the continuous presence of inducer. Reversal was also observed after either either removal of serum or addition of inhibitors of protein synthesis. These results suggest that hypothesis that domes arise in these epithelial cultures by a process that is similar to cell differentiation and is influenced by cyclic AMP."}
{"id": "PMID:232533", "title": "[Lysozyme activity in the saliva of industrial workers exposed to fluorine compounds].", "content": "The authors performed investigations in Phosphoric Fertilizers Works in Gda\u0144sk to find out whether or not the work environment contaminated by fluorine compounds affects the activity of lysozome--the protective enzyme of saliva. In some in vitro experiments lysozome activity in exposed workers' saliva was found to be significantly lowered, as opposed to that in unexposed workers. In vivo experiments did not indicate any effects of work conditions on the activity of this enzyme. The obtained results, in vivo and in vitro, do not demonstrate any clear effects of work environment in the Phosphoric Fertilizers Works in Gda\u0144sk, upon lysozome activity in workers' saliva.", "contents": "[Lysozyme activity in the saliva of industrial workers exposed to fluorine compounds]. The authors performed investigations in Phosphoric Fertilizers Works in Gda\u0144sk to find out whether or not the work environment contaminated by fluorine compounds affects the activity of lysozome--the protective enzyme of saliva. In some in vitro experiments lysozome activity in exposed workers' saliva was found to be significantly lowered, as opposed to that in unexposed workers. In vivo experiments did not indicate any effects of work conditions on the activity of this enzyme. The obtained results, in vivo and in vitro, do not demonstrate any clear effects of work environment in the Phosphoric Fertilizers Works in Gda\u0144sk, upon lysozome activity in workers' saliva."}
{"id": "PMID:232536", "title": "Strain characteristics and features of ocular infection of herpes simplex virus type 1 isolates.", "content": "Herpes simplex virus type 1 isolates from 63 patients with herpetic keratoconjunctivitis were investigated. For the purpose of detecting strain differences neurovirulence was determined in mice, and viral DNA's were analyzed by digestion with EcoRI and Hind III restriction endonucleases. Neurovirulence differed by a factor up to 10(5) between individual strains and proved to be independent of the ratio between infectious and noninfectious particles in the stocks used. The endonuclease cleavage patterns revealed differences of the viral DNA structure which permitted us to distinguish seven clusters of strains. Correlations between neurovirulence and DNA markers could not be established nor could correlations be found between these markers and features of disease. The main reason for not finding a relationship in the latter case may be attributed to the significant role of host factors in the course of herpetic diseases.", "contents": "Strain characteristics and features of ocular infection of herpes simplex virus type 1 isolates. Herpes simplex virus type 1 isolates from 63 patients with herpetic keratoconjunctivitis were investigated. For the purpose of detecting strain differences neurovirulence was determined in mice, and viral DNA's were analyzed by digestion with EcoRI and Hind III restriction endonucleases. Neurovirulence differed by a factor up to 10(5) between individual strains and proved to be independent of the ratio between infectious and noninfectious particles in the stocks used. The endonuclease cleavage patterns revealed differences of the viral DNA structure which permitted us to distinguish seven clusters of strains. Correlations between neurovirulence and DNA markers could not be established nor could correlations be found between these markers and features of disease. The main reason for not finding a relationship in the latter case may be attributed to the significant role of host factors in the course of herpetic diseases."}
{"id": "PMID:232537", "title": "Infection and persistence of varicella-zoster virus in lymphoblastoid Raji cell line.", "content": "Infection of Raji cells by varicella-zoster virus (VZV) resulted in permissive infection with establishment of a persistently infected lymphoblastoid cell line. VZV antigens of the membrane and nuclear type, as detected by the indirect immunofluorescence membrane antigen (IFAMA) and anticomplement immunofluorescence (ACIF) tests, were observed. Minute amounts of infectious virus were detected by co-cultivation of VZV-infected Raji cells (Raji-VZV), with permissive human embryo fibroblasts (HEF). The virus isolated was found to be similar to the parent strain. Transient induction of Epstein-Barr viral capsid antigen (EB-VCA) was also observed. The persistently infected Raji-VZV cell line, when free of EB-VCA, was found suitable for measuring antibodies to varicella-zoster virus. The possible interaction in the infected Raji cells between EBV, which is implicated in human malignancy, and VZV which belongs also to the herpes group of viruses, is discussed.", "contents": "Infection and persistence of varicella-zoster virus in lymphoblastoid Raji cell line. Infection of Raji cells by varicella-zoster virus (VZV) resulted in permissive infection with establishment of a persistently infected lymphoblastoid cell line. VZV antigens of the membrane and nuclear type, as detected by the indirect immunofluorescence membrane antigen (IFAMA) and anticomplement immunofluorescence (ACIF) tests, were observed. Minute amounts of infectious virus were detected by co-cultivation of VZV-infected Raji cells (Raji-VZV), with permissive human embryo fibroblasts (HEF). The virus isolated was found to be similar to the parent strain. Transient induction of Epstein-Barr viral capsid antigen (EB-VCA) was also observed. The persistently infected Raji-VZV cell line, when free of EB-VCA, was found suitable for measuring antibodies to varicella-zoster virus. The possible interaction in the infected Raji cells between EBV, which is implicated in human malignancy, and VZV which belongs also to the herpes group of viruses, is discussed."}
{"id": "PMID:232538", "title": "Muscle and nerve changes induced by perhexiline maleate in man and mice.", "content": "Perhexiline maleate therapy may produce a polyneuropathy as well as other side effects in man. The Schwann-cell origin of the neuropathy is demonstrated by morphologic studies. Ultrastructural studies of muscle and nerve biopsies showed the presence of intracytoplasmic inclusions, primarily in Schwann cells, muscle fibers, and endothelial cells. These inclusions were polymorphic and varied from one cell type to another. They were frequently associated with calcium deposits, and their structure suggested a lysosomal origin. It was possible experimentally to reproduce similar inclusions in mice. Furthermore, numerous tubular aggregates were observed in intoxicated mouse muscle fibers.", "contents": "Muscle and nerve changes induced by perhexiline maleate in man and mice. Perhexiline maleate therapy may produce a polyneuropathy as well as other side effects in man. The Schwann-cell origin of the neuropathy is demonstrated by morphologic studies. Ultrastructural studies of muscle and nerve biopsies showed the presence of intracytoplasmic inclusions, primarily in Schwann cells, muscle fibers, and endothelial cells. These inclusions were polymorphic and varied from one cell type to another. They were frequently associated with calcium deposits, and their structure suggested a lysosomal origin. It was possible experimentally to reproduce similar inclusions in mice. Furthermore, numerous tubular aggregates were observed in intoxicated mouse muscle fibers."}
{"id": "PMID:232543", "title": "Cyclic 3',5'-adenosine monophosphate phosphodiesterase (cAMP PDE) and cyclic 3',5'-guanosine monophosphate phosphodiesterase (cGMP PDE) in microvessels isolated from bovine cortex.", "content": "It was established that microvessels of a bovine cortex exhibit significant cyclic 3',5'-adenosine monophosphate phosphodiesterase (cAMP PDE) and cyclic 3',5'-guanosine monophosphate phosphodiesterase (cGMP PDE) activities. These activities are dependent on the presence of Mg2+. Absence of Ca2+ was virtually without effect. When both Mg2+ and Ca2+ were absent, PDE activities increased compared with activities observed in the absence of Mg2+. Xanthines (caffeine, theobromine, and theophylline) were better inhibitors of cAMP PDE than of cGMP PDE. Imidazole, in very high concentration (1 X 10(-2) M) only, exhibited PDE stimulatory activity at high concentrations of both substrates. Otherwise, it exhibited PDE-inhibitory properties.", "contents": "Cyclic 3',5'-adenosine monophosphate phosphodiesterase (cAMP PDE) and cyclic 3',5'-guanosine monophosphate phosphodiesterase (cGMP PDE) in microvessels isolated from bovine cortex. It was established that microvessels of a bovine cortex exhibit significant cyclic 3',5'-adenosine monophosphate phosphodiesterase (cAMP PDE) and cyclic 3',5'-guanosine monophosphate phosphodiesterase (cGMP PDE) activities. These activities are dependent on the presence of Mg2+. Absence of Ca2+ was virtually without effect. When both Mg2+ and Ca2+ were absent, PDE activities increased compared with activities observed in the absence of Mg2+. Xanthines (caffeine, theobromine, and theophylline) were better inhibitors of cAMP PDE than of cGMP PDE. Imidazole, in very high concentration (1 X 10(-2) M) only, exhibited PDE stimulatory activity at high concentrations of both substrates. Otherwise, it exhibited PDE-inhibitory properties."}
{"id": "PMID:232540", "title": "Animal models of alcoholic neuropathy: morphologic, electrophysiologic, and biochemical findings.", "content": "A chronic high alcohol intake was induced in rats through the use of two procedures: the schedule-induced polydipsia technique and the liquid diet technique. Rats consumed 11-12 g of ethanol per kilogram body weight per day for 16 to 18 weeks. Morphologic evidence of a mild distal axonal neuropathy in the ventral caudal nerve was proposed. The red blood cell transketolase levels were normal, indicating that the rats were not deficient in thiamine and suggesting that the axonal degeneration was due to the direct toxic effect of alcohol. Axonal transport studies demonstrated a significant increase in the amount of acetylcholinesterase transported in an orthograde direction in the sciatic nerves of alcohol-exposed rats, and indicated no change in the transport of choline acetyltransferase or in the specific binding of colchicine by neurotubulin.", "contents": "Animal models of alcoholic neuropathy: morphologic, electrophysiologic, and biochemical findings. A chronic high alcohol intake was induced in rats through the use of two procedures: the schedule-induced polydipsia technique and the liquid diet technique. Rats consumed 11-12 g of ethanol per kilogram body weight per day for 16 to 18 weeks. Morphologic evidence of a mild distal axonal neuropathy in the ventral caudal nerve was proposed. The red blood cell transketolase levels were normal, indicating that the rats were not deficient in thiamine and suggesting that the axonal degeneration was due to the direct toxic effect of alcohol. Axonal transport studies demonstrated a significant increase in the amount of acetylcholinesterase transported in an orthograde direction in the sciatic nerves of alcohol-exposed rats, and indicated no change in the transport of choline acetyltransferase or in the specific binding of colchicine by neurotubulin."}
{"id": "PMID:232544", "title": "Studies on the glycoprotein component of (Na+-k+) atpase from guinea pig brain.", "content": "In this study an attempt was made to elucidate the possible mechanism of the brain microsomal (Na+-K+)ATPase inhibition based on the assumption that glycoprotein part of the enzyme is exposed on the outer membrane surface. In our experiments the modification with concanavalin A of sugar end groups exposed by neuraminidase treatment resulted in a significant decrease of the brain (Na+-K+)ATPase activity. The percentage of the enzyme inhibition by concanavalin A binding to the neuraminidase-treated preparation corresponds to the amount of liberated sialic acids. The modification of the glycoprotein part of the brain (Na+-K+)ATPase complex by neuraminidase and concanavalin A treatments did not affect K+-nitrophenylphosphatase activity.", "contents": "Studies on the glycoprotein component of (Na+-k+) atpase from guinea pig brain. In this study an attempt was made to elucidate the possible mechanism of the brain microsomal (Na+-K+)ATPase inhibition based on the assumption that glycoprotein part of the enzyme is exposed on the outer membrane surface. In our experiments the modification with concanavalin A of sugar end groups exposed by neuraminidase treatment resulted in a significant decrease of the brain (Na+-K+)ATPase activity. The percentage of the enzyme inhibition by concanavalin A binding to the neuraminidase-treated preparation corresponds to the amount of liberated sialic acids. The modification of the glycoprotein part of the brain (Na+-K+)ATPase complex by neuraminidase and concanavalin A treatments did not affect K+-nitrophenylphosphatase activity."}
{"id": "PMID:232545", "title": "beta-Adrenergic receptors of frog erythrocytes. Biochemical sequelae following stimulation with isoproterenol.", "content": "Following persistent stimulation of beta-adrenergic receptors of frog erythrocytes with (-)-isoproterenol, the cyclic adenosine 3',5'-monophosphate-dependent protein kinase (cAMP-dependent protein kinase) (EC 2.7.1.37) was activated for several hours. This activation outlasted the duration of the increase of cAMP content. Following a persistant stimulation of beta-adrenergic receptors with isoproterenol, the phosphorylation of selective membrane proteins was increased. This increase in phosphorylation lasted longer than 4 hr but less than 12 hr. Between 2 and 4 hr after receptor stimulation the loss of beta-adrenergic receptor from plasma membrane was maximal, and the phosphorylation of two membrane proteins characterized by molecular weights of 60,000 and 38,000 daltons was selectively enhanced. In addition we found that isolated erythrocytes are capable of synthesizing RNA and polypeptides and that incubation with (-)-isoproterenol indices a long-term delayed increase of the synthesis of erythrocyte proteins. This increase in the synthesis of proteins appears to require new RNA synthesis. Thus the possibility can be entertained that this delayed increase in protein synthesis participates in the new synthesis of receptor and is operative in the termination of beta-adrenergic receptor subsensitivity elicited by a persistent stimulation with (-)-isoproterenol.", "contents": "beta-Adrenergic receptors of frog erythrocytes. Biochemical sequelae following stimulation with isoproterenol. Following persistent stimulation of beta-adrenergic receptors of frog erythrocytes with (-)-isoproterenol, the cyclic adenosine 3',5'-monophosphate-dependent protein kinase (cAMP-dependent protein kinase) (EC 2.7.1.37) was activated for several hours. This activation outlasted the duration of the increase of cAMP content. Following a persistant stimulation of beta-adrenergic receptors with isoproterenol, the phosphorylation of selective membrane proteins was increased. This increase in phosphorylation lasted longer than 4 hr but less than 12 hr. Between 2 and 4 hr after receptor stimulation the loss of beta-adrenergic receptor from plasma membrane was maximal, and the phosphorylation of two membrane proteins characterized by molecular weights of 60,000 and 38,000 daltons was selectively enhanced. In addition we found that isolated erythrocytes are capable of synthesizing RNA and polypeptides and that incubation with (-)-isoproterenol indices a long-term delayed increase of the synthesis of erythrocyte proteins. This increase in the synthesis of proteins appears to require new RNA synthesis. Thus the possibility can be entertained that this delayed increase in protein synthesis participates in the new synthesis of receptor and is operative in the termination of beta-adrenergic receptor subsensitivity elicited by a persistent stimulation with (-)-isoproterenol."}
{"id": "PMID:232546", "title": "Phosphorus 31 NMR of neuroblastoma clonal lines. Effect of cell confluency state and dibutyryl cyclic AMP.", "content": "Phosphorus nuclear magnetic resonance is used to study changes in the levels of the major phosphate-containing intermediary metabolites concomitant with induced cellular differentiation in the N-18 and C-46 neuroblastoma clonal lines. The study reveals differences between the 31P-NMR profiles of the two clonal lines and also striking differences attendant to dibutyryl cAMP-mediated morphological differentiation in the N-18 clone. Phosphorus-31 NMR would appear to provide a new technique with which to study genetic differentiation.", "contents": "Phosphorus 31 NMR of neuroblastoma clonal lines. Effect of cell confluency state and dibutyryl cyclic AMP. Phosphorus nuclear magnetic resonance is used to study changes in the levels of the major phosphate-containing intermediary metabolites concomitant with induced cellular differentiation in the N-18 and C-46 neuroblastoma clonal lines. The study reveals differences between the 31P-NMR profiles of the two clonal lines and also striking differences attendant to dibutyryl cAMP-mediated morphological differentiation in the N-18 clone. Phosphorus-31 NMR would appear to provide a new technique with which to study genetic differentiation."}
{"id": "PMID:232548", "title": "Lacrimal gland and fossa lesions: an approach to diagnosis and management.", "content": "Lesions of the fossa of the lacrimal gland present special problems in diagnosis and management. Clinical recognition and differentiation of benign mixed cell lacrimal gland tumors from other inflammatory and neoplastic lesions of the lacrimal gland fossa are feasible and should provide the basis for the approach to proper management. Lesions conforming to the clinical picture of benign mixed cell lacrimal gland tumors need not undergo incisional biopsy, but require en bloc excision with adjacent tissues through a lateral orbitotomy to ensure complete excision and to prevent late recurrence. Incisional biopsy is indicated and should not be delayed in suspected infectious and noninfectious inflammatory lesions that have not responded rapidly to medical therapy, and in other lesions suspected of being neoplastic and not amenable to total local excision. An expedient approach to these lesions is essential if the prognosis of epithelial lacrimal gland neoplasms is to be improved.", "contents": "Lacrimal gland and fossa lesions: an approach to diagnosis and management. Lesions of the fossa of the lacrimal gland present special problems in diagnosis and management. Clinical recognition and differentiation of benign mixed cell lacrimal gland tumors from other inflammatory and neoplastic lesions of the lacrimal gland fossa are feasible and should provide the basis for the approach to proper management. Lesions conforming to the clinical picture of benign mixed cell lacrimal gland tumors need not undergo incisional biopsy, but require en bloc excision with adjacent tissues through a lateral orbitotomy to ensure complete excision and to prevent late recurrence. Incisional biopsy is indicated and should not be delayed in suspected infectious and noninfectious inflammatory lesions that have not responded rapidly to medical therapy, and in other lesions suspected of being neoplastic and not amenable to total local excision. An expedient approach to these lesions is essential if the prognosis of epithelial lacrimal gland neoplasms is to be improved."}
{"id": "PMID:232552", "title": "[Angioimmunoblastic lymphadenopathy: ultrastructural study of lymph nodes. Possible relationship with Epstein-Barr Virus (EBV) (author's transl)].", "content": "Angioimmunoblastic lymphadenopathy (AIL) has been clinically and histopathologically described by several authors since 1972, but only a few papers have analyzed the morphological aspects of the lymph nodes as observed by using electron microscopy. In the past three years, we happened to see in the Curie Institute two typical cases of AIL, both of whose clinical and immunological data are briefly reported in this paper. We describe some peculiar patterns observed on the lymph nodes during the acute phase of the disease, by examination of semithin sections and electron-microscopic preparations. As have many others, we found strong diffuse B-lymphocyte proliferation, but we must emphasize that many plasmocytes had an obvious defect in cell maturation, but no monomorphous defect. We noted that the predominant postcapillary venules had hypertrophied endothelial and perithelial cells, and multilayering basal lamina. We found some unusual features such as lymphocyte and/or plasmocyte phagocytosis by macrophages, or the atypical aspect of eosinophilic granulations. Finally, in the cytoplasm of a few transformed lymphocytes we detected some viral-like particles resembling herpes virus. Whether this last finding may have been related to the pathogeny of AIL could not be resolved by using morphological techniques. In the second part of this paper, we discuss the etiology of the disease, taking in account our clinical, immunological, and morphological observations. The possible relation of AIL to infectious mononucleosis, and the hypothetical role of Epstein-Barr virus are discussed.", "contents": "[Angioimmunoblastic lymphadenopathy: ultrastructural study of lymph nodes. Possible relationship with Epstein-Barr Virus (EBV) (author's transl)]. Angioimmunoblastic lymphadenopathy (AIL) has been clinically and histopathologically described by several authors since 1972, but only a few papers have analyzed the morphological aspects of the lymph nodes as observed by using electron microscopy. In the past three years, we happened to see in the Curie Institute two typical cases of AIL, both of whose clinical and immunological data are briefly reported in this paper. We describe some peculiar patterns observed on the lymph nodes during the acute phase of the disease, by examination of semithin sections and electron-microscopic preparations. As have many others, we found strong diffuse B-lymphocyte proliferation, but we must emphasize that many plasmocytes had an obvious defect in cell maturation, but no monomorphous defect. We noted that the predominant postcapillary venules had hypertrophied endothelial and perithelial cells, and multilayering basal lamina. We found some unusual features such as lymphocyte and/or plasmocyte phagocytosis by macrophages, or the atypical aspect of eosinophilic granulations. Finally, in the cytoplasm of a few transformed lymphocytes we detected some viral-like particles resembling herpes virus. Whether this last finding may have been related to the pathogeny of AIL could not be resolved by using morphological techniques. In the second part of this paper, we discuss the etiology of the disease, taking in account our clinical, immunological, and morphological observations. The possible relation of AIL to infectious mononucleosis, and the hypothetical role of Epstein-Barr virus are discussed."}
{"id": "PMID:232553", "title": "Psychologic correlates of serum indicators of stress in man: a longitudinal study.", "content": "Correlations between serum uric acid, cortisol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and psychometric indices of stress--namely, anxiety, hostility, and depression--were investigated in 20 students over a 2 1/2 month academic quarter. There were three peak periods of stress, with two occurring during midterm and final exams. The observed changes in serum cortisol were highly correlated with changes in anxiety and depression. Serum uric acid was significantly depressed during the first half of the quarter, but returned to control levels after midterm exams. Serum cholesterol and the LDL cholesterol subfraction were significantly elevated above control levels and remained elevated throughout the quarter after the first day of classes. Absolute levels of HDL cholesterol varied little throughout the quarter, however, the ratio of HDL cholesterol/total cholesterol was significantly depressed twice in the quarter, each time following approximately 10 days after the peak period of stress.", "contents": "Psychologic correlates of serum indicators of stress in man: a longitudinal study. Correlations between serum uric acid, cortisol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and psychometric indices of stress--namely, anxiety, hostility, and depression--were investigated in 20 students over a 2 1/2 month academic quarter. There were three peak periods of stress, with two occurring during midterm and final exams. The observed changes in serum cortisol were highly correlated with changes in anxiety and depression. Serum uric acid was significantly depressed during the first half of the quarter, but returned to control levels after midterm exams. Serum cholesterol and the LDL cholesterol subfraction were significantly elevated above control levels and remained elevated throughout the quarter after the first day of classes. Absolute levels of HDL cholesterol varied little throughout the quarter, however, the ratio of HDL cholesterol/total cholesterol was significantly depressed twice in the quarter, each time following approximately 10 days after the peak period of stress."}
{"id": "PMID:232556", "title": "Yielding ability of erect- and narrow-leaved rice mutant in heavy manuring and dense planting culture.", "content": "A dwarf rice mutant was induced through the chronic exposure of 60Co gamma-rays. This mutant was crossed with a heavy-panicle type variety, and semi-dwarf plants permitting a more efficient distribution of light within the canopy were obtained. They along with current commercial varieties and the parent mutant were assessed for yield components, the yielding ability at three levels of nitrogen fertilizer by varying plant density and several other agronomic traits. The ssmidwarf rice possessed significantly higher rates of net photosynthetic CO2 uptake compared with that of current commercial varieties, and it was improved in yield return by increasing nitrogen application. Manner of display of leaves could be manipulated by induced mutations.", "contents": "Yielding ability of erect- and narrow-leaved rice mutant in heavy manuring and dense planting culture. A dwarf rice mutant was induced through the chronic exposure of 60Co gamma-rays. This mutant was crossed with a heavy-panicle type variety, and semi-dwarf plants permitting a more efficient distribution of light within the canopy were obtained. They along with current commercial varieties and the parent mutant were assessed for yield components, the yielding ability at three levels of nitrogen fertilizer by varying plant density and several other agronomic traits. The ssmidwarf rice possessed significantly higher rates of net photosynthetic CO2 uptake compared with that of current commercial varieties, and it was improved in yield return by increasing nitrogen application. Manner of display of leaves could be manipulated by induced mutations."}
{"id": "PMID:232562", "title": "Activity of human hippocampal formation and amygdala neurons during sleep.", "content": "Fine wire microelectrodes were implanted for diagnostic purposes in 17 patients suffering from psychomotor epilepsy. Single- and multiunit activity during waking and natural nocturnal slow wave sleep and REM sleep was recorded in the hippocampus (n = 42), hippocampal gyrus (n = 53), and amygdala (n = 32). The firing rates of hippocampal gyrus units usually decreased during slow wave sleep and then increased to levels equal to or above waking during REM. In contrast, the firing rates of hippocampal neurons generally increased during slow wave sleep and fell to very low levels during REM. The amygdala presented a more mixed pattern. Since the projection from the hippocampal gyrus to hippocampus is excitatory, their opposite patterns during sleep suggest that the tonic firing patterns of HC neurons may be mainly the result of subcortical afferents.", "contents": "Activity of human hippocampal formation and amygdala neurons during sleep. Fine wire microelectrodes were implanted for diagnostic purposes in 17 patients suffering from psychomotor epilepsy. Single- and multiunit activity during waking and natural nocturnal slow wave sleep and REM sleep was recorded in the hippocampus (n = 42), hippocampal gyrus (n = 53), and amygdala (n = 32). The firing rates of hippocampal gyrus units usually decreased during slow wave sleep and then increased to levels equal to or above waking during REM. In contrast, the firing rates of hippocampal neurons generally increased during slow wave sleep and fell to very low levels during REM. The amygdala presented a more mixed pattern. Since the projection from the hippocampal gyrus to hippocampus is excitatory, their opposite patterns during sleep suggest that the tonic firing patterns of HC neurons may be mainly the result of subcortical afferents."}
{"id": "PMID:232563", "title": "Opioid effects on computer-derived sleep and EEG parameters in nondependent human addicts.", "content": "After one adaptation night, intramuscular doses of methadone (7.5, 15, 30 mg/70 kg), morphine (10 or 20 mg/70 kg), or placebo were given to seven male nondependent opiate addicts at weekly intervals in a randomized cross-over design. After three adaptation nights, heroin (3, 6, 12 mg/70 kg) was compared with morphine and placebo by means of a similar design in seven other subjects. Using electroencephalogram (EEG) bisector analysis, tape recordings of sleep were analyzed for two beta, three alpha, three theta, and two delta EEG patterns, as well as for detections of sleep spindles, K-complexes, eye movements, body movements, average electromyogram (EMG), and calculation of seven sleep-waking stages. All three opioids produce a dose-related arousal: they increase EMG and EEG measures of muscle activity, as well as body movements and EEG alpha, while decreasing EEG theta and spindling. These opioids also increase measures of waking state and decrease measures of spindle sleep and REM sleep. Although the 1974 version of the EEG bisector analysis is not exactly comparable to visual analysis, in this design it defined significant drug effects on sleep and EEG. Distinctive bisector analysis patterns are positively correlated with each sleep--waking stage.", "contents": "Opioid effects on computer-derived sleep and EEG parameters in nondependent human addicts. After one adaptation night, intramuscular doses of methadone (7.5, 15, 30 mg/70 kg), morphine (10 or 20 mg/70 kg), or placebo were given to seven male nondependent opiate addicts at weekly intervals in a randomized cross-over design. After three adaptation nights, heroin (3, 6, 12 mg/70 kg) was compared with morphine and placebo by means of a similar design in seven other subjects. Using electroencephalogram (EEG) bisector analysis, tape recordings of sleep were analyzed for two beta, three alpha, three theta, and two delta EEG patterns, as well as for detections of sleep spindles, K-complexes, eye movements, body movements, average electromyogram (EMG), and calculation of seven sleep-waking stages. All three opioids produce a dose-related arousal: they increase EMG and EEG measures of muscle activity, as well as body movements and EEG alpha, while decreasing EEG theta and spindling. These opioids also increase measures of waking state and decrease measures of spindle sleep and REM sleep. Although the 1974 version of the EEG bisector analysis is not exactly comparable to visual analysis, in this design it defined significant drug effects on sleep and EEG. Distinctive bisector analysis patterns are positively correlated with each sleep--waking stage."}
{"id": "PMID:232564", "title": "Sentence memory and sleep: a pilot study.", "content": "In four consecutive weekly sessions 12 subjects, aged 20--25 years, listened to a sentence stimulus before the onset of sleep and were asked to reproduce it after an awakening provoked during stage 2 or REM sleep of the first cycle. Recall of the sentence stimuli heard before sleep was affected by their semantic acceptability, but was unaffected by the sleep type (REM/NREM) or by the length of waking preceding sleep. The differing retention intervals involved for the recall tests after REM and NREM sleep may, however, have masked any effect of the former on recall.", "contents": "Sentence memory and sleep: a pilot study. In four consecutive weekly sessions 12 subjects, aged 20--25 years, listened to a sentence stimulus before the onset of sleep and were asked to reproduce it after an awakening provoked during stage 2 or REM sleep of the first cycle. Recall of the sentence stimuli heard before sleep was affected by their semantic acceptability, but was unaffected by the sleep type (REM/NREM) or by the length of waking preceding sleep. The differing retention intervals involved for the recall tests after REM and NREM sleep may, however, have masked any effect of the former on recall."}
{"id": "PMID:232565", "title": "Phasic events of REM sleep: phenomenology of middle ear muscle activity and periorbital integrated potentials in the same normal population.", "content": "Both periorbital integrated potentials (PIPs) and middle ear muscle activity (MEMAs) were recorded in a sample of normal male veterans. Activity measures were constructed for each REM period and for the 10 min preceding and following each REM period. PIPs and MEMAs displayed high levels of internight reliability. PIPs were more abundant than MEMAs; in REM the average PIP rate was almost 8 times the average MEMA rate. Within REM, the proportion of MEMAs and PIPs with concurrent eye movement activity was very similar, 66 and 70%, respectively. Both PIPs and MEMAs had higher rates within REM than within NREM. NREM PIP activity was similar both before and after the REM period, whereas NREM MEMA activity was higher before the REM period than after the REM period. Within REM, the distribution of PIPs and MEMAs was similar for REM periods exceeding 30 min. Within-night trends could nor be established for MEMAs due to limitations of the recording technique; PIPs, however, were generally highest in the middle of the night but still higher at the end of the night than at the beginning. Correlations with psychometric test data showed PIP rate in REM to be related to the psychoticism scale of the Minnesota Multiphasic Personality Inventory and MEMA rate in REM to be inversely related to the Barron Ego Strength scale. No associations were found between the psychometric data and measures of PIP and MEMA leakage from REM into NREM. The potential for pathological intrusion of REM phasic events into the waking stage might be conceptualized in terms of a general ungating of activity with PIP and MEMA rates increasing in both NREM and REM alike.", "contents": "Phasic events of REM sleep: phenomenology of middle ear muscle activity and periorbital integrated potentials in the same normal population. Both periorbital integrated potentials (PIPs) and middle ear muscle activity (MEMAs) were recorded in a sample of normal male veterans. Activity measures were constructed for each REM period and for the 10 min preceding and following each REM period. PIPs and MEMAs displayed high levels of internight reliability. PIPs were more abundant than MEMAs; in REM the average PIP rate was almost 8 times the average MEMA rate. Within REM, the proportion of MEMAs and PIPs with concurrent eye movement activity was very similar, 66 and 70%, respectively. Both PIPs and MEMAs had higher rates within REM than within NREM. NREM PIP activity was similar both before and after the REM period, whereas NREM MEMA activity was higher before the REM period than after the REM period. Within REM, the distribution of PIPs and MEMAs was similar for REM periods exceeding 30 min. Within-night trends could nor be established for MEMAs due to limitations of the recording technique; PIPs, however, were generally highest in the middle of the night but still higher at the end of the night than at the beginning. Correlations with psychometric test data showed PIP rate in REM to be related to the psychoticism scale of the Minnesota Multiphasic Personality Inventory and MEMA rate in REM to be inversely related to the Barron Ego Strength scale. No associations were found between the psychometric data and measures of PIP and MEMA leakage from REM into NREM. The potential for pathological intrusion of REM phasic events into the waking stage might be conceptualized in terms of a general ungating of activity with PIP and MEMA rates increasing in both NREM and REM alike."}
{"id": "PMID:232566", "title": "Effect of thyroxine on sleep in the rat.", "content": "The relationships between daily sleep time and metabolic rate both in phylogeny and ontogeny have suggested that sleep functions in the regulation of an animal's energy expenditure. Smaller animals may sleep more to conserve more energy. The present study investigated whether, in individual animals, sleep increased in response to the administration of thyroxine, which increased metabolic rate. The sleep, motor activity, food intake, and weights of rats were sampled over a base-line period of 2--4 weeks, during 2--6 weeks of daily administration of thyroxine (150 or 300 microgram/kg), and during a recovery period of 2--4 weeks. In addition to comparisons among base-line, drug, and recovery periods, comparisons were also made with control animals recorded at the same time. Thyroxine produced the increases in food intake and decreases in weight gain which usually accompany increases in metabolic rate. In spite of this evidence of major systemic adjustments in energy input (increased food intake) and energy output (decreased growth) in response to the increased energy expenditure of a raised metabolic rate, there was no change in total sleep time. Therefore, the results do not support the theory that sleep adapts to prevailing energy demands. Although the rate of cycling through the sleep stages is also related to metabolic rate both in phylogeny and ontogeny, in this study thyroxine did not change the period of paradoxical sleep rhythm.", "contents": "Effect of thyroxine on sleep in the rat. The relationships between daily sleep time and metabolic rate both in phylogeny and ontogeny have suggested that sleep functions in the regulation of an animal's energy expenditure. Smaller animals may sleep more to conserve more energy. The present study investigated whether, in individual animals, sleep increased in response to the administration of thyroxine, which increased metabolic rate. The sleep, motor activity, food intake, and weights of rats were sampled over a base-line period of 2--4 weeks, during 2--6 weeks of daily administration of thyroxine (150 or 300 microgram/kg), and during a recovery period of 2--4 weeks. In addition to comparisons among base-line, drug, and recovery periods, comparisons were also made with control animals recorded at the same time. Thyroxine produced the increases in food intake and decreases in weight gain which usually accompany increases in metabolic rate. In spite of this evidence of major systemic adjustments in energy input (increased food intake) and energy output (decreased growth) in response to the increased energy expenditure of a raised metabolic rate, there was no change in total sleep time. Therefore, the results do not support the theory that sleep adapts to prevailing energy demands. Although the rate of cycling through the sleep stages is also related to metabolic rate both in phylogeny and ontogeny, in this study thyroxine did not change the period of paradoxical sleep rhythm."}
{"id": "PMID:232567", "title": "Home and laboratory dreams: four empirical studies and a conceptual reevaluation.", "content": "Four empirical studies were presented on how the setting in which dreams are collected may influence the reporting and content of dreams of children on REM awakenings. In these studies it was shown that (1) with constant dream-sampling procedures, home and laboratory did not differ in the degree to which dream reports could be elicited from 4/5 year old children; (2) the rate of truly spontaneous reporting of dreams at home by 6/7 year olds is so minimal as to render these dreams an unfit base for generalization to typical dream life at these ages; (3) with constant dream sampling procedures, home and laboratory reports were not significantly different in content for 10/11 year olds; (4) results typically observed in uncontrolled home versus laboratory studies are replicable at the child level (ages 12/13), but probably reflect biased recall at home rather than effects of REM-monitoring procedures in the laboratory. The extant literature on home versus laboratory dream differences was reviewed, and it was concluded that even for normative dream studies, the REM-monitoring procedure is the method of choice.", "contents": "Home and laboratory dreams: four empirical studies and a conceptual reevaluation. Four empirical studies were presented on how the setting in which dreams are collected may influence the reporting and content of dreams of children on REM awakenings. In these studies it was shown that (1) with constant dream-sampling procedures, home and laboratory did not differ in the degree to which dream reports could be elicited from 4/5 year old children; (2) the rate of truly spontaneous reporting of dreams at home by 6/7 year olds is so minimal as to render these dreams an unfit base for generalization to typical dream life at these ages; (3) with constant dream sampling procedures, home and laboratory reports were not significantly different in content for 10/11 year olds; (4) results typically observed in uncontrolled home versus laboratory studies are replicable at the child level (ages 12/13), but probably reflect biased recall at home rather than effects of REM-monitoring procedures in the laboratory. The extant literature on home versus laboratory dream differences was reviewed, and it was concluded that even for normative dream studies, the REM-monitoring procedure is the method of choice."}
{"id": "PMID:232568", "title": "The actioculographic monitor of sleep.", "content": "The actioculographic monitor (AOGM) is a newly developed, flexible system for sleep recording using three criteria: eye movements, body movements, and submental electromyogram. The signals are recorded on a four-channel Medilog casette tape and displayed by a mingograph at very low speed. The record is then scored after certain criteria for stages wake, nonrapid eye movement, and rapid eye movement sleep. High statistical correlations were obtained when scoring of the AOGM was compared to scoring of standard polygraphic sleep recordings.", "contents": "The actioculographic monitor of sleep. The actioculographic monitor (AOGM) is a newly developed, flexible system for sleep recording using three criteria: eye movements, body movements, and submental electromyogram. The signals are recorded on a four-channel Medilog casette tape and displayed by a mingograph at very low speed. The record is then scored after certain criteria for stages wake, nonrapid eye movement, and rapid eye movement sleep. High statistical correlations were obtained when scoring of the AOGM was compared to scoring of standard polygraphic sleep recordings."}
{"id": "PMID:232570", "title": "Mitogen-induced differentiation of human CLL lymphocytes to antibody-secreting cells.", "content": "Peripheral blood lymphocytes from nine patients with chronic lymphatic leukaemia (CLL) have been stimulated by photohaemagglutinin, pokeweed mitogen and Epstein-Barr virus. Our results provide proof that the leukaemic B cells in CLL are capable of responding to mitogenic signals by producing and secreting antibodies, transforming into blast cells, and, probably, increasing their rate of DNA synthesis.", "contents": "Mitogen-induced differentiation of human CLL lymphocytes to antibody-secreting cells. Peripheral blood lymphocytes from nine patients with chronic lymphatic leukaemia (CLL) have been stimulated by photohaemagglutinin, pokeweed mitogen and Epstein-Barr virus. Our results provide proof that the leukaemic B cells in CLL are capable of responding to mitogenic signals by producing and secreting antibodies, transforming into blast cells, and, probably, increasing their rate of DNA synthesis."}
{"id": "PMID:232569", "title": "ACTH-adrenal system and exogenous steroids.", "content": "The results obtained from a research on 100 patients of both sexes affected with bronchial asthma, chronic obstructive bronchopathy, rheumatoid arthritis, haematological disorders and some other pathological forms, all depending on steroid therapy, are reported in this paper. The treatment was carried out using a new chronopluricorticoid (Dutimelan 8 15). The clinical efficiency is comparable to that obtained by the traditional steroid treatment with the advantage that symptoms of hypercorticism were absent or insignificant. The authors believe that such excellent results are to be attributed to the particular chronopharmacological characteristics of this preparation.", "contents": "ACTH-adrenal system and exogenous steroids. The results obtained from a research on 100 patients of both sexes affected with bronchial asthma, chronic obstructive bronchopathy, rheumatoid arthritis, haematological disorders and some other pathological forms, all depending on steroid therapy, are reported in this paper. The treatment was carried out using a new chronopluricorticoid (Dutimelan 8 15). The clinical efficiency is comparable to that obtained by the traditional steroid treatment with the advantage that symptoms of hypercorticism were absent or insignificant. The authors believe that such excellent results are to be attributed to the particular chronopharmacological characteristics of this preparation."}
{"id": "PMID:232575", "title": "The preservation of medically important fungi.", "content": "Details are given of a method, first described in 1962, for preservation of fungi in anhydrous silica gel. It is shown that the procedure is suitable for use with dermatophytes, yeasts and other fungi of medical importance and that they may be preserved for periods of 5 years or more.", "contents": "The preservation of medically important fungi. Details are given of a method, first described in 1962, for preservation of fungi in anhydrous silica gel. It is shown that the procedure is suitable for use with dermatophytes, yeasts and other fungi of medical importance and that they may be preserved for periods of 5 years or more."}
{"id": "PMID:232576", "title": "Increased mutation rates in doubly viral transformed Chinese hamster cells.", "content": "An untransformed parental Chinese hamster cell line, one polyoma transformed clone, and two clones containing both SV40 and polyoma DNA were tested for the appearance of variants resistant to 6-thioguanine or oubain. The frequency of such variants was found to be highest in doubly transformed cells. The mutation rate at these loci was correlated with the level of transformation. The mutants observed were stable and had low reversion frequencies with no gross cytogenetic changes. These results establish a quantitative basis  for the evaluation of phenotypic variability observed in transformed cell populations.", "contents": "Increased mutation rates in doubly viral transformed Chinese hamster cells. An untransformed parental Chinese hamster cell line, one polyoma transformed clone, and two clones containing both SV40 and polyoma DNA were tested for the appearance of variants resistant to 6-thioguanine or oubain. The frequency of such variants was found to be highest in doubly transformed cells. The mutation rate at these loci was correlated with the level of transformation. The mutants observed were stable and had low reversion frequencies with no gross cytogenetic changes. These results establish a quantitative basis  for the evaluation of phenotypic variability observed in transformed cell populations."}
{"id": "PMID:232577", "title": "Expression of late viral functions in SV40-infected rat-monkey somatic cell hybrids.", "content": "Somatic cell hybrids between a rat hepatoma cell line and an SV40-transformed African green monkey kidney cell line (T22 TK-) have been isolated and their response to infection by SV40 virus characterized. The parental rat cells are nonpermissive to productive infection by SV40, while the parental monkey cells, which are T-antigen positive and capsid antigen negative, are permissive to productive infection. Hybrid clones, which had segregated monkey chromosomes, were infected with SV40 virus, and some clones were found to be negative for SV40 capsid antigen production while other clones were positive. Capsid antigen-positive clones production while other clones were positive. Capsid antigen-positive clones produced little or no form I SV40 DNA, no infectious virus, and were not capable of rescuing SV40 from SV40-transformed mouse cells. Such hybrids, which produce late viral proteins in the absence of mature progeny viral DNA may be useful in the study of control of SV40 RNA transcription.", "contents": "Expression of late viral functions in SV40-infected rat-monkey somatic cell hybrids. Somatic cell hybrids between a rat hepatoma cell line and an SV40-transformed African green monkey kidney cell line (T22 TK-) have been isolated and their response to infection by SV40 virus characterized. The parental rat cells are nonpermissive to productive infection by SV40, while the parental monkey cells, which are T-antigen positive and capsid antigen negative, are permissive to productive infection. Hybrid clones, which had segregated monkey chromosomes, were infected with SV40 virus, and some clones were found to be negative for SV40 capsid antigen production while other clones were positive. Capsid antigen-positive clones production while other clones were positive. Capsid antigen-positive clones produced little or no form I SV40 DNA, no infectious virus, and were not capable of rescuing SV40 from SV40-transformed mouse cells. Such hybrids, which produce late viral proteins in the absence of mature progeny viral DNA may be useful in the study of control of SV40 RNA transcription."}
{"id": "PMID:232578", "title": "X chromosome inactivaton and SV40 transformation of mammalian cells.", "content": "Five embryonic mouse cultures and one human fibroblast culture were transformed with SV40. The cultures were studied cytologically to see if the normal pattern of sex chromosome replication was maintained in SV40 transformed cells. Characteristic late replication patterns were observed for both the X and Y chromosomes, and there was no evidence for loss of the inactive X chromosome, even in cells with 4 or more X chromosomes. The human line was heterozygous at two X-linked loci and a clonal analysis showed that the expression of X-linked genes was not affected by SV40 transformation.", "contents": "X chromosome inactivaton and SV40 transformation of mammalian cells. Five embryonic mouse cultures and one human fibroblast culture were transformed with SV40. The cultures were studied cytologically to see if the normal pattern of sex chromosome replication was maintained in SV40 transformed cells. Characteristic late replication patterns were observed for both the X and Y chromosomes, and there was no evidence for loss of the inactive X chromosome, even in cells with 4 or more X chromosomes. The human line was heterozygous at two X-linked loci and a clonal analysis showed that the expression of X-linked genes was not affected by SV40 transformation."}
{"id": "PMID:232579", "title": "Studies on cell transformation.", "content": "Seven different transformation stigmata of the transformed CHO cell line, including morphological characteristics, growth behavior, cell membrane biochemical properties, and failure of fibronectin deposition, are reversed by addition of cAMP derivatives to the medium. Simultaneously the microtubular pattern changes from a sparse, relatively random set to an orderly arrangement of tubules largely parallel to each other and to the long axis of the resulting fibroblastic cell. Agents like colcemid and cytochalasin B, respectively disorganizing microtubular and particular microfilamentous structures, prevent at least certain aspects of the reverse transformation reaction induced by cAMP in interphase cells. It is proposed that malignant transformation can be effected by damage to the microtubular and microfilamentous structures which changes cell constitution and behavior in two ways: (1) chromosomal instability is introduced which promotes continuous selection for variants better able to resist environmental signals to limit reproduction and (2) a variety of metabolic defects in biochemical processes such as specific membrane functions are introduced which may alter the growth responses of the cell. This picture offers a reasonable explanation for a number of aspects of normal and malignant cell behavior.", "contents": "Studies on cell transformation. Seven different transformation stigmata of the transformed CHO cell line, including morphological characteristics, growth behavior, cell membrane biochemical properties, and failure of fibronectin deposition, are reversed by addition of cAMP derivatives to the medium. Simultaneously the microtubular pattern changes from a sparse, relatively random set to an orderly arrangement of tubules largely parallel to each other and to the long axis of the resulting fibroblastic cell. Agents like colcemid and cytochalasin B, respectively disorganizing microtubular and particular microfilamentous structures, prevent at least certain aspects of the reverse transformation reaction induced by cAMP in interphase cells. It is proposed that malignant transformation can be effected by damage to the microtubular and microfilamentous structures which changes cell constitution and behavior in two ways: (1) chromosomal instability is introduced which promotes continuous selection for variants better able to resist environmental signals to limit reproduction and (2) a variety of metabolic defects in biochemical processes such as specific membrane functions are introduced which may alter the growth responses of the cell. This picture offers a reasonable explanation for a number of aspects of normal and malignant cell behavior."}
{"id": "PMID:232580", "title": "Biphasic effects of ethanol on behavioral and electrophysiological parameters can be explained by functional organization of neural networks.", "content": "The biphasic effect of ethanol on the CNS is usually explained by assuming that excitatory and depressant effects are mediated by different mechanisms. The present alternative explanation states that ethanol depresses the activity of all neurons to the same extent, but that the biphasic effect can result from the functional organization of the neural network concerned. Current experimental evidence is in accordance with both explanations.", "contents": "Biphasic effects of ethanol on behavioral and electrophysiological parameters can be explained by functional organization of neural networks. The biphasic effect of ethanol on the CNS is usually explained by assuming that excitatory and depressant effects are mediated by different mechanisms. The present alternative explanation states that ethanol depresses the activity of all neurons to the same extent, but that the biphasic effect can result from the functional organization of the neural network concerned. Current experimental evidence is in accordance with both explanations."}
{"id": "PMID:232581", "title": "Oscillatory potentials in the electroretinogram.", "content": "This paper presents an analog circuit model of the electroretinogram b-wave and subsequent oscillations postulated to result from the depolarization of the retinal glial cells produced by potassium. The system is described by a second-order equation which oscillates under conditions of light adaptation. With dark adaptation the oscillations undergo attenuation. Light falling on the retina ultimately liberates potassium ions and this ionic current is considered to be the system input. A first approximation is an exponentially decaying current which varies depending upon light background, flash intensity and various drug manipulations. This model is a reasonable fit to the electroretinogram over considerable light background levels and is suggested as a useful tool in the study of various pharmacological effects on retinal electrophysiology.", "contents": "Oscillatory potentials in the electroretinogram. This paper presents an analog circuit model of the electroretinogram b-wave and subsequent oscillations postulated to result from the depolarization of the retinal glial cells produced by potassium. The system is described by a second-order equation which oscillates under conditions of light adaptation. With dark adaptation the oscillations undergo attenuation. Light falling on the retina ultimately liberates potassium ions and this ionic current is considered to be the system input. A first approximation is an exponentially decaying current which varies depending upon light background, flash intensity and various drug manipulations. This model is a reasonable fit to the electroretinogram over considerable light background levels and is suggested as a useful tool in the study of various pharmacological effects on retinal electrophysiology."}
{"id": "PMID:232584", "title": "Uveitis associated with sarcoidosis and angiotensin converting enzyme.", "content": "Sarcoid uveitis is usually a presumptive diagnosis based on the simultaneous presence of uveitis and clinicoradiographic or histologic findings of sarcoidosis. The elevation of serum ACE in some patients with granulomatous uveitis is strongly presumptive of sarcoid uveitis even in the absence of these findings. Serum ACE may prove to be a useful indicator of ocular sarcoid in the absence of otherwise undetectable systemic disease.", "contents": "Uveitis associated with sarcoidosis and angiotensin converting enzyme. Sarcoid uveitis is usually a presumptive diagnosis based on the simultaneous presence of uveitis and clinicoradiographic or histologic findings of sarcoidosis. The elevation of serum ACE in some patients with granulomatous uveitis is strongly presumptive of sarcoid uveitis even in the absence of these findings. Serum ACE may prove to be a useful indicator of ocular sarcoid in the absence of otherwise undetectable systemic disease."}
{"id": "PMID:232585", "title": "Experimental intraocular malignancy: the effect of intracameral perfusion.", "content": "Transplantable Brown-Pearce carcinoma was adapted successfully in the rabbit anterior chamber. Regression of tumor growth was attained on tri-weekly perfusion of the AC with 10 micromolar of methotrexate. Tumor cyclic nucleotide phosphodiesterase (PDE) and protein activator were found to be markedly depressed during the course of chemotherapy and the PDE cAMP/cGMP ratio was similarly altered. Corroborative light and electron-microscopic studies showed specific alterations of intracellular organelles in relation to MTX and tumor cell death. These findings suggest that metabolic pathways of cyclic nucleotides are important biochemical modulators of neoplastic cells. The method of intraocular perfusion precludes systemic toxic effects and avoids compromising the animals' immunocompetence.", "contents": "Experimental intraocular malignancy: the effect of intracameral perfusion. Transplantable Brown-Pearce carcinoma was adapted successfully in the rabbit anterior chamber. Regression of tumor growth was attained on tri-weekly perfusion of the AC with 10 micromolar of methotrexate. Tumor cyclic nucleotide phosphodiesterase (PDE) and protein activator were found to be markedly depressed during the course of chemotherapy and the PDE cAMP/cGMP ratio was similarly altered. Corroborative light and electron-microscopic studies showed specific alterations of intracellular organelles in relation to MTX and tumor cell death. These findings suggest that metabolic pathways of cyclic nucleotides are important biochemical modulators of neoplastic cells. The method of intraocular perfusion precludes systemic toxic effects and avoids compromising the animals' immunocompetence."}
{"id": "PMID:232586", "title": "[Production and study of the immunogenic properties of a bivalent inactivated vaccine against mucosal disease (bovine viral diarrhea and infectious rhinotracheitis)].", "content": "Bivalent inactivated vaccine against mucous disease (MD) and infectious rhinotracheitis (IR) in cattle was produced from cell cultural MD and IR virus suspensions. The vaccine was concentrated on aluminium hydroxide, inactivated by ethanol and is without residual virus. Saponine in final 1:1500 dilution is added as supplementary adjuvant. Immunogeneity of the vaccine was tested on 10-month-old calves, which had shown full resistance against experimental infection with virulent strains of both viruses. Testing on calves for harmlessness by use of a five-fold higher vaccine dose indicated complete tolerance of the vaccine. The prophylactic effect of the vaccine applied in practical work to directly threatened with immediate MD and IR infection cows, including pregnant ones, consisted in reduced number of cases of abortion, of inborn malformations, in lower neonatal calf death-rate, etc. No disturbances were observed following two-fold vaccination of the animals, a fact proving its harmlessness. The positive results of the studied vaccine allow its further application in the combined prophylaxis of MD and IR in calf fattening and breeding complexes.", "contents": "[Production and study of the immunogenic properties of a bivalent inactivated vaccine against mucosal disease (bovine viral diarrhea and infectious rhinotracheitis)]. Bivalent inactivated vaccine against mucous disease (MD) and infectious rhinotracheitis (IR) in cattle was produced from cell cultural MD and IR virus suspensions. The vaccine was concentrated on aluminium hydroxide, inactivated by ethanol and is without residual virus. Saponine in final 1:1500 dilution is added as supplementary adjuvant. Immunogeneity of the vaccine was tested on 10-month-old calves, which had shown full resistance against experimental infection with virulent strains of both viruses. Testing on calves for harmlessness by use of a five-fold higher vaccine dose indicated complete tolerance of the vaccine. The prophylactic effect of the vaccine applied in practical work to directly threatened with immediate MD and IR infection cows, including pregnant ones, consisted in reduced number of cases of abortion, of inborn malformations, in lower neonatal calf death-rate, etc. No disturbances were observed following two-fold vaccination of the animals, a fact proving its harmlessness. The positive results of the studied vaccine allow its further application in the combined prophylaxis of MD and IR in calf fattening and breeding complexes."}
{"id": "PMID:232587", "title": "[Chronic progressive interstitial pneumonia in sheep (adenovirus pneumonia)].", "content": "Adenoviral infection was established in imported specialized meat strains of sheep Ile de France and Romni marsh. The disease followed a course typical of chronic interstitial progressive pneumonia with reduced tonus, loss of body weight, and high lethality. The disease was serologically proven by the discovery of specific complement binding antibodies in dynamics against the adenovirus. Titers varied from 1 : 2 to 1 : 32. The infestation was reproduced on sheep and lambs by tracheal infection with ultrafiltrate of changed lung tissue and bronchial lymph nodes. Morphologically the infection manifests itself by considerable hypeplastic processes in the lungs and less pronounced ones in the liver and kidneys. The typical changes indicated are accumulation of lymphoid cells and histocytes in the interstitial tissue, as well as adenomatous expansion of alveolar and bronchial epithelium. Considerable cell polymorphism is observed in the alveoles along with presence of gigantic cells and cell syncytia of desquamous epithelial cells, alveolar macrophages and intranuclear inclusions in some of these cells. Complications of Past. Haemolytica with developing catharalsuppurative pneumonia were observed in some cases.", "contents": "[Chronic progressive interstitial pneumonia in sheep (adenovirus pneumonia)]. Adenoviral infection was established in imported specialized meat strains of sheep Ile de France and Romni marsh. The disease followed a course typical of chronic interstitial progressive pneumonia with reduced tonus, loss of body weight, and high lethality. The disease was serologically proven by the discovery of specific complement binding antibodies in dynamics against the adenovirus. Titers varied from 1 : 2 to 1 : 32. The infestation was reproduced on sheep and lambs by tracheal infection with ultrafiltrate of changed lung tissue and bronchial lymph nodes. Morphologically the infection manifests itself by considerable hypeplastic processes in the lungs and less pronounced ones in the liver and kidneys. The typical changes indicated are accumulation of lymphoid cells and histocytes in the interstitial tissue, as well as adenomatous expansion of alveolar and bronchial epithelium. Considerable cell polymorphism is observed in the alveoles along with presence of gigantic cells and cell syncytia of desquamous epithelial cells, alveolar macrophages and intranuclear inclusions in some of these cells. Complications of Past. Haemolytica with developing catharalsuppurative pneumonia were observed in some cases."}
{"id": "PMID:232588", "title": "[Dovenix and Acedist residues in the tissues and organs of guinea pigs and their effects on biochemical blood indices].", "content": "It was established that the antihelminth preparations dovenix and acedist are deposited in all inner organs and muscle tissues of laboratory animals (guinea-pigs) treated once with doses 0.1 cm by injection and 100 mg per os. Residual quantities of the named antihelminth preparations were found on the 6th to 57th day post treatment in the liver, lung, heart, kidneys, spleen and muscles. On the 61st day no residual quantities of the preparations were assessed in the muscles and inner organs. The hematological investigations and proteinogramms of experimental animals treated with dovenix and acedist do not reveal significant changes. In guinea-pigs treated with acedist a certain reduction of the beta- and gamma-globulin fractions is observed, while in those treated with dovenix the beta-globulin fractions are reduced.", "contents": "[Dovenix and Acedist residues in the tissues and organs of guinea pigs and their effects on biochemical blood indices]. It was established that the antihelminth preparations dovenix and acedist are deposited in all inner organs and muscle tissues of laboratory animals (guinea-pigs) treated once with doses 0.1 cm by injection and 100 mg per os. Residual quantities of the named antihelminth preparations were found on the 6th to 57th day post treatment in the liver, lung, heart, kidneys, spleen and muscles. On the 61st day no residual quantities of the preparations were assessed in the muscles and inner organs. The hematological investigations and proteinogramms of experimental animals treated with dovenix and acedist do not reveal significant changes. In guinea-pigs treated with acedist a certain reduction of the beta- and gamma-globulin fractions is observed, while in those treated with dovenix the beta-globulin fractions are reduced."}
{"id": "PMID:232589", "title": "[Resistance of the Aujeszky's disease virus to gamma ray irradiation].", "content": "Investigations on the resistance of Aujeszky's disease virus to gamma irradiation from a 60Co source were performed. The resistance of the virus was tested in vitro in a fluid medium of 50% Henk's balanced saline solution, 50% Eagle's medium MEM and a supplement of 10% normal calf serum as well as its resistance on artificially virus infected pig skin and greasy wool of sheep. It is established that virus inactivation in the fluid medium occurs following 1.6 Mrad gamma irradiation. The irradiated with lower than 1.6 Mrad gamma doses live virus particles form smaller than and with irregular oval shape and dentated plates as compared to the non-irradiated control virus. 1.5 Mrad gamma rays are needed to inactivate the virus on pig skin and greasy wheep's wool. The presence of lanoline in greasy sheep's wool, due to the alkaline pH (9--13) it produces, has an effect on the vitality of the virus both in the control and in the experimental samples.", "contents": "[Resistance of the Aujeszky's disease virus to gamma ray irradiation]. Investigations on the resistance of Aujeszky's disease virus to gamma irradiation from a 60Co source were performed. The resistance of the virus was tested in vitro in a fluid medium of 50% Henk's balanced saline solution, 50% Eagle's medium MEM and a supplement of 10% normal calf serum as well as its resistance on artificially virus infected pig skin and greasy wool of sheep. It is established that virus inactivation in the fluid medium occurs following 1.6 Mrad gamma irradiation. The irradiated with lower than 1.6 Mrad gamma doses live virus particles form smaller than and with irregular oval shape and dentated plates as compared to the non-irradiated control virus. 1.5 Mrad gamma rays are needed to inactivate the virus on pig skin and greasy wheep's wool. The presence of lanoline in greasy sheep's wool, due to the alkaline pH (9--13) it produces, has an effect on the vitality of the virus both in the control and in the experimental samples."}
{"id": "PMID:232591", "title": "Studies on the substrate specificity of the DNA methylase activity from Escherichia coli K-12.", "content": "A partially purified extract of DNA methylases from E. coli K-12 containing DNA-adenine as well as DNA-cytosine methylase activities has been examined with respect to different DNA species as substrates. The results show that the natural content of 6-MAP) in the applied DNA represses the DNA-adenine methylase activity. On the other hand, 5-MC, already present in the substrate does not influence the activity of the DNA-cytosine methylase. DNA from Micrococcus radiodurans, which is completely free of methylated bases served as comparison. Since netropsin preferentially binds to AT-rich regions of DNA, the influence of this oligopeptide antibiotic on the methylation of DNA was investigated. As expected the antibiotic predominantly inhibits adenine methylation of DNA. The degree of inhibition depends on the molar ratio of netropsin to DNA phosphate.", "contents": "Studies on the substrate specificity of the DNA methylase activity from Escherichia coli K-12. A partially purified extract of DNA methylases from E. coli K-12 containing DNA-adenine as well as DNA-cytosine methylase activities has been examined with respect to different DNA species as substrates. The results show that the natural content of 6-MAP) in the applied DNA represses the DNA-adenine methylase activity. On the other hand, 5-MC, already present in the substrate does not influence the activity of the DNA-cytosine methylase. DNA from Micrococcus radiodurans, which is completely free of methylated bases served as comparison. Since netropsin preferentially binds to AT-rich regions of DNA, the influence of this oligopeptide antibiotic on the methylation of DNA was investigated. As expected the antibiotic predominantly inhibits adenine methylation of DNA. The degree of inhibition depends on the molar ratio of netropsin to DNA phosphate."}
{"id": "PMID:232592", "title": "Effects of drugs that influence eucaryotic motile processes on motility of Cystobacter fuscus (Myxobacterales).", "content": "Cytochalasin B, dbcAMP and EGTA were found to inhibit the motility of Cystobacter fuscus completely whereas colchicine and cAMP only reduced velocity of movement.", "contents": "Effects of drugs that influence eucaryotic motile processes on motility of Cystobacter fuscus (Myxobacterales). Cytochalasin B, dbcAMP and EGTA were found to inhibit the motility of Cystobacter fuscus completely whereas colchicine and cAMP only reduced velocity of movement."}
{"id": "PMID:232593", "title": "[Use of gen5 and gen6 ts-mutants of phage T3 as indicators of inhibitors of DNA synthesis].", "content": "In an enzyme-specific drug screening system nalidixic acid and 3'-FTdR, inhibitors of DNA synthesis, both reduce the growth of wild type and temperature-sensitive point mutants of phage T3 with different efficiencies. The wild type shows the strongest sensitivity against the drugs, while an exonuclease mutant is the most insensitive variant. The DNA polymerase mutants exhibit an intermediate degree of inhibition. The anthracycline antibiotics violamycin BI and adriblastin which preferentially inhibit RNA synthesis show the same degree of inhibition for all mutants. This is true also for the RNA synthesis inhibitor lambdamycin, which is identical with chartreusin. The protein synthesis inhibitors chloramphenicol and o-phenanthroline, a chelating agent, impair all mutants to the same extent. Our data confirm the hypothesis that structural variants of essential viral enzymes, when compared with the wild type should reveal different sensitivities against specific inhibitors and show that this T3 system could be used for the indication of specific inhibitors of DNA synthesis.", "contents": "[Use of gen5 and gen6 ts-mutants of phage T3 as indicators of inhibitors of DNA synthesis]. In an enzyme-specific drug screening system nalidixic acid and 3'-FTdR, inhibitors of DNA synthesis, both reduce the growth of wild type and temperature-sensitive point mutants of phage T3 with different efficiencies. The wild type shows the strongest sensitivity against the drugs, while an exonuclease mutant is the most insensitive variant. The DNA polymerase mutants exhibit an intermediate degree of inhibition. The anthracycline antibiotics violamycin BI and adriblastin which preferentially inhibit RNA synthesis show the same degree of inhibition for all mutants. This is true also for the RNA synthesis inhibitor lambdamycin, which is identical with chartreusin. The protein synthesis inhibitors chloramphenicol and o-phenanthroline, a chelating agent, impair all mutants to the same extent. Our data confirm the hypothesis that structural variants of essential viral enzymes, when compared with the wild type should reveal different sensitivities against specific inhibitors and show that this T3 system could be used for the indication of specific inhibitors of DNA synthesis."}
{"id": "PMID:232594", "title": "Corticotroph cells of the human pituitary in old age.", "content": "This study was undertaken, utilizing immunocytologic methods and in particular the immunoperoxidase technique, to evaluate corticotroph cell morphology and distribution in the pituitary glands of aged subjects dying of various diseases. Early histologic studies did not allow for reliable identification of the different adenohypophysial cell types. Corticotroph cell distribution within the gland is described as well as its morphological characteristics. Our findings substantiate conclusions based on biochemical investigations that corticotroph cells remain unchanged and function normally in aged subjects.", "contents": "Corticotroph cells of the human pituitary in old age. This study was undertaken, utilizing immunocytologic methods and in particular the immunoperoxidase technique, to evaluate corticotroph cell morphology and distribution in the pituitary glands of aged subjects dying of various diseases. Early histologic studies did not allow for reliable identification of the different adenohypophysial cell types. Corticotroph cell distribution within the gland is described as well as its morphological characteristics. Our findings substantiate conclusions based on biochemical investigations that corticotroph cells remain unchanged and function normally in aged subjects."}
{"id": "PMID:232595", "title": "Molecular cloning of the restriction fragments derived from double EcoRI/PstI digestion of the calf satellite I DNA and their restriction analysis.", "content": "Calf satellite I DNA digested with EcoRI and PstI gives three fragments 643, 621 and 83 bp long. Two of them, the 643 and 621 bp were cloned using pBR 322 vector and analyzed by means of the MspI and HaeIII restriction enzymes.", "contents": "Molecular cloning of the restriction fragments derived from double EcoRI/PstI digestion of the calf satellite I DNA and their restriction analysis. Calf satellite I DNA digested with EcoRI and PstI gives three fragments 643, 621 and 83 bp long. Two of them, the 643 and 621 bp were cloned using pBR 322 vector and analyzed by means of the MspI and HaeIII restriction enzymes."}
{"id": "PMID:232596", "title": "Expression of aspartokinase, dihydrodipicolinic acid synthase and homoserine dehydrogenase during growth of carrot cell suspension cultures on lysine- and threonine-supplemented media.", "content": "Reduction in the amounts of activity of the first enzyme, aspartokinase (EC 2.7.2.4) and two branch-point enzymes, dihydrodipicolinic acid synthase (EC 4.2.1.52) and homoserine dehydrogenase (EC 1.1.1.3), located in the pathway for the synthesis of aspartate-family amino acids, occurred when cell suspension cultures of Daucus carota L. var. Danvers were grown in media containing 2 mM threonine or 2 mM lysine, endproducts of the pathway. Activity of the lysine-sensitive form of aspartokinase was decreased when cells were grown in medium containing lysine and the activity of the threonine-sensitive form was decreased when cells were grown in medium containing threonine. Activity of the branch-point enzyme leading to threonine synthesis, homoserine dehydrogenase, was decreased up to 70% in specific activity (units/mg protein) and relative activity (units/g fresh weight) when cells were grown in media containing lysine or threonine. Threonine had no effect on the relative activity of dihydrodipicolinic acid synthase, but decreased its specific activity. Lysine decreased the relative activity of the synthase by up to 40%, but had little effect on its specific activity. The decreased activities of the enzymes were apparently not due to binding of the inhibitory amino acids to the enzymes since homogenization of cells in buffer with 2 mM lysine and threonine did not decrease the measurable enzyme activities. These and other results presented suggest that both forms of the aspartokinase activity and homoserine dehydrogenase activity can be altered by supplementing the growth medium with lysine or threonine.", "contents": "Expression of aspartokinase, dihydrodipicolinic acid synthase and homoserine dehydrogenase during growth of carrot cell suspension cultures on lysine- and threonine-supplemented media. Reduction in the amounts of activity of the first enzyme, aspartokinase (EC 2.7.2.4) and two branch-point enzymes, dihydrodipicolinic acid synthase (EC 4.2.1.52) and homoserine dehydrogenase (EC 1.1.1.3), located in the pathway for the synthesis of aspartate-family amino acids, occurred when cell suspension cultures of Daucus carota L. var. Danvers were grown in media containing 2 mM threonine or 2 mM lysine, endproducts of the pathway. Activity of the lysine-sensitive form of aspartokinase was decreased when cells were grown in medium containing lysine and the activity of the threonine-sensitive form was decreased when cells were grown in medium containing threonine. Activity of the branch-point enzyme leading to threonine synthesis, homoserine dehydrogenase, was decreased up to 70% in specific activity (units/mg protein) and relative activity (units/g fresh weight) when cells were grown in media containing lysine or threonine. Threonine had no effect on the relative activity of dihydrodipicolinic acid synthase, but decreased its specific activity. Lysine decreased the relative activity of the synthase by up to 40%, but had little effect on its specific activity. The decreased activities of the enzymes were apparently not due to binding of the inhibitory amino acids to the enzymes since homogenization of cells in buffer with 2 mM lysine and threonine did not decrease the measurable enzyme activities. These and other results presented suggest that both forms of the aspartokinase activity and homoserine dehydrogenase activity can be altered by supplementing the growth medium with lysine or threonine."}
{"id": "PMID:232597", "title": "Permeability of plasma membrane vesicle to ouabain and Mg2+ as a factor determining rate of binding of ouabain to Na+ and K+ dependent ATPase.", "content": "Na+, K+-ATPase of the plasma membrane isolated from sheep kidney medulla exhibits functional asymmetry for the cardiac glycoside ouabain. In this vesicular membrane preparation the rate of binding of ouabain was slow (time constant greater than 60 min) when the vesicles were incubated in the presence of isotonic sucrose. Upon treatment of the preparation with hypoosmotic shock or phospholipase A the initial rate of ouabain binding was enhanced at least 3 fold. In equilibrium a concentration of the ouabain-enzyme-complex was obtained which was about twofold that of the untreated vesicles. This result suggests two types of ouabain binding sites with an approximate stoichiometry of 1 to 1. The stoichiometry seems to be maintained at high concentrations of ouabain where binding curves show a biphasic time course. Additional information about heterogeneity of binding sites comes through experiments in which the vesicles were treated with Mg2+ prior to the addition of ouabain. A minor fraction of the binding sites were occupied by ouabain only after longtime incubation with Mg2+.", "contents": "Permeability of plasma membrane vesicle to ouabain and Mg2+ as a factor determining rate of binding of ouabain to Na+ and K+ dependent ATPase. Na+, K+-ATPase of the plasma membrane isolated from sheep kidney medulla exhibits functional asymmetry for the cardiac glycoside ouabain. In this vesicular membrane preparation the rate of binding of ouabain was slow (time constant greater than 60 min) when the vesicles were incubated in the presence of isotonic sucrose. Upon treatment of the preparation with hypoosmotic shock or phospholipase A the initial rate of ouabain binding was enhanced at least 3 fold. In equilibrium a concentration of the ouabain-enzyme-complex was obtained which was about twofold that of the untreated vesicles. This result suggests two types of ouabain binding sites with an approximate stoichiometry of 1 to 1. The stoichiometry seems to be maintained at high concentrations of ouabain where binding curves show a biphasic time course. Additional information about heterogeneity of binding sites comes through experiments in which the vesicles were treated with Mg2+ prior to the addition of ouabain. A minor fraction of the binding sites were occupied by ouabain only after longtime incubation with Mg2+."}
{"id": "PMID:232598", "title": "II. On the construction of a phylogenetic tree.", "content": "For the construction of a phylogenetic tree in algorithm is described. This, allows the correction of the original data and the proper selection, in each step of the process, of the nearest neighbours of a common ancestor.", "contents": "II. On the construction of a phylogenetic tree. For the construction of a phylogenetic tree in algorithm is described. This, allows the correction of the original data and the proper selection, in each step of the process, of the nearest neighbours of a common ancestor."}
{"id": "PMID:232599", "title": "On the action of diethyldithiocarbamate as inhibitor of copper-zinc superoxide dismutase.", "content": "The rate constants of the reactions between pulse radiolytically produced superoxide radicals and the Cu(II) chelate of diethyldithiocarbamate were determined at pH 7.0. It was found that diethyldithiocarbamate forms a copper complex, which as no dismutating activity. The removal of the protein bound copper in superoxide dismutase by diethyldithiocarbamate yields the same effect as coordination of the copper in the enzyme.", "contents": "On the action of diethyldithiocarbamate as inhibitor of copper-zinc superoxide dismutase. The rate constants of the reactions between pulse radiolytically produced superoxide radicals and the Cu(II) chelate of diethyldithiocarbamate were determined at pH 7.0. It was found that diethyldithiocarbamate forms a copper complex, which as no dismutating activity. The removal of the protein bound copper in superoxide dismutase by diethyldithiocarbamate yields the same effect as coordination of the copper in the enzyme."}
{"id": "PMID:232600", "title": "[Characterization of mitochondria of Aspergillus niger from mycelium growing in surface and submerged culture conditions (author's transl)].", "content": "This paper deals with studies on tightly coupled mitochondria present in the active citric acid producing mycelium of Aspergillus niger growing in surface and submerged culture. A special homogenizer had been used for rapid extraction of mitochondria. Observation in the electron microscope indicated that some of the isolated mitochondria were probably damaged during preparation. Nevertheless, the crude mitochondrial fraction was capable of coupling phosphorylation to the oxidation of three different substrates tested viz., succinate, citrate and NADH. It was found that yield of mitochondria was greater in submerged mycelium than in the surface mycelium of A. niger.", "contents": "[Characterization of mitochondria of Aspergillus niger from mycelium growing in surface and submerged culture conditions (author's transl)]. This paper deals with studies on tightly coupled mitochondria present in the active citric acid producing mycelium of Aspergillus niger growing in surface and submerged culture. A special homogenizer had been used for rapid extraction of mitochondria. Observation in the electron microscope indicated that some of the isolated mitochondria were probably damaged during preparation. Nevertheless, the crude mitochondrial fraction was capable of coupling phosphorylation to the oxidation of three different substrates tested viz., succinate, citrate and NADH. It was found that yield of mitochondria was greater in submerged mycelium than in the surface mycelium of A. niger."}
{"id": "PMID:232602", "title": "[The resistance of a maternally-derived immunity of baby mice against mousepox--experiments regarding a special possibility of immunization with orthopox viruses (author's transl)].", "content": "In the scope of research concerning new proplylactic possibilities against mousepox we tested the resistance of a passive immunity of baby mice whose mothers had been immunized before or during pregnancy several times with either the vaccinia virus strains MVA, CVB or the so-called attenuated ectromelia virus strain \"Hampstead\" respectively. The vaccines CVB and \"Hampstead\" were found to cause the production of haemagglutination-inhibiting antibodies only. A passively-transmitted immunity of baby mice was proven to be effective against an intraperitoneal challenge-infection with a virulent ectromelia virus strain for as long a period as 3 weeks after birth, if their mothers had been vaccinated with either of the following: 10(2,0) and 10(4,0) KID50 of the \"Hampstead\" strain, or one of the vaccinia virus strains in a dosage 100-times as large. The vaccination did not lead to an intrauterine infection of the fetuses. After 224 tissue culture passages in mouse fibroblast cells (line 3T6), THE \"Hampstead\" strain was found te be still virulent for baby mice; however, female adult mice which had been intraperitoneally inoculated with 10(2,0) and then 10(4,0) KID50 two weeks later demonstrated no signs of mousepox. The possibility for using this ectromelia virus strain instead of vaccinia virus for active immunization against mousepox of young animals under the protection of a homologous passive immunity is discussed.", "contents": "[The resistance of a maternally-derived immunity of baby mice against mousepox--experiments regarding a special possibility of immunization with orthopox viruses (author's transl)]. In the scope of research concerning new proplylactic possibilities against mousepox we tested the resistance of a passive immunity of baby mice whose mothers had been immunized before or during pregnancy several times with either the vaccinia virus strains MVA, CVB or the so-called attenuated ectromelia virus strain \"Hampstead\" respectively. The vaccines CVB and \"Hampstead\" were found to cause the production of haemagglutination-inhibiting antibodies only. A passively-transmitted immunity of baby mice was proven to be effective against an intraperitoneal challenge-infection with a virulent ectromelia virus strain for as long a period as 3 weeks after birth, if their mothers had been vaccinated with either of the following: 10(2,0) and 10(4,0) KID50 of the \"Hampstead\" strain, or one of the vaccinia virus strains in a dosage 100-times as large. The vaccination did not lead to an intrauterine infection of the fetuses. After 224 tissue culture passages in mouse fibroblast cells (line 3T6), THE \"Hampstead\" strain was found te be still virulent for baby mice; however, female adult mice which had been intraperitoneally inoculated with 10(2,0) and then 10(4,0) KID50 two weeks later demonstrated no signs of mousepox. The possibility for using this ectromelia virus strain instead of vaccinia virus for active immunization against mousepox of young animals under the protection of a homologous passive immunity is discussed."}
{"id": "PMID:232604", "title": "[Sleep stages and growth hormone in manganese poisoning. Effects of L dopa].", "content": "Sleep characteristics are studied in 7 patients with sequelae of manganese intoxication and in 8 controls. A reduction in the length of the REM stage was observed, which could be prolonged by L Dopa administration, but without achieving values comparable to the controls. No changes were noted in the non-REM stage of sleep. These results are similar to the ones obtained in Parkinson's disease, suggesting clinical and probably biochemical similarities between the 2 conditions. The blood concentrations of growth hormone during sleep in the manganic patients was lower than in the control group, and no significant variations were noted after L Dopa administration.", "contents": "[Sleep stages and growth hormone in manganese poisoning. Effects of L dopa]. Sleep characteristics are studied in 7 patients with sequelae of manganese intoxication and in 8 controls. A reduction in the length of the REM stage was observed, which could be prolonged by L Dopa administration, but without achieving values comparable to the controls. No changes were noted in the non-REM stage of sleep. These results are similar to the ones obtained in Parkinson's disease, suggesting clinical and probably biochemical similarities between the 2 conditions. The blood concentrations of growth hormone during sleep in the manganic patients was lower than in the control group, and no significant variations were noted after L Dopa administration."}
{"id": "PMID:232605", "title": "Cerebral embolism in nonbacterial thrombotic endocarditis associated with carcinoma. A clinico-pathological study.", "content": "The clinical and pathological features of 24 patients with cerebral emboli complicating 66% of our cases of nonbacterial thrombotic endocarditis (NBTE) associated with carcinoma are reviewed. Twelve patients were admitted for a cerebrovascular accident (CVA) while 4 patients developed a CVA during hospitalization. Transient ischemic attacks preceded the CVA in 3 patients. More often the CVA took the form of a single sudden accident. Cerebral infarcts however were generally multiple and hemorrhagic and varied in size and age. In 4 patients large softenings were directly responsible for death. 8.6% of cerebral embolisms were caused by NBTE and in 10 patients cerebral embolization was the first symptom of a carcinoma. The frequency of NBTE in ovarian carcinoma even in the absence of metastases may motivate a more aggressive approach towards unexplained cerebral embolism.", "contents": "Cerebral embolism in nonbacterial thrombotic endocarditis associated with carcinoma. A clinico-pathological study. The clinical and pathological features of 24 patients with cerebral emboli complicating 66% of our cases of nonbacterial thrombotic endocarditis (NBTE) associated with carcinoma are reviewed. Twelve patients were admitted for a cerebrovascular accident (CVA) while 4 patients developed a CVA during hospitalization. Transient ischemic attacks preceded the CVA in 3 patients. More often the CVA took the form of a single sudden accident. Cerebral infarcts however were generally multiple and hemorrhagic and varied in size and age. In 4 patients large softenings were directly responsible for death. 8.6% of cerebral embolisms were caused by NBTE and in 10 patients cerebral embolization was the first symptom of a carcinoma. The frequency of NBTE in ovarian carcinoma even in the absence of metastases may motivate a more aggressive approach towards unexplained cerebral embolism."}
{"id": "PMID:232606", "title": "Chorioretinitis of the newborn with herpes simplex virus type 1. Report of a case.", "content": "A disseminated herpes simplex virus (HSV) infection involving the central nervous system and accompanied by chrioretinitis in a a 3-week-old girl is described. The aetiologic diagnosis was established on the basis of vrius isolated from skin vesicles, and a significant rise in complement fixing antibodies to HSV type 1. The mode of transmission of the virus to the infant apparently was direct contact with an oral lesion in the mother, that was present at the time of delivery. The patient survived but became blind and microcephalic, with severe neurological sequelae. The virus isolated was identified as HSV type 1, which is an infrequent finding in herpetic chorioretinitis of the newborn.", "contents": "Chorioretinitis of the newborn with herpes simplex virus type 1. Report of a case. A disseminated herpes simplex virus (HSV) infection involving the central nervous system and accompanied by chrioretinitis in a a 3-week-old girl is described. The aetiologic diagnosis was established on the basis of vrius isolated from skin vesicles, and a significant rise in complement fixing antibodies to HSV type 1. The mode of transmission of the virus to the infant apparently was direct contact with an oral lesion in the mother, that was present at the time of delivery. The patient survived but became blind and microcephalic, with severe neurological sequelae. The virus isolated was identified as HSV type 1, which is an infrequent finding in herpetic chorioretinitis of the newborn."}
{"id": "PMID:232607", "title": "In vitro production of steroid cataract in bovine lens. Part II: measurement of sodium-potassium adenosine triphosphatase activity.", "content": "Fresh calf lesnses incubated in nutritive media containing dexamethasone phosphate or ouabain in concentrations ranging from 1 X 10(-4) M to 1 X 10(-8) M developed cortical opacification and showed significant inhibition of Na(+)-K(+) ATP'ase activity. Over a 3-day incubation period the decrease in Na+-K+ ATP'ase activity correlated well with the observed decrease in light transmission. The degree of enzyme inhibition and decrease in light transmission varied directly with the concentration of dexamethasone phosphate and ouabain, with significant changes observed at 'physiologic' and 'pharmacologic' concentrations of these agents. Lenses incubated for 4 days in dexamethasone phosphate or ouabain showed substantial increases in water content as well as an increase in Na+ and a decrease in K+ concentration. These data suggest that inhibition of the cation pump may play a significant role in the formation of steroid cataract in vitro.", "contents": "In vitro production of steroid cataract in bovine lens. Part II: measurement of sodium-potassium adenosine triphosphatase activity. Fresh calf lesnses incubated in nutritive media containing dexamethasone phosphate or ouabain in concentrations ranging from 1 X 10(-4) M to 1 X 10(-8) M developed cortical opacification and showed significant inhibition of Na(+)-K(+) ATP'ase activity. Over a 3-day incubation period the decrease in Na+-K+ ATP'ase activity correlated well with the observed decrease in light transmission. The degree of enzyme inhibition and decrease in light transmission varied directly with the concentration of dexamethasone phosphate and ouabain, with significant changes observed at 'physiologic' and 'pharmacologic' concentrations of these agents. Lenses incubated for 4 days in dexamethasone phosphate or ouabain showed substantial increases in water content as well as an increase in Na+ and a decrease in K+ concentration. These data suggest that inhibition of the cation pump may play a significant role in the formation of steroid cataract in vitro."}
{"id": "PMID:232611", "title": "Effect of starvation on tissue and serum gluconeogenic enzymes, alkaline phosphatase and tissue glycogen in the freshwater catfish, Heteropneustes fossilis (Bloch).", "content": "The influence of starvation has been studied on tissue and serum G-6Pase F-D-Pase and alkaline phosphatase activities and on the muscle and liver glycogen content of the freshwater catfish H. fossilis (Bloch). A marked increase in G-6Pase and F-D-Pase activities and a fall in the muscle and liver glycogen content recorded during 40 day starvation. The rise in gluconeogenic enzymes during starvation may be due to glucocorticoid stimulation. Alkaline phosphatase activity was found to decline markedly during starvation. The decline in enzyme activity is attributed to some factors like a fall in the rate of synthesis caused by lowered metabolic demands and to electrolyte imbalance caused by tissue overhydration. The fall in glycogen content may be related to the starved condition of the fish. Elevation in glycogen content and alkaline phosphatase activity and a fall in gluconeogenic enzymes were noted when feeding had been resumed.", "contents": "Effect of starvation on tissue and serum gluconeogenic enzymes, alkaline phosphatase and tissue glycogen in the freshwater catfish, Heteropneustes fossilis (Bloch). The influence of starvation has been studied on tissue and serum G-6Pase F-D-Pase and alkaline phosphatase activities and on the muscle and liver glycogen content of the freshwater catfish H. fossilis (Bloch). A marked increase in G-6Pase and F-D-Pase activities and a fall in the muscle and liver glycogen content recorded during 40 day starvation. The rise in gluconeogenic enzymes during starvation may be due to glucocorticoid stimulation. Alkaline phosphatase activity was found to decline markedly during starvation. The decline in enzyme activity is attributed to some factors like a fall in the rate of synthesis caused by lowered metabolic demands and to electrolyte imbalance caused by tissue overhydration. The fall in glycogen content may be related to the starved condition of the fish. Elevation in glycogen content and alkaline phosphatase activity and a fall in gluconeogenic enzymes were noted when feeding had been resumed."}
{"id": "PMID:232612", "title": "Micro-arousals during nocturnal sleep.", "content": "In 8 young adult human subjects EEG- and polygraphic characteristics of transient shifts towards arousal (micro-arousal, MA) have been studied during sleep under five different experimental conditions in 40 night sessions. Out of the five applied experimental situations, two (psychostimulant application and sensory stimulation) resulted in a shift of the balance between the systems of sleep and arousal towards an increased activity of the arousal system, while an other condition (rebound following partial sleep deprivation) led to an opposite change to a rise in \"sleep pressure\". An inverse correlation has been found between the frequency of MA and the depth of sleep, a finding consistently observed in every subject and in every experimental situation. During the process of sleep periodic changes in the dispersity of MA could be seen; the number of MA-s decreased and increased according to the descending and ascending slope of the sleep cycles. During the ascending slope of cycles there was a coupling between the occurence of MA-s and the changes of phases. Increases in the level of activation and in sleep pressure did not influence the occurrence of MA-s. Increasing the tone of the arousal system in chemical way, or by means of enhancing the phasic sensory input resulted in a reduction of the difference between the number of MA on the descending and ascending slopes of cycles. During the phases of sleep, the spontaneous occurrence of MA-s went parallel with the possibility to evoke MA-s by sensory stimuli. These data show that MA is a regular phenomenon of nocturnal sleep; MA manifests itself as a result of phasic functioning of the reticular arousal system and plays a role in the organization of those periods of the sleep cycle, which tend toward arousal. It is suggested that MA-phenomenon is considered a standard measure of sleep and that it could represent an indicator of the function of the arousal system controlled by external or internal mechanisms during sleep.", "contents": "Micro-arousals during nocturnal sleep. In 8 young adult human subjects EEG- and polygraphic characteristics of transient shifts towards arousal (micro-arousal, MA) have been studied during sleep under five different experimental conditions in 40 night sessions. Out of the five applied experimental situations, two (psychostimulant application and sensory stimulation) resulted in a shift of the balance between the systems of sleep and arousal towards an increased activity of the arousal system, while an other condition (rebound following partial sleep deprivation) led to an opposite change to a rise in \"sleep pressure\". An inverse correlation has been found between the frequency of MA and the depth of sleep, a finding consistently observed in every subject and in every experimental situation. During the process of sleep periodic changes in the dispersity of MA could be seen; the number of MA-s decreased and increased according to the descending and ascending slope of the sleep cycles. During the ascending slope of cycles there was a coupling between the occurence of MA-s and the changes of phases. Increases in the level of activation and in sleep pressure did not influence the occurrence of MA-s. Increasing the tone of the arousal system in chemical way, or by means of enhancing the phasic sensory input resulted in a reduction of the difference between the number of MA on the descending and ascending slopes of cycles. During the phases of sleep, the spontaneous occurrence of MA-s went parallel with the possibility to evoke MA-s by sensory stimuli. These data show that MA is a regular phenomenon of nocturnal sleep; MA manifests itself as a result of phasic functioning of the reticular arousal system and plays a role in the organization of those periods of the sleep cycle, which tend toward arousal. It is suggested that MA-phenomenon is considered a standard measure of sleep and that it could represent an indicator of the function of the arousal system controlled by external or internal mechanisms during sleep."}
{"id": "PMID:232613", "title": "Effect on renal function and renin secretion of noradrenaline infused into the renal artery.", "content": "Effect of noradrenaline on renal function and renin secretion was studied during infusion into the renal artery of anaesthetized dogs. Experiments were performed with or without alpha or beta receptor blockade. Noradrenaline infusion resulted in a significant elevation of renin secretion associated with marked vasoconstriction. Urine flow rate, the filtered and excreted amounts of sodium were diminished due to the decreased GFR. Alpha receptor blockade suppressed renin secretion in the presence of changes in renal haemodynamics. The simultaneous infusion of noradrenaline enhanced renin release without affecting renal haemodynamics or reducing Na-excretion. Following simultaneous inhibition of alpha and beta receptors renin secretion dropped markedly; there were no further changes in either renin secretion or renal haemodynamics upon the simultaneous administration of noradrenaline. Based on the present findings it is suggested that renin secretion is controlled by both alpha and beta receptors. Beta receptor simulation exerts a direct action, whereas alpha stimulation appears to be mediated in part by indirect mechanisms such as renal haemodynamics.", "contents": "Effect on renal function and renin secretion of noradrenaline infused into the renal artery. Effect of noradrenaline on renal function and renin secretion was studied during infusion into the renal artery of anaesthetized dogs. Experiments were performed with or without alpha or beta receptor blockade. Noradrenaline infusion resulted in a significant elevation of renin secretion associated with marked vasoconstriction. Urine flow rate, the filtered and excreted amounts of sodium were diminished due to the decreased GFR. Alpha receptor blockade suppressed renin secretion in the presence of changes in renal haemodynamics. The simultaneous infusion of noradrenaline enhanced renin release without affecting renal haemodynamics or reducing Na-excretion. Following simultaneous inhibition of alpha and beta receptors renin secretion dropped markedly; there were no further changes in either renin secretion or renal haemodynamics upon the simultaneous administration of noradrenaline. Based on the present findings it is suggested that renin secretion is controlled by both alpha and beta receptors. Beta receptor simulation exerts a direct action, whereas alpha stimulation appears to be mediated in part by indirect mechanisms such as renal haemodynamics."}
{"id": "PMID:232617", "title": "Effect of KCN on the motility of Treponema pallidium.", "content": "Virulent Treponema pallidum has been shown to survive in KCN-containing artificial medium. Oxygen uptake being sensitive to cyanide, the observation indicates that treponemes do not have a cytochrome oxidase system. KCN had a killing effect only at a 15--30 mM final concentration. The data show that the Budapest strain of T. pallidum is an anaerobic organism.", "contents": "Effect of KCN on the motility of Treponema pallidium. Virulent Treponema pallidum has been shown to survive in KCN-containing artificial medium. Oxygen uptake being sensitive to cyanide, the observation indicates that treponemes do not have a cytochrome oxidase system. KCN had a killing effect only at a 15--30 mM final concentration. The data show that the Budapest strain of T. pallidum is an anaerobic organism."}
{"id": "PMID:232622", "title": "Functional heterogeneity and T cell-dependent activation of macrophages from murine sarcoma virus (MSV)-induced tumors.", "content": "In studies on the functional activity of macrophages isolated from murine sarcoma virus (MSV)-induced tumors, we have found that these cells may suppress immune responses as well as act as effector cells against the tumor. Previously, we reported that macrophages from the tumor could inhibit the antitumor response by suppressing proliferation-dependent immune functions. Here, we demonstrate that macrophages can also suppress the production of migration inhibition factor (MIF) and macrophage activation factor (MAF), two lymphocyte activities that are independent of cell proliferation. Conversely, we and others have found that macrophages from the tumor can exert an antitumor, cytolytic effect. In this study, using 1 g velocity sedimentation separation techniques, we have been able to identify 2-3 subpopulations of cytolytic macrophages in regressing tumors but in progressing tumors, only the smallest subpopulation of macrophages was active. T cells appeared to be required for activation of macrophages within the tumor, since MSV tumors induced in athymic, nude mice did not contain cytolytic macrophages.", "contents": "Functional heterogeneity and T cell-dependent activation of macrophages from murine sarcoma virus (MSV)-induced tumors. In studies on the functional activity of macrophages isolated from murine sarcoma virus (MSV)-induced tumors, we have found that these cells may suppress immune responses as well as act as effector cells against the tumor. Previously, we reported that macrophages from the tumor could inhibit the antitumor response by suppressing proliferation-dependent immune functions. Here, we demonstrate that macrophages can also suppress the production of migration inhibition factor (MIF) and macrophage activation factor (MAF), two lymphocyte activities that are independent of cell proliferation. Conversely, we and others have found that macrophages from the tumor can exert an antitumor, cytolytic effect. In this study, using 1 g velocity sedimentation separation techniques, we have been able to identify 2-3 subpopulations of cytolytic macrophages in regressing tumors but in progressing tumors, only the smallest subpopulation of macrophages was active. T cells appeared to be required for activation of macrophages within the tumor, since MSV tumors induced in athymic, nude mice did not contain cytolytic macrophages."}
{"id": "PMID:232623", "title": "Mechanism of resistance of mice to syngeneic methylcholanthrene induced fibrosarcomas.", "content": "Mice become resistant to challenge with certain fibrosarcomas when bearing a tumor graft (concomitant immunity) or after injection of a low, non-tumorigenic dose of cells (sinecomitant immunity). Resistance to footpad challenge was depressed or abolished by treatment with carrageenan, niridazole or reserpine, or by sublethal irradiation, all of which also depressed delayed-type hypersensitivity (DTH) reactions. Immune lymphocytes initiating tumor-suppressive reactions in the feet of non-immune mice were Thy-1+, Ly-1+, Ly-2- and Ly-3-. Injection of tumor cells into the peritoneal cavities of immune mice specifically elicited an influx of macrophages. There was evidence of macrophage stimulation in tumor-immune mice. In vitro, anti-tumor effector cells lacking individual tumor specificity could be detected among the resident peritoneal cells of tumor-immune mice and among peritoneal exudate cells of non-immune mice. The expression of acquired resistance to some tumors may involve reactions akin to DTH in which a specific reaction triggers an accumulation of nonspecific effectors.", "contents": "Mechanism of resistance of mice to syngeneic methylcholanthrene induced fibrosarcomas. Mice become resistant to challenge with certain fibrosarcomas when bearing a tumor graft (concomitant immunity) or after injection of a low, non-tumorigenic dose of cells (sinecomitant immunity). Resistance to footpad challenge was depressed or abolished by treatment with carrageenan, niridazole or reserpine, or by sublethal irradiation, all of which also depressed delayed-type hypersensitivity (DTH) reactions. Immune lymphocytes initiating tumor-suppressive reactions in the feet of non-immune mice were Thy-1+, Ly-1+, Ly-2- and Ly-3-. Injection of tumor cells into the peritoneal cavities of immune mice specifically elicited an influx of macrophages. There was evidence of macrophage stimulation in tumor-immune mice. In vitro, anti-tumor effector cells lacking individual tumor specificity could be detected among the resident peritoneal cells of tumor-immune mice and among peritoneal exudate cells of non-immune mice. The expression of acquired resistance to some tumors may involve reactions akin to DTH in which a specific reaction triggers an accumulation of nonspecific effectors."}
{"id": "PMID:232641", "title": "Human placental adenosine kinase: purification and characterization.", "content": "Human placental adenosine kinase has thus been purified 3600-fold and characterized with respect to molecular weight, substrate specificity, divalent cation requirements, pH optimum, isoelectric pH, and kinetic properties. These data contribute to the information currently available about the regulation of adenosine metabolism, information critical for an understanding of the biological properties of adenosine.", "contents": "Human placental adenosine kinase: purification and characterization. Human placental adenosine kinase has thus been purified 3600-fold and characterized with respect to molecular weight, substrate specificity, divalent cation requirements, pH optimum, isoelectric pH, and kinetic properties. These data contribute to the information currently available about the regulation of adenosine metabolism, information critical for an understanding of the biological properties of adenosine."}
{"id": "PMID:232646", "title": "The use of amniotic membrane in acute massive full-thickness loss of the abdominal wall from clostridial myonecrosis.", "content": "A patient who developed clostridial infection of the abdominal wall following laparotomy for small bowel perforation is described. Immediate debridement resulted in the loss of the entire abdominal wall. Dressing of the exposed viscera during the period of stabilization and prior to reconstruction was achieved using amniotic membranes.", "contents": "The use of amniotic membrane in acute massive full-thickness loss of the abdominal wall from clostridial myonecrosis. A patient who developed clostridial infection of the abdominal wall following laparotomy for small bowel perforation is described. Immediate debridement resulted in the loss of the entire abdominal wall. Dressing of the exposed viscera during the period of stabilization and prior to reconstruction was achieved using amniotic membranes."}
{"id": "PMID:232650", "title": "[Study of the effectiveness of morantel tartrate (Exhelm II) in bovine gastrointestinal strongylosis in Ivory Coast].", "content": "A study of the seasonal incidence of the strongyles of the bovine digestive tract, under natural climatic conditions (rainfall, humidity and temperature) and the use of Morantel Tartrate (Exhelm II, Pfizer, France) for its control was conducted, in the North of the Ivory Coast during 1976-1977. Young calves belonging to the local breeds Baoul\u00e9, N'Dama, and cross bred Zebus-taurins employed for this study were located in the East, West, North and Centre of the Korhogo area. On the basis of the results obtained it could be concluded that: the infestation rate calculated on the basis of egg output, increases during the rainy season, between April and October and decreases during the dry season namely between November and March/April; the animals treated twice or three times with Exhelm II expelled considerably less E.P.G., in comparison to that of the control group. It is suggested that this drug may be used at the dosage rate of 7,5 mg per kg live body weight under field condition at least twice in a year, at the beginning and at the end of the rainy season. A third treatment using this same anthelmintic during the rainy season does not seem to be more profitable than two treatments. As such this third treatment should not however be considered as being essential. N'Dama and Baoule of that region have mixt infection of strongyles comprising of Trichchostrongylus 38%, Oesophastomum 30%, Cooperia 17%, Bunostomum 16%, Haemonchus 15%, Hematodirus 2% and Ostertagia 0,2%.", "contents": "[Study of the effectiveness of morantel tartrate (Exhelm II) in bovine gastrointestinal strongylosis in Ivory Coast]. A study of the seasonal incidence of the strongyles of the bovine digestive tract, under natural climatic conditions (rainfall, humidity and temperature) and the use of Morantel Tartrate (Exhelm II, Pfizer, France) for its control was conducted, in the North of the Ivory Coast during 1976-1977. Young calves belonging to the local breeds Baoul\u00e9, N'Dama, and cross bred Zebus-taurins employed for this study were located in the East, West, North and Centre of the Korhogo area. On the basis of the results obtained it could be concluded that: the infestation rate calculated on the basis of egg output, increases during the rainy season, between April and October and decreases during the dry season namely between November and March/April; the animals treated twice or three times with Exhelm II expelled considerably less E.P.G., in comparison to that of the control group. It is suggested that this drug may be used at the dosage rate of 7,5 mg per kg live body weight under field condition at least twice in a year, at the beginning and at the end of the rainy season. A third treatment using this same anthelmintic during the rainy season does not seem to be more profitable than two treatments. As such this third treatment should not however be considered as being essential. N'Dama and Baoule of that region have mixt infection of strongyles comprising of Trichchostrongylus 38%, Oesophastomum 30%, Cooperia 17%, Bunostomum 16%, Haemonchus 15%, Hematodirus 2% and Ostertagia 0,2%."}
{"id": "PMID:232653", "title": "Response of susceptible versus immune chicks to killed, live-modified, and wild infectious bursal disease virus vaccines.", "content": "Modified infectious bursal disease virus (IBDV) administered ocularly to either susceptible or passively immune chicks did not induce protection against bursal atrophy by wild IBDV, while intramuscular (IM) or intrabursal (IB) injection protected susceptible chickens. No protection was obtained in passively immune chickens vaccinated IM or IB. Susceptible and passively immune chickens vaccinated with a single dose of killed-virus suspension (KVS) did not become resistant to wild IBDV challenge. A killed-virus multiple emulsion (KVME) induced partial protection (3/5) against challenge 28 days after subcutaneous vaccination of three-day-old susceptible chickens. At 35 and 42 days old, all susceptible chickens were protected by KVME. Protection by passive antibodies was observed in unvaccinated, KVS-, and KVME-vaccinated chickens challenged at 10 and 17 days of age. Protection was only partial in passively immune chickens vaccinated with KVME after passive antibodies were no longer protective to unvaccinated and KVS-vaccinated chicks. Modified IBDV was detected two days post-IB inoculation only in the bursa of Fabricius of susceptible chickens, while wild IBDV was found also in the thymus, spleen, and blood. No evidence of virus was found in immune chickens inoculated IB with modified IBDV. The growth of wild IBDV was limited to the bursa of Fabricius in immune chickens. Furthermore, the intensity of fluorescence, as well as the number of positive bursa cells, was low when compared with fluorescence in the bursa of susceptible chickens infected with wild IBDV.", "contents": "Response of susceptible versus immune chicks to killed, live-modified, and wild infectious bursal disease virus vaccines. Modified infectious bursal disease virus (IBDV) administered ocularly to either susceptible or passively immune chicks did not induce protection against bursal atrophy by wild IBDV, while intramuscular (IM) or intrabursal (IB) injection protected susceptible chickens. No protection was obtained in passively immune chickens vaccinated IM or IB. Susceptible and passively immune chickens vaccinated with a single dose of killed-virus suspension (KVS) did not become resistant to wild IBDV challenge. A killed-virus multiple emulsion (KVME) induced partial protection (3/5) against challenge 28 days after subcutaneous vaccination of three-day-old susceptible chickens. At 35 and 42 days old, all susceptible chickens were protected by KVME. Protection by passive antibodies was observed in unvaccinated, KVS-, and KVME-vaccinated chickens challenged at 10 and 17 days of age. Protection was only partial in passively immune chickens vaccinated with KVME after passive antibodies were no longer protective to unvaccinated and KVS-vaccinated chicks. Modified IBDV was detected two days post-IB inoculation only in the bursa of Fabricius of susceptible chickens, while wild IBDV was found also in the thymus, spleen, and blood. No evidence of virus was found in immune chickens inoculated IB with modified IBDV. The growth of wild IBDV was limited to the bursa of Fabricius in immune chickens. Furthermore, the intensity of fluorescence, as well as the number of positive bursa cells, was low when compared with fluorescence in the bursa of susceptible chickens infected with wild IBDV."}
{"id": "PMID:232655", "title": "The prevention of experimentally induced necrotic enteritis in chickens by avoparcin.", "content": "Four groups of about seventy 2-week-old broiler chickens were challenged with a Clostridium perfringens Type A isolate. Inclusion of avoparcin at 20 ppm in feed prevented necrotic enteritis in one group, but 10 ppm was only marginally effective. Bacitracin at 110 ppm also prevented the disease. Necrotic enteritis was successfully reproduced in untreated control birds.", "contents": "The prevention of experimentally induced necrotic enteritis in chickens by avoparcin. Four groups of about seventy 2-week-old broiler chickens were challenged with a Clostridium perfringens Type A isolate. Inclusion of avoparcin at 20 ppm in feed prevented necrotic enteritis in one group, but 10 ppm was only marginally effective. Bacitracin at 110 ppm also prevented the disease. Necrotic enteritis was successfully reproduced in untreated control birds."}
{"id": "PMID:232656", "title": "Marek's disease tumor-associated surface antigen (MATSA) in resistant versus susceptible chickens.", "content": "The appearance of MATSA-bearing cells in the spleens of genetically susceptible (P-line) and resistant (N-line) chickens followed similar patterns at 4 and 6 days postinoculation (PI), with 4 to 10% of the cells positive in indirect fluorescent-antibody tests. Levels of MATSA-positive cells at 10, 14, and 21 days PI continued at 6-8% in P-line birds but dropped from about 8% to below 1 or 2% in N-line birds. This pattern was seen also in virus-isolation rates from the same spleen samples. Viral internal antigens (VIA) were seen equally and with decreasing incidence in both groups at 4-10 days PI. VIA were not detected at 14 days but reappeared at 21 days, with higher levels in P-lines than inN-lines. It was concluded that genetic resistance to Marek's disease is not related to events which result in production of the putative tumor antigen, MATSA, but rather to host-controlled factors which terminate those events.", "contents": "Marek's disease tumor-associated surface antigen (MATSA) in resistant versus susceptible chickens. The appearance of MATSA-bearing cells in the spleens of genetically susceptible (P-line) and resistant (N-line) chickens followed similar patterns at 4 and 6 days postinoculation (PI), with 4 to 10% of the cells positive in indirect fluorescent-antibody tests. Levels of MATSA-positive cells at 10, 14, and 21 days PI continued at 6-8% in P-line birds but dropped from about 8% to below 1 or 2% in N-line birds. This pattern was seen also in virus-isolation rates from the same spleen samples. Viral internal antigens (VIA) were seen equally and with decreasing incidence in both groups at 4-10 days PI. VIA were not detected at 14 days but reappeared at 21 days, with higher levels in P-lines than inN-lines. It was concluded that genetic resistance to Marek's disease is not related to events which result in production of the putative tumor antigen, MATSA, but rather to host-controlled factors which terminate those events."}
{"id": "PMID:232657", "title": "Loss of cell-associated Marek's disease vaccine titer during thawing, reconstitution, and use.", "content": "Tests of the effects of mismanagement practices observed in hatcheries showed that very subtle deviations from the explicit directions accompanying Marek's vaccine can cause dramatic losses of vaccine potency. Such mismanagement was found to result in 14 to 97% loss of vaccine titer. It appears that procedures used in hatcheries for the handling of cell-associated Marek's vaccine should be closely monitored on a continuous basis to prevent a gradual drift from correct handling.", "contents": "Loss of cell-associated Marek's disease vaccine titer during thawing, reconstitution, and use. Tests of the effects of mismanagement practices observed in hatcheries showed that very subtle deviations from the explicit directions accompanying Marek's vaccine can cause dramatic losses of vaccine potency. Such mismanagement was found to result in 14 to 97% loss of vaccine titer. It appears that procedures used in hatcheries for the handling of cell-associated Marek's vaccine should be closely monitored on a continuous basis to prevent a gradual drift from correct handling."}
{"id": "PMID:232658", "title": "Characterization of avian reoviruses isolated from the synovia and breast blister.", "content": "Reoviruses Texas, S 1133, UMI 203, and WVU 2937 induced swelling of the foot pad and inflammatory changes in the synovial membranes when inoculated in the foot pad of 2-week-old gnotobiotic chicks. From differences in virus neutralization as measured with geometric mean (R) value, all four viruses are subtypes of a single serotype. The cell-associated and cell-released virus growth curves were similar, with a lag phase of about 15 hours and a log phase of 15 to 21 hours. Viral RNA synthesis reached a peak in 5 hours and was active at 14 hours but not at 18 hours. In 90 minutes at 60 C the titer of each virus had decreased about 4 logs.", "contents": "Characterization of avian reoviruses isolated from the synovia and breast blister. Reoviruses Texas, S 1133, UMI 203, and WVU 2937 induced swelling of the foot pad and inflammatory changes in the synovial membranes when inoculated in the foot pad of 2-week-old gnotobiotic chicks. From differences in virus neutralization as measured with geometric mean (R) value, all four viruses are subtypes of a single serotype. The cell-associated and cell-released virus growth curves were similar, with a lag phase of about 15 hours and a log phase of 15 to 21 hours. Viral RNA synthesis reached a peak in 5 hours and was active at 14 hours but not at 18 hours. In 90 minutes at 60 C the titer of each virus had decreased about 4 logs."}
{"id": "PMID:232663", "title": "Thiourea derivatives as specific inhibitors of picorna viruses.", "content": "30 compounds with antipicorna virus activity were selected from 173 N,N'-disubstituted thiourea derivatives. The spectrum of antiviral activity was determined in vitro using entero, FMD, rhino and EMC viruses. Structure-activity relationships were studied. Several compounds produced marked activity against coxsackie viruses A and B infection of mice and FMD infection in mice and guinea pigs. N-Phenyl-N'-3-hydroxyphenyl-thiourea (PTU-23) inhibited poliovirus production by more than 99% without influencing the FL host cell. EMC virus was readily inhibited by PTU-23 in Kreb-II cells. Virus RNA synthesis was significantly reduced. Under the effect of PTU-23 the amount of 37S ssRNA extracted from EMC virus infected cells was considerably more reduced than that of the 20S ds RNA. PTU-23 did not influence the activity of virus-induced RNA polymerase in a cell-free system.", "contents": "Thiourea derivatives as specific inhibitors of picorna viruses. 30 compounds with antipicorna virus activity were selected from 173 N,N'-disubstituted thiourea derivatives. The spectrum of antiviral activity was determined in vitro using entero, FMD, rhino and EMC viruses. Structure-activity relationships were studied. Several compounds produced marked activity against coxsackie viruses A and B infection of mice and FMD infection in mice and guinea pigs. N-Phenyl-N'-3-hydroxyphenyl-thiourea (PTU-23) inhibited poliovirus production by more than 99% without influencing the FL host cell. EMC virus was readily inhibited by PTU-23 in Kreb-II cells. Virus RNA synthesis was significantly reduced. Under the effect of PTU-23 the amount of 37S ssRNA extracted from EMC virus infected cells was considerably more reduced than that of the 20S ds RNA. PTU-23 did not influence the activity of virus-induced RNA polymerase in a cell-free system."}
{"id": "PMID:232659", "title": "Duck plague: a carrier state in waterfowl.", "content": "Healthy waterfowl were found to be carriers of duck plague (DP) virus. Black ducks (Anas rubripes) and Canada geese (Branta canadensis) surviving a natural outbreak of DP at Coloma, Wisconsin, in 1973 yielded DP virus in cloacal swabs taken four years postinfection. Experimental infection of previously unexposed mallard ducks (Anas platyrhynochos) with the Coloma strain of DP virus CO-WI (73) also produced cloacal virus shedding for up to four years after infection. A second DP virus strain, LA-SD (73) from the Lake Andes, South Dakota, epornitic, was detected from cloacal swabs of pintail ducks (Anas acuta), gadwall ducks (Anas strepera), wood ducks (Aix sponsa), and Canada geese infected experimentally one year before. The frequency of swabs positive for DP virus varied between individuals within each of the tested species. The amount of detectable DP virus shed was about 100 plaqueforming units of virus percloacal swab. Oral erosions were present in all species tested except Canada geese and gadwall ducks. Erosions occurred at the openings of the sublingual salivary gland ducts. DP virus was isolated from erosions. All ducks with lesions proved to shed DP virus, although not necessarily at the time they had the lesion.", "contents": "Duck plague: a carrier state in waterfowl. Healthy waterfowl were found to be carriers of duck plague (DP) virus. Black ducks (Anas rubripes) and Canada geese (Branta canadensis) surviving a natural outbreak of DP at Coloma, Wisconsin, in 1973 yielded DP virus in cloacal swabs taken four years postinfection. Experimental infection of previously unexposed mallard ducks (Anas platyrhynochos) with the Coloma strain of DP virus CO-WI (73) also produced cloacal virus shedding for up to four years after infection. A second DP virus strain, LA-SD (73) from the Lake Andes, South Dakota, epornitic, was detected from cloacal swabs of pintail ducks (Anas acuta), gadwall ducks (Anas strepera), wood ducks (Aix sponsa), and Canada geese infected experimentally one year before. The frequency of swabs positive for DP virus varied between individuals within each of the tested species. The amount of detectable DP virus shed was about 100 plaqueforming units of virus percloacal swab. Oral erosions were present in all species tested except Canada geese and gadwall ducks. Erosions occurred at the openings of the sublingual salivary gland ducts. DP virus was isolated from erosions. All ducks with lesions proved to shed DP virus, although not necessarily at the time they had the lesion."}
{"id": "PMID:232660", "title": "Characterization of Immunosuppression in chickens by infectious bursal disease virus.", "content": "Chickens were infected with infectious bursal disease (IBD) virus in ovo or at different times posthatching to 6 weeks of age. The B- and T-cell responses in the lymphoid tissues and blood were examined sequentially to 8 weeks of age by using indirect immunofluorescence. The proportion of B-cells was consistently lower in infected birds than in controls, especially in chicks infected as embryos or at 1 day old. The proportion of T-cells increased following these early infections but was slightly lower in spleen and blood of birds infected at 1, 4, and-6 weeks of age. Serum IgM levels dropped significantly after infection, regardless of the time of infection. IgG levels decreased following early infection but increased after infection at 1 week old or more. The results strongly suggest that B-cells are the target for IBD virus infection.", "contents": "Characterization of Immunosuppression in chickens by infectious bursal disease virus. Chickens were infected with infectious bursal disease (IBD) virus in ovo or at different times posthatching to 6 weeks of age. The B- and T-cell responses in the lymphoid tissues and blood were examined sequentially to 8 weeks of age by using indirect immunofluorescence. The proportion of B-cells was consistently lower in infected birds than in controls, especially in chicks infected as embryos or at 1 day old. The proportion of T-cells increased following these early infections but was slightly lower in spleen and blood of birds infected at 1, 4, and-6 weeks of age. Serum IgM levels dropped significantly after infection, regardless of the time of infection. IgG levels decreased following early infection but increased after infection at 1 week old or more. The results strongly suggest that B-cells are the target for IBD virus infection."}
{"id": "PMID:232664", "title": "1H NMR study on the interaction of cupric ion with ribonuclease A.", "content": "The reassignment of the 1H NMR C-2 histidine signals of the bovine pancreatic ribonuclease A has required a revision of the 1H NMR data on the role of the different histidines in their interaction with the Cu2+. The results of our measurements carried out at p2H 5.5 and 7.0 reduce the importance of His-12 as main site of interaction. At p2H 5.5 a very strong binding site involves His-119, while a weaker one contains certainly His-105. On the contrary, at p2H 7.0 the histidines 105 and 119 seem to possess binding constants of the same order of magnitude and in addition they provide stronger ligands for the Cu2+ than His-12. The comparison with X-ray data in the crystal shows numerous analogies. Finally, preliminary results on the competitive inhibition effect between the Cu2+ and 2',3'-cytidine monophosphoric acid are discussed.", "contents": "1H NMR study on the interaction of cupric ion with ribonuclease A. The reassignment of the 1H NMR C-2 histidine signals of the bovine pancreatic ribonuclease A has required a revision of the 1H NMR data on the role of the different histidines in their interaction with the Cu2+. The results of our measurements carried out at p2H 5.5 and 7.0 reduce the importance of His-12 as main site of interaction. At p2H 5.5 a very strong binding site involves His-119, while a weaker one contains certainly His-105. On the contrary, at p2H 7.0 the histidines 105 and 119 seem to possess binding constants of the same order of magnitude and in addition they provide stronger ligands for the Cu2+ than His-12. The comparison with X-ray data in the crystal shows numerous analogies. Finally, preliminary results on the competitive inhibition effect between the Cu2+ and 2',3'-cytidine monophosphoric acid are discussed."}
{"id": "PMID:232661", "title": "Interaction of infectious bursal disease and coccidiosis in layer replacement chickens.", "content": "During a floor-pen study on anticoccidial programs for layer-replacement pullets, there was a natural outbreak of infectious bursal disease (IBD). The interaction of coccidiosis and IBD was characterized by: excessive deaths from coccidiosis; and apparent failure of some anticoccidial drug treatments. Immunity to coccidiosis was not blocked by the IBD infection, although immunity was less in some treatments than would be expected with the degree of coccidiosis exposure.", "contents": "Interaction of infectious bursal disease and coccidiosis in layer replacement chickens. During a floor-pen study on anticoccidial programs for layer-replacement pullets, there was a natural outbreak of infectious bursal disease (IBD). The interaction of coccidiosis and IBD was characterized by: excessive deaths from coccidiosis; and apparent failure of some anticoccidial drug treatments. Immunity to coccidiosis was not blocked by the IBD infection, although immunity was less in some treatments than would be expected with the degree of coccidiosis exposure."}
{"id": "PMID:232665", "title": "Isolation of the lymphocytosis promoting factor-haemagglutinin of Bordetella pertussis by affinity chromatography.", "content": "The lymphocytosis promoting factor-haemagglutinin of Bordetella pertussis was isolated from solutions obtained after cell disintegration by a novel affinity chromatographic method using an adsorbent composed of human haptoglobin covalently attached to a Sepharose 4B matrix. The haemagglutinin was bound to the adsorbent at pH 6.5 and eluted by a stepwise change to a pH 10 buffer. A 300--600-fold purification of the haemagglutinin was achieved by this one-step process. The chemical and biological properties of the haemagglutinin isolated by affinity chromatography were found to be similar to those of the protein isolated by other workers from culture supernatants. The affinity chromatographic method was found to be specific for the purification of the lymphocytosis promoting factor-haemagglutinin and no purification of the fimbrial-haemagglutinin of Bordetella pertussis was achieved by the method.", "contents": "Isolation of the lymphocytosis promoting factor-haemagglutinin of Bordetella pertussis by affinity chromatography. The lymphocytosis promoting factor-haemagglutinin of Bordetella pertussis was isolated from solutions obtained after cell disintegration by a novel affinity chromatographic method using an adsorbent composed of human haptoglobin covalently attached to a Sepharose 4B matrix. The haemagglutinin was bound to the adsorbent at pH 6.5 and eluted by a stepwise change to a pH 10 buffer. A 300--600-fold purification of the haemagglutinin was achieved by this one-step process. The chemical and biological properties of the haemagglutinin isolated by affinity chromatography were found to be similar to those of the protein isolated by other workers from culture supernatants. The affinity chromatographic method was found to be specific for the purification of the lymphocytosis promoting factor-haemagglutinin and no purification of the fimbrial-haemagglutinin of Bordetella pertussis was achieved by the method."}
{"id": "PMID:232666", "title": "Cobalt-substituted hemoglobin Z\u00fcrich (alpha 2 beta 263His leads Arg). Oxygen equilibria and EPR spectra.", "content": "Cobalt hemoglobin Z\u00fcrich (alpha 2 beta 263His leads to Arg) has been successfully reconstituted from the apohemoglobin Z\u00fcrich and cobaltous protoporphyrin IX. The oxygen affinity of cobalt hemoglobin Zurich, as well as that of iron hemoglobin Z\u00fcrich, were measured in the absence and presence of organic phosphate and Cl-. The overall oxygen affinity of cobalt hemoglobin Z\u00fcrich was found to be higher and the cooperativity as measured by the n value was smaller than those of cobalt hemoglobin A. Organic phosphate and Cl- affect the oxygen equilibrium properties of cobalt hemoglobin Z\u00fcrich in a manner similar to that of cobalt hemoglobin A, but to a lesser extant than cobalt hemoglobin A. The EPR spectrum of oxy cobalt hemoglobin Z\u00fcrich is less sensitive to the replacement of the buffer system from H2O to 2H2O, indicating that the hydrogen bond between the distal amino acid residue and the bound oxygen is not formed in the abnormal beta subunits. The deoxy EPR spectrum of cobalt hemoglobin Z\u00fcrich is similar to that of deoxy cobalt hemoglobin A, suggesting that the deoxy cobalt hemoglobin Z\u00fcrich is predominantly in the deoxy quaternary structure (T state).", "contents": "Cobalt-substituted hemoglobin Z\u00fcrich (alpha 2 beta 263His leads Arg). Oxygen equilibria and EPR spectra. Cobalt hemoglobin Z\u00fcrich (alpha 2 beta 263His leads to Arg) has been successfully reconstituted from the apohemoglobin Z\u00fcrich and cobaltous protoporphyrin IX. The oxygen affinity of cobalt hemoglobin Zurich, as well as that of iron hemoglobin Z\u00fcrich, were measured in the absence and presence of organic phosphate and Cl-. The overall oxygen affinity of cobalt hemoglobin Z\u00fcrich was found to be higher and the cooperativity as measured by the n value was smaller than those of cobalt hemoglobin A. Organic phosphate and Cl- affect the oxygen equilibrium properties of cobalt hemoglobin Z\u00fcrich in a manner similar to that of cobalt hemoglobin A, but to a lesser extant than cobalt hemoglobin A. The EPR spectrum of oxy cobalt hemoglobin Z\u00fcrich is less sensitive to the replacement of the buffer system from H2O to 2H2O, indicating that the hydrogen bond between the distal amino acid residue and the bound oxygen is not formed in the abnormal beta subunits. The deoxy EPR spectrum of cobalt hemoglobin Z\u00fcrich is similar to that of deoxy cobalt hemoglobin A, suggesting that the deoxy cobalt hemoglobin Z\u00fcrich is predominantly in the deoxy quaternary structure (T state)."}
{"id": "PMID:232667", "title": "[Kinetic parameters of Na,K-ATPase in the gills of crabs adapted to freshened sea water].", "content": "The dependence of Na,K-ATPase activity on concentrations of ATP, Na+, K+, Mg2+ and ouabain in the membrane preparations of crab gills was studied. The first group of crabs was adapted to freshened (25%) and the second one--to normal (100%) sea water. A 40-day adaptation of crabs to the freshened sea water results in an increase of maximal activity of Na,K-ATPase, but does not affect the enzyme affinity for ATP, Na+, K+, Mg2+ and ouabain, as well as its cooperative properties. It is assumed that adaptation of crabs to freshened sea water is accompanied by an accumulation of Na, K-ATPase in the epithelial cell membranes or crab gills without causing any qualitative changes of the enzyme.", "contents": "[Kinetic parameters of Na,K-ATPase in the gills of crabs adapted to freshened sea water]. The dependence of Na,K-ATPase activity on concentrations of ATP, Na+, K+, Mg2+ and ouabain in the membrane preparations of crab gills was studied. The first group of crabs was adapted to freshened (25%) and the second one--to normal (100%) sea water. A 40-day adaptation of crabs to the freshened sea water results in an increase of maximal activity of Na,K-ATPase, but does not affect the enzyme affinity for ATP, Na+, K+, Mg2+ and ouabain, as well as its cooperative properties. It is assumed that adaptation of crabs to freshened sea water is accompanied by an accumulation of Na, K-ATPase in the epithelial cell membranes or crab gills without causing any qualitative changes of the enzyme."}
{"id": "PMID:232668", "title": "[Reconstitution of electrogenic function of pyrophosphatase isolated from Rhodospirillum rubrum membranes].", "content": "The membrane vesicles (proteoliposomes) have been reconstituted from phospholipids and inorganic pyrophosphatase (EC 3.6.1.1) isolated from Rhodospirillum rubrum chromatophores. An addition of inorganic pyrophosphate (PPi) causes a Mg2+-dependent formation of a transmembrane electric potential difference and an uptake of penetrating tetraphenylborate anions by the proteoliposomes. Thus, isolated pyrophosphatase, being incorporated into the phospholipid membrane, functions as a MgPPi-dependent protein generator of the electric current.", "contents": "[Reconstitution of electrogenic function of pyrophosphatase isolated from Rhodospirillum rubrum membranes]. The membrane vesicles (proteoliposomes) have been reconstituted from phospholipids and inorganic pyrophosphatase (EC 3.6.1.1) isolated from Rhodospirillum rubrum chromatophores. An addition of inorganic pyrophosphate (PPi) causes a Mg2+-dependent formation of a transmembrane electric potential difference and an uptake of penetrating tetraphenylborate anions by the proteoliposomes. Thus, isolated pyrophosphatase, being incorporated into the phospholipid membrane, functions as a MgPPi-dependent protein generator of the electric current."}
{"id": "PMID:232669", "title": "Sleep learning during stage 2 and REM sleep.", "content": "Pairs of subjects were presented with a 20-item picture series at bedtime. In the latter part of the night, a tape-recorded series of 10 words, the verbal equivalent of half the original series of pictures, was repeated 10 times during either Stage 2 or REM sleep. Morning recall and recognition for repeated words was found to be facilitated following repetition during Stage 2 sleep, but relatively unaffected following repetition during REM sleep. However, adjusting for recall, the number of additional words elicited through recognition was found to be significantly greater for REM repeated words than for Stage 2 repeated words. It was suggested that retrieval limitations, perhaps as a result of REM state dependency, rather than storage inhibition may be the main locus of the initial recall failure. By comparison, Stage 2 sleep would seem to present both a lower barrier to memory storage and retrieval compatibility with wakefulness.", "contents": "Sleep learning during stage 2 and REM sleep. Pairs of subjects were presented with a 20-item picture series at bedtime. In the latter part of the night, a tape-recorded series of 10 words, the verbal equivalent of half the original series of pictures, was repeated 10 times during either Stage 2 or REM sleep. Morning recall and recognition for repeated words was found to be facilitated following repetition during Stage 2 sleep, but relatively unaffected following repetition during REM sleep. However, adjusting for recall, the number of additional words elicited through recognition was found to be significantly greater for REM repeated words than for Stage 2 repeated words. It was suggested that retrieval limitations, perhaps as a result of REM state dependency, rather than storage inhibition may be the main locus of the initial recall failure. By comparison, Stage 2 sleep would seem to present both a lower barrier to memory storage and retrieval compatibility with wakefulness."}
{"id": "PMID:232670", "title": "Receptors for angiotensin: a critical analysis.", "content": "Angiotensin exerts numerous contractile and secretory effects by activating specific receptors. Recent pharmacological findings obtained with this peptide in various laboratories are analyzed, using the order of potency of agonists and the affinity of competitive antagonists as criteria for the classification of receptors for angiotensin in several systems. The analysis is restricted to experiments in which biological effects have been measured. Desensitization (the third criterion for classification of receptors) is discussed and a new protocol is proposed for its utilization. The analysis reveals that receptors for angiotensin in intestinal and vascular smooth muscles, in the heart, and in the vas deferens are all of the same type, while the receptors mediating the release of catecholamines from the adrenal medulla and those subserving the steroidogenic action on the adrenal cortex remain still unidentified. The recently proposed role of ATI as mediator of renin in the adrenal medulla is not substantiated by pharmacological findings with decapeptide antagonists. Moreover, the utilization of ATI as an agonist to determine the order of potency of angiotensins and the use of SQ 20881 as an inhibitor of the converting enzyme have shown serious limitations and should be reconsidered. The hypothetical role of ATIII as mediator of the renin-angiotensin system in the adrenal cortex, at least in other species than the rat, appears to be supported by the high affinity of heptapeptide antagonists for the adrenocortical receptor. However, these antagonists have generally been compared with [Sar1,Ala8]-ATII, A compound which is definitely inadequate for evaluating the affinities of octapeptides in the adrenal cortex. Therefore most of the data supporting the role of ATIII in this system have to be carefully reconsidered. Analogues of ATII are proposed for using as agonists and as antagonists instead of the natural angiotensins (for determining the order of potency of agonists) and instead of [Sar1,Ala8]-ATII (for measuring the affinities of competitive antagonists).", "contents": "Receptors for angiotensin: a critical analysis. Angiotensin exerts numerous contractile and secretory effects by activating specific receptors. Recent pharmacological findings obtained with this peptide in various laboratories are analyzed, using the order of potency of agonists and the affinity of competitive antagonists as criteria for the classification of receptors for angiotensin in several systems. The analysis is restricted to experiments in which biological effects have been measured. Desensitization (the third criterion for classification of receptors) is discussed and a new protocol is proposed for its utilization. The analysis reveals that receptors for angiotensin in intestinal and vascular smooth muscles, in the heart, and in the vas deferens are all of the same type, while the receptors mediating the release of catecholamines from the adrenal medulla and those subserving the steroidogenic action on the adrenal cortex remain still unidentified. The recently proposed role of ATI as mediator of renin in the adrenal medulla is not substantiated by pharmacological findings with decapeptide antagonists. Moreover, the utilization of ATI as an agonist to determine the order of potency of angiotensins and the use of SQ 20881 as an inhibitor of the converting enzyme have shown serious limitations and should be reconsidered. The hypothetical role of ATIII as mediator of the renin-angiotensin system in the adrenal cortex, at least in other species than the rat, appears to be supported by the high affinity of heptapeptide antagonists for the adrenocortical receptor. However, these antagonists have generally been compared with [Sar1,Ala8]-ATII, A compound which is definitely inadequate for evaluating the affinities of octapeptides in the adrenal cortex. Therefore most of the data supporting the role of ATIII in this system have to be carefully reconsidered. Analogues of ATII are proposed for using as agonists and as antagonists instead of the natural angiotensins (for determining the order of potency of agonists) and instead of [Sar1,Ala8]-ATII (for measuring the affinities of competitive antagonists)."}
{"id": "PMID:232671", "title": "Permeation of sodium through calcium channels of an insect muscle membrane.", "content": "The contribution of Na ions to the electrically excited response was studied in the muscle fibres of mealworm larvae, Tenebrio molitor, using microelectrode techniques. When Ca ions were omitted from the external solution, no action potential could be elicited. However, addition of Na ions to Ca-free medium rendered the fibre excitable again. The amplitude of these action potentials increased with a slope of about 40 mV for a 10-fold elevation of external Na concentrations. Tetrodotoxin had no effect on the initiation of the spike, and Co ions completely suppressed it. Therefore, it seems likely that a Ca-channel, which is utilized by both Na and Ca ions, is the sole factor responsible for the action potential in the mealworm larval muscle fibre membrane.", "contents": "Permeation of sodium through calcium channels of an insect muscle membrane. The contribution of Na ions to the electrically excited response was studied in the muscle fibres of mealworm larvae, Tenebrio molitor, using microelectrode techniques. When Ca ions were omitted from the external solution, no action potential could be elicited. However, addition of Na ions to Ca-free medium rendered the fibre excitable again. The amplitude of these action potentials increased with a slope of about 40 mV for a 10-fold elevation of external Na concentrations. Tetrodotoxin had no effect on the initiation of the spike, and Co ions completely suppressed it. Therefore, it seems likely that a Ca-channel, which is utilized by both Na and Ca ions, is the sole factor responsible for the action potential in the mealworm larval muscle fibre membrane."}
{"id": "PMID:232674", "title": "Purification of soluble hepatocellular carcinoma extracts.", "content": "When soluble hepatocellular carcinoma (HCC) extract prepared by 3 M KCl solution was passed through a column of Sephadex G-200, four fractions (designated as I, II, III, IV) could be obtained from the elution profile. By leukocyte migration inhibition assay, the active component of soluble HCC extract which represented tumor-associated antigen was shown to be contained in fractions I and II.", "contents": "Purification of soluble hepatocellular carcinoma extracts. When soluble hepatocellular carcinoma (HCC) extract prepared by 3 M KCl solution was passed through a column of Sephadex G-200, four fractions (designated as I, II, III, IV) could be obtained from the elution profile. By leukocyte migration inhibition assay, the active component of soluble HCC extract which represented tumor-associated antigen was shown to be contained in fractions I and II."}
{"id": "PMID:232675", "title": "Sulfatide synthesis by neural cell lines.", "content": "Several neural cell lines were examined for their ability to synthesize sulfatide and 2',3'-cyclic nucleotide phosphohydrolase, biochemical components characteristic of myelin. The mouse glioma G26 and the rat schwannoma TRM6B actively produced sulfatide, while the rat glioma C6 was inactive, supporting the probable oligodendroglial origin of the G26. In contrast, the C6 cell line had a high level of 2'-3'-cyclic nucleotide phosphohydrolase activity, while TRM6B showed 30% and the G26 75% lower activities. Thus, these two activities appear to be independently regulated.", "contents": "Sulfatide synthesis by neural cell lines. Several neural cell lines were examined for their ability to synthesize sulfatide and 2',3'-cyclic nucleotide phosphohydrolase, biochemical components characteristic of myelin. The mouse glioma G26 and the rat schwannoma TRM6B actively produced sulfatide, while the rat glioma C6 was inactive, supporting the probable oligodendroglial origin of the G26. In contrast, the C6 cell line had a high level of 2'-3'-cyclic nucleotide phosphohydrolase activity, while TRM6B showed 30% and the G26 75% lower activities. Thus, these two activities appear to be independently regulated."}
{"id": "PMID:232677", "title": "Effect of prostaglandins on milk ejection.", "content": "Prostaglandins (PGs) of type F2 alpha, E1, and E2 have been reported both, to inhibit or to facilitate posterior pituitary oxytocin release in lactating animals and women, and to suppress or to stimulate the mammary myoepithelium. Prostaglandin-induced milk ejection in women and cows has been attributed to central oxytocin release, but no oxytocin blood levels were determined. Moreover, for lactating cows, sows, rabbits, guinea pigs, and rats a direct PG effect on the mammary myoepithelium resulting in milk ejection has been suggested. On the other hand, PGs were found to antagonize the milk-ejection response to oxytocin in rabbits and rats. The mechanisms involved in PG synergism or antagonism of oxytocin-induced milk ejection are not understood. Studies in lactating rats showed that blood pressure active PG doses of F2 alpha, E1, and E2 largely inhibited the intramammary pressure response to oxytocin. Whereas the oxytocin-antagonistic action of PGF2 alpha was not affected by adrenergic blockers (phenoxybenzamine, propranolol), the anti-oxytocin effects of PGE1 and E2 were eliminated after alpha-receptor blockade while the activity of oxytocin increased. Under beta-receptor or alpha- plus beta-receptor blockade, the oxytocin-inhibitory effects of PGE1 and E2 were almost abolished. Mechanisms of PG-induced inhibition of the oxytocin response may involve mammary vascular changes and/or alterations in myoepithelial activity of cyclic adenosine-3,5-monophosphate (c-AMP), cyclic guanosine-3,5-monophosphate (c-GMP), and phosphodiesterase (PDE). It seems unlikely that PGs bring about significant posterior pituitary oxytocin release in rats.", "contents": "Effect of prostaglandins on milk ejection. Prostaglandins (PGs) of type F2 alpha, E1, and E2 have been reported both, to inhibit or to facilitate posterior pituitary oxytocin release in lactating animals and women, and to suppress or to stimulate the mammary myoepithelium. Prostaglandin-induced milk ejection in women and cows has been attributed to central oxytocin release, but no oxytocin blood levels were determined. Moreover, for lactating cows, sows, rabbits, guinea pigs, and rats a direct PG effect on the mammary myoepithelium resulting in milk ejection has been suggested. On the other hand, PGs were found to antagonize the milk-ejection response to oxytocin in rabbits and rats. The mechanisms involved in PG synergism or antagonism of oxytocin-induced milk ejection are not understood. Studies in lactating rats showed that blood pressure active PG doses of F2 alpha, E1, and E2 largely inhibited the intramammary pressure response to oxytocin. Whereas the oxytocin-antagonistic action of PGF2 alpha was not affected by adrenergic blockers (phenoxybenzamine, propranolol), the anti-oxytocin effects of PGE1 and E2 were eliminated after alpha-receptor blockade while the activity of oxytocin increased. Under beta-receptor or alpha- plus beta-receptor blockade, the oxytocin-inhibitory effects of PGE1 and E2 were almost abolished. Mechanisms of PG-induced inhibition of the oxytocin response may involve mammary vascular changes and/or alterations in myoepithelial activity of cyclic adenosine-3,5-monophosphate (c-AMP), cyclic guanosine-3,5-monophosphate (c-GMP), and phosphodiesterase (PDE). It seems unlikely that PGs bring about significant posterior pituitary oxytocin release in rats."}
{"id": "PMID:232678", "title": "[Diabetic polyneuropathy. 4. Synopsis of electroneurographic findings in diabetics].", "content": "Sensory conduction velocity of the median nerve, motor conduction velocity of both median and tibial nerves, and corresponding distal laterncies are sufficient parameters to establish the diagnosis of polyneuropathy almost with certainty. Considering these six parameters yielded in detection of peripheral nerve dysfunction in 22% of diabetic patients who were free from clinical signs of polyneuropathy. Electroneurographical findings in 340 out of 677 patients with diabetes mellitus were interpreted as evidence of segmental demyelination. Within this group there was the majority of patients with clinical signs of polyneuropathy and with subclinical signs of peripheral nerve dysfunction. There existed a positive correlation between signs of nerve dysfunction with angiopathy, age and duration of the disease. A second group consisting of 243 diabetics with signs of incipient segmental demyelination with or without signs of axonaal degeneration mainly included juvenile patients with a short duration of the disease and with a low frequency of angiopathy.", "contents": "[Diabetic polyneuropathy. 4. Synopsis of electroneurographic findings in diabetics]. Sensory conduction velocity of the median nerve, motor conduction velocity of both median and tibial nerves, and corresponding distal laterncies are sufficient parameters to establish the diagnosis of polyneuropathy almost with certainty. Considering these six parameters yielded in detection of peripheral nerve dysfunction in 22% of diabetic patients who were free from clinical signs of polyneuropathy. Electroneurographical findings in 340 out of 677 patients with diabetes mellitus were interpreted as evidence of segmental demyelination. Within this group there was the majority of patients with clinical signs of polyneuropathy and with subclinical signs of peripheral nerve dysfunction. There existed a positive correlation between signs of nerve dysfunction with angiopathy, age and duration of the disease. A second group consisting of 243 diabetics with signs of incipient segmental demyelination with or without signs of axonaal degeneration mainly included juvenile patients with a short duration of the disease and with a low frequency of angiopathy."}
{"id": "PMID:232681", "title": "Painful ophthalmoplegia: the Tolosa-Hunt syndrome.", "content": "Painful ophthalmoplegia is characterized by unilateral involvement of the IIIrd, IVth and VIth cranial nerves, as well as supra- and retro-orbital pain, i.e. participation of the Vth cranial nerve. The pain is relieved within 48-72 h with steroid therapy. The paresis of the eye muscles in various combinations usually subsides gradually from within a few weeks to several months. The etiology is unknown. The few pathological examinations reported in the literature showed an unspecific inflammatory granulation tissue around the intracavernous portion of the carotid artery and on the dura mater in the vicinity of the cavernous sinus. Carotid arteriography may show stationary waves of this artery and narrowing of its intracavernous portion. With orbital phlebography the occlusion of the supraorbital vein and obstruction of the cavernous sinus are sometimes demonstrable. The syndrome is well defined and its etiology still unknown.", "contents": "Painful ophthalmoplegia: the Tolosa-Hunt syndrome. Painful ophthalmoplegia is characterized by unilateral involvement of the IIIrd, IVth and VIth cranial nerves, as well as supra- and retro-orbital pain, i.e. participation of the Vth cranial nerve. The pain is relieved within 48-72 h with steroid therapy. The paresis of the eye muscles in various combinations usually subsides gradually from within a few weeks to several months. The etiology is unknown. The few pathological examinations reported in the literature showed an unspecific inflammatory granulation tissue around the intracavernous portion of the carotid artery and on the dura mater in the vicinity of the cavernous sinus. Carotid arteriography may show stationary waves of this artery and narrowing of its intracavernous portion. With orbital phlebography the occlusion of the supraorbital vein and obstruction of the cavernous sinus are sometimes demonstrable. The syndrome is well defined and its etiology still unknown."}
{"id": "PMID:232682", "title": "Electroneurographic investigations of misonidazole polyneuropathy.", "content": "13 patients with malignant tumors were treated by the radiosensitizer misonidazole (Ro 07-0582), total dosage 20-29 g. The electrophysiological investigations showed (1) an early increase of distal latency, the motor nerve conduction velocity (NCV) of the peroneal nerve and the NCV of the sural nerve remaining normal or only signlty reduced, and in a few cases a marked reduction of the compound action potential or of the nerve action potential (NAP), indicating a primary axonal neuropathy; (2) greater changes in the parameters of sensory nerves (n. suralis) than of motor nerves; (3) the distal latency is a good indicator of subclinical neuropathies; (4) the electrophysiological parameters showed a normalization 6 months after the end of therapy. The mechanisms possibly responsible for the misonidazole neuropathy are discussed.", "contents": "Electroneurographic investigations of misonidazole polyneuropathy. 13 patients with malignant tumors were treated by the radiosensitizer misonidazole (Ro 07-0582), total dosage 20-29 g. The electrophysiological investigations showed (1) an early increase of distal latency, the motor nerve conduction velocity (NCV) of the peroneal nerve and the NCV of the sural nerve remaining normal or only signlty reduced, and in a few cases a marked reduction of the compound action potential or of the nerve action potential (NAP), indicating a primary axonal neuropathy; (2) greater changes in the parameters of sensory nerves (n. suralis) than of motor nerves; (3) the distal latency is a good indicator of subclinical neuropathies; (4) the electrophysiological parameters showed a normalization 6 months after the end of therapy. The mechanisms possibly responsible for the misonidazole neuropathy are discussed."}
{"id": "PMID:232689", "title": "Alterations in lung macrophage antimicrobial activity associated with viral pneumonia.", "content": "Secondary bacterial infections are a common sequelae of viral pneumonias. To study 2 functions of the phagocytic defenses of the lung, macrophages were obtained by lung lavage from parainfluenza 1 virus-infected and noninfected mice. The phagocytic capacities (binding, ingestion, and killing) of these cells were assessed in vitro against viable Candida krusei. Viral pneumonia resulted in a progressive suppression (through day 7 of the infection) of the ability of macrophages to bind candida to their surfaces by nonimmunological or complement receptors; ingestion and intracellular killing of candida were also decreased. After day 7, all these functions returned and, in fact, cells with enhanced activities were present on day 17. After introduction of virus into the lungs, the lung macrophage population increased significantly between days 3 and 7 of infection. This resulted in an increase in the phagocytic potential of the lung, despite the virus-associated suppression of the phagocytic activity in a portion of the macrophages. However, the ability of the macrophages to kill ingested microorganisms was also reduced, resulting in an overall deficiency in the lung macrophage defenses. It was concluded that viral pneumonia was associated with at least two suppressive effects on the lung macrophage-decreased receptor activity and microbicidal activity-resulting in a deficiency in the lung phagocytic defenses represented by these cells. These effects were maximal 1 week after infection and could account for the increased susceptibility of these lungs to secondary bacterial pneumonias. In contrast, during the period of convalescence, the lung macrophage antimicrobial activities were increased and reflected in enhanced resistance of the lungs to infections.", "contents": "Alterations in lung macrophage antimicrobial activity associated with viral pneumonia. Secondary bacterial infections are a common sequelae of viral pneumonias. To study 2 functions of the phagocytic defenses of the lung, macrophages were obtained by lung lavage from parainfluenza 1 virus-infected and noninfected mice. The phagocytic capacities (binding, ingestion, and killing) of these cells were assessed in vitro against viable Candida krusei. Viral pneumonia resulted in a progressive suppression (through day 7 of the infection) of the ability of macrophages to bind candida to their surfaces by nonimmunological or complement receptors; ingestion and intracellular killing of candida were also decreased. After day 7, all these functions returned and, in fact, cells with enhanced activities were present on day 17. After introduction of virus into the lungs, the lung macrophage population increased significantly between days 3 and 7 of infection. This resulted in an increase in the phagocytic potential of the lung, despite the virus-associated suppression of the phagocytic activity in a portion of the macrophages. However, the ability of the macrophages to kill ingested microorganisms was also reduced, resulting in an overall deficiency in the lung macrophage defenses. It was concluded that viral pneumonia was associated with at least two suppressive effects on the lung macrophage-decreased receptor activity and microbicidal activity-resulting in a deficiency in the lung phagocytic defenses represented by these cells. These effects were maximal 1 week after infection and could account for the increased susceptibility of these lungs to secondary bacterial pneumonias. In contrast, during the period of convalescence, the lung macrophage antimicrobial activities were increased and reflected in enhanced resistance of the lungs to infections."}
{"id": "PMID:232690", "title": "Pathogenesis of Marek's disease; effect of immunization with inactivated viral and tumor-associated antigens.", "content": "Inactivated Marek's disease virus-infected chicken kidney cells and inactivated MSB-1 lymphoblastoid Marek's disease tumor cells were used to immunize chickens as virus- and tumor-associated antigens, respectively. Immune and nonimmune birds were then challenged by exposure to live virulent Marek's disease virus. Both vaccines protected significant numbers of chickens (P less than 0.05) against subsequent tumor development, although viral antigen appeared superior to tumor antigen. After challenge, the early appearance of viral antigen, infected lymphocytes, and degenerative changes in lymphoid organs was inhibited only by the viral antigen vaccine, whereas the early appearance of cells bearing tumor antigen was prevented by both vaccines. These results support the hypothesis that effective immunity in Marek's disease could be directed against either virus replication and spread or events associated with transformation and proliferation of lymphoid cells.", "contents": "Pathogenesis of Marek's disease; effect of immunization with inactivated viral and tumor-associated antigens. Inactivated Marek's disease virus-infected chicken kidney cells and inactivated MSB-1 lymphoblastoid Marek's disease tumor cells were used to immunize chickens as virus- and tumor-associated antigens, respectively. Immune and nonimmune birds were then challenged by exposure to live virulent Marek's disease virus. Both vaccines protected significant numbers of chickens (P less than 0.05) against subsequent tumor development, although viral antigen appeared superior to tumor antigen. After challenge, the early appearance of viral antigen, infected lymphocytes, and degenerative changes in lymphoid organs was inhibited only by the viral antigen vaccine, whereas the early appearance of cells bearing tumor antigen was prevented by both vaccines. These results support the hypothesis that effective immunity in Marek's disease could be directed against either virus replication and spread or events associated with transformation and proliferation of lymphoid cells."}
{"id": "PMID:232691", "title": "Neuraminidase-dependent hamagglutination of human erythrocytes by human strains of Actinomyces viscosus and Actinomyces naeslundii.", "content": "Human A, B, and O erythrocytes (RBC) were agglutinated by many human strains of Actinomyces viscosus and A. naeslundii. At 37 degrees C, these bacterium-mediated hemagglutination reactions required the action of bacterial neuraminidase upon the RBC; however, at 4 degrees C, the requirement for neuraminidase was not as striking. Bacterial cell suspensions which caused hemagglutination at 37 degrees C contained both soluble extracellular and cell-associated neuraminidase activities as shown by enzyme assays using a soluble substrate (i.e., alpha 1-acid glycoprotein). Bacterium-mediated hemagglutination occurred only in the presence of soluble neuraminidase activity, and the rate of hemagglutination could be inhibited by 2-deoxy-2,3-dehydro-N-acetylneuraminic acid, a competitive inhibitor of purified soluble neuraminidase from A. viscosus T14V. Suspensions of bacteria which contained only cell-associated neuraminidase activity were unable to initiate hemagglutination, but they caused immediate hemagglutination when mixed with neuraminidase-treated RBC. All hemagglutination reactions were reversible in the presence of 0.02 M lactose and were abolished by heating (85 degrees C for 30 min) the actinomycete cells but not the RBC. The proposed mechanism of hemagglutination involves two sequential steps: (i) the action of neuraminidase to unmask galactose-containing receptors on the RBC and (ii) the multivalent binding of these receptors by many low-affinity lection sites on the bacterial surface.", "contents": "Neuraminidase-dependent hamagglutination of human erythrocytes by human strains of Actinomyces viscosus and Actinomyces naeslundii. Human A, B, and O erythrocytes (RBC) were agglutinated by many human strains of Actinomyces viscosus and A. naeslundii. At 37 degrees C, these bacterium-mediated hemagglutination reactions required the action of bacterial neuraminidase upon the RBC; however, at 4 degrees C, the requirement for neuraminidase was not as striking. Bacterial cell suspensions which caused hemagglutination at 37 degrees C contained both soluble extracellular and cell-associated neuraminidase activities as shown by enzyme assays using a soluble substrate (i.e., alpha 1-acid glycoprotein). Bacterium-mediated hemagglutination occurred only in the presence of soluble neuraminidase activity, and the rate of hemagglutination could be inhibited by 2-deoxy-2,3-dehydro-N-acetylneuraminic acid, a competitive inhibitor of purified soluble neuraminidase from A. viscosus T14V. Suspensions of bacteria which contained only cell-associated neuraminidase activity were unable to initiate hemagglutination, but they caused immediate hemagglutination when mixed with neuraminidase-treated RBC. All hemagglutination reactions were reversible in the presence of 0.02 M lactose and were abolished by heating (85 degrees C for 30 min) the actinomycete cells but not the RBC. The proposed mechanism of hemagglutination involves two sequential steps: (i) the action of neuraminidase to unmask galactose-containing receptors on the RBC and (ii) the multivalent binding of these receptors by many low-affinity lection sites on the bacterial surface."}
{"id": "PMID:232692", "title": "Resistance of C58 mice to primary systemic herpes simplex virus infection: macrophage dependence and T-cell independence.", "content": "The relative contribution of thymus-derived lymphocytes (T-cells) and of macrophages to resistance to primary infection with herpes simplex virus type 1 (HSV-1) was studied in C58 mice. Resistance was dependent on macrophage competence, but was relatively independent of T-lymphocyte competence. Although aging mice became progressively more deficient in functional T-cells, as demonstrated by a decreasing resistance to transplanted line Ib leukemia and by declining responses to T-cell nitogens (concanavalin A and phytohemagglutinin), their resistance to HSV-1 increased with increasing age. Moreover, in mice that were made selectively deficient in T-cells by the combination of adult thymectomy and treatment with anti-thymocyte serum, resistance to HSV-1 did not correlate spleen and mesenteric lymph nodes. However, selective reduction of macrophages by intraperitoneal injection of silica resulted in enhanced susceptibility to HSV-1. Furthermore, in vitro suppression of HSV-1 plaque formation in mouse embryo fibroblast cells was obtained by cocultivation of infected fibroblast monolayers with peritoneal macrophages, but not with splenic lymphocytes, from adult mice. Macrophages from weanling mice failed to suppress the development of plaques, indicating that the increase in resistance to HSV-1 with age is a result of increased macrophage competence.", "contents": "Resistance of C58 mice to primary systemic herpes simplex virus infection: macrophage dependence and T-cell independence. The relative contribution of thymus-derived lymphocytes (T-cells) and of macrophages to resistance to primary infection with herpes simplex virus type 1 (HSV-1) was studied in C58 mice. Resistance was dependent on macrophage competence, but was relatively independent of T-lymphocyte competence. Although aging mice became progressively more deficient in functional T-cells, as demonstrated by a decreasing resistance to transplanted line Ib leukemia and by declining responses to T-cell nitogens (concanavalin A and phytohemagglutinin), their resistance to HSV-1 increased with increasing age. Moreover, in mice that were made selectively deficient in T-cells by the combination of adult thymectomy and treatment with anti-thymocyte serum, resistance to HSV-1 did not correlate spleen and mesenteric lymph nodes. However, selective reduction of macrophages by intraperitoneal injection of silica resulted in enhanced susceptibility to HSV-1. Furthermore, in vitro suppression of HSV-1 plaque formation in mouse embryo fibroblast cells was obtained by cocultivation of infected fibroblast monolayers with peritoneal macrophages, but not with splenic lymphocytes, from adult mice. Macrophages from weanling mice failed to suppress the development of plaques, indicating that the increase in resistance to HSV-1 with age is a result of increased macrophage competence."}
{"id": "PMID:232693", "title": "Infection of cultured human type II pneumonocytes with certain respiratory viruses.", "content": "Human type II alveolar pneumonocytes were grown either as monolayers derived from a clone or as organotypic cultures of fetal lung. The type II cells in these cultures retained in their cytoplasm multilamellar bodies which were morphologically identical to similar organelles present in type II cells of intact human fetal and adult lung. A number of respiratory viruses infected the cells and produced a cytopathic effect in the cultures. Viral components were also detected in some of the infected cells. Adenovirus type 3, human coronavirus 229E, and rhinovirus types 2 and 9 produced new infectious virus, but influenza A and parainfluenza 3 virus apparently did not.", "contents": "Infection of cultured human type II pneumonocytes with certain respiratory viruses. Human type II alveolar pneumonocytes were grown either as monolayers derived from a clone or as organotypic cultures of fetal lung. The type II cells in these cultures retained in their cytoplasm multilamellar bodies which were morphologically identical to similar organelles present in type II cells of intact human fetal and adult lung. A number of respiratory viruses infected the cells and produced a cytopathic effect in the cultures. Viral components were also detected in some of the infected cells. Adenovirus type 3, human coronavirus 229E, and rhinovirus types 2 and 9 produced new infectious virus, but influenza A and parainfluenza 3 virus apparently did not."}
{"id": "PMID:232694", "title": "Comparison of methods for immunocytochemical detection of rotavirus infections.", "content": "Rotavirus infections in intestinal tissues of animals or in tissue culture cells were detected by the immunocytochemical unlabeled soluble enzyme peroxidase antiperoxidase method. Comparison of the immunofluorescence and peroxidase antiperoxidase immunological staining techniques revealed that the two methods are equally sensitive for detection of rotavirus-infected cells. The peroxidase antiperoxidase technique offers the advantages of negligible nonspecific staining reactions, the use of a standard light microscope, the production of permanent slides, and the conservation of immunological reagents. The ability to detect antigens in paraffin-embedded tissues enhances the usefulness of the peroxidase antiperoxidase test for both prospective and retrospective studies.", "contents": "Comparison of methods for immunocytochemical detection of rotavirus infections. Rotavirus infections in intestinal tissues of animals or in tissue culture cells were detected by the immunocytochemical unlabeled soluble enzyme peroxidase antiperoxidase method. Comparison of the immunofluorescence and peroxidase antiperoxidase immunological staining techniques revealed that the two methods are equally sensitive for detection of rotavirus-infected cells. The peroxidase antiperoxidase technique offers the advantages of negligible nonspecific staining reactions, the use of a standard light microscope, the production of permanent slides, and the conservation of immunological reagents. The ability to detect antigens in paraffin-embedded tissues enhances the usefulness of the peroxidase antiperoxidase test for both prospective and retrospective studies."}
{"id": "PMID:232695", "title": "Appearance of immunoglobulin G Fc receptor in cultured human cells infected with varicella-zoster virus.", "content": "After infection with varicella-zoster virus, HeLa and human embryo lung cells developed a receptor for the Fc portion of human and rabbit immunoglobulin G. The receptor was detected by both hemadsorption and immunofluorescence, using antibody-coated erythrocytes and heat-aggregated immunoglobulin G. However, sheep erythrocytes sensitized with F(ab')2 of anti-sheep erythrocyte antibody did not adsorb to the receptor. When cell-free varicella-zoster virus was inoculated into the HeLa cell monolayer, the Fc receptor appeared at first 6 h after infection; varicella-zoster virus antigen in the cytoplasm and detectable cytopathic effects appeared later.", "contents": "Appearance of immunoglobulin G Fc receptor in cultured human cells infected with varicella-zoster virus. After infection with varicella-zoster virus, HeLa and human embryo lung cells developed a receptor for the Fc portion of human and rabbit immunoglobulin G. The receptor was detected by both hemadsorption and immunofluorescence, using antibody-coated erythrocytes and heat-aggregated immunoglobulin G. However, sheep erythrocytes sensitized with F(ab')2 of anti-sheep erythrocyte antibody did not adsorb to the receptor. When cell-free varicella-zoster virus was inoculated into the HeLa cell monolayer, the Fc receptor appeared at first 6 h after infection; varicella-zoster virus antigen in the cytoplasm and detectable cytopathic effects appeared later."}
{"id": "PMID:232696", "title": "Studies on antibody to hepatitis A virus in children and adults in London.", "content": "366 specimens of serum from children and adults without liver disease were screened for antibody to hepatitis A virus (anti-HAV) by means of radioimmunoassay. 56% were born in London, 26% came to London from various parts of the United Kingdom and the remainder (18%) from various parts of the world. The prevalence of antibody was related to increasing age, ranging from 7% in children under ten years of age to 77% in adults aged 50 years or more. The prevalence of anti-HAV was significantly higher in females, in the lower socio-economic class and in those not indigenous to London. In comparison to other urban populations such as those of the United States and Western Europe, the prevalence of anti-HAV was similar in terms of the overall prevalence and age distribution. By contrast, these findings were entirely different from the countries of Eastern Europe and the Middle East where the overall prevalence was higher but the anti-HAV was equal in all ages. Thus, the findings presented indicate that hepatitis A virus infection is common in London and also shows a clear relationship to advancing age, lower socioeconomic class and the country of origin.", "contents": "Studies on antibody to hepatitis A virus in children and adults in London. 366 specimens of serum from children and adults without liver disease were screened for antibody to hepatitis A virus (anti-HAV) by means of radioimmunoassay. 56% were born in London, 26% came to London from various parts of the United Kingdom and the remainder (18%) from various parts of the world. The prevalence of antibody was related to increasing age, ranging from 7% in children under ten years of age to 77% in adults aged 50 years or more. The prevalence of anti-HAV was significantly higher in females, in the lower socio-economic class and in those not indigenous to London. In comparison to other urban populations such as those of the United States and Western Europe, the prevalence of anti-HAV was similar in terms of the overall prevalence and age distribution. By contrast, these findings were entirely different from the countries of Eastern Europe and the Middle East where the overall prevalence was higher but the anti-HAV was equal in all ages. Thus, the findings presented indicate that hepatitis A virus infection is common in London and also shows a clear relationship to advancing age, lower socioeconomic class and the country of origin."}
{"id": "PMID:232697", "title": "A comparative trial of pivmecillinam and ampicillin in bacteriuria of pregnancy.", "content": "A comparative trial of pivmecillinam and ampicillin was performed on 100 women with bacteriuria of pregnancy. They received either 400 mg pivmecillinam four times daily or 500 mg ampicillin four times daily for seven days. Cure rates at two weeks were 88% in the pivmecillinam group and 85% in the ampicillin group. At six weeks the respective rates were 76% and 64%. Failure of therapy was not associated with the appearance of bacterial resistance in either treatment group. Side-effects, particularly vomiting and premature cessation of therapy, were significantly more frequent in the pivmecillinam group. No significant effects on liver function were found. In subsequent patients treated in a non-comparative manner with 200 mg pivmecillinam three times daily, the incidence of side effects was markedly reduced with no loss of efficacy.", "contents": "A comparative trial of pivmecillinam and ampicillin in bacteriuria of pregnancy. A comparative trial of pivmecillinam and ampicillin was performed on 100 women with bacteriuria of pregnancy. They received either 400 mg pivmecillinam four times daily or 500 mg ampicillin four times daily for seven days. Cure rates at two weeks were 88% in the pivmecillinam group and 85% in the ampicillin group. At six weeks the respective rates were 76% and 64%. Failure of therapy was not associated with the appearance of bacterial resistance in either treatment group. Side-effects, particularly vomiting and premature cessation of therapy, were significantly more frequent in the pivmecillinam group. No significant effects on liver function were found. In subsequent patients treated in a non-comparative manner with 200 mg pivmecillinam three times daily, the incidence of side effects was markedly reduced with no loss of efficacy."}
{"id": "PMID:232698", "title": "Propagation of human hepatitis A virus in a hepatoma cell line.", "content": "Hepatitis A virus (HAV) was isolated directly from human feces and propagated serially in an HBsAg producing human hepatoma cell line. No cytopathic effect was observed in the tissue culture and no detectable amounts of HAV were present in the tissue culture supernatant fluid. However, increasing amounts of hepatitis A antigen (HAAg) were detected by radioimmunoassay in the cell extracts obtained by freezing and thawing of cells. Specificity of the HAAg determination was shown by neutralization with convalescent sera of marmosets experimentally infected with the MS-1 strain of hepatitis A and by the absence of this neutralization with preinoculation sera. HAAg was first detected after four weeks in the cell extract of infected cultures after inoculation of 10(2)--10(4) tissue culture infectious doses of HAV from second passage.", "contents": "Propagation of human hepatitis A virus in a hepatoma cell line. Hepatitis A virus (HAV) was isolated directly from human feces and propagated serially in an HBsAg producing human hepatoma cell line. No cytopathic effect was observed in the tissue culture and no detectable amounts of HAV were present in the tissue culture supernatant fluid. However, increasing amounts of hepatitis A antigen (HAAg) were detected by radioimmunoassay in the cell extracts obtained by freezing and thawing of cells. Specificity of the HAAg determination was shown by neutralization with convalescent sera of marmosets experimentally infected with the MS-1 strain of hepatitis A and by the absence of this neutralization with preinoculation sera. HAAg was first detected after four weeks in the cell extract of infected cultures after inoculation of 10(2)--10(4) tissue culture infectious doses of HAV from second passage."}
{"id": "PMID:232699", "title": "A spin-label study of the effect of gamma radiation on erythrocyte membrane. Influence of lipid peroxidation on membrane structure.", "content": "Gamma-irradiation of bovine erythrocyte membranes (0.1-4 Mrad) resulted in a decrease in the degree of order of membrane lipids, as measured by spin-labelled fatty acid esters, at the depth of C12 but not at the depth of C5. Dose dependence of this phenomenon corresponded to dose dependence of malondialdehyde formation in the membranes. On this basis a mechanism for the effect of lipid peroxidation on the membrance structure is proposed. Membrane proteins underwent radiation-induced conformational transitions revealed by maleimide spin label which could be also connected with lipid peroxidation.", "contents": "A spin-label study of the effect of gamma radiation on erythrocyte membrane. Influence of lipid peroxidation on membrane structure. Gamma-irradiation of bovine erythrocyte membranes (0.1-4 Mrad) resulted in a decrease in the degree of order of membrane lipids, as measured by spin-labelled fatty acid esters, at the depth of C12 but not at the depth of C5. Dose dependence of this phenomenon corresponded to dose dependence of malondialdehyde formation in the membranes. On this basis a mechanism for the effect of lipid peroxidation on the membrance structure is proposed. Membrane proteins underwent radiation-induced conformational transitions revealed by maleimide spin label which could be also connected with lipid peroxidation."}
{"id": "PMID:232703", "title": "Stability-indicating assay for mecillinam using high-pressure liquid chromatography.", "content": "A high-pressure liquid chromatographic method has been developed for use as a stability-indicating assay for mecillinam. Seven related compounds and at least one unknown degradation product are well separated and easily determined. The accuracy of the method is in good agreement with the published UV assay and the precision of a series of seven replicate determinations is +/- 1.0% R.S.D.", "contents": "Stability-indicating assay for mecillinam using high-pressure liquid chromatography. A high-pressure liquid chromatographic method has been developed for use as a stability-indicating assay for mecillinam. Seven related compounds and at least one unknown degradation product are well separated and easily determined. The accuracy of the method is in good agreement with the published UV assay and the precision of a series of seven replicate determinations is +/- 1.0% R.S.D."}
{"id": "PMID:232706", "title": "Urine analysis of platinum species derived from cis-dichlorodiammineplatinum(II) by high-performance liquid chromatography following derivatization with sodium diethyldithiocarbamate.", "content": "A clinically useful method is described for the quantitative analysis of platinum species derived from cis-dichlorodiammineplatinum(II) in urine. The drug and its biodegradation products are derivatized directly in urine by reaction with sodium diethyldithiocarbamate (DDTC) to form a common product, a 2:1 DDTC-platinum adduct. This complex is stable and can be quantitatively extracted into 0.1 volumes of chloroform. An aliquot of the chloroform layer is then subjected to high-performance liquid chromatography on a muBondapak CN column and the eluent monitored spectrophotometrically at 254 nm. At this wavelength the DDTC-platinum adduct has a molar absorptivity of 43,000, and platinum levels of 25 ng/ml or urine can be detected with a precision of +/- 2.5% and an accuracy of +/- 4%.", "contents": "Urine analysis of platinum species derived from cis-dichlorodiammineplatinum(II) by high-performance liquid chromatography following derivatization with sodium diethyldithiocarbamate. A clinically useful method is described for the quantitative analysis of platinum species derived from cis-dichlorodiammineplatinum(II) in urine. The drug and its biodegradation products are derivatized directly in urine by reaction with sodium diethyldithiocarbamate (DDTC) to form a common product, a 2:1 DDTC-platinum adduct. This complex is stable and can be quantitatively extracted into 0.1 volumes of chloroform. An aliquot of the chloroform layer is then subjected to high-performance liquid chromatography on a muBondapak CN column and the eluent monitored spectrophotometrically at 254 nm. At this wavelength the DDTC-platinum adduct has a molar absorptivity of 43,000, and platinum levels of 25 ng/ml or urine can be detected with a precision of +/- 2.5% and an accuracy of +/- 4%."}
{"id": "PMID:232708", "title": "Combined high-performance liquid chromatography and radioimmunoassay method for the analysis of delta 9-tetrahydrocannabinol metabolites in human urine.", "content": "A high-performance liquid chromatography-radioimmunoassay method for the measurement of cannabinoids in urine is described. The method involves chromatographing a hydrolysed urine sample with high-performance liquid chromatography and quantifying the eluting cross-reacting cannabinoids with radioimmunoassay. It has been applied to the analysis of cannabinoids in human urine obtained from subjects who had smoked delta 9-tetrahydrocannabinol and the identities of some of the cross-reacting cannabinoids have been established by gas chromatography-mass spectrometry. The method is suitable for use as a routine procedure for cannabinoid analysis in urine.", "contents": "Combined high-performance liquid chromatography and radioimmunoassay method for the analysis of delta 9-tetrahydrocannabinol metabolites in human urine. A high-performance liquid chromatography-radioimmunoassay method for the measurement of cannabinoids in urine is described. The method involves chromatographing a hydrolysed urine sample with high-performance liquid chromatography and quantifying the eluting cross-reacting cannabinoids with radioimmunoassay. It has been applied to the analysis of cannabinoids in human urine obtained from subjects who had smoked delta 9-tetrahydrocannabinol and the identities of some of the cross-reacting cannabinoids have been established by gas chromatography-mass spectrometry. The method is suitable for use as a routine procedure for cannabinoid analysis in urine."}
{"id": "PMID:232709", "title": "[Variability of the relay neurons in the corpus geniculatum laterale, pars dorsalis in the albino rat].", "content": "38 Golgi-impregnated relay cells from the Wistar rat's dLGN were investigated considering their possible differentiation into 2 types using camera lucida drawings with a magnification of 800. The following criteria were taken into account: 1. size of neurons (perikarya, size of dendritic domains) 2. structure of dendrites (number of dendrites, branching points, distribution of dendritic density in relation to the perikaryon, surface structures of dendrites). It was tried to correlate the investigated parameters quantitatively and qualitatively. The results showed that inspite of a missing clear subdivision into 2 types there exists a trend towards developing a second type of relay cells.", "contents": "[Variability of the relay neurons in the corpus geniculatum laterale, pars dorsalis in the albino rat]. 38 Golgi-impregnated relay cells from the Wistar rat's dLGN were investigated considering their possible differentiation into 2 types using camera lucida drawings with a magnification of 800. The following criteria were taken into account: 1. size of neurons (perikarya, size of dendritic domains) 2. structure of dendrites (number of dendrites, branching points, distribution of dendritic density in relation to the perikaryon, surface structures of dendrites). It was tried to correlate the investigated parameters quantitatively and qualitatively. The results showed that inspite of a missing clear subdivision into 2 types there exists a trend towards developing a second type of relay cells."}
{"id": "PMID:232710", "title": "[Nuclear spheroids in neurons of the human hypothalamus].", "content": "Morphological structure, distribution and frequency of the so-called \"nuclear spheroids\" have been studied in the human hypothalamus. The following results were obtained: 1. By light microscopy, the nuclear spheroids turned out to be small or large spheroid bodies inside the nucleus. They are almost homogeneous, rarely granular, vacuolar or reticular and occasionally they are multiple. They are best stained with the cresyl-violet technique. They do not exhibit any histochemical pecularities. Aside from typical nuclear spheroids, irregularly shaped nuclei were frequently seen, associated with increased nuclear folds, transitional stages between nuclear folds and nuclear spheroids were also present. Certain microscopic features suggest invagination and displacement of nuclear membrane and cytoplasm into the karyoplasma. 2. By electron microscopy, the nuclear spheroids consist of nuclear membranes and cytoplasmic constituents. They, therefore, actually represent cytoplasm protruding into the cell nucleus. 3. The nuclear spheroids occur almost regularly and most frequently in the ventromedial field of the tuber cinereum, foremost in the infundibular (= arcuate) nucleus. They numerically increase during life. They are rarely found in the ventromedial nucleus but do occur in most of the adults. In the paraventricular nucleus, the supraoptic nucleus, the lateral nuclei tuberis, and in lateral hypothalamic nucleus, they are found by far less often. They scarcely develop in the preoptic area, in the dorsal field, in the tubero-mamillar complex, in the parafornical nuclear groups, in the premamillary nucleus and in the mamillary nuclei. 4. Within the infundibular (= arcuate) nucleus, the nuclear spheroids are particularly numerous in the basal and basolateral regions, whose neurons, under certain functional conditions--such as the Sheedan syndrome, in the menopause and in association with pituitary neoplasms-, appear hypertrophic. Within the hypertrophic neurons of this region, which we designate the subventricular part of the infundibular nucleus, nuclear spheroids are definitely more frequent, and they are of the large type. 5. A separation of the subventricular part based on the distributional pattern of the nuclear spheroids indicates a pathological karyoarchitectonics which supplements the normal karyoarchitectonics (Bachmann, 1948). 6. The nuclear spheroids seem to be associated with increased neuronal activities, for their frequently strongly correlates with the neuronal hypertrophy which expresses enhanced neuroendocrinological activity.", "contents": "[Nuclear spheroids in neurons of the human hypothalamus]. Morphological structure, distribution and frequency of the so-called \"nuclear spheroids\" have been studied in the human hypothalamus. The following results were obtained: 1. By light microscopy, the nuclear spheroids turned out to be small or large spheroid bodies inside the nucleus. They are almost homogeneous, rarely granular, vacuolar or reticular and occasionally they are multiple. They are best stained with the cresyl-violet technique. They do not exhibit any histochemical pecularities. Aside from typical nuclear spheroids, irregularly shaped nuclei were frequently seen, associated with increased nuclear folds, transitional stages between nuclear folds and nuclear spheroids were also present. Certain microscopic features suggest invagination and displacement of nuclear membrane and cytoplasm into the karyoplasma. 2. By electron microscopy, the nuclear spheroids consist of nuclear membranes and cytoplasmic constituents. They, therefore, actually represent cytoplasm protruding into the cell nucleus. 3. The nuclear spheroids occur almost regularly and most frequently in the ventromedial field of the tuber cinereum, foremost in the infundibular (= arcuate) nucleus. They numerically increase during life. They are rarely found in the ventromedial nucleus but do occur in most of the adults. In the paraventricular nucleus, the supraoptic nucleus, the lateral nuclei tuberis, and in lateral hypothalamic nucleus, they are found by far less often. They scarcely develop in the preoptic area, in the dorsal field, in the tubero-mamillar complex, in the parafornical nuclear groups, in the premamillary nucleus and in the mamillary nuclei. 4. Within the infundibular (= arcuate) nucleus, the nuclear spheroids are particularly numerous in the basal and basolateral regions, whose neurons, under certain functional conditions--such as the Sheedan syndrome, in the menopause and in association with pituitary neoplasms-, appear hypertrophic. Within the hypertrophic neurons of this region, which we designate the subventricular part of the infundibular nucleus, nuclear spheroids are definitely more frequent, and they are of the large type. 5. A separation of the subventricular part based on the distributional pattern of the nuclear spheroids indicates a pathological karyoarchitectonics which supplements the normal karyoarchitectonics (Bachmann, 1948). 6. The nuclear spheroids seem to be associated with increased neuronal activities, for their frequently strongly correlates with the neuronal hypertrophy which expresses enhanced neuroendocrinological activity."}
{"id": "PMID:232711", "title": "Biological standards for energy dispersive x-ray analysis.", "content": "Biological standards containing known concentrations of crystalline silica were prepared for x-ray energy spectrometry (XES) using homogenized tissue and gelatin. Sections of 7 micrometer thickness were cut, air dried, carbon coated, and analyzed by XES. All sections containing crystalline silica generated x-ray counts on a linear relationship with increasing concentrations of silica in the standards. However, tissue sections containing identical concentrations of silica generated x-ray counts approximately 50 percent lower than gelatin sections. Gelatin sections showed considerable shrinkage during drying which may have influenced x-ray generation. The combined effects of elements present in the biological system and high density of tissues also may have contributed to the lower XES counts. These results stress the importance of using standards identical to specimens undergoing XES analysis.", "contents": "Biological standards for energy dispersive x-ray analysis. Biological standards containing known concentrations of crystalline silica were prepared for x-ray energy spectrometry (XES) using homogenized tissue and gelatin. Sections of 7 micrometer thickness were cut, air dried, carbon coated, and analyzed by XES. All sections containing crystalline silica generated x-ray counts on a linear relationship with increasing concentrations of silica in the standards. However, tissue sections containing identical concentrations of silica generated x-ray counts approximately 50 percent lower than gelatin sections. Gelatin sections showed considerable shrinkage during drying which may have influenced x-ray generation. The combined effects of elements present in the biological system and high density of tissues also may have contributed to the lower XES counts. These results stress the importance of using standards identical to specimens undergoing XES analysis."}
{"id": "PMID:232714", "title": "Effects of pesticides on 3H-dihydrotestosterone binding to cytosol proteins from various tissues of the mouse.", "content": "These in vitro studies, utilizing cytosols prepared from various tissues (viz. anterior prostate gland, seminal vesicle, kidney and liver) taken from mice 3 days post-castration, were undertaken in order to determine whether or not certain pesticides could alter the binding of 3H-DHT to cytosolic androgen binding components. Estrone, cyproterone acetate, and unlabeled DHT were employed to confirm the presence of specific 3H-DHT binding components in the cytosols. The effects of various pesticides on 3H-DHT binding in these tissue cytosols were then assessed. Parathion (10(-8)--10(-5) M) was found to be an effective inhibitor of total 3H-DHT binding in the prostate, seminal veiscle, kidney and liver. This organophosphate was unable to compete with 3H-DHT for cytosol binding sites in the intestine. Similar in vitro binding studies using dieldrin, DDT, or carbaryl failed to reveal any interference with 3H-DHT binding in any of the tissue studied. The mechanism of parathion's interference with 3H-DHT binding is unclear.", "contents": "Effects of pesticides on 3H-dihydrotestosterone binding to cytosol proteins from various tissues of the mouse. These in vitro studies, utilizing cytosols prepared from various tissues (viz. anterior prostate gland, seminal vesicle, kidney and liver) taken from mice 3 days post-castration, were undertaken in order to determine whether or not certain pesticides could alter the binding of 3H-DHT to cytosolic androgen binding components. Estrone, cyproterone acetate, and unlabeled DHT were employed to confirm the presence of specific 3H-DHT binding components in the cytosols. The effects of various pesticides on 3H-DHT binding in these tissue cytosols were then assessed. Parathion (10(-8)--10(-5) M) was found to be an effective inhibitor of total 3H-DHT binding in the prostate, seminal veiscle, kidney and liver. This organophosphate was unable to compete with 3H-DHT for cytosol binding sites in the intestine. Similar in vitro binding studies using dieldrin, DDT, or carbaryl failed to reveal any interference with 3H-DHT binding in any of the tissue studied. The mechanism of parathion's interference with 3H-DHT binding is unclear."}
{"id": "PMID:232715", "title": "Clinical aspects of gut enzymology.", "content": "Enzymological alterations in functional disturbances and in diseases of the intestine are reviewed. Examples are given for diagnostic significance (e.g. in Hirschsprung's and Crohn's diseases), for pathogenetic considerations (e.g. in hypolactasia and in celiac disease), and for secondary involvement of the liver (e.g. in intestinal tumors and after bypass surgery) and are discussed in more detail.", "contents": "Clinical aspects of gut enzymology. Enzymological alterations in functional disturbances and in diseases of the intestine are reviewed. Examples are given for diagnostic significance (e.g. in Hirschsprung's and Crohn's diseases), for pathogenetic considerations (e.g. in hypolactasia and in celiac disease), and for secondary involvement of the liver (e.g. in intestinal tumors and after bypass surgery) and are discussed in more detail."}
{"id": "PMID:232718", "title": "Modulation of transmission at a glutamate synapse.", "content": "The amino acid L-aspartate markedly potentiates the responses elicited by L-glutamate at excitatory neuromuscular synapses in lobster walking limbs. Results are consistent with the idea that aspartate increases the affinity between glutamate and its binding sites in the postsynaptic receptor. Although complications due to release from other amino acid sources are a serious qualification, studies of neurally induced release of glutamate and aspartate suggest that both amino acids are released from excitatory nerve terminals. Experiments comparing the potentiating action of a variety of amino acids with their ability to inhibit glutamate uptake are not supportive of the notion that inhibition of agonist removal is the primary mode of action in the potentiation process. However, this idea, as well as the suggestion that aspartate may induce release of glutamate from extrajunctional entrapment sites, are not ruled out. Indeed, it is likely that the modulatory process embodies a multiplicity of reactions with given ones dominating from preparation to preparation.", "contents": "Modulation of transmission at a glutamate synapse. The amino acid L-aspartate markedly potentiates the responses elicited by L-glutamate at excitatory neuromuscular synapses in lobster walking limbs. Results are consistent with the idea that aspartate increases the affinity between glutamate and its binding sites in the postsynaptic receptor. Although complications due to release from other amino acid sources are a serious qualification, studies of neurally induced release of glutamate and aspartate suggest that both amino acids are released from excitatory nerve terminals. Experiments comparing the potentiating action of a variety of amino acids with their ability to inhibit glutamate uptake are not supportive of the notion that inhibition of agonist removal is the primary mode of action in the potentiation process. However, this idea, as well as the suggestion that aspartate may induce release of glutamate from extrajunctional entrapment sites, are not ruled out. Indeed, it is likely that the modulatory process embodies a multiplicity of reactions with given ones dominating from preparation to preparation."}
{"id": "PMID:232719", "title": "Excitatory amino acid receptors and synaptic excitation in the mammalian central nervous system.", "content": "At least two different types of excitatory amino acid receptors have been identified in the mammalian and amphibian central nervous systems. One type ('NMDA receptors') appears to be important in amino acid-mediated synaptic excitation, NMDA being the most potent and specific exogenous agonist for this type of receptor. Many antagonists have selective blocking actions at these NMDA receptors, and such substances are also selective antagonists of synaptic excitation in the vertebrate spinal cord. It is proposed that these receptors are transmitter receptors activated by an excitatory amino acid. In addition, extrasynaptic receptors, activated by domoate, kainate, quisqualate and L-glutamate, but not by NMDA, and only weakly by L-aspartate, have been identified on dorsal root fibres of the immature rat.", "contents": "Excitatory amino acid receptors and synaptic excitation in the mammalian central nervous system. At least two different types of excitatory amino acid receptors have been identified in the mammalian and amphibian central nervous systems. One type ('NMDA receptors') appears to be important in amino acid-mediated synaptic excitation, NMDA being the most potent and specific exogenous agonist for this type of receptor. Many antagonists have selective blocking actions at these NMDA receptors, and such substances are also selective antagonists of synaptic excitation in the vertebrate spinal cord. It is proposed that these receptors are transmitter receptors activated by an excitatory amino acid. In addition, extrasynaptic receptors, activated by domoate, kainate, quisqualate and L-glutamate, but not by NMDA, and only weakly by L-aspartate, have been identified on dorsal root fibres of the immature rat."}
{"id": "PMID:232720", "title": "High-affinity binding processes for GABA, glycine, and beta-alanine in synaptosome-enriched fractions of rats CNS.", "content": "A bicuculline-sensitive component of the binding of GABA and strychnine-sensitive components of the binding of glycine and beta alanine to synaptosome-enriched fractions of rat CNS have been demonstrated in the presence of physiological concentrations of Na+ and other inorganic ions. These processes might be related to synaptic receptors for these inhibitory amino-acids.", "contents": "High-affinity binding processes for GABA, glycine, and beta-alanine in synaptosome-enriched fractions of rats CNS. A bicuculline-sensitive component of the binding of GABA and strychnine-sensitive components of the binding of glycine and beta alanine to synaptosome-enriched fractions of rat CNS have been demonstrated in the presence of physiological concentrations of Na+ and other inorganic ions. These processes might be related to synaptic receptors for these inhibitory amino-acids."}
{"id": "PMID:232721", "title": "The depolarizing responses to GABA in rat sensory ganglia in vivo and in vitro. A study of the role of glial uptake.", "content": "Intracellular recordings of neurones in dorsal root ganglia (DRG) have demonstrated that GABA transport into DRG satellite cell does not affect neuronal responses to this amino acid. The experiments were performed with transport-resistant GABA analogues and with inhibition of GABA uptake. GABA response characteristics can thus be considered exclusively neuronal in origin.", "contents": "The depolarizing responses to GABA in rat sensory ganglia in vivo and in vitro. A study of the role of glial uptake. Intracellular recordings of neurones in dorsal root ganglia (DRG) have demonstrated that GABA transport into DRG satellite cell does not affect neuronal responses to this amino acid. The experiments were performed with transport-resistant GABA analogues and with inhibition of GABA uptake. GABA response characteristics can thus be considered exclusively neuronal in origin."}
{"id": "PMID:232722", "title": "Distribution of gaba-receptors and gaba-carriers in the mammalian nervous system.", "content": "1. Extrasynaptic GABA-receptors occur on both neurone somata and unmyelinated axons in the mammalian peripheral nervous system. Activation of these receptors leads to depolarization, reduced spike amplitude and slowed conduction, probably mediated through increased Cl- conductance. 2. GABA also depolarizeds preganglionic nerve terminals in the rat superior cervical ganglion and reduces the release of acetylcholine by preganglionic nerve impulses. 3. The Schwann and satellite neuroglial cells surrounding peripheral unmyelinated axons and neurones possess a GABA-carrier promoting net uptake of GABA at external concentrations greater than or equal to 1 microM. 4. The possible significance of extrasynaptic receptors and carriers for GABA is discussed.", "contents": "Distribution of gaba-receptors and gaba-carriers in the mammalian nervous system. 1. Extrasynaptic GABA-receptors occur on both neurone somata and unmyelinated axons in the mammalian peripheral nervous system. Activation of these receptors leads to depolarization, reduced spike amplitude and slowed conduction, probably mediated through increased Cl- conductance. 2. GABA also depolarizeds preganglionic nerve terminals in the rat superior cervical ganglion and reduces the release of acetylcholine by preganglionic nerve impulses. 3. The Schwann and satellite neuroglial cells surrounding peripheral unmyelinated axons and neurones possess a GABA-carrier promoting net uptake of GABA at external concentrations greater than or equal to 1 microM. 4. The possible significance of extrasynaptic receptors and carriers for GABA is discussed."}
{"id": "PMID:232723", "title": "[The monoamines in molluscs. II. Dopamine and neurotransmission. Cardiac dopaminergic innervation in Helix pomatia (author's transl)].", "content": "In the molluscs, dopamine is very probably a chemical transmitter at the level of both the central nervous system and certain peripheral structures. The heart of Helix pomatia does not have any intrinsic innervation, but it receives extrinsic innervation from fibres coming from the visceral nerve. Formaldehyde fluorescence histochemistry localizes the cardiac catecholamines in some of these fibres and in their endings. However, dopamine, which dominates, does not seem to be a transmitter involved in cardioregulation in the same way as 5-hydroxytryptamine. The quantities of active dopamine (stimulants) cannot be compared with those required for a neurotransmitter. This is also true for noradrenaline. Dopamine more certainly plays a role at the metabolic and tropic level by acting within a more or less short period as a regulator of cellular activity and contractility. The Helix heart is a suitable model for future research in this field.", "contents": "[The monoamines in molluscs. II. Dopamine and neurotransmission. Cardiac dopaminergic innervation in Helix pomatia (author's transl)]. In the molluscs, dopamine is very probably a chemical transmitter at the level of both the central nervous system and certain peripheral structures. The heart of Helix pomatia does not have any intrinsic innervation, but it receives extrinsic innervation from fibres coming from the visceral nerve. Formaldehyde fluorescence histochemistry localizes the cardiac catecholamines in some of these fibres and in their endings. However, dopamine, which dominates, does not seem to be a transmitter involved in cardioregulation in the same way as 5-hydroxytryptamine. The quantities of active dopamine (stimulants) cannot be compared with those required for a neurotransmitter. This is also true for noradrenaline. Dopamine more certainly plays a role at the metabolic and tropic level by acting within a more or less short period as a regulator of cellular activity and contractility. The Helix heart is a suitable model for future research in this field."}
{"id": "PMID:232724", "title": "[Protein metabolism and sensitivity to tetrodotoxin of cardiomyoblasts cultured in vitro. Influence of insulin (author's transl)].", "content": "1. Insulin prevents the decrease in sensitivity to tetrodotoxin in populations of embryonic cardiomyoblasts cultured in vitro. This effect of insulin remains when the hormone is added to the culture medium up to 16 hours after the beginning of the culture. 2. Amino-acid deprivation results in an acceleration of the loss of sensitivity to tetrodotoxin in cultured cardiomyoblasts. Addition of cycloheximide, an inhibitor of protein synthesis, has the same effect. These results suggest that the sensitivity to tetrodotoxin of the cardiac cells depends on aspects of protein metabolism which can be controlled by insulin. 3. Return of the cell population to a culture medium containing amino acids and serum or insulin after 7 hours of culture in an amino acid free medium induces a striking increase in the percentage of cardiac cells sensitive to tetrodotoxin. This sensitivity to the inhibitor of the fast sodium carrying mechanism appears to be an element of the pleiotypic response of the cells in culture to serum or to insulin.", "contents": "[Protein metabolism and sensitivity to tetrodotoxin of cardiomyoblasts cultured in vitro. Influence of insulin (author's transl)]. 1. Insulin prevents the decrease in sensitivity to tetrodotoxin in populations of embryonic cardiomyoblasts cultured in vitro. This effect of insulin remains when the hormone is added to the culture medium up to 16 hours after the beginning of the culture. 2. Amino-acid deprivation results in an acceleration of the loss of sensitivity to tetrodotoxin in cultured cardiomyoblasts. Addition of cycloheximide, an inhibitor of protein synthesis, has the same effect. These results suggest that the sensitivity to tetrodotoxin of the cardiac cells depends on aspects of protein metabolism which can be controlled by insulin. 3. Return of the cell population to a culture medium containing amino acids and serum or insulin after 7 hours of culture in an amino acid free medium induces a striking increase in the percentage of cardiac cells sensitive to tetrodotoxin. This sensitivity to the inhibitor of the fast sodium carrying mechanism appears to be an element of the pleiotypic response of the cells in culture to serum or to insulin."}
{"id": "PMID:232725", "title": "[Comparison of the effects of analgesia-producing peripheral and central stimulations in cats. Effect of nalorphine (author's transl)].", "content": "The effects of weak intensity percutaneous peripheral stimulations (SPPc) on the transmission of nociceptive messages induced by stimulation of the dental pulp have been studied on anaesthetized cats. 1. The jaw opening reflex (ROG) and the evoked potentials in the thalamic center median (CM), by stimulation of the dental pulp, disappear after a mean of 30 min after the start of SPPc. 2. These effects are analogous to those obtained by stimulation of the periaqueductal gray matter (St.GC) or by I.V. morphine injection. 3. The I.V. injection of the morphine antagonist (Nalorphine) blocks both the effects of the SPPc and those of the St.GC. 4. The authors put forth the hypothesis of a common mechanism of action of the SPPc and the St.GC which, through the liberation of endogenous morphinomimetic substances, would activate descending inhibitor impulses.", "contents": "[Comparison of the effects of analgesia-producing peripheral and central stimulations in cats. Effect of nalorphine (author's transl)]. The effects of weak intensity percutaneous peripheral stimulations (SPPc) on the transmission of nociceptive messages induced by stimulation of the dental pulp have been studied on anaesthetized cats. 1. The jaw opening reflex (ROG) and the evoked potentials in the thalamic center median (CM), by stimulation of the dental pulp, disappear after a mean of 30 min after the start of SPPc. 2. These effects are analogous to those obtained by stimulation of the periaqueductal gray matter (St.GC) or by I.V. morphine injection. 3. The I.V. injection of the morphine antagonist (Nalorphine) blocks both the effects of the SPPc and those of the St.GC. 4. The authors put forth the hypothesis of a common mechanism of action of the SPPc and the St.GC which, through the liberation of endogenous morphinomimetic substances, would activate descending inhibitor impulses."}
{"id": "PMID:232728", "title": "Effects of cortisone on mechanical activity and membrane ionic currents in frog auricular fibres.", "content": "The influence of cortisone on the mechanical and electrical activity of frog auricular fibres was investigated under voltage clamp conditions. 1. Cortisone exerted in vitro an inotropic action depending on concentration; a maximal positive inotropic effect was observed with 2 x 10(-4) g/ml of cortisone. 2. The positive inotropic effect of cortisone might be either an indirect sympathomimetic effect or an adrenaline-like effect. 3. The positive inotropic action of cortisone was correlated with modifications of the cardiac action potential: the amplitude of the action potential was enhanced while the resting membrane potential was unchanged; the amplitude and duration of the plateau were increased and the duration of the action potential was lengthened. 4. The electrical changes were related to an increase in the slow calcium current intensity resulting from an increase in the slow calcium conductance.", "contents": "Effects of cortisone on mechanical activity and membrane ionic currents in frog auricular fibres. The influence of cortisone on the mechanical and electrical activity of frog auricular fibres was investigated under voltage clamp conditions. 1. Cortisone exerted in vitro an inotropic action depending on concentration; a maximal positive inotropic effect was observed with 2 x 10(-4) g/ml of cortisone. 2. The positive inotropic effect of cortisone might be either an indirect sympathomimetic effect or an adrenaline-like effect. 3. The positive inotropic action of cortisone was correlated with modifications of the cardiac action potential: the amplitude of the action potential was enhanced while the resting membrane potential was unchanged; the amplitude and duration of the plateau were increased and the duration of the action potential was lengthened. 4. The electrical changes were related to an increase in the slow calcium current intensity resulting from an increase in the slow calcium conductance."}
{"id": "PMID:232732", "title": "[Collagenase inhibition: an experiment in the treatment of scleromalacia perforans (author's transl)].", "content": "Report on local application of Cystin eye drops in a case of scleromalacia perforans. This medication brought the necrotizing disease process to a standstill. There was even discrete neoformation of scleral tissue, which we attribute to the collagenase inhibiting action of this drug.", "contents": "[Collagenase inhibition: an experiment in the treatment of scleromalacia perforans (author's transl)]. Report on local application of Cystin eye drops in a case of scleromalacia perforans. This medication brought the necrotizing disease process to a standstill. There was even discrete neoformation of scleral tissue, which we attribute to the collagenase inhibiting action of this drug."}
{"id": "PMID:232733", "title": "[Corneal deposits in children on dialysis and treatment with vitamin D3 and 1,25 DHCC (author's transl)].", "content": "The corneas of 15 children on intermittent long-term dialysis for renal failure were studied, first during a period of treatment with high doses of vitamin D3 and subsequently during a study with the vitamin D metabolite 1,25 DHCC. Metastatic calcification of the limbus or increased limbic deposits only occurred during the second treatment phase, with vitamin 1,25 DHCC. In 5 of these children phases with plasma calcium levels were recorded which were closely related to the times when corneal changes occurred. In 3 children phosphate values were also increased. Only one child presented with normal calcium values and merely an increase in phosphate concentration. Regression of corneal deposits following normalization of calcium metabolism seems possible in the light of observations so far.", "contents": "[Corneal deposits in children on dialysis and treatment with vitamin D3 and 1,25 DHCC (author's transl)]. The corneas of 15 children on intermittent long-term dialysis for renal failure were studied, first during a period of treatment with high doses of vitamin D3 and subsequently during a study with the vitamin D metabolite 1,25 DHCC. Metastatic calcification of the limbus or increased limbic deposits only occurred during the second treatment phase, with vitamin 1,25 DHCC. In 5 of these children phases with plasma calcium levels were recorded which were closely related to the times when corneal changes occurred. In 3 children phosphate values were also increased. Only one child presented with normal calcium values and merely an increase in phosphate concentration. Regression of corneal deposits following normalization of calcium metabolism seems possible in the light of observations so far."}
{"id": "PMID:232735", "title": "Role of the microfibrillar system in knob action of transformed cells.", "content": "Transformed cells often display knobs (or blebs) distributed over their surface throughout most of interphase. Scanning electron microscopy (SEM) and time-lapse cinematography on CHO-K1 cells reveal roughly spherical knobs of 0.5-4 micron in diameter distributed densely around the cell periphery but sparsely over the central, nuclear hillock and oscillating in and out of the membrane with a period of 15-60 sec. Cyclic AMP derivatives cause the phenomenon of reverse transformation, in which the cell is converted to a fibroblastic morphology with disappearance of the knobs. A model was proposed attributing knob formation to the disorganization of the jointly operating microtubular and microfilamentous structure of the normal fibroblast. Evidence for this model includes the following: 1) Either colcemid or cytochalasin B (CB) prevents the knob disappearance normally produced by cAMP, and can elicit similar knobs from smooth-surfaced cells; 2) knob removal by cAMP is specific, with little effect on microvilli and lamellipodia; 3) immunofluorescence with antiactin sera reveals condensed, amorphous masses directly beneath the membrane of CB-treated cells instead of smooth, parallel fibrous patterns of reverse-transformed cells or normal fibroblasts; 4) transmission electron microscopy (TEM) of sections show dense, elongated microfilament bundles and microtubules parallel to the long axis of the reverse-transformed CHO cell, but sparse, random microtubules throughout the transformed cell and an apparent disordered network of 6-nm microfilaments beneath the knobs; 5) cell membranes at the end of telophase, when the spindle disappears and cleavage is complete, display typical knob activity as expected by this picture.", "contents": "Role of the microfibrillar system in knob action of transformed cells. Transformed cells often display knobs (or blebs) distributed over their surface throughout most of interphase. Scanning electron microscopy (SEM) and time-lapse cinematography on CHO-K1 cells reveal roughly spherical knobs of 0.5-4 micron in diameter distributed densely around the cell periphery but sparsely over the central, nuclear hillock and oscillating in and out of the membrane with a period of 15-60 sec. Cyclic AMP derivatives cause the phenomenon of reverse transformation, in which the cell is converted to a fibroblastic morphology with disappearance of the knobs. A model was proposed attributing knob formation to the disorganization of the jointly operating microtubular and microfilamentous structure of the normal fibroblast. Evidence for this model includes the following: 1) Either colcemid or cytochalasin B (CB) prevents the knob disappearance normally produced by cAMP, and can elicit similar knobs from smooth-surfaced cells; 2) knob removal by cAMP is specific, with little effect on microvilli and lamellipodia; 3) immunofluorescence with antiactin sera reveals condensed, amorphous masses directly beneath the membrane of CB-treated cells instead of smooth, parallel fibrous patterns of reverse-transformed cells or normal fibroblasts; 4) transmission electron microscopy (TEM) of sections show dense, elongated microfilament bundles and microtubules parallel to the long axis of the reverse-transformed CHO cell, but sparse, random microtubules throughout the transformed cell and an apparent disordered network of 6-nm microfilaments beneath the knobs; 5) cell membranes at the end of telophase, when the spindle disappears and cleavage is complete, display typical knob activity as expected by this picture."}
{"id": "PMID:232736", "title": "Alteration of human breast tumor cell membrane functions by chromosome-mediated gene transfer.", "content": "BOT-2 cells (human breast tumor origin) have an impaired ability to utilize exogenous thymidine. Previous studies revealed this deficiency to be the permeation event rather than phosphorylation, since the cells have active thymidine kinase. Chromosome-mediated gene transfer was used to transfer genetic information in the form of metaphase chromosomes, from HeLa-65 cells to the BOT-2 cells, correcting the permease deficiency. Poly-L-ornithine or lipochromes were used for facilitation of chromosome uptake. After selection on HAT medium, transferant clones were isolated at a frequency of 4 x 10(-5) and 1 x 10(-5), respectively. Transferants MGP-1 and MGL-1 are stable after 18 months and have been characterized on the bases of purine and pyrimidine nucleoside uptake, relative thymidine kinase activities, alkaline phosphatase activities, and hydrocortisone-induced alkaline phosphatase activity. MGP-1 demonstrates positive thymidine uptake and incorporates radiolabeled thymidine into DNA. MGL-1 remains thymidine transport-deficient and surveys on HAT by increasing endogenous dihydrofolate reductase activity. Alkaline phosphatase activity in MGL-1 is similar to HeLa-65, 2% of that in BOT-2, and in addition, is inducible 25-30-fold by 3 micro M hydrocortisone. We have separated, genetically, a thymidine permease function from phosphorylation in cells of human origin and have transferred genetic information for the regulation of alkaline phosphatase.", "contents": "Alteration of human breast tumor cell membrane functions by chromosome-mediated gene transfer. BOT-2 cells (human breast tumor origin) have an impaired ability to utilize exogenous thymidine. Previous studies revealed this deficiency to be the permeation event rather than phosphorylation, since the cells have active thymidine kinase. Chromosome-mediated gene transfer was used to transfer genetic information in the form of metaphase chromosomes, from HeLa-65 cells to the BOT-2 cells, correcting the permease deficiency. Poly-L-ornithine or lipochromes were used for facilitation of chromosome uptake. After selection on HAT medium, transferant clones were isolated at a frequency of 4 x 10(-5) and 1 x 10(-5), respectively. Transferants MGP-1 and MGL-1 are stable after 18 months and have been characterized on the bases of purine and pyrimidine nucleoside uptake, relative thymidine kinase activities, alkaline phosphatase activities, and hydrocortisone-induced alkaline phosphatase activity. MGP-1 demonstrates positive thymidine uptake and incorporates radiolabeled thymidine into DNA. MGL-1 remains thymidine transport-deficient and surveys on HAT by increasing endogenous dihydrofolate reductase activity. Alkaline phosphatase activity in MGL-1 is similar to HeLa-65, 2% of that in BOT-2, and in addition, is inducible 25-30-fold by 3 micro M hydrocortisone. We have separated, genetically, a thymidine permease function from phosphorylation in cells of human origin and have transferred genetic information for the regulation of alkaline phosphatase."}
{"id": "PMID:232737", "title": "[Urinary excretion of cAMP after PTH injection in patients with hypohyperparathyroidism (author's transl)].", "content": "The urinary excretion of cyclic adenosine monophosphate (cAMP) and phosphate in response to an intravenous injection of 200 U.I. PTH in two women with hypohyperparathyroidism was studied. PTH activity was previously verified. Both patients were under treatment with vitamin D and their plasma calcium and phosphate levels were normal at the time of the study. Basal values for urinary excretion of cAMP were 2.25 nmol/min in one patient and 4.2 nmol/min in the other. Maximum excretion after PTH injection were 6.4 nmol/min and 5.5 nmol/min respectively. Basal values for urinary excretion of phosphate were 0.32 mg/min in the first patient and 0.18 mg/min in the second. After PTH injection the peak values were 0.73 mg/min and 0.35 mg/min respectively. These results pointed out the existence of a renal resistance to PTH which, unlike what happens in other similar patients, cannot be corrected with the administration of vitamin D.", "contents": "[Urinary excretion of cAMP after PTH injection in patients with hypohyperparathyroidism (author's transl)]. The urinary excretion of cyclic adenosine monophosphate (cAMP) and phosphate in response to an intravenous injection of 200 U.I. PTH in two women with hypohyperparathyroidism was studied. PTH activity was previously verified. Both patients were under treatment with vitamin D and their plasma calcium and phosphate levels were normal at the time of the study. Basal values for urinary excretion of cAMP were 2.25 nmol/min in one patient and 4.2 nmol/min in the other. Maximum excretion after PTH injection were 6.4 nmol/min and 5.5 nmol/min respectively. Basal values for urinary excretion of phosphate were 0.32 mg/min in the first patient and 0.18 mg/min in the second. After PTH injection the peak values were 0.73 mg/min and 0.35 mg/min respectively. These results pointed out the existence of a renal resistance to PTH which, unlike what happens in other similar patients, cannot be corrected with the administration of vitamin D."}
{"id": "PMID:232738", "title": "[The usefulness of the quantitative evaluation of the plasma levels of the carcinoembryonic antigen (CEA) in patients with respiratory neoplasms (author's transl)].", "content": "Plasma concentration of the carcinoembryonic antigen (CEA) was determined by radioimmunoassay in 80 patients affected with different neoplasms of the respiratory system, among which the most predominant was bronchial carcinoma. For this type of tumor the results showed a percentage of positivity of 69 percent, with a greater value in the disseminated neoplasias (81 percent) in comparison with those which were localized (48 percent). The concentrations of the antigen were greater in the metastatic tumors; in 55 percent of the cases levels above 40 ng/ml were observed. On the other hand this figure was reached only by 4 percent of the localized tumors. Values of the antigen higher than 40 ng/ml should lead to the suspicion of the existence of neoplastic widespread. Among the rest of the series the negativity noticed in all the cases of pleural mesothelioma stands out, and indicates that this type of tumors does not produce CEA.", "contents": "[The usefulness of the quantitative evaluation of the plasma levels of the carcinoembryonic antigen (CEA) in patients with respiratory neoplasms (author's transl)]. Plasma concentration of the carcinoembryonic antigen (CEA) was determined by radioimmunoassay in 80 patients affected with different neoplasms of the respiratory system, among which the most predominant was bronchial carcinoma. For this type of tumor the results showed a percentage of positivity of 69 percent, with a greater value in the disseminated neoplasias (81 percent) in comparison with those which were localized (48 percent). The concentrations of the antigen were greater in the metastatic tumors; in 55 percent of the cases levels above 40 ng/ml were observed. On the other hand this figure was reached only by 4 percent of the localized tumors. Values of the antigen higher than 40 ng/ml should lead to the suspicion of the existence of neoplastic widespread. Among the rest of the series the negativity noticed in all the cases of pleural mesothelioma stands out, and indicates that this type of tumors does not produce CEA."}
{"id": "PMID:232739", "title": "[Bulk vegetable material in human nutrition (author's transl)].", "content": "Intake of bulk vegetable material has diminished in the western countries considerably since the beginning of industrialisation. Lack of bulk substances is being held responsible lately for the increase of diseases of the gastrointestinal tract. It has been shown, that bulk materials increased stool weight and decreased gastrointestinal passage time; it is assumed, that they do have beneficial effects in the treatment of diverticulosis of the colon. It is still controversial, how bulk materials influence mineral metabolism, especially intestinal resorption of iron, calcium and other bivalent cations. Hypocholesterinemic effects of lignin and pectin, which form part of vegetable bulk food, are as yet not well defined. The question is still open, if bulk foods do have prophylactic effects in regard to carcinoma of the colon.", "contents": "[Bulk vegetable material in human nutrition (author's transl)]. Intake of bulk vegetable material has diminished in the western countries considerably since the beginning of industrialisation. Lack of bulk substances is being held responsible lately for the increase of diseases of the gastrointestinal tract. It has been shown, that bulk materials increased stool weight and decreased gastrointestinal passage time; it is assumed, that they do have beneficial effects in the treatment of diverticulosis of the colon. It is still controversial, how bulk materials influence mineral metabolism, especially intestinal resorption of iron, calcium and other bivalent cations. Hypocholesterinemic effects of lignin and pectin, which form part of vegetable bulk food, are as yet not well defined. The question is still open, if bulk foods do have prophylactic effects in regard to carcinoma of the colon."}
{"id": "PMID:232742", "title": "Malignant pheochromocytoma in childhood: report of a case with familial neurofibromatosis.", "content": "A 14-year-old male with familial neurofibromatosis and widely disseminated malignant pheochromocytoma is described. Current criteria for the diagnosis and management of this rare malignancy are discussed.", "contents": "Malignant pheochromocytoma in childhood: report of a case with familial neurofibromatosis. A 14-year-old male with familial neurofibromatosis and widely disseminated malignant pheochromocytoma is described. Current criteria for the diagnosis and management of this rare malignancy are discussed."}
{"id": "PMID:232744", "title": "Serum phosphodiesterase I activity in breast cancer patients.", "content": "Serum phosphodiesterase I (PDE I) activity was determined in 13 control and 51 breast-cancer patients with various stages of disease. Patients with both localized and metastatic breast cancer had significantly elevated serum PDE I activity. The highest activity was seen in patients with liver metastases. A decline in serum PDE I activity was seen after surgical resection of all known disease.", "contents": "Serum phosphodiesterase I activity in breast cancer patients. Serum phosphodiesterase I (PDE I) activity was determined in 13 control and 51 breast-cancer patients with various stages of disease. Patients with both localized and metastatic breast cancer had significantly elevated serum PDE I activity. The highest activity was seen in patients with liver metastases. A decline in serum PDE I activity was seen after surgical resection of all known disease."}
{"id": "PMID:232750", "title": "[(Gynecomastia as precancerous lesion: aspiration biopsy cytology and its histology)].", "content": "In 19 of 39 patients suffering from gynecomastia, between 1967 and 1979 aspiration biopsy cytology and surgery was performed by the author. Atypia and precancerous lesions accompanied by an advanced stage of epithelial proliferation were found in two cases, in two other ones, in addition to the above mentioned lesions, breast cancer was discovered. The myoepithelial elements observed cytologically and histologically are important pathognomonic signs in theses patients. In spite of the few cases, the precancerous nature of gynecomastia, primarily in its proliferative forms, manifests itself.", "contents": "[(Gynecomastia as precancerous lesion: aspiration biopsy cytology and its histology)]. In 19 of 39 patients suffering from gynecomastia, between 1967 and 1979 aspiration biopsy cytology and surgery was performed by the author. Atypia and precancerous lesions accompanied by an advanced stage of epithelial proliferation were found in two cases, in two other ones, in addition to the above mentioned lesions, breast cancer was discovered. The myoepithelial elements observed cytologically and histologically are important pathognomonic signs in theses patients. In spite of the few cases, the precancerous nature of gynecomastia, primarily in its proliferative forms, manifests itself."}
{"id": "PMID:232746", "title": "[Effect of DNA supercoiling on transcription performed by normal and mutant Escherichia coli RNA-polymerases].", "content": "A specific DNA-gyrase, inhibitor, coumermycin A1, causes differential changes in the spectrum of proteins synthesized in E. coli wild types cells, while protein spectrum in the mutant cells with coumermycin-resistant DNA-gyrase is left unaffected. The mutation of RNA-polymerase RpoB265 lowers the sensitivity of bacteria to coumermycin A1, whereas the RpoC3 enhances it. The differences between the normal and mutant RpoB265 RNA polymerases on interaction in vitro with ColE1 DNA plasmid depend on its supercoiling. No dependences of this kind were detected when comparing the normal and RpoC3-RNA polymerase. The obtained data indicate that the template supercoiling may significantly affect the transcription in vivo and that the properties of RNA polymerase may in some cases define this influence.", "contents": "[Effect of DNA supercoiling on transcription performed by normal and mutant Escherichia coli RNA-polymerases]. A specific DNA-gyrase, inhibitor, coumermycin A1, causes differential changes in the spectrum of proteins synthesized in E. coli wild types cells, while protein spectrum in the mutant cells with coumermycin-resistant DNA-gyrase is left unaffected. The mutation of RNA-polymerase RpoB265 lowers the sensitivity of bacteria to coumermycin A1, whereas the RpoC3 enhances it. The differences between the normal and mutant RpoB265 RNA polymerases on interaction in vitro with ColE1 DNA plasmid depend on its supercoiling. No dependences of this kind were detected when comparing the normal and RpoC3-RNA polymerase. The obtained data indicate that the template supercoiling may significantly affect the transcription in vivo and that the properties of RNA polymerase may in some cases define this influence."}
{"id": "PMID:232745", "title": "[Analysis of vaccinia virus genome with restriction endonucleases EcoRI, BamHI, KpnI and HindIII].", "content": "Restriction endonucleases EcoRI, BamHI, Hind III and KpnI were used for analysis of acccinia virus DNA. The number and size of restriction endonuclease fragments were determined by gel electrophoresis and the analysis of 3H-labeled vaccinia virus DNA. It was shown that many EcoRI and BamHI fragments had the same and similar sizes. The exact number of EcoRI and BamHI fragments were estimated only after analysis of [3H]-labeled vaccinia DNA. The vaccinia genome sizes calculated from HindIII, KpnI and EcoRI are very close to the actual genome weight. But the sum of BamHI fragments is much lower than those determined by electron microscope method.", "contents": "[Analysis of vaccinia virus genome with restriction endonucleases EcoRI, BamHI, KpnI and HindIII]. Restriction endonucleases EcoRI, BamHI, Hind III and KpnI were used for analysis of acccinia virus DNA. The number and size of restriction endonuclease fragments were determined by gel electrophoresis and the analysis of 3H-labeled vaccinia virus DNA. It was shown that many EcoRI and BamHI fragments had the same and similar sizes. The exact number of EcoRI and BamHI fragments were estimated only after analysis of [3H]-labeled vaccinia DNA. The vaccinia genome sizes calculated from HindIII, KpnI and EcoRI are very close to the actual genome weight. But the sum of BamHI fragments is much lower than those determined by electron microscope method."}
{"id": "PMID:232747", "title": "[Isolation of DNA fraction bound to the axial structure of metaphase chromosomes and studies of renaturation].", "content": "Mitotic chromosomes of L cells (metaphase plates) were dehistonized by centrifugation through a layer of 2 M NaCl and then treated with restriction endonuclease EcoRI and HindIII. Alternatively, they were pretreated with EcoRI endonuclease. The DNA remaining attached to the axial structure of the chromosomes was isolated and investigated in renaturation experiments. It was found to be enriched in reiterated base sequences belonging to the satellite and to abundant intermediate repeats.", "contents": "[Isolation of DNA fraction bound to the axial structure of metaphase chromosomes and studies of renaturation]. Mitotic chromosomes of L cells (metaphase plates) were dehistonized by centrifugation through a layer of 2 M NaCl and then treated with restriction endonuclease EcoRI and HindIII. Alternatively, they were pretreated with EcoRI endonuclease. The DNA remaining attached to the axial structure of the chromosomes was isolated and investigated in renaturation experiments. It was found to be enriched in reiterated base sequences belonging to the satellite and to abundant intermediate repeats."}
{"id": "PMID:232749", "title": "Median neuropathy affecting the first dorsal interosseous muscle.", "content": "This case report documents the clinical entity of median nerve supply to the first dorsal interosseous muscle, which occurs in 3% of individuals. This must be remembered in evaluation of neuropathy involving the hand muscles.", "contents": "Median neuropathy affecting the first dorsal interosseous muscle. This case report documents the clinical entity of median nerve supply to the first dorsal interosseous muscle, which occurs in 3% of individuals. This must be remembered in evaluation of neuropathy involving the hand muscles."}
{"id": "PMID:232753", "title": "Cirrhosis of the liver: a reversible disease?", "content": "This paper is a speculative review of the irreversibility of cirrhosis of the liver. Experimental studies dealing with the specific issue of irreversibility of the process are summarized, and the following three general propositions are derived: 1. All experimental models of cirrhosis are reversible, provided the inciting agent is removed and sufficient time is allowed for the return to normal liver structure. 2. Experimental cirrhosis of the liver goes through two successive stages, differing (among many other features) in the time and completeness of their reversibility. 3. Increased reticulum fibers are more easily and completely resorbed than thick collagenous bundles. Human cases of cirrhosis of the liver in which the fact of regression appears to be sufficiently documented are also summarized. Most of them seem to fulfil the three conditions derived from the analysis of experimental data, namely, withdrawal of the etiologic agent at an early stage in their development (with a predominance of reticulum over collagen fibers) and allowance of sufficient time to document the disappearance of the disease. Experimental studies on the mechanisms of collagen degradation in general, and in the liver of mammals in particular, are also reviewed. It is concluded that much remains to be done but that the outcome is by no means hopeless.", "contents": "Cirrhosis of the liver: a reversible disease? This paper is a speculative review of the irreversibility of cirrhosis of the liver. Experimental studies dealing with the specific issue of irreversibility of the process are summarized, and the following three general propositions are derived: 1. All experimental models of cirrhosis are reversible, provided the inciting agent is removed and sufficient time is allowed for the return to normal liver structure. 2. Experimental cirrhosis of the liver goes through two successive stages, differing (among many other features) in the time and completeness of their reversibility. 3. Increased reticulum fibers are more easily and completely resorbed than thick collagenous bundles. Human cases of cirrhosis of the liver in which the fact of regression appears to be sufficiently documented are also summarized. Most of them seem to fulfil the three conditions derived from the analysis of experimental data, namely, withdrawal of the etiologic agent at an early stage in their development (with a predominance of reticulum over collagen fibers) and allowance of sufficient time to document the disappearance of the disease. Experimental studies on the mechanisms of collagen degradation in general, and in the liver of mammals in particular, are also reviewed. It is concluded that much remains to be done but that the outcome is by no means hopeless."}
{"id": "PMID:232748", "title": "Myosin changes in experimental 2,4-dichlorophenoxyacetate myopathy.", "content": "Young rats treated with 10 to 14 daily injections of 2,4-dichlorophenoxyacetate (2,4-D) developed a myopathy mainly involving fast muscles. Myosin isolated from the gastrocnemius muscles of treated and normal control animals differed in several respects. The Ca2+- and Mg2+-mediated ATPases were higher in myopathic muscle myosin than in normals. Alkylation of thiols by N-ethylmaleimide (NEM) induced an increase of Ca2+-activated ATPase that was higher in normal than in myopathic myosin. Trinitrophenylation of reactive amino groups by 2,4,6-trinitrobenzene sulfonate (TBS) induced on increase in Mg2+-mediated ATPase in both preparations, but the increase was higher in normals. Although the heavy- and light-chain pattern was identical in normal and myopathic myosin, during storage at 0 degrees C the relative amount of myopathic L2 light chain decreased. Myosins fragmented either by limited proteolysis with trypsin and chymotrypsin or by specific cleavage at tryptophanyl and cysteinyl peptide bonds showed differences on sodium dodecylsulfate (SDS)-polyacrylamide-gel electrophoresis. The results indicate that there is a change in the heavy chains of myosin isolated from the gastrocnemius muscle in 2,4-D-induced rat myopathy.", "contents": "Myosin changes in experimental 2,4-dichlorophenoxyacetate myopathy. Young rats treated with 10 to 14 daily injections of 2,4-dichlorophenoxyacetate (2,4-D) developed a myopathy mainly involving fast muscles. Myosin isolated from the gastrocnemius muscles of treated and normal control animals differed in several respects. The Ca2+- and Mg2+-mediated ATPases were higher in myopathic muscle myosin than in normals. Alkylation of thiols by N-ethylmaleimide (NEM) induced an increase of Ca2+-activated ATPase that was higher in normal than in myopathic myosin. Trinitrophenylation of reactive amino groups by 2,4,6-trinitrobenzene sulfonate (TBS) induced on increase in Mg2+-mediated ATPase in both preparations, but the increase was higher in normals. Although the heavy- and light-chain pattern was identical in normal and myopathic myosin, during storage at 0 degrees C the relative amount of myopathic L2 light chain decreased. Myosins fragmented either by limited proteolysis with trypsin and chymotrypsin or by specific cleavage at tryptophanyl and cysteinyl peptide bonds showed differences on sodium dodecylsulfate (SDS)-polyacrylamide-gel electrophoresis. The results indicate that there is a change in the heavy chains of myosin isolated from the gastrocnemius muscle in 2,4-D-induced rat myopathy."}
{"id": "PMID:232755", "title": "Latent infection by herpes simplex virus.", "content": "The experimental evidence contributing to the understanding of herpes simplex virus latent infection has been reviewed. The site of residence of the virus during silent periods of the disease appears to be, in the majority of instances, the sensory ganglion innervating the territory of prime infection. Little is known about the factors that bring about latent infection, maintain it, and regulate the production of infectious particles that cause recurrences.", "contents": "Latent infection by herpes simplex virus. The experimental evidence contributing to the understanding of herpes simplex virus latent infection has been reviewed. The site of residence of the virus during silent periods of the disease appears to be, in the majority of instances, the sensory ganglion innervating the territory of prime infection. Little is known about the factors that bring about latent infection, maintain it, and regulate the production of infectious particles that cause recurrences."}
{"id": "PMID:232756", "title": "An endonucleolytic activity of nuclease TT1 specific for superhelical DNA.", "content": "Highly purified nuclease TT1 from T. thermophilus HB8 acts on a linear single- and double-stranded DNA as an exonuclease and produces 5'-mononucleotides either from the 5'- or 3'-terminus. It was found that the enzyme also possesses an endonuclease activity specific for superhelical (form I) and single-stranded circular DNA. Form I of various kinds of DNA (phi X174, PM2, Co1E1 and RF 1010 etc.) is nicked to yield first relaxed circles (form II) and then nicked at the opposite site to yield unit length linear DNA (form III), which is subsequently hydrolyzed from the 5'- or 3'-terminus. A single cleavage of the form I of phi X174 DNA seemed to occur at a limited number of unique sites. Both endonuclease and the known exonuclease activities co-migrate on polyacrylmide gels, show the same pH and temperature optima, are stimulated by Mg2+ and are inactivated by EDTA similarly.", "contents": "An endonucleolytic activity of nuclease TT1 specific for superhelical DNA. Highly purified nuclease TT1 from T. thermophilus HB8 acts on a linear single- and double-stranded DNA as an exonuclease and produces 5'-mononucleotides either from the 5'- or 3'-terminus. It was found that the enzyme also possesses an endonuclease activity specific for superhelical (form I) and single-stranded circular DNA. Form I of various kinds of DNA (phi X174, PM2, Co1E1 and RF 1010 etc.) is nicked to yield first relaxed circles (form II) and then nicked at the opposite site to yield unit length linear DNA (form III), which is subsequently hydrolyzed from the 5'- or 3'-terminus. A single cleavage of the form I of phi X174 DNA seemed to occur at a limited number of unique sites. Both endonuclease and the known exonuclease activities co-migrate on polyacrylmide gels, show the same pH and temperature optima, are stimulated by Mg2+ and are inactivated by EDTA similarly."}
{"id": "PMID:232757", "title": "DNA glycosylases of human lymphoblastoid cells.", "content": "Lymphoblastoid cell lines were established after transformation by Epstein-Barr virus of peripheral lymphocytes from xeroderma pigmentosum (XP) patients and normal donors. These lines expressed B-lymphocyte characteristics. Typical characteristics related to XP of these cell lines were not altered by transformation. Extracts of these cells catalyzed release of uracil (Ura) and 3-methyladenine (3MeAde) from Ura-containing DNA (Ura-DNA) and methylated DNA (Me-DNA), respectively. These two activities, Ura-DNA glycosylase and 3MeAde-DNA glycosylase, differed in heat stability. Extracts released Ura more rapidly and 3MeAde more slowly from a single-stranded DNA than from a double-stranded DNA. On incubation with reconstituted chromatins prepared from Ura-DNA and Me-DNA, respectively, with calf thymus chromosomal protein, cell extracts released all the Ura but about half the 3MeAde residues. The activity levels of these two enzymes of XP cells were similar to those of normal cells.", "contents": "DNA glycosylases of human lymphoblastoid cells. Lymphoblastoid cell lines were established after transformation by Epstein-Barr virus of peripheral lymphocytes from xeroderma pigmentosum (XP) patients and normal donors. These lines expressed B-lymphocyte characteristics. Typical characteristics related to XP of these cell lines were not altered by transformation. Extracts of these cells catalyzed release of uracil (Ura) and 3-methyladenine (3MeAde) from Ura-containing DNA (Ura-DNA) and methylated DNA (Me-DNA), respectively. These two activities, Ura-DNA glycosylase and 3MeAde-DNA glycosylase, differed in heat stability. Extracts released Ura more rapidly and 3MeAde more slowly from a single-stranded DNA than from a double-stranded DNA. On incubation with reconstituted chromatins prepared from Ura-DNA and Me-DNA, respectively, with calf thymus chromosomal protein, cell extracts released all the Ura but about half the 3MeAde residues. The activity levels of these two enzymes of XP cells were similar to those of normal cells."}
{"id": "PMID:232758", "title": "The specific, diverse effects of purine and pyrimidine nucleoside-5'-di(tri)-3'-diphosphates on the eucaryote translation system in vitro.", "content": "All the eight 5'-di(tri)-3'-diphosphates of four common ribonucleosides were prepared by the enzymic pyrophosphoryl transfer catalysed by Streptomyces adephospholyticus ATP:nucleotide pyrophosphokinase (E.C.2.7.6.4) form dATP to the respective 5'-phosphates, and their effects on the translation of mRNAs by a wheat germ system in vitro were studied. (p) ppPupp decreased the total 14C-leucine incorporation directed by a rat liver mRNA whereas (p) ppPypp did not. With a silkworm pupa ovary mRNA, distinctly reverase results were obtained. Gel electrophoretic profiles of the translation products disclosed the mRNA species-specific stimulatory or inhibitory effects for each of the polyphosphates tested.", "contents": "The specific, diverse effects of purine and pyrimidine nucleoside-5'-di(tri)-3'-diphosphates on the eucaryote translation system in vitro. All the eight 5'-di(tri)-3'-diphosphates of four common ribonucleosides were prepared by the enzymic pyrophosphoryl transfer catalysed by Streptomyces adephospholyticus ATP:nucleotide pyrophosphokinase (E.C.2.7.6.4) form dATP to the respective 5'-phosphates, and their effects on the translation of mRNAs by a wheat germ system in vitro were studied. (p) ppPupp decreased the total 14C-leucine incorporation directed by a rat liver mRNA whereas (p) ppPypp did not. With a silkworm pupa ovary mRNA, distinctly reverase results were obtained. Gel electrophoretic profiles of the translation products disclosed the mRNA species-specific stimulatory or inhibitory effects for each of the polyphosphates tested."}
{"id": "PMID:232759", "title": "The primary sequence of the late region of polyoma virus DNA II. The expression of the late genes and comparison with DNA sequences of SV40 and BKV.", "content": "The nucleotide sequence of the late region of the polyoma virus genome has been deduced, which codes for the major capsid protein VP1 and the C-terminal region of the minor proteins VP2 and VP3. The amino acid sequence of VP1 predicted from the nucleotide sequence is in good agreement with the partial N-terminal sequence 1 and amino acid composition of VP1 2,3. When both nucleotide and amono acid sequences are compared with their counterparts in the related viruses, SV40 4,5 and BKV (R. Young, personal communication), extensive homologies are found along the entire regions of the viral genes. Maximum homologies appear to occur in the regions which code for the C-terminal of VP1, on the contrary of the result of heteroduplex analysis 6 with 6 with SV40 and polyoma virus DNAs.", "contents": "The primary sequence of the late region of polyoma virus DNA II. The expression of the late genes and comparison with DNA sequences of SV40 and BKV. The nucleotide sequence of the late region of the polyoma virus genome has been deduced, which codes for the major capsid protein VP1 and the C-terminal region of the minor proteins VP2 and VP3. The amino acid sequence of VP1 predicted from the nucleotide sequence is in good agreement with the partial N-terminal sequence 1 and amino acid composition of VP1 2,3. When both nucleotide and amono acid sequences are compared with their counterparts in the related viruses, SV40 4,5 and BKV (R. Young, personal communication), extensive homologies are found along the entire regions of the viral genes. Maximum homologies appear to occur in the regions which code for the C-terminal of VP1, on the contrary of the result of heteroduplex analysis 6 with 6 with SV40 and polyoma virus DNAs."}
{"id": "PMID:232760", "title": "Photobinding of 8-methoxypsoralen and changes in nuclease digestability of replicating SV40 chromatin.", "content": "To analyze the structure of the replicating regions of simian virus 40 nucleoprotein complex (SV40 chromatin), photochemical binding of 8-methoxypsoralen (8-MOP) and changes in digestability with micrococcal nuclease were studied. 8-MOP bound preferentially to the linker DNA of nucleosomes and strongly inhibited nuclease digestion. Nuclease digestability of newly synthesized DNA in the replicating chromatin was markedly increased, but it was inhibited in the early time of nuclease reaction by photobinding of 8-MOP. The data suggest that the replicating regions of chromatin are more exposed than the bulk of mature chromatin.", "contents": "Photobinding of 8-methoxypsoralen and changes in nuclease digestability of replicating SV40 chromatin. To analyze the structure of the replicating regions of simian virus 40 nucleoprotein complex (SV40 chromatin), photochemical binding of 8-methoxypsoralen (8-MOP) and changes in digestability with micrococcal nuclease were studied. 8-MOP bound preferentially to the linker DNA of nucleosomes and strongly inhibited nuclease digestion. Nuclease digestability of newly synthesized DNA in the replicating chromatin was markedly increased, but it was inhibited in the early time of nuclease reaction by photobinding of 8-MOP. The data suggest that the replicating regions of chromatin are more exposed than the bulk of mature chromatin."}
{"id": "PMID:232762", "title": "Uterine prostaglandin levels following stimulation of the decidual cell reaction: effects of indomethacin and tranylcypromine.", "content": "Prostaglandin E (PGE) and F (PGF) levels were measured in mouse uteri at various times after either trauma (hemostat crusing) or oil stimulation of the decidual cell reaction (DCR). The oil induced DCR led to an early increase (within 5 min) in both PGE and PGF levels. Both returned to baseline by 1 h after stimulation. A second peak in PGF levels was observed at 120 min after oil stimulation. This study demonstrates a distinct difference between the pattern of PGE and PGF changes in the uterus following oil stimulation of the DCR. Indomethacin pretreatment completely blocked the oil stimulated DCR as well as all prostaglandin increases following either stimulus. The trauma stimulated DCR was not completely blocked by indomethacin pretreatment. Pretreatment with tranylcypromine, an inhibitor of prostacyclin biosynthesis, did not block the prostaglandin E and F increases, but did block the oil stimulated DCR. These findings suggest that prostacyclin may be an early mediator of the DCR.", "contents": "Uterine prostaglandin levels following stimulation of the decidual cell reaction: effects of indomethacin and tranylcypromine. Prostaglandin E (PGE) and F (PGF) levels were measured in mouse uteri at various times after either trauma (hemostat crusing) or oil stimulation of the decidual cell reaction (DCR). The oil induced DCR led to an early increase (within 5 min) in both PGE and PGF levels. Both returned to baseline by 1 h after stimulation. A second peak in PGF levels was observed at 120 min after oil stimulation. This study demonstrates a distinct difference between the pattern of PGE and PGF changes in the uterus following oil stimulation of the DCR. Indomethacin pretreatment completely blocked the oil stimulated DCR as well as all prostaglandin increases following either stimulus. The trauma stimulated DCR was not completely blocked by indomethacin pretreatment. Pretreatment with tranylcypromine, an inhibitor of prostacyclin biosynthesis, did not block the prostaglandin E and F increases, but did block the oil stimulated DCR. These findings suggest that prostacyclin may be an early mediator of the DCR."}
{"id": "PMID:232763", "title": "Effect of modulators of cytoskeletal function on desensitization and recovery of PGE2-responsive ovarian adenylate cyclase.", "content": "Exposure of cultured Graafian follicles to PGE2 for 20 h resulted in a loss of the cyclic AMP response to fresh hormone. This desensitization was prevented by addition to the medium of D2O (25--50%) or Li+ (0.6--6 mM), agents believed to stabilize microtubules, as well as by phalloidin (1.0--10 microM), believed to stabilize the polymerized state of actin, in a dose-dependent manner. The spontaneous recovery of responsiveness to PGE2 upon incubation of refractory follicles for 6 h in hormone-free medium was prevented by addition to the medium of cytochalasin B (CB; 3 microgram/ml) or of the actin-binding myosin subfragment HMM S-1 (80 microgram/ml) or of anti-actin serum; viz. by agents likely to interfere with microfilament function. D2O (50%) caused morphological damage to the inner layer of the membrana granulosa and severe depression of protein synthesis. The other drugs used (phalloidin, LiCl and cytochalasin B) had no such effects. Resensitization of refractory follicles was also prevented by cycloheximide (10 micrograms/ml) and by actinomycin D (10 micrograms/ml). It is speculated that the recovery process may involve the insertion of a newly synthesized protein, such as PG-receptor, into the membrane by a mechanism dependent on microfilament action. These findings provide suggestive evidence for the hypothesis that cytoskeletal elements associated with the cell membrane take part in the modulation of the adenylate cyclase response to hormones.", "contents": "Effect of modulators of cytoskeletal function on desensitization and recovery of PGE2-responsive ovarian adenylate cyclase. Exposure of cultured Graafian follicles to PGE2 for 20 h resulted in a loss of the cyclic AMP response to fresh hormone. This desensitization was prevented by addition to the medium of D2O (25--50%) or Li+ (0.6--6 mM), agents believed to stabilize microtubules, as well as by phalloidin (1.0--10 microM), believed to stabilize the polymerized state of actin, in a dose-dependent manner. The spontaneous recovery of responsiveness to PGE2 upon incubation of refractory follicles for 6 h in hormone-free medium was prevented by addition to the medium of cytochalasin B (CB; 3 microgram/ml) or of the actin-binding myosin subfragment HMM S-1 (80 microgram/ml) or of anti-actin serum; viz. by agents likely to interfere with microfilament function. D2O (50%) caused morphological damage to the inner layer of the membrana granulosa and severe depression of protein synthesis. The other drugs used (phalloidin, LiCl and cytochalasin B) had no such effects. Resensitization of refractory follicles was also prevented by cycloheximide (10 micrograms/ml) and by actinomycin D (10 micrograms/ml). It is speculated that the recovery process may involve the insertion of a newly synthesized protein, such as PG-receptor, into the membrane by a mechanism dependent on microfilament action. These findings provide suggestive evidence for the hypothesis that cytoskeletal elements associated with the cell membrane take part in the modulation of the adenylate cyclase response to hormones."}
{"id": "PMID:232764", "title": "Prostacyclin stimulation of dog arterial cyclic AMP levels.", "content": "Prostacyclin (PGI2) dose-dependently increases the adenosine 3',5'-cyclic monophosphate (cyclic AMP) levels in canine femoral, carotid, and canine and bovine coronary arteries. The prostacyclin-stimulation is enhanced by phosphodiesterase inhibitors, and is readily measurable after 60 sec incubation. The prostaglandin endoperoxide PGH2, but not PGH1, also elevates cAMP levels in femoral arteries. Inhibition of arterial prostacyclin synthetase with 28 microM 9,11-azoprosta-5,13-dienoic acid (azo analog I) blocks the PGH2-stimulation of cAMP accumulation. Azo analog I does not attenuate a direct PGI2 stimulation, indicating that the PGH2 dependent elevation of cAMP is due to conversion of PGH2 to PGI2 by the artery. PGI2 and PGE1 increase cyclic AMP levels and relax dog femoral and bovine coronary arteries, while PGE2, which actually contracts bovine coronary arteries, has no effect on arterial cyclic AMP levels. The significance of the PGI2-stimulation of arterial cyclic AMP is not known, but it is probably related to relaxation of arterial strips.", "contents": "Prostacyclin stimulation of dog arterial cyclic AMP levels. Prostacyclin (PGI2) dose-dependently increases the adenosine 3',5'-cyclic monophosphate (cyclic AMP) levels in canine femoral, carotid, and canine and bovine coronary arteries. The prostacyclin-stimulation is enhanced by phosphodiesterase inhibitors, and is readily measurable after 60 sec incubation. The prostaglandin endoperoxide PGH2, but not PGH1, also elevates cAMP levels in femoral arteries. Inhibition of arterial prostacyclin synthetase with 28 microM 9,11-azoprosta-5,13-dienoic acid (azo analog I) blocks the PGH2-stimulation of cAMP accumulation. Azo analog I does not attenuate a direct PGI2 stimulation, indicating that the PGH2 dependent elevation of cAMP is due to conversion of PGH2 to PGI2 by the artery. PGI2 and PGE1 increase cyclic AMP levels and relax dog femoral and bovine coronary arteries, while PGE2, which actually contracts bovine coronary arteries, has no effect on arterial cyclic AMP levels. The significance of the PGI2-stimulation of arterial cyclic AMP is not known, but it is probably related to relaxation of arterial strips."}
{"id": "PMID:232765", "title": "The determination of bone age in the elbow as compared to the hand. A study in 390 children.", "content": "In a prospective study, bone age (BA) from both hand and elbow was assessed in 390 children, aged 6-15 years, in order to determine: (a) whether or not BA assessment from the hand and from the elbow give comparable results, and (b) whether the accuracy of predicting skeletal age from the hand may be improved by the additional BA determination in the elbow. BA assessment in the hand was performed according to the method of Greulich and Pyle while the standards of Schinz and Baensch were used for the elbow. Statistical analysis of data was carried out according to age groups as well as according to groups of clinical diagnoses. With only one exception in the group of so-called \"healthy individuals\", there was no difference between \"hand age\" and \"elbow age\". Thus, except in a very small group of subjects, both methods of BA assessment were found to be equivalent in predicting skeletal age in children between 6-15 years. Equivocal results were obtained regarding the question of whether the accuracy of BA assessment in the hand may be improved by the simultaneous BA determination from the elbow. Until further studies on larger statistical material provide more conclusive information in this matter, we feel that the combined determination of BA in the hand and elbow is not warranted for clinical purposes.", "contents": "The determination of bone age in the elbow as compared to the hand. A study in 390 children. In a prospective study, bone age (BA) from both hand and elbow was assessed in 390 children, aged 6-15 years, in order to determine: (a) whether or not BA assessment from the hand and from the elbow give comparable results, and (b) whether the accuracy of predicting skeletal age from the hand may be improved by the additional BA determination in the elbow. BA assessment in the hand was performed according to the method of Greulich and Pyle while the standards of Schinz and Baensch were used for the elbow. Statistical analysis of data was carried out according to age groups as well as according to groups of clinical diagnoses. With only one exception in the group of so-called \"healthy individuals\", there was no difference between \"hand age\" and \"elbow age\". Thus, except in a very small group of subjects, both methods of BA assessment were found to be equivalent in predicting skeletal age in children between 6-15 years. Equivocal results were obtained regarding the question of whether the accuracy of BA assessment in the hand may be improved by the simultaneous BA determination from the elbow. Until further studies on larger statistical material provide more conclusive information in this matter, we feel that the combined determination of BA in the hand and elbow is not warranted for clinical purposes."}
{"id": "PMID:232761", "title": "The effect of baclofen on the hind limb flexor reflex of the spinal rat.", "content": "The effect of baclofen on the hind limb flexor reflex of the spinal rat was studied. Baclofen inhibited the flexor reflex, this effect not being antagonized by picrotoxin and bicuculline. Baclofen reduced the stimulating action of quipazine and LSD, had no effect on the clonidine-induced reflex stimulation, but inhibited the flexor reflex stimulation induced by amphetamine and fenfluramine. The results obtained bring forth some doubts as to the GABA-mimetic action of baclofen. The action of baclofen on the spinal cord seems to be directed mainly to the presynaptic part of the noradrenergic and serotonergic systems.", "contents": "The effect of baclofen on the hind limb flexor reflex of the spinal rat. The effect of baclofen on the hind limb flexor reflex of the spinal rat was studied. Baclofen inhibited the flexor reflex, this effect not being antagonized by picrotoxin and bicuculline. Baclofen reduced the stimulating action of quipazine and LSD, had no effect on the clonidine-induced reflex stimulation, but inhibited the flexor reflex stimulation induced by amphetamine and fenfluramine. The results obtained bring forth some doubts as to the GABA-mimetic action of baclofen. The action of baclofen on the spinal cord seems to be directed mainly to the presynaptic part of the noradrenergic and serotonergic systems."}
{"id": "PMID:232766", "title": "[Breast cancer in men].", "content": "Carcinoma of the breast is relatively uncommon in men. Represents somewhere between 0.9 to 1.5 of all tumors of the breast. Most patients are within the 7th to 8th decade of life. The most common symptoms at the time of presentation are a tumor mass in either breast, ulceration of the nipple or nipple retraction or fixation of the skin. Extension to the axiliar nodes takes place early in the course of the disease. The presence of nipple discharge should be considered expression of carcinoma of the breast unless otherwise proven. The final diagnosis is established by biopsy. The most common form of carcinoma of the breast is the ductal carcinoma. The surgical management takes basically that followed in carcinoma of the breast in the female patient. Also orquiectomy has been used which is equivalent to ovariectomy in woman. In the presence of metastasis both estrogens and androgens have been used. Hypophysectomy and post-op radiation therapy has been used. Most recently chemotherapy has been widely used in those cases with widespread metastasis. However, in spite of all these efforts carcinoma of the breast in the male still carries a very serious prognosis. We present our experience in 16 cases.", "contents": "[Breast cancer in men]. Carcinoma of the breast is relatively uncommon in men. Represents somewhere between 0.9 to 1.5 of all tumors of the breast. Most patients are within the 7th to 8th decade of life. The most common symptoms at the time of presentation are a tumor mass in either breast, ulceration of the nipple or nipple retraction or fixation of the skin. Extension to the axiliar nodes takes place early in the course of the disease. The presence of nipple discharge should be considered expression of carcinoma of the breast unless otherwise proven. The final diagnosis is established by biopsy. The most common form of carcinoma of the breast is the ductal carcinoma. The surgical management takes basically that followed in carcinoma of the breast in the female patient. Also orquiectomy has been used which is equivalent to ovariectomy in woman. In the presence of metastasis both estrogens and androgens have been used. Hypophysectomy and post-op radiation therapy has been used. Most recently chemotherapy has been widely used in those cases with widespread metastasis. However, in spite of all these efforts carcinoma of the breast in the male still carries a very serious prognosis. We present our experience in 16 cases."}
{"id": "PMID:232767", "title": "[Cancer of the alpha cells of the pancreas].", "content": "Endocrine tumors of the pancreas are rare. One of them is the so called alpha cell carcinoma also called glucagonoma usually associated with diabetes and skin lesions somewhat typical. A case of a male patient fifty-three years of age with clinical diabetes mellitus and generalized dermatitis is presented. The pancreatic scan showed some enlargement of the head of the pancreas as well as the body which was confirmed by ultrasound. Angiography showed that this change was due to pancreatic tumor with intrahepatic metastasis. The patient was taken to surgery where a glucagonoma of the pancreas was found. This case is reported because only 32 other cases have been reported in the literature.", "contents": "[Cancer of the alpha cells of the pancreas]. Endocrine tumors of the pancreas are rare. One of them is the so called alpha cell carcinoma also called glucagonoma usually associated with diabetes and skin lesions somewhat typical. A case of a male patient fifty-three years of age with clinical diabetes mellitus and generalized dermatitis is presented. The pancreatic scan showed some enlargement of the head of the pancreas as well as the body which was confirmed by ultrasound. Angiography showed that this change was due to pancreatic tumor with intrahepatic metastasis. The patient was taken to surgery where a glucagonoma of the pancreas was found. This case is reported because only 32 other cases have been reported in the literature."}
{"id": "PMID:232768", "title": "[Longitudinal study of 5 patients with \"primary empty sella\" (author's transl)].", "content": "The clinical symptoms and the radiographic findings of five female patients with \"primary empty sella\" were studied. The patients were treated with corticosteroid therapy and the clinical syndrome, with the exception of optic subatrophy of the left eye in one patient and of both eyes in another patients, improved in all of them. In subsequent controls, the radiographic findings did not show any evolution suggesting that the cause of the empty sella syndrome is a potentially regressive element (endocranial hypertension?). The small number of our cases does not prove with any certainty that corticosteroid treatment, was beneficial but as improvement occurred and in all the subjects this therapy should be tried in other patients with \"empty sella\" syndrome. The possible improvement of the empty sella syndrome has to be taken into account before deciding on surgical intervention.", "contents": "[Longitudinal study of 5 patients with \"primary empty sella\" (author's transl)]. The clinical symptoms and the radiographic findings of five female patients with \"primary empty sella\" were studied. The patients were treated with corticosteroid therapy and the clinical syndrome, with the exception of optic subatrophy of the left eye in one patient and of both eyes in another patients, improved in all of them. In subsequent controls, the radiographic findings did not show any evolution suggesting that the cause of the empty sella syndrome is a potentially regressive element (endocranial hypertension?). The small number of our cases does not prove with any certainty that corticosteroid treatment, was beneficial but as improvement occurred and in all the subjects this therapy should be tried in other patients with \"empty sella\" syndrome. The possible improvement of the empty sella syndrome has to be taken into account before deciding on surgical intervention."}
{"id": "PMID:232772", "title": "[Red cell indices in the aged. 1 726 patients over the age of 70 (author's transl)].", "content": "Statistical analysis of red cell constants in 1 726 patients over the age of 70 shows that red cell counts, hemoglobin and hematocrits are slightly lower than those in young adults. However, the quality of the red cells is normal, because the MCV (mean cell volume) and MCHC (mean cell hemoglobin concentration) are normal.", "contents": "[Red cell indices in the aged. 1 726 patients over the age of 70 (author's transl)]. Statistical analysis of red cell constants in 1 726 patients over the age of 70 shows that red cell counts, hemoglobin and hematocrits are slightly lower than those in young adults. However, the quality of the red cells is normal, because the MCV (mean cell volume) and MCHC (mean cell hemoglobin concentration) are normal."}
{"id": "PMID:232773", "title": "[Frequency and etiology of anemia in patients over the age of 70 (author's transl)].", "content": "The study of 1 726 patients living in homes for the aged, or hospitalized shows that 20% of them have anemia. There is no increase in prevalence of the disease in females. A wide variety of mechanisms may cause anemia. However, chronic bleeding of essentially digestive origin is the most common. Several anemia-causing factors are particularly frequent in the aged: bleeding, inflammation, nutritional deficiencies, bone marrow failure. Diagnosis is complicated and may require examinations which are not always easily accepted by the aged.", "contents": "[Frequency and etiology of anemia in patients over the age of 70 (author's transl)]. The study of 1 726 patients living in homes for the aged, or hospitalized shows that 20% of them have anemia. There is no increase in prevalence of the disease in females. A wide variety of mechanisms may cause anemia. However, chronic bleeding of essentially digestive origin is the most common. Several anemia-causing factors are particularly frequent in the aged: bleeding, inflammation, nutritional deficiencies, bone marrow failure. Diagnosis is complicated and may require examinations which are not always easily accepted by the aged."}
{"id": "PMID:232775", "title": "[\"Non-secreting\" plasma cell myeloma preceded by refractory sideroblastic anemia (author's transl)].", "content": "The authors report the association of a refractory sideroblastic anemia and a \"non-excreting\" plasma cell myeloma. The anemia was observed 8 years before the onset of the myeloma, which had typical hematological characteristics. Both kappa and gamma light chains were found in the cytoplasm and on the surface of the plasma cells. Pathologic characteristics of this type of myeloma are briefly recalled, as well as the relationships between sideroblastic anemia and kahler's disease, an example of disorders of two lines of hematopoiesis (erythrocytes and leucocytes).", "contents": "[\"Non-secreting\" plasma cell myeloma preceded by refractory sideroblastic anemia (author's transl)]. The authors report the association of a refractory sideroblastic anemia and a \"non-excreting\" plasma cell myeloma. The anemia was observed 8 years before the onset of the myeloma, which had typical hematological characteristics. Both kappa and gamma light chains were found in the cytoplasm and on the surface of the plasma cells. Pathologic characteristics of this type of myeloma are briefly recalled, as well as the relationships between sideroblastic anemia and kahler's disease, an example of disorders of two lines of hematopoiesis (erythrocytes and leucocytes)."}
{"id": "PMID:232774", "title": "[Crohn's disease (acute regional colitis) (author's transl)].", "content": "This article reports the observation of acute form of Crohn's disease, limited to colonic involvement, in a 40-year old female. Diagnosis was based upon pathologic examination of biopsy. The patient died after four months of acute disease. Clinical and paraclinical justification of the diagnosis of Crohn's disease (colonic), as well as description of treatment are given.", "contents": "[Crohn's disease (acute regional colitis) (author's transl)]. This article reports the observation of acute form of Crohn's disease, limited to colonic involvement, in a 40-year old female. Diagnosis was based upon pathologic examination of biopsy. The patient died after four months of acute disease. Clinical and paraclinical justification of the diagnosis of Crohn's disease (colonic), as well as description of treatment are given."}
{"id": "PMID:232776", "title": "[Primary hydatic cyst of the lung. Diagnostic problems (author's transl)].", "content": "Diagnosis of primary cystic disease of the lung is often difficult, and because of this, in non-endemic regions, patients are often referred to the surgeon with an erroneous diagnosis. Clinical signs are completely non-specific. The most common one is hemoptysis; X-rays often fail to confirm hydatic cyst because of the volume, topography, or rupture of the cyst. Biological tests are often of little help. Serological reactions are negative in over one-half of the cases. The advantage of other complementary examinations (bronchiography, bronchoscopy, angiography, echotomography, scintigraphy) including transparietal punctions of the cyst, are discussed in light of the literature.", "contents": "[Primary hydatic cyst of the lung. Diagnostic problems (author's transl)]. Diagnosis of primary cystic disease of the lung is often difficult, and because of this, in non-endemic regions, patients are often referred to the surgeon with an erroneous diagnosis. Clinical signs are completely non-specific. The most common one is hemoptysis; X-rays often fail to confirm hydatic cyst because of the volume, topography, or rupture of the cyst. Biological tests are often of little help. Serological reactions are negative in over one-half of the cases. The advantage of other complementary examinations (bronchiography, bronchoscopy, angiography, echotomography, scintigraphy) including transparietal punctions of the cyst, are discussed in light of the literature."}
{"id": "PMID:232777", "title": "[Lactic acidosis and intensive care. 16 cases (author's transl)].", "content": "Sixteen cases of lactic acidosis are reported: 7 phenformin treated diabetes, 5 cardiovascular diseases (2 myocardial infractions, 2 pulmonary embolisms, 1 heart failure). In 2 patients no etiology was found. Concomittant renal failure or liver diseases were found in respectively 9 and 4 cases. Patients presented the usual criteria of lactic acidosis: clinical, polypnea, severe hypotension (9/16), peripheral symptoms of shock (12/16), hypothermia (9/16), abdominal pain (9/16): biologically, acidosis (pH = 6,99 +/- 0,01, HCO3- = 5,9 +/- 1,5 mmol), hyperlactatemia (14,1 +/- 3,6 mmol/l) with hig lactate/pyruvate ratio (105 +/- 73), and anion gap (24,3 +/- 4,2 mmol/l). Sodium bicarbonate infusion was performed in all cases (2,5 to 42 mmol/kg). Few cases required volhemic expansion or furosemid induced diuresis. One patient was treated with extrarenal dialysis. 13 patients were alkalinised with less than 185% of estimated deficit measured from alkalin reserve: 12 died. 3 patients received 185% more than this deficit, associated with furosemid (1,8 to 12,5 mg/kg): only one patient died ten days after by casual disease, with lactatemia of 3,2 mmol/l. In spite of the small number of patients, these findings suggest that an early and massive alkalinisation, with large doses of furosemid, can improve the severe lactic acidosis prognosis.", "contents": "[Lactic acidosis and intensive care. 16 cases (author's transl)]. Sixteen cases of lactic acidosis are reported: 7 phenformin treated diabetes, 5 cardiovascular diseases (2 myocardial infractions, 2 pulmonary embolisms, 1 heart failure). In 2 patients no etiology was found. Concomittant renal failure or liver diseases were found in respectively 9 and 4 cases. Patients presented the usual criteria of lactic acidosis: clinical, polypnea, severe hypotension (9/16), peripheral symptoms of shock (12/16), hypothermia (9/16), abdominal pain (9/16): biologically, acidosis (pH = 6,99 +/- 0,01, HCO3- = 5,9 +/- 1,5 mmol), hyperlactatemia (14,1 +/- 3,6 mmol/l) with hig lactate/pyruvate ratio (105 +/- 73), and anion gap (24,3 +/- 4,2 mmol/l). Sodium bicarbonate infusion was performed in all cases (2,5 to 42 mmol/kg). Few cases required volhemic expansion or furosemid induced diuresis. One patient was treated with extrarenal dialysis. 13 patients were alkalinised with less than 185% of estimated deficit measured from alkalin reserve: 12 died. 3 patients received 185% more than this deficit, associated with furosemid (1,8 to 12,5 mg/kg): only one patient died ten days after by casual disease, with lactatemia of 3,2 mmol/l. In spite of the small number of patients, these findings suggest that an early and massive alkalinisation, with large doses of furosemid, can improve the severe lactic acidosis prognosis."}
{"id": "PMID:232779", "title": "[Plasma androgens in boys from birth to adolescence (author's transl)].", "content": "Plasma testosterone, androstenedione, dehydroepiandrosterone and dehydroepiandrosterone-sulfate were measured by radioimmunoassay in 222 normal boys aged 1 hour to 18 years and 40 normal men aged 20 to 40 years. Three periods of high testosterone levels were observed in boys during extra-uterine life: first day (mean level 12 nmol/l), from the 12th to the 119th day (9 nmol/l) and from 13 years onwards in pubertal boys; the highest values were  reached between 20 and 40 years (18 nmol/l). Androstenedione curve exhibited three coincident high concentrations phases: mean level at birth 8.7 nmol/l, and from 12th to 119th day 2.6 nmol/l. The lowest values were observed between 2 and 4 years; then a progressive increase occured up to adult age levels: 3.5 nmol/l. Dehydroepiandrosterone mean level was high at birth (20 nmol/l) then decreased slowly, either regularly or with a rebound during the 2nd month, a minimum being reached between 2 and 4 years (0.28 nmol/l). It increased thereafter exponentially up to adult levels reached after the age of 16 years (14 nmol/l). Dehydroepiandrosterone-sulfate mean level decreased regularly from birth to the second year, then its curve paralleled the dehydroepiandrosterone curve.", "contents": "[Plasma androgens in boys from birth to adolescence (author's transl)]. Plasma testosterone, androstenedione, dehydroepiandrosterone and dehydroepiandrosterone-sulfate were measured by radioimmunoassay in 222 normal boys aged 1 hour to 18 years and 40 normal men aged 20 to 40 years. Three periods of high testosterone levels were observed in boys during extra-uterine life: first day (mean level 12 nmol/l), from the 12th to the 119th day (9 nmol/l) and from 13 years onwards in pubertal boys; the highest values were  reached between 20 and 40 years (18 nmol/l). Androstenedione curve exhibited three coincident high concentrations phases: mean level at birth 8.7 nmol/l, and from 12th to 119th day 2.6 nmol/l. The lowest values were observed between 2 and 4 years; then a progressive increase occured up to adult age levels: 3.5 nmol/l. Dehydroepiandrosterone mean level was high at birth (20 nmol/l) then decreased slowly, either regularly or with a rebound during the 2nd month, a minimum being reached between 2 and 4 years (0.28 nmol/l). It increased thereafter exponentially up to adult levels reached after the age of 16 years (14 nmol/l). Dehydroepiandrosterone-sulfate mean level decreased regularly from birth to the second year, then its curve paralleled the dehydroepiandrosterone curve."}
{"id": "PMID:232780", "title": "[Treatment of hypertension with Sotalol (author's transl)].", "content": "Sotalol is a new beta-adrenoceptor blocking drug without membrane stabilizing activity, without intrinsic sympathomimetic activity and with a low cardio-depressive effect. This beta-blocking agent has an half-life much longer than the other beta-blockers (T 1/2 from 10 to 13 hours). The antihypertensive effect and tolerance of 160 mg tablets of sotalol were studied in 35 hypertensive patients aged 18 to 60 years. The drug was administred once daily in the morning. Sotalol prescribed as the only antihypertensive drug lowered the blood pressure to normal values in 21 cases with a single daily of 1 to 3 tablets. In 8 patients a partial response was obtained (25 % reduction of the initial systolic and diatolic pressure). Six patients did not respond. The clinical and biological tolerances were good; Sotalol was only discontinued in three cases. Sotalol appears to be an effective and well tolerated antihypertensive agent, specially for the treatment of moderate and recent essential hypertension in young patients.", "contents": "[Treatment of hypertension with Sotalol (author's transl)]. Sotalol is a new beta-adrenoceptor blocking drug without membrane stabilizing activity, without intrinsic sympathomimetic activity and with a low cardio-depressive effect. This beta-blocking agent has an half-life much longer than the other beta-blockers (T 1/2 from 10 to 13 hours). The antihypertensive effect and tolerance of 160 mg tablets of sotalol were studied in 35 hypertensive patients aged 18 to 60 years. The drug was administred once daily in the morning. Sotalol prescribed as the only antihypertensive drug lowered the blood pressure to normal values in 21 cases with a single daily of 1 to 3 tablets. In 8 patients a partial response was obtained (25 % reduction of the initial systolic and diatolic pressure). Six patients did not respond. The clinical and biological tolerances were good; Sotalol was only discontinued in three cases. Sotalol appears to be an effective and well tolerated antihypertensive agent, specially for the treatment of moderate and recent essential hypertension in young patients."}
{"id": "PMID:232781", "title": "[Histological and immunofluorescence study of forty two cases of D\u00fchring-Brocq disease (author's transl)].", "content": "Fourty-two cases of D\u00fchring-Brocq disease were analysed clinically, histologically and with direct and indirect immunofluorescence. One could only discriminate between bullous pemphigoid and dermatitis herpetiformis when all those criteriors were studied together. 17 cases were clinically composite ; histological and immunofluorescent analyses differentiated between 16 cases of bullous pemphigoid and 1 case of dermatitis herpetiformis.", "contents": "[Histological and immunofluorescence study of forty two cases of D\u00fchring-Brocq disease (author's transl)]. Fourty-two cases of D\u00fchring-Brocq disease were analysed clinically, histologically and with direct and indirect immunofluorescence. One could only discriminate between bullous pemphigoid and dermatitis herpetiformis when all those criteriors were studied together. 17 cases were clinically composite ; histological and immunofluorescent analyses differentiated between 16 cases of bullous pemphigoid and 1 case of dermatitis herpetiformis."}
{"id": "PMID:232783", "title": "[Acute pancreatitis and cholelithiasis. A study of thirty cases (author's transl)].", "content": "The authors report a series of 30 cases of acute pancreatitis associated with cholelithiasis. There were 9 cases of necrotizing pancreatitis and the latter group included the 4 deaths observed in this series. Clinical, radiological and laboratory data were in favor of this association in 24 out of the 30 cases. Cholelithiasis appeared to be directly responsible for initiating the pancreatitis in 1/3 of cases. In another 1/3 of cases the mecanism was thought to be related to scarring of the sphincter of Oddi. In the remaining 1/3 of cases no direct relationship could be found. On the basis of these findings, the authors recommend that emergency surgery be reserved for these cases in which cholelithiasis appears to be the etiology. (The biliary syndrome overshadowing the pancreatic syndrome) and to postpone treatment of pancreatic lesions. In all other cases, the authors suggest to keep elective surgery, for after a period of initial conservative treatment with the hope of then treating together biliary and pancreatic lesions.", "contents": "[Acute pancreatitis and cholelithiasis. A study of thirty cases (author's transl)]. The authors report a series of 30 cases of acute pancreatitis associated with cholelithiasis. There were 9 cases of necrotizing pancreatitis and the latter group included the 4 deaths observed in this series. Clinical, radiological and laboratory data were in favor of this association in 24 out of the 30 cases. Cholelithiasis appeared to be directly responsible for initiating the pancreatitis in 1/3 of cases. In another 1/3 of cases the mecanism was thought to be related to scarring of the sphincter of Oddi. In the remaining 1/3 of cases no direct relationship could be found. On the basis of these findings, the authors recommend that emergency surgery be reserved for these cases in which cholelithiasis appears to be the etiology. (The biliary syndrome overshadowing the pancreatic syndrome) and to postpone treatment of pancreatic lesions. In all other cases, the authors suggest to keep elective surgery, for after a period of initial conservative treatment with the hope of then treating together biliary and pancreatic lesions."}
{"id": "PMID:232788", "title": "Isolation and toxicological study of tetrahydrocannabivarol, an homolog of tetrahydrocannabinol (delta 1--THC).", "content": "Selection and culture in a Phytotron of plants of Cannabis sativa L. with high content of propyl-THC are obtained. Then it was possible to isolate a large quantity of propyl-THC by column chromatography. Spectroscopic analysis is done. Pharmacological tests are being run; first results revealed the allergenicity of this substance by comparison with the properties of tetrahydrocannabinol, the active principle of Cannabis.", "contents": "Isolation and toxicological study of tetrahydrocannabivarol, an homolog of tetrahydrocannabinol (delta 1--THC). Selection and culture in a Phytotron of plants of Cannabis sativa L. with high content of propyl-THC are obtained. Then it was possible to isolate a large quantity of propyl-THC by column chromatography. Spectroscopic analysis is done. Pharmacological tests are being run; first results revealed the allergenicity of this substance by comparison with the properties of tetrahydrocannabinol, the active principle of Cannabis."}
{"id": "PMID:232789", "title": "Electroretinographic study during acute Aramite intoxication of the white mouse.", "content": "Aramite was injected to white mice and the electroretinograms recorded in response to electronic flashes. The following phenomena were remarked: a more and more important flattening of a-waves; a simultaneous collapse of b-waves; a more and more delayed return of a-waves to the isoelectric line; vanishing c-waves. Those actions were explained by an intoxication of the photoreceptors by Aramite and by a resulting difficulty of the photoreceptors to stimulate bipolar cells.", "contents": "Electroretinographic study during acute Aramite intoxication of the white mouse. Aramite was injected to white mice and the electroretinograms recorded in response to electronic flashes. The following phenomena were remarked: a more and more important flattening of a-waves; a simultaneous collapse of b-waves; a more and more delayed return of a-waves to the isoelectric line; vanishing c-waves. Those actions were explained by an intoxication of the photoreceptors by Aramite and by a resulting difficulty of the photoreceptors to stimulate bipolar cells."}
{"id": "PMID:232784", "title": "[Acute thrombocytopenic purpura associated with fenoprofene (author's transl)].", "content": "A 73-year-old woman, taking daily 3 to 4 tablets (900 to 1200 mg) of fenoprofene for 2 weeks, had a purpura related to an acute peripheric thrombocytopenia (platelet count of 24 000/mm3) with fast regression when we have stopped therapy. It is the second case of literature. This drug is also capable of causing acute agranulocytosis.", "contents": "[Acute thrombocytopenic purpura associated with fenoprofene (author's transl)]. A 73-year-old woman, taking daily 3 to 4 tablets (900 to 1200 mg) of fenoprofene for 2 weeks, had a purpura related to an acute peripheric thrombocytopenia (platelet count of 24 000/mm3) with fast regression when we have stopped therapy. It is the second case of literature. This drug is also capable of causing acute agranulocytosis."}
{"id": "PMID:232782", "title": "[Stenosis of the left coronary artery: a report on 50 cases (author's transl)].", "content": "Stenosis of the left coronary artery differs from other atheromatous lesions by the severity of the affection. It is not a rare condition as it occured in 50 out of 750 patients. Clinical and electrocardiographic signs are not truly specific and coronarography is essential for diagnosis even though this procedure carries a certain risk of accidents (2%). At a time when medical and surgical treatment of coronary insufficiency is being compared, stenosis of the left coronary insufficiency is being compared, stenosis of the left coronary artery definitely required operative intervention which improves both functional prognosis and mortality.", "contents": "[Stenosis of the left coronary artery: a report on 50 cases (author's transl)]. Stenosis of the left coronary artery differs from other atheromatous lesions by the severity of the affection. It is not a rare condition as it occured in 50 out of 750 patients. Clinical and electrocardiographic signs are not truly specific and coronarography is essential for diagnosis even though this procedure carries a certain risk of accidents (2%). At a time when medical and surgical treatment of coronary insufficiency is being compared, stenosis of the left coronary insufficiency is being compared, stenosis of the left coronary artery definitely required operative intervention which improves both functional prognosis and mortality."}
{"id": "PMID:232790", "title": "[Biological age in children with clefts].", "content": "The skeletal and the dental maturity in a group of 189 children with cleft lip and/or cleft palate were determined by means of X-rays of the wrist joint and orthopantomogrammes. In 60 children, anthropometric determinations were also performed. 486 normal children involved in the Nijmegen growth study served as control subjects. The ages ranged from 4 to 14 years. A retardation in dental development was evidenced in boys with clefts. There was no remarkable difference in dental development between girls with clefts and girls without clefts. The progression in skeletal maturity was greater in girls with clefts than in girls without clefts. There was no remarkable difference in skeletal maturity between boys with clefts and normal boys. The determination of 10 anthropometric values revealed only a few remarkable differences between children with clefts and normal children.", "contents": "[Biological age in children with clefts]. The skeletal and the dental maturity in a group of 189 children with cleft lip and/or cleft palate were determined by means of X-rays of the wrist joint and orthopantomogrammes. In 60 children, anthropometric determinations were also performed. 486 normal children involved in the Nijmegen growth study served as control subjects. The ages ranged from 4 to 14 years. A retardation in dental development was evidenced in boys with clefts. There was no remarkable difference in dental development between girls with clefts and girls without clefts. The progression in skeletal maturity was greater in girls with clefts than in girls without clefts. There was no remarkable difference in skeletal maturity between boys with clefts and normal boys. The determination of 10 anthropometric values revealed only a few remarkable differences between children with clefts and normal children."}
{"id": "PMID:232785", "title": "[Thyroid dysembryoma. Report of a case in an adult (author's transl)].", "content": "One case of dysembryoma of the thyroid gland is reported. 115 cases of that rare disease have been published; the tumor is particularly rare in adult (14 cases). Salient features are reviewed, mostly complications and malignant degeneration. Surgical removal is the only treatment and also the only mean to have histological diagnosis.", "contents": "[Thyroid dysembryoma. Report of a case in an adult (author's transl)]. One case of dysembryoma of the thyroid gland is reported. 115 cases of that rare disease have been published; the tumor is particularly rare in adult (14 cases). Salient features are reviewed, mostly complications and malignant degeneration. Surgical removal is the only treatment and also the only mean to have histological diagnosis."}
{"id": "PMID:232787", "title": "[Quantitative study of hepatic fibrosis in Hodgkin's disease (author's transl)].", "content": "The construction of a prototype apparatus adapted to the constraints of tissue structures has permitted not only the quantification of fibrosis within the liver but also analysis of its distribution. The cumulative histograms thus achieved permit the characterization of the liver in Hodgkin's disease.", "contents": "[Quantitative study of hepatic fibrosis in Hodgkin's disease (author's transl)]. The construction of a prototype apparatus adapted to the constraints of tissue structures has permitted not only the quantification of fibrosis within the liver but also analysis of its distribution. The cumulative histograms thus achieved permit the characterization of the liver in Hodgkin's disease."}
{"id": "PMID:232786", "title": "[Angina and \"normal coronarography\" results: diagnostic approach and future perspectives (author's transl)].", "content": "Patients with angina but with \"normal coronarography\" results, are not a rare finding during angiographic investigations, more especially in the case of women. The authors review the clinical, electrical, hemodynamic and metabolic characteristics of these cases, and discuss the principal known etiologies, and limits of \"normality\" with respect to coronary artery angiography results.", "contents": "[Angina and \"normal coronarography\" results: diagnostic approach and future perspectives (author's transl)]. Patients with angina but with \"normal coronarography\" results, are not a rare finding during angiographic investigations, more especially in the case of women. The authors review the clinical, electrical, hemodynamic and metabolic characteristics of these cases, and discuss the principal known etiologies, and limits of \"normality\" with respect to coronary artery angiography results."}
{"id": "PMID:232797", "title": "[Multilocular Paget's disease--a case report (author's transl)].", "content": "The simultaneous occurrence of Paget's disease in five different regions in a 76-year old woman is reported. Only one lesion exhibited the typical clinical appearance of this condition, whereas the others were diagnosed histologically. After radical surgical treatment of all lesions the patient has remained free from recurrence for more than three years.", "contents": "[Multilocular Paget's disease--a case report (author's transl)]. The simultaneous occurrence of Paget's disease in five different regions in a 76-year old woman is reported. Only one lesion exhibited the typical clinical appearance of this condition, whereas the others were diagnosed histologically. After radical surgical treatment of all lesions the patient has remained free from recurrence for more than three years."}
{"id": "PMID:232794", "title": "REM sleep and the prevention of endogenous depression.", "content": "The possibility of preventing endogenous depression may depend upon our understanding the brain mechanisms involved in the improvement of depression. Recent work in our laboratory has shed some light on these mechanisms. I will first describe this work and then suggest its possible preventive implications. Throughout this paper, the term depression means endogenous depression unless stated otherwise.", "contents": "REM sleep and the prevention of endogenous depression. The possibility of preventing endogenous depression may depend upon our understanding the brain mechanisms involved in the improvement of depression. Recent work in our laboratory has shed some light on these mechanisms. I will first describe this work and then suggest its possible preventive implications. Throughout this paper, the term depression means endogenous depression unless stated otherwise."}
{"id": "PMID:232795", "title": "REM sleep dependent release of vasotocin into cerebrospinal fluid of narcoleptics.", "content": "The lumbar cerebrospinal fluid (CSF) collected from 6 narcoleptic patients (three males and three females) aged between 31 and 47 years, as well as from 2 patients having Pickwickian syndromes with hypersomnia attacks (two males), aged 43-51 years, contained relatively high amounts of arginine vasotocin (AVT) only if the CSF was removed after a REM sleep period. The release was not induced by darkness since the same release of AVT occurred when the CSF was removed after a REM sleep period during daylight hours. No detectable AVT levels have been found in the CSF samples of four narcoleptics collected after a NREM period of sleep, either during night or daylight hours. The present results suggest a possible alteration of the rhythmical release of AVT both in narcolepsy and in narcoleptic syndromes.", "contents": "REM sleep dependent release of vasotocin into cerebrospinal fluid of narcoleptics. The lumbar cerebrospinal fluid (CSF) collected from 6 narcoleptic patients (three males and three females) aged between 31 and 47 years, as well as from 2 patients having Pickwickian syndromes with hypersomnia attacks (two males), aged 43-51 years, contained relatively high amounts of arginine vasotocin (AVT) only if the CSF was removed after a REM sleep period. The release was not induced by darkness since the same release of AVT occurred when the CSF was removed after a REM sleep period during daylight hours. No detectable AVT levels have been found in the CSF samples of four narcoleptics collected after a NREM period of sleep, either during night or daylight hours. The present results suggest a possible alteration of the rhythmical release of AVT both in narcolepsy and in narcoleptic syndromes."}
{"id": "PMID:232800", "title": "[Histological study of the teleost liver. III. The system of biliary pathways].", "content": "In the liver of Haplochromis burtoni four divisions of the intrahepatic biliary pathways can be distinguished: canaliculus, canaliculus ductulus transition, ductulus biliferus, ductus biliferus. There are no transitional stages between the hepatocytes and biliary epithelial cells. The results of the investigation suggest that the ductules open into the ducts in two ways, directly and by graded transition of structure. The first part of the ductulus has a very narrow lumen and therefore is similar to the \"Schaltst\u00fcck\" of salivary glands. Terminal ductulus cells can protrude into the canaliculus (= lumen of the liver tubulus), giving the appearance of centrotubular cells in cross-section. In the liver of most of the teleosts investigated here the canaliculi are intercellular. Tangentially cut diverticuli of the canaliculi appear to be unicellular (\"intracellular\") canaliculi, but are, however, merely unicellular (\"intracellular\") protrusions of the intercellular canaliculi. On the other hand the three cyprinid species (Barbus tetrazona, Idus idus, Carassius auratus) possess true unicellular (\"intracellular\") canaliculi. These can definitely be distinguished from the diverticuli of intercellular canaliculi by several criteria. Phylogenetically the unicellular (\"intracellular\") canaliculus must be regarded as derivative, and the intercellular canaliculus as the original form. The morphology of the wall of the gall-bladder of Haplochromis burtoni indicates that transfer of substances is increased together with transportation and drainage of fluids and variations in volume. The ultrastructure of the epithelial cells reveals a zonal arrangement.", "contents": "[Histological study of the teleost liver. III. The system of biliary pathways]. In the liver of Haplochromis burtoni four divisions of the intrahepatic biliary pathways can be distinguished: canaliculus, canaliculus ductulus transition, ductulus biliferus, ductus biliferus. There are no transitional stages between the hepatocytes and biliary epithelial cells. The results of the investigation suggest that the ductules open into the ducts in two ways, directly and by graded transition of structure. The first part of the ductulus has a very narrow lumen and therefore is similar to the \"Schaltst\u00fcck\" of salivary glands. Terminal ductulus cells can protrude into the canaliculus (= lumen of the liver tubulus), giving the appearance of centrotubular cells in cross-section. In the liver of most of the teleosts investigated here the canaliculi are intercellular. Tangentially cut diverticuli of the canaliculi appear to be unicellular (\"intracellular\") canaliculi, but are, however, merely unicellular (\"intracellular\") protrusions of the intercellular canaliculi. On the other hand the three cyprinid species (Barbus tetrazona, Idus idus, Carassius auratus) possess true unicellular (\"intracellular\") canaliculi. These can definitely be distinguished from the diverticuli of intercellular canaliculi by several criteria. Phylogenetically the unicellular (\"intracellular\") canaliculus must be regarded as derivative, and the intercellular canaliculus as the original form. The morphology of the wall of the gall-bladder of Haplochromis burtoni indicates that transfer of substances is increased together with transportation and drainage of fluids and variations in volume. The ultrastructure of the epithelial cells reveals a zonal arrangement."}
{"id": "PMID:232803", "title": "[Gartner's duct carcinoma of vagina in pregnancy - case report (author's transl)].", "content": "Reported in this paper is a mesonephroid carcinoma in the vagina of a primigravida, 27 years of age, in the 27th or 28th week of pregnancy. The carcionoma originated from Gartner's duct and is characterised by typical papillary structures. Such carcionoma quite often cannot be morphologically differentiated from metamesonephroid carcionomas which originate from Mueller's epithelium to occur on the same site. Both tumour forms are rather often be considered an entity in relevant literature. The development of that carcinoma during gravidity is considered accidental. - Included in the therapeutic approach were Caesarean section, radical hysterectomy, including radical adnexectomy and removal of a 5-cm vaginal collar, removal of the Douglas peritoneum because of visible intraperitoneal metastasation, and extensive lymphonodectomy, all in one session. - Biaxial telecobalt pendulum irradiation followed postsurgically, the focal dose being 7,000 rd. No sign of recurrence has been recordable from follow-up checks and clinical examinations, one year from surgery.", "contents": "[Gartner's duct carcinoma of vagina in pregnancy - case report (author's transl)]. Reported in this paper is a mesonephroid carcinoma in the vagina of a primigravida, 27 years of age, in the 27th or 28th week of pregnancy. The carcionoma originated from Gartner's duct and is characterised by typical papillary structures. Such carcionoma quite often cannot be morphologically differentiated from metamesonephroid carcionomas which originate from Mueller's epithelium to occur on the same site. Both tumour forms are rather often be considered an entity in relevant literature. The development of that carcinoma during gravidity is considered accidental. - Included in the therapeutic approach were Caesarean section, radical hysterectomy, including radical adnexectomy and removal of a 5-cm vaginal collar, removal of the Douglas peritoneum because of visible intraperitoneal metastasation, and extensive lymphonodectomy, all in one session. - Biaxial telecobalt pendulum irradiation followed postsurgically, the focal dose being 7,000 rd. No sign of recurrence has been recordable from follow-up checks and clinical examinations, one year from surgery."}
{"id": "PMID:232796", "title": "Pineal vasotocin: REM sleep dependent release into cerebrospinal fluid of man.", "content": "Lumbar cerebrospinal fluid (CSF) of seven healthy male volunteers contains detectable levels of arginine vasotocin (AVT) when CSF was removed after awakening from rapid eye movement (REM) sleep. No detectable levels of AVT were found in the CSF of the same subjects when CSF WAS removed after awakening from non rapid eye movement (NREM) sleep. The amount of AVT detected in CSF after REM sleep was significantly higher if the subjects experienced vivid and emotive dreams. The present results provide the first evidence for a REM sleep dependent release of AVT into CSF of man.", "contents": "Pineal vasotocin: REM sleep dependent release into cerebrospinal fluid of man. Lumbar cerebrospinal fluid (CSF) of seven healthy male volunteers contains detectable levels of arginine vasotocin (AVT) when CSF was removed after awakening from rapid eye movement (REM) sleep. No detectable levels of AVT were found in the CSF of the same subjects when CSF WAS removed after awakening from non rapid eye movement (NREM) sleep. The amount of AVT detected in CSF after REM sleep was significantly higher if the subjects experienced vivid and emotive dreams. The present results provide the first evidence for a REM sleep dependent release of AVT into CSF of man."}
{"id": "PMID:232807", "title": "Influence of gallamine, pancuronium, d-tubocurarine and succinylcholine on adrenergic neurotransmission.", "content": "The influence of gallamine, pancuronium, d-tubocurarine and succinylcholine on adrenergic neurotransmission was studied in the isolated saphenous vein of the dog. Pancuronium increased the response of vascular smooth muscle to adrenergic nerve stimulation and to exogenous norepinephrine; gallamine, d-tubocurarine and succinylcholine had no effect. The relaxation caused by small doses of acetylcholine added during sympathetic nerve stimulation (prejunctional effect), was inhibited by pancuronium and by gallamine. In vein strips, charged with (3H) norepinephrine, acetylcholine inhibits the catecholamine-efflux evoked by sympathetic nerve stimulation. That inhibition was abolished by gallamine. This confirms that gallamine inhibits the prejunctional effect of acetylcholine on adrenergic neurotransmission. When extrapolated to the intact organism, this means that gallamine and pancuronium will augment the release of norepinephrine by acting as muscarinic antagonists also at prejunctional receptor sites in tissues exposed to combined sympathetic and vagal nerve activity. This mechanism would explain in part the cardiovascular effects of these muscle relaxants.", "contents": "Influence of gallamine, pancuronium, d-tubocurarine and succinylcholine on adrenergic neurotransmission. The influence of gallamine, pancuronium, d-tubocurarine and succinylcholine on adrenergic neurotransmission was studied in the isolated saphenous vein of the dog. Pancuronium increased the response of vascular smooth muscle to adrenergic nerve stimulation and to exogenous norepinephrine; gallamine, d-tubocurarine and succinylcholine had no effect. The relaxation caused by small doses of acetylcholine added during sympathetic nerve stimulation (prejunctional effect), was inhibited by pancuronium and by gallamine. In vein strips, charged with (3H) norepinephrine, acetylcholine inhibits the catecholamine-efflux evoked by sympathetic nerve stimulation. That inhibition was abolished by gallamine. This confirms that gallamine inhibits the prejunctional effect of acetylcholine on adrenergic neurotransmission. When extrapolated to the intact organism, this means that gallamine and pancuronium will augment the release of norepinephrine by acting as muscarinic antagonists also at prejunctional receptor sites in tissues exposed to combined sympathetic and vagal nerve activity. This mechanism would explain in part the cardiovascular effects of these muscle relaxants."}
{"id": "PMID:232808", "title": "Determination of enzyme activity by chromatography and videodensitometry. II. Urea cycle enzymes in tissue homogenates.", "content": "Methods are described for the determination of the activity of urea cycle enzymes in human and rat tissues by chromatography and videodensitometry(CV-technique). With specific substrates carbamoyl-phosphate synthetase and ornithine carbamoyltransferase activities were determined as the amounts of citrulline formed. Argininosuccinate synthetase, argininosuccinate lyase and arginase activities were measured from the changes in ornithine concentration. For measuring the activity of five enzymes 5 to 10 mg wet weight of tissue was sufficient. The CV-technique could be conveniently applied for the investigation of enzyme content in samples from human biopsy.", "contents": "Determination of enzyme activity by chromatography and videodensitometry. II. Urea cycle enzymes in tissue homogenates. Methods are described for the determination of the activity of urea cycle enzymes in human and rat tissues by chromatography and videodensitometry(CV-technique). With specific substrates carbamoyl-phosphate synthetase and ornithine carbamoyltransferase activities were determined as the amounts of citrulline formed. Argininosuccinate synthetase, argininosuccinate lyase and arginase activities were measured from the changes in ornithine concentration. For measuring the activity of five enzymes 5 to 10 mg wet weight of tissue was sufficient. The CV-technique could be conveniently applied for the investigation of enzyme content in samples from human biopsy."}
{"id": "PMID:232809", "title": "Myofibrillar proteins, enzyme activity and fibre types in human skeletal muscle.", "content": "The myofibrillar proteins and relative LC-3 content of myofibrils prepared from five different, left and right muscles of the human forearm were studied by electrophoresis in 10% SDS-polyacrylamide gels followed by densitometry. The specific K-activated ATPase activity of the myofibrillar myosin of the myofibrils was determined and the distribution of the fibre types was analyzed by histochemical methods. The qualitative pattern of the myofibrillar proteins was found to be identical in the different muscles; in the other parameters, however, a variation in a narrow range was observed. The relative LC-3 content, the ATPase activity and the type II fibre content of the right side muscles were always higher than those of the corresponding left side muscles.", "contents": "Myofibrillar proteins, enzyme activity and fibre types in human skeletal muscle. The myofibrillar proteins and relative LC-3 content of myofibrils prepared from five different, left and right muscles of the human forearm were studied by electrophoresis in 10% SDS-polyacrylamide gels followed by densitometry. The specific K-activated ATPase activity of the myofibrillar myosin of the myofibrils was determined and the distribution of the fibre types was analyzed by histochemical methods. The qualitative pattern of the myofibrillar proteins was found to be identical in the different muscles; in the other parameters, however, a variation in a narrow range was observed. The relative LC-3 content, the ATPase activity and the type II fibre content of the right side muscles were always higher than those of the corresponding left side muscles."}
{"id": "PMID:232810", "title": "The study of nitroxide radical active esters as spin labels on muscle protein actin.", "content": "Nitroxide radical active esters were used to label the muscle protein actin and to study the orientation dependence of the EPR spectra of the labelled protein. It is concluded that the labels are located at least at two different sites of the protein with strong polar environment and different mobilities. The EPR spectrum of the strongly immobilized labels exhibits orientation dependence, the N--O bond axis of the spin labels is nearly perpendicular to the long axis of the F-actin threads, and the labels undergo a rapid rotational motion about an axis directed perpendicular to the filament axis. The application of the nitroxide radical active esters may be useful in the study of ordered systems as muscle or muscle protein systems.", "contents": "The study of nitroxide radical active esters as spin labels on muscle protein actin. Nitroxide radical active esters were used to label the muscle protein actin and to study the orientation dependence of the EPR spectra of the labelled protein. It is concluded that the labels are located at least at two different sites of the protein with strong polar environment and different mobilities. The EPR spectrum of the strongly immobilized labels exhibits orientation dependence, the N--O bond axis of the spin labels is nearly perpendicular to the long axis of the F-actin threads, and the labels undergo a rapid rotational motion about an axis directed perpendicular to the filament axis. The application of the nitroxide radical active esters may be useful in the study of ordered systems as muscle or muscle protein systems."}
{"id": "PMID:232811", "title": "Central mediation of hormonal influences on instrumental avoidance conditioning.", "content": "Two behaviorally active hormones of the pituitary-adrenal system are adrenocorticotropic hormones (ACTH) and corticosterone, and their behavioral effects are facilitation and inhibition of performance of previously learned avoidance responses, respectively. Their uptake, distribution and effects on central nervous system are reviewed. Hypothalamic neurotransmitter control of corticotropin releasing hormone (CRH) is described together with hypothalamic and extra-hypothalamic (hippocampal) regulation of pituitary-adrenal activity. Extra-hypothalamic mediation of the behavioral effects of ACTH is evaluated. Recent isotopic mappings of the efferents of the hippocampal formation have identified pathways from hippocampal subiculum to hypothalamus and posterior lateral and anterior thalamic nuclei. The evidence reviewed suggests a complex circuit involving hippocampal subiculum, thalamus and hypothalamus may be involved both in regulating pituitary-adrenal responses to stress and in mediating the effects of ACTH on avoidance behavior.", "contents": "Central mediation of hormonal influences on instrumental avoidance conditioning. Two behaviorally active hormones of the pituitary-adrenal system are adrenocorticotropic hormones (ACTH) and corticosterone, and their behavioral effects are facilitation and inhibition of performance of previously learned avoidance responses, respectively. Their uptake, distribution and effects on central nervous system are reviewed. Hypothalamic neurotransmitter control of corticotropin releasing hormone (CRH) is described together with hypothalamic and extra-hypothalamic (hippocampal) regulation of pituitary-adrenal activity. Extra-hypothalamic mediation of the behavioral effects of ACTH is evaluated. Recent isotopic mappings of the efferents of the hippocampal formation have identified pathways from hippocampal subiculum to hypothalamus and posterior lateral and anterior thalamic nuclei. The evidence reviewed suggests a complex circuit involving hippocampal subiculum, thalamus and hypothalamus may be involved both in regulating pituitary-adrenal responses to stress and in mediating the effects of ACTH on avoidance behavior."}
{"id": "PMID:232812", "title": "Relationships between phenomena of paradoxical sleep and their counterparts in wakefulness.", "content": "Our studies suggest that paradoxical sleep is a state in which the brainstem is in a functional mode normally associated with presentations of novel stimuli. Furthermore, the combination of atonia and an internal state of activation indicates sustained activity of a brainstem mechanism designed to dampen responses to sudden, novel stimuli in wakefulness lest the animal over react and run blindly into danger prior to stimulus analysis. This conclusion stems from two sets of data. Studies of large-amplitude waves, which characteristically occur spontaneously just prior to and during paradoxical sleep, have demonstrated that the waves are signs of alerting. These waves, termed ponto-geniculooccipital (PGO) spikes, can be induced during both slow wave and paradoxical sleep by external stimuli at a threshold below actual arousal. Whenever cats are confronted with novel stimuli during wakefulness, eye movement potentials, which are recorded from the same sites as PGO spikes but differ from them in several characteristics, assume all the characteristics of PGO spikes. These observations indicate that the central nervous system during paradoxical sleep is in a \"peculiar\" state of activation which is not behaviorally expressed. Other experiments have focused on the muscle atonia of paradoxical sleep. Small, bilateral dorsolateral pontine tegmental lesions create the dramatic phenomenon of paradoxical sleep without atonia which is characterized as follows: After slow wave sleep, when paradoxical sleep with muscle atonia would normally appear, cats raise their heads, make body righting movements, exhibit alternating movements of the limbs, and even attempt to stand. Throughout an episode, which shows all other aspects of paradoxical sleep, including unresponsiveness to visual stimuli, cats act as if they are being startled, searching and sometimes attacking an object. In wakefulness they show minor cerebellar signs. Presumably the lesions disrupt both the pontine excitation of the medullary inhibitory area and the inhibition of a brainstem system for mobilizing activity normally in force during paradoxical sleep. Studies of the same cats during wakefulness have shown that there in an increase in exploratory locomotor activity of 23 to 127 percent as measured in an open-field test. The existence of parallel effects on motor control in wakefulness and paradoxical sleep produced by pontine lesions suggests that the atonia of paradoxical sleep is a reflection of excessive activity of a brainstem response dampening mechanism which operates more subtly during wakefulness to produce appropriately modulated responses to various unexpected stimuli.", "contents": "Relationships between phenomena of paradoxical sleep and their counterparts in wakefulness. Our studies suggest that paradoxical sleep is a state in which the brainstem is in a functional mode normally associated with presentations of novel stimuli. Furthermore, the combination of atonia and an internal state of activation indicates sustained activity of a brainstem mechanism designed to dampen responses to sudden, novel stimuli in wakefulness lest the animal over react and run blindly into danger prior to stimulus analysis. This conclusion stems from two sets of data. Studies of large-amplitude waves, which characteristically occur spontaneously just prior to and during paradoxical sleep, have demonstrated that the waves are signs of alerting. These waves, termed ponto-geniculooccipital (PGO) spikes, can be induced during both slow wave and paradoxical sleep by external stimuli at a threshold below actual arousal. Whenever cats are confronted with novel stimuli during wakefulness, eye movement potentials, which are recorded from the same sites as PGO spikes but differ from them in several characteristics, assume all the characteristics of PGO spikes. These observations indicate that the central nervous system during paradoxical sleep is in a \"peculiar\" state of activation which is not behaviorally expressed. Other experiments have focused on the muscle atonia of paradoxical sleep. Small, bilateral dorsolateral pontine tegmental lesions create the dramatic phenomenon of paradoxical sleep without atonia which is characterized as follows: After slow wave sleep, when paradoxical sleep with muscle atonia would normally appear, cats raise their heads, make body righting movements, exhibit alternating movements of the limbs, and even attempt to stand. Throughout an episode, which shows all other aspects of paradoxical sleep, including unresponsiveness to visual stimuli, cats act as if they are being startled, searching and sometimes attacking an object. In wakefulness they show minor cerebellar signs. Presumably the lesions disrupt both the pontine excitation of the medullary inhibitory area and the inhibition of a brainstem system for mobilizing activity normally in force during paradoxical sleep. Studies of the same cats during wakefulness have shown that there in an increase in exploratory locomotor activity of 23 to 127 percent as measured in an open-field test. The existence of parallel effects on motor control in wakefulness and paradoxical sleep produced by pontine lesions suggests that the atonia of paradoxical sleep is a reflection of excessive activity of a brainstem response dampening mechanism which operates more subtly during wakefulness to produce appropriately modulated responses to various unexpected stimuli."}
{"id": "PMID:232818", "title": "Modulation of T cells and macrophages by cholera toxin treatment in vivo and in vitro.", "content": "Cholera Toxin influences the antibody response to SRBC. Enhanced responses occur in vivo and in vitro when CT is added together with antigen. However, CT depresses antibody formation when given in vivo before antigen but enhances in vitro responses under the same conditions. Modulation of antibody formation appeared due to effects of T lymphocytes as well as macrophages. Co-cultivation of immunologically impaired spleen cells from CT pretreated animals with macrophage-rich peritoneal cells or educated T cells increased the antibody response.", "contents": "Modulation of T cells and macrophages by cholera toxin treatment in vivo and in vitro. Cholera Toxin influences the antibody response to SRBC. Enhanced responses occur in vivo and in vitro when CT is added together with antigen. However, CT depresses antibody formation when given in vivo before antigen but enhances in vitro responses under the same conditions. Modulation of antibody formation appeared due to effects of T lymphocytes as well as macrophages. Co-cultivation of immunologically impaired spleen cells from CT pretreated animals with macrophage-rich peritoneal cells or educated T cells increased the antibody response."}
{"id": "PMID:232822", "title": "Tobacco smoke and the pulmonary alveolar macrophage.", "content": "Our results indicate that tobacco smoke exposure to varying duration causes morphological, biochemical and functional alterations in pulmonary alveolar macrophages. The results of these changes is a population of alveolar macrophages made up of larger cells, with a reduced nucleus-cytoplasmic ratio, which are heavily loaded with heterolysosomes containing lipid. Though their fractional complement of mitochondria remains the same, an increase in the inner mitochondrial membrane surface area may be related to an enhanced oxidative metabolism. The cell is biochemically activated particularly following chronic exposure and is functionally impaired with respect to phagocytosis.", "contents": "Tobacco smoke and the pulmonary alveolar macrophage. Our results indicate that tobacco smoke exposure to varying duration causes morphological, biochemical and functional alterations in pulmonary alveolar macrophages. The results of these changes is a population of alveolar macrophages made up of larger cells, with a reduced nucleus-cytoplasmic ratio, which are heavily loaded with heterolysosomes containing lipid. Though their fractional complement of mitochondria remains the same, an increase in the inner mitochondrial membrane surface area may be related to an enhanced oxidative metabolism. The cell is biochemically activated particularly following chronic exposure and is functionally impaired with respect to phagocytosis."}
{"id": "PMID:232826", "title": "[Hereditary abnormalities of galactose metabolism: diagnosis and biochemical supervision (author's transl)].", "content": "The authors define the main stages of the biochemical study of hereditary abnormalities of galactose metabolism. They review laboratory examinations for detection, enzyme examinations which provide the diagnostic proof, further examinations which permit one to follow the course and efficacy of a galactose-free diet, the demonstration of genetic variants, the technics of antenatal diagnosis and routine neonatal detection.", "contents": "[Hereditary abnormalities of galactose metabolism: diagnosis and biochemical supervision (author's transl)]. The authors define the main stages of the biochemical study of hereditary abnormalities of galactose metabolism. They review laboratory examinations for detection, enzyme examinations which provide the diagnostic proof, further examinations which permit one to follow the course and efficacy of a galactose-free diet, the demonstration of genetic variants, the technics of antenatal diagnosis and routine neonatal detection."}
{"id": "PMID:232830", "title": "[Cell-mediated cytotoxicity against Rous sarcoma in the hamster (author's transl)].", "content": "The cytotoxic response of lymphoid cells from hamsters immunized against RS 2/3 cells, transformed by Rous sarcoma virus, was investigated. The highest cytotoxic response was obtained after the third inoculation of RS 2/3 cells. Both the non-tumor-bearing hamsters immunized with physically or chemically treated RS 2/3 cells and the tumor-bearing hamsters, grafted with live RS 2/3 cells provided splenic cytotoxic lymphoid cells. On the contrary, lymphoid cells obtained from lymph nodes were only slightly cytotoxic. The results did not permit to establish a relationship between the cytotoxic activity of the lymphoid cells obtained from the spleen and from the lymph nodes. The cytotoxic response of lymphoid cells in vitro was not correlated with tumor rejection, in vivo.", "contents": "[Cell-mediated cytotoxicity against Rous sarcoma in the hamster (author's transl)]. The cytotoxic response of lymphoid cells from hamsters immunized against RS 2/3 cells, transformed by Rous sarcoma virus, was investigated. The highest cytotoxic response was obtained after the third inoculation of RS 2/3 cells. Both the non-tumor-bearing hamsters immunized with physically or chemically treated RS 2/3 cells and the tumor-bearing hamsters, grafted with live RS 2/3 cells provided splenic cytotoxic lymphoid cells. On the contrary, lymphoid cells obtained from lymph nodes were only slightly cytotoxic. The results did not permit to establish a relationship between the cytotoxic activity of the lymphoid cells obtained from the spleen and from the lymph nodes. The cytotoxic response of lymphoid cells in vitro was not correlated with tumor rejection, in vivo."}
{"id": "PMID:232832", "title": "Effect of dexamethasone and ACTH on the secretion pattern of fractionated 17-ketosteroids in hirsutism.", "content": "Urinary steroid fractionations of 17-ketosteroids were carried out in 3 normally-ovulating young women and in 2 women with hirsutism. Dehydroepiandrosterone, aetiocholanolone, androsterone, 11 beta-hydroxyaetiocholanolone, 11 beta-hydroxyandrosterone, 11-oxoaetiocholanolone and 11-oxondrosterone were determined quantitatively by paper chromatography. Both patients had decreased levels of 11-deoxy and 11-oxy-17-ketosteroids compared with the normals. The ready suppression of 11-oxy-17-ketosteroids and the poor suppression of 11-deoxy-17-ketosteroids by dexamethasone in both patients suggests an ovarian origin of 11-deoxy-17-ketosteroids. Supporting evidence for an ovarian origin in Case 1 was furnished by the poor suppression of testosterone by dexamethasone and lack of response to ACTH stimulation of the adrenal glands. The presented data emphasize that the precursor of 11-deoxy-17-ketosteroids of ovarian origin, possibly testosterone, may well be the cause of hirsutism in both patients.", "contents": "Effect of dexamethasone and ACTH on the secretion pattern of fractionated 17-ketosteroids in hirsutism. Urinary steroid fractionations of 17-ketosteroids were carried out in 3 normally-ovulating young women and in 2 women with hirsutism. Dehydroepiandrosterone, aetiocholanolone, androsterone, 11 beta-hydroxyaetiocholanolone, 11 beta-hydroxyandrosterone, 11-oxoaetiocholanolone and 11-oxondrosterone were determined quantitatively by paper chromatography. Both patients had decreased levels of 11-deoxy and 11-oxy-17-ketosteroids compared with the normals. The ready suppression of 11-oxy-17-ketosteroids and the poor suppression of 11-deoxy-17-ketosteroids by dexamethasone in both patients suggests an ovarian origin of 11-deoxy-17-ketosteroids. Supporting evidence for an ovarian origin in Case 1 was furnished by the poor suppression of testosterone by dexamethasone and lack of response to ACTH stimulation of the adrenal glands. The presented data emphasize that the precursor of 11-deoxy-17-ketosteroids of ovarian origin, possibly testosterone, may well be the cause of hirsutism in both patients."}
{"id": "PMID:232833", "title": "[Twin pregnancy following bromocriptine in an acromegalic patient staying sterile after removal of a pituitary adenoma. Immunocytochemical study of the tumor (author's transl)].", "content": "A pituitary adenoma was removed from a young woman who had acromegaly with galactorrhea-amenorrhea. Postoperatively, the dysmorphic acromegalic syndrome and galactorrhea decreased but amenorrhea, elevated serum GH and PRL concentrations remained. After Bromocriptine administration (5 mg daily) GH and PRL levels became normal, vaginal bleeding ensued within 3 months and a twin pregnancy was induced. An immunocytochemical study of the pituitary adenoma revealed the presence of two well defined, distinct cell types, each secreting one hormone with large preponderance of GH cells.", "contents": "[Twin pregnancy following bromocriptine in an acromegalic patient staying sterile after removal of a pituitary adenoma. Immunocytochemical study of the tumor (author's transl)]. A pituitary adenoma was removed from a young woman who had acromegaly with galactorrhea-amenorrhea. Postoperatively, the dysmorphic acromegalic syndrome and galactorrhea decreased but amenorrhea, elevated serum GH and PRL concentrations remained. After Bromocriptine administration (5 mg daily) GH and PRL levels became normal, vaginal bleeding ensued within 3 months and a twin pregnancy was induced. An immunocytochemical study of the pituitary adenoma revealed the presence of two well defined, distinct cell types, each secreting one hormone with large preponderance of GH cells."}
{"id": "PMID:232834", "title": "[Adrenocortical function in hyperprolactinemia. The study of glucocorticoids, mineralocorticoids and androgens in chronic and acute hyperprolactinemias (author's transl)].", "content": "Glucocorticoids, mineralocorticoids, and adrenal androgens were studied in 3 groups of patients: control subjects (group I), hyperprolactinemic subjects (group II) and miscellaneous patients including chromophobe adenomas and normalized hyperprolactinemic subjects treated with Bromocriptine (group III). All the patients were studied in the basal state and under various conditions: Metyrapone, ACTH, TRH for glucocorticoids, ACTH, TRH, saline perfusion for mineralocorticoids, ACTH and TRH for androgens. It is concluded that: the adrenal secretion of glucocorticoids, mineralocorticoids and androgens is not altered under basal conditions in chronic hyperprolactinemia nor during dynamic tests in chronic hyperprolactinemia (prolactin adenoma) nor in acute hyperprolactinemia (induced by TRH).", "contents": "[Adrenocortical function in hyperprolactinemia. The study of glucocorticoids, mineralocorticoids and androgens in chronic and acute hyperprolactinemias (author's transl)]. Glucocorticoids, mineralocorticoids, and adrenal androgens were studied in 3 groups of patients: control subjects (group I), hyperprolactinemic subjects (group II) and miscellaneous patients including chromophobe adenomas and normalized hyperprolactinemic subjects treated with Bromocriptine (group III). All the patients were studied in the basal state and under various conditions: Metyrapone, ACTH, TRH for glucocorticoids, ACTH, TRH, saline perfusion for mineralocorticoids, ACTH and TRH for androgens. It is concluded that: the adrenal secretion of glucocorticoids, mineralocorticoids and androgens is not altered under basal conditions in chronic hyperprolactinemia nor during dynamic tests in chronic hyperprolactinemia (prolactin adenoma) nor in acute hyperprolactinemia (induced by TRH)."}
{"id": "PMID:232835", "title": "[Immunocytochemical similarities between basophilic and chromophobe pituitary adenomas. Light and electron microscopic study of 13 cases (author's transl)].", "content": "ACTH, beta MSH, beta LPH, beta endorpSin, leucine and methionine enkephalin activities were tested in four Cushing pituitary basophilic adenomas and nine \"chromophobe\" adenomas with immunoperoxidase methods. The antisera gave various positive reactions in both of these groups. ACTH, alpha MSH and enkephalins were predominant. The reason why these hormones are clinically silent in \"chromophobe\" or, even, basophilic adenomas is still to be elucidated.", "contents": "[Immunocytochemical similarities between basophilic and chromophobe pituitary adenomas. Light and electron microscopic study of 13 cases (author's transl)]. ACTH, beta MSH, beta LPH, beta endorpSin, leucine and methionine enkephalin activities were tested in four Cushing pituitary basophilic adenomas and nine \"chromophobe\" adenomas with immunoperoxidase methods. The antisera gave various positive reactions in both of these groups. ACTH, alpha MSH and enkephalins were predominant. The reason why these hormones are clinically silent in \"chromophobe\" or, even, basophilic adenomas is still to be elucidated."}
{"id": "PMID:232836", "title": "[Pituitary adenomas with cells containing b\u00eata MSH, alpha and b\u00eata endorphins and without ACTH (author's transl)].", "content": "By using immunohistoenzymatic techniques, cells of 4 pituitary adenomas are revealed with beta MSH, alpha and beta endorphins antisera but do not react with 1--24 and 17--39 ACTH antisera. These data suggest that adenomatous cells are able to synthesize and LPH-like molecule without ACTH. The levels of plasmatic LPH and beta MSH, studied by RIA, stay normal. These results are discussed.", "contents": "[Pituitary adenomas with cells containing b\u00eata MSH, alpha and b\u00eata endorphins and without ACTH (author's transl)]. By using immunohistoenzymatic techniques, cells of 4 pituitary adenomas are revealed with beta MSH, alpha and beta endorphins antisera but do not react with 1--24 and 17--39 ACTH antisera. These data suggest that adenomatous cells are able to synthesize and LPH-like molecule without ACTH. The levels of plasmatic LPH and beta MSH, studied by RIA, stay normal. These results are discussed."}
{"id": "PMID:232837", "title": "[A feminizing adrenal carcinoma in man: in vivo and in vitro study (author's transl)].", "content": "A 31 years old man with an adrenocortical carcinoma was studied. Clinically he had a bilateral and recidiving gynecomastia and showed high urinary oestrogens, 17 cetosteroids, tetra-hydro-desoxy-cortisol and pregnandiol excretion with normal cortisol production. A partial increase on ACTH, no suppression on dexamethasone and no variation on HCG administration were observed. The surgical resection of the tumor normalized this urinary excretion. The serum dehydro-epiandrosterone (DHEA) and sulfate (DHEAS), oestrone, oestradiol, androstenedione (A) levels were greatly elevated. No variations of the cortisol, A, DHEA and DHEAS was noted after ACTH injection. In vitro the lack of ACTH's action was related to an anomaly of ACTH receptor with normal protein kinase activity.", "contents": "[A feminizing adrenal carcinoma in man: in vivo and in vitro study (author's transl)]. A 31 years old man with an adrenocortical carcinoma was studied. Clinically he had a bilateral and recidiving gynecomastia and showed high urinary oestrogens, 17 cetosteroids, tetra-hydro-desoxy-cortisol and pregnandiol excretion with normal cortisol production. A partial increase on ACTH, no suppression on dexamethasone and no variation on HCG administration were observed. The surgical resection of the tumor normalized this urinary excretion. The serum dehydro-epiandrosterone (DHEA) and sulfate (DHEAS), oestrone, oestradiol, androstenedione (A) levels were greatly elevated. No variations of the cortisol, A, DHEA and DHEAS was noted after ACTH injection. In vitro the lack of ACTH's action was related to an anomaly of ACTH receptor with normal protein kinase activity."}
{"id": "PMID:232840", "title": "[Studies of necrotizing enteritis of suckling piglets (Clostridium perfringens type C enterotoxemia) in industrialized sow breeding units. 4. Epizootiology].", "content": "Necrotising enteritis had been the cause of death of 4.9 per cent in 5,177 nursed piglets, which was established by pathological examination. The number of piglets, in that context, which had come from industrialised sow breeding units was equivalent to 92 per cent. The nursed piglet held the third position, next to smaller ruminants (19.4 per cent) and fowl (6.0 per cent), with regard to the occurrence of Clostridium perfringens enterotoxemia or necrotising enteritis in 112,218 animals which were pathologically examined after death. Necrotising enteritis so far has been rare in the GDR. No regional accumulation has been observed. Several outbreaks on industrialised sow breeding units actually remained stationary. The occurrence of the disease may be favoured by a number of factors which are conducive to accumulation of Clostridium perfringens Type C in a given stock. Group keeping of pregnant sows, simultaneous farrowing of larger groups of sows, group treatment of nursed piglets, using neomycin, chloramphenicol, oxytetracycline, and other antibiotics to which Clostridium perfringens is primarily resistant or has acquired resistance in the course of time are some of those contributive factors. Transmission of Clostridium perfringens Type C through feedstuff is possible, though it would lead to a real outbreak only by high intensity of the contamination, and it played a minor role in proliferation of the disease. 3479 Clostridium perfringens strains were isolated from 9,481 animals, both clinically intact and after death, with 30 species being included. Type classification revealed 2454 strains of Type A (70 per cent), 204 of Type D (5.88 per cent), 164 of Type C (four per cent), and 48 of Type B (1.34 per cent). There were 688 atoxic strains (17 per cent). Swine is the major carrier of Clostridium perfringens Type C, with 87 per cent of all Clostridium perfringens Type C strains having been isolated from swine. Swine was followed by fowl (four per cent), sheep (four per cent), cattle, rabbit, and dog (1.27 per cent each). Clostridium perfringens Type C was obtained from the faeces of clinically intact sows in seven instances, including two cases with sows (0.46 per cent) from farms with no previous record of necrotising enteritis.", "contents": "[Studies of necrotizing enteritis of suckling piglets (Clostridium perfringens type C enterotoxemia) in industrialized sow breeding units. 4. Epizootiology]. Necrotising enteritis had been the cause of death of 4.9 per cent in 5,177 nursed piglets, which was established by pathological examination. The number of piglets, in that context, which had come from industrialised sow breeding units was equivalent to 92 per cent. The nursed piglet held the third position, next to smaller ruminants (19.4 per cent) and fowl (6.0 per cent), with regard to the occurrence of Clostridium perfringens enterotoxemia or necrotising enteritis in 112,218 animals which were pathologically examined after death. Necrotising enteritis so far has been rare in the GDR. No regional accumulation has been observed. Several outbreaks on industrialised sow breeding units actually remained stationary. The occurrence of the disease may be favoured by a number of factors which are conducive to accumulation of Clostridium perfringens Type C in a given stock. Group keeping of pregnant sows, simultaneous farrowing of larger groups of sows, group treatment of nursed piglets, using neomycin, chloramphenicol, oxytetracycline, and other antibiotics to which Clostridium perfringens is primarily resistant or has acquired resistance in the course of time are some of those contributive factors. Transmission of Clostridium perfringens Type C through feedstuff is possible, though it would lead to a real outbreak only by high intensity of the contamination, and it played a minor role in proliferation of the disease. 3479 Clostridium perfringens strains were isolated from 9,481 animals, both clinically intact and after death, with 30 species being included. Type classification revealed 2454 strains of Type A (70 per cent), 204 of Type D (5.88 per cent), 164 of Type C (four per cent), and 48 of Type B (1.34 per cent). There were 688 atoxic strains (17 per cent). Swine is the major carrier of Clostridium perfringens Type C, with 87 per cent of all Clostridium perfringens Type C strains having been isolated from swine. Swine was followed by fowl (four per cent), sheep (four per cent), cattle, rabbit, and dog (1.27 per cent each). Clostridium perfringens Type C was obtained from the faeces of clinically intact sows in seven instances, including two cases with sows (0.46 per cent) from farms with no previous record of necrotising enteritis."}
{"id": "PMID:232841", "title": "[Studies of necrotizing enteritis of suckling piglets (Clostridium perfringens type C enterotoxemia) in industrialized sow breeding units. 5. Control of the disease].", "content": "Recent methods used and experience obtained in the control of necrotising enteritis are reported in this paper, with reference being made to both the pathogenesis and epizootiology of the disease. Two inoculations of the sows, using \"Enterotox\u00e4mievakzine Dessau bivalent\" five and three weeks before parturition, have worked well for prophylaxis. Oral treatment was applied to nursed piglets, using 40,000 I.U. of \"Aviapen\" and \"V-Tablopen\" penicillin per animal and day over periods between two and four days, helped to minimise piglet loss, particularly in the period between a fresh outbreak and full effectiveness of immunoprophylactic action. Such treatment was conducted metaphylactically and therapeutically. The first metaphylactic treatment was given within 24 hours from parturition. Combination of mother animal vaccination with the above therapeutic use of those two penicillin preparations worked extremely well in enzootically contaminated stocks and proved to be the most effective approach, for the time being, to controlling necrotising enteritis of nursed piglets. Yet, all those control measures failed to bring about full stock sanitation on industrialised units. Sow trading was not permitted until at least four weeks had elapsed from full effectiveness of mother animal vaccination, with the view to reducing the proliferation of Clostridium perfringens Type C via sales of breeding animals. All sows were given two \"Enterotox\u00e4mievakzine Dessau bivalent\" vaccinations, prior to sale. The animals were sold only to smaller farms (less than 500 sows for breeding) with concentional keeping patterns which were kept under constant diagnostic supervision. Neomycin, oxytetracycline, chloramphenicol, and other antibiotics against which Clostridium perfringens was resistant or in a position to assume resistance were used on endangered stocks only in conjunction with penicillin or not at all. This programme of control has proved to be efficient through a period of more than three years.", "contents": "[Studies of necrotizing enteritis of suckling piglets (Clostridium perfringens type C enterotoxemia) in industrialized sow breeding units. 5. Control of the disease]. Recent methods used and experience obtained in the control of necrotising enteritis are reported in this paper, with reference being made to both the pathogenesis and epizootiology of the disease. Two inoculations of the sows, using \"Enterotox\u00e4mievakzine Dessau bivalent\" five and three weeks before parturition, have worked well for prophylaxis. Oral treatment was applied to nursed piglets, using 40,000 I.U. of \"Aviapen\" and \"V-Tablopen\" penicillin per animal and day over periods between two and four days, helped to minimise piglet loss, particularly in the period between a fresh outbreak and full effectiveness of immunoprophylactic action. Such treatment was conducted metaphylactically and therapeutically. The first metaphylactic treatment was given within 24 hours from parturition. Combination of mother animal vaccination with the above therapeutic use of those two penicillin preparations worked extremely well in enzootically contaminated stocks and proved to be the most effective approach, for the time being, to controlling necrotising enteritis of nursed piglets. Yet, all those control measures failed to bring about full stock sanitation on industrialised units. Sow trading was not permitted until at least four weeks had elapsed from full effectiveness of mother animal vaccination, with the view to reducing the proliferation of Clostridium perfringens Type C via sales of breeding animals. All sows were given two \"Enterotox\u00e4mievakzine Dessau bivalent\" vaccinations, prior to sale. The animals were sold only to smaller farms (less than 500 sows for breeding) with concentional keeping patterns which were kept under constant diagnostic supervision. Neomycin, oxytetracycline, chloramphenicol, and other antibiotics against which Clostridium perfringens was resistant or in a position to assume resistance were used on endangered stocks only in conjunction with penicillin or not at all. This programme of control has proved to be efficient through a period of more than three years."}
{"id": "PMID:232842", "title": "[Studies of the regulation potential of glucose metabolism in the calf following infusion of fructose solution and using various hormones (ACTH, prednisolone, adrenaline and noradrenaline)].", "content": "Infusion of fructose solution (25 g in 100 ml) in sugar rations of 0.5 g or 1.0 g per kilogram of body weight usually induced in calf temporary drop of glucose in the blood plasma. This was attributable to rise in insulin secretion and glucose conversion or insufficiently fast effectiveness of insulin antagonists (adrenaline, glucagon, glucocorticosteroids). Such glucose drop could not be prevented by administration of 50 mg of prednisolone four hours before fructose infusion and 25 IU of ACTH five hours before infusion. Glucose as well as free fatty acids in the blood plasma went up in response to injection of 2.5 microgram/kg body weight during hypoglycaemia. The action of adrenaline was found to depend on the insulin dose given before in cases of insulin-induced hypoglycaemia. Doses of 0.5 g fructose per kilogram of body weight were administered in nine experimental infusions. Average half-life recorded from the blood plasma was 21.3 +/- 3.4 minutes.", "contents": "[Studies of the regulation potential of glucose metabolism in the calf following infusion of fructose solution and using various hormones (ACTH, prednisolone, adrenaline and noradrenaline)]. Infusion of fructose solution (25 g in 100 ml) in sugar rations of 0.5 g or 1.0 g per kilogram of body weight usually induced in calf temporary drop of glucose in the blood plasma. This was attributable to rise in insulin secretion and glucose conversion or insufficiently fast effectiveness of insulin antagonists (adrenaline, glucagon, glucocorticosteroids). Such glucose drop could not be prevented by administration of 50 mg of prednisolone four hours before fructose infusion and 25 IU of ACTH five hours before infusion. Glucose as well as free fatty acids in the blood plasma went up in response to injection of 2.5 microgram/kg body weight during hypoglycaemia. The action of adrenaline was found to depend on the insulin dose given before in cases of insulin-induced hypoglycaemia. Doses of 0.5 g fructose per kilogram of body weight were administered in nine experimental infusions. Average half-life recorded from the blood plasma was 21.3 +/- 3.4 minutes."}
{"id": "PMID:232843", "title": "Purification and characterization of bovine leukemia virus DNA polymerase.", "content": "An RNA-directed DNA polymerase was purified from bovine leukemia virus (BLV) by successive glycerol gradient centrifugation, column chromatography on phosphocellulose and gel filtration on Sephadex G-200. The purified DNA polymerase transcribes heteropolymeric regions of 30--40 S RNA isolated from avian myeloblastosis virus. The enzyme differs from other known DNA polymerases of mammalian type-C RNA tumor viruses by the following properties: 1. Its apparent molecular weight as estimated by velocity sedimentation data is 58,000 at 0.12 M KCl and 43,000 in the presence of 0.50 M KCl. 2. It has a Mg2+ optimum of 10 mM, and a Mn2+ optimum of 0.25 mM with (rA)n-(dT)10 as template. 3. At 50 mM KCl it is inhibited more than 70%, but it is not inhibited by phosphate ions at 2 mM. These properties confirm the peculiar position of BLV within the family Retraviridae.", "contents": "Purification and characterization of bovine leukemia virus DNA polymerase. An RNA-directed DNA polymerase was purified from bovine leukemia virus (BLV) by successive glycerol gradient centrifugation, column chromatography on phosphocellulose and gel filtration on Sephadex G-200. The purified DNA polymerase transcribes heteropolymeric regions of 30--40 S RNA isolated from avian myeloblastosis virus. The enzyme differs from other known DNA polymerases of mammalian type-C RNA tumor viruses by the following properties: 1. Its apparent molecular weight as estimated by velocity sedimentation data is 58,000 at 0.12 M KCl and 43,000 in the presence of 0.50 M KCl. 2. It has a Mg2+ optimum of 10 mM, and a Mn2+ optimum of 0.25 mM with (rA)n-(dT)10 as template. 3. At 50 mM KCl it is inhibited more than 70%, but it is not inhibited by phosphate ions at 2 mM. These properties confirm the peculiar position of BLV within the family Retraviridae."}
{"id": "PMID:232844", "title": "Metabolism of cyclic nucleotides in allergic rhinitis: studies on lymphocytes, granulocytes, and plasma level.", "content": "The effect of isoproterenol on the cyclic nucleotide level in peripheral lymphocytes and granulocytes with allergic rhinitis patients and normal subjects has been studied. Responsiveness to 10(-5) M isoproterenol of lymphocytes decreased in the case of allergic rhinitis patients. When asthma was complicated to perennial rhinitis, a more significant depression was noted. In granulocytes the same tendency as with lymphocytes was noted although the difference was not significant. Basal level and responsiveness to 5 X 10(-3) M theophylline of both lymphocytes and granulocytes were similar in allergic rhinitis patients to normal subjects. The ratio of plasma cAMP to cGMP concentration was lower in the allergic rhinitis patients although the difference was not significant.", "contents": "Metabolism of cyclic nucleotides in allergic rhinitis: studies on lymphocytes, granulocytes, and plasma level. The effect of isoproterenol on the cyclic nucleotide level in peripheral lymphocytes and granulocytes with allergic rhinitis patients and normal subjects has been studied. Responsiveness to 10(-5) M isoproterenol of lymphocytes decreased in the case of allergic rhinitis patients. When asthma was complicated to perennial rhinitis, a more significant depression was noted. In granulocytes the same tendency as with lymphocytes was noted although the difference was not significant. Basal level and responsiveness to 5 X 10(-3) M theophylline of both lymphocytes and granulocytes were similar in allergic rhinitis patients to normal subjects. The ratio of plasma cAMP to cGMP concentration was lower in the allergic rhinitis patients although the difference was not significant."}
{"id": "PMID:232847", "title": "[Behavior of serum 25-hydroxycholecalciferol in humans after administration of vitamin D and 25-OHD3].", "content": "Serum levels of 25 hydroxycholecalciferol were evaluated following i.m. and p.o. vit. D2 and D3 and p.o. 25OHD3 administration. While no increment in 25OHD3 serum levels were observed after i. m. administration of non-hydroxylated calciferols, a marked increment of the metabolite was found following the oral administration. However the peak values were largely impredictable. Acute and chronic p.o. administration of 25OHD3 determines a rapid and dose-dependent increase of the serum levels of the metabolite. In addition considering that a lower dosage is required of 25OHD3 compared to vit. D, this metabolite is preferable in the therapeutic use.", "contents": "[Behavior of serum 25-hydroxycholecalciferol in humans after administration of vitamin D and 25-OHD3]. Serum levels of 25 hydroxycholecalciferol were evaluated following i.m. and p.o. vit. D2 and D3 and p.o. 25OHD3 administration. While no increment in 25OHD3 serum levels were observed after i. m. administration of non-hydroxylated calciferols, a marked increment of the metabolite was found following the oral administration. However the peak values were largely impredictable. Acute and chronic p.o. administration of 25OHD3 determines a rapid and dose-dependent increase of the serum levels of the metabolite. In addition considering that a lower dosage is required of 25OHD3 compared to vit. D, this metabolite is preferable in the therapeutic use."}
{"id": "PMID:232848", "title": "Interference of MHV3 virus on ascites tumor growth.", "content": "In this experimental study the Authors have evaluated the interference of MHV3 hepatitis virus on Ascites Tumor's growth, using 4 groups of mice, the first one considered as control, the others inoculated with the virus 48 hours before, at the same time and 48 hours after tumor's inoculation. In each group labeling index, mitotic index and ascites volume were assessed a week after tumor's inoculation. The results seem to reveal an inhibition of tumor's growth in the second group. For this reason on the base of these encouraging observation, the Authors will continue researches to further confirm these preliminary results.", "contents": "Interference of MHV3 virus on ascites tumor growth. In this experimental study the Authors have evaluated the interference of MHV3 hepatitis virus on Ascites Tumor's growth, using 4 groups of mice, the first one considered as control, the others inoculated with the virus 48 hours before, at the same time and 48 hours after tumor's inoculation. In each group labeling index, mitotic index and ascites volume were assessed a week after tumor's inoculation. The results seem to reveal an inhibition of tumor's growth in the second group. For this reason on the base of these encouraging observation, the Authors will continue researches to further confirm these preliminary results."}
{"id": "PMID:232849", "title": "The development and significance of transaminases and 5(1)-nucleotidase (5(1)-ribonucleotide phosphohydrolase) in chick testis.", "content": "The development of testicular glutamate oxaloacetate (GOT) and glutamate pyruvate (GPT) transaminases and of 5'-Nucleotidase was monitored in the male Nigerian fowl. The findings indicated triphasic and monophasic oscillations of GOT and GPT respectively with age. 5(1)-Nucleotidase was found to decrease with increase in the chronological age of the chicks. Furthermore, while GOT and GPT exhibited cubic and quadratic relationships respectively with age and testicular weights, 5(1)-Nucleotidase was related to both variables in a quadratic manner. The results are discussed in terms of spermatogenesis which may bear profoundly on the overall reproductive performance traits of the Nigerian cockerel.", "contents": "The development and significance of transaminases and 5(1)-nucleotidase (5(1)-ribonucleotide phosphohydrolase) in chick testis. The development of testicular glutamate oxaloacetate (GOT) and glutamate pyruvate (GPT) transaminases and of 5'-Nucleotidase was monitored in the male Nigerian fowl. The findings indicated triphasic and monophasic oscillations of GOT and GPT respectively with age. 5(1)-Nucleotidase was found to decrease with increase in the chronological age of the chicks. Furthermore, while GOT and GPT exhibited cubic and quadratic relationships respectively with age and testicular weights, 5(1)-Nucleotidase was related to both variables in a quadratic manner. The results are discussed in terms of spermatogenesis which may bear profoundly on the overall reproductive performance traits of the Nigerian cockerel."}
{"id": "PMID:232851", "title": "Hepatitis, cardiomyopathy and hemodynamics in furazolidone-induced round heart disease of turkeys.", "content": "Twenty-five large broad-breasted white turkeys were fed a 22% protein diet supplemented with 500 ppm furazolidone from day 1 to 3.5 weeks of age and the same diet supplemented with 700 ppm furazolidone until 9.5 weeks of age. Following the development of round heart disease as indicated by altered electrocardiograms the 25 turkeys were sacrificed. In the livers of turkeys with biventricular dilatation (72% of cases) there was bile duct hyperlasia, portal fibrosis and intracytoplasmic globules in the hepatocytes. Globules stained pink with hematoxylin-eosin, deep red with PAS and variable with Massons trichrome stains in paraffin-embedded liver sections. Clear intracytoplasmic vacuoles demonstrable in hepatocytes of PAS stained liver sections embedded in paraffin did not stain as lipid in frozen sections but did contain sparse flocculent material in 1 micrometer sections of liver embedded in epoxy resin and stained with toluidine blue. At the subcellular level, the intracytoplasmic globules in hepatocytes were surrounded by a single membrane, contained flocculent material and had enzymatic properties characteristic of lysosomes. Blood pressure, heart rate, dp/dt max, total plasma proteins and plasma trypsin inhibitory capacity of turkeys with round heart disease were lower than corresponding values for control turkeys. Control turkeys did not exhibit the characteristic gross or microscopic lesions of round heart disease.", "contents": "Hepatitis, cardiomyopathy and hemodynamics in furazolidone-induced round heart disease of turkeys. Twenty-five large broad-breasted white turkeys were fed a 22% protein diet supplemented with 500 ppm furazolidone from day 1 to 3.5 weeks of age and the same diet supplemented with 700 ppm furazolidone until 9.5 weeks of age. Following the development of round heart disease as indicated by altered electrocardiograms the 25 turkeys were sacrificed. In the livers of turkeys with biventricular dilatation (72% of cases) there was bile duct hyperlasia, portal fibrosis and intracytoplasmic globules in the hepatocytes. Globules stained pink with hematoxylin-eosin, deep red with PAS and variable with Massons trichrome stains in paraffin-embedded liver sections. Clear intracytoplasmic vacuoles demonstrable in hepatocytes of PAS stained liver sections embedded in paraffin did not stain as lipid in frozen sections but did contain sparse flocculent material in 1 micrometer sections of liver embedded in epoxy resin and stained with toluidine blue. At the subcellular level, the intracytoplasmic globules in hepatocytes were surrounded by a single membrane, contained flocculent material and had enzymatic properties characteristic of lysosomes. Blood pressure, heart rate, dp/dt max, total plasma proteins and plasma trypsin inhibitory capacity of turkeys with round heart disease were lower than corresponding values for control turkeys. Control turkeys did not exhibit the characteristic gross or microscopic lesions of round heart disease."}
{"id": "PMID:232852", "title": "Dolphin pox: a skin disease of cetaceans.", "content": "Poxvirus has been identified morphologically from skin lesions in captive and free-ranging bottlenosed dolphins, Tursiops truncatus and a stranded Atlantic white-sided dolphin, Lagenorhynchus acutus. The lesions, commonly referred to as ring or pinhole lesions, appear as solitary or coalesced circular grey blemishes. Advanced ring lesions may take the form of black punctiform stippled patterns known as \"tattoo\". Histologically, the stratum externum is thickened, and there is ballooning degeneration and eosinophilic intractyoplasmic inclusions in the stratum intermedium. These includions contain virus particles which exhibit typical poxvirus morphology. Stress, environmental conditions and general health appear to play a major role in the clinical manifestation of dolphin pox.", "contents": "Dolphin pox: a skin disease of cetaceans. Poxvirus has been identified morphologically from skin lesions in captive and free-ranging bottlenosed dolphins, Tursiops truncatus and a stranded Atlantic white-sided dolphin, Lagenorhynchus acutus. The lesions, commonly referred to as ring or pinhole lesions, appear as solitary or coalesced circular grey blemishes. Advanced ring lesions may take the form of black punctiform stippled patterns known as \"tattoo\". Histologically, the stratum externum is thickened, and there is ballooning degeneration and eosinophilic intractyoplasmic inclusions in the stratum intermedium. These includions contain virus particles which exhibit typical poxvirus morphology. Stress, environmental conditions and general health appear to play a major role in the clinical manifestation of dolphin pox."}
{"id": "PMID:232853", "title": "Bovine fetal inoculations with calf rotavirus.", "content": "The serological and histopathological responses of bovine fetuses to in utero inoculation with virulent and attenuated strains of the calf rotavirus (reovirus-like agent of neonatal calf diarrhea) are described. Thirteen bovine fetuses, 63 to 190 days of gestation, were inoculated in utero with attenuated (three fetuses) or field strain virus (nine fetuses) or both (one fetus).Serum-neutralizing antibody titers ranging from 1:16 to > 1:256 were detected in six of eight fetuses tested, demonstrating the ability of the bovine fetus to respond immunologically to this agent. The youngest fetus in the series was inoculated at 63 days of gestation and developed a titer of 128 in 64 days. This represents the earliest stage of gestation at which a bovine fetus has been inoculated with a bovine virus and found to produce antibody to it. Serum neutralizing titers in six of the eight dams tested increased significantly following the inoculations of their fetuses in utero. Histological changes associated with viral replication and antigenic stimulation of the lymphoreticular system were observed. Pneumonic lesions consisting of both local and diffuse lymphoreticular proliferation were present in five of the nine fetuses that were alive at slaughter. Gliosis and perivascular cuffing were noted in the brains of two of these fetuses and meningitis was seen in one. No evidence of teratogenic change was found.", "contents": "Bovine fetal inoculations with calf rotavirus. The serological and histopathological responses of bovine fetuses to in utero inoculation with virulent and attenuated strains of the calf rotavirus (reovirus-like agent of neonatal calf diarrhea) are described. Thirteen bovine fetuses, 63 to 190 days of gestation, were inoculated in utero with attenuated (three fetuses) or field strain virus (nine fetuses) or both (one fetus).Serum-neutralizing antibody titers ranging from 1:16 to > 1:256 were detected in six of eight fetuses tested, demonstrating the ability of the bovine fetus to respond immunologically to this agent. The youngest fetus in the series was inoculated at 63 days of gestation and developed a titer of 128 in 64 days. This represents the earliest stage of gestation at which a bovine fetus has been inoculated with a bovine virus and found to produce antibody to it. Serum neutralizing titers in six of the eight dams tested increased significantly following the inoculations of their fetuses in utero. Histological changes associated with viral replication and antigenic stimulation of the lymphoreticular system were observed. Pneumonic lesions consisting of both local and diffuse lymphoreticular proliferation were present in five of the nine fetuses that were alive at slaughter. Gliosis and perivascular cuffing were noted in the brains of two of these fetuses and meningitis was seen in one. No evidence of teratogenic change was found."}
{"id": "PMID:232854", "title": "[Renal transplantation in the child. Medical and surgical aspects (author's transl)].", "content": "The authors report the experience of the Children's Hospital of Marseille about ten renal transplantations in nine children. Indications, immunosuppressive treatment, surgical techniques employed are detailed. The results study show two mains complications : rejection and arterial hypertension. A better recipient selection, as in adults, would increase good results.", "contents": "[Renal transplantation in the child. Medical and surgical aspects (author's transl)]. The authors report the experience of the Children's Hospital of Marseille about ten renal transplantations in nine children. Indications, immunosuppressive treatment, surgical techniques employed are detailed. The results study show two mains complications : rejection and arterial hypertension. A better recipient selection, as in adults, would increase good results."}
{"id": "PMID:232855", "title": "[Benign synovialoma of knee in children (author's transl)].", "content": "The authors report 2 cases of benign synovialoma of knee in children. After studying the clinical and radiological symptomatology, they insist on the anatomical pathological criteria which are the only specific ones. However, this benign affection takes on a serious complexion, in the diffuse forms, on account of the incomplete and impairing nature of an exclusively surgical treatment.", "contents": "[Benign synovialoma of knee in children (author's transl)]. The authors report 2 cases of benign synovialoma of knee in children. After studying the clinical and radiological symptomatology, they insist on the anatomical pathological criteria which are the only specific ones. However, this benign affection takes on a serious complexion, in the diffuse forms, on account of the incomplete and impairing nature of an exclusively surgical treatment."}
{"id": "PMID:232856", "title": "[Undifferentiated renal sarcoma or Wilm's tumor (author's transl)].", "content": "About a case in a six year old Negro boy, the existence of a special pattern among the malignant renal tumors in children is emphasized; this tumor is marked from the Wilms' tumor by its peculiar behaviour (frequently poor evolution, high incidence of osseous metastasis in contrast with the rate occurrence of pulmonary involvement) and by a sarcomatous appearance at the pathologic examination. The classification and the suitable therapeutic management are discussed.", "contents": "[Undifferentiated renal sarcoma or Wilm's tumor (author's transl)]. About a case in a six year old Negro boy, the existence of a special pattern among the malignant renal tumors in children is emphasized; this tumor is marked from the Wilms' tumor by its peculiar behaviour (frequently poor evolution, high incidence of osseous metastasis in contrast with the rate occurrence of pulmonary involvement) and by a sarcomatous appearance at the pathologic examination. The classification and the suitable therapeutic management are discussed."}
{"id": "PMID:232857", "title": "[Cyto-immunochemical detection of gamma endorphin in swine adenohypophysis].", "content": "An immunserum was prepared from gamma endorphin and its specifity was checked by the indirect method. It was tested on hypophysis which were taken from Pigs since birth till 3 months old. The anterior lobe as well as the intermediate lobe have reacted. The same cells were positive in the anterior lobe and recognized the anti-ACTH, anti-beta MSH and anti-beta LPH immunserums. However, the reaction was more labile than with these last immunserums and it was varying with the delay of fixation after the death and the penetration in the gland by the fixator.", "contents": "[Cyto-immunochemical detection of gamma endorphin in swine adenohypophysis]. An immunserum was prepared from gamma endorphin and its specifity was checked by the indirect method. It was tested on hypophysis which were taken from Pigs since birth till 3 months old. The anterior lobe as well as the intermediate lobe have reacted. The same cells were positive in the anterior lobe and recognized the anti-ACTH, anti-beta MSH and anti-beta LPH immunserums. However, the reaction was more labile than with these last immunserums and it was varying with the delay of fixation after the death and the penetration in the gland by the fixator."}
{"id": "PMID:232858", "title": "[Persistence of paradoxical sleep in the cat after destruction of the pontine gagantocellular tegmental field with kainic acid].", "content": "The pontine gigantocellular tegmental field (FTG) does not play any role in paradoxical sleep (PS) since the destruction of the cell bodies of the FTG with ka\u00efnic acid does not alter PS in the Cat. Elimination of PS following electrolytic destruction of the ventrolateral pontine reticular formation can be explained by lesions of fibers connecting the region of the locus caeruleus and the bulbar reticular formation.", "contents": "[Persistence of paradoxical sleep in the cat after destruction of the pontine gagantocellular tegmental field with kainic acid]. The pontine gigantocellular tegmental field (FTG) does not play any role in paradoxical sleep (PS) since the destruction of the cell bodies of the FTG with ka\u00efnic acid does not alter PS in the Cat. Elimination of PS following electrolytic destruction of the ventrolateral pontine reticular formation can be explained by lesions of fibers connecting the region of the locus caeruleus and the bulbar reticular formation."}
{"id": "PMID:232859", "title": "[Fragments of linear unintegrated Rous sarcoma virus DNA, resulting from digestion with SmaI restriction endonuclease].", "content": "Linear unintegrated DNA of Schmidt-Ruppin Rous sarcoma virus, subgroup D (SR-RSV-D), was digested with SmaI restriction endonuclease, analyzed by agarose gel electrophoresis, \"blotted\" by Southern's method and hybridized with a viral 32P cDNA. SmaI cleaves this DNA at five sites, two of which are localized at the ends of the provirus. Src and env genes seem not to be restrictied by SmaI cleavage.", "contents": "[Fragments of linear unintegrated Rous sarcoma virus DNA, resulting from digestion with SmaI restriction endonuclease]. Linear unintegrated DNA of Schmidt-Ruppin Rous sarcoma virus, subgroup D (SR-RSV-D), was digested with SmaI restriction endonuclease, analyzed by agarose gel electrophoresis, \"blotted\" by Southern's method and hybridized with a viral 32P cDNA. SmaI cleaves this DNA at five sites, two of which are localized at the ends of the provirus. Src and env genes seem not to be restrictied by SmaI cleavage."}
{"id": "PMID:232860", "title": "[Purification of a membrane protein modifying the sensitivity of Na+/K+ ATPase to ouabain from a supernatant of plasma membrane treated with EDTA].", "content": "A membrane protein of M. W. 32,000 D and pI 5 has been purified from EDTA-treated plasma membrane supernatants by Page without detergents. These membranes are purified from the MF2S cell line issued from the murine plasmacytoma MOPC 173. The purified protein was able to induce a 300 fold increase in the Na+/K+ ATPase resistance to ouaba\u00efn thus mimicking the original resistance of the enzyme to the drug.", "contents": "[Purification of a membrane protein modifying the sensitivity of Na+/K+ ATPase to ouabain from a supernatant of plasma membrane treated with EDTA]. A membrane protein of M. W. 32,000 D and pI 5 has been purified from EDTA-treated plasma membrane supernatants by Page without detergents. These membranes are purified from the MF2S cell line issued from the murine plasmacytoma MOPC 173. The purified protein was able to induce a 300 fold increase in the Na+/K+ ATPase resistance to ouaba\u00efn thus mimicking the original resistance of the enzyme to the drug."}
{"id": "PMID:232861", "title": "[Purification from a total cellular lysate of a protein modifying the sensitivity of Na+/K+ ATPase to ouabain].", "content": "A protein (32,000 dalton) has been purified from M2FS cells derived from the murine plasmocytoma MOPC 173. Like tropomyosin, this protein when added with Ca++ to EDTA-treated plasma membranes prepared from the same cell, induced a drastic increase in the Na+/K+ atpase resistance to ouabain.", "contents": "[Purification from a total cellular lysate of a protein modifying the sensitivity of Na+/K+ ATPase to ouabain]. A protein (32,000 dalton) has been purified from M2FS cells derived from the murine plasmocytoma MOPC 173. Like tropomyosin, this protein when added with Ca++ to EDTA-treated plasma membranes prepared from the same cell, induced a drastic increase in the Na+/K+ atpase resistance to ouabain."}
{"id": "PMID:232872", "title": "[Glucagon-producing endocrine pancreas tumors. Symptoms, diagnosis, localization, therapy and follow-up].", "content": "Three cases of glucagonoma syndrome caused by glucagon producing pancreatic islet cell tumors are reported. Modern procedures for diagnosis, localization, and classification are presented and advocated.", "contents": "[Glucagon-producing endocrine pancreas tumors. Symptoms, diagnosis, localization, therapy and follow-up]. Three cases of glucagonoma syndrome caused by glucagon producing pancreatic islet cell tumors are reported. Modern procedures for diagnosis, localization, and classification are presented and advocated."}
{"id": "PMID:232874", "title": "Impaired immune function and identification of polybrominated biphenyls (PBB) in blood compartments of exposed Michigan dairy farmers and chemical workers.", "content": "In 1973 PBB's were accidentally mixed into animal feed, resulting in marked toxic effects. Meat and dairy products were widely consumed in Michigan. To determine the impact of PBB's, 55 exposed Michigan farm residents, 11 Michigan chemical workers and 46 non-exposed Wisconsin farmers were examined. Abnormalities included decreased number of T-lymphocytes with concomitant increase of lymphocytes with no detectable surface markers, \"null cells\", and altered lymphocyte function. Data obtained from skin testing using standard recall antigens, showed no consistent correlation between the delayed cutaneous hypersensitivity response and the impaired lymphocyte function. PBB (hexa) in separated white blood cells and red cells was positively identified and quantified by gas chromatography-mass spectrometry. PBB and immunological abnormalities were not detected in non-exposed Wisconsin dairy farm residents.", "contents": "Impaired immune function and identification of polybrominated biphenyls (PBB) in blood compartments of exposed Michigan dairy farmers and chemical workers. In 1973 PBB's were accidentally mixed into animal feed, resulting in marked toxic effects. Meat and dairy products were widely consumed in Michigan. To determine the impact of PBB's, 55 exposed Michigan farm residents, 11 Michigan chemical workers and 46 non-exposed Wisconsin farmers were examined. Abnormalities included decreased number of T-lymphocytes with concomitant increase of lymphocytes with no detectable surface markers, \"null cells\", and altered lymphocyte function. Data obtained from skin testing using standard recall antigens, showed no consistent correlation between the delayed cutaneous hypersensitivity response and the impaired lymphocyte function. PBB (hexa) in separated white blood cells and red cells was positively identified and quantified by gas chromatography-mass spectrometry. PBB and immunological abnormalities were not detected in non-exposed Wisconsin dairy farm residents."}
{"id": "PMID:232873", "title": "The emotion of pain and its chemistry.", "content": "Pain is not an electrical impulse derived from tissue injury but an emotional experience arising when a nervous input is interpreted in the light of experience and emotional context as being 'painful'. Pain may thus signify tissue damage, vivid sensory experience or inner turmoil. Pain may be distressing but it can also be pleasurable. Whether a given stimulus provokes pain and whether that emotional feeling causes distress varies from individual to individual and from moment to moment. The brain possesses chemically mediated mechanisms that can exert control over the experience of 'pain'. An understanding of such mechanisms suggests new approaches to the relief of distressing pain (and to the artificial production of pleasurable pain).", "contents": "The emotion of pain and its chemistry. Pain is not an electrical impulse derived from tissue injury but an emotional experience arising when a nervous input is interpreted in the light of experience and emotional context as being 'painful'. Pain may thus signify tissue damage, vivid sensory experience or inner turmoil. Pain may be distressing but it can also be pleasurable. Whether a given stimulus provokes pain and whether that emotional feeling causes distress varies from individual to individual and from moment to moment. The brain possesses chemically mediated mechanisms that can exert control over the experience of 'pain'. An understanding of such mechanisms suggests new approaches to the relief of distressing pain (and to the artificial production of pleasurable pain)."}
{"id": "PMID:232875", "title": "[Dopa and dopamine agonists in depression (author's transl)].", "content": "Following a summary of the functional organisation of the ascending dopamine systems, the pharmacology of the dopamine synaptic receptors is considered. The stress is placed upon the differences induced by dopamine agonists during short-term and long-term treatment. In this connection, recent ideas on the heterogeneous nature of the dopamine receptors, on their specificity and on their functional role will be discussed. The dopaminergic action of certain antidepressants will be studied by analysing the different types of activity: presynaptic release, direct pre- or post-synaptic agonism. The role of dopaminergic transmission in depression of mood is considered finally on the basis of clinico-biochemical correlations. Finally, dopaminergic activity is linked with the other possible changes in cerebral monoamines by drafting a table of the interactions between the neurotransmitters.", "contents": "[Dopa and dopamine agonists in depression (author's transl)]. Following a summary of the functional organisation of the ascending dopamine systems, the pharmacology of the dopamine synaptic receptors is considered. The stress is placed upon the differences induced by dopamine agonists during short-term and long-term treatment. In this connection, recent ideas on the heterogeneous nature of the dopamine receptors, on their specificity and on their functional role will be discussed. The dopaminergic action of certain antidepressants will be studied by analysing the different types of activity: presynaptic release, direct pre- or post-synaptic agonism. The role of dopaminergic transmission in depression of mood is considered finally on the basis of clinico-biochemical correlations. Finally, dopaminergic activity is linked with the other possible changes in cerebral monoamines by drafting a table of the interactions between the neurotransmitters."}
{"id": "PMID:232878", "title": "Relative rates at which dominant-lethal mutations and heritable translocations are induced by alkylating chemicals in postmeiotic male germ cells of mice.", "content": "There is a close relationship between the rates at which dominant lethal mutations and heritable translocations are induced by ethyl methanesulfonate (EMS) or triethylenemelamine (TEM) in male postmeiotic germ cells. This relationship does not hold for isopropyl methanesulfonate (IMS), which induced only negligible frequencies of heritable translocations at doses that induced high levels of dominant lethal mutations. Nor does IMS behave like EMS and TEM in the degree to which eggs of different stocks of females repair premutational lesions that are carried in the sperm-large differences between stocks for IMS treatment and small differences for EMS or TEM treatment. These dissimilarities between IMS and the other two alkylating chemicals are postulated to be attributable to differences in the types of lesions present at the time of repair activity and to whether or not chromosomal aberrations are already fixed prior to postfertilization pronuclear DNA synthesis.", "contents": "Relative rates at which dominant-lethal mutations and heritable translocations are induced by alkylating chemicals in postmeiotic male germ cells of mice. There is a close relationship between the rates at which dominant lethal mutations and heritable translocations are induced by ethyl methanesulfonate (EMS) or triethylenemelamine (TEM) in male postmeiotic germ cells. This relationship does not hold for isopropyl methanesulfonate (IMS), which induced only negligible frequencies of heritable translocations at doses that induced high levels of dominant lethal mutations. Nor does IMS behave like EMS and TEM in the degree to which eggs of different stocks of females repair premutational lesions that are carried in the sperm-large differences between stocks for IMS treatment and small differences for EMS or TEM treatment. These dissimilarities between IMS and the other two alkylating chemicals are postulated to be attributable to differences in the types of lesions present at the time of repair activity and to whether or not chromosomal aberrations are already fixed prior to postfertilization pronuclear DNA synthesis."}
{"id": "PMID:232884", "title": "Separation of some polypeptide hormones by high-performance liquid chromatography.", "content": "Twenty-one analogues of ACTH, three analogues of LH-RH and four insulins have been successfully separated on a commercial reversed-phase material with tartrate buffer--acetonitrile systems containing sodium 1-butanesulphonate and sodium sulphate as the mobile phase. The effect of the constituent amino acid residues on the order of elution has been studied in detail by using a variety of closely related peptides; the order of elution of a series of peptides, which differ by only one amino acid residue, can in most instances be explained in terms of the difference in the hydrophobicities of the amino acid residues concerned, but in some instances, such as in diastereoisomers or positional isomers, the order of elution must be interpreted in terms of the hydrophobicity of the whole peptide molecule. This chromatographic method has been proved to be very useful for the rapid examination of the purity of these peptide hormones and for the separation of closely related peptides with molecular weights up to ca. 6000.", "contents": "Separation of some polypeptide hormones by high-performance liquid chromatography. Twenty-one analogues of ACTH, three analogues of LH-RH and four insulins have been successfully separated on a commercial reversed-phase material with tartrate buffer--acetonitrile systems containing sodium 1-butanesulphonate and sodium sulphate as the mobile phase. The effect of the constituent amino acid residues on the order of elution has been studied in detail by using a variety of closely related peptides; the order of elution of a series of peptides, which differ by only one amino acid residue, can in most instances be explained in terms of the difference in the hydrophobicities of the amino acid residues concerned, but in some instances, such as in diastereoisomers or positional isomers, the order of elution must be interpreted in terms of the hydrophobicity of the whole peptide molecule. This chromatographic method has been proved to be very useful for the rapid examination of the purity of these peptide hormones and for the separation of closely related peptides with molecular weights up to ca. 6000."}
{"id": "PMID:232885", "title": "Spectrodensitometric determination of trichothecene mycotoxins with 4-(p-nitrobenzyl)pyridine on silica gel thin-layer chromatograms.", "content": "A simple method for the detection and spectrodensitometric determination of a number of trichothecene mycotoxins on silica gel layers based on a colour reaction between 4-(p-nitrobenzyl)pyridine and the 12,13-epoxy group in the trichothecene nucleus is described. The detection limits for the twelve trichothecenes examined were 0.025--0.2 micrograms per spot. Further, six of the twelve trichothecenes could be determined spectrodensitometrically in the range from ca. 0.05--0.2 to 10 micrograms per spot with a coefficient of variation of ca. 5%.", "contents": "Spectrodensitometric determination of trichothecene mycotoxins with 4-(p-nitrobenzyl)pyridine on silica gel thin-layer chromatograms. A simple method for the detection and spectrodensitometric determination of a number of trichothecene mycotoxins on silica gel layers based on a colour reaction between 4-(p-nitrobenzyl)pyridine and the 12,13-epoxy group in the trichothecene nucleus is described. The detection limits for the twelve trichothecenes examined were 0.025--0.2 micrograms per spot. Further, six of the twelve trichothecenes could be determined spectrodensitometrically in the range from ca. 0.05--0.2 to 10 micrograms per spot with a coefficient of variation of ca. 5%."}
{"id": "PMID:232889", "title": "Effect of vasopressin and serosal hypertonicity on toad urinary bladder.", "content": "The mucosal surface of toad urinary bladder was examined with scanning electron microscopy following its exposure to 20 mU/ml of vasopressin (VP), 10(-4) M 8-bromo-cAMP, 1 mM acetylcholine chloride, serosal hypertonicity, or a hypotonic bathing medium. After a 30-min exposure to VP, the arborizing ridge-like surface pattern typical of granular cells was transformed into microvilli, a response that was not dependent on transepithelial osmotic water movement. An identical response occurred following a 30-min exposure of the bladder to 8-bromo-cAMP, again in the absence of an osmotic gradient. Microvillus formation was not observed when cell volume was increased by incubation of tissue in half-normal amphibian Ringer's solution for 30 min, or with exposure to acetylcholine, which caused accentuation of the convexity of the apical surface of the granular cell similar to that observed with VP-induced osmotic water flow. However, 60 min of incubation in a hypertonic serosal medium (mannitol, 240 mM) caused transformation of ridges to microvilli mimicking the picture obtained with VP. These findings establish that transepithelial osmotic water flow with cell swelling is not required for microvillus formation on the apical surface of granular cells following VP stimulation, and that the surface changes are not due to cell swelling alone or to changes in the configuration of the apical plasmalemma. The results also suggest that the response to VP is mediated via the generation of cAMP. Finally, this study demonstrates that serosal hypertonicity also causes transformation of ridges to microvilli by a mechanism that is yet to be defined.", "contents": "Effect of vasopressin and serosal hypertonicity on toad urinary bladder. The mucosal surface of toad urinary bladder was examined with scanning electron microscopy following its exposure to 20 mU/ml of vasopressin (VP), 10(-4) M 8-bromo-cAMP, 1 mM acetylcholine chloride, serosal hypertonicity, or a hypotonic bathing medium. After a 30-min exposure to VP, the arborizing ridge-like surface pattern typical of granular cells was transformed into microvilli, a response that was not dependent on transepithelial osmotic water movement. An identical response occurred following a 30-min exposure of the bladder to 8-bromo-cAMP, again in the absence of an osmotic gradient. Microvillus formation was not observed when cell volume was increased by incubation of tissue in half-normal amphibian Ringer's solution for 30 min, or with exposure to acetylcholine, which caused accentuation of the convexity of the apical surface of the granular cell similar to that observed with VP-induced osmotic water flow. However, 60 min of incubation in a hypertonic serosal medium (mannitol, 240 mM) caused transformation of ridges to microvilli mimicking the picture obtained with VP. These findings establish that transepithelial osmotic water flow with cell swelling is not required for microvillus formation on the apical surface of granular cells following VP stimulation, and that the surface changes are not due to cell swelling alone or to changes in the configuration of the apical plasmalemma. The results also suggest that the response to VP is mediated via the generation of cAMP. Finally, this study demonstrates that serosal hypertonicity also causes transformation of ridges to microvilli by a mechanism that is yet to be defined."}
{"id": "PMID:232891", "title": "Growth of kidney epithelial cells in hormone-supplemented, serum-free medium.", "content": "Madin Darby canine kidney cells can grow in synthetic medium supplemented with 5 factors--insulin, transferrin, prostaglandin E1, hydrocortisone and triiodothyronine--as a serum substitute. These 5 factors permit growth for one month in the absence of serum, and a growth rate equivalent to that observed in serum-supplemented medium. Dibutyryl cAMP substitutes for prostaglandin E1 in the medium, suggesting that increased growth of Maden Darby canine kidney cells results from increased intracellular cAMP. Potential applications of the serum-free medium are discussed. The medium permits the selective growth of primary epithelial cell cultures in teh absence of fibroblast overgrowth, and a defined analysis of the mechanisms by which hormones regulate hemicyst formation.", "contents": "Growth of kidney epithelial cells in hormone-supplemented, serum-free medium. Madin Darby canine kidney cells can grow in synthetic medium supplemented with 5 factors--insulin, transferrin, prostaglandin E1, hydrocortisone and triiodothyronine--as a serum substitute. These 5 factors permit growth for one month in the absence of serum, and a growth rate equivalent to that observed in serum-supplemented medium. Dibutyryl cAMP substitutes for prostaglandin E1 in the medium, suggesting that increased growth of Maden Darby canine kidney cells results from increased intracellular cAMP. Potential applications of the serum-free medium are discussed. The medium permits the selective growth of primary epithelial cell cultures in teh absence of fibroblast overgrowth, and a defined analysis of the mechanisms by which hormones regulate hemicyst formation."}
{"id": "PMID:232892", "title": "Isolation and characterization of a variant of B16-mouse melanoma resistant to MSH growth inhibition.", "content": "A variant of B-16 F1 mouse melanoma was selected for its ability to survive and replicate in the presence of melanocyte-stimulating hormone (MSH). Although the variant (MR-4) was completely resistant to growth inhibition of MSH, cyclic AMP was still able to block cell replication. Tyrosinase activity in MR-4 cells was considerably lower than in B-16 F1 cells. MSH induced a two fold to three-fold increase in tyrosinase activity in both cell types, but the absolute activity in MR-4 remained significantly less than in the parental cells. MR-4 cells were also found to have a markedly depressed cyclic AMP-dependent protein kinase activity relative to B-16 F1 cells. The protein kinase from both cell types was stimulated by cyclic AMP, but the level of MR-4 kinase activity at maximal cyclic AMP concentrations remained considerably lower than B-16 F1 kinase activity under the same conditions. In both cell types adenylate cyclase activity was markedly stimulated by MSH. When equal numbers of viable F1 and MR-4 cells were injected subcutaneously into C57/B1 mice, the MR-4 cells formed tumors earlier and killed the host sooner than the parental F1 cells. We conclude that the biochemical alteration which allows MR-4 cells to replicate in the presence of MSH is a low level of tyrosinase activity, which in turn may be the result of low cyclic AMP-dependent protein kinase activity.", "contents": "Isolation and characterization of a variant of B16-mouse melanoma resistant to MSH growth inhibition. A variant of B-16 F1 mouse melanoma was selected for its ability to survive and replicate in the presence of melanocyte-stimulating hormone (MSH). Although the variant (MR-4) was completely resistant to growth inhibition of MSH, cyclic AMP was still able to block cell replication. Tyrosinase activity in MR-4 cells was considerably lower than in B-16 F1 cells. MSH induced a two fold to three-fold increase in tyrosinase activity in both cell types, but the absolute activity in MR-4 remained significantly less than in the parental cells. MR-4 cells were also found to have a markedly depressed cyclic AMP-dependent protein kinase activity relative to B-16 F1 cells. The protein kinase from both cell types was stimulated by cyclic AMP, but the level of MR-4 kinase activity at maximal cyclic AMP concentrations remained considerably lower than B-16 F1 kinase activity under the same conditions. In both cell types adenylate cyclase activity was markedly stimulated by MSH. When equal numbers of viable F1 and MR-4 cells were injected subcutaneously into C57/B1 mice, the MR-4 cells formed tumors earlier and killed the host sooner than the parental F1 cells. We conclude that the biochemical alteration which allows MR-4 cells to replicate in the presence of MSH is a low level of tyrosinase activity, which in turn may be the result of low cyclic AMP-dependent protein kinase activity."}
{"id": "PMID:232899", "title": "Cellular basis of prolactin action: involvement of cyclic nucleotides, polyamines, prostaglandins, steroids, thyroid hormones, Na/K ATPases and calcium: relevance to breast cancer and the menstrual cycle.", "content": "The mechanisms of prolactin action are uncertain. Prolactin effects are characterised by great variability in the prolactin concentration required to produce a response and by the frequent occurrence of \"bell-shaped\" dose response curves. Relationships between prolactin and thyroid hormones and steroids are difficult to understand: both steroids and thyroid hormones may potentiate or inhibit prolactin effects in different situations. At the second messenger level, claims have been made that cyclic nucleotides, polyamines, Na/K ATPases and prostaglandins are involved. There is evidence that prostaglandin E1 may be an important second messenger and it is proposed that this is the clue to understanding the complexity. At low concentrations PGE1 enhances intracellular calcium release and at high concentrations PGE1 inhibits calcium release. The other second messengers proposed are all probably dependent upon calcium. Many prolactin effects may involve both PGE1 and another second messenger: at low prolactin concentrations PGE1 will potentiate the other messenger whereas at high concentrations the PGE1 effect will be inhibitory leading to a bell-shaped response. Thryoid hormones seem to enhance while glucocorticoids inhibit PGE1 synthesis. PGE1 dependent effects will thus be enhanced by thyroid hormone and blocked by cortisol. The reverse will be true of effects dependent on other second messengers.", "contents": "Cellular basis of prolactin action: involvement of cyclic nucleotides, polyamines, prostaglandins, steroids, thyroid hormones, Na/K ATPases and calcium: relevance to breast cancer and the menstrual cycle. The mechanisms of prolactin action are uncertain. Prolactin effects are characterised by great variability in the prolactin concentration required to produce a response and by the frequent occurrence of \"bell-shaped\" dose response curves. Relationships between prolactin and thyroid hormones and steroids are difficult to understand: both steroids and thyroid hormones may potentiate or inhibit prolactin effects in different situations. At the second messenger level, claims have been made that cyclic nucleotides, polyamines, Na/K ATPases and prostaglandins are involved. There is evidence that prostaglandin E1 may be an important second messenger and it is proposed that this is the clue to understanding the complexity. At low concentrations PGE1 enhances intracellular calcium release and at high concentrations PGE1 inhibits calcium release. The other second messengers proposed are all probably dependent upon calcium. Many prolactin effects may involve both PGE1 and another second messenger: at low prolactin concentrations PGE1 will potentiate the other messenger whereas at high concentrations the PGE1 effect will be inhibitory leading to a bell-shaped response. Thryoid hormones seem to enhance while glucocorticoids inhibit PGE1 synthesis. PGE1 dependent effects will thus be enhanced by thyroid hormone and blocked by cortisol. The reverse will be true of effects dependent on other second messengers."}
{"id": "PMID:232912", "title": "A family with massive acute vitamin D intoxication.", "content": "Acute massive vitamin D overdosage occurred in a family after eating food cooked in a nut oil containing 5 million units of vitamin D3/ml. The plasma vitamin D was 55 and 60 i.u./ml in the father and mother respectively, and 9.6 i.u./ml in their 11-month-old infant (normal range, 0--1.6 i.u/ml). All the family presented with symptoms of hypercalcaemia and the infant responded quickly to prednisone. After steroids had failed to control the hypercalcaemia in the parents, neutral phosphate was successful, although necessary for 9 months. Before phosphate therapy it was shown that both parents were in strongly negative calcium balance, indicating that the vitamin D was mobilizing calcium from bone. Eleven years later all 3 patients are well but a renal biopsy in one of them shows persistent nephrocalcinosis.", "contents": "A family with massive acute vitamin D intoxication. Acute massive vitamin D overdosage occurred in a family after eating food cooked in a nut oil containing 5 million units of vitamin D3/ml. The plasma vitamin D was 55 and 60 i.u./ml in the father and mother respectively, and 9.6 i.u./ml in their 11-month-old infant (normal range, 0--1.6 i.u/ml). All the family presented with symptoms of hypercalcaemia and the infant responded quickly to prednisone. After steroids had failed to control the hypercalcaemia in the parents, neutral phosphate was successful, although necessary for 9 months. Before phosphate therapy it was shown that both parents were in strongly negative calcium balance, indicating that the vitamin D was mobilizing calcium from bone. Eleven years later all 3 patients are well but a renal biopsy in one of them shows persistent nephrocalcinosis."}
{"id": "PMID:232914", "title": "Treatment of moderate to severe hypertensive patients with an orally active converting-enzyme inhibitor.", "content": "Seventeen hypertensive patients were treated with captopril, an orally active inhibitor of converting-enzyme. All patients showed a fall in blood pressure (BP), although in some patients only after the addition of diuretics. In 2 patients a skin rash developed. One patient developed proteinuria. A renal biopsy revealed membranous glomerulopathy. Correlations were found between pretreatment plasma renin activity (PRA) and the decrease in BP, and between pretreatment PRA and the decrease in plasma aldosterone concentration (PAC). Filtration fraction (FF) fell, indicating a decrease in renal vascular resistance. Captopril decreased the sensitivity to exogenous angiotensin I (AI), dependent on the captopril dose used. The sensitivity to exogenous bradykinin increased impressively even on the lowest dose of the drug. These observations suggest extrapulmonary conversion of AI to angiotensin II (AII).", "contents": "Treatment of moderate to severe hypertensive patients with an orally active converting-enzyme inhibitor. Seventeen hypertensive patients were treated with captopril, an orally active inhibitor of converting-enzyme. All patients showed a fall in blood pressure (BP), although in some patients only after the addition of diuretics. In 2 patients a skin rash developed. One patient developed proteinuria. A renal biopsy revealed membranous glomerulopathy. Correlations were found between pretreatment plasma renin activity (PRA) and the decrease in BP, and between pretreatment PRA and the decrease in plasma aldosterone concentration (PAC). Filtration fraction (FF) fell, indicating a decrease in renal vascular resistance. Captopril decreased the sensitivity to exogenous angiotensin I (AI), dependent on the captopril dose used. The sensitivity to exogenous bradykinin increased impressively even on the lowest dose of the drug. These observations suggest extrapulmonary conversion of AI to angiotensin II (AII)."}
{"id": "PMID:232915", "title": "Captopril and salt subtraction to treat \"uncontrollable\" hypertension in haemodialysis patients.", "content": "Eight patients on chronic haemodialysis for six months to 7 years with hypertension resistant to ultrafiltration and antihypertensive therapy, received Captopril (SQ 14, 225) an orally active inhibitor of converting enzyme. With this therapy, blood pressure was controlled in the 4 patients with the highest plasma renin activity. In the other 4, this treatment had to be supplemented with \"isovolumetric salt subtraction\", i.e. following conventional dialysis, 1-2 litres of ultrafiltrate were replaced by an equal volume of 5% glucose. The slight hyponatraemia induced by this procedure (plasma sodium 128mmol/L) was well tolerated. This procedure allows the removal of an excess of body sodium and seems to be effective even when conventional ultrafiltration during dialysis has failed. Administration of Captopril either alone or combined with \"isovolumetric salt subtraction\" induced good control of blood pressure in all 8 patients.", "contents": "Captopril and salt subtraction to treat \"uncontrollable\" hypertension in haemodialysis patients. Eight patients on chronic haemodialysis for six months to 7 years with hypertension resistant to ultrafiltration and antihypertensive therapy, received Captopril (SQ 14, 225) an orally active inhibitor of converting enzyme. With this therapy, blood pressure was controlled in the 4 patients with the highest plasma renin activity. In the other 4, this treatment had to be supplemented with \"isovolumetric salt subtraction\", i.e. following conventional dialysis, 1-2 litres of ultrafiltrate were replaced by an equal volume of 5% glucose. The slight hyponatraemia induced by this procedure (plasma sodium 128mmol/L) was well tolerated. This procedure allows the removal of an excess of body sodium and seems to be effective even when conventional ultrafiltration during dialysis has failed. Administration of Captopril either alone or combined with \"isovolumetric salt subtraction\" induced good control of blood pressure in all 8 patients."}
{"id": "PMID:232916", "title": "Renal osteopenia - an assessment of long-term therapy with vitamin D analogues.", "content": "Renal bone disease was assessed for an average of 5.5 years in 9 patients on maintenance haemodialysis. The investigative methods included serial biochemical estimations, radiographic skeletal surveys and quantitative bone histology. Repeated bone mineral analyses and neutron activation analyses of a hand were also performed in order to monitor changes in skeletal calcium content. Before treatment, progressive osteodystrophy was demonstrated by all techniques. Following therapy with the vitamin D analogues, all patients noted symptomatic improvement; serum alkaline phosphatase reverted to normal and serum parathyroid hormone concentrations decreased. Radiographically, subperiosteal erosions healed while the histological features of osteomalacia and osteitis fibrosa were abolished. Both bone mineral and neutron activation analyses indicated that progressive skeletal demineralisation had been halted. However, a sustained increase in the overall mineral content of bone was not demonstrated. Thus, vitamin D therapy although improving the biochemical, radiological, and histological features of renal osteodystrophy may not restore bone mass to osteopenic bone.", "contents": "Renal osteopenia - an assessment of long-term therapy with vitamin D analogues. Renal bone disease was assessed for an average of 5.5 years in 9 patients on maintenance haemodialysis. The investigative methods included serial biochemical estimations, radiographic skeletal surveys and quantitative bone histology. Repeated bone mineral analyses and neutron activation analyses of a hand were also performed in order to monitor changes in skeletal calcium content. Before treatment, progressive osteodystrophy was demonstrated by all techniques. Following therapy with the vitamin D analogues, all patients noted symptomatic improvement; serum alkaline phosphatase reverted to normal and serum parathyroid hormone concentrations decreased. Radiographically, subperiosteal erosions healed while the histological features of osteomalacia and osteitis fibrosa were abolished. Both bone mineral and neutron activation analyses indicated that progressive skeletal demineralisation had been halted. However, a sustained increase in the overall mineral content of bone was not demonstrated. Thus, vitamin D therapy although improving the biochemical, radiological, and histological features of renal osteodystrophy may not restore bone mass to osteopenic bone."}
{"id": "PMID:232917", "title": "Renal bone disorders in children: therapy with vitamin D3 or 1,25-dihydroxycholecalciferol.", "content": "Twelve children with chronic renal failure (CRF) and sixteen children receiving regular dialysis therapy (RDT) were treated with between 10,000 and 50,000 IU of vitamin D daily. This was associated with an increase in serum calcium levels and reduction in PTH levels. In the children with CRF, secondary hyperparathyroidism was improved with treatment but its development was not completely prevented nor was healing complete. In the patients receiving RDT, treatment with vitamin D improved the changes associated with secondary hyperparathyroidism in 50% of cases but these features sometimes reappeared despite continuing treatment. Hypercalcaemia or metastatic calcification was not seen. Subsequently, 1,25(OH)2D3 was administered to 14 children receiving RDT. This was associated with the return of serum calcium levels to normal, inhibition of PTH synthesis and an improvement in intestinal calcium absorption. Fibro-osteoclasia was cured and there was improvement in actual bone resorption. There was also improvement in osteoidosis in those children who showed disturbances of mineralisation. Calcification in the limbus area of the eyes may occur and hypercalcaemia was seen commonly. Treatment with 1,25(OH)2D3 should only be offered to children with severe renal bone disease. Neither vitamin D3 nor 1,25(OH)2D3 can guarantee complete recovery of osteodystrophy and of growth arrest in uraemic children.", "contents": "Renal bone disorders in children: therapy with vitamin D3 or 1,25-dihydroxycholecalciferol. Twelve children with chronic renal failure (CRF) and sixteen children receiving regular dialysis therapy (RDT) were treated with between 10,000 and 50,000 IU of vitamin D daily. This was associated with an increase in serum calcium levels and reduction in PTH levels. In the children with CRF, secondary hyperparathyroidism was improved with treatment but its development was not completely prevented nor was healing complete. In the patients receiving RDT, treatment with vitamin D improved the changes associated with secondary hyperparathyroidism in 50% of cases but these features sometimes reappeared despite continuing treatment. Hypercalcaemia or metastatic calcification was not seen. Subsequently, 1,25(OH)2D3 was administered to 14 children receiving RDT. This was associated with the return of serum calcium levels to normal, inhibition of PTH synthesis and an improvement in intestinal calcium absorption. Fibro-osteoclasia was cured and there was improvement in actual bone resorption. There was also improvement in osteoidosis in those children who showed disturbances of mineralisation. Calcification in the limbus area of the eyes may occur and hypercalcaemia was seen commonly. Treatment with 1,25(OH)2D3 should only be offered to children with severe renal bone disease. Neither vitamin D3 nor 1,25(OH)2D3 can guarantee complete recovery of osteodystrophy and of growth arrest in uraemic children."}
{"id": "PMID:232921", "title": "Circadian rhythm of cyclic nucleotide and GABA levels in the rat brain.", "content": "Daily variation in the levels of cyclic nucleotides and GABA was examined in seven brain regions of male Sprague-Dawley rats. Significant daily rhythm of cyclic AMP levels was found in the cerebellum and pons medulla oblongata. Circadian variation of cyclic GMP levels was found in the cerebellum, cerebral cortex, striatum, and hypothalamus. Daily variation of GABA levels was found in the pons medulla oblongata and striatum. Cyclic GMP in the pons medulla oblongata and GABA in the hypothalamus were found to exhibit ultradian variation of levels. These observed daily fluctuations of baseline levels should be considered when examining the duration of action of various drugs upon these substances.", "contents": "Circadian rhythm of cyclic nucleotide and GABA levels in the rat brain. Daily variation in the levels of cyclic nucleotides and GABA was examined in seven brain regions of male Sprague-Dawley rats. Significant daily rhythm of cyclic AMP levels was found in the cerebellum and pons medulla oblongata. Circadian variation of cyclic GMP levels was found in the cerebellum, cerebral cortex, striatum, and hypothalamus. Daily variation of GABA levels was found in the pons medulla oblongata and striatum. Cyclic GMP in the pons medulla oblongata and GABA in the hypothalamus were found to exhibit ultradian variation of levels. These observed daily fluctuations of baseline levels should be considered when examining the duration of action of various drugs upon these substances."}
{"id": "PMID:232922", "title": "Action of various drugs with anti-inflammatory or anti-rheumatic properties on pleurisy due to Bordetella pertussis hypersensitivity in the rat.", "content": "The authors studied various drugs with anti-inflammatory or antirheumatic properties on pleurisy due to Bordetella pertussis hypersensitivity in the rat. The following compounds were studies according to various methods of treatment: indomethacin, phenylbutazone, cyclophosphamide, desonide, chloroquine, levamisole, D-penicillamine and sodium aurothiopropanol sulphonate. The action on the volume of pleural exudate and on cell events depended on the compounds and the conditions of treatment. Only gold salt produced no reduction in the pleural volume under all methods of treatment. All the compounds studied produced various degrees of significant modifications at the level of the cell events.", "contents": "Action of various drugs with anti-inflammatory or anti-rheumatic properties on pleurisy due to Bordetella pertussis hypersensitivity in the rat. The authors studied various drugs with anti-inflammatory or antirheumatic properties on pleurisy due to Bordetella pertussis hypersensitivity in the rat. The following compounds were studies according to various methods of treatment: indomethacin, phenylbutazone, cyclophosphamide, desonide, chloroquine, levamisole, D-penicillamine and sodium aurothiopropanol sulphonate. The action on the volume of pleural exudate and on cell events depended on the compounds and the conditions of treatment. Only gold salt produced no reduction in the pleural volume under all methods of treatment. All the compounds studied produced various degrees of significant modifications at the level of the cell events."}
{"id": "PMID:232923", "title": "Oxidation of NADH by melanin: effect of UV light and copper ions.", "content": "The oxidation reaction of NADH with synthetic melanin from L-dopa was investigated under various physicochemical conditions both by spectrophotometric measurements and ESR spectroscopy. The different amounts of NADH oxidized and the effects on the formation and decay of melanin free radicals were compared. Some hypotheses on a common physical mechanism involved in electron transfer reaction and in electron excitation through a liquid-solid interface are presented.", "contents": "Oxidation of NADH by melanin: effect of UV light and copper ions. The oxidation reaction of NADH with synthetic melanin from L-dopa was investigated under various physicochemical conditions both by spectrophotometric measurements and ESR spectroscopy. The different amounts of NADH oxidized and the effects on the formation and decay of melanin free radicals were compared. Some hypotheses on a common physical mechanism involved in electron transfer reaction and in electron excitation through a liquid-solid interface are presented."}
{"id": "PMID:232929", "title": "[Radiologic diagnosis of the retroperitoneal masses (author's transl)].", "content": "A series of 75 patients with retroperitoneal masses (60 malignant and 15 benign tumours) have been studied. Urography and angiography were employed. The results of the two methods are correlated. The following criteria are taken into consideration: a) site; b) nature; c) extension of the mass. The importance of a precise definition of the extension of the tumour is stressed. In fact this can greatly influence the choice of the therapy.", "contents": "[Radiologic diagnosis of the retroperitoneal masses (author's transl)]. A series of 75 patients with retroperitoneal masses (60 malignant and 15 benign tumours) have been studied. Urography and angiography were employed. The results of the two methods are correlated. The following criteria are taken into consideration: a) site; b) nature; c) extension of the mass. The importance of a precise definition of the extension of the tumour is stressed. In fact this can greatly influence the choice of the therapy."}
{"id": "PMID:232930", "title": "[Multiple cutaneous neoplasms following repeated fluoroscopic examinations. (A case of clear-cell malignant hidradenoma associated with intra-epidermal epitheliomas of the Bowen type)].", "content": "A case of some neoplastic lesions of the skin of the back, arisen on undamaged skin, in a patient who underwent therapeutic pneumothorax and was submitted to several fluoroscopic examinations for pulmonary tuberculosis many years ago, is reported and discussed. An attempt of evaluation of the exposure to the ionizing radiations received by the interscapular region of the patient is made. The malignant clear-cell hidradenoma is a very rarely observed carcinoma: nine cases have been so far described.", "contents": "[Multiple cutaneous neoplasms following repeated fluoroscopic examinations. (A case of clear-cell malignant hidradenoma associated with intra-epidermal epitheliomas of the Bowen type)]. A case of some neoplastic lesions of the skin of the back, arisen on undamaged skin, in a patient who underwent therapeutic pneumothorax and was submitted to several fluoroscopic examinations for pulmonary tuberculosis many years ago, is reported and discussed. An attempt of evaluation of the exposure to the ionizing radiations received by the interscapular region of the patient is made. The malignant clear-cell hidradenoma is a very rarely observed carcinoma: nine cases have been so far described."}
{"id": "PMID:232941", "title": "Ligandin subunits and hepatocellular carcinoma in man and rat.", "content": "Covalent binding of activated azo dye and methyl cholanthrene carcinogens preferentially occurs to subunit B of ligandin. This subunit contains 7 of ligandin's 9 cysteine residues which, according to Ketterer et al, are the site of covalent carcinogen binding. Subunit B appears to be cytoplasmic and intranuclear. We postulate that binding of activated carcinogens to subunit B may facilitate their transfer from cytoplasm to nucleus. Rat and human primary liver cell cancers often contain ligandin which is released into the circulation. In patients at risk for, or suspected of having primary liver cell cancer, increased serum ligandin concentrations may have diagnostic value.", "contents": "Ligandin subunits and hepatocellular carcinoma in man and rat. Covalent binding of activated azo dye and methyl cholanthrene carcinogens preferentially occurs to subunit B of ligandin. This subunit contains 7 of ligandin's 9 cysteine residues which, according to Ketterer et al, are the site of covalent carcinogen binding. Subunit B appears to be cytoplasmic and intranuclear. We postulate that binding of activated carcinogens to subunit B may facilitate their transfer from cytoplasm to nucleus. Rat and human primary liver cell cancers often contain ligandin which is released into the circulation. In patients at risk for, or suspected of having primary liver cell cancer, increased serum ligandin concentrations may have diagnostic value."}
{"id": "PMID:232937", "title": "Superoxide, hydrogen peroxide, and oxygen tolerance of oxygen-sensitive mutants of Escherichia coli.", "content": "Oxygen-intolerant mutants of Escherichia coli K12 were selected by a replica plating technique after treatment with the mutagen, N-methyl-N'-nitro-N-nitrosoguanidine, to a lethality of 99.5%. One group of mutants had lost the ability to induce both peroxidase and catalase when exposed to oxygen but retained the ability to induce the manganese-superoxide dismutase. The second group of mutants had lost the ability to induce the activity of all these enzymes. Failure to induce peroxidase and catalase was associated with enhanced susceptibility of the bacteria to the lethal effect of oxygen. When a member of the first group of mutants was prevented from producing the manganese-superoxide dismutase by the presence of puromycin, its susceptibility to the lethal effects of oxygen was greatly increased. Two types of revertants were seen. In one group the ability to induce enzyme activity was recovered and was accompanied by the return of oxygen tolerance. Members of the other group lost the ability to respire and, therefore, no longer produced O2- AND H2O2. These results indicated that enzymic scavenging of both H2O2 and O2- provides an important defense against oxygen toxicity. The parallel loss of peroxidase and catalase, which was seen in all mutants, suggests that these enzymes constitute a precursor-product pair in E. coli. The parallel loss in two of these mutants of peroxidase, catalase, and the manganese-superoxide dismutase suggests a control linkage for these enzymes, the basis of which remains  to be explored.", "contents": "Superoxide, hydrogen peroxide, and oxygen tolerance of oxygen-sensitive mutants of Escherichia coli. Oxygen-intolerant mutants of Escherichia coli K12 were selected by a replica plating technique after treatment with the mutagen, N-methyl-N'-nitro-N-nitrosoguanidine, to a lethality of 99.5%. One group of mutants had lost the ability to induce both peroxidase and catalase when exposed to oxygen but retained the ability to induce the manganese-superoxide dismutase. The second group of mutants had lost the ability to induce the activity of all these enzymes. Failure to induce peroxidase and catalase was associated with enhanced susceptibility of the bacteria to the lethal effect of oxygen. When a member of the first group of mutants was prevented from producing the manganese-superoxide dismutase by the presence of puromycin, its susceptibility to the lethal effects of oxygen was greatly increased. Two types of revertants were seen. In one group the ability to induce enzyme activity was recovered and was accompanied by the return of oxygen tolerance. Members of the other group lost the ability to respire and, therefore, no longer produced O2- AND H2O2. These results indicated that enzymic scavenging of both H2O2 and O2- provides an important defense against oxygen toxicity. The parallel loss of peroxidase and catalase, which was seen in all mutants, suggests that these enzymes constitute a precursor-product pair in E. coli. The parallel loss in two of these mutants of peroxidase, catalase, and the manganese-superoxide dismutase suggests a control linkage for these enzymes, the basis of which remains  to be explored."}
{"id": "PMID:232942", "title": "Characterization of an angiotensin binding site in rabbit renomedullary interstitial cells in tissue culture: correlation with prostaglandin biosynthesis.", "content": "High affinity binding sites for angiotensin II have been identified and characterized in rabbit renomedullary interstitial cells in tissue culture. Binding studies were performed using monoiodinated angiotensin II of high specific activity; the angiotensinase inhibitors dithiothreitol and phenylmethylsulfonylfluoride were added to the incubation medium to retard degradation of the labeled hormone. Uptake of 125I angiotensin II was maximal at pH 7.4 and Scatchard analysis indicated a single binding site with a KD of 3.1 nM. Binding to a particulate preparation of the cells was rapid and reversible. Competition for binding by angiotensin II analogs correlated with their biologic potencies: (Sar1Ala8) AII greater than AII greater than (desAsp1) AII greater than greater than 3-8 hexapeptide. The 1-7 heptapeptide was completely ineffective in displacing the labeled angiotensin II from its binding sites. Angiotensin II directly stimulated prostaglandin (PG) biosynthesis by the renomedullary cells in tissue culture; the concentration of angiotensin II that resulted in half maximal stimulation of PG biosynthesis (6.5 nM) was similar to the concentration of angiotensin II that resulted in half maximal occupancy of binding sites (3.1 nM). These results suggest that the renomedullary cells may provide a model homogeneous tissue for the study of the angiotensin receptor and the hormonal regulation of prostaglandin biosynthesis.", "contents": "Characterization of an angiotensin binding site in rabbit renomedullary interstitial cells in tissue culture: correlation with prostaglandin biosynthesis. High affinity binding sites for angiotensin II have been identified and characterized in rabbit renomedullary interstitial cells in tissue culture. Binding studies were performed using monoiodinated angiotensin II of high specific activity; the angiotensinase inhibitors dithiothreitol and phenylmethylsulfonylfluoride were added to the incubation medium to retard degradation of the labeled hormone. Uptake of 125I angiotensin II was maximal at pH 7.4 and Scatchard analysis indicated a single binding site with a KD of 3.1 nM. Binding to a particulate preparation of the cells was rapid and reversible. Competition for binding by angiotensin II analogs correlated with their biologic potencies: (Sar1Ala8) AII greater than AII greater than (desAsp1) AII greater than greater than 3-8 hexapeptide. The 1-7 heptapeptide was completely ineffective in displacing the labeled angiotensin II from its binding sites. Angiotensin II directly stimulated prostaglandin (PG) biosynthesis by the renomedullary cells in tissue culture; the concentration of angiotensin II that resulted in half maximal stimulation of PG biosynthesis (6.5 nM) was similar to the concentration of angiotensin II that resulted in half maximal occupancy of binding sites (3.1 nM). These results suggest that the renomedullary cells may provide a model homogeneous tissue for the study of the angiotensin receptor and the hormonal regulation of prostaglandin biosynthesis."}
{"id": "PMID:232935", "title": "Virulence factors of Clostridium perfringens.", "content": "Clostridium perfringens produces a variety of virulence factors. The mechanism of action of these factors usually falls into one of three groups. Some of these virulence factors, such as the alpha toxin, which is phospholipase C, and the kappa toxin, which is a collagenase, are enzymes that hydrolyze substances essential to the integrity of membranes or other body structures. Other virulence factors, such as the beta, episolon, and iota toxins, act primarily on the vascular endothelium, causing increased capillary permeability, especially in the brain. Still others, such as the delta and theta toxins, are essentially hemolysins. Theta toxin is similar in action and serologically related to streptolysin O.", "contents": "Virulence factors of Clostridium perfringens. Clostridium perfringens produces a variety of virulence factors. The mechanism of action of these factors usually falls into one of three groups. Some of these virulence factors, such as the alpha toxin, which is phospholipase C, and the kappa toxin, which is a collagenase, are enzymes that hydrolyze substances essential to the integrity of membranes or other body structures. Other virulence factors, such as the beta, episolon, and iota toxins, act primarily on the vascular endothelium, causing increased capillary permeability, especially in the brain. Still others, such as the delta and theta toxins, are essentially hemolysins. Theta toxin is similar in action and serologically related to streptolysin O."}
{"id": "PMID:232936", "title": "Experimental animal models for anaerobic infections.", "content": "An experimental animal model that stimulates the mixed aerobic-anaerobic microflora of intraabdominal sepsis was used to study antimicrobial efficacy in vivo. Treatment of infected rats with chloramphenicol resulted in only a modest reduction in the percentage of animals surviving infection with abscesses at necropsy. This unanticipated observation led to further exploration of the predominant anaerobes associated with the experimental infection. In vitro cultures of Bacteroides fragilis, susceptible to chloramphenicol in traditional tests, were capable of reducing chloramphenicol to its aryl amine derivative, which is biologically inactive. In contrast, metronidazole, an antimicrobial agent active against anaerobes, reduced the coli-metronidazole, an antimicrobial agent active against anaerobes, reduced the coli-form-associated mortality in this animal model. Subsequent studies showed that this reduction in mortality is dependent on the presence of an anaerobe and that the levels of Escherichia coli in mixed continuous culture with B. fragilis are reduced by addition of metronidazole. This reduction following addition of metronidazole was not observed either in a pure culture of E. coli or when clindamycin was added to a mixed culture. In a modification of the previously described model, infective material was placed subcutaneously into Wistar rats. Studies with this model suggested that the host's response to bacterial challenge is dependent on the site of infection and that organotropism of the implanted bacterial species is an important determinant of infection.", "contents": "Experimental animal models for anaerobic infections. An experimental animal model that stimulates the mixed aerobic-anaerobic microflora of intraabdominal sepsis was used to study antimicrobial efficacy in vivo. Treatment of infected rats with chloramphenicol resulted in only a modest reduction in the percentage of animals surviving infection with abscesses at necropsy. This unanticipated observation led to further exploration of the predominant anaerobes associated with the experimental infection. In vitro cultures of Bacteroides fragilis, susceptible to chloramphenicol in traditional tests, were capable of reducing chloramphenicol to its aryl amine derivative, which is biologically inactive. In contrast, metronidazole, an antimicrobial agent active against anaerobes, reduced the coli-metronidazole, an antimicrobial agent active against anaerobes, reduced the coli-form-associated mortality in this animal model. Subsequent studies showed that this reduction in mortality is dependent on the presence of an anaerobe and that the levels of Escherichia coli in mixed continuous culture with B. fragilis are reduced by addition of metronidazole. This reduction following addition of metronidazole was not observed either in a pure culture of E. coli or when clindamycin was added to a mixed culture. In a modification of the previously described model, infective material was placed subcutaneously into Wistar rats. Studies with this model suggested that the host's response to bacterial challenge is dependent on the site of infection and that organotropism of the implanted bacterial species is an important determinant of infection."}
{"id": "PMID:232945", "title": "A new function for ceruloplasmin as an acute-phase reactant in inflammation: a scavenger of superoxide anion radicals.", "content": "In summary, purified human ceruloplasmin inhibits several reactions mediated by superoxide anion in a fashion consistent with an ability to scavenge this free radical. It must be pointed out, however, that on a weight basis, the superoxide-scavenging activity of ceruloplasmin is substantially less than that of purified human erythrocyte superoxide dismutase. Nevertheless, since superoxide dismutase is almost exclusively an intracellular enzyme, ceruloplasmin probably represents the major circulating scavenger of superoxide anion radicals. The level of superoxide dismutase in human plasma has been reported to be 0.7 microgram/ml. It is not clear, however, how this was measured. We have found that concentrations of plasma exceeding 10% (v/v) interfere significantly with the assays routinely employed for detecting superoxide-scavenging activity. Consequently, we have not yet been able to quantify the superoxide-scavenging activity of either ceruloplasmin or superoxide dismutase in whole human plasma. Thus, we can only speculate that under conditions where levels of ceruloplasmin are markedly elevated, as during pregnancy, during acute infections, or in association with inflammatory diseases (such as rheumatoid arthritis), this acute-phase reactant may play a major role as a circulating scavenger of oxygen-derived free radicals.", "contents": "A new function for ceruloplasmin as an acute-phase reactant in inflammation: a scavenger of superoxide anion radicals. In summary, purified human ceruloplasmin inhibits several reactions mediated by superoxide anion in a fashion consistent with an ability to scavenge this free radical. It must be pointed out, however, that on a weight basis, the superoxide-scavenging activity of ceruloplasmin is substantially less than that of purified human erythrocyte superoxide dismutase. Nevertheless, since superoxide dismutase is almost exclusively an intracellular enzyme, ceruloplasmin probably represents the major circulating scavenger of superoxide anion radicals. The level of superoxide dismutase in human plasma has been reported to be 0.7 microgram/ml. It is not clear, however, how this was measured. We have found that concentrations of plasma exceeding 10% (v/v) interfere significantly with the assays routinely employed for detecting superoxide-scavenging activity. Consequently, we have not yet been able to quantify the superoxide-scavenging activity of either ceruloplasmin or superoxide dismutase in whole human plasma. Thus, we can only speculate that under conditions where levels of ceruloplasmin are markedly elevated, as during pregnancy, during acute infections, or in association with inflammatory diseases (such as rheumatoid arthritis), this acute-phase reactant may play a major role as a circulating scavenger of oxygen-derived free radicals."}
{"id": "PMID:232949", "title": "[Experiments to obtain and test a cell-culture rotavirus-precipitating antigen].", "content": "The location of the rotaviral precipitating antigen and the possibility for its production from cattle rotaviral strains adapted on cell cultures of calf kidney were investigated. Highest titer antigen was produced by concentration with ammonium sulfate simultaneously from the maintaining medium and from the cell monolayer. Comparative studies on the antigenic and physico-chemical properties of the cell-cultural and the faeces rotaviral precipitating antigen were made. The identity of both antigens was proven by the immunodiffuse reaction and by their resistance to ether and tripsine. A considerably higher temperature sensitivity was established of the cell-cultural precipitating antigen as compared to that from faeces. The precipitating antigen was used for confirming the presence of antirotaviral antibodies in the serums of cattle, man and sheep.", "contents": "[Experiments to obtain and test a cell-culture rotavirus-precipitating antigen]. The location of the rotaviral precipitating antigen and the possibility for its production from cattle rotaviral strains adapted on cell cultures of calf kidney were investigated. Highest titer antigen was produced by concentration with ammonium sulfate simultaneously from the maintaining medium and from the cell monolayer. Comparative studies on the antigenic and physico-chemical properties of the cell-cultural and the faeces rotaviral precipitating antigen were made. The identity of both antigens was proven by the immunodiffuse reaction and by their resistance to ether and tripsine. A considerably higher temperature sensitivity was established of the cell-cultural precipitating antigen as compared to that from faeces. The precipitating antigen was used for confirming the presence of antirotaviral antibodies in the serums of cattle, man and sheep."}
{"id": "PMID:232951", "title": "[Neurologic syndromes affecting the shoulder (author's transl)].", "content": "A number of locally defined as well as generalised diseases of the peripheral nervous system is manifested in the shoulderarm region besides lesions of individual nerves through traumas or as a result of pressure. Radicular syndromes are particularly frequent. These are based on prolapsed disks or degenerative changes of the cervical vertebral column. We must differentiate between these syndromes and the often rather unknown neuralgic amytrophy of the shoulder. Our experience has shown that in too many cases, paralysis of the plexus cervico-brachialis is assumed, although this occurs almost exclusively on the basis of traumatic violence, much rarer due to pressure. In such cases, the physician should look for the scalenus syndrome, the costoclavicular syndrome, and the hyperabduction syndrome. As a rule, pain is the most prominent symptom in plexus pareses through new growths, eg Pancoast's tumour. In such cases, a clear distinction must be made against bursitis of the shoulder (periarthritis humeroscapularis), in which there are no neurogenic changes, but only myogenic changes manifested in the electromyogram. If the sudden pain is accompanied by swelling and weakness of the arm, there is every likelihood of the existence of Paget-von Schr\u00f6tter's syndrome. A remarkably painless deformation of the shoulder joint should also suggest neurogenic arthropathy in syringomyelia. The physician should also consider disturbances of distant origin, for example in the region of the carpal tunnel, with pain radiating to the shoulder in the manner of brachialgia paraesthetica. Finally, any noticeable weakness or muscular atrophy in the shoulder region should suggest a disease of the neuromuscular system, mainly progressive muscular dystrophy or the rare shoulder girdle type of amyotrophic lateral sclerosis.", "contents": "[Neurologic syndromes affecting the shoulder (author's transl)]. A number of locally defined as well as generalised diseases of the peripheral nervous system is manifested in the shoulderarm region besides lesions of individual nerves through traumas or as a result of pressure. Radicular syndromes are particularly frequent. These are based on prolapsed disks or degenerative changes of the cervical vertebral column. We must differentiate between these syndromes and the often rather unknown neuralgic amytrophy of the shoulder. Our experience has shown that in too many cases, paralysis of the plexus cervico-brachialis is assumed, although this occurs almost exclusively on the basis of traumatic violence, much rarer due to pressure. In such cases, the physician should look for the scalenus syndrome, the costoclavicular syndrome, and the hyperabduction syndrome. As a rule, pain is the most prominent symptom in plexus pareses through new growths, eg Pancoast's tumour. In such cases, a clear distinction must be made against bursitis of the shoulder (periarthritis humeroscapularis), in which there are no neurogenic changes, but only myogenic changes manifested in the electromyogram. If the sudden pain is accompanied by swelling and weakness of the arm, there is every likelihood of the existence of Paget-von Schr\u00f6tter's syndrome. A remarkably painless deformation of the shoulder joint should also suggest neurogenic arthropathy in syringomyelia. The physician should also consider disturbances of distant origin, for example in the region of the carpal tunnel, with pain radiating to the shoulder in the manner of brachialgia paraesthetica. Finally, any noticeable weakness or muscular atrophy in the shoulder region should suggest a disease of the neuromuscular system, mainly progressive muscular dystrophy or the rare shoulder girdle type of amyotrophic lateral sclerosis."}
{"id": "PMID:232956", "title": "[Influence of straw manuring on the biological activity of a lessiv\u00e9 chernozem (author's transl)].", "content": "In a long-term experiment, the influence of straw manuring in spring and autumn on the biological activity of a lessive chernozem soil was examined. The quantity of carbon dioxide, evolved by the plots during May and June, showed an increase in soil respiration by straw manuring. Increasing amounts of nitrogen, given together with straw, had no significant influence on the quantity of carbon dioxide evolved. The base respiration, however, showed increasing rates proportional to increasing amounts of nitrogen. The variants manured with straw in autumn were superior to those manured in spring. For covering the efficiency of soil respiration, the field method applied noes not seem suitable. With high N-supply (200 kg/ka), the relative respiration rates show good stability of the organic substance, present in soil. This stability is higher with straw manuring in spring than in autumn. Straw supply in autumn influences the yield more favourably. Direct relation between the quantity of carbon dioxide evolved and yield cannot be inferred.", "contents": "[Influence of straw manuring on the biological activity of a lessiv\u00e9 chernozem (author's transl)]. In a long-term experiment, the influence of straw manuring in spring and autumn on the biological activity of a lessive chernozem soil was examined. The quantity of carbon dioxide, evolved by the plots during May and June, showed an increase in soil respiration by straw manuring. Increasing amounts of nitrogen, given together with straw, had no significant influence on the quantity of carbon dioxide evolved. The base respiration, however, showed increasing rates proportional to increasing amounts of nitrogen. The variants manured with straw in autumn were superior to those manured in spring. For covering the efficiency of soil respiration, the field method applied noes not seem suitable. With high N-supply (200 kg/ka), the relative respiration rates show good stability of the organic substance, present in soil. This stability is higher with straw manuring in spring than in autumn. Straw supply in autumn influences the yield more favourably. Direct relation between the quantity of carbon dioxide evolved and yield cannot be inferred."}
{"id": "PMID:232957", "title": "Biological oxidation of ammoniacal fertilizers as affected by the physical properties of soil.", "content": "The study was made on the nitrification of ammonium sulphate and ammonium nitrate in nine soils, widely different in their texture and calcium carbonate content. Fertilizers were added to the soils in amounts to represent a cross section of a fertilizer band, ranging from 100 to 1000 ppm ammoniacal nitrogen. Results indicate the high capacity of all soils for nitrifying appreciable amounts of ammonium nitrogen during a short time. Both fertilizers nitrified rapidly and at about the same rate when applied in amounts less than 500 ppm NH4-N, but nitrification was rather rapid in soils rich in clay mineral and harbouring a denser population of nitrifying bacteria. At higher levels of NH4-N additions, ammonium as sulphate nitrified faster than as nitrate, especially in the high concentrations of NH4-N. Nitrite was detected in small amounts of less than 10 ppm in some soils, particularly in the coarse-textured ones, regardless of the type and amount of the fertilizer applied. Considerable amounts of nitrite accumulated in other soils and persisted for long time as a result of addition of high levels of NH4-N, especially in the form of ammonium nitrate.", "contents": "Biological oxidation of ammoniacal fertilizers as affected by the physical properties of soil. The study was made on the nitrification of ammonium sulphate and ammonium nitrate in nine soils, widely different in their texture and calcium carbonate content. Fertilizers were added to the soils in amounts to represent a cross section of a fertilizer band, ranging from 100 to 1000 ppm ammoniacal nitrogen. Results indicate the high capacity of all soils for nitrifying appreciable amounts of ammonium nitrogen during a short time. Both fertilizers nitrified rapidly and at about the same rate when applied in amounts less than 500 ppm NH4-N, but nitrification was rather rapid in soils rich in clay mineral and harbouring a denser population of nitrifying bacteria. At higher levels of NH4-N additions, ammonium as sulphate nitrified faster than as nitrate, especially in the high concentrations of NH4-N. Nitrite was detected in small amounts of less than 10 ppm in some soils, particularly in the coarse-textured ones, regardless of the type and amount of the fertilizer applied. Considerable amounts of nitrite accumulated in other soils and persisted for long time as a result of addition of high levels of NH4-N, especially in the form of ammonium nitrate."}
{"id": "PMID:232958", "title": "[Postovulatory and post-implantation inhibition of fertility--general account (author's transl)].", "content": "Latest knowledge about interception and induced menstruation is discussed. Interception (postovulatory inhibition of fertility) can be undertaken by using oestrogens, anti-oestrogens and gestagens as well as non-steroid compounds. Induced menstruation is discussed as a method of post-implantation inhibition of fertility. Induction of menstruation, that is post-implantation contraception, will be feasible by means of anti-gestagens or inhibitors ov ovarian steroid biosynthesis. While most various research efforts have been undertaken, no practicable procedure has become available as yet.", "contents": "[Postovulatory and post-implantation inhibition of fertility--general account (author's transl)]. Latest knowledge about interception and induced menstruation is discussed. Interception (postovulatory inhibition of fertility) can be undertaken by using oestrogens, anti-oestrogens and gestagens as well as non-steroid compounds. Induced menstruation is discussed as a method of post-implantation inhibition of fertility. Induction of menstruation, that is post-implantation contraception, will be feasible by means of anti-gestagens or inhibitors ov ovarian steroid biosynthesis. While most various research efforts have been undertaken, no practicable procedure has become available as yet."}
{"id": "PMID:232960", "title": "The influence of growth temperature on the heat stability of inorganic pyrophosphatase from crude extracts of Bacillus stearothermophilus.", "content": "Inorganic pyrophosphatase activity of crude extracts from Bacillus stearothermophilus adapts its thermostability to the growth temperature of the cells. Magnesium ions increase the stability of the enzyme in all cases. Depending on the growth temperature of the cells two pyrophosphatase species differing in their molecular weights and heat stabilities have been detected.", "contents": "The influence of growth temperature on the heat stability of inorganic pyrophosphatase from crude extracts of Bacillus stearothermophilus. Inorganic pyrophosphatase activity of crude extracts from Bacillus stearothermophilus adapts its thermostability to the growth temperature of the cells. Magnesium ions increase the stability of the enzyme in all cases. Depending on the growth temperature of the cells two pyrophosphatase species differing in their molecular weights and heat stabilities have been detected."}
{"id": "PMID:232961", "title": "An ouabain-insensitive Na-ATPase of the arterial vascular muscle cell and its relation to ouabain-sensitive Na,K-ATPase.", "content": "A Na+-stimulated, Mg++-requiring ATPase (Na-ATPase), which is insensitive to ouabain, has been demonstrated in the carotis and coronary arteries of different species. In dependence on the sodium concentration half-maximal activities of Na-ATPase are found in the range from 16 to 24 mM Na+. A replacement of Mg++ by Ca++ leads to a partial loss of activity. It does not, however, change its sensitivity to sodium. Compared to Na,K-ATPase, the Na-ATPase shows a considerably lower sensitivity to calcium. p-Chloro-mercuribenzoate, N-ethylmaleinimide, chloropromazine, sodium fluoride, ethanol and sodium azide influence the activity of the Na-ATPase in a characteristic way corresponding to the reactivity of Na,K-ATPase. Noradrenaline and isoprenaline do not lead to any significant change of its activity. The possible separate existence of a Na-ATPase independent of Na,K-ATPase, as well as its potential importance for cellular metabolism are discussed.", "contents": "An ouabain-insensitive Na-ATPase of the arterial vascular muscle cell and its relation to ouabain-sensitive Na,K-ATPase. A Na+-stimulated, Mg++-requiring ATPase (Na-ATPase), which is insensitive to ouabain, has been demonstrated in the carotis and coronary arteries of different species. In dependence on the sodium concentration half-maximal activities of Na-ATPase are found in the range from 16 to 24 mM Na+. A replacement of Mg++ by Ca++ leads to a partial loss of activity. It does not, however, change its sensitivity to sodium. Compared to Na,K-ATPase, the Na-ATPase shows a considerably lower sensitivity to calcium. p-Chloro-mercuribenzoate, N-ethylmaleinimide, chloropromazine, sodium fluoride, ethanol and sodium azide influence the activity of the Na-ATPase in a characteristic way corresponding to the reactivity of Na,K-ATPase. Noradrenaline and isoprenaline do not lead to any significant change of its activity. The possible separate existence of a Na-ATPase independent of Na,K-ATPase, as well as its potential importance for cellular metabolism are discussed."}
{"id": "PMID:232964", "title": "Basal, cAMP- and cGMP-dependent protein kinases in human brain tumors.", "content": "Since the effects of cyclic nucleotides are mediated via protein kinases activation, we have studied the properties and regulation of these enzymes in cytosol and particulate fraction of normal cerebral tissues and of some human brain tumors. We found that distribution and activity of cyclic nucleotide-dependent protein kinases are regulated differently among various brain tumors and in comparison to normal gray and white matter. Pathological tissues show an higher cGMP-dependent protein kinase and this biochemical pattern is particularly evident in tumors with more pronounced malignancy. These data further confirm the hypothesis of a correlation between the increase of cGMP function and cellular growth and malignancy.", "contents": "Basal, cAMP- and cGMP-dependent protein kinases in human brain tumors. Since the effects of cyclic nucleotides are mediated via protein kinases activation, we have studied the properties and regulation of these enzymes in cytosol and particulate fraction of normal cerebral tissues and of some human brain tumors. We found that distribution and activity of cyclic nucleotide-dependent protein kinases are regulated differently among various brain tumors and in comparison to normal gray and white matter. Pathological tissues show an higher cGMP-dependent protein kinase and this biochemical pattern is particularly evident in tumors with more pronounced malignancy. These data further confirm the hypothesis of a correlation between the increase of cGMP function and cellular growth and malignancy."}
{"id": "PMID:232965", "title": "Mechanism of the cerebrocortical vasodilatation during anoxia.", "content": "The possible role of cerebrocortical ion homeostasis, NAD/NADH redox state and of cortical oxygen tension was investigated in the initiation of hypoxic cortical vasodilatation. In addition, changes in cerebrocortical extracellular concentrations of Na+, K+, and Cl- during anoxia were studied. The results were as follows. a) The cerebrocortical reflectance decrease, e.g. cerebral vasodilatation, lagged behind the cortical pO2 decrease by 1-2 sec, but preceded the decrease of arterial blood pressure and ECoG as well as the extracellular Na+, K+, Cl- increases by 20-30 sec. Since the cortical pO2 decreased first and the ion changes lagged behind the onset of vasodilatation by 20-30 sec, it is suggested that the CBF increase in hypoxia is mediated via the cortical pO2 decrease. b) A significant NAD reduction was already present after 20 sec. of nitrogen breathing. Since the ECoG and MABP decreased, and K+ activity increased much later than this, it is presumed that the NAD reduction during the first 30-40 sec of anoxia indicates an increased rate of glycolysis, but not mitochondrial hypoxia. c) In the predepolarization phase a 17% K+, 4% Na+, 5% Cl- increase is probably the result of a reduction of the extracellular spaces caused by water movement and by the migration of Na+ and Cl- from the extracellular to the intracellular space. The large K+, Na+, Cl- changes during terminal depolarization can be interpreted as a result of the failure of the membrane bound Na+ -K+ pump and of the altered ion permeability of the cell membranes.", "contents": "Mechanism of the cerebrocortical vasodilatation during anoxia. The possible role of cerebrocortical ion homeostasis, NAD/NADH redox state and of cortical oxygen tension was investigated in the initiation of hypoxic cortical vasodilatation. In addition, changes in cerebrocortical extracellular concentrations of Na+, K+, and Cl- during anoxia were studied. The results were as follows. a) The cerebrocortical reflectance decrease, e.g. cerebral vasodilatation, lagged behind the cortical pO2 decrease by 1-2 sec, but preceded the decrease of arterial blood pressure and ECoG as well as the extracellular Na+, K+, Cl- increases by 20-30 sec. Since the cortical pO2 decreased first and the ion changes lagged behind the onset of vasodilatation by 20-30 sec, it is suggested that the CBF increase in hypoxia is mediated via the cortical pO2 decrease. b) A significant NAD reduction was already present after 20 sec. of nitrogen breathing. Since the ECoG and MABP decreased, and K+ activity increased much later than this, it is presumed that the NAD reduction during the first 30-40 sec of anoxia indicates an increased rate of glycolysis, but not mitochondrial hypoxia. c) In the predepolarization phase a 17% K+, 4% Na+, 5% Cl- increase is probably the result of a reduction of the extracellular spaces caused by water movement and by the migration of Na+ and Cl- from the extracellular to the intracellular space. The large K+, Na+, Cl- changes during terminal depolarization can be interpreted as a result of the failure of the membrane bound Na+ -K+ pump and of the altered ion permeability of the cell membranes."}
{"id": "PMID:232962", "title": "[Neurotoxicity of formyl leurosine. An experimental and clinical study (author's transl)].", "content": "Leg paralysis and wallerian degeneration of sciatic nerve fibres have been produced in rats by intraneural injection of 0.5, 1 or 5 microgram of vincristine (VCR) or formyl leurosine (FLR) dissolved in 5 microliter of saline. Nerve lesions were dose-related, and were similar for equal concentrations of the two drugs. Six patients received one to three 5-day courses of FLR. The total dose of FLR administered ranged from 15 to 131 mg (mean 83 mg). Clinical signs of peripheral neuropathy were absent in four patients, and limited to orthostatic hypotension in one case and transient depression of reflexes in another. Motor conduction velocities measured in four peripheral nerves, and muscle evoked potentials remained unchanged throughout the treatment in all patients.", "contents": "[Neurotoxicity of formyl leurosine. An experimental and clinical study (author's transl)]. Leg paralysis and wallerian degeneration of sciatic nerve fibres have been produced in rats by intraneural injection of 0.5, 1 or 5 microgram of vincristine (VCR) or formyl leurosine (FLR) dissolved in 5 microliter of saline. Nerve lesions were dose-related, and were similar for equal concentrations of the two drugs. Six patients received one to three 5-day courses of FLR. The total dose of FLR administered ranged from 15 to 131 mg (mean 83 mg). Clinical signs of peripheral neuropathy were absent in four patients, and limited to orthostatic hypotension in one case and transient depression of reflexes in another. Motor conduction velocities measured in four peripheral nerves, and muscle evoked potentials remained unchanged throughout the treatment in all patients."}
{"id": "PMID:232966", "title": "Effect of arterial hypoxia on the cerebrocortical redox state, vascular volume, oxygen tension, electrical activity and potassium ion concentration.", "content": "The effect of different degrees of arterial hypoxia on cerebrocortical NAD/NADH redox state, reflectance, oxygen tension, extracellular potassium ion concentration, ECoG and arterial blood pressure was investigated in rats. The results may be summarized as follows. a) The decrease of cortical pO2 preceded the dilatation of cortical vessels by 15-20 sec but the changes in cortical extracellular potassium ion concentration, ECoG and arterial blood pressure started later than the vasodilatation. These results give further support to the regulatory role of cortical pO2 decrease in the initiation of cerebrocortical vasodilatation during arterial hypoxia. b) Since the K+ concentration of the brain cortex and the ECoG did not change in mild arterial hypoxia, the significant NAD reduction obtained in this experimental group is likely to be of cytoplasmic origin. The same conclusion applies to the initial periods of severe arterial hypoxia. On the basis of the extent of NAD reduction during various degrees of arterial hypoxia it is concluded that about 30% of the NAD reduction occurring in anoxia is of cytoplasmic origin. c) When the animals were ventilated with a gas mixture containing 4-7% oxygen, the brain cortex became nearly anoxic, partly because of the gradual decrease of arterial blood pressure. Finally, the mechanism of potassium leakage is identical under prolonged severe arterial hypoxaemia and on anoxic terminal depolarization.", "contents": "Effect of arterial hypoxia on the cerebrocortical redox state, vascular volume, oxygen tension, electrical activity and potassium ion concentration. The effect of different degrees of arterial hypoxia on cerebrocortical NAD/NADH redox state, reflectance, oxygen tension, extracellular potassium ion concentration, ECoG and arterial blood pressure was investigated in rats. The results may be summarized as follows. a) The decrease of cortical pO2 preceded the dilatation of cortical vessels by 15-20 sec but the changes in cortical extracellular potassium ion concentration, ECoG and arterial blood pressure started later than the vasodilatation. These results give further support to the regulatory role of cortical pO2 decrease in the initiation of cerebrocortical vasodilatation during arterial hypoxia. b) Since the K+ concentration of the brain cortex and the ECoG did not change in mild arterial hypoxia, the significant NAD reduction obtained in this experimental group is likely to be of cytoplasmic origin. The same conclusion applies to the initial periods of severe arterial hypoxia. On the basis of the extent of NAD reduction during various degrees of arterial hypoxia it is concluded that about 30% of the NAD reduction occurring in anoxia is of cytoplasmic origin. c) When the animals were ventilated with a gas mixture containing 4-7% oxygen, the brain cortex became nearly anoxic, partly because of the gradual decrease of arterial blood pressure. Finally, the mechanism of potassium leakage is identical under prolonged severe arterial hypoxaemia and on anoxic terminal depolarization."}
{"id": "PMID:232963", "title": "[Multicentric gliomas. Report of a case (author's transl)].", "content": "The criteria of culticentric gliomas, based upon histological data, were recently defined (Bartzdorf et al. 1963) and permits us to distinguish them clearly from multiple gliomas. The authors report an atypical case of glioma for which the diagnosis of multicentric gliomas has been established after anatomical and histological studies. Physiopathological hypotheses are discussed. Emphasis is placed on the clinical pictures, diagnostic techniques as well as evolution and therapeutic aspects.", "contents": "[Multicentric gliomas. Report of a case (author's transl)]. The criteria of culticentric gliomas, based upon histological data, were recently defined (Bartzdorf et al. 1963) and permits us to distinguish them clearly from multiple gliomas. The authors report an atypical case of glioma for which the diagnosis of multicentric gliomas has been established after anatomical and histological studies. Physiopathological hypotheses are discussed. Emphasis is placed on the clinical pictures, diagnostic techniques as well as evolution and therapeutic aspects."}
{"id": "PMID:232967", "title": "Intracellular oxygen tension and energy metabolism in the cat brain cortex during haemorrhagic shock.", "content": "The changes in intracellular oxygen tension and energy metabolism of the cat brain cortex were studied by surface fluororeflectometry during haemorrhagic shock. The results may be summarized as follows. (a) Intracellular oxygen tension, i.e. the maximum cortical NAD reduction obtained during nitrogen gas inhalation decreased gradually during the hypovolaemic phase of shock and finally, the brain cortex became ischaemic. (b) Partial uncoupling of the cerebrocortical mitochondrial respiration and oxidative phosphorylation appeared in the very early period of bleeding, as indicated by the overshot of the cortical NAD/NADH redox state towards oxidation subsequent to the cessation of nitrogen gas inhalation. Partial uncoupling of mitochondrial respiration and oxidative phosphorylation became more pronounced during the later phases of bleeding, finally, the mitochondrial electron transport stopped. In line with these changes the frequency and the amplitude of ECoG decreased gradually and markedly during the hypovolaemic phase of shock. (c) Microcirculation and energy metabolism of the cat brain cortex were severely and irreversibly damaged during the hypovolaemic phase of shock. This was clearly shown by the fact that in the majority of experiments the nitrogen anoxia after reinfusion failed to bring about changes in the cortical NAD/NADH redox state and the ECoG changes occurred during bleeding did not improve after reinfusion. It is concluded that the early disturbances of cerebrocortical energy metabolism play an important role in the development of neural and vascular lesions of the brain that occur during haemorrhagic shock.", "contents": "Intracellular oxygen tension and energy metabolism in the cat brain cortex during haemorrhagic shock. The changes in intracellular oxygen tension and energy metabolism of the cat brain cortex were studied by surface fluororeflectometry during haemorrhagic shock. The results may be summarized as follows. (a) Intracellular oxygen tension, i.e. the maximum cortical NAD reduction obtained during nitrogen gas inhalation decreased gradually during the hypovolaemic phase of shock and finally, the brain cortex became ischaemic. (b) Partial uncoupling of the cerebrocortical mitochondrial respiration and oxidative phosphorylation appeared in the very early period of bleeding, as indicated by the overshot of the cortical NAD/NADH redox state towards oxidation subsequent to the cessation of nitrogen gas inhalation. Partial uncoupling of mitochondrial respiration and oxidative phosphorylation became more pronounced during the later phases of bleeding, finally, the mitochondrial electron transport stopped. In line with these changes the frequency and the amplitude of ECoG decreased gradually and markedly during the hypovolaemic phase of shock. (c) Microcirculation and energy metabolism of the cat brain cortex were severely and irreversibly damaged during the hypovolaemic phase of shock. This was clearly shown by the fact that in the majority of experiments the nitrogen anoxia after reinfusion failed to bring about changes in the cortical NAD/NADH redox state and the ECoG changes occurred during bleeding did not improve after reinfusion. It is concluded that the early disturbances of cerebrocortical energy metabolism play an important role in the development of neural and vascular lesions of the brain that occur during haemorrhagic shock."}
{"id": "PMID:232968", "title": "Reactivity of the cerebrocortical vasculature and energy metabolism to direct cortical stimulation in haemorrhagic shock.", "content": "Direct electrical stimulation of the cerebral cortex was used to determine the changes of cortical carbohydrate and oxidative metabolism and of vascular reactivity during haemorrhagic shock. The results were as follows. 1. Electrical stimulation of the brain cortex applied in the control period led to a marked vasodilation and NAD reduction that was preceded in part of the experiments by a transient NADH oxidation. It is suggested that the increase in cortical NADH fluorescence observed during direct stimulation is due to the fact that the rate of cytoplasmic NADH production exceeded the rate of mitochondrial NADH oxidation and of the rate of H+-transport from the cytoplasm into the mitochondria. 2. The cerebrocortical vascular and NAD/NADH redox state responses induced by electrical stimulation changed in the early hypovolaemic phase of shock. At this time, electrical stimulation of the brain cortex led to NADH oxidation in the majority of the experiments or in some experiments, the stimulation did not bring about changes in the redox state of the cortex. The total loss of the reactivity to direct stimulation of the cerebrocortical vessels and of energy metabolism preceded the occurrence of cortical ischaemia during the hypovolaemic phase of shock. 3. Since after reinfusion of the shed blood, redox state and vasculature remained unresponsive to stimulation even in those experiments in which the cortical ischaemia improved, it is concluded that the carbohydrate and oxidative metabolism of the brain cortex were already irreversibly damaged in the early phase of hypovolaemic shock.", "contents": "Reactivity of the cerebrocortical vasculature and energy metabolism to direct cortical stimulation in haemorrhagic shock. Direct electrical stimulation of the cerebral cortex was used to determine the changes of cortical carbohydrate and oxidative metabolism and of vascular reactivity during haemorrhagic shock. The results were as follows. 1. Electrical stimulation of the brain cortex applied in the control period led to a marked vasodilation and NAD reduction that was preceded in part of the experiments by a transient NADH oxidation. It is suggested that the increase in cortical NADH fluorescence observed during direct stimulation is due to the fact that the rate of cytoplasmic NADH production exceeded the rate of mitochondrial NADH oxidation and of the rate of H+-transport from the cytoplasm into the mitochondria. 2. The cerebrocortical vascular and NAD/NADH redox state responses induced by electrical stimulation changed in the early hypovolaemic phase of shock. At this time, electrical stimulation of the brain cortex led to NADH oxidation in the majority of the experiments or in some experiments, the stimulation did not bring about changes in the redox state of the cortex. The total loss of the reactivity to direct stimulation of the cerebrocortical vessels and of energy metabolism preceded the occurrence of cortical ischaemia during the hypovolaemic phase of shock. 3. Since after reinfusion of the shed blood, redox state and vasculature remained unresponsive to stimulation even in those experiments in which the cortical ischaemia improved, it is concluded that the carbohydrate and oxidative metabolism of the brain cortex were already irreversibly damaged in the early phase of hypovolaemic shock."}
{"id": "PMID:232972", "title": "Extramammary Paget's disease. A critical reexamination.", "content": "Fifty-five patients with extramammary Paget's disease were the source of material for this study. Step-sections were done through most of the specimens. Clinical information, including follow-up, was obtained on 45 of the 55 patients. Extramammary Paget's disease could be divided histologically according to where Paget cells were found, namely: 1) wholly within the epidermis and the epithelial structures of adnexa, and the dermis; 3) within the epidermis, the epithelial structures of adnexa, and contiguous epithelia of other organs such as the genitourinary and gastrointestinal tracts. Our conclusions are that extramammary Paget's disease is more than one disease and in most instances begins in the epidermis as an adenocardinoma and extends from there into contiguous epithelium of hair follicles and eccrine sweat ducts. Uncommonly, Paget cells extend from the epidermis into the dermis and from there may metastasize. Rarely, extramammary Paget's disease results from direct extension into the skin of an adenocarcinoma in a contiguous organ such as the genitourinary or gastrointestinal tract.", "contents": "Extramammary Paget's disease. A critical reexamination. Fifty-five patients with extramammary Paget's disease were the source of material for this study. Step-sections were done through most of the specimens. Clinical information, including follow-up, was obtained on 45 of the 55 patients. Extramammary Paget's disease could be divided histologically according to where Paget cells were found, namely: 1) wholly within the epidermis and the epithelial structures of adnexa, and the dermis; 3) within the epidermis, the epithelial structures of adnexa, and contiguous epithelia of other organs such as the genitourinary and gastrointestinal tracts. Our conclusions are that extramammary Paget's disease is more than one disease and in most instances begins in the epidermis as an adenocardinoma and extends from there into contiguous epithelium of hair follicles and eccrine sweat ducts. Uncommonly, Paget cells extend from the epidermis into the dermis and from there may metastasize. Rarely, extramammary Paget's disease results from direct extension into the skin of an adenocarcinoma in a contiguous organ such as the genitourinary or gastrointestinal tract."}
{"id": "PMID:232974", "title": "[The use of bone scintigraphy with technetium 99 m pyrophosphates in the diagnosis of algodystrophies. A report on 74 observations (author's transl)].", "content": "Bone scintigraphy with technetium 99m pyrophosphates was used to study a series of 74 cases of algodystrophies. Though non-specific, this investigation was the determining factor for confirming the diagnosis in more than 48% of cases, by demonstrating early bone hyperfixation, its topographical characteristics, and the return to normal conditions after 3 to 12 months. Bone hyperfixation has to be exaluated together with clinical, biological, and radiological signs when considering the diagnosis, and though in half the cases it is not indispensable for diagnosis, it is always of value for determining the amount of extension of the algodystrophic process.", "contents": "[The use of bone scintigraphy with technetium 99 m pyrophosphates in the diagnosis of algodystrophies. A report on 74 observations (author's transl)]. Bone scintigraphy with technetium 99m pyrophosphates was used to study a series of 74 cases of algodystrophies. Though non-specific, this investigation was the determining factor for confirming the diagnosis in more than 48% of cases, by demonstrating early bone hyperfixation, its topographical characteristics, and the return to normal conditions after 3 to 12 months. Bone hyperfixation has to be exaluated together with clinical, biological, and radiological signs when considering the diagnosis, and though in half the cases it is not indispensable for diagnosis, it is always of value for determining the amount of extension of the algodystrophic process."}
{"id": "PMID:232977", "title": "Deficiency in the ability of serum from pigs on an atherogenic diet to stimulate the migration of 3T3 cells in culture.", "content": "The serum of pigs developing atherosclerosis is deficient in the ability to stimulate the migration of Balb/c-3T3-A31 cells in culture. This deficiency appears to be due to the presence of an inhibitor located in lipoprotein-free serum. The migration assay was used to follow the changing migration activity of the serum of pigs on a changing diet.", "contents": "Deficiency in the ability of serum from pigs on an atherogenic diet to stimulate the migration of 3T3 cells in culture. The serum of pigs developing atherosclerosis is deficient in the ability to stimulate the migration of Balb/c-3T3-A31 cells in culture. This deficiency appears to be due to the presence of an inhibitor located in lipoprotein-free serum. The migration assay was used to follow the changing migration activity of the serum of pigs on a changing diet."}
{"id": "PMID:232980", "title": "Size of lipoproteins in intestinal lympho of sheep and suckling lambs.", "content": "The relative importance of chylomicrons (Sf greater than 400) and very low density lipoproteins (Sf 20--400) in transporting lipids in lymph was investigated in surgically prepared adult sheep and pre-ruminant lambs fed low fat diets or infused intraduodenally with corn oil. The concentration of triacylglycerol in the intestinal lymph of sheep and lambs was increased from 520 and 925 mg/100 ml to 2326 and 2367 mg/100 ml respectively when corn oil was infused into the duodenum and the ratio of triacylglycerol to phospholipid changed from 3.7 and 5.5 to 9.5 and 9.7 respectively. The flow of lymph also increased. Electron microscopy and analytical and preparative ultracentrifugation showed that lymph lipoproteins from sheep and lambs fed low fat diets consisted mainly of lipoproteins 50 nm in diameter and that very low density lipoproteins (Sf 20--400) contirbuted up to 75% of the Sf greater than 20 lipoproteins. There were no lipoproteins with diameters above 150 nm. Infusion of corn oil into the duodenum of sheep and lambs increased the diameters of lymph lipoproteins. Most were 80--100 nm in diameter but substantial numbers above 150 and up to 400 mn were observed. The maximum contribution of very low density lipoproteins (Sf 20--400) to lipoproteins of Sf greater than 20 was 27--30%. The above findings demonstrate that the size of intestinal lymph lipoprotein particles increases with the amount of lipid absorbed from the small intestines and that the transport of lymph lipids, in ruminants, is similar to that previously found in rats, rabbits and man.", "contents": "Size of lipoproteins in intestinal lympho of sheep and suckling lambs. The relative importance of chylomicrons (Sf greater than 400) and very low density lipoproteins (Sf 20--400) in transporting lipids in lymph was investigated in surgically prepared adult sheep and pre-ruminant lambs fed low fat diets or infused intraduodenally with corn oil. The concentration of triacylglycerol in the intestinal lymph of sheep and lambs was increased from 520 and 925 mg/100 ml to 2326 and 2367 mg/100 ml respectively when corn oil was infused into the duodenum and the ratio of triacylglycerol to phospholipid changed from 3.7 and 5.5 to 9.5 and 9.7 respectively. The flow of lymph also increased. Electron microscopy and analytical and preparative ultracentrifugation showed that lymph lipoproteins from sheep and lambs fed low fat diets consisted mainly of lipoproteins 50 nm in diameter and that very low density lipoproteins (Sf 20--400) contirbuted up to 75% of the Sf greater than 20 lipoproteins. There were no lipoproteins with diameters above 150 nm. Infusion of corn oil into the duodenum of sheep and lambs increased the diameters of lymph lipoproteins. Most were 80--100 nm in diameter but substantial numbers above 150 and up to 400 mn were observed. The maximum contribution of very low density lipoproteins (Sf 20--400) to lipoproteins of Sf greater than 20 was 27--30%. The above findings demonstrate that the size of intestinal lymph lipoprotein particles increases with the amount of lipid absorbed from the small intestines and that the transport of lymph lipids, in ruminants, is similar to that previously found in rats, rabbits and man."}
{"id": "PMID:232981", "title": "Effect of intravenously infused dexamethasone on collagen metabolism in skin of merino sheep.", "content": "The effects of an 8-day intravenous infusion of dexamethasone (7.6 mg kg-0.75 body weight) on collagen biosynthesis and wool growth in skin were examined in four Merino wethers. Plasma dexamethasone concentrations reached their peaks during the first 24 h infusion, which were followed by relatively stable levels (c. 1 X 10(-7) M) for the next 4--5 days. Minor increases in plasma dexamethasone levels were recorded during the final 2 days of treatment. Dexamethasone concentrations quickly fell below the level of detection once infusion ceased. Marked decreases in the wet weight, thickness and protein content of skin were observed at the end of infusion. DNA content was reduced to 42.4 +/- 4.9% s.e.m. during the first 2 days of treatment, but in the next 4 days of infusion gradually increased to 85.0 +/0 12.5% of controls. The level of collagen (expressed as hydroxyproline content of its acid hydrolysate) was elevated throughout the infusion and then gradually declined in 3 weeks to about 60% of controls. The biosynthesis of collagen measured by the rate of [14C]hydroxyproline formation and the activity of proline, 2-oxoglutarate dioxygenase (EC 1.14.11.2. formerly prolyl hydroxylase) was reduced during the first half of treatment to a greater extent than the rate of [14C]proline incorporation into proteins. Wool growth was reduced by 80.4 +/- 11.6% in the post-infusion period which allowed three sheep out of four to be defleeced. Inhibition of collagen biosynthesis in sheep skin was due initially to a decrease in the activity of proline, 2-oxoglutarate dioxygenase and later to the reduced rate of proline incorporation into proteins. It was also evident that changes in biosynthetic rate of collagen were not reflected in the total level of skin collagen. The extent of wool growth depression in individual animals paralleled the changes in DNA content and the extent of collagen biosynthesis inhibition.", "contents": "Effect of intravenously infused dexamethasone on collagen metabolism in skin of merino sheep. The effects of an 8-day intravenous infusion of dexamethasone (7.6 mg kg-0.75 body weight) on collagen biosynthesis and wool growth in skin were examined in four Merino wethers. Plasma dexamethasone concentrations reached their peaks during the first 24 h infusion, which were followed by relatively stable levels (c. 1 X 10(-7) M) for the next 4--5 days. Minor increases in plasma dexamethasone levels were recorded during the final 2 days of treatment. Dexamethasone concentrations quickly fell below the level of detection once infusion ceased. Marked decreases in the wet weight, thickness and protein content of skin were observed at the end of infusion. DNA content was reduced to 42.4 +/- 4.9% s.e.m. during the first 2 days of treatment, but in the next 4 days of infusion gradually increased to 85.0 +/0 12.5% of controls. The level of collagen (expressed as hydroxyproline content of its acid hydrolysate) was elevated throughout the infusion and then gradually declined in 3 weeks to about 60% of controls. The biosynthesis of collagen measured by the rate of [14C]hydroxyproline formation and the activity of proline, 2-oxoglutarate dioxygenase (EC 1.14.11.2. formerly prolyl hydroxylase) was reduced during the first half of treatment to a greater extent than the rate of [14C]proline incorporation into proteins. Wool growth was reduced by 80.4 +/- 11.6% in the post-infusion period which allowed three sheep out of four to be defleeced. Inhibition of collagen biosynthesis in sheep skin was due initially to a decrease in the activity of proline, 2-oxoglutarate dioxygenase and later to the reduced rate of proline incorporation into proteins. It was also evident that changes in biosynthetic rate of collagen were not reflected in the total level of skin collagen. The extent of wool growth depression in individual animals paralleled the changes in DNA content and the extent of collagen biosynthesis inhibition."}
{"id": "PMID:232975", "title": "[Effect of silica on the anti-tumour activity of \"Corynebacterium parvum\" (author's transl)].", "content": "Silica, a specifically toxic substance for macrophages, has been used to study the role of these cells in the Corynebacterium parvum-induced anti-tumour protection. In the two experimental tumours studied, silica, C. parvum and tumour cells were injected by the same route: the intravenous route in the case of lymphosarcoma in XVII mice and the intraperitoneal in that of mammary carcinoma in C3H mice. The inhibition of the anti-tumour effect of C. parvum by the administration of silica was more pronounced in C3H than in XVII mice. Silica administration has only a weak and transient depressive effect on the stimulation of macrophage phagocytic activity induced by C. parvum. In addition, silica injection increased the adjuvant effect of C. parvum on the sheep red blood cell antibody response. These results suggest that the silica induced abrogation of the anti-tumour effect of C. parvum could be due to a local inhibition of macrophage stimulation at the tumour inoculation site.", "contents": "[Effect of silica on the anti-tumour activity of \"Corynebacterium parvum\" (author's transl)]. Silica, a specifically toxic substance for macrophages, has been used to study the role of these cells in the Corynebacterium parvum-induced anti-tumour protection. In the two experimental tumours studied, silica, C. parvum and tumour cells were injected by the same route: the intravenous route in the case of lymphosarcoma in XVII mice and the intraperitoneal in that of mammary carcinoma in C3H mice. The inhibition of the anti-tumour effect of C. parvum by the administration of silica was more pronounced in C3H than in XVII mice. Silica administration has only a weak and transient depressive effect on the stimulation of macrophage phagocytic activity induced by C. parvum. In addition, silica injection increased the adjuvant effect of C. parvum on the sheep red blood cell antibody response. These results suggest that the silica induced abrogation of the anti-tumour effect of C. parvum could be due to a local inhibition of macrophage stimulation at the tumour inoculation site."}
{"id": "PMID:232982", "title": "Gel electrophoresis of rotavirus RNA derived from six different animal species.", "content": "Rotavirus RNA prepared from calf, pig, mouse, deer, foal and dog-adapted human isolates was compared using polyacrylamide gel electrophoresis. Reproducible differences in the RNA migration patterns were found between all isolates. There were 11 clearly resolved segments in the pig, mouse and foal samples. The calf rotavirus RNA and deer rotavirus RNA separated into 9 bands and 10 bands, respectively. The dog-adapted human virus migrated in 12 bands, and this probably results from the complex passage history of the original human rotavirus isolate.", "contents": "Gel electrophoresis of rotavirus RNA derived from six different animal species. Rotavirus RNA prepared from calf, pig, mouse, deer, foal and dog-adapted human isolates was compared using polyacrylamide gel electrophoresis. Reproducible differences in the RNA migration patterns were found between all isolates. There were 11 clearly resolved segments in the pig, mouse and foal samples. The calf rotavirus RNA and deer rotavirus RNA separated into 9 bands and 10 bands, respectively. The dog-adapted human virus migrated in 12 bands, and this probably results from the complex passage history of the original human rotavirus isolate."}
{"id": "PMID:232976", "title": "[Entero-uterine fistual as the first symptom of intestinal neoplasms. Description of a case].", "content": "Vaginal elimination of stool due to sigmoid-uterine fistula was the first symptom in a case of neoplasia of the sigma. Few instances of a similar fistula appear in the literature. Bouskela, Ch\u00e9risi\u00e9, Yourde and Taieb observed one case starting from the uterus. McGregor & Bacon have described a fistula starting from the colon due to diverticulitis, as have Colceck & Staumann, Smalley et al., and Johnston & Stubbs. No previous example of tumour of the large intestine as the cause of a fistula with the corpus uteri could be found. On examination, the patient presented losss of stool via the vagina and a sigmoid-uterine fistula. Her condition was poor. Blood glucose was high, the protein picture was altered with a los of albumin, and infection was present. Radical management was impossible. Left colostomy reduce the causes of infection and permitted devitalisation of the fistula. Subjective and objective improvement followed, though further enlargement of the tumour engulfing the sigma and uterus led to death some months later due to the onset of renal block.", "contents": "[Entero-uterine fistual as the first symptom of intestinal neoplasms. Description of a case]. Vaginal elimination of stool due to sigmoid-uterine fistula was the first symptom in a case of neoplasia of the sigma. Few instances of a similar fistula appear in the literature. Bouskela, Ch\u00e9risi\u00e9, Yourde and Taieb observed one case starting from the uterus. McGregor & Bacon have described a fistula starting from the colon due to diverticulitis, as have Colceck & Staumann, Smalley et al., and Johnston & Stubbs. No previous example of tumour of the large intestine as the cause of a fistula with the corpus uteri could be found. On examination, the patient presented losss of stool via the vagina and a sigmoid-uterine fistula. Her condition was poor. Blood glucose was high, the protein picture was altered with a los of albumin, and infection was present. Radical management was impossible. Left colostomy reduce the causes of infection and permitted devitalisation of the fistula. Subjective and objective improvement followed, though further enlargement of the tumour engulfing the sigma and uterus led to death some months later due to the onset of renal block."}
{"id": "PMID:232983", "title": "Progressive muscular dystrophy type Duchenne. I. Spin label studies on the physico-chemical state of erythrocyte membranes.", "content": "Electron spin resonance studies of erythrocyte membranes from patients with Duchenne muscular dystrophy exhibit changes in the physical state of lipids and proteins in membranes when compared to membranes from normal subjects. The results suggest that the alterations in membrane lipid-protein organization are present in this disease.", "contents": "Progressive muscular dystrophy type Duchenne. I. Spin label studies on the physico-chemical state of erythrocyte membranes. Electron spin resonance studies of erythrocyte membranes from patients with Duchenne muscular dystrophy exhibit changes in the physical state of lipids and proteins in membranes when compared to membranes from normal subjects. The results suggest that the alterations in membrane lipid-protein organization are present in this disease."}
{"id": "PMID:232984", "title": "[Correlations between plasmatic alpha-tocopherol and lipids in male adults].", "content": "Plasma levels of alpha-tocopherol, beta-carotene, total lipid, total cholesterol, beta-lipoproteins, and triglyceride were measured in healthy italian male adults of various age groups. Alpha-tocopherol mean values varied from 0.96 mg/100 ml in the subjects of 18-24 years to 1,14 mg/100 ml in the subjects of 25-64 years and to 1,08 mg/100 ml in those above 55 years. No value lower than the generally accepted minimum of 0,5 mg/100 ml was found. Correlation coefficients of all the variables were also studied. Alpha-tocopherol was shown to be significantly related to age and plasma cholesterol. These data agree with other authors' results.", "contents": "[Correlations between plasmatic alpha-tocopherol and lipids in male adults]. Plasma levels of alpha-tocopherol, beta-carotene, total lipid, total cholesterol, beta-lipoproteins, and triglyceride were measured in healthy italian male adults of various age groups. Alpha-tocopherol mean values varied from 0.96 mg/100 ml in the subjects of 18-24 years to 1,14 mg/100 ml in the subjects of 25-64 years and to 1,08 mg/100 ml in those above 55 years. No value lower than the generally accepted minimum of 0,5 mg/100 ml was found. Correlation coefficients of all the variables were also studied. Alpha-tocopherol was shown to be significantly related to age and plasma cholesterol. These data agree with other authors' results."}
{"id": "PMID:232987", "title": "Interactions of neomycin with monomolecular films of polyphosphoinositides and other lipids.", "content": "The interactions of calcium and the aminoglycosidic antibiotic, neomycin, with various lipids were investigated in monomolecular films. Lipids were spread over a subphase of 0.05 M N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid, pH 7.0, and NaCl to give an ionic strength of 0.2. Measurements of surface pressure (pi) were taken with a Wilhelmy balance. In the absence of Ca2+, 1 muM--1 mM neomycin in the subphase decreased pi (i.e. condensed films) of all acidic lipids tested. In the presence of 1 mM Ca2+, neomycin did not change pi of films of phosphatidylserine, phosphatidylinositol and phosphatidic acid while it lowered pi of cardiolipin and cerebroside sulfate films. A unique pattern of interaction was observed with polyphosphoinositide monolayers. In the absence of Ca2+, 1 muM neomycin decreased pi followed by an increase of pi at higher neomycin concentrations. Ca2+ (1 mM) condensed the film significantly more than did neomycin. However, as little as 1 muM neomycin induced expansion of the calcium/lipid film which at 1 mM neomycin reached the same pi as in the absence of Ca2+. Such expansion was observed at all pressures of the film including the collapse pressure indicating a strong 'complex' between the drug and polyphosphoinositide not antagonized by Ca2+. In the absence of possible hydrophobic interactions, both the condensation and the expansion of the film should be mediated by ionic forces. Combined in vivo and in vitro evidence is discussed to suggest the polyphosphoinositides as the physiological receptors for aminoglycosides in the mammalian cell membrane.", "contents": "Interactions of neomycin with monomolecular films of polyphosphoinositides and other lipids. The interactions of calcium and the aminoglycosidic antibiotic, neomycin, with various lipids were investigated in monomolecular films. Lipids were spread over a subphase of 0.05 M N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid, pH 7.0, and NaCl to give an ionic strength of 0.2. Measurements of surface pressure (pi) were taken with a Wilhelmy balance. In the absence of Ca2+, 1 muM--1 mM neomycin in the subphase decreased pi (i.e. condensed films) of all acidic lipids tested. In the presence of 1 mM Ca2+, neomycin did not change pi of films of phosphatidylserine, phosphatidylinositol and phosphatidic acid while it lowered pi of cardiolipin and cerebroside sulfate films. A unique pattern of interaction was observed with polyphosphoinositide monolayers. In the absence of Ca2+, 1 muM neomycin decreased pi followed by an increase of pi at higher neomycin concentrations. Ca2+ (1 mM) condensed the film significantly more than did neomycin. However, as little as 1 muM neomycin induced expansion of the calcium/lipid film which at 1 mM neomycin reached the same pi as in the absence of Ca2+. Such expansion was observed at all pressures of the film including the collapse pressure indicating a strong 'complex' between the drug and polyphosphoinositide not antagonized by Ca2+. In the absence of possible hydrophobic interactions, both the condensation and the expansion of the film should be mediated by ionic forces. Combined in vivo and in vitro evidence is discussed to suggest the polyphosphoinositides as the physiological receptors for aminoglycosides in the mammalian cell membrane."}
{"id": "PMID:232988", "title": "Role of proteins and lipids in non-linear Arrhenius plots of Drosophila mitochondrial succinate-cytochrome c reductase studied by rebinding experiments.", "content": "Abrupt changes in the Arrhenius activation energy of membrane-bound enzymes have often been correlated with changes in the physical state of membrane phospholipids. Similar changes in activation energy have also been found in soluble enzymes. The possibility exists, therefore, that in some of the membrane-bound enzymes the changes might reflect intrinsic changes of the proteins independent of changes in the membrane phospholipids. This hypothesis was investigated using Drosophila mitochondria isolated from wild type and the mutant Ocd ts-1. In this mutant it has been shown that succinate-cytochrome c reductase exhibits a change in Arrhenius activation energy at 18 degrees C which is not found in the wild type (Sondergaard, L., Nielsen, N.C. and Smillie, R.M. (1975) FEBS lett. 50, 126-129). A quantitative thin-layer chromatographic analysis of mitochondrial phospholipids showed sphingomyelin to be more abundant in the wild type than in the mutant (5.2% and 4.3% of the total phospholipids, respectively). Since it was shown that the succinate-cytochrome c reductase had a lipid requirement for full activity, reciprocal rebinding experiments were done. These experiments showed that the reconstituted membranes exhibited the change in activation energy at 18 degrees C only when the protein moiety came from mutant mitochondria, that is, the change was independent of the source of the phospholipids used.", "contents": "Role of proteins and lipids in non-linear Arrhenius plots of Drosophila mitochondrial succinate-cytochrome c reductase studied by rebinding experiments. Abrupt changes in the Arrhenius activation energy of membrane-bound enzymes have often been correlated with changes in the physical state of membrane phospholipids. Similar changes in activation energy have also been found in soluble enzymes. The possibility exists, therefore, that in some of the membrane-bound enzymes the changes might reflect intrinsic changes of the proteins independent of changes in the membrane phospholipids. This hypothesis was investigated using Drosophila mitochondria isolated from wild type and the mutant Ocd ts-1. In this mutant it has been shown that succinate-cytochrome c reductase exhibits a change in Arrhenius activation energy at 18 degrees C which is not found in the wild type (Sondergaard, L., Nielsen, N.C. and Smillie, R.M. (1975) FEBS lett. 50, 126-129). A quantitative thin-layer chromatographic analysis of mitochondrial phospholipids showed sphingomyelin to be more abundant in the wild type than in the mutant (5.2% and 4.3% of the total phospholipids, respectively). Since it was shown that the succinate-cytochrome c reductase had a lipid requirement for full activity, reciprocal rebinding experiments were done. These experiments showed that the reconstituted membranes exhibited the change in activation energy at 18 degrees C only when the protein moiety came from mutant mitochondria, that is, the change was independent of the source of the phospholipids used."}
{"id": "PMID:232989", "title": "Exchange of phospholipids between unilamellar vesicles of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine and plasma very low density lipoproteins.", "content": "Purified phosphatidylcholine exchange protein from bovine liver was used to exchange [14C]dipalmitoyl phosphatidylcholine from sonicated vesicles to human plasma very low density lipoproteins (VLDL). The exchange of [14C]-dipalmitoyl phosphatidylcholine for VLDL phospholipids was temperature dependent and linear with respect to time and amount of exchange protein. In the absence of the exchange protein, less than 10% of the [14C]dipalmitoyl phosphatidylcholine was transferred. At an initial weight ratio of [14C]-dipalmitoyl phosphatidylcholine vesicles to VLDL phospholipid (1.2 mg) of 2.2, the exchange protein (14 microgram) replaced 55% of the VLDL phospholipids with [14C]dipalmitoyl phosphatidylcholine in 15 min; VLDL protein and cholesterol content were unaltered. From these studies we conclude that the exchange protein is a useful method to alter the phospholipid composition of VLDL under conditions such that there is minimal perturbation of the lipoprotein.", "contents": "Exchange of phospholipids between unilamellar vesicles of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine and plasma very low density lipoproteins. Purified phosphatidylcholine exchange protein from bovine liver was used to exchange [14C]dipalmitoyl phosphatidylcholine from sonicated vesicles to human plasma very low density lipoproteins (VLDL). The exchange of [14C]-dipalmitoyl phosphatidylcholine for VLDL phospholipids was temperature dependent and linear with respect to time and amount of exchange protein. In the absence of the exchange protein, less than 10% of the [14C]dipalmitoyl phosphatidylcholine was transferred. At an initial weight ratio of [14C]-dipalmitoyl phosphatidylcholine vesicles to VLDL phospholipid (1.2 mg) of 2.2, the exchange protein (14 microgram) replaced 55% of the VLDL phospholipids with [14C]dipalmitoyl phosphatidylcholine in 15 min; VLDL protein and cholesterol content were unaltered. From these studies we conclude that the exchange protein is a useful method to alter the phospholipid composition of VLDL under conditions such that there is minimal perturbation of the lipoprotein."}
{"id": "PMID:232990", "title": "A cyclic GMP-dependent histone kinase bound to liver nucleoli.", "content": "A method of steady-state electrophoresis in polyacrylamide gels was used to analyze the presence of cyclic nucleotide binding components in cell extracts. Multiple cyclic AMP and cyclic GMP binding components were detected in soluble cytoplasmic and nuclear extracts derived from avian liver, but only a single cyclic GMP binding protein was found in the 0.3 M NaCl extract of liver nucleoli. In the presence of cyclic GMP, this protein phosphorylated efficiently a calf thymus histone mixture and an endogenous nucleolar protein, which migrated identically with histone H4 in sodium dodecyl sulfate polyacrylamide gel electrophoresis. The isoelectric point of the cyclic GMP-binding protein was 4.8. Addition of cyclic GMP did not influence the activity of the endogenous nucleolar RNA polymerase.", "contents": "A cyclic GMP-dependent histone kinase bound to liver nucleoli. A method of steady-state electrophoresis in polyacrylamide gels was used to analyze the presence of cyclic nucleotide binding components in cell extracts. Multiple cyclic AMP and cyclic GMP binding components were detected in soluble cytoplasmic and nuclear extracts derived from avian liver, but only a single cyclic GMP binding protein was found in the 0.3 M NaCl extract of liver nucleoli. In the presence of cyclic GMP, this protein phosphorylated efficiently a calf thymus histone mixture and an endogenous nucleolar protein, which migrated identically with histone H4 in sodium dodecyl sulfate polyacrylamide gel electrophoresis. The isoelectric point of the cyclic GMP-binding protein was 4.8. Addition of cyclic GMP did not influence the activity of the endogenous nucleolar RNA polymerase."}
{"id": "PMID:232996", "title": "Electron spin resonance study of human alpha 1-acid glycoprotein interaction with a spin labelled steroid.", "content": "The interaction of human alpha 1-acid glycoprotein (AAG) with a corticosteroid was studied using nitroxide labeled deoxycorticosterone and electron spin resonance (ESR) spectroscopy. The ESR spectra of the spin labeled steroid in the presence of AAG could be used to characterize the ligand-protein interaction at equilibrium without the need of a separation between bound and free species. An association constant Ka of 6.10(5) M-1 at 20 degrees C and a binding capacity of one site per mole protein were found. ESR spectra recorded at equilibrium at various temperatures allowed the calculation of enthalpy and entropy variations for the steroid-protein interaction; these thermodynamic parameters exhibited a rapid change above 45 degrees C which may be related to a protein conformational modification above this temperature, as detected by circular dichroism study. The ESR spectra width could be used to define a polar character for the spin label environment in the steroid binding site of AAG and to calculate an apparent rotational correlation time of 2.8 x 10(-8) sec for the steroid-protein complex in aqueous solution at 20 degrees C. It can be concluded that spin labeling and ESR methodology is of value in the study of steroid-protein interactions of biological significance above all because it can provide direct physico-chemical information concerning the local environment of the ligand in its binding site at equilibrium.", "contents": "Electron spin resonance study of human alpha 1-acid glycoprotein interaction with a spin labelled steroid. The interaction of human alpha 1-acid glycoprotein (AAG) with a corticosteroid was studied using nitroxide labeled deoxycorticosterone and electron spin resonance (ESR) spectroscopy. The ESR spectra of the spin labeled steroid in the presence of AAG could be used to characterize the ligand-protein interaction at equilibrium without the need of a separation between bound and free species. An association constant Ka of 6.10(5) M-1 at 20 degrees C and a binding capacity of one site per mole protein were found. ESR spectra recorded at equilibrium at various temperatures allowed the calculation of enthalpy and entropy variations for the steroid-protein interaction; these thermodynamic parameters exhibited a rapid change above 45 degrees C which may be related to a protein conformational modification above this temperature, as detected by circular dichroism study. The ESR spectra width could be used to define a polar character for the spin label environment in the steroid binding site of AAG and to calculate an apparent rotational correlation time of 2.8 x 10(-8) sec for the steroid-protein complex in aqueous solution at 20 degrees C. It can be concluded that spin labeling and ESR methodology is of value in the study of steroid-protein interactions of biological significance above all because it can provide direct physico-chemical information concerning the local environment of the ligand in its binding site at equilibrium."}
{"id": "PMID:232993", "title": "Influence of light on activity of adenylate kinase and pterin-protein complexes from pea chloroplasts.", "content": "The activity of adenylate kinase (AK) and of pterin-protein complexes (PPC), whose proteins have adenylate kinase activity comparable to that of the enzyme was studied. It was established that light inhibits adenylate kinase activity and that this effect is partially eliminated by phosphate ions. The forward and reverse reactions catalyzed by AK and PPC were studied and it was found that the activity of native protein complexes is different in the forward and reverse reactions. The thermostable protein both of adenylate kinase and of the pterin-protein complexes had identical activity in the ADP dismutation and the reverse reaction.", "contents": "Influence of light on activity of adenylate kinase and pterin-protein complexes from pea chloroplasts. The activity of adenylate kinase (AK) and of pterin-protein complexes (PPC), whose proteins have adenylate kinase activity comparable to that of the enzyme was studied. It was established that light inhibits adenylate kinase activity and that this effect is partially eliminated by phosphate ions. The forward and reverse reactions catalyzed by AK and PPC were studied and it was found that the activity of native protein complexes is different in the forward and reverse reactions. The thermostable protein both of adenylate kinase and of the pterin-protein complexes had identical activity in the ADP dismutation and the reverse reaction."}
{"id": "PMID:232997", "title": "Kinetic and chemical properties of ATP sulphurylase from Penicillin chrysogenum.", "content": "Adenosine triphosphate sulphurylase (ATP: sulfate adenylyltransferase, EC 2.7.7.4.) has been purified from the filamentous fungus. Penicillium chrysogenum, and characterized physically, kinetically, and chemically. The P. Chrysogenum enzyme is an octomer (mol. wt. 440 000) composed of eight identical subunits (mol. wt. 55 000). Some physical constants are S20,w = 13.0 X 10(-13)s, D20,w = 2.94 X 10(-7) cm2 X s-1, v = 0.733 cm3 X g-1, A1%1cm = 8.71 at 278 nm. The enzyme catalyses (a) the synthesis of adenosine 5'-phosphosulphate (APS) and MgPPi from MgATP and SO2-4, (b) the hydrolysis of MgATP to AMP and MgPPi in the absence of SO2-4, (c) Mg32PPi-MgATP exchange in the absence of SO2-4, (d) molybdolysis of MgATP to AMP and MgPPi, (e) synthesis of MgATP and SO2-4 from APS and MgPPi, and (f) Mg32PPi-MgATP exchange in the presence of SO2-4. The Vmax values of reactions (a)-(c) are about 0.10-0.35 mumole X min-1 X mg enzyme-1. The Vmax values of reactions (d)-(f) are about 12-19 mumole X min-1 X mg enzyme-1. The catalytic activity of the enzyme in the direction of APS synthesis is rather low (0.13 unit X mg protein-1, corresponding to an active site turnover number of 7.15 min-1). However, the ATP sulphurylase content of mycelium growing on excess SO2-4 is 0.22 unit X g dry wt.-1, which is sufficient to account for the maximum in vivo rate of SO2-4 assimilation. The normal catalytic reaction is Ordered Bi Bi with A = MgATP, B = SO2-4, P = MgPPi, and Q = APS. Several lines of kinetic evidence suggest that the E.MgATP and E.APS complexes isomerize (to E approximately AMP.MgPPi and E approximately AMP.SO4, respectively) before the second substrate binds. Chemical modification studies have disclosed the presence of essential arginine, histidine, carboxyl, and tryosine residues. The latter is rather acidic (pKa = 7 or less). Nitration of the tyrosine increases the Km for MgATP without significantly affecting Kia for MgATP or Vmaxf. This result, and the fact that MgATP plus nitrate protects the enzyme against inactivation by tetranitromethane while MgATP alone does not, suggests that the essential tyrosine plays a role in nucleotide isomerization (perhaps as an adenylyl acceptor).", "contents": "Kinetic and chemical properties of ATP sulphurylase from Penicillin chrysogenum. Adenosine triphosphate sulphurylase (ATP: sulfate adenylyltransferase, EC 2.7.7.4.) has been purified from the filamentous fungus. Penicillium chrysogenum, and characterized physically, kinetically, and chemically. The P. Chrysogenum enzyme is an octomer (mol. wt. 440 000) composed of eight identical subunits (mol. wt. 55 000). Some physical constants are S20,w = 13.0 X 10(-13)s, D20,w = 2.94 X 10(-7) cm2 X s-1, v = 0.733 cm3 X g-1, A1%1cm = 8.71 at 278 nm. The enzyme catalyses (a) the synthesis of adenosine 5'-phosphosulphate (APS) and MgPPi from MgATP and SO2-4, (b) the hydrolysis of MgATP to AMP and MgPPi in the absence of SO2-4, (c) Mg32PPi-MgATP exchange in the absence of SO2-4, (d) molybdolysis of MgATP to AMP and MgPPi, (e) synthesis of MgATP and SO2-4 from APS and MgPPi, and (f) Mg32PPi-MgATP exchange in the presence of SO2-4. The Vmax values of reactions (a)-(c) are about 0.10-0.35 mumole X min-1 X mg enzyme-1. The Vmax values of reactions (d)-(f) are about 12-19 mumole X min-1 X mg enzyme-1. The catalytic activity of the enzyme in the direction of APS synthesis is rather low (0.13 unit X mg protein-1, corresponding to an active site turnover number of 7.15 min-1). However, the ATP sulphurylase content of mycelium growing on excess SO2-4 is 0.22 unit X g dry wt.-1, which is sufficient to account for the maximum in vivo rate of SO2-4 assimilation. The normal catalytic reaction is Ordered Bi Bi with A = MgATP, B = SO2-4, P = MgPPi, and Q = APS. Several lines of kinetic evidence suggest that the E.MgATP and E.APS complexes isomerize (to E approximately AMP.MgPPi and E approximately AMP.SO4, respectively) before the second substrate binds. Chemical modification studies have disclosed the presence of essential arginine, histidine, carboxyl, and tryosine residues. The latter is rather acidic (pKa = 7 or less). Nitration of the tyrosine increases the Km for MgATP without significantly affecting Kia for MgATP or Vmaxf. This result, and the fact that MgATP plus nitrate protects the enzyme against inactivation by tetranitromethane while MgATP alone does not, suggests that the essential tyrosine plays a role in nucleotide isomerization (perhaps as an adenylyl acceptor)."}
{"id": "PMID:232998", "title": "Oxidative phosphorylation linked to the dissimilatory reduction of elemental sulphur by Desulfovibrio.", "content": "Hydrogenase and cytochrome c3 purified from Desulfovibrio gigas and D. desulfuricans strain Norway form a soluble complex which is capable of transferring electrons from molecular hydrogen to colloidal sulphur (S0). In this reaction, sulphur is reduced to hydrogen sulphide. Since both strains are capable of growth using elemental sulphur as terminal electron acceptor, it was of interest to check for oxidative phosphorylation in this sulphur reduction sytem. Membranes isolated from D. gigas or D. desulfuricans strain Norway contain hydrogenase and c-type cytochromes and catalyse the H2 leads to S0 reaction. With D. gigas, esterification of orthophosphate is coupled to the membrane-mediated transfer of electrons from H2 to S0. A P/2e ratio of 0.1 was observed and this value could be reduced by the addition of colloidal sulphur with c2 may be more than a purely chemical reaction. Since whole cells can use sulphur flower while cell-free extracts react only with colloidal sulphur, it is evident that cells handle sulphur in a way which is not yet fully understood.", "contents": "Oxidative phosphorylation linked to the dissimilatory reduction of elemental sulphur by Desulfovibrio. Hydrogenase and cytochrome c3 purified from Desulfovibrio gigas and D. desulfuricans strain Norway form a soluble complex which is capable of transferring electrons from molecular hydrogen to colloidal sulphur (S0). In this reaction, sulphur is reduced to hydrogen sulphide. Since both strains are capable of growth using elemental sulphur as terminal electron acceptor, it was of interest to check for oxidative phosphorylation in this sulphur reduction sytem. Membranes isolated from D. gigas or D. desulfuricans strain Norway contain hydrogenase and c-type cytochromes and catalyse the H2 leads to S0 reaction. With D. gigas, esterification of orthophosphate is coupled to the membrane-mediated transfer of electrons from H2 to S0. A P/2e ratio of 0.1 was observed and this value could be reduced by the addition of colloidal sulphur with c2 may be more than a purely chemical reaction. Since whole cells can use sulphur flower while cell-free extracts react only with colloidal sulphur, it is evident that cells handle sulphur in a way which is not yet fully understood."}
{"id": "PMID:232994", "title": "Inhibition of adenine nucleotide transport in mitochondria of winter rye seedlings.", "content": "Inhibition of adenine nucleotide transport was studied in mitochondria of winter rye (Secale cereale) seedlings. It has been shown that plant mitochondria have a translocase similar to the adenine-nucleotide translocase of animal mitochondria, since atractyloside, at a concentration of 40 micro M, inhibits Chance's State 3 respiration 100%. It has been demonstrated that palmitoyl-CoA--formed by a mitochondrial system for activation of fatty acids--lowers the rate of State 3 respiration during succinate oxidation, if palmitate, CoA and ATP are introduced into the incubation medium simultaneously. This can be explained by an inhibition of transport of adenine nucleotides through the internal mitochondrial membrane. The inhibition in question is counteracted by addition of carnitine.", "contents": "Inhibition of adenine nucleotide transport in mitochondria of winter rye seedlings. Inhibition of adenine nucleotide transport was studied in mitochondria of winter rye (Secale cereale) seedlings. It has been shown that plant mitochondria have a translocase similar to the adenine-nucleotide translocase of animal mitochondria, since atractyloside, at a concentration of 40 micro M, inhibits Chance's State 3 respiration 100%. It has been demonstrated that palmitoyl-CoA--formed by a mitochondrial system for activation of fatty acids--lowers the rate of State 3 respiration during succinate oxidation, if palmitate, CoA and ATP are introduced into the incubation medium simultaneously. This can be explained by an inhibition of transport of adenine nucleotides through the internal mitochondrial membrane. The inhibition in question is counteracted by addition of carnitine."}
{"id": "PMID:233011", "title": "Effect of dietary supplementation of vitamin E on serum lipids and lipoproteins in rabbits fed a cholesterolemic diet.", "content": "The effect of dietary supplementation of vitamin E on serum cholsterol, triglycerides, lipoproteins and lipoprotein composition was studied in rabbits fed a one per cent cholesterol diet for a period of twelve weeks. Vitamin E supplemented animals were found to maintain significantly lower concentrations of serum cholesterol, triglycerides and very low density lipoproteins (d less than 1.006). The difference in the serum lipid content was mainly in the very low density lipoproteins of d less than 1.006. The possibility of an increased clearance of chylomicron remnants and decreased inhibition of extrahepatic lipoprotein lipase in hypercholesterolemic rabbits as a result of vitamin E supplementation is discussed in the light of the results obtained.", "contents": "Effect of dietary supplementation of vitamin E on serum lipids and lipoproteins in rabbits fed a cholesterolemic diet. The effect of dietary supplementation of vitamin E on serum cholsterol, triglycerides, lipoproteins and lipoprotein composition was studied in rabbits fed a one per cent cholesterol diet for a period of twelve weeks. Vitamin E supplemented animals were found to maintain significantly lower concentrations of serum cholesterol, triglycerides and very low density lipoproteins (d less than 1.006). The difference in the serum lipid content was mainly in the very low density lipoproteins of d less than 1.006. The possibility of an increased clearance of chylomicron remnants and decreased inhibition of extrahepatic lipoprotein lipase in hypercholesterolemic rabbits as a result of vitamin E supplementation is discussed in the light of the results obtained."}
{"id": "PMID:233012", "title": "Effect of dietary excess leucine on nicotinamide nucleotide level in rat liver.", "content": "1. Six groups of rats were freely fed diets containing casein at 5, 10 and 20% levels with and without nicotinic acid. After 2 weeks on these diets, hepatic nicotinamide nucleotide and free nicotinic acid concentrations were studied. 2. Hepatic nicotinamide nucleotide level was kept in the normal range in rats fed the 10 and 20% casein diets with and without nicotinic acid. 3. L-leucine supplemented at the 5% level to the 10 and 20% casein diets caused significant decrease in hepatic nicotinamide nucleotide level only in rats fed nicotinic acid devoid diet. 4. Hepatic nicotinamide nucleotide in rats fed the diet in which casein was replaced by zein increased significantly by adding nicotinic acid. This increase in the hepatic nicotinamide nucleotide caused by dietary supplemented nicotinic acid was not reduced by the addition of L-leucine. 5. The hepatic free nicotinic acid level did not change even in rats of which hepatic nicotinamide nucleotide was significantly reduced. 6. Urinary excretion of nicotinic acid and N-methylnicotinamide was increased significantly by adding nicotinic acid to the diet but was not affected by adding L-leucine at the 5% level. 7. From the above results, a possible mechanism of L-leucine action was discussed.", "contents": "Effect of dietary excess leucine on nicotinamide nucleotide level in rat liver. 1. Six groups of rats were freely fed diets containing casein at 5, 10 and 20% levels with and without nicotinic acid. After 2 weeks on these diets, hepatic nicotinamide nucleotide and free nicotinic acid concentrations were studied. 2. Hepatic nicotinamide nucleotide level was kept in the normal range in rats fed the 10 and 20% casein diets with and without nicotinic acid. 3. L-leucine supplemented at the 5% level to the 10 and 20% casein diets caused significant decrease in hepatic nicotinamide nucleotide level only in rats fed nicotinic acid devoid diet. 4. Hepatic nicotinamide nucleotide in rats fed the diet in which casein was replaced by zein increased significantly by adding nicotinic acid. This increase in the hepatic nicotinamide nucleotide caused by dietary supplemented nicotinic acid was not reduced by the addition of L-leucine. 5. The hepatic free nicotinic acid level did not change even in rats of which hepatic nicotinamide nucleotide was significantly reduced. 6. Urinary excretion of nicotinic acid and N-methylnicotinamide was increased significantly by adding nicotinic acid to the diet but was not affected by adding L-leucine at the 5% level. 7. From the above results, a possible mechanism of L-leucine action was discussed."}
{"id": "PMID:233013", "title": "Natural hypocholesterolemic agent: pectin plus ascorbic acid.", "content": "An addition of 5% citrus pectin and 0.5% ascorbic acid to high-fat diet of guinea pigs prevented total cholesterol accumulation in blood serum and the liver. Two groups of persons were given a preparation containing a daily dose of 15 g pectin and 450 mg ascorbic acid for 6 weeks. In 21 healthy persons with mild hypercholesterolemia total serum cholesterol dropped significantly by 24 mg/100 ml (8.6%), while the concentration of high density lipoprotein cholesterol remained unchanged. In 11 hyperlipemic outpatients (type IIa, IIb and IV) total serum cholesterol dropped by 68 mg/100 ml (18.7%). The changes in triglyceridemia proved inconsistent.", "contents": "Natural hypocholesterolemic agent: pectin plus ascorbic acid. An addition of 5% citrus pectin and 0.5% ascorbic acid to high-fat diet of guinea pigs prevented total cholesterol accumulation in blood serum and the liver. Two groups of persons were given a preparation containing a daily dose of 15 g pectin and 450 mg ascorbic acid for 6 weeks. In 21 healthy persons with mild hypercholesterolemia total serum cholesterol dropped significantly by 24 mg/100 ml (8.6%), while the concentration of high density lipoprotein cholesterol remained unchanged. In 11 hyperlipemic outpatients (type IIa, IIb and IV) total serum cholesterol dropped by 68 mg/100 ml (18.7%). The changes in triglyceridemia proved inconsistent."}
{"id": "PMID:233014", "title": "Serum lipids in swine fed large quantities of whey.", "content": "The causal relationship between hyperlipidemia and atherosclerotic diseases is undoubted. But studies of the last years have shown that this relationship is quite complex and may be even controversial. A food which has recently been placed in the foreground in lipid metabolism research is milk and its products. By accidental findings it was shown that the more milk was drunk, the lower the serum cholesterol concentration became. This brought about some controlled feeding studies on animals and humans. We chose swine for our feeding study because of their resemblance to human lipid metabolism. 57% of the whole energy consumed consisted of whey powder fed in a crossover study lasting 112 days. The results show that total cholesterol was significantly lower during whey feeding. The lipid decrease also included the HDL-fraction and, to a lesser degree, triglycerides. It seems well enough proved to be an accepted fact that the relative high content of saturated fatty aids in milk is cancelled by a substance present in milk and some of its products such as whey. Further investigations to study this milk factor in more detail including the application of high fat diets will be done.", "contents": "Serum lipids in swine fed large quantities of whey. The causal relationship between hyperlipidemia and atherosclerotic diseases is undoubted. But studies of the last years have shown that this relationship is quite complex and may be even controversial. A food which has recently been placed in the foreground in lipid metabolism research is milk and its products. By accidental findings it was shown that the more milk was drunk, the lower the serum cholesterol concentration became. This brought about some controlled feeding studies on animals and humans. We chose swine for our feeding study because of their resemblance to human lipid metabolism. 57% of the whole energy consumed consisted of whey powder fed in a crossover study lasting 112 days. The results show that total cholesterol was significantly lower during whey feeding. The lipid decrease also included the HDL-fraction and, to a lesser degree, triglycerides. It seems well enough proved to be an accepted fact that the relative high content of saturated fatty aids in milk is cancelled by a substance present in milk and some of its products such as whey. Further investigations to study this milk factor in more detail including the application of high fat diets will be done."}
{"id": "PMID:233017", "title": "Possibly electrotonically-mediated synaptic transmission: time-intensity trades in neurons in the superior olivary complex of cat.", "content": "Microelectrode studies were conducted on the probability of firing of neurons in the superior olivary complex of 11 anesthetized cats. Time-intensity trades were established for dichotic clicks. Inhibition was observed for interaural time differences in the region .05--4 msec. The authors point out that these extremely brief times render explanation difficult in terms of chemically-mediate synaptic transmission, and speculate that these results, while of an indirect nature, may be an expression of electrical synaptic transmission.", "contents": "Possibly electrotonically-mediated synaptic transmission: time-intensity trades in neurons in the superior olivary complex of cat. Microelectrode studies were conducted on the probability of firing of neurons in the superior olivary complex of 11 anesthetized cats. Time-intensity trades were established for dichotic clicks. Inhibition was observed for interaural time differences in the region .05--4 msec. The authors point out that these extremely brief times render explanation difficult in terms of chemically-mediate synaptic transmission, and speculate that these results, while of an indirect nature, may be an expression of electrical synaptic transmission."}
{"id": "PMID:233022", "title": "Studies on aminoglycoside antibiotics: enzymic mechanism of resistance and genetics.", "content": "The kanamycin inactivating enzyme, 3'-phosphotransferase and 6'-acetyltransferase were first found in 1967 and on the basis of the enzymic mechanism of resistance a new research approach to the development of active useful derivatives was explored. The enzymic mechanism of resistance was conclusively confirmed by the synthesis of 3'-deoxykanamycin A and 3',4'-dideoxykanamycin B which did not undergo inactivation by 3'-phosphotransferase and inhibited the growth of resistant strains. Besides APH(3') and AAC(6') described above, the following enzymes were found to be involved in the mechanism of resistance to aminoglycosides: APH(3''), APH(5''), APH(6), APH(2''), AAC(3), AAC(2'), AAD(3''), AAD(2''), AAD(4'), AAD(6). Not only the removal of the group which undergoes the enzyme reaction but also the modification of the group binding to the enzyme has also given active derivatives such as amikacin etc. The substrate specificity of the enzymes, enzymes in the immobilized state, and the application of proton and 13C nmr for structure determination of reaction products are reviewed. It was noticed that all enzymes involved in resistance contain adenosine- and aminoglycoside-binding sites. These enzymes were thus suggested to be mainly different primarily in the positional relationships between these binding sites. It suggests a close evolutionary relationships of these enzymes. The role of these enzymes in the biosynthesis of aminoglycoside antibiotics is discussed and a general mode of the biosynthesis of aminoglycosides is proposed: a gene or gene set involved in biosynthesis of 2-deoxystreptamine which has no cytotoxicity is widely distributed and the deoxystreptamine produced is transformed to the final products.", "contents": "Studies on aminoglycoside antibiotics: enzymic mechanism of resistance and genetics. The kanamycin inactivating enzyme, 3'-phosphotransferase and 6'-acetyltransferase were first found in 1967 and on the basis of the enzymic mechanism of resistance a new research approach to the development of active useful derivatives was explored. The enzymic mechanism of resistance was conclusively confirmed by the synthesis of 3'-deoxykanamycin A and 3',4'-dideoxykanamycin B which did not undergo inactivation by 3'-phosphotransferase and inhibited the growth of resistant strains. Besides APH(3') and AAC(6') described above, the following enzymes were found to be involved in the mechanism of resistance to aminoglycosides: APH(3''), APH(5''), APH(6), APH(2''), AAC(3), AAC(2'), AAD(3''), AAD(2''), AAD(4'), AAD(6). Not only the removal of the group which undergoes the enzyme reaction but also the modification of the group binding to the enzyme has also given active derivatives such as amikacin etc. The substrate specificity of the enzymes, enzymes in the immobilized state, and the application of proton and 13C nmr for structure determination of reaction products are reviewed. It was noticed that all enzymes involved in resistance contain adenosine- and aminoglycoside-binding sites. These enzymes were thus suggested to be mainly different primarily in the positional relationships between these binding sites. It suggests a close evolutionary relationships of these enzymes. The role of these enzymes in the biosynthesis of aminoglycoside antibiotics is discussed and a general mode of the biosynthesis of aminoglycosides is proposed: a gene or gene set involved in biosynthesis of 2-deoxystreptamine which has no cytotoxicity is widely distributed and the deoxystreptamine produced is transformed to the final products."}
{"id": "PMID:233024", "title": "Hormone-induced modification of EGF receptor proteolysis in the induction of EGF action.", "content": "A proposal that EGF action is mediated through enhanced internalization of EGF receptors is modified to account for more recent evidence. EGF receptors turn over at a rapid rate, and the maintenance of a steady state of EGF receptors on the cell surface is provided through a rapid synthesis of EGF receptors, balancing their removal. This rapid turnover of unoccupied receptors may arise through their internalization and proteolysis in the lysosomes, in much the same way as receptors are internalized and degraded when exposed to EGF, which enhances internalization. This provides a dilemmma for the endocytic activation concept, since slight enhancement of receptor internalization gives rise to a strong hormone response. This problem may be solved by the observation that EGF induces a change in its receptor, exposing an otherwise unavailable site for proteolytic cleavage. This hormone-dependent modification of receptors may be the critical step in the induction of responses to EGF and other hormones that are internalized with their receptors. Both platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) are shown to down-regulate EGF receptors, though transiently, placing still more stringent requirements on the specificity by which hormones might act through endocytic activation of their receptors.", "contents": "Hormone-induced modification of EGF receptor proteolysis in the induction of EGF action. A proposal that EGF action is mediated through enhanced internalization of EGF receptors is modified to account for more recent evidence. EGF receptors turn over at a rapid rate, and the maintenance of a steady state of EGF receptors on the cell surface is provided through a rapid synthesis of EGF receptors, balancing their removal. This rapid turnover of unoccupied receptors may arise through their internalization and proteolysis in the lysosomes, in much the same way as receptors are internalized and degraded when exposed to EGF, which enhances internalization. This provides a dilemmma for the endocytic activation concept, since slight enhancement of receptor internalization gives rise to a strong hormone response. This problem may be solved by the observation that EGF induces a change in its receptor, exposing an otherwise unavailable site for proteolytic cleavage. This hormone-dependent modification of receptors may be the critical step in the induction of responses to EGF and other hormones that are internalized with their receptors. Both platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) are shown to down-regulate EGF receptors, though transiently, placing still more stringent requirements on the specificity by which hormones might act through endocytic activation of their receptors."}
{"id": "PMID:233026", "title": "[Keratodermic genodermatosis with hydrocystomas, miliary cysts, xanthelasmas, nail and dental dystrophies, and basal cell epitheliomas].", "content": "Two cases of a condition including palms and soles keratoderma, ectodermal dysplasias and basal cell epitheliomas are reported by the authors, with clinical, genetical and pathological data. The condition is called Keratodermal Genodermatose with hydrocystomas, milium cysts, xanthelasma, dental and nail dysplasias and basal cell epitheliomata (Borda's syndrome).", "contents": "[Keratodermic genodermatosis with hydrocystomas, miliary cysts, xanthelasmas, nail and dental dystrophies, and basal cell epitheliomas]. Two cases of a condition including palms and soles keratoderma, ectodermal dysplasias and basal cell epitheliomas are reported by the authors, with clinical, genetical and pathological data. The condition is called Keratodermal Genodermatose with hydrocystomas, milium cysts, xanthelasma, dental and nail dysplasias and basal cell epitheliomata (Borda's syndrome)."}
{"id": "PMID:233028", "title": "[Cadmium content of vegetable foods in the effective range of a lead smelting plant].", "content": "In the effective range of a lead smelting plant, the repercussions of cadmium emissions (mainly past) on vegetables, fruit, soil and drinking water as well as of immissions were investigated by means of atomic absorption spectrometry. As compared to the \"normal\" cadmium level, the cadmium contents in vegetables and fruit were some 2- to 85-fold higher; and those in soils, some 70- to 230-fold. The mean contents in vegetables ranged from 0.4 to 25.5 p.p.m. (on a dry-weight basis); those in fruit, from 0.09 to 1.17 p.p.m. Cadmium concentrations varying from 6.8 to 22.8 p.p.m. were found in soil samples. The drinking water contained 0.009 p.p.m. of cadmium. The mean cadmium contents in the atmosphere and the sedimentary dust were 0.007 mg/m3 and 0.550 mg/m2/30d, respectively. In the territory investigated, the total human uptake of cadmium supplied by vegetables, fruit, potatoes, drinking water and air is 3.3-32.6 microgram/d. The following cadmium levels were found in human organ samples obtained at necropsy: right and left renal cortex, 33.99 and 35.98 p.p.m., respectively; liver, 3.14 p.p.m.; lungs, 0.63 p.p.m.; pancreas, 1.47 p.p.m.; brain stem, 0.16 p.p.m.", "contents": "[Cadmium content of vegetable foods in the effective range of a lead smelting plant]. In the effective range of a lead smelting plant, the repercussions of cadmium emissions (mainly past) on vegetables, fruit, soil and drinking water as well as of immissions were investigated by means of atomic absorption spectrometry. As compared to the \"normal\" cadmium level, the cadmium contents in vegetables and fruit were some 2- to 85-fold higher; and those in soils, some 70- to 230-fold. The mean contents in vegetables ranged from 0.4 to 25.5 p.p.m. (on a dry-weight basis); those in fruit, from 0.09 to 1.17 p.p.m. Cadmium concentrations varying from 6.8 to 22.8 p.p.m. were found in soil samples. The drinking water contained 0.009 p.p.m. of cadmium. The mean cadmium contents in the atmosphere and the sedimentary dust were 0.007 mg/m3 and 0.550 mg/m2/30d, respectively. In the territory investigated, the total human uptake of cadmium supplied by vegetables, fruit, potatoes, drinking water and air is 3.3-32.6 microgram/d. The following cadmium levels were found in human organ samples obtained at necropsy: right and left renal cortex, 33.99 and 35.98 p.p.m., respectively; liver, 3.14 p.p.m.; lungs, 0.63 p.p.m.; pancreas, 1.47 p.p.m.; brain stem, 0.16 p.p.m."}
{"id": "PMID:233033", "title": "On the molecular structure of some prostaglandin receptors.", "content": "Hypotheses are presented of the detailed molecular structure of two prostaglandin receptors both concerned in tumor-promotion processes. These structures have been derived by the comparison  of the molecular structure of agents active at the site with (i) a simple theoretical protein structure and (ii) the known x-ray structure of phospholipase A2. The first model receptor is stimulatory to the tumor-promotion process and may be located on the control system for ornithine decarboxylase. The binding of PG here is cooperative with the binding of Ca++. Naturally-occurring agonists at this receptor may include members of the cathartic class of drugs such as colocynth, chrysarobin, etc. Naturally-occurring antagonists at this site may include a number of anti-tumor compounds such as datiscoside. The second model receptor (PGE1) is inhibitory to the tumor-promotion process and is located at a specific allosteric site on the x-ray-determined structure of phospholipase A2. This site overlaps for one for lysolecithin (excitatory), for which tumor-promoting phorbol esters such as TPA are agonists and some anti-tumor drugs such as maytansine may be antagonists.", "contents": "On the molecular structure of some prostaglandin receptors. Hypotheses are presented of the detailed molecular structure of two prostaglandin receptors both concerned in tumor-promotion processes. These structures have been derived by the comparison  of the molecular structure of agents active at the site with (i) a simple theoretical protein structure and (ii) the known x-ray structure of phospholipase A2. The first model receptor is stimulatory to the tumor-promotion process and may be located on the control system for ornithine decarboxylase. The binding of PG here is cooperative with the binding of Ca++. Naturally-occurring agonists at this receptor may include members of the cathartic class of drugs such as colocynth, chrysarobin, etc. Naturally-occurring antagonists at this site may include a number of anti-tumor compounds such as datiscoside. The second model receptor (PGE1) is inhibitory to the tumor-promotion process and is located at a specific allosteric site on the x-ray-determined structure of phospholipase A2. This site overlaps for one for lysolecithin (excitatory), for which tumor-promoting phorbol esters such as TPA are agonists and some anti-tumor drugs such as maytansine may be antagonists."}
{"id": "PMID:233031", "title": "Decreased myocardial and renal content of 3',5'-AMP in genetically hypertensive rats: effects of PGE2 and PGF2 alpha.", "content": "Levels of c-AMP in heart and kidney of genetically hypertensive rats (SHR) were significantly lower than in normotensive Wistar animals. PGE2, 10 microgram/kg ip markedly increased the concentration of c-AMP in heart and kidney of SHR animals, but was without effect on this cyclic nucleotide content in normotensive controls. PGF2, in doses up to 100 microgram/kg, did not influence the concentrations of c-AMP in heart and kidney of SHR animals. Alterations in adenylate cyclase--c-AMP system in genetic hypertension are discussed.", "contents": "Decreased myocardial and renal content of 3',5'-AMP in genetically hypertensive rats: effects of PGE2 and PGF2 alpha. Levels of c-AMP in heart and kidney of genetically hypertensive rats (SHR) were significantly lower than in normotensive Wistar animals. PGE2, 10 microgram/kg ip markedly increased the concentration of c-AMP in heart and kidney of SHR animals, but was without effect on this cyclic nucleotide content in normotensive controls. PGF2, in doses up to 100 microgram/kg, did not influence the concentrations of c-AMP in heart and kidney of SHR animals. Alterations in adenylate cyclase--c-AMP system in genetic hypertension are discussed."}
{"id": "PMID:233035", "title": "9, 11-Azo-12-oxa-15-hydroxyprostanoic acid: a potent thromboxane synthetase inhibitor and a PGH2/TxA2 receptor antagonist.", "content": "9,11-Azo-13-oxa-15-hydroxyprostanoic acid (AOHP) is shown to be a potent inhibitor of thromboxane synthetase with an IC50 at about 10(-6)M. It also blocked the agonist actions of 9,11-epoxymethano-PGH2 (IC50 9 x 10(-7) M) and TxA2 (IC50 2.4 x 10(-6) M) on human platelet-rich plasma indicating that it also is a PGH2/TxA2 receptor blocker.", "contents": "9, 11-Azo-12-oxa-15-hydroxyprostanoic acid: a potent thromboxane synthetase inhibitor and a PGH2/TxA2 receptor antagonist. 9,11-Azo-13-oxa-15-hydroxyprostanoic acid (AOHP) is shown to be a potent inhibitor of thromboxane synthetase with an IC50 at about 10(-6)M. It also blocked the agonist actions of 9,11-epoxymethano-PGH2 (IC50 9 x 10(-7) M) and TxA2 (IC50 2.4 x 10(-6) M) on human platelet-rich plasma indicating that it also is a PGH2/TxA2 receptor blocker."}
{"id": "PMID:233036", "title": "PGI2 and PGD2 effects on cyclic AMP and human T-cell mitogenesis.", "content": "The effects of PGI2, PGD2, and PGF2 alpha on human peripheral blood lymphocytes (HPBL) cyclic AMP levels and their response to a T cell mitogen (PHA) were investigated. It was determined that although PGI2, PGD2, and PGE2 all elevate intracellular levels of cyclic AMP in HPBL, only PGD2 and PGE2 exert potent suppression of PHA-induced lymphocyte proliferation. It is suggested that the instability of PGI2 in aqueous solution is at least partially responsible for its relative inability to maintain elevated levels of cyclic AMP and concomitant suppression of mitogenesis. PGD2 was found to exert an effect very similar to PGE2, both in terms of cyclic AMP elevation and suppression of T cell mitogenesis.", "contents": "PGI2 and PGD2 effects on cyclic AMP and human T-cell mitogenesis. The effects of PGI2, PGD2, and PGF2 alpha on human peripheral blood lymphocytes (HPBL) cyclic AMP levels and their response to a T cell mitogen (PHA) were investigated. It was determined that although PGI2, PGD2, and PGE2 all elevate intracellular levels of cyclic AMP in HPBL, only PGD2 and PGE2 exert potent suppression of PHA-induced lymphocyte proliferation. It is suggested that the instability of PGI2 in aqueous solution is at least partially responsible for its relative inability to maintain elevated levels of cyclic AMP and concomitant suppression of mitogenesis. PGD2 was found to exert an effect very similar to PGE2, both in terms of cyclic AMP elevation and suppression of T cell mitogenesis."}
{"id": "PMID:233030", "title": "Metabolism of cyclic 3',5'-AMP injected into the rat brain lateral ventricle.", "content": "(14C)-cAMP was injected into the lateral ventricle of the rat brain and autoradiographic studies and assay of metabolism of this nucleotide were carried out. (14C)-cAMP rapidly penetrates into the cerebrospinal fluid in other brain ventricles and into the subarachnoidol cerebellar space. 14C was also present in the brain tissue adjacent to the lumen of the ventricles. Given intraventricularly (14C)-cAMP is rapidly metabolized and the presence of 14C in the brain tissue is probably the consequence of the incorporation of metabolites of (14C)-cAMP.", "contents": "Metabolism of cyclic 3',5'-AMP injected into the rat brain lateral ventricle. (14C)-cAMP was injected into the lateral ventricle of the rat brain and autoradiographic studies and assay of metabolism of this nucleotide were carried out. (14C)-cAMP rapidly penetrates into the cerebrospinal fluid in other brain ventricles and into the subarachnoidol cerebellar space. 14C was also present in the brain tissue adjacent to the lumen of the ventricles. Given intraventricularly (14C)-cAMP is rapidly metabolized and the presence of 14C in the brain tissue is probably the consequence of the incorporation of metabolites of (14C)-cAMP."}
{"id": "PMID:233037", "title": "[Ochronotic arthropathy. A case report: radiographic and scintigraphic comparative  study (author's transl)].", "content": "After description of etiopathogenetic, anatomopathological and clinical aspects of the disease, the authors relate about a case of ochronotic arthropathy, lining on its typical radiological patterns. Scintigraphic study with 99mTc-pertechnetate and with 99mTc-pyrophosphate, excluding any phlogistic component, agree with dysmetabolic and degenerative nature of this arthropathy.", "contents": "[Ochronotic arthropathy. A case report: radiographic and scintigraphic comparative  study (author's transl)]. After description of etiopathogenetic, anatomopathological and clinical aspects of the disease, the authors relate about a case of ochronotic arthropathy, lining on its typical radiological patterns. Scintigraphic study with 99mTc-pertechnetate and with 99mTc-pyrophosphate, excluding any phlogistic component, agree with dysmetabolic and degenerative nature of this arthropathy."}
{"id": "PMID:233038", "title": "[Seroepidemiological study of Herpes simplex virus type 2 in adult women of Costa Rica].", "content": "The frequency of genital Herpes simplex type 2 infections in a group of twenty adult Costa Rican women was studied by isolation of the virus and the measurement of neutralizing antibody activity in sera. The virus could not be isolated in any of the vaginal secretions. Neutralizing antibody activity to herpes virus types 1 and 2 was found in sera from sixteen subjects. An antibody II/I index equal to or larger than 87, indicative of infection with Herpes simplex type 2 was found in fifty per cent of the population studied, a second segment was composed by the subjects with indices below 87. Evaluation of antibody activity to Herpes simplex type 2 revealed that: a) only a small percentage of the women lacked detectable antibody activity to the virus; b) there is a significant difference (p < 0.005) between the mean number of years of sexual experience among the two population segments; and c) there is a positive correlation (p < 0.05) between II/I index values and age among the women of the population segment with a II/I index equal to or larger than 87.", "contents": "[Seroepidemiological study of Herpes simplex virus type 2 in adult women of Costa Rica]. The frequency of genital Herpes simplex type 2 infections in a group of twenty adult Costa Rican women was studied by isolation of the virus and the measurement of neutralizing antibody activity in sera. The virus could not be isolated in any of the vaginal secretions. Neutralizing antibody activity to herpes virus types 1 and 2 was found in sera from sixteen subjects. An antibody II/I index equal to or larger than 87, indicative of infection with Herpes simplex type 2 was found in fifty per cent of the population studied, a second segment was composed by the subjects with indices below 87. Evaluation of antibody activity to Herpes simplex type 2 revealed that: a) only a small percentage of the women lacked detectable antibody activity to the virus; b) there is a significant difference (p < 0.005) between the mean number of years of sexual experience among the two population segments; and c) there is a positive correlation (p < 0.05) between II/I index values and age among the women of the population segment with a II/I index equal to or larger than 87."}
{"id": "PMID:233039", "title": "Histochemistry of the post-resuscitation changes in the brain.", "content": "In 20 dogs, acid mucopolysaccharides, gangliosides, lysosomal enzymes and iontransport enzymes were investigated. Material was taken 2, 24 and 72 h after 15 min of clinical death due to electrotrauma. Changes in the post-resuscitation period indicated deterioration of transmembrane ion--metabolite transport in the brain. These changes had phasic variations that reflect the complexity of post-resuscitation processes.", "contents": "Histochemistry of the post-resuscitation changes in the brain. In 20 dogs, acid mucopolysaccharides, gangliosides, lysosomal enzymes and iontransport enzymes were investigated. Material was taken 2, 24 and 72 h after 15 min of clinical death due to electrotrauma. Changes in the post-resuscitation period indicated deterioration of transmembrane ion--metabolite transport in the brain. These changes had phasic variations that reflect the complexity of post-resuscitation processes."}
{"id": "PMID:233044", "title": "Effects of ascorbate on leucocytes: Part I. Effects of ascorbate on neutrophil motility and intracellular cyclic nucleotide levels in vitro.", "content": "A preliminary series of experiments indicated that ascorbic acid and calcium and sodium ascorbate in the absence of serum had no stimulatory effect on neutrophil motility. However, when neutrophils were pre-incubated with ascorbate at concentrations between 5 X 10(-2)M and 1 X 10(-1)M in the presence of fresh normal autologous serum (5% final concentration) considerable stimulation of random motility and migration towards the leuco-attractants C5a and casein was observed. The serum factor required for ascorbate-mediated enhanced locomotion was heat unstable and was probably not serum albumin since no stimulation of cell migration was observed when serum was replaced with varying amounts of human serum albumin. Calcium ascorbate was the most potent stimulant of neutrophil motility. Concentrations of calcium and sodium ascorbate which increased migration promoted elevation of intracellular cyclic guanosine monophosphate (cGMP) levels, but not of adenosine monophosphate (cAMP). These same concentrations also caused increased glyclytic activity. It is suggested that the enhanced neutrophil motility mediated by ascorbic acid and calcium and sodium ascorbate in the presence of serum may be due to increased cGMP and/or glycolysis.", "contents": "Effects of ascorbate on leucocytes: Part I. Effects of ascorbate on neutrophil motility and intracellular cyclic nucleotide levels in vitro. A preliminary series of experiments indicated that ascorbic acid and calcium and sodium ascorbate in the absence of serum had no stimulatory effect on neutrophil motility. However, when neutrophils were pre-incubated with ascorbate at concentrations between 5 X 10(-2)M and 1 X 10(-1)M in the presence of fresh normal autologous serum (5% final concentration) considerable stimulation of random motility and migration towards the leuco-attractants C5a and casein was observed. The serum factor required for ascorbate-mediated enhanced locomotion was heat unstable and was probably not serum albumin since no stimulation of cell migration was observed when serum was replaced with varying amounts of human serum albumin. Calcium ascorbate was the most potent stimulant of neutrophil motility. Concentrations of calcium and sodium ascorbate which increased migration promoted elevation of intracellular cyclic guanosine monophosphate (cGMP) levels, but not of adenosine monophosphate (cAMP). These same concentrations also caused increased glyclytic activity. It is suggested that the enhanced neutrophil motility mediated by ascorbic acid and calcium and sodium ascorbate in the presence of serum may be due to increased cGMP and/or glycolysis."}
{"id": "PMID:233045", "title": "Community participation in cardiac rehabilitation.", "content": "Cardiac patients are not solely responsible for their own rehabilitation. The rehabilitative process is a prolonged one, and success lies in multidisciplinary management involving the patient, the immediate family and the community. The Health Act (Act No. 63 of 1977) has various implications for the future provision of rehabilitative services in South Africa. Each member of the health team and the community has a specific role to play, either within or outside the hospital setting, thus providing ongoing rehabilitative supervision of cardiac patients.", "contents": "Community participation in cardiac rehabilitation. Cardiac patients are not solely responsible for their own rehabilitation. The rehabilitative process is a prolonged one, and success lies in multidisciplinary management involving the patient, the immediate family and the community. The Health Act (Act No. 63 of 1977) has various implications for the future provision of rehabilitative services in South Africa. Each member of the health team and the community has a specific role to play, either within or outside the hospital setting, thus providing ongoing rehabilitative supervision of cardiac patients."}
{"id": "PMID:233046", "title": "The heart in diabetes mellitus. Part I. Biochemical basis for myocardial dysfunction.", "content": "The heart in acutely diabetic animals is subject to multiple inhibitions of glucose metabolism caused by enhanced metabolism of free fatty acids (FFA) and ketone bodies. Such metabolic changes may impair the reaction of the diabetic heart to oxygen lack. In chronically diabetic hearts the increased deposition of triglycerides in the heart and the formation of glycoproteins may underlie the newly recognized clinical entity of diabetic cardiomyopathy.", "contents": "The heart in diabetes mellitus. Part I. Biochemical basis for myocardial dysfunction. The heart in acutely diabetic animals is subject to multiple inhibitions of glucose metabolism caused by enhanced metabolism of free fatty acids (FFA) and ketone bodies. Such metabolic changes may impair the reaction of the diabetic heart to oxygen lack. In chronically diabetic hearts the increased deposition of triglycerides in the heart and the formation of glycoproteins may underlie the newly recognized clinical entity of diabetic cardiomyopathy."}
{"id": "PMID:233043", "title": "[A case of peripheral neuropathy in an acromegalic subject. Pathogenetic considerations].", "content": "A case of acromegaly with peripheral neuropathy characterized by acroparaesthesiae in the median nerve field of both sides is presented. Electrophysiological examination shows bilateral slowing of the motor conduction velocity of the median nerve through the carpal tunnel. The possible pathogenetic mechanisms of the peripheral neuropathy in acromegalic are discussed in the light of the most recent theories about the GH action. Suggestions are made that some associated hormonal disorders diabetes, hyperaldosteronism, hyperthyroidism) can play some part in the neuropathy pathogenesis.", "contents": "[A case of peripheral neuropathy in an acromegalic subject. Pathogenetic considerations]. A case of acromegaly with peripheral neuropathy characterized by acroparaesthesiae in the median nerve field of both sides is presented. Electrophysiological examination shows bilateral slowing of the motor conduction velocity of the median nerve through the carpal tunnel. The possible pathogenetic mechanisms of the peripheral neuropathy in acromegalic are discussed in the light of the most recent theories about the GH action. Suggestions are made that some associated hormonal disorders diabetes, hyperaldosteronism, hyperthyroidism) can play some part in the neuropathy pathogenesis."}
{"id": "PMID:233047", "title": "Serum high-density lipoprotein cholesterol, glucose tolerance and other variables in obese black adolescent girls.", "content": "Obesity is very common in South Africal Black girls aged 18 - 20 years. Severely obese White women have greatly reduced values for serum high-density lipoprotein (HDL) cholesterol. In a series of Black girls studied in rural and urban areas, mean values for HDL cholesterol were not significantly different in the obese compared with the non-obese groups. There were also no significant differences between obese and non-obese groups in mean serum cholesterol, triglyceride, uric acid, and blood glucose at fasting and 1 hour after a glucose drink. The same finding prevailed regarding blood pressures. All values for blood components were biologically more favourable in Black than in White adolescent girls (reported values). Mean sugar intakes of the obese were not significantly lower. Evidently, the metabolic and other disabilities linked with obesity in young White women have no counterpart in obese Black adolescent girls.", "contents": "Serum high-density lipoprotein cholesterol, glucose tolerance and other variables in obese black adolescent girls. Obesity is very common in South Africal Black girls aged 18 - 20 years. Severely obese White women have greatly reduced values for serum high-density lipoprotein (HDL) cholesterol. In a series of Black girls studied in rural and urban areas, mean values for HDL cholesterol were not significantly different in the obese compared with the non-obese groups. There were also no significant differences between obese and non-obese groups in mean serum cholesterol, triglyceride, uric acid, and blood glucose at fasting and 1 hour after a glucose drink. The same finding prevailed regarding blood pressures. All values for blood components were biologically more favourable in Black than in White adolescent girls (reported values). Mean sugar intakes of the obese were not significantly lower. Evidently, the metabolic and other disabilities linked with obesity in young White women have no counterpart in obese Black adolescent girls."}
{"id": "PMID:233051", "title": "Hepatitis B surface antigen and hepatocellular carcinoma in Southern Africa.", "content": "Most series in Africa show a high percentage of hepatitis B surface antigen in hepatocellular carcinoma. Two groups of cases were investigated in this study. The one was derived from the autopsy material at Baragwanath hospital from subjects who had lived in Soweto, a large Black urban town. The second group consisted of male Black mineworkers generally originating from rural areas. A combination of the aldehydefuchsin stain and immunoperoxidase technique was used. The two groups showed totally different results. The Baragwanath series consisted of 24 hepatocellular carcinomas of which only 4 (17%) were HBsAg positive. Of the 24 cases, 14 had cirrhosis of which 9 were macronodular and 5 micronodular. Ten of these cases showed heavy iron overload. The series of male Black mineworkers comprised 22 cases of which 16 (72%) were HBsAg positive. Twelve of the 22 cases showed a macronodular cirrhosis and there were no micronodular cirrhoses. Only one case showed severe iron overload. These findings delineate two different populations of hepatocellular carcinoma in Southern Africa.", "contents": "Hepatitis B surface antigen and hepatocellular carcinoma in Southern Africa. Most series in Africa show a high percentage of hepatitis B surface antigen in hepatocellular carcinoma. Two groups of cases were investigated in this study. The one was derived from the autopsy material at Baragwanath hospital from subjects who had lived in Soweto, a large Black urban town. The second group consisted of male Black mineworkers generally originating from rural areas. A combination of the aldehydefuchsin stain and immunoperoxidase technique was used. The two groups showed totally different results. The Baragwanath series consisted of 24 hepatocellular carcinomas of which only 4 (17%) were HBsAg positive. Of the 24 cases, 14 had cirrhosis of which 9 were macronodular and 5 micronodular. Ten of these cases showed heavy iron overload. The series of male Black mineworkers comprised 22 cases of which 16 (72%) were HBsAg positive. Twelve of the 22 cases showed a macronodular cirrhosis and there were no micronodular cirrhoses. Only one case showed severe iron overload. These findings delineate two different populations of hepatocellular carcinoma in Southern Africa."}
{"id": "PMID:233052", "title": "Sclerosing angioma of the lung. Case report and electron microscope investigation.", "content": "Electron microscopy of a sclerosing angioma of the lung, a coincidental finding in the upper lobe of a 32-year-old woman. The rare, benign tumor, whose vascular proliferation by light microscopy is reminiscent of an angioma, exhibits a clear epithelial structure by electron microscopy. The tumor may develop out of immature pneumocytes. The paper discusses histogenesis and problems of differential diagnosis (potential confusion with carcinomas).", "contents": "Sclerosing angioma of the lung. Case report and electron microscope investigation. Electron microscopy of a sclerosing angioma of the lung, a coincidental finding in the upper lobe of a 32-year-old woman. The rare, benign tumor, whose vascular proliferation by light microscopy is reminiscent of an angioma, exhibits a clear epithelial structure by electron microscopy. The tumor may develop out of immature pneumocytes. The paper discusses histogenesis and problems of differential diagnosis (potential confusion with carcinomas)."}
{"id": "PMID:233057", "title": "[Pre- and postoperative eye findings in hypophyseal adenoma].", "content": "When hypophyseal tumours are present, eye symptoms are the leading signs; they indicate, however, an advanced tumour stage. On the basis of 274 histologically verified hypophyseal adenomas, pre- and postoperative ophthalmological findings were analysed. Disturbances of the visual acuity were found preoperatively in 85.4 per cent, scotomas in 86.1 per cent and an optical nerve atrophy in 67.2 per cent of the patients. After neurosurgical intervention, 41.8 per cent of the examined patients showed an improvement of the visual acuity and 59.2 per cent a regression of the scotomas. Optical nerve atrophy was found in 78.1 per cent which was a higher percentage than before the operation. Disturbances of the visual acuity or scotomas that have persisted for a prolonged period of time show, just as optical nerve atrophy, a more unfavourable prognosis. So it had to be the aim of a neurosurgical treatment to diagnose the pituitary adenoma at an early time in order to improve the chances of a success. Eosinophilic hypophyseal adenomas are more easily recognisable, because of acromegalia being present in almost all cases. Ophthalmologically, they show less scotomas since they reach the dimensions of the chromophobic or mixed type adenomas only rarely. When blindness has developed, the situation is very serious since only in exceptional cases a recovery of sight is possible.", "contents": "[Pre- and postoperative eye findings in hypophyseal adenoma]. When hypophyseal tumours are present, eye symptoms are the leading signs; they indicate, however, an advanced tumour stage. On the basis of 274 histologically verified hypophyseal adenomas, pre- and postoperative ophthalmological findings were analysed. Disturbances of the visual acuity were found preoperatively in 85.4 per cent, scotomas in 86.1 per cent and an optical nerve atrophy in 67.2 per cent of the patients. After neurosurgical intervention, 41.8 per cent of the examined patients showed an improvement of the visual acuity and 59.2 per cent a regression of the scotomas. Optical nerve atrophy was found in 78.1 per cent which was a higher percentage than before the operation. Disturbances of the visual acuity or scotomas that have persisted for a prolonged period of time show, just as optical nerve atrophy, a more unfavourable prognosis. So it had to be the aim of a neurosurgical treatment to diagnose the pituitary adenoma at an early time in order to improve the chances of a success. Eosinophilic hypophyseal adenomas are more easily recognisable, because of acromegalia being present in almost all cases. Ophthalmologically, they show less scotomas since they reach the dimensions of the chromophobic or mixed type adenomas only rarely. When blindness has developed, the situation is very serious since only in exceptional cases a recovery of sight is possible."}
{"id": "PMID:233058", "title": "Detection and changes of nucleotide pyrophosphotransferase activity of Streptomyces griseus strains in submerged culture.", "content": "Nucleotide pyrophosphotransferase (NPT) activity of two Streptomyces griseus strains was studied in submerged culture during their life cycle. NPT activity could be detected only in the culture filtrate but not in the membrane fraction or in cell extract of the sporulating (streptomycin-non-producing) S. griseus No. 45-H. No enzyme could be detected in the non-sporulating (streptomycin-producing) S. griseus No 52--1 cultures.", "contents": "Detection and changes of nucleotide pyrophosphotransferase activity of Streptomyces griseus strains in submerged culture. Nucleotide pyrophosphotransferase (NPT) activity of two Streptomyces griseus strains was studied in submerged culture during their life cycle. NPT activity could be detected only in the culture filtrate but not in the membrane fraction or in cell extract of the sporulating (streptomycin-non-producing) S. griseus No. 45-H. No enzyme could be detected in the non-sporulating (streptomycin-producing) S. griseus No 52--1 cultures."}
{"id": "PMID:233063", "title": "[Inhibiting effect of low density lipoproteins (LDL) on neutrophil function (author's transl)].", "content": "LDL preparations obtained from normal individuals of known genetic type have been added to neutrophils from healthy donors. After incubation at 37 degrees C for 30 min, and washing in Hank's solution, in order to evaluate metabolic and bactericidal activities neutrophils were assayed by the nitroblue tetrazolium (NBT) quantitative test, using latex particles, and by E. coli killing test. LDL in aliquots of 100-500 microgram/2 x 10(6) neutrophils, inhibited NBT reduction and reduced neutrophil killing of E. coli by more than 50%. No difference was observed in the degree of inhibition using LDL and neutrophils obtained from donors of either the same or of different Ag phenotype. These data suggest that the immunoregulatory activity of LDL affects lymphocyte as well as neutrophil function.", "contents": "[Inhibiting effect of low density lipoproteins (LDL) on neutrophil function (author's transl)]. LDL preparations obtained from normal individuals of known genetic type have been added to neutrophils from healthy donors. After incubation at 37 degrees C for 30 min, and washing in Hank's solution, in order to evaluate metabolic and bactericidal activities neutrophils were assayed by the nitroblue tetrazolium (NBT) quantitative test, using latex particles, and by E. coli killing test. LDL in aliquots of 100-500 microgram/2 x 10(6) neutrophils, inhibited NBT reduction and reduced neutrophil killing of E. coli by more than 50%. No difference was observed in the degree of inhibition using LDL and neutrophils obtained from donors of either the same or of different Ag phenotype. These data suggest that the immunoregulatory activity of LDL affects lymphocyte as well as neutrophil function."}
{"id": "PMID:233068", "title": "Na+/K+-dependent adenosinetriphosphatase in rabbit kidney. Separation by affinity chromatography.", "content": "We attempted separations by affinity chromatography of the Na+/K+-dependent adenosinetriphosphatase, using Sepharose 6B covalently coupled with ouabain, either on microsomal fractions or on preparations purified by discontinuous sucrose density gradient ultracentrifugation. The material, specifically eluted with ouabain, was tested to evaluate the recovery of ATPase activity and ouabain binding capacity. The results have shown the efficiency of this technique for (Na+/K+)-APTase isolation.", "contents": "Na+/K+-dependent adenosinetriphosphatase in rabbit kidney. Separation by affinity chromatography. We attempted separations by affinity chromatography of the Na+/K+-dependent adenosinetriphosphatase, using Sepharose 6B covalently coupled with ouabain, either on microsomal fractions or on preparations purified by discontinuous sucrose density gradient ultracentrifugation. The material, specifically eluted with ouabain, was tested to evaluate the recovery of ATPase activity and ouabain binding capacity. The results have shown the efficiency of this technique for (Na+/K+)-APTase isolation."}
{"id": "PMID:233064", "title": "[Neurovegetative regulation of gastrin secretion].", "content": "The literature is reviewed in an account of the part played by the adrenergic and cholinergic systems in the regulation of gastrin secretion. As matters now stand, it can be said that, whereas the adrenergic system is capable of activating such secretion, the cholinergic system appears to be capable of modulating it by inhibition rather than stimulation. While it can be agreed that mediation of the adrenergic function occurs via the beta receptors, the possibility that the alpha receptors may also be responsible under certain conditions cannot be ruled out.", "contents": "[Neurovegetative regulation of gastrin secretion]. The literature is reviewed in an account of the part played by the adrenergic and cholinergic systems in the regulation of gastrin secretion. As matters now stand, it can be said that, whereas the adrenergic system is capable of activating such secretion, the cholinergic system appears to be capable of modulating it by inhibition rather than stimulation. While it can be agreed that mediation of the adrenergic function occurs via the beta receptors, the possibility that the alpha receptors may also be responsible under certain conditions cannot be ruled out."}
{"id": "PMID:233069", "title": "[In-vitro evaluation of morphine dependence. I. Response of the rat \"fundus\" to ACh].", "content": "The kinetic of cholinergic receptor systems was studied in an in vitro model for opiate tolerance and dependence. The fundus strip of rats chronically treated with morphine and sacrificed at different time intervals and in different conditions (with and without abstinence signs) was used. In evaluating the responses of fundus to ACh, the cholinergic receptor system showed the same response both in a condition of abstinence and in a condition of non-abstinence in vivo and in vitro. The response does vary however, according to the duration of the treatment: after an initial increase it comes back to its normal values, thus reproducing the tolerance pattern.", "contents": "[In-vitro evaluation of morphine dependence. I. Response of the rat \"fundus\" to ACh]. The kinetic of cholinergic receptor systems was studied in an in vitro model for opiate tolerance and dependence. The fundus strip of rats chronically treated with morphine and sacrificed at different time intervals and in different conditions (with and without abstinence signs) was used. In evaluating the responses of fundus to ACh, the cholinergic receptor system showed the same response both in a condition of abstinence and in a condition of non-abstinence in vivo and in vitro. The response does vary however, according to the duration of the treatment: after an initial increase it comes back to its normal values, thus reproducing the tolerance pattern."}
{"id": "PMID:233070", "title": "[Effect of chlorpropamide and of phenformin on isolated liver plasmatic membranes].", "content": "Previous observations from this laboratory suggest that chlorpropamide and phenformin, two hypoglycemic drugs belonging to sulfonylureas and biguanides respectively, act on liver plasma membranes altering the activity of enzymes bound to plasma membrane as (Na+-K+)-ATPase. This enzyme, an integral membrane protein which shows a cooperative behavior, has been used as an allosteric probe able to give information on plasma membrane. Our experiments show that (Na+-K+)-ATPase has a positive cooperative behaviour, as suggested from Hill coefficient n > l. The two hypoglycemic drugs decrease the Hill coefficient; in addition both chlorpropamide and phenformin inhibit (Na+-K+)-dependent but not Mg2+-dependent ATPase activity.", "contents": "[Effect of chlorpropamide and of phenformin on isolated liver plasmatic membranes]. Previous observations from this laboratory suggest that chlorpropamide and phenformin, two hypoglycemic drugs belonging to sulfonylureas and biguanides respectively, act on liver plasma membranes altering the activity of enzymes bound to plasma membrane as (Na+-K+)-ATPase. This enzyme, an integral membrane protein which shows a cooperative behavior, has been used as an allosteric probe able to give information on plasma membrane. Our experiments show that (Na+-K+)-ATPase has a positive cooperative behaviour, as suggested from Hill coefficient n > l. The two hypoglycemic drugs decrease the Hill coefficient; in addition both chlorpropamide and phenformin inhibit (Na+-K+)-dependent but not Mg2+-dependent ATPase activity."}
{"id": "PMID:233071", "title": "Relationship between thiamin phosphorylation and intestinal transport in vitro: effect of chloroethylthiamin.", "content": "The effect of Chloroethylthiamin (CET), a structural analog of thiamin, on thiamin pyrophosphokinase (TPKase) activity of the supernatant of rat isolated enterocytes was compared with that on thiamin intestinal transport by rat everted jejunal sacs. Thiamin- thiazol-2(14C) was used as a substrate both for TPKase activity and for thiamin serosal transport and uptake. CET strongly inhibited TPKase activity of isolated enterocytes: at molar concentrations 10 or 100 times higher than labeled thiamin, the inhibition was 57 and 100% respectively. The inhibition was of the competitive type, with a Ki = 15 microM. At a molar concentration 10 times higher than labeled thiamin, CET lowered the thiamin serosal transport by 60%, and the sac wall content of free and phosphorylated thiamin by 54 and 42% respectively. At the 1:10 thiamin: CET molar ratio, the extent of the reductions of TPKase activity (57%) and of phosphorylated thiamin content of intestinal sac walls (42%) were of the same order. This indicates a relationship between the two events. Moreover, since TPKase activity inhibition alone resulted in the lowering of labeled thiamin serosal transport, thiamin phosphorylation and transport are probably two strictly related processes.", "contents": "Relationship between thiamin phosphorylation and intestinal transport in vitro: effect of chloroethylthiamin. The effect of Chloroethylthiamin (CET), a structural analog of thiamin, on thiamin pyrophosphokinase (TPKase) activity of the supernatant of rat isolated enterocytes was compared with that on thiamin intestinal transport by rat everted jejunal sacs. Thiamin- thiazol-2(14C) was used as a substrate both for TPKase activity and for thiamin serosal transport and uptake. CET strongly inhibited TPKase activity of isolated enterocytes: at molar concentrations 10 or 100 times higher than labeled thiamin, the inhibition was 57 and 100% respectively. The inhibition was of the competitive type, with a Ki = 15 microM. At a molar concentration 10 times higher than labeled thiamin, CET lowered the thiamin serosal transport by 60%, and the sac wall content of free and phosphorylated thiamin by 54 and 42% respectively. At the 1:10 thiamin: CET molar ratio, the extent of the reductions of TPKase activity (57%) and of phosphorylated thiamin content of intestinal sac walls (42%) were of the same order. This indicates a relationship between the two events. Moreover, since TPKase activity inhibition alone resulted in the lowering of labeled thiamin serosal transport, thiamin phosphorylation and transport are probably two strictly related processes."}
{"id": "PMID:233072", "title": "Molecular mechanism of general anesthesia: II. Spin label studies on synaptic membranes.", "content": "In this communication we report the effects of general anesthetics on the mobility and order of spin labeled stearic acid derivatives in synaptic membranes and in bilayers formed from the lipids extracted therefrom. The anesthetics studied abolish the immobilization induced by synaptic membrane proteins on the membrane lipids : this effect, observed particularly in the bilayer core, is interpreted as a labilization of lipid-protein interactions induced by anesthetics.", "contents": "Molecular mechanism of general anesthesia: II. Spin label studies on synaptic membranes. In this communication we report the effects of general anesthetics on the mobility and order of spin labeled stearic acid derivatives in synaptic membranes and in bilayers formed from the lipids extracted therefrom. The anesthetics studied abolish the immobilization induced by synaptic membrane proteins on the membrane lipids : this effect, observed particularly in the bilayer core, is interpreted as a labilization of lipid-protein interactions induced by anesthetics."}
{"id": "PMID:233076", "title": "Cerebellar malformations: some pathogenetic considerations.", "content": "1) Destructive processes are responsible for most cases of cerebellar microgyria of the trabecular pattern. Erosion and subsequent fusion of the folia produce the disorganized pattern in which the various cellular elements retain their noraml relationship and are capable of normal maturation. Intrauterine infection is responsible for most cases; the evidence is conclusive in some cases, presumptive in others. 2) Faulty genetic coding, as illustrated by the trisomies, may lead to formation of heterotopias. The primitive cells aggregating around the dentate nucleus should be interpreted as matrix cells and not as cells of the external granular layer. Cortical heterotopias with attempted internal organisation also occur; their origin is obscure. The unusual, possibly unique, transposition of the internal granular and Purkinje cell layers observed in one case may be ascribed to faulty formation of the Bergmann glia by analogy with the weaver mouse. 3) It is impossible at present to disentangle the role of genetic and environmental factors in the pathogenesis of the hysraphic malformations. It is possible, however, that defective fusion of the intraventricular cerebellar primordium plays a part in the development of the Dandy-Walker malformation, of midine cerebellar clefts in some cases of occipital encephalocele, and of extra-axial ependymal cysts of the posterior fossa.", "contents": "Cerebellar malformations: some pathogenetic considerations. 1) Destructive processes are responsible for most cases of cerebellar microgyria of the trabecular pattern. Erosion and subsequent fusion of the folia produce the disorganized pattern in which the various cellular elements retain their noraml relationship and are capable of normal maturation. Intrauterine infection is responsible for most cases; the evidence is conclusive in some cases, presumptive in others. 2) Faulty genetic coding, as illustrated by the trisomies, may lead to formation of heterotopias. The primitive cells aggregating around the dentate nucleus should be interpreted as matrix cells and not as cells of the external granular layer. Cortical heterotopias with attempted internal organisation also occur; their origin is obscure. The unusual, possibly unique, transposition of the internal granular and Purkinje cell layers observed in one case may be ascribed to faulty formation of the Bergmann glia by analogy with the weaver mouse. 3) It is impossible at present to disentangle the role of genetic and environmental factors in the pathogenesis of the hysraphic malformations. It is possible, however, that defective fusion of the intraventricular cerebellar primordium plays a part in the development of the Dandy-Walker malformation, of midine cerebellar clefts in some cases of occipital encephalocele, and of extra-axial ependymal cysts of the posterior fossa."}
{"id": "PMID:233077", "title": "Hypoglycaemia secondary to pancreatic islet cell adenoma.", "content": "The detailed case histories of 5 patients with hypoglycaemic episodes secondary to islet cell adenoma of the pancreas are presented. Clinical recognition of this syndrome remains the major problem but a full and detailed medical history is usually strongly suggestive of the correct diagnosis. The clinical diagnosis is confirmed by the repeated demonstrated that: 1) Symptomatic episodes produced by fasting are in fact due to hypoglycaemia (plasma glucose level less than 2.5 mmol/litre) 2) Such episodes are relieved by glucose administration 3) Concomitant hyperinsulinaemia is present (serum insulin greater than 8 micro-units/ml in the fasting state). Surgical resection of the adenoma produces a complete cure but the identification of the lesion at operation may be difficult and preoperative means of accurate localisation may be needed.", "contents": "Hypoglycaemia secondary to pancreatic islet cell adenoma. The detailed case histories of 5 patients with hypoglycaemic episodes secondary to islet cell adenoma of the pancreas are presented. Clinical recognition of this syndrome remains the major problem but a full and detailed medical history is usually strongly suggestive of the correct diagnosis. The clinical diagnosis is confirmed by the repeated demonstrated that: 1) Symptomatic episodes produced by fasting are in fact due to hypoglycaemia (plasma glucose level less than 2.5 mmol/litre) 2) Such episodes are relieved by glucose administration 3) Concomitant hyperinsulinaemia is present (serum insulin greater than 8 micro-units/ml in the fasting state). Surgical resection of the adenoma produces a complete cure but the identification of the lesion at operation may be difficult and preoperative means of accurate localisation may be needed."}
{"id": "PMID:233073", "title": "Adrenal reactivity to ACTH age changes in silver foxes inheriting different defensive behaviors.", "content": "We have studied the influence of selection for behavior in female silver foxes upon their adrenal reactivity to ACTH. It has been found that in the first year of life, in females from a population selected for domesticated behavior (tame), there is no differentiated adrenal response to different doses of ACTH. In wild females during the first year of life, varying strength of adrenal response to large and small doses of ACTH is noted. During the second year of life, the differential adrenal response to different doses of ACTH is improved in females of both behavioral groups; the reactivity of tame second-year females to small doses of corticotrophin surpasses that of wild second-year animals. It is concluded that during ontogeny in domesticated silver fox females there is a retardation in the establishment of an adequate response to ACTH by the adrenals, as compared to nondomesticated females.", "contents": "Adrenal reactivity to ACTH age changes in silver foxes inheriting different defensive behaviors. We have studied the influence of selection for behavior in female silver foxes upon their adrenal reactivity to ACTH. It has been found that in the first year of life, in females from a population selected for domesticated behavior (tame), there is no differentiated adrenal response to different doses of ACTH. In wild females during the first year of life, varying strength of adrenal response to large and small doses of ACTH is noted. During the second year of life, the differential adrenal response to different doses of ACTH is improved in females of both behavioral groups; the reactivity of tame second-year females to small doses of corticotrophin surpasses that of wild second-year animals. It is concluded that during ontogeny in domesticated silver fox females there is a retardation in the establishment of an adequate response to ACTH by the adrenals, as compared to nondomesticated females."}
{"id": "PMID:233078", "title": "Motor fibre refractory period and motor conduction velocity range.", "content": "The absolute and relative motor refractory periods and the range of motor conduction velocity were investigated in 25 normal subjects and in 25 patients suffering from peripheral neuropathy. The refractory periods were examined by a collision method, which eliminates the effect of the first of the paired stimuli, thus allowing the effect of the second stimulus to be clearly recorded. The range of conduction velocity was also examined by a collision method, and the conduction times were corrected by subtracting the absolute and relative refractory periods from the figures given by this method. The maximum motor conduction velocities obtained with this technique closely corresponded with those found using conventional methods. The results show that the refactory periods are prolonged and the conduction velocities are reduced in peripheral neuropathies, especially of segmental demyelination type, but the range of conduction velocity is not necessarily increased. The failure to suppress fully the effect of the proximal stimulus by a distal stimulus is a phenomenon found in peripheral neuropathies.", "contents": "Motor fibre refractory period and motor conduction velocity range. The absolute and relative motor refractory periods and the range of motor conduction velocity were investigated in 25 normal subjects and in 25 patients suffering from peripheral neuropathy. The refractory periods were examined by a collision method, which eliminates the effect of the first of the paired stimuli, thus allowing the effect of the second stimulus to be clearly recorded. The range of conduction velocity was also examined by a collision method, and the conduction times were corrected by subtracting the absolute and relative refractory periods from the figures given by this method. The maximum motor conduction velocities obtained with this technique closely corresponded with those found using conventional methods. The results show that the refactory periods are prolonged and the conduction velocities are reduced in peripheral neuropathies, especially of segmental demyelination type, but the range of conduction velocity is not necessarily increased. The failure to suppress fully the effect of the proximal stimulus by a distal stimulus is a phenomenon found in peripheral neuropathies."}
{"id": "PMID:233079", "title": "Effect of tetrahydrocannabinol and ethidium bromide on DNA metabolism and embryogenesis in Volvox.", "content": "The effects of delta 9-tetrahydrocannabinol (THC) and ethidium bromide (EB) on the developmental life cycle and DNA metabolism of Volvox carteri have been investigated. THC, previously shown to interfere specifically with cytoplasmic DNA (cDNA) in this organism, was used at different concentrations and at different times during the life cycle. The morphological consequences observed were found to be dependent on the nature and time of treatment. This study also indicates that ethidium bromide induces degradatin of cDNA similar to that mediated by THC. However, unlike THC, it also causes the cessation of nuclear DNA synthesis. The consequences of EB treatment on morphological development are different from those observed with THC. A correlatin of these observations with the biochemical results presented suggests possible models in which the amounts and proportions of nuclear and cytoplasmic DNA play a role in the regulation of embryogenesis in this organism.", "contents": "Effect of tetrahydrocannabinol and ethidium bromide on DNA metabolism and embryogenesis in Volvox. The effects of delta 9-tetrahydrocannabinol (THC) and ethidium bromide (EB) on the developmental life cycle and DNA metabolism of Volvox carteri have been investigated. THC, previously shown to interfere specifically with cytoplasmic DNA (cDNA) in this organism, was used at different concentrations and at different times during the life cycle. The morphological consequences observed were found to be dependent on the nature and time of treatment. This study also indicates that ethidium bromide induces degradatin of cDNA similar to that mediated by THC. However, unlike THC, it also causes the cessation of nuclear DNA synthesis. The consequences of EB treatment on morphological development are different from those observed with THC. A correlatin of these observations with the biochemical results presented suggests possible models in which the amounts and proportions of nuclear and cytoplasmic DNA play a role in the regulation of embryogenesis in this organism."}
{"id": "PMID:233081", "title": "[Allergy due to castor bean meal (author's transl)].", "content": "A comprehensive review of the literature on allergy due to castor bean is given as it occurs by inhalation of dust particles in the environment of milk working with castor bean. Furthermore it may occur by handling of castor bean and of its expressed residuals after oil production. A case report is presented about a respiratory allergy caused by castor bean meal containing fertilizer used in culturing grass plats. Symptomes of increased dyspnoe following repeated exposures and a strongly positive skin test to an extract of castor bean have been observed. There is strong evidence that the castor bean has a high allergenic potency, requiring attention in allergy tests.", "contents": "[Allergy due to castor bean meal (author's transl)]. A comprehensive review of the literature on allergy due to castor bean is given as it occurs by inhalation of dust particles in the environment of milk working with castor bean. Furthermore it may occur by handling of castor bean and of its expressed residuals after oil production. A case report is presented about a respiratory allergy caused by castor bean meal containing fertilizer used in culturing grass plats. Symptomes of increased dyspnoe following repeated exposures and a strongly positive skin test to an extract of castor bean have been observed. There is strong evidence that the castor bean has a high allergenic potency, requiring attention in allergy tests."}
{"id": "PMID:233087", "title": "The effects of levamisole on some functions of mouse macrophages after in vitro and in vivo administration.", "content": "In vitro incubation of peritoneal macrophages from normal, peptone-stimulated mice with levamisole (1-100 microM) for 1 and 22 h had no effect on either phagocytosis of particulate material (sheep erythrocytes, zymosan) or cellular levels and release of lysosomal enzymes (beta-D-glucuronidase, cathepsin D). By contrast, levamisole 1 and 5 mM dramatically increased enzyme release while inhibiting phagocytosis. In some experiments, however, these high concentrations of levamisole caused an elevated cell mortality. When incubation was extended to 72 h, a decrease of both phagocytosis and enzyme release was observed. The catabolism of endocytosed antigens (sheep erythrocytes, human gammaglobulin) was not at all or only slightly modified depending upon the antigen. The cellular level of cyclic AMP remained unchanged in all experiments. In vivo exposure of macrophages to levamisole (2.5 and 10 mg/kg/day i.p. for 3 days) produced a dose-dependent increase in processing of endocytosed antigens as shown by an enhanced transfer of initially endocytosed material to the macrophage plasma membrane. The other parameters were not modified. The immunogenicity of erythrocytes, when endocytosed by levamisole-treated macrophages and transferred into unsensitized recipients, was increased in some in vivo experiments.", "contents": "The effects of levamisole on some functions of mouse macrophages after in vitro and in vivo administration. In vitro incubation of peritoneal macrophages from normal, peptone-stimulated mice with levamisole (1-100 microM) for 1 and 22 h had no effect on either phagocytosis of particulate material (sheep erythrocytes, zymosan) or cellular levels and release of lysosomal enzymes (beta-D-glucuronidase, cathepsin D). By contrast, levamisole 1 and 5 mM dramatically increased enzyme release while inhibiting phagocytosis. In some experiments, however, these high concentrations of levamisole caused an elevated cell mortality. When incubation was extended to 72 h, a decrease of both phagocytosis and enzyme release was observed. The catabolism of endocytosed antigens (sheep erythrocytes, human gammaglobulin) was not at all or only slightly modified depending upon the antigen. The cellular level of cyclic AMP remained unchanged in all experiments. In vivo exposure of macrophages to levamisole (2.5 and 10 mg/kg/day i.p. for 3 days) produced a dose-dependent increase in processing of endocytosed antigens as shown by an enhanced transfer of initially endocytosed material to the macrophage plasma membrane. The other parameters were not modified. The immunogenicity of erythrocytes, when endocytosed by levamisole-treated macrophages and transferred into unsensitized recipients, was increased in some in vivo experiments."}
{"id": "PMID:233085", "title": "Inhibition of human peptidyl dipeptidase (angiotensin I converting enzyme: kininase II) by human serum albumin and its fragments.", "content": "Purified peptidyl dipeptidase (angiotensin I converting enzyme or kininase II) from human lung or hog kidney is inhibited by commercially prepared plasma protein preparations, by human serum albumin and by the additive albumin stabilizer, acetyltryptophan. After the initial steps of purification, albumin was detected by immunodiffusion as a component in human lung peptidyl dipeptidase preparation. Fragment C of albumin (sequence 124-298) is a more potent inhibitor than the parent molecule (Ki = 1.7 X 10(-5)M). Reduction and carboxymethylation of five of the six S-S bridges in Fragment C yield the most potent noncompetitive inhibitor (Ki = 3 X 10(-6)M). Reduction of the sixth bridge raises the K1. This indicates that maintenance of the tertiary structure in Fragment C is of importance for the inhibition. Neither albumin nor Fragment C are substrates of the enzyme. Fragment C and its derivative also inhibit the inactivation of bradykinin by the purified human enzyme and by the peptidyl dipeptidase on the surface of intact cultured human endothelial cells.", "contents": "Inhibition of human peptidyl dipeptidase (angiotensin I converting enzyme: kininase II) by human serum albumin and its fragments. Purified peptidyl dipeptidase (angiotensin I converting enzyme or kininase II) from human lung or hog kidney is inhibited by commercially prepared plasma protein preparations, by human serum albumin and by the additive albumin stabilizer, acetyltryptophan. After the initial steps of purification, albumin was detected by immunodiffusion as a component in human lung peptidyl dipeptidase preparation. Fragment C of albumin (sequence 124-298) is a more potent inhibitor than the parent molecule (Ki = 1.7 X 10(-5)M). Reduction and carboxymethylation of five of the six S-S bridges in Fragment C yield the most potent noncompetitive inhibitor (Ki = 3 X 10(-6)M). Reduction of the sixth bridge raises the K1. This indicates that maintenance of the tertiary structure in Fragment C is of importance for the inhibition. Neither albumin nor Fragment C are substrates of the enzyme. Fragment C and its derivative also inhibit the inactivation of bradykinin by the purified human enzyme and by the peptidyl dipeptidase on the surface of intact cultured human endothelial cells."}
{"id": "PMID:233101", "title": "Retroperitoneal lymph node dissection for Wilms' tumor.", "content": "Nephrectomy for Wilms' tumor was performed on 58 patients over a 20-yr period, and retroperitoneal lymphadenectomy was performed on 35 who presented with no demonstrable metastases. The survival rate was 100% for 19 clinical group I patients with negative nodes. Positive nodes in 9 instances led to 5 long-term survivors and significantly influenced staging as a guide for further therapy.", "contents": "Retroperitoneal lymph node dissection for Wilms' tumor. Nephrectomy for Wilms' tumor was performed on 58 patients over a 20-yr period, and retroperitoneal lymphadenectomy was performed on 35 who presented with no demonstrable metastases. The survival rate was 100% for 19 clinical group I patients with negative nodes. Positive nodes in 9 instances led to 5 long-term survivors and significantly influenced staging as a guide for further therapy."}
{"id": "PMID:233102", "title": "Nonvisualization of the intravenous pyelogram--a poor prognostic sign in Wilms' tumor?", "content": "In a series of 49 consecutive cases of Wilms' tumor from a single institution, there was a 20% incidence of nonvisualization on the initial intravenous pyelogram. Even though nonvisualization was secondary to either gross or microscopic invasion of the renal vein or renal pelvis, this did not forecast a grim progosis. Seven of the nine patients with nonvisualization are presently alive and tumor-free at least 5 yr after resection. The only two deaths in this particular group were unrelated to the Wilms' tumor.", "contents": "Nonvisualization of the intravenous pyelogram--a poor prognostic sign in Wilms' tumor? In a series of 49 consecutive cases of Wilms' tumor from a single institution, there was a 20% incidence of nonvisualization on the initial intravenous pyelogram. Even though nonvisualization was secondary to either gross or microscopic invasion of the renal vein or renal pelvis, this did not forecast a grim progosis. Seven of the nine patients with nonvisualization are presently alive and tumor-free at least 5 yr after resection. The only two deaths in this particular group were unrelated to the Wilms' tumor."}
{"id": "PMID:233103", "title": "Postradiation renovascular hypertension.", "content": "Radiation injury to arteries can represent a significant complication of therapeutic irradiation, even when the dosage used has not been excessive as judged by approved protocols. Children in whom therapeutic abdominal irradiation has been used should be monitored indefinitely for the development of hypertension. The presence of hypertension in such children with normal blood urea nitrogen (BUN) and creatinine, and without proteinuria, should prompt investigation for a renovascular lesion. Standard bypass procedures are usually effective, although the long-term success may be compromised by continuing changes in affected vessels.", "contents": "Postradiation renovascular hypertension. Radiation injury to arteries can represent a significant complication of therapeutic irradiation, even when the dosage used has not been excessive as judged by approved protocols. Children in whom therapeutic abdominal irradiation has been used should be monitored indefinitely for the development of hypertension. The presence of hypertension in such children with normal blood urea nitrogen (BUN) and creatinine, and without proteinuria, should prompt investigation for a renovascular lesion. Standard bypass procedures are usually effective, although the long-term success may be compromised by continuing changes in affected vessels."}
{"id": "PMID:233110", "title": "[Eccrine poroma: its histogenesis and review of the literature].", "content": "It has been done an analysis of a case of eccrine porome, based on the morphology, considering the actual tecnical publications on the matter. The morphogenesis of the formation of this nevoid tumor is established by the continuity between the main body of the tumor and the underneath eccrine sweat glands. These glands present signs of hyperplasia, which in the highest levels present destructuration of the excretory duct and morphological modifications of the cells which are conditioned by the functional adaptation at different levels. In this way there is proliferation of structures, similar to the different parts of syringuium and acrosyringuium producing this hamartomatous neoformation.", "contents": "[Eccrine poroma: its histogenesis and review of the literature]. It has been done an analysis of a case of eccrine porome, based on the morphology, considering the actual tecnical publications on the matter. The morphogenesis of the formation of this nevoid tumor is established by the continuity between the main body of the tumor and the underneath eccrine sweat glands. These glands present signs of hyperplasia, which in the highest levels present destructuration of the excretory duct and morphological modifications of the cells which are conditioned by the functional adaptation at different levels. In this way there is proliferation of structures, similar to the different parts of syringuium and acrosyringuium producing this hamartomatous neoformation."}
{"id": "PMID:233111", "title": "Changes in psychological well-being during postmenopause as a result of estrogen therapy.", "content": "A study of the effects of a conjugated estrogen (Femipren) upon various climacteric symptoms, depression and anxiety scores and psycho-social factors in 120 women around the menopause, was carried out in a Menopause Clinic. In order to participate in this study, the women had to meet very strict criteria. A climacteric symptom list, the MMPI and a psycho-social questionnaire were used for assessment, and were employed before, during and at the end of 1 yr of hormone replacement therapy. Typical vasomotor and psychic symptoms changed significantly as did such factors as self-image, optimism, perception of the future and satisfaction with personal appearance, in those patients who received hormonal replacement therapy for 1 yr. As the psychological factors changed only in those patients who received long-term estrogen therapy, a tentative hypothesis of direct psychotropic effect of estrogen was formulated.", "contents": "Changes in psychological well-being during postmenopause as a result of estrogen therapy. A study of the effects of a conjugated estrogen (Femipren) upon various climacteric symptoms, depression and anxiety scores and psycho-social factors in 120 women around the menopause, was carried out in a Menopause Clinic. In order to participate in this study, the women had to meet very strict criteria. A climacteric symptom list, the MMPI and a psycho-social questionnaire were used for assessment, and were employed before, during and at the end of 1 yr of hormone replacement therapy. Typical vasomotor and psychic symptoms changed significantly as did such factors as self-image, optimism, perception of the future and satisfaction with personal appearance, in those patients who received hormonal replacement therapy for 1 yr. As the psychological factors changed only in those patients who received long-term estrogen therapy, a tentative hypothesis of direct psychotropic effect of estrogen was formulated."}
{"id": "PMID:233112", "title": "Adenosine triphosphatase of mycobacteria.", "content": "A Mg+2-(Ca+2)-activated adenosine triphosphatase activity has been demonstrated in saprophytic, human pathogenic and non-pathogenic, and atypical, species of mycobacteria. (Na+ + K+)-activated adenosine triphosphatase was absent in the species investigated. The effect of age of culture on enzyme activity was revealed in an increase up to mid logarithmic phase of growth, and a decline thereafter. Differences in oxygen tensin during growth did not alter enzyme activity. Isonicotinic acid hydrazide and streptomycin inhibited the enzyme activity.", "contents": "Adenosine triphosphatase of mycobacteria. A Mg+2-(Ca+2)-activated adenosine triphosphatase activity has been demonstrated in saprophytic, human pathogenic and non-pathogenic, and atypical, species of mycobacteria. (Na+ + K+)-activated adenosine triphosphatase was absent in the species investigated. The effect of age of culture on enzyme activity was revealed in an increase up to mid logarithmic phase of growth, and a decline thereafter. Differences in oxygen tensin during growth did not alter enzyme activity. Isonicotinic acid hydrazide and streptomycin inhibited the enzyme activity."}
{"id": "PMID:233122", "title": "Expression of the chromosomal mouse Beta maj-globin gene cloned in SV40.", "content": "The complete chromosomal mouse Beta maj-globin gene, including its intervening and flanking sequences, has been cloned in the monkey virus SV40. the mouse gene is transcribed, processed and translated in infected monkey kidney cells to yield mouse Beta maj-globin.", "contents": "Expression of the chromosomal mouse Beta maj-globin gene cloned in SV40. The complete chromosomal mouse Beta maj-globin gene, including its intervening and flanking sequences, has been cloned in the monkey virus SV40. the mouse gene is transcribed, processed and translated in infected monkey kidney cells to yield mouse Beta maj-globin."}
{"id": "PMID:233124", "title": "Identified neurones isolated from leech CNS make selective connections in culture.", "content": "Neurones cultured in vitro offer distinct advantages for studying how processes grow towards their targets and form synaptic connections. In contrast to the complex events occurring during the development of the nervous system, synapse formation in culture can be analysed in a few neurones at a time and under controlled conditions. We have now dissected out and cultured single identified neurones from the central nervous system (CNS) of the adult leech. Various types of sensory cells, motor cells, and interneurones can be identified in leech ganglia--each with a stereotyped set of properties, including: (1) the electrical characteristics of its membrane, (2) the arborisation of its branches and the morphology of its terminals and (3) the pattern of connections it makes with other identified neurones, skin or muscle. Thus, cultured cells can be compared in detail with their counterparts in situ. We have found that isolated cells survive for several weeks, maintain their membrane properties, sprout and form selective connections.", "contents": "Identified neurones isolated from leech CNS make selective connections in culture. Neurones cultured in vitro offer distinct advantages for studying how processes grow towards their targets and form synaptic connections. In contrast to the complex events occurring during the development of the nervous system, synapse formation in culture can be analysed in a few neurones at a time and under controlled conditions. We have now dissected out and cultured single identified neurones from the central nervous system (CNS) of the adult leech. Various types of sensory cells, motor cells, and interneurones can be identified in leech ganglia--each with a stereotyped set of properties, including: (1) the electrical characteristics of its membrane, (2) the arborisation of its branches and the morphology of its terminals and (3) the pattern of connections it makes with other identified neurones, skin or muscle. Thus, cultured cells can be compared in detail with their counterparts in situ. We have found that isolated cells survive for several weeks, maintain their membrane properties, sprout and form selective connections."}
{"id": "PMID:233125", "title": "A physiological correlate of disuse-induced sprouting at the neuromuscular junction.", "content": "Recent investigations have established that many of the normal properties of muscle fibres are maintained, at least in part, by muscle activity. Thus, a fall in resting membrane potential, an increase in input resistance, and spread of acetylcholine receptors to extrajunctional sites can all be induced by abolishing muscle activity and prevented by direct stimulation of denervated muscle fibres. Muscle activity also exerts a trophic influence on the innervating motoneurones; furthermore it may be a factor in the regulation of sprouting. Brown and Ironton found fine, \"ultra-terminal sprouts\" emanating from the endplates of muscles rendered inactive by chronic conduction block of the muscle nerve. Pestronk and Drachman saw increased branching of the motor nerve terminal and a consequent increase in endplate size in similar conditions. If these sprouts at the endplates of inactive muscles were functional, one might expect more transmitter to be released in response to nerve stimulation. We report here that both quantum content and spontaneous miniature endplate potential (m.e.p.p) frequency are increased at the terminals of inactive (disused) muscles.", "contents": "A physiological correlate of disuse-induced sprouting at the neuromuscular junction. Recent investigations have established that many of the normal properties of muscle fibres are maintained, at least in part, by muscle activity. Thus, a fall in resting membrane potential, an increase in input resistance, and spread of acetylcholine receptors to extrajunctional sites can all be induced by abolishing muscle activity and prevented by direct stimulation of denervated muscle fibres. Muscle activity also exerts a trophic influence on the innervating motoneurones; furthermore it may be a factor in the regulation of sprouting. Brown and Ironton found fine, \"ultra-terminal sprouts\" emanating from the endplates of muscles rendered inactive by chronic conduction block of the muscle nerve. Pestronk and Drachman saw increased branching of the motor nerve terminal and a consequent increase in endplate size in similar conditions. If these sprouts at the endplates of inactive muscles were functional, one might expect more transmitter to be released in response to nerve stimulation. We report here that both quantum content and spontaneous miniature endplate potential (m.e.p.p) frequency are increased at the terminals of inactive (disused) muscles."}
{"id": "PMID:233127", "title": "Epidermal growth factor receptors increase during the differentiation of embryonal carcinoma cells.", "content": "Mouse teratocarcinoma stem cells (embryonal carcinoma, or EC cells) bind very small amounts of mouse epidermal growth factor (EGF) and the latter hormone seems to have no stimulatory effect on the growth of two cloned lines of EC cells. However, when EC cells are induced to differentiate into large flat endodern-like cells (END cells), EGF receptors increase in number reaching a plateau in 6 to 8 days. At 8 to 10 days after induction, END cells multiply very slowly, but when EGF is added (3 x 10(-10) M) to the medium, cell division is stimulated and a further change in morphology occurs. This letter describes the binding characteristics and numbers of the EGF receptors on EC and END cells and shows that exogenous retinoic acid increases the numbers of EGF receptors on END cells. We were unable to find endogenous competing factors produced by EC cells. Such factors could account for the lack of detectable binding of EGF on these cells. As EC cells differentiate to END cells, so the ability of the cells to form tumours is reduced. Since this change is accompanied by an increase in the number of EGF receptors there may be a relationship between these two events.", "contents": "Epidermal growth factor receptors increase during the differentiation of embryonal carcinoma cells. Mouse teratocarcinoma stem cells (embryonal carcinoma, or EC cells) bind very small amounts of mouse epidermal growth factor (EGF) and the latter hormone seems to have no stimulatory effect on the growth of two cloned lines of EC cells. However, when EC cells are induced to differentiate into large flat endodern-like cells (END cells), EGF receptors increase in number reaching a plateau in 6 to 8 days. At 8 to 10 days after induction, END cells multiply very slowly, but when EGF is added (3 x 10(-10) M) to the medium, cell division is stimulated and a further change in morphology occurs. This letter describes the binding characteristics and numbers of the EGF receptors on EC and END cells and shows that exogenous retinoic acid increases the numbers of EGF receptors on END cells. We were unable to find endogenous competing factors produced by EC cells. Such factors could account for the lack of detectable binding of EGF on these cells. As EC cells differentiate to END cells, so the ability of the cells to form tumours is reduced. Since this change is accompanied by an increase in the number of EGF receptors there may be a relationship between these two events."}
{"id": "PMID:233129", "title": "Clindamycin and lincomycin alter miniature endplate current decay.", "content": "Antibiotic-induced muscle paralysis has frequently been found in both experimental animals and man with three distinct classes of antibiotic: (1) streptomycin and related aminoglycoside compounds, (2) polymyxins and (3) tetracyclines. Recently lincomycin and its chemical congener, clindamycin, have been reported to produce muscle paralysis which has different characteristics from those seen with other classes of antibiotic. Although closely related in chemical structure, lincomycin and clindamycin also seem to produce muscle paralysis by different mechanisms. Clindamycin is considered to exert a direct depressant action on muscle contractility whereas the action of lincomycin is considered to be primarily a depression of neuromuscular transmission. We report here that each of these antibiotics had a significant but different influence on endplate channel behaviour. Clindamycin increased the rate of miniature endplate current (m.e.p.c.) decay and reduced its voltage sensitivity without altering its exponential nature. Lincomycin split m.e.p.c. decay into an initial rapid phase followed by a prolonged phase.", "contents": "Clindamycin and lincomycin alter miniature endplate current decay. Antibiotic-induced muscle paralysis has frequently been found in both experimental animals and man with three distinct classes of antibiotic: (1) streptomycin and related aminoglycoside compounds, (2) polymyxins and (3) tetracyclines. Recently lincomycin and its chemical congener, clindamycin, have been reported to produce muscle paralysis which has different characteristics from those seen with other classes of antibiotic. Although closely related in chemical structure, lincomycin and clindamycin also seem to produce muscle paralysis by different mechanisms. Clindamycin is considered to exert a direct depressant action on muscle contractility whereas the action of lincomycin is considered to be primarily a depression of neuromuscular transmission. We report here that each of these antibiotics had a significant but different influence on endplate channel behaviour. Clindamycin increased the rate of miniature endplate current (m.e.p.c.) decay and reduced its voltage sensitivity without altering its exponential nature. Lincomycin split m.e.p.c. decay into an initial rapid phase followed by a prolonged phase."}
{"id": "PMID:233130", "title": "Role of intracellular Ca2+ sequestration in beta-adrenergic relaxation of a smooth muscle.", "content": "Various mechanisms have been proposed for beta-adrenergically mediated relaxation of smooth muscle. All theories suggest the involvement of cyclic AMP as a second messenger: beta-agonists stimulate adenylate cyclase which converts ATP to cyclic AMP and protein kinase, activated by cyclic AMP, is then thought to catalyse a protein phosphorylation that leads to a reduction in free Ca2+, thus effecting relaxation. How this last step is accomplished is much debated, but the following possibilities are currently considered as the mechanisms responsible for cyclic AMP-induced reduction of cytoplasmic Ca2+: activation of a Ca2+-ATPase in the plasma and/or sarcoplasmic reticulum membranes which lowers cytoplasmic [Ca2+] in a direct manner or stimulation of (Na+-K+)ATPase in the cell membrane which may indirectly effect Ca2+ extrusion. Among the hypotheses suggested, those of Ca2+ sequestration by the sarcoplasmic reticulum and of Ca2+ extrusion across the cell membrane are consistent with each other if it is assumed that both processes are effected by a cyclic AMP-sensitive Ca2+-ATPase. However, quite a different mechanism is implied by involving the Na+-K+ pump and Na+-Ca2+ exchange carrier. In this report, we present evidence that suggests intracellular Ca2+ sequestration is the mechanism involved.", "contents": "Role of intracellular Ca2+ sequestration in beta-adrenergic relaxation of a smooth muscle. Various mechanisms have been proposed for beta-adrenergically mediated relaxation of smooth muscle. All theories suggest the involvement of cyclic AMP as a second messenger: beta-agonists stimulate adenylate cyclase which converts ATP to cyclic AMP and protein kinase, activated by cyclic AMP, is then thought to catalyse a protein phosphorylation that leads to a reduction in free Ca2+, thus effecting relaxation. How this last step is accomplished is much debated, but the following possibilities are currently considered as the mechanisms responsible for cyclic AMP-induced reduction of cytoplasmic Ca2+: activation of a Ca2+-ATPase in the plasma and/or sarcoplasmic reticulum membranes which lowers cytoplasmic [Ca2+] in a direct manner or stimulation of (Na+-K+)ATPase in the cell membrane which may indirectly effect Ca2+ extrusion. Among the hypotheses suggested, those of Ca2+ sequestration by the sarcoplasmic reticulum and of Ca2+ extrusion across the cell membrane are consistent with each other if it is assumed that both processes are effected by a cyclic AMP-sensitive Ca2+-ATPase. However, quite a different mechanism is implied by involving the Na+-K+ pump and Na+-Ca2+ exchange carrier. In this report, we present evidence that suggests intracellular Ca2+ sequestration is the mechanism involved."}
{"id": "PMID:233131", "title": "Extracellular but not intracellular application of peptide hormones activates pancreatic acinar cells.", "content": "Peptide hormones, like neurotransmitters, are traditionally thought to activate cells by interacting with receptor sites accessible only from the extracellular space. However, there is no available evidence that establishes whether intracellular injections of peptide secretagogues can or cannot initiate cell activation. In view of recent demonstration that peptide hormones can penetrate the intracellular space in some tissues and the reports that intracellular injections of the neurotransmitter, dopamine, into acinar cells of cockroach salivary gland cause stimulation it seems of fundamental importance to test directly whether introduction of peptide secretagogues inside acinar cells of mammalian exocrine tissue can induce cell activation without first interacting with the outer surface of the external cell membrane. The data presented here show that injections of the secretagogue peptides caerulein and bombesinnonapeptide (bombesin-NP) into pancreatic acinar cells fail to evoke the characteristic potential and conductance changes that are observed following extracellular applications of these peptides.", "contents": "Extracellular but not intracellular application of peptide hormones activates pancreatic acinar cells. Peptide hormones, like neurotransmitters, are traditionally thought to activate cells by interacting with receptor sites accessible only from the extracellular space. However, there is no available evidence that establishes whether intracellular injections of peptide secretagogues can or cannot initiate cell activation. In view of recent demonstration that peptide hormones can penetrate the intracellular space in some tissues and the reports that intracellular injections of the neurotransmitter, dopamine, into acinar cells of cockroach salivary gland cause stimulation it seems of fundamental importance to test directly whether introduction of peptide secretagogues inside acinar cells of mammalian exocrine tissue can induce cell activation without first interacting with the outer surface of the external cell membrane. The data presented here show that injections of the secretagogue peptides caerulein and bombesinnonapeptide (bombesin-NP) into pancreatic acinar cells fail to evoke the characteristic potential and conductance changes that are observed following extracellular applications of these peptides."}
{"id": "PMID:233132", "title": "Correlation between benzodiazepine receptor occupation and anticonvulsant effects of diazepam.", "content": "The benzodiazepines are potent anticonvulsants for a wide variety of experimental and clinical seizure disorders. The demonstration of saturable, high-affinity and stereospecific binding sites for the benzodiazepines in the mammalian central nervous system suggests the presence of pharmacological receptors mediating the anticonvulsant properties of these compounds. The good correlation between the anticonvulsant potencies of a series of benzodiazepines and their ability to inhibit 3H-diazepam binding in vitro further supports this hypothesis, but evidence for a direct interaction between benzodiazepines and their receptors, and a subsequent inhibition of seizure activity (or elevation of seizure threshold) is lacking. Recent reports from our laboratory and others have demonstrated the feasibility of labelling benzodiazepine receptors in vivo following parental administration of tritiated benzodiazepine. This technique permits one to study the relationship between the anticonvulsant activity of the benzodiazepines in vivo and the number of 'drug-occupied' receptors in vitro. We now report that there is an excellent correlation between benzodiazepine receptor occupancy by diazepam and protection against pentylenetetrazol-induced seizures. Furthermore, these results demonstrate that only a small fraction of benzodiazepine receptors need be occupied to produce a complete anticonvulsant effect.", "contents": "Correlation between benzodiazepine receptor occupation and anticonvulsant effects of diazepam. The benzodiazepines are potent anticonvulsants for a wide variety of experimental and clinical seizure disorders. The demonstration of saturable, high-affinity and stereospecific binding sites for the benzodiazepines in the mammalian central nervous system suggests the presence of pharmacological receptors mediating the anticonvulsant properties of these compounds. The good correlation between the anticonvulsant potencies of a series of benzodiazepines and their ability to inhibit 3H-diazepam binding in vitro further supports this hypothesis, but evidence for a direct interaction between benzodiazepines and their receptors, and a subsequent inhibition of seizure activity (or elevation of seizure threshold) is lacking. Recent reports from our laboratory and others have demonstrated the feasibility of labelling benzodiazepine receptors in vivo following parental administration of tritiated benzodiazepine. This technique permits one to study the relationship between the anticonvulsant activity of the benzodiazepines in vivo and the number of 'drug-occupied' receptors in vitro. We now report that there is an excellent correlation between benzodiazepine receptor occupancy by diazepam and protection against pentylenetetrazol-induced seizures. Furthermore, these results demonstrate that only a small fraction of benzodiazepine receptors need be occupied to produce a complete anticonvulsant effect."}
{"id": "PMID:233133", "title": "Glycyrrhizic acid inhibits virus growth and inactivates virus particles.", "content": "Screening investigations in antiviral action of plant extracts have revealed that a component of Glycyrrhiza glabra roots, found to be glycyrrhizie acid, is active against viruses. We report here that this drug inhibits growth and cytopathology of several unrelated DNA and RNA viruses, while not affecting cell activity and ability to replicate. In addition, glycyrrhizic acid inactivates herpes simplex virus particles irreversibly.", "contents": "Glycyrrhizic acid inhibits virus growth and inactivates virus particles. Screening investigations in antiviral action of plant extracts have revealed that a component of Glycyrrhiza glabra roots, found to be glycyrrhizie acid, is active against viruses. We report here that this drug inhibits growth and cytopathology of several unrelated DNA and RNA viruses, while not affecting cell activity and ability to replicate. In addition, glycyrrhizic acid inactivates herpes simplex virus particles irreversibly."}
{"id": "PMID:233136", "title": "Effect of novobiocin on initiation of DNA replication in Bacillus subtilis.", "content": "The initiation of DNA replication of small replicons in vitro involves conformational changes in the whole DNA molecule or in the region near to the replication origin. One striking finding has been the role of DNA gyrase (that is, the necessity for supercoiled structure) in the initial stage of ColE1 replication in vitro. However, little is known about the effect of gyrase on the initiation of replication of bacterial chromosomes in vivo. We have constructed a map of cleavage sites of restriction enzymes at the region of the origin of replication of the Bacillus subtilis chromosome (accompanying paper). This has now enabled us to examine the effect of novobiocin, a selective inhibitor of DNA gyrase, on the replication of the specific chromosomal segments near the origin and to seek a possible role for the gyrase in the initiation of chromosomal replication. We have found that only a limited segment of the chromosome at the origin region was replicated in the presence of novobiocin. This effect allowed us to locate the site of the origin of replication to within a DNA fragment of molecular weight 3.4 x 10(6).", "contents": "Effect of novobiocin on initiation of DNA replication in Bacillus subtilis. The initiation of DNA replication of small replicons in vitro involves conformational changes in the whole DNA molecule or in the region near to the replication origin. One striking finding has been the role of DNA gyrase (that is, the necessity for supercoiled structure) in the initial stage of ColE1 replication in vitro. However, little is known about the effect of gyrase on the initiation of replication of bacterial chromosomes in vivo. We have constructed a map of cleavage sites of restriction enzymes at the region of the origin of replication of the Bacillus subtilis chromosome (accompanying paper). This has now enabled us to examine the effect of novobiocin, a selective inhibitor of DNA gyrase, on the replication of the specific chromosomal segments near the origin and to seek a possible role for the gyrase in the initiation of chromosomal replication. We have found that only a limited segment of the chromosome at the origin region was replicated in the presence of novobiocin. This effect allowed us to locate the site of the origin of replication to within a DNA fragment of molecular weight 3.4 x 10(6)."}
{"id": "PMID:233137", "title": "Controlled synthesis of HBsAg in a differentiated human liver carcinoma-derived cell line.", "content": "A significant aspect of primary hepatic carcinoma in man is the high positive correlation of hepatocellular carcinoma with infection with hepatitis B virus (HBV)1. Analysis of the relationship between HBV infection and oncogenesis is difficult because natural infection with HBV is limited to man and experimental infection has been achieved only in chimpanzees and gibbons. Furthermore, because HBV has not been successfully propagated in cell culture, basic study of virus-cell interaction of the aetiological agent of one of the most widespread infections of man has been impossible. Recently, however, a cell line (PLC/PRF/5) derived from a human hepatoma biopsy was described which produces the HRV surface antigen (HBsAg) and so provides a tool for the experimental investigation of HBV in viro. We now report the derivation and characterisation of two additional cell lines primary liver carcinomas. In contrast to the PLC/PRF/5 cell line, these cell lines retain the capacity to synthesise many human plasma proteins, including both albumin and alpha-fetoprotein (AFP). One of these lines also produces BHsAg. We also present evidence that HBsAg synthesis and secretion in this cell line are correlated with the growth state of the culture. This finding is in contrast to the continuous HBsAg production found in the PLC/PRF/5 cell line.", "contents": "Controlled synthesis of HBsAg in a differentiated human liver carcinoma-derived cell line. A significant aspect of primary hepatic carcinoma in man is the high positive correlation of hepatocellular carcinoma with infection with hepatitis B virus (HBV)1. Analysis of the relationship between HBV infection and oncogenesis is difficult because natural infection with HBV is limited to man and experimental infection has been achieved only in chimpanzees and gibbons. Furthermore, because HBV has not been successfully propagated in cell culture, basic study of virus-cell interaction of the aetiological agent of one of the most widespread infections of man has been impossible. Recently, however, a cell line (PLC/PRF/5) derived from a human hepatoma biopsy was described which produces the HRV surface antigen (HBsAg) and so provides a tool for the experimental investigation of HBV in viro. We now report the derivation and characterisation of two additional cell lines primary liver carcinomas. In contrast to the PLC/PRF/5 cell line, these cell lines retain the capacity to synthesise many human plasma proteins, including both albumin and alpha-fetoprotein (AFP). One of these lines also produces BHsAg. We also present evidence that HBsAg synthesis and secretion in this cell line are correlated with the growth state of the culture. This finding is in contrast to the continuous HBsAg production found in the PLC/PRF/5 cell line."}
{"id": "PMID:233145", "title": "The isolation and cultivation of calf rotavirus in the Republic of South Africa.", "content": "Calf rotavirus was cultivated and propagated in tissue culture from faeces of 3-week-old calves suffering from severe diarrhoea. Criteria for viral involvement were: production of cytopathic effect in primary foetal calf kidney cells, specific fluorescence, and identification of the agent by means of electron microscopy. In a limited serological survey the majority of the cows on an infested farm were found to possess neutralizing antibodies to the local rotavirus strain.", "contents": "The isolation and cultivation of calf rotavirus in the Republic of South Africa. Calf rotavirus was cultivated and propagated in tissue culture from faeces of 3-week-old calves suffering from severe diarrhoea. Criteria for viral involvement were: production of cytopathic effect in primary foetal calf kidney cells, specific fluorescence, and identification of the agent by means of electron microscopy. In a limited serological survey the majority of the cows on an infested farm were found to possess neutralizing antibodies to the local rotavirus strain."}
{"id": "PMID:233146", "title": "Genetic and physiological characterization of temperature-sensitive mutants of bluetongue virus.", "content": "Complementation studies were carried out, using temperature-sensitive (t-s) mutants of blue-tongue virus (BTV). The results proved to be inconclusive as only low indices of complementation were obtained. No discrepancy was found between the previous classification of these mutants in 6 recombination classes and the complementation data recored. In general, the t-s mutants require a latent growth period of 16-20 h at 28 degrees C and maximum titres can be demonstrated 40-48 h post-infection. One mutant, (F211), however, consistently had a growth lag phase of 32 h. Mutants of the 6 recombination groups were further classified into 2 groups by temperature-shift studies. One calss of mutants expressed their t-s lesion prior to 24 h and the other class only after 24 h post-infection. Mutant F73 was found to be defective in its ability to synthesize ssRNA at a late stage in the replication cycle at the non-permissive temperature.", "contents": "Genetic and physiological characterization of temperature-sensitive mutants of bluetongue virus. Complementation studies were carried out, using temperature-sensitive (t-s) mutants of blue-tongue virus (BTV). The results proved to be inconclusive as only low indices of complementation were obtained. No discrepancy was found between the previous classification of these mutants in 6 recombination classes and the complementation data recored. In general, the t-s mutants require a latent growth period of 16-20 h at 28 degrees C and maximum titres can be demonstrated 40-48 h post-infection. One mutant, (F211), however, consistently had a growth lag phase of 32 h. Mutants of the 6 recombination groups were further classified into 2 groups by temperature-shift studies. One calss of mutants expressed their t-s lesion prior to 24 h and the other class only after 24 h post-infection. Mutant F73 was found to be defective in its ability to synthesize ssRNA at a late stage in the replication cycle at the non-permissive temperature."}
{"id": "PMID:233147", "title": "The nucleic acid and proteins of epizootic haemorrhagic disease virus.", "content": "Purified epizootic haemorrhagic disease virus (EHDV) was shown to contain 10 double-stranded RNA segments and a double-layered protein capsid with 4 major and 4 minor polypeptides. The virus differed from bluetongue virus (BTV), the orbivirus prototype, in that EHDV had an additional minor polypeptide component. This component, together with the major polypeptides P2 and P5, formed the outer capsid layer of the virus. The extra polypeptide apparently stabilizes this layer since, unlike BTV, EHDV was quite stable on CsCl gradients at both pH 7,0 and 8,0. EHD virions were found to have a density of 1,36 g/microliter, while particles without the outer capsid layer were isolated and had a density of 1,40 g/microliter. Two non-capsid polypeptides, P5A and P6A, were identified in addition to the 8 capsid polypeptides. Polypeptide P5A was synthesized in excess of all the others. There was little homology between the nucleic acids of EHDV and BTV with only 5-10% cross-hybridization. No hybrid double-stranded RNA segments were identified. We found by cross-immune precipitation that the major core polypeptides of the 2 viruses (P7 and P3) have common antigenic determinants.", "contents": "The nucleic acid and proteins of epizootic haemorrhagic disease virus. Purified epizootic haemorrhagic disease virus (EHDV) was shown to contain 10 double-stranded RNA segments and a double-layered protein capsid with 4 major and 4 minor polypeptides. The virus differed from bluetongue virus (BTV), the orbivirus prototype, in that EHDV had an additional minor polypeptide component. This component, together with the major polypeptides P2 and P5, formed the outer capsid layer of the virus. The extra polypeptide apparently stabilizes this layer since, unlike BTV, EHDV was quite stable on CsCl gradients at both pH 7,0 and 8,0. EHD virions were found to have a density of 1,36 g/microliter, while particles without the outer capsid layer were isolated and had a density of 1,40 g/microliter. Two non-capsid polypeptides, P5A and P6A, were identified in addition to the 8 capsid polypeptides. Polypeptide P5A was synthesized in excess of all the others. There was little homology between the nucleic acids of EHDV and BTV with only 5-10% cross-hybridization. No hybrid double-stranded RNA segments were identified. We found by cross-immune precipitation that the major core polypeptides of the 2 viruses (P7 and P3) have common antigenic determinants."}
{"id": "PMID:233148", "title": "Isolation and characterization of antibodies to Clostridium perfringens epsilon toxin from hyperimmune horse serum.", "content": "Antibodies against epsilon toxin were isolated from hyperimmune horse serum by affinity chromatography. Purified epsilon prototoxin covalently bound to Affigel 202 was used as immunosorbent, and antibodies were eluted with 6.0 M guanidine chloride. In a single run 80 mg of antibody could be recovered from a 20 microliter column of immunosorbent. The antibody was shown to belong to the IgG(T) class of immunoglobulins.", "contents": "Isolation and characterization of antibodies to Clostridium perfringens epsilon toxin from hyperimmune horse serum. Antibodies against epsilon toxin were isolated from hyperimmune horse serum by affinity chromatography. Purified epsilon prototoxin covalently bound to Affigel 202 was used as immunosorbent, and antibodies were eluted with 6.0 M guanidine chloride. In a single run 80 mg of antibody could be recovered from a 20 microliter column of immunosorbent. The antibody was shown to belong to the IgG(T) class of immunoglobulins."}
{"id": "PMID:233149", "title": "Further characterization of the t-s mutant F207 of bluetongue virus.", "content": "Temperature-shift experiments verified that the t-s lesion of BTV mutant F207 is expressed late in the replication-cycle, that is, at a stage when all virus components have already been synthesized. All viral polypeptides were indeed found in the soluble but not in the particulate fraction of cytoplasmic extracts from infected cultures grown at the non-permissive temperature. This suggests that the t-s lesion could be a defect in one or both of the polypeptides P2 and P5, which are respectively reduced in amount and absent from the latter fraction. Alternatively, the lesion could be an inability of the core particle to bind these 2 outer capsid polypeptides.", "contents": "Further characterization of the t-s mutant F207 of bluetongue virus. Temperature-shift experiments verified that the t-s lesion of BTV mutant F207 is expressed late in the replication-cycle, that is, at a stage when all virus components have already been synthesized. All viral polypeptides were indeed found in the soluble but not in the particulate fraction of cytoplasmic extracts from infected cultures grown at the non-permissive temperature. This suggests that the t-s lesion could be a defect in one or both of the polypeptides P2 and P5, which are respectively reduced in amount and absent from the latter fraction. Alternatively, the lesion could be an inability of the core particle to bind these 2 outer capsid polypeptides."}
{"id": "PMID:233150", "title": "Development and suppression of a population of late-adhering macrophages in mouse malaria.", "content": "Changes in phagocytic and adherent cell numbers were compared during the course of infections of mice with Plasmodium yoelii (Py) and P. berghei (Pb) and in vaccinated mice challenged with homologous parasites. Nucleated cells in the spleen increased in number in Py-infected mice and were maximal at the time of recovery. The number of phagocytic cells increased in parallel, as did the number of blood leucocytes. Rates of increase were accelerated in vaccinated mice. Changes in Pb-infected mice resembled controls and blood leucocytes showed no consistent increase. In infected mice, the number of spleen and bone marrow cells which adhered to plastic rose above normal. At some stages of infection, cells which did not adhere in 24 h did so in 72 h. Such late-adhering cells, which resembled macrophages in morphology, were most numerous at the time of recovery. They appeared to be derived from monocyte precursors which matured in culture. Sometimes cells adherent at 24 h suppressed the development of the late-adhering population. Silica invactivated these suppressive macrophages but did not affect the precursors which developed into late-adhering cells. It is concluded that malarial infection stimulates the production of precursors of the macrophage-monocyte series and that their development is regulated by the presence of mature macrophages.", "contents": "Development and suppression of a population of late-adhering macrophages in mouse malaria. Changes in phagocytic and adherent cell numbers were compared during the course of infections of mice with Plasmodium yoelii (Py) and P. berghei (Pb) and in vaccinated mice challenged with homologous parasites. Nucleated cells in the spleen increased in number in Py-infected mice and were maximal at the time of recovery. The number of phagocytic cells increased in parallel, as did the number of blood leucocytes. Rates of increase were accelerated in vaccinated mice. Changes in Pb-infected mice resembled controls and blood leucocytes showed no consistent increase. In infected mice, the number of spleen and bone marrow cells which adhered to plastic rose above normal. At some stages of infection, cells which did not adhere in 24 h did so in 72 h. Such late-adhering cells, which resembled macrophages in morphology, were most numerous at the time of recovery. They appeared to be derived from monocyte precursors which matured in culture. Sometimes cells adherent at 24 h suppressed the development of the late-adhering population. Silica invactivated these suppressive macrophages but did not affect the precursors which developed into late-adhering cells. It is concluded that malarial infection stimulates the production of precursors of the macrophage-monocyte series and that their development is regulated by the presence of mature macrophages."}
{"id": "PMID:233154", "title": "Muscarinic supersensitivity: a possible model for the sleep disturbance of primary depression?", "content": "The sleep changes induced in normal volunteers following the administration of scopolamine on 3 consecutive mornings resemble many of the abnormalities observed in the sleep of patients with primary depression: increased sleep latency and reduced rapid eye movement (REM) latency, total sleep time, and sleep efficiency. Furthermore, in a multivariate discriminant analysis--previously shown to distinguish the sleep records of depresed patients from those of normal controls and insomniac patients--the records from baseline nights were selected as normal and those after scopolamine as predominately depressed. Those observations suggest to us that muscarinic supersensitivity in normals may function as a pharmacological model for the sleep disturbances of depression.", "contents": "Muscarinic supersensitivity: a possible model for the sleep disturbance of primary depression? The sleep changes induced in normal volunteers following the administration of scopolamine on 3 consecutive mornings resemble many of the abnormalities observed in the sleep of patients with primary depression: increased sleep latency and reduced rapid eye movement (REM) latency, total sleep time, and sleep efficiency. Furthermore, in a multivariate discriminant analysis--previously shown to distinguish the sleep records of depresed patients from those of normal controls and insomniac patients--the records from baseline nights were selected as normal and those after scopolamine as predominately depressed. Those observations suggest to us that muscarinic supersensitivity in normals may function as a pharmacological model for the sleep disturbances of depression."}
{"id": "PMID:233155", "title": "Scopolamine-induced muscarinic supersensitivity in normal man: changes in sleep.", "content": "Scopolamine (6 microgram/kg) was administered on 3 consecutive mornings to normal human subjects. Sleep recordings obtained at night (when the central anticholinergic effect of the morning scopolamine was no longer present) indicated a significant reduction in latency to REM-sleep onset on the nights following the second and third injections. This effect is opposite to the direct pharmacological action of nighttime administration of scopolamine (i.e., prolongation of REM latency). In addition, total sleep time and sleep efficiency were reduced, and sleep latency was increased. Furthermore, scopolamine pretreatment on 2 consecutive mornings also potentiated the REM-inducing effect of arecoline, a central muscarinic agonist. These data are consistent with the development of cholinergic supersensitivity following cholinergic blockade.", "contents": "Scopolamine-induced muscarinic supersensitivity in normal man: changes in sleep. Scopolamine (6 microgram/kg) was administered on 3 consecutive mornings to normal human subjects. Sleep recordings obtained at night (when the central anticholinergic effect of the morning scopolamine was no longer present) indicated a significant reduction in latency to REM-sleep onset on the nights following the second and third injections. This effect is opposite to the direct pharmacological action of nighttime administration of scopolamine (i.e., prolongation of REM latency). In addition, total sleep time and sleep efficiency were reduced, and sleep latency was increased. Furthermore, scopolamine pretreatment on 2 consecutive mornings also potentiated the REM-inducing effect of arecoline, a central muscarinic agonist. These data are consistent with the development of cholinergic supersensitivity following cholinergic blockade."}
{"id": "PMID:233156", "title": "EEG sleep and affective psychoses: I. Schizoaffective disorders.", "content": "The sleep electroencephalogram (EEG) was studied in 41 depressed inpatients. EEG sleep records were compared for two diagnostic subgroups; patients with psychotic depression (n = 29) or with schizoaffective disorders (n = 12). As was true in the previous pilot study, no major EEG sleep variables distinguished the patients with psychotic depression from those with schizoaffective disorders. These data are consistent with the theory that all psychotic depressive states may have certain common psychobiologic features such as shortened rapid eye movement (REM) sleep latency.", "contents": "EEG sleep and affective psychoses: I. Schizoaffective disorders. The sleep electroencephalogram (EEG) was studied in 41 depressed inpatients. EEG sleep records were compared for two diagnostic subgroups; patients with psychotic depression (n = 29) or with schizoaffective disorders (n = 12). As was true in the previous pilot study, no major EEG sleep variables distinguished the patients with psychotic depression from those with schizoaffective disorders. These data are consistent with the theory that all psychotic depressive states may have certain common psychobiologic features such as shortened rapid eye movement (REM) sleep latency."}
{"id": "PMID:233157", "title": "Changes in lymphocyte beta-adrenergic receptors in depression and mania.", "content": "The beta-adrenergic receptors were studied in vitro in lymphocytes obtained from patients with major affective disorders and controls. Specific L-[3H]-dihydroalprenolol binding was decreased in both depressed and manic patients compared to controls and euthymic patients. Isoproterenol-stimulated, but not prostaglandin El-stimulated, cyclic adenosine-3',5'-monophosphate production was decreased in manic and depressed patients. These results suggest decreased lymphocyte beta-receptor functioning in depression and mania. This decrease may be an index of changes in brain beta-receptors in mania and depression, or may simply reflect homeostatic regulation of peripheral beta-receptors in response to stress-induced increases in circulating catecholamines.", "contents": "Changes in lymphocyte beta-adrenergic receptors in depression and mania. The beta-adrenergic receptors were studied in vitro in lymphocytes obtained from patients with major affective disorders and controls. Specific L-[3H]-dihydroalprenolol binding was decreased in both depressed and manic patients compared to controls and euthymic patients. Isoproterenol-stimulated, but not prostaglandin El-stimulated, cyclic adenosine-3',5'-monophosphate production was decreased in manic and depressed patients. These results suggest decreased lymphocyte beta-receptor functioning in depression and mania. This decrease may be an index of changes in brain beta-receptors in mania and depression, or may simply reflect homeostatic regulation of peripheral beta-receptors in response to stress-induced increases in circulating catecholamines."}
{"id": "PMID:233158", "title": "MAO activity and EEG sleep in primary depression.", "content": "Platelet monoamine oxidase (MAO) activity and electroencephalographic (EEG) sleep measures were examined in 56 drug-free hospitalized patients with primary depression as defined by the Research Diagnostic Criteria. The group included 35 females and 21 males with a mean age of 42.6 +/- 1.4 years. Platelet MAO and EEG sleep data were compared for the group as a whole and separately for the unipolar, bipolar, male, and female subgroups. No significant relationships could be demonstrated for the entire group or for the unipolar, male, or female subgroups. However, an inverse relationship between MAO activity and REM sleep percent was noted in the bipolar subgroup (p < 0.02). While changes in REM sleep have been relatively firmly established in primary depression, the relationship of MAO to depression and to REM sleep remains unclear.", "contents": "MAO activity and EEG sleep in primary depression. Platelet monoamine oxidase (MAO) activity and electroencephalographic (EEG) sleep measures were examined in 56 drug-free hospitalized patients with primary depression as defined by the Research Diagnostic Criteria. The group included 35 females and 21 males with a mean age of 42.6 +/- 1.4 years. Platelet MAO and EEG sleep data were compared for the group as a whole and separately for the unipolar, bipolar, male, and female subgroups. No significant relationships could be demonstrated for the entire group or for the unipolar, male, or female subgroups. However, an inverse relationship between MAO activity and REM sleep percent was noted in the bipolar subgroup (p < 0.02). While changes in REM sleep have been relatively firmly established in primary depression, the relationship of MAO to depression and to REM sleep remains unclear."}
{"id": "PMID:233159", "title": "Dopamine-mediated behavior produced by the enkephalin analogue FK 33-824.", "content": "Intraperitoneal injection of FK 33-824 produced apomorphine-like stereotyped behavior in rats. Antagonism of this stereotypy by naloxone and neuroleptics suggests that FK 33-824 can activate opiate and dopamine receptors in the brain. Because increased dopaminergic neuronal activity is thought to be involved in schizophrenia and dopamine-mediated stereotypy has been used as an animal model for this illness, these results are consistent with an involvement of endogenous opiate-like peptides in schizophrenia. This involvement provides a possible mechanism for the reported improvement in schizophrenic psychosis produced by naloxone.", "contents": "Dopamine-mediated behavior produced by the enkephalin analogue FK 33-824. Intraperitoneal injection of FK 33-824 produced apomorphine-like stereotyped behavior in rats. Antagonism of this stereotypy by naloxone and neuroleptics suggests that FK 33-824 can activate opiate and dopamine receptors in the brain. Because increased dopaminergic neuronal activity is thought to be involved in schizophrenia and dopamine-mediated stereotypy has been used as an animal model for this illness, these results are consistent with an involvement of endogenous opiate-like peptides in schizophrenia. This involvement provides a possible mechanism for the reported improvement in schizophrenic psychosis produced by naloxone."}
{"id": "PMID:233160", "title": "Low dose fluphenazine decanoate in maintenance treatment of schizophrenia.", "content": "To test the clinical efficacy of low dose fluphenazine decanoate (1.25 mg to 5.0 mg biweekly), we carried out two separate experiments: (1) an open trial in 57 schizophrenic outpatients, lasting 6 months; (2) a double-blind, placebo-controlled discontinuation study in a subgroup of patients who maintained good remission throughout the entire 6-month open trial. The results suggest that lower doses of fluphenazine decanoate than those usually used may be effective in preventing psychotic relapse while keeping total cumulative dosage to a minimum.", "contents": "Low dose fluphenazine decanoate in maintenance treatment of schizophrenia. To test the clinical efficacy of low dose fluphenazine decanoate (1.25 mg to 5.0 mg biweekly), we carried out two separate experiments: (1) an open trial in 57 schizophrenic outpatients, lasting 6 months; (2) a double-blind, placebo-controlled discontinuation study in a subgroup of patients who maintained good remission throughout the entire 6-month open trial. The results suggest that lower doses of fluphenazine decanoate than those usually used may be effective in preventing psychotic relapse while keeping total cumulative dosage to a minimum."}
{"id": "PMID:233166", "title": "Pertussis toxin: the cause of the harmful effects and prolonged immunity of whooping cough. A hypothesis.", "content": "The nature of the pathogenesis and of the prolonged immunity of whooping cough has not been clearly defined. The literature of Bordetella pertussis indicated that only the antigen that induces histamine sensitization, lymphocytosis, and other biological reactions in mice is the cause of the harmful effects and prolonged immunity of whooping cough. This antigen has the general characteristics of bacterial protein exotoxins that cause the harmful effects of infectious diseases such as diphtheria and tetanus. It is proposed that this antigen, which is histamine-sensitizing, lymphocyte-leukocyte-promoting, and islets-activating (HSF-LPF-IAP), be designated pertussis toxin. Agglutinogen, hemagglutinin, and heat-labile (at 56 C) and heat-stable (at 100 C) toxins are no doubt interrelated with the immunologic and/or toxic reactions of whooping cough. It appears that the first defense against the disease is the antibody that prevents adhesion of the bacteria to the cilia of the respiratory epithelium and that the second defense is the antitoxin against pertussis toxin (HSF-LPF-IAP).", "contents": "Pertussis toxin: the cause of the harmful effects and prolonged immunity of whooping cough. A hypothesis. The nature of the pathogenesis and of the prolonged immunity of whooping cough has not been clearly defined. The literature of Bordetella pertussis indicated that only the antigen that induces histamine sensitization, lymphocytosis, and other biological reactions in mice is the cause of the harmful effects and prolonged immunity of whooping cough. This antigen has the general characteristics of bacterial protein exotoxins that cause the harmful effects of infectious diseases such as diphtheria and tetanus. It is proposed that this antigen, which is histamine-sensitizing, lymphocyte-leukocyte-promoting, and islets-activating (HSF-LPF-IAP), be designated pertussis toxin. Agglutinogen, hemagglutinin, and heat-labile (at 56 C) and heat-stable (at 100 C) toxins are no doubt interrelated with the immunologic and/or toxic reactions of whooping cough. It appears that the first defense against the disease is the antibody that prevents adhesion of the bacteria to the cilia of the respiratory epithelium and that the second defense is the antitoxin against pertussis toxin (HSF-LPF-IAP)."}
{"id": "PMID:233167", "title": "Differential diagnosis of infant botulism.", "content": "Clinical investigations of infants hospitalized with botulism demonstrate a remarkable uniformity of complaints and physical findings. Constipation precedes a course of progressive weakness and cranial nerve dysfunction. Examination reveals hypotonia, hyporeflexia, and a variable pattern of involvement of the motor cranial nerves. Initial laboratory investigations should include electrodiagnostic tests, because findings of an incremental response to rapid, repetitive nerve stimulation and of brief, small-amplitude motor units on electromyography are virtually pathognomonic of botulism in the infant. Differential diagnosis includes disorders that may produce generalized depression of the central nervous system, such as septicemia, meningitis, metabolic disturbances, and intoxications. Specific involvement of the neuromuscular system includes acute polyneuropathies, diseases of the anterior horn cell, congenital myopathies or muscular dystrophy, and neonatal myasthenia gravis. Recent studies have expanded the clinical spectrum of infant botulism to include some cases of sudden infant death syndrome and otherwise nonspecific constipation.", "contents": "Differential diagnosis of infant botulism. Clinical investigations of infants hospitalized with botulism demonstrate a remarkable uniformity of complaints and physical findings. Constipation precedes a course of progressive weakness and cranial nerve dysfunction. Examination reveals hypotonia, hyporeflexia, and a variable pattern of involvement of the motor cranial nerves. Initial laboratory investigations should include electrodiagnostic tests, because findings of an incremental response to rapid, repetitive nerve stimulation and of brief, small-amplitude motor units on electromyography are virtually pathognomonic of botulism in the infant. Differential diagnosis includes disorders that may produce generalized depression of the central nervous system, such as septicemia, meningitis, metabolic disturbances, and intoxications. Specific involvement of the neuromuscular system includes acute polyneuropathies, diseases of the anterior horn cell, congenital myopathies or muscular dystrophy, and neonatal myasthenia gravis. Recent studies have expanded the clinical spectrum of infant botulism to include some cases of sudden infant death syndrome and otherwise nonspecific constipation."}
{"id": "PMID:233168", "title": "The action of botulinal toxin.", "content": "Two areas of research on botulinal toxin are reviewed: (1) isolation and characterization of the toxin molecule and (2) the mechanism by which the toxin acts to paralyze transmission by cholingerrgic nerves. The various molecules of botulinal toxin (types A, B, D, E and F) have molecular weights of approximately 150,000. The toxins are composed of two subunits with molecular weights of approximately 100,000 and approximately 50,000, respectively. The subunits are linked by one or more disulfide bonds. The large-molecular-weight substance (approximately 150,000) is fully neurotoxic; neither subunit possesses neurotoxicity. Toxin-induced paralysis of cholingergic nerves involves three steps: (1) an initial binding step that involves an external receptor; (2) a translocation step during which the toxin molecule, or some portion of it, moves through the nerve membrane; and (3) a paralytic step during which the release of acetylcholine is blocked.", "contents": "The action of botulinal toxin. Two areas of research on botulinal toxin are reviewed: (1) isolation and characterization of the toxin molecule and (2) the mechanism by which the toxin acts to paralyze transmission by cholingerrgic nerves. The various molecules of botulinal toxin (types A, B, D, E and F) have molecular weights of approximately 150,000. The toxins are composed of two subunits with molecular weights of approximately 100,000 and approximately 50,000, respectively. The subunits are linked by one or more disulfide bonds. The large-molecular-weight substance (approximately 150,000) is fully neurotoxic; neither subunit possesses neurotoxicity. Toxin-induced paralysis of cholingergic nerves involves three steps: (1) an initial binding step that involves an external receptor; (2) a translocation step during which the toxin molecule, or some portion of it, moves through the nerve membrane; and (3) a paralytic step during which the release of acetylcholine is blocked."}
{"id": "PMID:233169", "title": "Processes of transport and absorption in the developing infant intestine.", "content": "An understanding of changes in the processes of absorption, detoxification, and intoxication in the intestine of infants, especially during the perinatal period, may aid in reaching an understanding of why the syndrome of infant botulism is restricted to the first six months of life. Some of the important metabolic changes associated with both the perinatal and the postnatal period of development are emphasized in these studies. A more complete understanding of the processes by which substances are absorbed into the intestine and then reexposed via the enterohepatic circulation may provide clues about why infant botulism occurs.", "contents": "Processes of transport and absorption in the developing infant intestine. An understanding of changes in the processes of absorption, detoxification, and intoxication in the intestine of infants, especially during the perinatal period, may aid in reaching an understanding of why the syndrome of infant botulism is restricted to the first six months of life. Some of the important metabolic changes associated with both the perinatal and the postnatal period of development are emphasized in these studies. A more complete understanding of the processes by which substances are absorbed into the intestine and then reexposed via the enterohepatic circulation may provide clues about why infant botulism occurs."}
{"id": "PMID:233174", "title": "The prevention of pig-bel in Papua New Guinea.", "content": "In many Highlands hospitals pig-bel is the commonest cause of death in children over 12 months of age. In a double blind controlled trial in Sina Sina we have shown that Clostridium welchii type C beta toxoid (beta toxoid) protects against pig-bel (p < 0.02). Of 2,538 children given beta toxoid, two developed pig-bel in the following two years. Seventeen of 2,532 control children vaccinated with tetanus toxoid developed pig-bel. We suggest that beta toxoid be given to Highlands children at two, four and six months of age. Boosters may be needed. Health services in the Highlands need to be improved so that this vaccine can be effectively delivered.", "contents": "The prevention of pig-bel in Papua New Guinea. In many Highlands hospitals pig-bel is the commonest cause of death in children over 12 months of age. In a double blind controlled trial in Sina Sina we have shown that Clostridium welchii type C beta toxoid (beta toxoid) protects against pig-bel (p < 0.02). Of 2,538 children given beta toxoid, two developed pig-bel in the following two years. Seventeen of 2,532 control children vaccinated with tetanus toxoid developed pig-bel. We suggest that beta toxoid be given to Highlands children at two, four and six months of age. Boosters may be needed. Health services in the Highlands need to be improved so that this vaccine can be effectively delivered."}
{"id": "PMID:233171", "title": "Effects of murine cytomegalovirus infection on the immune response to a tumor allograft.", "content": "The purpose of this study was to compare the effects of murine cytomegalovirus infection introduced after an EL4 ascites tumor allograft with cytomegalovirus infection accompanying or preceding the allograft. Parameters that were measured included documentation to the host's immune system. Depressed immune response of splenocytes from mice infected at any time before assay was documented by decreased responsiveness to phytohemagglutinin, to lipopolysaccharide, and to an alloantigen in mixed lymphocyte culture. In contrast, animals infected after grafting had enhanced lymphocyte-mediated cytolysis (LMC), enhanced serum-mediated cytolysis (SMC), and larger spleens than did animals that were only grafted and animals that were infected before grafting. Neither a depressive nor an enhancing effect of virus administered after grafting was reflected in vivo in reduced or increased graft clearance. Nonspecific effects of virus increased LMC and SMC in vitro, but the primary effect of viral infection after grafting is immune depression.", "contents": "Effects of murine cytomegalovirus infection on the immune response to a tumor allograft. The purpose of this study was to compare the effects of murine cytomegalovirus infection introduced after an EL4 ascites tumor allograft with cytomegalovirus infection accompanying or preceding the allograft. Parameters that were measured included documentation to the host's immune system. Depressed immune response of splenocytes from mice infected at any time before assay was documented by decreased responsiveness to phytohemagglutinin, to lipopolysaccharide, and to an alloantigen in mixed lymphocyte culture. In contrast, animals infected after grafting had enhanced lymphocyte-mediated cytolysis (LMC), enhanced serum-mediated cytolysis (SMC), and larger spleens than did animals that were only grafted and animals that were infected before grafting. Neither a depressive nor an enhancing effect of virus administered after grafting was reflected in vivo in reduced or increased graft clearance. Nonspecific effects of virus increased LMC and SMC in vitro, but the primary effect of viral infection after grafting is immune depression."}
{"id": "PMID:233172", "title": "The possible role of Epstein-Barr virus in rheumatoid arthritis.", "content": "The sera of patients with rheumatoid arthritis form a precipitate with an antigen present in the sonicate of a human B (bone marrow-derived) lymphoid cell line (WiL2). The antibody is distinct from rheumatoid factor. The antigen can be demonstrated by an immunofluorescence technique to be distributed within the nucleus of the WiL2 cell and shows a discrete speckled pattern of nuclear staining. The nuclear antigen is not detectable in organ extracts from many animal species or in human T (thymus-derived) lymphoid cell lines. The current evidence suggests that the nuclear antigen is detectable only in human B lymphoid cells infected with Epstein-Barr virus. It is not clear at present whether the nuclear antigen is a viral protein or a cell protein induced by the Epstein-Barr virus as a result of polyclonal B cell activation.", "contents": "The possible role of Epstein-Barr virus in rheumatoid arthritis. The sera of patients with rheumatoid arthritis form a precipitate with an antigen present in the sonicate of a human B (bone marrow-derived) lymphoid cell line (WiL2). The antibody is distinct from rheumatoid factor. The antigen can be demonstrated by an immunofluorescence technique to be distributed within the nucleus of the WiL2 cell and shows a discrete speckled pattern of nuclear staining. The nuclear antigen is not detectable in organ extracts from many animal species or in human T (thymus-derived) lymphoid cell lines. The current evidence suggests that the nuclear antigen is detectable only in human B lymphoid cells infected with Epstein-Barr virus. It is not clear at present whether the nuclear antigen is a viral protein or a cell protein induced by the Epstein-Barr virus as a result of polyclonal B cell activation."}
{"id": "PMID:233177", "title": "Clostridium welchii type C antitoxin in the treatment of \"pig bel\" (enteritis necroticans): a controlled trial in Papua New Guinea.", "content": "Enteritis necroticans remains a serious problem in the Highlands of Papua New Guinea. Earlier claims that Clostridium Welchii Type C antitoxin is effective in lowering mortality rates were subjected to a prospective controlled trial in 1972-73. Use of the antitoxin was found to be of no benefit in treatment of this disease.", "contents": "Clostridium welchii type C antitoxin in the treatment of \"pig bel\" (enteritis necroticans): a controlled trial in Papua New Guinea. Enteritis necroticans remains a serious problem in the Highlands of Papua New Guinea. Earlier claims that Clostridium Welchii Type C antitoxin is effective in lowering mortality rates were subjected to a prospective controlled trial in 1972-73. Use of the antitoxin was found to be of no benefit in treatment of this disease."}
{"id": "PMID:233181", "title": "Non-linear dynamic phenomena in open reconstituted enzyme systems.", "content": "The dynamic pattern of an open reconstituted in-vitro enzyme system containing phosphofructokinase, pyruvate kinase and adenylate kinase has been investigated. The approach is experimentally based on a stirred flow-through reactor. Stationary concentrations of phosphofructokinase and pyruvate kinase are maintained by entrapment in polyacrylamide gel particles. The results fit to a theoretical model based on the initial kinetic responses of the enzymes involved. An S-shaped steady state input characteristic for fructose 6-phosphate has been experimentally obtained.", "contents": "Non-linear dynamic phenomena in open reconstituted enzyme systems. The dynamic pattern of an open reconstituted in-vitro enzyme system containing phosphofructokinase, pyruvate kinase and adenylate kinase has been investigated. The approach is experimentally based on a stirred flow-through reactor. Stationary concentrations of phosphofructokinase and pyruvate kinase are maintained by entrapment in polyacrylamide gel particles. The results fit to a theoretical model based on the initial kinetic responses of the enzymes involved. An S-shaped steady state input characteristic for fructose 6-phosphate has been experimentally obtained."}
{"id": "PMID:233182", "title": "Proteins of bovine leudemia virus: p. 15 is the major phosphorprotein.", "content": "Sodium dodecylsulfate-polyacrylamide gel electrophoresis of bovine leukemia virus (BLV) grown in fetal lamb kidney cells in the presence of 32P-phosphoric acid showed that the slightly basic 15000 D protein (pp 15) is the major phosphorylated component of the virus. This result further distinguishes BLV from mammalian type C viruses which possess acidic major phosphorproteins.", "contents": "Proteins of bovine leudemia virus: p. 15 is the major phosphorprotein. Sodium dodecylsulfate-polyacrylamide gel electrophoresis of bovine leukemia virus (BLV) grown in fetal lamb kidney cells in the presence of 32P-phosphoric acid showed that the slightly basic 15000 D protein (pp 15) is the major phosphorylated component of the virus. This result further distinguishes BLV from mammalian type C viruses which possess acidic major phosphorproteins."}
{"id": "PMID:233183", "title": "[Determination and postnatal development of fructokinase activity in swine liver].", "content": "Starting from the spectrophotometric method, described in ADELMAN et al., optimal reaction conditions for the measurement of fructokinase (ketohexokinase) in pig liver were systematically studied. It was necessary to increase the concentration of the substrate and further to lower the concentration of ATP for an optimal Mg: ATP-radio of 2:1. Using the optimized method fructokinase activity was determined in pig liver in relation to age, beginning from the last days of pregnancy to puberty. In liver of fetuses and newborn piglets during the first two days of life no or only a minute activity of the fructokinase was recorded. Therefore, the high level of fructose in fetal blood results from the inability of the fetus to metabolize fructose synthezised in the placenta or the fetal organs. At the end of the first week of life the activity of fructokinase was 10 times, after the second week 15-20 times higher than at birth. This high level remains constant during the suckling period and after weaning. For this reason, piglets after the first week of life are able to metabolize fructose and after the third week to form glucose and to release it into circulation. In adult pigs the activity of fructokinase in the liver decreases slightly. It corresponds-as in rat and human-to the elimination rate of experimentally applied fructose from the circulation. Therefore, this enzyme even in pigs is of significant importance for the utilization of fructose.", "contents": "[Determination and postnatal development of fructokinase activity in swine liver]. Starting from the spectrophotometric method, described in ADELMAN et al., optimal reaction conditions for the measurement of fructokinase (ketohexokinase) in pig liver were systematically studied. It was necessary to increase the concentration of the substrate and further to lower the concentration of ATP for an optimal Mg: ATP-radio of 2:1. Using the optimized method fructokinase activity was determined in pig liver in relation to age, beginning from the last days of pregnancy to puberty. In liver of fetuses and newborn piglets during the first two days of life no or only a minute activity of the fructokinase was recorded. Therefore, the high level of fructose in fetal blood results from the inability of the fetus to metabolize fructose synthezised in the placenta or the fetal organs. At the end of the first week of life the activity of fructokinase was 10 times, after the second week 15-20 times higher than at birth. This high level remains constant during the suckling period and after weaning. For this reason, piglets after the first week of life are able to metabolize fructose and after the third week to form glucose and to release it into circulation. In adult pigs the activity of fructokinase in the liver decreases slightly. It corresponds-as in rat and human-to the elimination rate of experimentally applied fructose from the circulation. Therefore, this enzyme even in pigs is of significant importance for the utilization of fructose."}
{"id": "PMID:233184", "title": "[Dynamic behavior of the adaptive control system, hypothalamus--anterior pituitary--adrenal cortex. Animal experimental study of the adequate system dynamics of the direct and indirect parameters of the adaptive control system].", "content": "The dynamic response of the adaptive closed-loop control system hypothalamus-anterior pituitary-adrenal cortex after application of short-time disturb pulses were examined experimentally in the pig. Blood sampling was performed biologically non-reactive by chronically implanted vascular catheters in the upper vena cava. A circadian biphase periodical dynamics characterizes the distrubance response of the adaptive control system, respectively, its direct and indirect parameters. After distrubance variables induced initial excess the plasma corticosteriods undershoot the basic level over a long period. Conversely, the dynamics of the eosinophils is determined through an initial eosinopenic phase and a subsequent typical overshoot. Periodical dynamic is absent in the steady state. The controller of the adaptive system does not show any spontaneous activity in the steady state without stress. The absence of an endogenic periodicity of the dependent parameters likewise gives evidence of an active oscillator. On the other hand, the controlling unit of the adaptive system constitutes a control response of circadian periodicty after activation by disturbance variables in pulse shape. The high damping of the control system terminates the transient state within 24 hours, and the corticosteriods and the eosinophils reach the steady state level. This control quality of the adaptive control system gains a high importance in the origination of the spontaneous circadian periodicity by corticosteriods and eosinophils and for the biological compensation of exogenous distrubance variables.", "contents": "[Dynamic behavior of the adaptive control system, hypothalamus--anterior pituitary--adrenal cortex. Animal experimental study of the adequate system dynamics of the direct and indirect parameters of the adaptive control system]. The dynamic response of the adaptive closed-loop control system hypothalamus-anterior pituitary-adrenal cortex after application of short-time disturb pulses were examined experimentally in the pig. Blood sampling was performed biologically non-reactive by chronically implanted vascular catheters in the upper vena cava. A circadian biphase periodical dynamics characterizes the distrubance response of the adaptive control system, respectively, its direct and indirect parameters. After distrubance variables induced initial excess the plasma corticosteriods undershoot the basic level over a long period. Conversely, the dynamics of the eosinophils is determined through an initial eosinopenic phase and a subsequent typical overshoot. Periodical dynamic is absent in the steady state. The controller of the adaptive system does not show any spontaneous activity in the steady state without stress. The absence of an endogenic periodicity of the dependent parameters likewise gives evidence of an active oscillator. On the other hand, the controlling unit of the adaptive system constitutes a control response of circadian periodicty after activation by disturbance variables in pulse shape. The high damping of the control system terminates the transient state within 24 hours, and the corticosteriods and the eosinophils reach the steady state level. This control quality of the adaptive control system gains a high importance in the origination of the spontaneous circadian periodicity by corticosteriods and eosinophils and for the biological compensation of exogenous distrubance variables."}
{"id": "PMID:233188", "title": "Sleep, psychophysiological functioning and learning processes in schizophrenia.", "content": "Sleep research has underlined how sleep is a specific functional moment inserted in the more complex system of circadian psychobiological rhythms. Many experimental data have evidenced that in particular REM sleep is involved in information processing and cognitive processes. The authors examine correlations between daytime cognitive performances and sleep patterns in a group of 11 schizophrenic patients, and in a control group made of 11 non-schizophrenic (borderline, depressed, character disorders) patients. Results show that there exists a relationship between REM sleep and cognitive activities, beyond nosographic partitions. They on the other side suggest caution in using sleep as a means of discrimination between schizophrenic and non-schizophrenic patients.", "contents": "Sleep, psychophysiological functioning and learning processes in schizophrenia. Sleep research has underlined how sleep is a specific functional moment inserted in the more complex system of circadian psychobiological rhythms. Many experimental data have evidenced that in particular REM sleep is involved in information processing and cognitive processes. The authors examine correlations between daytime cognitive performances and sleep patterns in a group of 11 schizophrenic patients, and in a control group made of 11 non-schizophrenic (borderline, depressed, character disorders) patients. Results show that there exists a relationship between REM sleep and cognitive activities, beyond nosographic partitions. They on the other side suggest caution in using sleep as a means of discrimination between schizophrenic and non-schizophrenic patients."}
{"id": "PMID:233194", "title": "Electron microscopic examination of skin and conjunctival biopsy specimens in neuronal storage diseases.", "content": "Skin and conjunctival biopsy specimens from fourteen patients with neuronal storage diseases were investigated using an electron microscope. The diseases were Tay-Sachs disease, ceroid-lipofuscinosis (Jansky-Bielschowsky type), Niemann-Pick disease (type B), highly suspected adrenoleukodystrophy, I-cell disease, mucolipidosis of the beta-galactosidase deficient type, Hurler disease, Hunter disease and Morquio disease. This examination provided valuable diagnostic information on some neuronal storage diseases but not on Morquio disease or highly suspected adrenoleukodystrophy. False negative results may sometimes occur using this examination method. However, this examination suggests the usefulness of skin and conjunctival biopsy specimens as a diagnostic tool in some neuronal storage diseases.", "contents": "Electron microscopic examination of skin and conjunctival biopsy specimens in neuronal storage diseases. Skin and conjunctival biopsy specimens from fourteen patients with neuronal storage diseases were investigated using an electron microscope. The diseases were Tay-Sachs disease, ceroid-lipofuscinosis (Jansky-Bielschowsky type), Niemann-Pick disease (type B), highly suspected adrenoleukodystrophy, I-cell disease, mucolipidosis of the beta-galactosidase deficient type, Hurler disease, Hunter disease and Morquio disease. This examination provided valuable diagnostic information on some neuronal storage diseases but not on Morquio disease or highly suspected adrenoleukodystrophy. False negative results may sometimes occur using this examination method. However, this examination suggests the usefulness of skin and conjunctival biopsy specimens as a diagnostic tool in some neuronal storage diseases."}
{"id": "PMID:233197", "title": "[Studies of the presence of enzymes in various tissues of swine. 4. Studies of the Ca-, Mg-, and Na-K-ATPase activities in the homogenate and cell fractions of brain of fetuses and piglets].", "content": "Studies were conducted into the activities of calcium, magnesium, and sodium-potassium ATPase as well as into crude protein levels in homogenate and cell fractions of brain of two foetuses, aged 111 days, and of two piglets each, aged two days or nine weeks. The average brain-borne crude protein percentages were 6.55 in the foetuses, 7.25 in the two-day piglets, and 9.60 in the nine-week piglets. Calcium, magnesium, and sodium-potassium ATPase activities, related to one gram of fresh brain mass, were found to go up along with growing age. Highest relative percentages of sodium-potassium ATPase were recordable from homogenate and from the mitochondrial and microsomal fractions of the foetuses. Certain quantitative differences were obtained from using calcium, magnesium, sodium, and potassium ions to stimulate ATPase in the fractions of cell nuclei, mitochondria, and microsomes. The optimum temperature for magnesium and sodium-potassium ATPase in homogenate and in the mitochondrial fraction of brain was 45 degrees C.", "contents": "[Studies of the presence of enzymes in various tissues of swine. 4. Studies of the Ca-, Mg-, and Na-K-ATPase activities in the homogenate and cell fractions of brain of fetuses and piglets]. Studies were conducted into the activities of calcium, magnesium, and sodium-potassium ATPase as well as into crude protein levels in homogenate and cell fractions of brain of two foetuses, aged 111 days, and of two piglets each, aged two days or nine weeks. The average brain-borne crude protein percentages were 6.55 in the foetuses, 7.25 in the two-day piglets, and 9.60 in the nine-week piglets. Calcium, magnesium, and sodium-potassium ATPase activities, related to one gram of fresh brain mass, were found to go up along with growing age. Highest relative percentages of sodium-potassium ATPase were recordable from homogenate and from the mitochondrial and microsomal fractions of the foetuses. Certain quantitative differences were obtained from using calcium, magnesium, sodium, and potassium ions to stimulate ATPase in the fractions of cell nuclei, mitochondria, and microsomes. The optimum temperature for magnesium and sodium-potassium ATPase in homogenate and in the mitochondrial fraction of brain was 45 degrees C."}
{"id": "PMID:233198", "title": "[Results of histochemical and biochemical studies of uterus of gilts during the estrous cycle].", "content": "Alkaline phosphatase activity as well as lipid, polysaccharide, glycogen, and acid mucopolysaccharide levels in the uteri of 79 gilts were histochemically tested during the first three sexual cycles. Intra-cyclic alkaline phosphatase activity exhibited clearly pronounced variations in the surface epithelium, with maximum values reached in metoestrus, and moderate variations in the endometrial stroma, with maximum values reached in dioestrus. Cycle-dependent variations were recordable also from the glycogen and lipid levels in the surface and glandular epithelia and from the acid mucopolysaccharide levels in the endometrial stroma. The activity of alkaline phosphatase as well as the levels of glycogen and acid mucopolysaccharides during the first cycle still were lower than those in the second and third. Biochemical examinations of the endometrium revealed significant cycle-dependent variations in the activities of alkaline phosphatase, inorganic pyrophosphatase, and succinate-dehydrogenase as well as in the concentrations of soluble protein and glycogen, with maximum values being recordable on the tenth day of cycle. No significant intracyclic variations were recordable from the activities of acid phosphatase as well as of aspartate alanine-amino transferase.", "contents": "[Results of histochemical and biochemical studies of uterus of gilts during the estrous cycle]. Alkaline phosphatase activity as well as lipid, polysaccharide, glycogen, and acid mucopolysaccharide levels in the uteri of 79 gilts were histochemically tested during the first three sexual cycles. Intra-cyclic alkaline phosphatase activity exhibited clearly pronounced variations in the surface epithelium, with maximum values reached in metoestrus, and moderate variations in the endometrial stroma, with maximum values reached in dioestrus. Cycle-dependent variations were recordable also from the glycogen and lipid levels in the surface and glandular epithelia and from the acid mucopolysaccharide levels in the endometrial stroma. The activity of alkaline phosphatase as well as the levels of glycogen and acid mucopolysaccharides during the first cycle still were lower than those in the second and third. Biochemical examinations of the endometrium revealed significant cycle-dependent variations in the activities of alkaline phosphatase, inorganic pyrophosphatase, and succinate-dehydrogenase as well as in the concentrations of soluble protein and glycogen, with maximum values being recordable on the tenth day of cycle. No significant intracyclic variations were recordable from the activities of acid phosphatase as well as of aspartate alanine-amino transferase."}
{"id": "PMID:233201", "title": "[Circadian rhythm of poly A polymerase in rat liver nuclei].", "content": "Isolated nuclei from the liver of rats maintained under daily scheduled conditions of light (12 hrs) and food (8 hrs) showed a peak of Mn2+-dependent poly (A) polymerase activity 6 hrs after the beginning of the feeding period, as shown by DNA dependent RNA polymerase B. In fasting animals the peak of poly (A) polymerase occurs at 18.00.", "contents": "[Circadian rhythm of poly A polymerase in rat liver nuclei]. Isolated nuclei from the liver of rats maintained under daily scheduled conditions of light (12 hrs) and food (8 hrs) showed a peak of Mn2+-dependent poly (A) polymerase activity 6 hrs after the beginning of the feeding period, as shown by DNA dependent RNA polymerase B. In fasting animals the peak of poly (A) polymerase occurs at 18.00."}
{"id": "PMID:233202", "title": "[Circadian rhythm of poly A polymerase in chromatin and nucleoplasmatic extract of rat liver].", "content": "Chromatin preparations from the liver of rats accustomed to eating during the first 8 hrs of a daily 12 hrs dark period exhibit the same fluctuations of poly (A) polymerase as whole nuclei (a peak at 15.00 in fed rats, a peak at 18.00 in fasting ones). Nucleoplasmic activity was detectable only on addition of exogenous primer.", "contents": "[Circadian rhythm of poly A polymerase in chromatin and nucleoplasmatic extract of rat liver]. Chromatin preparations from the liver of rats accustomed to eating during the first 8 hrs of a daily 12 hrs dark period exhibit the same fluctuations of poly (A) polymerase as whole nuclei (a peak at 15.00 in fed rats, a peak at 18.00 in fasting ones). Nucleoplasmic activity was detectable only on addition of exogenous primer."}
{"id": "PMID:233199", "title": "[Treatment of swine cell line with antibiotics: effect on growth kinetics and susceptibility to foot-and-mouth disease virus and to mycoplasma-like organisms].", "content": "Cell cultures treated with tylosin tartrate and kanamycin sulphate antibiotics were studied in relation to the cell growth rate, the susceptibility to the foot-and-mouth disease virus and to the microorganism eradication. These treatments did not affect the cell growth rate and the cell behavior to the viral infection. On the other hand, the decontamination of the intracytoplasmatic formas of mycoplasma-like organism was not observed.", "contents": "[Treatment of swine cell line with antibiotics: effect on growth kinetics and susceptibility to foot-and-mouth disease virus and to mycoplasma-like organisms]. Cell cultures treated with tylosin tartrate and kanamycin sulphate antibiotics were studied in relation to the cell growth rate, the susceptibility to the foot-and-mouth disease virus and to the microorganism eradication. These treatments did not affect the cell growth rate and the cell behavior to the viral infection. On the other hand, the decontamination of the intracytoplasmatic formas of mycoplasma-like organism was not observed."}
{"id": "PMID:233203", "title": "[Effect of various methods of preparation of chromatin on the distribution of Mn2+-dependent poly-A-polymerase activity in subnuclear fractions of rat liver].", "content": "The distribution of Mn2+-dependent poly(A) polymerase activity between chromatin and nucleoplasmic fractions in rat liver nuclei strongly depends on the method followed for the chromatin preparation. Currently used methods containing high salt cause a loss in bound activity not accompanied by a correspondent increase in the \"free\" one.", "contents": "[Effect of various methods of preparation of chromatin on the distribution of Mn2+-dependent poly-A-polymerase activity in subnuclear fractions of rat liver]. The distribution of Mn2+-dependent poly(A) polymerase activity between chromatin and nucleoplasmic fractions in rat liver nuclei strongly depends on the method followed for the chromatin preparation. Currently used methods containing high salt cause a loss in bound activity not accompanied by a correspondent increase in the \"free\" one."}
{"id": "PMID:233200", "title": "[Isolation of bovine cell lines and susceptibility to foot-and-mouth disease virus].", "content": "Morphology and chromosomes of cell sublines derived from two new bovine kidney lines are reported. Cell susceptibility to the foot-and-mouth disease virus is discussed. One of the sublines showed epithelial-like cells, while the remainder, elonged fibroblastic-like cells. Most of them had a diploid number of chromosomes. From these sublines only one was sensible to the foot-and-mouth disease virus.", "contents": "[Isolation of bovine cell lines and susceptibility to foot-and-mouth disease virus]. Morphology and chromosomes of cell sublines derived from two new bovine kidney lines are reported. Cell susceptibility to the foot-and-mouth disease virus is discussed. One of the sublines showed epithelial-like cells, while the remainder, elonged fibroblastic-like cells. Most of them had a diploid number of chromosomes. From these sublines only one was sensible to the foot-and-mouth disease virus."}
{"id": "PMID:233204", "title": "[Effect of administration of alpha-amanitine on Mn2+ - dependent poly-A-polymerase in rat liver nuclei].", "content": "Mn2+-dependent poly(A) polymerase activity tested in isolated rat liver nuclei is unchanged both in the absence and presence of exogenous poly(A) 30 min. after administration of a dose of alpha-amanitin that inhibits DNA-dependent RNA polymerase B. Longer times of treatment cause poly(A) polymerase to drop to 50% in the absence of poly(A) and to increase almost twice in its presence.", "contents": "[Effect of administration of alpha-amanitine on Mn2+ - dependent poly-A-polymerase in rat liver nuclei]. Mn2+-dependent poly(A) polymerase activity tested in isolated rat liver nuclei is unchanged both in the absence and presence of exogenous poly(A) 30 min. after administration of a dose of alpha-amanitin that inhibits DNA-dependent RNA polymerase B. Longer times of treatment cause poly(A) polymerase to drop to 50% in the absence of poly(A) and to increase almost twice in its presence."}
{"id": "PMID:233208", "title": "Hydrocephalus-dementia-complex in Paget's disease.", "content": "The clinical triad of gait disturbances, memory impairment and urinary incontinence is associated with a communicating hydrocephalus in the 'normal pressure hydrocephalus'-syndrome. The authors present a case of H.D.C. (hydrocephalus-dementia-complex) in Paget's disease with an identical syndrome, but with obstructive hydrocephalus, causing a triventricular dilatation. Today, each case of mental deterioration in Paget's disease, should be immediately observed and neurosurgical intervention kept in view. An X-ray of the skull, a CT-scan of the brain and a cisternography are performed as routine procedure. If there are indications of involvement of the basis of the skull, hydrocephalus and/or disturbed pattern of the tracer-migration around the convexities, associated with a certain degree of dementia, impaired gait or urinary incontinence, a ventriculo-subcutaneous drain should be inserted. If clinical improvement follows, a ventriculatrial shunt is indicated. The post-operative clinical outcome seems to be dependent on some clinical and technical factors. The most eventful outcome is observed in cases where the clinial triad, described in patients with a classical 'normal pressure hydrocephalus'-syndrome, is associated with an obstructive hydrocephalus, due to a stenosis of the Sylvian aqueduct.", "contents": "Hydrocephalus-dementia-complex in Paget's disease. The clinical triad of gait disturbances, memory impairment and urinary incontinence is associated with a communicating hydrocephalus in the 'normal pressure hydrocephalus'-syndrome. The authors present a case of H.D.C. (hydrocephalus-dementia-complex) in Paget's disease with an identical syndrome, but with obstructive hydrocephalus, causing a triventricular dilatation. Today, each case of mental deterioration in Paget's disease, should be immediately observed and neurosurgical intervention kept in view. An X-ray of the skull, a CT-scan of the brain and a cisternography are performed as routine procedure. If there are indications of involvement of the basis of the skull, hydrocephalus and/or disturbed pattern of the tracer-migration around the convexities, associated with a certain degree of dementia, impaired gait or urinary incontinence, a ventriculo-subcutaneous drain should be inserted. If clinical improvement follows, a ventriculatrial shunt is indicated. The post-operative clinical outcome seems to be dependent on some clinical and technical factors. The most eventful outcome is observed in cases where the clinial triad, described in patients with a classical 'normal pressure hydrocephalus'-syndrome, is associated with an obstructive hydrocephalus, due to a stenosis of the Sylvian aqueduct."}
{"id": "PMID:233209", "title": "Bilirubin excess, erythrophages and siderophages in differentiation of blood in cerebrospinal fluid.", "content": "Non-artificial blood admixture in cerebrospinal fluid (CSF) can be proven by demonstrating siderophages and 'bilirubin excess'. Bilirubin excess exists when the bilirubin concentration measured in the CSF exceeds the expected CSF bilirubin concentration. The expected CSF bilirubin concentration is calculated by multiplying the serum bilirubin concentration by the albumin quotient. Given a certain method of determination, a difference between the above-mentioned concentrations of less than 0.15 mumol/l must not be regarded as excess. Bilirubin excess was exclusively found in CSF with non-artificial blood admixture. Cytological and spectrophotometric studies are sufficient in screening for non-artificial blood admixture. When there are indications of an increased bilirubin concentration, calculations should be made in order to establish whether bilirubin excess exists. Lumbar puncture within 48 hours of the suspected haemorrhage should be avoided if possible.", "contents": "Bilirubin excess, erythrophages and siderophages in differentiation of blood in cerebrospinal fluid. Non-artificial blood admixture in cerebrospinal fluid (CSF) can be proven by demonstrating siderophages and 'bilirubin excess'. Bilirubin excess exists when the bilirubin concentration measured in the CSF exceeds the expected CSF bilirubin concentration. The expected CSF bilirubin concentration is calculated by multiplying the serum bilirubin concentration by the albumin quotient. Given a certain method of determination, a difference between the above-mentioned concentrations of less than 0.15 mumol/l must not be regarded as excess. Bilirubin excess was exclusively found in CSF with non-artificial blood admixture. Cytological and spectrophotometric studies are sufficient in screening for non-artificial blood admixture. When there are indications of an increased bilirubin concentration, calculations should be made in order to establish whether bilirubin excess exists. Lumbar puncture within 48 hours of the suspected haemorrhage should be avoided if possible."}
{"id": "PMID:233210", "title": "Radiotherapy in brain-stem gliomas in children.", "content": "Twenty-one children with brain-stem glioma are discussed. Sixteen received radiotherapy and five were too sick to be irradiated. The mean survival was 3.4 weeks for the non-irradiated group and 8.7 months for the treated group, two of the latter being still alive five and ten months after diagnosis. From the literature and our cases the effect of radiotherapy in brain-stem glioma in childhood is not clear. Differences in patient-selection criteria and the mode and doses of irradiation between the reported series may account for the divergent results, but in our cases radiotherapy did not prolong survival as significantly as compared with the reported series. Elevated intracranial pressure is not rare in patients with a brain-stem glioma, as may be concluded from the present series and from the literature.", "contents": "Radiotherapy in brain-stem gliomas in children. Twenty-one children with brain-stem glioma are discussed. Sixteen received radiotherapy and five were too sick to be irradiated. The mean survival was 3.4 weeks for the non-irradiated group and 8.7 months for the treated group, two of the latter being still alive five and ten months after diagnosis. From the literature and our cases the effect of radiotherapy in brain-stem glioma in childhood is not clear. Differences in patient-selection criteria and the mode and doses of irradiation between the reported series may account for the divergent results, but in our cases radiotherapy did not prolong survival as significantly as compared with the reported series. Elevated intracranial pressure is not rare in patients with a brain-stem glioma, as may be concluded from the present series and from the literature."}
{"id": "PMID:233214", "title": "Why should we study the infant 'near miss for Sudden Infant Death'?", "content": "The use of 'near miss for Sudden Infant Death syndrome' infants as a model toward understanding the Sudden Infant Death syndrome has been questioned. Although there are numerous problems in delineating this patient population and defining events occurring during sleep, continuous polygraphic monitoring demonstrates potentially life-threatening events.", "contents": "Why should we study the infant 'near miss for Sudden Infant Death'? The use of 'near miss for Sudden Infant Death syndrome' infants as a model toward understanding the Sudden Infant Death syndrome has been questioned. Although there are numerous problems in delineating this patient population and defining events occurring during sleep, continuous polygraphic monitoring demonstrates potentially life-threatening events."}
{"id": "PMID:233216", "title": "Relationship between prostaglandins and cyclic-AMP in the process of implantation in rats.", "content": "The effect of alloxan, a known inhibitor of adenylate cyclase, on the levels of prostaglandins E and F was investigated in pregnant rats. Animals were treated intraluminally with alloxan in normal saline or alloxan plus cyclic-AMP in normal saline or normal saline alone on day 4 of pregnancy. The uteri were collected on days 5 and 6 of pregnancy and the prostaglandins E and F were extracted and measured by a radioimmunoassay technique. In the alloxan treated rats, a significant reduction in PGE and PGF levels was found on days 5 and 6 of pregnancy as compared to untreated control group, whereas in the alloxan plus cyclic-AMP treated group the levels of PGE and PGF were comparable to those of the untreated control group. These findings suggest a possible relationship between prostaglandins and cyclic-AMP in the process of implantation in rats.", "contents": "Relationship between prostaglandins and cyclic-AMP in the process of implantation in rats. The effect of alloxan, a known inhibitor of adenylate cyclase, on the levels of prostaglandins E and F was investigated in pregnant rats. Animals were treated intraluminally with alloxan in normal saline or alloxan plus cyclic-AMP in normal saline or normal saline alone on day 4 of pregnancy. The uteri were collected on days 5 and 6 of pregnancy and the prostaglandins E and F were extracted and measured by a radioimmunoassay technique. In the alloxan treated rats, a significant reduction in PGE and PGF levels was found on days 5 and 6 of pregnancy as compared to untreated control group, whereas in the alloxan plus cyclic-AMP treated group the levels of PGE and PGF were comparable to those of the untreated control group. These findings suggest a possible relationship between prostaglandins and cyclic-AMP in the process of implantation in rats."}
{"id": "PMID:233217", "title": "Thromboxane B2: a cardiodepressant of isolated rat hearts and inhibitor of sarcolemma Na+ - K+ stimulated ATPase activity.", "content": "The actions of thromboxane B2 on various parameters of cardiac performance were studied using the isolated perfused rat heart model. In concentrations from 100 pg/ml to 1 microgram/ml TXB2 significantly reduced the total generated myocardial contractile force. These changes were usually associated with an increase in the coronary perfusion pressure indicating an elevated coronary vascular resitance. Significant coronary pressure alterations were seen with TXB2 concentrations between 1 ng/ml and 1 microgram/ml. No significant changes were seen in either the resting tension or heart rate after TXB2 administration. However TXB2 (10 pg/ml to 10 ng/ml,, significantly reduced the amplitude of the electrical activity as observed in R wave changes of the surface electrocardiogram recording. In another series of experiments the action of TXB2 on rat heart sarcolemmal ATPase activity was studied. TXB2 significantly reduced the activity of the MG++ dependent - Na+ - K+ stimulated ATPase (Na+ - K+ ATPase) in these membrane preparations in concentrations from 10 ng/ml to 1 microgram/ml. Kinetic studies demonstrated that TXB2 reduced Vmax and increased the concentration required of ATP, Na+ and K+ for half-maximal enzyme activity. TXB2 did not inhibit either Ca++ or ouabain-induced depression of Na+ - K+ ATPase activity. The activity of either Mg++ or Ca++ - stimulated ATPase was not affected by TXB2. These results suggest possible important actions of TXB2 on rat heart activity which may be related to Na+ - K+ ATPase inhibition.", "contents": "Thromboxane B2: a cardiodepressant of isolated rat hearts and inhibitor of sarcolemma Na+ - K+ stimulated ATPase activity. The actions of thromboxane B2 on various parameters of cardiac performance were studied using the isolated perfused rat heart model. In concentrations from 100 pg/ml to 1 microgram/ml TXB2 significantly reduced the total generated myocardial contractile force. These changes were usually associated with an increase in the coronary perfusion pressure indicating an elevated coronary vascular resitance. Significant coronary pressure alterations were seen with TXB2 concentrations between 1 ng/ml and 1 microgram/ml. No significant changes were seen in either the resting tension or heart rate after TXB2 administration. However TXB2 (10 pg/ml to 10 ng/ml,, significantly reduced the amplitude of the electrical activity as observed in R wave changes of the surface electrocardiogram recording. In another series of experiments the action of TXB2 on rat heart sarcolemmal ATPase activity was studied. TXB2 significantly reduced the activity of the MG++ dependent - Na+ - K+ stimulated ATPase (Na+ - K+ ATPase) in these membrane preparations in concentrations from 10 ng/ml to 1 microgram/ml. Kinetic studies demonstrated that TXB2 reduced Vmax and increased the concentration required of ATP, Na+ and K+ for half-maximal enzyme activity. TXB2 did not inhibit either Ca++ or ouabain-induced depression of Na+ - K+ ATPase activity. The activity of either Mg++ or Ca++ - stimulated ATPase was not affected by TXB2. These results suggest possible important actions of TXB2 on rat heart activity which may be related to Na+ - K+ ATPase inhibition."}
{"id": "PMID:233218", "title": "Effect of prostaglandins on the increased corticosterone output induced by caffeine in the rat.", "content": "The effect of prostaglandins on the increase of corticosterone output induced by caffeine was investigated in rats. PGE2 and some synthetic prostaglandins (11-deoxy-derivatives), which stimulate steroid output in vitro, enhanced the effect of caffeine. Pretreatment with indomethacin inhibited the effect of caffeine.", "contents": "Effect of prostaglandins on the increased corticosterone output induced by caffeine in the rat. The effect of prostaglandins on the increase of corticosterone output induced by caffeine was investigated in rats. PGE2 and some synthetic prostaglandins (11-deoxy-derivatives), which stimulate steroid output in vitro, enhanced the effect of caffeine. Pretreatment with indomethacin inhibited the effect of caffeine."}
{"id": "PMID:233219", "title": "Antibody dependent cell-mediated cytotoxicity to herpes simplex virus in man: the influence of drugs on polymorphonuclear leucocyte and mononuclear effector cells.", "content": "We have shown that the function of the effector cells in antibody mediated cell dependent cytotoxicity (ADCC) can be reduced by the use of a number of drugs and prostaglandins. Both polymorphonuclear leucocyte and mononuclear effector cells were studied. Aminophylline and isoproterenol markedly reduced this activity. All the prostaglandins tested--PGA1, A2, E1 and E2 had a similar but more profound effect. At a dose of 100 mg/ml hydrocortisone had relatively little influence and neither ASA nor indomethacin had any effect on the effector cells tested. It is suggested that the effect of PGE1 in stimulating a recrudescent herpes simplex infection may be by reducing the efficacy of ADCC in host defence.", "contents": "Antibody dependent cell-mediated cytotoxicity to herpes simplex virus in man: the influence of drugs on polymorphonuclear leucocyte and mononuclear effector cells. We have shown that the function of the effector cells in antibody mediated cell dependent cytotoxicity (ADCC) can be reduced by the use of a number of drugs and prostaglandins. Both polymorphonuclear leucocyte and mononuclear effector cells were studied. Aminophylline and isoproterenol markedly reduced this activity. All the prostaglandins tested--PGA1, A2, E1 and E2 had a similar but more profound effect. At a dose of 100 mg/ml hydrocortisone had relatively little influence and neither ASA nor indomethacin had any effect on the effector cells tested. It is suggested that the effect of PGE1 in stimulating a recrudescent herpes simplex infection may be by reducing the efficacy of ADCC in host defence."}
{"id": "PMID:233220", "title": "Secretory effect of prostaglandins on the rabbit lacrimal gland in vivo.", "content": "Fluid secretion from the cannulated excretory duct of the rabbit lacrimal gland was collected in microcapillary pipette at 10 min intervals. Secretion rate and electrolyte concentrations (Na+, K+ and Cl-) in the lacrimal fluid samples were determined before and after injections of small doses of prostaglandins (PGE1, PGE2, PGF1 alpha, PGF2 alpha, 15 epi-PGF2 alpha, PGF2 beta, PGA1 & PGA2) into the external maxillary artery. Only PGE1 had a dose-dependent stimulatory effect on the lacrimal gland secretion. The maximum secretion rate which was induced by PGE1 (25 micrograms/kg) was 7.2 +/- 0.9 microliters/10 min. Na+ concentration in the fluid secretion stimulated by PGE1 was increased; however, K+ and Cl- concentrations were not changed. Pretreatment with atropine (50 micrograms/kg, I.A.) failed to prevent the stimulatory effect of low doses of PGE1. On the other hand, the secretory responses were abolished when propanolol (3 mg/kg, I.A.) was administered prior to PGE1. The results suggest that fluid secretion of the rabbit lacrimal gland in response to PGE1 may be caused by excitation of the sympathetic ganglia and/or by direct action on beta-receptors in the acinar cells.", "contents": "Secretory effect of prostaglandins on the rabbit lacrimal gland in vivo. Fluid secretion from the cannulated excretory duct of the rabbit lacrimal gland was collected in microcapillary pipette at 10 min intervals. Secretion rate and electrolyte concentrations (Na+, K+ and Cl-) in the lacrimal fluid samples were determined before and after injections of small doses of prostaglandins (PGE1, PGE2, PGF1 alpha, PGF2 alpha, 15 epi-PGF2 alpha, PGF2 beta, PGA1 & PGA2) into the external maxillary artery. Only PGE1 had a dose-dependent stimulatory effect on the lacrimal gland secretion. The maximum secretion rate which was induced by PGE1 (25 micrograms/kg) was 7.2 +/- 0.9 microliters/10 min. Na+ concentration in the fluid secretion stimulated by PGE1 was increased; however, K+ and Cl- concentrations were not changed. Pretreatment with atropine (50 micrograms/kg, I.A.) failed to prevent the stimulatory effect of low doses of PGE1. On the other hand, the secretory responses were abolished when propanolol (3 mg/kg, I.A.) was administered prior to PGE1. The results suggest that fluid secretion of the rabbit lacrimal gland in response to PGE1 may be caused by excitation of the sympathetic ganglia and/or by direct action on beta-receptors in the acinar cells."}
{"id": "PMID:233224", "title": "[Diagnostic value of serum angiotensin converting enzyme activity in sarcoidosis (author's transl)].", "content": "Serum angiotensin converting enzyme activity was measured in 60 blood donors and 100 patients with sarcoidosis histologically confirmed using a spectrophotometric assay with hippurylhistidylleucine as substrate. Sex related differences in the enzyme activity could not be observed. ACE was found to be markedly raised above the normal range (the mean of the control subjects plus 2 standard deviations) in 53 (58.2%) out of 91 untreated patients. The distribution of the enzyme activities was significantly different as compared to the control group. Nine patients with sarcoidosis receiving steroids had a mean level within the normal range. ACE level in stage II group tended to be more elevated compared to stage I, but this difference was not significant. Extrapulmonary sarcoidosis (with and without pulmonary involvement) appeared to be associated with especially high ACE activities. The distribution of the enzyme activities within the groups of untreated patients failed to reveal statistically significant differences. Therefore it was not possible to determine the clinical state of the disease and to discriminate between the stages (I and II) of sarcoidosis by the measurement of serum ACE level. However as the results suggest serum ACE assays can be a useful aid in diagnosis of sarcoidosis. Further investigations may demonstrate the value of this in vitro method for the clinical management of the disease including prognosis and therapeutic effects.", "contents": "[Diagnostic value of serum angiotensin converting enzyme activity in sarcoidosis (author's transl)]. Serum angiotensin converting enzyme activity was measured in 60 blood donors and 100 patients with sarcoidosis histologically confirmed using a spectrophotometric assay with hippurylhistidylleucine as substrate. Sex related differences in the enzyme activity could not be observed. ACE was found to be markedly raised above the normal range (the mean of the control subjects plus 2 standard deviations) in 53 (58.2%) out of 91 untreated patients. The distribution of the enzyme activities was significantly different as compared to the control group. Nine patients with sarcoidosis receiving steroids had a mean level within the normal range. ACE level in stage II group tended to be more elevated compared to stage I, but this difference was not significant. Extrapulmonary sarcoidosis (with and without pulmonary involvement) appeared to be associated with especially high ACE activities. The distribution of the enzyme activities within the groups of untreated patients failed to reveal statistically significant differences. Therefore it was not possible to determine the clinical state of the disease and to discriminate between the stages (I and II) of sarcoidosis by the measurement of serum ACE level. However as the results suggest serum ACE assays can be a useful aid in diagnosis of sarcoidosis. Further investigations may demonstrate the value of this in vitro method for the clinical management of the disease including prognosis and therapeutic effects."}
{"id": "PMID:233225", "title": "Self-mutilation and sleep stage in the Lesch-Nyhan syndrome.", "content": "Correlation of self-mutilation and sleep stage in the Lesch-Nyhan syndrome was studied by a polygraphic method. Five patients and three control boys were monitored with EEG, EOG, EMG, ECG and respiration throughout the night. The results were as follows: 1. The sleep-time of the patients was much disturbed during the night. 2. Decreased REM density was noticed with low DQ of the patients. 3. Self-mutilation during sleep-time was observed a lot in stages 1, 2, and REM in two cases. 4. No correlation was observed between body movement and self-mutilation in the Lesch-Nyhan syndrome. These data suggested functional disorders of the frontal lobe in the patients.", "contents": "Self-mutilation and sleep stage in the Lesch-Nyhan syndrome. Correlation of self-mutilation and sleep stage in the Lesch-Nyhan syndrome was studied by a polygraphic method. Five patients and three control boys were monitored with EEG, EOG, EMG, ECG and respiration throughout the night. The results were as follows: 1. The sleep-time of the patients was much disturbed during the night. 2. Decreased REM density was noticed with low DQ of the patients. 3. Self-mutilation during sleep-time was observed a lot in stages 1, 2, and REM in two cases. 4. No correlation was observed between body movement and self-mutilation in the Lesch-Nyhan syndrome. These data suggested functional disorders of the frontal lobe in the patients."}
{"id": "PMID:233227", "title": "Pilot sero-epidemiological survey on Japanese encephalitis in north-western Burma.", "content": "A pilot sero-epidemiological survey of Japanese encephalitis was carried out in three areas of north-western Burma applying the hemagglutination-inhibition test. The existence of Japanese encephalitis infection in these areas was confirmed and its incidences in these areas were estimated and compared graphically.", "contents": "Pilot sero-epidemiological survey on Japanese encephalitis in north-western Burma. A pilot sero-epidemiological survey of Japanese encephalitis was carried out in three areas of north-western Burma applying the hemagglutination-inhibition test. The existence of Japanese encephalitis infection in these areas was confirmed and its incidences in these areas were estimated and compared graphically."}
{"id": "PMID:233228", "title": "Demonstration of cells with Marek's disease tumor-associated surface antigen in chicks infected with herpesvirus of turkey, O1 strain.", "content": "The presence of Marek's disease tumor-associated surface antigen (MATSA) was demonstrated by the direct and indirect membrane immunofluorescent tests, in chicks inoculated 7-10 days earlier with herpesvirus of turkeys (HVT), O1 strain. In in vitro cultures of spleen lymphocytes and ovaries obtained from these chicks, MATSA-positive cells were also detected after 1-7 days cultivation. A possible mechanism of protection by HVT vaccine against Marek's disease is proposed.", "contents": "Demonstration of cells with Marek's disease tumor-associated surface antigen in chicks infected with herpesvirus of turkey, O1 strain. The presence of Marek's disease tumor-associated surface antigen (MATSA) was demonstrated by the direct and indirect membrane immunofluorescent tests, in chicks inoculated 7-10 days earlier with herpesvirus of turkeys (HVT), O1 strain. In in vitro cultures of spleen lymphocytes and ovaries obtained from these chicks, MATSA-positive cells were also detected after 1-7 days cultivation. A possible mechanism of protection by HVT vaccine against Marek's disease is proposed."}
{"id": "PMID:233236", "title": "Photokinetic microassay of adenylate kinase using the firefly luciferase reaction.", "content": "A new rapid photokinetic method is described for determining the activity of adenylate kinase (ATP:AMP phosphotranspherase, EC 2.7.4.3) in 0.1--5.0 micrograms of freeze-dried tissue. This represents a weight range far below that obtainable by fine-needle biopsy. The reaction 2 ADP in equilibrium with AMP + ATP was employed and the ATP formed assayed with firefly luciferase as light yielder. The light emission was recorded on a multi-channel scaler. The adenylate kinase activities found in tissues of mice were in the same range as previously described in a study using fluorometric microassay.", "contents": "Photokinetic microassay of adenylate kinase using the firefly luciferase reaction. A new rapid photokinetic method is described for determining the activity of adenylate kinase (ATP:AMP phosphotranspherase, EC 2.7.4.3) in 0.1--5.0 micrograms of freeze-dried tissue. This represents a weight range far below that obtainable by fine-needle biopsy. The reaction 2 ADP in equilibrium with AMP + ATP was employed and the ATP formed assayed with firefly luciferase as light yielder. The light emission was recorded on a multi-channel scaler. The adenylate kinase activities found in tissues of mice were in the same range as previously described in a study using fluorometric microassay."}
{"id": "PMID:233237", "title": "The measurement of subnanosecond fluorescence decay of flavins using time-correlated photon counting and a mode-locked Ar ion laser.", "content": "A system is described consisting of a mode-locked Ar ion laser and time-resolved photon-counting electronics. The system is capable of measuring fluorescence lifetimes in the subnanosecond time domain. The Ar ion laser is suitable for the excitation of flavins, since the available laser wavelengths encompass the first absorption band of the yellow chromophore. Due to the high radiation density and the short pulse, both the time and wavelength resolution of the fluorescence of very weakly emitting compounds can be measured. Experiments have been described for flavin models exhibiting single and multiple modes of decay. In these examples lifetimes were determined both from deconvolved decay curves and from direct analysis of the tail of the curve, where no interference of the exciting pulse is encountered. Both determinations showed very good agreement. Due to the highly polarized laser light the decay of the emission anisotropy could be measured directly after the exciting pulse. In principle, fast rotational motions might be detected. An anisotropy measurement conducted with a flavoprotein with a noncovalently attached FAD is presented.", "contents": "The measurement of subnanosecond fluorescence decay of flavins using time-correlated photon counting and a mode-locked Ar ion laser. A system is described consisting of a mode-locked Ar ion laser and time-resolved photon-counting electronics. The system is capable of measuring fluorescence lifetimes in the subnanosecond time domain. The Ar ion laser is suitable for the excitation of flavins, since the available laser wavelengths encompass the first absorption band of the yellow chromophore. Due to the high radiation density and the short pulse, both the time and wavelength resolution of the fluorescence of very weakly emitting compounds can be measured. Experiments have been described for flavin models exhibiting single and multiple modes of decay. In these examples lifetimes were determined both from deconvolved decay curves and from direct analysis of the tail of the curve, where no interference of the exciting pulse is encountered. Both determinations showed very good agreement. Due to the highly polarized laser light the decay of the emission anisotropy could be measured directly after the exciting pulse. In principle, fast rotational motions might be detected. An anisotropy measurement conducted with a flavoprotein with a noncovalently attached FAD is presented."}
{"id": "PMID:233238", "title": "Small-scale techniques for the analysis of recombinant plasmids.", "content": "Using the cloning of part of the T-DNA of pTiC58 from Agrobacterium tumefaciens as an example, techniques are described which enable recombinant plasmids to be mapped and used as hybridization probes. In all cases the starting material is a colony of cells grown on an agar plate which is then subjected to lysis by lysozyme and Triton X-100 in volumes of the order of 300 microliters thus eliminating the need for handling and centrifuging liquid cultures under restrictive containment conditions.", "contents": "Small-scale techniques for the analysis of recombinant plasmids. Using the cloning of part of the T-DNA of pTiC58 from Agrobacterium tumefaciens as an example, techniques are described which enable recombinant plasmids to be mapped and used as hybridization probes. In all cases the starting material is a colony of cells grown on an agar plate which is then subjected to lysis by lysozyme and Triton X-100 in volumes of the order of 300 microliters thus eliminating the need for handling and centrifuging liquid cultures under restrictive containment conditions."}
{"id": "PMID:233253", "title": "Iatrogenic nondiabetic hyperosmolar states.", "content": "Four cases of the iatrogenic nondiabetic hyperosmolar state are presented. The clinical presentation, biochemical findings and management are discussed. No hypertonic solution should be infused at a rate above the level of patient tolerance; irrigation of a hollow viscus with a hypertonic solution should be avoided, and salt should not be used as an emetic. Patients under stress are particularly prone to this condition, largely because of the high circulating cortisol levels. The use of corticosteroids, salt-containing solutions in excess of patient requirements, water depletion and intravenous nutrition in the absence of careful biochemical monitoring, are all factors which may precipitate the hyperosmolar state in the critically ill.", "contents": "Iatrogenic nondiabetic hyperosmolar states. Four cases of the iatrogenic nondiabetic hyperosmolar state are presented. The clinical presentation, biochemical findings and management are discussed. No hypertonic solution should be infused at a rate above the level of patient tolerance; irrigation of a hollow viscus with a hypertonic solution should be avoided, and salt should not be used as an emetic. Patients under stress are particularly prone to this condition, largely because of the high circulating cortisol levels. The use of corticosteroids, salt-containing solutions in excess of patient requirements, water depletion and intravenous nutrition in the absence of careful biochemical monitoring, are all factors which may precipitate the hyperosmolar state in the critically ill."}
{"id": "PMID:233257", "title": "Mechanism of beta-adrenergic relaxation of smooth muscle.", "content": "The mechanism of beta-adrenergic relaxation was investigated in isolated smooth muscle cells. Beta-adrenergic agents stimulate cyclic AMP-dependent phosphorylation, enhance Na+/K+ transport and induce relaxation. The stimulation of Na+/K+ transport is obligatory for relaxation, and we suggest that this stimulation induces relaxation through enhanced Na+/Ca2+ exchange.", "contents": "Mechanism of beta-adrenergic relaxation of smooth muscle. The mechanism of beta-adrenergic relaxation was investigated in isolated smooth muscle cells. Beta-adrenergic agents stimulate cyclic AMP-dependent phosphorylation, enhance Na+/K+ transport and induce relaxation. The stimulation of Na+/K+ transport is obligatory for relaxation, and we suggest that this stimulation induces relaxation through enhanced Na+/Ca2+ exchange."}
{"id": "PMID:233264", "title": "Hormonal regulation of peptide receptors and target cell responses.", "content": "Regulation of plasma membrane receptors for peptide hormones by the prevailing ligand concentration often causes altered target cell function. Receptor number is determined by hormone-induced changes in membrane conformation, irreversible ligand binding, and processing of ligand-receptor complexes during hormone action.", "contents": "Hormonal regulation of peptide receptors and target cell responses. Regulation of plasma membrane receptors for peptide hormones by the prevailing ligand concentration often causes altered target cell function. Receptor number is determined by hormone-induced changes in membrane conformation, irreversible ligand binding, and processing of ligand-receptor complexes during hormone action."}
{"id": "PMID:233266", "title": "Preoperative cell-mediated immune status of patients with malignant glial tumors.", "content": "The leukocyte adherence inhibition assay (LAI) was used to measure cell-mediated immunity in 26 patients with malignant glial neoplasms and in 41 control subjects. A significant inhibition of leukocyte adherence was observed in 21 out of 26 (80%) patients with malignant astrocytic gliomas in the presence of a 3M KC1 extract of glioma tissue compared to that of normal brain extract. Among the control group, no significant difference in the percentage of nonadherent leukocytes (NAL) was noted in the presence of either antigen. To study the specificity of the reaction, 3M KC1 extracts of meningioma, pituitary tumor, carcinoma of breast, carcinomas of lung, melanoma, brain, and heart tissues were employed as non-specific antigens. Such studies revealed significantly lower values of NAL. These data indicate that patients with malignant glial neoplasms manifest a cellularimmune response to glioma-associated antigens that can be measured by the tube LAI assay and that LAI assay may render additional useful information in the diagnostic and prognostic evaluation of malignant glial neoplasms.", "contents": "Preoperative cell-mediated immune status of patients with malignant glial tumors. The leukocyte adherence inhibition assay (LAI) was used to measure cell-mediated immunity in 26 patients with malignant glial neoplasms and in 41 control subjects. A significant inhibition of leukocyte adherence was observed in 21 out of 26 (80%) patients with malignant astrocytic gliomas in the presence of a 3M KC1 extract of glioma tissue compared to that of normal brain extract. Among the control group, no significant difference in the percentage of nonadherent leukocytes (NAL) was noted in the presence of either antigen. To study the specificity of the reaction, 3M KC1 extracts of meningioma, pituitary tumor, carcinoma of breast, carcinomas of lung, melanoma, brain, and heart tissues were employed as non-specific antigens. Such studies revealed significantly lower values of NAL. These data indicate that patients with malignant glial neoplasms manifest a cellularimmune response to glioma-associated antigens that can be measured by the tube LAI assay and that LAI assay may render additional useful information in the diagnostic and prognostic evaluation of malignant glial neoplasms."}
{"id": "PMID:233267", "title": "BCNU and steroids in the viral-induced dog brain tumor.", "content": "Schmidt-Ruppin strain of Rous Sarcoma was inoculated intracerebrally into 27 newborn beagle dogs. Fourteen days after viral inoculation, 13 of the dogs were given intravenous BCNU (1 mg/kg). The other 14 were given the same volume of intravenous saline in a randomized, double-blinded fashion. Ninety percent of all dogs developed intracranial tumors. Radionuclide (mercury 197) brain scans were done on each dog at 2-week intervals. Median survival was 113 days in the BCNU group and 115 days in the placebo group (P > .99). Unequivocally positive radionuclide brain scans were detected in 5 dogs treated with BCNU and in 2 of the controls. There were no gross or microscopic differences at autopsy between treated and nontreated animals. BCNU, as given in this animal brain tumor model, did not demonstrate any oncolytic effect. An improvement in sequential brain scans was detected in 2 other dogs in response to Dexamethasone, which was given in a double-blinded, cross-over controlled fashion. Computerized tomography clearly demonstrated the tumor in two cases.", "contents": "BCNU and steroids in the viral-induced dog brain tumor. Schmidt-Ruppin strain of Rous Sarcoma was inoculated intracerebrally into 27 newborn beagle dogs. Fourteen days after viral inoculation, 13 of the dogs were given intravenous BCNU (1 mg/kg). The other 14 were given the same volume of intravenous saline in a randomized, double-blinded fashion. Ninety percent of all dogs developed intracranial tumors. Radionuclide (mercury 197) brain scans were done on each dog at 2-week intervals. Median survival was 113 days in the BCNU group and 115 days in the placebo group (P > .99). Unequivocally positive radionuclide brain scans were detected in 5 dogs treated with BCNU and in 2 of the controls. There were no gross or microscopic differences at autopsy between treated and nontreated animals. BCNU, as given in this animal brain tumor model, did not demonstrate any oncolytic effect. An improvement in sequential brain scans was detected in 2 other dogs in response to Dexamethasone, which was given in a double-blinded, cross-over controlled fashion. Computerized tomography clearly demonstrated the tumor in two cases."}
{"id": "PMID:233273", "title": "Isolation and identification of the Sersenk strain of goat pox virus in Iraq.", "content": "Goat pox virus was isolated during an outbreak of pox infection among goats in the Sersenk district, Iraq. The isolated virus grew on the chorioallantoic membranes of developing chick embryos and in primary lamb testis cell cultures. It was identified morphologically as a pox virus and serologically as a member of the Capripoxvirus group in the family Poxviridae. The isolated virus was designated the \"Sersenk\" strain.", "contents": "Isolation and identification of the Sersenk strain of goat pox virus in Iraq. Goat pox virus was isolated during an outbreak of pox infection among goats in the Sersenk district, Iraq. The isolated virus grew on the chorioallantoic membranes of developing chick embryos and in primary lamb testis cell cultures. It was identified morphologically as a pox virus and serologically as a member of the Capripoxvirus group in the family Poxviridae. The isolated virus was designated the \"Sersenk\" strain."}
{"id": "PMID:233275", "title": "Skin ulceration associated with herpesvirus infection in cats.", "content": "Three cases of skin ulceration in cats are described. Herpesvirus was isolated from the ulcers. Treatment of one case with antibiotics and an antiviral agent was successful. The significance of the viral isolate is discussed.", "contents": "Skin ulceration associated with herpesvirus infection in cats. Three cases of skin ulceration in cats are described. Herpesvirus was isolated from the ulcers. Treatment of one case with antibiotics and an antiviral agent was successful. The significance of the viral isolate is discussed."}
{"id": "PMID:233272", "title": "[A case of \"sensitive deficiency of polyneuropathy\"].", "content": "One case of carential sensitive neuropathy in a patient 47 years old with poor and imbalanced nutrition is reported. The clinical picture is characterized by mucocutaneous lesions, paresthesias like \"burning feet\", serious ataxia. All these symptoms remitted after one year of appropriate therapy. The carential vitaminic aethiology and the nosographic position of the disease are discussed on the basis of the current literature.", "contents": "[A case of \"sensitive deficiency of polyneuropathy\"]. One case of carential sensitive neuropathy in a patient 47 years old with poor and imbalanced nutrition is reported. The clinical picture is characterized by mucocutaneous lesions, paresthesias like \"burning feet\", serious ataxia. All these symptoms remitted after one year of appropriate therapy. The carential vitaminic aethiology and the nosographic position of the disease are discussed on the basis of the current literature."}
{"id": "PMID:233276", "title": "Experimental transmission of bovine papilloma virus (BPV) extracted from morphologically distinct teat and cutaneous lesions and the effects of inoculation of BPV transformed fetal bovine cells.", "content": "Bovine papilloma virus (BPV) was extracted from five cattle each affected with only one of five morphologically distinct lesion types. When inoculated into experimental calves either by scarification or intradermal injection, the BPV extracts produced lesions macroscopically and microscopically similar to those from which individual extracts were made. Fetal bovine cells, transformed in vitro with BPV, failed to produce fibromas, fibropapillomas or papillomas when inoculated into experimental calves. When calves inoculated with virus or BPV transformed cells were challenged with the five original BPV extracts, a differential immunity was demonstrated, while control calves were susceptible to all extracts. Post mortem examination revealed the presence of upper alimentary tract papillomas in three of eight calves forming one group. These results suggest that different strains of BVP, causing morphologically separable lesion types, exist. There may be additional BPV variants causing fibropapillomas of the teat and anogenital regions of cattle. The inoculation of BPV transformed fetal bovine cells conferred a relative immunity to later challenge with some but not all BPV extracts.", "contents": "Experimental transmission of bovine papilloma virus (BPV) extracted from morphologically distinct teat and cutaneous lesions and the effects of inoculation of BPV transformed fetal bovine cells. Bovine papilloma virus (BPV) was extracted from five cattle each affected with only one of five morphologically distinct lesion types. When inoculated into experimental calves either by scarification or intradermal injection, the BPV extracts produced lesions macroscopically and microscopically similar to those from which individual extracts were made. Fetal bovine cells, transformed in vitro with BPV, failed to produce fibromas, fibropapillomas or papillomas when inoculated into experimental calves. When calves inoculated with virus or BPV transformed cells were challenged with the five original BPV extracts, a differential immunity was demonstrated, while control calves were susceptible to all extracts. Post mortem examination revealed the presence of upper alimentary tract papillomas in three of eight calves forming one group. These results suggest that different strains of BVP, causing morphologically separable lesion types, exist. There may be additional BPV variants causing fibropapillomas of the teat and anogenital regions of cattle. The inoculation of BPV transformed fetal bovine cells conferred a relative immunity to later challenge with some but not all BPV extracts."}
{"id": "PMID:233277", "title": "Human adenovirus antibody in sera of normal and tumour-bearing dogs.", "content": "Serum specimens from 42 normal dogs and 42 with untreated malignant tumours were assayed for the presence of antibodies to human adenovirus types 5, 21 and 31 and to infectious canine hepatitis (ICH) virus. Radioimmunoassays using human adenovirus antigens showed that 71 per cent (30/42) of all dogs with tumours, but only 19 per cent (8/42) of all normal dogs, were positive for human adenovirus antibody. Canine sera reactive with antigens of one human adenovirus type in radioimmunoassays were also reactive with antigens of the other two types. Dogs bearing malignant lymphoma or squamous cell carcinoma tumours had higher levels of antibody against adenovirus type 5 antigens. Human adenovirus type 5 was neutralised by sera from four tumour-bearing and two normal dogs, while sera from two normal and five tumour-bearing dogs were positive in immunodiffusion tests with human adenovirus antigens. Levels of ICH antibody in sera of normal adult dogs and adult dogs with tumours were not markedly different when measured by radioimmunoassays. Likewise, sera from these two groups of dogs had similar ranges of ICH neutralising antibody titres. In contrast, levels of ICH antibody detected by the serological assays in sera from non-pet, non-vaccinated pups were either markedly low or absent. Possible explanations for the observed increased levels of human adenovirus antibody in sera of tumour-bearing canine pets are discussed.", "contents": "Human adenovirus antibody in sera of normal and tumour-bearing dogs. Serum specimens from 42 normal dogs and 42 with untreated malignant tumours were assayed for the presence of antibodies to human adenovirus types 5, 21 and 31 and to infectious canine hepatitis (ICH) virus. Radioimmunoassays using human adenovirus antigens showed that 71 per cent (30/42) of all dogs with tumours, but only 19 per cent (8/42) of all normal dogs, were positive for human adenovirus antibody. Canine sera reactive with antigens of one human adenovirus type in radioimmunoassays were also reactive with antigens of the other two types. Dogs bearing malignant lymphoma or squamous cell carcinoma tumours had higher levels of antibody against adenovirus type 5 antigens. Human adenovirus type 5 was neutralised by sera from four tumour-bearing and two normal dogs, while sera from two normal and five tumour-bearing dogs were positive in immunodiffusion tests with human adenovirus antigens. Levels of ICH antibody in sera of normal adult dogs and adult dogs with tumours were not markedly different when measured by radioimmunoassays. Likewise, sera from these two groups of dogs had similar ranges of ICH neutralising antibody titres. In contrast, levels of ICH antibody detected by the serological assays in sera from non-pet, non-vaccinated pups were either markedly low or absent. Possible explanations for the observed increased levels of human adenovirus antibody in sera of tumour-bearing canine pets are discussed."}
{"id": "PMID:233278", "title": "The demonstration of maedi/visna virus in sheep in Great Britain.", "content": "A virus indistinguishable from that causing maedi/visna has been isolated from a sheep flock in Great Britain. The virus was identified in cell cultures using immunofluorescent and electron microscopical techniques. The complement fixation test and the agar gel immunodiffusion test were used to assess the proportion of serological reactors within the flock. There has been no evidence of clinical disease in the flock into which foreign imports were introduced in the years prior to 1976.", "contents": "The demonstration of maedi/visna virus in sheep in Great Britain. A virus indistinguishable from that causing maedi/visna has been isolated from a sheep flock in Great Britain. The virus was identified in cell cultures using immunofluorescent and electron microscopical techniques. The complement fixation test and the agar gel immunodiffusion test were used to assess the proportion of serological reactors within the flock. There has been no evidence of clinical disease in the flock into which foreign imports were introduced in the years prior to 1976."}
{"id": "PMID:233283", "title": "Histological and histoenzymological studies of medulla oblongata of Taphozous melanopogon Temminck (a Microchiroptera).", "content": "The paper deals with the histological and histoenzymological studies of the medulla oblongata of Taphozous melanopogon Temminck (a microchiropteran bat). Three phosphatases, namely acid phosphatase (ACP), thiamine pyrophosphatase (TTP) and glucose-6-phosphatase (G-6-P) were studied. All the enzymes were seen in all the neurons. The large neurons of the different nuclei are more strongly positive for ACP than the small neurons. Further, the areas which contain dense populations of neurons are more strongly stained than the area containing scattered neurons. TPP and G-6-P distributions are almost parallel to that of ACP. The functions of these enzymes in synthesis and secretory processes were discussed.", "contents": "Histological and histoenzymological studies of medulla oblongata of Taphozous melanopogon Temminck (a Microchiroptera). The paper deals with the histological and histoenzymological studies of the medulla oblongata of Taphozous melanopogon Temminck (a microchiropteran bat). Three phosphatases, namely acid phosphatase (ACP), thiamine pyrophosphatase (TTP) and glucose-6-phosphatase (G-6-P) were studied. All the enzymes were seen in all the neurons. The large neurons of the different nuclei are more strongly positive for ACP than the small neurons. Further, the areas which contain dense populations of neurons are more strongly stained than the area containing scattered neurons. TPP and G-6-P distributions are almost parallel to that of ACP. The functions of these enzymes in synthesis and secretory processes were discussed."}
{"id": "PMID:233284", "title": "Gastric carcinoma in dogs produced by the combined use of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) and gastrin--with special reference to development of scirrhous carcinoma.", "content": "Eight beagle dogs of four-month-old received both oral administration of N-Ethyl-N'-Nitro-N-Nitrosoguanidine (ENNG) and subcutaneous injection of gastrin, and one of them was found to have an annularly infiltrating advanced carcinoma with marked fibrous thickening of the antral wall resulting in stenosis of the antrum (carcinoma scirrhosum) which resembled \"Linitis plastica\" (Borrmann's type IV carcinoma) in human stomach.", "contents": "Gastric carcinoma in dogs produced by the combined use of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) and gastrin--with special reference to development of scirrhous carcinoma. Eight beagle dogs of four-month-old received both oral administration of N-Ethyl-N'-Nitro-N-Nitrosoguanidine (ENNG) and subcutaneous injection of gastrin, and one of them was found to have an annularly infiltrating advanced carcinoma with marked fibrous thickening of the antral wall resulting in stenosis of the antrum (carcinoma scirrhosum) which resembled \"Linitis plastica\" (Borrmann's type IV carcinoma) in human stomach."}
{"id": "PMID:233285", "title": "Adult T-cell leukemia with generalized cytomegalic inclusion disease and pneumocystis carinii pneumonia.", "content": "An autopsy case of adult T-cell leukemia with generalized cytomegalic inclusion disease and pneumocystis carinii pneumonia is reported. Tumor cells had T-cell characteristics (E-rosette) and cerebriform nucleus similar to S\u00e8zary cells. Generalized lymphadenopathy, hepatosplenomegaly and an ectopic pancreas in the ileum were found at the time of autopsy. Histologically, leukemic infiltration was observed in almost every organ, and perivascular infiltration, vascular invasion were conspicuous findings. Cytomegalic inclusion bodies were observed in most organs (lungs, salivary glands, pancreas, liver, ectopic pancreas, sweat gland, stomach, thyroid gland, pituitary body, etc.). An acute hepatitis, probably caused by cytomegalovirus, was also noted. Presumed correlation of adult T-cell leukemia, cutaneous T-cell lymphoma and T-cell lymphoma was discussed.", "contents": "Adult T-cell leukemia with generalized cytomegalic inclusion disease and pneumocystis carinii pneumonia. An autopsy case of adult T-cell leukemia with generalized cytomegalic inclusion disease and pneumocystis carinii pneumonia is reported. Tumor cells had T-cell characteristics (E-rosette) and cerebriform nucleus similar to S\u00e8zary cells. Generalized lymphadenopathy, hepatosplenomegaly and an ectopic pancreas in the ileum were found at the time of autopsy. Histologically, leukemic infiltration was observed in almost every organ, and perivascular infiltration, vascular invasion were conspicuous findings. Cytomegalic inclusion bodies were observed in most organs (lungs, salivary glands, pancreas, liver, ectopic pancreas, sweat gland, stomach, thyroid gland, pituitary body, etc.). An acute hepatitis, probably caused by cytomegalovirus, was also noted. Presumed correlation of adult T-cell leukemia, cutaneous T-cell lymphoma and T-cell lymphoma was discussed."}
{"id": "PMID:233286", "title": "Vascular leiomyoblastoma of the stomach -- Observations supporting its origin from Zimmermann's pericyte.", "content": "Gastric leiomyoblastoma with small mesenteric metastasis in a 44-year-old man has been studied by light and electron microscopy. Histologically, the tumor, having \"epithelioid\" tumor cells mixed with spindle leiomyomatous cells, was rich in blood vessels and focally simulated hemangiopericytoma. Electron microscopy revealed the tumor cells in variable stages of differentiation from poorly differentiated polygonal cells to smooth muscular cells. The intermediate cells had numerous cytoplasmic processes which interlocked each other. In addition, an intimate association was noted between the tumor cell processes and the small vessels including capillaries. With the recent characterization of the pericyte as a pluripotent mesenchymal cell that may serve as a precursor to the vascular smooth muscle cell, the present observations support the view that some leiomyoblastomas originate from the pericyte of Zimmermann. Leiomyoblastoma may be placed between hemangiopericytoma and glomus tumor in the spectrum of pericytic tumors.", "contents": "Vascular leiomyoblastoma of the stomach -- Observations supporting its origin from Zimmermann's pericyte. Gastric leiomyoblastoma with small mesenteric metastasis in a 44-year-old man has been studied by light and electron microscopy. Histologically, the tumor, having \"epithelioid\" tumor cells mixed with spindle leiomyomatous cells, was rich in blood vessels and focally simulated hemangiopericytoma. Electron microscopy revealed the tumor cells in variable stages of differentiation from poorly differentiated polygonal cells to smooth muscular cells. The intermediate cells had numerous cytoplasmic processes which interlocked each other. In addition, an intimate association was noted between the tumor cell processes and the small vessels including capillaries. With the recent characterization of the pericyte as a pluripotent mesenchymal cell that may serve as a precursor to the vascular smooth muscle cell, the present observations support the view that some leiomyoblastomas originate from the pericyte of Zimmermann. Leiomyoblastoma may be placed between hemangiopericytoma and glomus tumor in the spectrum of pericytic tumors."}
{"id": "PMID:233287", "title": "Primitive neuroectodermal tumor (neuroepithelioma) of spinal nerve root -- Report of an adult case and establishment of a cell line.", "content": "A case of primitive neuroectodermal tumor arising in the cervical nerve root of a 28-year-old man is presented. Histologically, the tumor was characterised by proliferation of primitive neuroectodermal cells and formation of numerous Homer-Wright type rosettes. A cell line (Nagai line) was established from the tumor. Electron microscopic examination of Nagai cells revealed numerous microrosette formation with microvilli-like cytoplasmic processes projecting into the central lumina. Neurosecretory granules appeared in the cytoplasmic processes when Nagai cells were treated with dibutyryl cyclic AMP. Primitive satellite cells which completely surrounded other tumor cells with their tongue-like slender cytoplasmic processes were also found. Histogenesis of this unique tumor was discussed comparing with the neuroblastoma of sympathetic nervous system, medulloblastoma of the central nervous system, and with the tumors induced by Adenovirus type 12 in animals. It was concluded that the tumor was neuroepithelioma derived from a primitive stem cell of neural crest origin which possesses the bipotency to differentiate toward either neuroblastic or neurilemmal line.", "contents": "Primitive neuroectodermal tumor (neuroepithelioma) of spinal nerve root -- Report of an adult case and establishment of a cell line. A case of primitive neuroectodermal tumor arising in the cervical nerve root of a 28-year-old man is presented. Histologically, the tumor was characterised by proliferation of primitive neuroectodermal cells and formation of numerous Homer-Wright type rosettes. A cell line (Nagai line) was established from the tumor. Electron microscopic examination of Nagai cells revealed numerous microrosette formation with microvilli-like cytoplasmic processes projecting into the central lumina. Neurosecretory granules appeared in the cytoplasmic processes when Nagai cells were treated with dibutyryl cyclic AMP. Primitive satellite cells which completely surrounded other tumor cells with their tongue-like slender cytoplasmic processes were also found. Histogenesis of this unique tumor was discussed comparing with the neuroblastoma of sympathetic nervous system, medulloblastoma of the central nervous system, and with the tumors induced by Adenovirus type 12 in animals. It was concluded that the tumor was neuroepithelioma derived from a primitive stem cell of neural crest origin which possesses the bipotency to differentiate toward either neuroblastic or neurilemmal line."}
{"id": "PMID:233288", "title": "Gaucher-like cells in juvenile GM1-gangliosidosis and in beta-thalassemia -- A histochemical and ultrastructural observation.", "content": "Peculiar storage cells appearing in bone marrow aspirates from a patient with juvenile GM1-gangliosidosis and from one with beta-thalassemia were examined light microscopically, histochemically and electron microscopically. Light microscopically, most of the storage cells closely resembled Gaucher cells pathognomonic for Gaucher's disease. The cytoplasm of the Gaucher-like cells contained numerous variable-shaped membrane-bound inclusions mostly arranged in a mosaic pattern and filled with fibrillar materials. Intermingled tubular structures were usually narrow as compared to those of the Gaucher cells. These ultrastructural differences of the stored materials between the Gaucher-like cells and Gaucher cells were more clearly substantiated by the high resolution electron microscopy with negative staining technique. Enzyme cytochemically, acid phosphatase activity was proved in or around the storage inclusions, suggesting their lysosomal origin. Histochemically, it might be suggested that the stored materials of the Gaucher-like cells in juvenile GMI-gangliosidosis were non-sulfated acid mucopolysaccharides and glycopeptides, whereas glycoproteins were the major component of the storage cells in beta-thalassemia. Possible mechanisms of storage in the Gaucher-like cells were discussed in both disorders.", "contents": "Gaucher-like cells in juvenile GM1-gangliosidosis and in beta-thalassemia -- A histochemical and ultrastructural observation. Peculiar storage cells appearing in bone marrow aspirates from a patient with juvenile GM1-gangliosidosis and from one with beta-thalassemia were examined light microscopically, histochemically and electron microscopically. Light microscopically, most of the storage cells closely resembled Gaucher cells pathognomonic for Gaucher's disease. The cytoplasm of the Gaucher-like cells contained numerous variable-shaped membrane-bound inclusions mostly arranged in a mosaic pattern and filled with fibrillar materials. Intermingled tubular structures were usually narrow as compared to those of the Gaucher cells. These ultrastructural differences of the stored materials between the Gaucher-like cells and Gaucher cells were more clearly substantiated by the high resolution electron microscopy with negative staining technique. Enzyme cytochemically, acid phosphatase activity was proved in or around the storage inclusions, suggesting their lysosomal origin. Histochemically, it might be suggested that the stored materials of the Gaucher-like cells in juvenile GMI-gangliosidosis were non-sulfated acid mucopolysaccharides and glycopeptides, whereas glycoproteins were the major component of the storage cells in beta-thalassemia. Possible mechanisms of storage in the Gaucher-like cells were discussed in both disorders."}
{"id": "PMID:233289", "title": "The sensitivity of phage DNA and plasmid DNA for a restriction enzyme for Staphylococcus aureus.", "content": "In Staphylococcus aureus transduction of different tetracycline and chloramphenicol plasmids with a group I/III modification was possible to group I and III strains. Group II strains, containing a restriction endonuclease, had a restriction both for the phage and the plasmids: two restriction-deficient group II strains were good acceptors for these plasmids.", "contents": "The sensitivity of phage DNA and plasmid DNA for a restriction enzyme for Staphylococcus aureus. In Staphylococcus aureus transduction of different tetracycline and chloramphenicol plasmids with a group I/III modification was possible to group I and III strains. Group II strains, containing a restriction endonuclease, had a restriction both for the phage and the plasmids: two restriction-deficient group II strains were good acceptors for these plasmids."}
{"id": "PMID:233290", "title": "Chemical and electron microscopic studies of factors associated with the release of penicillinase from Staphylococcus aureus.", "content": "The effect of various factors such as sodium chloride, sodium citrate, pH, linase by Staphylococcus aureus ATCC 14458 was investigated. Penicillinase was measured at selected time intervals from supernates of cultures grown in Antibiotic Medium 3 broth containing various concentrations of salts or buffers or from supernates of cultures treated with lysostaphin and subsequently disrupted by French press treatment. Incubation of cells with media containing either sodium chloride (5, 10, and 15%), sodium citrate (5 and 10%), or organic buffers (Tris-HCl, 2.5, 5.0, and 7.5%; BES, 10 and 20%) resulted in a significant stimulation of the release of penicillinase when compared to control cells. It was also observed that pH 7.0-7.5 was optimal for penicillinase activity and release. From studies of enzymatic and mechanical disruption of cells, it was observed that an increase in ionic strength of the suspending medium to certain optimal levels appeared to stimulate the conversion of penicillinase to an extracellular form. Electron microscopic studies revealed that a large number of mesosomal vesicles seemed to be present in cells incubated for 4 hours in media containing various concentrations of sodium chloride. It is proposed that either appearance of vesicles or convolution of cell membrane, which may be caused by further synthesis of new membrane, is involved in stimulation of the synthesis and release of membrane-bound penicillinase.", "contents": "Chemical and electron microscopic studies of factors associated with the release of penicillinase from Staphylococcus aureus. The effect of various factors such as sodium chloride, sodium citrate, pH, linase by Staphylococcus aureus ATCC 14458 was investigated. Penicillinase was measured at selected time intervals from supernates of cultures grown in Antibiotic Medium 3 broth containing various concentrations of salts or buffers or from supernates of cultures treated with lysostaphin and subsequently disrupted by French press treatment. Incubation of cells with media containing either sodium chloride (5, 10, and 15%), sodium citrate (5 and 10%), or organic buffers (Tris-HCl, 2.5, 5.0, and 7.5%; BES, 10 and 20%) resulted in a significant stimulation of the release of penicillinase when compared to control cells. It was also observed that pH 7.0-7.5 was optimal for penicillinase activity and release. From studies of enzymatic and mechanical disruption of cells, it was observed that an increase in ionic strength of the suspending medium to certain optimal levels appeared to stimulate the conversion of penicillinase to an extracellular form. Electron microscopic studies revealed that a large number of mesosomal vesicles seemed to be present in cells incubated for 4 hours in media containing various concentrations of sodium chloride. It is proposed that either appearance of vesicles or convolution of cell membrane, which may be caused by further synthesis of new membrane, is involved in stimulation of the synthesis and release of membrane-bound penicillinase."}
{"id": "PMID:233292", "title": "Regulation of collagen synthesis and maturation by 3,4-dehydroproline.", "content": "Proline analogs are readily incorporated into collagen and noncollagen proteins. Since the imino acid content of collagen is greater than other proteins, it is suggested that the incorporation of a proline analog into cellular protein would have a maximal effect on collagen metabolism. Using a partially purified amino acyl tRNA synthetase preparation, various proline analogs were tested for their ability to inhibit Pro-tRNA synthesis. Amongst those tested, dehydroproline was the preferred inhibitor. Dehydroproline was also a substrate for amino acyl tRNA synthetase. When dehydroproline was added in vitro to membrane bound polysomes, the synthesis of collagenous proteins was preferentially inhibited. The addition of dehydroproline to mammalian cell cultures caused a marked reduction in prolyl hydroxylase activity. Under these conditions growth of cells, activities of lysyl; hydroxylase or lactic dehydrogenase were not affected. Reduction of prolyl hydroxylase activity by dehydroproline required protein synthesis. Removal of dehydroproline from the growth medium resulted in an increase in prolylhydroxylase activity. Hepatic fibrosis can be induced in rats by chronic administration of carbon tetrachloride. Under these conditions, the collagen content and prolyl hydroxylase activity of the liver is enhanced. Treatment of these fibrotic animals with dehydroproline results in a reduction of prolyl hydroxylase activity of the liver. A mechanism by which dehydroproline reduces prolyl hydroxylase activity will be discussed. Since prolyl hydroxylase plays a key role in the maturation and deposition of collagen, specific inhibitors of this enzyme are potentially useful in controlling collagen deposition in various pathological conditions.", "contents": "Regulation of collagen synthesis and maturation by 3,4-dehydroproline. Proline analogs are readily incorporated into collagen and noncollagen proteins. Since the imino acid content of collagen is greater than other proteins, it is suggested that the incorporation of a proline analog into cellular protein would have a maximal effect on collagen metabolism. Using a partially purified amino acyl tRNA synthetase preparation, various proline analogs were tested for their ability to inhibit Pro-tRNA synthesis. Amongst those tested, dehydroproline was the preferred inhibitor. Dehydroproline was also a substrate for amino acyl tRNA synthetase. When dehydroproline was added in vitro to membrane bound polysomes, the synthesis of collagenous proteins was preferentially inhibited. The addition of dehydroproline to mammalian cell cultures caused a marked reduction in prolyl hydroxylase activity. Under these conditions growth of cells, activities of lysyl; hydroxylase or lactic dehydrogenase were not affected. Reduction of prolyl hydroxylase activity by dehydroproline required protein synthesis. Removal of dehydroproline from the growth medium resulted in an increase in prolylhydroxylase activity. Hepatic fibrosis can be induced in rats by chronic administration of carbon tetrachloride. Under these conditions, the collagen content and prolyl hydroxylase activity of the liver is enhanced. Treatment of these fibrotic animals with dehydroproline results in a reduction of prolyl hydroxylase activity of the liver. A mechanism by which dehydroproline reduces prolyl hydroxylase activity will be discussed. Since prolyl hydroxylase plays a key role in the maturation and deposition of collagen, specific inhibitors of this enzyme are potentially useful in controlling collagen deposition in various pathological conditions."}
{"id": "PMID:233293", "title": "Induction of germination in Blastocladiella emersonii by cyclic AMP and inhibitors of cyclic AMP phosphodiesterase.", "content": "Since K+-induced germination of Blastocladiella emersonii is accompanied by a rapid decrease of a specific cyclic AMP phosphodiesterase (cAMP PDE) activity and a transient cyclic AMP accumulation, the effects of this compound as well as of some inhibitors of cAMP PDE on the induction of germination were tested. Adenine and caffeine, competitive inhibitors of zoospore cAMP PDE, were able to elicit germination in substitution for K+. Cyclic AMP is a poor inducer, but a synergistic effect was evident when non-effective concentrations of K+ and cyclic AMP were added together to the medium. At the same concentration, cyclic GMP had no effect as compared with cyclic AMP. Lanthanum, a specific antagonist of calcium in several biological systems, completely blocked the germination induced by potassium.", "contents": "Induction of germination in Blastocladiella emersonii by cyclic AMP and inhibitors of cyclic AMP phosphodiesterase. Since K+-induced germination of Blastocladiella emersonii is accompanied by a rapid decrease of a specific cyclic AMP phosphodiesterase (cAMP PDE) activity and a transient cyclic AMP accumulation, the effects of this compound as well as of some inhibitors of cAMP PDE on the induction of germination were tested. Adenine and caffeine, competitive inhibitors of zoospore cAMP PDE, were able to elicit germination in substitution for K+. Cyclic AMP is a poor inducer, but a synergistic effect was evident when non-effective concentrations of K+ and cyclic AMP were added together to the medium. At the same concentration, cyclic GMP had no effect as compared with cyclic AMP. Lanthanum, a specific antagonist of calcium in several biological systems, completely blocked the germination induced by potassium."}
{"id": "PMID:233294", "title": "Role of hemolytic factors of Sendai virus on human erythrocyte membrane fluidity.", "content": "In order to establish whether the hemolytic activity of Sendai virus might be related to changes of the membrane fluidity of sensitive cells, membrane fluidity variations have been recorded in human erythrocytes ghosts in the presence of Sendai and PR 8 viral particles. A decrease of membrane fluidity is elicited by Sendai and Pr 8 virions and by non hemolytic Sendai virus after trypsinization; the effect on membrane fluidity of sendai virus is strongly reduced after pyridine treatment which abolishes hemolytic action.", "contents": "Role of hemolytic factors of Sendai virus on human erythrocyte membrane fluidity. In order to establish whether the hemolytic activity of Sendai virus might be related to changes of the membrane fluidity of sensitive cells, membrane fluidity variations have been recorded in human erythrocytes ghosts in the presence of Sendai and PR 8 viral particles. A decrease of membrane fluidity is elicited by Sendai and Pr 8 virions and by non hemolytic Sendai virus after trypsinization; the effect on membrane fluidity of sendai virus is strongly reduced after pyridine treatment which abolishes hemolytic action."}
{"id": "PMID:233295", "title": "Identification of a glycoprotein inhibitor of human serum, active towards the hemagglutinating activity of Sendai virus.", "content": "Non-antibody hemagglutination-inhibiting activity of human serum is due, at least partially, to a glycoprotein inhibitor. This inhibitor was obtained from the whole serum or the fraction VI (Cohn) by means of methods of purification generally used for the preparation of the orosomucoid and was identified more precisely with an acid alpha 1-glycoprotein.", "contents": "Identification of a glycoprotein inhibitor of human serum, active towards the hemagglutinating activity of Sendai virus. Non-antibody hemagglutination-inhibiting activity of human serum is due, at least partially, to a glycoprotein inhibitor. This inhibitor was obtained from the whole serum or the fraction VI (Cohn) by means of methods of purification generally used for the preparation of the orosomucoid and was identified more precisely with an acid alpha 1-glycoprotein."}
{"id": "PMID:233296", "title": "Decline in incidence of hepatitis A infection in Milan. A serologic study.", "content": "The availability of serum samples collected in 1958 and in 1977 from healthy individuals of Milan, has provided an opportunity to compare the prevalence of anti-HAV and anti-HBs in the same area at a distance of about 20 years. The results obtained show a general drop of anti-HAV rate from 1958 to 1977. Difference in antibody prevalence was found to be significantly remarkable (35.7% versus 3.6%, P < 0.05 and 78.6% versus 26.9%, P < 0.01) in the youngest age groups examined (1-5 and 6-15 years old). Moreover the plateau of antibody acquisition was reached over 30 years of age in people selected in 1958 and over 50 years in 1977. No substantial difference was found in anti-HBs prevalence in sera collected in 1958 and in 1977 (29.2% versus 29.3%). The finding of a decline in hepatitis A infection may reflect the improvements in public health and hygienic conditions which occurred in our city in the last decades, whereas with regard to hepatitis B, the maintenance of the same incidence of infection may be due to different contributory factors.", "contents": "Decline in incidence of hepatitis A infection in Milan. A serologic study. The availability of serum samples collected in 1958 and in 1977 from healthy individuals of Milan, has provided an opportunity to compare the prevalence of anti-HAV and anti-HBs in the same area at a distance of about 20 years. The results obtained show a general drop of anti-HAV rate from 1958 to 1977. Difference in antibody prevalence was found to be significantly remarkable (35.7% versus 3.6%, P < 0.05 and 78.6% versus 26.9%, P < 0.01) in the youngest age groups examined (1-5 and 6-15 years old). Moreover the plateau of antibody acquisition was reached over 30 years of age in people selected in 1958 and over 50 years in 1977. No substantial difference was found in anti-HBs prevalence in sera collected in 1958 and in 1977 (29.2% versus 29.3%). The finding of a decline in hepatitis A infection may reflect the improvements in public health and hygienic conditions which occurred in our city in the last decades, whereas with regard to hepatitis B, the maintenance of the same incidence of infection may be due to different contributory factors."}
{"id": "PMID:233297", "title": "[Observations on the diffusion of hepatitis A and B virus during an epidemic in a Sicilian town with a high rate of infection].", "content": "Epidemiological investigations were carried out during a viral hepatitis outbreak occurring in a Sicilian town of 30,000 inhabitants with poor sanitary standards, with the aim to study the mode of spread of HAV and HBV in conditions of high incidence of infections. HBsAg, anti HBs, anti HAV (RIA), HBeAg, anti HBe and anti HBc were investigated in serum samples from patients, their family contacts and from healthy individuals of different age groups. Morbidity was inferred from case notifications; search of unreported cases among school children, through the study of absenteeism, did not reveal further cases. In all 148 cases, occurred from August 1976 through July 1977 with a peak in January, 44% were under 5 and 93% under 10 years of age. All but 8 of 59 cases in which laboratory data were available were due to HAV. Anti HAV antibodies were highly prevalent in serum samples obtained in February through April 1977: 62% were positive in the 1 to 3 years age group, and more than 90% among school children. Prevalence of HBsAg was age and sex dependent, ranging from 4% to 15%; anti HBs was present in 8% of the children 1-10 years and in 30% or more in age groups 30-41 and over. It is suggested that direct contact between very young children was the main mode of spread of HAV, and inapparent cases the main source of infection, although ambient diffusion through water contamination could not ruled out. HBV was probably propagated mostly by intrafamilial spread with little overt pathology.", "contents": "[Observations on the diffusion of hepatitis A and B virus during an epidemic in a Sicilian town with a high rate of infection]. Epidemiological investigations were carried out during a viral hepatitis outbreak occurring in a Sicilian town of 30,000 inhabitants with poor sanitary standards, with the aim to study the mode of spread of HAV and HBV in conditions of high incidence of infections. HBsAg, anti HBs, anti HAV (RIA), HBeAg, anti HBe and anti HBc were investigated in serum samples from patients, their family contacts and from healthy individuals of different age groups. Morbidity was inferred from case notifications; search of unreported cases among school children, through the study of absenteeism, did not reveal further cases. In all 148 cases, occurred from August 1976 through July 1977 with a peak in January, 44% were under 5 and 93% under 10 years of age. All but 8 of 59 cases in which laboratory data were available were due to HAV. Anti HAV antibodies were highly prevalent in serum samples obtained in February through April 1977: 62% were positive in the 1 to 3 years age group, and more than 90% among school children. Prevalence of HBsAg was age and sex dependent, ranging from 4% to 15%; anti HBs was present in 8% of the children 1-10 years and in 30% or more in age groups 30-41 and over. It is suggested that direct contact between very young children was the main mode of spread of HAV, and inapparent cases the main source of infection, although ambient diffusion through water contamination could not ruled out. HBV was probably propagated mostly by intrafamilial spread with little overt pathology."}
{"id": "PMID:233300", "title": "Galactose-1-phosphate uridylyltransferase activity in chronic lymphocytic leukemia.", "content": "Galactose-1-phosphate uridylytransferase (E.C.2.7.12) activity was measured in both lymphoid and erythroid cells from patients with chronic lymphocytic leukemia (CLL). Decreased enzyme activity was found in both cell types using two assay methods. The results suggest the presence of an inhibitor of the enzyme in CLL patients. A correlation between decreased uridyl transferase activity and glycogen accumulation in CLL is postulated.", "contents": "Galactose-1-phosphate uridylyltransferase activity in chronic lymphocytic leukemia. Galactose-1-phosphate uridylytransferase (E.C.2.7.12) activity was measured in both lymphoid and erythroid cells from patients with chronic lymphocytic leukemia (CLL). Decreased enzyme activity was found in both cell types using two assay methods. The results suggest the presence of an inhibitor of the enzyme in CLL patients. A correlation between decreased uridyl transferase activity and glycogen accumulation in CLL is postulated."}
{"id": "PMID:233301", "title": "Serum lipoproteins in rats bearing Morris hepatomas of different degrees of differentiation.", "content": "Serum lipoproteins were measured by ultracentrifugal means in rats bearing hepatomas of different degrees of malignancy (Morris hepatomas 16, 5123TC and 7777) to determine the effect of these hepatomas on serum lipoprotein levels. Serum lipoprotein patterns were altered, especially in rats bearing hepatomas 16 and 7777, which had elevated high-density lipoproteins. (They were not elevated in serum of rats bearing hepatoma 5123TC). This increase in high-density lipoproteins seems to be specific for chemically induced hepatomas since HDL2 is usually decreased in humans and animals with types of cancer not involving the liver. It appears that hepatomas can synthesize lipoproteins, and the serum levels of the host rats are altered depending on the hepatoma. Different biochemistries appear to be associated with each hepatoma. Cholesterol and fatty acid levels of unfractionated serum and of isolated lipoproteins also indicate abnormal lipid/lipoprotein metabolism associated with these hepatomas.", "contents": "Serum lipoproteins in rats bearing Morris hepatomas of different degrees of differentiation. Serum lipoproteins were measured by ultracentrifugal means in rats bearing hepatomas of different degrees of malignancy (Morris hepatomas 16, 5123TC and 7777) to determine the effect of these hepatomas on serum lipoprotein levels. Serum lipoprotein patterns were altered, especially in rats bearing hepatomas 16 and 7777, which had elevated high-density lipoproteins. (They were not elevated in serum of rats bearing hepatoma 5123TC). This increase in high-density lipoproteins seems to be specific for chemically induced hepatomas since HDL2 is usually decreased in humans and animals with types of cancer not involving the liver. It appears that hepatomas can synthesize lipoproteins, and the serum levels of the host rats are altered depending on the hepatoma. Different biochemistries appear to be associated with each hepatoma. Cholesterol and fatty acid levels of unfractionated serum and of isolated lipoproteins also indicate abnormal lipid/lipoprotein metabolism associated with these hepatomas."}
{"id": "PMID:233302", "title": "Influence of charge on the inactivation of membrane bound (Na+ + K+)-ATPase of Yoshida sarcoma cells by inhibitor proteins from cobra venom.", "content": "Inactivation of (Na+ + K+)-ATPase of Yoshida sarcoma cells and beef brain microsomes by phospholipase A2 and a cytotoxin P6 from snake venom has been examined in relation to their activity to degrade phospholipids. Cytotoxin P6 which was most basic and devoid of phospholipase activity was most effective in inhibiting the (Na+ + K+)-ATPase of Yoshida sarcoma cells. Phospholipase A2 from Naja naja which was most active in degrading phospholipids was least effective in inhibiting (Na+ + K+)-ATPase in Yoshida sarcoma cells or in beef brain microsomes. Addition of trace amounts of cytotoxin P6 to the phospholipase considerably enhanced the inactivation of (Na+ + K+)-ATPase. The evidence suggests that the charge of the inhibitor protein and its specific structure play an important role in the inactivation of (Na+ + K+)-ATPase.", "contents": "Influence of charge on the inactivation of membrane bound (Na+ + K+)-ATPase of Yoshida sarcoma cells by inhibitor proteins from cobra venom. Inactivation of (Na+ + K+)-ATPase of Yoshida sarcoma cells and beef brain microsomes by phospholipase A2 and a cytotoxin P6 from snake venom has been examined in relation to their activity to degrade phospholipids. Cytotoxin P6 which was most basic and devoid of phospholipase activity was most effective in inhibiting the (Na+ + K+)-ATPase of Yoshida sarcoma cells. Phospholipase A2 from Naja naja which was most active in degrading phospholipids was least effective in inhibiting (Na+ + K+)-ATPase in Yoshida sarcoma cells or in beef brain microsomes. Addition of trace amounts of cytotoxin P6 to the phospholipase considerably enhanced the inactivation of (Na+ + K+)-ATPase. The evidence suggests that the charge of the inhibitor protein and its specific structure play an important role in the inactivation of (Na+ + K+)-ATPase."}
{"id": "PMID:233298", "title": "Influence of metaphos on the structuro-functional organization of mitochondrial membranes.", "content": "It has been established by methods of spectrophotometry and spin probe that the organophosphorus pesticide metaphos, widely used in practice, is an inhibitor of NADH2 oxidase of the respiratory chain of the mitochondria and exerts an influence on the structural organization of the mitochondrial membrane. An effect of metaphos on the nature of the distribution and kinetics of NADH2-induced death of monoradical spin probes of various chemical structures was detected in a suspension of submitochondrial particles obtained from beef heart.", "contents": "Influence of metaphos on the structuro-functional organization of mitochondrial membranes. It has been established by methods of spectrophotometry and spin probe that the organophosphorus pesticide metaphos, widely used in practice, is an inhibitor of NADH2 oxidase of the respiratory chain of the mitochondria and exerts an influence on the structural organization of the mitochondrial membrane. An effect of metaphos on the nature of the distribution and kinetics of NADH2-induced death of monoradical spin probes of various chemical structures was detected in a suspension of submitochondrial particles obtained from beef heart."}
{"id": "PMID:233303", "title": "Phosphonoacetic acid: inhibition of transformation of human cord blood lymphocytes by Epstein-Barr virus.", "content": "Phosphonoacetic acid disodium salt (PAA) inhibited the transformation of human cord blood lymphocytes by Epstein-Barr virus (EBV) at concentrations of 50-100 microgram/ml. At these concentrations, PAA had no effect on the multiplication of EBV transformed human lymphoblastoid cells or on the survival of human cord blood lymphocytes. The transformation of human cord blood lymphocytes by the B95-8 strain of EBV was measured by 3H-thymidine uptake, 5 days or more after infection. The degree of inhibition of transformation was correlated with the relation between the input of EBV and the concentration of PAA in the experiment. PAA inhibited the transformation even when added 24 h after EBV infection, but had no effect when added 48 h after EBV infection. The inhibitory effect of PAA could be overcome by its removal and normal 3H-thymidine uptake was restored even after 6 days of inhibition. The specificity of the inhibitory effect on EBV induced transformation of human cord blood lymphocytes is discussed.", "contents": "Phosphonoacetic acid: inhibition of transformation of human cord blood lymphocytes by Epstein-Barr virus. Phosphonoacetic acid disodium salt (PAA) inhibited the transformation of human cord blood lymphocytes by Epstein-Barr virus (EBV) at concentrations of 50-100 microgram/ml. At these concentrations, PAA had no effect on the multiplication of EBV transformed human lymphoblastoid cells or on the survival of human cord blood lymphocytes. The transformation of human cord blood lymphocytes by the B95-8 strain of EBV was measured by 3H-thymidine uptake, 5 days or more after infection. The degree of inhibition of transformation was correlated with the relation between the input of EBV and the concentration of PAA in the experiment. PAA inhibited the transformation even when added 24 h after EBV infection, but had no effect when added 48 h after EBV infection. The inhibitory effect of PAA could be overcome by its removal and normal 3H-thymidine uptake was restored even after 6 days of inhibition. The specificity of the inhibitory effect on EBV induced transformation of human cord blood lymphocytes is discussed."}
{"id": "PMID:233304", "title": "Distribution of 2,2,6,6-tetramethyl-4-oxopiperidine-1-oxyl free radical in normal and neoplastic animal tissues.", "content": "The free radical 2,2,6,6-tetramethyl-4-oxopiperidine-1-oxyl (TMPO) was injected i.p. in doses of 100 mg/kg bw into Syrian hamsters: untreated, partially hepatectomized and grafted with transplantable tumours as well as into mice with B16 melanotic melanoma or with an adenocarcinoma. One hour after application of the compound its content was determined spectrometrically in livers, kidneys, lungs and all tumours. The characteristic triplet signal of TMPO was registered in the hamster and mouse melanotic melanomas but not in all other animal tissues and tumours. This may be the result of an enzyme defect in the melanotic melanoma cells or of a retention of TMPO by melanin. It was also found that TMPO is metabolized predominantly in the livers of the animals.", "contents": "Distribution of 2,2,6,6-tetramethyl-4-oxopiperidine-1-oxyl free radical in normal and neoplastic animal tissues. The free radical 2,2,6,6-tetramethyl-4-oxopiperidine-1-oxyl (TMPO) was injected i.p. in doses of 100 mg/kg bw into Syrian hamsters: untreated, partially hepatectomized and grafted with transplantable tumours as well as into mice with B16 melanotic melanoma or with an adenocarcinoma. One hour after application of the compound its content was determined spectrometrically in livers, kidneys, lungs and all tumours. The characteristic triplet signal of TMPO was registered in the hamster and mouse melanotic melanomas but not in all other animal tissues and tumours. This may be the result of an enzyme defect in the melanotic melanoma cells or of a retention of TMPO by melanin. It was also found that TMPO is metabolized predominantly in the livers of the animals."}
{"id": "PMID:233310", "title": "Fast excitatory postsynaptic currents in voltage-clamped mammalian sympathetic ganglion neurones.", "content": "Fast excitatory postsynaptic currents (EPSCs) were recorded in voltage-clamped neurones of isolated superior cervical ganglion of the rabbit. The rise time, decay time and whole duration of EPSC, as well as miniature EPSC, were shorter than those of corresponding postsynaptic potentials. Characteristic impedance for EPSC was 5.5 +/- 1.1 M omega, and was a few times lower than for current evoked by iontophoretic application of ACh. The rise time of EPSC was 2.0 +/- 0.2 msec, the time constant of decay was 3.6 +/- 0.5 msec, and the mean amplitude of EPSC was -5.5 +/- 1.0 nA at the resting potential level (-53.8 +/- 1.4 mV) and at 36 degrees C. Amplitude of EPSC varied with membrane potential almost linearly at negative potentials, non-linearly at positive potentials, and nullified at -8.9 +/- 1.8 mV. The decay of EPSC was exponential over the most of its time course and the rate constant of decay (alpha) varied exponentially with membrane potential according to the relationship alpha(V) = B exp(AV), with A = 0.00716 +/- 0.00101 mV-1 and B = 0.46 +/- 0.07 msec-1. The voltage sensitivity of EPSC decay is interpreted in terms of voltage sensitivity in ionic channel lifetimes.", "contents": "Fast excitatory postsynaptic currents in voltage-clamped mammalian sympathetic ganglion neurones. Fast excitatory postsynaptic currents (EPSCs) were recorded in voltage-clamped neurones of isolated superior cervical ganglion of the rabbit. The rise time, decay time and whole duration of EPSC, as well as miniature EPSC, were shorter than those of corresponding postsynaptic potentials. Characteristic impedance for EPSC was 5.5 +/- 1.1 M omega, and was a few times lower than for current evoked by iontophoretic application of ACh. The rise time of EPSC was 2.0 +/- 0.2 msec, the time constant of decay was 3.6 +/- 0.5 msec, and the mean amplitude of EPSC was -5.5 +/- 1.0 nA at the resting potential level (-53.8 +/- 1.4 mV) and at 36 degrees C. Amplitude of EPSC varied with membrane potential almost linearly at negative potentials, non-linearly at positive potentials, and nullified at -8.9 +/- 1.8 mV. The decay of EPSC was exponential over the most of its time course and the rate constant of decay (alpha) varied exponentially with membrane potential according to the relationship alpha(V) = B exp(AV), with A = 0.00716 +/- 0.00101 mV-1 and B = 0.46 +/- 0.07 msec-1. The voltage sensitivity of EPSC decay is interpreted in terms of voltage sensitivity in ionic channel lifetimes."}
{"id": "PMID:233311", "title": "Classically conditioned heart rate responses in Macaca mulatta after beta-adrenergic, vagal and ganglionic blockade.", "content": "Heart rates of 5 rhesus monkeys (Macaca mulatta) were monitored during classical conditioning trials consisting of a visual conditioned stimulus followed after 10 sec by an electric shock to the tail. Heart rates typically increased at the onset of the visual stimulus, and returned to baseline before shock delivery. Autonomic blocking agents were subsequently administered; their effects on resting heart rates, and on acceleratory and deceleratory phases of the biphasic conditioned heart rate responses were examined, both in the raw data, and with a statistical regression technique. Beta-adrenergic blockade by propranolol lowered resting heart rates and was found, after regression analysis, to reduce the heart rate increase phase, and to weakly enhance the subsequent heart rate decrease phase of the conditioned response. Vagal blockade by atropine sulfate elevated resting heart rate, and markedly reduced both acceleratory and deceleratory heart rate phases of the conditioned responses. Ganglionic blockade by chlorisondamine also elevated resting heart rates (less than atropine), and almost completely eliminated conditioned heart rate changes. Several sources of evidence suggest a predominant vagal tone over resting heart rates, as well as mostly vagal mediation (with some sympathetic contribution) of the biphasic conditioned rate response.", "contents": "Classically conditioned heart rate responses in Macaca mulatta after beta-adrenergic, vagal and ganglionic blockade. Heart rates of 5 rhesus monkeys (Macaca mulatta) were monitored during classical conditioning trials consisting of a visual conditioned stimulus followed after 10 sec by an electric shock to the tail. Heart rates typically increased at the onset of the visual stimulus, and returned to baseline before shock delivery. Autonomic blocking agents were subsequently administered; their effects on resting heart rates, and on acceleratory and deceleratory phases of the biphasic conditioned heart rate responses were examined, both in the raw data, and with a statistical regression technique. Beta-adrenergic blockade by propranolol lowered resting heart rates and was found, after regression analysis, to reduce the heart rate increase phase, and to weakly enhance the subsequent heart rate decrease phase of the conditioned response. Vagal blockade by atropine sulfate elevated resting heart rate, and markedly reduced both acceleratory and deceleratory heart rate phases of the conditioned responses. Ganglionic blockade by chlorisondamine also elevated resting heart rates (less than atropine), and almost completely eliminated conditioned heart rate changes. Several sources of evidence suggest a predominant vagal tone over resting heart rates, as well as mostly vagal mediation (with some sympathetic contribution) of the biphasic conditioned rate response."}
{"id": "PMID:233312", "title": "Immunopotentiation and anabolism induced by sodium diethyldithiocarbamate.", "content": "Sodium diethyldithiocarbamate, DTC, enhances over a large range of doses macrophage listericidal capacity and T cell activities in terms of increased IgG-antibody forming spleen cells and delayed hypersensitivity levels. Such immunopotentiation is not associated with splenomegalia or increase in lymphocyte counts. Immunopotentiation requires a preexisting link between carbon disulfide and diethylamine, since both moieties were inactive if administered alone or on separate body sites. DTC demonstrates also an anabolic effect on mice emanciated by administering a B. melitensis cell-wall fraction. The role of DTC on hormonal production is discussed in relation to hormone-mediated action on T cell induction.", "contents": "Immunopotentiation and anabolism induced by sodium diethyldithiocarbamate. Sodium diethyldithiocarbamate, DTC, enhances over a large range of doses macrophage listericidal capacity and T cell activities in terms of increased IgG-antibody forming spleen cells and delayed hypersensitivity levels. Such immunopotentiation is not associated with splenomegalia or increase in lymphocyte counts. Immunopotentiation requires a preexisting link between carbon disulfide and diethylamine, since both moieties were inactive if administered alone or on separate body sites. DTC demonstrates also an anabolic effect on mice emanciated by administering a B. melitensis cell-wall fraction. The role of DTC on hormonal production is discussed in relation to hormone-mediated action on T cell induction."}
{"id": "PMID:233313", "title": "Thymic hormones.", "content": "The thymus produces several polypeptides, which induce lymphocyte differentiation in vitro and in vivo. Several of these polypeptides have been chemically characterized, and three of them have been sequenced and synthesised (alpha 1 thymosin, thymopoietin and the serum thymic factor). Thymic hormones do not act identically on all T-cell subsets: they alter preferentially post-thymic precursor cells, and among mature T cells cytotoxic cells and suppressor cells. Their mode of action at the cellular level involves binding to specific cellular receptors and interaction with adenyl cyclase. Preliminary clinical trials with crude extracts have provided promising results in immunodeficient and cancer patients. The differentiation of T cells from stem cells has been the matter of considerable investigation over the last two decades, since it has been realized that the thymus and its products, the thymus-derived cells (T cells) play a central role in the generation of effector cells in cell-mediated immunity and in the regulation of the various categories of immune responses. That the thymus could act by the intermediate of humoral substances was precociously suggested by MILLER and OSOBA before the observation that thymuses grafted within a cell-impermeable Millipore diffusion chamber restored the immunocompetence of neonatally thymectomized (Tx) mice (1). However, although this experiment was ultimately confirmed by using chambers with well-controlled impermeability (2), MILLER did not pursue the idea of the humoral function of the thymus. Probably, the striking results obtained by DAVIES (3) and other workers, indicating direct migration of functional T cells from the thymus and the poor results initially obtained in trying to reconstitute the immune system of neonatally Tx mice by cell-free thymic extracts contributed to this disappointment. A new impetus was given to the subject in the early 70's when in vitro tests of lymphocyte function became available and when purified extracts of the thymus proved capable of restoring antigen-specific and non-specific immunocompetence of Tx mice. More recently, completely defined synthetic thymic hormones have been obtained. The question is no longer to decide whether thymic hormones exist, but rather to elucidate their biological significance and potential clinical applications. The multiplicity of available factors has created some confusion. It will be the aim of these few pages to review critically the various factors reported in the literature, giving particular emphasis to their pharmacology and their potential use in the modulation of immune responses.", "contents": "Thymic hormones. The thymus produces several polypeptides, which induce lymphocyte differentiation in vitro and in vivo. Several of these polypeptides have been chemically characterized, and three of them have been sequenced and synthesised (alpha 1 thymosin, thymopoietin and the serum thymic factor). Thymic hormones do not act identically on all T-cell subsets: they alter preferentially post-thymic precursor cells, and among mature T cells cytotoxic cells and suppressor cells. Their mode of action at the cellular level involves binding to specific cellular receptors and interaction with adenyl cyclase. Preliminary clinical trials with crude extracts have provided promising results in immunodeficient and cancer patients. The differentiation of T cells from stem cells has been the matter of considerable investigation over the last two decades, since it has been realized that the thymus and its products, the thymus-derived cells (T cells) play a central role in the generation of effector cells in cell-mediated immunity and in the regulation of the various categories of immune responses. That the thymus could act by the intermediate of humoral substances was precociously suggested by MILLER and OSOBA before the observation that thymuses grafted within a cell-impermeable Millipore diffusion chamber restored the immunocompetence of neonatally thymectomized (Tx) mice (1). However, although this experiment was ultimately confirmed by using chambers with well-controlled impermeability (2), MILLER did not pursue the idea of the humoral function of the thymus. Probably, the striking results obtained by DAVIES (3) and other workers, indicating direct migration of functional T cells from the thymus and the poor results initially obtained in trying to reconstitute the immune system of neonatally Tx mice by cell-free thymic extracts contributed to this disappointment. A new impetus was given to the subject in the early 70's when in vitro tests of lymphocyte function became available and when purified extracts of the thymus proved capable of restoring antigen-specific and non-specific immunocompetence of Tx mice. More recently, completely defined synthetic thymic hormones have been obtained. The question is no longer to decide whether thymic hormones exist, but rather to elucidate their biological significance and potential clinical applications. The multiplicity of available factors has created some confusion. It will be the aim of these few pages to review critically the various factors reported in the literature, giving particular emphasis to their pharmacology and their potential use in the modulation of immune responses."}
{"id": "PMID:233314", "title": "Development, reactivity and GFA immunofluorescence of astroglia-containing monolayer cultures from rat cerebrum.", "content": "This report describes detailed protocols for the dissociation, seeding and growth in vitro of monolayer cultures derived from neonatal rat cerebrum. Primary cultures derived by using different seeding densities and in vitro ages were examined qualitatively and quantitatively for morphological composition in terms of two major cell classes (flat cells and process-bearing cells) and for the presence within these classes of glial fibrillary acidic protein (GFA) as detected by immunofluorescence histochemistry. Also examined was the reaction of the cells to serum withdrawal plus the administration of dibutyryl cyclic AMP in terms of the conversion of flat cells into process-bearing cells. Conditions are defined for the generation of in vitro cell populations, more than 90% of which are GFA-containing flat cells which can all be experimentally converted into cells with processes. These well-defined culture preparations will serve as useful models for future studies of astroglial behaviour.", "contents": "Development, reactivity and GFA immunofluorescence of astroglia-containing monolayer cultures from rat cerebrum. This report describes detailed protocols for the dissociation, seeding and growth in vitro of monolayer cultures derived from neonatal rat cerebrum. Primary cultures derived by using different seeding densities and in vitro ages were examined qualitatively and quantitatively for morphological composition in terms of two major cell classes (flat cells and process-bearing cells) and for the presence within these classes of glial fibrillary acidic protein (GFA) as detected by immunofluorescence histochemistry. Also examined was the reaction of the cells to serum withdrawal plus the administration of dibutyryl cyclic AMP in terms of the conversion of flat cells into process-bearing cells. Conditions are defined for the generation of in vitro cell populations, more than 90% of which are GFA-containing flat cells which can all be experimentally converted into cells with processes. These well-defined culture preparations will serve as useful models for future studies of astroglial behaviour."}
{"id": "PMID:233315", "title": "Naturally-occurring neoplasms in the Mongolian gerbil, Meriones unguiculatus.", "content": "10 spontaneous tumours were observed. Several had not been previously reported for this species and 1 occurred in the youngest gerbil yet reported to have a spontaneous tumour. 7 of the 10 tumours originated from the female reproductive tract.", "contents": "Naturally-occurring neoplasms in the Mongolian gerbil, Meriones unguiculatus. 10 spontaneous tumours were observed. Several had not been previously reported for this species and 1 occurred in the youngest gerbil yet reported to have a spontaneous tumour. 7 of the 10 tumours originated from the female reproductive tract."}
{"id": "PMID:233317", "title": "Effects of polybrominated biphenyl on a discrimination task in rats.", "content": "Learning or performance of an operant discrimination task by laboratory rats in Skinner boxes was studied as a function of subchronic treatment with polybrominated biphenyl (PBB) (1.0 mg/kg, 3.0 mg/kg or 6.0 mg/kg for 20 days). Acquisition of the discrimination task was similar for experimental and control rats at each dose level. Response times were slower for the 1.0 mg/kg rats but were like controls for the 3.0 and 6.0 mg/kg animals. Extra responses occurring in the absence of auditory discriminative stimuli increased significantly for the 1.0 mg/kg rats (hyperactivity), were no different from controls for the 3.0 mg/kg rats and decreased significantly for the 6.0 mg/kg animals (CNS depression). The weights of PBB animals did not differ significantly from controls. Analyses of brains and plasma by electron capture gas chromatography yielded detectable levels of PBB as long as 10 months following the last PBB administration. PBB in brains and plasma varied directly as a function of dose administered.", "contents": "Effects of polybrominated biphenyl on a discrimination task in rats. Learning or performance of an operant discrimination task by laboratory rats in Skinner boxes was studied as a function of subchronic treatment with polybrominated biphenyl (PBB) (1.0 mg/kg, 3.0 mg/kg or 6.0 mg/kg for 20 days). Acquisition of the discrimination task was similar for experimental and control rats at each dose level. Response times were slower for the 1.0 mg/kg rats but were like controls for the 3.0 and 6.0 mg/kg animals. Extra responses occurring in the absence of auditory discriminative stimuli increased significantly for the 1.0 mg/kg rats (hyperactivity), were no different from controls for the 3.0 mg/kg rats and decreased significantly for the 6.0 mg/kg animals (CNS depression). The weights of PBB animals did not differ significantly from controls. Analyses of brains and plasma by electron capture gas chromatography yielded detectable levels of PBB as long as 10 months following the last PBB administration. PBB in brains and plasma varied directly as a function of dose administered."}
{"id": "PMID:233318", "title": "Correlation of systemic and biochemical effects of PBB with behavioral effects.", "content": "Rats were given PBB orally at 1, 3, and 6 mg/kg (or vehicle as control) daily for 20 days. Some animals were sacrificed immediately while the food intake of remaining animals was limited to attain and maintain 80% of normal body weight. No effect of PBB upon body weight was observed for any of the dose levels employed. Immediately after dosing, liver/body weight ratios were 110% of controls for the 1 mg/kg group and 152% for the 3 and 6 mg/kg groups; after weight reduction for 2-6 months liver/body weight ratios for all 3 dose groups were 160-170% of controls. In the absence of body fat, most tissues exhibited dose-dependent retention of PBB 2-6 months after dosing with highest levels in liver followed by kidney. In 6 mg/kg rats weight-reduced for 6 months, liver AHH activity was 613% of controls; in rats sacrificed immediately after dosing, liver AHH activity was dose-related but appeared to reach maximal value at the 3 mg/kg dose. Both calcium binding to synaptic plasma membranes and calcium uptake by intact synaptosomes was significantly reduced in the brains of 1 mg/kg PBB rats, but not affected in preparations from 3 and 6 mg/kg animals.", "contents": "Correlation of systemic and biochemical effects of PBB with behavioral effects. Rats were given PBB orally at 1, 3, and 6 mg/kg (or vehicle as control) daily for 20 days. Some animals were sacrificed immediately while the food intake of remaining animals was limited to attain and maintain 80% of normal body weight. No effect of PBB upon body weight was observed for any of the dose levels employed. Immediately after dosing, liver/body weight ratios were 110% of controls for the 1 mg/kg group and 152% for the 3 and 6 mg/kg groups; after weight reduction for 2-6 months liver/body weight ratios for all 3 dose groups were 160-170% of controls. In the absence of body fat, most tissues exhibited dose-dependent retention of PBB 2-6 months after dosing with highest levels in liver followed by kidney. In 6 mg/kg rats weight-reduced for 6 months, liver AHH activity was 613% of controls; in rats sacrificed immediately after dosing, liver AHH activity was dose-related but appeared to reach maximal value at the 3 mg/kg dose. Both calcium binding to synaptic plasma membranes and calcium uptake by intact synaptosomes was significantly reduced in the brains of 1 mg/kg PBB rats, but not affected in preparations from 3 and 6 mg/kg animals."}
{"id": "PMID:233322", "title": "Collagen synthesis in the developing chick heart.", "content": "We have surveyed the amount and types of collagen synthesized in two regions of the chick heart during embryonic development. Cardiac tissues from successive periods of development were labeled with 3H-proline in short-term organ culture. The fraction of incorporated label present as collagen was estimated by comparison of TCA-soluble radioactivity before and after digestion with purified bacterial collagenase. This measure of collagen synthesis varied only slightly with the length of the labeling period and agreed with values obtained by labeling in ovo. In the developing outflow tract, the fraction of label present as collagen increased sharply during the period of truncal septation (5-9 days), rising from initial values of 6% at 3 days of incubation to a plateau of about 25% (10-19 days). In ventricular myocardium, this fraction rose gradually from 3 to 20% between 3 and 19 days of incubation. The types of collagen synthesized in developing heart were analyzed by limited pepsin digestion and acrylamide gel electrophoresis, using collagens synthesized in tendon, cartilage, skin, and lens capsule for comparison. The types of collagen synthesized in both cardiac regions changed in similar manner during development. During the first week of cardiac function, a substantial but progressively smaller fraction of total collagen synthesized was identified as Type IV. Synthesis of Type I collagen increased sharply during this period and predominated during the second half of development. Type III collagen was synthesized in trace amounts by the middle of development and constituted approximately one-sixth of total collagen synthesis just before hatching. Minor amounts of collagen identified as Type B collagen were synthesized throughout the latter two-thirds of development.", "contents": "Collagen synthesis in the developing chick heart. We have surveyed the amount and types of collagen synthesized in two regions of the chick heart during embryonic development. Cardiac tissues from successive periods of development were labeled with 3H-proline in short-term organ culture. The fraction of incorporated label present as collagen was estimated by comparison of TCA-soluble radioactivity before and after digestion with purified bacterial collagenase. This measure of collagen synthesis varied only slightly with the length of the labeling period and agreed with values obtained by labeling in ovo. In the developing outflow tract, the fraction of label present as collagen increased sharply during the period of truncal septation (5-9 days), rising from initial values of 6% at 3 days of incubation to a plateau of about 25% (10-19 days). In ventricular myocardium, this fraction rose gradually from 3 to 20% between 3 and 19 days of incubation. The types of collagen synthesized in developing heart were analyzed by limited pepsin digestion and acrylamide gel electrophoresis, using collagens synthesized in tendon, cartilage, skin, and lens capsule for comparison. The types of collagen synthesized in both cardiac regions changed in similar manner during development. During the first week of cardiac function, a substantial but progressively smaller fraction of total collagen synthesized was identified as Type IV. Synthesis of Type I collagen increased sharply during this period and predominated during the second half of development. Type III collagen was synthesized in trace amounts by the middle of development and constituted approximately one-sixth of total collagen synthesis just before hatching. Minor amounts of collagen identified as Type B collagen were synthesized throughout the latter two-thirds of development."}
{"id": "PMID:233324", "title": "Role of cyclic AMP in myocardial cell function.", "content": "A series of agents which stimulate the formation of cyclic AMP are well-known positive inotropic agents in the heart. This fact has suggested that cyclic AMP may indeed mediate the positive inotropic effects. The elucidation of precise in vivo mechanisms utilizing in vitro and isolated techniques is always difficult; in the myocardial cell, a very complicated and multicompartmented cell, all such in vivo-in vitro correlation must be viewed with caution. In this review, the authors has attempted to list possible cellular sites of inotropic intervention based on current concepts of excitation contraction coupling (which also are speculative). Recent evidence from in vitro experiments have suggested several sites which are apparently affected by cyclic AMP-mediated events and which are thought to be intimately related to the control of myocardial contraction. It is suggested that the myocardium be viewed as a multicompartmented system with several effector sites for cyclic AMP-mediated events, all of which have individual controls; this type of thesis would be necessary to explain the volume of experimental data which fails to show simple correlation between myocardial cyclic AMP levels and cardiac contractility. The difficulties in designing experiments to further elucidate these mechanisms and the possibility of \"linked enzyme systems\" are also discussed.", "contents": "Role of cyclic AMP in myocardial cell function. A series of agents which stimulate the formation of cyclic AMP are well-known positive inotropic agents in the heart. This fact has suggested that cyclic AMP may indeed mediate the positive inotropic effects. The elucidation of precise in vivo mechanisms utilizing in vitro and isolated techniques is always difficult; in the myocardial cell, a very complicated and multicompartmented cell, all such in vivo-in vitro correlation must be viewed with caution. In this review, the authors has attempted to list possible cellular sites of inotropic intervention based on current concepts of excitation contraction coupling (which also are speculative). Recent evidence from in vitro experiments have suggested several sites which are apparently affected by cyclic AMP-mediated events and which are thought to be intimately related to the control of myocardial contraction. It is suggested that the myocardium be viewed as a multicompartmented system with several effector sites for cyclic AMP-mediated events, all of which have individual controls; this type of thesis would be necessary to explain the volume of experimental data which fails to show simple correlation between myocardial cyclic AMP levels and cardiac contractility. The difficulties in designing experiments to further elucidate these mechanisms and the possibility of \"linked enzyme systems\" are also discussed."}
{"id": "PMID:233325", "title": "Endocrine interaction of the thymus with the hypohysis, adrenals and testes: effects of two thymic extracts.", "content": "The concentration of ACTH, corticosterone, LH and testosterone in the plasma of rats have been measured in normal, thymectomized and sham-operated rats. A group of rats, thymectomized at birth, received two i.p. injections weekly of two thymic extracts, each prepared in a separate way. Neonatal thymectomy was followed by the appearance of a transitory wasting disease during which a hormonal unbalance was manifest. Plasma corticosterone and ACTH levels increased at first at 30 days after thymectomy and then decreased at 60 days. The levels of the different hormones returned to normal by 90 days. The injections of thymic extracts rectified all these perturbations. The plasma levels of testosterone and corticosterone of hypophysectomized rats were compared to those of hypophysectomized and thymectomized animals. Results suggested that the thymus has a direct action of the adrenal cortex and in indirect action on the testes. The indirect effect is probably mediated through the hypophysis.", "contents": "Endocrine interaction of the thymus with the hypohysis, adrenals and testes: effects of two thymic extracts. The concentration of ACTH, corticosterone, LH and testosterone in the plasma of rats have been measured in normal, thymectomized and sham-operated rats. A group of rats, thymectomized at birth, received two i.p. injections weekly of two thymic extracts, each prepared in a separate way. Neonatal thymectomy was followed by the appearance of a transitory wasting disease during which a hormonal unbalance was manifest. Plasma corticosterone and ACTH levels increased at first at 30 days after thymectomy and then decreased at 60 days. The levels of the different hormones returned to normal by 90 days. The injections of thymic extracts rectified all these perturbations. The plasma levels of testosterone and corticosterone of hypophysectomized rats were compared to those of hypophysectomized and thymectomized animals. Results suggested that the thymus has a direct action of the adrenal cortex and in indirect action on the testes. The indirect effect is probably mediated through the hypophysis."}
{"id": "PMID:233335", "title": "Analysis of the electron spin resonance spectrum of human liver tissue embedded in paraffin.", "content": "The ESR spectra of the liver samples embedded in paraffin of newborn, adult, cirrhotic and control individuals always display the g approximately 2.05 signal and occasionally also the g = 4.3 line and the signal of free radicals. In adults, the amplitude of the g approximately 2.05 signal is negatively correlated with that of the g approximately 4.3 signal; in infants aged from three months to one year this correlation is positive. The copper content of the liver is in linear correlation with the amplitude of the g approximately 2.05 signal. The hyperfine structure of the part of the g approximately 2.05 signal recorded at low magnetic field may be of three types: it may correspond to Cu2+ centers of axial symmetry of type I, II or I + II. The parameters of the signal are the following: type I center, g = 2.35 +/- 0.05, g = 2.05 +/- 0.01, A < 100 gauss; type II center, g = 2.25 +/- 0.03, g = 2.05 +/- 0.01, A = 160 +/- 20 gauss. On the basis of the amplitude of the g approximately 2.05 signal, the copper content of the liver tissue can be estimated from paraffin blocks with an error of 30%, without losing the tissue embedded for histological examination.", "contents": "Analysis of the electron spin resonance spectrum of human liver tissue embedded in paraffin. The ESR spectra of the liver samples embedded in paraffin of newborn, adult, cirrhotic and control individuals always display the g approximately 2.05 signal and occasionally also the g = 4.3 line and the signal of free radicals. In adults, the amplitude of the g approximately 2.05 signal is negatively correlated with that of the g approximately 4.3 signal; in infants aged from three months to one year this correlation is positive. The copper content of the liver is in linear correlation with the amplitude of the g approximately 2.05 signal. The hyperfine structure of the part of the g approximately 2.05 signal recorded at low magnetic field may be of three types: it may correspond to Cu2+ centers of axial symmetry of type I, II or I + II. The parameters of the signal are the following: type I center, g = 2.35 +/- 0.05, g = 2.05 +/- 0.01, A < 100 gauss; type II center, g = 2.25 +/- 0.03, g = 2.05 +/- 0.01, A = 160 +/- 20 gauss. On the basis of the amplitude of the g approximately 2.05 signal, the copper content of the liver tissue can be estimated from paraffin blocks with an error of 30%, without losing the tissue embedded for histological examination."}
{"id": "PMID:233337", "title": "Treatment of the Lennox syndrome with ACTH: a clinical and electroencephalographic study.", "content": "In 45 cases of Lennox syndrome treated with ACTH, the immediate and long-term effects and the various factors affecting them were investigated by a follow-up study. 1) Regarding the immediate effect, 23 (51.1%) of the 45 cases became \"seizure free\" for over 10 days. 2) As to the long-term prognosis of these 23 cases, 10 cases relapsed into Lennox syndrome within 6 months and in the remaining 13 cases, seizures were suppressed for over 6 months; out of these 13, seizure relapse was observed in eight cases from 9 months to 7 years later, and the other five cases followed a very favorable course without relapse. 3) The favorable factors related to the effect of ACTH for Lennox syndrome are: a) age at ACTH treatment: up to 4 years old, b) time lag between onset of Lennox syndrome and initiation of ACTH treatment: the shorter the better; at least within 1 year, preferably within 3 months, c) presumptive causes and underlying diseases: idiopathic cases are best, d) mental defects before treatment: the slighter the better, e) seizure patterns: without tonic seizures, and f) EEG findings: disorganized diffuse slow spike-waves without asymmetry. 4) It is desirable to continue the ACTH treatment as long as possible, with the goal of the disappearance of seizure discharges, or at least the disappearance of diffuse seizure discharges.", "contents": "Treatment of the Lennox syndrome with ACTH: a clinical and electroencephalographic study. In 45 cases of Lennox syndrome treated with ACTH, the immediate and long-term effects and the various factors affecting them were investigated by a follow-up study. 1) Regarding the immediate effect, 23 (51.1%) of the 45 cases became \"seizure free\" for over 10 days. 2) As to the long-term prognosis of these 23 cases, 10 cases relapsed into Lennox syndrome within 6 months and in the remaining 13 cases, seizures were suppressed for over 6 months; out of these 13, seizure relapse was observed in eight cases from 9 months to 7 years later, and the other five cases followed a very favorable course without relapse. 3) The favorable factors related to the effect of ACTH for Lennox syndrome are: a) age at ACTH treatment: up to 4 years old, b) time lag between onset of Lennox syndrome and initiation of ACTH treatment: the shorter the better; at least within 1 year, preferably within 3 months, c) presumptive causes and underlying diseases: idiopathic cases are best, d) mental defects before treatment: the slighter the better, e) seizure patterns: without tonic seizures, and f) EEG findings: disorganized diffuse slow spike-waves without asymmetry. 4) It is desirable to continue the ACTH treatment as long as possible, with the goal of the disappearance of seizure discharges, or at least the disappearance of diffuse seizure discharges."}
{"id": "PMID:233338", "title": "Ultrastructural pathology of lymphocytes in neuronal ceroid-lipofuscinoses.", "content": "Lymphocytes were studied by electron microscopy in five cases of neuronal ceroid-lipofuscinoses (NCL), one of infantile, three of late infantile and one of juvenile types. Each type of NCL revealed specific cytoplasmic inclusions, namely, granular bodies in the infantile form, curvilinear profiles in the late infantile form and fingerprint profiles within vacuoles in the juvenile type. Survey of the literature also confirmed the high correlation between subtype of NCL and type of lymphocytic inclusion. The electron microscopic examination lymphocytes offers easily available diagnostic informations.", "contents": "Ultrastructural pathology of lymphocytes in neuronal ceroid-lipofuscinoses. Lymphocytes were studied by electron microscopy in five cases of neuronal ceroid-lipofuscinoses (NCL), one of infantile, three of late infantile and one of juvenile types. Each type of NCL revealed specific cytoplasmic inclusions, namely, granular bodies in the infantile form, curvilinear profiles in the late infantile form and fingerprint profiles within vacuoles in the juvenile type. Survey of the literature also confirmed the high correlation between subtype of NCL and type of lymphocytic inclusion. The electron microscopic examination lymphocytes offers easily available diagnostic informations."}
{"id": "PMID:233340", "title": "The role of superoxide anion generation in antibody-dependent polymorphonuclear leukocyte-mediated cytotoxicity.", "content": "Human polymorphonuclear leukocytes (PMNs) can act as killer cells in an antibody-dependent cellular cytotoxicity (ADCC) system. Cytolysis is rapid and detectable at low effector/target cell ratios. PMNs from a patient affected by chronic granulomatous disease (CGD) exhibit an absolute defect in ADCC. In order to investigate the role of the toxic oxygen derivatives (H2O2 and superoxide anions) lacking in CGD, experiments in presence of specific inhibitors were carried out. Superoxide dismutase, an O-2 scavenger, displayed a significant inhibition activity in a dose dependent way. On the other hand neither catalase, which degrades H2O2, nor sodium azide, a myeloperoxidae inhibitor, affect the cytotoxic activity. Our results suggest that the importance of the intact oxidative metabolism in PMN-mediated ADCC against chicken red blood cells could be referred to the correlated production of O-2 anions.", "contents": "The role of superoxide anion generation in antibody-dependent polymorphonuclear leukocyte-mediated cytotoxicity. Human polymorphonuclear leukocytes (PMNs) can act as killer cells in an antibody-dependent cellular cytotoxicity (ADCC) system. Cytolysis is rapid and detectable at low effector/target cell ratios. PMNs from a patient affected by chronic granulomatous disease (CGD) exhibit an absolute defect in ADCC. In order to investigate the role of the toxic oxygen derivatives (H2O2 and superoxide anions) lacking in CGD, experiments in presence of specific inhibitors were carried out. Superoxide dismutase, an O-2 scavenger, displayed a significant inhibition activity in a dose dependent way. On the other hand neither catalase, which degrades H2O2, nor sodium azide, a myeloperoxidae inhibitor, affect the cytotoxic activity. Our results suggest that the importance of the intact oxidative metabolism in PMN-mediated ADCC against chicken red blood cells could be referred to the correlated production of O-2 anions."}
{"id": "PMID:233341", "title": "Complement fixing antibody to varicella-zoster virus in cancerous patients.", "content": "The titer of complement fixing antibody to Varicella-Zoster virus was studied in sera from 161 cancerous patients and 161 healthy controls. Sera with antibody titers greater than or equal to 1/4 were 74 (45.9%) among cancerous patients and 120 (74.5%) among healthy controls. The difference between these two groups is statistically significant.", "contents": "Complement fixing antibody to varicella-zoster virus in cancerous patients. The titer of complement fixing antibody to Varicella-Zoster virus was studied in sera from 161 cancerous patients and 161 healthy controls. Sera with antibody titers greater than or equal to 1/4 were 74 (45.9%) among cancerous patients and 120 (74.5%) among healthy controls. The difference between these two groups is statistically significant."}
{"id": "PMID:233342", "title": "[Enzymes of purine metabolism in the nuchal muscle (M. complexus) of chick embryo].", "content": "The developmental patterns of enzyme activities related to GMP metabolism have been investigated in chick embryo musculus complexus (m. Complexus). Guanylate phosphatase activity increases conspicuously from 18th to 21st day, guanosine phosphorylase increases on the 21st day and the guanase shows a very low activity during the whole period considered. Xanthine oxidase was always found absent. The results suggest that during the first period of incubation GMP breakdown in chick embryo m. complexus might follow a catabolic pathway, while starting from the 18th day some guanine might be converted to GMP originating a new metabolic pathway as previously suggested for AMP metabolism.", "contents": "[Enzymes of purine metabolism in the nuchal muscle (M. complexus) of chick embryo]. The developmental patterns of enzyme activities related to GMP metabolism have been investigated in chick embryo musculus complexus (m. Complexus). Guanylate phosphatase activity increases conspicuously from 18th to 21st day, guanosine phosphorylase increases on the 21st day and the guanase shows a very low activity during the whole period considered. Xanthine oxidase was always found absent. The results suggest that during the first period of incubation GMP breakdown in chick embryo m. complexus might follow a catabolic pathway, while starting from the 18th day some guanine might be converted to GMP originating a new metabolic pathway as previously suggested for AMP metabolism."}
{"id": "PMID:233343", "title": "[Interference of antioxidants E/O of some free radical \"scavengers\" with the activity of glucose-6-phosphatase after administration of carbon tetrachloride].", "content": "G-6-Pase activity was investigated in the microsomal fraction from rat liver in the presence of carbon tetrachloride and/or propyl gallate (PG), reduced glutathione (GSH) and superoxide dismutase. Results obtained \"in vitro\" demonstrated that CCl4 induced a 60% inhibition of the microsomal enzyme activity. Moreover, a marked inhibition of G-6-Pase activity was found also when propyl gallate and reduced glutathione were added, at different concentrations, to incubation mixture. In addition, these drugs were unable to interfere with the dangerous effect exerted on the enzymatic activity by the haloalkane. Additional experiments carried out \"in vivo\" with propyl gallate produced evidence that intraperitoneal administration of the antioxidant was followed by a significant inhibition of G-6-Pase activity, while the damaging action of CCl4 was unaffected. Some possible explanations of these results are reported.", "contents": "[Interference of antioxidants E/O of some free radical \"scavengers\" with the activity of glucose-6-phosphatase after administration of carbon tetrachloride]. G-6-Pase activity was investigated in the microsomal fraction from rat liver in the presence of carbon tetrachloride and/or propyl gallate (PG), reduced glutathione (GSH) and superoxide dismutase. Results obtained \"in vitro\" demonstrated that CCl4 induced a 60% inhibition of the microsomal enzyme activity. Moreover, a marked inhibition of G-6-Pase activity was found also when propyl gallate and reduced glutathione were added, at different concentrations, to incubation mixture. In addition, these drugs were unable to interfere with the dangerous effect exerted on the enzymatic activity by the haloalkane. Additional experiments carried out \"in vivo\" with propyl gallate produced evidence that intraperitoneal administration of the antioxidant was followed by a significant inhibition of G-6-Pase activity, while the damaging action of CCl4 was unaffected. Some possible explanations of these results are reported."}
{"id": "PMID:233345", "title": "[Histoenzymatic research and internal irradiation. V. Histochemical modifications in rat liver with the use of colloidal Au198].", "content": "The histochemical behaviour of succinic dehydrogenase, isocitric dehydrogenase, acid phosphatase and acetylglucosaminidase activities was studied in rat liver treated with Au198-colloidal. In these experimental conditions it was found that the hepatocytes present changes in the enzymatic activities examined, generally proportional to the doses employed. With lower doses of radionuclides, the histoenzymatic changes have a local character and are completely reversible after a month. With higher doses they take on a more extensive character. These findings suggest that Au198 could be used clinically with due precautions.", "contents": "[Histoenzymatic research and internal irradiation. V. Histochemical modifications in rat liver with the use of colloidal Au198]. The histochemical behaviour of succinic dehydrogenase, isocitric dehydrogenase, acid phosphatase and acetylglucosaminidase activities was studied in rat liver treated with Au198-colloidal. In these experimental conditions it was found that the hepatocytes present changes in the enzymatic activities examined, generally proportional to the doses employed. With lower doses of radionuclides, the histoenzymatic changes have a local character and are completely reversible after a month. With higher doses they take on a more extensive character. These findings suggest that Au198 could be used clinically with due precautions."}
{"id": "PMID:233346", "title": "[DNA-protein interactions. Destabilizing activity of sheep pancreatic RNAase].", "content": "Evidence is presented that ovine pancreatic ribonuclease, a protein strictly homologous to bovine RNAase A but with one positive charge less, has a definite 'destabilizing' activity (quite similar to that of the bovine enzyme) on double-stranded DNA. This action of sheep pancreas RNAase has been measured by differential spectrophotometry and determining the thermal-transition profiles of the protein-DNA complexes.", "contents": "[DNA-protein interactions. Destabilizing activity of sheep pancreatic RNAase]. Evidence is presented that ovine pancreatic ribonuclease, a protein strictly homologous to bovine RNAase A but with one positive charge less, has a definite 'destabilizing' activity (quite similar to that of the bovine enzyme) on double-stranded DNA. This action of sheep pancreas RNAase has been measured by differential spectrophotometry and determining the thermal-transition profiles of the protein-DNA complexes."}
{"id": "PMID:233347", "title": "[Activity of glucose-6-phosphatase during liver regeneration].", "content": "During hepatic regeneration a drop in the liver glycogen content along with a lower blood glucose level have been observed. These data are difficult to correlate with the rise of blood glucagon and the drop of insulin shown at the same times after partial hepatectomy. Therefore, liver glucose-6-phosphatase activity has been studied at 1.5, 4, 15 and 24 h, since that enzyme is involved in the release of glucose from the cell. 4 and 15 h after partial hepatectomy a remarkable decrease in glucose-6-phosphatase activity is observed. These results are discussed in view of the higher metabolic demand of regenerating liver.", "contents": "[Activity of glucose-6-phosphatase during liver regeneration]. During hepatic regeneration a drop in the liver glycogen content along with a lower blood glucose level have been observed. These data are difficult to correlate with the rise of blood glucagon and the drop of insulin shown at the same times after partial hepatectomy. Therefore, liver glucose-6-phosphatase activity has been studied at 1.5, 4, 15 and 24 h, since that enzyme is involved in the release of glucose from the cell. 4 and 15 h after partial hepatectomy a remarkable decrease in glucose-6-phosphatase activity is observed. These results are discussed in view of the higher metabolic demand of regenerating liver."}
{"id": "PMID:233348", "title": "[Demonstration by immunofluorescence and immunoperoxidase of an antigen of the measles type in the osteoclasts of Paget's disease of bone].", "content": "The intra nuclear and intra cytoplasmic inclusions described in osteoclasts in PAGET's bone disease are morphologically similar to those observed in subacute sclerosing panencephalitis. Immunological techniques using different specific immune sera demonstrate the presence of an antigenic structure of viral origin in osteoclasts in PAGET's bone disease. A measles or a measles like virus is most likely to be involved and may play a role in the etiology of the disease.", "contents": "[Demonstration by immunofluorescence and immunoperoxidase of an antigen of the measles type in the osteoclasts of Paget's disease of bone]. The intra nuclear and intra cytoplasmic inclusions described in osteoclasts in PAGET's bone disease are morphologically similar to those observed in subacute sclerosing panencephalitis. Immunological techniques using different specific immune sera demonstrate the presence of an antigenic structure of viral origin in osteoclasts in PAGET's bone disease. A measles or a measles like virus is most likely to be involved and may play a role in the etiology of the disease."}
{"id": "PMID:233351", "title": "[Retroperitoneal tumors in children: clinical diagnostic problems (author's transl)].", "content": "Starting from two recent observations of retroperitoneal tumors in the pediatric age group (a nephroblastoma and a ganglioneuroma), the authors illustrate the main characteristics of these malignancies and emphasize the difficulties often encountered in differential diagnosis.", "contents": "[Retroperitoneal tumors in children: clinical diagnostic problems (author's transl)]. Starting from two recent observations of retroperitoneal tumors in the pediatric age group (a nephroblastoma and a ganglioneuroma), the authors illustrate the main characteristics of these malignancies and emphasize the difficulties often encountered in differential diagnosis."}
{"id": "PMID:233352", "title": "Protein degradation in health and disease. Introduction: the classification of proteinases.", "content": "Twenty years after B.S. Hartley's 1960 review, on which the present scheme for classification of the proteinases is based, most of the new information that has been obtained appears fully consistent with Hartley's views. A slight amendment is proposed of the name of the four groups of these enzymes to 'serine', 'cysteine', 'aspartic' and 'metallo'-proteinases.", "contents": "Protein degradation in health and disease. Introduction: the classification of proteinases. Twenty years after B.S. Hartley's 1960 review, on which the present scheme for classification of the proteinases is based, most of the new information that has been obtained appears fully consistent with Hartley's views. A slight amendment is proposed of the name of the four groups of these enzymes to 'serine', 'cysteine', 'aspartic' and 'metallo'-proteinases."}
{"id": "PMID:233353", "title": "Regulation of protein breakdown in hepatocyte monolayers.", "content": "Effects of potential modifiers on intracellular protein degradation have been measured in hepatocyte monolayers two days after the cells were isolated and plated. Modifiers were added after cells had been labelled with [3H]leucine and generally at the beginning of the degradation period. Protein degradation was inhibited by insulin, epidermal growth factor and serum as well as the protein synthesis inhibitors, leupeptin and weak bases. Degradation was stimulated by cyclic AMP, glucagon, beta-agonists, glucocorticoids and nutritional stepdown. The results from addition and competition experiments are consistent with all effectors acting on lysosomal proteolysis but differing in whether they alter amounts of proteinases, conditions favourable for proteinase function, or degree of autophagocytosis.", "contents": "Regulation of protein breakdown in hepatocyte monolayers. Effects of potential modifiers on intracellular protein degradation have been measured in hepatocyte monolayers two days after the cells were isolated and plated. Modifiers were added after cells had been labelled with [3H]leucine and generally at the beginning of the degradation period. Protein degradation was inhibited by insulin, epidermal growth factor and serum as well as the protein synthesis inhibitors, leupeptin and weak bases. Degradation was stimulated by cyclic AMP, glucagon, beta-agonists, glucocorticoids and nutritional stepdown. The results from addition and competition experiments are consistent with all effectors acting on lysosomal proteolysis but differing in whether they alter amounts of proteinases, conditions favourable for proteinase function, or degree of autophagocytosis."}
{"id": "PMID:233354", "title": "Human collagenases: comparative and immunolocalization studies.", "content": "Four human collagenases derived from different tissues or cells were shown to have different physicochemical properties with regard to molecular size and protein charge. Such differences have been used to demonstrate that the collagenase activity of rheumatoid synovial fluids is of granulocytic origin. Immunolocalization studies have demonstrated that immunoreactive collagenase is present in a variety of human tissues. Its production by cells in normal tissues suggests a role in collagen remodelling processes, whereas its more frequent occurrence in diseased tissues suggests an important role in pathological collagen resorption. In nearly all the positive specimens examined the enzyme was restricted to a single cell or small groups of cells, or collagenous elements, suggesting microenvironmental rather than widespread collagenolytic activity.", "contents": "Human collagenases: comparative and immunolocalization studies. Four human collagenases derived from different tissues or cells were shown to have different physicochemical properties with regard to molecular size and protein charge. Such differences have been used to demonstrate that the collagenase activity of rheumatoid synovial fluids is of granulocytic origin. Immunolocalization studies have demonstrated that immunoreactive collagenase is present in a variety of human tissues. Its production by cells in normal tissues suggests a role in collagen remodelling processes, whereas its more frequent occurrence in diseased tissues suggests an important role in pathological collagen resorption. In nearly all the positive specimens examined the enzyme was restricted to a single cell or small groups of cells, or collagenous elements, suggesting microenvironmental rather than widespread collagenolytic activity."}
{"id": "PMID:233355", "title": "Proteinases in connective tissue breakdown.", "content": "Lysosomal cathepsins B and N complete the depolymerization of native fibrillar collagen in the phagolysosome after prior extracellular fragmentation by collagenase and other neutral proteinases. In vitro studies have confirmed that cathepsins B and N cleave native collagen only at the short non-helical telopeptides, which generate the intermolecular cross-links. This action occurs maximally at pH 3.5 and at 37 degrees C the released monomers denature spontaneously and are susceptible to further breakdown. In the phagolysosome the collagenous debris is already weakened and probably therefore, more easily disrupted by these cathepsins. Complete digestion would then be undertaken by the whole complement of proteases. The lysosomal glycosidases may assist this breakdown by degrading ground substance components which are normally tightly bound to collagen. In certain situations cells may instead generate an acidic pericellular environment that could permit the direct action of secreted lysosomal enzymes. This extracellular action may supersede the action of collagenase and the activity of these different enzymes would thus be regulated by changes in the nature of this microenvironment.", "contents": "Proteinases in connective tissue breakdown. Lysosomal cathepsins B and N complete the depolymerization of native fibrillar collagen in the phagolysosome after prior extracellular fragmentation by collagenase and other neutral proteinases. In vitro studies have confirmed that cathepsins B and N cleave native collagen only at the short non-helical telopeptides, which generate the intermolecular cross-links. This action occurs maximally at pH 3.5 and at 37 degrees C the released monomers denature spontaneously and are susceptible to further breakdown. In the phagolysosome the collagenous debris is already weakened and probably therefore, more easily disrupted by these cathepsins. Complete digestion would then be undertaken by the whole complement of proteases. The lysosomal glycosidases may assist this breakdown by degrading ground substance components which are normally tightly bound to collagen. In certain situations cells may instead generate an acidic pericellular environment that could permit the direct action of secreted lysosomal enzymes. This extracellular action may supersede the action of collagenase and the activity of these different enzymes would thus be regulated by changes in the nature of this microenvironment."}
{"id": "PMID:233356", "title": "Natural history of perinatal cytomegaloviral infection.", "content": "Epidemiological data presented here indicate that cytomegaloviral (CMV) infection is one of the most common perinatal infections found in human beings. Transmission to the offspring occurs in utero at birth and postnatally. Intrauterine infection results from primary or recurrent maternal involvement, the latter being more common in populations where infection is initially acquired during childhood or adolescence, such as in low socioeconomic settings. Congenital infection is usually subclinical with either type of maternal involvement but primary infection has a greater tendency to produce disease in the fetus. About 20% of the offspring infected in utero are damaged, infrequently with generalized disease, but more often with auditory involvement. The latter can develop in utero or postnatally and can be progressive. The major cause of recurrent maternal infection according to restriction enzyme analysis is reactivation of latent virus, which occurs in the face of substantial maternal humoral immunity, even with intrauterine transmission of virus. Reinfection by exogenous virus remains a lesser possibility for maternal recurrences. Even more commonly, CMV can be transmitted at birth from the infected maternal genital tract and postnatally through infected breast milk, especially in highly immune populations. With the possible exception of early pneumonia, these infections appear to be innocuous.", "contents": "Natural history of perinatal cytomegaloviral infection. Epidemiological data presented here indicate that cytomegaloviral (CMV) infection is one of the most common perinatal infections found in human beings. Transmission to the offspring occurs in utero at birth and postnatally. Intrauterine infection results from primary or recurrent maternal involvement, the latter being more common in populations where infection is initially acquired during childhood or adolescence, such as in low socioeconomic settings. Congenital infection is usually subclinical with either type of maternal involvement but primary infection has a greater tendency to produce disease in the fetus. About 20% of the offspring infected in utero are damaged, infrequently with generalized disease, but more often with auditory involvement. The latter can develop in utero or postnatally and can be progressive. The major cause of recurrent maternal infection according to restriction enzyme analysis is reactivation of latent virus, which occurs in the face of substantial maternal humoral immunity, even with intrauterine transmission of virus. Reinfection by exogenous virus remains a lesser possibility for maternal recurrences. Even more commonly, CMV can be transmitted at birth from the infected maternal genital tract and postnatally through infected breast milk, especially in highly immune populations. With the possible exception of early pneumonia, these infections appear to be innocuous."}
{"id": "PMID:233357", "title": "Perinatal infections: prevention of long-term sequelae.", "content": "All the congenital infections and most of the natal and postnatally acquired infections of man are associated with disease of the central nervous system and long-term sequelae in the survivors. The most important perinatal pathogens in this regard are group B streptococcus, Escherichia coli and other coliform bacteria, cytomegalovirus, Toxoplasma gondii and herpes simplex virus. All these agents are the subject of active and, in some instances, promising investigation. The strategies for prevention are discussed here. Recent clinical trails of two cytomegalovirus vaccines (Towne 125 and AD 169) are considered in detail.", "contents": "Perinatal infections: prevention of long-term sequelae. All the congenital infections and most of the natal and postnatally acquired infections of man are associated with disease of the central nervous system and long-term sequelae in the survivors. The most important perinatal pathogens in this regard are group B streptococcus, Escherichia coli and other coliform bacteria, cytomegalovirus, Toxoplasma gondii and herpes simplex virus. All these agents are the subject of active and, in some instances, promising investigation. The strategies for prevention are discussed here. Recent clinical trails of two cytomegalovirus vaccines (Towne 125 and AD 169) are considered in detail."}
{"id": "PMID:233361", "title": "The apparent decrease in thiotepa-induced chromosome aberrations in human lymphocytes caused by an effect of WR2721 on the cell cycle as found by the definitively determined division method.", "content": "Antimutagenic radioprotective compounds have been reported to decrease the yield of chemically induced chromosome aberrations even when administered long before the chemical mutagen thio-TEPA. Because thio-TEPA can induce aberrations in all parts of the cell cycle, it seemed likely that the apparent decrease in aberrations was the result of an effect of the antimutagen on the progression of cells through the cell cycle so that cells treated in the more sensitive stage would be scored. To test this possibility human lymphocytes were treated with the protective compound WR2721 and then thio-TEPA. The cells were grown in the presence of 5-bromodeoxyuridine, which allows the definitive determination of metaphases from cells that divided once, twice, or three times after treatment. The yield of aberrations observed in first division cells was the same whether or not the protector was present. A decrease in aberration yields appeared only in rapidly cycling cells that were in the second division at the time of fixation. Labeling experiments showed that in this rapidly dividing population fewer of the metaphase cells had been in G2 when thio-TEPA was added. The results indicate that part of the decrease in aberration yields obtained by treatment with an antimutagen several hours before the addition of a mutagen is an artifact of cell selection.", "contents": "The apparent decrease in thiotepa-induced chromosome aberrations in human lymphocytes caused by an effect of WR2721 on the cell cycle as found by the definitively determined division method. Antimutagenic radioprotective compounds have been reported to decrease the yield of chemically induced chromosome aberrations even when administered long before the chemical mutagen thio-TEPA. Because thio-TEPA can induce aberrations in all parts of the cell cycle, it seemed likely that the apparent decrease in aberrations was the result of an effect of the antimutagen on the progression of cells through the cell cycle so that cells treated in the more sensitive stage would be scored. To test this possibility human lymphocytes were treated with the protective compound WR2721 and then thio-TEPA. The cells were grown in the presence of 5-bromodeoxyuridine, which allows the definitive determination of metaphases from cells that divided once, twice, or three times after treatment. The yield of aberrations observed in first division cells was the same whether or not the protector was present. A decrease in aberration yields appeared only in rapidly cycling cells that were in the second division at the time of fixation. Labeling experiments showed that in this rapidly dividing population fewer of the metaphase cells had been in G2 when thio-TEPA was added. The results indicate that part of the decrease in aberration yields obtained by treatment with an antimutagen several hours before the addition of a mutagen is an artifact of cell selection."}
{"id": "PMID:233362", "title": "Substrate-specificity of uvr excision repair.", "content": "The substrate specificity of the uvr endonuclease, the product of the uvrA, uvrB, and uvrC genes is reviewed. It is suggested that the relatively well-defined substrate specificity of this repair enzyme is useful as a guide in determining the nature of the DNA-lesion caused by a given mutagen.", "contents": "Substrate-specificity of uvr excision repair. The substrate specificity of the uvr endonuclease, the product of the uvrA, uvrB, and uvrC genes is reviewed. It is suggested that the relatively well-defined substrate specificity of this repair enzyme is useful as a guide in determining the nature of the DNA-lesion caused by a given mutagen."}
{"id": "PMID:233363", "title": "[Research on substances with antiviral activity. X. 1-substituted-2-(methylamino) naphtho/2,1-b/furan hydrochlorides].", "content": "Some 2-(methylamino)naphtho [2,1-b] furans hydrochlorides 1-substituted were synthetized and investigates for antiviral activity in vitro against Herpes simplex virus type I (VHS-I) and parainfluenza virus type 3 HA-I/CR-8 stock.", "contents": "[Research on substances with antiviral activity. X. 1-substituted-2-(methylamino) naphtho/2,1-b/furan hydrochlorides]. Some 2-(methylamino)naphtho [2,1-b] furans hydrochlorides 1-substituted were synthetized and investigates for antiviral activity in vitro against Herpes simplex virus type I (VHS-I) and parainfluenza virus type 3 HA-I/CR-8 stock."}
{"id": "PMID:233365", "title": "Malignant fibrous histiocytoma of bone.", "content": "Eleven cases of malignant fibrous histiocytoma of bone observed during recent years are reported. An analysis is presented with regard to sex, age, site, symptoms, radiography, macroscopic and microscopic aspects. The differential diagnosis is discussed on the basis of these criteria. Because of the small number of cases and limited follow up, it was not possible to come to any definite conclusions concerning prognosis and treatment. Treatment was surgical in almost all the cases.", "contents": "Malignant fibrous histiocytoma of bone. Eleven cases of malignant fibrous histiocytoma of bone observed during recent years are reported. An analysis is presented with regard to sex, age, site, symptoms, radiography, macroscopic and microscopic aspects. The differential diagnosis is discussed on the basis of these criteria. Because of the small number of cases and limited follow up, it was not possible to come to any definite conclusions concerning prognosis and treatment. Treatment was surgical in almost all the cases."}
{"id": "PMID:233364", "title": "[Markers of hepatitis virus A and B infection in subjects undergoing a hiring examination in a large business].", "content": "The prevalence of some hepatitis-A and hepatitis-B markers has been studied in 495 individuals (male 291, female 204) attending a preemployment medical examination at a great factory in Northern Italy between November 1978 and April 1979. A 2.0% and 13.7% incidence has been respectively found for HBsAg and anti-HBs in the whole population. A statistically significative difference has been recognized between people coming from Southern and Northern Italy, as well as between first-employment subjects and workmen or countrymen. A higher incidence of anti-HBc has been detected in men, in older age groups, and Southern immigrants, without any statistically significative difference related to their previous activities. Anti-HAV antibody has been found in 57.9% of whole population, with a greater incidence in younger people and in southern immigrants. First-employment group showed a lower incidence of anti-HAV, notwithstanding the great number of southern immigrants in this group.", "contents": "[Markers of hepatitis virus A and B infection in subjects undergoing a hiring examination in a large business]. The prevalence of some hepatitis-A and hepatitis-B markers has been studied in 495 individuals (male 291, female 204) attending a preemployment medical examination at a great factory in Northern Italy between November 1978 and April 1979. A 2.0% and 13.7% incidence has been respectively found for HBsAg and anti-HBs in the whole population. A statistically significative difference has been recognized between people coming from Southern and Northern Italy, as well as between first-employment subjects and workmen or countrymen. A higher incidence of anti-HBc has been detected in men, in older age groups, and Southern immigrants, without any statistically significative difference related to their previous activities. Anti-HAV antibody has been found in 57.9% of whole population, with a greater incidence in younger people and in southern immigrants. First-employment group showed a lower incidence of anti-HAV, notwithstanding the great number of southern immigrants in this group."}
{"id": "PMID:233369", "title": "The protonation of the 5-thymyl radical in single crystals of thymine derivatives: e.s.r. and INDO evidence.", "content": "For the 5-thymyl radical, minor couplings additional to beta-protons bonded to C6 and C7 are observed in single crystals of 1-methylthymine. Hyperfine coupling tensors are given of the N3 nitrogen (+3.5/0.0/0.0 G) and of the exchangeable proton (-4.1/-2.5/-0.9 G) bonded to it. In single crystals of thymine . anhydrate, thymine . monohydrate and 5,6-dihydrothymine these additional couplings are unresolved, but are also present. INDO-calculations were performed to reproduce consistently both beta-coupling constants and additional couplings from N3 and H(N3). Comparison of experimental and calculated values to the conclusion that the 5-thymyl radical is protonated at 04 in all single crystals of thymine derivatives investigated.", "contents": "The protonation of the 5-thymyl radical in single crystals of thymine derivatives: e.s.r. and INDO evidence. For the 5-thymyl radical, minor couplings additional to beta-protons bonded to C6 and C7 are observed in single crystals of 1-methylthymine. Hyperfine coupling tensors are given of the N3 nitrogen (+3.5/0.0/0.0 G) and of the exchangeable proton (-4.1/-2.5/-0.9 G) bonded to it. In single crystals of thymine . anhydrate, thymine . monohydrate and 5,6-dihydrothymine these additional couplings are unresolved, but are also present. INDO-calculations were performed to reproduce consistently both beta-coupling constants and additional couplings from N3 and H(N3). Comparison of experimental and calculated values to the conclusion that the 5-thymyl radical is protonated at 04 in all single crystals of thymine derivatives investigated."}
{"id": "PMID:233370", "title": "Decreased repair of gamma-irradiated adenovirus in Xeroderma pigmentosum fibroblasts.", "content": "The ability of gamma-irradiated adenovirus to produce viral structural antigens (Vag) was examined in several normal and Xeroderma pigmentosum (XP) fibroblast strains. The fibroblast cultures were infected with either irradiated or nonirradiated adenovirus and at 48 hours after infection, cells were examined for the presence of Vag using immunofluorescent staining. Survival of Vag synthesis for gamma-irradiated adenovirus had a D37 value of 47 +/- 4 x 10(4) rad following the infection of seven normal fibroblast strains. The survival of this viral function was found to be significantly less following infection of the XP strains. D37 values for Vag synthesis expressed as a percentage of that obtained on normal strains were obtained for a representative strain from each of the XP complementation groups: group A, 57 per cent; group B, 61 per cent; group C, 61 per cent, group D, 59 per cent; group E, 73 per cent; and variant, 75 per cent. These results indicate that XP cells have a reduced repair capacity for some type of gamma-ray-induced DNA damage.", "contents": "Decreased repair of gamma-irradiated adenovirus in Xeroderma pigmentosum fibroblasts. The ability of gamma-irradiated adenovirus to produce viral structural antigens (Vag) was examined in several normal and Xeroderma pigmentosum (XP) fibroblast strains. The fibroblast cultures were infected with either irradiated or nonirradiated adenovirus and at 48 hours after infection, cells were examined for the presence of Vag using immunofluorescent staining. Survival of Vag synthesis for gamma-irradiated adenovirus had a D37 value of 47 +/- 4 x 10(4) rad following the infection of seven normal fibroblast strains. The survival of this viral function was found to be significantly less following infection of the XP strains. D37 values for Vag synthesis expressed as a percentage of that obtained on normal strains were obtained for a representative strain from each of the XP complementation groups: group A, 57 per cent; group B, 61 per cent; group C, 61 per cent, group D, 59 per cent; group E, 73 per cent; and variant, 75 per cent. These results indicate that XP cells have a reduced repair capacity for some type of gamma-ray-induced DNA damage."}
{"id": "PMID:233366", "title": "Converting enzyme inhibition in essential hypertension: the hypotensive response does not reflect only reduced angiotensin II formation.", "content": "To determine the relative importance of hormonal factors in mediating the hypotensive response to converting enzyme inhibition (CEI), plasma renin activity (PRA), angiotensin II, and bradykinin responses to SQ20,881 were measured in 20 supine patients with essential hypertension in balance on a 10 mEq sodium diet. Patients were divided into two groups according to their diastolic blood pressure response: responders had a decrement in diastolic pressure which exceeded 9 mm Hg, the upper value of the 95% confidence limits for normotensive patients studied under similar conditions; nonresponders did not. Compared to the nonresponders, responders not only had a higher control PRA (8.7 +/- 1.7 ng/ml/hr vs 4.8 +/- 2.1, p < 0.05) and larger decrement in plasma angiotensin II (18.7 +/- 4.9 pg/ml vs 3.2 +/- 1.7, p < 0.01), but also had a higher control bradykinin (3.2 +/- 0.7 ng/ml vs 1.1 +/- 0.2, p < 0.05) and larger increment in bradykinin (4.5 +/- 1.3 ng/ml vs 1.0 +/- 0.4, p < 0.05) following SQ20,881. Because SQ20,881 altered both angiotensin II and bradykinin concentrations, we assessed the contribution of blockade of angiotensin II formation by administering angiotensin II infusions to seven responders during coverting enzyme blockade, with the angiotensin II dose adjusted to restore diastolic pressure to control levels. The plasma angiotensin II level required to return blood pressure to control was 45 +/- 15 pg/ml higher than the control plasma angiotensin II level (p < 0.01), suggesting that some other factor(s), perhaps bradykinin, are also responsible for the hypotensive response to converting enzyme inhibition.", "contents": "Converting enzyme inhibition in essential hypertension: the hypotensive response does not reflect only reduced angiotensin II formation. To determine the relative importance of hormonal factors in mediating the hypotensive response to converting enzyme inhibition (CEI), plasma renin activity (PRA), angiotensin II, and bradykinin responses to SQ20,881 were measured in 20 supine patients with essential hypertension in balance on a 10 mEq sodium diet. Patients were divided into two groups according to their diastolic blood pressure response: responders had a decrement in diastolic pressure which exceeded 9 mm Hg, the upper value of the 95% confidence limits for normotensive patients studied under similar conditions; nonresponders did not. Compared to the nonresponders, responders not only had a higher control PRA (8.7 +/- 1.7 ng/ml/hr vs 4.8 +/- 2.1, p < 0.05) and larger decrement in plasma angiotensin II (18.7 +/- 4.9 pg/ml vs 3.2 +/- 1.7, p < 0.01), but also had a higher control bradykinin (3.2 +/- 0.7 ng/ml vs 1.1 +/- 0.2, p < 0.05) and larger increment in bradykinin (4.5 +/- 1.3 ng/ml vs 1.0 +/- 0.4, p < 0.05) following SQ20,881. Because SQ20,881 altered both angiotensin II and bradykinin concentrations, we assessed the contribution of blockade of angiotensin II formation by administering angiotensin II infusions to seven responders during coverting enzyme blockade, with the angiotensin II dose adjusted to restore diastolic pressure to control levels. The plasma angiotensin II level required to return blood pressure to control was 45 +/- 15 pg/ml higher than the control plasma angiotensin II level (p < 0.01), suggesting that some other factor(s), perhaps bradykinin, are also responsible for the hypotensive response to converting enzyme inhibition."}
{"id": "PMID:233373", "title": "Myxoid variety of malignant fibrous soft tissue histiocytoma.", "content": "Three cases of the myxoid variety of malignant fibrous histiocytoma (I.F.M.) of the soft tissues are reported. This condition should be recognised as a separate entity differing from other benign pseudosarcomatous or malignant lesions of the soft tissues in that the myxoid component is present not as an occasional background, but as an integral constituent of the neoplasm. This indicates a more favourable prognosis as compared with other varieties of malignant fibrous histiocytoma.", "contents": "Myxoid variety of malignant fibrous soft tissue histiocytoma. Three cases of the myxoid variety of malignant fibrous histiocytoma (I.F.M.) of the soft tissues are reported. This condition should be recognised as a separate entity differing from other benign pseudosarcomatous or malignant lesions of the soft tissues in that the myxoid component is present not as an occasional background, but as an integral constituent of the neoplasm. This indicates a more favourable prognosis as compared with other varieties of malignant fibrous histiocytoma."}
{"id": "PMID:233374", "title": "Sarcoma in Paget's disease (11 cases).", "content": "Eleven cases of sarcoma in Paget's disease of bone are presented, together with an extensive review of the literature. These neoplasms are rare but not exceptional, and mostly affect male subjects in the seventh decade of life. The sites most frequently affected are the pelvis, femur and humerus. In 30 per cent of cases these neoplasms are multifocal. Radiographically the lesions are nearly always osteolytic. The radiographic diagnosis may, however, be quite difficult, especially in the presence of the severe (but benign) osteolyic lesions that sometimes occur in Paget's disease. Morphologically these tumours are mostly highly polymorphic sarcomas. The cases in this series were diagnosed histologically as osteosarcoma, grade 3 fibrosarcoma, and malignant fibrous histiocytoma; but there are no prognostic differences between the various histological types. The prognosis is very serious, only about 3 per cent of patients surviving for five years from the time of diagnosis. Therapy, unfortunately nearly always palliative, is based on amputation or disarticulation after sections biopsy in cases where the disease is localised to the limbs, and on radiotherapy in cases not amenable to surgery.", "contents": "Sarcoma in Paget's disease (11 cases). Eleven cases of sarcoma in Paget's disease of bone are presented, together with an extensive review of the literature. These neoplasms are rare but not exceptional, and mostly affect male subjects in the seventh decade of life. The sites most frequently affected are the pelvis, femur and humerus. In 30 per cent of cases these neoplasms are multifocal. Radiographically the lesions are nearly always osteolytic. The radiographic diagnosis may, however, be quite difficult, especially in the presence of the severe (but benign) osteolyic lesions that sometimes occur in Paget's disease. Morphologically these tumours are mostly highly polymorphic sarcomas. The cases in this series were diagnosed histologically as osteosarcoma, grade 3 fibrosarcoma, and malignant fibrous histiocytoma; but there are no prognostic differences between the various histological types. The prognosis is very serious, only about 3 per cent of patients surviving for five years from the time of diagnosis. Therapy, unfortunately nearly always palliative, is based on amputation or disarticulation after sections biopsy in cases where the disease is localised to the limbs, and on radiotherapy in cases not amenable to surgery."}
{"id": "PMID:233376", "title": "[The metabolic effects of contraception with oestrogen-progestogen products (author's transl)].", "content": "A synthesis has been attempted to explain the metabolic action of oestrogen-progestogens: and their action on carbohydrates, triglycerides, cholesterol, lipoproteins and coagulation has been reviewed. Carbohydrate tolerance can evolve in different ways, depending on the case. On the one hand hyperglycaemia, which is provoked by taking carbohydrates by mouth in a primitively pathological way, can be improved while on the other hand there can be diminution in carbohydrate tolerance in other cases. Two factors, however, remain constant, hyperinsulinism and resistance to insulin. There is no way of predicting how carbohydrate tolerance will behave. That is why pills that contain oestrogens and progestogens, even if they are \"mini-dose\" pills, are contra-indicated for women who have pancreatic diabetes. Pills with a high oestrogen content raise the triglycerides, while those which have a higher progestogen content tend to raise the blood cholesterol levels. High-density lipoprotein tends to be raised with an oestrogenic milieu and lowered with progestogens or with pills that have a strong progestogen content.", "contents": "[The metabolic effects of contraception with oestrogen-progestogen products (author's transl)]. A synthesis has been attempted to explain the metabolic action of oestrogen-progestogens: and their action on carbohydrates, triglycerides, cholesterol, lipoproteins and coagulation has been reviewed. Carbohydrate tolerance can evolve in different ways, depending on the case. On the one hand hyperglycaemia, which is provoked by taking carbohydrates by mouth in a primitively pathological way, can be improved while on the other hand there can be diminution in carbohydrate tolerance in other cases. Two factors, however, remain constant, hyperinsulinism and resistance to insulin. There is no way of predicting how carbohydrate tolerance will behave. That is why pills that contain oestrogens and progestogens, even if they are \"mini-dose\" pills, are contra-indicated for women who have pancreatic diabetes. Pills with a high oestrogen content raise the triglycerides, while those which have a higher progestogen content tend to raise the blood cholesterol levels. High-density lipoprotein tends to be raised with an oestrogenic milieu and lowered with progestogens or with pills that have a strong progestogen content."}
{"id": "PMID:233372", "title": "Horse muscle acylphosphatase: a more rapid purification procedure and crystallization.", "content": "A crystalline acyl phosphatase has been obtained from horse muscle. The enzyme purified by a modified procedure which allowed to obtain a larger yield with respect to a method previously developped in this laboratory, was homogeneous by disc electrophoresis on polyacrylamide gel. Crystals of this enzymatic protein have been obtained by the addition of ammonium sulphate to around 52% saturation.", "contents": "Horse muscle acylphosphatase: a more rapid purification procedure and crystallization. A crystalline acyl phosphatase has been obtained from horse muscle. The enzyme purified by a modified procedure which allowed to obtain a larger yield with respect to a method previously developped in this laboratory, was homogeneous by disc electrophoresis on polyacrylamide gel. Crystals of this enzymatic protein have been obtained by the addition of ammonium sulphate to around 52% saturation."}
{"id": "PMID:233377", "title": "Life span changes in the presence of alpha-melanocyte-stimulating-hormone-containing cells in the human pituitary.", "content": "Since recent circumstantial evidence has suggested possible functions of alpha-MSH in intrauterine growth and labour, the presence of this hormone in the human pituitary was determined by means of the indirect immunofluorescence procedure during development and adulthood. Cross reaction of the antibodies with other peptides was measured after which they were purified by solid phase absorption. Experiments on the rat pituitary showed that staining of alpha-MSH- and ACTH-containing cells could be obtained well until 48 h after death. In the pars distalis the ability of ACTH-containing cells to take up stain increased during the period of post-mortem storage. In the youngest human fetus studied (15 weeks) only alpha-MSH-containing cells were found in the pars intermedia and no ACTH-containing cells were observed. In the other fetal pituitaries a distinct pars intermedia containing more alpha-MSH cells than ACTH cells was found. In the pars distalis of the fetuses more ACTH- than alpha-MSH-containing cells were observed. From birth to 19 years, progressively fewer alpha-MSH containing cells could be detected in the 'zona intermedia' and pars distalis, while in adults only a few such cells were found in either area. Irrespective of age, sex, cause of death or therapy, alpha-MSH-containing cells were found in all pituitaries throughout life. The number of ACTH containing cells gradually increased in the zona intermedia and pars distalis and reached a high adult level in the latter structure. In the pituitaries of seven anencephalics, no alpha-MSH-containing cells were present. The presence of alpha-MSH in the fetal pars intermedia, the change in the ratio of the alpha-MSH/ACTH cells during the course of development, and the absence of alpha-MSH in anencephaly all support the possibility that human fetal pituitary alpha-MSH is involved in both intrauterine growth and fetal adrenal function and thus also in parturition.", "contents": "Life span changes in the presence of alpha-melanocyte-stimulating-hormone-containing cells in the human pituitary. Since recent circumstantial evidence has suggested possible functions of alpha-MSH in intrauterine growth and labour, the presence of this hormone in the human pituitary was determined by means of the indirect immunofluorescence procedure during development and adulthood. Cross reaction of the antibodies with other peptides was measured after which they were purified by solid phase absorption. Experiments on the rat pituitary showed that staining of alpha-MSH- and ACTH-containing cells could be obtained well until 48 h after death. In the pars distalis the ability of ACTH-containing cells to take up stain increased during the period of post-mortem storage. In the youngest human fetus studied (15 weeks) only alpha-MSH-containing cells were found in the pars intermedia and no ACTH-containing cells were observed. In the other fetal pituitaries a distinct pars intermedia containing more alpha-MSH cells than ACTH cells was found. In the pars distalis of the fetuses more ACTH- than alpha-MSH-containing cells were observed. From birth to 19 years, progressively fewer alpha-MSH containing cells could be detected in the 'zona intermedia' and pars distalis, while in adults only a few such cells were found in either area. Irrespective of age, sex, cause of death or therapy, alpha-MSH-containing cells were found in all pituitaries throughout life. The number of ACTH containing cells gradually increased in the zona intermedia and pars distalis and reached a high adult level in the latter structure. In the pituitaries of seven anencephalics, no alpha-MSH-containing cells were present. The presence of alpha-MSH in the fetal pars intermedia, the change in the ratio of the alpha-MSH/ACTH cells during the course of development, and the absence of alpha-MSH in anencephaly all support the possibility that human fetal pituitary alpha-MSH is involved in both intrauterine growth and fetal adrenal function and thus also in parturition."}
{"id": "PMID:233379", "title": "[Primary malignant tumour of the liver associated with the ingestion of oral contraceptives (author's transl)].", "content": "A 42-year-old woman, who had been taking oral contraceptives for 10 years, developed a primary carcinoma of the liver. The diagnosis was made by biopsy under laparoscopic control. Twenty one cases have already been reported in the literature. The aetiological role of contraceptives in the development of generally benign (approximately 200 published cases) and sometime malignant hepatic lesions, has not been definitely proven. The regression of certain benign tumours when contraceptives are stopped is the essential argument. In some patients, the association of benign lesions and of hepatic carcinoma suggests a single pathogenesis. The early recognition of such lesions justifies their being sought routinely in patients taking oral contraceptives (palpation of the liver, questioning concerning pain in the hepatic region). A national register will be required in order to determine their exact prevalence.", "contents": "[Primary malignant tumour of the liver associated with the ingestion of oral contraceptives (author's transl)]. A 42-year-old woman, who had been taking oral contraceptives for 10 years, developed a primary carcinoma of the liver. The diagnosis was made by biopsy under laparoscopic control. Twenty one cases have already been reported in the literature. The aetiological role of contraceptives in the development of generally benign (approximately 200 published cases) and sometime malignant hepatic lesions, has not been definitely proven. The regression of certain benign tumours when contraceptives are stopped is the essential argument. In some patients, the association of benign lesions and of hepatic carcinoma suggests a single pathogenesis. The early recognition of such lesions justifies their being sought routinely in patients taking oral contraceptives (palpation of the liver, questioning concerning pain in the hepatic region). A national register will be required in order to determine their exact prevalence."}
{"id": "PMID:233390", "title": "[Determination of umbilical cord blood Ig and its correlation with prenatal infections (author's transl)].", "content": "IgG, IgM and IgA were measured in 120 funicular blood samples. At the same time, these determinations were assayed in the mothers. In the serum samples of the newborn, IgA and IgM were found to have levels over 20 mg/100 ml. Antibodies against rubella virus, cytomegalus virus, Listeria monocytogenes and Toxoplasma gondii were measured in order to investigate a possible intrauterine infection. All Ig determinations were performed through the radial immunodiffusion method.", "contents": "[Determination of umbilical cord blood Ig and its correlation with prenatal infections (author's transl)]. IgG, IgM and IgA were measured in 120 funicular blood samples. At the same time, these determinations were assayed in the mothers. In the serum samples of the newborn, IgA and IgM were found to have levels over 20 mg/100 ml. Antibodies against rubella virus, cytomegalus virus, Listeria monocytogenes and Toxoplasma gondii were measured in order to investigate a possible intrauterine infection. All Ig determinations were performed through the radial immunodiffusion method."}
{"id": "PMID:233395", "title": "Comparison of suture materials for intestinal anastomosis.", "content": "Ninety end-to-end entero-anastomoses were prepared in 45 dogs by inverted single row knotted sutures. Half of the anastomoses were carried out on the small intestine, the other half on the colon. Of the two non-absorbable materials that of the polyester type proved to be the best. Of the absorbable materials Dexon can be recommended for intestinal anastomoses, but on the colon Dexon is not reliable. Plain catgut is not recommended for this kind of anastomoses.", "contents": "Comparison of suture materials for intestinal anastomosis. Ninety end-to-end entero-anastomoses were prepared in 45 dogs by inverted single row knotted sutures. Half of the anastomoses were carried out on the small intestine, the other half on the colon. Of the two non-absorbable materials that of the polyester type proved to be the best. Of the absorbable materials Dexon can be recommended for intestinal anastomoses, but on the colon Dexon is not reliable. Plain catgut is not recommended for this kind of anastomoses."}
{"id": "PMID:233396", "title": "[Blood coagulation disorder in islet cell adenoma].", "content": "Coagulation physiologic tests were carried out and plasminogen activity and concentration were measured in the case of 6 patients (5 islet cell adenomas and 1 islet cell carcinoma). Except a reduced plasminogen activity in the postoperative phase no other unequivocally pathologic data were found. This phenomenon can probably by attributed to the enhanced plasmin inhibitors of the human plasma. The problem of so-called hypercoagulaemia of these patients can be clarified only after the investigation of the half-lives of the various coagulation factors.", "contents": "[Blood coagulation disorder in islet cell adenoma]. Coagulation physiologic tests were carried out and plasminogen activity and concentration were measured in the case of 6 patients (5 islet cell adenomas and 1 islet cell carcinoma). Except a reduced plasminogen activity in the postoperative phase no other unequivocally pathologic data were found. This phenomenon can probably by attributed to the enhanced plasmin inhibitors of the human plasma. The problem of so-called hypercoagulaemia of these patients can be clarified only after the investigation of the half-lives of the various coagulation factors."}
{"id": "PMID:233400", "title": "Effect of ACTH-stimulated glucocorticoid hypersecretion on the serum concentrations of thyroxine-binding globulin, thyroxine, triiodothyronine, reverse triiodothyronine and on the TSH-response to TRH.", "content": "The responses of serum concentrations of TSH, thyroxine (T4), triiodothyronine (T3) and of reverse triiodothyronine (rT3) to i. v. administration of 0.4 mg THR were examined prior to (and after) i. m. administration of ACTH (2 mg Synacthen Depot) in 7 euthyroid women using estrogen-containing oral contraceptives and in 8 controls, with the following results: (1) an increase in endogenous glucocorticoid secretion is associated with a depression of the TSH response to TRH; (2) TSH formed in decreased amounts is still capable of stimulating thyroid secretion; (3) the increased serum corticoid levels fail to affect the secretory response of the thyroid to TSH; (4) control of the pituitary-thyroid axis remains normal in the presence of increased serum thyroxine-binding globulin (TBG) levels. In a further series the serum levels of TBG, T4, T3, rT3 and cortisol under the effect of ACTH-induced endogenous glucocorticoid hypersecretion were studied in 6 normal untreated controls, in 6 normal women using oral contraceptives and in 10 untreated hyperthyroid patients. During four days subsequent to treatment the serum TBG levels decreased, maximum decrease being found in the users of oral contraceptives, minimum decrease in the controls. Serum T4 was found to decrease during 2 to 4 days, serum T3 parallel with an increase in serum rT3, for 1 to 2 days, subsequent for ACTH loading. In the euthyroid cases also the serum TSH levels showed a transitory decline. It is concluded that in case of endogenous hyperproduction of glucocorticoids (1) T4 leads to T3 monodeiodination decreases and T4 leads to rT3 conversion increases parallel with the changes in the serum cortisol levels; (2) TBG synthesis is inhibited by endogenous glucocorticoids; (3) the changes in serum TBG levels are accompanied by a decrease in the serum T4 concentrations.", "contents": "Effect of ACTH-stimulated glucocorticoid hypersecretion on the serum concentrations of thyroxine-binding globulin, thyroxine, triiodothyronine, reverse triiodothyronine and on the TSH-response to TRH. The responses of serum concentrations of TSH, thyroxine (T4), triiodothyronine (T3) and of reverse triiodothyronine (rT3) to i. v. administration of 0.4 mg THR were examined prior to (and after) i. m. administration of ACTH (2 mg Synacthen Depot) in 7 euthyroid women using estrogen-containing oral contraceptives and in 8 controls, with the following results: (1) an increase in endogenous glucocorticoid secretion is associated with a depression of the TSH response to TRH; (2) TSH formed in decreased amounts is still capable of stimulating thyroid secretion; (3) the increased serum corticoid levels fail to affect the secretory response of the thyroid to TSH; (4) control of the pituitary-thyroid axis remains normal in the presence of increased serum thyroxine-binding globulin (TBG) levels. In a further series the serum levels of TBG, T4, T3, rT3 and cortisol under the effect of ACTH-induced endogenous glucocorticoid hypersecretion were studied in 6 normal untreated controls, in 6 normal women using oral contraceptives and in 10 untreated hyperthyroid patients. During four days subsequent to treatment the serum TBG levels decreased, maximum decrease being found in the users of oral contraceptives, minimum decrease in the controls. Serum T4 was found to decrease during 2 to 4 days, serum T3 parallel with an increase in serum rT3, for 1 to 2 days, subsequent for ACTH loading. In the euthyroid cases also the serum TSH levels showed a transitory decline. It is concluded that in case of endogenous hyperproduction of glucocorticoids (1) T4 leads to T3 monodeiodination decreases and T4 leads to rT3 conversion increases parallel with the changes in the serum cortisol levels; (2) TBG synthesis is inhibited by endogenous glucocorticoids; (3) the changes in serum TBG levels are accompanied by a decrease in the serum T4 concentrations."}
{"id": "PMID:233401", "title": "The role of the ATP--adenylate cyclase--cAMP system and its pharmacological regulation in the development of gastric hypersecretion and ulceration.", "content": "The role and pharmacological regulation of the ATP-adenylate-cyclase--cAMP system were studied in the mucosa of the gastric fundus, and in the forestomach, of pylorus-ligated rats to elucidate the development of gastric hypersecretion and ulceration. (1) cAMP content of the tissue of the fundus mucosa and of the forestomach decreased before the significant increase of gastric H+ output and ulcer development; (2) the gastric H+ outputs depended on the breakdown of ATP in the fundus mucosa; (3) the gastric H+ secretion was inhibited in a dose-dependent way by theophylline, epinephrine and cimetidine; (4) the inhibition of gastric H+ secretion by epinephrine , theophylline or epinephrine plus theophylline associated with a significant increase in the mucosal cAMP of the gastric fundus (5) the significant increase in gastric H+ secretion due to histamine associated with a significant decrease in fundic mucosal cAMP; (6) the gastric H+ secretion could be inhibited dose-dependently by ADP, AMP, cyclic 2', 3'-AMP and cAMP; (7) the inhibition of gastric H+ secretion by cimetidine developed without and with histamine application in pylorus-ligated rats; (8) the histamine on gastric H+ secretion could not be stimulated further with theophylline (9) no significant correlation was found between the mucosal cAMP level and the gastric H+ secretion and/or between the decrease of mucosal cAMP content and gastric H+ secretion. It has been concluded that in pylorus-ligated rats (1) the gastric H+ secretion is an ATP-dependent process; (2) the cAMP system has an inhibitory effect as regards the development of gastric hypersecretion and of ulceration; (3) histamine and cimetidine show no close correlation with the cAMP system; (4) an extracellular and intracellular feed-back mechanism system exists between th ATP-membrane-bound ATPase-ADP and the ATP--adenylate cyclase--cAMP systems in the background of the development of gastric hypersecretion and ulceration.", "contents": "The role of the ATP--adenylate cyclase--cAMP system and its pharmacological regulation in the development of gastric hypersecretion and ulceration. The role and pharmacological regulation of the ATP-adenylate-cyclase--cAMP system were studied in the mucosa of the gastric fundus, and in the forestomach, of pylorus-ligated rats to elucidate the development of gastric hypersecretion and ulceration. (1) cAMP content of the tissue of the fundus mucosa and of the forestomach decreased before the significant increase of gastric H+ output and ulcer development; (2) the gastric H+ outputs depended on the breakdown of ATP in the fundus mucosa; (3) the gastric H+ secretion was inhibited in a dose-dependent way by theophylline, epinephrine and cimetidine; (4) the inhibition of gastric H+ secretion by epinephrine , theophylline or epinephrine plus theophylline associated with a significant increase in the mucosal cAMP of the gastric fundus (5) the significant increase in gastric H+ secretion due to histamine associated with a significant decrease in fundic mucosal cAMP; (6) the gastric H+ secretion could be inhibited dose-dependently by ADP, AMP, cyclic 2', 3'-AMP and cAMP; (7) the inhibition of gastric H+ secretion by cimetidine developed without and with histamine application in pylorus-ligated rats; (8) the histamine on gastric H+ secretion could not be stimulated further with theophylline (9) no significant correlation was found between the mucosal cAMP level and the gastric H+ secretion and/or between the decrease of mucosal cAMP content and gastric H+ secretion. It has been concluded that in pylorus-ligated rats (1) the gastric H+ secretion is an ATP-dependent process; (2) the cAMP system has an inhibitory effect as regards the development of gastric hypersecretion and of ulceration; (3) histamine and cimetidine show no close correlation with the cAMP system; (4) an extracellular and intracellular feed-back mechanism system exists between th ATP-membrane-bound ATPase-ADP and the ATP--adenylate cyclase--cAMP systems in the background of the development of gastric hypersecretion and ulceration."}
{"id": "PMID:233402", "title": "A comparative molecular--pharmacological study of drugs inhibiting Na+--K+-dependent ATPase separated from human gastric fundic mucosa. (One receptor system and more drugs).", "content": "The inhibitory effects of atropine, epinephrine, cyclic 3', 5'-AMP (cAMP), the prostaglandins E1 (PGE1) and E2 (PGE2) pentagastrin, histamine and ouabain have been studied on the activity of Na+--K+-dependent ATPase obtained from human gastric fundic mucosa. This study compares the sensitivity of the enzyme to a variety of drugs, applying the law of one receptor and more drugs. It was found that (1) the doses of drugs necessary to produce 50% inhibition to Na+--K+-dependent ATPase activity (affinity, pD2 value) significantly differ from each other C (atropine, 9.50; epinephrine, 8.60; cAMP: 11.30; PGE1, 9.30; PGE2, 9.45; pentagastrin, 9.45; histamine, 9.70 and ouabain, 9.50); (2) the intrinsic activities of drugs to Na+--K+-dependent, ATPase in comparison with ouabain (alpha=1.00) differ: atropine, PGE1, PGE2 and histamine, 1.00; pentagastrin, 0.87; cAMP, 0.48 and epinephrine, 0.41; (3) the inhibitory effects of different drugs, on Na+--K+-dependent ATPase system, depend on the magnitude of enzyme activity from human gastric fundic mucosa. It has been concluded that (1) the sensitivity of these drugs to the Na+--K+-dependent ATPase system and to the adenylate cyclase system, both obtained from human gastric mucosa, significantly differs from each other; (2) the main effect of pentagastrin and histamine on human gastric secretory function differs from the function of Na+--K+-dependent ATPase system; (3) the role of Na+--K+-dependent ATPase system and of adenylate cyclase can be separated pharmacologically from the point of view of human gastric H+ secretion.", "contents": "A comparative molecular--pharmacological study of drugs inhibiting Na+--K+-dependent ATPase separated from human gastric fundic mucosa. (One receptor system and more drugs). The inhibitory effects of atropine, epinephrine, cyclic 3', 5'-AMP (cAMP), the prostaglandins E1 (PGE1) and E2 (PGE2) pentagastrin, histamine and ouabain have been studied on the activity of Na+--K+-dependent ATPase obtained from human gastric fundic mucosa. This study compares the sensitivity of the enzyme to a variety of drugs, applying the law of one receptor and more drugs. It was found that (1) the doses of drugs necessary to produce 50% inhibition to Na+--K+-dependent ATPase activity (affinity, pD2 value) significantly differ from each other C (atropine, 9.50; epinephrine, 8.60; cAMP: 11.30; PGE1, 9.30; PGE2, 9.45; pentagastrin, 9.45; histamine, 9.70 and ouabain, 9.50); (2) the intrinsic activities of drugs to Na+--K+-dependent, ATPase in comparison with ouabain (alpha=1.00) differ: atropine, PGE1, PGE2 and histamine, 1.00; pentagastrin, 0.87; cAMP, 0.48 and epinephrine, 0.41; (3) the inhibitory effects of different drugs, on Na+--K+-dependent ATPase system, depend on the magnitude of enzyme activity from human gastric fundic mucosa. It has been concluded that (1) the sensitivity of these drugs to the Na+--K+-dependent ATPase system and to the adenylate cyclase system, both obtained from human gastric mucosa, significantly differs from each other; (2) the main effect of pentagastrin and histamine on human gastric secretory function differs from the function of Na+--K+-dependent ATPase system; (3) the role of Na+--K+-dependent ATPase system and of adenylate cyclase can be separated pharmacologically from the point of view of human gastric H+ secretion."}
{"id": "PMID:233403", "title": "In vivo and in vitro effects of LH-RH on cAMP content of anterior pituitary in rats.", "content": "Changes in the cAMP content of anterior pituitary of male rats were studied after in vivo administration of LH-RH or in vitro incubation in the presence of LH-RH. Although a significant rise was observed 5 min after in vivo injection of LH-RH, the cAMP level increased after only a two-hour lag period in vitro. Maximum level was reached in vivo with 1 microgram LH-RH/100 g b.w., but there was no maximal production in vitro even in the presence of 5 x 10(-6) M LH-RH. A summary of the available observations on the effect of LH-RH on pituitary cAMP level is given in the present paper.", "contents": "In vivo and in vitro effects of LH-RH on cAMP content of anterior pituitary in rats. Changes in the cAMP content of anterior pituitary of male rats were studied after in vivo administration of LH-RH or in vitro incubation in the presence of LH-RH. Although a significant rise was observed 5 min after in vivo injection of LH-RH, the cAMP level increased after only a two-hour lag period in vitro. Maximum level was reached in vivo with 1 microgram LH-RH/100 g b.w., but there was no maximal production in vitro even in the presence of 5 x 10(-6) M LH-RH. A summary of the available observations on the effect of LH-RH on pituitary cAMP level is given in the present paper."}
{"id": "PMID:233404", "title": "Central and peripheral adrenergic mechanisms in endotoxin fever and newborn guinea pigs.", "content": "In 0--3 day-old guinea pigs cerebroventricular pretreatment with alpha-methyl-p-tyrosine failed to modify the course of fever induced by E. coli endotoxin administration into the cerebral ventricles. Central or intraperitoneal administration of phentolamine or central administration of propranolol were also ineffective. Intraperitoneal propranolol, however, prevented both the first and the second temperature rise after endotoxin, while the transient fall in temperature that usually occurs between them still ensued. Central noradrenergic mechanisms seem to play, at most, a minor role in the mediation of endotoxin fever, while the integrity of peripheral beta adrenergic receptors is indispensable for the febrile response to occur.", "contents": "Central and peripheral adrenergic mechanisms in endotoxin fever and newborn guinea pigs. In 0--3 day-old guinea pigs cerebroventricular pretreatment with alpha-methyl-p-tyrosine failed to modify the course of fever induced by E. coli endotoxin administration into the cerebral ventricles. Central or intraperitoneal administration of phentolamine or central administration of propranolol were also ineffective. Intraperitoneal propranolol, however, prevented both the first and the second temperature rise after endotoxin, while the transient fall in temperature that usually occurs between them still ensued. Central noradrenergic mechanisms seem to play, at most, a minor role in the mediation of endotoxin fever, while the integrity of peripheral beta adrenergic receptors is indispensable for the febrile response to occur."}
{"id": "PMID:233405", "title": "The role of beta receptors in the regulation of renin release.", "content": "The effect of the primarily beta 2 type adrenergic receptor stimulating terbutaline (10(-7)--10(-5) M) and of the beta 1 and beta 2 type adrenergic receptor stimulating isoproterenol (10(-7)--10(-5) M) was studied on renin release from incubated slices of renal cortex. Renin release and cAMP content of the slices were significantly higher in the presence of both terbutaline and isoproterenol. A logarithmic dose--response relationship was shown to be present between the beta mimetics and the renin concentration in the medium, and the cAMP content of tissue slices. In equal doses isoproterenol was about 1.5 times more potent than terbutaline. No change was seen in the renin content of the tissue slices. The results supports the view that beside the beta 1 type adrenergic receptors of the renal cortex--even if to a lesser extent--the beta 2 type adrenergic receptors, too, are involved in the regulation of renin release.", "contents": "The role of beta receptors in the regulation of renin release. The effect of the primarily beta 2 type adrenergic receptor stimulating terbutaline (10(-7)--10(-5) M) and of the beta 1 and beta 2 type adrenergic receptor stimulating isoproterenol (10(-7)--10(-5) M) was studied on renin release from incubated slices of renal cortex. Renin release and cAMP content of the slices were significantly higher in the presence of both terbutaline and isoproterenol. A logarithmic dose--response relationship was shown to be present between the beta mimetics and the renin concentration in the medium, and the cAMP content of tissue slices. In equal doses isoproterenol was about 1.5 times more potent than terbutaline. No change was seen in the renin content of the tissue slices. The results supports the view that beside the beta 1 type adrenergic receptors of the renal cortex--even if to a lesser extent--the beta 2 type adrenergic receptors, too, are involved in the regulation of renin release."}
{"id": "PMID:233406", "title": "Vitamin C, high density lipoproteins and heart disease in elderly subjects.", "content": "Plasma vitamin C, total and high density lipoprotein (HDL) cholesterol and cortisol levels were measured in a random sample of 337 elderly subjects living at home in S. Wales; measurements of relative body weight and information about fruit intake, smoking habits and symptoms of cardiovascular disease were also collected. There was a sex difference, over all age groups, in plasma vitamin C and in total HDL cholesterol levels. Plasma vitamin C was strongly correlated with fruit intake in both sexes. Both HDL cholesterol and low and very density lipoprotein (LDL + VLDL) cholesterol levels tended to increase with increasing plasma vitamin C but this reached significance only for the LDL + VLDL fraction. In addition, HDL cholesterol was negatively correlated with Quetelet's index in the women. Symptoms and medication for heart disease did not correlate significantly with plasma vitamin C or with HDL cholesterol levels, but reported angina showed a weak positive association with total cholesterol in the men, and there was some evidence of increased cortisol levels in subjects with heart disease.", "contents": "Vitamin C, high density lipoproteins and heart disease in elderly subjects. Plasma vitamin C, total and high density lipoprotein (HDL) cholesterol and cortisol levels were measured in a random sample of 337 elderly subjects living at home in S. Wales; measurements of relative body weight and information about fruit intake, smoking habits and symptoms of cardiovascular disease were also collected. There was a sex difference, over all age groups, in plasma vitamin C and in total HDL cholesterol levels. Plasma vitamin C was strongly correlated with fruit intake in both sexes. Both HDL cholesterol and low and very density lipoprotein (LDL + VLDL) cholesterol levels tended to increase with increasing plasma vitamin C but this reached significance only for the LDL + VLDL fraction. In addition, HDL cholesterol was negatively correlated with Quetelet's index in the women. Symptoms and medication for heart disease did not correlate significantly with plasma vitamin C or with HDL cholesterol levels, but reported angina showed a weak positive association with total cholesterol in the men, and there was some evidence of increased cortisol levels in subjects with heart disease."}
{"id": "PMID:233408", "title": "Glomus tumors of the temporal region: surgical therapy.", "content": "A series of 23 patients with glomus tumors of the temporal region, treated surgically at the ENT Department, University of Zurich, Switzerland from 1970 to 1977, is presented. A system of classification as to tumor size is described with tympanic, tympanomastoid, infralabyrinthine and intracranial tumors categorized as types A, B, C, and D respectively. A majority of tumors, 12 of 19 were infralabyrinthine (type C), and a surgical approach featuring permanent anterior displacement of the facial nerve, an cavity obliteration, has been employed with the aim of total tumor extirpation. There were five males in this series, with a mean age 22 years younger than for the females and all having infralabyrinthine (type C) tumors. The most frequent clinical presentation included pulsatile tinnitus, hearing loss, and observable tumor mass in the ear. Fifteen of 23 patients had significant hearing loss, of varying types on the tumor side, with one presenting as sudden hearing loss, and another as progressive unilateral sensorineural loss over several years, in the absence, initially, of tinnitus. Ten of 23 patients with type B, C, and D tumors had cranial nerve involvement, seven and tenth being the most frequent. Because of slow growth and tendency to multicentric origin, final conclusions cannot be made regarding treatment in such a recent series of cases. However, the impression gained suggests that radiotherapy is less effective than complete surgical excision, and that partial excision is to be avoided.", "contents": "Glomus tumors of the temporal region: surgical therapy. A series of 23 patients with glomus tumors of the temporal region, treated surgically at the ENT Department, University of Zurich, Switzerland from 1970 to 1977, is presented. A system of classification as to tumor size is described with tympanic, tympanomastoid, infralabyrinthine and intracranial tumors categorized as types A, B, C, and D respectively. A majority of tumors, 12 of 19 were infralabyrinthine (type C), and a surgical approach featuring permanent anterior displacement of the facial nerve, an cavity obliteration, has been employed with the aim of total tumor extirpation. There were five males in this series, with a mean age 22 years younger than for the females and all having infralabyrinthine (type C) tumors. The most frequent clinical presentation included pulsatile tinnitus, hearing loss, and observable tumor mass in the ear. Fifteen of 23 patients had significant hearing loss, of varying types on the tumor side, with one presenting as sudden hearing loss, and another as progressive unilateral sensorineural loss over several years, in the absence, initially, of tinnitus. Ten of 23 patients with type B, C, and D tumors had cranial nerve involvement, seven and tenth being the most frequent. Because of slow growth and tendency to multicentric origin, final conclusions cannot be made regarding treatment in such a recent series of cases. However, the impression gained suggests that radiotherapy is less effective than complete surgical excision, and that partial excision is to be avoided."}
{"id": "PMID:233409", "title": "Glomus jugulare tumors with intracranial extension.", "content": "A glomus jugulare tumor with posterior fossa extension needs the expertise of the neuro-otologic surgeon and neurosurgeon to obtain total tumor removal. A one-stage combined otologic and neurosurgical procedure is presented for removal of base of skull tumors posterior to the carotid artery. Twelve cases of this type of tumor have been seen at The Cleveland Clinic. Two cases are presented in detail to illustrate the applicability of this procedure. In cases with infection around the temporal portion of the tumor, tumor extension around or anterior to the carotid artery, or extensive involvement of the posterior fossa, the procedure should be performed in two stages.", "contents": "Glomus jugulare tumors with intracranial extension. A glomus jugulare tumor with posterior fossa extension needs the expertise of the neuro-otologic surgeon and neurosurgeon to obtain total tumor removal. A one-stage combined otologic and neurosurgical procedure is presented for removal of base of skull tumors posterior to the carotid artery. Twelve cases of this type of tumor have been seen at The Cleveland Clinic. Two cases are presented in detail to illustrate the applicability of this procedure. In cases with infection around the temporal portion of the tumor, tumor extension around or anterior to the carotid artery, or extensive involvement of the posterior fossa, the procedure should be performed in two stages."}
{"id": "PMID:233411", "title": "Seizures and related epileptiform activity in hippocampus transplanted to the anterior chamber of the eye: modulation by cholinergic and adrenergic input.", "content": "Transplants of rat hippocampus into the anterior chamber of the eye of a host animal were used to assess the effects of cholinergic and adrenergic neuronal inputs on the generation and duration of seizure activity. Cholinomimetics initiated both seizures and hypersynchronous neuronal activity in the transplants. Cyclic guanosine monophosphate (GMP) derivatives and isobutyl methylxanthine elicited similar changes. Reflex activation of the cholinergic parasympathetic input to the iris and transplant by illumination of the ipsilateral retina also induced seizures or increased the rate of penicillin-induced interictal spike discharge. Application of beta-adrenergic agonists inhibited interictal spikes and paroxysmal depolarizing shifts induced by penicillin. Fluorescence histochemical studies showed that host sympathetic adrenergic fibers derived from the ground plexus of the iris invaded the transplant to form fine varicose nerve terminals. Activation of these adrenergic afferents to the transplant diminished both the amplitude and frequency of penicillin-induced epileptiform activity. Epileptiform activity in hippocampal occular transplants is strongly modulated by cholinergic and adrenergic neuronal inputs, with the former exerting a facilatory influence and the latter, an inhibitory effect.", "contents": "Seizures and related epileptiform activity in hippocampus transplanted to the anterior chamber of the eye: modulation by cholinergic and adrenergic input. Transplants of rat hippocampus into the anterior chamber of the eye of a host animal were used to assess the effects of cholinergic and adrenergic neuronal inputs on the generation and duration of seizure activity. Cholinomimetics initiated both seizures and hypersynchronous neuronal activity in the transplants. Cyclic guanosine monophosphate (GMP) derivatives and isobutyl methylxanthine elicited similar changes. Reflex activation of the cholinergic parasympathetic input to the iris and transplant by illumination of the ipsilateral retina also induced seizures or increased the rate of penicillin-induced interictal spike discharge. Application of beta-adrenergic agonists inhibited interictal spikes and paroxysmal depolarizing shifts induced by penicillin. Fluorescence histochemical studies showed that host sympathetic adrenergic fibers derived from the ground plexus of the iris invaded the transplant to form fine varicose nerve terminals. Activation of these adrenergic afferents to the transplant diminished both the amplitude and frequency of penicillin-induced epileptiform activity. Epileptiform activity in hippocampal occular transplants is strongly modulated by cholinergic and adrenergic neuronal inputs, with the former exerting a facilatory influence and the latter, an inhibitory effect."}
{"id": "PMID:233412", "title": "Effects of reserpine, propranolol, and aminophylline on seizure activity and CNS cyclic nucleotides.", "content": "Convulsant doses of pentylenetetrazol (100 mg/kg) increase levels of both cyclic adenosine monophosphate (AMP) and cyclic guanosine monophosphate (GMP in mouse cerebral cortex and hippocampus. In animals pretreated with reserpine, propranolol, or aminophylline, pentylenetetrazol seizures were more severe, cyclic AMP elevations were attenuated or blocked, and cyclic GMP increases were unaffected or augmented. These data indicate that norepinephrine, adenosine, and perhaps other biogenic amines have a regulatory effect on cyclic AMP, but not cyclic GMP, levels in epileptic brain. An increased level of cyclic AMP in brain tissue may have an antiepileptic effect leading to seizure attenuation or termination. By contrast, elevated levels of cyclic GMP may have an epileptogenic effect in initiating or maintaining seizure activity.", "contents": "Effects of reserpine, propranolol, and aminophylline on seizure activity and CNS cyclic nucleotides. Convulsant doses of pentylenetetrazol (100 mg/kg) increase levels of both cyclic adenosine monophosphate (AMP) and cyclic guanosine monophosphate (GMP in mouse cerebral cortex and hippocampus. In animals pretreated with reserpine, propranolol, or aminophylline, pentylenetetrazol seizures were more severe, cyclic AMP elevations were attenuated or blocked, and cyclic GMP increases were unaffected or augmented. These data indicate that norepinephrine, adenosine, and perhaps other biogenic amines have a regulatory effect on cyclic AMP, but not cyclic GMP, levels in epileptic brain. An increased level of cyclic AMP in brain tissue may have an antiepileptic effect leading to seizure attenuation or termination. By contrast, elevated levels of cyclic GMP may have an epileptogenic effect in initiating or maintaining seizure activity."}
{"id": "PMID:233413", "title": "Acute generalized polyneuropathy accompanying lithium poisoning.", "content": "A woman with typical symptoms of lithium toxicity had, in addition, severe generalized sensorimotor peripheral neuropathy, which cleared completely as the recovered. Electrodiagnostic studies suggested axonal lesions; autopsy ten months later revealed no residual abnormalities. Previous studies have shown that lithium can affect peripheral nerve function, but this is the first reported case of peripheral neuropathy in association with lithium toxicity.", "contents": "Acute generalized polyneuropathy accompanying lithium poisoning. A woman with typical symptoms of lithium toxicity had, in addition, severe generalized sensorimotor peripheral neuropathy, which cleared completely as the recovered. Electrodiagnostic studies suggested axonal lesions; autopsy ten months later revealed no residual abnormalities. Previous studies have shown that lithium can affect peripheral nerve function, but this is the first reported case of peripheral neuropathy in association with lithium toxicity."}
{"id": "PMID:233414", "title": "The ultrastructure of Spirulina platensis in relation to temperature and light intensity.", "content": "The ultrastructure of Spirulina platensis, a cyanobacterium with a helical morphology, has been studied in relation to temperature and light intensity. An increase in temperature gives rise to a more tightly coiled trichome, an increase in sheath material formation and a decrease in cyanophycin (above 17 degrees C) and polyglucan (above 20 degrees C) granule concentration. An increase in light intensity leads to an increase in gas vesicle concentration while the phycobilisome content decreases. Furthermore, cylindrica bodies have been observed with a somewhat different ultrastructure from those found in other species of cyanobacteria. The occurrence, size and ultrastructure of polyhedral bodies, photosynthetic lamellae, mesosomes, lipid deposits and an unknown kidney-shaped inclusion in relation to temperature and light intensity are described.", "contents": "The ultrastructure of Spirulina platensis in relation to temperature and light intensity. The ultrastructure of Spirulina platensis, a cyanobacterium with a helical morphology, has been studied in relation to temperature and light intensity. An increase in temperature gives rise to a more tightly coiled trichome, an increase in sheath material formation and a decrease in cyanophycin (above 17 degrees C) and polyglucan (above 20 degrees C) granule concentration. An increase in light intensity leads to an increase in gas vesicle concentration while the phycobilisome content decreases. Furthermore, cylindrica bodies have been observed with a somewhat different ultrastructure from those found in other species of cyanobacteria. The occurrence, size and ultrastructure of polyhedral bodies, photosynthetic lamellae, mesosomes, lipid deposits and an unknown kidney-shaped inclusion in relation to temperature and light intensity are described."}
{"id": "PMID:233418", "title": "Persistence in humans of antibody after immunization with four alphavirus vaccines.", "content": "Immunization with attenuated VEE virus vaccine resulted in persistence of neutralizing antibody for 12 years. Immunization with inactivated WEE vaccine converted 83% of the subjects, killed EEE vaccine converted 27% and killed Chikungunya vaccine induced no significant titers. Antibody formed as a result of immunization with inactivated vaccines was of short duration, i.e. less than 1 year. Attenuated VEE was responsible for some heterologous antibody rises to the other three alphaviruses. Among the inactivated vaccines WEE and Chikungunya vaccines produced one heterologous rise each to EEE virus.", "contents": "Persistence in humans of antibody after immunization with four alphavirus vaccines. Immunization with attenuated VEE virus vaccine resulted in persistence of neutralizing antibody for 12 years. Immunization with inactivated WEE vaccine converted 83% of the subjects, killed EEE vaccine converted 27% and killed Chikungunya vaccine induced no significant titers. Antibody formed as a result of immunization with inactivated vaccines was of short duration, i.e. less than 1 year. Attenuated VEE was responsible for some heterologous antibody rises to the other three alphaviruses. Among the inactivated vaccines WEE and Chikungunya vaccines produced one heterologous rise each to EEE virus."}
{"id": "PMID:233415", "title": "[Serological survey for virus and Mycoplasma infections (author's transl)].", "content": "The Authors describe the two years follow up of complement fixing antibodies vs 4 viral antigens (Herpes simplex, Herpes zoster, Cytomegalovirus, respiratory syncytial virus, Mycoplasma pneumoniae). They evaluate the seasonal trend and the eventual clinical correlations on 3267 sera and 254 spinal fluids from hospitalized patients.", "contents": "[Serological survey for virus and Mycoplasma infections (author's transl)]. The Authors describe the two years follow up of complement fixing antibodies vs 4 viral antigens (Herpes simplex, Herpes zoster, Cytomegalovirus, respiratory syncytial virus, Mycoplasma pneumoniae). They evaluate the seasonal trend and the eventual clinical correlations on 3267 sera and 254 spinal fluids from hospitalized patients."}
{"id": "PMID:233420", "title": "Angiotensin-converting enzyme in sarcoidosis: a British study.", "content": "Serum angiotensin-converting enzyme (ACE) activity was measured in 18 healthy controls, 26 patients with active sarcoidosis, 13 patients with inactive sarcoidosis and seven patients with extensive tuberculosis. The serum ACE activity showed no significant difference between male and female in the control or sarcoidosis groups. There was no correlation between ACE activity and age except in the female active-sarcoid group. ACE activity in the active-sarcoid group was significantly higher than in the control, inactive-sarcoid and tuberculosis groups. The ACE activities at Stages I, II and III of the disease were not significantly different.", "contents": "Angiotensin-converting enzyme in sarcoidosis: a British study. Serum angiotensin-converting enzyme (ACE) activity was measured in 18 healthy controls, 26 patients with active sarcoidosis, 13 patients with inactive sarcoidosis and seven patients with extensive tuberculosis. The serum ACE activity showed no significant difference between male and female in the control or sarcoidosis groups. There was no correlation between ACE activity and age except in the female active-sarcoid group. ACE activity in the active-sarcoid group was significantly higher than in the control, inactive-sarcoid and tuberculosis groups. The ACE activities at Stages I, II and III of the disease were not significantly different."}
{"id": "PMID:233417", "title": "[Foot-and-mouth disease in buffaloes (Bubalus bubalis, Linnaeus, 1758): search of antiantigen antibodies and isolation of the virus].", "content": "The immune response to virus-infection-associated (VIA) antigen was studied in 379 Indian buffalos (Bubalus bubalis). These animals were vaccinated three times a year with commercial acetylethyleneimine (AEI)--inactivated foot-and-mouth disease vaccines under field conditions. Two months after the last vaccination, antibody against virus-infection-associated (VIA) antigen was found in 23 per cent. Foot-and-mouth disease virus -- (FMDV) type C \"Waldmann\" was isolated from oesophageal/pharyngeal fluid of 7 samples buffalos.", "contents": "[Foot-and-mouth disease in buffaloes (Bubalus bubalis, Linnaeus, 1758): search of antiantigen antibodies and isolation of the virus]. The immune response to virus-infection-associated (VIA) antigen was studied in 379 Indian buffalos (Bubalus bubalis). These animals were vaccinated three times a year with commercial acetylethyleneimine (AEI)--inactivated foot-and-mouth disease vaccines under field conditions. Two months after the last vaccination, antibody against virus-infection-associated (VIA) antigen was found in 23 per cent. Foot-and-mouth disease virus -- (FMDV) type C \"Waldmann\" was isolated from oesophageal/pharyngeal fluid of 7 samples buffalos."}
{"id": "PMID:233422", "title": "[Immunological monitoring of patients with carcinoma of the lung. Study method and preliminary research].", "content": "It is by now an established fact that the status of the immune system stands in some relationship with the onset and evolution of malignancy. To clarify this relationship the authors investigated the immune system of patients with pulmonary carcinoma, with special regard to the functions of the T and B lymphocyte lines. After suitable explanation of their experimental protocol, which involved immunological monitoring and the study of relationships between immunological changes and the extent and histological type of malignancy, and also the effects of any treatments being administered, the authors describe the results obtained in 18 preoperative patients. The study revealed an overall diminution of cell-mediated immune activity: less strongly positive DNCB skin tests, reduced capacity for making E rosettes, reduced blast transformation with PHA. With B lymphocytes the EA rosette test was often depressed, whereas antibody titers were normal or even above normal, and the pokeweed blast test was invariable above normal values. These preliminary results show that at the time of diagnosing malignancy, the greater aggressiveness characteristic of the less differentiated cellular types, or of stages of diffuse malignancy, is associated with overpowering of cell defenses and (within certain limits) enhancement of the humoral response.", "contents": "[Immunological monitoring of patients with carcinoma of the lung. Study method and preliminary research]. It is by now an established fact that the status of the immune system stands in some relationship with the onset and evolution of malignancy. To clarify this relationship the authors investigated the immune system of patients with pulmonary carcinoma, with special regard to the functions of the T and B lymphocyte lines. After suitable explanation of their experimental protocol, which involved immunological monitoring and the study of relationships between immunological changes and the extent and histological type of malignancy, and also the effects of any treatments being administered, the authors describe the results obtained in 18 preoperative patients. The study revealed an overall diminution of cell-mediated immune activity: less strongly positive DNCB skin tests, reduced capacity for making E rosettes, reduced blast transformation with PHA. With B lymphocytes the EA rosette test was often depressed, whereas antibody titers were normal or even above normal, and the pokeweed blast test was invariable above normal values. These preliminary results show that at the time of diagnosing malignancy, the greater aggressiveness characteristic of the less differentiated cellular types, or of stages of diffuse malignancy, is associated with overpowering of cell defenses and (within certain limits) enhancement of the humoral response."}
{"id": "PMID:233425", "title": "[Three different tumors in a case of synovial sarcoma of the hand].", "content": "Examining a 74 year old female patient with a nodular goiter, a tumor of the left thenar eminence with a concurrent radiolucent swelling in the adjoining second metacarpal was found. The diagnosis was a struma nodosa with regressive marginal changes, a hypervascularized monophasic synovial sarcoma of the wrist joint, and an enchondroma of the second metacarpal bone. Following the amputation of the forearm, no radiotherapy or cytotoxic therapy was performed. After a follow-up time of one year no metastases were detected.", "contents": "[Three different tumors in a case of synovial sarcoma of the hand]. Examining a 74 year old female patient with a nodular goiter, a tumor of the left thenar eminence with a concurrent radiolucent swelling in the adjoining second metacarpal was found. The diagnosis was a struma nodosa with regressive marginal changes, a hypervascularized monophasic synovial sarcoma of the wrist joint, and an enchondroma of the second metacarpal bone. Following the amputation of the forearm, no radiotherapy or cytotoxic therapy was performed. After a follow-up time of one year no metastases were detected."}
{"id": "PMID:233431", "title": "Effects of phthalazinol (EG 626) on arterial lipolytic enzyme activities in the rat.", "content": "Phthalazinol (EG 626), a thromboxane A2 antagonist and cyclic AMP phosphodiesterase inhibitor, has been shown to prevent the atherosclerosis induced in cholesterol fed rabbits. In an attempt to clarify the antiatherosclerotic mechanism, the effects of this compound on the lipolytic enzyme activities (cholesterol esterase and lipoprotein lipase) of rat aorta were examined in vivo. Administration of EG 626 (100-200 mg/kg, per os, daily, 1-2 weeks) affected neither the aortic lysosomal cholesterol esterase nor the acid phosphatase activity, whereas the lipoprotein lipase activity was signficantly decreased by the treatment. These results suggest that with an elevation in HDL-cholesterol, a decrease in lipoprotein lipase activity after ingestion of EG 626 might contribute, at least to some extent, to the prevention of arterial lipid accumulation.", "contents": "Effects of phthalazinol (EG 626) on arterial lipolytic enzyme activities in the rat. Phthalazinol (EG 626), a thromboxane A2 antagonist and cyclic AMP phosphodiesterase inhibitor, has been shown to prevent the atherosclerosis induced in cholesterol fed rabbits. In an attempt to clarify the antiatherosclerotic mechanism, the effects of this compound on the lipolytic enzyme activities (cholesterol esterase and lipoprotein lipase) of rat aorta were examined in vivo. Administration of EG 626 (100-200 mg/kg, per os, daily, 1-2 weeks) affected neither the aortic lysosomal cholesterol esterase nor the acid phosphatase activity, whereas the lipoprotein lipase activity was signficantly decreased by the treatment. These results suggest that with an elevation in HDL-cholesterol, a decrease in lipoprotein lipase activity after ingestion of EG 626 might contribute, at least to some extent, to the prevention of arterial lipid accumulation."}
{"id": "PMID:233432", "title": "[Usage of the gel filtration method for the determination of urinary proteins (author's transl)].", "content": "The urinary proteins determination was carried out after purification by gel filtration over Sephadex rosin. The proteins eluaded react with Biuret-reagent to establish the coloured copper-proteins complex. If proteins concentrations is inferior, the proteins can be determinated by the copper-proteins complex isolation with second gel filtration and titrating Cu++ with reactives: dietildithiocarbamate or the PAR (4-(2pyridyl-azo)resorcinol monosodium salt).", "contents": "[Usage of the gel filtration method for the determination of urinary proteins (author's transl)]. The urinary proteins determination was carried out after purification by gel filtration over Sephadex rosin. The proteins eluaded react with Biuret-reagent to establish the coloured copper-proteins complex. If proteins concentrations is inferior, the proteins can be determinated by the copper-proteins complex isolation with second gel filtration and titrating Cu++ with reactives: dietildithiocarbamate or the PAR (4-(2pyridyl-azo)resorcinol monosodium salt)."}
{"id": "PMID:233434", "title": "[Occurrence of pleural mesothelioma. Chronic fibrosing pleurisy and calcified pleural plaques in Turkey in relation with environmental pollution by mineral fibers (author's transl)].", "content": "The incidence of pleural mesothelioma (PM), chronic fibrosing pleurisy (CFP) and calcified pleural plaques (CPP) has been studied in Anatolia (Turkey) in relation with environmental pollution by mineral fibers: 1) In central Anatolia, where asbestos deposits have been described, the frequency of CFP and CPP was in the range 2-25%; several cases of PM have been encountered. 2) One area (Cappadoce) is free of asbestos, but contains another kind of mineral fiber: zeolite. In this area, an outbreak of PM has been described in some villages. Among the 600 inhabitants of Karain, 28 cases of PM occurred for the period January 1975-June 1979.", "contents": "[Occurrence of pleural mesothelioma. Chronic fibrosing pleurisy and calcified pleural plaques in Turkey in relation with environmental pollution by mineral fibers (author's transl)]. The incidence of pleural mesothelioma (PM), chronic fibrosing pleurisy (CFP) and calcified pleural plaques (CPP) has been studied in Anatolia (Turkey) in relation with environmental pollution by mineral fibers: 1) In central Anatolia, where asbestos deposits have been described, the frequency of CFP and CPP was in the range 2-25%; several cases of PM have been encountered. 2) One area (Cappadoce) is free of asbestos, but contains another kind of mineral fiber: zeolite. In this area, an outbreak of PM has been described in some villages. Among the 600 inhabitants of Karain, 28 cases of PM occurred for the period January 1975-June 1979."}
{"id": "PMID:233435", "title": "[Fibre interaction with red blood cells or alveolar macrophages \"in vitro\" (author's transl)].", "content": "Haemolytic activities and effects on alveolar macrophages (AM) of various fibres were studied. UICC asbestos fibres and attapulgites either untreated or acid-leached were used. Amphiboles and commercial attapulgites were both cytotoxic on AM, but attapulgites and chrysotile were only haemolytic. Chrysotile fibres induced a release of B galactosidase; when acid treated these fibres were cytotoxic and less haemolytic. Acid treated amphiboles were more haemolytic than untreated.", "contents": "[Fibre interaction with red blood cells or alveolar macrophages \"in vitro\" (author's transl)]. Haemolytic activities and effects on alveolar macrophages (AM) of various fibres were studied. UICC asbestos fibres and attapulgites either untreated or acid-leached were used. Amphiboles and commercial attapulgites were both cytotoxic on AM, but attapulgites and chrysotile were only haemolytic. Chrysotile fibres induced a release of B galactosidase; when acid treated these fibres were cytotoxic and less haemolytic. Acid treated amphiboles were more haemolytic than untreated."}
{"id": "PMID:233438", "title": "[Danger of delayed diagnosis in severe meningeal suppurations (author's transl)].", "content": "The necessity of unequivocal diagnosis is sometimes a fatal cause of delay in the medical or neurosurgical treatment of meningeal suppurations.", "contents": "[Danger of delayed diagnosis in severe meningeal suppurations (author's transl)]. The necessity of unequivocal diagnosis is sometimes a fatal cause of delay in the medical or neurosurgical treatment of meningeal suppurations."}
{"id": "PMID:233439", "title": "[Oral contraceptive 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, there 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 or 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 mother 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 half of their reproduction period.", "contents": "[Oral contraceptive 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, there 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 or 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 mother 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 half of their reproduction period."}
{"id": "PMID:233440", "title": "[Analysis of 228 cases of multiple sclerosis (author's transl)].", "content": "The authors report some observations about 228 cases of multiple sclerosis with secure diagnosis subdivided in severe (34,6 %), common (29,8 %) and benign after the tenth year of illness (35,6 %). These observations are in agreement with classical statistic reports concerning the natural disease history : higher female incidence (64 %), average age at onset about 29,5 years, 4 main first signs (ocular [42,5 %], motor [41,5 %], ataxia [36,3 %], sensory [35 %] and remitting course [82,5 %]). Follow up study of 81 \"benign\" forms after the tenth year of the disease allows us to look at the freqwuency of \"secondarily worsening\" forms (25,7 %) and \"benign remaining\" ones until the twentieth year (10,1 %).", "contents": "[Analysis of 228 cases of multiple sclerosis (author's transl)]. The authors report some observations about 228 cases of multiple sclerosis with secure diagnosis subdivided in severe (34,6 %), common (29,8 %) and benign after the tenth year of illness (35,6 %). These observations are in agreement with classical statistic reports concerning the natural disease history : higher female incidence (64 %), average age at onset about 29,5 years, 4 main first signs (ocular [42,5 %], motor [41,5 %], ataxia [36,3 %], sensory [35 %] and remitting course [82,5 %]). Follow up study of 81 \"benign\" forms after the tenth year of the disease allows us to look at the freqwuency of \"secondarily worsening\" forms (25,7 %) and \"benign remaining\" ones until the twentieth year (10,1 %)."}
{"id": "PMID:233441", "title": "[Angiofollicular lymph node hyperplasia. About an exceptional meso-sigmoid localization (author's transl)].", "content": "The authors report the first angiofollicular Lymph-Node Hyperplasia (Castleman'tumor) case with a meso-sigmoid location. They carry out a general review of the literature on 315 observations and insist on the anatomic and evolutive aspects allowing a better understanding of the histogenesis of the lesion. The inflammatory theory, actually acknowledge by most of the authors, also seems to them the most plausible.", "contents": "[Angiofollicular lymph node hyperplasia. About an exceptional meso-sigmoid localization (author's transl)]. The authors report the first angiofollicular Lymph-Node Hyperplasia (Castleman'tumor) case with a meso-sigmoid location. They carry out a general review of the literature on 315 observations and insist on the anatomic and evolutive aspects allowing a better understanding of the histogenesis of the lesion. The inflammatory theory, actually acknowledge by most of the authors, also seems to them the most plausible."}
{"id": "PMID:233442", "title": "[Alcoholism, colic diverticular disease and metabolic disorders (author's transl)].", "content": "70 patients with colic diverticular disease and 50 control subjects were compared. Sexes and ages were matched in the two groups. Significant higher frequencies of alcoholism (P < 0,00001), hyperlipidemia (P < 0,0001), impaired oral glucose tolerance test (P < 0,001), hyperuricemia (P < 0,01) and atherosclerosis (P < 0,000001) were noted in the diverticular group. Hypothesis about pathogenesis of diverticular disease are suggested.", "contents": "[Alcoholism, colic diverticular disease and metabolic disorders (author's transl)]. 70 patients with colic diverticular disease and 50 control subjects were compared. Sexes and ages were matched in the two groups. Significant higher frequencies of alcoholism (P < 0,00001), hyperlipidemia (P < 0,0001), impaired oral glucose tolerance test (P < 0,001), hyperuricemia (P < 0,01) and atherosclerosis (P < 0,000001) were noted in the diverticular group. Hypothesis about pathogenesis of diverticular disease are suggested."}
{"id": "PMID:233443", "title": "[Screening of deafness at birth (author's transl)].", "content": "The authors studied different parameters of the hearing test proposed to detect deafness among new-borns. These parameters belong to the technic of the test itself (intensity of stimulus, repetition of the test five minutes later, during the day and the following days, characters of the reactions) and to the infant (gestational age birth weight age, disease). They found that the noise in the resuscitation room and in the usual incubators is high and perhaps injurious. Following their own experience and the results published in France and abroad, they think that the test is difficult and cannot be generalised for the moment to all newborns.", "contents": "[Screening of deafness at birth (author's transl)]. The authors studied different parameters of the hearing test proposed to detect deafness among new-borns. These parameters belong to the technic of the test itself (intensity of stimulus, repetition of the test five minutes later, during the day and the following days, characters of the reactions) and to the infant (gestational age birth weight age, disease). They found that the noise in the resuscitation room and in the usual incubators is high and perhaps injurious. Following their own experience and the results published in France and abroad, they think that the test is difficult and cannot be generalised for the moment to all newborns."}
{"id": "PMID:233444", "title": "[Double blind study of tiapride in neoplasia-related pains (author's transl)].", "content": "The antalgic effects of tiapride used by intravenous way have been evaluated in a randomized study on 30 patients with neoplasia-related pains. We noticed a partial or a complete positive response in 60 % of the cases when tiapride is given at a dose of 300 mg/day. The average efficient period was about four hours. Tolerance was good.", "contents": "[Double blind study of tiapride in neoplasia-related pains (author's transl)]. The antalgic effects of tiapride used by intravenous way have been evaluated in a randomized study on 30 patients with neoplasia-related pains. We noticed a partial or a complete positive response in 60 % of the cases when tiapride is given at a dose of 300 mg/day. The average efficient period was about four hours. Tolerance was good."}
{"id": "PMID:233445", "title": "[Are serum acid phosphatase levels of diagnostic significance in prostatic cancer? (author's transl)].", "content": "The abnormal serum level of \"prostatic\" acid phosphatases, stresses a cellular alteration but without an own specificity allowing to certify that it is related to a prostatic affection. One could expect that during the following years thanks to the immunological and electrophoretic methods one can be able to detect in serum specific enzymes issued from a tissue which is in a definite physiopathological state.", "contents": "[Are serum acid phosphatase levels of diagnostic significance in prostatic cancer? (author's transl)]. The abnormal serum level of \"prostatic\" acid phosphatases, stresses a cellular alteration but without an own specificity allowing to certify that it is related to a prostatic affection. One could expect that during the following years thanks to the immunological and electrophoretic methods one can be able to detect in serum specific enzymes issued from a tissue which is in a definite physiopathological state."}
{"id": "PMID:233446", "title": "[Coronary spasm during exercise test (author's transl)].", "content": "We thought chest pain associated with ST segment elevation during exercise test in patients with not significant coronary lesions could be related to coronary spasm. Three patients with mild coronary obstructive lesions underwent coronary arteriography during exercise test. In two patients this hypotesis was supported by angiographic documentation of the coronary spasm.", "contents": "[Coronary spasm during exercise test (author's transl)]. We thought chest pain associated with ST segment elevation during exercise test in patients with not significant coronary lesions could be related to coronary spasm. Three patients with mild coronary obstructive lesions underwent coronary arteriography during exercise test. In two patients this hypotesis was supported by angiographic documentation of the coronary spasm."}
{"id": "PMID:233450", "title": "[Adrenal cortical adenoma and arterial hypertension. Adrenal vizualisation by scintillation with 131 I 19 iodo cholesterol (author's transl)].", "content": "A case of adrenal cortical adenoma and arterial hypertension is reported. We emphasize interest of scintillation scanning with 131 I 19 iodo cholesterol, worth of routine examination when seeking for these tumors.", "contents": "[Adrenal cortical adenoma and arterial hypertension. Adrenal vizualisation by scintillation with 131 I 19 iodo cholesterol (author's transl)]. A case of adrenal cortical adenoma and arterial hypertension is reported. We emphasize interest of scintillation scanning with 131 I 19 iodo cholesterol, worth of routine examination when seeking for these tumors."}
{"id": "PMID:233449", "title": "[Dense bone metastases and hypophosphatemic osteomalacia during the course of prostatic cancer (author's transl)].", "content": "In patient bearing an advenced prostatic carcinoma with bony metastases, a major hypophosphoremia had led to the detection of an osteomalacia. As far as we know, three observations of the same syndrome have been published previously. As a pathogenic hypothesis, we propose that this tumor secret a substance which inhibit the action of vitamine D. Hypophosphoremia could result from an hyperparathyroid due to hypocalcemia.", "contents": "[Dense bone metastases and hypophosphatemic osteomalacia during the course of prostatic cancer (author's transl)]. In patient bearing an advenced prostatic carcinoma with bony metastases, a major hypophosphoremia had led to the detection of an osteomalacia. As far as we know, three observations of the same syndrome have been published previously. As a pathogenic hypothesis, we propose that this tumor secret a substance which inhibit the action of vitamine D. Hypophosphoremia could result from an hyperparathyroid due to hypocalcemia."}
{"id": "PMID:233447", "title": "[Does hyperuricemia involve a specific cardiac or renal risk? (author's transl)].", "content": "Hyperuricemia, commonly found in hypertensive patients, is a daily problem for the practitioner, especially those induced by diuretic therapies. The most divergent opinions are being given about the cardiovascular potential risk of hyper-uricemia. This article raises the problem of the use of those substances which change the metabolism of uric acid, whether they are hyper- or hypo-uricemic. It serves to remind that one must not prescribe hypo-uricemic diuretics to patients whose uricemia is increased, because they may involve serious risks, especially renal ones.", "contents": "[Does hyperuricemia involve a specific cardiac or renal risk? (author's transl)]. Hyperuricemia, commonly found in hypertensive patients, is a daily problem for the practitioner, especially those induced by diuretic therapies. The most divergent opinions are being given about the cardiovascular potential risk of hyper-uricemia. This article raises the problem of the use of those substances which change the metabolism of uric acid, whether they are hyper- or hypo-uricemic. It serves to remind that one must not prescribe hypo-uricemic diuretics to patients whose uricemia is increased, because they may involve serious risks, especially renal ones."}
{"id": "PMID:233448", "title": "[Adult teratoma of testicular and inguinal localization (author's transl)].", "content": "The purpose of the report is to present a patient in whom two adult teratomas presenting all the morphological benign features developed. The first teratoma is situated in the testis, the second is in the homolateral inguinal region. This association is very exceptional. Only a same case was found in literature. Several hypothesis about the mechanism of such lesions are discussed.", "contents": "[Adult teratoma of testicular and inguinal localization (author's transl)]. The purpose of the report is to present a patient in whom two adult teratomas presenting all the morphological benign features developed. The first teratoma is situated in the testis, the second is in the homolateral inguinal region. This association is very exceptional. Only a same case was found in literature. Several hypothesis about the mechanism of such lesions are discussed."}
{"id": "PMID:233452", "title": "[Experimental model of cerebral ischemia preventive activity of Ginkgo biloba extract (author's transl)].", "content": "Unilateral embolization of the brain was performed in rats by intracarotid injection of 4 000 radioactive microspheres (50 mu). Local blood flow in hippocampus, striatum, hypothalamus and remainder of the brain were determined using the iodoantipyrine technique. Embolization resulted in a decreases in blood flow and modificationof the distribution of microflow. Furthermore, embolization produces changes in energy metabolism : particularly a fall in ATP and glucose levels and an increase in lactate level. Subsequently, severe vasogenic edema developed. There was a correlation between the number of microspheres injected and the amount of edema. Pretreatment using an extracted of Ginkgo biloba leaves partially suppressed the effect of embolization. An improvement of the flow in the ischemic areas associated with an improvement of the energy metabolism explain the decreases of the edema.", "contents": "[Experimental model of cerebral ischemia preventive activity of Ginkgo biloba extract (author's transl)]. Unilateral embolization of the brain was performed in rats by intracarotid injection of 4 000 radioactive microspheres (50 mu). Local blood flow in hippocampus, striatum, hypothalamus and remainder of the brain were determined using the iodoantipyrine technique. Embolization resulted in a decreases in blood flow and modificationof the distribution of microflow. Furthermore, embolization produces changes in energy metabolism : particularly a fall in ATP and glucose levels and an increase in lactate level. Subsequently, severe vasogenic edema developed. There was a correlation between the number of microspheres injected and the amount of edema. Pretreatment using an extracted of Ginkgo biloba leaves partially suppressed the effect of embolization. An improvement of the flow in the ischemic areas associated with an improvement of the energy metabolism explain the decreases of the edema."}
{"id": "PMID:233456", "title": "Duck virus hepatitis: serial passage of attenuated virus in ducklings.", "content": "The safety of three attenuated virus vaccines of proven efficacy against duck virus hepatitis was assessed by controlled laboratory studies which involved the serial transmission of the virus through groups of two-day-old ducklings known to be susceptible to the disease. Each vaccine was initially derived from a different source. Enhancement of virulence which resulted in deaths from the disease in test groups of ducklings occurred in each instance.", "contents": "Duck virus hepatitis: serial passage of attenuated virus in ducklings. The safety of three attenuated virus vaccines of proven efficacy against duck virus hepatitis was assessed by controlled laboratory studies which involved the serial transmission of the virus through groups of two-day-old ducklings known to be susceptible to the disease. Each vaccine was initially derived from a different source. Enhancement of virulence which resulted in deaths from the disease in test groups of ducklings occurred in each instance."}
{"id": "PMID:233457", "title": "Detection and changes of nucleotide pyrophosphotransferase activity in cultures of Streptomyces griseus strains on solid media.", "content": "The occurrence of nucleotide pyrophosphotransferase (ATP: nucleotide 5'-phosphate pyrophosphotransferase, EC 2.7.4) and the changes in its activity were studied during differentiation in cultures of two Streptomyces griseus strains grown on the surface of a solid medium. One of the strains does not sporulate and produce nucleotide pyro photransferase in submerged culture. Nucleotide pyrophosphotransferase could be detected, though in much differing amounts, in surface cultures of both strains.", "contents": "Detection and changes of nucleotide pyrophosphotransferase activity in cultures of Streptomyces griseus strains on solid media. The occurrence of nucleotide pyrophosphotransferase (ATP: nucleotide 5'-phosphate pyrophosphotransferase, EC 2.7.4) and the changes in its activity were studied during differentiation in cultures of two Streptomyces griseus strains grown on the surface of a solid medium. One of the strains does not sporulate and produce nucleotide pyro photransferase in submerged culture. Nucleotide pyrophosphotransferase could be detected, though in much differing amounts, in surface cultures of both strains."}
{"id": "PMID:233451", "title": "[Retroperitoneal perforation of a duodenal ulcer (author's transl)].", "content": "A case or retroperitoneal perforation of a duodenal ulcer is presented. Firstly was erroneously diagnosed as an acute appendicitis, and operated upon. The result were good but four successives surgical gests became necessary : first, to treat a very severe parietal infection ; after that, to resolve one very impressive gastro-intestinal hemorrhage and lastly, to treat the duodeno-cutaenous fistula and the duodenal ulcer. The published cases in the recent literature are very scanty but similar to ourselves. The difficulties of promp diagnosis, the erroneously planned first operation in seriously ill patients would be the main causes of the very high mortality.", "contents": "[Retroperitoneal perforation of a duodenal ulcer (author's transl)]. A case or retroperitoneal perforation of a duodenal ulcer is presented. Firstly was erroneously diagnosed as an acute appendicitis, and operated upon. The result were good but four successives surgical gests became necessary : first, to treat a very severe parietal infection ; after that, to resolve one very impressive gastro-intestinal hemorrhage and lastly, to treat the duodeno-cutaenous fistula and the duodenal ulcer. The published cases in the recent literature are very scanty but similar to ourselves. The difficulties of promp diagnosis, the erroneously planned first operation in seriously ill patients would be the main causes of the very high mortality."}
{"id": "PMID:233458", "title": "[Hematological observations in patients following immunostimulation through intrapleural application of Corynebacterium parvum].", "content": "The Ludwig Lung Cancer Study Group aims to investigate the role of immunotherapy as adjuvant treatment modality in operable non-small cell bronchial carcinoma. The participants are 12 european clinics and institutes. With a proven accrual of 350 patients per year the group offers a sharp tool in clinical oncology with regards to bronchial carcinoma. The accrual phase of the first trial was closed on February 2, 1979 with 475 patients, starting a new protocol on February 5, 1979. The ongoing randomized clinical trial aims to determine if intrapleural administration of corynebacterium parvum (c. p.) can increase the tumor recurrence-free interval or increase survival. Furthermore the study aims to identify high and low risk patient subgroups after biological and immunological investigations. The possibility of giving c. p. intrapleurally in humans was investigated in a phase-I-toxicity study. A dose of 7 mg has been adopted for the clinical trial since this dose combines a measureable systemic effect (increase of leucocyte and monocyte counts) with acceptable toxicity. The main morbidity was fever, flu-like symptoms and chest pain.", "contents": "[Hematological observations in patients following immunostimulation through intrapleural application of Corynebacterium parvum]. The Ludwig Lung Cancer Study Group aims to investigate the role of immunotherapy as adjuvant treatment modality in operable non-small cell bronchial carcinoma. The participants are 12 european clinics and institutes. With a proven accrual of 350 patients per year the group offers a sharp tool in clinical oncology with regards to bronchial carcinoma. The accrual phase of the first trial was closed on February 2, 1979 with 475 patients, starting a new protocol on February 5, 1979. The ongoing randomized clinical trial aims to determine if intrapleural administration of corynebacterium parvum (c. p.) can increase the tumor recurrence-free interval or increase survival. Furthermore the study aims to identify high and low risk patient subgroups after biological and immunological investigations. The possibility of giving c. p. intrapleurally in humans was investigated in a phase-I-toxicity study. A dose of 7 mg has been adopted for the clinical trial since this dose combines a measureable systemic effect (increase of leucocyte and monocyte counts) with acceptable toxicity. The main morbidity was fever, flu-like symptoms and chest pain."}
{"id": "PMID:233459", "title": "[Prognostic significance of the cyclic AMP concentration in acute leukemias].", "content": "In patients with acute leukemia (myeloblastic, lymphoblastic, undifferentiated) proliferation kinetics and cyclic adenosine-3', 5'-monophosphate (cAMP) concentration of the leukemic cells were studied for their significance in the prediction of responsiveness to cytostatic therapy. Patients with good clinical response had significantly faster turnover and lower cAMP-levels than those who failed to respond to treatment.", "contents": "[Prognostic significance of the cyclic AMP concentration in acute leukemias]. In patients with acute leukemia (myeloblastic, lymphoblastic, undifferentiated) proliferation kinetics and cyclic adenosine-3', 5'-monophosphate (cAMP) concentration of the leukemic cells were studied for their significance in the prediction of responsiveness to cytostatic therapy. Patients with good clinical response had significantly faster turnover and lower cAMP-levels than those who failed to respond to treatment."}
{"id": "PMID:233461", "title": "[Isolation of Enterovirus 70 during an outbreak of acute hemorrhagic conjunctivitis in Algeria in 1973].", "content": "The Enterovirus 70 was isolated in Algeria in 1973 during an outbreak of acute hemorrhagic conjunctivitis. The main epidemiological features were similar to those previously described in other countries: involvement of the adults especially, mainly those living in communities, irrelevance of the different socio-economical levels of the population. The spring waters may have played a role in the transmission of the disease. The virological study draws the attention on the optimal conditions for the isolation of the virus and shows that the strains are antigenically related to those isolated in Morocco during 1971. The Enterovirus 70 was associated with adenoviruses and it was not possible to evaluate the respective role of the two groups of viruses in the determinism of the epidemic. The detection of the residual antibodies in sera collected in 1974 indicates that 58% of a group of 50 adults have antibodies against the Enterovirus 70. It is not yet possible to ascertain whether those antibodies are specific or only reflect an antigenic crossing between the Enterovirus 70 and one or several already known enteroviruses.", "contents": "[Isolation of Enterovirus 70 during an outbreak of acute hemorrhagic conjunctivitis in Algeria in 1973]. The Enterovirus 70 was isolated in Algeria in 1973 during an outbreak of acute hemorrhagic conjunctivitis. The main epidemiological features were similar to those previously described in other countries: involvement of the adults especially, mainly those living in communities, irrelevance of the different socio-economical levels of the population. The spring waters may have played a role in the transmission of the disease. The virological study draws the attention on the optimal conditions for the isolation of the virus and shows that the strains are antigenically related to those isolated in Morocco during 1971. The Enterovirus 70 was associated with adenoviruses and it was not possible to evaluate the respective role of the two groups of viruses in the determinism of the epidemic. The detection of the residual antibodies in sera collected in 1974 indicates that 58% of a group of 50 adults have antibodies against the Enterovirus 70. It is not yet possible to ascertain whether those antibodies are specific or only reflect an antigenic crossing between the Enterovirus 70 and one or several already known enteroviruses."}
{"id": "PMID:233462", "title": "[Nephroblastoma and whole-body hemihypertrophy. Relation to Wiedemann-Beckwith's syndrome].", "content": "A child with hemihypertrophy presented with Wilm's tumor at 3 years of age. History included neonatal hypoglycemia and the discovery of hepatomegaly and renal dysplasia. This case report emphasizes the close relation of body hemihypertrophy to Beckwith's syndrome, as well as the high degree to which both predispose to certain tumors.", "contents": "[Nephroblastoma and whole-body hemihypertrophy. Relation to Wiedemann-Beckwith's syndrome]. A child with hemihypertrophy presented with Wilm's tumor at 3 years of age. History included neonatal hypoglycemia and the discovery of hepatomegaly and renal dysplasia. This case report emphasizes the close relation of body hemihypertrophy to Beckwith's syndrome, as well as the high degree to which both predispose to certain tumors."}
{"id": "PMID:233467", "title": "[Hematopoiesis and changes in the RES of the spleen pulp in fibrosarcoma-bearing rats].", "content": "The transplantable fibrosarcoma of the Rat gives birth to different modifications in the splenic structures, and a strong perturbation is found within the enzymatic activities. The macrophages have an altered acid phosphatase activity. This is in marked contrast to the increase in number of the alkaline phosphatase polymorphonuclear cells, which are originated from myeloid areas in the red pulp. Lympho\u00efd-reticular cells, possessing one 5'nucleotidase activity, seem to be responsible, possibly, by forming numerous clonal systems during the development of this fibrosarcoma. The role of this separate system is discussed.", "contents": "[Hematopoiesis and changes in the RES of the spleen pulp in fibrosarcoma-bearing rats]. The transplantable fibrosarcoma of the Rat gives birth to different modifications in the splenic structures, and a strong perturbation is found within the enzymatic activities. The macrophages have an altered acid phosphatase activity. This is in marked contrast to the increase in number of the alkaline phosphatase polymorphonuclear cells, which are originated from myeloid areas in the red pulp. Lympho\u00efd-reticular cells, possessing one 5'nucleotidase activity, seem to be responsible, possibly, by forming numerous clonal systems during the development of this fibrosarcoma. The role of this separate system is discussed."}
{"id": "PMID:233463", "title": "Na+/K+-dependent adenosinetriphosphatase activity in the skin, kidney and muscle in Xenopus laevis (Daud.) adult specimens under different experimental conditions.", "content": "Xenopus laevis adult specimens were exposed to environmental changes simulating those undergone by these animals in their natural \"habitat\". After keeping groups of animals under dry conditions, some of them were returned to water. In both cases some parameters were compared with those of control animals kept in water. A lower activity in the Na+/K+-dependent ATPase of the epidermis and striated muscle was detected in \"dry\" animals with respect to the control ones or those rehydrated whereas the same ATPase activity in the kidney was higher in \"dry\" animals than in those from the other groups.", "contents": "Na+/K+-dependent adenosinetriphosphatase activity in the skin, kidney and muscle in Xenopus laevis (Daud.) adult specimens under different experimental conditions. Xenopus laevis adult specimens were exposed to environmental changes simulating those undergone by these animals in their natural \"habitat\". After keeping groups of animals under dry conditions, some of them were returned to water. In both cases some parameters were compared with those of control animals kept in water. A lower activity in the Na+/K+-dependent ATPase of the epidermis and striated muscle was detected in \"dry\" animals with respect to the control ones or those rehydrated whereas the same ATPase activity in the kidney was higher in \"dry\" animals than in those from the other groups."}
{"id": "PMID:233468", "title": "[Hormone dependence of 5'-nucleotidase histochemically detected during the development of the epididymis of the rat after birth].", "content": "5'nucleotidase activity of the apical border of the epididymal epithelium appears towards the end of the second week during postnatal development. This activity is in correlation with the activity of testicular hormone. Bilateral castration modifies it and testosterone restores this activity.", "contents": "[Hormone dependence of 5'-nucleotidase histochemically detected during the development of the epididymis of the rat after birth]. 5'nucleotidase activity of the apical border of the epididymal epithelium appears towards the end of the second week during postnatal development. This activity is in correlation with the activity of testicular hormone. Bilateral castration modifies it and testosterone restores this activity."}
{"id": "PMID:233469", "title": "Origin of mitochondrial enzymes. V. The polypeptide character and the biosynthesis of rat liver cytochrome c oxidase polypeptides by mitochondria.", "content": "Isolated rat liver mitochondria were labeled in vitro with L-[14C]leucine. Sixty percent of the incorporated radioactivity was found to reside in subunits 1, 2, and 3 of cytochrome c oxidase with apparent molecular weights of approximately 33,000, 25,000, and 20,000, respectively. The results indicate that these are the predominant products of protein synthesis under the conditions employed. The enzyme complex, as derived by immunoprecipitation, was found to contain four additional polypeptides with apparent molecular weights of 17,000, 12,500, 7000, and 3500. A comparison of electrophoretic profiles of the rat liver and beef heart enzyme reveals that the apparent molecular weights of all polypeptides are remarkably similar.", "contents": "Origin of mitochondrial enzymes. V. The polypeptide character and the biosynthesis of rat liver cytochrome c oxidase polypeptides by mitochondria. Isolated rat liver mitochondria were labeled in vitro with L-[14C]leucine. Sixty percent of the incorporated radioactivity was found to reside in subunits 1, 2, and 3 of cytochrome c oxidase with apparent molecular weights of approximately 33,000, 25,000, and 20,000, respectively. The results indicate that these are the predominant products of protein synthesis under the conditions employed. The enzyme complex, as derived by immunoprecipitation, was found to contain four additional polypeptides with apparent molecular weights of 17,000, 12,500, 7000, and 3500. A comparison of electrophoretic profiles of the rat liver and beef heart enzyme reveals that the apparent molecular weights of all polypeptides are remarkably similar."}
{"id": "PMID:233470", "title": "Lipid protein interactions in mitochondria. VIII. Effect of general anesthetics on the mobility of spin labels in lipid vesicles and mitochondrial membranes.", "content": "We have studied the effect of general anesthetics on the mobility of two stearic acid spin labels (5-doxyl stearic acid and 16-doxyl stearic acid) in bovine heart mitochondria and in phospholipid vesicles made from either mitochondrial lipids or commercial soybean phospholipids. The general anesthetics used include nonpolar compounds (alcohols, halothane, pentane, diethyl ether, chloroform) and the amphiphatic compound, ketamine. All anesthetics tested increase the mobility of the spin labels in phospholipid vesicles to a limited extent up to a concentration where the ESR spectra become those of free spin labels. On the other hand, anesthetics have a pronounced effect on mitochondrial membranes at concentrations as low as those known to produce general anesthesia; the effect is lower near the bilayer surface (5-doxyl stearic acid) and very strong in the bilayer core (16-doxyl stearic acid). The effects of anesthetics are mimicked by the detergent, Triton X-100. We suggest that the discrepancy between the action of anesthetics in mobilizing the spin labels in lipid vesicles and in membranes results from labilization of lipid protein interactions.", "contents": "Lipid protein interactions in mitochondria. VIII. Effect of general anesthetics on the mobility of spin labels in lipid vesicles and mitochondrial membranes. We have studied the effect of general anesthetics on the mobility of two stearic acid spin labels (5-doxyl stearic acid and 16-doxyl stearic acid) in bovine heart mitochondria and in phospholipid vesicles made from either mitochondrial lipids or commercial soybean phospholipids. The general anesthetics used include nonpolar compounds (alcohols, halothane, pentane, diethyl ether, chloroform) and the amphiphatic compound, ketamine. All anesthetics tested increase the mobility of the spin labels in phospholipid vesicles to a limited extent up to a concentration where the ESR spectra become those of free spin labels. On the other hand, anesthetics have a pronounced effect on mitochondrial membranes at concentrations as low as those known to produce general anesthesia; the effect is lower near the bilayer surface (5-doxyl stearic acid) and very strong in the bilayer core (16-doxyl stearic acid). The effects of anesthetics are mimicked by the detergent, Triton X-100. We suggest that the discrepancy between the action of anesthetics in mobilizing the spin labels in lipid vesicles and in membranes results from labilization of lipid protein interactions."}
{"id": "PMID:233472", "title": "Detection of conformational changes in complex III of the respiratory chain by a maleimido spin label.", "content": "Changes in the conformation of Complex III (CoQH2-cytochrome c reductase) of the mitochondrial respiratory chain were detected upon oxidoreduction using the nitroxide spin label, 3-(maleimidomethyl)-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl. EPR spectra of the spin label show a transition from a greater to a lesser degree of immobilization when the labeled enzyme, reduced either with ascorbate or sodium dithionite, is oxidized with potassium ferricyanide or ferricytochrome c. These observations are interpreted to indicate that Complex III is more compact in the reduced state at least in the locality of the spin label. An apparent increase in the concentration of total spins during oxidation of the complex suggests change in the interaction between the spin label and other paramagnetic centers and not an oxidation of spin label, itself, since reduced free spin label could not be reoxidized. Addition of antimycin A had no effect on the EPR spectrum of the spin-labeled enzyme, indicating that this inhibitor does not initiate a conformational change in the region of the spin label. Experiments in which N-ethyl-[2-3H] maleimide was bound to Complex III show that binding occurs primarily to a subunit with a molecular weight of 45,000. Although no qualitative differences were observed, it was found that less radioactivity appears in samples reduced with dithionite than in those reduced with ascorbate. This difference appears to be caused by decomposition products of dithionite.", "contents": "Detection of conformational changes in complex III of the respiratory chain by a maleimido spin label. Changes in the conformation of Complex III (CoQH2-cytochrome c reductase) of the mitochondrial respiratory chain were detected upon oxidoreduction using the nitroxide spin label, 3-(maleimidomethyl)-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl. EPR spectra of the spin label show a transition from a greater to a lesser degree of immobilization when the labeled enzyme, reduced either with ascorbate or sodium dithionite, is oxidized with potassium ferricyanide or ferricytochrome c. These observations are interpreted to indicate that Complex III is more compact in the reduced state at least in the locality of the spin label. An apparent increase in the concentration of total spins during oxidation of the complex suggests change in the interaction between the spin label and other paramagnetic centers and not an oxidation of spin label, itself, since reduced free spin label could not be reoxidized. Addition of antimycin A had no effect on the EPR spectrum of the spin-labeled enzyme, indicating that this inhibitor does not initiate a conformational change in the region of the spin label. Experiments in which N-ethyl-[2-3H] maleimide was bound to Complex III show that binding occurs primarily to a subunit with a molecular weight of 45,000. Although no qualitative differences were observed, it was found that less radioactivity appears in samples reduced with dithionite than in those reduced with ascorbate. This difference appears to be caused by decomposition products of dithionite."}
{"id": "PMID:233473", "title": "Presence of tolyl-specific IgE and absence of IgG antibodies in workers exposed to toluene diisocyanate.", "content": "Independent immunoenzymatic and radioimmunoassay techniques indicated the absence of tolyl-specific IgG antibodies in sera from 25 workers with long-term exposure to toluene diisocyanate (TDI). Five of these workers were clinically hypersensitive to TDI and displayed significant titers of tolyl-specific IgE antibodies in their sera.", "contents": "Presence of tolyl-specific IgE and absence of IgG antibodies in workers exposed to toluene diisocyanate. Independent immunoenzymatic and radioimmunoassay techniques indicated the absence of tolyl-specific IgG antibodies in sera from 25 workers with long-term exposure to toluene diisocyanate (TDI). Five of these workers were clinically hypersensitive to TDI and displayed significant titers of tolyl-specific IgE antibodies in their sera."}
{"id": "PMID:233474", "title": "[Examination of plasma membrane-enriched fraction from guinea pig intestinal smooth muscle by means of some marker enzymes (author's transl)].", "content": "By means of a preparation technique based on the discontinuous sucrose density gradient, subcellular fractions were isolated from guinea pig intestinal smooth muscle cells. A fraction which distributed to a 33% sucrose layer showed relatively high activities of 5'-nucleotidase, Na+ . K+-ATPase and ouabain sensitive Na+ . K+-ATPase. The fraction had a low NaN3 sensitive Mg2+-ATPase activity. On the other hand, the high activity of glucose-6-phosphatase showed a broad distribution. Though the sucrose density gradient proceeded over a series of the fine layers, cross-contamination of microsome into the 33% sucrose fraction was not reduced. To reduce microsomal cross-contamination, another procedure was employed. The homogenization time of 77000 xg sediment to be layered on the top of the sucrose density gradients was prolonged. This procedure did not change the distribution of K+ activated p-nitrophenylphosphatase, K+ activated ouabain sensitive p-nitrophenylphosphatase and ouabain sensitive Na+ . K+-ATPase activities. The peak of NADH cytochrome c reductase activity was shifted to a 38% sucrose fraction from a 33% sucrose fraction and the activity of this marker enzyme in the 33% sucrose fraction decreased to 60% of that of the prior procedure.", "contents": "[Examination of plasma membrane-enriched fraction from guinea pig intestinal smooth muscle by means of some marker enzymes (author's transl)]. By means of a preparation technique based on the discontinuous sucrose density gradient, subcellular fractions were isolated from guinea pig intestinal smooth muscle cells. A fraction which distributed to a 33% sucrose layer showed relatively high activities of 5'-nucleotidase, Na+ . K+-ATPase and ouabain sensitive Na+ . K+-ATPase. The fraction had a low NaN3 sensitive Mg2+-ATPase activity. On the other hand, the high activity of glucose-6-phosphatase showed a broad distribution. Though the sucrose density gradient proceeded over a series of the fine layers, cross-contamination of microsome into the 33% sucrose fraction was not reduced. To reduce microsomal cross-contamination, another procedure was employed. The homogenization time of 77000 xg sediment to be layered on the top of the sucrose density gradients was prolonged. This procedure did not change the distribution of K+ activated p-nitrophenylphosphatase, K+ activated ouabain sensitive p-nitrophenylphosphatase and ouabain sensitive Na+ . K+-ATPase activities. The peak of NADH cytochrome c reductase activity was shifted to a 38% sucrose fraction from a 33% sucrose fraction and the activity of this marker enzyme in the 33% sucrose fraction decreased to 60% of that of the prior procedure."}
{"id": "PMID:233471", "title": "Structure and function of H+-ATPase.", "content": "(1) Extensive studies on proton-translocating ATPase (H+-ATPase) revealed that H+-ATPase is an energy transforming device universally distributed in membranes of almost all kinds of cells. (2) Crystallization of the catalytic portion (F1) of H+-ATPase showed that F1 is a hexagonal molecule with a central hole. The diameter of F1 is about 90 A and its molecular weight is about 380,000. (3) Use of thermophilic F1 permits the complete reconstitution of F1 from its five subunits (alpha, beta, gamma, delta, epsilon) and demonstration of the gate function of the gamma delta epsilon-complex, the catalytic function of beta (supported by alpha and gamma), and the H+-translocating functions of all five subunits. (4) Studies using purified thermostable F0 showed that F0 is an H+-channel portion of H+-ATPase. The direct measurement of H+-flux through F0, sequencing of DCCD-binding protein, and isolation of F1-binding protein are described. (5) The subunit stoichiometry of F1 may be alpha 3 beta 3 gamma delta epsilon. (6) Reconstitution of stable H+-ATPase-liposomes revealed that ATP is directly synthesized by the flow of H+ driven by an electrochemical potential gradient and that H+ is translocated by ATP hydrolysis. This rules out functions for all the hypothetical components that do not belong to H+-ATPase in H+-driven ATP synthesis. The roles of conformation change and other phenomena in ATP synthesis are also discussed.", "contents": "Structure and function of H+-ATPase. (1) Extensive studies on proton-translocating ATPase (H+-ATPase) revealed that H+-ATPase is an energy transforming device universally distributed in membranes of almost all kinds of cells. (2) Crystallization of the catalytic portion (F1) of H+-ATPase showed that F1 is a hexagonal molecule with a central hole. The diameter of F1 is about 90 A and its molecular weight is about 380,000. (3) Use of thermophilic F1 permits the complete reconstitution of F1 from its five subunits (alpha, beta, gamma, delta, epsilon) and demonstration of the gate function of the gamma delta epsilon-complex, the catalytic function of beta (supported by alpha and gamma), and the H+-translocating functions of all five subunits. (4) Studies using purified thermostable F0 showed that F0 is an H+-channel portion of H+-ATPase. The direct measurement of H+-flux through F0, sequencing of DCCD-binding protein, and isolation of F1-binding protein are described. (5) The subunit stoichiometry of F1 may be alpha 3 beta 3 gamma delta epsilon. (6) Reconstitution of stable H+-ATPase-liposomes revealed that ATP is directly synthesized by the flow of H+ driven by an electrochemical potential gradient and that H+ is translocated by ATP hydrolysis. This rules out functions for all the hypothetical components that do not belong to H+-ATPase in H+-driven ATP synthesis. The roles of conformation change and other phenomena in ATP synthesis are also discussed."}
{"id": "PMID:233475", "title": "Mitochondrial function in cerebral ischemia and hypoxia: comparison of inhibitory and adaptive responses.", "content": "In cerebral ischemia, brain oxygen supply is totally exhausted within seconds. This necessitates cessation of mitochondrial electron transfer and energy (ATP) production. After certain periods of ATP deficiency of from 5 to 90 min, irreversible damage of mitochondrial membranes occurs. This results in decreased mitochondrial function, characterized by inhibited State 3 respiratory rates, low respiratory control ratios, and inhibited Ca2+ transport activities. A 30-min recirculation period of the ischemic brain tissue induces total restitution of mitochondrial respiratory capacity after complete ischemia, but not after incomplete ischemia. Regional in situ measurements of brain pyridine nucleotide redox levels, tissue ATP, and lactate concentrations indicate variable metabolic responses of different brain regions to oligemia. Macroheterogeneity from region to region, as well as microheterogeneity within a region are demonstrated. Contrary to the effect of tissue ischemia involving reduced or zero cerebral blood flow and tissue oxygenation, sublethal hypoxia alone at normal or increased levels of blood flow induces adaptation of the mitochondrial enzyme system to a new level of respiratory capacity, without any indications of inhibited mitochondrial energy production. Acute hypoxia induces increased respiratory capacities within 30-60 min. Under chronic conditions, alterations of mitochondrial cytochrome concentrations accompany the increased respiratory capacities. Instead of the decreased efficiency of mitochondrial energy-producing mechanisms induced by ischemia, hypoxia induces increased efficiency of energy production.", "contents": "Mitochondrial function in cerebral ischemia and hypoxia: comparison of inhibitory and adaptive responses. In cerebral ischemia, brain oxygen supply is totally exhausted within seconds. This necessitates cessation of mitochondrial electron transfer and energy (ATP) production. After certain periods of ATP deficiency of from 5 to 90 min, irreversible damage of mitochondrial membranes occurs. This results in decreased mitochondrial function, characterized by inhibited State 3 respiratory rates, low respiratory control ratios, and inhibited Ca2+ transport activities. A 30-min recirculation period of the ischemic brain tissue induces total restitution of mitochondrial respiratory capacity after complete ischemia, but not after incomplete ischemia. Regional in situ measurements of brain pyridine nucleotide redox levels, tissue ATP, and lactate concentrations indicate variable metabolic responses of different brain regions to oligemia. Macroheterogeneity from region to region, as well as microheterogeneity within a region are demonstrated. Contrary to the effect of tissue ischemia involving reduced or zero cerebral blood flow and tissue oxygenation, sublethal hypoxia alone at normal or increased levels of blood flow induces adaptation of the mitochondrial enzyme system to a new level of respiratory capacity, without any indications of inhibited mitochondrial energy production. Acute hypoxia induces increased respiratory capacities within 30-60 min. Under chronic conditions, alterations of mitochondrial cytochrome concentrations accompany the increased respiratory capacities. Instead of the decreased efficiency of mitochondrial energy-producing mechanisms induced by ischemia, hypoxia induces increased efficiency of energy production."}
{"id": "PMID:233477", "title": "[Epidemiology of R plasmid and transferable antibiotic-resistance (author's transl)].", "content": "The AA. review the basic characteristics of extra-chromosomal antibiotic-resistance along with research guide-lines concerning the epidemiology of R plasmids. They then report the results of their investigations on isolated Salmonellae during the years 1971-1977. While S. typhimurium and S. wien showed an high incidence of transferable antibiotic-resistance, other Salmonellae belonging to 32 different serotypes had low incidence rates.", "contents": "[Epidemiology of R plasmid and transferable antibiotic-resistance (author's transl)]. The AA. review the basic characteristics of extra-chromosomal antibiotic-resistance along with research guide-lines concerning the epidemiology of R plasmids. They then report the results of their investigations on isolated Salmonellae during the years 1971-1977. While S. typhimurium and S. wien showed an high incidence of transferable antibiotic-resistance, other Salmonellae belonging to 32 different serotypes had low incidence rates."}
{"id": "PMID:233480", "title": "Parainfluenzavirus upper respiratory tract illnesses in partially immune adult human subjects: a study at an Antarctic station.", "content": "Outbreaks of respiratory tract illnesses (RTI) in adult humans during October and November 1975 at McMurdo Station, Antarctica, were investigated by viral isolation and serologic procedures. The recovery of viral agents was enhanced by use of cell cultures in the field. Recoveries of parainfluenzaviruses types 1 and 3 and rhinoviruses were made from 10 of 39 nasal washings. Parainfluenzaviruses types 1 and 3 accounted for 50 and 30 per cent, respectively, of the total viruses recovered during October and November 1975. Acute and convalescent sera collected from 32 adult humans were examined for antiviral antibody by hemagglutination inhibition (HI) and radioimmunoassay (RIA) techniques. Serologic responses (HI and RIA) confirmed that parainfluenzaviruses were the predominent cause of RTI at McMurdo Station during that time. The temporal relationship between parainfluenzaviral diseases occurring in US communities and at McMurdo suggests that these viruses are transported to the Antarctic by personnel originating within the US. Standardization of the RIA allowed sequential assay of large numbers of sera using multiple preparations of radiolabeled indicator antibody, while ensuring the reproducibility of antiviral antibody titers to within one twofold dilution between subsequent labeled antibody preparations. The RIA detected both lower levels of virus specific antibody and more serologic responses than could be detected by HI.", "contents": "Parainfluenzavirus upper respiratory tract illnesses in partially immune adult human subjects: a study at an Antarctic station. Outbreaks of respiratory tract illnesses (RTI) in adult humans during October and November 1975 at McMurdo Station, Antarctica, were investigated by viral isolation and serologic procedures. The recovery of viral agents was enhanced by use of cell cultures in the field. Recoveries of parainfluenzaviruses types 1 and 3 and rhinoviruses were made from 10 of 39 nasal washings. Parainfluenzaviruses types 1 and 3 accounted for 50 and 30 per cent, respectively, of the total viruses recovered during October and November 1975. Acute and convalescent sera collected from 32 adult humans were examined for antiviral antibody by hemagglutination inhibition (HI) and radioimmunoassay (RIA) techniques. Serologic responses (HI and RIA) confirmed that parainfluenzaviruses were the predominent cause of RTI at McMurdo Station during that time. The temporal relationship between parainfluenzaviral diseases occurring in US communities and at McMurdo suggests that these viruses are transported to the Antarctic by personnel originating within the US. Standardization of the RIA allowed sequential assay of large numbers of sera using multiple preparations of radiolabeled indicator antibody, while ensuring the reproducibility of antiviral antibody titers to within one twofold dilution between subsequent labeled antibody preparations. The RIA detected both lower levels of virus specific antibody and more serologic responses than could be detected by HI."}
{"id": "PMID:233481", "title": "Changes in intracellular cyclic AMP levels of human peripheral blood lymphocytes in bronchial asthma.", "content": "Peripheral blood lymphocytes of asthmatic patients in the acute stage manifest low basal levels of cyclic AMP. These levels were higher in the lymphocytes of patients in remission than in controls. Trypsin treatment of the lymphocytes increased cyclic AMP content to almost the same additional activation site of the receptor in theophylline- and catecholamines-treated patients.", "contents": "Changes in intracellular cyclic AMP levels of human peripheral blood lymphocytes in bronchial asthma. Peripheral blood lymphocytes of asthmatic patients in the acute stage manifest low basal levels of cyclic AMP. These levels were higher in the lymphocytes of patients in remission than in controls. Trypsin treatment of the lymphocytes increased cyclic AMP content to almost the same additional activation site of the receptor in theophylline- and catecholamines-treated patients."}
{"id": "PMID:233478", "title": "[CNV and SEP in shoe-industry workers affected by neuropathy due to toxic effects of adhesive solvents (author's transl)].", "content": "The sensitivity of the CNV and somatosensory evoked potentials (SEP) was assessed in shoe industry workers suffering from neurotoxic effects of adhesive solvents. We have examined 21 patients with clear electroneuromiographic and clinical signs of polyneuropathy as well as EEG signs of diffuse brain damage. 10 normal volunteers served as a control group. The maximal motor conduction velocity (MMCV) was considerably reduced in all patients. The maximal sensory conduction velocity (MSCV) was in the lower normal range (or borderline) in 12 patients, whereas in 9 or more severe decrement was detected. In comparison with normal subjects, none of the patients showed clear differences in latency or amplitude of SEP components (p always greater than .2). It was very easy to elicit CNVs over all areas explored and all the 10 patients showed normal characteristics. These results, therefore, suggest that CNV and SEP are not helpful for an early diagnosis of toxic effects of the solvents on the function of the central and peripheral nervous system.", "contents": "[CNV and SEP in shoe-industry workers affected by neuropathy due to toxic effects of adhesive solvents (author's transl)]. The sensitivity of the CNV and somatosensory evoked potentials (SEP) was assessed in shoe industry workers suffering from neurotoxic effects of adhesive solvents. We have examined 21 patients with clear electroneuromiographic and clinical signs of polyneuropathy as well as EEG signs of diffuse brain damage. 10 normal volunteers served as a control group. The maximal motor conduction velocity (MMCV) was considerably reduced in all patients. The maximal sensory conduction velocity (MSCV) was in the lower normal range (or borderline) in 12 patients, whereas in 9 or more severe decrement was detected. In comparison with normal subjects, none of the patients showed clear differences in latency or amplitude of SEP components (p always greater than .2). It was very easy to elicit CNVs over all areas explored and all the 10 patients showed normal characteristics. These results, therefore, suggest that CNV and SEP are not helpful for an early diagnosis of toxic effects of the solvents on the function of the central and peripheral nervous system."}
{"id": "PMID:233487", "title": "[M\u00fcllerian papillary adeno-fibromata and m\u00fcllerian adenosarcomata. M\u00fclleromas and mixed malignant m\u00fcllerian growths contingent with benign epithelium (author's transl)].", "content": "The authors present 6 cases of m\u00fcllerian papillary adeno-fibromata (or mixed mesodermal m\u00fcllerian benign tumours) of which 4 are anatomo-clinical presentations and 2 are histological presentations, as well as 3 cases of m\u00fcllerian adenosarcoma (mixed m\u00fcllerian mesodermal tumour with stroma only sarcomatous). The study of these cases added on to those found in the literature leads to the following conclusions: The first group can be accepted. The second group will be of mild malignancy. All the same, 4 of which the sarcomatous nature is not in doubt at all (malignant from the start) recurred rapidly. Those in which the sarcomatous nature was attenuated or doubtful (15 cases) seemed to have a much longer evolution with some local recurrences. Only 3 patients have been followed up for more than 5 years. It is absolutely essential to carry out further observations before confirming for certain the prognosis of this new type of tumour.", "contents": "[M\u00fcllerian papillary adeno-fibromata and m\u00fcllerian adenosarcomata. M\u00fclleromas and mixed malignant m\u00fcllerian growths contingent with benign epithelium (author's transl)]. The authors present 6 cases of m\u00fcllerian papillary adeno-fibromata (or mixed mesodermal m\u00fcllerian benign tumours) of which 4 are anatomo-clinical presentations and 2 are histological presentations, as well as 3 cases of m\u00fcllerian adenosarcoma (mixed m\u00fcllerian mesodermal tumour with stroma only sarcomatous). The study of these cases added on to those found in the literature leads to the following conclusions: The first group can be accepted. The second group will be of mild malignancy. All the same, 4 of which the sarcomatous nature is not in doubt at all (malignant from the start) recurred rapidly. Those in which the sarcomatous nature was attenuated or doubtful (15 cases) seemed to have a much longer evolution with some local recurrences. Only 3 patients have been followed up for more than 5 years. It is absolutely essential to carry out further observations before confirming for certain the prognosis of this new type of tumour."}
{"id": "PMID:233488", "title": "[Hormone receptors in breast cancer. Thoughts on the use of their determination as a test of hormone dependence in a hospital routine (author's transl)].", "content": "The determination of hormone receptors in tumour tissues including, among others, breast tumours is becoming routine examination in a greatly increasing number of clinical departments. We draw the attention of clinicians to the criteria of the quality necessary in such quantitative measurements and the limits of such an examination if it is to prove useful in directing the therapy of those clinics that use it in the light of the experience we have gained in the last 4 years.", "contents": "[Hormone receptors in breast cancer. Thoughts on the use of their determination as a test of hormone dependence in a hospital routine (author's transl)]. The determination of hormone receptors in tumour tissues including, among others, breast tumours is becoming routine examination in a greatly increasing number of clinical departments. We draw the attention of clinicians to the criteria of the quality necessary in such quantitative measurements and the limits of such an examination if it is to prove useful in directing the therapy of those clinics that use it in the light of the experience we have gained in the last 4 years."}
{"id": "PMID:233489", "title": "[A thousand obstetrical sutures of the perineum using a slow absorption synthetic suture material (author's transl)].", "content": "A thread which is absorbed slowly and which has a polyglycolic acid base has been used since 1975 in the Sainte-Foy-les-Lyon Maternity Unit to sew up episiotomies and perineal tears. The authors had 98.70 p. 100 of excellent results out of 1082 cases from the anatomic, aesthetic and functional angle. This technique appears to be a useful one in early mobilisation in obstetrics.", "contents": "[A thousand obstetrical sutures of the perineum using a slow absorption synthetic suture material (author's transl)]. A thread which is absorbed slowly and which has a polyglycolic acid base has been used since 1975 in the Sainte-Foy-les-Lyon Maternity Unit to sew up episiotomies and perineal tears. The authors had 98.70 p. 100 of excellent results out of 1082 cases from the anatomic, aesthetic and functional angle. This technique appears to be a useful one in early mobilisation in obstetrics."}
{"id": "PMID:233490", "title": "[The effect of sodium polyanethol sulfonate (SPS) on the growth of bacteria in blood cultures].", "content": "The effect of SPS on growth of bacteria in blood cultures were studied. For that reason, 752 blood cultures (in media with and without SPS) were detected and found that SPS may help to growth only micrococcus species.", "contents": "[The effect of sodium polyanethol sulfonate (SPS) on the growth of bacteria in blood cultures]. The effect of SPS on growth of bacteria in blood cultures were studied. For that reason, 752 blood cultures (in media with and without SPS) were detected and found that SPS may help to growth only micrococcus species."}
{"id": "PMID:233497", "title": "[Evaluation of the reflectometric method using the skin of the toad Bufo arenarum in vitro for the determination of plasma MSH].", "content": "The aim of the present paper was to investigate the following points, by using the reflectometric bioassay for melanocyte-stimulating hormone (MSH) with skin of the toad Bufo arenarum: (1) To study if solutions of alpha-MSH prepared in rat plasma and amphibian Ringer, or dilutions of plasma overloaded with endogenous MSH, could render in acceptable dose-response lines. 2) To investigate if ACTH at a very high level of plasma concentration could interfere in the bioassay 3) Observing if the storage of plasma could inactivate the inherent MSH activity. 4) Searching for the response of the skins along the 12 months of the year. The results showed that: Acceptable dose-response lines were obtained with the three types of dilutions and parallelism was found among the three lines. ACTH does not interfere in the assay. Almost a total inactivation of MSH was detected after storing the plasma at room temperature for 4 hours; Trasylol or low temperature preserved the hormone activity. Maximal response of the skin corresponded to the minimal concentration of 1 562 pgr/ml, during the whole year. Minimum detectable concentration varied within the range 24-390 pgr/ml, depending on the month when the study was performed.", "contents": "[Evaluation of the reflectometric method using the skin of the toad Bufo arenarum in vitro for the determination of plasma MSH]. The aim of the present paper was to investigate the following points, by using the reflectometric bioassay for melanocyte-stimulating hormone (MSH) with skin of the toad Bufo arenarum: (1) To study if solutions of alpha-MSH prepared in rat plasma and amphibian Ringer, or dilutions of plasma overloaded with endogenous MSH, could render in acceptable dose-response lines. 2) To investigate if ACTH at a very high level of plasma concentration could interfere in the bioassay 3) Observing if the storage of plasma could inactivate the inherent MSH activity. 4) Searching for the response of the skins along the 12 months of the year. The results showed that: Acceptable dose-response lines were obtained with the three types of dilutions and parallelism was found among the three lines. ACTH does not interfere in the assay. Almost a total inactivation of MSH was detected after storing the plasma at room temperature for 4 hours; Trasylol or low temperature preserved the hormone activity. Maximal response of the skin corresponded to the minimal concentration of 1 562 pgr/ml, during the whole year. Minimum detectable concentration varied within the range 24-390 pgr/ml, depending on the month when the study was performed."}
{"id": "PMID:233499", "title": "Differential beta-adrenergic sensitivity of atrial tissue assessed by chronotropic and inotropic responses to several sympathomimetic amines.", "content": "The relative inotropic and chronotropic activity of epinephrine, norepinephrine, isoproterenol, dopamine, dobutamine and ethylephrine was studied on isolated rat atria at 31 C. Dose-response curves were expressed as a percentage of the maximum response. Both atria were used for testing chronotropic effects. Inotropic dose-response curves were performed on left atria driven at 1 Hz, 1.6 Hz, 2.8 Hz and 6.6 Hz. Epinephrine and norepinephrine had a greater chronotropic action than their inotropic one throughout the range of stimulation employed. Their pD2-values changed from 8.12 +/- 0.06 and 8.05 +/- 0.05 to 7.19 +/- 0.03 and 7.14 +/- 0.05, respectively. Isoproterenol, dopamine and ethylephrine produced the same degree of chronotropic and inotropic stimulation. Dobutamine exerted the same effect on heart rate and developed tension at 1 Hz. pD2-values for dobutamine were significantly lower (p less than 0.01, p less than 0.001, p less than 0.001) when the frequency of stimulation was increased to 1.6, 2.8 and 6.6 Hz. These findings may be due to the influence of the negative staircase phenomenon, the temperature and the distribution of beta 1 and beta 2 receptors.", "contents": "Differential beta-adrenergic sensitivity of atrial tissue assessed by chronotropic and inotropic responses to several sympathomimetic amines. The relative inotropic and chronotropic activity of epinephrine, norepinephrine, isoproterenol, dopamine, dobutamine and ethylephrine was studied on isolated rat atria at 31 C. Dose-response curves were expressed as a percentage of the maximum response. Both atria were used for testing chronotropic effects. Inotropic dose-response curves were performed on left atria driven at 1 Hz, 1.6 Hz, 2.8 Hz and 6.6 Hz. Epinephrine and norepinephrine had a greater chronotropic action than their inotropic one throughout the range of stimulation employed. Their pD2-values changed from 8.12 +/- 0.06 and 8.05 +/- 0.05 to 7.19 +/- 0.03 and 7.14 +/- 0.05, respectively. Isoproterenol, dopamine and ethylephrine produced the same degree of chronotropic and inotropic stimulation. Dobutamine exerted the same effect on heart rate and developed tension at 1 Hz. pD2-values for dobutamine were significantly lower (p less than 0.01, p less than 0.001, p less than 0.001) when the frequency of stimulation was increased to 1.6, 2.8 and 6.6 Hz. These findings may be due to the influence of the negative staircase phenomenon, the temperature and the distribution of beta 1 and beta 2 receptors."}
{"id": "PMID:233517", "title": "Protein quinone complexes. Bovine plasma albumin and halogenated p-quinones.", "content": "A colloidal dispersion of chloranil in water or an aqueous solution of an amino acid shows an ESR signal characteristic of the semiquinone radical anion. The signal is broadened in the presence of bovine plasma albumin, and the available evidence supports the idea that the freedom of the free radical is restricted by a weak association with a specific site in the protein.", "contents": "Protein quinone complexes. Bovine plasma albumin and halogenated p-quinones. A colloidal dispersion of chloranil in water or an aqueous solution of an amino acid shows an ESR signal characteristic of the semiquinone radical anion. The signal is broadened in the presence of bovine plasma albumin, and the available evidence supports the idea that the freedom of the free radical is restricted by a weak association with a specific site in the protein."}
{"id": "PMID:233519", "title": "The effects of carbodiimides on functions associated with the energy-conservation mechanism in beef heart sub-mitochondrial particles.", "content": "N,N'-di-n-propyl-, N,N'di-n-butyl-, N,N'-di-n-pentyl-, N,N'di-n-hexyl-, N,N'di-n-octoyl, N,N'-dibenzhydryl-, and N,N'-dibenzhydrylcarbodiimides were synthesized. They were all effective inhibitors (2 nmoles carbodiimide per milligram protein) of the ATP-driven reduction of NAD by succinate and the ATP-driven transhydrogenase activities catalyzed by beef heart submitochondrial particles (SMP). They had no effect on the nonenergy-linked transhydrogenase and stimulated the succinate-driven aerobic transhydrogenase activity of beef heart SMP. It was concluded that they exert their effects by reacting with the N,N'-dicyclohexylcarbodiimide-binding protein. Water-soluble carbodiimides were not effective inhibitors.", "contents": "The effects of carbodiimides on functions associated with the energy-conservation mechanism in beef heart sub-mitochondrial particles. N,N'-di-n-propyl-, N,N'di-n-butyl-, N,N'-di-n-pentyl-, N,N'di-n-hexyl-, N,N'di-n-octoyl, N,N'-dibenzhydryl-, and N,N'-dibenzhydrylcarbodiimides were synthesized. They were all effective inhibitors (2 nmoles carbodiimide per milligram protein) of the ATP-driven reduction of NAD by succinate and the ATP-driven transhydrogenase activities catalyzed by beef heart submitochondrial particles (SMP). They had no effect on the nonenergy-linked transhydrogenase and stimulated the succinate-driven aerobic transhydrogenase activity of beef heart SMP. It was concluded that they exert their effects by reacting with the N,N'-dicyclohexylcarbodiimide-binding protein. Water-soluble carbodiimides were not effective inhibitors."}
{"id": "PMID:233521", "title": "[Diagnosis and therapy of hepatocellular cancer].", "content": "A patient with hepatocellular carcinoma of the right liver lobe is presented by case report. Although a right side hemihepatectomy was performed, a recidive was detected 3 months later. Since then he received adriamycin-therapy and 14 months after operation, he is almost completely free of pain. Diagnosis, and surgical as well as internal therapy, are presented.", "contents": "[Diagnosis and therapy of hepatocellular cancer]. A patient with hepatocellular carcinoma of the right liver lobe is presented by case report. Although a right side hemihepatectomy was performed, a recidive was detected 3 months later. Since then he received adriamycin-therapy and 14 months after operation, he is almost completely free of pain. Diagnosis, and surgical as well as internal therapy, are presented."}
{"id": "PMID:233522", "title": "[Preliminary data on activation of the enzyme of the metabolism of phospholipid bases in various areas of the brain].", "content": "The scope of this work was to study the effect of imydazole on base-exchange enzymic system in selected cerebral areas. We have previously demonstrated that imydazole was an activator of phosphatidylserine synthesis in slices of caudate nucleus. This effect lacked in the omogenate we had supposed that this activation by imydazole was not directed on base-exchange enzymic system, but was induced by decrease of cellular cyclic nucleotides amount. Therefore we have investigated the effect of dibutirril-AMPciclic in selected cerebral areas. In addition it was useful to state if activation by imydazole was area-specific or not.", "contents": "[Preliminary data on activation of the enzyme of the metabolism of phospholipid bases in various areas of the brain]. The scope of this work was to study the effect of imydazole on base-exchange enzymic system in selected cerebral areas. We have previously demonstrated that imydazole was an activator of phosphatidylserine synthesis in slices of caudate nucleus. This effect lacked in the omogenate we had supposed that this activation by imydazole was not directed on base-exchange enzymic system, but was induced by decrease of cellular cyclic nucleotides amount. Therefore we have investigated the effect of dibutirril-AMPciclic in selected cerebral areas. In addition it was useful to state if activation by imydazole was area-specific or not."}
{"id": "PMID:233523", "title": "[Preliminary data on the behavior of the enzyme of metabolism of phospholipid bases in human tumor preparations].", "content": "The A.A. have investigated the phospholipids base-exchange enzyme system in the solid tumours in order to state if a correlation between this activity and the variation of the cellular ciclic nucleotides amount was possible considering that these compounds have been reported to undergo a variation in tumour compared with normal tissues. They report some previous results in a lung tumour and in an endometrial carcinoma, were they have found a big increase in the PhS synthesis. Such increase was possible to be seen in the endometrial carcinoma only after a stimulation by 17-beta-estradiol and it was reversed in this case by doxorubicine. These results suggest that an alteration of the PhS synthesis should be one of numerous peculiarity of the neoplastic cell.", "contents": "[Preliminary data on the behavior of the enzyme of metabolism of phospholipid bases in human tumor preparations]. The A.A. have investigated the phospholipids base-exchange enzyme system in the solid tumours in order to state if a correlation between this activity and the variation of the cellular ciclic nucleotides amount was possible considering that these compounds have been reported to undergo a variation in tumour compared with normal tissues. They report some previous results in a lung tumour and in an endometrial carcinoma, were they have found a big increase in the PhS synthesis. Such increase was possible to be seen in the endometrial carcinoma only after a stimulation by 17-beta-estradiol and it was reversed in this case by doxorubicine. These results suggest that an alteration of the PhS synthesis should be one of numerous peculiarity of the neoplastic cell."}
{"id": "PMID:233524", "title": "[Changes in phosphatidylserine synthesis in human rectal tumors].", "content": "We have investigated the phosphatidylserine metabolism in human adenocarcinoma. This phospholipid is involved in the regulation of several enzymic activities of plasma membranes; therefore it could be useful to state if some alteration of tumour membranes propriety depend on variation of phosphatidylserine synthesis. Our results make evident that in such human tumours the phosphatidylserine synthesis is greatly augmented.", "contents": "[Changes in phosphatidylserine synthesis in human rectal tumors]. We have investigated the phosphatidylserine metabolism in human adenocarcinoma. This phospholipid is involved in the regulation of several enzymic activities of plasma membranes; therefore it could be useful to state if some alteration of tumour membranes propriety depend on variation of phosphatidylserine synthesis. Our results make evident that in such human tumours the phosphatidylserine synthesis is greatly augmented."}
{"id": "PMID:233531", "title": "Protective effects of rat splenic lymphocytes and peritoneal exudate cells on herpes simplex virus infection of rat dorsal root ganglia in culture.", "content": "An in vitro model system was developed to study the effects that immune cells might have on herpes simplex virus (HSV) infection of rat dorsal root ganglia in culture. Our results demonstrate that rat splenic lymphocytes and peritoneal exudate cells are incapable of replicating HSV even if these cells come from sensitized animals and are stimulated in vitro. Both cell preparations can offer some protection to rat dorsal root ganglia from the effects of HSV infection. The data suggest that an immunologically non-specific (not mediated by sensitized cells) type of protection is important to neurons, while an immunologically specific (mediated by sensitized cells) protection is most beneficial to fibroblasts. This system can be utilized to study the mechanism of latency since the neurons of sensory ganglia are the natural site of latent herpes virus.", "contents": "Protective effects of rat splenic lymphocytes and peritoneal exudate cells on herpes simplex virus infection of rat dorsal root ganglia in culture. An in vitro model system was developed to study the effects that immune cells might have on herpes simplex virus (HSV) infection of rat dorsal root ganglia in culture. Our results demonstrate that rat splenic lymphocytes and peritoneal exudate cells are incapable of replicating HSV even if these cells come from sensitized animals and are stimulated in vitro. Both cell preparations can offer some protection to rat dorsal root ganglia from the effects of HSV infection. The data suggest that an immunologically non-specific (not mediated by sensitized cells) type of protection is important to neurons, while an immunologically specific (mediated by sensitized cells) protection is most beneficial to fibroblasts. This system can be utilized to study the mechanism of latency since the neurons of sensory ganglia are the natural site of latent herpes virus."}
{"id": "PMID:233539", "title": "An accountability model for integrating information systems, evaluation mechanisms, and decision making processes in alcohol and drug abuse agencies.", "content": "This article has attempted to demonstrate that decision making and evaluation can be carried out in a systematic fashion only if agencies make a commitment to do so, and only if adequate systems are established. The management information system is the most expensive and most sophisticated component of the integrated model presented here. Its existence, in some fashion, is essential to the operation of the model. Contrary to what many managers may believe and practice, the management information system is not in itself the final solution to evaluation. Neither is the evaluation a panacea for all program ills. Evaluation can provide the information required to meet the ever increasing demands for agency or program accountability evaluation can also provide insights for future decisions to change or alter the allocation of resources. Such evaluation must be carefully planned and implemented; and, at the state level, can be successful only if executed in a systematic manner as suggested here. Regardless of the degree of sophistication of any system, it will work only when supported by users in the local treatment centers. If the model employed does little to serve them, it is not a model worth considering. It is with these needs in mind that this model was developed.", "contents": "An accountability model for integrating information systems, evaluation mechanisms, and decision making processes in alcohol and drug abuse agencies. This article has attempted to demonstrate that decision making and evaluation can be carried out in a systematic fashion only if agencies make a commitment to do so, and only if adequate systems are established. The management information system is the most expensive and most sophisticated component of the integrated model presented here. Its existence, in some fashion, is essential to the operation of the model. Contrary to what many managers may believe and practice, the management information system is not in itself the final solution to evaluation. Neither is the evaluation a panacea for all program ills. Evaluation can provide the information required to meet the ever increasing demands for agency or program accountability evaluation can also provide insights for future decisions to change or alter the allocation of resources. Such evaluation must be carefully planned and implemented; and, at the state level, can be successful only if executed in a systematic manner as suggested here. Regardless of the degree of sophistication of any system, it will work only when supported by users in the local treatment centers. If the model employed does little to serve them, it is not a model worth considering. It is with these needs in mind that this model was developed."}
{"id": "PMID:233540", "title": "The dynamics of K+ leakage and recovery in cerebral ischemia.", "content": "A combination of K+/DC surface electrode and a fiberoptic fluorometric probe are applied to measurements in brain during cerebral ischemia. The kinetics of the responses of extracellular K+ activity and intracellular NADH fluorescence in the gerbil cerebrum following reversible carotid ligation are measured. K+e shows a two-phase response to carotid occlusion and an extended recovery phase following recirculation. The length of the recovery phase is dependent on the duration and severity of the ischemic period. In the gerbil model the degree of communication in the anterior circulation is variable, whereas a bilateral carotid occlusion is presumed to give complete cerebral ischemia. Pyridine nucleotide fluorescence serves as an indicator of the degree of ischemia. Bilateral carotid occlusions of up to 35 minutes in duration were performed. K+e reaches 30--50 mEq/liter in the extracellular space within the first two minutes. This represents cell depolarization and equilibration of K+ activity levels. Recovery appears to be complete in terms of the ability of the system to clear raised levels of K+e from the extracellular space.", "contents": "The dynamics of K+ leakage and recovery in cerebral ischemia. A combination of K+/DC surface electrode and a fiberoptic fluorometric probe are applied to measurements in brain during cerebral ischemia. The kinetics of the responses of extracellular K+ activity and intracellular NADH fluorescence in the gerbil cerebrum following reversible carotid ligation are measured. K+e shows a two-phase response to carotid occlusion and an extended recovery phase following recirculation. The length of the recovery phase is dependent on the duration and severity of the ischemic period. In the gerbil model the degree of communication in the anterior circulation is variable, whereas a bilateral carotid occlusion is presumed to give complete cerebral ischemia. Pyridine nucleotide fluorescence serves as an indicator of the degree of ischemia. Bilateral carotid occlusions of up to 35 minutes in duration were performed. K+e reaches 30--50 mEq/liter in the extracellular space within the first two minutes. This represents cell depolarization and equilibration of K+ activity levels. Recovery appears to be complete in terms of the ability of the system to clear raised levels of K+e from the extracellular space."}
{"id": "PMID:233541", "title": "Evaluation of a new vaginal contraceptive.", "content": "A new chemical contraceptive in the form of a vaginal suppository was evaluated in a series of in vitro and in vivo tests and compared to a leading contraceptive foam and cream. Good in vitro spermicidal effect was observed, but problems in solubility and the position of the suppository against the external cervical os may lead to less clinical effectiveness if not properly evaluated prior to its use.", "contents": "Evaluation of a new vaginal contraceptive. A new chemical contraceptive in the form of a vaginal suppository was evaluated in a series of in vitro and in vivo tests and compared to a leading contraceptive foam and cream. Good in vitro spermicidal effect was observed, but problems in solubility and the position of the suppository against the external cervical os may lead to less clinical effectiveness if not properly evaluated prior to its use."}
{"id": "PMID:233545", "title": "Long-term effects of metaproterenol in asthmatic children.", "content": "Oral metaproterenol was administered daily for 3 months to asthmatic children. The study was designed to determine whether chronic tolerance developed to this drug. Initial and final crossovers on the first 2 and the last 2 days of the investigation to a test dose of metaproterenol and placebo failed to show tolerance as indicated by improvement in lung volumes and dynamic mechanics of breathing after metaproterenol. Forced expiratory volume in 1 sec was the test most consistent in demonstrating bronchodilation; the action of metaproterenol. Forced expiratory volume in 1 sec was the test most consistent in demonstrating bronchodilation; the action of metaproterenol appeared to last at least 5 hours as measured by this test. T of distribution of ventilation, e.g., single- and multiple-breath nitrogen washout tests, were not consistently altered by metaproterenol. These tests did not appear to be sufficiently sensitive to detect improvement even when airway resistance decreased and forced expiratory volume in 1 sec increased toward the normal range.", "contents": "Long-term effects of metaproterenol in asthmatic children. Oral metaproterenol was administered daily for 3 months to asthmatic children. The study was designed to determine whether chronic tolerance developed to this drug. Initial and final crossovers on the first 2 and the last 2 days of the investigation to a test dose of metaproterenol and placebo failed to show tolerance as indicated by improvement in lung volumes and dynamic mechanics of breathing after metaproterenol. Forced expiratory volume in 1 sec was the test most consistent in demonstrating bronchodilation; the action of metaproterenol. Forced expiratory volume in 1 sec was the test most consistent in demonstrating bronchodilation; the action of metaproterenol appeared to last at least 5 hours as measured by this test. T of distribution of ventilation, e.g., single- and multiple-breath nitrogen washout tests, were not consistently altered by metaproterenol. These tests did not appear to be sufficiently sensitive to detect improvement even when airway resistance decreased and forced expiratory volume in 1 sec increased toward the normal range."}
{"id": "PMID:233550", "title": "The synthesis and metabolism of the lipoproteins implicated in atherosclerosis.", "content": "The basic concepts of lipoprotein biogenesis and metabolism have been briefly reviewed. Emphasis has been placed upon the distinctive roles of the liver and intestine in apolipoprotein synthesis and delivery, upon the complex interchange of lipids and apolipoproteins between lipoproteins which accompanies nascent lipoprotein maturation and metabolism within the vascular compartment, upon the primary role of these latter processes in the genesis of low density lipoprotein and upon remodelling of nascent lipoproteins to achieve a structure suitable for the function of the mature between the liver, intestine and peripheral tissues.", "contents": "The synthesis and metabolism of the lipoproteins implicated in atherosclerosis. The basic concepts of lipoprotein biogenesis and metabolism have been briefly reviewed. Emphasis has been placed upon the distinctive roles of the liver and intestine in apolipoprotein synthesis and delivery, upon the complex interchange of lipids and apolipoproteins between lipoproteins which accompanies nascent lipoprotein maturation and metabolism within the vascular compartment, upon the primary role of these latter processes in the genesis of low density lipoprotein and upon remodelling of nascent lipoproteins to achieve a structure suitable for the function of the mature between the liver, intestine and peripheral tissues."}
{"id": "PMID:233567", "title": "Relationship between Na+-dependent respiration and Na+ + K+-adenosine triphosphatase activity in the action of thyroid hormone on rat jejunal mucosa.", "content": "Administration of three successive doses of triiodothyronine (T3) (50 micrograms/100 g body wt), given on alternate days to thyroidectomized and euthyroid rats, stimulated oxygen consumption (QO2) and Na+ transport-dependent respiration (QO2 [5]) in the stripped jejunal mucosa, a preparation that consisted mostly of epithelial cells. The increase in QO2(t) accounted for 57% of the increment in QO2 in the transition from the hypothyroid to the euthyroid state and for 29% of the increment in the transition from the euthyroid to the hyperthyroid state. Administration of T3 to hypothyroid rats also increased the yield of epithelial cells. Injection of T3 into thyroidectomized and euthyroid rats increased the specific activity (at Vmax) of the (Na+ + K+)-dependent adenosine triphosphatase (NaK-ATPase) in jejunal crude membrane preparations. No significant change was recorded in the activity of Mg-ATPase in the same preparation. The ratio of QO2/NaK-ATPase and QO2(t)/NaK-ATPase in the various thyroid states remained constant, indicating proportionate increased in the respiratory and enzymatic indices. The effect of administration of T3 to thyroidectomized rats on the number of NaK-ATPase units (recovered in the crude membrane preparation) was estimated by: (a) Na+ + Mg++ + ATP-dependent binding of [3H]-ouabain to crude membrane fractions, and (b) the amount of the phosphorylated intermediate formed in the NaK-ATPase reaction from AT32P(gamma). Estimates were obtained of the maximal number of [3H]ouabain binding sites (Nm) and dissociation constants (Kd). Nm for [3H]ouabain and Nak-ATPase specific activity increased to about the same extent after T3 administration to thyroidectomized rats, with no change in the apparent Kd values. The amount of phosphorylated intermediate formed in jejunal crude membrane preparations also increased significantly. Thus, thyroid hormone administration may increase the number of active Na+pump sites in the plasma membrane. The apparent increase in the number of Na+ pump sites also correlated with the hormone dependent increases in QO2 and QO2(t).", "contents": "Relationship between Na+-dependent respiration and Na+ + K+-adenosine triphosphatase activity in the action of thyroid hormone on rat jejunal mucosa. Administration of three successive doses of triiodothyronine (T3) (50 micrograms/100 g body wt), given on alternate days to thyroidectomized and euthyroid rats, stimulated oxygen consumption (QO2) and Na+ transport-dependent respiration (QO2 [5]) in the stripped jejunal mucosa, a preparation that consisted mostly of epithelial cells. The increase in QO2(t) accounted for 57% of the increment in QO2 in the transition from the hypothyroid to the euthyroid state and for 29% of the increment in the transition from the euthyroid to the hyperthyroid state. Administration of T3 to hypothyroid rats also increased the yield of epithelial cells. Injection of T3 into thyroidectomized and euthyroid rats increased the specific activity (at Vmax) of the (Na+ + K+)-dependent adenosine triphosphatase (NaK-ATPase) in jejunal crude membrane preparations. No significant change was recorded in the activity of Mg-ATPase in the same preparation. The ratio of QO2/NaK-ATPase and QO2(t)/NaK-ATPase in the various thyroid states remained constant, indicating proportionate increased in the respiratory and enzymatic indices. The effect of administration of T3 to thyroidectomized rats on the number of NaK-ATPase units (recovered in the crude membrane preparation) was estimated by: (a) Na+ + Mg++ + ATP-dependent binding of [3H]-ouabain to crude membrane fractions, and (b) the amount of the phosphorylated intermediate formed in the NaK-ATPase reaction from AT32P(gamma). Estimates were obtained of the maximal number of [3H]ouabain binding sites (Nm) and dissociation constants (Kd). Nm for [3H]ouabain and Nak-ATPase specific activity increased to about the same extent after T3 administration to thyroidectomized rats, with no change in the apparent Kd values. The amount of phosphorylated intermediate formed in jejunal crude membrane preparations also increased significantly. Thus, thyroid hormone administration may increase the number of active Na+pump sites in the plasma membrane. The apparent increase in the number of Na+ pump sites also correlated with the hormone dependent increases in QO2 and QO2(t)."}
{"id": "PMID:233568", "title": "Interactions between quaternary lidocaine, the sodium channel gates, and tetrodotoxin.", "content": "A voltage clamp technique was used to study sodium currents and gating currents in squid axons internally perfused with the membrane impermeant sodium channel blocker, QX-314. Block by QX-314 is strongly and reversibly enhanced if a train of depolarizing pulses precedes the measurement. The depolarization-induced block is antagonized by external sodium. This antagonism provides evidence that the blocking site for the drug lies inside the channel. Depolarization-induced block of sodium current by QX-314 is accompanied by nearly twofold reduction in gating charge movement. This reduction does not add to a depolarization-induced immobilization of gating charge normally present and believed to be associated with inactivation of sodium channels. Failure to act additively suggests that both, inactivation and QX-314, affect the same component of gating charge movement. Judged from gating current measurement, a drug-blocked channel is an inactivated channel. In the presence of external tetrodotoxin and internal QX-314, gating charge movement is always half its normal size regardless of conditioning, as it QX-314 is then permanently present in the channel.", "contents": "Interactions between quaternary lidocaine, the sodium channel gates, and tetrodotoxin. A voltage clamp technique was used to study sodium currents and gating currents in squid axons internally perfused with the membrane impermeant sodium channel blocker, QX-314. Block by QX-314 is strongly and reversibly enhanced if a train of depolarizing pulses precedes the measurement. The depolarization-induced block is antagonized by external sodium. This antagonism provides evidence that the blocking site for the drug lies inside the channel. Depolarization-induced block of sodium current by QX-314 is accompanied by nearly twofold reduction in gating charge movement. This reduction does not add to a depolarization-induced immobilization of gating charge normally present and believed to be associated with inactivation of sodium channels. Failure to act additively suggests that both, inactivation and QX-314, affect the same component of gating charge movement. Judged from gating current measurement, a drug-blocked channel is an inactivated channel. In the presence of external tetrodotoxin and internal QX-314, gating charge movement is always half its normal size regardless of conditioning, as it QX-314 is then permanently present in the channel."}
{"id": "PMID:233570", "title": "Intrinsic electric fields and proton diffusion in immobilized protein membranes. Effects of electrolytes and buffers.", "content": "We present a theory for proton diffusion through an immobilized protein membrane perfused with an electrolyte and a buffer. Using a Nernst-Planck equation for each species and assuming local charge neutrality, we obtain two coupled nonlinear diffusion equations with new diffusion coefficients dependent on the concentration of all species, the diffusion constants or mobilities of the buffers and salts, the pH-derivative of the titration curves of the mobile buffer and the immobilized protein, and the derivative with respect to ionic strength of the protein titration curve. Transient time scales are locally pH-dependent because of protonation-deprotonation reactions with the fixed protein and are ionic strength-dependent because salts provide charge carriers to shield internal electric fields. Intrinsic electric fields arise proportional to the gradient of an \"effective\" charge concentration. The field may reverse locally if buffer concentrations are large (greater to or equal to 0.1 M) and if the diffusivity of the electrolyte species is sufficiently small. The \"ideal\" electrolyte case (where each species has the same diffusivity) reduces to a simple form. We apply these theoretical considerations to membranes composed of papain and bovine serum albumin (BSA) and show that intrinsic electric fields greatly enhance the mobility of protons when the ionic strength of the salts is smaller than 0.1 M. These results are consistent with experiments where pH changes are observed to depend strongly on buffer, salt, and proton concentrations in baths adjacent to the membranes.", "contents": "Intrinsic electric fields and proton diffusion in immobilized protein membranes. Effects of electrolytes and buffers. We present a theory for proton diffusion through an immobilized protein membrane perfused with an electrolyte and a buffer. Using a Nernst-Planck equation for each species and assuming local charge neutrality, we obtain two coupled nonlinear diffusion equations with new diffusion coefficients dependent on the concentration of all species, the diffusion constants or mobilities of the buffers and salts, the pH-derivative of the titration curves of the mobile buffer and the immobilized protein, and the derivative with respect to ionic strength of the protein titration curve. Transient time scales are locally pH-dependent because of protonation-deprotonation reactions with the fixed protein and are ionic strength-dependent because salts provide charge carriers to shield internal electric fields. Intrinsic electric fields arise proportional to the gradient of an \"effective\" charge concentration. The field may reverse locally if buffer concentrations are large (greater to or equal to 0.1 M) and if the diffusivity of the electrolyte species is sufficiently small. The \"ideal\" electrolyte case (where each species has the same diffusivity) reduces to a simple form. We apply these theoretical considerations to membranes composed of papain and bovine serum albumin (BSA) and show that intrinsic electric fields greatly enhance the mobility of protons when the ionic strength of the salts is smaller than 0.1 M. These results are consistent with experiments where pH changes are observed to depend strongly on buffer, salt, and proton concentrations in baths adjacent to the membranes."}
{"id": "PMID:233569", "title": "Block of sodium conductance and gating current in squid giant axons poisoned with quaternary strychnine.", "content": "Quaternary strychnine blocks sodium channels from the axoplasmic side, probably by insertion into the inner channel mouth. Block is strongly voltage dependent, being more pronounced in depolarized than in resting axons. Using potential steps as a means to modulate the level of block, we investigate strychnine effects on sodium and gating currents at +50 and -50 mV. We analyze our data in terms of the simplest possible model, wherein only an open channel may receive and retain a strychnine molecule. Our main findings are (a) block by strychnine and inactivation resemble each other and (b) block of sodium and gating currents by strychnine happen with closely similar time-courses. Our data support the hypothesis of Armstrong and Bezanilla (1977) wherein an endogenous blocking particle causes inactivation by inserting itself into the inner mouth of the sodium channel. Quaternary strychnine may act as an artificial substitute for the hypothetical endogenous blocking particle. Further, we suggest that at least 90% of the rapid asymmetrical displacement current in squid axons is sodium channel gating current, inasmuch as quaternary strychnine can block 90% of the displacement current simultaneously with sodium current.", "contents": "Block of sodium conductance and gating current in squid giant axons poisoned with quaternary strychnine. Quaternary strychnine blocks sodium channels from the axoplasmic side, probably by insertion into the inner channel mouth. Block is strongly voltage dependent, being more pronounced in depolarized than in resting axons. Using potential steps as a means to modulate the level of block, we investigate strychnine effects on sodium and gating currents at +50 and -50 mV. We analyze our data in terms of the simplest possible model, wherein only an open channel may receive and retain a strychnine molecule. Our main findings are (a) block by strychnine and inactivation resemble each other and (b) block of sodium and gating currents by strychnine happen with closely similar time-courses. Our data support the hypothesis of Armstrong and Bezanilla (1977) wherein an endogenous blocking particle causes inactivation by inserting itself into the inner mouth of the sodium channel. Quaternary strychnine may act as an artificial substitute for the hypothetical endogenous blocking particle. Further, we suggest that at least 90% of the rapid asymmetrical displacement current in squid axons is sodium channel gating current, inasmuch as quaternary strychnine can block 90% of the displacement current simultaneously with sodium current."}
{"id": "PMID:233571", "title": "Proton T1 study of coverage parameter changes in tissues from tumor-bearing mice.", "content": "measurements of water proton spin-lattice relaxation time, T1, at 20 and -15 degrees C have been performed in spleen, kidney, liver, and muscle tissues from tumor-bearing mice, as well as in tumors grown in their dorsal subcutaneous tissues. All mice used were either from the C3H/HeJ or BALB/c strain. At - 15 degrees C the T1's of tissues of a given type from tumor-bearing and healthy mice are essentially the same. It is shown that in spleen the increased T1 from tumor-bearing mice can only be explained in terms of a large change in the water coverage parameter of macromolecules. In liver, muscle, and tumors the increased water content accounts for the changes in T1, while kidney represents an intermediate case.", "contents": "Proton T1 study of coverage parameter changes in tissues from tumor-bearing mice. measurements of water proton spin-lattice relaxation time, T1, at 20 and -15 degrees C have been performed in spleen, kidney, liver, and muscle tissues from tumor-bearing mice, as well as in tumors grown in their dorsal subcutaneous tissues. All mice used were either from the C3H/HeJ or BALB/c strain. At - 15 degrees C the T1's of tissues of a given type from tumor-bearing and healthy mice are essentially the same. It is shown that in spleen the increased T1 from tumor-bearing mice can only be explained in terms of a large change in the water coverage parameter of macromolecules. In liver, muscle, and tumors the increased water content accounts for the changes in T1, while kidney represents an intermediate case."}
{"id": "PMID:233572", "title": "Photodynamic induction of an oncogenic virus in vitro.", "content": "Infectious simian virus 40 (SV40) was induced from SV40-transformed hamster kidney cells by treatment with proflavine and visible fluorescent light. The optimum levels of SV40 induced were about three orders of magnitude above spontaneous background levels observed with untreated cells. No virus induction above background levels was found by treatment of cells with either proflavine or light alone.", "contents": "Photodynamic induction of an oncogenic virus in vitro. Infectious simian virus 40 (SV40) was induced from SV40-transformed hamster kidney cells by treatment with proflavine and visible fluorescent light. The optimum levels of SV40 induced were about three orders of magnitude above spontaneous background levels observed with untreated cells. No virus induction above background levels was found by treatment of cells with either proflavine or light alone."}
{"id": "PMID:233573", "title": "Development of electron spin polarization in photosynthetic electron transfer by the radical pair mechanism.", "content": "We have extended the radical pair theory to treat systems of membrane-bound radicals with g tensor anisotropy. Analysis of the polarized electron paramagnetic resonance (EPR) signals of P700+, originating from photosystem I of higher plants, in terms of the radical pair mechanism provides information about the sequence of early electron acceptors. To account for the orientation dependence of the line shape and integrated area of this polarized signal, we propose the electron transfer sequence to be P700 leads to A1 leads to X leads to Fd(A, B), where A1 is a small organic molecule (possibly chlorophyll), X is the acceptor species observed recently in low-temperature EPR studies, and Fd(A, B) are the ferredoxin iron-sulfur centers A and B. Our calculations provide information about the life-times of A1-, and X-, and their exchange interactions with P700+. We also find supporting evidence for the orientation of X- in the thylakoid membrane reported recently by G. C. Dismukes and K. Sauer (Biochim. Biophys. Acta. 504:431-445.).", "contents": "Development of electron spin polarization in photosynthetic electron transfer by the radical pair mechanism. We have extended the radical pair theory to treat systems of membrane-bound radicals with g tensor anisotropy. Analysis of the polarized electron paramagnetic resonance (EPR) signals of P700+, originating from photosystem I of higher plants, in terms of the radical pair mechanism provides information about the sequence of early electron acceptors. To account for the orientation dependence of the line shape and integrated area of this polarized signal, we propose the electron transfer sequence to be P700 leads to A1 leads to X leads to Fd(A, B), where A1 is a small organic molecule (possibly chlorophyll), X is the acceptor species observed recently in low-temperature EPR studies, and Fd(A, B) are the ferredoxin iron-sulfur centers A and B. Our calculations provide information about the life-times of A1-, and X-, and their exchange interactions with P700+. We also find supporting evidence for the orientation of X- in the thylakoid membrane reported recently by G. C. Dismukes and K. Sauer (Biochim. Biophys. Acta. 504:431-445.)."}
{"id": "PMID:233574", "title": "Crystalline state disorder and hyperfine component line widths in ferric hemoglobin chains.", "content": "In X-band electron paramagnetic resonance spectra from single crystals of horse ferric hemoglobin, observed line widths at the low- and high-field extrema are 30 and 24 g, and as much as 400 G in the intermediate region. This behavior is similar to that of ferric myoglobin. Due to large anisotropy in the g-tensors, the line width variation can be accounted for on the basis of heme orientation disorder. This disorder is characterized by an angle, determined here by two independent methods. In these computations Gaussian disorder on a sphere is assumed. The disorder angle is found to be constant on the sphere and about 4 degrees for both alpha- and beta- chains. Treatment of crystals with heavy water (buffer) increases the disorder. Since ligand nitrogen hyperfine couplings are available from hemoglobin electron nuclear double resonance, single crystal electron paramagnetic resonance spectra can be simulated by superimposing hyperfine bands, where the line width of the component bands is a variable and the disorder model above is employed. Comparison with observed resonances fixes the hyperfine component line widths. These component line widths from ferric hemoglobin in the crystalline state are found to be smaller than those in frozen solution.", "contents": "Crystalline state disorder and hyperfine component line widths in ferric hemoglobin chains. In X-band electron paramagnetic resonance spectra from single crystals of horse ferric hemoglobin, observed line widths at the low- and high-field extrema are 30 and 24 g, and as much as 400 G in the intermediate region. This behavior is similar to that of ferric myoglobin. Due to large anisotropy in the g-tensors, the line width variation can be accounted for on the basis of heme orientation disorder. This disorder is characterized by an angle, determined here by two independent methods. In these computations Gaussian disorder on a sphere is assumed. The disorder angle is found to be constant on the sphere and about 4 degrees for both alpha- and beta- chains. Treatment of crystals with heavy water (buffer) increases the disorder. Since ligand nitrogen hyperfine couplings are available from hemoglobin electron nuclear double resonance, single crystal electron paramagnetic resonance spectra can be simulated by superimposing hyperfine bands, where the line width of the component bands is a variable and the disorder model above is employed. Comparison with observed resonances fixes the hyperfine component line widths. These component line widths from ferric hemoglobin in the crystalline state are found to be smaller than those in frozen solution."}
{"id": "PMID:233575", "title": "Quantitative evaluation of contributions to electron paramagnetic resonance line widths in ferric hemoglobin single crystals.", "content": "The contributions to the dipolar broadening of ferric magnetic resonances, from crystals of hemoglobin for which the atomic coordinates are known, have been calculated. The total second moment of the g = 2 resonance so determined is about 50 (MHz)2 or 5.0 G (peak-to-trough), figures consistent with the range of values found from analysis of experimental data. Two-thirds of this second moment comes from the two protons of the H2O molecule coordinated to the iron. Treatment with D2O is predicted to reduce the total second moment at g = 2 to about 25 (MHz)2, whereas the experimental measurements on single crystals show no decrease. If the structure of the tetramer is assumed to be the same when in solution as in the crystal, the total second moment is readily redetermined for hemoglobin in solution; the value so obtained is found to be significantly smaller than that from analysis of the g = 2 resonance measured in frozen solution. These two unexpected observations can be explained in terms of distributions in spin Hamiltonian parameters, the spread depending upon the nature of the sample--crystal or solution, ordinary or heavy water-treated. This distribution in H2O and D2O solutions appears to be about the same, since the measured differences in component line width agree with the calculated difference in dipolar contributions.", "contents": "Quantitative evaluation of contributions to electron paramagnetic resonance line widths in ferric hemoglobin single crystals. The contributions to the dipolar broadening of ferric magnetic resonances, from crystals of hemoglobin for which the atomic coordinates are known, have been calculated. The total second moment of the g = 2 resonance so determined is about 50 (MHz)2 or 5.0 G (peak-to-trough), figures consistent with the range of values found from analysis of experimental data. Two-thirds of this second moment comes from the two protons of the H2O molecule coordinated to the iron. Treatment with D2O is predicted to reduce the total second moment at g = 2 to about 25 (MHz)2, whereas the experimental measurements on single crystals show no decrease. If the structure of the tetramer is assumed to be the same when in solution as in the crystal, the total second moment is readily redetermined for hemoglobin in solution; the value so obtained is found to be significantly smaller than that from analysis of the g = 2 resonance measured in frozen solution. These two unexpected observations can be explained in terms of distributions in spin Hamiltonian parameters, the spread depending upon the nature of the sample--crystal or solution, ordinary or heavy water-treated. This distribution in H2O and D2O solutions appears to be about the same, since the measured differences in component line width agree with the calculated difference in dipolar contributions."}
{"id": "PMID:233577", "title": "n-Alkanols potentiate sodium channel inactivation in squid giant axons.", "content": "The effects of n-octanol and n-decanol on nerve membrane sodium channels were examined in internally perfused, voltage-clamped squid giant axons. Both n-octanol and n-decanol almost completely eliminated the residual sodium conductance at the end of 8-ms voltage steps. In contrast, peak sodium conductance was only partially reduced. This block of peak and residual sodium conductance was very reversible and seen with both internal and external alkanol application. The differential sensitivity of peak and residual conductance to alkanol treatment was eliminated after internal pronase treatment, suggesting that n-octanol and n-decanol enhance the normal inactivation mechanism rather than directly blocking channels in a time-dependent manner.", "contents": "n-Alkanols potentiate sodium channel inactivation in squid giant axons. The effects of n-octanol and n-decanol on nerve membrane sodium channels were examined in internally perfused, voltage-clamped squid giant axons. Both n-octanol and n-decanol almost completely eliminated the residual sodium conductance at the end of 8-ms voltage steps. In contrast, peak sodium conductance was only partially reduced. This block of peak and residual sodium conductance was very reversible and seen with both internal and external alkanol application. The differential sensitivity of peak and residual conductance to alkanol treatment was eliminated after internal pronase treatment, suggesting that n-octanol and n-decanol enhance the normal inactivation mechanism rather than directly blocking channels in a time-dependent manner."}
{"id": "PMID:233578", "title": "Magnetic resonance studies of the spatial arrangement of glucose-6-phosphate and chromium (III)-adenosine diphosphate at the catalytic site of hexokinase.", "content": "The interaction of CrADP, an exchange-inert paramagnetic analogue of Mg-ADP, with yeast hexokinase has been studied by measuring the effects of CrADP on the longitudinal nuclear relaxation rate (1/T1) of the protons of water and the protons and phosphorus atom of enzyme-bound glucose-6-P. The paramagnetic effect of CrADP on 1/T1 of water protons is enhanced upon complexation with the enzyme. Titrations measuring this paramagnetic effect at several enzyme concentrations in the presence of glucose-6-P yielded a characteristic enhancement factor for 1/T1 of water protons and the dissociation constant of CrADP from the ternary enzyme . ADPCr . glucose-6-P complex. The latter value (2 mM) is similar to that obtained from kinetic inhibition studies (Danenberg and Cleland [1975]. Biochemistry. 14:28). The presence of glucose-6-P increased the enhancement of the water relaxation rate by enzyme-bound CrADP, suggesting the formation of an enzyme . CrADP . glucose-6-P complex. The existence of such a complex was confirmed by the observation of a paramagnetic effect of enzyme-bound CrADP on the l/T1 of the 31P-nucleus and protons of enzyme-bound glucose-6-P. From the paramagnetic effects of enzyme-bound CrADP on the relaxation rates of the 31P-nucleus and the carbon-bound protons of glucose-6-P in the enzyme . ADPCr . glucose-6-P complex, using the correlation time of approximately 0.7 ns, determined from the magnetic field-dependence of 1/T1 of water protons over the range 24.3-360 MHz, a Cr3+ to phosphorus distance of 6.6 +/- 0.7 A and Cr3+ to alpha- and beta-anomeric proton distances of 8.9 and 9.7 A were calculated. These results imply the absence of a direct coordination of the phosphoryl group of glucose-6-P by the nucleotide-bound metal on hexokinase but indicate van der Waals contact between a phosphoryl oxygen of glucose-6-P and the hydration sphere of the nucleotide-bound metal. The distances are consistent with a model that assumes molecular contact between the phosphorus of glucose-6-P and a beta-phosphoryl oxygen of ADP suggesting an associative phosphoryl transfer. Because after phosphorylation of ADP, the metal ion is coordinated to the transferred phosphoryl group, the overall migration of the phosphoryl group during the phosphoryl transfer is approximately 3.6 A toward the nucleotide-bound metal. Little or no catalysis of phosphoryl transfer from glucose-6-P to alpha, beta-bidentate or beta-monodentate CrADP ( less than or equal to 0.05% of the rate found with MgADP) occurred in the presence of hexokinase, as monitored by glucose formation in a coupled assay system using glucose oxidase and peroxidase. The ability of beta, gamma-bidentate CrATP to act as a substrate (Danenberg and Cleland [1975].", "contents": "Magnetic resonance studies of the spatial arrangement of glucose-6-phosphate and chromium (III)-adenosine diphosphate at the catalytic site of hexokinase. The interaction of CrADP, an exchange-inert paramagnetic analogue of Mg-ADP, with yeast hexokinase has been studied by measuring the effects of CrADP on the longitudinal nuclear relaxation rate (1/T1) of the protons of water and the protons and phosphorus atom of enzyme-bound glucose-6-P. The paramagnetic effect of CrADP on 1/T1 of water protons is enhanced upon complexation with the enzyme. Titrations measuring this paramagnetic effect at several enzyme concentrations in the presence of glucose-6-P yielded a characteristic enhancement factor for 1/T1 of water protons and the dissociation constant of CrADP from the ternary enzyme . ADPCr . glucose-6-P complex. The latter value (2 mM) is similar to that obtained from kinetic inhibition studies (Danenberg and Cleland [1975]. Biochemistry. 14:28). The presence of glucose-6-P increased the enhancement of the water relaxation rate by enzyme-bound CrADP, suggesting the formation of an enzyme . CrADP . glucose-6-P complex. The existence of such a complex was confirmed by the observation of a paramagnetic effect of enzyme-bound CrADP on the l/T1 of the 31P-nucleus and protons of enzyme-bound glucose-6-P. From the paramagnetic effects of enzyme-bound CrADP on the relaxation rates of the 31P-nucleus and the carbon-bound protons of glucose-6-P in the enzyme . ADPCr . glucose-6-P complex, using the correlation time of approximately 0.7 ns, determined from the magnetic field-dependence of 1/T1 of water protons over the range 24.3-360 MHz, a Cr3+ to phosphorus distance of 6.6 +/- 0.7 A and Cr3+ to alpha- and beta-anomeric proton distances of 8.9 and 9.7 A were calculated. These results imply the absence of a direct coordination of the phosphoryl group of glucose-6-P by the nucleotide-bound metal on hexokinase but indicate van der Waals contact between a phosphoryl oxygen of glucose-6-P and the hydration sphere of the nucleotide-bound metal. The distances are consistent with a model that assumes molecular contact between the phosphorus of glucose-6-P and a beta-phosphoryl oxygen of ADP suggesting an associative phosphoryl transfer. Because after phosphorylation of ADP, the metal ion is coordinated to the transferred phosphoryl group, the overall migration of the phosphoryl group during the phosphoryl transfer is approximately 3.6 A toward the nucleotide-bound metal. Little or no catalysis of phosphoryl transfer from glucose-6-P to alpha, beta-bidentate or beta-monodentate CrADP ( less than or equal to 0.05% of the rate found with MgADP) occurred in the presence of hexokinase, as monitored by glucose formation in a coupled assay system using glucose oxidase and peroxidase. The ability of beta, gamma-bidentate CrATP to act as a substrate (Danenberg and Cleland [1975]."}
{"id": "PMID:233579", "title": "Electrolyte transport across a simple epithelium. Steady-state and transient analysis.", "content": "A simple transporting epithelium is represented as a cellular compartment, compliant in all dimensions, and a paracellular channel, of arbitrary shape, between well-stirred mucosal ans serosal baths. The equations for mass balance, Poiseuille flow, and the Nernst-Planck equation are used to describe the continuous behavior of the system along cell and channel, whereas passive transport across membranes is given by the relations of Kedem and Katchalsky. Time-dependent terms are retained to permit study of transient phenomena. Boundary conditions at the baths demand only mass conservation and specify no a priori estimates of the system variables. A numerical model containing Na+,K+,Cl-, and impermeant cellular anions is formulated with membrane parameters taken from the literature on Necturus gallbladder. The differential equations are represented as a finite difference scheme and solved using Newton's method. It appears that apical cellular NaCl cotransport is necessary to obtain a reasonable cell chloride concentration. Investigation of the osmolality of the transepithelial flow shows that at steady state a leaky epithelium cannot separate baths of substantially different tonicity, although this does not guarantee isotonic transport between equiosmolar media. Changes in bath pressure, application of transepithelial electrical potential, and simulation of ion-substitution experiments are performed to understand the role of membrane permeabilities in determining the dynamic behavior of the epithelium.", "contents": "Electrolyte transport across a simple epithelium. Steady-state and transient analysis. A simple transporting epithelium is represented as a cellular compartment, compliant in all dimensions, and a paracellular channel, of arbitrary shape, between well-stirred mucosal ans serosal baths. The equations for mass balance, Poiseuille flow, and the Nernst-Planck equation are used to describe the continuous behavior of the system along cell and channel, whereas passive transport across membranes is given by the relations of Kedem and Katchalsky. Time-dependent terms are retained to permit study of transient phenomena. Boundary conditions at the baths demand only mass conservation and specify no a priori estimates of the system variables. A numerical model containing Na+,K+,Cl-, and impermeant cellular anions is formulated with membrane parameters taken from the literature on Necturus gallbladder. The differential equations are represented as a finite difference scheme and solved using Newton's method. It appears that apical cellular NaCl cotransport is necessary to obtain a reasonable cell chloride concentration. Investigation of the osmolality of the transepithelial flow shows that at steady state a leaky epithelium cannot separate baths of substantially different tonicity, although this does not guarantee isotonic transport between equiosmolar media. Changes in bath pressure, application of transepithelial electrical potential, and simulation of ion-substitution experiments are performed to understand the role of membrane permeabilities in determining the dynamic behavior of the epithelium."}
{"id": "PMID:233580", "title": "Modifications of sodium channel gating in Myxicola giant axons by deuterium oxide, temperature, and internal cations.", "content": "In dialyzed Myxicola axons substitution of heavy water (D2O) externally and internally slows both sodium and potassium kinetics and decreases the maximum conductances. Furthermore, this effect is strongly temperature dependent, the magnitude of the slowing produced by D2O substitution decreasing with increasing temperature over the range 3-14 degrees C with a Q10 of approximately 0.71. The relatively small magnitude of the D2O effect, combined with its strong temperature dependence, suggests that the rate limiting process producing a conducting channel involves appreciable local changes in solvent structure. Maximum conductances in the presence of D2O were decreased by approximately 30%, while the voltage dependences of both gNa and gK were not appreciably changed. In contrast to the effects of heavy water substitution on the ionic currents, membrane asymmetry currents were not altered by D2O, suggesting that gating charge movement may preceed by several steps the final transformation of the Na+ channel to a conducting state. In Myxicola axons the effect of temperature alone on asymmetry current kinetics can be well described via a simple temporal expansion equivalent to a Q10 of 2.2, which is somewhat less than the Q10 of GNa activation. The integral of membrane asymmetry current, representing maximum charge movement, is however not appreciably altered by temperature.", "contents": "Modifications of sodium channel gating in Myxicola giant axons by deuterium oxide, temperature, and internal cations. In dialyzed Myxicola axons substitution of heavy water (D2O) externally and internally slows both sodium and potassium kinetics and decreases the maximum conductances. Furthermore, this effect is strongly temperature dependent, the magnitude of the slowing produced by D2O substitution decreasing with increasing temperature over the range 3-14 degrees C with a Q10 of approximately 0.71. The relatively small magnitude of the D2O effect, combined with its strong temperature dependence, suggests that the rate limiting process producing a conducting channel involves appreciable local changes in solvent structure. Maximum conductances in the presence of D2O were decreased by approximately 30%, while the voltage dependences of both gNa and gK were not appreciably changed. In contrast to the effects of heavy water substitution on the ionic currents, membrane asymmetry currents were not altered by D2O, suggesting that gating charge movement may preceed by several steps the final transformation of the Na+ channel to a conducting state. In Myxicola axons the effect of temperature alone on asymmetry current kinetics can be well described via a simple temporal expansion equivalent to a Q10 of 2.2, which is somewhat less than the Q10 of GNa activation. The integral of membrane asymmetry current, representing maximum charge movement, is however not appreciably altered by temperature."}
{"id": "PMID:233581", "title": "Conditioning hyperpolarization-induced delays in the potassium channels of myelinated nerve.", "content": "Hyperpolarizing conditioning pulses delay the onset of potassium channel current in voltage-clamped myelinated nerve fibers. Both the development of and recovery from this conditioning are approximately exponential functions of time: the time constants are functions of the conditioning voltage. The delay is larger and develops faster for more hyperpolarized conditioning pulses. The magnitude of the delay (but not the rate of development or recovery) depends upon the test potential-small test depolarizations produce larger delays than large depolarizations. The currents with and without the conditioning pulse cannot be made to superimpose by a simple time translation.", "contents": "Conditioning hyperpolarization-induced delays in the potassium channels of myelinated nerve. Hyperpolarizing conditioning pulses delay the onset of potassium channel current in voltage-clamped myelinated nerve fibers. Both the development of and recovery from this conditioning are approximately exponential functions of time: the time constants are functions of the conditioning voltage. The delay is larger and develops faster for more hyperpolarized conditioning pulses. The magnitude of the delay (but not the rate of development or recovery) depends upon the test potential-small test depolarizations produce larger delays than large depolarizations. The currents with and without the conditioning pulse cannot be made to superimpose by a simple time translation."}
{"id": "PMID:233582", "title": "Structure of the replication fork in ultraviolet light-irradiated human cells.", "content": "The DNA extracted from xeroderma pigmentosum human fibroblasts previously irradiated with 12.5 J/m2 of UV light and pulse-labeled for 45 min with radioactive and (or) heavy precursors, was used to determine the structural characteristics of the replication fork. Density equilibrium centrifugation experiments showed that a fork moved 6 micrometer in 45 min and bypassed 3 pyrimidine dimers in both strands. The same length was covered in 15-20 min in control cells. The delay in irradiated cells was apparently due to pyrimidine dimers acting as temporary blocks to the fork movement. Evidence for this interpretation comes from kinetics of incorporation of [3H]thymidine into DNA, which show that the time necessary to attain a new stable level of DNA synthesis in irradiated cells is equivalent to that required for the replication fork to cover the interdimer distance in one strand. On the other hand, the action of S1 nuclease on DNA synthesized soon after irradiation gives rise to a bimodal distribution in neutral sucrose gradients, one peak corresponding to 43 X 10(6) daltons and the other to 3 X 10(6) daltons. These two DNA species are generated by the attack of the S1 nuclease on single-stranded regions associated with the replication fork. A possible explanation for these results is given by a model according to which there is a delayed bypass of the dimer in the leading strand and the appearance of gaps opposite pyrimidine dimers in the lagging strand, as a direct consequence of the discontinuous mode of DNA replication. In terms of the model, the DNA of 43 X 10(6) daltons corresponds to the leading strand, linked to the unreplicated branch of the forks, whereas the piece of 3 X 10(6) daltons is the intergap DNA coming from the lagging strand. Pulse and chase experiments reveal that the low molecular weight DNA grows in a pattern that suggests that more than one gap may be formed per replication fork.", "contents": "Structure of the replication fork in ultraviolet light-irradiated human cells. The DNA extracted from xeroderma pigmentosum human fibroblasts previously irradiated with 12.5 J/m2 of UV light and pulse-labeled for 45 min with radioactive and (or) heavy precursors, was used to determine the structural characteristics of the replication fork. Density equilibrium centrifugation experiments showed that a fork moved 6 micrometer in 45 min and bypassed 3 pyrimidine dimers in both strands. The same length was covered in 15-20 min in control cells. The delay in irradiated cells was apparently due to pyrimidine dimers acting as temporary blocks to the fork movement. Evidence for this interpretation comes from kinetics of incorporation of [3H]thymidine into DNA, which show that the time necessary to attain a new stable level of DNA synthesis in irradiated cells is equivalent to that required for the replication fork to cover the interdimer distance in one strand. On the other hand, the action of S1 nuclease on DNA synthesized soon after irradiation gives rise to a bimodal distribution in neutral sucrose gradients, one peak corresponding to 43 X 10(6) daltons and the other to 3 X 10(6) daltons. These two DNA species are generated by the attack of the S1 nuclease on single-stranded regions associated with the replication fork. A possible explanation for these results is given by a model according to which there is a delayed bypass of the dimer in the leading strand and the appearance of gaps opposite pyrimidine dimers in the lagging strand, as a direct consequence of the discontinuous mode of DNA replication. In terms of the model, the DNA of 43 X 10(6) daltons corresponds to the leading strand, linked to the unreplicated branch of the forks, whereas the piece of 3 X 10(6) daltons is the intergap DNA coming from the lagging strand. Pulse and chase experiments reveal that the low molecular weight DNA grows in a pattern that suggests that more than one gap may be formed per replication fork."}
{"id": "PMID:233583", "title": "Augmentation of the in vitro humoral immune response by pharmacologic agents. II: comparison of the effects of antiproliferative agents with DBcAMP.", "content": "We have compared the stimulatory activity of DBcAMP with various antiproliferative agents on the induction of the humoral immune response. When they are present only during an early stage of immune induction, DBcAMP, colcemid, cytosine-arabinoside, hydroxy urea, and high specific activity 3H-thymidine can all enhance the primary 19s antibody response to SRBC. In contrast, each of these agents inhibits the PFC response, when they are incubated with the cells during late stages of induction of humoral immunity. Because all of these agents can inhibit proliferation of cultured cells, the results suggested that DBcAMP and other agents that elevate cAMP could augment humoral immunity via their effects on cellular proliferation. However, we also found that although each agent could modulate induction of the immune response to SRBC, only DBcAMP produced a dose- and time-dependent augmentation of the response to DLF. We conclude that although antiproliferative effects of drugs may contribute to augmentation of some humoral antibody responses, this effect alone is insufficient to account for the mechanism by which agents that elevate intracellular levels of cAMP produce enhancement of humoral immunity.", "contents": "Augmentation of the in vitro humoral immune response by pharmacologic agents. II: comparison of the effects of antiproliferative agents with DBcAMP. We have compared the stimulatory activity of DBcAMP with various antiproliferative agents on the induction of the humoral immune response. When they are present only during an early stage of immune induction, DBcAMP, colcemid, cytosine-arabinoside, hydroxy urea, and high specific activity 3H-thymidine can all enhance the primary 19s antibody response to SRBC. In contrast, each of these agents inhibits the PFC response, when they are incubated with the cells during late stages of induction of humoral immunity. Because all of these agents can inhibit proliferation of cultured cells, the results suggested that DBcAMP and other agents that elevate cAMP could augment humoral immunity via their effects on cellular proliferation. However, we also found that although each agent could modulate induction of the immune response to SRBC, only DBcAMP produced a dose- and time-dependent augmentation of the response to DLF. We conclude that although antiproliferative effects of drugs may contribute to augmentation of some humoral antibody responses, this effect alone is insufficient to account for the mechanism by which agents that elevate intracellular levels of cAMP produce enhancement of humoral immunity."}
{"id": "PMID:233584", "title": "Cyclic nucleotide changes in murine lymphocytes following thymosin incubation in vitro.", "content": "Thymosin fraction 5 and a more purified acidic fraction of thymosin at a 100-fold lower concentration elevated cGMP levels, but not cAMP levels, in murine thymocytes. When both thymus and spleen lymphocytes were fractionated via a BSA gradient procedure, both cAMP and cGMP basal values varied depending on the density of the subpopulations. Thymosin Fr5 did not elevate cAMP in any thymus subpopulation of lymphocytes obtained from the BSA density gradients. The cGMP elevation due to thymosin Fr5 in thymocytes was maximal in the most buoyant thymocytes, and no elevation of cGMP was detected in nude mouse spleen lymphocytes. These results suggest that the cGMP elevation may be an early event in the thymosin-mediated differentiation of a more mature subpopulation of thymocytes. They also suggest that utilization of subpopulations may be necessary for the complete determination of the effects of agents on cyclic nucleotide values of lymphocytes.", "contents": "Cyclic nucleotide changes in murine lymphocytes following thymosin incubation in vitro. Thymosin fraction 5 and a more purified acidic fraction of thymosin at a 100-fold lower concentration elevated cGMP levels, but not cAMP levels, in murine thymocytes. When both thymus and spleen lymphocytes were fractionated via a BSA gradient procedure, both cAMP and cGMP basal values varied depending on the density of the subpopulations. Thymosin Fr5 did not elevate cAMP in any thymus subpopulation of lymphocytes obtained from the BSA density gradients. The cGMP elevation due to thymosin Fr5 in thymocytes was maximal in the most buoyant thymocytes, and no elevation of cGMP was detected in nude mouse spleen lymphocytes. These results suggest that the cGMP elevation may be an early event in the thymosin-mediated differentiation of a more mature subpopulation of thymocytes. They also suggest that utilization of subpopulations may be necessary for the complete determination of the effects of agents on cyclic nucleotide values of lymphocytes."}
{"id": "PMID:233585", "title": "Adriamycin-induced antitumor response in lethally irradiated mice.", "content": "Lethally irradiated mice pretreated with a wide range of Adriamycin (ADM) doses were tested for their in vivo antitumor response against transplanted lymphoma cells. Tumor growth, as assessed by 125IUdR uptake, was markedly impaired by treatment with ADM by a variety of different administration schedules. This ADM-induced antitumor response was largely dose-dependent, occurred regardless of route of administration, and was detectable as late as 15-30 days following drug treatment. No genetic restriction could be found to regulate the development of this response, since tumor growth inhibition occurred in syngeneic as well as allogeneic tumor-host combinations. ADM-induced antitumor response did not appear to be due to direct antitumor action by the drug, but rather to some interaction with host immune mechanisms. Antimacrophage agents, such as silica or carrageenan, abrogated the response. The possible implication of different cells as effectors of this response is discussed.", "contents": "Adriamycin-induced antitumor response in lethally irradiated mice. Lethally irradiated mice pretreated with a wide range of Adriamycin (ADM) doses were tested for their in vivo antitumor response against transplanted lymphoma cells. Tumor growth, as assessed by 125IUdR uptake, was markedly impaired by treatment with ADM by a variety of different administration schedules. This ADM-induced antitumor response was largely dose-dependent, occurred regardless of route of administration, and was detectable as late as 15-30 days following drug treatment. No genetic restriction could be found to regulate the development of this response, since tumor growth inhibition occurred in syngeneic as well as allogeneic tumor-host combinations. ADM-induced antitumor response did not appear to be due to direct antitumor action by the drug, but rather to some interaction with host immune mechanisms. Antimacrophage agents, such as silica or carrageenan, abrogated the response. The possible implication of different cells as effectors of this response is discussed."}
{"id": "PMID:233586", "title": "Increased polymorphonuclear leukocyte cGMP levels induced by the human lympholine, leukocyte migration inhibitory factor (LIF).", "content": "The possible involvement in vitro of 3', t'-cyclic GMP (cGMP) in the mechanism of action of the lymphokine, leukocyte migration inhibitory factor (LIF), was investigated. Partially purified LIF-rich supernatants, but not their control counterparts, induced a 2-fold increase in the cGMP levels of purified human polymorphonuclear (NMN) leukocytes. The effect was no influenced by heat-inactivated horse serum; it was manifested within 3 min of exposure to LIF and it subsided within 180 min. LIF and the supernatant factor responsible for the cGMP-generating effect were both rendered inactive by treatment with the serine esterase and protease inhibitor, phenylmethylsulfonyl fluoride, indicating that these factors are closely related, if not identical. A potent phosphodiesterase inhibitor, dipyridamole (2 x 10(-4) M), induced a 3- to 5-fold increase in PMN leukocyte cGMP levels, but combined treatment with purified LIF and dipyridamole did not add to this effect. This suggests that the cGMP-generating factor acts on the biochemical pathway that degrades cGMP.", "contents": "Increased polymorphonuclear leukocyte cGMP levels induced by the human lympholine, leukocyte migration inhibitory factor (LIF). The possible involvement in vitro of 3', t'-cyclic GMP (cGMP) in the mechanism of action of the lymphokine, leukocyte migration inhibitory factor (LIF), was investigated. Partially purified LIF-rich supernatants, but not their control counterparts, induced a 2-fold increase in the cGMP levels of purified human polymorphonuclear (NMN) leukocytes. The effect was no influenced by heat-inactivated horse serum; it was manifested within 3 min of exposure to LIF and it subsided within 180 min. LIF and the supernatant factor responsible for the cGMP-generating effect were both rendered inactive by treatment with the serine esterase and protease inhibitor, phenylmethylsulfonyl fluoride, indicating that these factors are closely related, if not identical. A potent phosphodiesterase inhibitor, dipyridamole (2 x 10(-4) M), induced a 3- to 5-fold increase in PMN leukocyte cGMP levels, but combined treatment with purified LIF and dipyridamole did not add to this effect. This suggests that the cGMP-generating factor acts on the biochemical pathway that degrades cGMP."}
{"id": "PMID:233591", "title": "The effect of decreased growth rate on frequency and severity of osteochondrosis in pigs.", "content": "Rapid weight gain seems to be related to high incidence and severity of osteochondrosis. For this reason the effect of weight gain on osteochondrosis was investigated. In one experiment including 18 pigs, frequency and severity of osteochondrosis in pigs on a low caloric intake and in those on a high caloric intake (ad libitum feeding) were compared. In another experiment 8 pigs from 2 litters of pigs with a mainly wild hog ancestry were studied. These pigs had a much lower growth rate than modern domestic pigs and their constitution was different. The results of these two experiments were unequivocal. Animals with a low weight gain, nutritionally or genetically induced, had an incidence of osteochondrosis which was close to zero. It was considered that the very high growth rate in the modern domestic pig is the main reason for the high incidence of osteochondrosis. High growth rate is the result of selective breeding and intensive feeding. There are some morphologic characteristics of the modern domestic pig similar to those seen in acromegaly in man and in animals treated with growth hormone.", "contents": "The effect of decreased growth rate on frequency and severity of osteochondrosis in pigs. Rapid weight gain seems to be related to high incidence and severity of osteochondrosis. For this reason the effect of weight gain on osteochondrosis was investigated. In one experiment including 18 pigs, frequency and severity of osteochondrosis in pigs on a low caloric intake and in those on a high caloric intake (ad libitum feeding) were compared. In another experiment 8 pigs from 2 litters of pigs with a mainly wild hog ancestry were studied. These pigs had a much lower growth rate than modern domestic pigs and their constitution was different. The results of these two experiments were unequivocal. Animals with a low weight gain, nutritionally or genetically induced, had an incidence of osteochondrosis which was close to zero. It was considered that the very high growth rate in the modern domestic pig is the main reason for the high incidence of osteochondrosis. High growth rate is the result of selective breeding and intensive feeding. There are some morphologic characteristics of the modern domestic pig similar to those seen in acromegaly in man and in animals treated with growth hormone."}
{"id": "PMID:233592", "title": "Heredity of osteochondrosis, body constitution and leg weakness in the pig. A correlative investigation using progeny testing.", "content": "Sixty-three boars of the Swedish Landrace and the Yorkshire breed were progeny tested. Production variables were correlated with frequency of osteochondrotic lesions at three sites, length of radius, and presence of leg weakness in 416 offspring. Osteochondrotic lesions in distal femur and humerus were found to be correlated with desirable production variables. No correlation existed between presence of osteochondrosis and leg weakness. Analysis of variance showed that breed and boar within breed influenced frequency and distribution of osteochondrosis. The pigs of the Yorkshire breed were less affected. Heritability estimates ranged from 0.14 to 0.30 for the osteochondrotic lesions at three sites. It should be noted that these figures are preliminary because of the limited number of offspring. It was concluded that a possibility exists to lower frequency of osteochondrosis in the pig with only some loss of valuable production qualities.", "contents": "Heredity of osteochondrosis, body constitution and leg weakness in the pig. A correlative investigation using progeny testing. Sixty-three boars of the Swedish Landrace and the Yorkshire breed were progeny tested. Production variables were correlated with frequency of osteochondrotic lesions at three sites, length of radius, and presence of leg weakness in 416 offspring. Osteochondrotic lesions in distal femur and humerus were found to be correlated with desirable production variables. No correlation existed between presence of osteochondrosis and leg weakness. Analysis of variance showed that breed and boar within breed influenced frequency and distribution of osteochondrosis. The pigs of the Yorkshire breed were less affected. Heritability estimates ranged from 0.14 to 0.30 for the osteochondrotic lesions at three sites. It should be noted that these figures are preliminary because of the limited number of offspring. It was concluded that a possibility exists to lower frequency of osteochondrosis in the pig with only some loss of valuable production qualities."}
{"id": "PMID:233593", "title": "Osteochondrosis in the horse. I. A clinical and radiologic investigation of osteochondritis dissecans of the knee and hock joint.", "content": "The clinical and radiologic features of osteochondritis dissecans in the knee and hock joint of horses are described. The material includes 91 horses, of which 43 had the lesion in one or both knee joints, and 48 in one or both hock joints. It was found that osteochondritis dissecans of the knee joint was more common than the one in the hock joint in thoroughbreds and halfbreds, while the lesion in the hock joint was most common in standardbred trotters. In the knee the lesion was most often located to the lateral trochlear ridge. In the hock joint the predilection site was the intermediate ridge of the tibia. The lesions were of obvious clinical importance and the knee joint was usually more severely affected than the hock joint. Prognosis was also more guarded in horses with knee joint involvement, regardless whether or not surgical treatment was instituted. Arthrotomy and removal of fragments in the osteochondral defects or of loose bodies was the standard surgical procedure. It was felt that this treatment improved prognosis somewhat, particularly in the horses with hock joint lesions. It was found that there are many similarities between osteochondritis dissecans in horses and in pigs and dogs. However, further investigation is needed to shed more light on etiology and pathogenesis and on the nature of osteochondritis dissecans in the horse.", "contents": "Osteochondrosis in the horse. I. A clinical and radiologic investigation of osteochondritis dissecans of the knee and hock joint. The clinical and radiologic features of osteochondritis dissecans in the knee and hock joint of horses are described. The material includes 91 horses, of which 43 had the lesion in one or both knee joints, and 48 in one or both hock joints. It was found that osteochondritis dissecans of the knee joint was more common than the one in the hock joint in thoroughbreds and halfbreds, while the lesion in the hock joint was most common in standardbred trotters. In the knee the lesion was most often located to the lateral trochlear ridge. In the hock joint the predilection site was the intermediate ridge of the tibia. The lesions were of obvious clinical importance and the knee joint was usually more severely affected than the hock joint. Prognosis was also more guarded in horses with knee joint involvement, regardless whether or not surgical treatment was instituted. Arthrotomy and removal of fragments in the osteochondral defects or of loose bodies was the standard surgical procedure. It was felt that this treatment improved prognosis somewhat, particularly in the horses with hock joint lesions. It was found that there are many similarities between osteochondritis dissecans in horses and in pigs and dogs. However, further investigation is needed to shed more light on etiology and pathogenesis and on the nature of osteochondritis dissecans in the horse."}
{"id": "PMID:233594", "title": "Growth and skeletal development of the pig.", "content": "Growth and skeletal development of the domestic pig (Swedish landrace and Yorkshire) are reported and the weight curve of males from birth to maturity included. Other parameters were tooth development and growth of certain bones. It was concluded that daily weight gain increases rapidly to an age of about 5 months. Sexual maturity is reached by both the male and female pig at about 5--6 months of age. At this time there is an inflection point on the weight curve. The period from 5--6 months to about 18 months of age is called adolescence. After 18 months of age the weight curve is flattened. The data from the domestic pigs were compared with the corresponding data of the wild European hog. It was found that the wild hog has a much slower weight gain.", "contents": "Growth and skeletal development of the pig. Growth and skeletal development of the domestic pig (Swedish landrace and Yorkshire) are reported and the weight curve of males from birth to maturity included. Other parameters were tooth development and growth of certain bones. It was concluded that daily weight gain increases rapidly to an age of about 5 months. Sexual maturity is reached by both the male and female pig at about 5--6 months of age. At this time there is an inflection point on the weight curve. The period from 5--6 months to about 18 months of age is called adolescence. After 18 months of age the weight curve is flattened. The data from the domestic pigs were compared with the corresponding data of the wild European hog. It was found that the wild hog has a much slower weight gain."}
{"id": "PMID:233595", "title": "Osteochondrosis in the horse. II. Pathology.", "content": "An investigation was made of the pathology of osteochondritis dissecans of young foals and horses with clinical signs of the lesion. A randomly selected material of fetuses and young foals without clinical signs was also examined. It was demonstrated that osteochondritis dissecans is primarily a cartilaginous disease, as previously described in pigs and dogs. Thickening, disturbance of endochondral ossification, degeneration and necrosis of the cartilage were the four main features of osteochondritis dissecans. Cracks and fissures occurred in the degenerated and necrotic parts of the cartilage. This led to formation of cartilage flaps and eventually to loose bodies. It was shown that small pieces of subchondral bone could be ripped off when a cartilage flap was formed. This was one explanation as to why many flaps and loose bodies contained bone in contrast to the findings in pigs and dogs. Endochondral ossification could also take place in the thickened joint cartilage in some cases. Even some loose bodies could undergo endochondral ossification if they were well nourished. Osteochondritis dissecans was often found bilaterally in the knee and hock joint and this was interpreted as an indication that osteochondritis dissecans is a manifestation of a generalized condition called osteochondrosis. Simultaneous occurrence of lesions in joints other than the knee and hock and in several metaphyseal growth plates was another indication of the generalized nature.", "contents": "Osteochondrosis in the horse. II. Pathology. An investigation was made of the pathology of osteochondritis dissecans of young foals and horses with clinical signs of the lesion. A randomly selected material of fetuses and young foals without clinical signs was also examined. It was demonstrated that osteochondritis dissecans is primarily a cartilaginous disease, as previously described in pigs and dogs. Thickening, disturbance of endochondral ossification, degeneration and necrosis of the cartilage were the four main features of osteochondritis dissecans. Cracks and fissures occurred in the degenerated and necrotic parts of the cartilage. This led to formation of cartilage flaps and eventually to loose bodies. It was shown that small pieces of subchondral bone could be ripped off when a cartilage flap was formed. This was one explanation as to why many flaps and loose bodies contained bone in contrast to the findings in pigs and dogs. Endochondral ossification could also take place in the thickened joint cartilage in some cases. Even some loose bodies could undergo endochondral ossification if they were well nourished. Osteochondritis dissecans was often found bilaterally in the knee and hock joint and this was interpreted as an indication that osteochondritis dissecans is a manifestation of a generalized condition called osteochondrosis. Simultaneous occurrence of lesions in joints other than the knee and hock and in several metaphyseal growth plates was another indication of the generalized nature."}
{"id": "PMID:233596", "title": "Osteochondrosis in growing bulls. Pathology, frequency and severity on different feedings.", "content": "Lesions typical for osteochondrosis were found in the joint cartilage and metaphyseal growth plates of growing bulls, of which many showed clinical signs of so-called leg weakness. Of 48 bulls included in the investigation, 23 were on intensive feeding and they all were found to have osteochondrosis at several locations. Of the 25 bulls of lower intensity feeding, only 13 had osteochondrosis. The lesions in those bulls were less severe than in the bulls on the high intensity feeding. At slaughter, when the lesions were inspected, the bulls on high energy feeding were much younger than the ones on the lower energy feeding. This must be kept in mind, when a comparison is made. As the bulls of the high intensity feeding were growing more rapidly, frequency and severity of osteochondrosis seemed to be correlated with rapid growth. Other etiological factors were, however, considered. A comparatively low intake of calcium in relation to daily weight increase may be one explanation for the high frequency in the bulls in high intensity feeding. Lack of exercise and large amounts of concentrates were possible explanations for the overall high frequency of osteochondrosis in the present material. The lesions in the joints and growth plates in the bulls were similar to those seen in pigs and horses. The reason why some partly or completely detached bodies contained bone is discussed. A possible connection between osteochondrosis and so-called subchondral bone cysts, as previously described in horses, is mentioned.", "contents": "Osteochondrosis in growing bulls. Pathology, frequency and severity on different feedings. Lesions typical for osteochondrosis were found in the joint cartilage and metaphyseal growth plates of growing bulls, of which many showed clinical signs of so-called leg weakness. Of 48 bulls included in the investigation, 23 were on intensive feeding and they all were found to have osteochondrosis at several locations. Of the 25 bulls of lower intensity feeding, only 13 had osteochondrosis. The lesions in those bulls were less severe than in the bulls on the high intensity feeding. At slaughter, when the lesions were inspected, the bulls on high energy feeding were much younger than the ones on the lower energy feeding. This must be kept in mind, when a comparison is made. As the bulls of the high intensity feeding were growing more rapidly, frequency and severity of osteochondrosis seemed to be correlated with rapid growth. Other etiological factors were, however, considered. A comparatively low intake of calcium in relation to daily weight increase may be one explanation for the high frequency in the bulls in high intensity feeding. Lack of exercise and large amounts of concentrates were possible explanations for the overall high frequency of osteochondrosis in the present material. The lesions in the joints and growth plates in the bulls were similar to those seen in pigs and horses. The reason why some partly or completely detached bodies contained bone is discussed. A possible connection between osteochondrosis and so-called subchondral bone cysts, as previously described in horses, is mentioned."}
{"id": "PMID:233597", "title": "Tibial dyschondroplasia (osteochondrosis) in the turkey. A morphologic investigation.", "content": "Sixty-seven Broadbreasted White Turkeys, 4 to 137 days old, were included in the investigation. Some were normal, while others were limping, and some had bowed legs. Immediately after destruction of the birds, the arteries of the legs were injected with Colorpaque, using a technique introduced by the author. The proximal part of one or both tibiae were examined radiographically, macroscopically, and microscopically. The microscopic examination included histology, microangiography, and microradiography. The normal development and morphology of the proximal tibia is presented. Thereafter an account is given of development and morphology of the tibia with dyschondroplastic lesions (retained cartilages). It was found that 39 of the 67 birds had some degree of tibial dyschondroplasia. The retained cartilage was seen in the posteromedial part of the proximal tibial metaphysis. The growth plate both of the normal and abnormal birds consisted of 3 layers of cells in order from the epiphysis--the one of proliferating cells, the one of transitional cells, and the one of hypertrophied cells. A main feature in tibial dyschondroplasia is accumulation of transitional cells, which do not have a vascular supply. By microangiographic means it was possible to demonstrate that the retained cartilage is surrounded by numerous vessels, which apparently cannot get into the cartilage. The reason for the loss of normal differentiation of the cartilage cells and concomitant disturbance of the endochondral ossification is obscure. It is speculated that changes on an ultrastructural and biochemical level are responsible for the pathologic condition. When the retained cartilage reaches a certain size, degenerative changes, necrosis, and fissures occur. Complete healing of the lesion was not seen in any of the birds, but partial disappearance of the proximal or distal part of the retained cartilage took place in some birds. It was concluded that the present investigation has shed light on the development and morphology of tibial dyschondroplasia, but it has also brought forward a number of questions about etiology. There seems to be good reason to believe that dyschondroplasia in the turkey is of similar nature as dyschondroplasia in broilers and osteochondrosis in domestic mammals.", "contents": "Tibial dyschondroplasia (osteochondrosis) in the turkey. A morphologic investigation. Sixty-seven Broadbreasted White Turkeys, 4 to 137 days old, were included in the investigation. Some were normal, while others were limping, and some had bowed legs. Immediately after destruction of the birds, the arteries of the legs were injected with Colorpaque, using a technique introduced by the author. The proximal part of one or both tibiae were examined radiographically, macroscopically, and microscopically. The microscopic examination included histology, microangiography, and microradiography. The normal development and morphology of the proximal tibia is presented. Thereafter an account is given of development and morphology of the tibia with dyschondroplastic lesions (retained cartilages). It was found that 39 of the 67 birds had some degree of tibial dyschondroplasia. The retained cartilage was seen in the posteromedial part of the proximal tibial metaphysis. The growth plate both of the normal and abnormal birds consisted of 3 layers of cells in order from the epiphysis--the one of proliferating cells, the one of transitional cells, and the one of hypertrophied cells. A main feature in tibial dyschondroplasia is accumulation of transitional cells, which do not have a vascular supply. By microangiographic means it was possible to demonstrate that the retained cartilage is surrounded by numerous vessels, which apparently cannot get into the cartilage. The reason for the loss of normal differentiation of the cartilage cells and concomitant disturbance of the endochondral ossification is obscure. It is speculated that changes on an ultrastructural and biochemical level are responsible for the pathologic condition. When the retained cartilage reaches a certain size, degenerative changes, necrosis, and fissures occur. Complete healing of the lesion was not seen in any of the birds, but partial disappearance of the proximal or distal part of the retained cartilage took place in some birds. It was concluded that the present investigation has shed light on the development and morphology of tibial dyschondroplasia, but it has also brought forward a number of questions about etiology. There seems to be good reason to believe that dyschondroplasia in the turkey is of similar nature as dyschondroplasia in broilers and osteochondrosis in domestic mammals."}
{"id": "PMID:233598", "title": "Skeletal lesions in the broiler, with special reference to dyschondroplasia (osteochondrosis). Pathology, frequency and clinical significance in two strains of birds on high and low energy feed.", "content": "The material consisted of 2,950 broilers of the variety Hybro Compact of two lines. An equal number of birds of both lines were given either a high energy feed (H) or a low energy feed (L), containing all nutrients known to be required by broilers. During the first 3 weeks, H and L starter feeds were given and thereafter H and L finishing feeds. At 21, 35, and 45 days of age, the birds were weighed in groups, and feed conversion calculated. At 21 days of age, the frequency of crooked toes and swollen hocks was registered. Birds were taken from each group for necropsy at regular intervals. Both clinically normal birds and those with locomotor disturbances were selected for necropsy, including radiographic examination. With the exception of 240 birds, which were kept for a long-term study, the birds on the H feed were slaughtered at 42 days of age and the ones on the L feed at 49 days of age. The long-term birds were slaughtered at regular intervals, weighed, and necropsied. The last birds were slaughtered at 134 days of age. A large number of skeletal lesions were found. They were: Twisted legs, slipped tendons, crooked toes, bowing of the proximal tibia, dyschondroplasia at different sites, fracture of the fibula, deformity of the spine, deviated sternum (with breast blisters), arthritis, and osteomyelitis. Leg weakness was found to be almost synonymous with skeletal deformities. Other causes were rare. The normal development and morphology of the skeleton and the morphology of tibial dyschondroplasia were the same as those previously described in the turkey. Dyschondroplasia was found not only in the proximal tibia but also in the distal tibia, proximal tarsometatarsus, proximal and distal femur, and to some extent also in the costochondral junction. Tibial dyschondroplasia was more common in the birds on the H feed than in the birds on the L feed. Hence, tibial dyschondroplasia was correlated with rapid growth. The other skeletal lesions did not differ in incidence in the birds on the H and L feeds. It was postulated that greater difference in growth rate is necessary for a demonstration of a possible correlation between skeletal deformities and growth rate.", "contents": "Skeletal lesions in the broiler, with special reference to dyschondroplasia (osteochondrosis). Pathology, frequency and clinical significance in two strains of birds on high and low energy feed. The material consisted of 2,950 broilers of the variety Hybro Compact of two lines. An equal number of birds of both lines were given either a high energy feed (H) or a low energy feed (L), containing all nutrients known to be required by broilers. During the first 3 weeks, H and L starter feeds were given and thereafter H and L finishing feeds. At 21, 35, and 45 days of age, the birds were weighed in groups, and feed conversion calculated. At 21 days of age, the frequency of crooked toes and swollen hocks was registered. Birds were taken from each group for necropsy at regular intervals. Both clinically normal birds and those with locomotor disturbances were selected for necropsy, including radiographic examination. With the exception of 240 birds, which were kept for a long-term study, the birds on the H feed were slaughtered at 42 days of age and the ones on the L feed at 49 days of age. The long-term birds were slaughtered at regular intervals, weighed, and necropsied. The last birds were slaughtered at 134 days of age. A large number of skeletal lesions were found. They were: Twisted legs, slipped tendons, crooked toes, bowing of the proximal tibia, dyschondroplasia at different sites, fracture of the fibula, deformity of the spine, deviated sternum (with breast blisters), arthritis, and osteomyelitis. Leg weakness was found to be almost synonymous with skeletal deformities. Other causes were rare. The normal development and morphology of the skeleton and the morphology of tibial dyschondroplasia were the same as those previously described in the turkey. Dyschondroplasia was found not only in the proximal tibia but also in the distal tibia, proximal tarsometatarsus, proximal and distal femur, and to some extent also in the costochondral junction. Tibial dyschondroplasia was more common in the birds on the H feed than in the birds on the L feed. Hence, tibial dyschondroplasia was correlated with rapid growth. The other skeletal lesions did not differ in incidence in the birds on the H and L feeds. It was postulated that greater difference in growth rate is necessary for a demonstration of a possible correlation between skeletal deformities and growth rate."}
{"id": "PMID:233599", "title": "Pathology of so-called leg weakness in the pig.", "content": "The morphologic background of the poorly defined clinical entity called leg weakness in pigs was determined. Two hundred and thirty skeletons of breeding pigs slaughtered because of leg weakness were studied. Macroscopic, radiologic, bacteriologic and histologic examinations were performed. Three main types of pathologic changes were found and defined: Osteochondrosis, osteoarthrosis and arthritis. Distribution of the changes and their interrelationship were studied as well as age, sex and breed incidence. It was concluded that osteochondrosis is the most important cause of leg weakness. In adolescent animals, manifestations of osteochondrosis were seen in joints and growth plates of almost all individuals. A high frequency of osteoarthrosis, higher with increasing age, was also found. In most animals osteoarthrosis seemed to be secondary to osteochondrosis. However, primary osteoarthrosis of the hock joint similar to spavin in the horse was found. This lesion occurred already in young animals. Chronic proliferative arthritis and discospondylitis were frequent. Suppurative arthritis and osteomyelitis due to pyemia were also common findings. Inflammatory changes were seen as complications to osteochondrosis. Arthritis was secondary to osteochondrosis in importance as the cause of leg weakness in the pig.", "contents": "Pathology of so-called leg weakness in the pig. The morphologic background of the poorly defined clinical entity called leg weakness in pigs was determined. Two hundred and thirty skeletons of breeding pigs slaughtered because of leg weakness were studied. Macroscopic, radiologic, bacteriologic and histologic examinations were performed. Three main types of pathologic changes were found and defined: Osteochondrosis, osteoarthrosis and arthritis. Distribution of the changes and their interrelationship were studied as well as age, sex and breed incidence. It was concluded that osteochondrosis is the most important cause of leg weakness. In adolescent animals, manifestations of osteochondrosis were seen in joints and growth plates of almost all individuals. A high frequency of osteoarthrosis, higher with increasing age, was also found. In most animals osteoarthrosis seemed to be secondary to osteochondrosis. However, primary osteoarthrosis of the hock joint similar to spavin in the horse was found. This lesion occurred already in young animals. Chronic proliferative arthritis and discospondylitis were frequent. Suppurative arthritis and osteomyelitis due to pyemia were also common findings. Inflammatory changes were seen as complications to osteochondrosis. Arthritis was secondary to osteochondrosis in importance as the cause of leg weakness in the pig."}
{"id": "PMID:233600", "title": "Normal and pathologic skeletal development in broiler and leghorn chickens. A comparative investigation.", "content": "Skeletal development of broilers of two lines of the Hybro Compact strain was compared to the skeletal development of leghorns. Environment, management, and feeds were identical for comparable groups of broilers and leghorns. Half of the broilers (representing both lines) and half of the leghorns were given a high energy feed, while the other half of the birds of both breeds were given a low energy feed. No great difference in feed conversion between broilers and leghorns was found. The broilers consumed more feed and increased their body weight and volume of the tibia almost twice as fast as the leghorns. The difference in longitudinal growth of the tibia of the birds of the two breeds was much less evident. Locomotor disturbances (leg weakness) were common in the broilers, and in the majority of the cases the problems were caused by skeletal deformities. The leghorns were almost completely free of skeletal deformities and had no locomotor disturbances. Likewise, dyschondroplasia was not found in the leghorns, while it was common in the broilers. Most of the skeletal deformities in the broilers were explained as the result of mechanic-traumatic factors, acting on a rapidly remodeling skeleton, apparently of insufficient strength for the heavy body weight. Dyschondroplasia, on the other hand, was considered to be caused by a generalized factor governing growth. Basic histologic differences between broilers and leghorns already at an age of 7 days supported this theory. It was concluded that both leg deformities and dyschondroplasia in the broiler are man made problems, caused by genetic selection for characteristics of economic importance, without enough consideration to function and health of the animals.", "contents": "Normal and pathologic skeletal development in broiler and leghorn chickens. A comparative investigation. Skeletal development of broilers of two lines of the Hybro Compact strain was compared to the skeletal development of leghorns. Environment, management, and feeds were identical for comparable groups of broilers and leghorns. Half of the broilers (representing both lines) and half of the leghorns were given a high energy feed, while the other half of the birds of both breeds were given a low energy feed. No great difference in feed conversion between broilers and leghorns was found. The broilers consumed more feed and increased their body weight and volume of the tibia almost twice as fast as the leghorns. The difference in longitudinal growth of the tibia of the birds of the two breeds was much less evident. Locomotor disturbances (leg weakness) were common in the broilers, and in the majority of the cases the problems were caused by skeletal deformities. The leghorns were almost completely free of skeletal deformities and had no locomotor disturbances. Likewise, dyschondroplasia was not found in the leghorns, while it was common in the broilers. Most of the skeletal deformities in the broilers were explained as the result of mechanic-traumatic factors, acting on a rapidly remodeling skeleton, apparently of insufficient strength for the heavy body weight. Dyschondroplasia, on the other hand, was considered to be caused by a generalized factor governing growth. Basic histologic differences between broilers and leghorns already at an age of 7 days supported this theory. It was concluded that both leg deformities and dyschondroplasia in the broiler are man made problems, caused by genetic selection for characteristics of economic importance, without enough consideration to function and health of the animals."}
{"id": "PMID:233602", "title": "Morphology of osteochondrosis and sequelae in pigs.", "content": "The morphologic features of osteochondrosis were studied in skeletons of 176 pigs of different ages. Macroscopic and histologic as well as radiologic and microradiographic methods were used. Osteochondrosis was found to be a generalized disease, characterized by a disturbance of endochondral ossification. It was concluded that early changes occur at about 4 months of age in the growth cartilage. Both the metaphyseal growth cartilage (growth plates) and epiphyseal growth cartilage (joint cartilage) were affected. Abnormal hypertrophy and hyperplasia of cartilage as well as focal degeneration were seen in the early cases. Osteochondrosis was found to lead to abnormal skeletal growth and change in shape of various bones and joints. Serious manifestations of osteochondrosis were epiphyseolysis and osteochondritis dissecans. A quantitative difference was found between different individuals in development of osteochondrosis. The onset of clinical signs was thought to depend on degree and localization of osteochondrosis.", "contents": "Morphology of osteochondrosis and sequelae in pigs. The morphologic features of osteochondrosis were studied in skeletons of 176 pigs of different ages. Macroscopic and histologic as well as radiologic and microradiographic methods were used. Osteochondrosis was found to be a generalized disease, characterized by a disturbance of endochondral ossification. It was concluded that early changes occur at about 4 months of age in the growth cartilage. Both the metaphyseal growth cartilage (growth plates) and epiphyseal growth cartilage (joint cartilage) were affected. Abnormal hypertrophy and hyperplasia of cartilage as well as focal degeneration were seen in the early cases. Osteochondrosis was found to lead to abnormal skeletal growth and change in shape of various bones and joints. Serious manifestations of osteochondrosis were epiphyseolysis and osteochondritis dissecans. A quantitative difference was found between different individuals in development of osteochondrosis. The onset of clinical signs was thought to depend on degree and localization of osteochondrosis."}
{"id": "PMID:233604", "title": "Effects of vitamin D and A, calcium, phosphorus, and protein on frequency and severity of osteochondrosis in pigs.", "content": "The generalized nature of osteochondrosis indicates that systemic factors, i.e. of nutritional or genetic origin, are of importance in etiology of osteochondrosis. Several experimental investigations are reported. On the basis of the morphologic findings it was considered possible that dietary factors such as hypovitaminosis D, hyper- or hypovitaminosis A, and low calcium or high protein intake could be of importance in etiology. The reason for this was that there were similarities between cartilage changes in osteochondrosis and those observed in various dietary imbalances in other domestic animals and in experiments with pigs. The effect of hyper- and hypovitaminosis A and hypovitaminosis D was studied in 23 pigs from 2 litters. In another experiment 32 pigs from 4 litters were fed rations with varying levels of calcium, phosphorus, and protein in the feed. Clinical examinations were made of these animals. Bone seeking fluorochromes were given prior to slaughter, and complete necropsy was performed, including macroscopic, radiologic, histologic and microradiographic techniques. Neither hypervitaminosis A, nor hypovitaminosis A and D had any noticeable effect on frequency and severity of osteochondrosis. A similar negative finding was made in the experiment with different intake of calcium and protein.", "contents": "Effects of vitamin D and A, calcium, phosphorus, and protein on frequency and severity of osteochondrosis in pigs. The generalized nature of osteochondrosis indicates that systemic factors, i.e. of nutritional or genetic origin, are of importance in etiology of osteochondrosis. Several experimental investigations are reported. On the basis of the morphologic findings it was considered possible that dietary factors such as hypovitaminosis D, hyper- or hypovitaminosis A, and low calcium or high protein intake could be of importance in etiology. The reason for this was that there were similarities between cartilage changes in osteochondrosis and those observed in various dietary imbalances in other domestic animals and in experiments with pigs. The effect of hyper- and hypovitaminosis A and hypovitaminosis D was studied in 23 pigs from 2 litters. In another experiment 32 pigs from 4 litters were fed rations with varying levels of calcium, phosphorus, and protein in the feed. Clinical examinations were made of these animals. Bone seeking fluorochromes were given prior to slaughter, and complete necropsy was performed, including macroscopic, radiologic, histologic and microradiographic techniques. Neither hypervitaminosis A, nor hypovitaminosis A and D had any noticeable effect on frequency and severity of osteochondrosis. A similar negative finding was made in the experiment with different intake of calcium and protein."}
{"id": "PMID:233613", "title": "Study of spin-lattice and spin-spin relaxation times of 1H, 2H, and 17O in muscular water.", "content": "Spin-lattice (T1) and spin-spin (T2) relaxation times of proton, deuteron, and oxygen-17 in muscle water have been measured at 9.21 MHz in the temperature range of 0 degree--40 degrees C. The values of the apparent activation energy for the three nuclei are (in kJ . mol-1) 9.1, 19, and 18 for 1/T1, and -1.3, 4.2, and 14 for 1/T2, respectively. The relatively small values for T2 for 1H and 2H and their low apparent activation energies are attributed to hydrogen exchange between water and proteins; this exchange does not affect the 17O relaxation. Quantitative calculations on deuteron T1 and oxygen-17 T1 and T2 have been made. The effect of surface-induced anisotropy on a minor fraction of water molecules is considered in some detail, and a new expression for its spectral density similar to that of liquid crystalline systems is applied in the calculation. It is suggested that water on the surfaces of macromolecules has a rotational correlation time of tau c approximately 1 x 10(-9) S, with a time constant of tau x approximately 3 x 10(-7) S, which is characteristic of the relaxation of the local structure.", "contents": "Study of spin-lattice and spin-spin relaxation times of 1H, 2H, and 17O in muscular water. Spin-lattice (T1) and spin-spin (T2) relaxation times of proton, deuteron, and oxygen-17 in muscle water have been measured at 9.21 MHz in the temperature range of 0 degree--40 degrees C. The values of the apparent activation energy for the three nuclei are (in kJ . mol-1) 9.1, 19, and 18 for 1/T1, and -1.3, 4.2, and 14 for 1/T2, respectively. The relatively small values for T2 for 1H and 2H and their low apparent activation energies are attributed to hydrogen exchange between water and proteins; this exchange does not affect the 17O relaxation. Quantitative calculations on deuteron T1 and oxygen-17 T1 and T2 have been made. The effect of surface-induced anisotropy on a minor fraction of water molecules is considered in some detail, and a new expression for its spectral density similar to that of liquid crystalline systems is applied in the calculation. It is suggested that water on the surfaces of macromolecules has a rotational correlation time of tau c approximately 1 x 10(-9) S, with a time constant of tau x approximately 3 x 10(-7) S, which is characteristic of the relaxation of the local structure."}
{"id": "PMID:233619", "title": "Studies in epidemiology of maedi/visna in sheep.", "content": "Lambs born to ewes from flocks with a high incidence of maedi/visna were separated from their dams at birth (group 1), or after 10 h (group 2), six weeks (group 3) or one year (group 4) and were observed for periods of up to eight years. Group 1 lambs remained free of infection while 28 per cent, 76 per cent and 81 per cent respectively of lambs in the other groups developed clinical, serological or histopathological evidence of infection during the observation period. It is therefore concluded that vertical transmission, if it occurs at all, is of little significance in the epidemiology of the disease. The number of serologically, virologically and histopathologically maedi/visna positive sheep, the time of onset of disease and the severity of lesions were related to the duration of exposure to the parent flock. In a separate trial no evidence was obtained for the transmission of maedi/visna by Muellerius capillaris larvae.", "contents": "Studies in epidemiology of maedi/visna in sheep. Lambs born to ewes from flocks with a high incidence of maedi/visna were separated from their dams at birth (group 1), or after 10 h (group 2), six weeks (group 3) or one year (group 4) and were observed for periods of up to eight years. Group 1 lambs remained free of infection while 28 per cent, 76 per cent and 81 per cent respectively of lambs in the other groups developed clinical, serological or histopathological evidence of infection during the observation period. It is therefore concluded that vertical transmission, if it occurs at all, is of little significance in the epidemiology of the disease. The number of serologically, virologically and histopathologically maedi/visna positive sheep, the time of onset of disease and the severity of lesions were related to the duration of exposure to the parent flock. In a separate trial no evidence was obtained for the transmission of maedi/visna by Muellerius capillaris larvae."}
{"id": "PMID:233632", "title": "Calcium-dependent aldosterone secretion in anephric and nonnephrectomized patients on regular hemodialysis.", "content": "The present study was undertaken to investigate the effect of a continuous calcium infusion on the plasma levels of aldosterone, renin activity, and cortisol in six anephric and four nonnephrectomized patients on regular hemodialysis. In both groups, a significant increase in whole blood ionized calcium (b-Ca2+) was demonstrated. A significant increase in plasma aldosterone (PAC) was noted in the nonnephrectomized patients, in whom the rise in PAC correlated with the increase in b-Ca2+. However, in the anephric patients only a smaller and insignificant increase in PAC was found. No significant changes were demonstrated in plasma cortisol or renin activity, nor in potassium or sodium concentrations in either group. It is concluded that ionized calcium influences the plasma levels of aldosterone in uremic patients on regular hemodialysis.", "contents": "Calcium-dependent aldosterone secretion in anephric and nonnephrectomized patients on regular hemodialysis. The present study was undertaken to investigate the effect of a continuous calcium infusion on the plasma levels of aldosterone, renin activity, and cortisol in six anephric and four nonnephrectomized patients on regular hemodialysis. In both groups, a significant increase in whole blood ionized calcium (b-Ca2+) was demonstrated. A significant increase in plasma aldosterone (PAC) was noted in the nonnephrectomized patients, in whom the rise in PAC correlated with the increase in b-Ca2+. However, in the anephric patients only a smaller and insignificant increase in PAC was found. No significant changes were demonstrated in plasma cortisol or renin activity, nor in potassium or sodium concentrations in either group. It is concluded that ionized calcium influences the plasma levels of aldosterone in uremic patients on regular hemodialysis."}
{"id": "PMID:233633", "title": "Thyrotropin displacement activity of serum immunoglobulins from patients with Graves' disease.", "content": "A radioreceptor assay for human thyroid stimulators has been employed in various groups of patients. The ability of Ig to displace the labeled TSH from the receptors is referred to as \"TSH displacement activity (TDA).\" In active Graves' disease, TDA was above normal in 76% of the cases, and in the remaining patients, it was above the 76th percentile, suggesting that thyroid-stimulating Ig (TSIg) may have been present in all cases, but not always demonstrable by this method. Significant TDA was not found in normal persons or in toxic or nontoxic nodular goiters. It was also negative in some patients with \"euthyroid ophthalmic Graves' disease.\" In patients with Graves' disease controlled with antithyroid drugs, positive TDA accurately predicted the recurrence of hyperthyroidism in eight of nine cases from whom the drugs were withdrawn. Thus, TSIg appears to be a prerequisite of the hyperthyroidism of Graves' disease. Moreover, the remission of hyperthyroidism was due to the disappearance of TSIg (immunological remission) in most cases in this small series. Serum TDA may provide a means of detecting immunological remission. The exophthalmos of Graves' disease does not require thyroid-stimulating Ig.", "contents": "Thyrotropin displacement activity of serum immunoglobulins from patients with Graves' disease. A radioreceptor assay for human thyroid stimulators has been employed in various groups of patients. The ability of Ig to displace the labeled TSH from the receptors is referred to as \"TSH displacement activity (TDA).\" In active Graves' disease, TDA was above normal in 76% of the cases, and in the remaining patients, it was above the 76th percentile, suggesting that thyroid-stimulating Ig (TSIg) may have been present in all cases, but not always demonstrable by this method. Significant TDA was not found in normal persons or in toxic or nontoxic nodular goiters. It was also negative in some patients with \"euthyroid ophthalmic Graves' disease.\" In patients with Graves' disease controlled with antithyroid drugs, positive TDA accurately predicted the recurrence of hyperthyroidism in eight of nine cases from whom the drugs were withdrawn. Thus, TSIg appears to be a prerequisite of the hyperthyroidism of Graves' disease. Moreover, the remission of hyperthyroidism was due to the disappearance of TSIg (immunological remission) in most cases in this small series. Serum TDA may provide a means of detecting immunological remission. The exophthalmos of Graves' disease does not require thyroid-stimulating Ig."}
{"id": "PMID:233634", "title": "An increase of plasma triiodothyronine and thyroxine after administration of dexamethasone to hypothyroid patients with Hashimoto's thyroiditis.", "content": "In an attempt to study the effect of adrenal steroids on plasma thyroid hormone concentration in patients with Hashimoto's thyroiditis, 2 mg dexamethasone was administered for 2-4 weeks to 9 patients with normal plasma TSH, 3 patients with compensatory increase of plasma TSH, and 10 patients with a marked elevation of plasma TSH. Dexamethasone depressed plasma T4, T3, and TSH and reduced thyroid size in nine euthyroid patients, whereas a similar treatment did not affect plasma T3 and T4, but reduced plasma TSH and thyroid size in three patients with compensatory increase of plasma TSH. In contrast, dexamethasone elevated plasma T3 and T4 in 10 hypothyroid patients with a marked elevation of plasma TSH. The increase of T3 was more than that of T4, suggesting preferential secretion of T3. Plasma TSH was reduced, but was still above normal after administration of dexamethasone. It is suggested that the intrathyroidal autoimmune processes inhibiting thyroid hormone synthesis are significant in patients with more severe Hashimoto's thyroiditis, and that dexamethasone stimulated hormone synthesis by depressing the autoimmune processes.", "contents": "An increase of plasma triiodothyronine and thyroxine after administration of dexamethasone to hypothyroid patients with Hashimoto's thyroiditis. In an attempt to study the effect of adrenal steroids on plasma thyroid hormone concentration in patients with Hashimoto's thyroiditis, 2 mg dexamethasone was administered for 2-4 weeks to 9 patients with normal plasma TSH, 3 patients with compensatory increase of plasma TSH, and 10 patients with a marked elevation of plasma TSH. Dexamethasone depressed plasma T4, T3, and TSH and reduced thyroid size in nine euthyroid patients, whereas a similar treatment did not affect plasma T3 and T4, but reduced plasma TSH and thyroid size in three patients with compensatory increase of plasma TSH. In contrast, dexamethasone elevated plasma T3 and T4 in 10 hypothyroid patients with a marked elevation of plasma TSH. The increase of T3 was more than that of T4, suggesting preferential secretion of T3. Plasma TSH was reduced, but was still above normal after administration of dexamethasone. It is suggested that the intrathyroidal autoimmune processes inhibiting thyroid hormone synthesis are significant in patients with more severe Hashimoto's thyroiditis, and that dexamethasone stimulated hormone synthesis by depressing the autoimmune processes."}
{"id": "PMID:233635", "title": "Measurement of plasma adenosine 3',5'-monophosphate.", "content": "Currently used methods for plasma cAMP measurements are either tedious (chromatographic preparation of sample) or potentially inaccurate (direct assay of plasma samples). A rapid, simple, and accurate competitive binding assay for plasma cAMP, which does not require chromatographic preparation of the sample, has been developed. This procedure prevents destruction of plasma cAMP by utilizing both theophylline and EDTA in the collection of the blood sample. Human plasma contains variable amounts of cAMP-binding activity which interfere with the measurement of cAMP by the standard competitive binding assay. Our assay procedure removes this binding activity by precipitation of plasma proteins with perchloric acid. The normal fasting value (+/- SD) of plasma cAMP using this technique is 17.6 +/- 4.3 pmol/ml, which is identical to values obtained by methods utilizing chromatographic purification of samples (18.3 +/- 3.0). The fasting plasma cAMP of patients with hyperparathyroidism is normal (16.2 +/- 3.4), but patients with maturity-onset diabetes mellitus have fasting values significantly below normal (12.3 +/- 2.4).", "contents": "Measurement of plasma adenosine 3',5'-monophosphate. Currently used methods for plasma cAMP measurements are either tedious (chromatographic preparation of sample) or potentially inaccurate (direct assay of plasma samples). A rapid, simple, and accurate competitive binding assay for plasma cAMP, which does not require chromatographic preparation of the sample, has been developed. This procedure prevents destruction of plasma cAMP by utilizing both theophylline and EDTA in the collection of the blood sample. Human plasma contains variable amounts of cAMP-binding activity which interfere with the measurement of cAMP by the standard competitive binding assay. Our assay procedure removes this binding activity by precipitation of plasma proteins with perchloric acid. The normal fasting value (+/- SD) of plasma cAMP using this technique is 17.6 +/- 4.3 pmol/ml, which is identical to values obtained by methods utilizing chromatographic purification of samples (18.3 +/- 3.0). The fasting plasma cAMP of patients with hyperparathyroidism is normal (16.2 +/- 3.4), but patients with maturity-onset diabetes mellitus have fasting values significantly below normal (12.3 +/- 2.4)."}
{"id": "PMID:233636", "title": "Immunoreactive endorphins, lipotropins and corticotropins in a human nonpituitary tumor: evidence for a common precursor.", "content": "The immunoreactive (RIA), ACTH, LPH, alpha endorphin (alpha End) and beta End in an extract of a human pancreatic islet cell carcinoma causing the ectopic ACTH syndrome were assayed after gel exclusion chromatography. In addition to \"big\", \"intermediate\" and \"little\" ACTHs, beta lipotropin (beta LPH) and gamma LPH, the eluate fractions contained RIA-alpha End and -beta End. The major RIA-beta End component appeared to be h beta LPH, which has beta End as its carboxy-terminus, but significant concentrations of a component that coeluted with synthetic p beta End were also found. Small amounts of RIA-alpha End were found in two peaks, one that may have represented 1-76 h beta LPH, with alpha End as its carboxy-terminus, and one probably representing alpha End itself. RIA-ACTH, -LPH and -beta End were found in the void volume fractions. Thus, a human nonpituitary tumor that produced ACTH and LPHs also produced endorphins, all perhaps deriving from a common precursor.", "contents": "Immunoreactive endorphins, lipotropins and corticotropins in a human nonpituitary tumor: evidence for a common precursor. The immunoreactive (RIA), ACTH, LPH, alpha endorphin (alpha End) and beta End in an extract of a human pancreatic islet cell carcinoma causing the ectopic ACTH syndrome were assayed after gel exclusion chromatography. In addition to \"big\", \"intermediate\" and \"little\" ACTHs, beta lipotropin (beta LPH) and gamma LPH, the eluate fractions contained RIA-alpha End and -beta End. The major RIA-beta End component appeared to be h beta LPH, which has beta End as its carboxy-terminus, but significant concentrations of a component that coeluted with synthetic p beta End were also found. Small amounts of RIA-alpha End were found in two peaks, one that may have represented 1-76 h beta LPH, with alpha End as its carboxy-terminus, and one probably representing alpha End itself. RIA-ACTH, -LPH and -beta End were found in the void volume fractions. Thus, a human nonpituitary tumor that produced ACTH and LPHs also produced endorphins, all perhaps deriving from a common precursor."}
{"id": "PMID:233637", "title": "Proposed metabolic dysfunctions in diabetic microthromboses and microangiopathy.", "content": "This report describes, at least in part, the role of prostaglandin and cyclic nucleotide metabolism in the etiology of the vascular disease associated with diabetes mellitus. Alterations in this metabolism seem associated with induction of platelet aggregation leads to microthromboses leads to microangiopathy sequences that are subtle but inexorable over a long period of time. Prostaglandins are generally elevated in blood from patients having frank signs of diabetic retinopathy when compared with nondiabetic subjects. Prostaglandin concentration remained elevated in diabetic retinopathy patients receiving indomethacin. We formed, therefore, the working hypothesis--yet to be fully tested either in patients or animal models with and without indomethacin treatment--that the increased prostacyclin (synthesized by endothelial microsomes) and cyclic-AMP production, both of which favor prevention of platelet aggregation, accompany the increased concentration of one or more of the prostaglandin E and F compounds. Concurrently, there may be an accompanying reduction of thromboxane A2 (synthesized by platelet microsomes) and cyclic-GMP (both of which favor platelet aggregation) production in the diabetic patients. The elevated prostaglandin in the diabetic patients not receiving indomethacin could possibly be directed toward slowing but not preventing the progression of the complex disease process in diabetes.", "contents": "Proposed metabolic dysfunctions in diabetic microthromboses and microangiopathy. This report describes, at least in part, the role of prostaglandin and cyclic nucleotide metabolism in the etiology of the vascular disease associated with diabetes mellitus. Alterations in this metabolism seem associated with induction of platelet aggregation leads to microthromboses leads to microangiopathy sequences that are subtle but inexorable over a long period of time. Prostaglandins are generally elevated in blood from patients having frank signs of diabetic retinopathy when compared with nondiabetic subjects. Prostaglandin concentration remained elevated in diabetic retinopathy patients receiving indomethacin. We formed, therefore, the working hypothesis--yet to be fully tested either in patients or animal models with and without indomethacin treatment--that the increased prostacyclin (synthesized by endothelial microsomes) and cyclic-AMP production, both of which favor prevention of platelet aggregation, accompany the increased concentration of one or more of the prostaglandin E and F compounds. Concurrently, there may be an accompanying reduction of thromboxane A2 (synthesized by platelet microsomes) and cyclic-GMP (both of which favor platelet aggregation) production in the diabetic patients. The elevated prostaglandin in the diabetic patients not receiving indomethacin could possibly be directed toward slowing but not preventing the progression of the complex disease process in diabetes."}
{"id": "PMID:233639", "title": "Serum angiotensin--converting enzyme (SACE) in sarcoidosis and other granulomatous disorders.", "content": "Serum angiotensin-converting enzyme (SACE) activity was significantly higher in 90 patients with sarcoidosis (55 +/- [S.D.] 23 nmol min-1 ml-1) than in 80 healthy controls (34 +/- 9 nmol min-1 ml-1). Steroid therapy modified SACE activity; 60 sarcoidosis patients who were not being treated with steroids had significantly higher enzyme activities (58 +/- 24 nmol min-1 ml-1) than 30 steroid-treated sarcoidosis patients (40 +/- 19 nmol min-1 ml-1). In 50% of the non-steroid treated sarcoidosis patients SACE activity was more than than 2 S.D. above the mean value for the controls. SACE activity was measured in 22 tuberculous patients (38 +/- 14 nmol min-1 ml-1), 20 leprosy patients (34 +/- 9 nmol min-1 ml-1), 31 with primary biliary cirrhosis (44 +/- 20 nmol min-1 ml-1), 26 with inflammatory bowel disease (31 +/- 9 nmol min-1 ml-1), eight with hepatic granulomatous disease, five with Hodgkin's disease, and two with schistosomiasis. The combined false-positive rate for these non-sarcoidosis patients was 10%. Serial SACE assays provide useful information on the course of sarcoidosis and response to steroid treatment.", "contents": "Serum angiotensin--converting enzyme (SACE) in sarcoidosis and other granulomatous disorders. Serum angiotensin-converting enzyme (SACE) activity was significantly higher in 90 patients with sarcoidosis (55 +/- [S.D.] 23 nmol min-1 ml-1) than in 80 healthy controls (34 +/- 9 nmol min-1 ml-1). Steroid therapy modified SACE activity; 60 sarcoidosis patients who were not being treated with steroids had significantly higher enzyme activities (58 +/- 24 nmol min-1 ml-1) than 30 steroid-treated sarcoidosis patients (40 +/- 19 nmol min-1 ml-1). In 50% of the non-steroid treated sarcoidosis patients SACE activity was more than than 2 S.D. above the mean value for the controls. SACE activity was measured in 22 tuberculous patients (38 +/- 14 nmol min-1 ml-1), 20 leprosy patients (34 +/- 9 nmol min-1 ml-1), 31 with primary biliary cirrhosis (44 +/- 20 nmol min-1 ml-1), 26 with inflammatory bowel disease (31 +/- 9 nmol min-1 ml-1), eight with hepatic granulomatous disease, five with Hodgkin's disease, and two with schistosomiasis. The combined false-positive rate for these non-sarcoidosis patients was 10%. Serial SACE assays provide useful information on the course of sarcoidosis and response to steroid treatment."}
{"id": "PMID:233653", "title": "EEG sleep in primary depression. A longitudinal placebo study.", "content": "Characteristic EEG sleep changes in depression are highlighted by a sleep continuity disturbance, delta sleep reduction, and a shortened REM latency. Since these findings have been derived primarily from only a few baseline recordings, questions regarding their persistence and/or variability have not been previously addressed. As part of an extensive set of investigations of EEG sleep in depression, we examined nightly the sleep of 12 hospitalized, non-delusional, primary depressives who were involved in a program of active psychosocial treatment intervention and received only placebo during a 5-week study period. EEG sleep findings revealed a relative lack of change across time, particularly in those parameters reported to be associated with a primary or 'biologic' depressive episode. While some degree of clinical improvement was noted, the group failed to achieve a state of remission or even partial remission as determined by the Hamilton Rating Scale. It appears that the major sleep alterations associated with such disorders persist for up to at least 5 weeks in the absence of pharmacologic or other somatic intervention.", "contents": "EEG sleep in primary depression. A longitudinal placebo study. Characteristic EEG sleep changes in depression are highlighted by a sleep continuity disturbance, delta sleep reduction, and a shortened REM latency. Since these findings have been derived primarily from only a few baseline recordings, questions regarding their persistence and/or variability have not been previously addressed. As part of an extensive set of investigations of EEG sleep in depression, we examined nightly the sleep of 12 hospitalized, non-delusional, primary depressives who were involved in a program of active psychosocial treatment intervention and received only placebo during a 5-week study period. EEG sleep findings revealed a relative lack of change across time, particularly in those parameters reported to be associated with a primary or 'biologic' depressive episode. While some degree of clinical improvement was noted, the group failed to achieve a state of remission or even partial remission as determined by the Hamilton Rating Scale. It appears that the major sleep alterations associated with such disorders persist for up to at least 5 weeks in the absence of pharmacologic or other somatic intervention."}
{"id": "PMID:233654", "title": "Cystosarcoma phyllodes: a clinicopathological analysis of 14 cases.", "content": "Experience with 14 cases of cystosarcoma phyllodes encountered at the 2nd Department of Propedeutic Surgery, Athens, University, between October, 1928 and December, 1978 is reported. Local excision including a wide cuff of uninvolved breast tissue is indicated for histologically proven benign and small tumors. For bulky or malignant tumors, a simple mastectomy is indicated. none of these neoplasms had metastasized to the axillary lymph nodes and, for this reason, and axillary node dissection was contraindicated.", "contents": "Cystosarcoma phyllodes: a clinicopathological analysis of 14 cases. Experience with 14 cases of cystosarcoma phyllodes encountered at the 2nd Department of Propedeutic Surgery, Athens, University, between October, 1928 and December, 1978 is reported. Local excision including a wide cuff of uninvolved breast tissue is indicated for histologically proven benign and small tumors. For bulky or malignant tumors, a simple mastectomy is indicated. none of these neoplasms had metastasized to the axillary lymph nodes and, for this reason, and axillary node dissection was contraindicated."}
{"id": "PMID:233659", "title": "Effect of oral glucose ingestion on renal phosphate reabsorption and clearance in vitamin D-resistant rickets.", "content": "The effect or oral glucose ingestion on renal phosphate reabsorption was studied in 13 patients with the inherited form of vitamin D-resistant rickets (VDRR) and 5 normal subjects. In contrast to the normal subjects, glycosuria developed in six VDRR patients after glucose ingestion and resulted in a further 43% decrease in renal phosphate reabsorption. This was accompanied by a 33% increase in phosphate clearance. This was not attended by differences in fasting glucose or phosphorus levels between groups, or in their respective values 1 h after glucose ingestion. Baseline renal phosphate reabsorption was less and baseline phosphate clearance was greater in those VDRR subjects who developed glycosuria. The accumulated data suggest that excessive glucose ingestion by some patients with VDRR may add an additional insult to the phosphaturia characteristic of this disorder. This, in turn, would further compromise the response of circulating phosphate to therapeutic attempts at oral phosphate supplementation, thereby reducing the efficacy of oral phosphate therapy on skeletal growth and development in this disorder.", "contents": "Effect of oral glucose ingestion on renal phosphate reabsorption and clearance in vitamin D-resistant rickets. The effect or oral glucose ingestion on renal phosphate reabsorption was studied in 13 patients with the inherited form of vitamin D-resistant rickets (VDRR) and 5 normal subjects. In contrast to the normal subjects, glycosuria developed in six VDRR patients after glucose ingestion and resulted in a further 43% decrease in renal phosphate reabsorption. This was accompanied by a 33% increase in phosphate clearance. This was not attended by differences in fasting glucose or phosphorus levels between groups, or in their respective values 1 h after glucose ingestion. Baseline renal phosphate reabsorption was less and baseline phosphate clearance was greater in those VDRR subjects who developed glycosuria. The accumulated data suggest that excessive glucose ingestion by some patients with VDRR may add an additional insult to the phosphaturia characteristic of this disorder. This, in turn, would further compromise the response of circulating phosphate to therapeutic attempts at oral phosphate supplementation, thereby reducing the efficacy of oral phosphate therapy on skeletal growth and development in this disorder."}
{"id": "PMID:233660", "title": "Effect of parathyroid hormone on plasma prolactin in man.", "content": "The iv infusion of parathyroid extract or the synthetic fragments of 1-34 bovine or human parathyroid hormone produced a rapid and marked increase of plasma PRL in normal subjects. The stimulation of the release of endogenous parathyroid hormone by administration of disodium EDTA also resulted in a parallel increase of plasma PRL. Parathyroid hormone did not act via plasma cAMP, as the plasma level reached by this nucleotide was too small to produce PRL release. The ingestion of L-dopa 2 h before parathyroid hormone infusion suppressed the PRL response, suggesting that dopamine and parathyroid hormone interact at a common site. As it has been recently shown that PRL stimulates the renal synthesis of 1,25-dihydroxycholecalciferol, the present data suggest that the effect of parathyroid hormone on this synthesis may be due to the increase in plasma PRL.", "contents": "Effect of parathyroid hormone on plasma prolactin in man. The iv infusion of parathyroid extract or the synthetic fragments of 1-34 bovine or human parathyroid hormone produced a rapid and marked increase of plasma PRL in normal subjects. The stimulation of the release of endogenous parathyroid hormone by administration of disodium EDTA also resulted in a parallel increase of plasma PRL. Parathyroid hormone did not act via plasma cAMP, as the plasma level reached by this nucleotide was too small to produce PRL release. The ingestion of L-dopa 2 h before parathyroid hormone infusion suppressed the PRL response, suggesting that dopamine and parathyroid hormone interact at a common site. As it has been recently shown that PRL stimulates the renal synthesis of 1,25-dihydroxycholecalciferol, the present data suggest that the effect of parathyroid hormone on this synthesis may be due to the increase in plasma PRL."}
{"id": "PMID:233661", "title": "Comparison of the corticotropic action of two synthetic, substituted analogues of ACTH: ACTH1--17 and ACTH1--18.", "content": "The effect of a recently synthesized analogue of ACTH, Ala1, lys17-ACTH(1-17-4-amino-n-butylamide; (ACTH1-17) upon serum cortisol levels in 9 healthy males was compared with that of ACTH1-18, D-ser1-lys17, 18-ACTH(1-18). Both compounds induced an identical rise in serum cortisol which lasted for at least 8 hours. It is concluded that the amino acid in position 18 is not essential for the corticotropic properties of the synthetic heptadecapeptide. The prolonged effect of these compounds indicates a potential therapeutic significance for ACTH analogues of low molecular weight.", "contents": "Comparison of the corticotropic action of two synthetic, substituted analogues of ACTH: ACTH1--17 and ACTH1--18. The effect of a recently synthesized analogue of ACTH, Ala1, lys17-ACTH(1-17-4-amino-n-butylamide; (ACTH1-17) upon serum cortisol levels in 9 healthy males was compared with that of ACTH1-18, D-ser1-lys17, 18-ACTH(1-18). Both compounds induced an identical rise in serum cortisol which lasted for at least 8 hours. It is concluded that the amino acid in position 18 is not essential for the corticotropic properties of the synthetic heptadecapeptide. The prolonged effect of these compounds indicates a potential therapeutic significance for ACTH analogues of low molecular weight."}
{"id": "PMID:233662", "title": "Regulation of the synthesis of human chorionic gonadotrophin by 5-bromo-2'-deoxyuridine and dibutyryl cyclic AMP in trophoblastic and nontrophoblastic tumor cells.", "content": "Synthesis of hCG and its alpha subunit (hCG-alpha) by trophoblastic tumor cell lines (JEG-3, Reid, and BeWo) and by nontrophoblastic tumor cell lines [ChaGo and three HeLa lines (HeLa CCL2, HeLa S3, and HeLa 65)] was studied. cAMP, dibutyryl cAMP, and 8-bromo-cAMP induced, but 5-bromo-2'-deoxyuridine inhibited, the synthesis of hCG-alpha and hCG in trophoblastic tumor cells, Addition of 5-bromo-2'-deoxyuridine partially blocked the induction by dibutyryl cAMP in these cells. The synthesis of hCG-alpha and hCG in nontrophoblastic tumor cells was stimulated by dibutyryl cAMP. cAMP and 8-bromo-cAMP, however, did not affect the synthesis of hCG-alpha, although the synthesis of hCG was enhanced. 5-Bromo-2'-deoxyuridine induced hCG-alpha synthesis but did not affect hCG synthesis in nontrophoblastic tumor cells. In HeLa S3 and HeLa 65 cells, the amount of hCG-alpha and hCG produced in the presence of dibutyryl cAMP and 5-bromo-2'-deoxyuridine together was greater than the total hormone produced by each inducer separately. Our data indicate that the regulation of the production of hCG-alpha and hCG differs in trophoblastic and nontrophoblastic tumors.", "contents": "Regulation of the synthesis of human chorionic gonadotrophin by 5-bromo-2'-deoxyuridine and dibutyryl cyclic AMP in trophoblastic and nontrophoblastic tumor cells. Synthesis of hCG and its alpha subunit (hCG-alpha) by trophoblastic tumor cell lines (JEG-3, Reid, and BeWo) and by nontrophoblastic tumor cell lines [ChaGo and three HeLa lines (HeLa CCL2, HeLa S3, and HeLa 65)] was studied. cAMP, dibutyryl cAMP, and 8-bromo-cAMP induced, but 5-bromo-2'-deoxyuridine inhibited, the synthesis of hCG-alpha and hCG in trophoblastic tumor cells, Addition of 5-bromo-2'-deoxyuridine partially blocked the induction by dibutyryl cAMP in these cells. The synthesis of hCG-alpha and hCG in nontrophoblastic tumor cells was stimulated by dibutyryl cAMP. cAMP and 8-bromo-cAMP, however, did not affect the synthesis of hCG-alpha, although the synthesis of hCG was enhanced. 5-Bromo-2'-deoxyuridine induced hCG-alpha synthesis but did not affect hCG synthesis in nontrophoblastic tumor cells. In HeLa S3 and HeLa 65 cells, the amount of hCG-alpha and hCG produced in the presence of dibutyryl cAMP and 5-bromo-2'-deoxyuridine together was greater than the total hormone produced by each inducer separately. Our data indicate that the regulation of the production of hCG-alpha and hCG differs in trophoblastic and nontrophoblastic tumors."}
{"id": "PMID:233663", "title": "Isolated deficiency of adrenocorticotropin (ACTH) and lipotropins (LPHs).", "content": "A patient with hypoadrenocorticism was found to have low basal plasma concentrations of ACTH and lipotropins and deficient responses of these hormones to insulin-induced hypoglycemia and lysine vasopressin. The adequacy of secretion of other anterior pituitary hormones was assessed either directly, by measuring their concentration in plasma, or indirectly, by assessing end organ function, under basal and stimulated conditions. The responses of gonadotropins to LRH and of PRL and TSH to TRH were normal. The etiology of this rare condition of isolated deficiency of ACTH and lipotropins remains to be elucidated.", "contents": "Isolated deficiency of adrenocorticotropin (ACTH) and lipotropins (LPHs). A patient with hypoadrenocorticism was found to have low basal plasma concentrations of ACTH and lipotropins and deficient responses of these hormones to insulin-induced hypoglycemia and lysine vasopressin. The adequacy of secretion of other anterior pituitary hormones was assessed either directly, by measuring their concentration in plasma, or indirectly, by assessing end organ function, under basal and stimulated conditions. The responses of gonadotropins to LRH and of PRL and TSH to TRH were normal. The etiology of this rare condition of isolated deficiency of ACTH and lipotropins remains to be elucidated."}
{"id": "PMID:233665", "title": "Reliability of the 30-minute ACTH test in assessing hypothalamic-pituitary-adrenal function.", "content": "An insulin hypoglycemia test and a 30-min ACTH test were performed in 90 patients with proved or suspected hypothalamic-pituitary-adrenal hypofunction and in 10 normal subjects. The peak plasma cortisol concentration during hypoglycemia and the cortisol concentration at 30 min after injection of 250 micrograms corticotropin 1-24 were compared. A very close correlation (r = 0.92) was found between the the two concentrations, with no major discrepancy in any case. It is concluded that the short ACTH test accurately reflects the integrated hypothalamic-pituitary-adrenal function, as assessed by the insulin hypoglycemia test.", "contents": "Reliability of the 30-minute ACTH test in assessing hypothalamic-pituitary-adrenal function. An insulin hypoglycemia test and a 30-min ACTH test were performed in 90 patients with proved or suspected hypothalamic-pituitary-adrenal hypofunction and in 10 normal subjects. The peak plasma cortisol concentration during hypoglycemia and the cortisol concentration at 30 min after injection of 250 micrograms corticotropin 1-24 were compared. A very close correlation (r = 0.92) was found between the the two concentrations, with no major discrepancy in any case. It is concluded that the short ACTH test accurately reflects the integrated hypothalamic-pituitary-adrenal function, as assessed by the insulin hypoglycemia test."}
{"id": "PMID:233664", "title": "ACTH-secreting medullary carcinoma of the thyroid presenting a severe idiopathic osteoporosis and senile purpura: report of a case and review of the literature.", "content": "A 64-yr-old female presented with severe osteoporosis and easy bruisability of over 2-yr duration. Biopsy of a neck mass revealed medullary carcinoma of the thyroid. Subsequently, lymphangitic pulmonary metastases were demonstrated which had been present radiographically for at least 4 yr. Basal serum calcitonin was markedly elevated and increased during calcium infusion. The diagnosis of ectopic ACTH syndrome was first entertained when hypokalemic alkalosis was observed during evaluation of her carcinoma. Elevated urinary 17-hydroxycorticosteroids, 17-ketosteroids, plasma cortisol, and immunoreactive plasma ACTH levels were documented. Adrenal steroidogenesis seemed to suppress on high dose dexamethasone. The primary tumor and its metastases contained high concentrations of immunoreactive ACTH and beta-melanocyte-stimulating hormone. Hepatic metastases contained extremely high concentrations of calcitonin. In contrast to the usual presentation of the ectopic ACTH syndrome as primarily hypokalemic alkalosis and glucose intolerance, patients with relatively benign and indolent ACTH-secreting tumors, such as certain cases of medullary carcinoma of the thyroid, may present with more typical signs and symptoms of Cushing's syndrome. The more pronounced cushingoid features in this latter group presumably reflects a more prolonged period of exposure to elevated glucocorticoid levels. Ten cases of ACTH-secreting medullary carcinoma of the thyroid from the literature are discussed. Extopic ACTH production by such tumors should be considered in the evaluation of patients with Cushing's syndrome or unexplained severe osteopenia.", "contents": "ACTH-secreting medullary carcinoma of the thyroid presenting a severe idiopathic osteoporosis and senile purpura: report of a case and review of the literature. A 64-yr-old female presented with severe osteoporosis and easy bruisability of over 2-yr duration. Biopsy of a neck mass revealed medullary carcinoma of the thyroid. Subsequently, lymphangitic pulmonary metastases were demonstrated which had been present radiographically for at least 4 yr. Basal serum calcitonin was markedly elevated and increased during calcium infusion. The diagnosis of ectopic ACTH syndrome was first entertained when hypokalemic alkalosis was observed during evaluation of her carcinoma. Elevated urinary 17-hydroxycorticosteroids, 17-ketosteroids, plasma cortisol, and immunoreactive plasma ACTH levels were documented. Adrenal steroidogenesis seemed to suppress on high dose dexamethasone. The primary tumor and its metastases contained high concentrations of immunoreactive ACTH and beta-melanocyte-stimulating hormone. Hepatic metastases contained extremely high concentrations of calcitonin. In contrast to the usual presentation of the ectopic ACTH syndrome as primarily hypokalemic alkalosis and glucose intolerance, patients with relatively benign and indolent ACTH-secreting tumors, such as certain cases of medullary carcinoma of the thyroid, may present with more typical signs and symptoms of Cushing's syndrome. The more pronounced cushingoid features in this latter group presumably reflects a more prolonged period of exposure to elevated glucocorticoid levels. Ten cases of ACTH-secreting medullary carcinoma of the thyroid from the literature are discussed. Extopic ACTH production by such tumors should be considered in the evaluation of patients with Cushing's syndrome or unexplained severe osteopenia."}
{"id": "PMID:233666", "title": "A virilizing adrenocortical tumor in a female infant: in vivo and in vitro biochemical characteristics.", "content": "Normal adrenal and adrenal tumor cells from a female infant with a virilizing adrenal tumor were grown in tissue culture as monolayers for a period of 7 weeks. Half of the cultures were exposed to ACTH (0.1 U/ml). The cells grew well and continued to produce steroid hormones over the entire period in culture. Production of steroid hormones was measured by RIA of individual steroids in the culture medium. Unstimulated normal and tumor cells produced equivalent amounts of cortisol, 11 beta, 18, 21-trihydroxy-4-pregnene-3,20-dione, and 18,21-dihydroxy-4-pregnene-3,20-dione, but tumor cells produced lesser amounts of dehydroepiandrosterone (DHA), androstenedione, testosterone, and progesterone. Normal cells exposed to ACTH showed an increase in all steroids measured, whereas ACTH-exposed tumor cells showed an increase principally in DHA consistent with a deficiency in 3 beta-hydroxysteroid dehydrogenase activity. Circulating levels of DHA, androstenedione, and testosterone were elevated in the patient before removal of the adrenal tumor. The production of androgens by tumor cells in vitro resembled the pattern of circulating steroids in vivo. These studies demonstrate that tissue culture of human adrenal cells provides a means both to determine their biochemical characteristics and to investigate their responses to exogenous hormones.", "contents": "A virilizing adrenocortical tumor in a female infant: in vivo and in vitro biochemical characteristics. Normal adrenal and adrenal tumor cells from a female infant with a virilizing adrenal tumor were grown in tissue culture as monolayers for a period of 7 weeks. Half of the cultures were exposed to ACTH (0.1 U/ml). The cells grew well and continued to produce steroid hormones over the entire period in culture. Production of steroid hormones was measured by RIA of individual steroids in the culture medium. Unstimulated normal and tumor cells produced equivalent amounts of cortisol, 11 beta, 18, 21-trihydroxy-4-pregnene-3,20-dione, and 18,21-dihydroxy-4-pregnene-3,20-dione, but tumor cells produced lesser amounts of dehydroepiandrosterone (DHA), androstenedione, testosterone, and progesterone. Normal cells exposed to ACTH showed an increase in all steroids measured, whereas ACTH-exposed tumor cells showed an increase principally in DHA consistent with a deficiency in 3 beta-hydroxysteroid dehydrogenase activity. Circulating levels of DHA, androstenedione, and testosterone were elevated in the patient before removal of the adrenal tumor. The production of androgens by tumor cells in vitro resembled the pattern of circulating steroids in vivo. These studies demonstrate that tissue culture of human adrenal cells provides a means both to determine their biochemical characteristics and to investigate their responses to exogenous hormones."}
{"id": "PMID:233668", "title": "Relationship between thyroid status and Graves' disease-specific immunoglobulins.", "content": "The prevalence of TSI in Graves' disease was investigated with a radioligand receptor assay using human thyroid membranes and highly purified labeled porcine TSH or bovine TSH in 110 patients before treatment and in 39 patients after successful treatment with antithyroid drugs. In 11 patients, the assay was performed before, during, and after therapy. The results in the radioligand receptor assay were compared to thyroid function tests (TRH test, free T4 index, serum %3 level, and thyroid suppression test). Normal IgG inhibits nonspecifically, but dose dependently, the binding of [125I]TSH to thyroid membranes. IgG samples from patients were only considered to be positive if they reduced the binding of the labeled hormone below the mean value minus 2 SD of the controls. TSI activity was found in 50% of the patients with untreated diffuse toxic goiter, in 3 out of 27 cases who regained suppressible thyroid function, and in 5 out of 12 cases who were off therapy for more than 6 weeks and showed normal TRH tests and normal hormone levels but in whom the suppression test was not performed. Our data cannot prove the hypothesis that only humoral antibodies are responsible for the thyroid stimulation in Graves' disease, but of course they cannot exclude it; furthermore, they suggest the existence of antibodies which bind to the human thyroid cell membrane without necessarily stimulating thyroid cellular activity.", "contents": "Relationship between thyroid status and Graves' disease-specific immunoglobulins. The prevalence of TSI in Graves' disease was investigated with a radioligand receptor assay using human thyroid membranes and highly purified labeled porcine TSH or bovine TSH in 110 patients before treatment and in 39 patients after successful treatment with antithyroid drugs. In 11 patients, the assay was performed before, during, and after therapy. The results in the radioligand receptor assay were compared to thyroid function tests (TRH test, free T4 index, serum %3 level, and thyroid suppression test). Normal IgG inhibits nonspecifically, but dose dependently, the binding of [125I]TSH to thyroid membranes. IgG samples from patients were only considered to be positive if they reduced the binding of the labeled hormone below the mean value minus 2 SD of the controls. TSI activity was found in 50% of the patients with untreated diffuse toxic goiter, in 3 out of 27 cases who regained suppressible thyroid function, and in 5 out of 12 cases who were off therapy for more than 6 weeks and showed normal TRH tests and normal hormone levels but in whom the suppression test was not performed. Our data cannot prove the hypothesis that only humoral antibodies are responsible for the thyroid stimulation in Graves' disease, but of course they cannot exclude it; furthermore, they suggest the existence of antibodies which bind to the human thyroid cell membrane without necessarily stimulating thyroid cellular activity."}
{"id": "PMID:233669", "title": "Licorice raises urinary cortisol in man.", "content": "The finding that urine cortisol excretion was increased in patients with hypokalaemic hypertension induced by licorice addiction led to this study on the effect of licorice in normal subjects. Thirteen normal volunteers ate either 100 or 200 g licorice for 1-4 weeks and assessment of pituitary-adrenal function was made before, during, and 1 week after cessation of licorice ingestion. Urine cortisol excretion more than doubled in 10 of 13 subjects (mean, 33.8 +/- 15.6 SD before and 83.3 +/- 56 SD micrograms/24 h at 1 week after commencing licorice) and excretion rates similar to those observed in Cushing's syndrome were seen in 7 subjects (range, 91-226, compared to normal range of 11-82 micrograms/24 h). Urine cortisol excretion remained significantly elevated (P less than 0.01) above control levels for at least 1 week after licorice was withdrawn. Despite these increases, urinary steroid metabolite (tetrahydrocortisol, tetrahydrocortisone, tetrahydro-11-deoxycortisol, 17-ketogenicsteroids, and 17-ketosteroids) excretion was not affected, plasma cortisol and ACTH values were unchanged, and normal 0800-1600-h diurnal variation of plasma cortisol was maintained. The direct intraadrenal infusion of the active mineralocorticoid component of licorice, glycyrrhetinic acid, in two sheep with autotransplanted adrenal glands failed to stimulate cortisol secretion acutely. It is concluded from these studies that the licorice-induced changes in cortisol excretion are not a result of adrenocoritcal stimulation but more likely represent a change in the renal handling of cortisol.", "contents": "Licorice raises urinary cortisol in man. The finding that urine cortisol excretion was increased in patients with hypokalaemic hypertension induced by licorice addiction led to this study on the effect of licorice in normal subjects. Thirteen normal volunteers ate either 100 or 200 g licorice for 1-4 weeks and assessment of pituitary-adrenal function was made before, during, and 1 week after cessation of licorice ingestion. Urine cortisol excretion more than doubled in 10 of 13 subjects (mean, 33.8 +/- 15.6 SD before and 83.3 +/- 56 SD micrograms/24 h at 1 week after commencing licorice) and excretion rates similar to those observed in Cushing's syndrome were seen in 7 subjects (range, 91-226, compared to normal range of 11-82 micrograms/24 h). Urine cortisol excretion remained significantly elevated (P less than 0.01) above control levels for at least 1 week after licorice was withdrawn. Despite these increases, urinary steroid metabolite (tetrahydrocortisol, tetrahydrocortisone, tetrahydro-11-deoxycortisol, 17-ketogenicsteroids, and 17-ketosteroids) excretion was not affected, plasma cortisol and ACTH values were unchanged, and normal 0800-1600-h diurnal variation of plasma cortisol was maintained. The direct intraadrenal infusion of the active mineralocorticoid component of licorice, glycyrrhetinic acid, in two sheep with autotransplanted adrenal glands failed to stimulate cortisol secretion acutely. It is concluded from these studies that the licorice-induced changes in cortisol excretion are not a result of adrenocoritcal stimulation but more likely represent a change in the renal handling of cortisol."}
{"id": "PMID:233670", "title": "Role of angiotensin II in the aldosterone secretory response to adrenocorticotropin in sodium-restricted normal human subjects.", "content": "A study was performed to determine the possible role of angiotensin II (AII) in mediating the increased adrenal aldosterone response to infused alpha 1-24-ACTH, induced by sodium deprivation. Nine normal subjects, aged 18-31 yr. received 8-h infusions of 1) alpha 1-24-ACTH (0.5 U given over 8 h) while on a diet with unrestricted sodium content; 2) saralasin at 0.5 micrograms/kg/min or ACTH alone (0.5 U over 8 h) on the 7th day of a 10 meq sodium diet; and 3) ACTH and saralasin together on the 8th day while still on sodium restriction. AII was administered for the last 2 h of infusion 3. Plasma cortisol and aldosterone concentrations were measured at hourly intervals during the infusions and plasma renin activity was measured at 2 hourly intervals. ACTH infusion produced an increase in the plasma aldosterone concentration which was significantly greater during sodium restriction than when sodium intake was unlimited. This increase was not associated with an ACTH-induced rise in the plasma renin activity and was not significantly altered when ACTH was administered with saralasin. The rise in plasma cortisol concentration induced by ACTH was not significantly different when the normal subjects were on liberal and restricted sodium intakes. It is concluded that AII plays little if any acute role in increasing the stimulatory action of ACTH on aldosterone secretion during sodium restriction.", "contents": "Role of angiotensin II in the aldosterone secretory response to adrenocorticotropin in sodium-restricted normal human subjects. A study was performed to determine the possible role of angiotensin II (AII) in mediating the increased adrenal aldosterone response to infused alpha 1-24-ACTH, induced by sodium deprivation. Nine normal subjects, aged 18-31 yr. received 8-h infusions of 1) alpha 1-24-ACTH (0.5 U given over 8 h) while on a diet with unrestricted sodium content; 2) saralasin at 0.5 micrograms/kg/min or ACTH alone (0.5 U over 8 h) on the 7th day of a 10 meq sodium diet; and 3) ACTH and saralasin together on the 8th day while still on sodium restriction. AII was administered for the last 2 h of infusion 3. Plasma cortisol and aldosterone concentrations were measured at hourly intervals during the infusions and plasma renin activity was measured at 2 hourly intervals. ACTH infusion produced an increase in the plasma aldosterone concentration which was significantly greater during sodium restriction than when sodium intake was unlimited. This increase was not associated with an ACTH-induced rise in the plasma renin activity and was not significantly altered when ACTH was administered with saralasin. The rise in plasma cortisol concentration induced by ACTH was not significantly different when the normal subjects were on liberal and restricted sodium intakes. It is concluded that AII plays little if any acute role in increasing the stimulatory action of ACTH on aldosterone secretion during sodium restriction."}
{"id": "PMID:233671", "title": "Altered responsiveness to thyrotropin in thyroid slices of Graves' disease preoperatively treated with excess iodide.", "content": "In a previous paper, we demonstrated that the acute administration of excess iodide inhibits the adenylate cyclase-cAMP system in mouse thyroid lobes. In the present study, we examined whether presurgical therapy with stable iodide reduces the responsiveness to TSH in thyroid tissues from patients with Graves' disease. Eight patients with Graves' disease were presurgically treated with methimazole and stable iodide and six were given methimazole alone. Normal tissues from five patients with thyroid nodules were also tested. We have found that stimulation by TSH (5 and 50 mU/ml) of cAMP formation in thyroid slices from patients preoperatively treated with methimazole and iodide is significantly less than in slices from patients treated with methimazole alone. Similar observations were also made with other thyroid stimulators, such as prostaglandin E2 and 4-methylhistamine. Furthermore, thyroid slices from patients treated with methimazole alone responded to TSH to the same degree as slices of normal tissues. The data suggest that one of the reasons for the hyporesponsiveness to TSH in thyroids from patients with Graves' disease is preoperative treatment with stable iodide.", "contents": "Altered responsiveness to thyrotropin in thyroid slices of Graves' disease preoperatively treated with excess iodide. In a previous paper, we demonstrated that the acute administration of excess iodide inhibits the adenylate cyclase-cAMP system in mouse thyroid lobes. In the present study, we examined whether presurgical therapy with stable iodide reduces the responsiveness to TSH in thyroid tissues from patients with Graves' disease. Eight patients with Graves' disease were presurgically treated with methimazole and stable iodide and six were given methimazole alone. Normal tissues from five patients with thyroid nodules were also tested. We have found that stimulation by TSH (5 and 50 mU/ml) of cAMP formation in thyroid slices from patients preoperatively treated with methimazole and iodide is significantly less than in slices from patients treated with methimazole alone. Similar observations were also made with other thyroid stimulators, such as prostaglandin E2 and 4-methylhistamine. Furthermore, thyroid slices from patients treated with methimazole alone responded to TSH to the same degree as slices of normal tissues. The data suggest that one of the reasons for the hyporesponsiveness to TSH in thyroids from patients with Graves' disease is preoperative treatment with stable iodide."}
{"id": "PMID:233672", "title": "Pituitary-adrenal axis activity in treated congenital adrenal hyperplasia: static and dynamic studies.", "content": "The pituitary-adrenal axis activity was evaluated in 43 patients, treated for congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, by measuring plasma ACTH, 17-hydroxyprogesterone (17-OHP), testosterone, and aldosterone. Dynamic studies were performed by injecting 250 micrograms synthetic ACTH im and collecting blood samples 1 h later for steroid analysis. Twelve to fourteen hours after the last hydrocortisone dose given the evening before, plasma ACTH fluctuated widely from less than 10-475 pg/ml, 17-OHP exceeded normal values and varied from 1-275 ng/ml, while testosterone ranged from 3-151 ng/100 ml. The correlations between ACTH and 17-OHP (n equal 61, r equal 0.665, P less than 0.001) and between 17-OHP and testosterone (n = 43, r = 0.761, P less than 0.001) were good, while that between 17-OHP and aldosterone (n = 64, r = 0.512, P less than 0.001) was rather poor. One hour after ACTH injection, the mean level of 17-OHP was significantly increased as compared to the mean basal level [96.8 ng/ml +/- 10.6 (SE) as compared to 67.0 ng/ml +/- 8.1 (SE)]. However, only 12 out of the 48 tests showed a positive response equal to or greater than 100%, and the majority of these responses (10 out of 12) occurred when basal levels of 17-OHP were between 10-70 ng/ml. This suggests that when basal levels fall outside these values, the pituitary-adrenal axis is either too inhibited or too stimulated to react to exogenous ACTH. Of the 48 tests where 17-OHP was measured, 23 had basal level values within these limits, the mean being 40.3 ng/ml. The corresponding mean ACTH level was 99 pg/ml with a wide range (1-230 pg/ml). On the other hand, in prepubertal children who exhibited 17-OHP concentrations between 10-70 ng/ml, testosterone varied from 3-30 ng/100 ml, with a mean of 16.0 ng/100 ml +/- 1.9 (SE) which is not different from the mean level found in normal children [14.0 ng/100 ml +/- 1.3 (SE)]. Thus, under the influence of endogenous ACTH which is moderately increased, 17-OHP concentrations far exceed normal values, whereas plasma testosterone seems to be unaffected.", "contents": "Pituitary-adrenal axis activity in treated congenital adrenal hyperplasia: static and dynamic studies. The pituitary-adrenal axis activity was evaluated in 43 patients, treated for congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, by measuring plasma ACTH, 17-hydroxyprogesterone (17-OHP), testosterone, and aldosterone. Dynamic studies were performed by injecting 250 micrograms synthetic ACTH im and collecting blood samples 1 h later for steroid analysis. Twelve to fourteen hours after the last hydrocortisone dose given the evening before, plasma ACTH fluctuated widely from less than 10-475 pg/ml, 17-OHP exceeded normal values and varied from 1-275 ng/ml, while testosterone ranged from 3-151 ng/100 ml. The correlations between ACTH and 17-OHP (n equal 61, r equal 0.665, P less than 0.001) and between 17-OHP and testosterone (n = 43, r = 0.761, P less than 0.001) were good, while that between 17-OHP and aldosterone (n = 64, r = 0.512, P less than 0.001) was rather poor. One hour after ACTH injection, the mean level of 17-OHP was significantly increased as compared to the mean basal level [96.8 ng/ml +/- 10.6 (SE) as compared to 67.0 ng/ml +/- 8.1 (SE)]. However, only 12 out of the 48 tests showed a positive response equal to or greater than 100%, and the majority of these responses (10 out of 12) occurred when basal levels of 17-OHP were between 10-70 ng/ml. This suggests that when basal levels fall outside these values, the pituitary-adrenal axis is either too inhibited or too stimulated to react to exogenous ACTH. Of the 48 tests where 17-OHP was measured, 23 had basal level values within these limits, the mean being 40.3 ng/ml. The corresponding mean ACTH level was 99 pg/ml with a wide range (1-230 pg/ml). On the other hand, in prepubertal children who exhibited 17-OHP concentrations between 10-70 ng/ml, testosterone varied from 3-30 ng/100 ml, with a mean of 16.0 ng/100 ml +/- 1.9 (SE) which is not different from the mean level found in normal children [14.0 ng/100 ml +/- 1.3 (SE)]. Thus, under the influence of endogenous ACTH which is moderately increased, 17-OHP concentrations far exceed normal values, whereas plasma testosterone seems to be unaffected."}
{"id": "PMID:233673", "title": "Studies of the human testis. X. Properties of human chorionic gonadotropin receptor in adult testis and relation to intratesticular testosterone concentration.", "content": "Receptors for [125I]hCG were found in adult human testis. The specific binding of [125I]hCG to testicular receptor is temperature dependent and is a saturable process with respect to added receptor protein and hormone. Scatchard analysis revealed a dissociation constant of 5.0 X 10(-10) M, and 6.2 fmol binding site/mg protein. Intact unlabeled hCG effectively inhibits the specific binding of [125I]hCG to human testicular receptors. For inhibition of binding of [125I]hCG, the alpha subunit has 3.0% of the potency of intact hCG and the beta subunit has 0.4% of the potency of intact hCG. Specific binding is pH dependent, with an optimum at pH 7.4. Brief exposure to extremes of pH causes irreversible damage to the receptors. Incubation with protease and trypsin results in an almost complete loss of binding activity, while ribonuclease, deoxyribonuclease, phospholipase C, or neuraminidase treatment does not significantly alter hormone-binding activity. Binding activity was found to be positively correlated to the concentration of intratesticular testosterone.", "contents": "Studies of the human testis. X. Properties of human chorionic gonadotropin receptor in adult testis and relation to intratesticular testosterone concentration. Receptors for [125I]hCG were found in adult human testis. The specific binding of [125I]hCG to testicular receptor is temperature dependent and is a saturable process with respect to added receptor protein and hormone. Scatchard analysis revealed a dissociation constant of 5.0 X 10(-10) M, and 6.2 fmol binding site/mg protein. Intact unlabeled hCG effectively inhibits the specific binding of [125I]hCG to human testicular receptors. For inhibition of binding of [125I]hCG, the alpha subunit has 3.0% of the potency of intact hCG and the beta subunit has 0.4% of the potency of intact hCG. Specific binding is pH dependent, with an optimum at pH 7.4. Brief exposure to extremes of pH causes irreversible damage to the receptors. Incubation with protease and trypsin results in an almost complete loss of binding activity, while ribonuclease, deoxyribonuclease, phospholipase C, or neuraminidase treatment does not significantly alter hormone-binding activity. Binding activity was found to be positively correlated to the concentration of intratesticular testosterone."}
{"id": "PMID:233674", "title": "Urinary cAMP excretion during surgery: an index of successful parathyroidectomy in patients with primary hyperparathyroidism.", "content": "Urinary phosphate (Up) and urinary cAMP (UcAMP) excretion were determine in patients undergoing neck exploration for primary hyperparathyroidism in order to evaluate these parameters as indices of successful surgery. UcAMP fell below 1.5 micro mol/g creatinine in all 12 patients in whom single gland removal corrected hypercalcemia and in 0 of 3 patients in whom no parathyroid tissue was found. The mean time to drop below 1.5 was 2.0 +/- 0.8 h (mean /+- SD) from the time of parathyroidectomy. UcAMP fell below 1.5 in only 1 of 6 patients who had multiple enlarged parathyroid glands removed, irrespective of the outcome of surgery. Changes in Up excretion lagged behind UcAMP changes, so that within the time period studied Up fell to varying degrees in only 10 of 15 patients in whom hypercalcemia was corrected. A spurt in UcAMP excretion, possibly reflecting parathyroid hormone release due to manipulation of a parathyroid gland, occurred in 3 patients. The results suggest that an intraoperative fall in UcAMP below 1.5 predicts successful parathyroidectomy and that an intraoperative spurt in UcAMP may provide a clue to the location of abnormal parathyroid tissue.", "contents": "Urinary cAMP excretion during surgery: an index of successful parathyroidectomy in patients with primary hyperparathyroidism. Urinary phosphate (Up) and urinary cAMP (UcAMP) excretion were determine in patients undergoing neck exploration for primary hyperparathyroidism in order to evaluate these parameters as indices of successful surgery. UcAMP fell below 1.5 micro mol/g creatinine in all 12 patients in whom single gland removal corrected hypercalcemia and in 0 of 3 patients in whom no parathyroid tissue was found. The mean time to drop below 1.5 was 2.0 +/- 0.8 h (mean /+- SD) from the time of parathyroidectomy. UcAMP fell below 1.5 in only 1 of 6 patients who had multiple enlarged parathyroid glands removed, irrespective of the outcome of surgery. Changes in Up excretion lagged behind UcAMP changes, so that within the time period studied Up fell to varying degrees in only 10 of 15 patients in whom hypercalcemia was corrected. A spurt in UcAMP excretion, possibly reflecting parathyroid hormone release due to manipulation of a parathyroid gland, occurred in 3 patients. The results suggest that an intraoperative fall in UcAMP below 1.5 predicts successful parathyroidectomy and that an intraoperative spurt in UcAMP may provide a clue to the location of abnormal parathyroid tissue."}
{"id": "PMID:233675", "title": "Overnight plasma profiles of melatonin and certain adenohypophyseal hormones in men.", "content": "Melatonin levels exhibited a day-night rhythm with highest levels at night. Nocturnal plasma melatonin concentrations were unrelated to sleep stages, whereas secretion of GH was temporally related to slow wave sleep. Levels of corticotropin rose in the later sleep cycles. We found no relationship between endogenous nocturnal melatonin and adenohypophyseal hormone levels. The results indicate that in young men nocturnal levels of melatonin are controlled separately from those of LH, PRL, corticotropin, and GH.", "contents": "Overnight plasma profiles of melatonin and certain adenohypophyseal hormones in men. Melatonin levels exhibited a day-night rhythm with highest levels at night. Nocturnal plasma melatonin concentrations were unrelated to sleep stages, whereas secretion of GH was temporally related to slow wave sleep. Levels of corticotropin rose in the later sleep cycles. We found no relationship between endogenous nocturnal melatonin and adenohypophyseal hormone levels. The results indicate that in young men nocturnal levels of melatonin are controlled separately from those of LH, PRL, corticotropin, and GH."}
{"id": "PMID:233676", "title": "Cyproteroneacetate and ACTH adrenal function.", "content": "Cyproteroneacetate, an antiandrogenic and gonadotropin-inhibiting steroid, has a marked ACTH suppressive effect. In rats, adrenal atrophy and severe impairment of ACTH and corticosterone responses to stress are induced by a 10-day treatment with 3-0.75 mg/100 g BW cyproteroneacetate/day. Two weeks after cessation of treatment, the ACTH adrenal system has not yet recovered. The ACTH suppression is evident 6 h after a single dose. In 25 human volunteers, a single dose of 200 mg cyproteroneacetate impaired their ACTH and 11-deoxycorticosteroid response to 1 g metyrapone. A similar impairment was seen in 12 women on sequential treatment with cyproteroneacetate and ethinyl estradiol. In 4 out of 11 children treated for precocious puberty, random plasma ACTH and cortisol measurements, cortisol responses to ACTH, and ACTH and cortisol responses to insulin-induced hypoglycemia revealed severely impaired ACTH adrenal function. Questionable impairment was found in 2 out of 11 and normal function in 5 out of 11 children. In 10 patients with endogenous elevated plasma ACTH, 10 days of treatment with cyproteroneacetate, in addition to the steroid substitution, diminished the morning plasma ACTH levels. It is concluded that cyproteroneactate has a pronounced ACTH-suppressive effect. The individual susceptibility of treated patients varies and the effect is dose dependent. A cortisol-like effect must be assumed, because cyproteroneacetate-treated animals and patients under therapy can withstand stress situations without signs of adrenal insufficiency. ACTH adrenal function must, however, be closely watched in treated patients and steroid cover must be considered in conditions of stress. Great care has to be taken when the drug, with its own \"stress-protective\" effect, is withdrawn. The recovery of ACTH adrenal function may take several months.", "contents": "Cyproteroneacetate and ACTH adrenal function. Cyproteroneacetate, an antiandrogenic and gonadotropin-inhibiting steroid, has a marked ACTH suppressive effect. In rats, adrenal atrophy and severe impairment of ACTH and corticosterone responses to stress are induced by a 10-day treatment with 3-0.75 mg/100 g BW cyproteroneacetate/day. Two weeks after cessation of treatment, the ACTH adrenal system has not yet recovered. The ACTH suppression is evident 6 h after a single dose. In 25 human volunteers, a single dose of 200 mg cyproteroneacetate impaired their ACTH and 11-deoxycorticosteroid response to 1 g metyrapone. A similar impairment was seen in 12 women on sequential treatment with cyproteroneacetate and ethinyl estradiol. In 4 out of 11 children treated for precocious puberty, random plasma ACTH and cortisol measurements, cortisol responses to ACTH, and ACTH and cortisol responses to insulin-induced hypoglycemia revealed severely impaired ACTH adrenal function. Questionable impairment was found in 2 out of 11 and normal function in 5 out of 11 children. In 10 patients with endogenous elevated plasma ACTH, 10 days of treatment with cyproteroneacetate, in addition to the steroid substitution, diminished the morning plasma ACTH levels. It is concluded that cyproteroneactate has a pronounced ACTH-suppressive effect. The individual susceptibility of treated patients varies and the effect is dose dependent. A cortisol-like effect must be assumed, because cyproteroneacetate-treated animals and patients under therapy can withstand stress situations without signs of adrenal insufficiency. ACTH adrenal function must, however, be closely watched in treated patients and steroid cover must be considered in conditions of stress. Great care has to be taken when the drug, with its own \"stress-protective\" effect, is withdrawn. The recovery of ACTH adrenal function may take several months."}
{"id": "PMID:233677", "title": "Changes of plasma lipid metabolism in males during estrogen treatment for prostatic carcinoma.", "content": "Fourteen patients with prostatic carcinoma were treated with 1.0-0.5 mg ethinyl estradiol orally daily and 160-80 mg polyestradiol phosphate im monthly. Lipid concentrations were determined in plasma and the high density lipoprotein fraction, and the plasma lecithin-cholesterol acyl transfer rate was measured before and 1 and 6 months after the start of therapy. During treatment, the concentration of total cholesterol was unchanged while there was a 60% increase of high density lipoprotein-total cholesterol. Triglyceride (TG) concentration increased 40%, indicating an augmented level of very low density lipoprotein concentration. The plasma lecithin-cholesterol acyl transfer rate increase 20-35%, indicating that an increased rate of production and turnover of TG, cholesteryl esters, and very low density lipoproteins probably was a main cause of the elevated TG concentration. The potential effects on the development of atherosclerosis by the plasma lipid changes during estrogen treatment are discussed.", "contents": "Changes of plasma lipid metabolism in males during estrogen treatment for prostatic carcinoma. Fourteen patients with prostatic carcinoma were treated with 1.0-0.5 mg ethinyl estradiol orally daily and 160-80 mg polyestradiol phosphate im monthly. Lipid concentrations were determined in plasma and the high density lipoprotein fraction, and the plasma lecithin-cholesterol acyl transfer rate was measured before and 1 and 6 months after the start of therapy. During treatment, the concentration of total cholesterol was unchanged while there was a 60% increase of high density lipoprotein-total cholesterol. Triglyceride (TG) concentration increased 40%, indicating an augmented level of very low density lipoprotein concentration. The plasma lecithin-cholesterol acyl transfer rate increase 20-35%, indicating that an increased rate of production and turnover of TG, cholesteryl esters, and very low density lipoproteins probably was a main cause of the elevated TG concentration. The potential effects on the development of atherosclerosis by the plasma lipid changes during estrogen treatment are discussed."}
{"id": "PMID:233678", "title": "Renal-resistant hormonoplethoric hypoparathyroidism with evidence for a defective response to cAMP.", "content": "A 15.5-yr-old black male is reported with hypocalcemia, hyperphosphatemia, and severe osteitis fibrosa cystica. While hypocalcemic and hyperphosphatemic, the circulating parathyroid hormone (PTH) level and urinary cAMP excretion were increased. An infusion of exogenous PTH produced a normal maximal excretion of urinary cAMP but failed to increase phosphate excretion. Correction of the hypocalcemia by administration of 200,000 U vitamin D daily lowered the endogenous PTH level and basal excretion of cAMP to normal; at that time, infusion of PTH produced both a normal rise in urinary cAMP and a normal phosphaturic response. This pattern of response suggests pseudohypoparathyroidism with a calcium-sensitive defect in renal phosphate transport distal to the PTH receptor adenyl cyclase mechanism, producing hyperphosphatemia, hypocalcemia, and secondary hyperparathyroidism. The osteitis fibrosa cystica was presumably due to the increased PTH, suggesting that resistance to PTH was present in kidney but not bone.", "contents": "Renal-resistant hormonoplethoric hypoparathyroidism with evidence for a defective response to cAMP. A 15.5-yr-old black male is reported with hypocalcemia, hyperphosphatemia, and severe osteitis fibrosa cystica. While hypocalcemic and hyperphosphatemic, the circulating parathyroid hormone (PTH) level and urinary cAMP excretion were increased. An infusion of exogenous PTH produced a normal maximal excretion of urinary cAMP but failed to increase phosphate excretion. Correction of the hypocalcemia by administration of 200,000 U vitamin D daily lowered the endogenous PTH level and basal excretion of cAMP to normal; at that time, infusion of PTH produced both a normal rise in urinary cAMP and a normal phosphaturic response. This pattern of response suggests pseudohypoparathyroidism with a calcium-sensitive defect in renal phosphate transport distal to the PTH receptor adenyl cyclase mechanism, producing hyperphosphatemia, hypocalcemia, and secondary hyperparathyroidism. The osteitis fibrosa cystica was presumably due to the increased PTH, suggesting that resistance to PTH was present in kidney but not bone."}
{"id": "PMID:233679", "title": "\"Normal suppression\" to dexamethasone in Cushing's disease: an expression of decreased metabolic clearance for dexamethasone.", "content": "The adrenal cortical function of a patient with pituitary-dependent Cushing's syndrome exhibited normal responsiveness to conventional doses of dexamethasone (Dex) over several years of evaluation. \"Periodic hormonogenesis\" did not seem to explain the phenomenon. Plasma concentrations of Dex were measured to ascertain whether an abnormality in Dex metabolism might explain the apparent discrepancy in Dex responsiveness. Plasma levels of Dex after oral administration of the steroid were higher than normal, suggesting that decreased clearance of Dex accounts for the phenomenon of \"normal suppression\" in this patient with Cushing's syndrome.", "contents": "\"Normal suppression\" to dexamethasone in Cushing's disease: an expression of decreased metabolic clearance for dexamethasone. The adrenal cortical function of a patient with pituitary-dependent Cushing's syndrome exhibited normal responsiveness to conventional doses of dexamethasone (Dex) over several years of evaluation. \"Periodic hormonogenesis\" did not seem to explain the phenomenon. Plasma concentrations of Dex were measured to ascertain whether an abnormality in Dex metabolism might explain the apparent discrepancy in Dex responsiveness. Plasma levels of Dex after oral administration of the steroid were higher than normal, suggesting that decreased clearance of Dex accounts for the phenomenon of \"normal suppression\" in this patient with Cushing's syndrome."}
{"id": "PMID:233680", "title": "Effect of indomethacin on the hypothalamic-pituitary-adrenal axis in man.", "content": "The effect of the cyclo-oxygenase inhibitor, indomethacin, on hypothalamic-pituitary-adrenal function was investigated in five normal males. Baseline 0800 and 1600 h plasma ACTH and cortisol, plasma ACTH and 11-deoxycortisol responses to metyrapone, and plasma cortisol responses to dexamethasone and exogenous ACTH were not affected by indomethacin. However, the area under the curve for plasma ACTH after iv injection of regular insulin (0.1 U/kg) was significantly decreased during indomethacin administration (control, 88.0 +/- 32.6 cm2, mean +/- sd; indomethacin, 47.6 +/- 23.1, P less than 0.01). Plasma cortisol levels were decreased only at 30 min. Our results support the hypothesis that prostaglandins or any of their precursors play a role in the hypothalamic control of ACTH secretion and indicate that evaluation of hypophyseal ACTH secretory capacity by means of insulin-induced hypoglycemia may yield abnormal results in patients receiving indomethacin.", "contents": "Effect of indomethacin on the hypothalamic-pituitary-adrenal axis in man. The effect of the cyclo-oxygenase inhibitor, indomethacin, on hypothalamic-pituitary-adrenal function was investigated in five normal males. Baseline 0800 and 1600 h plasma ACTH and cortisol, plasma ACTH and 11-deoxycortisol responses to metyrapone, and plasma cortisol responses to dexamethasone and exogenous ACTH were not affected by indomethacin. However, the area under the curve for plasma ACTH after iv injection of regular insulin (0.1 U/kg) was significantly decreased during indomethacin administration (control, 88.0 +/- 32.6 cm2, mean +/- sd; indomethacin, 47.6 +/- 23.1, P less than 0.01). Plasma cortisol levels were decreased only at 30 min. Our results support the hypothesis that prostaglandins or any of their precursors play a role in the hypothalamic control of ACTH secretion and indicate that evaluation of hypophyseal ACTH secretory capacity by means of insulin-induced hypoglycemia may yield abnormal results in patients receiving indomethacin."}
{"id": "PMID:233681", "title": "Formation of 2- and 4-hydroxyestrogens by brain, pituitary, and liver of the human fetus.", "content": "When [6,7-3H]estradiol was incubated with tissue homogenates of the brain, the pituitary, and the liver of two human female fetuses, a number of radioactive metabolites more \"polar\" than the incubated substrate were detected. Among these, the identification of two types of catecholestrogens, i.e. the 2- and 4-hydroxyestrogens, was of major interest. Compared on the basis of wet weight of tissues (250 mg), the conversion of estradiol to 2-hydroxyestrogens (2-hydroxyestradiol and 2-hydroxyestrone) was 0.8% in the frontal cortex, 1.0% in the hypothalamus, 2.1% in the pituitary, and 7.8% in the liver. For the first time, the formation of 4-hydroxyestrogens was demonstrated. The percentages of incubated estradiol hydroxylated at C-atom 4 (4-hydroxyestradiol and 4-hydroxyestrone) were 0.5 in the cortex, 0.4% in the hypothalamus, .1% in the pituitary, and 0.5% in the liver. The results show that fetal brain and pituitary tissue can hydroxylate estradiol in positions 2 and 4 to a similar extent, whereas in the liver, about 15 times more 2-hydroxy than 4-hydroxy compounds are formed. Moreover, the 2-hydroxylating capacity of the liver is definitely greater than that of the brain, whereas the 4-hydroxylating capacity is about the same as that of the brain.", "contents": "Formation of 2- and 4-hydroxyestrogens by brain, pituitary, and liver of the human fetus. When [6,7-3H]estradiol was incubated with tissue homogenates of the brain, the pituitary, and the liver of two human female fetuses, a number of radioactive metabolites more \"polar\" than the incubated substrate were detected. Among these, the identification of two types of catecholestrogens, i.e. the 2- and 4-hydroxyestrogens, was of major interest. Compared on the basis of wet weight of tissues (250 mg), the conversion of estradiol to 2-hydroxyestrogens (2-hydroxyestradiol and 2-hydroxyestrone) was 0.8% in the frontal cortex, 1.0% in the hypothalamus, 2.1% in the pituitary, and 7.8% in the liver. For the first time, the formation of 4-hydroxyestrogens was demonstrated. The percentages of incubated estradiol hydroxylated at C-atom 4 (4-hydroxyestradiol and 4-hydroxyestrone) were 0.5 in the cortex, 0.4% in the hypothalamus, .1% in the pituitary, and 0.5% in the liver. The results show that fetal brain and pituitary tissue can hydroxylate estradiol in positions 2 and 4 to a similar extent, whereas in the liver, about 15 times more 2-hydroxy than 4-hydroxy compounds are formed. Moreover, the 2-hydroxylating capacity of the liver is definitely greater than that of the brain, whereas the 4-hydroxylating capacity is about the same as that of the brain."}
{"id": "PMID:233682", "title": "Pathophysiological studies in idiopathic hypercalciuria: use of an oral calcium tolerance test to characterize distinctive hypercalciuric subgroups.", "content": "Twenty-one unselected patients with recurrent nephrolithiasis and normocalcemic hypercalciuria with or without hypophosphatemia and 18 normal subjects were studied with an oral calcium tolerance test and for 3- to 5-day periods while consuming a low normal (400 mg) and high-normal (1000 mg) calcium intake. The oral calcium tolerance test consisted of the measurement of the calcemic, calciuric, and parathyroid (assessed by determinations of serum immunoreactive parathyroid hormone and nephrogenous cAMP) responses to acute 1000- or 350-mg doses of calcium. Nineteen patients displayed normal results for basal serum calcium, parathyroid function, and fasting calcium excretion, and striking calcemic (mean increase in serum calcium, 0.9 vs. 0.2 mg/dl in the normal subjects) and calciuric (mean increase in urinary calcium, 0.33 vs. 0.15 mg calcium/100 ml GF in the normal subjects) responses to the 1000-mg calcium tolerance test, associated with a mean 54% suppression in nephrogenous cAMP. These patients were operationally defined as having \"absorptive\" hypercalciuria. The variable occurrence of hypophosphatemia in this group suggested that the pathogenesis of \"absorptive\" hypercalciuria may be complex and/or multifactorial. There were strong positive correlations between the calciuric response to the calcium tolerance test and fractional isotopic calcium absorption (r = 0.75, P less than 0.00), the calcemic responses to the test (r = 0.71, P less than 0.001) and the calciuric responses noted on the 1000- vs. the 400-mg daily calcium intake (r = 0.78, P less than 0.001). Two patients displayed low or low normal basal serum calcium, increased parathyroid function, increased fasting calcium excretion, and a striking calciuric but minimal calcemic response to the 1000-mg calcium tolerance test, associated with a moderate suppression in nephrogenous cAMP. These patients were operationally defined as having \"renal\" hypercalciuria. Several lines of evidence indicated that the hyperparathyroidism in these patients was physiological or secondary, including the near normalization of parathyroid function on the daily 1000-mg calcium intake. A steep slope of calcium excretion on calcium intake (due to increased calcium absorption) was noted in all hypercalciuric patients and accounted for the significantly improved diagnostic accuracy of screening patients for hypercalciuria on the high-normal calcium intake. The simple measurement of total cAMP excretion (nanomoles per 100 ml GF) and urinary calcium on the 1000-mg daily calcium intake seemed to provide reliable separation of patients with \"renal\" from those with \"absorptive\" hypercalciuria. A physiological (350 mg) dose of oral calcium produced a 30% suppression of nephrogenous cAMP in normal subjects; this suggests that dietary calcium exerts an important control of parathyroid function under physiological circumstances.", "contents": "Pathophysiological studies in idiopathic hypercalciuria: use of an oral calcium tolerance test to characterize distinctive hypercalciuric subgroups. Twenty-one unselected patients with recurrent nephrolithiasis and normocalcemic hypercalciuria with or without hypophosphatemia and 18 normal subjects were studied with an oral calcium tolerance test and for 3- to 5-day periods while consuming a low normal (400 mg) and high-normal (1000 mg) calcium intake. The oral calcium tolerance test consisted of the measurement of the calcemic, calciuric, and parathyroid (assessed by determinations of serum immunoreactive parathyroid hormone and nephrogenous cAMP) responses to acute 1000- or 350-mg doses of calcium. Nineteen patients displayed normal results for basal serum calcium, parathyroid function, and fasting calcium excretion, and striking calcemic (mean increase in serum calcium, 0.9 vs. 0.2 mg/dl in the normal subjects) and calciuric (mean increase in urinary calcium, 0.33 vs. 0.15 mg calcium/100 ml GF in the normal subjects) responses to the 1000-mg calcium tolerance test, associated with a mean 54% suppression in nephrogenous cAMP. These patients were operationally defined as having \"absorptive\" hypercalciuria. The variable occurrence of hypophosphatemia in this group suggested that the pathogenesis of \"absorptive\" hypercalciuria may be complex and/or multifactorial. There were strong positive correlations between the calciuric response to the calcium tolerance test and fractional isotopic calcium absorption (r = 0.75, P less than 0.00), the calcemic responses to the test (r = 0.71, P less than 0.001) and the calciuric responses noted on the 1000- vs. the 400-mg daily calcium intake (r = 0.78, P less than 0.001). Two patients displayed low or low normal basal serum calcium, increased parathyroid function, increased fasting calcium excretion, and a striking calciuric but minimal calcemic response to the 1000-mg calcium tolerance test, associated with a moderate suppression in nephrogenous cAMP. These patients were operationally defined as having \"renal\" hypercalciuria. Several lines of evidence indicated that the hyperparathyroidism in these patients was physiological or secondary, including the near normalization of parathyroid function on the daily 1000-mg calcium intake. A steep slope of calcium excretion on calcium intake (due to increased calcium absorption) was noted in all hypercalciuric patients and accounted for the significantly improved diagnostic accuracy of screening patients for hypercalciuria on the high-normal calcium intake. The simple measurement of total cAMP excretion (nanomoles per 100 ml GF) and urinary calcium on the 1000-mg daily calcium intake seemed to provide reliable separation of patients with \"renal\" from those with \"absorptive\" hypercalciuria. A physiological (350 mg) dose of oral calcium produced a 30% suppression of nephrogenous cAMP in normal subjects; this suggests that dietary calcium exerts an important control of parathyroid function under physiological circumstances."}
{"id": "PMID:233683", "title": "Cortisol and androgen secretion in a case of Nelson's syndrome with paratesticular tumors: response to cyproheptadine therapy.", "content": "Bilateral paratesticular tumors were observed in a 32-yr-old man 14 yr after he developed a pituitary tumor after adrenalectomy for Cushing's disease (Nelson's syndrome). Plasma ACTH concentrations were markedly elevated (mean, 6350 pg/ml), but urinary free cortisol concentrations were low (27-31 micrograms/24 h). Catheterization revealed a spermatic to peripheral venous gradient for cortisol consistent with secretion of this steroid by the tumor. This was confirmed by decreased cortisol excretion after tumor excision. Serum androgen (testosterone, androstenedione, dihydrotestosterone, and dehydroepiandrosterone-sulfate) and progestin (progesterone and 17-hydroxyprogesterone) concentrations were decreased and did not decline further after tumor removal. These latter observations suggested that the paratesticular tumors did not secrete appreciable testosterone or any of its immediate precursors. Serum gonadotropin levels were also low. Cyproheptadine treatment resulted in a marked lowering of plasma ACTH concentrations (221-320 pg/ml). This was associated with an increase in both plasma LH and testosterone concentrations. These observations are consistent with the hypothesis that ACTH may directly affect LH and testosterone secretion.", "contents": "Cortisol and androgen secretion in a case of Nelson's syndrome with paratesticular tumors: response to cyproheptadine therapy. Bilateral paratesticular tumors were observed in a 32-yr-old man 14 yr after he developed a pituitary tumor after adrenalectomy for Cushing's disease (Nelson's syndrome). Plasma ACTH concentrations were markedly elevated (mean, 6350 pg/ml), but urinary free cortisol concentrations were low (27-31 micrograms/24 h). Catheterization revealed a spermatic to peripheral venous gradient for cortisol consistent with secretion of this steroid by the tumor. This was confirmed by decreased cortisol excretion after tumor excision. Serum androgen (testosterone, androstenedione, dihydrotestosterone, and dehydroepiandrosterone-sulfate) and progestin (progesterone and 17-hydroxyprogesterone) concentrations were decreased and did not decline further after tumor removal. These latter observations suggested that the paratesticular tumors did not secrete appreciable testosterone or any of its immediate precursors. Serum gonadotropin levels were also low. Cyproheptadine treatment resulted in a marked lowering of plasma ACTH concentrations (221-320 pg/ml). This was associated with an increase in both plasma LH and testosterone concentrations. These observations are consistent with the hypothesis that ACTH may directly affect LH and testosterone secretion."}
{"id": "PMID:233684", "title": "Urinary free 18-hydroxy-11-desoxycorticosterone excretion in normal and hypertensive patients.", "content": "One hundred fourteen hypertensives and 20 normal controls were examined using a new clinical technique of measuring 24-h urinary free 18-hydroxy-11-desoxycorticosterone (18-OH-DOC) excretion in response to dietary salt manipulations and ACTH injections. The object was to avoid potential errors of random plasma sampling. Mean urinary free 18-OH-DOC in normals on 110 milliequivalent sodium diet was 1.84 +/- 0.69 microgram (mean +/- SD) and represented about 2% of the daily secretion rate of this steroid. Both in normals and hypertensives, urinary free 18-OH-DOC approximately doubled on low salt (P less than 0.01 for each) and rose about 10 times in response to ACTH injection (P less than 0.05 and P less than 0.01, respectively). Plasma and urinary free 18-OH-DOC showed good correlation in patients with essential hypertension on a low salt diet (r = 0.45, P less than 0.01). Suppressed renin patients showed no propensity toward excess 18-OH-DOC excretion and hypertensives with elevated 18-OH-DOC could not be distinguished by their aldosterone levels, cortisol levels, nor their responses to various stimuli. These data suggest 18-OH-DOC is predominantly secreted under ACTH control and, to a smaller extent, in response to salt changes. Hypertension characterized by chronic overproduction of 18-OH-DOC forms only a small percentage of the hypertensive population. It is proposed that measuring 24-h urinary free 18-OH-DOC excretion may be the best method of assessing its rate of secretion without resorting to injection of radiolabeled material.", "contents": "Urinary free 18-hydroxy-11-desoxycorticosterone excretion in normal and hypertensive patients. One hundred fourteen hypertensives and 20 normal controls were examined using a new clinical technique of measuring 24-h urinary free 18-hydroxy-11-desoxycorticosterone (18-OH-DOC) excretion in response to dietary salt manipulations and ACTH injections. The object was to avoid potential errors of random plasma sampling. Mean urinary free 18-OH-DOC in normals on 110 milliequivalent sodium diet was 1.84 +/- 0.69 microgram (mean +/- SD) and represented about 2% of the daily secretion rate of this steroid. Both in normals and hypertensives, urinary free 18-OH-DOC approximately doubled on low salt (P less than 0.01 for each) and rose about 10 times in response to ACTH injection (P less than 0.05 and P less than 0.01, respectively). Plasma and urinary free 18-OH-DOC showed good correlation in patients with essential hypertension on a low salt diet (r = 0.45, P less than 0.01). Suppressed renin patients showed no propensity toward excess 18-OH-DOC excretion and hypertensives with elevated 18-OH-DOC could not be distinguished by their aldosterone levels, cortisol levels, nor their responses to various stimuli. These data suggest 18-OH-DOC is predominantly secreted under ACTH control and, to a smaller extent, in response to salt changes. Hypertension characterized by chronic overproduction of 18-OH-DOC forms only a small percentage of the hypertensive population. It is proposed that measuring 24-h urinary free 18-OH-DOC excretion may be the best method of assessing its rate of secretion without resorting to injection of radiolabeled material."}
{"id": "PMID:233685", "title": "On the isolation of human pituitary hormones.", "content": "Six human pituitary hormones can be obtained from a single batch of human pituitary glands by the procedure described. Starting from an acetone powder of the glands, the hormones are segregated into three fractions; one containing GH and PRL, a second containing the glycoprotein hormones, and the third fraction containing smaller peptides including ACTH and MSH. Clinical grade GH is extracted from the residue at alkaline pH, followed by a series of ammonium sulfate and pH fractionations. Further chromatography on G-100 yields a highly purified GH preparation. FSH is purified by chromatography on carboxymethyl cellulose at pH 5.4 followed by gel filtration on G-100 and fractionation on sulfopropyl Sephadex C-50 at pH 5.4. LH and TSH are separated by DEAE-cellulose chromatography at pH 9.5. The GH and glycoprotein hormones are recovered in a highly purified form and good yields. The GH is obtained in an active form which is easily soluble and well suited for clinical use. A large part of the PRL is also saved during the extraction procedure.", "contents": "On the isolation of human pituitary hormones. Six human pituitary hormones can be obtained from a single batch of human pituitary glands by the procedure described. Starting from an acetone powder of the glands, the hormones are segregated into three fractions; one containing GH and PRL, a second containing the glycoprotein hormones, and the third fraction containing smaller peptides including ACTH and MSH. Clinical grade GH is extracted from the residue at alkaline pH, followed by a series of ammonium sulfate and pH fractionations. Further chromatography on G-100 yields a highly purified GH preparation. FSH is purified by chromatography on carboxymethyl cellulose at pH 5.4 followed by gel filtration on G-100 and fractionation on sulfopropyl Sephadex C-50 at pH 5.4. LH and TSH are separated by DEAE-cellulose chromatography at pH 9.5. The GH and glycoprotein hormones are recovered in a highly purified form and good yields. The GH is obtained in an active form which is easily soluble and well suited for clinical use. A large part of the PRL is also saved during the extraction procedure."}
{"id": "PMID:233686", "title": "Plasma parathyroid hormone and calcium are related to sleep stage cycles.", "content": "To study dynamic interactions among parathyroid hormone (PTH), plasma calcium, and brain states, seven normal subjects were studied for a total of eight nights in our sleep laboratories. Plasma samples were obtained at 10- to 20-min intervals for PTH and calcium determinations. Electroencephalogram, eye movements, and muscle tone were recorded to determine sleep stages. On each night, several distinct peaks in PTH concentration were seen, which in some cases exceeded the all night mean PTH by as much as 300%. Peaks in plasma PTH were significantly nonrandom and tended to recur about every 100 min. PTH concentration was significantly related to cycles of stages 3 and 4 sleep. Total plasma calcium varied less but was significantly related to cycles of rapid eye movement sleep and to cycles of stage 2 sleep. PTH and calcium were significantly interrelated, especially at high frequencies above 40 cycles/day (1 cycle 36 min). In the 14.4 cycles/day (1 cycle/100 min) frequency range where most PTH and calcium variability was found, however, PTH and calcium were more closely related to sleep stages than to each other. These results suggest that the regulation of PTH and calcium is complex and may involve interactions with neural systems.", "contents": "Plasma parathyroid hormone and calcium are related to sleep stage cycles. To study dynamic interactions among parathyroid hormone (PTH), plasma calcium, and brain states, seven normal subjects were studied for a total of eight nights in our sleep laboratories. Plasma samples were obtained at 10- to 20-min intervals for PTH and calcium determinations. Electroencephalogram, eye movements, and muscle tone were recorded to determine sleep stages. On each night, several distinct peaks in PTH concentration were seen, which in some cases exceeded the all night mean PTH by as much as 300%. Peaks in plasma PTH were significantly nonrandom and tended to recur about every 100 min. PTH concentration was significantly related to cycles of stages 3 and 4 sleep. Total plasma calcium varied less but was significantly related to cycles of rapid eye movement sleep and to cycles of stage 2 sleep. PTH and calcium were significantly interrelated, especially at high frequencies above 40 cycles/day (1 cycle 36 min). In the 14.4 cycles/day (1 cycle/100 min) frequency range where most PTH and calcium variability was found, however, PTH and calcium were more closely related to sleep stages than to each other. These results suggest that the regulation of PTH and calcium is complex and may involve interactions with neural systems."}
{"id": "PMID:233687", "title": "Treatment of Cushing's syndrome with trilostane (WIN 24,540), an inhibitor of adrenal steroid biosynthesis.", "content": "Seven patients with Cushing's syndrome were treated with trilostane (WIN 24,540) 4 alpha,5-epoxy-17 beta-hydroxy-3-oxo-5 alpha-androstane-2 alpha-carbonitrile), an inhibitor of adrenal steroid biosynthesis. Trilostane treatment reduced steroid biosynthesis and it also improved biochemical manifestations of the disease in all of the patients treated. The average cortisol secretory rate decreased significantly with treatment, from 47.1 to 23.4 mg/24 h (P less than 0.005), and urinary 17-hydroxycorticosteroids decreased from 15.7 to 8.7 mg/24 h (P less than 0.01). Urinary free cortisol excretion decreased from 277 to 88 microgram/24 h (P less than 0.01), and 0800 h plasma cortisol levels declined from 25.0 to 12.0 microgram/dl (P less than 0.05). Conversely, dehydroepiandrosterone sulfate excretion in urine increased from 1.3 to 5.8 mg/24 h (P less than 0.0025) and in plasma increased from 162 mg/24 h (P less than 0.025). Plasma and urinary free dehydroepiandrosterone increased 2-fold. Urinary 17-ketosteroid excretion increased from 18 to 43 mg/24 h (P less than 0.001). A significant reduction in urinary excretion of tetrahydroaldosterone, tetrahydrodeoxycorticosterone, and 18-hydroxytetrahydrodeoxycorticosterone was observed with treatment. Inhibition of steroid biosynthesis was accompanied by a 2-fold increase in PRA and no change in serum cholesterol levels. Mean arterial blood pressure decreased with treatment from 109 to 97 mm Hg (P less than 0.005), and fasting blood sugar decreased from 117 to 98 mg/dl (P less than 0.005), accompanied by rise in plasma potassium levels from 3.8 to 4.3 milliequivalents/liter (P less than 0.025). Two patients on long term therapy also showed an improvement in clinical features of their disease. There were no significant treatment-related carcinoma, simultaneously producing both an excessive amount of cortisol and ACTH, is described. It is concluded that trilostane is an effective inhibitor of 3 beta-hydroxysteroid dehydrogenase enzyme system in human adrenal gland; it inhibits biosynthesis of cortisol and it is useful in the treatment of Cushing's syndrome.", "contents": "Treatment of Cushing's syndrome with trilostane (WIN 24,540), an inhibitor of adrenal steroid biosynthesis. Seven patients with Cushing's syndrome were treated with trilostane (WIN 24,540) 4 alpha,5-epoxy-17 beta-hydroxy-3-oxo-5 alpha-androstane-2 alpha-carbonitrile), an inhibitor of adrenal steroid biosynthesis. Trilostane treatment reduced steroid biosynthesis and it also improved biochemical manifestations of the disease in all of the patients treated. The average cortisol secretory rate decreased significantly with treatment, from 47.1 to 23.4 mg/24 h (P less than 0.005), and urinary 17-hydroxycorticosteroids decreased from 15.7 to 8.7 mg/24 h (P less than 0.01). Urinary free cortisol excretion decreased from 277 to 88 microgram/24 h (P less than 0.01), and 0800 h plasma cortisol levels declined from 25.0 to 12.0 microgram/dl (P less than 0.05). Conversely, dehydroepiandrosterone sulfate excretion in urine increased from 1.3 to 5.8 mg/24 h (P less than 0.0025) and in plasma increased from 162 mg/24 h (P less than 0.025). Plasma and urinary free dehydroepiandrosterone increased 2-fold. Urinary 17-ketosteroid excretion increased from 18 to 43 mg/24 h (P less than 0.001). A significant reduction in urinary excretion of tetrahydroaldosterone, tetrahydrodeoxycorticosterone, and 18-hydroxytetrahydrodeoxycorticosterone was observed with treatment. Inhibition of steroid biosynthesis was accompanied by a 2-fold increase in PRA and no change in serum cholesterol levels. Mean arterial blood pressure decreased with treatment from 109 to 97 mm Hg (P less than 0.005), and fasting blood sugar decreased from 117 to 98 mg/dl (P less than 0.005), accompanied by rise in plasma potassium levels from 3.8 to 4.3 milliequivalents/liter (P less than 0.025). Two patients on long term therapy also showed an improvement in clinical features of their disease. There were no significant treatment-related carcinoma, simultaneously producing both an excessive amount of cortisol and ACTH, is described. It is concluded that trilostane is an effective inhibitor of 3 beta-hydroxysteroid dehydrogenase enzyme system in human adrenal gland; it inhibits biosynthesis of cortisol and it is useful in the treatment of Cushing's syndrome."}
{"id": "PMID:233688", "title": "Effects of thyroid-stimulating hormone on human thyroid carcinoma and adjacent normal tissue.", "content": "Effects of TSH on the adenylate cyclase-cAMP system and some parameters of intermediary metabolism were investigated in human thyroid carcinoma and adjacent normal thyroid tissue. Basal adenylate cyclase activity and cAMP concentrations were significantly higher in carcinomatous tissue. Basal [1-14C]glucose oxidation, 32Pi incorporation into phospholipids, and organification of iodide were similar in both tissues. Stimulation of cAMP by TSH was significantly greater in normal compared to carcinomatous tissue. In neither tissue was there a good correlation between TSH stimulation of adenylate cyclase activity and cAMP concentrations. The TSH stimulation of 32Pi incorporation into phospholipids by TSH was significantly greater in normal tissue. The mean effect of TSH on iodide organification and glucose oxidation was similar in normal and carcinomatous tissue. Although specific binding of TSH was demonstrated in both normal and carcinomatous tissue, it did not correlate very well with stimulation of adenylate cyclase activity. Hormones other than TSH also augmented adenylate cyclase activity in two of the carcinomas. In individual patients, the relative responsivity of carcinomatous tissue compared to normal was not always consistent when all of the metabolic parameters were considered.", "contents": "Effects of thyroid-stimulating hormone on human thyroid carcinoma and adjacent normal tissue. Effects of TSH on the adenylate cyclase-cAMP system and some parameters of intermediary metabolism were investigated in human thyroid carcinoma and adjacent normal thyroid tissue. Basal adenylate cyclase activity and cAMP concentrations were significantly higher in carcinomatous tissue. Basal [1-14C]glucose oxidation, 32Pi incorporation into phospholipids, and organification of iodide were similar in both tissues. Stimulation of cAMP by TSH was significantly greater in normal compared to carcinomatous tissue. In neither tissue was there a good correlation between TSH stimulation of adenylate cyclase activity and cAMP concentrations. The TSH stimulation of 32Pi incorporation into phospholipids by TSH was significantly greater in normal tissue. The mean effect of TSH on iodide organification and glucose oxidation was similar in normal and carcinomatous tissue. Although specific binding of TSH was demonstrated in both normal and carcinomatous tissue, it did not correlate very well with stimulation of adenylate cyclase activity. Hormones other than TSH also augmented adenylate cyclase activity in two of the carcinomas. In individual patients, the relative responsivity of carcinomatous tissue compared to normal was not always consistent when all of the metabolic parameters were considered."}
{"id": "PMID:233689", "title": "Alteration of feedback mechanism of estrogen on gonadotropin by sulpiride-induced hyperprolactinemia.", "content": "Four normally cycling women received an iv injection of 20 mg Premarin (conjugated estrogens equivalent to 20 mg estrone sulfate) on the seventh day of two consecutive cycles; the second experiment was performed under sulpiride-induced hyperprolactinemia (mean PRL level = 906 microU MRC standard 71/222 per ml; significantly 7.8 times greater than mean control level of 115 microU MRC standard 71/222 per ml, P less than 0.001). In comparison to the control experiment, sulpiride-induced hyperprolactinemia prevented the occurrence of any gonadotropin peak within the 84 h of estrogen administration; the negative feedback effect of estrogen on gonadotropin secretion was maintained and was even potentiated. These alterations of feedback mechanisms of estrogen were considered to be related to hyperprolactinemia itself rather than to sulpiride. Five other normally cycling women received iv injections of 100 microgram LRH on the 22nd day of a cycle under sulpiride-induced hyperprolactinemia since the onset of menstruation. Their mean LH response was somewhat greater (although not statistically significant) and their mean FSH response was considerably greater (P less than 0.001 at all times) than those of a control group of 10 women tested in their luteal phase. The results of these LRH tests under sulpiride-induced hyperprolactinemia give some support to the concept that hyperprolactinemia interferes at the hypothalamic or higher level with cyclic release of indogenous LRH.", "contents": "Alteration of feedback mechanism of estrogen on gonadotropin by sulpiride-induced hyperprolactinemia. Four normally cycling women received an iv injection of 20 mg Premarin (conjugated estrogens equivalent to 20 mg estrone sulfate) on the seventh day of two consecutive cycles; the second experiment was performed under sulpiride-induced hyperprolactinemia (mean PRL level = 906 microU MRC standard 71/222 per ml; significantly 7.8 times greater than mean control level of 115 microU MRC standard 71/222 per ml, P less than 0.001). In comparison to the control experiment, sulpiride-induced hyperprolactinemia prevented the occurrence of any gonadotropin peak within the 84 h of estrogen administration; the negative feedback effect of estrogen on gonadotropin secretion was maintained and was even potentiated. These alterations of feedback mechanisms of estrogen were considered to be related to hyperprolactinemia itself rather than to sulpiride. Five other normally cycling women received iv injections of 100 microgram LRH on the 22nd day of a cycle under sulpiride-induced hyperprolactinemia since the onset of menstruation. Their mean LH response was somewhat greater (although not statistically significant) and their mean FSH response was considerably greater (P less than 0.001 at all times) than those of a control group of 10 women tested in their luteal phase. The results of these LRH tests under sulpiride-induced hyperprolactinemia give some support to the concept that hyperprolactinemia interferes at the hypothalamic or higher level with cyclic release of indogenous LRH."}
{"id": "PMID:233690", "title": "Comparison of absorption of cortisone acetate and hydrocortisone hemisuccinate.", "content": "In four patients who required maintenance glucocorticoid therapy after bilateral adrenalectomy for Cushing's disease, we compared the effects of im injection and oral ingestion of cortisone acetate and hydrocortisone hemisuccinate. By the former route of administration, cortisone acetate was not effective in elevating plasma cortisol levels or in suppressing plasma adrenocorticotropin, although hydrocortisone was. When given by mouth, no significant difference was found between the two steroids. Therefore, in the treatment of acute adrenal insufficiency or in the maintenance of patients with chronic adrenal insufficiency and in their preparation for surgery or other stressful situations, we advise against im injection of cortisone acetate. Oral ingestion, however, is appropriate for maintenance.", "contents": "Comparison of absorption of cortisone acetate and hydrocortisone hemisuccinate. In four patients who required maintenance glucocorticoid therapy after bilateral adrenalectomy for Cushing's disease, we compared the effects of im injection and oral ingestion of cortisone acetate and hydrocortisone hemisuccinate. By the former route of administration, cortisone acetate was not effective in elevating plasma cortisol levels or in suppressing plasma adrenocorticotropin, although hydrocortisone was. When given by mouth, no significant difference was found between the two steroids. Therefore, in the treatment of acute adrenal insufficiency or in the maintenance of patients with chronic adrenal insufficiency and in their preparation for surgery or other stressful situations, we advise against im injection of cortisone acetate. Oral ingestion, however, is appropriate for maintenance."}
{"id": "PMID:233691", "title": "Age-related response of plasma testosterone, delta 4-androstenedione, and cortisol to adrenocorticotropin in infants, children, and adults.", "content": "The response of plasma testosterone (T), delta 4-androstenedione, and cortisol (F) to the administration of synthetic Zn beta 1-24 ACTH (0.5 mg/m2 im every 12 h for 3 days) was ascertained in 20 infants, 35 prepubertal children, 4 early pubertal boys, and 15 adults. At all ages and in both sexes, a significant rise in delta 4-androstenedione and F was observed (P less than 0.00001), whereas the response of T showed a sex difference: T levels increased in females (P less than 0.001) at all ages in response to ACTH, while they decreased (P less than 0.01) in males at periods of active testicular secretion (early infancy, puberty, and adulthood). In prepubertal boys, in the absence of significant Leydig cell activity, T levels increased after ACTH, as they did in girls. The post-ACTH values of T, expressed as percent-ages of the control levels, were significantly lower (P less than 0.01) in infants (3.17 +/- 16.7%) than in pubertal boys (59.5 +/- 14.6%) or adult men (57.9 +/- 7.7%). F levels were significantly higher after ACTH stimulation at 1-4 months of age (253 +/- 129 micrograms/dl) than at any later age studied (64 +/- 17 micrograms/dl). It would seem, therefore, that the suppressive effect of ACTh on testicular secretion might be glucocorticoid mediated and its magnitude might be related to circulating levels of F.", "contents": "Age-related response of plasma testosterone, delta 4-androstenedione, and cortisol to adrenocorticotropin in infants, children, and adults. The response of plasma testosterone (T), delta 4-androstenedione, and cortisol (F) to the administration of synthetic Zn beta 1-24 ACTH (0.5 mg/m2 im every 12 h for 3 days) was ascertained in 20 infants, 35 prepubertal children, 4 early pubertal boys, and 15 adults. At all ages and in both sexes, a significant rise in delta 4-androstenedione and F was observed (P less than 0.00001), whereas the response of T showed a sex difference: T levels increased in females (P less than 0.001) at all ages in response to ACTH, while they decreased (P less than 0.01) in males at periods of active testicular secretion (early infancy, puberty, and adulthood). In prepubertal boys, in the absence of significant Leydig cell activity, T levels increased after ACTH, as they did in girls. The post-ACTH values of T, expressed as percent-ages of the control levels, were significantly lower (P less than 0.01) in infants (3.17 +/- 16.7%) than in pubertal boys (59.5 +/- 14.6%) or adult men (57.9 +/- 7.7%). F levels were significantly higher after ACTH stimulation at 1-4 months of age (253 +/- 129 micrograms/dl) than at any later age studied (64 +/- 17 micrograms/dl). It would seem, therefore, that the suppressive effect of ACTh on testicular secretion might be glucocorticoid mediated and its magnitude might be related to circulating levels of F."}
{"id": "PMID:233692", "title": "Circulating parathyroid hormone activity: familial hypocalciuric hypercalcemia versus typical primary hyperparathyroidism.", "content": "Three indices of circulating parathyroid hormone (PTH) activity were compared between two groups: the first a group of 23 patients from three large kindreds with autosomal dominant hypercalcemia without hypercalciuria [familial hypocalciuric hypercalcemia (FHH)] and the second a group of 64 patients with typical primary hyperparathyroidism (1HPT) manifesting comparable hypercalcemia. The group with 1HPT differed from normal with respect to plasma PTH 1HPT concentration (normal, less 0.2 ng/ml), urinary cAMP excretion per 100 ml glomerular filtrate (U cAMP/GF) (normal, 2.3 x/divided by 0.6 nmol/100 ml glomerular filtrate; mean, x/divided 1 SD), and renal tubular maximum of phosphate transport corrected for glomerular filtration rate (TMP/GFR; normal, 3.4 +/- 0.4 mg/dl; mean, +/- 1 SD). The group with 1HPT also diverged significantly from the group with FHH for all three indices: for PTH, 0.37 x/divided by .48 vs. 0.25 x/divided .46 (P less than 0.05); for UcAMP/GF, 4.3 x/divided by .53 vs. 2.6 x/divided .60 (P less than 0.0005); and for TMP/GFR, 2.0 +/- 0.6 vs. 2.6 +/- 0.7 (P less than 0.01). The between-group differences for all three indices were also significant after adjustment for their variation with serum calcium. However, only the difference in TMP/GFR remained significant after adjustment for covariance attributable to serum calcium concentration, age, and creatinine clearance. The group with FHH differed from normal for TMP/GFR but not for UcAMP/GF. However, analysis of changes in UcAMP/GF and serum calcium concentration around the time of parathyroidectomy in three patients with FHH suggested that the parathyroid glands contributed to the abnormalities of mineral homeostasis in at least one. It was concluded that higher serum concentrations of PTH do not account for the lower renal clearance of calcium and magnesium in FHH calcium concentration, the group with FHH showed indices suggesting lower circulating PTH activity than the group with 1HPT.", "contents": "Circulating parathyroid hormone activity: familial hypocalciuric hypercalcemia versus typical primary hyperparathyroidism. Three indices of circulating parathyroid hormone (PTH) activity were compared between two groups: the first a group of 23 patients from three large kindreds with autosomal dominant hypercalcemia without hypercalciuria [familial hypocalciuric hypercalcemia (FHH)] and the second a group of 64 patients with typical primary hyperparathyroidism (1HPT) manifesting comparable hypercalcemia. The group with 1HPT differed from normal with respect to plasma PTH 1HPT concentration (normal, less 0.2 ng/ml), urinary cAMP excretion per 100 ml glomerular filtrate (U cAMP/GF) (normal, 2.3 x/divided by 0.6 nmol/100 ml glomerular filtrate; mean, x/divided 1 SD), and renal tubular maximum of phosphate transport corrected for glomerular filtration rate (TMP/GFR; normal, 3.4 +/- 0.4 mg/dl; mean, +/- 1 SD). The group with 1HPT also diverged significantly from the group with FHH for all three indices: for PTH, 0.37 x/divided by .48 vs. 0.25 x/divided .46 (P less than 0.05); for UcAMP/GF, 4.3 x/divided by .53 vs. 2.6 x/divided .60 (P less than 0.0005); and for TMP/GFR, 2.0 +/- 0.6 vs. 2.6 +/- 0.7 (P less than 0.01). The between-group differences for all three indices were also significant after adjustment for their variation with serum calcium. However, only the difference in TMP/GFR remained significant after adjustment for covariance attributable to serum calcium concentration, age, and creatinine clearance. The group with FHH differed from normal for TMP/GFR but not for UcAMP/GF. However, analysis of changes in UcAMP/GF and serum calcium concentration around the time of parathyroidectomy in three patients with FHH suggested that the parathyroid glands contributed to the abnormalities of mineral homeostasis in at least one. It was concluded that higher serum concentrations of PTH do not account for the lower renal clearance of calcium and magnesium in FHH calcium concentration, the group with FHH showed indices suggesting lower circulating PTH activity than the group with 1HPT."}
{"id": "PMID:233693", "title": "The effect of long acting glucocorticoids on menstrual abnormalities in patients with virilizing congenital adrenal hyperplasia.", "content": "Amenorrhea or oligomenorrhea occurs in more than 25% of young women with virilizing congenital adrenal hyperplasia due to 21-hydroxylase deficiency who are treated with conventional glucocorticoid therapy. In four such patients, we studied the variation in plasma concentration of ACTH, 17-hydroxyprogesterone (17-OHP), estradiol (E2), estrone, testosterone (T), dehydroepiandrosterone and its sulfate, androstenedione, and progesterone before and at frequent intervals after the administration of the patients' usual dose of oral glucocorticoids. We found that plasma ACTH, 17-OHP, and T were usually increased above the normal range early in the morning before the first daily dose of medication; plasma dehydroepiandrosterone and its sulfate were decreased below the normal range for the patient's pubertal stage; and androstenedione, estrone, and E2 were within the normal range. Two of the four patients had low basal plasma LH and impaired LH response to LRF. Administration of a long acting glucocorticoid (dexamethasone) to three patients, and methylprednisolone to one, resulted in continuous suppression of T into the normal range in all patients, in spite of continued abnormally increased concentration of ACTH and 17-OHP in two patients. In three patients, E2 concentrations were increased when a long acting glucocorticoid was given. In all four patients, menses began or became more regular during treatment with the long acting glucocorticoid. We conclude that a long acting glucocorticoid is useful in the management of menstrual abnormalities in adolescent patients with congenital adrenal hyperplasia  who have attained their adult height, and that monitoring the concentration of serum T in them is a valuable but not infallible procedure for assessing the effectiveness of therapy.", "contents": "The effect of long acting glucocorticoids on menstrual abnormalities in patients with virilizing congenital adrenal hyperplasia. Amenorrhea or oligomenorrhea occurs in more than 25% of young women with virilizing congenital adrenal hyperplasia due to 21-hydroxylase deficiency who are treated with conventional glucocorticoid therapy. In four such patients, we studied the variation in plasma concentration of ACTH, 17-hydroxyprogesterone (17-OHP), estradiol (E2), estrone, testosterone (T), dehydroepiandrosterone and its sulfate, androstenedione, and progesterone before and at frequent intervals after the administration of the patients' usual dose of oral glucocorticoids. We found that plasma ACTH, 17-OHP, and T were usually increased above the normal range early in the morning before the first daily dose of medication; plasma dehydroepiandrosterone and its sulfate were decreased below the normal range for the patient's pubertal stage; and androstenedione, estrone, and E2 were within the normal range. Two of the four patients had low basal plasma LH and impaired LH response to LRF. Administration of a long acting glucocorticoid (dexamethasone) to three patients, and methylprednisolone to one, resulted in continuous suppression of T into the normal range in all patients, in spite of continued abnormally increased concentration of ACTH and 17-OHP in two patients. In three patients, E2 concentrations were increased when a long acting glucocorticoid was given. In all four patients, menses began or became more regular during treatment with the long acting glucocorticoid. We conclude that a long acting glucocorticoid is useful in the management of menstrual abnormalities in adolescent patients with congenital adrenal hyperplasia  who have attained their adult height, and that monitoring the concentration of serum T in them is a valuable but not infallible procedure for assessing the effectiveness of therapy."}
{"id": "PMID:233694", "title": "Abnormalities of triiodothyronine binding to lymphocyte and fibroblast nuclei from a patient with peripheral tissue resistance to thyroid hormone action.", "content": "T3 binding to lymphocyte nuclei has been studied in normal individuals and in a patient (MaG) with peripheral resistance to thyroid hormone action. This syndrome is defined by the presence of hypothyroidism or euthyroidism with high plasma levels of thyroid hormone. T3 bound to a single set of binding sites in normal adult lymphocyte nuclei with a mean Ka of 8.9 +/- 7.1 x 109 M-1, and a capacity of 4.4 +/- 2.9 fmol/100 micrograms DNA. A single binding site was also disclosed in MaG's lymphocytes with a Ka of 0.43 x 109 M-1 and a capacity of 10.5 fmol/100 micrograms DNA. This low affinity was not due to the presence of high plasma T3 level in the patient, since administration of 100 micrograms T3 to normal adult volunteers induced the presence of two different binding sites. The mechanism responsible for this phenomenon is unknown. To binding was also studied using cultured fibroblasts which were incubated in serum-less medium before the binding experiments. One single binding site (Ka, 1.9 x 10(10) M-1, capacity, 12.9 fmol/100 micrograms DNA) was detected in normal fibroblast nuclei. In contrast, a curvilinear Scatchard plot was obtained when MaG's fibroblasts were used. This result could be compatible with the presence of either two different binding sites or negative cooperativity. In support of the latter possibility, Hill plots gave a number lower than unity. The results suggest that the syndrome of peripheral tissue resistance to thyroid hormone action due to a defect at the level of the nuclear receptor. The possible existence of similar syndromes due to an alteration at the level of a post-T3-binding mechanism is not eliminated.", "contents": "Abnormalities of triiodothyronine binding to lymphocyte and fibroblast nuclei from a patient with peripheral tissue resistance to thyroid hormone action. T3 binding to lymphocyte nuclei has been studied in normal individuals and in a patient (MaG) with peripheral resistance to thyroid hormone action. This syndrome is defined by the presence of hypothyroidism or euthyroidism with high plasma levels of thyroid hormone. T3 bound to a single set of binding sites in normal adult lymphocyte nuclei with a mean Ka of 8.9 +/- 7.1 x 109 M-1, and a capacity of 4.4 +/- 2.9 fmol/100 micrograms DNA. A single binding site was also disclosed in MaG's lymphocytes with a Ka of 0.43 x 109 M-1 and a capacity of 10.5 fmol/100 micrograms DNA. This low affinity was not due to the presence of high plasma T3 level in the patient, since administration of 100 micrograms T3 to normal adult volunteers induced the presence of two different binding sites. The mechanism responsible for this phenomenon is unknown. To binding was also studied using cultured fibroblasts which were incubated in serum-less medium before the binding experiments. One single binding site (Ka, 1.9 x 10(10) M-1, capacity, 12.9 fmol/100 micrograms DNA) was detected in normal fibroblast nuclei. In contrast, a curvilinear Scatchard plot was obtained when MaG's fibroblasts were used. This result could be compatible with the presence of either two different binding sites or negative cooperativity. In support of the latter possibility, Hill plots gave a number lower than unity. The results suggest that the syndrome of peripheral tissue resistance to thyroid hormone action due to a defect at the level of the nuclear receptor. The possible existence of similar syndromes due to an alteration at the level of a post-T3-binding mechanism is not eliminated."}
{"id": "PMID:233695", "title": "A familial syndrome of decrease in sensitivity to 1,25-dihydroxyvitamin D.", "content": "Typical features of hereditary vitamin D-dependent (pseudovitamin D-deficient) rickets were observed beginning at ages 20 and 5 months in a brother and sister. Both had calcium malabsorption correctable with high doses of 25-hydroxyvitamin D. During periods of hypocalcemia they both manifested secondary hyperparathyroidism with hypophosphatemia and high serum concentrations of endogenously produced 1,25-dihydroxyvitamin D. In each, normalization of serum calcium concentration and resolution of osteomalacia were obtained with continuous administration of high doses of ergocalciferol or high doses of 1,25-dihydroxycholecalciferol. Chemical features of vitamin D deficiency were corrected in the presence of high circulating concentrations of 1,25-dihydroxyvitamin D2, produced endogenously, or of 1,25-dihydroxyvitamin D3, administered by mouth. Serum concentrations of 25-hydroxyvitamin D2, 25-hydroxyvitamin D3, 24,25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D were normal in five first degree relatives. We conclude that in these five first degree relatives. We conclude that in these siblings, rickets and osteomalacia resulted from a hereditary decreased sensitivity to 1,25-dihydroxyvitamin D at the intestine and perhaps other vitamin D target tissues.", "contents": "A familial syndrome of decrease in sensitivity to 1,25-dihydroxyvitamin D. Typical features of hereditary vitamin D-dependent (pseudovitamin D-deficient) rickets were observed beginning at ages 20 and 5 months in a brother and sister. Both had calcium malabsorption correctable with high doses of 25-hydroxyvitamin D. During periods of hypocalcemia they both manifested secondary hyperparathyroidism with hypophosphatemia and high serum concentrations of endogenously produced 1,25-dihydroxyvitamin D. In each, normalization of serum calcium concentration and resolution of osteomalacia were obtained with continuous administration of high doses of ergocalciferol or high doses of 1,25-dihydroxycholecalciferol. Chemical features of vitamin D deficiency were corrected in the presence of high circulating concentrations of 1,25-dihydroxyvitamin D2, produced endogenously, or of 1,25-dihydroxyvitamin D3, administered by mouth. Serum concentrations of 25-hydroxyvitamin D2, 25-hydroxyvitamin D3, 24,25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D were normal in five first degree relatives. We conclude that in these five first degree relatives. We conclude that in these siblings, rickets and osteomalacia resulted from a hereditary decreased sensitivity to 1,25-dihydroxyvitamin D at the intestine and perhaps other vitamin D target tissues."}
{"id": "PMID:233696", "title": "Ectopic production of high molecular weight calcitonin and corticotropin by human small cell carcinoma cells in tissue culture: evidence for separate precursors.", "content": "The DMS-79 continuous line of human small cell lung carcinoma cells, which produces immunoreactive (IR)-corticotropin (ACTH), -lipotropin (LPH), and -beta-endorphin (beta END), was found to produce IR-calcitonin (CT). Two major high molecular weight (HMW) forms of IR-CT were observed after gel exclusion chromatography under denaturing conditions (mol wt. approximately 7,000 and approximately 14,000), as well as a minor HMW IR-CT component (mol. wt. approximately 70,000). None of these IR-CT materials was extracted from DMS-79 medium by affinity chromatography using an ACTH antibody covalently bound to agarose. These results demonstrate ectopic production of HMW forms of CT and ACTH/LPH/beta END by human lung tumor cells in tissue culture, but do not support the existence of a common CT/ACTH/LPH/beta END precursor molecule.", "contents": "Ectopic production of high molecular weight calcitonin and corticotropin by human small cell carcinoma cells in tissue culture: evidence for separate precursors. The DMS-79 continuous line of human small cell lung carcinoma cells, which produces immunoreactive (IR)-corticotropin (ACTH), -lipotropin (LPH), and -beta-endorphin (beta END), was found to produce IR-calcitonin (CT). Two major high molecular weight (HMW) forms of IR-CT were observed after gel exclusion chromatography under denaturing conditions (mol wt. approximately 7,000 and approximately 14,000), as well as a minor HMW IR-CT component (mol. wt. approximately 70,000). None of these IR-CT materials was extracted from DMS-79 medium by affinity chromatography using an ACTH antibody covalently bound to agarose. These results demonstrate ectopic production of HMW forms of CT and ACTH/LPH/beta END by human lung tumor cells in tissue culture, but do not support the existence of a common CT/ACTH/LPH/beta END precursor molecule."}
{"id": "PMID:233697", "title": "Studies on platelet aggregation inhibitors in vivo. VIII. Effect of pentoxifylline on spontaneous tumor metastasis.", "content": "Pentoxifylline (Trental), a phosphodiesterase inhibitor with platelet aggregation inhibitory effect, was shown to decrease spontaneous metastases in a Wilms' tumor model in Furth-Wistar rats and in neuroblastoma C1300 in A/J mice. It was ineffective in the NIH renal adenocarcinoma in BALB/cCr mice.", "contents": "Studies on platelet aggregation inhibitors in vivo. VIII. Effect of pentoxifylline on spontaneous tumor metastasis. Pentoxifylline (Trental), a phosphodiesterase inhibitor with platelet aggregation inhibitory effect, was shown to decrease spontaneous metastases in a Wilms' tumor model in Furth-Wistar rats and in neuroblastoma C1300 in A/J mice. It was ineffective in the NIH renal adenocarcinoma in BALB/cCr mice."}
{"id": "PMID:233699", "title": "Niemann-Pick disease: prenatal diagnoses and studies of sphingomyelinase activities.", "content": "Five pregnancies were monitored for couples at-risk for having a child with some form of Niemann-Pick disease (NPD). Three of these were for the classic Type A form in which affected children usually have less than 1% of normal sphingomyelinase activity. Two of these pregnancies were terminated after the cultured amniotic-fluid cells were determined to have less than 1% of normal sphingomyelinase activity (0.4 and 0.6 nmole/mg protein/hr versus the control mean of 61.7). In the other pregnancy at risk for Type A NPD near normal activity was measured and it was continued to term. The two other pregnancies were monitored for couples in which severely affected children were found to have partially deficient sphingomyelinase activity (about 20% of normal) in cultured skin fibroblasts. Cultural amniotic-fluid cells from one of these pregnancies also had about 20% of control sphingomyelinase activity, but the woman underwent a spontaneous abortion soon after the cells were received and no studies on the fetus were done. The other sample was taken at the time of abortion for social reasons. In this case the cultured amniotic-fluid cells and cultured fetal skin fibroblasts gave normal sphingomyelinase activity. Enzymatic studies on tissues from the two fetuses predicted to be affected with Type A NPD confirmed the prenatal diagnosis. Studies of sphingomyelinase activity in the brains from these fetuses and from a child who died with Type A NPD indicated significant levels of activity when measured at pH 7.4 in the presence of magnesium. The higher level of the pH 7.4 sphingomyelinase activity in developing brain may indicate some important role in normal brain development.", "contents": "Niemann-Pick disease: prenatal diagnoses and studies of sphingomyelinase activities. Five pregnancies were monitored for couples at-risk for having a child with some form of Niemann-Pick disease (NPD). Three of these were for the classic Type A form in which affected children usually have less than 1% of normal sphingomyelinase activity. Two of these pregnancies were terminated after the cultured amniotic-fluid cells were determined to have less than 1% of normal sphingomyelinase activity (0.4 and 0.6 nmole/mg protein/hr versus the control mean of 61.7). In the other pregnancy at risk for Type A NPD near normal activity was measured and it was continued to term. The two other pregnancies were monitored for couples in which severely affected children were found to have partially deficient sphingomyelinase activity (about 20% of normal) in cultured skin fibroblasts. Cultural amniotic-fluid cells from one of these pregnancies also had about 20% of control sphingomyelinase activity, but the woman underwent a spontaneous abortion soon after the cells were received and no studies on the fetus were done. The other sample was taken at the time of abortion for social reasons. In this case the cultured amniotic-fluid cells and cultured fetal skin fibroblasts gave normal sphingomyelinase activity. Enzymatic studies on tissues from the two fetuses predicted to be affected with Type A NPD confirmed the prenatal diagnosis. Studies of sphingomyelinase activity in the brains from these fetuses and from a child who died with Type A NPD indicated significant levels of activity when measured at pH 7.4 in the presence of magnesium. The higher level of the pH 7.4 sphingomyelinase activity in developing brain may indicate some important role in normal brain development."}
{"id": "PMID:233700", "title": "Pseudohypoparathyroidism and idiopathic hypoparathyroidism: relationship between serum calcium and parathyroid hormone levels and urinary cyclic adenosine-3',5'-monophosphate response to parathyroid extract.", "content": "Forty patients with hypocalcemia and/or Albright's hereditary osteodystrophy were studied. Based on the estimation of serum calcium and parathyroid hormone (PTH) levels as well as the urinary cAMP response to infusions with parathyroid extract, it was possible to classify all of the patients studied as cases with idiopathic hypoparathyroidism (n = 6, low PTH, normal cAMP response), pseudohypoparathyroidism (PHP) type I (n = 18, high PTH, low cAMP response) and type II (n = 2, high PTH, normal cAMP response), as well as pseudopseudohypoparathyroidism (n = 14, normal PTH, normal cAMP response). In three cases studied at the age of 12, 17, and 23 yr, the signs of Albright's hereditary osteodystrophy were not observed. PTH levels were unusually high for a given serum calcium concentration in some patients with PHP, the increased PTH levels were, however, normalized during iv calcium infusions. In two young children with PHP, a gradual increase of serum PTH levels occurred despite persistent normocalcemia over a period of 3 yr. This suggests that factors other than hypocalcemia or frequent small unobservable falls of the serum calcium concentration, such as a deficient formation of 1,25-dihydroxyvitamin D3, secretion of an abnormal PTH, or an abnormal metabolism of the hormone, may contribute to the secondary hyperparathyroidism in PHP.", "contents": "Pseudohypoparathyroidism and idiopathic hypoparathyroidism: relationship between serum calcium and parathyroid hormone levels and urinary cyclic adenosine-3',5'-monophosphate response to parathyroid extract. Forty patients with hypocalcemia and/or Albright's hereditary osteodystrophy were studied. Based on the estimation of serum calcium and parathyroid hormone (PTH) levels as well as the urinary cAMP response to infusions with parathyroid extract, it was possible to classify all of the patients studied as cases with idiopathic hypoparathyroidism (n = 6, low PTH, normal cAMP response), pseudohypoparathyroidism (PHP) type I (n = 18, high PTH, low cAMP response) and type II (n = 2, high PTH, normal cAMP response), as well as pseudopseudohypoparathyroidism (n = 14, normal PTH, normal cAMP response). In three cases studied at the age of 12, 17, and 23 yr, the signs of Albright's hereditary osteodystrophy were not observed. PTH levels were unusually high for a given serum calcium concentration in some patients with PHP, the increased PTH levels were, however, normalized during iv calcium infusions. In two young children with PHP, a gradual increase of serum PTH levels occurred despite persistent normocalcemia over a period of 3 yr. This suggests that factors other than hypocalcemia or frequent small unobservable falls of the serum calcium concentration, such as a deficient formation of 1,25-dihydroxyvitamin D3, secretion of an abnormal PTH, or an abnormal metabolism of the hormone, may contribute to the secondary hyperparathyroidism in PHP."}
{"id": "PMID:233701", "title": "Diurnal rhythm and disappearance half-time of endogenous plasma immunoreactive beta-MSH (LPH) and ACTH in man.", "content": "In order first to establish the disappearance t 1/2 of endogenous immunoreactive human beta-MSH (RIA-h beta MSH), which is now known to represent the lipotropins, human beta-LPH and human gamma-LPH, the plasma concentrations of RIA-h beta MSH, RIA-hACTH, and fluorogenic corticosteroids (cortisol) were measured before and during infusion of cortisol in three patients with primary adrenocortical insufficiency from whom steroid replacement had been withdrawn. The t 1/2 for RIA-h beta MSH ranged from 44-133 min (mean, 83), and for RIA-hACTH ranged from 20-51 min (mean, 40). On this basis, 30-min sampling intervals were chosen to measure plasma concentrations of RIA-h beta MSH, RIA-hACTH, and cortisol in three normal subjects for 24 h. Similar diurnal rhythms were observed for all three hormones. Highest values (58.0 +/- 5.8 pg/ml) for RIA-h beta MSH were observed at about the time of awaking and lowest values (15.0 +/- 2.1 pg/ml) shortly after retiring. The secretion of both RIA-h beta MSH and RIA-hACTH appeared to be episodic, with about 8-10 secretory episodes/24 h, and the timing of their secretory episodes appeared to be nearly identical. There was excellent correlation (P less than 0.001) between simultaneous concentrations of RIA-h beta MSH and RIA-hACTH in all three subjects. These results establish the presence of a diurnal rhythm in plasma lipotropins (RIA-h beta MSH) and suggest that roughly equimolar amounts of ACTH and LPH are secreted simultaneously by the pituitary under basal conditions in man.", "contents": "Diurnal rhythm and disappearance half-time of endogenous plasma immunoreactive beta-MSH (LPH) and ACTH in man. In order first to establish the disappearance t 1/2 of endogenous immunoreactive human beta-MSH (RIA-h beta MSH), which is now known to represent the lipotropins, human beta-LPH and human gamma-LPH, the plasma concentrations of RIA-h beta MSH, RIA-hACTH, and fluorogenic corticosteroids (cortisol) were measured before and during infusion of cortisol in three patients with primary adrenocortical insufficiency from whom steroid replacement had been withdrawn. The t 1/2 for RIA-h beta MSH ranged from 44-133 min (mean, 83), and for RIA-hACTH ranged from 20-51 min (mean, 40). On this basis, 30-min sampling intervals were chosen to measure plasma concentrations of RIA-h beta MSH, RIA-hACTH, and cortisol in three normal subjects for 24 h. Similar diurnal rhythms were observed for all three hormones. Highest values (58.0 +/- 5.8 pg/ml) for RIA-h beta MSH were observed at about the time of awaking and lowest values (15.0 +/- 2.1 pg/ml) shortly after retiring. The secretion of both RIA-h beta MSH and RIA-hACTH appeared to be episodic, with about 8-10 secretory episodes/24 h, and the timing of their secretory episodes appeared to be nearly identical. There was excellent correlation (P less than 0.001) between simultaneous concentrations of RIA-h beta MSH and RIA-hACTH in all three subjects. These results establish the presence of a diurnal rhythm in plasma lipotropins (RIA-h beta MSH) and suggest that roughly equimolar amounts of ACTH and LPH are secreted simultaneously by the pituitary under basal conditions in man."}
{"id": "PMID:233702", "title": "Cell-free translation of messenger RNA extracted from a human insulinoma.", "content": "Total nucleic acid has been extracted from a human pancreatic insulinoma. Purification of the messenger RNA (mRNA) fraction by oligo-dT cellulose chromatography yielded 200 micrograms poly(A)-rich mRNA. This mRNA produced a 2-fold stimulation of protein synthesis in a wheat germ cell-free system. Analysis of the translation products by gel filtration chromatography (Biogel P-30) revealed nothing smaller than an acid-alcohol-soluble protein larger than bovine proinsulin. In contrast, insulinoma slices incubated with labeled amino acids synthesized smaller proteins which comigrated with bovine proinsulin and insulin. [3H]Leucine-labeled cell-free proteins were electrophoresed on NaDodSO4-urea polyacrylamide slab gels. In the presence of insulinoma mRNA, discrete proteins of 25,000 and 11,500 mol wt were synthesized. The 11,500 mol wt protein was specifically immunoprecipitated with antiinsulin serum. Thus, cell-free translation of human insulinoma mRNA yields an immunoreactive insulin larger than proinsulin, which is the same size as fish and rat preproinsulins recently described.", "contents": "Cell-free translation of messenger RNA extracted from a human insulinoma. Total nucleic acid has been extracted from a human pancreatic insulinoma. Purification of the messenger RNA (mRNA) fraction by oligo-dT cellulose chromatography yielded 200 micrograms poly(A)-rich mRNA. This mRNA produced a 2-fold stimulation of protein synthesis in a wheat germ cell-free system. Analysis of the translation products by gel filtration chromatography (Biogel P-30) revealed nothing smaller than an acid-alcohol-soluble protein larger than bovine proinsulin. In contrast, insulinoma slices incubated with labeled amino acids synthesized smaller proteins which comigrated with bovine proinsulin and insulin. [3H]Leucine-labeled cell-free proteins were electrophoresed on NaDodSO4-urea polyacrylamide slab gels. In the presence of insulinoma mRNA, discrete proteins of 25,000 and 11,500 mol wt were synthesized. The 11,500 mol wt protein was specifically immunoprecipitated with antiinsulin serum. Thus, cell-free translation of human insulinoma mRNA yields an immunoreactive insulin larger than proinsulin, which is the same size as fish and rat preproinsulins recently described."}
{"id": "PMID:233704", "title": "A method for determining bone mineral content using Fourier image reconstruction and dual source technique.", "content": "The basic principles of a quantitative tomographic technique for bone mineral determination are considered. The bone mineral content could be evaluated from a single reconstruction using projection data from two different energies. Beam hardening effects and photon counting statistics are studied by computer simulation and found to be the limiting factors in precision and accuracy.", "contents": "A method for determining bone mineral content using Fourier image reconstruction and dual source technique. The basic principles of a quantitative tomographic technique for bone mineral determination are considered. The bone mineral content could be evaluated from a single reconstruction using projection data from two different energies. Beam hardening effects and photon counting statistics are studied by computer simulation and found to be the limiting factors in precision and accuracy."}
{"id": "PMID:233705", "title": "Computed tomographic demonstration of inferior vena cava invasion in a case of hepatocellular carcinoma.", "content": "A case of hepatocellular carcinoma with neoplastic invasion of the inferior vena cava is presented. Computed tomograms before and after injection of contrast medium revealed an unusual density enhancement of the wall of the invaded portion of the vena cava. This sign is correlated with an angiographic sign of venous invasion present in our case.", "contents": "Computed tomographic demonstration of inferior vena cava invasion in a case of hepatocellular carcinoma. A case of hepatocellular carcinoma with neoplastic invasion of the inferior vena cava is presented. Computed tomograms before and after injection of contrast medium revealed an unusual density enhancement of the wall of the invaded portion of the vena cava. This sign is correlated with an angiographic sign of venous invasion present in our case."}
{"id": "PMID:233706", "title": "[Morphological characteristics and the degree of somatic maturity in children of short stature].", "content": "An auxological investigation involved 199 children with short stature ( hypostatura simplex) in preschool and school age. The analysis of the material showed that eight anthropometrical patterns and five somatometric indices, with the evaluation of the level of skeletal maturity, were all lower in children under study in comparison to the mean growth standard for Warsaw children. In all features differences were statistically significant. The biggest differences however, were found in the length of the upper extremities and the trunk. Observed differences increase with age. The authors concluded that the children under study were harmoniously delayed in morphological age which was confirmed by the level of the index of biological maturity based on skeletal age. It was found that the level of biological maturation was delayed but not to such a great extent as in growth pathology.", "contents": "[Morphological characteristics and the degree of somatic maturity in children of short stature]. An auxological investigation involved 199 children with short stature ( hypostatura simplex) in preschool and school age. The analysis of the material showed that eight anthropometrical patterns and five somatometric indices, with the evaluation of the level of skeletal maturity, were all lower in children under study in comparison to the mean growth standard for Warsaw children. In all features differences were statistically significant. The biggest differences however, were found in the length of the upper extremities and the trunk. Observed differences increase with age. The authors concluded that the children under study were harmoniously delayed in morphological age which was confirmed by the level of the index of biological maturity based on skeletal age. It was found that the level of biological maturation was delayed but not to such a great extent as in growth pathology."}
{"id": "PMID:233708", "title": "[Bilateral nephroblastoma in children].", "content": "The rarity of such form of nephroblastoma containing about 4% among embryonal renal tumors in this paper, was the subject of special attention. The necessity of preoperative differential diagnosis particularly in cases of congenital multicystic kidney, congenital hydronephrosis and retroperitoneal sympathetic neoplasms was stressed. Radiological investigation facilitate distinguishing of the three pathological forms. A multicystic degeneration of kidney is usually bilateral and it includes both the medulla and the renal cortex. The cystic patterns nearly equal in size are multiple and minute. In the bilateral Wilms' tumour besides the kidney enlargement there are deformations such as hydrocalyx , hydronephrosis or modeling signs. In case of congenital hydronephrosis the kidney keeps the same size and produces the thinner cortex zone. The neoplasms of the sympathetic nerve origin produce first the displacement of kidney and then the deformation of pelvico -calyceal system with modeling signs and sometimes with hydronephrosis. In the above mentioned entities, late urographical pictures are of great significance. The angiographic investigations of kidney play a very important part in the differential diagnosis and planning of operative procedures. The nephrographic phase of angiography shows the quantity and location of active renal parenchyma. A renal arteriography is also important in the evaluation of the applied therapy, particularly in case of multistage therapeutic procedures.", "contents": "[Bilateral nephroblastoma in children]. The rarity of such form of nephroblastoma containing about 4% among embryonal renal tumors in this paper, was the subject of special attention. The necessity of preoperative differential diagnosis particularly in cases of congenital multicystic kidney, congenital hydronephrosis and retroperitoneal sympathetic neoplasms was stressed. Radiological investigation facilitate distinguishing of the three pathological forms. A multicystic degeneration of kidney is usually bilateral and it includes both the medulla and the renal cortex. The cystic patterns nearly equal in size are multiple and minute. In the bilateral Wilms' tumour besides the kidney enlargement there are deformations such as hydrocalyx , hydronephrosis or modeling signs. In case of congenital hydronephrosis the kidney keeps the same size and produces the thinner cortex zone. The neoplasms of the sympathetic nerve origin produce first the displacement of kidney and then the deformation of pelvico -calyceal system with modeling signs and sometimes with hydronephrosis. In the above mentioned entities, late urographical pictures are of great significance. The angiographic investigations of kidney play a very important part in the differential diagnosis and planning of operative procedures. The nephrographic phase of angiography shows the quantity and location of active renal parenchyma. A renal arteriography is also important in the evaluation of the applied therapy, particularly in case of multistage therapeutic procedures."}
{"id": "PMID:233709", "title": "Supersensitivity to norepinephrine or dopamine antagonists after knife cuts that produce aphagia and adipsia in rats.", "content": "Aphagia and adipsia of equivalent duration were produced by knife cuts along the lateral border of the hypothalamus (PH cuts), or the medial surface of the globus pallidus (MP cuts) in male albino rats. Striatal dopamine (DA) was reduced by 75% in animals with PH cuts but only 50% by MP cuts. Hypothalamic norepinephrine was reduced 25% by PH cuts and was unaffected by MP cuts. Aphagia and adipsia were positively correlated with DA depletions only in rats with PH cuts. Presurgical catecholamine depletions produced by chronic injections of alpha-methyl-p-tyrosine did not alter the duration of aphagia or adipsia resulting from these knife cuts. However, following recovery of ingestive behavior, rats with PH and MP cuts were supersensitive to the anorexic effects of the dopamine-beta-hydroxylase inhibitor, diethyldithiocarbamate. Exaggerated anorexia was also observed after DA blockade by haloperidol or alpha-adrenergic blockade by phenoxybenzamine. The most pronounced effects of catecholamine blockade were observed in rats with PH cuts.", "contents": "Supersensitivity to norepinephrine or dopamine antagonists after knife cuts that produce aphagia and adipsia in rats. Aphagia and adipsia of equivalent duration were produced by knife cuts along the lateral border of the hypothalamus (PH cuts), or the medial surface of the globus pallidus (MP cuts) in male albino rats. Striatal dopamine (DA) was reduced by 75% in animals with PH cuts but only 50% by MP cuts. Hypothalamic norepinephrine was reduced 25% by PH cuts and was unaffected by MP cuts. Aphagia and adipsia were positively correlated with DA depletions only in rats with PH cuts. Presurgical catecholamine depletions produced by chronic injections of alpha-methyl-p-tyrosine did not alter the duration of aphagia or adipsia resulting from these knife cuts. However, following recovery of ingestive behavior, rats with PH and MP cuts were supersensitive to the anorexic effects of the dopamine-beta-hydroxylase inhibitor, diethyldithiocarbamate. Exaggerated anorexia was also observed after DA blockade by haloperidol or alpha-adrenergic blockade by phenoxybenzamine. The most pronounced effects of catecholamine blockade were observed in rats with PH cuts."}
{"id": "PMID:233710", "title": "Debilitating interaction of adrenalectomy and intrahypothalamic implants of prostaglandin E2 upon open-field activity levels and sexual receptivity in estrogen-primed ovariectomized rats.", "content": "A group of estrogen-primed, ovariectomized rats was adrenalectomized and tested for sexual receptivity following hypothalamic implantations of PGE2. The combination of PGE2 and adrenalectomy led to severe debilitation as manifested by greatly reduced open-field activity scores and inhibition of estrogen and progesterone induced sexual receptivity. Neither exogenous progesterone nor corticosterone was able to restore these behaviors to normal levels. A mechanism involving PGE2 and adrenalectomy-induced transient ischemia was discussed as a possible cause of the debilitation.", "contents": "Debilitating interaction of adrenalectomy and intrahypothalamic implants of prostaglandin E2 upon open-field activity levels and sexual receptivity in estrogen-primed ovariectomized rats. A group of estrogen-primed, ovariectomized rats was adrenalectomized and tested for sexual receptivity following hypothalamic implantations of PGE2. The combination of PGE2 and adrenalectomy led to severe debilitation as manifested by greatly reduced open-field activity scores and inhibition of estrogen and progesterone induced sexual receptivity. Neither exogenous progesterone nor corticosterone was able to restore these behaviors to normal levels. A mechanism involving PGE2 and adrenalectomy-induced transient ischemia was discussed as a possible cause of the debilitation."}
{"id": "PMID:233711", "title": "(-)-Hydroxycitrate and conditioned aversions.", "content": "The capacity of various salts of (-)-hydroxycitrate to produce conditioned rejection of a 0.25% saccharin solution was evaluated. The ethylenediamine salt of (-)-hydroxycitrate produced strong conditioned rejection of saccharin under both deprivation and nondeprivation conditions, but this effect was less than produced by equimolar doses of lithium chloride. The sodium salt of hydroxycitrate produced no conditioned rejection of saccharin in water deprived rats but did so in nondeprived animals. In these experiments, food intake was reduced by (-)-hydroxycitrate only during the first hour following administration of the drug. The magnitude of appetite rejection did not correspond to the degree of conditioned rejection, lending support to the conclusion that the food intake reduction was not merely a consequence of aversive effects of the drug.", "contents": "(-)-Hydroxycitrate and conditioned aversions. The capacity of various salts of (-)-hydroxycitrate to produce conditioned rejection of a 0.25% saccharin solution was evaluated. The ethylenediamine salt of (-)-hydroxycitrate produced strong conditioned rejection of saccharin under both deprivation and nondeprivation conditions, but this effect was less than produced by equimolar doses of lithium chloride. The sodium salt of hydroxycitrate produced no conditioned rejection of saccharin in water deprived rats but did so in nondeprived animals. In these experiments, food intake was reduced by (-)-hydroxycitrate only during the first hour following administration of the drug. The magnitude of appetite rejection did not correspond to the degree of conditioned rejection, lending support to the conclusion that the food intake reduction was not merely a consequence of aversive effects of the drug."}
{"id": "PMID:233712", "title": "The aftercare clinic as a residency training site. 'Community neuropsychiatry'.", "content": "Refocusing service and research priorities in psychiatry toward problems of major mental illness and its long-term management requires that more specific attention be paid to this area by residency training programs. A \"community neuropsychiatry\" residency training experience based in a state hospital aftercare clinic is described as one model for achieving this objective. Supplemented by didactic course work in mental health administration, the history and theory of community psychiatry, and experiences in other, varied service settings, this program has proved to be valuable for learning and teaching skills basic to community psychiatry practice.", "contents": "The aftercare clinic as a residency training site. 'Community neuropsychiatry'. Refocusing service and research priorities in psychiatry toward problems of major mental illness and its long-term management requires that more specific attention be paid to this area by residency training programs. A \"community neuropsychiatry\" residency training experience based in a state hospital aftercare clinic is described as one model for achieving this objective. Supplemented by didactic course work in mental health administration, the history and theory of community psychiatry, and experiences in other, varied service settings, this program has proved to be valuable for learning and teaching skills basic to community psychiatry practice."}
{"id": "PMID:233713", "title": "[Dangerous side effects of lithium therapy].", "content": "A report is made on two cases of a pharmacogenic delirium as a result of combined lithium-haloperidol therapy, and on one case of lithium-induced diabetes insipidus renales with second-degree high pressure. Also, the development of a hydrocephalus internus male-resorptivus through lithium is discussed. In all patients there was a possible disposition due to old age or cerebral injury. Based on their effect on synaptic transmission the potentiating effect of lithium and haloperidol is discussed. Under the influence of Na-K stimulated ATPase and, thus, of active transport and adenylcyclase a basic mechanism of lithium therapy and its side-effects is seen.", "contents": "[Dangerous side effects of lithium therapy]. A report is made on two cases of a pharmacogenic delirium as a result of combined lithium-haloperidol therapy, and on one case of lithium-induced diabetes insipidus renales with second-degree high pressure. Also, the development of a hydrocephalus internus male-resorptivus through lithium is discussed. In all patients there was a possible disposition due to old age or cerebral injury. Based on their effect on synaptic transmission the potentiating effect of lithium and haloperidol is discussed. Under the influence of Na-K stimulated ATPase and, thus, of active transport and adenylcyclase a basic mechanism of lithium therapy and its side-effects is seen."}
{"id": "PMID:233714", "title": "[Islet cell adenoma with acute neuropsychiatric symptoms].", "content": "The author, by reference to observations made on two cases of islet cell adenoma with cerebral symptoms, describes the most important symptoms of this multifaceted disease picture. Diagnostic possibilities are discussed, and surgical treatment as the method of choice is pointed out.", "contents": "[Islet cell adenoma with acute neuropsychiatric symptoms]. The author, by reference to observations made on two cases of islet cell adenoma with cerebral symptoms, describes the most important symptoms of this multifaceted disease picture. Diagnostic possibilities are discussed, and surgical treatment as the method of choice is pointed out."}
{"id": "PMID:233715", "title": "[Pathomechanisms of myasthenic crisis states].", "content": "From the point of view of the kind of fate of those people ill with myasthenia the crisis itself can be regarded as the most dangerous and usually the most problematic phenomenon. To the crisis belong all those conditions characteristic of serious respiratory failure and those occurring either as a direct result of myasthenia or due to other causes associated with other illnesses. Clinically, there are three main kinds of crisis: myasthenic, cholinergic, and oscillatory/,brittle\". There is the possibility of 3 directions of study on the crisis: The careful analysis, coordination, and observation of the clinical picture, with precise notation of the course of the illness. Analysis of the neuro-muscular types of blockade which occur in myasthenia. Interpretation of changes such as resistance and intolerance observed during the process and which conform to the pathomechanism. The author deals with problems mentioned with regard to his casuistry of 300 people ill with myasthenia.", "contents": "[Pathomechanisms of myasthenic crisis states]. From the point of view of the kind of fate of those people ill with myasthenia the crisis itself can be regarded as the most dangerous and usually the most problematic phenomenon. To the crisis belong all those conditions characteristic of serious respiratory failure and those occurring either as a direct result of myasthenia or due to other causes associated with other illnesses. Clinically, there are three main kinds of crisis: myasthenic, cholinergic, and oscillatory/,brittle\". There is the possibility of 3 directions of study on the crisis: The careful analysis, coordination, and observation of the clinical picture, with precise notation of the course of the illness. Analysis of the neuro-muscular types of blockade which occur in myasthenia. Interpretation of changes such as resistance and intolerance observed during the process and which conform to the pathomechanism. The author deals with problems mentioned with regard to his casuistry of 300 people ill with myasthenia."}
{"id": "PMID:233716", "title": "[Studies of a full night's sleep in patients with absences].", "content": "Clinical electro-encephalography and especially the simultaneous recording of EEG values and other physiological parameters can greatly contribute to investigations into the neurophysiological aspects of sleep disturbances in patients suffering from attacks. In the case of absences peak potentials have been found in all phases of sleep, with a reduction in the pattern-like arrangement of the peak potentials and an increase in the irregular spike-and-wave complexes. During the dream phase, however, the peak potentials of these patients were primarily in the form of \"patterns\" comparable to the situation when they were awake. This evidence of epileptic activity throughout all sleep phases of patients suffering from absences makes it necessary to give anticonvulsive drugs in three doses distributed evenly over the entire day.", "contents": "[Studies of a full night's sleep in patients with absences]. Clinical electro-encephalography and especially the simultaneous recording of EEG values and other physiological parameters can greatly contribute to investigations into the neurophysiological aspects of sleep disturbances in patients suffering from attacks. In the case of absences peak potentials have been found in all phases of sleep, with a reduction in the pattern-like arrangement of the peak potentials and an increase in the irregular spike-and-wave complexes. During the dream phase, however, the peak potentials of these patients were primarily in the form of \"patterns\" comparable to the situation when they were awake. This evidence of epileptic activity throughout all sleep phases of patients suffering from absences makes it necessary to give anticonvulsive drugs in three doses distributed evenly over the entire day."}
{"id": "PMID:233718", "title": "Pyruvate kinase isozymes of Mucor racemosus: control of synthesis by glucose.", "content": "A variety of cultural conditions were examined to determine the relationship between pyruvate kinase isozyme patterns and morphology in Mucor racemosus. The results indicate that M. racemosus has two isozymes of pyruvate kinase, form A and form B, which are clearly separable on ion-exchange columns (diethylaminoethyl-cellulose). Addition of glucose to cultures growing on amino acids in air resulted in the induction of form A and the termination of form B synthesis. Cycloheximide added at the same time as glucose blocked the formation of form A but did not interfere with the termination of form B synthesis. Removal of glucose resulted in termination of form A synthesis and the induction of form B. Cycloheximide blocked the induction of form B and did not interfere with the termination of form A synthesis. The data show that the isozyme type is not directly related to morphology, but depends only on the presence or absence of glucose.", "contents": "Pyruvate kinase isozymes of Mucor racemosus: control of synthesis by glucose. A variety of cultural conditions were examined to determine the relationship between pyruvate kinase isozyme patterns and morphology in Mucor racemosus. The results indicate that M. racemosus has two isozymes of pyruvate kinase, form A and form B, which are clearly separable on ion-exchange columns (diethylaminoethyl-cellulose). Addition of glucose to cultures growing on amino acids in air resulted in the induction of form A and the termination of form B synthesis. Cycloheximide added at the same time as glucose blocked the formation of form A but did not interfere with the termination of form B synthesis. Removal of glucose resulted in termination of form A synthesis and the induction of form B. Cycloheximide blocked the induction of form B and did not interfere with the termination of form A synthesis. The data show that the isozyme type is not directly related to morphology, but depends only on the presence or absence of glucose."}
{"id": "PMID:233719", "title": "Functional stability of the bfe and tonB gene products in Escherichia coli.", "content": "The expression of several functional properties of the products of the bfe and tonB genes in Escherichia coli was measured after the specific termination of the synthesis of the products of these genes. This was accomplished by the use of a temperature-sensitive amber suppressor mutation, which allowed control, by manipulation of the growth temperature, of the level of product formed from suppressible mutant alleles of the bfe or tonB gene. The bfe product is an outer membrane receptor protein for vitamin B12, the E-colicins, and bacteriophage BF23. The identity of the tonB product is unknown, but it is necessary for a subsequent step of uptake of vitamin B12, iron chelates, all of the group B colicins, and bacteriophages T1 and phi 80. Results from a different experimental system had shown that the termination of expression of the bfe locus was rapidly followed by loss of sensitivity to colicins E2 and E3 and, subsequently, to bacteriophage BF23. This was confirmed with this experimental system. Receptors that were no longer functional for colicin or phage uptake remained fully effective for B12 uptake, showing that receptors are stable on the cell surface. This supports previous contentions for the presence of different functional states for colicin receptors. The functional properties of the tonB product, measured by B12 uptake or sensitivity to the group B colicin D, were unstable, declining extensively after cessation of its synthesis.", "contents": "Functional stability of the bfe and tonB gene products in Escherichia coli. The expression of several functional properties of the products of the bfe and tonB genes in Escherichia coli was measured after the specific termination of the synthesis of the products of these genes. This was accomplished by the use of a temperature-sensitive amber suppressor mutation, which allowed control, by manipulation of the growth temperature, of the level of product formed from suppressible mutant alleles of the bfe or tonB gene. The bfe product is an outer membrane receptor protein for vitamin B12, the E-colicins, and bacteriophage BF23. The identity of the tonB product is unknown, but it is necessary for a subsequent step of uptake of vitamin B12, iron chelates, all of the group B colicins, and bacteriophages T1 and phi 80. Results from a different experimental system had shown that the termination of expression of the bfe locus was rapidly followed by loss of sensitivity to colicins E2 and E3 and, subsequently, to bacteriophage BF23. This was confirmed with this experimental system. Receptors that were no longer functional for colicin or phage uptake remained fully effective for B12 uptake, showing that receptors are stable on the cell surface. This supports previous contentions for the presence of different functional states for colicin receptors. The functional properties of the tonB product, measured by B12 uptake or sensitivity to the group B colicin D, were unstable, declining extensively after cessation of its synthesis."}
{"id": "PMID:233720", "title": "Physiological function of superoxide dismutase in glucose-limited chemostat cultures of Escherichia coli.", "content": "Conditions for continuous culture of Escherichia coli K-12 His- Thi- under glucose limitation were established. Both the capacity for respiration, at D greater than 0.2/h, and specific activity of superoxide dismutase increased as a function of specific growth rate, whereas peroxidase and catalase were either invariant with or inversely related to this growth rate. The abrupt increase in the availability of glucose, as a means of elevating the growth rate, was followed by an increase in superoxide dismutase, which reached a plateau before there was a significant increase in the growth rate. Thus, an increase in superoxide dismutase appeared to be a prerequisite for an increase in the rate of growth. Cells that had higher levels of superoxide dismutase, because of varying specific growth rates, were more resistant to the toxicity of hyperbaric oxygen. Superoxide dismutase thus behaved like an essential defense against the toxicity of oxygen. Sensitivity towards streptonigrin increased with specific growth rate in the range of 0.09 to 0.25/h but decreased with further increases in the growth rate. Since this antibiotic has been shown to shunt electrons to oxygen, with concomitant production of O2-, these results indicated a progressive deficiency of reducing power at growth rates below 0.25/h and a surfeit of reducing power with progressively greater protection against O2- by superoxide dismutase at growth rates greater than 0.25/h.", "contents": "Physiological function of superoxide dismutase in glucose-limited chemostat cultures of Escherichia coli. Conditions for continuous culture of Escherichia coli K-12 His- Thi- under glucose limitation were established. Both the capacity for respiration, at D greater than 0.2/h, and specific activity of superoxide dismutase increased as a function of specific growth rate, whereas peroxidase and catalase were either invariant with or inversely related to this growth rate. The abrupt increase in the availability of glucose, as a means of elevating the growth rate, was followed by an increase in superoxide dismutase, which reached a plateau before there was a significant increase in the growth rate. Thus, an increase in superoxide dismutase appeared to be a prerequisite for an increase in the rate of growth. Cells that had higher levels of superoxide dismutase, because of varying specific growth rates, were more resistant to the toxicity of hyperbaric oxygen. Superoxide dismutase thus behaved like an essential defense against the toxicity of oxygen. Sensitivity towards streptonigrin increased with specific growth rate in the range of 0.09 to 0.25/h but decreased with further increases in the growth rate. Since this antibiotic has been shown to shunt electrons to oxygen, with concomitant production of O2-, these results indicated a progressive deficiency of reducing power at growth rates below 0.25/h and a surfeit of reducing power with progressively greater protection against O2- by superoxide dismutase at growth rates greater than 0.25/h."}
{"id": "PMID:233717", "title": "Rates of ion movement from plasma to endolymph in the dogfish.", "content": "The rates of movement of Na+, Rb+, Cl- and HCO3- from plasma to endolymph were studied in the elasmobranch fish, Squalus acanthias, by use of the appropriate isotopes. Rb+ was used as a marker for K+. The half-times to equilibrium for Na+, Rb+ and Cl- were about 100 hours; for HCO3- it was 6 hours. The equilibrium ratios, endolymph/plasma, are Na+ 0.87, K+ 26, Cl- 1.37, HCO3- 1.47. Carbonic anhydrase inhibition decreased the rate of HCO3- accumulation, suggesting that the process is actually the formation of endolymphatic HCO3- from plasma or tissue CO2. Increase in plasma pCO2 elevates endolymph HCO3- concentration. The secretory tissue contains carbonic anhydrase and Na-K-ATPase. These and other data suggest that a dominant feature of endolymph chemistry may be HCO3- formation linked in some fashion with K+ transport, through rates catalyzed by these two enzymes.", "contents": "Rates of ion movement from plasma to endolymph in the dogfish. The rates of movement of Na+, Rb+, Cl- and HCO3- from plasma to endolymph were studied in the elasmobranch fish, Squalus acanthias, by use of the appropriate isotopes. Rb+ was used as a marker for K+. The half-times to equilibrium for Na+, Rb+ and Cl- were about 100 hours; for HCO3- it was 6 hours. The equilibrium ratios, endolymph/plasma, are Na+ 0.87, K+ 26, Cl- 1.37, HCO3- 1.47. Carbonic anhydrase inhibition decreased the rate of HCO3- accumulation, suggesting that the process is actually the formation of endolymphatic HCO3- from plasma or tissue CO2. Increase in plasma pCO2 elevates endolymph HCO3- concentration. The secretory tissue contains carbonic anhydrase and Na-K-ATPase. These and other data suggest that a dominant feature of endolymph chemistry may be HCO3- formation linked in some fashion with K+ transport, through rates catalyzed by these two enzymes."}
{"id": "PMID:233721", "title": "Control of beta-glucosidase synthesis in Mucor racemosus.", "content": "The beta-glucosidase of Mucor racemosus was shown to be synthesized when the organism was grown in the presence of such diverse carbon sources as glycerol, lactate, xylose, ribose, alpha-methylglucoside, alpha-phenylglucoside, maltose, and cellobiose. Enzyme synthesis was strongly repressed in the presence of hexoses. In addition, exogenous cyclic adenosine 3',5'-monophosphate (cAMP) resulted in enzyme repression. When cAMP was added exogenously after enzyme activity had accumulated, a reversible enzyme inactivation occurred. Growth on disaccharides (maltose or cellobiose) was severely retarded in the presence of cAMP, whereas that on glucose remained unaffected. The results indicate a probable role for cAMP in control of glucosidase synthesis in Mucor.", "contents": "Control of beta-glucosidase synthesis in Mucor racemosus. The beta-glucosidase of Mucor racemosus was shown to be synthesized when the organism was grown in the presence of such diverse carbon sources as glycerol, lactate, xylose, ribose, alpha-methylglucoside, alpha-phenylglucoside, maltose, and cellobiose. Enzyme synthesis was strongly repressed in the presence of hexoses. In addition, exogenous cyclic adenosine 3',5'-monophosphate (cAMP) resulted in enzyme repression. When cAMP was added exogenously after enzyme activity had accumulated, a reversible enzyme inactivation occurred. Growth on disaccharides (maltose or cellobiose) was severely retarded in the presence of cAMP, whereas that on glucose remained unaffected. The results indicate a probable role for cAMP in control of glucosidase synthesis in Mucor."}
{"id": "PMID:233722", "title": "Glycine metabolism by Pseudomonas aeruginosa: hydrogen cyanide biosynthesis.", "content": "Hydrogen cyanide (HCN) production by Pseudomonas aeruginosa in a synthetic medium is stimulated by the presence of glycine. Methionine enhances this stimulation but will not substitute for glycine as a stimulator of cyanogenesis. Threonine and phenylalanine are effective substitutes for glycine in the stimulation of HCN production. Glycine, threonine, and serine are good radioisotope precursors of HCN, but methionine and phenylalanine are not. Cell extracts of P. aeruginosa convert [14C]threonine to [14C]glycine. H14CN is produced with low dilution of label from either [1-14C]glycine or [2-14C]glycine, indicating a randomization of label either in the primary or secondary metabolism of glycine. When whole cells were fed [1,2-14C]glycine, cyanide and bicarbonate were the only radioactive extracellular products observed.", "contents": "Glycine metabolism by Pseudomonas aeruginosa: hydrogen cyanide biosynthesis. Hydrogen cyanide (HCN) production by Pseudomonas aeruginosa in a synthetic medium is stimulated by the presence of glycine. Methionine enhances this stimulation but will not substitute for glycine as a stimulator of cyanogenesis. Threonine and phenylalanine are effective substitutes for glycine in the stimulation of HCN production. Glycine, threonine, and serine are good radioisotope precursors of HCN, but methionine and phenylalanine are not. Cell extracts of P. aeruginosa convert [14C]threonine to [14C]glycine. H14CN is produced with low dilution of label from either [1-14C]glycine or [2-14C]glycine, indicating a randomization of label either in the primary or secondary metabolism of glycine. When whole cells were fed [1,2-14C]glycine, cyanide and bicarbonate were the only radioactive extracellular products observed."}
{"id": "PMID:233723", "title": "Changes in protein synthesis on mitomycin C induction of wild-type and mutant CloDF13 plasmids.", "content": "Mitomycin C treatment of Escherichia coli K-12 cells containing the nonconjugative plasmid CloDF13 resulted in inhibition of host chromosome protein synthesis and a high rate of synthesis of two CloDF13-specified proteins whose molecular weights correspond to cloacin and immunity protein. Five molecules of immunity protein were synthesized for each cloacin DF13 molecule. Mitomycin C-treated cells containing a copy mutant of CloDF13 made three to four times as much of each protein as cells containing wild-type CloDF13. CloDF13 plasmids that contained the transposon Tn1 were isolated. Two did not induce after mitomycin C treatment, failing both to inhibit host cell synthesis and to produce the two new proteins. In minicells, they showed reduced CloDF13-specified protein synthesis and produced three Tn1-specified proteins.", "contents": "Changes in protein synthesis on mitomycin C induction of wild-type and mutant CloDF13 plasmids. Mitomycin C treatment of Escherichia coli K-12 cells containing the nonconjugative plasmid CloDF13 resulted in inhibition of host chromosome protein synthesis and a high rate of synthesis of two CloDF13-specified proteins whose molecular weights correspond to cloacin and immunity protein. Five molecules of immunity protein were synthesized for each cloacin DF13 molecule. Mitomycin C-treated cells containing a copy mutant of CloDF13 made three to four times as much of each protein as cells containing wild-type CloDF13. CloDF13 plasmids that contained the transposon Tn1 were isolated. Two did not induce after mitomycin C treatment, failing both to inhibit host cell synthesis and to produce the two new proteins. In minicells, they showed reduced CloDF13-specified protein synthesis and produced three Tn1-specified proteins."}
{"id": "PMID:233724", "title": "Analysis of Euglena gracilis chloroplast deoxyribonucleic acid with a restriction endonuclease, EcoRI.", "content": "Cleavage of chloroplast deoxyribonucleic acid (DNA) of Euglena gracilis Z with restriction endonuclease RI from Escherichia coli (EcoRI) yielded 23 bands upon electrophoresis in gels of agarose. Four of the bands contained twice the stoichiometric amount of DNA. One of these bands contained two similarly sized fragments. The sum of the molecular weight of the 24 different fragments equaled the molecular weight of the circular molecule. The restriction fragments had different buoyant densities, with four having distinctly heavy densities in CsCl. Restriction fragments with a high buoyant density were preferentially lost when broken chloroplast DNA was purified by equilibrium density gradient centrifugation. Hybridization of chloroplast ribosomal ribonucleic acid to intact chloroplast DNA determined that there are two cistrons for 16S and 23S ribosomal ribonucleic acid. These two cistrons are located on six restriction fragments, all of which have buoyant densities greater than the intact molecule of chloroplast DNA.", "contents": "Analysis of Euglena gracilis chloroplast deoxyribonucleic acid with a restriction endonuclease, EcoRI. Cleavage of chloroplast deoxyribonucleic acid (DNA) of Euglena gracilis Z with restriction endonuclease RI from Escherichia coli (EcoRI) yielded 23 bands upon electrophoresis in gels of agarose. Four of the bands contained twice the stoichiometric amount of DNA. One of these bands contained two similarly sized fragments. The sum of the molecular weight of the 24 different fragments equaled the molecular weight of the circular molecule. The restriction fragments had different buoyant densities, with four having distinctly heavy densities in CsCl. Restriction fragments with a high buoyant density were preferentially lost when broken chloroplast DNA was purified by equilibrium density gradient centrifugation. Hybridization of chloroplast ribosomal ribonucleic acid to intact chloroplast DNA determined that there are two cistrons for 16S and 23S ribosomal ribonucleic acid. These two cistrons are located on six restriction fragments, all of which have buoyant densities greater than the intact molecule of chloroplast DNA."}
{"id": "PMID:233725", "title": "Characterization of lambda Escherichia coli hybrids carrying chemotaxis genes.", "content": "Molecular cloning techniques were used to construct hybrid Escherichia coli lambda phage and isolate Col E1 factors that carried the cheB region of the E. coli genome. The products of these genes were examined by using a series of deletions in the phage to stimulate specific polypeptide synthesis in ultraviolet-irradiated cells and by using Col factor to program protein synthesis in minicells. Seven flagellar related polypeptides were synthesized. Three of these with apparent molecular weights of 38,000, 28,000, and 8,000 were associated with the cheB region; three polypeptides 63,000, 61,000, and 60,000 were associated with the region that maps between cheB and cheA. These bands were referred to as the triplet group. We suggest that these polypeptides are the same as the methyl-accepting chemotaxis protein described by Kort et al. (Proc. Natl. Acad. Sci. U.S.A. 72:3939-3943, 1975). Another polypeptide with a molecular weight of 12,000 is associated with the cheA region which also produces at least three gene products. We conclude that the cheA-cheB region in E. coli is complex. Further genetic and biochemical analyses are required to describe all of these products.", "contents": "Characterization of lambda Escherichia coli hybrids carrying chemotaxis genes. Molecular cloning techniques were used to construct hybrid Escherichia coli lambda phage and isolate Col E1 factors that carried the cheB region of the E. coli genome. The products of these genes were examined by using a series of deletions in the phage to stimulate specific polypeptide synthesis in ultraviolet-irradiated cells and by using Col factor to program protein synthesis in minicells. Seven flagellar related polypeptides were synthesized. Three of these with apparent molecular weights of 38,000, 28,000, and 8,000 were associated with the cheB region; three polypeptides 63,000, 61,000, and 60,000 were associated with the region that maps between cheB and cheA. These bands were referred to as the triplet group. We suggest that these polypeptides are the same as the methyl-accepting chemotaxis protein described by Kort et al. (Proc. Natl. Acad. Sci. U.S.A. 72:3939-3943, 1975). Another polypeptide with a molecular weight of 12,000 is associated with the cheA region which also produces at least three gene products. We conclude that the cheA-cheB region in E. coli is complex. Further genetic and biochemical analyses are required to describe all of these products."}
{"id": "PMID:233726", "title": "Selected translocation of plasmid genes: frequency and regional specificity of translocation of the Tn3 element.", "content": "A procedure is described that selects for the insertion of transposable antibiotic resistance elements in a variety of recipient replicons. The selected translocation procedure, which employs a plasmid having a temperature-sensitive defect in replication as a donor of transposable genetic elements, was used to investigate certain characteristics of the translocation process. Our results indicate that translocation of the Tn3 element from plasmid to plasmid occurs at a 10(3)- to 10(4)-times-higher frequency than from plasmid to chromosome. In both cases, continued accumulation of Tn3 on recipient genomes is prevented by development of an apparent equilibrium when only a small fraction of molecules in the recipient population contain Tn3. An alternative method for estimation of translocation frequency has shown that the translocation process is temperature sensitive and that its frequency is unaffected by the presence of host recA mutation. Insertions of Tn3 onto the 65 X 10(6)-dalton R6-5 plasmid in Escherichia coli are clustered on EcoRI fragments 3 (8 of 23 insertions) and 9 (7 of 23 insertions), which contain 12 and 5%, respectively, of the R6-5 genome. The occurrence of multiple insertions of Tn3 within EcoRI fragment 9, which contains the IS1 element and a terminus of the Tn4 element, is consistent with earlier evidence indicating that terminal deoxyribonucleic acid sequences of already present transposable elements may provide recognition sequences for subsequent illegitimate recombinational events.", "contents": "Selected translocation of plasmid genes: frequency and regional specificity of translocation of the Tn3 element. A procedure is described that selects for the insertion of transposable antibiotic resistance elements in a variety of recipient replicons. The selected translocation procedure, which employs a plasmid having a temperature-sensitive defect in replication as a donor of transposable genetic elements, was used to investigate certain characteristics of the translocation process. Our results indicate that translocation of the Tn3 element from plasmid to plasmid occurs at a 10(3)- to 10(4)-times-higher frequency than from plasmid to chromosome. In both cases, continued accumulation of Tn3 on recipient genomes is prevented by development of an apparent equilibrium when only a small fraction of molecules in the recipient population contain Tn3. An alternative method for estimation of translocation frequency has shown that the translocation process is temperature sensitive and that its frequency is unaffected by the presence of host recA mutation. Insertions of Tn3 onto the 65 X 10(6)-dalton R6-5 plasmid in Escherichia coli are clustered on EcoRI fragments 3 (8 of 23 insertions) and 9 (7 of 23 insertions), which contain 12 and 5%, respectively, of the R6-5 genome. The occurrence of multiple insertions of Tn3 within EcoRI fragment 9, which contains the IS1 element and a terminus of the Tn4 element, is consistent with earlier evidence indicating that terminal deoxyribonucleic acid sequences of already present transposable elements may provide recognition sequences for subsequent illegitimate recombinational events."}
{"id": "PMID:233727", "title": "Dominance of dnaA+ to dnaA in Escherichia coli.", "content": "The dominance of dnaA+ to the dnaA508 mutation was complete and was unaffected by the presence of a copy of the chromosomal replication origin on the episome. These results prove that the dnaA gene of Escherichia coli produces a diffusible product.", "contents": "Dominance of dnaA+ to dnaA in Escherichia coli. The dominance of dnaA+ to the dnaA508 mutation was complete and was unaffected by the presence of a copy of the chromosomal replication origin on the episome. These results prove that the dnaA gene of Escherichia coli produces a diffusible product."}
{"id": "PMID:233728", "title": "Pelvic osteomyelitis in children.", "content": "Six children (7 to 16 years of age) with pelvic osteomyelitis are described. Sites of involvement included the pubis in three patients, the ilium in two patients, and the ischium in one patient. All were right-sided. Each patient presented with a history of fever and an abnormal gait. In four, the point tenderness indicated the site of bony involvement. All patients had pain on abduction but free passive range of motion of the hip. Soft tissue swelling was present on admission pelvic roentgenograms in five patients. Intravenous pyelogram revealed deviation of the bladder toward the midline in each of four patients studied. Roentgenographic changes typical of osteomyelitis developed in four patients ten days to ten weeks after onset of symptoms. In four patients in whom an organism was identified, Staphylococcus aureus was isolated from blood and/or bone. All isolates were methicillin-sensitive and two were penicillin-sensitive. Purulent material was drained from three of the five patients who underwent surgical exploration of the pelvis. All patients received parenteral antistaphylococcal therapy for 3 to 5 1/2 weeks (mean, 4 weeks). Oral antibiotics were given to five patients for an additional 3 to 14 weeks. All patients recovered completely.", "contents": "Pelvic osteomyelitis in children. Six children (7 to 16 years of age) with pelvic osteomyelitis are described. Sites of involvement included the pubis in three patients, the ilium in two patients, and the ischium in one patient. All were right-sided. Each patient presented with a history of fever and an abnormal gait. In four, the point tenderness indicated the site of bony involvement. All patients had pain on abduction but free passive range of motion of the hip. Soft tissue swelling was present on admission pelvic roentgenograms in five patients. Intravenous pyelogram revealed deviation of the bladder toward the midline in each of four patients studied. Roentgenographic changes typical of osteomyelitis developed in four patients ten days to ten weeks after onset of symptoms. In four patients in whom an organism was identified, Staphylococcus aureus was isolated from blood and/or bone. All isolates were methicillin-sensitive and two were penicillin-sensitive. Purulent material was drained from three of the five patients who underwent surgical exploration of the pelvis. All patients received parenteral antistaphylococcal therapy for 3 to 5 1/2 weeks (mean, 4 weeks). Oral antibiotics were given to five patients for an additional 3 to 14 weeks. All patients recovered completely."}
{"id": "PMID:233729", "title": "Antimicrobial activity of metronidazole in anaerobic bacteria.", "content": "The antimicrobial activity of metronidazole was investigated in anaerobic bacteria by use of time-viability studies. This antimicrobial agent has a rapid onset of bactericidal activity under proper reducing conditions. The bactericidal rates were not affected by inoculum size or nutritional requirements, nor by inhibition of growth and protein synthesis by chloramphenicol. Using supernatant fractions of actively growing cultures of susceptible organisms, we observed a disappearance of metronidazole and a loss of biological activity, but there was no significant change in preparations from resistant bacteria. The decrease in drug concentration with susceptible cells occurred during the time that its bactericidal action was being exerted. Extracts from susceptible organisms rapidly reduced the concentration of metronidazole, confirming previous observations which suggest that the drug acts as a terminal electron acceptor. Radioisotope experiments with [14C]metronidazole revealed that the compound was taken up by both resistant and susceptible bacteria, although there was a difference in rate and extent of accumulation. These studies demonstrate that metronidazole's antimicrobial activity against anaerobic bacteria is bactericidal and independent of growth rate, and that it involves the uptake and metabolism of the compound.", "contents": "Antimicrobial activity of metronidazole in anaerobic bacteria. The antimicrobial activity of metronidazole was investigated in anaerobic bacteria by use of time-viability studies. This antimicrobial agent has a rapid onset of bactericidal activity under proper reducing conditions. The bactericidal rates were not affected by inoculum size or nutritional requirements, nor by inhibition of growth and protein synthesis by chloramphenicol. Using supernatant fractions of actively growing cultures of susceptible organisms, we observed a disappearance of metronidazole and a loss of biological activity, but there was no significant change in preparations from resistant bacteria. The decrease in drug concentration with susceptible cells occurred during the time that its bactericidal action was being exerted. Extracts from susceptible organisms rapidly reduced the concentration of metronidazole, confirming previous observations which suggest that the drug acts as a terminal electron acceptor. Radioisotope experiments with [14C]metronidazole revealed that the compound was taken up by both resistant and susceptible bacteria, although there was a difference in rate and extent of accumulation. These studies demonstrate that metronidazole's antimicrobial activity against anaerobic bacteria is bactericidal and independent of growth rate, and that it involves the uptake and metabolism of the compound."}
{"id": "PMID:233730", "title": "5-Propyl-2'-deoxyuridine: a specific anti-herpes agent.", "content": "In both primary rabbit kidney cells and human skin fibroblasts, 5-propyl-2'-deoxyuridine proved inhibitory to herpes simplex virus at a concentration as low as 1 micrograms/ml, whereas concentrations higher than 200 micrograms/ml were required to inhibit vaccinia virus replication or normal cell metabolism.", "contents": "5-Propyl-2'-deoxyuridine: a specific anti-herpes agent. In both primary rabbit kidney cells and human skin fibroblasts, 5-propyl-2'-deoxyuridine proved inhibitory to herpes simplex virus at a concentration as low as 1 micrograms/ml, whereas concentrations higher than 200 micrograms/ml were required to inhibit vaccinia virus replication or normal cell metabolism."}
{"id": "PMID:233733", "title": "Sensory conduction studies in the early recognition of nerve disorders.", "content": "Early investigations into sensory conduction are reviewed and related to recent and ongoing research, specifically with relation to the early detection of nerve disorders. Current study on entrapment neuropathies and on the assessment of minor sensory conduction changes is presented. It is concluded that, in the early recognition of nerve disease, the clinical orientation of the electromyographer is essential to proper test interpretation.", "contents": "Sensory conduction studies in the early recognition of nerve disorders. Early investigations into sensory conduction are reviewed and related to recent and ongoing research, specifically with relation to the early detection of nerve disorders. Current study on entrapment neuropathies and on the assessment of minor sensory conduction changes is presented. It is concluded that, in the early recognition of nerve disease, the clinical orientation of the electromyographer is essential to proper test interpretation."}
{"id": "PMID:233734", "title": "Early recognition of nerve disorders by near-nerve recording of sensory action potentials.", "content": "Evaluated herein are the advantages and limitations of recording sensory action potentials with a gross electrode placed near the nerve. This technique has proved to be a sensitive measure of early nerve damage for two reasons: first, electrodes can be positioned in such a way that maximal velocity is determined only along the abnormal stretch of the nerve; and second, small late components originating from demyelinated, remyelinated, or regenerating fibers can be detected.", "contents": "Early recognition of nerve disorders by near-nerve recording of sensory action potentials. Evaluated herein are the advantages and limitations of recording sensory action potentials with a gross electrode placed near the nerve. This technique has proved to be a sensitive measure of early nerve damage for two reasons: first, electrodes can be positioned in such a way that maximal velocity is determined only along the abnormal stretch of the nerve; and second, small late components originating from demyelinated, remyelinated, or regenerating fibers can be detected."}
{"id": "PMID:233735", "title": "Histology and ultrastructure of alterations in neuropathy.", "content": "Histologic findings are described in nerves from men exposed to lead, from patients with discrete clinical signs of peripheral neuropathy, and from controls. Every nerve from control subjects showed an abnormality (paranodal remyelination, segmental remyelination, or regeneration) in teased fibers. The only histologic alteration in eight lead-exposed males without signs or symptoms of neuropathy was a slightly increased incidence of paranodal remyelination. Sixteen patients with discrete neurologic symptoms and signs had a loss of large myelinated fibers and an increased incidence of regenerated fibers among teased fibers. Electron microscopy of unmyelinated fibers showed an increased occurrence of Schwann-cell processes, of fibers undergoing degeneration, and of Schwann-cell subunits with many profiles as the earliest signs of abnormality. Clinically mild neuropathies may exhibit advanced regeneration in the case of unmyelinated fibers. The earliest sign of degeneration in myelinated fibers was a diminution in the number of axonal organelles.", "contents": "Histology and ultrastructure of alterations in neuropathy. Histologic findings are described in nerves from men exposed to lead, from patients with discrete clinical signs of peripheral neuropathy, and from controls. Every nerve from control subjects showed an abnormality (paranodal remyelination, segmental remyelination, or regeneration) in teased fibers. The only histologic alteration in eight lead-exposed males without signs or symptoms of neuropathy was a slightly increased incidence of paranodal remyelination. Sixteen patients with discrete neurologic symptoms and signs had a loss of large myelinated fibers and an increased incidence of regenerated fibers among teased fibers. Electron microscopy of unmyelinated fibers showed an increased occurrence of Schwann-cell processes, of fibers undergoing degeneration, and of Schwann-cell subunits with many profiles as the earliest signs of abnormality. Clinically mild neuropathies may exhibit advanced regeneration in the case of unmyelinated fibers. The earliest sign of degeneration in myelinated fibers was a diminution in the number of axonal organelles."}
{"id": "PMID:233736", "title": "Recognition of unmyelinated fiber disease: morphologic criteria.", "content": "An attempt is made to evaluate available information regarding the integrity of unmyelinated fibers, particularly somatic unmyelinated fibers in man and in other primates, with relation to early recognition of nerve disorders. Discussion is limited to morphologic aspects of these fibers.", "contents": "Recognition of unmyelinated fiber disease: morphologic criteria. An attempt is made to evaluate available information regarding the integrity of unmyelinated fibers, particularly somatic unmyelinated fibers in man and in other primates, with relation to early recognition of nerve disorders. Discussion is limited to morphologic aspects of these fibers."}
{"id": "PMID:233737", "title": "Neurophysiological investigation of subclinical and minimal toxic neuropathies.", "content": "In the investigation of subclinical or minimal toxic neuropathies, selection of the proper electrophysiological test depends largely on the nature of the condition being studied. Examples are given of several toxic disorders, and their features are discussed in relation to the appropriate electrophysiological measurement.", "contents": "Neurophysiological investigation of subclinical and minimal toxic neuropathies. In the investigation of subclinical or minimal toxic neuropathies, selection of the proper electrophysiological test depends largely on the nature of the condition being studied. Examples are given of several toxic disorders, and their features are discussed in relation to the appropriate electrophysiological measurement."}
{"id": "PMID:233738", "title": "Screening for peripheral neuropathy in patients treated by chronic hemodialysis.", "content": "Observations were made on the occurrence of peripheral neuropathy in a series of 139 patients admitted to a chronic dialysis program over a 10-year period. Evidence of neuropathy was obtained in approximately 50% of these patients over the total period. Once dialysis was instituted, distal paresthesiae evident before the inception of dialysis tended to clear rapidly. Occurrence of the symptom of \"restless legs\" correlated positively with the presence of neuropathy. Persistent neuropathy was more commonly sensory than motor, and its features were consistent with a predominant loss of large myelinated fibers. This analysis suggests that multiple factors may be involved in the origin of uremic neuropathy.", "contents": "Screening for peripheral neuropathy in patients treated by chronic hemodialysis. Observations were made on the occurrence of peripheral neuropathy in a series of 139 patients admitted to a chronic dialysis program over a 10-year period. Evidence of neuropathy was obtained in approximately 50% of these patients over the total period. Once dialysis was instituted, distal paresthesiae evident before the inception of dialysis tended to clear rapidly. Occurrence of the symptom of \"restless legs\" correlated positively with the presence of neuropathy. Persistent neuropathy was more commonly sensory than motor, and its features were consistent with a predominant loss of large myelinated fibers. This analysis suggests that multiple factors may be involved in the origin of uremic neuropathy."}
{"id": "PMID:233741", "title": "Magnetic resonance studies of Mn(II)-, Mn(III)-, and Fe(III)-conalbumin complexes.", "content": "Apoconalbumin binds Mn(II) at two sites with association constants of K1 = 7 (+/- 1) X 10(4) and K2 = 0.4 (+/- 0.25) X 10(4) M-1. The binding is tighter in the presence of excess bicarbonate resulting in K1 = 1.8 (+/- 0.2) X 10(5) and K2 = 3 (+/- 2) X 10(4) M-1. The electron paramagnetic resonance spectrum (at both 9 and 35 GHz) of Mn(II) bound at the tight site reveals a rhombic distortion (lambda = E/D approximately equal to 0.25-0.31) in the protein ligand environment of the mental ion. An evaluation of the 1/pT1p, paramagnetic contribution to the longitudinal relaxation rate of solvent protons with Mn(II)-, Mn(III)-, and Fe(III)-derivatives of conalbumin revealed that the mental ion in each site of conalbumin is accessible to one water molecule. For Mn(II)-conalbumin and Mn(III)-conalbumin species, inner coordination sphere protons are rapidly exchanging with the bulk solvent, while slow exchange conditions prevail for Fe(III)-conalbumin.", "contents": "Magnetic resonance studies of Mn(II)-, Mn(III)-, and Fe(III)-conalbumin complexes. Apoconalbumin binds Mn(II) at two sites with association constants of K1 = 7 (+/- 1) X 10(4) and K2 = 0.4 (+/- 0.25) X 10(4) M-1. The binding is tighter in the presence of excess bicarbonate resulting in K1 = 1.8 (+/- 0.2) X 10(5) and K2 = 3 (+/- 2) X 10(4) M-1. The electron paramagnetic resonance spectrum (at both 9 and 35 GHz) of Mn(II) bound at the tight site reveals a rhombic distortion (lambda = E/D approximately equal to 0.25-0.31) in the protein ligand environment of the mental ion. An evaluation of the 1/pT1p, paramagnetic contribution to the longitudinal relaxation rate of solvent protons with Mn(II)-, Mn(III)-, and Fe(III)-derivatives of conalbumin revealed that the mental ion in each site of conalbumin is accessible to one water molecule. For Mn(II)-conalbumin and Mn(III)-conalbumin species, inner coordination sphere protons are rapidly exchanging with the bulk solvent, while slow exchange conditions prevail for Fe(III)-conalbumin."}
{"id": "PMID:233739", "title": "The effect of anticholinesterases on motor unit potentials in myasthenia gravis.", "content": "In most patients with myasthenia gravis, the mean duration and amplitude of motor unit potentials sampled in the extensor digitorum communis muscle, as well as the amplitude of the pattern of activity during full effort, increased after application of anticholinesterase. This appears to be a sensitive test for early detection of failure in neuromuscular transmission. In a series of 12 patients, the mean amplitude of motor unit potentials increased 30%-130% in 9, and the mean duration increased 10%-25% in 7. In 3 patients who failed to show an increase in amplitude in the extensor digitorum communis muscle, the amplitude of motor unit potentials increased in a facial or extraocular muscle after intravenous application of edrophonium. This increase in the amplitude or duration of motor unit potentials was even evident in 4 patients who failed to show a decrement in response of the opponens pollicis muscle to repetitive stimuli delivered to the median nerve at 3/sec and 5/sec. In 5 patients, responses evoked by stimuli delivered at 15/sec showed marked facilitation.", "contents": "The effect of anticholinesterases on motor unit potentials in myasthenia gravis. In most patients with myasthenia gravis, the mean duration and amplitude of motor unit potentials sampled in the extensor digitorum communis muscle, as well as the amplitude of the pattern of activity during full effort, increased after application of anticholinesterase. This appears to be a sensitive test for early detection of failure in neuromuscular transmission. In a series of 12 patients, the mean amplitude of motor unit potentials increased 30%-130% in 9, and the mean duration increased 10%-25% in 7. In 3 patients who failed to show an increase in amplitude in the extensor digitorum communis muscle, the amplitude of motor unit potentials increased in a facial or extraocular muscle after intravenous application of edrophonium. This increase in the amplitude or duration of motor unit potentials was even evident in 4 patients who failed to show a decrement in response of the opponens pollicis muscle to repetitive stimuli delivered to the median nerve at 3/sec and 5/sec. In 5 patients, responses evoked by stimuli delivered at 15/sec showed marked facilitation."}
{"id": "PMID:233742", "title": "Secretory endometrium associated with breakthrough bleeding in estrogen-treated postmenopausal women.", "content": "Paradoxical secretory changes are described in benign endometria curetted for breakthrough bleeding in postmenopausal women on cyclic low dosage Premarin therapy. This purely histologic study, though favoring progesterone mediation, provides no definitive answer to the problem of pathogenesis. Future correlative morphologic and endocrine investigations are clearly indicated.", "contents": "Secretory endometrium associated with breakthrough bleeding in estrogen-treated postmenopausal women. Paradoxical secretory changes are described in benign endometria curetted for breakthrough bleeding in postmenopausal women on cyclic low dosage Premarin therapy. This purely histologic study, though favoring progesterone mediation, provides no definitive answer to the problem of pathogenesis. Future correlative morphologic and endocrine investigations are clearly indicated."}
{"id": "PMID:233743", "title": "Incidental pregnancy luteoma associated with ectopic tubo-ovarian pregnancy: evidence in favor of origin from theca interna of an atretic follicle.", "content": "An incidental pregnancy luteoma was identified microscopically in an ovary submitted for ruptured ectopic tubo-ovarian pregnancy. The lesion consisted of a localized, non-encapsulated proliferation of thecal cells in the wall of an atretic follicle and had all the pathologic features of the typical late pregnancy luteoma. This finding is presented to support the origin of the pregnancy luteoma from the theca interna of atretic follicles.", "contents": "Incidental pregnancy luteoma associated with ectopic tubo-ovarian pregnancy: evidence in favor of origin from theca interna of an atretic follicle. An incidental pregnancy luteoma was identified microscopically in an ovary submitted for ruptured ectopic tubo-ovarian pregnancy. The lesion consisted of a localized, non-encapsulated proliferation of thecal cells in the wall of an atretic follicle and had all the pathologic features of the typical late pregnancy luteoma. This finding is presented to support the origin of the pregnancy luteoma from the theca interna of atretic follicles."}
{"id": "PMID:233744", "title": "Immunoprophylactic anti-Rho(D) treatment after mismatched transfusions.", "content": "80 cases of anti-Rho(D) treatment after mismatched transfusions are reviewed to compare the intramuscular (i.m.) and intravenous (i.v.) route of treatment. No severe reactions such as renal failure occurred with either method of anti-D treatment. If the Rh-immune globulin is injected i.m., 20 micrograms anti-D per ml red cells are used. For i.v. anti-D administration, 10-12 micrograms anti-D are suggested. The i.v. method of anti-D treatment is recommended for the future. Furthermore, a scheme of treatment for after mismatched transfusions is described.", "contents": "Immunoprophylactic anti-Rho(D) treatment after mismatched transfusions. 80 cases of anti-Rho(D) treatment after mismatched transfusions are reviewed to compare the intramuscular (i.m.) and intravenous (i.v.) route of treatment. No severe reactions such as renal failure occurred with either method of anti-D treatment. If the Rh-immune globulin is injected i.m., 20 micrograms anti-D per ml red cells are used. For i.v. anti-D administration, 10-12 micrograms anti-D are suggested. The i.v. method of anti-D treatment is recommended for the future. Furthermore, a scheme of treatment for after mismatched transfusions is described."}
{"id": "PMID:233746", "title": "Diffusion rates of cell surface antigens of mouse-human heterokaryons. I. Analysis of the population.", "content": "The rate of appearance, in a newly formed heterokaryon population, of cells bearing completely intermixed mouse and human surface antigens may be used to estimate diffusion constants for antigens on individual cells. From this estimate, it appears that the surface antigens in most cells do not diffuse at the rate expected, but rather move more slowly, by a factor of ten or more, than expected from either measured or calculated diffusion constants for proteins freely mobile in the plane of a lipid membrane. Differences in diffusion rates between cells are not due to effects of Sendai virus, or of trypsin. Restrictions on diffusion are apparently not due to cytochalasin B- or Colcemid-sensitive elements.", "contents": "Diffusion rates of cell surface antigens of mouse-human heterokaryons. I. Analysis of the population. The rate of appearance, in a newly formed heterokaryon population, of cells bearing completely intermixed mouse and human surface antigens may be used to estimate diffusion constants for antigens on individual cells. From this estimate, it appears that the surface antigens in most cells do not diffuse at the rate expected, but rather move more slowly, by a factor of ten or more, than expected from either measured or calculated diffusion constants for proteins freely mobile in the plane of a lipid membrane. Differences in diffusion rates between cells are not due to effects of Sendai virus, or of trypsin. Restrictions on diffusion are apparently not due to cytochalasin B- or Colcemid-sensitive elements."}
{"id": "PMID:233747", "title": "Topographical localization of the receptors for luteinizing hormone-releasing hormone on the surface of dissociated pituitary cells.", "content": "A derivative of the hypothalamic peptide luteinizing hormone-releasing hormone (LHRH) has been coupled to ferritin and the conjugate purified by gel chromatography. In its ability to stimulate the secretion of luteinizing hormone from pituitary cells in vitro, the conjugate has the same potency and specificity as the native peptide. When dissociated pituitary cells maintained in short-term culture are lightly fixed with formaldehyde and then incubated with the conjugate, examination in the electron microscope shows an even distribution of ferritin particles over the free cell surface of the gonadotrophin cells. This binding appears to be specific for the LHRH receptor since it is prevented by a 10-fold excess of native peptide. In addition to the gonadotrophin cells, some somatotrophin and thyrotrophin cells bind conjugate on their free surfaces under similar conditions. If living cells are incubated with the conjugate for 15 min, the bound conjugate becomes aggregated and then concentrated in one localized area of the cell surface. In this area, which lies immediately above the juxtanuclear Golgi complex, the plasma membrane is frequently invaginated in a manner which suggests that the bound, aggregated conjugate is internalized by endocytosis.", "contents": "Topographical localization of the receptors for luteinizing hormone-releasing hormone on the surface of dissociated pituitary cells. A derivative of the hypothalamic peptide luteinizing hormone-releasing hormone (LHRH) has been coupled to ferritin and the conjugate purified by gel chromatography. In its ability to stimulate the secretion of luteinizing hormone from pituitary cells in vitro, the conjugate has the same potency and specificity as the native peptide. When dissociated pituitary cells maintained in short-term culture are lightly fixed with formaldehyde and then incubated with the conjugate, examination in the electron microscope shows an even distribution of ferritin particles over the free cell surface of the gonadotrophin cells. This binding appears to be specific for the LHRH receptor since it is prevented by a 10-fold excess of native peptide. In addition to the gonadotrophin cells, some somatotrophin and thyrotrophin cells bind conjugate on their free surfaces under similar conditions. If living cells are incubated with the conjugate for 15 min, the bound conjugate becomes aggregated and then concentrated in one localized area of the cell surface. In this area, which lies immediately above the juxtanuclear Golgi complex, the plasma membrane is frequently invaginated in a manner which suggests that the bound, aggregated conjugate is internalized by endocytosis."}
{"id": "PMID:233745", "title": "Juvenile nasopharyngeal angiofibroma: management of intracranial extension.", "content": "Juvenile nasopharyngeal angiofibroma (JNA) is a histologically benign, locally invasive tumor of the nasopharynx that is found primarily in the pubescent male. While most authors recommend surgical excision for smaller, localized extracranial tumors, opinion varies on the management of more aggressive tumors with intracranial extension. The authors present their experience over the past 15 years with 15 cases of JNA with intracranial extension, and formulate a plan of management. A combined otolaryngologic/neurosurgical approach is recommended in order to assess the extent of the tumor and to isolate feeding vessels. Lateral extension into the middle cranial fossae should be resected in continuity with the nasopharyngeal component, which is approached from below in a separate operative field. Medial extensions are transected, verified angiographically three months after surgery, and irradiated. The results of therapy are presented, and a case of dural penetration by JNA is described.", "contents": "Juvenile nasopharyngeal angiofibroma: management of intracranial extension. Juvenile nasopharyngeal angiofibroma (JNA) is a histologically benign, locally invasive tumor of the nasopharynx that is found primarily in the pubescent male. While most authors recommend surgical excision for smaller, localized extracranial tumors, opinion varies on the management of more aggressive tumors with intracranial extension. The authors present their experience over the past 15 years with 15 cases of JNA with intracranial extension, and formulate a plan of management. A combined otolaryngologic/neurosurgical approach is recommended in order to assess the extent of the tumor and to isolate feeding vessels. Lateral extension into the middle cranial fossae should be resected in continuity with the nasopharyngeal component, which is approached from below in a separate operative field. Medial extensions are transected, verified angiographically three months after surgery, and irradiated. The results of therapy are presented, and a case of dural penetration by JNA is described."}
{"id": "PMID:233748", "title": "Is there a role for actin in virus budding?", "content": "Electrophoretic data from both sodium dodecyl sulfate-polyacrylamide gels (SDS-PAGE) and acid-urea gels reveal a protein in purified murine mammary tumor virus (MuMTV) which co-migrates with purified chick skeletal muscle actin. 125I-labeling of intact and disrupted virus preparations shows that the actin-like protein is not artifactually adsorbed to the outside of virions during isolation. Quantitative SDS-PAGE and examination of negatively stained preparations show that the actin cannot be accounted for by a contaminating population of virus-free vesicles. The ultrastructure of mammary epithelial cells and of Rous sarcoma virus-transformed chick embryo fibroblasts shows that virus extrusion is associated with filament-containing cellular processes. In particular, MuMTV is released from the ends of long microvilli which contain a bundle of 6-8-nm microfilaments and share other structural features with intestinal microvilli. We suggest that virus nucleoids require an interaction with host cell contractile proteins for their extrusion from the cell.", "contents": "Is there a role for actin in virus budding? Electrophoretic data from both sodium dodecyl sulfate-polyacrylamide gels (SDS-PAGE) and acid-urea gels reveal a protein in purified murine mammary tumor virus (MuMTV) which co-migrates with purified chick skeletal muscle actin. 125I-labeling of intact and disrupted virus preparations shows that the actin-like protein is not artifactually adsorbed to the outside of virions during isolation. Quantitative SDS-PAGE and examination of negatively stained preparations show that the actin cannot be accounted for by a contaminating population of virus-free vesicles. The ultrastructure of mammary epithelial cells and of Rous sarcoma virus-transformed chick embryo fibroblasts shows that virus extrusion is associated with filament-containing cellular processes. In particular, MuMTV is released from the ends of long microvilli which contain a bundle of 6-8-nm microfilaments and share other structural features with intestinal microvilli. We suggest that virus nucleoids require an interaction with host cell contractile proteins for their extrusion from the cell."}
{"id": "PMID:233750", "title": "Glomus tumour of the fingers.", "content": "Clinical and therapeutic aspects of glomus tumour of the fingers have been considered by analyzing the records of 15 patients with glomus tumours. The tumour was found in the pulp in 5 patients and in the subungual region in 10. The diagnosis may be difficult to make and patients are often believed to be malingering. Complete surgical excision under magnification is curative.", "contents": "Glomus tumour of the fingers. Clinical and therapeutic aspects of glomus tumour of the fingers have been considered by analyzing the records of 15 patients with glomus tumours. The tumour was found in the pulp in 5 patients and in the subungual region in 10. The diagnosis may be difficult to make and patients are often believed to be malingering. Complete surgical excision under magnification is curative."}
{"id": "PMID:233754", "title": "Labile (borderline) hypertension--new aspects of a common disorder.", "content": "Labile hypertension in patients under 50 years of age (the non-atherosclerotic form) was found to be characterized by higher urinary excretion of catecholamines and particularly of homovanillic acid; when further analyzed it was shown to be a heterogeneous entity with two types of patients clinically and biochemically distinguishable from each other, from control subjects and from patients with stable hypertension. Reactivity to assuming an upright posture distinguishes one type of labile hypertension having a normal postural pulse rate response from another having an excessive postural increase in pulse rate. The first group also showed normal responses of plasma norepinephrine concentration and of urinary cyclic AMP to posture. The group with excessive pulse rate response, in contrast, showed a decrease in plasma norepinephrine and an excessive increase of urinary cyclic AMP excretion in response to upright posture. The results suggest that not only circulating catecholamines but also the reactivity of their target tissues (as probably reflected by cyclic AMP measurements) are important in bringing about signs of adrenergic excess. The hypothesis that cyclic AMP changes reflect beta-adrenergic receptor reactivity is strongly favoured by data indicating qualitative differences in cyclic AMP responses to beta-adrenergic stimulation or inhibition between control subjects and those labile hypertensive patients with clinical signs of excessive sympathetic reactivity. The study stresses the need for more precise definition of labile hypertension, for dynamic clinical and biochemical correlative studies, and for consideration not only of the circulating hormones but also of the \"second messengers\" (such as cyclic AMP and cyclic GMP) which reflect the cellular action of hormones. Blood pressure is a very labile parameter in health and disease. In one sense, therefore, hypertension can be considered \"labile\" in every hypertensive patient. Usually, however, labile (or borderline) hypertension is regarded as characterized by a blood pressure over 140/90 mmHg, falling below these values with physical and emotional rest. This clinical entity, which affects some 20% (variously estimated between 16 and 30%) of the adult population, gives rise to uncertainties in both definition and prognosis. In some patients labile hypertension represents the precursor of a fixed hypertensive state, whereas in many others it remains labile throughout life, never progressing to the stable phase nor becoming associated with hypertensive cardiovascular disease.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Labile (borderline) hypertension--new aspects of a common disorder. Labile hypertension in patients under 50 years of age (the non-atherosclerotic form) was found to be characterized by higher urinary excretion of catecholamines and particularly of homovanillic acid; when further analyzed it was shown to be a heterogeneous entity with two types of patients clinically and biochemically distinguishable from each other, from control subjects and from patients with stable hypertension. Reactivity to assuming an upright posture distinguishes one type of labile hypertension having a normal postural pulse rate response from another having an excessive postural increase in pulse rate. The first group also showed normal responses of plasma norepinephrine concentration and of urinary cyclic AMP to posture. The group with excessive pulse rate response, in contrast, showed a decrease in plasma norepinephrine and an excessive increase of urinary cyclic AMP excretion in response to upright posture. The results suggest that not only circulating catecholamines but also the reactivity of their target tissues (as probably reflected by cyclic AMP measurements) are important in bringing about signs of adrenergic excess. The hypothesis that cyclic AMP changes reflect beta-adrenergic receptor reactivity is strongly favoured by data indicating qualitative differences in cyclic AMP responses to beta-adrenergic stimulation or inhibition between control subjects and those labile hypertensive patients with clinical signs of excessive sympathetic reactivity. The study stresses the need for more precise definition of labile hypertension, for dynamic clinical and biochemical correlative studies, and for consideration not only of the circulating hormones but also of the \"second messengers\" (such as cyclic AMP and cyclic GMP) which reflect the cellular action of hormones. Blood pressure is a very labile parameter in health and disease. In one sense, therefore, hypertension can be considered \"labile\" in every hypertensive patient. Usually, however, labile (or borderline) hypertension is regarded as characterized by a blood pressure over 140/90 mmHg, falling below these values with physical and emotional rest. This clinical entity, which affects some 20% (variously estimated between 16 and 30%) of the adult population, gives rise to uncertainties in both definition and prognosis. In some patients labile hypertension represents the precursor of a fixed hypertensive state, whereas in many others it remains labile throughout life, never progressing to the stable phase nor becoming associated with hypertensive cardiovascular disease.(ABSTRACT TRUNCATED AT 400 WORDS)"}
{"id": "PMID:233757", "title": "Fibrillar bodies in leukemic cells revealed by polarization microscopy.", "content": "An optical polarizing microscope with a good coefficient of extinction permits the visualization of the cytoplasmic fibrillar body in living preparations and smears of leukemic cells (human leukemias and the L 5222 experimental leukemia). These inclusions are not visible by phase contrast microscopy nor in fixed and stained smears. The detection in living cells of fibrillar bodies makes it possible to study directly the conditions for their formation and their reaction to the effect of certain drugs.", "contents": "Fibrillar bodies in leukemic cells revealed by polarization microscopy. An optical polarizing microscope with a good coefficient of extinction permits the visualization of the cytoplasmic fibrillar body in living preparations and smears of leukemic cells (human leukemias and the L 5222 experimental leukemia). These inclusions are not visible by phase contrast microscopy nor in fixed and stained smears. The detection in living cells of fibrillar bodies makes it possible to study directly the conditions for their formation and their reaction to the effect of certain drugs."}
{"id": "PMID:233758", "title": "[Role of thermography in the diagnosis of breast neoplasms].", "content": "319 cases of breast pathology of doubtful clinical diagnosis were studied by means of thermography and mammography, with histological verification: 214 proved to be malignant tumours and 105 benign. The role of thermography is discussed on the basis of these results; it would appear to be restricted to diagnostic aid status associated with other procedures, particularly clinical examination and mammography.", "contents": "[Role of thermography in the diagnosis of breast neoplasms]. 319 cases of breast pathology of doubtful clinical diagnosis were studied by means of thermography and mammography, with histological verification: 214 proved to be malignant tumours and 105 benign. The role of thermography is discussed on the basis of these results; it would appear to be restricted to diagnostic aid status associated with other procedures, particularly clinical examination and mammography."}
{"id": "PMID:233759", "title": "[Intestinal transit time in Togo (Western Africa) and Germany].", "content": "In five groups of Africans and Europeans in Togo (West-Africa) and Germany intestinal transit time and stool-weights have been studied. Native Africans on traditional food passed three times more stool (307 g/d) in half of the time (33 hours) as Europeans and Africans on Western diet did. The effect of dietary fibre on intestinal transit time and intestinal pathology is stressed.", "contents": "[Intestinal transit time in Togo (Western Africa) and Germany]. In five groups of Africans and Europeans in Togo (West-Africa) and Germany intestinal transit time and stool-weights have been studied. Native Africans on traditional food passed three times more stool (307 g/d) in half of the time (33 hours) as Europeans and Africans on Western diet did. The effect of dietary fibre on intestinal transit time and intestinal pathology is stressed."}
{"id": "PMID:233760", "title": "Screening for neurobehavioral toxicity: the need for and examples of validation of testing procedures.", "content": "The need for a sensitive and reliable screen to assess environmental agents for potential behavioral and neurological toxicity is discussed. Factors involving strategy, choice of animals and doses, route of administration, duration of study and requirements for the selection of neurobehavioral tests are also evaluated. The primary emphasis concerns the need for standardization and validation of neurobehavioral tests to be used in neurotoxicology. It is suggested that test validation be accomplished by comparing the observed results of known neurotoxicants in animal models which are chosen to predict effects based on reported human symptomatology. As a means of demonstrating how test validation is used in our laboratory, data from a number of experiments concerning the effects of a variety of chemical agents on three measures of motor functioning were discussed. The neurobehavioral effects of acrylamide, and agent known to produce \"dying-back\" axonopathies, were assessed using separate techniques presumed to measure hindlimb and forelimb functioning and general motor activity. The prediction that acrylamide will first decrease hindlimb functioning, while decreasing forelimb grip strength and motor activity at higher doses, was confirmed. The validity of the hindlimb measurement was supported using a neurotoxicant, carbon disulfide, known to affect motor functioning in a manner similar to acrylamide. The validity of the forelimb technique was shown indirectly using normative data collected from rats of both sexes tested at various ages, i.e., males were stronger than females and grip scores changed as a function of age. The relative sensitivities of the fore- and hindlimb measurements were found to be approximately the same when used to assess the effects of known muscle relaxants, such as phenobarbital and chlordiazepoxide. Finally, it was predicted and confirmed that an environmental agent believed to affect behavior secondarily to effects on other organ systems would affect all measures of motor functioning at approximately the same dose.", "contents": "Screening for neurobehavioral toxicity: the need for and examples of validation of testing procedures. The need for a sensitive and reliable screen to assess environmental agents for potential behavioral and neurological toxicity is discussed. Factors involving strategy, choice of animals and doses, route of administration, duration of study and requirements for the selection of neurobehavioral tests are also evaluated. The primary emphasis concerns the need for standardization and validation of neurobehavioral tests to be used in neurotoxicology. It is suggested that test validation be accomplished by comparing the observed results of known neurotoxicants in animal models which are chosen to predict effects based on reported human symptomatology. As a means of demonstrating how test validation is used in our laboratory, data from a number of experiments concerning the effects of a variety of chemical agents on three measures of motor functioning were discussed. The neurobehavioral effects of acrylamide, and agent known to produce \"dying-back\" axonopathies, were assessed using separate techniques presumed to measure hindlimb and forelimb functioning and general motor activity. The prediction that acrylamide will first decrease hindlimb functioning, while decreasing forelimb grip strength and motor activity at higher doses, was confirmed. The validity of the hindlimb measurement was supported using a neurotoxicant, carbon disulfide, known to affect motor functioning in a manner similar to acrylamide. The validity of the forelimb technique was shown indirectly using normative data collected from rats of both sexes tested at various ages, i.e., males were stronger than females and grip scores changed as a function of age. The relative sensitivities of the fore- and hindlimb measurements were found to be approximately the same when used to assess the effects of known muscle relaxants, such as phenobarbital and chlordiazepoxide. Finally, it was predicted and confirmed that an environmental agent believed to affect behavior secondarily to effects on other organ systems would affect all measures of motor functioning at approximately the same dose."}
{"id": "PMID:233761", "title": "Use of discrimination behavior for the evaluation of toxicants.", "content": "This study involved the application of discrimination behavior for the study of effects of environmental contaminants on the behavior of laboratory animals. Polybrominated biphenyl (PBB) was evaluated for effects on the acquisition and performance of a simple auditory discrimination by rats. Methyl ethyl ketone (MEK), methyl isobutyl ketone (MIBK) and carbon monoxide (CO) were evaluated for effects on a delayed match-to-sample discrimination task in the juvenile baboon. All of the contaminants slowed response times and increased extra responses. These findings suggest that discrimination behavior may be of value for the evaluation of environmental contaminants for effects on the central nervous system.", "contents": "Use of discrimination behavior for the evaluation of toxicants. This study involved the application of discrimination behavior for the study of effects of environmental contaminants on the behavior of laboratory animals. Polybrominated biphenyl (PBB) was evaluated for effects on the acquisition and performance of a simple auditory discrimination by rats. Methyl ethyl ketone (MEK), methyl isobutyl ketone (MIBK) and carbon monoxide (CO) were evaluated for effects on a delayed match-to-sample discrimination task in the juvenile baboon. All of the contaminants slowed response times and increased extra responses. These findings suggest that discrimination behavior may be of value for the evaluation of environmental contaminants for effects on the central nervous system."}
{"id": "PMID:233764", "title": "Insoluble \"fibrin\" in human aortic intima. Quantitative studies on the relationship between insoluble \"fibrin\", soluble fibrinogen and low density lipoprotein.", "content": "A quantitative assay for fibrin or other insoluble fibrin-like antigens (\"fibrin\") in small samples of intima is described. Tissue samples were subjected to electrophoresis directly from the intima into an antibody-containing gel to remove and measure fibrinogen and other soluble fibrin reactive antigens (FRA). The residual tissue was then exhaustively incubated with plasmin, and the soluble fragments generated from the insoluble \"fibrin\" were measured by quantitative immunoelectrophoresis. \"Fibrin\" accounted for about 2% of the tissue dry weight in normal intima and the ratio fibrinogen/\"fibrin\" was 1-1.5. In the gelatinous lesions, which seem to be the precursors of fibrous plaques, there was a small increase in \"fibrin\" but a substantial increase in fibrinogen and low density (LD)-lipoprotein, and the ratio fibrinogen/\"fibrin\" rose to about 3, which suggests that the increase in \"fibrin\" is secondary to increased permeation of fibrinogen. At the edges of large plaques there was also a threefold increase in fibrinogen, but \"fibrin\" increased fivefold, and accounted for 10% of the tissue dry weight. The same high concentration was found in the centres of large fibrous plaques with advanced atheroma lipid. Raised levels of \"fibrin\" were accompanied by raised levels of fibrinogen in most tissue samples. About 80% of the total soluble FRA could be clotted with thrombin; there was no significant difference between normal intima and lesions, and the proportion clotted was not related to \"fibrin\" content.", "contents": "Insoluble \"fibrin\" in human aortic intima. Quantitative studies on the relationship between insoluble \"fibrin\", soluble fibrinogen and low density lipoprotein. A quantitative assay for fibrin or other insoluble fibrin-like antigens (\"fibrin\") in small samples of intima is described. Tissue samples were subjected to electrophoresis directly from the intima into an antibody-containing gel to remove and measure fibrinogen and other soluble fibrin reactive antigens (FRA). The residual tissue was then exhaustively incubated with plasmin, and the soluble fragments generated from the insoluble \"fibrin\" were measured by quantitative immunoelectrophoresis. \"Fibrin\" accounted for about 2% of the tissue dry weight in normal intima and the ratio fibrinogen/\"fibrin\" was 1-1.5. In the gelatinous lesions, which seem to be the precursors of fibrous plaques, there was a small increase in \"fibrin\" but a substantial increase in fibrinogen and low density (LD)-lipoprotein, and the ratio fibrinogen/\"fibrin\" rose to about 3, which suggests that the increase in \"fibrin\" is secondary to increased permeation of fibrinogen. At the edges of large plaques there was also a threefold increase in fibrinogen, but \"fibrin\" increased fivefold, and accounted for 10% of the tissue dry weight. The same high concentration was found in the centres of large fibrous plaques with advanced atheroma lipid. Raised levels of \"fibrin\" were accompanied by raised levels of fibrinogen in most tissue samples. About 80% of the total soluble FRA could be clotted with thrombin; there was no significant difference between normal intima and lesions, and the proportion clotted was not related to \"fibrin\" content."}
{"id": "PMID:233767", "title": "Participation of calcium in flagellar shortening and regeneration in Chlamydomonas reinhardii.", "content": "Cation chelators cause flagellar shortening in Chlamydomonas reinhardii. Most effective are EDTA and EGTA (1 mM) but pyrophosphate (10 mM) also is effective. Addition of 5 mM Ca2+ after shortening caused by 4 mM EGTA results in flagellar regeneration. Other divalent cations can replace Ca2+ with the following relative activities: Ca2+ greater than Sr2+ = Mn2+ much greater than Ba2+ = Mg2+. Although the specific ion requirement to reverse shortening is not clear, it is possible that all of the ions act by displacing one bound cation, presumably Ca2+. A specific requirement for Ca2+ in flagellar regeneration could be demonstrated, however, because as little as 50 microM EGTA in the presence of 500 microM Mg2+ delayed regeneration and prevented full regeneration. Ca2+ at 100 microM overcame this inhibition.", "contents": "Participation of calcium in flagellar shortening and regeneration in Chlamydomonas reinhardii. Cation chelators cause flagellar shortening in Chlamydomonas reinhardii. Most effective are EDTA and EGTA (1 mM) but pyrophosphate (10 mM) also is effective. Addition of 5 mM Ca2+ after shortening caused by 4 mM EGTA results in flagellar regeneration. Other divalent cations can replace Ca2+ with the following relative activities: Ca2+ greater than Sr2+ = Mn2+ much greater than Ba2+ = Mg2+. Although the specific ion requirement to reverse shortening is not clear, it is possible that all of the ions act by displacing one bound cation, presumably Ca2+. A specific requirement for Ca2+ in flagellar regeneration could be demonstrated, however, because as little as 50 microM EGTA in the presence of 500 microM Mg2+ delayed regeneration and prevented full regeneration. Ca2+ at 100 microM overcame this inhibition."}
{"id": "PMID:233765", "title": "Very low density lipoproteins in normal and cholesterol-fed rabbits: lipid and protein composition and metabolism. Part 1. Chemical composition of very low density lipoproteins in rabbits.", "content": "The lipid and apoprotein composition of very low density lipoproteins (VLDL) (d less than 1.019 g/ml) from normal and hypercholesteremic (h.c.) rabbits are compared. Significant changes are observed in the apoproteins, as well as in the fatty acid composition of cholesterol esters, and in the relative distribution of phospholipids. Apoproteins show a marked increase of peptides with slow mobility (R2 and R3), corresponding to arginine-rich proteins, both in the rabbit and in some types of human hyperlipoproteinemias (hypothyroidism and Fredrickson Type III). VLDL were separated into the two fractions, VLDL-1 and VLDL-2. Peptides of slow mobility were shown to be present in a higher concentration in VLDL-1. Cholesterol esters of h.c. VLDL have a very high content of oleic acid, the 18:1/18:2 ratio being about three times higher than in normal VLDL. Phospholipid distribution in h.c. VLDL is characterized by an increase of sphingomyelin and decrease of phosphatidylethanolamine. The PC/Sph ratio is about one fifth that of normal. These changes in VLDL lipids are very similar to those occurring in the lipid composition of the atherosclerotic plaques in mammals.", "contents": "Very low density lipoproteins in normal and cholesterol-fed rabbits: lipid and protein composition and metabolism. Part 1. Chemical composition of very low density lipoproteins in rabbits. The lipid and apoprotein composition of very low density lipoproteins (VLDL) (d less than 1.019 g/ml) from normal and hypercholesteremic (h.c.) rabbits are compared. Significant changes are observed in the apoproteins, as well as in the fatty acid composition of cholesterol esters, and in the relative distribution of phospholipids. Apoproteins show a marked increase of peptides with slow mobility (R2 and R3), corresponding to arginine-rich proteins, both in the rabbit and in some types of human hyperlipoproteinemias (hypothyroidism and Fredrickson Type III). VLDL were separated into the two fractions, VLDL-1 and VLDL-2. Peptides of slow mobility were shown to be present in a higher concentration in VLDL-1. Cholesterol esters of h.c. VLDL have a very high content of oleic acid, the 18:1/18:2 ratio being about three times higher than in normal VLDL. Phospholipid distribution in h.c. VLDL is characterized by an increase of sphingomyelin and decrease of phosphatidylethanolamine. The PC/Sph ratio is about one fifth that of normal. These changes in VLDL lipids are very similar to those occurring in the lipid composition of the atherosclerotic plaques in mammals."}
{"id": "PMID:233768", "title": "Cellular recognition by rat liver cells of neuraminidase-treated erythrocytes. Demonstration and analysis of cell contacts.", "content": "Freshly isolated rat liver cells adhere firmly to neuraminidase-treated rat or mouse erythrocytes but not to untreated erythrocytes. Binding between cells occurs only in the presence of calcium and is specially inhibited by D-galactose. We therefore suggest that cell adherence is mediated by a galactose-specific hepatic membrane receptor. Ultrastructural analysis of contact regions revealed point-like interactions between hepatic microvilli and erythrocytes and no broad areas of membrane contact. When liver cells are cultivated in vitro they lose their ability to bind erythrocytes within 24 h.", "contents": "Cellular recognition by rat liver cells of neuraminidase-treated erythrocytes. Demonstration and analysis of cell contacts. Freshly isolated rat liver cells adhere firmly to neuraminidase-treated rat or mouse erythrocytes but not to untreated erythrocytes. Binding between cells occurs only in the presence of calcium and is specially inhibited by D-galactose. We therefore suggest that cell adherence is mediated by a galactose-specific hepatic membrane receptor. Ultrastructural analysis of contact regions revealed point-like interactions between hepatic microvilli and erythrocytes and no broad areas of membrane contact. When liver cells are cultivated in vitro they lose their ability to bind erythrocytes within 24 h."}
{"id": "PMID:233766", "title": "Very low density lipoproteins in normal and cholesterol-fed rabbits: lipid and protein composition and metabolism. Part 2. Metabolism of very low density lipoproteins in rabbits.", "content": "The metabolic fate of very low density lipoproteins (VLDL) in normal and hypercholesteremic (h.c.) rabbits has been investigated. VLDL were labelled with 125I in the protein moieties and injected into normal and h.c. animals. The turnover of h.c. VLDL is markedly delayed as compared to that of normal VLDL, and conversion into lipoprotein classes of higher density is considerably decreased. This is observed when h.c. VLDL are injected either into h.c., or into normal rabbits. Arterial uptake of radioactivity is much higher with h.c. VLDL than with the normal lipoproteins, and it is highest when h.c. VLDL are injected into normal recipients. These data, together with those reported in the previous study, support the hypothesis that h.c. VLDL have an inherent atherogenicity. Injection of h.c. VLDL into normal animals also offers an experimental model for testing drugs or diets against atherosclerosis, using untreated animals.", "contents": "Very low density lipoproteins in normal and cholesterol-fed rabbits: lipid and protein composition and metabolism. Part 2. Metabolism of very low density lipoproteins in rabbits. The metabolic fate of very low density lipoproteins (VLDL) in normal and hypercholesteremic (h.c.) rabbits has been investigated. VLDL were labelled with 125I in the protein moieties and injected into normal and h.c. animals. The turnover of h.c. VLDL is markedly delayed as compared to that of normal VLDL, and conversion into lipoprotein classes of higher density is considerably decreased. This is observed when h.c. VLDL are injected either into h.c., or into normal rabbits. Arterial uptake of radioactivity is much higher with h.c. VLDL than with the normal lipoproteins, and it is highest when h.c. VLDL are injected into normal recipients. These data, together with those reported in the previous study, support the hypothesis that h.c. VLDL have an inherent atherogenicity. Injection of h.c. VLDL into normal animals also offers an experimental model for testing drugs or diets against atherosclerosis, using untreated animals."}
{"id": "PMID:233769", "title": "Nuclear control of neurite induction in neuroblastoma cells.", "content": "Induction of neurite formation in neuroblastoma cells by dibutyryl cyclic 3':5'-AMP (db-cAMP) or prostaglandin EI (PGE1) was enhanced after enucleation. Cells selected for resistance to db-cAMP were induced to form neurites by db-cAMP or PGE1 only after, but not before enucleation. Inhibition of protein synthesis inhibited neurite induction in nucleated, but not in enucleated cells, and enucleated cells were less sensitive to inhibition of neurite formation by concanavalin A (ConA). Colchicine, vinblastine and cytochalasin B (CB), compounds that interfere with the assembly of microtubules and microfilaments, inhibited induction in both types of cells. It is suggested that enucleation removes a nuclear inhibitor of neurite induction by db-cAMP and PGE1, and that neurite induction in nucleated cells requires that cAMP activates the assembly of microtubules and microfilaments and inactivates the nuclear inhibitor.", "contents": "Nuclear control of neurite induction in neuroblastoma cells. Induction of neurite formation in neuroblastoma cells by dibutyryl cyclic 3':5'-AMP (db-cAMP) or prostaglandin EI (PGE1) was enhanced after enucleation. Cells selected for resistance to db-cAMP were induced to form neurites by db-cAMP or PGE1 only after, but not before enucleation. Inhibition of protein synthesis inhibited neurite induction in nucleated, but not in enucleated cells, and enucleated cells were less sensitive to inhibition of neurite formation by concanavalin A (ConA). Colchicine, vinblastine and cytochalasin B (CB), compounds that interfere with the assembly of microtubules and microfilaments, inhibited induction in both types of cells. It is suggested that enucleation removes a nuclear inhibitor of neurite induction by db-cAMP and PGE1, and that neurite induction in nucleated cells requires that cAMP activates the assembly of microtubules and microfilaments and inactivates the nuclear inhibitor."}
{"id": "PMID:233770", "title": "Aggregation of sponge cells. XIV. Possible substitution of calcium ions by polycations.", "content": "Single cells from the siliceous sponge Geodia cydonium, obtained after chemical dissociation, reaggregate in the presence of the aggregation factor in Ca2+-containing medium to large aggregates. It was found that polyvalent organic cations (polylysine, spermine, spermidine, putrescine) enhance the Ca2+-mediated cell aggregation. In Ca2+-free medium these compounds also cause reaggregation; aggregates of a diameter up to 800 micron are formed within 120 min. Proteins, containing basic groups of amino acid residues have no influence on cell aggregation. Monovalent cations inhibit the reaggregation process. The enhancing effect of polyvalent organic cations on cell aggregation is dependent on the presence of the soluble aggregation factor. From the findings that polycations do not alter the duration of the lag phase (a characteristic of the aggregation factor-mediated Geodia cell reaggregation) and act in cooperation with the aggregation receptor, we assume that the polycations bind between the aggregation factor and the aggregation receptor.", "contents": "Aggregation of sponge cells. XIV. Possible substitution of calcium ions by polycations. Single cells from the siliceous sponge Geodia cydonium, obtained after chemical dissociation, reaggregate in the presence of the aggregation factor in Ca2+-containing medium to large aggregates. It was found that polyvalent organic cations (polylysine, spermine, spermidine, putrescine) enhance the Ca2+-mediated cell aggregation. In Ca2+-free medium these compounds also cause reaggregation; aggregates of a diameter up to 800 micron are formed within 120 min. Proteins, containing basic groups of amino acid residues have no influence on cell aggregation. Monovalent cations inhibit the reaggregation process. The enhancing effect of polyvalent organic cations on cell aggregation is dependent on the presence of the soluble aggregation factor. From the findings that polycations do not alter the duration of the lag phase (a characteristic of the aggregation factor-mediated Geodia cell reaggregation) and act in cooperation with the aggregation receptor, we assume that the polycations bind between the aggregation factor and the aggregation receptor."}
{"id": "PMID:233771", "title": "Sister chromatid exchange in patients with viral disease.", "content": "Sister chromatid exchange (SCE) frequencies were studied in differentially stained chromosomes from lymphocytes of 17 patients with viral disease. The mean SCE score for the patients was 8.7 +/- 2.9 standard deviations. SCE scores were significantly elevated in the patients compared with the controls (p less than 0.01); however, variability in SCE means was observed in the patients. SCE elevations were also present in long term cultured Epstein Barr virus positive human B lymphocytes.", "contents": "Sister chromatid exchange in patients with viral disease. Sister chromatid exchange (SCE) frequencies were studied in differentially stained chromosomes from lymphocytes of 17 patients with viral disease. The mean SCE score for the patients was 8.7 +/- 2.9 standard deviations. SCE scores were significantly elevated in the patients compared with the controls (p less than 0.01); however, variability in SCE means was observed in the patients. SCE elevations were also present in long term cultured Epstein Barr virus positive human B lymphocytes."}
{"id": "PMID:233774", "title": "Tissue metabolism and enzyme activities in the rodent Heterocephalus glaber, a poor temperature regulator.", "content": "1. Tissue oxygen uptake and enzyme activities were investigated in the naked mole rat, Heterocephalus glaber, a mammal notable for its low body temperature and metabolism and poor temperature regulating ability. 2. Q10 for O2 uptake of Heterocephalus crude liver homogenates ranged from 1.91 for the temperature interval 25-30 degrees C to 1.76 within the range 30-38 degrees C, values similar to those reported for typical homoiotherms. 3. Km pyruvate of lactate dehydrogenase in heart muscle had the same temperature dependence in the mole rat and mouse. 4. O2 uptake and cytochrome oxidase activity of skeletal muscle were higher for mole rat than mouse. The reverse was true for heart muscle. Brain and liver O2 uptake showed similar values for both species, while kidney O2 uptake was highest in the mouse. 5. Pyruvate kinase activity in heart and skeletal muscle was higher in mouse than mole rat, suggesting a greater reliance on glycolysis in the former. 6. Na+, K+ -ATPase activity of liver and kidney was 60% higher in mouse than mole rat, while brain was 30% higher in mouse. 7. The results indicate that the effects of temperature on tissue metabolism in the mole rat conform to those in typical homoiotherms. The low body temperature and O2 uptake in the mole rat find no expression in the tissue respiratory capacity.", "contents": "Tissue metabolism and enzyme activities in the rodent Heterocephalus glaber, a poor temperature regulator. 1. Tissue oxygen uptake and enzyme activities were investigated in the naked mole rat, Heterocephalus glaber, a mammal notable for its low body temperature and metabolism and poor temperature regulating ability. 2. Q10 for O2 uptake of Heterocephalus crude liver homogenates ranged from 1.91 for the temperature interval 25-30 degrees C to 1.76 within the range 30-38 degrees C, values similar to those reported for typical homoiotherms. 3. Km pyruvate of lactate dehydrogenase in heart muscle had the same temperature dependence in the mole rat and mouse. 4. O2 uptake and cytochrome oxidase activity of skeletal muscle were higher for mole rat than mouse. The reverse was true for heart muscle. Brain and liver O2 uptake showed similar values for both species, while kidney O2 uptake was highest in the mouse. 5. Pyruvate kinase activity in heart and skeletal muscle was higher in mouse than mole rat, suggesting a greater reliance on glycolysis in the former. 6. Na+, K+ -ATPase activity of liver and kidney was 60% higher in mouse than mole rat, while brain was 30% higher in mouse. 7. The results indicate that the effects of temperature on tissue metabolism in the mole rat conform to those in typical homoiotherms. The low body temperature and O2 uptake in the mole rat find no expression in the tissue respiratory capacity."}
{"id": "PMID:233775", "title": "The perchlorosoluble proteins of the serum of the rainbow trout (Salmo gairdnerii Richardson): albumin like and hemoglobin binding fraction.", "content": "1. The main perchlorosoluble fraction of rainbow trout serum has some physico-chemical characters kindred to those of human serum albumin (low molecular weight, solubility with ammonium sulfate, electrophoretic mobility, no glycoproteinic staining). 2. However, on account of obvious differences (heterogeneity and existence of various phenotypes, lack of bromophenol blue or bilirubin binding, low concentration, solubility in perchloric acid), the term \"para-albumin\" seems more suitable to name this compound. 3. The perchlorosoluble fraction binds hemoglobin causing an increase of peroxidasic activity. But, unlike to human haptoglobin, hemoglobin binding is partial, reversible and labile.", "contents": "The perchlorosoluble proteins of the serum of the rainbow trout (Salmo gairdnerii Richardson): albumin like and hemoglobin binding fraction. 1. The main perchlorosoluble fraction of rainbow trout serum has some physico-chemical characters kindred to those of human serum albumin (low molecular weight, solubility with ammonium sulfate, electrophoretic mobility, no glycoproteinic staining). 2. However, on account of obvious differences (heterogeneity and existence of various phenotypes, lack of bromophenol blue or bilirubin binding, low concentration, solubility in perchloric acid), the term \"para-albumin\" seems more suitable to name this compound. 3. The perchlorosoluble fraction binds hemoglobin causing an increase of peroxidasic activity. But, unlike to human haptoglobin, hemoglobin binding is partial, reversible and labile."}
{"id": "PMID:233772", "title": "Cyclic nucleotides in nervous tissue.", "content": "A review of the literature emphasizes that cyclic nucleotides play a key role in regulation of cell growth, differentiation and metabolism in diverse tissues and, in addition, are closely involved in neural tissue function. The role of cAMP as a second messenger is discussed.", "contents": "Cyclic nucleotides in nervous tissue. A review of the literature emphasizes that cyclic nucleotides play a key role in regulation of cell growth, differentiation and metabolism in diverse tissues and, in addition, are closely involved in neural tissue function. The role of cAMP as a second messenger is discussed."}
{"id": "PMID:233776", "title": "Variations in (Na+ + K+)-ATPase and Mg2+-ATPase activity of the ground squirrel brain during hibernation.", "content": "1. The specific activity of brain (Na+ + K+)-ATPase and Mg2+ -ATPase of the ground squirrel (Spermophilus richardsonii) is significantly increased after long-term hibernation. 2. The markedly non-linear thermal dependence of (Na+ + K+)-ATPase is unchanged during hibernation whereas the near linear thermal dependence of Mg2+-ATPase undergoes minor alteration after prolonged hibernation. 3. The sensitivity of (Na+ + K+)-ATPase to inhibition by ouabain is significantly decreased after 100 days of hibernation as is both the rate and amount of [3H]-ouabain binding. 4. These changes may be related to alteration in the phospholipid matrix of the membrane rather than alteration in the protein structure of the enzyme.", "contents": "Variations in (Na+ + K+)-ATPase and Mg2+-ATPase activity of the ground squirrel brain during hibernation. 1. The specific activity of brain (Na+ + K+)-ATPase and Mg2+ -ATPase of the ground squirrel (Spermophilus richardsonii) is significantly increased after long-term hibernation. 2. The markedly non-linear thermal dependence of (Na+ + K+)-ATPase is unchanged during hibernation whereas the near linear thermal dependence of Mg2+-ATPase undergoes minor alteration after prolonged hibernation. 3. The sensitivity of (Na+ + K+)-ATPase to inhibition by ouabain is significantly decreased after 100 days of hibernation as is both the rate and amount of [3H]-ouabain binding. 4. These changes may be related to alteration in the phospholipid matrix of the membrane rather than alteration in the protein structure of the enzyme."}
{"id": "PMID:233777", "title": "Serum lipoproteins in the spiny lobster, Panulirus interruptus.", "content": "1. Most of the lipids in the hemolymph of the spiny lobster, Panulirus interruptus, were associated with a high density lipoprotein (HDL3). The lipid of this lipoprotein was composed of phospholipid (88%), sterol (4%) and triglyceride (3%). 2. In animals fed 14C-labeled triglyceride radioactivity was not seen in the serum until 12 hr after feeding. Most of this serum radioactivity was associated with phosphatidyl choline. 3. Electron micrographs showed that negatively stained high density lipoproteins of the lobster had a polymorphic appearance.", "contents": "Serum lipoproteins in the spiny lobster, Panulirus interruptus. 1. Most of the lipids in the hemolymph of the spiny lobster, Panulirus interruptus, were associated with a high density lipoprotein (HDL3). The lipid of this lipoprotein was composed of phospholipid (88%), sterol (4%) and triglyceride (3%). 2. In animals fed 14C-labeled triglyceride radioactivity was not seen in the serum until 12 hr after feeding. Most of this serum radioactivity was associated with phosphatidyl choline. 3. Electron micrographs showed that negatively stained high density lipoproteins of the lobster had a polymorphic appearance."}
{"id": "PMID:233773", "title": "Protein phosphorylation in human synaptosomal membranes: evidence for the presence of substrates for cyclic nucleotide guanosine 3'-5'-monophosphate dependent protein kinases.", "content": "Synaptosomal membranes prepared from different anatomical regions of postmortem human brain readily incorporate phosphate when incubated with labelled ATP in vitro. Separation of proteins on SDS slab gels indicated up to 30 protein bands stained by Coomassie blue of which ten incorporated label, as detected by radioautography (mol. wt. range 16-110 K with a major double band at 49-50 K). Incorporation into the 110 K region appeared to increase in older persons, and that into the 49-50 K region decreased. Human but not rat membranes subjected to similar conditions of treatment failed to respond to the addition of cAMP at 10(-5) - 10(-7) M but were highly sensitive to the addition of cGMP at 10(-6) M, which led to intensification of existing bands and the appearance of a major band at 60 K. The 110 K band present in high concentration in white matter striatum, caudate nucleus, and putamen was insensitive to cGMP addition. The presence of cGMP-dependent protein kinase substrates has not previously been reported in synapses, and it may be of significance in view of the known sensitivity of this system to biological regulatory agents.", "contents": "Protein phosphorylation in human synaptosomal membranes: evidence for the presence of substrates for cyclic nucleotide guanosine 3'-5'-monophosphate dependent protein kinases. Synaptosomal membranes prepared from different anatomical regions of postmortem human brain readily incorporate phosphate when incubated with labelled ATP in vitro. Separation of proteins on SDS slab gels indicated up to 30 protein bands stained by Coomassie blue of which ten incorporated label, as detected by radioautography (mol. wt. range 16-110 K with a major double band at 49-50 K). Incorporation into the 110 K region appeared to increase in older persons, and that into the 49-50 K region decreased. Human but not rat membranes subjected to similar conditions of treatment failed to respond to the addition of cAMP at 10(-5) - 10(-7) M but were highly sensitive to the addition of cGMP at 10(-6) M, which led to intensification of existing bands and the appearance of a major band at 60 K. The 110 K band present in high concentration in white matter striatum, caudate nucleus, and putamen was insensitive to cGMP addition. The presence of cGMP-dependent protein kinase substrates has not previously been reported in synapses, and it may be of significance in view of the known sensitivity of this system to biological regulatory agents."}
{"id": "PMID:233778", "title": "Involvement of cholecalciferol metabolism in birds in the adaptation of calcium absorption to the needs during reproduction.", "content": "1. The metabolism of calcium and cholecalciferol in quail (Coturnix coturnix japonica) and chicken (Gallus domesticus) during maturation was correlated to gonadal activity and plasma oestrogen levels. 2. Birds with undeveloped ovaries (immature), developed ovaries but not laying (mature), and after laying 3-8 eggs (laying), were used in the first series. 3. Birds in which egg production had been arrested by Nicarbazin, were used in the second series. 4. Plasma 17 beta-oestradiol and calcium were elevated in the mature bird, with no further change in the laying bird. Kidney 25-hydroxycholecalciferol-1-hydroxylase and intestinal calcium-binding protein increased slightly in the mature bird, whereas they were grossly elevated in the laying bird. 5. Calcium and phosphorus absorption were markedly elevated in the laying bird. 6. No changes were noted in plasma 25-hydroxycholecalciferol, at any stage of maturation. 7. During the arrest of egg production by Nicarbazin, 17 beta-oestradiol level, calcium concentration of plasma, and medullary bone were maintained. Kidney 25-hydroxy-cholecalciferol-1-hydroxylase, intestinal calcium-binding protein and absorption of calcium were strikingly reduced. 8. The results suggest that changes in calcium absorption and cholecalciferol metabolism during maturation in birds are not directly affected by gonadal hormones; they appear to represent an adaptation to the increased calcium needs due to medullary bone formation and, more importantly, to the large losses of calcium imposed by shell formation.", "contents": "Involvement of cholecalciferol metabolism in birds in the adaptation of calcium absorption to the needs during reproduction. 1. The metabolism of calcium and cholecalciferol in quail (Coturnix coturnix japonica) and chicken (Gallus domesticus) during maturation was correlated to gonadal activity and plasma oestrogen levels. 2. Birds with undeveloped ovaries (immature), developed ovaries but not laying (mature), and after laying 3-8 eggs (laying), were used in the first series. 3. Birds in which egg production had been arrested by Nicarbazin, were used in the second series. 4. Plasma 17 beta-oestradiol and calcium were elevated in the mature bird, with no further change in the laying bird. Kidney 25-hydroxycholecalciferol-1-hydroxylase and intestinal calcium-binding protein increased slightly in the mature bird, whereas they were grossly elevated in the laying bird. 5. Calcium and phosphorus absorption were markedly elevated in the laying bird. 6. No changes were noted in plasma 25-hydroxycholecalciferol, at any stage of maturation. 7. During the arrest of egg production by Nicarbazin, 17 beta-oestradiol level, calcium concentration of plasma, and medullary bone were maintained. Kidney 25-hydroxy-cholecalciferol-1-hydroxylase, intestinal calcium-binding protein and absorption of calcium were strikingly reduced. 8. The results suggest that changes in calcium absorption and cholecalciferol metabolism during maturation in birds are not directly affected by gonadal hormones; they appear to represent an adaptation to the increased calcium needs due to medullary bone formation and, more importantly, to the large losses of calcium imposed by shell formation."}
{"id": "PMID:233779", "title": "A study of bovid herpesvirus 2 infection in calves inoculated intradermally or intranasally.", "content": "Bovid herpesvirus 2 infection was studied in calves exposed to the virus by intradermal inoculation of the skin of the left cheek or by nasal spray. In either case a localised infection developed and virus replication was shown to occur mostly in the tissues of its primary localisation, i.e. the skin of the left cheek or the nasal mucosa. There were neither secondary lesions, except at the site of virus injection, nor any serious systemic involvement on the part of the animals. The virus was also recovered from some areas of the skin (right cheek, perineum and scrotum) that were free of macroscopic lesions; moreover, intranuclear inclusions were found in several tissues of the nervous system (brain, superior cervical, stellate and Gasserian ganglia) which did not show any signs of inflammatory or degenerative changes. These findings suggest that the skin and the nervous system play an important role in the naturally-occurring disease since they could be the sites where the virus is maintained latently in the host.", "contents": "A study of bovid herpesvirus 2 infection in calves inoculated intradermally or intranasally. Bovid herpesvirus 2 infection was studied in calves exposed to the virus by intradermal inoculation of the skin of the left cheek or by nasal spray. In either case a localised infection developed and virus replication was shown to occur mostly in the tissues of its primary localisation, i.e. the skin of the left cheek or the nasal mucosa. There were neither secondary lesions, except at the site of virus injection, nor any serious systemic involvement on the part of the animals. The virus was also recovered from some areas of the skin (right cheek, perineum and scrotum) that were free of macroscopic lesions; moreover, intranuclear inclusions were found in several tissues of the nervous system (brain, superior cervical, stellate and Gasserian ganglia) which did not show any signs of inflammatory or degenerative changes. These findings suggest that the skin and the nervous system play an important role in the naturally-occurring disease since they could be the sites where the virus is maintained latently in the host."}
{"id": "PMID:233780", "title": "A new freeze-dried living virus vaccine against sheep-pox.", "content": "A sheep-pox virus strain has been adapted and multiplied in primary lamb kidney cell cultures. The main characteristics of the strain have been verified in vitro after clones were isolated, and the results confirmed its identity. The safety and the potency of the strain have been investigated in sheep. The inoculation of the strain to sheep was followed by a post-vaccinal reaction materialised by a nodule at the site of inoculation and an increase of temperature by about 1 degree C. No reactions adversely affecting pregnancy have been noted. Immunisation was demonstrated by an increase in the level of neutralising serous antibodies and protection against the pathogenic virus. The immunity tended to decrease during the second year after primovaccination and a yearly booster vaccination appeared to be necessary. Primovaccination of lambs over 2 months of age produced a better immunity, especially when the lambs were born from vaccinated ewes. This strain forms the active principle of a freeze-dried vaccine containing no adjuvant of the immunity.", "contents": "A new freeze-dried living virus vaccine against sheep-pox. A sheep-pox virus strain has been adapted and multiplied in primary lamb kidney cell cultures. The main characteristics of the strain have been verified in vitro after clones were isolated, and the results confirmed its identity. The safety and the potency of the strain have been investigated in sheep. The inoculation of the strain to sheep was followed by a post-vaccinal reaction materialised by a nodule at the site of inoculation and an increase of temperature by about 1 degree C. No reactions adversely affecting pregnancy have been noted. Immunisation was demonstrated by an increase in the level of neutralising serous antibodies and protection against the pathogenic virus. The immunity tended to decrease during the second year after primovaccination and a yearly booster vaccination appeared to be necessary. Primovaccination of lambs over 2 months of age produced a better immunity, especially when the lambs were born from vaccinated ewes. This strain forms the active principle of a freeze-dried vaccine containing no adjuvant of the immunity."}
{"id": "PMID:233781", "title": "Immunisation against panleukopenia: early development of immunity.", "content": "The time necessary to obtain the immunity of cats against Panleukopenia has been studied by means of a modified live vaccine. This vaccine makes it possible to obtain a very early post-vaccinal immunity: the full immunity is reached 72 hr after the inoculation of the vaccine by the subcutaneous route. Furthermore, we have demonstrated that a sensitive kitten can be admitted in a contaminated environment immediately after vaccination without showing any clinical evidence of the disease.", "contents": "Immunisation against panleukopenia: early development of immunity. The time necessary to obtain the immunity of cats against Panleukopenia has been studied by means of a modified live vaccine. This vaccine makes it possible to obtain a very early post-vaccinal immunity: the full immunity is reached 72 hr after the inoculation of the vaccine by the subcutaneous route. Furthermore, we have demonstrated that a sensitive kitten can be admitted in a contaminated environment immediately after vaccination without showing any clinical evidence of the disease."}
{"id": "PMID:233782", "title": "Bovine adenoviruses--IV. Two mixed antigens for routine serodiagnosis by complement fixation reaction.", "content": "The frequency of bovine adenovirus infections occurring in cattle has been grossly underestimated up to the present day. Primary isolation of serotypes belonging to bovine subgroup II is cumbersome. Hardly any laboratory has used all 8 officially-recognised bovine serotypes in seroneutralisation-tests, which should be done when this type-specific method is used for serodiagnosis. The complement fixation test, known as group-reactive from human adenovirus serology, has failed to disclose the true incidence of bovine infections, as until recently the importance of a novel additional group-reactive bovine adenovirus antigen has been undisclosed. Here we describe production, composition and performance of two mixed antigens for complement fixation reactions, which take into account recent findings by our team on peculiarities of bovine adenovirus antigens. Mixed antigen 1 contains bovine serotypes 1, 2 and 3 and detects group-specific antibodies of the classical mastadenoviruses. Mixed antigen 2 contains bovine serotypes 4, 5, 6, 7 and 8 and determines group-specific antibodies against the novel paramastadenoviruses. In addition, each antigen is capable of demonstrating complement-fixing type-specific antibodies in sera against the respective types included in each mixed antigen, with a net enhancing effect produced by mixing. Use of the 2 mixed antigens promptly shows whether bovine adenoviruses, presently recognised as well as unclassified, are involved in a given outbreak of respiratory or enteric disease of cattle. If needed, the responsible type may be determined in a second step of serological investigation.", "contents": "Bovine adenoviruses--IV. Two mixed antigens for routine serodiagnosis by complement fixation reaction. The frequency of bovine adenovirus infections occurring in cattle has been grossly underestimated up to the present day. Primary isolation of serotypes belonging to bovine subgroup II is cumbersome. Hardly any laboratory has used all 8 officially-recognised bovine serotypes in seroneutralisation-tests, which should be done when this type-specific method is used for serodiagnosis. The complement fixation test, known as group-reactive from human adenovirus serology, has failed to disclose the true incidence of bovine infections, as until recently the importance of a novel additional group-reactive bovine adenovirus antigen has been undisclosed. Here we describe production, composition and performance of two mixed antigens for complement fixation reactions, which take into account recent findings by our team on peculiarities of bovine adenovirus antigens. Mixed antigen 1 contains bovine serotypes 1, 2 and 3 and detects group-specific antibodies of the classical mastadenoviruses. Mixed antigen 2 contains bovine serotypes 4, 5, 6, 7 and 8 and determines group-specific antibodies against the novel paramastadenoviruses. In addition, each antigen is capable of demonstrating complement-fixing type-specific antibodies in sera against the respective types included in each mixed antigen, with a net enhancing effect produced by mixing. Use of the 2 mixed antigens promptly shows whether bovine adenoviruses, presently recognised as well as unclassified, are involved in a given outbreak of respiratory or enteric disease of cattle. If needed, the responsible type may be determined in a second step of serological investigation."}
{"id": "PMID:233783", "title": "Carbohydrate composition of serum low and high density lipoproteins of nonhuman primate species.", "content": "1. Carbohydrate composition of serum low and high density lipoproteins obtained from 5 nonhuman primate species (chimpanzee, patas, baboon, rhesus, and spider) and humans was studied. 2. Individual lipoproteins were isolated from pooled sera of each species by ultracentrifugal flotation between the densities 1.019-1.063 for LDL-2; 1.063-1.12 for HDL-2; and 1.12-1.21 for HDL-3. After delipidation, sialic acid, fucose, glucosamine, mannose, galactose, and glucose were determined on apo LDL-2, apo HDL-2, and apo HDL-3. 3. Glucosamine, galactose, and mannose constituted a major component of the sugars in apo LDL-2, with similar relative proportions in all species. Sialic acid, fucose, and glucose formed a minor component, the proportions of which varied greatly among the species. 4. Unlike apo LDL-2, sialic acid, fucose, and glucosamine constituted the bulk of the sugars in apo HDL-2 and apo HDL-3. Mannose, galactose, and glucose were minor components, with galactose predominating. 5. Qualitative differences were observed in electrophoretic mobilities of apo HDL-2 and apo HDL-3 on polyacrylamide gel. One faster moving band was unique to chimpanzee. 6. Intraspecies differences in the content of sialic acid and fucose of apolipoproteins may be related to lipoprotein metabolism and species susceptibility (or resistance) to either spontaneous or diet-induced atherosclerosis.", "contents": "Carbohydrate composition of serum low and high density lipoproteins of nonhuman primate species. 1. Carbohydrate composition of serum low and high density lipoproteins obtained from 5 nonhuman primate species (chimpanzee, patas, baboon, rhesus, and spider) and humans was studied. 2. Individual lipoproteins were isolated from pooled sera of each species by ultracentrifugal flotation between the densities 1.019-1.063 for LDL-2; 1.063-1.12 for HDL-2; and 1.12-1.21 for HDL-3. After delipidation, sialic acid, fucose, glucosamine, mannose, galactose, and glucose were determined on apo LDL-2, apo HDL-2, and apo HDL-3. 3. Glucosamine, galactose, and mannose constituted a major component of the sugars in apo LDL-2, with similar relative proportions in all species. Sialic acid, fucose, and glucose formed a minor component, the proportions of which varied greatly among the species. 4. Unlike apo LDL-2, sialic acid, fucose, and glucosamine constituted the bulk of the sugars in apo HDL-2 and apo HDL-3. Mannose, galactose, and glucose were minor components, with galactose predominating. 5. Qualitative differences were observed in electrophoretic mobilities of apo HDL-2 and apo HDL-3 on polyacrylamide gel. One faster moving band was unique to chimpanzee. 6. Intraspecies differences in the content of sialic acid and fucose of apolipoproteins may be related to lipoprotein metabolism and species susceptibility (or resistance) to either spontaneous or diet-induced atherosclerosis."}
{"id": "PMID:233784", "title": "A comparative study of some more important experimental animal peroxide metabolism enzymes.", "content": "1. We have studied and compared the peroxide metabolism enzymes (SOD, P and C) of the main organs of fresh-water mollusc, chicken, mouse, guinea-pig, rabbit, cat and dog. 2. The liver exhibited the highest SOD activity. The enzymatic activities of the organ homogenates of the guinea-pig stand out in comparison with the values for the other homogenates examined. 3. The liver, kidney and total brain homogenates of the chicken and the vertebrates display no, or only a very low P activity. The highest P activities were measured in the haemolysates. 4. The C and SOD values exhibit a certain parallelism. 5. The peroxide metabolism enzyme activities calculated by utilizing the protein measurements permit the establishment of a more realistic enzymatic activity.", "contents": "A comparative study of some more important experimental animal peroxide metabolism enzymes. 1. We have studied and compared the peroxide metabolism enzymes (SOD, P and C) of the main organs of fresh-water mollusc, chicken, mouse, guinea-pig, rabbit, cat and dog. 2. The liver exhibited the highest SOD activity. The enzymatic activities of the organ homogenates of the guinea-pig stand out in comparison with the values for the other homogenates examined. 3. The liver, kidney and total brain homogenates of the chicken and the vertebrates display no, or only a very low P activity. The highest P activities were measured in the haemolysates. 4. The C and SOD values exhibit a certain parallelism. 5. The peroxide metabolism enzyme activities calculated by utilizing the protein measurements permit the establishment of a more realistic enzymatic activity."}
{"id": "PMID:233785", "title": "Enzymes of galactose utilization in the rat tapeworm, Hymenolepis diminuta.", "content": "1. Crude enzyme preparations from Hymenolepis diminuta contained galactokinase, galactose 1-phosphate uridyl transferase and UDPgalactose 4-epimerase activity, although their specific activities were low. 2. Galactose 1-phosphate non-competitively inhibited galactose phosphorylation. This inhibition, together with the low specific activities of the enzymes in the pathway of galactose utilization, probably accounts for the inadequacy of galactose as a main nutritive carbohydrate for development of the worm.", "contents": "Enzymes of galactose utilization in the rat tapeworm, Hymenolepis diminuta. 1. Crude enzyme preparations from Hymenolepis diminuta contained galactokinase, galactose 1-phosphate uridyl transferase and UDPgalactose 4-epimerase activity, although their specific activities were low. 2. Galactose 1-phosphate non-competitively inhibited galactose phosphorylation. This inhibition, together with the low specific activities of the enzymes in the pathway of galactose utilization, probably accounts for the inadequacy of galactose as a main nutritive carbohydrate for development of the worm."}
{"id": "PMID:233786", "title": "Differential lipid control of (Na+ + K+)-ATPase in homeotherms and poikilotherms.", "content": "1. (Na+ + K+)-ATPase from homeotherms and poikilotherms demonstrate non-linear thermal dependence for ATP hydrolysis. Apparent energies of activation from crab nerve preparations are less than those of brain or kidney preparations from beef, rabbit, sheep or ground squirrel. 2. Crab nerve (Na+ + K+)-ATPase is less sensitive to inhibition by ouabain than that from beef or ground squirrel; lower rates of [3H]-ouabain binding and reduced amount of drug bound at equilibrium are found. 3. K+-activated acyl-phosphatase is similar in all preparations. 4. Fluorescence polarization of 12-AS labelled membranes demonstrate greater mobility of crab nerve lipids compared to beef brain which has a thermal transition at 20-25 degrees C. Crab nerve is linear in this range.", "contents": "Differential lipid control of (Na+ + K+)-ATPase in homeotherms and poikilotherms. 1. (Na+ + K+)-ATPase from homeotherms and poikilotherms demonstrate non-linear thermal dependence for ATP hydrolysis. Apparent energies of activation from crab nerve preparations are less than those of brain or kidney preparations from beef, rabbit, sheep or ground squirrel. 2. Crab nerve (Na+ + K+)-ATPase is less sensitive to inhibition by ouabain than that from beef or ground squirrel; lower rates of [3H]-ouabain binding and reduced amount of drug bound at equilibrium are found. 3. K+-activated acyl-phosphatase is similar in all preparations. 4. Fluorescence polarization of 12-AS labelled membranes demonstrate greater mobility of crab nerve lipids compared to beef brain which has a thermal transition at 20-25 degrees C. Crab nerve is linear in this range."}
{"id": "PMID:233787", "title": "Glucose phosphorylation and dephosphorylation in chicken liver.", "content": "1. Glucokinase was absent from chicken liver and only the low Km hexokinases, inhibited by AMP, ADP but not ATP, were present. 2. The Km of chicken liver glucose-6-phosphatase for glucose-6-phosphate was reduced from 5.65 to 3.75 mM following starvation, and the enzyme was inhibited by glucose. 3. Starvation of chickens for 24 hr slightly lowered the hexokinase activity and doubled glucose-6-phosphatase activity; it did not change subcellular distribution of the enzymes. Oral glucose rapidly restored the activities to fed values. 4. It was concluded that glucose uptake into, and efflux from, chicken hepatocytes, was regulated by the activity and kinetic characteristics of glucose-6-phosphatase and by the glucose-6-phosphate concentration, and that the hexokinases had little regulatory function.", "contents": "Glucose phosphorylation and dephosphorylation in chicken liver. 1. Glucokinase was absent from chicken liver and only the low Km hexokinases, inhibited by AMP, ADP but not ATP, were present. 2. The Km of chicken liver glucose-6-phosphatase for glucose-6-phosphate was reduced from 5.65 to 3.75 mM following starvation, and the enzyme was inhibited by glucose. 3. Starvation of chickens for 24 hr slightly lowered the hexokinase activity and doubled glucose-6-phosphatase activity; it did not change subcellular distribution of the enzymes. Oral glucose rapidly restored the activities to fed values. 4. It was concluded that glucose uptake into, and efflux from, chicken hepatocytes, was regulated by the activity and kinetic characteristics of glucose-6-phosphatase and by the glucose-6-phosphate concentration, and that the hexokinases had little regulatory function."}
{"id": "PMID:233788", "title": "Regulation of carbohydrate metabolism in mouse liver. Effect of glucagon on gluconeogenic/glycolytic flux in isolated perfused livers.", "content": "1. Glucagon stimulated gluconeogenesis from both [U-14C]lactate and [14C]xylitol in isolated perfused mouse liver. 2. Addition of cyclic AMP also stimulated gluconeogenesis from [U-14C]lactate. 3. Glucagon caused a rapid (2.5 min) 12-fold increase in hepatic cyclic AMP but not cyclic GMP concentration. 4. Glucagon caused a rapid and stable decrease in hepatic fructose 1,6-diphosphatase activity measured in vitro. 5. The results are interpreted to indicate that glucagon stimulates hepatic gluconeogenesis in mice via cyclic AMP by two different mechanisms: (a) increased substrate uptake (i.e. utilization) and (b) increased gluconeogenic efficiency (i.e. inhibition of alternate substrate fates).", "contents": "Regulation of carbohydrate metabolism in mouse liver. Effect of glucagon on gluconeogenic/glycolytic flux in isolated perfused livers. 1. Glucagon stimulated gluconeogenesis from both [U-14C]lactate and [14C]xylitol in isolated perfused mouse liver. 2. Addition of cyclic AMP also stimulated gluconeogenesis from [U-14C]lactate. 3. Glucagon caused a rapid (2.5 min) 12-fold increase in hepatic cyclic AMP but not cyclic GMP concentration. 4. Glucagon caused a rapid and stable decrease in hepatic fructose 1,6-diphosphatase activity measured in vitro. 5. The results are interpreted to indicate that glucagon stimulates hepatic gluconeogenesis in mice via cyclic AMP by two different mechanisms: (a) increased substrate uptake (i.e. utilization) and (b) increased gluconeogenic efficiency (i.e. inhibition of alternate substrate fates)."}
{"id": "PMID:233789", "title": "The effects of ACTH on adrenal steroidogenesis and blood corticosteroid levels in the echidna (Tachyglossus aculeatus).", "content": "1. The effects of short-term (S.T., 30 min) and long-term (L.T., 4 days) administration of ACTH on peripheral blood corticosteroid levels and on in vitro steroidogenesis were investigated. 2. Control levels of cortisol, corticosterone and aldosterone were 58 +/- 12, 130 +/- 26 and 10 +/- 6 (SEM) ng/100 ml respectively. 3. Corticosterone was 70% higher after S.T. and 150% higher after L.T., when cortisol was 800% higher. 4. Adrenal homogenates from control echidnas converted [14C]progesterone predominantly to 11-deoxycorticosterone (45%) and 11-deoxycortisol (12%). 5. After L.T. the principal product was corticosterone (25%), but S.T. had no effect. 6. In control echidnas the Km and V for 11 beta-hydroxylation of 11-deoxycorticosterone were 20 microM and 2.8 rho mol/min/mg respectively. After L.T. V increased to 10 rho mol/min/mg.", "contents": "The effects of ACTH on adrenal steroidogenesis and blood corticosteroid levels in the echidna (Tachyglossus aculeatus). 1. The effects of short-term (S.T., 30 min) and long-term (L.T., 4 days) administration of ACTH on peripheral blood corticosteroid levels and on in vitro steroidogenesis were investigated. 2. Control levels of cortisol, corticosterone and aldosterone were 58 +/- 12, 130 +/- 26 and 10 +/- 6 (SEM) ng/100 ml respectively. 3. Corticosterone was 70% higher after S.T. and 150% higher after L.T., when cortisol was 800% higher. 4. Adrenal homogenates from control echidnas converted [14C]progesterone predominantly to 11-deoxycorticosterone (45%) and 11-deoxycortisol (12%). 5. After L.T. the principal product was corticosterone (25%), but S.T. had no effect. 6. In control echidnas the Km and V for 11 beta-hydroxylation of 11-deoxycorticosterone were 20 microM and 2.8 rho mol/min/mg respectively. After L.T. V increased to 10 rho mol/min/mg."}
{"id": "PMID:233790", "title": "Biochemical studies of taste sensation--VIII. Partial characterization of alanine-binding taste receptor sites of catfish Ictalurus punctatus using mercurials, sulfhydryl reagents, trypsin and phospholipase C.", "content": "1. Taste receptors for L-alanine in the channel catfish Ictalurus punctatus have been partially characterized. The binding activity, which is localized to a sedimentable fraction (Fraction P2), was assayed with L-[3H]alanine as the ligand. 2. Addition of HgCl2 or p-mercuribenzoate to the assay at 0.1-1 mM markedly inhibited binding. The effect was not reversible and was unaffected by increased L-alanine in the binding assay. 3. The sulfhydryl reagents iodoacetate, 5,5'-dithiobis(2-nitrobenzoic acid), arsenite, and N-ethylmaleimide did not show appreciable inhibition of binding. The results suggest that the inhibitory effect of mercurials is not on specific sulfhydryl groups at alanine-binding sites. 4. Treatment of Fraction P2 with phospholipase C decreased binding activity and treatment with trypsin led to increased binding activity.", "contents": "Biochemical studies of taste sensation--VIII. Partial characterization of alanine-binding taste receptor sites of catfish Ictalurus punctatus using mercurials, sulfhydryl reagents, trypsin and phospholipase C. 1. Taste receptors for L-alanine in the channel catfish Ictalurus punctatus have been partially characterized. The binding activity, which is localized to a sedimentable fraction (Fraction P2), was assayed with L-[3H]alanine as the ligand. 2. Addition of HgCl2 or p-mercuribenzoate to the assay at 0.1-1 mM markedly inhibited binding. The effect was not reversible and was unaffected by increased L-alanine in the binding assay. 3. The sulfhydryl reagents iodoacetate, 5,5'-dithiobis(2-nitrobenzoic acid), arsenite, and N-ethylmaleimide did not show appreciable inhibition of binding. The results suggest that the inhibitory effect of mercurials is not on specific sulfhydryl groups at alanine-binding sites. 4. Treatment of Fraction P2 with phospholipase C decreased binding activity and treatment with trypsin led to increased binding activity."}
{"id": "PMID:233791", "title": "Zinc effects on LDH, MDH and alkaline phosphatase from cultures of fathead minnow cells.", "content": "1. Three purported zinc metalloenzymes have been investigated from cell cultures of the fathead minnow (Pimephales promelas). 2. With the addition of increasingly higher concentrations of zinc to the tissue culture medium, the specific activity of LDH increased. 3. The results with MDH were equivocal. 4. The specific activity of alkaline phosphatase decreased in the presence of increasing amounts of zinc in the growth medium. 5. Zinc exogenously added to the LDH enzyme assay did not alter the LDH enzyme activity of cells grown without zinc.", "contents": "Zinc effects on LDH, MDH and alkaline phosphatase from cultures of fathead minnow cells. 1. Three purported zinc metalloenzymes have been investigated from cell cultures of the fathead minnow (Pimephales promelas). 2. With the addition of increasingly higher concentrations of zinc to the tissue culture medium, the specific activity of LDH increased. 3. The results with MDH were equivocal. 4. The specific activity of alkaline phosphatase decreased in the presence of increasing amounts of zinc in the growth medium. 5. Zinc exogenously added to the LDH enzyme assay did not alter the LDH enzyme activity of cells grown without zinc."}
{"id": "PMID:233792", "title": "Lipid and carbohydrate metabolism in euthyroid and hypothyroid chick embryo (Gallus domesticus).", "content": "1. The effect of propylthiouracil (PTU)-induced hypothyroidism on carbohydrate and lipid metabolism was studied in the chick embryo. 2. A single dose of PTU (250 micrograms/embryo) was administered on day 11 and embryos sacrificed on day 20 of incubation. 3. Thyroid glands were significantly enlarged (6 fold) by PTU administration. 4. Increased thyroid weight was associated with growth retardation and decreased plasma thyroxine levels. 5. Plasma glucose level was lower and phospholipids were significantly higher in the hypothyroid embryo. 6. Liver lipid concentrations in the control and hypothyroid embryos were not different but were significantly higher in both groups when compared to previously reported values in the young chick. 7. In contrast to PTU treatment after hatching, liver glycogen levels were not increased in the hypothyroid chick embryo. This was attributed to the high lipid nutrient condition of the chick embryo since a high lipid diet in the young chick decreased hepatic glycogen accumulation significantly.", "contents": "Lipid and carbohydrate metabolism in euthyroid and hypothyroid chick embryo (Gallus domesticus). 1. The effect of propylthiouracil (PTU)-induced hypothyroidism on carbohydrate and lipid metabolism was studied in the chick embryo. 2. A single dose of PTU (250 micrograms/embryo) was administered on day 11 and embryos sacrificed on day 20 of incubation. 3. Thyroid glands were significantly enlarged (6 fold) by PTU administration. 4. Increased thyroid weight was associated with growth retardation and decreased plasma thyroxine levels. 5. Plasma glucose level was lower and phospholipids were significantly higher in the hypothyroid embryo. 6. Liver lipid concentrations in the control and hypothyroid embryos were not different but were significantly higher in both groups when compared to previously reported values in the young chick. 7. In contrast to PTU treatment after hatching, liver glycogen levels were not increased in the hypothyroid chick embryo. This was attributed to the high lipid nutrient condition of the chick embryo since a high lipid diet in the young chick decreased hepatic glycogen accumulation significantly."}
{"id": "PMID:233793", "title": "Ascorbic acid-dependent collagen formation in penaeid shrimp.", "content": "1. This study tested the hypothesis that black death, the ascorbic acid (AsA) related disease of penaeid shrimp, is related to collagen underhydroxylation. 2. Collagen measured as hydroxyproline (HYP) in healthy Penaeus californiensis (Holmes) and P. stylirostris (Stimpson) of a wide range of masses were determined. The results revealed a logarithmic relationship between total body collagen HYP and body weight fitting the equation y = 90x1.18 where y = total collagenous HYP (microgram) and x = body weight (g). 3. Shrimp tissues most subject to mechanical trauma (subcutis, hindgut and gills) had the highest collagenous HYP levels and were most consistently and severely affected by an ascorbic acid (AsA) deficiency disease. 4. Prolyl hydroxylase (PH) activity was demonstrated in tissues of P. californiensis and P. stylirostris by hydroxylation of [3,4-3H]proline. 5. AsA was required for shrimp PH activity using a chicken embryo substrate. 6. Nutritional trials revealed that dietary AsA was required for proline hydroxylation in collagen formation in P. californiensis.", "contents": "Ascorbic acid-dependent collagen formation in penaeid shrimp. 1. This study tested the hypothesis that black death, the ascorbic acid (AsA) related disease of penaeid shrimp, is related to collagen underhydroxylation. 2. Collagen measured as hydroxyproline (HYP) in healthy Penaeus californiensis (Holmes) and P. stylirostris (Stimpson) of a wide range of masses were determined. The results revealed a logarithmic relationship between total body collagen HYP and body weight fitting the equation y = 90x1.18 where y = total collagenous HYP (microgram) and x = body weight (g). 3. Shrimp tissues most subject to mechanical trauma (subcutis, hindgut and gills) had the highest collagenous HYP levels and were most consistently and severely affected by an ascorbic acid (AsA) deficiency disease. 4. Prolyl hydroxylase (PH) activity was demonstrated in tissues of P. californiensis and P. stylirostris by hydroxylation of [3,4-3H]proline. 5. AsA was required for shrimp PH activity using a chicken embryo substrate. 6. Nutritional trials revealed that dietary AsA was required for proline hydroxylation in collagen formation in P. californiensis."}
{"id": "PMID:233794", "title": "Effects of 5-hydroxytryptophan on fragmentation of REM sleep in alcoholics.", "content": "The authors studied the effects of oral loading with 5-HTP on REM fragmentation in a group of alcoholics who were abstinent following acute ethanol withdrawal. Decreased fragmentation was found in the majority of subjects, and those subjects with low baseline REM efficiency (i.e., greater fragmentation) showed more improvement from the drug than did subjects who were less impaired initially. The authors suggest that there is an organic decrement of serotonin during ethanol withdrawal which is partially reversed by 5-HTP loading.", "contents": "Effects of 5-hydroxytryptophan on fragmentation of REM sleep in alcoholics. The authors studied the effects of oral loading with 5-HTP on REM fragmentation in a group of alcoholics who were abstinent following acute ethanol withdrawal. Decreased fragmentation was found in the majority of subjects, and those subjects with low baseline REM efficiency (i.e., greater fragmentation) showed more improvement from the drug than did subjects who were less impaired initially. The authors suggest that there is an organic decrement of serotonin during ethanol withdrawal which is partially reversed by 5-HTP loading."}
{"id": "PMID:233795", "title": "Determination of adenosine 3',5'-cyclic monophosphate levels in tissues of the free living nematode, Panagrellus redivivus.", "content": "1. Tissue levels of adenosine 3', 5'-cyclic monophosphate (c-AMP) were determined by a protein binding assay in mixed populations of the free living nematode Panagrellus redivivus. 2. The values were 2.6 pmoles/mg dry weight (range 1.3-3.4 pmoles). 3. The identity of the c-AMP assayed was confirmed by both anion exchange and TLC as well as enzymatic degradation.", "contents": "Determination of adenosine 3',5'-cyclic monophosphate levels in tissues of the free living nematode, Panagrellus redivivus. 1. Tissue levels of adenosine 3', 5'-cyclic monophosphate (c-AMP) were determined by a protein binding assay in mixed populations of the free living nematode Panagrellus redivivus. 2. The values were 2.6 pmoles/mg dry weight (range 1.3-3.4 pmoles). 3. The identity of the c-AMP assayed was confirmed by both anion exchange and TLC as well as enzymatic degradation."}
{"id": "PMID:233796", "title": "Seasonal variations in the renal cortical (Na+ + K+)-ATPase and Mg2+-ATPase of a hibernator, the ground squirrel (Spermophilus richardsonii).", "content": "1. The specific activity of renal cortical (Na+ + K+)-ATPase of the Richardson ground squirrel is markedly reduced during hibernation, in contrast to the specific activity of the accompanying Mg2+-ATPase which is markedly increased. 2. The sensitivity of (Na+ + K+)-ATPase to inhibition by ouabain is unchanged by hibernation. 3. Both the non-linear thermal dependence of (Na+ + K+)-ATPase and the linear thermal dependence of Mg2+-ATPase are also unchanged by hibernation. 4. The energy of activation of both enzymes is unchanged during hibernation, or by comparison with that determined in awake controls. 5. There is no evidence for inherent \"cold resistance\" in these enzyme preparations compared to similar preparations from the non-hibernating rabbit. This parameter does not change during hibernation. 6. Both the rate and amount of specific [3H]-ouabain binding to the renal cortical preparations of (Na+ + K+)-ATPase decrease during hibernation. This decrease matches the fall in enzyme activity so that the ratio of pumping sites/unit of enzyme activity shows no seasonal variations. 7. These findings suggest that the amount of renal cortical (Na+ + K+)-ATPase enzyme falls during hibernation, but that the enzyme which remains functions with the same thermodynamic efficiency and identical biochemical characteristics of that found in the awake summer controls.", "contents": "Seasonal variations in the renal cortical (Na+ + K+)-ATPase and Mg2+-ATPase of a hibernator, the ground squirrel (Spermophilus richardsonii). 1. The specific activity of renal cortical (Na+ + K+)-ATPase of the Richardson ground squirrel is markedly reduced during hibernation, in contrast to the specific activity of the accompanying Mg2+-ATPase which is markedly increased. 2. The sensitivity of (Na+ + K+)-ATPase to inhibition by ouabain is unchanged by hibernation. 3. Both the non-linear thermal dependence of (Na+ + K+)-ATPase and the linear thermal dependence of Mg2+-ATPase are also unchanged by hibernation. 4. The energy of activation of both enzymes is unchanged during hibernation, or by comparison with that determined in awake controls. 5. There is no evidence for inherent \"cold resistance\" in these enzyme preparations compared to similar preparations from the non-hibernating rabbit. This parameter does not change during hibernation. 6. Both the rate and amount of specific [3H]-ouabain binding to the renal cortical preparations of (Na+ + K+)-ATPase decrease during hibernation. This decrease matches the fall in enzyme activity so that the ratio of pumping sites/unit of enzyme activity shows no seasonal variations. 7. These findings suggest that the amount of renal cortical (Na+ + K+)-ATPase enzyme falls during hibernation, but that the enzyme which remains functions with the same thermodynamic efficiency and identical biochemical characteristics of that found in the awake summer controls."}
{"id": "PMID:233797", "title": "Difference in renal alpha-galactosidase levels in male and female Chinese hamsters (Cricetulus griseus).", "content": "1. The activity of alpha-galactosidase was found to be significantly higher in the kidney of female than that of male Chinese hamsters in a highly inbred colony but its activity in liver, heart and spleen remained similar between female and male animals. 2. Partially purified renal alpha-galactosidase by sequential column chromatography on Sepharose 6B and DEAE-Sepharose CL-6B showed identical elution profiles, pH optima (4.5), KmS (4.4 mM) and heat-inactivation curves between enzymes of male and female animals. 3. Thus, the observed higher activity of renal alpha-galactosidase in the females was due to elevated enzyme concentration, not a result of enzyme polymorphism.", "contents": "Difference in renal alpha-galactosidase levels in male and female Chinese hamsters (Cricetulus griseus). 1. The activity of alpha-galactosidase was found to be significantly higher in the kidney of female than that of male Chinese hamsters in a highly inbred colony but its activity in liver, heart and spleen remained similar between female and male animals. 2. Partially purified renal alpha-galactosidase by sequential column chromatography on Sepharose 6B and DEAE-Sepharose CL-6B showed identical elution profiles, pH optima (4.5), KmS (4.4 mM) and heat-inactivation curves between enzymes of male and female animals. 3. Thus, the observed higher activity of renal alpha-galactosidase in the females was due to elevated enzyme concentration, not a result of enzyme polymorphism."}
{"id": "PMID:233798", "title": "NAD glycohydrolase activity in dog cardiac tissue.", "content": "1. Dog heart tissue suspension hydrolyzes NAD, NADP and NMN, and releases nicotinamide stoichiometrically. 2. Maximum activity was observed at 50 degrees C and the activation energy was 10 kcal/mol. 3. Optimum pH range was 6.2-7.6. 4. Compounds with adenine-ribose moiety increased the enzymatic activity. 5. Nicotinamide released during incubation produced reaction nonlinearity. 6. Km for NAD and NADP were about the same; Vmax was higher for NAD. Similar findings have been reported for rabbit heart. 7. Dog enzyme appears to be more sensitive than the rabbit enzyme to noncompetitive inhibitors. 8. Pyrophosphatase activity was not detected in dog heart in contrast to rabbit and rat heart preparations.", "contents": "NAD glycohydrolase activity in dog cardiac tissue. 1. Dog heart tissue suspension hydrolyzes NAD, NADP and NMN, and releases nicotinamide stoichiometrically. 2. Maximum activity was observed at 50 degrees C and the activation energy was 10 kcal/mol. 3. Optimum pH range was 6.2-7.6. 4. Compounds with adenine-ribose moiety increased the enzymatic activity. 5. Nicotinamide released during incubation produced reaction nonlinearity. 6. Km for NAD and NADP were about the same; Vmax was higher for NAD. Similar findings have been reported for rabbit heart. 7. Dog enzyme appears to be more sensitive than the rabbit enzyme to noncompetitive inhibitors. 8. Pyrophosphatase activity was not detected in dog heart in contrast to rabbit and rat heart preparations."}
{"id": "PMID:233799", "title": "Determination of guanosine 3',5'-cyclic-monophosphate in tissues of the free living nematode, Panagrellus redivivus.", "content": "1. Tissue levels of guanosine 3',5'-cyclic monophosphate (c-GMP) were determined by radioimmunoassay in mixed-age populations of the free living nematode Panagrellus redivivus. 2. Cyclic-GMP was identified by chromatography (ion exchange and thin-layer) and by enzymatic degradation.", "contents": "Determination of guanosine 3',5'-cyclic-monophosphate in tissues of the free living nematode, Panagrellus redivivus. 1. Tissue levels of guanosine 3',5'-cyclic monophosphate (c-GMP) were determined by radioimmunoassay in mixed-age populations of the free living nematode Panagrellus redivivus. 2. Cyclic-GMP was identified by chromatography (ion exchange and thin-layer) and by enzymatic degradation."}
{"id": "PMID:233800", "title": "Characterization of mevalonate-activating enzymes in the neonatal chick liver.", "content": "1. The 5-phosphomevalonate (MVAP) and 5-pyrophosphomevalonate (MVAPP) formation by cell-free extracts from 7-10 days chick liver shows an absolute nucleotide requirement, ATP being the most effective phosphate donor, though ITP and UTP can be used less effectively. 2. Mn2+ is a better activator than Mg2+ at low concentrations (0.1-5.0 mM). At higher concentrations (10.0 mM) Mn2+ produces a clear decrease in the MVAP formation, whereas the maximum MVAPP formation occurs in the presence of 10.0 mM Mg2+. 3. Mevalonate-activating enzymes maintain their activities for 48 hr at 4 degrees C and 24 hr at 37 degrees C. No MVAP is formed when the extracts are heated to 65 degrees C for 10 min. 4. Unlike other vertebrate mevalonate and phosphomevalonate kinases, these enzymes from chick liver are not activated by -SH group protectors as dithiothreitol, reduced glutathione, cysteine or beta-mercaptoethanol. However, the enzymes are found to be sensitive to thiol binding reagents p-hydroxymercuribenzoate and 5,5'-dithiobis-(2-nitrobenzoic acid).", "contents": "Characterization of mevalonate-activating enzymes in the neonatal chick liver. 1. The 5-phosphomevalonate (MVAP) and 5-pyrophosphomevalonate (MVAPP) formation by cell-free extracts from 7-10 days chick liver shows an absolute nucleotide requirement, ATP being the most effective phosphate donor, though ITP and UTP can be used less effectively. 2. Mn2+ is a better activator than Mg2+ at low concentrations (0.1-5.0 mM). At higher concentrations (10.0 mM) Mn2+ produces a clear decrease in the MVAP formation, whereas the maximum MVAPP formation occurs in the presence of 10.0 mM Mg2+. 3. Mevalonate-activating enzymes maintain their activities for 48 hr at 4 degrees C and 24 hr at 37 degrees C. No MVAP is formed when the extracts are heated to 65 degrees C for 10 min. 4. Unlike other vertebrate mevalonate and phosphomevalonate kinases, these enzymes from chick liver are not activated by -SH group protectors as dithiothreitol, reduced glutathione, cysteine or beta-mercaptoethanol. However, the enzymes are found to be sensitive to thiol binding reagents p-hydroxymercuribenzoate and 5,5'-dithiobis-(2-nitrobenzoic acid)."}
{"id": "PMID:233801", "title": "Enzymes involved in adenine nucleotide metabolism of developing chick embryo liver.", "content": "1. This paper describes the changes in the activity of adenylate deaminase, adenylate and inosinate phosphatase, and adenosine deaminase in the developing chick embryo liver. 2. The adenylate and inosinate phosphatase and adenosine deaminase activity appears considerably higher in chick embryo liver with respect to other chick embryo tissues previously examined. 3. During development the control exerted by ATP on AMP breakdown undergoes variations. Consequently, in the first period of incubation AMP is degraded by the direct pathway (AMP-IMP) and in the last period of incubation by the indirect pathway (AMP-adenosine). In the intermediate period (from the 12th to the 15th day of incubation) both pathways may be followed. 4. The ability to synthesize purine nucleotides through \"salvage pathway\" seems to be acquired by embryonic liver at least at the 15th day.", "contents": "Enzymes involved in adenine nucleotide metabolism of developing chick embryo liver. 1. This paper describes the changes in the activity of adenylate deaminase, adenylate and inosinate phosphatase, and adenosine deaminase in the developing chick embryo liver. 2. The adenylate and inosinate phosphatase and adenosine deaminase activity appears considerably higher in chick embryo liver with respect to other chick embryo tissues previously examined. 3. During development the control exerted by ATP on AMP breakdown undergoes variations. Consequently, in the first period of incubation AMP is degraded by the direct pathway (AMP-IMP) and in the last period of incubation by the indirect pathway (AMP-adenosine). In the intermediate period (from the 12th to the 15th day of incubation) both pathways may be followed. 4. The ability to synthesize purine nucleotides through \"salvage pathway\" seems to be acquired by embryonic liver at least at the 15th day."}
{"id": "PMID:233802", "title": "Relationship between essential fatty acid requirements of aquatic animals and the capacity for bioconversion of linolenic acid to highly unsaturated fatty acids.", "content": "1. [1-14C]linolenic acid was injected into the rainbow trout, Salmo gairdnerii, ayu, Plecoglossus altivelis, eel, Anguilla japonica, red sea bream, Chrysophrys major, rockfish, Sebastiscus marmoratus, globefish, Fugu rubripes rubripes and prawn, Penaeus japonicus (molting stage D\"1-D2), and the bioconversion of linolenic acid (18:3 omega 3) to highly unsaturated fatty acids such as eicosapentaenoic (20:5 omega 3) and docosahexaenoic (22:6 omega 3) acids was investigated. 2. Linolenic acid was converted to 20:5 omega 3 and 22:6 omega 3 intensively in the rainbow trout, moderately in the ayu, eel and prawn, but slightly in the red sea bream, rockfish and globefish. 3. These results were discussed in relation to the essential fatty acid requirements of the aquatic animals.", "contents": "Relationship between essential fatty acid requirements of aquatic animals and the capacity for bioconversion of linolenic acid to highly unsaturated fatty acids. 1. [1-14C]linolenic acid was injected into the rainbow trout, Salmo gairdnerii, ayu, Plecoglossus altivelis, eel, Anguilla japonica, red sea bream, Chrysophrys major, rockfish, Sebastiscus marmoratus, globefish, Fugu rubripes rubripes and prawn, Penaeus japonicus (molting stage D\"1-D2), and the bioconversion of linolenic acid (18:3 omega 3) to highly unsaturated fatty acids such as eicosapentaenoic (20:5 omega 3) and docosahexaenoic (22:6 omega 3) acids was investigated. 2. Linolenic acid was converted to 20:5 omega 3 and 22:6 omega 3 intensively in the rainbow trout, moderately in the ayu, eel and prawn, but slightly in the red sea bream, rockfish and globefish. 3. These results were discussed in relation to the essential fatty acid requirements of the aquatic animals."}
{"id": "PMID:233803", "title": "Isolation and characterization of a larval lipoprotein from the hemolymph of Manduca sexta.", "content": "1. The larval high density lipoprotein (HDL) from the hemolymph of Manduca sexta, isolated by density gradient centrifugation, contains 61% protein, 37% lipid and 2% carbohydrate. 2. The molecular weight of HDL is 6 x 10(5), with two apoproteins of 2.85 x 10(5) and 8.1 x 10(4) daltons. 3. The large apoprotein is destroyed by trypsin treatment of the particle, while the small one is not. 4. Calculations based upon size and composition show that this particle is very different in structure from mammalian lipoproteins. It is proposed that a portion of the apoprotein occupies the central core region.", "contents": "Isolation and characterization of a larval lipoprotein from the hemolymph of Manduca sexta. 1. The larval high density lipoprotein (HDL) from the hemolymph of Manduca sexta, isolated by density gradient centrifugation, contains 61% protein, 37% lipid and 2% carbohydrate. 2. The molecular weight of HDL is 6 x 10(5), with two apoproteins of 2.85 x 10(5) and 8.1 x 10(4) daltons. 3. The large apoprotein is destroyed by trypsin treatment of the particle, while the small one is not. 4. Calculations based upon size and composition show that this particle is very different in structure from mammalian lipoproteins. It is proposed that a portion of the apoprotein occupies the central core region."}
{"id": "PMID:233804", "title": "Red cell uridine monophosphate kinase: a comparative study in various vertebrate species.", "content": "1. Starch gel electrophoretic patterns and activity of red cell UMP-kinase were compared in different species of vertebrates. 2. A characteristic electrophoretic pattern for each species of animal studied was found. 3. The mammals differed markedly from the rest of the vertebrate compared in having a faster electrophoretic migration. 4. Significant species differences in total UMPkinase activity could be observed.", "contents": "Red cell uridine monophosphate kinase: a comparative study in various vertebrate species. 1. Starch gel electrophoretic patterns and activity of red cell UMP-kinase were compared in different species of vertebrates. 2. A characteristic electrophoretic pattern for each species of animal studied was found. 3. The mammals differed markedly from the rest of the vertebrate compared in having a faster electrophoretic migration. 4. Significant species differences in total UMPkinase activity could be observed."}
{"id": "PMID:233808", "title": "Subcellular localization of glucose-6-phosphatase in animal tissues.", "content": "1. Glucose-6-phosphatase (EC 3.1.3.9 D-glucose-6-phosphate phosphohydrolase) was found to be localized mainly in the endoplasmic reticulum (microsomal fraction) of all species of vertebrate liver tissue examined. 2. Hepatopancreas tissue from gastropod molluscs was found to be unique in showing the localization of glucose-6-phosphatase in the cytosol (soluble fraction).", "contents": "Subcellular localization of glucose-6-phosphatase in animal tissues. 1. Glucose-6-phosphatase (EC 3.1.3.9 D-glucose-6-phosphate phosphohydrolase) was found to be localized mainly in the endoplasmic reticulum (microsomal fraction) of all species of vertebrate liver tissue examined. 2. Hepatopancreas tissue from gastropod molluscs was found to be unique in showing the localization of glucose-6-phosphatase in the cytosol (soluble fraction)."}
{"id": "PMID:233809", "title": "Mechanism of L-serine oxidation in Entamoeba histolytica.", "content": "1. The enzymatic mechanism of oxygen uptake elicited by L-serine in axenically cultivated trophozoites of Entamoeba histolytica was investigated. 2. Of 22 amino acids examined, only L-serine stimulated oxygen consumption by intact and disrupted amoebae. 3. Pyruvate, a product of serine metabolism, also stimulated oxygen consumption in the amoebae. 4. Characterization of the oxygen uptake elicited by both L-serine and pyruvate, and analysis of the products of L-serine metabolism indicate that the amino acid is first converted to pyruvate. 5. L-Serine dehydratase, which catalyzes the deamination of serine to pyruvate, was detected primarily in the soluble fraction of the amoebae. D-Serine potently inhibited the enzyme, as well as oxygen uptake in the presence of L-serine but not in the presence of pyruvate. 6. The pyruvate formed is oxidized, at least in part, by a novel pyruvate oxidase involving the uptake of molecular oxygen.", "contents": "Mechanism of L-serine oxidation in Entamoeba histolytica. 1. The enzymatic mechanism of oxygen uptake elicited by L-serine in axenically cultivated trophozoites of Entamoeba histolytica was investigated. 2. Of 22 amino acids examined, only L-serine stimulated oxygen consumption by intact and disrupted amoebae. 3. Pyruvate, a product of serine metabolism, also stimulated oxygen consumption in the amoebae. 4. Characterization of the oxygen uptake elicited by both L-serine and pyruvate, and analysis of the products of L-serine metabolism indicate that the amino acid is first converted to pyruvate. 5. L-Serine dehydratase, which catalyzes the deamination of serine to pyruvate, was detected primarily in the soluble fraction of the amoebae. D-Serine potently inhibited the enzyme, as well as oxygen uptake in the presence of L-serine but not in the presence of pyruvate. 6. The pyruvate formed is oxidized, at least in part, by a novel pyruvate oxidase involving the uptake of molecular oxygen."}
{"id": "PMID:233810", "title": "Levels of true thymidine kinase and nucleoside phosphotransferase in two strains of Tetrahymena pyriformis under different growth conditions.", "content": "Activities of typical thymidine kinase and nucleoside phosphotransferase are both present in logarithmically growing tetrahymena pyriformis, GL-1 and ST strains, contrary to previous reports. 2. Activities of thymidine kinase and nucleoside phosphotransferase are also found in both GL-1 and ST strains grown in the defined medium, PPL medium and Neff's medium. 3. The specific activities of both enzymes are very much influenced by the growth state. Both the specific activities of thymidine kinase and nucleoside phosphotransferase decrease steadily from the start of the experiments when the cell numbers were about 2-3 x 10(4) cells/ml in the PPL medium, while in the Neff's medium, the specific activities of thymidine kinase increase up to when the cell numbers reached 3-5 x 10(5) cells/ml and then decreased, but the specific activities of nucleoside phosphotransferase continuously decreased when the cell concentrations were 2-6 x 10(4) cells/ml. 4. In the PPL medium, the final cell numbers reached are about 6.5 x 10(5) cells/ml, while in the Neff's medium, the cell numbers increase further (to about 2 x 10(6) cells/ml). 5. No striking difference in activities of thymidine kinase and nucleoside phosphotransferase was observed when the cells were transferred from the defined medium to the Neff's medium, contrary to that reported by others for the activity of thymidylate synthetase.", "contents": "Levels of true thymidine kinase and nucleoside phosphotransferase in two strains of Tetrahymena pyriformis under different growth conditions. Activities of typical thymidine kinase and nucleoside phosphotransferase are both present in logarithmically growing tetrahymena pyriformis, GL-1 and ST strains, contrary to previous reports. 2. Activities of thymidine kinase and nucleoside phosphotransferase are also found in both GL-1 and ST strains grown in the defined medium, PPL medium and Neff's medium. 3. The specific activities of both enzymes are very much influenced by the growth state. Both the specific activities of thymidine kinase and nucleoside phosphotransferase decrease steadily from the start of the experiments when the cell numbers were about 2-3 x 10(4) cells/ml in the PPL medium, while in the Neff's medium, the specific activities of thymidine kinase increase up to when the cell numbers reached 3-5 x 10(5) cells/ml and then decreased, but the specific activities of nucleoside phosphotransferase continuously decreased when the cell concentrations were 2-6 x 10(4) cells/ml. 4. In the PPL medium, the final cell numbers reached are about 6.5 x 10(5) cells/ml, while in the Neff's medium, the cell numbers increase further (to about 2 x 10(6) cells/ml). 5. No striking difference in activities of thymidine kinase and nucleoside phosphotransferase was observed when the cells were transferred from the defined medium to the Neff's medium, contrary to that reported by others for the activity of thymidylate synthetase."}
{"id": "PMID:233811", "title": "The biosynthesis of nicotinamide adenine dinucleotide during early stages of frog embryonic development of haploid and diploid embryos.", "content": "1. Concentration of NAD during embryonic development of haploid and diploid embryos of frog was followed. NAD content in haploid embryonic forms is twice that in diploid embryos. 2. The variation of the NMN adenylyltransferase activity in the oocytes and during the first states of embryonic development as surveyed in the nuclear soluble fraction and the nuclear insoluble fraction (chromatin). 3. The enzyme activity in the soluble fraction is low during embryonic development and shows higher values in haploid embryos. 4. In the nonfertilized mature oocytes, the NMN adenylyltransferase activity is sixfold higher in the insoluble chromatin fraction than in the soluble fraction. 5. The evolution of the NMN adenylyltransferase in the insoluble chromatin fraction also shows higher values in haploid embryos, as compared with diploid forms.", "contents": "The biosynthesis of nicotinamide adenine dinucleotide during early stages of frog embryonic development of haploid and diploid embryos. 1. Concentration of NAD during embryonic development of haploid and diploid embryos of frog was followed. NAD content in haploid embryonic forms is twice that in diploid embryos. 2. The variation of the NMN adenylyltransferase activity in the oocytes and during the first states of embryonic development as surveyed in the nuclear soluble fraction and the nuclear insoluble fraction (chromatin). 3. The enzyme activity in the soluble fraction is low during embryonic development and shows higher values in haploid embryos. 4. In the nonfertilized mature oocytes, the NMN adenylyltransferase activity is sixfold higher in the insoluble chromatin fraction than in the soluble fraction. 5. The evolution of the NMN adenylyltransferase in the insoluble chromatin fraction also shows higher values in haploid embryos, as compared with diploid forms."}
{"id": "PMID:233812", "title": "Acid glycohydrolase in Chinese hamster (Cricetulus griseus) with spontaneous diabetes--V. Subcellular distribution in the kidney.", "content": "1. Seven renal glycohydrolases were measured in four subcellular fractions prepared from highly inbred aglycosuric (AV-line) and glycosuric (XA-line) Chinese hamsters. 2. alpha-D-galactosidase and beta-D-galactosidase were highest in the nuclear (N) and supernatant (S) fractions; both fractions showed reduced activities in the XA animals. 3. alpha-D-mannosidase was chiefly a particulate enzyme and its decrease in XA animals was evident in N, lysosomal-mitochondrial (LM) and mitochondrial-microsomal (MM) fractions. 4. No significant difference in N-acetyl-beta-D-glucosaminidase was found in any of these subcellular fractions between AV and XA animals. 5. Although total alpha-L-fucosidase and beta-D-fucosidase levels were similar in AV and XA kidneys, a difference was observed in the S fraction. 6. beta-D-glucuronidase was virtually absent in N and LM fractions and the S fraction of AV kidneys showed higher activity than the XAs.", "contents": "Acid glycohydrolase in Chinese hamster (Cricetulus griseus) with spontaneous diabetes--V. Subcellular distribution in the kidney. 1. Seven renal glycohydrolases were measured in four subcellular fractions prepared from highly inbred aglycosuric (AV-line) and glycosuric (XA-line) Chinese hamsters. 2. alpha-D-galactosidase and beta-D-galactosidase were highest in the nuclear (N) and supernatant (S) fractions; both fractions showed reduced activities in the XA animals. 3. alpha-D-mannosidase was chiefly a particulate enzyme and its decrease in XA animals was evident in N, lysosomal-mitochondrial (LM) and mitochondrial-microsomal (MM) fractions. 4. No significant difference in N-acetyl-beta-D-glucosaminidase was found in any of these subcellular fractions between AV and XA animals. 5. Although total alpha-L-fucosidase and beta-D-fucosidase levels were similar in AV and XA kidneys, a difference was observed in the S fraction. 6. beta-D-glucuronidase was virtually absent in N and LM fractions and the S fraction of AV kidneys showed higher activity than the XAs."}
{"id": "PMID:233814", "title": "Combination chemotherapy including high dose methotrexate and radiotherapy, in the treatment of small cell carcinoma of the lung.", "content": "Twenty-nine (88%) of thirty-three patients who were treated with multiple drug chemotherapy, including high dose methotrexate, and radiotherapy for small cell carcinoma of the lung showed significant improvement in their clinical condition and quality of life. Treatment was well tolerated and toxicity acceptable. Cerebral metastases were not detected in any patient on presentation and only developed in three patients (9%). Little information exists regarding the use of high dose methotrexate in small cell carcinoma of the lung. There is no evidence, on the data available, that high dose methotrexate is any more effective than conventional doses.", "contents": "Combination chemotherapy including high dose methotrexate and radiotherapy, in the treatment of small cell carcinoma of the lung. Twenty-nine (88%) of thirty-three patients who were treated with multiple drug chemotherapy, including high dose methotrexate, and radiotherapy for small cell carcinoma of the lung showed significant improvement in their clinical condition and quality of life. Treatment was well tolerated and toxicity acceptable. Cerebral metastases were not detected in any patient on presentation and only developed in three patients (9%). Little information exists regarding the use of high dose methotrexate in small cell carcinoma of the lung. There is no evidence, on the data available, that high dose methotrexate is any more effective than conventional doses."}
{"id": "PMID:233815", "title": "Biological effects of chrysotile after SO2 sorption. II. Effects on alveolar macrophages and red blood cells.", "content": "An experimental study has been carried out using different biological and biochemical in vivo and in vitro tests for assessing the toxicity of natural UICC (A) chrysotile and SO2-sorbed UICC (A) chrysotile and for detecting a possible synergistic effect. For in vivo studies, rabbits received an intratracheal injection of chrysotile fibers suspended in physiological saline (PS). The control group received only PS; all animals were sacrificed after 68 hr. The alveolar free cells were harvested by pulmonary lavage. The results have shown that chrysotile induces a decrease in the free cell population but there was no significant difference in the number of viable cells or in the nature of cells harvested between the two chrysotile groups. Enzymatic activities of the alveolar macrophages from animals injected with SO2-sorbed chrysotile showed a significant increase of the enzymes LDH and acid phosphatases. The LDH increase could be related to the affinity of the enzyme regarding some chemical forms of SO2. In vitro studies using alveolar macrophages harvested by pulmonary lavage have shown no differences between the two chrysotile groups when cell viability and enzyme release were studied. The toxic effect was due to chrysotile fibers (decrease of 38% in cell viability and increase in cellular enzyme release when compared with control). When rabbit red blood cells were used, both natural and SO2 chrysotile fibers showed the same hemolytic activity. The failure to detect high differences between the two chrysotile groups may be related to the chemical form of sorbed SO2.", "contents": "Biological effects of chrysotile after SO2 sorption. II. Effects on alveolar macrophages and red blood cells. An experimental study has been carried out using different biological and biochemical in vivo and in vitro tests for assessing the toxicity of natural UICC (A) chrysotile and SO2-sorbed UICC (A) chrysotile and for detecting a possible synergistic effect. For in vivo studies, rabbits received an intratracheal injection of chrysotile fibers suspended in physiological saline (PS). The control group received only PS; all animals were sacrificed after 68 hr. The alveolar free cells were harvested by pulmonary lavage. The results have shown that chrysotile induces a decrease in the free cell population but there was no significant difference in the number of viable cells or in the nature of cells harvested between the two chrysotile groups. Enzymatic activities of the alveolar macrophages from animals injected with SO2-sorbed chrysotile showed a significant increase of the enzymes LDH and acid phosphatases. The LDH increase could be related to the affinity of the enzyme regarding some chemical forms of SO2. In vitro studies using alveolar macrophages harvested by pulmonary lavage have shown no differences between the two chrysotile groups when cell viability and enzyme release were studied. The toxic effect was due to chrysotile fibers (decrease of 38% in cell viability and increase in cellular enzyme release when compared with control). When rabbit red blood cells were used, both natural and SO2 chrysotile fibers showed the same hemolytic activity. The failure to detect high differences between the two chrysotile groups may be related to the chemical form of sorbed SO2."}
{"id": "PMID:233816", "title": "Effects of asbestos on epithelioid cell lines.", "content": "The in vitro effects of asbestos fibers on the growth and viability of CHO cells, an epithelioid cell line derived from Chinese hamster ovary, and on K-22 cells, an epithelial cell line derived from rat liver, have been studied. Relatively low concentrations of asbestos (10 micrograms/ml) were quite cytotoxic to both cell types. A sample of chrysotile asbestos was more toxic than samples of crocidolite or amosite. The toxic factor could not be extracted from the asbestos and toxicity occurred only if there was physical contact between the fibers and the cells. Although the phorbol ester class of tumor promoters induces the synthesis of plasminogen activator in various cell cultures, asbestos did not induce this protease in epithelioid or fibroblast cell cultures. The results obtained are compared to previous in vitro results obtained with fibroblast or macrophage cultures and are discussed in terms of their possible relevance to asbestos-induced fibrosis and tumorigenesis.", "contents": "Effects of asbestos on epithelioid cell lines. The in vitro effects of asbestos fibers on the growth and viability of CHO cells, an epithelioid cell line derived from Chinese hamster ovary, and on K-22 cells, an epithelial cell line derived from rat liver, have been studied. Relatively low concentrations of asbestos (10 micrograms/ml) were quite cytotoxic to both cell types. A sample of chrysotile asbestos was more toxic than samples of crocidolite or amosite. The toxic factor could not be extracted from the asbestos and toxicity occurred only if there was physical contact between the fibers and the cells. Although the phorbol ester class of tumor promoters induces the synthesis of plasminogen activator in various cell cultures, asbestos did not induce this protease in epithelioid or fibroblast cell cultures. The results obtained are compared to previous in vitro results obtained with fibroblast or macrophage cultures and are discussed in terms of their possible relevance to asbestos-induced fibrosis and tumorigenesis."}
{"id": "PMID:233817", "title": "Low level lead and inhibition of erythrocyte pyrimidine nucleotidase.", "content": "Pyrimidine 5'-nucleotidase (P5N, EC 3.1.3.5) appears to be a sensitive index of exposure to low level lead. In 21 children 2 to 5 years old with blood leads of 7 to 80 micrograms/dl there was a negative linear correlation of blood lead and red cell P5N: r = -0.60 (P less than 0.01), Y = -0.11X + 12.3. In rats, the enzyme assay was quantitatively similar to that of the human. A treatment group of 12 rats received lead acetate, 36 mg/kg/day, of lead as 0.17 M lead acetate for 24 days. The blood lead of treated rats increased from the control value of 8.3 +/- 1.3 to 36.0 +/- 0.5 on day 24; P5N decreased from 18.3 +/- 0.8 units to 9.0 +/- 1.0 and was below control values at a blood lead of 25. There was a significant negative linear correlation of blood lead and P5N: r = -0.85; n = 17; P less than 0.001; Y = 0.34X + 20.9 that was independent of the correlationship with the reticulocytes. At these levels of blood lead and P5N there was no significant change in the hexokinase, hemoglobin or red cell count and no evidence of stippling.", "contents": "Low level lead and inhibition of erythrocyte pyrimidine nucleotidase. Pyrimidine 5'-nucleotidase (P5N, EC 3.1.3.5) appears to be a sensitive index of exposure to low level lead. In 21 children 2 to 5 years old with blood leads of 7 to 80 micrograms/dl there was a negative linear correlation of blood lead and red cell P5N: r = -0.60 (P less than 0.01), Y = -0.11X + 12.3. In rats, the enzyme assay was quantitatively similar to that of the human. A treatment group of 12 rats received lead acetate, 36 mg/kg/day, of lead as 0.17 M lead acetate for 24 days. The blood lead of treated rats increased from the control value of 8.3 +/- 1.3 to 36.0 +/- 0.5 on day 24; P5N decreased from 18.3 +/- 0.8 units to 9.0 +/- 1.0 and was below control values at a blood lead of 25. There was a significant negative linear correlation of blood lead and P5N: r = -0.85; n = 17; P less than 0.001; Y = 0.34X + 20.9 that was independent of the correlationship with the reticulocytes. At these levels of blood lead and P5N there was no significant change in the hexokinase, hemoglobin or red cell count and no evidence of stippling."}
{"id": "PMID:233818", "title": "Mesothelioma after crocidolite exposure during gas mask manufacture.", "content": "Of 199 persons employed in the manufacture and handling of Canadian military gas mask canisters containing pure crocidolite, 1939 to 1942, by the end of 1975, 56 had died, 120 were still alive, and 23 could not be traced. Nine (16%) of the deaths were probably due to malignant mesothelioma, six involving the peritoneum. The risk of mesothelioma after crocidolite exposure appears to be many times greater than that after chrysotile.", "contents": "Mesothelioma after crocidolite exposure during gas mask manufacture. Of 199 persons employed in the manufacture and handling of Canadian military gas mask canisters containing pure crocidolite, 1939 to 1942, by the end of 1975, 56 had died, 120 were still alive, and 23 could not be traced. Nine (16%) of the deaths were probably due to malignant mesothelioma, six involving the peritoneum. The risk of mesothelioma after crocidolite exposure appears to be many times greater than that after chrysotile."}
{"id": "PMID:233819", "title": "Kinetics of the potential-sensitive extrinsic probe oxonol VI in beef heart submitochondrial particles.", "content": "The interaction of the potential-sensitive extrinsic probe oxonol VI with beef heart submitochondrial particles has been investigated under time resolved and equilibrium conditions. The time course of the probe absorption spectrum red shift induced by ATP or NADH injection into a suspension of submitochondrial particles in a dye solution is biphasic, consisting of a faster process described by a second-order rate law with k2 approximately 3 x 10(5) M-1 sec-1. For the ATP pulse experiments, the slower process follows first-order kinetics with k1 approximately 0.3 sec-1. In oxygen pulse experiments to an anaerobic dye-particle system, the slower process is not significantly developed due to rapid depletion of the oxygen, but the faster process follows second-order kinetics with the same rate of the oxygen, but the faster process follows second-order kinetics with the same rate constant as for the ATP and NADH cases. Evidence for permeation of the submitochondrial particle membrane by oxonol VI has been obtained; the slower process is interpretable as describing the permeation of the membrane bilayer. The results of the time-resolved work are consistent with a mechanism involving a redistribution of the dye from the bulk phase to the particle membrane. The value of the second-order rate constant for passive binding of the dye to submitochondrial particles is not compatible with a mechanism proposed to explain the microsecond probe response times in bilayer and excitable membrane experiments nor are such rapid signals observed in the oxonol VI-submitochondrial particle system.", "contents": "Kinetics of the potential-sensitive extrinsic probe oxonol VI in beef heart submitochondrial particles. The interaction of the potential-sensitive extrinsic probe oxonol VI with beef heart submitochondrial particles has been investigated under time resolved and equilibrium conditions. The time course of the probe absorption spectrum red shift induced by ATP or NADH injection into a suspension of submitochondrial particles in a dye solution is biphasic, consisting of a faster process described by a second-order rate law with k2 approximately 3 x 10(5) M-1 sec-1. For the ATP pulse experiments, the slower process follows first-order kinetics with k1 approximately 0.3 sec-1. In oxygen pulse experiments to an anaerobic dye-particle system, the slower process is not significantly developed due to rapid depletion of the oxygen, but the faster process follows second-order kinetics with the same rate of the oxygen, but the faster process follows second-order kinetics with the same rate constant as for the ATP and NADH cases. Evidence for permeation of the submitochondrial particle membrane by oxonol VI has been obtained; the slower process is interpretable as describing the permeation of the membrane bilayer. The results of the time-resolved work are consistent with a mechanism involving a redistribution of the dye from the bulk phase to the particle membrane. The value of the second-order rate constant for passive binding of the dye to submitochondrial particles is not compatible with a mechanism proposed to explain the microsecond probe response times in bilayer and excitable membrane experiments nor are such rapid signals observed in the oxonol VI-submitochondrial particle system."}
{"id": "PMID:233820", "title": "Ontogeny and effect of vitamin D deprivation on rat serum 25-hydroxyvitamin D binding protein.", "content": "Specific serum binding of 25-hydroxy-cholecalciferol (25-OHD3) was measured by saturation analysis in rats of various ages, and during vitamin D deprivation. The serum binding capacity for 25-OHD3 was observed to increase until age 6-8 weeks, then decline and remain stable thereafter at 3.7 x 10(-6) M. The 25-hydroxyvitamin D (25-OHD) concentration decreased in serum from rats fed vitamin D-free diet (t1/2 = 7 days). Rats fed 2 IU of vitamin D3/g of diet maintained stable serum levels of 25-OHD at 10-12 ng/ml. Serum binding capacity and affinity for 25-OHD3 was not affected by vitamin D deprivation or hypocalcemia. In addition, the binding affinity did not differ as a function of age (Kd = 3.3 x 10(-9) M). Since normal serum concentrations of 25-OHD in the rat are 2-5 x 10(-8) M, only 1-2% of the serum binding sites for this sterol are occupied under physiological conditions.", "contents": "Ontogeny and effect of vitamin D deprivation on rat serum 25-hydroxyvitamin D binding protein. Specific serum binding of 25-hydroxy-cholecalciferol (25-OHD3) was measured by saturation analysis in rats of various ages, and during vitamin D deprivation. The serum binding capacity for 25-OHD3 was observed to increase until age 6-8 weeks, then decline and remain stable thereafter at 3.7 x 10(-6) M. The 25-hydroxyvitamin D (25-OHD) concentration decreased in serum from rats fed vitamin D-free diet (t1/2 = 7 days). Rats fed 2 IU of vitamin D3/g of diet maintained stable serum levels of 25-OHD at 10-12 ng/ml. Serum binding capacity and affinity for 25-OHD3 was not affected by vitamin D deprivation or hypocalcemia. In addition, the binding affinity did not differ as a function of age (Kd = 3.3 x 10(-9) M). Since normal serum concentrations of 25-OHD in the rat are 2-5 x 10(-8) M, only 1-2% of the serum binding sites for this sterol are occupied under physiological conditions."}
{"id": "PMID:233821", "title": "Evidence for a role of alpha-adrenergic mechanisms in regulation of episodic growth hormone secretion in the rat.", "content": "The role of catecholamines in regulation of episodic GH secretion was investigated in the male rat. Administration of alpha-methyl-p-tyrosine (alpha-MT; 250 mg/kg ip) caused significant suppression of GH bursts and resulted in marked elevation of plasma PRL. Intravenous administration of apomorphine (.03 and .1 mg/kg) had no effect on decreased GH levels, whereas clonidine (150 micrograms/kg) restored GH secretion. Apomorphine significantly reduced PRL levels in alpha-MT-treated rats whereas, clonidine resulted in a further increase in PRL.", "contents": "Evidence for a role of alpha-adrenergic mechanisms in regulation of episodic growth hormone secretion in the rat. The role of catecholamines in regulation of episodic GH secretion was investigated in the male rat. Administration of alpha-methyl-p-tyrosine (alpha-MT; 250 mg/kg ip) caused significant suppression of GH bursts and resulted in marked elevation of plasma PRL. Intravenous administration of apomorphine (.03 and .1 mg/kg) had no effect on decreased GH levels, whereas clonidine (150 micrograms/kg) restored GH secretion. Apomorphine significantly reduced PRL levels in alpha-MT-treated rats whereas, clonidine resulted in a further increase in PRL."}
{"id": "PMID:233822", "title": "Cultured thyroid cell adenosine 3',5'-cyclic monophosphate response to thyrotropin: loss and restoration of sensitivity to iodide inhibition.", "content": "Unlike in all other thyroid preparations, exposure of dog thyroid cells in long-term monolayer culture to iodide (10(-7) to 10(-3) M for up to 19 h did not blunt the subsequent adenosine 3', 5'-cyclic monophosphate (cAMP) response to thyrotropin (TSH) stimulation. This lack of effect of iodide was observed even when confluent thyroid cells were \"follicularized\" by the action of TSH in the culture medium. Preincubation of these cells in thyroxine (T4) and triiodothyronine (T3) was similarly without effect on the subsequent cAMP response to TSH. Study of thyroid cells during the early phase of primary culture demonstrated that inhibition by iodide (10(-4) M) of the cAMP response to TSH occurred after 7 h but was lost after 48 h of cell culture. This inhibitory effect of iodide was prevented by the inclusion of methimazole in the preincubation medium. As with iodide-insensitive cells, T4 and T3 were without effect on the cAMP response to TSH in iodide-sensitive thyroid cells. Exposure of iodide-insensitive thyroid cells to iodide-containing medium obtained after 2 h of incubation with dog thyroid slices, as well as to medium enriched with the 100,000 g supernatant fraction of homogenates prepared from these thyroid slices, did not restore the inhibitory action of iodide. However, iodide-sensitivity of the cAMP response to TSH was restored by preincubation of iodide-insensitive cells in 10(-4) M iodide plus an H2O2-generating system (glucose-glucose oxidase). These data suggest that T4 and T3 are not organic iodine inhibitors of the thyroid cAMP response to TSH. In addition, they provide evidence against the existence of a soluble, freely diffusible, organic iodine inhibitor of thyroid adenylate cyclase. The loss of sensitivity to iodide inhibition of adenylate cyclase that occurs in thyroid cells shortly after initiation of primary culture appears to be related to a defect in the cellular organification mechanism, possibly the H2O2-generating system.", "contents": "Cultured thyroid cell adenosine 3',5'-cyclic monophosphate response to thyrotropin: loss and restoration of sensitivity to iodide inhibition. Unlike in all other thyroid preparations, exposure of dog thyroid cells in long-term monolayer culture to iodide (10(-7) to 10(-3) M for up to 19 h did not blunt the subsequent adenosine 3', 5'-cyclic monophosphate (cAMP) response to thyrotropin (TSH) stimulation. This lack of effect of iodide was observed even when confluent thyroid cells were \"follicularized\" by the action of TSH in the culture medium. Preincubation of these cells in thyroxine (T4) and triiodothyronine (T3) was similarly without effect on the subsequent cAMP response to TSH. Study of thyroid cells during the early phase of primary culture demonstrated that inhibition by iodide (10(-4) M) of the cAMP response to TSH occurred after 7 h but was lost after 48 h of cell culture. This inhibitory effect of iodide was prevented by the inclusion of methimazole in the preincubation medium. As with iodide-insensitive cells, T4 and T3 were without effect on the cAMP response to TSH in iodide-sensitive thyroid cells. Exposure of iodide-insensitive thyroid cells to iodide-containing medium obtained after 2 h of incubation with dog thyroid slices, as well as to medium enriched with the 100,000 g supernatant fraction of homogenates prepared from these thyroid slices, did not restore the inhibitory action of iodide. However, iodide-sensitivity of the cAMP response to TSH was restored by preincubation of iodide-insensitive cells in 10(-4) M iodide plus an H2O2-generating system (glucose-glucose oxidase). These data suggest that T4 and T3 are not organic iodine inhibitors of the thyroid cAMP response to TSH. In addition, they provide evidence against the existence of a soluble, freely diffusible, organic iodine inhibitor of thyroid adenylate cyclase. The loss of sensitivity to iodide inhibition of adenylate cyclase that occurs in thyroid cells shortly after initiation of primary culture appears to be related to a defect in the cellular organification mechanism, possibly the H2O2-generating system."}
{"id": "PMID:233823", "title": "Influence of dietary vitamin D3 on the circulating concentration of its active metabolites in the chick and rat.", "content": "Plasma concentrations of 25-hydroxyvitamin D3 (25-OHD3) and 1 alpha,25-dihydroxyvitamin D3 (1 alpha, 25-(OH)2D3) in growing chicks and weanling rats were measured by a new radioreceptor assay to determine the effects of varying dietary levels of vitamin D3. The plasma concentration of 25-OHD3 fell from 14.1 ng/ml in 1-day-old chicks to undetectable levels after 3 weeks on a rachitogenic diet. Circulating 1 alpha,25-(OH)2D3 hormone also decreased from 8.9 ng/100 ml to undetectable levels at 3 weeks in these chicks. Chicks receiving an optimal supplement of vitamin D3 (1.4 IU/g diet) for three to four weeks had plasma 25-OHD3 and 1 alpha,25-(OH)2D3 levels of 21-35 ng/ml and 5.1-7.5 ng/100 ml, respectively. Nutritional supplementation with a 50-fold excess of vitamin D3 (70 IU/g diet) elicited a substantial increase in plasma 25-OHD3 to 87-130 ng/ml, while plasma 1 alpha,25-(OH)2D3 was not increased. Increasing dietary calcium from 1.4 to 2.8% did not alter the circulating level of vitamin D3 metabolites in chicks fed 1.4 IU of vitamin D3/g diet. Direct measurement of the renal 25-OHD3-1 alpha-hydroxylase in vitro, showed that lowering dietary calcium or exclusion of vitamin D3 stimulated the biosynthesis of 1 alpha,25-(OH)2D3, but raising calcium did not alter the enzyme activity. It is concluded that the circulating concentration of the 1 alpha,25-(OH)2D3 hormone in the chick is unaffected by abnormally high intakes of vitamin D3 or calcium, but the renal production of the hormone increases during vitamin D3 or calcium deprivation. Additional studies in rats fed a diet supplemented with either 2 or 1000 IU of vitamin D3/g verify that the circulating concentration of 25-OHD3 is markedly increased when the dietary intake of vitamin D3 is elevated. Moreover, 1 alpha,25(OH)2D3 is not increased under these conditions, but actually falls significantly when the dietary level of vitamin D3 is raised from 2 to 1000 IU/g. These studies in both the chick and rat indicate that dietary vitamin D3 excess enhances circulating 25-OHD3, probably because the vitamin D3-25-hydroxylase enzyme is not strigently controlled. The fact that the circulating 1 alpha,25-(OH)2D3 is not concomitantly increased may reflect either decreased synthesis or increased utilization of the 1 alpha,25-(OH)2D3 sterol.", "contents": "Influence of dietary vitamin D3 on the circulating concentration of its active metabolites in the chick and rat. Plasma concentrations of 25-hydroxyvitamin D3 (25-OHD3) and 1 alpha,25-dihydroxyvitamin D3 (1 alpha, 25-(OH)2D3) in growing chicks and weanling rats were measured by a new radioreceptor assay to determine the effects of varying dietary levels of vitamin D3. The plasma concentration of 25-OHD3 fell from 14.1 ng/ml in 1-day-old chicks to undetectable levels after 3 weeks on a rachitogenic diet. Circulating 1 alpha,25-(OH)2D3 hormone also decreased from 8.9 ng/100 ml to undetectable levels at 3 weeks in these chicks. Chicks receiving an optimal supplement of vitamin D3 (1.4 IU/g diet) for three to four weeks had plasma 25-OHD3 and 1 alpha,25-(OH)2D3 levels of 21-35 ng/ml and 5.1-7.5 ng/100 ml, respectively. Nutritional supplementation with a 50-fold excess of vitamin D3 (70 IU/g diet) elicited a substantial increase in plasma 25-OHD3 to 87-130 ng/ml, while plasma 1 alpha,25-(OH)2D3 was not increased. Increasing dietary calcium from 1.4 to 2.8% did not alter the circulating level of vitamin D3 metabolites in chicks fed 1.4 IU of vitamin D3/g diet. Direct measurement of the renal 25-OHD3-1 alpha-hydroxylase in vitro, showed that lowering dietary calcium or exclusion of vitamin D3 stimulated the biosynthesis of 1 alpha,25-(OH)2D3, but raising calcium did not alter the enzyme activity. It is concluded that the circulating concentration of the 1 alpha,25-(OH)2D3 hormone in the chick is unaffected by abnormally high intakes of vitamin D3 or calcium, but the renal production of the hormone increases during vitamin D3 or calcium deprivation. Additional studies in rats fed a diet supplemented with either 2 or 1000 IU of vitamin D3/g verify that the circulating concentration of 25-OHD3 is markedly increased when the dietary intake of vitamin D3 is elevated. Moreover, 1 alpha,25(OH)2D3 is not increased under these conditions, but actually falls significantly when the dietary level of vitamin D3 is raised from 2 to 1000 IU/g. These studies in both the chick and rat indicate that dietary vitamin D3 excess enhances circulating 25-OHD3, probably because the vitamin D3-25-hydroxylase enzyme is not strigently controlled. The fact that the circulating 1 alpha,25-(OH)2D3 is not concomitantly increased may reflect either decreased synthesis or increased utilization of the 1 alpha,25-(OH)2D3 sterol."}
{"id": "PMID:233825", "title": "Effect of wheat fiber on blood lipids, fecal steroid excretion and serum iron.", "content": "Adding 36 g of wheat fiber for 3 weeks to the metabolically controlled diets of six subjects produced a significant increase in daily fecal weight from 70.8 g +/- 6.2 SEM to 217 g +/- 12.1; serum iron also fell by 21 micrograms/100 ml +/- 2.1 SEM (P less than 0.001) during the added fiber period (measured in five subjects) as did mean corpuscular volume and mean corpuscular hemoglobin. Fecal neutral steroid concentration (measured in four subjects) fell from 31 to 17.3 mg/g dry weight (P less than 0.05) but the change in neutral steroid output and in acid steroid concentration and output was not significant. No change was seen in the serum levels of cholesterol and triglyceride.", "contents": "Effect of wheat fiber on blood lipids, fecal steroid excretion and serum iron. Adding 36 g of wheat fiber for 3 weeks to the metabolically controlled diets of six subjects produced a significant increase in daily fecal weight from 70.8 g +/- 6.2 SEM to 217 g +/- 12.1; serum iron also fell by 21 micrograms/100 ml +/- 2.1 SEM (P less than 0.001) during the added fiber period (measured in five subjects) as did mean corpuscular volume and mean corpuscular hemoglobin. Fecal neutral steroid concentration (measured in four subjects) fell from 31 to 17.3 mg/g dry weight (P less than 0.05) but the change in neutral steroid output and in acid steroid concentration and output was not significant. No change was seen in the serum levels of cholesterol and triglyceride."}
{"id": "PMID:233826", "title": "Surgical management of carotid body tumor.", "content": "Carotid body tumor or chemodectoma is a slow-growing lesion; it should be diagnosed early to facilitate the technical surgical resection. When these lesions are large, the routine use of a carotid internal bypass shunt is advocated for their safe removal. With the newer vascular approaches, specifically the carotid internal bypass shunt, resection can be performed with acceptable risks. A patient with large bilateral carotid body tumors had successful resection of both these lesions.", "contents": "Surgical management of carotid body tumor. Carotid body tumor or chemodectoma is a slow-growing lesion; it should be diagnosed early to facilitate the technical surgical resection. When these lesions are large, the routine use of a carotid internal bypass shunt is advocated for their safe removal. With the newer vascular approaches, specifically the carotid internal bypass shunt, resection can be performed with acceptable risks. A patient with large bilateral carotid body tumors had successful resection of both these lesions."}
{"id": "PMID:233843", "title": "The effects of miconazole on the ultrastructure of Candida albicans.", "content": "Ultrastructural changes in Candida albicans induced by increasing concentrations of miconazole in vitro are described. Fungistatic concentrations (10(-8) to 10(-7) M) induced minimal morphologic changes at the cell periphery. At 10(-6) M cell volume increased and peroxisomes became numerous in the cell interior. The minimal fungicidal dose of 10(-5) M caused severe damage to most of the cell population and a total fungicidal dose of 10(-4) M caused total internal cellular necrosis even when cell walls remained intact. It is suggested that miconazole inhibits the peroxidative enzymes cytochrome c-peroxidase and catalase. Cell necrosis then results from peroxide accumulation.", "contents": "The effects of miconazole on the ultrastructure of Candida albicans. Ultrastructural changes in Candida albicans induced by increasing concentrations of miconazole in vitro are described. Fungistatic concentrations (10(-8) to 10(-7) M) induced minimal morphologic changes at the cell periphery. At 10(-6) M cell volume increased and peroxisomes became numerous in the cell interior. The minimal fungicidal dose of 10(-5) M caused severe damage to most of the cell population and a total fungicidal dose of 10(-4) M caused total internal cellular necrosis even when cell walls remained intact. It is suggested that miconazole inhibits the peroxidative enzymes cytochrome c-peroxidase and catalase. Cell necrosis then results from peroxide accumulation."}
{"id": "PMID:233844", "title": "Mechanism of enamel dissolution and its prevention.", "content": "In this paper the mechanism of dental enamel dissolution is discussed. Special attention is given to the anisotropic solubility behaviour (hollow tube formation) of demineralized enamel crystallites. The combined evidence strongly indicates that this peculiar dissolution behaviour is caused by dislocations. The dislocations--linear lattice defects--are present in the crystallite center and are the cause of two active dissolution sites in each crystallite. Initial as well as later stages in the caries process are discussed. Experimental evidence is presented which indicates that the active sites can be inactivated by agents like EHDP and MFP. After inactivation, acid penetration is either prevented or strongly retarded.", "contents": "Mechanism of enamel dissolution and its prevention. In this paper the mechanism of dental enamel dissolution is discussed. Special attention is given to the anisotropic solubility behaviour (hollow tube formation) of demineralized enamel crystallites. The combined evidence strongly indicates that this peculiar dissolution behaviour is caused by dislocations. The dislocations--linear lattice defects--are present in the crystallite center and are the cause of two active dissolution sites in each crystallite. Initial as well as later stages in the caries process are discussed. Experimental evidence is presented which indicates that the active sites can be inactivated by agents like EHDP and MFP. After inactivation, acid penetration is either prevented or strongly retarded."}
{"id": "PMID:233841", "title": "Alterations in murine delayed type hypersensitivity responses by delta-8-THC and cannabinol.", "content": "The ability of cannabinol and delta-8-tetrahydrocannabinol (delta-8-THC), two cannabinoid marihuana components, to modify delayed-type hypersensitivity (DTH) to sheep red blood cells (SRBC) was investigated in mice. Reduction of DTH reactivity by cannabinol required multiple, daily, postimmunization drug administration. Neither multiple preimmunization dosings nor a single postimmunization dosing was effective. Delta-8-THC produced moderate (13-33%) suppression of DTH reactivity only upon multiple, preimmunization treatments, whereas postimmunization administration only delayed peak DTH reactivity 24 hours without altering the absolute response level. These results indicate that delta-8-THC and cannabinol possess slight to moderate activity in the suppression of DTH.", "contents": "Alterations in murine delayed type hypersensitivity responses by delta-8-THC and cannabinol. The ability of cannabinol and delta-8-tetrahydrocannabinol (delta-8-THC), two cannabinoid marihuana components, to modify delayed-type hypersensitivity (DTH) to sheep red blood cells (SRBC) was investigated in mice. Reduction of DTH reactivity by cannabinol required multiple, daily, postimmunization drug administration. Neither multiple preimmunization dosings nor a single postimmunization dosing was effective. Delta-8-THC produced moderate (13-33%) suppression of DTH reactivity only upon multiple, preimmunization treatments, whereas postimmunization administration only delayed peak DTH reactivity 24 hours without altering the absolute response level. These results indicate that delta-8-THC and cannabinol possess slight to moderate activity in the suppression of DTH."}
{"id": "PMID:233842", "title": "Restoration by levamisole of rosette-forming cells inhibited by histamine, db-CAMP and adenosine.", "content": "Db-cAMP and adenosine in vitro markedly inhibited the E-rosette formation of peripheral T-cells of healthy subjects. Histamine in vitro also inhibited the E-rosette formation, but only in patients with allergic disorders. Levamisole in vitro significantly restored the E-rosette formation of T-cells inhibited by db-cAMP, adenosine and histamine.", "contents": "Restoration by levamisole of rosette-forming cells inhibited by histamine, db-CAMP and adenosine. Db-cAMP and adenosine in vitro markedly inhibited the E-rosette formation of peripheral T-cells of healthy subjects. Histamine in vitro also inhibited the E-rosette formation, but only in patients with allergic disorders. Levamisole in vitro significantly restored the E-rosette formation of T-cells inhibited by db-cAMP, adenosine and histamine."}
{"id": "PMID:233846", "title": "[Physiology of smell and taste].", "content": "The functional organization of olfaction and taste are briefly discussed in morphological, physiological, biochemical and behavioural terms. Olfaction in animals serves often for long range navigational purposes whereas taste acts as a close up \"last moment food checking system\". Special attention is given to the coding problems in both systems. In taste, the spatial coding mode is prevalent. In olfaction a very complex coding system exists, which used temporal as well as spatial means and in which a whole set of olfactory nerve fibers is activated during the transmission of any specific odor information, each fiber of the set discharging at a specific impulse pattern. The role of the olfactory bulb is seen as an integrating center with the capabilities for short and long term information storage. The impact of von B\u00e9k\u00e9sy's microstimulation experiments on the physiology of taste is discussed. Research on taste modifiers such as gymnemic acid or of the taste modifying protein \"miraculin\" enrich our present understanding of the interaction between taste stimulants and the chemoreceptor sites in the taste buds.", "contents": "[Physiology of smell and taste]. The functional organization of olfaction and taste are briefly discussed in morphological, physiological, biochemical and behavioural terms. Olfaction in animals serves often for long range navigational purposes whereas taste acts as a close up \"last moment food checking system\". Special attention is given to the coding problems in both systems. In taste, the spatial coding mode is prevalent. In olfaction a very complex coding system exists, which used temporal as well as spatial means and in which a whole set of olfactory nerve fibers is activated during the transmission of any specific odor information, each fiber of the set discharging at a specific impulse pattern. The role of the olfactory bulb is seen as an integrating center with the capabilities for short and long term information storage. The impact of von B\u00e9k\u00e9sy's microstimulation experiments on the physiology of taste is discussed. Research on taste modifiers such as gymnemic acid or of the taste modifying protein \"miraculin\" enrich our present understanding of the interaction between taste stimulants and the chemoreceptor sites in the taste buds."}
{"id": "PMID:233850", "title": "Cytomegalovirus infection: a seroepidemiologic comparison of nuns and women from a venereal disease clinic.", "content": "A seroepidemiologic study of prevalence of antibody to cytomegalovirus (CMV) was simultaneously done in four populations: group I, nuns working as nurses or school teachers; group II, women admitted to a upper socioeconomic private hospital; group III, women admitted to a lower socioeconomic county hospital, and group and IV women attending a veneral disease clinic. Groups II, III and IV, were not statistically different and showed an abrupt rise in antibody prevalence during your adulthood. Group I, however, did not show the expected abrupt rise in antibody prevalence during young adulthood, and the prevalence in this group was singificantly lower than that in the other three groups at all but the oldest age range. These differences could not be accounted for by race, socioeconomic status or respiratory exposure to CMV. The data suggest that there may be more than one mechanism of CMV transmission and that venereal or intimate salivary contact may be a significant mode of spread in adults.", "contents": "Cytomegalovirus infection: a seroepidemiologic comparison of nuns and women from a venereal disease clinic. A seroepidemiologic study of prevalence of antibody to cytomegalovirus (CMV) was simultaneously done in four populations: group I, nuns working as nurses or school teachers; group II, women admitted to a upper socioeconomic private hospital; group III, women admitted to a lower socioeconomic county hospital, and group and IV women attending a veneral disease clinic. Groups II, III and IV, were not statistically different and showed an abrupt rise in antibody prevalence during your adulthood. Group I, however, did not show the expected abrupt rise in antibody prevalence during young adulthood, and the prevalence in this group was singificantly lower than that in the other three groups at all but the oldest age range. These differences could not be accounted for by race, socioeconomic status or respiratory exposure to CMV. The data suggest that there may be more than one mechanism of CMV transmission and that venereal or intimate salivary contact may be a significant mode of spread in adults."}
{"id": "PMID:233851", "title": "Seroepidemiology of human papovaviruses. Discovery of virgin populations and some unusual patterns of antibody prevalence among remote peoples of the world.", "content": "A total of 1544 sera from 28 diverse and mainly isolated populations were examined for HI antibody to BK virus. A few extremely isolated populations were found with negligible or absent exposure to the virus, but in most populations, remote or cosmopolitan, antibody appeared in increasing prevalence during early childhood and remained stable throughout adult life. Antibody acquisition and prevalence rates in individual families reflected that of the general population. Examined for HI antibody to JC virus were 393 sera from 9 of the 28 populations. Age acquisition and prevalence rates of antibody were similar to those of BK virus, but experience with the 2 viruses was found to occur independently in several population groups, i.e., high exposure to BK with low exposure to JC, or vice-versa. Examined for neurtralizing antibody to SV40 were 151 sera with and without BK HI antibody in individuals from several primitive populations. SV40 antibody, mainly in low titer, occurred in 35% of the BK-positive group, but only 5% of the BK-negative group, suggesting that infection with BK or a closely related virus is responsible for antibody directed against SV40 in most humans unexposed to known vaccine or monkey sources of SV40 infection.", "contents": "Seroepidemiology of human papovaviruses. Discovery of virgin populations and some unusual patterns of antibody prevalence among remote peoples of the world. A total of 1544 sera from 28 diverse and mainly isolated populations were examined for HI antibody to BK virus. A few extremely isolated populations were found with negligible or absent exposure to the virus, but in most populations, remote or cosmopolitan, antibody appeared in increasing prevalence during early childhood and remained stable throughout adult life. Antibody acquisition and prevalence rates in individual families reflected that of the general population. Examined for HI antibody to JC virus were 393 sera from 9 of the 28 populations. Age acquisition and prevalence rates of antibody were similar to those of BK virus, but experience with the 2 viruses was found to occur independently in several population groups, i.e., high exposure to BK with low exposure to JC, or vice-versa. Examined for neurtralizing antibody to SV40 were 151 sera with and without BK HI antibody in individuals from several primitive populations. SV40 antibody, mainly in low titer, occurred in 35% of the BK-positive group, but only 5% of the BK-negative group, suggesting that infection with BK or a closely related virus is responsible for antibody directed against SV40 in most humans unexposed to known vaccine or monkey sources of SV40 infection."}
{"id": "PMID:233853", "title": "Common misconceptions.", "content": "Certain misconceptions about the law are common among physicians. The purpose of the legal system is to resolve disputes rather than dispense \"justice.\" The rules of law are neither stable nor clear. Truth cannot be recovered for purposes of litigation; therefore, the evidence alone must determine the merit of a case. Many factors other than merit may also contribute substantially to the outcome of litigation.", "contents": "Common misconceptions. Certain misconceptions about the law are common among physicians. The purpose of the legal system is to resolve disputes rather than dispense \"justice.\" The rules of law are neither stable nor clear. Truth cannot be recovered for purposes of litigation; therefore, the evidence alone must determine the merit of a case. Many factors other than merit may also contribute substantially to the outcome of litigation."}
{"id": "PMID:233854", "title": "The legal setting in prescribing drugs.", "content": "By training and experience physicians generally prescribe drugs with only the patient in mind. In today's environment it is essential that the physician stop and think of himself also. We are all aware of malpractice problems, which begin in the physician's office or at the hospital and, if severe, end in court. The ophthalmologist must now consider what a disgruntled patient can find in writing to use in court. Hospital records and physician's charts are now just the beginning point. The Physician's Desk Reference (PDR), the published literature, the package insert, the promotional material of pharmaceutical companies, the internal records of drug companies, the pharmacists' records, and the data now obtainable from government agencies all provide happy hunting grounds for a competent plaintiff's attorney. The ophthalmologist needs to be keenly aware of these potentially adverse resources and how they can be used against him. He also needs to know the alternatives available to him. Once these matters are brought into clear perspective, both the patient and the ophthalmologist will be better off.", "contents": "The legal setting in prescribing drugs. By training and experience physicians generally prescribe drugs with only the patient in mind. In today's environment it is essential that the physician stop and think of himself also. We are all aware of malpractice problems, which begin in the physician's office or at the hospital and, if severe, end in court. The ophthalmologist must now consider what a disgruntled patient can find in writing to use in court. Hospital records and physician's charts are now just the beginning point. The Physician's Desk Reference (PDR), the published literature, the package insert, the promotional material of pharmaceutical companies, the internal records of drug companies, the pharmacists' records, and the data now obtainable from government agencies all provide happy hunting grounds for a competent plaintiff's attorney. The ophthalmologist needs to be keenly aware of these potentially adverse resources and how they can be used against him. He also needs to know the alternatives available to him. Once these matters are brought into clear perspective, both the patient and the ophthalmologist will be better off."}
{"id": "PMID:233856", "title": "The neuro-ophthalmology trap: failure to diagnose.", "content": "A failure to diagnose was the basis for most of a series of 35 malpractice suits filed against ophthalmologists and other physicians. All of these cases presented problems in neuro-ophthalmologic diagnosis. Selected summaries illustrate typical diagnostic pitfalls. \"Creative\" consultation reports may be one effective prophylactic measure against such legal actions.", "contents": "The neuro-ophthalmology trap: failure to diagnose. A failure to diagnose was the basis for most of a series of 35 malpractice suits filed against ophthalmologists and other physicians. All of these cases presented problems in neuro-ophthalmologic diagnosis. Selected summaries illustrate typical diagnostic pitfalls. \"Creative\" consultation reports may be one effective prophylactic measure against such legal actions."}
{"id": "PMID:233857", "title": "Special problems in ophthalmic subspecialties.", "content": "A study of 276 medicolegal cases disclosed the number in various ophthalmic subspecialties. The medical reasons for filing these claims were usually based upon omission or commission of acts fundamental to good basic ophthalmology, not the omission of sophisticated procedures. Among the lesions were that physicians should plan for the care of emergencies, use few types of drugs, order roentgenograms if suspicions arise, use consultants, stay well within one's level of competence, and document everything.", "contents": "Special problems in ophthalmic subspecialties. A study of 276 medicolegal cases disclosed the number in various ophthalmic subspecialties. The medical reasons for filing these claims were usually based upon omission or commission of acts fundamental to good basic ophthalmology, not the omission of sophisticated procedures. Among the lesions were that physicians should plan for the care of emergencies, use few types of drugs, order roentgenograms if suspicions arise, use consultants, stay well within one's level of competence, and document everything."}
{"id": "PMID:233858", "title": "Comparison of state legislation regarding professional liability.", "content": "The so-called malpractice crisis of the mid-1970s alerted physicians to the need for legislative involvement in order to achieve needed malpractice tort reform. There has been a positive effort to modify the medical liability situation in each of our 50 states. A review of this legislative activity from 1975 through 1977 is presented. It is anticipated that a new malpractice crisis may develop during the early 1980s. Actuarial data now being collected plus the effects of such innovations as arbitration, pretrial screening panels, collateral source rules, and periodic funding of malpractice claims may provide an equitable approach to any future malpractice tort reform.", "contents": "Comparison of state legislation regarding professional liability. The so-called malpractice crisis of the mid-1970s alerted physicians to the need for legislative involvement in order to achieve needed malpractice tort reform. There has been a positive effort to modify the medical liability situation in each of our 50 states. A review of this legislative activity from 1975 through 1977 is presented. It is anticipated that a new malpractice crisis may develop during the early 1980s. Actuarial data now being collected plus the effects of such innovations as arbitration, pretrial screening panels, collateral source rules, and periodic funding of malpractice claims may provide an equitable approach to any future malpractice tort reform."}
{"id": "PMID:233859", "title": "Some medicolegal tips.", "content": "The purposes for each type of medical record are critical legal determinants for its content. Deposition is the most important single step in the litigation process. The uses for a deposition greatly exceed the mere discovery of fact. The weight given the testimony of witnesses by a jury is affected by many subtle factors, including professional demeanor, attitude, manner of dress, ability to communicate and recollect, and prior inconsistent statements.", "contents": "Some medicolegal tips. The purposes for each type of medical record are critical legal determinants for its content. Deposition is the most important single step in the litigation process. The uses for a deposition greatly exceed the mere discovery of fact. The weight given the testimony of witnesses by a jury is affected by many subtle factors, including professional demeanor, attitude, manner of dress, ability to communicate and recollect, and prior inconsistent statements."}
{"id": "PMID:233860", "title": "Suprathreshold static perimetry in glaucoma and other optic nerve disease.", "content": "Comparisons between automated suprathreshold static perimetry and manual kinetic perimetry were performed for 226 eyes with glaucoma or ocular hypertension, and 147 eyes with other optic nerve disease. Both techniques produced similar high detection rates for glaucomatous visual field defects, whereas suprathreshold static perimetry performed significantly better than kinetic testing in optic nerve disease other than glaucoma. It is concluded that automated suprathreshold static perimetry is an excellent quantitative screening technique for detecting visual field defects.", "contents": "Suprathreshold static perimetry in glaucoma and other optic nerve disease. Comparisons between automated suprathreshold static perimetry and manual kinetic perimetry were performed for 226 eyes with glaucoma or ocular hypertension, and 147 eyes with other optic nerve disease. Both techniques produced similar high detection rates for glaucomatous visual field defects, whereas suprathreshold static perimetry performed significantly better than kinetic testing in optic nerve disease other than glaucoma. It is concluded that automated suprathreshold static perimetry is an excellent quantitative screening technique for detecting visual field defects."}
{"id": "PMID:233862", "title": "Clinical experiences with the use of an automated perimeter (Octopus) in the diagnosis and management of patients with glaucoma and neurologic diseases.", "content": "This is a study of 59 patients, 42 with glaucoma and 17 with neurological disease, to compare the Octopus automated perimeter with the conventional Goldmann and Tubinger perimeters for detection and assessment of visual field defects. We believe the Octopus automated perimeter is an excellent method for screening patients suspected of glaucoma and can be expected to identify over 90% of the patients actually having visual field loss due to glaucoma. In patients with neurological disease, the Goldmann perimeter was superior to either the Octopus or Tubinger perimeters in providing clinically useful information.", "contents": "Clinical experiences with the use of an automated perimeter (Octopus) in the diagnosis and management of patients with glaucoma and neurologic diseases. This is a study of 59 patients, 42 with glaucoma and 17 with neurological disease, to compare the Octopus automated perimeter with the conventional Goldmann and Tubinger perimeters for detection and assessment of visual field defects. We believe the Octopus automated perimeter is an excellent method for screening patients suspected of glaucoma and can be expected to identify over 90% of the patients actually having visual field loss due to glaucoma. In patients with neurological disease, the Goldmann perimeter was superior to either the Octopus or Tubinger perimeters in providing clinically useful information."}
{"id": "PMID:233864", "title": "Uveitis: effect of vitrectomy combined with lensectomy.", "content": "Combined lensectomy-vitrectomy was performed on 25 eyes in 20 patients with cataracta complicata associated with uveitis from various etiologies. Postoperative follow-up averaged 15 months, with visual improvement in 24 of the 25 eyes. Primary cause of postoperative decreased vision was cystoid macular edema. Operative complications included retinal detachment and choroidal ischemia. The technique employed and the effect of lensectomy-vitrectomy on decreasing the number and severity of recurrent attacks of uveitis are discussed.", "contents": "Uveitis: effect of vitrectomy combined with lensectomy. Combined lensectomy-vitrectomy was performed on 25 eyes in 20 patients with cataracta complicata associated with uveitis from various etiologies. Postoperative follow-up averaged 15 months, with visual improvement in 24 of the 25 eyes. Primary cause of postoperative decreased vision was cystoid macular edema. Operative complications included retinal detachment and choroidal ischemia. The technique employed and the effect of lensectomy-vitrectomy on decreasing the number and severity of recurrent attacks of uveitis are discussed."}
{"id": "PMID:233865", "title": "The treatment of orbital rhabdomyosarcoma with irradiation and chemotherapy.", "content": "Fifty-eight patients with orbital rhabdomyosarcoma were treated with irradiation alone (25) or irradiation and chemotherapy (33) with follow-ups of 6 months to 14 years (mean 5.2 yr). At present, 74% are alive and 26% have died. Local control of the tumor was accomplished in 91% of cases. When local sinuses were invaded the survival rate was 55%. Chemotherapy appears to be of greatest value when disease is limited to the orbit. Irradiation or irradiation and chemotherapy should now be the treatment of choice for orbital rhabdomyosarcoma.", "contents": "The treatment of orbital rhabdomyosarcoma with irradiation and chemotherapy. Fifty-eight patients with orbital rhabdomyosarcoma were treated with irradiation alone (25) or irradiation and chemotherapy (33) with follow-ups of 6 months to 14 years (mean 5.2 yr). At present, 74% are alive and 26% have died. Local control of the tumor was accomplished in 91% of cases. When local sinuses were invaded the survival rate was 55%. Chemotherapy appears to be of greatest value when disease is limited to the orbit. Irradiation or irradiation and chemotherapy should now be the treatment of choice for orbital rhabdomyosarcoma."}
{"id": "PMID:233866", "title": "Diagnosis and management of cancer metastatic to the uvea: a study of 70 cases.", "content": "Although metastatic cancer to the uvea is reported to be the most common intraocular malignancy, most ophthalmologists have had little experience with its diagnosis and treatment. This report describes our experience with the diagnosis and management of 70 patients with metastatic cancer to the uvea. Many patients were evaluated with modern diagnostic modalities such as fluorescein angiography, ultrasonography, and the 32P test when indicated. Thirty-one percent of patients had no history of previous malignancy, and the ocular complaints represented the first symptoms of systemic cancer. The ocular malignancy often simulated better-known ophthalmic entities, and the referring diagnosis was correct in only 38% of cases. This series, therefore, reflects the clinical problem confronting the practicing ophthalmologist. About one-half of the patients were treated with external beam irradiation to the involved eye(s), which often resulted in dramatic resolution of the tumor and visual return. Other patients had either no treatment, chemotherapy, or enucleation in selected instances.", "contents": "Diagnosis and management of cancer metastatic to the uvea: a study of 70 cases. Although metastatic cancer to the uvea is reported to be the most common intraocular malignancy, most ophthalmologists have had little experience with its diagnosis and treatment. This report describes our experience with the diagnosis and management of 70 patients with metastatic cancer to the uvea. Many patients were evaluated with modern diagnostic modalities such as fluorescein angiography, ultrasonography, and the 32P test when indicated. Thirty-one percent of patients had no history of previous malignancy, and the ocular complaints represented the first symptoms of systemic cancer. The ocular malignancy often simulated better-known ophthalmic entities, and the referring diagnosis was correct in only 38% of cases. This series, therefore, reflects the clinical problem confronting the practicing ophthalmologist. About one-half of the patients were treated with external beam irradiation to the involved eye(s), which often resulted in dramatic resolution of the tumor and visual return. Other patients had either no treatment, chemotherapy, or enucleation in selected instances."}
{"id": "PMID:233868", "title": "Glaucoma and expulsive hemorrhage mechanisms in the Sturge-Weber syndrome.", "content": "An eye from an adult with Sturge-Weber syndrome and glaucoma is described histologically following enucleation for massive choroidal hemorrhage. The specimen is noted to contain hemangiomas of the episclera and choroid as well as a partial angle cleavage abnormality. Histologic evidence reviewed herein supports the concept that infantile glaucoma associated with this syndrome may be associated with marked filtration angle cleavage deformities. Some Sturge-Weber patients who develop unilateral glaucoma later as juveniles or adults appear to have milder expressions of angle cleavage abnormality or a forme fruste of this angle disorder. Any surgical procedure for this glaucoma preferably should be one which minimizes or eliminates operative hypotony, thus avoiding a possible expulsive hemorrhage.", "contents": "Glaucoma and expulsive hemorrhage mechanisms in the Sturge-Weber syndrome. An eye from an adult with Sturge-Weber syndrome and glaucoma is described histologically following enucleation for massive choroidal hemorrhage. The specimen is noted to contain hemangiomas of the episclera and choroid as well as a partial angle cleavage abnormality. Histologic evidence reviewed herein supports the concept that infantile glaucoma associated with this syndrome may be associated with marked filtration angle cleavage deformities. Some Sturge-Weber patients who develop unilateral glaucoma later as juveniles or adults appear to have milder expressions of angle cleavage abnormality or a forme fruste of this angle disorder. Any surgical procedure for this glaucoma preferably should be one which minimizes or eliminates operative hypotony, thus avoiding a possible expulsive hemorrhage."}
{"id": "PMID:233869", "title": "Automated pattern analysis of corneal endothelium.", "content": "A proper understanding of the endothelial cell morphology of the cornea is of great significance to the corneal surgeon. Specular microscopy allows direct visualization of endothelial cell morphology and a proper analysis of these data needs automated computerized type of systems. Automated pattern analysis seems to offer a good option in this direction. From our experience it appears that such systems can be used with great advantage in the analysis of endothelial cell morphology. The data obtained from such analysis help to develop some indices for various facets of endothelial cell morphology.", "contents": "Automated pattern analysis of corneal endothelium. A proper understanding of the endothelial cell morphology of the cornea is of great significance to the corneal surgeon. Specular microscopy allows direct visualization of endothelial cell morphology and a proper analysis of these data needs automated computerized type of systems. Automated pattern analysis seems to offer a good option in this direction. From our experience it appears that such systems can be used with great advantage in the analysis of endothelial cell morphology. The data obtained from such analysis help to develop some indices for various facets of endothelial cell morphology."}
{"id": "PMID:233871", "title": "Cinnamic aldehyde allergy.", "content": "Positive patch test reactions to 2% cinnamic aldehyde were obtained from 2.8% of 34 males and 9.1% of 55 females. The 9.1% female reactivity may be traceable to perfumed cosmetics. Simultaneous Jasmin allergy is documented as is the occurrence of alpha-amyl cinnamic aldehyde in synthetic Jasmin. The relevance of these reactions is discussed. In two of the patients a proper diagnosis was not made from the original contact history. Only after a screening tray demonstration of cinnamic aldehyde allergy could a relevant history be taken from these patients.", "contents": "Cinnamic aldehyde allergy. Positive patch test reactions to 2% cinnamic aldehyde were obtained from 2.8% of 34 males and 9.1% of 55 females. The 9.1% female reactivity may be traceable to perfumed cosmetics. Simultaneous Jasmin allergy is documented as is the occurrence of alpha-amyl cinnamic aldehyde in synthetic Jasmin. The relevance of these reactions is discussed. In two of the patients a proper diagnosis was not made from the original contact history. Only after a screening tray demonstration of cinnamic aldehyde allergy could a relevant history be taken from these patients."}
{"id": "PMID:233872", "title": "Skin reactions to propylene glycol.", "content": "Propylene glycol (PG), ethylene glycol (EG), and polyethylene glycol 400 (PEG 400) were tested, as is, in a total of 1,556 cases of eczema using the chamber test method. All the year round, the number of positive reactions to PG was 12.5% to EG 4.9%, and to PEG 400 0.3%. A total of 30% of the positive reactions to PG were allergic in appearance. Also the new fatty alcohol-PG bases of Metosyn ointment and Topilar ointment as well as Metosyn ointment (fluocinonide) itself provoked reactions in a great number of patients with positive reactions to PG, as is. The reactions to PG were considered to be truly allergic in four cases. In them, positive reactions were elicited by testing with high dilutions of PG and by applying the glycol in the patients' armpits as an open test. It is concluded that PG and topical preparations containing it in high concentrations should not be used with occlusion, and that allergic reactions must be watched.", "contents": "Skin reactions to propylene glycol. Propylene glycol (PG), ethylene glycol (EG), and polyethylene glycol 400 (PEG 400) were tested, as is, in a total of 1,556 cases of eczema using the chamber test method. All the year round, the number of positive reactions to PG was 12.5% to EG 4.9%, and to PEG 400 0.3%. A total of 30% of the positive reactions to PG were allergic in appearance. Also the new fatty alcohol-PG bases of Metosyn ointment and Topilar ointment as well as Metosyn ointment (fluocinonide) itself provoked reactions in a great number of patients with positive reactions to PG, as is. The reactions to PG were considered to be truly allergic in four cases. In them, positive reactions were elicited by testing with high dilutions of PG and by applying the glycol in the patients' armpits as an open test. It is concluded that PG and topical preparations containing it in high concentrations should not be used with occlusion, and that allergic reactions must be watched."}
{"id": "PMID:233873", "title": "The patch test--who should and should not use it and why.", "content": "Since its introduction into medicine by Joseph Jadassohn in 1895, the patch test has proven its supreme value in tens of thousands of cases and in research. But emphasis must be placed on the grave errors which can occur when the test is used improperly. Errors are common in the direction of both false positives and false negatives. Common causes of errors are described in detail. The conclusion is drawn that this valuable test had best be used only by those who have been adequately trained and who can apply it regularly on a sufficiently large number of selected patients.", "contents": "The patch test--who should and should not use it and why. Since its introduction into medicine by Joseph Jadassohn in 1895, the patch test has proven its supreme value in tens of thousands of cases and in research. But emphasis must be placed on the grave errors which can occur when the test is used improperly. Errors are common in the direction of both false positives and false negatives. Common causes of errors are described in detail. The conclusion is drawn that this valuable test had best be used only by those who have been adequately trained and who can apply it regularly on a sufficiently large number of selected patients."}
{"id": "PMID:233889", "title": "Relative irritancy of free fatty acids of different chain length.", "content": "Free fatty acids of human skin surface lipids have previously been implicated in the pathogenesis of acne vulgaris because of their apparent irritant and comedogenic properties. Prior studies on the relative irritancy of free fatty acids revealed the saturated C8 to C14 fatty acids and a C18 dienoic unsaturated fatty acid (linoleic) to be most irritating. Saturated free fatty acids from C3 to C18, and unsaturated C18 free fatty acids were applied daily under occlusive patch tests to human skin until detectable erythema appeared. The most irritating fatty acids were C8 through C12. Of the unsaturated fatty acids tested, only linoleic acid produced irritation.", "contents": "Relative irritancy of free fatty acids of different chain length. Free fatty acids of human skin surface lipids have previously been implicated in the pathogenesis of acne vulgaris because of their apparent irritant and comedogenic properties. Prior studies on the relative irritancy of free fatty acids revealed the saturated C8 to C14 fatty acids and a C18 dienoic unsaturated fatty acid (linoleic) to be most irritating. Saturated free fatty acids from C3 to C18, and unsaturated C18 free fatty acids were applied daily under occlusive patch tests to human skin until detectable erythema appeared. The most irritating fatty acids were C8 through C12. Of the unsaturated fatty acids tested, only linoleic acid produced irritation."}
{"id": "PMID:233890", "title": "Cinnamic aldehyde in toothpaste. 1. Clinical aspects and patch tests.", "content": "Although cinnamon is known to cause dermatitis in bakers and confectioners, it has only rarely been reported as causing trouble in food or cosmetics. A newly-formulated 'spicy' toothpaste containing cinnamon as a flavouring agent was the cause of oral symptoms in eight patients referred to clinics in Buckinghamshire and in Malm\u00f6 and in a further eight patients discovered subsequently. Similar symptoms and patch test results were observed independently at both centres. Positive reactions were obtained with 1% cinnamic aldehyde in 15 out of 16 patients tested. Only one patient reacted to a standard sample of balsam of Peru (25% in petrolatum).", "contents": "Cinnamic aldehyde in toothpaste. 1. Clinical aspects and patch tests. Although cinnamon is known to cause dermatitis in bakers and confectioners, it has only rarely been reported as causing trouble in food or cosmetics. A newly-formulated 'spicy' toothpaste containing cinnamon as a flavouring agent was the cause of oral symptoms in eight patients referred to clinics in Buckinghamshire and in Malm\u00f6 and in a further eight patients discovered subsequently. Similar symptoms and patch test results were observed independently at both centres. Positive reactions were obtained with 1% cinnamic aldehyde in 15 out of 16 patients tested. Only one patient reacted to a standard sample of balsam of Peru (25% in petrolatum)."}
{"id": "PMID:233891", "title": "Sensitivity to cinnamic aldehyde in a toothpaste. 2. Further studies.", "content": "The authors carried out further studies to assess the significance of the findings of patients sensitive to cinnamic aldehyde in a toothpaste. Selected groups of patients in whom sensitivity to this might have been overlooked were patch-tested. With the exception of three patients, two with cosmetic sensitivity and one with hand eczema, the results were negative. The frequency of use of the original toothpaste was assessed among patients attending the clinic and this was followed by a circular letter to general practitioners and dentists inviting referral of patients with oral symptoms. As a result, five further cases, four of whom gave positive patch test reactions to cinnamic aldehyde, were discovered. The authors emphasize the importance of attempting to obtain accurate information as quickly as possible when 'new' or hitherto unsuspected allergens are implicated.", "contents": "Sensitivity to cinnamic aldehyde in a toothpaste. 2. Further studies. The authors carried out further studies to assess the significance of the findings of patients sensitive to cinnamic aldehyde in a toothpaste. Selected groups of patients in whom sensitivity to this might have been overlooked were patch-tested. With the exception of three patients, two with cosmetic sensitivity and one with hand eczema, the results were negative. The frequency of use of the original toothpaste was assessed among patients attending the clinic and this was followed by a circular letter to general practitioners and dentists inviting referral of patients with oral symptoms. As a result, five further cases, four of whom gave positive patch test reactions to cinnamic aldehyde, were discovered. The authors emphasize the importance of attempting to obtain accurate information as quickly as possible when 'new' or hitherto unsuspected allergens are implicated."}
{"id": "PMID:233892", "title": "Contact dermatitis in patients with leg ulcers.", "content": "The incidence of contact allergy to 63 substances, including active principles and excipients used in a variety of topical preparations, has been studied by patch testing in 306 patients being treated conservatively for stasis dermatitis with or without ulceration. Positive reactions to one or more test compounds were recorded in 177 patients. The main offenders among drugs were neomycin, sulphonamide and promethazine; among the excipients, they were parabens, lanolins and benzoyl peroxide. Frequent reactions were observed to certain substances of the 'para' group, benzocaine, diaminodiphenylmethane, aniline and paraphenylendiamine, with the first three acting mainly as indicators of cross-sensitization. The extension and spread of allergic dermatitis can also be produced by drugs administered systematically. Recognition of the allergens responsible for allergic contact dermatitis arising at the lower leg site is a necessary condition if chronicity and spread of the dermatitis are to be prevented. For the same reason it is important to restrict topical applications to non-allergic substances.", "contents": "Contact dermatitis in patients with leg ulcers. The incidence of contact allergy to 63 substances, including active principles and excipients used in a variety of topical preparations, has been studied by patch testing in 306 patients being treated conservatively for stasis dermatitis with or without ulceration. Positive reactions to one or more test compounds were recorded in 177 patients. The main offenders among drugs were neomycin, sulphonamide and promethazine; among the excipients, they were parabens, lanolins and benzoyl peroxide. Frequent reactions were observed to certain substances of the 'para' group, benzocaine, diaminodiphenylmethane, aniline and paraphenylendiamine, with the first three acting mainly as indicators of cross-sensitization. The extension and spread of allergic dermatitis can also be produced by drugs administered systematically. Recognition of the allergens responsible for allergic contact dermatitis arising at the lower leg site is a necessary condition if chronicity and spread of the dermatitis are to be prevented. For the same reason it is important to restrict topical applications to non-allergic substances."}
{"id": "PMID:233893", "title": "The histopathology of fiberglass dermatitis in relation to von Hebra's concept of eczema.", "content": "A group of 36 normal control persons was patch-tested with glass fibers. The tested filaments had a length of about 3 to 5 mm and a diameter of 9 to 13 microns. The glass fibers were obtained from the normal production process. They were coated with cured epoxy resin. A group of 29 normal control persons was tested with the same type of fibers from which the epoxy finish had been burned off. Another group of 36 persons was patch-tested with ultrasmall glass globes with a diameter of 10 to 15 microns. Coated and uncoated glass globules were tested. On every person 5 patch tests with the same material were done. They were removed after 1, 5, 24, 48 and 72 h. On coated fiber, 12 of 36 tested people reacted with either a + or a ++ reaction. On the uncoated fibers a reaction could be noted in 10 out of 29 persons. The patch tests with coated as well as uncoated glass globules were all negative. A total of 60 biopsies was performed in those cases where + or ++ reactions were noted. The histological examination of the biopsies showed no differences between the reactions on coated and uncoated fibers. The skin reactions to glass fiber showed, besides microtraumatic changes, several histological characteristics of an eczematous reaction, like spongiosis and perivascular lymphocytic infiltration. The importance of these findings is discussed. It is emphasized that histological alterations are only one of the six points which must be taken into account when the diagnosis of eczema is considered.", "contents": "The histopathology of fiberglass dermatitis in relation to von Hebra's concept of eczema. A group of 36 normal control persons was patch-tested with glass fibers. The tested filaments had a length of about 3 to 5 mm and a diameter of 9 to 13 microns. The glass fibers were obtained from the normal production process. They were coated with cured epoxy resin. A group of 29 normal control persons was tested with the same type of fibers from which the epoxy finish had been burned off. Another group of 36 persons was patch-tested with ultrasmall glass globes with a diameter of 10 to 15 microns. Coated and uncoated glass globules were tested. On every person 5 patch tests with the same material were done. They were removed after 1, 5, 24, 48 and 72 h. On coated fiber, 12 of 36 tested people reacted with either a + or a ++ reaction. On the uncoated fibers a reaction could be noted in 10 out of 29 persons. The patch tests with coated as well as uncoated glass globules were all negative. A total of 60 biopsies was performed in those cases where + or ++ reactions were noted. The histological examination of the biopsies showed no differences between the reactions on coated and uncoated fibers. The skin reactions to glass fiber showed, besides microtraumatic changes, several histological characteristics of an eczematous reaction, like spongiosis and perivascular lymphocytic infiltration. The importance of these findings is discussed. It is emphasized that histological alterations are only one of the six points which must be taken into account when the diagnosis of eczema is considered."}
{"id": "PMID:233894", "title": "Occupational dermatitis in a 10-year material.", "content": "This study included 1,752 patients considered to have occupational dermatoses. The most common diagnosis was contact dermatitis. The dermatitis was of an allergic type in three-quarters of men and in half of women. One-fifth of the women with irritant contact dermatitis had an atopic history. Contact dermatitis was localized on the hands in 94% of women and in 84% of men. The most common allergens in men were chromium, rubber and plastic, and in women nickel, rubber and chromium. Chromium allergy occurred in four-fifths of the men in the building, metal and tanning industries. In one-fifth of the women, nickel allergy developed in cleaning work. Rubber allergy developed in the rubber industry in one-fifth of the cases. Half of the women with contact dermatitis were engaged in either nursing or cleaning work. A follow-up 2-3 years after treatment of 555 patients with contact dermatitis was completed by means of questionnaires. The eczema was healed in one-quarter of the patients, one-half had periodic symptoms, and one-quarter had permanent symptoms. The prognosis was the same for those who changed their work or stopped working as it was for those who continued their eczema-inducing work.", "contents": "Occupational dermatitis in a 10-year material. This study included 1,752 patients considered to have occupational dermatoses. The most common diagnosis was contact dermatitis. The dermatitis was of an allergic type in three-quarters of men and in half of women. One-fifth of the women with irritant contact dermatitis had an atopic history. Contact dermatitis was localized on the hands in 94% of women and in 84% of men. The most common allergens in men were chromium, rubber and plastic, and in women nickel, rubber and chromium. Chromium allergy occurred in four-fifths of the men in the building, metal and tanning industries. In one-fifth of the women, nickel allergy developed in cleaning work. Rubber allergy developed in the rubber industry in one-fifth of the cases. Half of the women with contact dermatitis were engaged in either nursing or cleaning work. A follow-up 2-3 years after treatment of 555 patients with contact dermatitis was completed by means of questionnaires. The eczema was healed in one-quarter of the patients, one-half had periodic symptoms, and one-quarter had permanent symptoms. The prognosis was the same for those who changed their work or stopped working as it was for those who continued their eczema-inducing work."}
{"id": "PMID:233897", "title": "Nonspecific activation of murine lymphocytes. I. Proliferation and polyclonal activation induced by 2-mercaptoethanol and alpha-thioglycerol.", "content": "The effect of 2-mercaptoethanol (2-ME) and alpha-thioglycerol (alpha TG) on proliferation and polyclonal activation of lymphocytes was studied in cultures of spleen cells from C3H mice. Inclusion in serum-free or serum-containing medium of the optimal concentration (5 x 10(-5) M) of either 2-ME or alpha TG resulted in highly significant uptake and incorporation of tritiated thymidine ([3H]TdR) into DNA and in morphological blast transformation. These phenomena were dose-dependent, with both lower and higher doses causing less marked effects. The kinetic peak of these responses was found to occur at day 3 of culture. Improved cellular viability could not explain these results, because by day 3 there was no significant difference in viability between cells cultured in the presence or absence of 2-ME. 2-ME evoked a proliferative response in cultures of congenitally athymic (nu/nu) spleen cells that exhibited a similar but lower dose-response profile compared with that of heterozygous (nu/+) littermates. Cultures of bone marrow-derived (B) lymphocytes, generated by treatment of spleen cells with rabbit antithymocyte serum and complement, incorporated [3H]TdR to a degree at least equal to that of normal spleen cell cultures. Thymus-dependent (T) cells did not support significant 2-ME, alpha TG, or Concanavalin A responses in the absence of serum. However, when cultured in 5% fetal calf serum, definite T-cell responses occurred, though always of a lower magnitude than B-cell responses in this system. When the enriched B-cell and T-cell preparations were co-cultured, a synergistic response was noted. Macrophage dependency of the 2-ME and alpha TG effect was shown to be minimal. It is likely that the greater effectiveness of alpha TG relative to 2-ME is due to differences in the chemical structure of these two thiol compounds. The advantages of utilizing 2-ME and alpha TG as probes in the study of lymphocyte activation are evaluated and their possible mechanisms of action are discussed.", "contents": "Nonspecific activation of murine lymphocytes. I. Proliferation and polyclonal activation induced by 2-mercaptoethanol and alpha-thioglycerol. The effect of 2-mercaptoethanol (2-ME) and alpha-thioglycerol (alpha TG) on proliferation and polyclonal activation of lymphocytes was studied in cultures of spleen cells from C3H mice. Inclusion in serum-free or serum-containing medium of the optimal concentration (5 x 10(-5) M) of either 2-ME or alpha TG resulted in highly significant uptake and incorporation of tritiated thymidine ([3H]TdR) into DNA and in morphological blast transformation. These phenomena were dose-dependent, with both lower and higher doses causing less marked effects. The kinetic peak of these responses was found to occur at day 3 of culture. Improved cellular viability could not explain these results, because by day 3 there was no significant difference in viability between cells cultured in the presence or absence of 2-ME. 2-ME evoked a proliferative response in cultures of congenitally athymic (nu/nu) spleen cells that exhibited a similar but lower dose-response profile compared with that of heterozygous (nu/+) littermates. Cultures of bone marrow-derived (B) lymphocytes, generated by treatment of spleen cells with rabbit antithymocyte serum and complement, incorporated [3H]TdR to a degree at least equal to that of normal spleen cell cultures. Thymus-dependent (T) cells did not support significant 2-ME, alpha TG, or Concanavalin A responses in the absence of serum. However, when cultured in 5% fetal calf serum, definite T-cell responses occurred, though always of a lower magnitude than B-cell responses in this system. When the enriched B-cell and T-cell preparations were co-cultured, a synergistic response was noted. Macrophage dependency of the 2-ME and alpha TG effect was shown to be minimal. It is likely that the greater effectiveness of alpha TG relative to 2-ME is due to differences in the chemical structure of these two thiol compounds. The advantages of utilizing 2-ME and alpha TG as probes in the study of lymphocyte activation are evaluated and their possible mechanisms of action are discussed."}
{"id": "PMID:233898", "title": "Histocompatibility antigen-activated cytotoxic T lymphocytes. I. Estimates of the absolute frequency of killer cells generated in vitro.", "content": "A sensitive procedure employing limiting dilution of activated lymphocytes and 51Cr release from highly labeled target cells was used to derive minimal estimates of the absolute frequency of cytotoxic T lymphocytes (CTL) present in a population of mouse lymphocytes activated to alloantigens of the major histocompatibility complex in bulk mixed lymphocyte cultures. From this figure (0.7-1.2%), the maximal rate of target cell killing could be calculated to be approximately 4 targets/CTL/hour.", "contents": "Histocompatibility antigen-activated cytotoxic T lymphocytes. I. Estimates of the absolute frequency of killer cells generated in vitro. A sensitive procedure employing limiting dilution of activated lymphocytes and 51Cr release from highly labeled target cells was used to derive minimal estimates of the absolute frequency of cytotoxic T lymphocytes (CTL) present in a population of mouse lymphocytes activated to alloantigens of the major histocompatibility complex in bulk mixed lymphocyte cultures. From this figure (0.7-1.2%), the maximal rate of target cell killing could be calculated to be approximately 4 targets/CTL/hour."}
{"id": "PMID:233899", "title": "Histocompatibility antigen-activated cytotoxic T lymphocytes. II. Estimates of the frequency and specificity of precursors.", "content": "Using limiting dilutions of responding cells in mouse mixed leukocyte cultures, we obtained direct estimates of the minimum frequency of precursors of cytotoxic T lymphocytes (CTL.P) for a variety of antigens. Depending on the strain combination, there were as many as 4-15 CTL.P reactive to DBA/2 among 10(4) lymph node cells. Taking into account that only 5-10% of peripheral T lymphocytes have the potential to develop into cytotoxic T lymphocytes (CTLs) (6), this implies that at least 1-2% of all CTL.P are responsive to any given H-2 haplotype difference. Precursors of cytotoxic cells thus have the same high frequency of cells reactive to alloantigens of the major histocompatibility complex as found among proliferating cells in graft-vs.-host reactions and mixed lymphocyte interactions. The frequencies of CTL.P reactive to xenoantigens (rat) or trinitrophenyl-modified self were less than half the frequency of alloreactive CTL.P. A minority of the CTL.P specific for one H-2 haplotype were also reactive to a third party H-2 haplotype, presumably on the basis of recognition of shared determinants. By dilution of sensitized cells from single microcultures, it was shown that a single CTL.P undergoes a minimum of three to four cell divisions and generates at least 8-16 CTLs after antigenic activation.", "contents": "Histocompatibility antigen-activated cytotoxic T lymphocytes. II. Estimates of the frequency and specificity of precursors. Using limiting dilutions of responding cells in mouse mixed leukocyte cultures, we obtained direct estimates of the minimum frequency of precursors of cytotoxic T lymphocytes (CTL.P) for a variety of antigens. Depending on the strain combination, there were as many as 4-15 CTL.P reactive to DBA/2 among 10(4) lymph node cells. Taking into account that only 5-10% of peripheral T lymphocytes have the potential to develop into cytotoxic T lymphocytes (CTLs) (6), this implies that at least 1-2% of all CTL.P are responsive to any given H-2 haplotype difference. Precursors of cytotoxic cells thus have the same high frequency of cells reactive to alloantigens of the major histocompatibility complex as found among proliferating cells in graft-vs.-host reactions and mixed lymphocyte interactions. The frequencies of CTL.P reactive to xenoantigens (rat) or trinitrophenyl-modified self were less than half the frequency of alloreactive CTL.P. A minority of the CTL.P specific for one H-2 haplotype were also reactive to a third party H-2 haplotype, presumably on the basis of recognition of shared determinants. By dilution of sensitized cells from single microcultures, it was shown that a single CTL.P undergoes a minimum of three to four cell divisions and generates at least 8-16 CTLs after antigenic activation."}
{"id": "PMID:233900", "title": "Frequency of occurrence of idiotypes associated with anti-p-azophenylarsonate antibodies arising in mice immunologically suppressed with respect to a cross-reactive idiotype.", "content": "Inoculation of rabbit anti-idiotypic (anti-id) antibodies suppresses the subsequent appearance of a cross-reactive idiotype (CRI) associated with the anti-p-azophenylarsonate (anti-Ar) antibodies of A/J mice. Such suppressed mice produce normal concentrations of anti-Ar antibodies which lack the CRI, but against which anti-id antisera can be prepared. The anti-Ar antibodies of an individual, suppressed mouse do not in general share idiotype with anti-Ar antibodies of other A/J mice, either suppressed or nonsuppressed. The present experiments were undertaken to quantitate several \"private idiotypes\" in a large number of hyperimmunized A/J mice. Anti-Ar antibodies of three mice, suppressed for the CRI, were labeled with 125I and subjected to isoelectric focusing. Four single peaks, that were over 90% reactive with autologous antiid, were randomly selected for use as ligands in a radioimmunoassay, and ascitic fluids containing anti-Ar antibodies from 181 A/J mice were tested as inhibitors. Two of the four idiotypes could not be detected in any mouse other than the donor. The concentration of the idiotype was less than 1 part in 1,250 to less than 1 part in 25,000 of the anti-Ar antibody population; these are minimum values. A third idiotype was detected in 3 of the 181 mice, but at very low concentrations. The fourth idiotype was present in 28% of the mice, again at a low concentration. The data support the existence of a very large repertoire of anti-Ar antibodies in the A/J strain and are consistent with a process of random somatic mutation for generating diversity in hypervariable regions. It is proposed that the cross-reactive idiotype may be controlled by a germ line gene or a gene related to a germ line gene through a small number of somatic mutations; and that the idiotypes that were not detectable in other mice were the products of genes that had undergone extensive mutations, with a low probability of recurrence in other mice.", "contents": "Frequency of occurrence of idiotypes associated with anti-p-azophenylarsonate antibodies arising in mice immunologically suppressed with respect to a cross-reactive idiotype. Inoculation of rabbit anti-idiotypic (anti-id) antibodies suppresses the subsequent appearance of a cross-reactive idiotype (CRI) associated with the anti-p-azophenylarsonate (anti-Ar) antibodies of A/J mice. Such suppressed mice produce normal concentrations of anti-Ar antibodies which lack the CRI, but against which anti-id antisera can be prepared. The anti-Ar antibodies of an individual, suppressed mouse do not in general share idiotype with anti-Ar antibodies of other A/J mice, either suppressed or nonsuppressed. The present experiments were undertaken to quantitate several \"private idiotypes\" in a large number of hyperimmunized A/J mice. Anti-Ar antibodies of three mice, suppressed for the CRI, were labeled with 125I and subjected to isoelectric focusing. Four single peaks, that were over 90% reactive with autologous antiid, were randomly selected for use as ligands in a radioimmunoassay, and ascitic fluids containing anti-Ar antibodies from 181 A/J mice were tested as inhibitors. Two of the four idiotypes could not be detected in any mouse other than the donor. The concentration of the idiotype was less than 1 part in 1,250 to less than 1 part in 25,000 of the anti-Ar antibody population; these are minimum values. A third idiotype was detected in 3 of the 181 mice, but at very low concentrations. The fourth idiotype was present in 28% of the mice, again at a low concentration. The data support the existence of a very large repertoire of anti-Ar antibodies in the A/J strain and are consistent with a process of random somatic mutation for generating diversity in hypervariable regions. It is proposed that the cross-reactive idiotype may be controlled by a germ line gene or a gene related to a germ line gene through a small number of somatic mutations; and that the idiotypes that were not detectable in other mice were the products of genes that had undergone extensive mutations, with a low probability of recurrence in other mice."}
{"id": "PMID:233901", "title": "Generation of both cross-reactive and virus-specific T-cell populations after immunization with serologically distinct influenza A viruses.", "content": "Specificity of cytotoxic T-cell function was investigated for a range of different influenza viruses. T cells from mice immunized with A or B strain influenza viruses, or with vaccinia virus, showed reciprocal exclusion of cytotoxicity. Extensive cross-reactivity was, however, found for lymphocyte populations from mice infected with a variety of serologically distinct influenza A viruses, though serum antibodies did not cross-react when tested in a radioimmunoassay using comparable target cells as immunoadsorbents. This apparent lack of T-cell specificity was recognized for immune spleen cells generated after intraperitoneal inoculation of high titers of virus, and for mediastinal lymph node populations from mice with pneumonia due to infection with much less virus. The phenomenon could not be explained on the basis of exposure to the chicken host component, which is common to A and B strain viruses. However, not all of the virus-immune T-cell clones are cross-reactive. Competitive-inhibition experiments indicate that a considerable proportion of the lymphocyte response is restricted to the immunizing virus. Even so, the less specific component is significant. Also, exposure to one type A virus was found to prime for an enhanced cell-mediated immunity response after challenge with a second, serologically different A strain virus.", "contents": "Generation of both cross-reactive and virus-specific T-cell populations after immunization with serologically distinct influenza A viruses. Specificity of cytotoxic T-cell function was investigated for a range of different influenza viruses. T cells from mice immunized with A or B strain influenza viruses, or with vaccinia virus, showed reciprocal exclusion of cytotoxicity. Extensive cross-reactivity was, however, found for lymphocyte populations from mice infected with a variety of serologically distinct influenza A viruses, though serum antibodies did not cross-react when tested in a radioimmunoassay using comparable target cells as immunoadsorbents. This apparent lack of T-cell specificity was recognized for immune spleen cells generated after intraperitoneal inoculation of high titers of virus, and for mediastinal lymph node populations from mice with pneumonia due to infection with much less virus. The phenomenon could not be explained on the basis of exposure to the chicken host component, which is common to A and B strain viruses. However, not all of the virus-immune T-cell clones are cross-reactive. Competitive-inhibition experiments indicate that a considerable proportion of the lymphocyte response is restricted to the immunizing virus. Even so, the less specific component is significant. Also, exposure to one type A virus was found to prime for an enhanced cell-mediated immunity response after challenge with a second, serologically different A strain virus."}
{"id": "PMID:233902", "title": "Genetic control of the immune response to nuclease. V. Genetic linkage and strain distribution of anti-nuclease idiotypes.", "content": "Rat antisera raised against anti-nuclease antibodies from mouse strains A/J and SJL detect strain-specific idiotypic determinants related to the antigen-combining site. These antisera have been used to investigate the genetic linkage and strain distribution of the anti-nuclease idiotypes. Despite the existence of an H-2-linked immune response gene controlling the humoral response to nuclease, expression of the A/J anti-nuclease idiotype has been shown to be independent of genes in the H-2 region: the A/J idiotype was present in immune sera from strains A/J (H-2a) and A.BY (H-2b) but absent in sera from strains B10 (H-2b) and B10.A (H-2a). An analysis of the segregation of the A/J idiotype in offspring of the backcross (A/J x B10.A) x B10.A demonstrated linkage to the Ig-1e heavy chain allotype markers. In a small sample of backcross animals a very high apparent recombination frequency was observed, but further backcross analyses and progeny testing of putative recombinant animals will be required to substantiate this observation. Analysis of the A/J and SJL anti-nuclease idiotype markers in the BALB/c, CB.20, and BAB.14 strains indicate that these idiotypic markers may permit mapping of distinct variable region genes.", "contents": "Genetic control of the immune response to nuclease. V. Genetic linkage and strain distribution of anti-nuclease idiotypes. Rat antisera raised against anti-nuclease antibodies from mouse strains A/J and SJL detect strain-specific idiotypic determinants related to the antigen-combining site. These antisera have been used to investigate the genetic linkage and strain distribution of the anti-nuclease idiotypes. Despite the existence of an H-2-linked immune response gene controlling the humoral response to nuclease, expression of the A/J anti-nuclease idiotype has been shown to be independent of genes in the H-2 region: the A/J idiotype was present in immune sera from strains A/J (H-2a) and A.BY (H-2b) but absent in sera from strains B10 (H-2b) and B10.A (H-2a). An analysis of the segregation of the A/J idiotype in offspring of the backcross (A/J x B10.A) x B10.A demonstrated linkage to the Ig-1e heavy chain allotype markers. In a small sample of backcross animals a very high apparent recombination frequency was observed, but further backcross analyses and progeny testing of putative recombinant animals will be required to substantiate this observation. Analysis of the A/J and SJL anti-nuclease idiotype markers in the BALB/c, CB.20, and BAB.14 strains indicate that these idiotypic markers may permit mapping of distinct variable region genes."}
{"id": "PMID:233903", "title": "Studies of the receptor for phage A25 in group A streptococci: the role of peptidoglycan in reversible adsorption.", "content": "Irreversible adsorption of a virulent phage, phage A25, to heat-killed streptococci, groups A, G, and A variant, has been achieved. Adsorption reflected the observed host range for phage A25 in that heat-killed group B cells were not able to inactivate the phage. Broken cells, cell walls, and peptidoglycan prepared from a group A strain K56 failed to adsorb the phage irreversibly, but retained the potential to carry out reversible adsorption. Experimental data including electron microscopy have demonstrated the specificity of reversible adsorption and have identified the peptidoglycan as a necessary cellular component of the receptor. The sensitivity of whole cells and purified peptidoglycan to muralytic enzymes suggests that the cell wall and peptidoglycan must be intact for optimal adsorption. In general the results are explained by postulating that adsorption of A25 phage particles to group A cells occurs by a two-step process; the first step involves recognition and reversible binding of the phage tail to the cell wall peptidoglycan, the second step is an irreversible reaction catalyzed by a yet unidentified cellular component which is destroyed when cells are ruptured.", "contents": "Studies of the receptor for phage A25 in group A streptococci: the role of peptidoglycan in reversible adsorption. Irreversible adsorption of a virulent phage, phage A25, to heat-killed streptococci, groups A, G, and A variant, has been achieved. Adsorption reflected the observed host range for phage A25 in that heat-killed group B cells were not able to inactivate the phage. Broken cells, cell walls, and peptidoglycan prepared from a group A strain K56 failed to adsorb the phage irreversibly, but retained the potential to carry out reversible adsorption. Experimental data including electron microscopy have demonstrated the specificity of reversible adsorption and have identified the peptidoglycan as a necessary cellular component of the receptor. The sensitivity of whole cells and purified peptidoglycan to muralytic enzymes suggests that the cell wall and peptidoglycan must be intact for optimal adsorption. In general the results are explained by postulating that adsorption of A25 phage particles to group A cells occurs by a two-step process; the first step involves recognition and reversible binding of the phage tail to the cell wall peptidoglycan, the second step is an irreversible reaction catalyzed by a yet unidentified cellular component which is destroyed when cells are ruptured."}
{"id": "PMID:233904", "title": "Spontaneous regression of Friend virus-induced erythroleukemia. I. The role of the helper murine leukemia virus component.", "content": "The RFV strain of the Friend virus complex induces an erythroleukemia that spontaneously regresses. The tropism of regressing Friend virus complex (RFV), which is conferred by its helper MuLV component, MuLV-RF, is different from that of the conventional virus strain, CFV. RFV is NB-tropic and CFV is N-tropic. Passage of nonregressing CFV through Fv-1 incompatible Swiss/ICR mice changed the tropism of CFV from N to NB and resulted in a virus strain which induced erythroleukemia that regressed. Passage of NB-tropic CFV back through Fv-1 compatible mice maintained NB-tropism and regression. Altering the quantity or type of helper MuLV in RFV complex by addition of Ri-MuLV inhibited regression in proportion to the amount of added Ri-MuLV. These studies indicate a relationship between a change in virus tropism to NB by passage in certain hosts (e.g., Swiss/ICR mice) and the ability of Friend virus to induce erythroleukemia that spontaneously regresses. MuLV-RF isolated from the RFV complex induced lymphocytic leukemia in newborn mice which regressed and caused the regression of CFV-induced erythroleukemia. MuLV-RF is NB-tropic, contains no spleen focus-forming virus (SFFV) activity and helps SFFV form spleen foci in genetically restrictive mice. Pseudotype viruses were prepared, consisting of MuLV-RF, or other MuLV's, and SFFV derived from FV-B. The pseudotype viruses each acquired the tropism of the MuLV used in rescue. The pseudotype prepared with MuLV-RF or another NB-tropic MuLV-F, but not the virus obtained by rescue with N-tropic MuLV-F, induced erythroleukemia that spontaneously regressed. These studies demonstrate that the ability of RFV to induce erythroleukemia that spontaneously regresses is due to its helper MuLV component.", "contents": "Spontaneous regression of Friend virus-induced erythroleukemia. I. The role of the helper murine leukemia virus component. The RFV strain of the Friend virus complex induces an erythroleukemia that spontaneously regresses. The tropism of regressing Friend virus complex (RFV), which is conferred by its helper MuLV component, MuLV-RF, is different from that of the conventional virus strain, CFV. RFV is NB-tropic and CFV is N-tropic. Passage of nonregressing CFV through Fv-1 incompatible Swiss/ICR mice changed the tropism of CFV from N to NB and resulted in a virus strain which induced erythroleukemia that regressed. Passage of NB-tropic CFV back through Fv-1 compatible mice maintained NB-tropism and regression. Altering the quantity or type of helper MuLV in RFV complex by addition of Ri-MuLV inhibited regression in proportion to the amount of added Ri-MuLV. These studies indicate a relationship between a change in virus tropism to NB by passage in certain hosts (e.g., Swiss/ICR mice) and the ability of Friend virus to induce erythroleukemia that spontaneously regresses. MuLV-RF isolated from the RFV complex induced lymphocytic leukemia in newborn mice which regressed and caused the regression of CFV-induced erythroleukemia. MuLV-RF is NB-tropic, contains no spleen focus-forming virus (SFFV) activity and helps SFFV form spleen foci in genetically restrictive mice. Pseudotype viruses were prepared, consisting of MuLV-RF, or other MuLV's, and SFFV derived from FV-B. The pseudotype viruses each acquired the tropism of the MuLV used in rescue. The pseudotype prepared with MuLV-RF or another NB-tropic MuLV-F, but not the virus obtained by rescue with N-tropic MuLV-F, induced erythroleukemia that spontaneously regressed. These studies demonstrate that the ability of RFV to induce erythroleukemia that spontaneously regresses is due to its helper MuLV component."}
{"id": "PMID:233905", "title": "Differences in pyrogen production by mononuclear phagocytes and by fibroblasts or HeLa cells.", "content": "Phagocytosis of bacteria stimulates \"professional\" phagocytes to produce and release endogenous pyrogen (EP), the protein that mediates fever. To determine whether \"nonprofessional\" phagocytes also have this capacity, mouse and human fibroblasts and HeLa cells were cultured after ingestion of latex or chicken erythrocytes (CE), and EP release into culture supernate measured by mouse assay. No detectable pyrogen was released by these cell types after phagocytosis, whereas both latex and CE stimulated EP production by cultured mouse macrophages. These studies support the hypothesis that only professional phagocytes of bone marrow origin synthesize EP and induce fever.", "contents": "Differences in pyrogen production by mononuclear phagocytes and by fibroblasts or HeLa cells. Phagocytosis of bacteria stimulates \"professional\" phagocytes to produce and release endogenous pyrogen (EP), the protein that mediates fever. To determine whether \"nonprofessional\" phagocytes also have this capacity, mouse and human fibroblasts and HeLa cells were cultured after ingestion of latex or chicken erythrocytes (CE), and EP release into culture supernate measured by mouse assay. No detectable pyrogen was released by these cell types after phagocytosis, whereas both latex and CE stimulated EP production by cultured mouse macrophages. These studies support the hypothesis that only professional phagocytes of bone marrow origin synthesize EP and induce fever."}
{"id": "PMID:233906", "title": "Independent populations of primed F1 guinea pig T lymphocytes respond to antigen-pulsed parental peritoneal exudate cells.", "content": "Thymus-dependent (T) lymphocytes from (2 x 13)F1 hybrid guinea pigs immunized to ovalbumin (OVA) in complete Freund's adjuvant can be stimulated to proliferate in vitro by antigen-pulsed peritoneal exudate cells (PECs) derived from either strain 2 or strain 13 donors. In this communication, we show that the population of primed F1 T lymphocytes which can be activated by antigen-pulsed strain 2 PECs is largely independent of the population of cells that can be activated by antigen-pulsed strain 13 PECs. This was demonstrated by both positive and negative selection procedures. In the former, T lymphocytes from OVA-primed (2 x 13)F1 donors were enriched by initial culture with OVA-pulsed strain 2 or strain 13 PECs for 1 wk. Cells selected by culture with OVA-pulsed strain 2 PECs responded well to OVA-pulsed strain 2 PECs and poorly to OVA-pulsed strain 13 PECs. If positive selection had been carried out with OVA-pulsed strain 13 PECs, the selected F1 T cells responded well to OVA-pulsed 13 PECs and poorly to OVA-pulsed 2 PECs. Negative selection was achieved by short term culture with antigen-pulsed PECs and by eliminating proliferating cells by treatment with bromodeoxyuridine and light. This procedure demonstrated that the population of primed F1 T lymphocytes which are responsive to OVA or to purified protein derivative of tuberculin can be divided into subpopulations uniquely responsive to antigen on either strain 2 or strain 13 PECs. Evidence was presented to indicate that this selective responsiveness was not the result of the action of alloantigen-specific suppressor cells. The results are considered in terms of current concepts of the genetic and molecular regulation of the interaction of PECs and T lymphocytes.", "contents": "Independent populations of primed F1 guinea pig T lymphocytes respond to antigen-pulsed parental peritoneal exudate cells. Thymus-dependent (T) lymphocytes from (2 x 13)F1 hybrid guinea pigs immunized to ovalbumin (OVA) in complete Freund's adjuvant can be stimulated to proliferate in vitro by antigen-pulsed peritoneal exudate cells (PECs) derived from either strain 2 or strain 13 donors. In this communication, we show that the population of primed F1 T lymphocytes which can be activated by antigen-pulsed strain 2 PECs is largely independent of the population of cells that can be activated by antigen-pulsed strain 13 PECs. This was demonstrated by both positive and negative selection procedures. In the former, T lymphocytes from OVA-primed (2 x 13)F1 donors were enriched by initial culture with OVA-pulsed strain 2 or strain 13 PECs for 1 wk. Cells selected by culture with OVA-pulsed strain 2 PECs responded well to OVA-pulsed strain 2 PECs and poorly to OVA-pulsed strain 13 PECs. If positive selection had been carried out with OVA-pulsed strain 13 PECs, the selected F1 T cells responded well to OVA-pulsed 13 PECs and poorly to OVA-pulsed 2 PECs. Negative selection was achieved by short term culture with antigen-pulsed PECs and by eliminating proliferating cells by treatment with bromodeoxyuridine and light. This procedure demonstrated that the population of primed F1 T lymphocytes which are responsive to OVA or to purified protein derivative of tuberculin can be divided into subpopulations uniquely responsive to antigen on either strain 2 or strain 13 PECs. Evidence was presented to indicate that this selective responsiveness was not the result of the action of alloantigen-specific suppressor cells. The results are considered in terms of current concepts of the genetic and molecular regulation of the interaction of PECs and T lymphocytes."}
{"id": "PMID:233907", "title": "Experimental conditions for obtaining suppressor and helper effects on the primary in vitro immune response by lymphocytes activated by polyclonal T-cell activators.", "content": "The effect of the polyclonal T-cell activators (PTA) Con A and PHA on the specific immune response to sheep red blood cells (SRC) was studied. Addition of PTA either enhanced or suppressed the anti-SRC response, and two variables were found to affect the results: time of addition of the PTA and the strength of the response in control cultures not given PTA. If the response was high, even suboptimal PTA concentrations induced suppressive effects, but if the control response was low, due to deficient batches of sera or because of the absence of serum, the addition of PTA increased the response or restored it to normal levels. Suppression could be obtained if the PTA were added before or at the same time as the antigen and required high (optimal) PTA concentrations. If addition was delayed for 12-24 h the suppressive effects disappeared and previously suppressive concentrations of the PTA now caused an enhanced response. Analogous results were obtained if preactivated lymphocytes were added to the cultures instead of soluble PTA. Neither Con A, PHA, or lymphocytes preactivated by these PTA suppressed the polyclonal response induced by LPS or PPD. Irrespective of the time of addition and the culture conditions, enhancement of the anti-SRC response occurred at lower PTA concentrations than suppression. It was concluded that suppressor T cells, if they exist, do not act on B cells, but rather on helper cells needed for induction of thymus-dependent responses. The findings in this system are not compatible with the existence of a specific subset of suppressor T cells, but rather with the notion that suppression is caused by too much help.", "contents": "Experimental conditions for obtaining suppressor and helper effects on the primary in vitro immune response by lymphocytes activated by polyclonal T-cell activators. The effect of the polyclonal T-cell activators (PTA) Con A and PHA on the specific immune response to sheep red blood cells (SRC) was studied. Addition of PTA either enhanced or suppressed the anti-SRC response, and two variables were found to affect the results: time of addition of the PTA and the strength of the response in control cultures not given PTA. If the response was high, even suboptimal PTA concentrations induced suppressive effects, but if the control response was low, due to deficient batches of sera or because of the absence of serum, the addition of PTA increased the response or restored it to normal levels. Suppression could be obtained if the PTA were added before or at the same time as the antigen and required high (optimal) PTA concentrations. If addition was delayed for 12-24 h the suppressive effects disappeared and previously suppressive concentrations of the PTA now caused an enhanced response. Analogous results were obtained if preactivated lymphocytes were added to the cultures instead of soluble PTA. Neither Con A, PHA, or lymphocytes preactivated by these PTA suppressed the polyclonal response induced by LPS or PPD. Irrespective of the time of addition and the culture conditions, enhancement of the anti-SRC response occurred at lower PTA concentrations than suppression. It was concluded that suppressor T cells, if they exist, do not act on B cells, but rather on helper cells needed for induction of thymus-dependent responses. The findings in this system are not compatible with the existence of a specific subset of suppressor T cells, but rather with the notion that suppression is caused by too much help."}
{"id": "PMID:233908", "title": "Antiviral protection by virus-immune cytotoxic T cells: infected target cells are lysed before infectious virus progeny is assembled.", "content": "Virus-immune cytotoxic T cells can inhibit effectively growth of vaccinia virus in acutely infected target cells in vitro by destroying infected target cells before infectious virus progeny is assembled. Together with the fact that virus-specific T cells are demonstrable after 3 days, very early during infection, and with strong circumstantial evidence from adoptive transfer models in vivo, these data suggest that in some virus infections T cells may in fact act cytolytically in vivo to prevent virus growth and spread and be an important early antiviral effector mechanism.", "contents": "Antiviral protection by virus-immune cytotoxic T cells: infected target cells are lysed before infectious virus progeny is assembled. Virus-immune cytotoxic T cells can inhibit effectively growth of vaccinia virus in acutely infected target cells in vitro by destroying infected target cells before infectious virus progeny is assembled. Together with the fact that virus-specific T cells are demonstrable after 3 days, very early during infection, and with strong circumstantial evidence from adoptive transfer models in vivo, these data suggest that in some virus infections T cells may in fact act cytolytically in vivo to prevent virus growth and spread and be an important early antiviral effector mechanism."}
{"id": "PMID:233909", "title": "Generation of T-helper cells in vitro. I. Cellular and antigen requirements.", "content": "A sequential mouse cell culture system is described for the induction and assay of T-helper cells. Unprimed, cortisone-resistant, nylon wool-purified thymocytes cultured with adherent peritoneal exudate cells can be primed in vitro with soluble carrier protein to generate carrier-reactive helper cells. These cultured cells enhance the anti-hapten plaque-forming response of hapten-primed spleen cell cultures to hapten carrier conjugates. The culture conditions, cellular manipulations, and antigen requirements for the optimal induction of helper cells with these purified cell populations is presented. The active helper cell generated in this culture system is a thymus-derived cell which requires macrophages for its induction and must be proliferate in vitro before the manifestation of helper-cell function. Helper cells generated in vitro stimulate both carrier-specific and nonspecific enhancement of splenic anti-hapten responses. The carrier-specific and nonspecific enhancement can be distinguished by the requirement for antigen in the helper cell and spleen cell cultures, the dose of helper cells added to the spleen cell cultures, and by the requirement for additional splenic adherent accessory cell interactions.", "contents": "Generation of T-helper cells in vitro. I. Cellular and antigen requirements. A sequential mouse cell culture system is described for the induction and assay of T-helper cells. Unprimed, cortisone-resistant, nylon wool-purified thymocytes cultured with adherent peritoneal exudate cells can be primed in vitro with soluble carrier protein to generate carrier-reactive helper cells. These cultured cells enhance the anti-hapten plaque-forming response of hapten-primed spleen cell cultures to hapten carrier conjugates. The culture conditions, cellular manipulations, and antigen requirements for the optimal induction of helper cells with these purified cell populations is presented. The active helper cell generated in this culture system is a thymus-derived cell which requires macrophages for its induction and must be proliferate in vitro before the manifestation of helper-cell function. Helper cells generated in vitro stimulate both carrier-specific and nonspecific enhancement of splenic anti-hapten responses. The carrier-specific and nonspecific enhancement can be distinguished by the requirement for antigen in the helper cell and spleen cell cultures, the dose of helper cells added to the spleen cell cultures, and by the requirement for additional splenic adherent accessory cell interactions."}
{"id": "PMID:233910", "title": "A requirement for antigen-specific helper T cells in the generation of cytotoxic T cells from thymocyte precursors.", "content": "Thymocytes cultured with irradiated, allogeneic stimulator cells yield no cytotoxic effector cells after a period in culture. If, however, a population of irradiated spleen cells syngeneic to the responder cells are added to these cultures, cytotoxicity is generated. The helper activity present in the irradiated syngeneic spleen cells was found to be mediated by a cell bearing theta antigens. Furthermore, it was found to be antigen specific; helper cells which were tolerant of the stimulator cell antigens were unable to help the thymocyte responder cells, although these tolerant cells did contain helpers specific for a third party antigen. These experiments are consistent with a requirement for associative recognition of linked determinants in the induction of killer precursors which is thus strictly analogous to the induction of B-cell precursors via collaboration with helper T cells. In more extensive studies, it was found that histoincompatible helper cells (H-2b, H-2p, H-2q) were able to help a cytotoxic T cell (H-2k) response to a third party stimulator cell antigen (H-2d); that is, the helper T cells which interact with cytotoxic T-cell precursors are not strain specific. It seems likely that the histocompatible helper cells induce killer precursors in an antigen-specific cooperation event similar or identical to normal syngeneic cooperation.", "contents": "A requirement for antigen-specific helper T cells in the generation of cytotoxic T cells from thymocyte precursors. Thymocytes cultured with irradiated, allogeneic stimulator cells yield no cytotoxic effector cells after a period in culture. If, however, a population of irradiated spleen cells syngeneic to the responder cells are added to these cultures, cytotoxicity is generated. The helper activity present in the irradiated syngeneic spleen cells was found to be mediated by a cell bearing theta antigens. Furthermore, it was found to be antigen specific; helper cells which were tolerant of the stimulator cell antigens were unable to help the thymocyte responder cells, although these tolerant cells did contain helpers specific for a third party antigen. These experiments are consistent with a requirement for associative recognition of linked determinants in the induction of killer precursors which is thus strictly analogous to the induction of B-cell precursors via collaboration with helper T cells. In more extensive studies, it was found that histoincompatible helper cells (H-2b, H-2p, H-2q) were able to help a cytotoxic T cell (H-2k) response to a third party stimulator cell antigen (H-2d); that is, the helper T cells which interact with cytotoxic T-cell precursors are not strain specific. It seems likely that the histocompatible helper cells induce killer precursors in an antigen-specific cooperation event similar or identical to normal syngeneic cooperation."}
{"id": "PMID:233911", "title": "Prevention of IgG2a production as a result of allotype-specific interaction between T and B cells.", "content": "BALB/c T cells, which can prevent normal C57BL IgG2a allotype (G2) production of Ig-congenic partner mice (C.B mice), are shown capable of preventing the growth and G2 production of a C.B plasmacytoma (CBPC 101). Such cytotoxic or suppressor T cells are clearly allotype-specific (G2 Tcs cells). And since CBPC 101 B cells do not require specific helper T cells in order to grow, we infer that G2-bearing B cells (normal or neoplastic) must be the direct target of G2 Tcs cells. This mode of T cell prevention of allotype production contrasts that reported for suppressor T cells in (BALB/c x SJL)F1 mice.", "contents": "Prevention of IgG2a production as a result of allotype-specific interaction between T and B cells. BALB/c T cells, which can prevent normal C57BL IgG2a allotype (G2) production of Ig-congenic partner mice (C.B mice), are shown capable of preventing the growth and G2 production of a C.B plasmacytoma (CBPC 101). Such cytotoxic or suppressor T cells are clearly allotype-specific (G2 Tcs cells). And since CBPC 101 B cells do not require specific helper T cells in order to grow, we infer that G2-bearing B cells (normal or neoplastic) must be the direct target of G2 Tcs cells. This mode of T cell prevention of allotype production contrasts that reported for suppressor T cells in (BALB/c x SJL)F1 mice."}
{"id": "PMID:233912", "title": "DNA-binding property of Sm nuclear antigen.", "content": "Antibodies in the sera of patients with systemic lupus erythematosus reacted with a nuclear acidic protein called Sm antigen, and these antibodies were used as reagents to identify Sm antigen in preparative fractionation procedures. DNA affinity chromatography showed that Sm antigen was associated with nuclear protein fractions which had DNA-binding capacity. Evidence was also presented that Sm antigen showed preferential binding for single-strand DNA over double-strand DNA. These studies demonstrate that spontaneously occurring anti-nuclear antibodies in disease states may be used to study the properties of cellular proteins which are present in trace amounts.", "contents": "DNA-binding property of Sm nuclear antigen. Antibodies in the sera of patients with systemic lupus erythematosus reacted with a nuclear acidic protein called Sm antigen, and these antibodies were used as reagents to identify Sm antigen in preparative fractionation procedures. DNA affinity chromatography showed that Sm antigen was associated with nuclear protein fractions which had DNA-binding capacity. Evidence was also presented that Sm antigen showed preferential binding for single-strand DNA over double-strand DNA. These studies demonstrate that spontaneously occurring anti-nuclear antibodies in disease states may be used to study the properties of cellular proteins which are present in trace amounts."}
{"id": "PMID:233913", "title": "Eosinophils and resistance to Trichinella spiralis.", "content": "Mice infected with Trichinella spiralis were depleted of eosinophils by repeated administration of rabbit anti-mouse eosinophil serum. There was no effect on the spontaneous expulsion of adult worms from the small intestines, but the numbers of larvae in the muscles were almost doubled. It is concluded that eosinophils contribute to resistance to the systemic phase of trichinosis.", "contents": "Eosinophils and resistance to Trichinella spiralis. Mice infected with Trichinella spiralis were depleted of eosinophils by repeated administration of rabbit anti-mouse eosinophil serum. There was no effect on the spontaneous expulsion of adult worms from the small intestines, but the numbers of larvae in the muscles were almost doubled. It is concluded that eosinophils contribute to resistance to the systemic phase of trichinosis."}
{"id": "PMID:233914", "title": "Parallel synthesis of immunoglobulins and J chain in pokeweed mitogen-stimulated normal cells and in lymphoblastoid cell lines.", "content": "The synthesis of intracellular J chains was found to be closely associated with that of intracellular immunoglobulin, regardless of its class, during the process of B-cell differentiation. This parallelism between the synthesis of J chain and immunoglobulin was particularly evident in their coincident appearance in serial observations of pokeweed mitogen (PWM)-stimulated lymphocytes. The intensity of J-chain staining by fluorescent reagents in the stimulated cells synthesizing IgG was similar to that found in cells synthesizing IgA or IgM. Evidence was obtained that the presence of J chain in the IgG-producing cells did not reflect antecedent synthesis of IgA or IgM. T cells stimulated by phytohemagglutinin and PWM failed to show J-chain synthesis. Observations on lymphoid cell lines showed a similar parallelism between intracellular Ig and J-chain synthesis; no relation to surface Ig was found.", "contents": "Parallel synthesis of immunoglobulins and J chain in pokeweed mitogen-stimulated normal cells and in lymphoblastoid cell lines. The synthesis of intracellular J chains was found to be closely associated with that of intracellular immunoglobulin, regardless of its class, during the process of B-cell differentiation. This parallelism between the synthesis of J chain and immunoglobulin was particularly evident in their coincident appearance in serial observations of pokeweed mitogen (PWM)-stimulated lymphocytes. The intensity of J-chain staining by fluorescent reagents in the stimulated cells synthesizing IgG was similar to that found in cells synthesizing IgA or IgM. Evidence was obtained that the presence of J chain in the IgG-producing cells did not reflect antecedent synthesis of IgA or IgM. T cells stimulated by phytohemagglutinin and PWM failed to show J-chain synthesis. Observations on lymphoid cell lines showed a similar parallelism between intracellular Ig and J-chain synthesis; no relation to surface Ig was found."}
{"id": "PMID:233915", "title": "The immune response of allophenic mice to the synthetic polymer L-glutamic acid, L-lysine, L-phenylalanine. II. Lack of gene complementation in two nonresponder strains.", "content": "The genetic control of the immune response of inbred strains of mice to certain antigens has been demonstrated to be governed by a set of Ir genes linked to the major histocompatibility complex (H-2) of mice (1,2). Until recently, the control was thought to be governed by single, dominant genes, located within the I region of the H-2 complex. Merryman et al. (3) originally demonstrated that the immune response to the synthetic terpolymer L-glutamic acid, L-lysine, L-phenylaline (GLphi) is under dominant, H-2-linked Ir gene control (4-7). This was shown both by crossing two nonresponder parental strains to produce responder offspring in the F(1) generation, and by the analysis of appropriate recombinant stains of mice. The two complementing genes have been mapped in the IA and IC regions of the H-2 complex, and have been termed beta and alpha, respectively (5,6). Thus, any strain of mouse may contain neither, one, or both genes. Only mice containing both genes are capable of responding to GLphi. It has been shown using F(1) hybrid and recombinant strains of mice, that the alpha- and beta-genes can complement each other in either the cis (on the same chromosome) or in the trans (on different chromosomes) position (8). In this paper we report the results of studies aimed at answering the question of whether or not the alpha- and beta- genes can complement each other when they are present in different lymphoid cells. To this end we have constructed allophenic mice composed of two nonresponder strains (A and C57BL/6), which show gene complementation in the F(1) generation. Allophenic mice are chimeras containing two cell types coexisting in a \"normal\" environment. The mice were tested for the specific cellular composition of the two parental cell types and were found to possess a complete range in the relative proportion of the two cell types. This report demonstrates that regardless of the mixture of cell types present in the allophenic mice, none of them were responders to GLphi. Thus no complementation of the alpha- and beta-genes is seen when the two genes are present in different cells.", "contents": "The immune response of allophenic mice to the synthetic polymer L-glutamic acid, L-lysine, L-phenylalanine. II. Lack of gene complementation in two nonresponder strains. The genetic control of the immune response of inbred strains of mice to certain antigens has been demonstrated to be governed by a set of Ir genes linked to the major histocompatibility complex (H-2) of mice (1,2). Until recently, the control was thought to be governed by single, dominant genes, located within the I region of the H-2 complex. Merryman et al. (3) originally demonstrated that the immune response to the synthetic terpolymer L-glutamic acid, L-lysine, L-phenylaline (GLphi) is under dominant, H-2-linked Ir gene control (4-7). This was shown both by crossing two nonresponder parental strains to produce responder offspring in the F(1) generation, and by the analysis of appropriate recombinant stains of mice. The two complementing genes have been mapped in the IA and IC regions of the H-2 complex, and have been termed beta and alpha, respectively (5,6). Thus, any strain of mouse may contain neither, one, or both genes. Only mice containing both genes are capable of responding to GLphi. It has been shown using F(1) hybrid and recombinant strains of mice, that the alpha- and beta-genes can complement each other in either the cis (on the same chromosome) or in the trans (on different chromosomes) position (8). In this paper we report the results of studies aimed at answering the question of whether or not the alpha- and beta- genes can complement each other when they are present in different lymphoid cells. To this end we have constructed allophenic mice composed of two nonresponder strains (A and C57BL/6), which show gene complementation in the F(1) generation. Allophenic mice are chimeras containing two cell types coexisting in a \"normal\" environment. The mice were tested for the specific cellular composition of the two parental cell types and were found to possess a complete range in the relative proportion of the two cell types. This report demonstrates that regardless of the mixture of cell types present in the allophenic mice, none of them were responders to GLphi. Thus no complementation of the alpha- and beta-genes is seen when the two genes are present in different cells."}
{"id": "PMID:233916", "title": "Transplacental influence of the thymus.", "content": "Peripheral blood lymphocyte levels attained in adult rats that had been thymectomized at birth were markedly reduced if the two or three immediately preceding generations of rats from which they were bred had been thymectomized as neonates. The capacity of thymectomized animals to survive to adult life was also drastically reduced if they were bred from thymectomized stock. Pregnancy as a result of mating with syngeneic or allogeneic males produced an ephemeral increase in peripheral blood lymphocyte levels of third and fourth generation thymectomized females. These observations are most readily explicable on the basis of a thymus-derived humoral influence acting directly or indirectly to influence the circulating lymphocyte population.", "contents": "Transplacental influence of the thymus. Peripheral blood lymphocyte levels attained in adult rats that had been thymectomized at birth were markedly reduced if the two or three immediately preceding generations of rats from which they were bred had been thymectomized as neonates. The capacity of thymectomized animals to survive to adult life was also drastically reduced if they were bred from thymectomized stock. Pregnancy as a result of mating with syngeneic or allogeneic males produced an ephemeral increase in peripheral blood lymphocyte levels of third and fourth generation thymectomized females. These observations are most readily explicable on the basis of a thymus-derived humoral influence acting directly or indirectly to influence the circulating lymphocyte population."}
{"id": "PMID:233917", "title": "Cell surface antigens of human malignant melanoma. III. Recognition of autoantibodies with unusual characteristics.", "content": "The sera of three patients with malignant melanoma showing reactivity with surface antigens of cultured autologous melanoma cells were analyzed by mixed hemadsorption and immune adherence assays in conjunction with absorption tests. In contrast to the melanoma-specific antigens demonstrated previously, the surface antigens detected by these sera occurred on a broad range of nucleated cells, both normal and malignant, from human, monkey, mouse, and chicken sources. Each serum had a characteristic pattern of reactivity in absorption tests, indicating the detection of distinct antigenic systems. Two sera showed auto-, allo-, and xenoreactivity, as well as the capacity to distinguish different cell populations in the same individual. The other serum reacted with an antigen apparently universally present on nucleated cells from a variety of species, but absent on erythrocytes. As these patients had been treated with chemotherapy, this may have played a role in the emergence of these broadly reactive autoantibodies.", "contents": "Cell surface antigens of human malignant melanoma. III. Recognition of autoantibodies with unusual characteristics. The sera of three patients with malignant melanoma showing reactivity with surface antigens of cultured autologous melanoma cells were analyzed by mixed hemadsorption and immune adherence assays in conjunction with absorption tests. In contrast to the melanoma-specific antigens demonstrated previously, the surface antigens detected by these sera occurred on a broad range of nucleated cells, both normal and malignant, from human, monkey, mouse, and chicken sources. Each serum had a characteristic pattern of reactivity in absorption tests, indicating the detection of distinct antigenic systems. Two sera showed auto-, allo-, and xenoreactivity, as well as the capacity to distinguish different cell populations in the same individual. The other serum reacted with an antigen apparently universally present on nucleated cells from a variety of species, but absent on erythrocytes. As these patients had been treated with chemotherapy, this may have played a role in the emergence of these broadly reactive autoantibodies."}
{"id": "PMID:233918", "title": "Joint recognition by cytotoxic T cells of inactivated Sendai virus and products of the major histocompatibility complex.", "content": "Cytotoxic T cells specific for Sendai virus were generated by culturing murine spleen cells in vitro together with UV-inactivated Sendai virus. In vivo immunization of donor mice with UV-inactivated Sendai virus resulted in an in vitro secondary response of increased magnitude. Cytotoxic activity was demonstrated in a short-term 51Cr-release assay, using syngeneic tumor cells which had been coated with inactivated Sendai virus by incubation at 4 degrees C for 30 min. The lysis of Sendai virus-coated target cells was restricted by the H-2 haplotype of the target cells, suggesting that the H-2 genes of the target cell contributed to the specificity of the lysis. Kinetic experiments showed that susceptibility to lysis by cytotoxic T cells specific for Sendai virus appeared within 30 min after coating target cells with inactivated virus. Furthermore, there was no detectable synthesis of new proteins in cells treated with UV-inactivated Sendai virus. For these reasons, we suggest that neither viral replication nor the synthesis of new proteins are necessary for the production of the antigen recognized by cytotoxic cells specific for Sendai virus. We infer that the virus-specific component on the target cells is probably a preformed virion antigen adsorbed onto or integrated into the cell membrane. These results imply that, if the cytotoxic T cell recognizes a single antigenic determinant specified both by viral and H-2 genes, this determinant is formed by the physical association of H-2 and Sendai virus antigens rather than by their alteration during the processes of synthesis.", "contents": "Joint recognition by cytotoxic T cells of inactivated Sendai virus and products of the major histocompatibility complex. Cytotoxic T cells specific for Sendai virus were generated by culturing murine spleen cells in vitro together with UV-inactivated Sendai virus. In vivo immunization of donor mice with UV-inactivated Sendai virus resulted in an in vitro secondary response of increased magnitude. Cytotoxic activity was demonstrated in a short-term 51Cr-release assay, using syngeneic tumor cells which had been coated with inactivated Sendai virus by incubation at 4 degrees C for 30 min. The lysis of Sendai virus-coated target cells was restricted by the H-2 haplotype of the target cells, suggesting that the H-2 genes of the target cell contributed to the specificity of the lysis. Kinetic experiments showed that susceptibility to lysis by cytotoxic T cells specific for Sendai virus appeared within 30 min after coating target cells with inactivated virus. Furthermore, there was no detectable synthesis of new proteins in cells treated with UV-inactivated Sendai virus. For these reasons, we suggest that neither viral replication nor the synthesis of new proteins are necessary for the production of the antigen recognized by cytotoxic cells specific for Sendai virus. We infer that the virus-specific component on the target cells is probably a preformed virion antigen adsorbed onto or integrated into the cell membrane. These results imply that, if the cytotoxic T cell recognizes a single antigenic determinant specified both by viral and H-2 genes, this determinant is formed by the physical association of H-2 and Sendai virus antigens rather than by their alteration during the processes of synthesis."}
{"id": "PMID:233919", "title": "Surface properties related to concanavalin A-induced agglutination. A comparative study of several Entamoeba strains.", "content": "Pathogenic strains of Entamoeba histolytica are more easily agglutinated with concanavalin A (Con A) than strains isolated from human asymptomatic carriers. All three pathogenic strains studied here were found to agglutinate with low concentrations of Con A in contrast to various nonpathogenic axenic strains of amebas, characterized by their ability to grow at room temperature. Our present observations suggest that the extreme susceptibility of pathogenic strains of E. histolytica to agglutinate with Con A is related to their higher capacity for lectin binding and to their lack of detectable repulsive charges at the cell surface. The amount of fluorescein-tagged Con A bound to the surface was much higher in pathogenic strains. Only nonpathogenic strains showed a detectable negative surface charge as studied both by means of cell microelectrophoresis and by labeling cells with cationized ferritin at 0 degrees C. The mobility of surface Con A receptors estimated as the percentage of caps was comparable in all strains. Results of one strain cultured in axenic and monoxenic conditions suggested that bacteria can modify the behaviour of E. histolytica trophozoites by altering surface properties of the amebas.", "contents": "Surface properties related to concanavalin A-induced agglutination. A comparative study of several Entamoeba strains. Pathogenic strains of Entamoeba histolytica are more easily agglutinated with concanavalin A (Con A) than strains isolated from human asymptomatic carriers. All three pathogenic strains studied here were found to agglutinate with low concentrations of Con A in contrast to various nonpathogenic axenic strains of amebas, characterized by their ability to grow at room temperature. Our present observations suggest that the extreme susceptibility of pathogenic strains of E. histolytica to agglutinate with Con A is related to their higher capacity for lectin binding and to their lack of detectable repulsive charges at the cell surface. The amount of fluorescein-tagged Con A bound to the surface was much higher in pathogenic strains. Only nonpathogenic strains showed a detectable negative surface charge as studied both by means of cell microelectrophoresis and by labeling cells with cationized ferritin at 0 degrees C. The mobility of surface Con A receptors estimated as the percentage of caps was comparable in all strains. Results of one strain cultured in axenic and monoxenic conditions suggested that bacteria can modify the behaviour of E. histolytica trophozoites by altering surface properties of the amebas."}
{"id": "PMID:233920", "title": "Generation of T-helper cells in vitro. II. Analysis of supernates derived from T-helper cell cultures.", "content": "Supernates derived from in vitro generated T-helper cells have been analyzed for their capacity to substitute for T-cell carrier reactivity. T-helper cell supernates stimulate both a carrier-specific and nonspecific anti-DNP-PFC response to DNP-carrier conjugates in cultures of hapten-primed spleen cells. The carrier-specific and nonspecific activity can be distinguished by dosage optimum, antigen requirements, binding specificity for carrier, and in the requirement for additional splenic adherent accessory cell involvement. The active factors produced in this system are heat labile and sensitive to trypsin and periodate. They are removed by absorption with alloantisera directed toward the strain from which the supernate was derived but not by a variety of anti-immunoglobulin sera.", "contents": "Generation of T-helper cells in vitro. II. Analysis of supernates derived from T-helper cell cultures. Supernates derived from in vitro generated T-helper cells have been analyzed for their capacity to substitute for T-cell carrier reactivity. T-helper cell supernates stimulate both a carrier-specific and nonspecific anti-DNP-PFC response to DNP-carrier conjugates in cultures of hapten-primed spleen cells. The carrier-specific and nonspecific activity can be distinguished by dosage optimum, antigen requirements, binding specificity for carrier, and in the requirement for additional splenic adherent accessory cell involvement. The active factors produced in this system are heat labile and sensitive to trypsin and periodate. They are removed by absorption with alloantisera directed toward the strain from which the supernate was derived but not by a variety of anti-immunoglobulin sera."}
{"id": "PMID:233923", "title": "A rapid method, using octadecasilyl-silica, for the extraction of certain peptides from tissues.", "content": "Peptides can be recovered from tissues by homogenization in a carefully selected extraction medium followed by adsorption from the supernatant on a small bed of octadecasilyl-silica. Recoveries of corticotropins and somatostatin added to a variety of tissues were quantitative, and the peptides undamaged as determined by high-pressure liquid chromatography.", "contents": "A rapid method, using octadecasilyl-silica, for the extraction of certain peptides from tissues. Peptides can be recovered from tissues by homogenization in a carefully selected extraction medium followed by adsorption from the supernatant on a small bed of octadecasilyl-silica. Recoveries of corticotropins and somatostatin added to a variety of tissues were quantitative, and the peptides undamaged as determined by high-pressure liquid chromatography."}
{"id": "PMID:233925", "title": "Regeneration of the renal calyces after calycectomy: an experimental study.", "content": "On 14 rabbits, 21 kidneys were subjected to a calycectomy or the tip of the papilla was cut off by caudal nephrotomy. During an observation period of 2, 4, 6, 8 and 10 days, and further after 3 and 6 weeks the macroscopic and microscopic investigations led to the following results clearly answering the question put at the beginning of the inquiry: (1) even if parts of the renal calyces are removed, a complete regeneration of the renal pelvic mucosa takes place in the damaged area; (2) regeneration of the mucosa begins in neighbouring renal pelvic epithelium and the epithelium of the collecting tubes; (3) regeneration starts on the 4th day and is essentially ended by the 3rd week; this regeneration extends over the whole of the injured area; after the 6th week the process is finished and no inflammatory changes are to be found in the damaged area, and (4) in the process of healing no fibrous tissue is formed at the occlusion of the lamina cribrosa in the area of the papilla; there is no demonstrable necrosis of the renal parenchyma where the mucosa was removed. Hydronephrosis in this area is evident, beginning on the 3rd or 4th day and is to be regarded as the result of inflammatory process or of the operation itself. It is partly in evidence after 6 weeks but is clearly in a regressive stage. Morphologically a functional loss of the affected area of renal tissue cannot be demonstrated. The four questions made and answered by this animal experiment allow the following conclusion: calycectomy can be successfully undertaken. Regeneration of the mucosa is almost finished after 3 weeks and finally completed after 6 weeks. Considerable cicatrisation in the area of the mucous membrane injury or of its nephrons is morphologically unimportant. Calycectomy should be preferred to polar resection as there is a smaller parenchymal loss.", "contents": "Regeneration of the renal calyces after calycectomy: an experimental study. On 14 rabbits, 21 kidneys were subjected to a calycectomy or the tip of the papilla was cut off by caudal nephrotomy. During an observation period of 2, 4, 6, 8 and 10 days, and further after 3 and 6 weeks the macroscopic and microscopic investigations led to the following results clearly answering the question put at the beginning of the inquiry: (1) even if parts of the renal calyces are removed, a complete regeneration of the renal pelvic mucosa takes place in the damaged area; (2) regeneration of the mucosa begins in neighbouring renal pelvic epithelium and the epithelium of the collecting tubes; (3) regeneration starts on the 4th day and is essentially ended by the 3rd week; this regeneration extends over the whole of the injured area; after the 6th week the process is finished and no inflammatory changes are to be found in the damaged area, and (4) in the process of healing no fibrous tissue is formed at the occlusion of the lamina cribrosa in the area of the papilla; there is no demonstrable necrosis of the renal parenchyma where the mucosa was removed. Hydronephrosis in this area is evident, beginning on the 3rd or 4th day and is to be regarded as the result of inflammatory process or of the operation itself. It is partly in evidence after 6 weeks but is clearly in a regressive stage. Morphologically a functional loss of the affected area of renal tissue cannot be demonstrated. The four questions made and answered by this animal experiment allow the following conclusion: calycectomy can be successfully undertaken. Regeneration of the mucosa is almost finished after 3 weeks and finally completed after 6 weeks. Considerable cicatrisation in the area of the mucous membrane injury or of its nephrons is morphologically unimportant. Calycectomy should be preferred to polar resection as there is a smaller parenchymal loss."}
{"id": "PMID:233922", "title": "Studies on the active principles of Schisandra sphenanthera Rehd. et Wils. The structures of schisantherin A, B, C, D, E, and the related compounds.", "content": "Deoxyschisandrin (VIII) and five new lignans, named schisantherin A, B, C, D, and E, were isolated from the active fraction of the fruits of Schisandra sphenanthera Rehd. et Wils. Their configurations and conformations were established by exhaustive spectral analysis as well as chemical degradations as shown in Ia, Ib; IIa, IIb; IIIa, IIIb; IVa, IVb, and Va, Vb respectively, and their absolute configurations at biphenyl, at C6, C7, and C8 were all assigned to be S form. The position of the methylenedioxyl group in the structures of gamma-schisandrin and Wuweizisu C (as described in the literature), isolated from Schisandra chinensis, must be corrected as shown in VI and VII respectively. In pharmacologica studies and preliminary clinical trials, schisantherin A, B, C, and D showed good effect in lowering the serum glutamic-pyruvic transaminase level of the patients suffering from chronic virus hepatitis. Schisantherin E and deoxyschisandrin were not effective.", "contents": "Studies on the active principles of Schisandra sphenanthera Rehd. et Wils. The structures of schisantherin A, B, C, D, E, and the related compounds. Deoxyschisandrin (VIII) and five new lignans, named schisantherin A, B, C, D, and E, were isolated from the active fraction of the fruits of Schisandra sphenanthera Rehd. et Wils. Their configurations and conformations were established by exhaustive spectral analysis as well as chemical degradations as shown in Ia, Ib; IIa, IIb; IIIa, IIIb; IVa, IVb, and Va, Vb respectively, and their absolute configurations at biphenyl, at C6, C7, and C8 were all assigned to be S form. The position of the methylenedioxyl group in the structures of gamma-schisandrin and Wuweizisu C (as described in the literature), isolated from Schisandra chinensis, must be corrected as shown in VI and VII respectively. In pharmacologica studies and preliminary clinical trials, schisantherin A, B, C, and D showed good effect in lowering the serum glutamic-pyruvic transaminase level of the patients suffering from chronic virus hepatitis. Schisantherin E and deoxyschisandrin were not effective."}
{"id": "PMID:233927", "title": "Primary hepatic pregnancy. Case report.", "content": "A case of primary hepatic pregnancy presenting as a lithopedion in the right hypochondrium is presented. The lithopedion was removed and the patient recovered uneventfully. The diagnosis of primary hepatic pregnancy is briefly discussed.", "contents": "Primary hepatic pregnancy. Case report. A case of primary hepatic pregnancy presenting as a lithopedion in the right hypochondrium is presented. The lithopedion was removed and the patient recovered uneventfully. The diagnosis of primary hepatic pregnancy is briefly discussed."}
{"id": "PMID:233929", "title": "Triage, education, and group meetings: efficient use of the interdisciplinary team with chronic psychiatric outpatients.", "content": "The caseload of chronic patients of a large mental health outpatient clinic was triaged into medication groups with educational and socialization emphasis. Organization, division of staff responsibilities, and longitudinal clinic responses are described, and advantages and pitfalls of the group format are presented.", "contents": "Triage, education, and group meetings: efficient use of the interdisciplinary team with chronic psychiatric outpatients. The caseload of chronic patients of a large mental health outpatient clinic was triaged into medication groups with educational and socialization emphasis. Organization, division of staff responsibilities, and longitudinal clinic responses are described, and advantages and pitfalls of the group format are presented."}
{"id": "PMID:233926", "title": "[Effect of stress on sleep characteristics in humans].", "content": "Earlier investigations of Baekeland et al. (1968) showed that stress conditions change the characteristic features of sleep. It was the aim of this work to compare the effect of pre-examination stress and preoperative stress on the characteristic features of sleep. Three groups of 5 individuals each were studied: students, patients and controls aged from 20 to 45 years. In all patients psychological investigations by the test of Cattel were carried out before each polygraphic recording. These investigations confirmed presence of anxiety prior to falling asleep in the groups of students and patients and its effect on the subsequent sleep. The most significant changes during stress were observed in paradoxical sleep (REM). The amount of this sleep is reduced during stress while its intensity increases significantly (phasic REM sleep period). Persistence of disturbances of sleep depends on the duration of stress stimulus. The stress reaction connected with examination was short-lasting and disappeared after passing the examination. In the group of patients the stress reaction was prolonged on the average 33 days after the operation.", "contents": "[Effect of stress on sleep characteristics in humans]. Earlier investigations of Baekeland et al. (1968) showed that stress conditions change the characteristic features of sleep. It was the aim of this work to compare the effect of pre-examination stress and preoperative stress on the characteristic features of sleep. Three groups of 5 individuals each were studied: students, patients and controls aged from 20 to 45 years. In all patients psychological investigations by the test of Cattel were carried out before each polygraphic recording. These investigations confirmed presence of anxiety prior to falling asleep in the groups of students and patients and its effect on the subsequent sleep. The most significant changes during stress were observed in paradoxical sleep (REM). The amount of this sleep is reduced during stress while its intensity increases significantly (phasic REM sleep period). Persistence of disturbances of sleep depends on the duration of stress stimulus. The stress reaction connected with examination was short-lasting and disappeared after passing the examination. In the group of patients the stress reaction was prolonged on the average 33 days after the operation."}
{"id": "PMID:233935", "title": "Acute and chronic estradiol-17beta inhibition of LH release in prepubertal female pigs: time course and site of action.", "content": "It has been demonstrated that 5.0 mug estradiol-17beta (E2) iv inhibits spontaneous episodic release (SER) of LH from 3-9 h after injection in immature female pigs (gilts). To understand this phenomenon we tested pituitary response (PR) to synthetic LH-RH/FSH-RH (LH-RH) for 13 h after identical E2 treatment in eight 7-8-week-old gilts. Using chronic cannulae PR was determined by measuring the change in plasma LH (delta LH) by RIA after iv injection of 2.0 mug LH-RH. PR was determined every 2 h starting 1 or 2 h before E2 or saline treatments. The PR prior to treatment was 4.3 plus or minus 0.3 ng/ml. By the second releasing-hormone challenge PR in controls was depressed, remaining at about 2.5 ng/ml thereafter. Compared with controls PR depression was greater (P less than 0.005) 1 h following E2 (delta LH = 1.0 plus or minus 0.4 ng/ml). Responsiveness then returned toward pretreatment levels and from 6 h post-treatment onward PR was not different from controls. Initial inhibition of SER may therefore be located in the pituitary and brain. However, after 4 h inhibition appears to be purely neural. Earlier studies showed that subcutaneous (SC) implants of E2 for 3 days in prepubertal gilts depressed PR to LH-RH. We further examined the effect upon PR of implants releasing physiologic levels of E2. PR was evaluated as above at 2-h intervals for 12 h after SC implantation of silastic capsules containing E2 (n = 6) or sham implant (n = 1); then every 6 h up to 54 h post-treatment. For the first 12 h PR depression in the control was identical to controls in the acute experiment; after 36 h PR was similar to pretreatment levels. In E2 implanted animals PR fell to a mean of 1.8 plus or minus 0.1 ng/ml, 4-12 h after implantation, then recovered, stabilizing at 2.3 plus or minus 0.1 ng/ml after 18 h. It is concluded that estrogen treatment rapidly causes a depression of pituitary response to exogenous LH-RH. This rapid effect may not be dependent on E2 dosage. The extent of recovery of pituitary responsiveness probably depends upon the level and persistence of the E2 treatment.", "contents": "Acute and chronic estradiol-17beta inhibition of LH release in prepubertal female pigs: time course and site of action. It has been demonstrated that 5.0 mug estradiol-17beta (E2) iv inhibits spontaneous episodic release (SER) of LH from 3-9 h after injection in immature female pigs (gilts). To understand this phenomenon we tested pituitary response (PR) to synthetic LH-RH/FSH-RH (LH-RH) for 13 h after identical E2 treatment in eight 7-8-week-old gilts. Using chronic cannulae PR was determined by measuring the change in plasma LH (delta LH) by RIA after iv injection of 2.0 mug LH-RH. PR was determined every 2 h starting 1 or 2 h before E2 or saline treatments. The PR prior to treatment was 4.3 plus or minus 0.3 ng/ml. By the second releasing-hormone challenge PR in controls was depressed, remaining at about 2.5 ng/ml thereafter. Compared with controls PR depression was greater (P less than 0.005) 1 h following E2 (delta LH = 1.0 plus or minus 0.4 ng/ml). Responsiveness then returned toward pretreatment levels and from 6 h post-treatment onward PR was not different from controls. Initial inhibition of SER may therefore be located in the pituitary and brain. However, after 4 h inhibition appears to be purely neural. Earlier studies showed that subcutaneous (SC) implants of E2 for 3 days in prepubertal gilts depressed PR to LH-RH. We further examined the effect upon PR of implants releasing physiologic levels of E2. PR was evaluated as above at 2-h intervals for 12 h after SC implantation of silastic capsules containing E2 (n = 6) or sham implant (n = 1); then every 6 h up to 54 h post-treatment. For the first 12 h PR depression in the control was identical to controls in the acute experiment; after 36 h PR was similar to pretreatment levels. In E2 implanted animals PR fell to a mean of 1.8 plus or minus 0.1 ng/ml, 4-12 h after implantation, then recovered, stabilizing at 2.3 plus or minus 0.1 ng/ml after 18 h. It is concluded that estrogen treatment rapidly causes a depression of pituitary response to exogenous LH-RH. This rapid effect may not be dependent on E2 dosage. The extent of recovery of pituitary responsiveness probably depends upon the level and persistence of the E2 treatment."}
{"id": "PMID:233937", "title": "Stimulation of Adenosine 3',5'-monophosphate formation in incubated rat hypothalamus by estrogenic compounds: relationship to biologic potency and blockade by anti-estrogens.", "content": "Several estrogenic compounds were examined for their abilities to stimulate the formation of adenosine 3',5'-monophosphate (cyclic AMP) in incubated hypothalami from immature (27-28 day old) female rats. 17-beta estradiol (E2) and diethylstilbestrol (DES) significantly increased the formation of cyclic AMP while estrone and estriol elicited small but not statistically significant increases in cyclic AMP formation. 17-alpha estradiol was ineffective in increasing cyclic AMP formation. The anti-estrogenic agent clomiphene was found to effectively antagonize the formation of cyclic AMP elicited by E2 and DES, while having no stimulatory effects  on cyclic AMP formation itself. These data indicate that the binding of estrogenic compounds to cytoplasmic sites (receptors) in the hypothalamus is required for subsequent stimulation of cyclic AMP formations.", "contents": "Stimulation of Adenosine 3',5'-monophosphate formation in incubated rat hypothalamus by estrogenic compounds: relationship to biologic potency and blockade by anti-estrogens. Several estrogenic compounds were examined for their abilities to stimulate the formation of adenosine 3',5'-monophosphate (cyclic AMP) in incubated hypothalami from immature (27-28 day old) female rats. 17-beta estradiol (E2) and diethylstilbestrol (DES) significantly increased the formation of cyclic AMP while estrone and estriol elicited small but not statistically significant increases in cyclic AMP formation. 17-alpha estradiol was ineffective in increasing cyclic AMP formation. The anti-estrogenic agent clomiphene was found to effectively antagonize the formation of cyclic AMP elicited by E2 and DES, while having no stimulatory effects  on cyclic AMP formation itself. These data indicate that the binding of estrogenic compounds to cytoplasmic sites (receptors) in the hypothalamus is required for subsequent stimulation of cyclic AMP formations."}
{"id": "PMID:233938", "title": "Inflammatory fibrous polyp (pseudotumor) of ileum, a rare cause of intestinal obstruction.", "content": "Inflammatory fibrous polyp of the ileum is a rare condition. This report adds one patient to the 11 previously reported. These lesions usually involve intermittent, colicky abdominal pain, often of several weeks duration and occasionally as a cause of acute intestinal obstruction. X-rays usually show small bowel obstruction or intussusception, but may be completely normal. The pathological diagnosis is seldom made before microscopic examination of resected specimens. They are clinically interpreted to be neoplasm and treated by segmental resection. No recurrences have been reported after treatment. Etiology is unknown.", "contents": "Inflammatory fibrous polyp (pseudotumor) of ileum, a rare cause of intestinal obstruction. Inflammatory fibrous polyp of the ileum is a rare condition. This report adds one patient to the 11 previously reported. These lesions usually involve intermittent, colicky abdominal pain, often of several weeks duration and occasionally as a cause of acute intestinal obstruction. X-rays usually show small bowel obstruction or intussusception, but may be completely normal. The pathological diagnosis is seldom made before microscopic examination of resected specimens. They are clinically interpreted to be neoplasm and treated by segmental resection. No recurrences have been reported after treatment. Etiology is unknown."}
{"id": "PMID:233940", "title": "Obstructing polyps of the posterior urethra in boys: embryology and management.", "content": "Solitary fibrous polyps are in uncommon but important cause of obstructive uropathy, infection and hematuria in boys. The clinical presentation and management in 5 boys are discussed and the literature is reviewed. Emphasis is placed on the pitfalls in diagnosis and recent endoscopic techniques of treatment.", "contents": "Obstructing polyps of the posterior urethra in boys: embryology and management. Solitary fibrous polyps are in uncommon but important cause of obstructive uropathy, infection and hematuria in boys. The clinical presentation and management in 5 boys are discussed and the literature is reviewed. Emphasis is placed on the pitfalls in diagnosis and recent endoscopic techniques of treatment."}
{"id": "PMID:233941", "title": "Stabilization and purification of glucosamine 6-phosphate isomerase from rat kidney.", "content": "1. Glucosamine 6-phosphate (GlcN-6-P) isomerase of rat kidney was resistant to heating at 50--55 degrees in crude extract but not after several purification steps. GlcN-6-P and N-acetylglucosamine 6-phosphate were found to stabilize the isomerase under these conditions. They also protected the enzyme from tryptic digestion, but only GlcN-6-P was effective against inactivation by p-chloromercuribenzoate. 2. When GlcN-6P isomerase was purified from fresh kidney and kidney stored at -20 degrees, separately and under GlcN-6-P, the two preparations were different in elution profile from a hydroxyapatite column. It was subsequently found that storage of crude extract at -20 degrees resulted in molecular alterations of the enzyme. Prolonged purification appeared to affect the enzyme similarly. The molecular alterations, however, were suppressed if the extract was stored at -70 degrees. 3. These findings have been utilized to develop a procedure, which enables us to purify rat kidney GlcN-6-P isomerase without any molecular alteration and in good yield.", "contents": "Stabilization and purification of glucosamine 6-phosphate isomerase from rat kidney. 1. Glucosamine 6-phosphate (GlcN-6-P) isomerase of rat kidney was resistant to heating at 50--55 degrees in crude extract but not after several purification steps. GlcN-6-P and N-acetylglucosamine 6-phosphate were found to stabilize the isomerase under these conditions. They also protected the enzyme from tryptic digestion, but only GlcN-6-P was effective against inactivation by p-chloromercuribenzoate. 2. When GlcN-6P isomerase was purified from fresh kidney and kidney stored at -20 degrees, separately and under GlcN-6-P, the two preparations were different in elution profile from a hydroxyapatite column. It was subsequently found that storage of crude extract at -20 degrees resulted in molecular alterations of the enzyme. Prolonged purification appeared to affect the enzyme similarly. The molecular alterations, however, were suppressed if the extract was stored at -70 degrees. 3. These findings have been utilized to develop a procedure, which enables us to purify rat kidney GlcN-6-P isomerase without any molecular alteration and in good yield."}
{"id": "PMID:233944", "title": "Protein metabolism in uraemia.", "content": "Protein metabolism in uraemia is reviewed. Very few, if any, disorders of amino acid metabolism can at present confidently be attributed to uraemia per se rather than to protein/energy deprivation. Retained urea nitrogen is recycled to the liver as ammonia; a proportion is reutilized for synthesis of non-essential amino acids and, if their carbon skeletons are supplied, for synthesis of essential amino acids. Practical applications of the reutilization of non-amino nitrogen in advanced chronic renal failure are being explored. Nevertheless, uraemic individuals readily become undernourished, and they should receive as much protein as their symptoms will permit.", "contents": "Protein metabolism in uraemia. Protein metabolism in uraemia is reviewed. Very few, if any, disorders of amino acid metabolism can at present confidently be attributed to uraemia per se rather than to protein/energy deprivation. Retained urea nitrogen is recycled to the liver as ammonia; a proportion is reutilized for synthesis of non-essential amino acids and, if their carbon skeletons are supplied, for synthesis of essential amino acids. Practical applications of the reutilization of non-amino nitrogen in advanced chronic renal failure are being explored. Nevertheless, uraemic individuals readily become undernourished, and they should receive as much protein as their symptoms will permit."}
{"id": "PMID:233943", "title": "Effects of polyunsaturated fats on lipid metabolism in patients with hypertriglyceridemia.", "content": "Studies were carried out on the effects of polyunsaturated fats on lipid metabolism in 11 patients with hypertriglyceridemia. During cholesterol balance  studies performed in eight patients, the feeding of polyunsaturated fats, as compared with saturated fats, caused an increased excretion of endogenous neutral steroids, acidic steroids, or both in most patients. Increases in steroid excretions were marked in some patients and generally exceeded the decrement of cholesterol in the plasma compartment. The finding of a greater excretion of fecal steroids on polyunsaturated fats in hypertriglyceridemic patients contrasts to the lack of change in sterol balance previously reported for patients with familial hypercholesterolemia; however, other workers have found that polyunsaturated fats also enhance steroid excretion in normal subjects. In most of the patients, simultaneous studies were carried out on biliary lipid composition, hourly outputs of biliary lipids, and pool sizes of bile acids. In several but not all patients, fasting gallbladder bile became more lithogenic after institution of polyunsaturated fats. This increased lithogenicity was not due to a decrease in bile acid pools; in no case was the pool decreased by polyunsaturated fats. On the other hand, two patients showed an increased output of biliary cholesterol, and frequently there was an increase in fecal neutral steroids that were derived from cholesterol; thus, polyunsaturated fats may increase bile lithogenicity in some patients through mobilization of cholesterol into bile. Reductions in plasma cholesterol during the feeding of polyunsaturated fats was seen in most patients, and these changes were usually associated with a decrease in concentration of plasma triglycerides. In fact, the degree of cholesterol lowering was closely correlated with the extent of triglyceride reduction. Therefore, in hypertriglyceridimec patients polyunsaturated fats may contribute to cholesterol reduction by changing the metabolism of triglycerides or very low density lipoproteins. The findings of changes in the metabolism of cholesterol, bile acids, and triglycerides in the patients of this study suggests that polyunsaturated fats may cause a lowering of cholesterol through multiple mechanisms, and it seems unlikely that a single action can explain all the effects of these fats on the plasma lipids.", "contents": "Effects of polyunsaturated fats on lipid metabolism in patients with hypertriglyceridemia. Studies were carried out on the effects of polyunsaturated fats on lipid metabolism in 11 patients with hypertriglyceridemia. During cholesterol balance  studies performed in eight patients, the feeding of polyunsaturated fats, as compared with saturated fats, caused an increased excretion of endogenous neutral steroids, acidic steroids, or both in most patients. Increases in steroid excretions were marked in some patients and generally exceeded the decrement of cholesterol in the plasma compartment. The finding of a greater excretion of fecal steroids on polyunsaturated fats in hypertriglyceridemic patients contrasts to the lack of change in sterol balance previously reported for patients with familial hypercholesterolemia; however, other workers have found that polyunsaturated fats also enhance steroid excretion in normal subjects. In most of the patients, simultaneous studies were carried out on biliary lipid composition, hourly outputs of biliary lipids, and pool sizes of bile acids. In several but not all patients, fasting gallbladder bile became more lithogenic after institution of polyunsaturated fats. This increased lithogenicity was not due to a decrease in bile acid pools; in no case was the pool decreased by polyunsaturated fats. On the other hand, two patients showed an increased output of biliary cholesterol, and frequently there was an increase in fecal neutral steroids that were derived from cholesterol; thus, polyunsaturated fats may increase bile lithogenicity in some patients through mobilization of cholesterol into bile. Reductions in plasma cholesterol during the feeding of polyunsaturated fats was seen in most patients, and these changes were usually associated with a decrease in concentration of plasma triglycerides. In fact, the degree of cholesterol lowering was closely correlated with the extent of triglyceride reduction. Therefore, in hypertriglyceridimec patients polyunsaturated fats may contribute to cholesterol reduction by changing the metabolism of triglycerides or very low density lipoproteins. The findings of changes in the metabolism of cholesterol, bile acids, and triglycerides in the patients of this study suggests that polyunsaturated fats may cause a lowering of cholesterol through multiple mechanisms, and it seems unlikely that a single action can explain all the effects of these fats on the plasma lipids."}
{"id": "PMID:233946", "title": "Cation flux in the ehrlich ascites tumor cell. Evidence for Na+-for-Na+ and K+-for-K+ exchange diffusion.", "content": "In a previous study, evidence was presented for an external Na+-dependent, ouabain-insensitive component of Na+ efflux and an external K+-dependent component of K+ efflux in the Ehrlich ascites tumor cell. Evidence is now presented that these components are inhibited by the diuretic furosemide and that under conditions of normal extracellular Na+ and K+ they represent Na+-for-Na+ and K-+for-K+ exchange mechanisms. Using 86Rb to monitor K+ movements, furosemide is shown to inhibit an ouabain-insensitive component of Rb+ influx and a component of Rb+ efflux, both representing approx. 30 percent of the total flux. Inhibition of Rb+ efflux is greatly reduced by removal of extracellular K+. Furosemide does not alter steady-state levels of intracellular K+ and it does not prevent cells depleted of K+ by incubation in the cold from regaining K+ upon warming. Using 22Na to monitor Na+ movements, furosemide is shown to inhibit an ouabain-insensitive component of unidirectional Na+ efflux which represents approx. 22 percent of total Na+ efflux. Furosemide does not alter steady-state levels of intracellular Na+ and does not prevent removal of intracellular Na+ upon warming from cells loaded with Na+ by preincubation in the cold. The ability of furosemide to affect unidirectional Na+ and K+ fluxes but not net fluxes is consistent with the conclusion that these components of cation movement across the cell membrane represent one-for-one exchange mechanisms. Data are also presented which demonstrate that the uptake of alpha-aminoisobutyrate is not affected by furosemide. This indicates that these components of cation flux are not directly involved in the Na+-dependent amino acid transport system A.", "contents": "Cation flux in the ehrlich ascites tumor cell. Evidence for Na+-for-Na+ and K+-for-K+ exchange diffusion. In a previous study, evidence was presented for an external Na+-dependent, ouabain-insensitive component of Na+ efflux and an external K+-dependent component of K+ efflux in the Ehrlich ascites tumor cell. Evidence is now presented that these components are inhibited by the diuretic furosemide and that under conditions of normal extracellular Na+ and K+ they represent Na+-for-Na+ and K-+for-K+ exchange mechanisms. Using 86Rb to monitor K+ movements, furosemide is shown to inhibit an ouabain-insensitive component of Rb+ influx and a component of Rb+ efflux, both representing approx. 30 percent of the total flux. Inhibition of Rb+ efflux is greatly reduced by removal of extracellular K+. Furosemide does not alter steady-state levels of intracellular K+ and it does not prevent cells depleted of K+ by incubation in the cold from regaining K+ upon warming. Using 22Na to monitor Na+ movements, furosemide is shown to inhibit an ouabain-insensitive component of unidirectional Na+ efflux which represents approx. 22 percent of total Na+ efflux. Furosemide does not alter steady-state levels of intracellular Na+ and does not prevent removal of intracellular Na+ upon warming from cells loaded with Na+ by preincubation in the cold. The ability of furosemide to affect unidirectional Na+ and K+ fluxes but not net fluxes is consistent with the conclusion that these components of cation movement across the cell membrane represent one-for-one exchange mechanisms. Data are also presented which demonstrate that the uptake of alpha-aminoisobutyrate is not affected by furosemide. This indicates that these components of cation flux are not directly involved in the Na+-dependent amino acid transport system A."}
{"id": "PMID:233950", "title": "Bathtub refinisher's lung: an unusual response to toluene diisocyanate.", "content": "Immunologic and inhalation challenge studies were performed on a patient engaged in bathtub refinishing who developed systemic and respiratory symptoms suggestive of hypersensitivity pneumonitis temporally related to his occupation. The refinishing process used a catalyst containing toluene diisocyanate, and all clinical features of the disorder were reproduced by challenge. No immunologic mechanism could be identified. A change of occupation resulted in complete relief of symptoms.", "contents": "Bathtub refinisher's lung: an unusual response to toluene diisocyanate. Immunologic and inhalation challenge studies were performed on a patient engaged in bathtub refinishing who developed systemic and respiratory symptoms suggestive of hypersensitivity pneumonitis temporally related to his occupation. The refinishing process used a catalyst containing toluene diisocyanate, and all clinical features of the disorder were reproduced by challenge. No immunologic mechanism could be identified. A change of occupation resulted in complete relief of symptoms."}
{"id": "PMID:233954", "title": "Sex differences in the intramuscular absorption and bioavailability of cephradine.", "content": "Six male and six female volunteers each received a single intramuscular injection of cephradine, a new cephalosporin antibiotic, once weekly for 3 consecutive weeks. The drug was injected into the gluteus maximus, vastus lateralis, or deltoid muscle groups. Injection sites were rotated each week so that each subject received an injection into each muscle. Pharmacokinetic evaluation of serum concentrations and urinary excretion data indicated a sex difference with respect to the rate and extent of cephradine absorption from the three injection sites. Smaller areas under the curve and absorption rate constants were observed for females after injection into each muscle group. The most striking difference was observed when cephradine was injected into the gluteus maximus muscle, where the exponential function describing the alpha phase was observed to be 1.16 +/- 0.17 hr(-1) for females and 2.70 +/- 0.34 hr(-1) for males. Total area under the mean serum concentration-time curves, mean time to peak, and peak height parameters consistent with the slower rate of absorption and lesser bioavailability in females were observed. These results show that the vastus lateralis or deltoid muscle groups are preferable to the gluteus maximus as injection sites because of the more rapid rates of drug absorption from those muscles.", "contents": "Sex differences in the intramuscular absorption and bioavailability of cephradine. Six male and six female volunteers each received a single intramuscular injection of cephradine, a new cephalosporin antibiotic, once weekly for 3 consecutive weeks. The drug was injected into the gluteus maximus, vastus lateralis, or deltoid muscle groups. Injection sites were rotated each week so that each subject received an injection into each muscle. Pharmacokinetic evaluation of serum concentrations and urinary excretion data indicated a sex difference with respect to the rate and extent of cephradine absorption from the three injection sites. Smaller areas under the curve and absorption rate constants were observed for females after injection into each muscle group. The most striking difference was observed when cephradine was injected into the gluteus maximus muscle, where the exponential function describing the alpha phase was observed to be 1.16 +/- 0.17 hr(-1) for females and 2.70 +/- 0.34 hr(-1) for males. Total area under the mean serum concentration-time curves, mean time to peak, and peak height parameters consistent with the slower rate of absorption and lesser bioavailability in females were observed. These results show that the vastus lateralis or deltoid muscle groups are preferable to the gluteus maximus as injection sites because of the more rapid rates of drug absorption from those muscles."}
{"id": "PMID:233958", "title": "Antibodies to Epstein-Barr viral capsid and early antigens associated with Burkitt's lymphoma and lymphoblastic lymphosarcoma in Israel.", "content": "Before and/or after chemotherapy was administered to patients with Burkitt's lymphoma (BL) or lymphoblastic lymphosarcoma (LLS), their sera and those of matched controls were tested for antibodies to Epstein-Barr virus (EBV) capsid antigen (VCA) and early antigen by the indirect immunofluorescence method. Ten of the 16 BL patients were Arab children and 8 of the 11 LLS patients were Jews of Asian-African origin. Although half the BL patients did not have elevated antibody titers when their disease was diagnosed, significantly higher ones were detected in the BL group as compared with the LLS patients and their matched controls; Arab patients had the highest titers. IgM antibodies specific for VCA were found in 2 patients concurrently with elevated titers. We found no correlation between the clinical course of BL and the patients' antibody titers to EBV.", "contents": "Antibodies to Epstein-Barr viral capsid and early antigens associated with Burkitt's lymphoma and lymphoblastic lymphosarcoma in Israel. Before and/or after chemotherapy was administered to patients with Burkitt's lymphoma (BL) or lymphoblastic lymphosarcoma (LLS), their sera and those of matched controls were tested for antibodies to Epstein-Barr virus (EBV) capsid antigen (VCA) and early antigen by the indirect immunofluorescence method. Ten of the 16 BL patients were Arab children and 8 of the 11 LLS patients were Jews of Asian-African origin. Although half the BL patients did not have elevated antibody titers when their disease was diagnosed, significantly higher ones were detected in the BL group as compared with the LLS patients and their matched controls; Arab patients had the highest titers. IgM antibodies specific for VCA were found in 2 patients concurrently with elevated titers. We found no correlation between the clinical course of BL and the patients' antibody titers to EBV."}
{"id": "PMID:233959", "title": "Inversion homozygosity of chromosome no. 9 in a higly inbred kindred.", "content": "A pericentric inversion of chromosome no. 9 was present in seven of 10 members of a highly inbred kindred investigated; two were inversion homozygotes and five were heterozygotes. Inversion homozygosity was observed in both the propositus, ascertained because of ambiguous genitalia, and his phenotypically normal father. A phenotypically normal sister and brother with similar clinical findings proved to be inversion heterozygotes. These findings conclude that no causal relationship exists between the inversion and the abnormal phenotype.", "contents": "Inversion homozygosity of chromosome no. 9 in a higly inbred kindred. A pericentric inversion of chromosome no. 9 was present in seven of 10 members of a highly inbred kindred investigated; two were inversion homozygotes and five were heterozygotes. Inversion homozygosity was observed in both the propositus, ascertained because of ambiguous genitalia, and his phenotypically normal father. A phenotypically normal sister and brother with similar clinical findings proved to be inversion heterozygotes. These findings conclude that no causal relationship exists between the inversion and the abnormal phenotype."}
{"id": "PMID:233968", "title": "Inhibition of carbonic anhydrase by parathyroid hormone and cyclic AMP in rat renal cortex in vitro.", "content": "It has been demonstrated that parathyroid hormone (PTH) inhibits the proximal tubular reabsorption of bicarbonate, and increases the urinary excretion of that ion. There is also a qualitative similarity between the alterations of the proximal tubular reabsorption of phosphate, sodium, and water after PTH administration and after acetazolamide administration. These findings suggest that the renal effect of PTH is possibly mediated through the inhibition of carbonic anhydrase in proximal tubules. Therefore, a possible inhibitory effect of PTH on carbonic anhydrase was evaluated in the homogenate of rat renal cortex by an indicator titration method. Incubation of cortical homogenates with PTH for 10 min at 37degreesC inhibited carbonic anhydrase activity. The inhibitory effect of PTH was ATP-, Mg++-, and K+-dependent and temperature-dependent; inactivation of PTH by heating at 100degreesC abolished the effect of PTH both to activate adenylate cyclase and to inhibit carbonic anhydrase. Calcium 5 mM also partially abolished effects of PTH to activate adenylate cyclase and to inhibit carbonic anhydrase. The inhibitory effect of PTH on carbonic anhydrase was specific to renal cortex. Cyclic AMP, the intracellular messenger substance for PTH, also inhibited carbonic anhydrase in renal cortex. The cyclic AMP-induced inhibition was also Mg++ dependent and temperature dependent, and required preincubation at 37degreesC. But 5'-AMP, a metabolic derivative of cyclic AMP without its biological effect, had no inhibitory effect on carbonic anhydrase. All the above results are consistent with the hypothesis that PTH inhibits proximal tubular reabsorption of bicarbonate and phosphate through the inhibition of carbonic anhydrase, and that inhibitory effect is mediated through the cyclic AMP system.", "contents": "Inhibition of carbonic anhydrase by parathyroid hormone and cyclic AMP in rat renal cortex in vitro. It has been demonstrated that parathyroid hormone (PTH) inhibits the proximal tubular reabsorption of bicarbonate, and increases the urinary excretion of that ion. There is also a qualitative similarity between the alterations of the proximal tubular reabsorption of phosphate, sodium, and water after PTH administration and after acetazolamide administration. These findings suggest that the renal effect of PTH is possibly mediated through the inhibition of carbonic anhydrase in proximal tubules. Therefore, a possible inhibitory effect of PTH on carbonic anhydrase was evaluated in the homogenate of rat renal cortex by an indicator titration method. Incubation of cortical homogenates with PTH for 10 min at 37degreesC inhibited carbonic anhydrase activity. The inhibitory effect of PTH was ATP-, Mg++-, and K+-dependent and temperature-dependent; inactivation of PTH by heating at 100degreesC abolished the effect of PTH both to activate adenylate cyclase and to inhibit carbonic anhydrase. Calcium 5 mM also partially abolished effects of PTH to activate adenylate cyclase and to inhibit carbonic anhydrase. The inhibitory effect of PTH on carbonic anhydrase was specific to renal cortex. Cyclic AMP, the intracellular messenger substance for PTH, also inhibited carbonic anhydrase in renal cortex. The cyclic AMP-induced inhibition was also Mg++ dependent and temperature dependent, and required preincubation at 37degreesC. But 5'-AMP, a metabolic derivative of cyclic AMP without its biological effect, had no inhibitory effect on carbonic anhydrase. All the above results are consistent with the hypothesis that PTH inhibits proximal tubular reabsorption of bicarbonate and phosphate through the inhibition of carbonic anhydrase, and that inhibitory effect is mediated through the cyclic AMP system."}
{"id": "PMID:233969", "title": "Concanavalin A inhibits tissue factor coagulant activity.", "content": "Concanavalin A (con A) is a potent inhibitor of coagulant activity of native tissue factor. Coagulant activity is recovered by addition of alpha-methyl-D-glucoside to inhibited tissue factor. Inclusion of alpha-methyl-D-glucose during incubation of con A with tissue factor preserves coagulant activity. These data suggest that con A interacts reversibly with a carbohydrate residue in such a way as to inhibit coagulant activity of the molecule. Purified tissue factor apoprotein has been recombined with mixed brain phospholipids or purified phospholipids (phosphatidyl ethanolamine or a mixture of phosphatidyl choline with phosphatidyl serine). These preparations were also completely but reversibly inhibited by con A. Thus, purified tissue factor apoprotein appears to donate the affected carbohydrate residue.", "contents": "Concanavalin A inhibits tissue factor coagulant activity. Concanavalin A (con A) is a potent inhibitor of coagulant activity of native tissue factor. Coagulant activity is recovered by addition of alpha-methyl-D-glucoside to inhibited tissue factor. Inclusion of alpha-methyl-D-glucose during incubation of con A with tissue factor preserves coagulant activity. These data suggest that con A interacts reversibly with a carbohydrate residue in such a way as to inhibit coagulant activity of the molecule. Purified tissue factor apoprotein has been recombined with mixed brain phospholipids or purified phospholipids (phosphatidyl ethanolamine or a mixture of phosphatidyl choline with phosphatidyl serine). These preparations were also completely but reversibly inhibited by con A. Thus, purified tissue factor apoprotein appears to donate the affected carbohydrate residue."}
{"id": "PMID:233970", "title": "The cariogenicity of snack foods and confections.", "content": "A survey of the relationship between caries prevalence and the consumption of sugar and other foods by man has been interpreted to show that snack foods share importance with sucrose in caries causation. Support for this conclusion is found in animal experiments and some in vitro and in vivo tests.", "contents": "The cariogenicity of snack foods and confections. A survey of the relationship between caries prevalence and the consumption of sugar and other foods by man has been interpreted to show that snack foods share importance with sucrose in caries causation. Support for this conclusion is found in animal experiments and some in vitro and in vivo tests."}
{"id": "PMID:233974", "title": "Quantitative studies of pinocytosis. II. Kinetics of protein uptake and digestion by rat yolk sac cultured in vitro.", "content": "Pinocytic uptake of 125I-labeled bovine serum albumin by 17.5-day rat visceral yolk sac cultured in vitro has been examined. Uptake was followed by intracellular digestion and, after an initial period, the content of radioactivity in the tissue itself remained constant during the incubation. Radiolabel was returned to the culture medium predominantly as (125I)iodotyrosine; exocytosis of undigested protein did not occur. The rate of uptake of labeled protein, which was constant within an experiment and reproducible between experiments, was much higher than that of a nondigestible macromolecule, 125I-labeled polyvinylpyrrolidone. The higher rate of uptake was a consequence of the protein entering the cells chiefly by adsorption to the plasma membrane being internalized; 125I-labeled albumin did not stimualte, nor did 125I-labeled polyvinylpyrrolidone inhibit pinocytosis. Different preparations of 125I-labeled albumin had characteristically different rates of uptake, probably reflecting differences in affinity for plasma membrane receptors. The physiological significance of the findings is discussed.", "contents": "Quantitative studies of pinocytosis. II. Kinetics of protein uptake and digestion by rat yolk sac cultured in vitro. Pinocytic uptake of 125I-labeled bovine serum albumin by 17.5-day rat visceral yolk sac cultured in vitro has been examined. Uptake was followed by intracellular digestion and, after an initial period, the content of radioactivity in the tissue itself remained constant during the incubation. Radiolabel was returned to the culture medium predominantly as (125I)iodotyrosine; exocytosis of undigested protein did not occur. The rate of uptake of labeled protein, which was constant within an experiment and reproducible between experiments, was much higher than that of a nondigestible macromolecule, 125I-labeled polyvinylpyrrolidone. The higher rate of uptake was a consequence of the protein entering the cells chiefly by adsorption to the plasma membrane being internalized; 125I-labeled albumin did not stimualte, nor did 125I-labeled polyvinylpyrrolidone inhibit pinocytosis. Different preparations of 125I-labeled albumin had characteristically different rates of uptake, probably reflecting differences in affinity for plasma membrane receptors. The physiological significance of the findings is discussed."}
{"id": "PMID:233975", "title": "A fine structure study of the anthocodium in Renilla m\u00fclleri. Evidence for the existence of a bioluminescent organelle, the luminelle.", "content": "A fine structure study of the anthocodium of the sea pansy, Renilla m\u00fclleri, was undertaken. The anthocodium, a known site of bioluminescence, was selected in order to determine whether a structural entity could be found which would satisfy the biochemical and physiological features associated with the known sites of bioluminescence in this animal. These sites, termed lumisomes, have previously been shown to be small (0.1-0.2 mum), membrane-enclosed vesicles which contain all the proteins necessary for bioluminescence and its immediate control. One of the lumisomal proteins is an intensely green fluorescent protein and has been used as a probe for the detection of the cellular sites of bioluminescence. This green fluorescence was associated only with gastrodermal cells. We report the identification of a unique morphological entity, restricted to the cells of the gastrodermis, which satisfies the biochemical and physiological requirements for bioluminescence in Renilla. It is a large (4-6 mum), membrane-bounded subcellular organelle comparable in size to a subcellular structure whose green fluorescence is typically associated with the in vivo bioluminescence. Furthermore, it is filled with smaller membrane-bounded vesicles which have the same size and shape as the lumisomes. We suggest that the organelle identified in this study be termed a luminelle.", "contents": "A fine structure study of the anthocodium in Renilla m\u00fclleri. Evidence for the existence of a bioluminescent organelle, the luminelle. A fine structure study of the anthocodium of the sea pansy, Renilla m\u00fclleri, was undertaken. The anthocodium, a known site of bioluminescence, was selected in order to determine whether a structural entity could be found which would satisfy the biochemical and physiological features associated with the known sites of bioluminescence in this animal. These sites, termed lumisomes, have previously been shown to be small (0.1-0.2 mum), membrane-enclosed vesicles which contain all the proteins necessary for bioluminescence and its immediate control. One of the lumisomal proteins is an intensely green fluorescent protein and has been used as a probe for the detection of the cellular sites of bioluminescence. This green fluorescence was associated only with gastrodermal cells. We report the identification of a unique morphological entity, restricted to the cells of the gastrodermis, which satisfies the biochemical and physiological requirements for bioluminescence in Renilla. It is a large (4-6 mum), membrane-bounded subcellular organelle comparable in size to a subcellular structure whose green fluorescence is typically associated with the in vivo bioluminescence. Furthermore, it is filled with smaller membrane-bounded vesicles which have the same size and shape as the lumisomes. We suggest that the organelle identified in this study be termed a luminelle."}
{"id": "PMID:234005", "title": "Beta-adrenergic blockade in diuretic-treated patients with essential hypertension.", "content": "The influence of beta-adrenergic blockade (160 mg per day of propranolol for four weeks) on plasma renin activity, plasma volume, and arterial pressure was explored in 20 patients with essential hypertension with hyper-reninemia from long-term diuretic therapy. In 15 of these patients renin activity remained elevated (range, 3.1 to 23.0 ng per milliliter). Plasma volume was unchanged in eight, increased in 11 and reduced in one. In 17 subjects mean arterial pressure decreased by more than 10 mm Hg, but these impressive reductions could not be explained by quantitative changes in either renin activity (r equals 0.1) or plasma volume (r equals 0.1). These data suggest that suppression of plasma renin activity by beta-adrenergic blockade is not attainable during diuretic therapy and is not the major factor responsible for the antihypertensive action of propranolol.", "contents": "Beta-adrenergic blockade in diuretic-treated patients with essential hypertension. The influence of beta-adrenergic blockade (160 mg per day of propranolol for four weeks) on plasma renin activity, plasma volume, and arterial pressure was explored in 20 patients with essential hypertension with hyper-reninemia from long-term diuretic therapy. In 15 of these patients renin activity remained elevated (range, 3.1 to 23.0 ng per milliliter). Plasma volume was unchanged in eight, increased in 11 and reduced in one. In 17 subjects mean arterial pressure decreased by more than 10 mm Hg, but these impressive reductions could not be explained by quantitative changes in either renin activity (r equals 0.1) or plasma volume (r equals 0.1). These data suggest that suppression of plasma renin activity by beta-adrenergic blockade is not attainable during diuretic therapy and is not the major factor responsible for the antihypertensive action of propranolol."}
{"id": "PMID:234007", "title": "Some unusual cases of apexification subsequent to trauma.", "content": "Three cases are reported in which apexification occurred without the benefit of endodontic treatment. These reports illustrate that immature teeth which are avulsed and replanted, dislocated and repositioned, or traumatized with pulp necrosis supervening, may progress to form complete apices without intracanal therapy. The value of using calcium hydroxide is not in question, but may not be as essential an aid to apical closure as was previously thought. In one case, the appearance of isolated apixes forming, deep in the bone after loss of very immature lateral incisors poses the question of whether this event does not occur more frequently after extraction of newly erupted or young impacted teeth.", "contents": "Some unusual cases of apexification subsequent to trauma. Three cases are reported in which apexification occurred without the benefit of endodontic treatment. These reports illustrate that immature teeth which are avulsed and replanted, dislocated and repositioned, or traumatized with pulp necrosis supervening, may progress to form complete apices without intracanal therapy. The value of using calcium hydroxide is not in question, but may not be as essential an aid to apical closure as was previously thought. In one case, the appearance of isolated apixes forming, deep in the bone after loss of very immature lateral incisors poses the question of whether this event does not occur more frequently after extraction of newly erupted or young impacted teeth."}
{"id": "PMID:234008", "title": "The protean manifestations of Crohn's disease.", "content": "Crohn's disease is a perplexing disease with a high rate of morbidity and complications. The incidence appears to be increasing. The cause is unknown, and response to medical therapy has been disappointing. Diagnosis may be very difficult and often is delayed. A high proportion of patients eventually require surgery, and an appreciable percentage will have recurrence of disease afterward. The prognosis in terms of responsiveness to medical therapy is believed to be poorer than the prognosis of ulcerative colitis. A national cooperative study to assess drug therapy prospectively is under way.", "contents": "The protean manifestations of Crohn's disease. Crohn's disease is a perplexing disease with a high rate of morbidity and complications. The incidence appears to be increasing. The cause is unknown, and response to medical therapy has been disappointing. Diagnosis may be very difficult and often is delayed. A high proportion of patients eventually require surgery, and an appreciable percentage will have recurrence of disease afterward. The prognosis in terms of responsiveness to medical therapy is believed to be poorer than the prognosis of ulcerative colitis. A national cooperative study to assess drug therapy prospectively is under way."}
{"id": "PMID:234009", "title": "Simple chronic constipation: pathophysiology and management.", "content": "Chronic constipation is not a simple problem. It is often related to fundamental beliefs and habits. Once it has been established that the cause is not an organic disorder, the physician must take pains to explore with the patient other possible causes. Simple, inorganic constipation can usually be traced to poor diet or poor habits. The physician should provide simple explanations of the mechanisms involved in the act of elimination and detailed instructions on appropriate food and water intake and the development of regular habits. Laxatives should be prescribed only if absolutely necessary and if the patient taking them can be carefully observed.", "contents": "Simple chronic constipation: pathophysiology and management. Chronic constipation is not a simple problem. It is often related to fundamental beliefs and habits. Once it has been established that the cause is not an organic disorder, the physician must take pains to explore with the patient other possible causes. Simple, inorganic constipation can usually be traced to poor diet or poor habits. The physician should provide simple explanations of the mechanisms involved in the act of elimination and detailed instructions on appropriate food and water intake and the development of regular habits. Laxatives should be prescribed only if absolutely necessary and if the patient taking them can be carefully observed."}
{"id": "PMID:234010", "title": "Successful orthotopic allotransplantation of hearts from dogs in irreversible shock.", "content": "The viability of the heart from irreversibly shocked dogs was evaluated. Thirty-one mongrel dogs were used to develop a uniformly lethal hemorrhagic shock model. The final model utilized a 30 mm. Hg mean arterial pressure with a 40 percent decompensation (uptake of reservoir blood). All control dogs subjected to this procedure died within 24 hours. Eleven hearts were transplanted following the shock procedure. Blood samples were drawn at intervals and analyzed for Po2, pH, glucose, oxygen content, and hematocrit. Cardiac outputs and ECG's were taken before and after transplant. All parameters measured returned to control levels following the transplants. Of the dogs receiving heart transplants, 10 survived more than 24 hours and eight survived more than 7 days. Compared with the survival of the shock model experiments, the survival of the transplant recipients was significant at the p less than 0.01 level. These results suggest that deterioration of the heart is not the factor which prevents recovery from irreversible hemorrhagic shock.", "contents": "Successful orthotopic allotransplantation of hearts from dogs in irreversible shock. The viability of the heart from irreversibly shocked dogs was evaluated. Thirty-one mongrel dogs were used to develop a uniformly lethal hemorrhagic shock model. The final model utilized a 30 mm. Hg mean arterial pressure with a 40 percent decompensation (uptake of reservoir blood). All control dogs subjected to this procedure died within 24 hours. Eleven hearts were transplanted following the shock procedure. Blood samples were drawn at intervals and analyzed for Po2, pH, glucose, oxygen content, and hematocrit. Cardiac outputs and ECG's were taken before and after transplant. All parameters measured returned to control levels following the transplants. Of the dogs receiving heart transplants, 10 survived more than 24 hours and eight survived more than 7 days. Compared with the survival of the shock model experiments, the survival of the transplant recipients was significant at the p less than 0.01 level. These results suggest that deterioration of the heart is not the factor which prevents recovery from irreversible hemorrhagic shock."}
{"id": "PMID:234011", "title": "Assistants to primary physicians in California.", "content": "The mid-level practitioner movement is no longer experimental; nurse practitioners and physician's assistants in California have proved to fill a necessary and viable professional role in the delivery of primary health care. The physician's assistant law (AB2109) and the Experimental Manpower Act (AB1503) have facilitated the training and functioning of these new health care professionals; more comprehensive laws are still needed to permit optimal utilization. National agencies for approval of teaching programs and testing of individual graduates will play an increasing role in the accreditation and certification procedures. Professional role difficulties, issues of sex and questions of delegation of responsibility are being resolved and it is hoped that a more equitable and patient-oriented system is evolving.", "contents": "Assistants to primary physicians in California. The mid-level practitioner movement is no longer experimental; nurse practitioners and physician's assistants in California have proved to fill a necessary and viable professional role in the delivery of primary health care. The physician's assistant law (AB2109) and the Experimental Manpower Act (AB1503) have facilitated the training and functioning of these new health care professionals; more comprehensive laws are still needed to permit optimal utilization. National agencies for approval of teaching programs and testing of individual graduates will play an increasing role in the accreditation and certification procedures. Professional role difficulties, issues of sex and questions of delegation of responsibility are being resolved and it is hoped that a more equitable and patient-oriented system is evolving."}
{"id": "PMID:234013", "title": "Aromatic amino acid hydroxylase inhibitors. 4. 3-Substituted alpha-methyltyrosines.", "content": "In the present study a series of 3-alkenyl-alpha-methyltyrosines and their corresponding 3-alkyl-and dihydrobenzofuran analogs was synthesized for potential tyrosine hydroxylase (TH) inhibitory activity. The appropriately substituted hydantoins IIIa and IIIb, which were prepared from the corresponding allyloxybenzylhydantoins IIa and IIb through Claisen rearrangement, served as intermediates for the synthesis of these amino acids. TH inhibition was reduced upon either saturation of the double bond in the side chain or cyclization to form the dihydrobenzofuran analogs. Formation of the epoxide had a similar effect. The inhibitory activity of these compounds against aromatic amino acid decarboxylase (AADC) and dopamine beta-hydroxylase (DBH) was also investigated. Unsaturation, in both cases, decreases the inhibitory activity; however, the presence of a free phenolic group appears to be essential for AACD inhibitory activity.", "contents": "Aromatic amino acid hydroxylase inhibitors. 4. 3-Substituted alpha-methyltyrosines. In the present study a series of 3-alkenyl-alpha-methyltyrosines and their corresponding 3-alkyl-and dihydrobenzofuran analogs was synthesized for potential tyrosine hydroxylase (TH) inhibitory activity. The appropriately substituted hydantoins IIIa and IIIb, which were prepared from the corresponding allyloxybenzylhydantoins IIa and IIb through Claisen rearrangement, served as intermediates for the synthesis of these amino acids. TH inhibition was reduced upon either saturation of the double bond in the side chain or cyclization to form the dihydrobenzofuran analogs. Formation of the epoxide had a similar effect. The inhibitory activity of these compounds against aromatic amino acid decarboxylase (AADC) and dopamine beta-hydroxylase (DBH) was also investigated. Unsaturation, in both cases, decreases the inhibitory activity; however, the presence of a free phenolic group appears to be essential for AACD inhibitory activity."}
{"id": "PMID:234014", "title": "Amidines and related compounds. 6. Studies on structure-activity relationships of antihypertensive and antisecretory agents related to clonidine.", "content": "Correlations of antihypertensive and antisecretory activities with various structural modifications of the antihypertensive agent clonidine (2-(2,6-dichlorophenylimino)imidazolidine) are described. Eleven chemical classes of compounds containing an \"amidine\" moiety were prepared in this study. The antihypertensive activity of these compounds was evaluated in metacorticoid hypertensive rats and unanesthetized neurogenic hypertensive dogs following oral administration. Antisecretory activity was evaluated in fistula rats by measuring pH and volume of gastric secretion. Two compounds, 2-(2,6-dimethylphenylimino)imidazolidine and 2-(2,6-dichlorophenylimino)pyrrolidine, are particularly effective antisecretory agents with minimal antihypertensive activity.", "contents": "Amidines and related compounds. 6. Studies on structure-activity relationships of antihypertensive and antisecretory agents related to clonidine. Correlations of antihypertensive and antisecretory activities with various structural modifications of the antihypertensive agent clonidine (2-(2,6-dichlorophenylimino)imidazolidine) are described. Eleven chemical classes of compounds containing an \"amidine\" moiety were prepared in this study. The antihypertensive activity of these compounds was evaluated in metacorticoid hypertensive rats and unanesthetized neurogenic hypertensive dogs following oral administration. Antisecretory activity was evaluated in fistula rats by measuring pH and volume of gastric secretion. Two compounds, 2-(2,6-dimethylphenylimino)imidazolidine and 2-(2,6-dichlorophenylimino)pyrrolidine, are particularly effective antisecretory agents with minimal antihypertensive activity."}
{"id": "PMID:234015", "title": "Oxygen binding by hemocyanin from Levantina hierosolima. I. Exclusion of subunit interactions as a basis for cooperativity.", "content": "The effect of oxygen on the distribution of hemocyanin from Levantina hierosolima among the three sedimenting species 20, 60, and 100 S was determined under two sets of experimental conditions: (a) at pH 7.63 in the absence of Ca2+, where oxygen binding in noncooperative; (b) at pH 8.20 in the presence of 2 x 10-3 M Ca2+, where oxygen binding is cooperative. A comparison of the results in the two cases eliminates the possibility that equilibrium between species with different oxygen affinities is responsible for the cooperative behavior. Cooperative oxygen binding was demonstrated for the 20S subunits at pH 8.80 and 1 x 10-3 M Ca2+. Under these conditions, the concentration of calcium is sufficient to affect the oxygen affinity, but the concentration of calcium plus proton is not sufficient to bring about association. The findings exclude interactions among 20S subunits as a basis for cooperativity in hemocyanin.", "contents": "Oxygen binding by hemocyanin from Levantina hierosolima. I. Exclusion of subunit interactions as a basis for cooperativity. The effect of oxygen on the distribution of hemocyanin from Levantina hierosolima among the three sedimenting species 20, 60, and 100 S was determined under two sets of experimental conditions: (a) at pH 7.63 in the absence of Ca2+, where oxygen binding in noncooperative; (b) at pH 8.20 in the presence of 2 x 10-3 M Ca2+, where oxygen binding is cooperative. A comparison of the results in the two cases eliminates the possibility that equilibrium between species with different oxygen affinities is responsible for the cooperative behavior. Cooperative oxygen binding was demonstrated for the 20S subunits at pH 8.80 and 1 x 10-3 M Ca2+. Under these conditions, the concentration of calcium is sufficient to affect the oxygen affinity, but the concentration of calcium plus proton is not sufficient to bring about association. The findings exclude interactions among 20S subunits as a basis for cooperativity in hemocyanin."}
{"id": "PMID:234016", "title": "Oxygen binding by hemocyanin from Levantina hierosolima. II. Interpretation of cooperativity in terms of ligand-ligand linkage.", "content": "Oxygen binding by hemocyanin from Levantina hierosolima was studied at pH 7.30, in solutions containing calcium in the concentration range 0-1 M. The binding was found to be cooperative, the degree of cooperativity being calcium concentration dependent. The dependence on calcium concentration of the affinity toward oxygen for both deoxygenated and oxygenated hemocyanin was interpreted in terms of two oxygen-linked calcium ions, one promoting and the other opposing oxygen binding. The results show that cooperativity may be fully explained on the basis of a coupling of the free energy of binding between calcium and oxygen.", "contents": "Oxygen binding by hemocyanin from Levantina hierosolima. II. Interpretation of cooperativity in terms of ligand-ligand linkage. Oxygen binding by hemocyanin from Levantina hierosolima was studied at pH 7.30, in solutions containing calcium in the concentration range 0-1 M. The binding was found to be cooperative, the degree of cooperativity being calcium concentration dependent. The dependence on calcium concentration of the affinity toward oxygen for both deoxygenated and oxygenated hemocyanin was interpreted in terms of two oxygen-linked calcium ions, one promoting and the other opposing oxygen binding. The results show that cooperativity may be fully explained on the basis of a coupling of the free energy of binding between calcium and oxygen."}
{"id": "PMID:234017", "title": "Phase transitions and phase separations in phospholipid membranes induced by changes in temperature, pH, and concentration of bivalent cations.", "content": "Differential scanning calorimetry (DSC) and fluorescence polarization of embedded probe molecules were used to detect phase behavior of various phospholipids. The techniques were directly compared for detecting the transition of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidic acid (DPPA) dispersed in aqueous salt solutions. Excellent agreement occurred in the case of phosphatidylcholine; however, in the case of phosphatidic acid, at pH 6.5, transitions detected by fluorescence polarization using the disc-like perylene molecule occurred about 10 degrees lower than those detected by DSC. Discrepancy between fluorescence and DSC methods is eliminated by using a rod-like molecule, diphenylhexatriene (DPH). Both techniques show that doubly ionizing the phosphate group reduces the Tc by about 9 degrees. Direct pH titration of fluidity can be accomplished and this effect is most dramatic when membranes are in their transition temperature range (ca. 50 degrees). Phosphatidic acid transitions occur at higher temperatures, and have appreciably lower transition enthalpies and entropies than phosphatidylcholine. These effect could not be explained simply on the basis of double layer electrostatics and several other factors were discussed in an attempt to rationalize the results. Addition of monovalent cations (0.01-0.5 M) is shown to increase the Tc of dipalmitoylphosphatidylglycerol by less than 3 degrees. However, addition of (1 x 10-3 M) Ca2+ abolishes the phase transition of both phosphatidyglycerol and phosphatidylserine in the range 0-70 degrees. Preliminary X-ray evidence indicates the phosphatidylserine-Ca2+ bilayers are in a crystalline state at 24 degrees. In contrast, 5 x 10-3 M Mg2+ only broadens the transition and increases the Tc indicating a considerable difference between the effects of Ca2+ and Mg2+. Neutralization of PS increases the Tc from 6 degrees (at pH 7.4) to 20-26 degrees (at pH 2.5-3.0) but does not abolish the transition, suggesting the Ca2+ effect involves more than charge neutralization. Addition of Ca2+ to mixed phosphatidylserine-phosphatidylcholine dispersions, induces a phase separation of the dipalmitoyl- (and also distearoyl-) phosphatidylcholine as seen by the appearance of a new endothermic peak at 41 degrees (58 degrees). Similarly, in mixed (dipalmitoyl) phosphatidic acid-phosphatidylcholine (2:1) dispersions, Ca2+ again can separate the phosphatidylcholine component.", "contents": "Phase transitions and phase separations in phospholipid membranes induced by changes in temperature, pH, and concentration of bivalent cations. Differential scanning calorimetry (DSC) and fluorescence polarization of embedded probe molecules were used to detect phase behavior of various phospholipids. The techniques were directly compared for detecting the transition of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidic acid (DPPA) dispersed in aqueous salt solutions. Excellent agreement occurred in the case of phosphatidylcholine; however, in the case of phosphatidic acid, at pH 6.5, transitions detected by fluorescence polarization using the disc-like perylene molecule occurred about 10 degrees lower than those detected by DSC. Discrepancy between fluorescence and DSC methods is eliminated by using a rod-like molecule, diphenylhexatriene (DPH). Both techniques show that doubly ionizing the phosphate group reduces the Tc by about 9 degrees. Direct pH titration of fluidity can be accomplished and this effect is most dramatic when membranes are in their transition temperature range (ca. 50 degrees). Phosphatidic acid transitions occur at higher temperatures, and have appreciably lower transition enthalpies and entropies than phosphatidylcholine. These effect could not be explained simply on the basis of double layer electrostatics and several other factors were discussed in an attempt to rationalize the results. Addition of monovalent cations (0.01-0.5 M) is shown to increase the Tc of dipalmitoylphosphatidylglycerol by less than 3 degrees. However, addition of (1 x 10-3 M) Ca2+ abolishes the phase transition of both phosphatidyglycerol and phosphatidylserine in the range 0-70 degrees. Preliminary X-ray evidence indicates the phosphatidylserine-Ca2+ bilayers are in a crystalline state at 24 degrees. In contrast, 5 x 10-3 M Mg2+ only broadens the transition and increases the Tc indicating a considerable difference between the effects of Ca2+ and Mg2+. Neutralization of PS increases the Tc from 6 degrees (at pH 7.4) to 20-26 degrees (at pH 2.5-3.0) but does not abolish the transition, suggesting the Ca2+ effect involves more than charge neutralization. Addition of Ca2+ to mixed phosphatidylserine-phosphatidylcholine dispersions, induces a phase separation of the dipalmitoyl- (and also distearoyl-) phosphatidylcholine as seen by the appearance of a new endothermic peak at 41 degrees (58 degrees). Similarly, in mixed (dipalmitoyl) phosphatidic acid-phosphatidylcholine (2:1) dispersions, Ca2+ again can separate the phosphatidylcholine component."}
{"id": "PMID:234018", "title": "Further studies on the subunit structure of Chromatium ribulose-1,5-phosphate carboxylase.", "content": "Upon alkali exposure Chromatium ribulose-1,5-bisphosphate carboxylase dissociates into constituent subunits, a catalytic oligomer of the larger subunit, A8, and monomeric form of the small subunit B. By sedimentation equilibrium molecular weights of the native enzyme and the catalytic oligomer produced by an alkali treatment were estimated to be 5.11 x 10 5 and 4.29 x 10 5, respectively. To provide information on reversibility of the dissociation by determining whether the enzymically inactive small subunit B of the whole enzyme molecule did indeed exchange with exogenously added subunit B a radioisotopic method was used. After initial alkaline dialysis at pH 9.2 of a mixture of a nonlabeled native enzyme preparation and 14C-labeled subunit B, and the subsequent dialysis at pH 7.0, incorporation of 14C into the recovered native enzyme was determined. Without the alkaline treatment there was no detectable exchange, while after alkaline dialysis for 5 and 10 hr the subunit B exchange was 89 and 82%, respectively. Rabbit antiserum prepared against the catalytic oligomer of the spinach ribulose-1,5-bisphosphate carboxylase, anti-(A) (spinach), inhibited the Chromatium carboxylase and oxygenase activities. This result together with the identical immunoprecipitation lines on an agar plate formed between the antiserum and the Chromatium carboxylase and between the antiserum and the catalytic subunit of the Chromatium enzyme strongly indicated structural near identity of the catalytic subunits of the spinach and Chromatium carboxylase molecules. Results also show that the catalytic site of the Chromatium ribulose-1,5-bisphosphate carboxylase and oxygenase exists in the large polypeptide chain.", "contents": "Further studies on the subunit structure of Chromatium ribulose-1,5-phosphate carboxylase. Upon alkali exposure Chromatium ribulose-1,5-bisphosphate carboxylase dissociates into constituent subunits, a catalytic oligomer of the larger subunit, A8, and monomeric form of the small subunit B. By sedimentation equilibrium molecular weights of the native enzyme and the catalytic oligomer produced by an alkali treatment were estimated to be 5.11 x 10 5 and 4.29 x 10 5, respectively. To provide information on reversibility of the dissociation by determining whether the enzymically inactive small subunit B of the whole enzyme molecule did indeed exchange with exogenously added subunit B a radioisotopic method was used. After initial alkaline dialysis at pH 9.2 of a mixture of a nonlabeled native enzyme preparation and 14C-labeled subunit B, and the subsequent dialysis at pH 7.0, incorporation of 14C into the recovered native enzyme was determined. Without the alkaline treatment there was no detectable exchange, while after alkaline dialysis for 5 and 10 hr the subunit B exchange was 89 and 82%, respectively. Rabbit antiserum prepared against the catalytic oligomer of the spinach ribulose-1,5-bisphosphate carboxylase, anti-(A) (spinach), inhibited the Chromatium carboxylase and oxygenase activities. This result together with the identical immunoprecipitation lines on an agar plate formed between the antiserum and the Chromatium carboxylase and between the antiserum and the catalytic subunit of the Chromatium enzyme strongly indicated structural near identity of the catalytic subunits of the spinach and Chromatium carboxylase molecules. Results also show that the catalytic site of the Chromatium ribulose-1,5-bisphosphate carboxylase and oxygenase exists in the large polypeptide chain."}
{"id": "PMID:234019", "title": "Cobalt and ruthenium replacement for iron in adrenal iron-sulfur protein (adrenodoxin). Preparation and some properties.", "content": "The Co- and Ru-substituted derivatives of adrenal iron-sulfur protein (adrenodoxin) were prepared from its apoprotein in the presence of urea, dithiothreitol, Na2S, and metal ions. Both metal-substituted proteins had 2 g-atoms each of metal and labile sulfur per mole of protein. The Co derivative had optical absorption maxima at 257, 264, 470, and 1430 nm with shoulders at 275, 280, 300, and 380 nm. The molar extinction coefficient per Co atom was 2.200 M-1 cm-1 at 470 nm. The Ru derivative had a broad maximum at 500 nm with a molar extinction coefficient of approximately 100 M-1 cm-1 per Ru atom. The visible chromophore of the Co- and Ru-substituted proteins with mercurials revealed that the saturation levels are 8.6 and 8.4 mol of mercurial/mol of protein. The values agree with that of the native protein within experimental errors. The tyrosyl residue at position 82 displayed a broad anomalous emission at 335 and 331 nm for the Co- and Ru-substituted proteins, respectively, as well as in the case of the native protein. There was no electron paramagnetic resonance signal of the Co derivative in a wide magnetic field at 77 degrees K. Additionally, the Co and Ru derivatives had no enzymatic activity toward NADPH-cytochrome c reduction in the presence of adrenal diaphorase (adrenodoxin reductase). There was no indication that Mn, Ni, Cu, and Os are incorporated into the apoprotein in the presence of urea. Incorporation of Fe into the protein was examined in the presence of Co or Ru. In a system containing both Fe and Ru, Fe was exclusively incorporated into the protein. In contrast to this, the reaction products from a system containing both Fe and Co were found to consist of both Fe and Co derivatives at approximately equimolar quantity.", "contents": "Cobalt and ruthenium replacement for iron in adrenal iron-sulfur protein (adrenodoxin). Preparation and some properties. The Co- and Ru-substituted derivatives of adrenal iron-sulfur protein (adrenodoxin) were prepared from its apoprotein in the presence of urea, dithiothreitol, Na2S, and metal ions. Both metal-substituted proteins had 2 g-atoms each of metal and labile sulfur per mole of protein. The Co derivative had optical absorption maxima at 257, 264, 470, and 1430 nm with shoulders at 275, 280, 300, and 380 nm. The molar extinction coefficient per Co atom was 2.200 M-1 cm-1 at 470 nm. The Ru derivative had a broad maximum at 500 nm with a molar extinction coefficient of approximately 100 M-1 cm-1 per Ru atom. The visible chromophore of the Co- and Ru-substituted proteins with mercurials revealed that the saturation levels are 8.6 and 8.4 mol of mercurial/mol of protein. The values agree with that of the native protein within experimental errors. The tyrosyl residue at position 82 displayed a broad anomalous emission at 335 and 331 nm for the Co- and Ru-substituted proteins, respectively, as well as in the case of the native protein. There was no electron paramagnetic resonance signal of the Co derivative in a wide magnetic field at 77 degrees K. Additionally, the Co and Ru derivatives had no enzymatic activity toward NADPH-cytochrome c reduction in the presence of adrenal diaphorase (adrenodoxin reductase). There was no indication that Mn, Ni, Cu, and Os are incorporated into the apoprotein in the presence of urea. Incorporation of Fe into the protein was examined in the presence of Co or Ru. In a system containing both Fe and Ru, Fe was exclusively incorporated into the protein. In contrast to this, the reaction products from a system containing both Fe and Co were found to consist of both Fe and Co derivatives at approximately equimolar quantity."}
{"id": "PMID:234022", "title": "Diabetic crises in children treated with small doses of intramuscular insulin.", "content": "A new regimen for the management of diabetic crises in children using small doses of intramuscular insulin and generous amounts of intravenous fluids has been devised. Insulin dosage was calculated from the patient's weight and was independent of the degree of hyperglycaemia. Minimum demands were made upon the laboratory.", "contents": "Diabetic crises in children treated with small doses of intramuscular insulin. A new regimen for the management of diabetic crises in children using small doses of intramuscular insulin and generous amounts of intravenous fluids has been devised. Insulin dosage was calculated from the patient's weight and was independent of the degree of hyperglycaemia. Minimum demands were made upon the laboratory."}
{"id": "PMID:234024", "title": "Vascular responses to anaesthetic agents.", "content": "Data have been presented showing that certain general anaesthetic agents such as halothane decrease the spontaneous activity of the rabbit anterior mesenteric portal vein and decrease the response of venous and aortic strips to exogenous noradrenaline. If these observations can be extrapolated to the intact animal they may indicate that the hypotension occurring with use of such agents may be due not only to cardiac effects but also to peripheral vasodilatation and muting of reflex sympathetic vasoconstriction. Although the response to noradrenaline is antagonized, this appears to be nonspecific effect and no evidence was found for interference with noradrenaline release nor for direct actions on beta-adrenegic receptors. While the thiobarbiturates increased spontaneous activity and tone of the rabbit anterior portal vein no evidence was obtained that this occurred through release of noradrenaline from tissue stores.", "contents": "Vascular responses to anaesthetic agents. Data have been presented showing that certain general anaesthetic agents such as halothane decrease the spontaneous activity of the rabbit anterior mesenteric portal vein and decrease the response of venous and aortic strips to exogenous noradrenaline. If these observations can be extrapolated to the intact animal they may indicate that the hypotension occurring with use of such agents may be due not only to cardiac effects but also to peripheral vasodilatation and muting of reflex sympathetic vasoconstriction. Although the response to noradrenaline is antagonized, this appears to be nonspecific effect and no evidence was found for interference with noradrenaline release nor for direct actions on beta-adrenegic receptors. While the thiobarbiturates increased spontaneous activity and tone of the rabbit anterior portal vein no evidence was obtained that this occurred through release of noradrenaline from tissue stores."}
{"id": "PMID:234025", "title": "Concentration of lidocaine hydrochloride in newborn gastric fluid after elective caesarean section and vaginal delivery with epidural analgesia.", "content": "Lidocaine concentrations were measured after vaginal delivery or Caesarean section with epidural anaesthesia in samples of maternal and umbilical blood and in newborn gastric contents. The pH of the gastric aspirate was also determined in a number of neonates. Gastric lidocaine concentrations were higher and the pH was lower after vaginal delivery in comparison to Caesarean section. A significant inverse correlation exists between gastric pH and gastric lidocaine concentration, Neonate gastric lidocaine concentration  was significantly higher than in maternal or umbilical venous plasma after vaginal delivery, but not after Caesarean section. Due to these differences, gastric lavage for the treatment of neonatal lidocaine intoxication may be more beneficial in reducing foetal systemic local anaesthetic concentration after vaginal than after elective abdominal delivery.", "contents": "Concentration of lidocaine hydrochloride in newborn gastric fluid after elective caesarean section and vaginal delivery with epidural analgesia. Lidocaine concentrations were measured after vaginal delivery or Caesarean section with epidural anaesthesia in samples of maternal and umbilical blood and in newborn gastric contents. The pH of the gastric aspirate was also determined in a number of neonates. Gastric lidocaine concentrations were higher and the pH was lower after vaginal delivery in comparison to Caesarean section. A significant inverse correlation exists between gastric pH and gastric lidocaine concentration, Neonate gastric lidocaine concentration  was significantly higher than in maternal or umbilical venous plasma after vaginal delivery, but not after Caesarean section. Due to these differences, gastric lavage for the treatment of neonatal lidocaine intoxication may be more beneficial in reducing foetal systemic local anaesthetic concentration after vaginal than after elective abdominal delivery."}
{"id": "PMID:234028", "title": "Pharmacokinetic mechanisms of drug interactions.", "content": "Many patients require multiple-drug therapy, often under the supervision of several physicians, this increasing the risk of adverse drug effects. While drug interactions cannot always be conveniently categorized, familiarity with basic pharmacologic and pharmacokinetic principles permits the clinician to anticipate and avoid many of the more common and serious drug interactions. Most serious drug interactions involve one of the four pharmacokinetic processes governing drug behavior within the body: absorption, distribution, metabolism, and renal clearance. Knowledge of whether a drug is a weak acid or a weak base is clinically useful because it can alert the physician to the propensity for certain types of drug interactions.", "contents": "Pharmacokinetic mechanisms of drug interactions. Many patients require multiple-drug therapy, often under the supervision of several physicians, this increasing the risk of adverse drug effects. While drug interactions cannot always be conveniently categorized, familiarity with basic pharmacologic and pharmacokinetic principles permits the clinician to anticipate and avoid many of the more common and serious drug interactions. Most serious drug interactions involve one of the four pharmacokinetic processes governing drug behavior within the body: absorption, distribution, metabolism, and renal clearance. Knowledge of whether a drug is a weak acid or a weak base is clinically useful because it can alert the physician to the propensity for certain types of drug interactions."}
{"id": "PMID:234029", "title": "Oxidizing action of purine N-oxide esters.", "content": "A technique involving O-acetylation of purine N-oxide derivatives in buffered aqueous solutions has permitted studies of the reactivity of many compounds for which the O-acetyl derivatives are not otherwise available. The oxidizing properties of a variety of N-acetoxypurines have been measured through their ability to oxidize iodide ion ot iodine, a reaction which is representative of a more general oxidizing ability. Those esters that oxidize iodide ion also catalyze the autoxidation of sulfite, a property characteristic of radicals. The same esters also oxidize cysteine to cysteic acid and tryptophan, tyrosine, and uric acid to yet uncharacterized products. Their oxidizing reactivity was compared with the ability of the same esters to react as electrophiles in another assay that measured the rate of formation of pyridine substitution products. The sulfate ester of 3-hydroxyxanthine has been synthesized. Its reactivity is qualitatively the same as that of 3-acetoxyxanthine but proceeds at a higher rate. Syntheses of S-(8-xanthyl)-N-acetylcysteine,  8-(2-hydroxyethylthio)xanthine,  and 1-methyl-8-mehtylmercaptoguanine are also described.", "contents": "Oxidizing action of purine N-oxide esters. A technique involving O-acetylation of purine N-oxide derivatives in buffered aqueous solutions has permitted studies of the reactivity of many compounds for which the O-acetyl derivatives are not otherwise available. The oxidizing properties of a variety of N-acetoxypurines have been measured through their ability to oxidize iodide ion ot iodine, a reaction which is representative of a more general oxidizing ability. Those esters that oxidize iodide ion also catalyze the autoxidation of sulfite, a property characteristic of radicals. The same esters also oxidize cysteine to cysteic acid and tryptophan, tyrosine, and uric acid to yet uncharacterized products. Their oxidizing reactivity was compared with the ability of the same esters to react as electrophiles in another assay that measured the rate of formation of pyridine substitution products. The sulfate ester of 3-hydroxyxanthine has been synthesized. Its reactivity is qualitatively the same as that of 3-acetoxyxanthine but proceeds at a higher rate. Syntheses of S-(8-xanthyl)-N-acetylcysteine,  8-(2-hydroxyethylthio)xanthine,  and 1-methyl-8-mehtylmercaptoguanine are also described."}
{"id": "PMID:234030", "title": "Cyclic adenosine 3':5'-monophosphate phosphodiesterase activity in malignant and cyclic adenosine 3':5'-monophosphate-induced \"differentiated\" neuroblastoma cells.", "content": "The regulation of cyclic adenosine 3:5-monophosphate (cyclic AMP) phosphodiesterase activity in homogenates of malignant and cyclic AMP-induced \"differentiated\" neuroblastoma cells was studied. Neuroblastoma cells of at least three mouse and one human clone had both the low (2 to 4 muM) and the high (66 to 106 muM) Km phosphodiesterase. In cyclic AMP-induced differentiated cells the values of Km were decreased, whereas the values of Vmax appeared to be slightly increased. Magnesium and manganese stimulated phosphodiesterase activity. Calcium, zinc, copper, mercury, ethylenediaminetetraacetic acid, and imidazole completely inhibited phosphodiesterase activity in malignant cells, whereas the above agents, except ethylenediaminetetraacetic acid, only partially inhibited enzyme activity in differentiated cells. Ethylenediaminetetraacetic acid completely reduced phosphodiesterase activity in differentiated cells. The pH optimum for phosphodiesterase activity was about 8 in both malignant and differentiated cells. The present studies show that the values of Km and Vmax and the sensitivity of phosphodiesterase activity to divalent ions change in cyclic AMP-induced differentiated neuroblastoma cells, and therefore we propose that the reverse may be true during malignant transformation of nerve cells.", "contents": "Cyclic adenosine 3':5'-monophosphate phosphodiesterase activity in malignant and cyclic adenosine 3':5'-monophosphate-induced \"differentiated\" neuroblastoma cells. The regulation of cyclic adenosine 3:5-monophosphate (cyclic AMP) phosphodiesterase activity in homogenates of malignant and cyclic AMP-induced \"differentiated\" neuroblastoma cells was studied. Neuroblastoma cells of at least three mouse and one human clone had both the low (2 to 4 muM) and the high (66 to 106 muM) Km phosphodiesterase. In cyclic AMP-induced differentiated cells the values of Km were decreased, whereas the values of Vmax appeared to be slightly increased. Magnesium and manganese stimulated phosphodiesterase activity. Calcium, zinc, copper, mercury, ethylenediaminetetraacetic acid, and imidazole completely inhibited phosphodiesterase activity in malignant cells, whereas the above agents, except ethylenediaminetetraacetic acid, only partially inhibited enzyme activity in differentiated cells. Ethylenediaminetetraacetic acid completely reduced phosphodiesterase activity in differentiated cells. The pH optimum for phosphodiesterase activity was about 8 in both malignant and differentiated cells. The present studies show that the values of Km and Vmax and the sensitivity of phosphodiesterase activity to divalent ions change in cyclic AMP-induced differentiated neuroblastoma cells, and therefore we propose that the reverse may be true during malignant transformation of nerve cells."}
{"id": "PMID:234031", "title": "Microsomal metabolism of nitrosoureas.", "content": "N, N-Bis (2-chloroethyl)-N-nitrosourea (BCNU) is a substrate for a microsomal enzyme of mouse liver. The reaction requires NADPH, and the product is 1, 3-bis (2-chloroethyl) urea. This activity is also found in mouse lungs but not in several other tissues. With reaction conditions under which BCNU is not chemically degraded, the Km for BCNU with liver microsomes is 1.7 mM; nicotine is a competitive inhibitor with a Ki of 0.6 mM. N-Methyl-N-nitrosourea is denitrosated in a similar reaction. N- (2-Chloroetyhy)- N-cyclohexyl-N-nitrosourea and N-(2-chloroethyl)-N-(trans-4-methylcyclohexyl)-N-nitrosourea are also substrates for microsomal enzymes, but the products of these reactions are ring-hydroxylated derivatives. The Km value for N-(2-CHLOROETHYL)-N-cyclohexyl-N-nitrosourea is 3.0 mM and that for N-(2-chloroethyl)-N-(trans-4-methylcyclohexyl)-N-nitrosourea is 1.0 mM. The hydroxylase activity is also present in lungs, but not in the other mouse tissues. The rates of microsomal metabolism of BCNU, N-(2-chloroethyl)-N-cyclohexyl-N-nitrosourea, and N-(2-chloroethyl)-N-cyclohexyl-N-nitrosourea, and N-(2-chloroethyl-N-(trans-4-methylcyclohexyl)-N-nitrosourea are fast enough to allow metabolism of large portions of administered doses before chemical decomposition of the drugs occurs.", "contents": "Microsomal metabolism of nitrosoureas. N, N-Bis (2-chloroethyl)-N-nitrosourea (BCNU) is a substrate for a microsomal enzyme of mouse liver. The reaction requires NADPH, and the product is 1, 3-bis (2-chloroethyl) urea. This activity is also found in mouse lungs but not in several other tissues. With reaction conditions under which BCNU is not chemically degraded, the Km for BCNU with liver microsomes is 1.7 mM; nicotine is a competitive inhibitor with a Ki of 0.6 mM. N-Methyl-N-nitrosourea is denitrosated in a similar reaction. N- (2-Chloroetyhy)- N-cyclohexyl-N-nitrosourea and N-(2-chloroethyl)-N-(trans-4-methylcyclohexyl)-N-nitrosourea are also substrates for microsomal enzymes, but the products of these reactions are ring-hydroxylated derivatives. The Km value for N-(2-CHLOROETHYL)-N-cyclohexyl-N-nitrosourea is 3.0 mM and that for N-(2-chloroethyl)-N-(trans-4-methylcyclohexyl)-N-nitrosourea is 1.0 mM. The hydroxylase activity is also present in lungs, but not in the other mouse tissues. The rates of microsomal metabolism of BCNU, N-(2-chloroethyl)-N-cyclohexyl-N-nitrosourea, and N-(2-chloroethyl)-N-cyclohexyl-N-nitrosourea, and N-(2-chloroethyl-N-(trans-4-methylcyclohexyl)-N-nitrosourea are fast enough to allow metabolism of large portions of administered doses before chemical decomposition of the drugs occurs."}
{"id": "PMID:234032", "title": "The relationship between metabolism, DNA binding, and carcinogenicity of 15,16-dihydro-11-methylcyclopenta(alpha)phenanthren-17-one in the presence of a microsomal enzyme inhibitor.", "content": "The mean latent period for skin tumor production by the carcinogen 15, 16-dihydro-11-methylcyclopenta [alpha] phenanthren-17-one (Compound IVb) in the mouse was 30 weeks for a dose of 60 mug/week and about 45 weeks for 60 mug/week, while at 0.6 mug/week, no tumors were observed during 100 weeks. Simultaneous administration of the closely related noncarcinogen (IVa) (54 mug/week) together with the carcinogen at 60 mug/week had no effect on the mean latent period. Simultaneous administration of a threefold quantity of the microsomal enzyme inhibitor 7, 8-benzoflavone (I) with the carcinogen at the highest dose increased the mean latent period to 38 weeks, while at the intermediate dose it completely suppressed tumor formation. Neither ketone IVa nor IVb bound covalently to calf thymus DNA in vitro without prior metabolic activation. After incubation with rat liver microsomes and NADPH in the presence of air, both ketones bound covalently to added DNA in vitro, the noncarcinogen (IVa) about four times more extensively than the carcinogen (IVb), roughly in proportion to the overall extents to which these ketones were metabolized. In contrast, overall metabolism of the carcinogen (IVb) was somewhat increased by the addition of a threefold quantity of the inhibitor (I) to the incubation mixture, but binding to added DNA was almost completely prevented. These results are discussed in connection with the hypothesis that cellular DNA is the target of the carcinogen (IVb) for tumor initiation.", "contents": "The relationship between metabolism, DNA binding, and carcinogenicity of 15,16-dihydro-11-methylcyclopenta(alpha)phenanthren-17-one in the presence of a microsomal enzyme inhibitor. The mean latent period for skin tumor production by the carcinogen 15, 16-dihydro-11-methylcyclopenta [alpha] phenanthren-17-one (Compound IVb) in the mouse was 30 weeks for a dose of 60 mug/week and about 45 weeks for 60 mug/week, while at 0.6 mug/week, no tumors were observed during 100 weeks. Simultaneous administration of the closely related noncarcinogen (IVa) (54 mug/week) together with the carcinogen at 60 mug/week had no effect on the mean latent period. Simultaneous administration of a threefold quantity of the microsomal enzyme inhibitor 7, 8-benzoflavone (I) with the carcinogen at the highest dose increased the mean latent period to 38 weeks, while at the intermediate dose it completely suppressed tumor formation. Neither ketone IVa nor IVb bound covalently to calf thymus DNA in vitro without prior metabolic activation. After incubation with rat liver microsomes and NADPH in the presence of air, both ketones bound covalently to added DNA in vitro, the noncarcinogen (IVa) about four times more extensively than the carcinogen (IVb), roughly in proportion to the overall extents to which these ketones were metabolized. In contrast, overall metabolism of the carcinogen (IVb) was somewhat increased by the addition of a threefold quantity of the inhibitor (I) to the incubation mixture, but binding to added DNA was almost completely prevented. These results are discussed in connection with the hypothesis that cellular DNA is the target of the carcinogen (IVb) for tumor initiation."}
{"id": "PMID:234033", "title": "Immunochemotherapy of transplantable Moloney leukemia with cyclophosphamide and allogeneic spleen lymphocytes and reversal of graft-versus-host disease with alloantiserum.", "content": "Histoincompatible (H-2) spleen cells from C57BL/6 mice that were sensitized with Moloney sarcoma virus caused fatal graft-versus-host disease in BALB/c mice when the cells were used in conjunction with an immunosuppressive, chemotherapeutic dose of cyclophosphamide to treat transplantable Moloney virus-induced leukemia. When antiserum against the donor spleen cells was administered 2 days after immunochemotherapy, graft-versus-host disease was prevented, but no immunotherapeutic effect was observed. When the antiserum was delayed for 3 days or more, lethal graft-versus-host disease occurred. Substitution of Moloney sarcoma virus-sensitized BALB/c X C57BL/6 F1 (hereafter called CB6F1) spleen cells for C57BL/6 cells, in conjunction with cyclophosphamide, \"cured\" 70% of the treated mice (accumulated value of two experiments). When anti-CB6F1 serum (alloantiserum) was administered 2 days after immunochemotherapy, the immunotherapeutic effect was abolished. Alloantiserum was not able to reverse the immunotherapeutic effect 3 days postgrafting or later, and there resulted a high percentage of long-term survivors. About two-thirds of the cured mice had positive donor-specific gamma-globulin titer 8 weeks postgrafting.", "contents": "Immunochemotherapy of transplantable Moloney leukemia with cyclophosphamide and allogeneic spleen lymphocytes and reversal of graft-versus-host disease with alloantiserum. Histoincompatible (H-2) spleen cells from C57BL/6 mice that were sensitized with Moloney sarcoma virus caused fatal graft-versus-host disease in BALB/c mice when the cells were used in conjunction with an immunosuppressive, chemotherapeutic dose of cyclophosphamide to treat transplantable Moloney virus-induced leukemia. When antiserum against the donor spleen cells was administered 2 days after immunochemotherapy, graft-versus-host disease was prevented, but no immunotherapeutic effect was observed. When the antiserum was delayed for 3 days or more, lethal graft-versus-host disease occurred. Substitution of Moloney sarcoma virus-sensitized BALB/c X C57BL/6 F1 (hereafter called CB6F1) spleen cells for C57BL/6 cells, in conjunction with cyclophosphamide, \"cured\" 70% of the treated mice (accumulated value of two experiments). When anti-CB6F1 serum (alloantiserum) was administered 2 days after immunochemotherapy, the immunotherapeutic effect was abolished. Alloantiserum was not able to reverse the immunotherapeutic effect 3 days postgrafting or later, and there resulted a high percentage of long-term survivors. About two-thirds of the cured mice had positive donor-specific gamma-globulin titer 8 weeks postgrafting."}
{"id": "PMID:234034", "title": "In vitro metabolic conversion of aflatoxins and benzo(alpha)pyrene to nucleic acid-binding metabolites.", "content": "An aflatoxin B1 metabolite was found to become covalently bound to rat liver RNA and calf thymus DNA in vitro, and it formed complexes with increased spectral absorbance in the 360 nm region. The formation of such complexes was reduced nicotinamide adenine dinucleotide phosphate and microsome dependent, was inhibited by theta-diethylaminoethyl diphenylpropylacetate-HC1, and by CO and N2, when the latter were used to replace the gas phase of the incubations. The formation of the complexes was enhanced about 2-fold with cicrosomes from phenobarbital-treated rats but not from 3-methylcholanthrene-treated rats. More binding was observed with DNA than RNA. Dentured DNA was about 70% as effective as native DNA. Nucleic acids from various sources showed the following order of binding potency: DNA from Micrococcus luteus greater than DNA from calf thymus equal to DNA from rat liver greater than RNA from rat liver greater than transfer RNA from rat liver. In the presence of reduced nicotinamide adenine dinucleotide phosphate and microsomes from phenobarbital-treated rats, aflatoxin G1 was also converted into metabolite(s) that became covalently bound to nucleic acids and formed complexes with increased spectral absorbances in the 360 nm region: this reaction was also inhibited by theta-diethylaminoethyl diphenylpropylacetate-HC1. Under the same conditions, aflatoxin B2, aflatoxin G2, aflatoxin B2a, and \"Compound 11,\" which lack a C2-C3 double bond, did not show any noticeable binding to either DNA or RNA. These data strongly support the concept that the microsomal mixed-funciton oxygenase-catalyzed oxidation of the C2-C3 double bond of aflatoxins is a prerequisite for the formation of nucleic acid-binding metabolites. Microsomes from untreated, phenobarbital-treated, and 3-methylcholanthrene-treated rats were compared in vitro for their ability to catalyze the formation of DNA-binding metabolites from aflatozin B1 and benzo(a)pyrene. In assays involving benzo(a)pyrene, microsomes from 3-methylcholanthrene-treated rats were 12- and 5-fold more active than microsomes from untreated and phenobar-bital-treated rats, respectively. This is in contrast to the results obtained with aflatoxin B1 and suggests that different enzymes in the hepatic microsomal mixed-function oxygenase complex are involved in the generation of reactive metabolites from various polycyclic hydrocarbons.", "contents": "In vitro metabolic conversion of aflatoxins and benzo(alpha)pyrene to nucleic acid-binding metabolites. An aflatoxin B1 metabolite was found to become covalently bound to rat liver RNA and calf thymus DNA in vitro, and it formed complexes with increased spectral absorbance in the 360 nm region. The formation of such complexes was reduced nicotinamide adenine dinucleotide phosphate and microsome dependent, was inhibited by theta-diethylaminoethyl diphenylpropylacetate-HC1, and by CO and N2, when the latter were used to replace the gas phase of the incubations. The formation of the complexes was enhanced about 2-fold with cicrosomes from phenobarbital-treated rats but not from 3-methylcholanthrene-treated rats. More binding was observed with DNA than RNA. Dentured DNA was about 70% as effective as native DNA. Nucleic acids from various sources showed the following order of binding potency: DNA from Micrococcus luteus greater than DNA from calf thymus equal to DNA from rat liver greater than RNA from rat liver greater than transfer RNA from rat liver. In the presence of reduced nicotinamide adenine dinucleotide phosphate and microsomes from phenobarbital-treated rats, aflatoxin G1 was also converted into metabolite(s) that became covalently bound to nucleic acids and formed complexes with increased spectral absorbances in the 360 nm region: this reaction was also inhibited by theta-diethylaminoethyl diphenylpropylacetate-HC1. Under the same conditions, aflatoxin B2, aflatoxin G2, aflatoxin B2a, and \"Compound 11,\" which lack a C2-C3 double bond, did not show any noticeable binding to either DNA or RNA. These data strongly support the concept that the microsomal mixed-funciton oxygenase-catalyzed oxidation of the C2-C3 double bond of aflatoxins is a prerequisite for the formation of nucleic acid-binding metabolites. Microsomes from untreated, phenobarbital-treated, and 3-methylcholanthrene-treated rats were compared in vitro for their ability to catalyze the formation of DNA-binding metabolites from aflatozin B1 and benzo(a)pyrene. In assays involving benzo(a)pyrene, microsomes from 3-methylcholanthrene-treated rats were 12- and 5-fold more active than microsomes from untreated and phenobar-bital-treated rats, respectively. This is in contrast to the results obtained with aflatoxin B1 and suggests that different enzymes in the hepatic microsomal mixed-function oxygenase complex are involved in the generation of reactive metabolites from various polycyclic hydrocarbons."}
{"id": "PMID:234035", "title": "Tumor rejection in experimental animals treated with radioprotective thiols.", "content": "In experimental animals, a systemic treatment with thiols of the mercaptoalkylamine type has affected all of five solid tumors so far investigated. (Three of the tumors were transplanted into the strain of origin.) There was either inhibition of growth or \"oncodieresis,\" i.e., a necrosis and sloughing of tumors conducive to full recovery and repair. Mercaptoalkylamines and derivatives of the type used in our experiments are known to bind to cellular sites by a two-point attachment involving both thiol and amino groups. One of these compounds, cysteamine, was active in its native, unsubstituted form, but did not bring about oncodieresis when either the amino or thiol group, or both, were alkylated. Mercaptopropylamine, the 3-carbon homolog of cysteamine, was less active. Cystamine, a disulfide dimer of cysteamine that has no free reactive  sulfhydryl, did not induce any reaction. Thioglycerol, lacking a terminal amino group, had only negligible activity. Rejection was much more striking when treatment was started on the day of inoculation than when started 7 days later. Male mice rejected better than females. Results were inferior when tow of the agents were given simultaneously or together with other radioprotectants, such as L-cysteine, glutathione, dimethyl sulfoxide, or reserpine. Tumor rejection was enhanced when the phosphorylated thioyls, S-2-(3-aminopropylamino)ethylphosphorothioic acid or S-(2-ethylguanidine)phosphorothioci acid, were given simultaneously with the radioprotective serotonin, but there was no synergy of serotonin with the nonphosphorylated compounds S-2-aminoethylisothiouronium bromide or cysteamine. Serotonin alone did not affect the tumors.", "contents": "Tumor rejection in experimental animals treated with radioprotective thiols. In experimental animals, a systemic treatment with thiols of the mercaptoalkylamine type has affected all of five solid tumors so far investigated. (Three of the tumors were transplanted into the strain of origin.) There was either inhibition of growth or \"oncodieresis,\" i.e., a necrosis and sloughing of tumors conducive to full recovery and repair. Mercaptoalkylamines and derivatives of the type used in our experiments are known to bind to cellular sites by a two-point attachment involving both thiol and amino groups. One of these compounds, cysteamine, was active in its native, unsubstituted form, but did not bring about oncodieresis when either the amino or thiol group, or both, were alkylated. Mercaptopropylamine, the 3-carbon homolog of cysteamine, was less active. Cystamine, a disulfide dimer of cysteamine that has no free reactive  sulfhydryl, did not induce any reaction. Thioglycerol, lacking a terminal amino group, had only negligible activity. Rejection was much more striking when treatment was started on the day of inoculation than when started 7 days later. Male mice rejected better than females. Results were inferior when tow of the agents were given simultaneously or together with other radioprotectants, such as L-cysteine, glutathione, dimethyl sulfoxide, or reserpine. Tumor rejection was enhanced when the phosphorylated thioyls, S-2-(3-aminopropylamino)ethylphosphorothioic acid or S-(2-ethylguanidine)phosphorothioci acid, were given simultaneously with the radioprotective serotonin, but there was no synergy of serotonin with the nonphosphorylated compounds S-2-aminoethylisothiouronium bromide or cysteamine. Serotonin alone did not affect the tumors."}
{"id": "PMID:234078", "title": "Testosterone 5alpha-reductase in rat skin homogenates: measurement in the skin at various anatomical sites in males and females.", "content": "Experiments were disigned to find suitable conditions to determine the  5alpha-reducatase activity in rat skin homogenates. The dihydrotestosterone formation was linear until 15 min. The 5alpha- reductase was very heat labile at 37-c in absence of testosterone and NADPH since complete loss of activity occurred after one hour of preincubation. At OC, there was a 20% decrease after 5 hr. The enzyme activiity was measured in the skin at various anatomical sites. It was found to vary with each region in the following order in the male; tail,greater than scrotum greater than ear greater than genital skin greater than dorsum smaller than or equal to thorax greater than sole of the foot. In a few tissues, the enzyme activity was higher than in the prostate. Corresponding female tissues exhibited lower reductase activity except the sole of the foot in which the contrary was found. This significant sex difference indicates that sex hormones may be involved in the control of the levels of that enzyme in rat skin.", "contents": "Testosterone 5alpha-reductase in rat skin homogenates: measurement in the skin at various anatomical sites in males and females. Experiments were disigned to find suitable conditions to determine the  5alpha-reducatase activity in rat skin homogenates. The dihydrotestosterone formation was linear until 15 min. The 5alpha- reductase was very heat labile at 37-c in absence of testosterone and NADPH since complete loss of activity occurred after one hour of preincubation. At OC, there was a 20% decrease after 5 hr. The enzyme activiity was measured in the skin at various anatomical sites. It was found to vary with each region in the following order in the male; tail,greater than scrotum greater than ear greater than genital skin greater than dorsum smaller than or equal to thorax greater than sole of the foot. In a few tissues, the enzyme activity was higher than in the prostate. Corresponding female tissues exhibited lower reductase activity except the sole of the foot in which the contrary was found. This significant sex difference indicates that sex hormones may be involved in the control of the levels of that enzyme in rat skin."}
{"id": "PMID:234118", "title": "Recurrent keratitis due to Acremonium potronii.", "content": "In a 15-year-old boy a culture-proved keratitis after a corneal perforation healed without antifungal agents after corneal suturing and application of tissue glue. Eight months later a posterior corneal abscess developed. Diagnostic and therapeutic penetrating keratoplasty was performed when the lesion failed to respond to pimaricin. Cultures were positive for Acremonium potronii, the same fungus isolated from the original corneal laceration eight months previously. To our acknowledge, this is the first case report of a central corneal ulcer or abscess due to this specific organism.", "contents": "Recurrent keratitis due to Acremonium potronii. In a 15-year-old boy a culture-proved keratitis after a corneal perforation healed without antifungal agents after corneal suturing and application of tissue glue. Eight months later a posterior corneal abscess developed. Diagnostic and therapeutic penetrating keratoplasty was performed when the lesion failed to respond to pimaricin. Cultures were positive for Acremonium potronii, the same fungus isolated from the original corneal laceration eight months previously. To our acknowledge, this is the first case report of a central corneal ulcer or abscess due to this specific organism."}
{"id": "PMID:234121", "title": "Splanchnic hemodynamic response to passive hyperventilation.", "content": "Two groups of anesthetized, splenectomized, and paralyzed dogs were hyperventilated (Vt 40 ml/kg). Normocapnia was maintained in one group (mean Paco2 37.6 mm\"h'g, mean p\"h '7.41) and respiratory alkalosis (mean Paco2 8 mmHg, mean pH 7.75) in the other. Splanchnic hemodynamic responses were similar in both groups. Average hepatic venous pressure increased from 3.2 to 6.4 mmHg in the normocapnic group and from 3.8 to 7.7 mmHg in the hypocapnic group. Average portal venous pressure increased from 10.7 to 12.0 mmHg and 10.8 to 12.7 mmHg in the normocapnic and hypocapnic groups, respectively. Mesenteric vascular resistance increased in 93 per cent of dogs. A decrease in functional intestinal capillary surface area during hyperventilation was indicated by a significant reduction in mesenteric Vo2 (from 15 to 11 ml/min, average 30 per cent), and a concomitant reduction in mesenteric O2 extraction ratio. Changes in mesenteric Vo2 were reflected in calculated splanchinic Vo2. Hepatic O2 uptake was essentially unchanged by tidal hyperventilation with or without hypocapnia.", "contents": "Splanchnic hemodynamic response to passive hyperventilation. Two groups of anesthetized, splenectomized, and paralyzed dogs were hyperventilated (Vt 40 ml/kg). Normocapnia was maintained in one group (mean Paco2 37.6 mm\"h'g, mean p\"h '7.41) and respiratory alkalosis (mean Paco2 8 mmHg, mean pH 7.75) in the other. Splanchnic hemodynamic responses were similar in both groups. Average hepatic venous pressure increased from 3.2 to 6.4 mmHg in the normocapnic group and from 3.8 to 7.7 mmHg in the hypocapnic group. Average portal venous pressure increased from 10.7 to 12.0 mmHg and 10.8 to 12.7 mmHg in the normocapnic and hypocapnic groups, respectively. Mesenteric vascular resistance increased in 93 per cent of dogs. A decrease in functional intestinal capillary surface area during hyperventilation was indicated by a significant reduction in mesenteric Vo2 (from 15 to 11 ml/min, average 30 per cent), and a concomitant reduction in mesenteric O2 extraction ratio. Changes in mesenteric Vo2 were reflected in calculated splanchinic Vo2. Hepatic O2 uptake was essentially unchanged by tidal hyperventilation with or without hypocapnia."}
{"id": "PMID:234122", "title": "Blood P50 calculated from a single measurement of pH, PO2, and SO2.", "content": "P50 was calculated from a single measurement of pH, Po2, and So2 at a known temperature in 135 blood samples from 21 normal nonsmokers and eight patients. In the 92 blood samples with So2 between 20 and 90 per cent, the standard deviation of repeated calculated P50's on the same sample of blood at different So2 was plus or minus 1.0 Torr. Below So2 of 20 per cent and above So2 of 90 per cent, the standard deviations were plus or minus 5.5 and plus or minus 2.4 Torr, respectively. Combined measurement errors of plus or minus 1 Torr in Po2, plus or minus 1 percent in So2, plus or minus 0.01 in pH, and plus or minus 0.1 degree C in temperature are sufficient to explain the observed variation in calculated P50 in 90 per cent of 135 blood samples from 29 subjects and account for the greater observed variation at So2 less than 20 per cent and greater than 90 per cent.", "contents": "Blood P50 calculated from a single measurement of pH, PO2, and SO2. P50 was calculated from a single measurement of pH, Po2, and So2 at a known temperature in 135 blood samples from 21 normal nonsmokers and eight patients. In the 92 blood samples with So2 between 20 and 90 per cent, the standard deviation of repeated calculated P50's on the same sample of blood at different So2 was plus or minus 1.0 Torr. Below So2 of 20 per cent and above So2 of 90 per cent, the standard deviations were plus or minus 5.5 and plus or minus 2.4 Torr, respectively. Combined measurement errors of plus or minus 1 Torr in Po2, plus or minus 1 percent in So2, plus or minus 0.01 in pH, and plus or minus 0.1 degree C in temperature are sufficient to explain the observed variation in calculated P50 in 90 per cent of 135 blood samples from 29 subjects and account for the greater observed variation at So2 less than 20 per cent and greater than 90 per cent."}
{"id": "PMID:234123", "title": "Oxygen delivery and utilization in dogs with a sublethal dose of cobalt chloride.", "content": "Four groups of eight dogs each were anesthetized with pentobarbital, paralyzed with succinylcholine, and ventilated at constant rate. Control measurements were made for 30 min, then 15 mg/kg of cobaltous chloride was given slowly intravenously to one group. A second group was also given 1 mg/kg per h propranolol (beta-block); a third group was given NaHCO3 to correct pH changes after CoCl2; and a fourth group had both beta-block and NaHCO3. Vo2 was measured every 10 min for 4 h and blood was taken frequently for lactate, pyruvate, and blood gas measurements. Cobalt transiently decreased Vo2 in all groups but significantly more in those with beta-block (groups 2 and 4). Cardiac output and mean arterial pressure were also decreased in all groups but to similar extent. Recovery of Vo2 was complete, usually within 60 min with little evidence of deficit repayment. Total O2 transport (Q X Cao2) appeared to limit Vo2 below 12 ml/kg times min. Above that value, histotoxic effects of CoCl2 reduced Vo2 approximately 20%. Excess lactate (XL) in arterial blood was linearly correlated with measured O2 deficit during the acute reaction of CoCl2, in all but group 3, similar to results previously obtained in hypoxic hypoxia.", "contents": "Oxygen delivery and utilization in dogs with a sublethal dose of cobalt chloride. Four groups of eight dogs each were anesthetized with pentobarbital, paralyzed with succinylcholine, and ventilated at constant rate. Control measurements were made for 30 min, then 15 mg/kg of cobaltous chloride was given slowly intravenously to one group. A second group was also given 1 mg/kg per h propranolol (beta-block); a third group was given NaHCO3 to correct pH changes after CoCl2; and a fourth group had both beta-block and NaHCO3. Vo2 was measured every 10 min for 4 h and blood was taken frequently for lactate, pyruvate, and blood gas measurements. Cobalt transiently decreased Vo2 in all groups but significantly more in those with beta-block (groups 2 and 4). Cardiac output and mean arterial pressure were also decreased in all groups but to similar extent. Recovery of Vo2 was complete, usually within 60 min with little evidence of deficit repayment. Total O2 transport (Q X Cao2) appeared to limit Vo2 below 12 ml/kg times min. Above that value, histotoxic effects of CoCl2 reduced Vo2 approximately 20%. Excess lactate (XL) in arterial blood was linearly correlated with measured O2 deficit during the acute reaction of CoCl2, in all but group 3, similar to results previously obtained in hypoxic hypoxia."}
{"id": "PMID:234124", "title": "Effect of positive-pressure breathing on aADN2 in hyaline membrane disease.", "content": "In seven subjects with hyaline membrane disease and breathing 40-70% oxygen in nitrogen, the effect of continuous positive-pressure breathing (CPPB) was examined by application of a continuous negative pressure (10 cm water) about the thorax and assessment of the alveolar-arterial tension differences for nitrogen (aADn2) and oxygen (AaDo2). On CPPB, there was a decrease in the aADn2 by a mean 9 mmHg and a decrease in the AaDo2 by a mean 44 mmHg. This corresponded to a decrease in the total venous admixture (Qva/Qt) of 0.20 and to a decrease in the venous admixture due to a true right-to-left shunt (Qs/Qt) of 0.19. These data were interpreted to mean a significant improvement in Va/Qc imbalance within open ventilated parts of the lung, which could be responsible, particularly by relief of local alveolar hypoxia, for reduction of the pulmonary vascular resistance and the true right-to-left shunt.", "contents": "Effect of positive-pressure breathing on aADN2 in hyaline membrane disease. In seven subjects with hyaline membrane disease and breathing 40-70% oxygen in nitrogen, the effect of continuous positive-pressure breathing (CPPB) was examined by application of a continuous negative pressure (10 cm water) about the thorax and assessment of the alveolar-arterial tension differences for nitrogen (aADn2) and oxygen (AaDo2). On CPPB, there was a decrease in the aADn2 by a mean 9 mmHg and a decrease in the AaDo2 by a mean 44 mmHg. This corresponded to a decrease in the total venous admixture (Qva/Qt) of 0.20 and to a decrease in the venous admixture due to a true right-to-left shunt (Qs/Qt) of 0.19. These data were interpreted to mean a significant improvement in Va/Qc imbalance within open ventilated parts of the lung, which could be responsible, particularly by relief of local alveolar hypoxia, for reduction of the pulmonary vascular resistance and the true right-to-left shunt."}
{"id": "PMID:234125", "title": "The transport of sulfate ions across the membrane of the Ehrlich ascites tumor cell.", "content": "The applicability of the membrane fixed charge hypothesis to anion transport in Ehrlich ascites tumor cells was studied by investigating the dependence of steady state sulfate transport on the extracellular pH, chloride and sulfate concentration. When the extracellular sulfate was maintained at 10 mM both cellular sulfate and sulfate transport increased with decreasing pH and chloride concentration. The dependence of sulfate transport on the cellular sulfate concentration suggests a saturation phenomenon. The relationship between sulfate transport and cellular sulfate was also studied as a function of extracellular sulfate, both in the presence and absence of chloride. In both cases, sulfate transport is a saturable function of the cellular sulfate. However, in the presence of chloride the maximal flux is twice that in its absence. The discrepancy between the maximal fluxes suggests that the transport system mediates chloride-sulfate exchange in addition to sulfate self exchange. Unidirectional sulfate effluxes into chloride and sulfate-free medium; into 50 mM sulfate medium or 50 mM chloride medium were: 0.38, 1.95 and 3.91 nmoles/10-7 cells min-minus1, respectively. These results indicate that in the absence of either sulfate or chloride the net efflux of sulfate is low. However, chloride or sulfate on the trans side of the membrane is effective in accelerating unidirectional sulfate efflux. Taken together, the results of this investigation cannot be explained in terms of the membrane fixed charge hypothesis. Rather, they support the contention that sulfate transport across the tumor cell membrane is a carrier-mediated process.", "contents": "The transport of sulfate ions across the membrane of the Ehrlich ascites tumor cell. The applicability of the membrane fixed charge hypothesis to anion transport in Ehrlich ascites tumor cells was studied by investigating the dependence of steady state sulfate transport on the extracellular pH, chloride and sulfate concentration. When the extracellular sulfate was maintained at 10 mM both cellular sulfate and sulfate transport increased with decreasing pH and chloride concentration. The dependence of sulfate transport on the cellular sulfate concentration suggests a saturation phenomenon. The relationship between sulfate transport and cellular sulfate was also studied as a function of extracellular sulfate, both in the presence and absence of chloride. In both cases, sulfate transport is a saturable function of the cellular sulfate. However, in the presence of chloride the maximal flux is twice that in its absence. The discrepancy between the maximal fluxes suggests that the transport system mediates chloride-sulfate exchange in addition to sulfate self exchange. Unidirectional sulfate effluxes into chloride and sulfate-free medium; into 50 mM sulfate medium or 50 mM chloride medium were: 0.38, 1.95 and 3.91 nmoles/10-7 cells min-minus1, respectively. These results indicate that in the absence of either sulfate or chloride the net efflux of sulfate is low. However, chloride or sulfate on the trans side of the membrane is effective in accelerating unidirectional sulfate efflux. Taken together, the results of this investigation cannot be explained in terms of the membrane fixed charge hypothesis. Rather, they support the contention that sulfate transport across the tumor cell membrane is a carrier-mediated process."}
{"id": "PMID:234126", "title": "Influence of mono- and multivalent cations on the electrokinetic properties of Rana pipiens kidney cells.", "content": "Changes in the cation composition of the ambient cell environment, at constant ionic strengths, altered the electrokinetic properties of the surface of normal adult Rana pipiens kidney cells in a manner which reflected its valence. the effect was expressed in the changes of the magnitude of the net surface charge, at any pH, and in the shift of the isoelectric point of the cell surface.", "contents": "Influence of mono- and multivalent cations on the electrokinetic properties of Rana pipiens kidney cells. Changes in the cation composition of the ambient cell environment, at constant ionic strengths, altered the electrokinetic properties of the surface of normal adult Rana pipiens kidney cells in a manner which reflected its valence. the effect was expressed in the changes of the magnitude of the net surface charge, at any pH, and in the shift of the isoelectric point of the cell surface."}
{"id": "PMID:234127", "title": "Characterization of the ATP-phosphohydrolase activity of bovine spermatozoa flagellar extracts.", "content": "The ATP-phosphohydrolase activity of extracts prepared from bovine spermatozoa flagella (BSFE), was characterized with respect to enzyme, substrate, activator ion and salt concentration, temperature dependence and time stability. BSFE required the presence of a divalent cation for activity: Mg++ or Ca++ could function as activator; Mn++, Zn++ and Cd++ could not. EDTA, but not EGTA, was inhibitory to enzymatic activity. Ca++ inhibited the Mg++ stimulated activity. ATP was dephosphorylated more rapidly than GTP greater than CTP greater than ITP, and ADP was dephosphorylated at 40% of the rate of ATP. The magnesium activated ATPase was stimulated by potassium and inhibited by sodium ions. Activation of BSFE ATP-phosphohydrolase was maximal in the presence of Mg++ and ATP in equimolar concentrations and K+ (0.05-0.3 M) at 30 degrees C. Although the enzymatic activity of the extract was found to decrease rapidly with time, it could be maintained for up to three days by the addition of 2-beta-mercaptoethanol to the bovine spermatozoa flagellar extracts.", "contents": "Characterization of the ATP-phosphohydrolase activity of bovine spermatozoa flagellar extracts. The ATP-phosphohydrolase activity of extracts prepared from bovine spermatozoa flagella (BSFE), was characterized with respect to enzyme, substrate, activator ion and salt concentration, temperature dependence and time stability. BSFE required the presence of a divalent cation for activity: Mg++ or Ca++ could function as activator; Mn++, Zn++ and Cd++ could not. EDTA, but not EGTA, was inhibitory to enzymatic activity. Ca++ inhibited the Mg++ stimulated activity. ATP was dephosphorylated more rapidly than GTP greater than CTP greater than ITP, and ADP was dephosphorylated at 40% of the rate of ATP. The magnesium activated ATPase was stimulated by potassium and inhibited by sodium ions. Activation of BSFE ATP-phosphohydrolase was maximal in the presence of Mg++ and ATP in equimolar concentrations and K+ (0.05-0.3 M) at 30 degrees C. Although the enzymatic activity of the extract was found to decrease rapidly with time, it could be maintained for up to three days by the addition of 2-beta-mercaptoethanol to the bovine spermatozoa flagellar extracts."}
{"id": "PMID:234130", "title": "Influence of an experimental sodium fluoride dentifrice on dental caries incidence in children.", "content": "Schoolchildren residing in a fluoride-deficient area were provided either a sodium fluoride (0.1% F) or a nonfluoride dentifrice for home use. About half the children provided each type of dentifrice were also given an initial prophylaxis. Combining the data with regard to the type of dentifrice indicated that the sodium fluoride dentifrice resulted in dental caries reductions of 24 and 26% as noted by the two examiners, respectively.", "contents": "Influence of an experimental sodium fluoride dentifrice on dental caries incidence in children. Schoolchildren residing in a fluoride-deficient area were provided either a sodium fluoride (0.1% F) or a nonfluoride dentifrice for home use. About half the children provided each type of dentifrice were also given an initial prophylaxis. Combining the data with regard to the type of dentifrice indicated that the sodium fluoride dentifrice resulted in dental caries reductions of 24 and 26% as noted by the two examiners, respectively."}
{"id": "PMID:234129", "title": "Studies on Ca2+-stimulated adenosine triphosphatase in rat submandibular glands: its distribution and properties.", "content": "Intracellular distribution and some characteristics of a Ca2+-stimulated adenosine triphosphatase (ATPase) in rat submandibular glands were investigated. This enzyme was activated by calcium alone, and magnesium was not necessary for its activation. Mg2+-stimulated ATPase also was investigated in the same enzyme preparations.", "contents": "Studies on Ca2+-stimulated adenosine triphosphatase in rat submandibular glands: its distribution and properties. Intracellular distribution and some characteristics of a Ca2+-stimulated adenosine triphosphatase (ATPase) in rat submandibular glands were investigated. This enzyme was activated by calcium alone, and magnesium was not necessary for its activation. Mg2+-stimulated ATPase also was investigated in the same enzyme preparations."}
{"id": "PMID:234131", "title": "Formation of CaHPO4-2H2O in tooth enamel as an intermediate product in topical fluoride treatments.", "content": "Significant amounts of CaHPO4-2H2O (DCPD) were deposited in tooth enamel by pretreatment with a solution saturated with respect to DCPD. When these enamel samples were treated with a given fluoride solution, the fluoride uptake increased with increasing amounts of DCPD produced by the pretreatment. The interactions between enamel and acidic solutions to yield DCPD can be understood as dissolution-precipitation reactions and analyzed through the use of solubility phase diagrams.", "contents": "Formation of CaHPO4-2H2O in tooth enamel as an intermediate product in topical fluoride treatments. Significant amounts of CaHPO4-2H2O (DCPD) were deposited in tooth enamel by pretreatment with a solution saturated with respect to DCPD. When these enamel samples were treated with a given fluoride solution, the fluoride uptake increased with increasing amounts of DCPD produced by the pretreatment. The interactions between enamel and acidic solutions to yield DCPD can be understood as dissolution-precipitation reactions and analyzed through the use of solubility phase diagrams."}
{"id": "PMID:234132", "title": "Postdevelopmental effects of boron, fluoride, and their combination on dental caries activity in the rat.", "content": "Drinking water of rats aged 21 days was supplemented with 1, 10, 30, 50, 100, or 283 ppm of boron or 10 or 25 ppm of fluoride individually or in combination. All rats were fed a cariogenic diet. Boron did not reduce dental caries activity in erupted molars after eight weeks. When given in combination, it partially antagonized the cariostatic effect of fluoride.", "contents": "Postdevelopmental effects of boron, fluoride, and their combination on dental caries activity in the rat. Drinking water of rats aged 21 days was supplemented with 1, 10, 30, 50, 100, or 283 ppm of boron or 10 or 25 ppm of fluoride individually or in combination. All rats were fed a cariogenic diet. Boron did not reduce dental caries activity in erupted molars after eight weeks. When given in combination, it partially antagonized the cariostatic effect of fluoride."}
{"id": "PMID:234141", "title": "Phytate destruction by yeast fermentation in whole wheat meals. Study of high-extraction rate meals.", "content": "Destruction of phytate by yeast fermentation is compared in sponges prepared from Iranian whole wheat meals of different extraction rates. Phytate was destroyed rapidly in whole meals of 75 to 85 and 85 to 90 per cent extraction, but destruction was retarded in those of 95 to 100 per cent extraction. Production of acid-soluble phosphorus kept pace with phytate destruction in the two whole meals of lower extraction rates but was delayed with less-than-expected yield in those of 95 to 100 per cent rate. Unleavened whole meal bread contains little acid-soluble phosphorus. Leavened breads made from whole meals of slightly lower extraction rate average five times as much. Since phytate phosphorus appears to remain unavailable in the small intestine in many circumstances, dependece on unleavened whole meal bread may result in critically low intakes of available phosphorus when other sources are lacking in the diet. It is concluded that replacement of the whole meals of 95 to 100 per cent extraction rate, presently the main staple of the diet of rural Iran, by those of somewhat lower rate is an important preliminary to the introduction of leaven and fermentation into village bread-making methods.", "contents": "Phytate destruction by yeast fermentation in whole wheat meals. Study of high-extraction rate meals. Destruction of phytate by yeast fermentation is compared in sponges prepared from Iranian whole wheat meals of different extraction rates. Phytate was destroyed rapidly in whole meals of 75 to 85 and 85 to 90 per cent extraction, but destruction was retarded in those of 95 to 100 per cent extraction. Production of acid-soluble phosphorus kept pace with phytate destruction in the two whole meals of lower extraction rates but was delayed with less-than-expected yield in those of 95 to 100 per cent rate. Unleavened whole meal bread contains little acid-soluble phosphorus. Leavened breads made from whole meals of slightly lower extraction rate average five times as much. Since phytate phosphorus appears to remain unavailable in the small intestine in many circumstances, dependece on unleavened whole meal bread may result in critically low intakes of available phosphorus when other sources are lacking in the diet. It is concluded that replacement of the whole meals of 95 to 100 per cent extraction rate, presently the main staple of the diet of rural Iran, by those of somewhat lower rate is an important preliminary to the introduction of leaven and fermentation into village bread-making methods."}
{"id": "PMID:234143", "title": "Autoradiographic study of mouse spermatozoan arginine-rich nuclear protein in fertilization.", "content": "General labeling of ripe mouse spermatozoa was obtained two weeks after six injections of L-arginine-5-3H monohydrochloride, administered within two days. Besides tail labeling a very intensive nuclear labeling was obtained. It is presumed that this nuclear labeling represents almost exclusively tritiated arginine incorporation into basic nuclear protein. Mouse oocytes were fertilized in vitro with such labeled spermatozoa. It was found that the nuclear label is lost very early during male pronucleus formation, probably concomitantly with sperm chromatin decondensation. This might indicate total loss of the basic spermatozoal nuclear protein before male genome activation.", "contents": "Autoradiographic study of mouse spermatozoan arginine-rich nuclear protein in fertilization. General labeling of ripe mouse spermatozoa was obtained two weeks after six injections of L-arginine-5-3H monohydrochloride, administered within two days. Besides tail labeling a very intensive nuclear labeling was obtained. It is presumed that this nuclear labeling represents almost exclusively tritiated arginine incorporation into basic nuclear protein. Mouse oocytes were fertilized in vitro with such labeled spermatozoa. It was found that the nuclear label is lost very early during male pronucleus formation, probably concomitantly with sperm chromatin decondensation. This might indicate total loss of the basic spermatozoal nuclear protein before male genome activation."}
{"id": "PMID:234144", "title": "Micropuncture analysis of the cellular mechanisms of electrolyte secretion by the in vitro rabbit pancreas.", "content": "Micropuncture techniques have been used to study electrolyte secretion by the spontaneously secreting in vitro rabbit pancreas over a wide range of environmental conditions. Pancreatic secretion does not have a strong requirement for HCO3 and secretion continues at nearly normal rates when exogenous HCO3 is replaced by acetate. Acetate concentration in the juice averages 70 meq/liter, nearly three times the environmental concentration. The similar characteristics exhibited by HCO3 and acetate secretion indicate that they are secreted by a common mechanism involving active H transport. In vitro acid-base alterations demonstrate that the secretion rate is controlled by the environmental HCO3 concentration and to a much lesser extent by the pCO2. Secretion also requires active Na transport across the mucosal membrane. The effects of ouabain and a low Na environment strongly suggest coupling between the transport of Na and H and a cellular mechanism for electrolyte secretion is proposed involving Na-H exchange mechanisms at both the mucosal and serosal membranes.", "contents": "Micropuncture analysis of the cellular mechanisms of electrolyte secretion by the in vitro rabbit pancreas. Micropuncture techniques have been used to study electrolyte secretion by the spontaneously secreting in vitro rabbit pancreas over a wide range of environmental conditions. Pancreatic secretion does not have a strong requirement for HCO3 and secretion continues at nearly normal rates when exogenous HCO3 is replaced by acetate. Acetate concentration in the juice averages 70 meq/liter, nearly three times the environmental concentration. The similar characteristics exhibited by HCO3 and acetate secretion indicate that they are secreted by a common mechanism involving active H transport. In vitro acid-base alterations demonstrate that the secretion rate is controlled by the environmental HCO3 concentration and to a much lesser extent by the pCO2. Secretion also requires active Na transport across the mucosal membrane. The effects of ouabain and a low Na environment strongly suggest coupling between the transport of Na and H and a cellular mechanism for electrolyte secretion is proposed involving Na-H exchange mechanisms at both the mucosal and serosal membranes."}
{"id": "PMID:234145", "title": "Role of calcium in volume regulation by dog red blood cells.", "content": "Dog red blood cells (RBC) are shown to regulate their volume in anisosmotic media. Extrusion of water from osmotically swollen cells requires external calcium and is associated with net outward sodium movement. Accumulation of water by osmotically shrunken cells is not calcium dependent and is associated with net sodium uptake. Net movements of calcium are influenced by several variables including cell volume, pH, medium sodium concentration, and cellular sodium concentration. Osmotic swelling of cells increases calcium permeability, and this effect is diminished at acid pH. Net calcium flux in either direction between cells and medium is facilitated when the sodium concentrations is low in the compartment from which calcium moves and/or high in the compartment to which calcium moves. The hypothesis is advanced that energy for active sodium extrusion in dog RBC comes from passive, inward flow of calcium through a countertransport mechanism.", "contents": "Role of calcium in volume regulation by dog red blood cells. Dog red blood cells (RBC) are shown to regulate their volume in anisosmotic media. Extrusion of water from osmotically swollen cells requires external calcium and is associated with net outward sodium movement. Accumulation of water by osmotically shrunken cells is not calcium dependent and is associated with net sodium uptake. Net movements of calcium are influenced by several variables including cell volume, pH, medium sodium concentration, and cellular sodium concentration. Osmotic swelling of cells increases calcium permeability, and this effect is diminished at acid pH. Net calcium flux in either direction between cells and medium is facilitated when the sodium concentrations is low in the compartment from which calcium moves and/or high in the compartment to which calcium moves. The hypothesis is advanced that energy for active sodium extrusion in dog RBC comes from passive, inward flow of calcium through a countertransport mechanism."}
{"id": "PMID:234152", "title": "Improved growth media for Vibrio succinogenes.", "content": "Five new culture media for Vibrio succinogenes are described. Of these, a medium composed of 0.4% yeast extract, 100 mM ammonium formate, 120 mM sodium fumarate, and 0.05% sodium thioglycolate, pH 7.3, supports the best growth.", "contents": "Improved growth media for Vibrio succinogenes. Five new culture media for Vibrio succinogenes are described. Of these, a medium composed of 0.4% yeast extract, 100 mM ammonium formate, 120 mM sodium fumarate, and 0.05% sodium thioglycolate, pH 7.3, supports the best growth."}
{"id": "PMID:234153", "title": "Isolation of thermophilic fungi from snuff.", "content": "Fourteen samples of retail purchases of snuff were examined for the presence of viable thermophilic fungi; four species were found.", "contents": "Isolation of thermophilic fungi from snuff. Fourteen samples of retail purchases of snuff were examined for the presence of viable thermophilic fungi; four species were found."}
{"id": "PMID:234154", "title": "Development of a simple method for concentrating enteroviruses from oysters.", "content": "The development of a simple method for concentrating enteroviruses from oysters is described. In this method viruses in homogenized oyster tissues are efficiently absorbed to oyster solids at pH 5.5 and low salt concentration. After low-speed centrifugation, the supernatant is discarded and viruses are eluted from the sedimented oyster solids by resuspending them in pH 3.5 glycine-buffered saline. The solids are then removed by low-speed centrifugation, and the virus-containing supernatant is filtered through a 0.2-micronm porosity filter to remove bacteria and other small particulates without removing viruses. The virus-containing filtrate is then concentrated to a volume of a few milliliters by ultrafiltration, and the concentrate obtained is inoculated directly into cell cultures for virus assay. When tested with pools of oysters experimentally contaminated with small amounts of different enteroviruses, virus recovery efficiency averaged 63%.", "contents": "Development of a simple method for concentrating enteroviruses from oysters. The development of a simple method for concentrating enteroviruses from oysters is described. In this method viruses in homogenized oyster tissues are efficiently absorbed to oyster solids at pH 5.5 and low salt concentration. After low-speed centrifugation, the supernatant is discarded and viruses are eluted from the sedimented oyster solids by resuspending them in pH 3.5 glycine-buffered saline. The solids are then removed by low-speed centrifugation, and the virus-containing supernatant is filtered through a 0.2-micronm porosity filter to remove bacteria and other small particulates without removing viruses. The virus-containing filtrate is then concentrated to a volume of a few milliliters by ultrafiltration, and the concentrate obtained is inoculated directly into cell cultures for virus assay. When tested with pools of oysters experimentally contaminated with small amounts of different enteroviruses, virus recovery efficiency averaged 63%."}
{"id": "PMID:234155", "title": "Agar plate method for detection and enumeration of alkylbenzenesulfonate-degrading microorganisms.", "content": "A simple method for detection and enumeration of alkylbenzenesulfonate (ABS)-degrading microorganisms by using agar plates was developed and used in microbiological studies of coastal marine and polluted river waters. The method depends upon the color responses of neutral red in alkaline medium. Neutral red changes from pink, when it enters into ABS micelles, to yellow, when the ABS is degraded, and does not form micelles. When neutral red-tris(hydroxymethyl)-aminomethane buffer solution and then cationic surfactant solution were sprayed onto the agar surface of ABS-nutrient agar cultures, transparent haloes appeared around the colonies of ABS-degrading microorganisms against a pink background. Viable counts of ABS-degrading bacteria isolated from both seawater and freshwater environments were considerably higher in polluted waters than in less polluted areas. Viable counts of ABS-degrading bacteria averaged 1.5 x 105/ml in samples from the surface water of polluted Tokyo Bay and 3.0 x 104/ml in samples from the surface water of polluted Tamagawa River but were fewer in number in samples from less polluted waters.", "contents": "Agar plate method for detection and enumeration of alkylbenzenesulfonate-degrading microorganisms. A simple method for detection and enumeration of alkylbenzenesulfonate (ABS)-degrading microorganisms by using agar plates was developed and used in microbiological studies of coastal marine and polluted river waters. The method depends upon the color responses of neutral red in alkaline medium. Neutral red changes from pink, when it enters into ABS micelles, to yellow, when the ABS is degraded, and does not form micelles. When neutral red-tris(hydroxymethyl)-aminomethane buffer solution and then cationic surfactant solution were sprayed onto the agar surface of ABS-nutrient agar cultures, transparent haloes appeared around the colonies of ABS-degrading microorganisms against a pink background. Viable counts of ABS-degrading bacteria isolated from both seawater and freshwater environments were considerably higher in polluted waters than in less polluted areas. Viable counts of ABS-degrading bacteria averaged 1.5 x 105/ml in samples from the surface water of polluted Tokyo Bay and 3.0 x 104/ml in samples from the surface water of polluted Tamagawa River but were fewer in number in samples from less polluted waters."}
{"id": "PMID:234156", "title": "Biological modification of trichothecene mycotoxins: acetylation and deacetylation of deoxynivalenols by Fusarium spp.", "content": "Attempts were made to elucidate the acetyl transformation of novel trichothecene mycotoxins, 3a,7a,15-trihydroxy-12,13-epoxytrichothec-9-en-8-one (deoxynivalenol) and its derivatives, by trichothecene-producing strains of Fusarium nivale, F. roseum, and F. solani. In the peptone-supplemented Czapek-Dox medium, F. roseum converted 3a-acetoxy-7a,15-dihydroxy-12,13-epoxytrichothec-9-en-8-one (3-acetyldeoxynivalenol) to deoxynivalenol. 3-Acetyldeoxynivalenol was also deacetylated by intact mycelia of the three strains in sugar-free Czapek-Dox medium. The growing F. nivale acetylated deoxynivalenol to afford a small amount of 3-acetyldeoxynivalenol. 3a,7a,15-Triacetoxy-12,13-epoxytrichothec-9-en-8-one (7,15-diacetyl-deoxynivalenol), which was then deacetylated to give 7a-acetoxy-3a,15-dihydroxy-12,13-epoxytrichothec-9-en-8-one (7-acetyldeoxynivalenol). It was noted that the ester at C-7 was not hydrolyzed by the fungal mycelium.", "contents": "Biological modification of trichothecene mycotoxins: acetylation and deacetylation of deoxynivalenols by Fusarium spp. Attempts were made to elucidate the acetyl transformation of novel trichothecene mycotoxins, 3a,7a,15-trihydroxy-12,13-epoxytrichothec-9-en-8-one (deoxynivalenol) and its derivatives, by trichothecene-producing strains of Fusarium nivale, F. roseum, and F. solani. In the peptone-supplemented Czapek-Dox medium, F. roseum converted 3a-acetoxy-7a,15-dihydroxy-12,13-epoxytrichothec-9-en-8-one (3-acetyldeoxynivalenol) to deoxynivalenol. 3-Acetyldeoxynivalenol was also deacetylated by intact mycelia of the three strains in sugar-free Czapek-Dox medium. The growing F. nivale acetylated deoxynivalenol to afford a small amount of 3-acetyldeoxynivalenol. 3a,7a,15-Triacetoxy-12,13-epoxytrichothec-9-en-8-one (7,15-diacetyl-deoxynivalenol), which was then deacetylated to give 7a-acetoxy-3a,15-dihydroxy-12,13-epoxytrichothec-9-en-8-one (7-acetyldeoxynivalenol). It was noted that the ester at C-7 was not hydrolyzed by the fungal mycelium."}
{"id": "PMID:234157", "title": "Simple process for the reduction in the nucleic acid content in yeast.", "content": "A simple one-step process for the nucleic acid reduction in Rhodotorula glutinis is described. The process consists of submitting the yeast cells to a heat treatment in an acidic (pH 2) spent medium. The optimal temperature for pH 2 medium is 90 C and the final nucleic acid content in treated yeasts was 1.2%. Heat treatment at acidic pH is preferred to that at alkaline pH because it offers a better protection for amino acids and crude protein, while being more efficient in lowering the nucleic acid level. The new process is economic and rapid and could be easily used for industrial application.", "contents": "Simple process for the reduction in the nucleic acid content in yeast. A simple one-step process for the nucleic acid reduction in Rhodotorula glutinis is described. The process consists of submitting the yeast cells to a heat treatment in an acidic (pH 2) spent medium. The optimal temperature for pH 2 medium is 90 C and the final nucleic acid content in treated yeasts was 1.2%. Heat treatment at acidic pH is preferred to that at alkaline pH because it offers a better protection for amino acids and crude protein, while being more efficient in lowering the nucleic acid level. The new process is economic and rapid and could be easily used for industrial application."}
{"id": "PMID:234158", "title": "Effect of pH and sodium chloride on growth of Bacillus cereus in laboratory media and certain foods.", "content": "The effects of NaCl concentration, pH, and water activity (aw) on the ability of vegetative cells of Bacillus cereus to initiate aerobic growth in brain heart infusion broth at 30 C were studied in a factorial design experiment. By using multiple regression techniques, equations were derived which related the decimal reduction of the bacterial population to the concentration of NaCl and pH of broth to which the population was exposed. From these equations, the percentage of inoculated cells capable of initiating growth could be calculated. The reliability of these equations in foods was tested in laboratory-processed meat and rice media. The foods were less inhibitory than the broths, so that accurate prediction of growth initiation in foods was not possible by using the developed formulas. The impact of this type of quantitative study on the development of specific microbial standards for foods is discussed. When the NaCl concentration is increased, the aw is decreased and, with increased deviation of pH from optimum, more concentrated inoculum of B. cereus cells is needed to assure initiation of growth in culture media and foods.", "contents": "Effect of pH and sodium chloride on growth of Bacillus cereus in laboratory media and certain foods. The effects of NaCl concentration, pH, and water activity (aw) on the ability of vegetative cells of Bacillus cereus to initiate aerobic growth in brain heart infusion broth at 30 C were studied in a factorial design experiment. By using multiple regression techniques, equations were derived which related the decimal reduction of the bacterial population to the concentration of NaCl and pH of broth to which the population was exposed. From these equations, the percentage of inoculated cells capable of initiating growth could be calculated. The reliability of these equations in foods was tested in laboratory-processed meat and rice media. The foods were less inhibitory than the broths, so that accurate prediction of growth initiation in foods was not possible by using the developed formulas. The impact of this type of quantitative study on the development of specific microbial standards for foods is discussed. When the NaCl concentration is increased, the aw is decreased and, with increased deviation of pH from optimum, more concentrated inoculum of B. cereus cells is needed to assure initiation of growth in culture media and foods."}
{"id": "PMID:234159", "title": "Beta-galactosidase of Propionibacterium shermanii.", "content": "Ten strains of Propionibacterium shermanii were tested for beta-galactosidase (beta-gal) activity. Of these ten strains, five yielded enhanced enzyme activity when cell suspensions were treated with toluene-acetone; on solvent treatment, the remaining five lost a considerable portion of the activity found in whole-cell suspensions. By using a strain yielding decreased activity upon solvent treatment, explanations for the loss in activity were sought through assays for possible alternative beta-galactoside utilization mechanisms. When this strain was assayed for beta-D-phosphogalactoside galactohydrolase by using orthonitrophenyl-beta-D-galactopyranoside-6-P04 as a substrate, the activity was wither lower or indiffernt as compared with beta-gal activity determined simultaneously. Cell suspensions of P. shermanii 7 and 22 (strains chosen for further work) grown separately on the individual substrates (lactose, glucose, galactose, and sodium lactate) did not show significant differences in beta-gal activity. Optimal temperature for beta-gal activity in untreated and toluene-acetone-treated cell suspensions of strain 7 was 52 C. With strain 22, of the temperatures tested, maximal activity in untreated cell suspensions was noted at 58 C and with solvent-treated cells at 32 C. In the cell-free extract (CFE) system, both strains exhibited maximal activity at 52 C. Optimal pH for untreated and solvent-treated cell suspensions of both strains was around 7.5. In the P. shermanii 22 CFE system, maximal activity occurred at pH 7.0; pH had very little effect on enzyme activity in P. shermanii 7 CFE. Sodium or potassium phosphate buffers in the assay system yielded the best activity. In the CFE system of these two strains, Mn2+ was definitely stimulatory, but in untreated and solvent-treated cell systems of these strains presence or absence of Mn2+ in the assay system had variable effects on enzyme activity. Maximal beta-gal activity was noted in P. shermanii 7 cells harvested after 28 h of growth at 32 C in sodium lactate broth. Sulfhydryl-group blocking agents inhibited enzyme activity in P. shermanii 22 CFE; the inhibition was partly reversed by dithiothreitol.", "contents": "Beta-galactosidase of Propionibacterium shermanii. Ten strains of Propionibacterium shermanii were tested for beta-galactosidase (beta-gal) activity. Of these ten strains, five yielded enhanced enzyme activity when cell suspensions were treated with toluene-acetone; on solvent treatment, the remaining five lost a considerable portion of the activity found in whole-cell suspensions. By using a strain yielding decreased activity upon solvent treatment, explanations for the loss in activity were sought through assays for possible alternative beta-galactoside utilization mechanisms. When this strain was assayed for beta-D-phosphogalactoside galactohydrolase by using orthonitrophenyl-beta-D-galactopyranoside-6-P04 as a substrate, the activity was wither lower or indiffernt as compared with beta-gal activity determined simultaneously. Cell suspensions of P. shermanii 7 and 22 (strains chosen for further work) grown separately on the individual substrates (lactose, glucose, galactose, and sodium lactate) did not show significant differences in beta-gal activity. Optimal temperature for beta-gal activity in untreated and toluene-acetone-treated cell suspensions of strain 7 was 52 C. With strain 22, of the temperatures tested, maximal activity in untreated cell suspensions was noted at 58 C and with solvent-treated cells at 32 C. In the cell-free extract (CFE) system, both strains exhibited maximal activity at 52 C. Optimal pH for untreated and solvent-treated cell suspensions of both strains was around 7.5. In the P. shermanii 22 CFE system, maximal activity occurred at pH 7.0; pH had very little effect on enzyme activity in P. shermanii 7 CFE. Sodium or potassium phosphate buffers in the assay system yielded the best activity. In the CFE system of these two strains, Mn2+ was definitely stimulatory, but in untreated and solvent-treated cell systems of these strains presence or absence of Mn2+ in the assay system had variable effects on enzyme activity. Maximal beta-gal activity was noted in P. shermanii 7 cells harvested after 28 h of growth at 32 C in sodium lactate broth. Sulfhydryl-group blocking agents inhibited enzyme activity in P. shermanii 22 CFE; the inhibition was partly reversed by dithiothreitol."}
{"id": "PMID:234160", "title": "Plaque production by arboviruses in Singh's Aedes albopictus cells.", "content": "We report plaquing tests of 124 virus strains, mostly arboviruses of 21 serological groups, in Singh's line of Aedes albopictus cells. Thirty of these plaqued: all were arboviruses of six groups and were known or presumed to be mosquito borne. Failing to plaque were 86 strains of arboviruses, mostly tick borne, two strains of insect pathogens, and six animal viruses not classified as arboviruses. Among mosquito-borne agents, plaquing ability appeared related to serological classification. California group and most A-group viruses failed to plaque, but nearly all members of B and Bunyamwera groups readily plaqued. Within serological group B, 14 of 16 mosquito-borne agents plaqued, but none of 13 tick-borne or vector-unassociated viruses did so. Some implications of these results for recognition and classification of arboviruses are discussed.", "contents": "Plaque production by arboviruses in Singh's Aedes albopictus cells. We report plaquing tests of 124 virus strains, mostly arboviruses of 21 serological groups, in Singh's line of Aedes albopictus cells. Thirty of these plaqued: all were arboviruses of six groups and were known or presumed to be mosquito borne. Failing to plaque were 86 strains of arboviruses, mostly tick borne, two strains of insect pathogens, and six animal viruses not classified as arboviruses. Among mosquito-borne agents, plaquing ability appeared related to serological classification. California group and most A-group viruses failed to plaque, but nearly all members of B and Bunyamwera groups readily plaqued. Within serological group B, 14 of 16 mosquito-borne agents plaqued, but none of 13 tick-borne or vector-unassociated viruses did so. Some implications of these results for recognition and classification of arboviruses are discussed."}
{"id": "PMID:234169", "title": "Renal conservation of ketone bodies during starvation.", "content": "Renal handling of acetoacetate and beta-hydroxybutyrate was studied in 12 obese subjects undergoing total starvation. Simultaneously, the acetoacetate, beta-hydroxybutyrate, and inulin clearance rates were measured, and acetoacetate and beta-hydroxybutyrate reabsorption rates were calculated. Renal clearance of blood acetoacetate and beta-hydroxybutyrate remained constant. In contrast, acetoacetate reabsorption rate increased significantly from 47 plus or minus 10 mumoles/min on day 3 to 106 plus or minus 15, 89 plus or minus 10, and 96 plus or minus 10 mumoles/min on days 10, 17, and 24, respectively. Similarly, beta-hydroxybutyrate reabsorption rate increased significantly from 154 plus or minus 27 mumoles/min on day 3 to 419 plus or minus 53, 399 plus or minus 25, and 436 plus or minus 53 mumoles/min on days 10, 17, and 24, respectively. Both acetoacetate and beta-hydroxybutyrate reabsorption rates increased linearly when plotted against their filtered loads. Thus, no tubular maximal transport rate exists for acetoacetate or beta-hydroxybutyrate during physiologic ketonemia. Conservation 450-500 mmoles of ketone bodies/day prevents large urinary losses of cations during prolonged starvation. Since ammonium becomes the major cation excreted during prolonged fasting, the increased renal reabsorption of ketone bodies minimizes body protein loss and aids in maintaining high circulating acetoacetate and beta-hydroxybutyrate concentrations.", "contents": "Renal conservation of ketone bodies during starvation. Renal handling of acetoacetate and beta-hydroxybutyrate was studied in 12 obese subjects undergoing total starvation. Simultaneously, the acetoacetate, beta-hydroxybutyrate, and inulin clearance rates were measured, and acetoacetate and beta-hydroxybutyrate reabsorption rates were calculated. Renal clearance of blood acetoacetate and beta-hydroxybutyrate remained constant. In contrast, acetoacetate reabsorption rate increased significantly from 47 plus or minus 10 mumoles/min on day 3 to 106 plus or minus 15, 89 plus or minus 10, and 96 plus or minus 10 mumoles/min on days 10, 17, and 24, respectively. Similarly, beta-hydroxybutyrate reabsorption rate increased significantly from 154 plus or minus 27 mumoles/min on day 3 to 419 plus or minus 53, 399 plus or minus 25, and 436 plus or minus 53 mumoles/min on days 10, 17, and 24, respectively. Both acetoacetate and beta-hydroxybutyrate reabsorption rates increased linearly when plotted against their filtered loads. Thus, no tubular maximal transport rate exists for acetoacetate or beta-hydroxybutyrate during physiologic ketonemia. Conservation 450-500 mmoles of ketone bodies/day prevents large urinary losses of cations during prolonged starvation. Since ammonium becomes the major cation excreted during prolonged fasting, the increased renal reabsorption of ketone bodies minimizes body protein loss and aids in maintaining high circulating acetoacetate and beta-hydroxybutyrate concentrations."}
{"id": "PMID:234174", "title": "Optimum end-expiratory airway pressure in patients with acute pulmonary failure.", "content": "To determine whether in the management of pulmonary failure, the maximum compliance produced by positive end-expiratory pressure coincides with optimum lung function, 15 normovolemic patients requiring mechanical ventilation for acute pulmonary failure were studied. The end-expiratory pressure resulting in maximum oxygen transport (cardiac output times arterial oxygen content) and the lowest dead-space fraction both resulted in the greatest total static compliance. This end-expiratory pressure varied between 0 and 15 cm of water and correlated inversely with functional residual capacity at zero end-expiratory pressure (r equal -0.72, p less than or equal to 0.005). Mixed venous oxygen tension increased between zero end-expiratory pressure and the end-expiratory pressure resulting in maximum oxygen transport, but then decreased at higher end-expiratory pressures. When measurements of cardiac output or of true mixed venous blood are not available, compliance may be used to indicate the end-expiratory pressure likely to result in optimum cardiopulmonary function.", "contents": "Optimum end-expiratory airway pressure in patients with acute pulmonary failure. To determine whether in the management of pulmonary failure, the maximum compliance produced by positive end-expiratory pressure coincides with optimum lung function, 15 normovolemic patients requiring mechanical ventilation for acute pulmonary failure were studied. The end-expiratory pressure resulting in maximum oxygen transport (cardiac output times arterial oxygen content) and the lowest dead-space fraction both resulted in the greatest total static compliance. This end-expiratory pressure varied between 0 and 15 cm of water and correlated inversely with functional residual capacity at zero end-expiratory pressure (r equal -0.72, p less than or equal to 0.005). Mixed venous oxygen tension increased between zero end-expiratory pressure and the end-expiratory pressure resulting in maximum oxygen transport, but then decreased at higher end-expiratory pressures. When measurements of cardiac output or of true mixed venous blood are not available, compliance may be used to indicate the end-expiratory pressure likely to result in optimum cardiopulmonary function."}
{"id": "PMID:234181", "title": "Uptake and efflux of 14-C-dopamine in platelets: evidence for a generalized defect in Parkinson's disease.", "content": "Thirty-five parkinsonian patients (five untreated, six with levodopa only, seven with levodopa plus Ro 4-4602, nine with anticholinergic and/or antihistaminic medication, and eight with the anticholinergic/antihistaminic medication plus amantadine) and 35 age-matched control subjects were studied. Platelets isolated from each individual plasma were incubated with 14C-dopamine. Uptake was found to be decreased to a significant degree in all treated or untreated parkinsonian patients when compared with control subjects. Anticholinergic and/or antihistaminic medication, with or without amantadine, further decreased the dopamine uptake into platelets, while levodopa alone or with Ro 4-4602 returned uptake values to near normal. Dopamine efflux paralleled exactly the uptake values. The fact that parkinsonian platelets exhibit impaired dopamine uptake, while age-matched control platelets do not, constitutes the first direct evidence in favor of a generalized dopamine defect in Parkinson's disease.", "contents": "Uptake and efflux of 14-C-dopamine in platelets: evidence for a generalized defect in Parkinson's disease. Thirty-five parkinsonian patients (five untreated, six with levodopa only, seven with levodopa plus Ro 4-4602, nine with anticholinergic and/or antihistaminic medication, and eight with the anticholinergic/antihistaminic medication plus amantadine) and 35 age-matched control subjects were studied. Platelets isolated from each individual plasma were incubated with 14C-dopamine. Uptake was found to be decreased to a significant degree in all treated or untreated parkinsonian patients when compared with control subjects. Anticholinergic and/or antihistaminic medication, with or without amantadine, further decreased the dopamine uptake into platelets, while levodopa alone or with Ro 4-4602 returned uptake values to near normal. Dopamine efflux paralleled exactly the uptake values. The fact that parkinsonian platelets exhibit impaired dopamine uptake, while age-matched control platelets do not, constitutes the first direct evidence in favor of a generalized dopamine defect in Parkinson's disease."}
{"id": "PMID:234182", "title": "The syndrome of systemic carnitine deficiency. Clinical, morphologic, biochemical, and pathophysiologic features.", "content": "An 11-year old boy had had recurrent episodes of hepatic and cerebral dysfunction and underdeveloped musculature. Overt weakness developed at age 10. Lipid excess, especially in type I fibers, was found in muscle. Hypertrophied smooth endoplasmic reticulum and excessive microbodies were present in liver. Marked carnitine deficiency was shown in skeletal muscle, plasma, and liver. Ketogenesis was impaired on a high fat diet, but omega oxidation of fatty acids was enhanced. There was excessive glucose uptake and essentially no oxidation of labeled long-chain fatty acids by perfused forearm muscles in vivo. Oral replacement therapy restored plasma carnitine levels to normal, but not liver or muscle carnitine levels, and was accompanied by clinical improvement.", "contents": "The syndrome of systemic carnitine deficiency. Clinical, morphologic, biochemical, and pathophysiologic features. An 11-year old boy had had recurrent episodes of hepatic and cerebral dysfunction and underdeveloped musculature. Overt weakness developed at age 10. Lipid excess, especially in type I fibers, was found in muscle. Hypertrophied smooth endoplasmic reticulum and excessive microbodies were present in liver. Marked carnitine deficiency was shown in skeletal muscle, plasma, and liver. Ketogenesis was impaired on a high fat diet, but omega oxidation of fatty acids was enhanced. There was excessive glucose uptake and essentially no oxidation of labeled long-chain fatty acids by perfused forearm muscles in vivo. Oral replacement therapy restored plasma carnitine levels to normal, but not liver or muscle carnitine levels, and was accompanied by clinical improvement."}
{"id": "PMID:234187", "title": "Chronic pulmonary insufficiency of prematurity (CPIP).", "content": "This report describes a syndrome of delayed respiratory distress occurring in premature infants usually under 1,250 gm at birth. Unlike hyaline membrane disease, this syndrome occurs after four to seven days in a previously healthy infant; also unlike hyaline membrane disease, it persists for two to four weeks. Chronic pulmonary insufficiency of prematurity (CPIP) carries a 10% to 20% mortality rate. The infants are frequently apneic, require supplemental oxygen, but lack the radiologic findings of hyaline membrane disease or bronchopulmonary dysplasia. When compared with nondistressed infants of similar birthweight, infants with CPIP demonstrate slowly progressive atelectasis, hypoxemia, and hypercapnia. Recovery is usually complete by 60 days of age. The importance of CPIP is that an awareness of its existence can eliminate a false sense of security, often communicated to anxious parents, during the four-to-seven-day grace period before its appearance is clinically obvious. The physiologic similarities between CPIP and hyaline membrane disease suggest that lack of surfactant may play a role in the pathogenesis of CPIP.", "contents": "Chronic pulmonary insufficiency of prematurity (CPIP). This report describes a syndrome of delayed respiratory distress occurring in premature infants usually under 1,250 gm at birth. Unlike hyaline membrane disease, this syndrome occurs after four to seven days in a previously healthy infant; also unlike hyaline membrane disease, it persists for two to four weeks. Chronic pulmonary insufficiency of prematurity (CPIP) carries a 10% to 20% mortality rate. The infants are frequently apneic, require supplemental oxygen, but lack the radiologic findings of hyaline membrane disease or bronchopulmonary dysplasia. When compared with nondistressed infants of similar birthweight, infants with CPIP demonstrate slowly progressive atelectasis, hypoxemia, and hypercapnia. Recovery is usually complete by 60 days of age. The importance of CPIP is that an awareness of its existence can eliminate a false sense of security, often communicated to anxious parents, during the four-to-seven-day grace period before its appearance is clinically obvious. The physiologic similarities between CPIP and hyaline membrane disease suggest that lack of surfactant may play a role in the pathogenesis of CPIP."}
{"id": "PMID:234188", "title": "Studies on cor pulmonale in cystic fibrosis: I. Effects of diuresis.", "content": "The effects of acute diuresis in patients with cor pulmonale secondary to cystic fibrosis were studied. Both hemodynamic parameters and arterial blood gas changes were investigated. The major effect noted was a significant reduction of systemic venous pressure. Pulmonary artery and pulmonary artery wedge pressure either remained constant or declined slightly. No consistent changes were noted in cardiac output or arterial blood gases. Acute diuresis of moderate degree appears to be a safe and effective manner in which to treat the systemic venous congestion of cor pulmonale in this situation.", "contents": "Studies on cor pulmonale in cystic fibrosis: I. Effects of diuresis. The effects of acute diuresis in patients with cor pulmonale secondary to cystic fibrosis were studied. Both hemodynamic parameters and arterial blood gas changes were investigated. The major effect noted was a significant reduction of systemic venous pressure. Pulmonary artery and pulmonary artery wedge pressure either remained constant or declined slightly. No consistent changes were noted in cardiac output or arterial blood gases. Acute diuresis of moderate degree appears to be a safe and effective manner in which to treat the systemic venous congestion of cor pulmonale in this situation."}
{"id": "PMID:234191", "title": "The phospholipase activity of sheep pancreatic juice.", "content": "Sheep pancreatic juice was found to contain at least two enzymes which hydrolysed biliary lecithin. One enzyme was heat and acid labile and hydrolysed the fatty acid from position 1 (phospholipase A1); the other was heat and acid stable hydrolysing the fatty acid at position 2 (phospholipase A2). Lysophospholipase activity was also present. The phospholipases were active at pH values greater than 4.2, and would therefore function in the acid conditions (pH 3-6) of the sheep small intestine. The activity of the pancreatic phospholipases, and A2 in particular, was dramatically stimulated by the presence of the secretions of Brunner's glands which could be important in accelerating the hydrolysis of biliary lecithin in the lumen of the intestine. Phospholipase A1 was sensitive to acid in the range pH 2.5-3.5 and could therefore be partially inactivated by abomasal digesta; but phospholipase A2 was resistent to acid treatment.", "contents": "The phospholipase activity of sheep pancreatic juice. Sheep pancreatic juice was found to contain at least two enzymes which hydrolysed biliary lecithin. One enzyme was heat and acid labile and hydrolysed the fatty acid from position 1 (phospholipase A1); the other was heat and acid stable hydrolysing the fatty acid at position 2 (phospholipase A2). Lysophospholipase activity was also present. The phospholipases were active at pH values greater than 4.2, and would therefore function in the acid conditions (pH 3-6) of the sheep small intestine. The activity of the pancreatic phospholipases, and A2 in particular, was dramatically stimulated by the presence of the secretions of Brunner's glands which could be important in accelerating the hydrolysis of biliary lecithin in the lumen of the intestine. Phospholipase A1 was sensitive to acid in the range pH 2.5-3.5 and could therefore be partially inactivated by abomasal digesta; but phospholipase A2 was resistent to acid treatment."}
{"id": "PMID:234195", "title": "The value of total aortography in the diagnosis of Takayasu's arteritis.", "content": "The arteriographic and clinical spectrum of Takayasu's arteritis in a series of 23 cases is reviewed. The incidence of the disease appears to be much higher than is generally suspected. Although it primarily afflicts young women, children are frequently affected. Two clinical stages of the disease are recognized: an early systemic and a late occlusive phase. The signs and symptoms of both stages are protean and variable. The pathological appearance varies with the activity and duration of the disease. Total aortography is of primary diagnostic importance in demonstrating the characteristic appearance of the diseased aorta.", "contents": "The value of total aortography in the diagnosis of Takayasu's arteritis. The arteriographic and clinical spectrum of Takayasu's arteritis in a series of 23 cases is reviewed. The incidence of the disease appears to be much higher than is generally suspected. Although it primarily afflicts young women, children are frequently affected. Two clinical stages of the disease are recognized: an early systemic and a late occlusive phase. The signs and symptoms of both stages are protean and variable. The pathological appearance varies with the activity and duration of the disease. Total aortography is of primary diagnostic importance in demonstrating the characteristic appearance of the diseased aorta."}
{"id": "PMID:234199", "title": "Plasma testosterone and dihydrotestosterone in male rats during sexual maturation and following orchidectomy and experimental bilateral cryptorchidism.", "content": "Plasma concentration of testosterone and dihydrotestosterone (17beta-hydroxy-5alpha-androstan-3-one) were measured at frequent intervals (daily between day 20 and 40) in intact male rats from early pre-pubertal stage to full maturity. Effect of orchidectomy and experimental bilateral cryptorchidism on these two blood-born compounds at different stages of sexual maturation was also studied. A distinct spurt in testosterone level was noted on day 26, and in 3 days a leval of 2600pg/ml was reached, which was about 90% of the highest peak value (2940 pg/ml) seen at day 70. In the same animals dihydrotestosterone spurt was noted at the same time, but the peak value (163 pg/ml) was reached later (day 33). Within 4 days after orchidectomy plasma testosterone level showed no significant change in 20-day old animals, but dropped to 15% of the intact value in 40-day old ones, while remaining at a steady level of about 23% in older animals. Plasma dihydrotestosterone was undetectable after orchidectomy at each stage of sexual maturation. With bilateral cryptorchid animals plasma testosterone was higher than seen in the intact 20-day old control, but remained similar at other stages of sexual maturation. Plasma dihydrotesterone in the same animals was significantly less (p less 0.01) than those seen in the intact controls at all stages of sexual development except in 20-day old ones, where it was essentially similar.", "contents": "Plasma testosterone and dihydrotestosterone in male rats during sexual maturation and following orchidectomy and experimental bilateral cryptorchidism. Plasma concentration of testosterone and dihydrotestosterone (17beta-hydroxy-5alpha-androstan-3-one) were measured at frequent intervals (daily between day 20 and 40) in intact male rats from early pre-pubertal stage to full maturity. Effect of orchidectomy and experimental bilateral cryptorchidism on these two blood-born compounds at different stages of sexual maturation was also studied. A distinct spurt in testosterone level was noted on day 26, and in 3 days a leval of 2600pg/ml was reached, which was about 90% of the highest peak value (2940 pg/ml) seen at day 70. In the same animals dihydrotestosterone spurt was noted at the same time, but the peak value (163 pg/ml) was reached later (day 33). Within 4 days after orchidectomy plasma testosterone level showed no significant change in 20-day old animals, but dropped to 15% of the intact value in 40-day old ones, while remaining at a steady level of about 23% in older animals. Plasma dihydrotestosterone was undetectable after orchidectomy at each stage of sexual maturation. With bilateral cryptorchid animals plasma testosterone was higher than seen in the intact 20-day old control, but remained similar at other stages of sexual maturation. Plasma dihydrotesterone in the same animals was significantly less (p less 0.01) than those seen in the intact controls at all stages of sexual development except in 20-day old ones, where it was essentially similar."}
{"id": "PMID:234201", "title": "Solubility fo fibrin clots in monochloroacetic acid. A reflection of serum pepsinogen levels.", "content": "Fibrin clots formed from normal plasma dissolve readily in 1% monochloroacetic acid at 37 C. However, if the clots are washed thoroughly before the acid is added, they are no longer soluble. The agent present in the serum which causes dissolution of the fibrin clot was isolated and identified as pepsinogen. Because of the low pH of monochloroacetic acid the pepsinogen is activated and the clots are digested, simulating the dispersion of a fibrin clot which occurs in the absence of fibrin-stabilizing factor (factor XIII). Because of its higher pH, urea will not activate pepsinogen and is therefore a better agent to screen factor XIII deficiencies.", "contents": "Solubility fo fibrin clots in monochloroacetic acid. A reflection of serum pepsinogen levels. Fibrin clots formed from normal plasma dissolve readily in 1% monochloroacetic acid at 37 C. However, if the clots are washed thoroughly before the acid is added, they are no longer soluble. The agent present in the serum which causes dissolution of the fibrin clot was isolated and identified as pepsinogen. Because of the low pH of monochloroacetic acid the pepsinogen is activated and the clots are digested, simulating the dispersion of a fibrin clot which occurs in the absence of fibrin-stabilizing factor (factor XIII). Because of its higher pH, urea will not activate pepsinogen and is therefore a better agent to screen factor XIII deficiencies."}
{"id": "PMID:234203", "title": "Perceived life-stress and psychopathology among mothers of young children.", "content": "Mentally ill mothers of young children, contrasted with well mothers, reported greater stress in their own lives, and in those of their husbands and parental families. Within each group of mothers, there was a different relationship between life-stress and psychological symptoms. Within the mentally ill group, stress was associated with both diagnosis and chronicity.", "contents": "Perceived life-stress and psychopathology among mothers of young children. Mentally ill mothers of young children, contrasted with well mothers, reported greater stress in their own lives, and in those of their husbands and parental families. Within each group of mothers, there was a different relationship between life-stress and psychological symptoms. Within the mentally ill group, stress was associated with both diagnosis and chronicity."}
{"id": "PMID:234204", "title": "Elevated blood serotonin concentrations in unmediated chronic schizophrenic patients: a preliminary study.", "content": "The authors found higher serotonin concentrations in the blood of unmedicated chronic schizophrenic patients than in the blood of medicated schizophrenic patients or normal control subjects. This finding is consistent with the previous observation that the level of monoamine oxidase activity is low in the platelets of chronic schizophrenics.", "contents": "Elevated blood serotonin concentrations in unmediated chronic schizophrenic patients: a preliminary study. The authors found higher serotonin concentrations in the blood of unmedicated chronic schizophrenic patients than in the blood of medicated schizophrenic patients or normal control subjects. This finding is consistent with the previous observation that the level of monoamine oxidase activity is low in the platelets of chronic schizophrenics."}
{"id": "PMID:234205", "title": "Ecology of California encephalitis viruses on the Del Mar Va Peninsula. I. Virus isolations from mosquitoes.", "content": "The ecology of California encephalitis viruses was studied on the Del Mar Va Peninsula. Adult mosquitoes were collected weekly from May to October of 1971 and monthly from May to October of 1972, using CDC miniature light traps with Dry Ice. Floodwater mosquitoes were assayed for virus in suckling mice or cell cultures. In 1971 over 77,000 mosquitoes were processed, resulting in 33 virus isolations. In 1972, over 106,000 were processed and 63 virus strains were recovered. Of the 1971 strains, all but one were recovered from Aedes atlanticus mosquitoes, and of the 1972 strains all but two were recovered from A. atlanticus. All A. atlanticus strains were neutralized by Keystone virus mouse hyperimmune ascitic fluid (MHAF). All other strains were recovered from A. canadensis mosquitoes. The single 1971 strain, and one strain from 1972, were neutralized by Jamestown Canyon MHAF. The remaining strain was neutralized by Keystone MHAF. The rate of virus recovery from A. atlanticus remained approximately the same, both between years and during each year studied, even during periods when large numbers of adults were emerging, suggesting that these mosquitoes had emerged infected.", "contents": "Ecology of California encephalitis viruses on the Del Mar Va Peninsula. I. Virus isolations from mosquitoes. The ecology of California encephalitis viruses was studied on the Del Mar Va Peninsula. Adult mosquitoes were collected weekly from May to October of 1971 and monthly from May to October of 1972, using CDC miniature light traps with Dry Ice. Floodwater mosquitoes were assayed for virus in suckling mice or cell cultures. In 1971 over 77,000 mosquitoes were processed, resulting in 33 virus isolations. In 1972, over 106,000 were processed and 63 virus strains were recovered. Of the 1971 strains, all but one were recovered from Aedes atlanticus mosquitoes, and of the 1972 strains all but two were recovered from A. atlanticus. All A. atlanticus strains were neutralized by Keystone virus mouse hyperimmune ascitic fluid (MHAF). All other strains were recovered from A. canadensis mosquitoes. The single 1971 strain, and one strain from 1972, were neutralized by Jamestown Canyon MHAF. The remaining strain was neutralized by Keystone MHAF. The rate of virus recovery from A. atlanticus remained approximately the same, both between years and during each year studied, even during periods when large numbers of adults were emerging, suggesting that these mosquitoes had emerged infected."}
{"id": "PMID:234206", "title": "Bertioga (Guama group) and Anhembi (Bunyamwera group), two new arboviruses isolated in S\u00e3o Paulo, Brazil.", "content": "Bertioga and Anhembi are two newly recognized arboviruses that were isolated in Sa\u00f5 Paulo, Brazil. Bertioga was isolated from sentinel mice exposed in a forest of that name, and was shown to belong serologically to the Guama group of arboviruses. Anhembi, the second virus described, was isolated from pools of mosquitoes (Phoniomyia pilicauda and trichoprosopon pallidiventer), and from a spiny rat (Proechimys iheringi), and was shown to be a new member of the Bunyamwera group. The viruses are sensitive to sodium desoxycholate and are filterable through a millipore membrane of 450 mum pore size. Both are pathogenic for suckling mice and grow well in Vero cells, producing clear cytopathic effects. Detailed antigenic comparisons of Anhembi virus with other members of the Bunyamwera group isolated in the Americas, and of Bertioga virus with the members of the Guama group are presented. Both are believed to be new arboviruses in their groups.", "contents": "Bertioga (Guama group) and Anhembi (Bunyamwera group), two new arboviruses isolated in S\u00e3o Paulo, Brazil. Bertioga and Anhembi are two newly recognized arboviruses that were isolated in Sa\u00f5 Paulo, Brazil. Bertioga was isolated from sentinel mice exposed in a forest of that name, and was shown to belong serologically to the Guama group of arboviruses. Anhembi, the second virus described, was isolated from pools of mosquitoes (Phoniomyia pilicauda and trichoprosopon pallidiventer), and from a spiny rat (Proechimys iheringi), and was shown to be a new member of the Bunyamwera group. The viruses are sensitive to sodium desoxycholate and are filterable through a millipore membrane of 450 mum pore size. Both are pathogenic for suckling mice and grow well in Vero cells, producing clear cytopathic effects. Detailed antigenic comparisons of Anhembi virus with other members of the Bunyamwera group isolated in the Americas, and of Bertioga virus with the members of the Guama group are presented. Both are believed to be new arboviruses in their groups."}
{"id": "PMID:234207", "title": "Physiocochemical properties of a lipoprotein antigen of Echinococcus granulosus.", "content": "Molecular weight and optical properties of the lipoprotein B, the main antigen produced by the parasite in sheep hydatid fluid, have been determined. By sedimentation equilibrium studies, its molecular weight has been found equal to 120,000. Circular dichroism and optical rotatory dispersion spectra are consistent with an alpha-helix content of about 50%, and this ordered structure is not completely destroyed by dissociation in guanidinium choloride. The ORD spectrum is discussed in relation to the biological function of the lipoprotein antigen.", "contents": "Physiocochemical properties of a lipoprotein antigen of Echinococcus granulosus. Molecular weight and optical properties of the lipoprotein B, the main antigen produced by the parasite in sheep hydatid fluid, have been determined. By sedimentation equilibrium studies, its molecular weight has been found equal to 120,000. Circular dichroism and optical rotatory dispersion spectra are consistent with an alpha-helix content of about 50%, and this ordered structure is not completely destroyed by dissociation in guanidinium choloride. The ORD spectrum is discussed in relation to the biological function of the lipoprotein antigen."}
{"id": "PMID:234210", "title": "Hemodynamic responses to mechanical ventilation with PEEP: the effect of hypervolemia.", "content": "The hemodynamic effects of prolonged mechanical ventilation with positive end-expiratory pressure (PEEP), with and without blood volume augmentation, were studied in 18 beagles anesthetized with halothane (0.7 per cent end-tidal). Addition of 12 cm H2O PEEP during mechanical ventilation in normavolemic dogs was associated with reductions of transmural cardiac filling pressures, cardiac index and stroke index to 50 per cent of control values. Circulatory adaptation did not occur. Filling pressures and flow remained unchanged during the ensuing 8 hours when PEEP was maintained. They returned to control levels when PEEP was discontinued, except for the transmural right ventricular end-diastolic pressure, which remained elevated above control levels. Systemic vascular resistance was unchanged, but pulmonary vascular resistance doubled upon addition of PEEP. Following autologous whole blood transfusion (25 ml/kg) during mechanical ventilation with PEEP, cardiac index returned to, and remained at, control levels. After PEEP was discontinued, cardiac index increased acutely and remained elevated for the remainder of the study period (as long as 7 hours). Comparable transfusion during mechanical ventilation without PEEP elevated cardiac index only transiently. Right atrial, pulmonary capillary wedge, and right and left ventricular end-diastolic pressures showed marked increases relative to atmospheric with PEEP and after transfusion. Calculated transmural pressures demonstrated clear reductions with application of PEEP, followed by increases to control levels with transfusion and further increases to above control when PEEP was discontinued. Study of ventricular function curves revealed that changes in filling pressures and not to changes in ventricular contractility. Transmural pulmonary arterial diastolic pressure rose throughout the 12 hours of study, despite return of pulmonary vascular resistance to control level with removal of PEEP. Thus, acute decreases in cardiac filling pressure, cardiac index, and stroke index persist consequent to application of PEEP, and circulatory adaptation does not occur. The apparent hemodynamic deterioration may be reversed by blood volume augmentation, but when PEEP is discontinued, hypervolemia with consequent increases in filling pressures and a move along a ventricular function curve will occur. Changes in cardiac index will depend upon the overall state of right and left ventricular contractility.", "contents": "Hemodynamic responses to mechanical ventilation with PEEP: the effect of hypervolemia. The hemodynamic effects of prolonged mechanical ventilation with positive end-expiratory pressure (PEEP), with and without blood volume augmentation, were studied in 18 beagles anesthetized with halothane (0.7 per cent end-tidal). Addition of 12 cm H2O PEEP during mechanical ventilation in normavolemic dogs was associated with reductions of transmural cardiac filling pressures, cardiac index and stroke index to 50 per cent of control values. Circulatory adaptation did not occur. Filling pressures and flow remained unchanged during the ensuing 8 hours when PEEP was maintained. They returned to control levels when PEEP was discontinued, except for the transmural right ventricular end-diastolic pressure, which remained elevated above control levels. Systemic vascular resistance was unchanged, but pulmonary vascular resistance doubled upon addition of PEEP. Following autologous whole blood transfusion (25 ml/kg) during mechanical ventilation with PEEP, cardiac index returned to, and remained at, control levels. After PEEP was discontinued, cardiac index increased acutely and remained elevated for the remainder of the study period (as long as 7 hours). Comparable transfusion during mechanical ventilation without PEEP elevated cardiac index only transiently. Right atrial, pulmonary capillary wedge, and right and left ventricular end-diastolic pressures showed marked increases relative to atmospheric with PEEP and after transfusion. Calculated transmural pressures demonstrated clear reductions with application of PEEP, followed by increases to control levels with transfusion and further increases to above control when PEEP was discontinued. Study of ventricular function curves revealed that changes in filling pressures and not to changes in ventricular contractility. Transmural pulmonary arterial diastolic pressure rose throughout the 12 hours of study, despite return of pulmonary vascular resistance to control level with removal of PEEP. Thus, acute decreases in cardiac filling pressure, cardiac index, and stroke index persist consequent to application of PEEP, and circulatory adaptation does not occur. The apparent hemodynamic deterioration may be reversed by blood volume augmentation, but when PEEP is discontinued, hypervolemia with consequent increases in filling pressures and a move along a ventricular function curve will occur. Changes in cardiac index will depend upon the overall state of right and left ventricular contractility."}
{"id": "PMID:234211", "title": "The effect of pre-existing pulmonary vascular disease on the response to mechanical ventilation with PEEP following open-heart surgery.", "content": "The effects of mechanical ventilation with and without positive end-expiratory pressure (PEEP) on hemodynamic performance and blood-gas exchange were studied in ten patients following open-heart surgery. Ventilation at constant tidal volume (15 ml/kg body weight) with 10 cm H2O PEEP following aortic valve replacement (AVR) IN FIVE PATIENTs without pulmonary vascular disease was associated with the following significant changes: a rise in arterial Po2, a fall in the alveolar-arterial Po2 gradient when Fio2  = 1.0, decreases in calculated Qs/Qt and cardiac index. Using a similar pattern of ventilation following mitral valve replacement (MVR) in patients with elevated pulmonary vascular resistance, we found a significant decrease in cardiac index (but less than in the AVR group), a significant elevation of calculated physiologic deadspace (Vd/Vt) and no change in Qs/Qt. An hour after removal of PEEP, intravascular pressures, blood flow and blood-gas exchange values of all patients with AVR had returned to control levels; patients with MVR had persistently significantly low cardiac indices, while Vd/Vt returned to pre-PEEP values. These findings suggest that evaluation of responses to different ventilation patterns must take into account pre-existing V/Q abnormalities secondary to pulmonary vascular disease, particularly when these are secondary to chronic congestive heart failure. Following AVR, Qs/Qt changed in the same direction as cardiac index (CI) irrespective of ventilatory pattern: CI decreased and rose as CI increased. The authors conclude that with increasing severity of pulmonary vascular disease, changes in airway pressure will have an unpredictable effect on cardiac index unless the level of myocardial competence is taken into account. In the presence of ventricular failure, changes in pleural (and therefore transmural) pressures will be minimal compared with the high filling pressures and exert no influence on stroke volume. Although pulmonary venous hypertension was more pronounded in the MVR than in the AVR group, there was no significant difference between the postoperative values for Qs/Qt (Fio2 = 1.0), a condition probably fostered by marked differences in pre-existing V/Q.", "contents": "The effect of pre-existing pulmonary vascular disease on the response to mechanical ventilation with PEEP following open-heart surgery. The effects of mechanical ventilation with and without positive end-expiratory pressure (PEEP) on hemodynamic performance and blood-gas exchange were studied in ten patients following open-heart surgery. Ventilation at constant tidal volume (15 ml/kg body weight) with 10 cm H2O PEEP following aortic valve replacement (AVR) IN FIVE PATIENTs without pulmonary vascular disease was associated with the following significant changes: a rise in arterial Po2, a fall in the alveolar-arterial Po2 gradient when Fio2  = 1.0, decreases in calculated Qs/Qt and cardiac index. Using a similar pattern of ventilation following mitral valve replacement (MVR) in patients with elevated pulmonary vascular resistance, we found a significant decrease in cardiac index (but less than in the AVR group), a significant elevation of calculated physiologic deadspace (Vd/Vt) and no change in Qs/Qt. An hour after removal of PEEP, intravascular pressures, blood flow and blood-gas exchange values of all patients with AVR had returned to control levels; patients with MVR had persistently significantly low cardiac indices, while Vd/Vt returned to pre-PEEP values. These findings suggest that evaluation of responses to different ventilation patterns must take into account pre-existing V/Q abnormalities secondary to pulmonary vascular disease, particularly when these are secondary to chronic congestive heart failure. Following AVR, Qs/Qt changed in the same direction as cardiac index (CI) irrespective of ventilatory pattern: CI decreased and rose as CI increased. The authors conclude that with increasing severity of pulmonary vascular disease, changes in airway pressure will have an unpredictable effect on cardiac index unless the level of myocardial competence is taken into account. In the presence of ventricular failure, changes in pleural (and therefore transmural) pressures will be minimal compared with the high filling pressures and exert no influence on stroke volume. Although pulmonary venous hypertension was more pronounded in the MVR than in the AVR group, there was no significant difference between the postoperative values for Qs/Qt (Fio2 = 1.0), a condition probably fostered by marked differences in pre-existing V/Q."}
{"id": "PMID:234212", "title": "A program for calculation of intrapulmonary shunts, blood-gas and acid-base values with a programmable calculator.", "content": "With a desk-top, programmable calculator, it is now possible to do complex, previously time-consuming computations in the blood-gas laboratory. The authors have developed a program with the necessary algorithms for temperature correction of blood gases and calculation of acid-base variables and intrapulmonary shunt. It was necessary to develop formulas for the Po2 temperature-correction coefficient, the oxyhemoglobin-dissociation curve for adults (withe necessary adjustments for fetal blood), and changes in water vapor pressure due to variation in body temperature. Using this program in conjuction with a Monroe 1860-21 statistical programmable calculator, it is possible to temperature-correct pH,Pco2, and Po2. The machine will compute alveolar-arterial oxygen tension gradient, oxygen saturation (So2), oxygen content (Co2), actual HCO minus 3 and a modified base excess. If arterial blood and mixed venous blood are obtained, the calculator will print out intrapulmonary shunt data (Qs/Qt) and arteriovenous oxygen differences (a minus vDo2). There also is a formula to compute P50 if pH,Pco2,Po2, and measured So2 from two samples of tonometered blood (one above 50 per cent and one below 50 per cent saturation) are put into the calculator.", "contents": "A program for calculation of intrapulmonary shunts, blood-gas and acid-base values with a programmable calculator. With a desk-top, programmable calculator, it is now possible to do complex, previously time-consuming computations in the blood-gas laboratory. The authors have developed a program with the necessary algorithms for temperature correction of blood gases and calculation of acid-base variables and intrapulmonary shunt. It was necessary to develop formulas for the Po2 temperature-correction coefficient, the oxyhemoglobin-dissociation curve for adults (withe necessary adjustments for fetal blood), and changes in water vapor pressure due to variation in body temperature. Using this program in conjuction with a Monroe 1860-21 statistical programmable calculator, it is possible to temperature-correct pH,Pco2, and Po2. The machine will compute alveolar-arterial oxygen tension gradient, oxygen saturation (So2), oxygen content (Co2), actual HCO minus 3 and a modified base excess. If arterial blood and mixed venous blood are obtained, the calculator will print out intrapulmonary shunt data (Qs/Qt) and arteriovenous oxygen differences (a minus vDo2). There also is a formula to compute P50 if pH,Pco2,Po2, and measured So2 from two samples of tonometered blood (one above 50 per cent and one below 50 per cent saturation) are put into the calculator."}
{"id": "PMID:234213", "title": "Grain overload in cattle and sheep: changes in microbial populations in the cecum and rumen.", "content": "Samples from the rumen and cecum of cattle and sheep were cultured to determine changes in microbial populations resulting from overfeeding with grain. Before the animals were overfed, the predominant organisms from both sides were those that grew anaerobically on a relatively nonselective ruminal fluid medium and would not grow on selective mediums designed to culture lactobacilli, streptococci, coliforms, or Clostridium perfringens. By 24 hours after overfeeding, lactic acid bacteria had increased in numbers so that they were the most numerous organisms in both the rumen and the cecum. The concentrations of coliforms and C perfringens also increased after overfeeding and were generally higher in the cecum than in the rumen.", "contents": "Grain overload in cattle and sheep: changes in microbial populations in the cecum and rumen. Samples from the rumen and cecum of cattle and sheep were cultured to determine changes in microbial populations resulting from overfeeding with grain. Before the animals were overfed, the predominant organisms from both sides were those that grew anaerobically on a relatively nonselective ruminal fluid medium and would not grow on selective mediums designed to culture lactobacilli, streptococci, coliforms, or Clostridium perfringens. By 24 hours after overfeeding, lactic acid bacteria had increased in numbers so that they were the most numerous organisms in both the rumen and the cecum. The concentrations of coliforms and C perfringens also increased after overfeeding and were generally higher in the cecum than in the rumen."}
{"id": "PMID:234214", "title": "The effect of nitroglycerin in gas exchange on chronic obstructive pulmonary disease.", "content": "Nitroglycerin was administered to a group of 11 patients with chronic obstructive pulmonary disease in a dose of 0.4 mg sublingually. Arterial blood gases and blood pressure and pulse were measured at 5-min intervals for 30 min after nitroglycerin. There was a slight decrease in arterial O2 tension for the duration of the study; the maximal change was from a mean pre-nitroglycerin value of 53.5 mm Hg to 50.3 mm Hg at 20 min. In addition, there was a slight reduction in arterial CO2 tension and bicarbonate for 25 min. It is postulated that decreased O2 transport (due to increased hypoxemia and probably decreased cardiac output) plus hypocapnia were a sufficient stimulus to raise blood lactate. It is recommended that in patients receiving nitroglycerin who have obstructive airway disease, attention be directed toward the effect on arterial blood gases.", "contents": "The effect of nitroglycerin in gas exchange on chronic obstructive pulmonary disease. Nitroglycerin was administered to a group of 11 patients with chronic obstructive pulmonary disease in a dose of 0.4 mg sublingually. Arterial blood gases and blood pressure and pulse were measured at 5-min intervals for 30 min after nitroglycerin. There was a slight decrease in arterial O2 tension for the duration of the study; the maximal change was from a mean pre-nitroglycerin value of 53.5 mm Hg to 50.3 mm Hg at 20 min. In addition, there was a slight reduction in arterial CO2 tension and bicarbonate for 25 min. It is postulated that decreased O2 transport (due to increased hypoxemia and probably decreased cardiac output) plus hypocapnia were a sufficient stimulus to raise blood lactate. It is recommended that in patients receiving nitroglycerin who have obstructive airway disease, attention be directed toward the effect on arterial blood gases."}
{"id": "PMID:234219", "title": "Eosinophil polymorphonuclear leukocyte function in immediate hypersensitivity.", "content": "An eosinophil chemotactic factor of anaphylaxis (ECF-A), released along with other chemical mediators of immediate hypersensitivity from sensitized mast cells that have been challenged with specific antigen, is capable of selectively attracting eosinophils. The  rate and magnitude of tissue eosinophil influx may be enhanced by ascorbate and inhibited by the neutrophil immobilizing factor (NIF). Eosinophils may then exercise a local regulatory function. Phagocytosis or the action of ECF-A at high concentrations causes eosinophils to release arylsulfatase, which inactivates slow reacting substance of anaphylaxis (SRS-A). Additional possible functions of eosinophils may follow from their content of factors that inhibit histamine release or its mediator function, and the high levels of intracellular plasminogen and phospholipase B. Thus, the unique enzymes and factors released from eosinophils may form the basis of their role in immediate and subacute hypersensitivity reactions.", "contents": "Eosinophil polymorphonuclear leukocyte function in immediate hypersensitivity. An eosinophil chemotactic factor of anaphylaxis (ECF-A), released along with other chemical mediators of immediate hypersensitivity from sensitized mast cells that have been challenged with specific antigen, is capable of selectively attracting eosinophils. The  rate and magnitude of tissue eosinophil influx may be enhanced by ascorbate and inhibited by the neutrophil immobilizing factor (NIF). Eosinophils may then exercise a local regulatory function. Phagocytosis or the action of ECF-A at high concentrations causes eosinophils to release arylsulfatase, which inactivates slow reacting substance of anaphylaxis (SRS-A). Additional possible functions of eosinophils may follow from their content of factors that inhibit histamine release or its mediator function, and the high levels of intracellular plasminogen and phospholipase B. Thus, the unique enzymes and factors released from eosinophils may form the basis of their role in immediate and subacute hypersensitivity reactions."}
{"id": "PMID:234218", "title": "A comprehensive gas chromatography procedure for measurement of drugs in biological materials.", "content": "Procedures have been developed for the determination in serum and urine of 21 drugs which include all of the barbiturates, methyprylon, glutethimide, meprobamate, propoxyphene, methaqualone, primidone, diphenylhydantoin, methadone, codeine, morphine, amphetamine and methamphetamine. The method involves pipeting 1.0 ml of serum or urine into an extraction tube, adding an internal standard together with either a pH 4.9 or pH 8.3 buffer and extracting with chloroform. The drugs in the extract are concentrated by exaporation of the organic layer and identified and quantitated by gas-liquid chromatography (GLC) using a column packed with 3 percent OV 17. GLC analysis times are kept below seven minutes by using temperature programming which allows good separations of drugs of widely varying volatilities. All calculations are based on peak areas determined by an electronic integrator. Losses of drugs during extraction, evaporation and chromatography steps are compensated for by the use of internal standards. Actual extraction efficiencies of drugs from serum or urine range from 75 to 100 percent although recoveries, based on standards carried through the entire procedures, are quantitative. Precision (s.d.) based on replicate determinations is approximately plus or minus 0.2 mg per dl.", "contents": "A comprehensive gas chromatography procedure for measurement of drugs in biological materials. Procedures have been developed for the determination in serum and urine of 21 drugs which include all of the barbiturates, methyprylon, glutethimide, meprobamate, propoxyphene, methaqualone, primidone, diphenylhydantoin, methadone, codeine, morphine, amphetamine and methamphetamine. The method involves pipeting 1.0 ml of serum or urine into an extraction tube, adding an internal standard together with either a pH 4.9 or pH 8.3 buffer and extracting with chloroform. The drugs in the extract are concentrated by exaporation of the organic layer and identified and quantitated by gas-liquid chromatography (GLC) using a column packed with 3 percent OV 17. GLC analysis times are kept below seven minutes by using temperature programming which allows good separations of drugs of widely varying volatilities. All calculations are based on peak areas determined by an electronic integrator. Losses of drugs during extraction, evaporation and chromatography steps are compensated for by the use of internal standards. Actual extraction efficiencies of drugs from serum or urine range from 75 to 100 percent although recoveries, based on standards carried through the entire procedures, are quantitative. Precision (s.d.) based on replicate determinations is approximately plus or minus 0.2 mg per dl."}
{"id": "PMID:234242", "title": "A chemical approach to the fine structure of biomolecular complexes: the amino terminal region of the 50S ribosomal \"A\" protein from Bacillus stearothermophilus.", "content": "An experimental approach and methodology are described for determining the reactive properties and ionization constants of individual functional groups of proteins within biomolecular complexes. The ionization constants and reactivities of the methionyl-l amino terminus and the lysyl-3 residue of the alanine rich 50S ribosomal \"A\" protein from Bacillus stearothermophilus have been determined by an extension of the competitive labeling technique used by H. Kaplan, K. J. Stevenson, and B. S. Hartley ((1971), Biochem. J. 124, 289-299). This approach employs (1-14C)- and (3H)acetic anhydride in a double-labeling procedure. In 0.1 M KCl-0.02 M Mg2+-0.05 M Veronal at 10 degrees the methionyl-l amino terminus has a pKa of 7.5 and is exposed on the surface of the ribosome. The lysyl-3 has a pKa of 10 and is also exposed to solvent at the surface of the 50S subunit. Based on a linear free energy relationship (Bronsted plot) obtained with a series of standard amines the methionyl amino terminus has a substantially higher reactivity than expected from its ionization constant. The lysyl epsilon-amino group has the expected reactivity. The abnormally high reactivity of the methionyl amino terminus can only be accounted for by a specific interaction with other functional groups in the ribosome. These data support the proposal that the charged state of this residue is important in the structure and function of the \"A\" protein at the surface of the ribosome.", "contents": "A chemical approach to the fine structure of biomolecular complexes: the amino terminal region of the 50S ribosomal \"A\" protein from Bacillus stearothermophilus. An experimental approach and methodology are described for determining the reactive properties and ionization constants of individual functional groups of proteins within biomolecular complexes. The ionization constants and reactivities of the methionyl-l amino terminus and the lysyl-3 residue of the alanine rich 50S ribosomal \"A\" protein from Bacillus stearothermophilus have been determined by an extension of the competitive labeling technique used by H. Kaplan, K. J. Stevenson, and B. S. Hartley ((1971), Biochem. J. 124, 289-299). This approach employs (1-14C)- and (3H)acetic anhydride in a double-labeling procedure. In 0.1 M KCl-0.02 M Mg2+-0.05 M Veronal at 10 degrees the methionyl-l amino terminus has a pKa of 7.5 and is exposed on the surface of the ribosome. The lysyl-3 has a pKa of 10 and is also exposed to solvent at the surface of the 50S subunit. Based on a linear free energy relationship (Bronsted plot) obtained with a series of standard amines the methionyl amino terminus has a substantially higher reactivity than expected from its ionization constant. The lysyl epsilon-amino group has the expected reactivity. The abnormally high reactivity of the methionyl amino terminus can only be accounted for by a specific interaction with other functional groups in the ribosome. These data support the proposal that the charged state of this residue is important in the structure and function of the \"A\" protein at the surface of the ribosome."}
{"id": "PMID:234243", "title": "Synthesis of fluorescent organic phosphates and their equilibrium binding to bovine oxyhemoglobin.", "content": "Fluorescent organic phosphates, beta-naphthyl diphosphate, beta-naphthyl triphosphate, and beta-naphthyl tetraphosphate, were synthesized from beta-naphthyl monophosphate using Pi and N,N'-dicyclohexylcarbodiimide. These organic phosphates were interacted with bovine oxyhemoglobin, all in no buffer, 0.1 M NaCl, at 25 degrees and in the pH range 5.5-7.0. Equilibrium binding parameters were determined by measuring the fluorescence quenching upon their interaction. It is indicated that bovine oxyhemoglobin has more than one binding site, one of which is very strong. The strength of binding to the stronger site is in the order beta-naphthyl tetraphosphate greater than beta-naphthyl triphosphate greater than beta-naphthyl diphosphate. The logarithms of association constants of these phosphates depend linearly on the net charges of these phosphates at any pH. The results were accounted for by electrostatic effects using a simple charge model. In that model, the average positive net charges in oxyhemoglobin involved in the binding of beta-naphthyl phosphate are shown as a function of pH. It is shown that the binding of these fluorescent organic phosphates is prevented reversibly by the excess addition of nonfluorescent organic and iorganic phosphates, inositol hexaphosphate, tripolyphosphate, and pyrophosphate. Assuming competitive binding in a single strong site, the association constants of these nonfluorescent phosphates were also determined by measuring the recovery of the fluorescence intensity upon the release of fluorescent phosphates. At pH 6.18, the association constant of pyrophosphate is lower than that of tripolyphosphate by one order.", "contents": "Synthesis of fluorescent organic phosphates and their equilibrium binding to bovine oxyhemoglobin. Fluorescent organic phosphates, beta-naphthyl diphosphate, beta-naphthyl triphosphate, and beta-naphthyl tetraphosphate, were synthesized from beta-naphthyl monophosphate using Pi and N,N'-dicyclohexylcarbodiimide. These organic phosphates were interacted with bovine oxyhemoglobin, all in no buffer, 0.1 M NaCl, at 25 degrees and in the pH range 5.5-7.0. Equilibrium binding parameters were determined by measuring the fluorescence quenching upon their interaction. It is indicated that bovine oxyhemoglobin has more than one binding site, one of which is very strong. The strength of binding to the stronger site is in the order beta-naphthyl tetraphosphate greater than beta-naphthyl triphosphate greater than beta-naphthyl diphosphate. The logarithms of association constants of these phosphates depend linearly on the net charges of these phosphates at any pH. The results were accounted for by electrostatic effects using a simple charge model. In that model, the average positive net charges in oxyhemoglobin involved in the binding of beta-naphthyl phosphate are shown as a function of pH. It is shown that the binding of these fluorescent organic phosphates is prevented reversibly by the excess addition of nonfluorescent organic and iorganic phosphates, inositol hexaphosphate, tripolyphosphate, and pyrophosphate. Assuming competitive binding in a single strong site, the association constants of these nonfluorescent phosphates were also determined by measuring the recovery of the fluorescence intensity upon the release of fluorescent phosphates. At pH 6.18, the association constant of pyrophosphate is lower than that of tripolyphosphate by one order."}
{"id": "PMID:234244", "title": "Conformational isomerism and effective redox geometry in the oxidation of heme proteins by alkyl halides, cytochrome c, and cytochrome oxidase.", "content": "In contrast to its lethargy at physiological pH, horse heart cytochrome c can be oxidized at room temperature by the axial inner sphere oxidant bromomalononitrile (BMN) at higher acidities. The following stoichiometry obtains: 2Fe11 c + BrCH(CN2) + H+ leads to 2FeIII c + CH2(CN)2 + Br-, and the rate law is given by: rate = k2(FeIIc)(BMN). At an ionic strength of 1.0 (KCl), second-order rate constants vary from 300 l. per mol per sec (pH 2-3) to 0(pH 9). Below pH 6 there is a noticeable increase in rate with ionic strength while there is no specific salt effect for the process. At pH 7.4 there is no influence of added salt (0.01-1.0 M) upon the slow rate of reaction. The vast changes in rate occur over a pH region (3-6) in which only very minor changes in the visible spectrum of the cytochrome are manifest. The results are interpreted in terms of a conformational isomerism of cytochrome c in which the effective redox geometry alters from a predominantly \"short C\" form (in which an axial position is available for substitution) at lower pH's to a predominantly \"C\" form (axial positions encumbered) in the physiological region. At 5 degrees, pH 7.4, both hemes of beef heart cytochrome oxidase are oxidized by the addition of BMN (k2 = 29 plus or minus 3 l. per mol per sec). However, the reaction is inhibited by potassium cyanide and the protein containing iron(II) cyt alpha along with the cyano adduct of iron(II) or iron(III) cyt alpha3 is inert. The results demonstrate cytochrome alpha3 as the site of reaction and that alpha reduces alpha3 in the process. Cytochrome oxidase does catalyze the oxidation of cytochrome c with BMN as substrate. Taken together the results provide additional support for a recent theory and they demonstrate BMN to be an efficient probe for the effective redox geometry of a hemoprotein in solution.", "contents": "Conformational isomerism and effective redox geometry in the oxidation of heme proteins by alkyl halides, cytochrome c, and cytochrome oxidase. In contrast to its lethargy at physiological pH, horse heart cytochrome c can be oxidized at room temperature by the axial inner sphere oxidant bromomalononitrile (BMN) at higher acidities. The following stoichiometry obtains: 2Fe11 c + BrCH(CN2) + H+ leads to 2FeIII c + CH2(CN)2 + Br-, and the rate law is given by: rate = k2(FeIIc)(BMN). At an ionic strength of 1.0 (KCl), second-order rate constants vary from 300 l. per mol per sec (pH 2-3) to 0(pH 9). Below pH 6 there is a noticeable increase in rate with ionic strength while there is no specific salt effect for the process. At pH 7.4 there is no influence of added salt (0.01-1.0 M) upon the slow rate of reaction. The vast changes in rate occur over a pH region (3-6) in which only very minor changes in the visible spectrum of the cytochrome are manifest. The results are interpreted in terms of a conformational isomerism of cytochrome c in which the effective redox geometry alters from a predominantly \"short C\" form (in which an axial position is available for substitution) at lower pH's to a predominantly \"C\" form (axial positions encumbered) in the physiological region. At 5 degrees, pH 7.4, both hemes of beef heart cytochrome oxidase are oxidized by the addition of BMN (k2 = 29 plus or minus 3 l. per mol per sec). However, the reaction is inhibited by potassium cyanide and the protein containing iron(II) cyt alpha along with the cyano adduct of iron(II) or iron(III) cyt alpha3 is inert. The results demonstrate cytochrome alpha3 as the site of reaction and that alpha reduces alpha3 in the process. Cytochrome oxidase does catalyze the oxidation of cytochrome c with BMN as substrate. Taken together the results provide additional support for a recent theory and they demonstrate BMN to be an efficient probe for the effective redox geometry of a hemoprotein in solution."}
{"id": "PMID:234245", "title": "Interactions of aromatic residues of proteins with nucleic acids. Fluorescence studies of the binding of oligopeptides containing tryptophan and tyrosine residues to polynucleotides.", "content": "The binding of oligopeptides of general structure Lys-X-Lys (where X is an aromatic residue) to several polynucleotides has been studied by fluorescence spectroscopy. Two types of complexes are formed, both involving electrostatic interactions between lysyl residues and phosphate groups as shown by the ionic strength and pH dependence of binding. The fluorescence quantum yield of the first complex is identical with that of the free peptide. The other complex involves a stacking of the nucleic acid bases with the aromatic amino acid whose fluorescence is quenched. Fluorescence data have been quantitatively analyzed according to a model involving these two types of complexes. Association constants and the size of binding sites have been determined. Stacking interactions are favored in single-stranded polynucleotides as compared to double-stranded ones. A short oligopeptide such as Lys-X-Lys is thus able to distinguish between single-stranded and double-stranded nucleic acids. Fluorescence results are compared to those obtained by proton magnetic resonance and circular dichroism.", "contents": "Interactions of aromatic residues of proteins with nucleic acids. Fluorescence studies of the binding of oligopeptides containing tryptophan and tyrosine residues to polynucleotides. The binding of oligopeptides of general structure Lys-X-Lys (where X is an aromatic residue) to several polynucleotides has been studied by fluorescence spectroscopy. Two types of complexes are formed, both involving electrostatic interactions between lysyl residues and phosphate groups as shown by the ionic strength and pH dependence of binding. The fluorescence quantum yield of the first complex is identical with that of the free peptide. The other complex involves a stacking of the nucleic acid bases with the aromatic amino acid whose fluorescence is quenched. Fluorescence data have been quantitatively analyzed according to a model involving these two types of complexes. Association constants and the size of binding sites have been determined. Stacking interactions are favored in single-stranded polynucleotides as compared to double-stranded ones. A short oligopeptide such as Lys-X-Lys is thus able to distinguish between single-stranded and double-stranded nucleic acids. Fluorescence results are compared to those obtained by proton magnetic resonance and circular dichroism."}
{"id": "PMID:234246", "title": "Interaction of aromatic residues of proteins with nucleic acids. Circular dichroism studies of the binding of oligopeptides to poly(adenylic acid).", "content": "The binding of peptides containing lysyl and aromatic residues to poly(A) in its single-stranded form at pH 7 leads to a change of its circular dichroism (CD) spectrum, which is mainly due to the stacking of the aromatic amino acid with the bases of poly(A). Comparison is made between the binding of peptides having different primary structures which gives indications on the way the peptides bind to poly(A). A method is described which allows the calculation of the binding parameters from CD data. The magnitude of the association constant depends on the size of the aromatic ring and decreases in the order tryptophan greater than tyrosine greater than phenylalanine. The CD amplitude decreases linearly with the concentration of bound molecules. These results are discussed with respect to the role played by aromatic amino acids in complex formation between nucleic acids and proteins.", "contents": "Interaction of aromatic residues of proteins with nucleic acids. Circular dichroism studies of the binding of oligopeptides to poly(adenylic acid). The binding of peptides containing lysyl and aromatic residues to poly(A) in its single-stranded form at pH 7 leads to a change of its circular dichroism (CD) spectrum, which is mainly due to the stacking of the aromatic amino acid with the bases of poly(A). Comparison is made between the binding of peptides having different primary structures which gives indications on the way the peptides bind to poly(A). A method is described which allows the calculation of the binding parameters from CD data. The magnitude of the association constant depends on the size of the aromatic ring and decreases in the order tryptophan greater than tyrosine greater than phenylalanine. The CD amplitude decreases linearly with the concentration of bound molecules. These results are discussed with respect to the role played by aromatic amino acids in complex formation between nucleic acids and proteins."}
{"id": "PMID:234247", "title": "Initial reactions in the oxidation of naphthalene by Pseudomonas putida.", "content": "A strain of Pseudomonas putida that can utilize naphthalene as its sole source of carbon and energy was isolated from soil. A mutant strain of this organism, P. putida 119, when grown on glucose in the presence of naphthalene, accumulates optically pure (+)-cis-1(R),2(S)-dihydroxy-1,2-dihydronaphthalene in the culture medium. The cis relative stereochemistry in this molecule was established by nuclear magnetic resonance spectrometry. Radiochemical trapping experiments established that this cis dihydrodiol is an intermediate in the metabolism of naphthalene by P. Fluorescens (formerly ATCC, 17483), P. putida (ATCC, 17484), and a Pseudomonas species (NCIB 9816), as well as the parent strain of P. putida described in this report. Formation of the cis dihydrodiol is catalyzed by a dioxygenase which requires either NADH or NADPH as an electron donor. A double label procedure is described for determining the origin of oxygen in the cis dihydrodiol under conditions where this metabolite would not normally accumulate. Several aromatic hydrocarbons are oxidized by cell extracts prepared from naphthalene-grown cells of P. putida. The cis dihydrodiol is converted to 1,2-dihydroxynaphthalene by an NAD+-dependent dehydrogenase. This enzyme is specific for the (+) isomer of the dihydrodiol and shows a primary isotope effect when the dihydrodiol is substituted at C-2 with deuterium.", "contents": "Initial reactions in the oxidation of naphthalene by Pseudomonas putida. A strain of Pseudomonas putida that can utilize naphthalene as its sole source of carbon and energy was isolated from soil. A mutant strain of this organism, P. putida 119, when grown on glucose in the presence of naphthalene, accumulates optically pure (+)-cis-1(R),2(S)-dihydroxy-1,2-dihydronaphthalene in the culture medium. The cis relative stereochemistry in this molecule was established by nuclear magnetic resonance spectrometry. Radiochemical trapping experiments established that this cis dihydrodiol is an intermediate in the metabolism of naphthalene by P. Fluorescens (formerly ATCC, 17483), P. putida (ATCC, 17484), and a Pseudomonas species (NCIB 9816), as well as the parent strain of P. putida described in this report. Formation of the cis dihydrodiol is catalyzed by a dioxygenase which requires either NADH or NADPH as an electron donor. A double label procedure is described for determining the origin of oxygen in the cis dihydrodiol under conditions where this metabolite would not normally accumulate. Several aromatic hydrocarbons are oxidized by cell extracts prepared from naphthalene-grown cells of P. putida. The cis dihydrodiol is converted to 1,2-dihydroxynaphthalene by an NAD+-dependent dehydrogenase. This enzyme is specific for the (+) isomer of the dihydrodiol and shows a primary isotope effect when the dihydrodiol is substituted at C-2 with deuterium."}
{"id": "PMID:234248", "title": "The antibody-enzyme analogy. Comparison of enzymes and antibodies specific for phosphopyridoxyltyrosine.", "content": "Reduced Schiff base compounds of pyridoxal-P and tyrosine, which were used to induce specific antibodies described in the preceding article (V. Raso and B. D. Stolar, Biochemistry, 1975), caused active site-directed inhibition of tyrosine transaminase and tyrosine decarboxylase. The antibodies, studied as analogs of enzymes, were able to bind an unsaturated Schiff base catalytic intermediate, as shown by equilibrium dialysis and absorbance difference spectroscopy. Schiff base formation can proceed while the pyridoxal-P and tyrosine are within the antibody combining site, but the rate of this bimolecular condensation within the sites was not greater than the rate in free solution. Antibody did effect a small rate enhancement for the pyridoxal-P-catalyzed transamination of L-tyrosine. These results are discussed in light of current ideas in the mechanisms of enzyme catalysis.", "contents": "The antibody-enzyme analogy. Comparison of enzymes and antibodies specific for phosphopyridoxyltyrosine. Reduced Schiff base compounds of pyridoxal-P and tyrosine, which were used to induce specific antibodies described in the preceding article (V. Raso and B. D. Stolar, Biochemistry, 1975), caused active site-directed inhibition of tyrosine transaminase and tyrosine decarboxylase. The antibodies, studied as analogs of enzymes, were able to bind an unsaturated Schiff base catalytic intermediate, as shown by equilibrium dialysis and absorbance difference spectroscopy. Schiff base formation can proceed while the pyridoxal-P and tyrosine are within the antibody combining site, but the rate of this bimolecular condensation within the sites was not greater than the rate in free solution. Antibody did effect a small rate enhancement for the pyridoxal-P-catalyzed transamination of L-tyrosine. These results are discussed in light of current ideas in the mechanisms of enzyme catalysis."}
{"id": "PMID:234249", "title": "Properties of the stable aerobic and anaerobic half-reduced states of NADPH-cytochrome c reductase.", "content": "The microsomal flavoprotein, NADPH-cytochrome c reductase, has been reexamined to determine: (1) the nature of the flavine bound to the enzyme and (2) the oxidation-reduction state of the \"half-reduced\" form of the flavoprotein. Iyanagi and Mason (Iyanagi, T., and Mason, H.S. (1973), Biochemistry 12, 2297) have recently proposed that NADPH-cytochrome c reductase contains both FAD and FMN as prosthetic groups in lieu of FAD as the sole constituent, as suggested by all previous studies of this enzyme. The data presented herein, utilizing the recently published fluorometric procedure of Faeder and Siegel (Faeder, E. J., and Siegle, L. M. (1973), Anal. Biochem. 53, 332) for the determination of FAD and FMN in mixtures, confirm the conclusions of Iyanagi and Mason for both rat and pig liver reductase preparations. Data for other flavoproteins are also presented. Iyanagi and Mason have also concluded that the air-stable \"semiquinone\" is a form of NADPH-cytochrome c reductase reduced by one electron per two falvines (F-FH). The present studies, however, do not agree with this conclusion, but instead support our previous results which indicate that both the aerobic and anaerobic half-reduced states of this flavoprotein exist in the two-electron reduced form (FH-FH). Removal of NADP+ does not affect the spectrum of the air-stable half-reduced form of the flavoprotein, nor does it affect the back titration of this intermediate by potassium ferricyanide. The possible implications of these observations on the catalytic cycle of the flavines of NADPH-cytochrome c reductase are discussed.", "contents": "Properties of the stable aerobic and anaerobic half-reduced states of NADPH-cytochrome c reductase. The microsomal flavoprotein, NADPH-cytochrome c reductase, has been reexamined to determine: (1) the nature of the flavine bound to the enzyme and (2) the oxidation-reduction state of the \"half-reduced\" form of the flavoprotein. Iyanagi and Mason (Iyanagi, T., and Mason, H.S. (1973), Biochemistry 12, 2297) have recently proposed that NADPH-cytochrome c reductase contains both FAD and FMN as prosthetic groups in lieu of FAD as the sole constituent, as suggested by all previous studies of this enzyme. The data presented herein, utilizing the recently published fluorometric procedure of Faeder and Siegel (Faeder, E. J., and Siegle, L. M. (1973), Anal. Biochem. 53, 332) for the determination of FAD and FMN in mixtures, confirm the conclusions of Iyanagi and Mason for both rat and pig liver reductase preparations. Data for other flavoproteins are also presented. Iyanagi and Mason have also concluded that the air-stable \"semiquinone\" is a form of NADPH-cytochrome c reductase reduced by one electron per two falvines (F-FH). The present studies, however, do not agree with this conclusion, but instead support our previous results which indicate that both the aerobic and anaerobic half-reduced states of this flavoprotein exist in the two-electron reduced form (FH-FH). Removal of NADP+ does not affect the spectrum of the air-stable half-reduced form of the flavoprotein, nor does it affect the back titration of this intermediate by potassium ferricyanide. The possible implications of these observations on the catalytic cycle of the flavines of NADPH-cytochrome c reductase are discussed."}
{"id": "PMID:234250", "title": "Kinetic studies on the mechanism of pepsin action.", "content": "The linear noncompetitive inhibition of the pepsin-catalyzed hydrolysis of Ac-Phe-Phe-Gly at pH 2.1 by L-Ac-Phe, L-Ac-Phe-NH2, and L-Ac-Phe-OEt has been claimed to substantiate the ordered release of products specified by the amino-enzyme mechanism for pepsin action. According to this interpretation, the binding of inhibitor to free enzyme and the amino-enzyme intermediate (Scheme I) generates the observed inhibition pattern. The proposition is valid only if a simple alternative explanation for the kinetic data, Scheme II, can be disproved. Scheme II attributes the inhibition pattern to the binding of inhibitor to free enzyme and the enzyme-substrate (Michaelis) complex. The experiments reported here have enabled us to distinguish between the two mechanisms. The pepsin-catalyzed hydrolyses of Ac-Phe-Trp, Z-H'IS-Phe-Trp, Z-Gly-His-Phe-Trp, and Z-Ala-His-Phe-Trp at pH 1.8 occur exclusively at the Phe-Trp bond and must yield the same amino-enzyme, E-Trp, if it is implicated. Under these circumstances, Scheme I requires that a plot of 1/kc vs. (I)o for the four substrates and a given noncompetitive inhibitor provide a set of four parallel lines. Scheme II predicts that the four lines generally will not be parallel. L-Ac-Phe, L-Ac-Phe-NH2, L-Ac-Phe-OMe, and D-Ac-Phe act as linear noncompetitive inhibitors for the pepsin-catalyzed hydrolysis of the four Trp-containing substrates. The plot of 1/kc vs. (I)o for each inhibitor results in a set of four nonparallel lines. Therefore Scheme II must be correct and the detection of noncompetitive inhibition accompanying the pepsin-catalyzed hydrolysis of peptides offers no insight into the merits of the amino-enzyme hypothesis.", "contents": "Kinetic studies on the mechanism of pepsin action. The linear noncompetitive inhibition of the pepsin-catalyzed hydrolysis of Ac-Phe-Phe-Gly at pH 2.1 by L-Ac-Phe, L-Ac-Phe-NH2, and L-Ac-Phe-OEt has been claimed to substantiate the ordered release of products specified by the amino-enzyme mechanism for pepsin action. According to this interpretation, the binding of inhibitor to free enzyme and the amino-enzyme intermediate (Scheme I) generates the observed inhibition pattern. The proposition is valid only if a simple alternative explanation for the kinetic data, Scheme II, can be disproved. Scheme II attributes the inhibition pattern to the binding of inhibitor to free enzyme and the enzyme-substrate (Michaelis) complex. The experiments reported here have enabled us to distinguish between the two mechanisms. The pepsin-catalyzed hydrolyses of Ac-Phe-Trp, Z-H'IS-Phe-Trp, Z-Gly-His-Phe-Trp, and Z-Ala-His-Phe-Trp at pH 1.8 occur exclusively at the Phe-Trp bond and must yield the same amino-enzyme, E-Trp, if it is implicated. Under these circumstances, Scheme I requires that a plot of 1/kc vs. (I)o for the four substrates and a given noncompetitive inhibitor provide a set of four parallel lines. Scheme II predicts that the four lines generally will not be parallel. L-Ac-Phe, L-Ac-Phe-NH2, L-Ac-Phe-OMe, and D-Ac-Phe act as linear noncompetitive inhibitors for the pepsin-catalyzed hydrolysis of the four Trp-containing substrates. The plot of 1/kc vs. (I)o for each inhibitor results in a set of four nonparallel lines. Therefore Scheme II must be correct and the detection of noncompetitive inhibition accompanying the pepsin-catalyzed hydrolysis of peptides offers no insight into the merits of the amino-enzyme hypothesis."}
{"id": "PMID:234251", "title": "Resonance Raman investigation of an enzyme-inhibitor complex.", "content": "The resonance Raman spectrum has been recorded for two different binary complexes formed between 2-carboxy-2'-hydroxy-5'-sulfoformazylbenzene (zincon) and liver alcohol dehydrogenase. The shifts in the zincon spectrum upon complexation with enzyme in one complex are similar to those in model compounds containing azo or formazyl linkages upon complexation of these with zinc. The results are interpreted in terms of complexation of zincon to a zinc atom at the enzyme active site. Since zincon is a coenzyme competitive inhibitor, it is probably bound at or near the coenzyme binding site; the results of this study, therefore, are useful in understanding the chemistry of zinc at the enzyme active site.", "contents": "Resonance Raman investigation of an enzyme-inhibitor complex. The resonance Raman spectrum has been recorded for two different binary complexes formed between 2-carboxy-2'-hydroxy-5'-sulfoformazylbenzene (zincon) and liver alcohol dehydrogenase. The shifts in the zincon spectrum upon complexation with enzyme in one complex are similar to those in model compounds containing azo or formazyl linkages upon complexation of these with zinc. The results are interpreted in terms of complexation of zincon to a zinc atom at the enzyme active site. Since zincon is a coenzyme competitive inhibitor, it is probably bound at or near the coenzyme binding site; the results of this study, therefore, are useful in understanding the chemistry of zinc at the enzyme active site."}
{"id": "PMID:234252", "title": "Characterization of the mycoplasma membrane proteins. V. Release and localization of membrane-bound enzymes in Acholeplasma laidlawii.", "content": "The peripheral membrane protein fraction released by washing Acholeplasma laidlawii membranes with low-ionic strength buffers contained about 50% of the total membrane-bound ribonuclease and deoxyribonuclease activities. The ATPase, NADH oxidase and p-nitrophenylphosphatase activities remained bound to the membrane even when EDTA was added to the wash fluids, and thus appear to belong to the integral membrane protein group. Serving as a marker for peripheral membrane proteins, the membrane-bound ribonuclease activity was solubilized by bile salts much more effectively than the integral membrane-bound enzymes. On the other hand, the solubilized ribonuclease showed a much lower capacity to reaggregate with other solubilized membrane components to membranous structures. Yet, most of the ribonuclease molecules which were bound to the reaggregated membranes could not be released by low-ionic strength buffer. The reaggregated membranes differed from the native membranes in the absence of particles on their fracture faces obtained by freeze cleaving, and by their much higher labeling by the [125-I]lactoperoxidase iodination system. These results suggest that most of the proteins are exposed on the reaggregated membrane surfaces, with very little, if any, protein embedded in its lipid bilayer core. Enzyme disposition in the A. laidlawii membrane was studied by comparing the activity of isolated membranes with that of membranes of intact cells after treatment with pronase or with an antiserum to membranes. The data indicate the asymmetrical disposition of these activities, the ATPase and NADH oxidase being localized on the inner membrane surface, while the nucleases are exposed on the external membrane surface.", "contents": "Characterization of the mycoplasma membrane proteins. V. Release and localization of membrane-bound enzymes in Acholeplasma laidlawii. The peripheral membrane protein fraction released by washing Acholeplasma laidlawii membranes with low-ionic strength buffers contained about 50% of the total membrane-bound ribonuclease and deoxyribonuclease activities. The ATPase, NADH oxidase and p-nitrophenylphosphatase activities remained bound to the membrane even when EDTA was added to the wash fluids, and thus appear to belong to the integral membrane protein group. Serving as a marker for peripheral membrane proteins, the membrane-bound ribonuclease activity was solubilized by bile salts much more effectively than the integral membrane-bound enzymes. On the other hand, the solubilized ribonuclease showed a much lower capacity to reaggregate with other solubilized membrane components to membranous structures. Yet, most of the ribonuclease molecules which were bound to the reaggregated membranes could not be released by low-ionic strength buffer. The reaggregated membranes differed from the native membranes in the absence of particles on their fracture faces obtained by freeze cleaving, and by their much higher labeling by the [125-I]lactoperoxidase iodination system. These results suggest that most of the proteins are exposed on the reaggregated membrane surfaces, with very little, if any, protein embedded in its lipid bilayer core. Enzyme disposition in the A. laidlawii membrane was studied by comparing the activity of isolated membranes with that of membranes of intact cells after treatment with pronase or with an antiserum to membranes. The data indicate the asymmetrical disposition of these activities, the ATPase and NADH oxidase being localized on the inner membrane surface, while the nucleases are exposed on the external membrane surface."}
{"id": "PMID:234254", "title": "Metabolism and properties of 3-methoxy-4-hydroxyphenyl-pyruvate; a metabolite of dihydroxyphenylalanine.", "content": "The pathway of 3,4-dihydroxyphenylalanine undergoing metabolism via transamination and subsequent oxidative rearrangement to 2,4,5-trihydroxy-phenylacetate was investigated. 3-Methoxytyrosine does not pursue an identical course, since its corresponding keto acid is not subject to action of p-hydroxy-phenylpyruvate hydroxylase. The radiochemical synthesis of 3-methoxy-4-hydroxy[carboxy-14C] pyruvate was accomplished. This metabolite was used to demonstrate that this keto acid does not proceed through oxidative rearrangement both in vitro and in vivo. The keto acid was found to be a competitive inhibitor of the hydroxylase and can help account for some of the metabolites observed in the urine of patients treated with 3,4-dihydroxyphenylalanine.", "contents": "Metabolism and properties of 3-methoxy-4-hydroxyphenyl-pyruvate; a metabolite of dihydroxyphenylalanine. The pathway of 3,4-dihydroxyphenylalanine undergoing metabolism via transamination and subsequent oxidative rearrangement to 2,4,5-trihydroxy-phenylacetate was investigated. 3-Methoxytyrosine does not pursue an identical course, since its corresponding keto acid is not subject to action of p-hydroxy-phenylpyruvate hydroxylase. The radiochemical synthesis of 3-methoxy-4-hydroxy[carboxy-14C] pyruvate was accomplished. This metabolite was used to demonstrate that this keto acid does not proceed through oxidative rearrangement both in vitro and in vivo. The keto acid was found to be a competitive inhibitor of the hydroxylase and can help account for some of the metabolites observed in the urine of patients treated with 3,4-dihydroxyphenylalanine."}
{"id": "PMID:234255", "title": "[Isoenzymes of carbonic anhydrase of an euryhaline fish. Variations related to the osmoregulation].", "content": "A chemical study of carbonic anhydrase (EC 4.2.1.1) from the red blood cells and the gills of an euryhaline fish (Anguilla anguilla) is presented. Animals adapted to fresh water were compared to those adapted to sea water. The physiochemical constants of the various molecular formsisolated by chromatography and isoelectric focusing were determined; isoelectric pH, molecular weight, and the Km and V/E of the enzyme dehydration activity were compared. In both red cells and gills of fish adapted in either media various forms were isolated, characterized by different enzymatic kinetics (high- and low- activity forms) but having the same molecular weight (27 250). Some isoenzymes isolated from the gills differed significantly from those isolated from the red cells. Adaptation to fresh water or sea water is accompanied by modifications in the distribution of the isoenzymes in both red cells and gills: adaptation to sea water is characterized by a shift of the molecular forms towards an isoelectric pH higher than pH equals 6. The role of these enzymes is discussed under both a physiological and biochemical point of view in relation to the electrolyte exchange across fish gill. The origin of the different molecular forms of the carbonic anhydrase is discussed in relation to the prevailing theories on this subject.", "contents": "[Isoenzymes of carbonic anhydrase of an euryhaline fish. Variations related to the osmoregulation]. A chemical study of carbonic anhydrase (EC 4.2.1.1) from the red blood cells and the gills of an euryhaline fish (Anguilla anguilla) is presented. Animals adapted to fresh water were compared to those adapted to sea water. The physiochemical constants of the various molecular formsisolated by chromatography and isoelectric focusing were determined; isoelectric pH, molecular weight, and the Km and V/E of the enzyme dehydration activity were compared. In both red cells and gills of fish adapted in either media various forms were isolated, characterized by different enzymatic kinetics (high- and low- activity forms) but having the same molecular weight (27 250). Some isoenzymes isolated from the gills differed significantly from those isolated from the red cells. Adaptation to fresh water or sea water is accompanied by modifications in the distribution of the isoenzymes in both red cells and gills: adaptation to sea water is characterized by a shift of the molecular forms towards an isoelectric pH higher than pH equals 6. The role of these enzymes is discussed under both a physiological and biochemical point of view in relation to the electrolyte exchange across fish gill. The origin of the different molecular forms of the carbonic anhydrase is discussed in relation to the prevailing theories on this subject."}
{"id": "PMID:234259", "title": "[Solubilization and several properties of NAD-glucohydrolase isolated from rabbit heart].", "content": "Methods of isolation of NAD-glucohydrolase from the fraction of heart microsomes were searched for. NAD-glucohydrolase proved to pass into a soluble state under the effect of phospholipase A, triton X-100 and Na cholate. NAD-glucohydrolase was found to possess peculiar properties; it reversibly became denatured under the effect of 6M urea, but failed to become inactivated with own substrate (NAD) at pH 8.0. In case of  NAD-ases isolated from other sources the reversible denaturation by means of urea as a rule correlated with the enzyme inactivation in the presence of NAD at pH 8.0.", "contents": "[Solubilization and several properties of NAD-glucohydrolase isolated from rabbit heart]. Methods of isolation of NAD-glucohydrolase from the fraction of heart microsomes were searched for. NAD-glucohydrolase proved to pass into a soluble state under the effect of phospholipase A, triton X-100 and Na cholate. NAD-glucohydrolase was found to possess peculiar properties; it reversibly became denatured under the effect of 6M urea, but failed to become inactivated with own substrate (NAD) at pH 8.0. In case of  NAD-ases isolated from other sources the reversible denaturation by means of urea as a rule correlated with the enzyme inactivation in the presence of NAD at pH 8.0."}
{"id": "PMID:234256", "title": "[Letter: Laser light scattering study of the effect of extracellular medium properties on the myofibrillar structure of muscle fibers].", "content": "Mean myofibrillar radii are calculated from the curvity of the correlation function computed from equatorial light scattering distribution by means of Hankel integral transformation. Light scattering is measured for the same muscle fibre in the media of various ionic strength or pH. The light scattering experimental results are compared with X-ray diffraction data and our theoretical predictions.", "contents": "[Letter: Laser light scattering study of the effect of extracellular medium properties on the myofibrillar structure of muscle fibers]. Mean myofibrillar radii are calculated from the curvity of the correlation function computed from equatorial light scattering distribution by means of Hankel integral transformation. Light scattering is measured for the same muscle fibre in the media of various ionic strength or pH. The light scattering experimental results are compared with X-ray diffraction data and our theoretical predictions."}
{"id": "PMID:234257", "title": "Cctionic selectivity of bimolecular membranes in the presence of nystatin and amphotericin B.", "content": "Ergosterin or 7-dehydrocholesterin-containing artificial membranes are selectively permeable for cations of alkaline metals in aqueous solutions of nistatin and amphotericine B. Membrane permeability changes spontaneously within several tens of minutes from the cation to the anion one. A decrease of temperature, an increase of medium pH or introduction of dimethylsulphoxide into aqueous solution inhibit, while the addition of calcium accelerate this transition.", "contents": "Cctionic selectivity of bimolecular membranes in the presence of nystatin and amphotericin B. Ergosterin or 7-dehydrocholesterin-containing artificial membranes are selectively permeable for cations of alkaline metals in aqueous solutions of nistatin and amphotericine B. Membrane permeability changes spontaneously within several tens of minutes from the cation to the anion one. A decrease of temperature, an increase of medium pH or introduction of dimethylsulphoxide into aqueous solution inhibit, while the addition of calcium accelerate this transition."}
{"id": "PMID:234258", "title": "[Effect of cation concentration and medium pH on the distance between 2 lipid bilayers in the contact zone].", "content": "Dependence of the distance between contacting bilayer lipid membranes on the concentration of mono-and bivalent cations and medium pH has been measured by an optimcal method. It has been show that the presence of cations in the medium decreases the equilibrium distance between contacting membranes, the effect being more pronounced for bivalent Ca.", "contents": "[Effect of cation concentration and medium pH on the distance between 2 lipid bilayers in the contact zone]. Dependence of the distance between contacting bilayer lipid membranes on the concentration of mono-and bivalent cations and medium pH has been measured by an optimcal method. It has been show that the presence of cations in the medium decreases the equilibrium distance between contacting membranes, the effect being more pronounced for bivalent Ca."}
{"id": "PMID:234261", "title": "Pathology of modified graft-versus-host disease in bone marrow allografted monkeys treated with antilymphocyte serum.", "content": "Lethally irradiated rhesus monkeys were used for bone marrow allografting and autografting. Monkeys receiving allogeneic bone marrow developed acute graft-versus-host reaction (GVHR) and had a mean survival time of 9.1 days as compared to autografted monkeys which survived above 500 days. Treatment with antilymphocyte sera (ALS) before allografting modified the GVHR and extended the survival time to an average of 43 days. Histologically, such animals showed evidence of \"chronic\" GVHR and septicemia secondary to a lack in lymphoreticular recovery. Subsequently, severe GI-tract infections followed which usually served as portal of entry for septicemia.", "contents": "Pathology of modified graft-versus-host disease in bone marrow allografted monkeys treated with antilymphocyte serum. Lethally irradiated rhesus monkeys were used for bone marrow allografting and autografting. Monkeys receiving allogeneic bone marrow developed acute graft-versus-host reaction (GVHR) and had a mean survival time of 9.1 days as compared to autografted monkeys which survived above 500 days. Treatment with antilymphocyte sera (ALS) before allografting modified the GVHR and extended the survival time to an average of 43 days. Histologically, such animals showed evidence of \"chronic\" GVHR and septicemia secondary to a lack in lymphoreticular recovery. Subsequently, severe GI-tract infections followed which usually served as portal of entry for septicemia."}
{"id": "PMID:234262", "title": "Experimental salicylate intoxication in young baboons. A preliminary report.", "content": "Salicylate intoxication has been investigated in young baboons. The results of these studies are similar to these previously obtained in man. Acidosis appears to be of considerable importance in the pathogenesis of infantile salicylism as it enhances the passage of salicylate into the CSF. The CSF concentration of salicylate seems to be of major physiologic importance in this condition. Moreover, the serum concentration of free salicylate correlates more closely with the CSF concentration of salicylate than does the total serum concentration of salicylate.", "contents": "Experimental salicylate intoxication in young baboons. A preliminary report. Salicylate intoxication has been investigated in young baboons. The results of these studies are similar to these previously obtained in man. Acidosis appears to be of considerable importance in the pathogenesis of infantile salicylism as it enhances the passage of salicylate into the CSF. The CSF concentration of salicylate seems to be of major physiologic importance in this condition. Moreover, the serum concentration of free salicylate correlates more closely with the CSF concentration of salicylate than does the total serum concentration of salicylate."}
{"id": "PMID:234263", "title": "Fluorescent dye method for determination of the bilirubin-binding capacity of serum albumin.", "content": "A simple, rapid microfluorometric method utilizing a fluorescent dye, Direct Yellow 7, for quantitative measurement of serum albumin-binding capacity for bilirubin has been developed. The dye binds exclusively to serum albumin with enhancement of fluorescence. The dye shares bilirubin-binding sites on albumin with up to 2 mols of bilirubin per mol of albumin with differing affinities to the first and second sites. Lowered pH reduces albumin-binding capacity and exposure to light increases binding capacity of icteric sera. The binding capacity of adult human sera is greater than that of human cord sera or purified human serum albumin compared on albumin molar basis.", "contents": "Fluorescent dye method for determination of the bilirubin-binding capacity of serum albumin. A simple, rapid microfluorometric method utilizing a fluorescent dye, Direct Yellow 7, for quantitative measurement of serum albumin-binding capacity for bilirubin has been developed. The dye binds exclusively to serum albumin with enhancement of fluorescence. The dye shares bilirubin-binding sites on albumin with up to 2 mols of bilirubin per mol of albumin with differing affinities to the first and second sites. Lowered pH reduces albumin-binding capacity and exposure to light increases binding capacity of icteric sera. The binding capacity of adult human sera is greater than that of human cord sera or purified human serum albumin compared on albumin molar basis."}
{"id": "PMID:234264", "title": "Aminopyrine--an effective modifier of liver and serum gamma glutamyl transpeptidase.", "content": "Serum activities of gamma glutamyl transpeptidase, alanine and aspartate aminotransferases, and alkaline phosphatase were determined in children on long-term treatment with aminopyrine. Gamma glutamyl transpeptidase activity was increased up to 15 times above the upper normal limit in children, who received aminopyrine for two weeks or longer. Livers of rats treated with aminopyrine (600 mg/kg/day for 18 to 25 days) had an exceedingly increased activity of gamma glutamyl transpeptidase and a slightly elevated microsomal cytochrome P-450 content. Apparently isolated enhancement of serum gamma glutamyl transpeptidase during aminopyrine medication represents a drug-induced increase of microsomal liver enzymes without clinical relevance and without evidence of damage of liver cells.", "contents": "Aminopyrine--an effective modifier of liver and serum gamma glutamyl transpeptidase. Serum activities of gamma glutamyl transpeptidase, alanine and aspartate aminotransferases, and alkaline phosphatase were determined in children on long-term treatment with aminopyrine. Gamma glutamyl transpeptidase activity was increased up to 15 times above the upper normal limit in children, who received aminopyrine for two weeks or longer. Livers of rats treated with aminopyrine (600 mg/kg/day for 18 to 25 days) had an exceedingly increased activity of gamma glutamyl transpeptidase and a slightly elevated microsomal cytochrome P-450 content. Apparently isolated enhancement of serum gamma glutamyl transpeptidase during aminopyrine medication represents a drug-induced increase of microsomal liver enzymes without clinical relevance and without evidence of damage of liver cells."}
{"id": "PMID:234266", "title": "Long-term beta blockade: possible protection from myocardial infarction.", "content": "The clinical behaviour of 90 patients on beta-blocking drugs for established coronary heart disease who were admitted to a coronary care unit with prolonged ischaemic myocardial pain was compared with that of 90 similar patients not on this therapy.  Transmural myocardial infarction was confirmed in 30 of the patients on beta-blockers and in 62 controls.  A diagnosis of myocardial necrosis without infarction was made in 20 patients on beta-blockers and in 14 controls.  Coronary insufficiency was diagnosed in 40 patients on beta-blockers and in 14 controls.  The incidence of simus bradycardia, hypotension, syncope, and radiological pulmonary oedema was similar in the two groups.  Established beta-blockade, therefore, has not been shown to prejudice the outcome of patients with coronary heart disease admitted to hospital with prolonged ischaemic myocardial pain.  On the contrary, it may protect some patients from the development of a myocardial infarction.", "contents": "Long-term beta blockade: possible protection from myocardial infarction. The clinical behaviour of 90 patients on beta-blocking drugs for established coronary heart disease who were admitted to a coronary care unit with prolonged ischaemic myocardial pain was compared with that of 90 similar patients not on this therapy.  Transmural myocardial infarction was confirmed in 30 of the patients on beta-blockers and in 62 controls.  A diagnosis of myocardial necrosis without infarction was made in 20 patients on beta-blockers and in 14 controls.  Coronary insufficiency was diagnosed in 40 patients on beta-blockers and in 14 controls.  The incidence of simus bradycardia, hypotension, syncope, and radiological pulmonary oedema was similar in the two groups.  Established beta-blockade, therefore, has not been shown to prejudice the outcome of patients with coronary heart disease admitted to hospital with prolonged ischaemic myocardial pain.  On the contrary, it may protect some patients from the development of a myocardial infarction."}
{"id": "PMID:234267", "title": "Failure of secretin release in patients with duodenal ulcer.", "content": "The release of secretin was studied in 12 normal subjects and 23 patients suffering from proved duodenal ulceration. After infusing acid directly into the duodenum mean plasma levels (plus or minus S.E.M.) of secretin rose in normal subjects to 52.6 plus or minus 4.8 ng/1 at six minutes but to only 37.5 plus or minus 3.6 ng/1 in duodenal-ulcer patients, a significant difference. The impairment of secretin release was as great in patients with a recent onset as in those who had had symptoms of a duodenal ulcer for a long time, raising the possibility of it being a primary defect. Patients who smoked 20 or more cigarettes a day had a particularly reduced secretin release, in accord with the greater incidence of ulcers in heavy smokers.", "contents": "Failure of secretin release in patients with duodenal ulcer. The release of secretin was studied in 12 normal subjects and 23 patients suffering from proved duodenal ulceration. After infusing acid directly into the duodenum mean plasma levels (plus or minus S.E.M.) of secretin rose in normal subjects to 52.6 plus or minus 4.8 ng/1 at six minutes but to only 37.5 plus or minus 3.6 ng/1 in duodenal-ulcer patients, a significant difference. The impairment of secretin release was as great in patients with a recent onset as in those who had had symptoms of a duodenal ulcer for a long time, raising the possibility of it being a primary defect. Patients who smoked 20 or more cigarettes a day had a particularly reduced secretin release, in accord with the greater incidence of ulcers in heavy smokers."}
{"id": "PMID:234268", "title": "Results of adrenal surgery in patients with hypertension, aldosterone excess, and low plasma renin concentration.", "content": "Fifty patients with hypertension, aldosterone excess, and low plasma renin concentration underwent adrenal surgery.  There was a highly significant fall in mean systolic and diastolic pressures after the operation.  The mean postoperative diastolic pressure fell to strictly normal levels, however, in only 19 out of 38 patients from whom an adrenocortical adenoma was removed and in only two out of 10 non-tumour patients.  There was a significant correlation between the fall in blood pressure during spironolactone treatment and after adrenal surgery though levels were generally slightly lower during the former therapy. It is suggested that removal of an aldosterone-producing adenoma is the treatment of choice provided a good preoperative hypotensive response to spironolactone occurs, while the treatment of choice for non-tumour patients is often long-term spironolactone.", "contents": "Results of adrenal surgery in patients with hypertension, aldosterone excess, and low plasma renin concentration. Fifty patients with hypertension, aldosterone excess, and low plasma renin concentration underwent adrenal surgery.  There was a highly significant fall in mean systolic and diastolic pressures after the operation.  The mean postoperative diastolic pressure fell to strictly normal levels, however, in only 19 out of 38 patients from whom an adrenocortical adenoma was removed and in only two out of 10 non-tumour patients.  There was a significant correlation between the fall in blood pressure during spironolactone treatment and after adrenal surgery though levels were generally slightly lower during the former therapy. It is suggested that removal of an aldosterone-producing adenoma is the treatment of choice provided a good preoperative hypotensive response to spironolactone occurs, while the treatment of choice for non-tumour patients is often long-term spironolactone."}
{"id": "PMID:234270", "title": "The pharmacological and anatomical substrates of the amphetamine response in the rat.", "content": "Bilateral 6-hydroxydopamine microinjections into the substantia nigra abolished both the locomotor and stereotyped responses to d-amphetamine in adult rats.  The lesions resulted in a depletion of over 99 per cent of striatal tyrosine hydroxylase activity (indicating a near total lesion of the nigro-striatal dopamine pathway) as well as severe noradrenaline depletions.  However, lesion of the dorsal or ventral noradrenergic pathways resulted in similar noradrenaline depletions but with no effect on striatal tyrosine hydroxylase levels and without the concomitant blockage of the amphetamine response.  The substantia nigra lesioned rats were behaviourally supersensitive to apomorphine and L-DOPA and did not show a locomotor response to cocaine.  The substantia nigra lesioned rats were not aphagic or adipsic.  It was concluded that both the locomotor and stereotyped responses induced by amphetamine are dependent on the functional integrity of the nigro-striatal dopamine pathway.", "contents": "The pharmacological and anatomical substrates of the amphetamine response in the rat. Bilateral 6-hydroxydopamine microinjections into the substantia nigra abolished both the locomotor and stereotyped responses to d-amphetamine in adult rats.  The lesions resulted in a depletion of over 99 per cent of striatal tyrosine hydroxylase activity (indicating a near total lesion of the nigro-striatal dopamine pathway) as well as severe noradrenaline depletions.  However, lesion of the dorsal or ventral noradrenergic pathways resulted in similar noradrenaline depletions but with no effect on striatal tyrosine hydroxylase levels and without the concomitant blockage of the amphetamine response.  The substantia nigra lesioned rats were behaviourally supersensitive to apomorphine and L-DOPA and did not show a locomotor response to cocaine.  The substantia nigra lesioned rats were not aphagic or adipsic.  It was concluded that both the locomotor and stereotyped responses induced by amphetamine are dependent on the functional integrity of the nigro-striatal dopamine pathway."}
{"id": "PMID:234271", "title": "Compartmentation of amino acid metabolism in the rat dorsal root ganglion; a metabolic and autoradiographic study.", "content": "The incorporation of radioactivity into glutamate, glutamine, GABA and other amino acids was followed after incubation of desheathed rat dorsal root ganglia in media containing [14C]glucose or [14C]acetate. The results indicated that [14C]glucose was incorporated into a large pool of glutamate, but that this glutamate pool did not synthesize glutamine or GABA to any great extent. [14C]Acetate, on the other hand, was incorporated into a small glutamate pool which was readily converted to glutamine, and which synthesized GABA to a greater extent than the large pool. Light microscopic autoradiography of ganglia incubated with [14C]glucose or [14C]acetate confirmed that the small pool labelled by acetate was probably associated with satellite glial cells, while the large pool was located within the ganglion neurons. The results are discussed within the context of previous work on compartmentation of glutamate metabolism in the central nervous system.", "contents": "Compartmentation of amino acid metabolism in the rat dorsal root ganglion; a metabolic and autoradiographic study. The incorporation of radioactivity into glutamate, glutamine, GABA and other amino acids was followed after incubation of desheathed rat dorsal root ganglia in media containing [14C]glucose or [14C]acetate. The results indicated that [14C]glucose was incorporated into a large pool of glutamate, but that this glutamate pool did not synthesize glutamine or GABA to any great extent. [14C]Acetate, on the other hand, was incorporated into a small glutamate pool which was readily converted to glutamine, and which synthesized GABA to a greater extent than the large pool. Light microscopic autoradiography of ganglia incubated with [14C]glucose or [14C]acetate confirmed that the small pool labelled by acetate was probably associated with satellite glial cells, while the large pool was located within the ganglion neurons. The results are discussed within the context of previous work on compartmentation of glutamate metabolism in the central nervous system."}
{"id": "PMID:234272", "title": "Ionic excitation of a clone of mouse neuroblastoma.", "content": "The electrical properties and the possible regulation of these properties were studied by means of intracellular microelectrode recordings in cells of mouse neuroblastoma clone N1E-115. This clone has high levels of tyrosine hydroxylase and regulates this enzyme. Cells treated for 24 h with 4 muM aminopterin followed by at least 5 days in culture developed rhythmic discharge of action potentials when superfused with phosphate-buffered saline containing less than 0.2 mM calcium or less than 0.2 mM calcium and zero potassium. This ionic excitation occurred in no cells at less than 5 days after treatment with aminopterin but at 5 days or more after treatment, 20% of cells responded to low calcium while 52% responded to low calcium and zero potassium. Concomitant with the development of a susceptibility to ionic excitation was an increase in the average resting membrane potential and morphologic maturation. This ionic excitation of cultured mouse neuroblastoma cells may be useful for studying biochemical events associated with repetitive discharge of action potentials.", "contents": "Ionic excitation of a clone of mouse neuroblastoma. The electrical properties and the possible regulation of these properties were studied by means of intracellular microelectrode recordings in cells of mouse neuroblastoma clone N1E-115. This clone has high levels of tyrosine hydroxylase and regulates this enzyme. Cells treated for 24 h with 4 muM aminopterin followed by at least 5 days in culture developed rhythmic discharge of action potentials when superfused with phosphate-buffered saline containing less than 0.2 mM calcium or less than 0.2 mM calcium and zero potassium. This ionic excitation occurred in no cells at less than 5 days after treatment with aminopterin but at 5 days or more after treatment, 20% of cells responded to low calcium while 52% responded to low calcium and zero potassium. Concomitant with the development of a susceptibility to ionic excitation was an increase in the average resting membrane potential and morphologic maturation. This ionic excitation of cultured mouse neuroblastoma cells may be useful for studying biochemical events associated with repetitive discharge of action potentials."}
{"id": "PMID:234274", "title": "Comparison of the effects of biogenic amines on cyclic GMP and cycle AMP levels in mouse cerebellum in vitro.", "content": "Norepinephrine (NE) elevates levels of both 3',5'-guanosine monophosphate (cyclic GMP) and 3',5'-adenosine monophosphate (cyclic AMP) in incubated slices of mouse cerebellum. As little as 1 muM NE is capable of increasing the level of either cyclic nucleotide. Maximal elevations of cyclic AMP and cyclic GMP levels produced by NE are 15- to 40-fold and 2- to 4-fold, respectively. Dopamine, serotonin and histamine, other biogenic amines considered to be neurotransmitters in CNS, have no effect on mouse cerebellum cyclic nucleotide levels except at relatively high (1 mM) concentrations. NE-induced accumulation of cyclic GMP, but not cyclic AMP, is blocked by omission of Ca2+ from the incubation media. Theophylline does not alter the effect of this catecholamine on either cyclic nucleotide. In tissue slices incubated in buffered sucrose or in choline-Krebs buffer, NE is still capable of increasing both cyclic GMP and cyclic AMP levels; however, these elevations are less than those observed in brain slices incubated in Krebs-Ringer buffer. NE, in combination with glutamate, produces supra-additive elevations of both cyclic GMP and cyclic AMP levels. However, NE in combination with adenosine or high levels of K+ only has a synergistic effect on cyclic AMP and not on cyclic AMP and not on cyclic GMP combination. The elevation of cyclic AMP levels produced by NE appears to be mediated via both alpha- and beta-adrenergic receptor sites. In contrast, the receptor site(s) mediating cyclic AMP accumulation do not appear to be either typical alpha- or beta-adrenergic receptors.", "contents": "Comparison of the effects of biogenic amines on cyclic GMP and cycle AMP levels in mouse cerebellum in vitro. Norepinephrine (NE) elevates levels of both 3',5'-guanosine monophosphate (cyclic GMP) and 3',5'-adenosine monophosphate (cyclic AMP) in incubated slices of mouse cerebellum. As little as 1 muM NE is capable of increasing the level of either cyclic nucleotide. Maximal elevations of cyclic AMP and cyclic GMP levels produced by NE are 15- to 40-fold and 2- to 4-fold, respectively. Dopamine, serotonin and histamine, other biogenic amines considered to be neurotransmitters in CNS, have no effect on mouse cerebellum cyclic nucleotide levels except at relatively high (1 mM) concentrations. NE-induced accumulation of cyclic GMP, but not cyclic AMP, is blocked by omission of Ca2+ from the incubation media. Theophylline does not alter the effect of this catecholamine on either cyclic nucleotide. In tissue slices incubated in buffered sucrose or in choline-Krebs buffer, NE is still capable of increasing both cyclic GMP and cyclic AMP levels; however, these elevations are less than those observed in brain slices incubated in Krebs-Ringer buffer. NE, in combination with glutamate, produces supra-additive elevations of both cyclic GMP and cyclic AMP levels. However, NE in combination with adenosine or high levels of K+ only has a synergistic effect on cyclic AMP and not on cyclic AMP and not on cyclic GMP combination. The elevation of cyclic AMP levels produced by NE appears to be mediated via both alpha- and beta-adrenergic receptor sites. In contrast, the receptor site(s) mediating cyclic AMP accumulation do not appear to be either typical alpha- or beta-adrenergic receptors."}
{"id": "PMID:234275", "title": "The effects of psychomotor stimulants on stereotypy and locomotor activity in socially-deprived and control rats.", "content": "Using measures of locomotor activity and stereotypy, dose-response curves to several psychomotor stimulant drugs were obtained on rats reared in deprived or normal environments. At both 0.5 and 1.5 mg/kg d-amphetamine, the deprived rats exhibited more intense stereotyped behavior than the control rats. At 5.0 mg/kg, both groups showed maximum response. However, there was no significant difference between the two groups in locomotor response. A similar pattern of results was found for pipradrol, cocaine, and apomorphine. The findings show that different social and environmental experience can modify the response to dopaminergic stimulating agents. The results also suggest that stereotyped behavior should not be considered on the same continuum as locomotor activity. These two behaviors may be mediated by different mechanisms.", "contents": "The effects of psychomotor stimulants on stereotypy and locomotor activity in socially-deprived and control rats. Using measures of locomotor activity and stereotypy, dose-response curves to several psychomotor stimulant drugs were obtained on rats reared in deprived or normal environments. At both 0.5 and 1.5 mg/kg d-amphetamine, the deprived rats exhibited more intense stereotyped behavior than the control rats. At 5.0 mg/kg, both groups showed maximum response. However, there was no significant difference between the two groups in locomotor response. A similar pattern of results was found for pipradrol, cocaine, and apomorphine. The findings show that different social and environmental experience can modify the response to dopaminergic stimulating agents. The results also suggest that stereotyped behavior should not be considered on the same continuum as locomotor activity. These two behaviors may be mediated by different mechanisms."}
{"id": "PMID:234276", "title": "Effects of dopaminergic receptor agonists and antagonists on the activity of the neo-striatal cholinergic system.", "content": "The effects of various neuroleptics and of apomorphine on the metabolism of ACh were examined in the neostriatum of the rat. For this purpose, a specific radio-enzymatic assay for brain ACh was used. This method is based on the preliminary purification of the choline esters by liquid cation exchange, separation of choline and ACh on thin layer chromatography plates, hydrolysis of ACh then reactylation of the choline moiety with a purified and stabilized rat brain choline acetyltransferase. The rat neostriatal ACh levels were decreased by neuroleptics of the phenothiazine and butyrophenone type and increased by apomorphine. An \"in vivo\" estimation of the rate of utilization of ACh was obtained by measuring the decline in neostriatal ACh content following the local microinjection of hemicholinium-3. This compound blocked almost totally the synthesis of ACh in these conditions. Chlorpromazine (15 mg/kg) enhanced neo-striatal ACh utilization and apomorphine (10 mg/kg) antagonized this effect. Neuroleptics did not effect ACh levels in the parietal cerebral cortex and the hippocampal formation. The modifications of the activity of neostriatal cholinergic neurons by chlorpromazine and apomorphine were still observed following the degeneration of the nigro-neostriatal dopaminergic fibers induced by the injection of 6-hydroxydopamine into the substantia nigra. The results strongly suggest that dopaminergic receptors as defined by their pharmacological interaction with neuroleptics and apomorphine are localized on neostriatal ACh neurons.", "contents": "Effects of dopaminergic receptor agonists and antagonists on the activity of the neo-striatal cholinergic system. The effects of various neuroleptics and of apomorphine on the metabolism of ACh were examined in the neostriatum of the rat. For this purpose, a specific radio-enzymatic assay for brain ACh was used. This method is based on the preliminary purification of the choline esters by liquid cation exchange, separation of choline and ACh on thin layer chromatography plates, hydrolysis of ACh then reactylation of the choline moiety with a purified and stabilized rat brain choline acetyltransferase. The rat neostriatal ACh levels were decreased by neuroleptics of the phenothiazine and butyrophenone type and increased by apomorphine. An \"in vivo\" estimation of the rate of utilization of ACh was obtained by measuring the decline in neostriatal ACh content following the local microinjection of hemicholinium-3. This compound blocked almost totally the synthesis of ACh in these conditions. Chlorpromazine (15 mg/kg) enhanced neo-striatal ACh utilization and apomorphine (10 mg/kg) antagonized this effect. Neuroleptics did not effect ACh levels in the parietal cerebral cortex and the hippocampal formation. The modifications of the activity of neostriatal cholinergic neurons by chlorpromazine and apomorphine were still observed following the degeneration of the nigro-neostriatal dopaminergic fibers induced by the injection of 6-hydroxydopamine into the substantia nigra. The results strongly suggest that dopaminergic receptors as defined by their pharmacological interaction with neuroleptics and apomorphine are localized on neostriatal ACh neurons."}
{"id": "PMID:234277", "title": "Ontogeny of the induction of tyrosine hydroxylase by reserpine in the superior cervical ganglion, nucleus locus coeruleus and adrenal gland.", "content": "The ontogeny of the induction of tyrosine hydroxylase by reserpine has been studied in the superior cervical ganglion, adrenal gland and nucleus locus coeruleus of the rat. The inductive response developed gradually over a period of days in all 3 areas. However, the onset of induction occurred at markedly different times in these regions, being present from day 2 of life, the earilest time tested, in the adrenal, day 6 in the locus coeruleus and day 24 in the ganglion. In the ganglion even extremely high, toxic doses of reserpine failed to induce the enzyme during the first 3 weeks of life. Decentralization studies indicated that the ganglion was functionally innervated at this time. Moreover, the onset of induction was not time-locked to a specific phase of the postnatal development of tyrosine hydroxylase activity in the areas examined. It is probable that the development of inducibility reflects maturation of mechanisms intrinsic to the adrenergic cell, and this timetable is different for cells in different areas.", "contents": "Ontogeny of the induction of tyrosine hydroxylase by reserpine in the superior cervical ganglion, nucleus locus coeruleus and adrenal gland. The ontogeny of the induction of tyrosine hydroxylase by reserpine has been studied in the superior cervical ganglion, adrenal gland and nucleus locus coeruleus of the rat. The inductive response developed gradually over a period of days in all 3 areas. However, the onset of induction occurred at markedly different times in these regions, being present from day 2 of life, the earilest time tested, in the adrenal, day 6 in the locus coeruleus and day 24 in the ganglion. In the ganglion even extremely high, toxic doses of reserpine failed to induce the enzyme during the first 3 weeks of life. Decentralization studies indicated that the ganglion was functionally innervated at this time. Moreover, the onset of induction was not time-locked to a specific phase of the postnatal development of tyrosine hydroxylase activity in the areas examined. It is probable that the development of inducibility reflects maturation of mechanisms intrinsic to the adrenergic cell, and this timetable is different for cells in different areas."}
{"id": "PMID:234281", "title": "On GABA metabolism in the gliocyte cells of the rat pineal gland.", "content": "The uptake of the inhibitory transmitter substance gamma-aminobutyric acid (GABA) into the adult rat pineal gland was studied autoradiographically using both light and electron microscopy. The sites of GABA uptake were shown to be exclusively present in the gliocyte cells of the gland following both in vitro incubation with tritiated GABA and after in vivo administration of the amino acid by intra-arterial injection. Both the pinealocyte cells and the numerous sympathetic axons in the gland were devoid of silver grains. Preliminary biochemical studies indicated that the gliocyte uptake process for GABA resembles that in the satellite glia of the sensory ganglia but differed from that in slices of the cerebral cortex. Evidence is also presented which shows the pineal gland to contain endogenous GABA and the enzymes directly associated with its in vivo metabolism, L-glutamate-1-carboxylase (EC 4.1.1.15) (GAD) and GABA-2-oxoglutarate aminotransferase (EC 2.6.1.19) (GABA-T). Furthermore, a 3-fold rise in endogenous GABA occurred in the pineal after inhibition of GABA-catabolism as would be expected if the GABA-shunt pathway was functionally active in the oxidative metabolism of the pineal gland.", "contents": "On GABA metabolism in the gliocyte cells of the rat pineal gland. The uptake of the inhibitory transmitter substance gamma-aminobutyric acid (GABA) into the adult rat pineal gland was studied autoradiographically using both light and electron microscopy. The sites of GABA uptake were shown to be exclusively present in the gliocyte cells of the gland following both in vitro incubation with tritiated GABA and after in vivo administration of the amino acid by intra-arterial injection. Both the pinealocyte cells and the numerous sympathetic axons in the gland were devoid of silver grains. Preliminary biochemical studies indicated that the gliocyte uptake process for GABA resembles that in the satellite glia of the sensory ganglia but differed from that in slices of the cerebral cortex. Evidence is also presented which shows the pineal gland to contain endogenous GABA and the enzymes directly associated with its in vivo metabolism, L-glutamate-1-carboxylase (EC 4.1.1.15) (GAD) and GABA-2-oxoglutarate aminotransferase (EC 2.6.1.19) (GABA-T). Furthermore, a 3-fold rise in endogenous GABA occurred in the pineal after inhibition of GABA-catabolism as would be expected if the GABA-shunt pathway was functionally active in the oxidative metabolism of the pineal gland."}
{"id": "PMID:234283", "title": "The detection of transmissible gastroenteritis viral antigens by immunodiffusion.", "content": "Parathyroid (PT) glands from 20-day-old embryonic chicks cultured in a chemically defined medium secreted a stimulator of in vitro bone resorption. This stimulator was presumed to be parathyroid hormone (PTH) because: 1) the in vitro dose response curve was parallel to that obtained with bovine PTH; 2) the activity was eluted on Sephadex G-1--chromatography at a postition similar to that for PTH; and 3) the material produced hypercalcemia in vivo in chicks. The amount of PTH-activity secreted was inversely proportional to the calcium concentration of the medium over the range of 0.75-2.25 mM. The chick PT glands also secreted an inhibitor of PTH-stimulated bone resorption in vitro. This inhibitor was presumed to be calcitonin (CT) because: 1) the in vitro dose-response curve was parallel to that obtained with synthetic salmon CT; 2) the activity was eluted on Sephadex G-50 chromatography at a position similar to that for salmon CT; and 3) the material produced hypocalcemia in vivo in rats. In contrast to what would be expected for CT secretion, the CT-activity was secreted by the PT glands in response to a low, not high calcium concentration. The data suggest that the secretion of avian PTH is similar to that of the mammalian hormone, and that the ultimobranchialectomized chick with an intact parathyroid gland may not be deficient in CT.", "contents": "The detection of transmissible gastroenteritis viral antigens by immunodiffusion. Parathyroid (PT) glands from 20-day-old embryonic chicks cultured in a chemically defined medium secreted a stimulator of in vitro bone resorption. This stimulator was presumed to be parathyroid hormone (PTH) because: 1) the in vitro dose response curve was parallel to that obtained with bovine PTH; 2) the activity was eluted on Sephadex G-1--chromatography at a postition similar to that for PTH; and 3) the material produced hypercalcemia in vivo in chicks. The amount of PTH-activity secreted was inversely proportional to the calcium concentration of the medium over the range of 0.75-2.25 mM. The chick PT glands also secreted an inhibitor of PTH-stimulated bone resorption in vitro. This inhibitor was presumed to be calcitonin (CT) because: 1) the in vitro dose-response curve was parallel to that obtained with synthetic salmon CT; 2) the activity was eluted on Sephadex G-50 chromatography at a position similar to that for salmon CT; and 3) the material produced hypocalcemia in vivo in rats. In contrast to what would be expected for CT secretion, the CT-activity was secreted by the PT glands in response to a low, not high calcium concentration. The data suggest that the secretion of avian PTH is similar to that of the mammalian hormone, and that the ultimobranchialectomized chick with an intact parathyroid gland may not be deficient in CT."}
{"id": "PMID:234284", "title": "Pharmacokinetics of phenylbutazone and oxyphenabutazone in the pig.", "content": "The kinetics of phenylbutazone (pbz) and its main metabolite oxyphenbutazone (oxpbz) were investigated in seven pigs in order to determine if this animal might serve as a model for human investigations. The study was performed in two stages, one as single dose experiments using intravenous injection, the second as infusion experiments. The rate of elimination for both compounds was demonstrated to be much faster than in man. Similar results have been observed in several other animal species. The degree of protein binding (pbz 98%, ox-pbz 97%), the apparent specific volume of distribution (pbz 0.18 1/kg, ox-pbz 0.28 1/kg) and the renal clearance were found to be similar to results obtained in man and rat. Ox-pbz had a higher renal clearance (0.13 ml/min/kg) than pbz (0.003 ml/min/kg) but still the renal excretion constituted only a small fraction of the total elimination (pbz 0.5%, ox-pbz 5%). Provided real steady state conditions were obtained during the infusion experiments calculations based on the results from the single dose experiments in the same animal revealed that between 20 and 60% of the injected pbz was metabolized to the ring-hydroxylation product (ox-pbz). It is concluded that the pig model is not superior to other animal models for studies of pbz/ox-pbz. The rapid elimination pattern is the main problem in relation to human investigations.", "contents": "Pharmacokinetics of phenylbutazone and oxyphenabutazone in the pig. The kinetics of phenylbutazone (pbz) and its main metabolite oxyphenbutazone (oxpbz) were investigated in seven pigs in order to determine if this animal might serve as a model for human investigations. The study was performed in two stages, one as single dose experiments using intravenous injection, the second as infusion experiments. The rate of elimination for both compounds was demonstrated to be much faster than in man. Similar results have been observed in several other animal species. The degree of protein binding (pbz 98%, ox-pbz 97%), the apparent specific volume of distribution (pbz 0.18 1/kg, ox-pbz 0.28 1/kg) and the renal clearance were found to be similar to results obtained in man and rat. Ox-pbz had a higher renal clearance (0.13 ml/min/kg) than pbz (0.003 ml/min/kg) but still the renal excretion constituted only a small fraction of the total elimination (pbz 0.5%, ox-pbz 5%). Provided real steady state conditions were obtained during the infusion experiments calculations based on the results from the single dose experiments in the same animal revealed that between 20 and 60% of the injected pbz was metabolized to the ring-hydroxylation product (ox-pbz). It is concluded that the pig model is not superior to other animal models for studies of pbz/ox-pbz. The rapid elimination pattern is the main problem in relation to human investigations."}
{"id": "PMID:234285", "title": "Cultivation and maintenance of Sphaerophorus necrophorus. Part II: Influence of pH on maximum growth and acid production in Medium 156.", "content": "Sphaerophorus necrophorus was grown in Medium 156 at 40 pH values ranging from 4.93 to 9.46. Growth occurred between pH 5.30 and 9.28. The optimum pH for maximum growth was 6.84 while the optimum pH for acid production was 7.70. At pH 7.70 acid production was more than double that at pH 6.84 during a 12 hour incubation period. Thus, maximum growth occurs at one pH and maximum acid producation at another. Since the two optima are different, acid production should be evaluated only when: 1. an optimum medium is employed, 2. the optimum pH for acid production is employed. 3. the incubation period necessary for maximum acid production has elapsed before the test is conducted.", "contents": "Cultivation and maintenance of Sphaerophorus necrophorus. Part II: Influence of pH on maximum growth and acid production in Medium 156. Sphaerophorus necrophorus was grown in Medium 156 at 40 pH values ranging from 4.93 to 9.46. Growth occurred between pH 5.30 and 9.28. The optimum pH for maximum growth was 6.84 while the optimum pH for acid production was 7.70. At pH 7.70 acid production was more than double that at pH 6.84 during a 12 hour incubation period. Thus, maximum growth occurs at one pH and maximum acid producation at another. Since the two optima are different, acid production should be evaluated only when: 1. an optimum medium is employed, 2. the optimum pH for acid production is employed. 3. the incubation period necessary for maximum acid production has elapsed before the test is conducted."}
{"id": "PMID:234287", "title": "In vitro activity of clindamycin and other antimicrobials against gram-positive bacteria and Hemophilus influenzae.", "content": "Seven antimicrobials--clindamycin, penicillin, ampicillin, cloxacillin, erythromycin, lincomycin and cephalexin--were found to have a high degree of activity in vitro against 256 isolates of gram-positive bacteria and Hemophilus influenzae. Clindamycin was clearly superior against staphylococci and 3.12 mug/ml or less of clindamycin inhibited all 35 isolates of H. influenzae. Synergism was not demonstrated when clindamycin was tested in combination with sulfisoxazole or sulfamethoxazole by either the agar dilution or 24-hour growth curve method. This was true for penicillin as well, and the effect was independent of sulfonamide sensitivity. The erythromycin-sulfonamide combination was synergistic against 6 of 10 strains studied by the growth curve method; this effect was not demonstrable by the agar dilution method.", "contents": "In vitro activity of clindamycin and other antimicrobials against gram-positive bacteria and Hemophilus influenzae. Seven antimicrobials--clindamycin, penicillin, ampicillin, cloxacillin, erythromycin, lincomycin and cephalexin--were found to have a high degree of activity in vitro against 256 isolates of gram-positive bacteria and Hemophilus influenzae. Clindamycin was clearly superior against staphylococci and 3.12 mug/ml or less of clindamycin inhibited all 35 isolates of H. influenzae. Synergism was not demonstrated when clindamycin was tested in combination with sulfisoxazole or sulfamethoxazole by either the agar dilution or 24-hour growth curve method. This was true for penicillin as well, and the effect was independent of sulfonamide sensitivity. The erythromycin-sulfonamide combination was synergistic against 6 of 10 strains studied by the growth curve method; this effect was not demonstrable by the agar dilution method."}
{"id": "PMID:234288", "title": "Some aspects of medical management of gastrointestinal disease. I.", "content": "Among drugs recently introduced into Canada for treatment of gastrointestinal disease are carbenoxolone sodium (used in treating gastric ulcer) and metoclopramide hydrochloride (which modifies upper gastrointestinal tract motility). A third drug, lactulose (useful in treating hepatic encephalopathy), will soon be available. Clinical experience with these drugs has been most extensive in Europe. In a new class of agents are histamine H2-receptor antagonists, which are currently under clinical trial. These drugs are the most potent inhibitors of gastric acid secretion yet investigated, and are potentially the most exciting agents to appear in many years. Part I of this paper is a review of the actions, clinical use, side effects, and dosage and administration of these new drugs.", "contents": "Some aspects of medical management of gastrointestinal disease. I. Among drugs recently introduced into Canada for treatment of gastrointestinal disease are carbenoxolone sodium (used in treating gastric ulcer) and metoclopramide hydrochloride (which modifies upper gastrointestinal tract motility). A third drug, lactulose (useful in treating hepatic encephalopathy), will soon be available. Clinical experience with these drugs has been most extensive in Europe. In a new class of agents are histamine H2-receptor antagonists, which are currently under clinical trial. These drugs are the most potent inhibitors of gastric acid secretion yet investigated, and are potentially the most exciting agents to appear in many years. Part I of this paper is a review of the actions, clinical use, side effects, and dosage and administration of these new drugs."}
{"id": "PMID:234290", "title": "Renal tubular acidosis during therapy for diabetic ketoacidosis.", "content": "A young woman presented with typical diabetic ketoacidosis. Five hours after insulin had been given hyperchloremic metabolic acidosis developed. This could not be attributed to gastrointestinal loss of bacarbonate, ingestion of HCI or carbonic anhydrase inhibitor, or the administered fluids and electrolytes. The combination of hyperchloremic metabolic acidosis and a urine pH of 5.6 during acidemia prompted specific studies that established the presence of disorders of renal acidification. A transient defect of hydrogen ion secretion in the distal nephron was suggested by the decrease in urine-blood Pco-2 gradient after administration of sodium bicarbonate. Proximal renal tubular acidosis was indicated by the reduced bicarbonate threshold that persisted for approximately 7 weeks.", "contents": "Renal tubular acidosis during therapy for diabetic ketoacidosis. A young woman presented with typical diabetic ketoacidosis. Five hours after insulin had been given hyperchloremic metabolic acidosis developed. This could not be attributed to gastrointestinal loss of bacarbonate, ingestion of HCI or carbonic anhydrase inhibitor, or the administered fluids and electrolytes. The combination of hyperchloremic metabolic acidosis and a urine pH of 5.6 during acidemia prompted specific studies that established the presence of disorders of renal acidification. A transient defect of hydrogen ion secretion in the distal nephron was suggested by the decrease in urine-blood Pco-2 gradient after administration of sodium bicarbonate. Proximal renal tubular acidosis was indicated by the reduced bicarbonate threshold that persisted for approximately 7 weeks."}
{"id": "PMID:234291", "title": "Immunotherapy of melanoma with BCG: two fatalities following intralesional injection.", "content": "Two fatalities are reported following intralesional injection of BCG for immunotherapy of malignant melanoma. In both cases the terminal events were characterized by high fevers, major clotting defects, hypotension, and anuria, suggesting that the mechanism was hypersensitivity to BCG.", "contents": "Immunotherapy of melanoma with BCG: two fatalities following intralesional injection. Two fatalities are reported following intralesional injection of BCG for immunotherapy of malignant melanoma. In both cases the terminal events were characterized by high fevers, major clotting defects, hypotension, and anuria, suggesting that the mechanism was hypersensitivity to BCG."}
{"id": "PMID:234292", "title": "Adrenal cortical carcinoma. A study of 32 patients.", "content": "Fifteen males and 17 females with adrenal cortical carcinoma were reviewed. Their average age at diagnosis was 50.33 years plus or minus 12.26 SD for males and 39.76 years plus or minus 12.02 SD for females. The 5-year survival rate in this series was 31.25%. Abdominal pain, weakness, and weight loss were the primary presenting symptoms, whereas abdominal mass, distant lymphadenopathy, hepatomegaly, and edema of the lower extremities were the main presenting signs. The major sites of distant metastatic involvement were the lungs, liver, lymph nodes, and bones. The best available mode of therapy was surgery. The use of ortho para 'DDD (o,p'DDD), either in addition to surgery or as the only mode of therapy, was not associated with any significant advantage to the patient. Female patients had a longer survival than males, probably because of their younger age at diagnosis.", "contents": "Adrenal cortical carcinoma. A study of 32 patients. Fifteen males and 17 females with adrenal cortical carcinoma were reviewed. Their average age at diagnosis was 50.33 years plus or minus 12.26 SD for males and 39.76 years plus or minus 12.02 SD for females. The 5-year survival rate in this series was 31.25%. Abdominal pain, weakness, and weight loss were the primary presenting symptoms, whereas abdominal mass, distant lymphadenopathy, hepatomegaly, and edema of the lower extremities were the main presenting signs. The major sites of distant metastatic involvement were the lungs, liver, lymph nodes, and bones. The best available mode of therapy was surgery. The use of ortho para 'DDD (o,p'DDD), either in addition to surgery or as the only mode of therapy, was not associated with any significant advantage to the patient. Female patients had a longer survival than males, probably because of their younger age at diagnosis."}
{"id": "PMID:234293", "title": "Management of recurrent melanoma of the extremity.", "content": "Two forms of therapy employed for treatment of patients with recurrent melanoma limited to the extremity, and carried out during different intervals of time, are presented. Perfusion of the involved extremity with phenylalanine mustard has resulted in a 5-year survival rate of 28% of 43 patients. A second group of 25 patients has been treated by a four-stage immunotherapy program consisting of sensitization with intradermal BCG, followed in 6 weeks by intra tumor injection of BCG. A third stage involved the activation of the patients's lymphocytes, after removal by a blood cell separator, incubated in vitro with irradiated neuraminidase-treated melanoma cells and reintroduced into the patient either by subcutaneous or intratumor injection. The fourth stage of immunotherapy involves injection of an inoculum of irradiated neuraminidase-treated autochothonous tumor cells plus BCG injected intratumorally or subcutaneously. Sixteen of 24 patients receiving immunotherapy treatment program have experienced arrest of their disease lasting from 5 to 42 months.", "contents": "Management of recurrent melanoma of the extremity. Two forms of therapy employed for treatment of patients with recurrent melanoma limited to the extremity, and carried out during different intervals of time, are presented. Perfusion of the involved extremity with phenylalanine mustard has resulted in a 5-year survival rate of 28% of 43 patients. A second group of 25 patients has been treated by a four-stage immunotherapy program consisting of sensitization with intradermal BCG, followed in 6 weeks by intra tumor injection of BCG. A third stage involved the activation of the patients's lymphocytes, after removal by a blood cell separator, incubated in vitro with irradiated neuraminidase-treated melanoma cells and reintroduced into the patient either by subcutaneous or intratumor injection. The fourth stage of immunotherapy involves injection of an inoculum of irradiated neuraminidase-treated autochothonous tumor cells plus BCG injected intratumorally or subcutaneously. Sixteen of 24 patients receiving immunotherapy treatment program have experienced arrest of their disease lasting from 5 to 42 months."}
{"id": "PMID:234294", "title": "Sequential evaluation of general immune competence in cancer patients: correlation with clinical course.", "content": "An evaluation of general immunologic reactivity was performed in 116 patients with malignant melanoma and in 40 patients with skeletal and soft tissue sarcoma who received adjunctive immunotherapy. An excellent correlation was observed between delayed cutaneous hypersensitivity to DNCB and the clinical extent of malignancy. Eighty percent of patients with Stage I disease were DNCB positive, whereas only 37% of Stage III patients were reactive on initial testing. A method for sequential evaluation of DNCB response was established, and revealed that variations in immune reactivity occurred that also correlated with the patient's clinical course. Persistence of nonreactivity to DNCB or conversion from a reactive to an anergic status was associated with postoperative recurrence in more than 80% of the patients. Conversely, conversion from an anergic to a reactive status was observed if tumor control was achieved. These results indicate that the defect in systemic immunity is closely associated with tumor cell burden, and that sequential evaluation of DNCB reactivity is a clinically useful monitor of disease progression.", "contents": "Sequential evaluation of general immune competence in cancer patients: correlation with clinical course. An evaluation of general immunologic reactivity was performed in 116 patients with malignant melanoma and in 40 patients with skeletal and soft tissue sarcoma who received adjunctive immunotherapy. An excellent correlation was observed between delayed cutaneous hypersensitivity to DNCB and the clinical extent of malignancy. Eighty percent of patients with Stage I disease were DNCB positive, whereas only 37% of Stage III patients were reactive on initial testing. A method for sequential evaluation of DNCB response was established, and revealed that variations in immune reactivity occurred that also correlated with the patient's clinical course. Persistence of nonreactivity to DNCB or conversion from a reactive to an anergic status was associated with postoperative recurrence in more than 80% of the patients. Conversely, conversion from an anergic to a reactive status was observed if tumor control was achieved. These results indicate that the defect in systemic immunity is closely associated with tumor cell burden, and that sequential evaluation of DNCB reactivity is a clinically useful monitor of disease progression."}
{"id": "PMID:234295", "title": "The immunologic and histopathologic changes of BCG-mediated tumor regression in patients with malignant melanoma.", "content": "Six patients with intradermal metastases of malignant melanoma were treated with intralesional bacile Calmette-Gu\u00e9rin (BCG). Four patients showed a good response with regression of injected, and in some cases, uninjected lesions, whereas two developed metastatic viscereal disease and died. Three of the six patients had complete regression of all lesions, and one exhibited complete regression of untreated lesions. All remain free of disease. The fourth patient had complete regression of injected and of some untreated lesions, but developed widespread dissemination and died. Preliminary experiments suggest the presence of a blocking factor in his sera which abrogates the lymphocyte stimulation in response to melanoma antigens. Three of four responders (i.e. those patients in whom treated lesions decreased in size by more than 50% for more than 1 month) showed a dramatic increase in lymphocyte stimulation to melanoma antigens. All responders (four out of four) had a marked increase to phytohemagglutinin (PHA), whereas non responders had no increase in lymphocyte stimulation either to melanoma antigens or PHA. Two of four responders showed inhibition of leukocyte migration to melanoma antigens before BCG, and two of four responders were positive after BCG. Of the nonresponders, one was positive and one negative before BCG; this remained the same after. There was a marked increase in active rosette forming cells in all responders and in one of the two nonresponders. Histopathologic studies at 3 hours, 6 hours, 24 hours, 14 days, and 4 weeks after BCG showed a definite sequence of events occurred, progressing from 1) inflammatory cell response at the periphery of the lesion, disruption of melanogenesis, extensive dumping of pigment from melanoma cells, proceeding to actual cell death at 24 hours, to 2) macrophages containing melanin and granulomas replacing tumor by 2 weeks. These studies suggest that BCG activates both specific and nonspecific immune responses. Thus, in vitro parameters of cellular immunity, including migration inhibitory factor production and inhibition of leukocyte migration, are affected by intralesional BCG, and some, particularly the lymphocyte stimulation and rosette test, seem to correlate with the clinical response of the patients.", "contents": "The immunologic and histopathologic changes of BCG-mediated tumor regression in patients with malignant melanoma. Six patients with intradermal metastases of malignant melanoma were treated with intralesional bacile Calmette-Gu\u00e9rin (BCG). Four patients showed a good response with regression of injected, and in some cases, uninjected lesions, whereas two developed metastatic viscereal disease and died. Three of the six patients had complete regression of all lesions, and one exhibited complete regression of untreated lesions. All remain free of disease. The fourth patient had complete regression of injected and of some untreated lesions, but developed widespread dissemination and died. Preliminary experiments suggest the presence of a blocking factor in his sera which abrogates the lymphocyte stimulation in response to melanoma antigens. Three of four responders (i.e. those patients in whom treated lesions decreased in size by more than 50% for more than 1 month) showed a dramatic increase in lymphocyte stimulation to melanoma antigens. All responders (four out of four) had a marked increase to phytohemagglutinin (PHA), whereas non responders had no increase in lymphocyte stimulation either to melanoma antigens or PHA. Two of four responders showed inhibition of leukocyte migration to melanoma antigens before BCG, and two of four responders were positive after BCG. Of the nonresponders, one was positive and one negative before BCG; this remained the same after. There was a marked increase in active rosette forming cells in all responders and in one of the two nonresponders. Histopathologic studies at 3 hours, 6 hours, 24 hours, 14 days, and 4 weeks after BCG showed a definite sequence of events occurred, progressing from 1) inflammatory cell response at the periphery of the lesion, disruption of melanogenesis, extensive dumping of pigment from melanoma cells, proceeding to actual cell death at 24 hours, to 2) macrophages containing melanin and granulomas replacing tumor by 2 weeks. These studies suggest that BCG activates both specific and nonspecific immune responses. Thus, in vitro parameters of cellular immunity, including migration inhibitory factor production and inhibition of leukocyte migration, are affected by intralesional BCG, and some, particularly the lymphocyte stimulation and rosette test, seem to correlate with the clinical response of the patients."}
{"id": "PMID:234296", "title": "New looks in leukemia.", "content": "Immunologic markers are now available for acute leukemia. These show that most patients now diagnosed as having acute lymphatic leukemia have blast cells which react with antihuman T antisera. In addition, about 20% of patients have blast cells which form E rosettes. These patients tend to be those with high white counts and aggressive disease. Tumor-associated antigens have been identified in acute leukemia. Antisera raised in other species by immunization appear to detect some antigens common to all acute leukemias and other antigens which can distinguish the myeloid from the lymphoid leukemias. The reactivity to leukemia antigens can be related to prognosis. The immune manipulations required to produce cure, however, are not understood. These antigenic markers, by allowing us to detect smaller amounts of tumor than can be detected by morphology alone, may help us to predict relapse and define cure.", "contents": "New looks in leukemia. Immunologic markers are now available for acute leukemia. These show that most patients now diagnosed as having acute lymphatic leukemia have blast cells which react with antihuman T antisera. In addition, about 20% of patients have blast cells which form E rosettes. These patients tend to be those with high white counts and aggressive disease. Tumor-associated antigens have been identified in acute leukemia. Antisera raised in other species by immunization appear to detect some antigens common to all acute leukemias and other antigens which can distinguish the myeloid from the lymphoid leukemias. The reactivity to leukemia antigens can be related to prognosis. The immune manipulations required to produce cure, however, are not understood. These antigenic markers, by allowing us to detect smaller amounts of tumor than can be detected by morphology alone, may help us to predict relapse and define cure."}
{"id": "PMID:234297", "title": "Purification, properties, and mode of action of hemicellulase I produced by Ceratocystis paradoxa.", "content": "A culture isolate (CP2) of the fungal plant pathogen Ceratocystis paradoxa produces at least five extra-cellular hemicellulases when grown on a medium containing a commercial hemicellulose as inducer. One of the five enzymes, hemicellulase I (HC-I), was purified by ammonium sulphate preceipitation, ion-exchange chromatography (DEAE-Sephadex and then Cellex-CM), and iso-electric focusing at pH 3-10 and 8-10. HC-I behaves as a single protein on a electrophoresis at pH 6.0 and 8.4. The enzyme degrades hemicellulose B (an arabino-4-O-methylglucurono-xylan) and arabinoxylanto arabinose, xylose, xylobiose (Xyl2; beta-D-Xylp-(1 leads to 4)-D-Xyl), and a mixture of arabinose-xylose and xylose oligosaccharides (AraXyln and Xyln, where n=3, 4, or 5). The enzyme is deduced to be an endo-enzyme. Xylotetraose (Xyl4) was the lowest homologue of the xylose oligosaccharides attacked, yielding xylobiose and xylotriose (Xyl3) only. A mechanism is postulated for this reaction. AraXyl5 were slowly hydrolysed to arabinose and the respective xylose saccharide (Xyl2-Xyl5), and thence to Xyl2 and Xyl3. Hydrolysis of the arabinofuranosyl linkage probably does not occur at the same active site as for the xylose oligosaccharides. Hemicellulose B fractions from different sources appeared to be degraded by HC-I. The enzyme showed optimum activity at pH 5.5 and 40 degrees, and Km was 4.24 mg of hemicellulose/ml.", "contents": "Purification, properties, and mode of action of hemicellulase I produced by Ceratocystis paradoxa. A culture isolate (CP2) of the fungal plant pathogen Ceratocystis paradoxa produces at least five extra-cellular hemicellulases when grown on a medium containing a commercial hemicellulose as inducer. One of the five enzymes, hemicellulase I (HC-I), was purified by ammonium sulphate preceipitation, ion-exchange chromatography (DEAE-Sephadex and then Cellex-CM), and iso-electric focusing at pH 3-10 and 8-10. HC-I behaves as a single protein on a electrophoresis at pH 6.0 and 8.4. The enzyme degrades hemicellulose B (an arabino-4-O-methylglucurono-xylan) and arabinoxylanto arabinose, xylose, xylobiose (Xyl2; beta-D-Xylp-(1 leads to 4)-D-Xyl), and a mixture of arabinose-xylose and xylose oligosaccharides (AraXyln and Xyln, where n=3, 4, or 5). The enzyme is deduced to be an endo-enzyme. Xylotetraose (Xyl4) was the lowest homologue of the xylose oligosaccharides attacked, yielding xylobiose and xylotriose (Xyl3) only. A mechanism is postulated for this reaction. AraXyl5 were slowly hydrolysed to arabinose and the respective xylose saccharide (Xyl2-Xyl5), and thence to Xyl2 and Xyl3. Hydrolysis of the arabinofuranosyl linkage probably does not occur at the same active site as for the xylose oligosaccharides. Hemicellulose B fractions from different sources appeared to be degraded by HC-I. The enzyme showed optimum activity at pH 5.5 and 40 degrees, and Km was 4.24 mg of hemicellulose/ml."}
{"id": "PMID:234302", "title": "Pulmonary edema related to changes in colloid osmotic and pulmonary artery wedge pressure in patients after acute myocardial infarction.", "content": "Pulmonary artery wedge and plasma colloid osmotic pressures and their relationship to pulmonary edema were investigated in 26 patients with acute myocardial infarction of whom 14 developed pulmonary edema. In the absence of pulmonary edema, both the pulmonary artery wedge pressure and plasma colloid osmotic pressure were in normal range; after onset pulmonary edema, a moderate increase in pulmonary wedge pressure and reduction in plasma colloid osmotic pressure were observed. When the gradient between the plasma colloid osmotic pressure and the pulmonary artery wedge pressure was calculated, highly significant differences were demonstrated (P less than 0.002). In the absence of pulmonary edema, this gradient averaged 9.7 (plus or minus 1.7 SEM) torr; following appearance of pulmonary edema, it was reduced to 1.2 (plus or minus 1.3) torr. During therapy with digoxin and furosemide, reversal of pulmonary edema was closely related to a concomitant change in the colloid osmotic-hydrostatic pressure gradient. These observations indicate that both increases in pulmonary capillary pressure and decreases in colloid osmotic pressure may follow the onset of pulmonary edema. Such decline in colloid osmotic pressure and especially the reduction in colloid osmotic-hydrostatic capillary pressure gradient may favor transudation of fluid into the lungs.", "contents": "Pulmonary edema related to changes in colloid osmotic and pulmonary artery wedge pressure in patients after acute myocardial infarction. Pulmonary artery wedge and plasma colloid osmotic pressures and their relationship to pulmonary edema were investigated in 26 patients with acute myocardial infarction of whom 14 developed pulmonary edema. In the absence of pulmonary edema, both the pulmonary artery wedge pressure and plasma colloid osmotic pressure were in normal range; after onset pulmonary edema, a moderate increase in pulmonary wedge pressure and reduction in plasma colloid osmotic pressure were observed. When the gradient between the plasma colloid osmotic pressure and the pulmonary artery wedge pressure was calculated, highly significant differences were demonstrated (P less than 0.002). In the absence of pulmonary edema, this gradient averaged 9.7 (plus or minus 1.7 SEM) torr; following appearance of pulmonary edema, it was reduced to 1.2 (plus or minus 1.3) torr. During therapy with digoxin and furosemide, reversal of pulmonary edema was closely related to a concomitant change in the colloid osmotic-hydrostatic pressure gradient. These observations indicate that both increases in pulmonary capillary pressure and decreases in colloid osmotic pressure may follow the onset of pulmonary edema. Such decline in colloid osmotic pressure and especially the reduction in colloid osmotic-hydrostatic capillary pressure gradient may favor transudation of fluid into the lungs."}
{"id": "PMID:234303", "title": "Vidicon spectrometer applied to simultaneous enzyme determinations.", "content": "Lactate dehydrogenase and alkaline phosphatase activities in the same medium can be determined simulataneously, at 350 and 550 nm, with a vidicon spectrometer. Substrate concentrations and ph have been made optimum for the combined analysis. These conditions result in activities for lactate dehydrogenase that are equivalent to those found by methods in common use, and activites for alkaline phosphatase that are about 31% below the maximum values that could be obtained with its substrate used at the same ph and temperature in the absence of NAD+ and lactate. However, activites measured by the simultaneous analysis were proportional to those obtained by other methods used in clinical laboratories, and the coefficients of variation were 2.3% for lactate dehydrogenase and 3% for alkaline phosphatase.", "contents": "Vidicon spectrometer applied to simultaneous enzyme determinations. Lactate dehydrogenase and alkaline phosphatase activities in the same medium can be determined simulataneously, at 350 and 550 nm, with a vidicon spectrometer. Substrate concentrations and ph have been made optimum for the combined analysis. These conditions result in activities for lactate dehydrogenase that are equivalent to those found by methods in common use, and activites for alkaline phosphatase that are about 31% below the maximum values that could be obtained with its substrate used at the same ph and temperature in the absence of NAD+ and lactate. However, activites measured by the simultaneous analysis were proportional to those obtained by other methods used in clinical laboratories, and the coefficients of variation were 2.3% for lactate dehydrogenase and 3% for alkaline phosphatase."}
{"id": "PMID:234304", "title": "Determination of serum thyroxine after dissociation from thyroxine-binding globulin in alkaline solution and absorption on dextran-coated charcoal.", "content": "A competitive protein-binding procedure for determining serum thyroxine is described in which thyroxine is described in which thyroxine is first dissociated from serum thyroxine-binding globulins in an alkaline solution. After binding equilibration, the unbound thyroxine is separated by dextran-coated charcoal. The procedure takes only 100 mul of serum, requires no evaporation, and is sensitive and reproducible. Results by this procedure correlate well with those for a generally accepted method.", "contents": "Determination of serum thyroxine after dissociation from thyroxine-binding globulin in alkaline solution and absorption on dextran-coated charcoal. A competitive protein-binding procedure for determining serum thyroxine is described in which thyroxine is described in which thyroxine is first dissociated from serum thyroxine-binding globulins in an alkaline solution. After binding equilibration, the unbound thyroxine is separated by dextran-coated charcoal. The procedure takes only 100 mul of serum, requires no evaporation, and is sensitive and reproducible. Results by this procedure correlate well with those for a generally accepted method."}
{"id": "PMID:234305", "title": "Evidence supporting a proposed mechanism explaining the inverse relationship between guanidinoacetate and guanidinosuccinate in human urine.", "content": "A proposed mechanism [Clin. Chem. 19, 668 (1973)] for the inverse relationship between guanidinoacetate (I) and guanidinosuccinate (II) in human urine is explored. The mechanism proposes that canavaninosuccinate (III) may be reduced to form homoserine and II or, alternatively, that the III may be acted upon by a lyase to form canavanine and fumarate. The canavanine would then proceed to transamidinate to glycine to form I. This study demonstrates for the first time that lyase activity for converting III to canavanine and fumarate exists in human liver and kidney extracts. Transamidination from canavanine to glycine to form I is also readily accomplished with human tissue. Reductive cleavage of III to II and homoserine has been demonstrated before [Clin. Chem. 15, 397 (1969)]. The optimum pH for the lyase reaction is 6.5, for the reductive cleavage it is 8.7. In following the course of the lyase reaction, we developed a technique whereby the fumarate formed was hydrated with fumarase (EC 4.2.1.2) and then dehydrogenated with malate dehydrogenase (EC 1.1.1.37). The changes in absorbance of NADH formed in the reaction were then measured and used to determine the amount of fumarate formed, as a measure of lyase activity. Canavanino-succinate lyase activity follows pseudo-first-order reaction kinetics. The Michaelis constant of this lyase was 6.16 X 10-4 mol/liter, for argininosuccinate lyase 9.74 X 10-4 mol/liter. These data suggest that the binding affinity for III to the enzyme is greater than that for argininosuccinate. Glycine added to the reaction acts as an activator, probably because it removes the canavanine from the reaction mixture. On the other hand, arginine acts as an inhibitor of III-lyase. Other substances tested, such as canavanine, fumarate, and argininosuccinate had no effect on the reaction kinetics.", "contents": "Evidence supporting a proposed mechanism explaining the inverse relationship between guanidinoacetate and guanidinosuccinate in human urine. A proposed mechanism [Clin. Chem. 19, 668 (1973)] for the inverse relationship between guanidinoacetate (I) and guanidinosuccinate (II) in human urine is explored. The mechanism proposes that canavaninosuccinate (III) may be reduced to form homoserine and II or, alternatively, that the III may be acted upon by a lyase to form canavanine and fumarate. The canavanine would then proceed to transamidinate to glycine to form I. This study demonstrates for the first time that lyase activity for converting III to canavanine and fumarate exists in human liver and kidney extracts. Transamidination from canavanine to glycine to form I is also readily accomplished with human tissue. Reductive cleavage of III to II and homoserine has been demonstrated before [Clin. Chem. 15, 397 (1969)]. The optimum pH for the lyase reaction is 6.5, for the reductive cleavage it is 8.7. In following the course of the lyase reaction, we developed a technique whereby the fumarate formed was hydrated with fumarase (EC 4.2.1.2) and then dehydrogenated with malate dehydrogenase (EC 1.1.1.37). The changes in absorbance of NADH formed in the reaction were then measured and used to determine the amount of fumarate formed, as a measure of lyase activity. Canavanino-succinate lyase activity follows pseudo-first-order reaction kinetics. The Michaelis constant of this lyase was 6.16 X 10-4 mol/liter, for argininosuccinate lyase 9.74 X 10-4 mol/liter. These data suggest that the binding affinity for III to the enzyme is greater than that for argininosuccinate. Glycine added to the reaction acts as an activator, probably because it removes the canavanine from the reaction mixture. On the other hand, arginine acts as an inhibitor of III-lyase. Other substances tested, such as canavanine, fumarate, and argininosuccinate had no effect on the reaction kinetics."}
{"id": "PMID:234306", "title": "Evidence supporting a proposed mechanism explaning the inverse relationship between guanidinoacetate and guanidinosuccinate in human urine.", "content": "A proposed mechanism [Clin. Chem. 19, 668 (1973)] for the inverse relationship beteen guanidinoacetate (I) and guanidinosuccinate (II) in human urine is explored. The mechanism proposes that canavaninosuccinate (III) may be reduced to form homoserine and II or, alternatively, that the III may be acted upon by a lyase to form canavine and fumarate. The canavanine would the proceed to transamidinate to glycine to form I. This study demonstrates for the first time that layse activity for converting III to canavanine and fumarate exists in human liver and kidney extracts. Transamidination from canavine to glycine to form I is also readily accomplised with human tissue. Reductive cleavage of III to II and homoserine has been demonstrated before [Clin. Chem. 15, 397 (1969)]. The optimum pH for the lyase reaction is 6.5, for the reductive cleavage it is 8.7. In follwing the course of the lyase reaction, we developed a technique whereby the fumarate formed was hydrated with fumarase (EC 4.2.1.2) and then dehydrogenated with malate dehydrogenase (EC. 1.1.1.37). The changes in absorbance of NADH formed in the reaction were then measured and used to determine the amount of fumarate formed, as a measure of lyase activity. Canavanino-succinate lyase activity follows pseudo-first-order reaction kinetics. The Michaelis constant of this lyase was 6.16 X 10-4 mol/liter, for argininosuccinate lyase 9.74 X 10.4 mol/liter. These data suggest that the binding afficinity for III to the enzyme is greater than that for argininosuccinate. Glycine added to the reaction acts as an activator, probably because is removes the canavanine from the reaction mixture. On the otherhand, arginine acts as an inhibitor of III-lyase. Other substances tested, such as canavaine, fumarate, and arginissuccinate had no effect on the reaction kinetics.", "contents": "Evidence supporting a proposed mechanism explaning the inverse relationship between guanidinoacetate and guanidinosuccinate in human urine. A proposed mechanism [Clin. Chem. 19, 668 (1973)] for the inverse relationship beteen guanidinoacetate (I) and guanidinosuccinate (II) in human urine is explored. The mechanism proposes that canavaninosuccinate (III) may be reduced to form homoserine and II or, alternatively, that the III may be acted upon by a lyase to form canavine and fumarate. The canavanine would the proceed to transamidinate to glycine to form I. This study demonstrates for the first time that layse activity for converting III to canavanine and fumarate exists in human liver and kidney extracts. Transamidination from canavine to glycine to form I is also readily accomplised with human tissue. Reductive cleavage of III to II and homoserine has been demonstrated before [Clin. Chem. 15, 397 (1969)]. The optimum pH for the lyase reaction is 6.5, for the reductive cleavage it is 8.7. In follwing the course of the lyase reaction, we developed a technique whereby the fumarate formed was hydrated with fumarase (EC 4.2.1.2) and then dehydrogenated with malate dehydrogenase (EC. 1.1.1.37). The changes in absorbance of NADH formed in the reaction were then measured and used to determine the amount of fumarate formed, as a measure of lyase activity. Canavanino-succinate lyase activity follows pseudo-first-order reaction kinetics. The Michaelis constant of this lyase was 6.16 X 10-4 mol/liter, for argininosuccinate lyase 9.74 X 10.4 mol/liter. These data suggest that the binding afficinity for III to the enzyme is greater than that for argininosuccinate. Glycine added to the reaction acts as an activator, probably because is removes the canavanine from the reaction mixture. On the otherhand, arginine acts as an inhibitor of III-lyase. Other substances tested, such as canavaine, fumarate, and arginissuccinate had no effect on the reaction kinetics."}
{"id": "PMID:234307", "title": "PH measurement problems affecting assay of carcinoembryonic antigen.", "content": "Measurments with combination pH electrodes of the pH of the dilute buffers used in a commercial kit (CEA-Roche) for assay of carcinoembryonic antigen resulted in pH values 0.1 to 0.3 unit lower than pH values measured on an electrode system with a capillary junction. If the pH values of these buffers were adjusted, based on such measurements, an error in the assay of 0.2 to 0.6 ng/ml in the 1.5-3.0 ng/ml range would result. We recommend that the pH of dialyzed samples and of the working ethylenediaminetetraacetate and ammonium acetate-acetic acid buffers be monitored with pH electrodes that have a capillary junction between sample and saturated KCI, as is true of most blood-pH instruments. We also recommend use of a 1 mol/liter rather than 2.5 mol/liter stock ammonium acetate-acetic acid buffer, because of the closer similarity of the pH of buffers at this molarity to those at 0.01 mol/liter.", "contents": "PH measurement problems affecting assay of carcinoembryonic antigen. Measurments with combination pH electrodes of the pH of the dilute buffers used in a commercial kit (CEA-Roche) for assay of carcinoembryonic antigen resulted in pH values 0.1 to 0.3 unit lower than pH values measured on an electrode system with a capillary junction. If the pH values of these buffers were adjusted, based on such measurements, an error in the assay of 0.2 to 0.6 ng/ml in the 1.5-3.0 ng/ml range would result. We recommend that the pH of dialyzed samples and of the working ethylenediaminetetraacetate and ammonium acetate-acetic acid buffers be monitored with pH electrodes that have a capillary junction between sample and saturated KCI, as is true of most blood-pH instruments. We also recommend use of a 1 mol/liter rather than 2.5 mol/liter stock ammonium acetate-acetic acid buffer, because of the closer similarity of the pH of buffers at this molarity to those at 0.01 mol/liter."}
{"id": "PMID:234308", "title": "Assay of L-tyrosine in serum by amperometric measurement of tyrosinase-catalyzed oxygen consumption.", "content": "A new enzymatic method for rapid direct measurement of serum tyrosine is described, based on the amperometric measurement of the rate of oxygen consumption when tyrosine is oxidized in the presence of the enzyme tyrosinase in a phosphate buffer (0.1 mol/liter, pH 7.4). A Beckman Glucose Analyzer with a Clark electrode is used for the measurement. The procedure does not require removal of serum protein, incubation nor extraction, and results are obtained in less than 1 min. Results agree closely with those obtained by a fluorometric procedure and with an amino acid analyzer.", "contents": "Assay of L-tyrosine in serum by amperometric measurement of tyrosinase-catalyzed oxygen consumption. A new enzymatic method for rapid direct measurement of serum tyrosine is described, based on the amperometric measurement of the rate of oxygen consumption when tyrosine is oxidized in the presence of the enzyme tyrosinase in a phosphate buffer (0.1 mol/liter, pH 7.4). A Beckman Glucose Analyzer with a Clark electrode is used for the measurement. The procedure does not require removal of serum protein, incubation nor extraction, and results are obtained in less than 1 min. Results agree closely with those obtained by a fluorometric procedure and with an amino acid analyzer."}
{"id": "PMID:234309", "title": "Effect of lactate dehydrogenase isoenzymes on the coupled enzymatic assay for alanine aminotransferase activity.", "content": "We show an example of the importance of specifying the form of isoenzyme and source of indicator enzymes to be used in coupled enzymatic assays. When we compared H-4 (pig heart) and M-4 (rabbit muscle) isoenzymes of lactate dehydrogenase for their suitability as indicator enzymes in the assay for alanine aminotransferase activity, we found that about fourfold as much M-4 as H-4 was required in terms of lactate dehydrogenase activity to reflect accurately equivalent amounts of alanine aminotransferase activity. Moreover, the substrate specificities of the two isoenzymes differed quantitatively.", "contents": "Effect of lactate dehydrogenase isoenzymes on the coupled enzymatic assay for alanine aminotransferase activity. We show an example of the importance of specifying the form of isoenzyme and source of indicator enzymes to be used in coupled enzymatic assays. When we compared H-4 (pig heart) and M-4 (rabbit muscle) isoenzymes of lactate dehydrogenase for their suitability as indicator enzymes in the assay for alanine aminotransferase activity, we found that about fourfold as much M-4 as H-4 was required in terms of lactate dehydrogenase activity to reflect accurately equivalent amounts of alanine aminotransferase activity. Moreover, the substrate specificities of the two isoenzymes differed quantitatively."}
{"id": "PMID:234310", "title": "Use of leuco-dyes in the quantitative colorimetric microdetermination of hemoglobin and other heme compounds.", "content": "Sensitivity, stability, and specificity of the color-producing reaction of hydrogen peroxide with bezidine, leuco-malachite green, or o-dianisidine were tested in numerous systems containing hemoglobin and other hemoproteins. Use of urea or low temperature (to minus 12 degrees C), or both, was highly beneficial, especially with leuco-malachite green, for which the color reaction was stable, after about 15 min, for longer than 24 h, with a colorless bank. Absorbance was 0.3 at a final hemoglobin concentration of 0.27 mg/liter. Nonspecific color produced by substances such as FeCl-3 and ascorbic acid was completely eliminated. Of the three leuco-dyes studied, only benzidine yielded a completely linear calibration curve, but its relative instability and reported carcinogenicity are serious disadvantages. No system tested eliminated completely the known inhibition by plasma of the peroxidase activity of these leuco dyes.", "contents": "Use of leuco-dyes in the quantitative colorimetric microdetermination of hemoglobin and other heme compounds. Sensitivity, stability, and specificity of the color-producing reaction of hydrogen peroxide with bezidine, leuco-malachite green, or o-dianisidine were tested in numerous systems containing hemoglobin and other hemoproteins. Use of urea or low temperature (to minus 12 degrees C), or both, was highly beneficial, especially with leuco-malachite green, for which the color reaction was stable, after about 15 min, for longer than 24 h, with a colorless bank. Absorbance was 0.3 at a final hemoglobin concentration of 0.27 mg/liter. Nonspecific color produced by substances such as FeCl-3 and ascorbic acid was completely eliminated. Of the three leuco-dyes studied, only benzidine yielded a completely linear calibration curve, but its relative instability and reported carcinogenicity are serious disadvantages. No system tested eliminated completely the known inhibition by plasma of the peroxidase activity of these leuco dyes."}
{"id": "PMID:234311", "title": "pH dependence of the binding of folates to milk binder in radioassay of folates.", "content": "We compare the binding of folic acid and N-5-methyltetrahydrofolic acid to milk binder in the pH range 7.4 to 10.1. At pH 7.4 the relative affinities are quite disparate, with folic acid showing the greater affinity for milk binder. As the pH is increased from 7.4 to 9.3, the difference in affinities becomes smaller, and at pH 9.3 the affinities are nearly the same. As the pH is increased from 9.3 to 10.1, the relative affinities again begin to differ, with N-5-methyltetrahydrofolic acid displaying the greater affinity. These results indicate that at a pH of 9.3 the more stable folic acid may be used as the standard in radioassay of endogenous folates.", "contents": "pH dependence of the binding of folates to milk binder in radioassay of folates. We compare the binding of folic acid and N-5-methyltetrahydrofolic acid to milk binder in the pH range 7.4 to 10.1. At pH 7.4 the relative affinities are quite disparate, with folic acid showing the greater affinity for milk binder. As the pH is increased from 7.4 to 9.3, the difference in affinities becomes smaller, and at pH 9.3 the affinities are nearly the same. As the pH is increased from 9.3 to 10.1, the relative affinities again begin to differ, with N-5-methyltetrahydrofolic acid displaying the greater affinity. These results indicate that at a pH of 9.3 the more stable folic acid may be used as the standard in radioassay of endogenous folates."}
{"id": "PMID:234316", "title": "The distribution of ammonia between extracellular and intracellular compartments of the rat brain.", "content": "1. The distribution of ammonia between extra-and intra-cellular compartments of the brain was evaluated in anaesthetized rats exposed to sustained hyperammonaemia and superimposed acute hypo- or hyper-capnia. 2. It is concluded that the concentration gradient for ammonia between arterial plasma and cerebro-spinal fluid (CSF) cannot be explained by pH-dependent non-ionic diffusion of ammonia. A continuous uptake by the brain tissue of ammonia from the CSF is postulated and possible mechanisms are discussed.", "contents": "The distribution of ammonia between extracellular and intracellular compartments of the rat brain. 1. The distribution of ammonia between extra-and intra-cellular compartments of the brain was evaluated in anaesthetized rats exposed to sustained hyperammonaemia and superimposed acute hypo- or hyper-capnia. 2. It is concluded that the concentration gradient for ammonia between arterial plasma and cerebro-spinal fluid (CSF) cannot be explained by pH-dependent non-ionic diffusion of ammonia. A continuous uptake by the brain tissue of ammonia from the CSF is postulated and possible mechanisms are discussed."}
{"id": "PMID:234317", "title": "Partial pressures of oxygen and carbon dioxide, and pH of blood sampled from wedged pulmonary artery.", "content": "1. Po2, Pco2 and pH were examined in twenty-seven pulmonary \"wedge\" samples of blood obtained from seventeen patients with various heart diseases. 2. High Po2 and pH, and low Pco2, values were found in comparison with those in simultaneous samples of peripheral arterial blood. In the pulmonary \"wedge\" samples of blood, the following mean values were found: Po2, 17.65 kPa (132.2 mmHg); Pco2, 3.10 kPa (23.2 mmHg); pH 7.47. An explanation of these findings is considered.", "contents": "Partial pressures of oxygen and carbon dioxide, and pH of blood sampled from wedged pulmonary artery. 1. Po2, Pco2 and pH were examined in twenty-seven pulmonary \"wedge\" samples of blood obtained from seventeen patients with various heart diseases. 2. High Po2 and pH, and low Pco2, values were found in comparison with those in simultaneous samples of peripheral arterial blood. In the pulmonary \"wedge\" samples of blood, the following mean values were found: Po2, 17.65 kPa (132.2 mmHg); Pco2, 3.10 kPa (23.2 mmHg); pH 7.47. An explanation of these findings is considered."}
{"id": "PMID:234360", "title": "Crosslinking and carbohydrate studies on the hydroxylated glycopeptides which accumulate in alveoli and lamellar bodies.", "content": "These data suggest that the alveolar lining layer and lamellar body membranes contain the same saline-insoluble proteins, two of which are unusual in that they contain hydroxyproline and large amounts of glycine. Neither the function nor the origin of these glycopeptides has been established, and we are currently evaluating methods of stimulating their production in animals for further study.", "contents": "Crosslinking and carbohydrate studies on the hydroxylated glycopeptides which accumulate in alveoli and lamellar bodies. These data suggest that the alveolar lining layer and lamellar body membranes contain the same saline-insoluble proteins, two of which are unusual in that they contain hydroxyproline and large amounts of glycine. Neither the function nor the origin of these glycopeptides has been established, and we are currently evaluating methods of stimulating their production in animals for further study."}
{"id": "PMID:234363", "title": "Comparison of the cardiopulmonary effects of subcutaneously administered epinephrine and terbutaline in patients with reversible airway obstruction.", "content": "The cardiopulmonary effects of epinephrine and terbutaline were compared in a doubleblind crossover study in 23 subjects with chronic obstructive airway disease. On each of three days each subject received a single subcutaneous dose of saline, 0.25 mg of epinephrine or 0.5 mg of terbutaline. Treatment with epinephrine produced significant increases in forced vital capacity (FVC), forced expiratory volume in one second (FEV-1), maximal expiratory flow rate (MEFR) and maximal mid-expiratory flow (MMEF). Terbutaline caused even more pronounced increases in all four parameters and exhibited a longer duration of action. Neither drug altered arterial pH, arterial oxygen pressure (PaO-2), or arterial carbon dioxide pressure (PaCO-2). With regard to cardiovascular effects, no alterations in either systolic or diastolic pressure were observed. Administration of epinephrine and terbutaline caused statistically significant increases in heart rate. The effect of terbutaline was more pronounced that that of epinephrine. In addition, terbutaline caused a heart rate-related depression of the T-wave of the lead 2 ECG. Neither drug altered any of the hematologic, hemochemical or urinary parameters monitored before and after treatment. Side effects were seen in eight subjects after administration of saline solution, in 13 subjects after epinephrine and in 19 subjects after terbutaline. None of these side effects was considered clinically serious and none required treatment. It is concluded from this study that subcutaneously administered terbutaline is a more effective bronchodilator than epinephrine.", "contents": "Comparison of the cardiopulmonary effects of subcutaneously administered epinephrine and terbutaline in patients with reversible airway obstruction. The cardiopulmonary effects of epinephrine and terbutaline were compared in a doubleblind crossover study in 23 subjects with chronic obstructive airway disease. On each of three days each subject received a single subcutaneous dose of saline, 0.25 mg of epinephrine or 0.5 mg of terbutaline. Treatment with epinephrine produced significant increases in forced vital capacity (FVC), forced expiratory volume in one second (FEV-1), maximal expiratory flow rate (MEFR) and maximal mid-expiratory flow (MMEF). Terbutaline caused even more pronounced increases in all four parameters and exhibited a longer duration of action. Neither drug altered arterial pH, arterial oxygen pressure (PaO-2), or arterial carbon dioxide pressure (PaCO-2). With regard to cardiovascular effects, no alterations in either systolic or diastolic pressure were observed. Administration of epinephrine and terbutaline caused statistically significant increases in heart rate. The effect of terbutaline was more pronounced that that of epinephrine. In addition, terbutaline caused a heart rate-related depression of the T-wave of the lead 2 ECG. Neither drug altered any of the hematologic, hemochemical or urinary parameters monitored before and after treatment. Side effects were seen in eight subjects after administration of saline solution, in 13 subjects after epinephrine and in 19 subjects after terbutaline. None of these side effects was considered clinically serious and none required treatment. It is concluded from this study that subcutaneously administered terbutaline is a more effective bronchodilator than epinephrine."}
{"id": "PMID:234364", "title": "Neurolept analgesia for bronchoscopic examinations.", "content": "In 38 patients requiring diagnostic bronchoscopy, three different procedures of anesthesia have been investigated. Of the three, neurolept analgesia combined with topical anesthesia of the airway proved by far the best form. It is followed by psychic indifference without lessening the patient's voluntary control, thus facilitating intricate technical manipulations on the bronchial system. No severe side effects arise when suitable equipment for diagnosing and treating respiratory and cardiovascular depression is available.", "contents": "Neurolept analgesia for bronchoscopic examinations. In 38 patients requiring diagnostic bronchoscopy, three different procedures of anesthesia have been investigated. Of the three, neurolept analgesia combined with topical anesthesia of the airway proved by far the best form. It is followed by psychic indifference without lessening the patient's voluntary control, thus facilitating intricate technical manipulations on the bronchial system. No severe side effects arise when suitable equipment for diagnosing and treating respiratory and cardiovascular depression is available."}
{"id": "PMID:234365", "title": "Evidence for pulmonary microembolization during hemodialysis.", "content": "The generation of microaggregates during the extracorporeal circulation of heparinized blood through two types of hemodialyzers was demonstrated by increased screen filtration resistance. Arterial blood deoxygenation and widening of the alveolar-arterial oxygen difference occurred following either unfiltered or inadequately filtered dialysis. These changes were consistent with pulmonary microembolization. The blood gas abnormalities and the increased screen filtration resistance were reversed or improved when venous line microemboli filters were used.", "contents": "Evidence for pulmonary microembolization during hemodialysis. The generation of microaggregates during the extracorporeal circulation of heparinized blood through two types of hemodialyzers was demonstrated by increased screen filtration resistance. Arterial blood deoxygenation and widening of the alveolar-arterial oxygen difference occurred following either unfiltered or inadequately filtered dialysis. These changes were consistent with pulmonary microembolization. The blood gas abnormalities and the increased screen filtration resistance were reversed or improved when venous line microemboli filters were used."}
{"id": "PMID:234370", "title": "[Landry-type motor polyneuropathy and spinal transection syndrome with flaccid paraplegia. Rare neurological syndromes in panarteritis nodosa].", "content": "In a 59-year-old man in complete health a pure motor polyneuropathic syndrome with quadruplegia, swallowing and respiratory paralysis developed over a few hours. A few days later he died with the clinical picture of septicaemia. In a 59-year-old woman who had been investigated and treated for a suspected carcinoma for several months a predominantly distal sensomotoric polyneuropathy syndrome developed. The further course of disease was completely misleading as regards the diagnosis due to an acutely occurring transection syndrome with flaccid paraplegia, loss of reflexes, and bladder and rectal paralysis. Due to the very unusual neurological symptoms panarteritis nodosa was only diagnosed at autopsy and by histology in both cases. Panarteritis nodosa must be considered as a differential diagnosis in Landry-type polyneuropathy as well as in an acute spinal transection syndrome. The first patient demonstrates toxic damages, the second vascular damages of the nervous system which in general determine the neurological symptomatology of this vascular disease.", "contents": "[Landry-type motor polyneuropathy and spinal transection syndrome with flaccid paraplegia. Rare neurological syndromes in panarteritis nodosa]. In a 59-year-old man in complete health a pure motor polyneuropathic syndrome with quadruplegia, swallowing and respiratory paralysis developed over a few hours. A few days later he died with the clinical picture of septicaemia. In a 59-year-old woman who had been investigated and treated for a suspected carcinoma for several months a predominantly distal sensomotoric polyneuropathy syndrome developed. The further course of disease was completely misleading as regards the diagnosis due to an acutely occurring transection syndrome with flaccid paraplegia, loss of reflexes, and bladder and rectal paralysis. Due to the very unusual neurological symptoms panarteritis nodosa was only diagnosed at autopsy and by histology in both cases. Panarteritis nodosa must be considered as a differential diagnosis in Landry-type polyneuropathy as well as in an acute spinal transection syndrome. The first patient demonstrates toxic damages, the second vascular damages of the nervous system which in general determine the neurological symptomatology of this vascular disease."}
{"id": "PMID:234372", "title": "[Antral morphology and serum-gastrin levels in achlorhydria].", "content": "38 patients were found to have achlorhydria after maximal stimulation with pentagastrin and on multiple biopsies (atrophy of gastric mucosa). It was demonstrated that the sequence pH-antroreceptors-G cells-parietal cells-pH antroreceptors was interrupted already in mild or moderately severe superficial gastritis of the antral mucosa involving more than half of the antral surface. Reduction of specific functional epithelium is unlikely in this form of inflammation so that it is probably an effect of the pH receptors.", "contents": "[Antral morphology and serum-gastrin levels in achlorhydria]. 38 patients were found to have achlorhydria after maximal stimulation with pentagastrin and on multiple biopsies (atrophy of gastric mucosa). It was demonstrated that the sequence pH-antroreceptors-G cells-parietal cells-pH antroreceptors was interrupted already in mild or moderately severe superficial gastritis of the antral mucosa involving more than half of the antral surface. Reduction of specific functional epithelium is unlikely in this form of inflammation so that it is probably an effect of the pH receptors."}
{"id": "PMID:234374", "title": "[Prenatal diagnosis of Sandhoff's disease (GM2-gangliosidosis, type 2)].", "content": "The diagnosis of GM2-gangliosidosis type 2 (Sandhoff's disease) was made prenatally (23rd week of pregnancy) by amniocentsis. A sibling with \"Tay-Sachs disease\" had died shortly before. Severe deficiency of total beta-hexosaminidase was found in amniotic fluid and amnion-cell culture. After interruption of the pregnancy the enzyme defect was also found in the fetal brain tissue and the concentration of ganglioside GM2 was three times normal, confirming the diagnosis.", "contents": "[Prenatal diagnosis of Sandhoff's disease (GM2-gangliosidosis, type 2)]. The diagnosis of GM2-gangliosidosis type 2 (Sandhoff's disease) was made prenatally (23rd week of pregnancy) by amniocentsis. A sibling with \"Tay-Sachs disease\" had died shortly before. Severe deficiency of total beta-hexosaminidase was found in amniotic fluid and amnion-cell culture. After interruption of the pregnancy the enzyme defect was also found in the fetal brain tissue and the concentration of ganglioside GM2 was three times normal, confirming the diagnosis."}
{"id": "PMID:234376", "title": "[Alpha-antitrypsin deficiency in infancy].", "content": "Clinical, histological (including electron-microscopic), immunohistochemical and genetic studies were performed on two infants with alpha1-antitrypsin deficiency. The clinical picture was one of neonatal biliary stasis. Liver biopsies revealed multiple cytoplasmic acidophilic bodies within many cells of the liver parenchyma which were strongly periodic acid-Schiff-positive, diastase-resistant and stained selectively with fluorescein-labelled rabbit antihuman alpha1-antitrypsin. Ultrastructurally, the bodies were situated within enlarged cisterns of the endoplasmatic reticulum. Both infants were of the protease inhibitor (Pi) phenotype ZZ, having inherited on PiZ gene from each parent. Results of Pi typing of both families were consistent with an autosomal co-dominant inheritance. Both infants are clinically well except for slight hepatomegaly at one year of age. But transaminase and gamma-glutamyl transpeptidase activities have remained elevated.", "contents": "[Alpha-antitrypsin deficiency in infancy]. Clinical, histological (including electron-microscopic), immunohistochemical and genetic studies were performed on two infants with alpha1-antitrypsin deficiency. The clinical picture was one of neonatal biliary stasis. Liver biopsies revealed multiple cytoplasmic acidophilic bodies within many cells of the liver parenchyma which were strongly periodic acid-Schiff-positive, diastase-resistant and stained selectively with fluorescein-labelled rabbit antihuman alpha1-antitrypsin. Ultrastructurally, the bodies were situated within enlarged cisterns of the endoplasmatic reticulum. Both infants were of the protease inhibitor (Pi) phenotype ZZ, having inherited on PiZ gene from each parent. Results of Pi typing of both families were consistent with an autosomal co-dominant inheritance. Both infants are clinically well except for slight hepatomegaly at one year of age. But transaminase and gamma-glutamyl transpeptidase activities have remained elevated."}
{"id": "PMID:234377", "title": "[Contamination of human breast milk with chlorinated hydrocarbon residues].", "content": "136 out of 137 human breast milk samples which were investigated between June 1973 and January 1974 contained remains of the insecticide DDT and its metabolite DDE, Some of them in considerable amounts. On average the quantities of DDE were double those of DDT. In 73 samples DDD could be found at the same time. DDD can be formed during metabolization of DDT. Less frequently other chlorinated hydrocarbons were found, mainly hexachlorobenzene, lindane (gamma-HCH), TECHNOLOGICAL HCH and heptachloroepoxide. On the other hand quite frequently found in animals were rarely observed. Only one of the investigated samples of human breast milk was in accordance with the recently introduced legal maximum allowed for cow's milk and milk products, It seems particularly serious that, assuming normal conditions, the ADI value for DDT in adults suggested by the WHO was exceeded on average fourfold and in the highest value 16-fold. Also noteworthy is the not infrequent contamination with polychlorinated biphenyles. These are remains of industrial products which are very similar to DDT in their toxic and physico-chemical behaviour.", "contents": "[Contamination of human breast milk with chlorinated hydrocarbon residues]. 136 out of 137 human breast milk samples which were investigated between June 1973 and January 1974 contained remains of the insecticide DDT and its metabolite DDE, Some of them in considerable amounts. On average the quantities of DDE were double those of DDT. In 73 samples DDD could be found at the same time. DDD can be formed during metabolization of DDT. Less frequently other chlorinated hydrocarbons were found, mainly hexachlorobenzene, lindane (gamma-HCH), TECHNOLOGICAL HCH and heptachloroepoxide. On the other hand quite frequently found in animals were rarely observed. Only one of the investigated samples of human breast milk was in accordance with the recently introduced legal maximum allowed for cow's milk and milk products, It seems particularly serious that, assuming normal conditions, the ADI value for DDT in adults suggested by the WHO was exceeded on average fourfold and in the highest value 16-fold. Also noteworthy is the not infrequent contamination with polychlorinated biphenyles. These are remains of industrial products which are very similar to DDT in their toxic and physico-chemical behaviour."}
{"id": "PMID:234378", "title": "[The purity of commercial insulin preparations].", "content": "Insulin preparations available in Germany were tested by polyacrylamide-disc electrophoresis. A large proportion of preparations contained proteins additional to insulin. Insulin purified chromatographically was cleaner than that by crystallization. Insulin purified by ion-exchange chromatography had the highest degree of purity: in addition to the insulin band only deamidation products of insulin were demonstrated. Deamidation occurs both in neutral and acid solvents. These observations indicate that commercial full purification of insulin is possible but not always practised.", "contents": "[The purity of commercial insulin preparations]. Insulin preparations available in Germany were tested by polyacrylamide-disc electrophoresis. A large proportion of preparations contained proteins additional to insulin. Insulin purified chromatographically was cleaner than that by crystallization. Insulin purified by ion-exchange chromatography had the highest degree of purity: in addition to the insulin band only deamidation products of insulin were demonstrated. Deamidation occurs both in neutral and acid solvents. These observations indicate that commercial full purification of insulin is possible but not always practised."}
{"id": "PMID:234379", "title": "Patterns of LH and FSH release from perifused rat pituitaries in response to infusions of hypothalamic extract.", "content": "A continuous flow incubation (perufusion) system was developed in which the secretory responses of pools of hemipituitaries from adult male rats to hypothalamic extract (HE) were characterized by serial radioimmunoassay of LH and FSH in the effluent medium. There was in initial massive release of LH and FSH which, in the absence of HE, declined to low basal levels at a rate which depended on the flow rate. Thereafter, the baseline for LH continued to decline gradually while that for FSH was stable. The rate of LH and FSH release rose abruptly after addition of the HE to the medium and returned promptly to baseline after withdrawal of the HE. During continuous infusion of HE for five hours, LH secretion was maintained at a relatively constant, elevated level. The responses to repeated identical pulses of HE were highly reproducible. The variability between responses by any one pool of tissue was significantly less than between responses of separate pituitary pools including pools comprising right and left halves of the same glands. For any given pool of pituitaries of the relationships were linear between: 1) duration of HE pulses (concentration constant) and increases in LH output, and 2) log of concentration of HE (pulse duration constant) and increases inLH and in FSH output. Consistent responses were obtained for up to 12 hr, the maximum period tested.", "contents": "Patterns of LH and FSH release from perifused rat pituitaries in response to infusions of hypothalamic extract. A continuous flow incubation (perufusion) system was developed in which the secretory responses of pools of hemipituitaries from adult male rats to hypothalamic extract (HE) were characterized by serial radioimmunoassay of LH and FSH in the effluent medium. There was in initial massive release of LH and FSH which, in the absence of HE, declined to low basal levels at a rate which depended on the flow rate. Thereafter, the baseline for LH continued to decline gradually while that for FSH was stable. The rate of LH and FSH release rose abruptly after addition of the HE to the medium and returned promptly to baseline after withdrawal of the HE. During continuous infusion of HE for five hours, LH secretion was maintained at a relatively constant, elevated level. The responses to repeated identical pulses of HE were highly reproducible. The variability between responses by any one pool of tissue was significantly less than between responses of separate pituitary pools including pools comprising right and left halves of the same glands. For any given pool of pituitaries of the relationships were linear between: 1) duration of HE pulses (concentration constant) and increases in LH output, and 2) log of concentration of HE (pulse duration constant) and increases inLH and in FSH output. Consistent responses were obtained for up to 12 hr, the maximum period tested."}
{"id": "PMID:234380", "title": "The influence of adrenergic, dopaminergic, cholinergic and serotoninergic drugs on plasma prolactin levels in ovariectomized, estrogen-treated rats.", "content": "Levels of plasma prolactin were estimated in ovariectomized, estrogen-treated rats following the systemic administration of several neural blocking and stimulating drugs. Phenoxybenzamine, an alpha-adrenergic blocker, at high doses, increased plasma prolactin. Phenotlamine, another alpha-adrenergic blocker, and propranolol, a beta-adrenergic blocker, also increased prolactin but the responses were small and transient. Clonidine, an alpha-adrenergic stimulating drug, elevated prolactin levels whereas the beta-adrenergic stimulator isoproterenol had no effect. Dopaminergic blockade by pimozide increased levels of prolactin while stimulation of dopamine receptors by apomorphine decreased prolactin release. Atropine (a muscarinic chilinergic blocker), arecoline (a muscarinic stimulator) and nicotine (a nicotinic cholinergic stimulating drug) did not affect basal prolactin levels. Mecamylamine (a nicotinic blocker) produced a small transient elevation in plasma prolactin. Methiothepin, an alleged serotoninergic blocker, markedly increased prolactin secretion, as did serotonin. The data suggested the involvement of several neurotransmitters in the control of basal secretion of prolactin.", "contents": "The influence of adrenergic, dopaminergic, cholinergic and serotoninergic drugs on plasma prolactin levels in ovariectomized, estrogen-treated rats. Levels of plasma prolactin were estimated in ovariectomized, estrogen-treated rats following the systemic administration of several neural blocking and stimulating drugs. Phenoxybenzamine, an alpha-adrenergic blocker, at high doses, increased plasma prolactin. Phenotlamine, another alpha-adrenergic blocker, and propranolol, a beta-adrenergic blocker, also increased prolactin but the responses were small and transient. Clonidine, an alpha-adrenergic stimulating drug, elevated prolactin levels whereas the beta-adrenergic stimulator isoproterenol had no effect. Dopaminergic blockade by pimozide increased levels of prolactin while stimulation of dopamine receptors by apomorphine decreased prolactin release. Atropine (a muscarinic chilinergic blocker), arecoline (a muscarinic stimulator) and nicotine (a nicotinic cholinergic stimulating drug) did not affect basal prolactin levels. Mecamylamine (a nicotinic blocker) produced a small transient elevation in plasma prolactin. Methiothepin, an alleged serotoninergic blocker, markedly increased prolactin secretion, as did serotonin. The data suggested the involvement of several neurotransmitters in the control of basal secretion of prolactin."}
{"id": "PMID:234381", "title": "Characterization and comparison of receptors for 17 beta-estradiol and progesterone in human proliferative endometrium and endometrial carcinoma.", "content": "Sedimentation coefficients of cytoplasmic estradiol and progesterone receptors of human proliferative endometrium and endometrial carcinoma were determined by sucrose gradient centrifugation. In the absence of KCl, receptors from proliferative endometrium sedimented as single bands in the 8 S region and in the presence of 0.3M KCl in the 4 S region of the gradients. Receptors from endometrial carcinoma sedimented in several bands (between 3 and 9 S). When chromatographed on agarose gel comumns, the receptors (from both normal and neoplastic tissue) showed different molecular weights in the presence and absence of KCl (approximately 40,000 and 120,000, respectively). Elution profiles from agarose gel and ion exchange columns, as well as electrophoretic patterns from isoelectric focusing, revealed a similarity between biochemical properties of the receptors from endometrial carcinoma and proliferative endometrium. While the concentration of binding sites for estradiol and progesterone in normal endometrium depended on the day of the cycle, in endometrial carcinoma it depended on the degree of differentiation of the tumor. The binding of estradiol was highest at the beginning of the proliferative phase and declined continuously towards the 14th day of the cycle. In contrast, the concentration of progesterone binding sites was relatively low throughout the proliferative phase. In endometrial carcinoma low binding of estradiol was obtained in well differentiated tumors and high binding (as high as in proliferative endometrium) in undifferentiated tumors. For progesterone the contrary was the case. There was no difference in pH sensitivity between cytoplasmic receptors from normal and neoplastic tissue, optimal binding occurring at pH 7. Dissociation constants (Kd) for estradiol and progesterone depended on the degree of tumor differentiation. Kd values increased for E2 and decreased for P with increasing differentiation of the tumor. Competition studies with various unlabeled steroids revealed no significant difference between the specificity of the receptors from proliverative and neoplastic endometrium.", "contents": "Characterization and comparison of receptors for 17 beta-estradiol and progesterone in human proliferative endometrium and endometrial carcinoma. Sedimentation coefficients of cytoplasmic estradiol and progesterone receptors of human proliferative endometrium and endometrial carcinoma were determined by sucrose gradient centrifugation. In the absence of KCl, receptors from proliferative endometrium sedimented as single bands in the 8 S region and in the presence of 0.3M KCl in the 4 S region of the gradients. Receptors from endometrial carcinoma sedimented in several bands (between 3 and 9 S). When chromatographed on agarose gel comumns, the receptors (from both normal and neoplastic tissue) showed different molecular weights in the presence and absence of KCl (approximately 40,000 and 120,000, respectively). Elution profiles from agarose gel and ion exchange columns, as well as electrophoretic patterns from isoelectric focusing, revealed a similarity between biochemical properties of the receptors from endometrial carcinoma and proliferative endometrium. While the concentration of binding sites for estradiol and progesterone in normal endometrium depended on the day of the cycle, in endometrial carcinoma it depended on the degree of differentiation of the tumor. The binding of estradiol was highest at the beginning of the proliferative phase and declined continuously towards the 14th day of the cycle. In contrast, the concentration of progesterone binding sites was relatively low throughout the proliferative phase. In endometrial carcinoma low binding of estradiol was obtained in well differentiated tumors and high binding (as high as in proliferative endometrium) in undifferentiated tumors. For progesterone the contrary was the case. There was no difference in pH sensitivity between cytoplasmic receptors from normal and neoplastic tissue, optimal binding occurring at pH 7. Dissociation constants (Kd) for estradiol and progesterone depended on the degree of tumor differentiation. Kd values increased for E2 and decreased for P with increasing differentiation of the tumor. Competition studies with various unlabeled steroids revealed no significant difference between the specificity of the receptors from proliverative and neoplastic endometrium."}
{"id": "PMID:234382", "title": "Cyclic nucleotide phosphodiesterase from bone: characterization of the enzyme and studies of inhibition by thyroid hormones.", "content": "Studies were carried out to characterize the cyclic nucleotide phosphodiesterase from rat calvaria. 25-40% of the total enzyme activity was membrane-bound. pH, magnesium, and temperature requirements conformed closely to those established for phosphodiesterase from other tissues. Kinetic evidence was found for dual enzyme activities with different substrate affinities for both the particulate and soluble enzyme. Apparent Kms for the soluble enzyme (3.5 times 10-6 and 2.5 times 10-5M) approximated those for the particulate enzyme (5.7 times 10-6 and 2.5 times 10-5M). L-Thyroxine, 10-5M, inhibited competitively the low- and high-Km enzymes from both the particulate and soluble fractions (Ki equals 1.7 times 10-5M). T4 was more potent an inhibitor than T3 with all enzyme fractions, but this relationship could be altered by adding protein to the incubation mixtures. Tests of diverse thyroid hormone analogues showed that 1) T4 and its derivatives were more potent than T3 and its analogues; 2) acetic and propionic acid derivatives were more potent than the thyronines; 3) \"reverse T3,\" an antagonist of some T3 actions, also inhibited phosphodiesterase. These effects were not attributable to chelation, and were not duplicated by iodide or by other physiologically inactive thyroid hormone analogues.", "contents": "Cyclic nucleotide phosphodiesterase from bone: characterization of the enzyme and studies of inhibition by thyroid hormones. Studies were carried out to characterize the cyclic nucleotide phosphodiesterase from rat calvaria. 25-40% of the total enzyme activity was membrane-bound. pH, magnesium, and temperature requirements conformed closely to those established for phosphodiesterase from other tissues. Kinetic evidence was found for dual enzyme activities with different substrate affinities for both the particulate and soluble enzyme. Apparent Kms for the soluble enzyme (3.5 times 10-6 and 2.5 times 10-5M) approximated those for the particulate enzyme (5.7 times 10-6 and 2.5 times 10-5M). L-Thyroxine, 10-5M, inhibited competitively the low- and high-Km enzymes from both the particulate and soluble fractions (Ki equals 1.7 times 10-5M). T4 was more potent an inhibitor than T3 with all enzyme fractions, but this relationship could be altered by adding protein to the incubation mixtures. Tests of diverse thyroid hormone analogues showed that 1) T4 and its derivatives were more potent than T3 and its analogues; 2) acetic and propionic acid derivatives were more potent than the thyronines; 3) \"reverse T3,\" an antagonist of some T3 actions, also inhibited phosphodiesterase. These effects were not attributable to chelation, and were not duplicated by iodide or by other physiologically inactive thyroid hormone analogues."}
{"id": "PMID:234383", "title": "Pathway from progesterone to 5alpha-reduced c19 steroids not involving androstenedione and testosterone in immature mouse testes in vitro.", "content": "Testicular homogenates from mice of 23 and 70 days of age were incubated for 3-120 min with either 3-H-progesterone, 14-C-progesterone, 3-H-5alpha-pregnane-3,20-dione or 14-C-progesterone plus 3H-5alpha-pregnane-3,20-dione in the presence of NADPH. After incubation, radioactive products were purified and identified by column and paper chromatography, with derivative formation and recrystallization to constant specific activity. In immature mouse testes, the results indicate two biosynthetic pathways leading to C19 steroids from progesterone, one from progesterone via 17-hydroxyprogesterone and androstenedione to testosterone and a second via 5alpha-reduced C21 steroids to 5alpha-reduced C19 steroids such as androsterone and 5alpha-androstane-3alpha,17beta-diol. In adult mouse testes, very few 5alpha-reduced metabolites of all the delta-4-3-ketosteroids are shown to be produced from progesterone, while evident 17alpha-hydroxylation of 5alpha-pregnane-3,20-dione followed by C17-20 lyase reaction is demonstrated.", "contents": "Pathway from progesterone to 5alpha-reduced c19 steroids not involving androstenedione and testosterone in immature mouse testes in vitro. Testicular homogenates from mice of 23 and 70 days of age were incubated for 3-120 min with either 3-H-progesterone, 14-C-progesterone, 3-H-5alpha-pregnane-3,20-dione or 14-C-progesterone plus 3H-5alpha-pregnane-3,20-dione in the presence of NADPH. After incubation, radioactive products were purified and identified by column and paper chromatography, with derivative formation and recrystallization to constant specific activity. In immature mouse testes, the results indicate two biosynthetic pathways leading to C19 steroids from progesterone, one from progesterone via 17-hydroxyprogesterone and androstenedione to testosterone and a second via 5alpha-reduced C21 steroids to 5alpha-reduced C19 steroids such as androsterone and 5alpha-androstane-3alpha,17beta-diol. In adult mouse testes, very few 5alpha-reduced metabolites of all the delta-4-3-ketosteroids are shown to be produced from progesterone, while evident 17alpha-hydroxylation of 5alpha-pregnane-3,20-dione followed by C17-20 lyase reaction is demonstrated."}
{"id": "PMID:234384", "title": "Temperature-determined enzymatic functions in octopine dehydrogenase.", "content": "We investigated the temperature dependence of several functions of octopine dehydrogenase, a monomeric enzyme extracted from the shell fish Pecten maximus L. We found that six enzymatic functions are temperature independent or change only negligibly with temperatue. These are the dissociation constants of three coenzyme complexes and the Michaelis Km values for NAD, NADH and one of the substrates (D-octopine). This is taken as an indication of a temperature-regulatory mechanism which enables the enzyme to maintain a constant level of NAD, NADH and D-octopine in binary and ternary complexes independent of fluctuations of the external temperature. This is discussed with reference to enzymes from other poikilotherms, which reportedly display similar biologically meaningful response to temperature. We also discuss the meaning of our data from a thermodynamic viewpoint. Considering that in a temperature-independent binding process only entropy changes contribute to the standard free-energy change, we speculate on possible molecular models which might account for our results. We also investigate the activation-energy parameters for the reaction catalyzed by octopine dehydrogenase, as obtained from the temperature dependence of V. It is found that octopine dehydrogenase, relative to other dehydrogenases, is provided with a rather low delta H not equal to, which enables the enzyme to change its turnover number by only a small factor in the temperature range 5--35 degrees C.", "contents": "Temperature-determined enzymatic functions in octopine dehydrogenase. We investigated the temperature dependence of several functions of octopine dehydrogenase, a monomeric enzyme extracted from the shell fish Pecten maximus L. We found that six enzymatic functions are temperature independent or change only negligibly with temperatue. These are the dissociation constants of three coenzyme complexes and the Michaelis Km values for NAD, NADH and one of the substrates (D-octopine). This is taken as an indication of a temperature-regulatory mechanism which enables the enzyme to maintain a constant level of NAD, NADH and D-octopine in binary and ternary complexes independent of fluctuations of the external temperature. This is discussed with reference to enzymes from other poikilotherms, which reportedly display similar biologically meaningful response to temperature. We also discuss the meaning of our data from a thermodynamic viewpoint. Considering that in a temperature-independent binding process only entropy changes contribute to the standard free-energy change, we speculate on possible molecular models which might account for our results. We also investigate the activation-energy parameters for the reaction catalyzed by octopine dehydrogenase, as obtained from the temperature dependence of V. It is found that octopine dehydrogenase, relative to other dehydrogenases, is provided with a rather low delta H not equal to, which enables the enzyme to change its turnover number by only a small factor in the temperature range 5--35 degrees C."}
{"id": "PMID:234385", "title": "Lipid peroxidation in isolated hepatocytes.", "content": "Intracellular lipid peroxidation was initiated by the addition of ADP-complexed ferric iron to isolated rat hepatocytes and the reaction monitored by the thiobarbituric acid method or by measurement of the formation of conjugated dienes. Both the production of malondialdehyde (thiobarbituric-acid-reacting substances) and of conjugated dienes was dependent, on the ADP-Fe-3+ concentration in a dose-related fashion. Malondialdehyde formation stopped spontaneously within 20 min after the initiation of the reaction and the plateau reached was also related to the ADP-Fe-3+ concentration. Control experiments revealed that more than 90% of the malondialdehyde accumulating during the incubation period could be ascribed to intracellular production. The cellular NADPH/NADP+ ratio was always high and only slightly decreased upon ADP-Fe-3+-induced lipid peroxidation which, however, was associated with a marked decrease in the cellular glutathione concentration. The rate of accumulation of malondialdehyde as well as the final level reached during ADP-Fe-3+-initiated lipid peroxidation was increased by the addition of chloral hydrate. This apparent stimulatory effect could, however, be ascribed to the inhibition of the mitochondrial oxidation of the malondialdehyde formed during cellular lipid peroxidation, thus allowing more malondialdehyde to accumulate during the process. ADP-Fe-3+-induced cellular lipid peroxidation was associated with a decrease in the concentration of glutathione. Also, lowering of the intracellular glutathione level by the addition of diethyl maleate or by simply preincubating the hepatocytes (up to 50 min) promoted the ADP-Fe-3+ malondialdehyde production and formation of conjugated dienes. Furthermore, when cellular glutathione concentration had been lowered by preincubation of the hepatocytes, significant malondialdehyde production could be observed even at ADP-Fe-3+ concentrations which were too low to induce measurable lipid peroxidation in fresh hepatocytes. It is thus concluded that glutathione has an important role in the cell defence against lipid peroxidation and suggested that the isolated hepatocytes provide a suitable experimental model system for the characterization of this and other possible cellular defence mechanisms and how they are affected by the nutritional status of the donor animal.", "contents": "Lipid peroxidation in isolated hepatocytes. Intracellular lipid peroxidation was initiated by the addition of ADP-complexed ferric iron to isolated rat hepatocytes and the reaction monitored by the thiobarbituric acid method or by measurement of the formation of conjugated dienes. Both the production of malondialdehyde (thiobarbituric-acid-reacting substances) and of conjugated dienes was dependent, on the ADP-Fe-3+ concentration in a dose-related fashion. Malondialdehyde formation stopped spontaneously within 20 min after the initiation of the reaction and the plateau reached was also related to the ADP-Fe-3+ concentration. Control experiments revealed that more than 90% of the malondialdehyde accumulating during the incubation period could be ascribed to intracellular production. The cellular NADPH/NADP+ ratio was always high and only slightly decreased upon ADP-Fe-3+-induced lipid peroxidation which, however, was associated with a marked decrease in the cellular glutathione concentration. The rate of accumulation of malondialdehyde as well as the final level reached during ADP-Fe-3+-initiated lipid peroxidation was increased by the addition of chloral hydrate. This apparent stimulatory effect could, however, be ascribed to the inhibition of the mitochondrial oxidation of the malondialdehyde formed during cellular lipid peroxidation, thus allowing more malondialdehyde to accumulate during the process. ADP-Fe-3+-induced cellular lipid peroxidation was associated with a decrease in the concentration of glutathione. Also, lowering of the intracellular glutathione level by the addition of diethyl maleate or by simply preincubating the hepatocytes (up to 50 min) promoted the ADP-Fe-3+ malondialdehyde production and formation of conjugated dienes. Furthermore, when cellular glutathione concentration had been lowered by preincubation of the hepatocytes, significant malondialdehyde production could be observed even at ADP-Fe-3+ concentrations which were too low to induce measurable lipid peroxidation in fresh hepatocytes. It is thus concluded that glutathione has an important role in the cell defence against lipid peroxidation and suggested that the isolated hepatocytes provide a suitable experimental model system for the characterization of this and other possible cellular defence mechanisms and how they are affected by the nutritional status of the donor animal."}
{"id": "PMID:234407", "title": "Hyporeactivity to interferon induction: characterization of a hyporeactive factor in the serum of encephalomyocarditis virus-infected mice.", "content": "Mice infected with encephalomyocarditis virus develop a severe state of hyporeactivity to interferon induction. One mechanisms possibly responsibile for development of hyporesponsiveness in these animals is a circulating factor which can be detected in their serum 96 h after encephalomyocarditis virus infection (at the time of peak hyporeactivity in vivo). This report describes some of the physiocochemical characteristics of this serum hyporeactive factor (SHF). SHF is a protein with a molecular weight between 20,000 and 40,000 that was extremely labile at 56 C, losing greater than 90% of its biological activity in 8 min, but stable at 37 c for at least 4 h. Hyporeactive factor was also stable over a pH range of 2 to 11 for 48 h at 4 C. These results suggest that SHF is physicochemically similar to interferon. However, no interferon could be detected in the SHF preparation, and no loss in biological activity was observed when the serum factor was incubated with anti-interferon antibody, suggesting that they are separate substances.", "contents": "Hyporeactivity to interferon induction: characterization of a hyporeactive factor in the serum of encephalomyocarditis virus-infected mice. Mice infected with encephalomyocarditis virus develop a severe state of hyporeactivity to interferon induction. One mechanisms possibly responsibile for development of hyporesponsiveness in these animals is a circulating factor which can be detected in their serum 96 h after encephalomyocarditis virus infection (at the time of peak hyporeactivity in vivo). This report describes some of the physiocochemical characteristics of this serum hyporeactive factor (SHF). SHF is a protein with a molecular weight between 20,000 and 40,000 that was extremely labile at 56 C, losing greater than 90% of its biological activity in 8 min, but stable at 37 c for at least 4 h. Hyporeactive factor was also stable over a pH range of 2 to 11 for 48 h at 4 C. These results suggest that SHF is physicochemically similar to interferon. However, no interferon could be detected in the SHF preparation, and no loss in biological activity was observed when the serum factor was incubated with anti-interferon antibody, suggesting that they are separate substances."}
{"id": "PMID:234408", "title": "Effect of gold on the immune response of mice.", "content": "Separate concurrent injection of organic gold compounds and antigen into mice resulted in immunoenhancement that could be measured by direct and indirect plaque-forming cells, rosette-forming cells, and serum antibody assays. Kinetics of the immune response showed variable effects through day 9 of the experiment. Studies with British anti-lewisite, a gold antagonist, showed that the gold must stay in the system 1 day to obtain immunoenhancement.", "contents": "Effect of gold on the immune response of mice. Separate concurrent injection of organic gold compounds and antigen into mice resulted in immunoenhancement that could be measured by direct and indirect plaque-forming cells, rosette-forming cells, and serum antibody assays. Kinetics of the immune response showed variable effects through day 9 of the experiment. Studies with British anti-lewisite, a gold antagonist, showed that the gold must stay in the system 1 day to obtain immunoenhancement."}
{"id": "PMID:234409", "title": "Studies on the differentiation of retinal pigmented epithelium cells in culture.", "content": "Sephadex G-25 fractions of chick embryo extract affect the differentiation of cloned embryonic pigmented epithelial cells (PE) in culture. Both tyrosinase activity and amounts of melanin are markedly affected by the extract fractions. 5-Hydroxyindole decreased melanin accumulation in PE cells while alpha-methyl-p-tyrosine had no apparent effect on the process. Melanin disposal as well as biosynthesis may be important in controlling the accumulation of pigment in PE cells under culture conditions. Triiodothyronine greatly increased visible pigmentation and affected the morphology of cultured PE cells.", "contents": "Studies on the differentiation of retinal pigmented epithelium cells in culture. Sephadex G-25 fractions of chick embryo extract affect the differentiation of cloned embryonic pigmented epithelial cells (PE) in culture. Both tyrosinase activity and amounts of melanin are markedly affected by the extract fractions. 5-Hydroxyindole decreased melanin accumulation in PE cells while alpha-methyl-p-tyrosine had no apparent effect on the process. Melanin disposal as well as biosynthesis may be important in controlling the accumulation of pigment in PE cells under culture conditions. Triiodothyronine greatly increased visible pigmentation and affected the morphology of cultured PE cells."}
{"id": "PMID:234410", "title": "Effects of monosodium glutamate on chick embryo retina in culture.", "content": "Monosodium glutamate added to 12-day chick embryo retinas in culture causes severe morphologic damage to the retina as judged by light microscopic examination. Damage is evident after a few hours with concentrations as low as 0.3 mM. Glutamyltransferase induction is also appreciably inhibited by the amino acid. General protein synthesis and RNA synthesis appear to be less affected.", "contents": "Effects of monosodium glutamate on chick embryo retina in culture. Monosodium glutamate added to 12-day chick embryo retinas in culture causes severe morphologic damage to the retina as judged by light microscopic examination. Damage is evident after a few hours with concentrations as low as 0.3 mM. Glutamyltransferase induction is also appreciably inhibited by the amino acid. General protein synthesis and RNA synthesis appear to be less affected."}
{"id": "PMID:234411", "title": "Differential effects of inhibitors of monoamine oxidase Types A and B on the adrenergic system of the rabbit iris.", "content": "Topical instillation of inhibitors of monoamine oxidase Types A and B into the rabbit eye, followed by the administration of a releaser of monoamines (Ro 4-1284), induces strong and sustained dilation of the iris. The mydriatic pattern differs markedly with A- and B-inhibitors and with the duration of the inhibitor treatment. The Type B inhibitor, deprenyl, prevents the degradation of exogenous 2-phenylethylamine and possibly of the endogenous amine X capable of releasing monoamines from a compartment less accessible to Ro-1284.", "contents": "Differential effects of inhibitors of monoamine oxidase Types A and B on the adrenergic system of the rabbit iris. Topical instillation of inhibitors of monoamine oxidase Types A and B into the rabbit eye, followed by the administration of a releaser of monoamines (Ro 4-1284), induces strong and sustained dilation of the iris. The mydriatic pattern differs markedly with A- and B-inhibitors and with the duration of the inhibitor treatment. The Type B inhibitor, deprenyl, prevents the degradation of exogenous 2-phenylethylamine and possibly of the endogenous amine X capable of releasing monoamines from a compartment less accessible to Ro-1284."}
{"id": "PMID:234412", "title": "The effect of intraocular ablation of the pecten oculi of the chicken.", "content": "The pecten oculi of 20 chickens was unilaterally ablated by intraocular electrocautery. Although the pecten was totally destroyed in 13 of the 20 birds, the retina remained histologically normal. All of the birds sustaining total lesion of the pecten retained the pupillary reflex and could peck up food and avoid objects when the control eye was covered. The intraocular pH of 5 operated birds was measured in vivo and averaged 7.35 (range 7.40 to 7.33) in operated eyes and 7.56 (range 7.65 to 7.50) in control eyes. It is suggested that the function of the pecten is not primarily nutritive and may instead be related to intraocular pH regulation.", "contents": "The effect of intraocular ablation of the pecten oculi of the chicken. The pecten oculi of 20 chickens was unilaterally ablated by intraocular electrocautery. Although the pecten was totally destroyed in 13 of the 20 birds, the retina remained histologically normal. All of the birds sustaining total lesion of the pecten retained the pupillary reflex and could peck up food and avoid objects when the control eye was covered. The intraocular pH of 5 operated birds was measured in vivo and averaged 7.35 (range 7.40 to 7.33) in operated eyes and 7.56 (range 7.65 to 7.50) in control eyes. It is suggested that the function of the pecten is not primarily nutritive and may instead be related to intraocular pH regulation."}
{"id": "PMID:234414", "title": "Stability studies with amphotericin B and amphotericin B methyl ester.", "content": "In solid form, amphotericin B and amphotericin B methyl ester free base exhibit similar stability. Acid salts of the methyl ester derivative stored under identical conditions are less stable. In solution, amphotericin B is generally more stable than its methy ester salts. However, when pH is adjusted to 6.0 and storage temperature held at 5 degrees C the methyl ester salts reflect the stability exhibited by the parent compound, amphotericin B.", "contents": "Stability studies with amphotericin B and amphotericin B methyl ester. In solid form, amphotericin B and amphotericin B methyl ester free base exhibit similar stability. Acid salts of the methyl ester derivative stored under identical conditions are less stable. In solution, amphotericin B is generally more stable than its methy ester salts. However, when pH is adjusted to 6.0 and storage temperature held at 5 degrees C the methyl ester salts reflect the stability exhibited by the parent compound, amphotericin B."}
{"id": "PMID:234415", "title": "In vitro activity of sisomicin, an aminoglycoside antibiotic, against clinical isolates.", "content": "Sisomicin, a new aminoglycoside antibiotic which is produced by Micromonospora myoensis, was studied against 565 clinical isolates of gram-negative bacilli and gram-positive cocci. With the exception of Serratia marcescens, over 90% of isolates of gram-negative bacilli were inhibited by 1.56 mug/ml or less of sisomicin. Sisomicin was slightly more active than gentamicin and tobramycin aganist isolates of Escherichia coli, Proteus mirabilis and Klebsiella spp. It was substantially more active than butirosin and kanamycin against all gram-negative bacilli. Isolates of gram-negative bacilli which were resistant to gentamicin and tobramycin were also resistant to sisomicin. Most of these isolates were sensitive to amikacin.", "contents": "In vitro activity of sisomicin, an aminoglycoside antibiotic, against clinical isolates. Sisomicin, a new aminoglycoside antibiotic which is produced by Micromonospora myoensis, was studied against 565 clinical isolates of gram-negative bacilli and gram-positive cocci. With the exception of Serratia marcescens, over 90% of isolates of gram-negative bacilli were inhibited by 1.56 mug/ml or less of sisomicin. Sisomicin was slightly more active than gentamicin and tobramycin aganist isolates of Escherichia coli, Proteus mirabilis and Klebsiella spp. It was substantially more active than butirosin and kanamycin against all gram-negative bacilli. Isolates of gram-negative bacilli which were resistant to gentamicin and tobramycin were also resistant to sisomicin. Most of these isolates were sensitive to amikacin."}
{"id": "PMID:234416", "title": "Assay of deoxyribonucleic acid homology using a single-strand-specific nuclease at 75 C.", "content": "We investigated the conditions under which a crude preparation of endonuclease S1 gives maximal hydrolysis of denatured deoxyribonucleic acid (DNA) while giving minimal hydrolysis of native DNA. The hydrolysis was measured by filtering and determining the acid-insoluble reaction product using 3H-labeled substrates. We also investigated various parameters in making this measurement. Under appropriate conditions (in 1 mM ZnSO-4, 0.168 M NaCl at pH 4.8) denatured DNA is hydrolyzed within 3% of completion whereas native DNA is essentially unaffected. The reaction was applied to assay plasmid DNA homoand heteroduplexes for which the method proves to be simple, fast, and reproducible.", "contents": "Assay of deoxyribonucleic acid homology using a single-strand-specific nuclease at 75 C. We investigated the conditions under which a crude preparation of endonuclease S1 gives maximal hydrolysis of denatured deoxyribonucleic acid (DNA) while giving minimal hydrolysis of native DNA. The hydrolysis was measured by filtering and determining the acid-insoluble reaction product using 3H-labeled substrates. We also investigated various parameters in making this measurement. Under appropriate conditions (in 1 mM ZnSO-4, 0.168 M NaCl at pH 4.8) denatured DNA is hydrolyzed within 3% of completion whereas native DNA is essentially unaffected. The reaction was applied to assay plasmid DNA homoand heteroduplexes for which the method proves to be simple, fast, and reproducible."}
{"id": "PMID:234417", "title": "Isolation of super-repressor mutants in the histidine utilization system of Salmonella typhimurium.", "content": "Two super-repressor mutations in the histidine utilization (hut) operons of Salmonella typhimurium are described. Cells bearing either of these mutations have levels of hut enzymes that do not increase above the uninduced levels when growth is in the presence of either histidine or the gratuitous inducer imidazole propionate. Both mutations lie in the region of the gene for the hut repressor, hutC, and reverse mutations of both are to the constitutive (repressor-negative) rather than to the inducible (wild type) phenotype. In hybrid merodiploid strains the super-repressor mutations are dominant over either wild-type (hutC+) or repressor-negative (hutC-) alleles. Whereas both super-repressor mutations cause the uninducible synthesis of hut enzymes, the degree of repression is different. One mutation causes repression of enzyme synthesis in one of the two hut operons to a level below the basal, uninduced level of wild-type cells. The other mutation causes repression to a lesser degree than in wild-type cells, so that the hut enzymes are present at a level above the normal basal level; this partially constitutive synthesis is greater for the enzymes of one of the hut operons than for the enzymes of the other. Thus, both mutations apparently result in repressors with altered operator-binding properties, in addition to altered inducer-binding properties.", "contents": "Isolation of super-repressor mutants in the histidine utilization system of Salmonella typhimurium. Two super-repressor mutations in the histidine utilization (hut) operons of Salmonella typhimurium are described. Cells bearing either of these mutations have levels of hut enzymes that do not increase above the uninduced levels when growth is in the presence of either histidine or the gratuitous inducer imidazole propionate. Both mutations lie in the region of the gene for the hut repressor, hutC, and reverse mutations of both are to the constitutive (repressor-negative) rather than to the inducible (wild type) phenotype. In hybrid merodiploid strains the super-repressor mutations are dominant over either wild-type (hutC+) or repressor-negative (hutC-) alleles. Whereas both super-repressor mutations cause the uninducible synthesis of hut enzymes, the degree of repression is different. One mutation causes repression of enzyme synthesis in one of the two hut operons to a level below the basal, uninduced level of wild-type cells. The other mutation causes repression to a lesser degree than in wild-type cells, so that the hut enzymes are present at a level above the normal basal level; this partially constitutive synthesis is greater for the enzymes of one of the hut operons than for the enzymes of the other. Thus, both mutations apparently result in repressors with altered operator-binding properties, in addition to altered inducer-binding properties."}
{"id": "PMID:234418", "title": "Production of racemic lactic acid in Pediococcus cerevisiae cultures by two lactate dehydrogenases.", "content": "Nicotinamide adenine dinucleotide (NAD)-dependent d(minus)-and l(plus)-lactate dehydrogenases have been partially purified 89- and 70-fold simultaneously from cell-free extracts of Pediococcus cerevisiae. Native molecular weights, as estimated from molecular sieve chromatography and electrophoresis in nondenaturing polyacrylamide gels, are 71,000 to 73,000 for d(minus)-lactate dehydrogenase and 136,000 to 139,000 for l(plus)-lactate dehydrogenase. Electrophoresis in sodium dodecyl sulfate-containing gels reveals subunits with approximate molecular weights of 37,000 to 39,000 for both enzymes. By lowering the pyruvate concentration from 5.0 to 0.5 mM, the pH optimum for pyruvate reduction by d(minus)-lactate dehydrogenase decreases from pH 8.0 to 3.6. However, l(plus)-lactate dehydrogenase displays an optimum for pyruvate reduction between pH 4.5 and 6.0 regardless of the pyruvate concentration. The enzymes obey Michaelis-Menten kinetics for both pyruvate and reduced NAD at pH 5.4 and 7.4, with increased affinity for both substrates at the acid pH. alpha-Ketobutyrate can be used as a reducible substrate, whereas oxamate has no inhibitory effect on lactate oxidation by either enzyme. Adenosine triphosphate causes inhibition of both enzymes by competition with reduced NAD. Adenosine diphosphate is also inhibitory under the same conditions, whereas NAD acts as a product inhibitor. These results are discussed with relation to the lactate isomer production during the growth cycle of P. cerevisiae.", "contents": "Production of racemic lactic acid in Pediococcus cerevisiae cultures by two lactate dehydrogenases. Nicotinamide adenine dinucleotide (NAD)-dependent d(minus)-and l(plus)-lactate dehydrogenases have been partially purified 89- and 70-fold simultaneously from cell-free extracts of Pediococcus cerevisiae. Native molecular weights, as estimated from molecular sieve chromatography and electrophoresis in nondenaturing polyacrylamide gels, are 71,000 to 73,000 for d(minus)-lactate dehydrogenase and 136,000 to 139,000 for l(plus)-lactate dehydrogenase. Electrophoresis in sodium dodecyl sulfate-containing gels reveals subunits with approximate molecular weights of 37,000 to 39,000 for both enzymes. By lowering the pyruvate concentration from 5.0 to 0.5 mM, the pH optimum for pyruvate reduction by d(minus)-lactate dehydrogenase decreases from pH 8.0 to 3.6. However, l(plus)-lactate dehydrogenase displays an optimum for pyruvate reduction between pH 4.5 and 6.0 regardless of the pyruvate concentration. The enzymes obey Michaelis-Menten kinetics for both pyruvate and reduced NAD at pH 5.4 and 7.4, with increased affinity for both substrates at the acid pH. alpha-Ketobutyrate can be used as a reducible substrate, whereas oxamate has no inhibitory effect on lactate oxidation by either enzyme. Adenosine triphosphate causes inhibition of both enzymes by competition with reduced NAD. Adenosine diphosphate is also inhibitory under the same conditions, whereas NAD acts as a product inhibitor. These results are discussed with relation to the lactate isomer production during the growth cycle of P. cerevisiae."}
{"id": "PMID:234419", "title": "Marker discrimination in deoxyribonucleic acid-mediated transformation of various Pneumococcus strains.", "content": "The function responsible for discrimination among markers (point mutations) in Pneumococcus (hex) was traced back to the early strains used to demonstrate the chemical basis of transformation in the early 1940s. Those currently used laboratory strains failing to manifest this function arose from a single subline of the original strain. The function was also evident in other independently isolated strains including a number of different serological types. The hex function was not evident in transformation between heterologous pneumococcal strains probably as a result of the sensitivity of the function to saturation in the presence of deoxyribonucleic acid from closely related but nonisogenic strains.", "contents": "Marker discrimination in deoxyribonucleic acid-mediated transformation of various Pneumococcus strains. The function responsible for discrimination among markers (point mutations) in Pneumococcus (hex) was traced back to the early strains used to demonstrate the chemical basis of transformation in the early 1940s. Those currently used laboratory strains failing to manifest this function arose from a single subline of the original strain. The function was also evident in other independently isolated strains including a number of different serological types. The hex function was not evident in transformation between heterologous pneumococcal strains probably as a result of the sensitivity of the function to saturation in the presence of deoxyribonucleic acid from closely related but nonisogenic strains."}
{"id": "PMID:234420", "title": "Changes in composition, biosynthesis, and physical state of membrane lipids occurring upon aging of Mycoplasma hominis cultures.", "content": "During the progression of Mycoplasma hominis cultures from the early logarithmic phase to the stationary phase of growth, the total phospholipid content of the cell membranes decreased. Measurement of the amount of the various phospholipids during the growth cycle showed that a decrease in the phosphatidylglycerol (PG) content, accompanied by an increase in the phosphatidic acid content, occurred upon aging of the culture. Pulse labeling experiments revealed that the PG, once formed, is relatively stable, undergoing no detectable turnover in growing cultures of M. hominis. No changes in the fatty acid composition of the membrane phospholipids were observed on aging of the culture, with palmitic acid predominating throughout the growth cycle. The preferential incorporation of palmitate into the phospholipid fraction is apparently caused by the higher activity of the membrane-bound acyl-coenzyme A (CoA):alpha-glycerophosphate transacylase with palmityl-CoA rather than with oleyl-CoA as substrate. The activity of the soluble acyl-CoA synthetase was the same whether palmitate or oleate served as substate. M. hominis membrane preparations contained a PG-synthetase system catalyzing the incorporation of L-alpha-glycerol-3-phosphate into PG. The activity of the PG synthetase system was markedly dependent on the age of the culture, being highest in cells from the early exponential phase of growth while declining sharply thereafter, and thus probably responsible, in part, for the decrease in PG content upon aging of the cells. Electron paramagnetic resonance spectra of a spin-labeled fatty acid incorporated in M. hominis membranes revealed a marked decrease in the freedom of motion of the spin label on aging of the culture. It is proposed that this decrease is due primarily to the decrease in the lipid-to-protein ratio of the membranes and has a marked effect on the activity of membrane-associated enzymes and transport systems.", "contents": "Changes in composition, biosynthesis, and physical state of membrane lipids occurring upon aging of Mycoplasma hominis cultures. During the progression of Mycoplasma hominis cultures from the early logarithmic phase to the stationary phase of growth, the total phospholipid content of the cell membranes decreased. Measurement of the amount of the various phospholipids during the growth cycle showed that a decrease in the phosphatidylglycerol (PG) content, accompanied by an increase in the phosphatidic acid content, occurred upon aging of the culture. Pulse labeling experiments revealed that the PG, once formed, is relatively stable, undergoing no detectable turnover in growing cultures of M. hominis. No changes in the fatty acid composition of the membrane phospholipids were observed on aging of the culture, with palmitic acid predominating throughout the growth cycle. The preferential incorporation of palmitate into the phospholipid fraction is apparently caused by the higher activity of the membrane-bound acyl-coenzyme A (CoA):alpha-glycerophosphate transacylase with palmityl-CoA rather than with oleyl-CoA as substrate. The activity of the soluble acyl-CoA synthetase was the same whether palmitate or oleate served as substate. M. hominis membrane preparations contained a PG-synthetase system catalyzing the incorporation of L-alpha-glycerol-3-phosphate into PG. The activity of the PG synthetase system was markedly dependent on the age of the culture, being highest in cells from the early exponential phase of growth while declining sharply thereafter, and thus probably responsible, in part, for the decrease in PG content upon aging of the cells. Electron paramagnetic resonance spectra of a spin-labeled fatty acid incorporated in M. hominis membranes revealed a marked decrease in the freedom of motion of the spin label on aging of the culture. It is proposed that this decrease is due primarily to the decrease in the lipid-to-protein ratio of the membranes and has a marked effect on the activity of membrane-associated enzymes and transport systems."}
{"id": "PMID:234421", "title": "l-amino acid oxidases of Proteus rettgeri.", "content": "Proteus rettgeri has been found to contain two separable 1-amino acid oxidases. Both enzymes are particulate in nature, neither being ribosomal bound. One of these enzymes appears to have broad specificity, being active toward monoaminomonocarboxylic, imino, aromatic, sulfur-containing, and beta-hydroxyamino acids. The other enzyme has more limited specificity, catalyzing the oxidative deamination of the basic amino acids and citrulline. The affinity of this oxidase for the various substrates at pH 7.6 in decreasing order is arginine, histidine, ornithine, citrulline, and lysine. This enzyme has a particularly high affinity for arginine (Km equal to 0.27 mM), and anomalous kinetics are observed with increasing substrate concentrations. When concentrations of arginine greater than 1.0mM were added to the reaction containing histidine, imidazole pyruvate formation was completely inhibited.", "contents": "l-amino acid oxidases of Proteus rettgeri. Proteus rettgeri has been found to contain two separable 1-amino acid oxidases. Both enzymes are particulate in nature, neither being ribosomal bound. One of these enzymes appears to have broad specificity, being active toward monoaminomonocarboxylic, imino, aromatic, sulfur-containing, and beta-hydroxyamino acids. The other enzyme has more limited specificity, catalyzing the oxidative deamination of the basic amino acids and citrulline. The affinity of this oxidase for the various substrates at pH 7.6 in decreasing order is arginine, histidine, ornithine, citrulline, and lysine. This enzyme has a particularly high affinity for arginine (Km equal to 0.27 mM), and anomalous kinetics are observed with increasing substrate concentrations. When concentrations of arginine greater than 1.0mM were added to the reaction containing histidine, imidazole pyruvate formation was completely inhibited."}
{"id": "PMID:234422", "title": "Cyanide production from glycine by a homogenate from a Pseudomonas species.", "content": "A cell-free preparation with cyanide-producing activity was obtained from a bacterium, strain C, of the genus Pseudomonas. To preserve activity, an oxidizing agent, e.g., phenazine methosulphage (PMS), had to be added to the cell suspension before disruption by sonic treatment. By the procedure described, a total homogenate made from a 15% (wet weight) bacterial suspension in tris(hydroxymethyl)aminomethane-hydrochloride buffer (0.05 M, pH 8.2) and with PMS (0.4mM) exhibited about 8% of the activity obtained from a suspension of untreated bacteria. In the presence of flavine-adenine dinucleotide (0.3 mM) and PMS (0.4mM), the activity was augmented to about 16% of that of the intact cells. By gradient centrifugation the homogenate was separated into three fractions. The main enzyme activity was associated with those fractions which by electron microscopy were found to consist of membranous structures.", "contents": "Cyanide production from glycine by a homogenate from a Pseudomonas species. A cell-free preparation with cyanide-producing activity was obtained from a bacterium, strain C, of the genus Pseudomonas. To preserve activity, an oxidizing agent, e.g., phenazine methosulphage (PMS), had to be added to the cell suspension before disruption by sonic treatment. By the procedure described, a total homogenate made from a 15% (wet weight) bacterial suspension in tris(hydroxymethyl)aminomethane-hydrochloride buffer (0.05 M, pH 8.2) and with PMS (0.4mM) exhibited about 8% of the activity obtained from a suspension of untreated bacteria. In the presence of flavine-adenine dinucleotide (0.3 mM) and PMS (0.4mM), the activity was augmented to about 16% of that of the intact cells. By gradient centrifugation the homogenate was separated into three fractions. The main enzyme activity was associated with those fractions which by electron microscopy were found to consist of membranous structures."}
{"id": "PMID:234423", "title": "Metabolism of prostaglandins E, A, and C in serum.", "content": "Three prostaglandin-metabolizing enzymes were detected in human serum. One enzyme was a dehydrase that converted prostaglandin E to prostaglandin A, the second was a prostaglandin A isomerase that converted prostaglandin A to prostaglandin C and the third was a prostaglandin C isomerase that converted prostaglandin C to prostaglandin B. All three were inactivated by sulfhydryl blocking agents. In human serum, only prostaglandin C isomerase had high activity, whereas the two other enzymes had very low activity. In rabbit serum both isomerases were very active, but dehydrase activity could not be detected. Prostaglandin C isomerase activity was also found in crystallized human serum albumin and rabbit serum albumin.", "contents": "Metabolism of prostaglandins E, A, and C in serum. Three prostaglandin-metabolizing enzymes were detected in human serum. One enzyme was a dehydrase that converted prostaglandin E to prostaglandin A, the second was a prostaglandin A isomerase that converted prostaglandin A to prostaglandin C and the third was a prostaglandin C isomerase that converted prostaglandin C to prostaglandin B. All three were inactivated by sulfhydryl blocking agents. In human serum, only prostaglandin C isomerase had high activity, whereas the two other enzymes had very low activity. In rabbit serum both isomerases were very active, but dehydrase activity could not be detected. Prostaglandin C isomerase activity was also found in crystallized human serum albumin and rabbit serum albumin."}
{"id": "PMID:234424", "title": "Isolation and characterization of a ribonuclease from human leukemic blood cells specific for ribonucleic acid of ribonucleic acid-deoxyribonucleic acid hybrid molecules.", "content": "A ribonuclease that specifically hydrolyzes RNA in RNA. DNA hybrids has been purified more than 100-fold from human acute leukemic white blood cells. The molecular weight of this enzyme has been estimated as 80,000 by glycerol gradient centrifugation. It requires Mg-2plus for activity and is inhibited by N-ethylmaleimide. The optimum activity is observed at pH 8 (37 DEGREES). It is a heat-labile protein, t 1/2 at 50 degrees being 2 min. Among the substrates examined, (A)n X (dT)m, (I)n X (DC)m, and PHIX-174 DNA X RNA were hydrolyzed efficiently. (U)n X (dA)m showed a slight substrate activity, while (c) n X (dG) m and (G)n X (dC)m were not significantly hydrolyzed. The enzyme is an endonuclease and does not require RNA ends in the substrate molecule. It is capable of converting more than 95% of the RNA portions in hybrid substrates into acid-soluble products which are mono- and oligonucleotides terminated in 3'-OH and 5'-phosphate.", "contents": "Isolation and characterization of a ribonuclease from human leukemic blood cells specific for ribonucleic acid of ribonucleic acid-deoxyribonucleic acid hybrid molecules. A ribonuclease that specifically hydrolyzes RNA in RNA. DNA hybrids has been purified more than 100-fold from human acute leukemic white blood cells. The molecular weight of this enzyme has been estimated as 80,000 by glycerol gradient centrifugation. It requires Mg-2plus for activity and is inhibited by N-ethylmaleimide. The optimum activity is observed at pH 8 (37 DEGREES). It is a heat-labile protein, t 1/2 at 50 degrees being 2 min. Among the substrates examined, (A)n X (dT)m, (I)n X (DC)m, and PHIX-174 DNA X RNA were hydrolyzed efficiently. (U)n X (dA)m showed a slight substrate activity, while (c) n X (dG) m and (G)n X (dC)m were not significantly hydrolyzed. The enzyme is an endonuclease and does not require RNA ends in the substrate molecule. It is capable of converting more than 95% of the RNA portions in hybrid substrates into acid-soluble products which are mono- and oligonucleotides terminated in 3'-OH and 5'-phosphate."}
{"id": "PMID:234425", "title": "Characterization of particulate and soluble guanylate cyclases from rat lung.", "content": "Rat lung homogenates contained significant amounts of guanylate cyclase activity in both 100,000 times g (60 min) particulate and supernatant fractions. In the presence of detergent, the particulate fraction contained 40% as much activity as did the supernatant fraction. Detergent-dispersed particulate and partially purified soluble guanylate cyclase preparations were characterized with respect to divalent cation requirements, divalent cation interactions, kinetic behavior, and gel filtration profiles. Both soluble and particulate guanylate cyclases required divalent cation for activity. The soluble preparation was 10 times more active in the presence of Mn-2plus than in the presence of Mg-2plus or Ca-2plus and no detectable activity was seen with Ba-2plus or Sr-2plus. Particulate guanylate cyclase activity was detectable only in the presence of Mn-2plus. Both enzyme preparations required Mn-2plus in excess of GTP for optimal activity at subsaturating amounts of GTP. At near-saturating GTP, the soluble enzyme required excess Mn-2plus, but the particulate enzyme did not. For kinetic analyses the enzymes were considered to require two substrates: metal-GTP and Me-2plus. Apparent negative cooperative behavior was seen with the soluble enzyme when excess Mn-2plus (in excess of GTP) was varied from 0.01 to 0.2 mM; above 0.2 mM excess Mn-2plus classical kinetic behavior was seen with an apparent KMn-2plus of 0.2 mM at near-saturating MnGTP. Similar studies using the particulate preparation yielded only classical kinetic behavior, but the apparent KMn-2plus decreased to near zero when MnGTP was near-saturating. Kinetic patterns for the particulate and soluble enzymes also differed when reciprocal initial velocities were plotted as a function of reciprocal MnGTP concentrations; classical kinetic behavior was seen with the soluble enzyme with an apparent KMnGTP of about 12 muM (at near-saturating excess Mn-2plus), whereas apparent positive cooperative behavior was seen with the particulate preparation (Hill coefficient equals 1.6, S0.5 EQUALS 70 MUM. Ca-2plus \"activation\" of soluble guanylate cyclase was related to the Mn-2plus:GTP ratio. Activation was most apparent when saturating amounts of Mn-2plus and MnGTP. At relatively high concentrations of Ca-2plus (0.1 to 4 mM), the addition of 10 muM Mn-2plus resulted in a 3- to 5-fold increase in soluble guanylate cyclase activity. In contrast, Ca-2plus sharply inhibited particulate guanylate cyclase activity. Gel filtration profiles of particulate and soluble preparations indicated differences in physical properties of the enzymes. As estimated by gel filtration, particulate (detergent-dispersed)evels. Here, removal of renal tissue is contraindicated. In all renal hy", "contents": "Characterization of particulate and soluble guanylate cyclases from rat lung. Rat lung homogenates contained significant amounts of guanylate cyclase activity in both 100,000 times g (60 min) particulate and supernatant fractions. In the presence of detergent, the particulate fraction contained 40% as much activity as did the supernatant fraction. Detergent-dispersed particulate and partially purified soluble guanylate cyclase preparations were characterized with respect to divalent cation requirements, divalent cation interactions, kinetic behavior, and gel filtration profiles. Both soluble and particulate guanylate cyclases required divalent cation for activity. The soluble preparation was 10 times more active in the presence of Mn-2plus than in the presence of Mg-2plus or Ca-2plus and no detectable activity was seen with Ba-2plus or Sr-2plus. Particulate guanylate cyclase activity was detectable only in the presence of Mn-2plus. Both enzyme preparations required Mn-2plus in excess of GTP for optimal activity at subsaturating amounts of GTP. At near-saturating GTP, the soluble enzyme required excess Mn-2plus, but the particulate enzyme did not. For kinetic analyses the enzymes were considered to require two substrates: metal-GTP and Me-2plus. Apparent negative cooperative behavior was seen with the soluble enzyme when excess Mn-2plus (in excess of GTP) was varied from 0.01 to 0.2 mM; above 0.2 mM excess Mn-2plus classical kinetic behavior was seen with an apparent KMn-2plus of 0.2 mM at near-saturating MnGTP. Similar studies using the particulate preparation yielded only classical kinetic behavior, but the apparent KMn-2plus decreased to near zero when MnGTP was near-saturating. Kinetic patterns for the particulate and soluble enzymes also differed when reciprocal initial velocities were plotted as a function of reciprocal MnGTP concentrations; classical kinetic behavior was seen with the soluble enzyme with an apparent KMnGTP of about 12 muM (at near-saturating excess Mn-2plus), whereas apparent positive cooperative behavior was seen with the particulate preparation (Hill coefficient equals 1.6, S0.5 EQUALS 70 MUM. Ca-2plus \"activation\" of soluble guanylate cyclase was related to the Mn-2plus:GTP ratio. Activation was most apparent when saturating amounts of Mn-2plus and MnGTP. At relatively high concentrations of Ca-2plus (0.1 to 4 mM), the addition of 10 muM Mn-2plus resulted in a 3- to 5-fold increase in soluble guanylate cyclase activity. In contrast, Ca-2plus sharply inhibited particulate guanylate cyclase activity. Gel filtration profiles of particulate and soluble preparations indicated differences in physical properties of the enzymes. As estimated by gel filtration, particulate (detergent-dispersed)evels. Here, removal of renal tissue is contraindicated. In all renal hy"}
{"id": "PMID:234426", "title": "Effects of cations on guanylate cyclase of sea urchin sperm.", "content": "Mn2+ and to some degree Fe2+, but not Mg+, Ca2+, ba2+, Sr2+, Co2+, Ni2+, La3+, or Fe3+ were able to serve as effective metal cofactors for sea urchin sperm guanylate cyclase. The apparent Michaelis constant for Mn2+ in the presence of 0.25 mM MnGTP was 0.23 mM. In the presence of a fixed free mn2+ concentration, variation in mngTP resulted in sigmoid velocity-substrate plots and in reciprocal plots that were concave upward. These positive cooperative patterns were observed at both pH 7.0 and 7.8 and in the presence or absence of Triton X-100. When Mn2+ and GTP were equimolar, Ca2+, Ba2+, Sr2+, and Mg2+ increased apparent guanylate cyclase activity. This increase in enzyme activity at least could be accounted for partially by an increase in free Mn2+ concentration caused by the complex formation of GTP with the added metals. However, even at relatively low GTP concentrations and with Mn2+ concentrations in excess of GTP, Ca2+, Sr2+, and Ba2+ significantly increased guanosine 3':5'-monophosphate production. As the total GTP concentration was increased, the degree of stimulation in the presence of Ca2+ decreased, despite maintenance of a fixed total concentration of Ca2+ and a fixed free concentration of Mn2+, suggesting that the concentration of CaGTP and MnGTP were determining factors in the observed response. The concave upward reciprocal plots of velocity against MnGTP concentration were changed to linear plots in the presence of CaGTP or SrGTP. These results suggest that sea urchin sperm guanylate cyclase contains multiple nucleotide binding sites and that stimulation of guanosine 3':5'-monophosphate synthesis by Ca2+, Sr2+, and perhaps other metals may reflect interaction of a metal-GTP complex with enzyme as either an effector or a substrate.", "contents": "Effects of cations on guanylate cyclase of sea urchin sperm. Mn2+ and to some degree Fe2+, but not Mg+, Ca2+, ba2+, Sr2+, Co2+, Ni2+, La3+, or Fe3+ were able to serve as effective metal cofactors for sea urchin sperm guanylate cyclase. The apparent Michaelis constant for Mn2+ in the presence of 0.25 mM MnGTP was 0.23 mM. In the presence of a fixed free mn2+ concentration, variation in mngTP resulted in sigmoid velocity-substrate plots and in reciprocal plots that were concave upward. These positive cooperative patterns were observed at both pH 7.0 and 7.8 and in the presence or absence of Triton X-100. When Mn2+ and GTP were equimolar, Ca2+, Ba2+, Sr2+, and Mg2+ increased apparent guanylate cyclase activity. This increase in enzyme activity at least could be accounted for partially by an increase in free Mn2+ concentration caused by the complex formation of GTP with the added metals. However, even at relatively low GTP concentrations and with Mn2+ concentrations in excess of GTP, Ca2+, Sr2+, and Ba2+ significantly increased guanosine 3':5'-monophosphate production. As the total GTP concentration was increased, the degree of stimulation in the presence of Ca2+ decreased, despite maintenance of a fixed total concentration of Ca2+ and a fixed free concentration of Mn2+, suggesting that the concentration of CaGTP and MnGTP were determining factors in the observed response. The concave upward reciprocal plots of velocity against MnGTP concentration were changed to linear plots in the presence of CaGTP or SrGTP. These results suggest that sea urchin sperm guanylate cyclase contains multiple nucleotide binding sites and that stimulation of guanosine 3':5'-monophosphate synthesis by Ca2+, Sr2+, and perhaps other metals may reflect interaction of a metal-GTP complex with enzyme as either an effector or a substrate."}
{"id": "PMID:234427", "title": "Activation and control of factor VII by activated factor X and thrombin. Isolation and characterization of a single chain form of factor VII.", "content": "Factor VII purified as previously described, was found to consist of two polypeptide chains joined by disulfide bridges. We now report the isolation and 200,000-fold purification of a single chain form of Factor VII. This was accomplished by protecting the molecule against proteolysis by including benzamidine during the entire purification. The purification was essentially as previously reported except that barium cirtate was substituted for barium sulfate as an absorbant for Factor VII as it resulted in a 4-fold increase in yield. Single chain Factor VII is rapidly hydrolyzed by Factor Xa in the presence of calcium ions and phospholipids, and by thrombin, to a two-chain form which possesses at least 85 times the Factor VII clotting activity of the single chain species. The two-chain form of the enzyme requires tissue factor in order to activate Factor X. From the observed rates of activation of Factor VII by Xa in the presence of calcium ions and phospholipids, it was calculated that at approximately physiological concentration, Factor VII activity would increase at an initial rate of 20-fold per min; this reaction is sufficiently rapid to constitute a feedback control mechanism. The action of thrombin is approximately 40-fold slower under these conditions. Diisopropylphosphorofluoridate inactivates the single chain and two-chain forms of Factor VII at approximately equal rates. After inhibition, the single chain species could be cleaved but not activated by proteolysis.", "contents": "Activation and control of factor VII by activated factor X and thrombin. Isolation and characterization of a single chain form of factor VII. Factor VII purified as previously described, was found to consist of two polypeptide chains joined by disulfide bridges. We now report the isolation and 200,000-fold purification of a single chain form of Factor VII. This was accomplished by protecting the molecule against proteolysis by including benzamidine during the entire purification. The purification was essentially as previously reported except that barium cirtate was substituted for barium sulfate as an absorbant for Factor VII as it resulted in a 4-fold increase in yield. Single chain Factor VII is rapidly hydrolyzed by Factor Xa in the presence of calcium ions and phospholipids, and by thrombin, to a two-chain form which possesses at least 85 times the Factor VII clotting activity of the single chain species. The two-chain form of the enzyme requires tissue factor in order to activate Factor X. From the observed rates of activation of Factor VII by Xa in the presence of calcium ions and phospholipids, it was calculated that at approximately physiological concentration, Factor VII activity would increase at an initial rate of 20-fold per min; this reaction is sufficiently rapid to constitute a feedback control mechanism. The action of thrombin is approximately 40-fold slower under these conditions. Diisopropylphosphorofluoridate inactivates the single chain and two-chain forms of Factor VII at approximately equal rates. After inhibition, the single chain species could be cleaved but not activated by proteolysis."}
{"id": "PMID:234428", "title": "Solvent accessibility in folded proteins. Studies of hydrogen exchange in trypsin.", "content": "In a native protein, the exchange of a peptide amide proton with solvent occurs by one of two pathways, either directly from the folded protein, or via unfolding, exchange taking place from the unfolded protein. From the thermal unfolding rate constants, the contribution of unfolding to the over-all kinetics as a function of solvent and temperature has been determined. Exchange involving unfolding of the protein is characterized by a high activation energy, in the range of 50 to 60 Cal per mol. The activiation energy (Eapp) of the rates of exchange directly from the folded protein is approximately 20 to 25 Cal per mol. Because for the proton transfer step, Eapp approximately equal to 20  Cal per mol, the activation energy for any contributing protein conformational process(es) is approximately equal to 0 to 5 Cal per mol. Most, if not all, of the peptide amide protons in a folded protein can exchange directly with solvent without the protein unfolding. The number of \"slowly\" exchanging protons at a given condition of pH and temperature is not related to a discrete structural unit, but rather to the distribution of observed rates within the broader distribution of actual rates. The large attenuation of hydrogen exchange rates in folded proteins, resulting in a distribution of first order rates over 6 orders of magnitude, is primarily due to the effects of restricted solvent accessibility of labile protons in the three-dimensional structure. Any protein conformational process, such as protein fluctuations, invoked to explain the solvent accessibility must be of low activation energy and attenuated by ethanol and other co-solvents (Woodward, C. K., Ellis, L. M., and Rosenberg, A. (1974) J. Biol. Chem. 250, 440-444).", "contents": "Solvent accessibility in folded proteins. Studies of hydrogen exchange in trypsin. In a native protein, the exchange of a peptide amide proton with solvent occurs by one of two pathways, either directly from the folded protein, or via unfolding, exchange taking place from the unfolded protein. From the thermal unfolding rate constants, the contribution of unfolding to the over-all kinetics as a function of solvent and temperature has been determined. Exchange involving unfolding of the protein is characterized by a high activation energy, in the range of 50 to 60 Cal per mol. The activiation energy (Eapp) of the rates of exchange directly from the folded protein is approximately 20 to 25 Cal per mol. Because for the proton transfer step, Eapp approximately equal to 20  Cal per mol, the activation energy for any contributing protein conformational process(es) is approximately equal to 0 to 5 Cal per mol. Most, if not all, of the peptide amide protons in a folded protein can exchange directly with solvent without the protein unfolding. The number of \"slowly\" exchanging protons at a given condition of pH and temperature is not related to a discrete structural unit, but rather to the distribution of observed rates within the broader distribution of actual rates. The large attenuation of hydrogen exchange rates in folded proteins, resulting in a distribution of first order rates over 6 orders of magnitude, is primarily due to the effects of restricted solvent accessibility of labile protons in the three-dimensional structure. Any protein conformational process, such as protein fluctuations, invoked to explain the solvent accessibility must be of low activation energy and attenuated by ethanol and other co-solvents (Woodward, C. K., Ellis, L. M., and Rosenberg, A. (1974) J. Biol. Chem. 250, 440-444)."}
{"id": "PMID:234429", "title": "The solvent dependence of hydrogen exchange kinetics of folded proteins.", "content": "The effects of ethanol, ethylene glycol, dioxane, and other organic co-solvents upon the hydrogen exchange rates of randomly coiled oxidized RNase, native RNase, and native trypsin have been measured. The exchange rate of oxidized RNase, the model compound for the proton transfer step in hydrogen exchange, is decreased by all of the co-solvents studied at temperatures in the range 3-20 degrees. This has been ascribed to the combined effects of the disruption of peptide bond solvation due to a reduction in the concentration of water, and of changes in [OH-] ion concentration due to changes in the acid dissociation constant of water, Kw. The solvent dependence for both native RNase and native trypsin is similar in all of the solvents studied. At a low temperature (3-20 degrees), the exchange rates go through a minimum as the solvent concentration is increased. At higher temperatures (20-35 degrees) the exchange rates are increased at all concentrations of the co-solvent. The apparent rate minimum at lower temperatures is due to two opposing effects. Co-solvents decrease the rate of exchange that occurs directly from the folded molecule. At higher concentrations and higer temperature. The decrease in rates for exchange directly from folded protein is primarily due to the effects on the proton transfer step, and not to binding or the solvent effects on protein structure. The solvents used in this study have no apparent effect on conformational processes contributing to the hydrogen exchange process in folded proteins.", "contents": "The solvent dependence of hydrogen exchange kinetics of folded proteins. The effects of ethanol, ethylene glycol, dioxane, and other organic co-solvents upon the hydrogen exchange rates of randomly coiled oxidized RNase, native RNase, and native trypsin have been measured. The exchange rate of oxidized RNase, the model compound for the proton transfer step in hydrogen exchange, is decreased by all of the co-solvents studied at temperatures in the range 3-20 degrees. This has been ascribed to the combined effects of the disruption of peptide bond solvation due to a reduction in the concentration of water, and of changes in [OH-] ion concentration due to changes in the acid dissociation constant of water, Kw. The solvent dependence for both native RNase and native trypsin is similar in all of the solvents studied. At a low temperature (3-20 degrees), the exchange rates go through a minimum as the solvent concentration is increased. At higher temperatures (20-35 degrees) the exchange rates are increased at all concentrations of the co-solvent. The apparent rate minimum at lower temperatures is due to two opposing effects. Co-solvents decrease the rate of exchange that occurs directly from the folded molecule. At higher concentrations and higer temperature. The decrease in rates for exchange directly from folded protein is primarily due to the effects on the proton transfer step, and not to binding or the solvent effects on protein structure. The solvents used in this study have no apparent effect on conformational processes contributing to the hydrogen exchange process in folded proteins."}
{"id": "PMID:234430", "title": "Proton magnetic resonance studies of alpha-keto acids.", "content": "Pulsed Fourier transform proton magnetic resonance was used to study alpha-ketoglutaramic, and several other alpha-keto acids in aqueous solutions as a function of pH. Most alpha-keto acids were found to exist in equilibrium with the hydrate (gem-doil). The equilibrium position favors the nonhydrated alphs-keto acid at neutral pH, but at low pH values (below the pKa of the alpha-carboxylic acid group) the hydrate predominates. We found evidence that alpha-ketoglutaric acid exists in a third equilibrium form which is assigned to the lactol. alpha-Ketoglutaramic acid (the alpha-keto acid analog of glutamine) which is known to exist predominantly in a cyclic form at pH 7.0 was shown to exist as a cyclic structure over a wide pH range. However, the cyclic form is an equilibrium mixture of 2-pyrrolidone-5-hydroxy-5-carboxylic and 1-pyrrolin-2-one-5-carboxylic acids.", "contents": "Proton magnetic resonance studies of alpha-keto acids. Pulsed Fourier transform proton magnetic resonance was used to study alpha-ketoglutaramic, and several other alpha-keto acids in aqueous solutions as a function of pH. Most alpha-keto acids were found to exist in equilibrium with the hydrate (gem-doil). The equilibrium position favors the nonhydrated alphs-keto acid at neutral pH, but at low pH values (below the pKa of the alpha-carboxylic acid group) the hydrate predominates. We found evidence that alpha-ketoglutaric acid exists in a third equilibrium form which is assigned to the lactol. alpha-Ketoglutaramic acid (the alpha-keto acid analog of glutamine) which is known to exist predominantly in a cyclic form at pH 7.0 was shown to exist as a cyclic structure over a wide pH range. However, the cyclic form is an equilibrium mixture of 2-pyrrolidone-5-hydroxy-5-carboxylic and 1-pyrrolin-2-one-5-carboxylic acids."}
{"id": "PMID:234431", "title": "Prostaglandin metabolism. II. Identification of two 15-hydroxyprostaglandin dehydrogenase types.", "content": "Homogenates of several mammalian tissues were measured by radioimmunoassay for 15-hydroxyprostaglandin dehydrogenase activity. Two types of enzyme activity were detected. One, which used NAD-plus as cofactor much more effectively than NADP-lus, was found in monkey lung, heart, liver, kidney, and spleen and in chicken heart and dog lung. A second type, which uses NADP-plus as a cofactor more effectively than NAD-plus, was found in monkey and human brain and red blood cells and in swine kidney. These two types of 15-hydroxyprostaglandin dehydrogenase were partially purified from monkey brain and chicken heart. In addition to different cofactor requirements, the two partially purified enzymes could be distinguished by chromatographic properties, their relative affinities for prostaglandin I2 and F2alpha, and their sensitivities to inhibition by reduced pyridine nucleotides, thyroid hormones, and prostaglandin B2.", "contents": "Prostaglandin metabolism. II. Identification of two 15-hydroxyprostaglandin dehydrogenase types. Homogenates of several mammalian tissues were measured by radioimmunoassay for 15-hydroxyprostaglandin dehydrogenase activity. Two types of enzyme activity were detected. One, which used NAD-plus as cofactor much more effectively than NADP-lus, was found in monkey lung, heart, liver, kidney, and spleen and in chicken heart and dog lung. A second type, which uses NADP-plus as a cofactor more effectively than NAD-plus, was found in monkey and human brain and red blood cells and in swine kidney. These two types of 15-hydroxyprostaglandin dehydrogenase were partially purified from monkey brain and chicken heart. In addition to different cofactor requirements, the two partially purified enzymes could be distinguished by chromatographic properties, their relative affinities for prostaglandin I2 and F2alpha, and their sensitivities to inhibition by reduced pyridine nucleotides, thyroid hormones, and prostaglandin B2."}
{"id": "PMID:234432", "title": "Reversible modification of arginine residues. Application to sequence studies by restriction of tryptic hydrolysis to lysine residues.", "content": "1, 2-Cyclohexanedione reacts specifically with the guanidino group of arginine or arginine residues at pH 8 to 9 in sodium borate buffer in the temperature range of 25-40 degrees. The single product, N-7, N-8-(1,2-dihydroxycyclohex-1,2-ylene)-L-arginine (DHCH-arginine) is stable in acidic solutions and in borate buffers (pH 8 to 9). DHCH-Arginine is converted to N-7-adipyl-L-arginine by periodate oxidation. The structures of the two compounds were elucidated by chemical and physicochemical means. Arginine or arginyl residues can be regenerated quantitatively from DHCH-arginine by incubation at 37 degrees in hydroxylamine buffer at pH 7.0 FOR 7 TO 8 hours. Analysis of native egg white lysozyme and native as well as oxidized bovine pancreatic RNase, which were treated with cyclohexanedione, showed that only arginine residues were modified. The utility of the method in sequence studies was shown on oxidized bovine pancreatic ribonuclease A. Arginine modification was complete in 2 hours at 35 degrees in borate buffer at pH 9.0 with a 15-fold molar excess of the reagent. The derived peptides showed that tryptic hydrolysis was entirely limited to peptide bonds involving lysine residues, as shown both by two-dimensional peptide patterns and by isolation of the resulting peptides. The stability of DHCH-arginyl residues permits isolation of labeled peptides.", "contents": "Reversible modification of arginine residues. Application to sequence studies by restriction of tryptic hydrolysis to lysine residues. 1, 2-Cyclohexanedione reacts specifically with the guanidino group of arginine or arginine residues at pH 8 to 9 in sodium borate buffer in the temperature range of 25-40 degrees. The single product, N-7, N-8-(1,2-dihydroxycyclohex-1,2-ylene)-L-arginine (DHCH-arginine) is stable in acidic solutions and in borate buffers (pH 8 to 9). DHCH-Arginine is converted to N-7-adipyl-L-arginine by periodate oxidation. The structures of the two compounds were elucidated by chemical and physicochemical means. Arginine or arginyl residues can be regenerated quantitatively from DHCH-arginine by incubation at 37 degrees in hydroxylamine buffer at pH 7.0 FOR 7 TO 8 hours. Analysis of native egg white lysozyme and native as well as oxidized bovine pancreatic RNase, which were treated with cyclohexanedione, showed that only arginine residues were modified. The utility of the method in sequence studies was shown on oxidized bovine pancreatic ribonuclease A. Arginine modification was complete in 2 hours at 35 degrees in borate buffer at pH 9.0 with a 15-fold molar excess of the reagent. The derived peptides showed that tryptic hydrolysis was entirely limited to peptide bonds involving lysine residues, as shown both by two-dimensional peptide patterns and by isolation of the resulting peptides. The stability of DHCH-arginyl residues permits isolation of labeled peptides."}
{"id": "PMID:234433", "title": "Effects of ethidium bromide on the respiratory chain and oligomycin-sensitive adenosine triphosphatase in purified mitochondria from the cellular slime mold Dicyostelium discoideum.", "content": "Mitochondria were isolated from the cellular slime mold. Dictyoostelium discoideum, and partially purified by sucrose density gradient fractionation. The most purified mitochondrial fraction from the gradient contained essentially no contaminating lysosomes and minimal amounts of contaminating peroxisomes as determined by the marker enzymes N-acetyl-glucosaminidase and catalase. A mitochondrial fraction with the same amount of lysosomal and peroxisomal contamination was also isolated from cells which had been treated with ethidium bromide for 5 days. The most purified mitochondrial fraction from control and ethidium bromide-treated cells had an identical buoyant density of 1.181 to 1.182 g per ml, suggesting that treatment with the drug does not result in any drastic structural changes in the mitochondrial membrane which would affect its density. In the purified mitochondria from ethidium bromide-treated cells, the content of cytochromes a-a3 was decreased over 80% and that of cytochrome oxidase and oligomycin sensitive ATPase were reduced approximately 50%. By contrast, the specific activities of NADH and succinate dehydrogenases were identical in the purified mitochondria from control and ethidium bromide-treated cells. Previously, we had reported that the specific activities of these two enzymes had nearly doubled in whole cells maintained in ethidium bromide for a time equivalent to six or seven generations after growth had stopped (Stuchell, R. N., Weinstein, B. I., and Beattie, D. S. (1973) Fed. Eur. Biochem. Coc Lett. 37, 23-26). These results suggest that continued formation of new mitochondrial membranes, with an identical complement of succinate and NADH dehydrogenases, must occur despite the cessation of cell growth which occurs as a result of the ethidium bromide induced loss of mitochondrial enzymes. Consequently, the amount of mitochondria, or mitochondrial protein per cell, calculated from the activity of NADH and succinate dehydrogenases has increased nearly 50%. Possible models to explain the control of mitochondrial biogenesis are discussed to explain these results.", "contents": "Effects of ethidium bromide on the respiratory chain and oligomycin-sensitive adenosine triphosphatase in purified mitochondria from the cellular slime mold Dicyostelium discoideum. Mitochondria were isolated from the cellular slime mold. Dictyoostelium discoideum, and partially purified by sucrose density gradient fractionation. The most purified mitochondrial fraction from the gradient contained essentially no contaminating lysosomes and minimal amounts of contaminating peroxisomes as determined by the marker enzymes N-acetyl-glucosaminidase and catalase. A mitochondrial fraction with the same amount of lysosomal and peroxisomal contamination was also isolated from cells which had been treated with ethidium bromide for 5 days. The most purified mitochondrial fraction from control and ethidium bromide-treated cells had an identical buoyant density of 1.181 to 1.182 g per ml, suggesting that treatment with the drug does not result in any drastic structural changes in the mitochondrial membrane which would affect its density. In the purified mitochondria from ethidium bromide-treated cells, the content of cytochromes a-a3 was decreased over 80% and that of cytochrome oxidase and oligomycin sensitive ATPase were reduced approximately 50%. By contrast, the specific activities of NADH and succinate dehydrogenases were identical in the purified mitochondria from control and ethidium bromide-treated cells. Previously, we had reported that the specific activities of these two enzymes had nearly doubled in whole cells maintained in ethidium bromide for a time equivalent to six or seven generations after growth had stopped (Stuchell, R. N., Weinstein, B. I., and Beattie, D. S. (1973) Fed. Eur. Biochem. Coc Lett. 37, 23-26). These results suggest that continued formation of new mitochondrial membranes, with an identical complement of succinate and NADH dehydrogenases, must occur despite the cessation of cell growth which occurs as a result of the ethidium bromide induced loss of mitochondrial enzymes. Consequently, the amount of mitochondria, or mitochondrial protein per cell, calculated from the activity of NADH and succinate dehydrogenases has increased nearly 50%. Possible models to explain the control of mitochondrial biogenesis are discussed to explain these results."}
{"id": "PMID:234434", "title": "Deoxycytidine triphosphate deaminase of Salmonella typhimurium. Purification and characterization.", "content": "Deoxycytidine triphosphate deaminase (EC 3.5.4., dCTP aminohydrolase) of Salmonella typhimurium LT2 has been pruified 500-fold. The reaction requires the presence of Mg-2plus, Mn-2plus, Ca-2lus, or Co-2plus. Kinetics of the reaction with varying Mg-2plus concentrations, keeping the concentration of dCTP constant, suggests that the true substrate of the reaction is MgdCTP. The dependence of the rate of reaction on dCTP concentration in the presnece of 5-fold excess of Mg-2plus is sigmoid, with a Hill coefficient of 1.7. The enzyme is specifically inhibited by dTTP and dUTP. In the presence of increasing dTTP concentrations the sigmoidicity of the substrate saturation curves increases. With 0.2 and 0.4 mM dTTP the Hill coefficients are 2.6 and 3.0, respectively. Despite several attempts no dissociation of the substrate site and the inhibitor site of the enzyme was achieved.", "contents": "Deoxycytidine triphosphate deaminase of Salmonella typhimurium. Purification and characterization. Deoxycytidine triphosphate deaminase (EC 3.5.4., dCTP aminohydrolase) of Salmonella typhimurium LT2 has been pruified 500-fold. The reaction requires the presence of Mg-2plus, Mn-2plus, Ca-2lus, or Co-2plus. Kinetics of the reaction with varying Mg-2plus concentrations, keeping the concentration of dCTP constant, suggests that the true substrate of the reaction is MgdCTP. The dependence of the rate of reaction on dCTP concentration in the presnece of 5-fold excess of Mg-2plus is sigmoid, with a Hill coefficient of 1.7. The enzyme is specifically inhibited by dTTP and dUTP. In the presence of increasing dTTP concentrations the sigmoidicity of the substrate saturation curves increases. With 0.2 and 0.4 mM dTTP the Hill coefficients are 2.6 and 3.0, respectively. Despite several attempts no dissociation of the substrate site and the inhibitor site of the enzyme was achieved."}
{"id": "PMID:234435", "title": "Subunit interactions in aspartate transcarbamylase. Characterization of a complex between the catalytic and the regulatory subunits.", "content": "The complex formed when excess regulatory subunits (r2) of aspartate transcarbamylase is added to a dilute solution of the catalytic subunit (c3) has been further studied. By stabilizing the complex with saturating levels or r2, it was possible to perform ultracentrifugation in sucrose density gradients. The sedimentation coefficient of the complex (7.7 plus or minus 0.2 S) is intermediate between those of the catalytic subunit (5.8 S) and of the native enzyme (11.7 S). Consideration of the likely hydrodynamic properties of the complex suggests that this sedimentation coefficient may be consistent with the c3r6 structure previously proposed. The formation of c3r6 from c3 and r2 is readily reversible. At nonsaturating levels or r2, conversion to the native enzyme (c3r6) takes place. This conversion is inhibited by high concentrations of r2. The c3r6 complex shows Michaelis-Menten kinetics with a low Km for aspartate and considerable substrate inhibition. The pH activity profile at high aspartate concentrations is almost identical with that of the native enzyme. All of these observations suggest that c3r6 represents the relaxed (R) state of aspartate transcarbamylase. The insensitivity of c3r6 toward CTP or ATP can also be explained by considering c3r6 as a stabilized relaxed state. These properties of c3r6 have significant implications regarding the allosteric mechanism of the native enzyme.", "contents": "Subunit interactions in aspartate transcarbamylase. Characterization of a complex between the catalytic and the regulatory subunits. The complex formed when excess regulatory subunits (r2) of aspartate transcarbamylase is added to a dilute solution of the catalytic subunit (c3) has been further studied. By stabilizing the complex with saturating levels or r2, it was possible to perform ultracentrifugation in sucrose density gradients. The sedimentation coefficient of the complex (7.7 plus or minus 0.2 S) is intermediate between those of the catalytic subunit (5.8 S) and of the native enzyme (11.7 S). Consideration of the likely hydrodynamic properties of the complex suggests that this sedimentation coefficient may be consistent with the c3r6 structure previously proposed. The formation of c3r6 from c3 and r2 is readily reversible. At nonsaturating levels or r2, conversion to the native enzyme (c3r6) takes place. This conversion is inhibited by high concentrations of r2. The c3r6 complex shows Michaelis-Menten kinetics with a low Km for aspartate and considerable substrate inhibition. The pH activity profile at high aspartate concentrations is almost identical with that of the native enzyme. All of these observations suggest that c3r6 represents the relaxed (R) state of aspartate transcarbamylase. The insensitivity of c3r6 toward CTP or ATP can also be explained by considering c3r6 as a stabilized relaxed state. These properties of c3r6 have significant implications regarding the allosteric mechanism of the native enzyme."}
{"id": "PMID:234437", "title": "Concomitant changes in adenylate cyclase and cytolytic activities of lymphoid cells during graft versus host reaction.", "content": "Spleen cells from adult F1 hybrid mice undergoing the graft versus host reaction due to the inoculation of lymphoid cells of parental origin showed increased adenylate cyclase activity and cytolytic activity. A time-course study revealed that both the adenylate cyclase and cytolytic activities started increasing at Day 4 and reached maximum at Day 8 of initiation of the graft versus host reaction. Furthermore, the magnitude of both adenylate cyclase activation and cytolytic activity were dependent upon the number of parental cells injected into the F1 hybrid recipients. Elevated adenylate cyclase activity was also observed in spleen cells from irradiated animals undergoing the graft versus host reaction in which the nonspecific, but not the specific cytolytic activity was markedly depressed.", "contents": "Concomitant changes in adenylate cyclase and cytolytic activities of lymphoid cells during graft versus host reaction. Spleen cells from adult F1 hybrid mice undergoing the graft versus host reaction due to the inoculation of lymphoid cells of parental origin showed increased adenylate cyclase activity and cytolytic activity. A time-course study revealed that both the adenylate cyclase and cytolytic activities started increasing at Day 4 and reached maximum at Day 8 of initiation of the graft versus host reaction. Furthermore, the magnitude of both adenylate cyclase activation and cytolytic activity were dependent upon the number of parental cells injected into the F1 hybrid recipients. Elevated adenylate cyclase activity was also observed in spleen cells from irradiated animals undergoing the graft versus host reaction in which the nonspecific, but not the specific cytolytic activity was markedly depressed."}
{"id": "PMID:234438", "title": "Purification and characterization of two cellulases from auxin-treated pea epicotyls.", "content": "Two forms of beta-1,4-glucan 4-glucanohydrolase (EC 3.2.1.4) were extracted from growing regions of Pisum sativum epicotyls which had been treated with the auxin, (2,4-dichlorophenoxy)acetic acid. One cellulase is buffer-soluble, the other buffer-insoluble but extractable with high salt concentrations. Both enzymes catalyze endohydrolysis of carboxymethylcellulose with the same pH optimum (5.5 to 6.0). They were purified with the use of DEAE-cellulose chromatography, Sephadex gel filtration, and ultrafiltration. They are distinct proteins as characterized by: electrofocusing and disc gel electrophoresis (pI values = 5.2 and 6.9, respectively); mobility in sodium dodecyl sulfate polyacrylamide gels, fractionation on Sephadex, and sedimentation in the ultracentrifuge (mol wt = approximately 20,000 and 70,000, S values 2.63 and 3.73); and immunological properties. The buffer-soluble enzyme tends to dimerize on purification. Amino acid analyses show that the buffer-soluble enzyme is relatively rich in glycine, alanine, and valine and deficient in cystine, tryosine, and phenylalanine compared to the buffer-insoluble enzyme. The two cellulase activities were generated in approximately equal amounts after auxin treatment. Within 5 days their levels had increased at least 100-fold and they constituted about 0.1% of total cellular protein. Present data indicate that one is not derived from the other.", "contents": "Purification and characterization of two cellulases from auxin-treated pea epicotyls. Two forms of beta-1,4-glucan 4-glucanohydrolase (EC 3.2.1.4) were extracted from growing regions of Pisum sativum epicotyls which had been treated with the auxin, (2,4-dichlorophenoxy)acetic acid. One cellulase is buffer-soluble, the other buffer-insoluble but extractable with high salt concentrations. Both enzymes catalyze endohydrolysis of carboxymethylcellulose with the same pH optimum (5.5 to 6.0). They were purified with the use of DEAE-cellulose chromatography, Sephadex gel filtration, and ultrafiltration. They are distinct proteins as characterized by: electrofocusing and disc gel electrophoresis (pI values = 5.2 and 6.9, respectively); mobility in sodium dodecyl sulfate polyacrylamide gels, fractionation on Sephadex, and sedimentation in the ultracentrifuge (mol wt = approximately 20,000 and 70,000, S values 2.63 and 3.73); and immunological properties. The buffer-soluble enzyme tends to dimerize on purification. Amino acid analyses show that the buffer-soluble enzyme is relatively rich in glycine, alanine, and valine and deficient in cystine, tryosine, and phenylalanine compared to the buffer-insoluble enzyme. The two cellulase activities were generated in approximately equal amounts after auxin treatment. Within 5 days their levels had increased at least 100-fold and they constituted about 0.1% of total cellular protein. Present data indicate that one is not derived from the other."}
{"id": "PMID:234439", "title": "Soluble cytochrome P-450 from housefly microsomes. Partial purification and characterization of two hemoprotein forms.", "content": "Housefly microsomes contain two spectrally different forms of cytochrome P-450 which we have termed P-450 and P-450I. Methods have been developed for the fractionation and chromatographic purification of these two hemoprotein forms. Microsomes are solubilized first with Triton X-100 in the presence of glycerol, dithiothreitol, ethylenediaminetetra-acetic acid, and phenobarbital. Cytochrome P-450 is recovered in a floating pellet after the addition of 25% ammonium sulfate followed by centrifugation, whereas cytochrome P-450I remains in the 25% ammonium sulfate supernatant fluid. Cytochrome P-450 is purified further by Sephadez G-200 and DEAE-Sephadex A-50 column chromatography, which also allows the isolation of cytochrome b5 and NADPH-dependent cytochrome P-450 reductase in good yields and with little cross-contamination. Cytochrome P-450 apparently is free of cytochromes b5 and P-420 as well as of reductase and is obtained in a final yield of approximately 16% with a 6.9-fold purification. Its maximum absorbance is at 45 mn in the CO-difference spectrum and its average extinction coefficient is 103 cm-1 nm-1. Cytochrome P-450I is purified by Sephadex G-25 column chromatography but still contains some cytochromes b5 and P-420 as well as reductase. Its maximum absorbance is at 448.5 nm in the CO-difference spectrum and its extinction coefficient is 83 to 86 cm-1 mM-1. Both cytochromes hydroxylate type I substrates such as aminopyrine. Sufficient amounts of reductase are present in the cytochrome P-450I preparation to sustain activity, but the reductase has to be added to cytochrome P-450 in a reconstituted system for activity. Cytochrome P-450 is fairly stable, whereas cytochrome P-450I can be isolated only when protected by a substrate (phenobarbital). Detergent-solubilized housefly cytochromes P-450 and P-450I seem to correspond to either aggregates or oligomeric proteins. Cytochrome P-450 appears to correspond to a tetramer, each subunit having a molecular weight of 45,000, whereas cytochrome P-450I may correspond to an aggregate of at least 10 subunits. The cytochrome P-450 aggregate is dissociated by 6 M urea, but cytochrome P-450I remains as such.", "contents": "Soluble cytochrome P-450 from housefly microsomes. Partial purification and characterization of two hemoprotein forms. Housefly microsomes contain two spectrally different forms of cytochrome P-450 which we have termed P-450 and P-450I. Methods have been developed for the fractionation and chromatographic purification of these two hemoprotein forms. Microsomes are solubilized first with Triton X-100 in the presence of glycerol, dithiothreitol, ethylenediaminetetra-acetic acid, and phenobarbital. Cytochrome P-450 is recovered in a floating pellet after the addition of 25% ammonium sulfate followed by centrifugation, whereas cytochrome P-450I remains in the 25% ammonium sulfate supernatant fluid. Cytochrome P-450 is purified further by Sephadez G-200 and DEAE-Sephadex A-50 column chromatography, which also allows the isolation of cytochrome b5 and NADPH-dependent cytochrome P-450 reductase in good yields and with little cross-contamination. Cytochrome P-450 apparently is free of cytochromes b5 and P-420 as well as of reductase and is obtained in a final yield of approximately 16% with a 6.9-fold purification. Its maximum absorbance is at 45 mn in the CO-difference spectrum and its average extinction coefficient is 103 cm-1 nm-1. Cytochrome P-450I is purified by Sephadex G-25 column chromatography but still contains some cytochromes b5 and P-420 as well as reductase. Its maximum absorbance is at 448.5 nm in the CO-difference spectrum and its extinction coefficient is 83 to 86 cm-1 mM-1. Both cytochromes hydroxylate type I substrates such as aminopyrine. Sufficient amounts of reductase are present in the cytochrome P-450I preparation to sustain activity, but the reductase has to be added to cytochrome P-450 in a reconstituted system for activity. Cytochrome P-450 is fairly stable, whereas cytochrome P-450I can be isolated only when protected by a substrate (phenobarbital). Detergent-solubilized housefly cytochromes P-450 and P-450I seem to correspond to either aggregates or oligomeric proteins. Cytochrome P-450 appears to correspond to a tetramer, each subunit having a molecular weight of 45,000, whereas cytochrome P-450I may correspond to an aggregate of at least 10 subunits. The cytochrome P-450 aggregate is dissociated by 6 M urea, but cytochrome P-450I remains as such."}
{"id": "PMID:234440", "title": "p-Chlorphenylalanine effect on phenylalanine hydroxylase in hepatoma cells in culture.", "content": "We have investigated the p-chlorophenylalanine-dependent loss of phenylalanine hydroxylase activity in cultured hepatoma cells. The similarity of the effect of p-chlorophenylalanine on phenylalanine hydroxylase in the hepatoma cells and that reported from studies in vivo indicates that the loss of phenylalanine hydroxylase activity is due to a direct interaction of the amino acid analogue with the liver. We can find no evidence that the loss of phenylalanine hydroxylase activity is due to: a direct inactivation of the hydroxylase by p-chlorophenylalanine or an inhibitor produced by p-chlorophenylalanine treatment; an effect similar to that of p-fluorophenylalanine; or leakage of enzyme from the cells during p-chlorophenylalanine treatment. The data presented indicate: (a) the p-chlorophenylalanine effect is rather specific for phenylalanine hydroxylase; (b) following p-chlorophenylalanine removal, new protein synthesis is necessary for restoration of the hydroxylase activity; (c) the rate of loss of phenylalanine hydroxylase activity after the addition of p-chlorophenylalanine is much faster than the rate of restoration of the hydroxylase activity after removal of p-chlorophenylalanine; (d) even in the presence of p-chlorophenylalanine, hydrocortisone greatly stimulates the hydroxylase activity; (e) the cell density-dependent increase of phenylalanine hydroxylase activity is blocked by p-chlorophenylalanine. A discussion of the possible mechanisms of p-chlorophenylalanine-dependent loss of phenylalanine hydroxylase is presented. To measure very low leanine-dependent loss of phenylalanine hydroxylase is presented. To measure very low levels of phenylalanine hydroxylase activity, a new procedure, based on isotope dilution, was developed for isolating the tyrosine formed during the enzymatic reaction.", "contents": "p-Chlorphenylalanine effect on phenylalanine hydroxylase in hepatoma cells in culture. We have investigated the p-chlorophenylalanine-dependent loss of phenylalanine hydroxylase activity in cultured hepatoma cells. The similarity of the effect of p-chlorophenylalanine on phenylalanine hydroxylase in the hepatoma cells and that reported from studies in vivo indicates that the loss of phenylalanine hydroxylase activity is due to a direct interaction of the amino acid analogue with the liver. We can find no evidence that the loss of phenylalanine hydroxylase activity is due to: a direct inactivation of the hydroxylase by p-chlorophenylalanine or an inhibitor produced by p-chlorophenylalanine treatment; an effect similar to that of p-fluorophenylalanine; or leakage of enzyme from the cells during p-chlorophenylalanine treatment. The data presented indicate: (a) the p-chlorophenylalanine effect is rather specific for phenylalanine hydroxylase; (b) following p-chlorophenylalanine removal, new protein synthesis is necessary for restoration of the hydroxylase activity; (c) the rate of loss of phenylalanine hydroxylase activity after the addition of p-chlorophenylalanine is much faster than the rate of restoration of the hydroxylase activity after removal of p-chlorophenylalanine; (d) even in the presence of p-chlorophenylalanine, hydrocortisone greatly stimulates the hydroxylase activity; (e) the cell density-dependent increase of phenylalanine hydroxylase activity is blocked by p-chlorophenylalanine. A discussion of the possible mechanisms of p-chlorophenylalanine-dependent loss of phenylalanine hydroxylase is presented. To measure very low leanine-dependent loss of phenylalanine hydroxylase is presented. To measure very low levels of phenylalanine hydroxylase activity, a new procedure, based on isotope dilution, was developed for isolating the tyrosine formed during the enzymatic reaction."}
{"id": "PMID:234441", "title": "Resolution and reconstitution of Rhodospirillum rubrum pyridine dinucleotide transhydrogenase. Proteolytic and thermal inactivation of the membrane component.", "content": "Pyridine dinucleotide transhydrogenase of the Rhodospirillum rubrum chromatophore membrane was readily resolved by a washing procedure into two inactive components, a soluble transhydrogenase factor protein and an insoluble membrane-bound factor. Transhydrogenation was reconstituted on reassociation of these components. The capacity of the membrane factor to reconstitute enzymatic activity was lost after proteolysis of soluble transhydrogenase factor-depleted membranes with trypsin. NADP+ or NADPH, but neither NAD+ nor NADH, stimulated by several fold the rate of trypsin-dependent inactivation of the membrane factor. Substantial protection of the membrane factor from proteolytic inactivation was observed in the presence of Mg2+ ions, an inhibitor of transhydrogenation, or when the soluble transhydrogenase factor was bound to the membrane. Coincident with the loss of enzymatic reconstitutive capacity of the membrane factor was a loss in the ability of the membranes to bind the soluble transhydrogenase factor in a stable complex. The membrane component was inactivated by preincubating soluble transhydrogenase factor-depleted membranes at temperatures above 45 degrees. NADP+, NADPH, or Mg2+ ions, but neither NAD+ nor NADH, protected against inactivation. These studies indicate that (a) the binding of NADP+ or NADPH to the membrane factor promotes a conformational alteration in the protein such that its themostability and susceptibility to proteolysis are increased, and (b) the inhibitory Mg2+ ion-binding site resides in the membrane component.", "contents": "Resolution and reconstitution of Rhodospirillum rubrum pyridine dinucleotide transhydrogenase. Proteolytic and thermal inactivation of the membrane component. Pyridine dinucleotide transhydrogenase of the Rhodospirillum rubrum chromatophore membrane was readily resolved by a washing procedure into two inactive components, a soluble transhydrogenase factor protein and an insoluble membrane-bound factor. Transhydrogenation was reconstituted on reassociation of these components. The capacity of the membrane factor to reconstitute enzymatic activity was lost after proteolysis of soluble transhydrogenase factor-depleted membranes with trypsin. NADP+ or NADPH, but neither NAD+ nor NADH, stimulated by several fold the rate of trypsin-dependent inactivation of the membrane factor. Substantial protection of the membrane factor from proteolytic inactivation was observed in the presence of Mg2+ ions, an inhibitor of transhydrogenation, or when the soluble transhydrogenase factor was bound to the membrane. Coincident with the loss of enzymatic reconstitutive capacity of the membrane factor was a loss in the ability of the membranes to bind the soluble transhydrogenase factor in a stable complex. The membrane component was inactivated by preincubating soluble transhydrogenase factor-depleted membranes at temperatures above 45 degrees. NADP+, NADPH, or Mg2+ ions, but neither NAD+ nor NADH, protected against inactivation. These studies indicate that (a) the binding of NADP+ or NADPH to the membrane factor promotes a conformational alteration in the protein such that its themostability and susceptibility to proteolysis are increased, and (b) the inhibitory Mg2+ ion-binding site resides in the membrane component."}
{"id": "PMID:234442", "title": "Prenyltransferase from Saccharomyces cerevisiae. Purification to homogeneity and molecular properties.", "content": "Prenyltransferase (EC 2.5.1.1) has been purified to homogeneity from the supernatant fraction of yeast by ammonium sulfate fractionation, diethylaminoethyl-cellulose and hydroxylapatite chromatography, and column isoelectric focusing techniques. The active enzyme from isoelectric focusing columns emerged as a single symmetrical peak with specific activities 15- to 35-fold higher than previously reported preparations. The enzyme was found to be homogeneous by continuous polyacrylamide gel electrophoresis at pH 8.4 and discontinuous polyacrylamide gel electrophoresis at pH 6.9 as well as sodium dodecyl sulfate polyacrylamide electrophoresis at pH 7.0. By means of gel chromatography and sodium dodecyl sulfate polyacrylamide gel electrophoresis, the protein was shown to be a dimer with a molecular weight of 84,000 plus or minus 10%. The isoelectric point of the enzyme was determined to be 5.3. The enzyme synthesizes farnesyl and geranylgeranyl pyrophosphates from dimethylallyl, geranyl, and farnesyl pyrophosphates. Michaelis constants for the enzyme were 4, 8, and 14 mu M for isopentenyl, dimethylallyl, and geranyl pyrophosphates, respectively.", "contents": "Prenyltransferase from Saccharomyces cerevisiae. Purification to homogeneity and molecular properties. Prenyltransferase (EC 2.5.1.1) has been purified to homogeneity from the supernatant fraction of yeast by ammonium sulfate fractionation, diethylaminoethyl-cellulose and hydroxylapatite chromatography, and column isoelectric focusing techniques. The active enzyme from isoelectric focusing columns emerged as a single symmetrical peak with specific activities 15- to 35-fold higher than previously reported preparations. The enzyme was found to be homogeneous by continuous polyacrylamide gel electrophoresis at pH 8.4 and discontinuous polyacrylamide gel electrophoresis at pH 6.9 as well as sodium dodecyl sulfate polyacrylamide electrophoresis at pH 7.0. By means of gel chromatography and sodium dodecyl sulfate polyacrylamide gel electrophoresis, the protein was shown to be a dimer with a molecular weight of 84,000 plus or minus 10%. The isoelectric point of the enzyme was determined to be 5.3. The enzyme synthesizes farnesyl and geranylgeranyl pyrophosphates from dimethylallyl, geranyl, and farnesyl pyrophosphates. Michaelis constants for the enzyme were 4, 8, and 14 mu M for isopentenyl, dimethylallyl, and geranyl pyrophosphates, respectively."}
{"id": "PMID:234443", "title": "Purification of Keratan Sulfate-endogalactosidase and its action on keratan sulfates of different origin.", "content": "A glycosidase which attacks corneal keratan sulfate was purified from extracts of Pseudomonas sp. IFO-13309. When corneal keratan sulfate was degraded by the purified enzyme, Sephadex G-50 chromatography indicated the presence of a number of oligosaccharides differing in size and sulfate content. The characterization of two major fractions of the oligosaccharides indicated that the point of enzyme attack is limited to the endo-beta-D-galactoside bonds in which nonsulfated D-galactose residues participate. The enzyme, unlike ordinary exo-beta-D-galactosidases, did not catalyze the hydrolysis of phenyl beta-D-galactoside. Moreover, beta-D-galactosyl-(1 leads to 3)-2-acetamido-2-deoxy-beta-D-glucosyl-(1 leads to 3)-beta-D-galactosyl-(1 leads to 4)-D-glucose (\"lacto-N-tetraose\") was completely refractory to the action of this enzyme, suggesting that a structure of the type, X-(1 leads to 3)-beta-D-galactosyl-(1 leads to 4)-Y, is not the only specificity-determining factor, i.e. neighboring sugars, X and Y, or even larger portions of substrate molecule must have an important effect. Compared with corneal keratan sulfate, keratan sulfates from human nucleus pulposus and shark cartilage were attacked at lower rates with a resultant production of oligosaccharides of relatively large size. The result is in agreement with the view that considerable variations exist in the structure of keratan sulfates of different origin, and further suggests that the enzyme may serve as a useful reagent in studying these variations.", "contents": "Purification of Keratan Sulfate-endogalactosidase and its action on keratan sulfates of different origin. A glycosidase which attacks corneal keratan sulfate was purified from extracts of Pseudomonas sp. IFO-13309. When corneal keratan sulfate was degraded by the purified enzyme, Sephadex G-50 chromatography indicated the presence of a number of oligosaccharides differing in size and sulfate content. The characterization of two major fractions of the oligosaccharides indicated that the point of enzyme attack is limited to the endo-beta-D-galactoside bonds in which nonsulfated D-galactose residues participate. The enzyme, unlike ordinary exo-beta-D-galactosidases, did not catalyze the hydrolysis of phenyl beta-D-galactoside. Moreover, beta-D-galactosyl-(1 leads to 3)-2-acetamido-2-deoxy-beta-D-glucosyl-(1 leads to 3)-beta-D-galactosyl-(1 leads to 4)-D-glucose (\"lacto-N-tetraose\") was completely refractory to the action of this enzyme, suggesting that a structure of the type, X-(1 leads to 3)-beta-D-galactosyl-(1 leads to 4)-Y, is not the only specificity-determining factor, i.e. neighboring sugars, X and Y, or even larger portions of substrate molecule must have an important effect. Compared with corneal keratan sulfate, keratan sulfates from human nucleus pulposus and shark cartilage were attacked at lower rates with a resultant production of oligosaccharides of relatively large size. The result is in agreement with the view that considerable variations exist in the structure of keratan sulfates of different origin, and further suggests that the enzyme may serve as a useful reagent in studying these variations."}
{"id": "PMID:234444", "title": "Conformation and spin state in methemoglobin.", "content": "The properties of human methemoglobin have been investigated under a wide variety of conditions to determine its conformation and to test for evidence of the T state conformation which has been proposed by Perutz to exist in the presence of high spin ligands and inositol hexaphosphate (IHP). Subunit dissociation was measured as a criterion for the T state since marked differences in the tetramer-dimer equilibrium exist for oxyhemoglobin (R state) and deoxyhemoglobin (T state). In the absence of IHP, complexes of methemoglobin with both high spin ligands (water, fluoride) or low spin ligands (azide, cyanide) show extensive dissociation in 2,2-bis(hydroxymethyl)-2,2',2\"-nitriloethanol buffers, pH 6, 0.1 M NaCl, with values of the tetramer-dimer dissociation constant (K4,2) near 10-5 M. The addition of IHP lowers K4,2 to a value near 10-5 M for all forms of methemoglobin. Combination of IHP with methemoglobin promotes a conformational change, but the change is apparently independence of spin state. The conformation acquired in the presence of IHP is not identical with the T state (K4,2 similar to 10-12 M) and can also occur with hemoglobin in the ferrous form, as revealed by a substantial reduction in K4,2 for CO-hemoglobin upon addition of IHP. Subunit dissociation has also been measured using the haptoglobin reaction, since haptoglobin binds only to hemoglobin dimers. The haptoglobin experiments give results that are qualitatively in agreement with the conclusions reached by ultracentrifuge measurements. Similar results are also obtained by estimating the degree of dissociation on the basis of the material which aggregates following mixing with dithionite. The effect of IHP on azide-binding kinetics with methemoglobin has also been examined. Changes in reactivity is observed upon addition of IHP, but the principal effect is observed upon addition of IHP, but the principal effect is an enhancement of the rate of reaction of the beta chains. Changes in the reactivity of the beta93 sulfhydryl group of methemoglobin also accompany addition of IHP, but in a manner which is largely independent of the spin state of the iron. Similar changes are again found with CO-hemoglobin upon addition of IHP. The rate of binding of bromthymol blue also shows some changes upon addition of IHP, but the changes are more pronounced for deoxyhemoglobin than for methemoglobin. Since the results obtained did not appear to indicate a significant role for spin state in the changes observed, additional studies were undertaken using EPR spectroscopy.", "contents": "Conformation and spin state in methemoglobin. The properties of human methemoglobin have been investigated under a wide variety of conditions to determine its conformation and to test for evidence of the T state conformation which has been proposed by Perutz to exist in the presence of high spin ligands and inositol hexaphosphate (IHP). Subunit dissociation was measured as a criterion for the T state since marked differences in the tetramer-dimer equilibrium exist for oxyhemoglobin (R state) and deoxyhemoglobin (T state). In the absence of IHP, complexes of methemoglobin with both high spin ligands (water, fluoride) or low spin ligands (azide, cyanide) show extensive dissociation in 2,2-bis(hydroxymethyl)-2,2',2\"-nitriloethanol buffers, pH 6, 0.1 M NaCl, with values of the tetramer-dimer dissociation constant (K4,2) near 10-5 M. The addition of IHP lowers K4,2 to a value near 10-5 M for all forms of methemoglobin. Combination of IHP with methemoglobin promotes a conformational change, but the change is apparently independence of spin state. The conformation acquired in the presence of IHP is not identical with the T state (K4,2 similar to 10-12 M) and can also occur with hemoglobin in the ferrous form, as revealed by a substantial reduction in K4,2 for CO-hemoglobin upon addition of IHP. Subunit dissociation has also been measured using the haptoglobin reaction, since haptoglobin binds only to hemoglobin dimers. The haptoglobin experiments give results that are qualitatively in agreement with the conclusions reached by ultracentrifuge measurements. Similar results are also obtained by estimating the degree of dissociation on the basis of the material which aggregates following mixing with dithionite. The effect of IHP on azide-binding kinetics with methemoglobin has also been examined. Changes in reactivity is observed upon addition of IHP, but the principal effect is observed upon addition of IHP, but the principal effect is an enhancement of the rate of reaction of the beta chains. Changes in the reactivity of the beta93 sulfhydryl group of methemoglobin also accompany addition of IHP, but in a manner which is largely independent of the spin state of the iron. Similar changes are again found with CO-hemoglobin upon addition of IHP. The rate of binding of bromthymol blue also shows some changes upon addition of IHP, but the changes are more pronounced for deoxyhemoglobin than for methemoglobin. Since the results obtained did not appear to indicate a significant role for spin state in the changes observed, additional studies were undertaken using EPR spectroscopy."}
{"id": "PMID:234445", "title": "The effect of functional differences in the alpha and beta chains on the cooperativity of the osidation reduction reaction of hemoglobin.", "content": "Partially oxidized solutions of hemoglobin have been reacted with azide to determine the extent of oxidation, of the alpha and beta chains according to the method of McQuarrie and Gibson  (J. Biol. Chem. (1971) 246, 517-522) In 2, 2'2'' nitriloethanol buffer the fraction of oxidized material represented by the beta chains decreases with  decreasing extent of total oxidation, of the alpha chains. Upon addition of insitol hexaphosphate, the degree of perferntial oxidation in terms of a two-state model similar to the description of oxygenation by Edelstein (nature(1971) 230, 224-227) but with the incorporation of chain heterogeneity. The results indicate that the pH-dependent cooperativity of the oxidation-reduction reaction can be described in terms of a bell curbe of n versus log l, the allosteric somewhat lower and shifted slightly to the left, due in part to an affnity of beta chains for electrons approximately twince that of alpha chains. Because the curve is shifted to the left, oxidation-reduction equilibria at l values corresponding to pH 6 to  lie on the right side of the bell curve where cooperativity the preferntial affity of beta chains for electrons rises to about 4 times that of alpha chains. As a consequence, the coreesponding bell curve is lowered with the Hill coeficient falling to unity or below in the range of l encountered. Thus the principal cause of decreased cooperativity is chain heterogeneity and not stabilization in the t state as suggested by Perutz; under these conditions the molecules of methemoglobin in the t state are only a fractional part of the population.", "contents": "The effect of functional differences in the alpha and beta chains on the cooperativity of the osidation reduction reaction of hemoglobin. Partially oxidized solutions of hemoglobin have been reacted with azide to determine the extent of oxidation, of the alpha and beta chains according to the method of McQuarrie and Gibson  (J. Biol. Chem. (1971) 246, 517-522) In 2, 2'2'' nitriloethanol buffer the fraction of oxidized material represented by the beta chains decreases with  decreasing extent of total oxidation, of the alpha chains. Upon addition of insitol hexaphosphate, the degree of perferntial oxidation in terms of a two-state model similar to the description of oxygenation by Edelstein (nature(1971) 230, 224-227) but with the incorporation of chain heterogeneity. The results indicate that the pH-dependent cooperativity of the oxidation-reduction reaction can be described in terms of a bell curbe of n versus log l, the allosteric somewhat lower and shifted slightly to the left, due in part to an affnity of beta chains for electrons approximately twince that of alpha chains. Because the curve is shifted to the left, oxidation-reduction equilibria at l values corresponding to pH 6 to  lie on the right side of the bell curve where cooperativity the preferntial affity of beta chains for electrons rises to about 4 times that of alpha chains. As a consequence, the coreesponding bell curve is lowered with the Hill coeficient falling to unity or below in the range of l encountered. Thus the principal cause of decreased cooperativity is chain heterogeneity and not stabilization in the t state as suggested by Perutz; under these conditions the molecules of methemoglobin in the t state are only a fractional part of the population."}
{"id": "PMID:234446", "title": "The dephosphorylation of phosphoglucomutase by nucleophilic reagents.", "content": "The phosphoryl group on the serine residue at the active site of phosphoglucomutase is presumed to undergo nucleophilic attack by the monophosphate substrates glucose 1- and glucose 6-phosphate to form glucose 1,6-diphosphate. Fluoride, hydroxylamine, and several thiol compounds have now been shown to serve as effective nucleophiles toward the active phosphate and result in the dephosphorylation of phosphoglucomutase. The more extensively studied nucleophiles, cysteine, hydroxylamine, and fluoride, are effective at a concentration as low as 1 mM with a relative reactivity of 40, 2, and 1, respectively. The reaction proceeds as long as the catalytic activity of the enzyme is maintained. Inactivation of the enzyme abolishes dephosphorylation by all nucleophilic reagents thus far studied. The dephosphorylation reaction shows optimal activity of pH 6.5. The rate of dephosphorylation exhibits saturation kinetics. With fluoride the Km is 534 mM. Dephosphorylation by fluoride is stimulated by some but not all bivalent cations. Cu+ and Co2+ are the most effective. Cu2+ not only augments the reaction with fluoride but also facilitates a nucleophilic attack by water, in the absence of the halogen, to yield inorganic phosphate. No augmentation of the rate of dephosphorylation by bivalent cations can be elicited with either cysteine or hydroxylamine. The products of the fluoride reaction are phosphorofluoridate, a small but variable amount of inorganic phosphate, and a fully active dephosphoenzyme. By constrast, cysteine and hydroxylamine yield inorganic phosphate and a partially inactive enzyme. The dephosphorylation rate varies with temperature. Arrhenius plots for the fluoride reaction reveal two distinct slopes. The heat of activation between 5-37 degrees was found to be 10.2 Cal per mol. Between 0-5 degrees, however, it was considerably greater amounting to 24.3 Cal per mol.", "contents": "The dephosphorylation of phosphoglucomutase by nucleophilic reagents. The phosphoryl group on the serine residue at the active site of phosphoglucomutase is presumed to undergo nucleophilic attack by the monophosphate substrates glucose 1- and glucose 6-phosphate to form glucose 1,6-diphosphate. Fluoride, hydroxylamine, and several thiol compounds have now been shown to serve as effective nucleophiles toward the active phosphate and result in the dephosphorylation of phosphoglucomutase. The more extensively studied nucleophiles, cysteine, hydroxylamine, and fluoride, are effective at a concentration as low as 1 mM with a relative reactivity of 40, 2, and 1, respectively. The reaction proceeds as long as the catalytic activity of the enzyme is maintained. Inactivation of the enzyme abolishes dephosphorylation by all nucleophilic reagents thus far studied. The dephosphorylation reaction shows optimal activity of pH 6.5. The rate of dephosphorylation exhibits saturation kinetics. With fluoride the Km is 534 mM. Dephosphorylation by fluoride is stimulated by some but not all bivalent cations. Cu+ and Co2+ are the most effective. Cu2+ not only augments the reaction with fluoride but also facilitates a nucleophilic attack by water, in the absence of the halogen, to yield inorganic phosphate. No augmentation of the rate of dephosphorylation by bivalent cations can be elicited with either cysteine or hydroxylamine. The products of the fluoride reaction are phosphorofluoridate, a small but variable amount of inorganic phosphate, and a fully active dephosphoenzyme. By constrast, cysteine and hydroxylamine yield inorganic phosphate and a partially inactive enzyme. The dephosphorylation rate varies with temperature. Arrhenius plots for the fluoride reaction reveal two distinct slopes. The heat of activation between 5-37 degrees was found to be 10.2 Cal per mol. Between 0-5 degrees, however, it was considerably greater amounting to 24.3 Cal per mol."}
{"id": "PMID:234447", "title": "Effects of beta-adrenergic catecholamines on potassium transport in turkey erythrocytes.", "content": "Isoproterenol stimulates cellular accumulation of cyclic adenosine 3':5'-monophosphate (cyclic AMP) and produces a 2- to 4-fold increase in bidirectional potassium fluxes in turkey erythrocytes. Ouabain, which does not alter catecholamine-stimulated cellular cyclic AMP, inhibits potassium influx by 50 to 70%, does not alter potassium outflux or isoproterenol-stimulated potassium influx, but increases isoproterenol-stimulated potassium outflux. Stimulation of potassium transport by isoproterenol can be reproduced by adding cyclic AMP to the medium and is inhibited by propranolol or dichloroisoproterenol but not by phentolamine. Theophylline at concentrations which inhibit cyclic nucleotide phosphodiesterase in isolated turkey erythrocyte plasma membranes by greater than 90%, does not augment isoproterenol stimulation of cellular cyclic AMP or of potassium transport but does potentiate stimulation of potassium influx produced by adding cyclic AMP to the medium. Isoproterenol-stimulated cellular cyclic AMP increases steadily for at least 2 hours. Potassium transport, however, increases rapidly, becomes maximal after 20 to 30 min of incubation, and thereafter decreases progressively so that after 2 hours of incubation potassium fluxes are only slightly greater than for the control. Ouabain prolongs the duration of catecholamine-stimulated potassium influx and potassium outflux, reflecting its ability to relieve the refractoriness developed by turkey erythroyctes to endogenous cyclic AMP.", "contents": "Effects of beta-adrenergic catecholamines on potassium transport in turkey erythrocytes. Isoproterenol stimulates cellular accumulation of cyclic adenosine 3':5'-monophosphate (cyclic AMP) and produces a 2- to 4-fold increase in bidirectional potassium fluxes in turkey erythrocytes. Ouabain, which does not alter catecholamine-stimulated cellular cyclic AMP, inhibits potassium influx by 50 to 70%, does not alter potassium outflux or isoproterenol-stimulated potassium influx, but increases isoproterenol-stimulated potassium outflux. Stimulation of potassium transport by isoproterenol can be reproduced by adding cyclic AMP to the medium and is inhibited by propranolol or dichloroisoproterenol but not by phentolamine. Theophylline at concentrations which inhibit cyclic nucleotide phosphodiesterase in isolated turkey erythrocyte plasma membranes by greater than 90%, does not augment isoproterenol stimulation of cellular cyclic AMP or of potassium transport but does potentiate stimulation of potassium influx produced by adding cyclic AMP to the medium. Isoproterenol-stimulated cellular cyclic AMP increases steadily for at least 2 hours. Potassium transport, however, increases rapidly, becomes maximal after 20 to 30 min of incubation, and thereafter decreases progressively so that after 2 hours of incubation potassium fluxes are only slightly greater than for the control. Ouabain prolongs the duration of catecholamine-stimulated potassium influx and potassium outflux, reflecting its ability to relieve the refractoriness developed by turkey erythroyctes to endogenous cyclic AMP."}
{"id": "PMID:234448", "title": "Lipids of bovine adrenal plasma membranes.", "content": "The lipid composition of a membrane fraction from bovine adrenal cortex was determined. This preparation has the capacity to bind adrenocorticotropic hormone and is enriched in adenylate cyclase and 5'-nucleotidase. The adrenal plasma membranes have a significantly higher lipid content (54.8%) than bovine liver plasma membranes and a surprisingly low proportion of this lipid is cholesterol (4.2%). The phospholipids comprise 76.4% of the total lipids and their composition if very similar to that of bovine liver membranes with the exception of sphingomyelin which comprises only 4.5% of the phospholipids in the adrenal preparation.", "contents": "Lipids of bovine adrenal plasma membranes. The lipid composition of a membrane fraction from bovine adrenal cortex was determined. This preparation has the capacity to bind adrenocorticotropic hormone and is enriched in adenylate cyclase and 5'-nucleotidase. The adrenal plasma membranes have a significantly higher lipid content (54.8%) than bovine liver plasma membranes and a surprisingly low proportion of this lipid is cholesterol (4.2%). The phospholipids comprise 76.4% of the total lipids and their composition if very similar to that of bovine liver membranes with the exception of sphingomyelin which comprises only 4.5% of the phospholipids in the adrenal preparation."}
{"id": "PMID:234449", "title": "The molecular dissociation of ferrihemoglobin derivatives.", "content": "Measurement of the dissociation constants of ferrihemoglobin by light scattering indicates that the quaternary structure is altered by the type of heme ligand. Fluoromethemoglobin and aquomethemoglobin, high spin derivatives with weak ligands, have tetramer-dimer dissociation constants of 80 and 50 muM, respectively. For low spin cyanmethemoglobin the dissociation constants were 1 muM (pH 6.0) and 3 muM (pH 9.0) under the general conditions of 0.1 ionic strength and 25 degrees. Of the ferrihemoglobins studied, alkaline methemoglobin (pH 9.0) has the lowest dissociation constant (0.2 muM). Dissociation constants of mixtures of alkaline and fluoromethemoglobin were significantly higher than that of the alkaline form alone. At pH 9.0 the 55 and 78% fluoride-bound derivatives had tetramer-dimer dissociation constants of 0.7 and 2 muM, respectively. The cyanmethemoglobin quaternary conformation was found to be less affected by pH than the fluoromethemoglobin and aquomethemoglobin conformations. Measurement of the dissociation constant (0.2 muM) for aquomethemoglobin-inositol hexaphosphate indicates stabilization of the tetramer by this organic phosphate. The extent of stabilization by inositol hexaphosphate does not appear to be that found for deoxyhemoglobin as suggested by Perutz (Perutz, M. F. (1972) Nature 237, 495-499) even though inducement of higher spin and iron-heme plane displacement may occur.", "contents": "The molecular dissociation of ferrihemoglobin derivatives. Measurement of the dissociation constants of ferrihemoglobin by light scattering indicates that the quaternary structure is altered by the type of heme ligand. Fluoromethemoglobin and aquomethemoglobin, high spin derivatives with weak ligands, have tetramer-dimer dissociation constants of 80 and 50 muM, respectively. For low spin cyanmethemoglobin the dissociation constants were 1 muM (pH 6.0) and 3 muM (pH 9.0) under the general conditions of 0.1 ionic strength and 25 degrees. Of the ferrihemoglobins studied, alkaline methemoglobin (pH 9.0) has the lowest dissociation constant (0.2 muM). Dissociation constants of mixtures of alkaline and fluoromethemoglobin were significantly higher than that of the alkaline form alone. At pH 9.0 the 55 and 78% fluoride-bound derivatives had tetramer-dimer dissociation constants of 0.7 and 2 muM, respectively. The cyanmethemoglobin quaternary conformation was found to be less affected by pH than the fluoromethemoglobin and aquomethemoglobin conformations. Measurement of the dissociation constant (0.2 muM) for aquomethemoglobin-inositol hexaphosphate indicates stabilization of the tetramer by this organic phosphate. The extent of stabilization by inositol hexaphosphate does not appear to be that found for deoxyhemoglobin as suggested by Perutz (Perutz, M. F. (1972) Nature 237, 495-499) even though inducement of higher spin and iron-heme plane displacement may occur."}
{"id": "PMID:234450", "title": "The enzymic conversion of protoporphyrinogen IX to protoporphyrin IX. Protoporphyrinogen oxidase activity in mitochondrial extracts of Saccharomyces cerevisiae.", "content": "The oxidation of protoporphyrinogen IX to protoporphyrin IX in yeast cells is enzyme-dependent. The enzyme, protoporphyrinogen oxidase, associated with purified mitochondria isolated from Saccharomyces cerevisiae was solubilized by sonic treatment in the presence of detergent and partially purified. The molecular weight of the enzyme was 180,000 plus or minus 18,000. The purified preparation could be stored at -20 degrees in the presence of 20% glycerol for several months without loss of activity. Enzyme activity was destroyed by heating above 40 degrees and by proteolytic digestion and irreversible inactivation occurred outside the pH range of 4.0 to 9.5. The pH optimum of the enzymic reaction was 7.45 and the value of the Michaelis constant was approximately 4.8 muM. Protoporphyrinogen oxidase did not catalyse the oxidation of coproporphyrinogen I or III or uroporphyrinogen I or III and the rate of enzymic oxidation of mesoporphyrinogen IX was less than 20% of that observed with protoporphyrinogen IX. The presence of thiol groups in the enzyme system was indicated but no metal ion or other cofactor requirement was demonstrated. Enzyme activity was insensitive to cyanide, 2,4-dinitrophenol, and azide whereas it was inhibited in the presence of Cu-2+ or Co-2+ ions, high ionic strength, heme, or hemin.", "contents": "The enzymic conversion of protoporphyrinogen IX to protoporphyrin IX. Protoporphyrinogen oxidase activity in mitochondrial extracts of Saccharomyces cerevisiae. The oxidation of protoporphyrinogen IX to protoporphyrin IX in yeast cells is enzyme-dependent. The enzyme, protoporphyrinogen oxidase, associated with purified mitochondria isolated from Saccharomyces cerevisiae was solubilized by sonic treatment in the presence of detergent and partially purified. The molecular weight of the enzyme was 180,000 plus or minus 18,000. The purified preparation could be stored at -20 degrees in the presence of 20% glycerol for several months without loss of activity. Enzyme activity was destroyed by heating above 40 degrees and by proteolytic digestion and irreversible inactivation occurred outside the pH range of 4.0 to 9.5. The pH optimum of the enzymic reaction was 7.45 and the value of the Michaelis constant was approximately 4.8 muM. Protoporphyrinogen oxidase did not catalyse the oxidation of coproporphyrinogen I or III or uroporphyrinogen I or III and the rate of enzymic oxidation of mesoporphyrinogen IX was less than 20% of that observed with protoporphyrinogen IX. The presence of thiol groups in the enzyme system was indicated but no metal ion or other cofactor requirement was demonstrated. Enzyme activity was insensitive to cyanide, 2,4-dinitrophenol, and azide whereas it was inhibited in the presence of Cu-2+ or Co-2+ ions, high ionic strength, heme, or hemin."}
{"id": "PMID:234451", "title": "Functional specificity of guanosine 3':5'-monophosphate-dependent and adenosine 3':5'-monophosphate-dependent protein kinases from silkworm.", "content": "Adenosine 3':5'-monophosphate-dependent protein kinase partially purified from silkworm pupae shows identical functional activities with those of mammalian protein kinases; the insect and mammalian kinases are completely exchangeable in the phosphorylation of muscle glycogen phosphorylase kinase and glycogen synthetase resulting in the activation and inactivation of the respective enzymes. In contrast, guanosine 3':5'-monophosphate-dependent protein kinase obtained from the same organism is totally inactive in this role and phosphorylates different, mainly seryl and some threonyl, residues of acceptor proteins. Substrates of the latter kinase intimately involved in the regulation of biological processes have remained unknown.", "contents": "Functional specificity of guanosine 3':5'-monophosphate-dependent and adenosine 3':5'-monophosphate-dependent protein kinases from silkworm. Adenosine 3':5'-monophosphate-dependent protein kinase partially purified from silkworm pupae shows identical functional activities with those of mammalian protein kinases; the insect and mammalian kinases are completely exchangeable in the phosphorylation of muscle glycogen phosphorylase kinase and glycogen synthetase resulting in the activation and inactivation of the respective enzymes. In contrast, guanosine 3':5'-monophosphate-dependent protein kinase obtained from the same organism is totally inactive in this role and phosphorylates different, mainly seryl and some threonyl, residues of acceptor proteins. Substrates of the latter kinase intimately involved in the regulation of biological processes have remained unknown."}
{"id": "PMID:234452", "title": "The effect of potassium chloride on the Bohr effect of human hemoglobin.", "content": "The normal and differential titration curves of liganded and unliganded hemoglobin were measured at various KCl concentrations (0.1 to 2.0 M). In this range of KCl concentrations, the curves for deoxyhemoglobin showed no salt-induced pK changes of titratable groups. In the same salt concentration range oxyhemoglobin showed a marked change in titration behavior which could only be accounted for by a salt-induced increase in pK of some titratable groups. These results show that the suppression of the alkaline Bohr effect by high concentrations of neutral univalent salt is not caused by a weakening of the salt bridges in deoxyhemoglobin but is due to an interaction of chloride ions with oxyhemoglobin. Measurements of the Bohr effect at various KCl concentrations showed that at low chloride ion concentration (5 times 10-3 M) the alkaline Bohr effect is smaller than at a concentration of 0.1 M. This observation indicates that at a chloride ion concentration of 0.1 M, part of the alkaline Bohr effect is due to an interaction of chloride ions with hemoglobin. Furthermore, at low concentrations of chloride ions the acid Bohr effect has almost vanished. This result suggests that part of the acid Bohr effect arises from an interaction of chloride ions with oxyhemoglobin. The dependence of the Bohr effect upon the chloride ion concentration can be explained by assuming specific binding of chloride ions to both oxy- and deoxyhemoglobin, with deoxyhemoglobin having the highest affinity.", "contents": "The effect of potassium chloride on the Bohr effect of human hemoglobin. The normal and differential titration curves of liganded and unliganded hemoglobin were measured at various KCl concentrations (0.1 to 2.0 M). In this range of KCl concentrations, the curves for deoxyhemoglobin showed no salt-induced pK changes of titratable groups. In the same salt concentration range oxyhemoglobin showed a marked change in titration behavior which could only be accounted for by a salt-induced increase in pK of some titratable groups. These results show that the suppression of the alkaline Bohr effect by high concentrations of neutral univalent salt is not caused by a weakening of the salt bridges in deoxyhemoglobin but is due to an interaction of chloride ions with oxyhemoglobin. Measurements of the Bohr effect at various KCl concentrations showed that at low chloride ion concentration (5 times 10-3 M) the alkaline Bohr effect is smaller than at a concentration of 0.1 M. This observation indicates that at a chloride ion concentration of 0.1 M, part of the alkaline Bohr effect is due to an interaction of chloride ions with hemoglobin. Furthermore, at low concentrations of chloride ions the acid Bohr effect has almost vanished. This result suggests that part of the acid Bohr effect arises from an interaction of chloride ions with oxyhemoglobin. The dependence of the Bohr effect upon the chloride ion concentration can be explained by assuming specific binding of chloride ions to both oxy- and deoxyhemoglobin, with deoxyhemoglobin having the highest affinity."}
{"id": "PMID:234453", "title": "The pH dependence of the hydrolysis of benzoyl-L-arginine ethyl ester in cooled mixed solvents.", "content": "Tables of protonic activity (paH) of a number of buffers, determined in mixed solvents and at subzero temperatures, are reported for the following media: water-1,2-propanediol, water-glycerol, and water-dimethylsulfoxide (50:50, in volume). These data with those previously reported allowed us to study enzymic reactions under these conditions. The paH dependence of the tryptic hydrolysis of benzoyl-L-arginine ethyl ester has been studied in the presence of organic solvents (methanol, ethylene glycol, 1,2-propanediol, glycerol, and dimethylsulfoxide, all 50% by volume) between 20 and -20 degrees. The results have allowed us to show the validity of our paH scales in mixed solvents. The paH profiles obtained under these conditions are similar to those observed in pure water at 20 degrees. They are shifted nevertheless by both solvent and temperature. Such shifts are interpreted in terms of the effects of solvents and temperature on pKES on the basis of the conclusions drawn from a study of the effect of these variables on small dissociable molecules. The results obtained under these conditions of solvents and temperature are consistent with the presence at the active site of the enzyme of a histidine residue, and thus provide, concerning the solvent effect, a direct verification of the method of Findlay et al. (Findlay, D., Mathias, A. P., and Rabin, B. R. (1962) Biochem. J. 85, 139-144). On the other hand, the large temperature interval provided by the low temperature procedure, allows us to vary significantly the pK of ionizable groups of the enzymes and thus makes possible their identification, on the basis of their enthalpy of ionization.", "contents": "The pH dependence of the hydrolysis of benzoyl-L-arginine ethyl ester in cooled mixed solvents. Tables of protonic activity (paH) of a number of buffers, determined in mixed solvents and at subzero temperatures, are reported for the following media: water-1,2-propanediol, water-glycerol, and water-dimethylsulfoxide (50:50, in volume). These data with those previously reported allowed us to study enzymic reactions under these conditions. The paH dependence of the tryptic hydrolysis of benzoyl-L-arginine ethyl ester has been studied in the presence of organic solvents (methanol, ethylene glycol, 1,2-propanediol, glycerol, and dimethylsulfoxide, all 50% by volume) between 20 and -20 degrees. The results have allowed us to show the validity of our paH scales in mixed solvents. The paH profiles obtained under these conditions are similar to those observed in pure water at 20 degrees. They are shifted nevertheless by both solvent and temperature. Such shifts are interpreted in terms of the effects of solvents and temperature on pKES on the basis of the conclusions drawn from a study of the effect of these variables on small dissociable molecules. The results obtained under these conditions of solvents and temperature are consistent with the presence at the active site of the enzyme of a histidine residue, and thus provide, concerning the solvent effect, a direct verification of the method of Findlay et al. (Findlay, D., Mathias, A. P., and Rabin, B. R. (1962) Biochem. J. 85, 139-144). On the other hand, the large temperature interval provided by the low temperature procedure, allows us to vary significantly the pK of ionizable groups of the enzymes and thus makes possible their identification, on the basis of their enthalpy of ionization."}
{"id": "PMID:234454", "title": "Immunochemical evidence for glutamine-mediated degradation of glutamine synthetase in cultured Chinese hamster cells.", "content": "The specific activity of glutamine synthetase in cultured Chinese hamster cells is inversely related to the concentration of glutamine in the surrounding solution. Enzyme specific activity increases 8- to 10-fold when glutamine is removed from serum-free F12 growth media. The induction of glutamine synthetase activity occurs only after glutamine removal and not after the removal of other amino acids (methionine, leucine, or isoleucine). The analysis of the glutamine-mediated decrease in glutamine synthetase activity has been simplified by the finding that depression proceeds in nutrient-free buffered saline solution (141 mM NaCl, 5.4 mM KCl and 30 mM Tricine (pH 7.4). Under these conditions, 0.1 mM cyanide blocks glutamine-mediated depression. The cyanide inhibition is reversed by the addition of 1.0 mM glucose which suggests that ATP is required for depression. Glutamine-mediated depression is temperature-dependent, occurring between 25 and 45 degrees with an optimum rate at 37 degrees. Studies of the time course of induction and depression as a function of glutamine concentration suggest that glutamine regulates the rate at which the enzyme is either modified or degraded. We have employed an antibody prepared against homogeneous Chinese hamster liver glutamine synthetase to measure the amount of glutamine synthetase protein in extracts of cells containing induced or depressed levels of enzyme activity. A highly sensitive immunoprecipitation procedure enables quantitation of nanogram amounts of glutamine synthetase protein. Glutamine synthetase in cell extracts containing induced levels of enzyme activity possesses the same molecular specific activity (ratio of activity to antigenicity) as homogeneous Chinese hamster liver glutamine synthetase. The molecular specific activity of glutamine synthetase is almost the same in extracts of cells with depressed levels of enzyme obtained by growth for short (2 hours) and long (24 hours) times in the presence of glutamine. These data suggest that glutamine-mediated depression of glutamine synthetase results from degradation of enzyme molecules.", "contents": "Immunochemical evidence for glutamine-mediated degradation of glutamine synthetase in cultured Chinese hamster cells. The specific activity of glutamine synthetase in cultured Chinese hamster cells is inversely related to the concentration of glutamine in the surrounding solution. Enzyme specific activity increases 8- to 10-fold when glutamine is removed from serum-free F12 growth media. The induction of glutamine synthetase activity occurs only after glutamine removal and not after the removal of other amino acids (methionine, leucine, or isoleucine). The analysis of the glutamine-mediated decrease in glutamine synthetase activity has been simplified by the finding that depression proceeds in nutrient-free buffered saline solution (141 mM NaCl, 5.4 mM KCl and 30 mM Tricine (pH 7.4). Under these conditions, 0.1 mM cyanide blocks glutamine-mediated depression. The cyanide inhibition is reversed by the addition of 1.0 mM glucose which suggests that ATP is required for depression. Glutamine-mediated depression is temperature-dependent, occurring between 25 and 45 degrees with an optimum rate at 37 degrees. Studies of the time course of induction and depression as a function of glutamine concentration suggest that glutamine regulates the rate at which the enzyme is either modified or degraded. We have employed an antibody prepared against homogeneous Chinese hamster liver glutamine synthetase to measure the amount of glutamine synthetase protein in extracts of cells containing induced or depressed levels of enzyme activity. A highly sensitive immunoprecipitation procedure enables quantitation of nanogram amounts of glutamine synthetase protein. Glutamine synthetase in cell extracts containing induced levels of enzyme activity possesses the same molecular specific activity (ratio of activity to antigenicity) as homogeneous Chinese hamster liver glutamine synthetase. The molecular specific activity of glutamine synthetase is almost the same in extracts of cells with depressed levels of enzyme obtained by growth for short (2 hours) and long (24 hours) times in the presence of glutamine. These data suggest that glutamine-mediated depression of glutamine synthetase results from degradation of enzyme molecules."}
{"id": "PMID:234455", "title": "Ligand binding properties of hemoglobin 3 of the trout, Salmo gairdneri. The occurrence of an acid Bohr effect in the absence of heme-heme interaction.", "content": "The four components of hemoglobin from the rainbow trout (Salmo gairdneri) have been isolated. The oxygen affinities of the first two components eluted from the DEAE-cellulose column have much smaller pH dependencies than the last two components. These components have very low O2 affinities at low pH. The effect of pH on the equilibrium and kinetics of ligand binding to the third fraction, the pH-dependent component present in greatest amounts, has been studied. Measurements of ligand binding equilibria demonstrate the presence of both an alkaline and an acid Bohr effect. In the region of the alkaline Bohr effect the value of n in the Hill equation is a function of ligand affinity. For CO binding n decreases as the pH is decreased until at pH 6, the minimum ligand affinity is reached. At this pH there is also a complete loss of cooperative ligand binding. Decreasing the pH further results in an increase of ligand affinity, but this acid Bohr effect is not associated with a reappearance of cooperativity. This suggests that Fraction 3 of S. gairdneri is frozen in the low affinity, deoxygenated conformation at low pH and that the quaternary structure does not change even when fully liganded. However, the properties of the low affinity conformation of this hemoglobin are pH-dependent.", "contents": "Ligand binding properties of hemoglobin 3 of the trout, Salmo gairdneri. The occurrence of an acid Bohr effect in the absence of heme-heme interaction. The four components of hemoglobin from the rainbow trout (Salmo gairdneri) have been isolated. The oxygen affinities of the first two components eluted from the DEAE-cellulose column have much smaller pH dependencies than the last two components. These components have very low O2 affinities at low pH. The effect of pH on the equilibrium and kinetics of ligand binding to the third fraction, the pH-dependent component present in greatest amounts, has been studied. Measurements of ligand binding equilibria demonstrate the presence of both an alkaline and an acid Bohr effect. In the region of the alkaline Bohr effect the value of n in the Hill equation is a function of ligand affinity. For CO binding n decreases as the pH is decreased until at pH 6, the minimum ligand affinity is reached. At this pH there is also a complete loss of cooperative ligand binding. Decreasing the pH further results in an increase of ligand affinity, but this acid Bohr effect is not associated with a reappearance of cooperativity. This suggests that Fraction 3 of S. gairdneri is frozen in the low affinity, deoxygenated conformation at low pH and that the quaternary structure does not change even when fully liganded. However, the properties of the low affinity conformation of this hemoglobin are pH-dependent."}
{"id": "PMID:234456", "title": "Cross-linking of the components of lactose synthetase with dimethylpimelimidate.", "content": "The cross-linking of the two components of lactose synthetase, alpha-lactalbumin and a galactosyltransferase, with dimethylpimelimidate was examined. The extent of the cross-linking at pH 8.1 was found to be dependent upon the presence of substrates or inhibitors for the galactosyltransferase. N-acetylglucosamine and mixtures of either N-acetylglucosamine, Mn-2+ and UDP, or UDP-galactose and Mn-2+ promoted the formation of cross-linked species. Glucose or a mixture of UDP and Mn-2+ were much less effective in promoting cross-linking. Two types of intermolecularly cross-linked species of alpha-lactalbumin and the galactosyltransferase were obtained. Each was a 1:1 cross-linked complex of alpha-lactalbumin and either of the two forms of the transferase with molecular weights of about 42,000 and 48,000, respectively. Cross-linked complexes were not observed with more than 1 molecule each of alpha-lactalbumin and the transferase. The cross-linked complexes were obtained in homogeneous form by gel filtration on Sephadex and absorption of uncross-linked enzyme by affinity chromatography on alpha-lactalbumin-Sepharose in the presence of N-acetylglucosamine. They migrated on gel electrophoresis in sodium dodecyl sulfate with mobilities in accord with their predicted molecular weights as 1:1 complexes of alpha-lactalbumin and the transferase. The amino acid composition of the cross-linked complex was in reasonable agreement with the expected composition of a 1:1 mixture of alpha-lactalbumin and galactosyltransferase. The enzymic properties of the cross-linked and uncross-linked enzymes were compared. The cross-linked complex had a much higher intrinsic lactose synthetase activity than did uncross-linked enzyme although only about 1% of the potential activity of uncross-linked enzyme in the presence of optimal concentrations of alpha-lactalbumin. The lactose synthetase activity of the cross-linked complex, however, was unaffected by exogenous alpha-lactalbumin. In addition, the complex readily catalyzed the transfer of galactose from UDP-galactose to xylose in the absence of exogenous alpha-lactalbumin. The N-acetyllactosamine synthetase activity of the complex was low compared to its activity with other monosaccharides. Ovalbumin, which is a good acceptor for the uncross-linked transferase, was not an acceptor for the cross-linked complex. Kinetic studies of the complex suggest that its modified catalytic activity is not the result of the modification by dimethylpimelimidate but reflects the expected effects of  is provided, and that", "contents": "Cross-linking of the components of lactose synthetase with dimethylpimelimidate. The cross-linking of the two components of lactose synthetase, alpha-lactalbumin and a galactosyltransferase, with dimethylpimelimidate was examined. The extent of the cross-linking at pH 8.1 was found to be dependent upon the presence of substrates or inhibitors for the galactosyltransferase. N-acetylglucosamine and mixtures of either N-acetylglucosamine, Mn-2+ and UDP, or UDP-galactose and Mn-2+ promoted the formation of cross-linked species. Glucose or a mixture of UDP and Mn-2+ were much less effective in promoting cross-linking. Two types of intermolecularly cross-linked species of alpha-lactalbumin and the galactosyltransferase were obtained. Each was a 1:1 cross-linked complex of alpha-lactalbumin and either of the two forms of the transferase with molecular weights of about 42,000 and 48,000, respectively. Cross-linked complexes were not observed with more than 1 molecule each of alpha-lactalbumin and the transferase. The cross-linked complexes were obtained in homogeneous form by gel filtration on Sephadex and absorption of uncross-linked enzyme by affinity chromatography on alpha-lactalbumin-Sepharose in the presence of N-acetylglucosamine. They migrated on gel electrophoresis in sodium dodecyl sulfate with mobilities in accord with their predicted molecular weights as 1:1 complexes of alpha-lactalbumin and the transferase. The amino acid composition of the cross-linked complex was in reasonable agreement with the expected composition of a 1:1 mixture of alpha-lactalbumin and galactosyltransferase. The enzymic properties of the cross-linked and uncross-linked enzymes were compared. The cross-linked complex had a much higher intrinsic lactose synthetase activity than did uncross-linked enzyme although only about 1% of the potential activity of uncross-linked enzyme in the presence of optimal concentrations of alpha-lactalbumin. The lactose synthetase activity of the cross-linked complex, however, was unaffected by exogenous alpha-lactalbumin. In addition, the complex readily catalyzed the transfer of galactose from UDP-galactose to xylose in the absence of exogenous alpha-lactalbumin. The N-acetyllactosamine synthetase activity of the complex was low compared to its activity with other monosaccharides. Ovalbumin, which is a good acceptor for the uncross-linked transferase, was not an acceptor for the cross-linked complex. Kinetic studies of the complex suggest that its modified catalytic activity is not the result of the modification by dimethylpimelimidate but reflects the expected effects of  is provided, and that"}
{"id": "PMID:234457", "title": "Circular dichroism and absorbance properties of nitrotyrosyl chromophores in staphylococcal nuclease and in a model diketopiperazine.", "content": "An active derivative of staphylococcal nuclease, in which only tyrosine residue 115 has been nitrated with use of tetranitromethane, has been characterized using absorbance, circular dichroism, and fluorescence spectroscopy. The results show that nitrotyrosine-115 nuclease is indistinguishable from native nuclease with regard to the average secondary structure of the folded polypeptide chain, the susceptibility of the enzyme to heat denaturation, and the local tertiary structure around tryptophan residue 140. Inasmuch as optical properties of nitrotyrosine-115 nuclease from 300 to 500 nm can be unambiguously assigned to nitrotyrosine residue 115 in the active site region, this modified enzyme presents a good model system for studying the circular dichroism properties of this aromatic amino acid in a protein. The spectral properties of nitrotyrosine-115 nuclease have been compared to those of the model compounds, cyclo-(-Gly-Tyr(3NO2)-) and Tyr(3NO2). Circular dichroism spectral changes in nitrotyrosine-115 nuclease due to the binding of deoxythymidine 3',5'-diphosphate and Ca-2+ have been compared to the corresponding nitrotyrosyl-115 absorption spectral changes. This comparison shows that the circular dichroism difference spectrum exhibits an over-all change in the intensity of the observed Cotton effects, whereas the absorption difference spectrum exhibits a blue shift. This finding supports the suggestion that perturbations of aromatic amino acid chromophores in proteins due to ligand binding result in red or blue shifts in absorption difference spectra, but in over-all changes of intensity in circular dichroism difference spectra.", "contents": "Circular dichroism and absorbance properties of nitrotyrosyl chromophores in staphylococcal nuclease and in a model diketopiperazine. An active derivative of staphylococcal nuclease, in which only tyrosine residue 115 has been nitrated with use of tetranitromethane, has been characterized using absorbance, circular dichroism, and fluorescence spectroscopy. The results show that nitrotyrosine-115 nuclease is indistinguishable from native nuclease with regard to the average secondary structure of the folded polypeptide chain, the susceptibility of the enzyme to heat denaturation, and the local tertiary structure around tryptophan residue 140. Inasmuch as optical properties of nitrotyrosine-115 nuclease from 300 to 500 nm can be unambiguously assigned to nitrotyrosine residue 115 in the active site region, this modified enzyme presents a good model system for studying the circular dichroism properties of this aromatic amino acid in a protein. The spectral properties of nitrotyrosine-115 nuclease have been compared to those of the model compounds, cyclo-(-Gly-Tyr(3NO2)-) and Tyr(3NO2). Circular dichroism spectral changes in nitrotyrosine-115 nuclease due to the binding of deoxythymidine 3',5'-diphosphate and Ca-2+ have been compared to the corresponding nitrotyrosyl-115 absorption spectral changes. This comparison shows that the circular dichroism difference spectrum exhibits an over-all change in the intensity of the observed Cotton effects, whereas the absorption difference spectrum exhibits a blue shift. This finding supports the suggestion that perturbations of aromatic amino acid chromophores in proteins due to ligand binding result in red or blue shifts in absorption difference spectra, but in over-all changes of intensity in circular dichroism difference spectra."}
{"id": "PMID:234458", "title": "Circular dichroism of C3a anaphylatoxin. Effects of pH, heat, guanidinium chloride, and mercaptoethanol on conformation and function.", "content": "Circular dichroism spectra for C3a anaphylatoxins (protein fragments generated enzymatically in serum during activation of the third component of complement (C3)) from human and porcine sources were compared in the region of 190 to 250 nm. The spectra were indistinguishable in this region, although an estimated difference of approximately 20% exists between the primary structures of human and porcine C3a. Calculations indicated a total of 40 to 45% alpha helical content based on either the 208 or 222 nm extremum of the CD spectra. Addition of either mercaptoethanol or 6 M guanidinium chloride to human C3a produced a marked decrease in the mean residue ellipticity centered at 222 nm without irreversibly affecting the biological activity. Simultaneous addition of mercaptoethanol and guanidinium chloride virtually eliminated the CD contribution at 222 nm and resulted in more than 90% inactivation of the anaphylatoxin. Removal of the denaturant and reducing agent restored both the biological activity and the CD spectrum of C3a. Heat treatment or reduction and alkylation of human C3a produced biologically inactive and conformationally modified anaphylatoxin. In contrast, C3a inactivated by enzymatic removal of the COOH-terminal arginyl residue was structurally unchanged as judged by CD measurements. Consequently, it is proposed that in addition to the essential COOH-terminal arginyl residue, a highly ordered conformation is required for biological functionality of the C3a molecule.", "contents": "Circular dichroism of C3a anaphylatoxin. Effects of pH, heat, guanidinium chloride, and mercaptoethanol on conformation and function. Circular dichroism spectra for C3a anaphylatoxins (protein fragments generated enzymatically in serum during activation of the third component of complement (C3)) from human and porcine sources were compared in the region of 190 to 250 nm. The spectra were indistinguishable in this region, although an estimated difference of approximately 20% exists between the primary structures of human and porcine C3a. Calculations indicated a total of 40 to 45% alpha helical content based on either the 208 or 222 nm extremum of the CD spectra. Addition of either mercaptoethanol or 6 M guanidinium chloride to human C3a produced a marked decrease in the mean residue ellipticity centered at 222 nm without irreversibly affecting the biological activity. Simultaneous addition of mercaptoethanol and guanidinium chloride virtually eliminated the CD contribution at 222 nm and resulted in more than 90% inactivation of the anaphylatoxin. Removal of the denaturant and reducing agent restored both the biological activity and the CD spectrum of C3a. Heat treatment or reduction and alkylation of human C3a produced biologically inactive and conformationally modified anaphylatoxin. In contrast, C3a inactivated by enzymatic removal of the COOH-terminal arginyl residue was structurally unchanged as judged by CD measurements. Consequently, it is proposed that in addition to the essential COOH-terminal arginyl residue, a highly ordered conformation is required for biological functionality of the C3a molecule."}
{"id": "PMID:234459", "title": "Solubilization and partial characterization of rat liver squalene epoxidase.", "content": "The microsomal enzyme system from rat liver which catalyzes squalene epoxidation requires a supernatant protein and phospholipids (Tai, H., and Bloch, K. (1972) J. Biol. Chem. 247, 3767). It has now been found that these two cytoplasmic components can be replaced by Triton X-100. The same detergent solubilizes the microsomal squalene epoxidase and the resulting supernatant can be separated into two components, A and B, by DEAE-cellulose chromatography. Neither Fraction A nor B alone has significant squalene epoxidase activity but combining the two affords a reconstituted system 5-fold higher in specific epoxidase activity than that of the original microsomes. FAD and Triton X-100 in addition to molecular oxygen and NADPH are required in the reconstituted system. Subjecting Fraction A to a second DEAE-cellulose chromatography does not change its specific activity but lowers NADH-ferricyanide reductase activity and the protoheme content to 1/25 and 1/4, respectively. When Fraction B was chromatographed on Sephadex G-200, the specific epoxidase activity tested in the presence of Fraction A was increased 3-fold. This procedure also raised the specific activity of NADPH-cytochrome c reductase activity in Fraction B 3-fold. The reconstituted epoxidase system is not inhibited by either carbon monoxide, potassium cyanide, or o-phenanthrolien but Tiron at 1 mM was inhibitory (50%). Erythrocuprein has no effect on epoxidation. No evidence has been found for the participation of hemoproteins (P450 or cytochrome b5) in squalene epoxidation. Component B appears to be identical with the flavoprotein NADPH-cytochrome c reductase. Component A may be a flavoprotein with an easily dissociable prosthetic group.", "contents": "Solubilization and partial characterization of rat liver squalene epoxidase. The microsomal enzyme system from rat liver which catalyzes squalene epoxidation requires a supernatant protein and phospholipids (Tai, H., and Bloch, K. (1972) J. Biol. Chem. 247, 3767). It has now been found that these two cytoplasmic components can be replaced by Triton X-100. The same detergent solubilizes the microsomal squalene epoxidase and the resulting supernatant can be separated into two components, A and B, by DEAE-cellulose chromatography. Neither Fraction A nor B alone has significant squalene epoxidase activity but combining the two affords a reconstituted system 5-fold higher in specific epoxidase activity than that of the original microsomes. FAD and Triton X-100 in addition to molecular oxygen and NADPH are required in the reconstituted system. Subjecting Fraction A to a second DEAE-cellulose chromatography does not change its specific activity but lowers NADH-ferricyanide reductase activity and the protoheme content to 1/25 and 1/4, respectively. When Fraction B was chromatographed on Sephadex G-200, the specific epoxidase activity tested in the presence of Fraction A was increased 3-fold. This procedure also raised the specific activity of NADPH-cytochrome c reductase activity in Fraction B 3-fold. The reconstituted epoxidase system is not inhibited by either carbon monoxide, potassium cyanide, or o-phenanthrolien but Tiron at 1 mM was inhibitory (50%). Erythrocuprein has no effect on epoxidation. No evidence has been found for the participation of hemoproteins (P450 or cytochrome b5) in squalene epoxidation. Component B appears to be identical with the flavoprotein NADPH-cytochrome c reductase. Component A may be a flavoprotein with an easily dissociable prosthetic group."}
{"id": "PMID:234460", "title": "Studies on the mechanism of Mycobacterium smegmatis L-lactate oxidase. 5-Deazaflavin mononucleotide as a coenzyme analogue.", "content": "Apo-lactic oxidase from Mycobacterium smegmatis reconstituted with the deazaisoalloxazine analogue of FMN, 5-deazaFMN, undergoes reduction by L-lactate but not catalytic reoxidation by O2. The rate of deazaFMN-holo-enzyme reduction by substrate is 1.1 min-1. With L-[alpha-3-H]-lactate, direct tritium transfer to enzyme-bound deazaFMN occurs during reduction. No evidence for a stable covalent lactate-deazaFMN adduct has been obtained. The deaza-FMNH2-enzyme is reoxidized extremely slowly by O2, consistent with the sluggish nonenzymatic reaction of deaza-FMNH2 with oxygen. On the other hand, addition of pyruvate to the deazaFMNH2-enzyme causes rapid reoxidation, a process not detected in the absence of enzyme.", "contents": "Studies on the mechanism of Mycobacterium smegmatis L-lactate oxidase. 5-Deazaflavin mononucleotide as a coenzyme analogue. Apo-lactic oxidase from Mycobacterium smegmatis reconstituted with the deazaisoalloxazine analogue of FMN, 5-deazaFMN, undergoes reduction by L-lactate but not catalytic reoxidation by O2. The rate of deazaFMN-holo-enzyme reduction by substrate is 1.1 min-1. With L-[alpha-3-H]-lactate, direct tritium transfer to enzyme-bound deazaFMN occurs during reduction. No evidence for a stable covalent lactate-deazaFMN adduct has been obtained. The deaza-FMNH2-enzyme is reoxidized extremely slowly by O2, consistent with the sluggish nonenzymatic reaction of deaza-FMNH2 with oxygen. On the other hand, addition of pyruvate to the deazaFMNH2-enzyme causes rapid reoxidation, a process not detected in the absence of enzyme."}
{"id": "PMID:234461", "title": "Acetylation of amino groups and its effect on the conformation and immunological activity of obalbumin.", "content": "A procedure is described for the specific acetylation of the lysine residues of ovalbumin. Six acetylated ovalbumins varying in the degree of modification from 21 to 98% were prepared and were found to be homogeneous by polyacrylamide gel electrophoresis, immunodiffusion, and immunoelectrophresis. As expected, the anodic movement of ovalbumin increased and the isoionic point shifted to lower pH values with progressive acetylation of the protein. Measurements on ultraviolet absorption, fluorescence, tryptic digestion, intrinsic viscosity, gel filtration behavior, and immunological reactivity demonstrated that the native folded conformation of ovalbumin was appreciably altered by acetylation. However, even the maximally modified ovalbumin retained considerable residual structure consisting of regions of ordered structure containing antigenic determinants.", "contents": "Acetylation of amino groups and its effect on the conformation and immunological activity of obalbumin. A procedure is described for the specific acetylation of the lysine residues of ovalbumin. Six acetylated ovalbumins varying in the degree of modification from 21 to 98% were prepared and were found to be homogeneous by polyacrylamide gel electrophoresis, immunodiffusion, and immunoelectrophresis. As expected, the anodic movement of ovalbumin increased and the isoionic point shifted to lower pH values with progressive acetylation of the protein. Measurements on ultraviolet absorption, fluorescence, tryptic digestion, intrinsic viscosity, gel filtration behavior, and immunological reactivity demonstrated that the native folded conformation of ovalbumin was appreciably altered by acetylation. However, even the maximally modified ovalbumin retained considerable residual structure consisting of regions of ordered structure containing antigenic determinants."}
{"id": "PMID:234462", "title": "The mechanism of end product inhibition of serine biosynthesis. V. Mechanism of serim inhibition of phosphoglycerate dehydrogenases.", "content": "The reduction of enzyme-bound DPN constitutes a half-reaction of phosphoglycerate dehydrogenase and has been investigated fluorometrically. Serine was found to inhibit the half-reaction to the same extent and with the same degree of cooperation as the steady state reaction. This finding identifies the ternary complex conversion as the point in the reaction sequence at which serine inhibition occurs. Delta H determinations for the half-reaction showed no difference whether serine was or was not present and led to the conclusion that the inhibitory effect of serine could only manifest itself through the delta S term in the expression for the formation of the activated transition state complex. DL-3-P[2-2H]glyceric acid showed no primary isotope effect in the half-reaction. This result excludes hydrogen transfer as the rate-limiting step in the half-reaction and confirms that an isomerization step, affected by serine, exists in the ternary complex conversion scheme. The deuterated 3-P-glyceric acid shows an isotope effect of 2 in the steady state reaction.", "contents": "The mechanism of end product inhibition of serine biosynthesis. V. Mechanism of serim inhibition of phosphoglycerate dehydrogenases. The reduction of enzyme-bound DPN constitutes a half-reaction of phosphoglycerate dehydrogenase and has been investigated fluorometrically. Serine was found to inhibit the half-reaction to the same extent and with the same degree of cooperation as the steady state reaction. This finding identifies the ternary complex conversion as the point in the reaction sequence at which serine inhibition occurs. Delta H determinations for the half-reaction showed no difference whether serine was or was not present and led to the conclusion that the inhibitory effect of serine could only manifest itself through the delta S term in the expression for the formation of the activated transition state complex. DL-3-P[2-2H]glyceric acid showed no primary isotope effect in the half-reaction. This result excludes hydrogen transfer as the rate-limiting step in the half-reaction and confirms that an isomerization step, affected by serine, exists in the ternary complex conversion scheme. The deuterated 3-P-glyceric acid shows an isotope effect of 2 in the steady state reaction."}
{"id": "PMID:234463", "title": "Effect of nicotinamide adenine dinucleotide on the membrane-associated reduced nicotinamide adenine dinucleotide oxidase of Mycobacterium phlei.", "content": "NAD+ had a biphasic effect on the NADH oxidase activity in electron transport particles from Mycobacterium phlei. The oxidase was inhibited competitively by NAD+ at concentrations above 0.05 mM. NAD+ in concentrations from 0.02 to 0.05 mM resulted in maximum stimulation of both NADH oxidation and oxygen uptake with concentrations of substrate both above and below the apparent K-M. Oxygen uptake and cyanide sensitivity indicated that the NAD+ stimulatory effect was linked to the terminal respiratory chain. The stimulatory effect was specific for NAD+. NAD+ was also specific in protecting the oxidase during heating at 50 degrees and against inactivation during storage at 0 degrees. NAD+ glycohydrolase did not affect stimulation nor heat protection of the NADH oxidase activity if the particles were previously preincubated with NAD+. Binding studies revealed that the particles bound approximately 3.6 pmol of [14C1NAD+ per mg of electron transport particle protein. Although bound NAD+ represented only a small fraction of the total added NAD+ necessary for maximal stimulation, removal of the apparently unbound NAD+ by Sephadex chromatography revealed that particles retained the stimulated state for at least 48 hours. Further addition of NAD+ to stimulated washed particles resulted in competitive inhibition of oxidase activity. Desensitization of the oxidase to the stimulatory effect of NAD+ was achieved by heating the particles at 50 degrees for 2 min without appreciable loss of enzymatic activity. Kinetic studies indicated that addition of NADH to electron transport particles prior to preincubation with NAD+ inhibited stimulation. In addition, NADH inhibited binding of [14C]NAD+. The utilization of artificial electron acceptors, which act as a shunt of the respiratory chain at or near the flavoprotein component, indicated that NAD+ acts as at the level of the NADH dehydrogenase at a site other than the catalytic one resulting in a conformational change which causes restoration as well as protection of oxidase activity.", "contents": "Effect of nicotinamide adenine dinucleotide on the membrane-associated reduced nicotinamide adenine dinucleotide oxidase of Mycobacterium phlei. NAD+ had a biphasic effect on the NADH oxidase activity in electron transport particles from Mycobacterium phlei. The oxidase was inhibited competitively by NAD+ at concentrations above 0.05 mM. NAD+ in concentrations from 0.02 to 0.05 mM resulted in maximum stimulation of both NADH oxidation and oxygen uptake with concentrations of substrate both above and below the apparent K-M. Oxygen uptake and cyanide sensitivity indicated that the NAD+ stimulatory effect was linked to the terminal respiratory chain. The stimulatory effect was specific for NAD+. NAD+ was also specific in protecting the oxidase during heating at 50 degrees and against inactivation during storage at 0 degrees. NAD+ glycohydrolase did not affect stimulation nor heat protection of the NADH oxidase activity if the particles were previously preincubated with NAD+. Binding studies revealed that the particles bound approximately 3.6 pmol of [14C1NAD+ per mg of electron transport particle protein. Although bound NAD+ represented only a small fraction of the total added NAD+ necessary for maximal stimulation, removal of the apparently unbound NAD+ by Sephadex chromatography revealed that particles retained the stimulated state for at least 48 hours. Further addition of NAD+ to stimulated washed particles resulted in competitive inhibition of oxidase activity. Desensitization of the oxidase to the stimulatory effect of NAD+ was achieved by heating the particles at 50 degrees for 2 min without appreciable loss of enzymatic activity. Kinetic studies indicated that addition of NADH to electron transport particles prior to preincubation with NAD+ inhibited stimulation. In addition, NADH inhibited binding of [14C]NAD+. The utilization of artificial electron acceptors, which act as a shunt of the respiratory chain at or near the flavoprotein component, indicated that NAD+ acts as at the level of the NADH dehydrogenase at a site other than the catalytic one resulting in a conformational change which causes restoration as well as protection of oxidase activity."}
{"id": "PMID:234464", "title": "Molecular weight and structure of 7 S nerve growth factor protein.", "content": "The molecular weight of 7 S nerve growth factor has been studied in the analytical ultracentrifuge between pH values 6.8 and 7.8. At pH 6.8, where no dissociation is observed, the molecular weight was found to be 137,000 plus and minus 7,000. Between pH values 7.4 and 7.8 there is some dissociation. Using the data from this study and results in the literature, a model of 7 S nerve growth factor, (alpha beta gamma)2, in reversible equilibrium with a subunit complex, (alpha beta gamma), is proposed.", "contents": "Molecular weight and structure of 7 S nerve growth factor protein. The molecular weight of 7 S nerve growth factor has been studied in the analytical ultracentrifuge between pH values 6.8 and 7.8. At pH 6.8, where no dissociation is observed, the molecular weight was found to be 137,000 plus and minus 7,000. Between pH values 7.4 and 7.8 there is some dissociation. Using the data from this study and results in the literature, a model of 7 S nerve growth factor, (alpha beta gamma)2, in reversible equilibrium with a subunit complex, (alpha beta gamma), is proposed."}
{"id": "PMID:234465", "title": "Factors affecting the reassociation and reactivation of the half-molecular weight nonidentical subunits of pigeon liver fatty acid synthetase.", "content": "The pigeon liver fatty acid synthetase complex (14 S) is dissociated in low ionic strength buffer containing dithiothreitol to form a half-molecular weight subunits (9 S) which are completely inactive for the synthesis of saturated fatty acids. The dithiothreitol-protected (reduced) subunits are rapidly reassociated and reactivated to form the active enzyme complex, not only by an increase in salt concentration but also by micromolar concentrations of NADP+ or NADPH. Increases in KCl or NADPH concentration result in an increase in the extent of reactivation (equilibrium) with no change in the over-all rate of the reaction or the half-life ofreactivation of the enzyme. The extent (equilibrium) of reactivation of the enzyme is the same in 0.2 M potassium phosphate buffer, pH 7.0; 0.2 M KCl in 5 mM Tris-35 mM glycine buffer, PH 8.3; and 50 muM NADP+ or NADPH in the Tris-glycine buffer. The extent and rate of reactivation of the enzyme is dependent not only on ionic strength and NADPH concentration, but also on pH and temperature. Reactivation with 0.2 M KCl is optimal between pH 7.3 and 8.5. At higher and lower pH values the rate and extent of reactivation are lowered. The rate and extent of reactivation are also decreased as the temperature is lowered below 10 degrees. At 0 degrees there is little reactivation of enzyme activity. However, in the presence of 0.2 M KCl containing 15 to 40% glycerol at 0 degrees, reactivation of the enzyme is about 50% complete. The rate of reactivation of enzyme in the presence of KCl or NADPH conforms to first order kinetics. This result suggests that the subunits first combine to form an inactive complex which is subsequently transformed to an enzymatically active complex. Evidence for the presence of inactive complex was obtained in experiments carried out in 0.2 M KCl at pH 6.0, and in 0.2 M KCl at pH 8.3, at both 6 and 3 degrees. Under these conditions the amount of complex observed upon ultracentrifugation was greater than expected from determinations of enzyme activity. The above findings suggest that ionic and hydrophobic interactions, and possibly the water structure surrounding the interacting sites, are of prime importance in reassociation and reactivation of enzyme. In addition, NADP+ and NADPH have very specific effects in bringing about reassociation and in maintaining the structural integrity of the multienzyme complex.", "contents": "Factors affecting the reassociation and reactivation of the half-molecular weight nonidentical subunits of pigeon liver fatty acid synthetase. The pigeon liver fatty acid synthetase complex (14 S) is dissociated in low ionic strength buffer containing dithiothreitol to form a half-molecular weight subunits (9 S) which are completely inactive for the synthesis of saturated fatty acids. The dithiothreitol-protected (reduced) subunits are rapidly reassociated and reactivated to form the active enzyme complex, not only by an increase in salt concentration but also by micromolar concentrations of NADP+ or NADPH. Increases in KCl or NADPH concentration result in an increase in the extent of reactivation (equilibrium) with no change in the over-all rate of the reaction or the half-life ofreactivation of the enzyme. The extent (equilibrium) of reactivation of the enzyme is the same in 0.2 M potassium phosphate buffer, pH 7.0; 0.2 M KCl in 5 mM Tris-35 mM glycine buffer, PH 8.3; and 50 muM NADP+ or NADPH in the Tris-glycine buffer. The extent and rate of reactivation of the enzyme is dependent not only on ionic strength and NADPH concentration, but also on pH and temperature. Reactivation with 0.2 M KCl is optimal between pH 7.3 and 8.5. At higher and lower pH values the rate and extent of reactivation are lowered. The rate and extent of reactivation are also decreased as the temperature is lowered below 10 degrees. At 0 degrees there is little reactivation of enzyme activity. However, in the presence of 0.2 M KCl containing 15 to 40% glycerol at 0 degrees, reactivation of the enzyme is about 50% complete. The rate of reactivation of enzyme in the presence of KCl or NADPH conforms to first order kinetics. This result suggests that the subunits first combine to form an inactive complex which is subsequently transformed to an enzymatically active complex. Evidence for the presence of inactive complex was obtained in experiments carried out in 0.2 M KCl at pH 6.0, and in 0.2 M KCl at pH 8.3, at both 6 and 3 degrees. Under these conditions the amount of complex observed upon ultracentrifugation was greater than expected from determinations of enzyme activity. The above findings suggest that ionic and hydrophobic interactions, and possibly the water structure surrounding the interacting sites, are of prime importance in reassociation and reactivation of enzyme. In addition, NADP+ and NADPH have very specific effects in bringing about reassociation and in maintaining the structural integrity of the multienzyme complex."}
{"id": "PMID:234466", "title": "Crystallization and some properties of chondroitinase from Arthrobacter aurescens.", "content": "A strain of Arthrobacter aurescens which secretes a large amount of chondroitinase into a culture broth, was isolated from soil. The chondroitinase was purified 380-fold over culture broth in 24% yield and crystallized. Some properties of the purified enzyme were studied and described: thermal stability (below 45 degrees), pH stability (pH 4.9 to 7.4), optimum temperature (50 degrees), and optimum pH (pH 6.0). Chrondroitin sulfate A and C, chondroitin, and hyaluronic acid were split by the enzyme but dermatan sulfate could not be. The initial rates of enzymic degradation of chondroitin sulfate C, chondroitin, and hyaluronic acid were 1.1, 1.95, and 3.2, respectively, compared to that of chondroitin sulfate A. When the enzyme was allowed to act on chondroitin sulfate A and C, the reducing power and the ultraviolet absorption at 232 nm increased proportionally to the decrease in viscosity of the substrate solution. Finally these substrates were degraded to the extent of 100% to disaccharides. By the enzyme action the main products from chondroitin sulfate A and C were deta 4,5-unsaturated disaccharides, which were identified as 2-acetamido-2-deoxy-3-O-(Beta-D-gluco-4-enepyranosyluronic acid)-4-O-sulfo-D-galactose and 2-acet-amido-2-deoxy-3-O-(Beta-D-gluco-4-enepyranosyluronic acid)-6-O-sulfo-D-galactose by paper chromatography, ultraviolet absorption spectroscophy, and infrared spectroscopy. Thus it is suggested that the chondroitinase is a chondroitin sulfate A and C lyase, one of the hyaluronate lyases (EC 4.2.99.1).", "contents": "Crystallization and some properties of chondroitinase from Arthrobacter aurescens. A strain of Arthrobacter aurescens which secretes a large amount of chondroitinase into a culture broth, was isolated from soil. The chondroitinase was purified 380-fold over culture broth in 24% yield and crystallized. Some properties of the purified enzyme were studied and described: thermal stability (below 45 degrees), pH stability (pH 4.9 to 7.4), optimum temperature (50 degrees), and optimum pH (pH 6.0). Chrondroitin sulfate A and C, chondroitin, and hyaluronic acid were split by the enzyme but dermatan sulfate could not be. The initial rates of enzymic degradation of chondroitin sulfate C, chondroitin, and hyaluronic acid were 1.1, 1.95, and 3.2, respectively, compared to that of chondroitin sulfate A. When the enzyme was allowed to act on chondroitin sulfate A and C, the reducing power and the ultraviolet absorption at 232 nm increased proportionally to the decrease in viscosity of the substrate solution. Finally these substrates were degraded to the extent of 100% to disaccharides. By the enzyme action the main products from chondroitin sulfate A and C were deta 4,5-unsaturated disaccharides, which were identified as 2-acetamido-2-deoxy-3-O-(Beta-D-gluco-4-enepyranosyluronic acid)-4-O-sulfo-D-galactose and 2-acet-amido-2-deoxy-3-O-(Beta-D-gluco-4-enepyranosyluronic acid)-6-O-sulfo-D-galactose by paper chromatography, ultraviolet absorption spectroscophy, and infrared spectroscopy. Thus it is suggested that the chondroitinase is a chondroitin sulfate A and C lyase, one of the hyaluronate lyases (EC 4.2.99.1)."}
{"id": "PMID:234467", "title": "The polyadenylate polymerases from yeast.", "content": "Poly(A) polymerase activity was first detected in yeast extracts, primarily in association with the ribosomal fraction, by Twu and Bretthauer in 1971 (Twu, J. S., and Bretthauer, RK. (1971) Biochemistry 10, 1576-1582). This activity has now been separated into three distinct enzymes by chromatography on DEAE-cellulose. Each of the three enzymes can catalyze the incorporation of adenylate residues from ATP into a polyadenylate (poly(A)) tract at the 3' terminus of a primer RNA. Enzyme I elutes at 0.07 M ammonium sulfate from the DEAE-cellulose column, utilizes the mixed polynucleotide poly(A,G,C,U) or ribosomal RNA most efficiently in vitro, and may be responsible in vivo for the initiation of the poly(A) tracts found on yeast messenger RNA. Enzyme II elutes from the column at 0.20 M ammonium sulfate, requires poly(A) itself or an RNA primer containing a 3'-oligo(A) tract, and may be responsible in the nucleus for the elongation of tracts initiated by enzyme I. Enzyme III elutes from the column at 0.56 M ammonium sulfate and is present in low amounts in nuclear extracts. It may be involved in adding poly(A) tracts to messenger RNA in mitochondria. These enzymes also have the intrinsic capacity for the incorporation of cytidylate residues from CTP, which correlates with the finding of cytidylate residues in the poly(A) tracts present in the yeast RNA which is rapidly labeled in vivo. About 75% of the total poly(A) polymerase activity of yeast is enzyme I, most of which is present in the soluble protein fraction of the whole yeast extract. About 20% of the total poly(A) polymerase is enzyme II, and 1 to 5% is enzyme III. All three of the yeast poly(A) polymerases require an RNA primer with a free 3'-hydroxyl group, show no requirement for a DNA template, require Mn-2+ for optimal activity, have pH optima of 8.5, and are inhibited by GTP, CTP, UTP, and native yeast DNA. Polymerases I and II have similar molecular weights by gel filtration.", "contents": "The polyadenylate polymerases from yeast. Poly(A) polymerase activity was first detected in yeast extracts, primarily in association with the ribosomal fraction, by Twu and Bretthauer in 1971 (Twu, J. S., and Bretthauer, RK. (1971) Biochemistry 10, 1576-1582). This activity has now been separated into three distinct enzymes by chromatography on DEAE-cellulose. Each of the three enzymes can catalyze the incorporation of adenylate residues from ATP into a polyadenylate (poly(A)) tract at the 3' terminus of a primer RNA. Enzyme I elutes at 0.07 M ammonium sulfate from the DEAE-cellulose column, utilizes the mixed polynucleotide poly(A,G,C,U) or ribosomal RNA most efficiently in vitro, and may be responsible in vivo for the initiation of the poly(A) tracts found on yeast messenger RNA. Enzyme II elutes from the column at 0.20 M ammonium sulfate, requires poly(A) itself or an RNA primer containing a 3'-oligo(A) tract, and may be responsible in the nucleus for the elongation of tracts initiated by enzyme I. Enzyme III elutes from the column at 0.56 M ammonium sulfate and is present in low amounts in nuclear extracts. It may be involved in adding poly(A) tracts to messenger RNA in mitochondria. These enzymes also have the intrinsic capacity for the incorporation of cytidylate residues from CTP, which correlates with the finding of cytidylate residues in the poly(A) tracts present in the yeast RNA which is rapidly labeled in vivo. About 75% of the total poly(A) polymerase activity of yeast is enzyme I, most of which is present in the soluble protein fraction of the whole yeast extract. About 20% of the total poly(A) polymerase is enzyme II, and 1 to 5% is enzyme III. All three of the yeast poly(A) polymerases require an RNA primer with a free 3'-hydroxyl group, show no requirement for a DNA template, require Mn-2+ for optimal activity, have pH optima of 8.5, and are inhibited by GTP, CTP, UTP, and native yeast DNA. Polymerases I and II have similar molecular weights by gel filtration."}
{"id": "PMID:234468", "title": "Intracellular localization of fructose 1,6-bisphosphate aldolase.", "content": "Submission of a rat liver homogenate made in 250 mM sucrose-1 mM EDTA to centrifugation between 9,500 times g for 10 min and 105,000 times g for 60 min results in the sedimentation of 60 to 70% of the total cellular fructose 1,6-bisphosphate aldolase (EC 4.1.2.13). Under these conditions only about one-quarter of the total triose phosphate dehydrogenase and phosphoglycerate kinase appears in the microsomal fraction. Ultrastructural immunologic localization techniques have demonstrated that the aldolase is associated with the endoplasmic reticulum, in situ. The binding of this enzyme to the membrane is sensitive to changes in pH with an optimum at 6.0, and to increasing concentrations of NaCl and fructose 1,6-bisphosphate, being about 100-fold more sensitive to the ester than to the inorganic salt.", "contents": "Intracellular localization of fructose 1,6-bisphosphate aldolase. Submission of a rat liver homogenate made in 250 mM sucrose-1 mM EDTA to centrifugation between 9,500 times g for 10 min and 105,000 times g for 60 min results in the sedimentation of 60 to 70% of the total cellular fructose 1,6-bisphosphate aldolase (EC 4.1.2.13). Under these conditions only about one-quarter of the total triose phosphate dehydrogenase and phosphoglycerate kinase appears in the microsomal fraction. Ultrastructural immunologic localization techniques have demonstrated that the aldolase is associated with the endoplasmic reticulum, in situ. The binding of this enzyme to the membrane is sensitive to changes in pH with an optimum at 6.0, and to increasing concentrations of NaCl and fructose 1,6-bisphosphate, being about 100-fold more sensitive to the ester than to the inorganic salt."}
{"id": "PMID:234469", "title": "Relationship of the light-induced proton uptake in bovine retinal outer segment fragments to triton-induced membrane disruption and to volume changes.", "content": "Light-induced proton uptake in bovine retinal outer segment (ROS) fragments was shown to be closely related to pH, salt concentration, membrane integrity, and perhaps secondarily to the volume of osmotic compartments. The principal findings were as follows: 1. As pH increased, both the discs and the plasmalemma swelled, and proton uptake markedly diminished. 2. As the discs were disrupted by increasing concentrations of Triton, proton uptake at slightly alkaline pH was supplanted by proton release. 3. Increasing the concentration of chloride salts caused increased H+ uptake roughly proportional to osmotic shrinkage of the ROS. Buffering by acetate prevented the measurement of proton uptake in the presence of acetate salts, although osmotic behavior of the ROS was similar to that observed in chloride salts. Although increasing the concentration of sucrose also resulted in osmotic shrinkage of the ROS, it was not accompanied by a systematic increase in the magnitude of proton uptake. 4. Light-induced H+ uptake was accompanied by small but reproducible changes in volume, probably of the discs. The magnitude and direction of these rapid volume changes were subject to influence by pH, solute, and other variables.", "contents": "Relationship of the light-induced proton uptake in bovine retinal outer segment fragments to triton-induced membrane disruption and to volume changes. Light-induced proton uptake in bovine retinal outer segment (ROS) fragments was shown to be closely related to pH, salt concentration, membrane integrity, and perhaps secondarily to the volume of osmotic compartments. The principal findings were as follows: 1. As pH increased, both the discs and the plasmalemma swelled, and proton uptake markedly diminished. 2. As the discs were disrupted by increasing concentrations of Triton, proton uptake at slightly alkaline pH was supplanted by proton release. 3. Increasing the concentration of chloride salts caused increased H+ uptake roughly proportional to osmotic shrinkage of the ROS. Buffering by acetate prevented the measurement of proton uptake in the presence of acetate salts, although osmotic behavior of the ROS was similar to that observed in chloride salts. Although increasing the concentration of sucrose also resulted in osmotic shrinkage of the ROS, it was not accompanied by a systematic increase in the magnitude of proton uptake. 4. Light-induced H+ uptake was accompanied by small but reproducible changes in volume, probably of the discs. The magnitude and direction of these rapid volume changes were subject to influence by pH, solute, and other variables."}
{"id": "PMID:234470", "title": "Evidence for involvement of protein kinase in the activation by adenosine 3':5'-monophosphate of brain tyrosine 3-monooxygenase.", "content": "Addition of adenosine 3':5'-monophosphate (cAMP) to high speed supernatant preparations obtained from rat brain caused a 3- to 4-fold increase in tyrosine 3-monooxygenase (tyrosine hydroxylase) activity. The tyrosine 3-monooxygenase remained in an activated state upon removal of the cAMP by passing the enzyme through a Sephadex G-25 column. Substances which inhibit cAMP-dependent protein kinase, namely, EDTA, ADP, and adenosine, and protein kinase modulator, each antagonized the activation of tyrosine 3-monooxygenase produced by cAMP. Furthermore, addition of partially purified brain cAMP-dependent protein kinase caused a several-fold increase in tyrosin 3-monooxygenase activity. The activation of tyrosine 3-monooxygenase by added cAMP and protein kinase required the presence of ATP and Mg-2+. These data suggests that the cAMP activation of tyrosine 3-monooxygenase may be mediated by a cAMP-dependent protein kinase.", "contents": "Evidence for involvement of protein kinase in the activation by adenosine 3':5'-monophosphate of brain tyrosine 3-monooxygenase. Addition of adenosine 3':5'-monophosphate (cAMP) to high speed supernatant preparations obtained from rat brain caused a 3- to 4-fold increase in tyrosine 3-monooxygenase (tyrosine hydroxylase) activity. The tyrosine 3-monooxygenase remained in an activated state upon removal of the cAMP by passing the enzyme through a Sephadex G-25 column. Substances which inhibit cAMP-dependent protein kinase, namely, EDTA, ADP, and adenosine, and protein kinase modulator, each antagonized the activation of tyrosine 3-monooxygenase produced by cAMP. Furthermore, addition of partially purified brain cAMP-dependent protein kinase caused a several-fold increase in tyrosin 3-monooxygenase activity. The activation of tyrosine 3-monooxygenase by added cAMP and protein kinase required the presence of ATP and Mg-2+. These data suggests that the cAMP activation of tyrosine 3-monooxygenase may be mediated by a cAMP-dependent protein kinase."}
{"id": "PMID:234471", "title": "Formation of adenosine triphosphate from Pi and adenosine diphosphate by purified Ca-2+-adenosine triphosphatase.", "content": "Ca-2+-ATPase purified from sarcoplasmic reticulum of rabbit muscle forms a phsophoeznyme when exposed to inorganic phosphate in the presence of Mg-2+. On addition of ADP and Ca-2+ virtually all of the phosphate bound to the enzyme is transferred to form ATP. It has been shown previously and confirmed by us that (a) the purified ATPase contains one major polypeptide and about 30% phospholipids; (b) on removal of residual detergent by passage through Sephadex the enzyme forms vesicular membranes; and (c) these vesicles are leaky and incapable of accumulating Ca-2+. Our findings therefore indicate that we have observed ATP generation from ADP and P-i without the formation of an ion gradient across a membrane. We propose that the energy derived from ion-protein interaction drives the formation of ATP.", "contents": "Formation of adenosine triphosphate from Pi and adenosine diphosphate by purified Ca-2+-adenosine triphosphatase. Ca-2+-ATPase purified from sarcoplasmic reticulum of rabbit muscle forms a phsophoeznyme when exposed to inorganic phosphate in the presence of Mg-2+. On addition of ADP and Ca-2+ virtually all of the phosphate bound to the enzyme is transferred to form ATP. It has been shown previously and confirmed by us that (a) the purified ATPase contains one major polypeptide and about 30% phospholipids; (b) on removal of residual detergent by passage through Sephadex the enzyme forms vesicular membranes; and (c) these vesicles are leaky and incapable of accumulating Ca-2+. Our findings therefore indicate that we have observed ATP generation from ADP and P-i without the formation of an ion gradient across a membrane. We propose that the energy derived from ion-protein interaction drives the formation of ATP."}
{"id": "PMID:234472", "title": "Acute respiratory failure complicating multiple fractures in the absence of fat embolism. A study of pathogenesis and treatment and a preliminary report of catheterization of the right side of the heart.", "content": "Eight patients with multiple fractures were all treated for acute respiratory failure. The investigation included catheterization of the right side of the heart, determinations of alveolar-arterial oxygen gradients and studies of serum lipid and coagulation and of water and protein balance. The magnitude of respiratory failure correlated well with the number of fractures, the duration and degree of hypotension, the quantity of fluids and blood administered for resuscitation, the magnitude and duration of positive water balance, and the degree of serum hypoalbuminemia. In three patients, the pulmonary-artery pressures were normal at the onset of respiratory failure. The essential aspects of successful therapy included the early institution of assisted ventilation and the achievement of early negative negative water balance.", "contents": "Acute respiratory failure complicating multiple fractures in the absence of fat embolism. A study of pathogenesis and treatment and a preliminary report of catheterization of the right side of the heart. Eight patients with multiple fractures were all treated for acute respiratory failure. The investigation included catheterization of the right side of the heart, determinations of alveolar-arterial oxygen gradients and studies of serum lipid and coagulation and of water and protein balance. The magnitude of respiratory failure correlated well with the number of fractures, the duration and degree of hypotension, the quantity of fluids and blood administered for resuscitation, the magnitude and duration of positive water balance, and the degree of serum hypoalbuminemia. In three patients, the pulmonary-artery pressures were normal at the onset of respiratory failure. The essential aspects of successful therapy included the early institution of assisted ventilation and the achievement of early negative negative water balance."}
{"id": "PMID:234484", "title": "Action of rennin on kappa-casein.", "content": "The action of rennin on kappa-casein was studied as a function of time using several methods to measure activity. The first indication of rennin cleavage of kappa-casein is precipitability in .1 M acetate buffer at pH 5.2 and 5 C. A longer exposure to rennin is required to alter kappa-casein so that it forms a precipitate with calcium ions and loses its ability to stabilize alpha s-casein. The least sensitive indication of rennin activity is measurement of nitrogen soluble in 2% trichloroacetic acid. Electrophoresis experiments showed that these methods detect various stages in the conversion of kappa-casein para-kappa-casein.", "contents": "Action of rennin on kappa-casein. The action of rennin on kappa-casein was studied as a function of time using several methods to measure activity. The first indication of rennin cleavage of kappa-casein is precipitability in .1 M acetate buffer at pH 5.2 and 5 C. A longer exposure to rennin is required to alter kappa-casein so that it forms a precipitate with calcium ions and loses its ability to stabilize alpha s-casein. The least sensitive indication of rennin activity is measurement of nitrogen soluble in 2% trichloroacetic acid. Electrophoresis experiments showed that these methods detect various stages in the conversion of kappa-casein para-kappa-casein."}
{"id": "PMID:234485", "title": "Physiological effects of 1,3-butanediol fed to cattle.", "content": "In four trials with growing cattle we observed effects of 1,3-butanediol on rumen fermentation end products, blood components, growth rates, feed efficiency, and body composition. Diets A and C contained 80% grain: 20% alfalfa pellets and 40% grain: 60% alfalfa pellets; in diets B and D, 1,3-butanediol replaced 4% of diets A and C. Feeding 4% 1,3-butanediol caused no significant differences in rumen pH, volatile fatty acid ratios, blood glucose, or blood ketones. Cattle fed 4% 1,3-butanediol had rates of gain and feed efficiency equivalent to and often better than cattle fed the same diet without butanediol. Body composition was not affected by feeding 4% 1,3-butanediol. Results indicate 4% 1,3-butanediol can be fed to cattle without adverse physiological effects and may improve performance. When 6% or more 1,3-butanediol was fed, blood ketones were elevated considerably, animals were hyperactive, gained less weight, and feed efficiency was lower.", "contents": "Physiological effects of 1,3-butanediol fed to cattle. In four trials with growing cattle we observed effects of 1,3-butanediol on rumen fermentation end products, blood components, growth rates, feed efficiency, and body composition. Diets A and C contained 80% grain: 20% alfalfa pellets and 40% grain: 60% alfalfa pellets; in diets B and D, 1,3-butanediol replaced 4% of diets A and C. Feeding 4% 1,3-butanediol caused no significant differences in rumen pH, volatile fatty acid ratios, blood glucose, or blood ketones. Cattle fed 4% 1,3-butanediol had rates of gain and feed efficiency equivalent to and often better than cattle fed the same diet without butanediol. Body composition was not affected by feeding 4% 1,3-butanediol. Results indicate 4% 1,3-butanediol can be fed to cattle without adverse physiological effects and may improve performance. When 6% or more 1,3-butanediol was fed, blood ketones were elevated considerably, animals were hyperactive, gained less weight, and feed efficiency was lower."}
{"id": "PMID:234486", "title": "Lipid deficient extender for bovine spermatozoa: its development and use in measuring freezing-induced lipid loss.", "content": "To facilitate the measurement of lipid losses from spermatozoa due to freezing, three low-lipid seminal extenders containing lactose, bovine serum albumin, or soybean protein were evaluated as potential cryoprotectants. All extenders were formulated to have an osmotic pressure within the range of 270 to 330 mosmol and a pH of 6.8 to 7.0. Soybean protein (Promine-D) maintained the highest post-thaw motility of spermatozoa with similar survival for spermatozoa frozen in ampules and straws. The extender derived from testing several components consisted of Tris(hydroxymethyl) aminomethane (245 mM), and citric acid monohydrate (78mM), as the buffering compounds; and fructose (69 mM), glycerol (7% vol/vol), and Promine-D (1.5% wt/vol). Post-thaw sperm motility of approximately 40% was not different from the Tris-egg yolk control. Fertility of fresh rabbit semen treated with the extender was normal. After freeze-thawing, protected spermatozoa contained more lipid (1.61 versus 1.20 mug/10-6 sperm) and lost less glutamic oxaloacetic transaminase enzyme (102 versus 108 Karmen units) than when Promine-D was not incorporated. However, even with protection by soybean protein, spermatozoa lipid content decreased from 2.43 to 1.61 mug/10-6 sperm after one freeze-thawing. The lipid status of spermatozoa frozen and thawed in conventional bull seminal extenders containing large amounts of lipids is unknown.", "contents": "Lipid deficient extender for bovine spermatozoa: its development and use in measuring freezing-induced lipid loss. To facilitate the measurement of lipid losses from spermatozoa due to freezing, three low-lipid seminal extenders containing lactose, bovine serum albumin, or soybean protein were evaluated as potential cryoprotectants. All extenders were formulated to have an osmotic pressure within the range of 270 to 330 mosmol and a pH of 6.8 to 7.0. Soybean protein (Promine-D) maintained the highest post-thaw motility of spermatozoa with similar survival for spermatozoa frozen in ampules and straws. The extender derived from testing several components consisted of Tris(hydroxymethyl) aminomethane (245 mM), and citric acid monohydrate (78mM), as the buffering compounds; and fructose (69 mM), glycerol (7% vol/vol), and Promine-D (1.5% wt/vol). Post-thaw sperm motility of approximately 40% was not different from the Tris-egg yolk control. Fertility of fresh rabbit semen treated with the extender was normal. After freeze-thawing, protected spermatozoa contained more lipid (1.61 versus 1.20 mug/10-6 sperm) and lost less glutamic oxaloacetic transaminase enzyme (102 versus 108 Karmen units) than when Promine-D was not incorporated. However, even with protection by soybean protein, spermatozoa lipid content decreased from 2.43 to 1.61 mug/10-6 sperm after one freeze-thawing. The lipid status of spermatozoa frozen and thawed in conventional bull seminal extenders containing large amounts of lipids is unknown."}
{"id": "PMID:234488", "title": "Suppression of histamine-induced pruritus by three antihistaminic drugs.", "content": "A double-blind crossover study of inhibition of histamine-induced pruritus by three commonly prescribed antihistamines was conducted on 28 normal subjects. Drugs used included diphenhydramine HCl (Benadryl), cyproheptadine (Periactin), hydroxyzine HCl (Atarax), and a lactose placebo in identical capsules. Intradermal histamine dose-response thresholds of pruritus were obtained before and after pretreatment with the three antihistamines and placebo in each subject. Analysis of data revealed a fivefold increase above baseline of the histamine dose required to produce pruritus following both cyproheptadine and placebo. This compared to a tenfold increase following diphenhydramine and a 750-fold increase following hydroxyzine HCl. The most common side effect was drowsiness, which occurred with all three drugs.", "contents": "Suppression of histamine-induced pruritus by three antihistaminic drugs. A double-blind crossover study of inhibition of histamine-induced pruritus by three commonly prescribed antihistamines was conducted on 28 normal subjects. Drugs used included diphenhydramine HCl (Benadryl), cyproheptadine (Periactin), hydroxyzine HCl (Atarax), and a lactose placebo in identical capsules. Intradermal histamine dose-response thresholds of pruritus were obtained before and after pretreatment with the three antihistamines and placebo in each subject. Analysis of data revealed a fivefold increase above baseline of the histamine dose required to produce pruritus following both cyproheptadine and placebo. This compared to a tenfold increase following diphenhydramine and a 750-fold increase following hydroxyzine HCl. The most common side effect was drowsiness, which occurred with all three drugs."}
{"id": "PMID:234489", "title": "The use of psychoactive drugs in elderly patients with psychiatric disorders: survey conducted in twelve Veterans Administration hospitals.", "content": "A survey conducted at 12 VA hospitals included the collection of detailed information on the use of psychoactive drugs in 1,276 elderly psychiatric patients. On the day of the survey, 61 per cent of the patients were receiving psychoactive drugs. Prescription practices relating to the choice of drugs, prevalence of drug use, dosage, combination drug preparations, and antiparkinson agents are discussed in terms of such factors as the patient's age and the diagnosis. Also discussed is the literature on psychoactive drugs, particularly as it pertains to elderly populations.", "contents": "The use of psychoactive drugs in elderly patients with psychiatric disorders: survey conducted in twelve Veterans Administration hospitals. A survey conducted at 12 VA hospitals included the collection of detailed information on the use of psychoactive drugs in 1,276 elderly psychiatric patients. On the day of the survey, 61 per cent of the patients were receiving psychoactive drugs. Prescription practices relating to the choice of drugs, prevalence of drug use, dosage, combination drug preparations, and antiparkinson agents are discussed in terms of such factors as the patient's age and the diagnosis. Also discussed is the literature on psychoactive drugs, particularly as it pertains to elderly populations."}
{"id": "PMID:234490", "title": "Drug therapy for cardiovascular disease in the aged.", "content": "Cardiovascular diseases and their treatment in the aged are discussed under the headings of ischemic heart disease, hypertension, cardiac failure (with special reference to the use of diuretics and digoxin), infective carditis and thyroid disorders. Advanced age modifies the approach to treatment; the choice of drugs and the dosage must be adjusted accordingly. Possible drug interactions should also be considered. A rehabilitation program is of great benefit for many elderly cardiac patients. It should be planned individually and involve psychologic and environmental factors as well as medical therapy. After successful treatment of the acute episode, even the aged patient can undertake rewarding activities in his remaining lifetime.", "contents": "Drug therapy for cardiovascular disease in the aged. Cardiovascular diseases and their treatment in the aged are discussed under the headings of ischemic heart disease, hypertension, cardiac failure (with special reference to the use of diuretics and digoxin), infective carditis and thyroid disorders. Advanced age modifies the approach to treatment; the choice of drugs and the dosage must be adjusted accordingly. Possible drug interactions should also be considered. A rehabilitation program is of great benefit for many elderly cardiac patients. It should be planned individually and involve psychologic and environmental factors as well as medical therapy. After successful treatment of the acute episode, even the aged patient can undertake rewarding activities in his remaining lifetime."}
{"id": "PMID:234494", "title": "Complement activation by interaction of polyanions and polycations. I. Heparin-protamine induced consumption of complement.", "content": "Interactions of heparin and protamine in fresh human serum, in amounts far below those required for complement depletion by either agent alone, were found to induce virtually complete depletion of total hemolytic complement activity. This depletion was dependent on time, temperature, pH, divalent cations, and serum concentration. The predominant complement component hemolytic activity depleted was C1; under appropriate reaction conditions C4 and C2 were depleted as well. Equivalent amounts of heparin along induced lesser but substantial depletion of C3-9, whereas equivalent amounts of protamine had no effect upon complement component activities. We conclude that interaction of heparin with protamine, like interaction of antibody with antigen, markedly enhances its ability to interact with the first component of complement and activate the classical complement pathway. It is suggested that complement activation by interactions between certain polyanions and polycations, like interactions between antigens and antibodies, may have a role in the initiation of inflammatory reactions.", "contents": "Complement activation by interaction of polyanions and polycations. I. Heparin-protamine induced consumption of complement. Interactions of heparin and protamine in fresh human serum, in amounts far below those required for complement depletion by either agent alone, were found to induce virtually complete depletion of total hemolytic complement activity. This depletion was dependent on time, temperature, pH, divalent cations, and serum concentration. The predominant complement component hemolytic activity depleted was C1; under appropriate reaction conditions C4 and C2 were depleted as well. Equivalent amounts of heparin along induced lesser but substantial depletion of C3-9, whereas equivalent amounts of protamine had no effect upon complement component activities. We conclude that interaction of heparin with protamine, like interaction of antibody with antigen, markedly enhances its ability to interact with the first component of complement and activate the classical complement pathway. It is suggested that complement activation by interactions between certain polyanions and polycations, like interactions between antigens and antibodies, may have a role in the initiation of inflammatory reactions."}
{"id": "PMID:234495", "title": "Rat-mouse radiation chimeras: characterization of an antibody-mediated graft-vs-host reaction.", "content": "A modification of the Jerne hemolysis-in-agar technique was used to demonstrate antibody-mediated graft-vs-host (GvH) hemolytic activity in lymphoid tissues of rat-mouse radiation chimeras. Initial foci of hemolytic activity were detected on the 3rd day in spleens of lethally x-irradiated mice infused with rat spleen cells (950 R-RSp chimeras). The peak of GvH foci response occurred near the end of the 1st week when 70% of 950 R-RSp chimera spleens examined contained an average of 18 to 21 foci per spleen. GvH hemolytic activity was also detected in mice reconstituted with rat bone marrow (950 R-RBM chimeras); however, only 40% of these chimeras contained splenic foci (nine foci per spleen) on day 8, the peak day of response. Mesenteric lymph nodes from 950 R-RSp chimeras, but not 950 R-RBM chimeras, also contained GvH hemolytic foci. Specificity experiments demonstrated that the GvH hemolytic reaction could be inhibited with rabbit anti-rat IgM serum and host (C3BF) antigenic cell fragments. Indirect (IgG) hemolytic activity was also observed in spleens of 950 R-RSp chimeras 6 to 10 days after treatment. At least 90% of indirect foci appeared coincident with direct foci. Rat IgM and IgG containing cells beneath hemolytic foci were observed by combining the fluorescent antibody and foci techniques. To determine whether the foci response reflects and in vivo sensitization of donor cells, spleen cell transfer experiments were done. The results indicate that spleen cells from 950 R-RSp chimeras were more effective in acelerating mortality and anemia and induced a higher incidence of Coomb's positive red cells in lethally irradiated isogeneic recipients than spleen cells from 950 R-RBM chimeras; spleen cells from either chimera were more effective in accelerating GvH indices than spleen and marrow cells from normal rats.", "contents": "Rat-mouse radiation chimeras: characterization of an antibody-mediated graft-vs-host reaction. A modification of the Jerne hemolysis-in-agar technique was used to demonstrate antibody-mediated graft-vs-host (GvH) hemolytic activity in lymphoid tissues of rat-mouse radiation chimeras. Initial foci of hemolytic activity were detected on the 3rd day in spleens of lethally x-irradiated mice infused with rat spleen cells (950 R-RSp chimeras). The peak of GvH foci response occurred near the end of the 1st week when 70% of 950 R-RSp chimera spleens examined contained an average of 18 to 21 foci per spleen. GvH hemolytic activity was also detected in mice reconstituted with rat bone marrow (950 R-RBM chimeras); however, only 40% of these chimeras contained splenic foci (nine foci per spleen) on day 8, the peak day of response. Mesenteric lymph nodes from 950 R-RSp chimeras, but not 950 R-RBM chimeras, also contained GvH hemolytic foci. Specificity experiments demonstrated that the GvH hemolytic reaction could be inhibited with rabbit anti-rat IgM serum and host (C3BF) antigenic cell fragments. Indirect (IgG) hemolytic activity was also observed in spleens of 950 R-RSp chimeras 6 to 10 days after treatment. At least 90% of indirect foci appeared coincident with direct foci. Rat IgM and IgG containing cells beneath hemolytic foci were observed by combining the fluorescent antibody and foci techniques. To determine whether the foci response reflects and in vivo sensitization of donor cells, spleen cell transfer experiments were done. The results indicate that spleen cells from 950 R-RSp chimeras were more effective in acelerating mortality and anemia and induced a higher incidence of Coomb's positive red cells in lethally irradiated isogeneic recipients than spleen cells from 950 R-RBM chimeras; spleen cells from either chimera were more effective in accelerating GvH indices than spleen and marrow cells from normal rats."}
{"id": "PMID:234496", "title": "Intracellular events involved in the induction of immune competence in lymphoid cells by a thymus humoral factor.", "content": "A humoral factor extracted from calf thymus (THF) restores the immunocompetence of spleen cells from neonatally thymectomized (NTx) mice to induce an in vitro graft-vs-host (GVH) response. This acquistion of immunocompetence consists of a series of biochemical events, the first of which involves an obligatory rapid increase in adenyl cyclase acitivity and in intracellular levels of cyclic AMP. Protein synthesis occurs as a further step in the events leading to induction of immunocompetence by THF and could be blocked by cycloheximide with the consequent abolishment of the immunocompetence of the lymphoid cells tested. The induction of competence by THF is accompanied by a simultaneous reduction in DNA synthesis resulting from the increase in intracellular cyclic AMP levels. These steps have been studied in the absence of antigenic stimulation which is not required for the induction of competence by THF. Spleen extracts prepared by a similar procedure as THF were found to be devoid of the properties described above.", "contents": "Intracellular events involved in the induction of immune competence in lymphoid cells by a thymus humoral factor. A humoral factor extracted from calf thymus (THF) restores the immunocompetence of spleen cells from neonatally thymectomized (NTx) mice to induce an in vitro graft-vs-host (GVH) response. This acquistion of immunocompetence consists of a series of biochemical events, the first of which involves an obligatory rapid increase in adenyl cyclase acitivity and in intracellular levels of cyclic AMP. Protein synthesis occurs as a further step in the events leading to induction of immunocompetence by THF and could be blocked by cycloheximide with the consequent abolishment of the immunocompetence of the lymphoid cells tested. The induction of competence by THF is accompanied by a simultaneous reduction in DNA synthesis resulting from the increase in intracellular cyclic AMP levels. These steps have been studied in the absence of antigenic stimulation which is not required for the induction of competence by THF. Spleen extracts prepared by a similar procedure as THF were found to be devoid of the properties described above."}
{"id": "PMID:234497", "title": "Immunopathology of mouse hepatitis virus type 3mii. effect of immunosuppression in resistant mice.", "content": "Normal adult A strain mice are resistant to MHV-3 infection. A strain mice immunosuppressed by 600 rads of x-irradiation or by anti-lymphocyte serum treatment became susceptible to the virus and died with specific lesions of the liver and high virus titers. However, mice immunized with MHV-3 before sublethal x-iraddiation resisted a second injection of virus. Resistant adult (A times C3H) F-1 hybrids undergoing graft-vs-host (GVH) reaction became highly susceptible to MHV-3 injected 8 days after parental cell injection. Virus titer 3 days after injection was 2 logs higher in mice undergoing GVH than in controls. However F-1 hybrid mice resisted virus challenge when the first injection of virus was given 2 weeks before GVH induction. In addition, thymectomy also modified the behavior of resistant animals toward virus infection. It appears, therefore, that cell-mediated immune functions play an important role in resistance of mice to MHV-3.", "contents": "Immunopathology of mouse hepatitis virus type 3mii. effect of immunosuppression in resistant mice. Normal adult A strain mice are resistant to MHV-3 infection. A strain mice immunosuppressed by 600 rads of x-irradiation or by anti-lymphocyte serum treatment became susceptible to the virus and died with specific lesions of the liver and high virus titers. However, mice immunized with MHV-3 before sublethal x-iraddiation resisted a second injection of virus. Resistant adult (A times C3H) F-1 hybrids undergoing graft-vs-host (GVH) reaction became highly susceptible to MHV-3 injected 8 days after parental cell injection. Virus titer 3 days after injection was 2 logs higher in mice undergoing GVH than in controls. However F-1 hybrid mice resisted virus challenge when the first injection of virus was given 2 weeks before GVH induction. In addition, thymectomy also modified the behavior of resistant animals toward virus infection. It appears, therefore, that cell-mediated immune functions play an important role in resistance of mice to MHV-3."}
{"id": "PMID:234498", "title": "Thyroglobulin-binding lymphoid cells in obese strain (OS) chickens.", "content": "The binding of chicken thyroglobulin-coated chicken red blood cells by splenic, thymic, and bursal lymphoid cells was analysed in Obese strain (OS) chickens with spontaneous autoimmune thyroiditis and normal white Leghorn controls aged 1 week to 2.5 yr. Chicken erythrocytes coated with pneumococcal polysaccharide SIIII served as controls. The specificity of thyroglobulin-rosette-forming cells was verified by inhibition experiments. OS chickens showed significantly higher counts of thyroglobulin-rosette-forming cells in the spleen and thymus as compared to normal controls while no such difference was found for SII-rosette-forming cells. The values obtained with bursal lymphoid cells were in the same range in both OS and normal white Leghorn birds. The appearance of thyroglobulin-rosette-forming cells and their peak values clearly preceded the maximum frequency and severity of thyroiditis and the peak of the thyroglobulin antibody curve. It is concluded that the presence of thyroglobulin rosette-forming cells is a prerequisite for the future development of spontaneous autoimmune thyroiditis in the OS. Inhibition studies with specific turkey anti-chicken bursa and thymus cell sera revealed the B cell nature of active thyroglobulin-rosette-forming cells and suggested that passive rosette-forming cells were of T cell origin.", "contents": "Thyroglobulin-binding lymphoid cells in obese strain (OS) chickens. The binding of chicken thyroglobulin-coated chicken red blood cells by splenic, thymic, and bursal lymphoid cells was analysed in Obese strain (OS) chickens with spontaneous autoimmune thyroiditis and normal white Leghorn controls aged 1 week to 2.5 yr. Chicken erythrocytes coated with pneumococcal polysaccharide SIIII served as controls. The specificity of thyroglobulin-rosette-forming cells was verified by inhibition experiments. OS chickens showed significantly higher counts of thyroglobulin-rosette-forming cells in the spleen and thymus as compared to normal controls while no such difference was found for SII-rosette-forming cells. The values obtained with bursal lymphoid cells were in the same range in both OS and normal white Leghorn birds. The appearance of thyroglobulin-rosette-forming cells and their peak values clearly preceded the maximum frequency and severity of thyroiditis and the peak of the thyroglobulin antibody curve. It is concluded that the presence of thyroglobulin rosette-forming cells is a prerequisite for the future development of spontaneous autoimmune thyroiditis in the OS. Inhibition studies with specific turkey anti-chicken bursa and thymus cell sera revealed the B cell nature of active thyroglobulin-rosette-forming cells and suggested that passive rosette-forming cells were of T cell origin."}
{"id": "PMID:234499", "title": "Platelets fixed with paraformaldehyde: a new reagent for assay of von Willebrand factor and platelet aggregating factor.", "content": "Present methods for assay of platelet aggregating agents use freshly prepared platelets. Much time is spent in daily preparation of platelets and standardization presents problems. The preparation of fixed washed platelets (FWP) and their use in two bioassays are described in this report. Washed human platelets were fixed for 48 hours with 4 per cent paraformaldehyde, washed twice in phosphate buffer, pH 6.4, and stored at 4 degrees C. Aggregation of FWP was studied with a macroscopic test and a light absorbance measurement. FWP did not aggregate with adenosine diphosphate, collagen, adrenalin, and thrombin. FWP aggregated with bovine or porcine plasma, poly-L-lysine, and ristocetin with normal human plasma but not with von Willebrand's disease plasma. These observations confirm the direct aggregating effect of these agents. Macroscopic aggregation times were dependent on the amount of aggregating agent (bovine plasma, normal human plasma). A quantitative assay for bovine platelet aggregating factor (PAF) and von Willebrand factor (vWF) with FWP was developed. The ability of FWP to aggregate remained unchanged after 1 month of storage at 4 degrees C. Ristocetin alone caused a decrease in light transmission of FWP suspensions, depending upon the concentration of ristocetin, but did not cause aggregation. FWP constitute a stable reagent suitable for quantitative measurement of PAF and vWF.", "contents": "Platelets fixed with paraformaldehyde: a new reagent for assay of von Willebrand factor and platelet aggregating factor. Present methods for assay of platelet aggregating agents use freshly prepared platelets. Much time is spent in daily preparation of platelets and standardization presents problems. The preparation of fixed washed platelets (FWP) and their use in two bioassays are described in this report. Washed human platelets were fixed for 48 hours with 4 per cent paraformaldehyde, washed twice in phosphate buffer, pH 6.4, and stored at 4 degrees C. Aggregation of FWP was studied with a macroscopic test and a light absorbance measurement. FWP did not aggregate with adenosine diphosphate, collagen, adrenalin, and thrombin. FWP aggregated with bovine or porcine plasma, poly-L-lysine, and ristocetin with normal human plasma but not with von Willebrand's disease plasma. These observations confirm the direct aggregating effect of these agents. Macroscopic aggregation times were dependent on the amount of aggregating agent (bovine plasma, normal human plasma). A quantitative assay for bovine platelet aggregating factor (PAF) and von Willebrand factor (vWF) with FWP was developed. The ability of FWP to aggregate remained unchanged after 1 month of storage at 4 degrees C. Ristocetin alone caused a decrease in light transmission of FWP suspensions, depending upon the concentration of ristocetin, but did not cause aggregation. FWP constitute a stable reagent suitable for quantitative measurement of PAF and vWF."}
{"id": "PMID:234500", "title": "Determination of hemoglobin-oxygen affinity on micro samples.", "content": "The spectrophotometric determination of hemoglobin-oxygen dissociation on dilute red cell suspensions has been modified by the use of a bicarbonate buffer containing bovine serum albumin. The red cell suspension is equillibrated with known ratios of air and nitrogen and 5 per cent carbon dioxide at atmospheric pressure using two gas pumps. The method enables the hemoglobin-oxygen dissociation curve to be measured on 10 to 20 mul of whole blood, and has given values for the P50 (the oxygen tension at 50 per cent hemoglobin-oxygen saturation) of 25.9 plus or minus  1.5 S. D. which are comparable to the value of 26.0 plus or minus 1.0 S. D. obtained by the mixing technique and by other methods. The addition of bovine albumin (35 mg. per cent or greater) increased the P50 by 3 mm. Hg above that obtained with buffer alone. The P50 value has been compared in bis-Tris and phosphate buffers with and without albumin, and in bicarbonate buffers with the addition of approximately equimolar concentrations of either human or bovine serum albumin or polyvinyl-pyrrolidone (PVP), and buffer alone. The effect of albumin on the P50 value was most marked in bicarbonate buffer, and was statistically significantly greater in the presence of human or bovine albumin than in buffer alone or buffer plus PVP. The addition of albumin could not be explained through an alteration of cell shape or volume, but may be an influence on intracellular pH.", "contents": "Determination of hemoglobin-oxygen affinity on micro samples. The spectrophotometric determination of hemoglobin-oxygen dissociation on dilute red cell suspensions has been modified by the use of a bicarbonate buffer containing bovine serum albumin. The red cell suspension is equillibrated with known ratios of air and nitrogen and 5 per cent carbon dioxide at atmospheric pressure using two gas pumps. The method enables the hemoglobin-oxygen dissociation curve to be measured on 10 to 20 mul of whole blood, and has given values for the P50 (the oxygen tension at 50 per cent hemoglobin-oxygen saturation) of 25.9 plus or minus  1.5 S. D. which are comparable to the value of 26.0 plus or minus 1.0 S. D. obtained by the mixing technique and by other methods. The addition of bovine albumin (35 mg. per cent or greater) increased the P50 by 3 mm. Hg above that obtained with buffer alone. The P50 value has been compared in bis-Tris and phosphate buffers with and without albumin, and in bicarbonate buffers with the addition of approximately equimolar concentrations of either human or bovine serum albumin or polyvinyl-pyrrolidone (PVP), and buffer alone. The effect of albumin on the P50 value was most marked in bicarbonate buffer, and was statistically significantly greater in the presence of human or bovine albumin than in buffer alone or buffer plus PVP. The addition of albumin could not be explained through an alteration of cell shape or volume, but may be an influence on intracellular pH."}
{"id": "PMID:234501", "title": "Thiol-disulfide interchange in the binding of bence jones proteins to alpha-antitrypsin, prealbumin, and albumin.", "content": "Native light Ig chains of kappa- but not of lambda-type form -S-S linked complexes with prealbumin, alpha1-AT and albumin in vivo. kappa-chains isolated from urines have cysteinyls which are more promptly reacting with dithionitrobenzoate (DTNB) than lambda-chains. Both are monomerized on this reaction. On addition to plasma mixed disulfides between both types of light chains and DTNB form larger amounts of complexes than the native chains. The lower reactivity of native lambda-chains to the plasma proteins can be explained by their higher dimer stability. From the light chain reactions obtained with isolated alpha1-AT and albumin it is concluded that alpha1-AT has a disulfide which efficiently interchanges with monomeric, light chain thiolate ions released from thionitrobenzoate derivates of light chains and that on interchange with the derivatized light chains albumin releases more free light chains into the solution than are bound to albumin. Addition of derivatized light chains to a mixture of alpha1-AT and albumin increases the yield of alpha1-AT complexes and decreases the amount of albumin complexes formed. The relative amount of the different complexes formed in the latter experiments corresponds to the findings in vivo in patients with Bence Jones proteinemia. Prealbumin and alpha1-AT in plasma have a roughly 10-fold stronger tendency to link the light chains than albumin. The complexes are formed through thiol-disulfide interchange though neither the disulfide of native alpha1-AT nor the thiols of prealbumin is available for reaction with DTNB. The three plasma proteins may together constitute a system for linkage and transport of peptides with reactive thiols or disulfides released into the extracellular fluids. The trypsin and elastase binding and inhibiting capacity of alpha1-AT remains after cleavage of the internal -S-S-bridge of alpha1-AT through interchange with a light chain thiol for which reason an intact internal -S-S-bridge of alpha1-AT is not necessary for inhibition and linkdage of the enzymes.", "contents": "Thiol-disulfide interchange in the binding of bence jones proteins to alpha-antitrypsin, prealbumin, and albumin. Native light Ig chains of kappa- but not of lambda-type form -S-S linked complexes with prealbumin, alpha1-AT and albumin in vivo. kappa-chains isolated from urines have cysteinyls which are more promptly reacting with dithionitrobenzoate (DTNB) than lambda-chains. Both are monomerized on this reaction. On addition to plasma mixed disulfides between both types of light chains and DTNB form larger amounts of complexes than the native chains. The lower reactivity of native lambda-chains to the plasma proteins can be explained by their higher dimer stability. From the light chain reactions obtained with isolated alpha1-AT and albumin it is concluded that alpha1-AT has a disulfide which efficiently interchanges with monomeric, light chain thiolate ions released from thionitrobenzoate derivates of light chains and that on interchange with the derivatized light chains albumin releases more free light chains into the solution than are bound to albumin. Addition of derivatized light chains to a mixture of alpha1-AT and albumin increases the yield of alpha1-AT complexes and decreases the amount of albumin complexes formed. The relative amount of the different complexes formed in the latter experiments corresponds to the findings in vivo in patients with Bence Jones proteinemia. Prealbumin and alpha1-AT in plasma have a roughly 10-fold stronger tendency to link the light chains than albumin. The complexes are formed through thiol-disulfide interchange though neither the disulfide of native alpha1-AT nor the thiols of prealbumin is available for reaction with DTNB. The three plasma proteins may together constitute a system for linkage and transport of peptides with reactive thiols or disulfides released into the extracellular fluids. The trypsin and elastase binding and inhibiting capacity of alpha1-AT remains after cleavage of the internal -S-S-bridge of alpha1-AT through interchange with a light chain thiol for which reason an intact internal -S-S-bridge of alpha1-AT is not necessary for inhibition and linkdage of the enzymes."}
{"id": "PMID:234502", "title": "Gas transport and blood acid-base balance in diving sea snakes.", "content": "The values of hemoglobin concentration, Hb-O2 affinity and buffering capacity of the blood of six sea snake species considerably overlap values from terrestrial squamates. Decreased blood pH had little effect on the P50 but increased the n-value of Hb-O2 equilibrium curves. The O2 saturation of blood in the dorsal aorta varied between about 30 and 70% during voluntary diving in Acalyptophis peronii and Lapemis hardwickii. Voluntary dives ended when the lung PP02 was about 50 mm Hg and the arterial PO2 about 30 mm Hg indicating that roughly half of the O2 reserves had been used. In conjunction with relatively stable blood lactate concentration and pH, this indicates that voluntary dives occurred largely aerobically. In contrast, forced dives resulted in depletion of O2 reserves and large changes in blood acid-base balance. Long recovery periods following forced dives are inconsistent with field observations and thus suggest that extensive anaerobic metabolism does not normally occur in sea snakes. Bradycardia was not evident during forced dives. Large differences in PO2 between the lung and dorsal aorta indicated considerable right to left shunting either in the heart or in the lung. Venous blood represented over 50% of the systemic flow when there was considerable O2 in the lung. Therefore blood PO2 may remain relatively low despite elevated lung PO2 resulting from diving. In view of substantial capability for extra-pulmonary gas exchange, high shunting reduces the possibility of losing O2 through the skin and also may help prevent decompression sickness following deep dives.", "contents": "Gas transport and blood acid-base balance in diving sea snakes. The values of hemoglobin concentration, Hb-O2 affinity and buffering capacity of the blood of six sea snake species considerably overlap values from terrestrial squamates. Decreased blood pH had little effect on the P50 but increased the n-value of Hb-O2 equilibrium curves. The O2 saturation of blood in the dorsal aorta varied between about 30 and 70% during voluntary diving in Acalyptophis peronii and Lapemis hardwickii. Voluntary dives ended when the lung PP02 was about 50 mm Hg and the arterial PO2 about 30 mm Hg indicating that roughly half of the O2 reserves had been used. In conjunction with relatively stable blood lactate concentration and pH, this indicates that voluntary dives occurred largely aerobically. In contrast, forced dives resulted in depletion of O2 reserves and large changes in blood acid-base balance. Long recovery periods following forced dives are inconsistent with field observations and thus suggest that extensive anaerobic metabolism does not normally occur in sea snakes. Bradycardia was not evident during forced dives. Large differences in PO2 between the lung and dorsal aorta indicated considerable right to left shunting either in the heart or in the lung. Venous blood represented over 50% of the systemic flow when there was considerable O2 in the lung. Therefore blood PO2 may remain relatively low despite elevated lung PO2 resulting from diving. In view of substantial capability for extra-pulmonary gas exchange, high shunting reduces the possibility of losing O2 through the skin and also may help prevent decompression sickness following deep dives."}
{"id": "PMID:234503", "title": "The effect of coenzyme leakage and replacement on the growth and metabolism of two fusobacteria.", "content": "Suspensions in water of two species of Fusobacterium leaked several coenzymes when incubated at normal growth temperatures. Chromatography of filtrates from these suspensions revealed the presence of NAD, NADP, FMN, tetrahydrofolic acid and, in one of the two, pyridoxal phosphate. Analyses of some enzymic activities in whole organisms demonstrated deficiencies in coenzymes:glutamate dehydrogenase was virtually inactive in the absence of added NAD; tryptophanase activities were diminished by washing but the extent differed between strains; histidase activity was not decreased by washing or suspension in water or saline. Both lag phase and doubling time increased markedly in severely washed organisms inoculated into fresh medium. Addition of appropriate coenzymes shortened the lag phase for both strains and shortened the doubling time in one.", "contents": "The effect of coenzyme leakage and replacement on the growth and metabolism of two fusobacteria. Suspensions in water of two species of Fusobacterium leaked several coenzymes when incubated at normal growth temperatures. Chromatography of filtrates from these suspensions revealed the presence of NAD, NADP, FMN, tetrahydrofolic acid and, in one of the two, pyridoxal phosphate. Analyses of some enzymic activities in whole organisms demonstrated deficiencies in coenzymes:glutamate dehydrogenase was virtually inactive in the absence of added NAD; tryptophanase activities were diminished by washing but the extent differed between strains; histidase activity was not decreased by washing or suspension in water or saline. Both lag phase and doubling time increased markedly in severely washed organisms inoculated into fresh medium. Addition of appropriate coenzymes shortened the lag phase for both strains and shortened the doubling time in one."}
{"id": "PMID:234504", "title": "Extremely thermophilic acidophilic bacteria convergent with Sulfolobus acidocaldarius.", "content": "A series of extremely thermophilic acidophilic bacteria has been characterized as closely resembling the species Sulfolobus acidocaldarius except for a totally different guanosine-cytosine content in the DNA; some conceptual consequences of this situation are discussed. Both organisms also share special features, including a very characteristic type of ether lipid, with other extreme acidophilic thermophiles.", "contents": "Extremely thermophilic acidophilic bacteria convergent with Sulfolobus acidocaldarius. A series of extremely thermophilic acidophilic bacteria has been characterized as closely resembling the species Sulfolobus acidocaldarius except for a totally different guanosine-cytosine content in the DNA; some conceptual consequences of this situation are discussed. Both organisms also share special features, including a very characteristic type of ether lipid, with other extreme acidophilic thermophiles."}
{"id": "PMID:234505", "title": "Ammonia assimilation by rhizobium cultures and bacteroids.", "content": "The enzymes involved in the assimilation of ammonia by free-living cultures of Rhizobium spp. are glutamine synthetase (EC. 6.o.I.2), glutamate synthase (L-glutamine:2-oxoglutarate amino transferase) and glutamate dehydrogenase (ED I.4.I.4). Under conditions of ammonia or nitrate limitation in a chemostat the assimilation of ammonia by cultures of R. leguminosarum, R. trifolii and R. japonicum proceeded via glutamine synthetase and glutamate synthase. Under glucose limitation and with an excess of inorganic nitrogen, ammonia was assimilated via glutamate dehydrogenase, neither glutamine synthetase nor glutamate synthase activities being detected in extracts. The coenzyme specificity of glutamate synthase varied according to species, being linked to NADP for the fast-growing R. leguminosarum, R. melitoti, R. phaseoli and R. trifolii but to NAD for the slow-growing R. japonicum and R. lupini. Glutamine synthetase, glutamate synthase and glutamate dehydrogenase activities were assayed in sonicated bacteroid preparations and in the nodule supernatants of Glycine max, Vicia faba, Pisum sativum, Lupinus luteus, Medicago sativa, Phaseolus coccineus and P. vulgaris nodules. All bacteroid preparations, except those from M. sativa and P. coccineus, contained glutamate synthase but substantial activities were found only in Glycine max and Lupinus luteus. The glutamine synthetase activities of bacteroids were low, although high activities were found in all the nodule supernatants. Glutamate dehydrogenase activity was present in all bacteroid samples examined. There was no evidence for the operation of the glutamine synthetase/glutamate synthase system in ammonia assimilation in root nodules, suggesting that ammonia produced by nitrogen fixation in the bacteroid is assimilated by enzymes of the plant system.", "contents": "Ammonia assimilation by rhizobium cultures and bacteroids. The enzymes involved in the assimilation of ammonia by free-living cultures of Rhizobium spp. are glutamine synthetase (EC. 6.o.I.2), glutamate synthase (L-glutamine:2-oxoglutarate amino transferase) and glutamate dehydrogenase (ED I.4.I.4). Under conditions of ammonia or nitrate limitation in a chemostat the assimilation of ammonia by cultures of R. leguminosarum, R. trifolii and R. japonicum proceeded via glutamine synthetase and glutamate synthase. Under glucose limitation and with an excess of inorganic nitrogen, ammonia was assimilated via glutamate dehydrogenase, neither glutamine synthetase nor glutamate synthase activities being detected in extracts. The coenzyme specificity of glutamate synthase varied according to species, being linked to NADP for the fast-growing R. leguminosarum, R. melitoti, R. phaseoli and R. trifolii but to NAD for the slow-growing R. japonicum and R. lupini. Glutamine synthetase, glutamate synthase and glutamate dehydrogenase activities were assayed in sonicated bacteroid preparations and in the nodule supernatants of Glycine max, Vicia faba, Pisum sativum, Lupinus luteus, Medicago sativa, Phaseolus coccineus and P. vulgaris nodules. All bacteroid preparations, except those from M. sativa and P. coccineus, contained glutamate synthase but substantial activities were found only in Glycine max and Lupinus luteus. The glutamine synthetase activities of bacteroids were low, although high activities were found in all the nodule supernatants. Glutamate dehydrogenase activity was present in all bacteroid samples examined. There was no evidence for the operation of the glutamine synthetase/glutamate synthase system in ammonia assimilation in root nodules, suggesting that ammonia produced by nitrogen fixation in the bacteroid is assimilated by enzymes of the plant system."}
{"id": "PMID:234506", "title": "Glucose repression of enterotoxins A, B and C and other extracellular proteins in staphlyococci in batch and continuous culture.", "content": "The production of enterotoxins, lipase and total extracellular protein by four strains of Staphylococcus aureus grown in batch culture at a controlled pH of 6.5 in a completely defined medium was markedly reduced by glucose or glycerol constantly maintained at 0.I M. A concomitant increase in the production of deoxyribonuclease, up to 13-fold, showed however that not all extracellular proteins are under the same control mechanism. The presence of glucose and glycerol in the medium also resulted in a rapid increase in the specific growth rate. However, growth of S. aureus s6 in Mgilimited continuous culture showed that glucose repression of enterotoxin B when the growth rate was held constant was more than twice that in batch culture. Therefore glucose repression can occur independently of an increase in growth rate. The specific rate of production of enterotoxin B, lipase, deoxyribonuclease, beta-haemolysin and total extracellular protein by S. aureus s6 increased as the growth rate increased from 0.07 to 0.24 h-1. Non-replicating cells grown in the absence of glucose produced considerable amounts of enterotoxin, and production was not repressed by the presence of glucose in the resuspension medium. In contrast, no enterotoxin B or C was obtained from nonreplicating cells grown in the presence of glucose. Chloramphenicol completely inhibited enterotoxin production by non-replicating cells, indicating that synthesis of new protein was required.", "contents": "Glucose repression of enterotoxins A, B and C and other extracellular proteins in staphlyococci in batch and continuous culture. The production of enterotoxins, lipase and total extracellular protein by four strains of Staphylococcus aureus grown in batch culture at a controlled pH of 6.5 in a completely defined medium was markedly reduced by glucose or glycerol constantly maintained at 0.I M. A concomitant increase in the production of deoxyribonuclease, up to 13-fold, showed however that not all extracellular proteins are under the same control mechanism. The presence of glucose and glycerol in the medium also resulted in a rapid increase in the specific growth rate. However, growth of S. aureus s6 in Mgilimited continuous culture showed that glucose repression of enterotoxin B when the growth rate was held constant was more than twice that in batch culture. Therefore glucose repression can occur independently of an increase in growth rate. The specific rate of production of enterotoxin B, lipase, deoxyribonuclease, beta-haemolysin and total extracellular protein by S. aureus s6 increased as the growth rate increased from 0.07 to 0.24 h-1. Non-replicating cells grown in the absence of glucose produced considerable amounts of enterotoxin, and production was not repressed by the presence of glucose in the resuspension medium. In contrast, no enterotoxin B or C was obtained from nonreplicating cells grown in the presence of glucose. Chloramphenicol completely inhibited enterotoxin production by non-replicating cells, indicating that synthesis of new protein was required."}
{"id": "PMID:234507", "title": "Enzyme electrophoretograms in the analysis of taxon relatedness of Micrococcus cryophilus, Branhamella catarrhalis and atypical Neisserias.", "content": "Extracts were prepared from Micrococcus cryophilus, several strains of Branhamella catarrhalis and Neisseria spp. Esterases, NADP-dependent isocitrate dehydrogenase and malate dehydrogenase activities were assayed after electrophoresis of extracts of polyacrylamide gels. Except for Neisseria perflava and N. sicca which resolved activity bands for the acetate-esterase only, the remaining bacteria exhibited species-specific esterase patterns also for the propionate and butyrate substrates. The multiple esterase patterns from B. catarrhalis ATCC25238 were qualitatively and quantitatively different from those of B. catarrhalis ATCC23246. This finding and other evidence supports a taxonomic shift of the latter to a species level of that genus. The atypical neisserias N. caviae and N. ovis appeared to exhibit an intrageneric specificity in their esterase patterns with those from B. catarrhalis but not to the other Neisseria spp. tested. The malate dehydrogenase patterns from the atypical neisserias and B. catarrhalis ATCC23246 were qualitatively similar; however, the patterns of isocitrate dehydrogenase activity were variable for these species. Micrococcus cryophilus was distinct in its esterase and dehydrogenase bands, strongly suggesting its taxon unrelatedness to the genus Branhammella or the atypical neisserias. Of the enzymes assayed, esterase proved to be the most reliable for taxonomic identifications.", "contents": "Enzyme electrophoretograms in the analysis of taxon relatedness of Micrococcus cryophilus, Branhamella catarrhalis and atypical Neisserias. Extracts were prepared from Micrococcus cryophilus, several strains of Branhamella catarrhalis and Neisseria spp. Esterases, NADP-dependent isocitrate dehydrogenase and malate dehydrogenase activities were assayed after electrophoresis of extracts of polyacrylamide gels. Except for Neisseria perflava and N. sicca which resolved activity bands for the acetate-esterase only, the remaining bacteria exhibited species-specific esterase patterns also for the propionate and butyrate substrates. The multiple esterase patterns from B. catarrhalis ATCC25238 were qualitatively and quantitatively different from those of B. catarrhalis ATCC23246. This finding and other evidence supports a taxonomic shift of the latter to a species level of that genus. The atypical neisserias N. caviae and N. ovis appeared to exhibit an intrageneric specificity in their esterase patterns with those from B. catarrhalis but not to the other Neisseria spp. tested. The malate dehydrogenase patterns from the atypical neisserias and B. catarrhalis ATCC23246 were qualitatively similar; however, the patterns of isocitrate dehydrogenase activity were variable for these species. Micrococcus cryophilus was distinct in its esterase and dehydrogenase bands, strongly suggesting its taxon unrelatedness to the genus Branhammella or the atypical neisserias. Of the enzymes assayed, esterase proved to be the most reliable for taxonomic identifications."}
{"id": "PMID:234508", "title": "Microbial water relations. Effects of solute concentration on the respiratory activity of sugar-tolerant and non-tolerant yeasts.", "content": "The respiratory activity of the sugar-tolerant (osmophilic) yeast, Saccharomyces rouxii, and the non-tolerant species, Sacchromyces cerevisiae, were compared after growth in a complex basal medium, the medium supplemented with polyethylene glycol (mol. wt 200) to give a water activity of 0-95, and the medium supplemented with glucose (24 and 36%, w/v). The properties compared were Qo2 (glucose), NADH oxidase activity of isolated mitochondrial fractions, and cytochrome content. When grown in the basal medium S. cerevisiae was somewhat more active than S. rouxii by all criteria. Growth in the media supplemented were high glucose concentrations produced catabolite repression of respiration in S. cerevisiae but not in S. rouxii. The implications of this difference for polyol biosynthesis and the water relations of the sugar-tolerant species are discussed.", "contents": "Microbial water relations. Effects of solute concentration on the respiratory activity of sugar-tolerant and non-tolerant yeasts. The respiratory activity of the sugar-tolerant (osmophilic) yeast, Saccharomyces rouxii, and the non-tolerant species, Sacchromyces cerevisiae, were compared after growth in a complex basal medium, the medium supplemented with polyethylene glycol (mol. wt 200) to give a water activity of 0-95, and the medium supplemented with glucose (24 and 36%, w/v). The properties compared were Qo2 (glucose), NADH oxidase activity of isolated mitochondrial fractions, and cytochrome content. When grown in the basal medium S. cerevisiae was somewhat more active than S. rouxii by all criteria. Growth in the media supplemented were high glucose concentrations produced catabolite repression of respiration in S. cerevisiae but not in S. rouxii. The implications of this difference for polyol biosynthesis and the water relations of the sugar-tolerant species are discussed."}
{"id": "PMID:234509", "title": "The basis of the alkalophilic property of a species of bacillus.", "content": "An alkalophilic bacterium belonging to the genus Bacillus was isolated from an indigo ball. The bacterium exhibited a maximum growth rate at pH 10-0 TO 10-5. The incorporation of 14C-labelled amino acids or [14C]uracil, uptake of 14C-labelled alpha-amino isobutyric acid into the bacterium and oxygen consumption of the bacterium with amino acids as substrates were all maximum at pH 9-0 to 10-5. The uptake of [U-14C]glucose into the organism and oxygen consumption with carbohydrates, on the other hand, showed little variation of rate in the pH 8 to 10 region. The oxygen consumption of intact bacteria or protoplasts in culture medium was maximum at pH 10. The membrane of the bacterium oxidized NADH maximally at pH 7-5, and ATPase bound to the membrane exhibited maximum activity at pH 7.L-Lactate, L-alanine and malate dehydrogenases in the soluble fraction exhibited maximum activities at pH 7-4 to 8-4. The alkalophilic property of the bacterium may be due to the behaviour of the membrane towards charged substances admitted into the organisms.", "contents": "The basis of the alkalophilic property of a species of bacillus. An alkalophilic bacterium belonging to the genus Bacillus was isolated from an indigo ball. The bacterium exhibited a maximum growth rate at pH 10-0 TO 10-5. The incorporation of 14C-labelled amino acids or [14C]uracil, uptake of 14C-labelled alpha-amino isobutyric acid into the bacterium and oxygen consumption of the bacterium with amino acids as substrates were all maximum at pH 9-0 to 10-5. The uptake of [U-14C]glucose into the organism and oxygen consumption with carbohydrates, on the other hand, showed little variation of rate in the pH 8 to 10 region. The oxygen consumption of intact bacteria or protoplasts in culture medium was maximum at pH 10. The membrane of the bacterium oxidized NADH maximally at pH 7-5, and ATPase bound to the membrane exhibited maximum activity at pH 7.L-Lactate, L-alanine and malate dehydrogenases in the soluble fraction exhibited maximum activities at pH 7-4 to 8-4. The alkalophilic property of the bacterium may be due to the behaviour of the membrane towards charged substances admitted into the organisms."}
{"id": "PMID:234510", "title": "Physiological studies on the pneumococcal Forssman antigen: a choline-containing lipoteichoic acid.", "content": "The cell concentration and possible biological activities of the pneumococcal Forssman (F) antigen (membrane lipoteichoic acid) were examined in a number of physiological situations. In test tube cultures of pneumococci the concentration of the Forssman antigen per bacterium showed no significant fluctuations within a typical culture cycle. Purified F antigen had no effect on the activation of pneumococci to competence for genetic transformation, DNA mediated genetic transformation or adsorption of the  pneumococcal phage Dp-1 to bacteria. Pneumococci grown in the presence of different amino alcohols (ethanolamine, N-monomethylethanolamine, or choline) exhibit differences with regard to both their ability to stimulate heterophile (haemolytic) antibody production in rabbits and in their ability to bind such antibodies. Choline-grown bacteria seem to cross-react with sheep red blood cells better than do the analogue-grown bacteria.", "contents": "Physiological studies on the pneumococcal Forssman antigen: a choline-containing lipoteichoic acid. The cell concentration and possible biological activities of the pneumococcal Forssman (F) antigen (membrane lipoteichoic acid) were examined in a number of physiological situations. In test tube cultures of pneumococci the concentration of the Forssman antigen per bacterium showed no significant fluctuations within a typical culture cycle. Purified F antigen had no effect on the activation of pneumococci to competence for genetic transformation, DNA mediated genetic transformation or adsorption of the  pneumococcal phage Dp-1 to bacteria. Pneumococci grown in the presence of different amino alcohols (ethanolamine, N-monomethylethanolamine, or choline) exhibit differences with regard to both their ability to stimulate heterophile (haemolytic) antibody production in rabbits and in their ability to bind such antibodies. Choline-grown bacteria seem to cross-react with sheep red blood cells better than do the analogue-grown bacteria."}
{"id": "PMID:234511", "title": "The structural gene for NADP L-glutamate dehydrogenase in Aspergillus nidulans.", "content": "A total of 41 mutants lacking NADP L-glutamate dehydrogenase (NADP-GDH) activity have been studied. All the mutations were located at the gdhA locus within 0-1% recombination of gdhAI. Two mutants, gdhAI and gdhA2, out of five examined, produced cross-reacting material which neutralized NADP-GDH anti-serum. The mutant gdhA9 has altered Km values for all five substrates: ammonium, alpha-ketoglutarate, l-glutamate, NADPH and NADP. The mutant gdhA20 had temperature-sensitive growth, abnormal ammonium-regulation characteristics and thermolabile NADP-GDH activity. These results show that gdhA is the structural gene for NADP-GDH.", "contents": "The structural gene for NADP L-glutamate dehydrogenase in Aspergillus nidulans. A total of 41 mutants lacking NADP L-glutamate dehydrogenase (NADP-GDH) activity have been studied. All the mutations were located at the gdhA locus within 0-1% recombination of gdhAI. Two mutants, gdhAI and gdhA2, out of five examined, produced cross-reacting material which neutralized NADP-GDH anti-serum. The mutant gdhA9 has altered Km values for all five substrates: ammonium, alpha-ketoglutarate, l-glutamate, NADPH and NADP. The mutant gdhA20 had temperature-sensitive growth, abnormal ammonium-regulation characteristics and thermolabile NADP-GDH activity. These results show that gdhA is the structural gene for NADP-GDH."}
{"id": "PMID:234512", "title": "Enniatin production by Fusarium sambucinum: primary, secondary, and unitary metabolism.", "content": "Fusarium sambucinum liquid surface cultures on semi-defined medium with glucose as carbon source passed through well-defined phases corresponding to trophophase, idiophase (enniatin production), and a degenerative phase. All the glucose was consumed by day 6, at which time the mycelial dry weight had reached only half its maximum. When glucose was replaced by lactose, there was no separation of trophophase and idiophase. Enniatin production, dry weight, and sugar and nitrogen consumption were in approximate balance throughout the growth period (25 days), after which slow degeneration began. The term 'unitary metabolism' is proposed for this type of unphased behaviour. Unitary metabolism may approximate more closely to that occurring under natural conditions than does the metabolic phase separation observed when rapidly utilized carbon sources are used in laboratory cultures.", "contents": "Enniatin production by Fusarium sambucinum: primary, secondary, and unitary metabolism. Fusarium sambucinum liquid surface cultures on semi-defined medium with glucose as carbon source passed through well-defined phases corresponding to trophophase, idiophase (enniatin production), and a degenerative phase. All the glucose was consumed by day 6, at which time the mycelial dry weight had reached only half its maximum. When glucose was replaced by lactose, there was no separation of trophophase and idiophase. Enniatin production, dry weight, and sugar and nitrogen consumption were in approximate balance throughout the growth period (25 days), after which slow degeneration began. The term 'unitary metabolism' is proposed for this type of unphased behaviour. Unitary metabolism may approximate more closely to that occurring under natural conditions than does the metabolic phase separation observed when rapidly utilized carbon sources are used in laboratory cultures."}
{"id": "PMID:234524", "title": "Use of 6-hydroxydopamine to create lesions in catecholamine neurons in rats.", "content": "The authors report experiments in rats with 6-hydroxydopamine (6-OHDA), a chemical agent used for creating lesions in catecholamine neurons. Stereotaxic injection of 6-OHDA into the compact zone of the substantia nigra induced degeneration of the nigrostriatal dopamine (DA) system, confirmed by histology and histochemistry of the substantia nigra and by dopamine determinations in the neostriatum. These observations closely mimic those found in Parkinson's disease. In the experimental model a rotatory behavior is induced by DA agonists; this response has been used to test drugs for potential therapeutic use and also in basic studies of the extrapyramidal system. This technique may be useful in developing other experimental models for neurosurgical problems involving catecholamine pathways.", "contents": "Use of 6-hydroxydopamine to create lesions in catecholamine neurons in rats. The authors report experiments in rats with 6-hydroxydopamine (6-OHDA), a chemical agent used for creating lesions in catecholamine neurons. Stereotaxic injection of 6-OHDA into the compact zone of the substantia nigra induced degeneration of the nigrostriatal dopamine (DA) system, confirmed by histology and histochemistry of the substantia nigra and by dopamine determinations in the neostriatum. These observations closely mimic those found in Parkinson's disease. In the experimental model a rotatory behavior is induced by DA agonists; this response has been used to test drugs for potential therapeutic use and also in basic studies of the extrapyramidal system. This technique may be useful in developing other experimental models for neurosurgical problems involving catecholamine pathways."}
{"id": "PMID:234525", "title": "Radionuclide detection of a pheochromocytoma.", "content": "An area of increased radioactivity was visualized superior to the right kidney during the flow phase of a routine radionuclide renal angiography using 99mTc-Sn-DTPA. This same area failed to concentrate the radiopharmaceutical during delayed static images. This sequence suggested a highly vascular mass above the right kidney. The mass proved to be an adrenal pheochromocytoma as was suggested by the radionuclide study.", "contents": "Radionuclide detection of a pheochromocytoma. An area of increased radioactivity was visualized superior to the right kidney during the flow phase of a routine radionuclide renal angiography using 99mTc-Sn-DTPA. This same area failed to concentrate the radiopharmaceutical during delayed static images. This sequence suggested a highly vascular mass above the right kidney. The mass proved to be an adrenal pheochromocytoma as was suggested by the radionuclide study."}
{"id": "PMID:234526", "title": "Cisternographic imaging patterns: effects of partial extra-arachnoid radiopharmaceutical injection and postinjection CSF leakage.", "content": "A cisternographic pattern of subarachnoid block with transient or no ventricular radiopharmaceutical reflux was observed in 52% of 105 patients with partial extra-arachnoid injections or postinjection leakage of CSF or both at the lumbar puncture site. In several patients, adequate repeat studies demonstrated considerably different CSF flow patterns. This block pattern was seen in only 11% of 217 patients with adequate intrathecal injections. Lumbar CSF leakage may alter the pattern seen on a cisternographic study and, if present, the study should be interpreted with caution.", "contents": "Cisternographic imaging patterns: effects of partial extra-arachnoid radiopharmaceutical injection and postinjection CSF leakage. A cisternographic pattern of subarachnoid block with transient or no ventricular radiopharmaceutical reflux was observed in 52% of 105 patients with partial extra-arachnoid injections or postinjection leakage of CSF or both at the lumbar puncture site. In several patients, adequate repeat studies demonstrated considerably different CSF flow patterns. This block pattern was seen in only 11% of 217 patients with adequate intrathecal injections. Lumbar CSF leakage may alter the pattern seen on a cisternographic study and, if present, the study should be interpreted with caution."}
{"id": "PMID:234527", "title": "Steroid effect on the brain scan in a patient with cerebral metastases.", "content": "A case of cerebral metastases is presented in which the initial brain scan did not demonstrate the lesion because steroid medication had been started 18 hr earlier. The lesion was seen after the patient had been off medication for several days. Therefore, brain scans should be performed prior to starting or following the removal of steroid medication for several days in order to avoid false-negative results secondary to steroid effects.", "contents": "Steroid effect on the brain scan in a patient with cerebral metastases. A case of cerebral metastases is presented in which the initial brain scan did not demonstrate the lesion because steroid medication had been started 18 hr earlier. The lesion was seen after the patient had been off medication for several days. Therefore, brain scans should be performed prior to starting or following the removal of steroid medication for several days in order to avoid false-negative results secondary to steroid effects."}
{"id": "PMID:234528", "title": "Alteration of porcine skin acid mucopolysaccharides in zinc deficiency.", "content": "Zinc deficiency is overtly manifested as a dermatitis in swine; therefore, the purpose of this investigation was to determine possible zinc-related alterations in the metabolism of the skin acid mucopolysaccharides (AMPs). Eighteen 4-week-old Yorkshire pigs were randomly allocated to one of three dietary treatments. Six animals were fed a semipurified, zinc-deficient, basal diet containing 20 ppm zinc. Six animals served as pair-fed controls and were fed the basal diet supplemented with 90 ppm zinc as zinc carbonate. The remaining six animals were fed the zinc-supplemented diet on and ad libitum schedule. All animals were killed after 36 days when overt deficiency symptoms were apparent in those animals fed 20 ppm zinc. Skin AMPs were isolated. Total hexosamine and galactosamine indicated no alteration in total AMPs. Fractionation of total AMPs into consitituent sulfated and nonsulfated components revealed a significant increase in hyaluronic acid. No statistical difference in sulfated AMPs was found in skin from deficient and pair-fed animals, which was in accord with an in vitro sulfur-35 uptake study.", "contents": "Alteration of porcine skin acid mucopolysaccharides in zinc deficiency. Zinc deficiency is overtly manifested as a dermatitis in swine; therefore, the purpose of this investigation was to determine possible zinc-related alterations in the metabolism of the skin acid mucopolysaccharides (AMPs). Eighteen 4-week-old Yorkshire pigs were randomly allocated to one of three dietary treatments. Six animals were fed a semipurified, zinc-deficient, basal diet containing 20 ppm zinc. Six animals served as pair-fed controls and were fed the basal diet supplemented with 90 ppm zinc as zinc carbonate. The remaining six animals were fed the zinc-supplemented diet on and ad libitum schedule. All animals were killed after 36 days when overt deficiency symptoms were apparent in those animals fed 20 ppm zinc. Skin AMPs were isolated. Total hexosamine and galactosamine indicated no alteration in total AMPs. Fractionation of total AMPs into consitituent sulfated and nonsulfated components revealed a significant increase in hyaluronic acid. No statistical difference in sulfated AMPs was found in skin from deficient and pair-fed animals, which was in accord with an in vitro sulfur-35 uptake study."}
{"id": "PMID:234530", "title": "Inflammatory disease of the colon: ulcerative colitis and Crohn's colitis.", "content": "Ulcerative colitis differs from Crohn's colitis in several ways. In ulcerative colitis the disease is limited to the mucosa and, occasionally, the submucosa; Crohn's colitis may involve all layers of the large intestine. Ulcerative colitis almost always begins in the rectum, is diffuse, and spreads proximally. Crohn's colitis may spare the rectum and has a patchy distribution. Perianal fistulas and ulcers are rare in ulcerative colitis but are common in Crohn's colitis. Granulomas and giant cells are not found in ulcerative colitis but are seen in the majority of patients with Crohn's colitis. Colonic and extraintestinal symptoms in the two illnesses may be indistinguishable but growth failure is far more severe in Crohn's colitis and may precede intestinal symptoms by months to years. Cancer of the colon is a risk in patients with either ulcerative or Crohn's colitis but is far more common in the former. It is important to distinguish between ulcerative colitis and Crohn's colitis because response to treatment and prognosis are different. Although neither condition can be cured by medical management, patients with ulcerative colitis may respond more frequently. Unfortunately, in the pediatric age range most cases of ulcerative and Crohn's colitis may be classified as moderate to severe. Fortunately for patients with ulcerative colitis, total colectomy with ileostomy will result in cure of illness. Patients with Crohn's colitis who require surgery may obtain remission of symptoms, but the disease is likely to recur in the small intestine.", "contents": "Inflammatory disease of the colon: ulcerative colitis and Crohn's colitis. Ulcerative colitis differs from Crohn's colitis in several ways. In ulcerative colitis the disease is limited to the mucosa and, occasionally, the submucosa; Crohn's colitis may involve all layers of the large intestine. Ulcerative colitis almost always begins in the rectum, is diffuse, and spreads proximally. Crohn's colitis may spare the rectum and has a patchy distribution. Perianal fistulas and ulcers are rare in ulcerative colitis but are common in Crohn's colitis. Granulomas and giant cells are not found in ulcerative colitis but are seen in the majority of patients with Crohn's colitis. Colonic and extraintestinal symptoms in the two illnesses may be indistinguishable but growth failure is far more severe in Crohn's colitis and may precede intestinal symptoms by months to years. Cancer of the colon is a risk in patients with either ulcerative or Crohn's colitis but is far more common in the former. It is important to distinguish between ulcerative colitis and Crohn's colitis because response to treatment and prognosis are different. Although neither condition can be cured by medical management, patients with ulcerative colitis may respond more frequently. Unfortunately, in the pediatric age range most cases of ulcerative and Crohn's colitis may be classified as moderate to severe. Fortunately for patients with ulcerative colitis, total colectomy with ileostomy will result in cure of illness. Patients with Crohn's colitis who require surgery may obtain remission of symptoms, but the disease is likely to recur in the small intestine."}
{"id": "PMID:234532", "title": "A common factor in the MMPI scales of married couples.", "content": "Using canonical analysis, a common factor in the MMPI scales of husbands and wives was found. The Sc, Pd, and Hs scales for both the husbands and the wives contributed heavily to the relationship. Other scales contributing to the correlation between the personality components of the pairs were F, Hy Pt, and Si for the husbands and Pa for the wives. The results were interpreted as indicating areas of homogeneity and heterogeneity in the personalities of married couples.", "contents": "A common factor in the MMPI scales of married couples. Using canonical analysis, a common factor in the MMPI scales of husbands and wives was found. The Sc, Pd, and Hs scales for both the husbands and the wives contributed heavily to the relationship. Other scales contributing to the correlation between the personality components of the pairs were F, Hy Pt, and Si for the husbands and Pa for the wives. The results were interpreted as indicating areas of homogeneity and heterogeneity in the personalities of married couples."}
{"id": "PMID:234534", "title": "Immunologic induction of malignant lymphoma: identification of donor and host tumors in the graft-versus-host model.", "content": "Primary lymphoid tumors were induced by inoculation of parental line spleen cells into H-2 incompatible F1 hybrid mice. The genotypes of lymphomas arising in 19 different parent yields F1 combinations were determined with cytotoxic antisera against H-2 specificities of donor and host. Additional chromosome marker studies established the reliability of tumor genotyping by the cytotoxicity test. According to H-2 typing, 12 primary lymphomas were of donor type, 66 of host type, and 14 of intermediate type. As a group, those parent yields F1 combinations in which donor-type lymphomas developed (group 1) showed a higher degree of histocompatibility between donor and host than those combinations in which donor-type lymphomas failed to appear (group 2). Allogeneic inhibition may have suppressed the development of donor-type tumors in the combinations of group 2. The development of malignant lymphomas of donor-type in the graft-versus-host reaction (GNHR) supports the concept of lymphomagenesis as a consequence of persistent stimulation by antigen.", "contents": "Immunologic induction of malignant lymphoma: identification of donor and host tumors in the graft-versus-host model. Primary lymphoid tumors were induced by inoculation of parental line spleen cells into H-2 incompatible F1 hybrid mice. The genotypes of lymphomas arising in 19 different parent yields F1 combinations were determined with cytotoxic antisera against H-2 specificities of donor and host. Additional chromosome marker studies established the reliability of tumor genotyping by the cytotoxicity test. According to H-2 typing, 12 primary lymphomas were of donor type, 66 of host type, and 14 of intermediate type. As a group, those parent yields F1 combinations in which donor-type lymphomas developed (group 1) showed a higher degree of histocompatibility between donor and host than those combinations in which donor-type lymphomas failed to appear (group 2). Allogeneic inhibition may have suppressed the development of donor-type tumors in the combinations of group 2. The development of malignant lymphomas of donor-type in the graft-versus-host reaction (GNHR) supports the concept of lymphomagenesis as a consequence of persistent stimulation by antigen."}
{"id": "PMID:234535", "title": "Interaction between aromatic diamidines and nucleic acids: possible implications for chemotherapy.", "content": "Interaction between aromatic diamidines (pentamidine, propamidine, and stilbamidine) and nucleic acids were studied to elucidate the mechanism underlying renal toxicity included by pentamidine in patients. Pentamidine, propamidine, and stilbamidine precipitated with RNA and DNA of all species and types. Furthermore, the diamidines interacted and precipitated with all nucleoside triphosphates and nucleoside diphosphates, but not with nucleoside monophosphates, nucleosides, or free bases. Nucleoside diphosphate is the minimum unit necessary for interaction with the diamidines. This interaction between diamidines and nucleotides or nucleic acids may be implicated in the etiology of renal damage and skin reactions associated with these drugs.", "contents": "Interaction between aromatic diamidines and nucleic acids: possible implications for chemotherapy. Interaction between aromatic diamidines (pentamidine, propamidine, and stilbamidine) and nucleic acids were studied to elucidate the mechanism underlying renal toxicity included by pentamidine in patients. Pentamidine, propamidine, and stilbamidine precipitated with RNA and DNA of all species and types. Furthermore, the diamidines interacted and precipitated with all nucleoside triphosphates and nucleoside diphosphates, but not with nucleoside monophosphates, nucleosides, or free bases. Nucleoside diphosphate is the minimum unit necessary for interaction with the diamidines. This interaction between diamidines and nucleotides or nucleic acids may be implicated in the etiology of renal damage and skin reactions associated with these drugs."}
{"id": "PMID:234536", "title": "Stability of nitrosamines in samples of lake water, soil, and sewage.", "content": "N-nitrosodimethylamine, N-nitrosodiethylamine, and N-nitrosodi-n-propylamine were resistant to degradation in soil, sewage, and lake water. No degradation of these nitrosamines was observed in lake water during a 3.5-month period. A lag of nearly 30 days occurred before their slow disappearance from soil; they disappeared slowly from sewage, but a minimum of 50% remained after 14 days. The results with sewage and soil suggesta a microbial involvement in the slow decomposition of these nitrosamines.", "contents": "Stability of nitrosamines in samples of lake water, soil, and sewage. N-nitrosodimethylamine, N-nitrosodiethylamine, and N-nitrosodi-n-propylamine were resistant to degradation in soil, sewage, and lake water. No degradation of these nitrosamines was observed in lake water during a 3.5-month period. A lag of nearly 30 days occurred before their slow disappearance from soil; they disappeared slowly from sewage, but a minimum of 50% remained after 14 days. The results with sewage and soil suggesta a microbial involvement in the slow decomposition of these nitrosamines."}
{"id": "PMID:234537", "title": "Suppression and regression of a transplanted tumor in the guinea pig colon mediated by Mycobacterium bovis, strain BCG.", "content": "The growth in the colon wall of a diethylnitrosamine-induced hepatocarcinoma was suppressed by BCG. Injection of BCG into established colon-wall tumors caused tumor regression. Successful therapy required a limited tumor burden. Guinea pigs in which growth of the neoplasm was suppressed at the site of BCG infection developed systemic tumor transplantation immunity.", "contents": "Suppression and regression of a transplanted tumor in the guinea pig colon mediated by Mycobacterium bovis, strain BCG. The growth in the colon wall of a diethylnitrosamine-induced hepatocarcinoma was suppressed by BCG. Injection of BCG into established colon-wall tumors caused tumor regression. Successful therapy required a limited tumor burden. Guinea pigs in which growth of the neoplasm was suppressed at the site of BCG infection developed systemic tumor transplantation immunity."}
{"id": "PMID:234538", "title": "Interaction of Sindbis virus with liposomal model membranes.", "content": "Radiolabeled Sindbis virus was found to bind to protein-free lipid model membranes (liposomes) derived from extracts of sheep erythrocytes. The virus interaction was dependent on initial pH, and the range of pH dependence (pH 6.0 to 6.8) was the same as the observed with virus-dependent hemagglutination. After the initial interaction, pH changes no longer influenced the virus binding to liposomes. Virus bound to liposomes prepared from a mixture of erythrocyte phospholipids, but the binding was greatly diminished when either cholesterol or phosphatidylethanolamine was omitted from the liposomal lipid mixture. It was concluded that phospholipids and cholesterol, in a bilayer configuration, may be sufficient for specific virus binding in the absence of membrane protein.", "contents": "Interaction of Sindbis virus with liposomal model membranes. Radiolabeled Sindbis virus was found to bind to protein-free lipid model membranes (liposomes) derived from extracts of sheep erythrocytes. The virus interaction was dependent on initial pH, and the range of pH dependence (pH 6.0 to 6.8) was the same as the observed with virus-dependent hemagglutination. After the initial interaction, pH changes no longer influenced the virus binding to liposomes. Virus bound to liposomes prepared from a mixture of erythrocyte phospholipids, but the binding was greatly diminished when either cholesterol or phosphatidylethanolamine was omitted from the liposomal lipid mixture. It was concluded that phospholipids and cholesterol, in a bilayer configuration, may be sufficient for specific virus binding in the absence of membrane protein."}
{"id": "PMID:234539", "title": "pH stability studies with avian infectious bronchitis virus (coronavirus) strains.", "content": "A comparison of 17 infectious bronchitis virus strains, using the same test procedure and assay system, demonstrated that stability at an acid pH is a variable characteristic of the avian coronaviruses.", "contents": "pH stability studies with avian infectious bronchitis virus (coronavirus) strains. A comparison of 17 infectious bronchitis virus strains, using the same test procedure and assay system, demonstrated that stability at an acid pH is a variable characteristic of the avian coronaviruses."}
{"id": "PMID:234540", "title": "Electron microscopy of simian virus 40 DNA configuration under denaturation conditions.", "content": "After isolation, the DNA of simian virus 40 appeared as a negative supertwist (form I) or as an open circle with at least one single-strand scission (form II). Under the denaturation conditions usually applied, such as heating in the presence of formaldehyde or application of alkali, form I molecules could appear as \"relaxed\" circles without single-strand scissions (form I') containing denatured sites not visible under the electron microscope. Form II molecules, under these denaturation conditions, showed partial or complete strand separations allowing the construction of denaturation maps. By using a modified denaturation procedure, i.e., heating of isolated SV40 DNA in the presence of dimethyl sulfoxide and formaldehyde followed by keeping the DNA in this denaturation solution at room temperature for periods up to 3 weeks, partially denatured relaxed circles without single-strand scissions were produced (form I'D) in addition to completely denatured form II molecules. The absence of single-strand scissions in form I'D molecules was demonstrated by a second heat treatment, which did not change the configuration of this molecular form. Form I'D molecules, in contrast to form I', contained denatured sites clearly discerible under the electron microscope. This combined application of two subsequent denaturation steps (denaturation by heating followed by denaturation at room temperature and neutral pH) showed that the molecular configuration I'D originated in two steps. The heating procedure produced molecules not distinquishable by electron microscopy from form I. In contrast to form I, these molecules were assumed to possess \"preformed\" denaturation sites (form I). Further treatment of form I molecules with denaturation solution at room temperature finally transformed them into convalently closed, relaxed, partially denatured circles exhibiting strand separations easily measurable on electron micrographs (form I'D). Denaturation maps of form I'D molecules were constructed by computer and compared with denaturation maps derived from partially denatured form II molecules. From these denaturation maps it can be concluded that the melting of base pairs occurring during the transition of simian virus 40 DNA form I into form I'D also preferentially happened at sites rich in the bases adenosine and thymine.", "contents": "Electron microscopy of simian virus 40 DNA configuration under denaturation conditions. After isolation, the DNA of simian virus 40 appeared as a negative supertwist (form I) or as an open circle with at least one single-strand scission (form II). Under the denaturation conditions usually applied, such as heating in the presence of formaldehyde or application of alkali, form I molecules could appear as \"relaxed\" circles without single-strand scissions (form I') containing denatured sites not visible under the electron microscope. Form II molecules, under these denaturation conditions, showed partial or complete strand separations allowing the construction of denaturation maps. By using a modified denaturation procedure, i.e., heating of isolated SV40 DNA in the presence of dimethyl sulfoxide and formaldehyde followed by keeping the DNA in this denaturation solution at room temperature for periods up to 3 weeks, partially denatured relaxed circles without single-strand scissions were produced (form I'D) in addition to completely denatured form II molecules. The absence of single-strand scissions in form I'D molecules was demonstrated by a second heat treatment, which did not change the configuration of this molecular form. Form I'D molecules, in contrast to form I', contained denatured sites clearly discerible under the electron microscope. This combined application of two subsequent denaturation steps (denaturation by heating followed by denaturation at room temperature and neutral pH) showed that the molecular configuration I'D originated in two steps. The heating procedure produced molecules not distinquishable by electron microscopy from form I. In contrast to form I, these molecules were assumed to possess \"preformed\" denaturation sites (form I). Further treatment of form I molecules with denaturation solution at room temperature finally transformed them into convalently closed, relaxed, partially denatured circles exhibiting strand separations easily measurable on electron micrographs (form I'D). Denaturation maps of form I'D molecules were constructed by computer and compared with denaturation maps derived from partially denatured form II molecules. From these denaturation maps it can be concluded that the melting of base pairs occurring during the transition of simian virus 40 DNA form I into form I'D also preferentially happened at sites rich in the bases adenosine and thymine."}
{"id": "PMID:234546", "title": "Left and right ventricular volumes in A-V block, and their changes induced by the infusion of isoproterenol.", "content": "In mongrel dogs (14.5 to 26.3 Kg) during complete heart block and right ventricular pacing, the cardiovascular dynamics were observed with the effect of isoproterenol infusion (8 mug/min intravenously). During complete heart block, cardiac output 2.01 plus or minus 0.17 L/min, heart rate 57.6 plus or minus 3. 5 beats/min, and stroke volume 35.5 plus or minus 2%. Left ventricular (LV) residual fraction was 54 plus or minus 2%. LV end-diastolic volume (EDV) IN WHich almost complete filling is performed due to the long filling period was 4.01 plus orminus 0.35 ml/Kg by thermodilution method. Right ventricular (RV) residual fraction and EDV were 39 plus or minus 3% and 3.01 ml/Kg, which were significantly smaller than the left. Infusion of isoproterenol increased cardiac output (2.67 plus or minus 0.21 L/min), heart rate (66.9 plus or minus 3.5 beats/min), and stroke volume (40.4 plus or minus 3.1 ml), but both ventricular residual fractions and EDV's didnot change significantly, although mean blood pressure decreased remarkably. During right ventricular pacing the effects of isoproterenol were essentially the same as in complete heart block except no change of heart rate and relatively improved cardiac functions. The plots of derived force-velocity relationship expressed in normalized mean circumferential shortening rate (MCSR) and peak ventricular force (F) showed that isoproterenol increased the velocity of shortening of muscle contraction significantly without significant change of F, while increase of heart rate didnot. It is concluded that isoproterenol affects the myocardium mainly throughits direct action and the improvement of contractile state via positive chronotropic effect (Bowditch's effect) is relatively small.", "contents": "Left and right ventricular volumes in A-V block, and their changes induced by the infusion of isoproterenol. In mongrel dogs (14.5 to 26.3 Kg) during complete heart block and right ventricular pacing, the cardiovascular dynamics were observed with the effect of isoproterenol infusion (8 mug/min intravenously). During complete heart block, cardiac output 2.01 plus or minus 0.17 L/min, heart rate 57.6 plus or minus 3. 5 beats/min, and stroke volume 35.5 plus or minus 2%. Left ventricular (LV) residual fraction was 54 plus or minus 2%. LV end-diastolic volume (EDV) IN WHich almost complete filling is performed due to the long filling period was 4.01 plus orminus 0.35 ml/Kg by thermodilution method. Right ventricular (RV) residual fraction and EDV were 39 plus or minus 3% and 3.01 ml/Kg, which were significantly smaller than the left. Infusion of isoproterenol increased cardiac output (2.67 plus or minus 0.21 L/min), heart rate (66.9 plus or minus 3.5 beats/min), and stroke volume (40.4 plus or minus 3.1 ml), but both ventricular residual fractions and EDV's didnot change significantly, although mean blood pressure decreased remarkably. During right ventricular pacing the effects of isoproterenol were essentially the same as in complete heart block except no change of heart rate and relatively improved cardiac functions. The plots of derived force-velocity relationship expressed in normalized mean circumferential shortening rate (MCSR) and peak ventricular force (F) showed that isoproterenol increased the velocity of shortening of muscle contraction significantly without significant change of F, while increase of heart rate didnot. It is concluded that isoproterenol affects the myocardium mainly throughits direct action and the improvement of contractile state via positive chronotropic effect (Bowditch's effect) is relatively small."}
{"id": "PMID:234547", "title": "Hyperreactive arterial endothelial cells in atherogenesis and cyclic AMP phosphodiesterase inhibitor in prevention and treatment of atherosclerotic disorders.", "content": "The hyperreactive arterial endothelial cells have been introduced in this paper. They are characterized by their ability to transport particles too large for the small holes of the internal elastic lamina locating underneath the endothelial cells, such as carbon particles with the similar size of LDL, floating beta-lipoprotein, Lp(a) and especially of VLDL, into the subendothelial space from the blood stream by their abnormally strong contracting and phagocytosis-like activity. Large particles such as carbon particles with a size of 200 to 700 angstrom are too large to penetrate further through holes of the internal elastic lamina from the subendothelial space to muscular layers of the arterial wall, resulting in stagnating for a long time in the subendothelial space, thus showing the atherogenic property of the hyperreactive arterial endothelial cells. Such endothelial cells appear spotty and streaky in the localized endothelial lining of predominantly susceptible parts to atherosclerosis in susceptible animal species such as rabbit, chicken, and rhesus monkey especially densely in their atheromatous lesions, but do not generally appear in non-susceptible animals to atherosclerosis like rate and dog. They are extremely few in infant rabbit, but increase by age.They appear in hypertensive rat, showing a characteristic distribution even in small groups of arteriessuch as the circle of Willis. Cyclic AMP, and especially dibutyryl cyclic AMP, exhibited an inhibitory effect on the hyperreactivity of those cells. Cyclic AMP phosphodiesterase inhibitors, EG467 and eg626, exhibited a powerful inhibitory effect on the contracting and phagocytosis-like activity of those cells, as in the case of pyridinolcarbamate, which enhances enzymes to produce ATP and inhibits slightly cyclic AMP phosphodiesterase, although its inhibitory effect on cyclic AMP phosphodiesterase is weaker than that of EF467 and EG626. The usefulness of the inhibitors on cyclic AMP phospodiesterase of arterial endothelial cells and platelets and on that of brain, such as EG467 AND EG626, has been suggested in the treatment of atherosclerotic disorders, especially of cerebral atherosclerosis. Some of the hitherto desperate mental disability of the aged seem to be a promising target for treatment with cyclic AMP phosphodiesterase inhibitors.", "contents": "Hyperreactive arterial endothelial cells in atherogenesis and cyclic AMP phosphodiesterase inhibitor in prevention and treatment of atherosclerotic disorders. The hyperreactive arterial endothelial cells have been introduced in this paper. They are characterized by their ability to transport particles too large for the small holes of the internal elastic lamina locating underneath the endothelial cells, such as carbon particles with the similar size of LDL, floating beta-lipoprotein, Lp(a) and especially of VLDL, into the subendothelial space from the blood stream by their abnormally strong contracting and phagocytosis-like activity. Large particles such as carbon particles with a size of 200 to 700 angstrom are too large to penetrate further through holes of the internal elastic lamina from the subendothelial space to muscular layers of the arterial wall, resulting in stagnating for a long time in the subendothelial space, thus showing the atherogenic property of the hyperreactive arterial endothelial cells. Such endothelial cells appear spotty and streaky in the localized endothelial lining of predominantly susceptible parts to atherosclerosis in susceptible animal species such as rabbit, chicken, and rhesus monkey especially densely in their atheromatous lesions, but do not generally appear in non-susceptible animals to atherosclerosis like rate and dog. They are extremely few in infant rabbit, but increase by age.They appear in hypertensive rat, showing a characteristic distribution even in small groups of arteriessuch as the circle of Willis. Cyclic AMP, and especially dibutyryl cyclic AMP, exhibited an inhibitory effect on the hyperreactivity of those cells. Cyclic AMP phosphodiesterase inhibitors, EG467 and eg626, exhibited a powerful inhibitory effect on the contracting and phagocytosis-like activity of those cells, as in the case of pyridinolcarbamate, which enhances enzymes to produce ATP and inhibits slightly cyclic AMP phosphodiesterase, although its inhibitory effect on cyclic AMP phosphodiesterase is weaker than that of EF467 and EG626. The usefulness of the inhibitors on cyclic AMP phospodiesterase of arterial endothelial cells and platelets and on that of brain, such as EG467 AND EG626, has been suggested in the treatment of atherosclerotic disorders, especially of cerebral atherosclerosis. Some of the hitherto desperate mental disability of the aged seem to be a promising target for treatment with cyclic AMP phosphodiesterase inhibitors."}
{"id": "PMID:234550", "title": "[Equation of the helix for separating plants in a spiral-radial cultivator].", "content": "Highly effective and compact cultivators must pullapart plants during vegetation in order to save light energy and area under crops. Cultivators ensuring a helical method for pulling plants apart are already available. The present paper suggests the criteria of the efficiency of using the area under crops of the cultivator and deformation of the leaf crown of plants (sigma- and delta-spectra). With respect to these values the main task of calculating the helix has been formulated. Having Chinese cabbage as an illustration, an equation of the helix has been derived. With the aid of the equation an optimal helix can be marked along the circle in polar coordinates.", "contents": "[Equation of the helix for separating plants in a spiral-radial cultivator]. Highly effective and compact cultivators must pullapart plants during vegetation in order to save light energy and area under crops. Cultivators ensuring a helical method for pulling plants apart are already available. The present paper suggests the criteria of the efficiency of using the area under crops of the cultivator and deformation of the leaf crown of plants (sigma- and delta-spectra). With respect to these values the main task of calculating the helix has been formulated. Having Chinese cabbage as an illustration, an equation of the helix has been derived. With the aid of the equation an optimal helix can be marked along the circle in polar coordinates."}
{"id": "PMID:234554", "title": "Mitochondrial changes in dog myocardium induced by lowered pH in vitro.", "content": "The effects of increased acidity and of lactate at acid pH values on the ultrastruct of normal dog myocardium were investigated using a simple in vitro system. Thin tissue slices incubated in isotonic, phosphate-buffered sodium chloride at pH 6.5, 6.8, or 7.0 developed within 10 minutes electron-dense mitochondrial inclusions resembling those seen in dog heart muscle after 40 or more minutes of ischemia. Mitochondria of tissue incubated in a comparable medium incorporating 3000 mu g. of lactate per ml. showed similar electron-dense inclusions, together with marked swelling. These results indicate that lowered tissue pH alone is not responsible for the mitochondrial changes typical of ischemic heart muscle. Since an earlier study has shown that marked mitochondrial swelling without dense granule formation can be produced by incubation of tissue in lactate at physiologic pH, it seems likely that the swelling of mitochondria in ischemic myocardium is due to the accumulation of lactate anions, whereas the development of the mitochondrial inclusions is associated with decreased pH.", "contents": "Mitochondrial changes in dog myocardium induced by lowered pH in vitro. The effects of increased acidity and of lactate at acid pH values on the ultrastruct of normal dog myocardium were investigated using a simple in vitro system. Thin tissue slices incubated in isotonic, phosphate-buffered sodium chloride at pH 6.5, 6.8, or 7.0 developed within 10 minutes electron-dense mitochondrial inclusions resembling those seen in dog heart muscle after 40 or more minutes of ischemia. Mitochondria of tissue incubated in a comparable medium incorporating 3000 mu g. of lactate per ml. showed similar electron-dense inclusions, together with marked swelling. These results indicate that lowered tissue pH alone is not responsible for the mitochondrial changes typical of ischemic heart muscle. Since an earlier study has shown that marked mitochondrial swelling without dense granule formation can be produced by incubation of tissue in lactate at physiologic pH, it seems likely that the swelling of mitochondria in ischemic myocardium is due to the accumulation of lactate anions, whereas the development of the mitochondrial inclusions is associated with decreased pH."}
{"id": "PMID:234555", "title": "Land\u00e9-Edwards membrane oxygenator without pump as total lung prosthesis.", "content": "Fourteen anesthetized dogs remained in apnea for 1 to 4 hours on total extracorporeal breathing through a Land\u00e9-Edwards membrane oxygenator (LEMO). The LEMO was directly perfused by the right heart in total pulmonary bypass, without a pump or reservoir, as an external artificial lung. A 2 sq. M. LEMO proved adequate for a dog weighing 10 kiolgrams. Pulmonary arterial pressure increased 60 per cent of the base-line value at the start of bypass because of transitory LEMO resistance, three times the normal pulmonary resistance; the pressure then returned to the initial value. Systemic arterial pressure dropped to 61 per cent on bypass. The heart did not fail. Cardiac output, central venous pressure, and the electrocardiogram remained unchanged. PO2 at the LEMO outlet was more than 200 mm. Hg. Oxygen transfer was less than 20 ml. per minute per square meter because of hemodilution and hypothermia. Dogs survived if bypass was arrested after 1 hour; if not, they died after an average of 3 hours, 20 minutes on bypass.", "contents": "Land\u00e9-Edwards membrane oxygenator without pump as total lung prosthesis. Fourteen anesthetized dogs remained in apnea for 1 to 4 hours on total extracorporeal breathing through a Land\u00e9-Edwards membrane oxygenator (LEMO). The LEMO was directly perfused by the right heart in total pulmonary bypass, without a pump or reservoir, as an external artificial lung. A 2 sq. M. LEMO proved adequate for a dog weighing 10 kiolgrams. Pulmonary arterial pressure increased 60 per cent of the base-line value at the start of bypass because of transitory LEMO resistance, three times the normal pulmonary resistance; the pressure then returned to the initial value. Systemic arterial pressure dropped to 61 per cent on bypass. The heart did not fail. Cardiac output, central venous pressure, and the electrocardiogram remained unchanged. PO2 at the LEMO outlet was more than 200 mm. Hg. Oxygen transfer was less than 20 ml. per minute per square meter because of hemodilution and hypothermia. Dogs survived if bypass was arrested after 1 hour; if not, they died after an average of 3 hours, 20 minutes on bypass."}
{"id": "PMID:234556", "title": "Experimental coronary artery fistula.", "content": "Despite numerous clinical reports of coronary artery fistulas, there have been no laboratory models. A circumflex coronary-pulmonary artery fistula was constructed with a vein graft in 11 adult foxhounds. A temporary intravascular shunt obviated the need for cardiopulmonary bypass. Measurements of aortic flow, arterial pressure, left ventricular pressure and its derivative, heart rate, and flow in the proximal coronary, distal coronary, and fistula were made with the fistula open and closed in 9 animals. Mean fistula  flow was 89 c.c. per minute, representing a 1.1:1 left-to-right shunt. Mean proximal coronary flow increased 211 per cent, and there was a relative steal of 26 per cent of distal coronary flow with the fistula functioning. Phasic flow patterns showed continuous systolic and diastolic flow in the proximal coronary artery and fistula. Despite the striking changes in coronary flow patterns, there was no significant effect on measured left ventricular function. Futher uses for this model and variations of it aresuggested.", "contents": "Experimental coronary artery fistula. Despite numerous clinical reports of coronary artery fistulas, there have been no laboratory models. A circumflex coronary-pulmonary artery fistula was constructed with a vein graft in 11 adult foxhounds. A temporary intravascular shunt obviated the need for cardiopulmonary bypass. Measurements of aortic flow, arterial pressure, left ventricular pressure and its derivative, heart rate, and flow in the proximal coronary, distal coronary, and fistula were made with the fistula open and closed in 9 animals. Mean fistula  flow was 89 c.c. per minute, representing a 1.1:1 left-to-right shunt. Mean proximal coronary flow increased 211 per cent, and there was a relative steal of 26 per cent of distal coronary flow with the fistula functioning. Phasic flow patterns showed continuous systolic and diastolic flow in the proximal coronary artery and fistula. Despite the striking changes in coronary flow patterns, there was no significant effect on measured left ventricular function. Futher uses for this model and variations of it aresuggested."}
{"id": "PMID:234557", "title": "Dental health status of third grade children and their families within the context of a community's dental health care system.", "content": "Utilizing structure, process, and outcomes as conceptual dimensions of appraisal of quality, data were analyzed to present an evaluation of the quality of a community's dental health care system as reflected in a population subgroups' dental health status. Data were collected from 838 Caucasian third-graders and their parents through interviews, mail questionnaires, and dental screening examinations. Indicators of structure were: status of community water fluoridation in the study community, dentist to population ratio, and dental care resources in the public sector available to eligible residents. Process indicators of quality were: 1) screening, case finding, examinations, and quality of restorations as measures of provider behaviors, and 2) complaints, compliance, conditioned behaviors, level of dental health knowledge, and utilization of dental services as measures of client behaviors. Outcomes, subjected to analysis included indices indicative of dental disease experience. Variables operationally defined as indicators of the subgroup's dental health status were subjected to a descriptive analysis and were then crosstabulated with the socioeconomic status of the child's family to identify socioeconomic differences in the process of obtaining care and in dental health outcomes. Findings indicate which elements in a community's prevailing dental health care system function well and which would need alteration to maximize dental health for the subgroup.", "contents": "Dental health status of third grade children and their families within the context of a community's dental health care system. Utilizing structure, process, and outcomes as conceptual dimensions of appraisal of quality, data were analyzed to present an evaluation of the quality of a community's dental health care system as reflected in a population subgroups' dental health status. Data were collected from 838 Caucasian third-graders and their parents through interviews, mail questionnaires, and dental screening examinations. Indicators of structure were: status of community water fluoridation in the study community, dentist to population ratio, and dental care resources in the public sector available to eligible residents. Process indicators of quality were: 1) screening, case finding, examinations, and quality of restorations as measures of provider behaviors, and 2) complaints, compliance, conditioned behaviors, level of dental health knowledge, and utilization of dental services as measures of client behaviors. Outcomes, subjected to analysis included indices indicative of dental disease experience. Variables operationally defined as indicators of the subgroup's dental health status were subjected to a descriptive analysis and were then crosstabulated with the socioeconomic status of the child's family to identify socioeconomic differences in the process of obtaining care and in dental health outcomes. Findings indicate which elements in a community's prevailing dental health care system function well and which would need alteration to maximize dental health for the subgroup."}
{"id": "PMID:234552", "title": "[Use of electric stimulation to prevent the development of muscle changes during hypokinesia].", "content": "An attempt was made to use electric stimulation of antigravity muscles of hind limbs of rats exposed to a 15 and 30 day hypokinesia as a method for preventing structural and metabolic disorders that develop in the muscular tissue during a diminished motor activity. The electric stimulation was carried out using the Bion device with a frequency-amplitude modulation. The impulses of an amplitude of 0.7-1 msec and a frequency of 100 to 130 Hz were modulated with a frequency of 0.5 Hz. During the first experimental days the electric stimulation was 5 to 7 min and by the end of the first week it reached 30 min. Throughout the first week the voltage grew from 6-7 to 20 V. Electric stimulation was applied 5 times a week. The favourable effect of the electric stimulation was demonstrated in 4 out of 12 animals during every experimental run. It is suggested that a higher percentage of the protective effect of the method can be achieved with the stimulation ensuring a more intensive influence on the deeply located muscles.", "contents": "[Use of electric stimulation to prevent the development of muscle changes during hypokinesia]. An attempt was made to use electric stimulation of antigravity muscles of hind limbs of rats exposed to a 15 and 30 day hypokinesia as a method for preventing structural and metabolic disorders that develop in the muscular tissue during a diminished motor activity. The electric stimulation was carried out using the Bion device with a frequency-amplitude modulation. The impulses of an amplitude of 0.7-1 msec and a frequency of 100 to 130 Hz were modulated with a frequency of 0.5 Hz. During the first experimental days the electric stimulation was 5 to 7 min and by the end of the first week it reached 30 min. Throughout the first week the voltage grew from 6-7 to 20 V. Electric stimulation was applied 5 times a week. The favourable effect of the electric stimulation was demonstrated in 4 out of 12 animals during every experimental run. It is suggested that a higher percentage of the protective effect of the method can be achieved with the stimulation ensuring a more intensive influence on the deeply located muscles."}
{"id": "PMID:234566", "title": "Nondependence of cell pH on sodium transport in rat diaphragm muscle.", "content": "Both sodium and hydrogen ions are in lower concentration in muscle cell water than would be predicted from thermodynamic considerations alone, indicating active transport of these two ions out of muscle cells, To determine whether their transport is coupled, intact rat diaphragms were incubated at an external pH of 7.40, and sodium efflux was altered by exposure to ouabain. Despite a sixfold increase in intracellular sodium concentration, cell pH measured simultaneously by the distribution of both a weak acid (pH DMO) and a weak base (pH nicotine) was unaffected. Similarly, when sodium influx was decreased by incubating intact diaphragms in low sodium isoosmolar buffer, pH DMO and pH nicotine were unaltered. In addition, a pH-sensitive reaction, the evolution of 14CO2 from 1, 4-14C citrate by rat hemidiaphragm, was not changed by exposure to ouabain or low sodium media. These experiments demonstrate that in diaphragm muscle sodium and hydrogen ion transport appear not to be coupled, since alterations in sodium transport are unaccompanied by a change in cell pH. Although changes in membrane potential may explain part of the results, the data are most consistent with the hypothesis that active hydrogen ion transport in skeletal muscle in directly coupled to metabolic energy-producing reactions.", "contents": "Nondependence of cell pH on sodium transport in rat diaphragm muscle. Both sodium and hydrogen ions are in lower concentration in muscle cell water than would be predicted from thermodynamic considerations alone, indicating active transport of these two ions out of muscle cells, To determine whether their transport is coupled, intact rat diaphragms were incubated at an external pH of 7.40, and sodium efflux was altered by exposure to ouabain. Despite a sixfold increase in intracellular sodium concentration, cell pH measured simultaneously by the distribution of both a weak acid (pH DMO) and a weak base (pH nicotine) was unaffected. Similarly, when sodium influx was decreased by incubating intact diaphragms in low sodium isoosmolar buffer, pH DMO and pH nicotine were unaltered. In addition, a pH-sensitive reaction, the evolution of 14CO2 from 1, 4-14C citrate by rat hemidiaphragm, was not changed by exposure to ouabain or low sodium media. These experiments demonstrate that in diaphragm muscle sodium and hydrogen ion transport appear not to be coupled, since alterations in sodium transport are unaccompanied by a change in cell pH. Although changes in membrane potential may explain part of the results, the data are most consistent with the hypothesis that active hydrogen ion transport in skeletal muscle in directly coupled to metabolic energy-producing reactions."}
{"id": "PMID:234602", "title": "A pharmacologic comparison of histamine receptors in isolated extracranial and intracranial arteries in vitro.", "content": "Isolated segments of cat extracranial and intracranial arteries were tested simultaneously for circular motor activity in an aerated Krebs-Ringer organ bath at constant temperature and pH. Histamine produced a strong contraction (about 850 dyn) in the extracranial arteries but a considerably weaker contraction, with a high half maximum response, in the intracranial arteries. The mode of inhibition of the latter response by antihistaminic compounds (chlorpheniramine and mepyramine) showed the response to be nonspecific; the contraction in the extracranial arteries was inhibited in a competitive manner, demonstrating the presence of histamine H1 receptors. The dilatory response was studied after the vessels had been given a tonic contraction with serotonin. Histamine produced similar dilatory effects (about 200 dyn) in both types of arteries and competitive inhibitions were obtained with burimamide, showing that the dilation was mediated through histamine H2 receptors. Dissociation constants were calculated for the receptor-antagonist complex.", "contents": "A pharmacologic comparison of histamine receptors in isolated extracranial and intracranial arteries in vitro. Isolated segments of cat extracranial and intracranial arteries were tested simultaneously for circular motor activity in an aerated Krebs-Ringer organ bath at constant temperature and pH. Histamine produced a strong contraction (about 850 dyn) in the extracranial arteries but a considerably weaker contraction, with a high half maximum response, in the intracranial arteries. The mode of inhibition of the latter response by antihistaminic compounds (chlorpheniramine and mepyramine) showed the response to be nonspecific; the contraction in the extracranial arteries was inhibited in a competitive manner, demonstrating the presence of histamine H1 receptors. The dilatory response was studied after the vessels had been given a tonic contraction with serotonin. Histamine produced similar dilatory effects (about 200 dyn) in both types of arteries and competitive inhibitions were obtained with burimamide, showing that the dilation was mediated through histamine H2 receptors. Dissociation constants were calculated for the receptor-antagonist complex."}
{"id": "PMID:234604", "title": "[Physiological basis of homeostasis of the extracellular fluid volume].", "content": "Renal, glomerular and tubular, factors responsible for the volume control of extracellular liquid were examined. The part played by angiotensin II in mediating the compensation of this liquid losses was studied in patients with spontaneous polyuria due to diencephalo-posthypophyseal diabetes insipidus or psychogenic polydipsia and healthy subjects with induced hypotonic polyuria. It was noted that: 1) acute expansion elicited a natriuretic response and increased distal sodium load, due to an increase in filtrate and relative inhibition of proximal reabsorption, or proximal inhibition if the filtrate was unchanged. The efficiency of distal sodium transport was often unchanged. 2) Return to sodium balance parity during prolonged expansion of volume, was accomplished by varying renal means, in accordance with the experimental model employed. Distal reabsorption was essentially depressed during prolonged saline load (secondary hypoaldosteronism). When protracted mineralcorticoid treatment was used, however, distal reabsorption was high, even in the escape stage, and its saturation required marked augmentation of the sodium load reaching the distal tubules. 3) Depletion of volume caused by protracted natriuretic treatment in spontaneous polyuria reduced both diuresis and sodium excretion. This resistance to the natriuretic effect of the drug followed intrarenal compensation that reduced the distal sodium load and encouraged reabsorption in some distal sites (secondary hyperaldosteronism). 4) Infusion of angiotensin II in sub- or pauci-pressor doses causes an isosmotic sodium saving, since it reduced the glomerular filtrate and increases the fraction of filtrate reabsorbed by the proximal tubules; the tubular effect is likely secondary to increased vascular, especially postglomerular resistance. In the healthy subject, angiotensin II leads to antidiuresis referable, on account of its intensity and longer time cycle, to ADH release angiotensin-dependent.", "contents": "[Physiological basis of homeostasis of the extracellular fluid volume]. Renal, glomerular and tubular, factors responsible for the volume control of extracellular liquid were examined. The part played by angiotensin II in mediating the compensation of this liquid losses was studied in patients with spontaneous polyuria due to diencephalo-posthypophyseal diabetes insipidus or psychogenic polydipsia and healthy subjects with induced hypotonic polyuria. It was noted that: 1) acute expansion elicited a natriuretic response and increased distal sodium load, due to an increase in filtrate and relative inhibition of proximal reabsorption, or proximal inhibition if the filtrate was unchanged. The efficiency of distal sodium transport was often unchanged. 2) Return to sodium balance parity during prolonged expansion of volume, was accomplished by varying renal means, in accordance with the experimental model employed. Distal reabsorption was essentially depressed during prolonged saline load (secondary hypoaldosteronism). When protracted mineralcorticoid treatment was used, however, distal reabsorption was high, even in the escape stage, and its saturation required marked augmentation of the sodium load reaching the distal tubules. 3) Depletion of volume caused by protracted natriuretic treatment in spontaneous polyuria reduced both diuresis and sodium excretion. This resistance to the natriuretic effect of the drug followed intrarenal compensation that reduced the distal sodium load and encouraged reabsorption in some distal sites (secondary hyperaldosteronism). 4) Infusion of angiotensin II in sub- or pauci-pressor doses causes an isosmotic sodium saving, since it reduced the glomerular filtrate and increases the fraction of filtrate reabsorbed by the proximal tubules; the tubular effect is likely secondary to increased vascular, especially postglomerular resistance. In the healthy subject, angiotensin II leads to antidiuresis referable, on account of its intensity and longer time cycle, to ADH release angiotensin-dependent."}
{"id": "PMID:234605", "title": "A study of fetal heart rate deceleration areas. II. Correlation between deceleration areas and fetal pH during labor.", "content": "Three FHR deceleration areas of fixed durations related to the onset of the concomitant uterine contraction were evaluated automatically with a small digital computer during labor. The correlations between these areas and the fetal scalp blood pH values were studied. The deceleration occurring 80 to 140 seconds after the onset of each uterine contraction during the 20 minutes preceding the fetal blood sampling presented the best correlation (r equals minus 0.453) with fetal pH values. In addition to FHR deceleration area, baseline FHR variability should be considered in predicting fetal condition.", "contents": "A study of fetal heart rate deceleration areas. II. Correlation between deceleration areas and fetal pH during labor. Three FHR deceleration areas of fixed durations related to the onset of the concomitant uterine contraction were evaluated automatically with a small digital computer during labor. The correlations between these areas and the fetal scalp blood pH values were studied. The deceleration occurring 80 to 140 seconds after the onset of each uterine contraction during the 20 minutes preceding the fetal blood sampling presented the best correlation (r equals minus 0.453) with fetal pH values. In addition to FHR deceleration area, baseline FHR variability should be considered in predicting fetal condition."}
{"id": "PMID:234608", "title": "Dependence of 2,3-DPG and oxygen affinity of haemoglobin on sex and pregnancy in the guinea-pig.", "content": "Oxygen half-saturation of blood (P50), 2,3-diphosphoglycerate concentration (2,3-DPG) and Bohr effect were determined in male, and nonpregnant and pregnant female guinea pigs, according to a randomized block design. P50 was significantly higher in the female group (26.3 Torr plus or minus 0.22 SEM) than in the male group (24.8 Torr plus or minus 0.26 SEM) and was significantly lower in both these groups than in the pregnant group (27 Torr plus or minus 0.35 SEM). This difference in oxygen affinity was explained by differences in 2,3-DPG: 1.08 plus or minus 0.02 SEM in males, 1.24 plus or minus 0.03 in non-pregnant females and 1.34 plus or minus 0.03 mol/mol HB in pregnant females P50, 2,3-DPG and haemoglobin concentrations were significantly correlated for the ensemble of the 3 groups. There was no significant difference in Bohr effect between the 3 groups.", "contents": "Dependence of 2,3-DPG and oxygen affinity of haemoglobin on sex and pregnancy in the guinea-pig. Oxygen half-saturation of blood (P50), 2,3-diphosphoglycerate concentration (2,3-DPG) and Bohr effect were determined in male, and nonpregnant and pregnant female guinea pigs, according to a randomized block design. P50 was significantly higher in the female group (26.3 Torr plus or minus 0.22 SEM) than in the male group (24.8 Torr plus or minus 0.26 SEM) and was significantly lower in both these groups than in the pregnant group (27 Torr plus or minus 0.35 SEM). This difference in oxygen affinity was explained by differences in 2,3-DPG: 1.08 plus or minus 0.02 SEM in males, 1.24 plus or minus 0.03 in non-pregnant females and 1.34 plus or minus 0.03 mol/mol HB in pregnant females P50, 2,3-DPG and haemoglobin concentrations were significantly correlated for the ensemble of the 3 groups. There was no significant difference in Bohr effect between the 3 groups."}
{"id": "PMID:234610", "title": "The renal plasma flow and glomerular filtration rate as estimated through double radiocompound renography.", "content": "In order to estimate the renal plasma flow and glomerular filtration rate during the course of renography, a method was developed using simultaneously 131I Hippuran and 169Yb DTPA. First results obtained in a survey of approximately 200 patients are encouraging. The method permits an accurate evaluation of the renal function. In addition, by comparing the clearance rate of the two radiocompounds one can also obtain some interesting diagnostic information which can contribute usefully to the interpretation of renographic tracings and/or gamma camera sequential images.", "contents": "The renal plasma flow and glomerular filtration rate as estimated through double radiocompound renography. In order to estimate the renal plasma flow and glomerular filtration rate during the course of renography, a method was developed using simultaneously 131I Hippuran and 169Yb DTPA. First results obtained in a survey of approximately 200 patients are encouraging. The method permits an accurate evaluation of the renal function. In addition, by comparing the clearance rate of the two radiocompounds one can also obtain some interesting diagnostic information which can contribute usefully to the interpretation of renographic tracings and/or gamma camera sequential images."}
{"id": "PMID:234611", "title": "99mTc-DTPA(Sn) dry-kit preparation. Quality control and clearance studies.", "content": "The preparation technique for 99m-Tc-DTPA(Sn)-complex has been studied in detail in order to find the optimal conditions for preparation. The concentration of DTPA should be at least 10 mM, and that of Sn(II) less than 1 mM, in order to obtain a reproducible high-labelling yield. A dry sterile kit was prepared of 39.3 mg H-5DTPA and 2.3 mg SnCl-2 with 2H-2O in a 10 ml vial. The 99m-Tc-DTPA(Sn) was prepared by adding the 99m-Tc-eluate to the vial. After 1 min the solution was sterile-filtered and was ready for use. The plasma clearance of 99m-Tc-DTPA(Sn) in man determined by blood-sampling up to 200 minutes after administration shows a good correlation to endogenous creatinine clearance (r plus 0.93). The plasma disappearance curve studied during 24 h is, however, a sum of three exponentials corresponding to biological half-times of 18 plus or minus 8 min, 105 plus or minus 9 min and 17 plus or minus 4 h. The slow third component representing about 2% is assumed to be due to binding of 99m-Tc to plasma proteins. The absorbed radiation dose calculated for whole body is 8 mrad/mCi, kidneys 50 mrad/mCi, bladder 300 mrad/mCi, ovaries 17 mrad/mCi and testes 11 mrad/mCi. This agent is a valuable radiopharmaceutical for renovascular clinical problems. Scintigraphic imaging of the aorta, kidneys, ureters and bladder (for residual urinary volume-determination) could be performed.", "contents": "99mTc-DTPA(Sn) dry-kit preparation. Quality control and clearance studies. The preparation technique for 99m-Tc-DTPA(Sn)-complex has been studied in detail in order to find the optimal conditions for preparation. The concentration of DTPA should be at least 10 mM, and that of Sn(II) less than 1 mM, in order to obtain a reproducible high-labelling yield. A dry sterile kit was prepared of 39.3 mg H-5DTPA and 2.3 mg SnCl-2 with 2H-2O in a 10 ml vial. The 99m-Tc-DTPA(Sn) was prepared by adding the 99m-Tc-eluate to the vial. After 1 min the solution was sterile-filtered and was ready for use. The plasma clearance of 99m-Tc-DTPA(Sn) in man determined by blood-sampling up to 200 minutes after administration shows a good correlation to endogenous creatinine clearance (r plus 0.93). The plasma disappearance curve studied during 24 h is, however, a sum of three exponentials corresponding to biological half-times of 18 plus or minus 8 min, 105 plus or minus 9 min and 17 plus or minus 4 h. The slow third component representing about 2% is assumed to be due to binding of 99m-Tc to plasma proteins. The absorbed radiation dose calculated for whole body is 8 mrad/mCi, kidneys 50 mrad/mCi, bladder 300 mrad/mCi, ovaries 17 mrad/mCi and testes 11 mrad/mCi. This agent is a valuable radiopharmaceutical for renovascular clinical problems. Scintigraphic imaging of the aorta, kidneys, ureters and bladder (for residual urinary volume-determination) could be performed."}
{"id": "PMID:234622", "title": "A physiological analysis of walking in the American lobster (Homarus americanus).", "content": "The normal, unrestrained, forward walking of the lobster was studied with a closed-circuit television system and a video-tape recorder. A frame-by-frame analysis was undertaken and measurements made of unilateral stepping sequences, contralateral and ipsilateral phase relations between pairs of legs, the movements at the leg joints primarily involved in stepping and their differences in each of the four pereiopods. The order of stepping was expressed in terms of the probability of any leg following any other leg and it was found that while there is a preferred order, there is considerable variation from the dominant pattern. The commonest deviations from the dominant gait are those involving the simplest types of re-ordering of the sequence. Pairs of contralateral legs show a strong tendency to alternate but all phase relations can occur. Similarly, while the ipsilateral legs show preferred phase relations, all possible relations do occur. The four pereiopods from anterior to posterior were found to have respectively, a pulling action, a combined pulling and rowing action, a rowing action and a combined pushing and rowing action. The same parameters of stepping were recorded from animals walking on a transparent, driven treadmill and, as no significant differences were found in comparisons with results from freely moving animals, subsequent results were obtained from animals walking on the treadmill where more detailed study and manipulation could readily be made. The stepping action of the third pereiopod during forwards walking involves major movements about two joints whereas the other pereiopods move about three joints. Detailed study of the intra-leg activity was therefore confined to the third pereiopod where the simpler action considerably simplified the problems involved in collecting and analysing data. Measurements were made of the angles swept out by the joints of the third pereiopod during movement. Electromyograms were recorded from the six muscles primarily responsible for these movements and from movement transducers placed at the joints. The duration of the movements and of the bursts of acitivity in the muscles and the interrelation between different muscle bursts were measured and a computer-aided analysis made to determine the characteristic features of the inter-burst relations during stepping. While there is considerable variability from step to step, the overall activity is relatively phase-constant over a wide range of stepping frequencies. When some of the key parameters of normal walking had been characterized, changes designed to alter the sensory input to the system were imposed.", "contents": "A physiological analysis of walking in the American lobster (Homarus americanus). The normal, unrestrained, forward walking of the lobster was studied with a closed-circuit television system and a video-tape recorder. A frame-by-frame analysis was undertaken and measurements made of unilateral stepping sequences, contralateral and ipsilateral phase relations between pairs of legs, the movements at the leg joints primarily involved in stepping and their differences in each of the four pereiopods. The order of stepping was expressed in terms of the probability of any leg following any other leg and it was found that while there is a preferred order, there is considerable variation from the dominant pattern. The commonest deviations from the dominant gait are those involving the simplest types of re-ordering of the sequence. Pairs of contralateral legs show a strong tendency to alternate but all phase relations can occur. Similarly, while the ipsilateral legs show preferred phase relations, all possible relations do occur. The four pereiopods from anterior to posterior were found to have respectively, a pulling action, a combined pulling and rowing action, a rowing action and a combined pushing and rowing action. The same parameters of stepping were recorded from animals walking on a transparent, driven treadmill and, as no significant differences were found in comparisons with results from freely moving animals, subsequent results were obtained from animals walking on the treadmill where more detailed study and manipulation could readily be made. The stepping action of the third pereiopod during forwards walking involves major movements about two joints whereas the other pereiopods move about three joints. Detailed study of the intra-leg activity was therefore confined to the third pereiopod where the simpler action considerably simplified the problems involved in collecting and analysing data. Measurements were made of the angles swept out by the joints of the third pereiopod during movement. Electromyograms were recorded from the six muscles primarily responsible for these movements and from movement transducers placed at the joints. The duration of the movements and of the bursts of acitivity in the muscles and the interrelation between different muscle bursts were measured and a computer-aided analysis made to determine the characteristic features of the inter-burst relations during stepping. While there is considerable variability from step to step, the overall activity is relatively phase-constant over a wide range of stepping frequencies. When some of the key parameters of normal walking had been characterized, changes designed to alter the sensory input to the system were imposed."}
{"id": "PMID:234627", "title": "Tryptoline formation by a preparation from brain with 5-methyltetrahydrofolic acid and tryptamine.", "content": "An enzymatic preparation from human brain converts tryptamine to tryptoline (9H-1,2,3,4-tetrahydropyrido[3,4-b]indole) in the presence of 5-methyltetrahydrofolic acid. Similarly, N-methyltryptamine and 5-hydroxytryptamine yield 1-methyltryptoline and 5-hydroxytryptoline, respectively. Neither in vitro nor in vivo formation of these compounds by human tissues has been described.", "contents": "Tryptoline formation by a preparation from brain with 5-methyltetrahydrofolic acid and tryptamine. An enzymatic preparation from human brain converts tryptamine to tryptoline (9H-1,2,3,4-tetrahydropyrido[3,4-b]indole) in the presence of 5-methyltetrahydrofolic acid. Similarly, N-methyltryptamine and 5-hydroxytryptamine yield 1-methyltryptoline and 5-hydroxytryptoline, respectively. Neither in vitro nor in vivo formation of these compounds by human tissues has been described."}
{"id": "PMID:234633", "title": "The influence of body position on pulmonary function in low birthweight babies.", "content": "The influence of the prone and supine body positions on the respiratory rate, arterial pH, pO2, pCO2 and serum bicarbonate level; on alveolar pO2 and pCO2; and on alveolar/arterial gradients for carbon dioxide and oxygen, were compared in 10 low birthweight infants. THE ALveolar pCO2 was higher in the prone, while pO2 was higher in the supine position, possibly as a result of ventilation/perfusion imbalance with increased physiological dead space in the supine position. There were no significant differences between the other parameters studied. Since aspiration of feed by the low birthweight infant is a major cause of morbidity and mortality, evidence is presented in favour of the prone nursing position.", "contents": "The influence of body position on pulmonary function in low birthweight babies. The influence of the prone and supine body positions on the respiratory rate, arterial pH, pO2, pCO2 and serum bicarbonate level; on alveolar pO2 and pCO2; and on alveolar/arterial gradients for carbon dioxide and oxygen, were compared in 10 low birthweight infants. THE ALveolar pCO2 was higher in the prone, while pO2 was higher in the supine position, possibly as a result of ventilation/perfusion imbalance with increased physiological dead space in the supine position. There were no significant differences between the other parameters studied. Since aspiration of feed by the low birthweight infant is a major cause of morbidity and mortality, evidence is presented in favour of the prone nursing position."}
{"id": "PMID:234643", "title": "[Fibrin (ogen) Split products of nephropathies].", "content": "On healthy individuals fibrin(ogen) split products cannot be demonstrated in the blood. Catabolic products of fibrin and fibrinogen appear in the blood in case of general fibrinolysis, consumption coagulopathy with secondary fibrinolysis as well as local fibrin films with secondary fibrinolysis. The regular routine determination of fibrin(ogen) split products in serum or urine may indicate starting complications of many diseases. The appearance of these split products in case of renal affections indicates acute and active processes on the kidneys themselves; fibrin films appear in case of acute and chronic glomerulonephritis, casting-off crises on renal transplants, EPH gestosis, renal phlebothrombosis, hemolytic-uremic syndrom and occasionally urinary tract infections. The demonstration of fibrin(ogen) split products in serum or urine allows the following conclusions: a) acute and active process on the kidneys themselves; b) HMWS in urine indicate a fibrin film in the kidneys; c) an immediate beginning of an anticoagulation therapy; d) good possibilities to judge the therapeutic effect and by this the further progress of disease.", "contents": "[Fibrin (ogen) Split products of nephropathies]. On healthy individuals fibrin(ogen) split products cannot be demonstrated in the blood. Catabolic products of fibrin and fibrinogen appear in the blood in case of general fibrinolysis, consumption coagulopathy with secondary fibrinolysis as well as local fibrin films with secondary fibrinolysis. The regular routine determination of fibrin(ogen) split products in serum or urine may indicate starting complications of many diseases. The appearance of these split products in case of renal affections indicates acute and active processes on the kidneys themselves; fibrin films appear in case of acute and chronic glomerulonephritis, casting-off crises on renal transplants, EPH gestosis, renal phlebothrombosis, hemolytic-uremic syndrom and occasionally urinary tract infections. The demonstration of fibrin(ogen) split products in serum or urine allows the following conclusions: a) acute and active process on the kidneys themselves; b) HMWS in urine indicate a fibrin film in the kidneys; c) an immediate beginning of an anticoagulation therapy; d) good possibilities to judge the therapeutic effect and by this the further progress of disease."}
{"id": "PMID:234644", "title": "[Continuous irrigation of the bladder with acetic acid solution and its therapeutic effect on candida-infection].", "content": "Our clinical experience with acetic acid solution in the treatment of candida infection of the bladder was confirmed by in vitro experiments. We apply continuous bladder irrigation with increasing concentrations of acetic acid solution up to pH 5.0. The majority of patients had received antibiotics or cytostatic drugs and suffered from chronic and malignant diseases. A case report is given with endoscopic documentation of the influence of acetic acid solution on the bladder.", "contents": "[Continuous irrigation of the bladder with acetic acid solution and its therapeutic effect on candida-infection]. Our clinical experience with acetic acid solution in the treatment of candida infection of the bladder was confirmed by in vitro experiments. We apply continuous bladder irrigation with increasing concentrations of acetic acid solution up to pH 5.0. The majority of patients had received antibiotics or cytostatic drugs and suffered from chronic and malignant diseases. A case report is given with endoscopic documentation of the influence of acetic acid solution on the bladder."}
{"id": "PMID:234646", "title": "Renal calculi and biochemical abnormalities. In children with myelomeningocele and heoconduit diversion.", "content": "Of 38 pediatric cases of ileoconduit urinary diversion of myelomeningocele, 4 with renal calculi are presented. An increased risk of renal calculus formation may be imposed on children with myelomeningocele with ileoconduit urinary diversion especially so in functionally and anatomically abnormal kidneys and in chronic renal infection with urea-splitting bacteria. It is not clear why the ileoconduit procedure should increase the incidence of renal calculi in such children.", "contents": "Renal calculi and biochemical abnormalities. In children with myelomeningocele and heoconduit diversion. Of 38 pediatric cases of ileoconduit urinary diversion of myelomeningocele, 4 with renal calculi are presented. An increased risk of renal calculus formation may be imposed on children with myelomeningocele with ileoconduit urinary diversion especially so in functionally and anatomically abnormal kidneys and in chronic renal infection with urea-splitting bacteria. It is not clear why the ileoconduit procedure should increase the incidence of renal calculi in such children."}
{"id": "PMID:234648", "title": "Response of rat testis to localized induced hyperthermia.", "content": "A method is presented in which the rat testis is extensively mobilized through a low abdominal incision, but in which its blood supply is carefully preserved. Localized hyperthermia is induced in this mobilized testis by water bath immersion. The tissue temperature is measured during and after immersion by means of a thermocouple inserted into the tissue. The relative sensitivity of spermatogenic tissue to increased temperature is confirmed and the relative resistance of Sertoli and Leydig cells is noted. Minimal or absent inflammatory reaction to thermal destruction of testicular cells is found as long as the tubule is intact. A marked peritesticular inflammatory response is noted when the total testicular tissue is destroyed at the highest temperature tested.", "contents": "Response of rat testis to localized induced hyperthermia. A method is presented in which the rat testis is extensively mobilized through a low abdominal incision, but in which its blood supply is carefully preserved. Localized hyperthermia is induced in this mobilized testis by water bath immersion. The tissue temperature is measured during and after immersion by means of a thermocouple inserted into the tissue. The relative sensitivity of spermatogenic tissue to increased temperature is confirmed and the relative resistance of Sertoli and Leydig cells is noted. Minimal or absent inflammatory reaction to thermal destruction of testicular cells is found as long as the tubule is intact. A marked peritesticular inflammatory response is noted when the total testicular tissue is destroyed at the highest temperature tested."}
{"id": "PMID:234660", "title": "In vitro hatching of the tapeworm Moniezia expansa (Cestoda: Anoplocephalidae) and some properties of the egg membranes.", "content": "In vitro studies revealed that the hatching of oncospheres of Moniezia expansa requires the mechanical breakage of the eggshell and subshell membrane and enzymic digestion of the pyriform apparatus. Removal of the outer two egg membranes elicits the activation of most oncospheres. Between pH 5.0-7.8, there is no significant difference in numbers of oncospheres activated by eggshell removal and the addition of sodium bicarbonate has no effect. Solutions of more extreme pH values (2.0 and 10.0) are harmful and render oncospheres immobile. The subshell membrane forms a barrier to the passage of water in an osmotic gradient and to several molecular and ionic substances. Between the eggshell and subshell membrane is a layer of droplets which have a strong affinity for Sudan stains and which are partially removed by lipase. The eggshell is resistant to a variety of proteolytic enzymes, amylases and lipase. The pyriform apparatus is digested by chymotrypsin and pepsin, though not by trypsin. Both eggshell and pyriform apparatus are dissolved by solutions of sodium sulphide and sodium hypochlorite, indicating that their structures are stabilized by disulphide bonds and other covalent linkages.", "contents": "In vitro hatching of the tapeworm Moniezia expansa (Cestoda: Anoplocephalidae) and some properties of the egg membranes. In vitro studies revealed that the hatching of oncospheres of Moniezia expansa requires the mechanical breakage of the eggshell and subshell membrane and enzymic digestion of the pyriform apparatus. Removal of the outer two egg membranes elicits the activation of most oncospheres. Between pH 5.0-7.8, there is no significant difference in numbers of oncospheres activated by eggshell removal and the addition of sodium bicarbonate has no effect. Solutions of more extreme pH values (2.0 and 10.0) are harmful and render oncospheres immobile. The subshell membrane forms a barrier to the passage of water in an osmotic gradient and to several molecular and ionic substances. Between the eggshell and subshell membrane is a layer of droplets which have a strong affinity for Sudan stains and which are partially removed by lipase. The eggshell is resistant to a variety of proteolytic enzymes, amylases and lipase. The pyriform apparatus is digested by chymotrypsin and pepsin, though not by trypsin. Both eggshell and pyriform apparatus are dissolved by solutions of sodium sulphide and sodium hypochlorite, indicating that their structures are stabilized by disulphide bonds and other covalent linkages."}
{"id": "PMID:234661", "title": "Follicular and luteal function in the puberal rat: gonadotrophic hormone stimulation and enzymic-nucleotide interactions.", "content": "Using the puberal rat and the PMS-treated rat as animal systems, ovarian events associated with follicular and luteal development have been characterized by measuring gonadotrophic hormone (LH, FSH and prolactin) and progesterone concentrations in peripheral serum; and selected enzymic (NAD-kinase:NAD-K and glucose-6-phosphate dehydrogenase: G6PD) activities and nucleotide (NAD, NADH, NADP, NADPH, ATP) concentrations in ovarian tissue. In the puberal rat, the period of follicular development was characterized by increased ovarian NAD-K SA, NAD and NADH concentrations and decreased ATP and NADP concentrations. The first pro-oestrus was characterized by greatly elevated LH, FSH, prolactin and progesterone concentrations, significant decreases in ovarian NAD-K SA, NAD, NADP and ATP concentrations, and an increase in NADPH concentrations. The development of new corpora lutea was associated with striking increases in ovarian NAD-K SA and G6PD SA. Increased activity of both enzymes exhibited a significant positive coefficient of correlation with the number of corpora lutea contained within the ovarian tissue. PMS (4 IU) stimulation of follicular activity resulted in events leading to the induction of an endogenous LH surge and ovulation. Associated with increased follicular activity was increased ovarian NAD-K SA. In contrast to the puberal rat, no rise in progesterone concentrations was associated with the LH surge or the formation of corpora lutea.", "contents": "Follicular and luteal function in the puberal rat: gonadotrophic hormone stimulation and enzymic-nucleotide interactions. Using the puberal rat and the PMS-treated rat as animal systems, ovarian events associated with follicular and luteal development have been characterized by measuring gonadotrophic hormone (LH, FSH and prolactin) and progesterone concentrations in peripheral serum; and selected enzymic (NAD-kinase:NAD-K and glucose-6-phosphate dehydrogenase: G6PD) activities and nucleotide (NAD, NADH, NADP, NADPH, ATP) concentrations in ovarian tissue. In the puberal rat, the period of follicular development was characterized by increased ovarian NAD-K SA, NAD and NADH concentrations and decreased ATP and NADP concentrations. The first pro-oestrus was characterized by greatly elevated LH, FSH, prolactin and progesterone concentrations, significant decreases in ovarian NAD-K SA, NAD, NADP and ATP concentrations, and an increase in NADPH concentrations. The development of new corpora lutea was associated with striking increases in ovarian NAD-K SA and G6PD SA. Increased activity of both enzymes exhibited a significant positive coefficient of correlation with the number of corpora lutea contained within the ovarian tissue. PMS (4 IU) stimulation of follicular activity resulted in events leading to the induction of an endogenous LH surge and ovulation. Associated with increased follicular activity was increased ovarian NAD-K SA. In contrast to the puberal rat, no rise in progesterone concentrations was associated with the LH surge or the formation of corpora lutea."}
{"id": "PMID:234662", "title": "Hormone and enzyme assays in pregnancy. V. A rapid method for measuring the placental cystine-aminopeptidase using 1-cystine-bis-1-cystine-bis-p-nitroanilide-nitroanilide as substrate.", "content": "A rapid and simple method for determination of the placental cystine-aminopeptidase (P-CAP) activity in plasma is presented. The enzyme-catalysed hydrolysis of the substrate, 1-cystine-bis-p-nitroanilide, is followed in a spectrophotometer by reading the absorbance of the product p-nitroaniline at 380 nm. The absorbance increases linearily with time after a lag-period of 30 seconds to 5 min. The reaction is followed for about 10 min and the increase in absorbtion per min is calculated from the linear part of the absorbtion curve. The test could also be performed by taking 2 readings at about 5 min intervals. In the studies of the enzyme kinetics a competitive inhibitor of the reaction was found in plasma. The amount of the inhibitory substances seemed to be nearly constant in the plasma samples studied from normal pregnant women as well as in plasma samples with high enzyme activity (twin-pregnancy) and low enzyme activity (severe pre-eclampsia). The normal enzyme activity pattern showed an increase from about 210 days of pregnancy and towards the term. A coefficient of correlation of plus 0.83 with the more time consuming method using 1-cystine-di-beta-naphtylamide as substrate was found. It was concluded that the present method could replace the method described by Babuna & Yenen (1966) at least from about 210 days of pregnancy and where a rapid answer is necessary.", "contents": "Hormone and enzyme assays in pregnancy. V. A rapid method for measuring the placental cystine-aminopeptidase using 1-cystine-bis-1-cystine-bis-p-nitroanilide-nitroanilide as substrate. A rapid and simple method for determination of the placental cystine-aminopeptidase (P-CAP) activity in plasma is presented. The enzyme-catalysed hydrolysis of the substrate, 1-cystine-bis-p-nitroanilide, is followed in a spectrophotometer by reading the absorbance of the product p-nitroaniline at 380 nm. The absorbance increases linearily with time after a lag-period of 30 seconds to 5 min. The reaction is followed for about 10 min and the increase in absorbtion per min is calculated from the linear part of the absorbtion curve. The test could also be performed by taking 2 readings at about 5 min intervals. In the studies of the enzyme kinetics a competitive inhibitor of the reaction was found in plasma. The amount of the inhibitory substances seemed to be nearly constant in the plasma samples studied from normal pregnant women as well as in plasma samples with high enzyme activity (twin-pregnancy) and low enzyme activity (severe pre-eclampsia). The normal enzyme activity pattern showed an increase from about 210 days of pregnancy and towards the term. A coefficient of correlation of plus 0.83 with the more time consuming method using 1-cystine-di-beta-naphtylamide as substrate was found. It was concluded that the present method could replace the method described by Babuna & Yenen (1966) at least from about 210 days of pregnancy and where a rapid answer is necessary."}
{"id": "PMID:234663", "title": "Glycosidases in human skin fibroblast cultures. Alpha-fucosidase, alpha-galactosidase, alpha-glucosidase, beta-mannosidase, and N-acetyl-alpha-glucosaminidase.", "content": "Five glycosidases, alpha-fucosidase, alpha-galactosidase, alpha-glucosidase, beta-mannosidase and N-acetyl-alpha-glucosaminidase were studied in human skin fibroblast cultures. The pH-dependency, kinetic properties of the enzymes and results of isoelectric focusing and ion exchange chromatography are presented. Techniques suitable for diagnosing inborn lysosomal diseases in skin fibroblast cultures are defined.", "contents": "Glycosidases in human skin fibroblast cultures. Alpha-fucosidase, alpha-galactosidase, alpha-glucosidase, beta-mannosidase, and N-acetyl-alpha-glucosaminidase. Five glycosidases, alpha-fucosidase, alpha-galactosidase, alpha-glucosidase, beta-mannosidase and N-acetyl-alpha-glucosaminidase were studied in human skin fibroblast cultures. The pH-dependency, kinetic properties of the enzymes and results of isoelectric focusing and ion exchange chromatography are presented. Techniques suitable for diagnosing inborn lysosomal diseases in skin fibroblast cultures are defined."}
{"id": "PMID:234665", "title": "Arrhythmias following cardiac surgery: relation to serum digoxin levels.", "content": "Arrhythmias were analyzed in 50 patients undergoing cardiac surgery: 27 with valve surgery, 15 with coronary artery bypass (CAB), 5 with CAB and valve surgery, and 3 with miscellaneous procedures. The role of electrolyte abnormalities, pericarditis, serum osmolarity, digoxin level, and the type of surgery performed was evaluated. Thirty-seven out of 50 patients (74 per cent) had a postoperative arrhythmia, and a total of 78 different arrhythmias were noted. Twenty-six out of 27 patients with valve surgery had an arrhythmia vs. six out of 15 patients with CAB (p less than 0.001). Atrial fibrillation was the most common arrhythmia in all groups. Although postoperative hypocalcemia, hypomagnesemia, pericarditis, and wide shifts in osmolarity were common, they did not correlate with arrhythmias. Seventeen patients developed postoperative arrhythmias compatible with digitalis toxicity, including junctional rhythm, atrioventricular dissociation, or atrial tachycardia with block. However, the range of serum digoxin levels in these patients was zero to 2.80 ng. per milliliter. This suggests increased sensitivity to digitalis glycosides or the effects of surgical trauma as the etiology of arrhythmia in many patients. The distinction between digitalis-induced arrhythmia and spontaneously occurring arrhythmia cannot be made with certainty in most postoperative patients. Therapy should reflect an awareness of the potential for postoperative digitoxicity.", "contents": "Arrhythmias following cardiac surgery: relation to serum digoxin levels. Arrhythmias were analyzed in 50 patients undergoing cardiac surgery: 27 with valve surgery, 15 with coronary artery bypass (CAB), 5 with CAB and valve surgery, and 3 with miscellaneous procedures. The role of electrolyte abnormalities, pericarditis, serum osmolarity, digoxin level, and the type of surgery performed was evaluated. Thirty-seven out of 50 patients (74 per cent) had a postoperative arrhythmia, and a total of 78 different arrhythmias were noted. Twenty-six out of 27 patients with valve surgery had an arrhythmia vs. six out of 15 patients with CAB (p less than 0.001). Atrial fibrillation was the most common arrhythmia in all groups. Although postoperative hypocalcemia, hypomagnesemia, pericarditis, and wide shifts in osmolarity were common, they did not correlate with arrhythmias. Seventeen patients developed postoperative arrhythmias compatible with digitalis toxicity, including junctional rhythm, atrioventricular dissociation, or atrial tachycardia with block. However, the range of serum digoxin levels in these patients was zero to 2.80 ng. per milliliter. This suggests increased sensitivity to digitalis glycosides or the effects of surgical trauma as the etiology of arrhythmia in many patients. The distinction between digitalis-induced arrhythmia and spontaneously occurring arrhythmia cannot be made with certainty in most postoperative patients. Therapy should reflect an awareness of the potential for postoperative digitoxicity."}
{"id": "PMID:234666", "title": "Angiotensin- and norepinephrine-induced myocardial lesions: experimental and clinical studies in rabbits and man.", "content": "The ability of large doses of exogenous angiotensin II to cause widespread multifocal microscopic myocardial necrosis in the rabbit has been confirmed. Angiotensin II also consistently produced acute renal failure with, less consistently, renal tubular necrosis. Norepinephrine infusions caused histologically indistinguishable myocardial lesions, but did not detectably affect renal function or histology. Severe renal failure, induced by bilateral nephrectomy (with or without concurrent glycerol administration) was not associated with similar cardiac lesions. Acute renal failure of comparable or greater severity to that induced by angiotensin II was produced by intramuscular cephaloridine, and was not associated with cardiac lesions. Rabbits infused with saline intravenously or \"sham\"-operated by simply opening and closing the peritoneal cavity did not develop renal failure and showed no cardiac or renal lesions histologically. Myocardial lesions, apparently identical to those seen in the rabbits, were observed postmortem in three patients known to have had high circulating levels of angiotensin II before death, although in all three cases alternative explanations are possible. Unexplained arrhythmia, cardiac arrest, and central chest pain without clear cardiographic or serum enzyme evidence of myocardial infarction occurred in two other subjects with very high plasma levels of angiotensin II. These attacks ceased after bilateral nephrectomy and a consequent fall in plasma angiotensin II. The cardiac attacks in these five patients all occurred during or shortly after procedures, such as sodium-depleting dialysis, renal artery surgery, or diazoxide administration, known to cause increase in plasma concentrations of renin and angiotensin II.", "contents": "Angiotensin- and norepinephrine-induced myocardial lesions: experimental and clinical studies in rabbits and man. The ability of large doses of exogenous angiotensin II to cause widespread multifocal microscopic myocardial necrosis in the rabbit has been confirmed. Angiotensin II also consistently produced acute renal failure with, less consistently, renal tubular necrosis. Norepinephrine infusions caused histologically indistinguishable myocardial lesions, but did not detectably affect renal function or histology. Severe renal failure, induced by bilateral nephrectomy (with or without concurrent glycerol administration) was not associated with similar cardiac lesions. Acute renal failure of comparable or greater severity to that induced by angiotensin II was produced by intramuscular cephaloridine, and was not associated with cardiac lesions. Rabbits infused with saline intravenously or \"sham\"-operated by simply opening and closing the peritoneal cavity did not develop renal failure and showed no cardiac or renal lesions histologically. Myocardial lesions, apparently identical to those seen in the rabbits, were observed postmortem in three patients known to have had high circulating levels of angiotensin II before death, although in all three cases alternative explanations are possible. Unexplained arrhythmia, cardiac arrest, and central chest pain without clear cardiographic or serum enzyme evidence of myocardial infarction occurred in two other subjects with very high plasma levels of angiotensin II. These attacks ceased after bilateral nephrectomy and a consequent fall in plasma angiotensin II. The cardiac attacks in these five patients all occurred during or shortly after procedures, such as sodium-depleting dialysis, renal artery surgery, or diazoxide administration, known to cause increase in plasma concentrations of renin and angiotensin II."}
{"id": "PMID:234667", "title": "The long Q-T syndrome.", "content": "Recent clinical and experimental data on the long Q-T syndrome (LQTS) are presented and discussed. The pathogenesis of LQTS is dependent on an imbalance between various components of the cardiac sympathetic innervation. A congenital decreased activity through the right cardiac sympathetic nerves seems to be the more likely pathogenetic mechanism for the majority of cases. Other forms of sympathetic imbalance, including left or even right hyperactivity, are, however, possible in isolated cases. Beta-blockers, at full blocking dose, represent the therapy of choice and are greatly effective in reducing the mortality (from 73 per cent to 6 per cent). If syncopal attacks are not eliminated by the medical therapy, the the ablation of the left stellate ganglion along with the first thoracic ganglia is the most rational and specific therapy. The possiblity for the correctly diagnosed and treated patients to escape an otherwise impending death calls urgently for diffusion of the knowledge about the long Q-T syndrome.", "contents": "The long Q-T syndrome. Recent clinical and experimental data on the long Q-T syndrome (LQTS) are presented and discussed. The pathogenesis of LQTS is dependent on an imbalance between various components of the cardiac sympathetic innervation. A congenital decreased activity through the right cardiac sympathetic nerves seems to be the more likely pathogenetic mechanism for the majority of cases. Other forms of sympathetic imbalance, including left or even right hyperactivity, are, however, possible in isolated cases. Beta-blockers, at full blocking dose, represent the therapy of choice and are greatly effective in reducing the mortality (from 73 per cent to 6 per cent). If syncopal attacks are not eliminated by the medical therapy, the the ablation of the left stellate ganglion along with the first thoracic ganglia is the most rational and specific therapy. The possiblity for the correctly diagnosed and treated patients to escape an otherwise impending death calls urgently for diffusion of the knowledge about the long Q-T syndrome."}
{"id": "PMID:234668", "title": "A comparison of timolol and propranolol in essential hypertension.", "content": "The antihypertensive efficacy of a new beta-adrenergic receptor inhibiting compound, timolol (MK-950), was evaluated using two treatment protocols: double-blind timolol vs. placebo treatment and double-blind timolol vs. propranolol (10 and 12 patients, respectively). These studies indicate that timolol significantly and safely reduced arterial pressure in mild to moderately severe essential hypertensive patients. The reduction in mean arterial pressure with timolol was equivalent to the pressure reduction with propranolol when the doses of 30 and 120 mg. per day, respectively, were used.", "contents": "A comparison of timolol and propranolol in essential hypertension. The antihypertensive efficacy of a new beta-adrenergic receptor inhibiting compound, timolol (MK-950), was evaluated using two treatment protocols: double-blind timolol vs. placebo treatment and double-blind timolol vs. propranolol (10 and 12 patients, respectively). These studies indicate that timolol significantly and safely reduced arterial pressure in mild to moderately severe essential hypertensive patients. The reduction in mean arterial pressure with timolol was equivalent to the pressure reduction with propranolol when the doses of 30 and 120 mg. per day, respectively, were used."}
{"id": "PMID:234669", "title": "Effects of aminophylline on the threshold for initiating ventricular fibrillation during respiratory failure.", "content": "Cardiac arrhythmias have frequently been reported in association with respiratory failure. The possible additive role of pharmacologic agents in precipitating cardiac disturbances in patients with respiratory failure has only recently been emphasized. The effects of aminophylline on the ventricular fibrillation threshold during normal acid-base conditions and during respiratory failure were studied in anesthetized open chest dogs. The ventricular fibrillation threshold was measured by passing a gated train of 12 constant current pulses through the ventricular myocardium during the vulnerable period of the cardiac cycle. During the infusion of aminophylline, the ventricular fibrillation threshold was reduced by 30 to 40 percent of the control when pH and partial pressures of oxygen (PO2) and carbon dioxide (CO2) were kept within normal limits. When respiratory failure was produced by hypoventilation (pH 7.05 to 7.25; PC02 70 to 100 mm Hg: P02 20 to 40 mm Hg), infusion of aminophylline resulted in an even greater decrease in ventricular fibrillation threshold to 60 percent of the control level. These experiments suggest that although many factors may contribute to the increased incidence of ventricular arrhythmias in respiratory failure, pharmacologic agents, particularly aminophylline, may play a significant role.", "contents": "Effects of aminophylline on the threshold for initiating ventricular fibrillation during respiratory failure. Cardiac arrhythmias have frequently been reported in association with respiratory failure. The possible additive role of pharmacologic agents in precipitating cardiac disturbances in patients with respiratory failure has only recently been emphasized. The effects of aminophylline on the ventricular fibrillation threshold during normal acid-base conditions and during respiratory failure were studied in anesthetized open chest dogs. The ventricular fibrillation threshold was measured by passing a gated train of 12 constant current pulses through the ventricular myocardium during the vulnerable period of the cardiac cycle. During the infusion of aminophylline, the ventricular fibrillation threshold was reduced by 30 to 40 percent of the control when pH and partial pressures of oxygen (PO2) and carbon dioxide (CO2) were kept within normal limits. When respiratory failure was produced by hypoventilation (pH 7.05 to 7.25; PC02 70 to 100 mm Hg: P02 20 to 40 mm Hg), infusion of aminophylline resulted in an even greater decrease in ventricular fibrillation threshold to 60 percent of the control level. These experiments suggest that although many factors may contribute to the increased incidence of ventricular arrhythmias in respiratory failure, pharmacologic agents, particularly aminophylline, may play a significant role."}
{"id": "PMID:234672", "title": "Serum gamma-glutamyl transpeptidase activity in normal children.", "content": "Serum gamma-glutamyl transpeptidase (GGT) activities of 82 healthy neonates (aged 9 hours to 11 days) and 106 healthy children (aged 2 months to 15 years) were determined. Serum GGT activity of 47 neonates (51%) was higher than the accepted upper limit of normal for adults. By three months of age, all of the children had serum GGT activities that were within the accepted normal range for adults. Thereafter there was only minimal variation in serum GGT activities of older children. Although mean serum GGT activity was higher in male children than in female children, there was no significant difference between the values for male and female neonates. That after the neonatal period serum GGT activity is constant in the adult range and is not affected by bone growth as is alkaline phosphatase suggests that GGT may be of value in the evaluation of hepatobiliary disease in children.", "contents": "Serum gamma-glutamyl transpeptidase activity in normal children. Serum gamma-glutamyl transpeptidase (GGT) activities of 82 healthy neonates (aged 9 hours to 11 days) and 106 healthy children (aged 2 months to 15 years) were determined. Serum GGT activity of 47 neonates (51%) was higher than the accepted upper limit of normal for adults. By three months of age, all of the children had serum GGT activities that were within the accepted normal range for adults. Thereafter there was only minimal variation in serum GGT activities of older children. Although mean serum GGT activity was higher in male children than in female children, there was no significant difference between the values for male and female neonates. That after the neonatal period serum GGT activity is constant in the adult range and is not affected by bone growth as is alkaline phosphatase suggests that GGT may be of value in the evaluation of hepatobiliary disease in children."}
{"id": "PMID:234673", "title": "Redesigned apparatus for anaerobic measurement of blood pH at low temperatures.", "content": "A newly designed apparatus for anaerobic measurement of blood pH at low temperatures is presented. This apparatus features a larger glass electrode surface area, which is necessary to overcome the increased resistance of the glass as blood pH determinations at 0-15 C. are undertaken. Utilization of this equipment has confirmed the deltapH per degree C. of whole blood to be 0.0156, while intracellular pH of blood has a deltapH per degree C. of 0.0165.", "contents": "Redesigned apparatus for anaerobic measurement of blood pH at low temperatures. A newly designed apparatus for anaerobic measurement of blood pH at low temperatures is presented. This apparatus features a larger glass electrode surface area, which is necessary to overcome the increased resistance of the glass as blood pH determinations at 0-15 C. are undertaken. Utilization of this equipment has confirmed the deltapH per degree C. of whole blood to be 0.0156, while intracellular pH of blood has a deltapH per degree C. of 0.0165."}
{"id": "PMID:234674", "title": "Mucosal-cell counts in ulcerative and granulomatous colitis.", "content": "Epithelial and connective-tissue cells were counted in rectal mucosal biopsies from 215 patients with ulcerative colitis, 98 patients with granulomatous colitis, and 50 controls. The results were analyzed statistically. Significantly decreased mucous goblet cells were found both in sigmoidoscopically abnormal ulcerative colitis and in granulomatous colitis, and they increased during the healing process. More pyknotic and karyorrhectic epithelial cells occurred in active ulcerative colitis than in granulomatous colitis. Inactive ulcerative colitis still manifested histologic evidence of acute and chronic inflammation, while sigmoidoscopically normal granulomatous colitis biopsies after previous gross rectal disease showed significantly increased macrophages in the lamina propria. Cell counts were valuable for differential diagnosis after the sigmoidoscopic appearance became normal. The acute inflammation of ulcerative colitis, as indicated by neutrophils, was decreased most notably following therapy with prednisone or 6-mercaptopurine. Chronic inflammation associated with fewer plasma cells was decreased after salicylazosulfapyridine as well as either of the other two drugs; macrophages, indicators of healing, increased most after 6-mercaptopurine combined with another anti-inflammatory agent.", "contents": "Mucosal-cell counts in ulcerative and granulomatous colitis. Epithelial and connective-tissue cells were counted in rectal mucosal biopsies from 215 patients with ulcerative colitis, 98 patients with granulomatous colitis, and 50 controls. The results were analyzed statistically. Significantly decreased mucous goblet cells were found both in sigmoidoscopically abnormal ulcerative colitis and in granulomatous colitis, and they increased during the healing process. More pyknotic and karyorrhectic epithelial cells occurred in active ulcerative colitis than in granulomatous colitis. Inactive ulcerative colitis still manifested histologic evidence of acute and chronic inflammation, while sigmoidoscopically normal granulomatous colitis biopsies after previous gross rectal disease showed significantly increased macrophages in the lamina propria. Cell counts were valuable for differential diagnosis after the sigmoidoscopic appearance became normal. The acute inflammation of ulcerative colitis, as indicated by neutrophils, was decreased most notably following therapy with prednisone or 6-mercaptopurine. Chronic inflammation associated with fewer plasma cells was decreased after salicylazosulfapyridine as well as either of the other two drugs; macrophages, indicators of healing, increased most after 6-mercaptopurine combined with another anti-inflammatory agent."}
{"id": "PMID:234675", "title": "Control factors in the release of gastrin by direct electrical stimulation of the vagus.", "content": "The release of gastrin by direct electrical stimulation of the vagus was studied together with the relative effects on the response of antral and duodenal acidification. As expected, gastrin levels increased to three times the normal simulated response following antral neutralization. In contrast, duodenal acidification failed to influence the vagal release of gastrin when the antrum was neutralized although it had a minor effect when the antrum was acidified. Thus the antral pH dominates over duodenal pH as a factor in controlling gastrin release. Surprisingly, atropine in doses which blocked acid release and produced marked cardiac effects failed to inhibit the release of gastrin from the antrum on vagal stimulation. This suggests that, using this model, vagal release of gastrin, if cholinergic, is highly resistant to atropine.", "contents": "Control factors in the release of gastrin by direct electrical stimulation of the vagus. The release of gastrin by direct electrical stimulation of the vagus was studied together with the relative effects on the response of antral and duodenal acidification. As expected, gastrin levels increased to three times the normal simulated response following antral neutralization. In contrast, duodenal acidification failed to influence the vagal release of gastrin when the antrum was neutralized although it had a minor effect when the antrum was acidified. Thus the antral pH dominates over duodenal pH as a factor in controlling gastrin release. Surprisingly, atropine in doses which blocked acid release and produced marked cardiac effects failed to inhibit the release of gastrin from the antrum on vagal stimulation. This suggests that, using this model, vagal release of gastrin, if cholinergic, is highly resistant to atropine."}
{"id": "PMID:234676", "title": "Renal prostaglandins.", "content": "Relative renal ischemia, produced by a variety of interventions, is modulated or buffered by prostaglandins synthesized within the kidney. These prostaglandins, however, do not account for renal autoregulation in its classic sense. They can facilitate salt and water excretion, largely through effects on physical forces in proximal peritubular capillaries, as evidenced by augmented renal blood flow. Renal prostaglandins may play a role in chronic water balance, but they probably are not important in chronic electrolyte homeostasis. There are several potential mechanisms by which renal prostaglandins could exert antihypertensive efects. Establishment of the importance of these agents, however, as antihypertensive hormones remains a challenge for future investigation.", "contents": "Renal prostaglandins. Relative renal ischemia, produced by a variety of interventions, is modulated or buffered by prostaglandins synthesized within the kidney. These prostaglandins, however, do not account for renal autoregulation in its classic sense. They can facilitate salt and water excretion, largely through effects on physical forces in proximal peritubular capillaries, as evidenced by augmented renal blood flow. Renal prostaglandins may play a role in chronic water balance, but they probably are not important in chronic electrolyte homeostasis. There are several potential mechanisms by which renal prostaglandins could exert antihypertensive efects. Establishment of the importance of these agents, however, as antihypertensive hormones remains a challenge for future investigation."}
{"id": "PMID:234677", "title": "The renin axis and vasoconstriction volume analysis for understanding and treating renovascular and renal hypertension.", "content": "Information defining the renin-angiotension-aldosterone axis as a control system concurrently regulating salt balance and blood pressure has been applied to reexamine the role of renin in experimental and clinical forms of renovascular and renal hypertension, and thence to develop criteria for differentiating these entities. Experimentally, there are two models of renovascular hypertension; one is characterized by excess renin with reduced sodium (vasoconstrictor form) and the other by excess sodium with reduced renin (volume form). But with sodium depletion, the volume form converts to a vasoconstrictor form illustrating how the two factors coordinate to maintain blood pressure. In man, renovascular and renal hypertensions appear to be sustained by the same two mechanisms. Studies in man show that, in the absence of unilateral disease, the supine renal venous renin level in each kidney is consistently 24 percent higher than the peripheral level. Because of this constant relationship, the peripheral renin level is a measure of the renal secretion rate. Our studies indicate the curable unilateral renovascular hypertension is, in fact, renin-dependent vasoconstrictor hypertension. Three criteria, derived from four renin measurements, identify this situation: (1) Hypersecretion of renin is reflected by a high peripheral level when indexed against sodium excretion. (2) Lateralization of renin secretion with contralateral suppression rules out occult bilateral disease. It is indicated by V-A equal 0 from the uninvolved kidney. (3) (V-A)/A greater than 48 per cent from the ipsilateral kidney  supports unilateralization. With data derived from patients with essential hypertension as a reference, the degree to which (V-A)/A is greater than 0.48 can be used to estimate the degree of renal ischemia, using Fick's principle. Corroborative evidence to support these three criteria can be developed from the blood pressure response to angiotensin blocking drugs or to antirenin therapy with propranolol. Clinical analysis validates these criteria to identify curable hypertension from unilateral renovascular or parenchymal disease. In patients with either occult or overt bilateral renal disease, the volume factor often predominates and is expressed by some suppression of plasma renin levels. Continued", "contents": "The renin axis and vasoconstriction volume analysis for understanding and treating renovascular and renal hypertension. Information defining the renin-angiotension-aldosterone axis as a control system concurrently regulating salt balance and blood pressure has been applied to reexamine the role of renin in experimental and clinical forms of renovascular and renal hypertension, and thence to develop criteria for differentiating these entities. Experimentally, there are two models of renovascular hypertension; one is characterized by excess renin with reduced sodium (vasoconstrictor form) and the other by excess sodium with reduced renin (volume form). But with sodium depletion, the volume form converts to a vasoconstrictor form illustrating how the two factors coordinate to maintain blood pressure. In man, renovascular and renal hypertensions appear to be sustained by the same two mechanisms. Studies in man show that, in the absence of unilateral disease, the supine renal venous renin level in each kidney is consistently 24 percent higher than the peripheral level. Because of this constant relationship, the peripheral renin level is a measure of the renal secretion rate. Our studies indicate the curable unilateral renovascular hypertension is, in fact, renin-dependent vasoconstrictor hypertension. Three criteria, derived from four renin measurements, identify this situation: (1) Hypersecretion of renin is reflected by a high peripheral level when indexed against sodium excretion. (2) Lateralization of renin secretion with contralateral suppression rules out occult bilateral disease. It is indicated by V-A equal 0 from the uninvolved kidney. (3) (V-A)/A greater than 48 per cent from the ipsilateral kidney  supports unilateralization. With data derived from patients with essential hypertension as a reference, the degree to which (V-A)/A is greater than 0.48 can be used to estimate the degree of renal ischemia, using Fick's principle. Corroborative evidence to support these three criteria can be developed from the blood pressure response to angiotensin blocking drugs or to antirenin therapy with propranolol. Clinical analysis validates these criteria to identify curable hypertension from unilateral renovascular or parenchymal disease. In patients with either occult or overt bilateral renal disease, the volume factor often predominates and is expressed by some suppression of plasma renin levels. Continued"}
{"id": "PMID:234678", "title": "Role of anaerobic bacteria in subdural empyema. Report of four cases and review of 327 cases from the English literature.", "content": "Anaerobic bacteria were isolated from the subdural space in all four cases of subdural empyema encountered over a 2 and a half year period. Only one aerobe was isolated in these cases. The bacteriology of subdural empyema was further analyzed from a review of 327 cases reported in the English literature. Anaerobes accounted for 12 per cent of 234 cases; In addition, 27 per cent of cases were reportedly \"sterile.\" These data support our finding that anaerobic bacteria may play a far more important role in subdural empyema than was previously appreciated.", "contents": "Role of anaerobic bacteria in subdural empyema. Report of four cases and review of 327 cases from the English literature. Anaerobic bacteria were isolated from the subdural space in all four cases of subdural empyema encountered over a 2 and a half year period. Only one aerobe was isolated in these cases. The bacteriology of subdural empyema was further analyzed from a review of 327 cases reported in the English literature. Anaerobes accounted for 12 per cent of 234 cases; In addition, 27 per cent of cases were reportedly \"sterile.\" These data support our finding that anaerobic bacteria may play a far more important role in subdural empyema than was previously appreciated."}
{"id": "PMID:234679", "title": "Gram-negative bacillary endocarditis. Interpretation of the serum bactericial test.", "content": "Although the serum bactericidal test is commonly used in the management of infective endocarditis, little has been written about its validity or limitations. We report three cases of gram-negative bacillary endocarditis (Pseudomonas aeruginosa, Vibrio fetus and Serratia marcescens) encountered in 1 year at a Veterans Administration hospital. Serum bactericidal titers were considered necessary to identify inadequate antibiotic regimens or to avoid unnecessary drug toxicity. The limitations of the test, particularly those pertaining to gram-negative infections, are reviewed. Misleading results during treatment with aminoglycoside antibiotics could be due to the tendency of serum to become alkaline on standing. A detailed study of the interaction of the complement-dependent bactericidal system of serum with eight antibiotics is presented. In the context of the serum bactericidal test, the interaction was additive or synergistic in 15 of 16 determinations, indicating the need to include a control study of serum sensitivity of the infecting microorganism in each case.", "contents": "Gram-negative bacillary endocarditis. Interpretation of the serum bactericial test. Although the serum bactericidal test is commonly used in the management of infective endocarditis, little has been written about its validity or limitations. We report three cases of gram-negative bacillary endocarditis (Pseudomonas aeruginosa, Vibrio fetus and Serratia marcescens) encountered in 1 year at a Veterans Administration hospital. Serum bactericidal titers were considered necessary to identify inadequate antibiotic regimens or to avoid unnecessary drug toxicity. The limitations of the test, particularly those pertaining to gram-negative infections, are reviewed. Misleading results during treatment with aminoglycoside antibiotics could be due to the tendency of serum to become alkaline on standing. A detailed study of the interaction of the complement-dependent bactericidal system of serum with eight antibiotics is presented. In the context of the serum bactericidal test, the interaction was additive or synergistic in 15 of 16 determinations, indicating the need to include a control study of serum sensitivity of the infecting microorganism in each case."}
{"id": "PMID:234680", "title": "Current concepts on physiological control of gastric acid secretion. Clinical applications.", "content": "Gastric acid secretion by the parietal cell is a single digestive process involving a continuous interplay between nervous and hormonal stimuli. Gastric acid hypersecretion and hypergastrinemia may represent pathologic disturbance of the normal \"gastric phase\" of acid secretion (excluded antrum syndrome) or abnormal gastrin secretion from a nongastric source as in the Zollinger-Ellison syndrome. Diagnosis of these two syndromes preoperatively is dependent on immunoassay for serum gastrin. A fall in serum gastrin level after the injection of secretin will distinguish the excluded antrum syndrome from the Zollinger-Ellison syndrome. Which hormone or hormones cause the acid hyposecretion of the watery diarrhea hypokalemia achlorhydria syndrome is still uncertain. Potential candidates include secretin, glucagon (alone or combined with gastrin), vasoactive intestinal peptide and gastric inhibitory polypeptide. Secretin has undergone trials as therapy in peptic ulcer whereas glucagon is under investigation for the treatment of acute pancreatitis because of its dual actions as (1) an enterogastrone and (2) an inhibitor of pancreatic secretion.", "contents": "Current concepts on physiological control of gastric acid secretion. Clinical applications. Gastric acid secretion by the parietal cell is a single digestive process involving a continuous interplay between nervous and hormonal stimuli. Gastric acid hypersecretion and hypergastrinemia may represent pathologic disturbance of the normal \"gastric phase\" of acid secretion (excluded antrum syndrome) or abnormal gastrin secretion from a nongastric source as in the Zollinger-Ellison syndrome. Diagnosis of these two syndromes preoperatively is dependent on immunoassay for serum gastrin. A fall in serum gastrin level after the injection of secretin will distinguish the excluded antrum syndrome from the Zollinger-Ellison syndrome. Which hormone or hormones cause the acid hyposecretion of the watery diarrhea hypokalemia achlorhydria syndrome is still uncertain. Potential candidates include secretin, glucagon (alone or combined with gastrin), vasoactive intestinal peptide and gastric inhibitory polypeptide. Secretin has undergone trials as therapy in peptic ulcer whereas glucagon is under investigation for the treatment of acute pancreatitis because of its dual actions as (1) an enterogastrone and (2) an inhibitor of pancreatic secretion."}
{"id": "PMID:234682", "title": "Enzymes of glucose and fatty acid metabolism in early and term human placenta.", "content": "The activity of enzymes involved in glycolysis, gluconeogenesis, and lipoenesis in early and term human placenta was determined. A high activity of pyruvate kinase was found, indicating high glycolytic potential. The activity of this enzyme tended to decrease with gestation. The presence of phosphoenolpyruvate carboxylase activity was detected, suggesting the possibility of gluconeogenesis in the placenta. Very low activity of enzymes involved in fatty acid synthesis was found, whereas the activity of the pentose shunt pathway enzymes, glucose-6-phosphogluconate dehydrogenases, was relatively high. This suggested a role of this pathway in the synthesis of lipids other than fatty acids in the placenta. The activities of enzymes in the human placenta and their changes during gestation where compared to previous observations on enzymes in rat placenta.", "contents": "Enzymes of glucose and fatty acid metabolism in early and term human placenta. The activity of enzymes involved in glycolysis, gluconeogenesis, and lipoenesis in early and term human placenta was determined. A high activity of pyruvate kinase was found, indicating high glycolytic potential. The activity of this enzyme tended to decrease with gestation. The presence of phosphoenolpyruvate carboxylase activity was detected, suggesting the possibility of gluconeogenesis in the placenta. Very low activity of enzymes involved in fatty acid synthesis was found, whereas the activity of the pentose shunt pathway enzymes, glucose-6-phosphogluconate dehydrogenases, was relatively high. This suggested a role of this pathway in the synthesis of lipids other than fatty acids in the placenta. The activities of enzymes in the human placenta and their changes during gestation where compared to previous observations on enzymes in rat placenta."}
{"id": "PMID:234684", "title": "Lumbar epidural analgesia with bupivacaine in labor. Determination of drug concentration and pH in fetal scalp blood, and continuous fetal heart rate monitoring.", "content": "Lumbar epiduval analgesia with bupivacaine was given to 37 women for uncomplicated labor. After the blcokade serial determinations of pH and bupivacaine concentration were made in fetal scalp blood and maternal venous blood and there was continuous monitoring of the fetal heart rate. Fetal scalp blood pH was within normal limits and no pathologic FHR tracings were elicited by the blockade, although a temporary decrease of the baseline fetal heart rate irregularity was seen in about one-fifth of the cases. Fetal drug concentrations were low and about one-fourth of corresponding maternal values. After reinjection of bupivacaine the degree of drug accumulation was fairly similar in fetal and maternal blood.", "contents": "Lumbar epidural analgesia with bupivacaine in labor. Determination of drug concentration and pH in fetal scalp blood, and continuous fetal heart rate monitoring. Lumbar epiduval analgesia with bupivacaine was given to 37 women for uncomplicated labor. After the blcokade serial determinations of pH and bupivacaine concentration were made in fetal scalp blood and maternal venous blood and there was continuous monitoring of the fetal heart rate. Fetal scalp blood pH was within normal limits and no pathologic FHR tracings were elicited by the blockade, although a temporary decrease of the baseline fetal heart rate irregularity was seen in about one-fifth of the cases. Fetal drug concentrations were low and about one-fourth of corresponding maternal values. After reinjection of bupivacaine the degree of drug accumulation was fairly similar in fetal and maternal blood."}
{"id": "PMID:234685", "title": "The effect of berotec (Th 1165a) on spontaneous and induced uterine activity in the pregnant baboon.", "content": "Berotec (Th 1165a), a specific beta-adrenergic agent, has been found to be a more potent agent than metaproterenol in the inhibition of uterine activity in animals and human beings. The effect of berotec on spontaneous (postinduced) and induced uterine activity in the pregnant baboon near term was investigated. Berotec administered intravenously in a dose of 5 mug per minute consistently and significantly reduced spontaneous uterine activity as well as uterine activity by either oxytocin or prostaglandin F2-alpha. The frequency of contractions was consistently reduced whereas the effect on the amplitude of contractions was less marked. There was no reduction of the baseline muscle tonus. Berotec infusion produced a marked increase in the maternal heart rate, averaging 40 beats per minute. Berotec appears to be a potent inhibitor of spontaneous, oxytocin-induced, and prostaglandin-induced uterine activity in the pregnant baboon, but it has considerable cardiovascular side effects.", "contents": "The effect of berotec (Th 1165a) on spontaneous and induced uterine activity in the pregnant baboon. Berotec (Th 1165a), a specific beta-adrenergic agent, has been found to be a more potent agent than metaproterenol in the inhibition of uterine activity in animals and human beings. The effect of berotec on spontaneous (postinduced) and induced uterine activity in the pregnant baboon near term was investigated. Berotec administered intravenously in a dose of 5 mug per minute consistently and significantly reduced spontaneous uterine activity as well as uterine activity by either oxytocin or prostaglandin F2-alpha. The frequency of contractions was consistently reduced whereas the effect on the amplitude of contractions was less marked. There was no reduction of the baseline muscle tonus. Berotec infusion produced a marked increase in the maternal heart rate, averaging 40 beats per minute. Berotec appears to be a potent inhibitor of spontaneous, oxytocin-induced, and prostaglandin-induced uterine activity in the pregnant baboon, but it has considerable cardiovascular side effects."}
{"id": "PMID:234687", "title": "Delay in seeking induced abortion: a review and theoretical analysis.", "content": "Second-trimester abortion is known to be associated with increased morbidity and mortality rates. In this paper, possible reasons for delayed abortion are examined by: (1) reviewing the available literature to seek a synthesis of current findings, (2) discussing the findings within the theoretical context of decision-making under conflict which offers a conceptual framework for further understanding delay in seeking abortion, and (3) pointing to some methodologic problems in studies of delay in seeking abortion.", "contents": "Delay in seeking induced abortion: a review and theoretical analysis. Second-trimester abortion is known to be associated with increased morbidity and mortality rates. In this paper, possible reasons for delayed abortion are examined by: (1) reviewing the available literature to seek a synthesis of current findings, (2) discussing the findings within the theoretical context of decision-making under conflict which offers a conceptual framework for further understanding delay in seeking abortion, and (3) pointing to some methodologic problems in studies of delay in seeking abortion."}
{"id": "PMID:234688", "title": "Effect of osmolarity on intracellular pH of rat diaphragm muscle.?22.", "content": "To investigate the effect of altered extracellular osmolarity on cell pH, intact rat diaphragms were incubated in a Krebs-Ringer bicarbonate solution. Cell pH was measured simultaneously by weak-acid (pH DMO) or weak-base (ph nicotine) distribution. When osmolarity was raised by mannitol addition, cell water decreased 5-10% (P smaller than .01) while both pH DMO and pH nicotine increased (P smaller than .01) under acid, normal, and alkaline external pH conditions. Hyperosmolarity of identical degree caused by urea resulted in no changes in either cell water or cell pH. Identical amounts of mannitol added to the bath in the absence of external osmolar changes resulted in no changes in either cell water or cell pH. When extracellular osmolarity was lowered by decreasing sodium chloride concentration, cell water increased 10-12% (P smaller than .01). Despite this large change in cell water, no changes in pH DMO or pH nicotine occurred. These data indicate that osmolar induced alterations in cell water only partially explain cell pH changes found in abnormal osmolar states. Alterations in passive and active hydrogen ion transport must also play significant roles.", "contents": "Effect of osmolarity on intracellular pH of rat diaphragm muscle.?22. To investigate the effect of altered extracellular osmolarity on cell pH, intact rat diaphragms were incubated in a Krebs-Ringer bicarbonate solution. Cell pH was measured simultaneously by weak-acid (pH DMO) or weak-base (ph nicotine) distribution. When osmolarity was raised by mannitol addition, cell water decreased 5-10% (P smaller than .01) while both pH DMO and pH nicotine increased (P smaller than .01) under acid, normal, and alkaline external pH conditions. Hyperosmolarity of identical degree caused by urea resulted in no changes in either cell water or cell pH. Identical amounts of mannitol added to the bath in the absence of external osmolar changes resulted in no changes in either cell water or cell pH. When extracellular osmolarity was lowered by decreasing sodium chloride concentration, cell water increased 10-12% (P smaller than .01). Despite this large change in cell water, no changes in pH DMO or pH nicotine occurred. These data indicate that osmolar induced alterations in cell water only partially explain cell pH changes found in abnormal osmolar states. Alterations in passive and active hydrogen ion transport must also play significant roles."}
{"id": "PMID:234689", "title": "Fate of labeled angiotensin II microinfused into individual nephrons in the rat.", "content": "14C-labeled angiotensin II ([14C]AII) and tritiated inulin ([3H]In) were infused into individual nephrons in Inactin-anesthetized rats and urinary excretion was measured. Site of infusion was identified by neoprene injection and microdissection. In other experiments with higher doses of [14C]AII, microperfused at 10-4-10-5 M (concentrations 10-5-10-6 higher than contained in plasma), [14C]AII and its urinary metabolites were identified and quantified by two-dimensional peptide mapping. Recovery of 14C was 10.9% when proximal tubules were infused and 94.8% when distal tubules were infused. There was no correlation with tubular length in either case. For proximal tubules, two-thirds of the 11% recovered from urine appeared as peptide fragments of AII. With distal tubules almost all 14C activity appeared as intact AII. The principal metabolic product recovered from urine after proximal injection was the chymotryptic peptide, and its recovery was inversely related to tubular length. It is suggested that rapid removal of [14C]AII by proximal tubular cells occurs by enzymatic cleavage at the luminal surface with reabsorption of most of the products and excretion of the remainder", "contents": "Fate of labeled angiotensin II microinfused into individual nephrons in the rat. 14C-labeled angiotensin II ([14C]AII) and tritiated inulin ([3H]In) were infused into individual nephrons in Inactin-anesthetized rats and urinary excretion was measured. Site of infusion was identified by neoprene injection and microdissection. In other experiments with higher doses of [14C]AII, microperfused at 10-4-10-5 M (concentrations 10-5-10-6 higher than contained in plasma), [14C]AII and its urinary metabolites were identified and quantified by two-dimensional peptide mapping. Recovery of 14C was 10.9% when proximal tubules were infused and 94.8% when distal tubules were infused. There was no correlation with tubular length in either case. For proximal tubules, two-thirds of the 11% recovered from urine appeared as peptide fragments of AII. With distal tubules almost all 14C activity appeared as intact AII. The principal metabolic product recovered from urine after proximal injection was the chymotryptic peptide, and its recovery was inversely related to tubular length. It is suggested that rapid removal of [14C]AII by proximal tubular cells occurs by enzymatic cleavage at the luminal surface with reabsorption of most of the products and excretion of the remainder"}
{"id": "PMID:234690", "title": "Lung vascular smooth muscle as a determinant of pulmonary hypertension at high altitude.", "content": "The pulmonary hypertensive response to chronic hypoxia varies markedly among mammalian species. An explanation for this variability was sought by exposing seven species to hypobaric hypoxia (PB equal to 435 mmHg) for 19-48 days. Control animals were studied at 1,600 m (PB equal to 630 mmHg). The pulmonary hypertension that developed varied in the following order of decreasing severity: calf and pig (severe); rat and rabbit (moderate); sheep, guinea pig, and dog (mild). Right ventricular hypertrophy developed in proportion to the elevation in right ventricular systolic pressure. These interspecies variations in response were not correlated with the degree of arterial hypoxemia, degree of polycythemia, elevation in heart rate, or postnatal age. However, the medial thickness of the small pulmonary arteries in control animals was highly correlated with the development of pulmonary hypertension and right ventricular hypertrophy in hypoxic animals. Thus, the amount of lung vascular smooth muscle inherent within each species is a major determinant of the pulmonary hypertensive response to high altitude and contributes to the interspecies variability in this response.", "contents": "Lung vascular smooth muscle as a determinant of pulmonary hypertension at high altitude. The pulmonary hypertensive response to chronic hypoxia varies markedly among mammalian species. An explanation for this variability was sought by exposing seven species to hypobaric hypoxia (PB equal to 435 mmHg) for 19-48 days. Control animals were studied at 1,600 m (PB equal to 630 mmHg). The pulmonary hypertension that developed varied in the following order of decreasing severity: calf and pig (severe); rat and rabbit (moderate); sheep, guinea pig, and dog (mild). Right ventricular hypertrophy developed in proportion to the elevation in right ventricular systolic pressure. These interspecies variations in response were not correlated with the degree of arterial hypoxemia, degree of polycythemia, elevation in heart rate, or postnatal age. However, the medial thickness of the small pulmonary arteries in control animals was highly correlated with the development of pulmonary hypertension and right ventricular hypertrophy in hypoxic animals. Thus, the amount of lung vascular smooth muscle inherent within each species is a major determinant of the pulmonary hypertensive response to high altitude and contributes to the interspecies variability in this response."}
{"id": "PMID:234691", "title": "ATPase activity of kidney mitochondria stimulated by sodium.", "content": "ATPase activity of intact mitochondria may be induced by the presence of sodium. Mitochondria obtained from kidney cortex or medulla demonstrate a higher sodium-stimulated ATPase than mitochondria prepared from liver. This difference is not due to a greater capacity of kidney mitochondria for ATP hydrolysis. Sodium-stimulated ATPase activity of mitochondria is not further enhanced by magnesium or potassium, nor is it inhibited by ouabain. Furthermore, the ATPase of submitochondrial particles is not enhanced by the presence of sodium. These results indicate that the ATPase activity of mitochondria which is stimulated by sodium is unrelated to the microsomal Na-K-ATPase. mitochondrial sodium-stimulated ATPase is affected by pH, anionic composition, furosemide, and ethacrynic acid. The demonstration that mitochondrial ATP hydrolysis can be activated by sodium suggests that intracellular sodium may directly influence intracellular energy metabolism.", "contents": "ATPase activity of kidney mitochondria stimulated by sodium. ATPase activity of intact mitochondria may be induced by the presence of sodium. Mitochondria obtained from kidney cortex or medulla demonstrate a higher sodium-stimulated ATPase than mitochondria prepared from liver. This difference is not due to a greater capacity of kidney mitochondria for ATP hydrolysis. Sodium-stimulated ATPase activity of mitochondria is not further enhanced by magnesium or potassium, nor is it inhibited by ouabain. Furthermore, the ATPase of submitochondrial particles is not enhanced by the presence of sodium. These results indicate that the ATPase activity of mitochondria which is stimulated by sodium is unrelated to the microsomal Na-K-ATPase. mitochondrial sodium-stimulated ATPase is affected by pH, anionic composition, furosemide, and ethacrynic acid. The demonstration that mitochondrial ATP hydrolysis can be activated by sodium suggests that intracellular sodium may directly influence intracellular energy metabolism."}
{"id": "PMID:234692", "title": "In vivo Na+- and Cl minus-independent transport across the skin of Rana esculenta.", "content": "The relationship between the trans-epithelial Na+ and Cl minus absorptions from dilute external solutions and the H+ and base excretions were studied in Rana esculenta in vivo. The following results relate to transport from Na2SO4 solutions: 1) The Na+ absorbed is exchanged against endogenous H+. 2) Diamox injection (1.10-4 M-kg-1) simultaneously inhibits both Na+ absorption and H+ excretion. 3) The addition of amiloride to the external medium (final concn: 5-10-5 M) inhibits Na+ absorption and H+ excretion. Measurements of chloride movements from choline chloride solutions give the following results: 1) The chloride absorbed is exchanged against a base, probably HCO3-. 2) Diamox injection (1-10-4 M-kg-1)inhibits the net fluxes of both ions. When transport is measured in NaCl solutions, it is impossible to measure the HCO3-excreted when H+ is also being excreted (HCO3- plus H+ in equilibrium CO2 plus H2O). In these solutions, therefore, only the action of Diamox on the sodium and chloride fluxes was followed and was found to have similar effects on these fluxes as those described for choline chloride and sodium sulphate solutions. The results are discussed in relation to other studies on the action of inhibitors on sodium and chloride transport in the in vitro skin.", "contents": "In vivo Na+- and Cl minus-independent transport across the skin of Rana esculenta. The relationship between the trans-epithelial Na+ and Cl minus absorptions from dilute external solutions and the H+ and base excretions were studied in Rana esculenta in vivo. The following results relate to transport from Na2SO4 solutions: 1) The Na+ absorbed is exchanged against endogenous H+. 2) Diamox injection (1.10-4 M-kg-1) simultaneously inhibits both Na+ absorption and H+ excretion. 3) The addition of amiloride to the external medium (final concn: 5-10-5 M) inhibits Na+ absorption and H+ excretion. Measurements of chloride movements from choline chloride solutions give the following results: 1) The chloride absorbed is exchanged against a base, probably HCO3-. 2) Diamox injection (1-10-4 M-kg-1)inhibits the net fluxes of both ions. When transport is measured in NaCl solutions, it is impossible to measure the HCO3-excreted when H+ is also being excreted (HCO3- plus H+ in equilibrium CO2 plus H2O). In these solutions, therefore, only the action of Diamox on the sodium and chloride fluxes was followed and was found to have similar effects on these fluxes as those described for choline chloride and sodium sulphate solutions. The results are discussed in relation to other studies on the action of inhibitors on sodium and chloride transport in the in vitro skin."}
{"id": "PMID:234693", "title": "Effect of infusion of pharmacologic amounts of vasopressin on renal electrolyte excretion.", "content": "Aqueous vasopressin was infused to bicarbonate- and glucose-loaded dogs and to nonloaded antidiuretic dogs in doses of 50 mU/kg per min or 50 mU/kg per h. Both doses caused a marked increase in sodium, chloride, and water excretion. The larger dose raised the fractional excretion (sodium clearance (C-Na)/glomerular filtration rate (GFR) times 100) of these ions from 2% or less to in excess of 20%. Blocking the pressor effects of these doses of vasopressin with sodium nitroprusside did not alter the marked natriuretic and chloriuretic effect.  The maximal rate of bicarbonate and glucose reabsorption was not depressed by vasopressin infusion; fractional phosphate excretion, however, was markedly increased. Inhibiting distal hydrogen ion secretion by inducing selective aldosterone deficiency failed to uncover a vasopressin-induced inhibition of proximal bicarbonate reabsorption that might have been masked by increased distal bicarbonate reabsorption. There was no significant change in GFR, renal plasma flow, or filtration fraction. The distribution of cortical renal blood flow (measured by the radioactive microsphere technique) shifted toward the inner cortex after vasopressin administration. Vasopressin, in pharmacologic doses, is a potent diuretic that most likely exerts this effect by directly inhibiting sodium reabsorption at a point in the nephron distal to the proximal tubule.", "contents": "Effect of infusion of pharmacologic amounts of vasopressin on renal electrolyte excretion. Aqueous vasopressin was infused to bicarbonate- and glucose-loaded dogs and to nonloaded antidiuretic dogs in doses of 50 mU/kg per min or 50 mU/kg per h. Both doses caused a marked increase in sodium, chloride, and water excretion. The larger dose raised the fractional excretion (sodium clearance (C-Na)/glomerular filtration rate (GFR) times 100) of these ions from 2% or less to in excess of 20%. Blocking the pressor effects of these doses of vasopressin with sodium nitroprusside did not alter the marked natriuretic and chloriuretic effect.  The maximal rate of bicarbonate and glucose reabsorption was not depressed by vasopressin infusion; fractional phosphate excretion, however, was markedly increased. Inhibiting distal hydrogen ion secretion by inducing selective aldosterone deficiency failed to uncover a vasopressin-induced inhibition of proximal bicarbonate reabsorption that might have been masked by increased distal bicarbonate reabsorption. There was no significant change in GFR, renal plasma flow, or filtration fraction. The distribution of cortical renal blood flow (measured by the radioactive microsphere technique) shifted toward the inner cortex after vasopressin administration. Vasopressin, in pharmacologic doses, is a potent diuretic that most likely exerts this effect by directly inhibiting sodium reabsorption at a point in the nephron distal to the proximal tubule."}
{"id": "PMID:234694", "title": "Electrophysiology of the frog gastric mucosa with sufficient CO2.", "content": "Changing from 5% CO2 in the serosal solution only to 10% CO2 on both sides doubles the acid secretory rate of the bullfrog stomach (as shown previously) and raises the transmural potential difference, although the short-circuit current is not changed. The secretory overshoot on reoxygenation after anaerobiosis, observed in 5% CO2, is virtually eliminated in 10% CO2, as predicted by the diffusion model which explains the secretory rate increase. It was found that the rate of rise of the secretory rate during anoxia was identical in the 2 conditions, which explains the increased secretory lag in 10% CO2 and suggests an interesting limitation on the rate with which acid secretion can be activated. During anoxia in 10% CO2, but not in 5% CO2, there occurs a sudden drop in PD to a slightly negative value associated with a fall in tissue resistance. This effect occurs under SCN-inhibition and thus seems unrelated to H+ transport per se. A working model is presented which can explain some of the events surrounding the sudden potential drop.", "contents": "Electrophysiology of the frog gastric mucosa with sufficient CO2. Changing from 5% CO2 in the serosal solution only to 10% CO2 on both sides doubles the acid secretory rate of the bullfrog stomach (as shown previously) and raises the transmural potential difference, although the short-circuit current is not changed. The secretory overshoot on reoxygenation after anaerobiosis, observed in 5% CO2, is virtually eliminated in 10% CO2, as predicted by the diffusion model which explains the secretory rate increase. It was found that the rate of rise of the secretory rate during anoxia was identical in the 2 conditions, which explains the increased secretory lag in 10% CO2 and suggests an interesting limitation on the rate with which acid secretion can be activated. During anoxia in 10% CO2, but not in 5% CO2, there occurs a sudden drop in PD to a slightly negative value associated with a fall in tissue resistance. This effect occurs under SCN-inhibition and thus seems unrelated to H+ transport per se. A working model is presented which can explain some of the events surrounding the sudden potential drop."}
{"id": "PMID:234695", "title": "Characteristics of in vitro ammonia and glucose production by dog kidney cortex.", "content": "Renal cortex slices from acidotic dogs incubated with L-glutamine 1 mM at pH 7.05 produced more ammonia and glucose than slices from nonacidotic animals but no significant difference could be demonstrated at pH 7.48. At a phosphate concentration of 20-30 mM in the medium, a 20-30% increase in ammonia and a 25-40% decrease in glucose production were observed. At L-glutamine concentrations from 0 to 8 mM, a curvilinear increase in both ammonia and glucose production was noted, the effect being greater in slices from acidotic animals. D-Glutamine had little effect on ammoniagenesis. Ammonia production (1 mM L-glutamine) in vitro was 50% lower in acidotic dogs than in vivo. Slices from the remnant left kidney (4-6 wk after right nephrectomy) did not behave differently during acidosis than those from the right kidney with regard to ammonia or glucose production. In vitro ammonia and glucose production was higher in the rat than in the dog in acidotic and nonacidotic conditions when comparable concentrations of L-glutamine substrate were used.", "contents": "Characteristics of in vitro ammonia and glucose production by dog kidney cortex. Renal cortex slices from acidotic dogs incubated with L-glutamine 1 mM at pH 7.05 produced more ammonia and glucose than slices from nonacidotic animals but no significant difference could be demonstrated at pH 7.48. At a phosphate concentration of 20-30 mM in the medium, a 20-30% increase in ammonia and a 25-40% decrease in glucose production were observed. At L-glutamine concentrations from 0 to 8 mM, a curvilinear increase in both ammonia and glucose production was noted, the effect being greater in slices from acidotic animals. D-Glutamine had little effect on ammoniagenesis. Ammonia production (1 mM L-glutamine) in vitro was 50% lower in acidotic dogs than in vivo. Slices from the remnant left kidney (4-6 wk after right nephrectomy) did not behave differently during acidosis than those from the right kidney with regard to ammonia or glucose production. In vitro ammonia and glucose production was higher in the rat than in the dog in acidotic and nonacidotic conditions when comparable concentrations of L-glutamine substrate were used."}
{"id": "PMID:234696", "title": "Personality and behavior patterns of heroin-dependent American servicemen in Thailand.", "content": "The authors compared a groups of heroin-dependent American servicemen stationed in Thailand with a matched control groups of men not dependent on heroin. The data gathered regarding social history, attitudes, work record, previous drug use, personality, and intelligence show significant differences between the heroin-dependent men and the control group in four areas: intelligence, work record, number of years of schooling and number of drug used before using heroin. The data suggest that many of the heroin-dependent men had difficulties related to a distant or negative relationship to their fathers; however, in contrast to previous studies of heroin addicts, they do not confirm a relationship between heroin dependence and any particular personality pattern.", "contents": "Personality and behavior patterns of heroin-dependent American servicemen in Thailand. The authors compared a groups of heroin-dependent American servicemen stationed in Thailand with a matched control groups of men not dependent on heroin. The data gathered regarding social history, attitudes, work record, previous drug use, personality, and intelligence show significant differences between the heroin-dependent men and the control group in four areas: intelligence, work record, number of years of schooling and number of drug used before using heroin. The data suggest that many of the heroin-dependent men had difficulties related to a distant or negative relationship to their fathers; however, in contrast to previous studies of heroin addicts, they do not confirm a relationship between heroin dependence and any particular personality pattern."}
{"id": "PMID:234701", "title": "Renal clearance and excretion of endogenous substances in the small pony.", "content": "Renal clearance and excretion of endogenous substances were studied in 13 small adult ponies (152 plus or minus 93 (standard deviation (SD)) kg). Normal data of serum and urinary concentrations, clearance, and excretion of creatinine, osmolality, free water, sodium, potassium, and chloride during a 12-hour period are presented. Significant linear regressions on body weight (BW) were obtained for creatinine clearance (Ccr (ml/hr) = 127.2 times BW (kg) - 1553), osmolar clearance (Cosm(ml/hr) = 1.81 times BW (kg) m0.3), and free water (CH2O(ml/hr) = - 1.43 BW (kg) - 25.0). Compared with renal excretion of man, kidneys of ponies seem to conserve more sodium and chloride and excrete more potassium.", "contents": "Renal clearance and excretion of endogenous substances in the small pony. Renal clearance and excretion of endogenous substances were studied in 13 small adult ponies (152 plus or minus 93 (standard deviation (SD)) kg). Normal data of serum and urinary concentrations, clearance, and excretion of creatinine, osmolality, free water, sodium, potassium, and chloride during a 12-hour period are presented. Significant linear regressions on body weight (BW) were obtained for creatinine clearance (Ccr (ml/hr) = 127.2 times BW (kg) - 1553), osmolar clearance (Cosm(ml/hr) = 1.81 times BW (kg) m0.3), and free water (CH2O(ml/hr) = - 1.43 BW (kg) - 25.0). Compared with renal excretion of man, kidneys of ponies seem to conserve more sodium and chloride and excrete more potassium."}
{"id": "PMID:234702", "title": "Hypoxic pulmonary hypertension in the pony.", "content": "Hemodynamic measurements were made in 6 ponies at low altitude (Madison, WI, altitude, 250 m) and after 1, 2, 4, and 6 weeks at high altitude (Climax, CO, altitude, 3,400 m). The salient findings were that ponies maintain an increased heart rate and cardiac output and develop significant pulmonary hypertension at high altitude. The average control resting mean pulmonary artery pressure (BPpul) was 25.1 mm of Hg at 250 m; this value increased to 56.3 mm of Hg after 6 weeks at 3,400 m. An additional finding was that the pulmonary vascular response to acute hypoxia seemed to increase with time at high altitude.", "contents": "Hypoxic pulmonary hypertension in the pony. Hemodynamic measurements were made in 6 ponies at low altitude (Madison, WI, altitude, 250 m) and after 1, 2, 4, and 6 weeks at high altitude (Climax, CO, altitude, 3,400 m). The salient findings were that ponies maintain an increased heart rate and cardiac output and develop significant pulmonary hypertension at high altitude. The average control resting mean pulmonary artery pressure (BPpul) was 25.1 mm of Hg at 250 m; this value increased to 56.3 mm of Hg after 6 weeks at 3,400 m. An additional finding was that the pulmonary vascular response to acute hypoxia seemed to increase with time at high altitude."}
{"id": "PMID:234699", "title": "Intermittent mandatory ventilation: an alternative weaning technic. A case report.", "content": "Many variations of measurement have been proposed for determining when a patient may be weaned from artificial ventilation. The present case report describes successful use of intermittent mandatory ventilation for weaning a patient when measurements had indicated weaning would not be possible.", "contents": "Intermittent mandatory ventilation: an alternative weaning technic. A case report. Many variations of measurement have been proposed for determining when a patient may be weaned from artificial ventilation. The present case report describes successful use of intermittent mandatory ventilation for weaning a patient when measurements had indicated weaning would not be possible."}
{"id": "PMID:234703", "title": "Immunity to leptospirosis: antiserums in dogs and hamsters.", "content": "Resistance to clinical and renal leptospirosis in dogs injected with antiserum to Leptospira interrogans serotype canicola and Leptospira interrogans serotype icterohaemorrhagiae was demonstrated. The relationship between resistance induced in serum-injected hamsters was also demonstrated, using criteria of leptospiremia, renal infection, leptospiruria, and clinical signs of disease in dogs and death in hamsters.", "contents": "Immunity to leptospirosis: antiserums in dogs and hamsters. Resistance to clinical and renal leptospirosis in dogs injected with antiserum to Leptospira interrogans serotype canicola and Leptospira interrogans serotype icterohaemorrhagiae was demonstrated. The relationship between resistance induced in serum-injected hamsters was also demonstrated, using criteria of leptospiremia, renal infection, leptospiruria, and clinical signs of disease in dogs and death in hamsters."}
{"id": "PMID:234704", "title": "Immunity to leptospirosis: bacterins in dogs and hamsters.", "content": "Resistance to clinical and renal leptospirosis in dogs vaccinated with a bacterin containing Leptospira interrogans serotype canicola and Leptospira interrogans serotype icterohaemorrhagiae was demonstrated. The relationship between resistance induced in vaccinated dogs and that induced in vaccinated hamsters was also demonstrated, using criteria of leptospiremia, renal infection, leptospiruria, and clinical signs of disease in dogs and death in hamsters.", "contents": "Immunity to leptospirosis: bacterins in dogs and hamsters. Resistance to clinical and renal leptospirosis in dogs vaccinated with a bacterin containing Leptospira interrogans serotype canicola and Leptospira interrogans serotype icterohaemorrhagiae was demonstrated. The relationship between resistance induced in vaccinated dogs and that induced in vaccinated hamsters was also demonstrated, using criteria of leptospiremia, renal infection, leptospiruria, and clinical signs of disease in dogs and death in hamsters."}
{"id": "PMID:234700", "title": "The influence of chronic administration of hypnotics and analgesics on rate of recovery from inhalation anesthesia in rats.", "content": "A series of groups of Sprague-Dawley rats were given either secobarbital, phenobarbital, morphine, pentazocine, diazepam, methotrimeprazine, or saline (control) intraperitoneally on 4 consecutive days and then, on day 5, anesthetized with chloroform, trichlorethylene, fluroxene, halothane, methoxyflurane, enflurane, isoflurane, bromotrifluorocyclobutane, or chlorotrifluorocyclobutane. One control group received neither pretreatment nor anesthetics and another was given pretreatment but no anesthetics. The factor of \"enzyme induction\" is also evaluated, as are SGPT elevation and liver and kidney lesions. If enzyme induction occurred with the drugs used for pretreatment, the anesthetics suppressed the expected response. SGPT levels were generally within normal range. The combinations of all pretreatments with enflurane, halothane, or methoxyflurane had the fastest recovery; recovery was slower with the other anesthetic agents, but none of the prior chemotherapeutic drugs accelerated recovery from the inhalation anesthetics.", "contents": "The influence of chronic administration of hypnotics and analgesics on rate of recovery from inhalation anesthesia in rats. A series of groups of Sprague-Dawley rats were given either secobarbital, phenobarbital, morphine, pentazocine, diazepam, methotrimeprazine, or saline (control) intraperitoneally on 4 consecutive days and then, on day 5, anesthetized with chloroform, trichlorethylene, fluroxene, halothane, methoxyflurane, enflurane, isoflurane, bromotrifluorocyclobutane, or chlorotrifluorocyclobutane. One control group received neither pretreatment nor anesthetics and another was given pretreatment but no anesthetics. The factor of \"enzyme induction\" is also evaluated, as are SGPT elevation and liver and kidney lesions. If enzyme induction occurred with the drugs used for pretreatment, the anesthetics suppressed the expected response. SGPT levels were generally within normal range. The combinations of all pretreatments with enflurane, halothane, or methoxyflurane had the fastest recovery; recovery was slower with the other anesthetic agents, but none of the prior chemotherapeutic drugs accelerated recovery from the inhalation anesthetics."}
{"id": "PMID:234705", "title": "Isolation and characterization of an adenovirus and isolation of its adenovirus-associated virus in cell culture from foals with respiratory tract disease.", "content": "An adenovirus was isolated from a foal with respiratory tract disease. The virus produced cytopathic effects (CPE) in equine embryo kidney (EEK) cell culture, contained deoxyribonucleic acid (DNA), was resistant to chloroform and pH 3, and was moderately resistant to heat. The virus caused hemagglutination of human (type O) erythrocytes. Viral density was 1.34 g/cm,3 and diameter was 75 nm. An adenovirus-associated virus (AAV) isolated from the infected cell culture was 22 nm in diameter. These viruses are classified as equine adenovirus and equine AAV.", "contents": "Isolation and characterization of an adenovirus and isolation of its adenovirus-associated virus in cell culture from foals with respiratory tract disease. An adenovirus was isolated from a foal with respiratory tract disease. The virus produced cytopathic effects (CPE) in equine embryo kidney (EEK) cell culture, contained deoxyribonucleic acid (DNA), was resistant to chloroform and pH 3, and was moderately resistant to heat. The virus caused hemagglutination of human (type O) erythrocytes. Viral density was 1.34 g/cm,3 and diameter was 75 nm. An adenovirus-associated virus (AAV) isolated from the infected cell culture was 22 nm in diameter. These viruses are classified as equine adenovirus and equine AAV."}
{"id": "PMID:234698", "title": "Comparative evaluation of a new inhalation anesthetic, BAX-3224, and halothane in Macaca speciosa.", "content": "Two groups of 8 monkeys were anesthetized with either BAX-3224, a new fluorinated methyl-propyl ether, or with halothane, 3 hours daily for a total of 30 hours. Vomiting incidence was 12.5 percent with BAX-3224 during both induction and recovery, compared with 3.7 percent for halothane during induction and 7 percent for halothane during recovery. Induction time did not change during the course of study with either agent. Respiration was spontaneous and cardiopulmonary function was stable. Electroretinographic (ERG) responses were consistent, flicker-light responses similar, but visual evoked responses (VER) were not present during BAX-3224 anesthesia. A 33 percent incidence of electroencephalographic (EEG) silence occurred with BAX-3224, which was consistent with absence of VER. Hematologic and serum chemistry values were similar for both agents. Serum fluoride ion concentrations, measured before exposure and 4 times during the 10-day study, did not change after administration of either agent. This finding was significant for BAX-3224, a fluorinated ether. No cardiac arrhythmias were observed during BAX-3224 anesthesia, compared with a 17 percent incidence during halothane induction. Recovery time was 32 minutes following BAX-3224 and 14 minutes after halothane. BAX-3224 produced anesthesia similar to that of halothane, did not induce changes incompatible with recovery from anesthesia, and showed great potential as a new volatile liquid anesthetic agent with excellent biologic stability.", "contents": "Comparative evaluation of a new inhalation anesthetic, BAX-3224, and halothane in Macaca speciosa. Two groups of 8 monkeys were anesthetized with either BAX-3224, a new fluorinated methyl-propyl ether, or with halothane, 3 hours daily for a total of 30 hours. Vomiting incidence was 12.5 percent with BAX-3224 during both induction and recovery, compared with 3.7 percent for halothane during induction and 7 percent for halothane during recovery. Induction time did not change during the course of study with either agent. Respiration was spontaneous and cardiopulmonary function was stable. Electroretinographic (ERG) responses were consistent, flicker-light responses similar, but visual evoked responses (VER) were not present during BAX-3224 anesthesia. A 33 percent incidence of electroencephalographic (EEG) silence occurred with BAX-3224, which was consistent with absence of VER. Hematologic and serum chemistry values were similar for both agents. Serum fluoride ion concentrations, measured before exposure and 4 times during the 10-day study, did not change after administration of either agent. This finding was significant for BAX-3224, a fluorinated ether. No cardiac arrhythmias were observed during BAX-3224 anesthesia, compared with a 17 percent incidence during halothane induction. Recovery time was 32 minutes following BAX-3224 and 14 minutes after halothane. BAX-3224 produced anesthesia similar to that of halothane, did not induce changes incompatible with recovery from anesthesia, and showed great potential as a new volatile liquid anesthetic agent with excellent biologic stability."}
{"id": "PMID:234706", "title": "Cytomegalovirus pneumonia after human marrow transplantation.", "content": "Thirty-three of 85 patients undergoing marrow transplantation between 1969 and 1973 developed interstitial pneumonia; 23 died. The clinical syndrome consisted of tachypnea, cough, fever, rales, and hypoxemia; the radiologic findings were variable. The development of interstitial pneumonia was significantly associated with graft-versus-host disease and allogenic grafting; patients with isogenic grafts were relatively spared. The increased attack rate between 1969-71 (20%) and 1972-73 (49%) was not fully explained by improved long-term survival, by an increased proportion of allogenic transplants, or by an increased incidence of graft-versus-host disease. Intranuclear inclusions typical of cytomegalovirus were identified in 9 of 17 autopsy-confirmed cases, and patients whose marrow donors had positive cytomegalovirus antibody titers developed interstitial pneumonia more often than patients whose donor had negative titers. Interstitial pneumonia is an important cause of morbidity and mortality after human marrow transplantation. No effective treatment is presently available.", "contents": "Cytomegalovirus pneumonia after human marrow transplantation. Thirty-three of 85 patients undergoing marrow transplantation between 1969 and 1973 developed interstitial pneumonia; 23 died. The clinical syndrome consisted of tachypnea, cough, fever, rales, and hypoxemia; the radiologic findings were variable. The development of interstitial pneumonia was significantly associated with graft-versus-host disease and allogenic grafting; patients with isogenic grafts were relatively spared. The increased attack rate between 1969-71 (20%) and 1972-73 (49%) was not fully explained by improved long-term survival, by an increased proportion of allogenic transplants, or by an increased incidence of graft-versus-host disease. Intranuclear inclusions typical of cytomegalovirus were identified in 9 of 17 autopsy-confirmed cases, and patients whose marrow donors had positive cytomegalovirus antibody titers developed interstitial pneumonia more often than patients whose donor had negative titers. Interstitial pneumonia is an important cause of morbidity and mortality after human marrow transplantation. No effective treatment is presently available."}
{"id": "PMID:234709", "title": "The effect of electromagnetic radiation on the hematopoietic stem cells of mice.", "content": "An increase in the leukocyte number in blood and a decrease in the total cell volume of the bone marrow and spleen were observed in mice after wholebody microwave irradiation (2450 MHz, lambda equals 12.5 cm, 100 mW/cm-2). The number of hematopoietic stem cells increased early after microwave irradiation (1626 plus or minus 53 CFU in bone marrow, 689 plus or minus 86 CFU in the spleen), as compared with that or control (598 plus or minus 92 and 349 plus or minus 79 CFU, respectively). Incorporation of 59Fe in the spleen decreased to 78% of the control value 24 hr after irradiation, which was followed by an increase to 250% on Day 14 after irradiation. After heat exposure, CFUs showed an early decrease in number, whereas the percentage of 59Fe incorporation increased. The different effects of microwaves and externally applied heat on the hematopoietic stem cells suggested that alterations in tissues caused by high-intensity microwave radiation need not be related only to increased internal temperature.", "contents": "The effect of electromagnetic radiation on the hematopoietic stem cells of mice. An increase in the leukocyte number in blood and a decrease in the total cell volume of the bone marrow and spleen were observed in mice after wholebody microwave irradiation (2450 MHz, lambda equals 12.5 cm, 100 mW/cm-2). The number of hematopoietic stem cells increased early after microwave irradiation (1626 plus or minus 53 CFU in bone marrow, 689 plus or minus 86 CFU in the spleen), as compared with that or control (598 plus or minus 92 and 349 plus or minus 79 CFU, respectively). Incorporation of 59Fe in the spleen decreased to 78% of the control value 24 hr after irradiation, which was followed by an increase to 250% on Day 14 after irradiation. After heat exposure, CFUs showed an early decrease in number, whereas the percentage of 59Fe incorporation increased. The different effects of microwaves and externally applied heat on the hematopoietic stem cells suggested that alterations in tissues caused by high-intensity microwave radiation need not be related only to increased internal temperature."}
{"id": "PMID:234712", "title": "Continuous monitoring of pH and Eh in bacterial plaque grown on a tooth in an artificial mouth.", "content": "Apparatus which enables the simultaneous continuous monitoring of pH and Eh of bacterial dental plaque as it develops on a tooth surface in an artificial mouth is described.  Details of the electrodes used, monitoring equipment, and culture conditions are given.  Preliminary results are given showing the Eh and pH values of plaque produced in vitro to be in close agreement with readings reported for plaque in vivo.  The effect of the incorporation of 1 per cent sucrose in the medium on these parameters is reported and a distinct inverse relationship between pH and Eh recorded.", "contents": "Continuous monitoring of pH and Eh in bacterial plaque grown on a tooth in an artificial mouth. Apparatus which enables the simultaneous continuous monitoring of pH and Eh of bacterial dental plaque as it develops on a tooth surface in an artificial mouth is described.  Details of the electrodes used, monitoring equipment, and culture conditions are given.  Preliminary results are given showing the Eh and pH values of plaque produced in vitro to be in close agreement with readings reported for plaque in vivo.  The effect of the incorporation of 1 per cent sucrose in the medium on these parameters is reported and a distinct inverse relationship between pH and Eh recorded."}
{"id": "PMID:234713", "title": "Dichlorofluoromethane inactivates Saccharomyces cerevisiae.", "content": "Saccharomyces cerevisiae was incubated in aerosol cans containing YM broth and dichlorofluoromethane (f-21). The presence and number of viable cells were determined by inoculating (1% vol/vol) YM broth and by the plate count procedure (YM agar). Inactivation of the yeast was greater or more rapid when: (i) the thermodynamic activity (saturation value) of f-21 became greater through increasing the concentration of chemical from 0.5 to 1.5% (wt/wt) in a given volume (20, 40, or 80 ml) of broth, or by holding the concentration of chemical constant but increasing the volume of broth in the test vessel, (ii) the temperature of treatment was increased (7, 22, 37, and 47 C), (iii) samples with 1.5% (wt/wt) f-21 were agitated, (iv) young (8 h) rather than old (36 h or 10 days) cells were treated, and (v) cells were grown in YM broth without, rather than with, glucose. Adjusting the pH (6.3 to 4.0) of broth before treatment, pretreating the substrate with f-21, or distilling the chemical before use had no effect on viability of cells when treated with f-21. Yeast cells inactivated by f-21, chlorine, or heat were more resistant to disruption by sonic treatment than were viable cells.", "contents": "Dichlorofluoromethane inactivates Saccharomyces cerevisiae. Saccharomyces cerevisiae was incubated in aerosol cans containing YM broth and dichlorofluoromethane (f-21). The presence and number of viable cells were determined by inoculating (1% vol/vol) YM broth and by the plate count procedure (YM agar). Inactivation of the yeast was greater or more rapid when: (i) the thermodynamic activity (saturation value) of f-21 became greater through increasing the concentration of chemical from 0.5 to 1.5% (wt/wt) in a given volume (20, 40, or 80 ml) of broth, or by holding the concentration of chemical constant but increasing the volume of broth in the test vessel, (ii) the temperature of treatment was increased (7, 22, 37, and 47 C), (iii) samples with 1.5% (wt/wt) f-21 were agitated, (iv) young (8 h) rather than old (36 h or 10 days) cells were treated, and (v) cells were grown in YM broth without, rather than with, glucose. Adjusting the pH (6.3 to 4.0) of broth before treatment, pretreating the substrate with f-21, or distilling the chemical before use had no effect on viability of cells when treated with f-21. Yeast cells inactivated by f-21, chlorine, or heat were more resistant to disruption by sonic treatment than were viable cells."}
{"id": "PMID:234714", "title": "Production and purification of the thermophilic bacteriophage TP-84.", "content": "A new procedure for production and purification of the thermophilic bacteriophage TP-84 in high yields is described. Cultures of Bacillus stearothermophilus strain 10, enriched with nutrients to obtain heavy growth and to prevent sporulation and maintained at a pH of 6.5, were infected with the phage in a 100-liter fermentor.  Addition of magnesium chloride (0.01 M) and a temperature of 58-C were essential for maximal phage production.  Phage (5 times 1011 infective particles/ml) was precipitated with polyethylene glycol (molecular weight 6,000) in the presence of sodium chloride and was further purified by cesium chloride density centrifugation.", "contents": "Production and purification of the thermophilic bacteriophage TP-84. A new procedure for production and purification of the thermophilic bacteriophage TP-84 in high yields is described. Cultures of Bacillus stearothermophilus strain 10, enriched with nutrients to obtain heavy growth and to prevent sporulation and maintained at a pH of 6.5, were infected with the phage in a 100-liter fermentor.  Addition of magnesium chloride (0.01 M) and a temperature of 58-C were essential for maximal phage production.  Phage (5 times 1011 infective particles/ml) was precipitated with polyethylene glycol (molecular weight 6,000) in the presence of sodium chloride and was further purified by cesium chloride density centrifugation."}
{"id": "PMID:234715", "title": "Adsorption of Vibrio parahaemolyticus onto chitin and copepods.", "content": "Vibrio parahaemolyticus was observed to adsorb onto chitin particles and copepods.  The efficiency of adsorption was found to be dependent on pH and on the concentration of NaC1 and other ions found in seawater.  Highest efficiency was observed in water samples collected from Chesapeake Bay and lowest in water from the open sea.  V. parahaemolyticus was found to adborb onto chitin with the highest efficiency of the several bacterial strains tested.  Escherichia coli and Pseudomonas fluorescens did not adsorb onto chitin.  The adsorption effect is considered to be one of the major factors determining the distribution of this species and affecting the annual cycle of V. parahaemolyticus in the estuarine system.", "contents": "Adsorption of Vibrio parahaemolyticus onto chitin and copepods. Vibrio parahaemolyticus was observed to adsorb onto chitin particles and copepods.  The efficiency of adsorption was found to be dependent on pH and on the concentration of NaC1 and other ions found in seawater.  Highest efficiency was observed in water samples collected from Chesapeake Bay and lowest in water from the open sea.  V. parahaemolyticus was found to adborb onto chitin with the highest efficiency of the several bacterial strains tested.  Escherichia coli and Pseudomonas fluorescens did not adsorb onto chitin.  The adsorption effect is considered to be one of the major factors determining the distribution of this species and affecting the annual cycle of V. parahaemolyticus in the estuarine system."}
{"id": "PMID:234716", "title": "Effect of L-histidine on the survival of a T-strain of mycoplasma.", "content": "The addition of L-histidine to the growth medium prolongs the stationary phase and the survival of a T-strain of mycoplasma. Results of an experiment performed with (14)C-labeled urea demonstrate that the action of L-histidine is based on the retardation of the rise of pH.", "contents": "Effect of L-histidine on the survival of a T-strain of mycoplasma. The addition of L-histidine to the growth medium prolongs the stationary phase and the survival of a T-strain of mycoplasma. Results of an experiment performed with (14)C-labeled urea demonstrate that the action of L-histidine is based on the retardation of the rise of pH."}
{"id": "PMID:234717", "title": "Use of pH gradient plates for increasing the acid tolerance of salmonellae.", "content": "Several strains of salmonellae survived higher concentrations of lactic acid after streaking on the surface of pH gradient plates. Most strains increased their acid tolerance by about 0.8 to 1.0 pH unit (9-to 10-fold), with Salmonella madelia showing the greatest differential, pH 5.2 in the wild strain and pH 4.2 after conditioning. The increased acid resistance was quickly lost after transferring to normal tryptic soy agar. Tests for survival in a liquid medium at pH values lower than those giving visible growth indicated that these pH values were bactericidal rather than bacteriostatic for both the wild and acid-conditioned strains.", "contents": "Use of pH gradient plates for increasing the acid tolerance of salmonellae. Several strains of salmonellae survived higher concentrations of lactic acid after streaking on the surface of pH gradient plates. Most strains increased their acid tolerance by about 0.8 to 1.0 pH unit (9-to 10-fold), with Salmonella madelia showing the greatest differential, pH 5.2 in the wild strain and pH 4.2 after conditioning. The increased acid resistance was quickly lost after transferring to normal tryptic soy agar. Tests for survival in a liquid medium at pH values lower than those giving visible growth indicated that these pH values were bactericidal rather than bacteriostatic for both the wild and acid-conditioned strains."}
{"id": "PMID:234718", "title": "Metabolism of glutamic acid in Aspergillus ochraceus during the biosynthesis of ochratoxin A.", "content": "The uptake and utilization of glutamic acid in the biosynthesis of ochratoxin A by Aspergillus ochraceus were studied. Uniformly labeled L[14C]glutamic acid was incorporated into both the phenylalanine and isocoumarin moieties of ochratoxin A. Penicillic acid was also labeled. During the early stages of development, the amino acid was used mainly for the synthesis of ribonucleic acid and protein. A portion of glutamic acid was oxidized and was recovered as metabolic 14CO-2. The initial uptake  velocity of glutamic acid decreased with age and was pH and temperature dependent. No relationship was found between the initial uptake velocities and ochratoxin A biosynthesis.", "contents": "Metabolism of glutamic acid in Aspergillus ochraceus during the biosynthesis of ochratoxin A. The uptake and utilization of glutamic acid in the biosynthesis of ochratoxin A by Aspergillus ochraceus were studied. Uniformly labeled L[14C]glutamic acid was incorporated into both the phenylalanine and isocoumarin moieties of ochratoxin A. Penicillic acid was also labeled. During the early stages of development, the amino acid was used mainly for the synthesis of ribonucleic acid and protein. A portion of glutamic acid was oxidized and was recovered as metabolic 14CO-2. The initial uptake  velocity of glutamic acid decreased with age and was pH and temperature dependent. No relationship was found between the initial uptake velocities and ochratoxin A biosynthesis."}
{"id": "PMID:234719", "title": "Powdered chitin agar as a selective medium for enumeration of actinomycetes in water and soil.", "content": "Agar media made with 0.4% colloidal chitin plus mineral salts and adjusted to pH 8.0 was superior to four other commonly used media for the isolation and enumeration of actinomycetes from water samples. More actinomycetes developed on chitin agar, and the development of bacteria and fungi was suppressed. Frozen and vacuum-dried chitin from aqueous colloidal suspensions was finely divided and gave results comparable to those obtained with media prepared from colloidal suspensions.", "contents": "Powdered chitin agar as a selective medium for enumeration of actinomycetes in water and soil. Agar media made with 0.4% colloidal chitin plus mineral salts and adjusted to pH 8.0 was superior to four other commonly used media for the isolation and enumeration of actinomycetes from water samples. More actinomycetes developed on chitin agar, and the development of bacteria and fungi was suppressed. Frozen and vacuum-dried chitin from aqueous colloidal suspensions was finely divided and gave results comparable to those obtained with media prepared from colloidal suspensions."}
{"id": "PMID:234720", "title": "Effect of prednisolon on cell metabolism of candida.", "content": "In vitro effects of 2 water-soluble prednisolon-derivatives on 10 Candida albicans and 10 Candida tropicals species were investigated. Tests were performed during resting and proliferation phases. Changes of cell metabolism were measured by O2-consumption by the Warburg technique. With increasing corticosteroid concentrations (10-10000 gammaml) a dose dependent increase of cell respiration was found with and without addition of nutritive substrates. Even high concentrations of corticosteroid did not cause an antimetabolic effect. The tests did not yield different results for the two Candida species examined.", "contents": "Effect of prednisolon on cell metabolism of candida. In vitro effects of 2 water-soluble prednisolon-derivatives on 10 Candida albicans and 10 Candida tropicals species were investigated. Tests were performed during resting and proliferation phases. Changes of cell metabolism were measured by O2-consumption by the Warburg technique. With increasing corticosteroid concentrations (10-10000 gammaml) a dose dependent increase of cell respiration was found with and without addition of nutritive substrates. Even high concentrations of corticosteroid did not cause an antimetabolic effect. The tests did not yield different results for the two Candida species examined."}
{"id": "PMID:234721", "title": "The behaviour of collagen peptidase in the serum of different dermatoses.", "content": "In 150 patients with different dermatoses and 15 controls the activity of collagen peptidase in serum was determined. No relation to specific skin diseases was found. Negative findings were also observed in the group of collagenoses: only 4 of 14 patients with progressive systemic sclerosis showed an increase of this enzyme activity. These negative results seem noteworthy because it thus is demonstrated that alterations of collagen structure are not necessaryly associated with alterations of collagen peptidase activity.", "contents": "The behaviour of collagen peptidase in the serum of different dermatoses. In 150 patients with different dermatoses and 15 controls the activity of collagen peptidase in serum was determined. No relation to specific skin diseases was found. Negative findings were also observed in the group of collagenoses: only 4 of 14 patients with progressive systemic sclerosis showed an increase of this enzyme activity. These negative results seem noteworthy because it thus is demonstrated that alterations of collagen structure are not necessaryly associated with alterations of collagen peptidase activity."}
{"id": "PMID:234722", "title": "DDT and immunological responses. 3. Reduced anaphylaxis and mast cell population in rats fed DDT.", "content": "Previous work showed that anaphylaxis, mast cell population, and tissue histamine content are reduced in guinea pigs given DDT injections. This study was intended to determine whether dietary intake of DDT causes similar effects. Rats immunized with diphtheria toxoid and fed diets containing DDT at 20 and 200 ppm levels for 31 days did not show effects on their serum antitoxin titers, but the numbers of metachromatically stained, histamine-containing mast cells in mesenteries were reduced: in the 20 ppm group by 46% and in the 200 ppm group by 61%. The severity of anaphylactic shock was also reduced in proportion to the DDT dietary levels, and, thus, the magnitude of mast cells. Apparently, daily dietary DDT intake above 2.2 mg DDT/kg of body weight alters the physiology of mast cells in the rat, and thus affects histamine-mediated reactions.", "contents": "DDT and immunological responses. 3. Reduced anaphylaxis and mast cell population in rats fed DDT. Previous work showed that anaphylaxis, mast cell population, and tissue histamine content are reduced in guinea pigs given DDT injections. This study was intended to determine whether dietary intake of DDT causes similar effects. Rats immunized with diphtheria toxoid and fed diets containing DDT at 20 and 200 ppm levels for 31 days did not show effects on their serum antitoxin titers, but the numbers of metachromatically stained, histamine-containing mast cells in mesenteries were reduced: in the 20 ppm group by 46% and in the 200 ppm group by 61%. The severity of anaphylactic shock was also reduced in proportion to the DDT dietary levels, and, thus, the magnitude of mast cells. Apparently, daily dietary DDT intake above 2.2 mg DDT/kg of body weight alters the physiology of mast cells in the rat, and thus affects histamine-mediated reactions."}
{"id": "PMID:234723", "title": "Different behaviors of erythrocyte delta-aminolevulinic acid dehydratase. A comparison study between lead workers and normals.", "content": "Different characteristics of erythrocyte delta-aminolevulinic acid dehydratase (ALA-D1) between the workers with the history of occupational lead exposure and normals are described. In the blood of lead workers, when the hemolysates are heated at 60 C for five minutes, the activity of the erythrocytes ALA-D increases up to about 3.6-fold of an initial level, and as a result of heating the optimum in pH-activity curvee changes from pH 6.0 to pH 6.6, which is similar to the optimum pH of normal ALA-D. On the contrary, in normal blood, the optimum in the pH-activity curve is but little changed, even though the erythrocyte ALA-D activity is increased up to about 1.3-fold of the initial level by heating the hemolysates at 60 C for five minutes.", "contents": "Different behaviors of erythrocyte delta-aminolevulinic acid dehydratase. A comparison study between lead workers and normals. Different characteristics of erythrocyte delta-aminolevulinic acid dehydratase (ALA-D1) between the workers with the history of occupational lead exposure and normals are described. In the blood of lead workers, when the hemolysates are heated at 60 C for five minutes, the activity of the erythrocytes ALA-D increases up to about 3.6-fold of an initial level, and as a result of heating the optimum in pH-activity curvee changes from pH 6.0 to pH 6.6, which is similar to the optimum pH of normal ALA-D. On the contrary, in normal blood, the optimum in the pH-activity curve is but little changed, even though the erythrocyte ALA-D activity is increased up to about 1.3-fold of the initial level by heating the hemolysates at 60 C for five minutes."}
{"id": "PMID:234725", "title": "The fate of autologous fascia lata grafts in dogs.", "content": "The fate of tricuspid fascia lata valves and intracardiac grafts was studied morphologically, histologically, and biochemically in dogs. Severe degenerative changes occurring by 21 days were largely correlated with graft thickening due to gross endothelialization. A primary event in graft alteration was an initial loss of the indigenous fibroblast population as detected both microscopically and by autoradiography after pulse labeling with 14C-Nethylmaleimide. Using different isotopic labeling procedures, both the in vivo and in vitro graft degradation patterns demonstrated that a second early eft degradation was correlated in vivo with endothelialization and collagenase secretion by invasive cells.", "contents": "The fate of autologous fascia lata grafts in dogs. The fate of tricuspid fascia lata valves and intracardiac grafts was studied morphologically, histologically, and biochemically in dogs. Severe degenerative changes occurring by 21 days were largely correlated with graft thickening due to gross endothelialization. A primary event in graft alteration was an initial loss of the indigenous fibroblast population as detected both microscopically and by autoradiography after pulse labeling with 14C-Nethylmaleimide. Using different isotopic labeling procedures, both the in vivo and in vitro graft degradation patterns demonstrated that a second early eft degradation was correlated in vivo with endothelialization and collagenase secretion by invasive cells."}
{"id": "PMID:234726", "title": "The hysterical personality. An attempt at validation with the MMPI.", "content": "We attempted to validate the DSM-II diagnosis of hysterical personality and the depression often experienced by such patients by comparing mean Minnesota Multiphasic Personality inventory (MMP) scores of hysterical personality patients with those of paranoid schizophrenic patients and a group with mixed psychiatric diagnoses. Index patients had significantly higher scores than either control group and could be distinguished on individual scales from the paranoid schizophrenics. However, the mean MMPl profile of hysterical personalities was similar to that of depressed controls. Therefore, the MMPl alone could not differentiate these two groups nor could it confirm or refute the validity of the diagnostic concept of hysterical personality, but it did support the clinical observation that depression is a major risk for individuals given this diagnosis and that the experience of depression by these patients is genuine.", "contents": "The hysterical personality. An attempt at validation with the MMPI. We attempted to validate the DSM-II diagnosis of hysterical personality and the depression often experienced by such patients by comparing mean Minnesota Multiphasic Personality inventory (MMP) scores of hysterical personality patients with those of paranoid schizophrenic patients and a group with mixed psychiatric diagnoses. Index patients had significantly higher scores than either control group and could be distinguished on individual scales from the paranoid schizophrenics. However, the mean MMPl profile of hysterical personalities was similar to that of depressed controls. Therefore, the MMPl alone could not differentiate these two groups nor could it confirm or refute the validity of the diagnostic concept of hysterical personality, but it did support the clinical observation that depression is a major risk for individuals given this diagnosis and that the experience of depression by these patients is genuine."}
{"id": "PMID:234727", "title": "The offspring of schizophrenics. Fetal and neonatal deaths.", "content": "This is the first report in a projected series on neurological development among the offspring of schizophernics. An increased incidence of fetal and neonatal deaths is noted among offspring of schizophrenics when compared to a closely matched control group, using data collected prospectively. In many cases, no apparent reason for death was determined; in some cases, major neurological malformations were found. It is necessary to consider three possible explantions for these findings--genotype of the child, adverse intrauterine environment, and medication toxicity.", "contents": "The offspring of schizophrenics. Fetal and neonatal deaths. This is the first report in a projected series on neurological development among the offspring of schizophernics. An increased incidence of fetal and neonatal deaths is noted among offspring of schizophrenics when compared to a closely matched control group, using data collected prospectively. In many cases, no apparent reason for death was determined; in some cases, major neurological malformations were found. It is necessary to consider three possible explantions for these findings--genotype of the child, adverse intrauterine environment, and medication toxicity."}
{"id": "PMID:234728", "title": "Supervision of the initial interview. A study of two methods.", "content": "Two methods of supervision of the initial evaluation of outpatients by psychiatric residents were compared. In condition 1, residents evaluated patients and then presented the case material to a supervisor in the traditional manner. In condition 2, the supervisor observed the interview directly. Supervisor and residents then independently completed ratings of psychopathology, motivation, insight, and prognosis of the patients. Significant differences in several variables between the two conditions were noted. Resident and supervisor ratings of patients were in clear agreement when both observed the interview.", "contents": "Supervision of the initial interview. A study of two methods. Two methods of supervision of the initial evaluation of outpatients by psychiatric residents were compared. In condition 1, residents evaluated patients and then presented the case material to a supervisor in the traditional manner. In condition 2, the supervisor observed the interview directly. Supervisor and residents then independently completed ratings of psychopathology, motivation, insight, and prognosis of the patients. Significant differences in several variables between the two conditions were noted. Resident and supervisor ratings of patients were in clear agreement when both observed the interview."}
{"id": "PMID:234730", "title": "Cardiorespiratory responses to dextran 40. Hemodynamic and oxygen transport changes in normal subjects and critically ill patients.", "content": "Hemodynamic and oxygen transport were observed in 190 studies before and after administration of 500 ml dextran 40 in 12 normal, healthy subjects and 147 critically ill patients who were, or recently had been, in various degrees of shock. The major influence of dextran 40 was plasma expansion and hemodilution, which resulted in increased blood flow and blood volume. In general, the pressure-flow responses were greater in the ill patients than in the normal subjects. After dextran 40 infusion, oxygen transport increased in the critically ill patients, but not in the normal volunteers. Some of the effects of dextran 40 on oxygen transport in critically ill patients may be attributed to increased tissue perfusion from expansion of plasma volume, as well as to improved flow properties of blood in the microcirculation.", "contents": "Cardiorespiratory responses to dextran 40. Hemodynamic and oxygen transport changes in normal subjects and critically ill patients. Hemodynamic and oxygen transport were observed in 190 studies before and after administration of 500 ml dextran 40 in 12 normal, healthy subjects and 147 critically ill patients who were, or recently had been, in various degrees of shock. The major influence of dextran 40 was plasma expansion and hemodilution, which resulted in increased blood flow and blood volume. In general, the pressure-flow responses were greater in the ill patients than in the normal subjects. After dextran 40 infusion, oxygen transport increased in the critically ill patients, but not in the normal volunteers. Some of the effects of dextran 40 on oxygen transport in critically ill patients may be attributed to increased tissue perfusion from expansion of plasma volume, as well as to improved flow properties of blood in the microcirculation."}
{"id": "PMID:234731", "title": "Survivor's and nonsurvivors' responses to dextran 40. Hemodynamic and oxygen transport changes in critically ill patients.", "content": "Cardiorespiratory effects of dextran 40 administration were measured and compared retrospectively in 74 surviving and 73 nonsurviving critically ill patients. In the preinfusion control period, the survivors had higher mean arterial pressures and blood flow with lesser blood volume deficits. Dextran significantly improved pressure, blood flow, blood volume, oxygen transport, and derived calculations in both groups, but the average cardiorespiratory responses to dextran were somewhat greater in nonsurvivors than in survivors, About two thirds of the patients responded to dextran with significantly increased oxygen consumption (P smaller than .05), suggesting that this agent improved oxygen transport by its rheologic effects on the microcirculation. The cardiorespiratory effects of dextran were slightly greater in the patients who ultimately died; nevertheless, the salutary cardiorespiratory response did not reverse the clinical course in nonsurvivors, whose perfusion defect apparently had reached irreversible proportions prior to the administration of the drug.", "contents": "Survivor's and nonsurvivors' responses to dextran 40. Hemodynamic and oxygen transport changes in critically ill patients. Cardiorespiratory effects of dextran 40 administration were measured and compared retrospectively in 74 surviving and 73 nonsurviving critically ill patients. In the preinfusion control period, the survivors had higher mean arterial pressures and blood flow with lesser blood volume deficits. Dextran significantly improved pressure, blood flow, blood volume, oxygen transport, and derived calculations in both groups, but the average cardiorespiratory responses to dextran were somewhat greater in nonsurvivors than in survivors, About two thirds of the patients responded to dextran with significantly increased oxygen consumption (P smaller than .05), suggesting that this agent improved oxygen transport by its rheologic effects on the microcirculation. The cardiorespiratory effects of dextran were slightly greater in the patients who ultimately died; nevertheless, the salutary cardiorespiratory response did not reverse the clinical course in nonsurvivors, whose perfusion defect apparently had reached irreversible proportions prior to the administration of the drug."}
{"id": "PMID:234732", "title": "Catecholamines in experimental brain ischemia.", "content": "Local cerebral ischemia was produced in rats by internal carotid artery injection of 35 mu carbon microspheres, and brain norepinephrine (NE), dopamine, and cyclic adenosine 3, 5-monophosphate (cAMP) were measured in embolized and intact hemispheres at intervals up to four hours. Sham-operated animals were controls. There was an instantaneous increase of cAMP. Norepinephrine was reduced within two minutes after embolization and remained low for four hours. Dopamine increased by five minutes after embolization and returned to normal after four hours. Results were qualitatively similar, but less, in the nonembolized hemisphere. Accumulation of cAMP is thought to be due to a direct effect of ischemic hypoxia and may be the initiating factor in increased glycolysis that occurs in ischemia. Decrease in NE may be secondary to its generalized release from presynaptic terminals throughout the brain and could be a factor in cortical vasocontriction that follows embolization. Dopamine changes are a reflection of alterations in energy metabolism.", "contents": "Catecholamines in experimental brain ischemia. Local cerebral ischemia was produced in rats by internal carotid artery injection of 35 mu carbon microspheres, and brain norepinephrine (NE), dopamine, and cyclic adenosine 3, 5-monophosphate (cAMP) were measured in embolized and intact hemispheres at intervals up to four hours. Sham-operated animals were controls. There was an instantaneous increase of cAMP. Norepinephrine was reduced within two minutes after embolization and remained low for four hours. Dopamine increased by five minutes after embolization and returned to normal after four hours. Results were qualitatively similar, but less, in the nonembolized hemisphere. Accumulation of cAMP is thought to be due to a direct effect of ischemic hypoxia and may be the initiating factor in increased glycolysis that occurs in ischemia. Decrease in NE may be secondary to its generalized release from presynaptic terminals throughout the brain and could be a factor in cortical vasocontriction that follows embolization. Dopamine changes are a reflection of alterations in energy metabolism."}
{"id": "PMID:234733", "title": "Amino acid composition of cerebrospinal fluid in actue neuroinfections in children.", "content": "A survey of the cerebrospinal fluid (CSF) amino acids, glutamine, and glutamic and gamma-aminobutyric (GABA) acids was made in 168 children, aged 1 to 14 years, with various neurological infections. The glutamic acid and glutamine concentrations in the CSF of children with severe forms of acute serous and bacterial meningitis were about three to four times as great as in controls. The indices returned almost to normal during recovery. GABA is absent in normal CSF, but appeared in the CSF of patients with bacterial meningitis. Its determination may be used as an additional test to differentiate between serous and bacterial meningitis.", "contents": "Amino acid composition of cerebrospinal fluid in actue neuroinfections in children. A survey of the cerebrospinal fluid (CSF) amino acids, glutamine, and glutamic and gamma-aminobutyric (GABA) acids was made in 168 children, aged 1 to 14 years, with various neurological infections. The glutamic acid and glutamine concentrations in the CSF of children with severe forms of acute serous and bacterial meningitis were about three to four times as great as in controls. The indices returned almost to normal during recovery. GABA is absent in normal CSF, but appeared in the CSF of patients with bacterial meningitis. Its determination may be used as an additional test to differentiate between serous and bacterial meningitis."}
{"id": "PMID:234734", "title": "Postmortem changes in brain catecholamine enzymes.", "content": "Postmortem changes in the activities of tyrosine hydroxylase, dopa decarboxylase, and dopamine-beta-hydroxylase were examined in various areas of rat brain. Tyrosine hydroxylase activity decreased in an exponential fashion with a half-time of two to four hours in caudate-putamen, substantia nigra, and locus ceruleus. Dopa decarboxylase activity remained within 20% of control values at five hours in these areas, but then decreased precipitously. Dopamine-beta-hydroxylase activity remained within 20% of control for at least 20 hours after death.", "contents": "Postmortem changes in brain catecholamine enzymes. Postmortem changes in the activities of tyrosine hydroxylase, dopa decarboxylase, and dopamine-beta-hydroxylase were examined in various areas of rat brain. Tyrosine hydroxylase activity decreased in an exponential fashion with a half-time of two to four hours in caudate-putamen, substantia nigra, and locus ceruleus. Dopa decarboxylase activity remained within 20% of control values at five hours in these areas, but then decreased precipitously. Dopamine-beta-hydroxylase activity remained within 20% of control for at least 20 hours after death."}
{"id": "PMID:234735", "title": "Microbiological sampling of the spacecraft atmosphere during a simulated skylab mission.", "content": "A skylab Air Sampler (SAS) has been developed for the use during Skylab missions. The SAS was used in the Skylab Medical Experiments Altitude Test (SMEAT) to gather baseline data which could be directly compared to data obtained during actual Skylab missions. The results obtained in the SMEAT gave no evidence of consistent change in either concentration or types of microorganisms in the SMEAT atmosphere over the 56-d test. Microorganisms found included some potential pathogens but were largely normal human microflora. Few typical soil microorganisms were found. These findings are related to commonly anticipated effects of long-term spaceflights on environmental microflora and to other closed environment studies.", "contents": "Microbiological sampling of the spacecraft atmosphere during a simulated skylab mission. A skylab Air Sampler (SAS) has been developed for the use during Skylab missions. The SAS was used in the Skylab Medical Experiments Altitude Test (SMEAT) to gather baseline data which could be directly compared to data obtained during actual Skylab missions. The results obtained in the SMEAT gave no evidence of consistent change in either concentration or types of microorganisms in the SMEAT atmosphere over the 56-d test. Microorganisms found included some potential pathogens but were largely normal human microflora. Few typical soil microorganisms were found. These findings are related to commonly anticipated effects of long-term spaceflights on environmental microflora and to other closed environment studies."}
{"id": "PMID:234736", "title": "Solubility and net exchange of calcium, magnesium and phosphorus in digesta flowing along the gut of the sheep.", "content": "1. The changes in the solubility of calcium, magnesium and phosphorus in digesta flowing along the intestinal tract and the net movement across the intestinal wall of these elements were determined in six rams, each equipped with three T-shaped cannulas; cannulas were placed in a total of six different sites of the small intestine. Cr2O3 was used as a marker substance to measure the rate of flow of the digesta. 2. The concentrations of soluble Ca, Mg and P decreased as digesta moved along the intestine. TheMgreatest fall in soluble Ca occurred after the first 3 m of the intestine, while a significant decrease in soluble Mg was found only at 15 and 25 m from the pylorus. The concentration of soluble P in digesta decreased until the 7 m site and then remained stable. In the faeces, the level of soluble Mg was approximately 4 times higher than, and that of Ca equal to, the levels of Mg and Ca found in digesta flowing through the upper intestine. Unlike Ca and Mg, a very low concentration of soluble P was found in the faeces. 3. In the duodenum, 84, 78 and 62% of the total Ca, Mg and P respectively were soluble, whereas in the digesta flowing through the terminal ileum the corresponding values were 3-2, 7-2 and 19% for Ca, Mg and P respectively. 4. The forestomachs and the colon were found to be the main sites of  g net absorption; 1-12 mmol/h was apparently absorbed from the stomach and 1-05 mmol/h from the colon. The supper small intestine (1-3 m from the pylorus) appeared to be the major site of Ca and P absorption. 5. In the last 10 m of the small intestine, considerable amounts of minerals were secreted; 4-70, 0-96 and 1-85 mmol Ca, Mg and P/h respectively were added to the digesta flowing between 15 and 25 m from the pylorus. The effect of the increase in the pH of digesta along the small intestine on the solubility of these minerals is discussed.", "contents": "Solubility and net exchange of calcium, magnesium and phosphorus in digesta flowing along the gut of the sheep. 1. The changes in the solubility of calcium, magnesium and phosphorus in digesta flowing along the intestinal tract and the net movement across the intestinal wall of these elements were determined in six rams, each equipped with three T-shaped cannulas; cannulas were placed in a total of six different sites of the small intestine. Cr2O3 was used as a marker substance to measure the rate of flow of the digesta. 2. The concentrations of soluble Ca, Mg and P decreased as digesta moved along the intestine. TheMgreatest fall in soluble Ca occurred after the first 3 m of the intestine, while a significant decrease in soluble Mg was found only at 15 and 25 m from the pylorus. The concentration of soluble P in digesta decreased until the 7 m site and then remained stable. In the faeces, the level of soluble Mg was approximately 4 times higher than, and that of Ca equal to, the levels of Mg and Ca found in digesta flowing through the upper intestine. Unlike Ca and Mg, a very low concentration of soluble P was found in the faeces. 3. In the duodenum, 84, 78 and 62% of the total Ca, Mg and P respectively were soluble, whereas in the digesta flowing through the terminal ileum the corresponding values were 3-2, 7-2 and 19% for Ca, Mg and P respectively. 4. The forestomachs and the colon were found to be the main sites of  g net absorption; 1-12 mmol/h was apparently absorbed from the stomach and 1-05 mmol/h from the colon. The supper small intestine (1-3 m from the pylorus) appeared to be the major site of Ca and P absorption. 5. In the last 10 m of the small intestine, considerable amounts of minerals were secreted; 4-70, 0-96 and 1-85 mmol Ca, Mg and P/h respectively were added to the digesta flowing between 15 and 25 m from the pylorus. The effect of the increase in the pH of digesta along the small intestine on the solubility of these minerals is discussed."}
{"id": "PMID:234737", "title": "Environment and conformation dependent sensitivity of the arsanilazotyrosine-248 carboxypeptidase A chromophore.", "content": "Reaction of carboxypeptidase A crystals with diazotized arsanilic acid uniquely modifies Tyr-248 to form a monazo derivative, which-in solution-forms an intramolecular inner-sphere coordination complex in the active site zinc atom. tarsanilazocarboxypeptidase exhibits spectral properties that are closely similar to those of the model complex, tetrazolylazo-N-carbobenzoxytyrosine Zn2+, with a distinctive maximum at 510 nm. In addition, its circular dichroic spectrum reveals a negative extremum at this wavelength, also characteristic of this complex. Both spectra are exquisitely responsive to pth changes and serve to monitor formation and dissociation of the metal-azophenol complex. Two pKapp at 7.7 and 9.5 delineate the pH range over which the probe characteristics most effectively gauge conformational features of the active center of arsanilazcarboxypeptidase. Other environmental parameters, e.g., substrates and inhibitors, as well as crystallization of the enzyme also critically influence the formation and dissociation of the complex; the response of the probe suggests that they induce conformational movement of the azoTyr-248 residue away from the zinc atom. tthe now available chemical, functional, structural data bearing on the spatial relationships of Tyr-248 and Zn, both thought critical to catalysis, are evaluated, based on spectra of arsanilazo- and nitrocarboxypeptidase crystals and solutions as well as on detailed kinetic analyses of the native enzyme in both physical states and based on the X-ray structure analysis of the native enzyme and its Gly-L-Tyr complex. Collectively all of the data show that the conformation of carboxypeptidase in crystals differs from that in solution. Moreover, reexamination of the original X-ray maps reported in 1968 and thought to preclude a Tyr-248-Zn interaction now leads to the conclusion that in up to 25 per cent of the molecules in the crystals ttyr-248 interacts with the active site zinc atom (W.D. Lipscomb (1973), Proc. Nat. Acad. Sci U.S. 70, 3797). Thus, even in the crystals the enzyme exists in at least two different conformations. In one of these Tyr-248 is near while in the other it is far from the zinc atom. The spectral effects of Gly-L-Tyr and beta-phenylpropionate on solutions of arsanilazo- and of nitrocarboxypeptidase demonstrate that during the catalytic process Tyr-248 moves away from the zinc atom. This implies a mechanistic role for Tyr-248 different from that postulated on the basis of X-ray crystallographic analysis. Indeed, the proximity of ttyr-248 to the zinc atom, when altered by substrates and inhibitor, may reflect certain of the properties characteristic of the entatic, active site.", "contents": "Environment and conformation dependent sensitivity of the arsanilazotyrosine-248 carboxypeptidase A chromophore. Reaction of carboxypeptidase A crystals with diazotized arsanilic acid uniquely modifies Tyr-248 to form a monazo derivative, which-in solution-forms an intramolecular inner-sphere coordination complex in the active site zinc atom. tarsanilazocarboxypeptidase exhibits spectral properties that are closely similar to those of the model complex, tetrazolylazo-N-carbobenzoxytyrosine Zn2+, with a distinctive maximum at 510 nm. In addition, its circular dichroic spectrum reveals a negative extremum at this wavelength, also characteristic of this complex. Both spectra are exquisitely responsive to pth changes and serve to monitor formation and dissociation of the metal-azophenol complex. Two pKapp at 7.7 and 9.5 delineate the pH range over which the probe characteristics most effectively gauge conformational features of the active center of arsanilazcarboxypeptidase. Other environmental parameters, e.g., substrates and inhibitors, as well as crystallization of the enzyme also critically influence the formation and dissociation of the complex; the response of the probe suggests that they induce conformational movement of the azoTyr-248 residue away from the zinc atom. tthe now available chemical, functional, structural data bearing on the spatial relationships of Tyr-248 and Zn, both thought critical to catalysis, are evaluated, based on spectra of arsanilazo- and nitrocarboxypeptidase crystals and solutions as well as on detailed kinetic analyses of the native enzyme in both physical states and based on the X-ray structure analysis of the native enzyme and its Gly-L-Tyr complex. Collectively all of the data show that the conformation of carboxypeptidase in crystals differs from that in solution. Moreover, reexamination of the original X-ray maps reported in 1968 and thought to preclude a Tyr-248-Zn interaction now leads to the conclusion that in up to 25 per cent of the molecules in the crystals ttyr-248 interacts with the active site zinc atom (W.D. Lipscomb (1973), Proc. Nat. Acad. Sci U.S. 70, 3797). Thus, even in the crystals the enzyme exists in at least two different conformations. In one of these Tyr-248 is near while in the other it is far from the zinc atom. The spectral effects of Gly-L-Tyr and beta-phenylpropionate on solutions of arsanilazo- and of nitrocarboxypeptidase demonstrate that during the catalytic process Tyr-248 moves away from the zinc atom. This implies a mechanistic role for Tyr-248 different from that postulated on the basis of X-ray crystallographic analysis. Indeed, the proximity of ttyr-248 to the zinc atom, when altered by substrates and inhibitor, may reflect certain of the properties characteristic of the entatic, active site."}
{"id": "PMID:234738", "title": "Proton magnetic resonance studies of carbonic anhydrase. I. Identification of histidine resonances.", "content": "Nuclear magnetic resonance (nmr) spectra of human carbonic anhydrase B recorded in deuterium oxide reveal seven discrete single proton resonances between 7 and 9 ppm downfield from sodium 2,2-dimethyl-i-silapentane-5-sulfonate. Simplification of spectra by use of Fremy's salt, comparison of peak widths at intersections, and evaluation of the results of inhibition and modification experiments permit determination of the pH dependencies of these resonances. Five of these peaks change position with increasing pH; three move upfield by approximately 95 Hz and two move downfield by 10 and 23 Hz. The first three reflect residues with pK values of 7.23, 6.98, and 6 and can be assigned to the C-2 protons of histidines. The two remaining pH dependent resonances reflect groups with pK values of 8.2 and 8.24. Their line widths and T1 values are comparable to those of the first group, and they also appear to reflect C-H protons of histidines. Despite the structural and functional similarities of the B and C isozymes of human carbonic anhydrase, few of the low field resonances appear to be common to both. Six histidine C-2 protons are observed in the C enzyme and reflect groups with pK values of approximately 7.3, 6.5, 5.7, 6.6, 6.6, and 6.4. A seventh peak contains two protons and moves upfield with increasing pH without titrating. A final resonance to low field moves downfield with increasing pH and reflects a group with a pK between 6 and 7. Its behavior resembles that of peak 1 of the human B enzyme, and it also appears to be a histidine C-H proton. This peak may reflect a conserved residue in the two isozymes that plays an important role in enzymatic function, as discussed in the following paper.", "contents": "Proton magnetic resonance studies of carbonic anhydrase. I. Identification of histidine resonances. Nuclear magnetic resonance (nmr) spectra of human carbonic anhydrase B recorded in deuterium oxide reveal seven discrete single proton resonances between 7 and 9 ppm downfield from sodium 2,2-dimethyl-i-silapentane-5-sulfonate. Simplification of spectra by use of Fremy's salt, comparison of peak widths at intersections, and evaluation of the results of inhibition and modification experiments permit determination of the pH dependencies of these resonances. Five of these peaks change position with increasing pH; three move upfield by approximately 95 Hz and two move downfield by 10 and 23 Hz. The first three reflect residues with pK values of 7.23, 6.98, and 6 and can be assigned to the C-2 protons of histidines. The two remaining pH dependent resonances reflect groups with pK values of 8.2 and 8.24. Their line widths and T1 values are comparable to those of the first group, and they also appear to reflect C-H protons of histidines. Despite the structural and functional similarities of the B and C isozymes of human carbonic anhydrase, few of the low field resonances appear to be common to both. Six histidine C-2 protons are observed in the C enzyme and reflect groups with pK values of approximately 7.3, 6.5, 5.7, 6.6, 6.6, and 6.4. A seventh peak contains two protons and moves upfield with increasing pH without titrating. A final resonance to low field moves downfield with increasing pH and reflects a group with a pK between 6 and 7. Its behavior resembles that of peak 1 of the human B enzyme, and it also appears to be a histidine C-H proton. This peak may reflect a conserved residue in the two isozymes that plays an important role in enzymatic function, as discussed in the following paper."}
{"id": "PMID:234739", "title": "Proton magnetic resonance studies of carbonic anhydrase. II. Group controlling catalytic activity.", "content": "The seven resonances observed in the histidine region of the proton magnetic resonance (pmr) spectrum of human carbonic anhydrase B and reported in the preceding paper are studied in the presence of sulfonamide, azide, cyanide, and chloride inhibitors and in metal-free, cadmium substituted, cobalt substituted, and carboxymethylated forms of the enzyme. Results indicate that the two resonances that move-downfield with increasing pH and the two that do not move with pH reflect residues located at the active site. The first two resonances are assigned to the same titratable histidine whose pK value of 8.24 corresponds to that of the group controlling catalytic activity. Addition of anions or sulfonamides, removal of zinc, or substitution of cadmium for zinc at the active site, procedures known to abolish enzymatic activity, prevent titration of this residue. Partial inhibition of carbonic anhydrase by chloride slectively increases the pK value of the group controlling catalytic activity and of the histidine with pK equals 8.24. Experiments with metal-free and cadmium carbonic anhydrases and comparisons with model systems suggest that this histidine is bound to the metal ion at high pH; at low pH this complex appears to dissociate as protons compete with the metal for the imidazole group. It is proposed that ionization of the group controlling catalytic activity represents loss of the pyrrole proton of this neutral ligand when it binds to Zn(II), forming an imidazolate anion and juxtaposing a strong base and a powerful Lewis acid at the active site. When bound to zinc as an anion, this histidine can act as a general base catalyst in the hydration of carbon dioxide and be replaced as a metal ligand by an oxygen of the substrate in the course of the reaction. The histidine-metal complex is thought to exist in a strained configuration in the active enzyme so that its imidazole-metal bond is readily broken on addition of substrates or inhibitors. This model is consistent with the available data on the enzyme and is discussed in relation to alternative proposals.", "contents": "Proton magnetic resonance studies of carbonic anhydrase. II. Group controlling catalytic activity. The seven resonances observed in the histidine region of the proton magnetic resonance (pmr) spectrum of human carbonic anhydrase B and reported in the preceding paper are studied in the presence of sulfonamide, azide, cyanide, and chloride inhibitors and in metal-free, cadmium substituted, cobalt substituted, and carboxymethylated forms of the enzyme. Results indicate that the two resonances that move-downfield with increasing pH and the two that do not move with pH reflect residues located at the active site. The first two resonances are assigned to the same titratable histidine whose pK value of 8.24 corresponds to that of the group controlling catalytic activity. Addition of anions or sulfonamides, removal of zinc, or substitution of cadmium for zinc at the active site, procedures known to abolish enzymatic activity, prevent titration of this residue. Partial inhibition of carbonic anhydrase by chloride slectively increases the pK value of the group controlling catalytic activity and of the histidine with pK equals 8.24. Experiments with metal-free and cadmium carbonic anhydrases and comparisons with model systems suggest that this histidine is bound to the metal ion at high pH; at low pH this complex appears to dissociate as protons compete with the metal for the imidazole group. It is proposed that ionization of the group controlling catalytic activity represents loss of the pyrrole proton of this neutral ligand when it binds to Zn(II), forming an imidazolate anion and juxtaposing a strong base and a powerful Lewis acid at the active site. When bound to zinc as an anion, this histidine can act as a general base catalyst in the hydration of carbon dioxide and be replaced as a metal ligand by an oxygen of the substrate in the course of the reaction. The histidine-metal complex is thought to exist in a strained configuration in the active enzyme so that its imidazole-metal bond is readily broken on addition of substrates or inhibitors. This model is consistent with the available data on the enzyme and is discussed in relation to alternative proposals."}
{"id": "PMID:234740", "title": "Proton magnetic resonance studies of carbonic anhydrase. III. Binding of sulfonamides.", "content": "Resonances of the histidine region of human carbonic anhydrase B have been studied by proton magnetic resonance spectroscopy in the presence of seven sulfonamide inhibitors. Results of difference spectroscopy and observation of the C-2 resonance of an additional titratable histidine in some of these spectra suggest a conformational change in the enzyme, while the large number of unaltered resonances indicates involvement of only a few residues. Inhibition of carbonic anhydrase by sulfonamides appears to involve: stabilization of an appropriately oriented initial complex by hydrophobic binding of the aromatic ring of the inhibitor to residues of the cavity forming the active site; ionization of the sulfonamido group, facilitated by its proximity to zinc; protonation and displacement of the high pH ligand to the metal controlling catalytic activity, thought here to be a histidine residue; and formation by the sulfonamido group of an ionic bond to zinc and a hydrogen bond to the hydroxyl group of serine or threonine. Diversity of spectra produced with various sulfonamides suggests that substituents on the ring and heteroatoms within the ring interact with additional groups at the active site. Increase in inhibitory potency appears to involve optimizing the number as well as the strength of these interactions. An upper limit for the dissociation rate of these complexes of 10 sec-1 was obtained.", "contents": "Proton magnetic resonance studies of carbonic anhydrase. III. Binding of sulfonamides. Resonances of the histidine region of human carbonic anhydrase B have been studied by proton magnetic resonance spectroscopy in the presence of seven sulfonamide inhibitors. Results of difference spectroscopy and observation of the C-2 resonance of an additional titratable histidine in some of these spectra suggest a conformational change in the enzyme, while the large number of unaltered resonances indicates involvement of only a few residues. Inhibition of carbonic anhydrase by sulfonamides appears to involve: stabilization of an appropriately oriented initial complex by hydrophobic binding of the aromatic ring of the inhibitor to residues of the cavity forming the active site; ionization of the sulfonamido group, facilitated by its proximity to zinc; protonation and displacement of the high pH ligand to the metal controlling catalytic activity, thought here to be a histidine residue; and formation by the sulfonamido group of an ionic bond to zinc and a hydrogen bond to the hydroxyl group of serine or threonine. Diversity of spectra produced with various sulfonamides suggests that substituents on the ring and heteroatoms within the ring interact with additional groups at the active site. Increase in inhibitory potency appears to involve optimizing the number as well as the strength of these interactions. An upper limit for the dissociation rate of these complexes of 10 sec-1 was obtained."}
{"id": "PMID:234741", "title": "Nicotinamide 3,N4-ethenocytosine dinucleotide, an analog of nicotinamide adenine dinucleotide. Synthesis and enzyme studies.", "content": "A structural analog of NAD+, NICOTINAMIDE 3,N-4ethenocytosine dinucleotide (epsilonNCD+), has been synthesized, characterized, and compared in activity with the natural coenzyme in several enzyme systems. The Vmax and apparent Km values were determined for NAD+, epsilonNCD+, and epsilonNAD+ (nicotinamide 1, N6-ethenoadenine dinucleotide) with yeast alcohol, horse liver alcohol, pig heart malate, beef liver glutamate, and rabbit muscle lactate and glyceraldehyde-3-phosphate dehydrogenases. The Vmax for epsilonNCD+ was as great or greater than that obtained for NAD+ with three of the enzymes, 60-80 per cent with two others, and 14 percent with one. EpsilonNCD+ was found to be more active than epsilonNAD+ with all six dehydrogenases. EpsilonNCD+ served as a substrate for Neurospora crassa tnadase, but could not be phosphorylated with pigeon liver NAD+ kinase. NAD+ pyrophosphorylase from pig liver was unable to catalyze the formation of epsilonNCD+ from the triphosphate derivative of epsilon-cytidine and nicotinamide mononucleotide, but was able to slowly catalyze the pyrolytic cleavage of epsilonNCD+. The coenzyme activity of epsilonNCD+ with dehydrogenases can be discussed in terms of the close spatial homology of epsilonNCD+ and NAD+, which may allow similar accommodations within the enzyme binding regions.", "contents": "Nicotinamide 3,N4-ethenocytosine dinucleotide, an analog of nicotinamide adenine dinucleotide. Synthesis and enzyme studies. A structural analog of NAD+, NICOTINAMIDE 3,N-4ethenocytosine dinucleotide (epsilonNCD+), has been synthesized, characterized, and compared in activity with the natural coenzyme in several enzyme systems. The Vmax and apparent Km values were determined for NAD+, epsilonNCD+, and epsilonNAD+ (nicotinamide 1, N6-ethenoadenine dinucleotide) with yeast alcohol, horse liver alcohol, pig heart malate, beef liver glutamate, and rabbit muscle lactate and glyceraldehyde-3-phosphate dehydrogenases. The Vmax for epsilonNCD+ was as great or greater than that obtained for NAD+ with three of the enzymes, 60-80 per cent with two others, and 14 percent with one. EpsilonNCD+ was found to be more active than epsilonNAD+ with all six dehydrogenases. EpsilonNCD+ served as a substrate for Neurospora crassa tnadase, but could not be phosphorylated with pigeon liver NAD+ kinase. NAD+ pyrophosphorylase from pig liver was unable to catalyze the formation of epsilonNCD+ from the triphosphate derivative of epsilon-cytidine and nicotinamide mononucleotide, but was able to slowly catalyze the pyrolytic cleavage of epsilonNCD+. The coenzyme activity of epsilonNCD+ with dehydrogenases can be discussed in terms of the close spatial homology of epsilonNCD+ and NAD+, which may allow similar accommodations within the enzyme binding regions."}
{"id": "PMID:234742", "title": "Human pancreatic enzymes: purification and characterization of a nonelastolytic enzyme, protease E. resembling elastase.", "content": "?An enzyme with proteolytic activity has been isolated from activated extracts of human pancreatic tissue. The purification procedure included salt fractionation followed by ion-exchange chromatography on SE-TSephadex C-25 and on DEAE-Sephadex A-50. The homogeneity of this enzyme, designated protease te, was demonstrated by disc electrophoresis and by sedimentation equilibrium centrifugation stidues. The homogeneous enzyme shows the ability to hydrolyze many of the conventional synthetic substrates used for the identification of elastase activity; however, it demonstrates no significant elastolytic activity. A comparison of human protease E with porcine elastase reveals a high degree of similarity between the two proteases with respect to inhibition by active-site directed peptide chloromethyl ketones, stability, decreased susceptibility to naturally occurring proteinase inhibitors, and specificity for synthetic substrates as well as several other physical properties. The major difference between human protease E and porcine elastase, other than the lack of elastolytic activity by human protease E, seems to be in the ionic character and the amino acid composition of these two proteins. Porcine elastase is a cationic enzyme, while human protease E appears to be anionic in nature. These dissimilarities concerning elastolytic activity and ionic character appear to be directly related.", "contents": "Human pancreatic enzymes: purification and characterization of a nonelastolytic enzyme, protease E. resembling elastase. ?An enzyme with proteolytic activity has been isolated from activated extracts of human pancreatic tissue. The purification procedure included salt fractionation followed by ion-exchange chromatography on SE-TSephadex C-25 and on DEAE-Sephadex A-50. The homogeneity of this enzyme, designated protease te, was demonstrated by disc electrophoresis and by sedimentation equilibrium centrifugation stidues. The homogeneous enzyme shows the ability to hydrolyze many of the conventional synthetic substrates used for the identification of elastase activity; however, it demonstrates no significant elastolytic activity. A comparison of human protease E with porcine elastase reveals a high degree of similarity between the two proteases with respect to inhibition by active-site directed peptide chloromethyl ketones, stability, decreased susceptibility to naturally occurring proteinase inhibitors, and specificity for synthetic substrates as well as several other physical properties. The major difference between human protease E and porcine elastase, other than the lack of elastolytic activity by human protease E, seems to be in the ionic character and the amino acid composition of these two proteins. Porcine elastase is a cationic enzyme, while human protease E appears to be anionic in nature. These dissimilarities concerning elastolytic activity and ionic character appear to be directly related."}
{"id": "PMID:234743", "title": "The solution conformation of nicotinamide mononucleotide: a quantitative application of the nuclear Overhauser effect.", "content": "Torsion about the glycosidic linkage in nicotinamide mononucleotide has been investigated by quantitative application of the nuclear Overhauser effect. These measurements show that the syn (chi congruent to 20 degrees) and anti (chi congruent to 200 degrees) conformers of the title compound are isoenergetic, or nearly so, and interconverting rapidly. The syn/anti partition is not measurably affected by either changes in pH or temperature.", "contents": "The solution conformation of nicotinamide mononucleotide: a quantitative application of the nuclear Overhauser effect. Torsion about the glycosidic linkage in nicotinamide mononucleotide has been investigated by quantitative application of the nuclear Overhauser effect. These measurements show that the syn (chi congruent to 20 degrees) and anti (chi congruent to 200 degrees) conformers of the title compound are isoenergetic, or nearly so, and interconverting rapidly. The syn/anti partition is not measurably affected by either changes in pH or temperature."}
{"id": "PMID:234744", "title": "Partial characterization of the cytosol 3 alpha-hydroxysteroid: NAD(P)+oxidoreductase of rat ventral prostate.", "content": "The cytosol 3alpha-hydroxysteroid dehydrogenase of rat ventral prostate has been partially purified. The rates of both the oxidation and reduction by crude and partially purified enzymes have been measured with a variety of radioactive substrates, and the effects of several inhibitor steroids have been assessed. Four conclusions have been drawn from the study. First, no detectable 3beta-androstanediol was formed from dihydrotestosterone, and the oxidation of 3beta-androstanediol was undetectable. Second, the cytosol enzyme exhibits a distinct and unique substrate specificity in that steroids with keto or hydroxyl substitution on the 11th carbon of the steroid cannot serve as substrates or as inhibitors of the enzyme. Third, either 5alpha or 5 beta reduction of delta4,3-keto steroids must take place before the steroids can serve as substrates of the enzyme. Fourth, many delta4,3-keto steroids that cannot act as substrates for the enzyme inhibit the enzyme competitively and may well serve as physiological regulators of the reaction in intact cell.", "contents": "Partial characterization of the cytosol 3 alpha-hydroxysteroid: NAD(P)+oxidoreductase of rat ventral prostate. The cytosol 3alpha-hydroxysteroid dehydrogenase of rat ventral prostate has been partially purified. The rates of both the oxidation and reduction by crude and partially purified enzymes have been measured with a variety of radioactive substrates, and the effects of several inhibitor steroids have been assessed. Four conclusions have been drawn from the study. First, no detectable 3beta-androstanediol was formed from dihydrotestosterone, and the oxidation of 3beta-androstanediol was undetectable. Second, the cytosol enzyme exhibits a distinct and unique substrate specificity in that steroids with keto or hydroxyl substitution on the 11th carbon of the steroid cannot serve as substrates or as inhibitors of the enzyme. Third, either 5alpha or 5 beta reduction of delta4,3-keto steroids must take place before the steroids can serve as substrates of the enzyme. Fourth, many delta4,3-keto steroids that cannot act as substrates for the enzyme inhibit the enzyme competitively and may well serve as physiological regulators of the reaction in intact cell."}
{"id": "PMID:234745", "title": "Membrane properties of Thermoplasma acidophila.", "content": "Plasma membranes were isolated from Thermoplasma acidophila, a mycoplasma-like organism which grows optimally at pH 2 and 59 degrees. Cells in concentrated suspensions were lysed by titrating to pH 9.3. The membranes were purified by washing at pH 10 and centrifuging in a discontinuous sucrose gradient. Membrane purity was assessed by electron microscopy, determination of deoxyribonucleic acid content, polyacrylamide gel electrophoretic behavior. Gel patterns and amino acid composition of cells and membranes were found to differ significantly. The lipid contained small amounts of fatty acid esters and larger amounts of branched long-chain alkyl ethers.", "contents": "Membrane properties of Thermoplasma acidophila. Plasma membranes were isolated from Thermoplasma acidophila, a mycoplasma-like organism which grows optimally at pH 2 and 59 degrees. Cells in concentrated suspensions were lysed by titrating to pH 9.3. The membranes were purified by washing at pH 10 and centrifuging in a discontinuous sucrose gradient. Membrane purity was assessed by electron microscopy, determination of deoxyribonucleic acid content, polyacrylamide gel electrophoretic behavior. Gel patterns and amino acid composition of cells and membranes were found to differ significantly. The lipid contained small amounts of fatty acid esters and larger amounts of branched long-chain alkyl ethers."}
{"id": "PMID:234746", "title": "Mutants of Escherichia coli K12 unable to grow on non-fermentable carbon substrates.", "content": "Among a number of mutants unable to utilize non-fermentable carbon substrates, scoring for membrane ATPase and for ATP-driven transhydrogenase activity permitted to distinguish two phenotypes: (A) mutants lacking ATPase and ATP-driven transhydrogenase; (B) one mutant with an ATPase which behaved according to several criteria as released into solution instead of being membrane bound, a.o it exhibited no ATP-driven transhydrogenase activity. All A and B mutants exhibited a common nutritional pattern. The ATPase-deficient group, when scored for ATPase-binding sites on its membrane particles revealed three different subgroups: (1) mutants having free ATPase-binding sites, (2) mutants with ATPase-binding sites made available by the procedure which releases ATPase from wild-type membrane, and (3) mutants with no detectable ATPase-binding sites. Membranes of the mutant B with unbound ATPase also exhibited a deficiency in ATPase-binding sites, but its soluble ATPase was also found unable to bind to ATPase-binding sites of wild type membranes. The double alteration, namely abnormal or inactive ATPase and absence of ATPase-binding sites on the membrane is compatible with a single mutational defect.", "contents": "Mutants of Escherichia coli K12 unable to grow on non-fermentable carbon substrates. Among a number of mutants unable to utilize non-fermentable carbon substrates, scoring for membrane ATPase and for ATP-driven transhydrogenase activity permitted to distinguish two phenotypes: (A) mutants lacking ATPase and ATP-driven transhydrogenase; (B) one mutant with an ATPase which behaved according to several criteria as released into solution instead of being membrane bound, a.o it exhibited no ATP-driven transhydrogenase activity. All A and B mutants exhibited a common nutritional pattern. The ATPase-deficient group, when scored for ATPase-binding sites on its membrane particles revealed three different subgroups: (1) mutants having free ATPase-binding sites, (2) mutants with ATPase-binding sites made available by the procedure which releases ATPase from wild-type membrane, and (3) mutants with no detectable ATPase-binding sites. Membranes of the mutant B with unbound ATPase also exhibited a deficiency in ATPase-binding sites, but its soluble ATPase was also found unable to bind to ATPase-binding sites of wild type membranes. The double alteration, namely abnormal or inactive ATPase and absence of ATPase-binding sites on the membrane is compatible with a single mutational defect."}
{"id": "PMID:234747", "title": "Variations in the pathways of malate oxidation and phosphorylation in different species of Mycobacteria.", "content": "Mycobacterium tuberculosis H37Rv, the slow-growing human pathogenic strain of tubercle bacilli and Mycobacterium smegmatis and Mycobacterium phlei, the fast-growing saprophytes, have shown variations regarding the type of dehydrogenase that initiates malate oxidation in the respiratory chain. M. tuberculosis H37Rv is characterized by having a malate oxidase system (designated MALNAD pathway) in which malate oxidation is mediated by the NAD+-dependent malate dehydrogenase (EC 1.1.1.37) but not by FAD-dependent malate-vitamin K reductase. M. smegmatis possesses a different malate oxidase system (designated MALFAD pathway) in which malate oxidation is exclusively carried out by the FAD-dependent malate-vitamin K reductase because NAD+-dependent malate dehydrogenase is absent in this organism. M. phlei has a mixed system of malate oxidase (designated MALNAD+FAD pathways) in which both the NAD+-and FAD-dependent dehydrogenases take part. In all the three systems, the rest of the electron transport chain is common.", "contents": "Variations in the pathways of malate oxidation and phosphorylation in different species of Mycobacteria. Mycobacterium tuberculosis H37Rv, the slow-growing human pathogenic strain of tubercle bacilli and Mycobacterium smegmatis and Mycobacterium phlei, the fast-growing saprophytes, have shown variations regarding the type of dehydrogenase that initiates malate oxidation in the respiratory chain. M. tuberculosis H37Rv is characterized by having a malate oxidase system (designated MALNAD pathway) in which malate oxidation is mediated by the NAD+-dependent malate dehydrogenase (EC 1.1.1.37) but not by FAD-dependent malate-vitamin K reductase. M. smegmatis possesses a different malate oxidase system (designated MALFAD pathway) in which malate oxidation is exclusively carried out by the FAD-dependent malate-vitamin K reductase because NAD+-dependent malate dehydrogenase is absent in this organism. M. phlei has a mixed system of malate oxidase (designated MALNAD+FAD pathways) in which both the NAD+-and FAD-dependent dehydrogenases take part. In all the three systems, the rest of the electron transport chain is common."}
{"id": "PMID:234748", "title": "Control of proton translocation induced by ATPase activity in chloroplasts.", "content": "1. Proton uptake was induced by ATP in the dark following light triggering of ATPase activity in chloroplasts. The accumulated protons were released when ATPase activity was inhibited by the energy transfer inhibitor DIO-9. 2. Approximately two protons were taken up for each ATP hydrolyzed at pH 8. A drop in H+/ATP ratio was caused by uncouplers such as NH4Cl and carbonyl cyanide p-trifluoromethoxyphenylhydrazone. These uncouplers caused an increase in the rate of ATP hydrolysis without a corresponding increase in proton uptake. 3. The energy transfer inhibitor dicyclocarbodiimide inhibited both ATPase activity and the rate of proton uptake without changing the H+/ATP ratio. 4. The antibiotic valinomycin caused an increase in the rate of both proton uptake and ATP hydrolysis without altering the ratio of H+/ATP. The H+/ATP ratio varied with changes in the external pH. The results were discussed in view of the chemiosmotic theory of oxidative and photosynthetic phosphorylation.", "contents": "Control of proton translocation induced by ATPase activity in chloroplasts. 1. Proton uptake was induced by ATP in the dark following light triggering of ATPase activity in chloroplasts. The accumulated protons were released when ATPase activity was inhibited by the energy transfer inhibitor DIO-9. 2. Approximately two protons were taken up for each ATP hydrolyzed at pH 8. A drop in H+/ATP ratio was caused by uncouplers such as NH4Cl and carbonyl cyanide p-trifluoromethoxyphenylhydrazone. These uncouplers caused an increase in the rate of ATP hydrolysis without a corresponding increase in proton uptake. 3. The energy transfer inhibitor dicyclocarbodiimide inhibited both ATPase activity and the rate of proton uptake without changing the H+/ATP ratio. 4. The antibiotic valinomycin caused an increase in the rate of both proton uptake and ATP hydrolysis without altering the ratio of H+/ATP. The H+/ATP ratio varied with changes in the external pH. The results were discussed in view of the chemiosmotic theory of oxidative and photosynthetic phosphorylation."}
{"id": "PMID:234749", "title": "The mechanism of reduction of cytochrome c as studied by pulse radiolysis.", "content": "1. The reaction of hydrated electrons with ferricytochrome c was studied using the pulse-radiolysis technique. 2. In 3.3 mM phosphate-buffer (pH 7.2), 100 mM methanol and at a concentration of cytochrome c of less than 20 muM the reduction kinetics of ferricytochrome c by hydrated electrons is a bimolecular process with a rate constant of 4.5-10-10 M-1-S-1 (21 degrees C). 3. At a concentration of cytochrome c of more than 20 muM the apparent order of the reaction of hydrated electrons with ferricytochrome c measured at 650 nm decreases due to the occurrence of a rate-determining first-order process with an estimated rate constant of 5-10-6s-1 (pH 7.2, 21 degrees C). 4. At high concentration of cytochrome c the reaction-time courses measured at 580 and 695 nm appear to be biphasic. A rapid initial phase (75% and 30% of total absorbance change at 580 and 695 nm, respectively), corresponding to the reduction reaction, is followed by a first-order change in absorbance with a rate constant of 1.3-10-5 S-1 (pH 7.2, 21 degrees C). 5. The results are interpreted in a scheme in which first a transient complex between cytochrome c and the hydrated electron is formed, after which the heme iron is reduced and followed by relaxation of the protein from its oxidized to its reduced conformation. 6. It is calculated that one of each three encounters of the hydrated electron and ferricytochrome c results in a reduction of the heme iron. This high reaction probability is discussed in terms of charge and solvent interactions. 7. A reduction mechanism for cytochrome c is favored in which the reduction equivalent from the hydrated electron is transmitted through a specific pathway from the surface of the molecule to the heme iron.", "contents": "The mechanism of reduction of cytochrome c as studied by pulse radiolysis. 1. The reaction of hydrated electrons with ferricytochrome c was studied using the pulse-radiolysis technique. 2. In 3.3 mM phosphate-buffer (pH 7.2), 100 mM methanol and at a concentration of cytochrome c of less than 20 muM the reduction kinetics of ferricytochrome c by hydrated electrons is a bimolecular process with a rate constant of 4.5-10-10 M-1-S-1 (21 degrees C). 3. At a concentration of cytochrome c of more than 20 muM the apparent order of the reaction of hydrated electrons with ferricytochrome c measured at 650 nm decreases due to the occurrence of a rate-determining first-order process with an estimated rate constant of 5-10-6s-1 (pH 7.2, 21 degrees C). 4. At high concentration of cytochrome c the reaction-time courses measured at 580 and 695 nm appear to be biphasic. A rapid initial phase (75% and 30% of total absorbance change at 580 and 695 nm, respectively), corresponding to the reduction reaction, is followed by a first-order change in absorbance with a rate constant of 1.3-10-5 S-1 (pH 7.2, 21 degrees C). 5. The results are interpreted in a scheme in which first a transient complex between cytochrome c and the hydrated electron is formed, after which the heme iron is reduced and followed by relaxation of the protein from its oxidized to its reduced conformation. 6. It is calculated that one of each three encounters of the hydrated electron and ferricytochrome c results in a reduction of the heme iron. This high reaction probability is discussed in terms of charge and solvent interactions. 7. A reduction mechanism for cytochrome c is favored in which the reduction equivalent from the hydrated electron is transmitted through a specific pathway from the surface of the molecule to the heme iron."}
{"id": "PMID:234750", "title": "Electric birefringence of myosin subfragments.", "content": "Electric birefringence measurements have been made on aqueous solutions of myosin subfragments, heavy meromyosin, subfragments 1 and 2 (S-1 and S-2). All of these showed positive electric birefringence. Heavy meromyosin and S-2 showed a large intrinsic Kerr constant. From the analysis of the build up and decay process of the birefringence, the contribution of the slow induced dipole moment was concluded in heavy meromyosin and S-2, although the existence of the permanent dipole moment was not completely excluded. The decay process of the birefringence of heavy meromyosin was found to consist of two components; the fast one of which had a relaxation time of the same order as that of S-1. This is probably due to the presence of a flexible hinge in heavy meromyosin.", "contents": "Electric birefringence of myosin subfragments. Electric birefringence measurements have been made on aqueous solutions of myosin subfragments, heavy meromyosin, subfragments 1 and 2 (S-1 and S-2). All of these showed positive electric birefringence. Heavy meromyosin and S-2 showed a large intrinsic Kerr constant. From the analysis of the build up and decay process of the birefringence, the contribution of the slow induced dipole moment was concluded in heavy meromyosin and S-2, although the existence of the permanent dipole moment was not completely excluded. The decay process of the birefringence of heavy meromyosin was found to consist of two components; the fast one of which had a relaxation time of the same order as that of S-1. This is probably due to the presence of a flexible hinge in heavy meromyosin."}
{"id": "PMID:234751", "title": "Heavy metal-nucleotide interactions. III. The participation of amino groups in the binding of methylmercury (II) to cytidine and adenosine 5'-phosphate in aqueous solution: studies by Raman difference spectrophotometry.", "content": "Raman difference spectrophotometry has been used to study the interaction of CH3Hg(II) with cytidine and Ado-5'-P at high pH. In contrast to the binding reactions which occur at lower pH or in non-aqueous solvents such as dimethyl sulfoxide, a proton is transferred from the amino group; and the complexes are CH3HgCydH-1 and CH3HgAdoH-1-5'-P. The spectra are significantly different from those of the cationic complexes. The integrated intensities of ligand modes which shift upon metalation can be used to measure the concentration of unreacted ligand and consequently the extent of the reaction. Equilibrium constants for the reactions CH3HgOH + L yields CH3HgLH-1 + H2O were estimated to be log KCyd equals 0.63 plus or minus 0.05 and log KAdo-5'-P equals 0.85 plus or minus 0.05, in fair agreement with values determined under very different conditions by ultraviolet spectrophotometry. The vibrational spectrum of the ligand in CH3HgCydH-1 is virtually the same as that of UrdH-1- which is isoelectronic. The spectrum of the ligand in CH3HgAdoH-1-5'-P is more similar to the isoelectronic base InoH-1-than to Ado-5'-P, although the resemblance is not so close as in the CydH-1---UrdH-1-case. The structures of these complexes are discussed on the basis of their vibrational spectra and similarities in the spectra of related compounds. It is concluded that the CH3Hg(II) binds to the amino nitrogen at high pH with both cytidine and Ado-5'-P. In neutral solution with excess CH3Hg(II), metalation occurs on the amino groups, on the ring, and also on the ribose.", "contents": "Heavy metal-nucleotide interactions. III. The participation of amino groups in the binding of methylmercury (II) to cytidine and adenosine 5'-phosphate in aqueous solution: studies by Raman difference spectrophotometry. Raman difference spectrophotometry has been used to study the interaction of CH3Hg(II) with cytidine and Ado-5'-P at high pH. In contrast to the binding reactions which occur at lower pH or in non-aqueous solvents such as dimethyl sulfoxide, a proton is transferred from the amino group; and the complexes are CH3HgCydH-1 and CH3HgAdoH-1-5'-P. The spectra are significantly different from those of the cationic complexes. The integrated intensities of ligand modes which shift upon metalation can be used to measure the concentration of unreacted ligand and consequently the extent of the reaction. Equilibrium constants for the reactions CH3HgOH + L yields CH3HgLH-1 + H2O were estimated to be log KCyd equals 0.63 plus or minus 0.05 and log KAdo-5'-P equals 0.85 plus or minus 0.05, in fair agreement with values determined under very different conditions by ultraviolet spectrophotometry. The vibrational spectrum of the ligand in CH3HgCydH-1 is virtually the same as that of UrdH-1- which is isoelectronic. The spectrum of the ligand in CH3HgAdoH-1-5'-P is more similar to the isoelectronic base InoH-1-than to Ado-5'-P, although the resemblance is not so close as in the CydH-1---UrdH-1-case. The structures of these complexes are discussed on the basis of their vibrational spectra and similarities in the spectra of related compounds. It is concluded that the CH3Hg(II) binds to the amino nitrogen at high pH with both cytidine and Ado-5'-P. In neutral solution with excess CH3Hg(II), metalation occurs on the amino groups, on the ring, and also on the ribose."}
{"id": "PMID:234752", "title": "Cytoplasmic origin of the so-called nuclear neutral histone protease.", "content": "1. We have investigated the origin of proteolytic activity which causes degradation of histones in chromatin isolated from Xenopus liver and the rat liver at neutral pH. Polyacrylamide disc gel electrophoresis was used for detection of proteolytic products of histones. 2. No proteolytic degradation of histones occurs in chromatin isolated from Xenopus erythrocytes and rat liver according to our procedure even after prolonged incubation at pH 8.0 and pH 5.0. However with chromatin isolated from Xenopus liver a high level of histone degradation is observed under similar conditions. 3. Mixing isolated nuclei from Xenopus erythrocytes with a crude cytoplasmic fraction from Xenopus liver causes histone proteolysis in isolated chromatin at pH 8.0. In similar experiments with corresponding fractions from rat liver histone proteolysis can be introduced only after repeated freezing and thawing of the cytoplasmic fraction. 4. A purified lysosomal preparation from rat liver causes a similar type of histone degradation upon incubation with chromatin from Xenopus erythrocytes and rat liver. 5. The neutral proteolytic activity that can be introduced in isolated chromatin by a crude cytoplasmic fraction and by a purified lysosomal erythrocytes and rat liver. 5. The neutral proteolytic activity that can be introduced in isolated chromatin by a crude cytoplasmic fraction and by a purified lysosomal fraction from rat liver is inhibited by sodium bisulphite. 6. We conclude that the neutral proteolytic activity which causes degradation of histones in isolated chromatin is due to a contamination with neutral protease(s) originating from cytoplasmic organelles.", "contents": "Cytoplasmic origin of the so-called nuclear neutral histone protease. 1. We have investigated the origin of proteolytic activity which causes degradation of histones in chromatin isolated from Xenopus liver and the rat liver at neutral pH. Polyacrylamide disc gel electrophoresis was used for detection of proteolytic products of histones. 2. No proteolytic degradation of histones occurs in chromatin isolated from Xenopus erythrocytes and rat liver according to our procedure even after prolonged incubation at pH 8.0 and pH 5.0. However with chromatin isolated from Xenopus liver a high level of histone degradation is observed under similar conditions. 3. Mixing isolated nuclei from Xenopus erythrocytes with a crude cytoplasmic fraction from Xenopus liver causes histone proteolysis in isolated chromatin at pH 8.0. In similar experiments with corresponding fractions from rat liver histone proteolysis can be introduced only after repeated freezing and thawing of the cytoplasmic fraction. 4. A purified lysosomal preparation from rat liver causes a similar type of histone degradation upon incubation with chromatin from Xenopus erythrocytes and rat liver. 5. The neutral proteolytic activity that can be introduced in isolated chromatin by a crude cytoplasmic fraction and by a purified lysosomal erythrocytes and rat liver. 5. The neutral proteolytic activity that can be introduced in isolated chromatin by a crude cytoplasmic fraction and by a purified lysosomal fraction from rat liver is inhibited by sodium bisulphite. 6. We conclude that the neutral proteolytic activity which causes degradation of histones in isolated chromatin is due to a contamination with neutral protease(s) originating from cytoplasmic organelles."}
{"id": "PMID:234753", "title": "Hydrogen-ion titration curve of ovomucoid.", "content": "A systematic study of the H+ titration curve of purified ovomucoid was made at three temperatures (15, 25 and 35 degrees C) and three ionic strengths (0.05, 0.15 and 1.0). In all, 49 protons were dissociated reversibly in the pH range, 2.0-12.0. From the analysis of the results up to pH 12.0, the numbers of different dissociable groups per 28 300 g protein, together with their intrinsic pK values in parentheses were found tp be' 27 sode-chain carboxyl (pKint=4.0), four imidazole (pKint=6.5), one alpha-amino (pKint=7.5), 12 epsilon-amino (pKint=9.6), one guanidino (pKint=11.8) and one alpha-carboxyl group with abnormally low pK. The total number of basic nitrogens per mole of the protein was 22 so that four guanidino groups remained untitrated up to pH 12.0. Spectrophotometric titration showed that three out of five phenolic groups were titrated reversibly up to pH 11.9 with an intrinsic pK of 10.25; the remaining two groups became accessible only on protein denaturation. Viscosity results suggested absence of conformational change in the pH range 2.0-11.2. This explains the constancy of the pK values of carboxyl groups in the pH range 2.0-5.0. The empirical value of the electrostatic interaction factor, w, was 0.04, both in the carboxyl and phenolic regions.", "contents": "Hydrogen-ion titration curve of ovomucoid. A systematic study of the H+ titration curve of purified ovomucoid was made at three temperatures (15, 25 and 35 degrees C) and three ionic strengths (0.05, 0.15 and 1.0). In all, 49 protons were dissociated reversibly in the pH range, 2.0-12.0. From the analysis of the results up to pH 12.0, the numbers of different dissociable groups per 28 300 g protein, together with their intrinsic pK values in parentheses were found tp be' 27 sode-chain carboxyl (pKint=4.0), four imidazole (pKint=6.5), one alpha-amino (pKint=7.5), 12 epsilon-amino (pKint=9.6), one guanidino (pKint=11.8) and one alpha-carboxyl group with abnormally low pK. The total number of basic nitrogens per mole of the protein was 22 so that four guanidino groups remained untitrated up to pH 12.0. Spectrophotometric titration showed that three out of five phenolic groups were titrated reversibly up to pH 11.9 with an intrinsic pK of 10.25; the remaining two groups became accessible only on protein denaturation. Viscosity results suggested absence of conformational change in the pH range 2.0-11.2. This explains the constancy of the pK values of carboxyl groups in the pH range 2.0-5.0. The empirical value of the electrostatic interaction factor, w, was 0.04, both in the carboxyl and phenolic regions."}
{"id": "PMID:234754", "title": "Thyroid microsomal membrane proteins. Effects of solubilization on molecular size.", "content": "The molecular size of microsomal membrane proteins from frozen porcine thyroids before and after solubilization by proteolytic and non-proteolytic techniques has been investigated by means of polyacrylamide-gel electrophoresis in the presence of 1% sodium dodecylsulfate. When thyroid microsomal membrane proteins are solubilized by non-proteolytic methods such as high pH, n-butanol, or deoxycholate, no major change in the electrophoretic pattern compared to untreated microsomes has been observed, thereby suggesting that these non-proteolytic methods are capable of extracting membrane proteins from thyroid microsomes without altering their molecular size. However, treatment of microsomes with protein-solubilizing levels of trypsin (1-5 mug trypsin per mg thyroid protein) results in degradation of all major proteins with a molecular weight greater than 30 000. The high-molecular-weight proteins are particularly susceptible to attack by trypsin. Thus, these experiments indicate that the use of trypsin to solubilize thyroid microsomal membrane proteins, particularly thyroid peroxidase, will result in fragmented proteins and should be avoided if intact membrane proteins are desired.", "contents": "Thyroid microsomal membrane proteins. Effects of solubilization on molecular size. The molecular size of microsomal membrane proteins from frozen porcine thyroids before and after solubilization by proteolytic and non-proteolytic techniques has been investigated by means of polyacrylamide-gel electrophoresis in the presence of 1% sodium dodecylsulfate. When thyroid microsomal membrane proteins are solubilized by non-proteolytic methods such as high pH, n-butanol, or deoxycholate, no major change in the electrophoretic pattern compared to untreated microsomes has been observed, thereby suggesting that these non-proteolytic methods are capable of extracting membrane proteins from thyroid microsomes without altering their molecular size. However, treatment of microsomes with protein-solubilizing levels of trypsin (1-5 mug trypsin per mg thyroid protein) results in degradation of all major proteins with a molecular weight greater than 30 000. The high-molecular-weight proteins are particularly susceptible to attack by trypsin. Thus, these experiments indicate that the use of trypsin to solubilize thyroid microsomal membrane proteins, particularly thyroid peroxidase, will result in fragmented proteins and should be avoided if intact membrane proteins are desired."}
{"id": "PMID:234755", "title": "Isoelectric-focusing behavior of acid hydrolases in rat kidney lysosomes. Effects of the pH gradient, autolysis and neuraminidase.", "content": "Isoelectric focusing was used to study the multiple forms of acid phosphatase, arylsulfatase, beta-glucuronidase and beta-N-acetylhexosaminidase in lysosomes isolated from rat kidney. The isoelectric points of the main protein and hydrolase peaks were 1-1.5 units lower when electrofocusing was done in a pH 3-10 gradient than in a pH 10-3 gradient, apparently because the lysosomal constituents aggregated strongly at their isoelectric points and tended to settle somewhat in the gradient due to gravity. In the extended pH gradient the acidic form of each hydrolase occurred as asingle, relatively discrete peak. However, when pooled acidic fractions were refocused in a restricted pH gradient (pH 6-3 or 3-5) multiple acidic enzyme and protein components were resolved with isoelectric points between 2.7 and 5.1. When autolysis was minimized by extracting lysosomal fractions at alkaline pH (0.2% Triton X-100, 0.1%p-nitrophenyloxamic acid, 0.1 M glycine buffer, pH9) and including 0.1%p-NITROPHENYLOXAMIC ACID, AN INHIBITOR OF LYSOSOMAL NEURAMINIDASE AND CATHEPSIN D, in the pH gradient, arylsulfatase, beta-glucuronidase and beta-N-acetylhexosaminidase occurred in two forms, an acidic form with an isoelectric point of about 4.4, and a basic form with an  isoelectric point close to 6.2, 6.7 and 8.0, respectively. Acid phosphatase occurred in three forms with isoelectric points of 4.1, 5.6 and 7.4. When some autolytic digestion was permitted by extracting lysosomal fractions in an acidic medium (0.2% Triton X-100, 0.1 M sodium acetate buffer, pH 5.2) AT 0-4DEGREES C and omitting p-nitrophenyloxamic acid from the gradient, the acidic form of beta-glucuronidase and the intermediate form of acid phosphatase were lost, the isoelectric points of the acidic forms of acid phosphatase, arylsulfatase and beta-N-acetylhexosaminidase were increased 0.6-1.2 units, and the isoelectric point of the basic forms of acid phosphatase, arylsulfatase and beta-glucuronidase was increased 0.5 unit. When lysosomal extracts were incubated with bacterial neuraminidase before electrofocusing, the acidic forms of acid phosphatase, arylsulfatase and beta-glucuronidase were largely lost, the isoelectric point of the acidic form of beta-N-acetylhexosaminidase was increased from 4.5 to 6.4, and the isoelectric points of the basic forms of all four hydrolases were increased 0.5-1.5 units. Autoincubation of lysosomal extracts in vitro at pH 5.2 PRODUCED SIMILAR, THOUGH LESS MARKED, effects. cont'd", "contents": "Isoelectric-focusing behavior of acid hydrolases in rat kidney lysosomes. Effects of the pH gradient, autolysis and neuraminidase. Isoelectric focusing was used to study the multiple forms of acid phosphatase, arylsulfatase, beta-glucuronidase and beta-N-acetylhexosaminidase in lysosomes isolated from rat kidney. The isoelectric points of the main protein and hydrolase peaks were 1-1.5 units lower when electrofocusing was done in a pH 3-10 gradient than in a pH 10-3 gradient, apparently because the lysosomal constituents aggregated strongly at their isoelectric points and tended to settle somewhat in the gradient due to gravity. In the extended pH gradient the acidic form of each hydrolase occurred as asingle, relatively discrete peak. However, when pooled acidic fractions were refocused in a restricted pH gradient (pH 6-3 or 3-5) multiple acidic enzyme and protein components were resolved with isoelectric points between 2.7 and 5.1. When autolysis was minimized by extracting lysosomal fractions at alkaline pH (0.2% Triton X-100, 0.1%p-nitrophenyloxamic acid, 0.1 M glycine buffer, pH9) and including 0.1%p-NITROPHENYLOXAMIC ACID, AN INHIBITOR OF LYSOSOMAL NEURAMINIDASE AND CATHEPSIN D, in the pH gradient, arylsulfatase, beta-glucuronidase and beta-N-acetylhexosaminidase occurred in two forms, an acidic form with an isoelectric point of about 4.4, and a basic form with an  isoelectric point close to 6.2, 6.7 and 8.0, respectively. Acid phosphatase occurred in three forms with isoelectric points of 4.1, 5.6 and 7.4. When some autolytic digestion was permitted by extracting lysosomal fractions in an acidic medium (0.2% Triton X-100, 0.1 M sodium acetate buffer, pH 5.2) AT 0-4DEGREES C and omitting p-nitrophenyloxamic acid from the gradient, the acidic form of beta-glucuronidase and the intermediate form of acid phosphatase were lost, the isoelectric points of the acidic forms of acid phosphatase, arylsulfatase and beta-N-acetylhexosaminidase were increased 0.6-1.2 units, and the isoelectric point of the basic forms of acid phosphatase, arylsulfatase and beta-glucuronidase was increased 0.5 unit. When lysosomal extracts were incubated with bacterial neuraminidase before electrofocusing, the acidic forms of acid phosphatase, arylsulfatase and beta-glucuronidase were largely lost, the isoelectric point of the acidic form of beta-N-acetylhexosaminidase was increased from 4.5 to 6.4, and the isoelectric points of the basic forms of all four hydrolases were increased 0.5-1.5 units. Autoincubation of lysosomal extracts in vitro at pH 5.2 PRODUCED SIMILAR, THOUGH LESS MARKED, effects. cont'd"}
{"id": "PMID:234756", "title": "Changes in electronegativity of lysosomal hydrolases during intracellular transport. An isoelectric-focusing study in subcellular fractions of rat kidney.", "content": "Isoelectric focusing was used to investigate the multiple forms of acid phosphatase, arylsulfatase, beta-glucuronidase, beta-galactosidase and beta-N-acetylhexosaminidase in the following, previously characterized subcellular fractions from rat kidney: a special rough microsomal fraction, enriched up to 9-fold over the homogenate in acid hydrolases; a smooth microsomal fraction; a Golgi membrane fraction enriched about 2.5-fold in acid hydrolases and 10- to 20-fold in several glycosyl transferases; and a lysosomal fraction enriched up to 25-fold in acid hydrolases. The electro-focusing behavior of the hydrolases in these fractions was markedly sensitive to the autolytic changes that occur under acidic conditions, even at 4 degrees C. Autolysis was minimized by extracting fractions in an alkaline medium (0.2% Triton X-100, 0.1 M sodium glycinate buffer, pH 10, 0.1 % p-nitrophenyloxamic acid) and adding p-nitrophenyloxamic acid (0.1 %), AN INHIBITOR OF LYSOSOMAL NEURAMINIDASE AND cathepsin D, to the pH gradient. The enzymes in the lysosomal fraction displayed a characteristic bimodal or trimodal distribution. Arylsulfatase, beta-glucuronidase and beta-N-acetylhexosaminidase occurred in an acidic form with an isoelectric point of 4.4, and a basic form with an isoelectric point of 6.2, 6.7 and 8.0, respectively. Acid phosphatase and beta-galactosidase occurred in an acidic, intermediate and basic form with isoelectric points of about 4. 1, 5.6 and 7.4, respectively. In the special rough microsomal fraction these enzymes were mostly in a basic form with isoelectric points between 7.5 and 9; these were 1-2 units higher than the corresponding basic forms in the lysosomal fraction. Treatment of extracts of the rough microsomal fraction with bacterial neuraminidase raised the isoelectric points of all five hydrolases by 1-2.5 units, indicating the presence of some N-acetylneuraminic acid residues in these basic glycoenzymes. The hydrolases in the Golgi fraction were largely in an acidic form with isoelectric points similar to or lower than those of the corresponding acidic components in the lysosomal fraction. The hydrolases in the smooth microsomal fraction showed isoelectric-focusing patterns intermediate between those in the rough microsomal and the Golgi fractions. These findings support the following scheme for the synthesis, transport and packaging of the lysosomal enzymes. Each hydrolase is synthesized in a restricted portion of the r", "contents": "Changes in electronegativity of lysosomal hydrolases during intracellular transport. An isoelectric-focusing study in subcellular fractions of rat kidney. Isoelectric focusing was used to investigate the multiple forms of acid phosphatase, arylsulfatase, beta-glucuronidase, beta-galactosidase and beta-N-acetylhexosaminidase in the following, previously characterized subcellular fractions from rat kidney: a special rough microsomal fraction, enriched up to 9-fold over the homogenate in acid hydrolases; a smooth microsomal fraction; a Golgi membrane fraction enriched about 2.5-fold in acid hydrolases and 10- to 20-fold in several glycosyl transferases; and a lysosomal fraction enriched up to 25-fold in acid hydrolases. The electro-focusing behavior of the hydrolases in these fractions was markedly sensitive to the autolytic changes that occur under acidic conditions, even at 4 degrees C. Autolysis was minimized by extracting fractions in an alkaline medium (0.2% Triton X-100, 0.1 M sodium glycinate buffer, pH 10, 0.1 % p-nitrophenyloxamic acid) and adding p-nitrophenyloxamic acid (0.1 %), AN INHIBITOR OF LYSOSOMAL NEURAMINIDASE AND cathepsin D, to the pH gradient. The enzymes in the lysosomal fraction displayed a characteristic bimodal or trimodal distribution. Arylsulfatase, beta-glucuronidase and beta-N-acetylhexosaminidase occurred in an acidic form with an isoelectric point of 4.4, and a basic form with an isoelectric point of 6.2, 6.7 and 8.0, respectively. Acid phosphatase and beta-galactosidase occurred in an acidic, intermediate and basic form with isoelectric points of about 4. 1, 5.6 and 7.4, respectively. In the special rough microsomal fraction these enzymes were mostly in a basic form with isoelectric points between 7.5 and 9; these were 1-2 units higher than the corresponding basic forms in the lysosomal fraction. Treatment of extracts of the rough microsomal fraction with bacterial neuraminidase raised the isoelectric points of all five hydrolases by 1-2.5 units, indicating the presence of some N-acetylneuraminic acid residues in these basic glycoenzymes. The hydrolases in the Golgi fraction were largely in an acidic form with isoelectric points similar to or lower than those of the corresponding acidic components in the lysosomal fraction. The hydrolases in the smooth microsomal fraction showed isoelectric-focusing patterns intermediate between those in the rough microsomal and the Golgi fractions. These findings support the following scheme for the synthesis, transport and packaging of the lysosomal enzymes. Each hydrolase is synthesized in a restricted portion of the r"}
{"id": "PMID:234757", "title": "Purification, structure and properties of the respiratory nitrate reductase of Klebsiella aerogenes.", "content": "1. The respiratory nitrate reductase of Klebsiella aerogenes was solubilized from the bacterial membranes by deoxycholate and purified further by means of gel chromatography in the presence of deoxycholate, and anion-exchange chromatography. 2. Dependent on the isolation procedure two different homogeneous forms of the enzyme, having different subunit compositions, can be obtained. These forms are designated nitrate reductase I and nitrate reductase II. Both enzyme preparations are isolated as tetramers having sedimentation constants (s20,w) of 22.1 S and 21.7 S for nitrate reductase I and II, respectively. The nitrate reductase I tetramer has a molecular weight of about 106. 3. In the presence of deoxycholate both enzyme preparations dissociate reversibly into their respective monomeric forms. The monomeric form of nitrate reductase I has a molecular weight of about 260 000 and a sedimentation constant of 9.8 S. For nitrate reductase II these values are 180 000 and 8.5 S, respectively. 4. Nitrate reductase I consists of three different subunits, having molecular weights of 117 000; 57 000 and 52 000, which are present in a 1:1:2 molar ratio, respectively. Nitrate reductase II contains only the subunits with a molecular weight of 117 000 and 57 000 in a equimolar ratio. 5. Treatment at pH 9.5 in the presence of deoxycholate and 0.05 M NaCl or ageing removes the 52 000 Mr subunit from nitrate reductase I. This smallest subunit, in contrast to the other subunits, is a basic protein. 6. The 52 000 Mr subunit has no catalytic function in the intramolecular electron transfer from reduced benzylviologen to nitrate. However, it appears to have a structural function since nitrate reductase II, which lacks this subunit, is much more labile than nitrate reductase I. Inactivation of nitrate reductase II can be prevented by the presence of deoxycholate. 7. The spectrum of the enzyme resembles that of iron-sulfur proteins. No cytochromes or contaminating enzyme activities are present in the purified enzyme. Only reduced benzylviologen was found to be capable of acting as an electron donor. 8. p-Chlormercuribenzoate enhances the enzymatic activity at concentrations of 0.1 mM and lower. At higher p-chlormercuribenzoate concentrations the enzymatic activity is inhibited non-competitively with either nitrate or benzylviologen as a substrate. The inhibition is not counteracted by cysteine.", "contents": "Purification, structure and properties of the respiratory nitrate reductase of Klebsiella aerogenes. 1. The respiratory nitrate reductase of Klebsiella aerogenes was solubilized from the bacterial membranes by deoxycholate and purified further by means of gel chromatography in the presence of deoxycholate, and anion-exchange chromatography. 2. Dependent on the isolation procedure two different homogeneous forms of the enzyme, having different subunit compositions, can be obtained. These forms are designated nitrate reductase I and nitrate reductase II. Both enzyme preparations are isolated as tetramers having sedimentation constants (s20,w) of 22.1 S and 21.7 S for nitrate reductase I and II, respectively. The nitrate reductase I tetramer has a molecular weight of about 106. 3. In the presence of deoxycholate both enzyme preparations dissociate reversibly into their respective monomeric forms. The monomeric form of nitrate reductase I has a molecular weight of about 260 000 and a sedimentation constant of 9.8 S. For nitrate reductase II these values are 180 000 and 8.5 S, respectively. 4. Nitrate reductase I consists of three different subunits, having molecular weights of 117 000; 57 000 and 52 000, which are present in a 1:1:2 molar ratio, respectively. Nitrate reductase II contains only the subunits with a molecular weight of 117 000 and 57 000 in a equimolar ratio. 5. Treatment at pH 9.5 in the presence of deoxycholate and 0.05 M NaCl or ageing removes the 52 000 Mr subunit from nitrate reductase I. This smallest subunit, in contrast to the other subunits, is a basic protein. 6. The 52 000 Mr subunit has no catalytic function in the intramolecular electron transfer from reduced benzylviologen to nitrate. However, it appears to have a structural function since nitrate reductase II, which lacks this subunit, is much more labile than nitrate reductase I. Inactivation of nitrate reductase II can be prevented by the presence of deoxycholate. 7. The spectrum of the enzyme resembles that of iron-sulfur proteins. No cytochromes or contaminating enzyme activities are present in the purified enzyme. Only reduced benzylviologen was found to be capable of acting as an electron donor. 8. p-Chlormercuribenzoate enhances the enzymatic activity at concentrations of 0.1 mM and lower. At higher p-chlormercuribenzoate concentrations the enzymatic activity is inhibited non-competitively with either nitrate or benzylviologen as a substrate. The inhibition is not counteracted by cysteine."}
{"id": "PMID:234758", "title": "EPR studies of protein state transitions in Chromatium ferricytochrome c'.", "content": "Recent magnetic studies have shown that in the pH range 1 to 11 the bacterial heme protein ferricytochrome c' can undergo reversible transitions between various pure high-spin and quantum mechanically mixed (intermediate and high)-spin protein states. The EPR data presented here extend the recent work to high alkaline pH and show that above pH 11.6 reversible transitions occur between various pure high-spin and pure low-spin protein states. The new data and the previous magnetic studies of the protein are discussed in the context of the entatic nature of the iron-porphyrin complex in ferricytochrome c'. EPR data are also provided concerning an anomalous, but reversible, transition to a protein state with reduced heme iron, triggered by freezing and thawing at physiological pH.", "contents": "EPR studies of protein state transitions in Chromatium ferricytochrome c'. Recent magnetic studies have shown that in the pH range 1 to 11 the bacterial heme protein ferricytochrome c' can undergo reversible transitions between various pure high-spin and quantum mechanically mixed (intermediate and high)-spin protein states. The EPR data presented here extend the recent work to high alkaline pH and show that above pH 11.6 reversible transitions occur between various pure high-spin and pure low-spin protein states. The new data and the previous magnetic studies of the protein are discussed in the context of the entatic nature of the iron-porphyrin complex in ferricytochrome c'. EPR data are also provided concerning an anomalous, but reversible, transition to a protein state with reduced heme iron, triggered by freezing and thawing at physiological pH."}
{"id": "PMID:234759", "title": "Study of a haploid yeast strain with an unusually high rDNA content. II. Fractionation of the DNA in preparative Ag+-Cs2SO4 density gradients.", "content": "Yeast DNA has been fractionated in preparative Ag+-C-S2SO4 density gradients. After complexing with silver ions at a pH of about 7, the rDNA appears in a defined heavy satellite component in the gradient. For our particular strain, the satellite represents about 15% of the total nuclear DNA and has been  identified as the gamma-DNA. In alkaline CsCl density gradients, the satellite DNA forms two bands, of which the light component hybridizes with ribosomal RNA.", "contents": "Study of a haploid yeast strain with an unusually high rDNA content. II. Fractionation of the DNA in preparative Ag+-Cs2SO4 density gradients. Yeast DNA has been fractionated in preparative Ag+-C-S2SO4 density gradients. After complexing with silver ions at a pH of about 7, the rDNA appears in a defined heavy satellite component in the gradient. For our particular strain, the satellite represents about 15% of the total nuclear DNA and has been  identified as the gamma-DNA. In alkaline CsCl density gradients, the satellite DNA forms two bands, of which the light component hybridizes with ribosomal RNA."}
{"id": "PMID:234760", "title": "Effect of biotin on ribonucleic acid synthesis.", "content": "A single injection of biotin to biotin-deficient rats produces a two-fold increase in the incorporation, both in vivo and in vitro of precursors into nucleic acids as early as 2 h after the biotin treatment. The specific activity of the precursor pool is not affected by biotin. Analysis of the polysome profile at various times following biotin treatment and a kinetic study of the effect of excess poly(U) on the incorporation of phenylalanine by cell-free amino acid incorporation experiments indicate a marked decrease in messenger-free ribosomes in rat liver after biotin administration.", "contents": "Effect of biotin on ribonucleic acid synthesis. A single injection of biotin to biotin-deficient rats produces a two-fold increase in the incorporation, both in vivo and in vitro of precursors into nucleic acids as early as 2 h after the biotin treatment. The specific activity of the precursor pool is not affected by biotin. Analysis of the polysome profile at various times following biotin treatment and a kinetic study of the effect of excess poly(U) on the incorporation of phenylalanine by cell-free amino acid incorporation experiments indicate a marked decrease in messenger-free ribosomes in rat liver after biotin administration."}
{"id": "PMID:234762", "title": "Observations on the mechanical precipitation of oxy Hb S and other mutants.", "content": "Oxyhemoglobin S exhibits greater mechanical instability than oxyhemoglobin A. The rate of precipitation of Hb S when agitated by vortexing depends upon the geometry of the tube, the volume of the hemoglobin solution, and the concentration of hemoglobin. The rate of precipitation is inversely related to concentration. Precipitation is inhibited by temperatures near 4 degrees C and alkylureas whose protective capacity is approximately proportional to the carbon chain length of the alkyl group. Blocking the beta93 -SH group with parahydroxymercuribenzoate has only a small enhancing effect on the precipitation rate. Other mutants such as Hb Gun Hill, Leiden, (both heat unstable), and C-HARLEM are also unstable. In the case of C-HARLEM, the precipitation rate is greater than that for Hb S. The heat-unstable mutants are not as well protected by cold temperatures or alkyl ureas. D2O has only a minor stabilizing effect on hemoglobin S, but NaCl and related salts markedly enhance precipitation at concentrations of 0.5 M. It is concluded that mechanical instability of oxyhemoglobins is a multifactorial process involving surface denaturation, pH, ionic strength, hydrophobic interactions, protein conformation, and primary protein structure. This phenomenon will require more extensive investigation.", "contents": "Observations on the mechanical precipitation of oxy Hb S and other mutants. Oxyhemoglobin S exhibits greater mechanical instability than oxyhemoglobin A. The rate of precipitation of Hb S when agitated by vortexing depends upon the geometry of the tube, the volume of the hemoglobin solution, and the concentration of hemoglobin. The rate of precipitation is inversely related to concentration. Precipitation is inhibited by temperatures near 4 degrees C and alkylureas whose protective capacity is approximately proportional to the carbon chain length of the alkyl group. Blocking the beta93 -SH group with parahydroxymercuribenzoate has only a small enhancing effect on the precipitation rate. Other mutants such as Hb Gun Hill, Leiden, (both heat unstable), and C-HARLEM are also unstable. In the case of C-HARLEM, the precipitation rate is greater than that for Hb S. The heat-unstable mutants are not as well protected by cold temperatures or alkyl ureas. D2O has only a minor stabilizing effect on hemoglobin S, but NaCl and related salts markedly enhance precipitation at concentrations of 0.5 M. It is concluded that mechanical instability of oxyhemoglobins is a multifactorial process involving surface denaturation, pH, ionic strength, hydrophobic interactions, protein conformation, and primary protein structure. This phenomenon will require more extensive investigation."}
{"id": "PMID:234763", "title": "Breakdown of prothrombin and proconvertin in rats with experimental extrahepatic cholestasis.", "content": "Changes in the half-life of prothrombin and proconvertin were studied in rats with experimental extraphepatic cholestasis induced by ligation of the common bile duct. By the end of the second week of cholestasis the prothrombin activity was reduced almost by half and the proconvertin activity by more than two-thirds compared with the control. Meanwhile the half-life of prothrombin after cholestatsis for 14 days was increased by 1.f h and that of proconvertin by 4.7 h compared with the control. The slower breakdown of prothrombin and proconvertin during cholestasis is regarded as a compensatory reation.", "contents": "Breakdown of prothrombin and proconvertin in rats with experimental extrahepatic cholestasis. Changes in the half-life of prothrombin and proconvertin were studied in rats with experimental extraphepatic cholestasis induced by ligation of the common bile duct. By the end of the second week of cholestasis the prothrombin activity was reduced almost by half and the proconvertin activity by more than two-thirds compared with the control. Meanwhile the half-life of prothrombin after cholestatsis for 14 days was increased by 1.f h and that of proconvertin by 4.7 h compared with the control. The slower breakdown of prothrombin and proconvertin during cholestasis is regarded as a compensatory reation."}
{"id": "PMID:234764", "title": "Effect of o,p'-dichlorodiphenyldichloroethane on glutathione reductase activity and content of SH groups in the dog adrenals.", "content": "The effect of o, p'-dichlorodiphenyldichloroethane (DDD), a compound inducing atrophy of the adrenal cortex and blocking steroid production, on glutathione reductase activity was studied. As a result of feeding dogs with DDD in a dose of 50 mg/kg body weight for 14 days activation of glutathione reducatase took place in the homogenate, cytoplasmic fraction, and disintergrated mitochondria of the adrenals. On the additon of DDD in vitro the activity of the enzyme was unchanged. The content of SH groups expressed per 100 mg tissue was reduced in the homogenate and in all subcellular fractions. If expressed per 100 mg protein in the level of SH groups was lowered only in the microsomes and the disintergrated mitochondria.", "contents": "Effect of o,p'-dichlorodiphenyldichloroethane on glutathione reductase activity and content of SH groups in the dog adrenals. The effect of o, p'-dichlorodiphenyldichloroethane (DDD), a compound inducing atrophy of the adrenal cortex and blocking steroid production, on glutathione reductase activity was studied. As a result of feeding dogs with DDD in a dose of 50 mg/kg body weight for 14 days activation of glutathione reducatase took place in the homogenate, cytoplasmic fraction, and disintergrated mitochondria of the adrenals. On the additon of DDD in vitro the activity of the enzyme was unchanged. The content of SH groups expressed per 100 mg tissue was reduced in the homogenate and in all subcellular fractions. If expressed per 100 mg protein in the level of SH groups was lowered only in the microsomes and the disintergrated mitochondria."}
{"id": "PMID:234765", "title": "Method of investigation of deviations from the normal duration of the cardiac cycle.", "content": "An electronic systems for determining the frequency of deviations from the normal duration of the cardiac cycle is described.", "contents": "Method of investigation of deviations from the normal duration of the cardiac cycle. An electronic systems for determining the frequency of deviations from the normal duration of the cardiac cycle is described."}
{"id": "PMID:234770", "title": "Usefulness of 99mTechnetium pertechnetate in periarteritis nodosa.", "content": "Radioisotopes have a wide range of application in the clinical investigation of many organs. Muscle diseases are an exception in this expanding field. We report here a case of periateritis nodosa in which unusual scintigraphic images were obtained with 99mTc-pertechnetate. The kinetics of this isotope and the scintigraphic changes were followed during treatment and found to be useful clinical tools.", "contents": "Usefulness of 99mTechnetium pertechnetate in periarteritis nodosa. Radioisotopes have a wide range of application in the clinical investigation of many organs. Muscle diseases are an exception in this expanding field. We report here a case of periateritis nodosa in which unusual scintigraphic images were obtained with 99mTc-pertechnetate. The kinetics of this isotope and the scintigraphic changes were followed during treatment and found to be useful clinical tools."}
{"id": "PMID:234772", "title": "The uptake of GABA by clonal nerve glia.", "content": "A number of clonal nerve and glial cell lines are able to accumulate exogenous GABA. The ability of the cells to concentrate GABA is dependent upon external calcium, while the uptake process is sodium dependent and temperature sensititive. GABA uptake by the cell lines is specific with respect to analogue inhibition, but this specificity is different from that observed in brain slices. It is, however, similar to that of glia in the rat sensory ganglia. Although clonal muscle cells can concentrate GABA to a limited extent, a number of other differentiated cells cannot.", "contents": "The uptake of GABA by clonal nerve glia. A number of clonal nerve and glial cell lines are able to accumulate exogenous GABA. The ability of the cells to concentrate GABA is dependent upon external calcium, while the uptake process is sodium dependent and temperature sensititive. GABA uptake by the cell lines is specific with respect to analogue inhibition, but this specificity is different from that observed in brain slices. It is, however, similar to that of glia in the rat sensory ganglia. Although clonal muscle cells can concentrate GABA to a limited extent, a number of other differentiated cells cannot."}
{"id": "PMID:234773", "title": "Cerebral metabolism in hypoxic hypoxia. I. Pattern of activation of glycolysis: a re-evaluation.", "content": "In order to evaluate the pattern of activation of glycolysis in cerebral cortex during hypoxic hypoxia, lightly anesthetized rats were subjected to a lowering of arterial Po2 to about 25 mm Hg and brains were frozen in situ for metabolite analyses either 1, 2, 5, 15 or 30 min following the induction of hypoxia. The lactate and pyruvate concentrations increased progressively during the 30 min period of hypoxia. At 1 and 2 min there were decreases in G-6-P and F-6-P, and increases in FDP, DHAP and 3-PG, indicating activation of phosphofructokinase. At 5 min this pattern of changes was less pronounced and at 15 min it was absent in spite of the fact that the lactate and pyruvate concentrations were further increased. At 30 min F-6-P and F-6-P had further increased but the levels of DHAP, FDP and 3-PG were normal. Evidently, phosphofructokinase activation can only be detected in the early stages of hypoxia, i.e. when the maximal increase in glycolytic flux occurs and before there has been a corresponding activation of other rate-limiting enzymatic steps. Signs of activation of phosphofructokinase were observed in the absence of changes in tissue concentrations of ATP or AMP, with minimal elevation of NH4plus, and in spite of increased (or unchanged) levels of citrate. However, since there were small but significant increases in ADP at 1 and 2 min, and pH-independent decreases in phosphocreatine, the results indicate that hypoxia is accompanied by an initial imbalance between production and utilization of ATP. The metabolic consequences of this imbalance (decrease in phosphocreatine, increases in ADP and P1) may be at least partly responsible for activation of phosphofructokinase.", "contents": "Cerebral metabolism in hypoxic hypoxia. I. Pattern of activation of glycolysis: a re-evaluation. In order to evaluate the pattern of activation of glycolysis in cerebral cortex during hypoxic hypoxia, lightly anesthetized rats were subjected to a lowering of arterial Po2 to about 25 mm Hg and brains were frozen in situ for metabolite analyses either 1, 2, 5, 15 or 30 min following the induction of hypoxia. The lactate and pyruvate concentrations increased progressively during the 30 min period of hypoxia. At 1 and 2 min there were decreases in G-6-P and F-6-P, and increases in FDP, DHAP and 3-PG, indicating activation of phosphofructokinase. At 5 min this pattern of changes was less pronounced and at 15 min it was absent in spite of the fact that the lactate and pyruvate concentrations were further increased. At 30 min F-6-P and F-6-P had further increased but the levels of DHAP, FDP and 3-PG were normal. Evidently, phosphofructokinase activation can only be detected in the early stages of hypoxia, i.e. when the maximal increase in glycolytic flux occurs and before there has been a corresponding activation of other rate-limiting enzymatic steps. Signs of activation of phosphofructokinase were observed in the absence of changes in tissue concentrations of ATP or AMP, with minimal elevation of NH4plus, and in spite of increased (or unchanged) levels of citrate. However, since there were small but significant increases in ADP at 1 and 2 min, and pH-independent decreases in phosphocreatine, the results indicate that hypoxia is accompanied by an initial imbalance between production and utilization of ATP. The metabolic consequences of this imbalance (decrease in phosphocreatine, increases in ADP and P1) may be at least partly responsible for activation of phosphofructokinase."}
{"id": "PMID:234774", "title": "Effects of putative neurotransmitters on neuronal activity in monkey auditory cortex.", "content": "The effects of the putative neurotransmitters norepinephrine (NE), gamma-aminobutyric acid (BAGA), and acetylcholine (ACh) were tested on auditory cortex neurons which were activated acoustically by species-specific vocalizations in awake squirrel monkeys. Five-barrel glass electrodes were used to record the activity single neurons in the superior temporal gyrus and to apply NE, GABA, or ACh microiontophoretically. Poststimulus time histograms and raster displays of neuronal responses to the vocalizations were computed before, during, and after iontophoresis. Dose-dependent inhibition of spontaneous and vocalization-evoked discharge rates was seen with NE and GABA. Generally, excitation was observed with ACh. A given dose of NE or GABA reduced spontaneous activity by a greater proportion than it reduced activity evoked by the vocalizations. During excitatory responses, segments with lower discharge rates were reduced proportionately more than segments with higher discharge rates. Usually, response 'pattern' was not altered by iontophoresis of any of the substances. However, in some cases the differential inhibition of slow activity produced by NE or GABA did result in a 'patern' change. The demonstration that small amounts of locally applied NE and GABA substantially alter the specific neuronal activation produced by vocalizations provides additional evidence that these agents may function as neurotransmitters in this neocortical area and offers clues about their functional significance.", "contents": "Effects of putative neurotransmitters on neuronal activity in monkey auditory cortex. The effects of the putative neurotransmitters norepinephrine (NE), gamma-aminobutyric acid (BAGA), and acetylcholine (ACh) were tested on auditory cortex neurons which were activated acoustically by species-specific vocalizations in awake squirrel monkeys. Five-barrel glass electrodes were used to record the activity single neurons in the superior temporal gyrus and to apply NE, GABA, or ACh microiontophoretically. Poststimulus time histograms and raster displays of neuronal responses to the vocalizations were computed before, during, and after iontophoresis. Dose-dependent inhibition of spontaneous and vocalization-evoked discharge rates was seen with NE and GABA. Generally, excitation was observed with ACh. A given dose of NE or GABA reduced spontaneous activity by a greater proportion than it reduced activity evoked by the vocalizations. During excitatory responses, segments with lower discharge rates were reduced proportionately more than segments with higher discharge rates. Usually, response 'pattern' was not altered by iontophoresis of any of the substances. However, in some cases the differential inhibition of slow activity produced by NE or GABA did result in a 'patern' change. The demonstration that small amounts of locally applied NE and GABA substantially alter the specific neuronal activation produced by vocalizations provides additional evidence that these agents may function as neurotransmitters in this neocortical area and offers clues about their functional significance."}
{"id": "PMID:234775", "title": "Selective uptake of (3H)beta-alanine by glia: association with glial uptake system for GABA.", "content": "On the basis of inhibitor studies it has been suggested that the high-affinity GABA uptake system in glial cells differs in its chemical specificity from that present in nerve terminals. In this paper it has been demonstrated that the GABA analogue, beta-alanine, is almost as good a substrate as GABA itself in the glial cell uptake system whilst not being transported at all into nerve terminals. Not only has [3H]beta-alanine been shown autoradiographically to be exclusively accumulated in glial sites in toeh sensory ganglia and slices of cerebral cortex, but in addition a virtually identical high-affinity uptake process for [3H] beta-alanine was demonstrated at both these sites. Furthermore, non-radioactive GABA was shown to be an equipotent inhibitor of [3H]beta-alanine uptake in sensory ganglia as well as in both small slices and synaptosomes prepared from cerebral cortical tissue, Finally, the competitive inhibition kinetics of GABA on [3H]beta-alanine uptake in cortical slices furnishes proof that intact glial sites of GABA uptake were present in such slices in addition to the more prominent and well documented uptake system in nerve terminals. The possible imporatnce of such glial fragments in brain slice and crude synaptosomal preparations is discussed.", "contents": "Selective uptake of (3H)beta-alanine by glia: association with glial uptake system for GABA. On the basis of inhibitor studies it has been suggested that the high-affinity GABA uptake system in glial cells differs in its chemical specificity from that present in nerve terminals. In this paper it has been demonstrated that the GABA analogue, beta-alanine, is almost as good a substrate as GABA itself in the glial cell uptake system whilst not being transported at all into nerve terminals. Not only has [3H]beta-alanine been shown autoradiographically to be exclusively accumulated in glial sites in toeh sensory ganglia and slices of cerebral cortex, but in addition a virtually identical high-affinity uptake process for [3H] beta-alanine was demonstrated at both these sites. Furthermore, non-radioactive GABA was shown to be an equipotent inhibitor of [3H]beta-alanine uptake in sensory ganglia as well as in both small slices and synaptosomes prepared from cerebral cortical tissue, Finally, the competitive inhibition kinetics of GABA on [3H]beta-alanine uptake in cortical slices furnishes proof that intact glial sites of GABA uptake were present in such slices in addition to the more prominent and well documented uptake system in nerve terminals. The possible imporatnce of such glial fragments in brain slice and crude synaptosomal preparations is discussed."}
{"id": "PMID:234776", "title": "The cerebral ventricles as the avenue for the dipsogenic action of intracranial angiotensin.", "content": "Using low doses of angiotensin II (1-128 ng), a mapping study was carried out to redefine the region within the brain from which the dipsogenic response can be elicited. The most sensitive sites were either close to the anterior cerebral ventricles or were at the tips of cannulae that traversed a ventricular space en route to the tissue site. Conversely, insensitive sites were remote from the ventricles and were not reached by cannulae with a ventricular trajectory. Therefore, a thorough assessment of the role of the ventricular system in the angiotensin thirst phenomenon was demanded. Further studies revealed that direct intraventricular injections were as effective as those made into any tissue site tested. Also, regardless of the similarity in the sites of their termination, cannulae which passed through a ventricular space en route to that site yielded highly sensitive preparations whereas those which did not were insensitive to the hormone. Autoradiographic and radioassay studies showed that tritiated angiotensin II injected into anterior diencephalic tissue through cannulae which traversed the ventricles was rapidly distributed throughout the ventricular system. Thus, efflux of the injected material up the cannula shaft and its entry into the ventricular system is essential for a dipsogenic response to low doses of the hormone. These results support the hypothesis of a periventricular receptor site for angiotensin. It is suggested that systemically generated angiotensin and angiotensin endogenous to the brain may use the ventricular route as a means of access to the sensitive periventricular site.", "contents": "The cerebral ventricles as the avenue for the dipsogenic action of intracranial angiotensin. Using low doses of angiotensin II (1-128 ng), a mapping study was carried out to redefine the region within the brain from which the dipsogenic response can be elicited. The most sensitive sites were either close to the anterior cerebral ventricles or were at the tips of cannulae that traversed a ventricular space en route to the tissue site. Conversely, insensitive sites were remote from the ventricles and were not reached by cannulae with a ventricular trajectory. Therefore, a thorough assessment of the role of the ventricular system in the angiotensin thirst phenomenon was demanded. Further studies revealed that direct intraventricular injections were as effective as those made into any tissue site tested. Also, regardless of the similarity in the sites of their termination, cannulae which passed through a ventricular space en route to that site yielded highly sensitive preparations whereas those which did not were insensitive to the hormone. Autoradiographic and radioassay studies showed that tritiated angiotensin II injected into anterior diencephalic tissue through cannulae which traversed the ventricles was rapidly distributed throughout the ventricular system. Thus, efflux of the injected material up the cannula shaft and its entry into the ventricular system is essential for a dipsogenic response to low doses of the hormone. These results support the hypothesis of a periventricular receptor site for angiotensin. It is suggested that systemically generated angiotensin and angiotensin endogenous to the brain may use the ventricular route as a means of access to the sensitive periventricular site."}
{"id": "PMID:234778", "title": "The soluble adenosine triphosphatase of Thiobacillus ferrooxidans.", "content": "Adenosine triphosphatase (ATPase) from Thiobacillus ferrooxidans was purified 55-fold. Polyacrylamide gel electrophoresis of the most purified fraction showed only one major band; histochemical analysis showed that the ATPase activity was associated with this band. The pH optimum is 9-10. The enzyme hydrolyzed ATP stoichiometrically to ADP and inorganic phosphate, the Km for this substrate being 7.75 times 10-3 M. GTP and ITP are alternate substrates, the Km values for these being 6.71 times 10-3 M and 3.12 times 10-3 M, respectively. ADP is slightly hydrolyzed. Magnesium, manganese, and calcium can serve as cofactors; Km values for these are 2.0 times 10-3 M, 9.4 times 10-4 M, and 8.0 times 10-4 M, respectively. The enzyme activity was not activated by either sodium or potassium, but a combination of the two ions were inhibitory. Azide and p-hydroxymercuribenzoate strongly inhibited the enzyme activity, whereas cyanide, dinitrophenol, and N,N'-dicyclohexylcarbodiimide (DCCD) were without effect. The enzyme was cold labile at 0 degrees-C, but was more stable at 18-24 degrees-C.", "contents": "The soluble adenosine triphosphatase of Thiobacillus ferrooxidans. Adenosine triphosphatase (ATPase) from Thiobacillus ferrooxidans was purified 55-fold. Polyacrylamide gel electrophoresis of the most purified fraction showed only one major band; histochemical analysis showed that the ATPase activity was associated with this band. The pH optimum is 9-10. The enzyme hydrolyzed ATP stoichiometrically to ADP and inorganic phosphate, the Km for this substrate being 7.75 times 10-3 M. GTP and ITP are alternate substrates, the Km values for these being 6.71 times 10-3 M and 3.12 times 10-3 M, respectively. ADP is slightly hydrolyzed. Magnesium, manganese, and calcium can serve as cofactors; Km values for these are 2.0 times 10-3 M, 9.4 times 10-4 M, and 8.0 times 10-4 M, respectively. The enzyme activity was not activated by either sodium or potassium, but a combination of the two ions were inhibitory. Azide and p-hydroxymercuribenzoate strongly inhibited the enzyme activity, whereas cyanide, dinitrophenol, and N,N'-dicyclohexylcarbodiimide (DCCD) were without effect. The enzyme was cold labile at 0 degrees-C, but was more stable at 18-24 degrees-C."}
{"id": "PMID:234779", "title": "Loss of primary alkylsulfatase and secondary alkylsulfatases (S-1 and S-2) from Pseudomonas C12B: effect of culture conditions, cell-washing procedures, and osmotic shock.", "content": "Secondary alkylsulfatases (S-1 and S-2) were detected in Pseudomonas C12B cultured in minimal media lacking alkylsulfatases. The synthesis of these enzymes was not repressed by SO4-2- and L-cysteine or derepressed by L-methionine. Growth on 4% sodium citrate caused a 98% loss in the secondary alkylsulfatase activity of cells and 9% of this activity was detected in the culture medium. Citrate (20 mM) inhibited the activity of cell extracts (18%) but the inhibition was reversible by dialysis. The primary alkylsulfatase content of cells was not diminished by growth on citrate. The MgCl2 concentration of the medium also influenced the cellular levels of secondary alkylsulfatase. Bacteria grown on MgCl2 (0.05 mM - 40 mM) exhibited progressively increasing activity while the converse distribution was observed for activity present in the medium after growth at each MgCl2 concentration. Both primary and secondary alkylsulfatases were released when cells were either subjected to osmotic shock or treated for cell wall removal. Cells washed with 0.085 M sodium citrate-10 mM Tris-20%sucrose released roughly 87% of both enzymes and MgCl2 (0.04 M) inhibited the release of primary alkylsulfatase by 11% and secondary alkylsulfatase by 50%. It is suggested that citrate chelates divalent cations necessary for the attachment of secondary alkylsulfatase at the cell periphery.", "contents": "Loss of primary alkylsulfatase and secondary alkylsulfatases (S-1 and S-2) from Pseudomonas C12B: effect of culture conditions, cell-washing procedures, and osmotic shock. Secondary alkylsulfatases (S-1 and S-2) were detected in Pseudomonas C12B cultured in minimal media lacking alkylsulfatases. The synthesis of these enzymes was not repressed by SO4-2- and L-cysteine or derepressed by L-methionine. Growth on 4% sodium citrate caused a 98% loss in the secondary alkylsulfatase activity of cells and 9% of this activity was detected in the culture medium. Citrate (20 mM) inhibited the activity of cell extracts (18%) but the inhibition was reversible by dialysis. The primary alkylsulfatase content of cells was not diminished by growth on citrate. The MgCl2 concentration of the medium also influenced the cellular levels of secondary alkylsulfatase. Bacteria grown on MgCl2 (0.05 mM - 40 mM) exhibited progressively increasing activity while the converse distribution was observed for activity present in the medium after growth at each MgCl2 concentration. Both primary and secondary alkylsulfatases were released when cells were either subjected to osmotic shock or treated for cell wall removal. Cells washed with 0.085 M sodium citrate-10 mM Tris-20%sucrose released roughly 87% of both enzymes and MgCl2 (0.04 M) inhibited the release of primary alkylsulfatase by 11% and secondary alkylsulfatase by 50%. It is suggested that citrate chelates divalent cations necessary for the attachment of secondary alkylsulfatase at the cell periphery."}
{"id": "PMID:234780", "title": "Yeast-like growth of Mucor alternans (van Tieghem) in tissue-culture medium 199.", "content": "Mucor alternans(van Tieghem) was found to be a diphasic species in that it grew exclusively in the yeast-like budding phase under anaerobic conditions in the complex medium yeast extract-peptone-glucose broth and in tissue-culture medium 199. In the latter medium this growth form occurred also at 37C, at an initial pH of 7.2, and at glucose concentrations of 0.1 and 1.0%. The authors suggest that because of its synthetic nature the tissue-culture medium could be used with advantage in the study of nutritional requirements of dimorphic mucors.", "contents": "Yeast-like growth of Mucor alternans (van Tieghem) in tissue-culture medium 199. Mucor alternans(van Tieghem) was found to be a diphasic species in that it grew exclusively in the yeast-like budding phase under anaerobic conditions in the complex medium yeast extract-peptone-glucose broth and in tissue-culture medium 199. In the latter medium this growth form occurred also at 37C, at an initial pH of 7.2, and at glucose concentrations of 0.1 and 1.0%. The authors suggest that because of its synthetic nature the tissue-culture medium could be used with advantage in the study of nutritional requirements of dimorphic mucors."}
{"id": "PMID:234781", "title": "Stable isotope fractionation by Clostridium pasteurianum. 1. 34S/32S: inverse isotope effects during SO4-2- and SO3-2- reduction.", "content": "During growth on minimal salts--sucrose media supplemented with various concentrations (10-4-10-2 M) of sodium sulfate, Clostridium pasteurianum grew at a normal rate and only evolved sulfide in late stages of growth on 10-2 M SO4-2-. The evolved sulfide was slightly enriched in 34S as compared to the medium sulfur. On the other hand, sulfide was evolved during growth on all concentrations of sulfite tested. Large normal and inverse isotopic effects were observed in the evolved sulfide during SO3-2- reductions. In contrast, the intracellular sulfur showed much smaller fractionations. The complexity of the isotopic patterns suggests that a dissimilatory sulfite reductase system may be induced by high concentrations of sulfite.", "contents": "Stable isotope fractionation by Clostridium pasteurianum. 1. 34S/32S: inverse isotope effects during SO4-2- and SO3-2- reduction. During growth on minimal salts--sucrose media supplemented with various concentrations (10-4-10-2 M) of sodium sulfate, Clostridium pasteurianum grew at a normal rate and only evolved sulfide in late stages of growth on 10-2 M SO4-2-. The evolved sulfide was slightly enriched in 34S as compared to the medium sulfur. On the other hand, sulfide was evolved during growth on all concentrations of sulfite tested. Large normal and inverse isotopic effects were observed in the evolved sulfide during SO3-2- reductions. In contrast, the intracellular sulfur showed much smaller fractionations. The complexity of the isotopic patterns suggests that a dissimilatory sulfite reductase system may be induced by high concentrations of sulfite."}
{"id": "PMID:234782", "title": "Occurence of lactose-negative mutants in chemostat cultures of lactic streptococci.", "content": "Batch and chemostat cultures of Streptococcus cremoris HP and Streptococcus lactis 829 were examined for lactose-hegative (lac-)mutants on indicator agar. In batch cultures, S. cremoris HP gave less than 1% of the total count as lac- colonies while S. lactis 829 consistently contained about 15% of the total as lac- colonies. In chemostat cultures of S. cremoris HP in 2% skim milk containing casamino acids and yeast extract (0.1% each), the percentage of lac- colonies increased markedly when the temperature of growth was 18 degrees C but not when the temperature of growth was 25 degrees C. The percentage of lac- colonies in chemostat cultures in the skim milk medium at 25 degrees C was about the same as that in batch cultures. On the other hand, when chemostat cultures of S. lactis 829 in the skim milk medium were grown at several temperatures between 18 and 33 degrees C, the percentage of lac- colonies was markedly lower than that found in batch cultures of this organism. Cultivation of S. cremoris HP in chemostats with yeast extract-glucose broth at low temperature (18 degrees C) resulted in a selection of cells giving lac- colonies and atypical (small) lac+ colonies. The results show that cultivation of S. cremoris HP and S. lactis 829 in chemostats sometimes gave rise to altered populations. Conditions causing a change in one organism did not necessarily cause a similar change in the other. The results indicate that the successful propagation of lactic streptococci in chemostats for use as starter cultures in the dairy industry will require the careful establishment of optimum conditions for every strain so as to minimize the possible selection of undesirable populations.", "contents": "Occurence of lactose-negative mutants in chemostat cultures of lactic streptococci. Batch and chemostat cultures of Streptococcus cremoris HP and Streptococcus lactis 829 were examined for lactose-hegative (lac-)mutants on indicator agar. In batch cultures, S. cremoris HP gave less than 1% of the total count as lac- colonies while S. lactis 829 consistently contained about 15% of the total as lac- colonies. In chemostat cultures of S. cremoris HP in 2% skim milk containing casamino acids and yeast extract (0.1% each), the percentage of lac- colonies increased markedly when the temperature of growth was 18 degrees C but not when the temperature of growth was 25 degrees C. The percentage of lac- colonies in chemostat cultures in the skim milk medium at 25 degrees C was about the same as that in batch cultures. On the other hand, when chemostat cultures of S. lactis 829 in the skim milk medium were grown at several temperatures between 18 and 33 degrees C, the percentage of lac- colonies was markedly lower than that found in batch cultures of this organism. Cultivation of S. cremoris HP in chemostats with yeast extract-glucose broth at low temperature (18 degrees C) resulted in a selection of cells giving lac- colonies and atypical (small) lac+ colonies. The results show that cultivation of S. cremoris HP and S. lactis 829 in chemostats sometimes gave rise to altered populations. Conditions causing a change in one organism did not necessarily cause a similar change in the other. The results indicate that the successful propagation of lactic streptococci in chemostats for use as starter cultures in the dairy industry will require the careful establishment of optimum conditions for every strain so as to minimize the possible selection of undesirable populations."}
{"id": "PMID:234783", "title": "Membrane mutations and production of enterotoxin B and alpha hemolysin in Staphylococcus aureus.", "content": "Staphylococcus aureus strain S-6, which produces enterotoxin type B (SEB), and strain 10-275, a high toxin-producing mutant derived from S-6, display pronounced differences in dye sensitivity, osmotic stability, and bacitracin sensitivity. Such characteristics are consistent with the concept that strain 10-275 is a membrane mutant of strain S-6. Some membrane mutants of S. aureus strain 14458 exhibit about two- to three-fold increases in SEB production whereas other membrane mutants show about twofold increases in alpha-hemolysin production. It is suggested that specific and independent membrane mutations control the secretory processes resulting in the extracellular elaboration of these exoproteins.", "contents": "Membrane mutations and production of enterotoxin B and alpha hemolysin in Staphylococcus aureus. Staphylococcus aureus strain S-6, which produces enterotoxin type B (SEB), and strain 10-275, a high toxin-producing mutant derived from S-6, display pronounced differences in dye sensitivity, osmotic stability, and bacitracin sensitivity. Such characteristics are consistent with the concept that strain 10-275 is a membrane mutant of strain S-6. Some membrane mutants of S. aureus strain 14458 exhibit about two- to three-fold increases in SEB production whereas other membrane mutants show about twofold increases in alpha-hemolysin production. It is suggested that specific and independent membrane mutations control the secretory processes resulting in the extracellular elaboration of these exoproteins."}
{"id": "PMID:234784", "title": "Thiobacillus acidophilus sp. nov.; isolation and some physiological characteristics.", "content": "After a brief exposition to glucose, Thiobacillus acidophilus was isolated from a culture of iron-grown T. ferrooxidans. Physicochemical analysis of its DNA showed a G+C content of 62.9-63.2%. The new isolate grows best at 25-30 degrees C and at pH 3.0. Growth is possible between pH 1.5 and 6.0. Thiobacillus acidophilus is apparently strictly aerobic. Ammonium salts are the only suitable source of nitrogen. The bacterium is a facultative autotroph. In addition to elemental sulfur, it obtains energy from organic compounds such as D-glucose, D-galactose, D-fructose, D-mannitol, D-xylose, D-ribose, D-arabinose, L-arabinose, sucrose, sodium citrate, malic acid,dl-aspartic acid, and dl-glutamic acid. Thiobacillus acidophilus possesses the key enzymes of the tricarboxylic acid (TCA) cycle including NAD-and NADP-linked isocitric dehydrogenase and alpha-ketoglutarate dehydrogenase, and the key enzymes of the hexose monophosphate pathway (glucose-6-phosphate and 6-phosphogluconate dehydrogenase, and fructose 1,6-diphosphate aldolase). NADH oxidase has been found in particulate fraction of extracts. Rhodanese and thiosulfate oxidase have also been detected.", "contents": "Thiobacillus acidophilus sp. nov.; isolation and some physiological characteristics. After a brief exposition to glucose, Thiobacillus acidophilus was isolated from a culture of iron-grown T. ferrooxidans. Physicochemical analysis of its DNA showed a G+C content of 62.9-63.2%. The new isolate grows best at 25-30 degrees C and at pH 3.0. Growth is possible between pH 1.5 and 6.0. Thiobacillus acidophilus is apparently strictly aerobic. Ammonium salts are the only suitable source of nitrogen. The bacterium is a facultative autotroph. In addition to elemental sulfur, it obtains energy from organic compounds such as D-glucose, D-galactose, D-fructose, D-mannitol, D-xylose, D-ribose, D-arabinose, L-arabinose, sucrose, sodium citrate, malic acid,dl-aspartic acid, and dl-glutamic acid. Thiobacillus acidophilus possesses the key enzymes of the tricarboxylic acid (TCA) cycle including NAD-and NADP-linked isocitric dehydrogenase and alpha-ketoglutarate dehydrogenase, and the key enzymes of the hexose monophosphate pathway (glucose-6-phosphate and 6-phosphogluconate dehydrogenase, and fructose 1,6-diphosphate aldolase). NADH oxidase has been found in particulate fraction of extracts. Rhodanese and thiosulfate oxidase have also been detected."}
{"id": "PMID:234785", "title": "Optimum conditions for initiation of filamentation in Candida albicans.", "content": "A medium that initially produced filaments from almost all of its Candida albicans blastospore inoculum contained 1% mycological peptone and 0.2% glucose, final pH 7.4-7.5. The medium was inoculated to 10-6 cells/ml and incubated at 40 degrees C. Reversion to secondary blastospores began at a mean of 2.4 h after inoculation. The patterns of utilization of growth nutrients during optimal mycelial growth showed no correlation with the events of filamentation.", "contents": "Optimum conditions for initiation of filamentation in Candida albicans. A medium that initially produced filaments from almost all of its Candida albicans blastospore inoculum contained 1% mycological peptone and 0.2% glucose, final pH 7.4-7.5. The medium was inoculated to 10-6 cells/ml and incubated at 40 degrees C. Reversion to secondary blastospores began at a mean of 2.4 h after inoculation. The patterns of utilization of growth nutrients during optimal mycelial growth showed no correlation with the events of filamentation."}
{"id": "PMID:234787", "title": "Aerosol BCG treatment of carcinoma metastatic to the lung: a phase I study.", "content": "BCG (TICE) was safely administered to 15 patients with metastatic cancer to the lungs in weekly doses of up to 3 X 107 organisms by the aerosol route. The aerosol route of administration is associated in approximately 33% of the doses with a toxicity syndrome of malaise, fever, and chills beginning 4 to 8 hours after treatment and ending within 24-36 hours. This syndrome is experienced by all patients and symptoms gradually subside with continuation of therapy. No hepatic or pulmonary toxicity was documented during the 221 treatment doses.", "contents": "Aerosol BCG treatment of carcinoma metastatic to the lung: a phase I study. BCG (TICE) was safely administered to 15 patients with metastatic cancer to the lungs in weekly doses of up to 3 X 107 organisms by the aerosol route. The aerosol route of administration is associated in approximately 33% of the doses with a toxicity syndrome of malaise, fever, and chills beginning 4 to 8 hours after treatment and ending within 24-36 hours. This syndrome is experienced by all patients and symptoms gradually subside with continuation of therapy. No hepatic or pulmonary toxicity was documented during the 221 treatment doses."}
{"id": "PMID:234788", "title": "Treatment of an established graft-versus-host reaction in AKR mice by adoptive immunotherapy.", "content": "A model system in AKR mice for the induction and cure of a clinically evident graft-versus-host disease is reported. Graft-versus-host disease is inititated by i.p. injections of ecyclophosphamide (250 mg/kg body weitht ) into female AKR mice, on Day 0. This is followed by i.v. injections of 45 x 10-6 normal spleen cells (NSC) from male C57BL/6J mice. Median survival time for these mice is 33.4 plus or minus 4.5 days. Following the administration of C57BL/6J NSC, AKR mice were rescued from graft-versus-host disease by the following treatment protocol: (a) Day 6, 35 x 10-6 DBA/2 NSC given i.v.; (b) Day 10, cyclophosphamide i.p. (150 mg/kg body weight); (c) Days 11 and 26, 35 x 10-6 AKR NSC given i.v. These experiments demonstrate that graft-versus-host reaction can be elminiated by coupling a graft-versus-host reaction with a graft-versus-graft reaction and restoring the host by immunocompetent syngeneic cells.", "contents": "Treatment of an established graft-versus-host reaction in AKR mice by adoptive immunotherapy. A model system in AKR mice for the induction and cure of a clinically evident graft-versus-host disease is reported. Graft-versus-host disease is inititated by i.p. injections of ecyclophosphamide (250 mg/kg body weitht ) into female AKR mice, on Day 0. This is followed by i.v. injections of 45 x 10-6 normal spleen cells (NSC) from male C57BL/6J mice. Median survival time for these mice is 33.4 plus or minus 4.5 days. Following the administration of C57BL/6J NSC, AKR mice were rescued from graft-versus-host disease by the following treatment protocol: (a) Day 6, 35 x 10-6 DBA/2 NSC given i.v.; (b) Day 10, cyclophosphamide i.p. (150 mg/kg body weight); (c) Days 11 and 26, 35 x 10-6 AKR NSC given i.v. These experiments demonstrate that graft-versus-host reaction can be elminiated by coupling a graft-versus-host reaction with a graft-versus-graft reaction and restoring the host by immunocompetent syngeneic cells."}
{"id": "PMID:234789", "title": "Graft versus leukemia without fatal graft-versus-host disease in AKR mice.", "content": "BW 5147 leukemia in AKR mice has been successfully treated by adoptive immunotherapy using allogeneic spleen cells from C57BL/6J mice. Graft-versus-host reaction was prevented by treatment with spleen cells from a second allogeneic strain (CBA, H-2 identical with AKR), followed by cycloposphamide and syngeneic spleen cells. Successful treatment of leukemia without graft-versus-host reaction is dependent upon a close relationship at the H-2 locus between the second allogeneic donor and the host AKR mice, since cells from a non-H-2 identical donor (DBA/2) do not increase survival. The doses of cyclophosphamide and of C57BL/6J spleen cells are also parameters of critical importance in successful treatment.", "contents": "Graft versus leukemia without fatal graft-versus-host disease in AKR mice. BW 5147 leukemia in AKR mice has been successfully treated by adoptive immunotherapy using allogeneic spleen cells from C57BL/6J mice. Graft-versus-host reaction was prevented by treatment with spleen cells from a second allogeneic strain (CBA, H-2 identical with AKR), followed by cycloposphamide and syngeneic spleen cells. Successful treatment of leukemia without graft-versus-host reaction is dependent upon a close relationship at the H-2 locus between the second allogeneic donor and the host AKR mice, since cells from a non-H-2 identical donor (DBA/2) do not increase survival. The doses of cyclophosphamide and of C57BL/6J spleen cells are also parameters of critical importance in successful treatment."}
{"id": "PMID:234790", "title": "Therapy in an intracerebral murine glioma model, using Bacillus Calmette-Gu\u00e9rin, neuraminidase-treated tumor cells, and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea.", "content": "The s.c.-propagated murine glioma, GL-26, was established in tissue culture. The tissue culture line, with a doubling time of 36 hr, was used as the common source for all tumor cells. Suspensions of the tumor cells were transplanted intracerebrally in mice to produce an anaplastic ependymoblastoma. In vitro 51-Cr cytotoxicity assays did not detect any cellular immunity against GL-26 tumor cells in animals bearing either s.c. or i.c. tumors, indicating that the tumor itself is not highly immunogenic. Howeveer,significant cellular cytotoxicity was elicited in non-tumor-bearing animals by immunization with Vibrio cholerae neuramini-animals by immunization with Vibrio cholerae neuraminidase and mitomycin C-treated tumor cells plus complete Freund's adjuvant. In vivo therapy studies revealed significant increases in survival of animals preimmunized with V. cholerae neuraminidase- and mitomycin C-treated cells plus complete Freund's adjuvant. 1(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea, when given i.p. on Day 3 or 12 after tumor challenge, also resulted in significant increases in survival. Furthermore, the effects of 1-(2-chloroethyl)- 3-cyclohexyl-1-nitrosourea and preimmunization were additive, with significanchloroethyl)-3-cyclohexyl-1-nitrosourea. In contrast to results reported for several extracranial tumor systems, immunotherapy, using either V.cholerae neuraminidase- and mitomycin-treated tumor cells, Bacillus Calmette-Guerin, or both, beginning 3 0r 4 days after tumor challenge, did not produce any significant increases in survival.", "contents": "Therapy in an intracerebral murine glioma model, using Bacillus Calmette-Gu\u00e9rin, neuraminidase-treated tumor cells, and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea. The s.c.-propagated murine glioma, GL-26, was established in tissue culture. The tissue culture line, with a doubling time of 36 hr, was used as the common source for all tumor cells. Suspensions of the tumor cells were transplanted intracerebrally in mice to produce an anaplastic ependymoblastoma. In vitro 51-Cr cytotoxicity assays did not detect any cellular immunity against GL-26 tumor cells in animals bearing either s.c. or i.c. tumors, indicating that the tumor itself is not highly immunogenic. Howeveer,significant cellular cytotoxicity was elicited in non-tumor-bearing animals by immunization with Vibrio cholerae neuramini-animals by immunization with Vibrio cholerae neuraminidase and mitomycin C-treated tumor cells plus complete Freund's adjuvant. In vivo therapy studies revealed significant increases in survival of animals preimmunized with V. cholerae neuraminidase- and mitomycin C-treated cells plus complete Freund's adjuvant. 1(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea, when given i.p. on Day 3 or 12 after tumor challenge, also resulted in significant increases in survival. Furthermore, the effects of 1-(2-chloroethyl)- 3-cyclohexyl-1-nitrosourea and preimmunization were additive, with significanchloroethyl)-3-cyclohexyl-1-nitrosourea. In contrast to results reported for several extracranial tumor systems, immunotherapy, using either V.cholerae neuraminidase- and mitomycin-treated tumor cells, Bacillus Calmette-Guerin, or both, beginning 3 0r 4 days after tumor challenge, did not produce any significant increases in survival."}
{"id": "PMID:234791", "title": "The effect of B-cell immunosuppression on age-related resistance of chickens to Marek's disease.", "content": "Chickens were bursectomized by cyclophosphamide treatment at hatching. At 8 or 9 weeks of age, bursectomized and unbursectomized hatchmates, free from prior infection, were challenged with pathogenic Marek's disease virus. Oncogenicity of the virus inoculum was confirmed by inoculating 1-day-old susceptible chickens. At the time of virus challenge, blood cells from the cyclophosphamide-treated chickens were able to mount a vigorous graft-versus-host reaction in allogeneic embryos. This ability indicated that the thymus function was intact. There were no significant differences in Marek's disease response of bursectomized and unbursectomized chickens, in spite of a severe defect in the bursa-dependent functions in the bursectomized chickens. Some bursa-deficient chickens had non-proliferating, presumably regressing lesions in peripheral nerves. Because these lesions lacked plasma cells, it was concluded that the plasma cell may not play a functional  role in recovery from Marek's disease.", "contents": "The effect of B-cell immunosuppression on age-related resistance of chickens to Marek's disease. Chickens were bursectomized by cyclophosphamide treatment at hatching. At 8 or 9 weeks of age, bursectomized and unbursectomized hatchmates, free from prior infection, were challenged with pathogenic Marek's disease virus. Oncogenicity of the virus inoculum was confirmed by inoculating 1-day-old susceptible chickens. At the time of virus challenge, blood cells from the cyclophosphamide-treated chickens were able to mount a vigorous graft-versus-host reaction in allogeneic embryos. This ability indicated that the thymus function was intact. There were no significant differences in Marek's disease response of bursectomized and unbursectomized chickens, in spite of a severe defect in the bursa-dependent functions in the bursectomized chickens. Some bursa-deficient chickens had non-proliferating, presumably regressing lesions in peripheral nerves. Because these lesions lacked plasma cells, it was concluded that the plasma cell may not play a functional  role in recovery from Marek's disease."}
{"id": "PMID:234792", "title": "Induction of enzymes by glucagon, glucose repression, adenosine 3',5'-monophosphate concentration during carcinogenesis and in Morris 6918A hepatoma.", "content": "We have studied glucagon induction of enzymes, adenosine 3', 5'-monophosphate concentrations, and glucose repression in Morris 9618A hepatoma and in the liver of rats fed, for periods of up to 5 weeks, a solid diet containing 2-acetylaminofluorene or 3'-methyl-4-dimethylaminoazobenzene. While the basal levels of the enzymes serine dehydratase and tyrosine aminotransferase were the same as those found in control rats, their response to glucagon was reduced in experimental animals with or without tumors. However, the basal or glucagon-stimulated levels of adenosine 3', 5'-monophosphate in the liver of rats given the carcinogens were not changed. In Morris 9618A hepatoma, these parameters were, likewise, comparable to those in control animals. When glucose was administered to carcinogen-treated or tumor-bearing rats that had received a single dose of glucagon, there was no suppression of the increase in activity of serine dehydratase and tyrosine aminotransferase observed after glucagon treatment alone. The loss of glucose repression was seen already at 2 to 3 weeks following initiation of the carcinogenic diets. As previous studies had established for normal liver, the hormone-induced high levels of adenosine 3',5'-monophosphate remained unchanged also in Morris 9618A hepatoma and in rats given carcinogen. These results indicate that alterations in enzyme induction during chemical carcinogenesis are not the consequence of changes in adenosine 3',5'-monophosphate levels caused by carcinogens. The early disappearance of the glucose effect, which persists in slow-growing hepatomas, may be an expression of interference by carcinogens with the translation apparatus of the hepatic cell.", "contents": "Induction of enzymes by glucagon, glucose repression, adenosine 3',5'-monophosphate concentration during carcinogenesis and in Morris 6918A hepatoma. We have studied glucagon induction of enzymes, adenosine 3', 5'-monophosphate concentrations, and glucose repression in Morris 9618A hepatoma and in the liver of rats fed, for periods of up to 5 weeks, a solid diet containing 2-acetylaminofluorene or 3'-methyl-4-dimethylaminoazobenzene. While the basal levels of the enzymes serine dehydratase and tyrosine aminotransferase were the same as those found in control rats, their response to glucagon was reduced in experimental animals with or without tumors. However, the basal or glucagon-stimulated levels of adenosine 3', 5'-monophosphate in the liver of rats given the carcinogens were not changed. In Morris 9618A hepatoma, these parameters were, likewise, comparable to those in control animals. When glucose was administered to carcinogen-treated or tumor-bearing rats that had received a single dose of glucagon, there was no suppression of the increase in activity of serine dehydratase and tyrosine aminotransferase observed after glucagon treatment alone. The loss of glucose repression was seen already at 2 to 3 weeks following initiation of the carcinogenic diets. As previous studies had established for normal liver, the hormone-induced high levels of adenosine 3',5'-monophosphate remained unchanged also in Morris 9618A hepatoma and in rats given carcinogen. These results indicate that alterations in enzyme induction during chemical carcinogenesis are not the consequence of changes in adenosine 3',5'-monophosphate levels caused by carcinogens. The early disappearance of the glucose effect, which persists in slow-growing hepatomas, may be an expression of interference by carcinogens with the translation apparatus of the hepatic cell."}
{"id": "PMID:234801", "title": "Renaturation effects of cis and trans platinum II and IV compounds on calf thymus deoxyribonucleic acid.", "content": "The effects of cis dichlorodiammine platinum [cis Pt(II)], trans dichlorodiammine platinum (trans Pt(II)], cis tetrachlorodiammine platinum [cis Pt(IV)], trans tetrachlorodiammine platinum [trans Pt(IV)], and ethylenediaminedichloride platinum [Pt(II)en] on the absorption spectra, and thermal hyper- and hypochromicity of calf thymus DNA were investigated. Platinum-induced renaturation was studied as one parameter of interstrand cross-linking. Based on a DNA cross-linking hypothesis, the tumor-inhibitory platinum compounds cis Pt(II), cis Pt(IV) and Pt(II)en would be expected to induce renaturation following thermal denaturation, whereas the ineffective drugs, trans Pt(II) and trans Pt(IV) would not. All five bind to DNA in such a way as to induce renaturation. However, cis Pt(IV) requires at least a 3- to 4-fold longer incubation time than is required by the other compounds to form the coordination bonds necessary for renaturation. Maximum renaturation with all compounds was observed at a molar Pt/base ratio of 0.05 except cis Pt(IV), with which it was 0.25. The rate of the formation of the platinum-coordinated cross-links by fresh cis Pt(II) suggests two reactions or types of reactions occur. The first is rapid and destabilizes the DNA helix, whereas the second is slow and responsible for renaturation following thermal denaturation. These results suggest that cis Pt(IV) may be activated cellularly and that cross-linking is not the primary mechanism of action of the tumor-inhibitory platinum compounds.", "contents": "Renaturation effects of cis and trans platinum II and IV compounds on calf thymus deoxyribonucleic acid. The effects of cis dichlorodiammine platinum [cis Pt(II)], trans dichlorodiammine platinum (trans Pt(II)], cis tetrachlorodiammine platinum [cis Pt(IV)], trans tetrachlorodiammine platinum [trans Pt(IV)], and ethylenediaminedichloride platinum [Pt(II)en] on the absorption spectra, and thermal hyper- and hypochromicity of calf thymus DNA were investigated. Platinum-induced renaturation was studied as one parameter of interstrand cross-linking. Based on a DNA cross-linking hypothesis, the tumor-inhibitory platinum compounds cis Pt(II), cis Pt(IV) and Pt(II)en would be expected to induce renaturation following thermal denaturation, whereas the ineffective drugs, trans Pt(II) and trans Pt(IV) would not. All five bind to DNA in such a way as to induce renaturation. However, cis Pt(IV) requires at least a 3- to 4-fold longer incubation time than is required by the other compounds to form the coordination bonds necessary for renaturation. Maximum renaturation with all compounds was observed at a molar Pt/base ratio of 0.05 except cis Pt(IV), with which it was 0.25. The rate of the formation of the platinum-coordinated cross-links by fresh cis Pt(II) suggests two reactions or types of reactions occur. The first is rapid and destabilizes the DNA helix, whereas the second is slow and responsible for renaturation following thermal denaturation. These results suggest that cis Pt(IV) may be activated cellularly and that cross-linking is not the primary mechanism of action of the tumor-inhibitory platinum compounds."}
{"id": "PMID:234802", "title": "Interactions of heme with hepatic microsomal mono-oxygenase. Effect on benzpyrene hydroxylation.", "content": "The addition of heme (1-10 muM) to liver microsomes from phenobarbital (PB)-treated and 3-methylcholanthrene (MC)-treated male rats increased the rate of benzpyrene (BP) hydroxylation by about 20-40%. On the other hand, protoporphyrin IX caused only inhibition of BP hydroxylation. There was no increase of enzymatic activity by heme when solubilized preparations of liver microsomes were used. This suggested the possibility that an apo-cytochrome P-450 was present in intact microsomes. Higher concentrations of heme inhibited BP hydroxylation by either intact or solubilized microsomes. The inhibition by heme with solubilized microsomal preparations was noncompetitive, \"mixed-type\". However, with intact microsomes, the lack of linearity, precluded the determination of the type of inhibition. To examine possible effects of heme on the binding of BP to microsomal cytochrome P-450, the spectrum elicited by the addition of BP to microsomes was obtained in the presence or absence of added heme. The addition of heme to liver microsomes produced a marked increase in the trough (419-420 nm) of the difference spectrum formed by the subsequent addition of BP. These findings would suggest that heme increased the binding of BP to microsomes. However, the possibility that BP merely displaces the bound heme of the microsomes to yield, as expected, a trough at 413-416 nm (the addition of heme to microsomes yields a peak of 413-416 nm, unpublished) cannot be ruled out. Nevertheless, independent of our understanding of the mechanism involved in the spectral interactions between heme and BP with liver microsomes it is clear that an effect at their binding site(s) must have been elicited by the presence of both compounds.", "contents": "Interactions of heme with hepatic microsomal mono-oxygenase. Effect on benzpyrene hydroxylation. The addition of heme (1-10 muM) to liver microsomes from phenobarbital (PB)-treated and 3-methylcholanthrene (MC)-treated male rats increased the rate of benzpyrene (BP) hydroxylation by about 20-40%. On the other hand, protoporphyrin IX caused only inhibition of BP hydroxylation. There was no increase of enzymatic activity by heme when solubilized preparations of liver microsomes were used. This suggested the possibility that an apo-cytochrome P-450 was present in intact microsomes. Higher concentrations of heme inhibited BP hydroxylation by either intact or solubilized microsomes. The inhibition by heme with solubilized microsomal preparations was noncompetitive, \"mixed-type\". However, with intact microsomes, the lack of linearity, precluded the determination of the type of inhibition. To examine possible effects of heme on the binding of BP to microsomal cytochrome P-450, the spectrum elicited by the addition of BP to microsomes was obtained in the presence or absence of added heme. The addition of heme to liver microsomes produced a marked increase in the trough (419-420 nm) of the difference spectrum formed by the subsequent addition of BP. These findings would suggest that heme increased the binding of BP to microsomes. However, the possibility that BP merely displaces the bound heme of the microsomes to yield, as expected, a trough at 413-416 nm (the addition of heme to microsomes yields a peak of 413-416 nm, unpublished) cannot be ruled out. Nevertheless, independent of our understanding of the mechanism involved in the spectral interactions between heme and BP with liver microsomes it is clear that an effect at their binding site(s) must have been elicited by the presence of both compounds."}
{"id": "PMID:234803", "title": "Prior receptor occupancy as a determinant of the pressor activity of infused angiotensin II in the rat.", "content": "The pressor responsiveness to angiotensin II and norepinephrine was examined in rats before and during blockade of coverting enzyme activity with the nonapeptide SQ 20881. Responses to angiotensin II were impaired by sodium deprivation but enhanced by sodium loading or bilateral nephrectomy. During the period of converting enzyme blockade, a twofold increase in the angiotensin II pressor response was observed in the salt-restricted rats, whereas only a small change occurred in the salt-loaded rats. Infusion of the inhibitor produced a profound fall in the blood pressure of the salt-depleted rats with a relatively minor fall in the sodium-loaded rats. Norepinephrine pressor responses were slightly potentiated in the salt-restricted rats after administration of SQ 20881, but no change occurred in the salt-loaded or the nephrectomized rats. These observations support the view that the decreased angiotensin II pressor activity during salt deprivation is the result of a prior occupancy of receptor sites by endogenous hormone. Therefore, a change in the number or the affinity of receptors consequent to changes in sodium balance need not be postulated to explain the phenomenon.", "contents": "Prior receptor occupancy as a determinant of the pressor activity of infused angiotensin II in the rat. The pressor responsiveness to angiotensin II and norepinephrine was examined in rats before and during blockade of coverting enzyme activity with the nonapeptide SQ 20881. Responses to angiotensin II were impaired by sodium deprivation but enhanced by sodium loading or bilateral nephrectomy. During the period of converting enzyme blockade, a twofold increase in the angiotensin II pressor response was observed in the salt-restricted rats, whereas only a small change occurred in the salt-loaded rats. Infusion of the inhibitor produced a profound fall in the blood pressure of the salt-depleted rats with a relatively minor fall in the sodium-loaded rats. Norepinephrine pressor responses were slightly potentiated in the salt-restricted rats after administration of SQ 20881, but no change occurred in the salt-loaded or the nephrectomized rats. These observations support the view that the decreased angiotensin II pressor activity during salt deprivation is the result of a prior occupancy of receptor sites by endogenous hormone. Therefore, a change in the number or the affinity of receptors consequent to changes in sodium balance need not be postulated to explain the phenomenon."}
{"id": "PMID:234804", "title": "Increased plasma catecholamine concentrations and vas deferens norepinephrine biosynthesis in men with elevated blood pressure.", "content": "Systemic biochemical indexes of sympathetic nerve functionplasma catecholamine concentrations and serum dopamine-beta-hydroxylase activitywere correlated with regional indexesnorepinephrine concentration activities of norepinephrine biosynthetic enzymes in the vas deferens\u0101nd with blood pressures and pulse rates of 57 men at the time of vasectomy. Mean plasma catecholamine content was increased 66% and 60% in men with elevated systolic and elevated systolic and diastolic blood pressures, respectively. The norepinephrine concentration, tyrosine hydroxylase activity, and dopa decarboxylase activity in the vas deferens were increased in 12%, 26%, and 17% of the men with elevated blood pressure, respectively. Tyrosine hydroxylase and dopa decarboxylase in the men with elevated systolic blood pressure were increased 41% and 68%, respectively, compared with values in the men with normal blood pressure (P less than 0.05 and P less than 0.02). Individual plasma catecholamine content was related directly to both systolic and mean blood pressure (P less than 0.01) and to activities of vas deferens tyrosine hydroxylases (P less than 0.05) and dopa decarboxylase (P less than 0.01). There was a weak, but not significant, correlation of plasma catecholamine concentration with serum dopamine-beta-hydroxylase activity. Raised plasma catecholamine concentration in men with elevated blood pressure prior to vasectomy was associated with increased neurotransmitter biosynthesis in their vas deferens, which may indicate increased sympathetic nerve tonicity and perhaps be a factor contributing to the blood pressure elevation.", "contents": "Increased plasma catecholamine concentrations and vas deferens norepinephrine biosynthesis in men with elevated blood pressure. Systemic biochemical indexes of sympathetic nerve functionplasma catecholamine concentrations and serum dopamine-beta-hydroxylase activitywere correlated with regional indexesnorepinephrine concentration activities of norepinephrine biosynthetic enzymes in the vas deferens\u0101nd with blood pressures and pulse rates of 57 men at the time of vasectomy. Mean plasma catecholamine content was increased 66% and 60% in men with elevated systolic and elevated systolic and diastolic blood pressures, respectively. The norepinephrine concentration, tyrosine hydroxylase activity, and dopa decarboxylase activity in the vas deferens were increased in 12%, 26%, and 17% of the men with elevated blood pressure, respectively. Tyrosine hydroxylase and dopa decarboxylase in the men with elevated systolic blood pressure were increased 41% and 68%, respectively, compared with values in the men with normal blood pressure (P less than 0.05 and P less than 0.02). Individual plasma catecholamine content was related directly to both systolic and mean blood pressure (P less than 0.01) and to activities of vas deferens tyrosine hydroxylases (P less than 0.05) and dopa decarboxylase (P less than 0.01). There was a weak, but not significant, correlation of plasma catecholamine concentration with serum dopamine-beta-hydroxylase activity. Raised plasma catecholamine concentration in men with elevated blood pressure prior to vasectomy was associated with increased neurotransmitter biosynthesis in their vas deferens, which may indicate increased sympathetic nerve tonicity and perhaps be a factor contributing to the blood pressure elevation."}
{"id": "PMID:234805", "title": "Dobutamine: development of a new catecholamine to selectively increase cardiac contractility.", "content": "We systematically modified isoproterenol's chemical structure to reduce chronotropic, arrhythmogenic, and vascular side effects. Experiments on dogs showed that the resulting drug, dobutamine, had an inotropic efficacy as great as that of epinephrine due to a direct action on beta1 cardiac receptors. However, unlike epinephrine, dobutamine's effect on alpha and beta2 vascular receptors was slight. At equivalent inotropic doses, dobutamine had less than a fourth of the chronotropic effect of isoproterenol. Desmethylimipramine (DMI), which blocks the sympathetic nerve fiber uptake mechanism, had no effect on dobutamine's actions. In contrast, DMI antagonized dopamine's inotropic effect, and marked chronotropic and pressor responses occurred when we used doses of dopamine large enough to elicit a direct inotropic effect. Dobutamine increased the contractility of isolated cat papillary muscles more but the automaticity less than did isoproterenol. In ischemic dog hearts, dobutamine lacked significant arrhythmic activity, whereas dopamine, norepinephrine, and isoproterenol caused severe ectopic activity. In dogs with experimentally induced low cardiac contractility, low cardiac output, and hypotension, dobutamine produced dose-related increases in cardiac contractility and output, restored arterial blood pressure, and reduced total peripheral resistance slightly. In contrast, isoproterenol failed to restore blood pressure, had only a meager effect on cardiac contractility and output, cuased extreme tachycardia, and lowered peripheral resistance more than did dobutamine. Norepinephrine, which did not increase cardiac contractility or output as much as dobutamine, excessively elevated peripheral resistance and arterial blood pressure.", "contents": "Dobutamine: development of a new catecholamine to selectively increase cardiac contractility. We systematically modified isoproterenol's chemical structure to reduce chronotropic, arrhythmogenic, and vascular side effects. Experiments on dogs showed that the resulting drug, dobutamine, had an inotropic efficacy as great as that of epinephrine due to a direct action on beta1 cardiac receptors. However, unlike epinephrine, dobutamine's effect on alpha and beta2 vascular receptors was slight. At equivalent inotropic doses, dobutamine had less than a fourth of the chronotropic effect of isoproterenol. Desmethylimipramine (DMI), which blocks the sympathetic nerve fiber uptake mechanism, had no effect on dobutamine's actions. In contrast, DMI antagonized dopamine's inotropic effect, and marked chronotropic and pressor responses occurred when we used doses of dopamine large enough to elicit a direct inotropic effect. Dobutamine increased the contractility of isolated cat papillary muscles more but the automaticity less than did isoproterenol. In ischemic dog hearts, dobutamine lacked significant arrhythmic activity, whereas dopamine, norepinephrine, and isoproterenol caused severe ectopic activity. In dogs with experimentally induced low cardiac contractility, low cardiac output, and hypotension, dobutamine produced dose-related increases in cardiac contractility and output, restored arterial blood pressure, and reduced total peripheral resistance slightly. In contrast, isoproterenol failed to restore blood pressure, had only a meager effect on cardiac contractility and output, cuased extreme tachycardia, and lowered peripheral resistance more than did dobutamine. Norepinephrine, which did not increase cardiac contractility or output as much as dobutamine, excessively elevated peripheral resistance and arterial blood pressure."}
{"id": "PMID:234807", "title": "Malignant hypertension resulting from deoxycorticosterone acetate and salt excess: role of renin and sodium in vascular changes.", "content": "The evolution of malignant hypertension was studied under metabolic balance conditions in 11 uninephrectomized rats given deoxycorticosterone acetate and 1% NaCl as drinking water. Changes in sodium and potassium balance were related to changes in blood pressure, plasma renin activity, hematocrit, and kidney histology. After 3-4 weeks of steadily positive sodium balance accompanied by continuously increasing blood pressure up to 185 plus or minus 19 (SE) mm Hg, periods of sodium loss accompanied by evidence of hemoconcentration were observed marking the onset of the malignant phase as defined by the development of fibrinoid necrosis in the kidney. Plasma renin activity remained markedly suppressed both at the fourth week (0.33 plus or minus 0.02 ng/ml hour-1) when the sodium balance was positive and the kidney biopsy negative and at the end of the experiment (0.35 plus or minus 0.36 ng/ml hour-1) when the sodium balance was negative and the kidney histology revealed malignant vasculitis. Infusion of the angiotensin II inhibitor 1-Sar-8-Ala-angiotensin II consistently failed to affect blood pressure, and the kidney tissue norepinephrine level was reduced (0.054 plus or minus 0.01 mug/g) compared with the control level (0.132 plus or minus 0.02 mug/g). We conclude that malignant vasculitis in this model is preceded by hypertension associated with sodium and water retention and is accompanied by negative sodium balance, decreases in body weight, falling blood pressure, and hemoconcentration without demonstrable participation of the renin-angiotensin system or the renal catecholamines.", "contents": "Malignant hypertension resulting from deoxycorticosterone acetate and salt excess: role of renin and sodium in vascular changes. The evolution of malignant hypertension was studied under metabolic balance conditions in 11 uninephrectomized rats given deoxycorticosterone acetate and 1% NaCl as drinking water. Changes in sodium and potassium balance were related to changes in blood pressure, plasma renin activity, hematocrit, and kidney histology. After 3-4 weeks of steadily positive sodium balance accompanied by continuously increasing blood pressure up to 185 plus or minus 19 (SE) mm Hg, periods of sodium loss accompanied by evidence of hemoconcentration were observed marking the onset of the malignant phase as defined by the development of fibrinoid necrosis in the kidney. Plasma renin activity remained markedly suppressed both at the fourth week (0.33 plus or minus 0.02 ng/ml hour-1) when the sodium balance was positive and the kidney biopsy negative and at the end of the experiment (0.35 plus or minus 0.36 ng/ml hour-1) when the sodium balance was negative and the kidney histology revealed malignant vasculitis. Infusion of the angiotensin II inhibitor 1-Sar-8-Ala-angiotensin II consistently failed to affect blood pressure, and the kidney tissue norepinephrine level was reduced (0.054 plus or minus 0.01 mug/g) compared with the control level (0.132 plus or minus 0.02 mug/g). We conclude that malignant vasculitis in this model is preceded by hypertension associated with sodium and water retention and is accompanied by negative sodium balance, decreases in body weight, falling blood pressure, and hemoconcentration without demonstrable participation of the renin-angiotensin system or the renal catecholamines."}
{"id": "PMID:234808", "title": "A renin inhibitor from rabbit kidney: conversion of a large inactive renin to a smaller active enzyme.", "content": "Renin in extracts of frozen rabbit kidney exists in two forms: active (molecular weight about 37,000) and inactive (molecular weight about 55,000) renin. The inactive form becomes active after exposure to pH 2.5 at 4 degrees C. If extracts are chromatographed on DEAE cellulose, the inactive renin dissociates into active renin plus a renin inhibitor (molecular weight about 13,000). The inhibitor recombines with active renin if the two are incubated together at 37 degrees C. The inhibitor is destroyed by acid treatment at pH 2.5 at 4 degrees C. We conclude that the activation of inactive renin is due to destruction of the inhibitor by acid. The inactive material may be a renin proenzyme or a storage form of active renin combined with inhibitor.", "contents": "A renin inhibitor from rabbit kidney: conversion of a large inactive renin to a smaller active enzyme. Renin in extracts of frozen rabbit kidney exists in two forms: active (molecular weight about 37,000) and inactive (molecular weight about 55,000) renin. The inactive form becomes active after exposure to pH 2.5 at 4 degrees C. If extracts are chromatographed on DEAE cellulose, the inactive renin dissociates into active renin plus a renin inhibitor (molecular weight about 13,000). The inhibitor recombines with active renin if the two are incubated together at 37 degrees C. The inhibitor is destroyed by acid treatment at pH 2.5 at 4 degrees C. We conclude that the activation of inactive renin is due to destruction of the inhibitor by acid. The inactive material may be a renin proenzyme or a storage form of active renin combined with inhibitor."}
{"id": "PMID:234809", "title": "Augmentation of myocardial digoxin concentration in hemorrhagic shock.", "content": "The effect of the shock state on myocardial digoxin uptake and plasma digoxin levels was examined in unanesthetized dogs following hemorrhage. Five minutes after intravenous administration of tritiated digoxin the myocardial digoxin content in animals with shock was greater than in normal animals in both left ventricle (LV) (165 plus or minus 15 (SD) ng/g vs 130 plus or minus 26 ng/g, P smaller than 0.02 and right ventricle (RV) (142 plus or minus 13 ng/g vs 111 plus or minus 22 ng/g. P smaller than 0.02) as was the plasma digoxin concentration (61.6 plus or minus 11.8 ng/ml vs 44.3 plus or minus 4.6 ng/ml, P smaller than 0.02). After one hour, in another group of dogs, the difference in myocardial concentration of digoxin between test and normal groups was even greater (LV: 213 plus or minus 26 ng/g vs 133 plus or minus 13 ng/g, P smaller than 0.001; RV: 171 plus or minus 9 ng/g vs 111 plus or minus 8 ng/g. P smaller than 0.001) despite lower plasma digoxin concentration in the test group (12.9 plus or minus 2.9 ng/ml vs 17.3 plus or minus 2.5 ng/ml, P smaller than 0.05). Diminished peripheral blood flow, peripheral digoxin delivery and uptake were probably responsible for the early difference in plasma digoxin levels. Resultant greater plasma concentrations of digoxin presented to the myocardium in the early phase, coupled with relative preservation of myocardial blood flow, may explain the greater myocardial uptake in animals with shock although myocardial mechanical factors may also be implicated. Augmented uptake of digoxin by the myocardium in canine hemorrhagic shock may be relevant to the altered susceptibility to glycoside action in clinical shock syndromes.", "contents": "Augmentation of myocardial digoxin concentration in hemorrhagic shock. The effect of the shock state on myocardial digoxin uptake and plasma digoxin levels was examined in unanesthetized dogs following hemorrhage. Five minutes after intravenous administration of tritiated digoxin the myocardial digoxin content in animals with shock was greater than in normal animals in both left ventricle (LV) (165 plus or minus 15 (SD) ng/g vs 130 plus or minus 26 ng/g, P smaller than 0.02 and right ventricle (RV) (142 plus or minus 13 ng/g vs 111 plus or minus 22 ng/g. P smaller than 0.02) as was the plasma digoxin concentration (61.6 plus or minus 11.8 ng/ml vs 44.3 plus or minus 4.6 ng/ml, P smaller than 0.02). After one hour, in another group of dogs, the difference in myocardial concentration of digoxin between test and normal groups was even greater (LV: 213 plus or minus 26 ng/g vs 133 plus or minus 13 ng/g, P smaller than 0.001; RV: 171 plus or minus 9 ng/g vs 111 plus or minus 8 ng/g. P smaller than 0.001) despite lower plasma digoxin concentration in the test group (12.9 plus or minus 2.9 ng/ml vs 17.3 plus or minus 2.5 ng/ml, P smaller than 0.05). Diminished peripheral blood flow, peripheral digoxin delivery and uptake were probably responsible for the early difference in plasma digoxin levels. Resultant greater plasma concentrations of digoxin presented to the myocardium in the early phase, coupled with relative preservation of myocardial blood flow, may explain the greater myocardial uptake in animals with shock although myocardial mechanical factors may also be implicated. Augmented uptake of digoxin by the myocardium in canine hemorrhagic shock may be relevant to the altered susceptibility to glycoside action in clinical shock syndromes."}
{"id": "PMID:234817", "title": "Ultramicro analysis for copper, cadmium, and zinc in human liver tissue by use of atomic absorption spectrophotometry and the heated graphite tube atomizer.", "content": "We describe a method of analysis for copper, cadmium, and zinc in a 15-mg (wet weight) sample of human liver by atomic absorption spectrophotometry.  The sample is digested with nitric acid (1.0 mol/liter), evaporated, and dilute HNO3 (10 mmol/liter) added.  The reconstituted acid mixture is injected into the graphite tube atomizer for analysis of Cu and Cd and aspirated into the air--acetylene flame for measurement of Zn.  The absorbance for each metal is suppressed with increasing pH.  NaNO3, KNO3, KCl, and NaCl (e.g.) quench the Cd absorbance in acid solutions that contain no protein, but not in the presence of protein.  Metal ions added to the predigestion human liver sample at 10 percent and 100 percent of the intrinsic metal concentrations were, respectively, 93 percent and 90 percent accounted for analytically in the case of Cu, 98 percent and 102 percent for Zn, and 101 percent and 93 percent for Cd.  Analysis of a National Bureau of Standards' Bovine Liver Standard Reference Material yielded results corresponding to 99 percent (Cu), 112 percent (Zn), and 91 percent (Cd) of the mean expected concentrations of these metals.  The between-run coefficient of variation for the bovine liver material was 6 percent for Cu, 9 percent for Zn, and 10 percent for Cd.  For 16 histologically normal samples of human liver, the mean values were: Cu, 26; Zn, 293; and Cd, 6.0 nanograms of metal per milligram dry weight, in agreement with values published previously.  The method can be easily and reliably applied to small samples of liver obtained by closed-needle biopsy.", "contents": "Ultramicro analysis for copper, cadmium, and zinc in human liver tissue by use of atomic absorption spectrophotometry and the heated graphite tube atomizer. We describe a method of analysis for copper, cadmium, and zinc in a 15-mg (wet weight) sample of human liver by atomic absorption spectrophotometry.  The sample is digested with nitric acid (1.0 mol/liter), evaporated, and dilute HNO3 (10 mmol/liter) added.  The reconstituted acid mixture is injected into the graphite tube atomizer for analysis of Cu and Cd and aspirated into the air--acetylene flame for measurement of Zn.  The absorbance for each metal is suppressed with increasing pH.  NaNO3, KNO3, KCl, and NaCl (e.g.) quench the Cd absorbance in acid solutions that contain no protein, but not in the presence of protein.  Metal ions added to the predigestion human liver sample at 10 percent and 100 percent of the intrinsic metal concentrations were, respectively, 93 percent and 90 percent accounted for analytically in the case of Cu, 98 percent and 102 percent for Zn, and 101 percent and 93 percent for Cd.  Analysis of a National Bureau of Standards' Bovine Liver Standard Reference Material yielded results corresponding to 99 percent (Cu), 112 percent (Zn), and 91 percent (Cd) of the mean expected concentrations of these metals.  The between-run coefficient of variation for the bovine liver material was 6 percent for Cu, 9 percent for Zn, and 10 percent for Cd.  For 16 histologically normal samples of human liver, the mean values were: Cu, 26; Zn, 293; and Cd, 6.0 nanograms of metal per milligram dry weight, in agreement with values published previously.  The method can be easily and reliably applied to small samples of liver obtained by closed-needle biopsy."}
{"id": "PMID:234818", "title": "Determination of serum copper by atomic absorption, with use of the graphite cuvette.", "content": "We have established and evaluated a flameless graphite cuvette method for copper in serum.  This atomic absorption method provides substantial improvement in sensitivity, adequate accuracy, and acceptable precision, and little sample preparation is required before the analysis.  Standard addition studies and measurements of National Bureau of Standards materials indicated that the proposed method is accurate, but that sample pH must be kept between 2 and 3 for high accuracy.  Cations and anions that frequently are present in protein-containing samples do not interfere significantly.  Sample cross contamination in the syringe must be carefully avoided.  Finally, when results for more than 100 patients' sera by this method were compared to those obtained by flame atomic absorption for the same samples, no substantial bias or inaccuracies could be attributed to this new micro-scale method for serum copper.  Hence, this method is ideally suited for use on pediatric patients.", "contents": "Determination of serum copper by atomic absorption, with use of the graphite cuvette. We have established and evaluated a flameless graphite cuvette method for copper in serum.  This atomic absorption method provides substantial improvement in sensitivity, adequate accuracy, and acceptable precision, and little sample preparation is required before the analysis.  Standard addition studies and measurements of National Bureau of Standards materials indicated that the proposed method is accurate, but that sample pH must be kept between 2 and 3 for high accuracy.  Cations and anions that frequently are present in protein-containing samples do not interfere significantly.  Sample cross contamination in the syringe must be carefully avoided.  Finally, when results for more than 100 patients' sera by this method were compared to those obtained by flame atomic absorption for the same samples, no substantial bias or inaccuracies could be attributed to this new micro-scale method for serum copper.  Hence, this method is ideally suited for use on pediatric patients."}
{"id": "PMID:234819", "title": "The contribution of the kidney to the removal of a lactic acid load under normal and acidotic conditions in the conscious rat.", "content": "1. The rate of removal from the circulation of an intravenous lactic acid load has been studied in conscious rats, previously subjected either to bilateral nephrectomy or to a sham operation. 2. In rats with normal blood pH, the apparent contribution of the kidneys to removal of the lactic acid load is 30%; less than 12% of the renal contribution is attributable to urinary excretion. 3. In bilaterally nephrectomized rats made acidotic by administration of ammonium chloride, the rate of removal of a half-neutralized lacrtic acid load is progressively decreased with increasing severity of acidosis. No such effect is seen in sham-operated animals. 4. An increase in the ability of the kidney to remove lactate during acidosis compensates for approximately half of the simultaneous fall in the capacity of the remainder of the body for lactate assimilation. 5. Basal blood lactate concentrations fall in the presence of metabolic acidosis.", "contents": "The contribution of the kidney to the removal of a lactic acid load under normal and acidotic conditions in the conscious rat. 1. The rate of removal from the circulation of an intravenous lactic acid load has been studied in conscious rats, previously subjected either to bilateral nephrectomy or to a sham operation. 2. In rats with normal blood pH, the apparent contribution of the kidneys to removal of the lactic acid load is 30%; less than 12% of the renal contribution is attributable to urinary excretion. 3. In bilaterally nephrectomized rats made acidotic by administration of ammonium chloride, the rate of removal of a half-neutralized lacrtic acid load is progressively decreased with increasing severity of acidosis. No such effect is seen in sham-operated animals. 4. An increase in the ability of the kidney to remove lactate during acidosis compensates for approximately half of the simultaneous fall in the capacity of the remainder of the body for lactate assimilation. 5. Basal blood lactate concentrations fall in the presence of metabolic acidosis."}
{"id": "PMID:234820", "title": "The assessment of acid-base disturbance in man by the use of carbon dioxide titration curves.", "content": "1. Carbon dioxide titration curves were determined in vivo in dog and man at various degrees of acute non-respiratory acidaemia and alkalaemia. 2. The slope of the CO2 titration curve (delta log Pco2/delta pH) was found to increase with the severity of the acute non-respiratory alkalaemia the slope (delta log Pco2/delta pH) tended towards unity. 3. A simple scheme based on the CO2 titration curves determined in vivo has been proposed for the assessment of acute acid-base disturbances in man. 4. Carbon dioxide titration curves were also determined in vivo in patients with chronic respiratory and non-respiratory acidaemia and it was found that these curves were not significantly different from those obtained in states of acute acid-base disturbances. It is therefore suggested that the scheme described in this paper is applicable to all acid-base disturbances.", "contents": "The assessment of acid-base disturbance in man by the use of carbon dioxide titration curves. 1. Carbon dioxide titration curves were determined in vivo in dog and man at various degrees of acute non-respiratory acidaemia and alkalaemia. 2. The slope of the CO2 titration curve (delta log Pco2/delta pH) was found to increase with the severity of the acute non-respiratory alkalaemia the slope (delta log Pco2/delta pH) tended towards unity. 3. A simple scheme based on the CO2 titration curves determined in vivo has been proposed for the assessment of acute acid-base disturbances in man. 4. Carbon dioxide titration curves were also determined in vivo in patients with chronic respiratory and non-respiratory acidaemia and it was found that these curves were not significantly different from those obtained in states of acute acid-base disturbances. It is therefore suggested that the scheme described in this paper is applicable to all acid-base disturbances."}
{"id": "PMID:234821", "title": "Enhancement of the antihypertensive effect of hydrochlorothiazide in dogs after suppression of renin release by beta-adrenergic blockade.", "content": "1. Renal hypertensive dogs were treated with hydrochlorothiazide (8-2 mumol/kg or 33 mumol/kg daily for 7 days), or timolol (4-6 mumol/kg daily for 4 days), a potent beta-adrenergic blocking agent, or combinations of these drugs). Changes in mean arterial blood pressure and plasma renin activity were measured over the treatment period. 2. Neither drug significantly lowered arterial blood pressure when administered alone. Plasma renin activity, which did not change during treatment with timolol, was substantially elevated during treatment with hydrochlorothiazide. 3. When timolol was administered concomitantly with hydrochlorothiazide, plasma renin activity was suppressed and blood pressure was significantly lowered. 4. These observations suggest that compensatory activation of the renin-angiotensin system limits the antihypertensive activity of hydrochlorothiazide in renal hypertensive dogs and suppression of diuretic-induced renin release by timolol unmasks the antihypertensive effect of the diuretic.", "contents": "Enhancement of the antihypertensive effect of hydrochlorothiazide in dogs after suppression of renin release by beta-adrenergic blockade. 1. Renal hypertensive dogs were treated with hydrochlorothiazide (8-2 mumol/kg or 33 mumol/kg daily for 7 days), or timolol (4-6 mumol/kg daily for 4 days), a potent beta-adrenergic blocking agent, or combinations of these drugs). Changes in mean arterial blood pressure and plasma renin activity were measured over the treatment period. 2. Neither drug significantly lowered arterial blood pressure when administered alone. Plasma renin activity, which did not change during treatment with timolol, was substantially elevated during treatment with hydrochlorothiazide. 3. When timolol was administered concomitantly with hydrochlorothiazide, plasma renin activity was suppressed and blood pressure was significantly lowered. 4. These observations suggest that compensatory activation of the renin-angiotensin system limits the antihypertensive activity of hydrochlorothiazide in renal hypertensive dogs and suppression of diuretic-induced renin release by timolol unmasks the antihypertensive effect of the diuretic."}
{"id": "PMID:234822", "title": "Effect of single and combined infusions of angiotensin II and aldosterone on colonic potential difference, blood pressure and renal function, in patients with adrenal deficiency.", "content": "1. The effect of single and combined infusions of angiotensin and aldosterone on colonic potential difference, blood pressure and renal function was studied in two normal male subjects and four female patients with adrenal deficiency maintained only on cortisone. 2. Aldosterone had its usual effect on colonic potential difference and it was possible to show that angiotensin had a small but definte effect of its own in the absence of aldosterone. The two hormones produced a summation response when given together. 3. The effects on renal function in two normal young male subjects were similar to those known previously. The response of the patients was different and probably reflected a number of factors, such as age, sex and long-standing adrenal deficiency. 4. Although the numbers were small, both normal subjects and patients showed a significantly greater rise of blood pressure with combined infusions of angiotensin and aldosterone than with angiotensin alone. The plasma concentrations of angiotensin were similar with both types of infusion, and so increased sensitivity to angiotensin in the presence of aldosterone is postulated.", "contents": "Effect of single and combined infusions of angiotensin II and aldosterone on colonic potential difference, blood pressure and renal function, in patients with adrenal deficiency. 1. The effect of single and combined infusions of angiotensin and aldosterone on colonic potential difference, blood pressure and renal function was studied in two normal male subjects and four female patients with adrenal deficiency maintained only on cortisone. 2. Aldosterone had its usual effect on colonic potential difference and it was possible to show that angiotensin had a small but definte effect of its own in the absence of aldosterone. The two hormones produced a summation response when given together. 3. The effects on renal function in two normal young male subjects were similar to those known previously. The response of the patients was different and probably reflected a number of factors, such as age, sex and long-standing adrenal deficiency. 4. Although the numbers were small, both normal subjects and patients showed a significantly greater rise of blood pressure with combined infusions of angiotensin and aldosterone than with angiotensin alone. The plasma concentrations of angiotensin were similar with both types of infusion, and so increased sensitivity to angiotensin in the presence of aldosterone is postulated."}
{"id": "PMID:234825", "title": "The use of indoramin to induce hypotension during general anaesthesia.", "content": "The alpha-blocker indoramin had only modest hypotensive action in the normotensive anaesthetised, paralysed patient undergoing major surgical intervention but had a greater effect in the hypertensive patient. The absence of deleterious cardiac effects even with intravenous doses as high as 1 mg/kg. supports previous findings as to the safety of this compound. It is possible that indoramin potentiates the hypotensive action of halothane but there is no evidence to suggest that an adverse interaction might arise when halothane is used to anaesthetise a patient receiving indoramin treatment.", "contents": "The use of indoramin to induce hypotension during general anaesthesia. The alpha-blocker indoramin had only modest hypotensive action in the normotensive anaesthetised, paralysed patient undergoing major surgical intervention but had a greater effect in the hypertensive patient. The absence of deleterious cardiac effects even with intravenous doses as high as 1 mg/kg. supports previous findings as to the safety of this compound. It is possible that indoramin potentiates the hypotensive action of halothane but there is no evidence to suggest that an adverse interaction might arise when halothane is used to anaesthetise a patient receiving indoramin treatment."}
{"id": "PMID:234828", "title": "Disposition of cyproheptadine in rats, mice, and humans and identification of a stable epoxide metabolite.", "content": "Radioactivity was excreted in the urine and feces of rats, mice, and humans after a dose of 14C-cyproheptadine. The major metabolite in rat urine was unconjugated, but the majority of radioactive materials in mouse and human urine were conjugated with glucuronic acid. Identification of the rat urinary metabolite of cyproheptadine as an epoxide was accomplished with mass spectrometry and other methods. The rat metabolite was 10.11 -epoxydesmethylcyproheptadine and accounted for about 25% of a 45-mg dose of cyproheptadine per kg. Only a small amount of this epoxide was found in mouse urine, and none was apparent in the urine of two humans who received 5 mg of the drug. Dihydrodiols, which could arise by epoxide hydrase hydrolysis of possible 10.11-epoxy metabolites, were not found in the urine of any of the species studied. The spoxide found in rat urine appears to be unusually stable to in vivo hydrolysis. Possible implications of these results in the species-selective pancreotoxicity of cyproheptadine in the rat are presented.", "contents": "Disposition of cyproheptadine in rats, mice, and humans and identification of a stable epoxide metabolite. Radioactivity was excreted in the urine and feces of rats, mice, and humans after a dose of 14C-cyproheptadine. The major metabolite in rat urine was unconjugated, but the majority of radioactive materials in mouse and human urine were conjugated with glucuronic acid. Identification of the rat urinary metabolite of cyproheptadine as an epoxide was accomplished with mass spectrometry and other methods. The rat metabolite was 10.11 -epoxydesmethylcyproheptadine and accounted for about 25% of a 45-mg dose of cyproheptadine per kg. Only a small amount of this epoxide was found in mouse urine, and none was apparent in the urine of two humans who received 5 mg of the drug. Dihydrodiols, which could arise by epoxide hydrase hydrolysis of possible 10.11-epoxy metabolites, were not found in the urine of any of the species studied. The spoxide found in rat urine appears to be unusually stable to in vivo hydrolysis. Possible implications of these results in the species-selective pancreotoxicity of cyproheptadine in the rat are presented."}
{"id": "PMID:234829", "title": "Oxisuran metabolism in the monkey.", "content": "Oxisuran metabolism was studied in the Rhesus monkey in order to assess the suitability of this species as an immunological model for man. The biotransformation pathways observed in the monkey are the same as those seen in rats and dogs. These pathways include the oxidation of oxisuran to a sulfone not found in human plasma or urine. Nevertheless, the monkey may merit immunological evaluation because the half-lives of biotransformation and elimination, although shorter than those exhibited by man, are greater than those in dogs and rats.", "contents": "Oxisuran metabolism in the monkey. Oxisuran metabolism was studied in the Rhesus monkey in order to assess the suitability of this species as an immunological model for man. The biotransformation pathways observed in the monkey are the same as those seen in rats and dogs. These pathways include the oxidation of oxisuran to a sulfone not found in human plasma or urine. Nevertheless, the monkey may merit immunological evaluation because the half-lives of biotransformation and elimination, although shorter than those exhibited by man, are greater than those in dogs and rats."}
{"id": "PMID:234831", "title": "The metabolism of 3-methyl-5-ethyl-5-phenylhydantoin (mephenytoin) to 5-ethyl-5-phenylhydantoin (Nirvanol) in mice in relation to anticonvulsant activity.", "content": "Mephenytoin (3-methyl-5-ethyl-5-phenylhydantoin) is metabolized to Nirvanol (5-ethyl-5-phenylhydantoin). Both compounds block the hind leg tonic extensor phase of the Maximal Electroshock Seizure (M.E.S.) Test in mice. The M.E.S. ED50 of mephenytoin is 42 mg/kh at 30 min and 35 mg/kg at 2 hr after ip administration. The M.E.S. ED50 for Nirvanol at 30 min and 2 hr was 23 and 30 mg/kg, respectively. Brain and plasma levels of mephenytoin and Nirvanol were determined by gas-liquid chromatography after ip administration of 40 mg of mephenytoin per kg. At 30 min the brain levels of mephenytoin and Nivanol were 19.2 and 8.1 mug/g, respectively. The brain levels of mephenytoin fell to 5.8 mug/g and those of Nirvanol rose to 18.2 mug/g at 2 hr. The total molar concentration of mephenytoin and Nirvanol, however, did not change more than 10% during the 2-hr period. Although the anticonvulsant activity of mephenytoin did not vary greatly during 2 hr after administration, the early activity is due in major part fo mephenytoin and the later activity to Nirvanol.", "contents": "The metabolism of 3-methyl-5-ethyl-5-phenylhydantoin (mephenytoin) to 5-ethyl-5-phenylhydantoin (Nirvanol) in mice in relation to anticonvulsant activity. Mephenytoin (3-methyl-5-ethyl-5-phenylhydantoin) is metabolized to Nirvanol (5-ethyl-5-phenylhydantoin). Both compounds block the hind leg tonic extensor phase of the Maximal Electroshock Seizure (M.E.S.) Test in mice. The M.E.S. ED50 of mephenytoin is 42 mg/kh at 30 min and 35 mg/kg at 2 hr after ip administration. The M.E.S. ED50 for Nirvanol at 30 min and 2 hr was 23 and 30 mg/kg, respectively. Brain and plasma levels of mephenytoin and Nirvanol were determined by gas-liquid chromatography after ip administration of 40 mg of mephenytoin per kg. At 30 min the brain levels of mephenytoin and Nivanol were 19.2 and 8.1 mug/g, respectively. The brain levels of mephenytoin fell to 5.8 mug/g and those of Nirvanol rose to 18.2 mug/g at 2 hr. The total molar concentration of mephenytoin and Nirvanol, however, did not change more than 10% during the 2-hr period. Although the anticonvulsant activity of mephenytoin did not vary greatly during 2 hr after administration, the early activity is due in major part fo mephenytoin and the later activity to Nirvanol."}
{"id": "PMID:234830", "title": "Metabolism of 1-(0-chlorophenyl)-1-(p-chlorophenyl)-2,2-dichloroethane (o,p'-DDD) in rats.", "content": "The metabolism of 14C-labeled 1-(p-chlorophenyl)-2,2-dichloroethane (o,p'-DDD) in rats was investigated. Metabolites were identified in feces and urine extracts by thin-layter chromatography (TLC), gas-liquid chromatography, and mass spectropmetry. Extracts of acidic metabolites were methylated with diazomethane for identification. Metabolites were quantitated by TLC and liquid scintillation counting. After a 100-mg oral dose to each of three rats, an average of 7.1% of the radioactivity was excreted in the urine and 87.8% in the feces within 8 days. The urine was found to contain o,p'-dichlorodiphenylacetic acid (o,p'-DDA) as well as 4-hydroxy-, 3-hydroxy-, and 3,4-dihydroxy-substituted o,p'-DDA. The serine and glycine conjugates of o,p'-DDA were also identified. In addition to the above metabolites the feces contained o,p'-DDD. 1-(o-chlorophenyl)-1-(P-chlorophenyl)-2-chloroethylene, and the aspartic acid conjugate of o,p'-DDA. The presence of aromatic mono- and dihydroxylated o,p'-DDD was also detected in feces.", "contents": "Metabolism of 1-(0-chlorophenyl)-1-(p-chlorophenyl)-2,2-dichloroethane (o,p'-DDD) in rats. The metabolism of 14C-labeled 1-(p-chlorophenyl)-2,2-dichloroethane (o,p'-DDD) in rats was investigated. Metabolites were identified in feces and urine extracts by thin-layter chromatography (TLC), gas-liquid chromatography, and mass spectropmetry. Extracts of acidic metabolites were methylated with diazomethane for identification. Metabolites were quantitated by TLC and liquid scintillation counting. After a 100-mg oral dose to each of three rats, an average of 7.1% of the radioactivity was excreted in the urine and 87.8% in the feces within 8 days. The urine was found to contain o,p'-dichlorodiphenylacetic acid (o,p'-DDA) as well as 4-hydroxy-, 3-hydroxy-, and 3,4-dihydroxy-substituted o,p'-DDA. The serine and glycine conjugates of o,p'-DDA were also identified. In addition to the above metabolites the feces contained o,p'-DDD. 1-(o-chlorophenyl)-1-(P-chlorophenyl)-2-chloroethylene, and the aspartic acid conjugate of o,p'-DDA. The presence of aromatic mono- and dihydroxylated o,p'-DDD was also detected in feces."}
{"id": "PMID:234836", "title": "[The role of laparoscopy in pulmonary disease (author's transl)].", "content": "Laparoscopy demonstrated sarcoidosis in 79 of 94 proven cases. In addition, it made it possible to assess the involvement of intraabdominal organs which cannot be judged clinically or biochemically and may not be parallel to changes in the thoracic X-ray. Extensive liver sarcoidosis was revealed in 12 and required treatment independent of other organ manifestations. Miliary exudative or cavernous pulmonary tuberculosis in 15 cases revealed gross non-specific changes in one, miliary foci of the liver surface in 13 and coarse nodular infiltration in one. In each case the visual findings were confirmed histologically in the liver biopsy, in 11 before the bacteriological results were known, which retrospectively were positive in only 9 instances. Laparoscopy is, therefore, an important and relatively sparing test, also in confirmation of pulmonary disease (sarcoidosis, certain forms of tuberculosis).", "contents": "[The role of laparoscopy in pulmonary disease (author's transl)]. Laparoscopy demonstrated sarcoidosis in 79 of 94 proven cases. In addition, it made it possible to assess the involvement of intraabdominal organs which cannot be judged clinically or biochemically and may not be parallel to changes in the thoracic X-ray. Extensive liver sarcoidosis was revealed in 12 and required treatment independent of other organ manifestations. Miliary exudative or cavernous pulmonary tuberculosis in 15 cases revealed gross non-specific changes in one, miliary foci of the liver surface in 13 and coarse nodular infiltration in one. In each case the visual findings were confirmed histologically in the liver biopsy, in 11 before the bacteriological results were known, which retrospectively were positive in only 9 instances. Laparoscopy is, therefore, an important and relatively sparing test, also in confirmation of pulmonary disease (sarcoidosis, certain forms of tuberculosis)."}
{"id": "PMID:234832", "title": "Transfer characteristics of triamterene and its analogs. Central nervous system, placenta, and kidney.", "content": "Earlier in vivo studies revealed a low concentration of triamterene in the brain of guinea pigs and baboons, and a transfer of the drug from the fetus to the mother. Additional investigations have been performed to characterize further the transport system(s) for triamterene in the central nervous system (CNS), placenta, and kidney. In guinea pigs a very low brain to free plasma concentration ratio (0.1) was achieved 3.5 min after drug administration and was maintained during 180 min of drug infusion. The cerebrospinal fluid (CSF) concentration was similar to the concentration of the drug in the brain. A higher brain to free plasma concentration ratio was gradually reached in dogs studied with nanogram per ml and microgram per ml concentrations of triamterene in CSF. Administration of triamterene to fetal and maternal sheep revealed a placental extraction (E) from fetal plasma to placenta 20 times greater than that from maternal plasma to placenta. The E from fetal plasma to placenta was unaffected by a triamterene concentration in the maternal circulation 10 times that in the fetus. These findings and studies of renal clearance support an active transfer of triamterene by the CNS, placenta, and kidney; the physiologic substrate for these systems is unknown.", "contents": "Transfer characteristics of triamterene and its analogs. Central nervous system, placenta, and kidney. Earlier in vivo studies revealed a low concentration of triamterene in the brain of guinea pigs and baboons, and a transfer of the drug from the fetus to the mother. Additional investigations have been performed to characterize further the transport system(s) for triamterene in the central nervous system (CNS), placenta, and kidney. In guinea pigs a very low brain to free plasma concentration ratio (0.1) was achieved 3.5 min after drug administration and was maintained during 180 min of drug infusion. The cerebrospinal fluid (CSF) concentration was similar to the concentration of the drug in the brain. A higher brain to free plasma concentration ratio was gradually reached in dogs studied with nanogram per ml and microgram per ml concentrations of triamterene in CSF. Administration of triamterene to fetal and maternal sheep revealed a placental extraction (E) from fetal plasma to placenta 20 times greater than that from maternal plasma to placenta. The E from fetal plasma to placenta was unaffected by a triamterene concentration in the maternal circulation 10 times that in the fetus. These findings and studies of renal clearance support an active transfer of triamterene by the CNS, placenta, and kidney; the physiologic substrate for these systems is unknown."}
{"id": "PMID:234837", "title": "[Rapidly debilitating disease with generalized lymphadenopathy, skin involvement and interstitial pulmonary infiltration (report of three cases)].", "content": "Generalized but well-circumscribed lymphadenopathy and rash-like skin changes were observed in three men, aged 58 to 75 years. There was a reticular appearance in the chest X-ray. Dyspnoea, weakness, marked weight loss, changing but marked lymphopenia, markedly increased blood-sedimentation rate, and an always negative Tine test were present in all three. Despite antibiotics, cytostatic drugs and prednisolone the disease quickly ended fatally with high fever, general debilitation and pneumonia. Post-mortem examination revealed diffuse lymphatic hyperplasia with plasma-cell infiltration in the lymph nodes, tonsils and lymphatic tissue of the intestines, and diffuse hyperplasia of the endothelial venules, together with basophilic blast cells, eosimophilic granulocytes and reticulum cells with broad nucleoli. The spleen was normal or enlarged. Spleen, lung tissue and lymphatics, the skin in the area of the small vessels, hair follicles and sweat glands contained lymphocytes, plasma cells and eosinophilic leucocytes. The spleen, if enlarged, also had focal necroses in its periarteriolar septa. In two cases electrophoresis revealed beta-globulin poorly demarkated from gamma-globulin, doubling and increase. In the third case, IgA was markedly increased with one each monoclonal IgG1 und IgA, and corresponding shift in the chi/lambda relationship in serum. Immunohistologically, lymphocytes were made up of about 20 percent IgG-containing and about 25 percent IgA-containing cells. Lymphopenia, if present, was associated with markedly reduced blast transformation of peripheral lymphocytes to phytohaemagglutinin. The granulocytes were defective (intracellular killing of Candida albicans and Staphylococcus aureus), while the nitrobluetetrazolium test was normal. There was RBC phagocytosis in the macrophages of bone marrow and in Kupffer cells of all three cases.", "contents": "[Rapidly debilitating disease with generalized lymphadenopathy, skin involvement and interstitial pulmonary infiltration (report of three cases)]. Generalized but well-circumscribed lymphadenopathy and rash-like skin changes were observed in three men, aged 58 to 75 years. There was a reticular appearance in the chest X-ray. Dyspnoea, weakness, marked weight loss, changing but marked lymphopenia, markedly increased blood-sedimentation rate, and an always negative Tine test were present in all three. Despite antibiotics, cytostatic drugs and prednisolone the disease quickly ended fatally with high fever, general debilitation and pneumonia. Post-mortem examination revealed diffuse lymphatic hyperplasia with plasma-cell infiltration in the lymph nodes, tonsils and lymphatic tissue of the intestines, and diffuse hyperplasia of the endothelial venules, together with basophilic blast cells, eosimophilic granulocytes and reticulum cells with broad nucleoli. The spleen was normal or enlarged. Spleen, lung tissue and lymphatics, the skin in the area of the small vessels, hair follicles and sweat glands contained lymphocytes, plasma cells and eosinophilic leucocytes. The spleen, if enlarged, also had focal necroses in its periarteriolar septa. In two cases electrophoresis revealed beta-globulin poorly demarkated from gamma-globulin, doubling and increase. In the third case, IgA was markedly increased with one each monoclonal IgG1 und IgA, and corresponding shift in the chi/lambda relationship in serum. Immunohistologically, lymphocytes were made up of about 20 percent IgG-containing and about 25 percent IgA-containing cells. Lymphopenia, if present, was associated with markedly reduced blast transformation of peripheral lymphocytes to phytohaemagglutinin. The granulocytes were defective (intracellular killing of Candida albicans and Staphylococcus aureus), while the nitrobluetetrazolium test was normal. There was RBC phagocytosis in the macrophages of bone marrow and in Kupffer cells of all three cases."}
{"id": "PMID:234833", "title": "Enterohepatic circulation of bis(p-chlorophenyl)acetic acid in the rat.", "content": "After intravenous administration of 14C-bis(p-chlorophenyl)acetic acid (DDA) to biliary cannulated rats, 97% of the dose of 14C was recovered in the bile in 24 hr. When 14C-1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane (DDT) was administered orally, approximately 8% of the dose was recovered in the bile in 3 days. The metabolite in bile in each case was a conjugate of DDA, probably with glucuronic acid. Thus less than 10% of a single dose of DDT was metabolized to DDA. The biliary metabolite was shown by two methods to undergo extensive enterohepatic circulation. The role of biliary excretion and enterohepatic circulation in the elimination of DDT metabolites is discussed.", "contents": "Enterohepatic circulation of bis(p-chlorophenyl)acetic acid in the rat. After intravenous administration of 14C-bis(p-chlorophenyl)acetic acid (DDA) to biliary cannulated rats, 97% of the dose of 14C was recovered in the bile in 24 hr. When 14C-1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane (DDT) was administered orally, approximately 8% of the dose was recovered in the bile in 3 days. The metabolite in bile in each case was a conjugate of DDA, probably with glucuronic acid. Thus less than 10% of a single dose of DDT was metabolized to DDA. The biliary metabolite was shown by two methods to undergo extensive enterohepatic circulation. The role of biliary excretion and enterohepatic circulation in the elimination of DDT metabolites is discussed."}
{"id": "PMID:234838", "title": "[Consumption coagulopathy and isolated platelet deficiency in childhood septicaemia].", "content": "In a retrospective study 40 children were selected out of 53 cases of septicaemia with thrombocytopenia. They were divided into two coincidentally equally large groups of patients with consumption coagulopathy on the one side and patients with isolated thrombocytopenia without consumption coagulopathy on the other side. Both groups were of comparable age and sex distribution. Two-thirds of the children were under three months. For the differential diagnosis of both groups the activated partial thromboplastin time, the thrombotest, the factor V plasma concentration, the serum concentration of fibrin (fibrinogen) degradation products as well as control coagulation studies can be considered to have the greatest diagnostic value. The results of the study permit the following conclusions: 1. Platelet deficiency in sepsis does not prove the presence of consumption coagulopathy. 2. Consumption coagulopathy and isolated thrombocytopenia differ statistically significantly according to the bacteria cultured from the blood, the circulatory state and the pH of the blood. 3. The finding of thrombocytopenia in a patient with shock, acidosis and gramnegative septicaemia justify the suspicion of consumption coagulopathy.", "contents": "[Consumption coagulopathy and isolated platelet deficiency in childhood septicaemia]. In a retrospective study 40 children were selected out of 53 cases of septicaemia with thrombocytopenia. They were divided into two coincidentally equally large groups of patients with consumption coagulopathy on the one side and patients with isolated thrombocytopenia without consumption coagulopathy on the other side. Both groups were of comparable age and sex distribution. Two-thirds of the children were under three months. For the differential diagnosis of both groups the activated partial thromboplastin time, the thrombotest, the factor V plasma concentration, the serum concentration of fibrin (fibrinogen) degradation products as well as control coagulation studies can be considered to have the greatest diagnostic value. The results of the study permit the following conclusions: 1. Platelet deficiency in sepsis does not prove the presence of consumption coagulopathy. 2. Consumption coagulopathy and isolated thrombocytopenia differ statistically significantly according to the bacteria cultured from the blood, the circulatory state and the pH of the blood. 3. The finding of thrombocytopenia in a patient with shock, acidosis and gramnegative septicaemia justify the suspicion of consumption coagulopathy."}
{"id": "PMID:234834", "title": "Correlation of aryl hydrocarbon hydroxylase activity of human lymphocyte cultures and plasma elimination rates for antipyrine and phenylbutazone.", "content": "A high correlation was observed between the aryl hydrocarbon hydroxylase activities in short-term lymphocyte cultures of 23 individuals and their plasma half-lives of antipyrine and phenylbutazone. Individuals with low inducibility of aryl hydrocarbon hydroxylase activities had very long plasma half-lives of antipyrine and phenylbutazone, whereas subjects with high inducibility of aryl hydrocarbon hydroxylase activites had relatively short plasma half-lives. Individuals with intermediate aryl hydrocarbon hydroxylase activities displayed intermediate half-lives for both drugs. The observed correlation indicates determinants which are common to the elimination of antipyrine or phenylbutazone, and aryl hydrocarbon hydroxylase metabolism of hydrocarbons. The differences in rates of drug elimination are probably due to genetic differences and may have pharmacological and therapeutic  significance.", "contents": "Correlation of aryl hydrocarbon hydroxylase activity of human lymphocyte cultures and plasma elimination rates for antipyrine and phenylbutazone. A high correlation was observed between the aryl hydrocarbon hydroxylase activities in short-term lymphocyte cultures of 23 individuals and their plasma half-lives of antipyrine and phenylbutazone. Individuals with low inducibility of aryl hydrocarbon hydroxylase activities had very long plasma half-lives of antipyrine and phenylbutazone, whereas subjects with high inducibility of aryl hydrocarbon hydroxylase activites had relatively short plasma half-lives. Individuals with intermediate aryl hydrocarbon hydroxylase activities displayed intermediate half-lives for both drugs. The observed correlation indicates determinants which are common to the elimination of antipyrine or phenylbutazone, and aryl hydrocarbon hydroxylase metabolism of hydrocarbons. The differences in rates of drug elimination are probably due to genetic differences and may have pharmacological and therapeutic  significance."}
{"id": "PMID:234835", "title": "In vitro studies on irreversible binding of halothane metabolite to microsomes.", "content": "Incubation of rat liver microsomal suspensions with [14C] halothane resulted in the binding of a metabolite of halothane to microsomal phospholipids and, to a lesser extent, to microsomal proteins. The binding was inhibited by carbon monoxide, required NADPH, and was greatly enhanced under anaerobic conditions. The binding to lipids occurred only to phospholipids, particularly those with characteristics of phosphatidylcholine and phosphatidylethanolamine. The binding was dependent on the time of incubation as well as on the amount of microsomes present.", "contents": "In vitro studies on irreversible binding of halothane metabolite to microsomes. Incubation of rat liver microsomal suspensions with [14C] halothane resulted in the binding of a metabolite of halothane to microsomal phospholipids and, to a lesser extent, to microsomal proteins. The binding was inhibited by carbon monoxide, required NADPH, and was greatly enhanced under anaerobic conditions. The binding to lipids occurred only to phospholipids, particularly those with characteristics of phosphatidylcholine and phosphatidylethanolamine. The binding was dependent on the time of incubation as well as on the amount of microsomes present."}
{"id": "PMID:234839", "title": "[Cellular immunity in actively conditioned recipients of renal allotransplants (author's transl)].", "content": "The presence of circulating \"killer\" cells was demonstrated in actively \"conditioned\" rats with permanently accepted renal allotransplants. Immunocompetant cells of these animals were able to develop a normal graft-versus-host reaction 100 and 200 days after the transplantation. The ability of these recipients simultaneously to accept secondary donor-specific skin transplants without demonstrable immunological rejection is compatible with the concept that the cytotoxic potential of these cells in vivo is inhibited by enhancing antibodies.", "contents": "[Cellular immunity in actively conditioned recipients of renal allotransplants (author's transl)]. The presence of circulating \"killer\" cells was demonstrated in actively \"conditioned\" rats with permanently accepted renal allotransplants. Immunocompetant cells of these animals were able to develop a normal graft-versus-host reaction 100 and 200 days after the transplantation. The ability of these recipients simultaneously to accept secondary donor-specific skin transplants without demonstrable immunological rejection is compatible with the concept that the cytotoxic potential of these cells in vivo is inhibited by enhancing antibodies."}
{"id": "PMID:234840", "title": "[Cardiac side-effects of bencyclan].", "content": "Bencyclan (Fludilat), used therapeutically as a vasodilator drug, exerts a distinct negative inotropic and chronotropic action on myocardium, in contrast to papaverine.  It prolongs the functional refractory period in the isolated heart preparation.  In isolated myocardial mitochondria it decreases the velocity of oxidative phosphorylation and the rate of calcium uptake.  These results indicate that heart function should be checked if bencyclan is applied at high dosage, especially if other cardio-depressive substances such as narcotics, antidepressive and antiarrhythmic agents as well as beta-adrenergic blockers are used at the same time.  On the other hand, the results suggest that bencyclan should be tested for possible use in the treatment of ischaemic heart disease as well as ventricular and supraventricular tachycardia.", "contents": "[Cardiac side-effects of bencyclan]. Bencyclan (Fludilat), used therapeutically as a vasodilator drug, exerts a distinct negative inotropic and chronotropic action on myocardium, in contrast to papaverine.  It prolongs the functional refractory period in the isolated heart preparation.  In isolated myocardial mitochondria it decreases the velocity of oxidative phosphorylation and the rate of calcium uptake.  These results indicate that heart function should be checked if bencyclan is applied at high dosage, especially if other cardio-depressive substances such as narcotics, antidepressive and antiarrhythmic agents as well as beta-adrenergic blockers are used at the same time.  On the other hand, the results suggest that bencyclan should be tested for possible use in the treatment of ischaemic heart disease as well as ventricular and supraventricular tachycardia."}
{"id": "PMID:234842", "title": "Cardiac output in the conscious and anaesthetised horse.", "content": "Cardiac output in the horse was measured before and at predetermined times during 2-hour periods of thiopentone-halothane and thiopentone-diethyl ether anaesthesia. Left ventricular stroke volume was decreased to a similar extent during anaesthesia with each volatile agent, but a greater reduction in cardiac output occurred during halothane anaesthesia. This finding reflected the differing effects of halothane and ether on heart rate, a slight bradycardia occurring with the former agent while ether produced a small degree of tachycardia. The latter effect was attributed to enhanced sympathoadrenal activity. Changes in cardiac output and stroke volume were considered in relation to other factors, including arterial blood pH and tensions of oxygen and carbon dioxide. Positive correlations between some of these variables and cardiac function were established. With both volatile agents the reductions in stroke volume and cardiac output were related to the duration of anaesthesia, being greatest during the early stages. Possible reasons for the tendency of stroke volume and cardiac output to return towards control levels are discussed.", "contents": "Cardiac output in the conscious and anaesthetised horse. Cardiac output in the horse was measured before and at predetermined times during 2-hour periods of thiopentone-halothane and thiopentone-diethyl ether anaesthesia. Left ventricular stroke volume was decreased to a similar extent during anaesthesia with each volatile agent, but a greater reduction in cardiac output occurred during halothane anaesthesia. This finding reflected the differing effects of halothane and ether on heart rate, a slight bradycardia occurring with the former agent while ether produced a small degree of tachycardia. The latter effect was attributed to enhanced sympathoadrenal activity. Changes in cardiac output and stroke volume were considered in relation to other factors, including arterial blood pH and tensions of oxygen and carbon dioxide. Positive correlations between some of these variables and cardiac function were established. With both volatile agents the reductions in stroke volume and cardiac output were related to the duration of anaesthesia, being greatest during the early stages. Possible reasons for the tendency of stroke volume and cardiac output to return towards control levels are discussed."}
{"id": "PMID:234843", "title": "The effect of exercise on blood metabolite levels in the horse.", "content": "The effects of exercise of different intensities on blood concentrations of glucose, lactate, pyruvate, free fatty acids and glycerol were studied in a group of clinically normal horses. Blood lactate, pyruvate and lactate/pyruvate ratio increased during exercise, particularly during galloping. These changes occurred within the first 12-15 seconds of exercise indicating that anaerobic metabolic pathways are brought into use very quickly in the strenuously exercising horse. Since blood glycerol levels were significantly increased during exercise body lipids were also mobilised. At the same time, free fatty acid levels increased during cantering but decreased during galloping indicating increased fat oxidation during strenuous exercise. It was concluded that both lipids and carbohydrates are as important energy sources in the exercising horse as in other species.", "contents": "The effect of exercise on blood metabolite levels in the horse. The effects of exercise of different intensities on blood concentrations of glucose, lactate, pyruvate, free fatty acids and glycerol were studied in a group of clinically normal horses. Blood lactate, pyruvate and lactate/pyruvate ratio increased during exercise, particularly during galloping. These changes occurred within the first 12-15 seconds of exercise indicating that anaerobic metabolic pathways are brought into use very quickly in the strenuously exercising horse. Since blood glycerol levels were significantly increased during exercise body lipids were also mobilised. At the same time, free fatty acid levels increased during cantering but decreased during galloping indicating increased fat oxidation during strenuous exercise. It was concluded that both lipids and carbohydrates are as important energy sources in the exercising horse as in other species."}
{"id": "PMID:234844", "title": "Ventilation and cardiovascular studies during mechanical control of ventilation in horses.", "content": "Eleven out of 12 horses were underventilating while breathing spontaneously during halothane anaesthesia with high arterial carbon dioxide tensions. In addition, large alveolar to arterial oxygen tension gradients were found to be present. Mechanically, controlled ventilation with an intermittent positive pressure of 20-30 cm H2O reduced arterial carbon dioxide levels to normal. The alveolar to arterial oxygen gradients did not increase and in some cases decreased. These (A - a) Po2 gradients were due mainly to true shunt of the order of 30 per cent and not to ventilation perfusion inequality.", "contents": "Ventilation and cardiovascular studies during mechanical control of ventilation in horses. Eleven out of 12 horses were underventilating while breathing spontaneously during halothane anaesthesia with high arterial carbon dioxide tensions. In addition, large alveolar to arterial oxygen tension gradients were found to be present. Mechanically, controlled ventilation with an intermittent positive pressure of 20-30 cm H2O reduced arterial carbon dioxide levels to normal. The alveolar to arterial oxygen gradients did not increase and in some cases decreased. These (A - a) Po2 gradients were due mainly to true shunt of the order of 30 per cent and not to ventilation perfusion inequality."}
{"id": "PMID:234845", "title": "The effects of thioketo substitution upon uracil-adenine interactions in polyribonucleotides. Synthesis and properties of the alternating polynucleotides poly(r(A-s2U)) and poly(r(A-s2s4U)).", "content": "The polynucleotides poly[r(A-s-2U)] and poly]r(A-s2s4U)] have been synthesized and characterized by nearest-neighbour analysis, sedimentation analysis as well as spectroscopic techniques. Absorption-temperature profile and absorption-pH profile of poly[r(A-s-2U)] did not reveal a structural transition between 10 and 95 degrees C even at low ionic strength, although a variety of properties indicated a helical structure of poly[r(A-s-2U)]: remarkable hyperchromicity of the absorption spectrum, circular dichroic spectrum displaying extrema of large amplitudes, resistance against hydrolysis by ribonuclease and interaction with ethidium bromide in a manner which is characteristic of helical polynucleotides. Our results show that interactions of the type A-s-2U and A-s-2s-4U do in fact exist in helical polynucleotides. The properties of poly]r(As-2U)] furthermore demonstrate the general stabilizing effect of 2-thioketopyrimidine bases in helical polynucleotides by virtue of vertical stacking interactions with neighbouring pyrimiding and purine bases.", "contents": "The effects of thioketo substitution upon uracil-adenine interactions in polyribonucleotides. Synthesis and properties of the alternating polynucleotides poly(r(A-s2U)) and poly(r(A-s2s4U)). The polynucleotides poly[r(A-s-2U)] and poly]r(A-s2s4U)] have been synthesized and characterized by nearest-neighbour analysis, sedimentation analysis as well as spectroscopic techniques. Absorption-temperature profile and absorption-pH profile of poly[r(A-s-2U)] did not reveal a structural transition between 10 and 95 degrees C even at low ionic strength, although a variety of properties indicated a helical structure of poly[r(A-s-2U)]: remarkable hyperchromicity of the absorption spectrum, circular dichroic spectrum displaying extrema of large amplitudes, resistance against hydrolysis by ribonuclease and interaction with ethidium bromide in a manner which is characteristic of helical polynucleotides. Our results show that interactions of the type A-s-2U and A-s-2s-4U do in fact exist in helical polynucleotides. The properties of poly]r(As-2U)] furthermore demonstrate the general stabilizing effect of 2-thioketopyrimidine bases in helical polynucleotides by virtue of vertical stacking interactions with neighbouring pyrimiding and purine bases."}
{"id": "PMID:234846", "title": "3Alpha-hydroxysteroid dehydrogenase from Pseudomonas testosteroni: kinetic properties with NAD and its thionicotinamide analogue.", "content": "The kinetics of 3alpha-hydroxysteroid : NAD oxidoreductase (EC 1.1.1.50) from Pseudomonas testosteroni (ATCC 11996) have been investigated. The kinetic analysis based on initial activity measurements and product inhibition studies, indicates that the addition of substrate to the enzyme and the release of products from it, follows an obligatory order (ordered bi bi mechanism). The ability of the enzyme to utilize the thionicotinamide analogue of NAD (sNAD) as cofactor has been investigated using various 3alpha-hydroxysteroids from both the C19, C21, and C24 series. The results show that the reaction velocity with sNAD as the cofactor is generally lower than with NAD. The decrease, however, varies considerably, being negligible with some steroids such as litocholic acid and deoxycholic acid and very pronounced with other such as tetrahydrocortisol and tetrahydrocortisone. The introduction of an 11beta-hydroxy or an 11-oxo group into the steroid molecule significantly reduces the ability of the enzyme to attack the 3alpha-hydroxy group. No such effect could be seen when the 11-hydroxy group was in the alpha-position. The results also indicate that, whereas NAD can serve as cofactor for both the monomeric and the dimeric forms of the enzyme, sNAD only acts as cofactor for the monomeric form. Thus sNAD is a valuable tool for the study of the reversible, concentration-depenedent monomeric-dimeric transition of the 3alpha-hydroxysteroid dehydrogenase.", "contents": "3Alpha-hydroxysteroid dehydrogenase from Pseudomonas testosteroni: kinetic properties with NAD and its thionicotinamide analogue. The kinetics of 3alpha-hydroxysteroid : NAD oxidoreductase (EC 1.1.1.50) from Pseudomonas testosteroni (ATCC 11996) have been investigated. The kinetic analysis based on initial activity measurements and product inhibition studies, indicates that the addition of substrate to the enzyme and the release of products from it, follows an obligatory order (ordered bi bi mechanism). The ability of the enzyme to utilize the thionicotinamide analogue of NAD (sNAD) as cofactor has been investigated using various 3alpha-hydroxysteroids from both the C19, C21, and C24 series. The results show that the reaction velocity with sNAD as the cofactor is generally lower than with NAD. The decrease, however, varies considerably, being negligible with some steroids such as litocholic acid and deoxycholic acid and very pronounced with other such as tetrahydrocortisol and tetrahydrocortisone. The introduction of an 11beta-hydroxy or an 11-oxo group into the steroid molecule significantly reduces the ability of the enzyme to attack the 3alpha-hydroxy group. No such effect could be seen when the 11-hydroxy group was in the alpha-position. The results also indicate that, whereas NAD can serve as cofactor for both the monomeric and the dimeric forms of the enzyme, sNAD only acts as cofactor for the monomeric form. Thus sNAD is a valuable tool for the study of the reversible, concentration-depenedent monomeric-dimeric transition of the 3alpha-hydroxysteroid dehydrogenase."}
{"id": "PMID:234858", "title": "[Synthesis of 2,3-diazaphenothiazine. IX. Derivatives of 1- and 4-alkylamine, triazole and N-10-dialkylaminoalky 2,3-diazaphenothiazine].", "content": "Methods of synthesis are described for 10H-pyridazino[4,5-b] [1,4]benzothiazine with alkylamine groups at the 1 and 4 position, triazole derivatives of the same heterocycle containing a pentadecanoic chain and derivatives with dialkylaminoalkyl groups at N-10. The results of pharmacological and microbiological examination are reported.", "contents": "[Synthesis of 2,3-diazaphenothiazine. IX. Derivatives of 1- and 4-alkylamine, triazole and N-10-dialkylaminoalky 2,3-diazaphenothiazine]. Methods of synthesis are described for 10H-pyridazino[4,5-b] [1,4]benzothiazine with alkylamine groups at the 1 and 4 position, triazole derivatives of the same heterocycle containing a pentadecanoic chain and derivatives with dialkylaminoalkyl groups at N-10. The results of pharmacological and microbiological examination are reported."}
{"id": "PMID:234900", "title": "Effect of rising intragastric pH induced by several antacids on serum gastrin concentrations in duodenal ulcer patients and in a control group.", "content": "The interrelationship of the effects of antacids and of rising intragastric pH on serum gastrin levels was examined by comparing the effect of three antacids (Mg(OH)2Al(OH)3, and CaCO3), and their nonbuffering chloride compounds (MgCl2, AlCl3, and CaCl2), on serum gastrin and intragastric pH in duodenal ulcer patients. In the case of calcium, the effect of CaCl2 with a pH of 10, and in another group, CaCl2 with a pH of 2, was studied. In the case of magnesium, a control group was also investigated. In another group, the effect of a nonionized suspension (BaSO4) was studied in order to assess the contribution of intragastric volume. Serum gastrin was determined radioimmunologically, and pH measurements were performed in vitro using a glass electrode. Serum gastrin concentrations rose significantly whenever intragastric pH was raised. Serum gastrin also rose after MgCl2, AlCl3, and CaCl2 with a pH of 2, when intragastric pH was not significantly altered. This rise, however, was significantly smaller than after administration of the antacids, except in the MgCl2-Mg(OH)2 and in the CaCl2 pH 10-CaCO3 groups. No significant rise of serum gastrin levels was observed after BaSO4. In nonulcer subjects, gastrin response was smaller than in the duodenal ulcer patients. The results suggest that administration of nonbuffering Mg-, Al-, and Ca-chlorides leads to elevated serum gastrin levels in duodenal ulcer patients; rising intragastric pH, however, exerts an additional serum gastrin response.", "contents": "Effect of rising intragastric pH induced by several antacids on serum gastrin concentrations in duodenal ulcer patients and in a control group. The interrelationship of the effects of antacids and of rising intragastric pH on serum gastrin levels was examined by comparing the effect of three antacids (Mg(OH)2Al(OH)3, and CaCO3), and their nonbuffering chloride compounds (MgCl2, AlCl3, and CaCl2), on serum gastrin and intragastric pH in duodenal ulcer patients. In the case of calcium, the effect of CaCl2 with a pH of 10, and in another group, CaCl2 with a pH of 2, was studied. In the case of magnesium, a control group was also investigated. In another group, the effect of a nonionized suspension (BaSO4) was studied in order to assess the contribution of intragastric volume. Serum gastrin was determined radioimmunologically, and pH measurements were performed in vitro using a glass electrode. Serum gastrin concentrations rose significantly whenever intragastric pH was raised. Serum gastrin also rose after MgCl2, AlCl3, and CaCl2 with a pH of 2, when intragastric pH was not significantly altered. This rise, however, was significantly smaller than after administration of the antacids, except in the MgCl2-Mg(OH)2 and in the CaCl2 pH 10-CaCO3 groups. No significant rise of serum gastrin levels was observed after BaSO4. In nonulcer subjects, gastrin response was smaller than in the duodenal ulcer patients. The results suggest that administration of nonbuffering Mg-, Al-, and Ca-chlorides leads to elevated serum gastrin levels in duodenal ulcer patients; rising intragastric pH, however, exerts an additional serum gastrin response."}
{"id": "PMID:234901", "title": "Effect of optimum therapeutic dose of poldine on acid secretion, gastric acidity, gastric emptying, and serum gastrin concentration after a protein meal.", "content": "An oral optimum therapeutic dose of poldine was established in 5 normal subjects. Acid secretion in response to a protein meal was measured for 3 hr by continuous intragastric titration with sodium bicarbonate. Poldine 30 min before the meal reduced food-stimulated acid secretion from zero to 60% in the 5 subjects (average inhibition 32%). Poldine inhibited histamine-stimulated acid secretion to approximately the same extent. In separate experiments, gastric acidity after the meal was allowed to seek its natural level (i.e., there was notitration with bicarbonate). Poldine reduced average hydrogen concentration of the gastric contents by 85 to 50% from 1.5 to 3 hr after the meal. Since poldine did not alter the volume or the buffer content of the stomach, poldine inhibition of gastric acidity is due entirely to reduction of acid secretion and not to delayed emptying of food buffer. Poldine had no consistent effect on serum gastrin concentration after the meal when pH was maintained at a constant level by titration with bicarbonate; therefore, poldine inhibition of acid secretion is not mediated by a reduction of serum gastrin concentration.", "contents": "Effect of optimum therapeutic dose of poldine on acid secretion, gastric acidity, gastric emptying, and serum gastrin concentration after a protein meal. An oral optimum therapeutic dose of poldine was established in 5 normal subjects. Acid secretion in response to a protein meal was measured for 3 hr by continuous intragastric titration with sodium bicarbonate. Poldine 30 min before the meal reduced food-stimulated acid secretion from zero to 60% in the 5 subjects (average inhibition 32%). Poldine inhibited histamine-stimulated acid secretion to approximately the same extent. In separate experiments, gastric acidity after the meal was allowed to seek its natural level (i.e., there was notitration with bicarbonate). Poldine reduced average hydrogen concentration of the gastric contents by 85 to 50% from 1.5 to 3 hr after the meal. Since poldine did not alter the volume or the buffer content of the stomach, poldine inhibition of gastric acidity is due entirely to reduction of acid secretion and not to delayed emptying of food buffer. Poldine had no consistent effect on serum gastrin concentration after the meal when pH was maintained at a constant level by titration with bicarbonate; therefore, poldine inhibition of acid secretion is not mediated by a reduction of serum gastrin concentration."}
{"id": "PMID:234902", "title": "Effect of p-chloromercuribenzene sulfonate on gastric parietal and surface cell function in the dog.", "content": "p-Chloromercuribenzene sulfonate, a polar organic mercurial which presumably penetrates cell membranes with great difficulty, led to a profound decrease in acid recovered from exteriorized segments of dog gastric fundus stimulated by exogenous histamine. Trapping of secreted hydrogen ions by Tris buffer did not significantly reduce the back-diffusion component of apparent inhibition. Sodium-for-hydrogen exchange was close to unity before and after inhibition.", "contents": "Effect of p-chloromercuribenzene sulfonate on gastric parietal and surface cell function in the dog. p-Chloromercuribenzene sulfonate, a polar organic mercurial which presumably penetrates cell membranes with great difficulty, led to a profound decrease in acid recovered from exteriorized segments of dog gastric fundus stimulated by exogenous histamine. Trapping of secreted hydrogen ions by Tris buffer did not significantly reduce the back-diffusion component of apparent inhibition. Sodium-for-hydrogen exchange was close to unity before and after inhibition."}
{"id": "PMID:234904", "title": "Electron-microscopic study of a Mycoplasmatales virus, strain MV-Lg-pS2-L 172.", "content": "Morphology and adsorption of a globular virus, lysing Acholeplasma laidlawii were studied in ultrathin sections of plaques in a lawn of the host strain. The virus was globular, about 50 to 90 nm in diameter, with a clearly defined membrane, 6.5 to 8 nm thick. A protuberance about 25 to 35 nm long and 12 to 20 nm thick was observed on numerous virus particles. The evenly granulated, electron-optically dense content of the cells became clearer in cells affected by the viruses. Fibrillar structures of different thickness and small dense areas appeared in cells assumed to be in the preliminary stages of lysis. The interactions in the virus-host system and possible development stages of the virsu are discussed.", "contents": "Electron-microscopic study of a Mycoplasmatales virus, strain MV-Lg-pS2-L 172. Morphology and adsorption of a globular virus, lysing Acholeplasma laidlawii were studied in ultrathin sections of plaques in a lawn of the host strain. The virus was globular, about 50 to 90 nm in diameter, with a clearly defined membrane, 6.5 to 8 nm thick. A protuberance about 25 to 35 nm long and 12 to 20 nm thick was observed on numerous virus particles. The evenly granulated, electron-optically dense content of the cells became clearer in cells affected by the viruses. Fibrillar structures of different thickness and small dense areas appeared in cells assumed to be in the preliminary stages of lysis. The interactions in the virus-host system and possible development stages of the virsu are discussed."}
{"id": "PMID:234905", "title": "Studies on xylanase from Basidiomycetes. Selection of strains for the production of xylanase.", "content": "Formation of extracellular xylanase was studied in 10 strains of wood-destroying fungi belonging to Basidiomycetes during their submerged cultivation with willow sawdust. The highest enzyme activity was found in the fungus Trametes hirsuta (Wulf.) Pil\u00e1t. The effect of sources of carbon and nitrogen, cultivation time and initial pH of the cultivation solution on the formation of xylanase by the fungus Trametes hirsuta was investigated. The highest production of the enzyme was reached during cultivation  in the presence of willow sawdust, asparagine and at the initial pH of 5.0. The presence of xylanase, cellulase, mannanase and amylase as well as of beta-xylosidase, beta-glucosidase, beta-mannosidase and beta-galactosidase was demonstrated in the enzyme preparation obtained after a 10-day submerged cultivation of Trametes hirsuta under optimal conditions.", "contents": "Studies on xylanase from Basidiomycetes. Selection of strains for the production of xylanase. Formation of extracellular xylanase was studied in 10 strains of wood-destroying fungi belonging to Basidiomycetes during their submerged cultivation with willow sawdust. The highest enzyme activity was found in the fungus Trametes hirsuta (Wulf.) Pil\u00e1t. The effect of sources of carbon and nitrogen, cultivation time and initial pH of the cultivation solution on the formation of xylanase by the fungus Trametes hirsuta was investigated. The highest production of the enzyme was reached during cultivation  in the presence of willow sawdust, asparagine and at the initial pH of 5.0. The presence of xylanase, cellulase, mannanase and amylase as well as of beta-xylosidase, beta-glucosidase, beta-mannosidase and beta-galactosidase was demonstrated in the enzyme preparation obtained after a 10-day submerged cultivation of Trametes hirsuta under optimal conditions."}
{"id": "PMID:234909", "title": "Volume, adherence properties, membrane antigens and mitogen responsiveness of rabbit lymphoid cell subpopulations.", "content": "Subpopulations of rabbit spleen cells which respond to T and B mitogens, respectively, can be distinguished by sedimentation velocity in the earth's gravitational field. T cell subpopulations which differed in their responsiveness to Con A and to PHA could be identified by differences in adherence properties and by their sensitivity to complement mediated cell kill with RTLA-antiserum.", "contents": "Volume, adherence properties, membrane antigens and mitogen responsiveness of rabbit lymphoid cell subpopulations. Subpopulations of rabbit spleen cells which respond to T and B mitogens, respectively, can be distinguished by sedimentation velocity in the earth's gravitational field. T cell subpopulations which differed in their responsiveness to Con A and to PHA could be identified by differences in adherence properties and by their sensitivity to complement mediated cell kill with RTLA-antiserum."}
{"id": "PMID:234910", "title": "Assay, characterization, and localization of an enterotoxin produced by Salmonella.", "content": "An enterotoxic factor isolated from cultures of Salmonella yielded reproducible results in the suckling mouse model in contrast to other animal models. The enterotoxin appears to possess properties similar to both the heat-stable and heat-labile enterotoxins of Escherichia coli. Preliminary results indicate that the toxin is a protein, is located in the cell wall or outer-membrane fraction, and is difficult to separate from other cell wall constituents.", "contents": "Assay, characterization, and localization of an enterotoxin produced by Salmonella. An enterotoxic factor isolated from cultures of Salmonella yielded reproducible results in the suckling mouse model in contrast to other animal models. The enterotoxin appears to possess properties similar to both the heat-stable and heat-labile enterotoxins of Escherichia coli. Preliminary results indicate that the toxin is a protein, is located in the cell wall or outer-membrane fraction, and is difficult to separate from other cell wall constituents."}
{"id": "PMID:234911", "title": "Phagocytosis of Francisella tularensis by Rhesus monkey peripheral leukocytes.", "content": "Phagocytosis of Francisella tularensis by rhesus monkey peripheral neutrophils (PMN, was assessed by autoradiography, electron microscopy, and biochemical techniques. PMN, in contrast to mononuclear phagocytes, were unable to phagocytize F. tularensis in vitro in the absence of immune serum. It is postulated that in the nonimmune host the innate inability of PMN to phagocytize F. tularensis deletes one of the possible mechanisms of host defense to bacterial infection and thus permits the early dissemination of F. tularensis to intracellular sites of specific target tissues.", "contents": "Phagocytosis of Francisella tularensis by Rhesus monkey peripheral leukocytes. Phagocytosis of Francisella tularensis by rhesus monkey peripheral neutrophils (PMN, was assessed by autoradiography, electron microscopy, and biochemical techniques. PMN, in contrast to mononuclear phagocytes, were unable to phagocytize F. tularensis in vitro in the absence of immune serum. It is postulated that in the nonimmune host the innate inability of PMN to phagocytize F. tularensis deletes one of the possible mechanisms of host defense to bacterial infection and thus permits the early dissemination of F. tularensis to intracellular sites of specific target tissues."}
{"id": "PMID:234912", "title": "Pathophysiology of infectious hematopoietic necrosis virus disease in rainbow trout: hematological and blood chemical changes in moribund fish.", "content": "Infectious hematopoietic necrosis (IHN) is a rhabdoviral disease of rainbow trout (Salmo gairdneri). Trout were injected with IHNV, and various hematological and biochemical measurements of clinically ill fish were compared to uninfected controls. Infected fish had reduced corpuscular counts, hemoglobin, and packed cell volume, but normal mean corpuscular volume, mean corpuscular hemoglobulin, and mean corpuscular hemoglobin concentration. The percentage of immature erythrocytes was increased, but the percentage of leukocytes was unchanged. Differential leukocyte counts showed a significant decrease in neutrophils, increase in lymphocytes, but no change in monocytes. Unidentifiable necrobiotic cells were prevelant in blood smears and hematopoietic tissue imprints. Plasma bicarbonate, chloride, calcium, phosphorus, bilirubin, and osmolality were signigicantly reduced, but plasma glucose and anterior kidney ascorbate were unchanged. Plasma pH increased and the alpha fractions of the serum proteins were altered. No change was found in plasma enzymes, except that a LDH isozyme was significantly increased. The alkali reserve was diminished and alterations in acid-base and fluid balance occurred. Death probably resulted from a severe electrolyte and fluid imbalance caused by renal failure.", "contents": "Pathophysiology of infectious hematopoietic necrosis virus disease in rainbow trout: hematological and blood chemical changes in moribund fish. Infectious hematopoietic necrosis (IHN) is a rhabdoviral disease of rainbow trout (Salmo gairdneri). Trout were injected with IHNV, and various hematological and biochemical measurements of clinically ill fish were compared to uninfected controls. Infected fish had reduced corpuscular counts, hemoglobin, and packed cell volume, but normal mean corpuscular volume, mean corpuscular hemoglobulin, and mean corpuscular hemoglobin concentration. The percentage of immature erythrocytes was increased, but the percentage of leukocytes was unchanged. Differential leukocyte counts showed a significant decrease in neutrophils, increase in lymphocytes, but no change in monocytes. Unidentifiable necrobiotic cells were prevelant in blood smears and hematopoietic tissue imprints. Plasma bicarbonate, chloride, calcium, phosphorus, bilirubin, and osmolality were signigicantly reduced, but plasma glucose and anterior kidney ascorbate were unchanged. Plasma pH increased and the alpha fractions of the serum proteins were altered. No change was found in plasma enzymes, except that a LDH isozyme was significantly increased. The alkali reserve was diminished and alterations in acid-base and fluid balance occurred. Death probably resulted from a severe electrolyte and fluid imbalance caused by renal failure."}
{"id": "PMID:234913", "title": "Liver glutathione and glutathione reductase response of endotoxin-treated mice.", "content": "The decrease in the level of liver glutathione (GSH) in endotoxin-treated mice was in part due to formation of glutathione disulfide (GSSG). An electron-generating system (EGS) had no effect when incubated with soluble liver extracts from normal controls but resulted in recovery of GSH amounting to 25% in endotoxin-treated animals. Incubation in the absence of the EGS caused a decline of 16% in the GSH in extracts from normal animals compared with a 50% decrease in endotoxin-treated animals. Exclusion of nicotinamide adenine dinucleotide phosphate (NADP) from the EGS resulted in a slight decline in the GSH of the extract from the normal controls but 25% for the endotoxin-treated animals. Reduction of exogenous GSSG by the liver extracts required that exogenous NADP be added to ghe incubation mixtures.", "contents": "Liver glutathione and glutathione reductase response of endotoxin-treated mice. The decrease in the level of liver glutathione (GSH) in endotoxin-treated mice was in part due to formation of glutathione disulfide (GSSG). An electron-generating system (EGS) had no effect when incubated with soluble liver extracts from normal controls but resulted in recovery of GSH amounting to 25% in endotoxin-treated animals. Incubation in the absence of the EGS caused a decline of 16% in the GSH in extracts from normal animals compared with a 50% decrease in endotoxin-treated animals. Exclusion of nicotinamide adenine dinucleotide phosphate (NADP) from the EGS resulted in a slight decline in the GSH of the extract from the normal controls but 25% for the endotoxin-treated animals. Reduction of exogenous GSSG by the liver extracts required that exogenous NADP be added to ghe incubation mixtures."}
{"id": "PMID:234914", "title": "Effect of Corynebacterium acnes on interferon production in mouse peritoneal exudate cells.", "content": "Corynebacterium acnes, an organism closely related to C. parvum, has been recognized to have a striking effect on the reticuloendothelial system, as well as on both humoral and cellular immunity. In mice previously exposed to C. acnes, serum interferon levels induced by injection of Newcastle disease virus (NDV), Chikungunya virus (CV), and polyinosinic-polycytidylic acid are suppressed. When peritoneal macrophages and lymphocytes from animals exposed to C. acnes were cultivated in vitro, their capacity to produce interferon in response to NDV and CV was reduced. Furthermore, the interferon-producing capacity of these cells in tissue culture was inhibited after exposure to C. acnes to vitro. Exposure of separated populations of peritoneal macrophages and lymphocytes to C. acnes in vitro demonstrated that the interferon response to NDV by both cell types is inhibited. Peritoneal macrophages appear to be the major contributor to the interferon response in this system. Finally, this inhibitory effect was shown to occur after exposure to a purified cell wall preparation of C. acnes organisms, as well as a lipid extract of this preparation.", "contents": "Effect of Corynebacterium acnes on interferon production in mouse peritoneal exudate cells. Corynebacterium acnes, an organism closely related to C. parvum, has been recognized to have a striking effect on the reticuloendothelial system, as well as on both humoral and cellular immunity. In mice previously exposed to C. acnes, serum interferon levels induced by injection of Newcastle disease virus (NDV), Chikungunya virus (CV), and polyinosinic-polycytidylic acid are suppressed. When peritoneal macrophages and lymphocytes from animals exposed to C. acnes were cultivated in vitro, their capacity to produce interferon in response to NDV and CV was reduced. Furthermore, the interferon-producing capacity of these cells in tissue culture was inhibited after exposure to C. acnes to vitro. Exposure of separated populations of peritoneal macrophages and lymphocytes to C. acnes in vitro demonstrated that the interferon response to NDV by both cell types is inhibited. Peritoneal macrophages appear to be the major contributor to the interferon response in this system. Finally, this inhibitory effect was shown to occur after exposure to a purified cell wall preparation of C. acnes organisms, as well as a lipid extract of this preparation."}
{"id": "PMID:234915", "title": "Temporal appearance of opsonizing antibody to Francisella tularensis: detection by a radiometabolic assay.", "content": "The burst in oxidative metabolism that is mediated through activation of the hexose monophosphate shunt and accompanies particle ingestion by polymorphonuclear leukocytes was used as the indicator in an in vitro radiometabolic assay for detection of specific opsonizing antibody to Francisella tularensis. Release of 14CO2 from radiolabeled glucose was increased significantly when specific immune serum added to suspensions of monkey polymorphonuclear leukocytes and F. tularensis. With this method, opsonizing antibodies to F. tularensis were detected in monkey serum 3 days after vaccination. Significantly increased opsonic activity in these monkeys preceded the appearance of, and persisted longer than, antibody activity as determined by conventional serological techniques. In addition, sera from 11 of 12 humans that were immunized 1 month to 13 years previously and had nondiagnostic agglutinating antibody titers demonstrated significant opsonizing activity.", "contents": "Temporal appearance of opsonizing antibody to Francisella tularensis: detection by a radiometabolic assay. The burst in oxidative metabolism that is mediated through activation of the hexose monophosphate shunt and accompanies particle ingestion by polymorphonuclear leukocytes was used as the indicator in an in vitro radiometabolic assay for detection of specific opsonizing antibody to Francisella tularensis. Release of 14CO2 from radiolabeled glucose was increased significantly when specific immune serum added to suspensions of monkey polymorphonuclear leukocytes and F. tularensis. With this method, opsonizing antibodies to F. tularensis were detected in monkey serum 3 days after vaccination. Significantly increased opsonic activity in these monkeys preceded the appearance of, and persisted longer than, antibody activity as determined by conventional serological techniques. In addition, sera from 11 of 12 humans that were immunized 1 month to 13 years previously and had nondiagnostic agglutinating antibody titers demonstrated significant opsonizing activity."}
{"id": "PMID:234917", "title": "Dental treatment for handicapped adults.", "content": "Handicapped adults can be grouped into those who are mentally subnormal, those with major organic disease, those who are emotionally disturbed and those for whom local anaesthesia is unsuccessful. At the first visit the degree of handicap and the state of the mouth are assessed and a plan of treatment is formulated. In most of the patients, satisfactory conditions for operating can be achieved by the use of intravenous diazepam and local anaesthesia, though some may require a full general anaesthetic. The results of treatment of a group of 139 patients are analysed and it is shown that the average DMF score in handicapped adults is appreciably higher than in normal adults of the same age. The reason for the inability of some of these patients to seek and accept dental treatment under normal surgery conditions is discussed and it is shown that with suitable initial treatment many of them become able to accept treatment in the ordinary circumstances of a dental surgery.", "contents": "Dental treatment for handicapped adults. Handicapped adults can be grouped into those who are mentally subnormal, those with major organic disease, those who are emotionally disturbed and those for whom local anaesthesia is unsuccessful. At the first visit the degree of handicap and the state of the mouth are assessed and a plan of treatment is formulated. In most of the patients, satisfactory conditions for operating can be achieved by the use of intravenous diazepam and local anaesthesia, though some may require a full general anaesthetic. The results of treatment of a group of 139 patients are analysed and it is shown that the average DMF score in handicapped adults is appreciably higher than in normal adults of the same age. The reason for the inability of some of these patients to seek and accept dental treatment under normal surgery conditions is discussed and it is shown that with suitable initial treatment many of them become able to accept treatment in the ordinary circumstances of a dental surgery."}
{"id": "PMID:234918", "title": "The success of restorative dentistry?", "content": "Direct statistical evidence of the value of routine, periodic dental examination and treatment is lacking and inferences can only be drawn from surveys of population samples and groups of people. Except perhaps in areas of exceptionally favourable dentist: population ratios the restorative philosophy makes too high a demand on scarce professional resources for it to answer the treatment needs of populations. However, it was originally developed to benefit individual patients who sought dental care and the evidence at present suggests that it may postpone the loss of teeth. It is hypothesized that the restorative philosophy is palliative rather than remedial.", "contents": "The success of restorative dentistry? Direct statistical evidence of the value of routine, periodic dental examination and treatment is lacking and inferences can only be drawn from surveys of population samples and groups of people. Except perhaps in areas of exceptionally favourable dentist: population ratios the restorative philosophy makes too high a demand on scarce professional resources for it to answer the treatment needs of populations. However, it was originally developed to benefit individual patients who sought dental care and the evidence at present suggests that it may postpone the loss of teeth. It is hypothesized that the restorative philosophy is palliative rather than remedial."}
{"id": "PMID:234919", "title": "Cell-mediated immunity in the uremic rat.", "content": "The popliteal node assay of the graft-versus-host reaction in the inbred rat provides a sensitive measure of cell-mediated immunity. Spleen cells from uremic Lewis rats as well as normal cells cultured in uremic serum demonstrated significant immunosuppression which was proportional to the severity of the uremia.", "contents": "Cell-mediated immunity in the uremic rat. The popliteal node assay of the graft-versus-host reaction in the inbred rat provides a sensitive measure of cell-mediated immunity. Spleen cells from uremic Lewis rats as well as normal cells cultured in uremic serum demonstrated significant immunosuppression which was proportional to the severity of the uremia."}
{"id": "PMID:234920", "title": "Assay of chemotaxis by a reversible Boyden chamber eliminating cell detachment.", "content": "A modified in vitro assay for measuring chemotaxis of leucocytes is presented. A closed chamber is used in preference to an open one thus allowing reversal of the chamber during the incubation. The responding cells which at the time the chamber is turned over are inside the filter, then migrate upwards and are consequently retained on the filter by gravity. This chamber is compared with the conventional type and various parameters are examined using guinea pig eosinophils and other cell types. Loss of cells in the conventional Boyden technique is negligible for rabbit peritoneal neutrophils but is considerable for human and guinea pig neutrophils and eosinophils. This is circumvented by the proposed method; accordingly it allows more accurate quantitation in clinical and experimental work.", "contents": "Assay of chemotaxis by a reversible Boyden chamber eliminating cell detachment. A modified in vitro assay for measuring chemotaxis of leucocytes is presented. A closed chamber is used in preference to an open one thus allowing reversal of the chamber during the incubation. The responding cells which at the time the chamber is turned over are inside the filter, then migrate upwards and are consequently retained on the filter by gravity. This chamber is compared with the conventional type and various parameters are examined using guinea pig eosinophils and other cell types. Loss of cells in the conventional Boyden technique is negligible for rabbit peritoneal neutrophils but is considerable for human and guinea pig neutrophils and eosinophils. This is circumvented by the proposed method; accordingly it allows more accurate quantitation in clinical and experimental work."}
{"id": "PMID:234921", "title": "Histamine in the tissues of the marsupial Setonix brachyurus (the quokka).", "content": "Passive cutaneous anaphylactic (PCA) reactions in the marsupial Setonix brachyurus (the quokka) were completely inhibited by the histamine antagonist mepyramine maleate, but were unaffected by disodium cromoglycate or the serotonin antagonist, methysergide. Histological examination of quokka skin indicated that mast cell degranulation occurred during the PCA reaction in this marsupial and animals whose skin was relatively deficient in mast cells were poor PCA recipients. In contrast to many eutherian (placental) species, this marsupial was found to lack histamine in blood leukocytes and platelets. Also, while the peritoneal mast cells of rats and mice contain large quantities of histamine, this amine was not detected to quokka peritoneal washings, even after the induction of a peritoneal exudate or the regular intraperitoneal injection of antigen. Immunologic challenge of quokka blood or peritoneal cells did not induce the synthesis of histamine, but histamine release was elicited from sensitized quokka lung by antigenic challenge.", "contents": "Histamine in the tissues of the marsupial Setonix brachyurus (the quokka). Passive cutaneous anaphylactic (PCA) reactions in the marsupial Setonix brachyurus (the quokka) were completely inhibited by the histamine antagonist mepyramine maleate, but were unaffected by disodium cromoglycate or the serotonin antagonist, methysergide. Histological examination of quokka skin indicated that mast cell degranulation occurred during the PCA reaction in this marsupial and animals whose skin was relatively deficient in mast cells were poor PCA recipients. In contrast to many eutherian (placental) species, this marsupial was found to lack histamine in blood leukocytes and platelets. Also, while the peritoneal mast cells of rats and mice contain large quantities of histamine, this amine was not detected to quokka peritoneal washings, even after the induction of a peritoneal exudate or the regular intraperitoneal injection of antigen. Immunologic challenge of quokka blood or peritoneal cells did not induce the synthesis of histamine, but histamine release was elicited from sensitized quokka lung by antigenic challenge."}
{"id": "PMID:234924", "title": "Incidence and degree of hypoxemia after gynecological surgery.", "content": "Arterial blood gases and pH values were determined before and after performing abdominal hysterectomies in 32 women. Four to five liters of oxygen were given by nasal cannula to 15 patients, while 17 patients breathed only ambient air. Falls of arterial oxygen tension averaging 10 torrs were seen up to 30 minutes after surgery in the latter group, but no apparent hypoxemia occurred in the patients who received nasal oxygen. Postoperative mild hypoxemia present in patients undergoing pelvic surgery can be obviated by prophylactic administration of oxygen at low flows.", "contents": "Incidence and degree of hypoxemia after gynecological surgery. Arterial blood gases and pH values were determined before and after performing abdominal hysterectomies in 32 women. Four to five liters of oxygen were given by nasal cannula to 15 patients, while 17 patients breathed only ambient air. Falls of arterial oxygen tension averaging 10 torrs were seen up to 30 minutes after surgery in the latter group, but no apparent hypoxemia occurred in the patients who received nasal oxygen. Postoperative mild hypoxemia present in patients undergoing pelvic surgery can be obviated by prophylactic administration of oxygen at low flows."}
{"id": "PMID:234925", "title": "Prostaglandin-like activity in the aqueous humor following alkali burns.", "content": "Following application of 20 mul of 2 N sodium hydroxide to the rabbit cornea, the prostaglandin-like activity in the aqueous humor increased from undetectable levels to around 30 ng, per milliliter, a level which was sustained for up to 24 hours. This increase correlated with the previously reported sustained elevation of intraocular pressure following a 20 mul alkali burn. Pretreatment with aspirin or indomethacin virtually abolished the increase in intraocular pressure and elevation of prostaglandin-like activity in the aqueous humor following a 20 mul burn. Marked ocular hypotension following 50 mul and 100 mul sodium hydroxide burns correlated with very low prostaglandin-like activity in the aqueous humor. The low prostaglandin-like activity probably resulted from alkaline hydrolysis of aqueous prostaglandins and massive cellular death in iris and ciliary body tissues.", "contents": "Prostaglandin-like activity in the aqueous humor following alkali burns. Following application of 20 mul of 2 N sodium hydroxide to the rabbit cornea, the prostaglandin-like activity in the aqueous humor increased from undetectable levels to around 30 ng, per milliliter, a level which was sustained for up to 24 hours. This increase correlated with the previously reported sustained elevation of intraocular pressure following a 20 mul alkali burn. Pretreatment with aspirin or indomethacin virtually abolished the increase in intraocular pressure and elevation of prostaglandin-like activity in the aqueous humor following a 20 mul burn. Marked ocular hypotension following 50 mul and 100 mul sodium hydroxide burns correlated with very low prostaglandin-like activity in the aqueous humor. The low prostaglandin-like activity probably resulted from alkaline hydrolysis of aqueous prostaglandins and massive cellular death in iris and ciliary body tissues."}
{"id": "PMID:234926", "title": "Drugs affecting the cholinergic system in the intact mammalian eye. I. Evaluation of the miotic activity of acetylcholine-like drugs in the mouse eye.", "content": "The effect of concentration and pH on the miotic activity of five acetylcholine-like drugs were studied in the intact mouse eye. The data suggests that it is mainly the nonionized form of the drug which contributes to its miotic activity. Acetylcholine-like drugs, degradable by cholinesterases, exert their miotic activity at higher concentrations than do those which are resistant to enzymatic hydrolysis. More active acetylcholine-like drugs appear to be less sensitive to concentration changes.", "contents": "Drugs affecting the cholinergic system in the intact mammalian eye. I. Evaluation of the miotic activity of acetylcholine-like drugs in the mouse eye. The effect of concentration and pH on the miotic activity of five acetylcholine-like drugs were studied in the intact mouse eye. The data suggests that it is mainly the nonionized form of the drug which contributes to its miotic activity. Acetylcholine-like drugs, degradable by cholinesterases, exert their miotic activity at higher concentrations than do those which are resistant to enzymatic hydrolysis. More active acetylcholine-like drugs appear to be less sensitive to concentration changes."}
{"id": "PMID:234929", "title": "Evaluation of clinical disorders of acid-base balance.", "content": "An  understanding of acid-base disturbances depends on the interpretation of changes in blood pH, P-co-2, and bicarbonate concentration and a comprehension of the physiologic mechanisms that control them. The physiologic relationships between Pco-2 and bicarbonate can be visualized by means of the balance nomogram and this visualization facilitates determination of any excess or deficit for both respiratory and metabolic factors.", "contents": "Evaluation of clinical disorders of acid-base balance. An  understanding of acid-base disturbances depends on the interpretation of changes in blood pH, P-co-2, and bicarbonate concentration and a comprehension of the physiologic mechanisms that control them. The physiologic relationships between Pco-2 and bicarbonate can be visualized by means of the balance nomogram and this visualization facilitates determination of any excess or deficit for both respiratory and metabolic factors."}
{"id": "PMID:234927", "title": "The relationship between angiography, intraerythrocytic pH and hemoglobin oxygen equilibrium.", "content": "The acute effects of an injection of contrast material (Renovist) on intraerythrocytic and extracellular pH was studied at cardiac catheterization in 72 patients with congenital heart disease. A decrease in mean extracellular (plasma) pH (7.444 plus or minus .006 to 7.419 plus or minus 0.009) and an increase in mean intraerythrocytic pH (7.204 plus or minus .005 to 7.232 plus or minus .006) were observed within minutes after injection (p smaller than .01). In 17/72 patients, simultaneous measurements of oxygen affinity for hemoglobin as characterized by P50 (oxygen tension at 50% O-2 saturation) corrected to in vivo arterial pH decreased from a mean of 26.4 to 25.2 mm Hg (p smaller than .01). It is postulated that the acute increase in intraerythrocyte pH and increased affinity of hemoglobin for oxygen are due to a decrease in intracellular hydrogen ion concentration induced by the increase in plasma osmolality with subsequent shift of hemoglobin oxygen equilibrium via the Bohr effect.", "contents": "The relationship between angiography, intraerythrocytic pH and hemoglobin oxygen equilibrium. The acute effects of an injection of contrast material (Renovist) on intraerythrocytic and extracellular pH was studied at cardiac catheterization in 72 patients with congenital heart disease. A decrease in mean extracellular (plasma) pH (7.444 plus or minus .006 to 7.419 plus or minus 0.009) and an increase in mean intraerythrocytic pH (7.204 plus or minus .005 to 7.232 plus or minus .006) were observed within minutes after injection (p smaller than .01). In 17/72 patients, simultaneous measurements of oxygen affinity for hemoglobin as characterized by P50 (oxygen tension at 50% O-2 saturation) corrected to in vivo arterial pH decreased from a mean of 26.4 to 25.2 mm Hg (p smaller than .01). It is postulated that the acute increase in intraerythrocyte pH and increased affinity of hemoglobin for oxygen are due to a decrease in intracellular hydrogen ion concentration induced by the increase in plasma osmolality with subsequent shift of hemoglobin oxygen equilibrium via the Bohr effect."}
{"id": "PMID:234928", "title": "Solute excretion during intravenous urography: a comparison of sodium and methylglucamine iothalamates.", "content": "The sodium and methylglucamine salts of iothalamic acid were compared as urographic agents. The two drugs were administered intravenously to dogs at a dose of 600 mgI/kg. The outputs and concentrations of the major urinary solutes and the injected solutes were measured to define the differences in renal excretion of sodium and methylglucamine iothalamates. The action of methylglucamine as a relatively inert osmotic diuretic was reconfirmed. When sodium iothalamte was adminstered the tubular reabsorption of sodium and chloride was greater than when methylglucamine iothalamate was used. It is suggested that this reabsorption explains the advantage of sodium-linked agents over methylglucamine-linked agents in urography.", "contents": "Solute excretion during intravenous urography: a comparison of sodium and methylglucamine iothalamates. The sodium and methylglucamine salts of iothalamic acid were compared as urographic agents. The two drugs were administered intravenously to dogs at a dose of 600 mgI/kg. The outputs and concentrations of the major urinary solutes and the injected solutes were measured to define the differences in renal excretion of sodium and methylglucamine iothalamates. The action of methylglucamine as a relatively inert osmotic diuretic was reconfirmed. When sodium iothalamte was adminstered the tubular reabsorption of sodium and chloride was greater than when methylglucamine iothalamate was used. It is suggested that this reabsorption explains the advantage of sodium-linked agents over methylglucamine-linked agents in urography."}
{"id": "PMID:234934", "title": "Factor 420-dependent pyridine nucleotide-linked hydrogenase system of Methanobacterium ruminantium.", "content": "Methanobacterium ruminantium was shown to possess a nicotinamide adenine dinucleotide phosphate (NADP)-linked factor 420 (F420)-dependent hydrogenase system. This system was also shown to be present in Methanobacterium strain MOH. The hydrogenase system of M. ruminantium also links directly to F420, flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN), methyl viologen, and Fe-3 plus. It has a pH optimum of about 8 and an apparent Km for F420 of about 5 x 10-6 M at pH 8 when NADP is the electron acceptor. The F420-NADP oxidoreductase activity is inactive toward nicotinamide adenine dinucleotide (nad) and no NADPH:NAD or FADH2(FMNH2):NAD transhydrogenase system was detected. Neither crude ferredoxin nor boiled crude extract of Clostridium pasteuranum could replace F420 in the NADP-linked hydrogenase reaction of M. ruminantium. Also, neitther F420 nor a curde \"ferredoxin\" fraction from M. ruminantium extracts could substitute for ferredoxin in the pyruvate-ferredoxin oxidoreductase reaction of C. pasteurianum.", "contents": "Factor 420-dependent pyridine nucleotide-linked hydrogenase system of Methanobacterium ruminantium. Methanobacterium ruminantium was shown to possess a nicotinamide adenine dinucleotide phosphate (NADP)-linked factor 420 (F420)-dependent hydrogenase system. This system was also shown to be present in Methanobacterium strain MOH. The hydrogenase system of M. ruminantium also links directly to F420, flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN), methyl viologen, and Fe-3 plus. It has a pH optimum of about 8 and an apparent Km for F420 of about 5 x 10-6 M at pH 8 when NADP is the electron acceptor. The F420-NADP oxidoreductase activity is inactive toward nicotinamide adenine dinucleotide (nad) and no NADPH:NAD or FADH2(FMNH2):NAD transhydrogenase system was detected. Neither crude ferredoxin nor boiled crude extract of Clostridium pasteuranum could replace F420 in the NADP-linked hydrogenase reaction of M. ruminantium. Also, neitther F420 nor a curde \"ferredoxin\" fraction from M. ruminantium extracts could substitute for ferredoxin in the pyruvate-ferredoxin oxidoreductase reaction of C. pasteurianum."}
{"id": "PMID:234935", "title": "Factor 420-dependent pyridine nucleotide-linked formate metabolism of Methanobacterium ruminantium.", "content": "Methanobacterium ruminantium was shown to possess a formate dehydrogenase which is linked to factor 420 (F420) as the first low-molecular-weight or anionic electron transfer coenzyme. Reduced F420 obtained from the formate dehydrogenase can be further linked to the formation of hydrogen via the previously described F420-dependent hydrogenase reaction, thus constituting an apparently simple formate hydrogenlyase system, or to the reduction of nicotinamide adenine dinucleotide phosphate via F420:nicotinamide adenine dinucleotide phosphate oxidoreductase. The results indicate that hydrogen and formate, the only known energy sources for M. ruminantium and many other methanogenic bacteria, should be essentially equivalent as sources of electrons in the metabolism of this organism.", "contents": "Factor 420-dependent pyridine nucleotide-linked formate metabolism of Methanobacterium ruminantium. Methanobacterium ruminantium was shown to possess a formate dehydrogenase which is linked to factor 420 (F420) as the first low-molecular-weight or anionic electron transfer coenzyme. Reduced F420 obtained from the formate dehydrogenase can be further linked to the formation of hydrogen via the previously described F420-dependent hydrogenase reaction, thus constituting an apparently simple formate hydrogenlyase system, or to the reduction of nicotinamide adenine dinucleotide phosphate via F420:nicotinamide adenine dinucleotide phosphate oxidoreductase. The results indicate that hydrogen and formate, the only known energy sources for M. ruminantium and many other methanogenic bacteria, should be essentially equivalent as sources of electrons in the metabolism of this organism."}
{"id": "PMID:234936", "title": "Control of lysine biosynthesis in Bacillus subtilis: inhibition of diaminopimelate decarboxylase by lysine.", "content": "Diaminopimelate decarboxylase has been characterized in extracts of Bacillus subtilis and resolved from aspartokinases I and II. Under certain conditions, the enzyme is specifically inhibited by physiological concentrations of L-lysine, but less specificity and altered kinetics of inhibition are observed if lower ionic strengths are employed in the assay procedure. Diaminopimelate decarboxylase can be desensitized to lysine inhibition by either lowering the pH or diluting the enzyme in Tris buffer in the absence of pyridoxal phosphate. Evidence is presented to incidate that, under proper conditions, lysine inhibition involves an interaction of the amino acid with the enzyme rather than competition for available pyridoxal phosphate in the assay. Lysine, by affecting the level of meso-diaminopimelate, may thus regulate its biosynthesis through  sequential feedback inhibition. Analysis of the diaminopimelate decarboxylase of 15 revertants of mutants that had originally lacked diaminopimelate decarboxylase activity indicates that as little as 5% of the specific activity of enzyme observed in the wild-type strain is sufficient to permit normal growth rates. In the growing cell, diaminopimelate decarboxylase may therefore exist largely in an inhibited state.", "contents": "Control of lysine biosynthesis in Bacillus subtilis: inhibition of diaminopimelate decarboxylase by lysine. Diaminopimelate decarboxylase has been characterized in extracts of Bacillus subtilis and resolved from aspartokinases I and II. Under certain conditions, the enzyme is specifically inhibited by physiological concentrations of L-lysine, but less specificity and altered kinetics of inhibition are observed if lower ionic strengths are employed in the assay procedure. Diaminopimelate decarboxylase can be desensitized to lysine inhibition by either lowering the pH or diluting the enzyme in Tris buffer in the absence of pyridoxal phosphate. Evidence is presented to incidate that, under proper conditions, lysine inhibition involves an interaction of the amino acid with the enzyme rather than competition for available pyridoxal phosphate in the assay. Lysine, by affecting the level of meso-diaminopimelate, may thus regulate its biosynthesis through  sequential feedback inhibition. Analysis of the diaminopimelate decarboxylase of 15 revertants of mutants that had originally lacked diaminopimelate decarboxylase activity indicates that as little as 5% of the specific activity of enzyme observed in the wild-type strain is sufficient to permit normal growth rates. In the growing cell, diaminopimelate decarboxylase may therefore exist largely in an inhibited state."}
{"id": "PMID:234937", "title": "Metabolic function and properties of 4-hydroxyphenylacetic acid 1-hydroxylase from Pseudomonas acidovorans.", "content": "The enzyme 4-hydroxyphenylacetate, NAD(P)H:oxygen oxidoreductase (1-hydroxylating) (EC 1.14.13 ...; 4-hydroxyphenylacetate 1-monooxygenase; referred to here as 4-HPA 1-hydroxylase) was induced in Pseudomonas acidovorans when 4-hydroxyphenylacetate (4-PHA) was utilized as carbon source for growth; homogentisate and maleylacetoacetate were intermediates in the degradation of 4-HPA. A preparation of the hydroxylase that was free from homogentisate dioxygenase and could be stored at 4 C in the presence of dithioerythritol with little loss of activity was obtained by ultracentrifuging cell extracts; but when purified 18-fold by affinity chromatography the enzyme became unstable. Flavin adenine dinucleotide and Mg2+ ions were required for full activity. 4-HPA 1-hydrocylase was inhibited by KCl, which was uncompetitive with 4-HPA. Values of Ki determined for inhibitors competitive with 4-HPA were 17 muM dl-4-hydroxymandelic acid, 43 muM 3,4-dihydroxyphenylacetic acid, 87 muM 4-hydroxy-3-methylphenylacetic acid, and 440 muM 4-hydroxyphenylpropionic acid. Apparent Km values for substrates of 4-HPA 1-hydroxylase were 31 muM 4-HPA, 67 muM oxygen, 95 muM reduced nicotinamide adenine dinucleotide (NADH); AND 250 muM reduced nicotinamide adenine dinucleotide phosphate (NADPH). The same maximum velocity was given by NADH and NADPH. A chemical synthesis is described for 2-deutero-4-hydroxyphenylacetic acid. This compound was enzymatically hydroxylated with retention of half the deuterium in the homogentisic acid formed. Activity as substrate or inhibitor of 4-HPA 1-hydroxylase was shown only by those analogues of 4-HPA that possessed a hydroxyl group substituent at C-4 of the benze nucleus. A mechanism is suggested that accounts for this structural requirement and also for the observation that when 4-hydroxyphenoxyacetic acid was attacked by the enzyme, hydroquinone was formed by release of the side chain, probably as glycolic acid. Only one enantiometer of racemic 4-hydroxyhydratropic acid was attacked by 4-HPA 1-hydroxylase; the product, alpha-methylhomogentisic acid (2-(2,5-dihydroxyphenyl)-propionic acid), exhibited optical activity. This observation suggests that, during its shift from C-1 to C-2 of the nucleus, the side chain of the substrate remains bound to a site on the enzyme while a conformational change of the protein permits the necessary movement of the benzene ring.", "contents": "Metabolic function and properties of 4-hydroxyphenylacetic acid 1-hydroxylase from Pseudomonas acidovorans. The enzyme 4-hydroxyphenylacetate, NAD(P)H:oxygen oxidoreductase (1-hydroxylating) (EC 1.14.13 ...; 4-hydroxyphenylacetate 1-monooxygenase; referred to here as 4-HPA 1-hydroxylase) was induced in Pseudomonas acidovorans when 4-hydroxyphenylacetate (4-PHA) was utilized as carbon source for growth; homogentisate and maleylacetoacetate were intermediates in the degradation of 4-HPA. A preparation of the hydroxylase that was free from homogentisate dioxygenase and could be stored at 4 C in the presence of dithioerythritol with little loss of activity was obtained by ultracentrifuging cell extracts; but when purified 18-fold by affinity chromatography the enzyme became unstable. Flavin adenine dinucleotide and Mg2+ ions were required for full activity. 4-HPA 1-hydrocylase was inhibited by KCl, which was uncompetitive with 4-HPA. Values of Ki determined for inhibitors competitive with 4-HPA were 17 muM dl-4-hydroxymandelic acid, 43 muM 3,4-dihydroxyphenylacetic acid, 87 muM 4-hydroxy-3-methylphenylacetic acid, and 440 muM 4-hydroxyphenylpropionic acid. Apparent Km values for substrates of 4-HPA 1-hydroxylase were 31 muM 4-HPA, 67 muM oxygen, 95 muM reduced nicotinamide adenine dinucleotide (NADH); AND 250 muM reduced nicotinamide adenine dinucleotide phosphate (NADPH). The same maximum velocity was given by NADH and NADPH. A chemical synthesis is described for 2-deutero-4-hydroxyphenylacetic acid. This compound was enzymatically hydroxylated with retention of half the deuterium in the homogentisic acid formed. Activity as substrate or inhibitor of 4-HPA 1-hydroxylase was shown only by those analogues of 4-HPA that possessed a hydroxyl group substituent at C-4 of the benze nucleus. A mechanism is suggested that accounts for this structural requirement and also for the observation that when 4-hydroxyphenoxyacetic acid was attacked by the enzyme, hydroquinone was formed by release of the side chain, probably as glycolic acid. Only one enantiometer of racemic 4-hydroxyhydratropic acid was attacked by 4-HPA 1-hydroxylase; the product, alpha-methylhomogentisic acid (2-(2,5-dihydroxyphenyl)-propionic acid), exhibited optical activity. This observation suggests that, during its shift from C-1 to C-2 of the nucleus, the side chain of the substrate remains bound to a site on the enzyme while a conformational change of the protein permits the necessary movement of the benzene ring."}
{"id": "PMID:234938", "title": "Identification of the structural gene for glutamine synthetase in Klebsiella aerogenes.", "content": "Mutations at two sites of the Klebsiella aerogenes chromosome, unlinked by transduction with phages PW52 and P1, result in the lack of enzymatically active glutamine synthetase. A mutation in the glnB site leads to a marked decrease in the formation of an apparently normal enzyme. Some of the mutations in the glnA site lead to the production of enzymatically inactive material capable of reacting with anti-glutamine synthetase serum. The revertant of a glnA mutant was found to produce a glutamine synthetase with less activity and less stability to heat than the enzyme of the wild type. These results locate the structural gene to the production of enzymatically inactive glutamine synthetase antigen, not subject to repression by exogenously added ammonia. This observation suggests that glutamine synthetase is itself involved in the regulation of the synthesis of glutamine synthetase.", "contents": "Identification of the structural gene for glutamine synthetase in Klebsiella aerogenes. Mutations at two sites of the Klebsiella aerogenes chromosome, unlinked by transduction with phages PW52 and P1, result in the lack of enzymatically active glutamine synthetase. A mutation in the glnB site leads to a marked decrease in the formation of an apparently normal enzyme. Some of the mutations in the glnA site lead to the production of enzymatically inactive material capable of reacting with anti-glutamine synthetase serum. The revertant of a glnA mutant was found to produce a glutamine synthetase with less activity and less stability to heat than the enzyme of the wild type. These results locate the structural gene to the production of enzymatically inactive glutamine synthetase antigen, not subject to repression by exogenously added ammonia. This observation suggests that glutamine synthetase is itself involved in the regulation of the synthesis of glutamine synthetase."}
{"id": "PMID:234939", "title": "Genetic control of glutamine synthetase in Klebiella aerogenes.", "content": "Mutations at two sites, glnA and glnB, of the Klebsiella aerogenes chromosome result in the loss of glutamine synthetase. The locations of these sites on the chromosome were established by complementation by episomes of Escherichia coli and by determination of their linkage to other genetic sites by transduction with phage P1. The glnB gene is located at a position corresponding to 48 min on the Taylor map of the E. coli chromosome; it is linked to tryA, nadB, and GUA. The glnA gene is at a position corresponding to 77 min on the Taylor map and is linked to rha and metB; it is also closely linked to rbs, located in E. coli at 74 min, indicating a difference in this chromosomal region between E. coli and K. aerogenes. Mutations in the glnA site can also lead to nonrepressible synthesis of active glutamine synthetase. The examination of the fine genetic structure of glnA revealed that one such mutation is located between two mutations leading to the loss of enzymatic activity. This result, together with evidence that the structural gene for glutamine synthetase is at glnA, suggests that glutamine synthetase controls expression of its own structural gene by repression.", "contents": "Genetic control of glutamine synthetase in Klebiella aerogenes. Mutations at two sites, glnA and glnB, of the Klebsiella aerogenes chromosome result in the loss of glutamine synthetase. The locations of these sites on the chromosome were established by complementation by episomes of Escherichia coli and by determination of their linkage to other genetic sites by transduction with phage P1. The glnB gene is located at a position corresponding to 48 min on the Taylor map of the E. coli chromosome; it is linked to tryA, nadB, and GUA. The glnA gene is at a position corresponding to 77 min on the Taylor map and is linked to rha and metB; it is also closely linked to rbs, located in E. coli at 74 min, indicating a difference in this chromosomal region between E. coli and K. aerogenes. Mutations in the glnA site can also lead to nonrepressible synthesis of active glutamine synthetase. The examination of the fine genetic structure of glnA revealed that one such mutation is located between two mutations leading to the loss of enzymatic activity. This result, together with evidence that the structural gene for glutamine synthetase is at glnA, suggests that glutamine synthetase controls expression of its own structural gene by repression."}
{"id": "PMID:234940", "title": "Protoplast formation and leakage of intramembrane cell components: induction by the competence activator substance of pneumococci.", "content": "Treatment of pneumococci with activator (a protein that induces bacterial \"competence\" to absorb deoxyribonucleic acid molecules and undergo genetic transformation) can cause either protoplast formation or leakage of intracellular components to the medium depending on postincubation conditions. The leaked intracellular components include nucleoside phosphates, beta-galactosidase, deoxyribonuclease, autolysin, and hemolysin. Leakage and protoplast formation are induced by the electrophoretically pure activator, and these phenomena require the same conditions as induction of competence for genetic transformation, namely, genetic capacity for competence, protein synthesis, incorporation of choline, and the optimal pH for activation. It is suggested that the activator protein accelerates a normal process of transport (leakage) of autolysin molecules into the periplasmic space. The activity of these autolysin molecules from within would then unmask deoxyribonucleic acid binding sites located on the plasma membrane.", "contents": "Protoplast formation and leakage of intramembrane cell components: induction by the competence activator substance of pneumococci. Treatment of pneumococci with activator (a protein that induces bacterial \"competence\" to absorb deoxyribonucleic acid molecules and undergo genetic transformation) can cause either protoplast formation or leakage of intracellular components to the medium depending on postincubation conditions. The leaked intracellular components include nucleoside phosphates, beta-galactosidase, deoxyribonuclease, autolysin, and hemolysin. Leakage and protoplast formation are induced by the electrophoretically pure activator, and these phenomena require the same conditions as induction of competence for genetic transformation, namely, genetic capacity for competence, protein synthesis, incorporation of choline, and the optimal pH for activation. It is suggested that the activator protein accelerates a normal process of transport (leakage) of autolysin molecules into the periplasmic space. The activity of these autolysin molecules from within would then unmask deoxyribonucleic acid binding sites located on the plasma membrane."}
{"id": "PMID:234941", "title": "Fine structure of mesosomal involvement during Bacillus macerans sporulation.", "content": "The ultrastructure of endospore formation in Bacillus macerans ATCC 8244 is characterized by the examination of thin sections of cells grown synchronously in a defined medium. For the most part, sporulation in this organism proceeds as described in other Bacillus species. However, unusually extensive mesosomal involvement occurs during the early stages of sporulation, through the completion of engulfment. A large mesosome is associated with spore septum formation and a portion of this mesosome is included in the developing forespore. As engulfment continues, the forespore mesosome moves to the apex of the cell and participates in the completion of the double forespore membrane. This participation is morphologically similar to mesosome involvement in division and spore septation and seems to comprise a second sporal septation process. Based on this study, it is suggested that the mesosome functions to facilitate the \"fusion\" of membranes thought to occur during cell division and sporulation.", "contents": "Fine structure of mesosomal involvement during Bacillus macerans sporulation. The ultrastructure of endospore formation in Bacillus macerans ATCC 8244 is characterized by the examination of thin sections of cells grown synchronously in a defined medium. For the most part, sporulation in this organism proceeds as described in other Bacillus species. However, unusually extensive mesosomal involvement occurs during the early stages of sporulation, through the completion of engulfment. A large mesosome is associated with spore septum formation and a portion of this mesosome is included in the developing forespore. As engulfment continues, the forespore mesosome moves to the apex of the cell and participates in the completion of the double forespore membrane. This participation is morphologically similar to mesosome involvement in division and spore septation and seems to comprise a second sporal septation process. Based on this study, it is suggested that the mesosome functions to facilitate the \"fusion\" of membranes thought to occur during cell division and sporulation."}
{"id": "PMID:234942", "title": "Further evidence for a partially folded intermediate in penicillinase secretion by Bacillus licheniformis.", "content": "Protoplasis of Bacillus licheniformis 749/C (a mutant constitutive for penicillinase production) continued to synthesize and release penicillinase in hypertonic growth medium in the presence of trypsin and chymotrypsin at 25 mug each per ml. When the protoplasts were stripped of about half of their membrane-bound penicillinase by pretreatment at pH 9.5 or with a higher level of trypsin, penicillinase activity no longer increased in the presence of the proteases. This effect was immediately eliminated after addition of soybean trypsin inhibitor. These proteases do not significantly inhibit general protein synthesis. Stripped protoplasts of strain 749/C and of uninduced strain 749 (unable to synthesize penicillinase) were incubated with 50 mug of chymotrypsin per ml, and the supernatent fluids were examined immunochemically for peptides derived from the penicillinase chain. Such fargments were found only with the protoplasts capable of synthesizing penicillinase (strain 749/C). The direct detection of the products of protease degradation of a susceptible form of penicillinase provides strong evidence that, in stripped protoplasts of B. licheniformis 749/C, penicillinase synthesis continues in the presence of trypsin or chymotrypsin and that, in these modified membranes, the protease is able to act on an early form of the enzyme that has not yet attained the protease-resistant conformation characteristic of the membrane-bound and exopenicillinases. This finding is discussed in terms of the current models of penicillinase secretion.", "contents": "Further evidence for a partially folded intermediate in penicillinase secretion by Bacillus licheniformis. Protoplasis of Bacillus licheniformis 749/C (a mutant constitutive for penicillinase production) continued to synthesize and release penicillinase in hypertonic growth medium in the presence of trypsin and chymotrypsin at 25 mug each per ml. When the protoplasts were stripped of about half of their membrane-bound penicillinase by pretreatment at pH 9.5 or with a higher level of trypsin, penicillinase activity no longer increased in the presence of the proteases. This effect was immediately eliminated after addition of soybean trypsin inhibitor. These proteases do not significantly inhibit general protein synthesis. Stripped protoplasts of strain 749/C and of uninduced strain 749 (unable to synthesize penicillinase) were incubated with 50 mug of chymotrypsin per ml, and the supernatent fluids were examined immunochemically for peptides derived from the penicillinase chain. Such fargments were found only with the protoplasts capable of synthesizing penicillinase (strain 749/C). The direct detection of the products of protease degradation of a susceptible form of penicillinase provides strong evidence that, in stripped protoplasts of B. licheniformis 749/C, penicillinase synthesis continues in the presence of trypsin or chymotrypsin and that, in these modified membranes, the protease is able to act on an early form of the enzyme that has not yet attained the protease-resistant conformation characteristic of the membrane-bound and exopenicillinases. This finding is discussed in terms of the current models of penicillinase secretion."}
{"id": "PMID:234943", "title": "Halide uptake by the filamentous ascomycete Neocosmospora vasinfecta.", "content": "The uptake of Cl minus by the ascomycetes Neocosmospora vasinfecta was investigated. Intramycelial concentrations of more than 55 mM (890-fold the external concentration) were reached. Accumulation was as inorganic Cl minus and nystatin induced total loss of mycelial Cl minus without extensive protein loss, implying that Cl minus retention was not due to binding to macromolecules. Cl minus transport was largely unidirectional with efflux being low under all conditions. Uptake was temperature dependent (maximal Arrhenius activation energy of 18.0 kcal/mol) and was severely reduced by KCN, dicyclohexylcarbodiimide, and anaerobiosis. A comparison with the inhibition of oxygen uptake under the same conditions implied that Cl minus transport was not directly coupled to aerobic electron transport. Cl minus uptake was a saturatable function of the external Cl minus concentration, and apparent Km values of 6.4 times 10-6 M and 10-4 M were calculated. Of the anions tested, only Br minus effectively inhibited Cl minus uptake and I minus, NO3 minus, SO4 minus 2, HCO3 minus, and H2PO4 minus were without effect. Cl minus uptake did not require concomitant cation uptake.", "contents": "Halide uptake by the filamentous ascomycete Neocosmospora vasinfecta. The uptake of Cl minus by the ascomycetes Neocosmospora vasinfecta was investigated. Intramycelial concentrations of more than 55 mM (890-fold the external concentration) were reached. Accumulation was as inorganic Cl minus and nystatin induced total loss of mycelial Cl minus without extensive protein loss, implying that Cl minus retention was not due to binding to macromolecules. Cl minus transport was largely unidirectional with efflux being low under all conditions. Uptake was temperature dependent (maximal Arrhenius activation energy of 18.0 kcal/mol) and was severely reduced by KCN, dicyclohexylcarbodiimide, and anaerobiosis. A comparison with the inhibition of oxygen uptake under the same conditions implied that Cl minus transport was not directly coupled to aerobic electron transport. Cl minus uptake was a saturatable function of the external Cl minus concentration, and apparent Km values of 6.4 times 10-6 M and 10-4 M were calculated. Of the anions tested, only Br minus effectively inhibited Cl minus uptake and I minus, NO3 minus, SO4 minus 2, HCO3 minus, and H2PO4 minus were without effect. Cl minus uptake did not require concomitant cation uptake."}
{"id": "PMID:234944", "title": "Polyphosphate levels in nongrowing cells of Saccharomyces mellis as determined by magnesium ion and the phenomenon of \"Uberkompensation\".", "content": "Magnesium ion enhances the maximum amount of polyphosphate that resting phosphate-starved cells of Saccharomyces mellis can store by increasing the length of time the cells will continue assimilating phosphate. The divalent cation has no effect on the rate of formation of polymer. As much as 12 times more polyphosphate is formed in cells incubated in reaction mixtures containing 0.3 M MgCl2 than in the absence of Mg2+. Potassium ion also has an influence on the amount of polyphosphate that phosphate-starved cells can accumulate but the degree of stimulation is not very large. Mg2+ and K+ have no effect on polyphosphate formation or storage in phosphate-satiated cells. Apparently, then, there are two systems for polyphosphate accumulation in S. mellis. Each system is stable in nondividing cells. The one present in phosphate-starved cells seems to be repressible by growth of the organism in media containing orthophosphate. The shift from the derepressed state to the repressed state, or vice versa, occurs only in exponentially dividing cells in appropriate media with 100% of the cells in the new physiological state by the time the cell mass has doubled. It is suggested that the word to describe the phenomenon of the accumulation of higher amounts of polyphosphate in phosphate-starved cells than the steady-state level of phosphate-satiated cells be changed from \"uberkompensation\" to \"magnesium ubertriebung,\" or \"magnesium enhancement.\"", "contents": "Polyphosphate levels in nongrowing cells of Saccharomyces mellis as determined by magnesium ion and the phenomenon of \"Uberkompensation\". Magnesium ion enhances the maximum amount of polyphosphate that resting phosphate-starved cells of Saccharomyces mellis can store by increasing the length of time the cells will continue assimilating phosphate. The divalent cation has no effect on the rate of formation of polymer. As much as 12 times more polyphosphate is formed in cells incubated in reaction mixtures containing 0.3 M MgCl2 than in the absence of Mg2+. Potassium ion also has an influence on the amount of polyphosphate that phosphate-starved cells can accumulate but the degree of stimulation is not very large. Mg2+ and K+ have no effect on polyphosphate formation or storage in phosphate-satiated cells. Apparently, then, there are two systems for polyphosphate accumulation in S. mellis. Each system is stable in nondividing cells. The one present in phosphate-starved cells seems to be repressible by growth of the organism in media containing orthophosphate. The shift from the derepressed state to the repressed state, or vice versa, occurs only in exponentially dividing cells in appropriate media with 100% of the cells in the new physiological state by the time the cell mass has doubled. It is suggested that the word to describe the phenomenon of the accumulation of higher amounts of polyphosphate in phosphate-starved cells than the steady-state level of phosphate-satiated cells be changed from \"uberkompensation\" to \"magnesium ubertriebung,\" or \"magnesium enhancement.\""}
{"id": "PMID:234945", "title": "Dihydrofolate reductases from the wild type and aminopterin-resistant mutants of Diplococcus pneumoniae.", "content": "Dihydrofolate reductase from the wild type and aminopterin-resistant mutants of Diplococcus pneumoniae has been compared. Specific activity, optimum pH, Km, thermal stability, and inhibition by aminopterin are identical for both strains. Aminopterin resistance for such mutants is, therefore, not due to an alteration of the dihydrofolate reductase.", "contents": "Dihydrofolate reductases from the wild type and aminopterin-resistant mutants of Diplococcus pneumoniae. Dihydrofolate reductase from the wild type and aminopterin-resistant mutants of Diplococcus pneumoniae has been compared. Specific activity, optimum pH, Km, thermal stability, and inhibition by aminopterin are identical for both strains. Aminopterin resistance for such mutants is, therefore, not due to an alteration of the dihydrofolate reductase."}
{"id": "PMID:234946", "title": "Regulation of the L-lactase dehydrogenase from Lactobacillus casei by fructose-1,6-diphosphate and metal ions.", "content": "The lactate dehydrogenase of Lactobacillus casei, like that of streptococci, requires fructose-1,6-diphosphate (FDP) for activity. The L. casei enzyme has a much more acidic pH optimum (pH 5.5) than the streptococcal lactate dehydrogenases. This is apparently due to a marked decrease in the affinity of the enzyme for the activator with increasing pH above 5.5; the concentration of FDP required for half-maximal velocity increase nearly 1,000-fold from 0.002 mM at pH 5.5 to 1.65 mM at 6.6. Manganous ions increase the pH range of activity particularly on the alkaline side of the optimum by increasing the affinity for FDP. This pH dependent metal ion activation is not specific for Mn2+. Other divalent metals, Co2+, Cu2+, Cd2+, Ni2+, Fe2+, Fe2+, and Zn2+ but not Mg2+, will effectively substitute for Mn2+, but the pH dependence of the activation differs with the metal ion used. The enzyme is inhibited by a number of commonly used buffering ions, particularly phosphate, citrate, and tris (hydroxymethyl) aminomethane-maleate buffers, even at low buffer concentrations (0.02 M). These buffers inhibit by affecting the binding of FDP.", "contents": "Regulation of the L-lactase dehydrogenase from Lactobacillus casei by fructose-1,6-diphosphate and metal ions. The lactate dehydrogenase of Lactobacillus casei, like that of streptococci, requires fructose-1,6-diphosphate (FDP) for activity. The L. casei enzyme has a much more acidic pH optimum (pH 5.5) than the streptococcal lactate dehydrogenases. This is apparently due to a marked decrease in the affinity of the enzyme for the activator with increasing pH above 5.5; the concentration of FDP required for half-maximal velocity increase nearly 1,000-fold from 0.002 mM at pH 5.5 to 1.65 mM at 6.6. Manganous ions increase the pH range of activity particularly on the alkaline side of the optimum by increasing the affinity for FDP. This pH dependent metal ion activation is not specific for Mn2+. Other divalent metals, Co2+, Cu2+, Cd2+, Ni2+, Fe2+, Fe2+, and Zn2+ but not Mg2+, will effectively substitute for Mn2+, but the pH dependence of the activation differs with the metal ion used. The enzyme is inhibited by a number of commonly used buffering ions, particularly phosphate, citrate, and tris (hydroxymethyl) aminomethane-maleate buffers, even at low buffer concentrations (0.02 M). These buffers inhibit by affecting the binding of FDP."}
{"id": "PMID:234947", "title": "Purification and properties of gentisate 1,2-dioxygenase from Moraxella osloensis.", "content": "Gentisate:oxygen 1,2-oxidoreductase (decyclizing) (EC 1.13.11.4; gentisate 1,2-dioxygenase) from Moraxella osloensis was purified to homogeneity as shown by polyacrylamide gel electrophoresis. The enzyme has a molecular weight of about 154,000 and gives rise to subunits of molecular weight 40,000 in the presence of sodium dodecyl sulfate. Gentisate 1,2-dioxygenase showed broad substrate specificity and attacked a range of halogen- and alkyl-substituted gentisic acids. Maleylpyruvate, the product formed from gentisate, was degraded by cell extracts supplemented with reduced glutathione, but substituted maleylpyruvates were not attacked under these conditions.", "contents": "Purification and properties of gentisate 1,2-dioxygenase from Moraxella osloensis. Gentisate:oxygen 1,2-oxidoreductase (decyclizing) (EC 1.13.11.4; gentisate 1,2-dioxygenase) from Moraxella osloensis was purified to homogeneity as shown by polyacrylamide gel electrophoresis. The enzyme has a molecular weight of about 154,000 and gives rise to subunits of molecular weight 40,000 in the presence of sodium dodecyl sulfate. Gentisate 1,2-dioxygenase showed broad substrate specificity and attacked a range of halogen- and alkyl-substituted gentisic acids. Maleylpyruvate, the product formed from gentisate, was degraded by cell extracts supplemented with reduced glutathione, but substituted maleylpyruvates were not attacked under these conditions."}
{"id": "PMID:234948", "title": "Relation between reduced nicotinamide adenine dinucleotide oxidation and amino acid transport in membrane vesicles from Bacillus subtilis.", "content": "The rate of reduced nicotinamide adenine dinucleotide (NADH) oxidation by membrane vesicles from Bacillus subtilis W23 increases three- to fourfold during logarithmic growth, reaching maximal levels in early stationary phase. Initial rates of L-proline, L-alanine, and L-glutamate transport energized by NADH closely parallel the increase in NADH oxidation. In vesicles prepared at different stages of growth, a constant number of NADH molecules varying from 150 to 260 have to be oxidized to transport one molecule of amino acid. Membrane vesicles from B. subtilis aroD (strain RB163), a mutant defective in menaquinone synthesis, do not transport amino acids in the presence of NADH. Ascorbate plus phenazine methosulfate, however, energizes amino acid transport equally well as in vesicles of B. subtilis W23. NADH oxidation and NADH-driven amino acid transport can be restored instantaneously by the addition of menadione (vitamin K3).", "contents": "Relation between reduced nicotinamide adenine dinucleotide oxidation and amino acid transport in membrane vesicles from Bacillus subtilis. The rate of reduced nicotinamide adenine dinucleotide (NADH) oxidation by membrane vesicles from Bacillus subtilis W23 increases three- to fourfold during logarithmic growth, reaching maximal levels in early stationary phase. Initial rates of L-proline, L-alanine, and L-glutamate transport energized by NADH closely parallel the increase in NADH oxidation. In vesicles prepared at different stages of growth, a constant number of NADH molecules varying from 150 to 260 have to be oxidized to transport one molecule of amino acid. Membrane vesicles from B. subtilis aroD (strain RB163), a mutant defective in menaquinone synthesis, do not transport amino acids in the presence of NADH. Ascorbate plus phenazine methosulfate, however, energizes amino acid transport equally well as in vesicles of B. subtilis W23. NADH oxidation and NADH-driven amino acid transport can be restored instantaneously by the addition of menadione (vitamin K3)."}
{"id": "PMID:234949", "title": "Degradative acetolactate synthase of Bacillus subtilis: purification and properties.", "content": "A degradative acetolactate synthase (acetolactate pyruvate-lyase [carboxylating], EC 4.1.3.18) from Bacillus subtilis has been partially purified and characterized. The synthesis of the enzyme was induced by growth of cells in minimal medium plus isobutyrate or acetate. The enzyme was partially purified by ammonium sulfate fractionation, gel filtration, and hydroxyapatite chromatography. The pH optimum of the purified enzyme was 7.0 in phosphate buffer. When assayed in phosphate buffer (pH 7.0), activity was stimulated by acetate and inhibited by sulfate. When assayed in acetate buffer (pH 5.8), activity was inhibited both by sulfate and phosphate. Michaelis-Menten kinetics was observed when the enzyme was assayed in phosphate buffer (pH 6.0 or 7.0), and inhibition by sulfate was competitive and activation by acetate was noncompetitive. When assayed in acetate buffer (pH 5.8), nonlinear Lineweaver-Burk plots were obtained; inhibition by phosphate appeared to be competitive and that by sulfate was of the mixed type. The approximate molecular weight of the purified enzyme was 250,000 as determined by gel filtration.", "contents": "Degradative acetolactate synthase of Bacillus subtilis: purification and properties. A degradative acetolactate synthase (acetolactate pyruvate-lyase [carboxylating], EC 4.1.3.18) from Bacillus subtilis has been partially purified and characterized. The synthesis of the enzyme was induced by growth of cells in minimal medium plus isobutyrate or acetate. The enzyme was partially purified by ammonium sulfate fractionation, gel filtration, and hydroxyapatite chromatography. The pH optimum of the purified enzyme was 7.0 in phosphate buffer. When assayed in phosphate buffer (pH 7.0), activity was stimulated by acetate and inhibited by sulfate. When assayed in acetate buffer (pH 5.8), activity was inhibited both by sulfate and phosphate. Michaelis-Menten kinetics was observed when the enzyme was assayed in phosphate buffer (pH 6.0 or 7.0), and inhibition by sulfate was competitive and activation by acetate was noncompetitive. When assayed in acetate buffer (pH 5.8), nonlinear Lineweaver-Burk plots were obtained; inhibition by phosphate appeared to be competitive and that by sulfate was of the mixed type. The approximate molecular weight of the purified enzyme was 250,000 as determined by gel filtration."}
{"id": "PMID:234950", "title": "Purification and properties of a serine protease from Pseudomonas matophilia.", "content": "The extracellular protease of Pseudomonas maltophilia was partially purified by ammonium sulfate precipitation and chromatography on Sephadex G-75 and Bio-rex 70. Gel electrophoresis revealed minor impurities. The enzyme exhibited the following properties: (i) molecular weight, 35,000; (ii) A see article; 10.8; (iii) isoelectric point, 9.3; (iv) pH optimum, 10.0; (v)s20, w equal 3.47. The enzyme was rapidly inactivated by ethylenediaminetetracetate, but activity could be partially restored with divalent cations. Of those tested, Ca2+, Sr2+, Ba2+, Co2+, Cu2+, Mg2+, and Zn2+ were all effective. Both phenylmethylsulfonylfluoride and diisopropylfluorophosphate were powerful inhibitors of protease activity, but L-1-tosylamide-2-phenylethylchloromethyl ketone, iodoacetic acid, and iodoacetamide were without effect. The enzyme hydrolyzed the esters N-acetyl-L-tyrosine ethyl ester and alpha-N-benzoyl-L-arginine ethyl ester (BAEE) with Km values of 10.4 and 3.4 mM, respectively. The hydrolysis of BAEE was also inhibited by phenylarsonic acids. The kinetics of inhibition by m-nitrophenylarsonate were of the mixed type, and the K1 was 1.8 mM. The data followed a theoretical curve for a 1:1 enzyme-inhibitor complex with a dissociation constant of 1.8 mM. Inhibition by m-nitrophenylarsonate was pH dependent and followed a theoretical curve for the titration of a protonated group with a pKa of 7.0.", "contents": "Purification and properties of a serine protease from Pseudomonas matophilia. The extracellular protease of Pseudomonas maltophilia was partially purified by ammonium sulfate precipitation and chromatography on Sephadex G-75 and Bio-rex 70. Gel electrophoresis revealed minor impurities. The enzyme exhibited the following properties: (i) molecular weight, 35,000; (ii) A see article; 10.8; (iii) isoelectric point, 9.3; (iv) pH optimum, 10.0; (v)s20, w equal 3.47. The enzyme was rapidly inactivated by ethylenediaminetetracetate, but activity could be partially restored with divalent cations. Of those tested, Ca2+, Sr2+, Ba2+, Co2+, Cu2+, Mg2+, and Zn2+ were all effective. Both phenylmethylsulfonylfluoride and diisopropylfluorophosphate were powerful inhibitors of protease activity, but L-1-tosylamide-2-phenylethylchloromethyl ketone, iodoacetic acid, and iodoacetamide were without effect. The enzyme hydrolyzed the esters N-acetyl-L-tyrosine ethyl ester and alpha-N-benzoyl-L-arginine ethyl ester (BAEE) with Km values of 10.4 and 3.4 mM, respectively. The hydrolysis of BAEE was also inhibited by phenylarsonic acids. The kinetics of inhibition by m-nitrophenylarsonate were of the mixed type, and the K1 was 1.8 mM. The data followed a theoretical curve for a 1:1 enzyme-inhibitor complex with a dissociation constant of 1.8 mM. Inhibition by m-nitrophenylarsonate was pH dependent and followed a theoretical curve for the titration of a protonated group with a pKa of 7.0."}
{"id": "PMID:234951", "title": "Induction of hepatic tyrosine aminotransferase in vivo by derivatives of cyclic adenosine 3':5'-monophosphate.", "content": "A number of 8- and N6-SUBSTITUTED DERIVATIVES OF CYCLIC ADENOSINE 3':5'-MONOPHOSPHATE-DEPENDENT PROTEIN KINASE, AND AS SUBSTRATES FOR RAT LIVER CYCLIC NUCLEOTIDE PHOSPHODIESTERASE. All of the analogs tested were able to induce the transaminase. The induction by the analogs was shown to be the result of an actual increase in the amount of enzyme, and the mechanism of induction was an increase in the rate of synthesis of the transaminase. The induced enzyme appeared to be immunologically similar to the non-induced enzyme. A good correlation was found to exist between the dose that produced 50% of maximal induction and a combination of the activation constant for cyclic adenosine 3':5'-monophosphate-dependent protein kinase by the analog and its susceptibility to hydrolysis by cyclic nucleotide phosphodiesterase. These data suggest that the phosphorylation of some site is involved in the mechanism by which cyclic adenosine 3':5'-monophosphate affects the rate of synthesis of tyrosine aminotransferase.", "contents": "Induction of hepatic tyrosine aminotransferase in vivo by derivatives of cyclic adenosine 3':5'-monophosphate. A number of 8- and N6-SUBSTITUTED DERIVATIVES OF CYCLIC ADENOSINE 3':5'-MONOPHOSPHATE-DEPENDENT PROTEIN KINASE, AND AS SUBSTRATES FOR RAT LIVER CYCLIC NUCLEOTIDE PHOSPHODIESTERASE. All of the analogs tested were able to induce the transaminase. The induction by the analogs was shown to be the result of an actual increase in the amount of enzyme, and the mechanism of induction was an increase in the rate of synthesis of the transaminase. The induced enzyme appeared to be immunologically similar to the non-induced enzyme. A good correlation was found to exist between the dose that produced 50% of maximal induction and a combination of the activation constant for cyclic adenosine 3':5'-monophosphate-dependent protein kinase by the analog and its susceptibility to hydrolysis by cyclic nucleotide phosphodiesterase. These data suggest that the phosphorylation of some site is involved in the mechanism by which cyclic adenosine 3':5'-monophosphate affects the rate of synthesis of tyrosine aminotransferase."}
{"id": "PMID:234952", "title": "The essential role of Ca2+ in the activity of bovine pancreatic deoxyribonuclease.", "content": "DNase requires Ca2+ for activity against DNA with Mg2+. The Ca2+ selective chelating agent, ethylene glycol bis(beta-aminoethyl ether)-N, N'-tetraacetic acid, (EGTA) inhibits DNase completely at pH 7 or 8, and subsequent addition of excess Ca2+ reverses inhibition in less than one second. DNase action can be stopped at any point by the addition of excess EGTA over Ca2+. Ca2+ is required for DNase to bind substrate. Gel filtration experiments fail to show DNase binding to 0.2 mg per ml of DNA at 5 mm Mg2+ and 10-4 M EGTA. The concentration of Ca2+ needed for half of maximum DNase activity decreases with increases DNA concentration, from 1.2 times 10-5 M Ca2+ at 2.3 times 10-5 M DNA-P to about 4 times 10-7 M Ca2+ at 2.3 DNA-P. Kinetic analysis by the titrametic assay of protons releases shows that V max is independent of Ca2+ concentration while Km increases from 7.7 times 10-5 M DNA-P at 5 times 10-4 M Ca2+ to 3.4 times 10-4 M DNA-P at 5 times 10-6 M Ca2+. Both of these results are predicted by a rate equation which is derived from the assumption that DNase must bind Ca2+ before it can bind DNA. The essential Ca2+ atom probably binds to the one of two high affinity Ca2+ binding sites on DNase which cannont bind Mg2+ or Mn2+. The only other divalent metal ions which can bind to this site, Sr2+ and Ba2+, are also the only metal ions which can substitute for Ca2+ in DNase action against DNA with Mg2+. Some DNase activity is obtained in the absence of added Ca2+ with Mg2+ at pH 6 or below and with Mn2+ or Co2+ at pH 8. These assay solutions are contaminated by 1 to 3 muM Ca2+, which may be sufficient to account for the observed activity.", "contents": "The essential role of Ca2+ in the activity of bovine pancreatic deoxyribonuclease. DNase requires Ca2+ for activity against DNA with Mg2+. The Ca2+ selective chelating agent, ethylene glycol bis(beta-aminoethyl ether)-N, N'-tetraacetic acid, (EGTA) inhibits DNase completely at pH 7 or 8, and subsequent addition of excess Ca2+ reverses inhibition in less than one second. DNase action can be stopped at any point by the addition of excess EGTA over Ca2+. Ca2+ is required for DNase to bind substrate. Gel filtration experiments fail to show DNase binding to 0.2 mg per ml of DNA at 5 mm Mg2+ and 10-4 M EGTA. The concentration of Ca2+ needed for half of maximum DNase activity decreases with increases DNA concentration, from 1.2 times 10-5 M Ca2+ at 2.3 times 10-5 M DNA-P to about 4 times 10-7 M Ca2+ at 2.3 DNA-P. Kinetic analysis by the titrametic assay of protons releases shows that V max is independent of Ca2+ concentration while Km increases from 7.7 times 10-5 M DNA-P at 5 times 10-4 M Ca2+ to 3.4 times 10-4 M DNA-P at 5 times 10-6 M Ca2+. Both of these results are predicted by a rate equation which is derived from the assumption that DNase must bind Ca2+ before it can bind DNA. The essential Ca2+ atom probably binds to the one of two high affinity Ca2+ binding sites on DNase which cannont bind Mg2+ or Mn2+. The only other divalent metal ions which can bind to this site, Sr2+ and Ba2+, are also the only metal ions which can substitute for Ca2+ in DNase action against DNA with Mg2+. Some DNase activity is obtained in the absence of added Ca2+ with Mg2+ at pH 6 or below and with Mn2+ or Co2+ at pH 8. These assay solutions are contaminated by 1 to 3 muM Ca2+, which may be sufficient to account for the observed activity."}
{"id": "PMID:234953", "title": "The role of metal in liver alcohol dehydrogenase catalysis. Spectral and kinetic studies with cobalt-substituted enzyme.", "content": "The kinetic and spectral properties of native and totally cobalt-substituted liver alcohol dehydrogenase have been compared. Based on titrimetric determinations of enzyme active site concentration, the turnover number at pH 7.0 for cobalt enzyme was the same as for native enzyme. At pH 10, however, the turnover number was slower for cobalt-substituted enzyme, 3.14 s-1 as compared with 4.05 s-1 for native enzyme. A comparison between native and totally cobalt-substituted enzyme showed a blue-shifted enzyme-NADH double difference spectrum and a splitting and red-shifted enzyme-NAD+-pyrazole double difference spectrum in the near-ultraviolet. The 655-nm peak of the cobalt-substituted enzyme was perturbed by the formation of enzyme-NADH binary complex, enzyme-NAD+-trifloroethanol ternary complex, and enzyme-NAD+ binary complex formation. At pH 7.0, the only observable step in the reaction sequence with a significantly different rate constant for cobalt enzyme was the catalytic hydrogen-transferring step. The rate constant for this step is 92 s-1 for totally cobalt-substituted enzyme as compared with 138 s-1 for native liver alcohol dehydrogenase. The results of this study indicate that zinc is involved in catalysis alcohol and NADH.", "contents": "The role of metal in liver alcohol dehydrogenase catalysis. Spectral and kinetic studies with cobalt-substituted enzyme. The kinetic and spectral properties of native and totally cobalt-substituted liver alcohol dehydrogenase have been compared. Based on titrimetric determinations of enzyme active site concentration, the turnover number at pH 7.0 for cobalt enzyme was the same as for native enzyme. At pH 10, however, the turnover number was slower for cobalt-substituted enzyme, 3.14 s-1 as compared with 4.05 s-1 for native enzyme. A comparison between native and totally cobalt-substituted enzyme showed a blue-shifted enzyme-NADH double difference spectrum and a splitting and red-shifted enzyme-NAD+-pyrazole double difference spectrum in the near-ultraviolet. The 655-nm peak of the cobalt-substituted enzyme was perturbed by the formation of enzyme-NADH binary complex, enzyme-NAD+-trifloroethanol ternary complex, and enzyme-NAD+ binary complex formation. At pH 7.0, the only observable step in the reaction sequence with a significantly different rate constant for cobalt enzyme was the catalytic hydrogen-transferring step. The rate constant for this step is 92 s-1 for totally cobalt-substituted enzyme as compared with 138 s-1 for native liver alcohol dehydrogenase. The results of this study indicate that zinc is involved in catalysis alcohol and NADH."}
{"id": "PMID:234954", "title": "Effects of temperature on diphosphopyridine nucleotide-linked isocitrate dehydrogenase from bovine heart. Aspects of the kinetics, stability, and quarternary structure of the enzyme.", "content": "A temperature-dependent conformational change of the active DPN-linked isocitrate dehydrogenase was observed. When initial reaction kinetic data were examined between 35 and 5 degrees, the Hill number (n) varied from 2 at higher to n approaching unity at lower temperatures, with an inflection point at 17 degrees. The presence of manganous isocitrate in the incubation media shifted the transition temperature for enzyme inactivation by 5,5'-dithiobis(2-nitrobenzoate) from 8-16 degrees. These temperature-dependent transitions were paralleled by progressive changes in sedimentation velocities from s20, w of 10.4 at 25 degrees to 7.3 at 10 degrees as measured by active band centrifugation. The linear Arrhenius plot for apparent V max and the constancy of S0.5 for the substrate manganous isocitrate between 35 and 5 degrees suggest that this temperature-dependent conformational change may not be solely related to manganous isocitrate. Further indications of equilibria between different species of enzyme in solution and effects of substrates and cofactors on conformation came from studies of specific activity of enzyme diluted into buffers at 3 and 25 degrees. Dilution to concentrations between 10 and 25 mum enzyme resulted in relatively rapid protein concentration-dependent inactivation which could be prevented and fully reversed by manganous isocitrate. No further substantial inactivation was found subsequent to this phase at 25 degrees. Lowering the temperature of the dilution buffer to 3 degrees favored formation of enzyme species exhibiting a further time and pH-dependent loss of activity which became independent of protein concentration below 7 mum enzyme. The rate of cold inactivation was reduced by raising the ionic strength of the buffer and its progress could be arrested by manganous isocitrate; however, the substrate did not restore the original activity.", "contents": "Effects of temperature on diphosphopyridine nucleotide-linked isocitrate dehydrogenase from bovine heart. Aspects of the kinetics, stability, and quarternary structure of the enzyme. A temperature-dependent conformational change of the active DPN-linked isocitrate dehydrogenase was observed. When initial reaction kinetic data were examined between 35 and 5 degrees, the Hill number (n) varied from 2 at higher to n approaching unity at lower temperatures, with an inflection point at 17 degrees. The presence of manganous isocitrate in the incubation media shifted the transition temperature for enzyme inactivation by 5,5'-dithiobis(2-nitrobenzoate) from 8-16 degrees. These temperature-dependent transitions were paralleled by progressive changes in sedimentation velocities from s20, w of 10.4 at 25 degrees to 7.3 at 10 degrees as measured by active band centrifugation. The linear Arrhenius plot for apparent V max and the constancy of S0.5 for the substrate manganous isocitrate between 35 and 5 degrees suggest that this temperature-dependent conformational change may not be solely related to manganous isocitrate. Further indications of equilibria between different species of enzyme in solution and effects of substrates and cofactors on conformation came from studies of specific activity of enzyme diluted into buffers at 3 and 25 degrees. Dilution to concentrations between 10 and 25 mum enzyme resulted in relatively rapid protein concentration-dependent inactivation which could be prevented and fully reversed by manganous isocitrate. No further substantial inactivation was found subsequent to this phase at 25 degrees. Lowering the temperature of the dilution buffer to 3 degrees favored formation of enzyme species exhibiting a further time and pH-dependent loss of activity which became independent of protein concentration below 7 mum enzyme. The rate of cold inactivation was reduced by raising the ionic strength of the buffer and its progress could be arrested by manganous isocitrate; however, the substrate did not restore the original activity."}
{"id": "PMID:234955", "title": "Complexation of iron hexacyanides by cytochrome c. Evidence for electron exchange at the exposed heme edge.", "content": "Electrostatic binding of at least two anionic iron hexacyanides to cationic horse heart cytochrome c was demonstrated by equilibrium dialysis measurements. No binding was detected following trifluoroacetylation of all of the 19 lysine residues. Replacement of the natural heme iron ligand methionine 80 by the alternative intrinsic ligand lysine 79 but not the extrinsic ligand imidazole resulted in the loss of one hexacyanide binding site. It is proposed that this site is located at the exposed heme edge and is functional in electron exchange.", "contents": "Complexation of iron hexacyanides by cytochrome c. Evidence for electron exchange at the exposed heme edge. Electrostatic binding of at least two anionic iron hexacyanides to cationic horse heart cytochrome c was demonstrated by equilibrium dialysis measurements. No binding was detected following trifluoroacetylation of all of the 19 lysine residues. Replacement of the natural heme iron ligand methionine 80 by the alternative intrinsic ligand lysine 79 but not the extrinsic ligand imidazole resulted in the loss of one hexacyanide binding site. It is proposed that this site is located at the exposed heme edge and is functional in electron exchange."}
{"id": "PMID:234956", "title": "Phosphate-independent glutaminase from rat kidney. Partial purification and identity with gamma-glutamyltranspeptidase.", "content": "Phosphate-independent glutaminase can be quantitatively solubilized from a microsomal preparation of rat kidney by treatment with papain. Subsequent gel filtration and chromatography on quaternary aminoethyl (QAE)-Sephadex and hydroxylapatite yield a 200-fold purified preparation of this glutaminase. The purified enzyme also hydrolyzes gamma-glutamylhydroxamate and exhibits substrate inhibition at high concentrations of either glutamine or gamma-glutamyhydroxamate, which is partially relieved by increasing concentrations of maleate. Rat kidney phosphate-independent glutaminase reaction is catalyzed by the same enzyme which catalyzes the gamma-glutamyltranspeptidase reaction. The ratio of glutaminase to transpeptidase activities remained constant throughout a 200-fold purification of this enzyme. The observation that the phosphate0independent glutaminase and gamma-glutamyltranspeptidase activities exhibit coincident mobilities during electrophoresis, both before and after extensive treatment with neuraminidase, strongly suggests that both reactions are catalyzed by the same enzyme. This conclusion is strengthened by the observation that maleate and various amino acids have reciprocal effects on the two activities. Maleate increases glutaminase activity and blocks transpeptidation, whereas amino acids activate the transpeptidase but inhibit glutaminase activity. In contrast, the addition of both maleate and alanine resulted in a strong inhibition of both activities. Both activities exhibit a similar distribution in the various regions of the kidney. Recovery of maximal activities in the outer stripe region of the medulla is consistent with previous quantitative microanalysis which indicated that this glutaminase activity is localized primarily in the proximal straight tubule cells. The glutaminase and transpeptidase activities have different pH optima. Examination of the product specificity suggests that decreasing pH also promotes glutaminase activity and that below pH 6.0, this enzyme functions strictly as a glutaminase. Because of the localization of this activity on the brush border membrane, these resuts are consistent with the possibility that the physiological conditions induced by metabolic acidosis could convert this enzyme from a broad specificity transpeptidase to a glutaminase. Therefore, this enzyme could contribute to the increased renal synthesis of ammonia from glutamine which is observed during metabolic acidosis.", "contents": "Phosphate-independent glutaminase from rat kidney. Partial purification and identity with gamma-glutamyltranspeptidase. Phosphate-independent glutaminase can be quantitatively solubilized from a microsomal preparation of rat kidney by treatment with papain. Subsequent gel filtration and chromatography on quaternary aminoethyl (QAE)-Sephadex and hydroxylapatite yield a 200-fold purified preparation of this glutaminase. The purified enzyme also hydrolyzes gamma-glutamylhydroxamate and exhibits substrate inhibition at high concentrations of either glutamine or gamma-glutamyhydroxamate, which is partially relieved by increasing concentrations of maleate. Rat kidney phosphate-independent glutaminase reaction is catalyzed by the same enzyme which catalyzes the gamma-glutamyltranspeptidase reaction. The ratio of glutaminase to transpeptidase activities remained constant throughout a 200-fold purification of this enzyme. The observation that the phosphate0independent glutaminase and gamma-glutamyltranspeptidase activities exhibit coincident mobilities during electrophoresis, both before and after extensive treatment with neuraminidase, strongly suggests that both reactions are catalyzed by the same enzyme. This conclusion is strengthened by the observation that maleate and various amino acids have reciprocal effects on the two activities. Maleate increases glutaminase activity and blocks transpeptidation, whereas amino acids activate the transpeptidase but inhibit glutaminase activity. In contrast, the addition of both maleate and alanine resulted in a strong inhibition of both activities. Both activities exhibit a similar distribution in the various regions of the kidney. Recovery of maximal activities in the outer stripe region of the medulla is consistent with previous quantitative microanalysis which indicated that this glutaminase activity is localized primarily in the proximal straight tubule cells. The glutaminase and transpeptidase activities have different pH optima. Examination of the product specificity suggests that decreasing pH also promotes glutaminase activity and that below pH 6.0, this enzyme functions strictly as a glutaminase. Because of the localization of this activity on the brush border membrane, these resuts are consistent with the possibility that the physiological conditions induced by metabolic acidosis could convert this enzyme from a broad specificity transpeptidase to a glutaminase. Therefore, this enzyme could contribute to the increased renal synthesis of ammonia from glutamine which is observed during metabolic acidosis."}
{"id": "PMID:234957", "title": "Kinetic studies on pig heart cytoplasmic malate dehydrogenase.", "content": "Kinetic studies on the pig heart cytoplasmic malate dehydrogenase have been performed over a wide range of conditions using the full time course of the reaction and computer simulation to obtain the kinetic parameters. The maximum velocity and Michaelis constants for the oxidation of reduced coenzyme have been determined as a fundtion of pH in 0.05 M phosphate buffer at 15 degrees. At pH 7.5 and at low substrate concentrations, the kinetic data are consistent with a sequential addition of substrates, coenzyme binding first, and involving the formation of at least one ternary complex. No oxalacetate binding to the enzyme was observed. The rate constants for the dissociation of coenzyme from the enzyme-coenzyme complex are small enough to define the maximum velocity in either direction of the reaction. These data, plus data using deuterated reduced coenzyme, indicate that the chemical transformation step is not rate determining. It is also shown that DPNH binding can be tight enough to practically exclude the possibility of obtaining initial velocities when measuring the reduction of DPN. Kinetic abnormalities do appear at higher substrate or product concentrations, but these do not appear to be related to the formation of inactive abortice, complexes.", "contents": "Kinetic studies on pig heart cytoplasmic malate dehydrogenase. Kinetic studies on the pig heart cytoplasmic malate dehydrogenase have been performed over a wide range of conditions using the full time course of the reaction and computer simulation to obtain the kinetic parameters. The maximum velocity and Michaelis constants for the oxidation of reduced coenzyme have been determined as a fundtion of pH in 0.05 M phosphate buffer at 15 degrees. At pH 7.5 and at low substrate concentrations, the kinetic data are consistent with a sequential addition of substrates, coenzyme binding first, and involving the formation of at least one ternary complex. No oxalacetate binding to the enzyme was observed. The rate constants for the dissociation of coenzyme from the enzyme-coenzyme complex are small enough to define the maximum velocity in either direction of the reaction. These data, plus data using deuterated reduced coenzyme, indicate that the chemical transformation step is not rate determining. It is also shown that DPNH binding can be tight enough to practically exclude the possibility of obtaining initial velocities when measuring the reduction of DPN. Kinetic abnormalities do appear at higher substrate or product concentrations, but these do not appear to be related to the formation of inactive abortice, complexes."}
{"id": "PMID:234959", "title": "The nonspecific binding of Fe3+ to transferrin in the absence of synergistic anions.", "content": "An obligatory role for barbonate (or other synergistic anions) in the specific binding of Fe3+ by transferrin has been a point of controversy for two decades. There are an equal number of confirmatory and negative reports of specific Fe3+-transferrin binary complexes. A criticism of previous studies is the use of only one synthetic route, and limited product testing. This study reports the development of several preparative routes aimed at the formation of a specific Fe3+-transferrin complex, and the characterization of the products by spectrophotometry and chemical reactivity. The preparative routes described include: (a) displacement of carbonate from Fe3+-transferrin-CO32- at low pH followed by removal of CO2 by several techniques; (b) addition of FeCl3 to apotransferrin under CO2-free conditions; (c) oxidation of Fe2+ in the presence of apotransferrin under CO2-free conditions; (d) reaction of apotransferrin with nonsubstituting Fe3+ complexes in the absence of CO2; and (e) attempts to displace anions from weak Fe3+-transferrin-anion complexes. The product were examined with regard to their visible spectra, and their examined with regard to their visible spectra, and their reactivity with: (a) NaHCO3, (b) Fe3+-nitrilotriacetic acid in NaHCO3, and (c) citrate. The results are compared with the characteristics of Fe3+-transferrin-anion complexes and nonspecific Fe3+, transferrin mixtures. The data indicate that in the absence of synergistic anions the affinity of the specific metal binding sites of transfe-rin for Fe3+ is so low as to not compete favorably with hydrolytic polymerization and nonspecific binding effects.", "contents": "The nonspecific binding of Fe3+ to transferrin in the absence of synergistic anions. An obligatory role for barbonate (or other synergistic anions) in the specific binding of Fe3+ by transferrin has been a point of controversy for two decades. There are an equal number of confirmatory and negative reports of specific Fe3+-transferrin binary complexes. A criticism of previous studies is the use of only one synthetic route, and limited product testing. This study reports the development of several preparative routes aimed at the formation of a specific Fe3+-transferrin complex, and the characterization of the products by spectrophotometry and chemical reactivity. The preparative routes described include: (a) displacement of carbonate from Fe3+-transferrin-CO32- at low pH followed by removal of CO2 by several techniques; (b) addition of FeCl3 to apotransferrin under CO2-free conditions; (c) oxidation of Fe2+ in the presence of apotransferrin under CO2-free conditions; (d) reaction of apotransferrin with nonsubstituting Fe3+ complexes in the absence of CO2; and (e) attempts to displace anions from weak Fe3+-transferrin-anion complexes. The product were examined with regard to their visible spectra, and their examined with regard to their visible spectra, and their reactivity with: (a) NaHCO3, (b) Fe3+-nitrilotriacetic acid in NaHCO3, and (c) citrate. The results are compared with the characteristics of Fe3+-transferrin-anion complexes and nonspecific Fe3+, transferrin mixtures. The data indicate that in the absence of synergistic anions the affinity of the specific metal binding sites of transfe-rin for Fe3+ is so low as to not compete favorably with hydrolytic polymerization and nonspecific binding effects."}
{"id": "PMID:234960", "title": "Identification of a folate binder in hog kidney.", "content": "A macromolecular binder of folic acid (pteroylglutamic acid) and folic acid derivatives has been identified in extracts of hog kidney. With partially purified preparations, binding of [3H]pteroylglutamate was competed for by unlabeled pteroylglutamate, 5-methyltetrahydrofolic acid and its triglutamate derivative, by tetra- and dihydrofolic acid, and by N-10-formyltetrahydrofolic acid. The partially purified extract did not bine [3H]methotrexate nor could methotrexate or 5-formyltetrahydrofolic acid compete for [3H]folic acid-binding sites. The rate of binding of pterolyglutamate at 37 degrees was approximately 3%/s, was independent of pteroylglutamate concentration, and was essentially irreversible between pH 6.0 and 9.0. Below pH 6.0 binding was reversible, and at pH 3.5 the folic acid-binder complex completely disassociated. Based upon Sephadex gel filtration, the molecular weight of the folate-binder complex is 35,000 to 40,000. Binding activity was unaffected by pretreatment with ribonuclease or deoxyribonuclease but was completely destroyed by trypsin. The initial, unfractionated extract showed gamma-glutamyl carboxypeptidase (conjugase) activity which was lost in subsequent steps of purification of the folate binder.", "contents": "Identification of a folate binder in hog kidney. A macromolecular binder of folic acid (pteroylglutamic acid) and folic acid derivatives has been identified in extracts of hog kidney. With partially purified preparations, binding of [3H]pteroylglutamate was competed for by unlabeled pteroylglutamate, 5-methyltetrahydrofolic acid and its triglutamate derivative, by tetra- and dihydrofolic acid, and by N-10-formyltetrahydrofolic acid. The partially purified extract did not bine [3H]methotrexate nor could methotrexate or 5-formyltetrahydrofolic acid compete for [3H]folic acid-binding sites. The rate of binding of pterolyglutamate at 37 degrees was approximately 3%/s, was independent of pteroylglutamate concentration, and was essentially irreversible between pH 6.0 and 9.0. Below pH 6.0 binding was reversible, and at pH 3.5 the folic acid-binder complex completely disassociated. Based upon Sephadex gel filtration, the molecular weight of the folate-binder complex is 35,000 to 40,000. Binding activity was unaffected by pretreatment with ribonuclease or deoxyribonuclease but was completely destroyed by trypsin. The initial, unfractionated extract showed gamma-glutamyl carboxypeptidase (conjugase) activity which was lost in subsequent steps of purification of the folate binder."}
{"id": "PMID:234961", "title": "The effects of polyamines on a residue-specific human plasma ribonuclease.", "content": "A ribonuclease, purified some 2700-fold from human plasma, exhibited a strong predilection for the hydrolysis of internucleotide bonds containing cytidylic acid. Analysis of [3'-32P]- and [5'-32P]phosphoryl-terminal fragments obtained after enzymic digestion of rabbit liver and yeast RNA indicated that the nucleotide found at the 3' terminus of the fragments was invariably cytidylic acid. The nucleotide at the 5' terminus varied between cytidylic and uridylic acids in a ratio of 9:1. When characterized by DEAE-cellulose chromatography, approximately 70 per cent of the digest consisted of oligonucleotides from 4 to 8 nucleotides in length. Enzyme activity, when measured in low ionic strength buffer, could be increased severalfold above control levels by the addition of either of the polyamines, spermidine or spermine. These substances also restored nucleolytic activity to preparations inhibited by such ordered synthetic polyribonucleotides as polyguanylic acid. Estimations of the molecular weight of the enzyme, both by Sephadex gel filtration and sucrose density centrifugation, indicate that the weight may vary, depending on the presence or absence of certain cations. Of the cations examined, spermidine and spermine appear to have the greatest effect, causing an alteration in molecular weight from greater than 150,000 to approximately 32,000.", "contents": "The effects of polyamines on a residue-specific human plasma ribonuclease. A ribonuclease, purified some 2700-fold from human plasma, exhibited a strong predilection for the hydrolysis of internucleotide bonds containing cytidylic acid. Analysis of [3'-32P]- and [5'-32P]phosphoryl-terminal fragments obtained after enzymic digestion of rabbit liver and yeast RNA indicated that the nucleotide found at the 3' terminus of the fragments was invariably cytidylic acid. The nucleotide at the 5' terminus varied between cytidylic and uridylic acids in a ratio of 9:1. When characterized by DEAE-cellulose chromatography, approximately 70 per cent of the digest consisted of oligonucleotides from 4 to 8 nucleotides in length. Enzyme activity, when measured in low ionic strength buffer, could be increased severalfold above control levels by the addition of either of the polyamines, spermidine or spermine. These substances also restored nucleolytic activity to preparations inhibited by such ordered synthetic polyribonucleotides as polyguanylic acid. Estimations of the molecular weight of the enzyme, both by Sephadex gel filtration and sucrose density centrifugation, indicate that the weight may vary, depending on the presence or absence of certain cations. Of the cations examined, spermidine and spermine appear to have the greatest effect, causing an alteration in molecular weight from greater than 150,000 to approximately 32,000."}
{"id": "PMID:234962", "title": "PH dependence of the Adair constants of human hemoglobin. Nonuniform contribution of successive oxygen bindings to the alkaline Bohr effect.", "content": "In order to solve the problem of an apparent discrepancy between the pH variance of oxygen equilibrium curve and the linear relation between the number of released Bohr protons and the degree of ligation, precise oxygen equilibrium curves of human hemoglobin were determined at a number of pH values from 6.5 to 8.8. From the equilibrium data individual steps (Adair constants), ki (i equals 1, 2, 3, 4), were obtained and the number of Bohr protons (deltaHi+) released on the ith stage of oxygenation was estimated. The pH dependence of k4 was very small, while the other ks strongly depended on pH over the pH range examined. As a consequence, the contribution of each step of oxygen binding to the alkaline Bohr effect nonuniform: deltaH4 was very small compared with deltaH1+, deltaH2+, and deltaH3+. In spite of this, calcuation has shown that the fractional number of released protons is essentially proportional to fractional oxygen saturation because of cooperative effects in hemoglobin. Thus, the present study indicates that the linear relationship between the fractional number of released protons and the degree of ligation, as obtained from titration experiments, is not necessarily incompatible with the pH variance of the shape of the oxygen equilibrium curve. The nonuniform pH depencence of the Adair constants implies that the two-state allosteric model of Monod, J., Wyman, J., and Changeus, J.P. (1965) J. Mol. Biol. 12, 88-118 is not adequate to describe the heterotropic effect caused by protons.", "contents": "PH dependence of the Adair constants of human hemoglobin. Nonuniform contribution of successive oxygen bindings to the alkaline Bohr effect. In order to solve the problem of an apparent discrepancy between the pH variance of oxygen equilibrium curve and the linear relation between the number of released Bohr protons and the degree of ligation, precise oxygen equilibrium curves of human hemoglobin were determined at a number of pH values from 6.5 to 8.8. From the equilibrium data individual steps (Adair constants), ki (i equals 1, 2, 3, 4), were obtained and the number of Bohr protons (deltaHi+) released on the ith stage of oxygenation was estimated. The pH dependence of k4 was very small, while the other ks strongly depended on pH over the pH range examined. As a consequence, the contribution of each step of oxygen binding to the alkaline Bohr effect nonuniform: deltaH4 was very small compared with deltaH1+, deltaH2+, and deltaH3+. In spite of this, calcuation has shown that the fractional number of released protons is essentially proportional to fractional oxygen saturation because of cooperative effects in hemoglobin. Thus, the present study indicates that the linear relationship between the fractional number of released protons and the degree of ligation, as obtained from titration experiments, is not necessarily incompatible with the pH variance of the shape of the oxygen equilibrium curve. The nonuniform pH depencence of the Adair constants implies that the two-state allosteric model of Monod, J., Wyman, J., and Changeus, J.P. (1965) J. Mol. Biol. 12, 88-118 is not adequate to describe the heterotropic effect caused by protons."}
{"id": "PMID:234963", "title": "Transport and metabolism of folates by bacteria.", "content": "Transport of labeled folic acid (PteGlu), pteroylpolyglutamates (PteGlu3-5), 5-methyl-tetrahydrofolate (5-methyl-H4PteGlu), and methotrexate in late-log phase cells of Lactobacillus casei was active, and subject to inhibition by unlabeled pteroylmonoglutamates, pteroylpolyglutamates, and iodoacetate, but not glutamate or glutamate dipeptides. Pteroylpolyglutamates were transported without prior hydrolysis and shared a common uptake system with pteroylmonoglutamates. The affinity and maximum velocity of PteGlun uptake decreased with increasing glutamate chin length (Km:PteGlu1, 0.03 mum; PteGlu3, 0.32 mum; PteGlu4, 1.9 mum; PteGlu5, 3.7 mum) and comparisons with growth response curves suggested that polyglutamates were more effectively utilized by L. casei, once transported, than monoglutamate. No concentration of 5-methyl-H4PteGlu3-8 inside the cells was observed. The major folate metabolites found in L. casei preloaded with high levels of [3H]PteGlu (0.5 mum) were 10-formyl-H4PteGlu2 and 10-formyl-PteGlu. Both compounds were released, the monoglutamate more rapidly. Pteroyltriglutamate formation appeared to be a rate-limiting step in intracellular metabolism. No 10-formyl-Pte-Glu was found in iodoacetate-treated cells and efflux was inhibited. Cells preloaded with low levels of [3H]PteGlu (7 nm) metabolized the vitamin to polyglutamate forms, the major derivatives being H4PteGlun. First order exit rates of labeled folate from preloaded L. casei indicated an inhibition of PteGlu uptake with time. Exit rates dropped from 0.05 min-1 to greater than 0.002 min-1 as intracellular folate was metabolized from monoglutamate to polyglutamate derivatives (n larger than or equal to 3). In the latter case, materials lost by efflux were breakdown products and no folate of glutamate chain length greater than two was released. Pediococcus cerevisiae actively transported 5-methyl-H4PteGlu but did not take up to 5-methyl-H4PTeGlu3-8. No active accumulation of 5-methyl-H4PteGlu was observed in Streptococcus faecalis.", "contents": "Transport and metabolism of folates by bacteria. Transport of labeled folic acid (PteGlu), pteroylpolyglutamates (PteGlu3-5), 5-methyl-tetrahydrofolate (5-methyl-H4PteGlu), and methotrexate in late-log phase cells of Lactobacillus casei was active, and subject to inhibition by unlabeled pteroylmonoglutamates, pteroylpolyglutamates, and iodoacetate, but not glutamate or glutamate dipeptides. Pteroylpolyglutamates were transported without prior hydrolysis and shared a common uptake system with pteroylmonoglutamates. The affinity and maximum velocity of PteGlun uptake decreased with increasing glutamate chin length (Km:PteGlu1, 0.03 mum; PteGlu3, 0.32 mum; PteGlu4, 1.9 mum; PteGlu5, 3.7 mum) and comparisons with growth response curves suggested that polyglutamates were more effectively utilized by L. casei, once transported, than monoglutamate. No concentration of 5-methyl-H4PteGlu3-8 inside the cells was observed. The major folate metabolites found in L. casei preloaded with high levels of [3H]PteGlu (0.5 mum) were 10-formyl-H4PteGlu2 and 10-formyl-PteGlu. Both compounds were released, the monoglutamate more rapidly. Pteroyltriglutamate formation appeared to be a rate-limiting step in intracellular metabolism. No 10-formyl-Pte-Glu was found in iodoacetate-treated cells and efflux was inhibited. Cells preloaded with low levels of [3H]PteGlu (7 nm) metabolized the vitamin to polyglutamate forms, the major derivatives being H4PteGlun. First order exit rates of labeled folate from preloaded L. casei indicated an inhibition of PteGlu uptake with time. Exit rates dropped from 0.05 min-1 to greater than 0.002 min-1 as intracellular folate was metabolized from monoglutamate to polyglutamate derivatives (n larger than or equal to 3). In the latter case, materials lost by efflux were breakdown products and no folate of glutamate chain length greater than two was released. Pediococcus cerevisiae actively transported 5-methyl-H4PteGlu but did not take up to 5-methyl-H4PTeGlu3-8. No active accumulation of 5-methyl-H4PteGlu was observed in Streptococcus faecalis."}
{"id": "PMID:234964", "title": "The molecular behavior of apoA-I in human high density lipoproteins.", "content": "The properties of apoA-I in human high density lipoprotein (1.063 smaller than d smaller than 1.210 gm per ml) have been examined by fluorescence and difference absorption spectroscopy, while the behavior of the total complement of apoproteins has been evaluated by far ultraviolet circular dichroism. Marked increases in stability to temperature, pH, and guanidine hydrochloride were observed for apoA-I in the native particle as compared to the isolated state.", "contents": "The molecular behavior of apoA-I in human high density lipoproteins. The properties of apoA-I in human high density lipoprotein (1.063 smaller than d smaller than 1.210 gm per ml) have been examined by fluorescence and difference absorption spectroscopy, while the behavior of the total complement of apoproteins has been evaluated by far ultraviolet circular dichroism. Marked increases in stability to temperature, pH, and guanidine hydrochloride were observed for apoA-I in the native particle as compared to the isolated state."}
{"id": "PMID:234965", "title": "On the structure-function relationship of acyl carrier protein of Escherichia coli.", "content": "The conformations of Escherichia coli acyl carrier protein (ACP) and acetylated ACP have been studied as a function of pH and salt concentration by circular dichroism measurements. The results show that the amino groups of ACP in their protonated form  are important for maintaining the native conformation of the protein at physiological pH. However, externally added cations (divalent more effectively than monovalent ones) can substitute for the ammonium groups in maintaining the ordered structure pf ACP. It is suggested that both the ammonium groups of ACP and externally added cations reduce the repulsion between carboxylate groups of ACP and thereby prevent the unfolding of the protein. A reduction of the number of negatively charged carboxylate groups by either protonation or chemical modification abolished the requirement for either ammonium groups or other cations. A qualitative agreement between the effect of salt on the conformation and on the biological activity of acetylated ACP has been observed. The single arginine residue of acetylated ACP has been modified by treatment with a trimer of 2,3-butanedione with the resulting derivative of ACP retaining most of its biological activity.", "contents": "On the structure-function relationship of acyl carrier protein of Escherichia coli. The conformations of Escherichia coli acyl carrier protein (ACP) and acetylated ACP have been studied as a function of pH and salt concentration by circular dichroism measurements. The results show that the amino groups of ACP in their protonated form  are important for maintaining the native conformation of the protein at physiological pH. However, externally added cations (divalent more effectively than monovalent ones) can substitute for the ammonium groups in maintaining the ordered structure pf ACP. It is suggested that both the ammonium groups of ACP and externally added cations reduce the repulsion between carboxylate groups of ACP and thereby prevent the unfolding of the protein. A reduction of the number of negatively charged carboxylate groups by either protonation or chemical modification abolished the requirement for either ammonium groups or other cations. A qualitative agreement between the effect of salt on the conformation and on the biological activity of acetylated ACP has been observed. The single arginine residue of acetylated ACP has been modified by treatment with a trimer of 2,3-butanedione with the resulting derivative of ACP retaining most of its biological activity."}
{"id": "PMID:234966", "title": "Ketopantoic acid and ketopantoyl lactone reductases. Stereospecificity of transfer of hydrogen from reduced nicotinamide adenine dinucleotide phosphate.", "content": "The stereospecificity of hydrogen transfer from NADPH to the appropriate carbonyl substrate catalyzed by ketopantoic acid and ketopantoyl acid and ketopantoyl lactone reductases of yeast (Saccharomyces cerevisiae) and Escherichia coli has been determined. Yeast and E. coli ketopantoic acid reductases are B-specific enzymes which transfer hydrogen from [4B-3H]-NADPH to ketopantoic acid to form [3H]pantoic acid. In contrast to the usual observations on the stereospecificity of functionally similar dehydrogenases from different species, yeast and E. coli ketopantoyl lactone reductases exhibit opposite stereospecificities. Both of two forms of yeast ketopantoyl lactone reductases are A-specific enzymes which form [3H]pantoyl lactone from ketopantoyl lactone and [4A-3H]NADPH, whereas, two forms of E. coli ketopantoyl lactone reductases are B-specific enzymes.", "contents": "Ketopantoic acid and ketopantoyl lactone reductases. Stereospecificity of transfer of hydrogen from reduced nicotinamide adenine dinucleotide phosphate. The stereospecificity of hydrogen transfer from NADPH to the appropriate carbonyl substrate catalyzed by ketopantoic acid and ketopantoyl acid and ketopantoyl lactone reductases of yeast (Saccharomyces cerevisiae) and Escherichia coli has been determined. Yeast and E. coli ketopantoic acid reductases are B-specific enzymes which transfer hydrogen from [4B-3H]-NADPH to ketopantoic acid to form [3H]pantoic acid. In contrast to the usual observations on the stereospecificity of functionally similar dehydrogenases from different species, yeast and E. coli ketopantoyl lactone reductases exhibit opposite stereospecificities. Both of two forms of yeast ketopantoyl lactone reductases are A-specific enzymes which form [3H]pantoyl lactone from ketopantoyl lactone and [4A-3H]NADPH, whereas, two forms of E. coli ketopantoyl lactone reductases are B-specific enzymes."}
{"id": "PMID:234967", "title": "Catalytic acitivity of Ntau-carboxymethylhistidine-12 ribonuclease.", "content": "Ntau-Carboxymethylhistidine-12 RNase is active with both RNA and uridine cyclic 2':3'-monophosphate as substrates. Experimental evidence is presented to show that the activity cannot be due to contaminating RNase A, or other RNase-type protein, to the presence of a mixed dimer between 12- and 119-substituted RNases, or to the presence of trace amounts of Ntau-carboxymethylhistidine-12 RNase. The carboxymethyl derivative has approximately 1 and 13 per cent the specific activity of native enzyme against cyclic 2',3'-UMP at pH 5.0 and 8.5, respectively.", "contents": "Catalytic acitivity of Ntau-carboxymethylhistidine-12 ribonuclease. Ntau-Carboxymethylhistidine-12 RNase is active with both RNA and uridine cyclic 2':3'-monophosphate as substrates. Experimental evidence is presented to show that the activity cannot be due to contaminating RNase A, or other RNase-type protein, to the presence of a mixed dimer between 12- and 119-substituted RNases, or to the presence of trace amounts of Ntau-carboxymethylhistidine-12 RNase. The carboxymethyl derivative has approximately 1 and 13 per cent the specific activity of native enzyme against cyclic 2',3'-UMP at pH 5.0 and 8.5, respectively."}
{"id": "PMID:234968", "title": "Long chain fatty acid binding to human plasma albumin.", "content": "The binding of six physiologically important long chain fatty acids to defatted human plasma albumin was measured at 37 degrees in a calcium-free Krebs-Ringer phosphate buffer, pH 7.4. The data were analyzed in terms of multiple stepwise equilibria. With the saturated acids, the magnitude of the equilibrium (association) constants, Ki, increased as the chain length increased: laurate smaller than myristate smaller than palmitate smaller than stearate. Oleate was bound more tightly than stearate; by contrast, linoleate was bound less tightly than stearate. The equilibrium constants, K1 through K12, ranged from 2.4 times 10-6 - 3.5 times 10-3 m-1 for laurate to 2.6 times 10-8 - 3.5 times 10-5 m-1 for oleate. Successive values of Ki decrease for each of the acids, indicating that major cooperative binding effects do not occur over the physiological range of fatty acid concentrations. In no case could the Ki be segregated into distinct classes, suggesting that any grouping of albumin binding sites is somewhat arbitrary. The results were inconclusive concerning whether premicellar association of unbound fatty acid occurs. Although corrections for premicellar association produced very little change in the Ki values for myristate, they raised the Ki for palmitate and stearate by 300 to 700 per cent. A sigmoidal relationship was obtained when the logarithm of Ki was plotted against chain length for the saturated fatty acids containing 6 to 18 carbon atoms, indicating that the binding energy is not simply a statistical process dependent only on the fatty acid chain length. This selectivity that albumin contributes to the binding process may be due to varying degrees of configurational adaptability of its binding sites as the fatty acid increases in length.", "contents": "Long chain fatty acid binding to human plasma albumin. The binding of six physiologically important long chain fatty acids to defatted human plasma albumin was measured at 37 degrees in a calcium-free Krebs-Ringer phosphate buffer, pH 7.4. The data were analyzed in terms of multiple stepwise equilibria. With the saturated acids, the magnitude of the equilibrium (association) constants, Ki, increased as the chain length increased: laurate smaller than myristate smaller than palmitate smaller than stearate. Oleate was bound more tightly than stearate; by contrast, linoleate was bound less tightly than stearate. The equilibrium constants, K1 through K12, ranged from 2.4 times 10-6 - 3.5 times 10-3 m-1 for laurate to 2.6 times 10-8 - 3.5 times 10-5 m-1 for oleate. Successive values of Ki decrease for each of the acids, indicating that major cooperative binding effects do not occur over the physiological range of fatty acid concentrations. In no case could the Ki be segregated into distinct classes, suggesting that any grouping of albumin binding sites is somewhat arbitrary. The results were inconclusive concerning whether premicellar association of unbound fatty acid occurs. Although corrections for premicellar association produced very little change in the Ki values for myristate, they raised the Ki for palmitate and stearate by 300 to 700 per cent. A sigmoidal relationship was obtained when the logarithm of Ki was plotted against chain length for the saturated fatty acids containing 6 to 18 carbon atoms, indicating that the binding energy is not simply a statistical process dependent only on the fatty acid chain length. This selectivity that albumin contributes to the binding process may be due to varying degrees of configurational adaptability of its binding sites as the fatty acid increases in length."}
{"id": "PMID:234969", "title": "Chromatin-associated protein phosphokinases of rat ventral prostate. Characteristics and effects of androgenic status.", "content": "Protein phosphokinase activity endogenous to rat ventral prostate chromatin was assayed by using edphosphophosvitin as an exogenous substrate. For maximal activity of the kinase reaction, the presence of 200 mM NaCl, 5 mM MgCl2, and 1 mM dithiothreitol was essential. Two apparent pH optima were observed, a broad one between pH 7 and 7.4, and one at pH 7.89. At pH 7.4 the apparent Km for 31% dephosphophosvitin was 0.3 mg per ml. With respect to ATP, two apparent Km values (0.04 and 0.41 mM) were found. The kinase activity was minimal toward exogenous histones when used as substrates (3% for lysine-rich and 0.3% for arginine-rich (f3) histones, compared with dephosphophosvitin controls). The protein phosphokinases were not significantly stimulated by cyclic adenosine 3':5'-monophosphate (cyclic AMP) when histones used as substrate. With dephosphophosvitin as substrate, cyclic AMP produced a small inhibition (5 to 15%). Orchiectomy of adult rats resulted in a rapid decline in the chromatin-associated protein phosphokinase activity assayed using optimal experimental condition described above. At 9 hours postorchiectomy, a 30% decline in the activity was observed; this was further reduced to about 50% of the control by 18 hours. This decrease in the kinase activity (e.g. at 9 hours postorchiectomy) appears to precede measurable changes in the protein and RNA complements of chromatin. Testosterone replacement following orchiectomy abolished this decline in the chromatin-associated activity. The chromatin-associated protein phosphokinase activity toward lysine-rich and arginine-rich histones was also sensitive to androgenic status of the animals and declined rapidly postorchiectomy. The results suggest the presence of multiple and androgen-sensitive protien phosphokinases associated with rat ventral prostate chromatin, which may modulate the phosphorylation of nuclear nonhistone phosphoproteins with changing gene action mediated by testosterone in this target tissue.", "contents": "Chromatin-associated protein phosphokinases of rat ventral prostate. Characteristics and effects of androgenic status. Protein phosphokinase activity endogenous to rat ventral prostate chromatin was assayed by using edphosphophosvitin as an exogenous substrate. For maximal activity of the kinase reaction, the presence of 200 mM NaCl, 5 mM MgCl2, and 1 mM dithiothreitol was essential. Two apparent pH optima were observed, a broad one between pH 7 and 7.4, and one at pH 7.89. At pH 7.4 the apparent Km for 31% dephosphophosvitin was 0.3 mg per ml. With respect to ATP, two apparent Km values (0.04 and 0.41 mM) were found. The kinase activity was minimal toward exogenous histones when used as substrates (3% for lysine-rich and 0.3% for arginine-rich (f3) histones, compared with dephosphophosvitin controls). The protein phosphokinases were not significantly stimulated by cyclic adenosine 3':5'-monophosphate (cyclic AMP) when histones used as substrate. With dephosphophosvitin as substrate, cyclic AMP produced a small inhibition (5 to 15%). Orchiectomy of adult rats resulted in a rapid decline in the chromatin-associated protein phosphokinase activity assayed using optimal experimental condition described above. At 9 hours postorchiectomy, a 30% decline in the activity was observed; this was further reduced to about 50% of the control by 18 hours. This decrease in the kinase activity (e.g. at 9 hours postorchiectomy) appears to precede measurable changes in the protein and RNA complements of chromatin. Testosterone replacement following orchiectomy abolished this decline in the chromatin-associated activity. The chromatin-associated protein phosphokinase activity toward lysine-rich and arginine-rich histones was also sensitive to androgenic status of the animals and declined rapidly postorchiectomy. The results suggest the presence of multiple and androgen-sensitive protien phosphokinases associated with rat ventral prostate chromatin, which may modulate the phosphorylation of nuclear nonhistone phosphoproteins with changing gene action mediated by testosterone in this target tissue."}
{"id": "PMID:234970", "title": "Spectroscopic evidence for the generation of singlet oxygen in the reduced nicotinamide adenine dinucleotide phosphate-dependent microsomal lipid peroxidation system.", "content": "In the presence of Fe3+-ADP and NADPH, washed rat liver microsomes at 37 degrees and at pH 7.5 emitted ultraweak light with the peroxidative cleavage of endogenous lipid. The main light-emitting species of this system was analyzed spectroscopically in the visible region and estimated to be singlet oxygen. The addition of superoxide dismutase or catalase did not inhibit the light emission significantly. It is unlikely therefore that superoxide anion and OH are involved in the generation of singlet oxygen in the present system.", "contents": "Spectroscopic evidence for the generation of singlet oxygen in the reduced nicotinamide adenine dinucleotide phosphate-dependent microsomal lipid peroxidation system. In the presence of Fe3+-ADP and NADPH, washed rat liver microsomes at 37 degrees and at pH 7.5 emitted ultraweak light with the peroxidative cleavage of endogenous lipid. The main light-emitting species of this system was analyzed spectroscopically in the visible region and estimated to be singlet oxygen. The addition of superoxide dismutase or catalase did not inhibit the light emission significantly. It is unlikely therefore that superoxide anion and OH are involved in the generation of singlet oxygen in the present system."}
{"id": "PMID:234971", "title": "Injuries of the midtarsal joint.", "content": "Injuries involving the midtarsal joint, which are frequently misdiagnosed, have been studied to clarify the mechanism, classification and treatment. The necessity for routine antero-posterior, lateral and oblique radiographs is emphasised. Seventy-one injuries have been classified according to the direction of the deforming force:medial, longitudinal compression, lateral, plantar and crush types are described. Included in the medial and lateral types is a hitherto undescribed tarsal rotation or \"swivel\" injury. The mechanism whereby longitudinal compression causes fractures of the body of the navicular is described, and two varieties having different prognoses are defined: one due to purely longitudinal compression and the other due to longitudinal compression with a medial component. The results of treatment have been assessed clinically and radiologically. Reduction, open if necessary, with internal fixation, is recommended for displace fractures: primary arthrodesis is not indicated. For severe persistent symptoms from medial and longitudinal force injuries triple arthrodesis is recommended, and from lateral force injuries, calcaneo-cuboid arthrodesis.", "contents": "Injuries of the midtarsal joint. Injuries involving the midtarsal joint, which are frequently misdiagnosed, have been studied to clarify the mechanism, classification and treatment. The necessity for routine antero-posterior, lateral and oblique radiographs is emphasised. Seventy-one injuries have been classified according to the direction of the deforming force:medial, longitudinal compression, lateral, plantar and crush types are described. Included in the medial and lateral types is a hitherto undescribed tarsal rotation or \"swivel\" injury. The mechanism whereby longitudinal compression causes fractures of the body of the navicular is described, and two varieties having different prognoses are defined: one due to purely longitudinal compression and the other due to longitudinal compression with a medial component. The results of treatment have been assessed clinically and radiologically. Reduction, open if necessary, with internal fixation, is recommended for displace fractures: primary arthrodesis is not indicated. For severe persistent symptoms from medial and longitudinal force injuries triple arthrodesis is recommended, and from lateral force injuries, calcaneo-cuboid arthrodesis."}
{"id": "PMID:234972", "title": "Computer analysis of amino acid chromatograms.", "content": "A procedure is described for the automatic off-line analysis of amino acid chromatograms of protein hydrolysates, using a small computer. The data requirements are basic, and, unlike previous programs, the present system allows the separation and identification of bands, as well as the quantitative determination of composition. With minor modification, the program could be extended for use with most types of chromatographic data. The validity of the application of the program to experimental data is discussed.", "contents": "Computer analysis of amino acid chromatograms. A procedure is described for the automatic off-line analysis of amino acid chromatograms of protein hydrolysates, using a small computer. The data requirements are basic, and, unlike previous programs, the present system allows the separation and identification of bands, as well as the quantitative determination of composition. With minor modification, the program could be extended for use with most types of chromatographic data. The validity of the application of the program to experimental data is discussed."}
{"id": "PMID:234973", "title": "Separation of tricyclic psychosedative drugs by high-speed ion-pair partition and liquid-solid adsorption chromatography.", "content": "The application of high-speed ion-pair partition and liquid-solid adsorption chromatography to the separation of twenty common tricyclic tranquilizers and antidepressant drugs is described. In the ion-pair system, amine-perchlorate ion-pairs were extracted from an aqueous stationary phase supported on 10-mum silica gel by organic eluents containing a chloromethane and a higher aliphatic alcohol, and chromatographic parameters for elution by eight eluent mixtures are presented. Using 5 mm times 120 mm columns good separations, according to chemical class, were achieved. For adsorption chromatography, the components were eluted from 20-mum spherical alumina using eluents containing methylene chloride, n-hexane or n-pentane, and acetic acid. Chromatographic parameters are given for eight eluent compositions. Components differing little in structure are well separated by liquid-solid adsorption chromatography. Compared with ion-pair partition chromatography, adsorption chromatography is much more selective for compounds of the same chemical type. The two methods are therefore complementary. Both methods gave plate heights in the range of 0.1 to 0.3 mm.", "contents": "Separation of tricyclic psychosedative drugs by high-speed ion-pair partition and liquid-solid adsorption chromatography. The application of high-speed ion-pair partition and liquid-solid adsorption chromatography to the separation of twenty common tricyclic tranquilizers and antidepressant drugs is described. In the ion-pair system, amine-perchlorate ion-pairs were extracted from an aqueous stationary phase supported on 10-mum silica gel by organic eluents containing a chloromethane and a higher aliphatic alcohol, and chromatographic parameters for elution by eight eluent mixtures are presented. Using 5 mm times 120 mm columns good separations, according to chemical class, were achieved. For adsorption chromatography, the components were eluted from 20-mum spherical alumina using eluents containing methylene chloride, n-hexane or n-pentane, and acetic acid. Chromatographic parameters are given for eight eluent compositions. Components differing little in structure are well separated by liquid-solid adsorption chromatography. Compared with ion-pair partition chromatography, adsorption chromatography is much more selective for compounds of the same chemical type. The two methods are therefore complementary. Both methods gave plate heights in the range of 0.1 to 0.3 mm."}
{"id": "PMID:234974", "title": "Chromatographic separation of conformers of substituted asymmetric nitrosamines.", "content": "The syn and anti conformers of N-nitrosoproline, N-nitrososarcosine and N-nitroso-2-(ethylamino)-ethanol, have been separated by liquid chromatography. These conformers result from hindered rotation about the N-N bond. Separation was achieved using adsorption, reversed-phase, and ion-exchange modes. For the nitroso-amino acids, a shift in the equilibrium conformer concentration was observed with changes in pH.", "contents": "Chromatographic separation of conformers of substituted asymmetric nitrosamines. The syn and anti conformers of N-nitrosoproline, N-nitrososarcosine and N-nitroso-2-(ethylamino)-ethanol, have been separated by liquid chromatography. These conformers result from hindered rotation about the N-N bond. Separation was achieved using adsorption, reversed-phase, and ion-exchange modes. For the nitroso-amino acids, a shift in the equilibrium conformer concentration was observed with changes in pH."}
{"id": "PMID:234975", "title": "Aromatization of androgens by human abdominal and breast fat tissue.", "content": "The ability of human abdominal, breast and axillary fat to convert androgens into estrogens was investigated by incubating labeled substrates in the presence of NADPH with a variety of cell preparations. The incubation products were subjected to phenolic partition, paper chromatography, methyl-ether formation, repeat chromatography and crystallization with cold carrier reference standards to constant specific activity. Androstenedione was converted to estrone and, to a lesser extent, to 17beta-estradiol by crude homogenates, minces, fat-free particulate fractions (1,000-100,000 time g) and isolated fat cells obtained from abdominal, breast or axillary fat. Testosterone was found to be aromatized as actively as androstenedione, but inthis case more 17 beta-estrodiol was formed than estrone. 19-Hydroxyandrostenedione-2 also served as substrate, givingresults similar to those obtained with androstenedione. Fat tissue obtained from cancerous breasts was found to be as active as normal breast fat (1-4 pg/g fat/90 min) and within the range found for abdominal fat (1-27 pg/g fat/90 min). In each case in which axillary fat was compared to breast fat from the same subject, the activity of the axillary fat was 5 to 10 times higher. The results indicate a possible role of adipose tissue as a significant extra-gonadal source of estrogens.", "contents": "Aromatization of androgens by human abdominal and breast fat tissue. The ability of human abdominal, breast and axillary fat to convert androgens into estrogens was investigated by incubating labeled substrates in the presence of NADPH with a variety of cell preparations. The incubation products were subjected to phenolic partition, paper chromatography, methyl-ether formation, repeat chromatography and crystallization with cold carrier reference standards to constant specific activity. Androstenedione was converted to estrone and, to a lesser extent, to 17beta-estradiol by crude homogenates, minces, fat-free particulate fractions (1,000-100,000 time g) and isolated fat cells obtained from abdominal, breast or axillary fat. Testosterone was found to be aromatized as actively as androstenedione, but inthis case more 17 beta-estrodiol was formed than estrone. 19-Hydroxyandrostenedione-2 also served as substrate, givingresults similar to those obtained with androstenedione. Fat tissue obtained from cancerous breasts was found to be as active as normal breast fat (1-4 pg/g fat/90 min) and within the range found for abdominal fat (1-27 pg/g fat/90 min). In each case in which axillary fat was compared to breast fat from the same subject, the activity of the axillary fat was 5 to 10 times higher. The results indicate a possible role of adipose tissue as a significant extra-gonadal source of estrogens."}
{"id": "PMID:234976", "title": "Chromatographic heterogeneity of insulin extracted from insulomas.", "content": "On gel filtration of acid-ethanol extracts from three pancreatic beta-cell adenomas 1.4% to 1.8% of total immunomeasurable insulin (IMI) eluted ahead of proinsulin. This high molecular IMI was resolved into three components. The presence of urea in the dilute acetic acid solutions of extracted tumor tissue did not influence the pattern of gel filtration. High molecular IMI dissolved in dilute acetic acid showed to be stable if immediately rechromatographed, but a partial dissociation to insulinlike and proinsulinlike components (ILC and PLC) was found if rechromatography was performed after 48 h of incubation. Mainly ILC and PLC were found on rechromatography provided high molecular IMI was dissolved and incubated briefly in 0.04M phosphate buffer, pH 7.4. It proved improbable that the proteolytic action of some protein being extracted with the hormones caused a splitting of high molecular IMI at pH 7.4. We conclude from our findings that the components of high molecular IMI are not precursors of proinsulin and insulin but are either self-associated products of the hormones or associations of insulin and proinsulin to other proteins extracted from insuloma tissue.", "contents": "Chromatographic heterogeneity of insulin extracted from insulomas. On gel filtration of acid-ethanol extracts from three pancreatic beta-cell adenomas 1.4% to 1.8% of total immunomeasurable insulin (IMI) eluted ahead of proinsulin. This high molecular IMI was resolved into three components. The presence of urea in the dilute acetic acid solutions of extracted tumor tissue did not influence the pattern of gel filtration. High molecular IMI dissolved in dilute acetic acid showed to be stable if immediately rechromatographed, but a partial dissociation to insulinlike and proinsulinlike components (ILC and PLC) was found if rechromatography was performed after 48 h of incubation. Mainly ILC and PLC were found on rechromatography provided high molecular IMI was dissolved and incubated briefly in 0.04M phosphate buffer, pH 7.4. It proved improbable that the proteolytic action of some protein being extracted with the hormones caused a splitting of high molecular IMI at pH 7.4. We conclude from our findings that the components of high molecular IMI are not precursors of proinsulin and insulin but are either self-associated products of the hormones or associations of insulin and proinsulin to other proteins extracted from insuloma tissue."}
{"id": "PMID:234977", "title": "Studies on the human testis. VI. NADH-linked reactions of microsomal steroid 20alpha-and 20beta-hydroxysteroid dehydrogenase and 17alpha-hydroxylase.", "content": "NADH-linked 20alpha- and 20beta-hydroxysteroid dehydrogenase and 17alpha-hydroxylase activities were demonstrated in the microsomal fraction of the human testis. The microsomal 20alpha-hydroxysteroid dehydrogenase showed substrate affinity to pregnenolone and progesterone and not to 17alpha-hydroxyprogesterone and preferred NADH to NADPH as a hydrogen donor. In the presence of NADH, the optimal pH for the enzyme was 7.7 and the apparent Michaelis constants of the enzyme for progesterone and pregnenolone at 37 C and pH 7.4 were 6.9-7.1 X 10-6M and in the order of 10-5M, respectively, 17alpha, 20beta-Dihydroxypregn-4-en-3-one was the only significant metabolite produced from 17alpha-hydroxyprogesterone by microsomal fraction of the human testis in the presence of NADH. The apparent Michaelis constant of microsomal 20beta-hydroxysteroid dehydrogenase for 17alpha-hydroxyprogesterone in the presence of NADH was in the order of 10-5M at 37 C and pH 7.4. The microsomal 17alpha-hydroxylase catalyzed the metabolism of pregnenolone and progesterone at a similar rate in the presence of NADH. The optimal pH and the apparent Michaelis constant at 37 C and pH 7.4 of the NADH-linked reaction of 17alpha-hydroxylase for progesterone were 7.7 and 5.3-5.4 X 10-7M, resepctively. The NADH-linked enzyme activity for progesterone was competitively inhibited by both pregn-5-ene-3beta, 20alpha-diol (inhibition constant: 1.7 X 10-7M) and 20alpha-hydroxypregn-4-en-3 one (inhibition constant: 6.6 X 10-7M), and was resistant to poor oxygen supply during incubation. The results indicate that the microsomal 20alpha-hydroxysteroid dehydrogenase is a different enzyme from the one in the soluble fraction of the human testis and that microsomal 17alpha-hydroxylase in the human testis is activated by NADH as well as NADPH.", "contents": "Studies on the human testis. VI. NADH-linked reactions of microsomal steroid 20alpha-and 20beta-hydroxysteroid dehydrogenase and 17alpha-hydroxylase. NADH-linked 20alpha- and 20beta-hydroxysteroid dehydrogenase and 17alpha-hydroxylase activities were demonstrated in the microsomal fraction of the human testis. The microsomal 20alpha-hydroxysteroid dehydrogenase showed substrate affinity to pregnenolone and progesterone and not to 17alpha-hydroxyprogesterone and preferred NADH to NADPH as a hydrogen donor. In the presence of NADH, the optimal pH for the enzyme was 7.7 and the apparent Michaelis constants of the enzyme for progesterone and pregnenolone at 37 C and pH 7.4 were 6.9-7.1 X 10-6M and in the order of 10-5M, respectively, 17alpha, 20beta-Dihydroxypregn-4-en-3-one was the only significant metabolite produced from 17alpha-hydroxyprogesterone by microsomal fraction of the human testis in the presence of NADH. The apparent Michaelis constant of microsomal 20beta-hydroxysteroid dehydrogenase for 17alpha-hydroxyprogesterone in the presence of NADH was in the order of 10-5M at 37 C and pH 7.4. The microsomal 17alpha-hydroxylase catalyzed the metabolism of pregnenolone and progesterone at a similar rate in the presence of NADH. The optimal pH and the apparent Michaelis constant at 37 C and pH 7.4 of the NADH-linked reaction of 17alpha-hydroxylase for progesterone were 7.7 and 5.3-5.4 X 10-7M, resepctively. The NADH-linked enzyme activity for progesterone was competitively inhibited by both pregn-5-ene-3beta, 20alpha-diol (inhibition constant: 1.7 X 10-7M) and 20alpha-hydroxypregn-4-en-3 one (inhibition constant: 6.6 X 10-7M), and was resistant to poor oxygen supply during incubation. The results indicate that the microsomal 20alpha-hydroxysteroid dehydrogenase is a different enzyme from the one in the soluble fraction of the human testis and that microsomal 17alpha-hydroxylase in the human testis is activated by NADH as well as NADPH."}
{"id": "PMID:234978", "title": "Role of adrenergic stimuli in parathyroid hormone secretion in man.", "content": "The role of adrenergic stimuli in the secretion of parathyroid hormone (PTH) in man was evaluated. Intradermal injections of isoproterenol, 0.15 mg, or epinephrine, 0.3 mg, caused significant prompt increases in serum PTH levels. These increases were not accompanied by any changes in serum calcium (Ca) during the period of observation. Phenylephrine, 1.5 mg, intradermally, did not cause any significant changes in serum PTH or serum Ca. Propranolol infusion alone significantly inhibited the basal secretion of PTH. This inhibition by propranolol was overcome by isoproterenol administration. The results indicate that 1) beta adrenergic agents increase PTH secretion whereas alpha adrenergic agents have no effect, 2) beta adrenergic stimuli probably play an important physiological role in basal PTH secretion in man.", "contents": "Role of adrenergic stimuli in parathyroid hormone secretion in man. The role of adrenergic stimuli in the secretion of parathyroid hormone (PTH) in man was evaluated. Intradermal injections of isoproterenol, 0.15 mg, or epinephrine, 0.3 mg, caused significant prompt increases in serum PTH levels. These increases were not accompanied by any changes in serum calcium (Ca) during the period of observation. Phenylephrine, 1.5 mg, intradermally, did not cause any significant changes in serum PTH or serum Ca. Propranolol infusion alone significantly inhibited the basal secretion of PTH. This inhibition by propranolol was overcome by isoproterenol administration. The results indicate that 1) beta adrenergic agents increase PTH secretion whereas alpha adrenergic agents have no effect, 2) beta adrenergic stimuli probably play an important physiological role in basal PTH secretion in man."}
{"id": "PMID:234979", "title": "Action of (1-des(aspartic acid), 8-isoleucine) angiotensin II upon the pressor and steroidogenic activity of angiotensin II.", "content": "The vascular and steroidogenic responses to (1-Sarcosine, 8-Isoleucine)-, and to (1-Des (Aspartic acid), 8-Isoleucine) angiotensin II were compared in bilaterally nephrectomized, ACTH-suppressed dogs receiving constant infusions of angiotensin II. Aldosterone secretion rate was significantly inhibited by pretreatment with 200 ng/Kg/min of the heptapeptide, (1-Des(Aspartic acid), 8-Isoleucine) ang II, but not by similar doses of the octapeptide, (1-Sarcosine, 8-Isoleucine) ang II. In contrast, the pressor action of ang II was unaffected by (1-Des (Aspartic acid), 8-Isoleucine) ang II though significant inhibition occurred with relatively small doses of (1-Sarcosine, 8-Isoleucine) ang II. This study suggests that: (a) angiotensin receptors in adrenal cortex and vascular smooth muscle are functionally different, and (b) (1-Des(Aspartic acid),8-Isoleucine) angiotensin II is a specific antagonist of steroidogenic effect of ang II.", "contents": "Action of (1-des(aspartic acid), 8-isoleucine) angiotensin II upon the pressor and steroidogenic activity of angiotensin II. The vascular and steroidogenic responses to (1-Sarcosine, 8-Isoleucine)-, and to (1-Des (Aspartic acid), 8-Isoleucine) angiotensin II were compared in bilaterally nephrectomized, ACTH-suppressed dogs receiving constant infusions of angiotensin II. Aldosterone secretion rate was significantly inhibited by pretreatment with 200 ng/Kg/min of the heptapeptide, (1-Des(Aspartic acid), 8-Isoleucine) ang II, but not by similar doses of the octapeptide, (1-Sarcosine, 8-Isoleucine) ang II. In contrast, the pressor action of ang II was unaffected by (1-Des (Aspartic acid), 8-Isoleucine) ang II though significant inhibition occurred with relatively small doses of (1-Sarcosine, 8-Isoleucine) ang II. This study suggests that: (a) angiotensin receptors in adrenal cortex and vascular smooth muscle are functionally different, and (b) (1-Des(Aspartic acid),8-Isoleucine) angiotensin II is a specific antagonist of steroidogenic effect of ang II."}
{"id": "PMID:234980", "title": "Hemoglobin Syracuse (alpha2beta2-143(H21)His leads to Pro), a new high-affinity variant detected by special electrophoretic methods. Observations on the auto-oxidation of normal and variant hemoglobins.", "content": "Family members from four generations were found to have polycythemia and increased whole blood O2 affinity (P50; 11 mm Hg; normal, 27 mm Hg). No abnormal hemoglobin bands were seen after electrophoresis on starch gel at pH 8.6 or agar gel at pH 6.0. Analysis of the oxygenated hemolysate by isoelectric focusing on polyacrylamide gel revealed two closely spaced bands. When deoxygenated hemolysate was analyzed in oxygen-free gels, the two components were more widely separated. About 40% of the patient's hemoglobin focused at a more acid pH than hemoglobin A, indicating a hemoglobin variant with impaired Bohr effect. Chromatography of globin in 8 M urea revealed two beta-chain peaks, the first of which was eluted at a lower buffer molarity than normal beta chain. Fingerprints of tryptic digests of the aminoethylated chains were done on silica gel thin-layer plates. Tp 14 from the abnormal beta chain had slower electrophoretic mobility and a greater Rf value. Amino acid analyses of this peptide gave values identical with those of betaTp 14, except that it contained one proline residue and no histidine. Since the one His in betaTp 14 is in position 143, hemoglobin Syracuse in alpha2beta2-143 His leads to Pro. Native Hb Syracuse could be separated from hemoglobin A on a carboxymethylcellulose column. The inclusion of 0.1 mM EDTA in the preparative buffers proved very useful in reducing the formation of methemoglobin. Oxygen equilibria of purified hemoglobin Syracuse showed high oxygen affinity (P50 value 12% that of hemoglobin A) and lack of cooperativity between subunits (Hill's n equals 1.1). The alkaline Bohr effect was about half that of hemoglobin A. The proline substitution at betaH21 disrupts the helical configuration and probably prevents the formation of salt bonds that are important in stabilizing the deoxy structure and contribute to the alkaline Bohr effect. Since beta143 His is a binding site for 2,3-diphosphoglycerate (2,3-DPG), it is not suprising that hemoglobin Syracuse had markedly impaired reactivity with 2,3-DPG. Hemoglobin Syracuse auto-oxidized more slowly than hemoglobin A, probably reflecting a slower rate of dissociation of oxygen from fully liganded hemoglobin.", "contents": "Hemoglobin Syracuse (alpha2beta2-143(H21)His leads to Pro), a new high-affinity variant detected by special electrophoretic methods. Observations on the auto-oxidation of normal and variant hemoglobins. Family members from four generations were found to have polycythemia and increased whole blood O2 affinity (P50; 11 mm Hg; normal, 27 mm Hg). No abnormal hemoglobin bands were seen after electrophoresis on starch gel at pH 8.6 or agar gel at pH 6.0. Analysis of the oxygenated hemolysate by isoelectric focusing on polyacrylamide gel revealed two closely spaced bands. When deoxygenated hemolysate was analyzed in oxygen-free gels, the two components were more widely separated. About 40% of the patient's hemoglobin focused at a more acid pH than hemoglobin A, indicating a hemoglobin variant with impaired Bohr effect. Chromatography of globin in 8 M urea revealed two beta-chain peaks, the first of which was eluted at a lower buffer molarity than normal beta chain. Fingerprints of tryptic digests of the aminoethylated chains were done on silica gel thin-layer plates. Tp 14 from the abnormal beta chain had slower electrophoretic mobility and a greater Rf value. Amino acid analyses of this peptide gave values identical with those of betaTp 14, except that it contained one proline residue and no histidine. Since the one His in betaTp 14 is in position 143, hemoglobin Syracuse in alpha2beta2-143 His leads to Pro. Native Hb Syracuse could be separated from hemoglobin A on a carboxymethylcellulose column. The inclusion of 0.1 mM EDTA in the preparative buffers proved very useful in reducing the formation of methemoglobin. Oxygen equilibria of purified hemoglobin Syracuse showed high oxygen affinity (P50 value 12% that of hemoglobin A) and lack of cooperativity between subunits (Hill's n equals 1.1). The alkaline Bohr effect was about half that of hemoglobin A. The proline substitution at betaH21 disrupts the helical configuration and probably prevents the formation of salt bonds that are important in stabilizing the deoxy structure and contribute to the alkaline Bohr effect. Since beta143 His is a binding site for 2,3-diphosphoglycerate (2,3-DPG), it is not suprising that hemoglobin Syracuse had markedly impaired reactivity with 2,3-DPG. Hemoglobin Syracuse auto-oxidized more slowly than hemoglobin A, probably reflecting a slower rate of dissociation of oxygen from fully liganded hemoglobin."}
{"id": "PMID:234981", "title": "The effect of an H2-receptor antagonist on food-stimulated acid secretion, serum gastrin, and gastric emptying in patients with duodenal ulcers. Comparison with an anticholinergic drug.", "content": "The purpose of the present series of experiments was to measure and compare the effects of an anticholinergic drug (isopropamide) and an antagonist of the histamine H2 receptor (metiamide) on food-stimulated acid secretion. Patients with duodenal ulcers were stimulated by a steak meal, and acid secretion was measured by in vivo intragastric titration. The largest dose of isopropamide that can be taken clinically without producing intolerable side effects (maximum tolerated dose) suppressed food-stimulated acid secretion by 35%. By contrast, metiamide in a 400-mg dose produced no side effects and almost completely abolished food-stimulated acid secretion. A dose-response curve revealed that a 50-mg dose of metiamide was required to suppress food-stimulated acid secretion by 50%. Further studies showed that metiamide and isopropamide are additive in suppressing food-stimulated acid secretion, and that metiamide has no effect on serum gastrin concentration or on gastric emptying.", "contents": "The effect of an H2-receptor antagonist on food-stimulated acid secretion, serum gastrin, and gastric emptying in patients with duodenal ulcers. Comparison with an anticholinergic drug. The purpose of the present series of experiments was to measure and compare the effects of an anticholinergic drug (isopropamide) and an antagonist of the histamine H2 receptor (metiamide) on food-stimulated acid secretion. Patients with duodenal ulcers were stimulated by a steak meal, and acid secretion was measured by in vivo intragastric titration. The largest dose of isopropamide that can be taken clinically without producing intolerable side effects (maximum tolerated dose) suppressed food-stimulated acid secretion by 35%. By contrast, metiamide in a 400-mg dose produced no side effects and almost completely abolished food-stimulated acid secretion. A dose-response curve revealed that a 50-mg dose of metiamide was required to suppress food-stimulated acid secretion by 50%. Further studies showed that metiamide and isopropamide are additive in suppressing food-stimulated acid secretion, and that metiamide has no effect on serum gastrin concentration or on gastric emptying."}
{"id": "PMID:234982", "title": "Laser fusion of selected dental casting alloys.", "content": "Laser-fused precious, nonprecious, and mixed metal welds were investigated for optimum weld energy requirement as determined by tensile strength tests. These strengths were compared to soldered unions. Laser fusion is as good as, or better than, unions created by conventional dental joining methods.", "contents": "Laser fusion of selected dental casting alloys. Laser-fused precious, nonprecious, and mixed metal welds were investigated for optimum weld energy requirement as determined by tensile strength tests. These strengths were compared to soldered unions. Laser fusion is as good as, or better than, unions created by conventional dental joining methods."}
{"id": "PMID:234983", "title": "Effects of phosphates in acid-containing beverages on tooth erosion.", "content": "Rat studies demonstrated that low-pH powdered beverage mixes containing monocalcium phosphate caused less molar erosion than reconstituted frozen orange juice and grape juice when these beverages were consumed at excessive levels. A number of sodium phosphate supplements in low-pH beverages were not as effective as monocalcium phosphate in preventing molar erosion. Total acidity or pH values of the beverages could not be used with reliability to predict their potential to cause molar erosion.", "contents": "Effects of phosphates in acid-containing beverages on tooth erosion. Rat studies demonstrated that low-pH powdered beverage mixes containing monocalcium phosphate caused less molar erosion than reconstituted frozen orange juice and grape juice when these beverages were consumed at excessive levels. A number of sodium phosphate supplements in low-pH beverages were not as effective as monocalcium phosphate in preventing molar erosion. Total acidity or pH values of the beverages could not be used with reliability to predict their potential to cause molar erosion."}
{"id": "PMID:234984", "title": "Studies of fluorapatite: II. The solubility behavior.", "content": "The solubility product of fluorapatite has been determined by equilibrating a very pure mineral specimen in KCl solutions at ionic strengths up to 0.1. At pH's less than 5.0 to 6.0 the solubility product of fluorite, and not that of fluorapatite, is the governing principle under the experimental conditions used.", "contents": "Studies of fluorapatite: II. The solubility behavior. The solubility product of fluorapatite has been determined by equilibrating a very pure mineral specimen in KCl solutions at ionic strengths up to 0.1. At pH's less than 5.0 to 6.0 the solubility product of fluorite, and not that of fluorapatite, is the governing principle under the experimental conditions used."}
{"id": "PMID:234988", "title": "Cellular localization of tyrosine hydroxylase by immunohistochemistry.", "content": "The enzyme tyrosine hydroxylase (TH) was immunohistochemically localized by the peroxidase-antiperoxidase method in rat to chromaffin cells of the adrenal medulla, large neurons and small darkly staining cells of the superior cervical ganglia and noradrenergic and dopaminergic neurons in brain. As compared with the conjugated peroxidase or immunofluorescence techniques, the peroxidase-antiperoxidase method gave the most selective and specific cytoplasmic localization of TH antisera in every tissue examined. The peroxidase staining with the TH antisera was more intense in dopaminergic than in noradrenergic neurons of the central nervous system. While TH was visualized in cell bodies of both dopaminergic and noradrenergic neurons, it could only be detected in axons and terminals in the dopaminergic system. The perikarya of noradrenergic neurons could be distinguished from dopaminergic neurons by the immunohistochemical demonstration of the enzyme dopamine-beta-hydroxylase only in the former.", "contents": "Cellular localization of tyrosine hydroxylase by immunohistochemistry. The enzyme tyrosine hydroxylase (TH) was immunohistochemically localized by the peroxidase-antiperoxidase method in rat to chromaffin cells of the adrenal medulla, large neurons and small darkly staining cells of the superior cervical ganglia and noradrenergic and dopaminergic neurons in brain. As compared with the conjugated peroxidase or immunofluorescence techniques, the peroxidase-antiperoxidase method gave the most selective and specific cytoplasmic localization of TH antisera in every tissue examined. The peroxidase staining with the TH antisera was more intense in dopaminergic than in noradrenergic neurons of the central nervous system. While TH was visualized in cell bodies of both dopaminergic and noradrenergic neurons, it could only be detected in axons and terminals in the dopaminergic system. The perikarya of noradrenergic neurons could be distinguished from dopaminergic neurons by the immunohistochemical demonstration of the enzyme dopamine-beta-hydroxylase only in the former."}
{"id": "PMID:234985", "title": "Computer-facilitated nutritional analysis.", "content": "A seven-day dietary analysis of 59 students in the dental health profession indicated that their nutrient consumption was generally adequate. A dental health examination indicated excellent oral hygiene. Nevertheless, many students were deficient in specific nutrient categories. Results suggested that computerized nutritional analysis techniques have general applicability in dental practice and epidemiological testing.", "contents": "Computer-facilitated nutritional analysis. A seven-day dietary analysis of 59 students in the dental health profession indicated that their nutrient consumption was generally adequate. A dental health examination indicated excellent oral hygiene. Nevertheless, many students were deficient in specific nutrient categories. Results suggested that computerized nutritional analysis techniques have general applicability in dental practice and epidemiological testing."}
{"id": "PMID:234989", "title": "Studies on the specificity of autoantibodies produced in systemic graft-vs-host disease.", "content": "Anti-erythrocyte antibodies were found in serum and on RBC of F-1 hybrid hamsters afflicted with systemic graft-vs-host (GVH) disease. These antibodies were shown to be reactive with antigenic determinants unique to hamster erythrocytes compared to heterologous erythrocytes and to non-erythrocytic hamster tissues. They fulfilled the criteria for true autoantibodies by failing to discriminate strain specificities among the domestically maintained isogenic hamster lines that were tested. It is suggested that the excessive production of these antibodies results from the allogeneic effect by which donor T-lymphocytes attack host B lymphocytes and stimulate heretofore quiescent self-reactive clones. Moreover,it is proposed that these autoantibodies can function as enhancing antibodies and subvert continued progression of GVH disease. In this regard, they resemble antibodies directed at allogeneic transplantation antigens that have been shown to attenuate and abort GVH processes.", "contents": "Studies on the specificity of autoantibodies produced in systemic graft-vs-host disease. Anti-erythrocyte antibodies were found in serum and on RBC of F-1 hybrid hamsters afflicted with systemic graft-vs-host (GVH) disease. These antibodies were shown to be reactive with antigenic determinants unique to hamster erythrocytes compared to heterologous erythrocytes and to non-erythrocytic hamster tissues. They fulfilled the criteria for true autoantibodies by failing to discriminate strain specificities among the domestically maintained isogenic hamster lines that were tested. It is suggested that the excessive production of these antibodies results from the allogeneic effect by which donor T-lymphocytes attack host B lymphocytes and stimulate heretofore quiescent self-reactive clones. Moreover,it is proposed that these autoantibodies can function as enhancing antibodies and subvert continued progression of GVH disease. In this regard, they resemble antibodies directed at allogeneic transplantation antigens that have been shown to attenuate and abort GVH processes."}
{"id": "PMID:234990", "title": "Detection of antibodies to mycobacterium tuberculosis by solid phase radioimmunoassay.", "content": "The sandwich solid phase radioimmunoassay procedure has been adapted to the serological diagnosis of tuberculosis by the use of disposable plastic haemagglutination trays in which the wells were sensitized with soluble mycobacterial antigen and the subsequent uptake of globulin from test sera detected with radioiodinated antiglobulin. The influence of time and temperature of the incubation stages, pH, washing times, drying and the efficiency of various non-specific blocking agents have been studied. In an initial survey carried out on 319 sera the results obtained showed a good correlation with the presence or absence of established tuberculous infection.", "contents": "Detection of antibodies to mycobacterium tuberculosis by solid phase radioimmunoassay. The sandwich solid phase radioimmunoassay procedure has been adapted to the serological diagnosis of tuberculosis by the use of disposable plastic haemagglutination trays in which the wells were sensitized with soluble mycobacterial antigen and the subsequent uptake of globulin from test sera detected with radioiodinated antiglobulin. The influence of time and temperature of the incubation stages, pH, washing times, drying and the efficiency of various non-specific blocking agents have been studied. In an initial survey carried out on 319 sera the results obtained showed a good correlation with the presence or absence of established tuberculous infection."}
{"id": "PMID:234991", "title": "Aryl hydrocarbon (benzo[a]pyrene) hydroxylase: a mixed-function oxygenase in mouse skin.", "content": "Mouse skin contains aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity which is inducible by aromatic polycyclic hydrocarbons and benzoflavones.  The duration and magnitude of induction, but not the initial kinetics, are dependent on the inducer dose.  The cutaneous hydroxylase activity is inhibited by carbon monoxide and requires the presence of NADPH, indicating that the enzyme is one of the mixed-function oxygenases.  The highest enzyme activity was found in the superficial layer of skin which contains the sebaceous glands and the upper pilary canals.  Enzyme activities were intermediate in the epidermis and lowest in the deeper dermal layers.", "contents": "Aryl hydrocarbon (benzo[a]pyrene) hydroxylase: a mixed-function oxygenase in mouse skin. Mouse skin contains aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity which is inducible by aromatic polycyclic hydrocarbons and benzoflavones.  The duration and magnitude of induction, but not the initial kinetics, are dependent on the inducer dose.  The cutaneous hydroxylase activity is inhibited by carbon monoxide and requires the presence of NADPH, indicating that the enzyme is one of the mixed-function oxygenases.  The highest enzyme activity was found in the superficial layer of skin which contains the sebaceous glands and the upper pilary canals.  Enzyme activities were intermediate in the epidermis and lowest in the deeper dermal layers."}
{"id": "PMID:234993", "title": "Role of urease in pyelonephritis resulting from urinary tract infection with Proteus.", "content": "The role of urease in induction of pyelonephritis was studied by treatment of proteus-infected rats with acetohydroxamic acid, a potent inhibitor of urease. Infection was produced by introduction of Proteus mirabilis into the bladder along with a zinc disk. Controls were treated identically but received no acetohydroxamic acid. The number of bacteria per milliliter of urine was the same in both groups. The number of bacteria in the kidneys and the extent of renal damage was much greater in controls. Common enterobacteraceal antigen was not detected in the renal parenchyma of rats treated with acetohydroxamic acid. Treatment with acetohydroxamic acid thus prevented invasion of and damage to kidney tissue without reduction of urinary infection. Thus new evidence was found that the invasive properties of Proteus in the urinary tract are dependent on alkalinization of urine by urease and the resulting damage to the renal epithelium.", "contents": "Role of urease in pyelonephritis resulting from urinary tract infection with Proteus. The role of urease in induction of pyelonephritis was studied by treatment of proteus-infected rats with acetohydroxamic acid, a potent inhibitor of urease. Infection was produced by introduction of Proteus mirabilis into the bladder along with a zinc disk. Controls were treated identically but received no acetohydroxamic acid. The number of bacteria per milliliter of urine was the same in both groups. The number of bacteria in the kidneys and the extent of renal damage was much greater in controls. Common enterobacteraceal antigen was not detected in the renal parenchyma of rats treated with acetohydroxamic acid. Treatment with acetohydroxamic acid thus prevented invasion of and damage to kidney tissue without reduction of urinary infection. Thus new evidence was found that the invasive properties of Proteus in the urinary tract are dependent on alkalinization of urine by urease and the resulting damage to the renal epithelium."}
{"id": "PMID:234995", "title": "Kinetics of hemodiafiltration. II. Clinical characterization of a new blood cleansing modality.", "content": "Hemodiafiltration, a process in which whole blood is first diluted with a physiologic electrolyte solution and then ultrafiltered across a membrane to convectively remove solutes and excess water, has been applied clinically for the first time. Six-hour hemodiafiltration with a 1.6 m.2 hollow-fiber ultrafilter was applied intermittently to an anephric patient as an alternative to 6-hour hemodialysis using a 1.45 m.2 coli. A quantitative basis for evaluating clinical hemodiafiltration kinetics was developed, and the results were compared with data from prototype devices. With blood, diluting fluid, and ultrafiltrate flow rates of 200 ml. per minute, removal rates of urea and creatinine by both hemodiafiltration and dialysis were comparable, but for solutes of larger molecular weight (uric acid, phosphate, and inulin) removal rate was significantly greater for hemodiafiltration. The observed ultrafiltrate flux was similar to values predicted from in vitro studies. With the present membrane formulation the measured sieving coefficients for inulin, creatinine, and urea were not significantly different from one, and whole blood clearances for these solutes were 117, 108, and 101 ml. per minute, respectively. This solute clearance pattern is very similar to the human kidney and in sharp contrast to standard coil hemodialysis.", "contents": "Kinetics of hemodiafiltration. II. Clinical characterization of a new blood cleansing modality. Hemodiafiltration, a process in which whole blood is first diluted with a physiologic electrolyte solution and then ultrafiltered across a membrane to convectively remove solutes and excess water, has been applied clinically for the first time. Six-hour hemodiafiltration with a 1.6 m.2 hollow-fiber ultrafilter was applied intermittently to an anephric patient as an alternative to 6-hour hemodialysis using a 1.45 m.2 coli. A quantitative basis for evaluating clinical hemodiafiltration kinetics was developed, and the results were compared with data from prototype devices. With blood, diluting fluid, and ultrafiltrate flow rates of 200 ml. per minute, removal rates of urea and creatinine by both hemodiafiltration and dialysis were comparable, but for solutes of larger molecular weight (uric acid, phosphate, and inulin) removal rate was significantly greater for hemodiafiltration. The observed ultrafiltrate flux was similar to values predicted from in vitro studies. With the present membrane formulation the measured sieving coefficients for inulin, creatinine, and urea were not significantly different from one, and whole blood clearances for these solutes were 117, 108, and 101 ml. per minute, respectively. This solute clearance pattern is very similar to the human kidney and in sharp contrast to standard coil hemodialysis."}
{"id": "PMID:234996", "title": "Alteration of factor VII activity by activated Fletcher factor (a plasma kallikrein): a potential link between the intrinsic and extrinsic blood-clotting systems.", "content": "Although surface contact is known to accelerate the one-stage prothrombin time of human plasma through the participation of Hageman factor (factor XII) and factor VII, it has not been clear whether Hageman factor interacts with factor VII directly or indirectly. Recently, Gj\u00f8nnaess reported experiments suggesting that plasma kallikrein was an intermediate between Hageman factor and factor VII. The present study was undertaken to elucidate the interaction of plasma kallikrein and factor VII. Incubation of Fletcher-trait plasma (deficient in a plasma prekallikrein) with kaolin at 0 degrees C. did not induce shortening of the Thrombotest time or enhancement of factor VII activity, in contrast to studies of normal plasma. Monospecific rabbit antiserum against plasma kallikrein blocked the shortening of the Thrombotest time of normal plasma brought about by kaolin. Purified Hageman factor fragments (prekallikrein activator) induced an increase in factor VII activity in normal or Hageman-trait plasma, but not in Fletcher-trait plasma. A purified plasma kallikrein preparation enhanced factor VII activity in all plasmas, including that of Fletcher-trait plasma. The effect of the kallikrein preparation was blocked by soybean trypsin inhibitor, Trasylol, or rabbit antiserum against kallikrein, but not by lima bean trypsin inhibitor or antiserum against Hageman factor. The activity of partially purified factor VII was enhanced by purified kallikrein in the presence, but not in the absence of factor VII-deficient plasma. These results further support the idea that the enhancement of factor VII activity by surface contact is via Hageman factor and plasma kallikrein, suggesting a possible link between the intrinsic and extrinsic pathway of blood clotting. The significance of this phenomenon in hemostasis in vivo remains to be elucidated.", "contents": "Alteration of factor VII activity by activated Fletcher factor (a plasma kallikrein): a potential link between the intrinsic and extrinsic blood-clotting systems. Although surface contact is known to accelerate the one-stage prothrombin time of human plasma through the participation of Hageman factor (factor XII) and factor VII, it has not been clear whether Hageman factor interacts with factor VII directly or indirectly. Recently, Gj\u00f8nnaess reported experiments suggesting that plasma kallikrein was an intermediate between Hageman factor and factor VII. The present study was undertaken to elucidate the interaction of plasma kallikrein and factor VII. Incubation of Fletcher-trait plasma (deficient in a plasma prekallikrein) with kaolin at 0 degrees C. did not induce shortening of the Thrombotest time or enhancement of factor VII activity, in contrast to studies of normal plasma. Monospecific rabbit antiserum against plasma kallikrein blocked the shortening of the Thrombotest time of normal plasma brought about by kaolin. Purified Hageman factor fragments (prekallikrein activator) induced an increase in factor VII activity in normal or Hageman-trait plasma, but not in Fletcher-trait plasma. A purified plasma kallikrein preparation enhanced factor VII activity in all plasmas, including that of Fletcher-trait plasma. The effect of the kallikrein preparation was blocked by soybean trypsin inhibitor, Trasylol, or rabbit antiserum against kallikrein, but not by lima bean trypsin inhibitor or antiserum against Hageman factor. The activity of partially purified factor VII was enhanced by purified kallikrein in the presence, but not in the absence of factor VII-deficient plasma. These results further support the idea that the enhancement of factor VII activity by surface contact is via Hageman factor and plasma kallikrein, suggesting a possible link between the intrinsic and extrinsic pathway of blood clotting. The significance of this phenomenon in hemostasis in vivo remains to be elucidated."}
{"id": "PMID:234997", "title": "The effect of pH on radioimmunoassay of LH and FSH.", "content": "Freezing and thawing of human serum produces alkaline changes in the pH. Weak buffers were of insufficient capacity to compensate for these pH changes. Thus the effect of serum pH on modified solid-phase and double-antibody radioimmunoassay (RIA) of LH and FSH was studied. Pooled postmenopausal serum standardized against the Second International Reference Preparation of Human Menopausal Urinary Gonadotropon was used as a laboratory standard. In the solid phase RIA for LH and FSH, slopes with the greatest maximum binding were obtained at pH 6.4, whereas for the double-antibody method best results were obtained at pH 8.0. Since there is individual variation in the pH of various serum samples, different values will be obtained from samples containing the same amount of hormone. It is sum samples be standardized by the use of buffers with the capacity to keep the pH of the serum constant and that serum standards be dialyzed.", "contents": "The effect of pH on radioimmunoassay of LH and FSH. Freezing and thawing of human serum produces alkaline changes in the pH. Weak buffers were of insufficient capacity to compensate for these pH changes. Thus the effect of serum pH on modified solid-phase and double-antibody radioimmunoassay (RIA) of LH and FSH was studied. Pooled postmenopausal serum standardized against the Second International Reference Preparation of Human Menopausal Urinary Gonadotropon was used as a laboratory standard. In the solid phase RIA for LH and FSH, slopes with the greatest maximum binding were obtained at pH 6.4, whereas for the double-antibody method best results were obtained at pH 8.0. Since there is individual variation in the pH of various serum samples, different values will be obtained from samples containing the same amount of hormone. It is sum samples be standardized by the use of buffers with the capacity to keep the pH of the serum constant and that serum standards be dialyzed."}
{"id": "PMID:234998", "title": "Serum levels and biochemical characterization of oestradiol-17 beta dehydrogenase in umbilical cord blood.", "content": "The properties of the enzyme oestradiol-17 beta dehydrogenase from human umbilical cord serum have beem compared with those of oestradiol-17 beta dehydrogenase present in the maternal peripheral blood. On the basis of studies on stability, specificity, optimum pH, rate of enzymic reaction and Km determinations it can be concluded that oestradiol-17 beta dehydrogenase in the umbilical cord arteries has an activity between 5 and 15 times higher than in the umbilical cord vein and about 65% of the activity of the enzyme present in the maternal peripheral blood. The present results strongly suggest that in pregnancy the enzyme oestradiol-17 beta dehydrogenase is elaborated not only by the placenta but also by the foetus.", "contents": "Serum levels and biochemical characterization of oestradiol-17 beta dehydrogenase in umbilical cord blood. The properties of the enzyme oestradiol-17 beta dehydrogenase from human umbilical cord serum have beem compared with those of oestradiol-17 beta dehydrogenase present in the maternal peripheral blood. On the basis of studies on stability, specificity, optimum pH, rate of enzymic reaction and Km determinations it can be concluded that oestradiol-17 beta dehydrogenase in the umbilical cord arteries has an activity between 5 and 15 times higher than in the umbilical cord vein and about 65% of the activity of the enzyme present in the maternal peripheral blood. The present results strongly suggest that in pregnancy the enzyme oestradiol-17 beta dehydrogenase is elaborated not only by the placenta but also by the foetus."}
{"id": "PMID:234999", "title": "Effects of hypothalamic extracts, neurotransmitters and synthetic hypothalamic releasing hormones on adenylyl cyclase activity in the lobes of the pituitary of the dogfish (Scyliorhinus canicula L.).", "content": "Neutralized acid extracts of the median eminence of the dogfish hypothalamus were found to cause a dose-related activation of adenylyl cyclase in all lobes of the dogfish pituitary. Equal concentrations of extracts of extrahypothalamic areas of the dogfish brain did not activate the enzyme. The putative neurotransmitters melatonin, serotonin, adrenaline, noradrenaline, dopamine and acetylcholine were without effect, as were the prostaglandins E1 and E2. The effects of synthetic mammalian hypothalamic hormones were also studied. Both thyrotrophin releasing hormone and gonadotrophin releasing hormone activated the ventral lobe enzyme, but had no effect on the adenylyl cyclase of the other three lobes. The tripeptide, Pro-Leu-Gly-NH2, a possible melanocyte-stimulating hormone release-inhibiting factor had no effect on the enzyme of the neurointermediate lobe. It is suggested that all four lobes of the dogfish pituitary may be under hypothalamic control and that this control is likely to be mediated by peptide hormones, as in mammals.", "contents": "Effects of hypothalamic extracts, neurotransmitters and synthetic hypothalamic releasing hormones on adenylyl cyclase activity in the lobes of the pituitary of the dogfish (Scyliorhinus canicula L.). Neutralized acid extracts of the median eminence of the dogfish hypothalamus were found to cause a dose-related activation of adenylyl cyclase in all lobes of the dogfish pituitary. Equal concentrations of extracts of extrahypothalamic areas of the dogfish brain did not activate the enzyme. The putative neurotransmitters melatonin, serotonin, adrenaline, noradrenaline, dopamine and acetylcholine were without effect, as were the prostaglandins E1 and E2. The effects of synthetic mammalian hypothalamic hormones were also studied. Both thyrotrophin releasing hormone and gonadotrophin releasing hormone activated the ventral lobe enzyme, but had no effect on the adenylyl cyclase of the other three lobes. The tripeptide, Pro-Leu-Gly-NH2, a possible melanocyte-stimulating hormone release-inhibiting factor had no effect on the enzyme of the neurointermediate lobe. It is suggested that all four lobes of the dogfish pituitary may be under hypothalamic control and that this control is likely to be mediated by peptide hormones, as in mammals."}
{"id": "PMID:235000", "title": "Binding of human chorionic gonadotrophin by rat testis: effect of sexual maturation, cryptorchidism and hypophysectomy.", "content": "The specific binding of 125I-labelled human chorionic gonadotrophin (HCG) by rat testicular homogenate as compared with isolated Leydig cells differs with respect to total binding capacity but not to the dissociation constant (Kd) as revealed by Scatchard analysis. The maximal binding capacity for [125I]HCG of crude testicular homogenate was 95 ng/g rat testis. Hypophysectomy causes a decline in binding capacity within the first three days but on the 20th and 30th day after hypophysectomy the relative binding capacity no longer differs from that of controls. Binding capacity is enhanced in cryptorchid testes relative to normal, and increases during sexual maturation to a peak shortly before puberty.", "contents": "Binding of human chorionic gonadotrophin by rat testis: effect of sexual maturation, cryptorchidism and hypophysectomy. The specific binding of 125I-labelled human chorionic gonadotrophin (HCG) by rat testicular homogenate as compared with isolated Leydig cells differs with respect to total binding capacity but not to the dissociation constant (Kd) as revealed by Scatchard analysis. The maximal binding capacity for [125I]HCG of crude testicular homogenate was 95 ng/g rat testis. Hypophysectomy causes a decline in binding capacity within the first three days but on the 20th and 30th day after hypophysectomy the relative binding capacity no longer differs from that of controls. Binding capacity is enhanced in cryptorchid testes relative to normal, and increases during sexual maturation to a peak shortly before puberty."}
{"id": "PMID:235002", "title": "Influence of dietary protein restriction on immune competence. I. Effect on the capacity of cells from various lymphoid organs to induce graft-vs.-host reactions.", "content": "The effect of dietary protein restriction in mice on the capacity of their lymphoid cells to induce graft-vs.-host responses (GVHR) was studied. Mice were fed diets containing 4% or 20% protein ad libitum. The GVHR capacity of cells from all lymphoid organs of deprived mice was increased on a cell-for-cell basis over that of their normally fed counterparts. The slope of the dose-response curves did not change for spleen and mesenteric lymph node cells although their reactivity was increased by fourfold, and 50% respectively. The slope of the curves for thymus and Peyer's patches was changed indicating fundamental changes in the reactive cellular populations of these organs. Changes in GVH reactivity of cell populations from deprived mice were not mediated by increased corticosteroid production as adrenalectomy did not reduce their GVH responses. An explanation for the results was sought in a general decrease in production of short-lived cells with a rapid turnover such as most B cells. Long-lived T cells appear to persist and retain their reactivity for quite long periods in the face of nutritional insults.", "contents": "Influence of dietary protein restriction on immune competence. I. Effect on the capacity of cells from various lymphoid organs to induce graft-vs.-host reactions. The effect of dietary protein restriction in mice on the capacity of their lymphoid cells to induce graft-vs.-host responses (GVHR) was studied. Mice were fed diets containing 4% or 20% protein ad libitum. The GVHR capacity of cells from all lymphoid organs of deprived mice was increased on a cell-for-cell basis over that of their normally fed counterparts. The slope of the dose-response curves did not change for spleen and mesenteric lymph node cells although their reactivity was increased by fourfold, and 50% respectively. The slope of the curves for thymus and Peyer's patches was changed indicating fundamental changes in the reactive cellular populations of these organs. Changes in GVH reactivity of cell populations from deprived mice were not mediated by increased corticosteroid production as adrenalectomy did not reduce their GVH responses. An explanation for the results was sought in a general decrease in production of short-lived cells with a rapid turnover such as most B cells. Long-lived T cells appear to persist and retain their reactivity for quite long periods in the face of nutritional insults."}
{"id": "PMID:235003", "title": "Early cellular events in a systemic graft-vs.-host reaction. I. The migration of responding and nonresponding donor lymphocytes.", "content": "A systemic graft-vs.-host (GVH) reaction was initiated by the intravenous injection of parental strain thoracic duct lymphocytes (TDL) into irradiated F1 hybrid recipients with in-dwelling thoracic duct cannulae. The migration of the donor lymphocytes was followed by labeling them in vitro with either [3H] or [14C]uridine and measuring radioactivity by scintillation counting of the spleen and lymph nodes of the recipients removed 24 h after injection and in TDL collected throughout this period. The localization of labeled cells was always compared to that of a reference population of nonreactive lymphocytes, e.g. F1 hybrid, labeled with the alternative isotope (Fig. 1). A consistent surplus of the reactive label was found in the spleen which was balanced by a deficit of the reactive label in TDL; lymph nodes gave intermediate values. The same distribution pattern was noted when the reference population was a specifically unresponsive population of the parental strain. This differential distribution depends on recognition of the recipient's Ag-B antigens because when normal lymphocytes were injected together with specifically unresponsive lymphocytes into a \"third party\" F1 hybrid (against which both populations were reactive) there was no surplus of the normal cells in the spleen and no deficit in the lymph. Moreover in an Ag-B identical strain combination there was no detectable difference in the distribution of reactive and nonreactive populations. The distribution of a labeled reaction population can be accounted for if a substantial minority of cells are immobilized in the spleen and lymph nodes as a consequence of antigen recognition (Fig. 3). When the donor cells in the spleen were assayed 24 h after injection there was paradoxically a slight reduction in their specific GVH activity, which is at least partly because they are under-represented in a single cell suspension. The size of the splenic surplus (23%) and the thoracic duct deficit (12%) suggested that the minority of nonimmune lymphocytes which recognize each Ag-B complex carry 12% of the radioactive label in the original population. It is argued that this provides a near estimate of the frequency of T lymphocytes which can recognize each Ag-B antigenic complex.", "contents": "Early cellular events in a systemic graft-vs.-host reaction. I. The migration of responding and nonresponding donor lymphocytes. A systemic graft-vs.-host (GVH) reaction was initiated by the intravenous injection of parental strain thoracic duct lymphocytes (TDL) into irradiated F1 hybrid recipients with in-dwelling thoracic duct cannulae. The migration of the donor lymphocytes was followed by labeling them in vitro with either [3H] or [14C]uridine and measuring radioactivity by scintillation counting of the spleen and lymph nodes of the recipients removed 24 h after injection and in TDL collected throughout this period. The localization of labeled cells was always compared to that of a reference population of nonreactive lymphocytes, e.g. F1 hybrid, labeled with the alternative isotope (Fig. 1). A consistent surplus of the reactive label was found in the spleen which was balanced by a deficit of the reactive label in TDL; lymph nodes gave intermediate values. The same distribution pattern was noted when the reference population was a specifically unresponsive population of the parental strain. This differential distribution depends on recognition of the recipient's Ag-B antigens because when normal lymphocytes were injected together with specifically unresponsive lymphocytes into a \"third party\" F1 hybrid (against which both populations were reactive) there was no surplus of the normal cells in the spleen and no deficit in the lymph. Moreover in an Ag-B identical strain combination there was no detectable difference in the distribution of reactive and nonreactive populations. The distribution of a labeled reaction population can be accounted for if a substantial minority of cells are immobilized in the spleen and lymph nodes as a consequence of antigen recognition (Fig. 3). When the donor cells in the spleen were assayed 24 h after injection there was paradoxically a slight reduction in their specific GVH activity, which is at least partly because they are under-represented in a single cell suspension. The size of the splenic surplus (23%) and the thoracic duct deficit (12%) suggested that the minority of nonimmune lymphocytes which recognize each Ag-B complex carry 12% of the radioactive label in the original population. It is argued that this provides a near estimate of the frequency of T lymphocytes which can recognize each Ag-B antigenic complex."}
{"id": "PMID:235004", "title": "Early cellular events in a systemic graft-vs.-host reaction. II. Autoradiographic estimates of the frequency of donor lymphocytes which respond to each Ag-B-determined antigenic complex.", "content": "A graft-vs.-host (GVH) reaction was initiated by the intravenous injection of parental strain (AO) lymphocytes into irradiated (AO times HO)F1 or (AO times DA)F1 hybrids. The proportion of donor T cells which had responded to the F1 hybrid antigens within 24 h was estimated by two methods. (a) Donor lymphocytes were labeled with [3H]uridine in vitro before injection. The proportion of labeled cells which had morphologically transformed in the recipient's spleen was 17-19%. In both series of experiments syngeneic transfers were performed in which case the proportion of transformed cells was 1-2.4%. A similar low proportion was found after parental to F1 transfer in a non-Ag-B strain combination. These figures were used to calculate the frequency of responding cells in the injected population given three additional pieces of information: (a) the extent of selection in the spleen which transformed the estimate to 4.5%-6.0% responders; (b) division of donor cells was shown to be negligible under the conditions of the experiment; and (c) the nonspecific recruitment of lymphocytes was shown to be negligible. A speculative model of antigen recognition by T cells which accounts for the high proportion of responders is outlined.", "contents": "Early cellular events in a systemic graft-vs.-host reaction. II. Autoradiographic estimates of the frequency of donor lymphocytes which respond to each Ag-B-determined antigenic complex. A graft-vs.-host (GVH) reaction was initiated by the intravenous injection of parental strain (AO) lymphocytes into irradiated (AO times HO)F1 or (AO times DA)F1 hybrids. The proportion of donor T cells which had responded to the F1 hybrid antigens within 24 h was estimated by two methods. (a) Donor lymphocytes were labeled with [3H]uridine in vitro before injection. The proportion of labeled cells which had morphologically transformed in the recipient's spleen was 17-19%. In both series of experiments syngeneic transfers were performed in which case the proportion of transformed cells was 1-2.4%. A similar low proportion was found after parental to F1 transfer in a non-Ag-B strain combination. These figures were used to calculate the frequency of responding cells in the injected population given three additional pieces of information: (a) the extent of selection in the spleen which transformed the estimate to 4.5%-6.0% responders; (b) division of donor cells was shown to be negligible under the conditions of the experiment; and (c) the nonspecific recruitment of lymphocytes was shown to be negligible. A speculative model of antigen recognition by T cells which accounts for the high proportion of responders is outlined."}
{"id": "PMID:235005", "title": "Psychiatric screening of civil service candidates with particular reference to police applicants.", "content": "This prelimary report has reviewed the activities of a Medical Review Board for a Civil Service Commission. The responsibility of the Board is to review conflicting data in cases where the hiring authority has attempted to exclude a candidate, particularly a police candidate, on the grounds that the applicant is mentally unfit to perform the duties of the position. This rule has been applied primarily to police applicants, secondarily to fireman applicants, and rarely to other. Psychiatrists who participate must be aware of the underlying conflicts within civil service systems, the possibility of manipulation, and the rigidity of the system which is designed to protect the greatest number. Civil service systems have limited discretion on personnel policies. Therefore, psychiatrists must be careful not to act as arbiters for social institutions without a sound and meticulous basis for their participation. For those psychiatrists who participate in the process, the urgent need to do so in accord with professional standards is stressed, recognizing that standards change and that the nature of participation will be scrutinized by many in society outside the profession.", "contents": "Psychiatric screening of civil service candidates with particular reference to police applicants. This prelimary report has reviewed the activities of a Medical Review Board for a Civil Service Commission. The responsibility of the Board is to review conflicting data in cases where the hiring authority has attempted to exclude a candidate, particularly a police candidate, on the grounds that the applicant is mentally unfit to perform the duties of the position. This rule has been applied primarily to police applicants, secondarily to fireman applicants, and rarely to other. Psychiatrists who participate must be aware of the underlying conflicts within civil service systems, the possibility of manipulation, and the rigidity of the system which is designed to protect the greatest number. Civil service systems have limited discretion on personnel policies. Therefore, psychiatrists must be careful not to act as arbiters for social institutions without a sound and meticulous basis for their participation. For those psychiatrists who participate in the process, the urgent need to do so in accord with professional standards is stressed, recognizing that standards change and that the nature of participation will be scrutinized by many in society outside the profession."}
{"id": "PMID:235006", "title": "Identification of flurazepam (Dalmane) and a primary metabolite in urine by thin-layer chromatography.", "content": "A relatively simple, routine method has been described for the qualitative identification of flurazepam and its primary metabolite 7-chloro-1-(2-hydroxyethyl)-5-(2-fluorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one in urine. We have described two extractions and several identification procedures by which flurazepam and its primary urinary metabolite can be identified by TLC.", "contents": "Identification of flurazepam (Dalmane) and a primary metabolite in urine by thin-layer chromatography. A relatively simple, routine method has been described for the qualitative identification of flurazepam and its primary metabolite 7-chloro-1-(2-hydroxyethyl)-5-(2-fluorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one in urine. We have described two extractions and several identification procedures by which flurazepam and its primary urinary metabolite can be identified by TLC."}
{"id": "PMID:235007", "title": "Squid retinochrome.", "content": "Retinochrome is a photosensitive pigment located primarily in the inner portions of the visual cells of cephalopods. Its absorption spectrum resembles that of rhodopsin, but its chromophore is all-trans retinal, which light isomerizes to 11-cis, the reverse of the situation in rhodopsin. The 11-cis photoproduct of retinochrome slowly reverts to retinochrome in the dark. The chromophoric site of retinochrome is more reactive than that of most visual pigments: (a) Hydroxylamine converts retinochrome in the dark to all-trans retinal oxime + retinochrome opsin. (by Sodium borohydride reduces it to N-retinyl opsin. (c) Lambda max of retinochrome shifts from 500 to 515 nm as the pH is raised from 6 to 10, with a loss of absorption above pH 8; meanwhile above this PH a second band appears at shorter wavelengths with lambda max 375 nm. These changes are reversible. (d) If retinochrome is incubated with all-trans 3-dehydroretinal (retinal2) in the dark, some 3-dehydroretinochrome (retinochrome2, lambda max about 515 nm) is formed. Conversely, when retinochrome2, made by adding all-trans retinal2 to bleached retinochrome or retinochrome opsin, is incubated in the dark with all-trans retinal some of it is converted to retinochrome. Retinal and 3-dehydroretinal therefore can replace each other as chromophores in the dark.", "contents": "Squid retinochrome. Retinochrome is a photosensitive pigment located primarily in the inner portions of the visual cells of cephalopods. Its absorption spectrum resembles that of rhodopsin, but its chromophore is all-trans retinal, which light isomerizes to 11-cis, the reverse of the situation in rhodopsin. The 11-cis photoproduct of retinochrome slowly reverts to retinochrome in the dark. The chromophoric site of retinochrome is more reactive than that of most visual pigments: (a) Hydroxylamine converts retinochrome in the dark to all-trans retinal oxime + retinochrome opsin. (by Sodium borohydride reduces it to N-retinyl opsin. (c) Lambda max of retinochrome shifts from 500 to 515 nm as the pH is raised from 6 to 10, with a loss of absorption above pH 8; meanwhile above this PH a second band appears at shorter wavelengths with lambda max 375 nm. These changes are reversible. (d) If retinochrome is incubated with all-trans 3-dehydroretinal (retinal2) in the dark, some 3-dehydroretinochrome (retinochrome2, lambda max about 515 nm) is formed. Conversely, when retinochrome2, made by adding all-trans retinal2 to bleached retinochrome or retinochrome opsin, is incubated in the dark with all-trans retinal some of it is converted to retinochrome. Retinal and 3-dehydroretinal therefore can replace each other as chromophores in the dark."}
{"id": "PMID:235008", "title": "Minor tranquilizers in the treatment of aggression.", "content": "Clinical trials designed to evaluate the efficacy of drugs in human aggression have been scarce until recent years. The potential antiaggressive action of minor tranquilizers in humans has received little attention in spite of the claimed \"taming effect\" in some animal studies. A recent report examining the literature regarding the effects of benzodiazepines on animal models of aggressive behavior has pointed out the lack of consistency in such findings. Similar observations have been noted in humans where reduction in aggressive manifestations is contrasted with an increase in hostility in a few studies, as well as with the appearance of \"paradoxical\" rage reactions. Some variables that could account for such discrepancies have been advanced. They include, among others, dosage, acute vs. chronic drug administration, and possible qualitive differences among this group of agents. Individual variations as to presenting clinical picture, initial levels of anxiety and hostility, and personality types have also been mentioned. Implications of some of these findings for future clinical research are discussed. At present, a study designed to test the efficacy of two benzodiazepines, at dosages higher than those usually recommended, is being carried out in a population of anxious, aggressive-prone individuals with poor impulse control. Thus far, and in agreement with our previous clinical experience, we have not seen \"paradoxical\" rage and such high dosages have been well tolerated.", "contents": "Minor tranquilizers in the treatment of aggression. Clinical trials designed to evaluate the efficacy of drugs in human aggression have been scarce until recent years. The potential antiaggressive action of minor tranquilizers in humans has received little attention in spite of the claimed \"taming effect\" in some animal studies. A recent report examining the literature regarding the effects of benzodiazepines on animal models of aggressive behavior has pointed out the lack of consistency in such findings. Similar observations have been noted in humans where reduction in aggressive manifestations is contrasted with an increase in hostility in a few studies, as well as with the appearance of \"paradoxical\" rage reactions. Some variables that could account for such discrepancies have been advanced. They include, among others, dosage, acute vs. chronic drug administration, and possible qualitive differences among this group of agents. Individual variations as to presenting clinical picture, initial levels of anxiety and hostility, and personality types have also been mentioned. Implications of some of these findings for future clinical research are discussed. At present, a study designed to test the efficacy of two benzodiazepines, at dosages higher than those usually recommended, is being carried out in a population of anxious, aggressive-prone individuals with poor impulse control. Thus far, and in agreement with our previous clinical experience, we have not seen \"paradoxical\" rage and such high dosages have been well tolerated."}
{"id": "PMID:235009", "title": "Conceptual issues in the use of drugs for the treatment of aggression in man.", "content": "Violence is a symptom of an underlying mental state such as a psychosis, a characterological problem, or brain dysfunction. Thus drugs used to treat aggression in man exert effects by their specific pharmacological actions (e.g., antipsychotic, anticonvulsant). Most literature to date has dealt with animals and human models of aggression and lacks conceptual clarity. Aggression differs from depression, a coherent clinical entity, in its etiological diversity and its paroxysmal or impulsive basis, and this may account for the relationship seen in literature linking violence to epilepsy; yet literature on anticonvulsants is equivocal with regard to beneficial effects on aggression. Lithium has been shown to have positive effects, although its mode of action is unclear. A variety of antipsychotic agents and minor tranquilizers have been mentioned. Central nervous system stimulants have been found useful to treat hyperkinetic syndromes in both children and adults where aggression is a symptom. Hormonal agents are discussed. Drug treatment of aggression should not obscure the need for verbal therapies, and social and environmental factors should always be regarded.", "contents": "Conceptual issues in the use of drugs for the treatment of aggression in man. Violence is a symptom of an underlying mental state such as a psychosis, a characterological problem, or brain dysfunction. Thus drugs used to treat aggression in man exert effects by their specific pharmacological actions (e.g., antipsychotic, anticonvulsant). Most literature to date has dealt with animals and human models of aggression and lacks conceptual clarity. Aggression differs from depression, a coherent clinical entity, in its etiological diversity and its paroxysmal or impulsive basis, and this may account for the relationship seen in literature linking violence to epilepsy; yet literature on anticonvulsants is equivocal with regard to beneficial effects on aggression. Lithium has been shown to have positive effects, although its mode of action is unclear. A variety of antipsychotic agents and minor tranquilizers have been mentioned. Central nervous system stimulants have been found useful to treat hyperkinetic syndromes in both children and adults where aggression is a symptom. Hormonal agents are discussed. Drug treatment of aggression should not obscure the need for verbal therapies, and social and environmental factors should always be regarded."}
{"id": "PMID:235010", "title": "Treatment of human aggression with major tranquilizers, antidepressants, and newer psychotropic drugs.", "content": "Most of the drugs used in the treatment of aggressive syndromes have originally been developed for other clinical applications. Despite significant differences in the pathogenesis of various aggressive disorders, the frequently used \"antiaggression\" drugs are the major tranquilizers (neuroleptics). If the aggresstion is associated with psychosis, chlorpromazine or haloperidol are the drugs of choice. Aggressive disorders within the acute and chronic brain syndromes are best treated with pericyazine, thioridazine, and thiothixene. In aggressive symptoms of mentally retarded patients, particularly with epileptic syndromes, a new benzazepine (SCH12,679)was found to be very effective. Aggression associated with alcoholism or narcotic addiction showed best response to chlorpormazine and haloperidol. As a general rule, in aggressive patients with clinically known epilepsy, or with abnormal electroencephalographic findings, the major tranquilizers with potent sedative properties should be given with great caution.", "contents": "Treatment of human aggression with major tranquilizers, antidepressants, and newer psychotropic drugs. Most of the drugs used in the treatment of aggressive syndromes have originally been developed for other clinical applications. Despite significant differences in the pathogenesis of various aggressive disorders, the frequently used \"antiaggression\" drugs are the major tranquilizers (neuroleptics). If the aggresstion is associated with psychosis, chlorpromazine or haloperidol are the drugs of choice. Aggressive disorders within the acute and chronic brain syndromes are best treated with pericyazine, thioridazine, and thiothixene. In aggressive symptoms of mentally retarded patients, particularly with epileptic syndromes, a new benzazepine (SCH12,679)was found to be very effective. Aggression associated with alcoholism or narcotic addiction showed best response to chlorpormazine and haloperidol. As a general rule, in aggressive patients with clinically known epilepsy, or with abnormal electroencephalographic findings, the major tranquilizers with potent sedative properties should be given with great caution."}
{"id": "PMID:235011", "title": "Abnormal intrafusal muscle fibres in myotonic dystrophy: a study using serial sections.", "content": "Studies of the extent and complexity of intrafusal muscle fibre splitting in myotonic dystrophy have been carried out in three spindles obtained at muscle biopsy, and in nine spindles found in the lumbrical muscle of a case that came to necropsy. It is suggested that splitting, due to mechanical stresses, leads to a regenerative response in the separated fragments.", "contents": "Abnormal intrafusal muscle fibres in myotonic dystrophy: a study using serial sections. Studies of the extent and complexity of intrafusal muscle fibre splitting in myotonic dystrophy have been carried out in three spindles obtained at muscle biopsy, and in nine spindles found in the lumbrical muscle of a case that came to necropsy. It is suggested that splitting, due to mechanical stresses, leads to a regenerative response in the separated fragments."}
{"id": "PMID:235012", "title": "Lipid storage myopathy with normal carnitine levels.", "content": "A 28-year-old female, who showed a floppy baby syndrome during early infancy, had a non-progressive proximal muscle weakness with easy fatiguability since childhood. Two muscle specimens biopsied at the age of 28 years revealed myriads of 1-3-mum wide abnormal spaces containing neutral fat in type I and type II fibers.  Both biopsies demonstrated a type I fiber preponderance.  Electron microscopy demonstrated lipid excess and normal mitochondria by simple inspection. The mitochondrial area and sarcotubular membrane profile concentration in morphometry of longitudinal sections were also normal.  Cross-sections, however, revealed a slight decrease of the individual mitochondrial size and of the sarcotubular membrane profile concentration . Serum and muscle carnitine levels and the muscle carnitine palmityltransferase level were all within normal range.  Besides carnitine deficiency other biochemical defects can occur in lipid storage myopathy, which represents a syndrome rather than a unique disease entity.", "contents": "Lipid storage myopathy with normal carnitine levels. A 28-year-old female, who showed a floppy baby syndrome during early infancy, had a non-progressive proximal muscle weakness with easy fatiguability since childhood. Two muscle specimens biopsied at the age of 28 years revealed myriads of 1-3-mum wide abnormal spaces containing neutral fat in type I and type II fibers.  Both biopsies demonstrated a type I fiber preponderance.  Electron microscopy demonstrated lipid excess and normal mitochondria by simple inspection. The mitochondrial area and sarcotubular membrane profile concentration in morphometry of longitudinal sections were also normal.  Cross-sections, however, revealed a slight decrease of the individual mitochondrial size and of the sarcotubular membrane profile concentration . Serum and muscle carnitine levels and the muscle carnitine palmityltransferase level were all within normal range.  Besides carnitine deficiency other biochemical defects can occur in lipid storage myopathy, which represents a syndrome rather than a unique disease entity."}
{"id": "PMID:235013", "title": "Tardive dyskinesia treated with pimozide.", "content": "We have investigated the action of pimozide in tardive dyskinesia induced by prolonged administration of phenothiazines. Improvement was recorded in a double blind study of 18 patients treated with maximum tolerated dosage (mean 18.8 mg/day) for 6 weeks. There was no deterioration in the therapeutic action of pimozide over this time. Parkinsonism and sedation were the main adverse effects. They were corrected by reduction of the dose of pimozide, but often recurred so that further adjustments of dosage were necessary. Our findings support the view that tardive dyskinesia is produced by a disturbance in the balance of central transmitters such that dopaminergic transmission is increased.", "contents": "Tardive dyskinesia treated with pimozide. We have investigated the action of pimozide in tardive dyskinesia induced by prolonged administration of phenothiazines. Improvement was recorded in a double blind study of 18 patients treated with maximum tolerated dosage (mean 18.8 mg/day) for 6 weeks. There was no deterioration in the therapeutic action of pimozide over this time. Parkinsonism and sedation were the main adverse effects. They were corrected by reduction of the dose of pimozide, but often recurred so that further adjustments of dosage were necessary. Our findings support the view that tardive dyskinesia is produced by a disturbance in the balance of central transmitters such that dopaminergic transmission is increased."}
{"id": "PMID:235014", "title": "A follow-up study of surgically treated cryptorchid patients.", "content": "A group of 112 adult patients were traced who had had childhood orchiopexies at an average age of 9 yr at two childrens' hospitals. Sixty-seven per cent of all married patients had sired children although only 44% of the married bilateral cryptorchid patients had done so. The percentage paternity of the unilaterally cryptorchid patients was normal when compared with the general population. There appeared to be no difference in the eventual results of the two types of orchiopexy performed on this series of patients.", "contents": "A follow-up study of surgically treated cryptorchid patients. A group of 112 adult patients were traced who had had childhood orchiopexies at an average age of 9 yr at two childrens' hospitals. Sixty-seven per cent of all married patients had sired children although only 44% of the married bilateral cryptorchid patients had done so. The percentage paternity of the unilaterally cryptorchid patients was normal when compared with the general population. There appeared to be no difference in the eventual results of the two types of orchiopexy performed on this series of patients."}
{"id": "PMID:235015", "title": "Surgical correction of cryptorchism at 2 years: electron microscopic and morphometric investigations.", "content": "Electron microscopic and morphometric investigations on undescended testicles show a decreased volume density of the spermatogonia up to the age of 5 (approximately 60%, p smaller than 0.005), corresponding to investigations by light microscopy. There are no ultrastructural differences in the seminiferous tubules between normal and undescended testicles up to the age of 1 yr. There are ultrastructural changes of Leydig cells within the first year of life. Based on these investigations, we conclude that the optimal time for surgical intervention in case of undescended testes is in the second year.", "contents": "Surgical correction of cryptorchism at 2 years: electron microscopic and morphometric investigations. Electron microscopic and morphometric investigations on undescended testicles show a decreased volume density of the spermatogonia up to the age of 5 (approximately 60%, p smaller than 0.005), corresponding to investigations by light microscopy. There are no ultrastructural differences in the seminiferous tubules between normal and undescended testicles up to the age of 1 yr. There are ultrastructural changes of Leydig cells within the first year of life. Based on these investigations, we conclude that the optimal time for surgical intervention in case of undescended testes is in the second year."}
{"id": "PMID:235016", "title": "Plasma gonadotropins and androgens in surgically treated cryptorchid patients.", "content": "Plasma LH, FSH, and total 17betaOH androgen levels were measured in a group of 40 adult patients who underwent orchiopexy for either unilateral or bilateral cryptorchism during childhood. Gonadotropin abnormalities were found in 15 of 40 patients and thereby appeared to be a much more sensitive indicator of testicular malfunction than the androgens which were abnormal in only four patients. In the postpubertal phase, the estimation of gonadotropins and androgens appeared valuable, first, as an additional help in the prognosis of fertility, where combined raised levels of LH and FSH were found to indicate a poor prognosis; second, to detect in infertile patients gonadotropin deficiency which, if previously missed, can still be expected to respond to gonadotropin therapy; third, for the detection of the subclinically hypogonad group who may require follow-up, and finally for the detection of the low-androgen group who may require some form of hormonal therapy. As several patients in this study were found to have low gonadotropins, it is postulated that low levels of gonadotropin may play a role in the production of cryptorchism. The finding of high gonadotropin levels in another group may indicate a feedback mechanism sensitive to a damaged testis, but alternatively it is possible that there might be a primary resistance to the action of gonadotropins and it is postulated that such a resistance may be an additional factor of the causation of cryptorchism in some cases.", "contents": "Plasma gonadotropins and androgens in surgically treated cryptorchid patients. Plasma LH, FSH, and total 17betaOH androgen levels were measured in a group of 40 adult patients who underwent orchiopexy for either unilateral or bilateral cryptorchism during childhood. Gonadotropin abnormalities were found in 15 of 40 patients and thereby appeared to be a much more sensitive indicator of testicular malfunction than the androgens which were abnormal in only four patients. In the postpubertal phase, the estimation of gonadotropins and androgens appeared valuable, first, as an additional help in the prognosis of fertility, where combined raised levels of LH and FSH were found to indicate a poor prognosis; second, to detect in infertile patients gonadotropin deficiency which, if previously missed, can still be expected to respond to gonadotropin therapy; third, for the detection of the subclinically hypogonad group who may require follow-up, and finally for the detection of the low-androgen group who may require some form of hormonal therapy. As several patients in this study were found to have low gonadotropins, it is postulated that low levels of gonadotropin may play a role in the production of cryptorchism. The finding of high gonadotropin levels in another group may indicate a feedback mechanism sensitive to a damaged testis, but alternatively it is possible that there might be a primary resistance to the action of gonadotropins and it is postulated that such a resistance may be an additional factor of the causation of cryptorchism in some cases."}
{"id": "PMID:235017", "title": "The effect of cigarette smoking on anaerobiosis in the oral cavity.", "content": "Nineteen young adult male smokers were compared to 19 adult male nonsmokers to determine if cigarette smoking resulted in any changes to anaerobic bacteria in dental plaque, to intraoral oxidation-reduction potential (Eh) levels, or to intraoral pH. There was no statistical difference between smokers and nonsmokers in the proportion of anaerobic bacteria found in dental plaque. There were no significant differences between smokers and nonsmokers with respect to the resting Eh in the floor of the mouth nor in the Eh in the region of buccal surface of the upper molars. The smoking of one cigarette resulted in a dramatic fall in Eh in both intraoral regions and this occurred in all subjects, both smokers and nonsmokers. The magnitude of this fall in Eh was similar in both groups. There were also uniform increases in pH, but these pH changes were much smaller in magnitude.", "contents": "The effect of cigarette smoking on anaerobiosis in the oral cavity. Nineteen young adult male smokers were compared to 19 adult male nonsmokers to determine if cigarette smoking resulted in any changes to anaerobic bacteria in dental plaque, to intraoral oxidation-reduction potential (Eh) levels, or to intraoral pH. There was no statistical difference between smokers and nonsmokers in the proportion of anaerobic bacteria found in dental plaque. There were no significant differences between smokers and nonsmokers with respect to the resting Eh in the floor of the mouth nor in the Eh in the region of buccal surface of the upper molars. The smoking of one cigarette resulted in a dramatic fall in Eh in both intraoral regions and this occurred in all subjects, both smokers and nonsmokers. The magnitude of this fall in Eh was similar in both groups. There were also uniform increases in pH, but these pH changes were much smaller in magnitude."}
{"id": "PMID:235018", "title": "Role of the cell membrane in the uptake of 3H-actinomycin D by mammalian cells in vitro.", "content": "The characteristics of the uptake of 3H-Actinomycin D (3H-AMD) by mammalian cells was studied in vitro.  Chang liver (CH) cells accululated 3H-AMD over 100 times above extracellular levels.  CH cells accumulated and released 3H-AMD at a slow rate.  Treatment of cells with ethanol-acetone or Tween 80 significantly increased the rates of drug uptake and release by cells, indicating that the cell membrane effectively slows down passage of 3H-AMD in and out of cells.  Cellular 3H-AMD uptake is temperature dependent and not energy dependent.  The rates of 3H-AMD uptake after short and prolonged incubation suggest that AMD entry into cells consists of two phases, an initial phase of rate-limiting diffusion process followed by a second phase of binding to deoxyribonucleic acid.  Although lymphocytes take up less 3H-AMD than CH cells, the differential inhibitory effect of AMD on nucleic acid synthesis in the two cell types is small.  The time required for cells to be fully saturated with 3H-AMD varies with the cell type and is based on permeability differences of the cell membrane for 3H-AMD.  The time required for lymphocytes and CH cells to be fully saturated with 3H-AMD is reflected in the differential effect of the drug on nucleic acid synthesis.  The physiological basis of AMD resistance can be explained on the basis of impaired diffusion of the drug into cells.", "contents": "Role of the cell membrane in the uptake of 3H-actinomycin D by mammalian cells in vitro. The characteristics of the uptake of 3H-Actinomycin D (3H-AMD) by mammalian cells was studied in vitro.  Chang liver (CH) cells accululated 3H-AMD over 100 times above extracellular levels.  CH cells accumulated and released 3H-AMD at a slow rate.  Treatment of cells with ethanol-acetone or Tween 80 significantly increased the rates of drug uptake and release by cells, indicating that the cell membrane effectively slows down passage of 3H-AMD in and out of cells.  Cellular 3H-AMD uptake is temperature dependent and not energy dependent.  The rates of 3H-AMD uptake after short and prolonged incubation suggest that AMD entry into cells consists of two phases, an initial phase of rate-limiting diffusion process followed by a second phase of binding to deoxyribonucleic acid.  Although lymphocytes take up less 3H-AMD than CH cells, the differential inhibitory effect of AMD on nucleic acid synthesis in the two cell types is small.  The time required for cells to be fully saturated with 3H-AMD varies with the cell type and is based on permeability differences of the cell membrane for 3H-AMD.  The time required for lymphocytes and CH cells to be fully saturated with 3H-AMD is reflected in the differential effect of the drug on nucleic acid synthesis.  The physiological basis of AMD resistance can be explained on the basis of impaired diffusion of the drug into cells."}
{"id": "PMID:235019", "title": "Stereospecific blockage of the alpha adrenergic receptor by substituted 1-aminotetralines.", "content": "Certain members of a series of 1-aminotetraline derivatives reversed the epinephrine pressor response in dogs; this effect occurred with the R- but not the S-isomers.  Studies with rabbit aortic strips indicated competitive blockade of the alpha adrenergic receptor by the active agents.  Receptor protection experiments supported the interpretation that this disruption of receptor function was due to occupancy blockade.  This led to a hypothesis defining the steric properties of the alpha receptor and the active conformation of epinephrine at this receptor.  However, two hydroxy substituted 1-aminotetralines ans two trihydroxytetrahydrosioquinoline derivatives, which were investigated to support this hypothesis, failed to show the predicted alpha adrenergic agonist activity.  It is concluded that the interaction of certain 1-aminotetralines with a stereospecific binding site at the alpha receptor mimics occupancy blockade.  However, this binding site is probably not entirely identical with the epinephrine binding site at the alpha receptor.  Furthermore, the cyclic tetrahydroisoquinoline derivatives do not represent the active conformation of epinephrine at the receptor.", "contents": "Stereospecific blockage of the alpha adrenergic receptor by substituted 1-aminotetralines. Certain members of a series of 1-aminotetraline derivatives reversed the epinephrine pressor response in dogs; this effect occurred with the R- but not the S-isomers.  Studies with rabbit aortic strips indicated competitive blockade of the alpha adrenergic receptor by the active agents.  Receptor protection experiments supported the interpretation that this disruption of receptor function was due to occupancy blockade.  This led to a hypothesis defining the steric properties of the alpha receptor and the active conformation of epinephrine at this receptor.  However, two hydroxy substituted 1-aminotetralines ans two trihydroxytetrahydrosioquinoline derivatives, which were investigated to support this hypothesis, failed to show the predicted alpha adrenergic agonist activity.  It is concluded that the interaction of certain 1-aminotetralines with a stereospecific binding site at the alpha receptor mimics occupancy blockade.  However, this binding site is probably not entirely identical with the epinephrine binding site at the alpha receptor.  Furthermore, the cyclic tetrahydroisoquinoline derivatives do not represent the active conformation of epinephrine at the receptor."}
{"id": "PMID:235020", "title": "An analysis of the sympathomimetic activity of 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (TIQ).", "content": "The pithed rat preparation has been used to study the sympathomimetic activity of 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (TIQ).  In this preparation, an increase in blood pressure is indicative of alpha stimulation, and an increase in heart rate is indicative of beta stimulation.  Using this preparation, we have found that TIQ is approximately 3 orders of magnitude less potent than norepinephrine in evoking changes in blood pressure and heart rate.  The activity of TIQ has also been studied in pithed animals which had been previously sympathectomized with 6-hydroxydopamine.  Sympathectomy produced a marked reduction in cardiac norepinephrine, and it nearly abolished vascular responses to injected tyramine.  Following sympathectomy, pithed animals were supersensitive to norepinephrine and subsensitive to TIQ. Similar results were obtained on pithed animals that had been pretreated with cocaine.  It is concluded that TIQ is a weak sympathomimetic agent possessing both directly and indirectly acting properties.  The data are discussed in terms of a proposal that TIQ may be a false adrenergic transmitter.", "contents": "An analysis of the sympathomimetic activity of 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (TIQ). The pithed rat preparation has been used to study the sympathomimetic activity of 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (TIQ).  In this preparation, an increase in blood pressure is indicative of alpha stimulation, and an increase in heart rate is indicative of beta stimulation.  Using this preparation, we have found that TIQ is approximately 3 orders of magnitude less potent than norepinephrine in evoking changes in blood pressure and heart rate.  The activity of TIQ has also been studied in pithed animals which had been previously sympathectomized with 6-hydroxydopamine.  Sympathectomy produced a marked reduction in cardiac norepinephrine, and it nearly abolished vascular responses to injected tyramine.  Following sympathectomy, pithed animals were supersensitive to norepinephrine and subsensitive to TIQ. Similar results were obtained on pithed animals that had been pretreated with cocaine.  It is concluded that TIQ is a weak sympathomimetic agent possessing both directly and indirectly acting properties.  The data are discussed in terms of a proposal that TIQ may be a false adrenergic transmitter."}
{"id": "PMID:235021", "title": "Inhibition of histidine, decarboxylation in vivo by 2-hydroxy-5-carbomethoxybenzyloxyamine, a new, potent inhibitor of histidine decarboxylase.", "content": "Measurements of the rate of expiration of 14CO2 were carried out after the injection into rats of 14C-histidine labeled in the carboxyl group (C-His) or in the imidazole ring (R-His).  Intraperitoneal administration of 2-hydroxy-5-carbomethoxybenzyloxyamine, a new potent inhibitor of histidine decarboxylase, reduced the rate of 14CO2 production from C-His and R-His in a dose-dependent manner.  The metabolism of C-His was more affected than that of R-His.  The inhibitor had no effect on the production of 14CO2 from 14C-urocanic acid, 14C-dopa or 14C-glutamic acid.  Rats given 2-hydroxy-5-carbomethoxybenzyloxyamine (100 mg/kg) by the intraperitoneal route had diminished histidine decarboxylase activity of stomach (96 percent decrease), but did not have any change in the activities of histidase, urocanase or histidine-pyruvate aminotransferase of liver.  After the administration of histidine (500 mg/kg), the level of this amino acid in serum remained elevated somewhat longer in inhibitor-treated animals than in the controls.  The temporary rise in serum histidine relative to controls that were also histidine-loaded is considered to reflect the decreased rate of uptake of histidine into the tissues, and also a decreased rate of decarboxylation of histidine in certain organs.  After the administration of 2-hydroxy-5-carbomethoxybenzyloxyamine, the decreased rate of 14CO2 production from injected R-His and the delayed disappearance of histidine from the serum after a histidine load were considered to reflect mainly the decreased rate of histidine uptake into the tissues.  The decreased rate of formation of 14CO obtained with C-His appeared to result from inhibition of both uptake and decarboxylation of histidine.", "contents": "Inhibition of histidine, decarboxylation in vivo by 2-hydroxy-5-carbomethoxybenzyloxyamine, a new, potent inhibitor of histidine decarboxylase. Measurements of the rate of expiration of 14CO2 were carried out after the injection into rats of 14C-histidine labeled in the carboxyl group (C-His) or in the imidazole ring (R-His).  Intraperitoneal administration of 2-hydroxy-5-carbomethoxybenzyloxyamine, a new potent inhibitor of histidine decarboxylase, reduced the rate of 14CO2 production from C-His and R-His in a dose-dependent manner.  The metabolism of C-His was more affected than that of R-His.  The inhibitor had no effect on the production of 14CO2 from 14C-urocanic acid, 14C-dopa or 14C-glutamic acid.  Rats given 2-hydroxy-5-carbomethoxybenzyloxyamine (100 mg/kg) by the intraperitoneal route had diminished histidine decarboxylase activity of stomach (96 percent decrease), but did not have any change in the activities of histidase, urocanase or histidine-pyruvate aminotransferase of liver.  After the administration of histidine (500 mg/kg), the level of this amino acid in serum remained elevated somewhat longer in inhibitor-treated animals than in the controls.  The temporary rise in serum histidine relative to controls that were also histidine-loaded is considered to reflect the decreased rate of uptake of histidine into the tissues, and also a decreased rate of decarboxylation of histidine in certain organs.  After the administration of 2-hydroxy-5-carbomethoxybenzyloxyamine, the decreased rate of 14CO2 production from injected R-His and the delayed disappearance of histidine from the serum after a histidine load were considered to reflect mainly the decreased rate of histidine uptake into the tissues.  The decreased rate of formation of 14CO obtained with C-His appeared to result from inhibition of both uptake and decarboxylation of histidine."}
{"id": "PMID:235022", "title": "Growth of Nosema algerae in pig kidney cell cultures.", "content": "Nosema algerae, a microsporidan parasite of mosquitoes, can infect pig kidney cell cultures.  Sores germinated in the culture medium, infected the cells within 30 min of germination, multiplied, and produced spores.  The early developmental stages in the N. algerae life cycle are discribed.", "contents": "Growth of Nosema algerae in pig kidney cell cultures. Nosema algerae, a microsporidan parasite of mosquitoes, can infect pig kidney cell cultures.  Sores germinated in the culture medium, infected the cells within 30 min of germination, multiplied, and produced spores.  The early developmental stages in the N. algerae life cycle are discribed."}
{"id": "PMID:235023", "title": "Nitrofuran-reducing enzymes of Euglena.", "content": "Euglena gracilis strain Z, green, dark-brown, and \"bleached\" with N-methyl-N-nitro-N-nitrosoguanidine, was found to contain 2 soluble enzymes which reduce nitrofurans.  A small amount of activity was demonstrated also in a particulate fraction of sonic extracts, but none in isolated chloroplasts.  The reduction of 5 nitrofurans, having widely differing bleaching activities, by each of the 2 enzymes was examined.", "contents": "Nitrofuran-reducing enzymes of Euglena. Euglena gracilis strain Z, green, dark-brown, and \"bleached\" with N-methyl-N-nitro-N-nitrosoguanidine, was found to contain 2 soluble enzymes which reduce nitrofurans.  A small amount of activity was demonstrated also in a particulate fraction of sonic extracts, but none in isolated chloroplasts.  The reduction of 5 nitrofurans, having widely differing bleaching activities, by each of the 2 enzymes was examined."}
{"id": "PMID:235025", "title": "Effect of initial freezing temperature, addition of glycerol and dilution on the survival and fertilizing ability of deep-frozen ram semen.", "content": "The influence oftemperature, addition of glycerol, initial freezing temperature, method of dilution, level of glycerol in the diluted semen, equilibration time and type of diluent on the survival and fertilizing capacity of deep-frozen according to the best conditions was compared with that of \"fresh\" semen. The addition of glycerol at plus30 degrees C resulted in a highly significant decrease in the mean proportion of motile spermatozoa immediately after thawing compared with the effect of addition at plus 4 degrees C. The immersion of the straws at minus55 degrees C significantly reduced the revival of the spermatozoa compared with initial freezing at lower temperatures. The exposure time to glycerol had no significant effect on the survival of spermatozoa after thawing and incubation, but fertility was significantly higher with 4% than with 2% glycerol. The I. N. R. A. diluent provided better sperm survival and a significantly higher conception rate than did lactose-egg yolk extender. The semen frozen according to the best conditions (about 50% of the samples) had a fertilizing ability similar to that of \"fresh\" semen when the proportion of motile spermatozoa before, and after 1 or 3 hr of incubation was equal to or above 45, 40 and 30% respectively.", "contents": "Effect of initial freezing temperature, addition of glycerol and dilution on the survival and fertilizing ability of deep-frozen ram semen. The influence oftemperature, addition of glycerol, initial freezing temperature, method of dilution, level of glycerol in the diluted semen, equilibration time and type of diluent on the survival and fertilizing capacity of deep-frozen according to the best conditions was compared with that of \"fresh\" semen. The addition of glycerol at plus30 degrees C resulted in a highly significant decrease in the mean proportion of motile spermatozoa immediately after thawing compared with the effect of addition at plus 4 degrees C. The immersion of the straws at minus55 degrees C significantly reduced the revival of the spermatozoa compared with initial freezing at lower temperatures. The exposure time to glycerol had no significant effect on the survival of spermatozoa after thawing and incubation, but fertility was significantly higher with 4% than with 2% glycerol. The I. N. R. A. diluent provided better sperm survival and a significantly higher conception rate than did lactose-egg yolk extender. The semen frozen according to the best conditions (about 50% of the samples) had a fertilizing ability similar to that of \"fresh\" semen when the proportion of motile spermatozoa before, and after 1 or 3 hr of incubation was equal to or above 45, 40 and 30% respectively."}
{"id": "PMID:235026", "title": "Maternal immunization to paternal antigens in multiparous mice.", "content": "Mice of the CBA strain which had given birth to five litters sired by males of a different H-2 type (C57BL/10) showed evidence of immunization to paternal antigens, in that the numbers of lymphocytes forming alloclusters with paternal erythrocytes were significantly elevated. On the other hand, the graft-versus-host responsiveness of maternal splenic lymphocytes to paternal antigens remained virtually unchanged, showing only a slight increase at Day 8 of the assay.", "contents": "Maternal immunization to paternal antigens in multiparous mice. Mice of the CBA strain which had given birth to five litters sired by males of a different H-2 type (C57BL/10) showed evidence of immunization to paternal antigens, in that the numbers of lymphocytes forming alloclusters with paternal erythrocytes were significantly elevated. On the other hand, the graft-versus-host responsiveness of maternal splenic lymphocytes to paternal antigens remained virtually unchanged, showing only a slight increase at Day 8 of the assay."}
{"id": "PMID:235027", "title": "Brain monoamine levels in the cow during oestrus and metoestrus.", "content": "Norepinephrine, dopamine, and serotonin concentrations in the hypothalamus and stalk-median eminence were estimated in nine Hereford heifers at the onset of oestrus or 48 hr later. Significant differences in levels of monoamines at these stages of the oestrous cycle were not evident. Norepinephrine levels were similar in the hypothalamus and the stalk-median eminence, but dopamine and serotonin concentrations were significantly higher in the stalk-median eminence.", "contents": "Brain monoamine levels in the cow during oestrus and metoestrus. Norepinephrine, dopamine, and serotonin concentrations in the hypothalamus and stalk-median eminence were estimated in nine Hereford heifers at the onset of oestrus or 48 hr later. Significant differences in levels of monoamines at these stages of the oestrous cycle were not evident. Norepinephrine levels were similar in the hypothalamus and the stalk-median eminence, but dopamine and serotonin concentrations were significantly higher in the stalk-median eminence."}
{"id": "PMID:235029", "title": "Treatment of circulatory shock. Use of sympathomimetic and related vasoactive agents.", "content": "Reduction of effective blood flow represents the primary disturbance accounting for circulatory shock. Four categories of circulatory shock are identified: cardiogenic, hypovolemic, distributive, and obstructive. The pharmacology and clinical implications for treatment of shock with vasoactive drugs are reviewed in this context. Except for epinephrine, when it is used for treatment of anaphylactic shock, there is no specific indication for the routine use of alpha- or beta-adrenergic receptor agonists. These agents may increase blood pressure or cardiac output, but nutritive flow is not necessarily improved. Comparable limitations are observed with alpha-adrenergic receptor blocking agents. However, selective effects on the myocardium and on the resistance, exchange, and capacitance vessels may be advantageous as an interim and complementary measure. Since vasoactive drugs frequently intensify the fundamental defect accounting for perfusion failure, their selective rather than routine employment is mandatory.", "contents": "Treatment of circulatory shock. Use of sympathomimetic and related vasoactive agents. Reduction of effective blood flow represents the primary disturbance accounting for circulatory shock. Four categories of circulatory shock are identified: cardiogenic, hypovolemic, distributive, and obstructive. The pharmacology and clinical implications for treatment of shock with vasoactive drugs are reviewed in this context. Except for epinephrine, when it is used for treatment of anaphylactic shock, there is no specific indication for the routine use of alpha- or beta-adrenergic receptor agonists. These agents may increase blood pressure or cardiac output, but nutritive flow is not necessarily improved. Comparable limitations are observed with alpha-adrenergic receptor blocking agents. However, selective effects on the myocardium and on the resistance, exchange, and capacitance vessels may be advantageous as an interim and complementary measure. Since vasoactive drugs frequently intensify the fundamental defect accounting for perfusion failure, their selective rather than routine employment is mandatory."}
{"id": "PMID:235030", "title": "Diplococcus pneumoniae. Cellulitis in drug addicts.", "content": "Cellulitis caused by Diplococcus pneumoniae was diagnosed in two heroin users. To our knowledge, this medical emergency, clinically indistinguishable from deep fasciitis of pyomyositis, has not previously been reported as having been caused by the agent identified in these two patients.", "contents": "Diplococcus pneumoniae. Cellulitis in drug addicts. Cellulitis caused by Diplococcus pneumoniae was diagnosed in two heroin users. To our knowledge, this medical emergency, clinically indistinguishable from deep fasciitis of pyomyositis, has not previously been reported as having been caused by the agent identified in these two patients."}
{"id": "PMID:235035", "title": "[Comparative evaluation of new drugs used in the treatment of cardiac arrhythmia].", "content": "The paper summarizes the experience gained in treating 830 patients with various cardiac rhythm disorders by employing new antirhythmic agents (propranolol, practolol, pindolol, alprenolol, oxyprenolol, benzoral, verapamil, lidocaine, imaline, sparteine, pulsonorma, disopyramide and quinidine durules). Comparative data on the efficacy of these agents are presented and indications and counterindications for their use are discussed.", "contents": "[Comparative evaluation of new drugs used in the treatment of cardiac arrhythmia]. The paper summarizes the experience gained in treating 830 patients with various cardiac rhythm disorders by employing new antirhythmic agents (propranolol, practolol, pindolol, alprenolol, oxyprenolol, benzoral, verapamil, lidocaine, imaline, sparteine, pulsonorma, disopyramide and quinidine durules). Comparative data on the efficacy of these agents are presented and indications and counterindications for their use are discussed."}
{"id": "PMID:235037", "title": "[Electroimpulse therapy of auricular fibrillation].", "content": "Data derived from clinical, electro- and polycardiographic observations of 68 patients subjected to electric stimulation therapy are presented. The evaluation of late results of the treatment showed that clinical factors such as the patients' age, the nature of the affection, the degree of cardiac insufficiency, the standing of auricular fibrillation are not decisive in determining indications and contraindication for electric stimulation therapy. A considerable worsening of the cardiac dynamics with developing fibrillation arrhythmia, especially in patients suffering from cardiosclerosis, and a distinct improvement of the polycardiographic indices after defibrillation point to the need of attempting, whenever this is possible, to bar the auricular fibrillation. A pretreatment with potassium preparations and lengthy maintenance therapy with quinidine or quinidine-like agents is recommended. An analysis of the ECG findings after the electric stimulation therapy (heart rate, and its regularity, the state of the intraatrial and atrioventricular conduction) enable it to foresee the retention time of the re-established rhythm.", "contents": "[Electroimpulse therapy of auricular fibrillation]. Data derived from clinical, electro- and polycardiographic observations of 68 patients subjected to electric stimulation therapy are presented. The evaluation of late results of the treatment showed that clinical factors such as the patients' age, the nature of the affection, the degree of cardiac insufficiency, the standing of auricular fibrillation are not decisive in determining indications and contraindication for electric stimulation therapy. A considerable worsening of the cardiac dynamics with developing fibrillation arrhythmia, especially in patients suffering from cardiosclerosis, and a distinct improvement of the polycardiographic indices after defibrillation point to the need of attempting, whenever this is possible, to bar the auricular fibrillation. A pretreatment with potassium preparations and lengthy maintenance therapy with quinidine or quinidine-like agents is recommended. An analysis of the ECG findings after the electric stimulation therapy (heart rate, and its regularity, the state of the intraatrial and atrioventricular conduction) enable it to foresee the retention time of the re-established rhythm."}
{"id": "PMID:235038", "title": "Cationic proteins of human granulocytes. IV. Esterase activity.", "content": "The purfied antibacterial cationic proteins 1 to 7 (component 1 being the most cationic) of human neutrophil granulocytes have been assayed for enzyme activities. Components 1 to 4 and component 7 exhibited activities on tyrosine esters indicating a chymotrypsin-like activity with a neutral pH optimum. The inhibition of the esterase activity by diisopropyl fluorophosphate and phenylmethyl sulfonylfuoride also indicated the similarity to chymotrypsin, with a serine residue in the active center. In addition, the cationic proteins attacked complex substrates like casein and fibrinogen, suggesting a true proteolytic activity. Since the esterase activity of these proteins is heat-labile but the antibacterial activity against Staphylococcus aureus is heat-stable, it is concluded that the chymotrypsin-like activity is not essential for the microbicidal activity. There is evidence to suggest that the cationic proteins of human granulocytes are present in the cytoplasmic granules and exhibit antibacterial activity after release to the phagocytic vacuole and that, after extrusion from the cell, the proteins might be involved in the mediation of the inflammatory process due to enzyme and cationic activities.", "contents": "Cationic proteins of human granulocytes. IV. Esterase activity. The purfied antibacterial cationic proteins 1 to 7 (component 1 being the most cationic) of human neutrophil granulocytes have been assayed for enzyme activities. Components 1 to 4 and component 7 exhibited activities on tyrosine esters indicating a chymotrypsin-like activity with a neutral pH optimum. The inhibition of the esterase activity by diisopropyl fluorophosphate and phenylmethyl sulfonylfuoride also indicated the similarity to chymotrypsin, with a serine residue in the active center. In addition, the cationic proteins attacked complex substrates like casein and fibrinogen, suggesting a true proteolytic activity. Since the esterase activity of these proteins is heat-labile but the antibacterial activity against Staphylococcus aureus is heat-stable, it is concluded that the chymotrypsin-like activity is not essential for the microbicidal activity. There is evidence to suggest that the cationic proteins of human granulocytes are present in the cytoplasmic granules and exhibit antibacterial activity after release to the phagocytic vacuole and that, after extrusion from the cell, the proteins might be involved in the mediation of the inflammatory process due to enzyme and cationic activities."}
{"id": "PMID:235044", "title": "Variable-column bubble oxygenator. A new system for bubble oxygenation.", "content": "A new bubble oxygenator has been developed. Its main advantage is that the dimensions of the oxygenating chamber can be varied. Thus, the capacity for oxygenation may be adapted to different patients. It was used in 2,700 open-heart operations performed at the Institut do Corac\u00e3o, Faculdade de Medicina, Universidade de S\u00e3o Paulo, between January, 1971, and December, 1973. A group of 50 patients were subjected to more detailed studies. We found that the average hemolysis was 38.67 mg. per cent with a mean perfusion duration of 69 minutes, 38 seconds. Fibrinogen and platelet concentrations decreased by 14 and 25 per cent, respectively. The pH, PcO2, PO2, and base excess before and after cardiopulmonary bypass ranged within normal levels, and oxygenation (PO2) was always satisfactory.", "contents": "Variable-column bubble oxygenator. A new system for bubble oxygenation. A new bubble oxygenator has been developed. Its main advantage is that the dimensions of the oxygenating chamber can be varied. Thus, the capacity for oxygenation may be adapted to different patients. It was used in 2,700 open-heart operations performed at the Institut do Corac\u00e3o, Faculdade de Medicina, Universidade de S\u00e3o Paulo, between January, 1971, and December, 1973. A group of 50 patients were subjected to more detailed studies. We found that the average hemolysis was 38.67 mg. per cent with a mean perfusion duration of 69 minutes, 38 seconds. Fibrinogen and platelet concentrations decreased by 14 and 25 per cent, respectively. The pH, PcO2, PO2, and base excess before and after cardiopulmonary bypass ranged within normal levels, and oxygenation (PO2) was always satisfactory."}
{"id": "PMID:235045", "title": "[Burns combined with mechanical trauma].", "content": "On the basis of several years' material the mechanical lesions combined with burns are analysed by the authors and the diagnostical and therapeutical problems are dealt with. On the basis of their experiences it is pointed out that in the case of primary surgical management the reciprocal aggravating effect does not develop. Even in second-degree burned area primary healing of the suture following the wound excision has been observed. Extension treatment of the fracture is but rarely successful, the ideal method is the stable osteosynthesis.", "contents": "[Burns combined with mechanical trauma]. On the basis of several years' material the mechanical lesions combined with burns are analysed by the authors and the diagnostical and therapeutical problems are dealt with. On the basis of their experiences it is pointed out that in the case of primary surgical management the reciprocal aggravating effect does not develop. Even in second-degree burned area primary healing of the suture following the wound excision has been observed. Extension treatment of the fracture is but rarely successful, the ideal method is the stable osteosynthesis."}
{"id": "PMID:235046", "title": "[Primary management of injuries to the lateral ligament of the knee joint].", "content": "A long-used method: the primary suture of the lesions of the collateral ligaments of the knee joint is discussed by the authors. Because of the unsatisfactory results this method did not become a routine procedure. On the basis of their 24 cases the method is recommended by the authors. Atraumatic operative technique and the importance of the post-operative treatment are emphasized by the authors.", "contents": "[Primary management of injuries to the lateral ligament of the knee joint]. A long-used method: the primary suture of the lesions of the collateral ligaments of the knee joint is discussed by the authors. Because of the unsatisfactory results this method did not become a routine procedure. On the basis of their 24 cases the method is recommended by the authors. Atraumatic operative technique and the importance of the post-operative treatment are emphasized by the authors."}
{"id": "PMID:235047", "title": "[Injuries of the cervical spine].", "content": "In connection with 44 patients, who suffered injuries of the cervical spine, the types of the fracture and dislocation of the cervical spine are discussed. The injuries of the cervical spine--with or without injury of the spinal marrow--signify hard tast in respect of therapy. The conservative (extension) treatment of surgical intervention are even nowadays much debated themes in the neurosurgery. The introduction of Crutchfield tongs was a definite advance in the latter years. With this treatment method the restitution of the form, continuity and stability of the cervical spine is possible. In the opinion of the authors, surgical intervention (laminectomy) is necessary only in the case of progressive symptoms of compression of the cervival marrow (liquorstop). The survival of the patients depends often on the quick and proper treatment. The prevention of complications and the quick elimination are of great importance. Safeguarding of the physical and psychical conditions of the patients is the essential requirement of their rehabilitation after injuries of the cervical spine.", "contents": "[Injuries of the cervical spine]. In connection with 44 patients, who suffered injuries of the cervical spine, the types of the fracture and dislocation of the cervical spine are discussed. The injuries of the cervical spine--with or without injury of the spinal marrow--signify hard tast in respect of therapy. The conservative (extension) treatment of surgical intervention are even nowadays much debated themes in the neurosurgery. The introduction of Crutchfield tongs was a definite advance in the latter years. With this treatment method the restitution of the form, continuity and stability of the cervical spine is possible. In the opinion of the authors, surgical intervention (laminectomy) is necessary only in the case of progressive symptoms of compression of the cervival marrow (liquorstop). The survival of the patients depends often on the quick and proper treatment. The prevention of complications and the quick elimination are of great importance. Safeguarding of the physical and psychical conditions of the patients is the essential requirement of their rehabilitation after injuries of the cervical spine."}
{"id": "PMID:235048", "title": "[Avascular necrosis of the humeral head].", "content": "On the basis of observed cases the avascular necrosis of the head of the upper arm is discussed. After the lesion occurred on the proximal end of the humerus this late complication is not to be excluded. Besides the roentgenological signs, in the authors' opinion, the \"free interval\" in the patients' complaints may be of the greatest importance. The disturbance of the blood supply of the fractured piece of the upper arm may be responsible for the protracted recovery, in certain cases even for the lasting limitation of motion. No surgical treatment has been performed in the authors' cases.", "contents": "[Avascular necrosis of the humeral head]. On the basis of observed cases the avascular necrosis of the head of the upper arm is discussed. After the lesion occurred on the proximal end of the humerus this late complication is not to be excluded. Besides the roentgenological signs, in the authors' opinion, the \"free interval\" in the patients' complaints may be of the greatest importance. The disturbance of the blood supply of the fractured piece of the upper arm may be responsible for the protracted recovery, in certain cases even for the lasting limitation of motion. No surgical treatment has been performed in the authors' cases."}
{"id": "PMID:235049", "title": "[Congenital shoulder dysplasia and luxation].", "content": "In connection with the demonstration of their cases the congenital dysplasia and luxation of the shoulder are discussed. The theories in respect of the pathogenesis of this rare clinical picture, the differential diagnosis as well as the therapeutical possibilities are resumed.", "contents": "[Congenital shoulder dysplasia and luxation]. In connection with the demonstration of their cases the congenital dysplasia and luxation of the shoulder are discussed. The theories in respect of the pathogenesis of this rare clinical picture, the differential diagnosis as well as the therapeutical possibilities are resumed."}
{"id": "PMID:235050", "title": "[Substitution of the tendon sheath by autologous vein in the \"no-man's land\" of the hand].", "content": "Reconstructive surgical interventions on the level of the proximal phalanges and performed after the lesions of the flexor tendons on the distal palm are discussed. In order to reduce the adhesions \"bridging of the no man's land\" by means of an autotransplanted vein is recommended by the authors. The vein-graft cannulated on a silicone bar is embedded within a few weeks, and after the removal of the silicone the \"no man's land\" is \"over-bridged\" by a pseudotendon sheath, stuffed with endothelium of good sliding surface. Thus, in the second sitting each of the plastic \"bridge\" methods (Bunnell, Paneva--Holevitch) may be performed. The operative technique and the first 4 cases are shortly discussed by the authors.", "contents": "[Substitution of the tendon sheath by autologous vein in the \"no-man's land\" of the hand]. Reconstructive surgical interventions on the level of the proximal phalanges and performed after the lesions of the flexor tendons on the distal palm are discussed. In order to reduce the adhesions \"bridging of the no man's land\" by means of an autotransplanted vein is recommended by the authors. The vein-graft cannulated on a silicone bar is embedded within a few weeks, and after the removal of the silicone the \"no man's land\" is \"over-bridged\" by a pseudotendon sheath, stuffed with endothelium of good sliding surface. Thus, in the second sitting each of the plastic \"bridge\" methods (Bunnell, Paneva--Holevitch) may be performed. The operative technique and the first 4 cases are shortly discussed by the authors."}
{"id": "PMID:235051", "title": "[Ultrastructural changes in human skeletal muscles following tendon and nerve injuries. I. Ultrastructural changes following tendon injuries].", "content": "During reconstructive procedures performed 4-16 weeks after the tendon lesion the specimens obtained from the injured muscle have been examined by the authors. It was found that after the tendon injury inactivity atrophy develops and a condition of equilibrium could be observed at this time. The most important changes in the fine structure were seen in the contractile elements: these were atrophied, homogenized, fragmentated and ragged independently from the functional unities. The number of the mitochondria was considerably decreased, the sarcoplasmic reticulum was increased, and the difference between the originally red and white muscular fibres was indistinct. The glycogen content of the musculature was decreased, or it disappeared completely. No pathologic changes have been observed in the sarcolemma, the cell nuclei and the motor nerve end-organs.", "contents": "[Ultrastructural changes in human skeletal muscles following tendon and nerve injuries. I. Ultrastructural changes following tendon injuries]. During reconstructive procedures performed 4-16 weeks after the tendon lesion the specimens obtained from the injured muscle have been examined by the authors. It was found that after the tendon injury inactivity atrophy develops and a condition of equilibrium could be observed at this time. The most important changes in the fine structure were seen in the contractile elements: these were atrophied, homogenized, fragmentated and ragged independently from the functional unities. The number of the mitochondria was considerably decreased, the sarcoplasmic reticulum was increased, and the difference between the originally red and white muscular fibres was indistinct. The glycogen content of the musculature was decreased, or it disappeared completely. No pathologic changes have been observed in the sarcolemma, the cell nuclei and the motor nerve end-organs."}
{"id": "PMID:235052", "title": "[Treatment of sternum fractures].", "content": "The frequency and the treatment of the sternal fractures is discussed by the authors. 5 patients with sternal fractures have been treated by the authors, and 3 of them were operated on. In one patient early operation has been performed, and in another the osteosynthesis of the sternum has been carried out 3 years after the lesion. In the 3d patient the bone piece broken down from the sternum damaged the arteria mammaria int. sin., necessitating thus surgical intervention.", "contents": "[Treatment of sternum fractures]. The frequency and the treatment of the sternal fractures is discussed by the authors. 5 patients with sternal fractures have been treated by the authors, and 3 of them were operated on. In one patient early operation has been performed, and in another the osteosynthesis of the sternum has been carried out 3 years after the lesion. In the 3d patient the bone piece broken down from the sternum damaged the arteria mammaria int. sin., necessitating thus surgical intervention."}
{"id": "PMID:235053", "title": "[Unusual self mutilation with the purpose of obtaining illegal insurance benefits].", "content": "In this unusual form of self mutilation the fracture of the phalanx has been carried out--upon request--by foreign person (inderect self mutilation), in order to obtain illegal accident insurance money. Short survey of the relevant literature is given and the possibilities are outlined, which facilitate at the primary wound dressing the establishment of suspicious cases.", "contents": "[Unusual self mutilation with the purpose of obtaining illegal insurance benefits]. In this unusual form of self mutilation the fracture of the phalanx has been carried out--upon request--by foreign person (inderect self mutilation), in order to obtain illegal accident insurance money. Short survey of the relevant literature is given and the possibilities are outlined, which facilitate at the primary wound dressing the establishment of suspicious cases."}
{"id": "PMID:235054", "title": "[Total luxation of the ankle, without fracture].", "content": "In the 4 and 10 years' material of two Surgical Departments four total luxations of the talus--without fracture--have been observed by the authors. This luxation is a very rare lesion. The authors' cases are described in detail. All patients heald without complications. The Hungarian and foreign literature dealing with isolated talus luxation is reviewed in detail. The biomechanics, the problems of diagnosis and the treatment are discussed.", "contents": "[Total luxation of the ankle, without fracture]. In the 4 and 10 years' material of two Surgical Departments four total luxations of the talus--without fracture--have been observed by the authors. This luxation is a very rare lesion. The authors' cases are described in detail. All patients heald without complications. The Hungarian and foreign literature dealing with isolated talus luxation is reviewed in detail. The biomechanics, the problems of diagnosis and the treatment are discussed."}
{"id": "PMID:235062", "title": "Renal vascular tone in essential and secondary hypertension: hemodynamic and angiographic responses to vasodilators.", "content": "The renal vascular response to graded doses of acetylcholine, dopamine and phentolamine, assessed by xenon washout and selective arteriography was used to define the relative contribution of fixed and reversible vascular abnormalities to increased renal vascular resistance in patients with essential or secondary hypertension. The increase in blood flow induced by acetylcholine and dopamine was blunted strikingly in patients with advanced nephrosclerosis, chronic pyelonephritis and polycystic kidney disease and was normal in the kidney contralateral to a significant renal artery stenosis. Conversely, the response to both was potentiated in 9 of 13 (69%) patients with mild essential hypertension. Equivalent potentiation of the response to acetylcholine was induced in normal subjects by increasing renal vascular tone pharmacologically with angiotensin. Phentolamine infused into the renal artery also increased renal blood flow significantly in 6 of 9 (67%) patients with mild essential hypertension, but in none of 15 normal subjects, over a dose reange that paralleled that for alpha-adrenergic blockade. Changes in the selective renal arteriogram were in excellent accord: potentiated response to acetylcholine, phentolamine or dopamine was associated with reversal of the small vessel abnormalities visualized in the arteriogram. The reduced blood flow response in advanced nephrosclerosis or parenchymal disease was associated with a reduced angiographic change during dilator infusion. The results suggest a quantitatively important, functional renal vascular abnormality--perhaps mediated by the sympathetic nervous system--in many patients with mild essential hypertension. Conversely the renal vascular abnormality associated with advanced nephrosclerosis or renal parenchymal disease is largely fixed and is probably due to organic changes.", "contents": "Renal vascular tone in essential and secondary hypertension: hemodynamic and angiographic responses to vasodilators. The renal vascular response to graded doses of acetylcholine, dopamine and phentolamine, assessed by xenon washout and selective arteriography was used to define the relative contribution of fixed and reversible vascular abnormalities to increased renal vascular resistance in patients with essential or secondary hypertension. The increase in blood flow induced by acetylcholine and dopamine was blunted strikingly in patients with advanced nephrosclerosis, chronic pyelonephritis and polycystic kidney disease and was normal in the kidney contralateral to a significant renal artery stenosis. Conversely, the response to both was potentiated in 9 of 13 (69%) patients with mild essential hypertension. Equivalent potentiation of the response to acetylcholine was induced in normal subjects by increasing renal vascular tone pharmacologically with angiotensin. Phentolamine infused into the renal artery also increased renal blood flow significantly in 6 of 9 (67%) patients with mild essential hypertension, but in none of 15 normal subjects, over a dose reange that paralleled that for alpha-adrenergic blockade. Changes in the selective renal arteriogram were in excellent accord: potentiated response to acetylcholine, phentolamine or dopamine was associated with reversal of the small vessel abnormalities visualized in the arteriogram. The reduced blood flow response in advanced nephrosclerosis or parenchymal disease was associated with a reduced angiographic change during dilator infusion. The results suggest a quantitatively important, functional renal vascular abnormality--perhaps mediated by the sympathetic nervous system--in many patients with mild essential hypertension. Conversely the renal vascular abnormality associated with advanced nephrosclerosis or renal parenchymal disease is largely fixed and is probably due to organic changes."}
{"id": "PMID:235063", "title": "Late failure or human renal transplants. An analysis of transplant disease and graft failure among 125 recipients surviving for one to eight years.", "content": "The purpose of the present paper was to study clinical, morphological and immunological aspects of late rejection of renal allotransplants. We have, therefore, analyzed the occurrence and nature of renal transplant disease and graft failure among 125 recipients surviving for 1 to more than 8 years after transplantation. In this population transplant disease as defined by the appearance of heavy proteinuria and/or steadily declining graft function occurred in 22 patients. At the closure date of the study on December 31, 1972 complete graft failure had occurred in 12 of these 22 patients and 4 of these have died. In addition two patients died in the presence of normal graft function, due to chronic hepatitis and metastatic cancer respectively. As based on clinical findings, pathophysiological features and renal lesions the patients with late transplant disease were classified into two groups and described accordingly. Group A, termed glomerular transplant disease, included a majority of 16 patients, constituting a rather homogenous idsease entity in relation to course of disease, clinical findings and renal lesions as studied by light-, immunofluorescence- and electron microscopy. All these patients presented with heavy proteinuria, which was non-selective in all but two, resulting eventually in complete loss of graft function in eight cases. All these patients developed hypoalbuminemia and hypercholesterolemia, and one half manifested a classical nephrotic syndrome. Arterial hypertension occurred in all patients except two. Glomerular structure as studied by light microscopy revealed a number of lesions of a rather polymorphous pattern in all patients in group A. Endomesangial proliferation, hyperplasia and segmental proliferation of epithelial cells and thickening of capillary walls were prominent features, although the degree of severity, extension and type of lesion occurred in such varying proportions that classification into any well characterized category of glomerulonephritis was not possible. All cases in group A revealed immune deposits, most frequently containing IgG, IgM, complement and fibrinogen. IgA, IgD and IgE were also demonstrated in a lesser proportion of cases in this group. The immunofluorescent pattern was a mixed granular and linear, and in no case strictly linear or granular alone. The ultrastructural investigation contains a detailed analysis of the", "contents": "Late failure or human renal transplants. An analysis of transplant disease and graft failure among 125 recipients surviving for one to eight years. The purpose of the present paper was to study clinical, morphological and immunological aspects of late rejection of renal allotransplants. We have, therefore, analyzed the occurrence and nature of renal transplant disease and graft failure among 125 recipients surviving for 1 to more than 8 years after transplantation. In this population transplant disease as defined by the appearance of heavy proteinuria and/or steadily declining graft function occurred in 22 patients. At the closure date of the study on December 31, 1972 complete graft failure had occurred in 12 of these 22 patients and 4 of these have died. In addition two patients died in the presence of normal graft function, due to chronic hepatitis and metastatic cancer respectively. As based on clinical findings, pathophysiological features and renal lesions the patients with late transplant disease were classified into two groups and described accordingly. Group A, termed glomerular transplant disease, included a majority of 16 patients, constituting a rather homogenous idsease entity in relation to course of disease, clinical findings and renal lesions as studied by light-, immunofluorescence- and electron microscopy. All these patients presented with heavy proteinuria, which was non-selective in all but two, resulting eventually in complete loss of graft function in eight cases. All these patients developed hypoalbuminemia and hypercholesterolemia, and one half manifested a classical nephrotic syndrome. Arterial hypertension occurred in all patients except two. Glomerular structure as studied by light microscopy revealed a number of lesions of a rather polymorphous pattern in all patients in group A. Endomesangial proliferation, hyperplasia and segmental proliferation of epithelial cells and thickening of capillary walls were prominent features, although the degree of severity, extension and type of lesion occurred in such varying proportions that classification into any well characterized category of glomerulonephritis was not possible. All cases in group A revealed immune deposits, most frequently containing IgG, IgM, complement and fibrinogen. IgA, IgD and IgE were also demonstrated in a lesser proportion of cases in this group. The immunofluorescent pattern was a mixed granular and linear, and in no case strictly linear or granular alone. The ultrastructural investigation contains a detailed analysis of the"}
{"id": "PMID:235084", "title": "[The significance of histochemical demonstration of oxidative enzymes in the interpretation of local and remote effects of experimental brain lesions].", "content": "In cortex, habenular- or hypothalamic regions of white rats electrocoagulation was carried out. Animals were killed from 6 days to 5 months after the operation. Serial slides of the brain were investigated by the aid of a reaction of SDH, alfa-GPDH, LDH, G6PDH, TPND. Group of neurons around the lesion may show a decreased, normal and increased activity of the enzymes investigated. As for the far effect of the lesion in case of the injury of the postcomissural fornix changes could have to be revealed in the corpus mamillare. Activization of neuroglia is marked by the increase of the reaction of G6PDH, LDH and TPNDH. Enzyme activity of cells of microglial origin at the beginning seems to be significant, later on, when the activity of phagocytes comes to the end it decreases to the minimum. Regeneration of cells of the leptomeninges and their role in demarcation of the process is marked by the increase of enzyme activity.", "contents": "[The significance of histochemical demonstration of oxidative enzymes in the interpretation of local and remote effects of experimental brain lesions]. In cortex, habenular- or hypothalamic regions of white rats electrocoagulation was carried out. Animals were killed from 6 days to 5 months after the operation. Serial slides of the brain were investigated by the aid of a reaction of SDH, alfa-GPDH, LDH, G6PDH, TPND. Group of neurons around the lesion may show a decreased, normal and increased activity of the enzymes investigated. As for the far effect of the lesion in case of the injury of the postcomissural fornix changes could have to be revealed in the corpus mamillare. Activization of neuroglia is marked by the increase of the reaction of G6PDH, LDH and TPNDH. Enzyme activity of cells of microglial origin at the beginning seems to be significant, later on, when the activity of phagocytes comes to the end it decreases to the minimum. Regeneration of cells of the leptomeninges and their role in demarcation of the process is marked by the increase of enzyme activity."}
{"id": "PMID:235085", "title": "[Diagnosis of pancreatic function by the selenomethionine--75Se test].", "content": "Dterminations of 75selenium radioactivity and pancreatic enzyme in duodenal aspirate were carried out in 50 patients after i. v. injection of selenomethionine-75Se.  After standardized excitation of the pancreas with pancreozymin-secretin, a significant correlation (r = 0.654) between excreted 75Se radioactivity and trypsin production could be established.  The test is suitable for the recording of exocrine pancreas function while avoiding expensive enzymatic methods.  The combined use of pancreas scintigraphy--using the double radionuclide substraction technique-with the radioselenomethionine test (RSMT) provides comprehensive diagnostic information on the morphology and function of the pancreas.", "contents": "[Diagnosis of pancreatic function by the selenomethionine--75Se test]. Dterminations of 75selenium radioactivity and pancreatic enzyme in duodenal aspirate were carried out in 50 patients after i. v. injection of selenomethionine-75Se.  After standardized excitation of the pancreas with pancreozymin-secretin, a significant correlation (r = 0.654) between excreted 75Se radioactivity and trypsin production could be established.  The test is suitable for the recording of exocrine pancreas function while avoiding expensive enzymatic methods.  The combined use of pancreas scintigraphy--using the double radionuclide substraction technique-with the radioselenomethionine test (RSMT) provides comprehensive diagnostic information on the morphology and function of the pancreas."}
{"id": "PMID:235086", "title": "Procedures used in the induction of mitotic recombination and mutation in the yeast Saccharomyces cerevisiae.", "content": "Techniques are described for the use of various yeast strains to detect the induction of (1) mitotic crossing-over, (2) mitotic gene conversion, (3) forward mutation and (4) reverse mutation. The technique for the detection of mitotic crossing over is based on a diploid that carries two different alleles of the gene locus ade2. These alleles differ in their extent of colony pigmentation engendered on low-adenine media, and they complement each other to the effect that the diploid is white. Mitotic crossing over results in the formation of twin-sectored colonies with a red and a pink sector. The technique for the detection of mitotic gene conversion is based on the use of a heteroallelic diploid carrying two non-complementing alleles that cause a nutritional requirement. Mitotic gene conversion leads to the restoration of intact and dominant wild-type alleles that alleviate the nutritional requirement so that convertant cells can be selected on a minimal medium. The forward mutation technique is based on the use of a haploid strain with a defect in the ade2-gene locus which causes the formation of red colonies. Induction of forward mutation in a number of other loci prevents the accumulation of this red pigment so that induction of mutation can be detected by the formation of pink and white colonies. The reverse mutation technique is based on the restoration or compensation of a mutational defect causing a growth requirement. Mutants can be selected for on a minimal medium.", "contents": "Procedures used in the induction of mitotic recombination and mutation in the yeast Saccharomyces cerevisiae. Techniques are described for the use of various yeast strains to detect the induction of (1) mitotic crossing-over, (2) mitotic gene conversion, (3) forward mutation and (4) reverse mutation. The technique for the detection of mitotic crossing over is based on a diploid that carries two different alleles of the gene locus ade2. These alleles differ in their extent of colony pigmentation engendered on low-adenine media, and they complement each other to the effect that the diploid is white. Mitotic crossing over results in the formation of twin-sectored colonies with a red and a pink sector. The technique for the detection of mitotic gene conversion is based on the use of a heteroallelic diploid carrying two non-complementing alleles that cause a nutritional requirement. Mitotic gene conversion leads to the restoration of intact and dominant wild-type alleles that alleviate the nutritional requirement so that convertant cells can be selected on a minimal medium. The forward mutation technique is based on the use of a haploid strain with a defect in the ade2-gene locus which causes the formation of red colonies. Induction of forward mutation in a number of other loci prevents the accumulation of this red pigment so that induction of mutation can be detected by the formation of pink and white colonies. The reverse mutation technique is based on the restoration or compensation of a mutational defect causing a growth requirement. Mutants can be selected for on a minimal medium."}
{"id": "PMID:235087", "title": "Microsomal activation to mutagens of antischistosomal methyl thioxanthenones and initial tests on a possibly non-mutagenic analogue.", "content": "Five methylthioxanthenone and methylbenzothiopyranoindazole analogues, including lucanthone (Miracil D), are non-mutagenic for Salmonella typhimurium but are activated to mutagens by a rat liver microsome preparation. Hydroxymethyl analogues, including hycathone (Etrenol), are mutagenic in the absence of microsomes. It seems reasonable to assume that the hydroxymethyl derivatives are the more proximal mutagens and that Salmonella is unable to carry out the hydroxylation necessary for mutagen activation. During the pase 24 years, several million patients with schistosomiasis have been treated with lucanthone, and in recent years about 700 000 persons with hycanthone. The possible long-term deleterious effects of these agents for man even now remain to be determined. Our studies indicate that particular modifications in the structure of thioxanthenones drastically alter their mutagenicity. One apparently non-mutagenic thioxanthenone has been found. A number of the less mutagenic compounds also exhibit decreased acute toxicity in the mouse while retaining appreciable antischistosomal activity, suggesting that genetic and schistosomicidal activities may be dissociated from each other.", "contents": "Microsomal activation to mutagens of antischistosomal methyl thioxanthenones and initial tests on a possibly non-mutagenic analogue. Five methylthioxanthenone and methylbenzothiopyranoindazole analogues, including lucanthone (Miracil D), are non-mutagenic for Salmonella typhimurium but are activated to mutagens by a rat liver microsome preparation. Hydroxymethyl analogues, including hycathone (Etrenol), are mutagenic in the absence of microsomes. It seems reasonable to assume that the hydroxymethyl derivatives are the more proximal mutagens and that Salmonella is unable to carry out the hydroxylation necessary for mutagen activation. During the pase 24 years, several million patients with schistosomiasis have been treated with lucanthone, and in recent years about 700 000 persons with hycanthone. The possible long-term deleterious effects of these agents for man even now remain to be determined. Our studies indicate that particular modifications in the structure of thioxanthenones drastically alter their mutagenicity. One apparently non-mutagenic thioxanthenone has been found. A number of the less mutagenic compounds also exhibit decreased acute toxicity in the mouse while retaining appreciable antischistosomal activity, suggesting that genetic and schistosomicidal activities may be dissociated from each other."}
{"id": "PMID:235089", "title": "Evaluation of patient-care protocol use by various providers.", "content": "A symptom-oriented protocol for acute pharyngitis was evaluated in a busy general medical clinic staffed by physicians and graduate and student physician's assistants. We observed significantly improved performance by all providers in collection of medical data, utilization of laboratory tests,and appropriate use of antibiotics after introduction of the protocol. Patient charges were less when the protocol was used, but these savings were offset partially by the cost of audit. Compliance with and acceptance of the protocol differed among the various health providers, with physicians demonstrating significantly lower levels than nonphysicians. Patient-care protocols provide an effective means of monitoring the process of medical care, detecting weakness in supportive clinic services, and affording educational feedback for all health providers.", "contents": "Evaluation of patient-care protocol use by various providers. A symptom-oriented protocol for acute pharyngitis was evaluated in a busy general medical clinic staffed by physicians and graduate and student physician's assistants. We observed significantly improved performance by all providers in collection of medical data, utilization of laboratory tests,and appropriate use of antibiotics after introduction of the protocol. Patient charges were less when the protocol was used, but these savings were offset partially by the cost of audit. Compliance with and acceptance of the protocol differed among the various health providers, with physicians demonstrating significantly lower levels than nonphysicians. Patient-care protocols provide an effective means of monitoring the process of medical care, detecting weakness in supportive clinic services, and affording educational feedback for all health providers."}
{"id": "PMID:235090", "title": "Use of an angiotensin II antagonist (saralasin) in the recognition of \"angiotensinogenic\" hypertension;.", "content": "The possibility has been explored of using a specific angiotensin ii antagonist, saralasin (P-113, 1-sar-8-ala-angiotensin ii) to recognize patients whose hypertension depends upon excessive angiotensin ii activity.  Among 60 hypertensive patients, saralasin infusion reduced blood pressure in 16 \"responders,\" but not in 44 \"nonresponders.\" The \"responders\" had the following findings: elevated plasma renin activity in renal vein (or veins) or peripheral veins or both (16 of 16); reduced renal blood flow, shown by arteriography, isotopic studies or pyelography (15 or 16), or progressive azotemia (one of 16); and reduction in blood. These findings indicated that angiotensin ii probably caused hypertension in the \"responders,\" One \"nonresponder\" had renal vein levels of plasma renin activity suggestive of angiotensinogenic hypertension.  Since hypertension was invariably angiotensinogenic when it was reduced by saralasin and, with one possible exception, was never angiotensinogenic in \"nonresponders,\" the antagonist appears to provide an efpressure to or toward normal after corrective operation (four of four) or propranolol therapy (eight of eight). fective means of recognizing angiotensinogenic hypertension.", "contents": "Use of an angiotensin II antagonist (saralasin) in the recognition of \"angiotensinogenic\" hypertension;. The possibility has been explored of using a specific angiotensin ii antagonist, saralasin (P-113, 1-sar-8-ala-angiotensin ii) to recognize patients whose hypertension depends upon excessive angiotensin ii activity.  Among 60 hypertensive patients, saralasin infusion reduced blood pressure in 16 \"responders,\" but not in 44 \"nonresponders.\" The \"responders\" had the following findings: elevated plasma renin activity in renal vein (or veins) or peripheral veins or both (16 of 16); reduced renal blood flow, shown by arteriography, isotopic studies or pyelography (15 or 16), or progressive azotemia (one of 16); and reduction in blood. These findings indicated that angiotensin ii probably caused hypertension in the \"responders,\" One \"nonresponder\" had renal vein levels of plasma renin activity suggestive of angiotensinogenic hypertension.  Since hypertension was invariably angiotensinogenic when it was reduced by saralasin and, with one possible exception, was never angiotensinogenic in \"nonresponders,\" the antagonist appears to provide an efpressure to or toward normal after corrective operation (four of four) or propranolol therapy (eight of eight). fective means of recognizing angiotensinogenic hypertension."}
{"id": "PMID:235094", "title": "Medical education in China in the postcultural Revolution era.", "content": "The Cultural Revolution has had an important impact on Chinese medical education. The Chinese system is engaged in a vigorous program to solve health-manpower needs in the rural areas by emphasizing de-professionalization, mass orientation and accountability to the community. Among the notable changes within the medical schools are the following: an admission process favoring the recruitment of peasants, factory workers, and the military; a three-year program with heavy emphasis on practicing in rural communities; widespread integration of the traditional Chinese and Western systems of medical practice; and manual labor and political seminars, which compose more than 25 per cent of the required curriculum. These innovations have been greatly facilitated by a strong national commitment and supportive political system. The fact that less than 10 per cent of doctors in China today are graduates of college-level medical education indicates the importance of other entry possibilities.", "contents": "Medical education in China in the postcultural Revolution era. The Cultural Revolution has had an important impact on Chinese medical education. The Chinese system is engaged in a vigorous program to solve health-manpower needs in the rural areas by emphasizing de-professionalization, mass orientation and accountability to the community. Among the notable changes within the medical schools are the following: an admission process favoring the recruitment of peasants, factory workers, and the military; a three-year program with heavy emphasis on practicing in rural communities; widespread integration of the traditional Chinese and Western systems of medical practice; and manual labor and political seminars, which compose more than 25 per cent of the required curriculum. These innovations have been greatly facilitated by a strong national commitment and supportive political system. The fact that less than 10 per cent of doctors in China today are graduates of college-level medical education indicates the importance of other entry possibilities."}
{"id": "PMID:235101", "title": "Studies on the synthesis and subcellular distribution of dopamine in the rat adrenal medulla.", "content": "Rats received intravenous injections of 3H-tyrosine and were killed at various time intervals thereafter. 3H-dopamine (DA) in the adrenals reached a maximum within 1.5 min after the administration of 3h=tyrosine. From the 15th min it disappeared with an apparent half life of 90 min. 3H-Adrenaline (A) plus 3H-noradrenaline(NA) increased much more slowly and reached a plateau 120-240 min after the injection. The approximate synthesis rate of adrenal A plus NA, calculated from the specific activity curves, ranged from 0.3 to 2.2 nmoles/h per kg b.w. The highest value was noted the first few minutes, the lowest 1-2 hrs after the administration of 3H-tyrosine. In some experiments subcellular fractionation of the adrenals was performed. In untreated animals the amount of DA and A plus NA recovered from the supernatant fraction was about 10 and 8 per cent, respectively, of the total amount recovered from the supernatant and particulate fractions. In the adrenals of animals receiving 3H-tyrosine 3.75 or 60 min beforehand these figures were significantly elevated whereas the DA and A plus NA of the particulate fraction did not deviate significantly from control values. The specific activities of 3H-DA were the same in the supernatant and particulate fractions within 3.75 min after the injection of 3H-tyrosine.", "contents": "Studies on the synthesis and subcellular distribution of dopamine in the rat adrenal medulla. Rats received intravenous injections of 3H-tyrosine and were killed at various time intervals thereafter. 3H-dopamine (DA) in the adrenals reached a maximum within 1.5 min after the administration of 3h=tyrosine. From the 15th min it disappeared with an apparent half life of 90 min. 3H-Adrenaline (A) plus 3H-noradrenaline(NA) increased much more slowly and reached a plateau 120-240 min after the injection. The approximate synthesis rate of adrenal A plus NA, calculated from the specific activity curves, ranged from 0.3 to 2.2 nmoles/h per kg b.w. The highest value was noted the first few minutes, the lowest 1-2 hrs after the administration of 3H-tyrosine. In some experiments subcellular fractionation of the adrenals was performed. In untreated animals the amount of DA and A plus NA recovered from the supernatant fraction was about 10 and 8 per cent, respectively, of the total amount recovered from the supernatant and particulate fractions. In the adrenals of animals receiving 3H-tyrosine 3.75 or 60 min beforehand these figures were significantly elevated whereas the DA and A plus NA of the particulate fraction did not deviate significantly from control values. The specific activities of 3H-DA were the same in the supernatant and particulate fractions within 3.75 min after the injection of 3H-tyrosine."}
{"id": "PMID:235102", "title": "Apparent equilibrium constant between beta-adrenoceptors and a competitive antagonist on a cultured pacemaker cell of mammalian heart.", "content": "Heart cells from newborn rats and kittens were cultured.  In both species the rate of pacemaker activity of single, cultured cells was increased by low concentrations of catecholamines.  Tthe beta-adrenoceptor blocker (minus)-KL255 antagonized competitively the effects of both, (minus)-noradrenaline and (minus)-isoprenaline.  A mean equilibrium constant of 3.6 times 10-10M between (minus)-KL255 and beta-adrenoceptors of single cells was estimated.", "contents": "Apparent equilibrium constant between beta-adrenoceptors and a competitive antagonist on a cultured pacemaker cell of mammalian heart. Heart cells from newborn rats and kittens were cultured.  In both species the rate of pacemaker activity of single, cultured cells was increased by low concentrations of catecholamines.  Tthe beta-adrenoceptor blocker (minus)-KL255 antagonized competitively the effects of both, (minus)-noradrenaline and (minus)-isoprenaline.  A mean equilibrium constant of 3.6 times 10-10M between (minus)-KL255 and beta-adrenoceptors of single cells was estimated."}
{"id": "PMID:235104", "title": "Variation in pH of plaque after a mouth rinse with a saturated solution of mannitol.", "content": "Plaque pH changes were studied in a group of 18 persons after a mouth rinse for 30 seconds with a 50 per cent (w/v) solution of sucrose. One week later the experiment was repeated on the same group of persons, but then with a saturated solution of mannitol instead of sucrose. Dental plaque material was collected from 15 different areas equally distributed among all the teeth. The changes in H-ion concentration in plaque were studied 2, 5, 10, 20, and 30 minutes after the rinse. Saturated mannitol caused an insignificant pH-increase at 2 minutes after which the pH-values remained unchanged. The sucrose (50 per cent) markedly lowered the pH-value, with the lowest value at 5 minutes, after which it slowly rose. The differences were highly significant at all intervals.", "contents": "Variation in pH of plaque after a mouth rinse with a saturated solution of mannitol. Plaque pH changes were studied in a group of 18 persons after a mouth rinse for 30 seconds with a 50 per cent (w/v) solution of sucrose. One week later the experiment was repeated on the same group of persons, but then with a saturated solution of mannitol instead of sucrose. Dental plaque material was collected from 15 different areas equally distributed among all the teeth. The changes in H-ion concentration in plaque were studied 2, 5, 10, 20, and 30 minutes after the rinse. Saturated mannitol caused an insignificant pH-increase at 2 minutes after which the pH-values remained unchanged. The sucrose (50 per cent) markedly lowered the pH-value, with the lowest value at 5 minutes, after which it slowly rose. The differences were highly significant at all intervals."}
{"id": "PMID:235105", "title": "Degradation of maltose and starch by human saliva and by supernatants of dental plaque material.", "content": "The pH-decrease in dental plaque in vivo after mouth rinses with solutions of sucrose and maltose has been compared. No statistically significant differences were found between the results obtained with these two disaccharides. Pooled samples of parotid saliva, centrifuged whole saliva and dental plaque supernatants were separated with the isoelectric focusing technique. The results suggest that maltose is hydrolysed in parotid saliva by the salivary alpha-amylase and in dental plaque by enzymes from sources other than the salivary glands, probably microorganisms. No bacterial alpha-amylases, separated from salivary alpha-amylase, were found in whole saliva specimens or in dental plaque supernatants. Quantitative determinations of \"maltase\" and amylase activities in parotid saliva, centrifuged whole saliva and dental plaque supernatants from 10 subjects were carried out. The highest enzyme activity of \"maltase\" was found in the samples of dental plaque and the highest amylase activity in parotid saliva specimens.", "contents": "Degradation of maltose and starch by human saliva and by supernatants of dental plaque material. The pH-decrease in dental plaque in vivo after mouth rinses with solutions of sucrose and maltose has been compared. No statistically significant differences were found between the results obtained with these two disaccharides. Pooled samples of parotid saliva, centrifuged whole saliva and dental plaque supernatants were separated with the isoelectric focusing technique. The results suggest that maltose is hydrolysed in parotid saliva by the salivary alpha-amylase and in dental plaque by enzymes from sources other than the salivary glands, probably microorganisms. No bacterial alpha-amylases, separated from salivary alpha-amylase, were found in whole saliva specimens or in dental plaque supernatants. Quantitative determinations of \"maltase\" and amylase activities in parotid saliva, centrifuged whole saliva and dental plaque supernatants from 10 subjects were carried out. The highest enzyme activity of \"maltase\" was found in the samples of dental plaque and the highest amylase activity in parotid saliva specimens."}
{"id": "PMID:235107", "title": "Mechanism of skin penetration by Ancylostoma tubaeforme larvae.", "content": "Skin penetration by infective Ancylostoma tubaeforme larvae has been investigated cinematographically and using in vitro techniques. The dermal tissue appears to cause little hinderance to larval migration but complete penetration through the skin from the dermal direction did not occur, although total penetration from the epidermal surface was frequently accomplished. No evidence could be found for enzymic secretions emanating from the worms under conditions that gave positive results from Necator americanus and Strongyloides f\u00fclleborni infective larvae. The results indicated that A. tubaeforme was able to penetrate without the use of enzymic secretions and an alternative, mechanical mechanism for penetration is advanced.", "contents": "Mechanism of skin penetration by Ancylostoma tubaeforme larvae. Skin penetration by infective Ancylostoma tubaeforme larvae has been investigated cinematographically and using in vitro techniques. The dermal tissue appears to cause little hinderance to larval migration but complete penetration through the skin from the dermal direction did not occur, although total penetration from the epidermal surface was frequently accomplished. No evidence could be found for enzymic secretions emanating from the worms under conditions that gave positive results from Necator americanus and Strongyloides f\u00fclleborni infective larvae. The results indicated that A. tubaeforme was able to penetrate without the use of enzymic secretions and an alternative, mechanical mechanism for penetration is advanced."}
{"id": "PMID:235108", "title": "Placental transfer and fetal urinary excretion of gentamicin during constant rate maternal infusion.", "content": "Placental transfer and fetal urinary excretion of gentamicin was studied in midtrimester goat and human previable fetuses during constant rate maternal infusion with the drug. Gentamicin was not detected in the serum of any of the goat fetuses, even when maternal serum concentrations ranged from 15.2 mug/ml to 20.9 mug/ml. However, gentamicin was present in the amniotic fluid of four animals. Gentamicin was also present in fetal urine collected from three animals. In contrast human fetal central venous serum concentrations of gentamicin were 21-37% of those in maternal serum after constant rate infusion of the mother. In addition, gentamicin was present in human fetal urine in concentrations 2-- 3 times those in fetal serum. The observed difference in fetal serum concentration of gentamicin between the two species represents a difference in placental permeability to gentamicin and/ or a difference in fetal renal clearance of the drug.", "contents": "Placental transfer and fetal urinary excretion of gentamicin during constant rate maternal infusion. Placental transfer and fetal urinary excretion of gentamicin was studied in midtrimester goat and human previable fetuses during constant rate maternal infusion with the drug. Gentamicin was not detected in the serum of any of the goat fetuses, even when maternal serum concentrations ranged from 15.2 mug/ml to 20.9 mug/ml. However, gentamicin was present in the amniotic fluid of four animals. Gentamicin was also present in fetal urine collected from three animals. In contrast human fetal central venous serum concentrations of gentamicin were 21-37% of those in maternal serum after constant rate infusion of the mother. In addition, gentamicin was present in human fetal urine in concentrations 2-- 3 times those in fetal serum. The observed difference in fetal serum concentration of gentamicin between the two species represents a difference in placental permeability to gentamicin and/ or a difference in fetal renal clearance of the drug."}
{"id": "PMID:235114", "title": "Blood sampling through umbilical catheters.", "content": "An in vitro study testing the reliability of chemical determinations on blood samples withdrawn through an umbilical catheter is described. Blood samples were withdrawn through three different sizes of umbilical catheters containing a solution of dextrose, sodium bicarbonate, and potassium. Using either a 5 French or a 3 1/2 French catheter, accurate results were obtained for pH, sodium, potassium, and glucose when measurements were made after an initial 4-ml blood sample was discarded. With an 8 French catheter, accurate results were obtained for pH, sodium, and potassium but plasma glucose determinations remained inaccurate after 6 ml of blood was discarded.", "contents": "Blood sampling through umbilical catheters. An in vitro study testing the reliability of chemical determinations on blood samples withdrawn through an umbilical catheter is described. Blood samples were withdrawn through three different sizes of umbilical catheters containing a solution of dextrose, sodium bicarbonate, and potassium. Using either a 5 French or a 3 1/2 French catheter, accurate results were obtained for pH, sodium, potassium, and glucose when measurements were made after an initial 4-ml blood sample was discarded. With an 8 French catheter, accurate results were obtained for pH, sodium, and potassium but plasma glucose determinations remained inaccurate after 6 ml of blood was discarded."}
{"id": "PMID:235116", "title": "Effect of low-frequency random noises on performance of a numeric monitoring task.", "content": "Previous findings indicate that continuous low-frequency noises at moderate sound-pressure levels do not produce decrements in vigilance performance. Such noises are commonly found in urban environments, however; and it is important to explore their effects carefully. This study employed 27 human males in a numeric monitoring task to evaluate the effects of low-frequency (11.5 to 350 Hz) noise at moderate sound-pressure levels (80 db). More numeric signals were missed during noise than during control runs. The effect was small but statistically reliable (P smaller than .033), in disagreement with previous research. The possible environmental impact of these findings is discussed.", "contents": "Effect of low-frequency random noises on performance of a numeric monitoring task. Previous findings indicate that continuous low-frequency noises at moderate sound-pressure levels do not produce decrements in vigilance performance. Such noises are commonly found in urban environments, however; and it is important to explore their effects carefully. This study employed 27 human males in a numeric monitoring task to evaluate the effects of low-frequency (11.5 to 350 Hz) noise at moderate sound-pressure levels (80 db). More numeric signals were missed during noise than during control runs. The effect was small but statistically reliable (P smaller than .033), in disagreement with previous research. The possible environmental impact of these findings is discussed."}
{"id": "PMID:235117", "title": "Unilateral brain lesions and MMPI performance: a preliminary study.", "content": "Samples of 15 Ss with right- and 20 Ss with left-hemisphere brain lesions secondary to war-related penetrating missile wounds were matched for age, education, and recency of injury and evaluated with the MMPI. Right-hemisphere lesioned Ss produced a composite profile with all scales within normal limits. In contrast, the composite profile of left-hemisphere lesioned Ss showed significant elevations on the Sc, D, and Hs clinical scales, suggesting increased psychopathological responses in such Ss. Although the general configurations of the composite MMPI profiles in the two samples were similar, significant differences in the elevation of both validity and clinical scales were obtained. The results tend to support previous findings of a depressive-catastrophic reaction in patients with lesions in the dominant hemisphere, while not supporting the euphoric-indifference response in nondominant-hemisphere lesioned Ss.", "contents": "Unilateral brain lesions and MMPI performance: a preliminary study. Samples of 15 Ss with right- and 20 Ss with left-hemisphere brain lesions secondary to war-related penetrating missile wounds were matched for age, education, and recency of injury and evaluated with the MMPI. Right-hemisphere lesioned Ss produced a composite profile with all scales within normal limits. In contrast, the composite profile of left-hemisphere lesioned Ss showed significant elevations on the Sc, D, and Hs clinical scales, suggesting increased psychopathological responses in such Ss. Although the general configurations of the composite MMPI profiles in the two samples were similar, significant differences in the elevation of both validity and clinical scales were obtained. The results tend to support previous findings of a depressive-catastrophic reaction in patients with lesions in the dominant hemisphere, while not supporting the euphoric-indifference response in nondominant-hemisphere lesioned Ss."}
{"id": "PMID:235124", "title": "Calcium role in depolarization-secretion coupling: an aequorin study in squid giant synapse.", "content": "Aequorin, a protein that emits light in the presence of calcium, was injected in the presynaptic terminal of the squid giant synapse. This injection was preceded by intracellular tetraethylammonium administration, which prolonged the duration of the presynaptic action potential. After this procedure light emission was evoked by single presynaptic spikes capable of releasing synaptic transmitter. In a second set of experiments, presynaptic tetraethylammonium injection was followed by the administration of tetrodotoxin extracellularly, which abolished the presynaptic action potential. Under these conditions artificial depolarization of the presynaptic terminal triggered the release of synaptic transmitter, in a graded manner. However, as previously reported by other authors, membrane potential steps to an internal positive value of approximately plus 90 mV (the suppression potential) produced a blockage of transmitter release for the duration of the imposed potential. Synaptic transmission recurred, nevertheless, as the current injection was terminated. A similar set of experiments, performed after the intracellular injection of aequorin in the presynaptic fiber, demonstrated that the aequorin light response was evoked by membrane potential steps capable of releasing synaptic transmitter. If the membrane potential was made positive to the \"suppression\" level, no light response was evoked but the light emission appeared, as did transmitter release, at the end of the current pulse. These experiments demonstrate that release of transmitter is directly correlated with intracellular calcium concentration and that the suppression potential is compatible with the existence of a calcium equilibrium potential at the presynaptic terminal.", "contents": "Calcium role in depolarization-secretion coupling: an aequorin study in squid giant synapse. Aequorin, a protein that emits light in the presence of calcium, was injected in the presynaptic terminal of the squid giant synapse. This injection was preceded by intracellular tetraethylammonium administration, which prolonged the duration of the presynaptic action potential. After this procedure light emission was evoked by single presynaptic spikes capable of releasing synaptic transmitter. In a second set of experiments, presynaptic tetraethylammonium injection was followed by the administration of tetrodotoxin extracellularly, which abolished the presynaptic action potential. Under these conditions artificial depolarization of the presynaptic terminal triggered the release of synaptic transmitter, in a graded manner. However, as previously reported by other authors, membrane potential steps to an internal positive value of approximately plus 90 mV (the suppression potential) produced a blockage of transmitter release for the duration of the imposed potential. Synaptic transmission recurred, nevertheless, as the current injection was terminated. A similar set of experiments, performed after the intracellular injection of aequorin in the presynaptic fiber, demonstrated that the aequorin light response was evoked by membrane potential steps capable of releasing synaptic transmitter. If the membrane potential was made positive to the \"suppression\" level, no light response was evoked but the light emission appeared, as did transmitter release, at the end of the current pulse. These experiments demonstrate that release of transmitter is directly correlated with intracellular calcium concentration and that the suppression potential is compatible with the existence of a calcium equilibrium potential at the presynaptic terminal."}
{"id": "PMID:235125", "title": "Evidence for adenosine diphosphate ribosylation of Ca2+, Mg2+-dependent endonuclease.", "content": "The molecular basis for the inhibition of the Ca2+,Mg2+-dependent endonuclease resulting from the formation of poly(adenosine diphosphate ribose) (ADP-Rib) was studies in a simplified system containing purified rat liver or bull semen endonuclease, purified rat liver poly(ADP-Rib) synthetase, [3H]NAD+, and DNA. Poly-(adp-rib) synthetase activity was stimulated when Ca2+, Mg2+-dependent endonuclease was added to the reaction mixture in place of histones, suggesting that the endonuclease can act as an acceptor for ADP-Rib. Evidence was presented to show that the ADP-Rib moiety of [3H]NAD+ was incorporated in the endonuclease fraction. The [3H]ADP-Rib bound to the endonuclease was in the form of monomers and oligomers and not long chain polymers. The present results suggest that the Ca2+,Mg2+-dependent endonuclease was ADP-ribosylated when the endonuclease was incubated with poly(ADP-Rib) synthetase and NAD+.", "contents": "Evidence for adenosine diphosphate ribosylation of Ca2+, Mg2+-dependent endonuclease. The molecular basis for the inhibition of the Ca2+,Mg2+-dependent endonuclease resulting from the formation of poly(adenosine diphosphate ribose) (ADP-Rib) was studies in a simplified system containing purified rat liver or bull semen endonuclease, purified rat liver poly(ADP-Rib) synthetase, [3H]NAD+, and DNA. Poly-(adp-rib) synthetase activity was stimulated when Ca2+, Mg2+-dependent endonuclease was added to the reaction mixture in place of histones, suggesting that the endonuclease can act as an acceptor for ADP-Rib. Evidence was presented to show that the ADP-Rib moiety of [3H]NAD+ was incorporated in the endonuclease fraction. The [3H]ADP-Rib bound to the endonuclease was in the form of monomers and oligomers and not long chain polymers. The present results suggest that the Ca2+,Mg2+-dependent endonuclease was ADP-ribosylated when the endonuclease was incubated with poly(ADP-Rib) synthetase and NAD+."}
{"id": "PMID:235126", "title": "Breaking of seed dormancy by catalase inhibition.", "content": "Germination of some dormant seeds is promoted by solutions of thiourea, sodium nitrite, and hydroxylamine salts. The promotions are accompanied by irreversible inhibition of catalase (EC 1.11.1.6) in extracts from the seeds. The seeds are also promoted in germination by catechol and pyrogallol solutions. These effects are recorded for lettuce (Lactuca sativa L. cv. Grand Rapids) and pigweed (Amaranthus albus L.) seeds. The results indicae that metabolically derived hydrogen peroxide, spared from decomposition by catalase inhibition, oxidizes reduced NADPH required as the oxidant in the pentose pathway of glucose use. The metabolic system for such use of H2O2 involves the enzymes, peroxidase (EC 1.11.1.7) and pyridine nucleotide quinone oxidoreductase (EC 1.6.99.2), which are present in the dormant seed prior to imbibition of water.", "contents": "Breaking of seed dormancy by catalase inhibition. Germination of some dormant seeds is promoted by solutions of thiourea, sodium nitrite, and hydroxylamine salts. The promotions are accompanied by irreversible inhibition of catalase (EC 1.11.1.6) in extracts from the seeds. The seeds are also promoted in germination by catechol and pyrogallol solutions. These effects are recorded for lettuce (Lactuca sativa L. cv. Grand Rapids) and pigweed (Amaranthus albus L.) seeds. The results indicae that metabolically derived hydrogen peroxide, spared from decomposition by catalase inhibition, oxidizes reduced NADPH required as the oxidant in the pentose pathway of glucose use. The metabolic system for such use of H2O2 involves the enzymes, peroxidase (EC 1.11.1.7) and pyridine nucleotide quinone oxidoreductase (EC 1.6.99.2), which are present in the dormant seed prior to imbibition of water."}
{"id": "PMID:235127", "title": "A kinetic study in vitro of the reoxidation of interchain disulfide bonds in a human immunoglobulin IgGLk. Correlation between sulfhydryl disappearance and intermediates in covalent assembly of H2L2.", "content": "After reduction by dithiothreitol and removal of the reductant by molecular sieve chromatography, the four interchain disulfide bonds of the human IgGlk protein Fro reoxidize in the presence of oxygen and trace metal ions. The six molecular components of the reoxidation--L (light chain), H (heavy chain), HL, H2, H2L, H2L2--are quantitatively determined from polyacrylamide gels containing sodium dodecyl sulfate and the time-dependent sulfhydryl titer is measured with 5,5'-dithiobis-(2-nitrobenzoic acid). The rates of H2L2 covalent assembly depend on pH in an unexpected way: If the reduced protein is chromatographed at pH 3.2 and then adjusted to pH 7.5 (25 degrees, ionic strength equals 0.14), H2L2 formation proceeds rapidly, with half-times ranging between 20 and 40 min. In contrast, if chromatography is carried out at pH 5.5 before adjusting to the same final conditions, the half-times for H2L2 formation are considerably longer (120-180 min). The half-times in the former case approach the somewhat faster rates of H2L2 assembly observed in pulse-chase experiments with various types of mouse, IgG-producing cells [Baumal, et al. (1971) J. Exp. Med. 134, 1316-1334]. To facilitate comparison of experiments and models, we plot the concentrations of the six components against the corresponding number of sulfhydryl equivalents per mole of Fro. The respective plots for the pH 3.2 leads to 7.5 and 5.5 leads to 7.5 experiments are very similar despite the rate differences. Moreover, these plots differ significantly from the calculated plot for a hypothetical random reoxidation in which the intrinsic probability for formation of each correct HL and H2 disulfide bond is assumed equal and independent. It is concluded that the in vitro reoxidation of Fro (i) is other than random; (ii) involved a pathway of pathways with HL, H2, and H2L precursors; and (iii) involves at least some kinetic cooperativity in bond formation, since no model bases solely on independent bond formation adequately accounts for the results. The models were used also to examine the cellular assembly pathways of mouse IgG proteins.", "contents": "A kinetic study in vitro of the reoxidation of interchain disulfide bonds in a human immunoglobulin IgGLk. Correlation between sulfhydryl disappearance and intermediates in covalent assembly of H2L2. After reduction by dithiothreitol and removal of the reductant by molecular sieve chromatography, the four interchain disulfide bonds of the human IgGlk protein Fro reoxidize in the presence of oxygen and trace metal ions. The six molecular components of the reoxidation--L (light chain), H (heavy chain), HL, H2, H2L, H2L2--are quantitatively determined from polyacrylamide gels containing sodium dodecyl sulfate and the time-dependent sulfhydryl titer is measured with 5,5'-dithiobis-(2-nitrobenzoic acid). The rates of H2L2 covalent assembly depend on pH in an unexpected way: If the reduced protein is chromatographed at pH 3.2 and then adjusted to pH 7.5 (25 degrees, ionic strength equals 0.14), H2L2 formation proceeds rapidly, with half-times ranging between 20 and 40 min. In contrast, if chromatography is carried out at pH 5.5 before adjusting to the same final conditions, the half-times for H2L2 formation are considerably longer (120-180 min). The half-times in the former case approach the somewhat faster rates of H2L2 assembly observed in pulse-chase experiments with various types of mouse, IgG-producing cells [Baumal, et al. (1971) J. Exp. Med. 134, 1316-1334]. To facilitate comparison of experiments and models, we plot the concentrations of the six components against the corresponding number of sulfhydryl equivalents per mole of Fro. The respective plots for the pH 3.2 leads to 7.5 and 5.5 leads to 7.5 experiments are very similar despite the rate differences. Moreover, these plots differ significantly from the calculated plot for a hypothetical random reoxidation in which the intrinsic probability for formation of each correct HL and H2 disulfide bond is assumed equal and independent. It is concluded that the in vitro reoxidation of Fro (i) is other than random; (ii) involved a pathway of pathways with HL, H2, and H2L precursors; and (iii) involves at least some kinetic cooperativity in bond formation, since no model bases solely on independent bond formation adequately accounts for the results. The models were used also to examine the cellular assembly pathways of mouse IgG proteins."}
{"id": "PMID:235144", "title": "Effects of maintenance amitriptyline and psychotherapy on symptoms of depression.", "content": "Depressives responding to initial treatment were maintained on amitriptyline for eight months, withdrawn double-blind to placebo after two months, or withdrawn overtly onto no medication. In each group half the patients received weekly psychotherapy and half were seen once monthly. Effects on symptom ratings were examined. Maintenance amitriptyline gave a significant advantage over early withdrawal in preventing symptom recrudescence. There were no differences between double-blind or overt withdrawal. There were no interactions between drug withdrawal and psychotherapy. Psychotherapy produced no significant advantages over low contact on symptoms, although it did improve social adjustment ratings reported elsewhere.", "contents": "Effects of maintenance amitriptyline and psychotherapy on symptoms of depression. Depressives responding to initial treatment were maintained on amitriptyline for eight months, withdrawn double-blind to placebo after two months, or withdrawn overtly onto no medication. In each group half the patients received weekly psychotherapy and half were seen once monthly. Effects on symptom ratings were examined. Maintenance amitriptyline gave a significant advantage over early withdrawal in preventing symptom recrudescence. There were no differences between double-blind or overt withdrawal. There were no interactions between drug withdrawal and psychotherapy. Psychotherapy produced no significant advantages over low contact on symptoms, although it did improve social adjustment ratings reported elsewhere."}
{"id": "PMID:235148", "title": "The temporal and pathological significance of perfusion failure following renal transplantation.", "content": "Serial dynamic studies with 99mTc-DTPA are a useful method of monitoring renal transplants. Radionuclide images obtained within 24 hours after surgery and at regular intervals thereafter can identify pathological conditions. The decline or absence of perfusion, coupled with the elapsed time following surgery, can be used to differentiate vascular occlusion or hyperacute rejection from acute rejection, acute tubular necrosis, or accelerated or chronic rejection. 99mTc-pyrophosphate can be used to simultaneously evaluate transplant function and locate possible aseptic necrosis of bone. Both studies are noninvasive and have been performed safely on numerous occasions over a period of several years.", "contents": "The temporal and pathological significance of perfusion failure following renal transplantation. Serial dynamic studies with 99mTc-DTPA are a useful method of monitoring renal transplants. Radionuclide images obtained within 24 hours after surgery and at regular intervals thereafter can identify pathological conditions. The decline or absence of perfusion, coupled with the elapsed time following surgery, can be used to differentiate vascular occlusion or hyperacute rejection from acute rejection, acute tubular necrosis, or accelerated or chronic rejection. 99mTc-pyrophosphate can be used to simultaneously evaluate transplant function and locate possible aseptic necrosis of bone. Both studies are noninvasive and have been performed safely on numerous occasions over a period of several years."}
{"id": "PMID:235149", "title": "Patterns of excretion of radioactive chelates in obstructive uropathy.", "content": "Radioactive chelates such as 99mTc-DTPA are advantageous in ranal imaging, particularly in defining functional and morphological abnormalities of the excretory tract. In a review of more than 200 studies, 19 cases of lower-tract disease were diagnosed by the gamma camera image alone. In 16 of them, the diagnosis was confirmed by excretory urography. Normal radionuclide patterns are described and compared with the characteristic findings in caliectasis, hydronephrosis, and hydroureter. By facilitating evaluation of renal perfusion, renal glomerular function, and gross renal structure as well as good difinition of excretory function, radioactive chelate imaging is ideally suited for use as general screening test.", "contents": "Patterns of excretion of radioactive chelates in obstructive uropathy. Radioactive chelates such as 99mTc-DTPA are advantageous in ranal imaging, particularly in defining functional and morphological abnormalities of the excretory tract. In a review of more than 200 studies, 19 cases of lower-tract disease were diagnosed by the gamma camera image alone. In 16 of them, the diagnosis was confirmed by excretory urography. Normal radionuclide patterns are described and compared with the characteristic findings in caliectasis, hydronephrosis, and hydroureter. By facilitating evaluation of renal perfusion, renal glomerular function, and gross renal structure as well as good difinition of excretory function, radioactive chelate imaging is ideally suited for use as general screening test."}
{"id": "PMID:235151", "title": "Pulmonary function studies and oxygen transfer in patients with liver cirrhosis and different degree of portasystemic encephalopathy.", "content": "Pulmonary function and oxygen transfer was studied in five patients with cirrhosis of the liver and different degrees of portasystemic encephalopathy. Four patients were restudied after a change in CNS function. The contribution of various parameters of pulmonary gas exchange to the unsaturation found was evaluated employing the graphic analysis described by King and Briscoe. The following results were obtained: (1) there was no inequality of ventilation as judged by a nitrogen washout study; (2) a large true venous admixture was found in all patients; (3) in four patients studied twice venous admixture was larger when mean EEG frequency was lower; (4) besides the true venous admixture a low overall D/Q ratio was an important factor contributing to unsaturation in most cases; (5) in some cases a decreased overall V/Q ratio contributed to the unsaturation. This decreased V/Q ratio appeared to be due to an increase in pulmonary perfusion without a concomitant rise in ventilation. Changes in pulmonary perfusion pathways are suggested as the most likely cause of the defect in oxygen transfer found in patients with cirrhosis.", "contents": "Pulmonary function studies and oxygen transfer in patients with liver cirrhosis and different degree of portasystemic encephalopathy. Pulmonary function and oxygen transfer was studied in five patients with cirrhosis of the liver and different degrees of portasystemic encephalopathy. Four patients were restudied after a change in CNS function. The contribution of various parameters of pulmonary gas exchange to the unsaturation found was evaluated employing the graphic analysis described by King and Briscoe. The following results were obtained: (1) there was no inequality of ventilation as judged by a nitrogen washout study; (2) a large true venous admixture was found in all patients; (3) in four patients studied twice venous admixture was larger when mean EEG frequency was lower; (4) besides the true venous admixture a low overall D/Q ratio was an important factor contributing to unsaturation in most cases; (5) in some cases a decreased overall V/Q ratio contributed to the unsaturation. This decreased V/Q ratio appeared to be due to an increase in pulmonary perfusion without a concomitant rise in ventilation. Changes in pulmonary perfusion pathways are suggested as the most likely cause of the defect in oxygen transfer found in patients with cirrhosis."}
{"id": "PMID:235152", "title": "[Effects of drugs and environmental factors on ciliary movement (author's transl)].", "content": "The effects of a number of drugs, potassium and calcium ions, and air humidity on mucociliary function were studied in isolated preparations of rats bronchial tree. Adrenergic drugs increased the rate of ciliary beat significantly. Cilioexitation also occurred, though to a smaller degree, after application of acetylcholine, pilocarpine, aminophylline, prednisolone, KI and NH4C1. Serotonin, histamine, and acetylcystein did not change ciliary frequency to any significant degree; however, histamine in high concentrations caused ciliary incoordination. Codein and normetadon, nicotine and pentobarbital had a dose-dependent ciliodepressive effect. However, small concentrations of nicotine and pentobarbital were slightly stimulative. Methysergid and phentolamine were slightly ciliodepressive. Alterations of the concentrations of calcium and potassium ions in the nutritive solution influenced ciliary frequency but had no effect on other characteristic features of the ciliary movement. The ciliated epithelium of the bronchial tree could be irreversibly damaged by air having low relative humidity.", "contents": "[Effects of drugs and environmental factors on ciliary movement (author's transl)]. The effects of a number of drugs, potassium and calcium ions, and air humidity on mucociliary function were studied in isolated preparations of rats bronchial tree. Adrenergic drugs increased the rate of ciliary beat significantly. Cilioexitation also occurred, though to a smaller degree, after application of acetylcholine, pilocarpine, aminophylline, prednisolone, KI and NH4C1. Serotonin, histamine, and acetylcystein did not change ciliary frequency to any significant degree; however, histamine in high concentrations caused ciliary incoordination. Codein and normetadon, nicotine and pentobarbital had a dose-dependent ciliodepressive effect. However, small concentrations of nicotine and pentobarbital were slightly stimulative. Methysergid and phentolamine were slightly ciliodepressive. Alterations of the concentrations of calcium and potassium ions in the nutritive solution influenced ciliary frequency but had no effect on other characteristic features of the ciliary movement. The ciliated epithelium of the bronchial tree could be irreversibly damaged by air having low relative humidity."}
{"id": "PMID:235153", "title": "Deleterious effects of hyperbaric oxygen treatment on mortality and pathological changes in nitrogen-dioxide-poisoned dogs.", "content": "Nitrogen dioxide poisoning was experimentally produced in dogs. PO2, PCO2 and pH were measured in poisoned animals and during treatment with hyperbaric oxygen (OHP) lung lesions in both groups were evaluated. It is concluded that OHP has a deleterious effect both in terms of mortality and pathological changes.", "contents": "Deleterious effects of hyperbaric oxygen treatment on mortality and pathological changes in nitrogen-dioxide-poisoned dogs. Nitrogen dioxide poisoning was experimentally produced in dogs. PO2, PCO2 and pH were measured in poisoned animals and during treatment with hyperbaric oxygen (OHP) lung lesions in both groups were evaluated. It is concluded that OHP has a deleterious effect both in terms of mortality and pathological changes."}
{"id": "PMID:235156", "title": "Interaction between local anesthetics and analeptic drugs.", "content": "Although clinicall undesirable, the fortuitous pharmacologic interactions between local anesthetic agents and analeptic drugs may be protective when large doses of both agents are used. Mice pretreated with procaine, lidocaine, and tetracaine had a lower incidence of seizures when convulsive doses of either nikethamide or doxapram hydrochloride were given intraperitoneally. Mortality was also decreased in the groups given nikethamide and was zero in the animals treated with doxapram. All animals treated with pentylenetetrazol convulsed and only lidocaine (also used as an anticonvulsant) was able to reduce mortality in this group. Of the local anesthetic agents, tetracaine afforded the least protection from death, whereas lidocaine seemed to be most effective.", "contents": "Interaction between local anesthetics and analeptic drugs. Although clinicall undesirable, the fortuitous pharmacologic interactions between local anesthetic agents and analeptic drugs may be protective when large doses of both agents are used. Mice pretreated with procaine, lidocaine, and tetracaine had a lower incidence of seizures when convulsive doses of either nikethamide or doxapram hydrochloride were given intraperitoneally. Mortality was also decreased in the groups given nikethamide and was zero in the animals treated with doxapram. All animals treated with pentylenetetrazol convulsed and only lidocaine (also used as an anticonvulsant) was able to reduce mortality in this group. Of the local anesthetic agents, tetracaine afforded the least protection from death, whereas lidocaine seemed to be most effective."}
{"id": "PMID:235157", "title": "Vascular spider: a cutaneous manifestation of hyperdynamic blood flow in hepatic cirrhosis.", "content": "Arteriography and gas analysis of blood aspirated from a vascular spider in a patient with hepatic cirrhosis were done before excision and histologic examination of the lesion. This study supports earlier work suggesting that a spider angioma is a cutaneous manifestation of a generalized hyperdynamic circulation in hepatic cirrhosis. Moreover, based upon a variety of experimental and clinical observations on the splanchnic circulation in cirrhosis, it is suggested that the portal hypertension blood flow encounters the obstacle posed by the scarred liver (\"active congestion\").", "contents": "Vascular spider: a cutaneous manifestation of hyperdynamic blood flow in hepatic cirrhosis. Arteriography and gas analysis of blood aspirated from a vascular spider in a patient with hepatic cirrhosis were done before excision and histologic examination of the lesion. This study supports earlier work suggesting that a spider angioma is a cutaneous manifestation of a generalized hyperdynamic circulation in hepatic cirrhosis. Moreover, based upon a variety of experimental and clinical observations on the splanchnic circulation in cirrhosis, it is suggested that the portal hypertension blood flow encounters the obstacle posed by the scarred liver (\"active congestion\")."}
{"id": "PMID:235158", "title": "Fatal paralytic ileus complicating phenothiazine therapy.", "content": "The occurrence of fatal paralytic ileus with peritonitis in a patient receiving phenothiazines and an antiparkinsonian agent is described. Although sporadic reports of this complication have appeared, it has not been emphasized in the literature. Only by being alert to this problem can one hope to achieve earlier diagnosis and begin prompt and appropriate treatment.", "contents": "Fatal paralytic ileus complicating phenothiazine therapy. The occurrence of fatal paralytic ileus with peritonitis in a patient receiving phenothiazines and an antiparkinsonian agent is described. Although sporadic reports of this complication have appeared, it has not been emphasized in the literature. Only by being alert to this problem can one hope to achieve earlier diagnosis and begin prompt and appropriate treatment."}
{"id": "PMID:235161", "title": "Cytotoxic macrophage in graft-versus-host reaction.", "content": "Peritoneal macrophages of F1 hybrid mice injected with parental strain spleen cells 8-14 days previously (\"early\" graft-versus-host (GVH) macrophages) develop an increased ability to destroy in vitro bystanding target cells of syngeneic, allogeneic, and xenogeneic origin. At later stages of GVH reaction, the nonspecific cytotoxicity of macrophages wanes (\"late\" GVH macrophages) and does not differ much from that of control macrophages. Trypsinization of early GVH macrophages or iodoacetate treatment significantly reduces their cytotoxicity, whereas anti-theta serum and complement have only a moderate effect. Antimouse IgM antibody significantly enhanced the cytotoxic potential of early GVH macrophages, but had no effect either on normal or late GVH macrophages. In contrast, antimouse IgG antibody enhanced, although slightly, only the cytotoxic activity of late GVH macrophages. Two possible explanations of the increased cytotoxicity of early GVH macrophages are offered: (1) cytophilic antibody of IgM type, directed against host antigens, renders macrophages capable of damaging nonspecifically bystanding target cells upon contact with antigen; (2) IgM alloantibody produced by parental cells changes the surface properties of macrophages and contributes to the cytotoxicity of these cells.", "contents": "Cytotoxic macrophage in graft-versus-host reaction. Peritoneal macrophages of F1 hybrid mice injected with parental strain spleen cells 8-14 days previously (\"early\" graft-versus-host (GVH) macrophages) develop an increased ability to destroy in vitro bystanding target cells of syngeneic, allogeneic, and xenogeneic origin. At later stages of GVH reaction, the nonspecific cytotoxicity of macrophages wanes (\"late\" GVH macrophages) and does not differ much from that of control macrophages. Trypsinization of early GVH macrophages or iodoacetate treatment significantly reduces their cytotoxicity, whereas anti-theta serum and complement have only a moderate effect. Antimouse IgM antibody significantly enhanced the cytotoxic potential of early GVH macrophages, but had no effect either on normal or late GVH macrophages. In contrast, antimouse IgG antibody enhanced, although slightly, only the cytotoxic activity of late GVH macrophages. Two possible explanations of the increased cytotoxicity of early GVH macrophages are offered: (1) cytophilic antibody of IgM type, directed against host antigens, renders macrophages capable of damaging nonspecifically bystanding target cells upon contact with antigen; (2) IgM alloantibody produced by parental cells changes the surface properties of macrophages and contributes to the cytotoxicity of these cells."}
{"id": "PMID:235162", "title": "Inhibition of the graft-versus-host reaction. III. Altered in vivo distribution of spleen cells pretreated with Fab fragments of antithymocyte globulin.", "content": "51Cr-labeled parental strain spleen cells were pretreated in vitro with antithymocyte globulin (ATG) or Fab fragments of ATG before i.v. injection into F1 recipients. Recipients were killed at various intervals after injection and their organs were assayed for radioactivity in order to determine the in vivo distribution pattern of pretreated cells. 51Cr spleen cells pretreated with ATG were almost totally prevented from migrating to spleens, lymph nodes, bone marrow, Peyer's patches, lungs, and peripheral blood of recipients. Pretreatment of 51Cr spleen cells with noncytotoxic Fab of ATG also inhibited localization to these organs and tissues; however, the inhibition was not as complete as that of ATG-treated cells. Localization of Fab-treated 51Cr spleen cells to recipient nodes was inhibited to a greater extent than was localization to recipient spleens. There was no significant difference in the extent of inhibition of ATG-treated 51Cr spleen cells to recipient nodes and spleen. Organ counts from recipients killed at various intervals after injection of Fab-treated 51Cr spleen cells showed that Fab-treated cells do not recover their recirculating potential in vivo.", "contents": "Inhibition of the graft-versus-host reaction. III. Altered in vivo distribution of spleen cells pretreated with Fab fragments of antithymocyte globulin. 51Cr-labeled parental strain spleen cells were pretreated in vitro with antithymocyte globulin (ATG) or Fab fragments of ATG before i.v. injection into F1 recipients. Recipients were killed at various intervals after injection and their organs were assayed for radioactivity in order to determine the in vivo distribution pattern of pretreated cells. 51Cr spleen cells pretreated with ATG were almost totally prevented from migrating to spleens, lymph nodes, bone marrow, Peyer's patches, lungs, and peripheral blood of recipients. Pretreatment of 51Cr spleen cells with noncytotoxic Fab of ATG also inhibited localization to these organs and tissues; however, the inhibition was not as complete as that of ATG-treated cells. Localization of Fab-treated 51Cr spleen cells to recipient nodes was inhibited to a greater extent than was localization to recipient spleens. There was no significant difference in the extent of inhibition of ATG-treated 51Cr spleen cells to recipient nodes and spleen. Organ counts from recipients killed at various intervals after injection of Fab-treated 51Cr spleen cells showed that Fab-treated cells do not recover their recirculating potential in vivo."}
{"id": "PMID:235163", "title": "Specific unresponsiveness to skin allografts in mice. IV. Immunological reactivity of mice treated with liver extracts, Bordetella pertussis, and antilymphocyte serum.", "content": "The strain-specific unresponsiveness to H-2 incompatible skin allografts induced by treatment of adult mice with single inoculations of donor strain liver extract and Bordetella pertussis vaccine, as well as three doses of antilymphocyte serum, has been investigated by several in vivo and in vitro methods, with a view to elucidating it mechanism. Lymphoid cells from mice with long surviving skin grafts were found to be reactive in graft-versus-host assays (as measured by splenomegaly or popliteal lymph node enlargement), and mixed lymphocyte culture tests gave positive results. Attempts to cause lethal runting of F1 hybrid mice injected at birth with spleen cells from unresponsive mice gave variable results. However, the injection of F1 hybrid cells into the footpads of unresponsive animals failed to elicit a significant host-versus-graft response. Although lymphoid cells from unresponsive animals did not include detectable numbers of cytotoxic cells, such cells could be generated by previous in vitro mixed lymphocyte culture stimulation or, to some degree, by the injection of the animals with F1 hybrid cells. Attempts to prevent mixed lymphocyte culture stimulation or cytotoxicity with serum from unresponsive mice failed at the serum concentrations used. The data indicate that long-term unresponsiveness in this system is maintained by the production in the hosts of factors that interfere with the cell-mediated response.", "contents": "Specific unresponsiveness to skin allografts in mice. IV. Immunological reactivity of mice treated with liver extracts, Bordetella pertussis, and antilymphocyte serum. The strain-specific unresponsiveness to H-2 incompatible skin allografts induced by treatment of adult mice with single inoculations of donor strain liver extract and Bordetella pertussis vaccine, as well as three doses of antilymphocyte serum, has been investigated by several in vivo and in vitro methods, with a view to elucidating it mechanism. Lymphoid cells from mice with long surviving skin grafts were found to be reactive in graft-versus-host assays (as measured by splenomegaly or popliteal lymph node enlargement), and mixed lymphocyte culture tests gave positive results. Attempts to cause lethal runting of F1 hybrid mice injected at birth with spleen cells from unresponsive mice gave variable results. However, the injection of F1 hybrid cells into the footpads of unresponsive animals failed to elicit a significant host-versus-graft response. Although lymphoid cells from unresponsive animals did not include detectable numbers of cytotoxic cells, such cells could be generated by previous in vitro mixed lymphocyte culture stimulation or, to some degree, by the injection of the animals with F1 hybrid cells. Attempts to prevent mixed lymphocyte culture stimulation or cytotoxicity with serum from unresponsive mice failed at the serum concentrations used. The data indicate that long-term unresponsiveness in this system is maintained by the production in the hosts of factors that interfere with the cell-mediated response."}
{"id": "PMID:235165", "title": "[Corticosteroid hormones and histones (on the mechanism of action of hormones)].", "content": "The role of interaction between corticosteroid hormones and histones is considered with regard to hormonal activation of genes and some secondary changes of cells functional condition due to the presence of the hormones.", "contents": "[Corticosteroid hormones and histones (on the mechanism of action of hormones)]. The role of interaction between corticosteroid hormones and histones is considered with regard to hormonal activation of genes and some secondary changes of cells functional condition due to the presence of the hormones."}
{"id": "PMID:235167", "title": "Early orchiopexy and testis tumors.", "content": "A testicular tumor developed in a twenty-year-old man who had undergone orchiopexy at age six. The case illustrates that early orchiopexy affords no protection against subsequent malignant degeneration. The importance of an inguinal approach and a high orchiectomy are stressed.", "contents": "Early orchiopexy and testis tumors. A testicular tumor developed in a twenty-year-old man who had undergone orchiopexy at age six. The case illustrates that early orchiopexy affords no protection against subsequent malignant degeneration. The importance of an inguinal approach and a high orchiectomy are stressed."}
{"id": "PMID:235168", "title": "[Nature of metabolic alkalosis in the postoperative period in patients with pulmonary tuberculosis].", "content": "Sixty five patients with pulmonary tuberculosis subjected to extensive and traumatic surgical interventions were investigated. Metabolic alkalosis to the end of the 1st--2d postoperative day would develop in patients, who showed acid-base balance disorders toward acid aspect during the operation. In the mechanism of development of a grave decompensated postoperative metabolic alkalosis the role of a trigger factor is played by a massive intraoperative blood loss with marked hemodynamic disturbances in the immediate postoperative period.", "contents": "[Nature of metabolic alkalosis in the postoperative period in patients with pulmonary tuberculosis]. Sixty five patients with pulmonary tuberculosis subjected to extensive and traumatic surgical interventions were investigated. Metabolic alkalosis to the end of the 1st--2d postoperative day would develop in patients, who showed acid-base balance disorders toward acid aspect during the operation. In the mechanism of development of a grave decompensated postoperative metabolic alkalosis the role of a trigger factor is played by a massive intraoperative blood loss with marked hemodynamic disturbances in the immediate postoperative period."}
{"id": "PMID:235170", "title": "Investigation into diagnosis and treatment of cobalt deficiency in lambs.", "content": "The development of cobalt deficiency was studied in 30 Scottish Blackface lambs grazing pasture on a soil containing 0-17 ppm cobalt. By the end of an eight-week period 50 per cent of lambs were subjectively appraised as showing signs of cobalt deficiency. After a further period lasting four weeks, during which three groups of lambs were studied (one group, least affected by cobalt deficiency, acted as control, the second received a single cobalt bullet and the third received oral doses of 200 mg cobalt chloride at the beginning of the period and three weeks later). Mean urinary formiminoglutamic acid (FIGLU) concentrations were inversely related to serum vitamin B12 concentrations and increased from 0-08 to 0-20 mumole per ml in group 1, and decreased to virtually zero within one week of treatment in groups 2 and 3. The use of serum vitamin B12 and urinary FIGLU concentrations in the diagnosis of cobalt deficiency in sheep are discussed.", "contents": "Investigation into diagnosis and treatment of cobalt deficiency in lambs. The development of cobalt deficiency was studied in 30 Scottish Blackface lambs grazing pasture on a soil containing 0-17 ppm cobalt. By the end of an eight-week period 50 per cent of lambs were subjectively appraised as showing signs of cobalt deficiency. After a further period lasting four weeks, during which three groups of lambs were studied (one group, least affected by cobalt deficiency, acted as control, the second received a single cobalt bullet and the third received oral doses of 200 mg cobalt chloride at the beginning of the period and three weeks later). Mean urinary formiminoglutamic acid (FIGLU) concentrations were inversely related to serum vitamin B12 concentrations and increased from 0-08 to 0-20 mumole per ml in group 1, and decreased to virtually zero within one week of treatment in groups 2 and 3. The use of serum vitamin B12 and urinary FIGLU concentrations in the diagnosis of cobalt deficiency in sheep are discussed."}
{"id": "PMID:235171", "title": "Differences in the incorporation of L- and DL-Amino acids into renal tubular cells.  An autoradiographic study.", "content": "The cytoplasmic uptake of 3H-L-leucine and 3H-L-proline by hepatocytes and cells of the proximal and distal convoluted and of the collecting tubules of the kidney was compared with that of 3H-DL-leucine and 3H-DL-proline in an autoradiographic study.  34 male white Sprague-Dawley rats were killed 1, 2, 6, and 24 hours after the intraperitoneal injection of these amino acids.  The rate of incorporation of 3H-L-leucine in the liver and in the renal tubules, as judged by the number of silver grains counted, was about twice that of 3H-L-proline.  In the tubules of the kidney the intensity of labelling progressively declined from the proximal convoluted to the collecting tubules.  When the two 3H-DL-amino acids were used, almost identical rates of incorporation were found in the liver as well as in the kidney.  The only exception was the pars recta of the proximal tubule: Here there could be found an unusually high uptake of 3H-DL-proline.  The values were not only higher than those found for the uptake of 3DL-leucine in this particular segment, but they also surpassed those due to 3H-DL-proline and 3DL-leucine in the other parts of the renal tubules, as well as in the liver.  The conspicuously high labelling seen in the pars recta after the injection of 3H-DL-proline suggests that there is present in the cells of this segment a d-amino acid oxidase, which may be relatively specific for D-proline.  The possibility is considered that this enzyme may participate in a detoxifying function of the pars recta.", "contents": "Differences in the incorporation of L- and DL-Amino acids into renal tubular cells.  An autoradiographic study. The cytoplasmic uptake of 3H-L-leucine and 3H-L-proline by hepatocytes and cells of the proximal and distal convoluted and of the collecting tubules of the kidney was compared with that of 3H-DL-leucine and 3H-DL-proline in an autoradiographic study.  34 male white Sprague-Dawley rats were killed 1, 2, 6, and 24 hours after the intraperitoneal injection of these amino acids.  The rate of incorporation of 3H-L-leucine in the liver and in the renal tubules, as judged by the number of silver grains counted, was about twice that of 3H-L-proline.  In the tubules of the kidney the intensity of labelling progressively declined from the proximal convoluted to the collecting tubules.  When the two 3H-DL-amino acids were used, almost identical rates of incorporation were found in the liver as well as in the kidney.  The only exception was the pars recta of the proximal tubule: Here there could be found an unusually high uptake of 3H-DL-proline.  The values were not only higher than those found for the uptake of 3DL-leucine in this particular segment, but they also surpassed those due to 3H-DL-proline and 3DL-leucine in the other parts of the renal tubules, as well as in the liver.  The conspicuously high labelling seen in the pars recta after the injection of 3H-DL-proline suggests that there is present in the cells of this segment a d-amino acid oxidase, which may be relatively specific for D-proline.  The possibility is considered that this enzyme may participate in a detoxifying function of the pars recta."}
{"id": "PMID:235172", "title": "[Factor XIII-heparin complex and its properties as a physiological solvent for unstabilized fibrin].", "content": "Some physiological properties of a complex of factor XIII with heparin were studied in relatively pure system in vitro. The complex was shown to exhibite the fibrinolytic activity toward unstabilized fibrin in the presence or absence of xi-aminocapronic acid, optimal pH for the activity was at pH 6.5--7.5 The activity was still observed after heating at 60 degrees C for 30 min. An excess of heparin was found to block the specific hydrolytic activity of the complex studied. The possibility of transition of heparin from a complex adrenaline-heparin to factor XIII with formation of factor XIII--heparin complex was shown. As a result of interaction of heparin with factor XIII the latter lost the fibrin-stabilizing activity.", "contents": "[Factor XIII-heparin complex and its properties as a physiological solvent for unstabilized fibrin]. Some physiological properties of a complex of factor XIII with heparin were studied in relatively pure system in vitro. The complex was shown to exhibite the fibrinolytic activity toward unstabilized fibrin in the presence or absence of xi-aminocapronic acid, optimal pH for the activity was at pH 6.5--7.5 The activity was still observed after heating at 60 degrees C for 30 min. An excess of heparin was found to block the specific hydrolytic activity of the complex studied. The possibility of transition of heparin from a complex adrenaline-heparin to factor XIII with formation of factor XIII--heparin complex was shown. As a result of interaction of heparin with factor XIII the latter lost the fibrin-stabilizing activity."}
{"id": "PMID:235173", "title": "[Effect of histamine on the hexokinase activity and RNA synthesis in the seminal vesicles and prostate of orchiectomized rats].", "content": "Due to orchidectomy, carried out two weeks before the experiment, in androgene-dependent rat tissues a hexokinase activity was found to be decreased several times. Within 24 hrs after administration of histamine into orchidectomized rats the hexokinase activity was increased by 96% in seminal follicles and by 160% in prostate. Incorporation of 3H-uridine into RNA of seminal follicles and prostate of castrated rat males was increased by 60% and 210%, respectively, within 3 hrs after the administration of histamine. The stimulating effects of histamine on RNA synthesis and the hexokinase activity were completely inhibited by actinomycin D. The data obtained suggest that histamine was one of mediators in the effect of testosterone on the tissues-targets.", "contents": "[Effect of histamine on the hexokinase activity and RNA synthesis in the seminal vesicles and prostate of orchiectomized rats]. Due to orchidectomy, carried out two weeks before the experiment, in androgene-dependent rat tissues a hexokinase activity was found to be decreased several times. Within 24 hrs after administration of histamine into orchidectomized rats the hexokinase activity was increased by 96% in seminal follicles and by 160% in prostate. Incorporation of 3H-uridine into RNA of seminal follicles and prostate of castrated rat males was increased by 60% and 210%, respectively, within 3 hrs after the administration of histamine. The stimulating effects of histamine on RNA synthesis and the hexokinase activity were completely inhibited by actinomycin D. The data obtained suggest that histamine was one of mediators in the effect of testosterone on the tissues-targets."}
{"id": "PMID:235174", "title": "[Change in the activity of NAD- and NADP-specific malate dehyrdogenases in oxygen deficiency in different tissues].", "content": "NAD-dependent malate dehydrogenase (1.1.1.37) activity was markedly decreased under hypoxia in rat brain and liver mitochondria and cytoplasm; most significant decrease was observed in brain cortex mitochondria. NADP-dependent malate dehydrogenase (1.1.1.40) activity was also reduced under these conditions and the most considerable changes were found in liver mitochondria and cytoplasm. Distribution of activities of these enzymes between subcellular fractions of brain and liver did not change under hypoxia. The oxaloacetate level rised by 20% in brain and decreased by 20-25% in liver under hypoxia.", "contents": "[Change in the activity of NAD- and NADP-specific malate dehyrdogenases in oxygen deficiency in different tissues]. NAD-dependent malate dehydrogenase (1.1.1.37) activity was markedly decreased under hypoxia in rat brain and liver mitochondria and cytoplasm; most significant decrease was observed in brain cortex mitochondria. NADP-dependent malate dehydrogenase (1.1.1.40) activity was also reduced under these conditions and the most considerable changes were found in liver mitochondria and cytoplasm. Distribution of activities of these enzymes between subcellular fractions of brain and liver did not change under hypoxia. The oxaloacetate level rised by 20% in brain and decreased by 20-25% in liver under hypoxia."}
{"id": "PMID:235176", "title": "[Microsome-associated 17beta-hydroxysteroid dehydrogenases of human placenta, ii kinetic studies and characterization of the solubilized estradiol-and testosterone-\"sensitive\" 17beta-HSD-Activities].", "content": "Detailed enzyme kinetic parameters of the reactions catalyzed by the two 17beta-hydroxysteroid dehydrogenases (17beta-HSD), which were solubilized from the microsomes of human placenta by treatment with phospholipase A, followed by enrichment and separation were determined. Both enzymes are strictly substrate specific. The most active substrate of one of the 17beta-HSD (fraction A) is estradiol-17beta, the other 17beta-HSD (fraction B) is sensitive to testosterone. Both NAD and NADP can serve as hydrogen transferring coenzymes, the latter giving about one-third of the initial rate of the former. With respect to the influence of temperature, different buffers and pH values, Michaelis constants (Km) with estradiol-17beta and testosterone as substrates, the solubilized and separated microsomal 17beta-HSD behave like those isolated from the cytoplasmic fraction. The two 17beta-HSD, after solubilization from the microsomal fraction of human placenta, enrichment and separation from each other, show only a little activity for the transfer of hydrogen between C17 of estradiol-17beta and C17 of androstenedione. On the other hand, intact microsomes and an integrated system prepared by recombination of the 17beta-enzymes by preincubation in phosphate buffer are able to catalyse very actively the transfer of hydrogen between estradiol-17beta and androstenedione. The effect of temperature and time on the recombination of the two enriched and separated microsomal enzyme activities and the determination of the pH-optimum of the hydrogen transfer reaction are described. Finally it is proposed that the hydrogen transfer between steroid hormones represents an aspect of the true reaction mechanism of steroid hormones: Steroid hormones function as hydrogen transferring coenzymes by forming part of a chain of hydrogen carriers.", "contents": "[Microsome-associated 17beta-hydroxysteroid dehydrogenases of human placenta, ii kinetic studies and characterization of the solubilized estradiol-and testosterone-\"sensitive\" 17beta-HSD-Activities]. Detailed enzyme kinetic parameters of the reactions catalyzed by the two 17beta-hydroxysteroid dehydrogenases (17beta-HSD), which were solubilized from the microsomes of human placenta by treatment with phospholipase A, followed by enrichment and separation were determined. Both enzymes are strictly substrate specific. The most active substrate of one of the 17beta-HSD (fraction A) is estradiol-17beta, the other 17beta-HSD (fraction B) is sensitive to testosterone. Both NAD and NADP can serve as hydrogen transferring coenzymes, the latter giving about one-third of the initial rate of the former. With respect to the influence of temperature, different buffers and pH values, Michaelis constants (Km) with estradiol-17beta and testosterone as substrates, the solubilized and separated microsomal 17beta-HSD behave like those isolated from the cytoplasmic fraction. The two 17beta-HSD, after solubilization from the microsomal fraction of human placenta, enrichment and separation from each other, show only a little activity for the transfer of hydrogen between C17 of estradiol-17beta and C17 of androstenedione. On the other hand, intact microsomes and an integrated system prepared by recombination of the 17beta-enzymes by preincubation in phosphate buffer are able to catalyse very actively the transfer of hydrogen between estradiol-17beta and androstenedione. The effect of temperature and time on the recombination of the two enriched and separated microsomal enzyme activities and the determination of the pH-optimum of the hydrogen transfer reaction are described. Finally it is proposed that the hydrogen transfer between steroid hormones represents an aspect of the true reaction mechanism of steroid hormones: Steroid hormones function as hydrogen transferring coenzymes by forming part of a chain of hydrogen carriers."}
{"id": "PMID:235177", "title": "Shuttles of artificial electron donors for photosystem I across the thylakoid membrane.", "content": "NADP+ reduction in isolated chloroplasts of spinach by photosystem I at the expense of various artificial donor systems is not inhibited by the plastoquinome antagonist dibromothymoquinone. The coupled ATP formation in such photoreductions is attributed to an artificial energy conserving site, i. e. a proton liberation during oxidation of the donor at the inner surface of the thylakoid membrane. Some donor systems for photosystem I are stimulated by uncouplers whereas others are not. The stimulation shows no correlation to the efficiency of the coupled photophosphorylation. Instead a correlation of the stimulation by uncouplers to the presence of an acidic OH-group in the donor molecule is seen. The uncoupler effect is therefore not explained by a release of electron transport control by the high energy state but rather by a pH-dependent distribution of the donor compound across the membrane. This is supported by the properties of donor systems in sonicated chloroplast particles with external oxidation sites of photosystem I.", "contents": "Shuttles of artificial electron donors for photosystem I across the thylakoid membrane. NADP+ reduction in isolated chloroplasts of spinach by photosystem I at the expense of various artificial donor systems is not inhibited by the plastoquinome antagonist dibromothymoquinone. The coupled ATP formation in such photoreductions is attributed to an artificial energy conserving site, i. e. a proton liberation during oxidation of the donor at the inner surface of the thylakoid membrane. Some donor systems for photosystem I are stimulated by uncouplers whereas others are not. The stimulation shows no correlation to the efficiency of the coupled photophosphorylation. Instead a correlation of the stimulation by uncouplers to the presence of an acidic OH-group in the donor molecule is seen. The uncoupler effect is therefore not explained by a release of electron transport control by the high energy state but rather by a pH-dependent distribution of the donor compound across the membrane. This is supported by the properties of donor systems in sonicated chloroplast particles with external oxidation sites of photosystem I."}
{"id": "PMID:235186", "title": "Assessment of GH releasing hormone activity in sephadex-separated fractions of porcine hypothalamic extracts by hypophyseal portal vessel infusion in the rat.", "content": "Growth hormone-releasing hormone (GH-RH) activity in Sephadex G-25 fractions of porcine stalk median eminence (SME) extracts was examined in vivo by infusing these samples into a rat hypophyseal portal vessel. The increment of immunoreactive GH levels in the serum was used as the index for GH-RH activity. The GH-RH activities were found in two different locations: in the early fractions Nos. 3-4, and in somewhat retarded fraction No. 7. These GH-RH activities were not due to TRH, vasopressin, or potassium. The location of LH releasing hormone (LH-RH) and prolactin release-inhibiting hormone (PR-IH) determined in this in vivo system was in agreement with those found in other in vivo and in vitro assay systems for LH-RH and PR-IH, respectively. These results help validate this assay system.", "contents": "Assessment of GH releasing hormone activity in sephadex-separated fractions of porcine hypothalamic extracts by hypophyseal portal vessel infusion in the rat. Growth hormone-releasing hormone (GH-RH) activity in Sephadex G-25 fractions of porcine stalk median eminence (SME) extracts was examined in vivo by infusing these samples into a rat hypophyseal portal vessel. The increment of immunoreactive GH levels in the serum was used as the index for GH-RH activity. The GH-RH activities were found in two different locations: in the early fractions Nos. 3-4, and in somewhat retarded fraction No. 7. These GH-RH activities were not due to TRH, vasopressin, or potassium. The location of LH releasing hormone (LH-RH) and prolactin release-inhibiting hormone (PR-IH) determined in this in vivo system was in agreement with those found in other in vivo and in vitro assay systems for LH-RH and PR-IH, respectively. These results help validate this assay system."}
{"id": "PMID:235189", "title": "Implications of phenothiazine side effects: a study of antiparkinsonian agents in an older population.", "content": "A study of anti-Parkinsonism agents in prolonged phenothiazine therapy seeks to clarify some anecdotal misconceptions. Antiparkinsonian agents do not appear to affect the therapeutic efficiency of phenothiazines, nor does using them on a \"demand\" basis increase the problems of control of parkinsonian side effects. Older patients, however, appear to require the extended usage of antiparkinsonian agents rather more than some studies would suggest. Sustained release antiparkinsonian agents may yet further simplify the management of schizophrenia.", "contents": "Implications of phenothiazine side effects: a study of antiparkinsonian agents in an older population. A study of anti-Parkinsonism agents in prolonged phenothiazine therapy seeks to clarify some anecdotal misconceptions. Antiparkinsonian agents do not appear to affect the therapeutic efficiency of phenothiazines, nor does using them on a \"demand\" basis increase the problems of control of parkinsonian side effects. Older patients, however, appear to require the extended usage of antiparkinsonian agents rather more than some studies would suggest. Sustained release antiparkinsonian agents may yet further simplify the management of schizophrenia."}
{"id": "PMID:235190", "title": "Changes in lysosomes during ageing of parenchymal and nonparenchymal liver cells.", "content": "Intact and viable parenchymal and non-parenchymal liver cell preparations were isolated by enzyme perfusion techniques from young and old rats. The distribution of the lysosomal enzymes acid phosphatase, beta-galactosidase, cathepsin D, acid DNAse, and arylsulphatase B over parenchymal and non-parenchymal cells was determined. In addition, morphological and morphometric changes which occur in parenchymal cells with age were investigated. All lysosomal enzymes studied are present in both cell classes, but non-parenchymal cells possess much ligher activities per mg protein than do parenchymal cells. This phenomenon is most pronounced for cathepsin D with a 13-times higher specific activity in non-parenchymal cells. Electron microscopic observations demonstrated that the lysosomal activities in non-parenchymal cells can be attributed mainly to the large and numerous lysosomal structures in Kupffer cells. Parenchymal cells from old rats have higher lysosomal enzyme activities per mg protein than do hepatocytes from young rats. This observation is in agreement with the general increase with age in the cytoplasmic volume fraction occupied by lysosomal structures in parenchymal cells. In general, non-parenchymal cells show no increase in specific enzyme activities with age. The results obtained suggest an increase in the heterogeneity--in both appearance and enzyme content--of the lysosomal structures in parenchymal cells with age.", "contents": "Changes in lysosomes during ageing of parenchymal and nonparenchymal liver cells. Intact and viable parenchymal and non-parenchymal liver cell preparations were isolated by enzyme perfusion techniques from young and old rats. The distribution of the lysosomal enzymes acid phosphatase, beta-galactosidase, cathepsin D, acid DNAse, and arylsulphatase B over parenchymal and non-parenchymal cells was determined. In addition, morphological and morphometric changes which occur in parenchymal cells with age were investigated. All lysosomal enzymes studied are present in both cell classes, but non-parenchymal cells possess much ligher activities per mg protein than do parenchymal cells. This phenomenon is most pronounced for cathepsin D with a 13-times higher specific activity in non-parenchymal cells. Electron microscopic observations demonstrated that the lysosomal activities in non-parenchymal cells can be attributed mainly to the large and numerous lysosomal structures in Kupffer cells. Parenchymal cells from old rats have higher lysosomal enzyme activities per mg protein than do hepatocytes from young rats. This observation is in agreement with the general increase with age in the cytoplasmic volume fraction occupied by lysosomal structures in parenchymal cells. In general, non-parenchymal cells show no increase in specific enzyme activities with age. The results obtained suggest an increase in the heterogeneity--in both appearance and enzyme content--of the lysosomal structures in parenchymal cells with age."}
{"id": "PMID:235191", "title": "Experimental mixed infection with two tick-borne viruses and interferon-mediated interference.", "content": "Tick-borne encephalitis virus (TEV), a Flavivirus, and Lipovn\u00edk virus (LV), a member of the Kemerovo group and complex and possible member of the Rioviridae, were used to infect chick embryo cell (CEC) cultures. LV reproduction was inhibited by preinfection with TEV, mainly in aged cultures. In young CEC cultures, TEV production was stimulated slightly and interferon was sometimes depressed by this superinfection; on the contrary, in aged cultures the superinfecting LV stimulated interferon also when infective LV was not produced because of interference. Double staining by the fluorescent antibody (FA) technique localized both viral antigens often in the same cells. Interference between TEV and LV (and vice versa) was observed in cerebrally infected adult mice. The pathogenicity of LV, when injected first, was increased by TEV superinfection. Examination by the FA technique confirmed interference between TEV and LV also in suckling mouse brains and demonstrated both viral antigens in the same brains when TEV and LV were injected simultaneously.", "contents": "Experimental mixed infection with two tick-borne viruses and interferon-mediated interference. Tick-borne encephalitis virus (TEV), a Flavivirus, and Lipovn\u00edk virus (LV), a member of the Kemerovo group and complex and possible member of the Rioviridae, were used to infect chick embryo cell (CEC) cultures. LV reproduction was inhibited by preinfection with TEV, mainly in aged cultures. In young CEC cultures, TEV production was stimulated slightly and interferon was sometimes depressed by this superinfection; on the contrary, in aged cultures the superinfecting LV stimulated interferon also when infective LV was not produced because of interference. Double staining by the fluorescent antibody (FA) technique localized both viral antigens often in the same cells. Interference between TEV and LV (and vice versa) was observed in cerebrally infected adult mice. The pathogenicity of LV, when injected first, was increased by TEV superinfection. Examination by the FA technique confirmed interference between TEV and LV also in suckling mouse brains and demonstrated both viral antigens in the same brains when TEV and LV were injected simultaneously."}
{"id": "PMID:235192", "title": "Small- and large-plaque variants of Chikungunya virus in two vertebrate and seven invertebrate cell lines.", "content": "Nine cells lines--BHK-21, Vero, Aedes albopictus, A. aegypti (monolayer and howwow vesicles), A. w-albus, A. vittatus, Anopheles stephensi and Culex quinquefasciatus--were infected with small- and large-plaque (SP, LP) variants of chikungunya virus. Ross strain, and incubated at different temperatures. In the Aedes (29 plus or minus 1 degrees C) and the vertebrate cell lines (36 degrees C), infectivity titers of extracellular virus rapidly reached a peak; cytopathic effect (CPE) occurred only in the latter. In Anopheles cells (29 plus or minus 1 degrees C), infectivity titers increased very slowly to a peak at 10 days post-inoculation (p.i.); in Culex cells (29 plus or minus 1 degrees C or room temperature), persistence of virus only or no multiplication was observed. In infected A. albopictus, A. aegypti and A. w-albus carrier cultures, the SP variant continued to resemble the original stock virus in terms of mouse pathogenicity and plaque morphology in Vero cells, but the LP variant tended to modify toward the SP variant.", "contents": "Small- and large-plaque variants of Chikungunya virus in two vertebrate and seven invertebrate cell lines. Nine cells lines--BHK-21, Vero, Aedes albopictus, A. aegypti (monolayer and howwow vesicles), A. w-albus, A. vittatus, Anopheles stephensi and Culex quinquefasciatus--were infected with small- and large-plaque (SP, LP) variants of chikungunya virus. Ross strain, and incubated at different temperatures. In the Aedes (29 plus or minus 1 degrees C) and the vertebrate cell lines (36 degrees C), infectivity titers of extracellular virus rapidly reached a peak; cytopathic effect (CPE) occurred only in the latter. In Anopheles cells (29 plus or minus 1 degrees C), infectivity titers increased very slowly to a peak at 10 days post-inoculation (p.i.); in Culex cells (29 plus or minus 1 degrees C or room temperature), persistence of virus only or no multiplication was observed. In infected A. albopictus, A. aegypti and A. w-albus carrier cultures, the SP variant continued to resemble the original stock virus in terms of mouse pathogenicity and plaque morphology in Vero cells, but the LP variant tended to modify toward the SP variant."}
{"id": "PMID:235193", "title": "Experimental latent herpesvirus infection in rabbits, mice and hamsters: ultrastructure of the virus activation in explanted gasseric ganglia.", "content": "The frequency of latent infection as established in trigeminal ganglia of rabbits, mice and hamsters with human herpesvirus type 1 (HVH) was compared using two different virus strains. Explantation proved to be effective in reisolation of HVH from ganglion tissue, which did not yield infectious virus at time of its removal. After healing of acute keratitis, the latent infection in homolateral gasseric ganglia of rabbits was detected at a relatively high frequency (60-80 per cent) up to 120 days post infection (p.i.) in case of both virus strains. The activation rate was a little lower in hamsters. After inoculation of suckling and young mice with a sublethal dose of HVH by oral and nasal routes, approximately 40-100 per cent of the animals had virus in their gasseric ganglia during the acute period; 30-60 days later only 10-25 per cent had virus in the latent form. Immunofluorescent and electron microscopic examination of the explanted ganglion tissue showed the presence of HVH in neurons, neuronal satellites and Schwann cells. The nuclei of noneural cells contained numerous crystalline arrays. The possibility that pseudounipolar neurons of the regional sensoric ganglion are not the exclusive site of HVH latency is discussed.", "contents": "Experimental latent herpesvirus infection in rabbits, mice and hamsters: ultrastructure of the virus activation in explanted gasseric ganglia. The frequency of latent infection as established in trigeminal ganglia of rabbits, mice and hamsters with human herpesvirus type 1 (HVH) was compared using two different virus strains. Explantation proved to be effective in reisolation of HVH from ganglion tissue, which did not yield infectious virus at time of its removal. After healing of acute keratitis, the latent infection in homolateral gasseric ganglia of rabbits was detected at a relatively high frequency (60-80 per cent) up to 120 days post infection (p.i.) in case of both virus strains. The activation rate was a little lower in hamsters. After inoculation of suckling and young mice with a sublethal dose of HVH by oral and nasal routes, approximately 40-100 per cent of the animals had virus in their gasseric ganglia during the acute period; 30-60 days later only 10-25 per cent had virus in the latent form. Immunofluorescent and electron microscopic examination of the explanted ganglion tissue showed the presence of HVH in neurons, neuronal satellites and Schwann cells. The nuclei of noneural cells contained numerous crystalline arrays. The possibility that pseudounipolar neurons of the regional sensoric ganglion are not the exclusive site of HVH latency is discussed."}
{"id": "PMID:235194", "title": "Inhalatory infection of mice with influenza A0/PR8 virus. I. The site of primary virus replication and its spread in the respiratory tract.", "content": "The replication of influenza A0/PR8 virus started and continued simultaneously in all parts of the respiratory tract, without any preferential susceptibility of any area of the epithelial lining when the virus was administered to mice in a sublethal dose in the form of aerosol. After intranasal instillation, the initial virus replication in the lung tissue preceded by 4 to 8 hours the rise in infectious virus titre in the trachea and by 21-24 hours the rise in the virus titre in the nasal mucosa. Under conditions of aersol inhalation, the mice represent a suitable model for pathogenetic studies.", "contents": "Inhalatory infection of mice with influenza A0/PR8 virus. I. The site of primary virus replication and its spread in the respiratory tract. The replication of influenza A0/PR8 virus started and continued simultaneously in all parts of the respiratory tract, without any preferential susceptibility of any area of the epithelial lining when the virus was administered to mice in a sublethal dose in the form of aerosol. After intranasal instillation, the initial virus replication in the lung tissue preceded by 4 to 8 hours the rise in infectious virus titre in the trachea and by 21-24 hours the rise in the virus titre in the nasal mucosa. Under conditions of aersol inhalation, the mice represent a suitable model for pathogenetic studies."}
{"id": "PMID:235195", "title": "Inhalatory infection of mice with influenza A0/PR8 virus. II. Detection of the virus in the blood and extrapulmonary organs.", "content": "In the course of experimental aerosol infection of mice with influenza A virus, the latter was regularly detected in the blood, liver, salivary glands, spleen, pancreas, kidneys, heart and irregularly in cervical and mediastinal lymph nodes. The findings of extrapulmonary virus were in direct quantitative relationship to the rate of lung involvement.", "contents": "Inhalatory infection of mice with influenza A0/PR8 virus. II. Detection of the virus in the blood and extrapulmonary organs. In the course of experimental aerosol infection of mice with influenza A virus, the latter was regularly detected in the blood, liver, salivary glands, spleen, pancreas, kidneys, heart and irregularly in cervical and mediastinal lymph nodes. The findings of extrapulmonary virus were in direct quantitative relationship to the rate of lung involvement."}
{"id": "PMID:235196", "title": "The effect of species and organ-specific features of tissue systems on the reactogenic and immunogenic properties of influenza virus.", "content": "The dynamics of changes in the reactogenic and immunogenic properties of influenza A/Hong Kong/1/68 (H3N2) virus in the course of serial passages in white mice, chick embryos, chick, cow and pig embryo kidney tissue cultures and in rat, guinea pig, chick embryo, cow embryo and pig embryo trachea organ cultures was studied. The rate of virus attenuation was found to depend not only on the species origin of tissue systems but also on their organ specificity. In rapid, 24-hour passages in chick embryos attenuation of the virus developed more rapidly and its immunogenic potency was retained better than in 48-hour passages or cultivation in another tissue system.", "contents": "The effect of species and organ-specific features of tissue systems on the reactogenic and immunogenic properties of influenza virus. The dynamics of changes in the reactogenic and immunogenic properties of influenza A/Hong Kong/1/68 (H3N2) virus in the course of serial passages in white mice, chick embryos, chick, cow and pig embryo kidney tissue cultures and in rat, guinea pig, chick embryo, cow embryo and pig embryo trachea organ cultures was studied. The rate of virus attenuation was found to depend not only on the species origin of tissue systems but also on their organ specificity. In rapid, 24-hour passages in chick embryos attenuation of the virus developed more rapidly and its immunogenic potency was retained better than in 48-hour passages or cultivation in another tissue system."}
{"id": "PMID:235197", "title": "Effect of 60amino-6-deoxy-D-glucose hydrochloride on influenza infection in mice.", "content": "A prophylactic effect of 6-amino-6-deoxy-D-glucose hydrochloride (AG) in influenza-infected mice was demonstrated. A dose of 500 mg AG per kg body-weight given intranasally 2000 mouse intranasal LD50) protected 32-40 per cent of the animals from death. The virus titres in the lungs and serum were lower in treated mice than in untreated ones. After AG administration, low interferon titres were demonstrated in the lungs and serum. The group of infected mice, untreated with AG, was examined electron microscopically. Virus was demonstrated on the surface of granular pneumocytes and in the lumen of lung alveoli.", "contents": "Effect of 60amino-6-deoxy-D-glucose hydrochloride on influenza infection in mice. A prophylactic effect of 6-amino-6-deoxy-D-glucose hydrochloride (AG) in influenza-infected mice was demonstrated. A dose of 500 mg AG per kg body-weight given intranasally 2000 mouse intranasal LD50) protected 32-40 per cent of the animals from death. The virus titres in the lungs and serum were lower in treated mice than in untreated ones. After AG administration, low interferon titres were demonstrated in the lungs and serum. The group of infected mice, untreated with AG, was examined electron microscopically. Virus was demonstrated on the surface of granular pneumocytes and in the lumen of lung alveoli."}
{"id": "PMID:235198", "title": "Phagocytosis-enhancing effect of human leukocyte interferon preparation of human peripheral monocytes in vitro.", "content": "It was found that the phagocytosis of human peripheral monocytes was enhanced by human leukocyte interferon preparations. This activity showed species-specificity and a positive correlation between interferon titer and phagocytic activity. When human monocytes were treated by interferon, the pahagocytic activity was enhanced. But when interferon was added to the latex, the enhancement was not observed. The interferon preparation did not only increase the number of phagocytic cells, but also enhanced the degree of phagocytosis in individual cells. The factor responsible for the enhancing effect was inactivated by trypsin, but was not inhibited by actinomycin D.", "contents": "Phagocytosis-enhancing effect of human leukocyte interferon preparation of human peripheral monocytes in vitro. It was found that the phagocytosis of human peripheral monocytes was enhanced by human leukocyte interferon preparations. This activity showed species-specificity and a positive correlation between interferon titer and phagocytic activity. When human monocytes were treated by interferon, the pahagocytic activity was enhanced. But when interferon was added to the latex, the enhancement was not observed. The interferon preparation did not only increase the number of phagocytic cells, but also enhanced the degree of phagocytosis in individual cells. The factor responsible for the enhancing effect was inactivated by trypsin, but was not inhibited by actinomycin D."}
{"id": "PMID:235199", "title": "Antiviral and cell-growth inhibitory activities of highly purified L-cell interferon. An analysis of quantitative disproportions.", "content": "Purified mouse L-cell interferon induced with Newcastle disease virus was subjected to polyacrylamide gel electrophoresis. A profile characterized by two components was obtained. The faster peak represented about 90-99 per cent of antiviral activity. Both components exerted a cell-growth inhibitory effect on L cells. A study of the quantitative relations between antiviral and cell-growth inhibitory activites of the two peaks revealed a discrepancy between these two activities in the fast peak. An analysis of this phenomenon suggests that the binding capacity of the fast moving molecular species of interferon is lower in young cells than in aged cells, i.e. those incubated for 3 days. Such differences were not observed when the slow molecular species was examined. It was concluded that both inherent properties of molecular components of interferon and the age (and species) of cells used in tests influence the outcome of interferon action on the cell.", "contents": "Antiviral and cell-growth inhibitory activities of highly purified L-cell interferon. An analysis of quantitative disproportions. Purified mouse L-cell interferon induced with Newcastle disease virus was subjected to polyacrylamide gel electrophoresis. A profile characterized by two components was obtained. The faster peak represented about 90-99 per cent of antiviral activity. Both components exerted a cell-growth inhibitory effect on L cells. A study of the quantitative relations between antiviral and cell-growth inhibitory activites of the two peaks revealed a discrepancy between these two activities in the fast peak. An analysis of this phenomenon suggests that the binding capacity of the fast moving molecular species of interferon is lower in young cells than in aged cells, i.e. those incubated for 3 days. Such differences were not observed when the slow molecular species was examined. It was concluded that both inherent properties of molecular components of interferon and the age (and species) of cells used in tests influence the outcome of interferon action on the cell."}
{"id": "PMID:235200", "title": "Ribonuclease-resistant RNA of Kemerovo virus.", "content": "RNA of partially purified Kemerovo virus sedimented in a relatively broad region in sucrose density gradient with a peak at 14 S. Approximately 65% of this RNA was resistant to the action of ribonuclease which indicates the double-stranded nature of Kemerovo virus RNA.", "contents": "Ribonuclease-resistant RNA of Kemerovo virus. RNA of partially purified Kemerovo virus sedimented in a relatively broad region in sucrose density gradient with a peak at 14 S. Approximately 65% of this RNA was resistant to the action of ribonuclease which indicates the double-stranded nature of Kemerovo virus RNA."}
{"id": "PMID:235201", "title": "Synergic action of distamycin A and hydroxyurea on the reproduction of DNA viruses in cell cultures.", "content": "The antiviral activity of the combination of distamycin A (DA) Pand hydroxyurea (HU) on the reproduction of vaccinia and pseudorabies viruses was investigated. The drug combination exerted a significant synergic inhibitory effect on the vaccinia virus yield and on the plaque formation in chick embryo cells. Similar experiments on pseudorabies virus showed an additive effect. The possible mechanism of the mutual enhancement of the antiviral activity is discussed.", "contents": "Synergic action of distamycin A and hydroxyurea on the reproduction of DNA viruses in cell cultures. The antiviral activity of the combination of distamycin A (DA) Pand hydroxyurea (HU) on the reproduction of vaccinia and pseudorabies viruses was investigated. The drug combination exerted a significant synergic inhibitory effect on the vaccinia virus yield and on the plaque formation in chick embryo cells. Similar experiments on pseudorabies virus showed an additive effect. The possible mechanism of the mutual enhancement of the antiviral activity is discussed."}
{"id": "PMID:235202", "title": "Contamination of some avian species with viruses of the leukosis-sarcoma complex.", "content": "Contamination of 8 avian species with leukosis viruses was studied. An insignificant portion of sera from 4 and 24 months old chickens contained neutralizing antibody to 3 sero-types (A, B and D) of Rous sarcoma virus (RSV). Sera from guinea-fowl reacted positively in the neutralization test only with the RSV-RAV-1 strain. None of the Peking duck and semi-domestic Maran fowl sera was found to contain antibody to RSV strains. Twenty-five and 6.6% of embryos derived from 7-8 and 24 to 30 months old chickens respectively, 30% of liver specimens from 3-4 months old chickens 3.3% of liver specimens from adult guinea-fowl and 72% of liver specimens from Maran fowl contained the group-specific leukosis complement-fixing antigen (gs-antigen). Duck embryos and livers from 24-30 months old chickens, crows, sparrows, rooks or jackdaws contained no gs-antigen. Duck embryos did not react and ducklings reacted poorly to inoculation with RSV whereas guinea-fowl embryos and chickens proved to be highly susceptible to RSV.", "contents": "Contamination of some avian species with viruses of the leukosis-sarcoma complex. Contamination of 8 avian species with leukosis viruses was studied. An insignificant portion of sera from 4 and 24 months old chickens contained neutralizing antibody to 3 sero-types (A, B and D) of Rous sarcoma virus (RSV). Sera from guinea-fowl reacted positively in the neutralization test only with the RSV-RAV-1 strain. None of the Peking duck and semi-domestic Maran fowl sera was found to contain antibody to RSV strains. Twenty-five and 6.6% of embryos derived from 7-8 and 24 to 30 months old chickens respectively, 30% of liver specimens from 3-4 months old chickens 3.3% of liver specimens from adult guinea-fowl and 72% of liver specimens from Maran fowl contained the group-specific leukosis complement-fixing antigen (gs-antigen). Duck embryos and livers from 24-30 months old chickens, crows, sparrows, rooks or jackdaws contained no gs-antigen. Duck embryos did not react and ducklings reacted poorly to inoculation with RSV whereas guinea-fowl embryos and chickens proved to be highly susceptible to RSV."}
{"id": "PMID:235203", "title": "Interferon production by rabies strains isolated from wild rodents.", "content": "Eight rabies strains isolated from wild rodents produced interferon in laboratory mouse brains the second day after inoculation. Low levels of interferon were also detected in the serum, kidneys and lungs of the animals. The dosage and route of inoculation had no pronounced effect on interferon production.", "contents": "Interferon production by rabies strains isolated from wild rodents. Eight rabies strains isolated from wild rodents produced interferon in laboratory mouse brains the second day after inoculation. Low levels of interferon were also detected in the serum, kidneys and lungs of the animals. The dosage and route of inoculation had no pronounced effect on interferon production."}
{"id": "PMID:235204", "title": "Comparison of the sensitivity to ultraviolet irradiation of reovirus 3 and some viruses of the Kemerovo group.", "content": "The kinetics of UV inactivation of the tick-borne Kemerovo (strain R-10) and Lipovnik (strain Lip-91) viruses which have been preliminarily classified as possible members of the Reovirus group was examined. Reovirus 3 and Sindbis virus served as reference double-stranded RNA and single-stranded RNA viruses, respectively. The parameters of UV inresembled those of Reovirus 3. This is consistent with their tentative classification as reovirus-like viruses.", "contents": "Comparison of the sensitivity to ultraviolet irradiation of reovirus 3 and some viruses of the Kemerovo group. The kinetics of UV inactivation of the tick-borne Kemerovo (strain R-10) and Lipovnik (strain Lip-91) viruses which have been preliminarily classified as possible members of the Reovirus group was examined. Reovirus 3 and Sindbis virus served as reference double-stranded RNA and single-stranded RNA viruses, respectively. The parameters of UV inresembled those of Reovirus 3. This is consistent with their tentative classification as reovirus-like viruses."}
{"id": "PMID:235208", "title": "Neurohumors in acupuncture.", "content": "In acupuncture an increase of some substance at the reactive site seems to be required in order to have a biochemical response. Among the substances to be considered are the neurohormones. Experimentally, the sympathetic and parasympathetic neurohormones are shown to be involved in analgesia and in the transmission of nerve impulses.", "contents": "Neurohumors in acupuncture. In acupuncture an increase of some substance at the reactive site seems to be required in order to have a biochemical response. Among the substances to be considered are the neurohormones. Experimentally, the sympathetic and parasympathetic neurohormones are shown to be involved in analgesia and in the transmission of nerve impulses."}
{"id": "PMID:235209", "title": "Chemical inhibition method for alkaline phosphatase isoenzymes in human serum.", "content": "The authors adapted a chemical inhibition procedure using L-phenylalanine and urea as specific inhibitors to quantitate the activities of bone, liver, and intestinal alkaline phosphatase (ALP) isoenzymes in human serum. The results of this assay were compared with electrophoretic separation, gamma-glutamyl transpeptidase (GGTP) activity, and the clinical setting in a group of patients with elevated total ALP activity. In addition, expected ranges of serum ALP isoenzymes for healthy young men and also for a geriatric population are presented.", "contents": "Chemical inhibition method for alkaline phosphatase isoenzymes in human serum. The authors adapted a chemical inhibition procedure using L-phenylalanine and urea as specific inhibitors to quantitate the activities of bone, liver, and intestinal alkaline phosphatase (ALP) isoenzymes in human serum. The results of this assay were compared with electrophoretic separation, gamma-glutamyl transpeptidase (GGTP) activity, and the clinical setting in a group of patients with elevated total ALP activity. In addition, expected ranges of serum ALP isoenzymes for healthy young men and also for a geriatric population are presented."}
{"id": "PMID:235212", "title": "Epidemic Venezuelan equine encephalitis in North America in 1971: vector studies.", "content": "A major epidemic of Venezuelan equine encephalitis occurred in south Texas in the summer of 1971. More than 1500 equines died of VEE in Texas, and 110 human cases with no deaths were reported. Vector studies in south Texas and northern Tamaulipas revealed that the overall mosquito infection rates during the peak of the epidemic were about 1:100, one of the highest rates observed for a major epidemic. Mosquito infection rates of this magnitude could easily explain the intensity of VEE outbreaks in both equines and man. A total of 943 VEE virus isolations were made from mosquitoes. Eight of the 12 mosquito species found infected were implicated in the epidemic cycle of VEE for the first time. Sufficient laboratory and field evidence is available to prove that Psorophora confinnis was one of the primary vectors of VEE. The lack of laboratory evidence necessitates the use of the term \"probable\" primary vectors for other species apparently equally as involved on the basis of field infections; these include Aedes sollicitans, Aedes thelcter and Psorophora discolor. Eight other species from which less than 10 VEE virus isolations were made were considered auxiliary vectors. Mosquitoes of some species were tested individually; such tests showed 2-4% of the probable primary vectors to be infected. The first isolation of VEE virus of the epidemic was made from P. confinnis on June 28, 1971. Highest mosquito infection rates occurred during the week of July 5. Mosquito infection rates declined precipitously in the last 3 weeks of July 1971, signaling the end of the epidemic in the study area. One explanation for the decline was that equines, the principal epidemic hosts, were eliminated as a source of virus by death or by acquisition of natural or induced immunity. Mosquito control appeared to be effective in reducing the infected mosquito population while the immunization of equines with TC 83 VEE vaccine was accomplished. Quarantines appeared to be effective in restricting the VEE virus activity to south Texas. Undoubtedly all of the control measures contributed to stopping the epidemic. Continued VEE surveillance by various government and other agencies failed to reveal any further epidemic VEE activity in the US in 1972. Other arboviruses isolated during the VEE studies in south Texas included St. Louis encephalitis virus, and San Angelo subtype of the California Group. A virus of the Bunyamwera Group was also isolated from Palo Blanco, Tamaulipas.", "contents": "Epidemic Venezuelan equine encephalitis in North America in 1971: vector studies. A major epidemic of Venezuelan equine encephalitis occurred in south Texas in the summer of 1971. More than 1500 equines died of VEE in Texas, and 110 human cases with no deaths were reported. Vector studies in south Texas and northern Tamaulipas revealed that the overall mosquito infection rates during the peak of the epidemic were about 1:100, one of the highest rates observed for a major epidemic. Mosquito infection rates of this magnitude could easily explain the intensity of VEE outbreaks in both equines and man. A total of 943 VEE virus isolations were made from mosquitoes. Eight of the 12 mosquito species found infected were implicated in the epidemic cycle of VEE for the first time. Sufficient laboratory and field evidence is available to prove that Psorophora confinnis was one of the primary vectors of VEE. The lack of laboratory evidence necessitates the use of the term \"probable\" primary vectors for other species apparently equally as involved on the basis of field infections; these include Aedes sollicitans, Aedes thelcter and Psorophora discolor. Eight other species from which less than 10 VEE virus isolations were made were considered auxiliary vectors. Mosquitoes of some species were tested individually; such tests showed 2-4% of the probable primary vectors to be infected. The first isolation of VEE virus of the epidemic was made from P. confinnis on June 28, 1971. Highest mosquito infection rates occurred during the week of July 5. Mosquito infection rates declined precipitously in the last 3 weeks of July 1971, signaling the end of the epidemic in the study area. One explanation for the decline was that equines, the principal epidemic hosts, were eliminated as a source of virus by death or by acquisition of natural or induced immunity. Mosquito control appeared to be effective in reducing the infected mosquito population while the immunization of equines with TC 83 VEE vaccine was accomplished. Quarantines appeared to be effective in restricting the VEE virus activity to south Texas. Undoubtedly all of the control measures contributed to stopping the epidemic. Continued VEE surveillance by various government and other agencies failed to reveal any further epidemic VEE activity in the US in 1972. Other arboviruses isolated during the VEE studies in south Texas included St. Louis encephalitis virus, and San Angelo subtype of the California Group. A virus of the Bunyamwera Group was also isolated from Palo Blanco, Tamaulipas."}
{"id": "PMID:235213", "title": "Arbovirus vector ecology studies in Mexico during the 1972 Venezuelan equine encephalitis outbreak.", "content": "Virus vector studies were conducted in the States of Durango, Chihuahua, and Tamaulipas, Mexico, in June and July 1972. Apparently only a low level of Venzuelan equine encephalitis (VEE) virus transmission to equines occured at the time of the study, and the infection was restricted to areas which had not experienced overt activity during the preceding year. The low level of infection was associated with a scarcity of mosquitoes. The IB (epidemic) strain of VEE virus was isolated from two pools of Anopheles pseudopunctipennis (Theo.) and the blood of one symptomatic equine. The low mosquito population, the relatively few equine cases observed, and the absence of reports of VEE human disease from the outbreak area suggested VEE virus persistence through a low-level mosquito-equine transmission cycle. Other studies have already indicated that wild vertebrates play no more than a minor role in outbreaks of epidemic VEE. Mosquito collections made in areas of the states of Durango, Chihuahua, and Tamaulipas, where considerable epidemic activity of VEE had occurred in 1971, failed to reveal evidence of VEE virus persistence. Twenty-nine ioslations of other arboviruses were also made in these studies: including 22 of St. Louis encephalitis virus (SLE), 2 of Flanders virus, 1 of Turlock virus, 1 of Trivittatus virus of the California Group, 1 of western equine encephalitis virus (VEE), and 2 (from Santa Rose) which possibly represent a hitherto unknown virus in the Bunyamwera Group. These are the first reports of SLE virus isolations from mosquitoes in Mexico, and the first demonstration of Trivittatus, VEE Turlock and Flanders viruses in Mexico from any source.", "contents": "Arbovirus vector ecology studies in Mexico during the 1972 Venezuelan equine encephalitis outbreak. Virus vector studies were conducted in the States of Durango, Chihuahua, and Tamaulipas, Mexico, in June and July 1972. Apparently only a low level of Venzuelan equine encephalitis (VEE) virus transmission to equines occured at the time of the study, and the infection was restricted to areas which had not experienced overt activity during the preceding year. The low level of infection was associated with a scarcity of mosquitoes. The IB (epidemic) strain of VEE virus was isolated from two pools of Anopheles pseudopunctipennis (Theo.) and the blood of one symptomatic equine. The low mosquito population, the relatively few equine cases observed, and the absence of reports of VEE human disease from the outbreak area suggested VEE virus persistence through a low-level mosquito-equine transmission cycle. Other studies have already indicated that wild vertebrates play no more than a minor role in outbreaks of epidemic VEE. Mosquito collections made in areas of the states of Durango, Chihuahua, and Tamaulipas, where considerable epidemic activity of VEE had occurred in 1971, failed to reveal evidence of VEE virus persistence. Twenty-nine ioslations of other arboviruses were also made in these studies: including 22 of St. Louis encephalitis virus (SLE), 2 of Flanders virus, 1 of Turlock virus, 1 of Trivittatus virus of the California Group, 1 of western equine encephalitis virus (VEE), and 2 (from Santa Rose) which possibly represent a hitherto unknown virus in the Bunyamwera Group. These are the first reports of SLE virus isolations from mosquitoes in Mexico, and the first demonstration of Trivittatus, VEE Turlock and Flanders viruses in Mexico from any source."}
{"id": "PMID:235214", "title": "Training and function of a women's health-care specialist, a physician's assistant, or nurse practitioner in obstetrics and gynecology.", "content": "Serious manpower shortages exist in the United States. Proposed corrective measures indicate the need for nonphysicians to provide medical care for well or worried well patients. We have tested this proposed solution in the field of obstetrics and gynecology using allied health personnel to provide health maintenance services to well women, and feel that the experiment has been a success. Using principles of pattern recognition allied health workers recognize normal and abnormal findings. Patients with abnormalities are referred to the supervising physician for diagnosis and therapy. Allied health workers can also perform technical health-maintenance tasks such as inserting intrauterine devices and obtaining Pap smears. This article describes the historical evolution of our allied health personnel workers, called women's health-care specialists (WHCS), the selection and training of students, functions and levels of performance of the specialists, and the future role of such individuals in obstetrics and gynecology. We feel that with appropriate preparation of the physician, co-workers, and patients, the integration of the WHCS into the health-care system is both desirable and appropriate and will offer significant advantages to the patient and the practicing obstetrician-gynecologist in either the clinic or private practice setting.", "contents": "Training and function of a women's health-care specialist, a physician's assistant, or nurse practitioner in obstetrics and gynecology. Serious manpower shortages exist in the United States. Proposed corrective measures indicate the need for nonphysicians to provide medical care for well or worried well patients. We have tested this proposed solution in the field of obstetrics and gynecology using allied health personnel to provide health maintenance services to well women, and feel that the experiment has been a success. Using principles of pattern recognition allied health workers recognize normal and abnormal findings. Patients with abnormalities are referred to the supervising physician for diagnosis and therapy. Allied health workers can also perform technical health-maintenance tasks such as inserting intrauterine devices and obtaining Pap smears. This article describes the historical evolution of our allied health personnel workers, called women's health-care specialists (WHCS), the selection and training of students, functions and levels of performance of the specialists, and the future role of such individuals in obstetrics and gynecology. We feel that with appropriate preparation of the physician, co-workers, and patients, the integration of the WHCS into the health-care system is both desirable and appropriate and will offer significant advantages to the patient and the practicing obstetrician-gynecologist in either the clinic or private practice setting."}
{"id": "PMID:235216", "title": "Development of autonomic control of fetal circulation.", "content": "Development of parasympathetic and sympathetic reflexes controlling heart rate, vascular pressures, and blood flows was investigated in fetal lambs weighing 300-5,800 g (65-165 days' gestation). Cardiovascular responses to veratridine injections, atrial stretching, bilateral cervical vagotomy, and cholinergic blockade with atropine were used to test parasympathetic activities. Responses to propranolol and phenoxybenzamine were used to test beta- and alpha-adrenergic activities. Autonomic ganglionic blockade and stimulation provided additional information on both cholinergic and adrenergic systems. Fetal responses to various tests were compared to those of the mother. Results show: a) little parasympathetic tone on resting heart rate and other circulatory functions exists prior to fetal maturity; b) despite the feeble resting tone, the parasympathetic system is capable of exerting significant control when stimulated in both premature and mature fetuses, the capability increases as fetus approaches term; c) alpha- and beta-adrenergic tone in control of resting heart rate and peripheral circulation exists in early fetal life and increases as the fetus reaches maturity, and both adrenergic receptors respond strongly to stimuli in immature, premature, and mature fetuses; d) in immature fetuses, veratridine does not elicit a vagally mediated reflex; instead, it produces a centrally mediated alpha- and beta-adrenergic stimulation; e) the fetal cardiovascular response to any given test is dampened by the existence of the various vascular shunts, the umbilicoplacental circulation and, possibly, by incomplete maturation of vasomotor tone.", "contents": "Development of autonomic control of fetal circulation. Development of parasympathetic and sympathetic reflexes controlling heart rate, vascular pressures, and blood flows was investigated in fetal lambs weighing 300-5,800 g (65-165 days' gestation). Cardiovascular responses to veratridine injections, atrial stretching, bilateral cervical vagotomy, and cholinergic blockade with atropine were used to test parasympathetic activities. Responses to propranolol and phenoxybenzamine were used to test beta- and alpha-adrenergic activities. Autonomic ganglionic blockade and stimulation provided additional information on both cholinergic and adrenergic systems. Fetal responses to various tests were compared to those of the mother. Results show: a) little parasympathetic tone on resting heart rate and other circulatory functions exists prior to fetal maturity; b) despite the feeble resting tone, the parasympathetic system is capable of exerting significant control when stimulated in both premature and mature fetuses, the capability increases as fetus approaches term; c) alpha- and beta-adrenergic tone in control of resting heart rate and peripheral circulation exists in early fetal life and increases as the fetus reaches maturity, and both adrenergic receptors respond strongly to stimuli in immature, premature, and mature fetuses; d) in immature fetuses, veratridine does not elicit a vagally mediated reflex; instead, it produces a centrally mediated alpha- and beta-adrenergic stimulation; e) the fetal cardiovascular response to any given test is dampened by the existence of the various vascular shunts, the umbilicoplacental circulation and, possibly, by incomplete maturation of vasomotor tone."}
{"id": "PMID:235217", "title": "Effects of alveolar and perfusion hypoxia and hypercapnia on pulmonary vascular resistance in the lamb.", "content": "The effects of ventilatory hypoxia and hypercapnia and perfusion hypoxia and hypercapnia on pulmonary vascular resistance were studied in the intact lamb using right heart techniques to isolate and perfuse the left lower lobe. Ventilatory hypoxia increased vascular resistance in the left lower lobe by constricting predominantly vessels upstream from small lobar veins, presumably small arteries. The response to hypoxia was not blocked by phentolamine and diphenhydramine in doses that markedly decreased pressor responses to norepinephrine and histamine in the lung. Perfusion hypoxia did not alter vascular resistance in the perfused lobe. Ventilatory hypercapnia increased vascular resistance in the lung by constricting mainly upstream vessels, whereas perfusion hypercapnia decreased resistance by dilating upstream vessels. These data indicate that histamine and catecholamines are not involved in the response to alveolar hypoxia. These results suggest that the sensor site for ventilatory hypoxia is close to the alveolus since the response is unrelated to lobar arterial Po2. It is concluded that systemic reflexes are not necessarily involved in the response of the pulmonary vascular bed to ventilatory hypoxia or hypercapnia and that the magnitude and rapidity of this response suggest that it may represent an important local mechanism for the control of ventilation-perfusion relationships in this species.", "contents": "Effects of alveolar and perfusion hypoxia and hypercapnia on pulmonary vascular resistance in the lamb. The effects of ventilatory hypoxia and hypercapnia and perfusion hypoxia and hypercapnia on pulmonary vascular resistance were studied in the intact lamb using right heart techniques to isolate and perfuse the left lower lobe. Ventilatory hypoxia increased vascular resistance in the left lower lobe by constricting predominantly vessels upstream from small lobar veins, presumably small arteries. The response to hypoxia was not blocked by phentolamine and diphenhydramine in doses that markedly decreased pressor responses to norepinephrine and histamine in the lung. Perfusion hypoxia did not alter vascular resistance in the perfused lobe. Ventilatory hypercapnia increased vascular resistance in the lung by constricting mainly upstream vessels, whereas perfusion hypercapnia decreased resistance by dilating upstream vessels. These data indicate that histamine and catecholamines are not involved in the response to alveolar hypoxia. These results suggest that the sensor site for ventilatory hypoxia is close to the alveolus since the response is unrelated to lobar arterial Po2. It is concluded that systemic reflexes are not necessarily involved in the response of the pulmonary vascular bed to ventilatory hypoxia or hypercapnia and that the magnitude and rapidity of this response suggest that it may represent an important local mechanism for the control of ventilation-perfusion relationships in this species."}
{"id": "PMID:235218", "title": "Inhibition of angiotensin conversion and prevention of renal hypertension.", "content": "Renal artery constriction in the unilaterally nephrectomized, trained dog, with maintained renal arterial hypotension, produces a prompt increase in systemic renin activity and blood pressure. The hypertension normally induced by renal artery stenosis is prevented by prior treatment with the nonapeptide Pyr-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro (SQ 20, 881), which blocks conversion of angiotensin I to angiotensin II. Constant intravenous infusion of the inhibitor over several days of renal artery constriction prevents the development of chronic renovascular hypertension. Furthermore, a single injection of the nonapeptide restores blood pressure to normal in the early phase of renovascular hypertension, but becomes progressively less effective as salt and water retention occurs in the chronic stage when plasma renin activity returns to control levels. These data provide strong evidence that the renin-angiotensin system is responsible for the initiation of renovascular hypertension in the one-kidney Goldblatt dog, but that other factors become increasingly important in chronic renovascular hypertension.", "contents": "Inhibition of angiotensin conversion and prevention of renal hypertension. Renal artery constriction in the unilaterally nephrectomized, trained dog, with maintained renal arterial hypotension, produces a prompt increase in systemic renin activity and blood pressure. The hypertension normally induced by renal artery stenosis is prevented by prior treatment with the nonapeptide Pyr-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro (SQ 20, 881), which blocks conversion of angiotensin I to angiotensin II. Constant intravenous infusion of the inhibitor over several days of renal artery constriction prevents the development of chronic renovascular hypertension. Furthermore, a single injection of the nonapeptide restores blood pressure to normal in the early phase of renovascular hypertension, but becomes progressively less effective as salt and water retention occurs in the chronic stage when plasma renin activity returns to control levels. These data provide strong evidence that the renin-angiotensin system is responsible for the initiation of renovascular hypertension in the one-kidney Goldblatt dog, but that other factors become increasingly important in chronic renovascular hypertension."}
{"id": "PMID:235219", "title": "Sites of organic acid production and absorption in gastrointestinal tract of the pig.", "content": "The relationship between diet, pH, and microbial digestion of carbohydrate was examined in 24 pigs fed either a conventional or a low-protein, high-cellulose experimental diet and sacrificed 2, 4, 8, or 12 h after a meal. In animals fed the control diet contents of the cranial half of the stomach demonstrated marked, cyclic fluctuations in pH and high concentrations of organic acids. Contents of the caudal (glandular) half were lower in both pH and organic acid concentration. Despite concentrations of volatile fatty acids (VFAs) as high as 250 meq/liter in the large intestine, the pH remained relatively neutral. The VFA levels remained relatively constant throughout the length of the colon. The VFA transport across isolated gastric and large intestinal mucosa also was examined. All four types of gastric mucosa absorbed and transported VFA at substantial rates. Mucosa of pig cecum and colon transported VFA at much greater rates than gastric mucosa and greater rates than previously determined in equine large intestinal mucosa or even bovine rumen epithelium. Comparison with results of earlier studies in the pony suggested that the higher concentration of VFA in the large intestinal contents of pigs was due to the more rapid rate of digesta passage rather than to less efficient absorption of fatty acids.", "contents": "Sites of organic acid production and absorption in gastrointestinal tract of the pig. The relationship between diet, pH, and microbial digestion of carbohydrate was examined in 24 pigs fed either a conventional or a low-protein, high-cellulose experimental diet and sacrificed 2, 4, 8, or 12 h after a meal. In animals fed the control diet contents of the cranial half of the stomach demonstrated marked, cyclic fluctuations in pH and high concentrations of organic acids. Contents of the caudal (glandular) half were lower in both pH and organic acid concentration. Despite concentrations of volatile fatty acids (VFAs) as high as 250 meq/liter in the large intestine, the pH remained relatively neutral. The VFA levels remained relatively constant throughout the length of the colon. The VFA transport across isolated gastric and large intestinal mucosa also was examined. All four types of gastric mucosa absorbed and transported VFA at substantial rates. Mucosa of pig cecum and colon transported VFA at much greater rates than gastric mucosa and greater rates than previously determined in equine large intestinal mucosa or even bovine rumen epithelium. Comparison with results of earlier studies in the pony suggested that the higher concentration of VFA in the large intestinal contents of pigs was due to the more rapid rate of digesta passage rather than to less efficient absorption of fatty acids."}
{"id": "PMID:235220", "title": "Cardiovascular responsiveness to beta-adrenergic stimulation and blockade in chronic hypoxia.", "content": "Previous studies have shown that exposure to high altitude results in an initial increase in heart rate, followed by a return to sea-level values within several days; circulating catecholamines rise progressively during this time. Nine conscious dogs were studied in normoxia (N) and after 10 days' exposure to 445 torr (CH). The mean (plus or minus SE) hematocrit was higher in CH (50 plus or minus 2 vs. 42 plus or minus 1%) while Pa-o2 (53 plus or minus 1 vs. 97 plus or minus 2 torr) and PaCO2 (27 plus or minus 1 vs. 35 plus or minus 1 torr) were lower than in N. A 3.5-fold increase in plasma norepinephrine above the N value was found in CH. Arterial pH, heart rate (HR), and mean femoral arterial pressure (MAP) did not differ significantly in N and CH. Isoproterenol (ISO), 0.5 mug/kg iv, produced an average increase in HR of 92 plus or minus 9 beats/min in N, but only 66 plus or minus 8 beats/min in CH (P smaller than .02). Reduction in MAP after ISO were similar. Pretreatment with propranolol, 0.15 mg/kg iv, reduced HR equally in N and CH without affecting MAP, but diminished the HR response to ISO significantly more in CH than in N. The attenuated chronotropic response to beta-adrenoceptor stimulation following chronic hypobaric hypoxia suggests a relative cardiac refractoriness secondary to an increased level of sympathetic activity.", "contents": "Cardiovascular responsiveness to beta-adrenergic stimulation and blockade in chronic hypoxia. Previous studies have shown that exposure to high altitude results in an initial increase in heart rate, followed by a return to sea-level values within several days; circulating catecholamines rise progressively during this time. Nine conscious dogs were studied in normoxia (N) and after 10 days' exposure to 445 torr (CH). The mean (plus or minus SE) hematocrit was higher in CH (50 plus or minus 2 vs. 42 plus or minus 1%) while Pa-o2 (53 plus or minus 1 vs. 97 plus or minus 2 torr) and PaCO2 (27 plus or minus 1 vs. 35 plus or minus 1 torr) were lower than in N. A 3.5-fold increase in plasma norepinephrine above the N value was found in CH. Arterial pH, heart rate (HR), and mean femoral arterial pressure (MAP) did not differ significantly in N and CH. Isoproterenol (ISO), 0.5 mug/kg iv, produced an average increase in HR of 92 plus or minus 9 beats/min in N, but only 66 plus or minus 8 beats/min in CH (P smaller than .02). Reduction in MAP after ISO were similar. Pretreatment with propranolol, 0.15 mg/kg iv, reduced HR equally in N and CH without affecting MAP, but diminished the HR response to ISO significantly more in CH than in N. The attenuated chronotropic response to beta-adrenoceptor stimulation following chronic hypobaric hypoxia suggests a relative cardiac refractoriness secondary to an increased level of sympathetic activity."}
{"id": "PMID:235221", "title": "Relations of weak-electrolyte transport and acid-base metabolism in rat small intestine in vitro.", "content": "The jejunal and ileal regions of rat small intestine in vitro exhibit different patterns of weak-electrolyte transport and acid-base metabolism. The jejunal pattern of weak-electrolyte transport is net transport of weak acids M yields S and of weak bases S yields M (M, mucosal; S, serosal), and the pattern of acid-base metabolism is luminal acidification and serosal alkalinization. In the absence of sodium or in the presence of metabolic inhibitors, weak-electrolyte transport and serosal alkalinization are inhibited, but luminal acidification is not inhibited. The ileal pattern of weak-electrolyte transport is the opposite of that of the jejunum and may be associated with the presence of a luminal alkalinization process observed in this region. In the absence of chloride the ileal patterns of weak-electrolyte transport and acid-base metabolism become similar to those of the jejunum. It is suggested that these observations support a previously proposed model for weak-electrolyte transport in the intestine consisting of a series three-compartment system in which the pH of the intermediate compartment is greater than that of the bulk phases.", "contents": "Relations of weak-electrolyte transport and acid-base metabolism in rat small intestine in vitro. The jejunal and ileal regions of rat small intestine in vitro exhibit different patterns of weak-electrolyte transport and acid-base metabolism. The jejunal pattern of weak-electrolyte transport is net transport of weak acids M yields S and of weak bases S yields M (M, mucosal; S, serosal), and the pattern of acid-base metabolism is luminal acidification and serosal alkalinization. In the absence of sodium or in the presence of metabolic inhibitors, weak-electrolyte transport and serosal alkalinization are inhibited, but luminal acidification is not inhibited. The ileal pattern of weak-electrolyte transport is the opposite of that of the jejunum and may be associated with the presence of a luminal alkalinization process observed in this region. In the absence of chloride the ileal patterns of weak-electrolyte transport and acid-base metabolism become similar to those of the jejunum. It is suggested that these observations support a previously proposed model for weak-electrolyte transport in the intestine consisting of a series three-compartment system in which the pH of the intermediate compartment is greater than that of the bulk phases."}
{"id": "PMID:235222", "title": "Effect of methylprednisolone upon arterial pressure and the renin angiotensin system in the rat.", "content": "The effect of methylprednisolone or deoxycorticosterone upon systemic arterial blood pressure and components of the renin-angiotensin system was studied in the rat. Rats maintained on regular diets given methylprednisolone suspension 20 mg/kg body wt demonstrated a significant increase in arterial pressure of + 37 plus or minus 5 mmHg, mean plus or minus SE, over a 2-wk period, whereas those treated with DOC and untreated controls showed no significant change. On normal diets, plasma renin concentration (PRC) of methylprednisolone-treated rats was significantly higher than that of DOC-treated rats. Methylprednisolone treatment also resulted in a significant elevation of plasma renin substrate concentration (PRS). Calculated plasma renin activity (PRA) was highest in methylprednisolone-treated rats, significantly above that of the DOC and no-steroid groups. NaCl supplementation resulted in a significant fall in PRC and PRA in all three groups; however, PRS remained significantly above normal in the methylprednisolone-treated rats. The pressor effect of angiotensin II was slightly increased in methylprednisolone-treated rats. Infusion of [Sar1,Ala8]angiotensin II (P-113) in methylprednisolone-treated rats resulted in a significant fall in diastolic arterial pressure. The results imply that methylprednisolone hypertension in the rat may be in part angiotensin dependent.", "contents": "Effect of methylprednisolone upon arterial pressure and the renin angiotensin system in the rat. The effect of methylprednisolone or deoxycorticosterone upon systemic arterial blood pressure and components of the renin-angiotensin system was studied in the rat. Rats maintained on regular diets given methylprednisolone suspension 20 mg/kg body wt demonstrated a significant increase in arterial pressure of + 37 plus or minus 5 mmHg, mean plus or minus SE, over a 2-wk period, whereas those treated with DOC and untreated controls showed no significant change. On normal diets, plasma renin concentration (PRC) of methylprednisolone-treated rats was significantly higher than that of DOC-treated rats. Methylprednisolone treatment also resulted in a significant elevation of plasma renin substrate concentration (PRS). Calculated plasma renin activity (PRA) was highest in methylprednisolone-treated rats, significantly above that of the DOC and no-steroid groups. NaCl supplementation resulted in a significant fall in PRC and PRA in all three groups; however, PRS remained significantly above normal in the methylprednisolone-treated rats. The pressor effect of angiotensin II was slightly increased in methylprednisolone-treated rats. Infusion of [Sar1,Ala8]angiotensin II (P-113) in methylprednisolone-treated rats resulted in a significant fall in diastolic arterial pressure. The results imply that methylprednisolone hypertension in the rat may be in part angiotensin dependent."}
{"id": "PMID:235223", "title": "Induction of a myogenic response in tonic airway smooth muscle by tetraethylammonium.", "content": "In multi-unit tracheal smooth muscle (TSM), quick stretches applied at a velocity of 5 times the measured maximum velocity of isotonic shortening of the muscle, of a magnitude 3 times the measured extension of the series-elastic component when the muscle contracts maximally, and at optimal muscle length (L-o) were unable to elicit any myogenic response (MR). Experimental conditions such as hypoxia (P-O2 smaller than 60 mmHg) and acidosis (pH equals 6.8) or the presence of Ba2+ (2 mM), acetylcholine (10-6 M), or high (K+)-o (59 mM) were also unable to elicit the MR. However, tetraethylammonium chloride (TEA, 0.4-67 mM) produces 1) spontaneous phasic contractions and 2) a MR to quick stretch. The ionic basis for these changes was then investigated by studying the Ca and Mg dependence of the response to TEA. The dose-response relationship to TEA was shifted to the left by decreasing external Mg2+ from 2.5 to 0.5 mM. The ability of TSM to produce a MR was absolutely dependent on external Ca, but the threshold concentration required shifted from 2.5 times 10-5 M at normal external Mg (2.5 mM) to 5 times 10-4 M at the reduced external Mg (0.5 mM). The effects of TEA on spontaneity and the MR were abolished by D-600. These results suggest that 1) TEA functionally converts multiunit smooth muscle into a single unit one and leads to the development of a MR and 2) the MR results from a depolarization-activated mobilization of Ca and is inhibited by ionic conditions known to increase membrane permeability.", "contents": "Induction of a myogenic response in tonic airway smooth muscle by tetraethylammonium. In multi-unit tracheal smooth muscle (TSM), quick stretches applied at a velocity of 5 times the measured maximum velocity of isotonic shortening of the muscle, of a magnitude 3 times the measured extension of the series-elastic component when the muscle contracts maximally, and at optimal muscle length (L-o) were unable to elicit any myogenic response (MR). Experimental conditions such as hypoxia (P-O2 smaller than 60 mmHg) and acidosis (pH equals 6.8) or the presence of Ba2+ (2 mM), acetylcholine (10-6 M), or high (K+)-o (59 mM) were also unable to elicit the MR. However, tetraethylammonium chloride (TEA, 0.4-67 mM) produces 1) spontaneous phasic contractions and 2) a MR to quick stretch. The ionic basis for these changes was then investigated by studying the Ca and Mg dependence of the response to TEA. The dose-response relationship to TEA was shifted to the left by decreasing external Mg2+ from 2.5 to 0.5 mM. The ability of TSM to produce a MR was absolutely dependent on external Ca, but the threshold concentration required shifted from 2.5 times 10-5 M at normal external Mg (2.5 mM) to 5 times 10-4 M at the reduced external Mg (0.5 mM). The effects of TEA on spontaneity and the MR were abolished by D-600. These results suggest that 1) TEA functionally converts multiunit smooth muscle into a single unit one and leads to the development of a MR and 2) the MR results from a depolarization-activated mobilization of Ca and is inhibited by ionic conditions known to increase membrane permeability."}
{"id": "PMID:235226", "title": "Pacui virus, phlebotomine flies, and small mammals in Brazil: an epidemiological study.", "content": "Pacui virus, originally obtained from forest rodents, was isolated 100 times from 61,437 specimens (658 pools) of the phlebotomine fly Lutzomyia flaviscutellata, collected from rodent-baited traps in the forests of Belem, Para, Brazil in the period October 1968 through September 1970. Isolations were made from engorged and unengorged females and from males (3 strains), and occurred in all 24 months. Pacui virus also was isolated from the blood of two wild rodents (Oryzomys), but not from 424 L. infraspinosa, 12,000 mosquitoes, or sentinel mice. Pacui virus neutralizing antibodies were detected in serum of six bait animals after exposure to biting flies in the forest, in 30% of wild rodents surveyed (including two from Amapa Territory), and in 10% of marsupials, but were absent in human survey sera and in bats. Low-passage Pacui virus produced viremia in and was lethal to infant mice by the subcutaneous route. L. flaviscutellata was most abundant in the dry season, in which period Pacui virus isolations increased. This fly is strongly attracted to rodents close to the ground. L. flaviscutellata also yielded single strains of Guama, Icoaraci, and BeAr 177325 viruses.", "contents": "Pacui virus, phlebotomine flies, and small mammals in Brazil: an epidemiological study. Pacui virus, originally obtained from forest rodents, was isolated 100 times from 61,437 specimens (658 pools) of the phlebotomine fly Lutzomyia flaviscutellata, collected from rodent-baited traps in the forests of Belem, Para, Brazil in the period October 1968 through September 1970. Isolations were made from engorged and unengorged females and from males (3 strains), and occurred in all 24 months. Pacui virus also was isolated from the blood of two wild rodents (Oryzomys), but not from 424 L. infraspinosa, 12,000 mosquitoes, or sentinel mice. Pacui virus neutralizing antibodies were detected in serum of six bait animals after exposure to biting flies in the forest, in 30% of wild rodents surveyed (including two from Amapa Territory), and in 10% of marsupials, but were absent in human survey sera and in bats. Low-passage Pacui virus produced viremia in and was lethal to infant mice by the subcutaneous route. L. flaviscutellata was most abundant in the dry season, in which period Pacui virus isolations increased. This fly is strongly attracted to rodents close to the ground. L. flaviscutellata also yielded single strains of Guama, Icoaraci, and BeAr 177325 viruses."}
{"id": "PMID:235227", "title": "The effect of acid-base balance on neostigmine antagonism of d-tubocurarine-induced neuromuscular blockade.", "content": "d-Tubocurarine (dTc) was infused intravenously into 35 cats anesthetized with chloralose and urethane at a constant continuous rate to produce and maintain 90 per cent depression of twitch height of the anterior tibial muscle following supramaximal stimulation of the peroneal nerve. The mean infusion rates that produced 90 per cent depression were not significantly altered by respiratory acid-base changes. Metabolic alkalosis decreased (32.5 per cent) and metabolic acidosis increased (27.7 per cent) the required infusion rate of dTc. When pH and Paco2 were maintained at 7.37 and 38 torr, respectively, the addition of a bolus of neostigmine, 10.5 mug/kg, intravenously, to the continuing infusion of dTc produced 50 per cent antagonism of the dTc-depressed twitch. Respiratory alkalosis and metabolic acidosis did not alter the dose of neostigmine needed to produce 50 per cent antagonism. However, during respiratory acidosis (pH 7.13, Paco2 66 torr) and metabolic alkalosis (pH 7.59, Paco2 36 torr) 20.0 and 18.0 mug/kg neostigmine, respectively, were needed to produce 50 per cent antagonism. Still larger doses of neostigmine (75 mug/kg) could not completely antagonize the block unless pH and Paco2 were returned to 7.30-7.50 and 35-45 torr, respectively. It is concluded that respiratory acidosis and metabolic alkalosis limit and oppose antagonism of dTc by neostigmine.", "contents": "The effect of acid-base balance on neostigmine antagonism of d-tubocurarine-induced neuromuscular blockade. d-Tubocurarine (dTc) was infused intravenously into 35 cats anesthetized with chloralose and urethane at a constant continuous rate to produce and maintain 90 per cent depression of twitch height of the anterior tibial muscle following supramaximal stimulation of the peroneal nerve. The mean infusion rates that produced 90 per cent depression were not significantly altered by respiratory acid-base changes. Metabolic alkalosis decreased (32.5 per cent) and metabolic acidosis increased (27.7 per cent) the required infusion rate of dTc. When pH and Paco2 were maintained at 7.37 and 38 torr, respectively, the addition of a bolus of neostigmine, 10.5 mug/kg, intravenously, to the continuing infusion of dTc produced 50 per cent antagonism of the dTc-depressed twitch. Respiratory alkalosis and metabolic acidosis did not alter the dose of neostigmine needed to produce 50 per cent antagonism. However, during respiratory acidosis (pH 7.13, Paco2 66 torr) and metabolic alkalosis (pH 7.59, Paco2 36 torr) 20.0 and 18.0 mug/kg neostigmine, respectively, were needed to produce 50 per cent antagonism. Still larger doses of neostigmine (75 mug/kg) could not completely antagonize the block unless pH and Paco2 were returned to 7.30-7.50 and 35-45 torr, respectively. It is concluded that respiratory acidosis and metabolic alkalosis limit and oppose antagonism of dTc by neostigmine."}
{"id": "PMID:235228", "title": "MAC expanded: AD50 and AD95 values of common inhalation anesthetics in man.", "content": "Two important measures may be derived from patient responses to a range of anesthetic doses. The AD50, corresponding to MAC, estimates the median anesthetic concentration--that dose where half the patients are anesthetized and half are not. The AD95 approaches the theoretical \"minimum\" anesthetic concentration by estimating the dose that anesthetizes 95 per cent of a patient population. The AD50 and AD95 are logical extensions of the MAC concept and can be evaluated with current experimental methodology. Recomputed from available data , the AD50's of nine inhaled anesthetics proved to be numerically identical to their MAC values. The AD95's of nine inhaled anesthetics proved to be numerically identical to their MAC values. The AD95's were 5 to 40 per cent greater than the AD50's.)Key workd: Potency, anesthetic, MAC, AD50, AD95; Pharmacology, dose-response curves.)", "contents": "MAC expanded: AD50 and AD95 values of common inhalation anesthetics in man. Two important measures may be derived from patient responses to a range of anesthetic doses. The AD50, corresponding to MAC, estimates the median anesthetic concentration--that dose where half the patients are anesthetized and half are not. The AD95 approaches the theoretical \"minimum\" anesthetic concentration by estimating the dose that anesthetizes 95 per cent of a patient population. The AD50 and AD95 are logical extensions of the MAC concept and can be evaluated with current experimental methodology. Recomputed from available data , the AD50's of nine inhaled anesthetics proved to be numerically identical to their MAC values. The AD95's of nine inhaled anesthetics proved to be numerically identical to their MAC values. The AD95's were 5 to 40 per cent greater than the AD50's.)Key workd: Potency, anesthetic, MAC, AD50, AD95; Pharmacology, dose-response curves.)"}
{"id": "PMID:235229", "title": "Effects of peridural block: V. Properties, circulatory effects, and blood levels of etidocaine and lidocaine.", "content": "Ten healthy, unpremedicated, male volunteers, aged 21-33 years, were given 20 ml 1 per cent etidocaine with 5 mug/ml epinephrine for peridural analgesia via a catheter placed L2. On a different occasion they were given 20 ml 2 per cent lidocaine with 5 mug/ml epinephrine in the same manner. Initial onset of sensory analgesia to pin prick was faster for etidocaine (7 min) than for lidocaine (9 min). Analgesia lasted significantly longer after etidocaine with respect to both two-segment regression (177 plus or minus SE min vs. 114 plus or minus 8 min) and total duration (379 plus or minus 22 min vs. 190 plus or minus 8 min). Onset of maximal motor blockade was significantly faster with etidocaine (15.4 plus or minus 2.5 min) than with lidocaine (31.7 plus or minus 3.3 min); blockade lasted longer with etidocaine (331 plus or minus 25 min vs. 167 plus or minus 13 min). Changes in mean arterial pressure cardiac output, central venous pressure, limb blood flows, total peripheral resistance, and stroke volume were similar with the two drugs, although those after etidocaine were more prolonged as a result of the longer blockade. Mean maximum arterial concentrations of etidocaine were 0.96 plus or minus 0.05 SE mug/ml (plasma) and 0.55 plus or minus 0.03 mug/ml (whold blood), achieved at 17 plus or minus 2 min. Mean maximum arterial concentrations of lidocaine were 2.22 plus or minus 0.09 mug/ml (plasma) and 1.85 plus or minus mug/ml (whold blood), achieved at 24 plus or minus 2 min. No sign of central toxicity was observed with either drug, although subjects receiving lidocaine tended to sleep, which was not the case with etidocaine. Hematologic screening, blood chemistries, and urinalyses performed 24 hours before and after each study showed no abnormality.", "contents": "Effects of peridural block: V. Properties, circulatory effects, and blood levels of etidocaine and lidocaine. Ten healthy, unpremedicated, male volunteers, aged 21-33 years, were given 20 ml 1 per cent etidocaine with 5 mug/ml epinephrine for peridural analgesia via a catheter placed L2. On a different occasion they were given 20 ml 2 per cent lidocaine with 5 mug/ml epinephrine in the same manner. Initial onset of sensory analgesia to pin prick was faster for etidocaine (7 min) than for lidocaine (9 min). Analgesia lasted significantly longer after etidocaine with respect to both two-segment regression (177 plus or minus SE min vs. 114 plus or minus 8 min) and total duration (379 plus or minus 22 min vs. 190 plus or minus 8 min). Onset of maximal motor blockade was significantly faster with etidocaine (15.4 plus or minus 2.5 min) than with lidocaine (31.7 plus or minus 3.3 min); blockade lasted longer with etidocaine (331 plus or minus 25 min vs. 167 plus or minus 13 min). Changes in mean arterial pressure cardiac output, central venous pressure, limb blood flows, total peripheral resistance, and stroke volume were similar with the two drugs, although those after etidocaine were more prolonged as a result of the longer blockade. Mean maximum arterial concentrations of etidocaine were 0.96 plus or minus 0.05 SE mug/ml (plasma) and 0.55 plus or minus 0.03 mug/ml (whold blood), achieved at 17 plus or minus 2 min. Mean maximum arterial concentrations of lidocaine were 2.22 plus or minus 0.09 mug/ml (plasma) and 1.85 plus or minus mug/ml (whold blood), achieved at 24 plus or minus 2 min. No sign of central toxicity was observed with either drug, although subjects receiving lidocaine tended to sleep, which was not the case with etidocaine. Hematologic screening, blood chemistries, and urinalyses performed 24 hours before and after each study showed no abnormality."}
{"id": "PMID:235230", "title": "Pulmonary shunting during alveolar hypoventilation in the dog.", "content": "Pulmonary shunting (Qs/Qt) was measured in 16 anesthetized and paralyzed healthy beagle puppies during a control period when the end-expired CO2 concentration was 5 per cent and during alveolar hypoventilation, when the PaCO2 increased to 100 plus or minus 13 torr (mean plus or minus SE) and the ;Ha vecame 7.04 plus or minus 0.04. A constant tidal volume was maintained throughout each study, and hypoventilation was achieved by slowing only the respiratory rate. During the control period Qs/Qt was 2.9 plus or minus 0.3 per cent; during hypoventilation Qs/Qt was 3.2 plus or minus 0.3 per cent (an insignificant difference). The puppies, therefore, responded to anesthesia and alveolar hypoventilation without development of increased pulmonary shunts.", "contents": "Pulmonary shunting during alveolar hypoventilation in the dog. Pulmonary shunting (Qs/Qt) was measured in 16 anesthetized and paralyzed healthy beagle puppies during a control period when the end-expired CO2 concentration was 5 per cent and during alveolar hypoventilation, when the PaCO2 increased to 100 plus or minus 13 torr (mean plus or minus SE) and the ;Ha vecame 7.04 plus or minus 0.04. A constant tidal volume was maintained throughout each study, and hypoventilation was achieved by slowing only the respiratory rate. During the control period Qs/Qt was 2.9 plus or minus 0.3 per cent; during hypoventilation Qs/Qt was 3.2 plus or minus 0.3 per cent (an insignificant difference). The puppies, therefore, responded to anesthesia and alveolar hypoventilation without development of increased pulmonary shunts."}
{"id": "PMID:235231", "title": "Smoking as a cause of erythrocytosis.", "content": "Five smokers had erythrocyte masses sufficiently larger than normal to pose a problem in the differential diagnosis of polycythemia. Evaluation excluded lung disease, shunt physiology, hemoglobin with increased oxygen affinity, erythropoietin-producing tumor, renal disease, or polycythemia rubra vera as the primary cause of erythrocytosis in these patients. All were found to have levels of carboxyhemoglobin sufficient to cause clinically significant hypoxemia and to account for the increased erythrocyte masses. In two patients the erythrocytosis improved when they stopped smoking. Heavy smoking is a reversible cause of polycythemia and should be considered in the differential diagnosis of this problem.", "contents": "Smoking as a cause of erythrocytosis. Five smokers had erythrocyte masses sufficiently larger than normal to pose a problem in the differential diagnosis of polycythemia. Evaluation excluded lung disease, shunt physiology, hemoglobin with increased oxygen affinity, erythropoietin-producing tumor, renal disease, or polycythemia rubra vera as the primary cause of erythrocytosis in these patients. All were found to have levels of carboxyhemoglobin sufficient to cause clinically significant hypoxemia and to account for the increased erythrocyte masses. In two patients the erythrocytosis improved when they stopped smoking. Heavy smoking is a reversible cause of polycythemia and should be considered in the differential diagnosis of this problem."}
{"id": "PMID:235232", "title": "Drug spotlight program: antacids and anticholinergic drugs.", "content": "Controlled clinical trials have provided some useful evidence of the effectiveness or lack of effectiveness of antacids and anticholinergic drugs. However, few such trials are free of serious methodologic or clinical criticism, and the use of these agents cannot be defined with any degree of scientific certainty. Their principal uses still focus on reduction of gastric acid content, and their best use requires individualization for each patient. With anticholinergic drugs there is little if any pharmacologic effect without some side-effects, and dose adjustment may be more important than the choice among the many drugs considered effective. Some new antacids offer better neutralization than old ones, but are at least as likely to affect colonic function. Although toxicity, side-effects, and interactions with other drugs are minimal, they should be watched for.", "contents": "Drug spotlight program: antacids and anticholinergic drugs. Controlled clinical trials have provided some useful evidence of the effectiveness or lack of effectiveness of antacids and anticholinergic drugs. However, few such trials are free of serious methodologic or clinical criticism, and the use of these agents cannot be defined with any degree of scientific certainty. Their principal uses still focus on reduction of gastric acid content, and their best use requires individualization for each patient. With anticholinergic drugs there is little if any pharmacologic effect without some side-effects, and dose adjustment may be more important than the choice among the many drugs considered effective. Some new antacids offer better neutralization than old ones, but are at least as likely to affect colonic function. Although toxicity, side-effects, and interactions with other drugs are minimal, they should be watched for."}
{"id": "PMID:235236", "title": "Cholecystectomy and gallstone dyspepsia. Clinical and physiological study of a symptom complex.", "content": "The symptom complex of gallstone dyspepsia is defined and then analysed before and after cholecystectomy in 108 patients. Only 46% of patients were symptom-free after operation and 30% were no better. When pyloric function was studied patients with these symptoms before or after cholecystectomy and those with normal radiographs showed duodenogastric reflux, often precipitated by intraduodenal fat. Symptomless matched control subjects showed no reflux. Synchronous radiology and pressure recordings demonstrated that the pylorus in these patients failed to contract in response to a duodenal contraction, whereas the normal pylorus could prevent the reflux produced by an isolated duodenal contraction. The effect of metoclopramide on gastroduodenal contractions and in treating the symptoms was assessed. Gallstone dyspepsia is essentially a functional disease--a disorder of gastroduodenal motility.", "contents": "Cholecystectomy and gallstone dyspepsia. Clinical and physiological study of a symptom complex. The symptom complex of gallstone dyspepsia is defined and then analysed before and after cholecystectomy in 108 patients. Only 46% of patients were symptom-free after operation and 30% were no better. When pyloric function was studied patients with these symptoms before or after cholecystectomy and those with normal radiographs showed duodenogastric reflux, often precipitated by intraduodenal fat. Symptomless matched control subjects showed no reflux. Synchronous radiology and pressure recordings demonstrated that the pylorus in these patients failed to contract in response to a duodenal contraction, whereas the normal pylorus could prevent the reflux produced by an isolated duodenal contraction. The effect of metoclopramide on gastroduodenal contractions and in treating the symptoms was assessed. Gallstone dyspepsia is essentially a functional disease--a disorder of gastroduodenal motility."}
{"id": "PMID:235237", "title": "[Carbon metabolism under conditions of regulated penicillin biosynthesis].", "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": "[Carbon metabolism under conditions of regulated penicillin biosynthesis]. 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:235238", "title": "[Rate of benyzylpenicillin inactivation in native solutions during extraction].", "content": "The constants of benzylpenicillin inactivation in acidified fermentation broth filtrates were different in various filtrate batches. Marked inactivation of the antibiotic in the filtrates immediately after their acidification was observed. Possible losses of the antibiotic due to inactivation under conditions of extraction were estimated.", "contents": "[Rate of benyzylpenicillin inactivation in native solutions during extraction]. The constants of benzylpenicillin inactivation in acidified fermentation broth filtrates were different in various filtrate batches. Marked inactivation of the antibiotic in the filtrates immediately after their acidification was observed. Possible losses of the antibiotic due to inactivation under conditions of extraction were estimated."}
{"id": "PMID:235239", "title": "[Quantitative method for determining variamycin].", "content": "A quantitative spectrophotmetric method for the assay of variamycin in commercial samples was developed. It was based on the measurement of the optical density of variamycin solutions in 0.01 N hydrochloric acid at a UV spectrum wave length of 412 nm. A method of thin-layer chromatography for a semi-quantitative estimation of tetraside, the main admixture of variamycin was devised. On storage for 18 months the content of variamycin in the preparations did not change as compared to that at the moment of the drug manufacturing and the amount of tetraside in 18 months did not exceed 2 per cent.", "contents": "[Quantitative method for determining variamycin]. A quantitative spectrophotmetric method for the assay of variamycin in commercial samples was developed. It was based on the measurement of the optical density of variamycin solutions in 0.01 N hydrochloric acid at a UV spectrum wave length of 412 nm. A method of thin-layer chromatography for a semi-quantitative estimation of tetraside, the main admixture of variamycin was devised. On storage for 18 months the content of variamycin in the preparations did not change as compared to that at the moment of the drug manufacturing and the amount of tetraside in 18 months did not exceed 2 per cent."}
{"id": "PMID:235243", "title": "Chromosome mutations and pH disturbances.", "content": "Chromosomal anomalies, namely hypodiploidies, hyperdiploidies, and endoreduplications, developed in nearly 25% of metaphase plates of replicating human lymphocytes exposed in vitro to either acid (6.5 to 6.9) or alkaline (8.4 to 8.8) pH equilibriums. The G group was most susceptible to aneuploid formation. Mammalian mutations may develop as the result of a pH disturbance during cleavage of the fertilized zygote.", "contents": "Chromosome mutations and pH disturbances. Chromosomal anomalies, namely hypodiploidies, hyperdiploidies, and endoreduplications, developed in nearly 25% of metaphase plates of replicating human lymphocytes exposed in vitro to either acid (6.5 to 6.9) or alkaline (8.4 to 8.8) pH equilibriums. The G group was most susceptible to aneuploid formation. Mammalian mutations may develop as the result of a pH disturbance during cleavage of the fertilized zygote."}
{"id": "PMID:235244", "title": "CO2 fixation and its regulation in Anacystis nidulans (Synechococcus).", "content": "Anacystis nidulans (Synechococcus) had a minimal doubling time of 5 hrs at 30 degrees C at saturating light intensity and carbon dioxide concentration. Half maximal growth rates in saturating CO2 occured at a light intensity of 0.54 mW per cm2, and there was an apparent threshold intensity of 0.13 mW per cm2 below which no growth occurred. Growth rate in saturating light was dependent on the concentration of CO2+H2CO3 in the medium, rather than on total dissolved CO2; half maximal rates were estimated at 0.1 mM CO2+H2CO3. Under saturating conditions of light and CO2, 14CO2 was fixed primarily into 3-PGA, and subsequently moved into sugar phosphates and amino acids. Incorporation into aspartate was relatively slow. CO2 fixation was strictly light-dependent. The changes in adenylate and pyridine nucleotide pools were followed in light/dark and dark/light transitions. Whereas adenylates relaxed slowly over 15-20 min to the concentrations characteristic of illuminated cells following the abrupt changes induced by darkening, the sharp drop in intracellular NADPH showed little dark recovery although rapid restoration occurred on reillumination. Other pyridine nucleotides showed no changes during these transitions. The nucleotide specificity and Km of partially purfied GAP dehydrogenase suggest a role for this enzyme in the regulation of CO2 fixation.", "contents": "CO2 fixation and its regulation in Anacystis nidulans (Synechococcus). Anacystis nidulans (Synechococcus) had a minimal doubling time of 5 hrs at 30 degrees C at saturating light intensity and carbon dioxide concentration. Half maximal growth rates in saturating CO2 occured at a light intensity of 0.54 mW per cm2, and there was an apparent threshold intensity of 0.13 mW per cm2 below which no growth occurred. Growth rate in saturating light was dependent on the concentration of CO2+H2CO3 in the medium, rather than on total dissolved CO2; half maximal rates were estimated at 0.1 mM CO2+H2CO3. Under saturating conditions of light and CO2, 14CO2 was fixed primarily into 3-PGA, and subsequently moved into sugar phosphates and amino acids. Incorporation into aspartate was relatively slow. CO2 fixation was strictly light-dependent. The changes in adenylate and pyridine nucleotide pools were followed in light/dark and dark/light transitions. Whereas adenylates relaxed slowly over 15-20 min to the concentrations characteristic of illuminated cells following the abrupt changes induced by darkening, the sharp drop in intracellular NADPH showed little dark recovery although rapid restoration occurred on reillumination. Other pyridine nucleotides showed no changes during these transitions. The nucleotide specificity and Km of partially purfied GAP dehydrogenase suggest a role for this enzyme in the regulation of CO2 fixation."}
{"id": "PMID:235245", "title": "Differential fluorescence labelling with 5-dimethyl-aminonaphthalene-1-sulfonyl chloride of intact cells and isolated membranes in Salmonella typhimurium and Acholeplasma laidlawii.", "content": "For fluorescence labelling intact cells and isolated cell envelopes (membranes) from Salmonella typhimurium and Acholeplasma laidlawii were treated with mixed dansylchloride-lecithin-cholesterol vesicles. This kind of dansylation, which has been supposed to be specific for cell surface proteins, produced fluorescent protein pattern after SDS-polyacrylamide gel electrophoresis only when isolated envelopes were dansylated. Acid hydrolysis of fluorescent cell envelopes of Salmonella typhimurium yielded O-dansyltryosine and epsilon-N-dansyl-lysine besides the free sulfonic acid and unidentified compounds. However, no fluorescent proteins were detectable in cell envelopes isolated from dansylated intact bacteria from Salmonella typhimurium. In accord Acholeplasma laidlawii showed only fluorescence from proteins with a molecular weight higher than 100000.", "contents": "Differential fluorescence labelling with 5-dimethyl-aminonaphthalene-1-sulfonyl chloride of intact cells and isolated membranes in Salmonella typhimurium and Acholeplasma laidlawii. For fluorescence labelling intact cells and isolated cell envelopes (membranes) from Salmonella typhimurium and Acholeplasma laidlawii were treated with mixed dansylchloride-lecithin-cholesterol vesicles. This kind of dansylation, which has been supposed to be specific for cell surface proteins, produced fluorescent protein pattern after SDS-polyacrylamide gel electrophoresis only when isolated envelopes were dansylated. Acid hydrolysis of fluorescent cell envelopes of Salmonella typhimurium yielded O-dansyltryosine and epsilon-N-dansyl-lysine besides the free sulfonic acid and unidentified compounds. However, no fluorescent proteins were detectable in cell envelopes isolated from dansylated intact bacteria from Salmonella typhimurium. In accord Acholeplasma laidlawii showed only fluorescence from proteins with a molecular weight higher than 100000."}
{"id": "PMID:235246", "title": "The metabolism of pyrimidines by proteolytic clostridia.", "content": "Uracil was used by growing cultures of Clostridium sporogenes, and by proteolytic strains of C. botulinum types A and B. Uracil was not used by C. bifermentans; C. botulinum, type B (non-proteolytic); C. botulinum, type F (non-proteolytic); C. botulinum, type E; C. butyricum; C. cochlearium; C. difficile; C. histolyticum; C. oedematiens, type A; C. paraputrificum; C. scatologenes; C. specticum; C. sordellii; C. sticklandii; C. tertium; C. tetani; C. tetanomorphum; C. welchii, types A, B, C, E and 4 untyped strains. The growth of C. sporogenes was not increased by uracil; it was reduced to dihydrouracil. Experiments with washed cells of C. sporogenes showed that the uracil-reducing system was inducible. Washed cell suspensions incubated under hydrogen with uracil, thymine, iso-barbituric acid, 5-amino uracil and cytosine consumed 1 mole H2/mole pyrimidine. The reduction product of cytosine was dihydrouracil indicating that it was deaminated before reduction. The reduction products of the  remaining pyrimidines were the corresponding dihydro derivatives. Extracts of C. sporogenes reduced uracil in the presence of NADPH2 but not NADH2.", "contents": "The metabolism of pyrimidines by proteolytic clostridia. Uracil was used by growing cultures of Clostridium sporogenes, and by proteolytic strains of C. botulinum types A and B. Uracil was not used by C. bifermentans; C. botulinum, type B (non-proteolytic); C. botulinum, type F (non-proteolytic); C. botulinum, type E; C. butyricum; C. cochlearium; C. difficile; C. histolyticum; C. oedematiens, type A; C. paraputrificum; C. scatologenes; C. specticum; C. sordellii; C. sticklandii; C. tertium; C. tetani; C. tetanomorphum; C. welchii, types A, B, C, E and 4 untyped strains. The growth of C. sporogenes was not increased by uracil; it was reduced to dihydrouracil. Experiments with washed cells of C. sporogenes showed that the uracil-reducing system was inducible. Washed cell suspensions incubated under hydrogen with uracil, thymine, iso-barbituric acid, 5-amino uracil and cytosine consumed 1 mole H2/mole pyrimidine. The reduction product of cytosine was dihydrouracil indicating that it was deaminated before reduction. The reduction products of the  remaining pyrimidines were the corresponding dihydro derivatives. Extracts of C. sporogenes reduced uracil in the presence of NADPH2 but not NADH2."}
{"id": "PMID:235247", "title": "Psychotropic drugs on general medical and surgical wards of a teaching hospital.", "content": "We examined the prescribing habits for psychotropic drugs of internists, surgeons, and gynecologists on their inpatient wards in a teaching hospital. Data were gathered from patients' charts and pharmacy records. In a six-week period, 9% of all admissions received such a drug. The male:female ratio and black:white ratios were studied; the maximum incidence of receiving these medications was in the 50- to 60-year age group. Minor tranquilizers were prescribed most frequently, followed, respectively, by major tranquilizers, barbiturates, and antidepressants. Less than half the available drugs were used, but drugs of differernt groups were often used interchangeably in an unsystematic fashion, and there was little evidence as to how effective a drug had been. It also seemed that depression was often overlooked or insufficiently treated.", "contents": "Psychotropic drugs on general medical and surgical wards of a teaching hospital. We examined the prescribing habits for psychotropic drugs of internists, surgeons, and gynecologists on their inpatient wards in a teaching hospital. Data were gathered from patients' charts and pharmacy records. In a six-week period, 9% of all admissions received such a drug. The male:female ratio and black:white ratios were studied; the maximum incidence of receiving these medications was in the 50- to 60-year age group. Minor tranquilizers were prescribed most frequently, followed, respectively, by major tranquilizers, barbiturates, and antidepressants. Less than half the available drugs were used, but drugs of differernt groups were often used interchangeably in an unsystematic fashion, and there was little evidence as to how effective a drug had been. It also seemed that depression was often overlooked or insufficiently treated."}
{"id": "PMID:235248", "title": "Psychotropic drug use in the Boston area. A report from the Boston Collaborative Drug Surveillance Program.", "content": "During 1972, adults admitted to general medical and surgical wards in Boston area hospitals were interviewed to determine their use of prescribed psychotropic drugs prior to hospitalization. Patients hospitalized for psychiatric disorders or psychogenic (\"functional\") disease were excluded. Patients who had taken prescribed drugs that could not be identified were considered nonusers. Of the total sample, 20% gave a histroy of psychotropic drug use. Antianxiety drugs were taken by 15% of the patients and accounted for two thirds of total psychotropic drug use. Hypnotics were taken by another 4% of the sample. Slightly over half of antianxiety and hypnotic drug use was for a year or more. Use was more frequent in patients with potentially chronic medical disorders. The findings, in general, are consistent with other studies employing other methods to investigate the use of psychotropic drugs. Simple studies of use, however, do not provide a sole or adequate definition of treatment option, need, or efficacy.", "contents": "Psychotropic drug use in the Boston area. A report from the Boston Collaborative Drug Surveillance Program. During 1972, adults admitted to general medical and surgical wards in Boston area hospitals were interviewed to determine their use of prescribed psychotropic drugs prior to hospitalization. Patients hospitalized for psychiatric disorders or psychogenic (\"functional\") disease were excluded. Patients who had taken prescribed drugs that could not be identified were considered nonusers. Of the total sample, 20% gave a histroy of psychotropic drug use. Antianxiety drugs were taken by 15% of the patients and accounted for two thirds of total psychotropic drug use. Hypnotics were taken by another 4% of the sample. Slightly over half of antianxiety and hypnotic drug use was for a year or more. Use was more frequent in patients with potentially chronic medical disorders. The findings, in general, are consistent with other studies employing other methods to investigate the use of psychotropic drugs. Simple studies of use, however, do not provide a sole or adequate definition of treatment option, need, or efficacy."}
{"id": "PMID:235249", "title": "Cyclic adenosine monophosphate in cerebral cortex. Alterations following trauma.", "content": "Stab-wound injury produced a seven-fold elevation in cyclic adenosine monophosphate (AMP) in mouse brain within one minute. The increase in cyclic AMP in the brain was blocked by prior treatment of the animal by theophylline, chlorpromazine, trifluoperazine hydrochloride, and diphenhydramine hydrochloride. Neither dichloroisoproterenol, pronetalol, nor reserpine blocked in the rise in cyclic AMP concentration due to injury. The results following administration of drugs suggest that the increases in cyclic AMP due to injury may be mediated by adenosine. Theophylline and phenothiazine derivatives have been shown previously to decrease adenosine-mediated increases in cyclic AMP in brain slices. The absence of any effect after administration of dichloroisoproterenol or pronetalol suggests that the increase in cyclic AMP after injury is not through catecholamine release. Hypothermia reduced the increase in cyclic AMP in injured brain after one minute.", "contents": "Cyclic adenosine monophosphate in cerebral cortex. Alterations following trauma. Stab-wound injury produced a seven-fold elevation in cyclic adenosine monophosphate (AMP) in mouse brain within one minute. The increase in cyclic AMP in the brain was blocked by prior treatment of the animal by theophylline, chlorpromazine, trifluoperazine hydrochloride, and diphenhydramine hydrochloride. Neither dichloroisoproterenol, pronetalol, nor reserpine blocked in the rise in cyclic AMP concentration due to injury. The results following administration of drugs suggest that the increases in cyclic AMP due to injury may be mediated by adenosine. Theophylline and phenothiazine derivatives have been shown previously to decrease adenosine-mediated increases in cyclic AMP in brain slices. The absence of any effect after administration of dichloroisoproterenol or pronetalol suggests that the increase in cyclic AMP after injury is not through catecholamine release. Hypothermia reduced the increase in cyclic AMP in injured brain after one minute."}
{"id": "PMID:235253", "title": "A psychological study of patients undergoing cosmetic surgery.", "content": "This is an investigative study of the personality of patients requesting cosmetic rhinoplasty. Analysis of data obtained from objective projective tests and psychological interviews indicated that patients seeking cosmetic surgery are not as psychologically disturbed as often as described. Comparative studies showed certain personality characteristics to be associated with patients who seek cosmetic surgery. While evaluations 18 months after surgery showed no major personality change, self-concept was improved. Certain disturbing personality patterns indicative of psychological risk were identified. These fell more in the range personality disorders, exemplified by the infantile-narcissistic and the manipulative controlling personalities rather than in somatic ranges. We recommend a simple interview question method of counseling designed to identify underlying psychological manifestations and to control the potential problem patient.", "contents": "A psychological study of patients undergoing cosmetic surgery. This is an investigative study of the personality of patients requesting cosmetic rhinoplasty. Analysis of data obtained from objective projective tests and psychological interviews indicated that patients seeking cosmetic surgery are not as psychologically disturbed as often as described. Comparative studies showed certain personality characteristics to be associated with patients who seek cosmetic surgery. While evaluations 18 months after surgery showed no major personality change, self-concept was improved. Certain disturbing personality patterns indicative of psychological risk were identified. These fell more in the range personality disorders, exemplified by the infantile-narcissistic and the manipulative controlling personalities rather than in somatic ranges. We recommend a simple interview question method of counseling designed to identify underlying psychological manifestations and to control the potential problem patient."}
{"id": "PMID:235254", "title": "Characteristics of three strains of avian adenoviruses isolated in Queensland. II. Biochemical, biophysical, and electron-microscope studies.", "content": "Three strains of adenovirus were relatively stable to the effects of chloroform, extreme pH, trypsin, heat, lyophilization, and ultrasonication. The structure of the viruses and their mode of replication in cell cultures confirmed these viruses to be members of the avian adenoviruses.", "contents": "Characteristics of three strains of avian adenoviruses isolated in Queensland. II. Biochemical, biophysical, and electron-microscope studies. Three strains of adenovirus were relatively stable to the effects of chloroform, extreme pH, trypsin, heat, lyophilization, and ultrasonication. The structure of the viruses and their mode of replication in cell cultures confirmed these viruses to be members of the avian adenoviruses."}
{"id": "PMID:235255", "title": "Coccidiosis and intestinal pH in chickens.", "content": "The intestinal contents of white Leghorn cockerels were significantly lower in pH in birds infected with Eimeria mivati, E. maxima, or E. necatrix than in uninoculated control birds. The particular Eimeria species used affected the region of the intestine involved, the days (5-9 postinoculation) on which pH decreased, and the magnitude of the decrease. The effects on the magnitude and frequency of pH decrease were as follows: E. mivati, marked in the duodenum and jejunum, variable in the ileum; E. maxima, slight in the duodenum, variable in the jejunum and ileum; E. necatrix, no change in the duodenum, variable in the jejunum and ileum. Infection with E. tenella did not change the intestinal pH. The pH of the gizzard was occasionally higher in birds infected with E. mivati or E. necatrix than in uninoculated control birds. With all four species, on some days the pH in the ceca was higher than in the ceca of controls. These results and previous reports indicate that infection with one of the above four species or with E. acervulina or E. brunetti produces the greatest and most consistent decrease in pH in the region of the intestine where the particular species characteristically produces the severest infection.", "contents": "Coccidiosis and intestinal pH in chickens. The intestinal contents of white Leghorn cockerels were significantly lower in pH in birds infected with Eimeria mivati, E. maxima, or E. necatrix than in uninoculated control birds. The particular Eimeria species used affected the region of the intestine involved, the days (5-9 postinoculation) on which pH decreased, and the magnitude of the decrease. The effects on the magnitude and frequency of pH decrease were as follows: E. mivati, marked in the duodenum and jejunum, variable in the ileum; E. maxima, slight in the duodenum, variable in the jejunum and ileum; E. necatrix, no change in the duodenum, variable in the jejunum and ileum. Infection with E. tenella did not change the intestinal pH. The pH of the gizzard was occasionally higher in birds infected with E. mivati or E. necatrix than in uninoculated control birds. With all four species, on some days the pH in the ceca was higher than in the ceca of controls. These results and previous reports indicate that infection with one of the above four species or with E. acervulina or E. brunetti produces the greatest and most consistent decrease in pH in the region of the intestine where the particular species characteristically produces the severest infection."}
{"id": "PMID:235268", "title": "[The effect of a dimenhydrinate combination of the cardiovascular system and cerebral blood circulation in the anaesthetized dog].", "content": "The influence of Vertigo-Vomex (VV) and Vertigo-Vomex Retard (VVR) on the perfusion rate of the a. carotis interna and on the peripheral circulation was tested in 30 anaesthetized dogs. These drugs represent beta-dimethylamino-ethyl-benzhydrylether-1,3-dimethyl-8-chloroxanthine (dimenhydrinate, Vomex A) with the addition of pyridine-3-carbonic acid (nicotinic acid, niacin) and pyridoxine-HCl (vitamin B6) and its retard preparation. A) Angiographic researches of the brain vessels after i.v. injection of VV. B) Perfusion rate in the a. carotis int. by electromagnetic flowmeter; measurements of blood pressure, heart rate, and acid-base balance; reactions after injection of niacin, dimenhydrinate, and pyridoxine-HCl as well as after a combination of both. C) Same measurements as in B but after oral application. In one out of four cases there was a dilation of the brain vessels, in two cases there was a small one, in one case there was none. Niacin induces a short-lasting augmentation of the perfusion rate in the a. carotis int. simultaneously with rising aortic blood pressure. Dimenhydrinate with pyridoxine-HCl slightly increases the heart rate. Combined with niacin the perfusion rate shortly increases immediately after injection of niacin without any rise of blood pressure but combined with a fall in blood pH and standard bicarbonate. After oral application of VVR there was a slight but not significant augmentation of the perfusion rate in the a. carotis int. combined with rising blood pressure but with no change of the blood pH. Therefore the certain intivertigineous effect of VV and VVR cannot be explained by a rise of the perfusion rate in the inner ear or in the brain. In view of our results the central effect of dimenhydrinate combined with niacin and pyridoxine-HCl hypothetically may be improved by metabolic influences on the cells and their membranes.", "contents": "[The effect of a dimenhydrinate combination of the cardiovascular system and cerebral blood circulation in the anaesthetized dog]. The influence of Vertigo-Vomex (VV) and Vertigo-Vomex Retard (VVR) on the perfusion rate of the a. carotis interna and on the peripheral circulation was tested in 30 anaesthetized dogs. These drugs represent beta-dimethylamino-ethyl-benzhydrylether-1,3-dimethyl-8-chloroxanthine (dimenhydrinate, Vomex A) with the addition of pyridine-3-carbonic acid (nicotinic acid, niacin) and pyridoxine-HCl (vitamin B6) and its retard preparation. A) Angiographic researches of the brain vessels after i.v. injection of VV. B) Perfusion rate in the a. carotis int. by electromagnetic flowmeter; measurements of blood pressure, heart rate, and acid-base balance; reactions after injection of niacin, dimenhydrinate, and pyridoxine-HCl as well as after a combination of both. C) Same measurements as in B but after oral application. In one out of four cases there was a dilation of the brain vessels, in two cases there was a small one, in one case there was none. Niacin induces a short-lasting augmentation of the perfusion rate in the a. carotis int. simultaneously with rising aortic blood pressure. Dimenhydrinate with pyridoxine-HCl slightly increases the heart rate. Combined with niacin the perfusion rate shortly increases immediately after injection of niacin without any rise of blood pressure but combined with a fall in blood pH and standard bicarbonate. After oral application of VVR there was a slight but not significant augmentation of the perfusion rate in the a. carotis int. combined with rising blood pressure but with no change of the blood pH. Therefore the certain intivertigineous effect of VV and VVR cannot be explained by a rise of the perfusion rate in the inner ear or in the brain. In view of our results the central effect of dimenhydrinate combined with niacin and pyridoxine-HCl hypothetically may be improved by metabolic influences on the cells and their membranes."}
{"id": "PMID:235269", "title": "The treatment of threatened premature labor by tocolytics, Ca++-Antagonists and anti-inflammatory drugs.", "content": "Prevention of premature labor is of considerable interest in research and clinics.  Three groups of pharmacological agents can inhibit uterine activity: tocolytics, spasmolytics, and anti-inflammatory drugs.  Tocolvtics like isoprenaline and fenoterol stimulate the beta-adrenergic receptors in decreasing the amplitude of contractions but with little effort on the muscle tone.  Spasmolytic uterine inhibitors produce primarily a decrease in contraction frequency and tonus, and finally in high concentrations a decrease of the amplitude of contraction.  An alteration of the electro-mechnaical coupling mechanism of the muscle cell via calcium antagonism is discussed.  A combined application of both drugs, tocolytics and spasmolvtics, potentiates the inhibitory effect and may simultaneously reduce undesirable systemic and cardiovascular side effects.  Anti-inflammatory agents of the acetylsalicylic acid or indometacin type reduce uterine activity by inhibition of prostaglandin synetheis and release.  They are clinically used as complementary agents in case of unsuccessful tocolytic or spasmolytic inhibition of uterine activity. In our study only 21.4 per cent out of 603 cases of threatened premature labor justified a tocolytic treatment.  Before attempting an inhibition one must decide on certain clinical parameters.", "contents": "The treatment of threatened premature labor by tocolytics, Ca++-Antagonists and anti-inflammatory drugs. Prevention of premature labor is of considerable interest in research and clinics.  Three groups of pharmacological agents can inhibit uterine activity: tocolytics, spasmolytics, and anti-inflammatory drugs.  Tocolvtics like isoprenaline and fenoterol stimulate the beta-adrenergic receptors in decreasing the amplitude of contractions but with little effort on the muscle tone.  Spasmolytic uterine inhibitors produce primarily a decrease in contraction frequency and tonus, and finally in high concentrations a decrease of the amplitude of contraction.  An alteration of the electro-mechnaical coupling mechanism of the muscle cell via calcium antagonism is discussed.  A combined application of both drugs, tocolytics and spasmolvtics, potentiates the inhibitory effect and may simultaneously reduce undesirable systemic and cardiovascular side effects.  Anti-inflammatory agents of the acetylsalicylic acid or indometacin type reduce uterine activity by inhibition of prostaglandin synetheis and release.  They are clinically used as complementary agents in case of unsuccessful tocolytic or spasmolytic inhibition of uterine activity. In our study only 21.4 per cent out of 603 cases of threatened premature labor justified a tocolytic treatment.  Before attempting an inhibition one must decide on certain clinical parameters."}
{"id": "PMID:235271", "title": "Calorimetric analysis of aspartate transcarbamylase from Escherichia coli: binding of cytosine 5'-triphosphate and adenosine 5'-triphosphate.", "content": "The binding of CTP and ATP to aspartate transcarbamylase at pH 7.8 and 8.5 at 25 degrees has been investigated by equilibrium dialysis and flow microcalorimetry. The binding isotherms for CTP at both pH 7.8 and 8.5 and ATP AT PH 8.5 can be fit by a model which assumes three tight, three moderately tight, and six weak binding sites. The binding isotherms for ATP at pH 7.8 are best fit by a model which assumes six tight and six weaker sites. Both finite differenceH binding and finite differenceS binding are negative for both nucleotides at both pH values, so that the binding is enthalpy driven. For both nucleotides, finite differenceH is the same for the first two classes of binding sites, implying that the difference in the dissociation constants of these two classes of sites is the result of entropic effects. Direct pH measurements and calorimetric measurements in two buffers with very different heats of ionization (Tris and Hepes) indicate that the binding of both nucleotides is accompanied by the binding of protons. In the pH range 6.7-8.4, the number of moles of protons bound per mole of nucleotide increases as the pH decreases.", "contents": "Calorimetric analysis of aspartate transcarbamylase from Escherichia coli: binding of cytosine 5'-triphosphate and adenosine 5'-triphosphate. The binding of CTP and ATP to aspartate transcarbamylase at pH 7.8 and 8.5 at 25 degrees has been investigated by equilibrium dialysis and flow microcalorimetry. The binding isotherms for CTP at both pH 7.8 and 8.5 and ATP AT PH 8.5 can be fit by a model which assumes three tight, three moderately tight, and six weak binding sites. The binding isotherms for ATP at pH 7.8 are best fit by a model which assumes six tight and six weaker sites. Both finite differenceH binding and finite differenceS binding are negative for both nucleotides at both pH values, so that the binding is enthalpy driven. For both nucleotides, finite differenceH is the same for the first two classes of binding sites, implying that the difference in the dissociation constants of these two classes of sites is the result of entropic effects. Direct pH measurements and calorimetric measurements in two buffers with very different heats of ionization (Tris and Hepes) indicate that the binding of both nucleotides is accompanied by the binding of protons. In the pH range 6.7-8.4, the number of moles of protons bound per mole of nucleotide increases as the pH decreases."}
{"id": "PMID:235272", "title": "Temperature and requency dependence of solvent proton relaxation rates in solutions of manganese(II) carbonic anhydrase.", "content": "Longitudinal and transverse proton relaxation rates of water in solutions of manganese(II) bovine carbonic anhydrase have been measured by pulsed nuclear magnetic resonance spectrometry as a function of temperature (2-35 degrees), frequently (5-100 MHz) and pH. The pH dependence of the longitudinal relaxation rate was fitted to a sigmoidal curve with a pK value at 7.8, while the esterase activity of the manganese(II) enzyme in the hydrolysis of p-nitrophenyl acetate revealed an inflection point at pK = 8.2. The hydration number of manganese(II) carbonic anhydrase could be derived using either the frequency dependence of T1p or the T1p/T2p ratio at only one (high) frequency. Both treatments are in agreement with a model in which one water molecule is bound to the metal at high pH. At low pH the relaxation data imply that no-H20 exists in the first coordination sphere of the manganese ion. The various parameters which are responsible for the proton relaxation mechanisms have been evaluated and are compared to other manganese(II) enzyme systems. The pH dependence of the binding constant of manganese to apocarbonic anhydrase is also reported.", "contents": "Temperature and requency dependence of solvent proton relaxation rates in solutions of manganese(II) carbonic anhydrase. Longitudinal and transverse proton relaxation rates of water in solutions of manganese(II) bovine carbonic anhydrase have been measured by pulsed nuclear magnetic resonance spectrometry as a function of temperature (2-35 degrees), frequently (5-100 MHz) and pH. The pH dependence of the longitudinal relaxation rate was fitted to a sigmoidal curve with a pK value at 7.8, while the esterase activity of the manganese(II) enzyme in the hydrolysis of p-nitrophenyl acetate revealed an inflection point at pK = 8.2. The hydration number of manganese(II) carbonic anhydrase could be derived using either the frequency dependence of T1p or the T1p/T2p ratio at only one (high) frequency. Both treatments are in agreement with a model in which one water molecule is bound to the metal at high pH. At low pH the relaxation data imply that no-H20 exists in the first coordination sphere of the manganese ion. The various parameters which are responsible for the proton relaxation mechanisms have been evaluated and are compared to other manganese(II) enzyme systems. The pH dependence of the binding constant of manganese to apocarbonic anhydrase is also reported."}
{"id": "PMID:235273", "title": "A study of subtilisin types Novo and Carlsberg by circular polarization of fluorescence.", "content": "The circular polarization of the luminescence of a chromophore, in addition to its circular dichroism and optical rotatory dispersion, is a manifestation of its asymmetry. In the study of proteins, the circular polarization of luminescence yields more specific information than circular dichroism or optical rotatory dispersion since nonfluorescent chromophores do not contribute, and the spectra of the tyrosine and the tryptophan residues are much better resolved in emission than in absorption. The circular polarization of the fluorescence of the tyrosine and tryptophan residues in derivatives of subtilisin Carlsberg and subtilisin Novo were indeed resolved in this study. The tyrosine residues in the Carlsberg protein, and both tyrosine and tryptophan residues in the Novo protein, were found to be heterogeneous with respect to their optical activity and emission spectra. Changes in the environment of the emitting tyrosine residues in both proteins and in the tryptophan residues in the Novo protein were found on changing the pH from 5.0 to 8.3. The pH dependence of the enzymatic activity of these proteins may thus be due, at least in part, to conformational changes in the molecules. Fluorescence circular polarization also revealed that covalently bound inhibitors at the active site of subtilisin Novo affect the environment of the emitting aromatic side chains, presumably via changes in conformation.", "contents": "A study of subtilisin types Novo and Carlsberg by circular polarization of fluorescence. The circular polarization of the luminescence of a chromophore, in addition to its circular dichroism and optical rotatory dispersion, is a manifestation of its asymmetry. In the study of proteins, the circular polarization of luminescence yields more specific information than circular dichroism or optical rotatory dispersion since nonfluorescent chromophores do not contribute, and the spectra of the tyrosine and the tryptophan residues are much better resolved in emission than in absorption. The circular polarization of the fluorescence of the tyrosine and tryptophan residues in derivatives of subtilisin Carlsberg and subtilisin Novo were indeed resolved in this study. The tyrosine residues in the Carlsberg protein, and both tyrosine and tryptophan residues in the Novo protein, were found to be heterogeneous with respect to their optical activity and emission spectra. Changes in the environment of the emitting tyrosine residues in both proteins and in the tryptophan residues in the Novo protein were found on changing the pH from 5.0 to 8.3. The pH dependence of the enzymatic activity of these proteins may thus be due, at least in part, to conformational changes in the molecules. Fluorescence circular polarization also revealed that covalently bound inhibitors at the active site of subtilisin Novo affect the environment of the emitting aromatic side chains, presumably via changes in conformation."}
{"id": "PMID:235274", "title": "Equilibrium of Bowman-Birk inhibitor association with trypsin and alpha-chymotrypsin.", "content": "Association constants, enthalpies, and stoichiometries of Bowman-Birk soybean inhibitor for trypsin and alpha-chymotrypsin were measured in the pH range 4-8 at 25 degrees, 0.01 M Ca2+. The results are quoted in terms of moles of protease active sites, from active site titration. Enthalpies were obtained from calorimetry. The inhibitor was modified by carboxyl group modification, and by tryptic and chymotryptic attack. Association thermodynamics and stoichiometries of the modified inhibitors with both proteases were also determined. There is one independent site for each protease on the inhibitor protein. Modification decreases association to some extent, but does not appear to change stoichiometry or protease binding site independency. In the pH 4 region the association enthalpies are endothermic, of the order 6 kcal/mol for both trypsin and chymotrypsin. With increasing pH, the enthalpies decrease and become exothermic at pH 8 for chymotrypsin. Positive entropies, 50 cal mol-1 deg-1, occur at pH 4-5. They decrease as pH increases, but are always positive in sign. The observed to accompany the overall reaction, such as H+ transfer steps. The enthalpies and entropies probably compensate over the pH range 4-8, with a characteristic temperature of 390 plus or minus 30 degrees K. Estimates were made of the macromolecular Coulomb charge products in inhibitor-protease interaction. These range from about +5 to -60, over pH range 4-8, depending on the protease. Although intermolecular Coulombic forces cannot be easily delineated at the specific side chain level, they may operate at the macromolecule level.", "contents": "Equilibrium of Bowman-Birk inhibitor association with trypsin and alpha-chymotrypsin. Association constants, enthalpies, and stoichiometries of Bowman-Birk soybean inhibitor for trypsin and alpha-chymotrypsin were measured in the pH range 4-8 at 25 degrees, 0.01 M Ca2+. The results are quoted in terms of moles of protease active sites, from active site titration. Enthalpies were obtained from calorimetry. The inhibitor was modified by carboxyl group modification, and by tryptic and chymotryptic attack. Association thermodynamics and stoichiometries of the modified inhibitors with both proteases were also determined. There is one independent site for each protease on the inhibitor protein. Modification decreases association to some extent, but does not appear to change stoichiometry or protease binding site independency. In the pH 4 region the association enthalpies are endothermic, of the order 6 kcal/mol for both trypsin and chymotrypsin. With increasing pH, the enthalpies decrease and become exothermic at pH 8 for chymotrypsin. Positive entropies, 50 cal mol-1 deg-1, occur at pH 4-5. They decrease as pH increases, but are always positive in sign. The observed to accompany the overall reaction, such as H+ transfer steps. The enthalpies and entropies probably compensate over the pH range 4-8, with a characteristic temperature of 390 plus or minus 30 degrees K. Estimates were made of the macromolecular Coulomb charge products in inhibitor-protease interaction. These range from about +5 to -60, over pH range 4-8, depending on the protease. Although intermolecular Coulombic forces cannot be easily delineated at the specific side chain level, they may operate at the macromolecule level."}
{"id": "PMID:235275", "title": "Hydrogen exchange in nucleosides and nucleotides. Measurement of hydrogen exchange by stopped-flow and ultraviolet difference spectroscopy.", "content": "Time-dependent changes in the ultraviolet absorbance of the adenine chromophore are observed in the stopped-flow spectrophotometer when adenosine and its analogs are rapidly transferred from protium oxide to deuterium oxide. These absorbance changes are shown to result from hydrogen exchange in the exocyclic amino groups of the purine ribonucleosides by using derivatives of adenosine in which methyl groups replace exchangeable hydrogens and by showing that the general characteristics of hydrogen exchange in adenosine analogs agree with those found here. A study of the dependence of hydrogen-exchange rate constants on adenosine, AMP, and phosphate concentration showed there is a second-order dependence on AMP concentration which is primarily due to intermolecular catalysis by the phosphate group of the nucleotide. The deuterium oxide perturbation difference spectrum, obtained at equilibrium, was found to contain two components that result from blue shifts of the adenine chromophore absorbance: (1) a shift cause by the substitution of deuterium for protium in the ring (N1) nitrogen and exocyclic nitrogens, and (2) a shift associated with a change in the polarizability of the medium. Since the theory of solvent perturbation, which is used to measure the relative \"exposure\" of chromophores in macromolecules, assumes that the spectral shifts observed are solely due to (2) above, the use of deuterium oxide as a measure of chromophore exposure to perturbants the size of water must be reexamined.", "contents": "Hydrogen exchange in nucleosides and nucleotides. Measurement of hydrogen exchange by stopped-flow and ultraviolet difference spectroscopy. Time-dependent changes in the ultraviolet absorbance of the adenine chromophore are observed in the stopped-flow spectrophotometer when adenosine and its analogs are rapidly transferred from protium oxide to deuterium oxide. These absorbance changes are shown to result from hydrogen exchange in the exocyclic amino groups of the purine ribonucleosides by using derivatives of adenosine in which methyl groups replace exchangeable hydrogens and by showing that the general characteristics of hydrogen exchange in adenosine analogs agree with those found here. A study of the dependence of hydrogen-exchange rate constants on adenosine, AMP, and phosphate concentration showed there is a second-order dependence on AMP concentration which is primarily due to intermolecular catalysis by the phosphate group of the nucleotide. The deuterium oxide perturbation difference spectrum, obtained at equilibrium, was found to contain two components that result from blue shifts of the adenine chromophore absorbance: (1) a shift cause by the substitution of deuterium for protium in the ring (N1) nitrogen and exocyclic nitrogens, and (2) a shift associated with a change in the polarizability of the medium. Since the theory of solvent perturbation, which is used to measure the relative \"exposure\" of chromophores in macromolecules, assumes that the spectral shifts observed are solely due to (2) above, the use of deuterium oxide as a measure of chromophore exposure to perturbants the size of water must be reexamined."}
{"id": "PMID:235276", "title": "A multienzyme complex for CO2 fixation.", "content": "Acetyl-coenzyme A carboxylase from Euglena gracilis strain Z was isolated as a component of a multienzyme complex which includes phosphoenolpyruvate carboxylase and malate dehydrogenase. The multienzyme complex was shown to exist in crude extracts and was purified to a homogeneous protein with a molecular weight of 360,000 by gel filtration. The ratio of the activities of the constituent enzymes was acetyl-CoA carboxylase:phosphoenolpyruvate carboxylase:malate dehydrogenase, 1:25:500. The complex is proposed to operate in conjunction with malic enzyme, which is present in Euglena, to facilitate the formation of substrates, malonyl-CoA, and NADPH, for fatty acid biosynthesis. The interaction of the enzymes may represent a means of control of acetyl-CoA carboxylase activity in organisms which do not possess an enzyme subject to allosteric regulation. The acetyl-CoA carboxylase activity from Euglena is unaffected by citrate and isocitrate.", "contents": "A multienzyme complex for CO2 fixation. Acetyl-coenzyme A carboxylase from Euglena gracilis strain Z was isolated as a component of a multienzyme complex which includes phosphoenolpyruvate carboxylase and malate dehydrogenase. The multienzyme complex was shown to exist in crude extracts and was purified to a homogeneous protein with a molecular weight of 360,000 by gel filtration. The ratio of the activities of the constituent enzymes was acetyl-CoA carboxylase:phosphoenolpyruvate carboxylase:malate dehydrogenase, 1:25:500. The complex is proposed to operate in conjunction with malic enzyme, which is present in Euglena, to facilitate the formation of substrates, malonyl-CoA, and NADPH, for fatty acid biosynthesis. The interaction of the enzymes may represent a means of control of acetyl-CoA carboxylase activity in organisms which do not possess an enzyme subject to allosteric regulation. The acetyl-CoA carboxylase activity from Euglena is unaffected by citrate and isocitrate."}
{"id": "PMID:235277", "title": "Dissociation and characterization of enzymes from a multienzyme complex involved in CO2 fixation.", "content": "A multienzyme complex from Euglena, molecular weight about 360,000, containing phosphoenolpyruvate carboxylase, malate dehydrogenase, and acetyl-coenzyme A carboxylase has been dissociated into active constituent enzymes. The respective molecular weights are 183,000, 67,000, and 127,000. The malate dehydrogenase contained in the complex is electrophoretically distinct from other malate dehydrogenase isozymes found in Euglena. The K-m for HCO3minus of the free and complexed acetyl-CoA carboxylase is 4.2-5.4 mM, and the substrate dependency for acetyl-CoA describes a sigmoidal relationship. The HCO3minus K-m for the free phosphoenolpyruvate carboxylase is 7.3-5.4 mM while that for the same enzyme contained in the complex is 0.7-1.3 mM. Both the free and complexed forms ofphosphoenolpyruvate carboxylase have a K-m for phosphoenolpyruvate of 0.9-1.7 mM. The latter enzyme in both the complex and free forms is stimulated by NADH, acetyl-CoA, and ATP. In the free phosphoenolpyruvate carboxylase, the stimulation passes through a maximum depending on effector concentration. The effect of NADH is to increase V-max while K-m values remain unmodified.", "contents": "Dissociation and characterization of enzymes from a multienzyme complex involved in CO2 fixation. A multienzyme complex from Euglena, molecular weight about 360,000, containing phosphoenolpyruvate carboxylase, malate dehydrogenase, and acetyl-coenzyme A carboxylase has been dissociated into active constituent enzymes. The respective molecular weights are 183,000, 67,000, and 127,000. The malate dehydrogenase contained in the complex is electrophoretically distinct from other malate dehydrogenase isozymes found in Euglena. The K-m for HCO3minus of the free and complexed acetyl-CoA carboxylase is 4.2-5.4 mM, and the substrate dependency for acetyl-CoA describes a sigmoidal relationship. The HCO3minus K-m for the free phosphoenolpyruvate carboxylase is 7.3-5.4 mM while that for the same enzyme contained in the complex is 0.7-1.3 mM. Both the free and complexed forms ofphosphoenolpyruvate carboxylase have a K-m for phosphoenolpyruvate of 0.9-1.7 mM. The latter enzyme in both the complex and free forms is stimulated by NADH, acetyl-CoA, and ATP. In the free phosphoenolpyruvate carboxylase, the stimulation passes through a maximum depending on effector concentration. The effect of NADH is to increase V-max while K-m values remain unmodified."}
{"id": "PMID:235278", "title": "Effect of pH on the liver alcohol dehydrogenase reaction.", "content": "New transient kinetic methods, which allow kinetics to be carried out under conditions of excess substrate, have been employed to investigate the kinetics of hydride transfer from NADH to aromatic aldehydes and from aromatic alcohols to NAD+ as a function of pH. The hydride transfer rate from 4-deuterio-NADH to beta-naphthaldehyde is nearly pH independent from pH 6.0 to pH 9.9; the isotope effect is also pH independent with kappa-H/kappaD congruent to 2.3. Likewise, the rate of oxidation of benzyl alcohol by NAD+ changes little with pH between pH 8.75 and pH 5.9; the isotope effect for this process is between 3.0 and 4.4. Earlier substituent effect studies on the reduction of aromatic aldehydes were consistent with electrophilic catalysis by either zinc or a protonic acid. The pH independence of hydride transfer is consistent with electrophilic catalysis by zinc since such catalysis by protonic acid (with a pK between 6.0 and 10.0) would show strong pH dependence. However, protonic acid catalysis cannot be excluded if the pKa of the acid catalyst in the ternary NADH-E-RCOH complex were smaller than 6.0 or smaller than 10.0. The two kinetic parameters changing significantly with pH are the kinetic binding constant for ternary complex formation with aromatic alcohol and the rate of dissociation of aromatic alcohols from enzyme. This is consistent with base-catalyzed removal of a proton from alcohol substrated and consequent acid catalysis of protonation of a zinc-alcoholate complex. The equilibrium constant for hydride transfer from benzaldehyde to benzyl alcohol at pH 8.75 is K-eq equals kappa-H/kappa-H equals 42; this constant has important consequences concerning subunit interactions during liver alcohol dehydrogenase catalysis.", "contents": "Effect of pH on the liver alcohol dehydrogenase reaction. New transient kinetic methods, which allow kinetics to be carried out under conditions of excess substrate, have been employed to investigate the kinetics of hydride transfer from NADH to aromatic aldehydes and from aromatic alcohols to NAD+ as a function of pH. The hydride transfer rate from 4-deuterio-NADH to beta-naphthaldehyde is nearly pH independent from pH 6.0 to pH 9.9; the isotope effect is also pH independent with kappa-H/kappaD congruent to 2.3. Likewise, the rate of oxidation of benzyl alcohol by NAD+ changes little with pH between pH 8.75 and pH 5.9; the isotope effect for this process is between 3.0 and 4.4. Earlier substituent effect studies on the reduction of aromatic aldehydes were consistent with electrophilic catalysis by either zinc or a protonic acid. The pH independence of hydride transfer is consistent with electrophilic catalysis by zinc since such catalysis by protonic acid (with a pK between 6.0 and 10.0) would show strong pH dependence. However, protonic acid catalysis cannot be excluded if the pKa of the acid catalyst in the ternary NADH-E-RCOH complex were smaller than 6.0 or smaller than 10.0. The two kinetic parameters changing significantly with pH are the kinetic binding constant for ternary complex formation with aromatic alcohol and the rate of dissociation of aromatic alcohols from enzyme. This is consistent with base-catalyzed removal of a proton from alcohol substrated and consequent acid catalysis of protonation of a zinc-alcoholate complex. The equilibrium constant for hydride transfer from benzaldehyde to benzyl alcohol at pH 8.75 is K-eq equals kappa-H/kappa-H equals 42; this constant has important consequences concerning subunit interactions during liver alcohol dehydrogenase catalysis."}
{"id": "PMID:235279", "title": "19F nuclear magnetic resonance studies of structure and function relationships in trifluoroacetonylated rabbit muscle glyceraldehyde-3-phosphate dehydrogenase.", "content": "Specific reaction of Cys-149 with 3,3,3-trifluorobromacetone allows one to probe symmetry relation between the active center regions of tetrameric glyceraldehyde-3-phosphate dehydrogenase by 19F nuclear magnetic resonance (nmr) techniques. Nmr titration studies in the pH range of greatest enzymic activity reveal the existence of species with an (alphaalpha')2 structure; this symmetry is not induced by the coenzyme. Addition of NADH to the ketone-labeled protein causes the enzymic reduction of the ligand in a stereospecific manner and is used to demonstrate the functionality of residues other than Cys-149 that are essential for catalysis. The interpretation of chemical shift characteristics found for the trifluoroacetonyl group together with the kinetics of its reduction allows the derivation of a dynamic model for the enzymic structure which may contribute to understanding of the half-of-the-sites phenomenon.", "contents": "19F nuclear magnetic resonance studies of structure and function relationships in trifluoroacetonylated rabbit muscle glyceraldehyde-3-phosphate dehydrogenase. Specific reaction of Cys-149 with 3,3,3-trifluorobromacetone allows one to probe symmetry relation between the active center regions of tetrameric glyceraldehyde-3-phosphate dehydrogenase by 19F nuclear magnetic resonance (nmr) techniques. Nmr titration studies in the pH range of greatest enzymic activity reveal the existence of species with an (alphaalpha')2 structure; this symmetry is not induced by the coenzyme. Addition of NADH to the ketone-labeled protein causes the enzymic reduction of the ligand in a stereospecific manner and is used to demonstrate the functionality of residues other than Cys-149 that are essential for catalysis. The interpretation of chemical shift characteristics found for the trifluoroacetonyl group together with the kinetics of its reduction allows the derivation of a dynamic model for the enzymic structure which may contribute to understanding of the half-of-the-sites phenomenon."}
{"id": "PMID:235280", "title": "Enzymic and physicochemical properties of Streptomyces griseus trypsin.", "content": "Streptomyces griseus trypsin has been isolated from Pronase by ion-exchange chromatography on CM-Sephadex and SE-Sephadex. The isolated enzyme was homogeneous by the criteria tested except for a low degree of contamination by an enzyme with nontryptic activity. The latter could be partially resolved by chromatography on Bio-Rex 70. The molar absorbancy at 280 nm was found to be 3.96 times 10-4 M-1/cm and the E1cm1% was found to be 17.3. The molecular weight was 22,800 plus or minus 800. The enzyme was found to be stable at 0 degrees from pH 2 to 10. At 30 degrees the enzyme was maximally stable at pH 3-4 and significantly stabilized in the neutral and alkaline range by 15 mM Ca2+. Some evidence was obtained for a reversible denaturation of the enzyme at pH 12.0 and 2.0. The K-m for N-alpha-benzoyl-L-arginine ethyl ester at pH 8.0 in 20 mM CaCl2-0.1 M KCl-10 mM Tris-HCl buffer at 30 degrees was found to be 7.7 plus or minus 1.9 times 10-6 M and the esterase activity was observed to be dependent on an ionizing group with pK-a equals 5.85. In 2H2O this pKa was increased to 6.35 and the rate of hydrolysis dicreased threefold. The rate of hydrolysis was independent of pH between 8 and 10. The inhibition of the enzyme with L-1-chloro-3-tosylamido-4-phenyl-2-butanone was shown to be associated with the alkylation of its single histidine residue. This residue is present in a homologous amino acid sequence as the active-site histidine in trypsin and chymotrypsin. Optical rotatory dispersion and circular dichroism measurements over the pH range 5.3-10.5 indicated no significant conformational change until the pH was increased above 10.1. The observation that, under the conditions tested, acetylation and carbamylation of the NH2-terminal valine were incomplete is consistent with the view that this group is buried as an ion pair and only becomes available for deprotonation and reaction upon denaturation of the enzyme at pH values greater than 10.0.", "contents": "Enzymic and physicochemical properties of Streptomyces griseus trypsin. Streptomyces griseus trypsin has been isolated from Pronase by ion-exchange chromatography on CM-Sephadex and SE-Sephadex. The isolated enzyme was homogeneous by the criteria tested except for a low degree of contamination by an enzyme with nontryptic activity. The latter could be partially resolved by chromatography on Bio-Rex 70. The molar absorbancy at 280 nm was found to be 3.96 times 10-4 M-1/cm and the E1cm1% was found to be 17.3. The molecular weight was 22,800 plus or minus 800. The enzyme was found to be stable at 0 degrees from pH 2 to 10. At 30 degrees the enzyme was maximally stable at pH 3-4 and significantly stabilized in the neutral and alkaline range by 15 mM Ca2+. Some evidence was obtained for a reversible denaturation of the enzyme at pH 12.0 and 2.0. The K-m for N-alpha-benzoyl-L-arginine ethyl ester at pH 8.0 in 20 mM CaCl2-0.1 M KCl-10 mM Tris-HCl buffer at 30 degrees was found to be 7.7 plus or minus 1.9 times 10-6 M and the esterase activity was observed to be dependent on an ionizing group with pK-a equals 5.85. In 2H2O this pKa was increased to 6.35 and the rate of hydrolysis dicreased threefold. The rate of hydrolysis was independent of pH between 8 and 10. The inhibition of the enzyme with L-1-chloro-3-tosylamido-4-phenyl-2-butanone was shown to be associated with the alkylation of its single histidine residue. This residue is present in a homologous amino acid sequence as the active-site histidine in trypsin and chymotrypsin. Optical rotatory dispersion and circular dichroism measurements over the pH range 5.3-10.5 indicated no significant conformational change until the pH was increased above 10.1. The observation that, under the conditions tested, acetylation and carbamylation of the NH2-terminal valine were incomplete is consistent with the view that this group is buried as an ion pair and only becomes available for deprotonation and reaction upon denaturation of the enzyme at pH values greater than 10.0."}
{"id": "PMID:235281", "title": "Nuclear magnetic resonance studies of histone IV solution conformation.", "content": "The 220-MHz high-resolution proton magnetic resonance (PMR) spectrum of histone IV has been examined as a function of histone concentration, salt concentration, and pD. The hydrophobic C-terminal portion of the histone IV monomer appears to be largely PMR \"invisible\" indicating that this region of the polypeptide contains rigid secondary structure. Further loss of PMR resonance areas with increased histone IV concentration in neat D2O has been attributed to self-aggregation involving a monomer-dimer equilibrium. An equilibrium between the monomer and large aggregates, on the other hand, appears to dominate at NaCl concentrations above 0.01 M. pD studies reveal an abrupt increase in histone IV aggregation at pD smaller than 0.8 and precipitation of histone IV at pD values in the neighborhood of its isoelectric point, pD similar to 11.", "contents": "Nuclear magnetic resonance studies of histone IV solution conformation. The 220-MHz high-resolution proton magnetic resonance (PMR) spectrum of histone IV has been examined as a function of histone concentration, salt concentration, and pD. The hydrophobic C-terminal portion of the histone IV monomer appears to be largely PMR \"invisible\" indicating that this region of the polypeptide contains rigid secondary structure. Further loss of PMR resonance areas with increased histone IV concentration in neat D2O has been attributed to self-aggregation involving a monomer-dimer equilibrium. An equilibrium between the monomer and large aggregates, on the other hand, appears to dominate at NaCl concentrations above 0.01 M. pD studies reveal an abrupt increase in histone IV aggregation at pD smaller than 0.8 and precipitation of histone IV at pD values in the neighborhood of its isoelectric point, pD similar to 11."}
{"id": "PMID:235282", "title": "Surface properties of monomolecular films of oxidized and reduced cytochrome c and f.", "content": "The surface properties of monomolecular films of oxidized and reduced cytochromes f and c were measured at an air-water interface. Area/molecular (A) and surface potential (deltaV) for oxidized and reduced forms of the cytochromes were measured as a function of pH. Oxidized cyt f has a maximum for both A and deltaV at pH 7.5. At a surface pressure of 6 dyn/cm the maximum A equals 2600 plus or minus 50 A2 and the maximum deltaV equals 200 plus or minus 10 mV. Reduced cyt f as a function of pH has a minimum value for both A (2200 A2) and deltaV (95 mV). Oxidized cyt c as a function of pH has minima for A (140 A2) and deltaV (188 mV) at pH 7.0 and 7.3, respectively. On the other hand, reduced cyt has maximum values for A (220 A2) and deltaV (260 mV) at pH 7.0 and 7.3, respectively.", "contents": "Surface properties of monomolecular films of oxidized and reduced cytochrome c and f. The surface properties of monomolecular films of oxidized and reduced cytochromes f and c were measured at an air-water interface. Area/molecular (A) and surface potential (deltaV) for oxidized and reduced forms of the cytochromes were measured as a function of pH. Oxidized cyt f has a maximum for both A and deltaV at pH 7.5. At a surface pressure of 6 dyn/cm the maximum A equals 2600 plus or minus 50 A2 and the maximum deltaV equals 200 plus or minus 10 mV. Reduced cyt f as a function of pH has a minimum value for both A (2200 A2) and deltaV (95 mV). Oxidized cyt c as a function of pH has minima for A (140 A2) and deltaV (188 mV) at pH 7.0 and 7.3, respectively. On the other hand, reduced cyt has maximum values for A (220 A2) and deltaV (260 mV) at pH 7.0 and 7.3, respectively."}
{"id": "PMID:235283", "title": "The buoyant titration of native and carbamylated bovine serum mercaptalbumin.", "content": "The buoyant density titration curves of native and carbamylated bovine serum mercaptalbumin were measured throughout the pH range 5.3-12.7. Large increments in the buoyant density were observed above pH 10, with inflection pH values of 11.2 and 11.4 for native and carbamylated bovine serum mercaptalbumin, respectively. For the modified protein in which 25 out of 58 lysine residues were carbamylated, the buoyant densities were 0.048 g/ml higher at neutral pH and 0.024 g/ml higher at the extrapolated pH 13. The carbamyl groups apparently produce a larger residual density at pH 13 than they did in the case of ovalbumin. Homopolymer buoyant density titration data were demonstrated to be of value in calculating the contributions of titratable residues to the buoyant density of both proteins. The buoyant density increment at high pH was due largely to the deprotonation of the lysines as indicated by the diminished change in buoyant density between pH 10 and 12.7 for the modified protein. These density changes were attributable primarily to a gain of cesium ions. The limited modification of the lysine residues under mild reaction conditions and the rather high intrinsic dissociation constant of tyrosine residues in mercaptalbumin may indicate a preferential modification of easily accessible lysine residues. Phenolic deprotonation is facilitated by the neutralization of normally charged lysine residues and demonstrates ionic interactions between internal lysines and certain carboxyl and tyrosine residues thereby stabilizing the native state of the protein.", "contents": "The buoyant titration of native and carbamylated bovine serum mercaptalbumin. The buoyant density titration curves of native and carbamylated bovine serum mercaptalbumin were measured throughout the pH range 5.3-12.7. Large increments in the buoyant density were observed above pH 10, with inflection pH values of 11.2 and 11.4 for native and carbamylated bovine serum mercaptalbumin, respectively. For the modified protein in which 25 out of 58 lysine residues were carbamylated, the buoyant densities were 0.048 g/ml higher at neutral pH and 0.024 g/ml higher at the extrapolated pH 13. The carbamyl groups apparently produce a larger residual density at pH 13 than they did in the case of ovalbumin. Homopolymer buoyant density titration data were demonstrated to be of value in calculating the contributions of titratable residues to the buoyant density of both proteins. The buoyant density increment at high pH was due largely to the deprotonation of the lysines as indicated by the diminished change in buoyant density between pH 10 and 12.7 for the modified protein. These density changes were attributable primarily to a gain of cesium ions. The limited modification of the lysine residues under mild reaction conditions and the rather high intrinsic dissociation constant of tyrosine residues in mercaptalbumin may indicate a preferential modification of easily accessible lysine residues. Phenolic deprotonation is facilitated by the neutralization of normally charged lysine residues and demonstrates ionic interactions between internal lysines and certain carboxyl and tyrosine residues thereby stabilizing the native state of the protein."}
{"id": "PMID:235284", "title": "Kinetics and specificity of T4 polynucleotide kinase.", "content": "The kinetics of T4 polynucleotide kinase has been investigated at pH 8.0 and 37 degrees. Double reciprocal plots of initial rates vs. substrate concentrations as well as product inhibition studies have indicated that the enzyme reacts according to the ordered sequential mechanism shown in eq 2 in the text for phosphorylation of a DNA molecule. Based on this mechanism the rate equation for the overall reaction was deduced and the various kinetic constants estimated. Hill plots indicated little or no interaction between active sites in the enzyme. The apparent Michaelis constants and V-max were determined at a fixed ATP concentration, 66 muM, for a number of different substrates varying in chain length, base composition, and nature of the sugar, and a wide variation was found. For the nucleoside 3'-monophosphates tested both the apparent Michaelis constant and V-max values were from approximately 2 to 5 times larger than for the corresponding oligonucleotide. The following orders were obtained with regard to apparent Michaelis constants and V-max for the nucleoside 3'-monophosphates investigated: Michaelis constant, rGP greater than rUp greater than rCp greater than rAp greater than dTp; V-max, rGp greater than rCp greater than rAp greater than dTp greater than rUp. Somewhat similar results were also obtained with the deoxyoligonucleotides tested.", "contents": "Kinetics and specificity of T4 polynucleotide kinase. The kinetics of T4 polynucleotide kinase has been investigated at pH 8.0 and 37 degrees. Double reciprocal plots of initial rates vs. substrate concentrations as well as product inhibition studies have indicated that the enzyme reacts according to the ordered sequential mechanism shown in eq 2 in the text for phosphorylation of a DNA molecule. Based on this mechanism the rate equation for the overall reaction was deduced and the various kinetic constants estimated. Hill plots indicated little or no interaction between active sites in the enzyme. The apparent Michaelis constants and V-max were determined at a fixed ATP concentration, 66 muM, for a number of different substrates varying in chain length, base composition, and nature of the sugar, and a wide variation was found. For the nucleoside 3'-monophosphates tested both the apparent Michaelis constant and V-max values were from approximately 2 to 5 times larger than for the corresponding oligonucleotide. The following orders were obtained with regard to apparent Michaelis constants and V-max for the nucleoside 3'-monophosphates investigated: Michaelis constant, rGP greater than rUp greater than rCp greater than rAp greater than dTp; V-max, rGp greater than rCp greater than rAp greater than dTp greater than rUp. Somewhat similar results were also obtained with the deoxyoligonucleotides tested."}
{"id": "PMID:235285", "title": "Formaldehyde as a probe of DNA structure. I. Reaction with exocyclic amino groups of DNA bases.", "content": "A comprehensive description is given of both the equilibrium and the kinetic aspects of the reaction of formaldehyde with the exocyclic amino groups of derivatives of adenine, cytosine, and guanine; the results extend previous data in the literature to the point where formaldehyde can now be used as a quantitative probe of DNA structure and dynamic behavior. The main results are: (i) the reaction product is proven (by isolation followed by nuclear magnetic resonance (NMR) spectroscopy) to be a hydroxymethyl group; (ii) a dihydroxymethyl adduct is shown to exist at high formaldehyde concentrations; (iii) equilibrium constants at 25 degrees for forming the monoadduct with adenine and cytosine compounds are about 12 (M-1), while those for forming the dihydroxymethyl adduct are about 0.4 (M-1); (iv) the standard enthalpies for forming the monoadducts with adenine and cytosine compounds are about minus 4 to minus 6 kcal/mol; (v) indirect evidence is presented suggesting that a monohydroxymethyl group on adenine or cytosine derivatives exists preferentially as that rotational isomer which blocks Watson-Crick hydrogen bonding; (vi) in derivatives of guanine, it is shown that the N-1 endocyclic imino group can react with formaldehyde, as well as the amino group, the overall equilibrium constant being about 6 (M-1); (vii) all rate constants are reported, as well as their response to temperature, pH, and various solvent additives known to perturb DNA structure; (viii) using a series of substituted anilines, a linear free energy relation is obtained between the logarithm of both the forward and the reverse rate constant for the formaldehyde reaction and the amine pK, over a range of 10-8 change in amie basicity; (ix) using this relation, the pK's for protonating the nucleoside amino groups are estimated to lie in the range of minus 2 to minus 4; (x) a reaction mechanism is proposed; and (xi) some implications of these results forpolynucleotide studies are discussed.", "contents": "Formaldehyde as a probe of DNA structure. I. Reaction with exocyclic amino groups of DNA bases. A comprehensive description is given of both the equilibrium and the kinetic aspects of the reaction of formaldehyde with the exocyclic amino groups of derivatives of adenine, cytosine, and guanine; the results extend previous data in the literature to the point where formaldehyde can now be used as a quantitative probe of DNA structure and dynamic behavior. The main results are: (i) the reaction product is proven (by isolation followed by nuclear magnetic resonance (NMR) spectroscopy) to be a hydroxymethyl group; (ii) a dihydroxymethyl adduct is shown to exist at high formaldehyde concentrations; (iii) equilibrium constants at 25 degrees for forming the monoadduct with adenine and cytosine compounds are about 12 (M-1), while those for forming the dihydroxymethyl adduct are about 0.4 (M-1); (iv) the standard enthalpies for forming the monoadducts with adenine and cytosine compounds are about minus 4 to minus 6 kcal/mol; (v) indirect evidence is presented suggesting that a monohydroxymethyl group on adenine or cytosine derivatives exists preferentially as that rotational isomer which blocks Watson-Crick hydrogen bonding; (vi) in derivatives of guanine, it is shown that the N-1 endocyclic imino group can react with formaldehyde, as well as the amino group, the overall equilibrium constant being about 6 (M-1); (vii) all rate constants are reported, as well as their response to temperature, pH, and various solvent additives known to perturb DNA structure; (viii) using a series of substituted anilines, a linear free energy relation is obtained between the logarithm of both the forward and the reverse rate constant for the formaldehyde reaction and the amine pK, over a range of 10-8 change in amie basicity; (ix) using this relation, the pK's for protonating the nucleoside amino groups are estimated to lie in the range of minus 2 to minus 4; (x) a reaction mechanism is proposed; and (xi) some implications of these results forpolynucleotide studies are discussed."}
{"id": "PMID:235286", "title": "Formaldehyde as a probe of DNA structure. II. Reaction with endocyclic imino groups of DNA bases.", "content": "We describe the equilibrium and kinetic aspects of the formaldehyde reaction with the endocyclic imino groups of derivatives of thymine, uracil, and a series of halogenated uracils, as well as poly(uridylic acid) and poly(inosinic acid). The main results are: (i) the equilibrium constants for forming a hydroxymethyl adduct remain quite constant at about 2-2.5 (M-1) for all the compounds studied, independent of their pK; (ii) both forward and reverse rate constants with 5'-TMP are specific base catalyzed in the pH range of about 4-9; (iii) the response of the rate constants to temperature and to several solvent additives are measured; (iv) at neutral pH, for the series of pyrimidine compounds, a linear free energy relation is observed between the logarithm of both the forward and the reverse rate constant and the pK for deprotonation; (v) the unstructured polynucleotides, poly(U) and poly(I) react very similarly to their constituent monomers; (vi) a reaction mechanism is proposed; and (vii) some implications for polynucleotide studies are discussed. In an appendix, a method of spectral analysis is derived to obtain accurate estimates of the quite small equilibrium constants; this should be applicable to all similar two-component systems in which the final product is unobtainable, either by isolation or by saturation. Together with the results of the previous paper on the formaldehyde reaction with exocyclic amino groups (J. D. McGhee and P. H. von Hippel, preceding paper), these results form a reasonably comprehensive account of the basic chemical controls required to use formaldehyde as a quantitative probe of DNA structure.", "contents": "Formaldehyde as a probe of DNA structure. II. Reaction with endocyclic imino groups of DNA bases. We describe the equilibrium and kinetic aspects of the formaldehyde reaction with the endocyclic imino groups of derivatives of thymine, uracil, and a series of halogenated uracils, as well as poly(uridylic acid) and poly(inosinic acid). The main results are: (i) the equilibrium constants for forming a hydroxymethyl adduct remain quite constant at about 2-2.5 (M-1) for all the compounds studied, independent of their pK; (ii) both forward and reverse rate constants with 5'-TMP are specific base catalyzed in the pH range of about 4-9; (iii) the response of the rate constants to temperature and to several solvent additives are measured; (iv) at neutral pH, for the series of pyrimidine compounds, a linear free energy relation is observed between the logarithm of both the forward and the reverse rate constant and the pK for deprotonation; (v) the unstructured polynucleotides, poly(U) and poly(I) react very similarly to their constituent monomers; (vi) a reaction mechanism is proposed; and (vii) some implications for polynucleotide studies are discussed. In an appendix, a method of spectral analysis is derived to obtain accurate estimates of the quite small equilibrium constants; this should be applicable to all similar two-component systems in which the final product is unobtainable, either by isolation or by saturation. Together with the results of the previous paper on the formaldehyde reaction with exocyclic amino groups (J. D. McGhee and P. H. von Hippel, preceding paper), these results form a reasonably comprehensive account of the basic chemical controls required to use formaldehyde as a quantitative probe of DNA structure."}
{"id": "PMID:235288", "title": "The binding of hemoglobin to membranes of normal and sickle erythrocytes.", "content": "The binding of hemoglobins A, S, and A2 to red cell membranes prepared by hypotonic lysis from normal blood and blood from persons with sickle cell anemia was quantified under a variety of conditions using hemoglobin labelled by alkylation with 14C-labelled Nitrogen Mustard. Membrane morphology was examined by electron microscopy. Normal membranes were found capable of binding native hemoglobin A and hemoglobin S in similar amounts when incubated at low hemoglobin: membrane ratios, but at high ratios hemoglobin saturation levels of the membranes increased progressively for hemoglobin A, hemoglobin S and hemoglobin A2, respectively, in order of increasing electropositivity. Binding was unaffected by variations in temperature (4-22 degrees C) and altered little by the presence of sulfhydryl reagents, but was inhibited at pH levels above 7.35; disrupted at high ionic strength; and dependent on the ionic composition of the media. These findings suggest that electrostatic, but not hydrophobic or sulfhydryl bonds are important in membrane binding of the hemoglobin under the conditions studied. An increased retention of hemoglobin in preparations of membranes from red cells of patients with sickle cell anemia (homozygote S) was attributable to the dense fraction of homozygote S red cells rich in irreversibly sickled cells, and the latter membranes had a smaller residual binding capacity for new hemoglobin. This suggests that in homozygote S cells which have become irreversibly sickled cells in vivo, there are membrane changes which involve alteration and/or blockade of hemoglobin binding sites. These findings support the notion that hemoglobin participates in the dynamic structure of the red cell membrane in a manner which differs in normal and pathological states.", "contents": "The binding of hemoglobin to membranes of normal and sickle erythrocytes. The binding of hemoglobins A, S, and A2 to red cell membranes prepared by hypotonic lysis from normal blood and blood from persons with sickle cell anemia was quantified under a variety of conditions using hemoglobin labelled by alkylation with 14C-labelled Nitrogen Mustard. Membrane morphology was examined by electron microscopy. Normal membranes were found capable of binding native hemoglobin A and hemoglobin S in similar amounts when incubated at low hemoglobin: membrane ratios, but at high ratios hemoglobin saturation levels of the membranes increased progressively for hemoglobin A, hemoglobin S and hemoglobin A2, respectively, in order of increasing electropositivity. Binding was unaffected by variations in temperature (4-22 degrees C) and altered little by the presence of sulfhydryl reagents, but was inhibited at pH levels above 7.35; disrupted at high ionic strength; and dependent on the ionic composition of the media. These findings suggest that electrostatic, but not hydrophobic or sulfhydryl bonds are important in membrane binding of the hemoglobin under the conditions studied. An increased retention of hemoglobin in preparations of membranes from red cells of patients with sickle cell anemia (homozygote S) was attributable to the dense fraction of homozygote S red cells rich in irreversibly sickled cells, and the latter membranes had a smaller residual binding capacity for new hemoglobin. This suggests that in homozygote S cells which have become irreversibly sickled cells in vivo, there are membrane changes which involve alteration and/or blockade of hemoglobin binding sites. These findings support the notion that hemoglobin participates in the dynamic structure of the red cell membrane in a manner which differs in normal and pathological states."}
{"id": "PMID:235289", "title": "Comparison of the cerebroside sulphatase and the arylsulphatase activity of human sulphatase A in the absence of activators.", "content": "A cerebroside sulphatase (cerebroside-3-sulphate 3 sulphohydrolase, EC 3.1.6.8) assay based on radio thin-layer chromatography is described. The substrate was labelled by the catalytic addition of tritium to cerebroside sulphate. Using this assay the cerebroside sulphatase activity of sulphatase A (Aryl-sulphate sulphohydrolase, EC 3.1.6.1) from human liver and kidney in the absence of activators was investigated. The pH optimum of this reaction depends on the buffer concentration, being pH 4.5 at 50 mM and 5.3 at 10 mM sodium formate. With the latter concentration the apparent Km for cerebroside sulphate is 0.06 mM; SO2-4 and nitrocatechol sulphate inhibit noncompetitively with a Ki of 4.51 mM for Na2SO4 and 0.43 mM for nitrocatechol sulphate. The cerebroside sulphatase activity of sulphatase A is highly dependent on the ionic strength. The optimum sodium formate concentration is 10 mM, and the cerebroside suophatase activity decreases rapidly with increasing buffer concentration. The same concentration dependence is observed in the inhibitory effect of cerebroside sulphate on the arylsulphatase reaction. The inhibition decreases at increasing buffer concentrations, becoming an activation at 70 mM sodium formate. The progress curve of the cerebroside sulphatase reaction shows a deviation from linearity similar to that of the arylsulphatase reaction. Investigation of the effect of preincubation with cerebroside sulphate on the arylsulphatase activity of the enzyme shows that cerebroside sluphatase activity and inactivation of the enzyme by cerebroside sulphate occur simultaneously. These observations are interpreted as supporting the assumption that cerebroside suophate and arylsulphates are degraded at an identical active site on the same enzyme. Differences in the properties of the cerebroside sulphatase and the arylsulphatase reaction of the enzyme may be attributed to the differences in the physiocochemical state of the two substrates.", "contents": "Comparison of the cerebroside sulphatase and the arylsulphatase activity of human sulphatase A in the absence of activators. A cerebroside sulphatase (cerebroside-3-sulphate 3 sulphohydrolase, EC 3.1.6.8) assay based on radio thin-layer chromatography is described. The substrate was labelled by the catalytic addition of tritium to cerebroside sulphate. Using this assay the cerebroside sulphatase activity of sulphatase A (Aryl-sulphate sulphohydrolase, EC 3.1.6.1) from human liver and kidney in the absence of activators was investigated. The pH optimum of this reaction depends on the buffer concentration, being pH 4.5 at 50 mM and 5.3 at 10 mM sodium formate. With the latter concentration the apparent Km for cerebroside sulphate is 0.06 mM; SO2-4 and nitrocatechol sulphate inhibit noncompetitively with a Ki of 4.51 mM for Na2SO4 and 0.43 mM for nitrocatechol sulphate. The cerebroside sulphatase activity of sulphatase A is highly dependent on the ionic strength. The optimum sodium formate concentration is 10 mM, and the cerebroside suophatase activity decreases rapidly with increasing buffer concentration. The same concentration dependence is observed in the inhibitory effect of cerebroside sulphate on the arylsulphatase reaction. The inhibition decreases at increasing buffer concentrations, becoming an activation at 70 mM sodium formate. The progress curve of the cerebroside sulphatase reaction shows a deviation from linearity similar to that of the arylsulphatase reaction. Investigation of the effect of preincubation with cerebroside sulphate on the arylsulphatase activity of the enzyme shows that cerebroside sluphatase activity and inactivation of the enzyme by cerebroside sulphate occur simultaneously. These observations are interpreted as supporting the assumption that cerebroside suophate and arylsulphates are degraded at an identical active site on the same enzyme. Differences in the properties of the cerebroside sulphatase and the arylsulphatase reaction of the enzyme may be attributed to the differences in the physiocochemical state of the two substrates."}
{"id": "PMID:235290", "title": "Effect of alpha2 macroglobulin on some kinetic parameters of trypsin.", "content": "1. Complex formation of trypsin with alpha2 macroglobulin results in marked changes of the Michaelis-Menten constant, pH optimum and sensitivity to ionic strength in a system using N-carbobenzoxy-glycylglycyl-L-arginine-2-naphthylamide as substrate. 2. In contrasts to the inhibition (50%) observed when alpha2 macroglobulin-bound trypsin is assayed under conditions optimal for the free enzyme, there is minimal reduction of activity when determinations are performed at a substrate concentration and pH optimal for the bound enzyme. 3. The changes in substrate concentration and ionic environment required for maximum activity of alpha2 macroglobulin-bound trypsin are similar to those observed with enzymes embedded in polyelectrolyte matrices and may reflect alterations in the microenvironment of the enzyme resulting from conformational changes of the macromolecule during interaction with trypsin. 4. Enzymatic activity of trypsin towards casein is greatly reduced by alpha2 macroglobulin, even under assay conditions optimal for the bound enzyme, confirming previous findings that access to the active center for high-molecular weight substrates is sterically hindered by alpha2 macroglobulin.", "contents": "Effect of alpha2 macroglobulin on some kinetic parameters of trypsin. 1. Complex formation of trypsin with alpha2 macroglobulin results in marked changes of the Michaelis-Menten constant, pH optimum and sensitivity to ionic strength in a system using N-carbobenzoxy-glycylglycyl-L-arginine-2-naphthylamide as substrate. 2. In contrasts to the inhibition (50%) observed when alpha2 macroglobulin-bound trypsin is assayed under conditions optimal for the free enzyme, there is minimal reduction of activity when determinations are performed at a substrate concentration and pH optimal for the bound enzyme. 3. The changes in substrate concentration and ionic environment required for maximum activity of alpha2 macroglobulin-bound trypsin are similar to those observed with enzymes embedded in polyelectrolyte matrices and may reflect alterations in the microenvironment of the enzyme resulting from conformational changes of the macromolecule during interaction with trypsin. 4. Enzymatic activity of trypsin towards casein is greatly reduced by alpha2 macroglobulin, even under assay conditions optimal for the bound enzyme, confirming previous findings that access to the active center for high-molecular weight substrates is sterically hindered by alpha2 macroglobulin."}
{"id": "PMID:235291", "title": "Enzymatic formation of inosine 3',5'-monophosphate and of 2'-deoxyguanosine 3',5'-monophosphate. Inosinate and deoxyguanylate cyclase activity.", "content": "Enzymes in particulate fractions from sea urchin sperm and in soluble fractions from rat lung were shown to catalyze the formation of inosine 3',5'-monophosphate (cyclic IMP) and of 2'-deoxyguanosine 3',5'-monophosphate (cyclic dGMP) from ITP and dGTP, respectively. With sea urchin sperm particulate fractions, Mn2+ was an essential metal cofactor for inosinate, deoxyguanylate, guanylate and adenylate cyclase activities. Heat-inactivation studies differentiated inosinate and deoxyguanylate cyclase activities from adenylate cyclase, but indicated an association of these activities with guanylate cyclase. Preincubation of sea urchin sperm particulate fractions with trypsin altered in a very similar manner guanylate, inosinate, and deoxyguanylate cyclase activities, and various metals and metal-nucleotide combinations protected the three cyclase activities to comparable degrees against trypsin. The relative guanylate, deoxyguanylate and inosinate cyclase activities at 0.1 mM nucleoside triphosphate were 1.0, 0.5 and 0.08, respectively. With these three cyclase activities, plots of reciprocal velocities against reciprocal Mn2+-nucleoside triphosphate concentrations were concave upward, suggesting positive homotropic effects. With rat lung soluble preparations, relative guanylate, deoxyguanylate, inosinate and adenylate cyclase activities at 0.09 mM nucleoside triphosphate were 1.0, 1.7, 0.1 and 0, respectively. MnGTP was a competitive inhibitor of deoxyguanylate cyclase activity (Ki equals 12.2 muM) and MndGTP was a competitive inhibitor of guanylate cyclase activity (Ki equals 16.2 muM). Inhibition studies using ITP were not conducted. When soluble fractions from rat lung were applied to Bio-Gel A 1.5 m columns, elution profiles of guanylate, deoxyguanylate and inosinate cyclase activities were similar. These results suggest that deoxyguanylate, guanylate and inosinate cyclase activities reside within the same protein molecule.", "contents": "Enzymatic formation of inosine 3',5'-monophosphate and of 2'-deoxyguanosine 3',5'-monophosphate. Inosinate and deoxyguanylate cyclase activity. Enzymes in particulate fractions from sea urchin sperm and in soluble fractions from rat lung were shown to catalyze the formation of inosine 3',5'-monophosphate (cyclic IMP) and of 2'-deoxyguanosine 3',5'-monophosphate (cyclic dGMP) from ITP and dGTP, respectively. With sea urchin sperm particulate fractions, Mn2+ was an essential metal cofactor for inosinate, deoxyguanylate, guanylate and adenylate cyclase activities. Heat-inactivation studies differentiated inosinate and deoxyguanylate cyclase activities from adenylate cyclase, but indicated an association of these activities with guanylate cyclase. Preincubation of sea urchin sperm particulate fractions with trypsin altered in a very similar manner guanylate, inosinate, and deoxyguanylate cyclase activities, and various metals and metal-nucleotide combinations protected the three cyclase activities to comparable degrees against trypsin. The relative guanylate, deoxyguanylate and inosinate cyclase activities at 0.1 mM nucleoside triphosphate were 1.0, 0.5 and 0.08, respectively. With these three cyclase activities, plots of reciprocal velocities against reciprocal Mn2+-nucleoside triphosphate concentrations were concave upward, suggesting positive homotropic effects. With rat lung soluble preparations, relative guanylate, deoxyguanylate, inosinate and adenylate cyclase activities at 0.09 mM nucleoside triphosphate were 1.0, 1.7, 0.1 and 0, respectively. MnGTP was a competitive inhibitor of deoxyguanylate cyclase activity (Ki equals 12.2 muM) and MndGTP was a competitive inhibitor of guanylate cyclase activity (Ki equals 16.2 muM). Inhibition studies using ITP were not conducted. When soluble fractions from rat lung were applied to Bio-Gel A 1.5 m columns, elution profiles of guanylate, deoxyguanylate and inosinate cyclase activities were similar. These results suggest that deoxyguanylate, guanylate and inosinate cyclase activities reside within the same protein molecule."}
{"id": "PMID:235292", "title": "Myocardial guanylate cyclase: properties of the enzyme and effects of cholinergic agonists in vitro.", "content": "The characteristics of myocardial guanylate cyclase (GTP pyrophosphatelyase, EC 4.6.1.2) were studied. Specific activity of the myocardial enzyme in five vertebrate species was guinea pig greater than man greater than cat greater than dog greater than rat. In the guinea pig, guanylate cyclase activity was uniformly distributed throughout the anatomical regions of the heart. The major portion of the enzyme activity was retrieved in the supernatant fraction after centrifugation at 12 000 times g. The Km for GTP was similar in supernatant (0.12 mM) and particulate (0.21 mM) preparations, although the Ka for Mn2+ in particulate preparations (0.3-0.6 mM) was less than that observed for guanylate cyclase in the supernatant fraction (0.8-2.0 mM). ATP competitively inhibited supernatant and particulate activity. Addition of 0.005-10.0 mM Ca2+ to assay incubations did not enhance guanylate cyclase activity. Suspension of 105 000 times g supernatant guanylate cyclase preparations with membrane lipids or phosphatidylserine stimulated activity 1.4-4.3 fold, whereas similar treatment of particulate preparations caused little alteration of enzyme activity. Addition of the cholinergic agonists acetylcholine, carbachol or methacholine (10-4-10-8 M) to homogenate, supernatant, particulate and disrupted tissue slice preparations in the presence of 0.0012-1.2 mM GTP, 0.3-10.0 mM Mn2+ and 0.005-10.0 mM Ca2+ or 0.0012-1.2 mM ATP did not stimulate guanylate cyclase activity. Similarly, further stimulation of guanylate cyclase activity was not elicited when enzyme-lipid suspensions were assayed in the presence of cholinergic agents.", "contents": "Myocardial guanylate cyclase: properties of the enzyme and effects of cholinergic agonists in vitro. The characteristics of myocardial guanylate cyclase (GTP pyrophosphatelyase, EC 4.6.1.2) were studied. Specific activity of the myocardial enzyme in five vertebrate species was guinea pig greater than man greater than cat greater than dog greater than rat. In the guinea pig, guanylate cyclase activity was uniformly distributed throughout the anatomical regions of the heart. The major portion of the enzyme activity was retrieved in the supernatant fraction after centrifugation at 12 000 times g. The Km for GTP was similar in supernatant (0.12 mM) and particulate (0.21 mM) preparations, although the Ka for Mn2+ in particulate preparations (0.3-0.6 mM) was less than that observed for guanylate cyclase in the supernatant fraction (0.8-2.0 mM). ATP competitively inhibited supernatant and particulate activity. Addition of 0.005-10.0 mM Ca2+ to assay incubations did not enhance guanylate cyclase activity. Suspension of 105 000 times g supernatant guanylate cyclase preparations with membrane lipids or phosphatidylserine stimulated activity 1.4-4.3 fold, whereas similar treatment of particulate preparations caused little alteration of enzyme activity. Addition of the cholinergic agonists acetylcholine, carbachol or methacholine (10-4-10-8 M) to homogenate, supernatant, particulate and disrupted tissue slice preparations in the presence of 0.0012-1.2 mM GTP, 0.3-10.0 mM Mn2+ and 0.005-10.0 mM Ca2+ or 0.0012-1.2 mM ATP did not stimulate guanylate cyclase activity. Similarly, further stimulation of guanylate cyclase activity was not elicited when enzyme-lipid suspensions were assayed in the presence of cholinergic agents."}
{"id": "PMID:235293", "title": "Purification and characterization of xanthine oxidase from livers of vitamin E deficient rabbits.", "content": "Xanthine oxidase which increases in activity during vitamin E deficiency was purified from livers of deficient rabbits. The procedure incorporates preparative sucrose gradient centrifugation and yields a homogeneous preparation on acrylamide gel electrophoresis. The purified enzyme exhibits a pH optimum of 8.1 and a Km value of 22 muM. Gel filtration chromatography gave the molecular weight of 280 000. Acrylamide gel electrophoresis in the presence of sodium dodecylsulphate reveals two types of subunits of molecular weights 52 000 and 99 000.", "contents": "Purification and characterization of xanthine oxidase from livers of vitamin E deficient rabbits. Xanthine oxidase which increases in activity during vitamin E deficiency was purified from livers of deficient rabbits. The procedure incorporates preparative sucrose gradient centrifugation and yields a homogeneous preparation on acrylamide gel electrophoresis. The purified enzyme exhibits a pH optimum of 8.1 and a Km value of 22 muM. Gel filtration chromatography gave the molecular weight of 280 000. Acrylamide gel electrophoresis in the presence of sodium dodecylsulphate reveals two types of subunits of molecular weights 52 000 and 99 000."}
{"id": "PMID:235294", "title": "Lysine-ketoglutarate reductase in human tissues.", "content": "Lysine-ketoglutarate reductase (saccharopine dehydrogenase (NADP+, lysine-forming) EC 1.5.1.8) from human liver has been partially purified and characterized. A spectrophotometric assay is described. The Michaelis constants have been determined for lysine (1.5-10-3 M), alpha-ketoglutarate (1-10-3 M) and NADPH (8-10-5 M). The pH optimum is 7.8. The enzyme is product inhibited. The specificity of the enzyme, response to inhibitors, pH and thermal stability are reported. Lysine-ketoglutarate reductase is present in high concentration in liver and heart, to a lesser degree in kidney and skin and in trace amounts in several other tissues. Saccharopine dehydrogenase (saccharopine dehydrogenase (NAD+, L-glutamate-forming) EC 1.5.1.9) was demonstrable only in liver and kidney. Lysine-ketoglutarate reductase reacts effectively with delta-hydroxylysine.", "contents": "Lysine-ketoglutarate reductase in human tissues. Lysine-ketoglutarate reductase (saccharopine dehydrogenase (NADP+, lysine-forming) EC 1.5.1.8) from human liver has been partially purified and characterized. A spectrophotometric assay is described. The Michaelis constants have been determined for lysine (1.5-10-3 M), alpha-ketoglutarate (1-10-3 M) and NADPH (8-10-5 M). The pH optimum is 7.8. The enzyme is product inhibited. The specificity of the enzyme, response to inhibitors, pH and thermal stability are reported. Lysine-ketoglutarate reductase is present in high concentration in liver and heart, to a lesser degree in kidney and skin and in trace amounts in several other tissues. Saccharopine dehydrogenase (saccharopine dehydrogenase (NAD+, L-glutamate-forming) EC 1.5.1.9) was demonstrable only in liver and kidney. Lysine-ketoglutarate reductase reacts effectively with delta-hydroxylysine."}
{"id": "PMID:235295", "title": "Effect of enzymic assay conditions on sulfite reduction catalysed by desulfoviridin from Desulfovibrio gigas.", "content": "The type and the amount of end products resulting from sulfite reduction catalysed by a single partially purified desulfoviridin preparation from Desulfovibrio gigas were shown to depend upon the enzymic assay conditions employed. Both manometric and spectrophotometric assays were used, with reduced methyl viologen serving as the electron donor in each system. Trithionate, thiosulfate, tetrathionate and sulfide were identified as possible end products. In the manometric assays, sulfide production was favoured by high reduced methyl viologen concentrations, low sulfite concentrations and a pH value of 7.0 as opposed to 6.0. In the spectrophotometric assays, results approaching the stoichiometric conversion of sulfite to sulfide were obtained only at high initial reduced methyl viologen concentrations.", "contents": "Effect of enzymic assay conditions on sulfite reduction catalysed by desulfoviridin from Desulfovibrio gigas. The type and the amount of end products resulting from sulfite reduction catalysed by a single partially purified desulfoviridin preparation from Desulfovibrio gigas were shown to depend upon the enzymic assay conditions employed. Both manometric and spectrophotometric assays were used, with reduced methyl viologen serving as the electron donor in each system. Trithionate, thiosulfate, tetrathionate and sulfide were identified as possible end products. In the manometric assays, sulfide production was favoured by high reduced methyl viologen concentrations, low sulfite concentrations and a pH value of 7.0 as opposed to 6.0. In the spectrophotometric assays, results approaching the stoichiometric conversion of sulfite to sulfide were obtained only at high initial reduced methyl viologen concentrations."}
{"id": "PMID:235296", "title": "Coupled optical rate determinations of amino acid oxidase activity.", "content": "Methods are described in which liberation of ammonia from amino acid substrates by the D- and L-amino acid oxidases may be coupled with the NADH-dependent reductive amination of 2-oxoglutarate catalysed by exogenous glutamate dehydrogenase (L-glutamate: NAD oxidoreductase (deaminating), EC 1.4.1.2). The inhibition of D-amino acid oxidase (D-amino acid:O2 oxidoreductase (deaminating), EC 1.4.3.3) by ADP needed to activate and stabilise glutamate dehydrogenase was relieved by FAD, and the substrate was D-alanine at approximately 6-fold Km concentration. Neither FAD or FMN were required in the L-amino acid oxidase (L-amino acid:O2 oxidoreductase (deaminating), EC 1.4.3.2) assay; this utilised L-leucine as substrate in a concentration approximately 7-fold the Km value. The methods were reasonably sensitive and precise, and a linear relationship between activity and enzyme concentration prevailed up to an absorbance change of 0.050 per min. They have the advantage of being amenable to automation and to employment of fluorescence techniques should greater sensitivity be required.", "contents": "Coupled optical rate determinations of amino acid oxidase activity. Methods are described in which liberation of ammonia from amino acid substrates by the D- and L-amino acid oxidases may be coupled with the NADH-dependent reductive amination of 2-oxoglutarate catalysed by exogenous glutamate dehydrogenase (L-glutamate: NAD oxidoreductase (deaminating), EC 1.4.1.2). The inhibition of D-amino acid oxidase (D-amino acid:O2 oxidoreductase (deaminating), EC 1.4.3.3) by ADP needed to activate and stabilise glutamate dehydrogenase was relieved by FAD, and the substrate was D-alanine at approximately 6-fold Km concentration. Neither FAD or FMN were required in the L-amino acid oxidase (L-amino acid:O2 oxidoreductase (deaminating), EC 1.4.3.2) assay; this utilised L-leucine as substrate in a concentration approximately 7-fold the Km value. The methods were reasonably sensitive and precise, and a linear relationship between activity and enzyme concentration prevailed up to an absorbance change of 0.050 per min. They have the advantage of being amenable to automation and to employment of fluorescence techniques should greater sensitivity be required."}
{"id": "PMID:235297", "title": "Kinetic properties of an enzyme highly enriched in carbon-13.", "content": "Preparations of Candida utilis 6-phosphogluconate dehydrogenase with extreme variation in carbon isotope composition have been obtained. Molecular activities, pH optima and substrate affinities of these enzyme preparations have been measured. It was observed that any effect of isotope composition on these physiologically important properties is minimal.", "contents": "Kinetic properties of an enzyme highly enriched in carbon-13. Preparations of Candida utilis 6-phosphogluconate dehydrogenase with extreme variation in carbon isotope composition have been obtained. Molecular activities, pH optima and substrate affinities of these enzyme preparations have been measured. It was observed that any effect of isotope composition on these physiologically important properties is minimal."}
{"id": "PMID:235298", "title": "Glutamate dehydrogenase from Escherichia coli: induction, purification and properties of the enzyme.", "content": "When Escherichia coli was grown in a minimum medium with glucose as sole carbon source and a proper level of ammonia, NADP+ specific glutamate dehydrogenase (L-glutamate: NADP+ oxidoreductase (deaminating), ED 1.4.1.4) was induced. The enzyme was solubilized by French press treatment and purified to homogeneity by (NH4)2SO4 fractionation, heat treatment followed by DEAE-cellulose, hydroxylapatite and Bio-Gel chromatography with an overall yield of 30%. The enzyme proved to be heat stable and relatively resistant to protein denaturants. The optimum of enzymic activity for the reductive amination is at pH 8 and at pH 9 for the oxidative deamination. The activity is affected by adenine nucleotides. The molecular weight (about 250 000 for the native form and 46 000 for the inactive subunit) and amino acid composition, suggest strict similarities with the NADP+ enzyme from fungal origin.", "contents": "Glutamate dehydrogenase from Escherichia coli: induction, purification and properties of the enzyme. When Escherichia coli was grown in a minimum medium with glucose as sole carbon source and a proper level of ammonia, NADP+ specific glutamate dehydrogenase (L-glutamate: NADP+ oxidoreductase (deaminating), ED 1.4.1.4) was induced. The enzyme was solubilized by French press treatment and purified to homogeneity by (NH4)2SO4 fractionation, heat treatment followed by DEAE-cellulose, hydroxylapatite and Bio-Gel chromatography with an overall yield of 30%. The enzyme proved to be heat stable and relatively resistant to protein denaturants. The optimum of enzymic activity for the reductive amination is at pH 8 and at pH 9 for the oxidative deamination. The activity is affected by adenine nucleotides. The molecular weight (about 250 000 for the native form and 46 000 for the inactive subunit) and amino acid composition, suggest strict similarities with the NADP+ enzyme from fungal origin."}
{"id": "PMID:235299", "title": "A purification procedure for the isolation of homogeneous preparations of bovine aorta amine oxidase and a study of its lysyl oxidase activity.", "content": "It has been reported that bovine aorta amine oxidase oxidizes lysine residues in tropoelastin to allysine (Rucker, R.B. and O'Dell, B.L. (1971) Biochim. Biophys. Acta 235, 32-43). Pure bovine aorta amine oxidase was isolate by DEAE-cellulose, hydroxylapatite, Bio-Gel A-1.5 m and concanavalin A-Sepharose 4B chromatography. Enzymatic, chromatographic and immunochemical tests disclosed that pure bovine aorta amine oxidase was not a lysyl oxidase capable of oxidizing the lysine residues of tropoelastin to allysine; The bovine aorta amine oxidase preparation used by Rucker and O'Dell appears to have been contaminated with lysyl oxidase which is the emzyme that oxidizes some of the lysine residues in tropoelastin and tropocollagen to allysine.", "contents": "A purification procedure for the isolation of homogeneous preparations of bovine aorta amine oxidase and a study of its lysyl oxidase activity. It has been reported that bovine aorta amine oxidase oxidizes lysine residues in tropoelastin to allysine (Rucker, R.B. and O'Dell, B.L. (1971) Biochim. Biophys. Acta 235, 32-43). Pure bovine aorta amine oxidase was isolate by DEAE-cellulose, hydroxylapatite, Bio-Gel A-1.5 m and concanavalin A-Sepharose 4B chromatography. Enzymatic, chromatographic and immunochemical tests disclosed that pure bovine aorta amine oxidase was not a lysyl oxidase capable of oxidizing the lysine residues of tropoelastin to allysine; The bovine aorta amine oxidase preparation used by Rucker and O'Dell appears to have been contaminated with lysyl oxidase which is the emzyme that oxidizes some of the lysine residues in tropoelastin and tropocollagen to allysine."}
{"id": "PMID:235300", "title": "Effects of a nitrate reductase inactivating enzyme and NAD(P)H on the nitrate reductase from higher plants and Neurospora.", "content": "Evidence is presented which suggests that the NAD(P)H-cytochrome c reductase component of nitrate reductase is the main site of action of the inactivating enzyme. When tested on the nitrate reductase (NADH) from the maize root and scutella, the NADH-cytochrome c reductase was inactivated at a greater rate than was the FADH2-nitrate reductase component. With the Neurospora nitrate reductase (NADPH) only the NADPH-cytochrome c reductase was inactivated. p-Chloromercuribenzoate at 50 muM, which gave almost complete inhibition of the NADH-cytochrome c reductase fraction of the maize nitrate reductase, had no marked effect on the action of the inactivating enzyme. A reversible inactivation of the maize nitrate reductase has been shown to occur during incubation with NAD(P)H. In contrast to the action of the inactivating enzyme, it is the FADH2-nitrate reductase alone which is inactivated. No inactivation of the Neurospora nitrate reductase was produced by NAD(P)H alone and also in the presence of FAD. The lack of effect of the inactivating enzyme and NAD(P)H on the FADH2-nitrate reductase of Neurospora suggests some differences in its structure or conformation from that of the maize enzyme. A low level of cyanide (0.4 mu M) markedly enhanced the action of NAD(P)H on the maize enzyme; Cyanide at a higher level (6 mu M) did give inactivation of the Neurospora nitrate reductase in the presence of NADPH and FAD. The maize nitrate reductase, when partially inactivated by NADH and cyanide, was not altered as a substrate for the inactivating enzyme. The maize root inactivating enzyme was also shown to inactivate the nitrate reductase (NADH) in the pea leaf. It had no effect on the nitrate reductase from either Pseudomonas denitrificans or Nitrobacter agilis.", "contents": "Effects of a nitrate reductase inactivating enzyme and NAD(P)H on the nitrate reductase from higher plants and Neurospora. Evidence is presented which suggests that the NAD(P)H-cytochrome c reductase component of nitrate reductase is the main site of action of the inactivating enzyme. When tested on the nitrate reductase (NADH) from the maize root and scutella, the NADH-cytochrome c reductase was inactivated at a greater rate than was the FADH2-nitrate reductase component. With the Neurospora nitrate reductase (NADPH) only the NADPH-cytochrome c reductase was inactivated. p-Chloromercuribenzoate at 50 muM, which gave almost complete inhibition of the NADH-cytochrome c reductase fraction of the maize nitrate reductase, had no marked effect on the action of the inactivating enzyme. A reversible inactivation of the maize nitrate reductase has been shown to occur during incubation with NAD(P)H. In contrast to the action of the inactivating enzyme, it is the FADH2-nitrate reductase alone which is inactivated. No inactivation of the Neurospora nitrate reductase was produced by NAD(P)H alone and also in the presence of FAD. The lack of effect of the inactivating enzyme and NAD(P)H on the FADH2-nitrate reductase of Neurospora suggests some differences in its structure or conformation from that of the maize enzyme. A low level of cyanide (0.4 mu M) markedly enhanced the action of NAD(P)H on the maize enzyme; Cyanide at a higher level (6 mu M) did give inactivation of the Neurospora nitrate reductase in the presence of NADPH and FAD. The maize nitrate reductase, when partially inactivated by NADH and cyanide, was not altered as a substrate for the inactivating enzyme. The maize root inactivating enzyme was also shown to inactivate the nitrate reductase (NADH) in the pea leaf. It had no effect on the nitrate reductase from either Pseudomonas denitrificans or Nitrobacter agilis."}
{"id": "PMID:235301", "title": "Studies on the in vitro inactivation of the Neurospora crassa assimilatory nitrite reductase in the presence of reduced pyridine nucleotides plus flavin.", "content": "In vitro inactivation of Neurospora crassa nitrite reductase (NAD(P)H: nitrite oxidoreductase, EC 1.6.6.4) can be obtained by preincubation of the enzyme with reduced pyridine nucleotide plus FAD. The presence of nitrite or hydroxylamine, electron acceptors for the N. crassa nitrite reductase, or cyanide, sulfite or arsenite, competitive inhibitors with respect to nitrite of this enzyme, protects the enzyme against this inactivation. Anaerobic experiments reveal that oxygen is required in order to obtain complete inactivation of nitrite reductase by preincubation with reduced pyridine nucleotide plus FAD. Also, inactivation is prevented if catalase is included in the preincubation mixture. The presence of hydrogen peroxide in the preincubation mixture increases the sensitivity of nitrite reductase to the in vitro FAD-dependent NAD(P)H inactivation. Neither electron acceptors, competitive inhibitors nor catalase, agents which protect the enzyme against the FAD-dependent NAD(P)H inactivation, can reverse this process once it has occurred.", "contents": "Studies on the in vitro inactivation of the Neurospora crassa assimilatory nitrite reductase in the presence of reduced pyridine nucleotides plus flavin. In vitro inactivation of Neurospora crassa nitrite reductase (NAD(P)H: nitrite oxidoreductase, EC 1.6.6.4) can be obtained by preincubation of the enzyme with reduced pyridine nucleotide plus FAD. The presence of nitrite or hydroxylamine, electron acceptors for the N. crassa nitrite reductase, or cyanide, sulfite or arsenite, competitive inhibitors with respect to nitrite of this enzyme, protects the enzyme against this inactivation. Anaerobic experiments reveal that oxygen is required in order to obtain complete inactivation of nitrite reductase by preincubation with reduced pyridine nucleotide plus FAD. Also, inactivation is prevented if catalase is included in the preincubation mixture. The presence of hydrogen peroxide in the preincubation mixture increases the sensitivity of nitrite reductase to the in vitro FAD-dependent NAD(P)H inactivation. Neither electron acceptors, competitive inhibitors nor catalase, agents which protect the enzyme against the FAD-dependent NAD(P)H inactivation, can reverse this process once it has occurred."}
{"id": "PMID:235302", "title": "A cyclic adenosine 3',5'-monophosphate-dependent histone kinase from pig brain. Purification and some properties of the enzyme.", "content": "A cyclic adenosine 3',5'-monophosphate-dependent histone kinase (ATP: protein phosphotransferase, EC 2.7.1.37) was isolated from pig brain. The enzyme has been purified 1140-fold; it is homogeneous on polyacrylamide gel electrophoresis and gel filtration. The estimated molecular weight of the enzyme is 120 000. Histone kinase dissociates into a catalytic subunit and a regulatory one (molecular weights 40 000 and 90 000, respectively). The catalytic subunit has been obtained in homogeneous state as evidenced by sodium dodecylsulphate-polyacrylamide gel electrophoresis. At all purification steps, enzymatic activity is stimulated 5-fold by cyclic AMP. An apparent Km value for cyclic AMP is about 3.3 - 10- minus 7 M. In the presence of cyclic AMP(5 - 10- minus 6 M), the Km value for ATP and F1 histone were 1.2 - 10- minus five and 3 - 10- minus 5 M, respectively. Optimum pH value for histone kinase is 6.5, its isoelectric point is situated at pH 4.6. The purified enzyme displays high specificity for the lysine-rich and moderately lysine-rich histones F1, F2a2 and F2b. Arginine-rich histones and other known protein substrates for cyclic AMP-dependent protein kinases (casein, Escherichia coli RNA polymerase, etc.) are extremely poor substrates for this enzyme.", "contents": "A cyclic adenosine 3',5'-monophosphate-dependent histone kinase from pig brain. Purification and some properties of the enzyme. A cyclic adenosine 3',5'-monophosphate-dependent histone kinase (ATP: protein phosphotransferase, EC 2.7.1.37) was isolated from pig brain. The enzyme has been purified 1140-fold; it is homogeneous on polyacrylamide gel electrophoresis and gel filtration. The estimated molecular weight of the enzyme is 120 000. Histone kinase dissociates into a catalytic subunit and a regulatory one (molecular weights 40 000 and 90 000, respectively). The catalytic subunit has been obtained in homogeneous state as evidenced by sodium dodecylsulphate-polyacrylamide gel electrophoresis. At all purification steps, enzymatic activity is stimulated 5-fold by cyclic AMP. An apparent Km value for cyclic AMP is about 3.3 - 10- minus 7 M. In the presence of cyclic AMP(5 - 10- minus 6 M), the Km value for ATP and F1 histone were 1.2 - 10- minus five and 3 - 10- minus 5 M, respectively. Optimum pH value for histone kinase is 6.5, its isoelectric point is situated at pH 4.6. The purified enzyme displays high specificity for the lysine-rich and moderately lysine-rich histones F1, F2a2 and F2b. Arginine-rich histones and other known protein substrates for cyclic AMP-dependent protein kinases (casein, Escherichia coli RNA polymerase, etc.) are extremely poor substrates for this enzyme."}
{"id": "PMID:235303", "title": "Biosynthesis of acid phosphatase of baker's yeast. Characterization of a protoplast-bound fraction containing precursors of the exo-enzyme.", "content": "1. Yeast protoplasts, secreting acid phosphatase (orthophosphoric-monoester phosphohydrolase (acid optimum) EC 3.1.3.2) contain a small amount of firmly bound enzyme, even after lysis (Van Rijn, H.J.M., Boer, P. and Steyn-Parv\u00e9, E.P. (1972) Biochim. Biophys. Acta 268, 431-441). The major part (70%) of this protoplast-bound acid phosphatase can be solubilized by nonionic detergents, such as Triton X-100. 2. The kinetics of radioactive amino acid incorporation in the solubilized and in the secreted enzyme has been estimated by pulse-chase labelling of secreting protoplasts, followed by fractionation and counting radioactivity in the enzyme band in polyacrylamide gels after electrophoresis at pH 5.0. A precursor-product relationship between the Triton X-100-extractable fraction of the protoplast-bound acid phosphatase and the secreted enzyme is apparent. 3. The solubilized acid phosphatase is essentially indistinguishable from the secreted enzyme with regard to a number of enzymatic properties and its stability towards pH and temperature. Both enzymes also behave alike on polyacrylamide-gel electrophoresis, producing a single acid phosphatase band with glycoprotein character and comparable mobility. 4. A striking difference is seen in isopycnic equilibrium sedimentation in CsCl: the secreted acid phosphatase is homogeneous, with a buoyant density of p equals 1.47 g/cm3, while the Triton X-100-extractable part of the protoplast-bound acid phosphatase is heterogeneous; besides heavier material a major component with buoyant density of p equals 1.37 g/cm3 is always visible.", "contents": "Biosynthesis of acid phosphatase of baker's yeast. Characterization of a protoplast-bound fraction containing precursors of the exo-enzyme. 1. Yeast protoplasts, secreting acid phosphatase (orthophosphoric-monoester phosphohydrolase (acid optimum) EC 3.1.3.2) contain a small amount of firmly bound enzyme, even after lysis (Van Rijn, H.J.M., Boer, P. and Steyn-Parv\u00e9, E.P. (1972) Biochim. Biophys. Acta 268, 431-441). The major part (70%) of this protoplast-bound acid phosphatase can be solubilized by nonionic detergents, such as Triton X-100. 2. The kinetics of radioactive amino acid incorporation in the solubilized and in the secreted enzyme has been estimated by pulse-chase labelling of secreting protoplasts, followed by fractionation and counting radioactivity in the enzyme band in polyacrylamide gels after electrophoresis at pH 5.0. A precursor-product relationship between the Triton X-100-extractable fraction of the protoplast-bound acid phosphatase and the secreted enzyme is apparent. 3. The solubilized acid phosphatase is essentially indistinguishable from the secreted enzyme with regard to a number of enzymatic properties and its stability towards pH and temperature. Both enzymes also behave alike on polyacrylamide-gel electrophoresis, producing a single acid phosphatase band with glycoprotein character and comparable mobility. 4. A striking difference is seen in isopycnic equilibrium sedimentation in CsCl: the secreted acid phosphatase is homogeneous, with a buoyant density of p equals 1.47 g/cm3, while the Triton X-100-extractable part of the protoplast-bound acid phosphatase is heterogeneous; besides heavier material a major component with buoyant density of p equals 1.37 g/cm3 is always visible."}
{"id": "PMID:235304", "title": "Phosphoprotein phosphatase in the central nervous system of Manduca sexta.", "content": "The existence and some enzymological properties of phosphoprotein phosphatase (EC 3.1.3.16) have been established in the larval central nervous system of the tobacco hornworm, Manduca sexta (Lepidoptera: Sphingidae). A simple, sensitive and reproducible assay employing 32-P-labeled protamine as a phosphoprotein substrate was employed to measure phosphatase activity in both soluble and particulate fractions of the insect nerve cord. The specific activity of soluble phosphatase in the Manduca sexta central nervous system is of the same order of magnitude as that in mammalian brain. Nerve cord phosphoprotamine phosphatase activity may be stimulated by a variety of monovalent salts, the optimal concentration of NaCl or KCl being 0.2 molar. Activity does not appear to be dependent on bivalent metals and is stimulated by EDTA. A reduced sulfhydryl group is obligatory for maximum activity. Phosphatase could be greatly inhibited by sodium fluoride, ATP and GTP. Cyclic AMP and cyclic GMP are without effect on enzyme activity. Although most of the phosphatase activity in the insect nerve cord appears to be of cytosolic origin, much latent activity can be unmasked by incubating membranous fractions with Triton X-100. In contrast to soluble phosphatase, the detergent-solubilized activity is moderately stimulated by Mn-2+.?", "contents": "Phosphoprotein phosphatase in the central nervous system of Manduca sexta. The existence and some enzymological properties of phosphoprotein phosphatase (EC 3.1.3.16) have been established in the larval central nervous system of the tobacco hornworm, Manduca sexta (Lepidoptera: Sphingidae). A simple, sensitive and reproducible assay employing 32-P-labeled protamine as a phosphoprotein substrate was employed to measure phosphatase activity in both soluble and particulate fractions of the insect nerve cord. The specific activity of soluble phosphatase in the Manduca sexta central nervous system is of the same order of magnitude as that in mammalian brain. Nerve cord phosphoprotamine phosphatase activity may be stimulated by a variety of monovalent salts, the optimal concentration of NaCl or KCl being 0.2 molar. Activity does not appear to be dependent on bivalent metals and is stimulated by EDTA. A reduced sulfhydryl group is obligatory for maximum activity. Phosphatase could be greatly inhibited by sodium fluoride, ATP and GTP. Cyclic AMP and cyclic GMP are without effect on enzyme activity. Although most of the phosphatase activity in the insect nerve cord appears to be of cytosolic origin, much latent activity can be unmasked by incubating membranous fractions with Triton X-100. In contrast to soluble phosphatase, the detergent-solubilized activity is moderately stimulated by Mn-2+.?"}
{"id": "PMID:235305", "title": "Purification and properties of a beta-1,6-clucosidase from Flavobacterium.", "content": "An intracellular beta-1,6-glucosidase (beta-D-glucoside glucohydrolase, EC 3.2.1.21) was produced semiconstitutively by Flavobacterium M64. This enzyme was purified 180-fold by fractionation with ammonium sulfate followed by chromatographies on carboxymethylcellulose, hydroxyapatite and Sephadex G-100. The final preparation appeared homogeneous on disc electrophoresis on polyacrylamide gel. The molecular weight of the enzyme was determined to be ca. 59 000 by Sephadex G-100 gel filtration and sodium dodecylsulfate-polyacrylamide gel electrophoresis. The optimum pH of the enzyme was 5.8 and the optimum temperature was 40 degrees C. The enzyme readily hydrolyzed oligomers with beta-a,6-glucosidic linkages, converting them to glucose. The Km values for gentio-biose, -triose, -tetraose and -pentaose were 2.8, 3.0, 4.2 and 4.6 times 10- minus 4 M, respectively. The rates of their hydrolyses decreased with increase in their chain lengths. The enzyme was concluded to be a beta-1,6-glucosidase from its substrate specificity, production of glucose, transferring ability and inhibition by glucono-delta-lactone. The enzyme activity was inhibited by Hg-2+, Cu-2+, Ag-+, Fe-3+, p-chloromercuribenzoate, N-ethylmaleimide, glucose and trishydroxyaminomethane (Tris) but not by ethylenediaminetetraacetic acid.", "contents": "Purification and properties of a beta-1,6-clucosidase from Flavobacterium. An intracellular beta-1,6-glucosidase (beta-D-glucoside glucohydrolase, EC 3.2.1.21) was produced semiconstitutively by Flavobacterium M64. This enzyme was purified 180-fold by fractionation with ammonium sulfate followed by chromatographies on carboxymethylcellulose, hydroxyapatite and Sephadex G-100. The final preparation appeared homogeneous on disc electrophoresis on polyacrylamide gel. The molecular weight of the enzyme was determined to be ca. 59 000 by Sephadex G-100 gel filtration and sodium dodecylsulfate-polyacrylamide gel electrophoresis. The optimum pH of the enzyme was 5.8 and the optimum temperature was 40 degrees C. The enzyme readily hydrolyzed oligomers with beta-a,6-glucosidic linkages, converting them to glucose. The Km values for gentio-biose, -triose, -tetraose and -pentaose were 2.8, 3.0, 4.2 and 4.6 times 10- minus 4 M, respectively. The rates of their hydrolyses decreased with increase in their chain lengths. The enzyme was concluded to be a beta-1,6-glucosidase from its substrate specificity, production of glucose, transferring ability and inhibition by glucono-delta-lactone. The enzyme activity was inhibited by Hg-2+, Cu-2+, Ag-+, Fe-3+, p-chloromercuribenzoate, N-ethylmaleimide, glucose and trishydroxyaminomethane (Tris) but not by ethylenediaminetetraacetic acid."}
{"id": "PMID:235306", "title": "Proteolytic degradation of insulin and glucagon.", "content": "The degradation of insulin and glucagon by a highly purified enzyme isolated from rat skeletal muscle was investigated. A sensitive assay for proteolytic degradation of insulin and glucagon using fluorescamine to detect an increase in primary amine groups was established. As measured by an increase in fluorescamine reactive materials, insulin was rapidly degraded by this highly purified enzyme without requiring initial disulfide cleavage. Associated with the increase in fluorescamine reactive materials was a decrease in immunoassayable insulinmglucagon wal also proteolytically degraded by this enzyme but a number of other peptides and proteins including proinsulin, and A and B chains of insulin were not degraded. Thus, we have demonstrated that insulin (and glucagon) can be proteolytically degraded by an enzyme isolated from an insulin sensitive tissue, skeletal muscle. Proteolytic degradation by this enzyme requires the intact insulin molecule rather than separate A and B chains.", "contents": "Proteolytic degradation of insulin and glucagon. The degradation of insulin and glucagon by a highly purified enzyme isolated from rat skeletal muscle was investigated. A sensitive assay for proteolytic degradation of insulin and glucagon using fluorescamine to detect an increase in primary amine groups was established. As measured by an increase in fluorescamine reactive materials, insulin was rapidly degraded by this highly purified enzyme without requiring initial disulfide cleavage. Associated with the increase in fluorescamine reactive materials was a decrease in immunoassayable insulinmglucagon wal also proteolytically degraded by this enzyme but a number of other peptides and proteins including proinsulin, and A and B chains of insulin were not degraded. Thus, we have demonstrated that insulin (and glucagon) can be proteolytically degraded by an enzyme isolated from an insulin sensitive tissue, skeletal muscle. Proteolytic degradation by this enzyme requires the intact insulin molecule rather than separate A and B chains."}
{"id": "PMID:235307", "title": "Purification and properties of a constitutive beta-lactamase from Pseudomonas aeruginosa strain Dalgleish.", "content": "1. The beta-lactamase (penicillin amido-beta-lactamhydrolase EC 3.5.2.6) appeared to be periplasmic rather than truly intracellular, since it was released by freeze-thawing without gross morphological changes in the cell. 2. The partially purified enzyme had pI between 5.0 and 5.5, mol. wt 32 000 and a broad pH vs activity profile with a maximum at pH 8. 3. The cephalosporins tested were hydrolysed less rapidly than most of the penicillins, and the Km values for penicillins were lower than for cephalosporins. However cloxacillin was hydrolysed very slowly although it was strongly bound. The substrate-induced inactivation common to many beta-lactamases was particularly marked with cephaloridine and cloxacillinmthe cloxacillin-induced inactivation was shown to be reversible.", "contents": "Purification and properties of a constitutive beta-lactamase from Pseudomonas aeruginosa strain Dalgleish. 1. The beta-lactamase (penicillin amido-beta-lactamhydrolase EC 3.5.2.6) appeared to be periplasmic rather than truly intracellular, since it was released by freeze-thawing without gross morphological changes in the cell. 2. The partially purified enzyme had pI between 5.0 and 5.5, mol. wt 32 000 and a broad pH vs activity profile with a maximum at pH 8. 3. The cephalosporins tested were hydrolysed less rapidly than most of the penicillins, and the Km values for penicillins were lower than for cephalosporins. However cloxacillin was hydrolysed very slowly although it was strongly bound. The substrate-induced inactivation common to many beta-lactamases was particularly marked with cephaloridine and cloxacillinmthe cloxacillin-induced inactivation was shown to be reversible."}
{"id": "PMID:235308", "title": "Catalytic and thermodynamic properties of the urocanate hydratase reaction.", "content": "Urocanate hydratase (4-imidazolone-5-propionate hydro-lyase, EC 4.2.1.49) isolated from Pseudomonas putida contains covalently bound alpha-ketobutyrate as its cofactor. In the process of examining the mechanism by which alpha-ketobutyrate serves in this capacity, various thermodynamic parameters and temperature effects on urocanate hydratase activity were determined. As the equilibrium constant at 15 degrees C for imidazooone propionate formation from urocanate is approximately 69, regardless of whether urocanic acid or chemically synthesized imidazolone propionate is used as the initial substrate, it is concluded that the reaction is freely reversible. DeltaG degrees ', deltaH degrees ' and deltaS degrees ' were --2.5 kcal/mole, +5.2 kcal/mole and +26 cal/deg mole, respectively. Measurement of first-order reaction rates at various temperatures, in order to calculate the Arrhenius activation energy, showed a sharp break in the Arrhenius plot at 29 degrees C. Further examination of this phenomenon by determining s20,w values of urocanate hydratase as a function of temperature revealed a dramatic change at 31 degrees C. Since the enzyme in both experiments reverts to its original state when the temperature is lowered back below the transition point, it is proposed that urocanate hydratase undergoes a reversible conformational change or partial dissociation which affects its catalytic properties in the range of 29--31 degrees C.", "contents": "Catalytic and thermodynamic properties of the urocanate hydratase reaction. Urocanate hydratase (4-imidazolone-5-propionate hydro-lyase, EC 4.2.1.49) isolated from Pseudomonas putida contains covalently bound alpha-ketobutyrate as its cofactor. In the process of examining the mechanism by which alpha-ketobutyrate serves in this capacity, various thermodynamic parameters and temperature effects on urocanate hydratase activity were determined. As the equilibrium constant at 15 degrees C for imidazooone propionate formation from urocanate is approximately 69, regardless of whether urocanic acid or chemically synthesized imidazolone propionate is used as the initial substrate, it is concluded that the reaction is freely reversible. DeltaG degrees ', deltaH degrees ' and deltaS degrees ' were --2.5 kcal/mole, +5.2 kcal/mole and +26 cal/deg mole, respectively. Measurement of first-order reaction rates at various temperatures, in order to calculate the Arrhenius activation energy, showed a sharp break in the Arrhenius plot at 29 degrees C. Further examination of this phenomenon by determining s20,w values of urocanate hydratase as a function of temperature revealed a dramatic change at 31 degrees C. Since the enzyme in both experiments reverts to its original state when the temperature is lowered back below the transition point, it is proposed that urocanate hydratase undergoes a reversible conformational change or partial dissociation which affects its catalytic properties in the range of 29--31 degrees C."}
{"id": "PMID:235309", "title": "Renal cortex guanylate cyclase. Preferential enrichment in glomerular membranes.", "content": "1. The localisation and some of the properties of rabbit kidney cortex guanylate cyclase (GTP pyrophosphatase lyase (cyclizing) EC 4.6.1.2) have been studied. Upon fractionation of dissociated renal cortex, guanylate cyclase activity was preferentially enriched in fractions of pure glomeruli, where its specific activity was 44.5 times that measured in tubular fragments. Most, if not all, of the glomerular activity was found to be firmly membrane-bound, whereas the guanylate cyclase activity of the tubules was mainly soluble. Therefore, particulate guanylate cyclase activity could serve as marker enzyme for kidney glomeruli. 2. All hormones or hormone-like agents tested were without effect on kidney guanylate cyclase activity. Triton X-100 stimulated both glomerular and tubular activity. 3. Considering the high cyclic GMP forming capacity of kidney glomeruli, part of the cyclic GMP found in urine might be synthetized locally in these structures.", "contents": "Renal cortex guanylate cyclase. Preferential enrichment in glomerular membranes. 1. The localisation and some of the properties of rabbit kidney cortex guanylate cyclase (GTP pyrophosphatase lyase (cyclizing) EC 4.6.1.2) have been studied. Upon fractionation of dissociated renal cortex, guanylate cyclase activity was preferentially enriched in fractions of pure glomeruli, where its specific activity was 44.5 times that measured in tubular fragments. Most, if not all, of the glomerular activity was found to be firmly membrane-bound, whereas the guanylate cyclase activity of the tubules was mainly soluble. Therefore, particulate guanylate cyclase activity could serve as marker enzyme for kidney glomeruli. 2. All hormones or hormone-like agents tested were without effect on kidney guanylate cyclase activity. Triton X-100 stimulated both glomerular and tubular activity. 3. Considering the high cyclic GMP forming capacity of kidney glomeruli, part of the cyclic GMP found in urine might be synthetized locally in these structures."}
{"id": "PMID:235310", "title": "An acridine probe into the physiological state of the cell.", "content": "Acridine orange was used as a probe to look into the physiological state of the yeast cell, particularly as regards the change in the properties of the membrane (which acts as a barrier against the incoming acridine orange) and the availability of binding sites for acridine orange in chromosomal DNA during growth. After acridine orange had been introduced into the cell, the genetic change at a specific locus with incubation time was measured photodynamically. A three-fold increase in the rate of penetration of acridine orange into the cell was observed, for instance, in going from the resting phase to the dividing phase. A five-fold increase was observed in the number of binding sites in chromosomal DNA under the same transition of the cell. These two parameters may be useful as a measure of the physiological changes in the cell. Some environmental factors such as pH and temperature were also demonstrated to affect the parameters.", "contents": "An acridine probe into the physiological state of the cell. Acridine orange was used as a probe to look into the physiological state of the yeast cell, particularly as regards the change in the properties of the membrane (which acts as a barrier against the incoming acridine orange) and the availability of binding sites for acridine orange in chromosomal DNA during growth. After acridine orange had been introduced into the cell, the genetic change at a specific locus with incubation time was measured photodynamically. A three-fold increase in the rate of penetration of acridine orange into the cell was observed, for instance, in going from the resting phase to the dividing phase. A five-fold increase was observed in the number of binding sites in chromosomal DNA under the same transition of the cell. These two parameters may be useful as a measure of the physiological changes in the cell. Some environmental factors such as pH and temperature were also demonstrated to affect the parameters."}
{"id": "PMID:235312", "title": "On the molecular weight of thiosulfate sulfurtransferase.", "content": "Bovine liver thiosulfate sulfurtransferase (rhodanese) (EC 2.8.1.1) HAS BEEN REPORTED TO EXIST IN SOLUTION IN A RAPID, PH-dependent equilibrium between monomeric and dimeric forms of molecular weights 18 500 and 37 000 (Volini, M., DeToma, F. and Westley, J. (1967), J. Biol. Chem. 242, 5220). We have reinvestigated the proposed dissociation using sodium dodecylsulfate-polyacrylamide gel electrophoresis. The smallest rhodanese species observed has a molecular weight around 35 000, which is not reduced by severe denaturing conditions, including alkylation in 8 M guanidine-HCl or dialysis against 2% sodium dodecylsulfate and 5% mercaptoethanol. After limited CNBr cleavage, intermediate products of greater than 18 500 molecular weight are formed. The apparent molecular weight of these intermediate fragments is not changed by addition of mercaptoethanol. The total apparent molecular weights of the CNBr fragments after exhaustive cleavage is approx. 45 000 plus or minus 15 000. These results are not consistent with a monomer molecular weight of approx. 18 500 for thiosulfate sulfurtransferase.", "contents": "On the molecular weight of thiosulfate sulfurtransferase. Bovine liver thiosulfate sulfurtransferase (rhodanese) (EC 2.8.1.1) HAS BEEN REPORTED TO EXIST IN SOLUTION IN A RAPID, PH-dependent equilibrium between monomeric and dimeric forms of molecular weights 18 500 and 37 000 (Volini, M., DeToma, F. and Westley, J. (1967), J. Biol. Chem. 242, 5220). We have reinvestigated the proposed dissociation using sodium dodecylsulfate-polyacrylamide gel electrophoresis. The smallest rhodanese species observed has a molecular weight around 35 000, which is not reduced by severe denaturing conditions, including alkylation in 8 M guanidine-HCl or dialysis against 2% sodium dodecylsulfate and 5% mercaptoethanol. After limited CNBr cleavage, intermediate products of greater than 18 500 molecular weight are formed. The apparent molecular weight of these intermediate fragments is not changed by addition of mercaptoethanol. The total apparent molecular weights of the CNBr fragments after exhaustive cleavage is approx. 45 000 plus or minus 15 000. These results are not consistent with a monomer molecular weight of approx. 18 500 for thiosulfate sulfurtransferase."}
{"id": "PMID:235313", "title": "Raman studies of the conformation of the basic pancreatic trypsin inhibitor.", "content": "The vibrational Raman spectra of the basic pancreatic trypsin inhibitor in aqueous solution, as lyophilized powder and in a single crystal and presented. The thermal stability of this protein is demonstrated by the fact that minor alterations in the spectrum, mainly in the amide III band near 1260 cm-1, occur in the solution spectrum only at temperatures above 75 degrees C. No significant spectral changes appear when the pH value of the solution is varied in the range from 1.5 to 8.7. The distinct differences of the powder spectrum compared to that of the solution, show that lyophilization causes appreciable conformational changes both in the main-chain and in the side-chains. A difference in main chain conformation of the basic pancreatic trypsin inhibitor in single crystal and in solution is suggested by different amide III frequencies.", "contents": "Raman studies of the conformation of the basic pancreatic trypsin inhibitor. The vibrational Raman spectra of the basic pancreatic trypsin inhibitor in aqueous solution, as lyophilized powder and in a single crystal and presented. The thermal stability of this protein is demonstrated by the fact that minor alterations in the spectrum, mainly in the amide III band near 1260 cm-1, occur in the solution spectrum only at temperatures above 75 degrees C. No significant spectral changes appear when the pH value of the solution is varied in the range from 1.5 to 8.7. The distinct differences of the powder spectrum compared to that of the solution, show that lyophilization causes appreciable conformational changes both in the main-chain and in the side-chains. A difference in main chain conformation of the basic pancreatic trypsin inhibitor in single crystal and in solution is suggested by different amide III frequencies."}
{"id": "PMID:235314", "title": "Structural and functional determinants of Mucor miehei protease. V. Enthalpy changes upon thermal denaturation in solution of varying pH.", "content": "The thermal denaturation of Mucor meihei protease was studied as a function of pH by differential scanning calorimetry. In both citric acid-Na2HPO4 and in acetic acid-sodium acetate buffers, maximum thermal stability was at pH 4.0-4.2. However, the maximum enthalpy changes associated with the denaturation process were buffer-dependent and occurred between pH values of 4.7 and 5.7.", "contents": "Structural and functional determinants of Mucor miehei protease. V. Enthalpy changes upon thermal denaturation in solution of varying pH. The thermal denaturation of Mucor meihei protease was studied as a function of pH by differential scanning calorimetry. In both citric acid-Na2HPO4 and in acetic acid-sodium acetate buffers, maximum thermal stability was at pH 4.0-4.2. However, the maximum enthalpy changes associated with the denaturation process were buffer-dependent and occurred between pH values of 4.7 and 5.7."}
{"id": "PMID:235315", "title": "Analysis of bacterial biotin-proteins.", "content": "The biotin-protein populations in several bacterial strains were analyzed by solubilization of [3H]biotin-labeled cells with sodium dodecylsulfate followed by electrophoresis on polyacrylamide gels containing the detergent. A variety of patterns of biotin-labeled polypeptide chains was seen, ranging from a single biotin-protein in Escherichia coli, corresponding to the biotin carboxyl carrier protein component of acetyl-CoA carboxylase, to multiple species in Enterobacter aerogenes, Pseudomonas citronellolis, Bacillus cereus, Propionibacterium shermanii, Lactobacillus plantarum, and Mycobacterium phlei, which probably represent subunits of multiple biotin-dependent enzymes present in these organisms. In the case of Pseudomonas citronellolis two major biotin-containing polypeptides with approximate molecular weights of 65 000 and 25 000 were shown to correspond to the biotin carboxyl carrier components of pyruvate carboxylase and acetyl-CoA carboxylase, respectively. Thus in the case of Pseudomonas citronellolis two different biotin-dependent enzymes in the same cell do not share common biotin carboxyl carrier subunits.", "contents": "Analysis of bacterial biotin-proteins. The biotin-protein populations in several bacterial strains were analyzed by solubilization of [3H]biotin-labeled cells with sodium dodecylsulfate followed by electrophoresis on polyacrylamide gels containing the detergent. A variety of patterns of biotin-labeled polypeptide chains was seen, ranging from a single biotin-protein in Escherichia coli, corresponding to the biotin carboxyl carrier protein component of acetyl-CoA carboxylase, to multiple species in Enterobacter aerogenes, Pseudomonas citronellolis, Bacillus cereus, Propionibacterium shermanii, Lactobacillus plantarum, and Mycobacterium phlei, which probably represent subunits of multiple biotin-dependent enzymes present in these organisms. In the case of Pseudomonas citronellolis two major biotin-containing polypeptides with approximate molecular weights of 65 000 and 25 000 were shown to correspond to the biotin carboxyl carrier components of pyruvate carboxylase and acetyl-CoA carboxylase, respectively. Thus in the case of Pseudomonas citronellolis two different biotin-dependent enzymes in the same cell do not share common biotin carboxyl carrier subunits."}
{"id": "PMID:235316", "title": "The location of protein in serum lipoproteins: a fluorescence quenching study.", "content": "Quenching of the tryptophan fluorescence of pig serum HDL3 and LDL2 lipoproteins by iodide and succinimide has been used to estimate the accessibility of the fluorophores to the solvent and, by inference, the location of the protein in the macromolecular complexes. At least 80% of the protein is thought to be located at or near the surface in both lipoproteins but its accessibility is hindered especially in LDL2. A difference in surface topography in the two lipoproteins is suggested with the protein in LDL2 more buried in lipid and further away from the charged phospholipid polar groups than in HDL3. A refined treatment of the quenching data has been developed to take account of the heterogeneity of quenching sites found in the lipoproteins.", "contents": "The location of protein in serum lipoproteins: a fluorescence quenching study. Quenching of the tryptophan fluorescence of pig serum HDL3 and LDL2 lipoproteins by iodide and succinimide has been used to estimate the accessibility of the fluorophores to the solvent and, by inference, the location of the protein in the macromolecular complexes. At least 80% of the protein is thought to be located at or near the surface in both lipoproteins but its accessibility is hindered especially in LDL2. A difference in surface topography in the two lipoproteins is suggested with the protein in LDL2 more buried in lipid and further away from the charged phospholipid polar groups than in HDL3. A refined treatment of the quenching data has been developed to take account of the heterogeneity of quenching sites found in the lipoproteins."}
{"id": "PMID:235318", "title": "Cationic proteins from human neutrophil granulocytes. Evidence for their chymotrypsin-like properties.", "content": "Three cationic proteins from the granules of human neutrophil granulocytes were obtained in a high degree of purity be means of affinity chromatography on 4-phenylbutylamine-Sepharose. Together with lysozyme, the three cationic proteins exhibit the highest electrophoretic mobility toward the cathode in acrylamide gels at moderately acid pH, among the granule constituents that are solubilized in 0.1 M phosphate buffer, pH 7.0, containing 1 M NaCl. The three cationic proteins represent a group of \"neutral proteases\" distinct from elastase and collagenase. They hydrolyze casein, azocasein and the chymotrypsin substrate N-acetyl-L-tyrosine ethyl ester. Optimal activity is found at pH 7.4-7;5. The enzymes are inhibited by the specific chymotrypsin inhibitor N-tosyl-L-phenylalanylchloromethane and by the naturally occurring inhibitors alpha-antichymotrypsin, alpha-1-antitrypsin, as well as by the trypsin inhibitors from soy beans and limabeans.", "contents": "Cationic proteins from human neutrophil granulocytes. Evidence for their chymotrypsin-like properties. Three cationic proteins from the granules of human neutrophil granulocytes were obtained in a high degree of purity be means of affinity chromatography on 4-phenylbutylamine-Sepharose. Together with lysozyme, the three cationic proteins exhibit the highest electrophoretic mobility toward the cathode in acrylamide gels at moderately acid pH, among the granule constituents that are solubilized in 0.1 M phosphate buffer, pH 7.0, containing 1 M NaCl. The three cationic proteins represent a group of \"neutral proteases\" distinct from elastase and collagenase. They hydrolyze casein, azocasein and the chymotrypsin substrate N-acetyl-L-tyrosine ethyl ester. Optimal activity is found at pH 7.4-7;5. The enzymes are inhibited by the specific chymotrypsin inhibitor N-tosyl-L-phenylalanylchloromethane and by the naturally occurring inhibitors alpha-antichymotrypsin, alpha-1-antitrypsin, as well as by the trypsin inhibitors from soy beans and limabeans."}
{"id": "PMID:235319", "title": "A conformational change in bovine beta-lactoglobulin at low pH.", "content": "A conformational change at low pH in bovine beta-lactoglobulin A has been studied by intrinsic fluorescence and fluorescence of the bound dye 8-anilinonaphthalene-1-sulphonate. Both studies show that when the pH of beta-lactoglobulin solutions is altered between 6.5 and 2.0, a rapid change in protein conformation occurs, followed by a slower conformational change. It seems likely that the rapid changes are linked with the predominance of protein dimer at pH 6.5 and monomer at pH 2.0. The slow changes involve shifts in protein conformation of the region that includes one of the protein tryptophan residues.", "contents": "A conformational change in bovine beta-lactoglobulin at low pH. A conformational change at low pH in bovine beta-lactoglobulin A has been studied by intrinsic fluorescence and fluorescence of the bound dye 8-anilinonaphthalene-1-sulphonate. Both studies show that when the pH of beta-lactoglobulin solutions is altered between 6.5 and 2.0, a rapid change in protein conformation occurs, followed by a slower conformational change. It seems likely that the rapid changes are linked with the predominance of protein dimer at pH 6.5 and monomer at pH 2.0. The slow changes involve shifts in protein conformation of the region that includes one of the protein tryptophan residues."}
{"id": "PMID:235320", "title": "Lipoprotein lipase in rat lung. The effect of fasting.", "content": "We measured lipoprotein lipase activity in dried defatted preparations of rat lung using doubly labeled chylomicron triglyceride as substrate. The enzyme activity was linear for the first hour of incubation at 37 degrees C, had a pH optimum of 8.1 and was completely inhibited by 0.5 M NaC1. Lungs from fed rats hydrolyzed chylomicron triglyceride at a rate of 13.00 mumoles/g per h; the activity rate was unchanged by fasting 8-72 h. Heparin infusion into isolated lungs caused immediate release of lipoprotein lipase to the venous effluent. The activity released was equivalent to about 10% of total lung lipoprotein lipase activity in both fed and fasted rats. Since the ability to remove blood triglyceride is directly related to the level of lipoprotein lipase activity, these findings indicate that the lung is one of the few tissues able to remove efficiently blood triglyceride during fasting.", "contents": "Lipoprotein lipase in rat lung. The effect of fasting. We measured lipoprotein lipase activity in dried defatted preparations of rat lung using doubly labeled chylomicron triglyceride as substrate. The enzyme activity was linear for the first hour of incubation at 37 degrees C, had a pH optimum of 8.1 and was completely inhibited by 0.5 M NaC1. Lungs from fed rats hydrolyzed chylomicron triglyceride at a rate of 13.00 mumoles/g per h; the activity rate was unchanged by fasting 8-72 h. Heparin infusion into isolated lungs caused immediate release of lipoprotein lipase to the venous effluent. The activity released was equivalent to about 10% of total lung lipoprotein lipase activity in both fed and fasted rats. Since the ability to remove blood triglyceride is directly related to the level of lipoprotein lipase activity, these findings indicate that the lung is one of the few tissues able to remove efficiently blood triglyceride during fasting."}
{"id": "PMID:235321", "title": "A possible mechanism for the peroxidation of lipids due to chronic ethanol ingestion.", "content": "The effects of chronic ethanol ingestion on NADPH-oxidase and on the NADPH-catalyzed peroxidation of lipids in rat liver microsomes have been studied. It was demonstrated that the rates of NADPH oxidation, of oxygen consumption, and of malondialdehyde formation increased significantly above control values after one month of ethanol ingestion. Further, the fatty acid composition of these microsomes revealed a decrease in arachidonate and in the C22 polyenes. Also, the energies of activation for the formation of malondialdehyde increased in the microsomes from the ethanol-treated animals. These results were interpreted to mean that ethanol ingestion had induced changes in the microsomal membranes such that additional or alternate, possibly abnormal, pathways for lipid peroxidation were functional. Finally, these data suggest a mechanism whereby chronic ethanol ingestion inhances the production of lipid peroxides via the microsomal-catalyzed oxidation of NADPH.", "contents": "A possible mechanism for the peroxidation of lipids due to chronic ethanol ingestion. The effects of chronic ethanol ingestion on NADPH-oxidase and on the NADPH-catalyzed peroxidation of lipids in rat liver microsomes have been studied. It was demonstrated that the rates of NADPH oxidation, of oxygen consumption, and of malondialdehyde formation increased significantly above control values after one month of ethanol ingestion. Further, the fatty acid composition of these microsomes revealed a decrease in arachidonate and in the C22 polyenes. Also, the energies of activation for the formation of malondialdehyde increased in the microsomes from the ethanol-treated animals. These results were interpreted to mean that ethanol ingestion had induced changes in the microsomal membranes such that additional or alternate, possibly abnormal, pathways for lipid peroxidation were functional. Finally, these data suggest a mechanism whereby chronic ethanol ingestion inhances the production of lipid peroxides via the microsomal-catalyzed oxidation of NADPH."}
{"id": "PMID:235322", "title": "The biosynthesis of plasmalogens by rat brain: involvement of the microsomal electron transport system.", "content": "The biosynthesis of 1-alk-1'-enyl-2-acyl-sn-glycero-3-phosphoethanolamine (ethanolamine plasmalogens) was studied using 1-[1-14C]hexadecyl-sn-glycero-3-phosphoethanolamine as the substrate and EDTA-washed microsomes from brains of 14-day-old rats. It was found that the 1-E11-14C]hexadecyl-sn-glycero-3-phosphoethanolamine was first acylated to form 1-[1-14C]hexadecyl-2-acyl-sn-glycero-3-phosphoethanolamine, then was desaturated to form 1-[1-14C]hexadec-1'-enyl-2-acyl-sn-glycero-3-phosphoethanolamine. The desaturation required O2 and NADH or NADPH and was inhibited by KCN but not by CO. The data indicated that the desaturation is carried out by a mixed-function oxidase system similar to that involved in the desaturation of fatty acids and that the pathway for the biosynthesis of plasmalogens in brain is similar to that previously found in other tissues. The desaturase was not stimulated by ATP and Mg2plus nor inhibited by EDTA. The specific activity of microsomes from brains of rats of different ages was determined; the activity decreased with age until in adults the activity was only 15% that of the 12--14-day-old rats.", "contents": "The biosynthesis of plasmalogens by rat brain: involvement of the microsomal electron transport system. The biosynthesis of 1-alk-1'-enyl-2-acyl-sn-glycero-3-phosphoethanolamine (ethanolamine plasmalogens) was studied using 1-[1-14C]hexadecyl-sn-glycero-3-phosphoethanolamine as the substrate and EDTA-washed microsomes from brains of 14-day-old rats. It was found that the 1-E11-14C]hexadecyl-sn-glycero-3-phosphoethanolamine was first acylated to form 1-[1-14C]hexadecyl-2-acyl-sn-glycero-3-phosphoethanolamine, then was desaturated to form 1-[1-14C]hexadec-1'-enyl-2-acyl-sn-glycero-3-phosphoethanolamine. The desaturation required O2 and NADH or NADPH and was inhibited by KCN but not by CO. The data indicated that the desaturation is carried out by a mixed-function oxidase system similar to that involved in the desaturation of fatty acids and that the pathway for the biosynthesis of plasmalogens in brain is similar to that previously found in other tissues. The desaturase was not stimulated by ATP and Mg2plus nor inhibited by EDTA. The specific activity of microsomes from brains of rats of different ages was determined; the activity decreased with age until in adults the activity was only 15% that of the 12--14-day-old rats."}
{"id": "PMID:235323", "title": "The inhibition by bromothymol blue of anion translocation across the mitochondrial membrane.", "content": "1. In rat liver mitochondria bromothymol blue inhibited the exchange of [14C]succinate for succinate, malonate, L-malate and inorganic phosphate; the [14C]citrate/citrate and [14C]citrate/malate exchange reactions and the phosphate/hydroxyl exchange were also inhibited by this dye. The inhibition of the rate of succinate, citrate and phosphate uptake by bromothymol blue is found to be competitive. 2. The degree of inhibition by bromothymol blue of the ]14C]succinate/malonate exchange reaction was pH dependent. It has been shown that the inhibition increased linearly while the pH was increased from 6.0 to 8.2. However, the binding rate of bromothymol blue to the mitochondria decreased with the rising pH of the medium. It is concluded that the binding of acidic bromothymol blue was not essential for the inhibitory effect. 3. Other sulfonephthalein derivatives also inhibited [14C]succinate/malonate exchange reaction. At pH 7.2 the relative order of the strength of the inhibitory action of the sulfonephthalein compounds tested was: thymol blue greater than bronocresol green greater than bromothymol blue greater than phenol red greater than bromocresol purple. The results do not indicate any correlation between the pK values of pH values of pH indicators and their extents of inhibition. 4. It is suggested that the negatively charged bromothymol blue interacts with the positively charged centers of the anion carrier systems causing inhibition of membrane permeability for anions.", "contents": "The inhibition by bromothymol blue of anion translocation across the mitochondrial membrane. 1. In rat liver mitochondria bromothymol blue inhibited the exchange of [14C]succinate for succinate, malonate, L-malate and inorganic phosphate; the [14C]citrate/citrate and [14C]citrate/malate exchange reactions and the phosphate/hydroxyl exchange were also inhibited by this dye. The inhibition of the rate of succinate, citrate and phosphate uptake by bromothymol blue is found to be competitive. 2. The degree of inhibition by bromothymol blue of the ]14C]succinate/malonate exchange reaction was pH dependent. It has been shown that the inhibition increased linearly while the pH was increased from 6.0 to 8.2. However, the binding rate of bromothymol blue to the mitochondria decreased with the rising pH of the medium. It is concluded that the binding of acidic bromothymol blue was not essential for the inhibitory effect. 3. Other sulfonephthalein derivatives also inhibited [14C]succinate/malonate exchange reaction. At pH 7.2 the relative order of the strength of the inhibitory action of the sulfonephthalein compounds tested was: thymol blue greater than bronocresol green greater than bromothymol blue greater than phenol red greater than bromocresol purple. The results do not indicate any correlation between the pK values of pH values of pH indicators and their extents of inhibition. 4. It is suggested that the negatively charged bromothymol blue interacts with the positively charged centers of the anion carrier systems causing inhibition of membrane permeability for anions."}
{"id": "PMID:235324", "title": "Electromechanical stresses and the effect of pH on membrane structure.", "content": "The presence of an electric field in a membrane creates stresses which lead to a mechanical compression of the membrane material. It is shown that considerations of this effect yield results consistent with the observed differential effect of pH on the plasma membrane substructure if the central electron-lucent layer in OsO4-fixed membranes is identified with the ionic depletion in the double-fixed charge model of cell membranes.", "contents": "Electromechanical stresses and the effect of pH on membrane structure. The presence of an electric field in a membrane creates stresses which lead to a mechanical compression of the membrane material. It is shown that considerations of this effect yield results consistent with the observed differential effect of pH on the plasma membrane substructure if the central electron-lucent layer in OsO4-fixed membranes is identified with the ionic depletion in the double-fixed charge model of cell membranes."}
{"id": "PMID:235325", "title": "Enzymes of the human intestinal brush border membrane. Identification after gel electrophoretic separation.", "content": "The postition of a number of human intestine brush border membrane enzyme activities in polyacrylamide gels after electrophoresis has been determined. These activities are, in order from the origin, maltase/glucoamylase, lactase/phlorizin hydrolase, maltase/sucrase/isomaltase, enteropeptidase, trehalase and gamma-glutamyl-transferase. Leucylnaphthylamide hydrolyzing activity was inactivated by sodium dodecylsulfate and its position was not determined. The positions of the activities have been correlated with the positions of protein bands previously determined. One such band situated between enteropeptidase and alkaline phosphatase has not been identified.", "contents": "Enzymes of the human intestinal brush border membrane. Identification after gel electrophoretic separation. The postition of a number of human intestine brush border membrane enzyme activities in polyacrylamide gels after electrophoresis has been determined. These activities are, in order from the origin, maltase/glucoamylase, lactase/phlorizin hydrolase, maltase/sucrase/isomaltase, enteropeptidase, trehalase and gamma-glutamyl-transferase. Leucylnaphthylamide hydrolyzing activity was inactivated by sodium dodecylsulfate and its position was not determined. The positions of the activities have been correlated with the positions of protein bands previously determined. One such band situated between enteropeptidase and alkaline phosphatase has not been identified."}
{"id": "PMID:235326", "title": "Bicarbonate ion-ATPase in rat liver cell fractions.", "content": "The distribution of HCO3MINUS-ATPase activity was studied in cell fractions prepared from homogenates of rat liver. The level of mitochondrial contamination in the microsomal fraction depended on the fractionation procedure and on the method of homogenization. With proper care, microsomes with undetectable mitochondrial contamination could be prepared. These microsomes had no detectable HCO3MINUS-ATPase activity. Approximately 85% of the total HCO3minus-ATPase activity of the post 6000 times g-min supernatant was recovered in the mitochondrial fraction. The properties of this mitochondrial HCO3minus-ATPase were not distinguishable from those of the various microsomal HCO3minus-ATPases previously described by other investigators.", "contents": "Bicarbonate ion-ATPase in rat liver cell fractions. The distribution of HCO3MINUS-ATPase activity was studied in cell fractions prepared from homogenates of rat liver. The level of mitochondrial contamination in the microsomal fraction depended on the fractionation procedure and on the method of homogenization. With proper care, microsomes with undetectable mitochondrial contamination could be prepared. These microsomes had no detectable HCO3MINUS-ATPase activity. Approximately 85% of the total HCO3minus-ATPase activity of the post 6000 times g-min supernatant was recovered in the mitochondrial fraction. The properties of this mitochondrial HCO3minus-ATPase were not distinguishable from those of the various microsomal HCO3minus-ATPases previously described by other investigators."}
{"id": "PMID:235327", "title": "A calorimetric study of the helix-coil transition of poly(cytidylic acid) in acid solution.", "content": "In this study we show how the thermal stability of the helical structure of poly(C) is dependent on the degree of protonation. deltaH values for the thermal denaturation are measured directly by means of an adiabatic microcalorimeter in the pH range from pH 5.8 to 3.7. The maximum transition temperature T-m is found at pH 4.5 where poly(C) is semiprotonated. At the same pH value a maximum value of deltaH (deltaH equals 5.27 Kcal/mol base pairs) was obtained. deltaH decreases slightly if the pH changes to lower or higher pH values. No transition was observed either at pH 6.0 or at pH 3.4. The deltaGtheta(25 degrees C) values show a similar dependence on the degree of protonation of poly(C).", "contents": "A calorimetric study of the helix-coil transition of poly(cytidylic acid) in acid solution. In this study we show how the thermal stability of the helical structure of poly(C) is dependent on the degree of protonation. deltaH values for the thermal denaturation are measured directly by means of an adiabatic microcalorimeter in the pH range from pH 5.8 to 3.7. The maximum transition temperature T-m is found at pH 4.5 where poly(C) is semiprotonated. At the same pH value a maximum value of deltaH (deltaH equals 5.27 Kcal/mol base pairs) was obtained. deltaH decreases slightly if the pH changes to lower or higher pH values. No transition was observed either at pH 6.0 or at pH 3.4. The deltaGtheta(25 degrees C) values show a similar dependence on the degree of protonation of poly(C)."}
{"id": "PMID:235328", "title": "[A calorimetric study of the triple helix formation: interaction of poly(C) - guanosine - protonated poly(C)].", "content": "The triple helix formation of poly(C) - guanosine - poly(C+) was investigated by the help of an LKB scanning micro-calorimeter. The existence of the triple helix could also be shown by recording the melting curves. The ultraviolet absorption at different wave lengths namely 275 nm, 260 nm, and 245 nm was plotted as a function of the temperature. Furthermore formation of the triple helix was shown by plotting the ultraviolet absorption at 245 nm during the increasing addition of guanosine solution to a fixed amount of poly(C) in the solution. Finally the formation of the triple helix was demonstrated by plotting the ultraviolet absorption at 245 nm of a certain mixture of the components while the pH value of the solution was continuously lowered. All these methods show that the monomer interacts with the polymer double helix to form a triple helix. The calorimetric measurements show that the reaction enthalpy is concentration dependent. Above a threshold concentration a rapid increase of the reaction enthalpy is observed. This increase occurs in a very narrow concentration interval. Above this interval a final value of the reaction enthalpy is reached. The amount of the reaction enthalpy for the interaction of guanosine with poly(C) - poly(C+) double helix is 5.5 Kcal (mol base triplet)-1.", "contents": "[A calorimetric study of the triple helix formation: interaction of poly(C) - guanosine - protonated poly(C)]. The triple helix formation of poly(C) - guanosine - poly(C+) was investigated by the help of an LKB scanning micro-calorimeter. The existence of the triple helix could also be shown by recording the melting curves. The ultraviolet absorption at different wave lengths namely 275 nm, 260 nm, and 245 nm was plotted as a function of the temperature. Furthermore formation of the triple helix was shown by plotting the ultraviolet absorption at 245 nm during the increasing addition of guanosine solution to a fixed amount of poly(C) in the solution. Finally the formation of the triple helix was demonstrated by plotting the ultraviolet absorption at 245 nm of a certain mixture of the components while the pH value of the solution was continuously lowered. All these methods show that the monomer interacts with the polymer double helix to form a triple helix. The calorimetric measurements show that the reaction enthalpy is concentration dependent. Above a threshold concentration a rapid increase of the reaction enthalpy is observed. This increase occurs in a very narrow concentration interval. Above this interval a final value of the reaction enthalpy is reached. The amount of the reaction enthalpy for the interaction of guanosine with poly(C) - poly(C+) double helix is 5.5 Kcal (mol base triplet)-1."}
{"id": "PMID:235334", "title": "Near-ultraviolet light-induced strand breaks in DNA pretreated with the carcinogen, N-acetoxy-2-acetylaminofluorene.", "content": "Neutral sucrose gradients of supercoiled DNA (phiX-174 RF I) were used to measure the in vitro production of strand breaks by the carcinogen, N-acetoxy-2-acetylaminofluorene (AcO-AAF). Treatment with AcO-AAF in 10% dimethyl sulfoxide did not directly yield strand breaks. Breaks in relatively low yield appeared after alkali treatment (pH 13, 60 min) of the RF I previously reacted with AcO-AAF. The DNA treated with AcO-AAF was sensitive to single-strand breakage by 303 nm near-ultraviolet light under neutral conditions. The greater the prior AcO-AAF treatment, the greater the sensitivity to 303 nm light. Post-irradiation alkali treatment greatly enhanced the light-induced strand breakage.", "contents": "Near-ultraviolet light-induced strand breaks in DNA pretreated with the carcinogen, N-acetoxy-2-acetylaminofluorene. Neutral sucrose gradients of supercoiled DNA (phiX-174 RF I) were used to measure the in vitro production of strand breaks by the carcinogen, N-acetoxy-2-acetylaminofluorene (AcO-AAF). Treatment with AcO-AAF in 10% dimethyl sulfoxide did not directly yield strand breaks. Breaks in relatively low yield appeared after alkali treatment (pH 13, 60 min) of the RF I previously reacted with AcO-AAF. The DNA treated with AcO-AAF was sensitive to single-strand breakage by 303 nm near-ultraviolet light under neutral conditions. The greater the prior AcO-AAF treatment, the greater the sensitivity to 303 nm light. Post-irradiation alkali treatment greatly enhanced the light-induced strand breakage."}
{"id": "PMID:235335", "title": "Viscoelastic analysis of high molecular weight, alkali-denatured DNA from mouse 3T3 cells.", "content": "Alkaline lysates of mouse 3T3 cells showed viscoelastic properties characteristic of very large molecules of single-stranded DNA. The viscoelastic retardation time and the sensitivity to low doses of nitrogen mustard and of X-irradiation suggest a molecular weight in excess of 10-10 daltons. Contact-inhibited cells yielded larger single strands than actively growing cells.", "contents": "Viscoelastic analysis of high molecular weight, alkali-denatured DNA from mouse 3T3 cells. Alkaline lysates of mouse 3T3 cells showed viscoelastic properties characteristic of very large molecules of single-stranded DNA. The viscoelastic retardation time and the sensitivity to low doses of nitrogen mustard and of X-irradiation suggest a molecular weight in excess of 10-10 daltons. Contact-inhibited cells yielded larger single strands than actively growing cells."}
{"id": "PMID:235336", "title": "Long-term remission from acute myelogenous leukemia after bone marrow transplantation and recovery from acute graft-versus-host reaction and prolonged immunoincompetence.", "content": "A 19-yr-old boy has been in continuous complete remission from acute myelogenous leukemia for 3 yr after allogeneic bone marrow transplantation prepared with combination chemotherapy. During the first year post-transplant, however, the patient developed near-fatal graft-versus-host reaction followed by 11 severe viral and bacterial infections. Immune evaluation during this period revealed multiple defects which were not present prior to transplantation, nor present in the transplant donor: diminution of lymphoid tissue, decline of all immunoglobulin subtypes, deletion of secretory immunoglobulin, disappearance of isohemagglutinins, loss of antibody to diptheria and tetanus toxoids, cessation of cutaneous hypersensitivity to mumps antigen, and inhibition of serum opsonizing activity. The patient was also unable to develop normal humoral or cellular reactivity to brucella antigen, keyhole limpet hemocyanin, or dinitrochlorobenzene. This patient's course illustrates the severity and chronicity of immunoincompetence associated with allogeneic marrow grafting, the importance of early detection and rigorous treatment of infectious disease in these patients, and the need for improved immunologic reconstitution in human marrow transplantation. It also indicates that complete recovery from the immune defects is possible, and that long-term remission from acute myelogenous leukemia can be achieved with allogeneic marrow transplantation.", "contents": "Long-term remission from acute myelogenous leukemia after bone marrow transplantation and recovery from acute graft-versus-host reaction and prolonged immunoincompetence. A 19-yr-old boy has been in continuous complete remission from acute myelogenous leukemia for 3 yr after allogeneic bone marrow transplantation prepared with combination chemotherapy. During the first year post-transplant, however, the patient developed near-fatal graft-versus-host reaction followed by 11 severe viral and bacterial infections. Immune evaluation during this period revealed multiple defects which were not present prior to transplantation, nor present in the transplant donor: diminution of lymphoid tissue, decline of all immunoglobulin subtypes, deletion of secretory immunoglobulin, disappearance of isohemagglutinins, loss of antibody to diptheria and tetanus toxoids, cessation of cutaneous hypersensitivity to mumps antigen, and inhibition of serum opsonizing activity. The patient was also unable to develop normal humoral or cellular reactivity to brucella antigen, keyhole limpet hemocyanin, or dinitrochlorobenzene. This patient's course illustrates the severity and chronicity of immunoincompetence associated with allogeneic marrow grafting, the importance of early detection and rigorous treatment of infectious disease in these patients, and the need for improved immunologic reconstitution in human marrow transplantation. It also indicates that complete recovery from the immune defects is possible, and that long-term remission from acute myelogenous leukemia can be achieved with allogeneic marrow transplantation."}
{"id": "PMID:235337", "title": "Abnormal red cell metabolism in patients with chronic uremia: Nature of the defect and its persistence despite adequate hemodialysis.", "content": "A red cell metabolic abnormality, which diminishes the maximum activity of the pentose phosphate shunt, occurs in some uremic patients, even those adequately dialyzed with fluids prepared from distilled or charcoal-filtered water. Within individual patients the severity of this abnormality does not change even after 9 mo of consecutive hemodialyses. However, between patients it does correlate inversely with hematocrit. When erythrocytes from patients with the abnormality are stressed with oxidant compounds, such as ascorbate, erythrocyte glucose consumption and lactate formation are abnormally increased, while lactate/pyruvate ratios abnormally diminish. Concomitantly, red cell glycolytic intermediates, including fructose-1,6-diphosphate, glyceraldehyde-3-phosphate, 3-phosphoglycerate, phosphoenol pyruvate, and pyruvate, markedly accumulate. Surprisingly, no increase of 2-phosphoglycerate occurs, which suggests that inefficient phosphoglyceromutase activity underlies this perturbation of erythrocyte metabolism and its associated hemolytic process.", "contents": "Abnormal red cell metabolism in patients with chronic uremia: Nature of the defect and its persistence despite adequate hemodialysis. A red cell metabolic abnormality, which diminishes the maximum activity of the pentose phosphate shunt, occurs in some uremic patients, even those adequately dialyzed with fluids prepared from distilled or charcoal-filtered water. Within individual patients the severity of this abnormality does not change even after 9 mo of consecutive hemodialyses. However, between patients it does correlate inversely with hematocrit. When erythrocytes from patients with the abnormality are stressed with oxidant compounds, such as ascorbate, erythrocyte glucose consumption and lactate formation are abnormally increased, while lactate/pyruvate ratios abnormally diminish. Concomitantly, red cell glycolytic intermediates, including fructose-1,6-diphosphate, glyceraldehyde-3-phosphate, 3-phosphoglycerate, phosphoenol pyruvate, and pyruvate, markedly accumulate. Surprisingly, no increase of 2-phosphoglycerate occurs, which suggests that inefficient phosphoglyceromutase activity underlies this perturbation of erythrocyte metabolism and its associated hemolytic process."}
{"id": "PMID:235338", "title": "Fibrinogen \"\"New York\"--an abnormal fibrinogen associated with thromboembolism: functional evaluation.", "content": "A 54-yr-old woman presented with a 23-yr history of repeated life-threatening thromboembolism. The presence of a qualitatively abnormal fibrinogen was suggested by the demonstration of delayed and incomplete coagulation of plasma or partially purified fibrinogen by thrombin or Reptilase. Two brothers showed a similar in vitro defect but were clinically not affected. The plasma fibrinogen concentration was 0.50-1.64 mg/ml when estimated by heat turbidity, clottability, or immunologic techniques. The serum contained 80-820 mug/ml of unclottable fibrinogen-related materials even after 24 hr exposure to thrombin. The fibrinogen-related material in the serum showed faster anodal mobility an immunoelectrophoresis than that of normal plasma. Immunodiffusion studies with rabbit antihuman fibrinogen antiserum showed lines of identity between control plasma and the patient's plasma and serum. Studies of the kinetics of thrombin action on fibrinogen demonstrated impaired release of fibrinopeptide A and B and defective polymerization of preformed fibrin monomers. The maximum amount of fibrinopeptide A released by exhaustive treatment with thrombin was similar (per milligram protein) for both the patient's and control fibrinogen. This abnormal fibrinogen varient is tentatively designated fibrinogen \"New York\"; its possible identity with one of the previously described abnormal fibrinogens has not been excluded.", "contents": "Fibrinogen \"\"New York\"--an abnormal fibrinogen associated with thromboembolism: functional evaluation. A 54-yr-old woman presented with a 23-yr history of repeated life-threatening thromboembolism. The presence of a qualitatively abnormal fibrinogen was suggested by the demonstration of delayed and incomplete coagulation of plasma or partially purified fibrinogen by thrombin or Reptilase. Two brothers showed a similar in vitro defect but were clinically not affected. The plasma fibrinogen concentration was 0.50-1.64 mg/ml when estimated by heat turbidity, clottability, or immunologic techniques. The serum contained 80-820 mug/ml of unclottable fibrinogen-related materials even after 24 hr exposure to thrombin. The fibrinogen-related material in the serum showed faster anodal mobility an immunoelectrophoresis than that of normal plasma. Immunodiffusion studies with rabbit antihuman fibrinogen antiserum showed lines of identity between control plasma and the patient's plasma and serum. Studies of the kinetics of thrombin action on fibrinogen demonstrated impaired release of fibrinopeptide A and B and defective polymerization of preformed fibrin monomers. The maximum amount of fibrinopeptide A released by exhaustive treatment with thrombin was similar (per milligram protein) for both the patient's and control fibrinogen. This abnormal fibrinogen varient is tentatively designated fibrinogen \"New York\"; its possible identity with one of the previously described abnormal fibrinogens has not been excluded."}
{"id": "PMID:235340", "title": "Pharmacological receptors of the cerebral arteries of the goat.", "content": "5-Hydroxytryptamine (5-HT), norepinephrine (NE), histamine (H) and potassium (K+) chloride induce dose-dependent changes in tension of the isolated middle crerbral artery of the goat. Vasopressin produces highly variable responses followed by tachyphylaxis; angiotensin II is ineffective over a wide dose range. The order of potencies of these vasoactive agents is 5-HT greater than NE greater than H greater than K+. With regard to their ability to induce maximal contractile responses, the order is: H greater than 5-HT, K+ greater than NE. Lysergic acid diethylamide (LSD) antagonizes the actions of 5-HT in a manner which progresses from surmountability to unsurmountability of the blockade depending on the concentration of LSD. The blockade exerted by LSD is reversed by washing. Phentolamine and diphenhydramine competitively antagonize the actions of NE and H, respectively. The potency of phentolamine and diphenhydramine in the cerebral arteries of the goat is similar to that determined in different tissues obtained from a variety of animal species. It is concluded that the cerebral arteries of the goat possess receptors for biogenic amines, the most effective of which is 5-HT; receptors for vasoactive peptides are ill defined.?25", "contents": "Pharmacological receptors of the cerebral arteries of the goat. 5-Hydroxytryptamine (5-HT), norepinephrine (NE), histamine (H) and potassium (K+) chloride induce dose-dependent changes in tension of the isolated middle crerbral artery of the goat. Vasopressin produces highly variable responses followed by tachyphylaxis; angiotensin II is ineffective over a wide dose range. The order of potencies of these vasoactive agents is 5-HT greater than NE greater than H greater than K+. With regard to their ability to induce maximal contractile responses, the order is: H greater than 5-HT, K+ greater than NE. Lysergic acid diethylamide (LSD) antagonizes the actions of 5-HT in a manner which progresses from surmountability to unsurmountability of the blockade depending on the concentration of LSD. The blockade exerted by LSD is reversed by washing. Phentolamine and diphenhydramine competitively antagonize the actions of NE and H, respectively. The potency of phentolamine and diphenhydramine in the cerebral arteries of the goat is similar to that determined in different tissues obtained from a variety of animal species. It is concluded that the cerebral arteries of the goat possess receptors for biogenic amines, the most effective of which is 5-HT; receptors for vasoactive peptides are ill defined.?25"}
{"id": "PMID:235344", "title": "Gamma-glutamyl transpeptidase, triglycerides, and enzyme induction.", "content": "A study conducted on 109 consecutive patients submitted for routine lipid and lipoprotein screening has shown a significant positive association between serum gamma-glutamyl transpeptidase (gamma-GT) activity and the serum triglyceride concentration and between serum gamma-GT activity and the serum pre-beta-lipoprotein concentration. We suggest that these associations may reflect hepatic microsomal enzyme induction in hyperlipidaemic subjects which increases the hepatic content of the rate-limiting enzyme(s) for triglyceride synthesis.", "contents": "Gamma-glutamyl transpeptidase, triglycerides, and enzyme induction. A study conducted on 109 consecutive patients submitted for routine lipid and lipoprotein screening has shown a significant positive association between serum gamma-glutamyl transpeptidase (gamma-GT) activity and the serum triglyceride concentration and between serum gamma-GT activity and the serum pre-beta-lipoprotein concentration. We suggest that these associations may reflect hepatic microsomal enzyme induction in hyperlipidaemic subjects which increases the hepatic content of the rate-limiting enzyme(s) for triglyceride synthesis."}
{"id": "PMID:235345", "title": "Gamma-aminobutric acid and glutamate decarboxylas (l-glutamate 1-carboxy-lyase e.c. 4.1.1.15) in the nervous system of the cockroach, periplaneta americana.i.regional distribution and properties of the enzyme.", "content": "Both the central and peripheral nervous system of the cockroach Periplaneta americana contain gamma-aminobutyric acid (GABA) and glutamate decarboxylase (GAD). In the central ganglia of the cockroach, an average of more that 60 mumoles of GABA are formed from glutamate (Glu) per gram wet weight of tissue per hour. This activity level of the GAD apoenzyme is considerably higher than that found in the central nervous system of crustaceans, amphibians, avians and mammals but is similar to that reported for nervous system tissues from other insect species. A comparison of properties of the crude cockroach enzyme with GAD from crustacean and mammalian origin revealed both similarities and differences: whereas crude cockroach GAD has cofactor requirements and an affinity for Glu substrate (Km 2.8 X 10-2) which are similar to GAD from lobster and mouse, it is uniquely inhibited by both Cl-and by GABA. The GAD from cockroach nervous tissues has two apparent pH optima of which the lower one is preferentially inhibited by a compound which is found in the nerve sheath and the fat body tissue adjacent to ganglia and axons.", "contents": "Gamma-aminobutric acid and glutamate decarboxylas (l-glutamate 1-carboxy-lyase e.c. 4.1.1.15) in the nervous system of the cockroach, periplaneta americana.i.regional distribution and properties of the enzyme. Both the central and peripheral nervous system of the cockroach Periplaneta americana contain gamma-aminobutyric acid (GABA) and glutamate decarboxylase (GAD). In the central ganglia of the cockroach, an average of more that 60 mumoles of GABA are formed from glutamate (Glu) per gram wet weight of tissue per hour. This activity level of the GAD apoenzyme is considerably higher than that found in the central nervous system of crustaceans, amphibians, avians and mammals but is similar to that reported for nervous system tissues from other insect species. A comparison of properties of the crude cockroach enzyme with GAD from crustacean and mammalian origin revealed both similarities and differences: whereas crude cockroach GAD has cofactor requirements and an affinity for Glu substrate (Km 2.8 X 10-2) which are similar to GAD from lobster and mouse, it is uniquely inhibited by both Cl-and by GABA. The GAD from cockroach nervous tissues has two apparent pH optima of which the lower one is preferentially inhibited by a compound which is found in the nerve sheath and the fat body tissue adjacent to ganglia and axons."}
{"id": "PMID:235346", "title": "Studies on  bursting pacemaker potential activity in molluscan neurons. II. Regulations by divalanet cations.", "content": "Identified cells in Aplysia (R15, R2, LPG) and cell 11 in Otala have been used to investigate the effects of divalent cations, temperature, pH and ouabain on neuronal activity. Divalent cations act primarily to regulate the appearance of bursting pacemaker potential (BPP) activity in these cells. These ions are necessary for B generation and will inhibit its appearance at high concentrations (Ca greater than Mg greater that greater than Sr). In addition, Ca is involved in the seasonal modulation of BPP activity in a neurosecretory cell in Otala. Monovalent cations play secondary roles as regulators of BPP activity by competing with divalent cations for the sites involved in the regulation of the (probable) monovalent conductances underlying BPPs. The effects of pH, temperature and ouabain on membrane properties and BPP activity are partly related to their interaction with divalent cations. The results described indicate important roles for divalent cations in the regulation of the expression of BPP activity and its underlying membrane properties both in different nerve cells and in the same cell during dormancy and activity of the snails.", "contents": "Studies on  bursting pacemaker potential activity in molluscan neurons. II. Regulations by divalanet cations. Identified cells in Aplysia (R15, R2, LPG) and cell 11 in Otala have been used to investigate the effects of divalent cations, temperature, pH and ouabain on neuronal activity. Divalent cations act primarily to regulate the appearance of bursting pacemaker potential (BPP) activity in these cells. These ions are necessary for B generation and will inhibit its appearance at high concentrations (Ca greater than Mg greater that greater than Sr). In addition, Ca is involved in the seasonal modulation of BPP activity in a neurosecretory cell in Otala. Monovalent cations play secondary roles as regulators of BPP activity by competing with divalent cations for the sites involved in the regulation of the (probable) monovalent conductances underlying BPPs. The effects of pH, temperature and ouabain on membrane properties and BPP activity are partly related to their interaction with divalent cations. The results described indicate important roles for divalent cations in the regulation of the expression of BPP activity and its underlying membrane properties both in different nerve cells and in the same cell during dormancy and activity of the snails."}
{"id": "PMID:235351", "title": "A simple chromatographic method for the determination of the methylated basic amino acids in proteins.", "content": "A chromatographic method is described for the determination of epsilon-N-monomethyl-epsilon-N, epsilon-N-dimethyl-, and epsilon-N, epsilon-N, epsilon-N-trimethyllysines, 1-methyl-, and 3-methylhistidines, N-G, N-G-dimethyl-, and N-G, N'G-dimethylarginines, ornithine, the diastereoisomers of hydroxylysine, basic amino acids and related compounds, using Durrum type DC-6A 11.0 plus or minus 1.0 mum spherical resin. The complete separation of all of these amino acids as discrete peaks in the Beckman 120B amino acid analyzer was achieved for the first time using a single column (60 times 0.9 cm), one buffer system (0.35 N sodium citrate) adjusted at either pH 5.734 or 5.657 plus or minus 0.002, one buffer flow rate (30 ml/h), and one temperature (28 degrees C). This procedure was used for the analysis of these unusual amino acids in protein hydrolysates of histones and collagen and be applied to the determination of these compounds in hydrolysates of plant and animal tissues.", "contents": "A simple chromatographic method for the determination of the methylated basic amino acids in proteins. A chromatographic method is described for the determination of epsilon-N-monomethyl-epsilon-N, epsilon-N-dimethyl-, and epsilon-N, epsilon-N, epsilon-N-trimethyllysines, 1-methyl-, and 3-methylhistidines, N-G, N-G-dimethyl-, and N-G, N'G-dimethylarginines, ornithine, the diastereoisomers of hydroxylysine, basic amino acids and related compounds, using Durrum type DC-6A 11.0 plus or minus 1.0 mum spherical resin. The complete separation of all of these amino acids as discrete peaks in the Beckman 120B amino acid analyzer was achieved for the first time using a single column (60 times 0.9 cm), one buffer system (0.35 N sodium citrate) adjusted at either pH 5.734 or 5.657 plus or minus 0.002, one buffer flow rate (30 ml/h), and one temperature (28 degrees C). This procedure was used for the analysis of these unusual amino acids in protein hydrolysates of histones and collagen and be applied to the determination of these compounds in hydrolysates of plant and animal tissues."}
{"id": "PMID:235353", "title": "Lipase and esterase formation by psychrophilic and mesophilic Acinetobacter species.", "content": "Acinetobacter O16, a psychrophilic species, produced extracellular lipase (measured by hydrolysis of olive oil, tributyrin, or beta-naphthyl laurate) when grown on a complex medium (peptone plus yeast extract). Most lipase was produced during the logarithmic phase of growth. Very little cell-bound lipase was formed. These cells also produced an esterase (measured by the hydrolysis of beta-naphthyl acetate). At first, all esterase was cell bound; significant amounts appeared in the external medium late in growth. Breaking the cells did not increase cell-bound lipase activity. After breaking of the cells, most of the cell-bound lipase and esterase activity was solubilized, even after very high speed centrifugation. No appreciable amounts of these enzymes were released by osmotic shock. Lipase formation was greatly affected by nutrient conditions. Lowering either the yeast extract of the peptone content of the normal complex medium lowered or abolished lipase formation. Esterase activity was lowered to a lesser extent. Cells growing in synthetic amino acid plus vitamin medium or in acid-hydrolyzed casein produced substantial amounts of esterase but no cell-free or cell-bound lipase. However, if sodium taurocholate was added to these media, lipase was produced. Greatest production occurred if a mixture of di- and poly-peptides was also present. Taurocholate also stimulated lipase production in the normal complex medium. Adding Tween 80 or ethanol to the normal complex medium inhibited lipase production. Sodium acetate, oleic acid, olive oil, or Tween 20 added to synthetic media did not affect lipase production. The psychrophile grew more quickly at 30 degrees C than at 15 or 20 degrees C but produced more lipase at the lower temperatures. Esterase production was about the same at 20 and 30 degrees C. A mesophilic Acinetobacter species produced the same amount of lipase and esterase at 20 and 30 degrees C. The best production of lipase by the psychrophile occurred in standing cultures.", "contents": "Lipase and esterase formation by psychrophilic and mesophilic Acinetobacter species. Acinetobacter O16, a psychrophilic species, produced extracellular lipase (measured by hydrolysis of olive oil, tributyrin, or beta-naphthyl laurate) when grown on a complex medium (peptone plus yeast extract). Most lipase was produced during the logarithmic phase of growth. Very little cell-bound lipase was formed. These cells also produced an esterase (measured by the hydrolysis of beta-naphthyl acetate). At first, all esterase was cell bound; significant amounts appeared in the external medium late in growth. Breaking the cells did not increase cell-bound lipase activity. After breaking of the cells, most of the cell-bound lipase and esterase activity was solubilized, even after very high speed centrifugation. No appreciable amounts of these enzymes were released by osmotic shock. Lipase formation was greatly affected by nutrient conditions. Lowering either the yeast extract of the peptone content of the normal complex medium lowered or abolished lipase formation. Esterase activity was lowered to a lesser extent. Cells growing in synthetic amino acid plus vitamin medium or in acid-hydrolyzed casein produced substantial amounts of esterase but no cell-free or cell-bound lipase. However, if sodium taurocholate was added to these media, lipase was produced. Greatest production occurred if a mixture of di- and poly-peptides was also present. Taurocholate also stimulated lipase production in the normal complex medium. Adding Tween 80 or ethanol to the normal complex medium inhibited lipase production. Sodium acetate, oleic acid, olive oil, or Tween 20 added to synthetic media did not affect lipase production. The psychrophile grew more quickly at 30 degrees C than at 15 or 20 degrees C but produced more lipase at the lower temperatures. Esterase production was about the same at 20 and 30 degrees C. A mesophilic Acinetobacter species produced the same amount of lipase and esterase at 20 and 30 degrees C. The best production of lipase by the psychrophile occurred in standing cultures."}
{"id": "PMID:235354", "title": "Partial purification and characterization of the lipase of a facultatively psychrophilic bacterium (Acinetobacter O16).", "content": "The extracellular lipase(s) of the psychrophile Acinetobacter O16 was studied. When the enzyme was precipitated by (NH4)2SO4 and passed through a Sephadex G200 column, two peaks of lipase activity appeared. The larger peak, which behaved like a substance of high molecular weight, being eluted in the void volume, was purified 250-fold over the crude enzyme (culture supernatant) by passage through a DEAE-Sephadex column. When the enzyme was applied to a DEAE-cellulose column it could not be eluted unless it had first been treated with the detergent Titon X 100. It is suggested that lipids or phospholipids make up an important part of the molecule. The activity of the crude and partly purified enzymes was studied in relation to pH and temperature optima. Lipases from the psychrophilic Acinetobacter O16 and from the mesophilic Acinetobacter O4 reacted in the same way to temperature. The crude enzyme from Acinetobacter O16 was more temperature-stable than the purified enzyme.", "contents": "Partial purification and characterization of the lipase of a facultatively psychrophilic bacterium (Acinetobacter O16). The extracellular lipase(s) of the psychrophile Acinetobacter O16 was studied. When the enzyme was precipitated by (NH4)2SO4 and passed through a Sephadex G200 column, two peaks of lipase activity appeared. The larger peak, which behaved like a substance of high molecular weight, being eluted in the void volume, was purified 250-fold over the crude enzyme (culture supernatant) by passage through a DEAE-Sephadex column. When the enzyme was applied to a DEAE-cellulose column it could not be eluted unless it had first been treated with the detergent Titon X 100. It is suggested that lipids or phospholipids make up an important part of the molecule. The activity of the crude and partly purified enzymes was studied in relation to pH and temperature optima. Lipases from the psychrophilic Acinetobacter O16 and from the mesophilic Acinetobacter O4 reacted in the same way to temperature. The crude enzyme from Acinetobacter O16 was more temperature-stable than the purified enzyme."}
{"id": "PMID:235355", "title": "California encephalitis virus development in mosquitoes as revealed by transmission studies, immunoperoxidase staining, and electron microscopy.", "content": "Isolates of the snowshoe hare subtype of California encephalitis (CE) virus from Yukon mosquitoes during 1972 and 1973 were transmitted by bites of Aedes aegypti mosquitoes after 4 to 5 weeks of extrinsic incubation at 55 degrees F after intrathoracic injection, and the 1973 strain was transmitted after mosquitoes were fed virus and held for 3 to 4 weeks at 75 degrees F. Antigen of a 1971 isolate of CE virus (Marsh Lake 23) was detected in salivary glands of infected mosquitoes by the immunoperoxidase technique, using highly purified antiserum before and after conjugation with horseradish peroxidase, plus the use of orthotolidine as a substitute for benzidine. enveloped virions 45 nm in diameter were observed in thin sections of salivary glands of Culiseta inornata mosquitoes 59 days after intrathoracic injection with the 1971 isolate, afterincubation at 55 degrees F.", "contents": "California encephalitis virus development in mosquitoes as revealed by transmission studies, immunoperoxidase staining, and electron microscopy. Isolates of the snowshoe hare subtype of California encephalitis (CE) virus from Yukon mosquitoes during 1972 and 1973 were transmitted by bites of Aedes aegypti mosquitoes after 4 to 5 weeks of extrinsic incubation at 55 degrees F after intrathoracic injection, and the 1973 strain was transmitted after mosquitoes were fed virus and held for 3 to 4 weeks at 75 degrees F. Antigen of a 1971 isolate of CE virus (Marsh Lake 23) was detected in salivary glands of infected mosquitoes by the immunoperoxidase technique, using highly purified antiserum before and after conjugation with horseradish peroxidase, plus the use of orthotolidine as a substitute for benzidine. enveloped virions 45 nm in diameter were observed in thin sections of salivary glands of Culiseta inornata mosquitoes 59 days after intrathoracic injection with the 1971 isolate, afterincubation at 55 degrees F."}
{"id": "PMID:235356", "title": "Rsistance to streptomycin in a producing strain of Streptomyces griseus.", "content": "Streptomyces griseus S 104 was sensitive to streptomycin during exponential growth in a medium which, in the subsequent stationary phase, supported production of the antibiotic in yields above 200 mug/ml. When antibiotic production began cultures developed a tolerance toward their lethal metabolite. This was not due to an increase in pH associated with antibiotic production, since pH effects on streptomycin sensitivity in S. griseus were in the reverse direction. However, the degree of tolerance was directly related to the amount of cell material present. Streptomycin production caused no change in the proportion of resistant variants in the population, nor did it cause the severe inhibition of protein synthesis observed in non-producing cultures exposed to the antibiotic. The lack of an effect on protein synthesis is attributed to the absence of streptomycin with in the cytoplasm since soluble extracts from mycelium harvested in the production phase were inactive when bioassayed immediately after cell disruption. However, they developed antibacterial activity rapidly when heated, and more slowly when incubated at 25 degrees C. The addition of phosphatase inhibitors during incubation prevented the appearance of antibiotic activity, and it was concluded that a small amount of streptomycin phosphate is present in the mycelium during antibiotic production. Differences in (14C) streptomycin uptake suggested that the mycelium was appreciably less permeable to the antibiotic in the production phase than during exponential growth. However, a small amount was taken up and much of it was in the soluble fraction of disrupted cells. Bioassays showed that this 14C-labeled antibiotic within the cells had been partially inactivated, suggesting that conversion of streptomycin to an inactive derivative is involved in the mechanism which protects the organism from its metabolite.", "contents": "Rsistance to streptomycin in a producing strain of Streptomyces griseus. Streptomyces griseus S 104 was sensitive to streptomycin during exponential growth in a medium which, in the subsequent stationary phase, supported production of the antibiotic in yields above 200 mug/ml. When antibiotic production began cultures developed a tolerance toward their lethal metabolite. This was not due to an increase in pH associated with antibiotic production, since pH effects on streptomycin sensitivity in S. griseus were in the reverse direction. However, the degree of tolerance was directly related to the amount of cell material present. Streptomycin production caused no change in the proportion of resistant variants in the population, nor did it cause the severe inhibition of protein synthesis observed in non-producing cultures exposed to the antibiotic. The lack of an effect on protein synthesis is attributed to the absence of streptomycin with in the cytoplasm since soluble extracts from mycelium harvested in the production phase were inactive when bioassayed immediately after cell disruption. However, they developed antibacterial activity rapidly when heated, and more slowly when incubated at 25 degrees C. The addition of phosphatase inhibitors during incubation prevented the appearance of antibiotic activity, and it was concluded that a small amount of streptomycin phosphate is present in the mycelium during antibiotic production. Differences in (14C) streptomycin uptake suggested that the mycelium was appreciably less permeable to the antibiotic in the production phase than during exponential growth. However, a small amount was taken up and much of it was in the soluble fraction of disrupted cells. Bioassays showed that this 14C-labeled antibiotic within the cells had been partially inactivated, suggesting that conversion of streptomycin to an inactive derivative is involved in the mechanism which protects the organism from its metabolite."}
{"id": "PMID:235357", "title": "Dual effects of glucose on dicarboxylic acid transport in Kluyveromyces lactis.", "content": "The properties of succinate uptake in succinate-grown Kluyveromyces cells were examined. The rate of succinate transport at 15C exhibits an approximate V-max of 1.2 mumol times h-1 times mg-1 dry weight of cells and an apparent K-m of 18 muM. The uptake process appears to be tightly coupled to metabolism. L-Malate, fumarate, and alpha-ketoglutarate were the only other dicarboxylates tested, which were found to inhibit succinate transport. The aggreement between the order of inhibition of succinate transport by these dicarboxylates and their rates of uptake, as well as the competitive nature of the inhibition are all consistent with the existence of a common carrier system showing specificity for dicarboxylates of the TCA cycle. Cells transferred from succinate to glucose medium rapidly lose their ability to transport succinate. Glucose-grown cells also exhibit an inability to oxidize dicarboxylates or to use them for growth without a very long lag. The dicarboxylate uptake system, therefore, appears to be subject to a strong catabolite repression. The depression of the succinate transport system requires the presence of succinate, as well as low concentrations of glucose.", "contents": "Dual effects of glucose on dicarboxylic acid transport in Kluyveromyces lactis. The properties of succinate uptake in succinate-grown Kluyveromyces cells were examined. The rate of succinate transport at 15C exhibits an approximate V-max of 1.2 mumol times h-1 times mg-1 dry weight of cells and an apparent K-m of 18 muM. The uptake process appears to be tightly coupled to metabolism. L-Malate, fumarate, and alpha-ketoglutarate were the only other dicarboxylates tested, which were found to inhibit succinate transport. The aggreement between the order of inhibition of succinate transport by these dicarboxylates and their rates of uptake, as well as the competitive nature of the inhibition are all consistent with the existence of a common carrier system showing specificity for dicarboxylates of the TCA cycle. Cells transferred from succinate to glucose medium rapidly lose their ability to transport succinate. Glucose-grown cells also exhibit an inability to oxidize dicarboxylates or to use them for growth without a very long lag. The dicarboxylate uptake system, therefore, appears to be subject to a strong catabolite repression. The depression of the succinate transport system requires the presence of succinate, as well as low concentrations of glucose."}
{"id": "PMID:235358", "title": "Bacteriostasis in soils sterilized by gamma irradiation and in reinoculated sterilized soils.", "content": "An agar-disc method was used to compare the bacteriostatic properties of five soils with those of samples of the same soils sterilized by gamma irradiation. For three of the soils, bacteriostasis was removed either partially or entirely by sterilization. Bacteriostasis was completely restored to sterile soil by reinoculating it with natural soil. All the reinoculation treatments restored the level of bacteriostasis equally effectively, whatever the origin of the soil used as inoculum.", "contents": "Bacteriostasis in soils sterilized by gamma irradiation and in reinoculated sterilized soils. An agar-disc method was used to compare the bacteriostatic properties of five soils with those of samples of the same soils sterilized by gamma irradiation. For three of the soils, bacteriostasis was removed either partially or entirely by sterilization. Bacteriostasis was completely restored to sterile soil by reinoculating it with natural soil. All the reinoculation treatments restored the level of bacteriostasis equally effectively, whatever the origin of the soil used as inoculum."}
{"id": "PMID:235359", "title": "Partial purification and properties of a beta-glucosidase from Erwinia herbicola Y46.", "content": "A constitutive beta-glucosidase of Erwinia herbicola Y46 was studied as a prerequisite to an assessment of its significance in the release of bacteriotoxic aglycones from plant beta-glucosides, and the possible effects of the aglycones on the course of such plant diseases as \"fire-blight\". The enzyme was purified 86.5-fold from crude extracts of cells grown on yeast beef broth. Ammonium sulfate precipitation, DEAE-cellulose fractionation, and gel filtration through Sephadex G-100 resulted in a preparation having one peak of activity on isoelectrofocussing, on gel filtration through Sephadex G-200, and on polyacrylamide gel electrophoresis. The latter techniques demonstrated, in addition to the major protein band associated with activity, a single minor impurity. The enzyme was active against p-nitrophenyl-beta-glucoside (p-NPG) and phloridzin, but showed only very slight activity against salicin and arbutin, and no detectable activity against beta-methyl-D-glucoside, cellobiose, lactose, and esculin. The production of beta-glucosidase was maximum at the late log phase of growth on yeast beef broth medium and declined somewhat thereafter. The incorporation of inducers (carbohydrates) in defined basal medium resulted in only small variations in specific activity in the resulting cells; The activity (p-NPG substrate) was not inhibited by D-glucose, phloretin, esculin, salicin, arbutin, lactose, or cellobiose, but was slightly inhibited by 1.0 mM phloridzin. Slight inhibition was observed in the presence of sulfhydryl reagents (iodoacetamide, p-chloromercuribenzoate), but sodium azide, ethylene-diaminetetraacetic acid, Cu2+, and Zn2+ ions produced no effect. The activity was stable, in both crude and purified preparations, over the pH ranges 6.0-7.5 (100% activity) and 4.5-greater than 8.5 (50% activity). The enzyme retained 80% activity after 30 min at 50 degrees C, but only 25% after 30 min at 60 degrees C. The enzyme had a mean K-m value (phloridzin) of 1.35 times 10-4 M, an isoelectric point of 4.75, a molecular weight, determined by Sephadex G-200 gel filtration, of about 122 000, and an optimum pH for activity of 6.5-7.0.", "contents": "Partial purification and properties of a beta-glucosidase from Erwinia herbicola Y46. A constitutive beta-glucosidase of Erwinia herbicola Y46 was studied as a prerequisite to an assessment of its significance in the release of bacteriotoxic aglycones from plant beta-glucosides, and the possible effects of the aglycones on the course of such plant diseases as \"fire-blight\". The enzyme was purified 86.5-fold from crude extracts of cells grown on yeast beef broth. Ammonium sulfate precipitation, DEAE-cellulose fractionation, and gel filtration through Sephadex G-100 resulted in a preparation having one peak of activity on isoelectrofocussing, on gel filtration through Sephadex G-200, and on polyacrylamide gel electrophoresis. The latter techniques demonstrated, in addition to the major protein band associated with activity, a single minor impurity. The enzyme was active against p-nitrophenyl-beta-glucoside (p-NPG) and phloridzin, but showed only very slight activity against salicin and arbutin, and no detectable activity against beta-methyl-D-glucoside, cellobiose, lactose, and esculin. The production of beta-glucosidase was maximum at the late log phase of growth on yeast beef broth medium and declined somewhat thereafter. The incorporation of inducers (carbohydrates) in defined basal medium resulted in only small variations in specific activity in the resulting cells; The activity (p-NPG substrate) was not inhibited by D-glucose, phloretin, esculin, salicin, arbutin, lactose, or cellobiose, but was slightly inhibited by 1.0 mM phloridzin. Slight inhibition was observed in the presence of sulfhydryl reagents (iodoacetamide, p-chloromercuribenzoate), but sodium azide, ethylene-diaminetetraacetic acid, Cu2+, and Zn2+ ions produced no effect. The activity was stable, in both crude and purified preparations, over the pH ranges 6.0-7.5 (100% activity) and 4.5-greater than 8.5 (50% activity). The enzyme retained 80% activity after 30 min at 50 degrees C, but only 25% after 30 min at 60 degrees C. The enzyme had a mean K-m value (phloridzin) of 1.35 times 10-4 M, an isoelectric point of 4.75, a molecular weight, determined by Sephadex G-200 gel filtration, of about 122 000, and an optimum pH for activity of 6.5-7.0."}
{"id": "PMID:235360", "title": "Successful orthotopic free autogenous joint grafts in the dog.", "content": "Thirty free autogenous metacarpal and 26 phalangeal articular cartilages were transplanted in the forefoot of dogs. The graft in each case included the articular surface and a minimal amount of supporting subchondral bone. The majority of the metacarpal grafts retained a normal gross, microscopic, and radioautographic appearance, some for up to 1 year after transplantation. In contradistinction, all of the phalangeal grafts failed, probably because their flatt surface made it impossible to maintain adequate fixation to the host bed. As a result the majority of these grafts became displaced. Analysis of the incorporation of the metacarpal grafts into the host bed showed that this occurred when there was no significant period during which the articular cartilage was without subchondral support. The situation is different in the case of joint grafts with a larger amount of subchondral bone. In these, during the time that this necrotic bone is being resorbed and replaced by normal viable bone, the articular cartilage has extremely limited subchondral support.", "contents": "Successful orthotopic free autogenous joint grafts in the dog. Thirty free autogenous metacarpal and 26 phalangeal articular cartilages were transplanted in the forefoot of dogs. The graft in each case included the articular surface and a minimal amount of supporting subchondral bone. The majority of the metacarpal grafts retained a normal gross, microscopic, and radioautographic appearance, some for up to 1 year after transplantation. In contradistinction, all of the phalangeal grafts failed, probably because their flatt surface made it impossible to maintain adequate fixation to the host bed. As a result the majority of these grafts became displaced. Analysis of the incorporation of the metacarpal grafts into the host bed showed that this occurred when there was no significant period during which the articular cartilage was without subchondral support. The situation is different in the case of joint grafts with a larger amount of subchondral bone. In these, during the time that this necrotic bone is being resorbed and replaced by normal viable bone, the articular cartilage has extremely limited subchondral support."}
{"id": "PMID:235361", "title": "Treatment of acute osteomyelitis in children by closed-tube irrigation: a reassessment.", "content": "The addition of closed-tube irrigation to incision and drainage in the treatment of children with acute osteomyelitis has been found to be associated with: (a) a rate of technical complications of 60%, the most common complications being leaking and plugging of the tube; (b) a 30% rate of superinfection at the site of the wound, the most common organism being Pseudomonas; and (c) an average postoperative hospital stay of 30 days compared with only 16 days for the patients treated by incision and drainage alone. Suction-irrigation in the treatment of acute osteomyelitis in children does not appear to be essential for successful management, and introduces added risks of superinfection and technical complications.", "contents": "Treatment of acute osteomyelitis in children by closed-tube irrigation: a reassessment. The addition of closed-tube irrigation to incision and drainage in the treatment of children with acute osteomyelitis has been found to be associated with: (a) a rate of technical complications of 60%, the most common complications being leaking and plugging of the tube; (b) a 30% rate of superinfection at the site of the wound, the most common organism being Pseudomonas; and (c) an average postoperative hospital stay of 30 days compared with only 16 days for the patients treated by incision and drainage alone. Suction-irrigation in the treatment of acute osteomyelitis in children does not appear to be essential for successful management, and introduces added risks of superinfection and technical complications."}
{"id": "PMID:235362", "title": "Bile aspiration: an experimental study in rabbits.", "content": "It has been shown that bile injected intratracheally in rabbits produces severe pulmonary edema, atelectasis, and focal hemorrhages. The authors investigated the effect of a number of solutions, including physiological concentration of bile, hydrochloric acid pH 1.0, bile salt diluted to 1%, and bile at 100% concentrations. Whenever the bile concentration exceeded 3%, none of the test animals survived. It is not possible to apply directly the results of an experimental animal study to humans. However, the severity of the pulmonary changes produced force the conclusion that bile is a potentially dangerous aspirate in humans.", "contents": "Bile aspiration: an experimental study in rabbits. It has been shown that bile injected intratracheally in rabbits produces severe pulmonary edema, atelectasis, and focal hemorrhages. The authors investigated the effect of a number of solutions, including physiological concentration of bile, hydrochloric acid pH 1.0, bile salt diluted to 1%, and bile at 100% concentrations. Whenever the bile concentration exceeded 3%, none of the test animals survived. It is not possible to apply directly the results of an experimental animal study to humans. However, the severity of the pulmonary changes produced force the conclusion that bile is a potentially dangerous aspirate in humans."}
{"id": "PMID:235363", "title": "Studies on the relationship between the equilibrium curve of oxyhemoglobin and 2,3-diphosphoglycerate in open-heart surgery.", "content": "The relationship between decreased oxygen affinity of hemoglobin and intraerythrocyte 2,3-diphosphoglycerate (2,3 DPG) concentration was confirmed and its existence during the period of open-heart surgery was demonstrated. It is suggested that the trauma sustained by the erythrocytes during their extracorporeal circulation is responsible, in large measure, for the decrease in 2,3 DPG concentration.", "contents": "Studies on the relationship between the equilibrium curve of oxyhemoglobin and 2,3-diphosphoglycerate in open-heart surgery. The relationship between decreased oxygen affinity of hemoglobin and intraerythrocyte 2,3-diphosphoglycerate (2,3 DPG) concentration was confirmed and its existence during the period of open-heart surgery was demonstrated. It is suggested that the trauma sustained by the erythrocytes during their extracorporeal circulation is responsible, in large measure, for the decrease in 2,3 DPG concentration."}
{"id": "PMID:235364", "title": "[Hyperoxemia in extracorporeal circulation].", "content": "The authors demonstrate the effects of hyperoxemia in dogs subjected to extracorporeal circulation. Arterial Po2 was maintained between 100 and 140 mm Hg in a control group and above 200 mm Hg in another group. There was no morbidity or mortality in these experiments. Postoperative functional status as well as hematological and biochemical data were similar in both groups. However, free plasma hemoglobin was 50% higher in animals subjected to hyperoxygenation. It is thus concluded that on the basis of these results hyperoxygenation has no beneficial effect on the animals submitted to total body bypass and moreover that arterial Po2 over 200 mm Hg increases hemolysis.", "contents": "[Hyperoxemia in extracorporeal circulation]. The authors demonstrate the effects of hyperoxemia in dogs subjected to extracorporeal circulation. Arterial Po2 was maintained between 100 and 140 mm Hg in a control group and above 200 mm Hg in another group. There was no morbidity or mortality in these experiments. Postoperative functional status as well as hematological and biochemical data were similar in both groups. However, free plasma hemoglobin was 50% higher in animals subjected to hyperoxygenation. It is thus concluded that on the basis of these results hyperoxygenation has no beneficial effect on the animals submitted to total body bypass and moreover that arterial Po2 over 200 mm Hg increases hemolysis."}
{"id": "PMID:235367", "title": "Properties, inducibility, and an improved method of analysis of aryl hydrocarbon hydroxylase in cultured human lymphocytes.", "content": "The properties and inducibility of aryl hydrocarbon hydroxylase (AHH) in cultured human lymphocytes were studied, and a sensitive method of analysis has been developed. In agreement with other reports, peripheral blood lymphocytes per se had no activity and required pretreatment in culture with a mitogen for conversion to lymphoblasts to possess AHH activity. This activity had an absolute requirement for reduced nicotinamide adenine dinucleotide phosphate. Under our conditions of incubation, reduced nicotinamide adenine dinucleotide (1.3 mM) or ethylenediaminetetraacetic acid disodium salt (1 mM), when added to reduced nicotinamide adenine dinucleotide phosphate-fortified incubation mixture, caused about 30% increase in activity and MnCl2 caused an appreciable inhibition. The reaction was linear with the number of cells, with up to 16.8 X 10-6 cells contained in the incubation mixture, and had a pH optimum of 8.5. The enzyme was fairly stable at -70 degrees and retained about 90% of the original activity for 15 days. The enzyme activity in the mitogen-stimulated lymphocyte cultures appeared slowly and reached a maximum at 48 to 72 hr of incubation at 37 degrees, after which it considerably decayed with time. Viability of the cells in culture also decayed considerably after 72 hr and reached about 50% level at 120 hr. The enzyme was inducible with 3-methylcholanthrene and dibenz(a,h)anthracene. Dibenz(a,h)anthracene was a much more potent inducer than 3-methylcholanthrene and evoked a response in cells that would be considered noninducible with 3-methylcholanthrene. By using purified lymphocytes and Roswell Park Memorial Institute Medium 1640, providing larger surface area during culture, harvesting the cells at the time of minimum cell death and maximum AHH activity, and assaying AHH at its pH optimum of 8.5 instead of 7.6, it was possible to enhance the sensitivity of the assay an average of 17-fold.", "contents": "Properties, inducibility, and an improved method of analysis of aryl hydrocarbon hydroxylase in cultured human lymphocytes. The properties and inducibility of aryl hydrocarbon hydroxylase (AHH) in cultured human lymphocytes were studied, and a sensitive method of analysis has been developed. In agreement with other reports, peripheral blood lymphocytes per se had no activity and required pretreatment in culture with a mitogen for conversion to lymphoblasts to possess AHH activity. This activity had an absolute requirement for reduced nicotinamide adenine dinucleotide phosphate. Under our conditions of incubation, reduced nicotinamide adenine dinucleotide (1.3 mM) or ethylenediaminetetraacetic acid disodium salt (1 mM), when added to reduced nicotinamide adenine dinucleotide phosphate-fortified incubation mixture, caused about 30% increase in activity and MnCl2 caused an appreciable inhibition. The reaction was linear with the number of cells, with up to 16.8 X 10-6 cells contained in the incubation mixture, and had a pH optimum of 8.5. The enzyme was fairly stable at -70 degrees and retained about 90% of the original activity for 15 days. The enzyme activity in the mitogen-stimulated lymphocyte cultures appeared slowly and reached a maximum at 48 to 72 hr of incubation at 37 degrees, after which it considerably decayed with time. Viability of the cells in culture also decayed considerably after 72 hr and reached about 50% level at 120 hr. The enzyme was inducible with 3-methylcholanthrene and dibenz(a,h)anthracene. Dibenz(a,h)anthracene was a much more potent inducer than 3-methylcholanthrene and evoked a response in cells that would be considered noninducible with 3-methylcholanthrene. By using purified lymphocytes and Roswell Park Memorial Institute Medium 1640, providing larger surface area during culture, harvesting the cells at the time of minimum cell death and maximum AHH activity, and assaying AHH at its pH optimum of 8.5 instead of 7.6, it was possible to enhance the sensitivity of the assay an average of 17-fold."}
{"id": "PMID:235368", "title": "Separation of myocardial cytoplasmic acidic inhibitor proteins which inhibit hepatic protein biosynthesis in vitro.", "content": "Cytoplasmic inhibitor proteins of rabbit and pig myocardium have been separated and their in-vitro effects on hepatic cell-free protein biosynthesis reported. Three protein peaks could be separated from myocardial cytoplasmic pH 5 fraction by DEAE and CM cellulose column chromatography. There was a difference in the elution pattern of the acidic inhibitor proteins obtained from pig and rabbit myocardium. The myocardial acidic inhibitor proteins inhibited a liver cell-free protein biosynthesizing system, but not a myocardial cell-free system.", "contents": "Separation of myocardial cytoplasmic acidic inhibitor proteins which inhibit hepatic protein biosynthesis in vitro. Cytoplasmic inhibitor proteins of rabbit and pig myocardium have been separated and their in-vitro effects on hepatic cell-free protein biosynthesis reported. Three protein peaks could be separated from myocardial cytoplasmic pH 5 fraction by DEAE and CM cellulose column chromatography. There was a difference in the elution pattern of the acidic inhibitor proteins obtained from pig and rabbit myocardium. The myocardial acidic inhibitor proteins inhibited a liver cell-free protein biosynthesizing system, but not a myocardial cell-free system."}
{"id": "PMID:235369", "title": "Effects of bretylium and lidocaine on ventricular fibrillation in the isolated rabbit heart.", "content": "We studied the effects of bretylium tosylate and lidocaine on ventricular fibrillation in the isolated, perfused rabbit heart induced by perfusion with potassium-deficient solutions and by premature stimuli. The purpose of the study was to determine if the reported antifibrillatory effects of the drugs could be reproduced in the absence of an intact sympathetic nervous system. Lidocaine in the concentration of 5 mug/ml. prevented ventricular fibrillation induced by both methods while bretylium, in concentrations of 25 to 50 mug/ml. prevented neither type of filbrillation. These results indicate that the antifibrillatory effects of lidocaine can be attributed to drug-induced alterations in cellular electrophysiology, whereas those of bretylium are independent of such changes. Our study suggests that the reported antifibrillatory capability of bretylium is related to the drug's effects at sympathetic nerve terminals and thus is dependent upon an intact sympathetic nervous system.", "contents": "Effects of bretylium and lidocaine on ventricular fibrillation in the isolated rabbit heart. We studied the effects of bretylium tosylate and lidocaine on ventricular fibrillation in the isolated, perfused rabbit heart induced by perfusion with potassium-deficient solutions and by premature stimuli. The purpose of the study was to determine if the reported antifibrillatory effects of the drugs could be reproduced in the absence of an intact sympathetic nervous system. Lidocaine in the concentration of 5 mug/ml. prevented ventricular fibrillation induced by both methods while bretylium, in concentrations of 25 to 50 mug/ml. prevented neither type of filbrillation. These results indicate that the antifibrillatory effects of lidocaine can be attributed to drug-induced alterations in cellular electrophysiology, whereas those of bretylium are independent of such changes. Our study suggests that the reported antifibrillatory capability of bretylium is related to the drug's effects at sympathetic nerve terminals and thus is dependent upon an intact sympathetic nervous system."}
{"id": "PMID:235370", "title": "Spermatogenesis in Anthozoa: differentiation of the spermatid.", "content": "The fine structure of spermatids has been examined in Calliactis, Protanthea, Gonactinia and Parazoanthus (Cnidaria, Anthozoa). The sperm cells are relatively simple and lack distinct acrosomes. Their nuclei, spherical in the zoanthid, in the actinians are slendertipped cones. Condensation of the chromatin is interpreted in terms of progressive coiling of densely-stained filaments and the elimination of nucleoplasm. Nuclear elongation occurs in the absence of microtubules. A well-developed centriolar complex is attached to the nuclear envelope by fibres and in this area (that of a shallow fossa in actinian spern) the nuclear membranes seem to be thickened. The centrioles are surrounded by a mitochondrial collar, especially pronounced in Calliactis. In contact with the mitochondria and nucleus is a ring of lipid-containing vesicles 300-700 nm in diameter. A system of densely-staining vesicles 150-300 nm in size corresponds to the \"pro-acrosomal vesicles\" described for other coelenterates. They are scattered in the peripheral cytoplasm and are regarded as derivatives of the endoplasmic reticulum. Problems of organelle function and of differentiation during spermiogenesis are discussed.", "contents": "Spermatogenesis in Anthozoa: differentiation of the spermatid. The fine structure of spermatids has been examined in Calliactis, Protanthea, Gonactinia and Parazoanthus (Cnidaria, Anthozoa). The sperm cells are relatively simple and lack distinct acrosomes. Their nuclei, spherical in the zoanthid, in the actinians are slendertipped cones. Condensation of the chromatin is interpreted in terms of progressive coiling of densely-stained filaments and the elimination of nucleoplasm. Nuclear elongation occurs in the absence of microtubules. A well-developed centriolar complex is attached to the nuclear envelope by fibres and in this area (that of a shallow fossa in actinian spern) the nuclear membranes seem to be thickened. The centrioles are surrounded by a mitochondrial collar, especially pronounced in Calliactis. In contact with the mitochondria and nucleus is a ring of lipid-containing vesicles 300-700 nm in diameter. A system of densely-staining vesicles 150-300 nm in size corresponds to the \"pro-acrosomal vesicles\" described for other coelenterates. They are scattered in the peripheral cytoplasm and are regarded as derivatives of the endoplasmic reticulum. Problems of organelle function and of differentiation during spermiogenesis are discussed."}
{"id": "PMID:235372", "title": "Some physico-chemical properties of aqueous solutions of N alpha-acyl-l-histidine.", "content": "The critical micelle concentrations of aqueous solutions of N alpha-acyl-L-histidine have been determined by the spectral shift method with Rhodamine 6G and by the light scattering method. With the spectral shift method critical micelle concentrations of 40, 9.0, 1.0, 0.11, and 0.012 mM were obtained for N alpha-acyl-L-histidine containing saturated acids of 8, 10, 12, 14, and 16 carbons respectively, at 45 degrees C and pH 8.6 in the absence of added salt. For the homologs containing 10, 12, and 14 carbon acids, critical micelle concentration of 9.0, 1.0 and 0.11 mM were determined by the light scattering method. The light scattering studies yield micelle weights of 60, 66, and 84 thousand for the C-10, C-12, and C-14 homologs, respectively. N alpha-acyl-L-histidine is an unusual surfactant in that the hydrophilic portion of the molecule is relatively large and contains both an ionic group (carboxylate group) and a nonionic group (imidazole side-chain). The bulky hydrophilic group of N alpha-acyl-L-histidine causes this molecule to exhibit physico-chemical behavior which is not typical of that exhibited by most ionic surfactants. In particular, the dependence of the critical micelle concentration on the acyl chain length and on the concentration of added salt is atypical. Chemical shift measurements (by NMR) on the C-2 and C-5 protons of imidazole in micellar N alpha-dodecanoyl-L-histidine indicate that the imidazole group is, indeed, positioned at the water-micelle interface.", "contents": "Some physico-chemical properties of aqueous solutions of N alpha-acyl-l-histidine. The critical micelle concentrations of aqueous solutions of N alpha-acyl-L-histidine have been determined by the spectral shift method with Rhodamine 6G and by the light scattering method. With the spectral shift method critical micelle concentrations of 40, 9.0, 1.0, 0.11, and 0.012 mM were obtained for N alpha-acyl-L-histidine containing saturated acids of 8, 10, 12, 14, and 16 carbons respectively, at 45 degrees C and pH 8.6 in the absence of added salt. For the homologs containing 10, 12, and 14 carbon acids, critical micelle concentration of 9.0, 1.0 and 0.11 mM were determined by the light scattering method. The light scattering studies yield micelle weights of 60, 66, and 84 thousand for the C-10, C-12, and C-14 homologs, respectively. N alpha-acyl-L-histidine is an unusual surfactant in that the hydrophilic portion of the molecule is relatively large and contains both an ionic group (carboxylate group) and a nonionic group (imidazole side-chain). The bulky hydrophilic group of N alpha-acyl-L-histidine causes this molecule to exhibit physico-chemical behavior which is not typical of that exhibited by most ionic surfactants. In particular, the dependence of the critical micelle concentration on the acyl chain length and on the concentration of added salt is atypical. Chemical shift measurements (by NMR) on the C-2 and C-5 protons of imidazole in micellar N alpha-dodecanoyl-L-histidine indicate that the imidazole group is, indeed, positioned at the water-micelle interface."}
{"id": "PMID:235373", "title": "Studies on phosphatidylcholine model membranes. I. Iodine permeability measurement by specific ion electrode.", "content": "An iodide specific ion electrode was used to measure iodide released from egg phosphatidylcholine liposomes after passage through an ion exchange column. The permeation process was shown to be a sum of two separate first order processes. The method permits linear initial rates of iodide release to be determined for the first 5 min of permeation. Iodide permeability in the absence of Tris buffer was found to be a decreasing function of pH. In the presence of Tris, iodide permeability went through a minimum ofrom ph 7.3-8.5. the permeability was found to decrease when cholesterol was incorporated into the liposomes.", "contents": "Studies on phosphatidylcholine model membranes. I. Iodine permeability measurement by specific ion electrode. An iodide specific ion electrode was used to measure iodide released from egg phosphatidylcholine liposomes after passage through an ion exchange column. The permeation process was shown to be a sum of two separate first order processes. The method permits linear initial rates of iodide release to be determined for the first 5 min of permeation. Iodide permeability in the absence of Tris buffer was found to be a decreasing function of pH. In the presence of Tris, iodide permeability went through a minimum ofrom ph 7.3-8.5. the permeability was found to decrease when cholesterol was incorporated into the liposomes."}
{"id": "PMID:235374", "title": "Modulation by prostaglandins of adrenergic transmission in the isolated perfused rabbit and rat kidney.", "content": "In the isolated perfused rabbit kidney prostaglandins (PGS) E1 (0.02-0-1 ng/ml), E2 (0.02-0.1 ng/ml), and A2 (1-5 ng/ml) inhibited the vasoconstrictor responses to sympathetic nerve stimulation by 21-44%, 31-39%, and 20-23%, respectively, without alerting those to injected norepinephrine. In contrast, in the rat kidney PGE1 (0.5 ng/ml), PGE2 (0.5 ng/ml), and PGA2 (5 ng/ml) enhanced the vasoconstrictor responses to sympathetic nerve stimulation by 41%, 27%, and 11%, respectively; the equiconstrictor responses to injected norepinephrine remained unaltered. Higher concentrations of these agents produced vasodilation in the rabbit kidney and vasoconstriction in the rat kidney. In both species PGF2alpha produced vasoconstriction and enhanced the response to both adrenergic stumuli. In the rabbit kidney inhibitors of PG synthesis augmented the responses to sympathetic nerve stimulation without altering those to injected norepinephrine, whereas in the rat kidney inhibition of the responses to both adrenergic stimuli occurred. Arachidonic acid inhibited the vasoconstrictor responses to sympathetic nerve stimulation in the rabbit kidney, but in the rat kidney it caused augmentation of these responses. Since these effects of arachidonic acid were reduced by indomethacin, they appear to be mediated through the acid's conversion to PGS. We conclude that PGS of the E series modulate adrenergic transmission in the kidney and that their modulatory actions are species dependent.", "contents": "Modulation by prostaglandins of adrenergic transmission in the isolated perfused rabbit and rat kidney. In the isolated perfused rabbit kidney prostaglandins (PGS) E1 (0.02-0-1 ng/ml), E2 (0.02-0.1 ng/ml), and A2 (1-5 ng/ml) inhibited the vasoconstrictor responses to sympathetic nerve stimulation by 21-44%, 31-39%, and 20-23%, respectively, without alerting those to injected norepinephrine. In contrast, in the rat kidney PGE1 (0.5 ng/ml), PGE2 (0.5 ng/ml), and PGA2 (5 ng/ml) enhanced the vasoconstrictor responses to sympathetic nerve stimulation by 41%, 27%, and 11%, respectively; the equiconstrictor responses to injected norepinephrine remained unaltered. Higher concentrations of these agents produced vasodilation in the rabbit kidney and vasoconstriction in the rat kidney. In both species PGF2alpha produced vasoconstriction and enhanced the response to both adrenergic stumuli. In the rabbit kidney inhibitors of PG synthesis augmented the responses to sympathetic nerve stimulation without altering those to injected norepinephrine, whereas in the rat kidney inhibition of the responses to both adrenergic stimuli occurred. Arachidonic acid inhibited the vasoconstrictor responses to sympathetic nerve stimulation in the rabbit kidney, but in the rat kidney it caused augmentation of these responses. Since these effects of arachidonic acid were reduced by indomethacin, they appear to be mediated through the acid's conversion to PGS. We conclude that PGS of the E series modulate adrenergic transmission in the kidney and that their modulatory actions are species dependent."}
{"id": "PMID:235375", "title": "Cardiac performance and mortality early after intracardiac surgery in infants and young children.", "content": "One hundred thirty-nine infants and small children less than 48 months old were studied during the first 72 hours after intracardiac surgery for a variety of lesions. The hospital mortality rate was 19.4% (27 patients); 16 of those dying succumbed from acute cardiac failure. Deaths from acute cardiac failure were commonest in patients with low cardiac index (CI), and a continuous probability curve relates the two. The mean CI for all patients was 2.51 plus or minus 0.794 l-min minus 1-m minus 2, and that for individual patients varied between 0.6 and 4.9. Cardiac output normalized by surface area (cardiac index) correlated weakly with age. cardiac output normalized by weight did not correlate with age; Mean mixed venous oxygen partial pressure (P-vO2)varied between 17 and 60 mm Hg, and the weighted mean for the group of 80 patients in whom it was obtained was 33.1 plus or minus 6.57 mm Hg. CI and P-vO2 were only slightly related. Acute cardiac deaths occurred more frequently in patients with low P-vO2. Acute cardiac death was more reliably predicted using CI and P-vO2 together than either alone. The average of the mean arterial pressure was 80.5 plus or minus 2.53 mm Hg, and this did not correlate with CI. Mean average systemic vascular resistance was 30.0 plus or minus 8.395 SRU. We conclude that in such patients treatment should be directed toward keeping CI greater than 2.0 l-min minus 1-m minus 2 and P-vO2 greater than 30 mm Hg; that the possibility of maintaining adequate CI and P-vO2 is not related to the age of the patient but is related to the malformation treated; and that a therapeutic trial of reducing left ventricular afterload is indicated in some of these patients.", "contents": "Cardiac performance and mortality early after intracardiac surgery in infants and young children. One hundred thirty-nine infants and small children less than 48 months old were studied during the first 72 hours after intracardiac surgery for a variety of lesions. The hospital mortality rate was 19.4% (27 patients); 16 of those dying succumbed from acute cardiac failure. Deaths from acute cardiac failure were commonest in patients with low cardiac index (CI), and a continuous probability curve relates the two. The mean CI for all patients was 2.51 plus or minus 0.794 l-min minus 1-m minus 2, and that for individual patients varied between 0.6 and 4.9. Cardiac output normalized by surface area (cardiac index) correlated weakly with age. cardiac output normalized by weight did not correlate with age; Mean mixed venous oxygen partial pressure (P-vO2)varied between 17 and 60 mm Hg, and the weighted mean for the group of 80 patients in whom it was obtained was 33.1 plus or minus 6.57 mm Hg. CI and P-vO2 were only slightly related. Acute cardiac deaths occurred more frequently in patients with low P-vO2. Acute cardiac death was more reliably predicted using CI and P-vO2 together than either alone. The average of the mean arterial pressure was 80.5 plus or minus 2.53 mm Hg, and this did not correlate with CI. Mean average systemic vascular resistance was 30.0 plus or minus 8.395 SRU. We conclude that in such patients treatment should be directed toward keeping CI greater than 2.0 l-min minus 1-m minus 2 and P-vO2 greater than 30 mm Hg; that the possibility of maintaining adequate CI and P-vO2 is not related to the age of the patient but is related to the malformation treated; and that a therapeutic trial of reducing left ventricular afterload is indicated in some of these patients."}
{"id": "PMID:235377", "title": "Use of carbon dioxide- and oxygen-tonometered phosphate-bicarbonate-chloride-glycerol-water mixtures for calibration and control of pH, pCO2, and pO2 electrode systems.", "content": "Calibration of pH, PCO2, and PO2 electrode systems of modern blood-gas analyzers, designed with one sample cuvet for measurement, is mostly performed separately with buffer solutions of known pH, PCO2, and PO2 for doing such calibrations simultaneously, containing phosphate, bicarbonate, and chloride in glycerol-water mixtures as solvent. A method is suggested for computing the relation between pH and log PCO2 of these solutions in equilibrium with carbon dioxide gas. It is demonstrated that a solution of phosphate (Na2HPO4, KH2PO4, each 25 mmol/liter), bicarbonate (NaHCO3, 30 mmol/liter), and chloride (Nacl, 30 mmol/liter) in glycerol-water mixture (3/7 by vol) and equilibrated with CO2 in air (4 vol/100 vol) and CO2 in  nitrogen (8 vol/100 vol), respectively, makes possible acurate and simultaneous calibration of the pH, PCO2, PO2 electrodes of a Corning Model 165 blood-gas analyzer. Similar solutions may also be used for quality-control of blood-gas measurement.", "contents": "Use of carbon dioxide- and oxygen-tonometered phosphate-bicarbonate-chloride-glycerol-water mixtures for calibration and control of pH, pCO2, and pO2 electrode systems. Calibration of pH, PCO2, and PO2 electrode systems of modern blood-gas analyzers, designed with one sample cuvet for measurement, is mostly performed separately with buffer solutions of known pH, PCO2, and PO2 for doing such calibrations simultaneously, containing phosphate, bicarbonate, and chloride in glycerol-water mixtures as solvent. A method is suggested for computing the relation between pH and log PCO2 of these solutions in equilibrium with carbon dioxide gas. It is demonstrated that a solution of phosphate (Na2HPO4, KH2PO4, each 25 mmol/liter), bicarbonate (NaHCO3, 30 mmol/liter), and chloride (Nacl, 30 mmol/liter) in glycerol-water mixture (3/7 by vol) and equilibrated with CO2 in air (4 vol/100 vol) and CO2 in  nitrogen (8 vol/100 vol), respectively, makes possible acurate and simultaneous calibration of the pH, PCO2, PO2 electrodes of a Corning Model 165 blood-gas analyzer. Similar solutions may also be used for quality-control of blood-gas measurement."}
{"id": "PMID:235378", "title": "New, simple maltogenic assay for mechanized determination of alpha-amylase activity in serum and urine.", "content": "We report a new method for the mechanized determination of serum and urinary alpha-amylase by use of a continuous-flow system, based on the measurement of maltose formed by incubating the sample with amylodextrin at pH 7 and 40 degrees C. After dialysis, maltose is converted enzymatically to glucose, which is measured by Trinder's glucose oxidase-peroxidase method [J. Clin. Pathol. 22, 246 (1969)]. The reaction is linear for amylase activities up to 1400 Somogyi units/dl (2560 U/liter) and for maltose concentrations through 1500 mg/dl. No blank assay is required; consequently precision is improved and the automated system is simplified. Calibration with primary maltose standards increases accuracy and reliability. Common reducing substances in serum and urine do not interfere at their normal concentrations. There is a linear correlation between the results of this method and those of chromogenic and iodometric methods for normal and pathologic sera and urines. The chromogenic method yields significantly higher results and the iodometric method significantly lower results than this maltogenic method for elevated amylase activities. The normal range is 40-140 Somogyi units/dl (73-256 U/liter).", "contents": "New, simple maltogenic assay for mechanized determination of alpha-amylase activity in serum and urine. We report a new method for the mechanized determination of serum and urinary alpha-amylase by use of a continuous-flow system, based on the measurement of maltose formed by incubating the sample with amylodextrin at pH 7 and 40 degrees C. After dialysis, maltose is converted enzymatically to glucose, which is measured by Trinder's glucose oxidase-peroxidase method [J. Clin. Pathol. 22, 246 (1969)]. The reaction is linear for amylase activities up to 1400 Somogyi units/dl (2560 U/liter) and for maltose concentrations through 1500 mg/dl. No blank assay is required; consequently precision is improved and the automated system is simplified. Calibration with primary maltose standards increases accuracy and reliability. Common reducing substances in serum and urine do not interfere at their normal concentrations. There is a linear correlation between the results of this method and those of chromogenic and iodometric methods for normal and pathologic sera and urines. The chromogenic method yields significantly higher results and the iodometric method significantly lower results than this maltogenic method for elevated amylase activities. The normal range is 40-140 Somogyi units/dl (73-256 U/liter)."}
{"id": "PMID:235379", "title": "Fluorometric assay of serum gamma-glutamyltransferase in solution and on a semi-solid surface.", "content": "We describe an enzymatic, fluorometric method for measuring the activity of serum gamma-glutamyltransferase (EC 2.3.2.2) in solution and on silicone rubber pads. N-gamma-L-Glutamyl-alpha-naphthylamide in tris(hydroxymethyl)aminomethane buffer is used as substrate. In solution, measurements are performed at 37 degrees C with use of a reaction volume of 3.0 ml, in Pyrex cuvets. Measurements on silicone rubber pads are also made at 37 degrees C, after establishing a stable substrate film by lyophilizing the reagent for the gamma-glutamyltransferase assay on the surface of the pads. Only 10-50 mul of buffered substrate and serum containing the enzyme to make a total volume of 60 mul are necessary for each assay. The rate of appearance of alpha-naphthylamine fluorescence (lambda ex equals 344 nm; lambda em equals 445 nm), liberated from N-gamma-L-glutamyl-alpha-naphthylamide by the enzymatic action of gamma-glutamyl-transferase, is measured and equated to its activity in serum. Calibration plots of the change in fluorescence per min vs. enzyme concentration for measurements in solution and on pads show a good proportionality in the range of 26.5-265 U/liter, and indicate the usefulness of these methods.", "contents": "Fluorometric assay of serum gamma-glutamyltransferase in solution and on a semi-solid surface. We describe an enzymatic, fluorometric method for measuring the activity of serum gamma-glutamyltransferase (EC 2.3.2.2) in solution and on silicone rubber pads. N-gamma-L-Glutamyl-alpha-naphthylamide in tris(hydroxymethyl)aminomethane buffer is used as substrate. In solution, measurements are performed at 37 degrees C with use of a reaction volume of 3.0 ml, in Pyrex cuvets. Measurements on silicone rubber pads are also made at 37 degrees C, after establishing a stable substrate film by lyophilizing the reagent for the gamma-glutamyltransferase assay on the surface of the pads. Only 10-50 mul of buffered substrate and serum containing the enzyme to make a total volume of 60 mul are necessary for each assay. The rate of appearance of alpha-naphthylamine fluorescence (lambda ex equals 344 nm; lambda em equals 445 nm), liberated from N-gamma-L-glutamyl-alpha-naphthylamide by the enzymatic action of gamma-glutamyl-transferase, is measured and equated to its activity in serum. Calibration plots of the change in fluorescence per min vs. enzyme concentration for measurements in solution and on pads show a good proportionality in the range of 26.5-265 U/liter, and indicate the usefulness of these methods."}
{"id": "PMID:235380", "title": "A more sensitive automated method for determination of ornithine carbamoyltransferase activity in human serum.", "content": "Ornithine carbamoyltransferase (EC 2.1.3.3) activity is a sensitive, specific indicator of hepatocellular injury. This paper describes development of an improved automated procedure for measurement of this activity. Triethanolamine-ethylenediaminetetraacetate is used as a buffer, and activity is determined by measuring the concentration of the product, citrulline. Kinetic studies have been performed to determine optimal pH and L-ornithine and carbamoyl phosphate concentrations. Recovery of citrulline was studied. The upper limit of normal obtained in a study of 106 blood-bank donors was 6 U/liter. The automated procedure developed as a result of these studies, in which optimal assay conditions are used, produces a threefold increase in sensitivity and permits use of a sample volume of 1 ml.", "contents": "A more sensitive automated method for determination of ornithine carbamoyltransferase activity in human serum. Ornithine carbamoyltransferase (EC 2.1.3.3) activity is a sensitive, specific indicator of hepatocellular injury. This paper describes development of an improved automated procedure for measurement of this activity. Triethanolamine-ethylenediaminetetraacetate is used as a buffer, and activity is determined by measuring the concentration of the product, citrulline. Kinetic studies have been performed to determine optimal pH and L-ornithine and carbamoyl phosphate concentrations. Recovery of citrulline was studied. The upper limit of normal obtained in a study of 106 blood-bank donors was 6 U/liter. The automated procedure developed as a result of these studies, in which optimal assay conditions are used, produces a threefold increase in sensitivity and permits use of a sample volume of 1 ml."}
{"id": "PMID:235382", "title": "A new colorimetric method for the determination of NADH/NADPH dependent  glutathione reductase in erythrocytes and in plasma.", "content": "A simple and rapid colorimetric method for the assay of erythrocyte and plasma glutathione reductase (GR) activity is described. The method is based on the colorimetric measurement of reduced glutathione (GSH) (1) produced when the enzyme is incubated with oxidised glutathione (GSSG) in the presence of either reduced nicotinamide adenine dinucleotide (NADH) or reduced nicotinamide adenine dinucleotide phosphate (NADPH). Results of investigations on the effects of substrate and coenzyme concentrations, pH, EDTA, sodium/potassium chloride, and time, on enzyme activity are presented. Erythrocyte and plasma NADH-GR and NADPH-GR activities in 100 healthy blood donors, and 85 cord blood samples and plasma NADH-GR and NADPH-GR levels in patients with various disease conditions are given.", "contents": "A new colorimetric method for the determination of NADH/NADPH dependent  glutathione reductase in erythrocytes and in plasma. A simple and rapid colorimetric method for the assay of erythrocyte and plasma glutathione reductase (GR) activity is described. The method is based on the colorimetric measurement of reduced glutathione (GSH) (1) produced when the enzyme is incubated with oxidised glutathione (GSSG) in the presence of either reduced nicotinamide adenine dinucleotide (NADH) or reduced nicotinamide adenine dinucleotide phosphate (NADPH). Results of investigations on the effects of substrate and coenzyme concentrations, pH, EDTA, sodium/potassium chloride, and time, on enzyme activity are presented. Erythrocyte and plasma NADH-GR and NADPH-GR activities in 100 healthy blood donors, and 85 cord blood samples and plasma NADH-GR and NADPH-GR levels in patients with various disease conditions are given."}
{"id": "PMID:235384", "title": "Microassay of human erythrocyte catechol-O-methyltransferase: removal of inhibitory calcium ion with chelating resin.", "content": "A radiochemical micromethod for the determination of catechol-O-methyltransferase (COMT) activity in human red blood cells (RBC) is described. The method avoids artifacts that occur with other assay procedures. Erythrocyte lysates are exposed to a particulate chelating agent (Chelex-100) to remove endogenous divalent cations that inhibit COMT. 3,4-Dihydroxybenzoic acid rather than norepinephrine is used as a substrate to increase both the sensitivity and the reproducibility of the procedure. An internal standard of purified rat liver COMT is added to lysates to detect possible variations in endogenous activators or inhibitors of the enzyme. Blood samples from 373 unselected subjects age 16-18 were assayed for RBC COMT activity with this assay procedure. The COMT activity in these blood samples ranged from 3-25 units with a mean activity of 11.3 plus or minus 4.2 (mean plus or minus S.D.).", "contents": "Microassay of human erythrocyte catechol-O-methyltransferase: removal of inhibitory calcium ion with chelating resin. A radiochemical micromethod for the determination of catechol-O-methyltransferase (COMT) activity in human red blood cells (RBC) is described. The method avoids artifacts that occur with other assay procedures. Erythrocyte lysates are exposed to a particulate chelating agent (Chelex-100) to remove endogenous divalent cations that inhibit COMT. 3,4-Dihydroxybenzoic acid rather than norepinephrine is used as a substrate to increase both the sensitivity and the reproducibility of the procedure. An internal standard of purified rat liver COMT is added to lysates to detect possible variations in endogenous activators or inhibitors of the enzyme. Blood samples from 373 unselected subjects age 16-18 were assayed for RBC COMT activity with this assay procedure. The COMT activity in these blood samples ranged from 3-25 units with a mean activity of 11.3 plus or minus 4.2 (mean plus or minus S.D.)."}
{"id": "PMID:235385", "title": "A method for the determination of sphingomyelinase activity.", "content": "A method is presented for the determination of the activity of sphingomyelinase. It is based on the determination of sphingomyelin before and after enzymatic conversion with the aid of a quantitative paper chromatographic analysis of phospholipids. This method is used for the determination of sphingomyelinase activity in various tissues such as those of the human brain and liver and fibroblast cultures. Normal values are presented.", "contents": "A method for the determination of sphingomyelinase activity. A method is presented for the determination of the activity of sphingomyelinase. It is based on the determination of sphingomyelin before and after enzymatic conversion with the aid of a quantitative paper chromatographic analysis of phospholipids. This method is used for the determination of sphingomyelinase activity in various tissues such as those of the human brain and liver and fibroblast cultures. Normal values are presented."}
{"id": "PMID:235386", "title": "Mannosidosis: deficiency of a specific alpha-mannosidase component in cultured fibroblasts.", "content": "Evidence is prisented which shows that the enzymatic defect in mannosidosis, the deficiency of alpha-mannosidase, is expressed in cultured skin fibroblasts from patients with mannosidosis. Additionally, by Cellogel electrophoresis, the enzyme can be separated into two major components (a heat stable component missing in mannosidosis fibroblasts with a pH optimum of 3.6-4.0 and a heat labile component present in mannosidosis fibroblasts with a pH optimum of 5.6-6.0). The specific activity and electrophoresis of alpha-mannosidase from cultured amniotic fluid cells are also shown to be similar to cultured skin fibroblasts.", "contents": "Mannosidosis: deficiency of a specific alpha-mannosidase component in cultured fibroblasts. Evidence is prisented which shows that the enzymatic defect in mannosidosis, the deficiency of alpha-mannosidase, is expressed in cultured skin fibroblasts from patients with mannosidosis. Additionally, by Cellogel electrophoresis, the enzyme can be separated into two major components (a heat stable component missing in mannosidosis fibroblasts with a pH optimum of 3.6-4.0 and a heat labile component present in mannosidosis fibroblasts with a pH optimum of 5.6-6.0). The specific activity and electrophoresis of alpha-mannosidase from cultured amniotic fluid cells are also shown to be similar to cultured skin fibroblasts."}
{"id": "PMID:235387", "title": "A new, highly sensitive and specific assay for chymotrypsin.", "content": "1. A simple, highly sensitive, specific fluorometric method for the determination of chymotrypsin is described. 2. The new substrate utilized in this assay, N-glutaryl-glycyl-glycyl-l-phenylalanine beta-naphthylamide (GGPNA), is readily soluble in water, stable and highly specific for chymotrypsin. It is not degraded by a large excess of carboxypeptidase B, elastase, thrombin or plasmin and is virtually resistant to trypsin. 3. GGPNA is extremely sensitive to the action of chymotrypsin and permits detection of enzyme concentrations as low as 1 ng/ml. Linearity between enzyme concentration and fluorescence produced is maintained up to at least 3000 ng/ml. 4. alpha2-Macroglobulin-bound chymotrypsin hydrolyzes GGPNA at a rate about 2/3 of that exhibited by the free enzyme. 5. Bile pigments in amounts normally found in duodenal juice or traces of blood do not interfere with the assay. 6. GG PNA which releases beta-naphthylamine upon hydrolysis is suitable also for colorimetric and histological determination of chymotrypsin.", "contents": "A new, highly sensitive and specific assay for chymotrypsin. 1. A simple, highly sensitive, specific fluorometric method for the determination of chymotrypsin is described. 2. The new substrate utilized in this assay, N-glutaryl-glycyl-glycyl-l-phenylalanine beta-naphthylamide (GGPNA), is readily soluble in water, stable and highly specific for chymotrypsin. It is not degraded by a large excess of carboxypeptidase B, elastase, thrombin or plasmin and is virtually resistant to trypsin. 3. GGPNA is extremely sensitive to the action of chymotrypsin and permits detection of enzyme concentrations as low as 1 ng/ml. Linearity between enzyme concentration and fluorescence produced is maintained up to at least 3000 ng/ml. 4. alpha2-Macroglobulin-bound chymotrypsin hydrolyzes GGPNA at a rate about 2/3 of that exhibited by the free enzyme. 5. Bile pigments in amounts normally found in duodenal juice or traces of blood do not interfere with the assay. 6. GG PNA which releases beta-naphthylamine upon hydrolysis is suitable also for colorimetric and histological determination of chymotrypsin."}
{"id": "PMID:235389", "title": "Gd(minus)Matam, an African glucose-6-phosphate dehydrogenase variant with enzyme deficiency. Biochemical and immunological properties in various hemopoietic tissues.", "content": "Two unrelated Senegalese patients, both native of the Matam province, were found to have the same deficient G6PD variant. One has no hematological history, the other had several induced acute hemolytic episodes. The deficiency was almost complete in red blood cells and 20-30 percent of the normal level in leukocytes and platelets; in leukocytes the deficiency was due to a decrease in the molecular specific activity of the enzyme to which a molecular instability was added, explaining the greater deficiency in red blood cells. The electrophoretic mobility was slightly fast in leukocytes and platelets but normal in red blood cells. This pattern was confirmed by electrofocusing in ampholine-acrylamide gel. From a kinetic point of view, these enzymes were characterized by a lowered Km (G6P) (13 to 20 muM) a normal Km (NADP+), a Ki (NADPH) increased about twice, a thermal instability, a biphasic pH curve and an increased activation energy (15 kcal/mole). The polymorphonuclear cells were functionally strictly normal: engulfment, nitroblue tetrazolium (NBT) reduction test, induced iodination, and oxygen consumption were normal. The authors discuss the importance of post-synthetic modifications of the muted enzymes and their repercussions on the enzyme characteristics.", "contents": "Gd(minus)Matam, an African glucose-6-phosphate dehydrogenase variant with enzyme deficiency. Biochemical and immunological properties in various hemopoietic tissues. Two unrelated Senegalese patients, both native of the Matam province, were found to have the same deficient G6PD variant. One has no hematological history, the other had several induced acute hemolytic episodes. The deficiency was almost complete in red blood cells and 20-30 percent of the normal level in leukocytes and platelets; in leukocytes the deficiency was due to a decrease in the molecular specific activity of the enzyme to which a molecular instability was added, explaining the greater deficiency in red blood cells. The electrophoretic mobility was slightly fast in leukocytes and platelets but normal in red blood cells. This pattern was confirmed by electrofocusing in ampholine-acrylamide gel. From a kinetic point of view, these enzymes were characterized by a lowered Km (G6P) (13 to 20 muM) a normal Km (NADP+), a Ki (NADPH) increased about twice, a thermal instability, a biphasic pH curve and an increased activation energy (15 kcal/mole). The polymorphonuclear cells were functionally strictly normal: engulfment, nitroblue tetrazolium (NBT) reduction test, induced iodination, and oxygen consumption were normal. The authors discuss the importance of post-synthetic modifications of the muted enzymes and their repercussions on the enzyme characteristics."}
{"id": "PMID:235391", "title": "Changes in oxygen delivery during hemodialysis.", "content": "The effect of hemodialysis on oxygen delivery has been assessed in nine patients. During hemodialysis the arterial PO2 decreased from 76.89 mm Hg to 69.03 mm Hg. There was also an increase in pH from 7.39 to 7.49 which resulted in an increase in the affinity of the blood for oxygen. In the absence of compensatory changes this could result in a 17.9% decrease in oxygen delivery. This could be hazardous in patients who are already anemic particularly in the presence of cardiac or respiratory insufficiency.", "contents": "Changes in oxygen delivery during hemodialysis. The effect of hemodialysis on oxygen delivery has been assessed in nine patients. During hemodialysis the arterial PO2 decreased from 76.89 mm Hg to 69.03 mm Hg. There was also an increase in pH from 7.39 to 7.49 which resulted in an increase in the affinity of the blood for oxygen. In the absence of compensatory changes this could result in a 17.9% decrease in oxygen delivery. This could be hazardous in patients who are already anemic particularly in the presence of cardiac or respiratory insufficiency."}
{"id": "PMID:235394", "title": "Fetal acquisition and neonatal elimination of a large amount of salicylate. Study of a neonate whose mother regularly took therapeutic doses of aspirin during pregnancy.", "content": "The purpose of this study was to determine the amount of salicylate acquired by a newborn infant from a mother who took 6.5 gm of aspirin a day during her entire pregnancy, and to characterize the kinetics of salicylate elimination by the infant. This healthy female infant was born with a salicylic acid concentration of 25 mg/100 ml plasma and 75 mg/kg body weight. The drug was eliminated during the first 5 days of life, primarily in the form of salicyluric acid. Salicylate elimination was relatively slower than in normal adults, but more rapid than in newborn infants of mothers who had taken only one small dose of aspirin shortly before delivery. The apparent in vivo KM and Vmax for salicylurate formation, on a body weight basis, were at the adult level. The slower elimination of salicylate (relative to adults) by the infant was due to immaturity of the glucuronidation and renal excretory pathways.", "contents": "Fetal acquisition and neonatal elimination of a large amount of salicylate. Study of a neonate whose mother regularly took therapeutic doses of aspirin during pregnancy. The purpose of this study was to determine the amount of salicylate acquired by a newborn infant from a mother who took 6.5 gm of aspirin a day during her entire pregnancy, and to characterize the kinetics of salicylate elimination by the infant. This healthy female infant was born with a salicylic acid concentration of 25 mg/100 ml plasma and 75 mg/kg body weight. The drug was eliminated during the first 5 days of life, primarily in the form of salicyluric acid. Salicylate elimination was relatively slower than in normal adults, but more rapid than in newborn infants of mothers who had taken only one small dose of aspirin shortly before delivery. The apparent in vivo KM and Vmax for salicylurate formation, on a body weight basis, were at the adult level. The slower elimination of salicylate (relative to adults) by the infant was due to immaturity of the glucuronidation and renal excretory pathways."}
{"id": "PMID:235395", "title": "Antiarrhythmic activity of four pteridine compounds in ouabain intoxication.", "content": "The antiarrhythmic effects of 4 pteridine analogues, 2 of which are potassium-sparing diuretics, triamterene (2, 4, 7-triamino-6-phenylpteridine) and [2-phenyl-4, 7 diaminopteridine-6-(N-diethylaminoethyl) carboxamide] and 2 of which have no diuretic effects [2-phenyl-4, 7-diaminopteridine-6-(N-2-hydroxyethyl) carboxamide], on ouabain-induced ventricular tachycardia in intact pentobarbital-anesthetized dogs were investigated. Ouabain was given as a continuous infusion 2 mug/kg/min intravenously until 5 min after the onset of a sustained ventricular tachycardia. It was found that both 6-(N-dimethylaminopropyl) and 6-(N-diethylaminoethyl) carboxamide derivates of the pteridine had a significant protective effect against ouabain-induced ventricular tachycardia in dogs that had been pretreated with a dose of 5 mg/kg intravenously. At this dose the 2 pteridine compounds with diuretic activity exhibited a transient antiarrhythmic effect in abolishing the ouabain-induced ventricular tachycardia while those without diuretic properties failed to suppress the ventricular tachycardia.", "contents": "Antiarrhythmic activity of four pteridine compounds in ouabain intoxication. The antiarrhythmic effects of 4 pteridine analogues, 2 of which are potassium-sparing diuretics, triamterene (2, 4, 7-triamino-6-phenylpteridine) and [2-phenyl-4, 7 diaminopteridine-6-(N-diethylaminoethyl) carboxamide] and 2 of which have no diuretic effects [2-phenyl-4, 7-diaminopteridine-6-(N-2-hydroxyethyl) carboxamide], on ouabain-induced ventricular tachycardia in intact pentobarbital-anesthetized dogs were investigated. Ouabain was given as a continuous infusion 2 mug/kg/min intravenously until 5 min after the onset of a sustained ventricular tachycardia. It was found that both 6-(N-dimethylaminopropyl) and 6-(N-diethylaminoethyl) carboxamide derivates of the pteridine had a significant protective effect against ouabain-induced ventricular tachycardia in dogs that had been pretreated with a dose of 5 mg/kg intravenously. At this dose the 2 pteridine compounds with diuretic activity exhibited a transient antiarrhythmic effect in abolishing the ouabain-induced ventricular tachycardia while those without diuretic properties failed to suppress the ventricular tachycardia."}
{"id": "PMID:235396", "title": "Furosemide binding to human albumin and plasma of nephrotic children.", "content": "The extent and nature of furosemide (F) binding to human albumin (HA) and to the plasma of 6 children with nephrotic syndrome were studied by equilibrium dialysis at 37 degrees C and pH 7.4 with 14C-F. At a total concentration of 3.4 mug/ml (therapeutic range), the unbound fraction of F to 4 gm per 100 ml HA was 2.79 plus or minus 0.35. The degree of binding was relatively constant from 1.8 to 36 mug/ml of F concentration. The percentage of unbound F doubled when total concentration of the drug was increased more than 130 times (1.8 to 245 mug/ml). F has two classes of binding sites (n1 = 1.42, k1 = 5.07 times 10-4 M-minus 1; n2 = 3.4, k2 = 1.58 times 10-4 M-minus 1); interaction with HA involves hydrophobic, ionic, and hydrogen forces. Acetylsalicylic acid (ASA), acetazolamide, diazoxide, phenylbutazone, sulfisoxazole (S), and tolbutamide (T) decreased F binding. Combinations of ASA, S, and T exerted a strong additive displacing effect. The binding of the F metabolite (4-chloro-5-sulfamoylanthranilic acid, CSA) was studied at 1.3 and 2.6 mug/ml. The unbound fraction was 5 times that of F. CSA did not influence F binding. Studies with plasma of 7 healthy adults showed that albumin is the only plasma protein responsible for F binding. The plasma albumin concentration range of the children with nephrotic syndrome was 0.6 to 2.1 gm per 100 ml. There was some correlation between albumin concentration and binding of F (2.8 to 9.6% unbound); this corresponded with findings with HA. Albumin concentrations lower than 2 gm per 100 ml seemed to influence the extent of the unbound fraction of F considerably.", "contents": "Furosemide binding to human albumin and plasma of nephrotic children. The extent and nature of furosemide (F) binding to human albumin (HA) and to the plasma of 6 children with nephrotic syndrome were studied by equilibrium dialysis at 37 degrees C and pH 7.4 with 14C-F. At a total concentration of 3.4 mug/ml (therapeutic range), the unbound fraction of F to 4 gm per 100 ml HA was 2.79 plus or minus 0.35. The degree of binding was relatively constant from 1.8 to 36 mug/ml of F concentration. The percentage of unbound F doubled when total concentration of the drug was increased more than 130 times (1.8 to 245 mug/ml). F has two classes of binding sites (n1 = 1.42, k1 = 5.07 times 10-4 M-minus 1; n2 = 3.4, k2 = 1.58 times 10-4 M-minus 1); interaction with HA involves hydrophobic, ionic, and hydrogen forces. Acetylsalicylic acid (ASA), acetazolamide, diazoxide, phenylbutazone, sulfisoxazole (S), and tolbutamide (T) decreased F binding. Combinations of ASA, S, and T exerted a strong additive displacing effect. The binding of the F metabolite (4-chloro-5-sulfamoylanthranilic acid, CSA) was studied at 1.3 and 2.6 mug/ml. The unbound fraction was 5 times that of F. CSA did not influence F binding. Studies with plasma of 7 healthy adults showed that albumin is the only plasma protein responsible for F binding. The plasma albumin concentration range of the children with nephrotic syndrome was 0.6 to 2.1 gm per 100 ml. There was some correlation between albumin concentration and binding of F (2.8 to 9.6% unbound); this corresponded with findings with HA. Albumin concentrations lower than 2 gm per 100 ml seemed to influence the extent of the unbound fraction of F considerably."}
{"id": "PMID:235398", "title": "Plasma levels and effects of metoprolol on blood pressure and heart rate in hypertensive patients after an acute dose and between two doses during long-term treatment.", "content": "Plasma levels and the effect of orally administered metoprolol on the resting arterial blood pressure and heart rate have been studied during acute and steady-state conditions in patients with mild hypertension. The patients receiving an 80-mg dose had a mean maximum plasma level of about 100 ng/ml plasma in single-dose studies and about 140 ng/ml plasma during steady-state conditions. The corresponding values for the patients on the 50-mg dose were about 60 and 100 ng/ml plasma, respectively. The maximum concentrations were reached 1 hr after administration. After the single dose the elimination half-life of metoprolol in plasma was 4.3 plus or minus 0.7 hr in the patients receiving the 80-mg dose and 3.8 plus or minus 0.3 hr in the other group. The difference was not statistically significant. The elimination half-life in the plasma was about the same in the single-dose study and during steady state in both groups. The morning dose induced a decrease of the systolic blood pressure whereas the diastolic blood pressure was not significantly different from that recorded immediately before administration of metoprolol. For the 80-mg dose the systolic pressure dropped from 167 plus or minus 4 to 146 plus or minus 4 mm Hg in the single dose study and from 160 plus or minus 8 to 140 plus or minus 4 mm Hg at steady state. The corresponding values for the 50-mg dose were 150 plus or minus 3 to 135 plus or minus 3 mm Hg and 144 plus or minus 3 to 138 plus or minus 3 mm Hg, respectively. In experiments with placebo the systolic blood pressure was not significantly changed. There was no correlation between the plasma levels and the effect on the systolic blood pressure. Both doses of metoprolol markedly reduced the heart rate after the single dose as well as at steady state. The effect was linearly related to the logarithm of the plasma concentration, and the relationship was virtually the same as obtained previously for the effect on exercise heart rate in healthy volunteers.", "contents": "Plasma levels and effects of metoprolol on blood pressure and heart rate in hypertensive patients after an acute dose and between two doses during long-term treatment. Plasma levels and the effect of orally administered metoprolol on the resting arterial blood pressure and heart rate have been studied during acute and steady-state conditions in patients with mild hypertension. The patients receiving an 80-mg dose had a mean maximum plasma level of about 100 ng/ml plasma in single-dose studies and about 140 ng/ml plasma during steady-state conditions. The corresponding values for the patients on the 50-mg dose were about 60 and 100 ng/ml plasma, respectively. The maximum concentrations were reached 1 hr after administration. After the single dose the elimination half-life of metoprolol in plasma was 4.3 plus or minus 0.7 hr in the patients receiving the 80-mg dose and 3.8 plus or minus 0.3 hr in the other group. The difference was not statistically significant. The elimination half-life in the plasma was about the same in the single-dose study and during steady state in both groups. The morning dose induced a decrease of the systolic blood pressure whereas the diastolic blood pressure was not significantly different from that recorded immediately before administration of metoprolol. For the 80-mg dose the systolic pressure dropped from 167 plus or minus 4 to 146 plus or minus 4 mm Hg in the single dose study and from 160 plus or minus 8 to 140 plus or minus 4 mm Hg at steady state. The corresponding values for the 50-mg dose were 150 plus or minus 3 to 135 plus or minus 3 mm Hg and 144 plus or minus 3 to 138 plus or minus 3 mm Hg, respectively. In experiments with placebo the systolic blood pressure was not significantly changed. There was no correlation between the plasma levels and the effect on the systolic blood pressure. Both doses of metoprolol markedly reduced the heart rate after the single dose as well as at steady state. The effect was linearly related to the logarithm of the plasma concentration, and the relationship was virtually the same as obtained previously for the effect on exercise heart rate in healthy volunteers."}
{"id": "PMID:235397", "title": "Iodine absorption in burn patients treated topically with povidone-iodine.", "content": "Providone-iodine is used as a topical antimicrobial in burn patients. Although absorption of iodine has been thought to be negligible, several patients have recently been noted with substantial elevations of serum free iodide. Unexplained abnormalities occurred in several of these patients, renal failure, metabolic acidosis, and elevation of serum glutamic oxaloacetic transaminase. It is conceivable that the large iodide loads noted were at least in part responsible for these abnormalities.", "contents": "Iodine absorption in burn patients treated topically with povidone-iodine. Providone-iodine is used as a topical antimicrobial in burn patients. Although absorption of iodine has been thought to be negligible, several patients have recently been noted with substantial elevations of serum free iodide. Unexplained abnormalities occurred in several of these patients, renal failure, metabolic acidosis, and elevation of serum glutamic oxaloacetic transaminase. It is conceivable that the large iodide loads noted were at least in part responsible for these abnormalities."}
{"id": "PMID:235407", "title": "Correlation of psychophysiologic variables with vocational rehabilitation outcome in patients with chronic obstructive pulmonary disease.", "content": "Despite the magnitude of the public health problem presented by respiratory diseases, there have been few studies concerned with vocational rehabilitation (VR) potential of patients with chronic obstructive pulmonary disease (COPD). Certain physiologic variables which show a high degree of relationship to VR success are identified. The three independent variables which most highly correlate with the VR potential of patients with COPD are the percentages predicted for the first-second forced expiratory volume (FEV(1.0)), forced expiratory flow between 25 and 75 percent of the forced vital capacity (FEF(25-75 percent)), and maximum voluntary ventilation (MVV). The mean \"cutting\" percentages for inclusion in VR programs were 50, 27, and 40, respectively. The emotional variables studied do not differentiate potential VR success or failure as clearly as the physiologic factors. The criteria set forth not only can be used by rehabilitation workers but could serve as a basis for future demonstration studies.", "contents": "Correlation of psychophysiologic variables with vocational rehabilitation outcome in patients with chronic obstructive pulmonary disease. Despite the magnitude of the public health problem presented by respiratory diseases, there have been few studies concerned with vocational rehabilitation (VR) potential of patients with chronic obstructive pulmonary disease (COPD). Certain physiologic variables which show a high degree of relationship to VR success are identified. The three independent variables which most highly correlate with the VR potential of patients with COPD are the percentages predicted for the first-second forced expiratory volume (FEV(1.0)), forced expiratory flow between 25 and 75 percent of the forced vital capacity (FEF(25-75 percent)), and maximum voluntary ventilation (MVV). The mean \"cutting\" percentages for inclusion in VR programs were 50, 27, and 40, respectively. The emotional variables studied do not differentiate potential VR success or failure as clearly as the physiologic factors. The criteria set forth not only can be used by rehabilitation workers but could serve as a basis for future demonstration studies."}
{"id": "PMID:235412", "title": "[Optimal time for treating cryptorchism (author's transl)].", "content": "In a ten-year span (1950-1960) a total of 133 patients were operated upon for maldescent of testes. A follow-up enquiry traced 102, of whom 79 were re-examined. Maldescent had been unilateral in 71, bilateral in eight. All of the latter were infertile. In the others the fertility rate was the greater the younger the patient at the time of operation, best results being noted in those operated upon during the first or second year of life. Acquired testicular disorders seemed to play a minor role, while the normally descended contralateral testis was apparently damaged in an as yet undetermined manner (autoantigen-antibody reaction?) It is concluded that the optimal moment for operating on testicular maldescent is (at the latest) the end of the second year of life.", "contents": "[Optimal time for treating cryptorchism (author's transl)]. In a ten-year span (1950-1960) a total of 133 patients were operated upon for maldescent of testes. A follow-up enquiry traced 102, of whom 79 were re-examined. Maldescent had been unilateral in 71, bilateral in eight. All of the latter were infertile. In the others the fertility rate was the greater the younger the patient at the time of operation, best results being noted in those operated upon during the first or second year of life. Acquired testicular disorders seemed to play a minor role, while the normally descended contralateral testis was apparently damaged in an as yet undetermined manner (autoantigen-antibody reaction?) It is concluded that the optimal moment for operating on testicular maldescent is (at the latest) the end of the second year of life."}
{"id": "PMID:235413", "title": "[Endocrine and morphological investigation in undescended testis (author's transl)].", "content": "Determination of the basal and LH-RH-stimulated luteinizing hormone (LH) levels as well as testicular morphology in patients with surgically treated (n equals 112) and non-treated (n equal 96) undescended testes gave the following results: Unilateral of bilateral undescended testes are probably a form of primary, secondary or tertiary hypogonadism. In a high percentage abnormal basal and stimulated serum-LH values can be demonstrated. The testosterone values are within normal limits. The gonadal tissue damage in the abnormally situated testes of prepubertal boys seem to be congenital. With increasing duration of the malposition, particularly after the onset of puberty, a secondary tissue degeneration in the dystopic testis occurs. The damaging influence on the testicular tissue caused by the abnormal position seems to take place mostly at the end of prepuberty. A decrease in the number of spermatogonia in the tubuli of dystopic testes during the first 2 years of life is physiological. A surgical repositioning of the dystopic testis into the scrotum within the first 2 years of life is not indicated. Damage of gonadal tissue in the scrotal testis caused by the dystopic testis in unilateral maldescent could not be demonstrated. The optimal space for orchidopexy is between the third and fifth year of life.", "contents": "[Endocrine and morphological investigation in undescended testis (author's transl)]. Determination of the basal and LH-RH-stimulated luteinizing hormone (LH) levels as well as testicular morphology in patients with surgically treated (n equals 112) and non-treated (n equal 96) undescended testes gave the following results: Unilateral of bilateral undescended testes are probably a form of primary, secondary or tertiary hypogonadism. In a high percentage abnormal basal and stimulated serum-LH values can be demonstrated. The testosterone values are within normal limits. The gonadal tissue damage in the abnormally situated testes of prepubertal boys seem to be congenital. With increasing duration of the malposition, particularly after the onset of puberty, a secondary tissue degeneration in the dystopic testis occurs. The damaging influence on the testicular tissue caused by the abnormal position seems to take place mostly at the end of prepuberty. A decrease in the number of spermatogonia in the tubuli of dystopic testes during the first 2 years of life is physiological. A surgical repositioning of the dystopic testis into the scrotum within the first 2 years of life is not indicated. Damage of gonadal tissue in the scrotal testis caused by the dystopic testis in unilateral maldescent could not be demonstrated. The optimal space for orchidopexy is between the third and fifth year of life."}
{"id": "PMID:235416", "title": "Participation of NADPH-cytochrome C reductase in thyroid hormone biosynthesis.", "content": "Purified rat liver NADPH-cytochrome c reductase supports iodination of tyrosine in a system including NADPH, cytochrome c and thyroid perioxidase. Catalase inhibits the iodination of tyrosine, while superoxide dismutase has no effect. Antibody developed in the rabbit against purified rat liver NADPH-cytochrome c reductase inhibits both reduction of cytochrome c and tyrosine iodination supported by the enzyme. The antibody forms a single precipitation line with thyroid extract, and inhibits NADPH cytochrome c reductase activity of the thyroid. The antibody partially inhibits iodination in a thyroid mitochondrial-microsomal fraction, but does not inhibit NADH-dependent iodination. The immunochemical studies indicate the participation of NADPH-cytochrome c reductase in thyroidal H2O generation, and the independent existence of NADPH-dependent and NADH-dependent H2O2 generation mechanisms in the thyroid.", "contents": "Participation of NADPH-cytochrome C reductase in thyroid hormone biosynthesis. Purified rat liver NADPH-cytochrome c reductase supports iodination of tyrosine in a system including NADPH, cytochrome c and thyroid perioxidase. Catalase inhibits the iodination of tyrosine, while superoxide dismutase has no effect. Antibody developed in the rabbit against purified rat liver NADPH-cytochrome c reductase inhibits both reduction of cytochrome c and tyrosine iodination supported by the enzyme. The antibody forms a single precipitation line with thyroid extract, and inhibits NADPH cytochrome c reductase activity of the thyroid. The antibody partially inhibits iodination in a thyroid mitochondrial-microsomal fraction, but does not inhibit NADH-dependent iodination. The immunochemical studies indicate the participation of NADPH-cytochrome c reductase in thyroidal H2O generation, and the independent existence of NADPH-dependent and NADH-dependent H2O2 generation mechanisms in the thyroid."}
{"id": "PMID:235417", "title": "Release of vasopressin by angiotensin II.", "content": "To test the hypothesis that angiotensin II releases antidiuretic hormone (ADH) after injection into ventricular cerebrospinal fluid, conscious adult male Sprague-Dawley rats with a lateral cerebroventricular cannula received an intraventricular injection of 0, 10, 50, or 100 ng angiotensin II. Trunk blood was collected 90 seconds later for radioimmunoassay of ADH. Plasma ADH, pg/ml (mean plus or minus S. E.), for the four dose levels were 2.8 plus or minus 0.7, 9.6 plus or minus 2.5, 22.6 plus or minus 5.6 and 25.0 plus or minus 5.0, respectively. The increases produced by angiotensin were statistically significant (p smaller than 0.05). Plasma ADH of the 10 ng group was intermediate between control and the two highest angiotensin doses (p smaller than 0.05), suggesting a dose-response relationship. These data provide direct evidence that angiotensin releases ADH by central mechanisms.", "contents": "Release of vasopressin by angiotensin II. To test the hypothesis that angiotensin II releases antidiuretic hormone (ADH) after injection into ventricular cerebrospinal fluid, conscious adult male Sprague-Dawley rats with a lateral cerebroventricular cannula received an intraventricular injection of 0, 10, 50, or 100 ng angiotensin II. Trunk blood was collected 90 seconds later for radioimmunoassay of ADH. Plasma ADH, pg/ml (mean plus or minus S. E.), for the four dose levels were 2.8 plus or minus 0.7, 9.6 plus or minus 2.5, 22.6 plus or minus 5.6 and 25.0 plus or minus 5.0, respectively. The increases produced by angiotensin were statistically significant (p smaller than 0.05). Plasma ADH of the 10 ng group was intermediate between control and the two highest angiotensin doses (p smaller than 0.05), suggesting a dose-response relationship. These data provide direct evidence that angiotensin releases ADH by central mechanisms."}
{"id": "PMID:235418", "title": "Amino terminal residue heterogeneity of bovine and ovine growth hormones as revealed by polyacrylamide gel electrophoresis.", "content": "Prolonged electrophoresis (4 to 16 h) of bovine and ovine growth hormones on analytical polyacrylamide gels in Tris-EDTA-borate buffers of pH 7.6 to 8.1 resulted in the separation of alanyl, phenylalanyl, and methionyl terminal polypeptide chains of these hormones similar to that obtained by isoelectric focusing in Ampholine pH gradients. Their relative anodic mobilities were methionyl greater than phenylalanyl greater than alanyl. The mobilities of the respective monomers were inversely related to their isoionic points as determined by isoelectric focusing in Ampholine pH gradients. The resolution of the different monomers is attributed to differences in the dissociation constants of the amino groups of the alanyl, phenylalanyl and methionyl terminal residues. Rat growth hormone, which consists of monomers with only a phenylalanyl amino terminus, did not display heterogeneity on gel electrophoresis. The applicability of employing polyacrylamide gel electrophoresis for the assessing of amino terminal residue heterogeneity is noted.", "contents": "Amino terminal residue heterogeneity of bovine and ovine growth hormones as revealed by polyacrylamide gel electrophoresis. Prolonged electrophoresis (4 to 16 h) of bovine and ovine growth hormones on analytical polyacrylamide gels in Tris-EDTA-borate buffers of pH 7.6 to 8.1 resulted in the separation of alanyl, phenylalanyl, and methionyl terminal polypeptide chains of these hormones similar to that obtained by isoelectric focusing in Ampholine pH gradients. Their relative anodic mobilities were methionyl greater than phenylalanyl greater than alanyl. The mobilities of the respective monomers were inversely related to their isoionic points as determined by isoelectric focusing in Ampholine pH gradients. The resolution of the different monomers is attributed to differences in the dissociation constants of the amino groups of the alanyl, phenylalanyl and methionyl terminal residues. Rat growth hormone, which consists of monomers with only a phenylalanyl amino terminus, did not display heterogeneity on gel electrophoresis. The applicability of employing polyacrylamide gel electrophoresis for the assessing of amino terminal residue heterogeneity is noted."}
{"id": "PMID:235419", "title": "Study of the mechanism of thyroid hormone secretion in an in vitro model system: indirect evidence for fusion of lysosomes with thyroglobulin liposomes.", "content": "The interaction between [131I]-thyroglobulin liposomes and thyroidal lysosomes was used as an in vitro model system for analyzing the relation of colloid droplets to lysosomes in follicular cells. The rates of hydrolysis of [131I]-thyroglobulin in a liposome-lysosome system (Lipo-Lyso system) and a thyroglobulin-lysosome system (TG-Lyso system) were compared. Hydrolysis of thyroglobulin in the Lipo-Lyso system increased hyperbolically and was greater than that in the TG-Lyso system for about 10 h. Liposomal thyroglobulin was not degraded by the 20,000 X g supernatant obtained on disruption of the lysosomal fraction. On varying the pH of the incubation medium, the highest activity was observed under acidic conditions in both systems. Under neutral or weakly alkaline conditions, the Lipo-Lyso system still showed 50% of the maximal hydrolytic activity, while the TG-Lyso system showed no activity. ATP and anaerobic conditions had no effect on either system. Cysteine (5 X 10-2M) and p-chloromercuribenzene sulfonic acid (PCMBS, 10-3 M) had not influence on hydrolysis in the Lipo-Lyso system, but in the TG-Lyso system cysteine greatly increased, and PCMBS significantly reduced the rate of hydrolysis. Dibutyryl cyclic AMP had no effect. Chlorpromazine (Cpz) decreased liposomal thyroglobulin hydrolysis in a concentration-dependent manner. In the TG-Lyso system, concentrations of 10-4M Cpz had no effect. These results strongly suggest that liposomes rapidly fused with lysosomes, providing optimal conditions for hydrolysis of thyroglobulin.", "contents": "Study of the mechanism of thyroid hormone secretion in an in vitro model system: indirect evidence for fusion of lysosomes with thyroglobulin liposomes. The interaction between [131I]-thyroglobulin liposomes and thyroidal lysosomes was used as an in vitro model system for analyzing the relation of colloid droplets to lysosomes in follicular cells. The rates of hydrolysis of [131I]-thyroglobulin in a liposome-lysosome system (Lipo-Lyso system) and a thyroglobulin-lysosome system (TG-Lyso system) were compared. Hydrolysis of thyroglobulin in the Lipo-Lyso system increased hyperbolically and was greater than that in the TG-Lyso system for about 10 h. Liposomal thyroglobulin was not degraded by the 20,000 X g supernatant obtained on disruption of the lysosomal fraction. On varying the pH of the incubation medium, the highest activity was observed under acidic conditions in both systems. Under neutral or weakly alkaline conditions, the Lipo-Lyso system still showed 50% of the maximal hydrolytic activity, while the TG-Lyso system showed no activity. ATP and anaerobic conditions had no effect on either system. Cysteine (5 X 10-2M) and p-chloromercuribenzene sulfonic acid (PCMBS, 10-3 M) had not influence on hydrolysis in the Lipo-Lyso system, but in the TG-Lyso system cysteine greatly increased, and PCMBS significantly reduced the rate of hydrolysis. Dibutyryl cyclic AMP had no effect. Chlorpromazine (Cpz) decreased liposomal thyroglobulin hydrolysis in a concentration-dependent manner. In the TG-Lyso system, concentrations of 10-4M Cpz had no effect. These results strongly suggest that liposomes rapidly fused with lysosomes, providing optimal conditions for hydrolysis of thyroglobulin."}
{"id": "PMID:235420", "title": "Triiodothyronine binding to liver nuclear solubilized proteins in vitro.", "content": "Nuclear proteins extracted from purified nuclei with 0.4M KCl at pH 7.4 OR 8.5 are able to bind L-triiodothyronine (T3) giving rise to nuclear thyroid hormone binding protein-T3 (NTBP-T3) complexes. Binding is maximum in 3 h at 20 C. It is thermolabile even at 36 C, inhibited by p-hydroxymercuribenzoate and markedly enhanced by dithiothreitol. Optimum pH is between 7.8 and 8.5. Divalent cations are not necessary. The NTBP-T3 complex exhibits similar anodal electrophoretic migration in polyacrylamide gel at pH 8.5, whether formed in vivo or in vitro. Scatchard plots obtained with various amounts of T3 from 0.15 nM TO 0.15 MUM and either unlabeled nuclear proteins or in vivo formed NTBP-[125I]-T3 complexes, give apparent association constants K-a of 0.2 X 10-10 M minus at pH 7.4 and 0.8 X 10-10 M minus 1 at pH 8.5. Capacity is about 0.5 pmol T3 per mg protein or 800 pg/g liver. The presence of dithiothreitol markedly enhances the Ka. The nuclear binding sites are not highly specific for L-T3 since they are able to bind D-T3 with almost equal affinity and triiodothyroacetic acid with a higher affinity. L-thyroxine (T4) can also displace L-T3 but with about 10-fold lesser effectiveness. Nuclear binding proteins of low capacity and high affinity have been demonstrated in vitro. The NTBP-T3 complexes formed in vivo, with whole nuclei, or in vitro are indistinguishable.", "contents": "Triiodothyronine binding to liver nuclear solubilized proteins in vitro. Nuclear proteins extracted from purified nuclei with 0.4M KCl at pH 7.4 OR 8.5 are able to bind L-triiodothyronine (T3) giving rise to nuclear thyroid hormone binding protein-T3 (NTBP-T3) complexes. Binding is maximum in 3 h at 20 C. It is thermolabile even at 36 C, inhibited by p-hydroxymercuribenzoate and markedly enhanced by dithiothreitol. Optimum pH is between 7.8 and 8.5. Divalent cations are not necessary. The NTBP-T3 complex exhibits similar anodal electrophoretic migration in polyacrylamide gel at pH 8.5, whether formed in vivo or in vitro. Scatchard plots obtained with various amounts of T3 from 0.15 nM TO 0.15 MUM and either unlabeled nuclear proteins or in vivo formed NTBP-[125I]-T3 complexes, give apparent association constants K-a of 0.2 X 10-10 M minus at pH 7.4 and 0.8 X 10-10 M minus 1 at pH 8.5. Capacity is about 0.5 pmol T3 per mg protein or 800 pg/g liver. The presence of dithiothreitol markedly enhances the Ka. The nuclear binding sites are not highly specific for L-T3 since they are able to bind D-T3 with almost equal affinity and triiodothyroacetic acid with a higher affinity. L-thyroxine (T4) can also displace L-T3 but with about 10-fold lesser effectiveness. Nuclear binding proteins of low capacity and high affinity have been demonstrated in vitro. The NTBP-T3 complexes formed in vivo, with whole nuclei, or in vitro are indistinguishable."}
{"id": "PMID:235425", "title": "Properties of a DNA-adenylate complex formed in the reaction between mammalian DNA ligase I and DNA containing single-strand breaks.", "content": "The major DNA ligase from calf thymus (mammalian DNA ligase I) forms a covalent enzyme-AMP complex on incubation with ATP [S\u00f6derh\u00e4ll & Lindahl, J. Biol. Chem. 248, 672-675, (1973)]. The reaction of this complex with DNA has now been studied. When the ligase-adenylate complex is incubated at 0 degrees C for short time periods with DNA containing single-strand breaks, a DNA-AMP complex can be isolated from the reaction mixture by isopycnic centrifugation in CsCl. Incubation at pH 6.5 increased the amount of DNA-AMP complex that could be isolated 10-20-fold relative to that obtained at pH 7.4. Under the same conditions, incubation of the ligase-AMP complex with DNA free from single-strand breaks did not lead to detectable DNA-AMP formation. The DNA-AMP complex was resistant to treatment with dilute acid and alkali indicating the presence of a covalent linkage. Further, this complex was sensitive to DNase but resistant to pronase and RNase. Free AMP was released on further incubation of the isolated DNA-AMP complex with thymus DNA ligase I and Mg2+, suggesting that the complex is a reaction intermediate. Degradation of the DNA-AMP complex with several reagent enzymes indicated that the AMP residues were bound at the 5' ends of the single-strand breaks in DNA by pyrophosphate bonds.", "contents": "Properties of a DNA-adenylate complex formed in the reaction between mammalian DNA ligase I and DNA containing single-strand breaks. The major DNA ligase from calf thymus (mammalian DNA ligase I) forms a covalent enzyme-AMP complex on incubation with ATP [S\u00f6derh\u00e4ll & Lindahl, J. Biol. Chem. 248, 672-675, (1973)]. The reaction of this complex with DNA has now been studied. When the ligase-adenylate complex is incubated at 0 degrees C for short time periods with DNA containing single-strand breaks, a DNA-AMP complex can be isolated from the reaction mixture by isopycnic centrifugation in CsCl. Incubation at pH 6.5 increased the amount of DNA-AMP complex that could be isolated 10-20-fold relative to that obtained at pH 7.4. Under the same conditions, incubation of the ligase-AMP complex with DNA free from single-strand breaks did not lead to detectable DNA-AMP formation. The DNA-AMP complex was resistant to treatment with dilute acid and alkali indicating the presence of a covalent linkage. Further, this complex was sensitive to DNase but resistant to pronase and RNase. Free AMP was released on further incubation of the isolated DNA-AMP complex with thymus DNA ligase I and Mg2+, suggesting that the complex is a reaction intermediate. Degradation of the DNA-AMP complex with several reagent enzymes indicated that the AMP residues were bound at the 5' ends of the single-strand breaks in DNA by pyrophosphate bonds."}
{"id": "PMID:235426", "title": "18-Hydroxylation of deoxycorticosterone by reconstituted systems from rat and bovine adrenals.", "content": "18-Hydroxylation of deoxycorticosterone was studies with rat or bovine adrenal mitochondria or with reconstituted systems obtained from these fractions. The reconstituted systems consisted of a partially purified preparation of cytochrome P-450 from rat adrenals and a partially purified NADPH-cytochrome P450 reductase preparation from bovine adrenals. In some experimenta a soluble cytochrome P-450 fraction from bovine adrenals was used. Adrenodoxine and adrenodoxine reductase were shown to be the active components of the NADPH-cytochrome P-450 reductase preparation. Optimal assay conditions were determined for 18-hydroxylation by the crude mitochondrial fraction as well as by the reconstituted systems. In the presence of excess NADPH-cytochrome P-450 reductase fraction, the rate of 18-hydroxylation was linear with time and with the amount of cytochrome P-450. In incubations with intact rat adrenal mitochondria to which Ca2+ and an excess NADPH had been added, NADPH-cytochrome P-450 reductase increased the rate of 18-hydroxylation about 100%, indicating that NADPH-cytochrome P-45o reductase was to some extent rate-limiting. The rate of 18-hydroxylation of deoxycorticosterone by the reconstituted system as well as by intact mitochondrial fraction was much higher than the rat of 18-hydroxylation of corticosterone and progesterone. When the cytochrome P-450 preparation from rat adrenals in the reconstituted system was substituted for cytochrome P-450 from bovine adrenals, the rate of 18-hydroxylation decreased considerably. Under all experimental conditions, the 18-hydroxylation of deoxycorticosterone occurred with a concomitant and efficient 11beta-hydroxylation. Provided the source of cytochrome P-450 was the same, the ratio between 11beta- and 18hydroxylation was constant under all conditions and was not significantly different in the presence of metopirone, carbon monoxide, cytochrome c or different steroids. It is suggested that identical or at least very similar types of cytochrome P-450 are involved in 11beta- and 18-hydroxylation of deoxycorticosterone.", "contents": "18-Hydroxylation of deoxycorticosterone by reconstituted systems from rat and bovine adrenals. 18-Hydroxylation of deoxycorticosterone was studies with rat or bovine adrenal mitochondria or with reconstituted systems obtained from these fractions. The reconstituted systems consisted of a partially purified preparation of cytochrome P-450 from rat adrenals and a partially purified NADPH-cytochrome P450 reductase preparation from bovine adrenals. In some experimenta a soluble cytochrome P-450 fraction from bovine adrenals was used. Adrenodoxine and adrenodoxine reductase were shown to be the active components of the NADPH-cytochrome P-450 reductase preparation. Optimal assay conditions were determined for 18-hydroxylation by the crude mitochondrial fraction as well as by the reconstituted systems. In the presence of excess NADPH-cytochrome P-450 reductase fraction, the rate of 18-hydroxylation was linear with time and with the amount of cytochrome P-450. In incubations with intact rat adrenal mitochondria to which Ca2+ and an excess NADPH had been added, NADPH-cytochrome P-450 reductase increased the rate of 18-hydroxylation about 100%, indicating that NADPH-cytochrome P-45o reductase was to some extent rate-limiting. The rate of 18-hydroxylation of deoxycorticosterone by the reconstituted system as well as by intact mitochondrial fraction was much higher than the rat of 18-hydroxylation of corticosterone and progesterone. When the cytochrome P-450 preparation from rat adrenals in the reconstituted system was substituted for cytochrome P-450 from bovine adrenals, the rate of 18-hydroxylation decreased considerably. Under all experimental conditions, the 18-hydroxylation of deoxycorticosterone occurred with a concomitant and efficient 11beta-hydroxylation. Provided the source of cytochrome P-450 was the same, the ratio between 11beta- and 18hydroxylation was constant under all conditions and was not significantly different in the presence of metopirone, carbon monoxide, cytochrome c or different steroids. It is suggested that identical or at least very similar types of cytochrome P-450 are involved in 11beta- and 18-hydroxylation of deoxycorticosterone."}
{"id": "PMID:235427", "title": "Extracellular enzyme system utilized by the fungus Sporotrichum pulverulentum (Chrysosporium lignorum) for the breakdown of cellulose. 1. Separation, purification and physico-chemical characterization of five endo-1,4-beta-glucanases.", "content": "Five endo-1,4-beta-glucanases (EC 3.2.1.4) have been separated from culture solutions OF THE ROT FUNGUS Sporotrichum pulverulentum (formerly called Chrysosporium lignorum) grown on powder cellulose as the sole carbon source. They have been extensively purified and characterized with regard to some physicochemical properties. The purifications have been carried out on a quantitative basis, the purity of the enzymes being tested in several ways. After purification they all showed one single protein band in analytical polyacrylamide electrophoresis, on dodecyl-sulphate gels and in analytical isoelectric focusing on flat-bed polyacrylamide gels. One exo-1,4-beta-glucanase has also been identified in the culture solution and separated from the endo-1,4-beta-glucanases. From the data obtained during the quantitative purification it has been possible to calculate that the ratio of activity between the five endoglucanases T1, T2a, T2b, T3a, and T3b in the culture solutions is 4:1:1:1:1. It has also been calculated that the weight ratio endoglucanase protein to exoglucanase protein is approximately 1:1. Flat-bed isoelectric focusing has been used for the identification of the individual endoglucanases and a new zymogram technique, useful for studies of carbohydrases in general, has been developed. The molecular weights, determined by ultracentrifugation, and calculated on the basis of a knowledge of the amino acid composition and carbohydrate content vary between 28200 and 37500. Small but significant differences in the amino acid compositions of the different endoglucanases have been found. The carbohydrate content varies between 0 and 10.5%, all but one of the enzymes being glycoproteins. For two of these the exact carbohydrate composition has been determined. Enzyme T1 contains 2 glucose and 19 mannose units per enzyme molecule while enzyme T2b contains 5 mannose, 7 galactose, 1 glucose and 1 arabinose unit per molecule.", "contents": "Extracellular enzyme system utilized by the fungus Sporotrichum pulverulentum (Chrysosporium lignorum) for the breakdown of cellulose. 1. Separation, purification and physico-chemical characterization of five endo-1,4-beta-glucanases. Five endo-1,4-beta-glucanases (EC 3.2.1.4) have been separated from culture solutions OF THE ROT FUNGUS Sporotrichum pulverulentum (formerly called Chrysosporium lignorum) grown on powder cellulose as the sole carbon source. They have been extensively purified and characterized with regard to some physicochemical properties. The purifications have been carried out on a quantitative basis, the purity of the enzymes being tested in several ways. After purification they all showed one single protein band in analytical polyacrylamide electrophoresis, on dodecyl-sulphate gels and in analytical isoelectric focusing on flat-bed polyacrylamide gels. One exo-1,4-beta-glucanase has also been identified in the culture solution and separated from the endo-1,4-beta-glucanases. From the data obtained during the quantitative purification it has been possible to calculate that the ratio of activity between the five endoglucanases T1, T2a, T2b, T3a, and T3b in the culture solutions is 4:1:1:1:1. It has also been calculated that the weight ratio endoglucanase protein to exoglucanase protein is approximately 1:1. Flat-bed isoelectric focusing has been used for the identification of the individual endoglucanases and a new zymogram technique, useful for studies of carbohydrases in general, has been developed. The molecular weights, determined by ultracentrifugation, and calculated on the basis of a knowledge of the amino acid composition and carbohydrate content vary between 28200 and 37500. Small but significant differences in the amino acid compositions of the different endoglucanases have been found. The carbohydrate content varies between 0 and 10.5%, all but one of the enzymes being glycoproteins. For two of these the exact carbohydrate composition has been determined. Enzyme T1 contains 2 glucose and 19 mannose units per enzyme molecule while enzyme T2b contains 5 mannose, 7 galactose, 1 glucose and 1 arabinose unit per molecule."}
{"id": "PMID:235428", "title": "Extracellular enzyme system utilized by the fungus Sporotrichum pulverulentum (Chrysosporium lignorum) for the breakdown of cellulose. 3. Purification and physico-chemical characterization of an exo-1,4-beta-glucanase.", "content": "An exo-1,4-beta-glucanase from culture solution of the rot fungus Sporotrichum pulverulentum (formerly called Chrysosporium lignorum) grown on powder cellulose as the sole carbon source has been extensively purified and characterized with respect to some physico-chemical properties. The purification has been carried out in a five-step procedure comprising chromatography on DEAE-Sephadex, gel filtration on polyacrylamide P-150, activation on a Dowex 2-X8 anion exchanger, chromatography on Concanavalin A-Sepharose and chromatography on SP-Sephadex. The purified enzyme was found to be pure and homogeneous by analytical polyacrylamide electrophoresis, by electrophoresis on dodecylsulphate gels and by analytical polyacrylamide electrophoresis, by electrophoresis on dodecylsulphate gels and by analytical isoelectric focusing. A single symmetrical peak was obtained with the free zone electrophoresis method. The purification factor is about 15 and the yield of exo-1,4-beta-glucanase activity 7%. After purification, the enzyme showed no viscosity-decreasing activity towards carboxymethyl-cellulose solutions. The exo-1,4-beta-glucanase was isoelectric at pH 4.3 (4 degrees C). A molecular weight of 48600 was calculated on the basis of a knowledge of the partial specific volume, ultracentrifugation data and the amino acid composition. The enzyme contained no carbohydrate.", "contents": "Extracellular enzyme system utilized by the fungus Sporotrichum pulverulentum (Chrysosporium lignorum) for the breakdown of cellulose. 3. Purification and physico-chemical characterization of an exo-1,4-beta-glucanase. An exo-1,4-beta-glucanase from culture solution of the rot fungus Sporotrichum pulverulentum (formerly called Chrysosporium lignorum) grown on powder cellulose as the sole carbon source has been extensively purified and characterized with respect to some physico-chemical properties. The purification has been carried out in a five-step procedure comprising chromatography on DEAE-Sephadex, gel filtration on polyacrylamide P-150, activation on a Dowex 2-X8 anion exchanger, chromatography on Concanavalin A-Sepharose and chromatography on SP-Sephadex. The purified enzyme was found to be pure and homogeneous by analytical polyacrylamide electrophoresis, by electrophoresis on dodecylsulphate gels and by analytical polyacrylamide electrophoresis, by electrophoresis on dodecylsulphate gels and by analytical isoelectric focusing. A single symmetrical peak was obtained with the free zone electrophoresis method. The purification factor is about 15 and the yield of exo-1,4-beta-glucanase activity 7%. After purification, the enzyme showed no viscosity-decreasing activity towards carboxymethyl-cellulose solutions. The exo-1,4-beta-glucanase was isoelectric at pH 4.3 (4 degrees C). A molecular weight of 48600 was calculated on the basis of a knowledge of the partial specific volume, ultracentrifugation data and the amino acid composition. The enzyme contained no carbohydrate."}
{"id": "PMID:235429", "title": "Purine nucleoside phosphorylase from Escherichia coli and Salmonella typhimurium. Purification and some properties.", "content": "The purine nucleoside phosphorylases from Escherichia coli and from Salmonella typhimurium have been purified to electrophoretic homogeneity and crystallized. Comparative studies revealed that the two enzymes are very much alike. They obey simple Michaelis-Menten kinetics for their substrates with the exception of phosphate for which they show negative cooperativity. Gel filtration on Sephadex G-200 of the native enzymes revealed a molecular weight for both enzymes of 138000 plus or minus 10%. By use of dodecylsulphate gel electrophoresis a subunit molecular weight of 23700 plus or minus 5% was determined, suggesting that both enzymes consist of six subunits of equal molecular weight. When the subunits were partially crosslinked with dimethyl suberimidate before dodecylsulphate electrophoresis six protein bands were observed in agreement with the proposed oligomeric state of the enzyme, consisting of six subunits of equal molecular weight. Analysis of the amino acid composition also indicates that the subunits are identical. 6M guanidinium chloride dissociates the enzymes; association experiments with native and succinylated enzymes suggested that only the hexameric form is active. Both enzymes could be dissociated into subunits by p-chloromercuribenzoate; this dissociation is prevented by the substrates: the nucleosides, the pentose 1-phosphates, and mixtures of phosphate and purine bases.", "contents": "Purine nucleoside phosphorylase from Escherichia coli and Salmonella typhimurium. Purification and some properties. The purine nucleoside phosphorylases from Escherichia coli and from Salmonella typhimurium have been purified to electrophoretic homogeneity and crystallized. Comparative studies revealed that the two enzymes are very much alike. They obey simple Michaelis-Menten kinetics for their substrates with the exception of phosphate for which they show negative cooperativity. Gel filtration on Sephadex G-200 of the native enzymes revealed a molecular weight for both enzymes of 138000 plus or minus 10%. By use of dodecylsulphate gel electrophoresis a subunit molecular weight of 23700 plus or minus 5% was determined, suggesting that both enzymes consist of six subunits of equal molecular weight. When the subunits were partially crosslinked with dimethyl suberimidate before dodecylsulphate electrophoresis six protein bands were observed in agreement with the proposed oligomeric state of the enzyme, consisting of six subunits of equal molecular weight. Analysis of the amino acid composition also indicates that the subunits are identical. 6M guanidinium chloride dissociates the enzymes; association experiments with native and succinylated enzymes suggested that only the hexameric form is active. Both enzymes could be dissociated into subunits by p-chloromercuribenzoate; this dissociation is prevented by the substrates: the nucleosides, the pentose 1-phosphates, and mixtures of phosphate and purine bases."}
{"id": "PMID:235430", "title": "On the mechanism of action of isocitrate lyase.", "content": "1. The enzymes citrate lyase and isocitrate lyase catalyse similar reactions in the cleavage of citrate to acetate plus oxaloacetate and of isocitrate to succinate plus glyoxylate, respectively. 2. Nevertheless, the mechanism of action of each enzyme appears to be different from each other. Citrate lyase is an acyl carrier protein-containing enzyme complex whereas isocitrate lyase is not. The active form of citrate lyase is an acetyl-S-enzyme but that of isocitrate lyase is not a corresponding succinyl-S-enzyme. 3. In contrast to citrate lyase, the isocitrate enzyme is not inhibited by hydroxylamine nor does it acquire label if treated with appropriately labelled radioactive substrate. 4. Isotopic exchange experiments performed in H18-2O with isocitrate as a substrate produced no labelling in the product succinate. This was shown by mass-spectrometric analysis. 5. The conclusion drawn from these results is that no activation of succinate takes place on the enzyme through transient formation of succinic anhydride or a covalently-linked succinyl-enzyme, derived from this anhydride.", "contents": "On the mechanism of action of isocitrate lyase. 1. The enzymes citrate lyase and isocitrate lyase catalyse similar reactions in the cleavage of citrate to acetate plus oxaloacetate and of isocitrate to succinate plus glyoxylate, respectively. 2. Nevertheless, the mechanism of action of each enzyme appears to be different from each other. Citrate lyase is an acyl carrier protein-containing enzyme complex whereas isocitrate lyase is not. The active form of citrate lyase is an acetyl-S-enzyme but that of isocitrate lyase is not a corresponding succinyl-S-enzyme. 3. In contrast to citrate lyase, the isocitrate enzyme is not inhibited by hydroxylamine nor does it acquire label if treated with appropriately labelled radioactive substrate. 4. Isotopic exchange experiments performed in H18-2O with isocitrate as a substrate produced no labelling in the product succinate. This was shown by mass-spectrometric analysis. 5. The conclusion drawn from these results is that no activation of succinate takes place on the enzyme through transient formation of succinic anhydride or a covalently-linked succinyl-enzyme, derived from this anhydride."}
{"id": "PMID:235431", "title": "[Transfer of glucose from UDP-glucose in microsomal membranes of rat hepatocytes (author's transl)].", "content": "Microsomal preparations from rat liver mediate transfer of glucosyl units from UDP-glucose to three different kinds of acceptors: an endogenous glycoprotein, exogenous glycogen and collagen. Both glucosyl transferases work at acidic pH, 6.5 for transfer on endogeneous acceptor and glycogen and at pH 5.5 for transfer on collagen. None of these enzymes require divalent cations for activity. While transfers on endogenous acceptor and glycogen are inhibited by the presence of a non-ionic detergent, Triton X-100, the transfer on collagen is activated by the same detergent. Glycogen-synthase activity requires glucose 6-phosphate at an optimal concentration of 1 mM. The Km values for UDP-glucose are respectively: 0.5 mM, 0.33 mM, and 1 mM for transfer on endogenous acceptor, glycogen and collagen. Characterisation of the product indicates that a protein-bound alpha1-4 glucan is formed when no primer is added. Enzymatic and acidic hydrolyses of radioactive glycogen and collagen show only glucose as a radioactive sugar identified by thin layer chromatography on cellulose. Pre-treatment of microsomal membranes by alpha-amylase demonstrates that glucosyltransferases are not adsorbed on endogenous glycogen and seem to be really membranous enzymes.", "contents": "[Transfer of glucose from UDP-glucose in microsomal membranes of rat hepatocytes (author's transl)]. Microsomal preparations from rat liver mediate transfer of glucosyl units from UDP-glucose to three different kinds of acceptors: an endogenous glycoprotein, exogenous glycogen and collagen. Both glucosyl transferases work at acidic pH, 6.5 for transfer on endogeneous acceptor and glycogen and at pH 5.5 for transfer on collagen. None of these enzymes require divalent cations for activity. While transfers on endogenous acceptor and glycogen are inhibited by the presence of a non-ionic detergent, Triton X-100, the transfer on collagen is activated by the same detergent. Glycogen-synthase activity requires glucose 6-phosphate at an optimal concentration of 1 mM. The Km values for UDP-glucose are respectively: 0.5 mM, 0.33 mM, and 1 mM for transfer on endogenous acceptor, glycogen and collagen. Characterisation of the product indicates that a protein-bound alpha1-4 glucan is formed when no primer is added. Enzymatic and acidic hydrolyses of radioactive glycogen and collagen show only glucose as a radioactive sugar identified by thin layer chromatography on cellulose. Pre-treatment of microsomal membranes by alpha-amylase demonstrates that glucosyltransferases are not adsorbed on endogenous glycogen and seem to be really membranous enzymes."}
{"id": "PMID:235432", "title": "Electron-spin resonance of nitrosyl haemoglobins: normal alpha and beta chains and mutants Hb M Iwate and Hb Z\u00fcrich.", "content": "At 77 K the electron spin resonance (ESR) spectra of the NO derivatives of the mutant haemoglobins Hb M Iwate and Hb Zurich as well as of the isolated chains of normal haemoglobin were studied. Two types of ESR spectra differing in the g-value and the hyperfine splitting at gzz were observed. The type II spectrum is characterized by a hyperfine structure at gzz = 2.005 with a splitting constant of deltaH = 23 G (14NO) or 32 G (15NO), respectively. In the type I spectrum the splitting constant of the hyperfine structure at gzz = 2.009  amounts to deltaH = 18 G (14NO) or 23 G (15NO), respectively. In some cases this hyperfine structure is coincident with another one at gxx = 2.064 with nearly identical splitting constant. In addition, the type I spectrum is characterized by an increased ESR absorption at gxx = 2.064. At neutral pH the NO derivatives of the isolated chains as well as of the mutant haemoglobins give rise to a type II spectrum. In correspondence with previous results gained with normal NO haemoglobin, the ESR spectra of the NO-alpha chains and NO-Hb Zurich show a transition to type I in the acid region. This transition is favoured by binding of 2,3-bisphosphoglycerate. On the other hand, the ESR spectra of the NO-beta chains and NO-Hb M Iwate are of the type II also at acid pH. The NO-beta chains show a transition of the ESR spectrum from type II to type I only at alkaline pH. These results indicate that in the tetrameric NO haemoglobin only the alpha chains are responsible for the transition of the ESR spectrum from type II to type I in the acid region. The two types of ESR spectra are interpreted in terms of two kinds of haem-NO complexes differing in the iron-NO and iron-imidazole distances. The type II spectrum is attributed to a complex with a relatively short iron-imidazole distance which is responsible for a weakened sigma-bond in trans position. The type I spectrum arises then from a complex with a larger iron-imidazole bond leading to an approach of the NO molecule to the iron. The influence of the protein conformation upon the iron-imidazole bond length is discussed with regard to the ESR spectra of the mutant NO haemoglobins and considering the influence of agents modifying the protein structure.", "contents": "Electron-spin resonance of nitrosyl haemoglobins: normal alpha and beta chains and mutants Hb M Iwate and Hb Z\u00fcrich. At 77 K the electron spin resonance (ESR) spectra of the NO derivatives of the mutant haemoglobins Hb M Iwate and Hb Zurich as well as of the isolated chains of normal haemoglobin were studied. Two types of ESR spectra differing in the g-value and the hyperfine splitting at gzz were observed. The type II spectrum is characterized by a hyperfine structure at gzz = 2.005 with a splitting constant of deltaH = 23 G (14NO) or 32 G (15NO), respectively. In the type I spectrum the splitting constant of the hyperfine structure at gzz = 2.009  amounts to deltaH = 18 G (14NO) or 23 G (15NO), respectively. In some cases this hyperfine structure is coincident with another one at gxx = 2.064 with nearly identical splitting constant. In addition, the type I spectrum is characterized by an increased ESR absorption at gxx = 2.064. At neutral pH the NO derivatives of the isolated chains as well as of the mutant haemoglobins give rise to a type II spectrum. In correspondence with previous results gained with normal NO haemoglobin, the ESR spectra of the NO-alpha chains and NO-Hb Zurich show a transition to type I in the acid region. This transition is favoured by binding of 2,3-bisphosphoglycerate. On the other hand, the ESR spectra of the NO-beta chains and NO-Hb M Iwate are of the type II also at acid pH. The NO-beta chains show a transition of the ESR spectrum from type II to type I only at alkaline pH. These results indicate that in the tetrameric NO haemoglobin only the alpha chains are responsible for the transition of the ESR spectrum from type II to type I in the acid region. The two types of ESR spectra are interpreted in terms of two kinds of haem-NO complexes differing in the iron-NO and iron-imidazole distances. The type II spectrum is attributed to a complex with a relatively short iron-imidazole distance which is responsible for a weakened sigma-bond in trans position. The type I spectrum arises then from a complex with a larger iron-imidazole bond leading to an approach of the NO molecule to the iron. The influence of the protein conformation upon the iron-imidazole bond length is discussed with regard to the ESR spectra of the mutant NO haemoglobins and considering the influence of agents modifying the protein structure."}
{"id": "PMID:235433", "title": "Protein A from Staphylococcus aureus. Spectropolarimetric and Spectrophotometric studies.", "content": "Protein A, a cell-wall protein from Staphylococcus aureus, has been studied by spectrophotometry and spectropolarimetry. All the four tyrosines are similarily titrated with pK-a equals 10.25. Circular dichroism (CD) spectra show that the conformation of protein A is very stable over a large pH interval (0.99-11.8). The conformation is partly intact even in 6 M guanidine hydrochloride and at 80 degrees C. Protein A contains about 50% alpha-helical structure and 10-20% beta-structures. CD band maxima at 261 and 268 nm are ascribed to transitions in the phenylalanine residues and ellipticities between 275-285 nm to the tyrosine residues. Of the four tyrosines, 3.5 are perturbed by 20% polyethylene glycol, while all of them are perturbed by 20% dimethylsulfoxide. The role of the tyrosines in the reaction with the Fc-region of immunoglobulins is discussed.", "contents": "Protein A from Staphylococcus aureus. Spectropolarimetric and Spectrophotometric studies. Protein A, a cell-wall protein from Staphylococcus aureus, has been studied by spectrophotometry and spectropolarimetry. All the four tyrosines are similarily titrated with pK-a equals 10.25. Circular dichroism (CD) spectra show that the conformation of protein A is very stable over a large pH interval (0.99-11.8). The conformation is partly intact even in 6 M guanidine hydrochloride and at 80 degrees C. Protein A contains about 50% alpha-helical structure and 10-20% beta-structures. CD band maxima at 261 and 268 nm are ascribed to transitions in the phenylalanine residues and ellipticities between 275-285 nm to the tyrosine residues. Of the four tyrosines, 3.5 are perturbed by 20% polyethylene glycol, while all of them are perturbed by 20% dimethylsulfoxide. The role of the tyrosines in the reaction with the Fc-region of immunoglobulins is discussed."}
{"id": "PMID:235434", "title": "Ion-pair formation as a source of enhanced reactivity of the essential thiol group of D-glyceraldehyde-3-phosphate dehydrogenase.", "content": "The reactivity and the mode of activation of the essential--SH group (Cys-149) of D-glyceraldehyde-3-phosphate dehydrogenase have been studied by means of a spectrophotometric method [Polg\u00e1r, L., FEBS Lett. 38, 187-190 (1974)], capable of detecting the dissociated form of the thiol group in proteins. Alkylations of Cys-149 of NAD-free D-glyceraldehyde-3-phosphate dehydrogenase with iodoacetamide and iodoacetate were investigated. The corrected absorbance change on alkylation at 250 nm (which is a direct parameter of the dissociation of the thiol group) and the alkylation rate were determined as a function of pH. The pH profiles of both dissociation and alkylation rate of Cys-149 conform to doubly sigmoid curves. All these curves implicate two ionizing groups (pK1 equals 5.5, pK2 equals 8.2). It is concluded that there are two reactive forms of the--SH group in the apoenzyme between pH 5 and 10. One reactive form corresponds to the free mercaptide ion. The other can be identified with an ion-pair composed of a mercaptide ion and some base, possibly the imidazolium group of His-176. The ion-pair has lower molar absorption coefficient and nucleophilicity than the free mercaptide ion. The two reactive forms are transformed into each other with pK2 equals 8.2. The ion-pair decomposes to a nondissociated thiol group and a protonated base with pK1 equals 5.5. In the presence of NAD, only the pH-rate profile of alkylation of D-glyceraldehyde-3-phosphate dehydrogenase was measured (at 370 nm). Using iodoacetamide as alkylating agent we also obtained a doubly sigmoid curve. A slight downward shift on pK1 and an upward shift in pK2 indicate that the ion-pair exists in a somewhat wider pH-range in the enzyme-coenzyme complex. An increase in the ionic strength of the reaction mixture from 0.09 to 0.45 M does not abolish the doubly sigmoid character of the curves determined either in the presence or in the absence of NAD.", "contents": "Ion-pair formation as a source of enhanced reactivity of the essential thiol group of D-glyceraldehyde-3-phosphate dehydrogenase. The reactivity and the mode of activation of the essential--SH group (Cys-149) of D-glyceraldehyde-3-phosphate dehydrogenase have been studied by means of a spectrophotometric method [Polg\u00e1r, L., FEBS Lett. 38, 187-190 (1974)], capable of detecting the dissociated form of the thiol group in proteins. Alkylations of Cys-149 of NAD-free D-glyceraldehyde-3-phosphate dehydrogenase with iodoacetamide and iodoacetate were investigated. The corrected absorbance change on alkylation at 250 nm (which is a direct parameter of the dissociation of the thiol group) and the alkylation rate were determined as a function of pH. The pH profiles of both dissociation and alkylation rate of Cys-149 conform to doubly sigmoid curves. All these curves implicate two ionizing groups (pK1 equals 5.5, pK2 equals 8.2). It is concluded that there are two reactive forms of the--SH group in the apoenzyme between pH 5 and 10. One reactive form corresponds to the free mercaptide ion. The other can be identified with an ion-pair composed of a mercaptide ion and some base, possibly the imidazolium group of His-176. The ion-pair has lower molar absorption coefficient and nucleophilicity than the free mercaptide ion. The two reactive forms are transformed into each other with pK2 equals 8.2. The ion-pair decomposes to a nondissociated thiol group and a protonated base with pK1 equals 5.5. In the presence of NAD, only the pH-rate profile of alkylation of D-glyceraldehyde-3-phosphate dehydrogenase was measured (at 370 nm). Using iodoacetamide as alkylating agent we also obtained a doubly sigmoid curve. A slight downward shift on pK1 and an upward shift in pK2 indicate that the ion-pair exists in a somewhat wider pH-range in the enzyme-coenzyme complex. An increase in the ionic strength of the reaction mixture from 0.09 to 0.45 M does not abolish the doubly sigmoid character of the curves determined either in the presence or in the absence of NAD."}
{"id": "PMID:235435", "title": "Etonitazine-induced rigidity and its antagonism by centrally acting muscle relaxants.", "content": "Some narcotic drugs have been reported to produce increases in muscle tone in rats. In our laboratory we have found that etonitazine produces a 'lead-pipe' rigidity of the trunk and limb musculature. The reported studies were conducted to characterize etonitazine-induced rigidity more fully, to compare the degree of rigidity with that produced by morphine, codeine and methadone, and to assess the sensitivity of this rigidity to centrally acting muscle relaxants. Of the 4 narcotics tested, etonitazine was far more potent than methadone or morphine for producing rigidity; codeine did not produce peak rigidity comparable to the other 3 narcotics. Etonitazine-induced rigidity occurs at a supraspinal level since the effect was prevented by spinal transsection. Etonitazine-induced rigidity was prevented by the narcotic antagonists cyclazocine, pentazocine and naloxone but not by the serotonin depletor, p-chlorophenylalanine. Etonitazine-induced rigidity was antagonized by centrally acting muscle relaxants, including diazepam, methocarbamol, carisoprodol and zoxazolamine; in agreement with their relative clinical muscle relaxant potencies, diazepam is the most potent antagonist of etonitazine-induced rigidity.", "contents": "Etonitazine-induced rigidity and its antagonism by centrally acting muscle relaxants. Some narcotic drugs have been reported to produce increases in muscle tone in rats. In our laboratory we have found that etonitazine produces a 'lead-pipe' rigidity of the trunk and limb musculature. The reported studies were conducted to characterize etonitazine-induced rigidity more fully, to compare the degree of rigidity with that produced by morphine, codeine and methadone, and to assess the sensitivity of this rigidity to centrally acting muscle relaxants. Of the 4 narcotics tested, etonitazine was far more potent than methadone or morphine for producing rigidity; codeine did not produce peak rigidity comparable to the other 3 narcotics. Etonitazine-induced rigidity occurs at a supraspinal level since the effect was prevented by spinal transsection. Etonitazine-induced rigidity was prevented by the narcotic antagonists cyclazocine, pentazocine and naloxone but not by the serotonin depletor, p-chlorophenylalanine. Etonitazine-induced rigidity was antagonized by centrally acting muscle relaxants, including diazepam, methocarbamol, carisoprodol and zoxazolamine; in agreement with their relative clinical muscle relaxant potencies, diazepam is the most potent antagonist of etonitazine-induced rigidity."}
{"id": "PMID:235436", "title": "Reactivity of isolated bovine mesenteric and hepatic veins to vasoactive agents and specific antigen.", "content": "In an attempt to investigate the possible contribution of the mesenteric and hepatic vasculature to the haemodynamic changes occurring during bovine systemic anaphylaxis, the pharmacological reactivity of isolated bovine mesenteric and hepatic veins was studied. Both mesenteric and hepatic veins contracted in the presence of histamine, 5-hydroxytryptamine (5HT), acetylcholine, dopamine and noradrenaline, and relaxed in the presence of isoprenaline. The mesenteric veins contracted in the presence of concentrations of isoprenaline greater than 1 mug/ml. By the use of antagonists, the receptor populations of bovine mesenteric and hepatic veins were shown to be similar to those of many other vascular preparations. Hepatic veins isolated from calves previously sensitised to horse serum contracted forcefully in the presence of horse plasma (the Schultz-Dale phenomenon), whereas mesenteric veins isolated from the same animals did not. Hepatic veins may be implicated in the haemodynamics of bovine systemic anaphylaxis.", "contents": "Reactivity of isolated bovine mesenteric and hepatic veins to vasoactive agents and specific antigen. In an attempt to investigate the possible contribution of the mesenteric and hepatic vasculature to the haemodynamic changes occurring during bovine systemic anaphylaxis, the pharmacological reactivity of isolated bovine mesenteric and hepatic veins was studied. Both mesenteric and hepatic veins contracted in the presence of histamine, 5-hydroxytryptamine (5HT), acetylcholine, dopamine and noradrenaline, and relaxed in the presence of isoprenaline. The mesenteric veins contracted in the presence of concentrations of isoprenaline greater than 1 mug/ml. By the use of antagonists, the receptor populations of bovine mesenteric and hepatic veins were shown to be similar to those of many other vascular preparations. Hepatic veins isolated from calves previously sensitised to horse serum contracted forcefully in the presence of horse plasma (the Schultz-Dale phenomenon), whereas mesenteric veins isolated from the same animals did not. Hepatic veins may be implicated in the haemodynamics of bovine systemic anaphylaxis."}
{"id": "PMID:235437", "title": "Adrenergic lipolysis in human adipose tissue in vitro.", "content": "In human adipose tissue in vitro, dose-response curves of lipolytic agents in releasing free fatty acids and glycerol into an albumine-containing medium were followed. Norepinephrine and adrenaline produced about 20% of the maximal effect of isoproterenol, isopropylnorsynephrine about 40%, theophylline more than 100%. Found pD2 values were approximately 7.4 for isoproterenol and norepinephrine, approximately 5.9 for isopropylnorsynephrine. Phentolamine (1 times 10-5 M) elevated the maximal norepinephrine effects up to the isoproterenol maxima. Phenoxybenzamine (1 times 10-5 M) had significantly lower potentiating effects. Phenylephrine depressed lipolytic actions of isoproterenol (1 times 10-6 M) showing the same pI2 value 3.0 as well in human as in rat adipose tissue and exerted per se weak lipolytic effects also. It is concluded neither potentiating actions of alpha-blockers nor depressing effects of phenylephrine in human adipose tissue seem related to affecting adrenergic alpha-receptors. The existence of antilipolytic actions of adrenergic alpha-receptors is questioned.", "contents": "Adrenergic lipolysis in human adipose tissue in vitro. In human adipose tissue in vitro, dose-response curves of lipolytic agents in releasing free fatty acids and glycerol into an albumine-containing medium were followed. Norepinephrine and adrenaline produced about 20% of the maximal effect of isoproterenol, isopropylnorsynephrine about 40%, theophylline more than 100%. Found pD2 values were approximately 7.4 for isoproterenol and norepinephrine, approximately 5.9 for isopropylnorsynephrine. Phentolamine (1 times 10-5 M) elevated the maximal norepinephrine effects up to the isoproterenol maxima. Phenoxybenzamine (1 times 10-5 M) had significantly lower potentiating effects. Phenylephrine depressed lipolytic actions of isoproterenol (1 times 10-6 M) showing the same pI2 value 3.0 as well in human as in rat adipose tissue and exerted per se weak lipolytic effects also. It is concluded neither potentiating actions of alpha-blockers nor depressing effects of phenylephrine in human adipose tissue seem related to affecting adrenergic alpha-receptors. The existence of antilipolytic actions of adrenergic alpha-receptors is questioned."}
{"id": "PMID:235439", "title": "Studies on the temperature-dependent sensitivity of mouse atria to adrenergic drugs.", "content": "The sensitivity of mouse atria (chronotropic response) to beta-adrenergic receptor antagonists was examined at 37 and 26 degrees C under various experimental conditions. When isoproterenol was used as agonist, at 37 degrees C, the pA2 value (from pA2 plots) for propranolol was 8.86 and the slope of the regression line was 0.54. At 26 degrees C, the pA2 value for propranolol was 9.2 and the slope was 0.7. In the presence of tropolone, 10-5 M, the values for pA2 and slope of the regression lines were, respectively, 9.0 and 0.90 at 37 degrees C and 9.17 and 0.98 at 26 degrees C. In other words, decreasing antagonism was prevented by low temperature and tropolone. Isoproterenol was potentiated by tropolone and low temperature, but the effects of low temperature were reduced by tropolone. With sotalol as antagonist, there was greated blockade (dose ratios) of the effects of isoproterenol at 26 than at 37 degrees C. When nylidrin, a non-catecholamine, was used as agonist there was no temperature-dependent sensitivity to sotalol. Furthermore, nylidrin was not potentiated by low temperature. The data show that the observed degree of beta-receptor antagonism can be altered by changing the bath temperature and suggest that this effect is related to COMT activity or an influence of agonist disposition in the tissue.", "contents": "Studies on the temperature-dependent sensitivity of mouse atria to adrenergic drugs. The sensitivity of mouse atria (chronotropic response) to beta-adrenergic receptor antagonists was examined at 37 and 26 degrees C under various experimental conditions. When isoproterenol was used as agonist, at 37 degrees C, the pA2 value (from pA2 plots) for propranolol was 8.86 and the slope of the regression line was 0.54. At 26 degrees C, the pA2 value for propranolol was 9.2 and the slope was 0.7. In the presence of tropolone, 10-5 M, the values for pA2 and slope of the regression lines were, respectively, 9.0 and 0.90 at 37 degrees C and 9.17 and 0.98 at 26 degrees C. In other words, decreasing antagonism was prevented by low temperature and tropolone. Isoproterenol was potentiated by tropolone and low temperature, but the effects of low temperature were reduced by tropolone. With sotalol as antagonist, there was greated blockade (dose ratios) of the effects of isoproterenol at 26 than at 37 degrees C. When nylidrin, a non-catecholamine, was used as agonist there was no temperature-dependent sensitivity to sotalol. Furthermore, nylidrin was not potentiated by low temperature. The data show that the observed degree of beta-receptor antagonism can be altered by changing the bath temperature and suggest that this effect is related to COMT activity or an influence of agonist disposition in the tissue."}
{"id": "PMID:235438", "title": "The central modulatory effect of clonidine on the cardiodepressor reflex after suppression of synthesis and storage of noradrenaline.", "content": "Rats were decerebrated and treated with a beta-adrenoceptor blocker (toliprolol, K\u00f6 592, 5 mg/kg). Increases of blood pressure were repeatedly elicited by i.v. injection of angiotensin (0.03-0. 125 mug/kg) ant eh accompanying reflex bradycardia was measured. The vagally mediated reflex bradycardia was significantly increased by clonidine, 3o mug/kg i.v., in non-pretreated animals as well as after pretreatment with reserpine (7.5 mg/kg s.c., 20 hr) and alpha-methyl-p-tyrosine-methylester (250 mg/kg i.p., 5 hr), separately or in combination. The facilitatory effect of clonidine was antagonized in all groups by i.v. injection of the alpha-adrenoceptor blocking drugs, phentolamine (5 mg/kg) and piperoxan (1 mg/kg). In the control periods before clonidine, reflex bradycardia was similar in pretreated animals to that in animals without pretreatment. It was concluded therefore that catecholamines have no essential transmitter functions in the cardiodepressor reflex loop. Therefore, the action of clonidine on cardiovascular centers in the medulla is independent of endogenous noradrenaline storage and synthesis. A direct effect is assumed on central alpha-adrenoceptors, which have a modulatory 'effector' function on the cardiodepressor reflex.", "contents": "The central modulatory effect of clonidine on the cardiodepressor reflex after suppression of synthesis and storage of noradrenaline. Rats were decerebrated and treated with a beta-adrenoceptor blocker (toliprolol, K\u00f6 592, 5 mg/kg). Increases of blood pressure were repeatedly elicited by i.v. injection of angiotensin (0.03-0. 125 mug/kg) ant eh accompanying reflex bradycardia was measured. The vagally mediated reflex bradycardia was significantly increased by clonidine, 3o mug/kg i.v., in non-pretreated animals as well as after pretreatment with reserpine (7.5 mg/kg s.c., 20 hr) and alpha-methyl-p-tyrosine-methylester (250 mg/kg i.p., 5 hr), separately or in combination. The facilitatory effect of clonidine was antagonized in all groups by i.v. injection of the alpha-adrenoceptor blocking drugs, phentolamine (5 mg/kg) and piperoxan (1 mg/kg). In the control periods before clonidine, reflex bradycardia was similar in pretreated animals to that in animals without pretreatment. It was concluded therefore that catecholamines have no essential transmitter functions in the cardiodepressor reflex loop. Therefore, the action of clonidine on cardiovascular centers in the medulla is independent of endogenous noradrenaline storage and synthesis. A direct effect is assumed on central alpha-adrenoceptors, which have a modulatory 'effector' function on the cardiodepressor reflex."}
{"id": "PMID:235474", "title": "An essential ionized acid group in sodium channels.", "content": "Several recent experiments demonstrate the presence of an essential negatively charged acid group within sodium channels. Sodium permeability titrates away at low pH as if controlled by an acid with a voltage-dependent apparent pKa in the range between 5 and 6. The alkali ion permeability sequence of the channel is best explained by interactions between the cations and a strong negative charge in the channel. Block of sodium currents by a variety of metal and organic cations again points to a cation-coordinating site in the channel. The \"blocking cations\" and protons also oppose the bindings of tetrodotoxin and saxitoxin. The negative charge in the channel seems to be essential in selecting appropriate cations and in lowering their activation energy for permeation. The same charge seems to form part of the toxin receptor. At present this charged group is the chemical group known to be associated with sodium channels.--Hille B. An essential ionized acid group in sodium channels.", "contents": "An essential ionized acid group in sodium channels. Several recent experiments demonstrate the presence of an essential negatively charged acid group within sodium channels. Sodium permeability titrates away at low pH as if controlled by an acid with a voltage-dependent apparent pKa in the range between 5 and 6. The alkali ion permeability sequence of the channel is best explained by interactions between the cations and a strong negative charge in the channel. Block of sodium currents by a variety of metal and organic cations again points to a cation-coordinating site in the channel. The \"blocking cations\" and protons also oppose the bindings of tetrodotoxin and saxitoxin. The negative charge in the channel seems to be essential in selecting appropriate cations and in lowering their activation energy for permeation. The same charge seems to form part of the toxin receptor. At present this charged group is the chemical group known to be associated with sodium channels.--Hille B. An essential ionized acid group in sodium channels."}
{"id": "PMID:235475", "title": "Non-specific decrease of cell-mediated immunity in female mice during syngeneic and allogeneic pregnancy.", "content": "Cell-mediated immunity is non-specifically reduced in the second half of H-2 incompatible pregnancy compared with syngeneic mating. Significant difference between syngeneic and allogeneic mated female mice was obtained using two independent tests: contact sensitivity to oxazolone (P smaller than 0.001) and local graft-versus-host reaction (P smaller than 0.01).", "contents": "Non-specific decrease of cell-mediated immunity in female mice during syngeneic and allogeneic pregnancy. Cell-mediated immunity is non-specifically reduced in the second half of H-2 incompatible pregnancy compared with syngeneic mating. Significant difference between syngeneic and allogeneic mated female mice was obtained using two independent tests: contact sensitivity to oxazolone (P smaller than 0.001) and local graft-versus-host reaction (P smaller than 0.01)."}
{"id": "PMID:235486", "title": "Red cell abnormalities associated with sulphasalazine maintenance therapy for ulcerative colitis.", "content": "Of 52 patients receiving a mean dose of 2.5g sulphasalazine/day as maintenance therapy for ulcerative colitis, 35 were found to have one or more drug-induced red cell abnormalities, which were not found in 50 normal controls or in 10 colitics not receiving sulphasalazine. Twenty-three of the treated patients had contracted red cells, an abnormality that is thought to result in mild haemolysis. Red cell contraction was related to the dose of sulphasalazine (P smaller than 0.01), the serum total sulphapyridine level (P smaller than 0.001), and acetylator status. Eleven of the treated patients had a macrocytosis, 21 had elevated levels of methaemoglobin, and one had Heinz bodies. A dose of 1.5 g sulphasalazine/day was not associated with red cell contraction, and is suggested as a safer maintenance dose for the asymptomatic colitic.", "contents": "Red cell abnormalities associated with sulphasalazine maintenance therapy for ulcerative colitis. Of 52 patients receiving a mean dose of 2.5g sulphasalazine/day as maintenance therapy for ulcerative colitis, 35 were found to have one or more drug-induced red cell abnormalities, which were not found in 50 normal controls or in 10 colitics not receiving sulphasalazine. Twenty-three of the treated patients had contracted red cells, an abnormality that is thought to result in mild haemolysis. Red cell contraction was related to the dose of sulphasalazine (P smaller than 0.01), the serum total sulphapyridine level (P smaller than 0.001), and acetylator status. Eleven of the treated patients had a macrocytosis, 21 had elevated levels of methaemoglobin, and one had Heinz bodies. A dose of 1.5 g sulphasalazine/day was not associated with red cell contraction, and is suggested as a safer maintenance dose for the asymptomatic colitic."}
{"id": "PMID:235487", "title": "In vitro cytotoxicity of anti-theta (Thy-1) antibodies combined with chlorambucil.", "content": "Two methods are described for linking chlorambucil to antibodies. At low pH an association is formed which is not stable under physiological conditions and the cytotoxicity is the result of the independent action of chlorambucil and antibody. At pH 8 a more stable linkage is formed and this complex shows specific toxicity for cells carrying the appropriate antigen. Uncombined chlorambucil and antibody are more cytotoxic that chlorambucil alone, especially if the cells are exposed first to the chlorambucil.", "contents": "In vitro cytotoxicity of anti-theta (Thy-1) antibodies combined with chlorambucil. Two methods are described for linking chlorambucil to antibodies. At low pH an association is formed which is not stable under physiological conditions and the cytotoxicity is the result of the independent action of chlorambucil and antibody. At pH 8 a more stable linkage is formed and this complex shows specific toxicity for cells carrying the appropriate antigen. Uncombined chlorambucil and antibody are more cytotoxic that chlorambucil alone, especially if the cells are exposed first to the chlorambucil."}
{"id": "PMID:235489", "title": "Reactions of purified hemagglutinating antigens of flaviviruses with 19S and 7S antibodies.", "content": "The rapidly sedimenting hemagglutinin (RHA) representing the purified virion and the slower-sedimenting hemagglutinin (SHA) of several flaviviruses were separated and used in hemagglutination inhibition tests with the 19S (immunoglobulin M) and 7S (immunoglobulin G) immunoglobulin fractions of rabbit antisera, prepared against purified viral antigens or against crude virus pools. The antibody specificity in tests with RHA was identical to the specificity in those employing SHA. 7S antibody cross-reacted broadly with all flavivirus antigens, whereas 19S antibodies were relatively specific in cross-reactions among flaviviruses (RHA or SHA). SHA was consistently inhibited by antibody to a greater extent than RHA. Anti-envelope protein, anti-RHA antibodies and anti-SHA antibodies were unable to discriminate between RHA and SHA. It was concluded that the relative amounts of RHA or SHA in crude hemagglutinin preparations have no influence on the result of hemagglutination inhibition tests with flaviviruses.", "contents": "Reactions of purified hemagglutinating antigens of flaviviruses with 19S and 7S antibodies. The rapidly sedimenting hemagglutinin (RHA) representing the purified virion and the slower-sedimenting hemagglutinin (SHA) of several flaviviruses were separated and used in hemagglutination inhibition tests with the 19S (immunoglobulin M) and 7S (immunoglobulin G) immunoglobulin fractions of rabbit antisera, prepared against purified viral antigens or against crude virus pools. The antibody specificity in tests with RHA was identical to the specificity in those employing SHA. 7S antibody cross-reacted broadly with all flavivirus antigens, whereas 19S antibodies were relatively specific in cross-reactions among flaviviruses (RHA or SHA). SHA was consistently inhibited by antibody to a greater extent than RHA. Anti-envelope protein, anti-RHA antibodies and anti-SHA antibodies were unable to discriminate between RHA and SHA. It was concluded that the relative amounts of RHA or SHA in crude hemagglutinin preparations have no influence on the result of hemagglutination inhibition tests with flaviviruses."}
{"id": "PMID:235488", "title": "T lymphocyte function as the principal target of lymphocytic choriomeningitis virus-induced immunosuppression.", "content": "Plaque-forming cell responses against sheep erythrocytes, Escherichia coli lipopolysaccharide, pneumococcal polysaccharide, and polyvinylpyrrolidone were examined in mice infected with lymphocytic choriomeningitis virus.  A 92 to 96 percent reduction of the thymus-dependent anti-sheep erythrocyte responses was observed 2 to 4 weeks after infection.  However, the thymus-independent responses against the three other antigens were close to normal at all stages of the infetion.  Studies on allograft immunity of infected C3H mice against DBA/2 mastocytoma cells revealed a severe suppression of the T cell-mediated cytotoxic response which was temporally related to the impaired humoral responsiveness against sheep erythrocytes.  The capacity of spleen cells from infected mice to restore immune responsiveness of lethally irradiated recipients against sheep erythrocytes was significantly reduced.  The adoptive responses, however, were clearly improved when normal thymus cells were added to the inferior spleen cells.  Moreover, it appeared that the spleen cells from immunosuppressed donor mice could not confer suppression to normal lymphoid cells.  The presented findings are consistent with the assumption that a numeric deficiency of T cells, or cells belonging to some T cell subpopulation, is the primary cause of lymphocytic choriomeningitis virus-induced immunosuppression.", "contents": "T lymphocyte function as the principal target of lymphocytic choriomeningitis virus-induced immunosuppression. Plaque-forming cell responses against sheep erythrocytes, Escherichia coli lipopolysaccharide, pneumococcal polysaccharide, and polyvinylpyrrolidone were examined in mice infected with lymphocytic choriomeningitis virus.  A 92 to 96 percent reduction of the thymus-dependent anti-sheep erythrocyte responses was observed 2 to 4 weeks after infection.  However, the thymus-independent responses against the three other antigens were close to normal at all stages of the infetion.  Studies on allograft immunity of infected C3H mice against DBA/2 mastocytoma cells revealed a severe suppression of the T cell-mediated cytotoxic response which was temporally related to the impaired humoral responsiveness against sheep erythrocytes.  The capacity of spleen cells from infected mice to restore immune responsiveness of lethally irradiated recipients against sheep erythrocytes was significantly reduced.  The adoptive responses, however, were clearly improved when normal thymus cells were added to the inferior spleen cells.  Moreover, it appeared that the spleen cells from immunosuppressed donor mice could not confer suppression to normal lymphoid cells.  The presented findings are consistent with the assumption that a numeric deficiency of T cells, or cells belonging to some T cell subpopulation, is the primary cause of lymphocytic choriomeningitis virus-induced immunosuppression."}
{"id": "PMID:235490", "title": "Reactivation of latent Herpes simplex virus after pneumococcal pneumonia in mice.", "content": "In attempts to reactivate latent herpes simplex virus, we instilled Diplococcus pneumoniae intratracheally into mice harboring latent infections in sacrosciatic spinal ganglia. All mice developed a severe pneumonia within 24 h and were given penicillin therapy. Representative mice that survived the penumonia were sacrificed at daily intervals, and appropriate tissues were examined for evidence of viral reactivation. Herpes simplex virus was reactivated in the ganglia and appeared to travel both proximally and distally in associated nerve trunks. Clinically apparent disease due to the virus was not detected in any mice.", "contents": "Reactivation of latent Herpes simplex virus after pneumococcal pneumonia in mice. In attempts to reactivate latent herpes simplex virus, we instilled Diplococcus pneumoniae intratracheally into mice harboring latent infections in sacrosciatic spinal ganglia. All mice developed a severe pneumonia within 24 h and were given penicillin therapy. Representative mice that survived the penumonia were sacrificed at daily intervals, and appropriate tissues were examined for evidence of viral reactivation. Herpes simplex virus was reactivated in the ganglia and appeared to travel both proximally and distally in associated nerve trunks. Clinically apparent disease due to the virus was not detected in any mice."}
{"id": "PMID:235491", "title": "Chemical modulation of diphtheria toxin action on cultured mammalian cells.", "content": "Ammonium chloride (4 times 10-3 M) rendered HEp-2 monolayers completely insensitive to the action of diphtheria toxin, as measured by de novo protein synthesis. Total protection was observed even with large amounts of toxin (400 minimum lethal doses/ml). Ammonium chloride did not reduce toxicity by direct action on the protein, nor did it prevent the adsorption of toxin to the cell membrane. Although the ammonium salt did not block the initial interaction between cell and toxin, it did maintain the toxin at a site amenable to neutralization with antitoxin. Surface-adsorbed toxin was inactivated by cellular enzymes or alternatively was desorbed from the membrane during a 12-h incubation in the presence of ammonium chloride. In addition, ammonium chloride provided protection to both toxin-sensitive guinea pig peritoneal macrophages and a partially toxin-resistant strain of HEp-2 cells. Sodium arsenite was effective in protecting cell monolayers from the action of diphtheria toxin; unlike ammonium chloride, its action was not dependent upon continued incubation with cells during exposure to toxin. Inhibitors of energy metabolism abolished toxin action either totally (sodium fluoride) or partially (dinitrophenol and sodium cyanide). Inhibitors of cellular proteases, on the other hand, did not modify toxin activity. The ability of several modifiers of membrane function to alter expression of toxicity for HEp-2 cells was also examined. One compound known to enhance endocytic activity, Tuftsin, had no effect, whereas poly-L-ornithine provided partial protection. Of the two compounds known to alter membrane fluidity, cytochalasin B provided partial protection for HEp-2 cell cultures, whereas colchicine had no effect. Agents that bind to sulfhydryl groups on the cell surface had no apparent effect on toxicity, suggesting that the initial toxin-cell interaction does not involve sulfhydryl groups. Those compounds that provide virtually full protection against the action of diphtheria toxic on cell monolayers (i.e., ammonium chloride, sodium fluoride, and sodium arsenite) had no inhibitory effect on the in vitro enzyme activity associated with fragment A of the toxin.", "contents": "Chemical modulation of diphtheria toxin action on cultured mammalian cells. Ammonium chloride (4 times 10-3 M) rendered HEp-2 monolayers completely insensitive to the action of diphtheria toxin, as measured by de novo protein synthesis. Total protection was observed even with large amounts of toxin (400 minimum lethal doses/ml). Ammonium chloride did not reduce toxicity by direct action on the protein, nor did it prevent the adsorption of toxin to the cell membrane. Although the ammonium salt did not block the initial interaction between cell and toxin, it did maintain the toxin at a site amenable to neutralization with antitoxin. Surface-adsorbed toxin was inactivated by cellular enzymes or alternatively was desorbed from the membrane during a 12-h incubation in the presence of ammonium chloride. In addition, ammonium chloride provided protection to both toxin-sensitive guinea pig peritoneal macrophages and a partially toxin-resistant strain of HEp-2 cells. Sodium arsenite was effective in protecting cell monolayers from the action of diphtheria toxin; unlike ammonium chloride, its action was not dependent upon continued incubation with cells during exposure to toxin. Inhibitors of energy metabolism abolished toxin action either totally (sodium fluoride) or partially (dinitrophenol and sodium cyanide). Inhibitors of cellular proteases, on the other hand, did not modify toxin activity. The ability of several modifiers of membrane function to alter expression of toxicity for HEp-2 cells was also examined. One compound known to enhance endocytic activity, Tuftsin, had no effect, whereas poly-L-ornithine provided partial protection. Of the two compounds known to alter membrane fluidity, cytochalasin B provided partial protection for HEp-2 cell cultures, whereas colchicine had no effect. Agents that bind to sulfhydryl groups on the cell surface had no apparent effect on toxicity, suggesting that the initial toxin-cell interaction does not involve sulfhydryl groups. Those compounds that provide virtually full protection against the action of diphtheria toxic on cell monolayers (i.e., ammonium chloride, sodium fluoride, and sodium arsenite) had no inhibitory effect on the in vitro enzyme activity associated with fragment A of the toxin."}
{"id": "PMID:235492", "title": "Changes in blood pH in rats after infection with Streptococcus pneumoniae.", "content": "Acid-base alterations in Streptococcus pneumoniae infection were studied in 80 male albino rats. Hematocrit and concentrations of plasma electrolytes, glucose, and total protein were also measured. At 3-h intervals throughout a 27-h study, four control and four infected rats were anesthetized with ether, and blood samples were taken. Arterial blood pH, Po2, and hematocrit increased in the infected group, whereas arterial Pco2, HCO3-, and venous Po2 decreased. Plasma K+ concentration increased slightly and glucose levels decreased in the infected rats as the sepsis progressed. No significant changes were observed in venous blood pH, HCO3-, and Pco2. Plasma Na+, Cl-, and total protein remained unchanged. The increase in arterial blood pH and decrease in arterial Pco2 and HCO3- indicated respiratory alkalosis, which was present in rats infected with S. pneumoniae.", "contents": "Changes in blood pH in rats after infection with Streptococcus pneumoniae. Acid-base alterations in Streptococcus pneumoniae infection were studied in 80 male albino rats. Hematocrit and concentrations of plasma electrolytes, glucose, and total protein were also measured. At 3-h intervals throughout a 27-h study, four control and four infected rats were anesthetized with ether, and blood samples were taken. Arterial blood pH, Po2, and hematocrit increased in the infected group, whereas arterial Pco2, HCO3-, and venous Po2 decreased. Plasma K+ concentration increased slightly and glucose levels decreased in the infected rats as the sepsis progressed. No significant changes were observed in venous blood pH, HCO3-, and Pco2. Plasma Na+, Cl-, and total protein remained unchanged. The increase in arterial blood pH and decrease in arterial Pco2 and HCO3- indicated respiratory alkalosis, which was present in rats infected with S. pneumoniae."}
{"id": "PMID:235493", "title": "Partial purification and characterization of RTG-2 fish cell interferon.", "content": "Interferon produced by rainbow trout gonadal cells (RTG-2) was partially purified. The physical, chemical, and biological properties of this in vitro produced fish cell interferon were studied. Purification was achieved by ultracentrifugation, molecular sieve gel chromatography, ion exchange chromatography, and polyacrylamide gel electrophoresis. The isoelectric point of RTG-2 interferon, as determined by CM-Sephadex (C-50) chromatography, was 7.1. Filtration through Sephadex G-150 showed that RTG-2 interferon had a molecular weight of 94,000. The partially purified material was not sedimented at 105,000 times g for 2 h at 4 C. The fish cell interferon was non-dialyzable and exhibited heat and pH stability. The partially purified material was inactivated by treatment with trypsin or 2-mercaptoethanol, but was resistant to treatment with deoxyribonuclease or ribonuclease. RTG-2 interferon which was induced by infectious pancreatic necrosis virus exhibited antiviral activity against challenge with infectious hematopoietic necrosis virus or infectious pancreatic necrosis virus. Partially purified RTG-2 interferon exhibited greater species specificity than the crude material.", "contents": "Partial purification and characterization of RTG-2 fish cell interferon. Interferon produced by rainbow trout gonadal cells (RTG-2) was partially purified. The physical, chemical, and biological properties of this in vitro produced fish cell interferon were studied. Purification was achieved by ultracentrifugation, molecular sieve gel chromatography, ion exchange chromatography, and polyacrylamide gel electrophoresis. The isoelectric point of RTG-2 interferon, as determined by CM-Sephadex (C-50) chromatography, was 7.1. Filtration through Sephadex G-150 showed that RTG-2 interferon had a molecular weight of 94,000. The partially purified material was not sedimented at 105,000 times g for 2 h at 4 C. The fish cell interferon was non-dialyzable and exhibited heat and pH stability. The partially purified material was inactivated by treatment with trypsin or 2-mercaptoethanol, but was resistant to treatment with deoxyribonuclease or ribonuclease. RTG-2 interferon which was induced by infectious pancreatic necrosis virus exhibited antiviral activity against challenge with infectious hematopoietic necrosis virus or infectious pancreatic necrosis virus. Partially purified RTG-2 interferon exhibited greater species specificity than the crude material."}
{"id": "PMID:235494", "title": "Correlation between mature and immature thymocytes. Immature thymocyte potentiating factor (IMPF) produced by mature thymocytes.", "content": "Low-dense mature thymocytes (MT) and high-dense immature thymocytes (IMT) were investigated. Immature thymocyte-potentiating factor (IMPF) was found in the supernatant from MT stimulated by Con A. On the other hand, suppressing activity was present in the supernatant from the unstimulated IMT. IMPF was different from Con A itself. Sephadex G-100 gel chromatography of IMPF revealed that the activity was recovered at the position between bovine serum albumin and ovalbumin.", "contents": "Correlation between mature and immature thymocytes. Immature thymocyte potentiating factor (IMPF) produced by mature thymocytes. Low-dense mature thymocytes (MT) and high-dense immature thymocytes (IMT) were investigated. Immature thymocyte-potentiating factor (IMPF) was found in the supernatant from MT stimulated by Con A. On the other hand, suppressing activity was present in the supernatant from the unstimulated IMT. IMPF was different from Con A itself. Sephadex G-100 gel chromatography of IMPF revealed that the activity was recovered at the position between bovine serum albumin and ovalbumin."}
{"id": "PMID:235495", "title": "Impairment of mitochondrial respiratory control by activated lymphocytes.", "content": "Mitochondria isolated from rat livers were used as a source of antigens capable of producing in vitro activation of lymphocytes that had previously been sensitized in vivo with the same antigen. Such lymphocytes were shown to have an injurious effect on target mitochondria, as was demonstrated by a new biochemical approach based on the study of the inhibition by these cells of mitochondrial respiratory control. A somewhat milder injurious capacity was also observed in normal and sensitized lymphocytes activated in vitro with the mitogen PHA. The lateration of the respiratory control of mitochondria by lymphocytes correlated with an increase in DNA synthesis in these cells.", "contents": "Impairment of mitochondrial respiratory control by activated lymphocytes. Mitochondria isolated from rat livers were used as a source of antigens capable of producing in vitro activation of lymphocytes that had previously been sensitized in vivo with the same antigen. Such lymphocytes were shown to have an injurious effect on target mitochondria, as was demonstrated by a new biochemical approach based on the study of the inhibition by these cells of mitochondrial respiratory control. A somewhat milder injurious capacity was also observed in normal and sensitized lymphocytes activated in vitro with the mitogen PHA. The lateration of the respiratory control of mitochondria by lymphocytes correlated with an increase in DNA synthesis in these cells."}
{"id": "PMID:235496", "title": "Some properties of cathepsins chemically fixed to carriers.", "content": "An insoluble preparation of rat liver cathepsin D was obtained by coupling the enzyme to Enzacryl Polyacetal (EPA-cathepsin) and to CNBr-activated Sepharose 4B. EPA-cathepsin was active toward the synthetic hexapeptides (Gly-Phe-Leu)2 and did not split hemoglobin. The optimum pH of splitting was displaced upward by 1.5 units to pH 5.0. The enzyme exhibited maximum activity at 60 degrees C. No appreciable loss of activity was seen on storage of the enzyme for 4 months or after repeated use of the preparations. Coupling of rat liver cathepsin D to activated Sepharose gave preparations active towards both protein and synthetic substrates. The preparations were totally inactive in acid media and exhibited maximum activity at pH 7.0, that is, under physiological conditions. Optimum temperature was 65 degrees. The specific activity of the preparations (pH 7.0, 65 degrees) was 60-110 percent that of the free enzyme in acid media. Proteolytic activity of the Sepharose-coupled cathepsin D was not inhibited by pepstatin, whereas that of the free enzyme was fully inhibited by this reagent. A sarcoma cathepsin, similar in some of its properties to the rat liver enzyme, was also coupled to CNBr-activated Sepharose 4B. The preparation split protein substrates at pH 7.0 and possessed enhanced thermostability. The enzymes fixed on Sepharose showed increased stability.", "contents": "Some properties of cathepsins chemically fixed to carriers. An insoluble preparation of rat liver cathepsin D was obtained by coupling the enzyme to Enzacryl Polyacetal (EPA-cathepsin) and to CNBr-activated Sepharose 4B. EPA-cathepsin was active toward the synthetic hexapeptides (Gly-Phe-Leu)2 and did not split hemoglobin. The optimum pH of splitting was displaced upward by 1.5 units to pH 5.0. The enzyme exhibited maximum activity at 60 degrees C. No appreciable loss of activity was seen on storage of the enzyme for 4 months or after repeated use of the preparations. Coupling of rat liver cathepsin D to activated Sepharose gave preparations active towards both protein and synthetic substrates. The preparations were totally inactive in acid media and exhibited maximum activity at pH 7.0, that is, under physiological conditions. Optimum temperature was 65 degrees. The specific activity of the preparations (pH 7.0, 65 degrees) was 60-110 percent that of the free enzyme in acid media. Proteolytic activity of the Sepharose-coupled cathepsin D was not inhibited by pepstatin, whereas that of the free enzyme was fully inhibited by this reagent. A sarcoma cathepsin, similar in some of its properties to the rat liver enzyme, was also coupled to CNBr-activated Sepharose 4B. The preparation split protein substrates at pH 7.0 and possessed enhanced thermostability. The enzymes fixed on Sepharose showed increased stability."}
{"id": "PMID:235497", "title": "Synthesis and charge-transfer properties of two acth analogues containing pentamethylphenylalanine in position 9.", "content": "In order to investigate the possible role of the Trp residue in ACTH as a change-transfer donor in the activation of ACTH receptors, two ACTH analogues (beta-corticotrophins (I-24) with L-Ser1 and D-Ser1, respectively) containing pentamethylphenylalanine instead of Trp have been synthesized. In these syntheses a new, alkaline-labile, amino-protecting group, the methylsulphonylethyloxycarbonyl group, was employed. The association constants of ACTH (I-24) and (Pmp9)-ACTH (I-24) with the water-soluble acceptor paraquat, were nearly equal.", "contents": "Synthesis and charge-transfer properties of two acth analogues containing pentamethylphenylalanine in position 9. In order to investigate the possible role of the Trp residue in ACTH as a change-transfer donor in the activation of ACTH receptors, two ACTH analogues (beta-corticotrophins (I-24) with L-Ser1 and D-Ser1, respectively) containing pentamethylphenylalanine instead of Trp have been synthesized. In these syntheses a new, alkaline-labile, amino-protecting group, the methylsulphonylethyloxycarbonyl group, was employed. The association constants of ACTH (I-24) and (Pmp9)-ACTH (I-24) with the water-soluble acceptor paraquat, were nearly equal."}
{"id": "PMID:235500", "title": "A study of the anticholinergic and antispasmodic activity of oxybutynin (Ditropan) on rabbit detrusor.", "content": "Experiments have been conducted which show that while the tertiary amine oxybutynin has only moderate in vitro anticholinergic and antihistaminic activity, it is a potent inhibitor of barium chloride-induced spasms of rabbit detrusor muscle. Oxybutynin exerts 1/13 the anticholinergic activity of propantheline and 1/4 that of atropine, but produces approximately 2x the inhibition of barium chloride-induced spasm than propantheline and 10x the inhibition produced by atropine. In sum, oxybutynin possesses a notable antispasmodic activity distinct from its anticholinergic activity and stronger than that of atropine, propantheline, or methantheline, which may prove useful in the treatment of smooth muscle hypermotility.", "contents": "A study of the anticholinergic and antispasmodic activity of oxybutynin (Ditropan) on rabbit detrusor. Experiments have been conducted which show that while the tertiary amine oxybutynin has only moderate in vitro anticholinergic and antihistaminic activity, it is a potent inhibitor of barium chloride-induced spasms of rabbit detrusor muscle. Oxybutynin exerts 1/13 the anticholinergic activity of propantheline and 1/4 that of atropine, but produces approximately 2x the inhibition of barium chloride-induced spasm than propantheline and 10x the inhibition produced by atropine. In sum, oxybutynin possesses a notable antispasmodic activity distinct from its anticholinergic activity and stronger than that of atropine, propantheline, or methantheline, which may prove useful in the treatment of smooth muscle hypermotility."}
{"id": "PMID:235501", "title": "Contrast media used in cystourethrography. Experimental evaluation.", "content": "The effects of five iodinated contrast media and of physiologic saline on bladder capacity were studied. It was found that a significantly greater volume of sodium chloride was tolerated than of Cysto-Conray, Conray 30. Hypaque meglumine 30, Hypaque sodium, and Dimer X. Dimer X was tolerated in the smallest volume. The reason for the difference in volume tolerated is not known. The bladder mucosa showed dehydration changes 6 hr after saline cystogram with no change at 24 hr, 48 hr, 7 days, and 3 months. The contrast media produced dehydration and hydropic and desquamative changes in the bladder mucosa with at least one of these changes persisting up to 3 months. There was no significant difference in the severity of the changes produced by the various contrast media. No evidence of inflammatory changes was seen in the bladder mucosa or wall or in the ureter with any of the agents.", "contents": "Contrast media used in cystourethrography. Experimental evaluation. The effects of five iodinated contrast media and of physiologic saline on bladder capacity were studied. It was found that a significantly greater volume of sodium chloride was tolerated than of Cysto-Conray, Conray 30. Hypaque meglumine 30, Hypaque sodium, and Dimer X. Dimer X was tolerated in the smallest volume. The reason for the difference in volume tolerated is not known. The bladder mucosa showed dehydration changes 6 hr after saline cystogram with no change at 24 hr, 48 hr, 7 days, and 3 months. The contrast media produced dehydration and hydropic and desquamative changes in the bladder mucosa with at least one of these changes persisting up to 3 months. There was no significant difference in the severity of the changes produced by the various contrast media. No evidence of inflammatory changes was seen in the bladder mucosa or wall or in the ureter with any of the agents."}
{"id": "PMID:235502", "title": "A genetical study of DDT resistance in the mosquito Aedes aegypti.", "content": "Crosses have been carried out to determine the relationship between adult DDT resistance and the three linkage groups of the mosquito Aedes aegypti. Two linkage groups were implicated in the control of DDT resistance. In the Bangkok-HR strain resistance derived mainly from linkage group III, probably with the maor effect from the gene R-DDT2. When resistance was transferred into a susceptible background, by outcrossing Bangkok-HR to strain 64 and reselecting, resistance in the resulting Bangkok-MR strain came from both linkage groups II and III.", "contents": "A genetical study of DDT resistance in the mosquito Aedes aegypti. Crosses have been carried out to determine the relationship between adult DDT resistance and the three linkage groups of the mosquito Aedes aegypti. Two linkage groups were implicated in the control of DDT resistance. In the Bangkok-HR strain resistance derived mainly from linkage group III, probably with the maor effect from the gene R-DDT2. When resistance was transferred into a susceptible background, by outcrossing Bangkok-HR to strain 64 and reselecting, resistance in the resulting Bangkok-MR strain came from both linkage groups II and III."}
{"id": "PMID:235504", "title": "Constituents of human muscle in isometric fatigue.", "content": "Three subjects performed five successive isometric contractions to fatigue; the tension in any one experiment was constant at tensions varying from 20 to 80% of the maximal voluntary contraction (MVC). The interval between contractions was held constant at 11 min. Muscle biopsy specimens were obtained at the start of the experiment, after the first, fourth, and fifth, and before the second and fifth of the successive contractions. The concentrations of ATP, CP, glycogen, and lactate were measured in each sample of muscle. Changes in ATP and glycogen were insufficient to be held accountable for the development of isometric fatigue. Changes in CP and lactate were large after fatigue at intermediate tensions, but those of CP were considered unlikely to be responsible for the fatigue. At tensions of 30-50% MVC the increase in lactate could be responsible for fatigue either directly or by indirect changes in pH; at higher and lower tensions the possibility that lactate is directly implicated in the development of fatigue seems remote.", "contents": "Constituents of human muscle in isometric fatigue. Three subjects performed five successive isometric contractions to fatigue; the tension in any one experiment was constant at tensions varying from 20 to 80% of the maximal voluntary contraction (MVC). The interval between contractions was held constant at 11 min. Muscle biopsy specimens were obtained at the start of the experiment, after the first, fourth, and fifth, and before the second and fifth of the successive contractions. The concentrations of ATP, CP, glycogen, and lactate were measured in each sample of muscle. Changes in ATP and glycogen were insufficient to be held accountable for the development of isometric fatigue. Changes in CP and lactate were large after fatigue at intermediate tensions, but those of CP were considered unlikely to be responsible for the fatigue. At tensions of 30-50% MVC the increase in lactate could be responsible for fatigue either directly or by indirect changes in pH; at higher and lower tensions the possibility that lactate is directly implicated in the development of fatigue seems remote."}
{"id": "PMID:235505", "title": "Pulmonary ventilation, blood gases, and blood pH after training of the arms or the legs.", "content": "In two groups of young healthy subjects who performed arm training (N = 5) and leg training (N = 5), respectively, the respiratory adaptation to submaximal exercise with trained and nontrained muscle groups was compared by measurement of the ventilatory equivalent (Ve/Vo2, pH, and blood gases (Pco2, Po2, and So2) in arterial blood and in venous blood from exercising extremities. After training Ve/Vo2 was significantly reduced during exercise with trained muscles, but unchanged during exercise with nontrained muscles. The reduction in Ve/Vo2 was closely related to a less pronounced increase in heart rate and in arterial lactate content, but showed no quantitative correlation to changes in arterial adaptations in trained muscles are mainly responsible for the reduction in Ve/Vo2. After training during exercise with trained as well as nontrained muscles a shift to the right of the blood oxygen dissociation curve occurred as extremities was lower while corresponding Po2 was higher.", "contents": "Pulmonary ventilation, blood gases, and blood pH after training of the arms or the legs. In two groups of young healthy subjects who performed arm training (N = 5) and leg training (N = 5), respectively, the respiratory adaptation to submaximal exercise with trained and nontrained muscle groups was compared by measurement of the ventilatory equivalent (Ve/Vo2, pH, and blood gases (Pco2, Po2, and So2) in arterial blood and in venous blood from exercising extremities. After training Ve/Vo2 was significantly reduced during exercise with trained muscles, but unchanged during exercise with nontrained muscles. The reduction in Ve/Vo2 was closely related to a less pronounced increase in heart rate and in arterial lactate content, but showed no quantitative correlation to changes in arterial adaptations in trained muscles are mainly responsible for the reduction in Ve/Vo2. After training during exercise with trained as well as nontrained muscles a shift to the right of the blood oxygen dissociation curve occurred as extremities was lower while corresponding Po2 was higher."}
{"id": "PMID:235506", "title": "Tissue oxygenation and splenic erythropoiesis during chronic hypoxia and hypercapnia.", "content": "Tissue (gas pocket) oxygen levels and erythropoietic activity were monitored in groups of rats chronically exposed to hypoxia (70 Torr PIO2), hypercapnia (60 Torr PICO2), or a combination of the two conditions. Arterial gas tensions and pH were also measured. Overall condition of the animals was assessed by comparison of growth rates with pair-fed controls. Hypoxic-hypercapnic pocket PO2 values (24-40 Torr) were similar to normoxic-normocapnic values (28-37 Torr), but greater than in hypoxia-normocapnia, and less than in normoxia-hypercapnia. Erythropoietic activity during hypoxia-hypercapnia ceased and the rats had a growth rate significantly below that of other groups. While chronic CO2 does increase tissue (pocket) oxygenation to near normal levels, probably due to increased ventilation and subsequently PaO2, the hypoxic-hypercapnic rats evidenced greater detrimental effects than did rats in hypoxic or hypercapnic environments.", "contents": "Tissue oxygenation and splenic erythropoiesis during chronic hypoxia and hypercapnia. Tissue (gas pocket) oxygen levels and erythropoietic activity were monitored in groups of rats chronically exposed to hypoxia (70 Torr PIO2), hypercapnia (60 Torr PICO2), or a combination of the two conditions. Arterial gas tensions and pH were also measured. Overall condition of the animals was assessed by comparison of growth rates with pair-fed controls. Hypoxic-hypercapnic pocket PO2 values (24-40 Torr) were similar to normoxic-normocapnic values (28-37 Torr), but greater than in hypoxia-normocapnia, and less than in normoxia-hypercapnia. Erythropoietic activity during hypoxia-hypercapnia ceased and the rats had a growth rate significantly below that of other groups. While chronic CO2 does increase tissue (pocket) oxygenation to near normal levels, probably due to increased ventilation and subsequently PaO2, the hypoxic-hypercapnic rats evidenced greater detrimental effects than did rats in hypoxic or hypercapnic environments."}
{"id": "PMID:235507", "title": "Characterization of the electron transport system in Brucella abortus.", "content": "The electron transport system in Brucella abortus has been characterized. Spectral studies of membrane preparations have indicated the presence of cytochromes a + a3 (maxima at 612 nm), cytochrome b (maxima at 560, 530, and 428 nm), cytochrome c (maxima at 552 and 522 nm), cytochrome o (maxima of carbon monoxide complex at 418 nm), and flavoproteins (minimum at 582 and 450 nm). Cytochromes a + a3 appeared only after cells had reached late log phase, possibly due to lowered oxygen tension in the medium. Dehydrogenases were shown to be present for D-erythritol 1-phosphate, L-lactate, reduced nicotinamide adenine dinucleotide, and succinate. All of the above substrates reduced the electron transport chain and at least some of the flavoproteins, indicating similar pathways of electron transport. N-ethylmaleimide, p-chloromercuribenzoate, and KCN were the only electron transport inhibitors that blocked electron transport by 100%. The system seemed to be uniquely resistant to other electron transport inhibitors.", "contents": "Characterization of the electron transport system in Brucella abortus. The electron transport system in Brucella abortus has been characterized. Spectral studies of membrane preparations have indicated the presence of cytochromes a + a3 (maxima at 612 nm), cytochrome b (maxima at 560, 530, and 428 nm), cytochrome c (maxima at 552 and 522 nm), cytochrome o (maxima of carbon monoxide complex at 418 nm), and flavoproteins (minimum at 582 and 450 nm). Cytochromes a + a3 appeared only after cells had reached late log phase, possibly due to lowered oxygen tension in the medium. Dehydrogenases were shown to be present for D-erythritol 1-phosphate, L-lactate, reduced nicotinamide adenine dinucleotide, and succinate. All of the above substrates reduced the electron transport chain and at least some of the flavoproteins, indicating similar pathways of electron transport. N-ethylmaleimide, p-chloromercuribenzoate, and KCN were the only electron transport inhibitors that blocked electron transport by 100%. The system seemed to be uniquely resistant to other electron transport inhibitors."}
{"id": "PMID:235508", "title": "Relationship between calcium and uroinic acids in the encystment of Azotobacter vinelandii.", "content": "Encystment of Azotobacter vinelandii (ATCC 12837) in modified Burk nitrogen-free medium (pH 7.0) containing 0.2 percent beta-hydroxybutyrate occurs optimally in 0.37 to 0.44 mM solutions of calcium ions. Suspension of cells in media deficient in calcium results in abortive encystment characterized by the release of viscous cyst coat material. Mature cysts rupture in ethylene glycol-bis-(beta-aminoethyl ether)-N,N'-tetraacetic acid, suggesting that calcium is a structural component of the cyst coat. Maximal stimulation of encystment by calcium ions occurs prior to the completion of the cyst exine or outer coat. The uronic acid composition of cyst components is dependent on calcium levels in the medium. Uronic acids account for 31.7 percent of the intine (inner coat) and 13 percent of the exine dry weight, and only mannuronic and guluronic acids are present in these fractions. These can be extracted as homo- and heteropolymeric sequence \"blocks\" characteristic of alginic acids. The polyuronic acid fraction of both the cyst coats contain approximately equal amounts of heteropolymeric (mannuronic acid/guluronic acid) blocks. The exine, however, is richer in polyguluronic acid and the intine is richer in polymannuronic acid. As a result, the mannuronic acid/guluronic acid ratio of the exine is lower than that of the intine. Slimes that form in abortive encystment are rich in polymannuronic acid and have a high mannuronic acid/guluronic acid ratio. A polymannuronic acid 5-epimerase is active in the mature cyst central body and the encystment culture fluid.", "contents": "Relationship between calcium and uroinic acids in the encystment of Azotobacter vinelandii. Encystment of Azotobacter vinelandii (ATCC 12837) in modified Burk nitrogen-free medium (pH 7.0) containing 0.2 percent beta-hydroxybutyrate occurs optimally in 0.37 to 0.44 mM solutions of calcium ions. Suspension of cells in media deficient in calcium results in abortive encystment characterized by the release of viscous cyst coat material. Mature cysts rupture in ethylene glycol-bis-(beta-aminoethyl ether)-N,N'-tetraacetic acid, suggesting that calcium is a structural component of the cyst coat. Maximal stimulation of encystment by calcium ions occurs prior to the completion of the cyst exine or outer coat. The uronic acid composition of cyst components is dependent on calcium levels in the medium. Uronic acids account for 31.7 percent of the intine (inner coat) and 13 percent of the exine dry weight, and only mannuronic and guluronic acids are present in these fractions. These can be extracted as homo- and heteropolymeric sequence \"blocks\" characteristic of alginic acids. The polyuronic acid fraction of both the cyst coats contain approximately equal amounts of heteropolymeric (mannuronic acid/guluronic acid) blocks. The exine, however, is richer in polyguluronic acid and the intine is richer in polymannuronic acid. As a result, the mannuronic acid/guluronic acid ratio of the exine is lower than that of the intine. Slimes that form in abortive encystment are rich in polymannuronic acid and have a high mannuronic acid/guluronic acid ratio. A polymannuronic acid 5-epimerase is active in the mature cyst central body and the encystment culture fluid."}
{"id": "PMID:235509", "title": "Psychrophilic, mesophilic, and thermophilic triosephosphate isomerases from three clostridial species.", "content": "Triosephosphate isomerase was purified to homogeneity as judged by analytical gel electrophoresis from clostridium sp. strain 69, clostridium pasteurianum, and C. thermosaccharolyticum, which grow optimally at 18, 37, and 55 C, respectively. Comparative studies on these purified proteins showed that they had the same molecular weight (53,000) and subunit molecular weight (26,500). They were equally susceptible to the active site-directed inhibitor, glycidol phosphate. However, their temperature and pH optima, as well as their stabilities to heat, urea, and sodium dodecyl sulfate, differed. The proteins also had different mobilities in acrylamide gel electrophoresis. This difference in ionic character was also reflected in the elution behavior of the enzymes from hydroxyapatite and in the isoelectric points determined by isoelectric focusing in acrylamide gel. The amino acid composition of these proteins showed that the thermophilic enzyme contains a greater amount of proline than the other enzymes. The ratio of acidic amino acids to basic amino acids was 1.79, 1.38, and 1.66 for the thermophilic mesophilic and psychrophilic enzymes, respectively. This is consistent with the relative isoelectric point values of these three enzymes.", "contents": "Psychrophilic, mesophilic, and thermophilic triosephosphate isomerases from three clostridial species. Triosephosphate isomerase was purified to homogeneity as judged by analytical gel electrophoresis from clostridium sp. strain 69, clostridium pasteurianum, and C. thermosaccharolyticum, which grow optimally at 18, 37, and 55 C, respectively. Comparative studies on these purified proteins showed that they had the same molecular weight (53,000) and subunit molecular weight (26,500). They were equally susceptible to the active site-directed inhibitor, glycidol phosphate. However, their temperature and pH optima, as well as their stabilities to heat, urea, and sodium dodecyl sulfate, differed. The proteins also had different mobilities in acrylamide gel electrophoresis. This difference in ionic character was also reflected in the elution behavior of the enzymes from hydroxyapatite and in the isoelectric points determined by isoelectric focusing in acrylamide gel. The amino acid composition of these proteins showed that the thermophilic enzyme contains a greater amount of proline than the other enzymes. The ratio of acidic amino acids to basic amino acids was 1.79, 1.38, and 1.66 for the thermophilic mesophilic and psychrophilic enzymes, respectively. This is consistent with the relative isoelectric point values of these three enzymes."}
{"id": "PMID:235510", "title": "Membrane lipoteichoic acid is not a precursor to wall teichoic acid in pneumococci.", "content": "The distribution of a pulse of teichoic acid-specific radiolabel between wall and membrane teichoic acids in pneumococci was constant over a subsequent chase period, suggesting that wall and membrane teichoic acids are biosynthesized simultaneously and independently.", "contents": "Membrane lipoteichoic acid is not a precursor to wall teichoic acid in pneumococci. The distribution of a pulse of teichoic acid-specific radiolabel between wall and membrane teichoic acids in pneumococci was constant over a subsequent chase period, suggesting that wall and membrane teichoic acids are biosynthesized simultaneously and independently."}
{"id": "PMID:235511", "title": "Growth of Pseudomonas C on C1 compounds: enzyme activites in extracts of Pseudomonas C cells grown on methanol, formaldehyde, and formate as sole carbon sources.", "content": "Pseudomonas C can grow on methanol, formaldehyde, or formate as sole carbon source. It is proposed that the assimilation of carbon by Pseudomonas C grown on different C1 growth substrates proceeds via one of two metabolic pathways, the serine pathway or the allulose pathway (the ribose phosphate cycle of formaldehyde fixation). This contention is based on the distribution of two key enzymes, each of which appears to be specifically involved in one of the assimilation pathways, glycerate dehydrogenase (serine pathway) and hexose phosphate synthetase (allulose pathway). The assimilation of methanol in Pseudomonas C cells appears to occur via the allulose pathway, whereas the utilization of formaldehyde or formate in cells grown on formaldehyde or formate as sole carbon sources appears by the serine pathway. When methanol is present together with formaldehyde or formate in the growth medium, the formaldehyde or formate is utilized by the allulose pathway.", "contents": "Growth of Pseudomonas C on C1 compounds: enzyme activites in extracts of Pseudomonas C cells grown on methanol, formaldehyde, and formate as sole carbon sources. Pseudomonas C can grow on methanol, formaldehyde, or formate as sole carbon source. It is proposed that the assimilation of carbon by Pseudomonas C grown on different C1 growth substrates proceeds via one of two metabolic pathways, the serine pathway or the allulose pathway (the ribose phosphate cycle of formaldehyde fixation). This contention is based on the distribution of two key enzymes, each of which appears to be specifically involved in one of the assimilation pathways, glycerate dehydrogenase (serine pathway) and hexose phosphate synthetase (allulose pathway). The assimilation of methanol in Pseudomonas C cells appears to occur via the allulose pathway, whereas the utilization of formaldehyde or formate in cells grown on formaldehyde or formate as sole carbon sources appears by the serine pathway. When methanol is present together with formaldehyde or formate in the growth medium, the formaldehyde or formate is utilized by the allulose pathway."}
{"id": "PMID:235512", "title": "Nanosecond spectroscopy of retinol.", "content": "Nanosecond fluorescence spectroscopy was used to study the unique binding site of the retinol-binding protein (RBP) from human serum. At pH 7.4, the binding of retinol to RBP caused the following spectroscopic changes in the ligand: (a) an enhancement of the fluorescence decay time (gamma = 8 ns); and (b) an increase in the emission anisotropy (A = 0.29). Retinol in hexane has a fluorescent decay time of 4.2 ns and a low emission anisotropy (A = 0.02). The increase in the fluorescence decay time of bound retinol is not due to dielectric relaxation effects of polar groups, since nanosecond time-resolved emission spectra of either retinol in glycerol or retinol bound to RBP, failed to show any time-dependent shifts in emission maxima during the time period investigated 0 to 30 ns. The degree of rotational mobility of bound retinol was investigated by time emission anisotropy measurements. The observed rotational correlation time (theta = 7.2 ns) is consistent with a rigid compact macromolecule of 21,000 molecular weight.", "contents": "Nanosecond spectroscopy of retinol. Nanosecond fluorescence spectroscopy was used to study the unique binding site of the retinol-binding protein (RBP) from human serum. At pH 7.4, the binding of retinol to RBP caused the following spectroscopic changes in the ligand: (a) an enhancement of the fluorescence decay time (gamma = 8 ns); and (b) an increase in the emission anisotropy (A = 0.29). Retinol in hexane has a fluorescent decay time of 4.2 ns and a low emission anisotropy (A = 0.02). The increase in the fluorescence decay time of bound retinol is not due to dielectric relaxation effects of polar groups, since nanosecond time-resolved emission spectra of either retinol in glycerol or retinol bound to RBP, failed to show any time-dependent shifts in emission maxima during the time period investigated 0 to 30 ns. The degree of rotational mobility of bound retinol was investigated by time emission anisotropy measurements. The observed rotational correlation time (theta = 7.2 ns) is consistent with a rigid compact macromolecule of 21,000 molecular weight."}
{"id": "PMID:235513", "title": "Characterization of a protein kinase and two phosphate acceptor proteins from vaccinia virions.", "content": "The phosphorylation of two purified vaccinia virus proteins (Acceptors I and II) by a protein kinase isolated from vaccinia virus cores has been studied. Phosphorylation of viral acceptor proteins by the purified enzyme was dependent on the presence of ATP, Mg2+, and protamine or other basic proteins, and was maximal at alkaline pH values. Cyclic mononucleotides did not stimulate the vaccinia protein kinase under a variety of conditions. Protamine, however, was shown to function as an enzyme activator. In its presence, the purified vaccinia protein kinase phosphorylated mainly serine residues in Acceptor I, and predominantly threonine residues in Acceptor II. Phosphorylation of protamine accounted for less than 1% of the total 23P incorporation. Tryptic peptide maps prepared from 32P-labeled Acceptors I and II demonstrated that they contained different labeled peptide sequences and were, therefore, distinct protein species. From additional studies on both purified and virus-associated protein kinase it was concluded that various proteins affected the protein kinase reaction in one of three ways. One class of proteins served as phosphate acceptors, but only when another activator protein was present. A second class consisted of proteins that were strong activators but poor phosphate acceptors. The third class contained proteins that were fair phosphate acceptors, but which also activated the phosphorylation of other acceptor proteins.", "contents": "Characterization of a protein kinase and two phosphate acceptor proteins from vaccinia virions. The phosphorylation of two purified vaccinia virus proteins (Acceptors I and II) by a protein kinase isolated from vaccinia virus cores has been studied. Phosphorylation of viral acceptor proteins by the purified enzyme was dependent on the presence of ATP, Mg2+, and protamine or other basic proteins, and was maximal at alkaline pH values. Cyclic mononucleotides did not stimulate the vaccinia protein kinase under a variety of conditions. Protamine, however, was shown to function as an enzyme activator. In its presence, the purified vaccinia protein kinase phosphorylated mainly serine residues in Acceptor I, and predominantly threonine residues in Acceptor II. Phosphorylation of protamine accounted for less than 1% of the total 23P incorporation. Tryptic peptide maps prepared from 32P-labeled Acceptors I and II demonstrated that they contained different labeled peptide sequences and were, therefore, distinct protein species. From additional studies on both purified and virus-associated protein kinase it was concluded that various proteins affected the protein kinase reaction in one of three ways. One class of proteins served as phosphate acceptors, but only when another activator protein was present. A second class consisted of proteins that were strong activators but poor phosphate acceptors. The third class contained proteins that were fair phosphate acceptors, but which also activated the phosphorylation of other acceptor proteins."}
{"id": "PMID:235514", "title": "Purification of membrane proteins from Acholeplasma laidlawii by agarose suspension electrophoresis in Tween 20 and polyacrylamide and dextran gel electrophoresis in detergent-free media.", "content": "Four of the membrane proteins from Acholeplasma laidlawii that are soluble in the nonionic detergent Tween 20 have been purified by preparative electrophoretic techniques utilizing different supporting media. The last purification step for two of the major proteins was a preparative polyacrylamide gel electrophoresis performed in the absence of any detergent. The proteins were recovered by continuous elution. The purity of the fractions was examined by analytical polyacrylamide gel electrophoresis and crossed immunoelectrophoresis. Two of the minor proteins were purified by dextran gel electrophoresis as the final step, which was also performed in a detergent-free buffer. The separation was followed by scanning the dextran gel in ultraviolet light. The proteins were recovered by slicing the gel and degrading the gel slices with dextranase. The homogeneity of the fractions was checked by electroimmunoassay.", "contents": "Purification of membrane proteins from Acholeplasma laidlawii by agarose suspension electrophoresis in Tween 20 and polyacrylamide and dextran gel electrophoresis in detergent-free media. Four of the membrane proteins from Acholeplasma laidlawii that are soluble in the nonionic detergent Tween 20 have been purified by preparative electrophoretic techniques utilizing different supporting media. The last purification step for two of the major proteins was a preparative polyacrylamide gel electrophoresis performed in the absence of any detergent. The proteins were recovered by continuous elution. The purity of the fractions was examined by analytical polyacrylamide gel electrophoresis and crossed immunoelectrophoresis. Two of the minor proteins were purified by dextran gel electrophoresis as the final step, which was also performed in a detergent-free buffer. The separation was followed by scanning the dextran gel in ultraviolet light. The proteins were recovered by slicing the gel and degrading the gel slices with dextranase. The homogeneity of the fractions was checked by electroimmunoassay."}
{"id": "PMID:235515", "title": "Effects of metals and nucleotides on the inactivation of sea urchin sperm guanylate cyclase by heat and N-ethylmaleimide.", "content": "Preincubation of sea urchin sperm guanylate cyclase at 35, 37, 40, or 43 degrees resultedin inactivation. Various metals were able to protect guanylate cyclase against heat inactivation. Estimated binary enzyme-metal dissociation constants for Mn2+, Fe2+, La3+, Ca2+, Ba2+, Mg2+, Co2+, and Ni2+ were 123, 361, 5.5, 692, 984, 335, 79, and 47 muM, respectively. Extrapolated rates of enzyme denaturation in the presence of saturating concentrations of metal divided by the rates of enzyme denaturation in the absence of metal gave values of 0.13, 0.08, minus 0.1, 0.30, 0.59, 0.66, 0.28, and 0.42 for Mn2+, Fe2+, La3+, Ca2+, Ba2+, Mg2+, Co2+, and Ni2+, respectively. GTP, MgGTP, and SrGTP protected the enzyme only slightly against heat inactivation, but CaGTP and MnGTP protected substantially. Neither CaGTP nor MnGTP protected maximally, however, unless the metal concentration exceeded that of GTP. At fixed free Mn2+ or free Ca2+ concentrations, protection curves as a function of MnGTP or CaGTP appeared to be sigmoidal, suggesting multiple nucleotide binding sites. MnATP also protected against heat, but CaATP was virtually ineffective. Sea urchin sperm guanylate cyclase was inactivated by N-ethylmaleimide; CaGTP and MnATP were effective protectants with estimated binary enzyme-Me2+ nucleoside triphosphate dissociation constants of 40 and 170 muM, respectively. MnGTP protected only slightly or not at all against N-ethylmaleimide. These results suggest that: (a) sea urchin sperm guanylate cyclase binds free metal, (b) the binding of free metal is required for protection by nucleotides, and (c) the enzyme contains multiple nucleotide binding sites.", "contents": "Effects of metals and nucleotides on the inactivation of sea urchin sperm guanylate cyclase by heat and N-ethylmaleimide. Preincubation of sea urchin sperm guanylate cyclase at 35, 37, 40, or 43 degrees resultedin inactivation. Various metals were able to protect guanylate cyclase against heat inactivation. Estimated binary enzyme-metal dissociation constants for Mn2+, Fe2+, La3+, Ca2+, Ba2+, Mg2+, Co2+, and Ni2+ were 123, 361, 5.5, 692, 984, 335, 79, and 47 muM, respectively. Extrapolated rates of enzyme denaturation in the presence of saturating concentrations of metal divided by the rates of enzyme denaturation in the absence of metal gave values of 0.13, 0.08, minus 0.1, 0.30, 0.59, 0.66, 0.28, and 0.42 for Mn2+, Fe2+, La3+, Ca2+, Ba2+, Mg2+, Co2+, and Ni2+, respectively. GTP, MgGTP, and SrGTP protected the enzyme only slightly against heat inactivation, but CaGTP and MnGTP protected substantially. Neither CaGTP nor MnGTP protected maximally, however, unless the metal concentration exceeded that of GTP. At fixed free Mn2+ or free Ca2+ concentrations, protection curves as a function of MnGTP or CaGTP appeared to be sigmoidal, suggesting multiple nucleotide binding sites. MnATP also protected against heat, but CaATP was virtually ineffective. Sea urchin sperm guanylate cyclase was inactivated by N-ethylmaleimide; CaGTP and MnATP were effective protectants with estimated binary enzyme-Me2+ nucleoside triphosphate dissociation constants of 40 and 170 muM, respectively. MnGTP protected only slightly or not at all against N-ethylmaleimide. These results suggest that: (a) sea urchin sperm guanylate cyclase binds free metal, (b) the binding of free metal is required for protection by nucleotides, and (c) the enzyme contains multiple nucleotide binding sites."}
{"id": "PMID:235516", "title": "Phosphorylation of ribosomal proteins in rat cerebral cortex in vitro.", "content": "Incubation of cerebral cortical tissue from immature rats in the presence of [32P]orthophosphate resulted in similar rates of incorporation of radioactivity into the proteins of free and membrane-bound ribosomes. Incorporation of label into ribosomal proteins of both species continued actively for at least 3 hours. Since recovery of membrane-bound ribosomes from rat cerebral cortex is quite low, further analyses of the radioactive phosphoproteins were restricted to the free ribosome population. A significant fraction of the radioactivity which was precipitated with trichloroacetic acid was not removed by heating in trichloroacetic acid at 90 degrees or extracted with organic solvents and therefore was presumed to be covalently bound to protein. The radioactive phosphoryl groups present in the ribosomal proteins were mainly in ester linkages since they were readily removed by exposure to 1 N NaOH, relatively unaltered by 1N HCl, and unaffected by hydroxylamine. This conclusion was supported by the isolation of labeled o-phosphoserine and o-phosphothreonine residues from hydrolysates of ribosomal proteins. A significant fraction of the labeled phosphoproteins in the purified ribosomes appeared to be bound tightly to the ribosome structure since only 40% of the radioactivity could be removed by extraction of these ribosomes with 1 M KCl. Phosphorylation of proteins of cerebral monoribosomes was more rapid than the same process in polyribosomes from the same source. Eight radioactive phosphoprotein bands could be detected by electrophoresis of proteins obtained from unfractionated cerebral ribosomes on unidimensional polyacrylamide gels containing sodium dodecyl sulfate. The protein nature of these materials was confirmed by pronase digestion. Proteins of subribosomal particles isolated from the total free ribosomal population were labeled differentially. When dissociation was carried out in the presence of EDTA, the small subunit contained four radioactive phosphoprotein bands, whereas the large subunit contained five. Three of the radioactive phosphoprotein components of the small subunit were removed when dissociation of cerebral ribosomes which were previously washed with high salt media was carried out in the presence of puromycin and high salt. However, only the largest labeled phosphoprotein band of the large subunit was removed by this procedure. This component exhibited the same electrophoretic mobility as one of the radioactive phosphoprotein bands which was removed from the small subunit by high salt treatment..", "contents": "Phosphorylation of ribosomal proteins in rat cerebral cortex in vitro. Incubation of cerebral cortical tissue from immature rats in the presence of [32P]orthophosphate resulted in similar rates of incorporation of radioactivity into the proteins of free and membrane-bound ribosomes. Incorporation of label into ribosomal proteins of both species continued actively for at least 3 hours. Since recovery of membrane-bound ribosomes from rat cerebral cortex is quite low, further analyses of the radioactive phosphoproteins were restricted to the free ribosome population. A significant fraction of the radioactivity which was precipitated with trichloroacetic acid was not removed by heating in trichloroacetic acid at 90 degrees or extracted with organic solvents and therefore was presumed to be covalently bound to protein. The radioactive phosphoryl groups present in the ribosomal proteins were mainly in ester linkages since they were readily removed by exposure to 1 N NaOH, relatively unaltered by 1N HCl, and unaffected by hydroxylamine. This conclusion was supported by the isolation of labeled o-phosphoserine and o-phosphothreonine residues from hydrolysates of ribosomal proteins. A significant fraction of the labeled phosphoproteins in the purified ribosomes appeared to be bound tightly to the ribosome structure since only 40% of the radioactivity could be removed by extraction of these ribosomes with 1 M KCl. Phosphorylation of proteins of cerebral monoribosomes was more rapid than the same process in polyribosomes from the same source. Eight radioactive phosphoprotein bands could be detected by electrophoresis of proteins obtained from unfractionated cerebral ribosomes on unidimensional polyacrylamide gels containing sodium dodecyl sulfate. The protein nature of these materials was confirmed by pronase digestion. Proteins of subribosomal particles isolated from the total free ribosomal population were labeled differentially. When dissociation was carried out in the presence of EDTA, the small subunit contained four radioactive phosphoprotein bands, whereas the large subunit contained five. Three of the radioactive phosphoprotein components of the small subunit were removed when dissociation of cerebral ribosomes which were previously washed with high salt media was carried out in the presence of puromycin and high salt. However, only the largest labeled phosphoprotein band of the large subunit was removed by this procedure. This component exhibited the same electrophoretic mobility as one of the radioactive phosphoprotein bands which was removed from the small subunit by high salt treatment.."}
{"id": "PMID:235517", "title": "Acid-base catalysis in the yeast alcohol dehydrogenase reaction.", "content": "The effect of pH on steady state kinetic parameters for the yeast alcohol dehydrogenase-catalyzed reduction of aldehydes and oxidation of alcohols has been studied. The oxidation of p-CH3 benzyl alcohol-1,1-h2 and -1,1-d2 by NAD+ was found to be characterized by large deuterium isotope effects (kH/kD = 4.1 plus or minus 0.1) between pH 7.5 and 9.5, indicating a rate-limiting hydride trahsfer step in this pH range; a plot of kCAT versus pH could be fit to a theoretical titration curve, pK = 8.25, where kCAT increases with increasing pH. The Michaelis constnat for p-CH3 benzyl alcohol was independent of pH. The reduction of p-CH3 benzaldehyde by NADH and reduced nicotinamide adenine dinucleotide with deuterium in the 4-A position (NADD) cound not be studied below pH 8.5 due to substrate inhibition; however, between pH 8.5 and 9.5, kCAT was found to decrease with increasing pH and to be characterized by significant isotope effects (kH/kD = 3.3 plus or minus 0.3). In the case of acetaldehyde reduction by NADH and NADD, isotope effects were found to be small and exxentially invariant (kH/kD = 2.O plus or minus 0.4) between pH 7.2 and 9.5, suggesting a partially rate-limiting hydride transger step for this substrate; a plot of kCAT/K'b (where K'b is the Michaelis constant for acetaldehyde) versus pH could be fit to a titration curve, pK = 8.25. The titration curve for acetaldehyde reduction has the same pK but is opposite in direction to that observed for p-CH3 benzyl alcohol oxidation. The data presented in this paper indicate a dependence on different enzyme forms for aldehyde reduction and alcohol oxidation and are consistent with a single active site side chain, pK = 8.25, which functions in acid-base catalysis of the hydride transfer step.", "contents": "Acid-base catalysis in the yeast alcohol dehydrogenase reaction. The effect of pH on steady state kinetic parameters for the yeast alcohol dehydrogenase-catalyzed reduction of aldehydes and oxidation of alcohols has been studied. The oxidation of p-CH3 benzyl alcohol-1,1-h2 and -1,1-d2 by NAD+ was found to be characterized by large deuterium isotope effects (kH/kD = 4.1 plus or minus 0.1) between pH 7.5 and 9.5, indicating a rate-limiting hydride trahsfer step in this pH range; a plot of kCAT versus pH could be fit to a theoretical titration curve, pK = 8.25, where kCAT increases with increasing pH. The Michaelis constnat for p-CH3 benzyl alcohol was independent of pH. The reduction of p-CH3 benzaldehyde by NADH and reduced nicotinamide adenine dinucleotide with deuterium in the 4-A position (NADD) cound not be studied below pH 8.5 due to substrate inhibition; however, between pH 8.5 and 9.5, kCAT was found to decrease with increasing pH and to be characterized by significant isotope effects (kH/kD = 3.3 plus or minus 0.3). In the case of acetaldehyde reduction by NADH and NADD, isotope effects were found to be small and exxentially invariant (kH/kD = 2.O plus or minus 0.4) between pH 7.2 and 9.5, suggesting a partially rate-limiting hydride transger step for this substrate; a plot of kCAT/K'b (where K'b is the Michaelis constant for acetaldehyde) versus pH could be fit to a titration curve, pK = 8.25. The titration curve for acetaldehyde reduction has the same pK but is opposite in direction to that observed for p-CH3 benzyl alcohol oxidation. The data presented in this paper indicate a dependence on different enzyme forms for aldehyde reduction and alcohol oxidation and are consistent with a single active site side chain, pK = 8.25, which functions in acid-base catalysis of the hydride transfer step."}
{"id": "PMID:235518", "title": "Influence of adenine nucleotides on the inhibition of photophosphorylation in spinach chloroplasts by N-ethylmaleimide.", "content": "The incubation of spinach chloroplasts with 1 mM N-ethylmaleimide in light for 60 to 90 s results in a partial, irreversible inhibition of photophosphorylation. The inhibition was not overcome at infinite light intensity or at infinite concentrations of the phosphorylation substrates. Although the inhibition diminished with decreasing concentrations of adenosine diphosphate in the assay of phosphorylation, the inhibition of guanosine diphosphate phosphorylation was independent of the concentration of this nucleotide. Although adenosine di- or triphosphate (10 to 30 muM) alone partially prevented the development of the N-ethylmaleimide inhibition of phosphorylation, these nucleotides were more effective when either 1 mM inorganic phosphate or arsenate was also present. The light-dependent incorporation of N-ethylmaleimide into chloroplast-bound coupling factor 1 was affected by adenosine triphosphate and inorganic phosphate in a manner similar to the onset of N-ethylmaleimide inhibition. Since guanosine diphosphate did not protect phosphorylation from N-ethylmaleimide inhibition but is phosphorylated at rapid rates, it is apparent that coupling factor 1 in chloroplasts has multiple nucleotide recognition sites.", "contents": "Influence of adenine nucleotides on the inhibition of photophosphorylation in spinach chloroplasts by N-ethylmaleimide. The incubation of spinach chloroplasts with 1 mM N-ethylmaleimide in light for 60 to 90 s results in a partial, irreversible inhibition of photophosphorylation. The inhibition was not overcome at infinite light intensity or at infinite concentrations of the phosphorylation substrates. Although the inhibition diminished with decreasing concentrations of adenosine diphosphate in the assay of phosphorylation, the inhibition of guanosine diphosphate phosphorylation was independent of the concentration of this nucleotide. Although adenosine di- or triphosphate (10 to 30 muM) alone partially prevented the development of the N-ethylmaleimide inhibition of phosphorylation, these nucleotides were more effective when either 1 mM inorganic phosphate or arsenate was also present. The light-dependent incorporation of N-ethylmaleimide into chloroplast-bound coupling factor 1 was affected by adenosine triphosphate and inorganic phosphate in a manner similar to the onset of N-ethylmaleimide inhibition. Since guanosine diphosphate did not protect phosphorylation from N-ethylmaleimide inhibition but is phosphorylated at rapid rates, it is apparent that coupling factor 1 in chloroplasts has multiple nucleotide recognition sites."}
{"id": "PMID:235519", "title": "Formation and excretion of pyrrole-2-carboxylic acid. Whole animal and enzyme studies in the rat.", "content": "A corrected method for the measurement of pyrrole-2-carboxylate in rat urine was used in studies of its excretion under various experimental conditions. The findings implicated administered hydroxy-L-proline as a relatively efficient source of urinary pyrrole-2-carboxylate and tended to exclude administered L-proline as a significant direct source. Removal of aerobic gut flora had no influence on the excretion of pyrrole-2-carboxylate either endogenously or following hydroxy-L-proline administration. Related studied showed that rat kidney L-amino acid oxidase catalyzes oxidation of hydroxy-L-proline to delta1-pyrroline-4-hydroxy-2-carboxylate, which is converted to pyrrole-2-carboxylate on acidification of reaction mixtures. All findings were consistent with hydroxy-L-proline as the source of endogenous pyrrole-2-carboxylate excretion. Excretion patterns and labeling patterns were compared after administration of pyrrole-2-carboxylate or of hydroxy-proline epimers. From these data, the true excretion product of hydroxy-L-proline oxidation by L-amino acid oxidase appeared to be the unstable oxidation product, delta1-pyrroline-4-hydroxy-2-carboxylate, which is converted to pyrrole-2-carboxylate in urine. The capacity of homogenates of guinea pig kidney and human kidney to carry out oxidation of hydroxy-L-proline to pyrrole-2-carboxylate was much less than that of rat kidney, consistent with the lower levels of urinary pyrrole-2-carboxylate in these species. Experiments designed to examine the modest increase of pyrrole-2-carboxylate excretion after proline loads led to new observations on tissue levels of hydroxy-L-proline following proline administration and on the inhibition by L-proline of hydroxy-L-proline oxidase.", "contents": "Formation and excretion of pyrrole-2-carboxylic acid. Whole animal and enzyme studies in the rat. A corrected method for the measurement of pyrrole-2-carboxylate in rat urine was used in studies of its excretion under various experimental conditions. The findings implicated administered hydroxy-L-proline as a relatively efficient source of urinary pyrrole-2-carboxylate and tended to exclude administered L-proline as a significant direct source. Removal of aerobic gut flora had no influence on the excretion of pyrrole-2-carboxylate either endogenously or following hydroxy-L-proline administration. Related studied showed that rat kidney L-amino acid oxidase catalyzes oxidation of hydroxy-L-proline to delta1-pyrroline-4-hydroxy-2-carboxylate, which is converted to pyrrole-2-carboxylate on acidification of reaction mixtures. All findings were consistent with hydroxy-L-proline as the source of endogenous pyrrole-2-carboxylate excretion. Excretion patterns and labeling patterns were compared after administration of pyrrole-2-carboxylate or of hydroxy-proline epimers. From these data, the true excretion product of hydroxy-L-proline oxidation by L-amino acid oxidase appeared to be the unstable oxidation product, delta1-pyrroline-4-hydroxy-2-carboxylate, which is converted to pyrrole-2-carboxylate in urine. The capacity of homogenates of guinea pig kidney and human kidney to carry out oxidation of hydroxy-L-proline to pyrrole-2-carboxylate was much less than that of rat kidney, consistent with the lower levels of urinary pyrrole-2-carboxylate in these species. Experiments designed to examine the modest increase of pyrrole-2-carboxylate excretion after proline loads led to new observations on tissue levels of hydroxy-L-proline following proline administration and on the inhibition by L-proline of hydroxy-L-proline oxidase."}
{"id": "PMID:235520", "title": "Xanthosine-5'-phosphate amidotransferase from Escherichia coli.", "content": "The purified enzyme xanthosine-5'-monophosphate (XMP) aminase from Escherichia coli strain B-96 is shown to possess catalytic activity with either glutamine or ammonia as a substrate. This enzyme, which possesses identical subunits, has the following properties: (a) a pH optimum of 8.3 for both aminase and amidotransferase; (b) an apparent K-m for both glutamine and NH3 of 1 mM; (c) an amidotransferase that is approximately 2 times more active than the aminase; (d) a linear relationship between velocity and enzyme concentrationfor both activities; (e) inhibition of both activities by the glutamine analogue 6-diazo-5-oxo-L-norleucine, but the amidotransferase is more sensitive than the aminase; and (f) inhbiition of both activities by the adenosine analogue, psicofuranine, but again the amidotransferase activity is more sensitive than the aminase. The so-called XMP aminase from the E. coli mutant B-24-1 also has been examined in both crude extracts nad ammonium sulfate fractions and the following data have been obtained: (a) both preparations of enzyme contain aminase and amidotransferase activity; (b) both activities have the same substrate requirements; (c) the pH optima for both activities in the crude extract are identical with those found with the purified enzyme preparation; and (d) the amidotransferase activity in the crude extract and the ammonium sulfate fractions is 2- to 3-fold more active than the aminase. These data demonstrate that this enzyme from E. coli is not strictly a XMP aminase but is, in fact, an amidotransferase capable of utilizing either glutamine or NH3 as a substrate.", "contents": "Xanthosine-5'-phosphate amidotransferase from Escherichia coli. The purified enzyme xanthosine-5'-monophosphate (XMP) aminase from Escherichia coli strain B-96 is shown to possess catalytic activity with either glutamine or ammonia as a substrate. This enzyme, which possesses identical subunits, has the following properties: (a) a pH optimum of 8.3 for both aminase and amidotransferase; (b) an apparent K-m for both glutamine and NH3 of 1 mM; (c) an amidotransferase that is approximately 2 times more active than the aminase; (d) a linear relationship between velocity and enzyme concentrationfor both activities; (e) inhibition of both activities by the glutamine analogue 6-diazo-5-oxo-L-norleucine, but the amidotransferase is more sensitive than the aminase; and (f) inhbiition of both activities by the adenosine analogue, psicofuranine, but again the amidotransferase activity is more sensitive than the aminase. The so-called XMP aminase from the E. coli mutant B-24-1 also has been examined in both crude extracts nad ammonium sulfate fractions and the following data have been obtained: (a) both preparations of enzyme contain aminase and amidotransferase activity; (b) both activities have the same substrate requirements; (c) the pH optima for both activities in the crude extract are identical with those found with the purified enzyme preparation; and (d) the amidotransferase activity in the crude extract and the ammonium sulfate fractions is 2- to 3-fold more active than the aminase. These data demonstrate that this enzyme from E. coli is not strictly a XMP aminase but is, in fact, an amidotransferase capable of utilizing either glutamine or NH3 as a substrate."}
{"id": "PMID:235521", "title": "Magnetic resonance study of exchangeable protons in human carbonic anhydrases.", "content": "A titratable exchangeable proton resonance assignable to a histidine imidazole ring N--H proton is observed approximately minus 15 ppm downfield from tetramethylsilane. The chemical shift of this resonance is affected by sulfonamide and anion inhibitors, and by removal of zinc or replacement of zinc by cobalt, indicating that the proton is located at or near the active site. The pH dependence of the chemical shift of this resonance, which is abolished by inhibitors, reflects the titration of a group with a pK-a of 7.3 in human carbonic anhydrase B and smaller than or equal to 7.1 in human carbonic anhydrase C. These pK-a values are interpreted to be due to the ionization of a neutral imidazole to form the imidazolate anion coordinated to zinc. A mechanism for enzymatic catalysis involving reversible deprotonation and coordination of a histidine to the metal is consistent with these studies.", "contents": "Magnetic resonance study of exchangeable protons in human carbonic anhydrases. A titratable exchangeable proton resonance assignable to a histidine imidazole ring N--H proton is observed approximately minus 15 ppm downfield from tetramethylsilane. The chemical shift of this resonance is affected by sulfonamide and anion inhibitors, and by removal of zinc or replacement of zinc by cobalt, indicating that the proton is located at or near the active site. The pH dependence of the chemical shift of this resonance, which is abolished by inhibitors, reflects the titration of a group with a pK-a of 7.3 in human carbonic anhydrase B and smaller than or equal to 7.1 in human carbonic anhydrase C. These pK-a values are interpreted to be due to the ionization of a neutral imidazole to form the imidazolate anion coordinated to zinc. A mechanism for enzymatic catalysis involving reversible deprotonation and coordination of a histidine to the metal is consistent with these studies."}
{"id": "PMID:235522", "title": "Conversion of pepsinogen to pepsin. Further evidence for intramolecular and pepsin-catalyzed activation.", "content": "Exposure of pepsinogen to acid for less than 2 min yields a product with proteolytic activity. This activity is due to intramolecular and intermolecular formation of pepsin from pepsinogen. We find no evidence for intermolecular proteolytic activity in the zymogen. These conclusions are based upon two sets of experiments. First, chemical cleavage of pepsinogen during short activation is demonstrated by quantitative analysis of the NH2-terminal 2 residues of the pepsin and pepsinogen in an activation mixture. In addition, quantitative NH2-terminal analyses after activation under different conditions confirm our previous inference that the product of unimolecular pepsinogen activation is homogeneous whereas bimolecular activation produces a pepsin product with a variety of NH2 termini. Second, spectral changes which occur upon acidification of a pepsinogen solution and are reversed by neutralization are shown to be consistent with the chemical cleavage of pepsinogen during acidification. The first order rate constant for pepsinogen activation, calculated from these spectral experiments, agrees well with the value we had determined previously.", "contents": "Conversion of pepsinogen to pepsin. Further evidence for intramolecular and pepsin-catalyzed activation. Exposure of pepsinogen to acid for less than 2 min yields a product with proteolytic activity. This activity is due to intramolecular and intermolecular formation of pepsin from pepsinogen. We find no evidence for intermolecular proteolytic activity in the zymogen. These conclusions are based upon two sets of experiments. First, chemical cleavage of pepsinogen during short activation is demonstrated by quantitative analysis of the NH2-terminal 2 residues of the pepsin and pepsinogen in an activation mixture. In addition, quantitative NH2-terminal analyses after activation under different conditions confirm our previous inference that the product of unimolecular pepsinogen activation is homogeneous whereas bimolecular activation produces a pepsin product with a variety of NH2 termini. Second, spectral changes which occur upon acidification of a pepsinogen solution and are reversed by neutralization are shown to be consistent with the chemical cleavage of pepsinogen during acidification. The first order rate constant for pepsinogen activation, calculated from these spectral experiments, agrees well with the value we had determined previously."}
{"id": "PMID:235523", "title": "Phosphorylation of a 22,000-dalton component of the cardiac sarcoplasmic reticulum by adenosine 3':5'-monophosphate-dependent protein kinase.", "content": "Cardiac microsomes were incubated with [gamma-32P]ATP and a cardiac adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase in the presence of ethylene glycol bis(bets-aminoethyl ether)-N,N'-tetraacetic acid. After solubilization in sodium dodecyl sulfate and fractionation by polyacrylamide gel electrophoresis, a single microsomal protein component of approximately 22,000 daltons was found to bind most of the 32P label. The 32P labeling of this component increased several fold when NaF was included in the incubation medium. No other component of cardiac microsomes, including sarcoplasmic reticulum ATPase protein, contained significant amounts of 32P label. This 22,000-dalton phosphoprotein formed by cyclic AMP-dependent protein kinase had stability characteristics of a phosphoester rather than an acyl phosphate. Washing of microsomes with buffered KCl did not decrease the amount of 32P labeling to the 22,000-dalton protein, suggesting that this protein is associated with the membranes of sarcoplasmic reticulum rather than being a contaminant from other soluble proteins. The 22,000-dalton protein was susceptible to trypsin. Brief digestion with trypsin in the presence of 1 M sucrose did not significantly affect microsomal calcium transport activity, but prevented both subsequent phosphorylation of the 22,000-dalton protein and stimulation of calcium uptake by cyclic AMP-dependent protein kinase, suggesting that this protein is a modulator of the calcium pump. These results are consistent with previous findings (Kirchberger, M.A., Tada, M., and Katz, A.M. (1974) J. Biol. Chem. 249, 6166-6173; Tada, M., Kirchberger, M.A., Repke, D.I., and Katz, A.M. (1974) J. Biol. Chem. 249, 6174-6180) that cyclic AMP-dependent protein kinase-catalyzed phosphorylation is associated with stimulation of calcium transport in the cardiac sarcoplasmic reticulum, and further indicate that this phosphorylation occurs at a component of low mass (22,000 daltons) of the cardiac sarcoplasmic reticulum which, while separable from the calcium transport ATPase protein (100,000 daltons) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, has the ability to regulate calcium transport by the cardiac sarcoplasmic reticulum.", "contents": "Phosphorylation of a 22,000-dalton component of the cardiac sarcoplasmic reticulum by adenosine 3':5'-monophosphate-dependent protein kinase. Cardiac microsomes were incubated with [gamma-32P]ATP and a cardiac adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase in the presence of ethylene glycol bis(bets-aminoethyl ether)-N,N'-tetraacetic acid. After solubilization in sodium dodecyl sulfate and fractionation by polyacrylamide gel electrophoresis, a single microsomal protein component of approximately 22,000 daltons was found to bind most of the 32P label. The 32P labeling of this component increased several fold when NaF was included in the incubation medium. No other component of cardiac microsomes, including sarcoplasmic reticulum ATPase protein, contained significant amounts of 32P label. This 22,000-dalton phosphoprotein formed by cyclic AMP-dependent protein kinase had stability characteristics of a phosphoester rather than an acyl phosphate. Washing of microsomes with buffered KCl did not decrease the amount of 32P labeling to the 22,000-dalton protein, suggesting that this protein is associated with the membranes of sarcoplasmic reticulum rather than being a contaminant from other soluble proteins. The 22,000-dalton protein was susceptible to trypsin. Brief digestion with trypsin in the presence of 1 M sucrose did not significantly affect microsomal calcium transport activity, but prevented both subsequent phosphorylation of the 22,000-dalton protein and stimulation of calcium uptake by cyclic AMP-dependent protein kinase, suggesting that this protein is a modulator of the calcium pump. These results are consistent with previous findings (Kirchberger, M.A., Tada, M., and Katz, A.M. (1974) J. Biol. Chem. 249, 6166-6173; Tada, M., Kirchberger, M.A., Repke, D.I., and Katz, A.M. (1974) J. Biol. Chem. 249, 6174-6180) that cyclic AMP-dependent protein kinase-catalyzed phosphorylation is associated with stimulation of calcium transport in the cardiac sarcoplasmic reticulum, and further indicate that this phosphorylation occurs at a component of low mass (22,000 daltons) of the cardiac sarcoplasmic reticulum which, while separable from the calcium transport ATPase protein (100,000 daltons) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, has the ability to regulate calcium transport by the cardiac sarcoplasmic reticulum."}
{"id": "PMID:235524", "title": "Membrane-bound neuraminidases of rat liver. Neuraminidase activity in Golgi apparatus.", "content": "The bulk (60 to 65%) of the neuraminidase activity present in rat liver homogenates was found in the M + L (mitochondria plus lysosomes) fraction, The patterns of subcellular distribution were essentially identical whether disialogangliosides or neuramin-lactose (2 yields 3') were utilized as substrates. A new neuraminidase, which hydrolyzes sialyl trisaccharides but which does not act upon glycoproteins and gangliosides, was detected in Golgi apparatus. Unlike the other particulate neuraminidases of rat liver, the Golgi enzyme is stimulated by prior incubation and by the addition of Ca2+ or Zn2+ at 1 mM concentration. Although plasma membrane-rich fractions are often contaminated by Golgi membranes the marked differences in their enzymic properties allowed a clear distinction between the neuraminidases present in these two types of membranes.", "contents": "Membrane-bound neuraminidases of rat liver. Neuraminidase activity in Golgi apparatus. The bulk (60 to 65%) of the neuraminidase activity present in rat liver homogenates was found in the M + L (mitochondria plus lysosomes) fraction, The patterns of subcellular distribution were essentially identical whether disialogangliosides or neuramin-lactose (2 yields 3') were utilized as substrates. A new neuraminidase, which hydrolyzes sialyl trisaccharides but which does not act upon glycoproteins and gangliosides, was detected in Golgi apparatus. Unlike the other particulate neuraminidases of rat liver, the Golgi enzyme is stimulated by prior incubation and by the addition of Ca2+ or Zn2+ at 1 mM concentration. Although plasma membrane-rich fractions are often contaminated by Golgi membranes the marked differences in their enzymic properties allowed a clear distinction between the neuraminidases present in these two types of membranes."}
{"id": "PMID:235525", "title": "Solvent-temperature perturbations of ionizable groups as a tool for the investigation of the active site of enzymes.", "content": "Co-solvent and temperature effects on the pK of histidine (imidazolium) residue 46 of trypsin, as well as of weak electrolytes (buffers), which have been reported in two preceding papers, can be satisfactorily explained in terms of enthalpy-entropy compensation patterns. Such patterns have been generated for various mixed solvents between 20 degrees and minus 20 degrees and minus 50 degrees. Under these conditions compensation temperature, T-c, is strongly dependent on the nature of the ionizable group studied: 240 plus or minus 10 K for neutral acids and 310 plus or minus 5 K for cationic acids. This work focuses on the possibilities offered and on the problems raised by the use of this methodology as a tool in the investigation of the active site of enzymes. Furthermore, it is shown in the case of histidine residue 46 of trypsin that the co-solvent effect vanishes at the compensation temperature, a result of great practical significance if applicable to any ionizable group at the active site of enzymes.", "contents": "Solvent-temperature perturbations of ionizable groups as a tool for the investigation of the active site of enzymes. Co-solvent and temperature effects on the pK of histidine (imidazolium) residue 46 of trypsin, as well as of weak electrolytes (buffers), which have been reported in two preceding papers, can be satisfactorily explained in terms of enthalpy-entropy compensation patterns. Such patterns have been generated for various mixed solvents between 20 degrees and minus 20 degrees and minus 50 degrees. Under these conditions compensation temperature, T-c, is strongly dependent on the nature of the ionizable group studied: 240 plus or minus 10 K for neutral acids and 310 plus or minus 5 K for cationic acids. This work focuses on the possibilities offered and on the problems raised by the use of this methodology as a tool in the investigation of the active site of enzymes. Furthermore, it is shown in the case of histidine residue 46 of trypsin that the co-solvent effect vanishes at the compensation temperature, a result of great practical significance if applicable to any ionizable group at the active site of enzymes."}
{"id": "PMID:235526", "title": "Fatty acid synthetase. A steady state kinetic analysis of the reaction catalyzed by the enzyme from pigeon liver.", "content": "The kinetic mechanism of pigeon liver fatty acid synthetase action has been studied using steady state kinetic analysis. Initial velocity studies are consistent with an earlier suggestion that the enzyme catalyzes this reaction by a seven-site ping-pong mechanism. Although the range of substrate concentrations that could be used was limited by several factors, the initial velocity patterns showing the relationship between the substrates acetyl coenzyme CoA, malonyl-CoA, and NADPH appear to be a series of parallel lines, regardless of which substrate is varied at fixed levels of a second substrate. However, two of the substrates, acetyl-CoA and malonly-CoA, apparently exhibit a competitive substrate inhibition with respect to each other, but NADPH shows no inhibition of any kind. Product inhibition patterns suggest that free CoA is competitive versus acetyl-CoA and malonyl-CoA and is uncompetitive versus NADPH, and that NADP+ is competitive versus NADPH and uncompetitive versus acetyl-CoA or malonyl-CoA. These results are consistent with a seven-site ping-pong mechanism with intermediates covalently bound to 4'-phosphopantetheine (part of acyl carrier protein). Double competitive substrate inhibition by acetyl-CoA and malonyl-CoA is consistent with the rate equation derived for the over-all mechanism. The kinetic mechanism developed from these results is capable of explaining the formation of fatty acids from malonyl-CoA and NADPH alone (Katiyar, S. S., Briedis, A. V., and Porter, J. W. (1974) Arch. Biochem. Biophys. 162, 412-420) and also the formation of triacetic acid lactone from either malonyl-CoA alone or acetyl-CoA plus malonyl-CoA.", "contents": "Fatty acid synthetase. A steady state kinetic analysis of the reaction catalyzed by the enzyme from pigeon liver. The kinetic mechanism of pigeon liver fatty acid synthetase action has been studied using steady state kinetic analysis. Initial velocity studies are consistent with an earlier suggestion that the enzyme catalyzes this reaction by a seven-site ping-pong mechanism. Although the range of substrate concentrations that could be used was limited by several factors, the initial velocity patterns showing the relationship between the substrates acetyl coenzyme CoA, malonyl-CoA, and NADPH appear to be a series of parallel lines, regardless of which substrate is varied at fixed levels of a second substrate. However, two of the substrates, acetyl-CoA and malonly-CoA, apparently exhibit a competitive substrate inhibition with respect to each other, but NADPH shows no inhibition of any kind. Product inhibition patterns suggest that free CoA is competitive versus acetyl-CoA and malonyl-CoA and is uncompetitive versus NADPH, and that NADP+ is competitive versus NADPH and uncompetitive versus acetyl-CoA or malonyl-CoA. These results are consistent with a seven-site ping-pong mechanism with intermediates covalently bound to 4'-phosphopantetheine (part of acyl carrier protein). Double competitive substrate inhibition by acetyl-CoA and malonyl-CoA is consistent with the rate equation derived for the over-all mechanism. The kinetic mechanism developed from these results is capable of explaining the formation of fatty acids from malonyl-CoA and NADPH alone (Katiyar, S. S., Briedis, A. V., and Porter, J. W. (1974) Arch. Biochem. Biophys. 162, 412-420) and also the formation of triacetic acid lactone from either malonyl-CoA alone or acetyl-CoA plus malonyl-CoA."}
{"id": "PMID:235527", "title": "Spectral studies of conformational changes induced in beta-glucuronidase by saccharo-1,4-lactone.", "content": "Ultraviolet difference spectroscopy has been used to study the binding of the transition state analog saccharo-1,4-lactone to purified rat preputial gland beta-glucuronidase. At pH 4.5 (the pH optimum), the inhibitor induces a difference spectrum indicative of a change in the environment of tryptophyl residues. Based on the magnitude of the induced difference spectrum as a quantitative measure of inhibitor binding, a titration curve for saccharo-1,4-lactone was obtained. A Scatchard plot of the titration data indicates that 4 molecules of inhibitor bind to the enzyme tetramer at a K-I of 4 times 10-7 M. The inhibitor also induces a similar difference spectrum at pH 7.5, although the binding is considerably weaker at this pH than at pH 4.5. When the native enzyme at pH 4.5 is compared with the native enzyme at pH 7.5, a difference spectrum, distinct from that of the binding of saccharo-1,4-lactone, is observed, indicating that the enzyme exists in different conformations at these pH values. The indication that tryptophyl residues are perturbed upon binding of saccharo-1,4-lactone was supported by studies carried out with N-bromosuccinimide. At pH 4.3, this reagent was found to oxidize 6 tryptophyl residues in the native enzyme but only three in the saccharo-1,4-lactone-inhibited enzyme. A spectrophotometric titration of the enzyme indicated that of the 33 tyrosyl residues per subunit, only 5 to 6 ionize at the pK expected for free phenolic groups.", "contents": "Spectral studies of conformational changes induced in beta-glucuronidase by saccharo-1,4-lactone. Ultraviolet difference spectroscopy has been used to study the binding of the transition state analog saccharo-1,4-lactone to purified rat preputial gland beta-glucuronidase. At pH 4.5 (the pH optimum), the inhibitor induces a difference spectrum indicative of a change in the environment of tryptophyl residues. Based on the magnitude of the induced difference spectrum as a quantitative measure of inhibitor binding, a titration curve for saccharo-1,4-lactone was obtained. A Scatchard plot of the titration data indicates that 4 molecules of inhibitor bind to the enzyme tetramer at a K-I of 4 times 10-7 M. The inhibitor also induces a similar difference spectrum at pH 7.5, although the binding is considerably weaker at this pH than at pH 4.5. When the native enzyme at pH 4.5 is compared with the native enzyme at pH 7.5, a difference spectrum, distinct from that of the binding of saccharo-1,4-lactone, is observed, indicating that the enzyme exists in different conformations at these pH values. The indication that tryptophyl residues are perturbed upon binding of saccharo-1,4-lactone was supported by studies carried out with N-bromosuccinimide. At pH 4.3, this reagent was found to oxidize 6 tryptophyl residues in the native enzyme but only three in the saccharo-1,4-lactone-inhibited enzyme. A spectrophotometric titration of the enzyme indicated that of the 33 tyrosyl residues per subunit, only 5 to 6 ionize at the pK expected for free phenolic groups."}
{"id": "PMID:235528", "title": "Thioredoxin reductase-mediated hydrogen transfer from Escherichia coli thioredoxin-(SH)2 to phage T4 thioredoxin-S2.", "content": "Thioredoxin from Escherichia coli B and phage T4-infected E. coli B are small hydrogen carrier proteins which in their reduced forms are specific hydrogen donors to E. coli and T4-induced ribonucleotide reductase, respectively. The oxidation-reduction active group of both thioredoxins consists of a single cystine residue which is reduced to sulfhydryl form by NADPH in the presence of E. coli thioredoxin reductase. Reduction of T4 thioredoxin-S2 to thioredoxin-(SH)2 led to a 3-fold increase in the quantum yield of tyrosine fluorescence. By using the spectrofluorimetric properties of T4 thioredoxin and E. coli thioredoxin as markers for their oxidized and reduced forms we have shown that E. coli thioredoxin reductase catalyzed the reaction: (see article) whose equilibrium constant favors formation of E. coli thioredoxin-S2 and T4 thioredoxin-(SH)2. This finding suggests that in the T4-infected cell most of the deoxyribonucleotides required for the viral DNA might be synthesized by the T4-induced ribonucleotide reductase while the host ribonucleotide reductase is inactive due to the shortage of reduced E. coli thioredoxin.", "contents": "Thioredoxin reductase-mediated hydrogen transfer from Escherichia coli thioredoxin-(SH)2 to phage T4 thioredoxin-S2. Thioredoxin from Escherichia coli B and phage T4-infected E. coli B are small hydrogen carrier proteins which in their reduced forms are specific hydrogen donors to E. coli and T4-induced ribonucleotide reductase, respectively. The oxidation-reduction active group of both thioredoxins consists of a single cystine residue which is reduced to sulfhydryl form by NADPH in the presence of E. coli thioredoxin reductase. Reduction of T4 thioredoxin-S2 to thioredoxin-(SH)2 led to a 3-fold increase in the quantum yield of tyrosine fluorescence. By using the spectrofluorimetric properties of T4 thioredoxin and E. coli thioredoxin as markers for their oxidized and reduced forms we have shown that E. coli thioredoxin reductase catalyzed the reaction: (see article) whose equilibrium constant favors formation of E. coli thioredoxin-S2 and T4 thioredoxin-(SH)2. This finding suggests that in the T4-infected cell most of the deoxyribonucleotides required for the viral DNA might be synthesized by the T4-induced ribonucleotide reductase while the host ribonucleotide reductase is inactive due to the shortage of reduced E. coli thioredoxin."}
{"id": "PMID:235529", "title": "Prostaglandin 9-hydroxydehydrogenase activity in the adult rat kidney. Identification, assay, pathway, and some enzyme properties.", "content": "Prostaglandin F2alpha is converted to 15-keto-13,14-dihydroprostaglandin E2 by adult rat kidney homogenates. A variety of substrates labeled as either the 9beta position alone or at several other positions in the prostaglandin molecule were used to define the step at which the crossover from the F type to the E type prostaglandins takes place. Time course studies further confirmed that 15-keto-13,14-dihydroprostaglandin F2alpha is the immediate substrate for this enzyme which we have termed prostaglandin 9-hydroxydehydrogenase. An assay system based on specific loss of tritium from 9beta-tritiated prostaglandin F2alpha is described. Enzyme activity with prostaglandin F2alpha as substrate is linear with time up to 10 min, stimulated by NAD+, saturable at low concentrations of substrate, stable to storage at minus 25 degrees in phosphate buffer (up to 3 weeks), and has a broad pH optimum around 7.5. The product, 15-keto,13,14-dihydroprostaglandin E2 was identified by mass spectrometry through a sodium borohydride-sodium borodeuteride reduction method.", "contents": "Prostaglandin 9-hydroxydehydrogenase activity in the adult rat kidney. Identification, assay, pathway, and some enzyme properties. Prostaglandin F2alpha is converted to 15-keto-13,14-dihydroprostaglandin E2 by adult rat kidney homogenates. A variety of substrates labeled as either the 9beta position alone or at several other positions in the prostaglandin molecule were used to define the step at which the crossover from the F type to the E type prostaglandins takes place. Time course studies further confirmed that 15-keto-13,14-dihydroprostaglandin F2alpha is the immediate substrate for this enzyme which we have termed prostaglandin 9-hydroxydehydrogenase. An assay system based on specific loss of tritium from 9beta-tritiated prostaglandin F2alpha is described. Enzyme activity with prostaglandin F2alpha as substrate is linear with time up to 10 min, stimulated by NAD+, saturable at low concentrations of substrate, stable to storage at minus 25 degrees in phosphate buffer (up to 3 weeks), and has a broad pH optimum around 7.5. The product, 15-keto,13,14-dihydroprostaglandin E2 was identified by mass spectrometry through a sodium borohydride-sodium borodeuteride reduction method."}
{"id": "PMID:235530", "title": "Kinetics of the oxidation of p-aminobenzoic acid catalyzed by horseradish peroxidase compounds I and II.", "content": "The kinetics of p-aminobenzoic acid oxidation catalyzed by horseradish peroxidase Compounds I and II was investigated intensively as a function of pH at 25 degrees in aqueous solutions of ionic strength 0.11. All of the rate data were collected from single turnover experiments involving reactions of a single enzyme compound. In reactions of both compounds, deviations from first order behavior with respect to the enzyme were observed at high pH values which were explained in terms of a free radical interaction of product with the enzyme. The effect could be eliminated with sufficient excess of substrate. Kinetic behavior which deviated from first order in substrate, observed at low pH, was explained by a mechanism involving an enzyme-substrate complex which reacted with an additional molecule of substrate but at a slower rate. The pH dependence of the second order rate constants for the reaction of p-aminobenzoic acid with free Compounds I and II is similar to results obtained for the comparable reactions of ferrocyanide, suggesting similar proton-transfer mechanisms for both reducing substrates. The reduction of Compound II by p-aminobenzoic acid appeared to be influenced by two ionizable groups on the enzyme which affect the electronic environment of the heme. The lack of influence of substrate ionizable groups on the rate of the Compound II reaction indicated that potential differences in reactivities of NH2C6H4COO- and NH2C6H4COOH were levelled by the diffusion-controlled limit in the acid region of pH. The reduction of Compound I by p-aminobenzoic acid was not diffusion-controlled and the rate-pH profile could be explained in terms of three acid ionizations, two on the substrate and one on Compound I.", "contents": "Kinetics of the oxidation of p-aminobenzoic acid catalyzed by horseradish peroxidase compounds I and II. The kinetics of p-aminobenzoic acid oxidation catalyzed by horseradish peroxidase Compounds I and II was investigated intensively as a function of pH at 25 degrees in aqueous solutions of ionic strength 0.11. All of the rate data were collected from single turnover experiments involving reactions of a single enzyme compound. In reactions of both compounds, deviations from first order behavior with respect to the enzyme were observed at high pH values which were explained in terms of a free radical interaction of product with the enzyme. The effect could be eliminated with sufficient excess of substrate. Kinetic behavior which deviated from first order in substrate, observed at low pH, was explained by a mechanism involving an enzyme-substrate complex which reacted with an additional molecule of substrate but at a slower rate. The pH dependence of the second order rate constants for the reaction of p-aminobenzoic acid with free Compounds I and II is similar to results obtained for the comparable reactions of ferrocyanide, suggesting similar proton-transfer mechanisms for both reducing substrates. The reduction of Compound II by p-aminobenzoic acid appeared to be influenced by two ionizable groups on the enzyme which affect the electronic environment of the heme. The lack of influence of substrate ionizable groups on the rate of the Compound II reaction indicated that potential differences in reactivities of NH2C6H4COO- and NH2C6H4COOH were levelled by the diffusion-controlled limit in the acid region of pH. The reduction of Compound I by p-aminobenzoic acid was not diffusion-controlled and the rate-pH profile could be explained in terms of three acid ionizations, two on the substrate and one on Compound I."}
{"id": "PMID:235531", "title": "Properties of the nicotinamide adenine dinucleotide phosphate-dependent aldehyde reductase from pig kidney. Amino acid composition, reactivity of cysteinyl residues, and stereochemistry of D-glyceraldehyde reduction.", "content": "Some physical and chemical properties of the monomeric NADP+-dependent aldehyde reductase (previously called TPN-L-hexonate dehydrogenase or D-glucuronate reductase) from pig kidney have been examined. The amino acid composition has been determined. Four of the five thiol groups react with p-mercuribenzoate at pH 7, with no resulting loss of catalytic activity. High concentrations of p-mercuribenzoate cause complete enzyme inhibition, which can be partly reversed by addition of aldehyde reductase is low (9%, estimated from the ellipticity at 208 nm), and 70 to 80% of the tyrosine and tryptophan residues aare buried within the molecule. One molecule of NADPH binds to the enzyme (Kp equal 25 muM), causing a blue shift and enhancement of the coenzyme fluorescence, and suggesting that the environment of the active site is hydrophobic. In the reduction of D-glyceraldehyde, catalyzed by aldehyde reductase, the pro-4R \"A\" hydrogen of NADPH attacks the re face of the carbonyl group. This stereospecificity is the same as in the reductions of D-glyceraldehyde and acetaldehyde effected by rabbit muscle dehydrogenase and liver alcohol dehydrogenase, respectively.", "contents": "Properties of the nicotinamide adenine dinucleotide phosphate-dependent aldehyde reductase from pig kidney. Amino acid composition, reactivity of cysteinyl residues, and stereochemistry of D-glyceraldehyde reduction. Some physical and chemical properties of the monomeric NADP+-dependent aldehyde reductase (previously called TPN-L-hexonate dehydrogenase or D-glucuronate reductase) from pig kidney have been examined. The amino acid composition has been determined. Four of the five thiol groups react with p-mercuribenzoate at pH 7, with no resulting loss of catalytic activity. High concentrations of p-mercuribenzoate cause complete enzyme inhibition, which can be partly reversed by addition of aldehyde reductase is low (9%, estimated from the ellipticity at 208 nm), and 70 to 80% of the tyrosine and tryptophan residues aare buried within the molecule. One molecule of NADPH binds to the enzyme (Kp equal 25 muM), causing a blue shift and enhancement of the coenzyme fluorescence, and suggesting that the environment of the active site is hydrophobic. In the reduction of D-glyceraldehyde, catalyzed by aldehyde reductase, the pro-4R \"A\" hydrogen of NADPH attacks the re face of the carbonyl group. This stereospecificity is the same as in the reductions of D-glyceraldehyde and acetaldehyde effected by rabbit muscle dehydrogenase and liver alcohol dehydrogenase, respectively."}
{"id": "PMID:235532", "title": "Cyanate modification of essential lysyl residues of the diphosphopyridine nucleotide-specific isocitrate dehydrogenase of pig heart.", "content": "The DPN-specific isocitrate dehydrogenase of pig heart is totally and irreversibly inactivated by 0.05 M potassium cyanate at pH 7.4 A plot of the rate constant versus cyanate concentration is not linear, but rather exhibits saturation kinetics, implying that cyanate may bind to the enzyme to give an enzyme-cyanate complex (K equal 0.125 M) prior to the covalent reaction. In the presence of manganous ion the addition of isocitrate protects the enzyme against cyanate inactivation, indicating that chemical modification occurs in the active site region of the enzyme. The dependence of the decrease of the rate constant for inactivation on the isocitrate concentration yields a dissociation constant for the enzyme-manganese-isocitrate complex which agrees with the Michaelis constant. The allosteric activator ADP, which lowers the Michaelis constant for isocitrate, does not itself significantly affect the cyanate reaction; however, it strikingly enhances the protection by isocitrate. The addition of the chelator EDTA essentially prevents protection by isocitrate and manganous ion, demonstrating the importance of the metal ion in this process. The substrate alpha-ketoglutarate and the coenzymes DPN and DPNH do not significantly affect the rate of modification of the enzymes by cyanate. Incubation of isocitrate dehydrogenase with 14C-labeled potassium cyanate leads to the incorporation of approximately 1 mol of radioactive cyanate per peptide chain concomitant with inactivation. Analysis of acid hydrolysates of the radioactive enzyme reveals that lysyl residues are the sole amino acids modified. These results suggest that cyanate, or isocyanic acid, may bind to the active site of this enzyme as an analogue of carbon dioxide and carbamylate a lysyl residue at the active site.", "contents": "Cyanate modification of essential lysyl residues of the diphosphopyridine nucleotide-specific isocitrate dehydrogenase of pig heart. The DPN-specific isocitrate dehydrogenase of pig heart is totally and irreversibly inactivated by 0.05 M potassium cyanate at pH 7.4 A plot of the rate constant versus cyanate concentration is not linear, but rather exhibits saturation kinetics, implying that cyanate may bind to the enzyme to give an enzyme-cyanate complex (K equal 0.125 M) prior to the covalent reaction. In the presence of manganous ion the addition of isocitrate protects the enzyme against cyanate inactivation, indicating that chemical modification occurs in the active site region of the enzyme. The dependence of the decrease of the rate constant for inactivation on the isocitrate concentration yields a dissociation constant for the enzyme-manganese-isocitrate complex which agrees with the Michaelis constant. The allosteric activator ADP, which lowers the Michaelis constant for isocitrate, does not itself significantly affect the cyanate reaction; however, it strikingly enhances the protection by isocitrate. The addition of the chelator EDTA essentially prevents protection by isocitrate and manganous ion, demonstrating the importance of the metal ion in this process. The substrate alpha-ketoglutarate and the coenzymes DPN and DPNH do not significantly affect the rate of modification of the enzymes by cyanate. Incubation of isocitrate dehydrogenase with 14C-labeled potassium cyanate leads to the incorporation of approximately 1 mol of radioactive cyanate per peptide chain concomitant with inactivation. Analysis of acid hydrolysates of the radioactive enzyme reveals that lysyl residues are the sole amino acids modified. These results suggest that cyanate, or isocyanic acid, may bind to the active site of this enzyme as an analogue of carbon dioxide and carbamylate a lysyl residue at the active site."}
{"id": "PMID:235533", "title": "Some physical and kinetic properties of adenylyl sulfate reductase from Desulfovibrio vulgaris.", "content": "Adenylyl sulfate reductase has been purified from the anaerobic sulfate-reducing bacterium, Desulfovibrio vulgaris, and judged to be homogenous by several criteria. Different forms of the enzyme could be visualized in polyacrylamide gels after electrophoresis and these polymeric species have been studied by a combination of absorption spectra, polyacrylamide gel electrophoresis, and sedimentation  velocity experiments. A dimeric species of molecular weight 440,000 is stable in potassium phosphate buffer but can be dissociated to a 220,000 molecular weight species by either changing the buffer system to Tris-maleate or addition of AMP, DAMP, or adenylyl sulfate. Other catalytically active nucleotides are not capable of effecting this dissociation. The enzyme was determined to contain 12 non-heme irons, 12 acid-labile sulfides, and 1 FAD per molecule when calculated on the basis of a monomeric molecular weight of 220,000. ;el electrophoresis in the presence of sodium dodecyl sulfate indicated subunits of molecular weight 72,000 and 20,000. The extinction coefficient when determined in phosphate buffer at 372 nm is 108,000 M-1 cm-a. Steady state kinetic experiments employing ferricyanide, cytochrome c, and reduced methyl viologen as artificial electron transfer reagents were performed and the kinetic constants obtained under various conditions. Several nucleotide substrates were employed and compared in each assay with respect to Km and Vmax. The reduction of cytochrome c was found to be sensitive to both anaerobiosis and superoxide dismutase, suggesting the involvement of superoxide anions with this electron acceptor.", "contents": "Some physical and kinetic properties of adenylyl sulfate reductase from Desulfovibrio vulgaris. Adenylyl sulfate reductase has been purified from the anaerobic sulfate-reducing bacterium, Desulfovibrio vulgaris, and judged to be homogenous by several criteria. Different forms of the enzyme could be visualized in polyacrylamide gels after electrophoresis and these polymeric species have been studied by a combination of absorption spectra, polyacrylamide gel electrophoresis, and sedimentation  velocity experiments. A dimeric species of molecular weight 440,000 is stable in potassium phosphate buffer but can be dissociated to a 220,000 molecular weight species by either changing the buffer system to Tris-maleate or addition of AMP, DAMP, or adenylyl sulfate. Other catalytically active nucleotides are not capable of effecting this dissociation. The enzyme was determined to contain 12 non-heme irons, 12 acid-labile sulfides, and 1 FAD per molecule when calculated on the basis of a monomeric molecular weight of 220,000. ;el electrophoresis in the presence of sodium dodecyl sulfate indicated subunits of molecular weight 72,000 and 20,000. The extinction coefficient when determined in phosphate buffer at 372 nm is 108,000 M-1 cm-a. Steady state kinetic experiments employing ferricyanide, cytochrome c, and reduced methyl viologen as artificial electron transfer reagents were performed and the kinetic constants obtained under various conditions. Several nucleotide substrates were employed and compared in each assay with respect to Km and Vmax. The reduction of cytochrome c was found to be sensitive to both anaerobiosis and superoxide dismutase, suggesting the involvement of superoxide anions with this electron acceptor."}
{"id": "PMID:235534", "title": "Malate dehydrogenase, circular dichroism difference spectra of porcine heart mitochondrial and supernatant enzymes, binary enzyme-coenzyme, and ternary enzyme-coenzyme-substrate analog complexes.", "content": "Circular dichroism spectra and circular dichroism difference spectra, generated when porcine heart mitochondrial and supernatant malate dehydrogenase bind coenzymes or when enzyme dihydroincotinamide nucleotide binary complexes bind substrate analogs, are presented. No significant changes are observed in protein chromophores in the 200- to 240-nm spectral range indicating that there is apparently little or no perturbation of the alpha helix or peptide backbone when binary or ternary complexes are formed. Quite different spectral perturbances occur in the two enzymes with reduced coenzyme binding as well as with substrate-analog binding by enzyme-reduced coenzyme binding. Comparison of spectral perturbations in both enzymes with oxidized or reduced coenzyme binding suggests that the dihydronicotinamide moiety of the coenzyme interacts with or perturbs indirectly the environment of aromatic amino acid residues. Reduced coenzyme binding apparently perturbs tyrosine residues in both mitochondrial malate dehydrogenase and lactic dehydrogenase. Reduced coenzyme binding perturbs tyrosine and tryptophan residues in supernatant malate dehydrogenase. The number of reduced coenzyme binding sites was determined to be two per 70,000 daltons in the mitochondrial enzyme, and the reduced coenzyme dissociation constants, determined through the change in ellipticity at 260 nm, with dihydronicotinamide adenine dinucleotide binding, were found to be good agreement with published values (Holbrook, J. J., and Wolfe, R. G. (1972) Biochemistry 11, 2499-2502) obtained through fluorescence-binding studies and indicate no apparent extra coenzyme binding sites. When D-malate forms a ternary complex with malate dehydrogenase-reduced coenzyme complexes, perturbation of both adenine and dihydronicotinamide chromophores is evident. L-Malate binding, however, apparently produces only a perturbation of the adenine chromophore in such complexes. Since the coenzyme has been found to bind in an open conformation on the surface of the enzyme and the substrate analogs bind at or very near the dihydronicotinamide moiety binding site, protein conformational changes are implicated during ternary complex formation with D-malate which can effect the adenine chromophore at some distance from the substrate binding site.", "contents": "Malate dehydrogenase, circular dichroism difference spectra of porcine heart mitochondrial and supernatant enzymes, binary enzyme-coenzyme, and ternary enzyme-coenzyme-substrate analog complexes. Circular dichroism spectra and circular dichroism difference spectra, generated when porcine heart mitochondrial and supernatant malate dehydrogenase bind coenzymes or when enzyme dihydroincotinamide nucleotide binary complexes bind substrate analogs, are presented. No significant changes are observed in protein chromophores in the 200- to 240-nm spectral range indicating that there is apparently little or no perturbation of the alpha helix or peptide backbone when binary or ternary complexes are formed. Quite different spectral perturbances occur in the two enzymes with reduced coenzyme binding as well as with substrate-analog binding by enzyme-reduced coenzyme binding. Comparison of spectral perturbations in both enzymes with oxidized or reduced coenzyme binding suggests that the dihydronicotinamide moiety of the coenzyme interacts with or perturbs indirectly the environment of aromatic amino acid residues. Reduced coenzyme binding apparently perturbs tyrosine residues in both mitochondrial malate dehydrogenase and lactic dehydrogenase. Reduced coenzyme binding perturbs tyrosine and tryptophan residues in supernatant malate dehydrogenase. The number of reduced coenzyme binding sites was determined to be two per 70,000 daltons in the mitochondrial enzyme, and the reduced coenzyme dissociation constants, determined through the change in ellipticity at 260 nm, with dihydronicotinamide adenine dinucleotide binding, were found to be good agreement with published values (Holbrook, J. J., and Wolfe, R. G. (1972) Biochemistry 11, 2499-2502) obtained through fluorescence-binding studies and indicate no apparent extra coenzyme binding sites. When D-malate forms a ternary complex with malate dehydrogenase-reduced coenzyme complexes, perturbation of both adenine and dihydronicotinamide chromophores is evident. L-Malate binding, however, apparently produces only a perturbation of the adenine chromophore in such complexes. Since the coenzyme has been found to bind in an open conformation on the surface of the enzyme and the substrate analogs bind at or very near the dihydronicotinamide moiety binding site, protein conformational changes are implicated during ternary complex formation with D-malate which can effect the adenine chromophore at some distance from the substrate binding site."}
{"id": "PMID:235535", "title": "A protein from Ustilago which forms an acid-soluble complex with deoxyribonucleic acid.", "content": "A protein which can render DNA largely acid-soluble has been purified 1600-fold from high salt extracts of Ustilago maydis. The activity is unusual in that substrate DNA is not made acid-soluble through hydrolysis to small oligomers. Rather, the protein appears to bind to DNA to form a complex which itself is acid-soluble. The activity of conversion of DNA to an acid-soluble form is cold-labile, but the inactivation by cold is reversible by brief heat treatment. Divalent cations stimulate the activity; phosphate is inhibitory. Optimal activity is observed at pH 6.0 and again at pH 9.0. Nucleoside triphosphates and diphosphates stimulate activity at low protein concentrations but are not hydrolyzed during the course of reaction. The protein behaves anomalously on gel filtration columns and is completely excluded by Sephadex or agarose gels. When analyzed by sedimentation velocity, the protein was found to sediment at 5.3 S, the same rate at which a globular protein of 65,000 daltons would sediment. Dependence of activity upon protein concentrations is sigmoidal. K+ and to a lesser degree NH4+ are partially effective in abolishing the lag in the concentration curve. The protein displays a saturation curve when exposed to increasing DNA concentrations. Such a curve could only result from a non-random or cooperative mode of binding of the protein to DNA. A mutant sensitive to gamma and ultraviolet radiation with an abnormally high level of the protein has been found. Haploid populations of the mutant grow slowly and contain a large proportion (10 to 20%) of inviable cells. Diploids are defective in mitotic allelic recombination and fail to complete meiosis. It is speculated that the protein may be important in the regulation of chromosome condensation.", "contents": "A protein from Ustilago which forms an acid-soluble complex with deoxyribonucleic acid. A protein which can render DNA largely acid-soluble has been purified 1600-fold from high salt extracts of Ustilago maydis. The activity is unusual in that substrate DNA is not made acid-soluble through hydrolysis to small oligomers. Rather, the protein appears to bind to DNA to form a complex which itself is acid-soluble. The activity of conversion of DNA to an acid-soluble form is cold-labile, but the inactivation by cold is reversible by brief heat treatment. Divalent cations stimulate the activity; phosphate is inhibitory. Optimal activity is observed at pH 6.0 and again at pH 9.0. Nucleoside triphosphates and diphosphates stimulate activity at low protein concentrations but are not hydrolyzed during the course of reaction. The protein behaves anomalously on gel filtration columns and is completely excluded by Sephadex or agarose gels. When analyzed by sedimentation velocity, the protein was found to sediment at 5.3 S, the same rate at which a globular protein of 65,000 daltons would sediment. Dependence of activity upon protein concentrations is sigmoidal. K+ and to a lesser degree NH4+ are partially effective in abolishing the lag in the concentration curve. The protein displays a saturation curve when exposed to increasing DNA concentrations. Such a curve could only result from a non-random or cooperative mode of binding of the protein to DNA. A mutant sensitive to gamma and ultraviolet radiation with an abnormally high level of the protein has been found. Haploid populations of the mutant grow slowly and contain a large proportion (10 to 20%) of inviable cells. Diploids are defective in mitotic allelic recombination and fail to complete meiosis. It is speculated that the protein may be important in the regulation of chromosome condensation."}
{"id": "PMID:235536", "title": "Involvement of tyrosine and lysine residues of retinol-binding protein in the interaction between retinol and retinol-binding protein and between retinol-binding protein and prealbumin. Acetylation with N-acetylimidazole and alkaline titration.", "content": "The behavior of holo-retinol-binding protein (RBP) from human plasma at alkaline pH was examined by absorption and circular dichroism measurements. Between pH 7.5 and 11.7 the ionization of the phenolic hydroxyl groups is reversible. However, there is a gradual irreversible loss of retinol as the pH is raised. After 4 hours at pH 11.7, 13 percent of retinol is lost from retinol-RBP. Alkaline titration of apo-RBP was time-independent and reversible between pH 7.5 and 11.7. The titration data of the phenolic hydroxyl groups in apo-RBP could be fitted with a single theoretical ionization curve of 8.6 phenolic groups having an apparent pK of 11. Acetylation of retinol-RBP with 10-fold molar excess of N-acetylimidazole over tyrosine resulted in the acetylation of all lysine residues and in the acetylation of 0.9 to 1.3 tyrosyl residues per molecule (out of eight). Acetylation of retinol-RBP, APO-RBP, and retinol-RBP-prealbumin complex with 50-fold molar excess of N-acetylimidazole resulted, again, with all of the lysine residues being acetylated and between 1.8 and 2.8 tyrosyl residues per molecule being acetylated. The acetylation did not affect the interaction between retinol and RBP. However, acetylation disrupted the normal binding between retinol-RBP and prealbumin. Deacetylation of tyrosyl residues with hydroxylamine failed to restore the normal binding of retinol-RBP to prealbumin. This excludes the acetylated tyrosyl-residues from being involved in the binding between the two proteins.", "contents": "Involvement of tyrosine and lysine residues of retinol-binding protein in the interaction between retinol and retinol-binding protein and between retinol-binding protein and prealbumin. Acetylation with N-acetylimidazole and alkaline titration. The behavior of holo-retinol-binding protein (RBP) from human plasma at alkaline pH was examined by absorption and circular dichroism measurements. Between pH 7.5 and 11.7 the ionization of the phenolic hydroxyl groups is reversible. However, there is a gradual irreversible loss of retinol as the pH is raised. After 4 hours at pH 11.7, 13 percent of retinol is lost from retinol-RBP. Alkaline titration of apo-RBP was time-independent and reversible between pH 7.5 and 11.7. The titration data of the phenolic hydroxyl groups in apo-RBP could be fitted with a single theoretical ionization curve of 8.6 phenolic groups having an apparent pK of 11. Acetylation of retinol-RBP with 10-fold molar excess of N-acetylimidazole over tyrosine resulted in the acetylation of all lysine residues and in the acetylation of 0.9 to 1.3 tyrosyl residues per molecule (out of eight). Acetylation of retinol-RBP, APO-RBP, and retinol-RBP-prealbumin complex with 50-fold molar excess of N-acetylimidazole resulted, again, with all of the lysine residues being acetylated and between 1.8 and 2.8 tyrosyl residues per molecule being acetylated. The acetylation did not affect the interaction between retinol and RBP. However, acetylation disrupted the normal binding between retinol-RBP and prealbumin. Deacetylation of tyrosyl residues with hydroxylamine failed to restore the normal binding of retinol-RBP to prealbumin. This excludes the acetylated tyrosyl-residues from being involved in the binding between the two proteins."}
{"id": "PMID:235537", "title": "Purification and regulation of fructose-1,6-bisphosphatase from Bacillus licheniformis.", "content": "The fructose-1,6-bisphosphatase (D-fructose-1,6-bisphosphate 1-phosphohydrolase, EC 3.1.3.11) from the spore-forming bacterium Bacillus licheniformis was purified approximately 800-fold (with a 20% yield of activity) by a procedure that included ammonium sulfate precipitation, precipitation by MnCl2, and gamma-alumina gel absorption. Catalysis by this enzyme in vitro was specific for fructose 1,6-bisphosphate (Km of approximately 20 muM) and proceeded optimally at pH 8.0 to 8.5. Fructose-1,6-bisphosphatase was found to be rapidly inactivated by incubation in the presence of AMP or in the absence of Mn2+. The AMP inactivation was prevented by adding P-enolpyruvate to the incubation mixture. The enzyme was slowly inactivated when incubated in the presence of stabilizing concentrations of Mn2+ (5 mM) at protein concentrations of less than 8 mg of protein per ml. An additional system is produced during sporulation which specifically inactivates fructose bisphosphatase in vitro. This system, which is distinctly different from the AMP inactivating system, can be blocked by P-enolpyruvate. This fructose bisphosphatase, like fructose bisphosphatases from other sources, was strongly inhibited by AMP, exhibiting a Ki of approximately 5 muM. This inhibition, however, could be completely overcome by P-enolpyruvate. P-enolpyruvate was also found to be an activator of the enzyme and exhibited a Km of approximately 2 muM. This activation was prevented in a competitive manner by AMP, exhibiting a Ki of approximately 5 muM. No other effector of fructose bisphosphatase was identified in an extensive search. The specific activity of fructose bisphosphatase in crude extracts was found to be independent of the stage of the life cycle of the bacterium or of the nature of the carbon-energy source supporting growth. Immunoprecipitation studies indicate that no new species of fructose biphosphatase is produced during gluconeogenic growth or sporulation. The enzyme extracted from cells under a variety of physiological conditions exhibited a molecular weight of about 5 times 10-5 as determined by sucrose density centrifugation. Therefore, it is proposed that a single constitutively synthesized fructose bisphosphatase is present in B. licheniformis. Measurements of the intracellular level of fructose 1,6-bisphosphate indicate that the variation in the level of substrate throughout growth (1 mM) and sporulation (0.3 mM) does not regulate the in vivo activity of this enzyme, since the Km of the enzyme for fructose 1,6-bisphosphate is approximately 10-fold lower than the lowest in vivo concentration of substrate. P-enolpyruvate is proposed as the major regulator of fructose bisphosphatase activity in vivo.", "contents": "Purification and regulation of fructose-1,6-bisphosphatase from Bacillus licheniformis. The fructose-1,6-bisphosphatase (D-fructose-1,6-bisphosphate 1-phosphohydrolase, EC 3.1.3.11) from the spore-forming bacterium Bacillus licheniformis was purified approximately 800-fold (with a 20% yield of activity) by a procedure that included ammonium sulfate precipitation, precipitation by MnCl2, and gamma-alumina gel absorption. Catalysis by this enzyme in vitro was specific for fructose 1,6-bisphosphate (Km of approximately 20 muM) and proceeded optimally at pH 8.0 to 8.5. Fructose-1,6-bisphosphatase was found to be rapidly inactivated by incubation in the presence of AMP or in the absence of Mn2+. The AMP inactivation was prevented by adding P-enolpyruvate to the incubation mixture. The enzyme was slowly inactivated when incubated in the presence of stabilizing concentrations of Mn2+ (5 mM) at protein concentrations of less than 8 mg of protein per ml. An additional system is produced during sporulation which specifically inactivates fructose bisphosphatase in vitro. This system, which is distinctly different from the AMP inactivating system, can be blocked by P-enolpyruvate. This fructose bisphosphatase, like fructose bisphosphatases from other sources, was strongly inhibited by AMP, exhibiting a Ki of approximately 5 muM. This inhibition, however, could be completely overcome by P-enolpyruvate. P-enolpyruvate was also found to be an activator of the enzyme and exhibited a Km of approximately 2 muM. This activation was prevented in a competitive manner by AMP, exhibiting a Ki of approximately 5 muM. No other effector of fructose bisphosphatase was identified in an extensive search. The specific activity of fructose bisphosphatase in crude extracts was found to be independent of the stage of the life cycle of the bacterium or of the nature of the carbon-energy source supporting growth. Immunoprecipitation studies indicate that no new species of fructose biphosphatase is produced during gluconeogenic growth or sporulation. The enzyme extracted from cells under a variety of physiological conditions exhibited a molecular weight of about 5 times 10-5 as determined by sucrose density centrifugation. Therefore, it is proposed that a single constitutively synthesized fructose bisphosphatase is present in B. licheniformis. Measurements of the intracellular level of fructose 1,6-bisphosphate indicate that the variation in the level of substrate throughout growth (1 mM) and sporulation (0.3 mM) does not regulate the in vivo activity of this enzyme, since the Km of the enzyme for fructose 1,6-bisphosphate is approximately 10-fold lower than the lowest in vivo concentration of substrate. P-enolpyruvate is proposed as the major regulator of fructose bisphosphatase activity in vivo."}
{"id": "PMID:235538", "title": "Dissociation of human follicle-stimulating hormone. Comparison with luteinizing hormone.", "content": "Rat testis tissue receptor assays were utilized to study the kinetics of dissociation of human follicle-stimulating hormone (hFSH) and luteinizing hormone (hLH) under varying conditions of urea concentration and pH. In these competitive protein binding assays, 125I-hFSH and 125I-hLH were the radioligands and hormone dissociation was followed by a decrease in the ability of the dissociating hormone to inhibit uptake of the radioligand by tissue receptors. Rate data for dissociation of the gonadotropins were analyzed for quality of fit to first or second order integrated rate equations by nonlinear regression analysis. Treatment of hFSH with 4 M urea at pH 8 and 25 degrees for 22 hours did not result in significant dissociation, whereas in 8 M urea, over 90% dissociation was observed. The rate of dissociation of hFSH in 8 M urea was increased approximately 4-fold by raising the temperature from 25 to 37 degrees. Similar results were obtained when dissociation of hFSH was followed through use of an accepted whole animal bioassay for FSH, thus confirming the reliability of the tissue receptor assay for such dissociation studies. Kinetic studies showed that hFSH was undissociated by incubation in 6 M urea of pH 8 after 4 hours at 25 degrees. In contrast, hLH was 90% dissociated under similar conditions. This differential rate of inactivation of hLH allowed preparation of hFSH having significant reduced levels of contaminating LH activity, as determined by tissue receptor assays and by whole animal bioassays. Marked differences were noted in the rate of dissociation of hFSH and hLH under acid conditions. hFSH completely dissociated after approximately 2 min of incubation of pH 2 (25 degrees), and over 90% dissociated after 15 min of incubation at pH 3. In contrast, hLH was dissociated 60% after 20 min of incubation at pH 2 (25 degrees) and 40% dissociated after 60 min at pH 3. Neither hormone was significantly dissociated at pH 4.4 after 60 min, but hFSH showed a slightly greater rate of dissociation than did LH in the period between 1 and 23 hours of incubation at that pH. hFSH and hLH were relatively resistant to dissociation after incubation at pH 12 for 1 hour, bu;t dissociated significantly after incubation for 22 hours at that pH. The time course for dissociation of hFSH or hLH under the various conditions described above did not conform clearly to either first or second order kinetics, indicating that the over-all dissociation process represents a mixed order reaction. It appears that urea or acid-induced denaturation of one or both subunits of hLH and hFSH may occur prior to their dissociation. The very rapid rate of dissociation at acid pH values, particularly of hFSH, indicate that ionic interactions contribute importantly to the subunit association phenomenon.", "contents": "Dissociation of human follicle-stimulating hormone. Comparison with luteinizing hormone. Rat testis tissue receptor assays were utilized to study the kinetics of dissociation of human follicle-stimulating hormone (hFSH) and luteinizing hormone (hLH) under varying conditions of urea concentration and pH. In these competitive protein binding assays, 125I-hFSH and 125I-hLH were the radioligands and hormone dissociation was followed by a decrease in the ability of the dissociating hormone to inhibit uptake of the radioligand by tissue receptors. Rate data for dissociation of the gonadotropins were analyzed for quality of fit to first or second order integrated rate equations by nonlinear regression analysis. Treatment of hFSH with 4 M urea at pH 8 and 25 degrees for 22 hours did not result in significant dissociation, whereas in 8 M urea, over 90% dissociation was observed. The rate of dissociation of hFSH in 8 M urea was increased approximately 4-fold by raising the temperature from 25 to 37 degrees. Similar results were obtained when dissociation of hFSH was followed through use of an accepted whole animal bioassay for FSH, thus confirming the reliability of the tissue receptor assay for such dissociation studies. Kinetic studies showed that hFSH was undissociated by incubation in 6 M urea of pH 8 after 4 hours at 25 degrees. In contrast, hLH was 90% dissociated under similar conditions. This differential rate of inactivation of hLH allowed preparation of hFSH having significant reduced levels of contaminating LH activity, as determined by tissue receptor assays and by whole animal bioassays. Marked differences were noted in the rate of dissociation of hFSH and hLH under acid conditions. hFSH completely dissociated after approximately 2 min of incubation of pH 2 (25 degrees), and over 90% dissociated after 15 min of incubation at pH 3. In contrast, hLH was dissociated 60% after 20 min of incubation at pH 2 (25 degrees) and 40% dissociated after 60 min at pH 3. Neither hormone was significantly dissociated at pH 4.4 after 60 min, but hFSH showed a slightly greater rate of dissociation than did LH in the period between 1 and 23 hours of incubation at that pH. hFSH and hLH were relatively resistant to dissociation after incubation at pH 12 for 1 hour, bu;t dissociated significantly after incubation for 22 hours at that pH. The time course for dissociation of hFSH or hLH under the various conditions described above did not conform clearly to either first or second order kinetics, indicating that the over-all dissociation process represents a mixed order reaction. It appears that urea or acid-induced denaturation of one or both subunits of hLH and hFSH may occur prior to their dissociation. The very rapid rate of dissociation at acid pH values, particularly of hFSH, indicate that ionic interactions contribute importantly to the subunit association phenomenon."}
{"id": "PMID:235539", "title": "The reaction of N-ethylmaleimide at the active site of succinate dehydrogenase.", "content": "Since 1938 mammalian succinate dehydrogenase has been thought to contain thiol groups at the active site. This hypothesis was questioned recently, because irreversible inhibition by bromopyruvate and N-ethylmaleimide appeared not to satisfy the requisite criteria for reaction at the active site. These recent observations of incomplete inactivation of succinate dehydrogenase by N-ethylmaleimide and incomplete protection by substrates can, however, be explained adequately by the presence of oxalacetate and other strong competitors of the inactivation process in the enzyme used in these studies. Substrates, competitive inhibitors, and anions which activate succinate dehydrogenase protect the enzyme from inhibition by N-ethylmaleimide. Inhibition of succinate dehydrogenase by N-ethylmaleimide involves at least two second order reactions which are pH dependent, with pKa values of 8.0 to 8.2. This pH dependence, the known reactivity of N-ethylmaleimide toward thiols, and the protection by substrate and competitive inhibitors indicate that sulfhydryl residues are required for catalytic activity and perform an essential, not secondary, role in the catalysis. Just as the presence of tightly bound oxalacetate prevents inhibition by N-ethylmaleimide, alkylation of the sulfhydryl residue(s) at the active site prevents the binding of [14C]oxalacetate. Thus, these thiol groups at the active site also may be the site of tight binding of oxalacetate during the activation-deactivation cycle.", "contents": "The reaction of N-ethylmaleimide at the active site of succinate dehydrogenase. Since 1938 mammalian succinate dehydrogenase has been thought to contain thiol groups at the active site. This hypothesis was questioned recently, because irreversible inhibition by bromopyruvate and N-ethylmaleimide appeared not to satisfy the requisite criteria for reaction at the active site. These recent observations of incomplete inactivation of succinate dehydrogenase by N-ethylmaleimide and incomplete protection by substrates can, however, be explained adequately by the presence of oxalacetate and other strong competitors of the inactivation process in the enzyme used in these studies. Substrates, competitive inhibitors, and anions which activate succinate dehydrogenase protect the enzyme from inhibition by N-ethylmaleimide. Inhibition of succinate dehydrogenase by N-ethylmaleimide involves at least two second order reactions which are pH dependent, with pKa values of 8.0 to 8.2. This pH dependence, the known reactivity of N-ethylmaleimide toward thiols, and the protection by substrate and competitive inhibitors indicate that sulfhydryl residues are required for catalytic activity and perform an essential, not secondary, role in the catalysis. Just as the presence of tightly bound oxalacetate prevents inhibition by N-ethylmaleimide, alkylation of the sulfhydryl residue(s) at the active site prevents the binding of [14C]oxalacetate. Thus, these thiol groups at the active site also may be the site of tight binding of oxalacetate during the activation-deactivation cycle."}
{"id": "PMID:235540", "title": "Characterization of the different polypeptide components and analysis of subunit assembly in ferritin.", "content": "Ferritin was dissociated into subunits by various denaturants and the subunits were examined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Human, horse, rat, and rabbit ferritins all exhibited characteristic patterns of heterogeneity; components with molecular weights of about 19,000, 11,000, and 8,000 were invariably found in these preparations. This result contradicts earlier reports that ferritin consists of 24 identical subunits. These polypeptides were isolated, purified in the presence of low concentrations of detergent, and characterized. Evidence based on amino acid compositions, NH2-terminal analysis and investigation of detergent-induced breakdown products, indicated that the 19,000 molecular weight component is a composite of the 8,000 and 11,000 molecular weight chains. Circular dichroism studies showed that the 19,000 molecular weight polypeptide retained appreciable amounts of ordered secondary structure whereas the two lower molecular weight peptides were unfolded to a much greater extent. If the 8,000 and 11,000 molecular weight polypeptides were recombined in equimolar amounts and the denaturant was completely removed, a substance with electrophoretic mobility and morphological appearance of native apoferritin was obtained.", "contents": "Characterization of the different polypeptide components and analysis of subunit assembly in ferritin. Ferritin was dissociated into subunits by various denaturants and the subunits were examined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Human, horse, rat, and rabbit ferritins all exhibited characteristic patterns of heterogeneity; components with molecular weights of about 19,000, 11,000, and 8,000 were invariably found in these preparations. This result contradicts earlier reports that ferritin consists of 24 identical subunits. These polypeptides were isolated, purified in the presence of low concentrations of detergent, and characterized. Evidence based on amino acid compositions, NH2-terminal analysis and investigation of detergent-induced breakdown products, indicated that the 19,000 molecular weight component is a composite of the 8,000 and 11,000 molecular weight chains. Circular dichroism studies showed that the 19,000 molecular weight polypeptide retained appreciable amounts of ordered secondary structure whereas the two lower molecular weight peptides were unfolded to a much greater extent. If the 8,000 and 11,000 molecular weight polypeptides were recombined in equimolar amounts and the denaturant was completely removed, a substance with electrophoretic mobility and morphological appearance of native apoferritin was obtained."}
{"id": "PMID:235541", "title": "The effects of inositol hexaphosphate on the allosteric properties of two beta-99-substituted abnormal hemoglobins, hemoglobin Yakima and hemoglobin Kempsey.", "content": "Hemoglobins (Hb) Yakima and Kempsey were purified from patients' blood with diethylaminoethyl cellulose column chromatography. The oxygen equilibrium curves of the two hemoglobins and the effects of organic phosphates on the function were investigated. In 0.1 M phosphate buffer, Hill's constants n for Hb Yakima and Hb Kempsey were 1.0 to 1.1 at the pH range for 6.5 to 8.0 and the oxygen affinities of both the mutant hemoglobins were about 15 to 20 times that of Hb A at pH 7.0. The Bohr effect was normal in Hb Yakima and one-fourth normal in Hb Kempsey. In the presence of inositol hexaphosphate, the oxygen affinities to Hb Yakima and Hb Kempsey were greatly decreased, and an interesting result revealed that these hemoglobins showed clear cooperativity in oxygen binding. Hill's constant n in the presence of inositol hexaphosphate was 1.9 for Hb Kempsey and 2.3 for Hb Yakima at pH 7.0. The cooperativities of these mutant hemoglobins were pH-dependent, and Hb Kempsey showed high cooperativity at low pH (n equal 2.1 at pH 6.6) and low cooperativity at high pH (n equal 1.0 at pH 8.0). Hb Yakima showed similar pH dependence in cooperativity. In the presence of inositol hexaphosphate, Hb A showed a pH-dependent cooperativity different from those of Hb Yakima and Hb Kempsey, namely, Hill's n was the highest in alkaline pH (n equal 3.0 at pH 8.0) and decreased at lower pH (n equal 1.5 at pH 6.5). 2,3Diphosphoglycerate bound with the deoxygenated Hb Yakima and Hb Kempsey, however, had no effect on the oxygen binding of these abnormal hemoglobin. The pH-dependent cooperativity of alpha1beta2 contact anomalous hemoglobin and normal hemoglobin was explained by the shifts in the equilibrium between the high and low ligand affinity forms.", "contents": "The effects of inositol hexaphosphate on the allosteric properties of two beta-99-substituted abnormal hemoglobins, hemoglobin Yakima and hemoglobin Kempsey. Hemoglobins (Hb) Yakima and Kempsey were purified from patients' blood with diethylaminoethyl cellulose column chromatography. The oxygen equilibrium curves of the two hemoglobins and the effects of organic phosphates on the function were investigated. In 0.1 M phosphate buffer, Hill's constants n for Hb Yakima and Hb Kempsey were 1.0 to 1.1 at the pH range for 6.5 to 8.0 and the oxygen affinities of both the mutant hemoglobins were about 15 to 20 times that of Hb A at pH 7.0. The Bohr effect was normal in Hb Yakima and one-fourth normal in Hb Kempsey. In the presence of inositol hexaphosphate, the oxygen affinities to Hb Yakima and Hb Kempsey were greatly decreased, and an interesting result revealed that these hemoglobins showed clear cooperativity in oxygen binding. Hill's constant n in the presence of inositol hexaphosphate was 1.9 for Hb Kempsey and 2.3 for Hb Yakima at pH 7.0. The cooperativities of these mutant hemoglobins were pH-dependent, and Hb Kempsey showed high cooperativity at low pH (n equal 2.1 at pH 6.6) and low cooperativity at high pH (n equal 1.0 at pH 8.0). Hb Yakima showed similar pH dependence in cooperativity. In the presence of inositol hexaphosphate, Hb A showed a pH-dependent cooperativity different from those of Hb Yakima and Hb Kempsey, namely, Hill's n was the highest in alkaline pH (n equal 3.0 at pH 8.0) and decreased at lower pH (n equal 1.5 at pH 6.5). 2,3Diphosphoglycerate bound with the deoxygenated Hb Yakima and Hb Kempsey, however, had no effect on the oxygen binding of these abnormal hemoglobin. The pH-dependent cooperativity of alpha1beta2 contact anomalous hemoglobin and normal hemoglobin was explained by the shifts in the equilibrium between the high and low ligand affinity forms."}
{"id": "PMID:235542", "title": "Regulation of dopamine beta-hydroxylase in rat adrenal glands.", "content": "Rat adrenal gland levels of dopamine beta-hydroxylase are subject to dual control. Activation of the splanchnic nerves to the adrenal medulla by reserpine induces the synthesis of dopamine beta-hydroxylase without altering the rate of enzyme degradation. In contrast, hypophysectomy causes a decline in steady state dopamine beta-hydroxylase levels by first accelerating the rate of degradation, then by slowing the rate of enzyme synthesis as well. Adrenocorticotropic hormone administration partially reversed the effect of hypophysectomy on dopamin beta-hydroxylase degradation. These findings suggest that the trans-synaptic factors controlling dopamine beta-hydroxylase induction act by a different mechanism (enzyme synthesis) than the hormonal controls regulating steady state levels (enzyme degradation). Thus, active inhibition of enzyme degradation may be an important control in maintenance of steady state enzyme levels.", "contents": "Regulation of dopamine beta-hydroxylase in rat adrenal glands. Rat adrenal gland levels of dopamine beta-hydroxylase are subject to dual control. Activation of the splanchnic nerves to the adrenal medulla by reserpine induces the synthesis of dopamine beta-hydroxylase without altering the rate of enzyme degradation. In contrast, hypophysectomy causes a decline in steady state dopamine beta-hydroxylase levels by first accelerating the rate of degradation, then by slowing the rate of enzyme synthesis as well. Adrenocorticotropic hormone administration partially reversed the effect of hypophysectomy on dopamin beta-hydroxylase degradation. These findings suggest that the trans-synaptic factors controlling dopamine beta-hydroxylase induction act by a different mechanism (enzyme synthesis) than the hormonal controls regulating steady state levels (enzyme degradation). Thus, active inhibition of enzyme degradation may be an important control in maintenance of steady state enzyme levels."}
{"id": "PMID:235543", "title": "Glycoprotein biosynthesis: studies on thyroid mannosyltransferases. I. Action on glycopeptides and simple glycosides.", "content": "A particulate fraction from calf thyroid catalyzes the transfer of mannose from GDP-mannose to exogenous glycopeptides and methyl or aryl glycosides to form alpha-D-mannopyranosyl-D-mannose sequences. The transfer to the simple glycosides required a single nonreducing mannose residue linked to a lipophilic aglycone. Thus p-nitrophenyl-, 4-methylumbelliferyl-, phenyl- and methyl-alpha-D-mannopyranosides were effective acceptors while free mannose and glycosides of several other sugars were totally inactive. The Km value for methyl-alpha-D-mannopyranoside was 2.6 mM. Specificity for the anomeric configuration of the acceptor was glycosylated to the extent of 50% of the alpha anomer and mutual inhibition between these two acceptors was observed. Acetolysis or mild acid hydrolysis of the 14C-labeled products from the glycoside acceptors yielded the disaccharide, 2-O-alpha-D-mannopyranosyl-D-mannose, which represents the predominant linkage between mannose residues in the carbohydrate unit A of thyroglobulin. Glycopeptides with mannose sequences served as acceptors for the transfer reaction but only after dinitrophenylation of their peptide portion. The unit A glycopeptides of thyroglobulin with 10 mannose residues (Km equals 0.89 mM) were much better acceptors than glycopeptides containing the core portion of unit B which contains only three mannose components. Reduction in size of unit A glycopeptide acceptors by timed alpha-mannosidase treatment resulted in a progressive decrease in activity. Peptide-free unit A was inactive even after it was modified to carry dinitrophenyl groups on its glucosamine residues. GDP-mannose was the most effective glycosyl donor, with a Km value of 1.4 muM for methyl-alpha-D-mannopyranoside and 0.30 muM for dinitrophenyl unit A glycopeptides, although  ADP- and UDP-mannose could substitute to the extent of 40 to 45%. The mannose transfer to the glycopeptides had a optimum of 6.3 while that to the simple glycopeptides was best at pH 7.0. Both types of transfer reactions required a divalent cation with manganese serving most effectively in that capacity. Mannoslytransferase activity for both groups of acceptors was found predominantly in particulate subcellular fractions. A number of aromatic compounds and reagents which are disruptive of membrane integrity caused loss of enzyme activity presumably by interfering with the function of the lipophilic substituents on the various acceptors.", "contents": "Glycoprotein biosynthesis: studies on thyroid mannosyltransferases. I. Action on glycopeptides and simple glycosides. A particulate fraction from calf thyroid catalyzes the transfer of mannose from GDP-mannose to exogenous glycopeptides and methyl or aryl glycosides to form alpha-D-mannopyranosyl-D-mannose sequences. The transfer to the simple glycosides required a single nonreducing mannose residue linked to a lipophilic aglycone. Thus p-nitrophenyl-, 4-methylumbelliferyl-, phenyl- and methyl-alpha-D-mannopyranosides were effective acceptors while free mannose and glycosides of several other sugars were totally inactive. The Km value for methyl-alpha-D-mannopyranoside was 2.6 mM. Specificity for the anomeric configuration of the acceptor was glycosylated to the extent of 50% of the alpha anomer and mutual inhibition between these two acceptors was observed. Acetolysis or mild acid hydrolysis of the 14C-labeled products from the glycoside acceptors yielded the disaccharide, 2-O-alpha-D-mannopyranosyl-D-mannose, which represents the predominant linkage between mannose residues in the carbohydrate unit A of thyroglobulin. Glycopeptides with mannose sequences served as acceptors for the transfer reaction but only after dinitrophenylation of their peptide portion. The unit A glycopeptides of thyroglobulin with 10 mannose residues (Km equals 0.89 mM) were much better acceptors than glycopeptides containing the core portion of unit B which contains only three mannose components. Reduction in size of unit A glycopeptide acceptors by timed alpha-mannosidase treatment resulted in a progressive decrease in activity. Peptide-free unit A was inactive even after it was modified to carry dinitrophenyl groups on its glucosamine residues. GDP-mannose was the most effective glycosyl donor, with a Km value of 1.4 muM for methyl-alpha-D-mannopyranoside and 0.30 muM for dinitrophenyl unit A glycopeptides, although  ADP- and UDP-mannose could substitute to the extent of 40 to 45%. The mannose transfer to the glycopeptides had a optimum of 6.3 while that to the simple glycopeptides was best at pH 7.0. Both types of transfer reactions required a divalent cation with manganese serving most effectively in that capacity. Mannoslytransferase activity for both groups of acceptors was found predominantly in particulate subcellular fractions. A number of aromatic compounds and reagents which are disruptive of membrane integrity caused loss of enzyme activity presumably by interfering with the function of the lipophilic substituents on the various acceptors."}
{"id": "PMID:235544", "title": "Biochemical aspects of cardiac muscle differentiation. Deoxyribonucleic acid synthesis and nuclear and cytoplasmic deoxyribonucleic acid polymerase activity.", "content": "DNA synthesis and DNA polymerase activity have been measured in terminally differentiating cardiac muscle of the rat. Incorporation of [3H]thymidine into DNA essentially ceases by the 17th day of postnatal development. Cardiac muscle of neonatal rats contains at least two molecular species of DNA polymerase: a 3.5 S DNA polymerase that can be extracted from nuclei with 0.2 m potassium phosphate and a 6 to 8 S soluble cytoplasmic DNA polymerase. The nuclear DNA polymerase in crude extracts has a pH optimum of 9.0 and is more active with native DNA than with denatured DNA as the primer-template. The cytoplasmic DNA polymerase in crude extracts has a pH optimum of 7.5 and is more active with denatured DNA. The activity of the 6 to 8 S cytoplasmic DNA polymerase decreases 80-fold from day 1 to day 17 after birth, which correlates temporally with the reduced rate of DNA synthesis. The activity of the 3.5 S nuclear DNA polymerase remains relatively constant throughout postnatal development. Mixing experiments (assay of neonatal enzyme extracts with adult enzyme extracts) gave additive results, suggesting that the decline in 6 to 8 S DNA polymerase activity apparently is not due to the presence of absence of soluble activators or inhibitors at different times during development. These studies may provide a system which can be used to investigate the control of DNA synthesis and cellular proliferation during the terminal stages of cardiac muscle differentiation.", "contents": "Biochemical aspects of cardiac muscle differentiation. Deoxyribonucleic acid synthesis and nuclear and cytoplasmic deoxyribonucleic acid polymerase activity. DNA synthesis and DNA polymerase activity have been measured in terminally differentiating cardiac muscle of the rat. Incorporation of [3H]thymidine into DNA essentially ceases by the 17th day of postnatal development. Cardiac muscle of neonatal rats contains at least two molecular species of DNA polymerase: a 3.5 S DNA polymerase that can be extracted from nuclei with 0.2 m potassium phosphate and a 6 to 8 S soluble cytoplasmic DNA polymerase. The nuclear DNA polymerase in crude extracts has a pH optimum of 9.0 and is more active with native DNA than with denatured DNA as the primer-template. The cytoplasmic DNA polymerase in crude extracts has a pH optimum of 7.5 and is more active with denatured DNA. The activity of the 6 to 8 S cytoplasmic DNA polymerase decreases 80-fold from day 1 to day 17 after birth, which correlates temporally with the reduced rate of DNA synthesis. The activity of the 3.5 S nuclear DNA polymerase remains relatively constant throughout postnatal development. Mixing experiments (assay of neonatal enzyme extracts with adult enzyme extracts) gave additive results, suggesting that the decline in 6 to 8 S DNA polymerase activity apparently is not due to the presence of absence of soluble activators or inhibitors at different times during development. These studies may provide a system which can be used to investigate the control of DNA synthesis and cellular proliferation during the terminal stages of cardiac muscle differentiation."}
{"id": "PMID:235545", "title": "Enhancement of the glutaminase activity of carbamyl phosphate synthetase by alterations in the interaction between the heavy and light subunits.", "content": "Glutamine-dependent carbamyl phosphate synthetase (from Escherichia coli) was previously shown to be composed of a light subunit (molecular weight similar to 42,000) which has the binding site for glutamine and a heavy subunit (molecular weight similar to 130,000) which has binding sites for the other reactants and allosteric effectors. The subunits may be separated with retention of catalytic activities; only the separated light subunit exhibits glutaminase activity. The previous finding that storage of the native enzyme at pH 9 at 0 degrees increased its glutaminase activity by about 25-fold was further investigated; such storage markedly decreased the glutamine- and ammonia-dependent synthetase activities of the enzyme. Treatment of the enzyme with p-hydroxymercuribenzoate led to transient increase of glutaminase activity followed by inhibition. When the enzyme was treated with N-ethylmaleimide or with 5,5'-dithiobis-(2-nitrobenzoate), the glutaminase activity was increased by about 250-fold with concomitant loss of synthetase activities. The enhancement of glutaminase produced by storage of the enzyme at pH 9 was associated with intermolecular disulfide bond formation and aggregation of the enzyme. Aggregation also was observed after extensive treatment of the enzyme with 5,5'-dithiobis-(2-nitrobenzoate) or N-ethylmaleimide. However, a moderate increase of glutaminase activity (about 30-fold) was observed without aggregation under conditions in which one sulfhydryl group on the light subunit reacted with either reagent. The findings suggest that the increased glutaminase activities observed here are associated with structural changes in the enzyme in which the intersubunit relationship is altered so as to uncouple the catalytic functions of the enzyme and to facilitate access of water to the glutamine binding site on the light subunit.", "contents": "Enhancement of the glutaminase activity of carbamyl phosphate synthetase by alterations in the interaction between the heavy and light subunits. Glutamine-dependent carbamyl phosphate synthetase (from Escherichia coli) was previously shown to be composed of a light subunit (molecular weight similar to 42,000) which has the binding site for glutamine and a heavy subunit (molecular weight similar to 130,000) which has binding sites for the other reactants and allosteric effectors. The subunits may be separated with retention of catalytic activities; only the separated light subunit exhibits glutaminase activity. The previous finding that storage of the native enzyme at pH 9 at 0 degrees increased its glutaminase activity by about 25-fold was further investigated; such storage markedly decreased the glutamine- and ammonia-dependent synthetase activities of the enzyme. Treatment of the enzyme with p-hydroxymercuribenzoate led to transient increase of glutaminase activity followed by inhibition. When the enzyme was treated with N-ethylmaleimide or with 5,5'-dithiobis-(2-nitrobenzoate), the glutaminase activity was increased by about 250-fold with concomitant loss of synthetase activities. The enhancement of glutaminase produced by storage of the enzyme at pH 9 was associated with intermolecular disulfide bond formation and aggregation of the enzyme. Aggregation also was observed after extensive treatment of the enzyme with 5,5'-dithiobis-(2-nitrobenzoate) or N-ethylmaleimide. However, a moderate increase of glutaminase activity (about 30-fold) was observed without aggregation under conditions in which one sulfhydryl group on the light subunit reacted with either reagent. The findings suggest that the increased glutaminase activities observed here are associated with structural changes in the enzyme in which the intersubunit relationship is altered so as to uncouple the catalytic functions of the enzyme and to facilitate access of water to the glutamine binding site on the light subunit."}
{"id": "PMID:235546", "title": "Adenovirus deoxyribonucleic acid replication. II. Synthesis of viral deoxyribonucleic acid in vitro by a nuclear membrane fraction from infected KB cells.", "content": "A cell-free system for the study of viral DNA replications was developed by the isolation of a nuclear membrane fraction \"DNA replication complex\" from adenovirus 2-infected human KB cells late after infection. This complex which possesses both DNA polymerase activity and a virus-specific endonuclease synthesizes exclusively virus-specific DNA sequences in vitro by a semiconservative mechanism. Analysis by rate zonal sedimentation in alkaline sucrose gradients showed that the products of the reaction are small DNA chains approximately 6 to 9 S, presumably \"Okazaki intermediates,\" that are not sealed under our in vitro conditions. Analysis by rate zonal sedimentation in neutral sucrose gradients showed that labeled viral DNA fragments are hydrogen bonded to viral 18 S DNA segments, 0.25 the size of the linear, viral 31 S DNA genome. The 18 S DNA is probably a specific cleavage product of the viral endonuclease found in the replication complex and could represent intermediates in viral DNA replication or degradation products.", "contents": "Adenovirus deoxyribonucleic acid replication. II. Synthesis of viral deoxyribonucleic acid in vitro by a nuclear membrane fraction from infected KB cells. A cell-free system for the study of viral DNA replications was developed by the isolation of a nuclear membrane fraction \"DNA replication complex\" from adenovirus 2-infected human KB cells late after infection. This complex which possesses both DNA polymerase activity and a virus-specific endonuclease synthesizes exclusively virus-specific DNA sequences in vitro by a semiconservative mechanism. Analysis by rate zonal sedimentation in alkaline sucrose gradients showed that the products of the reaction are small DNA chains approximately 6 to 9 S, presumably \"Okazaki intermediates,\" that are not sealed under our in vitro conditions. Analysis by rate zonal sedimentation in neutral sucrose gradients showed that labeled viral DNA fragments are hydrogen bonded to viral 18 S DNA segments, 0.25 the size of the linear, viral 31 S DNA genome. The 18 S DNA is probably a specific cleavage product of the viral endonuclease found in the replication complex and could represent intermediates in viral DNA replication or degradation products."}
{"id": "PMID:235547", "title": "Rabbit liver pyridoxamine (pyridoxine) 5'-phosphate oxidase. Purification and properties.", "content": "Pyridoxamine (pyridoxine) 5'-phosphate oxidase (EC 1.4.3.5) has been purified 2000-fold from rabbit liver. The enzyme preparation migrates as a single protein and activity band on analytical disc gels containing 4,7, or 9 percent acrylamide, and as a single protein band on sodium dodecyl sulfate acrylamide gels. The oxidase is, therefore, homogeneous by these criteria. The pure enzyme catalyzes the following reactions in the presence of FMN: (See journal for formula). These activities copurify in the ratio of 1:1:1. Apparent K-m values are 10 muM for pyridoxamine-P, 30 muM for pyridoxine-P, and 40 nM for FMN. Apparent K-m values for N-(phosphopyridoxyl)amines range from 3.1 times 10-5 M to 1.6 times 10-3 M. The dissociation constant for FMN binding, determined by quenching of protein fluorescence, is 20 nM. The pH optima for all three types of substrates are broad, with maxima near pH 9. The pH dependence of FMN binding, measured by quenching of flavin fluorescence, has the same shape as the substrate activity profile. The holoenzyme has absorption maxima red-shifted from those of FMN to 380 nm and 448 nm, and exhibits spectral changes typical of flavoproteins upon reduction with dithionite. Its oxidation-reduction potential at pH 7 in phosphate buffer is -0.131 volt. The native enzyme has a molecular weight of 54,000 and is made up of two possibly identical polypeptide chains with molecular weights of 27,000. The applicability of proposed mechanisms of flavin catalysis to this flavoprotein is discussed.", "contents": "Rabbit liver pyridoxamine (pyridoxine) 5'-phosphate oxidase. Purification and properties. Pyridoxamine (pyridoxine) 5'-phosphate oxidase (EC 1.4.3.5) has been purified 2000-fold from rabbit liver. The enzyme preparation migrates as a single protein and activity band on analytical disc gels containing 4,7, or 9 percent acrylamide, and as a single protein band on sodium dodecyl sulfate acrylamide gels. The oxidase is, therefore, homogeneous by these criteria. The pure enzyme catalyzes the following reactions in the presence of FMN: (See journal for formula). These activities copurify in the ratio of 1:1:1. Apparent K-m values are 10 muM for pyridoxamine-P, 30 muM for pyridoxine-P, and 40 nM for FMN. Apparent K-m values for N-(phosphopyridoxyl)amines range from 3.1 times 10-5 M to 1.6 times 10-3 M. The dissociation constant for FMN binding, determined by quenching of protein fluorescence, is 20 nM. The pH optima for all three types of substrates are broad, with maxima near pH 9. The pH dependence of FMN binding, measured by quenching of flavin fluorescence, has the same shape as the substrate activity profile. The holoenzyme has absorption maxima red-shifted from those of FMN to 380 nm and 448 nm, and exhibits spectral changes typical of flavoproteins upon reduction with dithionite. Its oxidation-reduction potential at pH 7 in phosphate buffer is -0.131 volt. The native enzyme has a molecular weight of 54,000 and is made up of two possibly identical polypeptide chains with molecular weights of 27,000. The applicability of proposed mechanisms of flavin catalysis to this flavoprotein is discussed."}
{"id": "PMID:235548", "title": "A specific enzyme for glucose 1,6-bisphosphate synthesis.", "content": "The reaction: glycerate-1,3-P2 PLUS GLUCOSE-1-P YIELDS TO GLUCOSE-1,6-P2 plus glycerate-P is catalyzed by a distinct enzyme of mouse brain. A divalent metal requirement was shown when the enzyme was treated with imidazole and EDTA. Mg2+, Mn2+, Ca2+, Zn2+, Ni2+, Co2+, and Cd2+ were quite effective cofactors. The enzyme, in better than 50 percent yield, has been purified away from 99 percent of the phosphoglucomutase, phosphoglycrate mutase, and phosphofructokinase. Acetyl-P, ATP, enolpyruvate-P, creatine-P, and fructose-1,6-P2 are not phosphoryl donors. Glucose-6-P and mannose-1-P are good alternate acceptors. Mannose-6-P, galactose-Ps, and fructose-Ps have little or no acceptor activity. Strong inhibition was found with fructose-1,6-P2, glycerate-2,3-P2, enolpyruvate-P, and acetyl CoA. From the amount of activity and the kinetic constants of the purified enzyme it seems likely that this enzyme is responsible for the glucose-1,6-P2 synthesis of brain.", "contents": "A specific enzyme for glucose 1,6-bisphosphate synthesis. The reaction: glycerate-1,3-P2 PLUS GLUCOSE-1-P YIELDS TO GLUCOSE-1,6-P2 plus glycerate-P is catalyzed by a distinct enzyme of mouse brain. A divalent metal requirement was shown when the enzyme was treated with imidazole and EDTA. Mg2+, Mn2+, Ca2+, Zn2+, Ni2+, Co2+, and Cd2+ were quite effective cofactors. The enzyme, in better than 50 percent yield, has been purified away from 99 percent of the phosphoglucomutase, phosphoglycrate mutase, and phosphofructokinase. Acetyl-P, ATP, enolpyruvate-P, creatine-P, and fructose-1,6-P2 are not phosphoryl donors. Glucose-6-P and mannose-1-P are good alternate acceptors. Mannose-6-P, galactose-Ps, and fructose-Ps have little or no acceptor activity. Strong inhibition was found with fructose-1,6-P2, glycerate-2,3-P2, enolpyruvate-P, and acetyl CoA. From the amount of activity and the kinetic constants of the purified enzyme it seems likely that this enzyme is responsible for the glucose-1,6-P2 synthesis of brain."}
{"id": "PMID:235549", "title": "Use of the sodium borohydride reduction technique to identify a gamma-glutamyl phosphate intermediary in the Escherichia coli glutamine synthetase reaction.", "content": "Incubation of unadenylylated Escherichia coli glutamine synthetase with ATP, L-[14C]glutamate and metal ion results in the formation of gamma-glutamyl-P which can under appropriate conditions be reduced by sodium borohydride. The acyl-P compound is formed catalytically as judged by the quantity of radioactive alpha-amino-delta-hydroxyvalerate produced compared to the concentration of enzyme subunits. Formation of the glutamyl-P compound occurs in the presence of magnesium or manganous ions, and the relation of this apparent lack of metal ion specificity with regard to the highly specific Mg2+-supported biosynthetic activity of the unadenylylated form is discussed.", "contents": "Use of the sodium borohydride reduction technique to identify a gamma-glutamyl phosphate intermediary in the Escherichia coli glutamine synthetase reaction. Incubation of unadenylylated Escherichia coli glutamine synthetase with ATP, L-[14C]glutamate and metal ion results in the formation of gamma-glutamyl-P which can under appropriate conditions be reduced by sodium borohydride. The acyl-P compound is formed catalytically as judged by the quantity of radioactive alpha-amino-delta-hydroxyvalerate produced compared to the concentration of enzyme subunits. Formation of the glutamyl-P compound occurs in the presence of magnesium or manganous ions, and the relation of this apparent lack of metal ion specificity with regard to the highly specific Mg2+-supported biosynthetic activity of the unadenylylated form is discussed."}
{"id": "PMID:235550", "title": "The esterase activity of bovine carbonic anhydrase B above pH 9. Reversible and cooalent inhibition by acetozolamide.", "content": "The reversible complex between the metalloenzyme bovine carbonic anhydrase B and the sulfonamide inhibitor acetazolamide can be \"frozen\" irreversibly by the addition of a covalent bond between the methyl group of the inhibitor and the tau-nitrogen of histidine-64. In both cases the inhibited enzyme is inactive as an esterase toward p-nitrophenyl propionate at physiological pH but retains activity controlled by an ionization in the protein exhibiting a pK-a greater than 10. Similarly, both the covalently and reversibly inhibited enzymes in which the catalytically essential Zn(II) ion has been replaced with Co(II) display the same visible absorption spectrum which is invariant over the pH range from 5 to 12. The evidence therefore indicates that the position of the acetazolamide moiety in the active site is independent of both pH and the presence of the covalent bond to histidine-64. Moreover, when reversibly bound, this inhibitor has been shown to replace the water molecule (or hydroxide ion) known to occupy the fourth coordination position of the metal ion and frequently implicated in the catalytic mechanism of carbonic anhydrases. Thus, the activity exhibited by the inhibited enzymes and consequently the second rise observed in the pH rate profile of the native enzyme above pH 0 cannot reflect the ionization of such a water molecule in contrast to what has been postulated previously (Pocker, Y., and Storm, D. R. (1968) Biochemistry 7, 1202-1214). Displacement of the zinc-bound solvent molecule rather than the alkylation of histidine-64 is suggested, however, as the cause of the inactivation of the alkylated enzyme round neutrality. Taken together, the biphasic pH rate profile of native bovine carbonic anhydrase B as well as the activity retained by the alkylated enzyme above pH 9 are best described by a model in which two groups in the enzyme ionize independently, thereby raising the possibility that the high pH activity is controlled by an ionization outside the active site region of the enzyme. Above pH 9.5 the pK; for the reversible interaction between native carbonic anhydrase and acetazolamide falls off linearly with increasing pH. The slope of --1.56 suggests that, among other factors, more than one ionization is responsible for the descending limb of the pH-i-pH profile.", "contents": "The esterase activity of bovine carbonic anhydrase B above pH 9. Reversible and cooalent inhibition by acetozolamide. The reversible complex between the metalloenzyme bovine carbonic anhydrase B and the sulfonamide inhibitor acetazolamide can be \"frozen\" irreversibly by the addition of a covalent bond between the methyl group of the inhibitor and the tau-nitrogen of histidine-64. In both cases the inhibited enzyme is inactive as an esterase toward p-nitrophenyl propionate at physiological pH but retains activity controlled by an ionization in the protein exhibiting a pK-a greater than 10. Similarly, both the covalently and reversibly inhibited enzymes in which the catalytically essential Zn(II) ion has been replaced with Co(II) display the same visible absorption spectrum which is invariant over the pH range from 5 to 12. The evidence therefore indicates that the position of the acetazolamide moiety in the active site is independent of both pH and the presence of the covalent bond to histidine-64. Moreover, when reversibly bound, this inhibitor has been shown to replace the water molecule (or hydroxide ion) known to occupy the fourth coordination position of the metal ion and frequently implicated in the catalytic mechanism of carbonic anhydrases. Thus, the activity exhibited by the inhibited enzymes and consequently the second rise observed in the pH rate profile of the native enzyme above pH 0 cannot reflect the ionization of such a water molecule in contrast to what has been postulated previously (Pocker, Y., and Storm, D. R. (1968) Biochemistry 7, 1202-1214). Displacement of the zinc-bound solvent molecule rather than the alkylation of histidine-64 is suggested, however, as the cause of the inactivation of the alkylated enzyme round neutrality. Taken together, the biphasic pH rate profile of native bovine carbonic anhydrase B as well as the activity retained by the alkylated enzyme above pH 9 are best described by a model in which two groups in the enzyme ionize independently, thereby raising the possibility that the high pH activity is controlled by an ionization outside the active site region of the enzyme. Above pH 9.5 the pK; for the reversible interaction between native carbonic anhydrase and acetazolamide falls off linearly with increasing pH. The slope of --1.56 suggests that, among other factors, more than one ionization is responsible for the descending limb of the pH-i-pH profile."}
{"id": "PMID:235551", "title": "Properties of a reconstituted calcium pump.", "content": "1. The translocation of 45Ca2+ in vesicles reconstituted with purified Ca2+ ATPase of sarcoplasmic reticulum and phospholipids was dependent on ATP and varied greatly with the composition of the phospholipids. 2. In contrast to sarcoplasmic reticulum fragments, the reconstituted vesicles were impermeable to 14C-labeled oxalate, 3H- or 32P-labeled ATP, or 32P-i. There was no translocation of phosphate from gamma-labeled ATP during Ca2+ uptake. These results are inconsistent with some current formulations of the mechanism of pump action. 3. Reversal of the Ca2+ pump and generation of ATP and ADP and P-i was observed when vesicles loaded with Ca2+ were exposed to ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid. 4. Experiments on the formation of phosphoenzyme with 32P-labeled ATP showed that most if not all functional ATPase molecules in the reconstituted vesicles were oriented in the same direction, as in the case of sarcoplasmic reticulum fragments.", "contents": "Properties of a reconstituted calcium pump. 1. The translocation of 45Ca2+ in vesicles reconstituted with purified Ca2+ ATPase of sarcoplasmic reticulum and phospholipids was dependent on ATP and varied greatly with the composition of the phospholipids. 2. In contrast to sarcoplasmic reticulum fragments, the reconstituted vesicles were impermeable to 14C-labeled oxalate, 3H- or 32P-labeled ATP, or 32P-i. There was no translocation of phosphate from gamma-labeled ATP during Ca2+ uptake. These results are inconsistent with some current formulations of the mechanism of pump action. 3. Reversal of the Ca2+ pump and generation of ATP and ADP and P-i was observed when vesicles loaded with Ca2+ were exposed to ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid. 4. Experiments on the formation of phosphoenzyme with 32P-labeled ATP showed that most if not all functional ATPase molecules in the reconstituted vesicles were oriented in the same direction, as in the case of sarcoplasmic reticulum fragments."}
{"id": "PMID:235552", "title": "Purification and properties of guanosine triphosphate cyclohydrolase II from Escherichia coli.", "content": "An enzyme that uses GTP as substrate for the formation in stoichiometric quantities of formate, inorganic pyrophosphate, and 2,5-diamino-6-hydroxy-4-(ribosylamino)pyrimidine-5'-phosphate has been purified 2200-fold from extracts of Escherichia coli B. This enzyme is named GTP cyclohydrolase II to distinguish it from a previously studied E. coli enzyme, named GTP cyclohydrolase (and called GTP cyclohydrolase I in this paper), that catalyzes the first of a series of enzymatic reactions leading to the biosynthesis of the pteridine portion of folic acid (Burg, A. W., and Brown, G. M. (1968) J. Biol. Chem. 243, 2349-2358). Some of the properties of GTP cyclohydrolase II are: (a) divalent cations are required for activity (Mg2+ is most effective); (b) its molecular weight, estimated by filtration on Sephadex G-200, is 44,000; (c) the K-m for GTP is 41 mum; (d) its pH optimum is 8.5; and (e) its activity is inhibited by inorganic pyrophosphate, one of the products of the reaction. Compounds not used as substrate are: GDP, GMP, guanosine, dGTP, ATP, ITP, and XTP. Properties a, b, c, and e (above), as well as the nature of the products, distinguish this enzyme from GTP cyclohydrolase I. Since GTP cyclohydrolase II apparently is not concerned with the biosynthesis of folic acid, the possible physiological role of this enzyme in the biosynthesis of riboflavin is considered in the light of the present investigations and the previously published work on riboflavin biosynthesis by other investigators.", "contents": "Purification and properties of guanosine triphosphate cyclohydrolase II from Escherichia coli. An enzyme that uses GTP as substrate for the formation in stoichiometric quantities of formate, inorganic pyrophosphate, and 2,5-diamino-6-hydroxy-4-(ribosylamino)pyrimidine-5'-phosphate has been purified 2200-fold from extracts of Escherichia coli B. This enzyme is named GTP cyclohydrolase II to distinguish it from a previously studied E. coli enzyme, named GTP cyclohydrolase (and called GTP cyclohydrolase I in this paper), that catalyzes the first of a series of enzymatic reactions leading to the biosynthesis of the pteridine portion of folic acid (Burg, A. W., and Brown, G. M. (1968) J. Biol. Chem. 243, 2349-2358). Some of the properties of GTP cyclohydrolase II are: (a) divalent cations are required for activity (Mg2+ is most effective); (b) its molecular weight, estimated by filtration on Sephadex G-200, is 44,000; (c) the K-m for GTP is 41 mum; (d) its pH optimum is 8.5; and (e) its activity is inhibited by inorganic pyrophosphate, one of the products of the reaction. Compounds not used as substrate are: GDP, GMP, guanosine, dGTP, ATP, ITP, and XTP. Properties a, b, c, and e (above), as well as the nature of the products, distinguish this enzyme from GTP cyclohydrolase I. Since GTP cyclohydrolase II apparently is not concerned with the biosynthesis of folic acid, the possible physiological role of this enzyme in the biosynthesis of riboflavin is considered in the light of the present investigations and the previously published work on riboflavin biosynthesis by other investigators."}
{"id": "PMID:235553", "title": "Carbamyl phosphate: glucose phosphotransferase and glucose-6-phosphate phosphohydrolase of nuclear membrane. Interrelationships between membrane integrity, enzymic latency, and catalytic behavior.", "content": "The presence of carbamyl-phosphate:glucose phosphotransferase in liver nuclei of five species of mammals and birds is demonstrated. The activity is confined to nuclear membranes and is due exclusively to multifunctional glucose-6-phosphatase-phosphotransferase (D-glucose-6-phosphate phosphohydrolase; EC 3.1.3.9). The nuclear enzyme constitutes approximately 16 to 19 percent of total hepatic glucose-6-phosphatase-phosphotransferase. Carbamyl-phosphate:glucose phosphotransferase and glucose-6-P phosphohydrolase activities of membrane of chicken liver nuclei are shown to be catalytically identical with the maximally activated microsomal enzyme. A correspondence is seen in two-substrate kinetic double reciprocal plots, K-m or apparent K-m values for the various substrates, K-i values for the competitive inhibitors P-i and ATP, and pH-activity profiles. Comparative studies were carried out with various intact, disrupted, and detergent-dispersed membranous preparations by a combination of enzyme kinetic and electron microscopic techniques. It is concluded that (a) intimate interrelationships exists between catalytic behavior of this enzyme and morphological integrity of membranes of which the enzyme is a part; (b) activities of the enzyme of nuclear membrane appear quite available for physiological phosphorylative functions; and (c) interrelationships between membrane morphology and catalytic behavior of this membrane-bound enzyme may well be involved in the bioregulation of this complex, multifunctional enzyme system.", "contents": "Carbamyl phosphate: glucose phosphotransferase and glucose-6-phosphate phosphohydrolase of nuclear membrane. Interrelationships between membrane integrity, enzymic latency, and catalytic behavior. The presence of carbamyl-phosphate:glucose phosphotransferase in liver nuclei of five species of mammals and birds is demonstrated. The activity is confined to nuclear membranes and is due exclusively to multifunctional glucose-6-phosphatase-phosphotransferase (D-glucose-6-phosphate phosphohydrolase; EC 3.1.3.9). The nuclear enzyme constitutes approximately 16 to 19 percent of total hepatic glucose-6-phosphatase-phosphotransferase. Carbamyl-phosphate:glucose phosphotransferase and glucose-6-P phosphohydrolase activities of membrane of chicken liver nuclei are shown to be catalytically identical with the maximally activated microsomal enzyme. A correspondence is seen in two-substrate kinetic double reciprocal plots, K-m or apparent K-m values for the various substrates, K-i values for the competitive inhibitors P-i and ATP, and pH-activity profiles. Comparative studies were carried out with various intact, disrupted, and detergent-dispersed membranous preparations by a combination of enzyme kinetic and electron microscopic techniques. It is concluded that (a) intimate interrelationships exists between catalytic behavior of this enzyme and morphological integrity of membranes of which the enzyme is a part; (b) activities of the enzyme of nuclear membrane appear quite available for physiological phosphorylative functions; and (c) interrelationships between membrane morphology and catalytic behavior of this membrane-bound enzyme may well be involved in the bioregulation of this complex, multifunctional enzyme system."}
{"id": "PMID:235554", "title": "Genitourinary anomalies associated with Klippel-Feil syndrome.", "content": "Of thirty-nine patients with Klippel-Feil syndrome, twenty-five (64 per cent) had significant genitourinary-tract anomalies demonstrated by intravenous urogram and physical examination. The incidence of these anomalies in Feil's three types of the syndrome was essentially the same, unilateral renal agenesis being the most common. A routine intravenous urogram is indicated in patients with this syndrome.", "contents": "Genitourinary anomalies associated with Klippel-Feil syndrome. Of thirty-nine patients with Klippel-Feil syndrome, twenty-five (64 per cent) had significant genitourinary-tract anomalies demonstrated by intravenous urogram and physical examination. The incidence of these anomalies in Feil's three types of the syndrome was essentially the same, unilateral renal agenesis being the most common. A routine intravenous urogram is indicated in patients with this syndrome."}
{"id": "PMID:235555", "title": "Cell to substrate adhesion and spreading: inhibition by cationic anesthetics.", "content": "The plasma membrane is the postulated site of action of anesthetics on nerve or muscle. The drugs may be useful in the analysis of membrane phenomena in other cells. We show here that cationic anesthetics and tranquilizers inhibit cell adhesion and spreading, metabolically dependent processes that involve membrane motility and changes in cell shape. Adhesion was measured by layering 51Cr labeled Sarcoma I (Sa I) cells on glass coverslips for 20 minutes at 34 degrees C, rinsing and estimating the glass-associated radioactivity. Spreading was evaluated microscopically. Both cell adhesion to untreated glass and the Mn2+ dependent adhesion to serum-coated coverslips were inhibited by the drugs, in the following order of increasing activity: tetracaine, promethazine, cyclomethycaine, chlorpromazine and fluphenazine. Similar ranks of drug activity have been reported for nerve blocking, inhibition of cell fusion and inhibition of induced spreading of macrophages. Microscopic observations showed the drugs also inhibited MN2+ INDUCED SPREADING OF Sa I. Drug treated cells were rounded, refractile, devoid of cell processes or ruffles visible by light microscopy. The effects of the drugs on adhesion and spreading were reversible upon washing of the cells. We postulate that the inhibition of adhesion and spreading are a consequence of the inhibition of cell surface motility by the anesthetics.", "contents": "Cell to substrate adhesion and spreading: inhibition by cationic anesthetics. The plasma membrane is the postulated site of action of anesthetics on nerve or muscle. The drugs may be useful in the analysis of membrane phenomena in other cells. We show here that cationic anesthetics and tranquilizers inhibit cell adhesion and spreading, metabolically dependent processes that involve membrane motility and changes in cell shape. Adhesion was measured by layering 51Cr labeled Sarcoma I (Sa I) cells on glass coverslips for 20 minutes at 34 degrees C, rinsing and estimating the glass-associated radioactivity. Spreading was evaluated microscopically. Both cell adhesion to untreated glass and the Mn2+ dependent adhesion to serum-coated coverslips were inhibited by the drugs, in the following order of increasing activity: tetracaine, promethazine, cyclomethycaine, chlorpromazine and fluphenazine. Similar ranks of drug activity have been reported for nerve blocking, inhibition of cell fusion and inhibition of induced spreading of macrophages. Microscopic observations showed the drugs also inhibited MN2+ INDUCED SPREADING OF Sa I. Drug treated cells were rounded, refractile, devoid of cell processes or ruffles visible by light microscopy. The effects of the drugs on adhesion and spreading were reversible upon washing of the cells. We postulate that the inhibition of adhesion and spreading are a consequence of the inhibition of cell surface motility by the anesthetics."}
{"id": "PMID:235556", "title": "Reversible alterations in the mitotic cycle of chick embryo cells in various states of growth regulation.", "content": "Chick embryo cells which have been kept overnight at pH 6.8 in the absence of serum multiply very slowly. Only a small fraction of cells is in the S period at any given time, and the rate of uptake of 2-deoxy-D-glucose is very low. Upon raising the pH to 7.4 and adding serum (\"turn-on\") the uptake of 2-deoxy-D-glucose increases immediately; the rate of DNA synthesis increases after a lag of about 4 hours, and represents an increase in the fraction of cells synthesizing DNA. the uptake of 2-deoxy-D-glucose is rapidly returned to its original low rate at any time by again lowering the pH and removing serum (\"turn-off\"). The synthesis of DNA in the culture remains constant or continues to rise at a markedly reduced rate following the same treatment. Lowering pH or removing serum independently of each other is less efficient at inhibiting the increase in DNA synthesis than the combined treatment but each accomplishes a similar result. Cultures which have been \"turned-off\" during the early stages of the rapid increase in DNA synthesis, resume their prior rate of increase immediately if \"turned-on\" again within 2.5 hours. If the cultures have been \"turned-off\" for 5.5 hours before restoring the \"turn-on\", there is a 2 hour delay before they resume an increased rate of DNA synthesis. The results until shortly before, or at the time of the onset of the S period. Up to 96% of the cells in post-confluent cultures growing in conventional medium become labeled upon continuous, prolonged exposure to 3H-thymidine. Seventy-eight percent of the cells in serum-deprived cultures growing at a very low rate become labeled. These and other considerations suggest that the inhibition of cell multiplication by high population density or serum deprivation is caused by a lengthening of the time cells remain in the prereplicative G1 period rather than by shifting cells into a qualitatively distinct G0 period. There may, however, be a period common to all cells regardless of growth rate, in which cells are not progressing toward the S period. The length of this variable period would then determine the growth rate of a population of cells.", "contents": "Reversible alterations in the mitotic cycle of chick embryo cells in various states of growth regulation. Chick embryo cells which have been kept overnight at pH 6.8 in the absence of serum multiply very slowly. Only a small fraction of cells is in the S period at any given time, and the rate of uptake of 2-deoxy-D-glucose is very low. Upon raising the pH to 7.4 and adding serum (\"turn-on\") the uptake of 2-deoxy-D-glucose increases immediately; the rate of DNA synthesis increases after a lag of about 4 hours, and represents an increase in the fraction of cells synthesizing DNA. the uptake of 2-deoxy-D-glucose is rapidly returned to its original low rate at any time by again lowering the pH and removing serum (\"turn-off\"). The synthesis of DNA in the culture remains constant or continues to rise at a markedly reduced rate following the same treatment. Lowering pH or removing serum independently of each other is less efficient at inhibiting the increase in DNA synthesis than the combined treatment but each accomplishes a similar result. Cultures which have been \"turned-off\" during the early stages of the rapid increase in DNA synthesis, resume their prior rate of increase immediately if \"turned-on\" again within 2.5 hours. If the cultures have been \"turned-off\" for 5.5 hours before restoring the \"turn-on\", there is a 2 hour delay before they resume an increased rate of DNA synthesis. The results until shortly before, or at the time of the onset of the S period. Up to 96% of the cells in post-confluent cultures growing in conventional medium become labeled upon continuous, prolonged exposure to 3H-thymidine. Seventy-eight percent of the cells in serum-deprived cultures growing at a very low rate become labeled. These and other considerations suggest that the inhibition of cell multiplication by high population density or serum deprivation is caused by a lengthening of the time cells remain in the prereplicative G1 period rather than by shifting cells into a qualitatively distinct G0 period. There may, however, be a period common to all cells regardless of growth rate, in which cells are not progressing toward the S period. The length of this variable period would then determine the growth rate of a population of cells."}
{"id": "PMID:235557", "title": "Analysis of the induction and deinduction of tyrosine aminotransferase in enucleated HTC cells.", "content": "Anucleate HTC cells have been used to determine the importance of the nucleus in the regulation of the intracellular levels of tyrosine aminotransferase (TAT) in hepatoma tissue culture (HTC) cells. In the absence of the nucleus, neither the induction of the enzyme by dexamethasone nor its deinduction upon removal of the hormone occurs. Degradation of the enzyme takes place when protein synthesis is inhibited in anucleates by cycloheximide. Therefore, the maintenance of induced levels of enzyme activity after dexamethasone withdrawal from pre-induced anucleates suggest that the nucleus is required for the inactivation of the TAT mRNA.", "contents": "Analysis of the induction and deinduction of tyrosine aminotransferase in enucleated HTC cells. Anucleate HTC cells have been used to determine the importance of the nucleus in the regulation of the intracellular levels of tyrosine aminotransferase (TAT) in hepatoma tissue culture (HTC) cells. In the absence of the nucleus, neither the induction of the enzyme by dexamethasone nor its deinduction upon removal of the hormone occurs. Degradation of the enzyme takes place when protein synthesis is inhibited in anucleates by cycloheximide. Therefore, the maintenance of induced levels of enzyme activity after dexamethasone withdrawal from pre-induced anucleates suggest that the nucleus is required for the inactivation of the TAT mRNA."}
{"id": "PMID:235559", "title": "Response of the kallikrein-kinin and renin-angiotensin systems to saline infusion and upright posture.", "content": "The possibility that bradykinin, a potent vasodilator, might be a physiological antagonist of the renin-angiotensin system was investigated. 11 norman subjects, ranging in age from 21 to 33 yr were studied. Seven of the subjects were given a 10 meq sodium, 100 meq potassium, 2500 ml isocaloric diet. After metabolic balance was achieved, they were infused with either 1 liter of 5 per cent glucose over 2 h or 2 liters of 0.9 per cent saline over 4 h. During the infusions, plasma renin activity (PRA), angiotensin II (A II), prekallikrein, bradykinin, and aldosterone levels were frequently determined. Plasma prekallikrein and kallikrein inhibitor did not change during the infusion of either glucose or saline. In subjects receiving saline, plasma bradykinin fell from 3.9 plus or minus 1.5 (SEM) ng/ml at 0 min to 0.93 plus or minus 0.2 at 30 min and 0.95 plus or minus 0.3 at 120 min. These changes paralleled the decrease in PRA over the same period (7.9 plus or minus 1.3 ng/ml/h to 5.6 plus or minus 0.8 at 30 min and 3.5 plus or minus 0.7 at 120 min). Similarly, A II fell from 113 plus or minus 12 pg/ml to 62 plus or minus 10 and 48 plus or minus 5, respectively, at 30 and 120 min. In contrast, the control group infused with glucose showed no change in bradykinin, A II, or PRA. Another four subjects were given a constant 200 meq sodium/100 meq potassium isocaloric diet. After metabolic balance was achieved, they were kept supine and fasting overnight. At 9 a.m. they assumed an upright position and began walking a fixed distance (200 ft) at a normal rate (3-4 ft/s). Plasma prekallikrein and kallikrein inhibitor did not change during the posture study. The plasma bradykinin rose from a base line of 0.54 plus or minus 0.01 (SEM) ng/ml to 0.96 plus or minus 0.13 at 20 min. 0.77 plus or minus 0.18 at 60 min, and 0.96 plus or minus 0.07 at 120 min. These changes parallel the increase in PRA over the same period (1.65 plus or minus 3.3 ng/ml/h to 3.6 plus or minus 0.85 at 20 min, 5.3 plus or minus 0.9 at 60 min, and 5.35 plus or minus 0.55 at 120 min). Likewise, the A II rose from 32.5 plus or minus 1.82 pg/ml to 50.8 plus or minus 3.6 at 20 min, 54.3 plus or minus 3.2 at 60 min, and 61.3 plus or minus 5.9 at 120 min. Thus, in sodium-depleted individuals, saline infusion produces a rapid fall of plasma bradykinin at a rate similar to that observed for a II and PRA. Conversely, in sodium-loaded individuals, assumption of upright posture leads to a parallel rise in A II, TPRA, and bradykinin. These studies indicate that there is a close correlation of bradykinin levels with renin activity and angiotensin II, in both acute sodium loading and assumption of upright posture, suggesting that these two systems may be physiologically interrelated.", "contents": "Response of the kallikrein-kinin and renin-angiotensin systems to saline infusion and upright posture. The possibility that bradykinin, a potent vasodilator, might be a physiological antagonist of the renin-angiotensin system was investigated. 11 norman subjects, ranging in age from 21 to 33 yr were studied. Seven of the subjects were given a 10 meq sodium, 100 meq potassium, 2500 ml isocaloric diet. After metabolic balance was achieved, they were infused with either 1 liter of 5 per cent glucose over 2 h or 2 liters of 0.9 per cent saline over 4 h. During the infusions, plasma renin activity (PRA), angiotensin II (A II), prekallikrein, bradykinin, and aldosterone levels were frequently determined. Plasma prekallikrein and kallikrein inhibitor did not change during the infusion of either glucose or saline. In subjects receiving saline, plasma bradykinin fell from 3.9 plus or minus 1.5 (SEM) ng/ml at 0 min to 0.93 plus or minus 0.2 at 30 min and 0.95 plus or minus 0.3 at 120 min. These changes paralleled the decrease in PRA over the same period (7.9 plus or minus 1.3 ng/ml/h to 5.6 plus or minus 0.8 at 30 min and 3.5 plus or minus 0.7 at 120 min). Similarly, A II fell from 113 plus or minus 12 pg/ml to 62 plus or minus 10 and 48 plus or minus 5, respectively, at 30 and 120 min. In contrast, the control group infused with glucose showed no change in bradykinin, A II, or PRA. Another four subjects were given a constant 200 meq sodium/100 meq potassium isocaloric diet. After metabolic balance was achieved, they were kept supine and fasting overnight. At 9 a.m. they assumed an upright position and began walking a fixed distance (200 ft) at a normal rate (3-4 ft/s). Plasma prekallikrein and kallikrein inhibitor did not change during the posture study. The plasma bradykinin rose from a base line of 0.54 plus or minus 0.01 (SEM) ng/ml to 0.96 plus or minus 0.13 at 20 min. 0.77 plus or minus 0.18 at 60 min, and 0.96 plus or minus 0.07 at 120 min. These changes parallel the increase in PRA over the same period (1.65 plus or minus 3.3 ng/ml/h to 3.6 plus or minus 0.85 at 20 min, 5.3 plus or minus 0.9 at 60 min, and 5.35 plus or minus 0.55 at 120 min). Likewise, the A II rose from 32.5 plus or minus 1.82 pg/ml to 50.8 plus or minus 3.6 at 20 min, 54.3 plus or minus 3.2 at 60 min, and 61.3 plus or minus 5.9 at 120 min. Thus, in sodium-depleted individuals, saline infusion produces a rapid fall of plasma bradykinin at a rate similar to that observed for a II and PRA. Conversely, in sodium-loaded individuals, assumption of upright posture leads to a parallel rise in A II, TPRA, and bradykinin. These studies indicate that there is a close correlation of bradykinin levels with renin activity and angiotensin II, in both acute sodium loading and assumption of upright posture, suggesting that these two systems may be physiologically interrelated."}
{"id": "PMID:235560", "title": "NADPH oxidase deficiency in X-linked chronic granulomatous disease.", "content": "We measured the cyanide-insensitive pyridine nucleotide oxidase activity of fractionated resting and phagocytic neutrophils from 11 normal donors, 1 patient with hereditary deficiency of myeloperoxidase, and 7 patients with X-linked chronic granulomatous disease (CGD). When measured under optimal conditions (at pH 5.5 and in the presence of 0.5 mM Mn++), NADPH oxidase activity increased fourfold with phagocytosis and was six-fold higher than with NADH. Phagocytic neutrophils from patients with CGD were markedly deficient in NADPH oxidase activity.", "contents": "NADPH oxidase deficiency in X-linked chronic granulomatous disease. We measured the cyanide-insensitive pyridine nucleotide oxidase activity of fractionated resting and phagocytic neutrophils from 11 normal donors, 1 patient with hereditary deficiency of myeloperoxidase, and 7 patients with X-linked chronic granulomatous disease (CGD). When measured under optimal conditions (at pH 5.5 and in the presence of 0.5 mM Mn++), NADPH oxidase activity increased fourfold with phagocytosis and was six-fold higher than with NADH. Phagocytic neutrophils from patients with CGD were markedly deficient in NADPH oxidase activity."}
{"id": "PMID:235561", "title": "An isotopic assay for NADPH oxidase activity and some characteristics of the enzyme from human polymorphonuclear leukocytes.", "content": "An isotopic assay for NADPH ixodase that measures the amount of NADP formed by the 6-phosphogluconate dehydrogenase reaction has been developed. Under appropriate conditions, the amount of NADP present is directly proportional to the amount of 14CO2 released from [1-14C]6-phosphogluconic acid. Because this assay employs radioisotopes, it is far more sensitive than conventional assays for the enzyme. The human granule NADPH oxidase, as measured by this assay, is active in the presence of CN minus, is stimulated by Mn-2+, and has a pth optimum of 5.5. Granules isolated from cells that have been allowed to ingest zymosan consistently exhibited more enzyme activity than did granules isolated from either resting cells or cells challenged with zymosan that was not preopsonized. This effect was observed over a wide range of substrate concentrations and could not be explained by differences in protein concentrations between the various samples. If whole homogenates are used in place of isolated granules, the enzyme activity can be observed only with a homogenate of phagocytizing cells and even then only at a high concentration of NADPH. This suggests that an inhibitor of the enzyme might be present within the cell. One patient with chronic granulomatous disease was studied. There was no difference in tnadph oxidase activity of the patients' cells when granules from resting and phagocytizing cells were compared. In contrast, the enzyme activity in granules from two control patients doubled upon phagocytosis. These results are consistent with a role for NADPH oxidase in the initiation of the respiratory burst accompanying phagocytosis by human neutrophils.", "contents": "An isotopic assay for NADPH oxidase activity and some characteristics of the enzyme from human polymorphonuclear leukocytes. An isotopic assay for NADPH ixodase that measures the amount of NADP formed by the 6-phosphogluconate dehydrogenase reaction has been developed. Under appropriate conditions, the amount of NADP present is directly proportional to the amount of 14CO2 released from [1-14C]6-phosphogluconic acid. Because this assay employs radioisotopes, it is far more sensitive than conventional assays for the enzyme. The human granule NADPH oxidase, as measured by this assay, is active in the presence of CN minus, is stimulated by Mn-2+, and has a pth optimum of 5.5. Granules isolated from cells that have been allowed to ingest zymosan consistently exhibited more enzyme activity than did granules isolated from either resting cells or cells challenged with zymosan that was not preopsonized. This effect was observed over a wide range of substrate concentrations and could not be explained by differences in protein concentrations between the various samples. If whole homogenates are used in place of isolated granules, the enzyme activity can be observed only with a homogenate of phagocytizing cells and even then only at a high concentration of NADPH. This suggests that an inhibitor of the enzyme might be present within the cell. One patient with chronic granulomatous disease was studied. There was no difference in tnadph oxidase activity of the patients' cells when granules from resting and phagocytizing cells were compared. In contrast, the enzyme activity in granules from two control patients doubled upon phagocytosis. These results are consistent with a role for NADPH oxidase in the initiation of the respiratory burst accompanying phagocytosis by human neutrophils."}
{"id": "PMID:235562", "title": "Changes in the electroencephalogram in acute uremia. Effects of parathyroid hormone and brain electrolytes.", "content": "Studies were carried out in order to evaluate the effects of changes in brain calcium and the influence of parathyroidectomy and administration of parathyroid extract on the electroencephalogram (EEG) of normal and uremic dogs. Manual analysis of frequency and power distribution of the EEG in uremic dogs revealed a significant increase in both the percentage distribution and the area or power occupied by frequencies below 5 Hz. In addition, high amplitude bursts of delta activity were apparent in the uremic dog. These changes were largely prevented by parathyroidectomy before the induction of uremia, but the administration of parathyroid extract to either normal dogs, or to previously parathyroidectomized uremic dogs, induced EEG changes similar to those noted in uremic animals with intact parathyroid glands. In all groups of animals which showed EEG changes, brain content of calcium was significantly higher than in either normal dogs or previously parathyroidectomized uremic dogs. Changes in arterial pH and bicarbonate, or in the concentrations of Na+, K+, urea, or creatinine in plasma or cerebrospinal fluid were similar in uremic animals with intact parthyroid glands and in previously parathyroidectomized uremia dogs. The results indicate that the EEG changes found in dogs with acute renal failure require the presence of excess parathyroid hormone in blood, and they may be related to the observed changes in brain content of calcium.", "contents": "Changes in the electroencephalogram in acute uremia. Effects of parathyroid hormone and brain electrolytes. Studies were carried out in order to evaluate the effects of changes in brain calcium and the influence of parathyroidectomy and administration of parathyroid extract on the electroencephalogram (EEG) of normal and uremic dogs. Manual analysis of frequency and power distribution of the EEG in uremic dogs revealed a significant increase in both the percentage distribution and the area or power occupied by frequencies below 5 Hz. In addition, high amplitude bursts of delta activity were apparent in the uremic dog. These changes were largely prevented by parathyroidectomy before the induction of uremia, but the administration of parathyroid extract to either normal dogs, or to previously parathyroidectomized uremic dogs, induced EEG changes similar to those noted in uremic animals with intact parathyroid glands. In all groups of animals which showed EEG changes, brain content of calcium was significantly higher than in either normal dogs or previously parathyroidectomized uremic dogs. Changes in arterial pH and bicarbonate, or in the concentrations of Na+, K+, urea, or creatinine in plasma or cerebrospinal fluid were similar in uremic animals with intact parthyroid glands and in previously parathyroidectomized uremia dogs. The results indicate that the EEG changes found in dogs with acute renal failure require the presence of excess parathyroid hormone in blood, and they may be related to the observed changes in brain content of calcium."}
{"id": "PMID:235563", "title": "Ethacrynic acid. Effects on the cochlear potentials in normal and high blood oxygen.", "content": "The effect of ethacrynic acid (EA) at different blood O(2) saturations on cochlear potentials of guinea pigs was investigated. All 18 young healthy guinea pigs received 50 mg/kg/h of EA intravenously and were divided into three groups: first group, normal (90.00+/-6.30-86.17+/-4.83 mm Hg); second group, lower Po(2) (78.00+/-4.74-70.00+/-4.42 mm Hg); and third group, high Po(2) (174.40+/-13.41-179.00+/-26.15 mm Hg). The partial pressure of oxygen (Po(2)), the partial pressure of carbon dioxide (Pco(2)), and the pH of the blood were measured before EA administration and at the end of the experiment (3 h later) by drawing blood samples from the contralateral carotid artery. Cochlear potentials-endocochlear potential (EP), cochlear microphonics (CM), and action potentials (AP)-were recorded by standard methods from the first turn of the cochlea. Experimental data seem to indicate that elevation of the Po(2) to 174-179 mm Hg during relatively high doses of EA treatment prevents the declines in cochlear potentials which were observed in the first and second groups (normal and lower Po(2)), and preserves active ion transport which is responsible for the generation of cochlear potentials. These data suggest a means by which to reduce the ototoxic effect of EA and possibly indicates a method of treatment for hearing loss which developed after the administration of EA.", "contents": "Ethacrynic acid. Effects on the cochlear potentials in normal and high blood oxygen. The effect of ethacrynic acid (EA) at different blood O(2) saturations on cochlear potentials of guinea pigs was investigated. All 18 young healthy guinea pigs received 50 mg/kg/h of EA intravenously and were divided into three groups: first group, normal (90.00+/-6.30-86.17+/-4.83 mm Hg); second group, lower Po(2) (78.00+/-4.74-70.00+/-4.42 mm Hg); and third group, high Po(2) (174.40+/-13.41-179.00+/-26.15 mm Hg). The partial pressure of oxygen (Po(2)), the partial pressure of carbon dioxide (Pco(2)), and the pH of the blood were measured before EA administration and at the end of the experiment (3 h later) by drawing blood samples from the contralateral carotid artery. Cochlear potentials-endocochlear potential (EP), cochlear microphonics (CM), and action potentials (AP)-were recorded by standard methods from the first turn of the cochlea. Experimental data seem to indicate that elevation of the Po(2) to 174-179 mm Hg during relatively high doses of EA treatment prevents the declines in cochlear potentials which were observed in the first and second groups (normal and lower Po(2)), and preserves active ion transport which is responsible for the generation of cochlear potentials. These data suggest a means by which to reduce the ototoxic effect of EA and possibly indicates a method of treatment for hearing loss which developed after the administration of EA."}
{"id": "PMID:235564", "title": "Red cell NADP+ and NADPH in glucose-6-phosphate dehydrogenase deficiency.", "content": "Extraction in the presence of sodium hydroxide and cysteine allows estimates of NADPH and total NADP in human red cells without the erroneously high values of NADP+ obtained with earlier methods. An application of this technique to G6PD-deficient cells reveals that most of the nucleotide is in the oxidized form. In contrast, normal red cells have nearly all of the nucleotide in the reudced form. In addition to providing information concerning the intracellular regulation of the hexose monophosphate shunt, these findings support the concept that G6PD deficiency is a product-deficiency disorder.", "contents": "Red cell NADP+ and NADPH in glucose-6-phosphate dehydrogenase deficiency. Extraction in the presence of sodium hydroxide and cysteine allows estimates of NADPH and total NADP in human red cells without the erroneously high values of NADP+ obtained with earlier methods. An application of this technique to G6PD-deficient cells reveals that most of the nucleotide is in the oxidized form. In contrast, normal red cells have nearly all of the nucleotide in the reudced form. In addition to providing information concerning the intracellular regulation of the hexose monophosphate shunt, these findings support the concept that G6PD deficiency is a product-deficiency disorder."}
{"id": "PMID:235565", "title": "Energy dependence of urinary bicarbonate secretion in turtle bladder.", "content": "Addition of HCO3- to the serosal side (S) of the isolated turtle bladder results in a HCO3- flow from S to the mucosal side (M) which markedly reduces the net rate of acid secretion. To characterize the driving forces for this downhill HCO3- flow, the effects of metabolic inhibitors and substrates were examined. In short-circuited bladders with the M pH lowered  to the point of zero net H+ secretion, the rate of HCO3- entry into M in response to a 20-mM HCO3- gradient was measured by pH stat titration. Deoxygenation reduced the HCO3- flux from 1.24 plus or minus 0.1 mum/h/8 cm2 (SEM) to 0.50 plus or minus 0.1 muM/h with glucose (2 times 10-3 M) AND FROM 1.32 PLUS OR MINUS TO 0.47 PLUS OR MINUS 0.1 MUM/h without glucose. A similar reduction (61 per cent) was observed in the presence of 1 per cent C92. Dinitrophenol (10-4 M), cyanide (10-3 M), and deoxyglucose (10-2 M) inhibited the HCO3- flux by 39 per cent, 37 per cent, and 38 per cent, respectively. The combination of any of these inhibitors with N2 caused the same inhibition as N2 alone. In bladders depleted of substrate, pyruvate (5 times 10-3 M) increased the HCO3- flux from 0.36 plus or minus 0.05 to 0.58 plus or minus 0.01 muM/h (P smaller than 0.005); the increment was abolished by deoxygenation. The results indicate that the bulk of the downhill HCO3- flow in this system is dependent on metabolic energy derived primarily from oxidative sources, and that this energy-dependent flow approximates the electroneutral component of HCO3- secretion that is coupled to Cl- absorption.", "contents": "Energy dependence of urinary bicarbonate secretion in turtle bladder. Addition of HCO3- to the serosal side (S) of the isolated turtle bladder results in a HCO3- flow from S to the mucosal side (M) which markedly reduces the net rate of acid secretion. To characterize the driving forces for this downhill HCO3- flow, the effects of metabolic inhibitors and substrates were examined. In short-circuited bladders with the M pH lowered  to the point of zero net H+ secretion, the rate of HCO3- entry into M in response to a 20-mM HCO3- gradient was measured by pH stat titration. Deoxygenation reduced the HCO3- flux from 1.24 plus or minus 0.1 mum/h/8 cm2 (SEM) to 0.50 plus or minus 0.1 muM/h with glucose (2 times 10-3 M) AND FROM 1.32 PLUS OR MINUS TO 0.47 PLUS OR MINUS 0.1 MUM/h without glucose. A similar reduction (61 per cent) was observed in the presence of 1 per cent C92. Dinitrophenol (10-4 M), cyanide (10-3 M), and deoxyglucose (10-2 M) inhibited the HCO3- flux by 39 per cent, 37 per cent, and 38 per cent, respectively. The combination of any of these inhibitors with N2 caused the same inhibition as N2 alone. In bladders depleted of substrate, pyruvate (5 times 10-3 M) increased the HCO3- flux from 0.36 plus or minus 0.05 to 0.58 plus or minus 0.01 muM/h (P smaller than 0.005); the increment was abolished by deoxygenation. The results indicate that the bulk of the downhill HCO3- flow in this system is dependent on metabolic energy derived primarily from oxidative sources, and that this energy-dependent flow approximates the electroneutral component of HCO3- secretion that is coupled to Cl- absorption."}
{"id": "PMID:235566", "title": "Guanosine 3',5'-monophosphate and adenosine 3',5'-monophosphate content of human umbilical artery.", "content": "Human umbilical arteries are unique vessels in that they close quickly and completely at birth. It has been suggested that cyclic uanosine 3',5'-monophosphate (cAMP) in relaxation. This hypothesis has been evaluated in term gestational human umbilical artery segments incubated at 37 degrees C and in room air. (a) The basal cGMP content (1 pmol/mg protein) of artery segments incubated in room air was almost twice that of cAMP. (b) Bradykinin, histamine, serotonin, acetylcholine, and K+ ion, which cause umbilical artery constriction, can increase the cGMP content of the artery segments within 30 s of exposure without altering the cAMP content. (c) Prostaglandin E1, but not isoproterenol, caused accumulation of cAMP which is consistent with reports that umbilical arteries lack functional beta-receptors and that only prostaglandin E1 can bring about relaxation of umbilical arteries. (d) 1 muM atropine blocked the effect of 100 muM acetylcholine on cGMP content without altering the responses to histamine, bradykinin, serotonin, or K+ ion. (e) Pyrilamine (an H1 antagonist), but not metiamide (an H2 antagonist), blocked the effect of histamine on cGMP from which it is inferred that histamine causes accumulation of cGMP in umbilical artery via its interaction with H1 receptors. The results are consistent with the view that metabolism of the two cyclic nucleotides is independently controlled in the human umbilical artery and that cGMP is involved in contraction of the artery at birth.", "contents": "Guanosine 3',5'-monophosphate and adenosine 3',5'-monophosphate content of human umbilical artery. Human umbilical arteries are unique vessels in that they close quickly and completely at birth. It has been suggested that cyclic uanosine 3',5'-monophosphate (cAMP) in relaxation. This hypothesis has been evaluated in term gestational human umbilical artery segments incubated at 37 degrees C and in room air. (a) The basal cGMP content (1 pmol/mg protein) of artery segments incubated in room air was almost twice that of cAMP. (b) Bradykinin, histamine, serotonin, acetylcholine, and K+ ion, which cause umbilical artery constriction, can increase the cGMP content of the artery segments within 30 s of exposure without altering the cAMP content. (c) Prostaglandin E1, but not isoproterenol, caused accumulation of cAMP which is consistent with reports that umbilical arteries lack functional beta-receptors and that only prostaglandin E1 can bring about relaxation of umbilical arteries. (d) 1 muM atropine blocked the effect of 100 muM acetylcholine on cGMP content without altering the responses to histamine, bradykinin, serotonin, or K+ ion. (e) Pyrilamine (an H1 antagonist), but not metiamide (an H2 antagonist), blocked the effect of histamine on cGMP from which it is inferred that histamine causes accumulation of cGMP in umbilical artery via its interaction with H1 receptors. The results are consistent with the view that metabolism of the two cyclic nucleotides is independently controlled in the human umbilical artery and that cGMP is involved in contraction of the artery at birth."}
{"id": "PMID:235567", "title": "In vivo myocardial cell pH in the dog. Response to ischemia and infusion of alkali.", "content": "Myocardial cell pH has been measured with 5,5-dimethyl-2,4-oxazolidinedione (DMO) in intact anesthetized dogs by a transient indicator dilution technique. Bolus injections of labeled DMO, vascular, extracellular, and water indicators were made into the anterior descending coronary artery, and blood samples were collected from the great cardiac vein. The steady-state distribution of DMO between cells and plasma was calculated from the indicator mean transit times, and the plasma pH. Myocardial cell pH was determined from the distribution value and plasma pH. Normal myocardial cell pH averaged 6.94. Changes in myocardial cell pH after infusions of acid or alkali. Myocardial ischemia induced by inflation of a coronary artery balloon resulted in progressive decreases in cellular pH to average values of 6.83 within the initial 15 min and to 6.59 within the interval between 20 and 70 min. Infusions of Na2CO3 tended to diminish intracellular acidosis although these infusions had little effect on the difference in pH between the myocardial cell and extracellular fluid.", "contents": "In vivo myocardial cell pH in the dog. Response to ischemia and infusion of alkali. Myocardial cell pH has been measured with 5,5-dimethyl-2,4-oxazolidinedione (DMO) in intact anesthetized dogs by a transient indicator dilution technique. Bolus injections of labeled DMO, vascular, extracellular, and water indicators were made into the anterior descending coronary artery, and blood samples were collected from the great cardiac vein. The steady-state distribution of DMO between cells and plasma was calculated from the indicator mean transit times, and the plasma pH. Myocardial cell pH was determined from the distribution value and plasma pH. Normal myocardial cell pH averaged 6.94. Changes in myocardial cell pH after infusions of acid or alkali. Myocardial ischemia induced by inflation of a coronary artery balloon resulted in progressive decreases in cellular pH to average values of 6.83 within the initial 15 min and to 6.59 within the interval between 20 and 70 min. Infusions of Na2CO3 tended to diminish intracellular acidosis although these infusions had little effect on the difference in pH between the myocardial cell and extracellular fluid."}
{"id": "PMID:235568", "title": "Pharyngeal lipase and digestion of dietary triglyceride in man.", "content": "Lipolytic activity was studied in esophageal and gastric aspirates obtained with a nasogastric tube from 14 healthy adult subjects. Samples were collected from esophagus, first at 30-35 cm and then at 40-45 cm from the nose, as the subject, after drinking 15-30 ml of a cream-milk mixture, swallowed small amounts of water. The samples from stomach were taken last and usually contained a small amount of cream-milk mixture. Lipolytic activity was assayed using chylomicron, milk, and corn oil triglyceride as substrate. Esophageal and gastric samples both contained lipolytic activity which hydrolyzed long-chain triglyceride to diglyceride, monoglyceride, and FFTA, had a pH optimum of 5.4, and was not affected by either had a pH optimum of 5.4, and was not affected by either 0.5 M NaCl or 4 mM sodium taurodexycholate. The activity, expressed as nanomoles of chylomicron triglyceride hydrolyzed per milliter per minute, ranged from 0 to 145 in upper esophageal, 5 to 303 in lower esophageal, and 50 to 357 in gastric samples. Only a trace of lipolytic activity was found at pH 5.4 in saliva collected from the parotid, submandibular, and sublingual glands, thus excluding those tissues as a source of the activity found in esophageal and gastric aspirates. The findings suggest that in man glands in or near the pharynx secrete a lipase that acts in the stomach to hydrolyze long-chain triglyceride to partial glycerides and FFA. It is proposed this reaction is the first step in the digestion of dietary fat and that the amphiphilic lipids formed by lipolysis facilitate the emulsification of triglyceride in the stomach.", "contents": "Pharyngeal lipase and digestion of dietary triglyceride in man. Lipolytic activity was studied in esophageal and gastric aspirates obtained with a nasogastric tube from 14 healthy adult subjects. Samples were collected from esophagus, first at 30-35 cm and then at 40-45 cm from the nose, as the subject, after drinking 15-30 ml of a cream-milk mixture, swallowed small amounts of water. The samples from stomach were taken last and usually contained a small amount of cream-milk mixture. Lipolytic activity was assayed using chylomicron, milk, and corn oil triglyceride as substrate. Esophageal and gastric samples both contained lipolytic activity which hydrolyzed long-chain triglyceride to diglyceride, monoglyceride, and FFTA, had a pH optimum of 5.4, and was not affected by either had a pH optimum of 5.4, and was not affected by either 0.5 M NaCl or 4 mM sodium taurodexycholate. The activity, expressed as nanomoles of chylomicron triglyceride hydrolyzed per milliter per minute, ranged from 0 to 145 in upper esophageal, 5 to 303 in lower esophageal, and 50 to 357 in gastric samples. Only a trace of lipolytic activity was found at pH 5.4 in saliva collected from the parotid, submandibular, and sublingual glands, thus excluding those tissues as a source of the activity found in esophageal and gastric aspirates. The findings suggest that in man glands in or near the pharynx secrete a lipase that acts in the stomach to hydrolyze long-chain triglyceride to partial glycerides and FFA. It is proposed this reaction is the first step in the digestion of dietary fat and that the amphiphilic lipids formed by lipolysis facilitate the emulsification of triglyceride in the stomach."}
{"id": "PMID:235569", "title": "The influence of extraneous factors on Coulter S measurement of the mean corpuscular volume.", "content": "Alteration in the temperature of the Isoton diluent in a Coulter model S counter over a range of possible laboratory working temperatures produced a change in the mean corpuscular volume using EDTA and dipotassium acid citrate dextrose blood and a commercial control, 4C. Contamination of the Isoton diluent with hypochlorite solution, used to clean the Coulter model S, may increase the mean corpuscular volume of EDTA blood without altering other measured parameters. Attention to both these points is required in assessing quality and calibrating the machine.", "contents": "The influence of extraneous factors on Coulter S measurement of the mean corpuscular volume. Alteration in the temperature of the Isoton diluent in a Coulter model S counter over a range of possible laboratory working temperatures produced a change in the mean corpuscular volume using EDTA and dipotassium acid citrate dextrose blood and a commercial control, 4C. Contamination of the Isoton diluent with hypochlorite solution, used to clean the Coulter model S, may increase the mean corpuscular volume of EDTA blood without altering other measured parameters. Attention to both these points is required in assessing quality and calibrating the machine."}
{"id": "PMID:235570", "title": "The Compu-pet 100: a versatile dispenser-diluter for the mechanization of microbiological techniques.", "content": "The Compu-pet 100 diluter/dispenser is a versatile and accurate instrument which can be employed for a wide variety of microbiological tests and techniques. Time in performing tests is often more than halved when the diluter is used. Large numbers of tests can be performed with minimal fatigue.", "contents": "The Compu-pet 100: a versatile dispenser-diluter for the mechanization of microbiological techniques. The Compu-pet 100 diluter/dispenser is a versatile and accurate instrument which can be employed for a wide variety of microbiological tests and techniques. Time in performing tests is often more than halved when the diluter is used. Large numbers of tests can be performed with minimal fatigue."}
{"id": "PMID:235571", "title": "Neocortical and hippocampal activation relation to behavior: effects of atropine, eserine, phenothiazines, and amphetamine.", "content": "Evidence is presented to suggest that the hippocampus receives 2 nonspecific inputs from the brainstem, each capable of producing rhythmical slow activity. The neocortex appears to receive 2 similar inputs, each capable of producing low voltage fast activity. One input to both hippocampus and neocortex is blocked by atropine and stimulated by eserine, and is essentially unrelated to concurrent motor activity. A second input to both hippocampus and neocortex is resistant to atropine, is depressed by phenothiazines, and is activated by d-amphetamine. Activity in this system is closely related to concurrent \"voluntary\" movement.", "contents": "Neocortical and hippocampal activation relation to behavior: effects of atropine, eserine, phenothiazines, and amphetamine. Evidence is presented to suggest that the hippocampus receives 2 nonspecific inputs from the brainstem, each capable of producing rhythmical slow activity. The neocortex appears to receive 2 similar inputs, each capable of producing low voltage fast activity. One input to both hippocampus and neocortex is blocked by atropine and stimulated by eserine, and is essentially unrelated to concurrent motor activity. A second input to both hippocampus and neocortex is resistant to atropine, is depressed by phenothiazines, and is activated by d-amphetamine. Activity in this system is closely related to concurrent \"voluntary\" movement."}
{"id": "PMID:235572", "title": "Role of the biogenic amines in the reversal of cycloheximide-induced amnesia.", "content": "Amnesia was induced by pretraining injections of cycloheximide (CYC) in a food motivated discrimination reversal task. Magnitude of amnesia varied as a function of the amount of training on both the initial discrimination and the reversal and also as a function of the length of intertrial interval used on both the reversal and the test. Memory spontaneously recovered 48 hr. following reversal training. Recovery from amnesia was induced by pretesting injections of d-amphetamine and 2 monoamine oxidase inhibitors, pargyline and catron. This enhanced performance was a true recovery of the memory and  not a result of enhanced learning or increased arousal. Depletion of catecholamines by alpha-methyl-para-tyrosine, a tyrosine hydroxylase inhibitor, and diethyldithiocarbamate, a dopamine beta hydroxylase inhbitor, resulted in an amnesia quantitatively and qualitatively similar to amnesia induced by CYC. These data support the hypothesis that CYC-induced amnesia is mediated via central catecholamines.", "contents": "Role of the biogenic amines in the reversal of cycloheximide-induced amnesia. Amnesia was induced by pretraining injections of cycloheximide (CYC) in a food motivated discrimination reversal task. Magnitude of amnesia varied as a function of the amount of training on both the initial discrimination and the reversal and also as a function of the length of intertrial interval used on both the reversal and the test. Memory spontaneously recovered 48 hr. following reversal training. Recovery from amnesia was induced by pretesting injections of d-amphetamine and 2 monoamine oxidase inhibitors, pargyline and catron. This enhanced performance was a true recovery of the memory and  not a result of enhanced learning or increased arousal. Depletion of catecholamines by alpha-methyl-para-tyrosine, a tyrosine hydroxylase inhibitor, and diethyldithiocarbamate, a dopamine beta hydroxylase inhbitor, resulted in an amnesia quantitatively and qualitatively similar to amnesia induced by CYC. These data support the hypothesis that CYC-induced amnesia is mediated via central catecholamines."}
{"id": "PMID:235573", "title": "Monoaminergic mediation of female sexual behavior.", "content": "Lordotic behavior was facilitated in estrogen-primed female rats by direct application of progesterone or serotonergic or beta-adrenergic receptor blockers to specific telencephalic, anterior hypothalamic-medial preoptic, or posterior hypothalamic sites. Blockade of the alpha-adrenergic system was ineffective in facilitating lordosis, as was the application of the active drugs to control sites in the thalamus or basal ganglia. Female soliciting behavior was not evoked by any of the treatments. It is concluded that the lordotic behavior component of the female rat's estrous behavior pattern is inhibited by a specific central monoaminergic system that also responds to progesterone. Soliciting behavior appears to be mediated by systems that are anatomically, and possibly neurochemically, separable from those regulating lordosis.", "contents": "Monoaminergic mediation of female sexual behavior. Lordotic behavior was facilitated in estrogen-primed female rats by direct application of progesterone or serotonergic or beta-adrenergic receptor blockers to specific telencephalic, anterior hypothalamic-medial preoptic, or posterior hypothalamic sites. Blockade of the alpha-adrenergic system was ineffective in facilitating lordosis, as was the application of the active drugs to control sites in the thalamus or basal ganglia. Female soliciting behavior was not evoked by any of the treatments. It is concluded that the lordotic behavior component of the female rat's estrous behavior pattern is inhibited by a specific central monoaminergic system that also responds to progesterone. Soliciting behavior appears to be mediated by systems that are anatomically, and possibly neurochemically, separable from those regulating lordosis."}
{"id": "PMID:235574", "title": "Female lordotic behavior mediated by monoamines in male rats.", "content": "Direct application of serotonergic of beta-adrenergic receptor blockers to anterior or posterior areas of the hypothalamus induced lordosis in intact estrogen-primed male rats. Such treatment with an alpha-adrenergic blocker or systemic administration of progesterone failed to increase lordosis. Centrally elicited lordosis did not occur without estrogen priming. Anatomical and neurochemical similarity may exist in the brain mechanism mediating lordotic behavior in male and female adult rats.", "contents": "Female lordotic behavior mediated by monoamines in male rats. Direct application of serotonergic of beta-adrenergic receptor blockers to anterior or posterior areas of the hypothalamus induced lordosis in intact estrogen-primed male rats. Such treatment with an alpha-adrenergic blocker or systemic administration of progesterone failed to increase lordosis. Centrally elicited lordosis did not occur without estrogen priming. Anatomical and neurochemical similarity may exist in the brain mechanism mediating lordotic behavior in male and female adult rats."}
{"id": "PMID:235576", "title": "The nature of the stimulation of the growth of Streptococcus lactis by yeast extract.", "content": "Yeast extract was fractionated on Sephadex G-25 into 7 fractions. The fraction most stimulatory to the growth of Streptococcus lactis C10 contained over 70% of the amino N present in yeast extract and consisted of a wide variety of free amino acids and a small amount of peptide material. Examination of possible replacement factors for this fraction revealed that the amino -acid material present was largely responsible for the stimulation of Str. lactis C10. Purine and pyrimidine bases and inorganic constituents also contributed to the stimulation. In addition, yeast extract contained a component which decomposed H2O2, a metabolite which accumulates in the growth medium under aerobic conditions and inhibits growth. The nature of the stimulation was studied by isolating slow and fast acid-producing colonies of Str. lactis C10. It appeared that yeast extract and other amino-acid supplements prevented an observed inhibition of the growth of the slow variants below pH 6.0, apparently by satisfying a nutritional deficiency caused by a drop in pH.", "contents": "The nature of the stimulation of the growth of Streptococcus lactis by yeast extract. Yeast extract was fractionated on Sephadex G-25 into 7 fractions. The fraction most stimulatory to the growth of Streptococcus lactis C10 contained over 70% of the amino N present in yeast extract and consisted of a wide variety of free amino acids and a small amount of peptide material. Examination of possible replacement factors for this fraction revealed that the amino -acid material present was largely responsible for the stimulation of Str. lactis C10. Purine and pyrimidine bases and inorganic constituents also contributed to the stimulation. In addition, yeast extract contained a component which decomposed H2O2, a metabolite which accumulates in the growth medium under aerobic conditions and inhibits growth. The nature of the stimulation was studied by isolating slow and fast acid-producing colonies of Str. lactis C10. It appeared that yeast extract and other amino-acid supplements prevented an observed inhibition of the growth of the slow variants below pH 6.0, apparently by satisfying a nutritional deficiency caused by a drop in pH."}
{"id": "PMID:235577", "title": "Pptidase activities in group N streptococci.", "content": "Several peptidase activites in the 3 species of Group N streptococci were partly separated by gel filtration on Sephadex G-200. The peptidases identified were a general aminopeptidase of wide specificity, a tripeptidase, a proline iminopeptidase (prolyl-beta-napthylamidase), a proline iminodipeptidase and an aminopeptidase-P. The effects of temperature and pH on the stability of the enzyme activities, and the influence of the type of N source used in the growth medium on the elution pattern of the enzymes were examined.", "contents": "Pptidase activities in group N streptococci. Several peptidase activites in the 3 species of Group N streptococci were partly separated by gel filtration on Sephadex G-200. The peptidases identified were a general aminopeptidase of wide specificity, a tripeptidase, a proline iminopeptidase (prolyl-beta-napthylamidase), a proline iminodipeptidase and an aminopeptidase-P. The effects of temperature and pH on the stability of the enzyme activities, and the influence of the type of N source used in the growth medium on the elution pattern of the enzymes were examined."}
{"id": "PMID:235578", "title": "Preparation and properties of beta-casein from buffalo's milk.", "content": "Beta-casein from individual buffalo's milk was found to be homogeneous by starch-gel electrophoresis. Beta-Casein was separated from buffalo's milk by the method of Warner (1944) and purified by DEAE-cellulose chromatography. Buffalo beta-casein possesses identical end-groups to those of cow beta-casein; namely N-terminal arginine and assuming a single polypeptide chain a possible C-terminal sequence of Ile-Ile-Val. However, the amino-acid composition and the trypic peptide patterns of the 2 proteins are not the same.", "contents": "Preparation and properties of beta-casein from buffalo's milk. Beta-casein from individual buffalo's milk was found to be homogeneous by starch-gel electrophoresis. Beta-Casein was separated from buffalo's milk by the method of Warner (1944) and purified by DEAE-cellulose chromatography. Buffalo beta-casein possesses identical end-groups to those of cow beta-casein; namely N-terminal arginine and assuming a single polypeptide chain a possible C-terminal sequence of Ile-Ile-Val. However, the amino-acid composition and the trypic peptide patterns of the 2 proteins are not the same."}
{"id": "PMID:235584", "title": "The effect of aging and acute illness on delayed hypersensitivity.", "content": "A group of standard antigens (monilia, mosquito, mumps, purified protein derivative [PPD], staphylococcus toxoid, streptokinase-streptodornase [sk-sd] and trichophyton) were applied to 321 normal volunteers, 60 patients admitted to a medical ward, and 41 patients in an intensive care unit (ICU) to evaluate their delayed hypersensitivity skin test response. Eighty-eight per cent of the normal subjects reacted with at least 5 mm. induration to one or more skin tests without any decrease in reactivity occurring with increasing age. In the hospitalized group, only 62 per cent of the ward and 63 per cent of the ICU patients reacted to the same skin tests. All (8/8) anergic ICU patients tested after discharge regained normal reactivity. Acute illness but not increasing age will impair the delayed hypersensitivity skin test response.", "contents": "The effect of aging and acute illness on delayed hypersensitivity. A group of standard antigens (monilia, mosquito, mumps, purified protein derivative [PPD], staphylococcus toxoid, streptokinase-streptodornase [sk-sd] and trichophyton) were applied to 321 normal volunteers, 60 patients admitted to a medical ward, and 41 patients in an intensive care unit (ICU) to evaluate their delayed hypersensitivity skin test response. Eighty-eight per cent of the normal subjects reacted with at least 5 mm. induration to one or more skin tests without any decrease in reactivity occurring with increasing age. In the hospitalized group, only 62 per cent of the ward and 63 per cent of the ICU patients reacted to the same skin tests. All (8/8) anergic ICU patients tested after discharge regained normal reactivity. Acute illness but not increasing age will impair the delayed hypersensitivity skin test response."}
{"id": "PMID:235589", "title": "Inactivation of slow reacting substance of anaphylaxis by human eosinophil arylsulfatase.", "content": "Arylsulfatase preferentially present in the human eosinophil as compared to other leukocytes was isolated by sequential gel filtration and cation exchange chromatography. The apparent molecular weight of 60,000, the preferential cleavage of 4-nitrocatechol sulfate (PNCS) over p-acetyl-benzenesulfonic acid (PABS), inhibition by phosphate ions and pH optimum of 5.7 are characteristics of a type II B arylsulfatase. Eosinophil arylsulfatase inactivated purified human slow reacting substance of anaphylaxis (SRS-A) in a time-dependent reaction with the rate dependent upon the enzyme/substrate ratio. That SRS-A inactivation was the result of intrinsic arylsulfatase activity was indicated by association of PNCS cleavage and SRS-A inactivating activity during chromatography, the similar pH optimum for cleavage of both substrates and the capacity of SRS-A to inhibit PNCS cleavage by arylsulfatase. The finding that eosinophil arylsulfatase inactivates SRS-A suggests that eosinophil ingress into the site of an immediate hypersensitivity reaction in response to ECF-A could represent a regulatory function.", "contents": "Inactivation of slow reacting substance of anaphylaxis by human eosinophil arylsulfatase. Arylsulfatase preferentially present in the human eosinophil as compared to other leukocytes was isolated by sequential gel filtration and cation exchange chromatography. The apparent molecular weight of 60,000, the preferential cleavage of 4-nitrocatechol sulfate (PNCS) over p-acetyl-benzenesulfonic acid (PABS), inhibition by phosphate ions and pH optimum of 5.7 are characteristics of a type II B arylsulfatase. Eosinophil arylsulfatase inactivated purified human slow reacting substance of anaphylaxis (SRS-A) in a time-dependent reaction with the rate dependent upon the enzyme/substrate ratio. That SRS-A inactivation was the result of intrinsic arylsulfatase activity was indicated by association of PNCS cleavage and SRS-A inactivating activity during chromatography, the similar pH optimum for cleavage of both substrates and the capacity of SRS-A to inhibit PNCS cleavage by arylsulfatase. The finding that eosinophil arylsulfatase inactivates SRS-A suggests that eosinophil ingress into the site of an immediate hypersensitivity reaction in response to ECF-A could represent a regulatory function."}
{"id": "PMID:235591", "title": "Metabolism of glucose and fatty acid by leukocytes from patients with endogenous hypertriglyceridemia.", "content": "The metabolic abnormalities responsible for endogenous hypertriglyceridemia have not been defined. Some in vivo studies have suggested that excessive triglyceride production is the cause of this defect. In an attempt to obtain direct evidence concerning this mechanism, we have compared in vitro the metabolism of radioactive glucose and palmitate by leukocytes from patients with endogenous hypertriglyceridemia and normal subjects. Leukocytes from the patients incorporated 9.82 plus or minus 1.7 (S.E.M.) nanomoles of glucose into cellular lipid per 10-8 cells per hour. When the cell lipid extract was sugjected to mild alkaline hydrolysis, 92 per cent of the glucose radioactivity was recovered in the glycerol backbone of the lipid esters. Comparison of specific yields of CO2 from glucose labeled in the 1- or 6- position revealed that 0.53 plus or minus 0.02 per cent was metabolized via the pentose cycle. The leukocytes from hypertriglyceridemic persons incorproated 140 plus or minus 6.9 nanomoles of [1-14C]-palmitate per 10-8 cells per hour. Eighty-four per cent of the radioactivity was in triglycerides and 14 per cent in phospholipids. The major phospholipid into which palmitate was incorporated was phosphatidyl choline. The leukocytes oxidized palmitate at a rate of 2.88 plus or minus 0.23 nanomoles per 10-8 cells per hour. There were no differences in any of the above values between leukocytes from hypertriglyceridemic patients and normal subjects. Likewise, there was no correlation between the plasma triglyceride concentration and glucose or palmitate incorporation into triglycerides. To the extent that leukocytes reflect systemic metabolic processes, these data provide no support for the interpretation that the mechanism of the plasma triglyceride elevation is excessive biosynthesis.", "contents": "Metabolism of glucose and fatty acid by leukocytes from patients with endogenous hypertriglyceridemia. The metabolic abnormalities responsible for endogenous hypertriglyceridemia have not been defined. Some in vivo studies have suggested that excessive triglyceride production is the cause of this defect. In an attempt to obtain direct evidence concerning this mechanism, we have compared in vitro the metabolism of radioactive glucose and palmitate by leukocytes from patients with endogenous hypertriglyceridemia and normal subjects. Leukocytes from the patients incorporated 9.82 plus or minus 1.7 (S.E.M.) nanomoles of glucose into cellular lipid per 10-8 cells per hour. When the cell lipid extract was sugjected to mild alkaline hydrolysis, 92 per cent of the glucose radioactivity was recovered in the glycerol backbone of the lipid esters. Comparison of specific yields of CO2 from glucose labeled in the 1- or 6- position revealed that 0.53 plus or minus 0.02 per cent was metabolized via the pentose cycle. The leukocytes from hypertriglyceridemic persons incorproated 140 plus or minus 6.9 nanomoles of [1-14C]-palmitate per 10-8 cells per hour. Eighty-four per cent of the radioactivity was in triglycerides and 14 per cent in phospholipids. The major phospholipid into which palmitate was incorporated was phosphatidyl choline. The leukocytes oxidized palmitate at a rate of 2.88 plus or minus 0.23 nanomoles per 10-8 cells per hour. There were no differences in any of the above values between leukocytes from hypertriglyceridemic patients and normal subjects. Likewise, there was no correlation between the plasma triglyceride concentration and glucose or palmitate incorporation into triglycerides. To the extent that leukocytes reflect systemic metabolic processes, these data provide no support for the interpretation that the mechanism of the plasma triglyceride elevation is excessive biosynthesis."}
{"id": "PMID:235592", "title": "The sorbitol-oxidizing enzyme of red blood cells.", "content": "The sorbitol-oxidizing enzyme of human erythrocytes has been partially purified and characterized. Its kinetic characteristics were found to be similar to the sorbitol dehydrogenase of sheep liver and the DPN-xyluloxe dehydrogenase which have been isolated from sheep liver and guinea pig liver, respectively. Although this enzyme is able to oxidize sorbitol relatively efficiently, it has very little activity toward dulcitol, and therefore cannot account for the high K-m pathway of methemoglobin reduction by galactose.", "contents": "The sorbitol-oxidizing enzyme of red blood cells. The sorbitol-oxidizing enzyme of human erythrocytes has been partially purified and characterized. Its kinetic characteristics were found to be similar to the sorbitol dehydrogenase of sheep liver and the DPN-xyluloxe dehydrogenase which have been isolated from sheep liver and guinea pig liver, respectively. Although this enzyme is able to oxidize sorbitol relatively efficiently, it has very little activity toward dulcitol, and therefore cannot account for the high K-m pathway of methemoglobin reduction by galactose."}
{"id": "PMID:235593", "title": "Erythrocyte delta-aminolevulinic acid dehydratase activity as a measure of lead exposure.", "content": "The measurement of erythrocyte delta-aminolevulinic acid dehydratase (ALA-D) activity has been found to be a useful guide to lead exposure for screening purposes. The pH of the test should be well-controlled for adequate clinical interpretation. False-normal tests are rare even with iron-deficiency anemia or macrocytosis. Recent transfusion and recent bleeding or hemolysis with reticulocytosis tend to invalidate the test. ALA-D activity above 600 International Units effectively excludes significant lead exposure and eliminates the need for further testing. ALA-D activity is maximally depressed at a red cell lead concentration of 200 mug per 100 ml. When activity is moderately depressed, interpretation is difficult and the urinary excretion of lead after the administration of a chelating agent is usually required to differentiate the degree and significance of lead exposure.", "contents": "Erythrocyte delta-aminolevulinic acid dehydratase activity as a measure of lead exposure. The measurement of erythrocyte delta-aminolevulinic acid dehydratase (ALA-D) activity has been found to be a useful guide to lead exposure for screening purposes. The pH of the test should be well-controlled for adequate clinical interpretation. False-normal tests are rare even with iron-deficiency anemia or macrocytosis. Recent transfusion and recent bleeding or hemolysis with reticulocytosis tend to invalidate the test. ALA-D activity above 600 International Units effectively excludes significant lead exposure and eliminates the need for further testing. ALA-D activity is maximally depressed at a red cell lead concentration of 200 mug per 100 ml. When activity is moderately depressed, interpretation is difficult and the urinary excretion of lead after the administration of a chelating agent is usually required to differentiate the degree and significance of lead exposure."}
{"id": "PMID:235594", "title": "Characterization of erythrocyte membrane-associated enzymes (glyceraldehyde-3-phosphate dehydrogenase and phosphoglyceric kinase).", "content": "The purpose of our study was to determine why several of the glycolytic enzymes of the erythrocyte have the propensity for adhering to erythrocyte membranes while others do not. Two of these membrane-associated enzymes, glyceraldehyde phosphate dehydrogenase (GAPD) and phosphoglyceric kinase (PGK), have been shown to have controlling functions on intra-erythrocytic glycolysis and sodium-potassium transport. In order to test the hypothesis that the membrane-associated fraction of these enzymes consisted of isozymes with increased capacity to become membrane associated, the enzymes from cytosol or membrane sources were partially purified and characterized. Determination of molecular weight by gel filtration chromatography, measurement of certain kinetic parameters, and the curves relating to pH optimal activity indicated that there were no measurable differences between membrane and cytosol PGK and membrane and cytosol GAPD. It was possible to raise inhibitory antibodies to GAPD in certain species of mice, and these antibodies did not distinguish between GAPD isolated from either membrane or cytosol sources. GAPD was firmly bound to membranes and the membrane-associated fraction counted for approximately 60 per cent of total erythrocytic enzyme. Membrane-associated PGK was only loosely adherent, and accounted for only 1 per cent of the total erythrocytic enzyme. The reasons for membrane association have yet to be determined, but these inward facing membrane-associated enzymes appear to function by carrying the organization of the membrane into the cell interior.", "contents": "Characterization of erythrocyte membrane-associated enzymes (glyceraldehyde-3-phosphate dehydrogenase and phosphoglyceric kinase). The purpose of our study was to determine why several of the glycolytic enzymes of the erythrocyte have the propensity for adhering to erythrocyte membranes while others do not. Two of these membrane-associated enzymes, glyceraldehyde phosphate dehydrogenase (GAPD) and phosphoglyceric kinase (PGK), have been shown to have controlling functions on intra-erythrocytic glycolysis and sodium-potassium transport. In order to test the hypothesis that the membrane-associated fraction of these enzymes consisted of isozymes with increased capacity to become membrane associated, the enzymes from cytosol or membrane sources were partially purified and characterized. Determination of molecular weight by gel filtration chromatography, measurement of certain kinetic parameters, and the curves relating to pH optimal activity indicated that there were no measurable differences between membrane and cytosol PGK and membrane and cytosol GAPD. It was possible to raise inhibitory antibodies to GAPD in certain species of mice, and these antibodies did not distinguish between GAPD isolated from either membrane or cytosol sources. GAPD was firmly bound to membranes and the membrane-associated fraction counted for approximately 60 per cent of total erythrocytic enzyme. Membrane-associated PGK was only loosely adherent, and accounted for only 1 per cent of the total erythrocytic enzyme. The reasons for membrane association have yet to be determined, but these inward facing membrane-associated enzymes appear to function by carrying the organization of the membrane into the cell interior."}
{"id": "PMID:235595", "title": "Factors affecting the evolution of factor XIa during blood coagulation.", "content": "Certain conditions affecting the evolution of factor XI-a activity during blood coagulation have been examined. Earlier data had indicated that calcium ion was not required for the conversion of factor XI to its activated form, but very little XI-a could be isolated from citrated or EDTA plasma, whether or not the plasma had been clotted by recalcification. Conversely, factor XI-a activity was identified in resin-decalcified plasma, again with or without recalcification. This confirmed that calcium is not required for the evolution of factor XI-a. This observation also permitted us to perform experiments which indicate that there is no obligatory participation of cellular elements in the evolution of factor XI-a during blood coagulation.", "contents": "Factors affecting the evolution of factor XIa during blood coagulation. Certain conditions affecting the evolution of factor XI-a activity during blood coagulation have been examined. Earlier data had indicated that calcium ion was not required for the conversion of factor XI to its activated form, but very little XI-a could be isolated from citrated or EDTA plasma, whether or not the plasma had been clotted by recalcification. Conversely, factor XI-a activity was identified in resin-decalcified plasma, again with or without recalcification. This confirmed that calcium is not required for the evolution of factor XI-a. This observation also permitted us to perform experiments which indicate that there is no obligatory participation of cellular elements in the evolution of factor XI-a during blood coagulation."}
{"id": "PMID:235596", "title": "A comparative chemical and serological study of the full and empty particles of foot-and mouth disease virus.", "content": "The chemical and serological properties of the full, naturally occurring empty and artificially produced empty particles of foot-and-mouth disease virus, serotype A(subtype 10, strain 16) have been studies. The full 146S particles comprised the virus RNA, three polypeptides (VP1 to VP3) mol. wt. about 30 X 10-3, one polypeptide (VP4) mol. wt. about 13-5 X 10-3, and a small amount of a polypeptide (VPo) mol. wt. about 43 X 10-3. The naturally occurring 75S empty particles contained no RNA and much less VP1 and VP4 than were found in the fall particles. However they contained a much greater proportion of VPo than the full particles. Dialysis of purified full particles against tris-EDTA, pH 7-6, produced artificial 75S empty particles which contained only a small amount of RNA and no VP4; otherwise the polypeptide composition was similar to that of the full particles. Immunological and serological tests showed that the full particles were antigenically similar to the naturally occurring empty particles but distinct from the artificial empty particles. The latter particles, however, had serological properties similar to those of the 12S protein subunit of the virus. Both the full and naturally occurring empty particles attached efficiently to susceptible cells, whereas the artificial empty particles attached only to a limited extent. The results are related to the function of the individual polypeptides of the virus particle and compared with published work on other picornaviruses.", "contents": "A comparative chemical and serological study of the full and empty particles of foot-and mouth disease virus. The chemical and serological properties of the full, naturally occurring empty and artificially produced empty particles of foot-and-mouth disease virus, serotype A(subtype 10, strain 16) have been studies. The full 146S particles comprised the virus RNA, three polypeptides (VP1 to VP3) mol. wt. about 30 X 10-3, one polypeptide (VP4) mol. wt. about 13-5 X 10-3, and a small amount of a polypeptide (VPo) mol. wt. about 43 X 10-3. The naturally occurring 75S empty particles contained no RNA and much less VP1 and VP4 than were found in the fall particles. However they contained a much greater proportion of VPo than the full particles. Dialysis of purified full particles against tris-EDTA, pH 7-6, produced artificial 75S empty particles which contained only a small amount of RNA and no VP4; otherwise the polypeptide composition was similar to that of the full particles. Immunological and serological tests showed that the full particles were antigenically similar to the naturally occurring empty particles but distinct from the artificial empty particles. The latter particles, however, had serological properties similar to those of the 12S protein subunit of the virus. Both the full and naturally occurring empty particles attached efficiently to susceptible cells, whereas the artificial empty particles attached only to a limited extent. The results are related to the function of the individual polypeptides of the virus particle and compared with published work on other picornaviruses."}
{"id": "PMID:235597", "title": "The phosphorylation of sendai virus proteins by a virus particle-associated protein kinase.", "content": "Highly purified Sendai virus contained a protein kinase activity which atatlysed the phosphorylation of endogenous polypeptides or exogenous protamine sulphate. The virus contained very low levels of phosphoprotein phosphatase activity. Polyacrylamide gel analysis of the reaction product indicated that the phosphorylation was specific for certain polypeptides and varied according to whether the virus was grown in eggs or in tissue culture. This variation was partially associated with the difference in the polypeptide pattern that occurred when the virus was grown in eggs or in tissue culture. Characterization of these phosphoproteins demonstrated that the phosphate was incorporated predominantly in a phosphoester linkage with theonine residues. Using a detergent and high salt solubilization procedure, the protein kinase activity was found associated within glycoprotein free virus particles but not with the nucleocapsid-associated polypeptides. In vivo phosphorylation occurred when Sendai virus was grown in eggs or in tissue culture with [32P] and the phosphorylated polypeptides were similar to those of the protein kinase reaction product. Phosphorylation could also be detected in the infected cell and could occur once the virus particle polypeptides were being synthesized. The non-structural polypeptides were not phosphorylated.", "contents": "The phosphorylation of sendai virus proteins by a virus particle-associated protein kinase. Highly purified Sendai virus contained a protein kinase activity which atatlysed the phosphorylation of endogenous polypeptides or exogenous protamine sulphate. The virus contained very low levels of phosphoprotein phosphatase activity. Polyacrylamide gel analysis of the reaction product indicated that the phosphorylation was specific for certain polypeptides and varied according to whether the virus was grown in eggs or in tissue culture. This variation was partially associated with the difference in the polypeptide pattern that occurred when the virus was grown in eggs or in tissue culture. Characterization of these phosphoproteins demonstrated that the phosphate was incorporated predominantly in a phosphoester linkage with theonine residues. Using a detergent and high salt solubilization procedure, the protein kinase activity was found associated within glycoprotein free virus particles but not with the nucleocapsid-associated polypeptides. In vivo phosphorylation occurred when Sendai virus was grown in eggs or in tissue culture with [32P] and the phosphorylated polypeptides were similar to those of the protein kinase reaction product. Phosphorylation could also be detected in the infected cell and could occur once the virus particle polypeptides were being synthesized. The non-structural polypeptides were not phosphorylated."}
{"id": "PMID:235604", "title": "Attitudes toward death: a survey of nursing students.", "content": "The literature devoted to the topics of death and care of the dying is expanding rapidly. As nurses are inevitably involved in terminal illness, death and grief, their attitudes toward death and factors which affect these attitudes, are worthy of study. This report describes the results of a continuing two-year survey of one class of students in a baccalaureate nursing program. A questionnaire was used at the beginning and end of one academic year. Data were obtained regarding background experiences with death, involvement in the care of dying patients, and common ideas, concerns and feelings about death. Data from the second testing also included perceived changes in \"positive\" and \"negative\" attitudes toward death, and the relative effect on attitudes of various factors during the year. Suggestions are offered for curriculum development and research in the challenging area of death education in nursing.", "contents": "Attitudes toward death: a survey of nursing students. The literature devoted to the topics of death and care of the dying is expanding rapidly. As nurses are inevitably involved in terminal illness, death and grief, their attitudes toward death and factors which affect these attitudes, are worthy of study. This report describes the results of a continuing two-year survey of one class of students in a baccalaureate nursing program. A questionnaire was used at the beginning and end of one academic year. Data were obtained regarding background experiences with death, involvement in the care of dying patients, and common ideas, concerns and feelings about death. Data from the second testing also included perceived changes in \"positive\" and \"negative\" attitudes toward death, and the relative effect on attitudes of various factors during the year. Suggestions are offered for curriculum development and research in the challenging area of death education in nursing."}
{"id": "PMID:235607", "title": "Translocation of the umbilical artery to the lower abdomen: an adjunct to the postoperative monitoring of arterial blood gases in major abdominal wall defects.", "content": "A technique is presented for preserving the umbilical arteries for postoperative monitoring of arterial blood gases after repair of giant omphaloceles and gastroschisis. Translocation of the arteries to the lower abdominal wall removes them from the operative field and allows cannulation and long-term blood sampling. Complications have been minimal and the improved application of modern pulmonary support mechanisms has materially contributed to better patient management. The technique is a simple one and may prove applicable to other major newborn medical and surgical diseases involving respiratory insufficiency.", "contents": "Translocation of the umbilical artery to the lower abdomen: an adjunct to the postoperative monitoring of arterial blood gases in major abdominal wall defects. A technique is presented for preserving the umbilical arteries for postoperative monitoring of arterial blood gases after repair of giant omphaloceles and gastroschisis. Translocation of the arteries to the lower abdominal wall removes them from the operative field and allows cannulation and long-term blood sampling. Complications have been minimal and the improved application of modern pulmonary support mechanisms has materially contributed to better patient management. The technique is a simple one and may prove applicable to other major newborn medical and surgical diseases involving respiratory insufficiency."}
{"id": "PMID:235608", "title": "Improvement of solubility and dissolution rate of poorly water-soluble salicylic acid by a spray-drying technique.", "content": "Spray drying techniques have been applied to improve the solubility and dissolution rate of poorly water-soluble salicylic acid. Spray drying of the acid dispersed in acacia solutions resulted in as much as a 50% improvement in the solubility of the product. Solubility improvement was closely related not only to the concentration of acacia but also the amount of amorphous material in the spray-dried products. The heat of solution was inversely related to these parameters. The dissolution rate of spray-dried product was almost instantaneous being about 60 times faster than that of the original powder. A great improvement in the wettability of the spray-dried material seemed to be mainly responsible for the increase of dissolution rate.", "contents": "Improvement of solubility and dissolution rate of poorly water-soluble salicylic acid by a spray-drying technique. Spray drying techniques have been applied to improve the solubility and dissolution rate of poorly water-soluble salicylic acid. Spray drying of the acid dispersed in acacia solutions resulted in as much as a 50% improvement in the solubility of the product. Solubility improvement was closely related not only to the concentration of acacia but also the amount of amorphous material in the spray-dried products. The heat of solution was inversely related to these parameters. The dissolution rate of spray-dried product was almost instantaneous being about 60 times faster than that of the original powder. A great improvement in the wettability of the spray-dried material seemed to be mainly responsible for the increase of dissolution rate."}
{"id": "PMID:235609", "title": "A crystallographic and theoretical study of the conformation of DOET and its significance for the hallucinogenic amphetamines.", "content": "The crystal and molecular structure of 2, 5-dimethoxy-4-ethyl-alpha-methyl-phenylethylamine (DOET) has been determined by X-ray crystallography and the conformation of the side chain has been examined theoretically by the use of a potential energy calculation. There is no indication in the solid state of any intra or inter-molecular hydrogen bonding. The isopropylamine side chain is staggered to the plane of the benzene ring. The alpha-methyl group is fully extended (antiplanar) whereas the amino group is orientated back towards the ring (synclinal). The potential energy calculations show the existence of 6 minima, one of which corresponds to the crystal position. The calculations also show that the energy differences between the various minima of the side chain are very small. The relationship of these data to the conformations of the hallucinogens, mescaline and 2, 4, 5,-trimethoxyamphetamine is discussed.", "contents": "A crystallographic and theoretical study of the conformation of DOET and its significance for the hallucinogenic amphetamines. The crystal and molecular structure of 2, 5-dimethoxy-4-ethyl-alpha-methyl-phenylethylamine (DOET) has been determined by X-ray crystallography and the conformation of the side chain has been examined theoretically by the use of a potential energy calculation. There is no indication in the solid state of any intra or inter-molecular hydrogen bonding. The isopropylamine side chain is staggered to the plane of the benzene ring. The alpha-methyl group is fully extended (antiplanar) whereas the amino group is orientated back towards the ring (synclinal). The potential energy calculations show the existence of 6 minima, one of which corresponds to the crystal position. The calculations also show that the energy differences between the various minima of the side chain are very small. The relationship of these data to the conformations of the hallucinogens, mescaline and 2, 4, 5,-trimethoxyamphetamine is discussed."}
{"id": "PMID:235610", "title": "Some pharmacological actions of 2,5-dimethoxy-4-ethylamphetamine (DOET) in rats and mice.", "content": "DOET, like DOM, exhibited pressor action in rats. This increase of blood pressure was blocked by pretreatment with cinanserin. DOET at high doses decreased the spontaneous locomotor activity of mice at the first hour but increased the activity at the second hour; a low dose was less effective. DOET also increased the rectal temperature of rats and this hyperthermic action was suppressed by pretreating the animals with cinanserin or methysergide. These actions of DOET were compared with those of DOM.", "contents": "Some pharmacological actions of 2,5-dimethoxy-4-ethylamphetamine (DOET) in rats and mice. DOET, like DOM, exhibited pressor action in rats. This increase of blood pressure was blocked by pretreatment with cinanserin. DOET at high doses decreased the spontaneous locomotor activity of mice at the first hour but increased the activity at the second hour; a low dose was less effective. DOET also increased the rectal temperature of rats and this hyperthermic action was suppressed by pretreating the animals with cinanserin or methysergide. These actions of DOET were compared with those of DOM."}
{"id": "PMID:235611", "title": "Comparison of the beta-adrenoceptors in the myocardium and coronary vasculature of the kitten heart.", "content": "The relative potencies of (minus) noradrenaline, (minus)-adrenaline, (plus or minus)-isoprenaline and (plus or minus)-salbutamol have been assessed for their positive inotropic and chronotropic actions on kitten isolated atria. These relative potencies have been compared with those obtained for the relative coronary dilator potencies in two preparations. These were intact hearts perfused by Langendorff's method and isolated perfused coronary arteries from the kitten. The relative molar potencies for inotropic effects were noradrenaline 1: adrenaline1: iso-prenaline 7: salbutamol 0.6. The observed ratios for chronotropic effects were not significantly different from those for inotropic effects. The relative potencies of noradrenaline, adrenaline and isoprenaline as myocardial stimulants were similar to their relative potencies as coronary dilators in the intact heart. Similar relative potencies for noradrenaline and isoprenaline were also found in the isolated coronary artery but adrenaline was only one third as active as noradrenaline on this preparation. In both the intact heart and in the isolated coronary artery salbutamol was about one tenth as active as noradrenaline. It was therefore less active relative to noradrenaline as a coronary dilator than as a myocardial stimulant. In spite of these differences in relative potency ratios for myocardial and coronary dilator effects, similar dissociation constants (Kb values) for practolol against isoprenaline were found in driven atria and in isolated coronary arteries. Myocardial and coronary vascular beta-adrenoceptors thus can both be placed in the general classification of beta1-adrenoceptors.", "contents": "Comparison of the beta-adrenoceptors in the myocardium and coronary vasculature of the kitten heart. The relative potencies of (minus) noradrenaline, (minus)-adrenaline, (plus or minus)-isoprenaline and (plus or minus)-salbutamol have been assessed for their positive inotropic and chronotropic actions on kitten isolated atria. These relative potencies have been compared with those obtained for the relative coronary dilator potencies in two preparations. These were intact hearts perfused by Langendorff's method and isolated perfused coronary arteries from the kitten. The relative molar potencies for inotropic effects were noradrenaline 1: adrenaline1: iso-prenaline 7: salbutamol 0.6. The observed ratios for chronotropic effects were not significantly different from those for inotropic effects. The relative potencies of noradrenaline, adrenaline and isoprenaline as myocardial stimulants were similar to their relative potencies as coronary dilators in the intact heart. Similar relative potencies for noradrenaline and isoprenaline were also found in the isolated coronary artery but adrenaline was only one third as active as noradrenaline on this preparation. In both the intact heart and in the isolated coronary artery salbutamol was about one tenth as active as noradrenaline. It was therefore less active relative to noradrenaline as a coronary dilator than as a myocardial stimulant. In spite of these differences in relative potency ratios for myocardial and coronary dilator effects, similar dissociation constants (Kb values) for practolol against isoprenaline were found in driven atria and in isolated coronary arteries. Myocardial and coronary vascular beta-adrenoceptors thus can both be placed in the general classification of beta1-adrenoceptors."}
{"id": "PMID:235612", "title": "The effect of 5-hydroxytryptophan on food intake and on the anorexic action of amphetamine and fenfluramine.", "content": "5-Hydroxytryptophan (5-HTP), amphetamine and fenfluramine suppressed food intake in normal rats and in aminals with lesions of the lateral hypothalamus. The anorexic effect of amphetamine was reduced in lesioned animals compared with controls while the effect of 5-HTP like that of fenfluramine was increased. When administered in conjunction with anorexic drugs, 5-HTP markedly potentiated the anorexic effect of amphetamine in both control and lesioned animals. However, 5-HTP potentiated fenfluramine anorexia only in lesioned rats. These findings provide further evidence for the role of 5-hydroxytryptamine (5-HT,in the anorexic effect of fenfluramine, and suggest that a 5-HT mechanism, inhibitory for feeding, produces particulary severe suppression of food intake in rats with lateral hypothalamic lesions.", "contents": "The effect of 5-hydroxytryptophan on food intake and on the anorexic action of amphetamine and fenfluramine. 5-Hydroxytryptophan (5-HTP), amphetamine and fenfluramine suppressed food intake in normal rats and in aminals with lesions of the lateral hypothalamus. The anorexic effect of amphetamine was reduced in lesioned animals compared with controls while the effect of 5-HTP like that of fenfluramine was increased. When administered in conjunction with anorexic drugs, 5-HTP markedly potentiated the anorexic effect of amphetamine in both control and lesioned animals. However, 5-HTP potentiated fenfluramine anorexia only in lesioned rats. These findings provide further evidence for the role of 5-hydroxytryptamine (5-HT,in the anorexic effect of fenfluramine, and suggest that a 5-HT mechanism, inhibitory for feeding, produces particulary severe suppression of food intake in rats with lateral hypothalamic lesions."}
{"id": "PMID:235613", "title": "The role of p-hydroxylation of amphetamine in its peripheral mode of action.", "content": "Desipramine completely abolished the blood pressure response to (+) amphetamine in the rat, whereas the tricyclic antidepressant iprindole did not reduce this response. Since both tricyclic drugs inhibit the aromatic hydroxylation of amphetamine, these studies do not support the hypothesis that hydroxylated metabolites of amphetamine, p-hydroxyamphetamine and p-hydroxynorephedrine are essential for the peripheral sympathomimetic effects of amphetamine.", "contents": "The role of p-hydroxylation of amphetamine in its peripheral mode of action. Desipramine completely abolished the blood pressure response to (+) amphetamine in the rat, whereas the tricyclic antidepressant iprindole did not reduce this response. Since both tricyclic drugs inhibit the aromatic hydroxylation of amphetamine, these studies do not support the hypothesis that hydroxylated metabolites of amphetamine, p-hydroxyamphetamine and p-hydroxynorephedrine are essential for the peripheral sympathomimetic effects of amphetamine."}
{"id": "PMID:235614", "title": "Construction and implantation of a cannula system for repeated injections into localized regions of the rat brain.", "content": "The construction and method of implantation of a brain cannula for chronic use in rats is described. All the components of the cannula system are easily made from stainless steel tubing and no machined parts are required. The use of a metal key eliminates the need for tapped holes during implantation. Although little time is required to prepare each animal the system remains firmly fixed to the skull and allows injections to be made accurately into selected brain areas.", "contents": "Construction and implantation of a cannula system for repeated injections into localized regions of the rat brain. The construction and method of implantation of a brain cannula for chronic use in rats is described. All the components of the cannula system are easily made from stainless steel tubing and no machined parts are required. The use of a metal key eliminates the need for tapped holes during implantation. Although little time is required to prepare each animal the system remains firmly fixed to the skull and allows injections to be made accurately into selected brain areas."}
{"id": "PMID:235622", "title": "An automated sedimentation balance.", "content": "A method of size grading powders using an automated sedimentation balance is described. The results are recorded as percentages of the total powder present in 1 or 5 mum (intervals) of particle size, after they have been multiplied by a simple correction factor. Analyses of calcium carbonate powder using this balance and the Gallenkamp balance have been compared.", "contents": "An automated sedimentation balance. A method of size grading powders using an automated sedimentation balance is described. The results are recorded as percentages of the total powder present in 1 or 5 mum (intervals) of particle size, after they have been multiplied by a simple correction factor. Analyses of calcium carbonate powder using this balance and the Gallenkamp balance have been compared."}
{"id": "PMID:235629", "title": "Nerve stimulation-meditated overflow of norepinephrine and dopamine-beta-hydroxylase. III. Effects of norepinephrine depletion on the alpha presynaptic regulation of release.", "content": "A frequency-dependent increase in the overflow of norepinephrine (NE), 3-H-NE, total 3-H and dopamine-beta-hydroxylase (DBH) activity per nerve impulse was obtained after electrical stimulation of the isolated, perfused cat spleen. Over the range of frequencies studied, a proportional increase in the overflow of transmitter and DBH activity was observed, suggesting that an increase in the exocytotic release of NE is the primary mechanism by which the overflow of transmitter is enhanced with increasing frequencies of stimulation. The effects of 3 muM phenoxybenzamine (PBA) on the nerve stimulation-mediated overflow of NE, total 3-h, 3-h-ne and DBH activity were studied at two frequencies of stimulation, 1 and 5 Hz, in spleens from control and alpha-methyl-p-tyrosine-treated cats. Similarly, release of DBH activity was studied in spleens of reserpine-treated cats. In spleens from control cats, PBA produced a marked increase in the overflow of transmitter and DBH activity. This enhancement was more pronounced at 5 Hz than at 1 Hz. It was estimated that only 10 and 25% of the overflow of NE obtained in the presence of PBA at 1 and 5 Hz, respectively, could be accounted for by increased exocytosis. Depletion of tissue NE (80%) by pretreatment with alpha-methyl-p-tyrosine considerably reduced the effectiveness of PBA in enhancing the nerve stimulation-mediated overflow of NE, 3-H-NE, total 3-H and, particularly, of DBH activity. After reserpine treatment, the tissue NE content was reduced by more than 99%, yet the nerve stimulation-mediated release of DBH activity was similar to control spleens. PBA failed to enhance the nerve stimulation-mediated overflow of DBH activity after reserpine treatment. Thus it appears that the enhancement in the exocytotic release of transmitter by nerve stimulation observed in the presence of PBA is related to the concentration of NE in the synaptic space. Therefore, the present study is in favor of the notion that presynaptic alphareceptors may form part of a negative feedback control mechanism by which the transmitter may inhibit its own release.", "contents": "Nerve stimulation-meditated overflow of norepinephrine and dopamine-beta-hydroxylase. III. Effects of norepinephrine depletion on the alpha presynaptic regulation of release. A frequency-dependent increase in the overflow of norepinephrine (NE), 3-H-NE, total 3-H and dopamine-beta-hydroxylase (DBH) activity per nerve impulse was obtained after electrical stimulation of the isolated, perfused cat spleen. Over the range of frequencies studied, a proportional increase in the overflow of transmitter and DBH activity was observed, suggesting that an increase in the exocytotic release of NE is the primary mechanism by which the overflow of transmitter is enhanced with increasing frequencies of stimulation. The effects of 3 muM phenoxybenzamine (PBA) on the nerve stimulation-mediated overflow of NE, total 3-h, 3-h-ne and DBH activity were studied at two frequencies of stimulation, 1 and 5 Hz, in spleens from control and alpha-methyl-p-tyrosine-treated cats. Similarly, release of DBH activity was studied in spleens of reserpine-treated cats. In spleens from control cats, PBA produced a marked increase in the overflow of transmitter and DBH activity. This enhancement was more pronounced at 5 Hz than at 1 Hz. It was estimated that only 10 and 25% of the overflow of NE obtained in the presence of PBA at 1 and 5 Hz, respectively, could be accounted for by increased exocytosis. Depletion of tissue NE (80%) by pretreatment with alpha-methyl-p-tyrosine considerably reduced the effectiveness of PBA in enhancing the nerve stimulation-mediated overflow of NE, 3-H-NE, total 3-H and, particularly, of DBH activity. After reserpine treatment, the tissue NE content was reduced by more than 99%, yet the nerve stimulation-mediated release of DBH activity was similar to control spleens. PBA failed to enhance the nerve stimulation-mediated overflow of DBH activity after reserpine treatment. Thus it appears that the enhancement in the exocytotic release of transmitter by nerve stimulation observed in the presence of PBA is related to the concentration of NE in the synaptic space. Therefore, the present study is in favor of the notion that presynaptic alphareceptors may form part of a negative feedback control mechanism by which the transmitter may inhibit its own release."}
{"id": "PMID:235630", "title": "Cardiovascular effects of acute and chronic inhalations of fluorocarbon 12 in rabbits.", "content": "The effects of inhaling fluorocarbon 12, a common propellant in household aerosols, were studied in closed-chested rabbits. Inhalation of 10 or 20% fluorocarbon 12 produced a decline in cardiac output and a dose-related depression of peak left ventricular (LV) dP/dt without associated arrthythmias, hypoxemia or significant changes in LV end-diastolicpressue or heart rate. There was a small decline in LV systolic pressure without a significant drop in mean arterial pressure. Breathing fluorocarbon 12 for 30 minutes caused a decline in peak LV dP/dt, cardiac output, LV systolic pressure and mean arterial pressure which was present throughout the exposure period. The effects observed during acute fluorocarbon 12 exposure were not altered by previous chronic, intermittent exposure to 10% fluorocarbon 12.", "contents": "Cardiovascular effects of acute and chronic inhalations of fluorocarbon 12 in rabbits. The effects of inhaling fluorocarbon 12, a common propellant in household aerosols, were studied in closed-chested rabbits. Inhalation of 10 or 20% fluorocarbon 12 produced a decline in cardiac output and a dose-related depression of peak left ventricular (LV) dP/dt without associated arrthythmias, hypoxemia or significant changes in LV end-diastolicpressue or heart rate. There was a small decline in LV systolic pressure without a significant drop in mean arterial pressure. Breathing fluorocarbon 12 for 30 minutes caused a decline in peak LV dP/dt, cardiac output, LV systolic pressure and mean arterial pressure which was present throughout the exposure period. The effects observed during acute fluorocarbon 12 exposure were not altered by previous chronic, intermittent exposure to 10% fluorocarbon 12."}
{"id": "PMID:235631", "title": "Effects of exercise metabolites on adrenergic vasoconstriction in the gracilis muscle of the dog.", "content": "Comparable and submaximal responses to sympathetic stimulation and to intra-arterial injections and infusions of norepinephrine were elicited in the isolated dog gracilis muscle, perfused with blood at constantflow. The changes in potassium concentration, osmolality, Po2 and inorganic phosphate concentration were determined during exercise. Blood was perfused to the muscle with the concentrations of each of these parameters varied to include that seen in exercise. Hypoxia (average Po2 5.4 mm Hg) produced a marked vasodilatation, and responses to norepinephrine and sympathetic stimulation were both increased to the same extent, due to the lowered vascular tone. Increases in osmolality (up to 50 mOsmol/kg) caused little antagonism of adrenergic responses, but higher increases caused a significant and equal inhibition of responses to norepinephrine and sympathetic stimulation. Increases in phosphate concentration (plus 41.6 mM) had little effect either on muscle resistance or on adrenergic responses. Increases in potassium concentration (plus10 mM) completely abolished responses to sympathetic stimulation, whereas those to norepinephrine were unaffected. This prejunctional effect may result from inhibition of sympathetic neurotransmission due to depolarization of adrenergic nerve terminals.", "contents": "Effects of exercise metabolites on adrenergic vasoconstriction in the gracilis muscle of the dog. Comparable and submaximal responses to sympathetic stimulation and to intra-arterial injections and infusions of norepinephrine were elicited in the isolated dog gracilis muscle, perfused with blood at constantflow. The changes in potassium concentration, osmolality, Po2 and inorganic phosphate concentration were determined during exercise. Blood was perfused to the muscle with the concentrations of each of these parameters varied to include that seen in exercise. Hypoxia (average Po2 5.4 mm Hg) produced a marked vasodilatation, and responses to norepinephrine and sympathetic stimulation were both increased to the same extent, due to the lowered vascular tone. Increases in osmolality (up to 50 mOsmol/kg) caused little antagonism of adrenergic responses, but higher increases caused a significant and equal inhibition of responses to norepinephrine and sympathetic stimulation. Increases in phosphate concentration (plus 41.6 mM) had little effect either on muscle resistance or on adrenergic responses. Increases in potassium concentration (plus10 mM) completely abolished responses to sympathetic stimulation, whereas those to norepinephrine were unaffected. This prejunctional effect may result from inhibition of sympathetic neurotransmission due to depolarization of adrenergic nerve terminals."}
{"id": "PMID:235632", "title": "Effects of prostaglandins B2 and B1 on the pulmonary circulation in the intact dog.", "content": "The effects of prostaglandins (PG) B2 and B1 on the pulmonary circulation were studied in the intact spontaneously breathing dog under conditions of controlled blood flow using right heart and transseptal catheterization techniques to isolate and perfuse the left lower lung lobe. Infusion of PGB2 and PGB1 into the left lower lung lobe increased lobar arterial and lobar venous pressure but had no significant effect on left atrial pressure. PGB2 and PGB1 increased pressure gradients between the lobar artery and lobar small vein and between the lobar small vein and the left atrium. PGB2 and PGB1 increased isometric tension in isolated helical segments of lobar vein (3-5 mm diameter) but had little or no effect on lobar arterial segments of the same size. These results indicate that in the intact dog prostaglandins of the B series increase pulmonary vascular resistance by constricting lobar veins and to a lesser extent vessels upstream to lobar small veins, presumably small lobar arteries. PGB2 and PGB1 both produced large increases in pulmonary vascular resistance in the dog with PGB2 being about 10 times as potent as PGB1. It is concluded that PGB2 is one of the most potent pressor substances in the canine pulmonary vascular bed.", "contents": "Effects of prostaglandins B2 and B1 on the pulmonary circulation in the intact dog. The effects of prostaglandins (PG) B2 and B1 on the pulmonary circulation were studied in the intact spontaneously breathing dog under conditions of controlled blood flow using right heart and transseptal catheterization techniques to isolate and perfuse the left lower lung lobe. Infusion of PGB2 and PGB1 into the left lower lung lobe increased lobar arterial and lobar venous pressure but had no significant effect on left atrial pressure. PGB2 and PGB1 increased pressure gradients between the lobar artery and lobar small vein and between the lobar small vein and the left atrium. PGB2 and PGB1 increased isometric tension in isolated helical segments of lobar vein (3-5 mm diameter) but had little or no effect on lobar arterial segments of the same size. These results indicate that in the intact dog prostaglandins of the B series increase pulmonary vascular resistance by constricting lobar veins and to a lesser extent vessels upstream to lobar small veins, presumably small lobar arteries. PGB2 and PGB1 both produced large increases in pulmonary vascular resistance in the dog with PGB2 being about 10 times as potent as PGB1. It is concluded that PGB2 is one of the most potent pressor substances in the canine pulmonary vascular bed."}
{"id": "PMID:235633", "title": "Renal mechanisms for the excretion of nicotinic acid.", "content": "Nicotinic acid, an essential endogenous organic acid, was studied in free-flow clearance experiments in the dog at plasma concentrations ranging from 1.2 to 600 mug/ml. At all concentrations, net reabsorption was observed. At concentrations of 1.2 mug/ml, the clearance of nicotinic acid as compared to the clearance of insulin was approximately 0.50. As nicotinic acid plasma concentrations were increased to 90 mug/ml, the clearance ratio declined to 0.22. The clearance ratio then steadily increased to 0.75 as plasma concentrations reached 600 mug/ml. Plasma levels of nicotinic acid in excess of 600 mug/ml resulted in renal toxicity as indicated by a marked decrease in the glomerular filtration rate. The decline in the clearance ratio in the presence of 90 mug/ml of nicotinic acid suggested saturation of a secretory system and hence cyanine 863 and probenecid were used to observe their effects on the clearance ratio. The base transport inhibitor was without effect; probenecid decreased the clearance. Alkalinization of the urine had no noticeable effect on nicotinic acid clearance. Protein binding did not occur. The data indicate two important points. First, nicotinic acid is secreted to a limited degree by the organic anion secretory system and is simultaneously reabsorbed. Second, a homeostatic mechanism for conservation of nicotinic acid at low plasma levels does not seem to exist.", "contents": "Renal mechanisms for the excretion of nicotinic acid. Nicotinic acid, an essential endogenous organic acid, was studied in free-flow clearance experiments in the dog at plasma concentrations ranging from 1.2 to 600 mug/ml. At all concentrations, net reabsorption was observed. At concentrations of 1.2 mug/ml, the clearance of nicotinic acid as compared to the clearance of insulin was approximately 0.50. As nicotinic acid plasma concentrations were increased to 90 mug/ml, the clearance ratio declined to 0.22. The clearance ratio then steadily increased to 0.75 as plasma concentrations reached 600 mug/ml. Plasma levels of nicotinic acid in excess of 600 mug/ml resulted in renal toxicity as indicated by a marked decrease in the glomerular filtration rate. The decline in the clearance ratio in the presence of 90 mug/ml of nicotinic acid suggested saturation of a secretory system and hence cyanine 863 and probenecid were used to observe their effects on the clearance ratio. The base transport inhibitor was without effect; probenecid decreased the clearance. Alkalinization of the urine had no noticeable effect on nicotinic acid clearance. Protein binding did not occur. The data indicate two important points. First, nicotinic acid is secreted to a limited degree by the organic anion secretory system and is simultaneously reabsorbed. Second, a homeostatic mechanism for conservation of nicotinic acid at low plasma levels does not seem to exist."}
{"id": "PMID:235634", "title": "Urinary excretion of morphine and its metabolites in morphine-dependent subjects.", "content": "Morphine, morphine glucuronide, morphine ethereal sulfate, normorphine and total normorphine in three consecutive 24-hour urines of four morphine-dependent subjects receiving morphine sulfate 60 mg s.c. q.i.d. have been determined with thin-layer chromatography and gas-liquid chromatography. With thin-layer chromatography the mean daily excretion of free morphine was 10% of the administered dose; morphine glucuronide, 65%; total (free and acid hydrolyzable conjugate) morphine 85%; and total normorphine, 3.5%. With gas-liquid chromatography, the percentage excretion for free morphine was 10%; total morphine, 74%; free normorphine, 1%; and total normorphine, 4%. The excretion of total drug was linearly related to the volume of the daily urine output.", "contents": "Urinary excretion of morphine and its metabolites in morphine-dependent subjects. Morphine, morphine glucuronide, morphine ethereal sulfate, normorphine and total normorphine in three consecutive 24-hour urines of four morphine-dependent subjects receiving morphine sulfate 60 mg s.c. q.i.d. have been determined with thin-layer chromatography and gas-liquid chromatography. With thin-layer chromatography the mean daily excretion of free morphine was 10% of the administered dose; morphine glucuronide, 65%; total (free and acid hydrolyzable conjugate) morphine 85%; and total normorphine, 3.5%. With gas-liquid chromatography, the percentage excretion for free morphine was 10%; total morphine, 74%; free normorphine, 1%; and total normorphine, 4%. The excretion of total drug was linearly related to the volume of the daily urine output."}
{"id": "PMID:235635", "title": "Regulation of cyclic adenosine 3',5'-monophosphate levels in guinea-pig cerebral cortex by interaction of alpha adrenergic and adenosine receptor activity.", "content": "Direct assay of adenosine 3',5'-monophosphate (cyclic AMP) in guinea-pig cerebral cortex in vitro has shown that an alpha adrenergic receptor that was previously found to increase tissue content of cyclic AMP requires the co-presence of adenosine. This alpha adrenergic receptor complex was characterized with blocking agents and contrasted with other activities by examining the effect of other biogenic amines on cyclic AMP content in the presence of adenosine. Phentolamine (but not propranolol) reduced the potentiated response to norepinephrine (NE) (or epinephrine) plus adenosine to the level seen with adenosine alone. Theophylline, an adenosine antagonist, blocked the entire effect of NE plus adenosine. The failure of a high Mg++/Ca++ ratio to block the effect of NE plus adenosine argues against indirect mediation of the alpha receptor effect via the release of K+ or via an unknown neurohumoral agent. The complex variety of potentiative interactions between biogenic amines and adenosine is unique to brain. These interactions may be explained by the proposed existence of both independent and dependent receptors. The dependent receptors respond only to the co-presence of two or more neurohumoral agents. An alternative explanation would involve a compartmentally selective impairment of cyclic AMP degradation.", "contents": "Regulation of cyclic adenosine 3',5'-monophosphate levels in guinea-pig cerebral cortex by interaction of alpha adrenergic and adenosine receptor activity. Direct assay of adenosine 3',5'-monophosphate (cyclic AMP) in guinea-pig cerebral cortex in vitro has shown that an alpha adrenergic receptor that was previously found to increase tissue content of cyclic AMP requires the co-presence of adenosine. This alpha adrenergic receptor complex was characterized with blocking agents and contrasted with other activities by examining the effect of other biogenic amines on cyclic AMP content in the presence of adenosine. Phentolamine (but not propranolol) reduced the potentiated response to norepinephrine (NE) (or epinephrine) plus adenosine to the level seen with adenosine alone. Theophylline, an adenosine antagonist, blocked the entire effect of NE plus adenosine. The failure of a high Mg++/Ca++ ratio to block the effect of NE plus adenosine argues against indirect mediation of the alpha receptor effect via the release of K+ or via an unknown neurohumoral agent. The complex variety of potentiative interactions between biogenic amines and adenosine is unique to brain. These interactions may be explained by the proposed existence of both independent and dependent receptors. The dependent receptors respond only to the co-presence of two or more neurohumoral agents. An alternative explanation would involve a compartmentally selective impairment of cyclic AMP degradation."}
{"id": "PMID:235636", "title": "The effect of liver disease in man on the disposition of phenobarbital.", "content": "The disposition of phenobarbital (PB) was studied in normal individuals and in patients with cirrhosis or acute viral hepatitis to determine 1) if there is significant impairment of PB metabolism in hepatic disease and 2) to what extent such abnormal disposition of the drug affects its disappearance from blood. The diagnosis of liver disease was based on characteristic clinical findings, biochemical liver \"function\" tests and liver biopsy when necessary. All individuals had normal renal function and were free of other drug and alcohol intake for at least 3 weeks. With radiotracer methodology, PB and its principal metabolites, p-hydroxyphenobarbital (PBOH) and conjugated PBOH (PBOC), were monitored in blood and urine for 5 days after a single dose of 14-C-PBadministered intraduodenally. PB blood half-life (T1/2) in the control group was 86 plus or minus 3 hours (S.E.). In cirrhotics the T1/2 was prolonged to 130 plus or minus 15 hours (P less than .001) and this was accompanied by a 50% reduction in urinary PBOC excretion (P less than .05). Urinary excretion of PB and PBOH was unaltered by cirrhosis. In patients with acute viral hepatitis, PB T1/2 was not significantly prolonged and urinary excretion of PB and its metabolites was in the normal range (P greater than .05). No PBOH and only traces of PBOC were detected in the blood of either control individuals or patients with liver disease. Urinary excretion of unchanged PB was an important elimination pathway of the drug in all groups. As a result of this, PB T1/2 in cirrhosis was only moderately prolonged.", "contents": "The effect of liver disease in man on the disposition of phenobarbital. The disposition of phenobarbital (PB) was studied in normal individuals and in patients with cirrhosis or acute viral hepatitis to determine 1) if there is significant impairment of PB metabolism in hepatic disease and 2) to what extent such abnormal disposition of the drug affects its disappearance from blood. The diagnosis of liver disease was based on characteristic clinical findings, biochemical liver \"function\" tests and liver biopsy when necessary. All individuals had normal renal function and were free of other drug and alcohol intake for at least 3 weeks. With radiotracer methodology, PB and its principal metabolites, p-hydroxyphenobarbital (PBOH) and conjugated PBOH (PBOC), were monitored in blood and urine for 5 days after a single dose of 14-C-PBadministered intraduodenally. PB blood half-life (T1/2) in the control group was 86 plus or minus 3 hours (S.E.). In cirrhotics the T1/2 was prolonged to 130 plus or minus 15 hours (P less than .001) and this was accompanied by a 50% reduction in urinary PBOC excretion (P less than .05). Urinary excretion of PB and PBOH was unaltered by cirrhosis. In patients with acute viral hepatitis, PB T1/2 was not significantly prolonged and urinary excretion of PB and its metabolites was in the normal range (P greater than .05). No PBOH and only traces of PBOC were detected in the blood of either control individuals or patients with liver disease. Urinary excretion of unchanged PB was an important elimination pathway of the drug in all groups. As a result of this, PB T1/2 in cirrhosis was only moderately prolonged."}
{"id": "PMID:235637", "title": "Effect of prolactin on androgen metabolism by the guinea-pig sex accessory organs.", "content": "The in vitro actions of prolactin on the metabolism of testosterone by the guinea-pig liver and sex accessory organs have been investigated under a variety of conditions including various concentrations of ovine or bovine prolactin, addition of reduced nicotinamide adenine dinucleotide phosphatate (NADPH) or nicotinamide adenine dinucleotide (NAD) to incubation media and various lengths of incubations. Treatment of the epithelium and muscle of the guinea-pig seminal vesicle with NAD elicited a shift from normal reductive metabolism of testosterone toward oxidative metabolism. This shift toward oxidative metabolism of testosterone was particularly marked in the muscle of the guinea-pig seminal vesicle. Ovine prolactin was highly effective in inhibiting the reductive metabolism of testosterone by the sex accessory organs. This effect appeared primarily as a decrease in dihydrotestosterone formation and was noted in both the presence and absence of NADPH or NAD. Oxidized metabolites, androstenedione and androstandione, were apparently insensitive to prolactin treatment in vitro. Variations induced by prolactin in the concentrations of intracellular androgens may be important in either the normal or abnormal growth and function of male sex accessory organs.", "contents": "Effect of prolactin on androgen metabolism by the guinea-pig sex accessory organs. The in vitro actions of prolactin on the metabolism of testosterone by the guinea-pig liver and sex accessory organs have been investigated under a variety of conditions including various concentrations of ovine or bovine prolactin, addition of reduced nicotinamide adenine dinucleotide phosphatate (NADPH) or nicotinamide adenine dinucleotide (NAD) to incubation media and various lengths of incubations. Treatment of the epithelium and muscle of the guinea-pig seminal vesicle with NAD elicited a shift from normal reductive metabolism of testosterone toward oxidative metabolism. This shift toward oxidative metabolism of testosterone was particularly marked in the muscle of the guinea-pig seminal vesicle. Ovine prolactin was highly effective in inhibiting the reductive metabolism of testosterone by the sex accessory organs. This effect appeared primarily as a decrease in dihydrotestosterone formation and was noted in both the presence and absence of NADPH or NAD. Oxidized metabolites, androstenedione and androstandione, were apparently insensitive to prolactin treatment in vitro. Variations induced by prolactin in the concentrations of intracellular androgens may be important in either the normal or abnormal growth and function of male sex accessory organs."}
{"id": "PMID:235638", "title": "Increased running response to morphine in morphine-pretreated mice.", "content": "The running response of B6AF1/J mice to 25 mg/kg of morphine sulfate was increased up to 3-fold when this dose was administered either twice daily for 5 days or once a week for 2 or 3 weeks. The effect of weekly pretreatment was proportional to the dose of morphine and lasted as long as 1 month after pretreatment was stopped. There was no sensitization when the mice were less than 15 days old at the time of pretreatment. Of the parental strains, untreated C57Bl/6J mice showed a good running response to morphine, while A/J mice showed little response. Pretreatment of either of these strains produced only slight sensitization. Pretreatment of the hybrids with levorphanol increased the response to morphine. Dextrorphan and naloxone were ineffective. Sensitization by morphine was blocked by naloxone. Increased morphine running was not associated with analgesic tolerance as measured by the tail-flick assay. Morphine pretreatment produced some increase in the running response to amphetamine and to cocaine. Pretreatment with amphetamine or cocaine did not increase the response to morphine.", "contents": "Increased running response to morphine in morphine-pretreated mice. The running response of B6AF1/J mice to 25 mg/kg of morphine sulfate was increased up to 3-fold when this dose was administered either twice daily for 5 days or once a week for 2 or 3 weeks. The effect of weekly pretreatment was proportional to the dose of morphine and lasted as long as 1 month after pretreatment was stopped. There was no sensitization when the mice were less than 15 days old at the time of pretreatment. Of the parental strains, untreated C57Bl/6J mice showed a good running response to morphine, while A/J mice showed little response. Pretreatment of either of these strains produced only slight sensitization. Pretreatment of the hybrids with levorphanol increased the response to morphine. Dextrorphan and naloxone were ineffective. Sensitization by morphine was blocked by naloxone. Increased morphine running was not associated with analgesic tolerance as measured by the tail-flick assay. Morphine pretreatment produced some increase in the running response to amphetamine and to cocaine. Pretreatment with amphetamine or cocaine did not increase the response to morphine."}
{"id": "PMID:235639", "title": "Further properties of stereospecific opiate binding sites in rat brain: on the nature of the sodium effect.", "content": "Addition of sodium salts has been reported to enhance stereospecific binding of opiate antagonists while reducing binding of agonists to rat brain homogenate. We have tested, in addition to sodium and potassium, a number of organic cations. Our results support the suggestion that the ability to enhace antagonist binding is not a general characteristic of cations or high ionic strength, but a property of sodium ions. We have shown that the increase in antagonist binding results from an enhancement of binding affinity and not from unmasking of new binding sites. The reduction in etorphine binding in the presence of sodium is due to a decrease in binding affinity. This decrease is largely accounted for by an acceleration in the dissociation rate, while the greater affinity of naltrexone binding appears to be due to an increase in rate of association. Our results are consistent with the hypothesis of a conformational change in opiate binding sites in the presence of sodium, transformed sites exhibiting greater affinity for antagonists and reduced affinity for agonists. Preheating of rat brain P2 fraction at 50 degrees C results in gradual inactivation of stereospecific binding, but an increase in naltrexone binding is consistently observed after heating at 50 degrees C for 2 to 3 minutes, even at optimal concentrations of sodium.", "contents": "Further properties of stereospecific opiate binding sites in rat brain: on the nature of the sodium effect. Addition of sodium salts has been reported to enhance stereospecific binding of opiate antagonists while reducing binding of agonists to rat brain homogenate. We have tested, in addition to sodium and potassium, a number of organic cations. Our results support the suggestion that the ability to enhace antagonist binding is not a general characteristic of cations or high ionic strength, but a property of sodium ions. We have shown that the increase in antagonist binding results from an enhancement of binding affinity and not from unmasking of new binding sites. The reduction in etorphine binding in the presence of sodium is due to a decrease in binding affinity. This decrease is largely accounted for by an acceleration in the dissociation rate, while the greater affinity of naltrexone binding appears to be due to an increase in rate of association. Our results are consistent with the hypothesis of a conformational change in opiate binding sites in the presence of sodium, transformed sites exhibiting greater affinity for antagonists and reduced affinity for agonists. Preheating of rat brain P2 fraction at 50 degrees C results in gradual inactivation of stereospecific binding, but an increase in naltrexone binding is consistently observed after heating at 50 degrees C for 2 to 3 minutes, even at optimal concentrations of sodium."}
{"id": "PMID:235640", "title": "Effects of dopamine on carotid chemo- and baroreceptors in vitro.", "content": "1. The effects of dopamine on the sensory discharges originating from arterial chemo- and baroreceptors were studied in vitro using carotid bodies or sinuses excised from anaesthetized cats and superfused with Locke's solution. 2. Intrastream injections of dopamine 10-200 mug produced a transient depression of the frequency of chemoreceptor discharges. This effect was observed in response to the first injection in eighteen out of twenty preparations. 3. The inhibitory effect of dopamine can counteract partially or totally the excitation of chemoreceptors evoked by simultaneous application of acetylcholine or cyanide. 4. This inhibitory effect of dopamine is reduced or abolished by pretreatment with dopaminergic (Spiroperidol) or alpha-adrenergic (Dibenamine) blockers. 5. In response to repeated injections of dopamine applied at short intervals, the inhibitory effect is replaced by a biphasic effect (early inhibition followed by late excitation), a late and long-lasting excitation or no changes in chemoreceptor activity. The late excitatory effects of dopamine are not blocked by dopaminergic or alpha-adrenergic blockers. 6. Noradrenaline does not affect the chemoreceptor activity of the superfused carotid body. DL-DOPA induces only a late and long-lasting excitatory effect. 7. In carotid sinus preparations, dopamine induces a weak but long-lasting increase in the frequency of baroreceptor discharges. 8. It is concluded that dopamine may play a modulatory role in the generation of chemoreceptor activity through local regulatory processes.", "contents": "Effects of dopamine on carotid chemo- and baroreceptors in vitro. 1. The effects of dopamine on the sensory discharges originating from arterial chemo- and baroreceptors were studied in vitro using carotid bodies or sinuses excised from anaesthetized cats and superfused with Locke's solution. 2. Intrastream injections of dopamine 10-200 mug produced a transient depression of the frequency of chemoreceptor discharges. This effect was observed in response to the first injection in eighteen out of twenty preparations. 3. The inhibitory effect of dopamine can counteract partially or totally the excitation of chemoreceptors evoked by simultaneous application of acetylcholine or cyanide. 4. This inhibitory effect of dopamine is reduced or abolished by pretreatment with dopaminergic (Spiroperidol) or alpha-adrenergic (Dibenamine) blockers. 5. In response to repeated injections of dopamine applied at short intervals, the inhibitory effect is replaced by a biphasic effect (early inhibition followed by late excitation), a late and long-lasting excitation or no changes in chemoreceptor activity. The late excitatory effects of dopamine are not blocked by dopaminergic or alpha-adrenergic blockers. 6. Noradrenaline does not affect the chemoreceptor activity of the superfused carotid body. DL-DOPA induces only a late and long-lasting excitatory effect. 7. In carotid sinus preparations, dopamine induces a weak but long-lasting increase in the frequency of baroreceptor discharges. 8. It is concluded that dopamine may play a modulatory role in the generation of chemoreceptor activity through local regulatory processes."}
{"id": "PMID:235643", "title": "The isolation and characterization of lactoferrin from sow milk and boar seminal plasma.", "content": "Lactoferrin isolated from sow milk (about 0-6 mg/ml) was shown to be chromatographically homogeneous, an observation supported by electrophoresis and by reaction against monospecific anti-lactoferrin antiserum. Isoelectric focusing showed multiple forms of the protein (i.e.p., 9-3 to 10-0) converted by neuraminidase to one form (i.e.p., 9-65). Boar seminal plasma contains immunologically identical lactoferrin (0-1 to 0-5 mg/ml) which binds strongly to boar spermatozoa.", "contents": "The isolation and characterization of lactoferrin from sow milk and boar seminal plasma. Lactoferrin isolated from sow milk (about 0-6 mg/ml) was shown to be chromatographically homogeneous, an observation supported by electrophoresis and by reaction against monospecific anti-lactoferrin antiserum. Isoelectric focusing showed multiple forms of the protein (i.e.p., 9-3 to 10-0) converted by neuraminidase to one form (i.e.p., 9-65). Boar seminal plasma contains immunologically identical lactoferrin (0-1 to 0-5 mg/ml) which binds strongly to boar spermatozoa."}
{"id": "PMID:235644", "title": "Cardioselective beta-adrenergic blocking agents. 1. 1-((3,4-Dimethoxyphenethyl)amino)-3-aryloxy-2-propanols.", "content": "A series of 1-amino-3-aryloxy-2-propanols has been synthesized and examined for cardioselective beta-blockade. The introduction of the (3,4-dimethoxyphenethyl)amino group lead to the most cardioselective agents. Structure-activity relationships are discussed. Of the compounds tested 1-[(3,4-dimethoxyphenethyl)amino]-3-(m-tolyloxy)-2-propanol was selected for clinical trial because of optimal potency and selectivity.", "contents": "Cardioselective beta-adrenergic blocking agents. 1. 1-((3,4-Dimethoxyphenethyl)amino)-3-aryloxy-2-propanols. A series of 1-amino-3-aryloxy-2-propanols has been synthesized and examined for cardioselective beta-blockade. The introduction of the (3,4-dimethoxyphenethyl)amino group lead to the most cardioselective agents. Structure-activity relationships are discussed. Of the compounds tested 1-[(3,4-dimethoxyphenethyl)amino]-3-(m-tolyloxy)-2-propanol was selected for clinical trial because of optimal potency and selectivity."}
{"id": "PMID:235646", "title": "Substituted thiadiazolines as inhibitors of central nervous system carbonic anhydrase.", "content": "A series (24-30) of substituted thiadiazolines was synthesized and tested for in vitro carbonic anhydrase inhibition and for protective ability against pentylenetetrazole-induced convulsions. ED50 (pentylenetetrazole protection), TD50, and LD50 values are reported for each compound. With the exception of 30, all compounds approximated the model compound methazolamide as in vitro carbonic anhydrase inhibitors. Several of the compounds produced extended protection against pentylenetetrazole-induced convulsions. Ring methoxy substitution in the ortho position appeared to produce maximum activity.", "contents": "Substituted thiadiazolines as inhibitors of central nervous system carbonic anhydrase. A series (24-30) of substituted thiadiazolines was synthesized and tested for in vitro carbonic anhydrase inhibition and for protective ability against pentylenetetrazole-induced convulsions. ED50 (pentylenetetrazole protection), TD50, and LD50 values are reported for each compound. With the exception of 30, all compounds approximated the model compound methazolamide as in vitro carbonic anhydrase inhibitors. Several of the compounds produced extended protection against pentylenetetrazole-induced convulsions. Ring methoxy substitution in the ortho position appeared to produce maximum activity."}
{"id": "PMID:235652", "title": "Clinical and ultrastructural observations in a kindred with normo-hyperkalaemic periodic paralysis.", "content": "Electron microscopic studies of muscle biopsies from clinically unaffected sibs in a family with normo-hyperkalaemic periodic paralysis with variable myotonia have revealed dilatation of the sarcoplasmic reticulum similar to that observed in affected members. This supports the view that such dilatation is not only a significant and likely primary ultrastructural change but that it may precede clinical manifestations and represent an anatomical marker of the genetic trait. Identical dilatation of the sarcoplasmic reticulum was found in the clinically unaffected father of the affected and unaffected grandchildren of the propositus. This raises the possibility that this non-consanguineous member contributed to the genetic trait or its manifestations in the grandchildren of the index patient since similar dilatation of the sarcoplasmic reticulum was not observed in the muscles of healthy control subjects.", "contents": "Clinical and ultrastructural observations in a kindred with normo-hyperkalaemic periodic paralysis. Electron microscopic studies of muscle biopsies from clinically unaffected sibs in a family with normo-hyperkalaemic periodic paralysis with variable myotonia have revealed dilatation of the sarcoplasmic reticulum similar to that observed in affected members. This supports the view that such dilatation is not only a significant and likely primary ultrastructural change but that it may precede clinical manifestations and represent an anatomical marker of the genetic trait. Identical dilatation of the sarcoplasmic reticulum was found in the clinically unaffected father of the affected and unaffected grandchildren of the propositus. This raises the possibility that this non-consanguineous member contributed to the genetic trait or its manifestations in the grandchildren of the index patient since similar dilatation of the sarcoplasmic reticulum was not observed in the muscles of healthy control subjects."}
{"id": "PMID:235653", "title": "Effect of electric fields on light-scattering and fluorescence of chromaffin granules.", "content": "Electric field pulses (in the 5 to 25 kV/cm range) were found to cause a transient increase in the intensity of scattered light (wavelength equals 369 nm, scattering angle equals 90 degrees) from aqueous sucrose suspensions of chromaffin granules. Similar observations were made with the membranes of osmotically lysed chromaffin granules. Under the same experimental conditions the degree of polarization of the scattered light changed only very slightly. The fluorescence of the hydrophobic probe diphenyl-hexatriene, incorporated into the membrane of intact chromaffin granules, showed similar transient changes in the intensity. The calculated relaxation times for these changes in optical properties were approximately 150 musec for the rising phase, and approximately 1 msec for the early stage of the decay. A further relaxation time of about 30 msec was also observed by using this probe. Essentially, all of these signals originated from the granule membrane, and could be attributed to rather small changes in particle size, membrane thickness or refractive index. Moreover, these signals were found to be completely reversible. Catecholamine release from intact granules, pulsed at voltages of 25 kV/cm, occurs already during the first few milliseconds of the transient membrane change.", "contents": "Effect of electric fields on light-scattering and fluorescence of chromaffin granules. Electric field pulses (in the 5 to 25 kV/cm range) were found to cause a transient increase in the intensity of scattered light (wavelength equals 369 nm, scattering angle equals 90 degrees) from aqueous sucrose suspensions of chromaffin granules. Similar observations were made with the membranes of osmotically lysed chromaffin granules. Under the same experimental conditions the degree of polarization of the scattered light changed only very slightly. The fluorescence of the hydrophobic probe diphenyl-hexatriene, incorporated into the membrane of intact chromaffin granules, showed similar transient changes in the intensity. The calculated relaxation times for these changes in optical properties were approximately 150 musec for the rising phase, and approximately 1 msec for the early stage of the decay. A further relaxation time of about 30 msec was also observed by using this probe. Essentially, all of these signals originated from the granule membrane, and could be attributed to rather small changes in particle size, membrane thickness or refractive index. Moreover, these signals were found to be completely reversible. Catecholamine release from intact granules, pulsed at voltages of 25 kV/cm, occurs already during the first few milliseconds of the transient membrane change."}
{"id": "PMID:235654", "title": "The reaction of chemical probes with the erythrocyte membrane.", "content": "Trinitrobenzenesulfonate (TNBS), fluorodinitrobenzene (FDNB) and suberimidate have been reacted with intact human erythrocytes. TNBS does not penetrate the cell membrane significantly at 23 degrees C in bicarbonate-NaCl buffer, pH 8.6, as estimated by the labeling of the N-terminal valine of hemoglobin. Hence, under these conditions it can be used as a vectorial probe. However, at 37 degrees C, especially in phosphate buffer, at pH 8.6, TNBS does penetrate the cell membrane. FDNB and suberimidate both penetrate the erythrocyte membrane. The time course reaction of TNBS with intact erythrocytes over a 24-hr period at 23 degrees C is complex and shows transition zones for both membrane phosphatidylethanolamine (PE) and membrane proteins. No significant cell lysis occurs up to 10 hr. The fraction of total PE or phosphatidylserine (PS) which reacts with TNBS by this time period can be considered to be located on the outer surface of the cell membrane. Under these conditions it can be located on the outer surface of the cell membrane. Under these conditions it can be shown that 10 to 20% of the total PE and no PS is located on the outer surface of the membrane and hence these amino phospholipids are asymmetrically arranged. The pH gradient between the inside and outside of the cell in our system is 0.4 pH units. Nigericin has no effect on the extent of labeling of PE or PS by TNBS. Isotonic sucrose gives a slight enhancement of the labeling of PE by TNBS. Hence, the inability of PE and PS to react with the TNBS is considered not due to the inside of the cell having a lower pH. The extent of reaction of TNBS with PE is not influenced by changing the osmolarity of the medium or by treatment of cells with pronase, trypsin, phospholipase A or phospholipase D. However, bovine serum albumin (BSA) does protect some of the PE molecules from reacting with TNBS. Cels treated with suberimidate were suspended in either isotonic NaCl or in distilled water. In both cases the suberimidate-treated cells became refractory to hypotonic lysis. Pretreatment of cells with TNBS did not prevent them from interacting with suberimidate and becoming refractory to lysis. However, pretreatment of cells with the penetrating probe FDNB abolished the suberimidate effect. Electron-microscopic analysis of the cells showed a continuous membrane in the case of cells suspended in isotonic saline. The cells suspended in water did not lyse but their membranes had many large holes, sufficient to let the hemoglobin leak out. Since the hemoglobin did not leak out we know that the hemoglobin is cross-linked into a large supramolecular aggregate.", "contents": "The reaction of chemical probes with the erythrocyte membrane. Trinitrobenzenesulfonate (TNBS), fluorodinitrobenzene (FDNB) and suberimidate have been reacted with intact human erythrocytes. TNBS does not penetrate the cell membrane significantly at 23 degrees C in bicarbonate-NaCl buffer, pH 8.6, as estimated by the labeling of the N-terminal valine of hemoglobin. Hence, under these conditions it can be used as a vectorial probe. However, at 37 degrees C, especially in phosphate buffer, at pH 8.6, TNBS does penetrate the cell membrane. FDNB and suberimidate both penetrate the erythrocyte membrane. The time course reaction of TNBS with intact erythrocytes over a 24-hr period at 23 degrees C is complex and shows transition zones for both membrane phosphatidylethanolamine (PE) and membrane proteins. No significant cell lysis occurs up to 10 hr. The fraction of total PE or phosphatidylserine (PS) which reacts with TNBS by this time period can be considered to be located on the outer surface of the cell membrane. Under these conditions it can be located on the outer surface of the cell membrane. Under these conditions it can be shown that 10 to 20% of the total PE and no PS is located on the outer surface of the membrane and hence these amino phospholipids are asymmetrically arranged. The pH gradient between the inside and outside of the cell in our system is 0.4 pH units. Nigericin has no effect on the extent of labeling of PE or PS by TNBS. Isotonic sucrose gives a slight enhancement of the labeling of PE by TNBS. Hence, the inability of PE and PS to react with the TNBS is considered not due to the inside of the cell having a lower pH. The extent of reaction of TNBS with PE is not influenced by changing the osmolarity of the medium or by treatment of cells with pronase, trypsin, phospholipase A or phospholipase D. However, bovine serum albumin (BSA) does protect some of the PE molecules from reacting with TNBS. Cels treated with suberimidate were suspended in either isotonic NaCl or in distilled water. In both cases the suberimidate-treated cells became refractory to hypotonic lysis. Pretreatment of cells with TNBS did not prevent them from interacting with suberimidate and becoming refractory to lysis. However, pretreatment of cells with the penetrating probe FDNB abolished the suberimidate effect. Electron-microscopic analysis of the cells showed a continuous membrane in the case of cells suspended in isotonic saline. The cells suspended in water did not lyse but their membranes had many large holes, sufficient to let the hemoglobin leak out. Since the hemoglobin did not leak out we know that the hemoglobin is cross-linked into a large supramolecular aggregate."}
{"id": "PMID:235660", "title": "Cardiac lesions in collagen disease.", "content": "Clinical and pathological abnormalities of the heart that may have major functional significance in those conditions were studied in collagen disease (total 242 cases). 1. atypical verrucous endocarditis (Libmann-Sacks) were found in 2 cases with loupus erythematosus (25 cases) and in 1 case with scleroderma (3 cases). 2. Rheumatoid nodules were not seen in the heart of rheumatoid arthritis patients (9 cases). 3. The most frequent findings in the heart with collagen diseases were pericarditis, fibrous scarring of the heart muscle, focal inflammation and vasculitis is similar to periarteritis nodosa or endoarteritis obliterans. 4. Morphological changes of the A-V node were found in patients who had A-V dissociation or A-V block before death. Heart muscle infarctions were found in 2 cases.", "contents": "Cardiac lesions in collagen disease. Clinical and pathological abnormalities of the heart that may have major functional significance in those conditions were studied in collagen disease (total 242 cases). 1. atypical verrucous endocarditis (Libmann-Sacks) were found in 2 cases with loupus erythematosus (25 cases) and in 1 case with scleroderma (3 cases). 2. Rheumatoid nodules were not seen in the heart of rheumatoid arthritis patients (9 cases). 3. The most frequent findings in the heart with collagen diseases were pericarditis, fibrous scarring of the heart muscle, focal inflammation and vasculitis is similar to periarteritis nodosa or endoarteritis obliterans. 4. Morphological changes of the A-V node were found in patients who had A-V dissociation or A-V block before death. Heart muscle infarctions were found in 2 cases."}
{"id": "PMID:235662", "title": "[Reaction of the neurosecretory system of dogs with reno-vascular hypertension in the postnatal ontogenesis].", "content": "In dogs of different age with simulated renovascular hypertension neurosecretion of the hypothalamo-neurohypophysial system was studied. Experiments were conducted with puppies 18-22 days, 11/2-3 months and dogs 3-5 years old. It was established that in the ontogenesis of dogs the differentiation of neurons in the supraoptic nucleus occurred earlier than that of cells in the paraventricular nucleus. The simulation of hypertension accelerates the differentiation of tbe neurosecretory cells. The development of arterial hypertension leads to prevalence of precesses of the neurosecretory material outflow over the latter's synthesis, irrespective of the maturity of the neurosecretory system. With the arterial pressure stabilized at a high level a concordance between an elevated synthesis of the neurosecretion and its increased outflow is noted. Visual evaluation of the activity is supported by the results of cellular micrometry.", "contents": "[Reaction of the neurosecretory system of dogs with reno-vascular hypertension in the postnatal ontogenesis]. In dogs of different age with simulated renovascular hypertension neurosecretion of the hypothalamo-neurohypophysial system was studied. Experiments were conducted with puppies 18-22 days, 11/2-3 months and dogs 3-5 years old. It was established that in the ontogenesis of dogs the differentiation of neurons in the supraoptic nucleus occurred earlier than that of cells in the paraventricular nucleus. The simulation of hypertension accelerates the differentiation of tbe neurosecretory cells. The development of arterial hypertension leads to prevalence of precesses of the neurosecretory material outflow over the latter's synthesis, irrespective of the maturity of the neurosecretory system. With the arterial pressure stabilized at a high level a concordance between an elevated synthesis of the neurosecretion and its increased outflow is noted. Visual evaluation of the activity is supported by the results of cellular micrometry."}
{"id": "PMID:235663", "title": "[Problem of increasing the viability of the ischemic myocardium in the light of experimental studies].", "content": "With the author's own observations and literature sources as a background the key issues concerned with increasing the viability of the myocardium in acute ischemia are considered. The possibility of a material enlargement of the collateral coronary circulation through administration of mesatonemonoaminoxidase inhibitors, diprazine, preparations of the metabolites type and of other agents is shown. Under consideration are data on the membranes-stabilizing effect in acute ischemia of the myocardium of dimedrol, diprazine and prednisolone, as well as possible ways of increasing the survival of the myocardium by activating the redox-processes and through an adequate supply of energy to ensure the vital functions of the myocardial cell at rest by using pertinent pharmacological agents (cytochrome C, NADP, ubiquinone, hexose-phosphate, monoaminodicarboxylic amino acids).", "contents": "[Problem of increasing the viability of the ischemic myocardium in the light of experimental studies]. With the author's own observations and literature sources as a background the key issues concerned with increasing the viability of the myocardium in acute ischemia are considered. The possibility of a material enlargement of the collateral coronary circulation through administration of mesatonemonoaminoxidase inhibitors, diprazine, preparations of the metabolites type and of other agents is shown. Under consideration are data on the membranes-stabilizing effect in acute ischemia of the myocardium of dimedrol, diprazine and prednisolone, as well as possible ways of increasing the survival of the myocardium by activating the redox-processes and through an adequate supply of energy to ensure the vital functions of the myocardial cell at rest by using pertinent pharmacological agents (cytochrome C, NADP, ubiquinone, hexose-phosphate, monoaminodicarboxylic amino acids)."}
{"id": "PMID:235665", "title": "Effect of diphosphonate on crystallization of calcium oxalate in vitro.", "content": "Reliable techniques for the calculation of activity product (state of saturation), formation product (limit of metastability) and crystal growth of calcium oxalate were devised.  The activity product at saturation was 2.53 times 10 minus 9 M2, and was independent of duration of incubation, solid-to-solution ratio, pH, calcium concentration or ionic strength. These tehcniques were utilized to assess the effect of disodium ethane-1-hydroxy-1, 1-diphosphonate (EHDP) on crystallization of calcium oxalate in an aqueous salt solution in vitro. EHDP increased the formation product of calcium oxalate, indicating an inhibition of nucleation of calcium oxalate. Further, it inhibited the crystal growth of calcium oxalate.", "contents": "Effect of diphosphonate on crystallization of calcium oxalate in vitro. Reliable techniques for the calculation of activity product (state of saturation), formation product (limit of metastability) and crystal growth of calcium oxalate were devised.  The activity product at saturation was 2.53 times 10 minus 9 M2, and was independent of duration of incubation, solid-to-solution ratio, pH, calcium concentration or ionic strength. These tehcniques were utilized to assess the effect of disodium ethane-1-hydroxy-1, 1-diphosphonate (EHDP) on crystallization of calcium oxalate in an aqueous salt solution in vitro. EHDP increased the formation product of calcium oxalate, indicating an inhibition of nucleation of calcium oxalate. Further, it inhibited the crystal growth of calcium oxalate."}
{"id": "PMID:235666", "title": "Dailysate calcium and plasma calcium fractions during and after haemodialysis.", "content": "Dialysate calcium and plasma calcium fractions during and after haemodialysis: The effect of differenct dialysate Ca concentrations on the plasma Ca fractions was examined in 28 patients. In 10 patients dialysed with a dialysate Ca concentration of 3.0 mEq/l the Ca fractions were determined at the start and end of dialysis. 8 patients were dialysed with dialysate with dialysate Ca of 3.5 mEq/l. In this group the Ca fractions were also estimated in the dialysis-free interval. The third group was dialysed with a dialysate Ca of 4.5 mEq/l. Total calcium and protein-bound calcium rose significantly in all groups. Ionised calcium in the first group was significantly reduced, in the second group it remained constant and in the third group it was significantly raised. Since parathyroid function  depends on the plasma ionised calcium it is concluded that a dialysed concentration of 3.0 mEq/l is partly responsible for the pathogenesis of secondary hyperparathyroidism and of renal osteodystophy. In normocalcaemic patients a dialysate Ca concentration of 3.5 to 4.0 mEq/l is optimal. In patients entering long-term haemodialysis treatment with pronounced calcium deficiency symptoms a dialysate Ca of up to 4.5 mEq/l may be indicated for a short period after having normalized the inorganic phosphate levels in order to prevent extraosseous calcification.", "contents": "Dailysate calcium and plasma calcium fractions during and after haemodialysis. Dialysate calcium and plasma calcium fractions during and after haemodialysis: The effect of differenct dialysate Ca concentrations on the plasma Ca fractions was examined in 28 patients. In 10 patients dialysed with a dialysate Ca concentration of 3.0 mEq/l the Ca fractions were determined at the start and end of dialysis. 8 patients were dialysed with dialysate with dialysate Ca of 3.5 mEq/l. In this group the Ca fractions were also estimated in the dialysis-free interval. The third group was dialysed with a dialysate Ca of 4.5 mEq/l. Total calcium and protein-bound calcium rose significantly in all groups. Ionised calcium in the first group was significantly reduced, in the second group it remained constant and in the third group it was significantly raised. Since parathyroid function  depends on the plasma ionised calcium it is concluded that a dialysed concentration of 3.0 mEq/l is partly responsible for the pathogenesis of secondary hyperparathyroidism and of renal osteodystophy. In normocalcaemic patients a dialysate Ca concentration of 3.5 to 4.0 mEq/l is optimal. In patients entering long-term haemodialysis treatment with pronounced calcium deficiency symptoms a dialysate Ca of up to 4.5 mEq/l may be indicated for a short period after having normalized the inorganic phosphate levels in order to prevent extraosseous calcification."}
{"id": "PMID:235667", "title": "Angiotensin stimulated AVP-release in humans.", "content": "Release of arginine vasopressin (AVP) from rat neurohypophysis in in vitro studies is significantly augmented by the addition of angiotensin (A-II), and in in vivo studies in dogs renin and A-II were found to stimulate secretion of AVP. Both these results suggest the existence of a direct relationship between the salt regulating renin-angiotensin-aldosterone system and the water controlling AVP system. To evaluate whether such observations apply also in man a sensitive double antibody radioimmunoassay for AVP was developed [17, 18]. Basal plasma levels of AVP in recumbent humans without salt and fluid restriction at room temperature were 3.4 plus or minus 2.2 pg/ml, and 30 min after the onset of an A-II infusion at a concentration of 3-30 ng/min-kg, a significant increase of AVP was found. Maximum  measurements were 2-5 times basal levels which returned to normal within 90 min. During the A-II infusion one also noted a 20 mm Hg rise in blood pressure, accompanied by a significant decrease in plasma renin activity. During the same period serum osmolality and serum sodium concentration did not change. Elevation of blood pressure by norepinephrine was not followed by any detectable change of plasma AVP levels, thus excluding a nonspecific blood pressure effect.", "contents": "Angiotensin stimulated AVP-release in humans. Release of arginine vasopressin (AVP) from rat neurohypophysis in in vitro studies is significantly augmented by the addition of angiotensin (A-II), and in in vivo studies in dogs renin and A-II were found to stimulate secretion of AVP. Both these results suggest the existence of a direct relationship between the salt regulating renin-angiotensin-aldosterone system and the water controlling AVP system. To evaluate whether such observations apply also in man a sensitive double antibody radioimmunoassay for AVP was developed [17, 18]. Basal plasma levels of AVP in recumbent humans without salt and fluid restriction at room temperature were 3.4 plus or minus 2.2 pg/ml, and 30 min after the onset of an A-II infusion at a concentration of 3-30 ng/min-kg, a significant increase of AVP was found. Maximum  measurements were 2-5 times basal levels which returned to normal within 90 min. During the A-II infusion one also noted a 20 mm Hg rise in blood pressure, accompanied by a significant decrease in plasma renin activity. During the same period serum osmolality and serum sodium concentration did not change. Elevation of blood pressure by norepinephrine was not followed by any detectable change of plasma AVP levels, thus excluding a nonspecific blood pressure effect."}
{"id": "PMID:235668", "title": "[Determination of the ammonia content in the atmosphere of biosatellite mock-ups and approaches to its standardization].", "content": "The concentrations of ammonia having an irritating and acute effect on intact rats and hypokinetic rats were determined. The thresholds of the chronic effect were calculated for each group of animals. The 30-day hypokinesia increased the animal sensitivity to ammonia: the threshold of the irritating effect decreased twice. The atmosphere in an enclosure equipped with an automatic life support system was examined during 30-day integrated animal experiments. Ammonia proved to be the major contaminant. Its concentration increased gradually, remaining for the longest part of the experiments (28 days) below the threshold of the chronic effect (40 mg/m3).", "contents": "[Determination of the ammonia content in the atmosphere of biosatellite mock-ups and approaches to its standardization]. The concentrations of ammonia having an irritating and acute effect on intact rats and hypokinetic rats were determined. The thresholds of the chronic effect were calculated for each group of animals. The 30-day hypokinesia increased the animal sensitivity to ammonia: the threshold of the irritating effect decreased twice. The atmosphere in an enclosure equipped with an automatic life support system was examined during 30-day integrated animal experiments. Ammonia proved to be the major contaminant. Its concentration increased gradually, remaining for the longest part of the experiments (28 days) below the threshold of the chronic effect (40 mg/m3)."}
{"id": "PMID:235669", "title": "[Toxicological evaluation of ethyl acetate in conditions of sealed cabin atmospheres].", "content": "Ethyl acetate was studied as an atmosphere contaminant in an enclosed environment. A 90-day continuous experiment on 160 white rats and 120 white mice with three concentrations of the compound (43, 10 and 2 mg/m3) was carried out. Ethyl acetate used in the first two concentrations caused functional disturbances in the state of animals and morphological changes in their viscera. Ethyl acetate at a concentration of 2 mg/m3 was ineffective. The data obtained allow recommendations of permissible concentrations of ethyl acetate vapours in an enclosed atmosphere in relation to a different time of man's exposure.", "contents": "[Toxicological evaluation of ethyl acetate in conditions of sealed cabin atmospheres]. Ethyl acetate was studied as an atmosphere contaminant in an enclosed environment. A 90-day continuous experiment on 160 white rats and 120 white mice with three concentrations of the compound (43, 10 and 2 mg/m3) was carried out. Ethyl acetate used in the first two concentrations caused functional disturbances in the state of animals and morphological changes in their viscera. Ethyl acetate at a concentration of 2 mg/m3 was ineffective. The data obtained allow recommendations of permissible concentrations of ethyl acetate vapours in an enclosed atmosphere in relation to a different time of man's exposure."}
{"id": "PMID:235674", "title": "Production and consumption of alcoholic beverages in the USSR. A statistical study.", "content": "The Soviet government has published few official statistics on alcoholic beverages. Using Soviet statistical, commerical and technical sources, however, estimates can be derived on the production and consumption of alcoholic beverages during the 1957-71 period, including urban and rural consumption, expenditures, tax revenues, imports and exports and use of agricultural products.", "contents": "Production and consumption of alcoholic beverages in the USSR. A statistical study. The Soviet government has published few official statistics on alcoholic beverages. Using Soviet statistical, commerical and technical sources, however, estimates can be derived on the production and consumption of alcoholic beverages during the 1957-71 period, including urban and rural consumption, expenditures, tax revenues, imports and exports and use of agricultural products."}
{"id": "PMID:235675", "title": "Drinking attitudes and practices among Wind River Reservation Indian youth.", "content": "The attitudes toward drinking of a cohort of 7th- and 8th-grade American Indians, mostly Arapahoe and Shoshone, living on Wyoming's Wing River Reservation were studied. The data suggest that these adolescents and their peers both approve of drinking and do drink even though they can get into trouble for illegal alcohol use.", "contents": "Drinking attitudes and practices among Wind River Reservation Indian youth. The attitudes toward drinking of a cohort of 7th- and 8th-grade American Indians, mostly Arapahoe and Shoshone, living on Wyoming's Wing River Reservation were studied. The data suggest that these adolescents and their peers both approve of drinking and do drink even though they can get into trouble for illegal alcohol use."}
{"id": "PMID:235676", "title": "Attitudes toward alcohol and alcoholism among professionals and nonprofessionals.", "content": "Analysis of the responses of graduate students, professional social service agency workers and community residents to scales measuring attitudes and beliefs about alcohol and alcoholism suggests that the professionals tend to reflect the opinions and biases of the community within which they work. The results are discussed in terms of the usefulness of the multidimensional model of attitude structure for comparing attitudes among various groups and the implications for professional and community education programs.", "contents": "Attitudes toward alcohol and alcoholism among professionals and nonprofessionals. Analysis of the responses of graduate students, professional social service agency workers and community residents to scales measuring attitudes and beliefs about alcohol and alcoholism suggests that the professionals tend to reflect the opinions and biases of the community within which they work. The results are discussed in terms of the usefulness of the multidimensional model of attitude structure for comparing attitudes among various groups and the implications for professional and community education programs."}
{"id": "PMID:235677", "title": "Relationship between treatment facilities and prevalence of alcoholism and drug abuse.", "content": "Data are presented which suggest that, in the Commonwealth of Pennsylvania, the availability of treatment of drug abuse and alcoholism is inversely related to the prevalence of the problems. It is hypothesized that as the treatment response to one increases, the treatment response to the other declines. Some of the possible causes and consequences are outlined.", "contents": "Relationship between treatment facilities and prevalence of alcoholism and drug abuse. Data are presented which suggest that, in the Commonwealth of Pennsylvania, the availability of treatment of drug abuse and alcoholism is inversely related to the prevalence of the problems. It is hypothesized that as the treatment response to one increases, the treatment response to the other declines. Some of the possible causes and consequences are outlined."}
{"id": "PMID:235678", "title": "Glucose intolerance in alcoholism.", "content": "Intravenous glucose tolerance tests were given to 31 nondiabetic alcoholics and 11 healthy nonalcoholic controls. In almost half of the alcoholics peak glucose concentration was higher and glucose elimination from the plasma was slower than in the controls.", "contents": "Glucose intolerance in alcoholism. Intravenous glucose tolerance tests were given to 31 nondiabetic alcoholics and 11 healthy nonalcoholic controls. In almost half of the alcoholics peak glucose concentration was higher and glucose elimination from the plasma was slower than in the controls."}
{"id": "PMID:235670", "title": "[Preservation of food wastes by a mixture of quinosol and salicyclic acid].", "content": "A 90-day experiment has shown that a number of toxic gaseous contaminants are released into the atmosphere as a result of storage of mixed food wastes. The microorganisms dwelling upon decaving food wastes include different microbial species from the environment and food products. A preserving agent consisting of a mixture of quinosole and salicylic acid (1:1) has been used. The agent inhibited microbial activity and terminated processes of decay. This was indicated by a decline in the concentration of ammonia and amine compounds. In the presence of the agent fermentation processes, on the contrary, continued and increased.", "contents": "[Preservation of food wastes by a mixture of quinosol and salicyclic acid]. A 90-day experiment has shown that a number of toxic gaseous contaminants are released into the atmosphere as a result of storage of mixed food wastes. The microorganisms dwelling upon decaving food wastes include different microbial species from the environment and food products. A preserving agent consisting of a mixture of quinosole and salicylic acid (1:1) has been used. The agent inhibited microbial activity and terminated processes of decay. This was indicated by a decline in the concentration of ammonia and amine compounds. In the presence of the agent fermentation processes, on the contrary, continued and increased."}
{"id": "PMID:235679", "title": "Treatment outcome in a drinking-decisions program.", "content": "Of 98 alcoholics who were free to decide whether or not to drink during a 6-week inpatient treatment program, 55 chose to drink. The nondrinkers tended to show more improvement at a 6-month follow-up than did the drinkers.", "contents": "Treatment outcome in a drinking-decisions program. Of 98 alcoholics who were free to decide whether or not to drink during a 6-week inpatient treatment program, 55 chose to drink. The nondrinkers tended to show more improvement at a 6-month follow-up than did the drinkers."}
{"id": "PMID:235680", "title": "Intellectual competence of alcoholics.", "content": "Alcoholic and psychiatric inpatients matched in age and education performed comparably on a battery of cognitive tests. The absence of impairment in the alcoholics is attributed to the relatively short duration of their alcoholism (mean, 7.2 years) and the nature of the tasks involved.", "contents": "Intellectual competence of alcoholics. Alcoholic and psychiatric inpatients matched in age and education performed comparably on a battery of cognitive tests. The absence of impairment in the alcoholics is attributed to the relatively short duration of their alcoholism (mean, 7.2 years) and the nature of the tasks involved."}
{"id": "PMID:235681", "title": "Field dependence and self-actualization in alcoholics.", "content": "Field independence and self-actualization were significantly increased in alcoholic patients following a 6-week treatment program. There were no differences, however, between patients treated by drug-assisted individual therapy, individual therapy, or milieu therapy. Some causal factors are hypothesized, and implications for treatment are discussed.", "contents": "Field dependence and self-actualization in alcoholics. Field independence and self-actualization were significantly increased in alcoholic patients following a 6-week treatment program. There were no differences, however, between patients treated by drug-assisted individual therapy, individual therapy, or milieu therapy. Some causal factors are hypothesized, and implications for treatment are discussed."}
{"id": "PMID:235682", "title": "Personality and temperament differences between alcoholics with high and low records of traffic accidents and violations.", "content": "Significant differences on scales of the Guilford-Zimmerman Temperament Survey and the Minnesota Multiphasic Personality Inventory were found between alcoholics with high and low records of traffic accidents and violations.", "contents": "Personality and temperament differences between alcoholics with high and low records of traffic accidents and violations. Significant differences on scales of the Guilford-Zimmerman Temperament Survey and the Minnesota Multiphasic Personality Inventory were found between alcoholics with high and low records of traffic accidents and violations."}
{"id": "PMID:235683", "title": "Spouse response to a self-administered alcoholism screening test.", "content": "A self-administered, expanded version of the Michigan Alcoholism Screening Test was completed by a group of hospitalized alcoholics and by their spouses and counselors, describing the patients. The data obtained from spouse responses was accurate in 90% of the cases; the spouse may be a more reliable source of information about drinking problems than the alcoholic.", "contents": "Spouse response to a self-administered alcoholism screening test. A self-administered, expanded version of the Michigan Alcoholism Screening Test was completed by a group of hospitalized alcoholics and by their spouses and counselors, describing the patients. The data obtained from spouse responses was accurate in 90% of the cases; the spouse may be a more reliable source of information about drinking problems than the alcoholic."}
{"id": "PMID:235684", "title": "The impact of specialized training in alcoholism on management-level professionals.", "content": "Administrative and management-level social workers and nurses significantly increased their alcohol-related work activities during the year after they attended an 8-week alcoholism training program. Measures of attitude change, however, showed no appreciable differences.", "contents": "The impact of specialized training in alcoholism on management-level professionals. Administrative and management-level social workers and nurses significantly increased their alcohol-related work activities during the year after they attended an 8-week alcoholism training program. Measures of attitude change, however, showed no appreciable differences."}
{"id": "PMID:235685", "title": "A descriptive analysis of alcohol education materials.", "content": "Analysis of 832 alcohol education materials (books, pamphlets and leaflets) indicates that the quantity and quality of the materials have increased in recent years. Alcoholism and the effects of alcohol are the major themes for all audience levels. There are few good quality resources for the junior-high and elementary school levels.", "contents": "A descriptive analysis of alcohol education materials. Analysis of 832 alcohol education materials (books, pamphlets and leaflets) indicates that the quantity and quality of the materials have increased in recent years. Alcoholism and the effects of alcohol are the major themes for all audience levels. There are few good quality resources for the junior-high and elementary school levels."}
{"id": "PMID:235686", "title": "Defense mechanisms in men and women alcoholics.", "content": "The responses of men and women alcoholics to the Defense Mechanism Inventory showed that the women scored significantly higher in \"turning against self\" and the men in \"turning against others.\" Although such differences may underlie reported sex differences in the incidence of depression and sociopathic personality disorder, they have also been found in studies of nonalcoholics and psychiatric outpatients.", "contents": "Defense mechanisms in men and women alcoholics. The responses of men and women alcoholics to the Defense Mechanism Inventory showed that the women scored significantly higher in \"turning against self\" and the men in \"turning against others.\" Although such differences may underlie reported sex differences in the incidence of depression and sociopathic personality disorder, they have also been found in studies of nonalcoholics and psychiatric outpatients."}
{"id": "PMID:235688", "title": "A report of a 1972 survey of physician's assistant training programs.", "content": "This article presents select results of a 1972 survey of all physician's assistant training programs in the United States and its territories. The survey gathered a broad range of information useful to federal health manpower policymakers, physician assistant training program administrators, guidance counselors, and prospective students. Responses were received from 75 operational programs and 13 programs still in planning for an estimated response rate of 81 per cent from the estimated 108 programs in existence.", "contents": "A report of a 1972 survey of physician's assistant training programs. This article presents select results of a 1972 survey of all physician's assistant training programs in the United States and its territories. The survey gathered a broad range of information useful to federal health manpower policymakers, physician assistant training program administrators, guidance counselors, and prospective students. Responses were received from 75 operational programs and 13 programs still in planning for an estimated response rate of 81 per cent from the estimated 108 programs in existence."}
{"id": "PMID:235692", "title": "Peanut alkaline lipase.", "content": "Peanut alkaline lipase, (glycerol ester hydrolase EC 3.1.1.3), pH optimum 8.5, was isolated from acetone powders prepared from developing and germinated peanut seed (arachis hypogaea L. var. NC-2). Enzyme activity/seed increased in successive developmental stages. The course of the hydrolytic reaction was linear with regard to enzyme concentration and all times tested up to periods exceeding 60 min. Km for the reaction was determined to be 2.6 times 10-4M. Molecular weight of peanut lipase, as estimated by Sephadex gel filtration and sodium dodecyl sulfate gel electrophoresis, was ca. 55,000.", "contents": "Peanut alkaline lipase. Peanut alkaline lipase, (glycerol ester hydrolase EC 3.1.1.3), pH optimum 8.5, was isolated from acetone powders prepared from developing and germinated peanut seed (arachis hypogaea L. var. NC-2). Enzyme activity/seed increased in successive developmental stages. The course of the hydrolytic reaction was linear with regard to enzyme concentration and all times tested up to periods exceeding 60 min. Km for the reaction was determined to be 2.6 times 10-4M. Molecular weight of peanut lipase, as estimated by Sephadex gel filtration and sodium dodecyl sulfate gel electrophoresis, was ca. 55,000."}
{"id": "PMID:235713", "title": "The clinical pharmacology of hypotensive vasodilator drugs.", "content": "Drugs which lower arterial blood pressure by direct vasodilator action usually have to be combined with beta adrenergic blocking drugs and diuretics for maximum clinical effectiveness. Appreciation of the pharmacodynamic interactions is necessary to individualize drug programmes rationally. Vasodilator drug therapy is remarkable for the lack of side effects such as central nervous system effects, postural hypotension and sexual difficulties which usually characterize most \"antiadrenergic\" drug regiments.", "contents": "The clinical pharmacology of hypotensive vasodilator drugs. Drugs which lower arterial blood pressure by direct vasodilator action usually have to be combined with beta adrenergic blocking drugs and diuretics for maximum clinical effectiveness. Appreciation of the pharmacodynamic interactions is necessary to individualize drug programmes rationally. Vasodilator drug therapy is remarkable for the lack of side effects such as central nervous system effects, postural hypotension and sexual difficulties which usually characterize most \"antiadrenergic\" drug regiments."}
{"id": "PMID:235714", "title": "Vasodilators in the treatment of hypertension.", "content": "Vasodilator drugs play an important role in the treatment of hypertension in 1974. A powerful vasodilator such as diazoxide may be necessary in the control of the most severely affected patients. It should not be forgotten that drugs of the benzothiadiazine group probably act mainly as vasodilators and that their effect is not dependent upon natriuresis and diuresis. New vasodilators such as minoxidil may have an important role in the treatment of hypertension, but these have not yet been adequately assessed in Australia. Both hydrallazine and prazosin produce a significant fall in the blood pressure when added to a combination of a beta blocker and a diuretic, and double-blind studies have shown that the side effects are more predominant with hydrallazine than with prazosin.", "contents": "Vasodilators in the treatment of hypertension. Vasodilator drugs play an important role in the treatment of hypertension in 1974. A powerful vasodilator such as diazoxide may be necessary in the control of the most severely affected patients. It should not be forgotten that drugs of the benzothiadiazine group probably act mainly as vasodilators and that their effect is not dependent upon natriuresis and diuresis. New vasodilators such as minoxidil may have an important role in the treatment of hypertension, but these have not yet been adequately assessed in Australia. Both hydrallazine and prazosin produce a significant fall in the blood pressure when added to a combination of a beta blocker and a diuretic, and double-blind studies have shown that the side effects are more predominant with hydrallazine than with prazosin."}
{"id": "PMID:235735", "title": "The non-enzymic reduction of nitrite by benzyl viologen (free-radical) in the presence and absence of ammonium sulphate.", "content": "Some similarity is inferred between the reaction or reduced benzyl viologen with undissociated nitrous acid, which is significant at pH values below 7 and that with the undissociated product of nitrite ion and ammonium sulphate; presumably ammonium nitrite. This would explain why the presence of ammonium sulphate appreciably offsets the effects of decreasing pH and also the exponential relationship between rate of nitrite loss and ammonium sulphate concentration. There are other features of the reaction which cannot be explained at present, especially with regard to the degree of reduction of benzyl viologen. It is nevertheless apparent that a complex non-enzymic reaction yielding several products occurs when ammonium sulphate is present and that the presence of likely residual quantities after its use in enzyme purification may cause serious errors in enzyme assay.", "contents": "The non-enzymic reduction of nitrite by benzyl viologen (free-radical) in the presence and absence of ammonium sulphate. Some similarity is inferred between the reaction or reduced benzyl viologen with undissociated nitrous acid, which is significant at pH values below 7 and that with the undissociated product of nitrite ion and ammonium sulphate; presumably ammonium nitrite. This would explain why the presence of ammonium sulphate appreciably offsets the effects of decreasing pH and also the exponential relationship between rate of nitrite loss and ammonium sulphate concentration. There are other features of the reaction which cannot be explained at present, especially with regard to the degree of reduction of benzyl viologen. It is nevertheless apparent that a complex non-enzymic reaction yielding several products occurs when ammonium sulphate is present and that the presence of likely residual quantities after its use in enzyme purification may cause serious errors in enzyme assay."}
{"id": "PMID:235736", "title": "On the involvement of a glucose 6-phosphate transport system in the function of microsomal glucose 6-phosphatase.", "content": "A model for microsomal glucose 6-phosphatase (EC 3.1.3.9) is presented. Glucose 6-phosphatase is postulated to be resultant of the coupling of two components of the microsomal membrane: 1) a glucose 6-phosphate - specific transport system which functions to shuttle the sugar phosphate from the cytoplasm to the lumen of the endoplasmic reticulum; and 2) a catalytic component, glucose-6-P phosphohydrolase, bound to the luminal surface of the membrane. A large body of existing data was shown to be consistent with this hypothesis. In particular, the model reconciles well-documented differences in the kinetic properties of the enzyme of untreated and modified microsomal preparations. Characteristic responses of the enzyme to changes in nutritional and hormonal states may be attributed to adaptations which alter the relative capacities of the transport and catalytic components.", "contents": "On the involvement of a glucose 6-phosphate transport system in the function of microsomal glucose 6-phosphatase. A model for microsomal glucose 6-phosphatase (EC 3.1.3.9) is presented. Glucose 6-phosphatase is postulated to be resultant of the coupling of two components of the microsomal membrane: 1) a glucose 6-phosphate - specific transport system which functions to shuttle the sugar phosphate from the cytoplasm to the lumen of the endoplasmic reticulum; and 2) a catalytic component, glucose-6-P phosphohydrolase, bound to the luminal surface of the membrane. A large body of existing data was shown to be consistent with this hypothesis. In particular, the model reconciles well-documented differences in the kinetic properties of the enzyme of untreated and modified microsomal preparations. Characteristic responses of the enzyme to changes in nutritional and hormonal states may be attributed to adaptations which alter the relative capacities of the transport and catalytic components."}
{"id": "PMID:235740", "title": "[\"Drinking the waters\" as a therapeutic exercise in the ionic range].", "content": "While \"drinking the waters\" (198 spa patients), longitudinal section inograms were made - Na, K, Ca, Mg, Cl, P and pH in serum, urine, saliva and perspiration were determined simultaneously and also the acid-base balance conditions in the blood by Astrup's method--and investigated from the point of view of the electrolyte metabolism. Carbonic acid absorbed from the intestine exerts a powerful action, triggering compensatory processes against acidification and leading to an increase in calcium and/or magnesium in the serum. Further, various changes in the ion concentrations, according to the mineral water, can sometimes be traced to an increase in the anion column and sometimes to hormonal effects (suprarenal cortex and medulla). They persist for several weeks after the course of treatment.", "contents": "[\"Drinking the waters\" as a therapeutic exercise in the ionic range]. While \"drinking the waters\" (198 spa patients), longitudinal section inograms were made - Na, K, Ca, Mg, Cl, P and pH in serum, urine, saliva and perspiration were determined simultaneously and also the acid-base balance conditions in the blood by Astrup's method--and investigated from the point of view of the electrolyte metabolism. Carbonic acid absorbed from the intestine exerts a powerful action, triggering compensatory processes against acidification and leading to an increase in calcium and/or magnesium in the serum. Further, various changes in the ion concentrations, according to the mineral water, can sometimes be traced to an increase in the anion column and sometimes to hormonal effects (suprarenal cortex and medulla). They persist for several weeks after the course of treatment."}
{"id": "PMID:235746", "title": "Diuretics, urate excretion and sodium reabsorption: effect of acetazolamide and urinary alkalinization.", "content": "The uricosuric properties of acetazolamide were investigated in order to elucidate the relationship between changes in proximal tubular sodium reabsorption and urate excretion in man. Acetazolamide produced a modest uricosuric response which was not suppressible by pyrazinamide. Alkalinization of the urine with sodium bicarbonate elicited an even smaller increment in the urate clearance. If urinary alkalinization does play a role in the uricosuric response to acetazolamide, it probably decreases urate reabsorption within the distal nephron. The present studies, when taken together with previous work, suggest that alterations in proximal tubular sodium and water reabsorption probably do not play an important role in the normal control of urate excretion or in the pathogenesis of hyperuricemic states. Diuretic-induced hyperuricemia occurring during extracellular fluid volume depletion probably results from either diminished tubular secretion of urate, accelerated postsecretory urate reabsorption, or both.", "contents": "Diuretics, urate excretion and sodium reabsorption: effect of acetazolamide and urinary alkalinization. The uricosuric properties of acetazolamide were investigated in order to elucidate the relationship between changes in proximal tubular sodium reabsorption and urate excretion in man. Acetazolamide produced a modest uricosuric response which was not suppressible by pyrazinamide. Alkalinization of the urine with sodium bicarbonate elicited an even smaller increment in the urate clearance. If urinary alkalinization does play a role in the uricosuric response to acetazolamide, it probably decreases urate reabsorption within the distal nephron. The present studies, when taken together with previous work, suggest that alterations in proximal tubular sodium and water reabsorption probably do not play an important role in the normal control of urate excretion or in the pathogenesis of hyperuricemic states. Diuretic-induced hyperuricemia occurring during extracellular fluid volume depletion probably results from either diminished tubular secretion of urate, accelerated postsecretory urate reabsorption, or both."}
{"id": "PMID:235747", "title": "Hyperuricemic nephropathy: pathologic features and factors influencing urate deposition.", "content": "The three general types of renal pathology associated with hyperuricemia are reviewed. Factors influencing urate solubility are discussed, as well as the effect of uricosuric drugs on renal urate handling, with particular emphasis upon their efficacy in competing with urate for protein binding sites. In addition, a new experimental model of hyperuricemic nephropathy is described which could yield valuable data concerning the complex relationships between hyperuricemia, urate deposition and renal function.", "contents": "Hyperuricemic nephropathy: pathologic features and factors influencing urate deposition. The three general types of renal pathology associated with hyperuricemia are reviewed. Factors influencing urate solubility are discussed, as well as the effect of uricosuric drugs on renal urate handling, with particular emphasis upon their efficacy in competing with urate for protein binding sites. In addition, a new experimental model of hyperuricemic nephropathy is described which could yield valuable data concerning the complex relationships between hyperuricemia, urate deposition and renal function."}
{"id": "PMID:235749", "title": "Central nervous system findings in the newborn monkey following severe in utero partial asphyxia.", "content": "Seizures, brain swelling, and cortical necrosis have been observed in the newborn rhesus monkey following a 2 to 4-hour period of intrauterine partial asphyxia produced by halothane-induced maternal hypotension. These clinical and neuropathologic findings are similar to those seen in human newborn infants who have experienced an episode of intrauterine asphyxia from such a cause as premature placental separation. The present study strongly indicates that fetal partial asphyxia, from any cause, in the absence of fetal circulatory collapse or fetal head compression, may be the primary event that sets in motion a vicious cycle of brain swelling and impaired cerebral blood flow, leading finally to cerebral necrosis.", "contents": "Central nervous system findings in the newborn monkey following severe in utero partial asphyxia. Seizures, brain swelling, and cortical necrosis have been observed in the newborn rhesus monkey following a 2 to 4-hour period of intrauterine partial asphyxia produced by halothane-induced maternal hypotension. These clinical and neuropathologic findings are similar to those seen in human newborn infants who have experienced an episode of intrauterine asphyxia from such a cause as premature placental separation. The present study strongly indicates that fetal partial asphyxia, from any cause, in the absence of fetal circulatory collapse or fetal head compression, may be the primary event that sets in motion a vicious cycle of brain swelling and impaired cerebral blood flow, leading finally to cerebral necrosis."}
{"id": "PMID:235748", "title": "[Crocodile tears syndrome].", "content": "Among 245 patients with peripheral facial nerve paralysis in 16 cases gustatory lacrimation was observed to remain as a sequel of paralysis. On the basis of clinical observation, testing of nerve excitability, Schirmer's test, examination of taste and laryngological examinations it was found that gustatory lacrimation occurs only in patients with complete and incomplete degeneration of the nerve situated most frequently at the ganglion geniculi or in the suprageniculate region. Already in the first stage of paralysis when degeneration of the nerve is found with lack or very marked reduction of lacrimation on the involved side it may be predicted with a high probability that crocodile tears will appear. In treatment of this phenomenon antihistamine and anticholinergic agents may be tried with good effects. In severe cases surgical intervention may be considered with elimination of the pathological reflex by sectioning the chorda tympani or Jaeobsen's nerve depending on the pathway of the reflex.", "contents": "[Crocodile tears syndrome]. Among 245 patients with peripheral facial nerve paralysis in 16 cases gustatory lacrimation was observed to remain as a sequel of paralysis. On the basis of clinical observation, testing of nerve excitability, Schirmer's test, examination of taste and laryngological examinations it was found that gustatory lacrimation occurs only in patients with complete and incomplete degeneration of the nerve situated most frequently at the ganglion geniculi or in the suprageniculate region. Already in the first stage of paralysis when degeneration of the nerve is found with lack or very marked reduction of lacrimation on the involved side it may be predicted with a high probability that crocodile tears will appear. In treatment of this phenomenon antihistamine and anticholinergic agents may be tried with good effects. In severe cases surgical intervention may be considered with elimination of the pathological reflex by sectioning the chorda tympani or Jaeobsen's nerve depending on the pathway of the reflex."}
{"id": "PMID:235753", "title": "Metabolic studies of a family with massive formiminoglutamic aciduria.", "content": "We have described two siblings who excrete massive amounts (up to 3.89 mmol/24 hr) of N-formiminoglutamic acid (FIGLU) in their urine. This unusual compound was isolated from urine, purified, and firmly identified as FIGLU by combined gas chromatography-mass spectrometry. The patients presumably have a deficiency in activity of the hepatic enzyme, glutamate formiminotransferase, which carries out the fourth sequential step in the main pathway of histidine degradation. Unlike children reported previously with this disorder, our patients had normal serum folate levels, had no hematologic abnormalities, and were not mentally retarded. Very small amounts of FIGLU were present in the plasma of one of the patients, but FIGLU was not detectable in the cerebrospinal fluid of either patient. Administration of pharmacologic doses of folic or folinic acid produced a decrease in excretion of FIGLU in urine. Histidine loading caused a small and comparable urinary excretion of FIGLU in the children's parents and in control adult subjects.", "contents": "Metabolic studies of a family with massive formiminoglutamic aciduria. We have described two siblings who excrete massive amounts (up to 3.89 mmol/24 hr) of N-formiminoglutamic acid (FIGLU) in their urine. This unusual compound was isolated from urine, purified, and firmly identified as FIGLU by combined gas chromatography-mass spectrometry. The patients presumably have a deficiency in activity of the hepatic enzyme, glutamate formiminotransferase, which carries out the fourth sequential step in the main pathway of histidine degradation. Unlike children reported previously with this disorder, our patients had normal serum folate levels, had no hematologic abnormalities, and were not mentally retarded. Very small amounts of FIGLU were present in the plasma of one of the patients, but FIGLU was not detectable in the cerebrospinal fluid of either patient. Administration of pharmacologic doses of folic or folinic acid produced a decrease in excretion of FIGLU in urine. Histidine loading caused a small and comparable urinary excretion of FIGLU in the children's parents and in control adult subjects."}
{"id": "PMID:235756", "title": "Symposium. ENT for nonspecialists. Serous otitis media.", "content": "Serous otitis media is a capricious entity that can cause conductive deafness. The condition is most common in children, who often cannot describe the attending symptoms of deafness, fullness, and pressure. The basic contributing factor is inadequate function of the eustachian tube. Function improves as the child approaches 12 years of age. Underlying factors such as infections, adenoidal hypertrophy, and allergic states also must be managed. The otitis media may be treated medically or surgically.", "contents": "Symposium. ENT for nonspecialists. Serous otitis media. Serous otitis media is a capricious entity that can cause conductive deafness. The condition is most common in children, who often cannot describe the attending symptoms of deafness, fullness, and pressure. The basic contributing factor is inadequate function of the eustachian tube. Function improves as the child approaches 12 years of age. Underlying factors such as infections, adenoidal hypertrophy, and allergic states also must be managed. The otitis media may be treated medically or surgically."}
{"id": "PMID:235757", "title": "Symposium. ENT for nonspecialists. External otitis.", "content": "Simple treatment usually suffices for the control of acute external otitis, This consists of meticulous cleaning of the ear canal and application of antibiotic-corticosteroid drops. Good local care of the ear can prevent both the chronic and the acute forms of external otitis. Malignant external otitis is an uncommon but lethal type that most often accompanies diabetes. If this condition is diagnosed, hospitalization and aggressive treatment are then a necessity.", "contents": "Symposium. ENT for nonspecialists. External otitis. Simple treatment usually suffices for the control of acute external otitis, This consists of meticulous cleaning of the ear canal and application of antibiotic-corticosteroid drops. Good local care of the ear can prevent both the chronic and the acute forms of external otitis. Malignant external otitis is an uncommon but lethal type that most often accompanies diabetes. If this condition is diagnosed, hospitalization and aggressive treatment are then a necessity."}
{"id": "PMID:235758", "title": "13-C nuclear magnetic resonance studies on the mechanism of action of carbonic anhydrase.", "content": "Binding of the substrate, bicarbonate, to bovine cobalt carbonic anhydrase (carbonate hydrolyase, EC 4.2.1.1) has been studied with 13-C nuclear magnetic resonance. Two binding sites for bicarbonate have been identified. One loosely binds bicarbonate, inhibits p-nitrophenyl acetate activity, and must be the bicarbonate substrate binding site; the other tightly binds bicarbonate, is noninhibitory, and plays another role. Spinlattice relaxation times for the carbon atom of bicarbonate indicate that the substrate bicarbonate is bound directly to the metal center of the enzyme, while the other bicarbonate is bound in the outer coordination sphere of the metal. It is proposed that dehydration proceeds via HCO-3 minus coordinated directly to the metal center, while the outer sphere bicarbonate facilitates catalytically important proton transfers.", "contents": "13-C nuclear magnetic resonance studies on the mechanism of action of carbonic anhydrase. Binding of the substrate, bicarbonate, to bovine cobalt carbonic anhydrase (carbonate hydrolyase, EC 4.2.1.1) has been studied with 13-C nuclear magnetic resonance. Two binding sites for bicarbonate have been identified. One loosely binds bicarbonate, inhibits p-nitrophenyl acetate activity, and must be the bicarbonate substrate binding site; the other tightly binds bicarbonate, is noninhibitory, and plays another role. Spinlattice relaxation times for the carbon atom of bicarbonate indicate that the substrate bicarbonate is bound directly to the metal center of the enzyme, while the other bicarbonate is bound in the outer coordination sphere of the metal. It is proposed that dehydration proceeds via HCO-3 minus coordinated directly to the metal center, while the outer sphere bicarbonate facilitates catalytically important proton transfers."}
{"id": "PMID:235759", "title": "Nerve growth factor induces volume increase and enhances tyrosine hydroxylase synthesis in chemically axotomized sympathetic ganglia of newborn rats.", "content": "Concomitant daily treatment of newborn rats for a 2-week to 1-month period with 10 mug/g of body weight of nerve growth factor and 100 mug/g of body weight of 6-hydroxydopamine produces in the cell bodies of adrenergic neurons the characteristic effects of the growth factor but in the nerve terminals the characteristic effects of 6-hydroxydopamine. The dual opposite effects result in a striking volume increase of sympathetic ganglia which far exceeds that produced by nerve growth factor alone. The selective induction of tyrosine hydroxylase [L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] in these chemically axotomized adrenergic neurons is even more pronounced than that produced by nerve growth factor alone in intact neurons.", "contents": "Nerve growth factor induces volume increase and enhances tyrosine hydroxylase synthesis in chemically axotomized sympathetic ganglia of newborn rats. Concomitant daily treatment of newborn rats for a 2-week to 1-month period with 10 mug/g of body weight of nerve growth factor and 100 mug/g of body weight of 6-hydroxydopamine produces in the cell bodies of adrenergic neurons the characteristic effects of the growth factor but in the nerve terminals the characteristic effects of 6-hydroxydopamine. The dual opposite effects result in a striking volume increase of sympathetic ganglia which far exceeds that produced by nerve growth factor alone. The selective induction of tyrosine hydroxylase [L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] in these chemically axotomized adrenergic neurons is even more pronounced than that produced by nerve growth factor alone in intact neurons."}
{"id": "PMID:235760", "title": "Ultrastructural localization of tyrosine hydroxylase in noradrenergic neurons of brain.", "content": "Tyrosine hydroxylase (EC 1.14.16.2), the enzyme catalyzing the rate-limiting step in catecholamine biosynthesis, was localized by electron microscopy within noradrenergic neurons of the nucleus locus coeruleus of the rat brain with a specific antibody to tyrosine hydroxylase labeled by the peroxidase-antiperoxidase immunohistochemical method. Labeled cell bodies and their processes were easily distinguished from unstained neuronal elements in the neuropil. The hydroxylase was only seen in the neuronal cytoplasm. Its distribution in processes was different from that in cell soma. In longitudinal sections of axons and dendrites, the peroxides reaction product appeared as fiber-like strands aligned parallel with the plasma membrane. In cross section, the labeled structures had a diameter of 220 A and exhibited an orderly distribution within the processes. The size and distribution of the peroxidase-stained structures suggest that they are neurotubules. In the perikarya, the cytoplasm was diffusely stained; the reaction was most intense on membranes of endoplasmic reticulum and Golgi apparatus, whereas lysosomes and mitochondria did not stain. The ultrastructural localization of tyrosine hydroxylase is consistent with biochemical data suggesting that the enzyme exists in different states in cell body and processes. The ultrastructural identification of enzymes subserving synthesis of neurotransmitters in central neurons and their processes may provide a useful tool in mapping the distribution of chemically specific synapses on identifiable neurons in brain.", "contents": "Ultrastructural localization of tyrosine hydroxylase in noradrenergic neurons of brain. Tyrosine hydroxylase (EC 1.14.16.2), the enzyme catalyzing the rate-limiting step in catecholamine biosynthesis, was localized by electron microscopy within noradrenergic neurons of the nucleus locus coeruleus of the rat brain with a specific antibody to tyrosine hydroxylase labeled by the peroxidase-antiperoxidase immunohistochemical method. Labeled cell bodies and their processes were easily distinguished from unstained neuronal elements in the neuropil. The hydroxylase was only seen in the neuronal cytoplasm. Its distribution in processes was different from that in cell soma. In longitudinal sections of axons and dendrites, the peroxides reaction product appeared as fiber-like strands aligned parallel with the plasma membrane. In cross section, the labeled structures had a diameter of 220 A and exhibited an orderly distribution within the processes. The size and distribution of the peroxidase-stained structures suggest that they are neurotubules. In the perikarya, the cytoplasm was diffusely stained; the reaction was most intense on membranes of endoplasmic reticulum and Golgi apparatus, whereas lysosomes and mitochondria did not stain. The ultrastructural localization of tyrosine hydroxylase is consistent with biochemical data suggesting that the enzyme exists in different states in cell body and processes. The ultrastructural identification of enzymes subserving synthesis of neurotransmitters in central neurons and their processes may provide a useful tool in mapping the distribution of chemically specific synapses on identifiable neurons in brain."}
{"id": "PMID:235761", "title": "Life history of Coelomomyces psorophorae.", "content": "The mosquito parasite, Coelomomyces psorophorae (Blastocladiales, Chytridiomycetes) alternates obligately between the larvae of Culiseta inornata and the copepod Cyclops vernalis. Isogametes, derived from heterothallic, wall-less gametangia which develop in the copepod, fuse to produce a diploid zygote that subsequently infects the mosquito host. Zoospores from the resistant sporangia which are produced in the haemocoel of the mosquito infect the copepod. A tentative life-history is proposed and implications of these discoveries for the biology, taxonomy, and possible role of Coelomomyces in biological control are discussed.", "contents": "Life history of Coelomomyces psorophorae. The mosquito parasite, Coelomomyces psorophorae (Blastocladiales, Chytridiomycetes) alternates obligately between the larvae of Culiseta inornata and the copepod Cyclops vernalis. Isogametes, derived from heterothallic, wall-less gametangia which develop in the copepod, fuse to produce a diploid zygote that subsequently infects the mosquito host. Zoospores from the resistant sporangia which are produced in the haemocoel of the mosquito infect the copepod. A tentative life-history is proposed and implications of these discoveries for the biology, taxonomy, and possible role of Coelomomyces in biological control are discussed."}
{"id": "PMID:235762", "title": "Role of amino groups in formation of human lymphocyte-xenogeneic erythrocyte rosettes; a proposed mechanism for antigen recognition.", "content": "Formation of coulombic and possible hydrogen bonds between amino groups on human lymphocytes and negatively charged sites on sheep erythrocytes is involved in rosette formation. Supportive evidence includes rosette inhibition by chemical binding of lymphocyte membrane amino groups, and the results of changing the pH, ionic concentration, and temperature of the reaction. Although the possibility has not been excluded that the amino group dependence of this reaction is related to the property of certain proteins attached to the T-cell (thymus processed) surface, it is suggested that this dependence may be related to a charge pattern recognition in the form of \"codes\" present on the T-cell membrane. It is speculated that this type of recognition may be a contributory mechanism in the initiation of the T-cell-dependent immune response.", "contents": "Role of amino groups in formation of human lymphocyte-xenogeneic erythrocyte rosettes; a proposed mechanism for antigen recognition. Formation of coulombic and possible hydrogen bonds between amino groups on human lymphocytes and negatively charged sites on sheep erythrocytes is involved in rosette formation. Supportive evidence includes rosette inhibition by chemical binding of lymphocyte membrane amino groups, and the results of changing the pH, ionic concentration, and temperature of the reaction. Although the possibility has not been excluded that the amino group dependence of this reaction is related to the property of certain proteins attached to the T-cell (thymus processed) surface, it is suggested that this dependence may be related to a charge pattern recognition in the form of \"codes\" present on the T-cell membrane. It is speculated that this type of recognition may be a contributory mechanism in the initiation of the T-cell-dependent immune response."}
{"id": "PMID:235763", "title": "Lipoprotein lipase of ovarian follicles in the domestic chicken (Gallus domesticus) (38537).", "content": "A lipase, bearing the characteristics of adipose tissue lipoprotein lipase (LPL) has been characterized in avian ovarian granulosa cells. The activity is low in cells from follicles weighing less than 0.5 g; in heavier follicles which have entered the rapid growth phase, significant activity (1 mumole fatty acid/mg protein/hr) could be identified. Granulosa LPL provides follicular tissues with the requisite enzyme system to hydrolyze very low density lipoprotein triglyceride en route to the oocyte.", "contents": "Lipoprotein lipase of ovarian follicles in the domestic chicken (Gallus domesticus) (38537). A lipase, bearing the characteristics of adipose tissue lipoprotein lipase (LPL) has been characterized in avian ovarian granulosa cells. The activity is low in cells from follicles weighing less than 0.5 g; in heavier follicles which have entered the rapid growth phase, significant activity (1 mumole fatty acid/mg protein/hr) could be identified. Granulosa LPL provides follicular tissues with the requisite enzyme system to hydrolyze very low density lipoprotein triglyceride en route to the oocyte."}
{"id": "PMID:235764", "title": "Isolation and some characteristics of glutathione reductase from rabbit erythrocytes (38548).", "content": "Glutathione reductase from rabbit erythrocytes was pruified to homogeneity and found to be a monomer with a mol wt of 60,000. Both NADPH and HADH were capable of acting as cofactors for the reduction of GSSG and the following kinetic values were obtained: Km, GSSG = 120 muM; Km, NADPH = 37 muM; Vmax = 23 mumoles NADPH/min/mg protein, Km, NADH = 420 muM; Vmax = 3 mumoles NADH/min/mg protein. Rabbit erythrocyte GR exhibited substrate inhibition, and was susceptible to inhibition by p-hydroxymercuribenzoate under certain conditions.", "contents": "Isolation and some characteristics of glutathione reductase from rabbit erythrocytes (38548). Glutathione reductase from rabbit erythrocytes was pruified to homogeneity and found to be a monomer with a mol wt of 60,000. Both NADPH and HADH were capable of acting as cofactors for the reduction of GSSG and the following kinetic values were obtained: Km, GSSG = 120 muM; Km, NADPH = 37 muM; Vmax = 23 mumoles NADPH/min/mg protein, Km, NADH = 420 muM; Vmax = 3 mumoles NADH/min/mg protein. Rabbit erythrocyte GR exhibited substrate inhibition, and was susceptible to inhibition by p-hydroxymercuribenzoate under certain conditions."}
{"id": "PMID:235765", "title": "Mechanisms of oral staphylococcal enterotoxin B-induced emesis in the monkey (38553).", "content": "Vomition is the most consistent response to oral SEB challenge in the monkey.  The technique of cross-circulation clearly differentiates local neural phenomenon from humoral mechanisms.  Our results support the theory that SED-induced vomition follows stimulation of local neural receptors in the gut.  The evidence indicates no significant amount of enterotoxin absorption or stimulation of vomition by any centrally acting humoral mechanism.", "contents": "Mechanisms of oral staphylococcal enterotoxin B-induced emesis in the monkey (38553). Vomition is the most consistent response to oral SEB challenge in the monkey.  The technique of cross-circulation clearly differentiates local neural phenomenon from humoral mechanisms.  Our results support the theory that SED-induced vomition follows stimulation of local neural receptors in the gut.  The evidence indicates no significant amount of enterotoxin absorption or stimulation of vomition by any centrally acting humoral mechanism."}
{"id": "PMID:235766", "title": "Effect of water and mouthwashes on pH of oral monkey mucosa.", "content": "Among the many factors involved in homeostasis, maintenance of hydrogen-ion concentration is one of the most important functions of the body. Surface pH measurements of oral tissues after rinsing with water or mouthwashes are meager. This report presents results of the effect of tap water and 9 commercial mouthwashes on intraoral pH under controlled conditions. Nine rhesus monkeys, 5 females and 4 males between 3 and 8 years of age, were used in this study. During measurements they were sedated with phencyclidine hydrochloride and anesthetized with pentobarbital sodium. A Beckman pH meter with potassium chloride and silver chloride combination electrode was utilized. The pH was measured on the lingual gingva opposite the right lower first molar. Control readings were obtained, then a 30-sec pulsed-water-jet lavage with tap water with a force of 5 psi was given, and the pH was observed for 5 min. The 1 ml of mouthwash was administered on a thoroughly soaked gauze for 30 sec. This procedure was repeated 3 times on different days for each of the 9 mouthwashes used. All of the measurements showed a decrease in pH after tap-water lavage. In general, acid mouthwashes decreased the pH, while mouthwashes with alkaline pH's increased the pH of the oral tissues. The effects on pH was, however, transitory since the major change appeared within 8 min and approached equilibrium by 12 to 16 min.", "contents": "Effect of water and mouthwashes on pH of oral monkey mucosa. Among the many factors involved in homeostasis, maintenance of hydrogen-ion concentration is one of the most important functions of the body. Surface pH measurements of oral tissues after rinsing with water or mouthwashes are meager. This report presents results of the effect of tap water and 9 commercial mouthwashes on intraoral pH under controlled conditions. Nine rhesus monkeys, 5 females and 4 males between 3 and 8 years of age, were used in this study. During measurements they were sedated with phencyclidine hydrochloride and anesthetized with pentobarbital sodium. A Beckman pH meter with potassium chloride and silver chloride combination electrode was utilized. The pH was measured on the lingual gingva opposite the right lower first molar. Control readings were obtained, then a 30-sec pulsed-water-jet lavage with tap water with a force of 5 psi was given, and the pH was observed for 5 min. The 1 ml of mouthwash was administered on a thoroughly soaked gauze for 30 sec. This procedure was repeated 3 times on different days for each of the 9 mouthwashes used. All of the measurements showed a decrease in pH after tap-water lavage. In general, acid mouthwashes decreased the pH, while mouthwashes with alkaline pH's increased the pH of the oral tissues. The effects on pH was, however, transitory since the major change appeared within 8 min and approached equilibrium by 12 to 16 min."}
{"id": "PMID:235767", "title": "Effects of clozapine, thioridazine, perlapine and haloperidol on the metabolism of the biogenic amines in the brain of the rat.", "content": "The effects of clozapine, thioridazine, perlapine and haloperidol on the metabolism of the biogenic amines in the brain of the rat have been investigated. Haloperidol, perlapine and thioridazine induce catalepsy and enhance the turnover of DA in the striatum as indicated by the dose-dependent increase in the DA-metabolites, HVA and DOPAC. These effects are due to blockade of dopaminergic transmission, haloperidol being far more potent than perlapine or thiridazine. Clozapine differs from these agents in that it elevates the concentration of striatal DA. The increase of the concentrations of HVA and DOPAC by clozapine is not accompanied by development of catalepsy. Therefore, clozapine seems to influence striatal DA by a mechanism other than DA-receptor blockade. All four drugs enhance the turnover of NA in the brain stem. This effect is probably secondary to the blockade of NA-receptors. There was no correlation between the effects on NA-metabolism and the EEG-arousal inhibitory activities of these agents or their clinical antipsychotic effects. Clozapine increase the concentration of 5-HT and 5-HIAA in the brain. This effect was not seen with the other drugs. Perlapine seems to enhance the turnover of 5-HT, whereas haloperidol reduced the 5-HT concentration. Thioridazine appears to have no effect on the metabolism of 5-HT.", "contents": "Effects of clozapine, thioridazine, perlapine and haloperidol on the metabolism of the biogenic amines in the brain of the rat. The effects of clozapine, thioridazine, perlapine and haloperidol on the metabolism of the biogenic amines in the brain of the rat have been investigated. Haloperidol, perlapine and thioridazine induce catalepsy and enhance the turnover of DA in the striatum as indicated by the dose-dependent increase in the DA-metabolites, HVA and DOPAC. These effects are due to blockade of dopaminergic transmission, haloperidol being far more potent than perlapine or thiridazine. Clozapine differs from these agents in that it elevates the concentration of striatal DA. The increase of the concentrations of HVA and DOPAC by clozapine is not accompanied by development of catalepsy. Therefore, clozapine seems to influence striatal DA by a mechanism other than DA-receptor blockade. All four drugs enhance the turnover of NA in the brain stem. This effect is probably secondary to the blockade of NA-receptors. There was no correlation between the effects on NA-metabolism and the EEG-arousal inhibitory activities of these agents or their clinical antipsychotic effects. Clozapine increase the concentration of 5-HT and 5-HIAA in the brain. This effect was not seen with the other drugs. Perlapine seems to enhance the turnover of 5-HT, whereas haloperidol reduced the 5-HT concentration. Thioridazine appears to have no effect on the metabolism of 5-HT."}
{"id": "PMID:235776", "title": "Effects of iproveratril on isolated heart mitochondria.", "content": "The effects of iproveratril on oxygen uptake and oxidative phosphorylation of succinate, glutamate and alfa-ketoglutarate were studied. Oxidative phosphorylation and oxidation of NAD+-linked substrated by heart mitochondria were depressed by 1.15 times 10-3M iproveratril. The activity of NADH-oxidase, NADH-cytochrome c reductase and heart mitochondrial transporting particles were depressed by iproveratril. When succinate was the substrate oxidative phosphorylation was depressed but oxygen uptake was stimulated about 370%. Swelling induced by iproveratril was analysed by electron microscopy.", "contents": "Effects of iproveratril on isolated heart mitochondria. The effects of iproveratril on oxygen uptake and oxidative phosphorylation of succinate, glutamate and alfa-ketoglutarate were studied. Oxidative phosphorylation and oxidation of NAD+-linked substrated by heart mitochondria were depressed by 1.15 times 10-3M iproveratril. The activity of NADH-oxidase, NADH-cytochrome c reductase and heart mitochondrial transporting particles were depressed by iproveratril. When succinate was the substrate oxidative phosphorylation was depressed but oxygen uptake was stimulated about 370%. Swelling induced by iproveratril was analysed by electron microscopy."}
{"id": "PMID:235777", "title": "Coenzyme specificity in the glycolysis of intraocular fluids.", "content": "Toward elucidation of the glycolysis in the vitreous and aqueous of several animal species, coenzymes of this scheme, NAD, NADH and ATP were assayed but found to be virtually absent. To further assess this pathway, ADP and NADPH in addition to the above were introduced singly and in combination with 0.20 ml-aliquots of the guinea pig aqueous and vitreous under anaerobic conditions and the absorbance followed spectrophotometrically at 340 nm. Only NADH produced an immediate observable response and the rate of change was greater for the virteous. The action of oxamate and iodacetate was also screened. The experiments point to the LDH-catalyzed step as responsible for the observed effect.", "contents": "Coenzyme specificity in the glycolysis of intraocular fluids. Toward elucidation of the glycolysis in the vitreous and aqueous of several animal species, coenzymes of this scheme, NAD, NADH and ATP were assayed but found to be virtually absent. To further assess this pathway, ADP and NADPH in addition to the above were introduced singly and in combination with 0.20 ml-aliquots of the guinea pig aqueous and vitreous under anaerobic conditions and the absorbance followed spectrophotometrically at 340 nm. Only NADH produced an immediate observable response and the rate of change was greater for the virteous. The action of oxamate and iodacetate was also screened. The experiments point to the LDH-catalyzed step as responsible for the observed effect."}
{"id": "PMID:235778", "title": "Evidence for a small functional pool of serotonin in neurohumoral transmission.", "content": "\"Scottie Cramp\" is a genetic neurologic disease which occurs in the Scottish terrier  breed of dogs. Decreasing central nervous system (CNS) concentrations of serotonin (5-HT) via para-chlorophenylalanine (pCPA) will profoundly increase the severity of the disease although the basic defect does not involve serotonergic neurons. The purpose of this study was to attempt to correlate the effect of p-CPA on the clinical signs of the disease with the alteration in serotonin synthesis and concentration in the CNS. Synthesis was estimated by following the rise in cisternal cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) concentrations with time following probenecid injection. Concentration of serotonin in the CNS was estimated by measuring cisternal CSF 5-HIAA concentrations. The results suggest that serotonin may be synthesized in excess of neuronal transmitter needs and that the estimation of whole brain turnover rates and concentrations of 5-HT may not yield a true measure of serotonergic neuronal activity.", "contents": "Evidence for a small functional pool of serotonin in neurohumoral transmission. \"Scottie Cramp\" is a genetic neurologic disease which occurs in the Scottish terrier  breed of dogs. Decreasing central nervous system (CNS) concentrations of serotonin (5-HT) via para-chlorophenylalanine (pCPA) will profoundly increase the severity of the disease although the basic defect does not involve serotonergic neurons. The purpose of this study was to attempt to correlate the effect of p-CPA on the clinical signs of the disease with the alteration in serotonin synthesis and concentration in the CNS. Synthesis was estimated by following the rise in cisternal cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) concentrations with time following probenecid injection. Concentration of serotonin in the CNS was estimated by measuring cisternal CSF 5-HIAA concentrations. The results suggest that serotonin may be synthesized in excess of neuronal transmitter needs and that the estimation of whole brain turnover rates and concentrations of 5-HT may not yield a true measure of serotonergic neuronal activity."}
{"id": "PMID:235779", "title": "Myocardial function during hypoxia: protective effect of dimethyl sulfoxide (DMSO).", "content": "Electrically driven rabbit left atria were exposed to 20 min periods of hypoxia in the presence and absence of dimethyl sulfoxide (DMSO) or sucrose. Contractile strength declined significantly less than control when tissues were exposed to DMSO during hypoxia. On reoxygenation tissues treated with DMSO recovered pre-hypoxia contractile strength more slowly. Sucrose did not protect tissues during hypoxia. Comparison of results with DMSO and sucrose indicated that tissue depression prior to hypoxia could not explain the action of DMSO. Kinetic analysis performed on tension decline which occurred during hypoxia showed that two components were involved; rate of tension loss in both components was decreased by DMSO and there was a shift in the percentage of decline to the slower component. These data indicate that DMSO may increase energy availability, increase efficiency of energy utilization, or possibly affect the shift from aerobic to anaerobic metabolism during hypoxia, but not during the post-hypoxic recovery period.", "contents": "Myocardial function during hypoxia: protective effect of dimethyl sulfoxide (DMSO). Electrically driven rabbit left atria were exposed to 20 min periods of hypoxia in the presence and absence of dimethyl sulfoxide (DMSO) or sucrose. Contractile strength declined significantly less than control when tissues were exposed to DMSO during hypoxia. On reoxygenation tissues treated with DMSO recovered pre-hypoxia contractile strength more slowly. Sucrose did not protect tissues during hypoxia. Comparison of results with DMSO and sucrose indicated that tissue depression prior to hypoxia could not explain the action of DMSO. Kinetic analysis performed on tension decline which occurred during hypoxia showed that two components were involved; rate of tension loss in both components was decreased by DMSO and there was a shift in the percentage of decline to the slower component. These data indicate that DMSO may increase energy availability, increase efficiency of energy utilization, or possibly affect the shift from aerobic to anaerobic metabolism during hypoxia, but not during the post-hypoxic recovery period."}
{"id": "PMID:235782", "title": "Effect of gastric surgery on the gastrointestinal drug absorption in man.", "content": "The effect of gastric surgery on the absorption of quinidine, ethambutol, and sulphafurazole was studied in 14 male patients, all serving as their own controls. Antrectomy with gastroduodenostomy (ABI) and selective vagotomy lowered the serum levels of all drugs significantly during the 6-hour test period. Excretion of drugs in 6-hour urine also decreased. Three patients showed practically no absorption up to 2 hours, and even therafter the absorption was lowered. Over one year after operation the urinary excretion of ethambutol, but not of the other drugs, was improved. ABI alone did not modify absorption. Preoperative gastric retention seemed to delay absorption.", "contents": "Effect of gastric surgery on the gastrointestinal drug absorption in man. The effect of gastric surgery on the absorption of quinidine, ethambutol, and sulphafurazole was studied in 14 male patients, all serving as their own controls. Antrectomy with gastroduodenostomy (ABI) and selective vagotomy lowered the serum levels of all drugs significantly during the 6-hour test period. Excretion of drugs in 6-hour urine also decreased. Three patients showed practically no absorption up to 2 hours, and even therafter the absorption was lowered. Over one year after operation the urinary excretion of ethambutol, but not of the other drugs, was improved. ABI alone did not modify absorption. Preoperative gastric retention seemed to delay absorption."}
{"id": "PMID:235783", "title": "The effect of duodenal juice on the intrinsic factor (IF) activity in gastric juice.", "content": "Duodenal juice, collected during basal conditions and during stimulation by pentagastrin, secretin, or cholecystokinin, was incubated with neutralized normal gastric juice. High concentrations of bile or proteolytic activity were accompanied by decrease of IF concentration. The inhibition was time- and temperature-dependent, increased significantly at low pH values, and seemed to be partly due to competitive inhibition by unspecific vitamin B12-binding activity. The results are of importance for measurements of IF concentration in gastric juice.", "contents": "The effect of duodenal juice on the intrinsic factor (IF) activity in gastric juice. Duodenal juice, collected during basal conditions and during stimulation by pentagastrin, secretin, or cholecystokinin, was incubated with neutralized normal gastric juice. High concentrations of bile or proteolytic activity were accompanied by decrease of IF concentration. The inhibition was time- and temperature-dependent, increased significantly at low pH values, and seemed to be partly due to competitive inhibition by unspecific vitamin B12-binding activity. The results are of importance for measurements of IF concentration in gastric juice."}
{"id": "PMID:235784", "title": "The effect of carbachol and pentagastrin on the gastric secretion of acid pepsin, and intrinsic factor (IF) in man.", "content": "Intravenous infusions of carbachol and pentagastrin were given separately or simultaneously in 6 healthy students. The volume of gastric secretion and the concentration and output of acid, pepsin, and IF increased significantly during infusion of carbachol alone, whereas the plasma gastrin concentration remained unchanged. Carbachol had no effect on the acid, pepsin, and IF secretion by pentagastrin. The results indicate an effect of carbachol on acid, pepsin, and IF secretion, independent of changes in plasma gastrin concentration. No synergistic or potentiating effect was demonstrated between carbachol and pentagastrin.", "contents": "The effect of carbachol and pentagastrin on the gastric secretion of acid pepsin, and intrinsic factor (IF) in man. Intravenous infusions of carbachol and pentagastrin were given separately or simultaneously in 6 healthy students. The volume of gastric secretion and the concentration and output of acid, pepsin, and IF increased significantly during infusion of carbachol alone, whereas the plasma gastrin concentration remained unchanged. Carbachol had no effect on the acid, pepsin, and IF secretion by pentagastrin. The results indicate an effect of carbachol on acid, pepsin, and IF secretion, independent of changes in plasma gastrin concentration. No synergistic or potentiating effect was demonstrated between carbachol and pentagastrin."}
{"id": "PMID:235785", "title": "The effect of atropine and vagotomy on the secretion of gastric intrinsic factor (IF) in man.", "content": "The gastric secretion of IF, acid, and pepsin during basal conditions and stimulation by pentagastrin decreased significantly in 8 unoperated duodenal ulcer patients following administration of atropine. The basal concentrations of acid and pepsin decreased, whereas that of IF remained unchanged. An increase of plasma gastrin concentration from the basal value was observed after injection of atropine alone. The secretions of IF and acid decreased significantly from the pre-operative values after proximal gastric vagotomy in 7 duodenal ulcer patients. The basal IF output decreased by 19.8 per cent and the stimulated output by 41.4 per cent. The basal and stimulated secretions of acid decreased by 50.0 and 44.1 per cent, respectively. It is suggested that the smaller reduction of IF than of acid may be of importance for the vitamin B12 absorption after vagotomy. The decreased secretion of IF was secondary to the reduction of volume both after'medical' and surgical vagotomy.", "contents": "The effect of atropine and vagotomy on the secretion of gastric intrinsic factor (IF) in man. The gastric secretion of IF, acid, and pepsin during basal conditions and stimulation by pentagastrin decreased significantly in 8 unoperated duodenal ulcer patients following administration of atropine. The basal concentrations of acid and pepsin decreased, whereas that of IF remained unchanged. An increase of plasma gastrin concentration from the basal value was observed after injection of atropine alone. The secretions of IF and acid decreased significantly from the pre-operative values after proximal gastric vagotomy in 7 duodenal ulcer patients. The basal IF output decreased by 19.8 per cent and the stimulated output by 41.4 per cent. The basal and stimulated secretions of acid decreased by 50.0 and 44.1 per cent, respectively. It is suggested that the smaller reduction of IF than of acid may be of importance for the vitamin B12 absorption after vagotomy. The decreased secretion of IF was secondary to the reduction of volume both after'medical' and surgical vagotomy."}
{"id": "PMID:235786", "title": "Intragastric pressure/volume relationship before and after proximal gastric vagotomy.", "content": "The examinations were performed before and after proximal gastric vagotomy (PGV) in 10 patients with duodenal ulcer. A flaccid plastic balloon located in the corpus-fundus region was stepwise filled with known volumes of water. Post-operative insulin tests were negative in 8 patients and late positive in two. Basal and pentagastrin-stimulated acid output were reduced by a mean of 88 and 62 percent, respectively. Intragastric pressure was significantly increased after PGV, whereas rhythmic contractions were reduced in all cases. It is concluded that PGV interferes with gastric motility and adaptation to volume variations.", "contents": "Intragastric pressure/volume relationship before and after proximal gastric vagotomy. The examinations were performed before and after proximal gastric vagotomy (PGV) in 10 patients with duodenal ulcer. A flaccid plastic balloon located in the corpus-fundus region was stepwise filled with known volumes of water. Post-operative insulin tests were negative in 8 patients and late positive in two. Basal and pentagastrin-stimulated acid output were reduced by a mean of 88 and 62 percent, respectively. Intragastric pressure was significantly increased after PGV, whereas rhythmic contractions were reduced in all cases. It is concluded that PGV interferes with gastric motility and adaptation to volume variations."}
{"id": "PMID:235787", "title": "Gastric acid response to antrum distension in man.", "content": "Gastric acid secretion under basal conditions and in response to graded balloon distension (50 ml, 100 ml, 150 ml) of the antrum was determined in healthy subjects and in peptic ulcer patients. In patients with a quiescent duodenal ulcer or a gastric ulcer antrum distension produced slight acid responses. The acid response to antrum distension was of quantitative importance only in patients with an active duodenal ulcer, amounting to 35 percent of the maximal acid response to pentagastrin. The healthy subjects did not respond with acid secretion to antrum distension. The pH of the gastric contents in the present series was 1.8-3.0, being lowest in patients with an active duodenal ulcer. Thus, the acid secretory effect of mechanical stimulation of the antrum seems qualitatively different in healthy subjects and ulcer patients, with a marked acid response in patients with an active duodenal ulcer.", "contents": "Gastric acid response to antrum distension in man. Gastric acid secretion under basal conditions and in response to graded balloon distension (50 ml, 100 ml, 150 ml) of the antrum was determined in healthy subjects and in peptic ulcer patients. In patients with a quiescent duodenal ulcer or a gastric ulcer antrum distension produced slight acid responses. The acid response to antrum distension was of quantitative importance only in patients with an active duodenal ulcer, amounting to 35 percent of the maximal acid response to pentagastrin. The healthy subjects did not respond with acid secretion to antrum distension. The pH of the gastric contents in the present series was 1.8-3.0, being lowest in patients with an active duodenal ulcer. Thus, the acid secretory effect of mechanical stimulation of the antrum seems qualitatively different in healthy subjects and ulcer patients, with a marked acid response in patients with an active duodenal ulcer."}
{"id": "PMID:235789", "title": "[Thyreotoxic crisis triggered by stimulation of the adrenal gland medulla].", "content": "Thyroid storm was observed in a patient with Grave's disease after stimulation of release of epinephrine and norepinephrine with 2-DG. Measurements of catecholamine secretion before and during onset of thyrotoxic crisis suggested the important bearing of increased activity of the sympathetic nervous system on pathogenesis of thyroid storm.", "contents": "[Thyreotoxic crisis triggered by stimulation of the adrenal gland medulla]. Thyroid storm was observed in a patient with Grave's disease after stimulation of release of epinephrine and norepinephrine with 2-DG. Measurements of catecholamine secretion before and during onset of thyrotoxic crisis suggested the important bearing of increased activity of the sympathetic nervous system on pathogenesis of thyroid storm."}
{"id": "PMID:235791", "title": "Influence of the ionic composition of the medium on the sensitivity of fertilized sea urchin ova to neuropharmacological preparations.", "content": "The removal of Ca2+ from the incubation medium leads to an increase in the sensitivity of early sea urchin embryos to neuropharmacological blockers of development. The removal of SO4-2-, half of the K+, as well as an increase in the Ca2+ content, have no effect on the sensitivity of fertilized eggs to these preparations. The sensitivity to puromycin, colchicine, triton X-100, and 2, 4-dinitrophenol is unchanged by the removal of Ca2+ from the medium. The protective action of exogenous monoamines and acetylcholine is not manifested in a solution that does not contain Ca2+. Serotonin, catecholamines, and acetylcholine have no appreciable effect on cleavage either in sea water of normal composition or in water without Ca2+.", "contents": "Influence of the ionic composition of the medium on the sensitivity of fertilized sea urchin ova to neuropharmacological preparations. The removal of Ca2+ from the incubation medium leads to an increase in the sensitivity of early sea urchin embryos to neuropharmacological blockers of development. The removal of SO4-2-, half of the K+, as well as an increase in the Ca2+ content, have no effect on the sensitivity of fertilized eggs to these preparations. The sensitivity to puromycin, colchicine, triton X-100, and 2, 4-dinitrophenol is unchanged by the removal of Ca2+ from the medium. The protective action of exogenous monoamines and acetylcholine is not manifested in a solution that does not contain Ca2+. Serotonin, catecholamines, and acetylcholine have no appreciable effect on cleavage either in sea water of normal composition or in water without Ca2+."}
{"id": "PMID:235792", "title": "Chromatographic separation of pigments produced by Arthroderma benhamiae.", "content": "Variations in pigment production under different cultural conditions have limited the usefulness of pigmentation for identifying strains of Arthroderma benhamiae. If culture conditions are constant, pigmentation by individual strains is reproducible, and may be extracted and separated by thin layer chromatography. This allows recognition of pigment similarities which may be masked in whole colonies, thereby greatly enhancing the value of pigmentation in strain identification.", "contents": "Chromatographic separation of pigments produced by Arthroderma benhamiae. Variations in pigment production under different cultural conditions have limited the usefulness of pigmentation for identifying strains of Arthroderma benhamiae. If culture conditions are constant, pigmentation by individual strains is reproducible, and may be extracted and separated by thin layer chromatography. This allows recognition of pigment similarities which may be masked in whole colonies, thereby greatly enhancing the value of pigmentation in strain identification."}
{"id": "PMID:235794", "title": "Effect of ischemic anoxia on myoelectrical and mechanical activity of the totally isolated canine stomach.", "content": "Electrical and mechanical activities were recorded from the totally isolated canine stomach perfused with homologous blood of a living oxygenator-supported dog. Stagnant ischemic anoxia was induced by closing inflow and outflow blood from the isolated organ for various periods of time up to four hours. Recording of electrical and mechanical activity was performed prior to, during, and after the anoxic periods. After a given period of ischemia, blood was recirculated for ten minutes, and the pentagastrin was injected into the gastric artery. After up to three hours of anoxia, stomachs were able to show recordable electrical activity when perfused for ten minutes with homologous blood. Up to this period of three hours, stomachs also responded to the injection of pentagastrin. Pentagastrin accelerated the normalization of electrical and mechanical activity of previously anoxic stomachs. After 3.5 to 4.0 hours of anoxia, recirculation of blood through the stomach and injection of pentagastrin had no effect on electrical and mechanical activity of the gastric musculature.", "contents": "Effect of ischemic anoxia on myoelectrical and mechanical activity of the totally isolated canine stomach. Electrical and mechanical activities were recorded from the totally isolated canine stomach perfused with homologous blood of a living oxygenator-supported dog. Stagnant ischemic anoxia was induced by closing inflow and outflow blood from the isolated organ for various periods of time up to four hours. Recording of electrical and mechanical activity was performed prior to, during, and after the anoxic periods. After a given period of ischemia, blood was recirculated for ten minutes, and the pentagastrin was injected into the gastric artery. After up to three hours of anoxia, stomachs were able to show recordable electrical activity when perfused for ten minutes with homologous blood. Up to this period of three hours, stomachs also responded to the injection of pentagastrin. Pentagastrin accelerated the normalization of electrical and mechanical activity of previously anoxic stomachs. After 3.5 to 4.0 hours of anoxia, recirculation of blood through the stomach and injection of pentagastrin had no effect on electrical and mechanical activity of the gastric musculature."}
{"id": "PMID:235795", "title": "Heart transplantation in endotoxin shock.", "content": "The condition of the heart from dogs in endotoxin shock was evaluated, and all dogs in the control group receiving 5 milligrams per kilogram to Eschericia coli endotoxin died within two to 14 hours. Hearts from four other dogs receiving the same dosage of endotoxin were allografted orthotopically into healthy recipient dogs. The donor heart was taken in the terminal phase of shock, after the blood pressure of the donor had declined to 50 millimeters of mercury or less. All four heart allografts functioned normally in the healthy hosts, demonstrating that lethal levels of gram-negative endotoxin do not produce direct irreversible damage to the myocardium or to the conduction mechanism of the heart. This also was shown in one pair of monkeys; the donor monkey had received ten times the dosage of endotoxin used in the dogs. This heart transplant model offers considerable advantage in functional studies of the heart after irreversible shock.", "contents": "Heart transplantation in endotoxin shock. The condition of the heart from dogs in endotoxin shock was evaluated, and all dogs in the control group receiving 5 milligrams per kilogram to Eschericia coli endotoxin died within two to 14 hours. Hearts from four other dogs receiving the same dosage of endotoxin were allografted orthotopically into healthy recipient dogs. The donor heart was taken in the terminal phase of shock, after the blood pressure of the donor had declined to 50 millimeters of mercury or less. All four heart allografts functioned normally in the healthy hosts, demonstrating that lethal levels of gram-negative endotoxin do not produce direct irreversible damage to the myocardium or to the conduction mechanism of the heart. This also was shown in one pair of monkeys; the donor monkey had received ten times the dosage of endotoxin used in the dogs. This heart transplant model offers considerable advantage in functional studies of the heart after irreversible shock."}
{"id": "PMID:235796", "title": "Spontaneous rupture of the liver and the spleen: report of a successfully treated case with immunopathologic reaction.", "content": "A patient with a spontaneous rupture of the liver, followed by a spontaneous rupture of the spleen and gastrointestinal bleeding, is reported. The patient was operated for both ruptures and survived. We could not find any corresponding reports in the literature. Histological findings both in the liver and in the spleen were suggestive of an acute immunologic reaction and the symptoms of the patient resembled those of an autoimmune disease. Attention is drawn to the possibility that the ruptures of the liver and the spleen might have represented an allergic reaction reminiscent of the general type of Schwartzman reaction. This also could explain the other systemic manifestations of the disease. In the present patient steroid therapy eliminated all symptoms, and this possibility should be kept in mind when treating obscure ruptures of the liver and the spleen.", "contents": "Spontaneous rupture of the liver and the spleen: report of a successfully treated case with immunopathologic reaction. A patient with a spontaneous rupture of the liver, followed by a spontaneous rupture of the spleen and gastrointestinal bleeding, is reported. The patient was operated for both ruptures and survived. We could not find any corresponding reports in the literature. Histological findings both in the liver and in the spleen were suggestive of an acute immunologic reaction and the symptoms of the patient resembled those of an autoimmune disease. Attention is drawn to the possibility that the ruptures of the liver and the spleen might have represented an allergic reaction reminiscent of the general type of Schwartzman reaction. This also could explain the other systemic manifestations of the disease. In the present patient steroid therapy eliminated all symptoms, and this possibility should be kept in mind when treating obscure ruptures of the liver and the spleen."}
{"id": "PMID:235801", "title": "Analysis of results of catheter tip cultures in open-heart surgery patients.", "content": "A statistical analysis of 628 consecutive catheter tip cultures is presented. All were from patients undergoing open-heart surgery. The previously noted effects of early removal are shown to be significant. The possible effects of stasis, flushing, handling, and place of insertion are discussed. The unresolved significance of isolations of aerobic sporing bacilli is noted, and a decreasing incidence of postoperative infective endocarditis in the same group of patients is an encouraging sign.", "contents": "Analysis of results of catheter tip cultures in open-heart surgery patients. A statistical analysis of 628 consecutive catheter tip cultures is presented. All were from patients undergoing open-heart surgery. The previously noted effects of early removal are shown to be significant. The possible effects of stasis, flushing, handling, and place of insertion are discussed. The unresolved significance of isolations of aerobic sporing bacilli is noted, and a decreasing incidence of postoperative infective endocarditis in the same group of patients is an encouraging sign."}
{"id": "PMID:235802", "title": "The lungs in renal failure.", "content": "Pulmonary function was studied in 55 patients with renal failure and no clinical or radiographic evidence of lung disease. A defect of gas transfer was found to be the rule due to a reduction in the diffusing capacity across the alveolar capillary membrane; this abnormality appeared to be related to the severity of the renal impairment. There was also a restrictive ventilatory defect which was more marked in male than in female patients. The significance of these findings is discussed, and attention is drawn to their relevance for patients receiving immuno-suppressive therapy or renal transplantation, in whom pulmonary complications are relatively common.", "contents": "The lungs in renal failure. Pulmonary function was studied in 55 patients with renal failure and no clinical or radiographic evidence of lung disease. A defect of gas transfer was found to be the rule due to a reduction in the diffusing capacity across the alveolar capillary membrane; this abnormality appeared to be related to the severity of the renal impairment. There was also a restrictive ventilatory defect which was more marked in male than in female patients. The significance of these findings is discussed, and attention is drawn to their relevance for patients receiving immuno-suppressive therapy or renal transplantation, in whom pulmonary complications are relatively common."}
{"id": "PMID:235803", "title": "Comparative effects of beta adrenergic blocking drugs.", "content": "Although many different beta blockers are now in clinical use, there is very little information concerning their relative efficacy, and it is still not clear what clinical importance should be attached to properties such as positive inotropic stimulation (intrinsic sympathomimetic activity or ISA) and membrane stabilizing action (\"local anaesthetic effect\" or \"quinidine-like effect\"). In this report we compare the ability of patients with angina to exercise on a bicycle ergometer while receiving a series of commonly used beta blockers, and attempt to determine the importance of ISA. The investigation is in four parts with the drugs given orally or intravenously: statistical analysis of the results was carried out using standard methods, both parametric and non-parametric (Friedmann analysis of variance, Wilcoxon matched pairs signed ranks test) by two independent statisticians. The relevant properties of drugs included in this paper are summarized in Table I. Laboratory reports using many different animal preparations may differ from this assessment under specific conditions, and the Table is intended only as a guide to the generally accepted properties of these drugs when used clinically. Results for sotalol are included for reference in the first part of this paper but the drug was withdrawn from clinical use and was not studied further.", "contents": "Comparative effects of beta adrenergic blocking drugs. Although many different beta blockers are now in clinical use, there is very little information concerning their relative efficacy, and it is still not clear what clinical importance should be attached to properties such as positive inotropic stimulation (intrinsic sympathomimetic activity or ISA) and membrane stabilizing action (\"local anaesthetic effect\" or \"quinidine-like effect\"). In this report we compare the ability of patients with angina to exercise on a bicycle ergometer while receiving a series of commonly used beta blockers, and attempt to determine the importance of ISA. The investigation is in four parts with the drugs given orally or intravenously: statistical analysis of the results was carried out using standard methods, both parametric and non-parametric (Friedmann analysis of variance, Wilcoxon matched pairs signed ranks test) by two independent statisticians. The relevant properties of drugs included in this paper are summarized in Table I. Laboratory reports using many different animal preparations may differ from this assessment under specific conditions, and the Table is intended only as a guide to the generally accepted properties of these drugs when used clinically. Results for sotalol are included for reference in the first part of this paper but the drug was withdrawn from clinical use and was not studied further."}
{"id": "PMID:235808", "title": "Toxicity of aerosol propellants in the respiratory and circulatory systems. VI. Influence of cardiac and pulmonary vascular lesions in the rat.", "content": "Three propellants were selected for investigation in rats because of their non-uniform effect in mice and monkeys. Trichlorofluoromethane (FC 11) provoked arrhythmia in all three animal species, dichlorodifluoromethane (FC 12) in monkeys and rats but not in mice, and difluoroethane (FC 152a) only in rats. In rats the alterations in heart rate and electrocardiographic pattern during inhalation of these propellants are largely brought about by release of catecholamines from the adrenal gland, because adrenalectomy or prior injection of beta-adrenergic blocking drugs decreased the incidence of cardiac effects. Rats that have pulmonary vascular thrombosis or cardiac necrosis become more sensitive to proarrhythmic activity of these propellants.", "contents": "Toxicity of aerosol propellants in the respiratory and circulatory systems. VI. Influence of cardiac and pulmonary vascular lesions in the rat. Three propellants were selected for investigation in rats because of their non-uniform effect in mice and monkeys. Trichlorofluoromethane (FC 11) provoked arrhythmia in all three animal species, dichlorodifluoromethane (FC 12) in monkeys and rats but not in mice, and difluoroethane (FC 152a) only in rats. In rats the alterations in heart rate and electrocardiographic pattern during inhalation of these propellants are largely brought about by release of catecholamines from the adrenal gland, because adrenalectomy or prior injection of beta-adrenergic blocking drugs decreased the incidence of cardiac effects. Rats that have pulmonary vascular thrombosis or cardiac necrosis become more sensitive to proarrhythmic activity of these propellants."}
{"id": "PMID:235809", "title": "Toxicity of aerosol propellants in the respiratory and circulatory systems. VII. Influence of pulmonary emphysema and anesthesia in the rat.", "content": "Experimental induction of pulmonary emphysema caused an increase in sensitivity of the rat to toxicity from inhalation of propellants. The emphysematous rat showed an exaggerated reduction in pulmonary compliance in response to inhalation of trichlorofluoromethane (FC 11). In emphysematous and non emphysematous rats without anesthesia the inhalation of FC 11 caused tachycardia, arrhythmias and other abnormalities in the electrocardiogram. The tachycardiac response was eliminated by induction of barbiturate anesthesia, which increased the sensitivity of the heart to occurrence of abnormalities in the electrocardiogram in response to inhalation of FC 11 as well as of dichlorodifluoromethane (FC 12) and difluoroethane (FC 152a). The acceleration in heart rate in response to inhalation of FC 11, hypoxia or hypercapnea was prevented by prior treatment with a beta-blocking drug.", "contents": "Toxicity of aerosol propellants in the respiratory and circulatory systems. VII. Influence of pulmonary emphysema and anesthesia in the rat. Experimental induction of pulmonary emphysema caused an increase in sensitivity of the rat to toxicity from inhalation of propellants. The emphysematous rat showed an exaggerated reduction in pulmonary compliance in response to inhalation of trichlorofluoromethane (FC 11). In emphysematous and non emphysematous rats without anesthesia the inhalation of FC 11 caused tachycardia, arrhythmias and other abnormalities in the electrocardiogram. The tachycardiac response was eliminated by induction of barbiturate anesthesia, which increased the sensitivity of the heart to occurrence of abnormalities in the electrocardiogram in response to inhalation of FC 11 as well as of dichlorodifluoromethane (FC 12) and difluoroethane (FC 152a). The acceleration in heart rate in response to inhalation of FC 11, hypoxia or hypercapnea was prevented by prior treatment with a beta-blocking drug."}
{"id": "PMID:235812", "title": "Immunological aspects of the acquired B antigen.", "content": "Nine cases of acquired B antigen were studied. By quantitative methods the variation of the A reactivity and of the number of A sites was found to be inversely related to the variation of the B reactivity. By agglutination kinetics using an immune anti-B, the acquired B reactive structure was found to differ from that of a normal B. Agglutination variation, with pH, points out to the part played by one electrically charged chemical group. No transferase galactosyl activity was found in the serum, and no B substance in the plasma. According to these results the B reactive structure must have been formed at the expense of the A reactive structure. This \"acquired B\" type may have arisen as a result of the action of a bacterial deacetylase, transforming the A reactive N-acetyl galactosamine into galactosamine.", "contents": "Immunological aspects of the acquired B antigen. Nine cases of acquired B antigen were studied. By quantitative methods the variation of the A reactivity and of the number of A sites was found to be inversely related to the variation of the B reactivity. By agglutination kinetics using an immune anti-B, the acquired B reactive structure was found to differ from that of a normal B. Agglutination variation, with pH, points out to the part played by one electrically charged chemical group. No transferase galactosyl activity was found in the serum, and no B substance in the plasma. According to these results the B reactive structure must have been formed at the expense of the A reactive structure. This \"acquired B\" type may have arisen as a result of the action of a bacterial deacetylase, transforming the A reactive N-acetyl galactosamine into galactosamine."}
{"id": "PMID:235815", "title": "True Arrhenius relationships of human lactate dehydrogenase.", "content": "The pyruvate and NADH concentrations and the buffer pH which gave maximal activity with LDH isoenzymes derived from human heart and liver tissue were established for the temperatures 25 degrees C, 30 degrees C, 35 degrees C, 37 degrees C,, 40 degrees C, 45 degrees C, and 50 degrees C. The velocities of the LDH isoenzymes using these maximal assay conditions were used to obtain Arrhenius plots, i.e. log initial velocity against inverse absolute temperature. The Arrhenius plots were linear with both isoenzyme preparations up to 45 degrees C. Between 45 degrees C and 50 degrees C it appeared that this linear relationship no longer held, particularly with the liver tissue. When the activation energies were calculated both isoenzyme preparations exhibited several points of inflexion, in each case occuring at the same temperatures. These inflexions represent a change in the reaction kinetics, possibly a conformational change in the enzyme. The results also indicate that the LDH 1 and 2 isoenzymes are more efficient than LDH 4 and 5.", "contents": "True Arrhenius relationships of human lactate dehydrogenase. The pyruvate and NADH concentrations and the buffer pH which gave maximal activity with LDH isoenzymes derived from human heart and liver tissue were established for the temperatures 25 degrees C, 30 degrees C, 35 degrees C, 37 degrees C,, 40 degrees C, 45 degrees C, and 50 degrees C. The velocities of the LDH isoenzymes using these maximal assay conditions were used to obtain Arrhenius plots, i.e. log initial velocity against inverse absolute temperature. The Arrhenius plots were linear with both isoenzyme preparations up to 45 degrees C. Between 45 degrees C and 50 degrees C it appeared that this linear relationship no longer held, particularly with the liver tissue. When the activation energies were calculated both isoenzyme preparations exhibited several points of inflexion, in each case occuring at the same temperatures. These inflexions represent a change in the reaction kinetics, possibly a conformational change in the enzyme. The results also indicate that the LDH 1 and 2 isoenzymes are more efficient than LDH 4 and 5."}
{"id": "PMID:235816", "title": "[Calculation of the parameters of the acid-base balance with the aid of a small computer].", "content": "The application and modification of a program published by Hardt (1972), Clin. Chem. 18,658--661) for the calculation of the true pCO2, the standard bicarbonate and the base excess are reported. 217 Determinations of a random patient sample were evaluated graphically, with the aid of a nomogram of Siggaard-Andersen, and mathematically with a computer program. There was good agreement between the two evaluation methods.", "contents": "[Calculation of the parameters of the acid-base balance with the aid of a small computer]. The application and modification of a program published by Hardt (1972), Clin. Chem. 18,658--661) for the calculation of the true pCO2, the standard bicarbonate and the base excess are reported. 217 Determinations of a random patient sample were evaluated graphically, with the aid of a nomogram of Siggaard-Andersen, and mathematically with a computer program. There was good agreement between the two evaluation methods."}
{"id": "PMID:235820", "title": "[Sialic acid in F. tularensis and F. novicida antigens].", "content": "Sialic acid was revealed in the antigens of virulent (503/830 and Schu) and vaccine (Schu-attenuated and 15-reduced) strains of F. tularensis and also in the antigens of F. novicida isolated by the treatment with trichloracetic acid, by the thiobarbiturate method of Warren. Its content depended on the culture virulence. Sialic acid was absent in the antigens of avirulent strains of the causative agent of tularemia (503-attenuated, 15-attenuated and 21/400), but, in difference from the virulent strains, there was revealed 2-desoxyribose on account of the presence of DNA. Serological activity of F. tularensis antigen decreased only 15 times in the antibody neutralization reaction after a complete release of sialic acid as a result of hydrolysis of the preparation in 0.1 N, H2SO4 at 80 degrees C for one hour, i.e. it persisted at a sufficiently high level. On the basis of investigations carried out it can be admitted that there existed a chemical association between the sialic acid and other composites in the polysaccharide of the virulent and the vaccine strains of F. tularensis, but that this acid played no significant role in the manifestation of specific properties by the antigen.", "contents": "[Sialic acid in F. tularensis and F. novicida antigens]. Sialic acid was revealed in the antigens of virulent (503/830 and Schu) and vaccine (Schu-attenuated and 15-reduced) strains of F. tularensis and also in the antigens of F. novicida isolated by the treatment with trichloracetic acid, by the thiobarbiturate method of Warren. Its content depended on the culture virulence. Sialic acid was absent in the antigens of avirulent strains of the causative agent of tularemia (503-attenuated, 15-attenuated and 21/400), but, in difference from the virulent strains, there was revealed 2-desoxyribose on account of the presence of DNA. Serological activity of F. tularensis antigen decreased only 15 times in the antibody neutralization reaction after a complete release of sialic acid as a result of hydrolysis of the preparation in 0.1 N, H2SO4 at 80 degrees C for one hour, i.e. it persisted at a sufficiently high level. On the basis of investigations carried out it can be admitted that there existed a chemical association between the sialic acid and other composites in the polysaccharide of the virulent and the vaccine strains of F. tularensis, but that this acid played no significant role in the manifestation of specific properties by the antigen."}
{"id": "PMID:235821", "title": "[Identification of mycoplasmas isolated from monkeys].", "content": "The authors identified 15 strains of mycoplasmae isolated from Papio hamadryas suffering from leukemia and from healthy Macacus rhesus, a green monkey and saimiri. A study was made of their biochemical properties, antigenic properties in the reaction of growth depression with immune sera to a number of standard strains, and also the protein composition by electrophoresis in polyacrylamide gel (EPAG). A number of mycoplasmae were identified as A. laidlawii, M. arthritidis--Campo and M. cynomolgus KI, affilated to M. orale II. Four strains were apparently a mixture of three mycoplasmae (M. cynomolgus KI, M. arthritidis--Campo, and M. hyorhinis). Six strains of mycoplasmae (three enzymatically active, belonging according to EPAG data to a single serological type, and three--enzymatically inert, differing by EPAG) could not be identified.", "contents": "[Identification of mycoplasmas isolated from monkeys]. The authors identified 15 strains of mycoplasmae isolated from Papio hamadryas suffering from leukemia and from healthy Macacus rhesus, a green monkey and saimiri. A study was made of their biochemical properties, antigenic properties in the reaction of growth depression with immune sera to a number of standard strains, and also the protein composition by electrophoresis in polyacrylamide gel (EPAG). A number of mycoplasmae were identified as A. laidlawii, M. arthritidis--Campo and M. cynomolgus KI, affilated to M. orale II. Four strains were apparently a mixture of three mycoplasmae (M. cynomolgus KI, M. arthritidis--Campo, and M. hyorhinis). Six strains of mycoplasmae (three enzymatically active, belonging according to EPAG data to a single serological type, and three--enzymatically inert, differing by EPAG) could not be identified."}
{"id": "PMID:235822", "title": "[The possibility of predicting the degree of plasmacyte reaction in response to administration of soluble antigen to mice].", "content": "The work is devoted to the mathematical description of the accumulation of plasma cells in the spleen of CBA mice immunized intraperitoneally. A dependence between the dynamics of the soluble antigen concentration in the blood and the plasmocytic reaction in the spleen was confirmed under experimental conditions. Index A was suggested for detection of a change from the antigenic function to the accumulation of plasma cells. The mean values of index A were used to compare the calculated values of the plasmocytic reaction and the experimental data; differences between these values were insignificant. Analogously index A was used for predicting the accumulation of plasma cells in the animals to which a mixture of the two soluble antigens (a capsular antigen of the causative agent of plague and a complete antigen of the causative agent of tularemia) was administered. The calculated values of the plasmocytic reaction in this experiment satisfactorily correlated with the data obtained experimentally.", "contents": "[The possibility of predicting the degree of plasmacyte reaction in response to administration of soluble antigen to mice]. The work is devoted to the mathematical description of the accumulation of plasma cells in the spleen of CBA mice immunized intraperitoneally. A dependence between the dynamics of the soluble antigen concentration in the blood and the plasmocytic reaction in the spleen was confirmed under experimental conditions. Index A was suggested for detection of a change from the antigenic function to the accumulation of plasma cells. The mean values of index A were used to compare the calculated values of the plasmocytic reaction and the experimental data; differences between these values were insignificant. Analogously index A was used for predicting the accumulation of plasma cells in the animals to which a mixture of the two soluble antigens (a capsular antigen of the causative agent of plague and a complete antigen of the causative agent of tularemia) was administered. The calculated values of the plasmocytic reaction in this experiment satisfactorily correlated with the data obtained experimentally."}
{"id": "PMID:235823", "title": "Chemical dissection of mammalian spermatozoa.", "content": "Mammalian spermatozoa have been dissected by a variety of chemical techniques to yield free heads, tails with attached midpieces, and tails without mitochondria. By brief exposure to trypsin, mouse and rat spermatozoa were cleaved at the junction of the head and the tail, while human, guinea pig and rabbit spermatozoa were cleaved by trypsin only after prior incubation with a sulphhydryl reducing agent. Treatment with acid or base cleaved spermatozoa of all species examined. In contrast, exposure of spermatozoa to 1% sarkosyl NL-97 resulted in the quantitative cleavage of mouse cells without noticeable effect on the spermatozoa of the other species. Mitochondria were removed from the midpiece of intact sperm and isolated tails by gentle shaking after treatment with reducing agents. Homogeneous populations of spermatozoan subcellular components were obtained by density gradient centrifugation. Ultrastructural analysis showed that cleavage of mouse spermatozoa by trypsin occurs at a specific location in the neck of the cell without trypsin occurs at a specific location in the neck of the cell without observable damage to other cell structures. The basal plate remained attached to the head structures. In contrast cleavage of spermatozoa by sarkosyl or acid left the basal plate attached to the spermatozoan midpiece. Sarkosyl also removed the plasma membrane and extracted mitochondrial components. Treatment with acid or base also resulted in vesiculation of the plasma membrane and dissolution of the acrosome. Molecular probes have also been used to facilitate mapping of the cell surface. Each mouse spermatozoon has about 10-7 receptors for the lectin concanavalin A. Binding of fluorescein-labelled concanavalin A indicated that the majority of the receptors is in the acrosomal region; this polar distribution was confirmed by measurement of the number of sites on purified heads and tails. In addition, the low molecular weight probe ANS bound to the plasma membrane of spermatozoa from all species examined, with immediate immobilization of the cells. Ethidium bromide bound to the spermatozoan head without affecting motility.", "contents": "Chemical dissection of mammalian spermatozoa. Mammalian spermatozoa have been dissected by a variety of chemical techniques to yield free heads, tails with attached midpieces, and tails without mitochondria. By brief exposure to trypsin, mouse and rat spermatozoa were cleaved at the junction of the head and the tail, while human, guinea pig and rabbit spermatozoa were cleaved by trypsin only after prior incubation with a sulphhydryl reducing agent. Treatment with acid or base cleaved spermatozoa of all species examined. In contrast, exposure of spermatozoa to 1% sarkosyl NL-97 resulted in the quantitative cleavage of mouse cells without noticeable effect on the spermatozoa of the other species. Mitochondria were removed from the midpiece of intact sperm and isolated tails by gentle shaking after treatment with reducing agents. Homogeneous populations of spermatozoan subcellular components were obtained by density gradient centrifugation. Ultrastructural analysis showed that cleavage of mouse spermatozoa by trypsin occurs at a specific location in the neck of the cell without trypsin occurs at a specific location in the neck of the cell without observable damage to other cell structures. The basal plate remained attached to the head structures. In contrast cleavage of spermatozoa by sarkosyl or acid left the basal plate attached to the spermatozoan midpiece. Sarkosyl also removed the plasma membrane and extracted mitochondrial components. Treatment with acid or base also resulted in vesiculation of the plasma membrane and dissolution of the acrosome. Molecular probes have also been used to facilitate mapping of the cell surface. Each mouse spermatozoon has about 10-7 receptors for the lectin concanavalin A. Binding of fluorescein-labelled concanavalin A indicated that the majority of the receptors is in the acrosomal region; this polar distribution was confirmed by measurement of the number of sites on purified heads and tails. In addition, the low molecular weight probe ANS bound to the plasma membrane of spermatozoa from all species examined, with immediate immobilization of the cells. Ethidium bromide bound to the spermatozoan head without affecting motility."}
{"id": "PMID:235824", "title": "Fibrinoid necrosis of liver parenchymal cells.", "content": "By means of different histological and histochemical investigations and fluorescence microscopy it has been possible to demonstrate fibrinoid necrosis of parenchymal liver cells in cases of delayed chloroform death and in septic, toxic and infectious hepatitis. This type of necrosis has previously been observed only in connective tissue and in vessel walls, in particular in collagenoses. It was also possible to provoke this type of liver cell necrosis in animal experiments. Reference has been made to differences in the chemical composition of the fibrinoid substance and to relations to other related substances (amyloid, keratin, fibrin). The importance of fluorescence microscopic invesitgations with fluorochromes, using Novelli's method, and with certain other procedures is emphasized.", "contents": "Fibrinoid necrosis of liver parenchymal cells. By means of different histological and histochemical investigations and fluorescence microscopy it has been possible to demonstrate fibrinoid necrosis of parenchymal liver cells in cases of delayed chloroform death and in septic, toxic and infectious hepatitis. This type of necrosis has previously been observed only in connective tissue and in vessel walls, in particular in collagenoses. It was also possible to provoke this type of liver cell necrosis in animal experiments. Reference has been made to differences in the chemical composition of the fibrinoid substance and to relations to other related substances (amyloid, keratin, fibrin). The importance of fluorescence microscopic invesitgations with fluorochromes, using Novelli's method, and with certain other procedures is emphasized."}
{"id": "PMID:235825", "title": "Subcellular distribution of amino acid naphthylamidase isozymes in human leucocytes.", "content": "Three isozymes (A, B and C) of amino acid naphthylamidase were found in human leucocytes. Isozyme B and C had close biochemical similarities and differed from isozyme A. Isozyme A was localized in the cytosol. Results obtained by combining electrophoresis with gradient centrifugation suggested that isozyme B originated in granules of polymorphonuclear leucocytes enriched in alkaline phosphatase. Isozyme C was found in granules of low density of polymorphonuclear as well as mononuclear leucocytes.", "contents": "Subcellular distribution of amino acid naphthylamidase isozymes in human leucocytes. Three isozymes (A, B and C) of amino acid naphthylamidase were found in human leucocytes. Isozyme B and C had close biochemical similarities and differed from isozyme A. Isozyme A was localized in the cytosol. Results obtained by combining electrophoresis with gradient centrifugation suggested that isozyme B originated in granules of polymorphonuclear leucocytes enriched in alkaline phosphatase. Isozyme C was found in granules of low density of polymorphonuclear as well as mononuclear leucocytes."}
{"id": "PMID:235827", "title": "Natural antibodies in healthy adults.", "content": "The serum of 100 adults living in Budapest was examined for isohaemagglutinin titre with haemaglutination, for staphylococcal-antitoxin titre with haemolysis inhibition and for bacterial antibody titre against 17 different groups of bacteria with passive haemagglutination. Antibody levels in males, except for certain bacterial antibodies, were somewhat lower than in females. The antibody titres, especially in men, decreased gradually from 20 to 50 years of age and were usually lower in Rh negative than in Rh positive persons.", "contents": "Natural antibodies in healthy adults. The serum of 100 adults living in Budapest was examined for isohaemagglutinin titre with haemaglutination, for staphylococcal-antitoxin titre with haemolysis inhibition and for bacterial antibody titre against 17 different groups of bacteria with passive haemagglutination. Antibody levels in males, except for certain bacterial antibodies, were somewhat lower than in females. The antibody titres, especially in men, decreased gradually from 20 to 50 years of age and were usually lower in Rh negative than in Rh positive persons."}
{"id": "PMID:235826", "title": "The thyroid in ulcerative colitis and Crohn's disease. I. Thyroid radioiodide uptake and urinary iodine excretion.", "content": "In order to investigate the prevalence of iodine depletion in chronic inflammatory bowel disease two separate studies have been performed. One was devoted to the 24-hour urinary iodine excretion and 50 patients with ulcerative colitis or Crohn's disease were examined and compared with 102 controls. In the other study the thyroid 131I uptake was compared in 38 patients and 36 controls. Ten of the 50 patients with chronic inflammatory bowel disease had a 24-hour urinary iodine excretion less than 40 mug, compared with 5 of the 102 controls (p greater than 0.01). Sixteen of the 38 patients had a 24-hour thyroid 131I uptake of 50% or more of the administered test does, compared with 4 of the 36 controls (p smaller than 0.01). These results are compatible with an increased occurrence of iodine deficiency in patients with chronic inflammatory bowel disease. Treatment with corticosteroids or Salazopyrin or a milk-free diet did not influence these findings. No evidence was found of an impaired absorption of inorganic iodide from the gut.?31", "contents": "The thyroid in ulcerative colitis and Crohn's disease. I. Thyroid radioiodide uptake and urinary iodine excretion. In order to investigate the prevalence of iodine depletion in chronic inflammatory bowel disease two separate studies have been performed. One was devoted to the 24-hour urinary iodine excretion and 50 patients with ulcerative colitis or Crohn's disease were examined and compared with 102 controls. In the other study the thyroid 131I uptake was compared in 38 patients and 36 controls. Ten of the 50 patients with chronic inflammatory bowel disease had a 24-hour urinary iodine excretion less than 40 mug, compared with 5 of the 102 controls (p greater than 0.01). Sixteen of the 38 patients had a 24-hour thyroid 131I uptake of 50% or more of the administered test does, compared with 4 of the 36 controls (p smaller than 0.01). These results are compatible with an increased occurrence of iodine deficiency in patients with chronic inflammatory bowel disease. Treatment with corticosteroids or Salazopyrin or a milk-free diet did not influence these findings. No evidence was found of an impaired absorption of inorganic iodide from the gut.?31"}
{"id": "PMID:235834", "title": "Circulatory effects of tazolol in experimental myocardial infarction.", "content": "The hemodynamic effects of tazolol, a new long-acting beta-stimulating drug, were studied in dogs with acute pump failure caused by experimental myocardial infarction and the results were compared with the actions of isoproterenol given in small and large doses. Tazolol produced a significant and sustained increase in cardiac output and stroke volume, while causing a decrease in peripheral resistance and mean aortic pressure. Heart rate was only modestly increased. Compared with isoproterenol at equivalent doses. tazolol appeared to cause less S-T segment elevation at the margin of infarction. The increase in double product (systolic pressure X heart rate) produced by tazolol was also considerably less than that of isoproterenol. Tazolol may prove to be a useful addition to the drugs available for the treatment of myocardial failure of various causes. It is now being studied in patients with heart failure due to coronary artery disease.", "contents": "Circulatory effects of tazolol in experimental myocardial infarction. The hemodynamic effects of tazolol, a new long-acting beta-stimulating drug, were studied in dogs with acute pump failure caused by experimental myocardial infarction and the results were compared with the actions of isoproterenol given in small and large doses. Tazolol produced a significant and sustained increase in cardiac output and stroke volume, while causing a decrease in peripheral resistance and mean aortic pressure. Heart rate was only modestly increased. Compared with isoproterenol at equivalent doses. tazolol appeared to cause less S-T segment elevation at the margin of infarction. The increase in double product (systolic pressure X heart rate) produced by tazolol was also considerably less than that of isoproterenol. Tazolol may prove to be a useful addition to the drugs available for the treatment of myocardial failure of various causes. It is now being studied in patients with heart failure due to coronary artery disease."}
{"id": "PMID:235835", "title": "Double-blind comparison of the effectiveness of azathioprine and sulfasalazine in idiopathic proctocolitis. Preliminary report.", "content": "A double-blind therapeutic trial of azathioprine in 20 patients with acute proctocolitis was performed over a 3-month period. Azathioprine was compared with sulfasalazine in patients paired and treated in a sequential order. Clinical, laboratory, endoscopic, biopsy, and radiologic data were assessed by semiquantitative criteria. No significant difference in the effect of the drugs was observed. Both azathioprine and sulfasalazine produce significant improvement in clinical symptoms, some laboratory findings (ESR, serum iron), and endoscopic and biopsy findings (P smaller than 0.05). Radiologic improvement was less evident (P smaller than 0.10). On the overall final evaluation of the trial, 14 patients were improved, and 6 remained stationary or worsened (P smaller than 0.10). This short-term trial confirms previous uncontrolled experiences of one of the authors on larger series of patients.", "contents": "Double-blind comparison of the effectiveness of azathioprine and sulfasalazine in idiopathic proctocolitis. Preliminary report. A double-blind therapeutic trial of azathioprine in 20 patients with acute proctocolitis was performed over a 3-month period. Azathioprine was compared with sulfasalazine in patients paired and treated in a sequential order. Clinical, laboratory, endoscopic, biopsy, and radiologic data were assessed by semiquantitative criteria. No significant difference in the effect of the drugs was observed. Both azathioprine and sulfasalazine produce significant improvement in clinical symptoms, some laboratory findings (ESR, serum iron), and endoscopic and biopsy findings (P smaller than 0.05). Radiologic improvement was less evident (P smaller than 0.10). On the overall final evaluation of the trial, 14 patients were improved, and 6 remained stationary or worsened (P smaller than 0.10). This short-term trial confirms previous uncontrolled experiences of one of the authors on larger series of patients."}
{"id": "PMID:235836", "title": "Influence of the proximal small intestine on the gastric hypersecretion in pylorus-ligated rats.", "content": "The mechanism of the gastric secretory inhibition caused by the simultaneous ligation of the upper and lower duodenum or the jejunum in pylorus-ligated rats was studied. The data obtained from the experiments on surgical manipulation of the small intestine indicated that the absorption of certain substances appeared to be important in maintaining gastric secretion of pylorus-ligated rats. The participation of biliary secretion was negligible, while the ligation procedure per se, which results in the accumulation of duodenal contents, might be partly involved in the mechanism of acid secretion. Pharmacological techniques suggested that the inhibition appeared to be independent of cholinergic nervous reflex and hormonal influence, which is assumed to be released by intestinal acidification.", "contents": "Influence of the proximal small intestine on the gastric hypersecretion in pylorus-ligated rats. The mechanism of the gastric secretory inhibition caused by the simultaneous ligation of the upper and lower duodenum or the jejunum in pylorus-ligated rats was studied. The data obtained from the experiments on surgical manipulation of the small intestine indicated that the absorption of certain substances appeared to be important in maintaining gastric secretion of pylorus-ligated rats. The participation of biliary secretion was negligible, while the ligation procedure per se, which results in the accumulation of duodenal contents, might be partly involved in the mechanism of acid secretion. Pharmacological techniques suggested that the inhibition appeared to be independent of cholinergic nervous reflex and hormonal influence, which is assumed to be released by intestinal acidification."}
{"id": "PMID:235837", "title": "Inhibitory effect of bromazepam on insulin-stimulated gastric acid secretion in man.", "content": "The action of bromazepam on insulin-stimulated gastric acid secretion was examined in 5 healthy volunteers in a randomized study. To measure acid output, the intragastric titration technique and a pH-sensitive telemetering capsule were used. Three series of experiments were performed: (1) insulin (0.2 U/kg body weight), stimulation alone; (2) simultaneous injection of insulin and bromazepam (0.1 mg/kg body weight), subjects kept awake; (3) synchronous injection of insulin and bromazepam but with subjects allowed to fall asleep after drug administration. In all three series after insulin administration a significant initial inhibition of gastric secretion occurred. There were no significant differences between the three series regarding the intensity of hypoglycemia. Blood glucose levels lower than 25 mg/100 ml were reached in all experiments. Bromazepam in subjects kept awake caused drowsiness and a lower gastric acid response to hypoglycemia as compared to insulin alone, but the difference was not significant. In subjects allowed to sleep, this reduction was marked and gastric acid output was significantly lower than in both other series. These findings suggest that sleep and drowsiness, rather than bromazepam itself, cause inhibition of insulin-induced gastric secretion.", "contents": "Inhibitory effect of bromazepam on insulin-stimulated gastric acid secretion in man. The action of bromazepam on insulin-stimulated gastric acid secretion was examined in 5 healthy volunteers in a randomized study. To measure acid output, the intragastric titration technique and a pH-sensitive telemetering capsule were used. Three series of experiments were performed: (1) insulin (0.2 U/kg body weight), stimulation alone; (2) simultaneous injection of insulin and bromazepam (0.1 mg/kg body weight), subjects kept awake; (3) synchronous injection of insulin and bromazepam but with subjects allowed to fall asleep after drug administration. In all three series after insulin administration a significant initial inhibition of gastric secretion occurred. There were no significant differences between the three series regarding the intensity of hypoglycemia. Blood glucose levels lower than 25 mg/100 ml were reached in all experiments. Bromazepam in subjects kept awake caused drowsiness and a lower gastric acid response to hypoglycemia as compared to insulin alone, but the difference was not significant. In subjects allowed to sleep, this reduction was marked and gastric acid output was significantly lower than in both other series. These findings suggest that sleep and drowsiness, rather than bromazepam itself, cause inhibition of insulin-induced gastric secretion."}
{"id": "PMID:235838", "title": "Ecologic studies of Venezuelan encephalitis virus in Peru during 1970-1971.", "content": "Venezuelan encephalitis (VE) virus has intermittently produced epidemics and equine epizootics on the dry Pacific coastal plain of Peru since at least the 1930's. However, evidence that the virus exists in the Amazon region of Peru to the east of the Andes mountains was not obtained until antibodies were found in human sera collected in 1965, and 10 strains of the virus were isolated in a forest near the city of Iquitos, Peru during February and March 1971. Eight strains came from mosquitoes and two from dead sentinel hamsters. Three hamsters exposed in forests near Iquitos developed VE virus antibodies suggesting that hamster-benign strains also exist there. Antibody tests of equine sera revealed no evidence that VE virus was actively cycling during the late 1950's or 1960's in southern coastal Peru, where equine epizootics had occurred in the 1930's and 1940's. In northern coastal Peru bordering Ecuador, antibodies were present in equine sera, presumably residual from the 1969 outbreak caused by subtype I virus, since neutralizing antibody titers were higher to subtype I virus than to subtypes III or IV. No VE virus was detected in this northern region during the dry season of 1970 by use of sentinel hamsters. The possibility is considered that VE epidemics and equine epizootics on the Pacific coast of Peru are caused by movements of virus in infected vertebrates traversing Andean passes or in infected vertebrates or mosquitoes carried in airplanes from the Amazon region.", "contents": "Ecologic studies of Venezuelan encephalitis virus in Peru during 1970-1971. Venezuelan encephalitis (VE) virus has intermittently produced epidemics and equine epizootics on the dry Pacific coastal plain of Peru since at least the 1930's. However, evidence that the virus exists in the Amazon region of Peru to the east of the Andes mountains was not obtained until antibodies were found in human sera collected in 1965, and 10 strains of the virus were isolated in a forest near the city of Iquitos, Peru during February and March 1971. Eight strains came from mosquitoes and two from dead sentinel hamsters. Three hamsters exposed in forests near Iquitos developed VE virus antibodies suggesting that hamster-benign strains also exist there. Antibody tests of equine sera revealed no evidence that VE virus was actively cycling during the late 1950's or 1960's in southern coastal Peru, where equine epizootics had occurred in the 1930's and 1940's. In northern coastal Peru bordering Ecuador, antibodies were present in equine sera, presumably residual from the 1969 outbreak caused by subtype I virus, since neutralizing antibody titers were higher to subtype I virus than to subtypes III or IV. No VE virus was detected in this northern region during the dry season of 1970 by use of sentinel hamsters. The possibility is considered that VE epidemics and equine epizootics on the Pacific coast of Peru are caused by movements of virus in infected vertebrates traversing Andean passes or in infected vertebrates or mosquitoes carried in airplanes from the Amazon region."}
{"id": "PMID:235839", "title": "Antigenic and biologic characteristics of Venezuelan encephalitis virus strains including a possible new subtype, isolated from the Amazon region of Peru in 1971.", "content": "Nine strains of Venezuelan encephalitis (VE) virus isolated from the Amazon region of Peru in 1971 were identified as antigenic subtype I based on plaque-reduction neutralization tests with four and 20 units of antibody. A tenth strain, 71D1252, was possibly a new subtype, but was related to subtypes I and III. Hemagglutinins of each strain made from infected mouse brains had optimals pHs of 6.2 and 6.4. Nine strains were pathogenic for adult hamsters and adult mice, but strain 71D1252 inapparently infected some adult hamsters and mice inoculated peripherally. Plaques of nine strains in Vero African green monkey kidney cell cultures were intermediate in size between representative epizootic and enzootic strains, but plaques of strain 71D1252 were small like epizootic strains.", "contents": "Antigenic and biologic characteristics of Venezuelan encephalitis virus strains including a possible new subtype, isolated from the Amazon region of Peru in 1971. Nine strains of Venezuelan encephalitis (VE) virus isolated from the Amazon region of Peru in 1971 were identified as antigenic subtype I based on plaque-reduction neutralization tests with four and 20 units of antibody. A tenth strain, 71D1252, was possibly a new subtype, but was related to subtypes I and III. Hemagglutinins of each strain made from infected mouse brains had optimals pHs of 6.2 and 6.4. Nine strains were pathogenic for adult hamsters and adult mice, but strain 71D1252 inapparently infected some adult hamsters and mice inoculated peripherally. Plaques of nine strains in Vero African green monkey kidney cell cultures were intermediate in size between representative epizootic and enzootic strains, but plaques of strain 71D1252 were small like epizootic strains."}
{"id": "PMID:235840", "title": "Effect of briefly heating cyclophosphamide solutions.", "content": "Solutions containing cyclophosphamide monohydrate were heated to 50 C, 60 C, 70 C and 80 C for 15 minutes and then assayed for potency. Solutions heated to 50 Cor 60 C did not change appreciably; those heated to 70 C and 80 C assayed at 90.2% and 77.5%, respectively, of initial potency. The values compared well with those calculated using the Arrhenius equation. It is concluded that warming vials of cyclophosphamide monohydrate after adding an aqueous vehicle (in order to achieve rapid dissolution) could decrease the potency of the final injectable product.", "contents": "Effect of briefly heating cyclophosphamide solutions. Solutions containing cyclophosphamide monohydrate were heated to 50 C, 60 C, 70 C and 80 C for 15 minutes and then assayed for potency. Solutions heated to 50 Cor 60 C did not change appreciably; those heated to 70 C and 80 C assayed at 90.2% and 77.5%, respectively, of initial potency. The values compared well with those calculated using the Arrhenius equation. It is concluded that warming vials of cyclophosphamide monohydrate after adding an aqueous vehicle (in order to achieve rapid dissolution) could decrease the potency of the final injectable product."}
{"id": "PMID:235841", "title": "Current therapy of hypertension. A pharmacologic approach.", "content": "Adequate treatment of hypertension requires that the physician understand the pharmacologic actions of antihypertensive agents. Although no drug is without adverse reactions, it should be possible to choose an agent or combination of agents which can effectively lower blood pressure and be tolerated by the patient. The indications, proposed mechanisms of actions and adverse effects of the following antihypertensive drugs are discussed: thiazide diuretics, spironolactone, triamterene, trimethaphan, Rauwolfia alkaloids. guanethidine, bethanidine, methyldopa, clonidine, pargyline, propranolol, hydrazaline, minoxidil, guancydine, diazoxide and sodium nitroprusside.", "contents": "Current therapy of hypertension. A pharmacologic approach. Adequate treatment of hypertension requires that the physician understand the pharmacologic actions of antihypertensive agents. Although no drug is without adverse reactions, it should be possible to choose an agent or combination of agents which can effectively lower blood pressure and be tolerated by the patient. The indications, proposed mechanisms of actions and adverse effects of the following antihypertensive drugs are discussed: thiazide diuretics, spironolactone, triamterene, trimethaphan, Rauwolfia alkaloids. guanethidine, bethanidine, methyldopa, clonidine, pargyline, propranolol, hydrazaline, minoxidil, guancydine, diazoxide and sodium nitroprusside."}
{"id": "PMID:235842", "title": "Adverse reactions and interactions limiting the use of antihypertensive drugs.", "content": "One major problem in the management of hypertensive patients is their lack of compliance with therapeutic regimens. Some of the problem with compliance is due to side effects of the drugs being used. Additionally, drug resistance may be related to interactions of antihypertensive drugs with other prescription and nonprescription drugs. By classifying drugs into common modes of action, common side effects can be predicted. However, each drug has its own spectrum of other side effects which can be dose-limiting. Most of the side effects are extensions of the pharmacologic actions of these drugs, and only relatively rarely is an allergic reaction a problem. Drug interactions can be important in explaining some side effects or drug resistance. A knowledge of the pharmacology of the antihypertensive drugs allows the physician to predict, in many cases, the possibility of an interaction and, indeed, can allow the use of interactions to advantage as with combinations of vasodilators and beta adrenergic blocking drugs. Until such time as the perfect antihypertensive drug is discovered, most patients can be managed satisfactorily with minimal side effects by judicious combination of available drugs and avoiding drugs which interact to cause more side effects or decrease the antihypertensive effects.", "contents": "Adverse reactions and interactions limiting the use of antihypertensive drugs. One major problem in the management of hypertensive patients is their lack of compliance with therapeutic regimens. Some of the problem with compliance is due to side effects of the drugs being used. Additionally, drug resistance may be related to interactions of antihypertensive drugs with other prescription and nonprescription drugs. By classifying drugs into common modes of action, common side effects can be predicted. However, each drug has its own spectrum of other side effects which can be dose-limiting. Most of the side effects are extensions of the pharmacologic actions of these drugs, and only relatively rarely is an allergic reaction a problem. Drug interactions can be important in explaining some side effects or drug resistance. A knowledge of the pharmacology of the antihypertensive drugs allows the physician to predict, in many cases, the possibility of an interaction and, indeed, can allow the use of interactions to advantage as with combinations of vasodilators and beta adrenergic blocking drugs. Until such time as the perfect antihypertensive drug is discovered, most patients can be managed satisfactorily with minimal side effects by judicious combination of available drugs and avoiding drugs which interact to cause more side effects or decrease the antihypertensive effects."}
{"id": "PMID:235843", "title": "Aqueous humor pH changes after experimental alkali burns.", "content": "Following application of 2N sodium hydroxide, or 8.1N ammonium hydroxide to rabbit cornea, the aqueous humor pH reached a maximum of 10.2, 11.9, and 12 within six minutes following 20-, 50-, and 100-mu1 sodium hydroxide burns, respectively; after two hours the pH had fallen to 8.5, 10, and 10.5. The maximum rise following application of 100-mu1 of ammonium hydroxide was 10.8, declining to about 9 at two hours. The fall in pH following a 100-mu1 sodium hydroxide burn was not greatly influence by external lavage. However, the pH was significantly lowered (12 to 10) by paracentesis alone and further reduced by immediate or delayed intracameral administration of phosphate buffer. On the basis of these results moderately severe and severe alkali burns of the eye should be treated by paracentesis and if possible with anterior chamber reformation with a sterile solution.", "contents": "Aqueous humor pH changes after experimental alkali burns. Following application of 2N sodium hydroxide, or 8.1N ammonium hydroxide to rabbit cornea, the aqueous humor pH reached a maximum of 10.2, 11.9, and 12 within six minutes following 20-, 50-, and 100-mu1 sodium hydroxide burns, respectively; after two hours the pH had fallen to 8.5, 10, and 10.5. The maximum rise following application of 100-mu1 of ammonium hydroxide was 10.8, declining to about 9 at two hours. The fall in pH following a 100-mu1 sodium hydroxide burn was not greatly influence by external lavage. However, the pH was significantly lowered (12 to 10) by paracentesis alone and further reduced by immediate or delayed intracameral administration of phosphate buffer. On the basis of these results moderately severe and severe alkali burns of the eye should be treated by paracentesis and if possible with anterior chamber reformation with a sterile solution."}
{"id": "PMID:235844", "title": "Ophthalmic manifestations of Aarskog (facial-digital-genital) syndrome.", "content": "Four boys with facial-digital-genital or Aarskog syndrome were whort with triangular faces, characteristic deformities of the hands and feet, and anomalies of the external genitalia. The syndrome appears to be inherited in an X-chromosomes-limked recessive manner. Previous reports emphasized the presence of hypertelorism but careful measurements of the interorbital dimensions revealed primary telecanthus in addition to hypertelorism. The palpebral fissures had a marked antimongoloid obliquity and in half the reported cases, there was unilateral or bilateral congenital blepharoptosis. Strabismus, hyperopic astigmatism, and large corneas may be additional features.", "contents": "Ophthalmic manifestations of Aarskog (facial-digital-genital) syndrome. Four boys with facial-digital-genital or Aarskog syndrome were whort with triangular faces, characteristic deformities of the hands and feet, and anomalies of the external genitalia. The syndrome appears to be inherited in an X-chromosomes-limked recessive manner. Previous reports emphasized the presence of hypertelorism but careful measurements of the interorbital dimensions revealed primary telecanthus in addition to hypertelorism. The palpebral fissures had a marked antimongoloid obliquity and in half the reported cases, there was unilateral or bilateral congenital blepharoptosis. Strabismus, hyperopic astigmatism, and large corneas may be additional features."}
{"id": "PMID:235847", "title": "Steady-state glucose oxidation by dog kidney in vivo: relation to Na+ reabsorption.", "content": "In eight experiments at normal or slightly elevated blood glucose concentration we quantified the steady-state renal glucose oxidation rate (see article) during control, at reduced Naomega absorptive rates (raised ureteral pressure), and during respiratory alkalosis. A tracer amount of either [1-14C]glucose or or [U-14C]D(omega)-glucose was infused at a constant rate into one renal artery. (see article) was calculated from the renal 14CO2 production rate (corrected for recirculation) and the specific activity of glucose in renal arterial blood. The control (see article) (n equals 8) equals 4.40 plus or minus 0.9 mumol/100 g-min (mean plus or minus SE). When net Naomega reabsorption was decreased by 45% (n equals 6), or when the pH of extracellular fluid was raised (n equals 2), no significant effect on (see article) (9.1 plus or minus 4.2 and 3.9 plus or minus 2.3 mumol/min-100 g, respectively) occurred. The mean glucose oxidation rate for all experiments was 5.65 plus or minus 1.73 mumol g-1-min-1 and required similar to 13% of the renal O2 utilization. Glucose oxidation provides energy either for basal renal work or for some portion of renal transport work not affected by increased ureteral pressure.", "contents": "Steady-state glucose oxidation by dog kidney in vivo: relation to Na+ reabsorption. In eight experiments at normal or slightly elevated blood glucose concentration we quantified the steady-state renal glucose oxidation rate (see article) during control, at reduced Naomega absorptive rates (raised ureteral pressure), and during respiratory alkalosis. A tracer amount of either [1-14C]glucose or or [U-14C]D(omega)-glucose was infused at a constant rate into one renal artery. (see article) was calculated from the renal 14CO2 production rate (corrected for recirculation) and the specific activity of glucose in renal arterial blood. The control (see article) (n equals 8) equals 4.40 plus or minus 0.9 mumol/100 g-min (mean plus or minus SE). When net Naomega reabsorption was decreased by 45% (n equals 6), or when the pH of extracellular fluid was raised (n equals 2), no significant effect on (see article) (9.1 plus or minus 4.2 and 3.9 plus or minus 2.3 mumol/min-100 g, respectively) occurred. The mean glucose oxidation rate for all experiments was 5.65 plus or minus 1.73 mumol g-1-min-1 and required similar to 13% of the renal O2 utilization. Glucose oxidation provides energy either for basal renal work or for some portion of renal transport work not affected by increased ureteral pressure."}
{"id": "PMID:235848", "title": "Neuroleptics, catecholamines, and psychoses: a study of their interrelations.", "content": "The authors examined central catecholamine metabolism in various symptomatological psychotic disorders and the relationship between the biochemical and therapeutic action profiles of neuroleptics. Haloperidol and (to a lesser entent) chlorpromaziner icrease the dopamine (DA) turnover in the central nervous system, but the authors influenced; oxypertine has the reverse effect. The authors question whether disorders of DA-metabolism underlie or result from disorders of motor activity, postulating that the hyperdopaminergic activity observable in psychoses is dependent on motor hyperactivity rather than on \"true\" or psychotic symptoms such as delusions and hallucinations.", "contents": "Neuroleptics, catecholamines, and psychoses: a study of their interrelations. The authors examined central catecholamine metabolism in various symptomatological psychotic disorders and the relationship between the biochemical and therapeutic action profiles of neuroleptics. Haloperidol and (to a lesser entent) chlorpromaziner icrease the dopamine (DA) turnover in the central nervous system, but the authors influenced; oxypertine has the reverse effect. The authors question whether disorders of DA-metabolism underlie or result from disorders of motor activity, postulating that the hyperdopaminergic activity observable in psychoses is dependent on motor hyperactivity rather than on \"true\" or psychotic symptoms such as delusions and hallucinations."}
{"id": "PMID:235849", "title": "MMPI delineation of a subgroup of depressed patients refractory to lithium carbonate therapy.", "content": "The authors found that in a sample of 26 severely depressed hospitalized patients, 5 patients with low depression and psychasthenia profiles on the Minnesota Multiphasic Personality Inventory did not show an antidepressant response to lithium carbonate. Seventeen of 21 depressed patients with high depression and psychasthenia profiles did  respond to the antidepressant effects of the drug. They tentatively conclue that by using the MMPI it is possible to delineate a subgroup of depressed patients who are refractory to lithium carbonate therapy.", "contents": "MMPI delineation of a subgroup of depressed patients refractory to lithium carbonate therapy. The authors found that in a sample of 26 severely depressed hospitalized patients, 5 patients with low depression and psychasthenia profiles on the Minnesota Multiphasic Personality Inventory did not show an antidepressant response to lithium carbonate. Seventeen of 21 depressed patients with high depression and psychasthenia profiles did  respond to the antidepressant effects of the drug. They tentatively conclue that by using the MMPI it is possible to delineate a subgroup of depressed patients who are refractory to lithium carbonate therapy."}
{"id": "PMID:235851", "title": "[Blood gas studies on the efficiency of the ventilator \"Pulmomat\" (author's transl)].", "content": "Efficiency of ventilation of Pulmomat has been examined in 48 patients under general anaesthesia and relaxation during normoventilation and hyperventilation of 15 and 30% degree. For criteria the acid-base status of arterial blood has been used. In normoventilation acid-base status remained unchanged within the normal range providing a regular control respectively correction of ventilationvolumes. There was no significant difference between results of 15 and 30% hyperventilation. In both situations arterial pCO-2 was reduced 15-20%. There was a tendency to acidosis in all kinds of ventilation presumably as a consequence of surgical effects. For security using the Pulmomat as respirator, a hyperventilation of 15% degree is recommanded in clinical use.", "contents": "[Blood gas studies on the efficiency of the ventilator \"Pulmomat\" (author's transl)]. Efficiency of ventilation of Pulmomat has been examined in 48 patients under general anaesthesia and relaxation during normoventilation and hyperventilation of 15 and 30% degree. For criteria the acid-base status of arterial blood has been used. In normoventilation acid-base status remained unchanged within the normal range providing a regular control respectively correction of ventilationvolumes. There was no significant difference between results of 15 and 30% hyperventilation. In both situations arterial pCO-2 was reduced 15-20%. There was a tendency to acidosis in all kinds of ventilation presumably as a consequence of surgical effects. For security using the Pulmomat as respirator, a hyperventilation of 15% degree is recommanded in clinical use."}
{"id": "PMID:235852", "title": "[PO-2-PCO-2-pH-nomograms for rat blood at 37 degrees C (author's transl)].", "content": "In order to determine the interdependence of the parameters of the respiratory gas transport in rat blood (Sprague-Dawley) CO-2-equilibration curves in fully oxygenated and deoxygenated blood are measured. The results are presented in the form of pH-log P-CO-2-diagrams. O-2-dissociation curves of rat blood are registered at different CO-2 partial pressures. The P-02 at S-02 equals 50% ranged between 27.7 mm Hg for P-C0-2 equals 20 mm Hg. 35.1 mm Hg for P-C0-2 equals 40 mm Hg and 42.2 for P-C0-2 equals 60 mm Hg. Cartesian and alignment nomograms are constructed using CO-2 equilibration curves and O-2 dissociation curves. These nomograms give the interrelations between P-O-2, P-CO-2, pH and S-0-2 of rat blood. Separate nomograms are presented for Hb-concentrations of 10-13 g-% and 13.1-16 g-% because of great variations of Hb concentration in rat blood. If two of these values are known the nomograms permit the reading of the remaining paramters.", "contents": "[PO-2-PCO-2-pH-nomograms for rat blood at 37 degrees C (author's transl)]. In order to determine the interdependence of the parameters of the respiratory gas transport in rat blood (Sprague-Dawley) CO-2-equilibration curves in fully oxygenated and deoxygenated blood are measured. The results are presented in the form of pH-log P-CO-2-diagrams. O-2-dissociation curves of rat blood are registered at different CO-2 partial pressures. The P-02 at S-02 equals 50% ranged between 27.7 mm Hg for P-C0-2 equals 20 mm Hg. 35.1 mm Hg for P-C0-2 equals 40 mm Hg and 42.2 for P-C0-2 equals 60 mm Hg. Cartesian and alignment nomograms are constructed using CO-2 equilibration curves and O-2 dissociation curves. These nomograms give the interrelations between P-O-2, P-CO-2, pH and S-0-2 of rat blood. Separate nomograms are presented for Hb-concentrations of 10-13 g-% and 13.1-16 g-% because of great variations of Hb concentration in rat blood. If two of these values are known the nomograms permit the reading of the remaining paramters."}
{"id": "PMID:235864", "title": "Neurohumoral mechanisms in hypertension.", "content": "Neurohumoral mechanisms operating via the catecholamines are discussed in their relationship to such hypertensive diseases as pheochromocytoma and labile and established essential hypertension. 2. In pheochromocytoma, diagnosis depends almost entirely on identification of increased amounts of catecholamine metabolites in the urine. Because of the danger, manipulative or invasive procedures both for diagnosis and during surgery should be kept at a minimum. 3. In established essential hypertension, reactivity to norepinephrine and plasma norepinephrine are increased, whereas norepinephrine uptake and apparent secretion rate are decreased. 4. In labile essential hypertension, reactivity to epinephrine and probably plasma epinephrine are increased and uptake of epinephrine decreased. 5. Labile hypertension with all its characteristics may or may not coexist with established  essential hypertension with all its features. 6. The sympathetic nervous system is also involved in other types of hypertensive disease. Many patients with renovascular hypertension as well as with primary and secondary hyperaldosteronism also have essential hypertension. Angiotensin II affects the sympathetic nervous system and the juxtaglomerular apparatus appears to be beta adrenergic receptor activated, at least in part.", "contents": "Neurohumoral mechanisms in hypertension. Neurohumoral mechanisms operating via the catecholamines are discussed in their relationship to such hypertensive diseases as pheochromocytoma and labile and established essential hypertension. 2. In pheochromocytoma, diagnosis depends almost entirely on identification of increased amounts of catecholamine metabolites in the urine. Because of the danger, manipulative or invasive procedures both for diagnosis and during surgery should be kept at a minimum. 3. In established essential hypertension, reactivity to norepinephrine and plasma norepinephrine are increased, whereas norepinephrine uptake and apparent secretion rate are decreased. 4. In labile essential hypertension, reactivity to epinephrine and probably plasma epinephrine are increased and uptake of epinephrine decreased. 5. Labile hypertension with all its characteristics may or may not coexist with established  essential hypertension with all its features. 6. The sympathetic nervous system is also involved in other types of hypertensive disease. Many patients with renovascular hypertension as well as with primary and secondary hyperaldosteronism also have essential hypertension. Angiotensin II affects the sympathetic nervous system and the juxtaglomerular apparatus appears to be beta adrenergic receptor activated, at least in part."}
{"id": "PMID:235861", "title": "Arterial blood-gas analyses during electroconvulsive therapy in a parturient.", "content": "Arterial blood gases and vital signs were monitored in a patient receiving electroconvulsive therapy (ECT) during the third trimester of pregnancy. Alterations in blood pressure and heart rate were similar to those noted in prior studies. Pretreating with 100 percent oxygen (02) and assisting ventilation until return of adequate spontaneous respirations, prevented hypoxemia, significant hypercarbia, and cardiovascular changes. The administration of succinylcholine prevented the systemic manifestations of the electrically-induced seizure. One fetal arrhythmia occurred, apparently unrelated to changes in maternal Pa02, and resolved spontaneously. This technic of anesthesia would appear to be acceptable for ECT in the parturient.", "contents": "Arterial blood-gas analyses during electroconvulsive therapy in a parturient. Arterial blood gases and vital signs were monitored in a patient receiving electroconvulsive therapy (ECT) during the third trimester of pregnancy. Alterations in blood pressure and heart rate were similar to those noted in prior studies. Pretreating with 100 percent oxygen (02) and assisting ventilation until return of adequate spontaneous respirations, prevented hypoxemia, significant hypercarbia, and cardiovascular changes. The administration of succinylcholine prevented the systemic manifestations of the electrically-induced seizure. One fetal arrhythmia occurred, apparently unrelated to changes in maternal Pa02, and resolved spontaneously. This technic of anesthesia would appear to be acceptable for ECT in the parturient."}
{"id": "PMID:235862", "title": "A neurochemical hypothesis for halothane anesthesia.", "content": "We hypothesize that anesthetic agents exert their effects through an inhibition of oxidation of reduced nicotinamide adenine dinucleotide (NADH) in the synaptic regions of the brain. This inhibition could lead to gamma-amino-butyric acid (GABA) accumulation in the synaptic cleft and to hyperpolarization of the post-synaptic membrane. The resulting reduction in synaptic transmission then would manifest itself as the anesthetic state, reducing the work performed by the brain so that cerebral respiration is reduced and cerebral metabolite energy is conserved.", "contents": "A neurochemical hypothesis for halothane anesthesia. We hypothesize that anesthetic agents exert their effects through an inhibition of oxidation of reduced nicotinamide adenine dinucleotide (NADH) in the synaptic regions of the brain. This inhibition could lead to gamma-amino-butyric acid (GABA) accumulation in the synaptic cleft and to hyperpolarization of the post-synaptic membrane. The resulting reduction in synaptic transmission then would manifest itself as the anesthetic state, reducing the work performed by the brain so that cerebral respiration is reduced and cerebral metabolite energy is conserved."}
{"id": "PMID:235860", "title": "Reassessment of the assumed A-V oxygen content difference in the shunt calculation.", "content": "A study was undertaken in 15 patients to compare measured and assumed arteriovenous oxygen (A-V O2) content differences and their effects on resultant shunt calculations. All patients were on volume ventilators and demonstrated a stable cardiovascular state. Simultaneous measurements of the O2 content of a pulmonary artery (PA) and of a superior vena cava (SVC) sample were compared. A mean A-V 02 content difference of 3.5 plus or minus 0.8 volumes percent was obtained from the PA and 2.6 plus or minus 1.1 volumes percent from the SVC. The resultant shunt calculations derived from measured A-V 02 content differences were compared with the calculation based on an assumed A-V O2 content difference of 5 volumes percent. A method for extrapolating a \"true\" A-V 02 content difference from an SVC blood sample was obtained. The extrapolated value resulted in a more representative \"true shunt\" calculation in 13 of the 15 patients.", "contents": "Reassessment of the assumed A-V oxygen content difference in the shunt calculation. A study was undertaken in 15 patients to compare measured and assumed arteriovenous oxygen (A-V O2) content differences and their effects on resultant shunt calculations. All patients were on volume ventilators and demonstrated a stable cardiovascular state. Simultaneous measurements of the O2 content of a pulmonary artery (PA) and of a superior vena cava (SVC) sample were compared. A mean A-V 02 content difference of 3.5 plus or minus 0.8 volumes percent was obtained from the PA and 2.6 plus or minus 1.1 volumes percent from the SVC. The resultant shunt calculations derived from measured A-V 02 content differences were compared with the calculation based on an assumed A-V O2 content difference of 5 volumes percent. A method for extrapolating a \"true\" A-V 02 content difference from an SVC blood sample was obtained. The extrapolated value resulted in a more representative \"true shunt\" calculation in 13 of the 15 patients."}
{"id": "PMID:235868", "title": "Duck viral enteritis (duck plague) characteristics and immune response of the host.", "content": "Duck viral enteritis (DVE) is caused by a herpesvirus whose biologic and physical characteristics are similar to those described for the group of herpesviruses. Only one immunologic and serologic type is known. A low level of neutralizing antibodies is developed in waterfowl vaccinated with the chicken embryo attenuated DVE virus. A marked anamnestic serologic response resulted from challenge with virulent virus. Waterfowl resisting exposure with virulent virus were solidly immune. However, waterfowl which possessed moderate level of neutralizing antibodies succumbed when their immunity was challenged with virulent virus when secondary or latent microbial invaders were present. This may partially explain the lack of correlation between the levels of neutralizing antibodies and mortality from infection with DVE virulent virus.", "contents": "Duck viral enteritis (duck plague) characteristics and immune response of the host. Duck viral enteritis (DVE) is caused by a herpesvirus whose biologic and physical characteristics are similar to those described for the group of herpesviruses. Only one immunologic and serologic type is known. A low level of neutralizing antibodies is developed in waterfowl vaccinated with the chicken embryo attenuated DVE virus. A marked anamnestic serologic response resulted from challenge with virulent virus. Waterfowl resisting exposure with virulent virus were solidly immune. However, waterfowl which possessed moderate level of neutralizing antibodies succumbed when their immunity was challenged with virulent virus when secondary or latent microbial invaders were present. This may partially explain the lack of correlation between the levels of neutralizing antibodies and mortality from infection with DVE virulent virus."}
{"id": "PMID:235869", "title": "Pulmonary function in asymptomatic adolescents with idiopathic scoliosis.", "content": "Pulmonary function studies were performed in 28 asymptomatic adolescents with idiopathic scoliosis. Tests included spirometry, flow volume curve, measurements of inspired gas distribution, diffusing capacity, closing volume, ventilatory response to carbon dioxide, and arterial blood gas analysis. In addition to the well-known decreases in lung volumes, a reduction in diffusing capacity, arterial oxygen tension, and ventilatory response to carbon dioxide were also documented. Significant correlations existed between the severity of the spinal curvature and the decrease in lung volumes. A significant correlation was also found between the degree of hypoxemia and the reduction in the diffusing capacity, suggesting that a low diffusing could be the cause of the observed arterial hypoxemia.", "contents": "Pulmonary function in asymptomatic adolescents with idiopathic scoliosis. Pulmonary function studies were performed in 28 asymptomatic adolescents with idiopathic scoliosis. Tests included spirometry, flow volume curve, measurements of inspired gas distribution, diffusing capacity, closing volume, ventilatory response to carbon dioxide, and arterial blood gas analysis. In addition to the well-known decreases in lung volumes, a reduction in diffusing capacity, arterial oxygen tension, and ventilatory response to carbon dioxide were also documented. Significant correlations existed between the severity of the spinal curvature and the decrease in lung volumes. A significant correlation was also found between the degree of hypoxemia and the reduction in the diffusing capacity, suggesting that a low diffusing could be the cause of the observed arterial hypoxemia."}
{"id": "PMID:235871", "title": "Stress ulceration and the gastric mucosal barrier.", "content": "The role of the gastric mucosal barrier in the pathogenesis of post-traumatic stress ulcerations is far from clear. Clinical studies on critically ill patients have shown disrupted gastric mucosal barriers with hydrogen ion back diffusion, but no correlation has been made between these findings and gastric erosions. In addition, numerous assumptions concerning gastric secretions, pyloric loss and esophageal contributions to the assayed gastric juice have to be made in these patients. There is contradictory experimental evidence concerning the theory that gastric mucosal ischemia or hypotension disrupts the normal gastric mucosal barrier. In subhuman primate studies, there is no increased back diffusion acid during hypotension or during the reinfusion periods. Even though there may not be increased permeability to H+, the presence of acid is a requirement for the development of stress ulcerations. The role of agents such as bile salts and aspirin is clearer. If these agents are present, increased back diffusion of acid is likely, but its role in the pathophysiology of post-traumatic gastric erosion awaits further clarification.", "contents": "Stress ulceration and the gastric mucosal barrier. The role of the gastric mucosal barrier in the pathogenesis of post-traumatic stress ulcerations is far from clear. Clinical studies on critically ill patients have shown disrupted gastric mucosal barriers with hydrogen ion back diffusion, but no correlation has been made between these findings and gastric erosions. In addition, numerous assumptions concerning gastric secretions, pyloric loss and esophageal contributions to the assayed gastric juice have to be made in these patients. There is contradictory experimental evidence concerning the theory that gastric mucosal ischemia or hypotension disrupts the normal gastric mucosal barrier. In subhuman primate studies, there is no increased back diffusion acid during hypotension or during the reinfusion periods. Even though there may not be increased permeability to H+, the presence of acid is a requirement for the development of stress ulcerations. The role of agents such as bile salts and aspirin is clearer. If these agents are present, increased back diffusion of acid is likely, but its role in the pathophysiology of post-traumatic gastric erosion awaits further clarification."}
{"id": "PMID:235872", "title": "Total coronary blood flow measurements and myocardial metabolism during cardiopulmonary bypass in a canine model.", "content": "Myocardial respiratory function and total coronary blood flow were evaluated during cardiopulmonary bypass in 18 dogs. The fibrillating heart was found to be associated with an increase in myocardial oxygen utilization and metabolic rate which was compensated for by a corresponding increase in total coronary blood flow. Following anoxic arrest of the heart, there appears to be an initial impairment to oxygen utilization. Oxygen consumption does not return to normal after 15 minutes of restoring coronary blood flow. The stability of the experimental model as outlined in this study is thought to be related to the use of autologous blood in priming the extracorporeal circuit.", "contents": "Total coronary blood flow measurements and myocardial metabolism during cardiopulmonary bypass in a canine model. Myocardial respiratory function and total coronary blood flow were evaluated during cardiopulmonary bypass in 18 dogs. The fibrillating heart was found to be associated with an increase in myocardial oxygen utilization and metabolic rate which was compensated for by a corresponding increase in total coronary blood flow. Following anoxic arrest of the heart, there appears to be an initial impairment to oxygen utilization. Oxygen consumption does not return to normal after 15 minutes of restoring coronary blood flow. The stability of the experimental model as outlined in this study is thought to be related to the use of autologous blood in priming the extracorporeal circuit."}
{"id": "PMID:235874", "title": "Ocular penetration of pilocarpine: the effect of pH on the ocular penetration of pilocarpine.", "content": "Under the conditions of this study, tritiated pilocarpine was topically applied to rabbits, and the activity in the aqueous humor was measured at selected times. It was found that higher pH affords greater pilocarpine penetration. At pH 7.5, for example, penetration into the aqueous was twice as great as at pH 4.", "contents": "Ocular penetration of pilocarpine: the effect of pH on the ocular penetration of pilocarpine. Under the conditions of this study, tritiated pilocarpine was topically applied to rabbits, and the activity in the aqueous humor was measured at selected times. It was found that higher pH affords greater pilocarpine penetration. At pH 7.5, for example, penetration into the aqueous was twice as great as at pH 4."}
{"id": "PMID:235875", "title": "Gas tension and pH in middle ear effusion.", "content": "The composition of gases and the gas tension in middle ear effusion in patients with serous otitis media have been investigated. By using a specially designed micro-method, very small amounts of middle ear fluid could be analyzed. The effusion was obtained by puncturing the air cells of the mastoid process. The average value of P-O2 was 41 mm Hg; Pco2 was 58 mm Hg, pH 7.24. The possible mechanism for the impaired perfusion of the mucous membranes is discussed as well as some clinical consequences.", "contents": "Gas tension and pH in middle ear effusion. The composition of gases and the gas tension in middle ear effusion in patients with serous otitis media have been investigated. By using a specially designed micro-method, very small amounts of middle ear fluid could be analyzed. The effusion was obtained by puncturing the air cells of the mastoid process. The average value of P-O2 was 41 mm Hg; Pco2 was 58 mm Hg, pH 7.24. The possible mechanism for the impaired perfusion of the mucous membranes is discussed as well as some clinical consequences."}
{"id": "PMID:235881", "title": "[Study of oxytetracycline solubility in an aqueous medium].", "content": "Solubility of oxytetracycline dihydrate in aqueous media was studied. It was shown that solubility of the drug in bidistillate at a temperature of 20 degrees was 195 gamma/ml, which was much lower than the requirements of some pharmacopoeia with respect to the drug solubility. Dependence of oxytetracycline dihydrate solubility in the aqueous medium on the values of pH and temperature was found. Indigency of the procedure described in the literature for determination of antibiotic solubility according to the dry weight of the filtrate on addition of large excesses of the solid phase to the system was shown.", "contents": "[Study of oxytetracycline solubility in an aqueous medium]. Solubility of oxytetracycline dihydrate in aqueous media was studied. It was shown that solubility of the drug in bidistillate at a temperature of 20 degrees was 195 gamma/ml, which was much lower than the requirements of some pharmacopoeia with respect to the drug solubility. Dependence of oxytetracycline dihydrate solubility in the aqueous medium on the values of pH and temperature was found. Indigency of the procedure described in the literature for determination of antibiotic solubility according to the dry weight of the filtrate on addition of large excesses of the solid phase to the system was shown."}
{"id": "PMID:235882", "title": "Molecular construction of Clostridium botulinum type F progenitor toxin.", "content": "Molecular dissociation of purified type F progenitor toxin with an S20,W of 10.3 and a molecular weight of 235,000 into two components, toxic and atoxic, was demonstrated by ultracentrifugation, gel filtration, and diethylaminoethyl-Sephadex chromatography at pH 7.5. The ultracentrifugal analysis indicated that type F progenitor toxin dissociates into components of the same molecular size of 5.9S. The toxic component contained a toxicity of 2.5 times 10-8 50% lethal doses per mg of N. Much higher stability of progenitor toxin than that of derivative toxin, particularly at pH below 5, suggests that only progenitor toxin can act as an oral toxin.", "contents": "Molecular construction of Clostridium botulinum type F progenitor toxin. Molecular dissociation of purified type F progenitor toxin with an S20,W of 10.3 and a molecular weight of 235,000 into two components, toxic and atoxic, was demonstrated by ultracentrifugation, gel filtration, and diethylaminoethyl-Sephadex chromatography at pH 7.5. The ultracentrifugal analysis indicated that type F progenitor toxin dissociates into components of the same molecular size of 5.9S. The toxic component contained a toxicity of 2.5 times 10-8 50% lethal doses per mg of N. Much higher stability of progenitor toxin than that of derivative toxin, particularly at pH below 5, suggests that only progenitor toxin can act as an oral toxin."}
{"id": "PMID:235883", "title": "Rhythmic changes in dry heat resistance of Bacillus subtilis spores after rapid changes in pH.", "content": "Heat resistance of freeze-dried Bacillus subtilis spores varied in a rhythmic manner as a function of time between acidification to about pH 1.5 and freezing. A comparable rapid shift to pH 11 produced little change in resistance to heat.", "contents": "Rhythmic changes in dry heat resistance of Bacillus subtilis spores after rapid changes in pH. Heat resistance of freeze-dried Bacillus subtilis spores varied in a rhythmic manner as a function of time between acidification to about pH 1.5 and freezing. A comparable rapid shift to pH 11 produced little change in resistance to heat."}
{"id": "PMID:235905", "title": "Lymphomatoid granulomatosis of the skin. A new clinocopathologic entity.", "content": "Lymphomatoid granulomatosis is a necrotizing arteritis primarily affecting the lungs but also found in the skin, kidneys, central nervous system, and other extra-pulmonary sites. Cutaneous involvement occurred in 45% of the cases described by Liebow in his original series. Light microscopy studies were performed. The IgA and IgG levels were slightly decreased and the IgE level was elevated. Cell-mediated immunity was impaired. No viruses were isolated or identified by immunofluorescence. A man had cutaneous lesions as the first sign of lymphomatoid granulomatosis.", "contents": "Lymphomatoid granulomatosis of the skin. A new clinocopathologic entity. Lymphomatoid granulomatosis is a necrotizing arteritis primarily affecting the lungs but also found in the skin, kidneys, central nervous system, and other extra-pulmonary sites. Cutaneous involvement occurred in 45% of the cases described by Liebow in his original series. Light microscopy studies were performed. The IgA and IgG levels were slightly decreased and the IgE level was elevated. Cell-mediated immunity was impaired. No viruses were isolated or identified by immunofluorescence. A man had cutaneous lesions as the first sign of lymphomatoid granulomatosis."}
{"id": "PMID:235907", "title": "Arbovirus infections in Sarawak, October 1968--February 1970 Tembusu and Sindbis virus isolations from mosquitoes.", "content": "Thirty isolations of Tembusu virus and four of Sindbis virus were obtained from approximately 280 000 mosquitoes collected between October 1968 and February 1970 in Sarawak, particularly from K. Tijirak, a Land Dyak village 19 miles South of Kuching. Twenty-two isolations of Tembusu virus and two of Sindbis virus were from Culex tritaeniorhynchus; two of Tembusu virus and two of Sindbis virus came from Culex gelidus. Tembusu virus was active throughout the year at K. Tijirak, the highest infection rates in C. tritaeniorhynchus being in January-March and May-August, when the C. tritaeniorhynchus population was declining and ageing. These results confirm that C. tritaeniorhynchus is the principal arthopod host of Tembusu virus in Sarawak. Antibody studies suggest that birds, particularly domestic fowl, are probably vertebrate maintenance hosts of Tembusu and Sindbis viruses in Sarawak.", "contents": "Arbovirus infections in Sarawak, October 1968--February 1970 Tembusu and Sindbis virus isolations from mosquitoes. Thirty isolations of Tembusu virus and four of Sindbis virus were obtained from approximately 280 000 mosquitoes collected between October 1968 and February 1970 in Sarawak, particularly from K. Tijirak, a Land Dyak village 19 miles South of Kuching. Twenty-two isolations of Tembusu virus and two of Sindbis virus were from Culex tritaeniorhynchus; two of Tembusu virus and two of Sindbis virus came from Culex gelidus. Tembusu virus was active throughout the year at K. Tijirak, the highest infection rates in C. tritaeniorhynchus being in January-March and May-August, when the C. tritaeniorhynchus population was declining and ageing. These results confirm that C. tritaeniorhynchus is the principal arthopod host of Tembusu virus in Sarawak. Antibody studies suggest that birds, particularly domestic fowl, are probably vertebrate maintenance hosts of Tembusu and Sindbis viruses in Sarawak."}
{"id": "PMID:235908", "title": "Management of flail chest without mechanical ventilation.", "content": "The pathophysiology of flail chest is usually described only on the basis of paradoxical respiration, ignoring underlying pulmonary contusion. Two groups of comparable patients were treated either with early tracheal intubation and mechanical ventilation (Group 1), or with fluid restriction, diuretics, methylpredinisolone, albumin, vigorous pulmonary toilet, and intercostal nerve blocks, ignoring the paradox and treating only the underlying lung (Group 2). When tracheostomy and mechanical ventilation were not used the mortality rate went from 21% to O(p = 0.01), the complication rate from 100% to 20% (p = 0.005), and the average hospitalization from 31.3 to 9.3 days (p = 0.005). We conclude that most patients with flail chest do not need internal pneumatic stabilization if the underlying lung is treated appropriately and that tracheostomy and prolonged mechanical ventilation with a volume respirator, as practiced in most respiratory care centers, is usually a triumph of technique over judgment.", "contents": "Management of flail chest without mechanical ventilation. The pathophysiology of flail chest is usually described only on the basis of paradoxical respiration, ignoring underlying pulmonary contusion. Two groups of comparable patients were treated either with early tracheal intubation and mechanical ventilation (Group 1), or with fluid restriction, diuretics, methylpredinisolone, albumin, vigorous pulmonary toilet, and intercostal nerve blocks, ignoring the paradox and treating only the underlying lung (Group 2). When tracheostomy and mechanical ventilation were not used the mortality rate went from 21% to O(p = 0.01), the complication rate from 100% to 20% (p = 0.005), and the average hospitalization from 31.3 to 9.3 days (p = 0.005). We conclude that most patients with flail chest do not need internal pneumatic stabilization if the underlying lung is treated appropriately and that tracheostomy and prolonged mechanical ventilation with a volume respirator, as practiced in most respiratory care centers, is usually a triumph of technique over judgment."}
{"id": "PMID:235909", "title": "Exercise tolerance after repair of tetralogy of Fallot.", "content": "Twelve patients who had undergone complete repair of tetralogy of Fallot at ages ranging from 8 to 27 years were studied for exercise tolerance several years later. Work performance ranged from 58 to 130% of that predicted. Increased physiological dead space and alveolar-arterial Po2 difference at exercise suggested pulmonary vascular disease, which was confirmed in 1 patient by pulmonary angiography. Excercise tolerance decreased with increasing age at time of repair, underlining the desirability of early corrective operation.", "contents": "Exercise tolerance after repair of tetralogy of Fallot. Twelve patients who had undergone complete repair of tetralogy of Fallot at ages ranging from 8 to 27 years were studied for exercise tolerance several years later. Work performance ranged from 58 to 130% of that predicted. Increased physiological dead space and alveolar-arterial Po2 difference at exercise suggested pulmonary vascular disease, which was confirmed in 1 patient by pulmonary angiography. Excercise tolerance decreased with increasing age at time of repair, underlining the desirability of early corrective operation."}
{"id": "PMID:235910", "title": "Labeling effects in psychiatric hospitalization. A study of diverging patterns of inpatient self-labeling processes.", "content": "This report explores two theoretical positions regarding psychiatric inpatient self-labeling processes over time. One position suggests that acceptance of the deviant label \"mentally ill\" is benign; the other suggests that such label acceptance may be harmful to patients. Employing empirical, longitudinal data from a sample of 43 inpatients, three complex, but discernible, patterns of \"acceptance,\" \"rejection,\" or \"denial\" of the \"deviant\" label of mental patient emerged over time within a short-term hospital setting. The three patient groups varied on Minnesota Multiphasic Personality Inventory scales, staff behavioral ratings over time, involvement in approved ward activities, and length of hospitalization. Results were discussed in terms of patient-staff interaction and its possible relation to patient self-labeling.", "contents": "Labeling effects in psychiatric hospitalization. A study of diverging patterns of inpatient self-labeling processes. This report explores two theoretical positions regarding psychiatric inpatient self-labeling processes over time. One position suggests that acceptance of the deviant label \"mentally ill\" is benign; the other suggests that such label acceptance may be harmful to patients. Employing empirical, longitudinal data from a sample of 43 inpatients, three complex, but discernible, patterns of \"acceptance,\" \"rejection,\" or \"denial\" of the \"deviant\" label of mental patient emerged over time within a short-term hospital setting. The three patient groups varied on Minnesota Multiphasic Personality Inventory scales, staff behavioral ratings over time, involvement in approved ward activities, and length of hospitalization. Results were discussed in terms of patient-staff interaction and its possible relation to patient self-labeling."}
{"id": "PMID:235911", "title": "Cerebral vasculitis in rheumatoid arthritis.", "content": "A 63-year-old man with severe, untreated rheumatoid arthritis and pleuritis developed an unusual neurological syndrome similar to Gerstman syndrome, followed by dementia and blindness, six weeks before his death. An autopsy showed extensive necrotizing vasculitis, resembling polyarteritis nodosa, involving the brain and resulting in numerous infarcts. The disease was most severe in the posterior portion of the cerebral hemispheres. Other organs were only slightly involved. Severe amyloidosis of cerebral arterioles and senile plaques were noted in the areas of brain with most severe vasculitis. Review of literature indicated only six cases of cerebral vasculitis in rheumatoid disease, five of which were treated with corticosteroids.", "contents": "Cerebral vasculitis in rheumatoid arthritis. A 63-year-old man with severe, untreated rheumatoid arthritis and pleuritis developed an unusual neurological syndrome similar to Gerstman syndrome, followed by dementia and blindness, six weeks before his death. An autopsy showed extensive necrotizing vasculitis, resembling polyarteritis nodosa, involving the brain and resulting in numerous infarcts. The disease was most severe in the posterior portion of the cerebral hemispheres. Other organs were only slightly involved. Severe amyloidosis of cerebral arterioles and senile plaques were noted in the areas of brain with most severe vasculitis. Review of literature indicated only six cases of cerebral vasculitis in rheumatoid disease, five of which were treated with corticosteroids."}
{"id": "PMID:235916", "title": "[Production of histological preparations from implanted vascular protheses (author's transl)].", "content": "The above mentioned method is suitable for the production of intact histological preparations of implanted vascular protheses. An even mounting of the sections is as possible as the application of the usual staining procedures except those containing methanol or any other agent dissolving collodion.", "contents": "[Production of histological preparations from implanted vascular protheses (author's transl)]. The above mentioned method is suitable for the production of intact histological preparations of implanted vascular protheses. An even mounting of the sections is as possible as the application of the usual staining procedures except those containing methanol or any other agent dissolving collodion."}
{"id": "PMID:235938", "title": "The aetiology, characteristics and diagnostic relevance of late deceleration patterns in routine obstetric practice.", "content": "A retrospective study is described in which all the late deceleration patterns seen in one obstetric unit over the course of 34 months have been reviewed with regard to their apparent aetiology, their characteristics and associated abnormal fetal heart rate patterns and the incidence of fetal distress. The results show that, regardless of the aetiology and the characteristics, the incidence of fetal distress (defined as a pH of less than 7-25 or an Apgar score of less than 7 at one minute) lies between 40 and 50 per cent. The implications of this degree of diagnostic inaccuracy are discussed and the importance of fetal blood sampling as the final arbiter in the diagnosis is emphasized. During the course of the study a significant relationship was demonstrated between the use of epidural analgesia and the incidence of late deceleration patterns. This finding is discussed.", "contents": "The aetiology, characteristics and diagnostic relevance of late deceleration patterns in routine obstetric practice. A retrospective study is described in which all the late deceleration patterns seen in one obstetric unit over the course of 34 months have been reviewed with regard to their apparent aetiology, their characteristics and associated abnormal fetal heart rate patterns and the incidence of fetal distress. The results show that, regardless of the aetiology and the characteristics, the incidence of fetal distress (defined as a pH of less than 7-25 or an Apgar score of less than 7 at one minute) lies between 40 and 50 per cent. The implications of this degree of diagnostic inaccuracy are discussed and the importance of fetal blood sampling as the final arbiter in the diagnosis is emphasized. During the course of the study a significant relationship was demonstrated between the use of epidural analgesia and the incidence of late deceleration patterns. This finding is discussed."}
{"id": "PMID:235939", "title": "Beta-mimetic drugs and possible prevention of respiratory distress syndrome.", "content": "The prophylactic value of beta-mimetic drugs in preventing respiratory distress syndrome (RDS) is investigated by comparing 29 preterm infants of ritodrine treated mothers with 34 preterm infants of a control group. Five cases of RDS (17 per cent) occurred among the infants of treated mothers as compared with 12 cases (35 per cent) in the control group (p = 0-09). The difference is, however, statistically significant for the group of infants weighing less than 2300 grams (p = 0-01) which includes all infants affected with RDS.", "contents": "Beta-mimetic drugs and possible prevention of respiratory distress syndrome. The prophylactic value of beta-mimetic drugs in preventing respiratory distress syndrome (RDS) is investigated by comparing 29 preterm infants of ritodrine treated mothers with 34 preterm infants of a control group. Five cases of RDS (17 per cent) occurred among the infants of treated mothers as compared with 12 cases (35 per cent) in the control group (p = 0-09). The difference is, however, statistically significant for the group of infants weighing less than 2300 grams (p = 0-01) which includes all infants affected with RDS."}
{"id": "PMID:235940", "title": "The effect of different feeds, including those containing soya-bean products, on the passage of digesta from the abomasum of the preruminant calf.", "content": "1. The effects of various factors on rates of flow and composition of digesta leaving the abomasum of preruminant calves were studied. The possible relation of some of these effects to the development of serum antibodies to certain dietary constituents has also been examined. Two situations were distinguished: (a) unsensitized responses, shown by calves receiving milk protein or soya-bean products for the first one or two occasions; (b) sensitized responses, shown by calves receiving certain soya-bean products, after a number of these feeds had been given. 2. For unsensitized calves, the rate of flow of total digesta from the abomasum was greater in the first few hours after a feed consisting of a mineral solution was given, than after cow's milk was given. This difference wasapparently due to differences in the composition of digesta entering the duodenum. Total digesta flows after giving synthetic milk feeds, prepared from different protein sources, were similar to those after cow's milk was given. 3. For sensitized calves, rates of flow of total digesta from the abomasum were greatly affected by the nature of the protein source used in the diet. Soya-bean flour (heated or unheated) generally caused inhibition of flow for some hours after feeding; a soya-bean protein isolate (isoelectric) had a similar but smaller effect, but a soya-bean concentrate (prepared by alcohol extraction of a soya-bean flour) and milk protein had little or no effect. The inhibition, believed to be a sign of more general disorders, appeared to be caused by a factor entering the duodenum which induced a change in the way in which the calf responded, probably as the result of a gastrointestinal allergy. 4. Calves given soya-bean flour or a soya-bean protein isolate (isoelectric) in their diets for several weeks, showed respectively high and low titres of serum antibodies to an antigen prepared from soya-bean flour. Calves given alcohol-extracted soya-bean concentrate had no similar antibodies. 5. In addition to variations in total digesta flow, dietary nitrogen compounds were held up in the abomasum to different extents after different feeds. After a whole-milk feed or a synthetic feed prepared from casein, a slow, steady release of N occurred over at least 9 h. N hold-up after giving soya-bean-containing feeds was slight for the soya-bean flour, but extremely marked for the soya-bean protein isolate (isoelectric). The latter hold-up was followed after several hours by a rapid outflow of N from the abomasum.", "contents": "The effect of different feeds, including those containing soya-bean products, on the passage of digesta from the abomasum of the preruminant calf. 1. The effects of various factors on rates of flow and composition of digesta leaving the abomasum of preruminant calves were studied. The possible relation of some of these effects to the development of serum antibodies to certain dietary constituents has also been examined. Two situations were distinguished: (a) unsensitized responses, shown by calves receiving milk protein or soya-bean products for the first one or two occasions; (b) sensitized responses, shown by calves receiving certain soya-bean products, after a number of these feeds had been given. 2. For unsensitized calves, the rate of flow of total digesta from the abomasum was greater in the first few hours after a feed consisting of a mineral solution was given, than after cow's milk was given. This difference wasapparently due to differences in the composition of digesta entering the duodenum. Total digesta flows after giving synthetic milk feeds, prepared from different protein sources, were similar to those after cow's milk was given. 3. For sensitized calves, rates of flow of total digesta from the abomasum were greatly affected by the nature of the protein source used in the diet. Soya-bean flour (heated or unheated) generally caused inhibition of flow for some hours after feeding; a soya-bean protein isolate (isoelectric) had a similar but smaller effect, but a soya-bean concentrate (prepared by alcohol extraction of a soya-bean flour) and milk protein had little or no effect. The inhibition, believed to be a sign of more general disorders, appeared to be caused by a factor entering the duodenum which induced a change in the way in which the calf responded, probably as the result of a gastrointestinal allergy. 4. Calves given soya-bean flour or a soya-bean protein isolate (isoelectric) in their diets for several weeks, showed respectively high and low titres of serum antibodies to an antigen prepared from soya-bean flour. Calves given alcohol-extracted soya-bean concentrate had no similar antibodies. 5. In addition to variations in total digesta flow, dietary nitrogen compounds were held up in the abomasum to different extents after different feeds. After a whole-milk feed or a synthetic feed prepared from casein, a slow, steady release of N occurred over at least 9 h. N hold-up after giving soya-bean-containing feeds was slight for the soya-bean flour, but extremely marked for the soya-bean protein isolate (isoelectric). The latter hold-up was followed after several hours by a rapid outflow of N from the abomasum."}
{"id": "PMID:235941", "title": "A relationship between the molar proportion of propionic acid and the clearance rate of the liquid phase in the rumen of the sheep.", "content": "1. Four rumen-cannulated sheep were given a forage mixture (F) of chopped hay-ground, pelleted, dried grass (92:8, w/w) and two concentrate mixtures (C and S) of ground barley-ground hay-flaked maize (46:24:30 and 56:24:20, by wt respectively) in twenty-four hourly meals each day. Each of the diets was offered in successive periods of 16 d to give a feeding sequence F-S-C-S for one pair of sheep and C-S-F-S for the other pair. 2. The average composition (mol/100 mol) of the mixture of short-chain fatty acids, acetic, propionic and butyric, in the rumen was respectively 70-1, 18-5 and 7-5 with diet F, and 55-8, 24-8 and 13-6 with diet C. With diet S, the pattern of fermentation varied both between animals and in the same animal for different periods having either 'high' (28-39 mol/100 mol) or 'low' (16-21 mol/100 mol) proportions of propionic acid. On average when diet S followed diet F there was less propionic acid in the fermentation mixture than when diet S followed diet C (59-3 acetic, 22-2 propionic and 14-1 butyric as compared with 52-7, 29-4 and 13-1 respectively) but this trend was not significant and there was evidence of interactions between the feeding sequences and the individual sheep. 3. The mean concentrations of ammonia, sodium, potassium and chloride were similar for all diets but the pH and concentrations of calcium, magnesium and phosphorus tended to be higher and the buffering capacity lower for diet F than for diets C or S. In animals receiving diet S there was no relationship between the concentrations of minerals, the pH or buffering capacity and the pattern of fermentation except for ammonia, the concentration of which was high when the molar proportion of propionic acid was low. 4. Rumen volume, outflow rate and clearance rate, determined using polyethylene glycol, were higher for diet F than for diets C and S but within each diet, particularly for diet S, values varied considerably between sheep and between periods. 5. There was evidence of an interrelationship between the molar proportion of propionic acid in the fermentation products and the clearance rate, which indicated that the clearance rate may be an important factor influencing the pattern of fermentation in the rumen.", "contents": "A relationship between the molar proportion of propionic acid and the clearance rate of the liquid phase in the rumen of the sheep. 1. Four rumen-cannulated sheep were given a forage mixture (F) of chopped hay-ground, pelleted, dried grass (92:8, w/w) and two concentrate mixtures (C and S) of ground barley-ground hay-flaked maize (46:24:30 and 56:24:20, by wt respectively) in twenty-four hourly meals each day. Each of the diets was offered in successive periods of 16 d to give a feeding sequence F-S-C-S for one pair of sheep and C-S-F-S for the other pair. 2. The average composition (mol/100 mol) of the mixture of short-chain fatty acids, acetic, propionic and butyric, in the rumen was respectively 70-1, 18-5 and 7-5 with diet F, and 55-8, 24-8 and 13-6 with diet C. With diet S, the pattern of fermentation varied both between animals and in the same animal for different periods having either 'high' (28-39 mol/100 mol) or 'low' (16-21 mol/100 mol) proportions of propionic acid. On average when diet S followed diet F there was less propionic acid in the fermentation mixture than when diet S followed diet C (59-3 acetic, 22-2 propionic and 14-1 butyric as compared with 52-7, 29-4 and 13-1 respectively) but this trend was not significant and there was evidence of interactions between the feeding sequences and the individual sheep. 3. The mean concentrations of ammonia, sodium, potassium and chloride were similar for all diets but the pH and concentrations of calcium, magnesium and phosphorus tended to be higher and the buffering capacity lower for diet F than for diets C or S. In animals receiving diet S there was no relationship between the concentrations of minerals, the pH or buffering capacity and the pattern of fermentation except for ammonia, the concentration of which was high when the molar proportion of propionic acid was low. 4. Rumen volume, outflow rate and clearance rate, determined using polyethylene glycol, were higher for diet F than for diets C and S but within each diet, particularly for diet S, values varied considerably between sheep and between periods. 5. There was evidence of an interrelationship between the molar proportion of propionic acid in the fermentation products and the clearance rate, which indicated that the clearance rate may be an important factor influencing the pattern of fermentation in the rumen."}
{"id": "PMID:235942", "title": "On the DNA polymerase III of mouse myeloma: partial purification and characterization.", "content": "A high molecular weight membrane-bound DNA polymerase from the mouse myeloma, MOPC-104E, has been purified extensively, and characterized with regard to physical and reaction properties. This enzyme, which is readily distinguishable from other myeloma enzymes that are analogous to the recognized forms of cellular DNA polymerase, is ddesignated DNA polymerase III. DNA polymerase III activity in whole homogenates from MOPC-104E was solubilized and then prurifed using a series of ion-exchange chromatographic procedures followed by DNA-cellulose chromatography and glycerol gradient centrifugation; the enzyme activity as measured with poly(rA)-(dT)12-18 as template-primer and Mn2+ as divalent cation, was purified as much as 18,000-fold. In the final stages of the pruification, DNA polymerase III possessed no detectable RNA polymerase activity, nucleoside diphosphokinase activity, or nucease activity toward DNA or single- and double-stranded RNA...", "contents": "On the DNA polymerase III of mouse myeloma: partial purification and characterization. A high molecular weight membrane-bound DNA polymerase from the mouse myeloma, MOPC-104E, has been purified extensively, and characterized with regard to physical and reaction properties. This enzyme, which is readily distinguishable from other myeloma enzymes that are analogous to the recognized forms of cellular DNA polymerase, is ddesignated DNA polymerase III. DNA polymerase III activity in whole homogenates from MOPC-104E was solubilized and then prurifed using a series of ion-exchange chromatographic procedures followed by DNA-cellulose chromatography and glycerol gradient centrifugation; the enzyme activity as measured with poly(rA)-(dT)12-18 as template-primer and Mn2+ as divalent cation, was purified as much as 18,000-fold. In the final stages of the pruification, DNA polymerase III possessed no detectable RNA polymerase activity, nucleoside diphosphokinase activity, or nucease activity toward DNA or single- and double-stranded RNA..."}
{"id": "PMID:235943", "title": "Mitochondrial poly(A) polymerase from a poorly differentiated hepatoma: purification and characteristics.", "content": "Poly(A) polymerase (EC 2.7.7.19) solubilized from mitochondria of a poorly differentiated rat tumor, Morris hepatoma 3924A, was purified more than 1000-fold by successive column chromatography on phosphocellulose, DEAE-Sephadex, and hydroxylapatite. Purified enzyme catalyzed the incorporation of ATP into poly(A) only upon addition of an exogenous primer. Of several primers tested, synthetic poly(A) was the most effective. The enzyme utilized mitochondrial RNA as a primer at least five times as efficiently as nuclear RNA. The enzyme required Mn2+, and had a pH optimum of 7.8-8.2. The enzyme utilized ATP exclusively as a substrate; the calculated K-m for ATP was 28 muM. The polymerization reaction was not inhibited by RNase, ethidium bromide, distamycin, or alpha-amanitin. The reaction was sensitive to O-n-octyloxime of 3-formylrifamycin SV (AF/013). As estimated from glycerol gradient centrifugation and acrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, the molecular weight of the enzyme was 60,000. The product was covalently linked to the polynucleotide primer and the average length of the poly(A) formed was 600 nucleotides.", "contents": "Mitochondrial poly(A) polymerase from a poorly differentiated hepatoma: purification and characteristics. Poly(A) polymerase (EC 2.7.7.19) solubilized from mitochondria of a poorly differentiated rat tumor, Morris hepatoma 3924A, was purified more than 1000-fold by successive column chromatography on phosphocellulose, DEAE-Sephadex, and hydroxylapatite. Purified enzyme catalyzed the incorporation of ATP into poly(A) only upon addition of an exogenous primer. Of several primers tested, synthetic poly(A) was the most effective. The enzyme utilized mitochondrial RNA as a primer at least five times as efficiently as nuclear RNA. The enzyme required Mn2+, and had a pH optimum of 7.8-8.2. The enzyme utilized ATP exclusively as a substrate; the calculated K-m for ATP was 28 muM. The polymerization reaction was not inhibited by RNase, ethidium bromide, distamycin, or alpha-amanitin. The reaction was sensitive to O-n-octyloxime of 3-formylrifamycin SV (AF/013). As estimated from glycerol gradient centrifugation and acrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, the molecular weight of the enzyme was 60,000. The product was covalently linked to the polynucleotide primer and the average length of the poly(A) formed was 600 nucleotides."}
{"id": "PMID:235944", "title": "Thermal transitions of myosin and its helical fragments. I. Shifts in proton equilibria accompanying unfolding.", "content": "The thermal transitions of myosin and its helical fragments have been studied with pH as the observable. Heating unbuffered solutions of these proteins near their pI values causes an abrupt rise in pH at a characteristic temperature (the \"melting temperature,\" Tm) which is due to structural changes within the protein. Since the pH shift turns out to be insensitive to the degree of protein aggregation, we have obtained acceptable melting curves even under conditions where the protein coagulates during melting. The melting profiles and Tm vlaues of myosin, myosin rod, and light meromyosin have been found to be remarkably similar (Tm equal to 40 plus or minus 1 degree, 0.5 M KCl, pH 5.9). Proton binding which occurs during melting coincides with the unfolding of a section of myosin rod. Taken in the context of other studies, the proton binding is thought to occur near the \"hinge region.\"", "contents": "Thermal transitions of myosin and its helical fragments. I. Shifts in proton equilibria accompanying unfolding. The thermal transitions of myosin and its helical fragments have been studied with pH as the observable. Heating unbuffered solutions of these proteins near their pI values causes an abrupt rise in pH at a characteristic temperature (the \"melting temperature,\" Tm) which is due to structural changes within the protein. Since the pH shift turns out to be insensitive to the degree of protein aggregation, we have obtained acceptable melting curves even under conditions where the protein coagulates during melting. The melting profiles and Tm vlaues of myosin, myosin rod, and light meromyosin have been found to be remarkably similar (Tm equal to 40 plus or minus 1 degree, 0.5 M KCl, pH 5.9). Proton binding which occurs during melting coincides with the unfolding of a section of myosin rod. Taken in the context of other studies, the proton binding is thought to occur near the \"hinge region.\""}
{"id": "PMID:235945", "title": "Thermal transitions of myosin and its helical fragments. II. Solvent-induced variations in conformational stability.", "content": "The melting behavior of myosin and myosin rod has been studied over the pH range 5.4-7.0, in 0.5 M KCl. Both proteins exhibit almost identical T-m values, which increase from about  37 to 43 degrees as the pH is elevated through the range of study, T-m follows a sigmoidal dependence upon pH, and the inflection point occurs near pH 6.5. The influence of salt concentration on T-m was studied, by the variation of KCl from 0.15 to 2.92 M. With an increasing KCl concentration, both proteins exhibit similar, sigmoidal declines in T-m from about 44 to 34 degrees. Under all conditions of pH and ionic strength studied, melting is accompanied by an absorption of H+ by the protein. The concentration of the protein, the age of the preparation, and the presence of divalent metal ions fail to exert a significant effect on the T-m values obtained by our methods. The effects of salt concentration and pH on the thermal stability of myosin and myosin rod are discussed in terms of the location of the melting process within the myosin molecule. Myosin is shown to possess several of the requisite features for energy transduction via a proton-coupling mechanism. These features provide a framework for investigating some aspects of the molecular basis of muscle contraction within the context of the sliding filament model.", "contents": "Thermal transitions of myosin and its helical fragments. II. Solvent-induced variations in conformational stability. The melting behavior of myosin and myosin rod has been studied over the pH range 5.4-7.0, in 0.5 M KCl. Both proteins exhibit almost identical T-m values, which increase from about  37 to 43 degrees as the pH is elevated through the range of study, T-m follows a sigmoidal dependence upon pH, and the inflection point occurs near pH 6.5. The influence of salt concentration on T-m was studied, by the variation of KCl from 0.15 to 2.92 M. With an increasing KCl concentration, both proteins exhibit similar, sigmoidal declines in T-m from about 44 to 34 degrees. Under all conditions of pH and ionic strength studied, melting is accompanied by an absorption of H+ by the protein. The concentration of the protein, the age of the preparation, and the presence of divalent metal ions fail to exert a significant effect on the T-m values obtained by our methods. The effects of salt concentration and pH on the thermal stability of myosin and myosin rod are discussed in terms of the location of the melting process within the myosin molecule. Myosin is shown to possess several of the requisite features for energy transduction via a proton-coupling mechanism. These features provide a framework for investigating some aspects of the molecular basis of muscle contraction within the context of the sliding filament model."}
{"id": "PMID:235946", "title": "Analysis of cooperativity in hemoglobin. Valency hybrids, oxidation, and methemoglobin replacement reactions.", "content": "An allosteric model proposed previously for structure-function relations in hemoglobin is applied to the analysis of low- and high-spin valency hybrids. By assuming that the low-spin oxidized chains have the tertiary structure of oxygenated chains while the high-spin oxidized chains have a tertiary structure intermediate between that of deoxygenated and oxygenated chains, the model parameters associated with the different valency hybrids can be obtained, and their equilibrium properties can be estimated. The hybrid results are used also to provide an interpretation of methemoglobin and its ligand replacement reactions and of the oxidation-reduction equilibrium of normal hemoglobin. For the various systems studied it is found that the effects of pH and 2,3-diphosphoglycerate are in agreement with the model.", "contents": "Analysis of cooperativity in hemoglobin. Valency hybrids, oxidation, and methemoglobin replacement reactions. An allosteric model proposed previously for structure-function relations in hemoglobin is applied to the analysis of low- and high-spin valency hybrids. By assuming that the low-spin oxidized chains have the tertiary structure of oxygenated chains while the high-spin oxidized chains have a tertiary structure intermediate between that of deoxygenated and oxygenated chains, the model parameters associated with the different valency hybrids can be obtained, and their equilibrium properties can be estimated. The hybrid results are used also to provide an interpretation of methemoglobin and its ligand replacement reactions and of the oxidation-reduction equilibrium of normal hemoglobin. For the various systems studied it is found that the effects of pH and 2,3-diphosphoglycerate are in agreement with the model."}
{"id": "PMID:235947", "title": "Hydrolysis of ribonucleoside 3'-diphosphates by rye grass 3'-nucleotidase.", "content": "Rye grass 3'-nucleotidase has been purified to apparent homogeneity on Sephadex A-25 and CM-cellulose columns and shown to hydrolyze 2'-O-methyladenosine 3'-monophohate and 2'-deoxyadenosine 3'-monophosphate 35.8 and 542 times more slowly than the normal substrate (3'-AMP), verifying the importance of the 2'-beta-OH group of the substrate in the overall hydrolysis process. Although neither was hydrolyzed as rapidly as 3'-AMP, both the 2'-O-methyl and 2'-deoxy analogs acted as competitive inhibitors of the hydrolysis of 3'-AMP (K-m equals 0.12 mM), with apparent K-i's of 0.39 and 0.51 nM, respectively. In order to determine the possible susceptibility of naturally occurring ribonucleoside 3'-diphosphates, such as guanosine tetraphosphate (ppGpp), to 3'-phosphohydrolase activities, the 3'-nucleotidase was also employed in the attempted pyrophosphorolysis of adenosine 3'-diphosphate and guanosine tetraphosphate. Neither adenosine 3'-diphosphate nor guanosine tetraphosphate was degraded at a significant rate by the nucleotidase, relative to the normal substrate.", "contents": "Hydrolysis of ribonucleoside 3'-diphosphates by rye grass 3'-nucleotidase. Rye grass 3'-nucleotidase has been purified to apparent homogeneity on Sephadex A-25 and CM-cellulose columns and shown to hydrolyze 2'-O-methyladenosine 3'-monophohate and 2'-deoxyadenosine 3'-monophosphate 35.8 and 542 times more slowly than the normal substrate (3'-AMP), verifying the importance of the 2'-beta-OH group of the substrate in the overall hydrolysis process. Although neither was hydrolyzed as rapidly as 3'-AMP, both the 2'-O-methyl and 2'-deoxy analogs acted as competitive inhibitors of the hydrolysis of 3'-AMP (K-m equals 0.12 mM), with apparent K-i's of 0.39 and 0.51 nM, respectively. In order to determine the possible susceptibility of naturally occurring ribonucleoside 3'-diphosphates, such as guanosine tetraphosphate (ppGpp), to 3'-phosphohydrolase activities, the 3'-nucleotidase was also employed in the attempted pyrophosphorolysis of adenosine 3'-diphosphate and guanosine tetraphosphate. Neither adenosine 3'-diphosphate nor guanosine tetraphosphate was degraded at a significant rate by the nucleotidase, relative to the normal substrate."}
{"id": "PMID:235948", "title": "Ribonucleoside 3'-di- and -triphosphates. Synthesis of guanosine tetraphosphate (ppGpp).", "content": "A procedure has been outlined for the synthesis of ribonucleoside 3'-di- and -triphosphates. The synthetic scheme involves the conversion of a ribonucleoside 3'-monophosphate to its 2'-(5'-di)-O-(1-methoxyethyl) derivative, followed by successive treatments of the blocked ribonucleotide with 1,1'-carbonyldiimidazole and mono(tri-n-butylammonium) phosphate or pyrophosphate. The resulting ribonucleoside 3'-di- and -triphosphate derivatives are then deblocked by treatment with dilute aqueous acetic acid, pH 3.0. The use of this procedure is illustrated for adenosine 3'-monophosphate, which has been converted to its corresponding 3'-di- and -triphosphates in 61% overall yield. The decomposition of adenosine 3'-di- and -triphosphates to adenosine 2'-monophosphate, adenosine 3'-monophosphate, and adenosine cyclic 2',3'-monophosphate as a function of pH at 100 degrees has been studied as has the attempted polymerization of adenosine 3'-diphosphate with polynucleotide phosphorylase. Also prepared was guanosine 5'-diphosphate 3'-diphosphate (guanosine tetraphosphate; ppGpp), which was accessible via treatment of 2'-O-(1-methoxyethyl)guanosine 5'-monophosphate 3'-monophosphate with the phosphorimidazolidate of mono(tri-n-butyl ammonium) phosphate. The resulting blocked tetraphosphate was deblocked in dilute aqueous acetic acid to afford ppGpp in an overall yield of 18%.", "contents": "Ribonucleoside 3'-di- and -triphosphates. Synthesis of guanosine tetraphosphate (ppGpp). A procedure has been outlined for the synthesis of ribonucleoside 3'-di- and -triphosphates. The synthetic scheme involves the conversion of a ribonucleoside 3'-monophosphate to its 2'-(5'-di)-O-(1-methoxyethyl) derivative, followed by successive treatments of the blocked ribonucleotide with 1,1'-carbonyldiimidazole and mono(tri-n-butylammonium) phosphate or pyrophosphate. The resulting ribonucleoside 3'-di- and -triphosphate derivatives are then deblocked by treatment with dilute aqueous acetic acid, pH 3.0. The use of this procedure is illustrated for adenosine 3'-monophosphate, which has been converted to its corresponding 3'-di- and -triphosphates in 61% overall yield. The decomposition of adenosine 3'-di- and -triphosphates to adenosine 2'-monophosphate, adenosine 3'-monophosphate, and adenosine cyclic 2',3'-monophosphate as a function of pH at 100 degrees has been studied as has the attempted polymerization of adenosine 3'-diphosphate with polynucleotide phosphorylase. Also prepared was guanosine 5'-diphosphate 3'-diphosphate (guanosine tetraphosphate; ppGpp), which was accessible via treatment of 2'-O-(1-methoxyethyl)guanosine 5'-monophosphate 3'-monophosphate with the phosphorimidazolidate of mono(tri-n-butyl ammonium) phosphate. The resulting blocked tetraphosphate was deblocked in dilute aqueous acetic acid to afford ppGpp in an overall yield of 18%."}
{"id": "PMID:235949", "title": "Proton magnetic resonance titration curves of the three histidine residues of staphylococcal protease.", "content": "Proton magnetic resonance spectra of staphylococcal protease, a serine protease from Staphylococcus aureus, strain V8, are presented. Initial proton spectra were obtained at 220 MHz, and more detailed studies of the aromatic region were carried out by correlation spectroscopy at 250 MHz. The overall spectrum bears a close resemblance to one calculated from the sum of spectra of the component amino acids. Chemical shifts of the three tyrosine, four phenylalanine, and three histidine residues appear to be equivalent at pH 3.7 and 8.5 indicating that they are all in normal chemical environments in the enzyme. The staphylococcal protease contains a large number of slowly exchanging protons. In fact, interpretable spectra of the aromatic region were obtained only after extensive exchange of N-H groups with deuterium from the D2O solvent. Proton magnetic resonance titration studies of the three histidine residues indicate that these have normal chemical shifts and pK' values. When the data are fitted to single noninteracting titration curves, the histidine pK' values are 7.19 plus or minus 0.02, 6.85 plus or minus 0.03, and 6.69 plus or minus 0.02. The titration curves of two of the histidine residues indicate negative cooperativity. A possible explanation for this is a direct electrostatic interaction between the two histidines. The titration data for these histidines give a significantly better fit to such a mutual interaction model than to noninteracting titration curves. The component microscopic dissociation constants have been calculated. Mutual interaction leads to pK' displacements of 0.31 unit; which indicates a distance of approximately 7 angstrom between the two interacting histidine rings according to the model of Tanford and Roxby. The proton resonances of the two interacting histidines are doubled in the pH region 6.7-7.0 suggesting the presence of two forms of the enzyme having lifetimes in excess of 30 msec.", "contents": "Proton magnetic resonance titration curves of the three histidine residues of staphylococcal protease. Proton magnetic resonance spectra of staphylococcal protease, a serine protease from Staphylococcus aureus, strain V8, are presented. Initial proton spectra were obtained at 220 MHz, and more detailed studies of the aromatic region were carried out by correlation spectroscopy at 250 MHz. The overall spectrum bears a close resemblance to one calculated from the sum of spectra of the component amino acids. Chemical shifts of the three tyrosine, four phenylalanine, and three histidine residues appear to be equivalent at pH 3.7 and 8.5 indicating that they are all in normal chemical environments in the enzyme. The staphylococcal protease contains a large number of slowly exchanging protons. In fact, interpretable spectra of the aromatic region were obtained only after extensive exchange of N-H groups with deuterium from the D2O solvent. Proton magnetic resonance titration studies of the three histidine residues indicate that these have normal chemical shifts and pK' values. When the data are fitted to single noninteracting titration curves, the histidine pK' values are 7.19 plus or minus 0.02, 6.85 plus or minus 0.03, and 6.69 plus or minus 0.02. The titration curves of two of the histidine residues indicate negative cooperativity. A possible explanation for this is a direct electrostatic interaction between the two histidines. The titration data for these histidines give a significantly better fit to such a mutual interaction model than to noninteracting titration curves. The component microscopic dissociation constants have been calculated. Mutual interaction leads to pK' displacements of 0.31 unit; which indicates a distance of approximately 7 angstrom between the two interacting histidine rings according to the model of Tanford and Roxby. The proton resonances of the two interacting histidines are doubled in the pH region 6.7-7.0 suggesting the presence of two forms of the enzyme having lifetimes in excess of 30 msec."}
{"id": "PMID:235950", "title": "Electrostatic effects in myoglobin. Application of the modified Tanford-Kirkwood theory to myoglobins from horse, California grey whale, harbor seal, and California sea lion.", "content": "The modified Tanford-Kirkwood electrostatic theory (Shire et al., 1974a) was applied to ferrimyoglobins from the following animal species: sperm whale (Physeter catodon), horse, California grey whale (Eschrichtius gibbosus), harbor seal (Phoca vitulina), and California sea lion (Zalophus californianus). Computations were made of the overall hydrogen ion titration curves of the proteins, and of pH and ionic strength variations of ionization equilibria for individual groups in the protein, with particular reference to the hemic acid ionization of the iron bound water molecule. Coordinates and static solvent accessibility were estimated in terms of the sperm whale myoglobin structure. Where possible, theoretical results and experimental data are compared. Some comparative features of charge and ionization properties among the various myoglobins are presented.", "contents": "Electrostatic effects in myoglobin. Application of the modified Tanford-Kirkwood theory to myoglobins from horse, California grey whale, harbor seal, and California sea lion. The modified Tanford-Kirkwood electrostatic theory (Shire et al., 1974a) was applied to ferrimyoglobins from the following animal species: sperm whale (Physeter catodon), horse, California grey whale (Eschrichtius gibbosus), harbor seal (Phoca vitulina), and California sea lion (Zalophus californianus). Computations were made of the overall hydrogen ion titration curves of the proteins, and of pH and ionic strength variations of ionization equilibria for individual groups in the protein, with particular reference to the hemic acid ionization of the iron bound water molecule. Coordinates and static solvent accessibility were estimated in terms of the sperm whale myoglobin structure. Where possible, theoretical results and experimental data are compared. Some comparative features of charge and ionization properties among the various myoglobins are presented."}
{"id": "PMID:235951", "title": "Acetylation of ribosome-associated proteins in vitro by an acetyltransferanse bound to rat liver ribosomes.", "content": "Incubation of rat liver ribosomes with [1-14-C]acetyl-coenzyme A results in the incorporation of [14-C]acetyl into a material insoluble in cold trichloroacetic acid. The acetyltransferase involved in the self-acetylation of ribosomes can be released by high salt washing of the ribosomes; the activity of the solubilized enzyme can be assayed using histones as acetyl acceptors. Electrophoretic analysis of acetylated risosomes or ribosomal proteins indicated that the acetyl radicals are associated with a group of relatively basic proteins, having molecular weights ranging from 10,000 to 45,000. Chromatographic analysis of the enzymatic hydrolsates of proteins extracted from acetylated ribosomes indicates that acetylation is mainly or exclusively NH2 terminal. Almost 80% of the acetyl proteins are released from the ribosomes by high salt treatment. Most of the acetyl radicals not solubilized by the high salt treatment were found in the 60S subunit, associated with a protein(s) having an apparent molecular weight of 43,000. This acetyl protein(s) was released from the 60S subunit by EDTA treatment and was found in a ribonucleoprotein complex having a bouyant density of 1.56.", "contents": "Acetylation of ribosome-associated proteins in vitro by an acetyltransferanse bound to rat liver ribosomes. Incubation of rat liver ribosomes with [1-14-C]acetyl-coenzyme A results in the incorporation of [14-C]acetyl into a material insoluble in cold trichloroacetic acid. The acetyltransferase involved in the self-acetylation of ribosomes can be released by high salt washing of the ribosomes; the activity of the solubilized enzyme can be assayed using histones as acetyl acceptors. Electrophoretic analysis of acetylated risosomes or ribosomal proteins indicated that the acetyl radicals are associated with a group of relatively basic proteins, having molecular weights ranging from 10,000 to 45,000. Chromatographic analysis of the enzymatic hydrolsates of proteins extracted from acetylated ribosomes indicates that acetylation is mainly or exclusively NH2 terminal. Almost 80% of the acetyl proteins are released from the ribosomes by high salt treatment. Most of the acetyl radicals not solubilized by the high salt treatment were found in the 60S subunit, associated with a protein(s) having an apparent molecular weight of 43,000. This acetyl protein(s) was released from the 60S subunit by EDTA treatment and was found in a ribonucleoprotein complex having a bouyant density of 1.56."}
{"id": "PMID:235952", "title": "Magnetic circular dichroic spectra of cobalt(II) substituted metalloenzymes.", "content": "The magnetic circular dichroic (MCD) spectra of cobalt(II) sugstituted metalloenzymes have been studied and compared to a series of four-, five-, and six-coordinate cobalt(II) model complexes previously examined (T. A. Kaden et al. (1974), Inorg. Chem. 13, 2582). The MCD spectra of cobalt substituted carboxypeptidase A, procarboxypeptidase ta, and thermolysin are consistent with earlier deductions of tetrahedral coordination from absorption spectra and also with X-ray structure analysis. Inhibitors fail to alter their MCD spectra significantly. The MCD spectra of cobalt alkaline phosphatase and carbonic anhydrase are more complex and their pH dependence and alteration by inhibitors are  discussed in terms of known cobalt(II) models.", "contents": "Magnetic circular dichroic spectra of cobalt(II) substituted metalloenzymes. The magnetic circular dichroic (MCD) spectra of cobalt(II) sugstituted metalloenzymes have been studied and compared to a series of four-, five-, and six-coordinate cobalt(II) model complexes previously examined (T. A. Kaden et al. (1974), Inorg. Chem. 13, 2582). The MCD spectra of cobalt substituted carboxypeptidase A, procarboxypeptidase ta, and thermolysin are consistent with earlier deductions of tetrahedral coordination from absorption spectra and also with X-ray structure analysis. Inhibitors fail to alter their MCD spectra significantly. The MCD spectra of cobalt alkaline phosphatase and carbonic anhydrase are more complex and their pH dependence and alteration by inhibitors are  discussed in terms of known cobalt(II) models."}
{"id": "PMID:235953", "title": "Characterization of a ribonuclease from bovine brain.", "content": "An alkaline ribonuclease (pH optimum near 8) has been purified from whole beef brains and found to have a base specificity like that of bovine pancreatic ribonuclease, but in most other respects to be distinguishable from the enzymes of bovine pancreas, semen, or brain nuclei. The preparation appears homogeneous in sedimentation equilibrium and probably so in polyacrylamide gel electrophoresis under normal or dissociating conditions. Sedimentation equilibrium and SDS gel electrophoresis both indicate a molecular weight of 2.4-2.6 times 10-4, and tryptic and chymotrypic peptide patterns are consistent with a protein of this size. No dissociation into subunits has been attained. The enzyme is not precipitated by antiserum to pancreatic ribonuclease, although its activity is inhibited by this antiserum with low efficiency. In comparisons of the hydrolysis of RNA the brain enzyme was found to have a similar specificity to pancreatic RNase, but to have a loser Km for RNA and to produce significantly different oligonucleotides upon partial hydrolysis of bacteriophage RNA, suggesting differences in the mechanism of substrate recognition. In contrast, nuclease inactivation by iodoacetate at pH 5.5 is indistinguishable for pancreatic or purified brain RNase.", "contents": "Characterization of a ribonuclease from bovine brain. An alkaline ribonuclease (pH optimum near 8) has been purified from whole beef brains and found to have a base specificity like that of bovine pancreatic ribonuclease, but in most other respects to be distinguishable from the enzymes of bovine pancreas, semen, or brain nuclei. The preparation appears homogeneous in sedimentation equilibrium and probably so in polyacrylamide gel electrophoresis under normal or dissociating conditions. Sedimentation equilibrium and SDS gel electrophoresis both indicate a molecular weight of 2.4-2.6 times 10-4, and tryptic and chymotrypic peptide patterns are consistent with a protein of this size. No dissociation into subunits has been attained. The enzyme is not precipitated by antiserum to pancreatic ribonuclease, although its activity is inhibited by this antiserum with low efficiency. In comparisons of the hydrolysis of RNA the brain enzyme was found to have a similar specificity to pancreatic RNase, but to have a loser Km for RNA and to produce significantly different oligonucleotides upon partial hydrolysis of bacteriophage RNA, suggesting differences in the mechanism of substrate recognition. In contrast, nuclease inactivation by iodoacetate at pH 5.5 is indistinguishable for pancreatic or purified brain RNase."}
{"id": "PMID:235954", "title": "Synthesis and enzymic activity of 8-acyl and 8-alkyl derivatives of guanosine 3, 5-cyclic phosphate.", "content": "Several new 8-alkyl and 8-acyl derivatives of quanosie 3',5'-cyclic phosphate (cGMP) and inosine 3',5'-cyclic phosphate (cGMP) were prepared by direct alkylation or acylation of the parent cyclic nucleotide via free radicals generated in situ. These compounds have been examined for their ability to stimulate a cGMP-dependent protein kinase, and several of the cGMP derivatives were as active in this regard as cGMP. These compounds proved to be quite ineffective when tested for their ability to activate an adenosine 3',5'-cyclic phosphate (cAMP) dependent protein kinase. In addition, these 8-substituted cGMP derivatives are not substrates for a phosphodiesterase preparation from rabbit kidney, but do show inhibition of the hydrolysis of cAMP by crude phosphodiesterase preparations from rabbit lung and beef heart.", "contents": "Synthesis and enzymic activity of 8-acyl and 8-alkyl derivatives of guanosine 3, 5-cyclic phosphate. Several new 8-alkyl and 8-acyl derivatives of quanosie 3',5'-cyclic phosphate (cGMP) and inosine 3',5'-cyclic phosphate (cGMP) were prepared by direct alkylation or acylation of the parent cyclic nucleotide via free radicals generated in situ. These compounds have been examined for their ability to stimulate a cGMP-dependent protein kinase, and several of the cGMP derivatives were as active in this regard as cGMP. These compounds proved to be quite ineffective when tested for their ability to activate an adenosine 3',5'-cyclic phosphate (cAMP) dependent protein kinase. In addition, these 8-substituted cGMP derivatives are not substrates for a phosphodiesterase preparation from rabbit kidney, but do show inhibition of the hydrolysis of cAMP by crude phosphodiesterase preparations from rabbit lung and beef heart."}
{"id": "PMID:235955", "title": "Chloride flux in bilayer membranes: chloride permeability in aqueous dispersions of single-walled, bilayer vesicles.", "content": "Aqueous dispersions of phosphatidylcholine vesicles were utilized to determine bilayer permeability to 36-Cl as a function of pH and temperature. These dispersions were comprised of single-walled vesicles, homogeneous in size, prepared by sonication of purified egg phosphatidylcholine under argon followed by fractionation on a molecular sieve. Permeability constants calculated from the inward flux of 36-Cl and the geometric parameters of these vesicles proved to be dependent on both pH and temperature. Analysis of these dependences leads to the conclusion that 36-Cl permeation in the presence of KCl is due principally to a carrier mediated exchange process involving a phospholipid-HCL complex. Net permeation by H-36-Cl may make a small contribution to the 36-Cl flux, however, studies carried out at very low chloride concentrations show that this flux is much smaller than the exchange flux. Thus chloride permeability for the exchange process is 1.5 times 10- minus 11 cmsec- minus 1 while the corresponding coefficient for the net flux of H-36-Cl is 1.0 times 10- minus 12 cm sec- minus 1 at pH 7. The activation energy for the 36-Cl exchange flux was found to be 19 plus or minus 2 kcal/mol. This value is similar to that obtained for the transbilayer \"flip-flop\" of phosphatidylcholine molecules in a similar system (Kornberg and McConnell, 1971). This correspondence together with the fact that the experimentally determined flux of 36-Cl agrees well with that calculated from the \"flip-flop\" parameters, strongly suggests that the flux of 36-Cl and \"flip-flop\" of phosphatidylcholine may be the same process.", "contents": "Chloride flux in bilayer membranes: chloride permeability in aqueous dispersions of single-walled, bilayer vesicles. Aqueous dispersions of phosphatidylcholine vesicles were utilized to determine bilayer permeability to 36-Cl as a function of pH and temperature. These dispersions were comprised of single-walled vesicles, homogeneous in size, prepared by sonication of purified egg phosphatidylcholine under argon followed by fractionation on a molecular sieve. Permeability constants calculated from the inward flux of 36-Cl and the geometric parameters of these vesicles proved to be dependent on both pH and temperature. Analysis of these dependences leads to the conclusion that 36-Cl permeation in the presence of KCl is due principally to a carrier mediated exchange process involving a phospholipid-HCL complex. Net permeation by H-36-Cl may make a small contribution to the 36-Cl flux, however, studies carried out at very low chloride concentrations show that this flux is much smaller than the exchange flux. Thus chloride permeability for the exchange process is 1.5 times 10- minus 11 cmsec- minus 1 while the corresponding coefficient for the net flux of H-36-Cl is 1.0 times 10- minus 12 cm sec- minus 1 at pH 7. The activation energy for the 36-Cl exchange flux was found to be 19 plus or minus 2 kcal/mol. This value is similar to that obtained for the transbilayer \"flip-flop\" of phosphatidylcholine molecules in a similar system (Kornberg and McConnell, 1971). This correspondence together with the fact that the experimentally determined flux of 36-Cl agrees well with that calculated from the \"flip-flop\" parameters, strongly suggests that the flux of 36-Cl and \"flip-flop\" of phosphatidylcholine may be the same process."}
{"id": "PMID:235956", "title": "Polyacrylamide gels copolymerized with active esters. A new medium for affinity systems.", "content": "A new and versatile method for linking biologically active ligands to a polyacrylamide matrix is reported. Active esters of acrylic acid (N-succinimicyl acrylate and N-phthalimidyl acrylate) were synthesized, then copolymerized with acrylamide and N,N'-methylenebisacrylamide. Displacement of the active ester in the gel thus formed by various ligands containing aliphatic amino groups resulted in the formation of stable amid bonds between the ligands and the polyacrylamide gel. The affinity gel thus prepared has the following advantages: (i) resistance to chemical and microbiological degradation, (ii) ease of control of ligand level and higher levels of ligand possible, (iii) ease of control of porosity, and (iv) total displacement of the active ester under suitable conditions. Efficacy of this system was tested by preparation of 6-aminohexyl 2-acetamido-2-deoxy-beta-D-glucopyranoside derivative polyacrylamide gel by the described method. It was found to be more effective for purification of wheat germ agglutinin than the previously published affinity chromatography systems and the wheat germ hemagglutinin was obtained in crystalline form. In addition, partial resolution of isolectins was obtained from the affinity gel witha pH gradient.", "contents": "Polyacrylamide gels copolymerized with active esters. A new medium for affinity systems. A new and versatile method for linking biologically active ligands to a polyacrylamide matrix is reported. Active esters of acrylic acid (N-succinimicyl acrylate and N-phthalimidyl acrylate) were synthesized, then copolymerized with acrylamide and N,N'-methylenebisacrylamide. Displacement of the active ester in the gel thus formed by various ligands containing aliphatic amino groups resulted in the formation of stable amid bonds between the ligands and the polyacrylamide gel. The affinity gel thus prepared has the following advantages: (i) resistance to chemical and microbiological degradation, (ii) ease of control of ligand level and higher levels of ligand possible, (iii) ease of control of porosity, and (iv) total displacement of the active ester under suitable conditions. Efficacy of this system was tested by preparation of 6-aminohexyl 2-acetamido-2-deoxy-beta-D-glucopyranoside derivative polyacrylamide gel by the described method. It was found to be more effective for purification of wheat germ agglutinin than the previously published affinity chromatography systems and the wheat germ hemagglutinin was obtained in crystalline form. In addition, partial resolution of isolectins was obtained from the affinity gel witha pH gradient."}
{"id": "PMID:235957", "title": "An acid induced conformational transition of denatured cytochrome c in urea and guanidine hydrochloride solutions.", "content": "Previous work has shown that at neutral pH ferricytochrome c (horse heart) retains certain residual structures in concentrated solutions of urea or guanidine hydrochloride (Tsong, T. Y. (1974), J. Biol. Chem. 249, 1988). Present studies reveal that cooperative unfolding of these residual structures can be achieved by acidification of the protein to pH 4 in 9 M urea but can only be partially achieved in a 6 M guanidine hydrochloride solution. The evidence that the residual structures unfold in 9 M urea upon acidification is twofold. (1) Further uncoupling of the Trp-59-heme interaction occurs; this is reflected in the intensification of the tryptophan fluorescence from 55 to 90 percent relative to that of free tryptophan in the same solvent. (2) The intrinsic viscosity of the protein solution increases from 15.0 to 21 ml/g. The acidification also induces a spin-state transformation of the heme group at pH 5 both in urea and in guanidine hydrochloride. Acidic titration of the protein in urea and guanidine hydrochloride indicates that the unfolding involves the absorption of a single proton. However, the kinetics of the spin-state transformation are triphasic. These results suggest that the displacement of the ligand His-18 by a solvent molecule and the subsequent disintegration of the residual structures are complex processes and involve at least three kinetic steps. The ineffectiveness of guanidine hydrochloride as a denaturant for ferricytochrome c is shown to be due to the presence of the high concentration of Cl minus which can stabilize certain elements of the protein structure.", "contents": "An acid induced conformational transition of denatured cytochrome c in urea and guanidine hydrochloride solutions. Previous work has shown that at neutral pH ferricytochrome c (horse heart) retains certain residual structures in concentrated solutions of urea or guanidine hydrochloride (Tsong, T. Y. (1974), J. Biol. Chem. 249, 1988). Present studies reveal that cooperative unfolding of these residual structures can be achieved by acidification of the protein to pH 4 in 9 M urea but can only be partially achieved in a 6 M guanidine hydrochloride solution. The evidence that the residual structures unfold in 9 M urea upon acidification is twofold. (1) Further uncoupling of the Trp-59-heme interaction occurs; this is reflected in the intensification of the tryptophan fluorescence from 55 to 90 percent relative to that of free tryptophan in the same solvent. (2) The intrinsic viscosity of the protein solution increases from 15.0 to 21 ml/g. The acidification also induces a spin-state transformation of the heme group at pH 5 both in urea and in guanidine hydrochloride. Acidic titration of the protein in urea and guanidine hydrochloride indicates that the unfolding involves the absorption of a single proton. However, the kinetics of the spin-state transformation are triphasic. These results suggest that the displacement of the ligand His-18 by a solvent molecule and the subsequent disintegration of the residual structures are complex processes and involve at least three kinetic steps. The ineffectiveness of guanidine hydrochloride as a denaturant for ferricytochrome c is shown to be due to the presence of the high concentration of Cl minus which can stabilize certain elements of the protein structure."}
{"id": "PMID:235958", "title": "Kinetic studies on the five principal components of normal adult human hemoglobin.", "content": "The five principal components of human hemoglobin (Ala, Alb, Alc, Ao, and A2) have been isolated by column chromatography and by preparative isoelectric focusing in gels. The isoelectric points and a number of kinetic parameters have been determined for each hemoglobin. The greatest kinetic differences are found in the binding of CO to the deoxy conformation. At pH 7, A0 and A2 are nearly identical in their overall reaction with CO, whereas the initial lag phase characteristic of crude hemolysate and A0 is greatly reduced in Ala and Alc and is essentially absent in Alb. The general effect of p-mercuribenzoate bindind on CO association is to magnify kinetic differences among the hemoglobins, diminish the initial lag phase, and increase the overall rate of CO binding. Hemoglobin Ala is anomalous in that the overall CO binding rate actually decreases after reaction with the mercurial. In terms of an Adair model with four association constants the rate constant for the binding of the first molecule of CO (1l') showed the greatest variation among the five hemoglobins, with A0 having the smallest constant, and Alb the largest. For the native hemoglobins, 1l' for Alb was more than twice that for A0; for the mercurated hemoglobins, the difference was greater than threefold. Raising the pH form 7 to 8 increases 1l' for all hemoglobins, but Ala is anomalous in having a slower overall rate for CO binding at the higher pH. At pH 9, the time course of CO binding is biphasic for all hemoglobins, with A0, the fastest, and Ala, the slowest, differing by nearly threefold in rate. The equilibrium constant for the tetramer-dimer equilibrium was determined by flash photolysis. The largest dissociation constant occurs for Ala and is 4.4 times that for A0, and 5.6 times that for Alc, the least dissociated of the hemoglobins. The overall oxygen dissociation reaction is biphasic for Ala and Alb, with the two phases differing by a factor of 5; the dissociation reactions for the other three hemoglobins appear essentially monophasic. The kinetics of dissociation of the first oxygen molecule from oxyhemoglobin are very similar for all five hemoglobins, as are the association kinetics for CN-minus and N3-minus binding to the five methemoglobins.", "contents": "Kinetic studies on the five principal components of normal adult human hemoglobin. The five principal components of human hemoglobin (Ala, Alb, Alc, Ao, and A2) have been isolated by column chromatography and by preparative isoelectric focusing in gels. The isoelectric points and a number of kinetic parameters have been determined for each hemoglobin. The greatest kinetic differences are found in the binding of CO to the deoxy conformation. At pH 7, A0 and A2 are nearly identical in their overall reaction with CO, whereas the initial lag phase characteristic of crude hemolysate and A0 is greatly reduced in Ala and Alc and is essentially absent in Alb. The general effect of p-mercuribenzoate bindind on CO association is to magnify kinetic differences among the hemoglobins, diminish the initial lag phase, and increase the overall rate of CO binding. Hemoglobin Ala is anomalous in that the overall CO binding rate actually decreases after reaction with the mercurial. In terms of an Adair model with four association constants the rate constant for the binding of the first molecule of CO (1l') showed the greatest variation among the five hemoglobins, with A0 having the smallest constant, and Alb the largest. For the native hemoglobins, 1l' for Alb was more than twice that for A0; for the mercurated hemoglobins, the difference was greater than threefold. Raising the pH form 7 to 8 increases 1l' for all hemoglobins, but Ala is anomalous in having a slower overall rate for CO binding at the higher pH. At pH 9, the time course of CO binding is biphasic for all hemoglobins, with A0, the fastest, and Ala, the slowest, differing by nearly threefold in rate. The equilibrium constant for the tetramer-dimer equilibrium was determined by flash photolysis. The largest dissociation constant occurs for Ala and is 4.4 times that for A0, and 5.6 times that for Alc, the least dissociated of the hemoglobins. The overall oxygen dissociation reaction is biphasic for Ala and Alb, with the two phases differing by a factor of 5; the dissociation reactions for the other three hemoglobins appear essentially monophasic. The kinetics of dissociation of the first oxygen molecule from oxyhemoglobin are very similar for all five hemoglobins, as are the association kinetics for CN-minus and N3-minus binding to the five methemoglobins."}
{"id": "PMID:235959", "title": "Sulfhydryl groups in hemoglobin. A new molecular probe at the alpha1 beta 1 interface studied by Fourier transform infrared spectroscopy.", "content": "Infrared absorption bands due to sulfhydryl groups (VSH) of alpha-104(G11) and beta-112 (G14) cysteine residues of human carboxyhemoglobin (HbCO) have been observed near 2560 cm- minus 1 by use of Fourier transform infrared (FTIR) spectroscopy. The beta-93 cysteine SH groups absorb infrared radiation so weakly that they are not distinguished from background. Only single SH absorption bands due to the alpha-104 cysteines of pig and horse hemoglobin are observed. The SH absorption bands from human HbCO disappear in alkali, are broadened by detergent or guanidinium chloride, and show a complex titration curve, and an isotopic frequency shift (VSD/VSH equals to 0.7267) virtually identical with that reported for methanethiol. The integrated absorption coefficient (epsilonmM(area)) for 0.1 M ethanetiol increased with H-bond acceptor solvents in the order: CCl4 (0.07), water (0.21), acetone (0.43), and N,N-dimethyl-acetamide (1.35 mM- minus 1 cm- minus 2). Comparison of the integrated absorption coefficients for the alpha-104 cysteine SH (2.43), and the beta-112 SH (0.80), of human HbCO with those of ethanetiol solutions suggested specifically H-bonded structures with peptide carbonyl groups 4 (or 3) residues back in the G helices. This was found to agree with a molecular model of the alpha-chain G helix of horse HbO2 built to coordinates from M. F. Perutz.", "contents": "Sulfhydryl groups in hemoglobin. A new molecular probe at the alpha1 beta 1 interface studied by Fourier transform infrared spectroscopy. Infrared absorption bands due to sulfhydryl groups (VSH) of alpha-104(G11) and beta-112 (G14) cysteine residues of human carboxyhemoglobin (HbCO) have been observed near 2560 cm- minus 1 by use of Fourier transform infrared (FTIR) spectroscopy. The beta-93 cysteine SH groups absorb infrared radiation so weakly that they are not distinguished from background. Only single SH absorption bands due to the alpha-104 cysteines of pig and horse hemoglobin are observed. The SH absorption bands from human HbCO disappear in alkali, are broadened by detergent or guanidinium chloride, and show a complex titration curve, and an isotopic frequency shift (VSD/VSH equals to 0.7267) virtually identical with that reported for methanethiol. The integrated absorption coefficient (epsilonmM(area)) for 0.1 M ethanetiol increased with H-bond acceptor solvents in the order: CCl4 (0.07), water (0.21), acetone (0.43), and N,N-dimethyl-acetamide (1.35 mM- minus 1 cm- minus 2). Comparison of the integrated absorption coefficients for the alpha-104 cysteine SH (2.43), and the beta-112 SH (0.80), of human HbCO with those of ethanetiol solutions suggested specifically H-bonded structures with peptide carbonyl groups 4 (or 3) residues back in the G helices. This was found to agree with a molecular model of the alpha-chain G helix of horse HbO2 built to coordinates from M. F. Perutz."}
{"id": "PMID:235960", "title": "Equilibrium and kinetics of the reaction of Aplysia myoglobin with azide.", "content": "The present paper reports a study on the equilibria and kinetics of the acid-alkaline transition and the azide binding reaction by ferric Aplysia myoglobin. A single completely reversible spectrophotometric titration curve is found over the pH range from similar to 5 to similar to 9, with an apparent pK equals to 7.5 for the acid-alkaline transition. The kinetics of the process, followed by the temperature-jump method, gives, at pH values close to the pK of the transition, one single, well-resolved, relaxation independent of protein concentration and of type of buffer used. The pattern accords to a simple pH dependent reaction, in buffered medium, between the two forms of the protein. The results of the azide binding reaction show that the process conforms to simple equilibrium as expected for a single site protein. The m\u00e9asured association constant is reported as a function of pH. The kinetics of the reaction of Aplysia metMb with N3- minus shows, on the other hand, a complex behavior. The relaxation pattern is found to strongly depend on pH and ligand concentration in such a way to suggest a linkage between ligand binding and acid-alkaline transition. The system is discussed on the basis of two simplifying conditions, i.e., at low and higher pH with respect to the pK of the acid-alkaline transition. At acid pH the reaction corresponds to a single bimolecular process as expected for a simple binding reaction; at alkaline pH, the dependence of relaxation time on ligand concentration implies the existence of a rate-limiting monomolecular step. On the basis of a reaction scheme implying that binding of the ligand can only occur through the acid (aquomet) form of the protein via the displacement of the water molecule, the experimental data are quantitatively accounted for.", "contents": "Equilibrium and kinetics of the reaction of Aplysia myoglobin with azide. The present paper reports a study on the equilibria and kinetics of the acid-alkaline transition and the azide binding reaction by ferric Aplysia myoglobin. A single completely reversible spectrophotometric titration curve is found over the pH range from similar to 5 to similar to 9, with an apparent pK equals to 7.5 for the acid-alkaline transition. The kinetics of the process, followed by the temperature-jump method, gives, at pH values close to the pK of the transition, one single, well-resolved, relaxation independent of protein concentration and of type of buffer used. The pattern accords to a simple pH dependent reaction, in buffered medium, between the two forms of the protein. The results of the azide binding reaction show that the process conforms to simple equilibrium as expected for a single site protein. The m\u00e9asured association constant is reported as a function of pH. The kinetics of the reaction of Aplysia metMb with N3- minus shows, on the other hand, a complex behavior. The relaxation pattern is found to strongly depend on pH and ligand concentration in such a way to suggest a linkage between ligand binding and acid-alkaline transition. The system is discussed on the basis of two simplifying conditions, i.e., at low and higher pH with respect to the pK of the acid-alkaline transition. At acid pH the reaction corresponds to a single bimolecular process as expected for a simple binding reaction; at alkaline pH, the dependence of relaxation time on ligand concentration implies the existence of a rate-limiting monomolecular step. On the basis of a reaction scheme implying that binding of the ligand can only occur through the acid (aquomet) form of the protein via the displacement of the water molecule, the experimental data are quantitatively accounted for."}
{"id": "PMID:235961", "title": "L-phenylalanine ammonia-lyase (maize, potato, and Rhodotorula glutinis). Studies of the prosthetic group with nitromethane.", "content": "Highly purified enzyme (EC 4.1.3.5) from Rhodotorula glutinis was shown by sodium dodecyl sulfate gel electrophoresis to have subunits which if not identical are closely similar in molecular weight. Like the enzyme from maize and potato [Havir, E. A., and Hanson, K. R. (1973), Biochemistry 12, 1583] it is a tetramer of molecular weight similar to 4 times 83,000. Enzyme from all three sources inactivated and labeled at the active site with 14-CH3NO2 gave on HCl hydrolysis 14-CO2, H-14-CO2H, D- and L-[14-C]aspartic acid, and unidentified radioactive products. In addition, the labeled R. glutinis enzyme gave [1,2-14-C2]glycine. The formation of the first three products is compatible with the hypothesis that the electrophilic prosthetic group of the enzyme contains the dehydroalanine imine system greater than C equals to N minus C-alpha(equals to C-beta-H2)COminus and inactivation involves attack on C-beta. The second-order rate constants for CH3NO2 inactivation varied with pH as a simple titration curve. The pKa values calculated from the curves for the three enzymes differed and were lower than the pKa of CH3NO2 by at least 1 pH unit. Apparently the inactivation process is enzyme catalyzed. Both inactivation and addition of the substrate amino group may occur with attack on C-beta.", "contents": "L-phenylalanine ammonia-lyase (maize, potato, and Rhodotorula glutinis). Studies of the prosthetic group with nitromethane. Highly purified enzyme (EC 4.1.3.5) from Rhodotorula glutinis was shown by sodium dodecyl sulfate gel electrophoresis to have subunits which if not identical are closely similar in molecular weight. Like the enzyme from maize and potato [Havir, E. A., and Hanson, K. R. (1973), Biochemistry 12, 1583] it is a tetramer of molecular weight similar to 4 times 83,000. Enzyme from all three sources inactivated and labeled at the active site with 14-CH3NO2 gave on HCl hydrolysis 14-CO2, H-14-CO2H, D- and L-[14-C]aspartic acid, and unidentified radioactive products. In addition, the labeled R. glutinis enzyme gave [1,2-14-C2]glycine. The formation of the first three products is compatible with the hypothesis that the electrophilic prosthetic group of the enzyme contains the dehydroalanine imine system greater than C equals to N minus C-alpha(equals to C-beta-H2)COminus and inactivation involves attack on C-beta. The second-order rate constants for CH3NO2 inactivation varied with pH as a simple titration curve. The pKa values calculated from the curves for the three enzymes differed and were lower than the pKa of CH3NO2 by at least 1 pH unit. Apparently the inactivation process is enzyme catalyzed. Both inactivation and addition of the substrate amino group may occur with attack on C-beta."}
{"id": "PMID:235962", "title": "Acid-volatile selenium formation catalyzed by glutathione reductase.", "content": "The production of acid-volatile selenide (apparently H2Se) was catalyzed by glutathione reductase in an anaerobic system containing 20 mM glutathione, 0.05 mM sodium selenite, a TPNH-generating system, and microgram quantities of highly purified yeast glutathione reductase. H2Se production in this system was proportional to glutathione reductase concentration and was maximal at pH 7. Significant nonenzymic H2Se production occurred in the system lacking glutathione reductase and TNPH. A concentration of arsenite (0.1 mM) which does not inhibit glutathione reductase inhibited selenide volatilization, as did bovine serum albumin (1.67 mg/ml). Both appear to inhibit Se volatilization by reacting with the selenide product(s). The selenotrisulfide derivative of glutathione (GSSeSG) was readily converted to H2Se by glutathione reductase and TPNH without the addition of glutathione. These results suggest that GSSeSG formed nonenzymically from glutathione and selenic undergoes stepwise reduction by glutathione reductase (or excess GSH) to GSSeH and finally to H2Se. The same pathway operates when glutathione is used as the reducing agent but to a lesser extent.", "contents": "Acid-volatile selenium formation catalyzed by glutathione reductase. The production of acid-volatile selenide (apparently H2Se) was catalyzed by glutathione reductase in an anaerobic system containing 20 mM glutathione, 0.05 mM sodium selenite, a TPNH-generating system, and microgram quantities of highly purified yeast glutathione reductase. H2Se production in this system was proportional to glutathione reductase concentration and was maximal at pH 7. Significant nonenzymic H2Se production occurred in the system lacking glutathione reductase and TNPH. A concentration of arsenite (0.1 mM) which does not inhibit glutathione reductase inhibited selenide volatilization, as did bovine serum albumin (1.67 mg/ml). Both appear to inhibit Se volatilization by reacting with the selenide product(s). The selenotrisulfide derivative of glutathione (GSSeSG) was readily converted to H2Se by glutathione reductase and TPNH without the addition of glutathione. These results suggest that GSSeSG formed nonenzymically from glutathione and selenic undergoes stepwise reduction by glutathione reductase (or excess GSH) to GSSeH and finally to H2Se. The same pathway operates when glutathione is used as the reducing agent but to a lesser extent."}
{"id": "PMID:235963", "title": "Terbium as a fluorescent probe for DNA and chromatin.", "content": "Terbium reacted with DNA and chromatin to form a complex in which terbium acted as a sensitive fluorescent probe. By measuring the narrow-line emission of Tb-3+ when DNA is selectively excited, the relative amount of Tb-3+ bound to the DNA can be calculated. Terbium was bound to DNA until one Tb-3+ was present for each phosphate group. After this point no more terbium was bound. TbCl3 was bound to chromatin in a linear manner until approximately 0.48 TbCl3 was added for each phosphate group in the chromatin-DNA solution. From these data it appears that 52% of the phosphate groups in chromatin were unavailable for binding. The binding of Tb-3+ to DNA can be reversed by prolonged dialysis against 0.5 M NaCl and chelating agents. The terbium ion is ideal in that it binds DNA tight enough so that completion of the reaction can be assumed but loose enough so that it can be removed by gentle means. Low concentrations of salt (up to 2 mM NaCl) enhance the quantum efficiency. Below pH 3 and above pH 7 the DNA-terbium complex will not form. Between pH 3 and pH 7 the quantum efficiency of the DNA terbium complex increases from either pH to a maximum at pH 5.5 to 5.6. Several biochemical uses for Tb-3+ ion are suggested.", "contents": "Terbium as a fluorescent probe for DNA and chromatin. Terbium reacted with DNA and chromatin to form a complex in which terbium acted as a sensitive fluorescent probe. By measuring the narrow-line emission of Tb-3+ when DNA is selectively excited, the relative amount of Tb-3+ bound to the DNA can be calculated. Terbium was bound to DNA until one Tb-3+ was present for each phosphate group. After this point no more terbium was bound. TbCl3 was bound to chromatin in a linear manner until approximately 0.48 TbCl3 was added for each phosphate group in the chromatin-DNA solution. From these data it appears that 52% of the phosphate groups in chromatin were unavailable for binding. The binding of Tb-3+ to DNA can be reversed by prolonged dialysis against 0.5 M NaCl and chelating agents. The terbium ion is ideal in that it binds DNA tight enough so that completion of the reaction can be assumed but loose enough so that it can be removed by gentle means. Low concentrations of salt (up to 2 mM NaCl) enhance the quantum efficiency. Below pH 3 and above pH 7 the DNA-terbium complex will not form. Between pH 3 and pH 7 the quantum efficiency of the DNA terbium complex increases from either pH to a maximum at pH 5.5 to 5.6. Several biochemical uses for Tb-3+ ion are suggested."}
{"id": "PMID:235964", "title": "Interaction of effecting ligands with lac repressor and repressor-operator complex.", "content": "The equilibrium association constants for the binding of a wide variety of effecting ligands of the lac repressor were measured by equilibrium dialysis. Also, detailed investigations of the apparent rate of dissociation of repressor-operator comples as a function of ligand concentration were carried out for several inducers and anti-inducers. The affinity of repressor-ligand comples for operator DNA was evaluated from the specific rate constants at saturating concentrations of effecting ligand. By fitting the experimental data depicting the functional dependence of the rate of dissociation upon ligand concentrations to calculated curves, assuming simple models of the induction mechanism, the equilibrium association constant for the binding of effecting ligand to repressor-operator comples was determined. Inducers reduce the affinity of lac repressor for operator DNA by a factor of approximately 1000 under standard conditions; the extent of destabilization depends on Mg2+ ion concentration. Anti-inducers increase the affinity of repressor for operator at most a factor of five. Only one neutral ligand, which binds to repressor without altering the stability of repressor-operator comples, was found. No homotropic or heterotropic interactions in the binding of effecting ligands either to repressor or to repressor-operator complex are evident.", "contents": "Interaction of effecting ligands with lac repressor and repressor-operator complex. The equilibrium association constants for the binding of a wide variety of effecting ligands of the lac repressor were measured by equilibrium dialysis. Also, detailed investigations of the apparent rate of dissociation of repressor-operator comples as a function of ligand concentration were carried out for several inducers and anti-inducers. The affinity of repressor-ligand comples for operator DNA was evaluated from the specific rate constants at saturating concentrations of effecting ligand. By fitting the experimental data depicting the functional dependence of the rate of dissociation upon ligand concentrations to calculated curves, assuming simple models of the induction mechanism, the equilibrium association constant for the binding of effecting ligand to repressor-operator comples was determined. Inducers reduce the affinity of lac repressor for operator DNA by a factor of approximately 1000 under standard conditions; the extent of destabilization depends on Mg2+ ion concentration. Anti-inducers increase the affinity of repressor for operator at most a factor of five. Only one neutral ligand, which binds to repressor without altering the stability of repressor-operator comples, was found. No homotropic or heterotropic interactions in the binding of effecting ligands either to repressor or to repressor-operator complex are evident."}
{"id": "PMID:235965", "title": "Catabolite inactivation of biodegradative threonine dehydratase of Escherichia coli.", "content": "Incubation of Escherichia coli cells with glucose, pyruvate, and certain other metabolites led to rapid inactivation of inducible biodegradative threonine dehydratase. Analysis with several mutant strains showed that pyruvate, and not a metabolite derived from pyruvate, was capable of inactivating enzyme, and that glucose acted indirectly after being converted to pyruvate. Some other alpha-keto acids such as oxaloacetate and alpha-ketobutyrate (but not alpha-ketoglutarate) were also effective. Inactivation of threonine dehydratase by pyruvate was also observed with purified enzyme preparations. The rates of enzyme inactivation increased with increased concentrations of pyruvate and decreased with increased levels of AMP. Increasing protein concentrations lowered the rates of enzyme inactivation. Dithiothreitol had a large effect on the maximum extent of inactivation of the enzyme by pyruvate; high concentrations of AMP and DTT almost completely counteracted the effect of pyruvate. Gel filtration data showed that pyruvate influenced the oligomeric state of the enzyme by altering the association-dissociation equilibrium in favor of dissociation; the Stokes' radius of the pyruvate-inactivated enzyme was 32 A as compared to 42 A  for the untreated enzyme. Reassociation of the dissociated form of the enzyme was achieved by removal of excess free pyruvate by dialysis against buffer supplemented with AMP and DTT. Incubation of threonine dehydratase with [14-C]pyruvate revealed apparent covalent attachment of pyruvate to the enzyme. Strong protein denaturants such as guanidine, urea, and sodium dodecyl sulfate failed to release bound radioactive pyruvate; the molar ratio of firmly bound pyruvate was approximately 1 mol/150,000 g of protein. Pretreatment of the enzyme with p-chloromercuribenzoate and 5,5'-dithiobis(2-nitrobenzoate) (Nbs2) did not reduce the binding of [14-C]pyruvate suggesting no active site SH was involved in the pyruvate-enzyme linkage. Titration of active and pyruvate-inactivated enzyme with Nbs2 indicated that the loss in enzyme activity was not due to oxidation of essential sulfhydryl groups on the enzyme. Based on these data we propose that the mechanism of enzyme inactivation by pyruvate involves covalent attachment of pyruvate to the active oligomeric form of the enzyme followed by dissociation of the oligomer to yield inactive enzyme.", "contents": "Catabolite inactivation of biodegradative threonine dehydratase of Escherichia coli. Incubation of Escherichia coli cells with glucose, pyruvate, and certain other metabolites led to rapid inactivation of inducible biodegradative threonine dehydratase. Analysis with several mutant strains showed that pyruvate, and not a metabolite derived from pyruvate, was capable of inactivating enzyme, and that glucose acted indirectly after being converted to pyruvate. Some other alpha-keto acids such as oxaloacetate and alpha-ketobutyrate (but not alpha-ketoglutarate) were also effective. Inactivation of threonine dehydratase by pyruvate was also observed with purified enzyme preparations. The rates of enzyme inactivation increased with increased concentrations of pyruvate and decreased with increased levels of AMP. Increasing protein concentrations lowered the rates of enzyme inactivation. Dithiothreitol had a large effect on the maximum extent of inactivation of the enzyme by pyruvate; high concentrations of AMP and DTT almost completely counteracted the effect of pyruvate. Gel filtration data showed that pyruvate influenced the oligomeric state of the enzyme by altering the association-dissociation equilibrium in favor of dissociation; the Stokes' radius of the pyruvate-inactivated enzyme was 32 A as compared to 42 A  for the untreated enzyme. Reassociation of the dissociated form of the enzyme was achieved by removal of excess free pyruvate by dialysis against buffer supplemented with AMP and DTT. Incubation of threonine dehydratase with [14-C]pyruvate revealed apparent covalent attachment of pyruvate to the enzyme. Strong protein denaturants such as guanidine, urea, and sodium dodecyl sulfate failed to release bound radioactive pyruvate; the molar ratio of firmly bound pyruvate was approximately 1 mol/150,000 g of protein. Pretreatment of the enzyme with p-chloromercuribenzoate and 5,5'-dithiobis(2-nitrobenzoate) (Nbs2) did not reduce the binding of [14-C]pyruvate suggesting no active site SH was involved in the pyruvate-enzyme linkage. Titration of active and pyruvate-inactivated enzyme with Nbs2 indicated that the loss in enzyme activity was not due to oxidation of essential sulfhydryl groups on the enzyme. Based on these data we propose that the mechanism of enzyme inactivation by pyruvate involves covalent attachment of pyruvate to the active oligomeric form of the enzyme followed by dissociation of the oligomer to yield inactive enzyme."}
{"id": "PMID:235966", "title": "Lipid biosynthesis in sebaceous glands: regulation of the synthesis of n- and branched fatty acids by malonyl-coenzyme A decarboxylase.", "content": "Crude cell-free extracts isolated from the uropygial glands of goose catalyzed the carboxylation of propionyl-CoA but not acetyl-CoA. However, a partially purified preparation catalyzed the carboxylation of both substrates and the characteristics of this carboxylase were similar to those reported for chicken liver carboxylase. The Km and Vmax for the carboxylation of either acetyl-CoA or propionyl-CoA were 1.5 times 10- minus-5 M and 0.8 mumol per min per mg, respectively. In the crude extracts an inhibitor of the acetyl-CoA carboxylase activity was detected. The inhibitor was partially purified and identified as a protein that catalyzed the rapid decarboxylation of malonyl-CoA. This enzyme was avidin-insenitive and highly specific for malonyl-CoA with very low rates of decarboxylation for methylmalonyl-CoA and malonic acid. Vmax and Km for malonyl-CoA decarboxylation, at the pH optimum of 9.5, were 12.5 mumol per min per mg and 8 times 10- minus-4 M, respectively. The relative activities of the acetyl-CoA carboxylase and malonyl-CoA decarboxylase were about 4 mumol per min per gland and 70 mumoles per min per gland, respectively. Therefore acetyl-CoA and methylmalonyl-CoA should be the major primer and elongating agent, respectively, present in the gland. The major fatty acid formed from these precursors by the fatty acid synthetase of the gland would be 2,4,6,8-tetramethyl-decanoic acid which is known to be the major fatty acid of the gland (Buckner, J. S. and Kolattukudy, P. E. (1975), Biochemistry, following paper). Therefore it is concluded that the malonyl-CoA decarboxylase controls fatty acid synthesis in this gland.", "contents": "Lipid biosynthesis in sebaceous glands: regulation of the synthesis of n- and branched fatty acids by malonyl-coenzyme A decarboxylase. Crude cell-free extracts isolated from the uropygial glands of goose catalyzed the carboxylation of propionyl-CoA but not acetyl-CoA. However, a partially purified preparation catalyzed the carboxylation of both substrates and the characteristics of this carboxylase were similar to those reported for chicken liver carboxylase. The Km and Vmax for the carboxylation of either acetyl-CoA or propionyl-CoA were 1.5 times 10- minus-5 M and 0.8 mumol per min per mg, respectively. In the crude extracts an inhibitor of the acetyl-CoA carboxylase activity was detected. The inhibitor was partially purified and identified as a protein that catalyzed the rapid decarboxylation of malonyl-CoA. This enzyme was avidin-insenitive and highly specific for malonyl-CoA with very low rates of decarboxylation for methylmalonyl-CoA and malonic acid. Vmax and Km for malonyl-CoA decarboxylation, at the pH optimum of 9.5, were 12.5 mumol per min per mg and 8 times 10- minus-4 M, respectively. The relative activities of the acetyl-CoA carboxylase and malonyl-CoA decarboxylase were about 4 mumol per min per gland and 70 mumoles per min per gland, respectively. Therefore acetyl-CoA and methylmalonyl-CoA should be the major primer and elongating agent, respectively, present in the gland. The major fatty acid formed from these precursors by the fatty acid synthetase of the gland would be 2,4,6,8-tetramethyl-decanoic acid which is known to be the major fatty acid of the gland (Buckner, J. S. and Kolattukudy, P. E. (1975), Biochemistry, following paper). Therefore it is concluded that the malonyl-CoA decarboxylase controls fatty acid synthesis in this gland."}
{"id": "PMID:235967", "title": "Lipid biosynthesis in the sebaceous glands: synthesis of multibranched fatty acids from methylmalonyl-coenzyme A in cell-free preparations from the uropygial gland of goose.", "content": "Cell-free extracts from the uropygial gland of goose catalyzed the incorporation of malonyl-CoA and methylmalonyl-CoA into n- and multi-branched fatty acids, respectively, with NADPH as the preferred reductant. Methylmalonyl-CoA was shown to be incorporated almost exclusively into the acyl portion of wax esters by the cell-free extract while malonyl-CoA was incorporated into polar lipids and both the acyl and alcohol portions of the wax. The optimal pH for the synthesis of both n- and multibranched acids was 6.0. Apparent Km and Vmax for malonyl-CoA were 2 times 10- minus-4 M and 250 nmol per min per mg, respectively, while the Km and Vmax for methylmalonyl-CoA were 7.7 times 10- minus-4 M and 0.8 nmol per min per mg, respectively with 105,000g supernatant; but partial purification resulted in a tenfold decrease in Km values. The partially purified synthetase preparation catalyzed the formation of n-C16 acid (80%) and n-C18 acid (20%) from acetyl-CoA and malonyl-CoA. With the same synthetase preparation and the appropriate primer methylmalonyl-CoA was converted into 2,4,6,8-tetramethyldecanoic acid and 2,4,6,8-tetramethylundecanoic acid which were identified by radio gas-liquid chromatography and combined gas chromatography-mass spectrometry. Experiments with an equimolecular mixture of acetyl-CoA and propionyl-CoA showed that the synthetase preferred acetyl-CoA as a primer. Since malonyl-CoA is known to be rapidly decarboxylated in the gland, acetyl-CoA and methylmalonyl-CoA are expected to be the major primer and elongating agent, respectively, available in the gland and therefore 2,4,6,8-tetramethyldecanoic acid should be the major product. Combined gas-liquid chromatography and mass spectrometry demonstrated that this acid was in fact the major acid of the gland.", "contents": "Lipid biosynthesis in the sebaceous glands: synthesis of multibranched fatty acids from methylmalonyl-coenzyme A in cell-free preparations from the uropygial gland of goose. Cell-free extracts from the uropygial gland of goose catalyzed the incorporation of malonyl-CoA and methylmalonyl-CoA into n- and multi-branched fatty acids, respectively, with NADPH as the preferred reductant. Methylmalonyl-CoA was shown to be incorporated almost exclusively into the acyl portion of wax esters by the cell-free extract while malonyl-CoA was incorporated into polar lipids and both the acyl and alcohol portions of the wax. The optimal pH for the synthesis of both n- and multibranched acids was 6.0. Apparent Km and Vmax for malonyl-CoA were 2 times 10- minus-4 M and 250 nmol per min per mg, respectively, while the Km and Vmax for methylmalonyl-CoA were 7.7 times 10- minus-4 M and 0.8 nmol per min per mg, respectively with 105,000g supernatant; but partial purification resulted in a tenfold decrease in Km values. The partially purified synthetase preparation catalyzed the formation of n-C16 acid (80%) and n-C18 acid (20%) from acetyl-CoA and malonyl-CoA. With the same synthetase preparation and the appropriate primer methylmalonyl-CoA was converted into 2,4,6,8-tetramethyldecanoic acid and 2,4,6,8-tetramethylundecanoic acid which were identified by radio gas-liquid chromatography and combined gas chromatography-mass spectrometry. Experiments with an equimolecular mixture of acetyl-CoA and propionyl-CoA showed that the synthetase preferred acetyl-CoA as a primer. Since malonyl-CoA is known to be rapidly decarboxylated in the gland, acetyl-CoA and methylmalonyl-CoA are expected to be the major primer and elongating agent, respectively, available in the gland and therefore 2,4,6,8-tetramethyldecanoic acid should be the major product. Combined gas-liquid chromatography and mass spectrometry demonstrated that this acid was in fact the major acid of the gland."}
{"id": "PMID:235968", "title": "Conformations and interactions of histone H2A (F2A2, ALK).", "content": "Conformational changes in histone H2A (ALK, F2A2, IIbl) as a function of ionic strength and pH have been followed using high resolution nuclear magnetic resonance (NMR), circular dichroism (CD), and infrared (ir). While change in pH from 3 to 7 (no added salt) causes little structural change, added salt induces the formation of both alpha helix (28 percent maximum) and intermolecular associates in the region of the molecule between 25 and 113. No beta structure was observed at high salt. By the use of different salts it was shown that the structural changes were due largely to nonspecific counterion screening by the added anion. Comparison of observed with simulated NMR spectra has led to the proposal that an ionic strength dependent equilibrium exists between largely unstructured coil molecules and fully structured and aggregated molecules. NMR spectra of H2A obtained in the presence of DNA showed that both the N- and C-terminal regions bind to DNA, i.e., not the portion of the chain that is involved in interhistone interactions.", "contents": "Conformations and interactions of histone H2A (F2A2, ALK). Conformational changes in histone H2A (ALK, F2A2, IIbl) as a function of ionic strength and pH have been followed using high resolution nuclear magnetic resonance (NMR), circular dichroism (CD), and infrared (ir). While change in pH from 3 to 7 (no added salt) causes little structural change, added salt induces the formation of both alpha helix (28 percent maximum) and intermolecular associates in the region of the molecule between 25 and 113. No beta structure was observed at high salt. By the use of different salts it was shown that the structural changes were due largely to nonspecific counterion screening by the added anion. Comparison of observed with simulated NMR spectra has led to the proposal that an ionic strength dependent equilibrium exists between largely unstructured coil molecules and fully structured and aggregated molecules. NMR spectra of H2A obtained in the presence of DNA showed that both the N- and C-terminal regions bind to DNA, i.e., not the portion of the chain that is involved in interhistone interactions."}
{"id": "PMID:235969", "title": "Conformation and cooperativity in hemoglobin.", "content": "19-F and 31-P nuclear magnetic resonance (NMR) spectroscopy have been used to study the ligand binding process in human hemoglobin. 19-F nuclear magnetic resonance studies of hemoglobin specifically trifluoroacetonylated at cysteine-beta93 have permitted observation and characterization of molecular species containing two and three ligands. The behavior of these intermediate species in response to changes in pH and organic phosphate concentration is not completely consistent with any of the current theories of allostery. A model consistent with the 19-F and 31-P NMR data is proposed.", "contents": "Conformation and cooperativity in hemoglobin. 19-F and 31-P nuclear magnetic resonance (NMR) spectroscopy have been used to study the ligand binding process in human hemoglobin. 19-F nuclear magnetic resonance studies of hemoglobin specifically trifluoroacetonylated at cysteine-beta93 have permitted observation and characterization of molecular species containing two and three ligands. The behavior of these intermediate species in response to changes in pH and organic phosphate concentration is not completely consistent with any of the current theories of allostery. A model consistent with the 19-F and 31-P NMR data is proposed."}
{"id": "PMID:235970", "title": "Homogeneity and variability in the structure of azurin molecules studied by fluorescence decay and circular polarization.", "content": "The fluorescence decay of apoazurin derived from Pseudomonas aeruginosa is monoexponential. By this criterion the population of molecules of apoazurin is homogeneous. The emission anisotropy factor and the absorption anisotropy factor at the red edge of the absorption band assume similar values, showing that the tryptophan residue in apoazurin has the same asymmetric environment both in the ground and excited states. This finding suggests tight packing of the protein at the tryptophan environment. Native azurin does not decay monoexponentially. Moreover, comparison between the quantum yield calculated from the decay kinetics and the one measured directly shows that the majority of the azurin molecules are not fluorescent. There is thus variability in the structure of azurin molecules with an equilibration time that is longer than the fluorescence lifetime. Different asymmetric environment was found for the tryptophan residue in oxidized and reduced holoprotein and in apoazurin, as studied by the circular polarization of the fluorescence. D(2)O increases the fluorescence lifetime of apoazurin by 6 percent, compared to the lifetime in H(2)O solution; therefore water molecules may have access to the tryptophan residue, though the latter is situated in a hydrophobic environment.", "contents": "Homogeneity and variability in the structure of azurin molecules studied by fluorescence decay and circular polarization. The fluorescence decay of apoazurin derived from Pseudomonas aeruginosa is monoexponential. By this criterion the population of molecules of apoazurin is homogeneous. The emission anisotropy factor and the absorption anisotropy factor at the red edge of the absorption band assume similar values, showing that the tryptophan residue in apoazurin has the same asymmetric environment both in the ground and excited states. This finding suggests tight packing of the protein at the tryptophan environment. Native azurin does not decay monoexponentially. Moreover, comparison between the quantum yield calculated from the decay kinetics and the one measured directly shows that the majority of the azurin molecules are not fluorescent. There is thus variability in the structure of azurin molecules with an equilibration time that is longer than the fluorescence lifetime. Different asymmetric environment was found for the tryptophan residue in oxidized and reduced holoprotein and in apoazurin, as studied by the circular polarization of the fluorescence. D(2)O increases the fluorescence lifetime of apoazurin by 6 percent, compared to the lifetime in H(2)O solution; therefore water molecules may have access to the tryptophan residue, though the latter is situated in a hydrophobic environment."}
{"id": "PMID:235971", "title": "Binding kinetics of mercury(II) TO POLYRIBONUCLEOTIDES.", "content": "Kinetic studies of the interaction of Hg(II) with polyribonucleotides have been used to investigate structural fluctuations of the bases in nucleic acids. The reaction of Hg(II) with poly(A)-poly(U) occurs in two phases which differ in time scale by a factor of about 100. The slow phase is first order and exhibits cooperativity or autocatalytic kinetics. The rate is found to increase as decreasing chain length of poly(U) is used to make the double helical complex. The reaction appears to initiate at the ends of poly(U) strands and may be associated with a molecular rearrangement which results in strand separation with Hg(II) being linked only to uridine. The fast reaction phase is second order ans shows little cooperative behavior. Protons are released at this stage indicating alteration of the double helix. The measured second-order rate constant is nearly three orders of magnitude smaller than that found for poly(U) alone. This rate difference suggests that the reactive sites are blocked by double helix formation, and become available for reaction with Hg(II) only through a structural fluctuation. The ratio of rate constants for the reaction of Hg(II) with poly(U) and poly(A)-poly(U) was used to place an upper limit on the equilibrium constant for the structural fluctuation of 2 times 10- minus 3 at 15 degrees and 0.5 M NaClO4. The heat of the \"breathing\" reaction can be estimated to be similar to 9 kcal/mol from comparison of the temperature coefficient of the reaction with poly(U) to that with poly(A)-poly(U).", "contents": "Binding kinetics of mercury(II) TO POLYRIBONUCLEOTIDES. Kinetic studies of the interaction of Hg(II) with polyribonucleotides have been used to investigate structural fluctuations of the bases in nucleic acids. The reaction of Hg(II) with poly(A)-poly(U) occurs in two phases which differ in time scale by a factor of about 100. The slow phase is first order and exhibits cooperativity or autocatalytic kinetics. The rate is found to increase as decreasing chain length of poly(U) is used to make the double helical complex. The reaction appears to initiate at the ends of poly(U) strands and may be associated with a molecular rearrangement which results in strand separation with Hg(II) being linked only to uridine. The fast reaction phase is second order ans shows little cooperative behavior. Protons are released at this stage indicating alteration of the double helix. The measured second-order rate constant is nearly three orders of magnitude smaller than that found for poly(U) alone. This rate difference suggests that the reactive sites are blocked by double helix formation, and become available for reaction with Hg(II) only through a structural fluctuation. The ratio of rate constants for the reaction of Hg(II) with poly(U) and poly(A)-poly(U) was used to place an upper limit on the equilibrium constant for the structural fluctuation of 2 times 10- minus 3 at 15 degrees and 0.5 M NaClO4. The heat of the \"breathing\" reaction can be estimated to be similar to 9 kcal/mol from comparison of the temperature coefficient of the reaction with poly(U) to that with poly(A)-poly(U)."}
{"id": "PMID:235972", "title": "Endoribonuclease from bovine adrenal cortex cytosol.", "content": "An endoribonuclease which digests a variety of synthetic homoribopolymers and poly(A)-rich mRNA has been identified and purified greater than 500-fold with respect to specific activity from bovine adrenal cortex cytosol. Enzymatic digestion of synthetic poly(riboadenylic acid) was stimulated by Mn-2+ and Mg-2+ and the enzyme exhibited broad pH and salt optima. Poly(cytidylic acid) and poly(uridylic acid), but not poly(guanylic acid), served as substrates for the enzyme preparation; double-stranded RNA, DNA, and DNA-RNA hybrids were not digested by the enzyme. Digestion generated oligonucleotides with 3-hydroxyl and 5'-monophosphoester termini. On isoelectric focusing, the enzymatic activity banded at pH 8.3 plus or minus 0.2. An initial preferential cleavage of the poly(A) tract of poly(A)-rich RNA is suggested by the rapid appearance of a 4-6S digestion product highly enriched for adenylic acid; however, progressive digestion of the RNA occurs with additional incubation.", "contents": "Endoribonuclease from bovine adrenal cortex cytosol. An endoribonuclease which digests a variety of synthetic homoribopolymers and poly(A)-rich mRNA has been identified and purified greater than 500-fold with respect to specific activity from bovine adrenal cortex cytosol. Enzymatic digestion of synthetic poly(riboadenylic acid) was stimulated by Mn-2+ and Mg-2+ and the enzyme exhibited broad pH and salt optima. Poly(cytidylic acid) and poly(uridylic acid), but not poly(guanylic acid), served as substrates for the enzyme preparation; double-stranded RNA, DNA, and DNA-RNA hybrids were not digested by the enzyme. Digestion generated oligonucleotides with 3-hydroxyl and 5'-monophosphoester termini. On isoelectric focusing, the enzymatic activity banded at pH 8.3 plus or minus 0.2. An initial preferential cleavage of the poly(A) tract of poly(A)-rich RNA is suggested by the rapid appearance of a 4-6S digestion product highly enriched for adenylic acid; however, progressive digestion of the RNA occurs with additional incubation."}
{"id": "PMID:235973", "title": "Photoexcited bacterial bioluminescence. Identity and properties of the photoexcitable luciferase.", "content": "Properties of photoexcitable luciferase are compared with those of luciferase, both isolated from the bacterium Beneckea harveyi. The proteins have the same molecular weight, are similarly charged at pH 8, and can be inactivated, with comparable efficiencies, by antibodies against either pure luciferase (a heterodimeric protein) or individual subunits thereof. Compared with luciferase, photoexcitable luciferase has a broader pH range for optimal activity, is more stable under acidic conditions, is less stable under alkaline conditions, and is more resistant at neutral pH to inactivation by heat, urea, and trypsin; A flavine-like chromophore, designated B, can be isolated from photoexcitable luciferase. The binding of B to luciferase restores all the properties characteristic of photoexcitable luciferase. Moreover, photoexcitable luciferases from mutants selected to have heat labile luciferases are also thermally unstable. It is concluded that photoexcitable luciferase actually consists of a luciferase-B complex which is conformationally distinct from luciferase under certain conditions.", "contents": "Photoexcited bacterial bioluminescence. Identity and properties of the photoexcitable luciferase. Properties of photoexcitable luciferase are compared with those of luciferase, both isolated from the bacterium Beneckea harveyi. The proteins have the same molecular weight, are similarly charged at pH 8, and can be inactivated, with comparable efficiencies, by antibodies against either pure luciferase (a heterodimeric protein) or individual subunits thereof. Compared with luciferase, photoexcitable luciferase has a broader pH range for optimal activity, is more stable under acidic conditions, is less stable under alkaline conditions, and is more resistant at neutral pH to inactivation by heat, urea, and trypsin; A flavine-like chromophore, designated B, can be isolated from photoexcitable luciferase. The binding of B to luciferase restores all the properties characteristic of photoexcitable luciferase. Moreover, photoexcitable luciferases from mutants selected to have heat labile luciferases are also thermally unstable. It is concluded that photoexcitable luciferase actually consists of a luciferase-B complex which is conformationally distinct from luciferase under certain conditions."}
{"id": "PMID:235974", "title": "Regulation of Escherichia coli glutamine synthetase. Evidence for the action of some feedback modifiers at the active site of the unadenylylated enzyme.", "content": "The interaction of unadenylylated form of Escherichia coli glutamine synthetase with several substrates and effectors has been examined by magnetic resonance techniques. These studies show that two manganese ions bind per enzyme subunit. From the dramatic line broadening observed in the alanine spectra in the presence of manganese and enzyme, it is concluded that the binding of alanine occurs at a site nearer one of the two manganese sites. Electron spin resonance (ESR) titration experiments suggest apparent dissociation constants of 20 and 120 muM for manganese to these sites in the presence of 1.0 mM magnesium ion. The manganese concentration dependence of the broadening of alanine suggests an affinity of 30 muM for the manganese closest to the alanine binding site. This suggests that alanine binds closer to the more tightly bound manganese ion. Glutamate appears to displace the alanine and also appears to bind close to the strongly bound manganese ion. It is proposed that alanine and glutamine bind competitively and in the same site. The binding of alanine and ATP is shown to thermodynamically interact such that the presence of one ligand increases the affinity of the enzyme for the other ligand. The presence of ATP dramatically sharpens the alanine line width when manganese and glutamine synthetase are present. Addition of ADP or phosphate alone has little effect on the alanine line width but the addition of both ADP and phosphate shows the same dramatic sharpening as the addition of ATP alone, suggesting an induced fit conformational change in the enzyme induced by ATP or by both ADP and phosphate. A binding scheme is proposed in which all feedback inhibitors of the enzyme bind in a competitive fashion with substrates.", "contents": "Regulation of Escherichia coli glutamine synthetase. Evidence for the action of some feedback modifiers at the active site of the unadenylylated enzyme. The interaction of unadenylylated form of Escherichia coli glutamine synthetase with several substrates and effectors has been examined by magnetic resonance techniques. These studies show that two manganese ions bind per enzyme subunit. From the dramatic line broadening observed in the alanine spectra in the presence of manganese and enzyme, it is concluded that the binding of alanine occurs at a site nearer one of the two manganese sites. Electron spin resonance (ESR) titration experiments suggest apparent dissociation constants of 20 and 120 muM for manganese to these sites in the presence of 1.0 mM magnesium ion. The manganese concentration dependence of the broadening of alanine suggests an affinity of 30 muM for the manganese closest to the alanine binding site. This suggests that alanine binds closer to the more tightly bound manganese ion. Glutamate appears to displace the alanine and also appears to bind close to the strongly bound manganese ion. It is proposed that alanine and glutamine bind competitively and in the same site. The binding of alanine and ATP is shown to thermodynamically interact such that the presence of one ligand increases the affinity of the enzyme for the other ligand. The presence of ATP dramatically sharpens the alanine line width when manganese and glutamine synthetase are present. Addition of ADP or phosphate alone has little effect on the alanine line width but the addition of both ADP and phosphate shows the same dramatic sharpening as the addition of ATP alone, suggesting an induced fit conformational change in the enzyme induced by ATP or by both ADP and phosphate. A binding scheme is proposed in which all feedback inhibitors of the enzyme bind in a competitive fashion with substrates."}
{"id": "PMID:235975", "title": "Purification and properties of a yeast protein kinase.", "content": "A protein phosphokinase (EC 2.7.1.1.37) was isolated from baker's yeast (Saccharomyces cerevisiae) after a 17,000-fold purification; the purified enzyme is homogeneous according to the criteria of gel electrophoresis and ultracentrifuge analysis. The enzyme has a high isoelectric point of ca. 9 and appears to exist as a monomer with a molecular weight of 42,000 plus or minus 1500. It is neither stimulated by cyclic 3',5'-AMP, -GMP, -CMP or -ump nor inhibited by the regulatory subunit of rabbit muscle protein kinase (Reimann, E. M., Walsh, D. A., and Krebs, E. G. (1971), J. Biol. Chem. 246, 1986). In the presence of divalent metal ions, preferably Mg-2+ or Mn-2+, the enzyme readily transfers the terminal phosphate group of ATP to phosvitin, alphaS1B- and beta a-casein and an NH2-terminal tryptic peptide derived from beta a-casein, but not to protamine, lysine, or arginine-rich histones or to yeast enzymes such as phosphorylase, phosphofructokinase, or pyruvate carboxylase; serine and polyserine were also inactive as phosphate acceptors. Km values of 0.17 mM for beta a-casein and 0.2 mMfor ATP were determined at 10 mM Mg-2+. The urified yeast protein kinase also catalyzes the reverse reaction, namely, the transfer of phosphate from fully phosphorylated beta a-casein or its NH2-terminal peptide to ADP resulting in the formation of ATP. AMP, GDP, UDP, and CDP did not serve as phosphate acceptors in this reaction. As observed by Rabinowitz and Lipmann (Rabinowitz, M., and Lipmann, F. (1960), J. Biol. Chem. 235, 1043) both reactions have different pHoptima with values of 7.5 for the forward reaction (phosphorylation of the proteins) and ca 5.2 for the formation of ATP; both are differently affected by salts. Phosphorylation of beta a-casein with [gamma-32-P]ATP followed by digestion of the labeled protein with trypsin indicated that all the radioactivity was exclusively introduced in an NH2-terminal peptide possessing the unique sequence: Glu-Ser(P)-Leu-Ser(P)-Ser(P)-Ser(P)-Glu-Glu...(Ribadeau-Dumas, B., Brignon, G., Grosclaude, F., and Mercier, J.-C. (1971), eur J. Biochem. 20, 264). By subjecting beta a-casein and its NH2-terminal peptide to the combined action of almond acid phosphatease and purified yeast protein kinase, it was determined that the phosphorylation and dephosphorylation reactions proceed randomly, i.e., all seryl phosphate residues are equally susceptible and that the rate of phosphorylation decreases drastically as the number of bound phosphate groups in the substrate diminishes.", "contents": "Purification and properties of a yeast protein kinase. A protein phosphokinase (EC 2.7.1.1.37) was isolated from baker's yeast (Saccharomyces cerevisiae) after a 17,000-fold purification; the purified enzyme is homogeneous according to the criteria of gel electrophoresis and ultracentrifuge analysis. The enzyme has a high isoelectric point of ca. 9 and appears to exist as a monomer with a molecular weight of 42,000 plus or minus 1500. It is neither stimulated by cyclic 3',5'-AMP, -GMP, -CMP or -ump nor inhibited by the regulatory subunit of rabbit muscle protein kinase (Reimann, E. M., Walsh, D. A., and Krebs, E. G. (1971), J. Biol. Chem. 246, 1986). In the presence of divalent metal ions, preferably Mg-2+ or Mn-2+, the enzyme readily transfers the terminal phosphate group of ATP to phosvitin, alphaS1B- and beta a-casein and an NH2-terminal tryptic peptide derived from beta a-casein, but not to protamine, lysine, or arginine-rich histones or to yeast enzymes such as phosphorylase, phosphofructokinase, or pyruvate carboxylase; serine and polyserine were also inactive as phosphate acceptors. Km values of 0.17 mM for beta a-casein and 0.2 mMfor ATP were determined at 10 mM Mg-2+. The urified yeast protein kinase also catalyzes the reverse reaction, namely, the transfer of phosphate from fully phosphorylated beta a-casein or its NH2-terminal peptide to ADP resulting in the formation of ATP. AMP, GDP, UDP, and CDP did not serve as phosphate acceptors in this reaction. As observed by Rabinowitz and Lipmann (Rabinowitz, M., and Lipmann, F. (1960), J. Biol. Chem. 235, 1043) both reactions have different pHoptima with values of 7.5 for the forward reaction (phosphorylation of the proteins) and ca 5.2 for the formation of ATP; both are differently affected by salts. Phosphorylation of beta a-casein with [gamma-32-P]ATP followed by digestion of the labeled protein with trypsin indicated that all the radioactivity was exclusively introduced in an NH2-terminal peptide possessing the unique sequence: Glu-Ser(P)-Leu-Ser(P)-Ser(P)-Ser(P)-Glu-Glu...(Ribadeau-Dumas, B., Brignon, G., Grosclaude, F., and Mercier, J.-C. (1971), eur J. Biochem. 20, 264). By subjecting beta a-casein and its NH2-terminal peptide to the combined action of almond acid phosphatease and purified yeast protein kinase, it was determined that the phosphorylation and dephosphorylation reactions proceed randomly, i.e., all seryl phosphate residues are equally susceptible and that the rate of phosphorylation decreases drastically as the number of bound phosphate groups in the substrate diminishes."}
{"id": "PMID:235976", "title": "Stable, nonreducible cross-links of mature collagen.", "content": "During in vivo maturation, and also during in vitro incubation with physiological buffers, native collagen fibers display a progressive increase in tensile strength and insolubility. Paralleling these physiologically important changes is a progressive loss of the reducible cross-links which initially join the triple-chained subunits of collagen fibers. Although there is evidence suggesting that the reducible cross-links are gradually transformed into more stable, nonreducible cross-links during maturation, the nature of the transformation process and the structure of the stable \"mature\" cross-links has remained a mystery. In order to test the possibility that cross-link transformation involves addition of a nucleophilic amino acid residue to the reducible cross-links, histidine, arginine, glutamate, aspartate, lysine, and hydroxylysine residues were chemically modified, and the effect of each modification procedure on the in vitro transformation of reducible cross-links was ascertained. The results of these experiments indicated that destruction of histidine, arginine, glutamate, and aspartate residues has no measurable effect on the rate and extent of reducible cross-link transformation in hard tissue collagens. In contrast, modification of lysine and hydrocylysine residues with a wide variety of specific reagents completely blocks the transformation of reducible cross-links. Removal of the reversible blocking groups from lysine and hydroxlylysine residues then allows the transformation to proceed normally. These results indicate that collagen maturation involves nucleophilic addition of lysine and/or hydroxylysine residues to the electrophilic double bond of the reducible cross-links, yielding derivatives which are not only more stable but also capable of cross-linking more collagen molecules than their reducible precursors.", "contents": "Stable, nonreducible cross-links of mature collagen. During in vivo maturation, and also during in vitro incubation with physiological buffers, native collagen fibers display a progressive increase in tensile strength and insolubility. Paralleling these physiologically important changes is a progressive loss of the reducible cross-links which initially join the triple-chained subunits of collagen fibers. Although there is evidence suggesting that the reducible cross-links are gradually transformed into more stable, nonreducible cross-links during maturation, the nature of the transformation process and the structure of the stable \"mature\" cross-links has remained a mystery. In order to test the possibility that cross-link transformation involves addition of a nucleophilic amino acid residue to the reducible cross-links, histidine, arginine, glutamate, aspartate, lysine, and hydroxylysine residues were chemically modified, and the effect of each modification procedure on the in vitro transformation of reducible cross-links was ascertained. The results of these experiments indicated that destruction of histidine, arginine, glutamate, and aspartate residues has no measurable effect on the rate and extent of reducible cross-link transformation in hard tissue collagens. In contrast, modification of lysine and hydrocylysine residues with a wide variety of specific reagents completely blocks the transformation of reducible cross-links. Removal of the reversible blocking groups from lysine and hydroxlylysine residues then allows the transformation to proceed normally. These results indicate that collagen maturation involves nucleophilic addition of lysine and/or hydroxylysine residues to the electrophilic double bond of the reducible cross-links, yielding derivatives which are not only more stable but also capable of cross-linking more collagen molecules than their reducible precursors."}
{"id": "PMID:235977", "title": "NMR studies on phospholipid bilayers. Some factors affecting lipid distribution.", "content": "1. 1H-NMR and 31P-NMR are used to measure the outside/inside distribution of phospholipids in mixed vesicles. 2. Ferricyanide is a suitable shift reagent for measuring the outside/inside ratio of lecithin using 1H-NMR even when the phospholipid mixture contains negative lipids. 3. 31P-NMR can be used to measure the distribution of all phospholipids present provided the resonances are separated. 4. At 36.4 MHz the inside and outside phosphorus in lecithin vesicles have different chemical shifts. The separation at room temperature is 4-5 Hz and the individual linewidths are about 4Hz. 5. In a mixture of lecithin with phosphatidylethanolamine the latter has preference for the inside layer of the bilayer. The same holds for mixtures of lecithin with phosphatidylserine, phosphatidylinositol and phosphatidic acid. 6. In mixtures of lecithin and phosphatidylserine the preference of the latter for the inside is increased at lower pH under which conditions the negative charge of the phosphatidylserine is decreased. 7. In mixtures of lecithin with sphingomyelin the lecithin has a higher concentration at the inside. 8. The effect of vesicle size on the 31P-NMR linewidth and the temperature dependence of this linewidth is in agreement with the conclusion of Berden et al. (FEBS Lett. (1974), 46, 55-58) that the chemical shift anisotropy, modulated by the isotropic tumbling of the vesicles, makes a contribution to the linewidth. The chemical shift difference between outside and inside phosphorus can be used as a parameter for the measurement of the packing density at the inside and of the size of the vesicles. 9. It is concluded that both charge and the packing properties of the head group are major factors in determining the distribution of phospholipids in mixed vesicles.", "contents": "NMR studies on phospholipid bilayers. Some factors affecting lipid distribution. 1. 1H-NMR and 31P-NMR are used to measure the outside/inside distribution of phospholipids in mixed vesicles. 2. Ferricyanide is a suitable shift reagent for measuring the outside/inside ratio of lecithin using 1H-NMR even when the phospholipid mixture contains negative lipids. 3. 31P-NMR can be used to measure the distribution of all phospholipids present provided the resonances are separated. 4. At 36.4 MHz the inside and outside phosphorus in lecithin vesicles have different chemical shifts. The separation at room temperature is 4-5 Hz and the individual linewidths are about 4Hz. 5. In a mixture of lecithin with phosphatidylethanolamine the latter has preference for the inside layer of the bilayer. The same holds for mixtures of lecithin with phosphatidylserine, phosphatidylinositol and phosphatidic acid. 6. In mixtures of lecithin and phosphatidylserine the preference of the latter for the inside is increased at lower pH under which conditions the negative charge of the phosphatidylserine is decreased. 7. In mixtures of lecithin with sphingomyelin the lecithin has a higher concentration at the inside. 8. The effect of vesicle size on the 31P-NMR linewidth and the temperature dependence of this linewidth is in agreement with the conclusion of Berden et al. (FEBS Lett. (1974), 46, 55-58) that the chemical shift anisotropy, modulated by the isotropic tumbling of the vesicles, makes a contribution to the linewidth. The chemical shift difference between outside and inside phosphorus can be used as a parameter for the measurement of the packing density at the inside and of the size of the vesicles. 9. It is concluded that both charge and the packing properties of the head group are major factors in determining the distribution of phospholipids in mixed vesicles."}
{"id": "PMID:235978", "title": "A thermally induced alteration in lysosome membranes: salt permeability at 0 and 37 degrees C.", "content": "Preparations of radioactive lysosomes were obtained from mouse kidney after injection of radioactive iodine-labeled bovine ribonuclease. Stability of these lysosomes in various media was estimated from measurements of proteolytic activity towards the ribonuclease, and of ribonuclease retention in particles. The lysosomes were stable at 37 degrees C in isotonic, sucrose-free solutions of KCl, NaCl, and potassium acetate, and in mixtures of these with MgCl2, showing that these salts are relatively impermeant through the lysosomal membranes. The membranes were less permeable to Na+ than to K+. Both KCl and NaCl exerted their optimal protective effects over a broad concentration range above 0.125 M in 0.025 M acetate buffer. Mg2+ enhanced the protective effect of both K4 and Na+; the osmotic effect of 0.075 M NaC1-0.05 M MgCl2 was indistinguishable during the entire course of ribonuclease digestion from that of isotonic sucrose. Osmotic protection by KC1-MgC12 was demonstrated over the H range5.5-7.0. A marked alteration in membrane properties occurs at lower temperatures in 0.11 M KC1-0.01 M MgCl2 such that, at 0 degrees C, K+ permeability is much higher than at 37 degrees C, as shown by a several-fold decrease in stability at the lower temperature.", "contents": "A thermally induced alteration in lysosome membranes: salt permeability at 0 and 37 degrees C. Preparations of radioactive lysosomes were obtained from mouse kidney after injection of radioactive iodine-labeled bovine ribonuclease. Stability of these lysosomes in various media was estimated from measurements of proteolytic activity towards the ribonuclease, and of ribonuclease retention in particles. The lysosomes were stable at 37 degrees C in isotonic, sucrose-free solutions of KCl, NaCl, and potassium acetate, and in mixtures of these with MgCl2, showing that these salts are relatively impermeant through the lysosomal membranes. The membranes were less permeable to Na+ than to K+. Both KCl and NaCl exerted their optimal protective effects over a broad concentration range above 0.125 M in 0.025 M acetate buffer. Mg2+ enhanced the protective effect of both K4 and Na+; the osmotic effect of 0.075 M NaC1-0.05 M MgCl2 was indistinguishable during the entire course of ribonuclease digestion from that of isotonic sucrose. Osmotic protection by KC1-MgC12 was demonstrated over the H range5.5-7.0. A marked alteration in membrane properties occurs at lower temperatures in 0.11 M KC1-0.01 M MgCl2 such that, at 0 degrees C, K+ permeability is much higher than at 37 degrees C, as shown by a several-fold decrease in stability at the lower temperature."}
{"id": "PMID:235979", "title": "The effect of 1-ethyl-3(3-dimethylaminopropyl)carbodiimide on calcium binding and associated changes in chloroplast structure and chlorophyll a fluorescence in spinach chloroplasts.", "content": "1. Chemical modification of carboxyl groups on the chloroplast membrane with a water-soluble carbodiimide plus a nucleophile caused inhibition of Ca-2plus binding. 2. Both binding sites were affected and showed a decrease in the number of binding sites and an increase in the dissociation constant. 3. Cation-induced changes in chlorophyll a fluorescence and structural changes (deltaA540) were inhibited at the same carbodiimide concentrations as Ca-2plus binding, emphasizing the relationship between these processes. 4. Chloroplasts that were illuminated with high intensity light for short time periods showed a decrease in the carbodiimide-mediated inhibition of Ca-2plus binding.", "contents": "The effect of 1-ethyl-3(3-dimethylaminopropyl)carbodiimide on calcium binding and associated changes in chloroplast structure and chlorophyll a fluorescence in spinach chloroplasts. 1. Chemical modification of carboxyl groups on the chloroplast membrane with a water-soluble carbodiimide plus a nucleophile caused inhibition of Ca-2plus binding. 2. Both binding sites were affected and showed a decrease in the number of binding sites and an increase in the dissociation constant. 3. Cation-induced changes in chlorophyll a fluorescence and structural changes (deltaA540) were inhibited at the same carbodiimide concentrations as Ca-2plus binding, emphasizing the relationship between these processes. 4. Chloroplasts that were illuminated with high intensity light for short time periods showed a decrease in the carbodiimide-mediated inhibition of Ca-2plus binding."}
{"id": "PMID:235980", "title": "Delayed light studies on photosynthetic energy conversion. VIII. Evidence from millisecond emission of chloroplasts for two adenylate binding sites on membrane-bound coupling factor, CF1.", "content": "Effects of adenylates on chloroplast delayed light emission, at millisecond dark times, are inverse to the previously characterized effects of adenylates on electron transport rates. Either ADP alone or ATP alone increase intensity of delayed light, while ADP plus Pi decrease it. ADP alone requires the presence of an electron acceptor to have this effect on delayed light, but ATP does not. All three adenylate effects are abolished by uncoupling with gramicidin, by partial removal of photophosphorylation coupling factor (CF1) with EDTA, and by antibody to CF1. Readdition of CF1 re-established the adenylate effects in EDTA-stripped membranes. The three adenylate effects are differentially sensitive to pH, and pH differentially affected their abolition by antibody to CF1. The two adenylate effects shown in the absence of Pi are exhibited at lower adenylate concentrations than the ADP plus Pi effect, and are also less sensitive to phloridzin. These results are discussed in terms of probable adenylate effects on membrane-bound chloroplast coupling factor, CF1. At least two ADP binding sites would differ with respect to adenylate concentration for half maximal binding; pH of optimal binding capacity; phloridzin sensitivity; and functional regulation of electron transport, proton uptake, and energy storage within the membrane as measured by delayed light emission. It remains unclear whether the high affinity ADP binding site is identical to a high affinity ATP binding site on CF1.", "contents": "Delayed light studies on photosynthetic energy conversion. VIII. Evidence from millisecond emission of chloroplasts for two adenylate binding sites on membrane-bound coupling factor, CF1. Effects of adenylates on chloroplast delayed light emission, at millisecond dark times, are inverse to the previously characterized effects of adenylates on electron transport rates. Either ADP alone or ATP alone increase intensity of delayed light, while ADP plus Pi decrease it. ADP alone requires the presence of an electron acceptor to have this effect on delayed light, but ATP does not. All three adenylate effects are abolished by uncoupling with gramicidin, by partial removal of photophosphorylation coupling factor (CF1) with EDTA, and by antibody to CF1. Readdition of CF1 re-established the adenylate effects in EDTA-stripped membranes. The three adenylate effects are differentially sensitive to pH, and pH differentially affected their abolition by antibody to CF1. The two adenylate effects shown in the absence of Pi are exhibited at lower adenylate concentrations than the ADP plus Pi effect, and are also less sensitive to phloridzin. These results are discussed in terms of probable adenylate effects on membrane-bound chloroplast coupling factor, CF1. At least two ADP binding sites would differ with respect to adenylate concentration for half maximal binding; pH of optimal binding capacity; phloridzin sensitivity; and functional regulation of electron transport, proton uptake, and energy storage within the membrane as measured by delayed light emission. It remains unclear whether the high affinity ADP binding site is identical to a high affinity ATP binding site on CF1."}
{"id": "PMID:235982", "title": "The respiratory chain in a ubiquinone-deficient mutant of Saccharomyces cerevisiae.", "content": "1. Two allelic mutants of Saccharomyces cerevisiae with a deficiency in the biosynthesis of ubiquinone have been isolated. The properties of one particular mutant strain were investigated. Submitochondrial particles of this strain contain maximally 3% of the amount of ubiquinone in wild-type particles; the amounts of other components of the respiratory chain are essentially normal. 2. The respiratory rates of mutant cells, mitochondria and submitochondrial particles are low with ubiquinone-dependent substrates, but are restored to normal levels by addition of Q-1; the restored respiration is antimycin sensitive. Intact cells and mitochondria show respiratory control both in the absence and presence of Q-1. 3. The NADH:Q-1 oxidoreductase of submitochondrial particles of the mutant followspseudo first-order kinetics in [Q-1]. QH2-1 inhibits competitively with respect to Q-1, the Ki for QH2-1 being equal to the Km for Q-1. 4. Succinate dehydrogenase in both wild-type and mutant submitochondrial particles can be activated by NADH. 5. The turnover number of succinate dehydrogenase in the mutant, measured with phenazine methosulphate as primary electron acceptor, is about one-half that of wild-type particles. The turnover numbers measured with Q-1 as electron acceptor are about the same in the two types of particles. 6. The kinetics of redox changes in cytochrome b, in the presence of antimycin and oxygen, are distinctly different in the mutant and wild-type particles. They indicate that ubiquinone plays an important role in the phenomenon of the increased reducibility of cytochrome b induced by antimycin plus oxygen.", "contents": "The respiratory chain in a ubiquinone-deficient mutant of Saccharomyces cerevisiae. 1. Two allelic mutants of Saccharomyces cerevisiae with a deficiency in the biosynthesis of ubiquinone have been isolated. The properties of one particular mutant strain were investigated. Submitochondrial particles of this strain contain maximally 3% of the amount of ubiquinone in wild-type particles; the amounts of other components of the respiratory chain are essentially normal. 2. The respiratory rates of mutant cells, mitochondria and submitochondrial particles are low with ubiquinone-dependent substrates, but are restored to normal levels by addition of Q-1; the restored respiration is antimycin sensitive. Intact cells and mitochondria show respiratory control both in the absence and presence of Q-1. 3. The NADH:Q-1 oxidoreductase of submitochondrial particles of the mutant followspseudo first-order kinetics in [Q-1]. QH2-1 inhibits competitively with respect to Q-1, the Ki for QH2-1 being equal to the Km for Q-1. 4. Succinate dehydrogenase in both wild-type and mutant submitochondrial particles can be activated by NADH. 5. The turnover number of succinate dehydrogenase in the mutant, measured with phenazine methosulphate as primary electron acceptor, is about one-half that of wild-type particles. The turnover numbers measured with Q-1 as electron acceptor are about the same in the two types of particles. 6. The kinetics of redox changes in cytochrome b, in the presence of antimycin and oxygen, are distinctly different in the mutant and wild-type particles. They indicate that ubiquinone plays an important role in the phenomenon of the increased reducibility of cytochrome b induced by antimycin plus oxygen."}
{"id": "PMID:235983", "title": "Respiration-department uncoupler-stimulated ATPase activity in castor bean endosperm mitochondria and submitochondrial particles.", "content": "1. The uncoupler-stimulated ATPase activity of castor bean endosperm mitochondria and submitchondrial particles has been studied. The rate of ATP hydrolysis catalyzed by intact mitochondria was slow and little enhanced by addition of uncouplers at the concentration required for uncoupling the oxidative phosphorylation. ATP-ase activity was stimulated at higher concentrations of uncouplers. 2. 1-Anilinonaphthalene 8-sulfonate fluorescence was decreased when the mitochondria were oxidizing succinate. Carbonylcyanide-p-trifluoromethoxyphenylhydrazone and antimycin reversed the succinate-induced fluorescence diminution. ATP did not induce the fluorescence response. 3. The addition of succinate, NADH or ascorbate/N,N,N'-N'-tetramethyl-p-phenylenediamine as electron donor induced high ATPase activity in the presence of low concentrations of uncouplers. Stimulating effect of uncouplers was completely abolished by further addition of antimycin. 4. Submitochondrial particles were prepared by sonication. The particles catalyzed a rapid hydrolysis of ATP and carbonylcyanide-p-trifluoromethoxyphenylhydrazone at 10-8 M did not stimulate the ATPase activity. Addition of succinate induced uncoupler-stimulated ATPase activity. The effect of succinate was completely abolished by further addition of antimycin. 5. The treatment of submitochondrial particles by trypsin or high pH also induced uncoupler-stimulated ATPase activity. 6. The above results were interpreted to indicate that ATPase inhibitor regulated the back-flow reaction of mitochondrial oxidative phosphorylation.", "contents": "Respiration-department uncoupler-stimulated ATPase activity in castor bean endosperm mitochondria and submitochondrial particles. 1. The uncoupler-stimulated ATPase activity of castor bean endosperm mitochondria and submitchondrial particles has been studied. The rate of ATP hydrolysis catalyzed by intact mitochondria was slow and little enhanced by addition of uncouplers at the concentration required for uncoupling the oxidative phosphorylation. ATP-ase activity was stimulated at higher concentrations of uncouplers. 2. 1-Anilinonaphthalene 8-sulfonate fluorescence was decreased when the mitochondria were oxidizing succinate. Carbonylcyanide-p-trifluoromethoxyphenylhydrazone and antimycin reversed the succinate-induced fluorescence diminution. ATP did not induce the fluorescence response. 3. The addition of succinate, NADH or ascorbate/N,N,N'-N'-tetramethyl-p-phenylenediamine as electron donor induced high ATPase activity in the presence of low concentrations of uncouplers. Stimulating effect of uncouplers was completely abolished by further addition of antimycin. 4. Submitochondrial particles were prepared by sonication. The particles catalyzed a rapid hydrolysis of ATP and carbonylcyanide-p-trifluoromethoxyphenylhydrazone at 10-8 M did not stimulate the ATPase activity. Addition of succinate induced uncoupler-stimulated ATPase activity. The effect of succinate was completely abolished by further addition of antimycin. 5. The treatment of submitochondrial particles by trypsin or high pH also induced uncoupler-stimulated ATPase activity. 6. The above results were interpreted to indicate that ATPase inhibitor regulated the back-flow reaction of mitochondrial oxidative phosphorylation."}
{"id": "PMID:235984", "title": "Physicochemical properties of flavodoxin from Desulfovibrio vulgaris.", "content": "Reductive titration curves of flavodoxin from Desulfovibrio vulgaris displayed two one-electron steps. The redox potential E-2 for the couple oxidized flavodoxin/flavodoxin semiquinone was determined by direct titration with dithionite. E-2 was -149 plus or minus 3 mV (pH 7.78, 25 degrees C). The redox potential E-1 for the couple flavodoxin semiquinone/fully reduced flavodoxin was deduced from the equilibrium concentration of these species in the presence of hydrogenase and H-2. E-1 was -438 plus or minus 8 mV (pH 7.78, 25 degrees C). Light-absorption and fluorescence spectra of flavodoxin in its three redox states have been recorded. Both the rate and extent of reduction of flavodoxin semiguinone with dithionite were found to depend on pH. An equilibrium between the semiquinone and hydroquinone forms occurred at pH values close to the neutrality, even in the presence of a large excess of dithionite, suggesting an ionization in fully reduced flavodoxin with a pK-a = 6.6. The association constants K for the three FMN redox forms with the apoprotein were deduced from the value of K (K = 8 times 10-7 M-1) measured with oxidized EMN at pH 7.0. Oxidized flavodoxin was found to comproportionate with the fully reduced protein (k-comp = 4.3 times 10-3 M-1 times s-1, pH 9.0, 22 degrees C) and with reduced free FMN (K-comp = 44 M-1 times s-1, pH 8.1, 20 degrees C). Fast oxidation of reduced flavodoxin occurred in the presence of O-2. Slower oxidation of semiquinone was dependent on pH in a drastic way.", "contents": "Physicochemical properties of flavodoxin from Desulfovibrio vulgaris. Reductive titration curves of flavodoxin from Desulfovibrio vulgaris displayed two one-electron steps. The redox potential E-2 for the couple oxidized flavodoxin/flavodoxin semiquinone was determined by direct titration with dithionite. E-2 was -149 plus or minus 3 mV (pH 7.78, 25 degrees C). The redox potential E-1 for the couple flavodoxin semiquinone/fully reduced flavodoxin was deduced from the equilibrium concentration of these species in the presence of hydrogenase and H-2. E-1 was -438 plus or minus 8 mV (pH 7.78, 25 degrees C). Light-absorption and fluorescence spectra of flavodoxin in its three redox states have been recorded. Both the rate and extent of reduction of flavodoxin semiguinone with dithionite were found to depend on pH. An equilibrium between the semiquinone and hydroquinone forms occurred at pH values close to the neutrality, even in the presence of a large excess of dithionite, suggesting an ionization in fully reduced flavodoxin with a pK-a = 6.6. The association constants K for the three FMN redox forms with the apoprotein were deduced from the value of K (K = 8 times 10-7 M-1) measured with oxidized EMN at pH 7.0. Oxidized flavodoxin was found to comproportionate with the fully reduced protein (k-comp = 4.3 times 10-3 M-1 times s-1, pH 9.0, 22 degrees C) and with reduced free FMN (K-comp = 44 M-1 times s-1, pH 8.1, 20 degrees C). Fast oxidation of reduced flavodoxin occurred in the presence of O-2. Slower oxidation of semiquinone was dependent on pH in a drastic way."}
{"id": "PMID:235985", "title": "Chloroplast cytochrome b-6. Molecular composition as a lipoprotein.", "content": "Disc electrophoretically homogeneous spinach-chloroplast cytochrome b-6 was found to be a lipoprotein whose redox potential was essentially unchanged during isolation. These results further support the hypothesis of Triton X-100/4 M urea, pH 8, as a useful extracting medium for membrane lipoproteins. Cytochrome b-6 was found to have a heme equivalent dry weight of 1 mol of heme per 60000 g. Of this, 20000 g was lipid-extractable. The molecular weight was 60000 with a partial specific volume of 0.84 ml/g. The protein portion of the molecule (40000) consisted of 1 polypeptide chain of 20000 daltons, 1 of 9600 daltons and 2 of 6600 daltons. A simple lipid composition (relative to the original membrane) was found consisting of 7 mol of chlorophyll a and 6 mol of cardiolipin per mol of cytochrome; these two lipids thus account for about 75-80% of the lipid content. An unidentified minor neutral lipid and minor polar lipid were also detected. At pH 7.0 in the presence of 0.5% Triton X-100, E'-o was -0.080 V, and in the absence of Triton X-100, E'-o was -0.120 V. At pH 8 in 0.5% Triton X-100, E'-o was -0.084 V, thus indicating that the redox potential is independent of pH in the region 7-8. The redox reaction proceeded via a one-electron-transfer.", "contents": "Chloroplast cytochrome b-6. Molecular composition as a lipoprotein. Disc electrophoretically homogeneous spinach-chloroplast cytochrome b-6 was found to be a lipoprotein whose redox potential was essentially unchanged during isolation. These results further support the hypothesis of Triton X-100/4 M urea, pH 8, as a useful extracting medium for membrane lipoproteins. Cytochrome b-6 was found to have a heme equivalent dry weight of 1 mol of heme per 60000 g. Of this, 20000 g was lipid-extractable. The molecular weight was 60000 with a partial specific volume of 0.84 ml/g. The protein portion of the molecule (40000) consisted of 1 polypeptide chain of 20000 daltons, 1 of 9600 daltons and 2 of 6600 daltons. A simple lipid composition (relative to the original membrane) was found consisting of 7 mol of chlorophyll a and 6 mol of cardiolipin per mol of cytochrome; these two lipids thus account for about 75-80% of the lipid content. An unidentified minor neutral lipid and minor polar lipid were also detected. At pH 7.0 in the presence of 0.5% Triton X-100, E'-o was -0.080 V, and in the absence of Triton X-100, E'-o was -0.120 V. At pH 8 in 0.5% Triton X-100, E'-o was -0.084 V, thus indicating that the redox potential is independent of pH in the region 7-8. The redox reaction proceeded via a one-electron-transfer."}
{"id": "PMID:235986", "title": "The effect of o-phenanthroline on the midpoint potential of the primary electron acceptor of photosystem II.", "content": "The primary electron acceptor of Photosystem II has a midpoint oxidation-reduction potential of +95 mV at pH 7.0 in Photosystem II chloroplast fragments prepared by digitonin treatment. The midpoint potential of the acceptor has a pH dependence of -60 mV/pH unit. At concentrations that inhibit oxygen evolution, o-phenanthroline shifts the midpoint potential of the primary acceptor by +70 mV. The shifted potential retains the same dependence on pH. The effect of o-phenanthroline suggests that it interacts directly with the primary electron acceptor of photosystem II in a manner similar to that reported previously for the primary electron acceptor in purple photosynthetic bacteria.", "contents": "The effect of o-phenanthroline on the midpoint potential of the primary electron acceptor of photosystem II. The primary electron acceptor of Photosystem II has a midpoint oxidation-reduction potential of +95 mV at pH 7.0 in Photosystem II chloroplast fragments prepared by digitonin treatment. The midpoint potential of the acceptor has a pH dependence of -60 mV/pH unit. At concentrations that inhibit oxygen evolution, o-phenanthroline shifts the midpoint potential of the primary acceptor by +70 mV. The shifted potential retains the same dependence on pH. The effect of o-phenanthroline suggests that it interacts directly with the primary electron acceptor of photosystem II in a manner similar to that reported previously for the primary electron acceptor in purple photosynthetic bacteria."}
{"id": "PMID:235987", "title": "Studies on acetylcholinesterase and cholinesterase covalently bound to polymaleinic anhydride.", "content": "Acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) and cholinesterase (acylcholine acylhydrolase, EC 3.1.1.8), respectively, were covalently attached to a cross-linked copolymerisate of maleinic anhydride and butanediol-divinylether. Based on the coupling procedure reported by Br\u00fcmmer et al. (Brummer, W., Hennrich, N., Klockow, M., Lang, H. and Orth, H.D. (1972) Eur. J. Biochem. 2k, 129--135), a simple method is described which requires only 24 h for completion and provides a sufficient yield. Although a polyanionic carrier was used the Km and k2 values as well as the substrate and pH optima of the bound acetylcholinesterase and bound cholinesterase did not differ considerably from the corresponding values of the free enzymes. Bound acetylcholinesterase and to some extent also bound cholinesterase did not lose any enzymatic activity after storage in saline at 4 degrees C for 140 days.", "contents": "Studies on acetylcholinesterase and cholinesterase covalently bound to polymaleinic anhydride. Acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) and cholinesterase (acylcholine acylhydrolase, EC 3.1.1.8), respectively, were covalently attached to a cross-linked copolymerisate of maleinic anhydride and butanediol-divinylether. Based on the coupling procedure reported by Br\u00fcmmer et al. (Brummer, W., Hennrich, N., Klockow, M., Lang, H. and Orth, H.D. (1972) Eur. J. Biochem. 2k, 129--135), a simple method is described which requires only 24 h for completion and provides a sufficient yield. Although a polyanionic carrier was used the Km and k2 values as well as the substrate and pH optima of the bound acetylcholinesterase and bound cholinesterase did not differ considerably from the corresponding values of the free enzymes. Bound acetylcholinesterase and to some extent also bound cholinesterase did not lose any enzymatic activity after storage in saline at 4 degrees C for 140 days."}
{"id": "PMID:235988", "title": "L-ascorbic acid 2-sulphate. A substrate for mammalian arylsulphatases.", "content": "Ascorbic acid 2-sulphate has a stability in acid comparable to that of phenyl sulphate and is rather more acid-labile than simple carbohydrate sulphates. At its optimum pH of 4.8 sulphatase A(aryl-sulphate sulphohydrolase EC 3.1.6.1.) hydrolyses ascorbic acid sulphate with a specific activity of 90 mumol/mg per min (150 mumol/mg per min with nitrocatechol sulphate at pH 5.6). At pH 4.8 the kinetics are non-Michaelis. At pH 5.6 Michaelis kinetics are obeyed and Km 12 21 mM ascorbic acid 2-sulphate. K2SO4 is a competitive inhibitor with a Ki of 0.2 and 0.6 mM at pH 4.8 and 5.6, respectively. Sulphatase A is converted into a substrate-modified form during its hydrolysis of ascorbic acid sulphate. Sulphatase B also hydrolyses ascorbic acid 2-sulphate. At pH 4.8 and in the presence of 0.15 M NaCl the specific activity is 0.92 mumol/mg per min (90 mumol/mg per min for nitrocatechol sulphate at pH 5.6). In the absence of NaCl the activity is greatly decreased. Km is 8 mM. K2SO4 is a competitive inhibitor with a Ki of 0.1 mM. Ascorbic acid is not hydrolysed at a detectable rate by the arylsulphatases of the mollusc Dicathais orbita or of Aerobacter aerogenes.?", "contents": "L-ascorbic acid 2-sulphate. A substrate for mammalian arylsulphatases. Ascorbic acid 2-sulphate has a stability in acid comparable to that of phenyl sulphate and is rather more acid-labile than simple carbohydrate sulphates. At its optimum pH of 4.8 sulphatase A(aryl-sulphate sulphohydrolase EC 3.1.6.1.) hydrolyses ascorbic acid sulphate with a specific activity of 90 mumol/mg per min (150 mumol/mg per min with nitrocatechol sulphate at pH 5.6). At pH 4.8 the kinetics are non-Michaelis. At pH 5.6 Michaelis kinetics are obeyed and Km 12 21 mM ascorbic acid 2-sulphate. K2SO4 is a competitive inhibitor with a Ki of 0.2 and 0.6 mM at pH 4.8 and 5.6, respectively. Sulphatase A is converted into a substrate-modified form during its hydrolysis of ascorbic acid sulphate. Sulphatase B also hydrolyses ascorbic acid 2-sulphate. At pH 4.8 and in the presence of 0.15 M NaCl the specific activity is 0.92 mumol/mg per min (90 mumol/mg per min for nitrocatechol sulphate at pH 5.6). In the absence of NaCl the activity is greatly decreased. Km is 8 mM. K2SO4 is a competitive inhibitor with a Ki of 0.1 mM. Ascorbic acid is not hydrolysed at a detectable rate by the arylsulphatases of the mollusc Dicathais orbita or of Aerobacter aerogenes.?"}
{"id": "PMID:235989", "title": "Ribosomal RNA turnover and the level of ribonuclease activity in the liver of the pregnant rat.", "content": "Studies were undertaken on the turnover of ribosomal RNA and on ribonuclease activity in the liver of the pregnant rat in an attempt to explain the accumulation of liver RNA which occurs during the latter half of pregnancy. Between the 15th and 20th day of gestation the rate constant of degradation, biological half-life and daily rate of synthesis of ribosomal RNA were calculated to be 0.0887, 7.81 days and 6.21 mg per liver per 100g body weight respectively. Corresponding values in non-pregnant rats were 0.123, 5.68 days and 3.47 mg per liver per 100g body weight. The increase in RNA was therefore associated with an increase in its rate of synthesis and a decrease in its rate of breakdown. From the 14th day of pregnancy there was a decrease in alkaline ribonuclease activity and a marked increase in the level of alkaline ribonuclease inhibitor. The activity of acid ribonuclease was found to increase and that of acid phosphatase to decrease during this period.", "contents": "Ribosomal RNA turnover and the level of ribonuclease activity in the liver of the pregnant rat. Studies were undertaken on the turnover of ribosomal RNA and on ribonuclease activity in the liver of the pregnant rat in an attempt to explain the accumulation of liver RNA which occurs during the latter half of pregnancy. Between the 15th and 20th day of gestation the rate constant of degradation, biological half-life and daily rate of synthesis of ribosomal RNA were calculated to be 0.0887, 7.81 days and 6.21 mg per liver per 100g body weight respectively. Corresponding values in non-pregnant rats were 0.123, 5.68 days and 3.47 mg per liver per 100g body weight. The increase in RNA was therefore associated with an increase in its rate of synthesis and a decrease in its rate of breakdown. From the 14th day of pregnancy there was a decrease in alkaline ribonuclease activity and a marked increase in the level of alkaline ribonuclease inhibitor. The activity of acid ribonuclease was found to increase and that of acid phosphatase to decrease during this period."}
{"id": "PMID:235990", "title": "A trypsin-resistant heme peptide from cardiac cytochrome c1.", "content": "A tryptic resistant heme peptide has been prepared and purified from cardiac cytochrome c1. This purified peptide is not further hydrolyzed by reactions of other proteolytic enzymes, such as pronase. The peptide contains 2 residues each of serine, cysteine and valine, and 1 residue each of alanine, methionine, tyrosine, histidine, arginine, proline, glutamic acid (glutamine) and aspartic acid. The intensity of the absorption spectrum of the peptide has been found to be dependent upon, but the positions of the absorption maxima do not vary with, concentration. The heme peptide does not show multiple splitting of absorption peaks at liquid N2 temperatures as does the intact cytochrome C1. However, cyanide rapidly reacts with the peptide and causes significant spectral changes. CD spectra of the peptide exhibit a typical profile of a non-structured heme peptide with positive CD bands in the Soret region and around 250 nm, and a broad negative extreme of 320-360 nm. The similarities and differences between the tryptic resistant heme peptides from cytochromes c1 and c have been compared.", "contents": "A trypsin-resistant heme peptide from cardiac cytochrome c1. A tryptic resistant heme peptide has been prepared and purified from cardiac cytochrome c1. This purified peptide is not further hydrolyzed by reactions of other proteolytic enzymes, such as pronase. The peptide contains 2 residues each of serine, cysteine and valine, and 1 residue each of alanine, methionine, tyrosine, histidine, arginine, proline, glutamic acid (glutamine) and aspartic acid. The intensity of the absorption spectrum of the peptide has been found to be dependent upon, but the positions of the absorption maxima do not vary with, concentration. The heme peptide does not show multiple splitting of absorption peaks at liquid N2 temperatures as does the intact cytochrome C1. However, cyanide rapidly reacts with the peptide and causes significant spectral changes. CD spectra of the peptide exhibit a typical profile of a non-structured heme peptide with positive CD bands in the Soret region and around 250 nm, and a broad negative extreme of 320-360 nm. The similarities and differences between the tryptic resistant heme peptides from cytochromes c1 and c have been compared."}
{"id": "PMID:235991", "title": "The excretion of hydrogen ion by the isolated amphibian skin: effects of antidiuretic hormone and amiloride.", "content": "H+ extrusion by the isolated skins of two amphibia, Rana ridibunda and Bufo bufo, was studied in order to test for the presence of exchange mechanisms of the type Na+/H+ and Cl-/HCO3-, which have been described in several epithelial structures. The preparations were mounted in chambers of the Ussing type, so that the short-circuit current could be used as a function of Na+ transport and the pH-stat techinique was utilize to determine the rates of H+ extrusion under different experimental conditions. The conditions were either the withdrawal of the ions intervening the mentioned exchanges (Cl- or Na+), or the addition of drugs with well-known effects on Na+ up-take and transport (antidiuretic hormone and amiloride). In the frog skin, H+ excretion was detected in solutions containing either Cl- or SO4-2-, with identical rates. Again, Na+ substitution by Mg-2+ had no effect on H+ excretion rates, neither did the suppression of Na+ influx by amiloride or its stimulation by antidiuretic hormone. These experiments were repeated with similar results in gland-free preparations of the epidermis of frog skin separated from the corion by the action of collagenase. Experiments in toad skin that H+ excretion could not be detected whan Cl- was present in the outer medium, but became apparent if an impermant anion, SO4-2-, was used. This observation is compatible with the existence of an exchange mechanism of the type Cl-/HCO3-. Secondly, in these preparations H+ extrusion increased after stimulation with antidiuretic hormone and  decreased when amiloride was used or when Na+ was substituted by Mg+, suggesting that a least a fraction of the total H+ efflux is linked to Na+ influx. In the isolated frog skin this mechanism does not seem to be operative.", "contents": "The excretion of hydrogen ion by the isolated amphibian skin: effects of antidiuretic hormone and amiloride. H+ extrusion by the isolated skins of two amphibia, Rana ridibunda and Bufo bufo, was studied in order to test for the presence of exchange mechanisms of the type Na+/H+ and Cl-/HCO3-, which have been described in several epithelial structures. The preparations were mounted in chambers of the Ussing type, so that the short-circuit current could be used as a function of Na+ transport and the pH-stat techinique was utilize to determine the rates of H+ extrusion under different experimental conditions. The conditions were either the withdrawal of the ions intervening the mentioned exchanges (Cl- or Na+), or the addition of drugs with well-known effects on Na+ up-take and transport (antidiuretic hormone and amiloride). In the frog skin, H+ excretion was detected in solutions containing either Cl- or SO4-2-, with identical rates. Again, Na+ substitution by Mg-2+ had no effect on H+ excretion rates, neither did the suppression of Na+ influx by amiloride or its stimulation by antidiuretic hormone. These experiments were repeated with similar results in gland-free preparations of the epidermis of frog skin separated from the corion by the action of collagenase. Experiments in toad skin that H+ excretion could not be detected whan Cl- was present in the outer medium, but became apparent if an impermant anion, SO4-2-, was used. This observation is compatible with the existence of an exchange mechanism of the type Cl-/HCO3-. Secondly, in these preparations H+ extrusion increased after stimulation with antidiuretic hormone and  decreased when amiloride was used or when Na+ was substituted by Mg+, suggesting that a least a fraction of the total H+ efflux is linked to Na+ influx. In the isolated frog skin this mechanism does not seem to be operative."}
{"id": "PMID:235992", "title": "Raman and resonance-Raman scattering by erythrocyte ghosts.", "content": "1. We present the laser-Raman spectra of human erythrocyte ghosts, isolated by standard conditions and compare these with the spectra of lecithin liposomes and fat-free serum albumin. 2. The hydrocarbon stretching modes of membrane lipids are temperature sensitive and may serve as a index of hydrocarbon chain motion. 3. The Amide I and Amide III bands of ghosts in H-2O and 2-H-2O, indicate a mixture of alpha-helical and unordered conformation, but do not allow a quantitative estimate of secondary structure. 4. Strong, scattering bands at 1530 and 1165 cm-1 are attributable to conjugated double bond systems, probably of membrane-associated carotenoids. Their high intensity is due to resonance enhancement.", "contents": "Raman and resonance-Raman scattering by erythrocyte ghosts. 1. We present the laser-Raman spectra of human erythrocyte ghosts, isolated by standard conditions and compare these with the spectra of lecithin liposomes and fat-free serum albumin. 2. The hydrocarbon stretching modes of membrane lipids are temperature sensitive and may serve as a index of hydrocarbon chain motion. 3. The Amide I and Amide III bands of ghosts in H-2O and 2-H-2O, indicate a mixture of alpha-helical and unordered conformation, but do not allow a quantitative estimate of secondary structure. 4. Strong, scattering bands at 1530 and 1165 cm-1 are attributable to conjugated double bond systems, probably of membrane-associated carotenoids. Their high intensity is due to resonance enhancement."}
{"id": "PMID:235993", "title": "Gastric acid secretion in the lizard. Ionic requirements and effects of inhibitors.", "content": "1. The effects of ion substitution and various inhibitors on the transmucosal potential, short circuit current, mucosal resistance and acid secretion of the lizard gastric mucosa, incubated in an Ussing chamber, have been determined. 2. Ion substitution experiments indicate that the serosal potential step consists of a combined C1- and K+ diffusion potential, and that the mucosal potential step is Na+ dependent and behaves primarily as a Na+ diffusion potential. 3. Experiments with ouabain indicate that the major (Na+, K+)-ATPase activity responsible for maintenance of cation gradients is located on the serosal side of the mucosal cells, and that this pump activity is non-electrogenic. 4. Experiments with amiloride indicate that a passive sodium influx on the mucosal side is essential for the maintenance of the transmucosal potential and short circuit current. 5. Acid secretion requires the presence of sodium and chloride on the serosal side and the maintenance of a high intracellular potassium level through the (Na+, K+)-ATPase system. 6. The effects of acetazolamide and thiocyanate are compatible with an involvement of carbonic anhydrase and anion-dependent ATPase in acid secretion. 7. Upon initiation of acid secretion the serosal membrane permeability for chloride increases and that for potassium decreases.", "contents": "Gastric acid secretion in the lizard. Ionic requirements and effects of inhibitors. 1. The effects of ion substitution and various inhibitors on the transmucosal potential, short circuit current, mucosal resistance and acid secretion of the lizard gastric mucosa, incubated in an Ussing chamber, have been determined. 2. Ion substitution experiments indicate that the serosal potential step consists of a combined C1- and K+ diffusion potential, and that the mucosal potential step is Na+ dependent and behaves primarily as a Na+ diffusion potential. 3. Experiments with ouabain indicate that the major (Na+, K+)-ATPase activity responsible for maintenance of cation gradients is located on the serosal side of the mucosal cells, and that this pump activity is non-electrogenic. 4. Experiments with amiloride indicate that a passive sodium influx on the mucosal side is essential for the maintenance of the transmucosal potential and short circuit current. 5. Acid secretion requires the presence of sodium and chloride on the serosal side and the maintenance of a high intracellular potassium level through the (Na+, K+)-ATPase system. 6. The effects of acetazolamide and thiocyanate are compatible with an involvement of carbonic anhydrase and anion-dependent ATPase in acid secretion. 7. Upon initiation of acid secretion the serosal membrane permeability for chloride increases and that for potassium decreases."}
{"id": "PMID:235994", "title": "A poly(U) polymerase in tobacco leaves.", "content": "A poly(U) polymerizing enzyme has been found in healthy and tobacco mosaic virus-infected tobacco leaves and has been partially purified by affinity chromatography on a gel prepared from agarose with chemically coupled RNA. The enzyme is stimulated by Mn-2+ and dependent on a polynucleotide, preferentially poly(A). The synthesis proceeds optimally at pH 7.6 and 25 degrees C. The enzyme is highly specific for UTP and is inhibited by other ribonucleoside triphosphates. The product was partly sensitive to pancreatic ribonuclease. The synthetic reaction is inhibited in the presence of pyrophosphate but insensitive to 10 mM orthophosphate and high levels of cordycepin, rifampicin and actinomycin D. A molecular weight of about 40,000 has been estimated by sucrose gradient analysis and partition cell ultracentrifugation.", "contents": "A poly(U) polymerase in tobacco leaves. A poly(U) polymerizing enzyme has been found in healthy and tobacco mosaic virus-infected tobacco leaves and has been partially purified by affinity chromatography on a gel prepared from agarose with chemically coupled RNA. The enzyme is stimulated by Mn-2+ and dependent on a polynucleotide, preferentially poly(A). The synthesis proceeds optimally at pH 7.6 and 25 degrees C. The enzyme is highly specific for UTP and is inhibited by other ribonucleoside triphosphates. The product was partly sensitive to pancreatic ribonuclease. The synthetic reaction is inhibited in the presence of pyrophosphate but insensitive to 10 mM orthophosphate and high levels of cordycepin, rifampicin and actinomycin D. A molecular weight of about 40,000 has been estimated by sucrose gradient analysis and partition cell ultracentrifugation."}
{"id": "PMID:235995", "title": "Cyclization of three satellite components of calf thymus DNA.", "content": "Cyclization of denatured and reannealed satellite components of calf thymus DNA was studied by electron microscopy. All three satellite DNA components studied (1.707g/cm-3, 1.714g/cm-3 and 1.721g/cm-3) form circular structures indicating that the sequences of the calf thymus satellite DNAs are arranged in a tandemly repetitious manner. Under appropriate annealing conditions the amount of circular structures is reproducible and practically no aggregates are formed. By comparison of cyclization experiments under defined conditions it is demonstrated that individual satellite components differ in the amount of circular structures formed during reassociation and in the distribution of linear and circular molecules. From the distribution of the contour lengths of circular molecules we conclude that the length of the repetitive sequence decreases with increasing buoyant density of the satellite components. The average lengths of the repetitive sequences calculated from electron microscopy measurements are in good agreement with those from renaturation kinetics.", "contents": "Cyclization of three satellite components of calf thymus DNA. Cyclization of denatured and reannealed satellite components of calf thymus DNA was studied by electron microscopy. All three satellite DNA components studied (1.707g/cm-3, 1.714g/cm-3 and 1.721g/cm-3) form circular structures indicating that the sequences of the calf thymus satellite DNAs are arranged in a tandemly repetitious manner. Under appropriate annealing conditions the amount of circular structures is reproducible and practically no aggregates are formed. By comparison of cyclization experiments under defined conditions it is demonstrated that individual satellite components differ in the amount of circular structures formed during reassociation and in the distribution of linear and circular molecules. From the distribution of the contour lengths of circular molecules we conclude that the length of the repetitive sequence decreases with increasing buoyant density of the satellite components. The average lengths of the repetitive sequences calculated from electron microscopy measurements are in good agreement with those from renaturation kinetics."}
{"id": "PMID:235996", "title": "The conversion of glyceraldehyde-3-phosphate dehydrogenase to an acylphosphatase by trinitroglycerin and inactivation of this activity by azide and ascorbate.", "content": "Trinitroglycerin oxidizes the essential sulfhydryl group, Cys-149, of pig muscle glyceraldehyde-3-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate : NAD+ oxidoreductase(phosphorylating) EC 1.2.1.12) TO A SLUFENIC ACID, NOT TO A DISULFIDE. This conclusion is based on the observation that the inactivation of the dehydrogenase activity of the enzyme by the organic nitrate induces the acylphosphatase activity which is catalyzed by the sulfenic acid form of the enzyme. Inorganic nitrite is released during this process which is stoichiometric with the degree of inactivation of the dehydrogenase. The acylphosphatase activity induced by trinitroglycerin, unlike the dehydrogenase activity, is sensitive to CN-. Treatment of the enzyme oxidized with trinitroglycerin with 14-CN- leads to the incorporation of protein-bound 14-CN-, which is stoichiometric with the degree of inactivation of the dehydrogenase. Treatment of the sulfenic acid form of glyceraldehyde-3-phosphate dehydrogenase at pH 5.3 with a 10-fold molar excess of azide over the concentration of enzyme subunit completely inactivates the acylphosphatase reaction catalyzed by the oxidized enzyme. Concomitantly, the dehydrogenase activity catalyzed by the sulfhydryl form of the enzyme reappears which indicates that excess azide reduces the sulfenic acid which is required for the acylphosphatase. Treatment of the oxidized enzyme with a stoichiometric amount of azide at pH 5.3 stimulates the acylphosphatase activity and does not lead to the reappearance of dehydrogenase activity. When the sulfenic acid form of the enzyme is incubated with 20 mM L-ascorbate at pH 5.3, the acylphosphatase activity is completely inactivated and the dehydrogenase activity catalyzed by the reduced form of the enzyme is recovered. Thus, L-ascorbate also reduces the protein sulfenic acid which is required for the acylphosphatase activity.", "contents": "The conversion of glyceraldehyde-3-phosphate dehydrogenase to an acylphosphatase by trinitroglycerin and inactivation of this activity by azide and ascorbate. Trinitroglycerin oxidizes the essential sulfhydryl group, Cys-149, of pig muscle glyceraldehyde-3-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate : NAD+ oxidoreductase(phosphorylating) EC 1.2.1.12) TO A SLUFENIC ACID, NOT TO A DISULFIDE. This conclusion is based on the observation that the inactivation of the dehydrogenase activity of the enzyme by the organic nitrate induces the acylphosphatase activity which is catalyzed by the sulfenic acid form of the enzyme. Inorganic nitrite is released during this process which is stoichiometric with the degree of inactivation of the dehydrogenase. The acylphosphatase activity induced by trinitroglycerin, unlike the dehydrogenase activity, is sensitive to CN-. Treatment of the enzyme oxidized with trinitroglycerin with 14-CN- leads to the incorporation of protein-bound 14-CN-, which is stoichiometric with the degree of inactivation of the dehydrogenase. Treatment of the sulfenic acid form of glyceraldehyde-3-phosphate dehydrogenase at pH 5.3 with a 10-fold molar excess of azide over the concentration of enzyme subunit completely inactivates the acylphosphatase reaction catalyzed by the oxidized enzyme. Concomitantly, the dehydrogenase activity catalyzed by the sulfhydryl form of the enzyme reappears which indicates that excess azide reduces the sulfenic acid which is required for the acylphosphatase. Treatment of the oxidized enzyme with a stoichiometric amount of azide at pH 5.3 stimulates the acylphosphatase activity and does not lead to the reappearance of dehydrogenase activity. When the sulfenic acid form of the enzyme is incubated with 20 mM L-ascorbate at pH 5.3, the acylphosphatase activity is completely inactivated and the dehydrogenase activity catalyzed by the reduced form of the enzyme is recovered. Thus, L-ascorbate also reduces the protein sulfenic acid which is required for the acylphosphatase activity."}
{"id": "PMID:235997", "title": "Thymidylate synthetase from Diplococcus pneumoniae, properties and inhibition by folate analogs.", "content": "Thymidilate synthetase (methylenetetrahydrofolate:dUMP C-methyltransferase) in crude extract from Diplococcus pneumoniae exhibits a partial but variable requirement for Mg-2+ depending upon the buffer. Optimum Mg-2+ concentration is between 0.014 and 0.02 M. The optimum pH for activity in a variety of buffers occurred as a broad peak between 7.0 and 7.7. In Tris/acetate buffer, but not in potassium phosphate buffer, the pH optimum was different in the presence and absence of Mg-2+. Methylation of uridylate, cytidylate and deoxycytidylate could not be demonstrated over a pH range of 5.0-8.0. The enzyme exhibited an apparent Km for deoxyuridylate of 3.08 - 10-5 M and an apparent Km for L-(+)(minus)-5,10-methylene tetrahydrofolate of 2.66 - 10-4 M. During molecular-sieve chromatography and sucrose density-gradient centrifugation, the enzyme was detectable only as a single catalytically active form of Mr 34 000-38 000. 2,4-Diamino quinazoline antifolates were better competitive inhibitors (Ki = 3-8 -10-6 M) of thymidylate synthetase than 2,4-diamino pteridines (Ki = 3- 10-5 M). 2-Amino-4-hydroxy-quinazolines were the best inhibitors (Ki = 1.3-2.9 - 10-6 M). All of the 2,4-diamino quinazolines and pteridines inhibited dihydrofolate reductase from D. pneumoniae in a nearly stoichiometric fashion (Ki = less than 10-10 M). The 2-amino-4-hydroxy-quinazolines were poor inhibitors of this enzyme (Ki = 10=5 M).", "contents": "Thymidylate synthetase from Diplococcus pneumoniae, properties and inhibition by folate analogs. Thymidilate synthetase (methylenetetrahydrofolate:dUMP C-methyltransferase) in crude extract from Diplococcus pneumoniae exhibits a partial but variable requirement for Mg-2+ depending upon the buffer. Optimum Mg-2+ concentration is between 0.014 and 0.02 M. The optimum pH for activity in a variety of buffers occurred as a broad peak between 7.0 and 7.7. In Tris/acetate buffer, but not in potassium phosphate buffer, the pH optimum was different in the presence and absence of Mg-2+. Methylation of uridylate, cytidylate and deoxycytidylate could not be demonstrated over a pH range of 5.0-8.0. The enzyme exhibited an apparent Km for deoxyuridylate of 3.08 - 10-5 M and an apparent Km for L-(+)(minus)-5,10-methylene tetrahydrofolate of 2.66 - 10-4 M. During molecular-sieve chromatography and sucrose density-gradient centrifugation, the enzyme was detectable only as a single catalytically active form of Mr 34 000-38 000. 2,4-Diamino quinazoline antifolates were better competitive inhibitors (Ki = 3-8 -10-6 M) of thymidylate synthetase than 2,4-diamino pteridines (Ki = 3- 10-5 M). 2-Amino-4-hydroxy-quinazolines were the best inhibitors (Ki = 1.3-2.9 - 10-6 M). All of the 2,4-diamino quinazolines and pteridines inhibited dihydrofolate reductase from D. pneumoniae in a nearly stoichiometric fashion (Ki = less than 10-10 M). The 2-amino-4-hydroxy-quinazolines were poor inhibitors of this enzyme (Ki = 10=5 M)."}
{"id": "PMID:235998", "title": "Udp-galactose: glycoprotein galactosyltransferase activity in a clonal line of rat brain.", "content": "1. UDPgalactose:glycoprotein galactosyltransferase (EC 2.4.1.-) activity was demonstrated in homogenates from whole rat brain, isolated neuromal perikarya, enriched glial cell fractions, and cultured rat glial tumor cells (clone C6).  2. Galactosyltransferase activity was enriched 3-9-fold in neuronal perikarya and 1.4--1.8-fold in the glial cell fraction over the activity in whole brains from 19- and 40-day-old rats.  The activity of galactosyltransferase in neuronal perikarya decreased with age.  Extensive contamination of the glial cell fraction with membranous fragments appeared to obscure the precise specific activity of this fraction.  3. The specific activity of the enzyme in glial tumor cells was 4--8-fold higher than in brain tissue when the enzyme was assayed under identical conditions using endogenous and different exogenous acceptors.  4. Galactosyltransferase activities from adult brain and glial tumor cells had similar properties.  They both required Mn-2 plus and Triton, and exhibited pH optima between 5 and 7.  The apparent Km of the enzyme for UDPgalactose was 1.3-10-minus 4 M for brain tissue and 2.2-10-minus 4 M for glial tumor cells.  5. The high galactosyltransferase activity in glial tumor cells and in neuronal perikarya of younger rats is compatible with the possibility of a role of this enzyme in developing brain.", "contents": "Udp-galactose: glycoprotein galactosyltransferase activity in a clonal line of rat brain. 1. UDPgalactose:glycoprotein galactosyltransferase (EC 2.4.1.-) activity was demonstrated in homogenates from whole rat brain, isolated neuromal perikarya, enriched glial cell fractions, and cultured rat glial tumor cells (clone C6).  2. Galactosyltransferase activity was enriched 3-9-fold in neuronal perikarya and 1.4--1.8-fold in the glial cell fraction over the activity in whole brains from 19- and 40-day-old rats.  The activity of galactosyltransferase in neuronal perikarya decreased with age.  Extensive contamination of the glial cell fraction with membranous fragments appeared to obscure the precise specific activity of this fraction.  3. The specific activity of the enzyme in glial tumor cells was 4--8-fold higher than in brain tissue when the enzyme was assayed under identical conditions using endogenous and different exogenous acceptors.  4. Galactosyltransferase activities from adult brain and glial tumor cells had similar properties.  They both required Mn-2 plus and Triton, and exhibited pH optima between 5 and 7.  The apparent Km of the enzyme for UDPgalactose was 1.3-10-minus 4 M for brain tissue and 2.2-10-minus 4 M for glial tumor cells.  5. The high galactosyltransferase activity in glial tumor cells and in neuronal perikarya of younger rats is compatible with the possibility of a role of this enzyme in developing brain."}
{"id": "PMID:235999", "title": "Purification and characterization of a cyclic nucleotide-regulated 5'-nucleotidase from potatoe.", "content": "A procedure is presented for the rapid purification of a 5'-nucleotidase (5'-ribonucleotide phosphohydrolase, EC 3.1.3.5) from potato tubers, involving ammonium sulphate fractionation and chromatography on phosphocellulose, DEAE-cellulose and Sephadex G-75. Application of this procedure results in a 6000-fold purification of the 5'-nucleotidase and the final preparations are virtually homogeneous, yielding only one protein band on electrophorsis in polyacrylamide gels in non-dissociating or dissociating conditions. The 5'-nucleotidase has a molecular weight of 50 000 from gel filtration experiments. Sodium dodecylsulphate-polyacrylamide gel electrophoresis of the purified 5'-nucleotidase reveals one major band of molecular weight 25 000. The 5'-nucleotidase is competitively inhibited by cyclic nucleotides, having micromolar Ki values for cyclic AMP and cyclic GMP at pH 5.0 and pH 8.0. The enzyme has a pH optimum of 5.0 with 5'-GMP as substrate. While 5'-AMP and 3'-AMP are hydrolyzed at comparable rates at pH 5.0, at pH 8.0 the rate of hydrolysis of 3'-AMP is only 4% of that with 5'-AMP. ADP, ATP and 2'-AMP are very poor substrates for the enzyme. The nucleotidase has micromolar Km values for nucleoside 5'-monophosphates other than 5'-NMP. A wide variety of divalent cations activate the 5'-nucleotidase.", "contents": "Purification and characterization of a cyclic nucleotide-regulated 5'-nucleotidase from potatoe. A procedure is presented for the rapid purification of a 5'-nucleotidase (5'-ribonucleotide phosphohydrolase, EC 3.1.3.5) from potato tubers, involving ammonium sulphate fractionation and chromatography on phosphocellulose, DEAE-cellulose and Sephadex G-75. Application of this procedure results in a 6000-fold purification of the 5'-nucleotidase and the final preparations are virtually homogeneous, yielding only one protein band on electrophorsis in polyacrylamide gels in non-dissociating or dissociating conditions. The 5'-nucleotidase has a molecular weight of 50 000 from gel filtration experiments. Sodium dodecylsulphate-polyacrylamide gel electrophoresis of the purified 5'-nucleotidase reveals one major band of molecular weight 25 000. The 5'-nucleotidase is competitively inhibited by cyclic nucleotides, having micromolar Ki values for cyclic AMP and cyclic GMP at pH 5.0 and pH 8.0. The enzyme has a pH optimum of 5.0 with 5'-GMP as substrate. While 5'-AMP and 3'-AMP are hydrolyzed at comparable rates at pH 5.0, at pH 8.0 the rate of hydrolysis of 3'-AMP is only 4% of that with 5'-AMP. ADP, ATP and 2'-AMP are very poor substrates for the enzyme. The nucleotidase has micromolar Km values for nucleoside 5'-monophosphates other than 5'-NMP. A wide variety of divalent cations activate the 5'-nucleotidase."}
{"id": "PMID:236000", "title": "Epidermal nucleases: purification and characterization of ribonuclease from mammalian epidermis.", "content": "The major ribonuclease of adult guinea pig epidermis has been isolated and purfied over 1000-fold by a combination of ammonium sulfate fractionation, affinity and ion-exchange chromatography, and electrophoresis. The purified enzyme is free from phosphodiesterase and phosphatase activities. The ribonuclease is optimally active near neutrality in phosphate buffer, with a Km of 3mu g/ml toward [14-C]RNA from Erhlich ascites tumor cells. (here are no metal requirements for activity. The enzyme catalyzes the endonucleolytic hydrolysis of high molecular weight yeast RNA and it also hydrolyzes polycytidylic and polyuridylic acids, but not polyadenylic, polyguanylic, and polyinosinic acids. The apparent molecular weight of the active enzyme is 28 500.", "contents": "Epidermal nucleases: purification and characterization of ribonuclease from mammalian epidermis. The major ribonuclease of adult guinea pig epidermis has been isolated and purfied over 1000-fold by a combination of ammonium sulfate fractionation, affinity and ion-exchange chromatography, and electrophoresis. The purified enzyme is free from phosphodiesterase and phosphatase activities. The ribonuclease is optimally active near neutrality in phosphate buffer, with a Km of 3mu g/ml toward [14-C]RNA from Erhlich ascites tumor cells. (here are no metal requirements for activity. The enzyme catalyzes the endonucleolytic hydrolysis of high molecular weight yeast RNA and it also hydrolyzes polycytidylic and polyuridylic acids, but not polyadenylic, polyguanylic, and polyinosinic acids. The apparent molecular weight of the active enzyme is 28 500."}
{"id": "PMID:236001", "title": "Production of 1, 3-beta-glucanase by Bacillus No. 221.  An alkalophilic microorganism.", "content": "A 1, 3-beta-glucanase of Bacillus No. 221 has been extensively purified by a DEAE-cellulose column followed by a Sephadex G-75 gel filtration, and crystallized in ammonium sulfate solution.  The crystalline enzyme is homogenous on the basis of polyacrylamide gel electrophoresis, sedimentation in ultracentrifuge (3.2 S), Ampholine electrofocusing (pI=4.1) and dodecylsulfate-polyacrylamide gel electrophoresis (Mr=36 000). The enzyme has an optimum pH for enzyme action at 8.5 which is higher than those of other 1, 3-beta-glucanases so far reported.  The enzyme is very thermostable; about 90% of activity remains after being heated at 70 degrees C for 10 min, and no effect of Ca-2's obversed.  The enzyme does not hydrolyse laminaritriose, but hydrolyses laminaritetraose, and yields glucose and laminaritriose.  The enzyme splits laminaran at random and yields glucose, laminaribiose, laminaritriose and higher oligosaccharides.  From these results, this enzyme is a type of endo-1, 3-beta-glucanase.", "contents": "Production of 1, 3-beta-glucanase by Bacillus No. 221.  An alkalophilic microorganism. A 1, 3-beta-glucanase of Bacillus No. 221 has been extensively purified by a DEAE-cellulose column followed by a Sephadex G-75 gel filtration, and crystallized in ammonium sulfate solution.  The crystalline enzyme is homogenous on the basis of polyacrylamide gel electrophoresis, sedimentation in ultracentrifuge (3.2 S), Ampholine electrofocusing (pI=4.1) and dodecylsulfate-polyacrylamide gel electrophoresis (Mr=36 000). The enzyme has an optimum pH for enzyme action at 8.5 which is higher than those of other 1, 3-beta-glucanases so far reported.  The enzyme is very thermostable; about 90% of activity remains after being heated at 70 degrees C for 10 min, and no effect of Ca-2's obversed.  The enzyme does not hydrolyse laminaritriose, but hydrolyses laminaritetraose, and yields glucose and laminaritriose.  The enzyme splits laminaran at random and yields glucose, laminaribiose, laminaritriose and higher oligosaccharides.  From these results, this enzyme is a type of endo-1, 3-beta-glucanase."}
{"id": "PMID:236002", "title": "The regulation of myo-inositol-1-phosphate-synthase activity from Neurospora crassa by pyrophosphate and some cations.", "content": "The effect of several cations on the inhibition by PPi of the enzyme myo-inositol-1-phosphate synthase (1L-myo-inositol-1-phosphate lyase (isomerizing) EC 5.5.1.4) from Neurospora crassa was studied. The study wastol biosynthesis can occur in the presence of an intracellular PPi concentration which exceeds the Ki for the enzyme by 350-fold. The inhibition of enzyme activity by PPi,at pH 7.7, was reversed, in decreasing order of effectiveness, by Mn-2, Fe-3", "contents": "The regulation of myo-inositol-1-phosphate-synthase activity from Neurospora crassa by pyrophosphate and some cations. The effect of several cations on the inhibition by PPi of the enzyme myo-inositol-1-phosphate synthase (1L-myo-inositol-1-phosphate lyase (isomerizing) EC 5.5.1.4) from Neurospora crassa was studied. The study wastol biosynthesis can occur in the presence of an intracellular PPi concentration which exceeds the Ki for the enzyme by 350-fold. The inhibition of enzyme activity by PPi,at pH 7.7, was reversed, in decreasing order of effectiveness, by Mn-2, Fe-3"}
{"id": "PMID:236003", "title": "Protein kinases in brown adipose tissue of developing rats.  I. GTP as nucleotide substrate for histone phosphorylation.", "content": "100 000 times g soluble extracts from interscapular brown adipose tissue catalyzed the transfer of the terminal phosphoryl group from GTP to histone.  Maximal velocity was achieved only with both cyclic AMP and ATP present.  The cyclic AMP dose-response curve was the same as for the ATP-utilizing enzyme, with maximum stimulation at 0.5 muM.  ATP (1--100muM) increased the rate of histone phosphorylation with GTP as the radioactive substrate.  Higher concentrations had a dilution effect similar to that of GTP on the ATP-utilizing enzyme.  Similar effects were observed with ADP and AMP.  The apparent Km values for histone were the same with both GTP and ATP as nucleotide substrates.  The effects of pH, purified beef muscle kinase inhibitor and of NaCl were also the same.  Maximum velocities of histone phosphorylation from ATP and those from GTP were almost the same in brown fat of all age groups testes,  Separated on histone-Sepharose, the GTP-utilizing activity was absolutely dependent on the re-addition of the ATP-utilizing enzyme (a linear relationship with a slope of approx. 0.95).  An extremely active nucleotide phosphotransferase activity was found in the same subcellular fraction.  The rate of equilibration of the gamma-32-P between GTP and ATP could account for all the histone phosphorylation with [gamma-32-P] GTP.  It is concluded that, in spite of the presence of nucleotide phosphotransferase and ATP-protein kinase activities, a direct transfer from GTP to a protein substrate cannot be excluded.  Also, histone may not be the natural protein acceptor for GTP-linked phosphorylation.", "contents": "Protein kinases in brown adipose tissue of developing rats.  I. GTP as nucleotide substrate for histone phosphorylation. 100 000 times g soluble extracts from interscapular brown adipose tissue catalyzed the transfer of the terminal phosphoryl group from GTP to histone.  Maximal velocity was achieved only with both cyclic AMP and ATP present.  The cyclic AMP dose-response curve was the same as for the ATP-utilizing enzyme, with maximum stimulation at 0.5 muM.  ATP (1--100muM) increased the rate of histone phosphorylation with GTP as the radioactive substrate.  Higher concentrations had a dilution effect similar to that of GTP on the ATP-utilizing enzyme.  Similar effects were observed with ADP and AMP.  The apparent Km values for histone were the same with both GTP and ATP as nucleotide substrates.  The effects of pH, purified beef muscle kinase inhibitor and of NaCl were also the same.  Maximum velocities of histone phosphorylation from ATP and those from GTP were almost the same in brown fat of all age groups testes,  Separated on histone-Sepharose, the GTP-utilizing activity was absolutely dependent on the re-addition of the ATP-utilizing enzyme (a linear relationship with a slope of approx. 0.95).  An extremely active nucleotide phosphotransferase activity was found in the same subcellular fraction.  The rate of equilibration of the gamma-32-P between GTP and ATP could account for all the histone phosphorylation with [gamma-32-P] GTP.  It is concluded that, in spite of the presence of nucleotide phosphotransferase and ATP-protein kinase activities, a direct transfer from GTP to a protein substrate cannot be excluded.  Also, histone may not be the natural protein acceptor for GTP-linked phosphorylation."}
{"id": "PMID:236004", "title": "Glycolysis in human erythrocytes containing elevated concentrations of 2, 3-P2-glycerate.", "content": "In studies on the mechanism of the inhibitory effect of 2, 3-diphosphoglycerate on glycolysis in human erythrocytes, the following results were obtained: 1) Glucose consumption and lactate production are reduced by 70 and 40 per cent relative to normal erythrocytes in red blood cells containing five times the normal amount of 2, 3, -P2-glycerate (\"high-diphosphoglycerate\" cells) at an extracellular pH of 7.4. The marked dependency of glycolysis on the extracellular pH observed in normal erythrocytes is almost completely lost in the \"high-diphosphoglycerate\" cells.  2) About 50 per cent of the inhibition of glycolysis in \"high-diphosphoglycerate\" cells can be accounted for by the 2, 3-P2-glycerate-induced decrease of the red-cell pH.  This fall of the red-cell pH which occurs as a conswquence of the Donnan effect of the non-pentrating 2, 3-P2-glycerate anion leads to a reduction of the glycolytic rate due to the properties of the enzyme phosphofructokinase.  3) The remaining part of the inhibitory effect must be attributed to an inhibition by 2, 3-P2-glycerate of glycolytic enzymes.  From measurements of glycolytic rates and of the concentrations of glycolytic intermediates in the absence and presence of methylene blue it is concluded that the hexokinase reaction is inhibited by an elevation of 2, 3-P2-glycerate concentration in \"high-diphosphoglycerate\" cells suggests that also the enzyme pyruvate kinase is inhibited by 2, 3-P2-glycerate.  4) The dependencies of net-change of 2, 3-P2-glycerate concentration on the red-cell pH are identical in normal and \"high-diphosphoglycerate\" cells indicating that the balance between formation and decomposition of 2, 3-P2-glycerate is the same in erythrocytes with normal and very high compositions of 2, 3-P2-glycerate.", "contents": "Glycolysis in human erythrocytes containing elevated concentrations of 2, 3-P2-glycerate. In studies on the mechanism of the inhibitory effect of 2, 3-diphosphoglycerate on glycolysis in human erythrocytes, the following results were obtained: 1) Glucose consumption and lactate production are reduced by 70 and 40 per cent relative to normal erythrocytes in red blood cells containing five times the normal amount of 2, 3, -P2-glycerate (\"high-diphosphoglycerate\" cells) at an extracellular pH of 7.4. The marked dependency of glycolysis on the extracellular pH observed in normal erythrocytes is almost completely lost in the \"high-diphosphoglycerate\" cells.  2) About 50 per cent of the inhibition of glycolysis in \"high-diphosphoglycerate\" cells can be accounted for by the 2, 3-P2-glycerate-induced decrease of the red-cell pH.  This fall of the red-cell pH which occurs as a conswquence of the Donnan effect of the non-pentrating 2, 3-P2-glycerate anion leads to a reduction of the glycolytic rate due to the properties of the enzyme phosphofructokinase.  3) The remaining part of the inhibitory effect must be attributed to an inhibition by 2, 3-P2-glycerate of glycolytic enzymes.  From measurements of glycolytic rates and of the concentrations of glycolytic intermediates in the absence and presence of methylene blue it is concluded that the hexokinase reaction is inhibited by an elevation of 2, 3-P2-glycerate concentration in \"high-diphosphoglycerate\" cells suggests that also the enzyme pyruvate kinase is inhibited by 2, 3-P2-glycerate.  4) The dependencies of net-change of 2, 3-P2-glycerate concentration on the red-cell pH are identical in normal and \"high-diphosphoglycerate\" cells indicating that the balance between formation and decomposition of 2, 3-P2-glycerate is the same in erythrocytes with normal and very high compositions of 2, 3-P2-glycerate."}
{"id": "PMID:236005", "title": "Endogenous purine metabolism in the conidia of wild type and certain adenine mutants of Neurospora crassa. I. The nature of the reserve pools and pool utilization during adenine starvation.", "content": "Conidia of four adenine auxotrophs (ad 9, ad 3B, ad 8 and ad 4) of Neurospora crassa differ in their ability to germinate on adenine-deficient medium. A large percentage of the ad 9 and ad 3B mutant conidia germinate while those of ad 8 and ad 4 mutant do not. No correlation was found between the size of the conidial purine reserves and the conidial ability to germinate. In all the strains the major fraction of the conidial purine reserve pools was inosine. The ad 8 and ad 4 mutants are blocked after IMP formation in the adenine biosynthetic pathway and therefore cannot use the stored inosine for germination. Pool-utilization studies indicated that in all strains investigated some of the purine reserves were lost from the conidia during incubation. In the most readily germinating strain, ad 9, only small amounts of the purine pool were lost from the conidia and a large portion of the reserve pool was used for nucleic acid synthesis. The nature of the purine reserves present in the conidia, and the ability of the strains to prevent loss of the stored purines from the conidia appear to be among the factors influencing the conidial germination of the adenine mutants of N. crassa.", "contents": "Endogenous purine metabolism in the conidia of wild type and certain adenine mutants of Neurospora crassa. I. The nature of the reserve pools and pool utilization during adenine starvation. Conidia of four adenine auxotrophs (ad 9, ad 3B, ad 8 and ad 4) of Neurospora crassa differ in their ability to germinate on adenine-deficient medium. A large percentage of the ad 9 and ad 3B mutant conidia germinate while those of ad 8 and ad 4 mutant do not. No correlation was found between the size of the conidial purine reserves and the conidial ability to germinate. In all the strains the major fraction of the conidial purine reserve pools was inosine. The ad 8 and ad 4 mutants are blocked after IMP formation in the adenine biosynthetic pathway and therefore cannot use the stored inosine for germination. Pool-utilization studies indicated that in all strains investigated some of the purine reserves were lost from the conidia during incubation. In the most readily germinating strain, ad 9, only small amounts of the purine pool were lost from the conidia and a large portion of the reserve pool was used for nucleic acid synthesis. The nature of the purine reserves present in the conidia, and the ability of the strains to prevent loss of the stored purines from the conidia appear to be among the factors influencing the conidial germination of the adenine mutants of N. crassa."}
{"id": "PMID:236006", "title": "The mechanism of liver microsomal lipid peroxidation.", "content": "In the presence of Fe-3+ and complexing anions, the peroxidation of unsaturated liver microsomal lipid in both intact microsomes and in a model system containing extracted microsomal lipid can be promoted by either NADPH and NADPH : cytochrome c reductase or by xanthine and xanthine oxidase. Erythrocuprein effectively inhibits the activity promoted by xanthine and xanthine oxidase but produces much less inhibition of NADPH-dependent peroxidation. The singlet-oxygen trapping agent, 1, 3-diphenylisobenzofuran, had no effect on NADPH-dependent peroxidation but strongly inhibited the peroxidation promoted by xanthine and xanthine oxidase. NADPH-dependent lipid peroxidation was also shown to be unaffected by hydroxyl radical scavengers.. The addition of catalase had no effect on NADPH-dependent lipid peroxidation, but it significantly increased the rate of malondialdehyde formation in the reaction promoted by xanthine and xanthine oxidase. The results demonstrate that NADPH-dependent lipid peroxidation is promoted by a reaction mechanism which does not involve either superoxide, singlet oxygen, HOOH, or the hydroxyl radical. It is concluded that NADPH-dependent lipid peroxidation is initiated by the reduction of Fe-3+ followed by the decomposition of hydroperoxides to generate alkoxyl radicals. The initiation reaction may involve some form of the perferryl ion or other metal ion species generated during oxidation of Fe-2+ by oxygen.", "contents": "The mechanism of liver microsomal lipid peroxidation. In the presence of Fe-3+ and complexing anions, the peroxidation of unsaturated liver microsomal lipid in both intact microsomes and in a model system containing extracted microsomal lipid can be promoted by either NADPH and NADPH : cytochrome c reductase or by xanthine and xanthine oxidase. Erythrocuprein effectively inhibits the activity promoted by xanthine and xanthine oxidase but produces much less inhibition of NADPH-dependent peroxidation. The singlet-oxygen trapping agent, 1, 3-diphenylisobenzofuran, had no effect on NADPH-dependent peroxidation but strongly inhibited the peroxidation promoted by xanthine and xanthine oxidase. NADPH-dependent lipid peroxidation was also shown to be unaffected by hydroxyl radical scavengers.. The addition of catalase had no effect on NADPH-dependent lipid peroxidation, but it significantly increased the rate of malondialdehyde formation in the reaction promoted by xanthine and xanthine oxidase. The results demonstrate that NADPH-dependent lipid peroxidation is promoted by a reaction mechanism which does not involve either superoxide, singlet oxygen, HOOH, or the hydroxyl radical. It is concluded that NADPH-dependent lipid peroxidation is initiated by the reduction of Fe-3+ followed by the decomposition of hydroperoxides to generate alkoxyl radicals. The initiation reaction may involve some form of the perferryl ion or other metal ion species generated during oxidation of Fe-2+ by oxygen."}
{"id": "PMID:236007", "title": "Effect of chorionic gonadotropin, triamcinolone, progesterone and estrogen on enzymes of placenta and liver in rats.", "content": "The activity of several enzymes of regulatory importance for the pathways of glycolysis, gluconeogenesis and lipogenesis was investigated in the placenta and liver of pregnant rats and in the liver of non-pregnant female rats. The rats received daily hormonal treatments on Days 15 to 17 of pregnancy and enzyme activities were measured on Day 18. Chorionic gonadotropin induced minor changes in enzyme activity, apart from a decrease in the activity of hepatic enzymes of lipogenesis in non-pregnant rats. Triamcinolone induced a marked increase in enzymes of gluconeogenesis and a decrease in the activity of pyruvate kinase in the liver of pregnant and non-pregnant rats; in contrast, inverse changes in activity, these enzymes were observed in the placenta. This response in the placenta was considered to arise not from direct hormone effect, but from the accompanying hyperglycemia and hyperinsulinemia. Triamcinolone also increased the activity of hepatic acetyl-CoA carboxylase in pregnant and non-pregnant rats, whereas it reduced the activity of this enzyme in the placenta. Estrogen produced changes similar to those of triamcinolone in the liver and placenta, except that it depressed the activity of acetyl-CoA carboxylase in both tissues. Progesterone had little effect on placental and hepatic enzymes. In general, the changes induced by these hormones in the placenta affected fewer enzymes than in the liver, were less extensive in magnitude and not necessarily in the same direction as in the liver. This indicates that the regulatory placental enzymes are subject to specific control mechanisms not necessarily influenced by direct hormone action.", "contents": "Effect of chorionic gonadotropin, triamcinolone, progesterone and estrogen on enzymes of placenta and liver in rats. The activity of several enzymes of regulatory importance for the pathways of glycolysis, gluconeogenesis and lipogenesis was investigated in the placenta and liver of pregnant rats and in the liver of non-pregnant female rats. The rats received daily hormonal treatments on Days 15 to 17 of pregnancy and enzyme activities were measured on Day 18. Chorionic gonadotropin induced minor changes in enzyme activity, apart from a decrease in the activity of hepatic enzymes of lipogenesis in non-pregnant rats. Triamcinolone induced a marked increase in enzymes of gluconeogenesis and a decrease in the activity of pyruvate kinase in the liver of pregnant and non-pregnant rats; in contrast, inverse changes in activity, these enzymes were observed in the placenta. This response in the placenta was considered to arise not from direct hormone effect, but from the accompanying hyperglycemia and hyperinsulinemia. Triamcinolone also increased the activity of hepatic acetyl-CoA carboxylase in pregnant and non-pregnant rats, whereas it reduced the activity of this enzyme in the placenta. Estrogen produced changes similar to those of triamcinolone in the liver and placenta, except that it depressed the activity of acetyl-CoA carboxylase in both tissues. Progesterone had little effect on placental and hepatic enzymes. In general, the changes induced by these hormones in the placenta affected fewer enzymes than in the liver, were less extensive in magnitude and not necessarily in the same direction as in the liver. This indicates that the regulatory placental enzymes are subject to specific control mechanisms not necessarily influenced by direct hormone action."}
{"id": "PMID:236008", "title": "Dihydrothiamine-like substances as experimental artefacts.", "content": "Experimental controls have shown that the dihydrothiamine-like substance previously reported as isolated from animal tissues was an artefact. In addition, no evidence is found for the reduction of thiamine by NADH.", "contents": "Dihydrothiamine-like substances as experimental artefacts. Experimental controls have shown that the dihydrothiamine-like substance previously reported as isolated from animal tissues was an artefact. In addition, no evidence is found for the reduction of thiamine by NADH."}
{"id": "PMID:236009", "title": "Studies on fungal polysaccharide. XVII. A new glucuronan \"protuberic acid\" produced by a fungus Kobayashia nipponica.", "content": "A water-soluble glucuronan \"protuberic acid\", [alpha] 22-D minus 83.6 degrees, was isolated and purified from Kobayashia Nipponica, and its physicochemical properties were investigated. The purified protuberic acid was homogeneous as shown by zone electrophoresis, gel filtration over Sepharose 4B, and ultracentrifugation. The sedimentation coefficient was 1.8 S and its intrinsic viscosity was 1.1 dl/g. By gel filtration the molecular weight was estimated to be about 170 000. The results of periodate oxidation, methylation analysis, and partial acid hydrolysis indicated that this acidic polysaccharide has a linear structure of mainly 1, 4-linkages and containing an acid-labile linkage. Reduced protuberic acid, [alpha] 22-D minus 44 degrees, is also described.", "contents": "Studies on fungal polysaccharide. XVII. A new glucuronan \"protuberic acid\" produced by a fungus Kobayashia nipponica. A water-soluble glucuronan \"protuberic acid\", [alpha] 22-D minus 83.6 degrees, was isolated and purified from Kobayashia Nipponica, and its physicochemical properties were investigated. The purified protuberic acid was homogeneous as shown by zone electrophoresis, gel filtration over Sepharose 4B, and ultracentrifugation. The sedimentation coefficient was 1.8 S and its intrinsic viscosity was 1.1 dl/g. By gel filtration the molecular weight was estimated to be about 170 000. The results of periodate oxidation, methylation analysis, and partial acid hydrolysis indicated that this acidic polysaccharide has a linear structure of mainly 1, 4-linkages and containing an acid-labile linkage. Reduced protuberic acid, [alpha] 22-D minus 44 degrees, is also described."}
{"id": "PMID:236010", "title": "Studies on the mechanism of metabolic stimulation in polymorphonuclear leucocytes during phagocytosis. I. Evidence for superoxide anion involvement in the oxidation of NADPH2.", "content": "1. The oxidation of NADPH2 by leucocyte granules, as measured at acid pH in the presence of Mn-2+, was found to be inhibited by superoxide dismutase. 2. Omission of Mn-2+ markedly lowered the oxidase activity at acid pH, which was still inhibited by superoxide dismutase. 3. At alkaline pH the oxidase activity was lower than at acid pH. 4. During oxidation of NADPH2 by leucocyte granules, reduction of cytochrome c occurred which was partially inhibited by superoxide dismutase. 5. It was concluded that NADPH2 oxidation occurs through an enzymatic reaction and a nonenzymatic chain reaction. Superoxide anion (O-minus-2 and NADPH- free radical would be involved in the chain reaction. The differential sensitivity of NADPH2 oxidation to superoxide dismutase in different experimental conditions (see above 1, 2 and 3) was explained on the basis of changes in the properties of the chain reaction.", "contents": "Studies on the mechanism of metabolic stimulation in polymorphonuclear leucocytes during phagocytosis. I. Evidence for superoxide anion involvement in the oxidation of NADPH2. 1. The oxidation of NADPH2 by leucocyte granules, as measured at acid pH in the presence of Mn-2+, was found to be inhibited by superoxide dismutase. 2. Omission of Mn-2+ markedly lowered the oxidase activity at acid pH, which was still inhibited by superoxide dismutase. 3. At alkaline pH the oxidase activity was lower than at acid pH. 4. During oxidation of NADPH2 by leucocyte granules, reduction of cytochrome c occurred which was partially inhibited by superoxide dismutase. 5. It was concluded that NADPH2 oxidation occurs through an enzymatic reaction and a nonenzymatic chain reaction. Superoxide anion (O-minus-2 and NADPH- free radical would be involved in the chain reaction. The differential sensitivity of NADPH2 oxidation to superoxide dismutase in different experimental conditions (see above 1, 2 and 3) was explained on the basis of changes in the properties of the chain reaction."}
{"id": "PMID:236011", "title": "Studies on the mechanism of metabolic stimulation in polymorphonuclear leucocytes during phagocytosis. II. Presence of the NADPH2 oxidizing activity in a myeloperoxidase-deficient subject.", "content": "1. The biochemical properties of leucocytes from a myeloperoxidase-deficient subject were compared with those of leucocytes from healthy subjects. 2. Myleoperoxidase-deficient leucocytes responded to phagocytosis of heat-killed bacteria with increased respiration, increased oxidation of glucose through the hexose monophosphate shunt and increased production of H2O2 as normal leucocytes do. 3. The ability of granules isolated from myeloperoxidase-deficient leucocytes to oxidize nicotinamide coenzymes was comparable to that of granules isolated from normal leucocytes. 4. The results argue against the hypothesis that oxidation of NADPH2 in leucocytes is performed by myeloperoxidase.", "contents": "Studies on the mechanism of metabolic stimulation in polymorphonuclear leucocytes during phagocytosis. II. Presence of the NADPH2 oxidizing activity in a myeloperoxidase-deficient subject. 1. The biochemical properties of leucocytes from a myeloperoxidase-deficient subject were compared with those of leucocytes from healthy subjects. 2. Myleoperoxidase-deficient leucocytes responded to phagocytosis of heat-killed bacteria with increased respiration, increased oxidation of glucose through the hexose monophosphate shunt and increased production of H2O2 as normal leucocytes do. 3. The ability of granules isolated from myeloperoxidase-deficient leucocytes to oxidize nicotinamide coenzymes was comparable to that of granules isolated from normal leucocytes. 4. The results argue against the hypothesis that oxidation of NADPH2 in leucocytes is performed by myeloperoxidase."}
{"id": "PMID:236012", "title": "Metabolism of D-mannosamine in bovine thyroid gland slices.", "content": "1. The nature of the acid-soluble mannosamine intermediates was investigated in bovine thyroid gland slices after incubation with a tracer amount of [14C]mannosamine plus 10 mM carrier mannosamine. 2. These radioactive intermediates were separated by ion exchange, columns, characterized by paper chromatography and were identified as N-acetylmannosamine-6-P. The radioactivity associated with these acid-soluble compounds constituted about 17 percent of the added [14C]mannosamine. 3. [14C]Mannosamine was incorporated as sialic acid only into thyroglobulin.", "contents": "Metabolism of D-mannosamine in bovine thyroid gland slices. 1. The nature of the acid-soluble mannosamine intermediates was investigated in bovine thyroid gland slices after incubation with a tracer amount of [14C]mannosamine plus 10 mM carrier mannosamine. 2. These radioactive intermediates were separated by ion exchange, columns, characterized by paper chromatography and were identified as N-acetylmannosamine-6-P. The radioactivity associated with these acid-soluble compounds constituted about 17 percent of the added [14C]mannosamine. 3. [14C]Mannosamine was incorporated as sialic acid only into thyroglobulin."}
{"id": "PMID:236013", "title": "[Purification of human gastric glycoprotein and a study of its carbohydrate components (author's transl)].", "content": "Mucus was extracted from human gastric mucosa by homogenization in distilled water. The crude extract was purified from plasma, salivary and tissue contaminants by different steps involving chromatography on Sepharose 6B, Sepharose 2B and immunosorbents. The native glycoprotein so prepared was found to be immunologically pure; it migrated as a single band in acrylamide agarose gel electrophoresis at pH 8.6 and 3.5. The molecule exhibits blood group acitivity, contains 0.71 per cent sialic acid but no sulphate. The carbohydrate moiety contains glucosamine, galactosamine, fucose, galatose and mannose in the molar proportions 3: 1.95: 2.92:4.53:0.05.", "contents": "[Purification of human gastric glycoprotein and a study of its carbohydrate components (author's transl)]. Mucus was extracted from human gastric mucosa by homogenization in distilled water. The crude extract was purified from plasma, salivary and tissue contaminants by different steps involving chromatography on Sepharose 6B, Sepharose 2B and immunosorbents. The native glycoprotein so prepared was found to be immunologically pure; it migrated as a single band in acrylamide agarose gel electrophoresis at pH 8.6 and 3.5. The molecule exhibits blood group acitivity, contains 0.71 per cent sialic acid but no sulphate. The carbohydrate moiety contains glucosamine, galactosamine, fucose, galatose and mannose in the molar proportions 3: 1.95: 2.92:4.53:0.05."}
{"id": "PMID:236014", "title": "Bovine luteinizing hormone. Circular dichroism and thermal difference spectra.", "content": "The circular dichroism of bovine luteinizing hormone in the far ultraviolet (200-240 nm) and near ultraviolet (240-320 nm) is reported as a function of pH, reduction and denaturation. The significance of side-chain ellipticity in the native and fully randomised hormone is critically examined, using denatured and reduced ribonuclease and insulin as bases for comparison. Disulphide groups make no measurable contribution to the side-chain ellipticity. Judged by the spectra of the subunits both isolated and recombined, those treatments which promote subunit disociation without causing chain unfolding, reversibly decrease the ellipticity in the near ultra-violet with minimal effect in the far ultraviolet. Thermal perturbation difference spectroscopy of bovine luteinizing hormone and its subunits shows that, in common with the ovine and porcine hormones, there are two tyrosine residues located at the interface between the subunits and inaccessible to water. Only two or three of the five water-accessible tyrosine residues are reactive to N-acetylimidazole.", "contents": "Bovine luteinizing hormone. Circular dichroism and thermal difference spectra. The circular dichroism of bovine luteinizing hormone in the far ultraviolet (200-240 nm) and near ultraviolet (240-320 nm) is reported as a function of pH, reduction and denaturation. The significance of side-chain ellipticity in the native and fully randomised hormone is critically examined, using denatured and reduced ribonuclease and insulin as bases for comparison. Disulphide groups make no measurable contribution to the side-chain ellipticity. Judged by the spectra of the subunits both isolated and recombined, those treatments which promote subunit disociation without causing chain unfolding, reversibly decrease the ellipticity in the near ultra-violet with minimal effect in the far ultraviolet. Thermal perturbation difference spectroscopy of bovine luteinizing hormone and its subunits shows that, in common with the ovine and porcine hormones, there are two tyrosine residues located at the interface between the subunits and inaccessible to water. Only two or three of the five water-accessible tyrosine residues are reactive to N-acetylimidazole."}
{"id": "PMID:236015", "title": "Temperature and pH dependent changes of immunoglobulin G structure.", "content": "1. The temperature and pH functions of the myeloma IgG(K) conformation were studied by optical rotatory dispersion, circular dichroism, thermal perturbation difference spectroscopy, solvent perturbation difference spectroscopy, electrochemical iodination and difference adiabatic scanning microcalorimetry. 2. The IgG studied was found to be capable of a fully reversible structural change between pH 6.5 and 6.0. A transition occurring at low pH is accompanied by an increase of exposure of the chromophores to the solvent. 3. The \"alkaline state\" was found to be capable of a fully reversible S-like transition at temperatures between 25 and 35 degrees C. The changes occurring at the higher temperature are accompanied by the screening of 14-15 tyrosine residues and probably by a small increase in the helicity of the protein. These changes are not accompanied by an appreciable heat effect. The thermal denaturation of the \"alkaline state\" occurs only at 64 degrees C in the narrow temperature interval (3-4 degrees C). 4. The \"acid state\" is not accompanied by S-like transition at 25-35 degrees C. The thermal denaturation of the \"acid state\" occurs at 54 degrees C in the wide temperature interval (8-9 degrees C). 5. It was proposed that the ionisation of the invariant histidine residues situated in the \"cavity\" between the constant and variable domains causes the pH transition studied. The temperature changes in the interval 25-35 degrees C are explained by the alteration of the domains interposition. Similar alterations were investigated as a result of antigen-antibody reaction.", "contents": "Temperature and pH dependent changes of immunoglobulin G structure. 1. The temperature and pH functions of the myeloma IgG(K) conformation were studied by optical rotatory dispersion, circular dichroism, thermal perturbation difference spectroscopy, solvent perturbation difference spectroscopy, electrochemical iodination and difference adiabatic scanning microcalorimetry. 2. The IgG studied was found to be capable of a fully reversible structural change between pH 6.5 and 6.0. A transition occurring at low pH is accompanied by an increase of exposure of the chromophores to the solvent. 3. The \"alkaline state\" was found to be capable of a fully reversible S-like transition at temperatures between 25 and 35 degrees C. The changes occurring at the higher temperature are accompanied by the screening of 14-15 tyrosine residues and probably by a small increase in the helicity of the protein. These changes are not accompanied by an appreciable heat effect. The thermal denaturation of the \"alkaline state\" occurs only at 64 degrees C in the narrow temperature interval (3-4 degrees C). 4. The \"acid state\" is not accompanied by S-like transition at 25-35 degrees C. The thermal denaturation of the \"acid state\" occurs at 54 degrees C in the wide temperature interval (8-9 degrees C). 5. It was proposed that the ionisation of the invariant histidine residues situated in the \"cavity\" between the constant and variable domains causes the pH transition studied. The temperature changes in the interval 25-35 degrees C are explained by the alteration of the domains interposition. Similar alterations were investigated as a result of antigen-antibody reaction."}
{"id": "PMID:236016", "title": "Purification and properties of glutamate binding protein from the periplasmic space of Escherichia coli K-12.", "content": "Glutamate binding protein released from the periplasmic space of Escherichia coli K-12 by lysozyme-EDTA treatment was purified to homogeneity and its physical and chemical properties were studied. It is a basic protein with a pI of 9.1. Its molecular weight, determined in an analytical ultracentrifuge, and by gel filtration on Sephadex G-100 and dodecylsulphate acrylamide is 29 700, 27 800 and 32 000, respectively. The KD value for glutamate was 6.7 - 10- minus 6 M. L-Aspartate, reduced glutathione, G-glutamate-gamma-benzylester and L-glutamate-gamma-ethylester competitively inhibited glutamate binding with K-i; values of 7.8 - 10- minus 5, 1.1 - 10- minus 5, 1.0 - 10- minus 5 and 1.0 - 10- minus 5 M, respectively. Spheroplasts retained 40% of glutamate transport as compared to intact cells. The glutamate binding activity of a glutamate-utilizing strain (CS7), was 1.6 times as high as that of the glutamate non-utilizing parent strain (CS101). Similarly, the glutamate binding activity of a temperature conditional glutamate-utilizing mutant (CS2-TC) was 1.9 times higher when grown at the permissive temperature (42 degrees C) than when grown at the restrictive temperature (30 degrees C).", "contents": "Purification and properties of glutamate binding protein from the periplasmic space of Escherichia coli K-12. Glutamate binding protein released from the periplasmic space of Escherichia coli K-12 by lysozyme-EDTA treatment was purified to homogeneity and its physical and chemical properties were studied. It is a basic protein with a pI of 9.1. Its molecular weight, determined in an analytical ultracentrifuge, and by gel filtration on Sephadex G-100 and dodecylsulphate acrylamide is 29 700, 27 800 and 32 000, respectively. The KD value for glutamate was 6.7 - 10- minus 6 M. L-Aspartate, reduced glutathione, G-glutamate-gamma-benzylester and L-glutamate-gamma-ethylester competitively inhibited glutamate binding with K-i; values of 7.8 - 10- minus 5, 1.1 - 10- minus 5, 1.0 - 10- minus 5 and 1.0 - 10- minus 5 M, respectively. Spheroplasts retained 40% of glutamate transport as compared to intact cells. The glutamate binding activity of a glutamate-utilizing strain (CS7), was 1.6 times as high as that of the glutamate non-utilizing parent strain (CS101). Similarly, the glutamate binding activity of a temperature conditional glutamate-utilizing mutant (CS2-TC) was 1.9 times higher when grown at the permissive temperature (42 degrees C) than when grown at the restrictive temperature (30 degrees C)."}
{"id": "PMID:236017", "title": "Isoelectric focusing in layers of granulated gels. II. Preparative isoelectric focusing.", "content": "A method for preparative isoelectric focusing of 0.1-10 g amounts of proteins is described. For anticonvective stabilization of the pH gradient, layers of granulated gels (E.G. Sephadex or Bio-Gel) of variable length, width and thickness were used either on glass plates or in troughs. Load capacity, defined as the amount of protein per ml gel suspension, was determined to be 5-10 mg per ml for total protein, irrespective of the pH range of the carrier ampholytes. For single proteins load capacities of 0.25-1 mg per ml were found for pH 3-10 carrier ampholytes, and 2-4 mg per ml for narrow pH range ampholytes. Experiments on a quartz plate followed by densitometric evaluation in situ at 280 nm have demonstrated that it is possible to proceed from analytical thin-layer isoelectric focusing to preparative separations without loss of resolution, just by changing the dimension of the gel layer and increasing the protein load. Improved resolution which facilitates isolation of isoelectrically homegenious components could be achieved on a 40 cm long separation distance. The geometry of a layer is favourable to heat dissipation and this permits the use of high voltage gradients. Recovery of the focused proteins is high an elution simple. The efficiency of the method is illustrated by examples showing separations of single proteins and protein mixtures.", "contents": "Isoelectric focusing in layers of granulated gels. II. Preparative isoelectric focusing. A method for preparative isoelectric focusing of 0.1-10 g amounts of proteins is described. For anticonvective stabilization of the pH gradient, layers of granulated gels (E.G. Sephadex or Bio-Gel) of variable length, width and thickness were used either on glass plates or in troughs. Load capacity, defined as the amount of protein per ml gel suspension, was determined to be 5-10 mg per ml for total protein, irrespective of the pH range of the carrier ampholytes. For single proteins load capacities of 0.25-1 mg per ml were found for pH 3-10 carrier ampholytes, and 2-4 mg per ml for narrow pH range ampholytes. Experiments on a quartz plate followed by densitometric evaluation in situ at 280 nm have demonstrated that it is possible to proceed from analytical thin-layer isoelectric focusing to preparative separations without loss of resolution, just by changing the dimension of the gel layer and increasing the protein load. Improved resolution which facilitates isolation of isoelectrically homegenious components could be achieved on a 40 cm long separation distance. The geometry of a layer is favourable to heat dissipation and this permits the use of high voltage gradients. Recovery of the focused proteins is high an elution simple. The efficiency of the method is illustrated by examples showing separations of single proteins and protein mixtures."}
{"id": "PMID:236019", "title": "Platelet fibrinogen. Identity and initial observations on the mode of its degradation by plasmin.", "content": "Fibrinogen has been purified from human platelets. Platelet fibrinogen exhibits a characteristic pattern in agar gel immunoelectrophoresis different from that of plasma fibrinogen. Stepwise plasmin degradation has been used in further elucidation of the molecular properties of the platelet protein. Examination of comparative digests by immunologic and gel electrophoretic methods has revealed that (1) the platelet protein is more resistant to plasmin degradation, (2) the plasmin-produced fragments of platelet fibrinogen differ consistently from those of its plasma counterpart, and (3) platelet fibrinogen is different from fragment X of plasma fibrinogen. It is suggested that platelet fibrinogen may contribute to the stability of the thrombus.", "contents": "Platelet fibrinogen. Identity and initial observations on the mode of its degradation by plasmin. Fibrinogen has been purified from human platelets. Platelet fibrinogen exhibits a characteristic pattern in agar gel immunoelectrophoresis different from that of plasma fibrinogen. Stepwise plasmin degradation has been used in further elucidation of the molecular properties of the platelet protein. Examination of comparative digests by immunologic and gel electrophoretic methods has revealed that (1) the platelet protein is more resistant to plasmin degradation, (2) the plasmin-produced fragments of platelet fibrinogen differ consistently from those of its plasma counterpart, and (3) platelet fibrinogen is different from fragment X of plasma fibrinogen. It is suggested that platelet fibrinogen may contribute to the stability of the thrombus."}
{"id": "PMID:236020", "title": "On the reaction of papain and succinylpapin with diazo-1-H-tetrazole.", "content": "1. The reaction of papain and succinylpapain with diazo-1-H-tetrazole was investigated under different conditions. The extent of modification of the amino acids histidine, tyrosine, tryptophan and lysine was determined spectrophotometrically and/or by amino acid analysis. 2. Only one of the two histidine residues present in the enzyme reacts with diazo-1-H-tetrazole forming a monoazo derivative. The pH dependence of the coupling reaction reveals a normal pK of this reactive histidine. There are several arguments suggesting that this may be histidine 159 near the essential SH-group of papain. 3. All five tryptophan residues of the protein react with the diazonium ion below pH 7 forming a monoazo derivative with an absorption maximum at 370 nm, above pH 7 only four residues couple with diazo-1-H-tetrazole. The reaction of one tryptophan and one histidine are correlated as can be concluded from the pH dependence of the coupling rate of both amino acids and the parallel impairment of the catalytic acitivity. 4. 10-11 tyrosine residues out of 19 react with diazo-1-H-tetrazole to give bisazo compounds. 5 residues involved in hydrogen bridges form monoazo compounds. Only 12 tyrosines can be acylated by acetylimidazole. A relationship between the extent of modification of tyrosine and the activity of the enzyme could not be found.", "contents": "On the reaction of papain and succinylpapin with diazo-1-H-tetrazole. 1. The reaction of papain and succinylpapain with diazo-1-H-tetrazole was investigated under different conditions. The extent of modification of the amino acids histidine, tyrosine, tryptophan and lysine was determined spectrophotometrically and/or by amino acid analysis. 2. Only one of the two histidine residues present in the enzyme reacts with diazo-1-H-tetrazole forming a monoazo derivative. The pH dependence of the coupling reaction reveals a normal pK of this reactive histidine. There are several arguments suggesting that this may be histidine 159 near the essential SH-group of papain. 3. All five tryptophan residues of the protein react with the diazonium ion below pH 7 forming a monoazo derivative with an absorption maximum at 370 nm, above pH 7 only four residues couple with diazo-1-H-tetrazole. The reaction of one tryptophan and one histidine are correlated as can be concluded from the pH dependence of the coupling rate of both amino acids and the parallel impairment of the catalytic acitivity. 4. 10-11 tyrosine residues out of 19 react with diazo-1-H-tetrazole to give bisazo compounds. 5 residues involved in hydrogen bridges form monoazo compounds. Only 12 tyrosines can be acylated by acetylimidazole. A relationship between the extent of modification of tyrosine and the activity of the enzyme could not be found."}
{"id": "PMID:236021", "title": "Purification of a carboxypeptidase B-like enzyme from the starfish Dermasterias imbricata.", "content": "A carboxypeptidase B-like enzyme which catalyses the hydrolysis of synthetic esters of lysine and arginine has been isolated from the starfish Dermasterias imbricata. This carboxypeptidase B-like enzyme has a molecular weight of approximately 34 000 and shares this and other properties with bovine pancreatic carboxypeptidase B. The existence of zymogen for this activity in the pyloric caeca of the starfish is demonstrated. This zymogen has a molecular weight near 40 000 and appears to be analogous to other monomeric procarboxypeptidases B. The zymogen possesses an intrinsic low-level activity toward synthetic substrates of carboxypeptidase B and is activated by trypsin.", "contents": "Purification of a carboxypeptidase B-like enzyme from the starfish Dermasterias imbricata. A carboxypeptidase B-like enzyme which catalyses the hydrolysis of synthetic esters of lysine and arginine has been isolated from the starfish Dermasterias imbricata. This carboxypeptidase B-like enzyme has a molecular weight of approximately 34 000 and shares this and other properties with bovine pancreatic carboxypeptidase B. The existence of zymogen for this activity in the pyloric caeca of the starfish is demonstrated. This zymogen has a molecular weight near 40 000 and appears to be analogous to other monomeric procarboxypeptidases B. The zymogen possesses an intrinsic low-level activity toward synthetic substrates of carboxypeptidase B and is activated by trypsin."}
{"id": "PMID:236022", "title": "Interaction of amino acids with silver(I) ions.", "content": "The reactivity of silver(I) ions towards twenty amino acids has been studied in aqueous unbuffered solutions using an ion-selective electrode as a highly sensitive monitor. Contrary to general belief, silver ions are not completely specific for cysteine, but also react with lysine, arginine, methionine and, to a minor extent, cystine. Nevertheless the interaction with all of these species except cysteine is too weak to affect significantly the determination of thiol in proteins by the customary argentometric titration method. The possible origin of errors arising in such titrations is discussed.", "contents": "Interaction of amino acids with silver(I) ions. The reactivity of silver(I) ions towards twenty amino acids has been studied in aqueous unbuffered solutions using an ion-selective electrode as a highly sensitive monitor. Contrary to general belief, silver ions are not completely specific for cysteine, but also react with lysine, arginine, methionine and, to a minor extent, cystine. Nevertheless the interaction with all of these species except cysteine is too weak to affect significantly the determination of thiol in proteins by the customary argentometric titration method. The possible origin of errors arising in such titrations is discussed."}
{"id": "PMID:236023", "title": "Spectral properties of phosphopyridoxyl-Lys-7(-41)-ribonuclease A.", "content": "We have studied the spectral properties of RNAase A containing a phosphopyridoxyl residue at the epsilon-NH2 group of Lys-7 or Lys-14. The overall conformations of the native and modified enzymes were shown to be rather similar. All three proteins have similar circular dichroism spectra within the 220-300-nm region, and similar thermal transition temperatures. All the changes in the RNAase A molecule modified are located in close proximity to the alkylated lysine residue. The phosphopyridoxyl group of (P-Pxy)-epsilon-Lys-41-RNAase A is situated directly at the enzyme active site and is 25% butied in the protein globule. The P-pyridoxyl group of (P-Pxy)-epsilon-Lys-7-RNAase A was shown to be located in the vicinity of the active site and to be more exposed to the solvent. In the pyridoxyl phosphate absorption band, optical activity is induced in both proteins. Study of the pH dependence of the changes occurring in the circular dichroism and absorption spectra has shown that in the modified proteins, the pyridoxyl phosphate chromophore is rather sensitive to the ionic state of the surrounding medium and serves as a \"reporter\" group when the relationship between structure and function of the RNAase A active site is being investigated.", "contents": "Spectral properties of phosphopyridoxyl-Lys-7(-41)-ribonuclease A. We have studied the spectral properties of RNAase A containing a phosphopyridoxyl residue at the epsilon-NH2 group of Lys-7 or Lys-14. The overall conformations of the native and modified enzymes were shown to be rather similar. All three proteins have similar circular dichroism spectra within the 220-300-nm region, and similar thermal transition temperatures. All the changes in the RNAase A molecule modified are located in close proximity to the alkylated lysine residue. The phosphopyridoxyl group of (P-Pxy)-epsilon-Lys-41-RNAase A is situated directly at the enzyme active site and is 25% butied in the protein globule. The P-pyridoxyl group of (P-Pxy)-epsilon-Lys-7-RNAase A was shown to be located in the vicinity of the active site and to be more exposed to the solvent. In the pyridoxyl phosphate absorption band, optical activity is induced in both proteins. Study of the pH dependence of the changes occurring in the circular dichroism and absorption spectra has shown that in the modified proteins, the pyridoxyl phosphate chromophore is rather sensitive to the ionic state of the surrounding medium and serves as a \"reporter\" group when the relationship between structure and function of the RNAase A active site is being investigated."}
{"id": "PMID:236024", "title": "Calcium binding to intestinal goblet cell mucin.", "content": "1. Binding of Ca-2+ to goblet cell mucin of rat small intestine was studied using equilibrium dialysis against 0.01 M Tris/HCl buffer (pH 7.4) and tracer amounts of 45-CaCl2. Binding was found to reach saturation at a Ca free -2+ concentration of 0.1--1.0 mM, to be independent of temperature (4-37 degrees C), and to increase with increasing pH (5.0-8.7). At low concentrations of Ca free -2+ (smaller than 0.03 mM) the binding curve was sigmoidal, suggesting positive cooperativity of binding sites and a possible change in the tertiary structure of the mucin. Binding was markedly reduced, and sigmoidicity abolished, by removal of sialic acid from the mucin, or by adding 0.14 M NaCl to the dialysis medium. This latter finding suggests that, in vivo, other cations would compete for Ca-2+ binding ligands. 2. Under conditions mimicking those used for binding studies, CaCl2 (10- minus 5 M) was found to cause a small increase (0.03 units) in the absorbance of mucin solutions, especially in the ultraviolet region, possibly indicating increased light scattering. No change in the solubility of the mucin was observed after the addition of CaCl2 (10- minus 6-10- minus 4 M). A significant decrease in viscosity of the mucin was noted, however, with the addition of CaCl2 (10- minus 6-10- minus 2 M). Together with the binding data, these findings suggested that during binding, Ca-2+ combines with negative charges on goblet cell mucin (especially those of sialic acid carboxyl groups) and induces contraction or folding of the macromolecule which promotes cooperative cation binding. No evidence was obtained to suggest that CaCl2 caused precipitation, polymerization or gelation of the mucin in 0.01 M Tris/HCl.?", "contents": "Calcium binding to intestinal goblet cell mucin. 1. Binding of Ca-2+ to goblet cell mucin of rat small intestine was studied using equilibrium dialysis against 0.01 M Tris/HCl buffer (pH 7.4) and tracer amounts of 45-CaCl2. Binding was found to reach saturation at a Ca free -2+ concentration of 0.1--1.0 mM, to be independent of temperature (4-37 degrees C), and to increase with increasing pH (5.0-8.7). At low concentrations of Ca free -2+ (smaller than 0.03 mM) the binding curve was sigmoidal, suggesting positive cooperativity of binding sites and a possible change in the tertiary structure of the mucin. Binding was markedly reduced, and sigmoidicity abolished, by removal of sialic acid from the mucin, or by adding 0.14 M NaCl to the dialysis medium. This latter finding suggests that, in vivo, other cations would compete for Ca-2+ binding ligands. 2. Under conditions mimicking those used for binding studies, CaCl2 (10- minus 5 M) was found to cause a small increase (0.03 units) in the absorbance of mucin solutions, especially in the ultraviolet region, possibly indicating increased light scattering. No change in the solubility of the mucin was observed after the addition of CaCl2 (10- minus 6-10- minus 4 M). A significant decrease in viscosity of the mucin was noted, however, with the addition of CaCl2 (10- minus 6-10- minus 2 M). Together with the binding data, these findings suggested that during binding, Ca-2+ combines with negative charges on goblet cell mucin (especially those of sialic acid carboxyl groups) and induces contraction or folding of the macromolecule which promotes cooperative cation binding. No evidence was obtained to suggest that CaCl2 caused precipitation, polymerization or gelation of the mucin in 0.01 M Tris/HCl.?"}
{"id": "PMID:236025", "title": "Alpha-glucan phosphorylase from sweet potato: isolation and properties of the partially degraded enzyme.", "content": "Alpha-Glucan phosphorylase (EC 2.4.1.1.) was purified from sweet potato roots. Apparently homogeneous preparations obtained are partially degraded products from phosphorylase, as judged from the results of molecular weight determination, NH-2-termini analysis and pyridoxal-5'-P assay. Phosphorylase is shown to be degraded in the crude extract from sweet potato. The degradation is partly suppressed by EDTA and by salts and is accelerated by reducing agents. It is proposed that sweet potato phosphorylase in its intact form has a similar molecular structure and similar properties to the white potato enzyme. Both plant phosphorylases are preferentially cleaved by protease near the middle of their polypeptide chains without much loss of enzyme activity.", "contents": "Alpha-glucan phosphorylase from sweet potato: isolation and properties of the partially degraded enzyme. Alpha-Glucan phosphorylase (EC 2.4.1.1.) was purified from sweet potato roots. Apparently homogeneous preparations obtained are partially degraded products from phosphorylase, as judged from the results of molecular weight determination, NH-2-termini analysis and pyridoxal-5'-P assay. Phosphorylase is shown to be degraded in the crude extract from sweet potato. The degradation is partly suppressed by EDTA and by salts and is accelerated by reducing agents. It is proposed that sweet potato phosphorylase in its intact form has a similar molecular structure and similar properties to the white potato enzyme. Both plant phosphorylases are preferentially cleaved by protease near the middle of their polypeptide chains without much loss of enzyme activity."}
{"id": "PMID:236026", "title": "Phage T4 lysozyme. Physical properties and reversible unfolding.", "content": "Phage T4 lysozyme has been used extensively in studies of the genetic code. However, little work has been done on the characterization of the purified enzyme. Therefore, we determined the spectral properties of native T4 lysozyme and used these properties to follow the unfolding transition. The ultraviolet absorption spectrum and solvent perturbation difference spectrum indicate that the aromatic amino acids are extensively exposed to solvent. The CD and ORD spectra are characteristic of a high fraction of helix. Guanidine hydrochloride denaturation results show that over a T4 lysozyme concentration range of 0.07-1 g/l the c-m equals 2.7 M guanidine hydrochloride at pH 5 and that the transition is 100% reversible as judged by enzymatic assay and four different spectrophotometric criteria: CD at 295 nm, CD at 223 nm, fluorescence intensity at 350 nm and wavelength of maximum fluorescence. Guanidine hydrochloride denaturation at pH 2.5 was followed using fluorescence emission and has a c-m equals 1.7 M guanidine hydrochloride, indicating a strong pH dependence of chemical unfolding. Reversible thermal denaturation conditions were located at acid pH, 0.2 M NaCl, 10-4 M dithiothreitol and 10-6 M T4 lysozyme. The CD signal at 223 nm was used to measure the unfolding. Thermodynamic analysis of the thermal data showed an increase in T-m, increment H-unf and increment S-unf with increasing pH.", "contents": "Phage T4 lysozyme. Physical properties and reversible unfolding. Phage T4 lysozyme has been used extensively in studies of the genetic code. However, little work has been done on the characterization of the purified enzyme. Therefore, we determined the spectral properties of native T4 lysozyme and used these properties to follow the unfolding transition. The ultraviolet absorption spectrum and solvent perturbation difference spectrum indicate that the aromatic amino acids are extensively exposed to solvent. The CD and ORD spectra are characteristic of a high fraction of helix. Guanidine hydrochloride denaturation results show that over a T4 lysozyme concentration range of 0.07-1 g/l the c-m equals 2.7 M guanidine hydrochloride at pH 5 and that the transition is 100% reversible as judged by enzymatic assay and four different spectrophotometric criteria: CD at 295 nm, CD at 223 nm, fluorescence intensity at 350 nm and wavelength of maximum fluorescence. Guanidine hydrochloride denaturation at pH 2.5 was followed using fluorescence emission and has a c-m equals 1.7 M guanidine hydrochloride, indicating a strong pH dependence of chemical unfolding. Reversible thermal denaturation conditions were located at acid pH, 0.2 M NaCl, 10-4 M dithiothreitol and 10-6 M T4 lysozyme. The CD signal at 223 nm was used to measure the unfolding. Thermodynamic analysis of the thermal data showed an increase in T-m, increment H-unf and increment S-unf with increasing pH."}
{"id": "PMID:236027", "title": "Tryptophanase from Sphaerophorus funduliformis. Purification, molecular weight and subunit properties.", "content": "A crystalline tryptophanase can be obtained from extracts of Spaerophorus funduliformis using a heat treatment, hydroxyapatite chromatography and solubility in solutions of (NH4)2SO4 as a function of pH and temperature. The purified enzyme is homogeneous by several criteria. S. funduliformis tryptophanase has a specific activity of 11.5-13.5 and requires pyridoxal 5'-phosphate for enzymatic activity. Like other tryptophanases that have been studied, the S. funduliformis enzyme is a tetramer protein consisting of four apparently identical subunits. The native enzyme has a sedimentation coefficient of 11.2 S and a molecular weight of 244 000. In solutions of 5 M guanidine - HCl, 8 M urea, and sodium dodecylsulfate, at high pH or in the presence of thiols, the enzyme dissociates to 59 000 molecular weight species which are homogeneous by the criterion of weight. Peptide maps of the reduced holo-tryptophanase show one pyridoxal-containing peptide and, lacking agreement with the determined amino acid composition, suggest that the subunits of the enzyme contain a high degree of internal sequence homology.", "contents": "Tryptophanase from Sphaerophorus funduliformis. Purification, molecular weight and subunit properties. A crystalline tryptophanase can be obtained from extracts of Spaerophorus funduliformis using a heat treatment, hydroxyapatite chromatography and solubility in solutions of (NH4)2SO4 as a function of pH and temperature. The purified enzyme is homogeneous by several criteria. S. funduliformis tryptophanase has a specific activity of 11.5-13.5 and requires pyridoxal 5'-phosphate for enzymatic activity. Like other tryptophanases that have been studied, the S. funduliformis enzyme is a tetramer protein consisting of four apparently identical subunits. The native enzyme has a sedimentation coefficient of 11.2 S and a molecular weight of 244 000. In solutions of 5 M guanidine - HCl, 8 M urea, and sodium dodecylsulfate, at high pH or in the presence of thiols, the enzyme dissociates to 59 000 molecular weight species which are homogeneous by the criterion of weight. Peptide maps of the reduced holo-tryptophanase show one pyridoxal-containing peptide and, lacking agreement with the determined amino acid composition, suggest that the subunits of the enzyme contain a high degree of internal sequence homology."}
{"id": "PMID:236028", "title": "Thermodynamic and EPR characterization of mitochondrial succinate-cytochrome c reductase-phospholipid complexes.", "content": "Succinate-cytochrome c reductase can be easily solubilized in a phospholipid mixture (1:1, iysolecithin:lecithin) in the absence of detergents. The resulting solution contains two b cytochromes with half-reduction potentials of 95 plus or minus 10 mV (b561), and 0 plus or minus mV (566) and cytochrome c1 (Em7.2 equals +280 plus or minus 5 mV). The oxidation-reduction midpoint potentials obtained by optical potentiometric titrations are identical to those determined by the EPR titrations and are 40-60 mV higher than the corresponding midpoint potentials of these cytochromes in intact mitochondria. In contrast to detergent-suspended preparations, no CO-sensitive cytochrome b can be detected in the phospholipid-solubilized preparation or intact mitochondria. The half-reduction potential of cytochrome b566 is pH-dependent above pH 7.0 ( minus 60 mV/pH unit) while that of b561 is essentially pH-independent from pH 6.7-8.5, in contrast to its pH dependence in intact mitochondria. EPR characterizations show the presence of three oxidized low-spin heme-iron signals with g values of 3.78, 3.41 and 3.37. The identification of these signals with cytochromes b566(bT), b561 (bK) and c1 respectively is made on the basis of redox midpoint potentials. In addition, the preparation contains four distinct types of iron-sulfur centers: S1 and S2 (Em7.4 equals minus 260 mV and 0 mV), and two iron-sulfur proteins which are associated with the cytochrome b-c1 complex: Rieske's iron-sulfur protein (Em7.4 equals +280 mV) and Ohniski's Center 5 (Em7.4 equals +35 mV).", "contents": "Thermodynamic and EPR characterization of mitochondrial succinate-cytochrome c reductase-phospholipid complexes. Succinate-cytochrome c reductase can be easily solubilized in a phospholipid mixture (1:1, iysolecithin:lecithin) in the absence of detergents. The resulting solution contains two b cytochromes with half-reduction potentials of 95 plus or minus 10 mV (b561), and 0 plus or minus mV (566) and cytochrome c1 (Em7.2 equals +280 plus or minus 5 mV). The oxidation-reduction midpoint potentials obtained by optical potentiometric titrations are identical to those determined by the EPR titrations and are 40-60 mV higher than the corresponding midpoint potentials of these cytochromes in intact mitochondria. In contrast to detergent-suspended preparations, no CO-sensitive cytochrome b can be detected in the phospholipid-solubilized preparation or intact mitochondria. The half-reduction potential of cytochrome b566 is pH-dependent above pH 7.0 ( minus 60 mV/pH unit) while that of b561 is essentially pH-independent from pH 6.7-8.5, in contrast to its pH dependence in intact mitochondria. EPR characterizations show the presence of three oxidized low-spin heme-iron signals with g values of 3.78, 3.41 and 3.37. The identification of these signals with cytochromes b566(bT), b561 (bK) and c1 respectively is made on the basis of redox midpoint potentials. In addition, the preparation contains four distinct types of iron-sulfur centers: S1 and S2 (Em7.4 equals minus 260 mV and 0 mV), and two iron-sulfur proteins which are associated with the cytochrome b-c1 complex: Rieske's iron-sulfur protein (Em7.4 equals +280 mV) and Ohniski's Center 5 (Em7.4 equals +35 mV)."}
{"id": "PMID:236029", "title": "Delayed fluorescence from Rhodopseudomonas viridis following single flashes.", "content": "Delayed fluorescence from Rhodopseudomonas viridis membrane fragments has been studies using a phosphoroscope employing single, short actinic flashes, under conditions of controlled redox potential and temperature.  The emission spectrum shows that delayed fluorescence is emitted by the bulk, antenna bacteriochlorophyll.  The energy for delayed fluorescence, however, must be stored in a reaction-center complex including the photooxidized form (P+) of the primary electron-donor (P) and the photoreduced form (X MINUS) of the primary electron-acceptor.  This is shown by the following observations: (1) Delayed luminescence is quenched (a) at low redox potentials which allow cytochromes to reduce P+ rapidly after the flash, (b) at higher redox potentials which, by oxidizing P chemically, prevent the photochemical formation of P+X minus, and (c) upon transfer of an electron from X minus to a secondary acceptor, Y.  (2) Under conditions that prevent the reduction of P+ by cytochromes and the oxidation of X minus by Y, the decay kinetics of delayed fluorescence are identical with those of P+X minus, as measured from optical absorbance changes.  The main decay route for P+X minus under these conditions has a rate-constant of approximately 10-3-s-minus 1.  In contrase, a comparison of the intensities of delayed and prompt fluorescence indicates that the process in which P+X minus returns energy to the bulk bacteriochlorophyll has a rate-constant of 3.7 s-minus 1, at 295 degrees K and pH 7.8.  The decay kinetics of P+X minus and delayed fluorescence change little with temperature, whereas the intensity of delayed fluorescence increases with increasing temperature, having an activation energy of 12.5 kcal mol-mol- minus 1.  We conclude that the main decay route involves tunneling of an electron from X minus to P+, without the promotion of P to an excited state.  Delayed fluorescence requires such a promotion, followed by transfer of energy to the bulk bacteriochlorophyll, and this combination of events is rare.  The activation energy, taken with potentiometric data, indicates that the photochemical conversion of PX to P+X minus results in increases of both the energy and the entropy of the system, by 16.6 kcal-mol- minus 1 and 8.8 cal-mol- minus 1-deg- minus 1.  The intensity of delayed fluorescence depends strongly on the pH; the origin of this effect remains unclear.", "contents": "Delayed fluorescence from Rhodopseudomonas viridis following single flashes. Delayed fluorescence from Rhodopseudomonas viridis membrane fragments has been studies using a phosphoroscope employing single, short actinic flashes, under conditions of controlled redox potential and temperature.  The emission spectrum shows that delayed fluorescence is emitted by the bulk, antenna bacteriochlorophyll.  The energy for delayed fluorescence, however, must be stored in a reaction-center complex including the photooxidized form (P+) of the primary electron-donor (P) and the photoreduced form (X MINUS) of the primary electron-acceptor.  This is shown by the following observations: (1) Delayed luminescence is quenched (a) at low redox potentials which allow cytochromes to reduce P+ rapidly after the flash, (b) at higher redox potentials which, by oxidizing P chemically, prevent the photochemical formation of P+X minus, and (c) upon transfer of an electron from X minus to a secondary acceptor, Y.  (2) Under conditions that prevent the reduction of P+ by cytochromes and the oxidation of X minus by Y, the decay kinetics of delayed fluorescence are identical with those of P+X minus, as measured from optical absorbance changes.  The main decay route for P+X minus under these conditions has a rate-constant of approximately 10-3-s-minus 1.  In contrase, a comparison of the intensities of delayed and prompt fluorescence indicates that the process in which P+X minus returns energy to the bulk bacteriochlorophyll has a rate-constant of 3.7 s-minus 1, at 295 degrees K and pH 7.8.  The decay kinetics of P+X minus and delayed fluorescence change little with temperature, whereas the intensity of delayed fluorescence increases with increasing temperature, having an activation energy of 12.5 kcal mol-mol- minus 1.  We conclude that the main decay route involves tunneling of an electron from X minus to P+, without the promotion of P to an excited state.  Delayed fluorescence requires such a promotion, followed by transfer of energy to the bulk bacteriochlorophyll, and this combination of events is rare.  The activation energy, taken with potentiometric data, indicates that the photochemical conversion of PX to P+X minus results in increases of both the energy and the entropy of the system, by 16.6 kcal-mol- minus 1 and 8.8 cal-mol- minus 1-deg- minus 1.  The intensity of delayed fluorescence depends strongly on the pH; the origin of this effect remains unclear."}
{"id": "PMID:236030", "title": "On the stimulation of the light-induced proton uptake by uncoupling aminoacridine derivatives in spinach chloroplasts.", "content": "1. Light-induced proton uptake by spinach chloroplasts is enhanced several-fold by 9-(4-diethylamino-1-methylbutylamino)-6-chloro-2-methoxyacridine (atebrin).  This stimulation does not depend on the chlorophyll concentration.  The amount of extra protons taken up in the presence of atebrin is determined by the pKa values of atebrin and the pH of the incubation medium.  2. Both the stimulation of the proton uptake and the maximal binding capacity for atebrin is sensitive to uncouplers.  However, the ratio of bound to free atebrin does not depend on the presence of uncoupler up to the saturating atebrin concentration.  3. From simultanious kinetic measurements of atebrin fluorescence and proton movement it seems that after binding of the completely protonated atebrin the dye and the protons can move separately.  This can also be inferred from the spectral behaviour of atebrin in illuminated chloroplasts.  4. The stimulation of the proton uptake by atebrin does not depend on the presence of salts in the incubation medium.  However, the 'saturating' atebrin concentration increases strongly with increasing salt concentration in the medium.  5. It is concluded that the interaction of atebrin and other acridines with energized chloroplasts most likely occurs at the level of the membrane proper.  6. It is proposed that uncoupling by atebrin is a consequence of the creation of a high proton activity at the periphery of the thylakoid membrane, which opposes a proton gradient across the membrane.  The uncoupling by atebrin is not of the protonophoric type according to this mechanism.", "contents": "On the stimulation of the light-induced proton uptake by uncoupling aminoacridine derivatives in spinach chloroplasts. 1. Light-induced proton uptake by spinach chloroplasts is enhanced several-fold by 9-(4-diethylamino-1-methylbutylamino)-6-chloro-2-methoxyacridine (atebrin).  This stimulation does not depend on the chlorophyll concentration.  The amount of extra protons taken up in the presence of atebrin is determined by the pKa values of atebrin and the pH of the incubation medium.  2. Both the stimulation of the proton uptake and the maximal binding capacity for atebrin is sensitive to uncouplers.  However, the ratio of bound to free atebrin does not depend on the presence of uncoupler up to the saturating atebrin concentration.  3. From simultanious kinetic measurements of atebrin fluorescence and proton movement it seems that after binding of the completely protonated atebrin the dye and the protons can move separately.  This can also be inferred from the spectral behaviour of atebrin in illuminated chloroplasts.  4. The stimulation of the proton uptake by atebrin does not depend on the presence of salts in the incubation medium.  However, the 'saturating' atebrin concentration increases strongly with increasing salt concentration in the medium.  5. It is concluded that the interaction of atebrin and other acridines with energized chloroplasts most likely occurs at the level of the membrane proper.  6. It is proposed that uncoupling by atebrin is a consequence of the creation of a high proton activity at the periphery of the thylakoid membrane, which opposes a proton gradient across the membrane.  The uncoupling by atebrin is not of the protonophoric type according to this mechanism."}
{"id": "PMID:236031", "title": "A study on the membrane potential and pH gradient in chromatophores and intact cells of photosynthetic bacteria.", "content": "Generation of membrane potential (delta psi) and transmembrane pH difference (delta pH) was studied in PPi-energized chromatophores of Rhodospirillum rubrum by means of measurements of carotenoid and bacteriochlorophyll absorption changes, atebrin and 8-anilinonaphthalene-1-sulphonate fluorescence responses, and phenyldicarbaundecaborane transport.  The data obtained are consistent with the suggestion that carotenoid, bacteriochlorophyll and phenyldicarbaundecaborane responses are indicators of delta psi, while an atebrin response is an indicator of delta pH.  The fluorescence of 8-anilinonaphthalene-1-sulphonate is affected both by delta psi and delta pH.", "contents": "A study on the membrane potential and pH gradient in chromatophores and intact cells of photosynthetic bacteria. Generation of membrane potential (delta psi) and transmembrane pH difference (delta pH) was studied in PPi-energized chromatophores of Rhodospirillum rubrum by means of measurements of carotenoid and bacteriochlorophyll absorption changes, atebrin and 8-anilinonaphthalene-1-sulphonate fluorescence responses, and phenyldicarbaundecaborane transport.  The data obtained are consistent with the suggestion that carotenoid, bacteriochlorophyll and phenyldicarbaundecaborane responses are indicators of delta psi, while an atebrin response is an indicator of delta pH.  The fluorescence of 8-anilinonaphthalene-1-sulphonate is affected both by delta psi and delta pH."}
{"id": "PMID:236032", "title": "Phospholipase A activities in rat placentas of 14 days' gestation.", "content": "1. Homogenates and subcellular fractions of placentas obtained from rats on the 14th day of gestation were assayed for enzymes characteristic of various subcellular organelles. Based on these assays it seemed the placental lysosomes (acid phosphatase activity) were distributed equally among the subcellular particulate fractions and that the cytosol was not contaminated by mitochondria or microsomes. 2. The placental preparations were assayed for phospholipase A activity using 2-[14-C] phosphatidylethanolamine. We found phospholipases A with pH optima of 4.0, 7.0, and 8.5. These enzymes had Ca-2+ requirements and subcellular localizations similar to those reported for adult rat liver (Waite, M., Scherphof, G.L., Boshouivers, F.M.G. and van Deenen, L.L.M. (1969) J. Lipid Res. 10, 411.) 3. The majority of the placental phospholipase A activity was found in the cytosol. We think this activity represents enzyme(s) solubilized from the plasma membranes of placental cells and speculate that this enzyme may be active in a placental transport mechanism.", "contents": "Phospholipase A activities in rat placentas of 14 days' gestation. 1. Homogenates and subcellular fractions of placentas obtained from rats on the 14th day of gestation were assayed for enzymes characteristic of various subcellular organelles. Based on these assays it seemed the placental lysosomes (acid phosphatase activity) were distributed equally among the subcellular particulate fractions and that the cytosol was not contaminated by mitochondria or microsomes. 2. The placental preparations were assayed for phospholipase A activity using 2-[14-C] phosphatidylethanolamine. We found phospholipases A with pH optima of 4.0, 7.0, and 8.5. These enzymes had Ca-2+ requirements and subcellular localizations similar to those reported for adult rat liver (Waite, M., Scherphof, G.L., Boshouivers, F.M.G. and van Deenen, L.L.M. (1969) J. Lipid Res. 10, 411.) 3. The majority of the placental phospholipase A activity was found in the cytosol. We think this activity represents enzyme(s) solubilized from the plasma membranes of placental cells and speculate that this enzyme may be active in a placental transport mechanism."}
{"id": "PMID:236033", "title": "Metabolism of alkyldihydroxyacetone phosphate in rat brain.", "content": "Alkyldihydroxyacetone-P is the first detectable product in the biosynthetic pathway for ether-linked glycerolipids that eventually leads to the formation of ethanolamine plasmalogens, a major constituent of myelin. During early postnatal development, the specific activity of NADPH2:alkyldihydroxyacetone-P oxidoreductase in microsomes from rat brain is maximum at 4-5 days after birth, the time when the specific activity of the enzymes that synthesize alkyldihydroxyacetone-P also peaks. For the oxidoreductase assay, we developed a thin-layer chromatographic method that separates alkyldihydroxyacetone-P as the dinitrophenylhydrazine derivative from its reduced product (alkylglycerol-P), with excellent resolution. Phosphohydrolases associated with brain microsomes exhibit optimal pH maximums at 5.2-5.6 and 7.5-7.8 for all three substrates tested -- alkyldihydroxyacetone-P, alkylglycerol-P and alkylacylglycerol-P. Alkylglycerol-P was most readily dephosphorylated under all experimental conditions. The enzyme(s) that dephosphorylates alkyldihydroxyacetone-P and alkylglycerol-P have similar properties with respect to Mg-2+ or EDTA; with both substrates, Mg-2+ had no effect and EDTA was highly stimulatory. In contrast, EDTA strongly inhibited the dephosphorylation of alkylaclglycerol-P and although Mg-2+ (1 mM) appeared to be required for optimal activity, higher levels inhibited the reaction.", "contents": "Metabolism of alkyldihydroxyacetone phosphate in rat brain. Alkyldihydroxyacetone-P is the first detectable product in the biosynthetic pathway for ether-linked glycerolipids that eventually leads to the formation of ethanolamine plasmalogens, a major constituent of myelin. During early postnatal development, the specific activity of NADPH2:alkyldihydroxyacetone-P oxidoreductase in microsomes from rat brain is maximum at 4-5 days after birth, the time when the specific activity of the enzymes that synthesize alkyldihydroxyacetone-P also peaks. For the oxidoreductase assay, we developed a thin-layer chromatographic method that separates alkyldihydroxyacetone-P as the dinitrophenylhydrazine derivative from its reduced product (alkylglycerol-P), with excellent resolution. Phosphohydrolases associated with brain microsomes exhibit optimal pH maximums at 5.2-5.6 and 7.5-7.8 for all three substrates tested -- alkyldihydroxyacetone-P, alkylglycerol-P and alkylacylglycerol-P. Alkylglycerol-P was most readily dephosphorylated under all experimental conditions. The enzyme(s) that dephosphorylates alkyldihydroxyacetone-P and alkylglycerol-P have similar properties with respect to Mg-2+ or EDTA; with both substrates, Mg-2+ had no effect and EDTA was highly stimulatory. In contrast, EDTA strongly inhibited the dephosphorylation of alkylaclglycerol-P and although Mg-2+ (1 mM) appeared to be required for optimal activity, higher levels inhibited the reaction."}
{"id": "PMID:236034", "title": "Glycosphinoglipid beta-galactosidases of cultured mammalian cells. Characterization of the enzymes from mouse cell line lmtk and human Lesch-Nyhan fibroblasts.", "content": "Evidence is presented for the existence of three distinct mammalian glycosphingolipid beta-galactosidase responsible for the hydrolysis of galactosylceramide, lactosylceramide and GM1 gangliside, respectively. Activity toward the (L-3-H)galactose-labeled substrates differed with respect to pH optimum, thermostability, effect of NaCl and inhibition by glycosides and related glycosphinglpids. Comparison of these enzymic acitivites in cultured mouse cell line LMTK- and human beta-galactosiddases could probably be detected in future experiments with somatic cell hybrids (formed by the fusion of these two cell strains by specifically inhibiting activity of mouse origin.", "contents": "Glycosphinoglipid beta-galactosidases of cultured mammalian cells. Characterization of the enzymes from mouse cell line lmtk and human Lesch-Nyhan fibroblasts. Evidence is presented for the existence of three distinct mammalian glycosphingolipid beta-galactosidase responsible for the hydrolysis of galactosylceramide, lactosylceramide and GM1 gangliside, respectively. Activity toward the (L-3-H)galactose-labeled substrates differed with respect to pH optimum, thermostability, effect of NaCl and inhibition by glycosides and related glycosphinglpids. Comparison of these enzymic acitivites in cultured mouse cell line LMTK- and human beta-galactosiddases could probably be detected in future experiments with somatic cell hybrids (formed by the fusion of these two cell strains by specifically inhibiting activity of mouse origin."}
{"id": "PMID:236035", "title": "Intracellular pH of Thermoplasma acidophila.", "content": "Thermoplasma acidophila, a mycoplasma-like organism, was grown at 56 degrees C and pH 2. The intracellular pH of this organism is close to neutral as measured by the distribution of a radioactive weak organic acid, 5,5-dimethyl-2,4-oxazolidinedione, across the plasma membrane. The cell can maintain the pH gradient when subjected to heat or to metabolic inhibitors. Our experiments seem to indicate that a major portion of the pH gradient is not maintained by active processes, but rather by a Donnan potential across the cell membrane.", "contents": "Intracellular pH of Thermoplasma acidophila. Thermoplasma acidophila, a mycoplasma-like organism, was grown at 56 degrees C and pH 2. The intracellular pH of this organism is close to neutral as measured by the distribution of a radioactive weak organic acid, 5,5-dimethyl-2,4-oxazolidinedione, across the plasma membrane. The cell can maintain the pH gradient when subjected to heat or to metabolic inhibitors. Our experiments seem to indicate that a major portion of the pH gradient is not maintained by active processes, but rather by a Donnan potential across the cell membrane."}
{"id": "PMID:236036", "title": "Phosphate transport in Neurospora. Derepression of a high-affinity transport system during phosphorus starvation.", "content": "In addition to the constitutive, low-affinity phosphate-transport system described previously, Neurospora possesses a second, high-affinity system which is derepressed during phosphorus starvation. At pH 5.8, System ii has a K1/2 of about 3muM and a Jmax of 5.2 mmol/1 cell water per min. System ii reaches maximal activity after about 2 h of growth in phosphorus-free minimal medium. Its formation is blocked by cycloheximide and, once made, it appears to turn over rapidly. Addition of cycloheximide to fully derepressed cultures results in the decay of System ii with a t1/2 of 14 min, very similar to the turnoacteriol. 95, 959-966) for tryptophan transport in Neurospora. Thus, these transport systems appear to be regulated by a balance between synthesis and breakdown, as affected by intracellular pools of substrate or related compounds.", "contents": "Phosphate transport in Neurospora. Derepression of a high-affinity transport system during phosphorus starvation. In addition to the constitutive, low-affinity phosphate-transport system described previously, Neurospora possesses a second, high-affinity system which is derepressed during phosphorus starvation. At pH 5.8, System ii has a K1/2 of about 3muM and a Jmax of 5.2 mmol/1 cell water per min. System ii reaches maximal activity after about 2 h of growth in phosphorus-free minimal medium. Its formation is blocked by cycloheximide and, once made, it appears to turn over rapidly. Addition of cycloheximide to fully derepressed cultures results in the decay of System ii with a t1/2 of 14 min, very similar to the turnoacteriol. 95, 959-966) for tryptophan transport in Neurospora. Thus, these transport systems appear to be regulated by a balance between synthesis and breakdown, as affected by intracellular pools of substrate or related compounds."}
{"id": "PMID:236037", "title": "Observations on the binding of adenosine 3':5'-monophosphate to cell membrane fragments from ox cerebral cortex.", "content": "Microsomal or synaptosome membrane fragments from ox brain bind cyclic AMP with a pH optimum of 7.0. Scatchard analysis shows the presence of at least two binding sites. Cyclic GMP and cyclic IMP only inhibit binding at concentrations 5000 times that of cyclic AMP and even higher concentration ratios of ATP and AMP have no effect. Membrane fragments saturated with cyclic [3-H]AMP lost less than 7% of bound nucleotide on incubation at 0 degrees C for 45 min but lost 25 % in the same period in the presence of 10 muM non-radioactive cyclic AMP.", "contents": "Observations on the binding of adenosine 3':5'-monophosphate to cell membrane fragments from ox cerebral cortex. Microsomal or synaptosome membrane fragments from ox brain bind cyclic AMP with a pH optimum of 7.0. Scatchard analysis shows the presence of at least two binding sites. Cyclic GMP and cyclic IMP only inhibit binding at concentrations 5000 times that of cyclic AMP and even higher concentration ratios of ATP and AMP have no effect. Membrane fragments saturated with cyclic [3-H]AMP lost less than 7% of bound nucleotide on incubation at 0 degrees C for 45 min but lost 25 % in the same period in the presence of 10 muM non-radioactive cyclic AMP."}
{"id": "PMID:236038", "title": "Transcription and division inhibitors in the medium of stationary phase cultures of the slime mold Dictyostelium discoideum.", "content": "When cell-free medium of a stationary phase culture is added to an exponentially multiplying culture, it blocks further cell division and depresses the level of nuclear transcription. Furthermore, when cell-free medium of a stationary phase culture is added directly to an in vitro transcription system containing nuclei isolated from exponentially multiplying amebae, it completely inhibits \"late\" incorporation (20-60 min reaction time), which is predominantly alpha-amanitin resistant (ribosomal-like). The stationary phase medium however, affects neither \"early\" alpha-amanitin resistant incorporation (0-20 min reaction time) nor alpha-amanitin sensitive incorporation. Inhibition of late in vitro transcription is not due to a nucleotidase, nor is it due to changes in the pH, ionic strength, or osmolarity of the reaction mixture.", "contents": "Transcription and division inhibitors in the medium of stationary phase cultures of the slime mold Dictyostelium discoideum. When cell-free medium of a stationary phase culture is added to an exponentially multiplying culture, it blocks further cell division and depresses the level of nuclear transcription. Furthermore, when cell-free medium of a stationary phase culture is added directly to an in vitro transcription system containing nuclei isolated from exponentially multiplying amebae, it completely inhibits \"late\" incorporation (20-60 min reaction time), which is predominantly alpha-amanitin resistant (ribosomal-like). The stationary phase medium however, affects neither \"early\" alpha-amanitin resistant incorporation (0-20 min reaction time) nor alpha-amanitin sensitive incorporation. Inhibition of late in vitro transcription is not due to a nucleotidase, nor is it due to changes in the pH, ionic strength, or osmolarity of the reaction mixture."}
{"id": "PMID:236041", "title": "Purification and characterization of an endonuclease from calf thymus acting on irradiated DNA.", "content": "An endonuclease acting on DNA exposed to ultraviolet light or gamma-rays has been extensively purified from calf thymus. The enzyme has a pH optimum at pH 7.0-7.5, acts with equal efficiency in the presence of EDTA or divalent cations (Mg-2+ or Ca-2+), is inhibited by NaCl and tRNA and is inactivated by incubation at 50 degrees C. Its molecular weight, determined by Sephadex chromatography or sodium dodecylsulfate gel electrophoresis, is approx. 30 000. The enzyme catalyzes the formation of breaks with 5'-phosphate termini in double-stranded DNA irradiated with ultraviolet or gamma-rays. It does not act on unirradiated DNA or denatured DNA. Since in all these properties the enzymatic activity on ultraviolet- and gamma-irradiated DNA behaved similarly and since the two activities cochromatographed in all systems used during purification, we conclude that they are associated with the same protein. The site of action of the enzyme in ultraviolet-irradiated DNA is a photoproduct other than pyrimidine dimers. Such a photoproduct can also be induced by irradiation of the DNA in vivo, i.e. within the cells.", "contents": "Purification and characterization of an endonuclease from calf thymus acting on irradiated DNA. An endonuclease acting on DNA exposed to ultraviolet light or gamma-rays has been extensively purified from calf thymus. The enzyme has a pH optimum at pH 7.0-7.5, acts with equal efficiency in the presence of EDTA or divalent cations (Mg-2+ or Ca-2+), is inhibited by NaCl and tRNA and is inactivated by incubation at 50 degrees C. Its molecular weight, determined by Sephadex chromatography or sodium dodecylsulfate gel electrophoresis, is approx. 30 000. The enzyme catalyzes the formation of breaks with 5'-phosphate termini in double-stranded DNA irradiated with ultraviolet or gamma-rays. It does not act on unirradiated DNA or denatured DNA. Since in all these properties the enzymatic activity on ultraviolet- and gamma-irradiated DNA behaved similarly and since the two activities cochromatographed in all systems used during purification, we conclude that they are associated with the same protein. The site of action of the enzyme in ultraviolet-irradiated DNA is a photoproduct other than pyrimidine dimers. Such a photoproduct can also be induced by irradiation of the DNA in vivo, i.e. within the cells."}
{"id": "PMID:236042", "title": "The presence of collagenase in collagen preparations.", "content": "The frequently observed instability of neutral salt solutions of native collagen extracted from various sources and partially purified by standard procedures has been studied by disc electrophoresis in polyacrylamide gel and by electron microscopic examination of segment long spacing crystallites. The phenomenon has revealed time and temperature dependency, pH optima near neutrality, and inhibition by sodium EDTA and serummin addition, collagen breakdown has been found to be quantitatively related to the state of aggregation of the substrate, being more marked in reconstituted collagen gels than in collagen in solutionma typical pattern of animal collagenase degradation of native collagen into two fragments designated as TC-A and TC-B has been observed under certain conditions. It is concluded that the degradation of native collagen in neutral salt solution is due to a specific collagenase, and that this enzyme probably remains bound to collagen throughout the process of extraction and partial purification. Experiments with gelatin suggest that, in addition to collagenase, a nonspecific proteolytic activity may also be present in collagen preparations.", "contents": "The presence of collagenase in collagen preparations. The frequently observed instability of neutral salt solutions of native collagen extracted from various sources and partially purified by standard procedures has been studied by disc electrophoresis in polyacrylamide gel and by electron microscopic examination of segment long spacing crystallites. The phenomenon has revealed time and temperature dependency, pH optima near neutrality, and inhibition by sodium EDTA and serummin addition, collagen breakdown has been found to be quantitatively related to the state of aggregation of the substrate, being more marked in reconstituted collagen gels than in collagen in solutionma typical pattern of animal collagenase degradation of native collagen into two fragments designated as TC-A and TC-B has been observed under certain conditions. It is concluded that the degradation of native collagen in neutral salt solution is due to a specific collagenase, and that this enzyme probably remains bound to collagen throughout the process of extraction and partial purification. Experiments with gelatin suggest that, in addition to collagenase, a nonspecific proteolytic activity may also be present in collagen preparations."}
{"id": "PMID:236043", "title": "[Study of the cell walls of yeasts Rhodotorula. VI'nfluence of 2-hydroxybiphenyl on phosphatase activities of Rh. rubra (author's transl)].", "content": "The inhibition of acid phosphatase activity observed after culture of Rh. rubra in phosphate rich mediums is raised by the culture of this yeast in presence of 2-hydroxybiphenyl (OHph2). The cell wall alkaline phosphatase activity was inhibited by this derivative; When cultivated with OHph2 an intra and a more extracellular acid phosphatase activity appeared. The comparative studies of the two extracellular acid phosphatases secreted in the medium with or without the OHph2 show they have similar characteristics. They are eluated at the same time from Sephadex  G-200, DEAE- and CM-cellulose columns, and have the same Km. They are both glycoproteins, with the sugars forming the polyose fragment identical, but the enzyme secreted in the medium containing the OHph2 contains less sugar than the one secreted in the medium without OHph2. The appearance of this acid phosphatase activity was attributed to the alteration of the membrane glycosylating systems or to the important ultra structure modifications of the cell wall of Rh. rubra when this yeast is cultivated with OHph2.", "contents": "[Study of the cell walls of yeasts Rhodotorula. VI'nfluence of 2-hydroxybiphenyl on phosphatase activities of Rh. rubra (author's transl)]. The inhibition of acid phosphatase activity observed after culture of Rh. rubra in phosphate rich mediums is raised by the culture of this yeast in presence of 2-hydroxybiphenyl (OHph2). The cell wall alkaline phosphatase activity was inhibited by this derivative; When cultivated with OHph2 an intra and a more extracellular acid phosphatase activity appeared. The comparative studies of the two extracellular acid phosphatases secreted in the medium with or without the OHph2 show they have similar characteristics. They are eluated at the same time from Sephadex  G-200, DEAE- and CM-cellulose columns, and have the same Km. They are both glycoproteins, with the sugars forming the polyose fragment identical, but the enzyme secreted in the medium containing the OHph2 contains less sugar than the one secreted in the medium without OHph2. The appearance of this acid phosphatase activity was attributed to the alteration of the membrane glycosylating systems or to the important ultra structure modifications of the cell wall of Rh. rubra when this yeast is cultivated with OHph2."}
{"id": "PMID:236044", "title": "The interaction of cobalt (II) complexes with bovine apocarbonic anhydrase B.", "content": "The second-order rate constants for interaction of a number of cobalt(II) complexes (including the aquated ion) with bovine apocarbonic anhydrase have been measured at pH equal to 7.5, 25 degrees C and I equal 0.1 M. The ease of entry of cobalt decreases, in general, as the number of its coordinated watersdecreases. The highest complexes (bis or tris) do not react. The Mono cobalt(II) -8-quinolinol-5-sulfonate and, particularly, 8-quinolinol complexes react very much more rapidly with apoenzyme than does Co(H20)6-2+ ion. The results are discussed.", "contents": "The interaction of cobalt (II) complexes with bovine apocarbonic anhydrase B. The second-order rate constants for interaction of a number of cobalt(II) complexes (including the aquated ion) with bovine apocarbonic anhydrase have been measured at pH equal to 7.5, 25 degrees C and I equal 0.1 M. The ease of entry of cobalt decreases, in general, as the number of its coordinated watersdecreases. The highest complexes (bis or tris) do not react. The Mono cobalt(II) -8-quinolinol-5-sulfonate and, particularly, 8-quinolinol complexes react very much more rapidly with apoenzyme than does Co(H20)6-2+ ion. The results are discussed."}
{"id": "PMID:236045", "title": "Kinetics of iron and copper catalysis of ascorbate oxidation.", "content": "The effects of oxidant, pH and ligands on iron- and copper-catalyzed ascorbate oxidation have been examined. The formation of the catalyst-substrate complex is affected by pH, whereas oxidant affects its breakdown. With copper-ion catalysis, ligands inhibit competitively. With iron catalysis, on the other hand, for a series of aminopolycarboxylic ligands at neutral pH, formation of catalyst-substrate is favored by ligands which form more stable iron complexes. Decreased rates caused by changes in metal environment (ligand or pH) may result for competing activities (e.g., catalase activity competing with peroxidase activity). Evidence for a ternary complex (catalyst-substrate-oxidant) is presented.", "contents": "Kinetics of iron and copper catalysis of ascorbate oxidation. The effects of oxidant, pH and ligands on iron- and copper-catalyzed ascorbate oxidation have been examined. The formation of the catalyst-substrate complex is affected by pH, whereas oxidant affects its breakdown. With copper-ion catalysis, ligands inhibit competitively. With iron catalysis, on the other hand, for a series of aminopolycarboxylic ligands at neutral pH, formation of catalyst-substrate is favored by ligands which form more stable iron complexes. Decreased rates caused by changes in metal environment (ligand or pH) may result for competing activities (e.g., catalase activity competing with peroxidase activity). Evidence for a ternary complex (catalyst-substrate-oxidant) is presented."}
{"id": "PMID:236048", "title": "Quantitative magnetic resonance studies of manganese uptake by mitochondria.", "content": "The uptake of the paramagnetic ion manganese by rat liver mitochondria is studied by electron paramagnetic resonance (EPR) spectroscopy. Emphasis is placed on: (a) obtaining accurate EPR quantitation of intramitochondrial manganese fractions previously described (Gunter, T. E., and J. S.Puskin, 1972, Biophys. J. 12:625) (b) establishing competition for intramitochondrial binding between one of these fractions and calcium, (c) demonstrating the effects of substrate and ATP concentrations on each fraction observed through EPR, and (d) demonstrating the effect of inorganic phosphate (Pi) concentration and pH on each fraction.", "contents": "Quantitative magnetic resonance studies of manganese uptake by mitochondria. The uptake of the paramagnetic ion manganese by rat liver mitochondria is studied by electron paramagnetic resonance (EPR) spectroscopy. Emphasis is placed on: (a) obtaining accurate EPR quantitation of intramitochondrial manganese fractions previously described (Gunter, T. E., and J. S.Puskin, 1972, Biophys. J. 12:625) (b) establishing competition for intramitochondrial binding between one of these fractions and calcium, (c) demonstrating the effects of substrate and ATP concentrations on each fraction observed through EPR, and (d) demonstrating the effect of inorganic phosphate (Pi) concentration and pH on each fraction."}
{"id": "PMID:236049", "title": "The self-association of ATP: thermodynamics and geometry.", "content": "The concentration and temperature dependence of the self-association of ademosin-5'-triphosphate (ATP) in aqueous solution was studied by means of ultraviolet absorption spectroscopy and circular dichroism (CD). Of several possible models, a model was  indefinite linear self-association, in which each step has the same equilibrium constant, describes the data best. The two different methods lead within experimental error to the same thermodynamic parameters. At pH 8.7, IN 1 M Tris and 0.5 M 7gCl-2, we find deltaH-0 equals -5.1 kcal/mole and deltaS-0 equals -13.0 e.u. These values do not differ much from those found for the self-association of uncharged bases and nucleosides in  aqueous solution. The CD spectrum that results from the self-association is conservative and quite similar in shape to that observed for some stacked dinucleotides: it is interpreted as a first approximation within the framework of the exciton model.", "contents": "The self-association of ATP: thermodynamics and geometry. The concentration and temperature dependence of the self-association of ademosin-5'-triphosphate (ATP) in aqueous solution was studied by means of ultraviolet absorption spectroscopy and circular dichroism (CD). Of several possible models, a model was  indefinite linear self-association, in which each step has the same equilibrium constant, describes the data best. The two different methods lead within experimental error to the same thermodynamic parameters. At pH 8.7, IN 1 M Tris and 0.5 M 7gCl-2, we find deltaH-0 equals -5.1 kcal/mole and deltaS-0 equals -13.0 e.u. These values do not differ much from those found for the self-association of uncharged bases and nucleosides in  aqueous solution. The CD spectrum that results from the self-association is conservative and quite similar in shape to that observed for some stacked dinucleotides: it is interpreted as a first approximation within the framework of the exciton model."}
{"id": "PMID:236050", "title": "Nuclear Magnetic resonance quadrupole relaxation studies of chloride binding to the isolated hemoglobins from trout (Salmo irideus).", "content": "NMR studies of chloride binding to the main components of trout blood, Hb Trout I and Hb Trout IV, indicate that although the affinity of chloride is high for both hemoglobins, the characteristics of the binding process are markedly differnet. In Hb Trout IV chemical exchange at the chloride binding site(s) is fast and quadrupole effects determine the linewidth; chloride binding has a definite pH dependence, but there is no significant oxygen linkage. In contrast Hb Trout I represents a unique case of slow chemical exchange, which may depend on unusual stereoche mical characteristics of the chloride binding site; chloride binding is pH independent, but shows a significant oxygen linkage, which may be attributed to changes of the lifetime of chloride at the binding site. The chloride binding properties displayed by Hb Trout I and IV have been compared with those of normal and modified human hemoglobins and discussed in terms of the structural differences in the C- and N-terminal regions of the alpha- and beta-chains.", "contents": "Nuclear Magnetic resonance quadrupole relaxation studies of chloride binding to the isolated hemoglobins from trout (Salmo irideus). NMR studies of chloride binding to the main components of trout blood, Hb Trout I and Hb Trout IV, indicate that although the affinity of chloride is high for both hemoglobins, the characteristics of the binding process are markedly differnet. In Hb Trout IV chemical exchange at the chloride binding site(s) is fast and quadrupole effects determine the linewidth; chloride binding has a definite pH dependence, but there is no significant oxygen linkage. In contrast Hb Trout I represents a unique case of slow chemical exchange, which may depend on unusual stereoche mical characteristics of the chloride binding site; chloride binding is pH independent, but shows a significant oxygen linkage, which may be attributed to changes of the lifetime of chloride at the binding site. The chloride binding properties displayed by Hb Trout I and IV have been compared with those of normal and modified human hemoglobins and discussed in terms of the structural differences in the C- and N-terminal regions of the alpha- and beta-chains."}
{"id": "PMID:236051", "title": "Cation bindint to alpha-sl-casein B. A comparison of electrostatic models.", "content": "System characteristics which determine calcium binding to and subsequent proton release from alpha-sl-casein B are reported at pH 6.6 and [Na-plus] equal to 0.04, 0.0, and 0.16M. Values of protein solvation, G, site bound calcium, Ca,S, and net monomer charge, Z, permitted distributed charge models to be constructed. The models examined proved inadequate in that it was impossible to keep the dielectric constant, D, within acceptable limits and/or predict measured proton release. Three discrete charge models were constructed. At D equals 4, all three gave good agreement between predicted and experimental data as Ca, S increased. The known amino acid sequence was used to make rodlet models for the whole molecule andfor just the phosphate-containing acidic peptide portion. A comparison of these shows the electrostatic dominance of the acidic peptide and suggests that the electrostatic environment for the remainder of the binding sites is essentially constant as Ca, S increases during addition of calcium ion. The third discrete charge model bends the acidic peptide rodlet into a torus. In this case, data were matched with less assumed bond strain under conditions of high molecular charge than with the other two models. This indicates that conformation and association may be important factors to consider when constructing discrete charge models to calculate electrostatic free energy.", "contents": "Cation bindint to alpha-sl-casein B. A comparison of electrostatic models. System characteristics which determine calcium binding to and subsequent proton release from alpha-sl-casein B are reported at pH 6.6 and [Na-plus] equal to 0.04, 0.0, and 0.16M. Values of protein solvation, G, site bound calcium, Ca,S, and net monomer charge, Z, permitted distributed charge models to be constructed. The models examined proved inadequate in that it was impossible to keep the dielectric constant, D, within acceptable limits and/or predict measured proton release. Three discrete charge models were constructed. At D equals 4, all three gave good agreement between predicted and experimental data as Ca, S increased. The known amino acid sequence was used to make rodlet models for the whole molecule andfor just the phosphate-containing acidic peptide portion. A comparison of these shows the electrostatic dominance of the acidic peptide and suggests that the electrostatic environment for the remainder of the binding sites is essentially constant as Ca, S increases during addition of calcium ion. The third discrete charge model bends the acidic peptide rodlet into a torus. In this case, data were matched with less assumed bond strain under conditions of high molecular charge than with the other two models. This indicates that conformation and association may be important factors to consider when constructing discrete charge models to calculate electrostatic free energy."}
{"id": "PMID:236052", "title": "[The ultrastructure of the parietal cells of the stomach and their functional activity].", "content": "Submicroscopic changes in the parietal cells of the fundus were compared with the data of spot-film intragastric pH-metry of the same mucosal areas in 18 patients treated at the hospital in the department of therapeutic food deprivation. There were seen no changes in the ultrastructure of the parietal cells after a brief (36-hour) fasting when the pH of the mucous membrane failed to differ from the normal. With increased duration of food deprivation there occurred a gradual alkalinization of the gastric secretion and the pH of the gastric wall shifted from 2.02 after a 3-day food deprivation to 4.8-5.0 after fasting for 20 to 30 days. In accordance, there was a change in the ultrastructure of the parietal cells consisting in flattening and subsequent disappearance of tubulovesicles, a reduction of the lumina of the intracellular channels and shortening of microvilli. The results of comparison of the submicroscopic changes with the data of pH-metry indicated that such submicroscopic shifts corresponded co depression of the functional activity of the parietal cells.", "contents": "[The ultrastructure of the parietal cells of the stomach and their functional activity]. Submicroscopic changes in the parietal cells of the fundus were compared with the data of spot-film intragastric pH-metry of the same mucosal areas in 18 patients treated at the hospital in the department of therapeutic food deprivation. There were seen no changes in the ultrastructure of the parietal cells after a brief (36-hour) fasting when the pH of the mucous membrane failed to differ from the normal. With increased duration of food deprivation there occurred a gradual alkalinization of the gastric secretion and the pH of the gastric wall shifted from 2.02 after a 3-day food deprivation to 4.8-5.0 after fasting for 20 to 30 days. In accordance, there was a change in the ultrastructure of the parietal cells consisting in flattening and subsequent disappearance of tubulovesicles, a reduction of the lumina of the intracellular channels and shortening of microvilli. The results of comparison of the submicroscopic changes with the data of pH-metry indicated that such submicroscopic shifts corresponded co depression of the functional activity of the parietal cells."}
{"id": "PMID:236053", "title": "[The role of mast cells in vascular permeability disorders in rats subjected to immobilization stress].", "content": "Disturbances of vascular permeability were studied by the \"vascular labeling\" technique in the mesentry during the 24-hour immobilization of rats. Administration of dimebolin (an antihistaminic preparation) decreased the number of labeled vessels and labeling intensity. This effect was expressed in the presence of mast cells only and was accompanied by the mast cell degranulation. The authors suppose that the mast cells contain a substance preventing the disturbance of vascular permeability and released during degranulation. Such substance might be heparin. Experiments showed that small doses of heparin failed to produce such effect. These results allowed one to conclude that mast cells played a double role in the mechanisms of disturbance of vascular permeability during immobilization--the damaging (by the action of histamine and serotonine) and the protective (by the released heparin) action.", "contents": "[The role of mast cells in vascular permeability disorders in rats subjected to immobilization stress]. Disturbances of vascular permeability were studied by the \"vascular labeling\" technique in the mesentry during the 24-hour immobilization of rats. Administration of dimebolin (an antihistaminic preparation) decreased the number of labeled vessels and labeling intensity. This effect was expressed in the presence of mast cells only and was accompanied by the mast cell degranulation. The authors suppose that the mast cells contain a substance preventing the disturbance of vascular permeability and released during degranulation. Such substance might be heparin. Experiments showed that small doses of heparin failed to produce such effect. These results allowed one to conclude that mast cells played a double role in the mechanisms of disturbance of vascular permeability during immobilization--the damaging (by the action of histamine and serotonine) and the protective (by the released heparin) action."}
{"id": "PMID:236054", "title": "[Thymidylate synthetase in the antimesometrial and mesometrial portions of decidual tissue under normal conditions and following application of the antifolate preparation chloridine].", "content": "Specific activity of thymidylate synthetase (TMS) under normal conditions and after the action of pyrimethamine was investigated in antimesometrial (A) and mesometrial (M) parts of rat decidua. On the 9th-11th days of pregnancy specific activity of TMS in the A part proved to be higher than in the M part of decidua, and the former one reached its maximum by the 10th day. Specific activity of TMS in the M part decreased gradually from the 9th to 11th days of gestation. Pyrimethamine, applied on the 9th day of pregnancy caused a wave-like increase in the specific activity of TMS in the A part; this elevation was not so pronounced in the M part; A study of the physico-chemical properties of TMS from the decidua and the embryos of rats showed that the enzyme had a molecular weight of 58000, an optimal pH of 6.9, and could be quickly inactivated by heating.", "contents": "[Thymidylate synthetase in the antimesometrial and mesometrial portions of decidual tissue under normal conditions and following application of the antifolate preparation chloridine]. Specific activity of thymidylate synthetase (TMS) under normal conditions and after the action of pyrimethamine was investigated in antimesometrial (A) and mesometrial (M) parts of rat decidua. On the 9th-11th days of pregnancy specific activity of TMS in the A part proved to be higher than in the M part of decidua, and the former one reached its maximum by the 10th day. Specific activity of TMS in the M part decreased gradually from the 9th to 11th days of gestation. Pyrimethamine, applied on the 9th day of pregnancy caused a wave-like increase in the specific activity of TMS in the A part; this elevation was not so pronounced in the M part; A study of the physico-chemical properties of TMS from the decidua and the embryos of rats showed that the enzyme had a molecular weight of 58000, an optimal pH of 6.9, and could be quickly inactivated by heating."}
{"id": "PMID:236055", "title": "The effect of platelet concentrate storage temperature on adenine nucleotide metabolism.", "content": "The effect of platelet concentrate storage temperature (4 degrees C versus 22 degrees C) on platelet adenine nucleotide metabolism was studied. In general, levels of platelet ATP and ADP, the release reaction, and the metabolis nucleotide pool were best preserved for 72 hr by storage of concentrates at 4 degrees C. Storage of concentrates for 72 hr at 22 degrees C was occasionally associated with a pH decrease to less than 6.0, which is incompatible with platelet viability. When the pH fell below 6.0, there was a marked deterioration of platelet adenine nucleotide levels and the release reaction. The results for concentrates stored at 22 degrees C, with a final pH above 6.0, were not inferior to the results for those stored at 4 degrees C. The pH remained above 7.0 in all concentrates stored at 4 degrees C. The pH changes of platelet concentrates stored at 22 degrees C could not solely be attributed to platelet count, red cell count, or bacterial contamination. Storage at both temperatures was associated with conversion of ATP in the metabolic adenine nucleotide pool to hypoxanthine.", "contents": "The effect of platelet concentrate storage temperature on adenine nucleotide metabolism. The effect of platelet concentrate storage temperature (4 degrees C versus 22 degrees C) on platelet adenine nucleotide metabolism was studied. In general, levels of platelet ATP and ADP, the release reaction, and the metabolis nucleotide pool were best preserved for 72 hr by storage of concentrates at 4 degrees C. Storage of concentrates for 72 hr at 22 degrees C was occasionally associated with a pH decrease to less than 6.0, which is incompatible with platelet viability. When the pH fell below 6.0, there was a marked deterioration of platelet adenine nucleotide levels and the release reaction. The results for concentrates stored at 22 degrees C, with a final pH above 6.0, were not inferior to the results for those stored at 4 degrees C. The pH remained above 7.0 in all concentrates stored at 4 degrees C. The pH changes of platelet concentrates stored at 22 degrees C could not solely be attributed to platelet count, red cell count, or bacterial contamination. Storage at both temperatures was associated with conversion of ATP in the metabolic adenine nucleotide pool to hypoxanthine."}
{"id": "PMID:236059", "title": "Activation of histidine decarboxylase by H2-receptor blockade: mechanism of action.", "content": "1 Treatment with histamine H2-receptor antagonists, which inhibit basal acid secretion was found to activate rat stomach histidine decarboxylase. At the same time the serum gastrin concentration was greatly increased. 2 In antrectomized rats neither the enzyme activity nor the serum gastrin concentration was affected by the treatment. 3 In analogy with previous observations on other inhibitors of acid secretion we suggest that the H2-receptor antagonists stimulate gastrin release through their effect on acid secretion and that the raised serum gastrin level is responsible for the enzyme activation.", "contents": "Activation of histidine decarboxylase by H2-receptor blockade: mechanism of action. 1 Treatment with histamine H2-receptor antagonists, which inhibit basal acid secretion was found to activate rat stomach histidine decarboxylase. At the same time the serum gastrin concentration was greatly increased. 2 In antrectomized rats neither the enzyme activity nor the serum gastrin concentration was affected by the treatment. 3 In analogy with previous observations on other inhibitors of acid secretion we suggest that the H2-receptor antagonists stimulate gastrin release through their effect on acid secretion and that the raised serum gastrin level is responsible for the enzyme activation."}
{"id": "PMID:236060", "title": "Influence of histamine H1- and H2-receptor blockers on sympathetic vasodilator and vasoconstrictor responses in canine paw.", "content": "1 Vasodilator responses to histamine, bradykinin and sympathetic nerve stimulation were elicited in the perfused paw of dogs treated with bretylium (15-20 mg/kg) and atropine. The H2-receptor blocking agent, burimamide, when administered in the dose of 5 mg/kg intravenously and 4 mg intra-arterially did not depress significantly these vasodilator responses. The subsequent administration of tripelennamine in the dose of 2.5-5 mg/kg intravenously and 4 mg intra-arterially produced a significant blockade of the response to histamine and reduced the sustained vasodilator response to nerve stimulation. 2 In guanethidine-treated dogs, tripelennamine administered in the same dose following burimamide produced a blockade of the response to histamine comparable to that in the bretylium experiments, but decreased only the sustained vasodilator response to stimulation at 1 Hz. When the order of administration of the antihistamines was reversed in another group of guanethidine-treated dogs, tripelennamine had only a slight blocking effect on the response to histamine and did not affect the responses to nerve stimulation. Burimamide exerted a significant blocking effect on the response to histamine, but not to nerve stimulation. Another H2-receptor blocking agent, metiamide, when given after tripelennamine, also had a marked blocking effect on the response to histamine and almost abolished the vasodilator response to 4-methylhistamine, an H2-agonist. Nevertheless, even in the presence of this profound histamine blockade, the sustained vasodilator response to nerve stimulation remained unchanged. 3 In another group of experiments vasoconstrictor responses to exogenous noradrenaline and sympathetic stimulation were initially depressed by burimamide and later returned to control values. Tripelennamine increased these responses by its uptake blocking action. 4 It is concluded that the sustained vasodilator response is not antagonized by a specific antihistaminic action. The decrease in the sustained vasodilator response produced by antihistamines is produced attributable to potentiation of a residual adrenergic vasoconstricotr effect not completely blocked by bretylium.", "contents": "Influence of histamine H1- and H2-receptor blockers on sympathetic vasodilator and vasoconstrictor responses in canine paw. 1 Vasodilator responses to histamine, bradykinin and sympathetic nerve stimulation were elicited in the perfused paw of dogs treated with bretylium (15-20 mg/kg) and atropine. The H2-receptor blocking agent, burimamide, when administered in the dose of 5 mg/kg intravenously and 4 mg intra-arterially did not depress significantly these vasodilator responses. The subsequent administration of tripelennamine in the dose of 2.5-5 mg/kg intravenously and 4 mg intra-arterially produced a significant blockade of the response to histamine and reduced the sustained vasodilator response to nerve stimulation. 2 In guanethidine-treated dogs, tripelennamine administered in the same dose following burimamide produced a blockade of the response to histamine comparable to that in the bretylium experiments, but decreased only the sustained vasodilator response to stimulation at 1 Hz. When the order of administration of the antihistamines was reversed in another group of guanethidine-treated dogs, tripelennamine had only a slight blocking effect on the response to histamine and did not affect the responses to nerve stimulation. Burimamide exerted a significant blocking effect on the response to histamine, but not to nerve stimulation. Another H2-receptor blocking agent, metiamide, when given after tripelennamine, also had a marked blocking effect on the response to histamine and almost abolished the vasodilator response to 4-methylhistamine, an H2-agonist. Nevertheless, even in the presence of this profound histamine blockade, the sustained vasodilator response to nerve stimulation remained unchanged. 3 In another group of experiments vasoconstrictor responses to exogenous noradrenaline and sympathetic stimulation were initially depressed by burimamide and later returned to control values. Tripelennamine increased these responses by its uptake blocking action. 4 It is concluded that the sustained vasodilator response is not antagonized by a specific antihistaminic action. The decrease in the sustained vasodilator response produced by antihistamines is produced attributable to potentiation of a residual adrenergic vasoconstricotr effect not completely blocked by bretylium."}
{"id": "PMID:236062", "title": "EEG features of depressive and schizophrenic states.", "content": "A 25-year-old female patient with a psychotic illness lasting three months in which schizophrenia and depressive episodes occurred was studied by serial EEGs. These were coded, masked and rated in a set way without knowledge of the clinical state. It was found that the schizophrenic state was characterized by a decrease in the amount and poor organization of alpha activity, as well as the occurrence of paroxysmal phenomena in particular a typical spike and wave. In the depressive episode, alpha activity was prominentand only scanty paroxysmal features were seen. Using these criteria a series of EEGsfrom psychiatric patients were assessed 'blind' with a view to separating them into either a schizophrenic or a depressive category. This proved possible in 17 cases (9 depressive and 8 schizophrenic). In only two was the categorization completely misjudged. These results suggest that further detailed study of the EEG, possibly with computer analysis, combined with assessment of the behavioural state might not only yield useful diagnostic information but also lead to a better understanding of the underlying neurophysiological basis of certain mental disorders.", "contents": "EEG features of depressive and schizophrenic states. A 25-year-old female patient with a psychotic illness lasting three months in which schizophrenia and depressive episodes occurred was studied by serial EEGs. These were coded, masked and rated in a set way without knowledge of the clinical state. It was found that the schizophrenic state was characterized by a decrease in the amount and poor organization of alpha activity, as well as the occurrence of paroxysmal phenomena in particular a typical spike and wave. In the depressive episode, alpha activity was prominentand only scanty paroxysmal features were seen. Using these criteria a series of EEGsfrom psychiatric patients were assessed 'blind' with a view to separating them into either a schizophrenic or a depressive category. This proved possible in 17 cases (9 depressive and 8 schizophrenic). In only two was the categorization completely misjudged. These results suggest that further detailed study of the EEG, possibly with computer analysis, combined with assessment of the behavioural state might not only yield useful diagnostic information but also lead to a better understanding of the underlying neurophysiological basis of certain mental disorders."}
{"id": "PMID:236064", "title": "Acute reactions to urographic contrast media.", "content": "A prospective study of 3509 consecutive patients examined by excretion urography has been conducted to assess the incidence and significance of the untoward effects of urographic contrast media. Four compounds were used in doses containing 160 to 500 mg iodine/kg body weight. Toxic effects, arm pain, and allegic reactions were assessed separately, while the remainder were classified according to the influence of each reaction on the investigation and the need for treatment. From the results and a review of the literature we conclude that when there is a clear clinical indication for excretion urography a dose of contrast medium containing up to 600 mg iodine/kg body weight should be injected rapidly. Prophylactic antihistamine treatment and pretesting should be abandoned. Special care is needed for small infants and the lederly and for patients with renal or hepatic failure, myeloma, heart disease, or a history of previous major reaction. Full resuscitation facilities must always be available.", "contents": "Acute reactions to urographic contrast media. A prospective study of 3509 consecutive patients examined by excretion urography has been conducted to assess the incidence and significance of the untoward effects of urographic contrast media. Four compounds were used in doses containing 160 to 500 mg iodine/kg body weight. Toxic effects, arm pain, and allegic reactions were assessed separately, while the remainder were classified according to the influence of each reaction on the investigation and the need for treatment. From the results and a review of the literature we conclude that when there is a clear clinical indication for excretion urography a dose of contrast medium containing up to 600 mg iodine/kg body weight should be injected rapidly. Prophylactic antihistamine treatment and pretesting should be abandoned. Special care is needed for small infants and the lederly and for patients with renal or hepatic failure, myeloma, heart disease, or a history of previous major reaction. Full resuscitation facilities must always be available."}
{"id": "PMID:236066", "title": "Pulmonary function in asthmatic patients in remission.", "content": "Thirty-five asthmatic patients (average age 28 years) who attended a pulmonary function laboratory when their mean ratio of forced expiratory volume in one second: forced vital capacity was 81 per cent (within the normal range for their age group) had arterial hypoxaemia and hypocapnia. These were probably secondary to lung hyperinflation and pulmonary ventilation/perfusion imbalance. The pulmonary abnormalities of bronchial asthma are not always detected by simple spirometric tests and the results of such tests should be interpreted cautiously.", "contents": "Pulmonary function in asthmatic patients in remission. Thirty-five asthmatic patients (average age 28 years) who attended a pulmonary function laboratory when their mean ratio of forced expiratory volume in one second: forced vital capacity was 81 per cent (within the normal range for their age group) had arterial hypoxaemia and hypocapnia. These were probably secondary to lung hyperinflation and pulmonary ventilation/perfusion imbalance. The pulmonary abnormalities of bronchial asthma are not always detected by simple spirometric tests and the results of such tests should be interpreted cautiously."}
{"id": "PMID:236067", "title": "Changes in haemoglobin binding curve and oxygen transport in chronic hypoxic lung disease.", "content": "Direct measurements of the factors determining blood oxygen transport in 10 patients with chronic hypoxic respiratory failure led to the conclusion that wide differences in the position of their oxygen binding curves, due to spontaneous differences in red-cell 2, 3-diphosphoglycerate, had little effect on oxygen delivery to the tissues, as assessed by the mixed venous oxygen tension when they were breathing air. This result arises from the shape of the oxygen binding curve. A drug which could shift the curve to the right would help tissue oxygenation in cardiogenic and other forms of shock, when a low cardiac output can not be improved though arterial blood can be well oxygenated.", "contents": "Changes in haemoglobin binding curve and oxygen transport in chronic hypoxic lung disease. Direct measurements of the factors determining blood oxygen transport in 10 patients with chronic hypoxic respiratory failure led to the conclusion that wide differences in the position of their oxygen binding curves, due to spontaneous differences in red-cell 2, 3-diphosphoglycerate, had little effect on oxygen delivery to the tissues, as assessed by the mixed venous oxygen tension when they were breathing air. This result arises from the shape of the oxygen binding curve. A drug which could shift the curve to the right would help tissue oxygenation in cardiogenic and other forms of shock, when a low cardiac output can not be improved though arterial blood can be well oxygenated."}
{"id": "PMID:236073", "title": "Functional and biochemical aspects of catecholamine metabolism in brain under hypoxia.", "content": "Animals exposed to 6% oxygen showed a partial inhibition of the rate of tyrosine hydroxylation and a blockade of the conditioned avoidance response. The behavioral disruption was suggested to result, at least in part, from a dopaminergic disturbance, since the behavior was restored by the administration of DOPA or apomorphine but not by 5-hydroxytryptophan. Biochemical data showed a selective retardation in brain dopamine (DA) disappearance after synthesis inhibition. Methoxytyramine formation was markedly retarded. Analysis of this effect indicated that the decreased DA turnover was related to the release of transmitter rather than to an effect on catechol-O-methyltransferase (COMT) or monoamine oxidase (MAO). In addition, there was evidence for a partial inhibition of MAO activity by hypoxia as well as a decreased activity of dopamine-betahydroxylase. It was concluded that the disruption of behavior was related to decreased dopaminergic receptor activation and that decreased synthesis played at most a contributory role.", "contents": "Functional and biochemical aspects of catecholamine metabolism in brain under hypoxia. Animals exposed to 6% oxygen showed a partial inhibition of the rate of tyrosine hydroxylation and a blockade of the conditioned avoidance response. The behavioral disruption was suggested to result, at least in part, from a dopaminergic disturbance, since the behavior was restored by the administration of DOPA or apomorphine but not by 5-hydroxytryptophan. Biochemical data showed a selective retardation in brain dopamine (DA) disappearance after synthesis inhibition. Methoxytyramine formation was markedly retarded. Analysis of this effect indicated that the decreased DA turnover was related to the release of transmitter rather than to an effect on catechol-O-methyltransferase (COMT) or monoamine oxidase (MAO). In addition, there was evidence for a partial inhibition of MAO activity by hypoxia as well as a decreased activity of dopamine-betahydroxylase. It was concluded that the disruption of behavior was related to decreased dopaminergic receptor activation and that decreased synthesis played at most a contributory role."}
{"id": "PMID:236076", "title": "The effect of pH and blood gas correction in DPG and plasma potassium content of stored blood.", "content": "During storage of CPD preserved blood, red cell DPG decreases and plasma potassium increases, the changes becoming more marked with increasing duration of storage. Correction of the blood gas and pH alterations of stored blood decreases plasma potassium and increases red cell DPG, but they do not return to normal except in blood stored less than seven days. There is a highly significant correlation between increasing red cell DPG and decreasing plasma potassium as the pH and blood gases of stored blood are restored to physiological range.", "contents": "The effect of pH and blood gas correction in DPG and plasma potassium content of stored blood. During storage of CPD preserved blood, red cell DPG decreases and plasma potassium increases, the changes becoming more marked with increasing duration of storage. Correction of the blood gas and pH alterations of stored blood decreases plasma potassium and increases red cell DPG, but they do not return to normal except in blood stored less than seven days. There is a highly significant correlation between increasing red cell DPG and decreasing plasma potassium as the pH and blood gases of stored blood are restored to physiological range."}
{"id": "PMID:236077", "title": "Evidence for NAD nucleosidase in rabbit-liver lysosomes.", "content": "A method is described for the isolation of secondary lysosomes from homogenates of rabbit liver; The uptake of Triton WR-1339 by rabbit-liver lysosomes when administered by intraperitoneal injection was used to decrease the density of secondary lysosomes. Lysosomal fractions prepared by this method contain an NAD nucleosidase (NAD glycohydrolase, EC 3;2.25), an enzyme which has previously been considered to be associated with other subcellular fractions. The enzyme has maximum activity at pH 6 and cleaves both NAD and NADP. It is inhibited by nicotinamide (Ki equals 4.5 mM) and by HgCl2. Both nucleosidase and 2'-nucleotidase show in-vitro latency typical of lysosomal acid hydrolases. Rabbit-liver plasma-membrane fractions were isolated which contained most 5'-nucleotidase but relatively little nucleosidase, whereas rabbit liver lysosomes contain both 5'-nucleotidase and nucleosidase enzymes but little adenyl cyclase.", "contents": "Evidence for NAD nucleosidase in rabbit-liver lysosomes. A method is described for the isolation of secondary lysosomes from homogenates of rabbit liver; The uptake of Triton WR-1339 by rabbit-liver lysosomes when administered by intraperitoneal injection was used to decrease the density of secondary lysosomes. Lysosomal fractions prepared by this method contain an NAD nucleosidase (NAD glycohydrolase, EC 3;2.25), an enzyme which has previously been considered to be associated with other subcellular fractions. The enzyme has maximum activity at pH 6 and cleaves both NAD and NADP. It is inhibited by nicotinamide (Ki equals 4.5 mM) and by HgCl2. Both nucleosidase and 2'-nucleotidase show in-vitro latency typical of lysosomal acid hydrolases. Rabbit-liver plasma-membrane fractions were isolated which contained most 5'-nucleotidase but relatively little nucleosidase, whereas rabbit liver lysosomes contain both 5'-nucleotidase and nucleosidase enzymes but little adenyl cyclase."}
{"id": "PMID:236078", "title": "Structural studies of staphylococcal protease. I. Spin labelling of the active site and a comparison with other proteases.", "content": "Staphylococcus aureus protease has been spin-labelled at the active-site serine residue with the monocyclic-phosphorus spin label (MSL), 1-oxyl-2,2,6,6-tetramethyl-4-peperi-dinylethylphosphorofluoridate. The electron paramagnetic resonance (E.P.R.) sbectra of the protease in different buffers at various pH's have been analyzed and compared with those of trypsin, subtilisin BPN', and alpha-chymotrypsin under identical conditions. In a given buffer, the shape of E.P.R. signals of spin-labelled staphylococcal protease is unaffected by pH changes except below pH 4.0, at which a gradual loss of conformational integrity of the active site occurs. In bicarbonate buffer and particularly in acetate buffer, the mobility of the label is much more restricted than in phosphate buffer or in potassium chloride solution. The implications of this finding are discussed in terms of a model whereby the label is able to orient towards two different but adjacent regions of the active site. The relative population of the label in each of these orientations is believed to be buffer-dependent. An attempt to correlate the shape of the te.p.r. signals with the pH values of maximal proteolytic avtivity of the enzyme is also presented. These results show that to obtain meaningful information from a comparative spin label study of the geometry of the active site of serine proteases, particular care should be exercised to assure that the different proteases experience identical conditions of pH, buffer, and temperature.", "contents": "Structural studies of staphylococcal protease. I. Spin labelling of the active site and a comparison with other proteases. Staphylococcus aureus protease has been spin-labelled at the active-site serine residue with the monocyclic-phosphorus spin label (MSL), 1-oxyl-2,2,6,6-tetramethyl-4-peperi-dinylethylphosphorofluoridate. The electron paramagnetic resonance (E.P.R.) sbectra of the protease in different buffers at various pH's have been analyzed and compared with those of trypsin, subtilisin BPN', and alpha-chymotrypsin under identical conditions. In a given buffer, the shape of E.P.R. signals of spin-labelled staphylococcal protease is unaffected by pH changes except below pH 4.0, at which a gradual loss of conformational integrity of the active site occurs. In bicarbonate buffer and particularly in acetate buffer, the mobility of the label is much more restricted than in phosphate buffer or in potassium chloride solution. The implications of this finding are discussed in terms of a model whereby the label is able to orient towards two different but adjacent regions of the active site. The relative population of the label in each of these orientations is believed to be buffer-dependent. An attempt to correlate the shape of the te.p.r. signals with the pH values of maximal proteolytic avtivity of the enzyme is also presented. These results show that to obtain meaningful information from a comparative spin label study of the geometry of the active site of serine proteases, particular care should be exercised to assure that the different proteases experience identical conditions of pH, buffer, and temperature."}
{"id": "PMID:236079", "title": "Rabbit cardiac myosin. II. Proteolytic fragmentation with insolubilized papain.", "content": "The substructure of the cardiac myosin molecule was examined by the limited proteolytic digestion of the parent molecule with (dialdehyde starch)-methylenedianiline-mercuripapain, S-MDA-mercuripapain, at low temperatures and neutral pH, using moderate enzyme to myosin rations. Pertinent properties of the insoluble enzyme complex were also examined. Kinetic, ultracentrifugal, and chromatographic observations of the fragmentation process revealed that a single type of lytic reaction occurs during the early stages, predominately releasing heavy meromyosin subfragment 1 (HMM-S1) and myosin rods. With further time digestion, the rods are additionally cleaved yielding light meromyosin and HMM-S2, and HMM-S1 is found to be partially degraded. The major proteolytic subfragments were isolated, purified, and characterized with respect to their enzymatic, optical, amino acid, and physicochemical properties. Only HMM-S1 exhibited Ca-2+-activated ATPase activity, and at a level three- to fourfold higher than that of native myosin. Moreover, its hydrohynamic properties suggest that it is globular in structure. On the other hand, light meromyosin-A (LMM-A) (which consists mainly of rods), and HMM-S2 appear to be highly asymmetric, rigid, alpha-helical molecules devoid of the amino acid proline. Strong similarities were evident in all aspects upon comparison of these results with documented information concerning the skeletal system. On the basis of the physical and chemical properties of the proteolytic subfragments relative to that of native myosin, it was further concluded that the cardiac myosin molecule is a double-stranded, alpha-helical rod ending in tow subfragment 1 globules, of which only one may be enzymatically active at a time.", "contents": "Rabbit cardiac myosin. II. Proteolytic fragmentation with insolubilized papain. The substructure of the cardiac myosin molecule was examined by the limited proteolytic digestion of the parent molecule with (dialdehyde starch)-methylenedianiline-mercuripapain, S-MDA-mercuripapain, at low temperatures and neutral pH, using moderate enzyme to myosin rations. Pertinent properties of the insoluble enzyme complex were also examined. Kinetic, ultracentrifugal, and chromatographic observations of the fragmentation process revealed that a single type of lytic reaction occurs during the early stages, predominately releasing heavy meromyosin subfragment 1 (HMM-S1) and myosin rods. With further time digestion, the rods are additionally cleaved yielding light meromyosin and HMM-S2, and HMM-S1 is found to be partially degraded. The major proteolytic subfragments were isolated, purified, and characterized with respect to their enzymatic, optical, amino acid, and physicochemical properties. Only HMM-S1 exhibited Ca-2+-activated ATPase activity, and at a level three- to fourfold higher than that of native myosin. Moreover, its hydrohynamic properties suggest that it is globular in structure. On the other hand, light meromyosin-A (LMM-A) (which consists mainly of rods), and HMM-S2 appear to be highly asymmetric, rigid, alpha-helical molecules devoid of the amino acid proline. Strong similarities were evident in all aspects upon comparison of these results with documented information concerning the skeletal system. On the basis of the physical and chemical properties of the proteolytic subfragments relative to that of native myosin, it was further concluded that the cardiac myosin molecule is a double-stranded, alpha-helical rod ending in tow subfragment 1 globules, of which only one may be enzymatically active at a time."}
{"id": "PMID:236080", "title": "Protein kinases in rat testes: evidence for different fractions of the enzyme.", "content": "Protein kinase activity of rat testis homogenate was separated into five fractions by means of pH 4.8 acidification and DEAE-cellulose chromatography. The five fractions showed a peculiar pattern of activity and cAMP dependency with the substrates used: casein, protamine, histone mixture, arginine-rich histone, lysine-rich histone, and phosvitin. The casein-sepharose substrate affinity column separated two fractions from the pH 4.8 precipitate. Peak number one phosphorylates histone preferently and is cAMP-dependent, while peak number tow has a strong affinity toward casein as substrate and is non cAMP-dependent.", "contents": "Protein kinases in rat testes: evidence for different fractions of the enzyme. Protein kinase activity of rat testis homogenate was separated into five fractions by means of pH 4.8 acidification and DEAE-cellulose chromatography. The five fractions showed a peculiar pattern of activity and cAMP dependency with the substrates used: casein, protamine, histone mixture, arginine-rich histone, lysine-rich histone, and phosvitin. The casein-sepharose substrate affinity column separated two fractions from the pH 4.8 precipitate. Peak number one phosphorylates histone preferently and is cAMP-dependent, while peak number tow has a strong affinity toward casein as substrate and is non cAMP-dependent."}
{"id": "PMID:236081", "title": "The control of pyruvate kinases of Escherichia coli. II. Effectors and regulatory properties of the enzyme activated by ribose 5-phosphate.", "content": "The pyruvate kinases of Escherichia coli activated by ribose 5-phosphate (RP) has been partially purified. The active form of the enzyme has a molecular weight of about 180 000 as judged by sucrose density gradient centrifugations and Sephadex G-150 chromatography. On dissociation in the absence of sulfhydryl reagents such as dithiothreitol, the enzyme is inactivated and it has a molecular weight of about 110 000. Various substrates and effectors of the enzyme, with the exception of phosphate, do not influence the association-dissociation equilibrium of the enzyme. The enzyme, unlike pyruvate kinases from many other sources, is not activated by potassium ions. Sulfate and phosphate ions are inhibitory to the enzyme. Phosphate seems to be an allosteric inhibitor and its effect is completely antagonized by activators. The enzyme is activated in an allosteric manner by two classes of compounds, nucleoside monophosphates and sugar phosphates of the hexose monophosphate pathway. Amongst the nucleotides, guanosine 5'-phosphate and adenosine 5'-phosphate are the most effective activators. Amongst the hexose monophosphate pathway intermediates, RP is the most powerful activator, with apparent activation constants as low as 1 Mu. Sugar phosphates esterified at C-1 or both terminal positions are entirely ineffective in activation. The effectors act by changing the Michaelis constant for the substrates. Both of the substrates of the enzyme, adenosine diphosphate and phosphoenolpyruvate, yield cooperative-concentration plots in the presence of unsaturating concentrations of the fixed changing substrate. The initial velocity plots for both substrates become hyperbolic in the presence of saturating concentrations of RP.", "contents": "The control of pyruvate kinases of Escherichia coli. II. Effectors and regulatory properties of the enzyme activated by ribose 5-phosphate. The pyruvate kinases of Escherichia coli activated by ribose 5-phosphate (RP) has been partially purified. The active form of the enzyme has a molecular weight of about 180 000 as judged by sucrose density gradient centrifugations and Sephadex G-150 chromatography. On dissociation in the absence of sulfhydryl reagents such as dithiothreitol, the enzyme is inactivated and it has a molecular weight of about 110 000. Various substrates and effectors of the enzyme, with the exception of phosphate, do not influence the association-dissociation equilibrium of the enzyme. The enzyme, unlike pyruvate kinases from many other sources, is not activated by potassium ions. Sulfate and phosphate ions are inhibitory to the enzyme. Phosphate seems to be an allosteric inhibitor and its effect is completely antagonized by activators. The enzyme is activated in an allosteric manner by two classes of compounds, nucleoside monophosphates and sugar phosphates of the hexose monophosphate pathway. Amongst the nucleotides, guanosine 5'-phosphate and adenosine 5'-phosphate are the most effective activators. Amongst the hexose monophosphate pathway intermediates, RP is the most powerful activator, with apparent activation constants as low as 1 Mu. Sugar phosphates esterified at C-1 or both terminal positions are entirely ineffective in activation. The effectors act by changing the Michaelis constant for the substrates. Both of the substrates of the enzyme, adenosine diphosphate and phosphoenolpyruvate, yield cooperative-concentration plots in the presence of unsaturating concentrations of the fixed changing substrate. The initial velocity plots for both substrates become hyperbolic in the presence of saturating concentrations of RP."}
{"id": "PMID:236082", "title": "Survey of antibiotic residues in Canadian slaughter animals.", "content": "Kidneys and urine of cattle, swine, sheep and chickens were tested for bacterial growth inhibitors using Bacillus subtilis and Sarcina lutea as test organisms. Results were as follows: 211 beef kidneys four positive, 611 swine kidneys five positive, 27 sheep and 120 chicken kidneys all negative, 2108 beef urine 76 positive, 2409 swine urine 186 positive, 176 sheep urine 17 positive. Strongest reactions were obtained with B. subtilis on phosphate buffered pH 6.0 plates. Larger zones were produced by urine from injected animals than by tissue samples.", "contents": "Survey of antibiotic residues in Canadian slaughter animals. Kidneys and urine of cattle, swine, sheep and chickens were tested for bacterial growth inhibitors using Bacillus subtilis and Sarcina lutea as test organisms. Results were as follows: 211 beef kidneys four positive, 611 swine kidneys five positive, 27 sheep and 120 chicken kidneys all negative, 2108 beef urine 76 positive, 2409 swine urine 186 positive, 176 sheep urine 17 positive. Strongest reactions were obtained with B. subtilis on phosphate buffered pH 6.0 plates. Larger zones were produced by urine from injected animals than by tissue samples."}
{"id": "PMID:236083", "title": "The use of a travelling ophthalmic technologist in a remote, sparsely populated region.", "content": "An attempt has been made to meet the ophthalmological needs of the population of the 500,000 square mile Mackenzie Zone of the Canadian Northwest Territories by the use of a well trained ophtalmic technologist who travels to each of the small, widely separated communities. He carries out the necessary refractions and screens patients selected by the local nurses for ocular disease and/or motility problems for referral to the ophtalmologist in charge. Patients requiring treatment or further investigation are referred to the supervising ophtalmologist who will provide instructions by phone or radio, will see them on a subsequent visit, or if indicated, will have them evacuated to the well equipped treatment centre in Yellowknife. Some of the advantages of this programme are as follows: 1. Communities are visited on a regular schedule with reasonable frequency by the same personnel. 2. The skills and training of the ophthalmologist are more effectively used by enabling him to spend most of his time at the centre where adequate medical and surgical facilities are available. 3. Standardized, centralized records are kept which are identical to those in patient's home community. It is suggested that the use of well-trained paramedical personnel may be of significant value in the provision of adequate medical care to widely dispersed population groups in the far north.", "contents": "The use of a travelling ophthalmic technologist in a remote, sparsely populated region. An attempt has been made to meet the ophthalmological needs of the population of the 500,000 square mile Mackenzie Zone of the Canadian Northwest Territories by the use of a well trained ophtalmic technologist who travels to each of the small, widely separated communities. He carries out the necessary refractions and screens patients selected by the local nurses for ocular disease and/or motility problems for referral to the ophtalmologist in charge. Patients requiring treatment or further investigation are referred to the supervising ophtalmologist who will provide instructions by phone or radio, will see them on a subsequent visit, or if indicated, will have them evacuated to the well equipped treatment centre in Yellowknife. Some of the advantages of this programme are as follows: 1. Communities are visited on a regular schedule with reasonable frequency by the same personnel. 2. The skills and training of the ophthalmologist are more effectively used by enabling him to spend most of his time at the centre where adequate medical and surgical facilities are available. 3. Standardized, centralized records are kept which are identical to those in patient's home community. It is suggested that the use of well-trained paramedical personnel may be of significant value in the provision of adequate medical care to widely dispersed population groups in the far north."}
{"id": "PMID:236084", "title": "Cellular immunity to xenogeneic corneal grafts in rabbits.", "content": "We wished to determine whether a small orthotopic corneal xenograft could sensitize a host systemically. Ten rabbits were grafted with interlamellar bovine cornea and pre- and postoperative blood samples tested by the H3 thymidine incorporation test (micro-method). The leucocyte migration inhibition test was applied in 3 animals. A skin test was performed on all rabbits in the 4th postoperative week. The challenging antigen used  was a homogenate of pooled bovine corneas. Clinically and histologically each rabbit showed a characteristic corneal graft reaction. Where performed, leucocyte migration inhibition tests were positive after grafting as were all skin tests. The H3 thymidine incorporation test did not detect specific systemic sensitization although increased numbers of DNA synthesizing cells were present in the blood during the graft reaction. We conclude that a bovine corneal xenograft can induce systemic sensitization in a rabbit host.", "contents": "Cellular immunity to xenogeneic corneal grafts in rabbits. We wished to determine whether a small orthotopic corneal xenograft could sensitize a host systemically. Ten rabbits were grafted with interlamellar bovine cornea and pre- and postoperative blood samples tested by the H3 thymidine incorporation test (micro-method). The leucocyte migration inhibition test was applied in 3 animals. A skin test was performed on all rabbits in the 4th postoperative week. The challenging antigen used  was a homogenate of pooled bovine corneas. Clinically and histologically each rabbit showed a characteristic corneal graft reaction. Where performed, leucocyte migration inhibition tests were positive after grafting as were all skin tests. The H3 thymidine incorporation test did not detect specific systemic sensitization although increased numbers of DNA synthesizing cells were present in the blood during the graft reaction. We conclude that a bovine corneal xenograft can induce systemic sensitization in a rabbit host."}
{"id": "PMID:236085", "title": "Degradation of feather keratin by culture filtrates of Streptomyces fradiae.", "content": "Treatment of milled defatted capon feathers with filtrates of Steptomyces fradiae ATCC 10745 that had been concentrated 20 times showed that the most keratin degradation in 0.5h occurred at pH 8.0 and 60degrees C. If assay time was extended, however, adecrease in reaction rate occurred and appeared to result from keratinase instability at elevated temperatures. Exposure of commercial feather meal to unconcentrated culturefiltrates for 15 h produced greatest degradation at 50 degrees C.", "contents": "Degradation of feather keratin by culture filtrates of Streptomyces fradiae. Treatment of milled defatted capon feathers with filtrates of Steptomyces fradiae ATCC 10745 that had been concentrated 20 times showed that the most keratin degradation in 0.5h occurred at pH 8.0 and 60degrees C. If assay time was extended, however, adecrease in reaction rate occurred and appeared to result from keratinase instability at elevated temperatures. Exposure of commercial feather meal to unconcentrated culturefiltrates for 15 h produced greatest degradation at 50 degrees C."}
{"id": "PMID:236086", "title": "Differential isolatoion of Pythium species from soil by means of selective media,temperature, and pH.", "content": "Pythium aphanidermatum, with an optimum temperature for growth at 35C, grew welland was readily isolated from soil on pimaricin-vancomycin medium (MPVM) when incubated for 24h at 38-40C. The pH of the medium affected recovery; maximum numbers developed above pH 6.0. Other Pythium spp. were recovered on MPVM at 20-25C, but were excluded by incubation at 38-40C. These Pythium spp. included P. ultimun, P. paroecandrum, P. irregular, P. mamillatum, and an unidentified Pythium sp. These species grew well and were readily siolated from soil on gallic acid medium (GAM) when incubated for 24-8h at 20 C.P. aphanidermatum and P. myriotylum grew from mycelium on GAM, but their oospores did not germinate nor could they be isolated from soilon this medium. P. myriotylum grew well on MPVM, but was only rarely isolated, evenfrom soils with known high potential for disease caused by P. myriotylum. Propagules of Pythium were enumerated by a plate-dilution frequency method or by a smearplateethod is valuable for studies on the ecology, survival, and inoculum potential in soils with mixed populations of P. aphanidermatum and other Pythium spp.", "contents": "Differential isolatoion of Pythium species from soil by means of selective media,temperature, and pH. Pythium aphanidermatum, with an optimum temperature for growth at 35C, grew welland was readily isolated from soil on pimaricin-vancomycin medium (MPVM) when incubated for 24h at 38-40C. The pH of the medium affected recovery; maximum numbers developed above pH 6.0. Other Pythium spp. were recovered on MPVM at 20-25C, but were excluded by incubation at 38-40C. These Pythium spp. included P. ultimun, P. paroecandrum, P. irregular, P. mamillatum, and an unidentified Pythium sp. These species grew well and were readily siolated from soil on gallic acid medium (GAM) when incubated for 24-8h at 20 C.P. aphanidermatum and P. myriotylum grew from mycelium on GAM, but their oospores did not germinate nor could they be isolated from soilon this medium. P. myriotylum grew well on MPVM, but was only rarely isolated, evenfrom soils with known high potential for disease caused by P. myriotylum. Propagules of Pythium were enumerated by a plate-dilution frequency method or by a smearplateethod is valuable for studies on the ecology, survival, and inoculum potential in soils with mixed populations of P. aphanidermatum and other Pythium spp."}
{"id": "PMID:236087", "title": "N-6-(delta-2-isopentenyl) adenosine: hydrolysis by a mucleosidase isolated from Lactobacillus acidophilus cells.", "content": "A nucleosidase activity has been isolated from Lactobacillus acidophilus which rapidly hydrolyses N-6 (delta-2-isopentenyl) adenosine to its corresponding base, N-6(delta-2-isopentenyl) adenine. The activity can be distinguished from the spleen exzyme (EC. 2.4.2.1), a purine nucleoside transferase, on the basis of its substrate specificity, electrophoretic behavior, and nondependence on phosphate. The bacterial enzyme hydrolyzes both inosine and isopentenyl adenosine, giving Km values of 63.3muM and 177 muM respectively. The presence of this enzyme in bacteria counts for the rapid conversion of the parent nucleoside to isopentenyl adenine, which has been observed in these cells. The enzyme thus assumes importance as one of the catabolic activities available to the cell for metabolizing the cytokinin, N-6-(delta-2-isopentenyl) adenosine.", "contents": "N-6-(delta-2-isopentenyl) adenosine: hydrolysis by a mucleosidase isolated from Lactobacillus acidophilus cells. A nucleosidase activity has been isolated from Lactobacillus acidophilus which rapidly hydrolyses N-6 (delta-2-isopentenyl) adenosine to its corresponding base, N-6(delta-2-isopentenyl) adenine. The activity can be distinguished from the spleen exzyme (EC. 2.4.2.1), a purine nucleoside transferase, on the basis of its substrate specificity, electrophoretic behavior, and nondependence on phosphate. The bacterial enzyme hydrolyzes both inosine and isopentenyl adenosine, giving Km values of 63.3muM and 177 muM respectively. The presence of this enzyme in bacteria counts for the rapid conversion of the parent nucleoside to isopentenyl adenine, which has been observed in these cells. The enzyme thus assumes importance as one of the catabolic activities available to the cell for metabolizing the cytokinin, N-6-(delta-2-isopentenyl) adenosine."}
{"id": "PMID:236088", "title": "Laboratory diagnosis and monitoring of rheumatologic diseases.", "content": "Improved laboratory investigative techniques now foster an increased clinical interest in and awareness of the rheumatologic disease. This review is a discussion of the relevance of laboratory tests used in the more common rheumatologic disorders and of their role in both the diagnosis and assessment of these diseases from the standpoint of the practising clinician.", "contents": "Laboratory diagnosis and monitoring of rheumatologic diseases. Improved laboratory investigative techniques now foster an increased clinical interest in and awareness of the rheumatologic disease. This review is a discussion of the relevance of laboratory tests used in the more common rheumatologic disorders and of their role in both the diagnosis and assessment of these diseases from the standpoint of the practising clinician."}
{"id": "PMID:236090", "title": "Quantitative precipitin studies on the specificity of an extract from Tridacna maxima (R\u00f6ding).", "content": "Haemolymph from the clam Tridacna maxima precipitated with purified H-blood-group substances, Helix pomatia galactogen, and pneumococcus type XIV polysaccharide. Although gel diffusion, gel electrophoresis, and inhibition experiments indicated that only a single precipitating lectin was present in the haemolymph, quantitative precipitin and haemagglutination results suggested that a second agglutinin with anti-H-like specificity was also present. Evidence obtained from hapten inhibition experiments indicated that the precipitin that reacts with pneumococcus type XIV polysaccharide can be inhibited by a number of simple sugars. Of the compounds tested, 2-acetamido-2-deoxy-D-galactose was the best inhibitor of precipitation with pneumococcus type XIV polysaccharide and of haemagglutination with human erythrocytes, but the inhibition experiments showed that the extract was also markedly inhibited by D-galactosamine hydrochloride, D-galactose, lactose, and p-nitrophenyl beta-D-galactopyranoside. The latter compound was more active than its parent sugar, which was in turn a more potent inhibitor than p-nitrophenyl alpha-D-galactopyranoside. Melibiose, raffinose, and stachyose, compounds which each contain terminal alpha-linked D-galactopyranosyl residues, were relatively weak inhibitors. The combining sites of the lectin that reacts with pneumococcus type XIV polysaccharide appear, therefore, to be most complementary to 2-acetamido-2-deoxy-D-galactopyranosyl residues, probably in beta linkage.", "contents": "Quantitative precipitin studies on the specificity of an extract from Tridacna maxima (R\u00f6ding). Haemolymph from the clam Tridacna maxima precipitated with purified H-blood-group substances, Helix pomatia galactogen, and pneumococcus type XIV polysaccharide. Although gel diffusion, gel electrophoresis, and inhibition experiments indicated that only a single precipitating lectin was present in the haemolymph, quantitative precipitin and haemagglutination results suggested that a second agglutinin with anti-H-like specificity was also present. Evidence obtained from hapten inhibition experiments indicated that the precipitin that reacts with pneumococcus type XIV polysaccharide can be inhibited by a number of simple sugars. Of the compounds tested, 2-acetamido-2-deoxy-D-galactose was the best inhibitor of precipitation with pneumococcus type XIV polysaccharide and of haemagglutination with human erythrocytes, but the inhibition experiments showed that the extract was also markedly inhibited by D-galactosamine hydrochloride, D-galactose, lactose, and p-nitrophenyl beta-D-galactopyranoside. The latter compound was more active than its parent sugar, which was in turn a more potent inhibitor than p-nitrophenyl alpha-D-galactopyranoside. Melibiose, raffinose, and stachyose, compounds which each contain terminal alpha-linked D-galactopyranosyl residues, were relatively weak inhibitors. The combining sites of the lectin that reacts with pneumococcus type XIV polysaccharide appear, therefore, to be most complementary to 2-acetamido-2-deoxy-D-galactopyranosyl residues, probably in beta linkage."}
{"id": "PMID:236091", "title": "Molecular immunological heterogeneity of the Salmonella zuerich [1, 9, 12, (46), 27] cell-wall polysaccharides.", "content": "Extraction of O specific polysaccharide from S. zuerich leads to three fractions (ZA, ZB, ZC). Polysaccharide ZB carries specificities 1, 27, and 46, present on the Salmonella cells. It exhibits a factor 27 that is very similar to that present on the S. typhi T2 1-minus 27-+ polysaccharide, a factor 1 that is close to that present on S. senftenberg polysaccharide, and a factor 46 that gives a very weak cross-reaction with anti-46 antibodies. Polysaccharides ZA and ZB are immunologically different and ZB contains two distinct fractions: ZB 1-minus devoid of Ofactor 1 and carrying the specificities 46 and 27 mostly, of not completely, on the same molecule (46, 27); and ZB1-+ carrying O factors 1, (46), 27. ZB 1-+ is composed of at least two different molecules: [1,(46)] precipitable with anti-1 antibodies but only coprecipitable with anti-46 antibodies; and (1, 27) precipitable with both anti-1 and anti-27 antibodies. Molecules [1, (46)] precipitate only part of the anti-1 antibodies precipitable by (1, 27). The smaller precipitation of anti-27 antibodies (when factor 27 is present together with factor 1 on the same molecule) and the coprecipitation, instead of precipitation, of anti-46 antibodies (when factors 46 and 1 are present on the same molecule) may be explained by a sterical hindrance between O-factors 1 and 27, and 1 and 46. The molecular, immunological heterogeneity of the polysaccharides extracted from S. zuerich would result from the presence on the cells of two kinds of O polysaccharides: one with, the other without O factor1, which is related to the presence of a side-chain of an alpha-D-glucosyl residue. A structure for S. zuerich polysaccharide is proposed.", "contents": "Molecular immunological heterogeneity of the Salmonella zuerich [1, 9, 12, (46), 27] cell-wall polysaccharides. Extraction of O specific polysaccharide from S. zuerich leads to three fractions (ZA, ZB, ZC). Polysaccharide ZB carries specificities 1, 27, and 46, present on the Salmonella cells. It exhibits a factor 27 that is very similar to that present on the S. typhi T2 1-minus 27-+ polysaccharide, a factor 1 that is close to that present on S. senftenberg polysaccharide, and a factor 46 that gives a very weak cross-reaction with anti-46 antibodies. Polysaccharides ZA and ZB are immunologically different and ZB contains two distinct fractions: ZB 1-minus devoid of Ofactor 1 and carrying the specificities 46 and 27 mostly, of not completely, on the same molecule (46, 27); and ZB1-+ carrying O factors 1, (46), 27. ZB 1-+ is composed of at least two different molecules: [1,(46)] precipitable with anti-1 antibodies but only coprecipitable with anti-46 antibodies; and (1, 27) precipitable with both anti-1 and anti-27 antibodies. Molecules [1, (46)] precipitate only part of the anti-1 antibodies precipitable by (1, 27). The smaller precipitation of anti-27 antibodies (when factor 27 is present together with factor 1 on the same molecule) and the coprecipitation, instead of precipitation, of anti-46 antibodies (when factors 46 and 1 are present on the same molecule) may be explained by a sterical hindrance between O-factors 1 and 27, and 1 and 46. The molecular, immunological heterogeneity of the polysaccharides extracted from S. zuerich would result from the presence on the cells of two kinds of O polysaccharides: one with, the other without O factor1, which is related to the presence of a side-chain of an alpha-D-glucosyl residue. A structure for S. zuerich polysaccharide is proposed."}
{"id": "PMID:236092", "title": "The structure of capsular polysaccharide of the Pneumococcus type II.", "content": "The pneumococcus type II capsular polysaccharide (SII) is composed of singly-branched hexasaccharide repeating units, for which three alternative structures have been proposed. The correct structure has now been determined by consecutive eliminations of the sugar residues in the side chain. The terminal D-glucuronic acid group was eliminated by treating the fully methylated and esterified SIIpolysaccharide first with base, and then with weak acid. The hydroxyl group at C-6 in the penultimate D-glucose residue released by this elimination was transformed into the 6-deoxy-6-tosyl derivative, and the residue thereafter eliminated by treatment with base. As the side-chains were eliminated by these reactions, it is considered that they contain only two sugar residues, which thus excludes two of the three alternative structures. Structure 1 was further confirmed by subjecting SII to a Smith degradation, which yielded the tetrasaccharide L-Rhap-(1 yields 3)-L-Rhap-(1 yields 3)-L-Rhap-(1 yields 2-erythritol, characterised by methylation analysis.", "contents": "The structure of capsular polysaccharide of the Pneumococcus type II. The pneumococcus type II capsular polysaccharide (SII) is composed of singly-branched hexasaccharide repeating units, for which three alternative structures have been proposed. The correct structure has now been determined by consecutive eliminations of the sugar residues in the side chain. The terminal D-glucuronic acid group was eliminated by treating the fully methylated and esterified SIIpolysaccharide first with base, and then with weak acid. The hydroxyl group at C-6 in the penultimate D-glucose residue released by this elimination was transformed into the 6-deoxy-6-tosyl derivative, and the residue thereafter eliminated by treatment with base. As the side-chains were eliminated by these reactions, it is considered that they contain only two sugar residues, which thus excludes two of the three alternative structures. Structure 1 was further confirmed by subjecting SII to a Smith degradation, which yielded the tetrasaccharide L-Rhap-(1 yields 3)-L-Rhap-(1 yields 3)-L-Rhap-(1 yields 2-erythritol, characterised by methylation analysis."}
{"id": "PMID:236093", "title": "In situ studies on the effect of acid extraction on the DNA template activity of mature avian erythrocytes.", "content": "Exogenous E. coli RNA polymerase was used to determine the in situ DNA template activity of ethanol/acetone fixed avian erythrocytes. No RNA polymerase-catalyzed incorporation of 3H-UTP was detected in mature avian erythrocytes while simultaneously fixed avian lymphocytes did exhibit incorporation of 3H-UTP. Nuclei of mature erythrocytes which were subjected to treatments known to remove histones showed dramatic increases in RNA polymerase-catalyzed incorporation of 3H-UTP. The chromatin of treated cells was presumed to be more accessible to RNA polymerase as determined by the increase in RNA polymerase-catalyzed incorporation of 3H-UTP. Incubation of acid-treated nuclei in poly-L-lysine prior to incubation with RNA polymerase failed to inhibit the incorporation of 3H-UTP. Possible mechanisms for the inactivation of avian erythrocyte nuclei are discussed.", "contents": "In situ studies on the effect of acid extraction on the DNA template activity of mature avian erythrocytes. Exogenous E. coli RNA polymerase was used to determine the in situ DNA template activity of ethanol/acetone fixed avian erythrocytes. No RNA polymerase-catalyzed incorporation of 3H-UTP was detected in mature avian erythrocytes while simultaneously fixed avian lymphocytes did exhibit incorporation of 3H-UTP. Nuclei of mature erythrocytes which were subjected to treatments known to remove histones showed dramatic increases in RNA polymerase-catalyzed incorporation of 3H-UTP. The chromatin of treated cells was presumed to be more accessible to RNA polymerase as determined by the increase in RNA polymerase-catalyzed incorporation of 3H-UTP. Incubation of acid-treated nuclei in poly-L-lysine prior to incubation with RNA polymerase failed to inhibit the incorporation of 3H-UTP. Possible mechanisms for the inactivation of avian erythrocyte nuclei are discussed."}
{"id": "PMID:236096", "title": "The effect of plasma on the reaction of cyclophosphamide with 4(-p-nitrobenzyl)-pyridine.", "content": "Cyclophosphamide is not structurally modified by blood plasma and may be recovered quantitatively from it. The apparent loss of alkylating ability of cyclophosphamide, as measured by its ability to react with 4-(p-nitrobenzyl)-pyridine (NBP), following treatement with plasma is not, as has been reported, due to metabolism of the drug but rather to an inhibition of the colorimetric reaction by a constituent of the plasma. This inhibition is strongly pH dependent, reaching 100% when the pH of the solution of cyclophosphamide in plasma is above 8, and falling to less than 20% when the pH is below 6, but extraction with chloroform at pH 7 separates cyclophosphamide from the inhibitor. Although the nature of the inhibitor has not been elucidated, its presence in plasma is of great importance in the quantitative determination of cyclophosphamide, and may also be of significance in the biological effects of cyclophosphamide and other alkylating agents in vivo.", "contents": "The effect of plasma on the reaction of cyclophosphamide with 4(-p-nitrobenzyl)-pyridine. Cyclophosphamide is not structurally modified by blood plasma and may be recovered quantitatively from it. The apparent loss of alkylating ability of cyclophosphamide, as measured by its ability to react with 4-(p-nitrobenzyl)-pyridine (NBP), following treatement with plasma is not, as has been reported, due to metabolism of the drug but rather to an inhibition of the colorimetric reaction by a constituent of the plasma. This inhibition is strongly pH dependent, reaching 100% when the pH of the solution of cyclophosphamide in plasma is above 8, and falling to less than 20% when the pH is below 6, but extraction with chloroform at pH 7 separates cyclophosphamide from the inhibitor. Although the nature of the inhibitor has not been elucidated, its presence in plasma is of great importance in the quantitative determination of cyclophosphamide, and may also be of significance in the biological effects of cyclophosphamide and other alkylating agents in vivo."}
{"id": "PMID:236097", "title": "Infrared and Raman spectra of phosphatidyl-ethanolamine and related compounds.", "content": "Infrared and Raman spectra of phosphatidylethanolamine from Escherichia coli, L-alpha-glycero-phosphorylethanolamine and 0-phosphorylethanolamine were obtained. Most of the bands were assigned to each vibrational mode based on the N deuteration effect, comparison of the intensity in the infrared and Raman spectra and the depolarization degree measurement in the Raman spectra. The spectra of phosphatidylethanolamine can be interpreted by assuming that the molecule takes the dipolar ionic structure both in non-polar solvent and in solid.", "contents": "Infrared and Raman spectra of phosphatidyl-ethanolamine and related compounds. Infrared and Raman spectra of phosphatidylethanolamine from Escherichia coli, L-alpha-glycero-phosphorylethanolamine and 0-phosphorylethanolamine were obtained. Most of the bands were assigned to each vibrational mode based on the N deuteration effect, comparison of the intensity in the infrared and Raman spectra and the depolarization degree measurement in the Raman spectra. The spectra of phosphatidylethanolamine can be interpreted by assuming that the molecule takes the dipolar ionic structure both in non-polar solvent and in solid."}
{"id": "PMID:236098", "title": "A spectrophotometric scanning technique for the rapid determination of plasma hemoglobin.", "content": "1. A spectrophotometric scanning technique was used to quantitate hemoglobin concentrations in cardiac surgery patients and patients with other hemolytic disorders. 2. The fractional absorption of a portion of the 577 nm band of oxyhemoglobin was used in conjunction was used in conjunction with the absorption coefficient of oxyhemoglobin to relate absorption to plasma hemoblogin concentration. 3. The spectrophotometric scanning technique offers a rapid and accurate means of assessing plasma hemoglobin concentrations even in the presence of usual interferences by bilirubin, turbidity and methemalbumin.", "contents": "A spectrophotometric scanning technique for the rapid determination of plasma hemoglobin. 1. A spectrophotometric scanning technique was used to quantitate hemoglobin concentrations in cardiac surgery patients and patients with other hemolytic disorders. 2. The fractional absorption of a portion of the 577 nm band of oxyhemoglobin was used in conjunction was used in conjunction with the absorption coefficient of oxyhemoglobin to relate absorption to plasma hemoblogin concentration. 3. The spectrophotometric scanning technique offers a rapid and accurate means of assessing plasma hemoglobin concentrations even in the presence of usual interferences by bilirubin, turbidity and methemalbumin."}
{"id": "PMID:236099", "title": "Enzymatic study of GM-1 gangliosidosis.", "content": "Two types of GM-1 gangliosidosis were studied biochemically. Type 1 liver accumulated non-lipid hexosamine in addition to GM-1 ganglioside, but there was no increase of hexosamine and GM-1 in type 2 liver. The optimum pH of liver beta-galactosidase of type 1 and type 2 was 5--6 while that of the normal control was 4.5. Type 1 brain beta-galactosidase showed a slightly acidic optimum pH, i.e. 4.0 in comparison with that of the normal control. The optimum pH of type 2 brain beta-galactosidase was 5.5, like the liver enzyme. The thermostability of liver beta-galactosidase was the same in type 1 and type 2, while that of brain was different. Beta-galactosidase of type 1 and type 2 liver is more stable at 42 degrees C than the normal control, but a different thermostability was observed in type 1 and type 2 brain. Liver beta-galactosidase of type 1 showed one peak each at acid and neutral pH, and type 2 liver had only one peak at neutral pH.", "contents": "Enzymatic study of GM-1 gangliosidosis. Two types of GM-1 gangliosidosis were studied biochemically. Type 1 liver accumulated non-lipid hexosamine in addition to GM-1 ganglioside, but there was no increase of hexosamine and GM-1 in type 2 liver. The optimum pH of liver beta-galactosidase of type 1 and type 2 was 5--6 while that of the normal control was 4.5. Type 1 brain beta-galactosidase showed a slightly acidic optimum pH, i.e. 4.0 in comparison with that of the normal control. The optimum pH of type 2 brain beta-galactosidase was 5.5, like the liver enzyme. The thermostability of liver beta-galactosidase was the same in type 1 and type 2, while that of brain was different. Beta-galactosidase of type 1 and type 2 liver is more stable at 42 degrees C than the normal control, but a different thermostability was observed in type 1 and type 2 brain. Liver beta-galactosidase of type 1 showed one peak each at acid and neutral pH, and type 2 liver had only one peak at neutral pH."}
{"id": "PMID:236100", "title": "[Use of the measurement of gamma-glutamyltranspeptidase activity in serum to determine the success of cures for alcohol detoxification (author's transl)].", "content": "44 patients were studied during a 2-year period following a cure for alcohol detoxification. 29 patients (group A) did not start drinking again while 15 relapsed less than one year after their cure (group R). The average gamma GT activity (m) in mU per ml serum was, in group A, 148 (standard deviation, S.D. 184) at the beginning of the cure, 21 (S.D. 14) after one year and 19 (S.D. 13) after 2 years. During the same period there was no significant decrease in group R (cure: m 140, S.D. 161: 1 year: m 166, S.D. 164; 2 years: m 162, S.D. 163). On the other hand, all the subjects of group A who had a high gamma GT activity (greater than 29 mU/ml) at the start of the cure showed a decrease after one year.", "contents": "[Use of the measurement of gamma-glutamyltranspeptidase activity in serum to determine the success of cures for alcohol detoxification (author's transl)]. 44 patients were studied during a 2-year period following a cure for alcohol detoxification. 29 patients (group A) did not start drinking again while 15 relapsed less than one year after their cure (group R). The average gamma GT activity (m) in mU per ml serum was, in group A, 148 (standard deviation, S.D. 184) at the beginning of the cure, 21 (S.D. 14) after one year and 19 (S.D. 13) after 2 years. During the same period there was no significant decrease in group R (cure: m 140, S.D. 161: 1 year: m 166, S.D. 164; 2 years: m 162, S.D. 163). On the other hand, all the subjects of group A who had a high gamma GT activity (greater than 29 mU/ml) at the start of the cure showed a decrease after one year."}
{"id": "PMID:236101", "title": "Comparative investigations of some enzymatic parameters and liver scanning in the early detection of the malignant liver process.", "content": "In 30 patients with histologically verified malignant liver processes, the authors have examined the value of the serum activity of liver lactate dehydrogenase (LDH), alkaline phosphatase and gamma-glutamyltranspeptidase and in a number of patients, 5'-nucleotidase. These values were compared with the findings received from scintigraphy of the liver. Based on the results obtained, the authors have concluded that the activities of the gamma-glutamyltranspeptidase (gammaGT), 5'-nucleotidase and liver lactate dehydrogenase are more significantly increased in malignant processes of the liver than scintigraphy of the liver could register.", "contents": "Comparative investigations of some enzymatic parameters and liver scanning in the early detection of the malignant liver process. In 30 patients with histologically verified malignant liver processes, the authors have examined the value of the serum activity of liver lactate dehydrogenase (LDH), alkaline phosphatase and gamma-glutamyltranspeptidase and in a number of patients, 5'-nucleotidase. These values were compared with the findings received from scintigraphy of the liver. Based on the results obtained, the authors have concluded that the activities of the gamma-glutamyltranspeptidase (gammaGT), 5'-nucleotidase and liver lactate dehydrogenase are more significantly increased in malignant processes of the liver than scintigraphy of the liver could register."}
{"id": "PMID:236102", "title": "An automated technique for the analysis of plasma guanidino acids, and some findings in chronic renal disease.", "content": "A sensitive method for the quantitative determination of all guanidino compounds in human serum, including basic compounds such as methylguanidine, was developed by the adaptation of the Technicon automatic amino acid analyzer. Elution buffers with very high pH and molarity are employed for the elution of very basic compounds from the column. Automatic quantitative determination of the plasma guanidino compounds was performed with biacetyl alpha-naphthol, a specific reagent for the guanidino group. This method permitted the quantitative automatic determination of guanidino compounds in less than 1 ml of serum of normal or uremic patients. Guanidino propionic acid and guanidino succinic acid were identified in high concentrations in uremic sera. Methyl guanidine, and guanidine were in smaller concentrations. Guanidino acetic acid and guanidino butyric acid were present in normal plasma in quantities not significantly different from those in uremic plasma.", "contents": "An automated technique for the analysis of plasma guanidino acids, and some findings in chronic renal disease. A sensitive method for the quantitative determination of all guanidino compounds in human serum, including basic compounds such as methylguanidine, was developed by the adaptation of the Technicon automatic amino acid analyzer. Elution buffers with very high pH and molarity are employed for the elution of very basic compounds from the column. Automatic quantitative determination of the plasma guanidino compounds was performed with biacetyl alpha-naphthol, a specific reagent for the guanidino group. This method permitted the quantitative automatic determination of guanidino compounds in less than 1 ml of serum of normal or uremic patients. Guanidino propionic acid and guanidino succinic acid were identified in high concentrations in uremic sera. Methyl guanidine, and guanidine were in smaller concentrations. Guanidino acetic acid and guanidino butyric acid were present in normal plasma in quantities not significantly different from those in uremic plasma."}
{"id": "PMID:236103", "title": "[Decrease in serum gamma-glutamyltranspeptidase following abstention from alcohol in cirrhotics (author transl)].", "content": "Gamma-Glutamyltranspeptidase activity of patients having an ascitic cirrhosis due to ethanol consumption is high (139 mU/ml) when the patient is still drinking at the time of the assay; it is lower when the patient had stopped drinking at least two months before the assay (49 mU/ml). On the other hand, in 10 patients out of the 11 who submitted to a second assay gamma-glutamyltranspeptidase decreases as soon as the patient abstains from alcohol. In 4 abstinent patients re-examined one year after the first measurement, the gamma-glutamyltranspeptidase activity had decreased to the reference values of Szasz. The half time of the return to normal has been estimated by extrapolation from the ethylic model at between 11 and 54 days. We conclude that the hyper gamma-glutamyltranspeptidase in cirrhotics is due to the ethanol impregnation and that repeated assays of the enzyme show whether the patient abstains from alcohol or not.", "contents": "[Decrease in serum gamma-glutamyltranspeptidase following abstention from alcohol in cirrhotics (author transl)]. Gamma-Glutamyltranspeptidase activity of patients having an ascitic cirrhosis due to ethanol consumption is high (139 mU/ml) when the patient is still drinking at the time of the assay; it is lower when the patient had stopped drinking at least two months before the assay (49 mU/ml). On the other hand, in 10 patients out of the 11 who submitted to a second assay gamma-glutamyltranspeptidase decreases as soon as the patient abstains from alcohol. In 4 abstinent patients re-examined one year after the first measurement, the gamma-glutamyltranspeptidase activity had decreased to the reference values of Szasz. The half time of the return to normal has been estimated by extrapolation from the ethylic model at between 11 and 54 days. We conclude that the hyper gamma-glutamyltranspeptidase in cirrhotics is due to the ethanol impregnation and that repeated assays of the enzyme show whether the patient abstains from alcohol or not."}
{"id": "PMID:236104", "title": "Fluoride determination in plasma by ion selective electrodes: a simplified method for the clinical laboratory.", "content": "A potentiometric method for the determination of fluoride (F-) in serum and plasma is proposed; it is based on a combination of the single-known-addition method and the electrode slope-by-dilution method. This procedure provides reliable results in extremely low measuring ranges down to 2.5 mug/l, where the electrode slope deviates markedly from Nernstian behaviour. In this method no electrode calibration is required and only one standard is necessary. 1 ml of plasma is sufficient for one analysis. Apart from a 5% enrichment of all samples with a concentrated total ionic strength adjustment buffer, no further preparation of the sample is required. The simplicity of the various pipetting and analytical steps, and also of the evaluation of the readings, may render this method highly suitable for the clinical laboratory. Investigations into the accuracy and precision of the method produced satisfactory results. The recovery in plasma amounted to 99.7%, even in the low measuring ranges. The discrimination capacity of the method amounts to 0.1 mug/l. With the apparatus and experimental procedures described, 18 plasma analyses per day can be performed even at low F- concentrations with which longer electrode stabilization periods are required. Storage of the plasma samples frozen at --20 degrees C for up to 8 weeks exerts no effect on the F- concentration. Problems of sample contamination and other disturbances are discussed. Determinations of normal values in 20 test subjects resulted in a mean value of 10.4 plus or minus 4.01 mug/l (Mean plus or minus S.D.). The modal value amounted to 9.5 mug/l, and the range was between 5.9 and 18.8 mug/l. The F- content of the drinking water supplied to this group of persons amounted to 180 mug/l. The importance of the method has been illustrated using a clinico-nephrological study as an example.", "contents": "Fluoride determination in plasma by ion selective electrodes: a simplified method for the clinical laboratory. A potentiometric method for the determination of fluoride (F-) in serum and plasma is proposed; it is based on a combination of the single-known-addition method and the electrode slope-by-dilution method. This procedure provides reliable results in extremely low measuring ranges down to 2.5 mug/l, where the electrode slope deviates markedly from Nernstian behaviour. In this method no electrode calibration is required and only one standard is necessary. 1 ml of plasma is sufficient for one analysis. Apart from a 5% enrichment of all samples with a concentrated total ionic strength adjustment buffer, no further preparation of the sample is required. The simplicity of the various pipetting and analytical steps, and also of the evaluation of the readings, may render this method highly suitable for the clinical laboratory. Investigations into the accuracy and precision of the method produced satisfactory results. The recovery in plasma amounted to 99.7%, even in the low measuring ranges. The discrimination capacity of the method amounts to 0.1 mug/l. With the apparatus and experimental procedures described, 18 plasma analyses per day can be performed even at low F- concentrations with which longer electrode stabilization periods are required. Storage of the plasma samples frozen at --20 degrees C for up to 8 weeks exerts no effect on the F- concentration. Problems of sample contamination and other disturbances are discussed. Determinations of normal values in 20 test subjects resulted in a mean value of 10.4 plus or minus 4.01 mug/l (Mean plus or minus S.D.). The modal value amounted to 9.5 mug/l, and the range was between 5.9 and 18.8 mug/l. The F- content of the drinking water supplied to this group of persons amounted to 180 mug/l. The importance of the method has been illustrated using a clinico-nephrological study as an example."}
{"id": "PMID:236105", "title": "Separation of human alpha-amylase isozymes by electro-focusing and their immunological properties.", "content": "Human alpha-amylase (alpha-1,4-glucan-4-glucanohydrolase, EC 3.2.1.1) was separated by electrofocusing. The amylases in serum and urine were seperated into two major isozymes with isoelectric points of pH 6.4-6.5 and pH 6.9-7.0, respectively, and one minor isozyme with an isoelectric point of pH 5.9. The amylases in saliva were separated into one major isozyme with an isoelectric point of pH 6.5 and two minor isozymes with isoelectric points of pH 6.0 and 6.9. The amylases in pancreatic juice gave one major peak at pH 7.0 and two minor peaks at pH 6.0 and pH 6.5. Repeated electrofocusing of each isozyme have only a single peak with a constant isoelectric point. The antigenicites of these three isozymes were also investigated using antisera to rat pancreatic and parotid amylases.", "contents": "Separation of human alpha-amylase isozymes by electro-focusing and their immunological properties. Human alpha-amylase (alpha-1,4-glucan-4-glucanohydrolase, EC 3.2.1.1) was separated by electrofocusing. The amylases in serum and urine were seperated into two major isozymes with isoelectric points of pH 6.4-6.5 and pH 6.9-7.0, respectively, and one minor isozyme with an isoelectric point of pH 5.9. The amylases in saliva were separated into one major isozyme with an isoelectric point of pH 6.5 and two minor isozymes with isoelectric points of pH 6.0 and 6.9. The amylases in pancreatic juice gave one major peak at pH 7.0 and two minor peaks at pH 6.0 and pH 6.5. Repeated electrofocusing of each isozyme have only a single peak with a constant isoelectric point. The antigenicites of these three isozymes were also investigated using antisera to rat pancreatic and parotid amylases."}
{"id": "PMID:236106", "title": "Linkage investigation of a large family with Reifenstein's syndrome.", "content": "Linkage analysis of a 116-member family with 11 males affected by Reifenstein's syndrome is reported. One X-chromosomal and eight autosomal markers were used. Close linkage can be excluded for P, K, MNS and Xg-a. A possibility of close linkage to ABO is discussed.", "contents": "Linkage investigation of a large family with Reifenstein's syndrome. Linkage analysis of a 116-member family with 11 males affected by Reifenstein's syndrome is reported. One X-chromosomal and eight autosomal markers were used. Close linkage can be excluded for P, K, MNS and Xg-a. A possibility of close linkage to ABO is discussed."}
{"id": "PMID:236108", "title": "Comparison of the hypnotic activity of triazolam, flurazepam hydrochloride, and placebo.", "content": "Triazolam, 0.4 and 0.8 mg, flurazepam, 15 and 30 mg, and placebo were compared in a double-blind, randomized 5-night crossover study in 25 inpatient insomniacs. These patients all complained difficulty falling asleep; all said they usually slept less than 5 hr a nigh and woke up too early in the morning. Results of the patients' global evaluation of the medications shows that all of the treatments were rated significantly higher than placebo, with the exception of triazolam, 0.4 mg, which was not significantly different from flurazepam, 15 or 30 mg, or from placebo. In subjective evaluation of sleep onset, only triazolam, 0.4 and 0.8 mg, was rated faster than placebo. All 4 active medications increased duration of sleep. Triazolam, 0.8 mg, and flurazepam, 30 mg, were rated as providing deeper sleep than placebo while all treatments except flurazepam, 15 mg, decreased the number of awakenings below that on placebo. A significant dose-response curve was obtained with triazolam and flurazepam for some of the parameters. Very few adverse effects were reported. One patient reported feeling groggy and drowsy on 0.4 mg triazolam while 2 reported nightmares on placebo.", "contents": "Comparison of the hypnotic activity of triazolam, flurazepam hydrochloride, and placebo. Triazolam, 0.4 and 0.8 mg, flurazepam, 15 and 30 mg, and placebo were compared in a double-blind, randomized 5-night crossover study in 25 inpatient insomniacs. These patients all complained difficulty falling asleep; all said they usually slept less than 5 hr a nigh and woke up too early in the morning. Results of the patients' global evaluation of the medications shows that all of the treatments were rated significantly higher than placebo, with the exception of triazolam, 0.4 mg, which was not significantly different from flurazepam, 15 or 30 mg, or from placebo. In subjective evaluation of sleep onset, only triazolam, 0.4 and 0.8 mg, was rated faster than placebo. All 4 active medications increased duration of sleep. Triazolam, 0.8 mg, and flurazepam, 30 mg, were rated as providing deeper sleep than placebo while all treatments except flurazepam, 15 mg, decreased the number of awakenings below that on placebo. A significant dose-response curve was obtained with triazolam and flurazepam for some of the parameters. Very few adverse effects were reported. One patient reported feeling groggy and drowsy on 0.4 mg triazolam while 2 reported nightmares on placebo."}
{"id": "PMID:236109", "title": "Effects of intravenous and oral propantheline and metoclopramide on ethanol absorption.", "content": "The separate effects of propantheline, atropine, and metoclopramide on ethanol absorption have been studied in man. Intravenous propantheline lowered blood ethanol levels after ingestion of a standard ethanol load. Oral propantheline, at dose levels currently recommended for therapeutic use, was without significant effect on ethanol tolerance, whereas the tolerance was reduced by oral atropine. Propantheline bromide tablets have been shown to undergo significant hydrolysis at alkaline pH in vitro. Metoclopramide, given intravenously and orally, significant elevated blood ethanol levels soon after ingestion of a standard ethanol load. It is suggested that when propantheline is selected as an anticholinergic for clinical use, there is need for greater awareness of the marked reduction in bioavailablity that results when the drug is administered at conventional therapeutic dosage by the oral as opposed to the intravenous route.", "contents": "Effects of intravenous and oral propantheline and metoclopramide on ethanol absorption. The separate effects of propantheline, atropine, and metoclopramide on ethanol absorption have been studied in man. Intravenous propantheline lowered blood ethanol levels after ingestion of a standard ethanol load. Oral propantheline, at dose levels currently recommended for therapeutic use, was without significant effect on ethanol tolerance, whereas the tolerance was reduced by oral atropine. Propantheline bromide tablets have been shown to undergo significant hydrolysis at alkaline pH in vitro. Metoclopramide, given intravenously and orally, significant elevated blood ethanol levels soon after ingestion of a standard ethanol load. It is suggested that when propantheline is selected as an anticholinergic for clinical use, there is need for greater awareness of the marked reduction in bioavailablity that results when the drug is administered at conventional therapeutic dosage by the oral as opposed to the intravenous route."}
{"id": "PMID:236110", "title": "Ammonia and urea transport by the excluded human colon.", "content": "1. Ammonia and urea transport across the colonic mucosa was studied by a perfusion technique in four subjects with colonic exclusion for chronic hepatic encephalopathy. 2. Reduction of luminal pH inhibited net and unidirectional transport of ammonia from lumen to plasma, but net absorption from high luminal concentrations persisted at low pH. 3. Neither addition of urea to the perfusate nor intravenous infusion of urea produced a consistent increase in the colonic excretion of ammonia when ammonia-free solutions were perfused. 4. In one subject intravenous infusion of (15N)-ammonium chloride produced rapid labelling of colonic effluent ammonia and within 60 min the specific enrichments of ammonia in effluent and in arterial plasma were approximately equal. 5. During perfusion of nitrogen-free solutions, only small amounts of urea appeared in the effluent, suggesing limited permeability of the colonic mucosa to urea. 6. These results are discussed in relation to the equilibration of ammonia across the colonic mucosa by both ionic and non-ionic diffusion. The lack of evidence of 'juxtamucosal' (as opposed to luminal) ureolysis is in contrast to other observations on the intact colon. The possible reasons for and implications of this discrepancy are discussed.", "contents": "Ammonia and urea transport by the excluded human colon. 1. Ammonia and urea transport across the colonic mucosa was studied by a perfusion technique in four subjects with colonic exclusion for chronic hepatic encephalopathy. 2. Reduction of luminal pH inhibited net and unidirectional transport of ammonia from lumen to plasma, but net absorption from high luminal concentrations persisted at low pH. 3. Neither addition of urea to the perfusate nor intravenous infusion of urea produced a consistent increase in the colonic excretion of ammonia when ammonia-free solutions were perfused. 4. In one subject intravenous infusion of (15N)-ammonium chloride produced rapid labelling of colonic effluent ammonia and within 60 min the specific enrichments of ammonia in effluent and in arterial plasma were approximately equal. 5. During perfusion of nitrogen-free solutions, only small amounts of urea appeared in the effluent, suggesing limited permeability of the colonic mucosa to urea. 6. These results are discussed in relation to the equilibration of ammonia across the colonic mucosa by both ionic and non-ionic diffusion. The lack of evidence of 'juxtamucosal' (as opposed to luminal) ureolysis is in contrast to other observations on the intact colon. The possible reasons for and implications of this discrepancy are discussed."}
{"id": "PMID:236111", "title": "Effect of bile-duct ligation on organelle marker enzymes in the liver and serum of rats.", "content": "1. Marker enzymes for the principal subcellular organelles of rat liver were asayed in the liver of rats 1 day and 8 days after bile-duct ligation or after laparotomy as a control procedure. 2. The microsomal enzymes in liver tissue showed complex changes. Benz[alpha]pyrene hydroxylase activity, predominantly found in the smooth endoplasmic reticulum, was decreased. Glucose 6-phosphatase activity and ribonucleic acid, which are localized predominantly in the rough endoplasmic reticulum, were increased. 3. The plasma membrane enzyme, alkaline phosphatase, increased in activity after bile-duct ligation. 4. No changes in mitochondrial enzyme activities were noted after 1 day but there was a 50% reduction 8 days after ligation. Lysosomal enzyme activities did not change in the liver tissue. 5. Liver catalase and D-amino acid oxidase activities showed a slight increase at 1 day postligation but a significant fall by 8 days. 6. Lactate dehydrogenase, a cytosol enzyme, showed a decrease in activity after 1 day but an increase in tissue activities 8 days after ligation. 7. Serum activities of mitochondrial, plasma membrane, microsomal, lysosomal and cytosol marker enzymes tended to increase post-ligation, particularly at 8 days. 8. Monoamine oxidase, a predominantly mitochondrial enzyme, was greatly elevated in the serum after 1 day but had returned to normal activities by 8 days.", "contents": "Effect of bile-duct ligation on organelle marker enzymes in the liver and serum of rats. 1. Marker enzymes for the principal subcellular organelles of rat liver were asayed in the liver of rats 1 day and 8 days after bile-duct ligation or after laparotomy as a control procedure. 2. The microsomal enzymes in liver tissue showed complex changes. Benz[alpha]pyrene hydroxylase activity, predominantly found in the smooth endoplasmic reticulum, was decreased. Glucose 6-phosphatase activity and ribonucleic acid, which are localized predominantly in the rough endoplasmic reticulum, were increased. 3. The plasma membrane enzyme, alkaline phosphatase, increased in activity after bile-duct ligation. 4. No changes in mitochondrial enzyme activities were noted after 1 day but there was a 50% reduction 8 days after ligation. Lysosomal enzyme activities did not change in the liver tissue. 5. Liver catalase and D-amino acid oxidase activities showed a slight increase at 1 day postligation but a significant fall by 8 days. 6. Lactate dehydrogenase, a cytosol enzyme, showed a decrease in activity after 1 day but an increase in tissue activities 8 days after ligation. 7. Serum activities of mitochondrial, plasma membrane, microsomal, lysosomal and cytosol marker enzymes tended to increase post-ligation, particularly at 8 days. 8. Monoamine oxidase, a predominantly mitochondrial enzyme, was greatly elevated in the serum after 1 day but had returned to normal activities by 8 days."}
{"id": "PMID:236147", "title": "Intestinal obstruction in the horse. Physical signs and blood chemistry.", "content": "Physical signs and blood changes were studied in horses with artificially produced obstructions of the duodenum and the small colon and simulated volvulus of the ileum. Horses with obstruction of the duodenum had the most violent physical signs and the shortest survival time. Blood changes were an initial rise in pH followed by acidosis, hyperkalemia and a decrease in HCO3 minus, Na+ and C1 minus. Obstruction of the small colon resulted in mild physical signs. The blood parameters recorded were normal. Simulated volvulus resulted in continuous colic. Blood changes were acidosis and hyperkalemia with a continuous decrease in HCO3 minus and C1 minus levels.", "contents": "Intestinal obstruction in the horse. Physical signs and blood chemistry. Physical signs and blood changes were studied in horses with artificially produced obstructions of the duodenum and the small colon and simulated volvulus of the ileum. Horses with obstruction of the duodenum had the most violent physical signs and the shortest survival time. Blood changes were an initial rise in pH followed by acidosis, hyperkalemia and a decrease in HCO3 minus, Na+ and C1 minus. Obstruction of the small colon resulted in mild physical signs. The blood parameters recorded were normal. Simulated volvulus resulted in continuous colic. Blood changes were acidosis and hyperkalemia with a continuous decrease in HCO3 minus and C1 minus levels."}
{"id": "PMID:236148", "title": "Pathogenesis of lead shot poisoning in the mallard duck.", "content": "Adult mallard ducks were administered steel pellets to determine the rate of excretion from the gastrointestinal tract. In separate studies the ducks were administered 5 number 6 lead pellets. Birds were examined for clinical signs and sacrificed at given intervals over a 20 day period to assess changes in tissue structure and concentrations of lead with time. The above studies were conducted in 2 groups of ducks, fed a low or a high fiber diet. The rate of steel pellet excretion on birds on the low fiber diet decreased with an increase in pellet size. Pellet excretion was greatly reduced in birds fed the high fiber diet. Administration of lead shot resulted in the development of green diarrhea, anorexia and weakness. It also produced high concentrations of lead in the blood, kidney, liver and bone with lower concentrations in skeletal muscle. The major lesions were destruction of the mitotically active proventricular epithelium and medullary osteocytes, destruction of pectoral muscle cells and the presence of intranuclear inclusion bodies in the proximal tubular epithelium of the kidneys. Birds on the high fiber diet demonstrated more severe clinical signs and higher concentrations of lead in the tissues.", "contents": "Pathogenesis of lead shot poisoning in the mallard duck. Adult mallard ducks were administered steel pellets to determine the rate of excretion from the gastrointestinal tract. In separate studies the ducks were administered 5 number 6 lead pellets. Birds were examined for clinical signs and sacrificed at given intervals over a 20 day period to assess changes in tissue structure and concentrations of lead with time. The above studies were conducted in 2 groups of ducks, fed a low or a high fiber diet. The rate of steel pellet excretion on birds on the low fiber diet decreased with an increase in pellet size. Pellet excretion was greatly reduced in birds fed the high fiber diet. Administration of lead shot resulted in the development of green diarrhea, anorexia and weakness. It also produced high concentrations of lead in the blood, kidney, liver and bone with lower concentrations in skeletal muscle. The major lesions were destruction of the mitotically active proventricular epithelium and medullary osteocytes, destruction of pectoral muscle cells and the presence of intranuclear inclusion bodies in the proximal tubular epithelium of the kidneys. Birds on the high fiber diet demonstrated more severe clinical signs and higher concentrations of lead in the tissues."}
{"id": "PMID:236149", "title": "Respirator weaning of the newborn: some practical considerations.", "content": "Weaning of neonates from assisted ventilation or continous positive pressure breathing is a complex process. Unfortunately, at present we lack sensitive indices to measure the infant's ability to sustain spontaneous breathing. In the absence of such criteria we should rely heavily on clinical findings correlated with available biochemical data. Good clinical acumen and experience is necessary for successful weaning.", "contents": "Respirator weaning of the newborn: some practical considerations. Weaning of neonates from assisted ventilation or continous positive pressure breathing is a complex process. Unfortunately, at present we lack sensitive indices to measure the infant's ability to sustain spontaneous breathing. In the absence of such criteria we should rely heavily on clinical findings correlated with available biochemical data. Good clinical acumen and experience is necessary for successful weaning."}
{"id": "PMID:236156", "title": "Metabolism of dihalomethanes to carbon monoxide. II. In vitro studies.", "content": "Dibromomethane was metabolized to carbon monoxide and inorganic bromide by a rat liver microsomal fraction requiring both NADPH and molecular oxygen. This biotransformation was characterized with respect to time course, microsomal protein concentration, pH, and temperature. The metabolism of dihalomethanes to carbon monoxide followed the halide order; thus, diiodomethane yielded the greatest amount of carbon monoxide, whereas dichloromethane yielded the smallest amount. A KM of approximately 16 mM was established for dibromomethane while the Vmax was found to be about 8 nmol of CO per mg of microsomal protein per min. Cytochrome P-450 was found to bind dibromomethane to produce a type I binding spectrum. Pretreatment with phenobarbital increased both microsomal cytochrome P-450 levels and the rate of conversion of dibromomethane to carbon monoxide. Pretreatment with cobaltous chloride or storage of microsomal preparations at 4 degrees C resulted in parallel reductions of both cytochrome P-450 levels and the rate of formation of carbon monoxide from dibromomethane. SKF 525-A, ethylmorphine, and hexobarbital inhibited the conversion of dibromomethane to carbon monoxide. Microsomal preparations from rat lung metabolized this substrate at about 18% of the rate found in liver microsomes. The requirement for both NADPH and molecular oxygen, the inhibitory effects of SKF 525-A, ethylmorphine, and hexobarbital on the production of carbon monoxide from dibromomethane, and the correlation established between microsomal cytochrome P-450 levels and the rate of metabolism of dihalomethanes to carbon monoxide after treatments that alter the cytochrome to P-450 content suggest that these compounds are metabolized to carbon monoxide via a cytochrome P-450-dependent system.", "contents": "Metabolism of dihalomethanes to carbon monoxide. II. In vitro studies. Dibromomethane was metabolized to carbon monoxide and inorganic bromide by a rat liver microsomal fraction requiring both NADPH and molecular oxygen. This biotransformation was characterized with respect to time course, microsomal protein concentration, pH, and temperature. The metabolism of dihalomethanes to carbon monoxide followed the halide order; thus, diiodomethane yielded the greatest amount of carbon monoxide, whereas dichloromethane yielded the smallest amount. A KM of approximately 16 mM was established for dibromomethane while the Vmax was found to be about 8 nmol of CO per mg of microsomal protein per min. Cytochrome P-450 was found to bind dibromomethane to produce a type I binding spectrum. Pretreatment with phenobarbital increased both microsomal cytochrome P-450 levels and the rate of conversion of dibromomethane to carbon monoxide. Pretreatment with cobaltous chloride or storage of microsomal preparations at 4 degrees C resulted in parallel reductions of both cytochrome P-450 levels and the rate of formation of carbon monoxide from dibromomethane. SKF 525-A, ethylmorphine, and hexobarbital inhibited the conversion of dibromomethane to carbon monoxide. Microsomal preparations from rat lung metabolized this substrate at about 18% of the rate found in liver microsomes. The requirement for both NADPH and molecular oxygen, the inhibitory effects of SKF 525-A, ethylmorphine, and hexobarbital on the production of carbon monoxide from dibromomethane, and the correlation established between microsomal cytochrome P-450 levels and the rate of metabolism of dihalomethanes to carbon monoxide after treatments that alter the cytochrome to P-450 content suggest that these compounds are metabolized to carbon monoxide via a cytochrome P-450-dependent system."}
{"id": "PMID:236157", "title": "Metabolism of R-(+)-and S-(minus)-pentobarbital by hepatic microsomes from male rats.", "content": "Hepatic microsomes from male rats hydroxylate R-(+)- and (-)-[2-14-C]pentobarbital to the diasterioisomeric 3'-alcohols: metabolite I (1'RS, 3'SR)- and metabolite II (1'RS, 3'RS)-5-ethyl-5-(3'-hydroxy-1'methylbutyl) barbituric acids. The rate is linear up to 1.5 mg of microsomal protein per ml of incubation mixture and for up to 16 min. The metabolism of R-(+)-pentobarbital led to production of nearly equal quantities of metabolites I and II with a total hydroxylation of 1.08 nmol/min/mg of protein. On the other hand, the S-(-) pentobarbital gave 3- to 5-fold less of metabolite I than II and a total hydroxylation of 1.42 nmol/min/mg of protein. The KM values for formation of metabolite I were 381 muM from R-(+)- and 241 muM from the S-(-)-pentobarbital, while for metabolite II they were 115 muM from R-(+)- and 68 muM from S-(-)-pentobarbital. These data suggest that there are at least two enzymes catalyzing the hydroxylation of pentobarbital, one to give metabolite II and another or others to give metabolite I.", "contents": "Metabolism of R-(+)-and S-(minus)-pentobarbital by hepatic microsomes from male rats. Hepatic microsomes from male rats hydroxylate R-(+)- and (-)-[2-14-C]pentobarbital to the diasterioisomeric 3'-alcohols: metabolite I (1'RS, 3'SR)- and metabolite II (1'RS, 3'RS)-5-ethyl-5-(3'-hydroxy-1'methylbutyl) barbituric acids. The rate is linear up to 1.5 mg of microsomal protein per ml of incubation mixture and for up to 16 min. The metabolism of R-(+)-pentobarbital led to production of nearly equal quantities of metabolites I and II with a total hydroxylation of 1.08 nmol/min/mg of protein. On the other hand, the S-(-) pentobarbital gave 3- to 5-fold less of metabolite I than II and a total hydroxylation of 1.42 nmol/min/mg of protein. The KM values for formation of metabolite I were 381 muM from R-(+)- and 241 muM from the S-(-)-pentobarbital, while for metabolite II they were 115 muM from R-(+)- and 68 muM from S-(-)-pentobarbital. These data suggest that there are at least two enzymes catalyzing the hydroxylation of pentobarbital, one to give metabolite II and another or others to give metabolite I."}
{"id": "PMID:236159", "title": "The metabolism and disposition of aniline in the isolated blood-perfused liver of the rat.", "content": "In the isolated, blood-perfused liver of the rat, aniline is removed from the perfusion medium rapidly over the first 60 min, but more slowly over the following 120 min. The main metabolite found in the perfusion medium is an acid-labile conjugate of aniline which after 3 hr accounts for 33% of the aniline added, whereas p-aminophenol conjugates account for a further 13%. No free p-aminophenol could be detected in the perfusion medium and only a small amount in the bile. Aniline conjugates form the major metabolites found in the bile. A kinetic analysis of the data is presented and a two-compartment model is postulated in which aniline is removed for excretion in the bile or for metabolism from the first compartment. SKF 525-A, 0.2 mM, completely blocks the formation of p-aminophenol and inhibits the formation of the acid-labile aniline conjugate by 62%. There is also an increase in the size of the second compartment.", "contents": "The metabolism and disposition of aniline in the isolated blood-perfused liver of the rat. In the isolated, blood-perfused liver of the rat, aniline is removed from the perfusion medium rapidly over the first 60 min, but more slowly over the following 120 min. The main metabolite found in the perfusion medium is an acid-labile conjugate of aniline which after 3 hr accounts for 33% of the aniline added, whereas p-aminophenol conjugates account for a further 13%. No free p-aminophenol could be detected in the perfusion medium and only a small amount in the bile. Aniline conjugates form the major metabolites found in the bile. A kinetic analysis of the data is presented and a two-compartment model is postulated in which aniline is removed for excretion in the bile or for metabolism from the first compartment. SKF 525-A, 0.2 mM, completely blocks the formation of p-aminophenol and inhibits the formation of the acid-labile aniline conjugate by 62%. There is also an increase in the size of the second compartment."}
{"id": "PMID:236158", "title": "Reconstitution of the rabbit pulmonary microsomal mixed-function oxidase system from solubilized components.", "content": "Lung microsomal cytochrome P-450 was solubilized and purified 2-fold. NADPH-cytochrome c reductase (EC 1.6.2.3) was solubilized and purified 4-6 fold by three methods with use of sonication and detergent digestion followed by either DEAE-cellulose chromatography or ammonium sulfate fractionation. Benzphetamine N-demethylase and 7-ethoxycoumarin deethylase activities were reconstituted when NADPH-cytochrome c reductase and cytochrome P-450 fractions were combined. Reductase fractions prepared by sodium cholate digestion of microsomes were highly active in supporting the hydroxylation activity in the reconstituted systems, whereas those prepared with sodium deoxycholate were not. About twice as much NADPH-cytochrome c reductase was required for saturation of the 7-ethoxycoumarin deethylase activity as for saturation of the benzphetamine N-demethylase activity. A heat-stable lipid fraction was necessary for maximum hydroxylation activity. NADH did not support benzphetamine N-demethylation in the reconstituted system or increase the rate of reaction when added with NADPH.", "contents": "Reconstitution of the rabbit pulmonary microsomal mixed-function oxidase system from solubilized components. Lung microsomal cytochrome P-450 was solubilized and purified 2-fold. NADPH-cytochrome c reductase (EC 1.6.2.3) was solubilized and purified 4-6 fold by three methods with use of sonication and detergent digestion followed by either DEAE-cellulose chromatography or ammonium sulfate fractionation. Benzphetamine N-demethylase and 7-ethoxycoumarin deethylase activities were reconstituted when NADPH-cytochrome c reductase and cytochrome P-450 fractions were combined. Reductase fractions prepared by sodium cholate digestion of microsomes were highly active in supporting the hydroxylation activity in the reconstituted systems, whereas those prepared with sodium deoxycholate were not. About twice as much NADPH-cytochrome c reductase was required for saturation of the 7-ethoxycoumarin deethylase activity as for saturation of the benzphetamine N-demethylase activity. A heat-stable lipid fraction was necessary for maximum hydroxylation activity. NADH did not support benzphetamine N-demethylation in the reconstituted system or increase the rate of reaction when added with NADPH."}
{"id": "PMID:236160", "title": "Biliary excretion of diphenylhydantoin in the rat. Time-course studies.", "content": "The role of biliary excretion in the dose-dependent elimination of diphenylhydantoin (DPH) was investigated in the rat. During 6 hr, following iv injection of 10 mg of (14-C)DPH per kg, 28% of the radioactivity was excreted in bile and following the higher dose of DPH reached a plateau and remained constant over a period of 6 hr, whereas, with the lower dose, the excretion was a first order process (half-life 165 plus or minus 34 (SE) min). When the major metabolite of DPH,5-(P-hydroxyphenyl)-5-phenylhydantoin (P-HPPH, 14-C-labeled), was administered 1 and 10 mg/kg iv), the rates of biliary excretion of total radioactivity were first order, with half-lives of 49 plus or minus 3 and 57 plus or minus 4 min, respectively. Therefore, the conjugation of p-HPPH and the transfer of the conjugate from liver cells into bile were not saturable with the two doses studied. The data are consistent with the assumption that the dose-dependent elimination of DPH is due to the saturable conversion of DPH to p-HPPH.", "contents": "Biliary excretion of diphenylhydantoin in the rat. Time-course studies. The role of biliary excretion in the dose-dependent elimination of diphenylhydantoin (DPH) was investigated in the rat. During 6 hr, following iv injection of 10 mg of (14-C)DPH per kg, 28% of the radioactivity was excreted in bile and following the higher dose of DPH reached a plateau and remained constant over a period of 6 hr, whereas, with the lower dose, the excretion was a first order process (half-life 165 plus or minus 34 (SE) min). When the major metabolite of DPH,5-(P-hydroxyphenyl)-5-phenylhydantoin (P-HPPH, 14-C-labeled), was administered 1 and 10 mg/kg iv), the rates of biliary excretion of total radioactivity were first order, with half-lives of 49 plus or minus 3 and 57 plus or minus 4 min, respectively. Therefore, the conjugation of p-HPPH and the transfer of the conjugate from liver cells into bile were not saturable with the two doses studied. The data are consistent with the assumption that the dose-dependent elimination of DPH is due to the saturable conversion of DPH to p-HPPH."}
{"id": "PMID:236161", "title": "The uptake and distribution of 14-C-mescaline in different organs of developing rat.", "content": "Rats of 1,4,8,12,20, and 60 days postnatal age were injected ip with 14-C-mescaline (50 nCi/g). The levels of mescaline and its deaminated metabolite, 3,4,5-trimethoxyphenylacetic acid, were examined in the brain, liver, heart, spleen, lung, and kidney at 30, 60, 90, and 120 min. Mescaline was rapidly taken up by all the organs examined. In general, the organs of younger rats accumulated much larger amounts than those of adult animals. Brain concentrated the lowest amounts in comparison with other tissues. In the brain, the uptake was the highest in 1-day-old rats and decreased with age. The disappearance of mescaline in various organs was comparatively slower in younger animals than in 20-day or older rats. Rats immediately after birth and uptake was the highest in 1-day-old rats and decreased with age. The disappearance of mescaline in various organs was comparatively slower in younger animals than in 20-day or older rats. Rats immediately after birth and up to 20 days of age metabolized mescaline less efficiently than adults. From the data, it appears that the blood-brain barrier for mescaline develops gradually with age but is not completely impermeable in adults.", "contents": "The uptake and distribution of 14-C-mescaline in different organs of developing rat. Rats of 1,4,8,12,20, and 60 days postnatal age were injected ip with 14-C-mescaline (50 nCi/g). The levels of mescaline and its deaminated metabolite, 3,4,5-trimethoxyphenylacetic acid, were examined in the brain, liver, heart, spleen, lung, and kidney at 30, 60, 90, and 120 min. Mescaline was rapidly taken up by all the organs examined. In general, the organs of younger rats accumulated much larger amounts than those of adult animals. Brain concentrated the lowest amounts in comparison with other tissues. In the brain, the uptake was the highest in 1-day-old rats and decreased with age. The disappearance of mescaline in various organs was comparatively slower in younger animals than in 20-day or older rats. Rats immediately after birth and uptake was the highest in 1-day-old rats and decreased with age. The disappearance of mescaline in various organs was comparatively slower in younger animals than in 20-day or older rats. Rats immediately after birth and up to 20 days of age metabolized mescaline less efficiently than adults. From the data, it appears that the blood-brain barrier for mescaline develops gradually with age but is not completely impermeable in adults."}
{"id": "PMID:236162", "title": "Epoxide metabolites of protriptyline in rat urine.", "content": "Two epoxide metabolites of 5-(3-methylaminopropyl)-5H-dibenzo[a,d]cycloheptene (protriptyline) were identified in the urine of rats given 14-C-labeled drug. They were characterized by mass spectrometry, nuclear magnetic resonance spectrometry, and chemical reactivity as 10,11-dihydro-10,11-epoxy-5(3-methylaminopropyl)-5H-dibenzo[a,d]cycloheptene (I) and 10,11-dihydro-10,11-epoxy-5(3-aminopropyl)-5H-dibenzo[a,d]cycloheptene (II). Over twice as much I as II was excreted and together the two metabolites accounted for approximately 40% of the urinary radioactivity.", "contents": "Epoxide metabolites of protriptyline in rat urine. Two epoxide metabolites of 5-(3-methylaminopropyl)-5H-dibenzo[a,d]cycloheptene (protriptyline) were identified in the urine of rats given 14-C-labeled drug. They were characterized by mass spectrometry, nuclear magnetic resonance spectrometry, and chemical reactivity as 10,11-dihydro-10,11-epoxy-5(3-methylaminopropyl)-5H-dibenzo[a,d]cycloheptene (I) and 10,11-dihydro-10,11-epoxy-5(3-aminopropyl)-5H-dibenzo[a,d]cycloheptene (II). Over twice as much I as II was excreted and together the two metabolites accounted for approximately 40% of the urinary radioactivity."}
{"id": "PMID:236163", "title": "Lorazepam: glucuronide formation in the cat.", "content": "The excretion and metabolism of lorazepam was studied in domestic cats. After oral administration of 14-C-lorazepam (1 mg/kg), the mean percent of the dose excreted in urine was 47.3 plus or minus 6.7% (SD) and in feces 54.0 plus or minus 6.1% (SD). The main urinary metabolite was lorazepam glucuronide; its mean excretion over the first 3 days amounted to 29% of the dose (66% of urinary radioactivity). When 20 mg of unlabeled drug per kg was given, about 40% of the dose was excreted into urine as lorazepam glucuronide within 6 days. Conculsive evidence for the glucuronide structure was obtained by chemical analysis and mass spectrometry of the lorazepam conjugate isolated from cat urine. The radioactivity in urine which was not attributable to several minor metabolites. In plasma, both lorazepam and lorazepam glucuronide were present. These findings indicate that the cat is capable of using glucuronidation as a major route of conjugation, contrary to the many reports that cats conjugate exogenous materials poorly with glucuronic acid.", "contents": "Lorazepam: glucuronide formation in the cat. The excretion and metabolism of lorazepam was studied in domestic cats. After oral administration of 14-C-lorazepam (1 mg/kg), the mean percent of the dose excreted in urine was 47.3 plus or minus 6.7% (SD) and in feces 54.0 plus or minus 6.1% (SD). The main urinary metabolite was lorazepam glucuronide; its mean excretion over the first 3 days amounted to 29% of the dose (66% of urinary radioactivity). When 20 mg of unlabeled drug per kg was given, about 40% of the dose was excreted into urine as lorazepam glucuronide within 6 days. Conculsive evidence for the glucuronide structure was obtained by chemical analysis and mass spectrometry of the lorazepam conjugate isolated from cat urine. The radioactivity in urine which was not attributable to several minor metabolites. In plasma, both lorazepam and lorazepam glucuronide were present. These findings indicate that the cat is capable of using glucuronidation as a major route of conjugation, contrary to the many reports that cats conjugate exogenous materials poorly with glucuronic acid."}
{"id": "PMID:236167", "title": "Timolol: a preliminary report of its pharmacological properties and therapeutic efficacy in angina and hypertension.", "content": "Timolol (MK 950) is a new beta-adrenergic receptor blocking drug. It has little or no membrane stabilising ('quinidine-like') or partial agonist (intrinsic sympathomimetic) activity and thus resembles sotalol. On a weight for.weight basis, timolol is more potent than sotalol or propranolol. A 2.5 mg dose of timolol causes about the same reduction in resting heart rate as 20mg of propranolol. Results of placebo-controlled and of comparative trials with other beta-adrenergic receptor blocking drugs, have shown that timolol effectively lowers blood pressure without producing orthostatic or exercise hypotension. Findings of an international multicentre trial in angina pectoris, indicate that timolol is effective in reducing the frequency of anginal attacks and the consumption of glyceryl trinitrate for their relief.", "contents": "Timolol: a preliminary report of its pharmacological properties and therapeutic efficacy in angina and hypertension. Timolol (MK 950) is a new beta-adrenergic receptor blocking drug. It has little or no membrane stabilising ('quinidine-like') or partial agonist (intrinsic sympathomimetic) activity and thus resembles sotalol. On a weight for.weight basis, timolol is more potent than sotalol or propranolol. A 2.5 mg dose of timolol causes about the same reduction in resting heart rate as 20mg of propranolol. Results of placebo-controlled and of comparative trials with other beta-adrenergic receptor blocking drugs, have shown that timolol effectively lowers blood pressure without producing orthostatic or exercise hypotension. Findings of an international multicentre trial in angina pectoris, indicate that timolol is effective in reducing the frequency of anginal attacks and the consumption of glyceryl trinitrate for their relief."}
{"id": "PMID:236164", "title": "Metabolism and disposition of N-(4-(5-nitro-2-furyl)-(2-14-C)thiazolyl)acetamide in the rat.", "content": "The metabolism of N-[4-(5-nitro-2-furyl)-2-thiazolyl]acetamide (NFTA), a carcinogen for the mouse, rat, dog, and hamster, was investigated in the rat. Radioactive NFTA administered ip to young and lactating female rats was rapidly absorbed through the peritoneum and deposited in the urine, intestinal contents, and feces. Less than 0.5% of the radioactivity was expired as CO2 during the first 24 hr. Two yellow metabolites, accounting for 5 and 27% of the radioactivity in the urine, were found by paper chromatography. One metabolite retained the 2-amino-4-(5-nitro-2-furyl)thiazole moiety. Less than 0.5% of the radioactivity in the urine was due to unchanged 14-C-NFTA. The radioactivity level in the visceral organs reached a maximum 2 hr after dosing and then gradually decreased. Liver contained considerably more radioactivity than did other visceral organs; this was mainly distributed in the cytosol and 900g pellets. Fifty per cent of the radioactivity in the liver was bound to the hot trichloroacetic acid (TCA)-insoluble fraction; that bound to the cold TCA-insoluble fraction increased gradually from 66.9% at 2 hr to 82.6% at 24 hr. The radioactivity bound to the cold and hot TCA-insoluble fractions in kidney remained at 30% and 20%, respectively. Nitroreduction of 14-C-NFTA by microsomes, as a prerequisite of the binding of metabolite to microsomal protein, was demonstrated. Addition of L-cysteine or reduced glutathione to the incubation mixture did not alter the nitroreductase activity of the microsomes; however, binding of radioactivity to protein was significantly decreased. Addition of other amino acids did not significantly decrease the nitroreductase activity or binding to protein. These results suggest that reduced NFTA binds to the protein sulfhydryl groups. Since 14-C-NFTA binds to macromolecules in vivo,nitroreductionmay be important for the metabolism of 5-nitrofurans.", "contents": "Metabolism and disposition of N-(4-(5-nitro-2-furyl)-(2-14-C)thiazolyl)acetamide in the rat. The metabolism of N-[4-(5-nitro-2-furyl)-2-thiazolyl]acetamide (NFTA), a carcinogen for the mouse, rat, dog, and hamster, was investigated in the rat. Radioactive NFTA administered ip to young and lactating female rats was rapidly absorbed through the peritoneum and deposited in the urine, intestinal contents, and feces. Less than 0.5% of the radioactivity was expired as CO2 during the first 24 hr. Two yellow metabolites, accounting for 5 and 27% of the radioactivity in the urine, were found by paper chromatography. One metabolite retained the 2-amino-4-(5-nitro-2-furyl)thiazole moiety. Less than 0.5% of the radioactivity in the urine was due to unchanged 14-C-NFTA. The radioactivity level in the visceral organs reached a maximum 2 hr after dosing and then gradually decreased. Liver contained considerably more radioactivity than did other visceral organs; this was mainly distributed in the cytosol and 900g pellets. Fifty per cent of the radioactivity in the liver was bound to the hot trichloroacetic acid (TCA)-insoluble fraction; that bound to the cold TCA-insoluble fraction increased gradually from 66.9% at 2 hr to 82.6% at 24 hr. The radioactivity bound to the cold and hot TCA-insoluble fractions in kidney remained at 30% and 20%, respectively. Nitroreduction of 14-C-NFTA by microsomes, as a prerequisite of the binding of metabolite to microsomal protein, was demonstrated. Addition of L-cysteine or reduced glutathione to the incubation mixture did not alter the nitroreductase activity of the microsomes; however, binding of radioactivity to protein was significantly decreased. Addition of other amino acids did not significantly decrease the nitroreductase activity or binding to protein. These results suggest that reduced NFTA binds to the protein sulfhydryl groups. Since 14-C-NFTA binds to macromolecules in vivo,nitroreductionmay be important for the metabolism of 5-nitrofurans."}
{"id": "PMID:236165", "title": "Hydroxylation of 14-C-niflumic acid by phenobarbital-induced rat liver microsomes.", "content": "Hydroxylation of niflumic acid to 4'-hydroxyniflumic acid and 5-hydroxyniflumic acid by rat liver microsomes from untreated animals or phenobarbital-pretreated animals has been demonstrated. Pretreatment of rats with phenobarbital (50 mg/kg) increased the 4'-hydroxylase activity 53%, whreas the 5-hydroxylase activity was increased 205%. Niflumic acid inhibited of 4'- or 5-hydroxylase was observed with SKF 525-A. WIN 13099 inhibited both hydroxylases noncompetitvely. With freshly prepared microsomes, acetone, at concentrations frozen and aged microsomes, maximum enhancement of 4'-hydroxylase was obtained at 5% acetone; little or no effect on 5-hydroxylase was observed at the same concentration. At 10% acetone, the 4'- and 5-hydroxylases were inhibited 33 and 73% respectively. The data indicate that at least two different enzyme systems are involved in the hydroxylation of niflumic acid by the microsomes of rat liver.", "contents": "Hydroxylation of 14-C-niflumic acid by phenobarbital-induced rat liver microsomes. Hydroxylation of niflumic acid to 4'-hydroxyniflumic acid and 5-hydroxyniflumic acid by rat liver microsomes from untreated animals or phenobarbital-pretreated animals has been demonstrated. Pretreatment of rats with phenobarbital (50 mg/kg) increased the 4'-hydroxylase activity 53%, whreas the 5-hydroxylase activity was increased 205%. Niflumic acid inhibited of 4'- or 5-hydroxylase was observed with SKF 525-A. WIN 13099 inhibited both hydroxylases noncompetitvely. With freshly prepared microsomes, acetone, at concentrations frozen and aged microsomes, maximum enhancement of 4'-hydroxylase was obtained at 5% acetone; little or no effect on 5-hydroxylase was observed at the same concentration. At 10% acetone, the 4'- and 5-hydroxylases were inhibited 33 and 73% respectively. The data indicate that at least two different enzyme systems are involved in the hydroxylation of niflumic acid by the microsomes of rat liver."}
{"id": "PMID:236170", "title": "Adrenal hormones and increase of liver tyrosine aminotransferase and tryptophan pyrrolase activity after immobilization in rats.", "content": "In adrenomedullectomized rats the postimmobilization increase of liver tyrosine aminotransferase and tryptophan pyrrolase activity was similar as in intact animals, wherease in adrenalectomized rats this response was completely absent. In intact animals a positive correlation between the magnitude of the response of both enzymes and the duration of immobilization and/or the extent of plasma corticosterone increase was observedmit is concluded that the postimmobilization hyperactivity of both enzymes arises exclusively as a consequence of hypercorticosteronaemia, catecholamines and other hormones being without any influence on this response.", "contents": "Adrenal hormones and increase of liver tyrosine aminotransferase and tryptophan pyrrolase activity after immobilization in rats. In adrenomedullectomized rats the postimmobilization increase of liver tyrosine aminotransferase and tryptophan pyrrolase activity was similar as in intact animals, wherease in adrenalectomized rats this response was completely absent. In intact animals a positive correlation between the magnitude of the response of both enzymes and the duration of immobilization and/or the extent of plasma corticosterone increase was observedmit is concluded that the postimmobilization hyperactivity of both enzymes arises exclusively as a consequence of hypercorticosteronaemia, catecholamines and other hormones being without any influence on this response."}
{"id": "PMID:236171", "title": "LH-RH interactions with pituitary receptors: Properties and characterization.", "content": "The plasma membrane initiator system for actions of LH-RH was characterized. Binding of 125-I-LH-RH to the anterior pituitary plasma membrane was studied at 4 degrees C and at 37 degrees C. Two binding sites were indentified which possessed apparent affinity constants of 2 times 10- minus 8M and 2 times 10- minus 7M, respectively. The high affinity binding site was competible and saturable by TRH. These data suggest that the low affinity binding site is the physiological receptor for mediation of LH-RH stimulated LHrelease. LH-RH-receptor interaction has been shown to be a temperature and pH-dependent process. Less binding was observed at 37 degrees C than at 4 degrees C. Below pH 6 and above pH 8 a sharp drop in LH-RH binding to the cell membrane was recorded. Ca++, Mg++ and Mn++ were shown to inhibit the binding. Mn++ (16 mM) showed 50 percent inhibition of binding of LH-RH to the anterior pituitary plasma membrane fractions. On the other hand, increasing ionic strength enhanced LH-RH binding. The results of our study on the LH-RH-receptor systems offer a new approach to the study of LH-RH actions and facilitate the interpretation of earlier observations.", "contents": "LH-RH interactions with pituitary receptors: Properties and characterization. The plasma membrane initiator system for actions of LH-RH was characterized. Binding of 125-I-LH-RH to the anterior pituitary plasma membrane was studied at 4 degrees C and at 37 degrees C. Two binding sites were indentified which possessed apparent affinity constants of 2 times 10- minus 8M and 2 times 10- minus 7M, respectively. The high affinity binding site was competible and saturable by TRH. These data suggest that the low affinity binding site is the physiological receptor for mediation of LH-RH stimulated LHrelease. LH-RH-receptor interaction has been shown to be a temperature and pH-dependent process. Less binding was observed at 37 degrees C than at 4 degrees C. Below pH 6 and above pH 8 a sharp drop in LH-RH binding to the cell membrane was recorded. Ca++, Mg++ and Mn++ were shown to inhibit the binding. Mn++ (16 mM) showed 50 percent inhibition of binding of LH-RH to the anterior pituitary plasma membrane fractions. On the other hand, increasing ionic strength enhanced LH-RH binding. The results of our study on the LH-RH-receptor systems offer a new approach to the study of LH-RH actions and facilitate the interpretation of earlier observations."}
{"id": "PMID:236172", "title": "Calcitonin inhibition of bone cell metabolism in vivo: an experimental study in dogs.", "content": "Calcitonin (CT) has been shown to act by decreasing the output of calcium from the bone, but the precise mechanism that brings about this change is still not fully understood. The present investigation was designed to study the effect of CT on the metablic activity of bone cells, utilizing changes in oxygen consumption and carbon dioxide production as indices of tissue metabolism. Arterio-venous gradients of calcium, inorganic phosphate, hydroxyproline, oxygen, carbon dioxide and hydrogen ions were studied across the canine femur. The results showed that the hypocalcemic action of CT was accompanied by a corresponding decrease in free hydroxyproline output from the bone, demonstrating that decreased bone resorption was responsible for the fall in plasma calcium levels. Reduced oxygen consumption and decreased carbon dioxide production by the bone showed that CT acted by inhibiting the metabolic activity of bone cells in vivo. It is speculated that CT may have acted by depressing mitochondrial respiration.", "contents": "Calcitonin inhibition of bone cell metabolism in vivo: an experimental study in dogs. Calcitonin (CT) has been shown to act by decreasing the output of calcium from the bone, but the precise mechanism that brings about this change is still not fully understood. The present investigation was designed to study the effect of CT on the metablic activity of bone cells, utilizing changes in oxygen consumption and carbon dioxide production as indices of tissue metabolism. Arterio-venous gradients of calcium, inorganic phosphate, hydroxyproline, oxygen, carbon dioxide and hydrogen ions were studied across the canine femur. The results showed that the hypocalcemic action of CT was accompanied by a corresponding decrease in free hydroxyproline output from the bone, demonstrating that decreased bone resorption was responsible for the fall in plasma calcium levels. Reduced oxygen consumption and decreased carbon dioxide production by the bone showed that CT acted by inhibiting the metabolic activity of bone cells in vivo. It is speculated that CT may have acted by depressing mitochondrial respiration."}
{"id": "PMID:236173", "title": "Effect of acute metabolic acidosis on vasopressin-dependent cyclic AMP in rat kidney.", "content": "Acidic media have been reported to inhibit the hydro-osmotic effect of vasopressin in toad bladders, probably through inhibition of the cyclic AMP system. However, the mechanism of inhibition of the cyclic AMP system is controversial. Therefore, that inhibitory mechanism was further investigated in rat kidneys. The antidiuretic response to vasopression was significantly inhibited in animals with metabolic acidosis. The inhibition of the antidiuretic response was associated with a smaller than normal increase of urinary excretion of cyclic AMP after the iv injection of vasopressin. In in vitro experiments, both the increase of cyclic AMP concentration in renal medullary slices and the activation of adenylate cyclase in medulla by vasopressin were significantly less in acidic than in control media. These findings suggest that medabolic acidosis inhibits the antidiuretic effect of vasopressin by inhibiting the vasopressin-dependent cyclic AMP system in the kidney. Acidic media also inhibited cyclic AMP-phosphodiesterase. These dual effects of acidosis on adenylate cyclase and cyclic AMP-phosphodiesterase may explain the conflicting findings observed in the experiments on toad bladders.", "contents": "Effect of acute metabolic acidosis on vasopressin-dependent cyclic AMP in rat kidney. Acidic media have been reported to inhibit the hydro-osmotic effect of vasopressin in toad bladders, probably through inhibition of the cyclic AMP system. However, the mechanism of inhibition of the cyclic AMP system is controversial. Therefore, that inhibitory mechanism was further investigated in rat kidneys. The antidiuretic response to vasopression was significantly inhibited in animals with metabolic acidosis. The inhibition of the antidiuretic response was associated with a smaller than normal increase of urinary excretion of cyclic AMP after the iv injection of vasopressin. In in vitro experiments, both the increase of cyclic AMP concentration in renal medullary slices and the activation of adenylate cyclase in medulla by vasopressin were significantly less in acidic than in control media. These findings suggest that medabolic acidosis inhibits the antidiuretic effect of vasopressin by inhibiting the vasopressin-dependent cyclic AMP system in the kidney. Acidic media also inhibited cyclic AMP-phosphodiesterase. These dual effects of acidosis on adenylate cyclase and cyclic AMP-phosphodiesterase may explain the conflicting findings observed in the experiments on toad bladders."}
{"id": "PMID:236174", "title": "A 3'-deoxymononucleotide-producing nuclease from the marine sponge Verongia aerophoba. II. General properties.", "content": "The properties of a 3'-deoxymono-nucleotide-producing nuclease highly purified from the marine sponge Verongia aerophoba are described. The hydrolysis of heat-dentured DNA-proceeds at about five fold the rate of native, double-stranded DNA. The enzyme behaves as an exonuclease by producing 3'-deoxymononucleotides. Kinetic analysis by means of initial hyperchromicity at 260 nm indicates that the enzyme requries 120 mmol/l of mono-valent and 30 mmol/l of divalent cations with a clear dependence on ionic radius. The enzyme has  a pH optimum at 4.7, the pH value of the isoelectric point is 6.1. The molecular weight has been evaluated at 62,000.", "contents": "A 3'-deoxymononucleotide-producing nuclease from the marine sponge Verongia aerophoba. II. General properties. The properties of a 3'-deoxymono-nucleotide-producing nuclease highly purified from the marine sponge Verongia aerophoba are described. The hydrolysis of heat-dentured DNA-proceeds at about five fold the rate of native, double-stranded DNA. The enzyme behaves as an exonuclease by producing 3'-deoxymononucleotides. Kinetic analysis by means of initial hyperchromicity at 260 nm indicates that the enzyme requries 120 mmol/l of mono-valent and 30 mmol/l of divalent cations with a clear dependence on ionic radius. The enzyme has  a pH optimum at 4.7, the pH value of the isoelectric point is 6.1. The molecular weight has been evaluated at 62,000."}
{"id": "PMID:236175", "title": "Renal glutaminase in postnatal and adult rats.", "content": "Properties of renal phosphate-dependent glutaminase (EC 3.5.1.2), assayed in tissue homogenates, were compared in adult, 2-week-old, and newborn rats. Vmax, Km glutamine, pH optimum, inhibition by glutamate, activation by phosphate, intracellular distribution, and the possible presence of activators or inhibitors were examined. Although Vmax increased threefold during postnatal development, no major differences in the properties of the enzyme at the three stages of development were noted. It was concluded that the enzyme protein remains the same throughout development, both in biochemical properties and intracellular location, but that more of it is accumulated or is converted to an active state as the kidney matures.", "contents": "Renal glutaminase in postnatal and adult rats. Properties of renal phosphate-dependent glutaminase (EC 3.5.1.2), assayed in tissue homogenates, were compared in adult, 2-week-old, and newborn rats. Vmax, Km glutamine, pH optimum, inhibition by glutamate, activation by phosphate, intracellular distribution, and the possible presence of activators or inhibitors were examined. Although Vmax increased threefold during postnatal development, no major differences in the properties of the enzyme at the three stages of development were noted. It was concluded that the enzyme protein remains the same throughout development, both in biochemical properties and intracellular location, but that more of it is accumulated or is converted to an active state as the kidney matures."}
{"id": "PMID:236176", "title": "The serum activity of glucose-6phosphatase and 5'-nucleotidase during human pregnancy.", "content": "An attempt has been made to show that the increase in enzyme activities in sera of pregnant women found with glucose-6-phosphate and adenosine 5'-monophosphate as substrates (described as glucose-6-phosphatase and 5'-nucleotidase) was due to the increase in alkaline phosphatase. The three enzyme activities has pH optima and heat stability characteristics of alkaline phosphatase. The response to the action of inhibitors and activators was typical for alkaline phosphatase. There was an identical increase in all three enzyme activities during pregnancy. As a control similar investigations were made with liver and placental tissue extracts.", "contents": "The serum activity of glucose-6phosphatase and 5'-nucleotidase during human pregnancy. An attempt has been made to show that the increase in enzyme activities in sera of pregnant women found with glucose-6-phosphate and adenosine 5'-monophosphate as substrates (described as glucose-6-phosphatase and 5'-nucleotidase) was due to the increase in alkaline phosphatase. The three enzyme activities has pH optima and heat stability characteristics of alkaline phosphatase. The response to the action of inhibitors and activators was typical for alkaline phosphatase. There was an identical increase in all three enzyme activities during pregnancy. As a control similar investigations were made with liver and placental tissue extracts."}
{"id": "PMID:236177", "title": "Two forms of 4-aminobutyrate transaminase in guinea pig brain.", "content": "4-Aminobutyrate transaminase (GABA-T, 4-aminobutyrate alpha-oxoglutrate aminotransferase, EC 2.6.1.19) is an enzyme that inactivates the inhibitory neurotransmitter, GABA, but its pharmacological function is uncertain. Two forms of guiena pig brain GABA-T were isolated by DEAE-cellulose chromatography and designated as GABA-T-I and II, corresponding to an anionic and a cationic form. The enzymes were inhibited by high concentrations of a cationic form. The enzymes were inhibited by high concentrations of alpha-oxoglutrate (alpha-KG). Kinetic consists for GABA, when determined at pH 7.9 adn 1 mmol/l alpha-KG, were 0.74 mmol/l. GABA-T activity was inhibited by chloride and other anions. Kinetic analysis revealed chloride ion as a conpetitive inhibitor against GABA, but the Ki values differed among GABA-T-I and II (Ki equals 120 and 60 mmol/l, respectively). Similar  degrees of difference were observed with acetate and lactate ion. These results suggest that GABA-T-II may regulate the GABA level in the inhibitory neurons and may play a similar functional role as that exhibited by monoamine oxidase in other synapses.", "contents": "Two forms of 4-aminobutyrate transaminase in guinea pig brain. 4-Aminobutyrate transaminase (GABA-T, 4-aminobutyrate alpha-oxoglutrate aminotransferase, EC 2.6.1.19) is an enzyme that inactivates the inhibitory neurotransmitter, GABA, but its pharmacological function is uncertain. Two forms of guiena pig brain GABA-T were isolated by DEAE-cellulose chromatography and designated as GABA-T-I and II, corresponding to an anionic and a cationic form. The enzymes were inhibited by high concentrations of a cationic form. The enzymes were inhibited by high concentrations of alpha-oxoglutrate (alpha-KG). Kinetic consists for GABA, when determined at pH 7.9 adn 1 mmol/l alpha-KG, were 0.74 mmol/l. GABA-T activity was inhibited by chloride and other anions. Kinetic analysis revealed chloride ion as a conpetitive inhibitor against GABA, but the Ki values differed among GABA-T-I and II (Ki equals 120 and 60 mmol/l, respectively). Similar  degrees of difference were observed with acetate and lactate ion. These results suggest that GABA-T-II may regulate the GABA level in the inhibitory neurons and may play a similar functional role as that exhibited by monoamine oxidase in other synapses."}
{"id": "PMID:236179", "title": "Activities of tyrosine, alanine and aspartate aminotransferases of fetal rat liver in organ culture.", "content": "The levels of tyrosine, aspartate and alanine aminotransferases of fetal rat liver were measured and compared with values reported in the literature. Incubation of explants of fetal liver in organ culture resulted in spontaneous increases in tyrosine and alanine aminotransferases, and decrease in aspartate aminotransferase.", "contents": "Activities of tyrosine, alanine and aspartate aminotransferases of fetal rat liver in organ culture. The levels of tyrosine, aspartate and alanine aminotransferases of fetal rat liver were measured and compared with values reported in the literature. Incubation of explants of fetal liver in organ culture resulted in spontaneous increases in tyrosine and alanine aminotransferases, and decrease in aspartate aminotransferase."}
{"id": "PMID:236180", "title": "D-asparatate oxidase in the thyroid gland.", "content": "D-Aspartate oxidase was isolated from the pig thyroid gland and purified over 600 times. The enzyme was obtained in an inactive form of apoenzyme and was activated by FAD. It was specific towards the D-form of aspartic acid, had no effect on the L-form, and was also inactive towards other monocarboxlyic D-amino acids. The enzyme was only slightly active towards D-glutamate. The Michaelis constant based on the Lineaweaver-Burk plot was 5 mmol/l. The optimum pH was 8.7. D-Aspartate oxidase was inhibited by KCN in concentrations varying from 0.05 to 1 mmol/l. The biological role of this enzyme in the thyroid gland is discussed.", "contents": "D-asparatate oxidase in the thyroid gland. D-Aspartate oxidase was isolated from the pig thyroid gland and purified over 600 times. The enzyme was obtained in an inactive form of apoenzyme and was activated by FAD. It was specific towards the D-form of aspartic acid, had no effect on the L-form, and was also inactive towards other monocarboxlyic D-amino acids. The enzyme was only slightly active towards D-glutamate. The Michaelis constant based on the Lineaweaver-Burk plot was 5 mmol/l. The optimum pH was 8.7. D-Aspartate oxidase was inhibited by KCN in concentrations varying from 0.05 to 1 mmol/l. The biological role of this enzyme in the thyroid gland is discussed."}
{"id": "PMID:236181", "title": "Activation energy, relative substrate specificity and optimum pH of guanase from humanrat, mouse and guinea pig sera and tissues.", "content": "Some properties of serum and tissue guanase from man, rat, mouse and guinea pig have been studied. Serum guanase differs from tissue guanase in activation energy in the human species and in guinea pig. The mouse and rat brain enzyme differs from the liver and kidney enzyme. The guanase of each species differs from the enzyme of the other species in one or more properties.", "contents": "Activation energy, relative substrate specificity and optimum pH of guanase from humanrat, mouse and guinea pig sera and tissues. Some properties of serum and tissue guanase from man, rat, mouse and guinea pig have been studied. Serum guanase differs from tissue guanase in activation energy in the human species and in guinea pig. The mouse and rat brain enzyme differs from the liver and kidney enzyme. The guanase of each species differs from the enzyme of the other species in one or more properties."}
{"id": "PMID:236182", "title": "Effect of magnesium ion (Mg2+) and the magnesium adenosine triphosphate ion (MgATP2-) on pigeon liver pyruvate carboxylase.", "content": "Kinetic methods have been used to determine whether Mg2+ and MgATP2- play an important role in regulating pigeon liver pyruvate carboxylase [pyruvate: CO2 ligase (ADP), EC 6.4.1.1]. Mg2+ not only forms a complex with ATP4- (MgATP2-) but is also required for the enzyme activation (and probably for the binding of MgATP2- to this enzyme). Contrary to the results of other investigators, the MgATP2- complex was not found to activate pigeon liver pyruvate carboxylase. We could not demonstrate homotropic cooperativity with MgATP2-. Excess Mg2+ induced allosteric stimulation of the enzymatic activity at different concentrations of MgATP2-. With different Mg2+ concentrations, changes also occurred in the apparent Km, Vmax and Rs values. Without excess of Mg2+ (heterotropic effector) only about 2% of the total enzymic activity available could be demonstrated in the presence of MgATP2-. It is concluded that Mg2+ exhibits a homotropic cooperative effect and is required for the activation of this enzyme. Mg2+ may bind either to a specific effector site, at the active site, or at the binding site for MgATP2- which is capable of functioning as an effector site and in this way facilitates the carboxylation of pyruvate.", "contents": "Effect of magnesium ion (Mg2+) and the magnesium adenosine triphosphate ion (MgATP2-) on pigeon liver pyruvate carboxylase. Kinetic methods have been used to determine whether Mg2+ and MgATP2- play an important role in regulating pigeon liver pyruvate carboxylase [pyruvate: CO2 ligase (ADP), EC 6.4.1.1]. Mg2+ not only forms a complex with ATP4- (MgATP2-) but is also required for the enzyme activation (and probably for the binding of MgATP2- to this enzyme). Contrary to the results of other investigators, the MgATP2- complex was not found to activate pigeon liver pyruvate carboxylase. We could not demonstrate homotropic cooperativity with MgATP2-. Excess Mg2+ induced allosteric stimulation of the enzymatic activity at different concentrations of MgATP2-. With different Mg2+ concentrations, changes also occurred in the apparent Km, Vmax and Rs values. Without excess of Mg2+ (heterotropic effector) only about 2% of the total enzymic activity available could be demonstrated in the presence of MgATP2-. It is concluded that Mg2+ exhibits a homotropic cooperative effect and is required for the activation of this enzyme. Mg2+ may bind either to a specific effector site, at the active site, or at the binding site for MgATP2- which is capable of functioning as an effector site and in this way facilitates the carboxylation of pyruvate."}
{"id": "PMID:236183", "title": "Flavin-nicotinamide biscoenzymes: models for the interaction between NADH (NADPH) and flavin in flavoenzymes. Reaction rates and physicochemical properties of intermediate species.", "content": "1. Flavin-nicotinamide biscoenzymes covalently linked by two, three or four methylene groups through positions N(10) of the flavin (Fl) and (N1) of the nicontinamide (Nic) form long-wavelength-absorbing, intramolecular complexes when the flavin part of the molecule is reduced specifically. The energy of the long-wavelength transition is minimal and its intensity maximal for (see journal for formula). 2. The increasing proximity of the positively charged nicotinamide lowers the pK-value of dihydroflavin deprotonation up to 1.7 units and the flavin oxidation-reduction potential becomes more positive up to 116 mV. 3. Specific reduction of the nicotinamide part of the biscoenzymes yields transient, long-wavelength-absorbing complexes. The energy of the long-wavelength transition is minimal and its intensity maximal for the complex (see journal for formula). 4. The rate of intramolecular flavin-dependent dihydronicotinamide dehydrogenation is highest for (see journal for formula), about 3 times slower for (see journal for formula) and 100 times slower for (see journal for formula). 5. The results obtained in this study are consistent with a reaction mechanism that involves formation of a charge transfer complex between reduced nicotinamide and oxidized flavin and rate-limiting heterolytic breakdown into products.", "contents": "Flavin-nicotinamide biscoenzymes: models for the interaction between NADH (NADPH) and flavin in flavoenzymes. Reaction rates and physicochemical properties of intermediate species. 1. Flavin-nicotinamide biscoenzymes covalently linked by two, three or four methylene groups through positions N(10) of the flavin (Fl) and (N1) of the nicontinamide (Nic) form long-wavelength-absorbing, intramolecular complexes when the flavin part of the molecule is reduced specifically. The energy of the long-wavelength transition is minimal and its intensity maximal for (see journal for formula). 2. The increasing proximity of the positively charged nicotinamide lowers the pK-value of dihydroflavin deprotonation up to 1.7 units and the flavin oxidation-reduction potential becomes more positive up to 116 mV. 3. Specific reduction of the nicotinamide part of the biscoenzymes yields transient, long-wavelength-absorbing complexes. The energy of the long-wavelength transition is minimal and its intensity maximal for the complex (see journal for formula). 4. The rate of intramolecular flavin-dependent dihydronicotinamide dehydrogenation is highest for (see journal for formula), about 3 times slower for (see journal for formula) and 100 times slower for (see journal for formula). 5. The results obtained in this study are consistent with a reaction mechanism that involves formation of a charge transfer complex between reduced nicotinamide and oxidized flavin and rate-limiting heterolytic breakdown into products."}
{"id": "PMID:236184", "title": "Purification and kinetic properties of chalcone-flavanone isomerase from soya bean.", "content": "The chalcone-flavanone isomerase from soya bean seed has been purified 8300-fold. A molecular weight of 15,600 plus or minus 1000 has been determined for the enzyme. Effects of iodoacetamide and sodium tetrathionate on the enzyme, and pH dependence of the catalytic step, indicate that a sulphydryl group is not involved in the reaction mechanism and the catalytic group is probably an imidazole side chain in the basic form. The kinetics of the isomerisation of isoliquiritigenin to liquiritigenin have been examined and show that at pH 7.6 the reaction is reversible with an equilibrium constant of 37 in favour of flavanone. A number of flavonoid compounds competitively inhibit the reaction, suggesting a possible regulatory role for this enzyme in flavonoid biosynthesis.", "contents": "Purification and kinetic properties of chalcone-flavanone isomerase from soya bean. The chalcone-flavanone isomerase from soya bean seed has been purified 8300-fold. A molecular weight of 15,600 plus or minus 1000 has been determined for the enzyme. Effects of iodoacetamide and sodium tetrathionate on the enzyme, and pH dependence of the catalytic step, indicate that a sulphydryl group is not involved in the reaction mechanism and the catalytic group is probably an imidazole side chain in the basic form. The kinetics of the isomerisation of isoliquiritigenin to liquiritigenin have been examined and show that at pH 7.6 the reaction is reversible with an equilibrium constant of 37 in favour of flavanone. A number of flavonoid compounds competitively inhibit the reaction, suggesting a possible regulatory role for this enzyme in flavonoid biosynthesis."}
{"id": "PMID:236185", "title": "The threonine-sensitive homoserine dehydrogenase and aspartokinase activities of Escherichia coli K12. Specific inactivation of the homoserine dehydrogenase activity by the affinity label, 2-amino-4-oxo-5-chloropentanoic acid.", "content": "2-Amino-4-oxo-5-chloropentanoic acid inactivates specifically the homoserine dehydrogenase activity of the bifunctional enzyme, aspartokinase I--homoserine dehydrogenase I. The aspartokinase activity remains essentially untouched and retains its threonine sensitivity. The inactivation of the dehydrogenase requires the covalent binding of one equivalent of the analogue per subunit. Alkylation does not affect the tetrameric state of the protein. The alkylating agent, a substrate analogue, meets the qualitative and quantitative requirements of an affinity label.", "contents": "The threonine-sensitive homoserine dehydrogenase and aspartokinase activities of Escherichia coli K12. Specific inactivation of the homoserine dehydrogenase activity by the affinity label, 2-amino-4-oxo-5-chloropentanoic acid. 2-Amino-4-oxo-5-chloropentanoic acid inactivates specifically the homoserine dehydrogenase activity of the bifunctional enzyme, aspartokinase I--homoserine dehydrogenase I. The aspartokinase activity remains essentially untouched and retains its threonine sensitivity. The inactivation of the dehydrogenase requires the covalent binding of one equivalent of the analogue per subunit. Alkylation does not affect the tetrameric state of the protein. The alkylating agent, a substrate analogue, meets the qualitative and quantitative requirements of an affinity label."}
{"id": "PMID:236186", "title": "Evidence for an essential lysine in glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides.", "content": "1. Pyridoxal 5'-phosphate inhibits glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides reversibly which Ki equals 0.04-0.06 mM. 2. This inhibition is competitive with respect to glucose 6-phosphate and non-competitive with respect to NADP+ or NAD+. Interaction between enzyme and excess pyridoxal 5'-phosphate follows pseudo-first-order kinetics and indicates that one molecule of inhibitor reacts with each active unit of enzyme. 3. Substrate and coenzyme protect the enzyme from inhibition by pyridoxal 5'-phosphate. Dissociation constants for NADP+ and glucose 6-phosphate were determined from their effects on the kinetics of enzyme--inhibitor interaction. 4. Reaction of the enzyme with pyridoxal 5'-phosphate produces a typical Schiff-base absorbance peak at 430 nm. Subsequent reduction with sodium borohydride leads to spectral changes characteristic for the formation of a secondary amine. 5. The irreversibly inactivated enzyme thus produced contains two moles of inhibitor per mole of enzyme (two subunits per mole). After protein hydrolysis, N-6-pyridoxyllysine can be identified by paper chromatography. 6. The enzyme is inhibited irreversibly by 1-fluoro-2,4-dinitrobenzene, even in the presence of excess 2-mercaptoethanol. At least one dinitrophenyl group is bound per active unit of enzyme; 4 to 5 moles of dinitrophenyl group are bound per mole of enzyme. NADP+ AND GLUCOSE 6-PHOSPHATE PROTECT AGAINST INHIBITION BY 1-FLUORO-2,4-DINITROBENZENE. The absorption spectrum of dinitrophenyl-enzyme corresponds to that for dinitrophenylated amino groups. 7. These studies indicate that there is an essential lysine at the active site of the enzyme. It is suggested that the function of this lysine is to bind glucose 6-phosphate. 8. It is proposed that a group of \"active lysine\" proteins may exist (in analogy with the \"active serine\" enzymes), which share a common structural feature at their substrate-binding site and to which pyridoxal 5'-phosphate binds specifically.", "contents": "Evidence for an essential lysine in glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides. 1. Pyridoxal 5'-phosphate inhibits glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides reversibly which Ki equals 0.04-0.06 mM. 2. This inhibition is competitive with respect to glucose 6-phosphate and non-competitive with respect to NADP+ or NAD+. Interaction between enzyme and excess pyridoxal 5'-phosphate follows pseudo-first-order kinetics and indicates that one molecule of inhibitor reacts with each active unit of enzyme. 3. Substrate and coenzyme protect the enzyme from inhibition by pyridoxal 5'-phosphate. Dissociation constants for NADP+ and glucose 6-phosphate were determined from their effects on the kinetics of enzyme--inhibitor interaction. 4. Reaction of the enzyme with pyridoxal 5'-phosphate produces a typical Schiff-base absorbance peak at 430 nm. Subsequent reduction with sodium borohydride leads to spectral changes characteristic for the formation of a secondary amine. 5. The irreversibly inactivated enzyme thus produced contains two moles of inhibitor per mole of enzyme (two subunits per mole). After protein hydrolysis, N-6-pyridoxyllysine can be identified by paper chromatography. 6. The enzyme is inhibited irreversibly by 1-fluoro-2,4-dinitrobenzene, even in the presence of excess 2-mercaptoethanol. At least one dinitrophenyl group is bound per active unit of enzyme; 4 to 5 moles of dinitrophenyl group are bound per mole of enzyme. NADP+ AND GLUCOSE 6-PHOSPHATE PROTECT AGAINST INHIBITION BY 1-FLUORO-2,4-DINITROBENZENE. The absorption spectrum of dinitrophenyl-enzyme corresponds to that for dinitrophenylated amino groups. 7. These studies indicate that there is an essential lysine at the active site of the enzyme. It is suggested that the function of this lysine is to bind glucose 6-phosphate. 8. It is proposed that a group of \"active lysine\" proteins may exist (in analogy with the \"active serine\" enzymes), which share a common structural feature at their substrate-binding site and to which pyridoxal 5'-phosphate binds specifically."}
{"id": "PMID:236187", "title": "Fluorimetric study of conformational changes of various alpha-lactalbumins on agarose carriers.", "content": "1. Various insoluble alpha-lactalbumins (bovine, bovine glyco-alpha-lactalbumin, human and human nitrated) have been prepared by coupling these proteins on to an agarose gel with use of cyanogen bromide. 2. Some intrinsic fluorescence properties, such as fluorescence maximum and pH dependence, were considered in order to study conformational changes of the alpha-lactalbumins covalently bound to an insoluble matrix. Examination of the pH-fluorescence profiles as well as the position of the maximum in the emission spectrum indicates that the Sepharose matrix does not appreciably modify the conformation of human and bovine glyco-alpha-lactalbumins. Some changes in the fluorescence spectrum (peak shifting towards longer wavelength) was observed for bovine alpha-lactalbumin and appeared to be due to alteration of the environment of the tryptophan side-chains in the protein upon coupling to the agarose gel. The emission spectrum of the insolubilized human nitrated alpha-lactalbumin indicates that the polypeptide chain of this protein gained some native conformation when covalently bound to the carrier. 3. The extrinsic fluorescence of a bound dye, such as 2-p-toluidinylnaphthalene-6-sulfonate, was used to study and to compare the hydrophobic sites on the surface of insoluble alpha-lactalbumins with the same proteins in solution. Considering the fluorescence properties of the protein with dye complexes it was found that both states of alpha-lactalbumins (insoluble and free in solution) bind the dye with similar association constants. However, the positions of the maxima in the emission spectra are all somewhat shifted towards longer wavelengths, suggesting that the dye binding site is located in a more polar environment when the proteins are bound to agarose. The human nitrated alpha-lactalbumin retains about equal possibility of binding this fluorescent dye. 4. As shown for bovine alpha-lactalbumin in solution, the binding of 2-p-toluidinylnaphthalene-6-sulfonate towards the various insoluble alpha-lactalbumins was not appreciably modified by the presence of various small compounds such as sugars and UDP, which are effectors in the lactose synthetase function.", "contents": "Fluorimetric study of conformational changes of various alpha-lactalbumins on agarose carriers. 1. Various insoluble alpha-lactalbumins (bovine, bovine glyco-alpha-lactalbumin, human and human nitrated) have been prepared by coupling these proteins on to an agarose gel with use of cyanogen bromide. 2. Some intrinsic fluorescence properties, such as fluorescence maximum and pH dependence, were considered in order to study conformational changes of the alpha-lactalbumins covalently bound to an insoluble matrix. Examination of the pH-fluorescence profiles as well as the position of the maximum in the emission spectrum indicates that the Sepharose matrix does not appreciably modify the conformation of human and bovine glyco-alpha-lactalbumins. Some changes in the fluorescence spectrum (peak shifting towards longer wavelength) was observed for bovine alpha-lactalbumin and appeared to be due to alteration of the environment of the tryptophan side-chains in the protein upon coupling to the agarose gel. The emission spectrum of the insolubilized human nitrated alpha-lactalbumin indicates that the polypeptide chain of this protein gained some native conformation when covalently bound to the carrier. 3. The extrinsic fluorescence of a bound dye, such as 2-p-toluidinylnaphthalene-6-sulfonate, was used to study and to compare the hydrophobic sites on the surface of insoluble alpha-lactalbumins with the same proteins in solution. Considering the fluorescence properties of the protein with dye complexes it was found that both states of alpha-lactalbumins (insoluble and free in solution) bind the dye with similar association constants. However, the positions of the maxima in the emission spectra are all somewhat shifted towards longer wavelengths, suggesting that the dye binding site is located in a more polar environment when the proteins are bound to agarose. The human nitrated alpha-lactalbumin retains about equal possibility of binding this fluorescent dye. 4. As shown for bovine alpha-lactalbumin in solution, the binding of 2-p-toluidinylnaphthalene-6-sulfonate towards the various insoluble alpha-lactalbumins was not appreciably modified by the presence of various small compounds such as sugars and UDP, which are effectors in the lactose synthetase function."}
{"id": "PMID:236188", "title": "Dibenamine blockade on gastric acid secretion in vitro and its protection by histamine antagonists.", "content": "Experiments to protect the histamine receptor against dibenamine blockade were carried out to elucidate the pharmacological characteristics of the H2-histamine receptor system for gastric acid secretion in isolated bullfrog gastric mucosa. Dibenamine alone (5 times 10-minus 5 g/ml) irreversibly blocked both basal and histamine-stimulated acid secretion. However, when the preparation was treated with dibenamine in combination with histamine (1 times 10-minus 5 g/ml) irreversibly blocked both basal and histamine-stimulated acid secretion. However, when the preparation was treated with dibenamine in combination with histamine (1 times 10-minus 5 g/ml), the acid secretory response to histamine was restored after washing out dibenamine. Burimamide, an H2-receptor antagonist, also protected the histamine sensitivity against dibenamine blockade in the concentration of 1 times 10-minus 4 g/ml. Diphenhydramine and pyribenzamine were also protected with histamine receptor against dibenamine blockade. The acid secretion induced by the action of histamine on the diphenhydramine-protected receptor was antagonized by diphenhydramine as well as burimamide.", "contents": "Dibenamine blockade on gastric acid secretion in vitro and its protection by histamine antagonists. Experiments to protect the histamine receptor against dibenamine blockade were carried out to elucidate the pharmacological characteristics of the H2-histamine receptor system for gastric acid secretion in isolated bullfrog gastric mucosa. Dibenamine alone (5 times 10-minus 5 g/ml) irreversibly blocked both basal and histamine-stimulated acid secretion. However, when the preparation was treated with dibenamine in combination with histamine (1 times 10-minus 5 g/ml) irreversibly blocked both basal and histamine-stimulated acid secretion. However, when the preparation was treated with dibenamine in combination with histamine (1 times 10-minus 5 g/ml), the acid secretory response to histamine was restored after washing out dibenamine. Burimamide, an H2-receptor antagonist, also protected the histamine sensitivity against dibenamine blockade in the concentration of 1 times 10-minus 4 g/ml. Diphenhydramine and pyribenzamine were also protected with histamine receptor against dibenamine blockade. The acid secretion induced by the action of histamine on the diphenhydramine-protected receptor was antagonized by diphenhydramine as well as burimamide."}
{"id": "PMID:236189", "title": "The effects of arachidonic acid, indomethacin and SC-19220 on guinea-pig tracheal muscle tone.", "content": "The effects on guinea-pig tracheal muscle of a prostaglandin synthesis inhibitor, indomethacin, antagonist, SC-19220, and precursor, arachidonic acid have been studied in order to investigate the possible role of prostaglandins in the maintenance of respiratory smooth muscle tone. Indomethacin reduced the resting tone of the muscle, and increasing concentrations reduced the response to arachidonic acid without affecting the response to acetylcholine. Prostaglandins E2 and F2alpha caused contractions of indomethacin-relaxed muxcle, and tachyphylaxis was induced by repeated exposure of the muscle to these agonists, but not to arachidonic acid. The prostaglandin antagonist, SC-19220 relaxed the muscle and abolished its response to a standard dose of prostaglandin E2. Increasing concentrations of SC-19220 reduced the responses to both arachidonic acid and large doses of prostaglandin E2. The responses of tracheal muscle to arachidonic acid are concluded to be partly due to prostaglandin synthesis, supporting the hypothesis that this process maintanins tracheal muscle tone.", "contents": "The effects of arachidonic acid, indomethacin and SC-19220 on guinea-pig tracheal muscle tone. The effects on guinea-pig tracheal muscle of a prostaglandin synthesis inhibitor, indomethacin, antagonist, SC-19220, and precursor, arachidonic acid have been studied in order to investigate the possible role of prostaglandins in the maintenance of respiratory smooth muscle tone. Indomethacin reduced the resting tone of the muscle, and increasing concentrations reduced the response to arachidonic acid without affecting the response to acetylcholine. Prostaglandins E2 and F2alpha caused contractions of indomethacin-relaxed muxcle, and tachyphylaxis was induced by repeated exposure of the muscle to these agonists, but not to arachidonic acid. The prostaglandin antagonist, SC-19220 relaxed the muscle and abolished its response to a standard dose of prostaglandin E2. Increasing concentrations of SC-19220 reduced the responses to both arachidonic acid and large doses of prostaglandin E2. The responses of tracheal muscle to arachidonic acid are concluded to be partly due to prostaglandin synthesis, supporting the hypothesis that this process maintanins tracheal muscle tone."}
{"id": "PMID:236190", "title": "Neurotransmitter control of thyrotropin secretion in the rat.", "content": "In rats adapted to a +30 degrees C temperature for one week, transfer to a temperature of +4 degrees C increased immunoassay-able serum TSH from 150-300 ng/ml to 800-2000 ng/ml in 30 min. Since this response, as well as the level of serum TSH without stimulation, were decreased by reserpine, phentolamine, phenoxybenzamine, disulfiram and diethyldithiocarbamate, noradrenaline may be involved in the stimulation of TSH secretion. TRH-induced TSH increased was not blocked by reserpine. 1-Dopa, a noradrenaline precursor, decreased the TSH response to cold; alpha-methyl-p-tyrosine increased the TSH level. Apomorphine decreased the level of serum TSH and inhibited the response to cold. The possibility of a dopaminergic inhibitory factor released from the hypothalamus is discussed. 5-HT has possibly a role in the regulation of TSH secretion, since its precursor 5-HTP decreased the response to cold. No indication was found that acetylcholine is involved.", "contents": "Neurotransmitter control of thyrotropin secretion in the rat. In rats adapted to a +30 degrees C temperature for one week, transfer to a temperature of +4 degrees C increased immunoassay-able serum TSH from 150-300 ng/ml to 800-2000 ng/ml in 30 min. Since this response, as well as the level of serum TSH without stimulation, were decreased by reserpine, phentolamine, phenoxybenzamine, disulfiram and diethyldithiocarbamate, noradrenaline may be involved in the stimulation of TSH secretion. TRH-induced TSH increased was not blocked by reserpine. 1-Dopa, a noradrenaline precursor, decreased the TSH response to cold; alpha-methyl-p-tyrosine increased the TSH level. Apomorphine decreased the level of serum TSH and inhibited the response to cold. The possibility of a dopaminergic inhibitory factor released from the hypothalamus is discussed. 5-HT has possibly a role in the regulation of TSH secretion, since its precursor 5-HTP decreased the response to cold. No indication was found that acetylcholine is involved."}
{"id": "PMID:236191", "title": "Studies on the interaction of isoproterenol with plasma membranes isolated from rat myometrium.", "content": "Catecholamine stimulation of adenyl cyclase in plasma membranes from rat myometrium was typical of beta-adrenoceptor stimulation. Thus, isoproterenol was the most potent followed by epinephrine and norepinephrine; phenylephrine, a pure alpha-agonist, did not activate the enzyme. The catecholamine-induced activation was potently inhibited by propranolol, whereas phenozybenzamine was without effect. The ED50 for 1-isoproterenol activation was 10- minus 7 M. Binding of [3H]-d-isoproterenol to the same preparations bore little resemblance to the pattern of 1-isoproterenol activation of adenyl cyclase. Propranolol, even at high concentrations, was without significant effect. The degree of binding was inversely rflated to the osmolarity suggesting that diffusion may have contributed to the binding. This contention was further supported by the time course of binding which was biphasic- the first component (smaller than 4 min) being less affected by osmolarity than the second (greater than 4 min). The optimum pH for binding was 7.4.", "contents": "Studies on the interaction of isoproterenol with plasma membranes isolated from rat myometrium. Catecholamine stimulation of adenyl cyclase in plasma membranes from rat myometrium was typical of beta-adrenoceptor stimulation. Thus, isoproterenol was the most potent followed by epinephrine and norepinephrine; phenylephrine, a pure alpha-agonist, did not activate the enzyme. The catecholamine-induced activation was potently inhibited by propranolol, whereas phenozybenzamine was without effect. The ED50 for 1-isoproterenol activation was 10- minus 7 M. Binding of [3H]-d-isoproterenol to the same preparations bore little resemblance to the pattern of 1-isoproterenol activation of adenyl cyclase. Propranolol, even at high concentrations, was without significant effect. The degree of binding was inversely rflated to the osmolarity suggesting that diffusion may have contributed to the binding. This contention was further supported by the time course of binding which was biphasic- the first component (smaller than 4 min) being less affected by osmolarity than the second (greater than 4 min). The optimum pH for binding was 7.4."}
{"id": "PMID:236192", "title": "Pharmacological characterization of cardiac histamine receptors: sensitivity to H1-and H2-receptor agonists and antagonists.", "content": "In the isolated guinea pig heart, histamine H1-receptor antagonists inhibit the histamine-induced negative dromotropic effect, but not the positive inotropic and chronotropic effects (Levi and Kuye, 1974, European J. Pharmacol. 27, 330). Burimamide, the H2-receptor antagonist, inhibits the positive chronotropic effect of histamine (Black et al., 1972, Nature 236, 385). In this study, the hypothesis that H1- and H2-receptors selectively mediate the various cardiac effects of histamine was tested: (a) by investigating the inhibition of cardiac histamine effects by burimamide; (b) by studying the cardiac effects of 2-methylhistamine (an H1-agonist) and 4-methylhistamine (an H2-agonist). Burimamide, as a function of concentration, inhibited the positive inotropic and chronotropic effects of histamine, whereas it attenuated the negative dromotropic effect of histamine at the higher concentration only. 4-Methylhistamine caused dose-dependent positive inotropic and chronotropic but not negative dromotropic effects; conversely, with 2-methylhistamine the negative dromotropic effect prevailed. Sinus tachycardia and slowing of atrioventricular conduction were also obtained in the guinea pig in vivo by the i.v. administration of histamine. Burimamide selectively antagonized the positive chronotropic effect, whereas promethazine (an H1-antagonist) selectively inhibited the negative dromotropic effect. These results substantiate the hypothesis that H2-receptors mediate the histamine-induced increase in rate and contractility, whereas H1-receptors mediate the slowing of atrioventricular conduction.", "contents": "Pharmacological characterization of cardiac histamine receptors: sensitivity to H1-and H2-receptor agonists and antagonists. In the isolated guinea pig heart, histamine H1-receptor antagonists inhibit the histamine-induced negative dromotropic effect, but not the positive inotropic and chronotropic effects (Levi and Kuye, 1974, European J. Pharmacol. 27, 330). Burimamide, the H2-receptor antagonist, inhibits the positive chronotropic effect of histamine (Black et al., 1972, Nature 236, 385). In this study, the hypothesis that H1- and H2-receptors selectively mediate the various cardiac effects of histamine was tested: (a) by investigating the inhibition of cardiac histamine effects by burimamide; (b) by studying the cardiac effects of 2-methylhistamine (an H1-agonist) and 4-methylhistamine (an H2-agonist). Burimamide, as a function of concentration, inhibited the positive inotropic and chronotropic effects of histamine, whereas it attenuated the negative dromotropic effect of histamine at the higher concentration only. 4-Methylhistamine caused dose-dependent positive inotropic and chronotropic but not negative dromotropic effects; conversely, with 2-methylhistamine the negative dromotropic effect prevailed. Sinus tachycardia and slowing of atrioventricular conduction were also obtained in the guinea pig in vivo by the i.v. administration of histamine. Burimamide selectively antagonized the positive chronotropic effect, whereas promethazine (an H1-antagonist) selectively inhibited the negative dromotropic effect. These results substantiate the hypothesis that H2-receptors mediate the histamine-induced increase in rate and contractility, whereas H1-receptors mediate the slowing of atrioventricular conduction."}
{"id": "PMID:236193", "title": "Effect of antipsychotic drugs on homovanillic acid levels in striatum and olfactory tubercle of the rat.", "content": "Dose-response curves for the elevation of homovanillic acid levels in corpus striatum and olfactory tubercle of rats were determined by mass fragmentography after treatment with antipsychotic drugs. The older of potency in both regions was: haloperidol greater than chlorpromazine greater than thioridazine and clozapine. The relative elevation of the content of homovanillic acid was significantly greater in the striatum than in the olfactory tubercle for all drugs except thioridazine. The antipsychotic effect of the drugs tested may be related to the interference with dopaminergic mechanisms in striatal and/or limbic areas.", "contents": "Effect of antipsychotic drugs on homovanillic acid levels in striatum and olfactory tubercle of the rat. Dose-response curves for the elevation of homovanillic acid levels in corpus striatum and olfactory tubercle of rats were determined by mass fragmentography after treatment with antipsychotic drugs. The older of potency in both regions was: haloperidol greater than chlorpromazine greater than thioridazine and clozapine. The relative elevation of the content of homovanillic acid was significantly greater in the striatum than in the olfactory tubercle for all drugs except thioridazine. The antipsychotic effect of the drugs tested may be related to the interference with dopaminergic mechanisms in striatal and/or limbic areas."}
{"id": "PMID:236194", "title": "Influence of the adrenal gland on the pressor effect and antagonistic potency of angiotensin II analogs.", "content": "In ganglion blocked vagotomized rats, several 1,8-substituted angiotensin II analogs (250 ng/kg/min, i.v.) antagonized the pressor effect of angiotensin II. Dose ratios measured at the ED20 levels were: [Sar1,Ile8]-28; [Gac1,Ile8]- 19;[MeAla1,Ile8i1- 16;[MeIle1,Ile8]- 10;[sar1,Ala8]- 9;[me2Gly1,Ile8]- 4. Elimination of aspajtic acid in position 1 of [Ile8]-angiotensin II significantly reduced the antagonistic potency of the analog. No antagonistic effect was observed with [Phe4,Ile8] and [Ala4,Ile8]-angiotensin II even when infused at 6 mug/kg/min. During infusion, a partial rise in blood pressure was observed with all the above 1,8-substituted angiotensin II analogs. Phentolamine (100 mug/rat) injected 30 min after the start of the analog infusion reduced and sometimes abolished the pressor effect. However, phenoxybenzamine )Pbz, 2 mg/kg) injected 30 min prior to the analog infusion diminished but did not completely abolish the initial pressor effect. In adrenalectomized rats, the pressor effect was reduced by approximately 50 percent and disappeared completely 15-30 min after start of the infusion. Under these conditions, dose ratios of [Sar1,Ile8]-,[MeAla1,Ile8]- and [Gac1,Ile8]-angiotensin II were significantly reduced. Noradrenaline, 83 ng/kg/min. increased the ED20 value of angiotensin II(ratio 1.79) in normal rats but did not do so in adrenalectomized rats. In these rats no regular correlation was found between the angiotensin II ED20 values and initial blood pressure. These data indicate that under the present experimental conditions, the low pressor effect observed with these angiotensin II antagonists appears to be due to both adrenal catecholamine release and a direct vasoconstrictor effect. Variations in antagonistic activity of angiotensin II analogs, apart from changes introduced in the molecule, may be the manifestation of a complex interaction between angiotensin II, its antagonists, and the sympathoadrenal system.", "contents": "Influence of the adrenal gland on the pressor effect and antagonistic potency of angiotensin II analogs. In ganglion blocked vagotomized rats, several 1,8-substituted angiotensin II analogs (250 ng/kg/min, i.v.) antagonized the pressor effect of angiotensin II. Dose ratios measured at the ED20 levels were: [Sar1,Ile8]-28; [Gac1,Ile8]- 19;[MeAla1,Ile8i1- 16;[MeIle1,Ile8]- 10;[sar1,Ala8]- 9;[me2Gly1,Ile8]- 4. Elimination of aspajtic acid in position 1 of [Ile8]-angiotensin II significantly reduced the antagonistic potency of the analog. No antagonistic effect was observed with [Phe4,Ile8] and [Ala4,Ile8]-angiotensin II even when infused at 6 mug/kg/min. During infusion, a partial rise in blood pressure was observed with all the above 1,8-substituted angiotensin II analogs. Phentolamine (100 mug/rat) injected 30 min after the start of the analog infusion reduced and sometimes abolished the pressor effect. However, phenoxybenzamine )Pbz, 2 mg/kg) injected 30 min prior to the analog infusion diminished but did not completely abolish the initial pressor effect. In adrenalectomized rats, the pressor effect was reduced by approximately 50 percent and disappeared completely 15-30 min after start of the infusion. Under these conditions, dose ratios of [Sar1,Ile8]-,[MeAla1,Ile8]- and [Gac1,Ile8]-angiotensin II were significantly reduced. Noradrenaline, 83 ng/kg/min. increased the ED20 value of angiotensin II(ratio 1.79) in normal rats but did not do so in adrenalectomized rats. In these rats no regular correlation was found between the angiotensin II ED20 values and initial blood pressure. These data indicate that under the present experimental conditions, the low pressor effect observed with these angiotensin II antagonists appears to be due to both adrenal catecholamine release and a direct vasoconstrictor effect. Variations in antagonistic activity of angiotensin II analogs, apart from changes introduced in the molecule, may be the manifestation of a complex interaction between angiotensin II, its antagonists, and the sympathoadrenal system."}
{"id": "PMID:236195", "title": "Effects of hexamethonium and other ganglionic blocking agents on electrical activity of the esophagus induced by vagal stimulation in the dog.", "content": "Electrical activity of the dog's esophagus was evoked by electrical stimulation of the vagus nerve and recorded by using a suction electrode placed on the serosal surface of the esophagus. Neuromuscular blocking agents (d-tubocurarine and succinylcholine) blocked this activity, while atropine had no effect. Hexamethonium (in doses which did not effect neuromuscular transmission in the diaphragm) and high doses of nicotine significantly depressed the evoked esophageal electrical activity, while lower doses of nicotine facilitated the response. The results suggest that a certain proportion of the striated muscle of the esophagus is innervated by processes from the intermediate ganglion cells in the Auerbach plexus.", "contents": "Effects of hexamethonium and other ganglionic blocking agents on electrical activity of the esophagus induced by vagal stimulation in the dog. Electrical activity of the dog's esophagus was evoked by electrical stimulation of the vagus nerve and recorded by using a suction electrode placed on the serosal surface of the esophagus. Neuromuscular blocking agents (d-tubocurarine and succinylcholine) blocked this activity, while atropine had no effect. Hexamethonium (in doses which did not effect neuromuscular transmission in the diaphragm) and high doses of nicotine significantly depressed the evoked esophageal electrical activity, while lower doses of nicotine facilitated the response. The results suggest that a certain proportion of the striated muscle of the esophagus is innervated by processes from the intermediate ganglion cells in the Auerbach plexus."}
{"id": "PMID:236198", "title": "[A receptor for UDP-glucose in the microsomal membranes of rat hepatocytes].", "content": "Rat liver microsomal membranes have been shown to contain a biosynthetic pathway of UDP-glucose. In addition, they are able to bind UDP-glucose in a reversible manner, As UDP-glucose is also metabolized in these membranes, the study of the binding has been performed with a microsomal Triton X 100 extract. This reversible binding depends on pH (maximum at pH 8.1) and manganous ions, and disappears at pH 6.5. It exhibits a high affinity (K-diss equals 3 mu M), and a narrow specifity for UDP-glucose. Proteolytic digestion inhibits the binding up to 90%, showing that the UDP-glucose receptor has a proteic nature. These binding characteristics have been also found in the membranes themselves, indicating that the detergent solubilization does not destroy the protein binding capacity.", "contents": "[A receptor for UDP-glucose in the microsomal membranes of rat hepatocytes]. Rat liver microsomal membranes have been shown to contain a biosynthetic pathway of UDP-glucose. In addition, they are able to bind UDP-glucose in a reversible manner, As UDP-glucose is also metabolized in these membranes, the study of the binding has been performed with a microsomal Triton X 100 extract. This reversible binding depends on pH (maximum at pH 8.1) and manganous ions, and disappears at pH 6.5. It exhibits a high affinity (K-diss equals 3 mu M), and a narrow specifity for UDP-glucose. Proteolytic digestion inhibits the binding up to 90%, showing that the UDP-glucose receptor has a proteic nature. These binding characteristics have been also found in the membranes themselves, indicating that the detergent solubilization does not destroy the protein binding capacity."}
{"id": "PMID:236208", "title": "Problems and progress towards vaccination against bacterial infections of the respiratory tract.", "content": "A large number of bacterial species are causative agents of respiratory tract disease. The discussion will center on three infections selected because they represent different problems in control on the basis of epidemiologic and immunochemical factors. Group A hemolytic streptococci are common upper respiratory tract pathogens which may initiate severe non-suppurative sequelae such as rheumatic fever and glomerulonephritis. Recent progress concerning M protein vaccines will be reviewed. Pneumococci are still the most frequent cause of pneumonia at all ages. Pneumococcal vaccines are the prototype for purified polysaccharide vaccines since their effectiveness was demonstrated 30 years ago. The major problem in vaccination is the very large number of capsular serotypes. Pseudomonas aeruginosa represents the relatively new problem of gram-negative bacterial infections in the immunodepressed host. Demonstration of seven immunotypes as the cause of 90% of human infections has led to preparation of a multivalent vaccine composed of lipopolysaccharide antigens. Current knowledge of this vaccine will be discussed.", "contents": "Problems and progress towards vaccination against bacterial infections of the respiratory tract. A large number of bacterial species are causative agents of respiratory tract disease. The discussion will center on three infections selected because they represent different problems in control on the basis of epidemiologic and immunochemical factors. Group A hemolytic streptococci are common upper respiratory tract pathogens which may initiate severe non-suppurative sequelae such as rheumatic fever and glomerulonephritis. Recent progress concerning M protein vaccines will be reviewed. Pneumococci are still the most frequent cause of pneumonia at all ages. Pneumococcal vaccines are the prototype for purified polysaccharide vaccines since their effectiveness was demonstrated 30 years ago. The major problem in vaccination is the very large number of capsular serotypes. Pseudomonas aeruginosa represents the relatively new problem of gram-negative bacterial infections in the immunodepressed host. Demonstration of seven immunotypes as the cause of 90% of human infections has led to preparation of a multivalent vaccine composed of lipopolysaccharide antigens. Current knowledge of this vaccine will be discussed."}
{"id": "PMID:236209", "title": "Effect to gastric alkalinization on lower esophageal sphincter pressure and serum gastrin.", "content": "The purpose of this study was to measure the effect of alkaline intragastric pH on lower esophageal sphincter pressure (LESP) and on serum gastrin concentration in man. One hundred ten milliliters each of 0.1 N NaHCO3 and control solution were instilled into the stomach for 30 min in random order. Neither LESP nor serum gastrin were higher during the alkali instillation than during the control instillation. Individual subject's peak gastrin and peak LESP during the alkali period were not significantly higher than the corresponding basal values. We conclude that intragastric alkalinization did not increase total radioimmunoassayable serum gastrin concentration or LESP.", "contents": "Effect to gastric alkalinization on lower esophageal sphincter pressure and serum gastrin. The purpose of this study was to measure the effect of alkaline intragastric pH on lower esophageal sphincter pressure (LESP) and on serum gastrin concentration in man. One hundred ten milliliters each of 0.1 N NaHCO3 and control solution were instilled into the stomach for 30 min in random order. Neither LESP nor serum gastrin were higher during the alkali instillation than during the control instillation. Individual subject's peak gastrin and peak LESP during the alkali period were not significantly higher than the corresponding basal values. We conclude that intragastric alkalinization did not increase total radioimmunoassayable serum gastrin concentration or LESP."}
{"id": "PMID:236210", "title": "Interaction of calcium and magnesium on gastric acid secretion and serum gastrin concentration in man.", "content": "The effect of magnesium on calcium- and pentagastrin-induced gastric acid secretion and on calcium-induced gastrin secretion were studied in healthy volunteers. Intravenous infusion of calcium gluconate increased serum gastrin concentration as well as gastric volume secretion, acidity, and acid output. Addition of magnesium sulfate to the infusion caused a slight but insignificant increase in serum gastrin concentration, whereas volume secretion, acidity, and acid output were significantly depressed. Intravenous infusion of magnesium sulfate had no effect on gastric acid secretion induced by a submaximal pentagastrin infusion. The results indicate that magnesium antagonizes the activation of gastric acid secretion by calcium without suppressing gastrin release and may suggest that magnesium does not change the sensitivity of the parietal cell to gastrin.", "contents": "Interaction of calcium and magnesium on gastric acid secretion and serum gastrin concentration in man. The effect of magnesium on calcium- and pentagastrin-induced gastric acid secretion and on calcium-induced gastrin secretion were studied in healthy volunteers. Intravenous infusion of calcium gluconate increased serum gastrin concentration as well as gastric volume secretion, acidity, and acid output. Addition of magnesium sulfate to the infusion caused a slight but insignificant increase in serum gastrin concentration, whereas volume secretion, acidity, and acid output were significantly depressed. Intravenous infusion of magnesium sulfate had no effect on gastric acid secretion induced by a submaximal pentagastrin infusion. The results indicate that magnesium antagonizes the activation of gastric acid secretion by calcium without suppressing gastrin release and may suggest that magnesium does not change the sensitivity of the parietal cell to gastrin."}
{"id": "PMID:236211", "title": "Cardioversion 1975: foremost therapy for tachyarrhythmias.", "content": "Extensive clinical experience indicates that cardioversion is the most effective method now available for terminating cardiac tachyarrhythmias. This procedure is not accompanied by depression of myocardial contractility, conductivity, or excitability, a common sequel to the use of antiarrhythmic drugs. Furthermore, the incidence of complications with cardioversion is low. These features of effectiveness, safety, and simplicity permit cardioversion to be used by the noncardiologist physician, who may be less experienced than a cardiologist in recognizing arrrhythmias. Cardioversion has not reduced the need for antiarrhythmic agents; on the contrary, more such drugs are required to maintain normal sinus rhythm. The problem at present is not the terminating a tachyarrhythmia but in preventing its recurrence.", "contents": "Cardioversion 1975: foremost therapy for tachyarrhythmias. Extensive clinical experience indicates that cardioversion is the most effective method now available for terminating cardiac tachyarrhythmias. This procedure is not accompanied by depression of myocardial contractility, conductivity, or excitability, a common sequel to the use of antiarrhythmic drugs. Furthermore, the incidence of complications with cardioversion is low. These features of effectiveness, safety, and simplicity permit cardioversion to be used by the noncardiologist physician, who may be less experienced than a cardiologist in recognizing arrrhythmias. Cardioversion has not reduced the need for antiarrhythmic agents; on the contrary, more such drugs are required to maintain normal sinus rhythm. The problem at present is not the terminating a tachyarrhythmia but in preventing its recurrence."}
{"id": "PMID:236212", "title": "Mechanisms of lipid loss from the small intestinal mucosa.", "content": "Many water-soluble compounds have been shown to pass from the small intestinal mucosa into the lumen. In this work, the loss of lipids from the mucosa was investigated by perfusion experiments in rats, using 0-15M NaCl or buffer solutions over range of pH, with or without the addition of 5-7 or 11-4mM taurocholic acid. Perfusates were extracted for the estimation of individual lipids and for DNA, which is a measure of cell loss. The results suggest that free fatty acids reach the lumen by diffusion and that their solubility in the luminal fluid is a factor determining their rate of loss. Triglycerides, cholesterol, phosphatidyl ethanolamine, and phosphatidly choline are present onlyas  the result of desquamation of mucosal cells.", "contents": "Mechanisms of lipid loss from the small intestinal mucosa. Many water-soluble compounds have been shown to pass from the small intestinal mucosa into the lumen. In this work, the loss of lipids from the mucosa was investigated by perfusion experiments in rats, using 0-15M NaCl or buffer solutions over range of pH, with or without the addition of 5-7 or 11-4mM taurocholic acid. Perfusates were extracted for the estimation of individual lipids and for DNA, which is a measure of cell loss. The results suggest that free fatty acids reach the lumen by diffusion and that their solubility in the luminal fluid is a factor determining their rate of loss. Triglycerides, cholesterol, phosphatidyl ethanolamine, and phosphatidly choline are present onlyas  the result of desquamation of mucosal cells."}
{"id": "PMID:236257", "title": "Prolonged C3 depletion by cobra venom factor in thymus-deprived mice and its implication for the role of C3 as an essential second signal for B-cell triggering.", "content": "Cobra venom factor (CoF) is a potent immunogen in intact mice, and its capacity to deplete C3 is neutralized by antibody. In thymus-deprived (T times B) mice antibody was not elicited; C3 depletion by CoF was prolonged, and subsequent injections were also effective. The effect of prolonged C3 depletion was examined on the antibody response to two T cell-independent immunogens, levan and SIII. The spleen PFC responses to levan were unaffected by C3 depletion or thymus deprivation; those to SIII were unaffected by thymus deprivation but were diminished (not abolished) by C3 depletion. It is argued that the capacity to activate C3 is neither sufficient nor necessary to cause an immunogen to be T cell-independent.", "contents": "Prolonged C3 depletion by cobra venom factor in thymus-deprived mice and its implication for the role of C3 as an essential second signal for B-cell triggering. Cobra venom factor (CoF) is a potent immunogen in intact mice, and its capacity to deplete C3 is neutralized by antibody. In thymus-deprived (T times B) mice antibody was not elicited; C3 depletion by CoF was prolonged, and subsequent injections were also effective. The effect of prolonged C3 depletion was examined on the antibody response to two T cell-independent immunogens, levan and SIII. The spleen PFC responses to levan were unaffected by C3 depletion or thymus deprivation; those to SIII were unaffected by thymus deprivation but were diminished (not abolished) by C3 depletion. It is argued that the capacity to activate C3 is neither sufficient nor necessary to cause an immunogen to be T cell-independent."}
{"id": "PMID:236258", "title": "Defects in cell-mediated immunity during growth of a syngeneic simian virus-induced tumor.", "content": "Four assays of tumor-specific cell-mediated immunity were compared during growth of a syngeneic Simian-virus-40-induced tumor, mKSA. Major differences were found in immunity detected by the tumor neutralization test (the Winn test), direct tumor challenge, the microcytotoxicity assay and the -51chromium-release lymphocytotoxicity assay. Progressive growth of the neoplasm followed by loss of immunity (the eclipse phenomenon) was documented with the Winn test. It was established that this eclipse phenomenon represented a lesion in the T-cell system of tumor-bearing hosts. This lesion was found to be specific and unrelated to anatomic tumor location. The ability to produce graft-versus-host reactions, and the ability to respond to mitogens, were found to be generally intact in tumor-bearing animals. Cells capable of recognizing mKSA tumor antigens and reconstituting an immune response following surgical removal of tumor or upon transfer to normal mice were found in the spleens of mice bearing advanced tumors. No suppressor cells that might account for the eclipse phenomenon could be demonstrated. Tumor-bearer serum did not block neutralizing activity of immune spleen cells in the Winn test, and immune cells were capable of neutralizing tumor even in tumor-bearing hosts. The possibility that the lesion is intrinsic to T-cell precursors of effector cells is discussed.", "contents": "Defects in cell-mediated immunity during growth of a syngeneic simian virus-induced tumor. Four assays of tumor-specific cell-mediated immunity were compared during growth of a syngeneic Simian-virus-40-induced tumor, mKSA. Major differences were found in immunity detected by the tumor neutralization test (the Winn test), direct tumor challenge, the microcytotoxicity assay and the -51chromium-release lymphocytotoxicity assay. Progressive growth of the neoplasm followed by loss of immunity (the eclipse phenomenon) was documented with the Winn test. It was established that this eclipse phenomenon represented a lesion in the T-cell system of tumor-bearing hosts. This lesion was found to be specific and unrelated to anatomic tumor location. The ability to produce graft-versus-host reactions, and the ability to respond to mitogens, were found to be generally intact in tumor-bearing animals. Cells capable of recognizing mKSA tumor antigens and reconstituting an immune response following surgical removal of tumor or upon transfer to normal mice were found in the spleens of mice bearing advanced tumors. No suppressor cells that might account for the eclipse phenomenon could be demonstrated. Tumor-bearer serum did not block neutralizing activity of immune spleen cells in the Winn test, and immune cells were capable of neutralizing tumor even in tumor-bearing hosts. The possibility that the lesion is intrinsic to T-cell precursors of effector cells is discussed."}
{"id": "PMID:236269", "title": "Acid hydrolases in the suckling rat small intestine. II. On the importance of alkaline phosphatase inhibition in the histochemical localization of acid phosphatase activity.", "content": "Phosphatase activities against beta-glycerophosphate, I-naphthyl phosphate and naphthol AS-TR phosphate were investigated, at acid and aldaline pH levels, using unfixed and fixed cryostat sections of suckling rat jejunum. The use of 10 mm EDTA and 10 mm NaF as inhibitors indicated that alkaline phosphate is predominantly located in the microvillous region of the adsorptive cells, while acid phosphatase is located in small particles distributed between the brush borders and the nuclei of these cells. Alkaline phosphatase activity was found to interfere with the localization of acid phosphatase unless EDTA was included in the incubation medium. A modified Gomori medium, containing 10 mm EDTA and additional lead nitrate, is described. Latency experiemtns using this medium, with unfixed sections, indicated the lysosomal nature of particulate acid phosphatase. The discussion stresses the importance of including an aldaline phosphatase inhibitor in incubation media designed to localize extralysosomal acid phosphatase activity.", "contents": "Acid hydrolases in the suckling rat small intestine. II. On the importance of alkaline phosphatase inhibition in the histochemical localization of acid phosphatase activity. Phosphatase activities against beta-glycerophosphate, I-naphthyl phosphate and naphthol AS-TR phosphate were investigated, at acid and aldaline pH levels, using unfixed and fixed cryostat sections of suckling rat jejunum. The use of 10 mm EDTA and 10 mm NaF as inhibitors indicated that alkaline phosphate is predominantly located in the microvillous region of the adsorptive cells, while acid phosphatase is located in small particles distributed between the brush borders and the nuclei of these cells. Alkaline phosphatase activity was found to interfere with the localization of acid phosphatase unless EDTA was included in the incubation medium. A modified Gomori medium, containing 10 mm EDTA and additional lead nitrate, is described. Latency experiemtns using this medium, with unfixed sections, indicated the lysosomal nature of particulate acid phosphatase. The discussion stresses the importance of including an aldaline phosphatase inhibitor in incubation media designed to localize extralysosomal acid phosphatase activity."}
{"id": "PMID:236270", "title": "Alcian Blue staining of cartilage for electron microscopy. Application of the critical electrolyte concentation principle.", "content": "The critical electrolyte concentration principle was applied to the Alcian Blue staining of rat epiphyseal cartilage proteoglycans for electron microscopy. The distribution and structure of material in glutaraldehyde-fixed cartilage stained at pH 5.8 without MgCl2 and in the presence of 0.05, 0.4, 0.5, 0.9 and 1.0 M MgCl2 was compared with that produced by simultaneous staining and fixation at neutral pH. Both methods resulted in staining of intracellular material within vacuoles as well as staining of non-collagenous matrix material. The structure and distribution of Alcian Blue-positive matrix material consisted of rounded or polygonal granules which accumulated around cells in the proliferative and hypertrophied zones. A similar pattern of distribution was observed in samples stained in the presence of 0.4 or 0.5 M MgCl2. In these cases, however, the stained material exhibited a ribbon-like configuration and granules were few in number. Increasing the MgCl2 concentration to 1.0 M resulted in a marked reduction of Alcian Blue stained material. No ribbon-like structures were observed, and matrix granules were reduced in both number and size. The decreased staining associated with increased electrolyte concentration lends support to the concept that epiphyseal cartilage matrix granules are composed primarily of chondroitin sulphate, and suggest that this same material is present in vacuoles associated with the Golgi apparatus in chondrocytes of the proliferative and hypertrophying zones.", "contents": "Alcian Blue staining of cartilage for electron microscopy. Application of the critical electrolyte concentation principle. The critical electrolyte concentration principle was applied to the Alcian Blue staining of rat epiphyseal cartilage proteoglycans for electron microscopy. The distribution and structure of material in glutaraldehyde-fixed cartilage stained at pH 5.8 without MgCl2 and in the presence of 0.05, 0.4, 0.5, 0.9 and 1.0 M MgCl2 was compared with that produced by simultaneous staining and fixation at neutral pH. Both methods resulted in staining of intracellular material within vacuoles as well as staining of non-collagenous matrix material. The structure and distribution of Alcian Blue-positive matrix material consisted of rounded or polygonal granules which accumulated around cells in the proliferative and hypertrophied zones. A similar pattern of distribution was observed in samples stained in the presence of 0.4 or 0.5 M MgCl2. In these cases, however, the stained material exhibited a ribbon-like configuration and granules were few in number. Increasing the MgCl2 concentration to 1.0 M resulted in a marked reduction of Alcian Blue stained material. No ribbon-like structures were observed, and matrix granules were reduced in both number and size. The decreased staining associated with increased electrolyte concentration lends support to the concept that epiphyseal cartilage matrix granules are composed primarily of chondroitin sulphate, and suggest that this same material is present in vacuoles associated with the Golgi apparatus in chondrocytes of the proliferative and hypertrophying zones."}
{"id": "PMID:236271", "title": "Isolation of two new related peptide antibiotics, cerexins A and B (studies on antibiotics from the genus Bacillus. I).", "content": "Two new antibiotics cerexins A and B were isolated from different strains identified with Bacillus cereus. These two antibiotics are amphoteric in nature, soluble in particular solvents such as dimethylsulfoxide, dimethylformamide and alkaline water, and show typical infrared absorptions of peptide. These also have similar antimicrobial properties active against gram-postive bacteria.", "contents": "Isolation of two new related peptide antibiotics, cerexins A and B (studies on antibiotics from the genus Bacillus. I). Two new antibiotics cerexins A and B were isolated from different strains identified with Bacillus cereus. These two antibiotics are amphoteric in nature, soluble in particular solvents such as dimethylsulfoxide, dimethylformamide and alkaline water, and show typical infrared absorptions of peptide. These also have similar antimicrobial properties active against gram-postive bacteria."}
{"id": "PMID:236272", "title": "Isolation and purification of blasticidin S deaminase from Aspergillus terreus.", "content": "An enzyme catalyzing the deamination of the cytosine moiety of blasticidin S was extracted from a fungal strain that belongs to Aspergillus terreus. The enzyme was purified with ammonium sulfate fractionation, Sephadex G-100 column and DEAE cellulose column chromatography, followed by preparative polyacrylamide gel electrophoresis. Blasticidin S deaminase could be separated easily from co-existing cytidine deaminase by DEAE column chromatography or gel electrophoresis, and preliminary study on the substrate specificity showed that this enzyme acts on blasticidin S derivatives, such as cytomycin and acetylblasticidin S, but not on cytosine, cytidine, purine bases or their nucleosides. Blasticidin S deaminase could be induced by the addition of blasticidin S to the culture, and sulfhydryl compounds, such as mercaptoethanol, were effective in protecting the enzyme from inactivation. The homogeneity of the enzyme was examined by both sedimentation analysis and polyacrylamide gel electrophoresis. The molecular weight and isoelectric point were found to be around 30,000 and 4.35, respectively. Some other properties were also examined.", "contents": "Isolation and purification of blasticidin S deaminase from Aspergillus terreus. An enzyme catalyzing the deamination of the cytosine moiety of blasticidin S was extracted from a fungal strain that belongs to Aspergillus terreus. The enzyme was purified with ammonium sulfate fractionation, Sephadex G-100 column and DEAE cellulose column chromatography, followed by preparative polyacrylamide gel electrophoresis. Blasticidin S deaminase could be separated easily from co-existing cytidine deaminase by DEAE column chromatography or gel electrophoresis, and preliminary study on the substrate specificity showed that this enzyme acts on blasticidin S derivatives, such as cytomycin and acetylblasticidin S, but not on cytosine, cytidine, purine bases or their nucleosides. Blasticidin S deaminase could be induced by the addition of blasticidin S to the culture, and sulfhydryl compounds, such as mercaptoethanol, were effective in protecting the enzyme from inactivation. The homogeneity of the enzyme was examined by both sedimentation analysis and polyacrylamide gel electrophoresis. The molecular weight and isoelectric point were found to be around 30,000 and 4.35, respectively. Some other properties were also examined."}
{"id": "PMID:236273", "title": "Cardiorespiratory effects of rapid saline infusion in normal man.", "content": "We have studied the cardiorespiratory effects of the rapid infusion (100 ml/min) of 2 liters of saline in four normal seated subjects. Cardiac output and pulmonary arterial pressure increased, while vital capacity (VC) and total lung capacity (TLC) decreased. There was an increase in closing volume (CV) without any detectable change in lung compliance or flow-volume characteristics. There was an increase in Pao2 during infusion period which can be related to better matching of ventilation to perfusion and to improved hemoglobin transport. In the recovery stage as cardiac output, pulmonary arterial pressure, TLC, and VC all returned toward control values CV remained high. In two subjects CV occurred within the normal tidal range of ventilation and in these two subjects Pao2 fell significantly below values obtained in the control period. The results suggest that rapid saline infusion in man can cause interstitial edema and lead to premature airway closure and hypoxemia.", "contents": "Cardiorespiratory effects of rapid saline infusion in normal man. We have studied the cardiorespiratory effects of the rapid infusion (100 ml/min) of 2 liters of saline in four normal seated subjects. Cardiac output and pulmonary arterial pressure increased, while vital capacity (VC) and total lung capacity (TLC) decreased. There was an increase in closing volume (CV) without any detectable change in lung compliance or flow-volume characteristics. There was an increase in Pao2 during infusion period which can be related to better matching of ventilation to perfusion and to improved hemoglobin transport. In the recovery stage as cardiac output, pulmonary arterial pressure, TLC, and VC all returned toward control values CV remained high. In two subjects CV occurred within the normal tidal range of ventilation and in these two subjects Pao2 fell significantly below values obtained in the control period. The results suggest that rapid saline infusion in man can cause interstitial edema and lead to premature airway closure and hypoxemia."}
{"id": "PMID:236274", "title": "Effect of circulating FFA on lactate production by skeletal muscle during stimulation.", "content": "The present experiments were undertaken to study the effects of FFA on lactate production by skeletal muscle during stimulation. In the first group, dogs were anesthetized with sodium pentobarbital and given no anticoagulant. The second group was also anesthetized with sodium pentobarbital but in addition given heparin and a fat-albumin infusion to elevate FFA. Stimulating the nerves to a group of skeletal muscles in the hindlimb (1.5/s) increased muscle blood flow 2.4-fold in both groups. In the first group stimulation did not alter the arteriovenous difference of lactate across the muscles. The difference was close to zero before and during stimulation. However in the second group, in which FFA were elevated, stimulation produced a large increase in muscle lactate production. In both groups there were no differences in the L/P ratio of muscle venous blood during stimulation. These results indicate that an increase in lactate production following muscle stimulation is not necessarily related to a state of tissue hypoxia.", "contents": "Effect of circulating FFA on lactate production by skeletal muscle during stimulation. The present experiments were undertaken to study the effects of FFA on lactate production by skeletal muscle during stimulation. In the first group, dogs were anesthetized with sodium pentobarbital and given no anticoagulant. The second group was also anesthetized with sodium pentobarbital but in addition given heparin and a fat-albumin infusion to elevate FFA. Stimulating the nerves to a group of skeletal muscles in the hindlimb (1.5/s) increased muscle blood flow 2.4-fold in both groups. In the first group stimulation did not alter the arteriovenous difference of lactate across the muscles. The difference was close to zero before and during stimulation. However in the second group, in which FFA were elevated, stimulation produced a large increase in muscle lactate production. In both groups there were no differences in the L/P ratio of muscle venous blood during stimulation. These results indicate that an increase in lactate production following muscle stimulation is not necessarily related to a state of tissue hypoxia."}
{"id": "PMID:236275", "title": "A respiratory venous chemoreceptor in the young puppy.", "content": "An extracorporeal venovenous shunt system utilizing a membrane oxygenator to alter venous blood gases was used to study the regulation of ventilation in 28 newborn and 4 adult dogs. There was no effect of the extracorporeal circuit per se (without the oxygenator in the system) on essential cardiovascular or respiratory function. When the puppies were placed on the extracorporeal circuit with the oxygenator in the system to effect changes in mixed venous blood gas composition there was a significant increase in venous P02 (Pv02), a decrease in venous Pco2 (Pvco2), a rise in venous pH (PHv), and a marked fall in minute ventilation (VE). There were no significant changes in cardiovascular function or arterial blood gases to account for the depression of ventilation. Acute changes in Pvo2 produced appropriate directional changes of VE under conditions where other arterial and venous blood gases were held constant. At a low Pvco2/Paco2 ratio, ventilation was depressed compared to those conditions with a high ratio. At any Pvc02/Paco2 ratio, ventilation could be depressed by raising the Pvo2. In adult animals ventilation could not be altered by changing venous blood gases. These experiments support the existence of a respiratory chemoreceptor sensitive to both PO2 and PCO2 in the prepulmonary or venous circulation of the newborn animal.", "contents": "A respiratory venous chemoreceptor in the young puppy. An extracorporeal venovenous shunt system utilizing a membrane oxygenator to alter venous blood gases was used to study the regulation of ventilation in 28 newborn and 4 adult dogs. There was no effect of the extracorporeal circuit per se (without the oxygenator in the system) on essential cardiovascular or respiratory function. When the puppies were placed on the extracorporeal circuit with the oxygenator in the system to effect changes in mixed venous blood gas composition there was a significant increase in venous P02 (Pv02), a decrease in venous Pco2 (Pvco2), a rise in venous pH (PHv), and a marked fall in minute ventilation (VE). There were no significant changes in cardiovascular function or arterial blood gases to account for the depression of ventilation. Acute changes in Pvo2 produced appropriate directional changes of VE under conditions where other arterial and venous blood gases were held constant. At a low Pvco2/Paco2 ratio, ventilation was depressed compared to those conditions with a high ratio. At any Pvc02/Paco2 ratio, ventilation could be depressed by raising the Pvo2. In adult animals ventilation could not be altered by changing venous blood gases. These experiments support the existence of a respiratory chemoreceptor sensitive to both PO2 and PCO2 in the prepulmonary or venous circulation of the newborn animal."}
{"id": "PMID:236276", "title": "Effect of chronic hypercapnia on body temperature regulation.", "content": "Guinea pigs and rats exposed to 15% CO2 for 7 days showed a parallel time course of changes in pH, body temperature (TB), and oxygen consumption (VO2). Between 1 and 6 h of exposure the maximal drop in actual pH occurred in guinea pigs simultaneously with the maximal fall in TB and VO2. During the subsequent period pH TB, VO2 rose again. Skin blood content (heat loss) also exhibited a biphasic pH-dependent time course. Animals showing no partial compensation of respiratory acidosis during 3 days exposure also failed in raising their TB back to normal in this time. The behavior of TB was found to be a good indicator of the acid-base status and adaptive potential of the animals to hypercapnia. Similar results were obtained in rats. Thermo-regulatory processes in the hypothalamus were affected during exposure to 15% CO2. Both guinea pigs and rats showed a decrease in norepinephrine content of the hypothalamus during the first part of exposure reaching a maximal fall at the end of 24 h. The serotonin content increased slightly during this period. During prolonged exposure to 3% CO2 for 7 days, TB showed a transient rise, and VO2 was slightly elevated.", "contents": "Effect of chronic hypercapnia on body temperature regulation. Guinea pigs and rats exposed to 15% CO2 for 7 days showed a parallel time course of changes in pH, body temperature (TB), and oxygen consumption (VO2). Between 1 and 6 h of exposure the maximal drop in actual pH occurred in guinea pigs simultaneously with the maximal fall in TB and VO2. During the subsequent period pH TB, VO2 rose again. Skin blood content (heat loss) also exhibited a biphasic pH-dependent time course. Animals showing no partial compensation of respiratory acidosis during 3 days exposure also failed in raising their TB back to normal in this time. The behavior of TB was found to be a good indicator of the acid-base status and adaptive potential of the animals to hypercapnia. Similar results were obtained in rats. Thermo-regulatory processes in the hypothalamus were affected during exposure to 15% CO2. Both guinea pigs and rats showed a decrease in norepinephrine content of the hypothalamus during the first part of exposure reaching a maximal fall at the end of 24 h. The serotonin content increased slightly during this period. During prolonged exposure to 3% CO2 for 7 days, TB showed a transient rise, and VO2 was slightly elevated."}
{"id": "PMID:236277", "title": "Autolysis of Neisseria gonorrhoeae.", "content": "Physiological conditions that would provide maximal rates of autolysis of Neisseria gonorrhoeae were examined. Autolysis was found to occur over a broad pH range with the optimum at pH 9.0 IN 0.05 M tris(hydroxymethyl)amino-methane-maleate buffer. The temperature optimum was found to be 40 C. Potassium ions greatly stimulated autolysis at a concentration of 0.01 M. Exposure of growing N. gonorrhoeae cells to penicillin, vancomycin, or D-cycloserine influenced the susceptibility to the autolysis, whereas chloramphenicol afforded some protection against autolysis. The primary structure of the peptidoglycan is composed of muramic acid/glutamic acid/alanine/diaminopimelic acid/glucosamine in approximate molar ratios of 1:1:2:1:1, respectively. Exogenous radioactive diaminopimelic acid, D-glucosamine, and D-alanine were incorporated into peptidoglycan. During autolysis these radioactive fragments were released from cells.", "contents": "Autolysis of Neisseria gonorrhoeae. Physiological conditions that would provide maximal rates of autolysis of Neisseria gonorrhoeae were examined. Autolysis was found to occur over a broad pH range with the optimum at pH 9.0 IN 0.05 M tris(hydroxymethyl)amino-methane-maleate buffer. The temperature optimum was found to be 40 C. Potassium ions greatly stimulated autolysis at a concentration of 0.01 M. Exposure of growing N. gonorrhoeae cells to penicillin, vancomycin, or D-cycloserine influenced the susceptibility to the autolysis, whereas chloramphenicol afforded some protection against autolysis. The primary structure of the peptidoglycan is composed of muramic acid/glutamic acid/alanine/diaminopimelic acid/glucosamine in approximate molar ratios of 1:1:2:1:1, respectively. Exogenous radioactive diaminopimelic acid, D-glucosamine, and D-alanine were incorporated into peptidoglycan. During autolysis these radioactive fragments were released from cells."}
{"id": "PMID:236278", "title": "Thiolases of Escherichia coli: purification and chain length specificities.", "content": "The presence of only one thiolase (EC 2.3.1.9) in wild-type Escherichia coli induced for enzymes of beta oxidation was demonstrated. A different thiolase was shown to be present in a mutant constitutive for the enzymes of butyrate degradation. The two thiolases were purified to near homogeneity by a simple two-step procedure and were found to be associated with different proteins as shown by gel electrophoresis. The thiolase isolated from induced wild-type Escherichia coli cell was active on beta-ketoacyl-coenzyme A derivatives containing 4 to 16 carbons, but exhibited optimal activity with medium-chain substrates. In contrast, the thiolase isolated from the constitutive mutant was shown to be specific for acetoacetyl-coenzyme A.", "contents": "Thiolases of Escherichia coli: purification and chain length specificities. The presence of only one thiolase (EC 2.3.1.9) in wild-type Escherichia coli induced for enzymes of beta oxidation was demonstrated. A different thiolase was shown to be present in a mutant constitutive for the enzymes of butyrate degradation. The two thiolases were purified to near homogeneity by a simple two-step procedure and were found to be associated with different proteins as shown by gel electrophoresis. The thiolase isolated from induced wild-type Escherichia coli cell was active on beta-ketoacyl-coenzyme A derivatives containing 4 to 16 carbons, but exhibited optimal activity with medium-chain substrates. In contrast, the thiolase isolated from the constitutive mutant was shown to be specific for acetoacetyl-coenzyme A."}
{"id": "PMID:236279", "title": "Multiple forms of 7-alpha-hydroxysteroid dehydrogenase in selected strains of Bacteroides fragilis.", "content": "Multiple forms of 7-alpha-hydroxysteroid dehydrogenase were detected in six of nine strains of Bacteroides fragilis. The enzymes differed with respect to pyridine nucleotide specificity, thermal stability, divalent metal cation requirement, and elution profilies from Sephadex G-200 columns. The nicotinamide adenine dinucleotide phosphate (NADP)-dependent enzyme required divalent metal cations, preferentially Mn-2+ (Km, 57 muM), for maximum catalytic activity. The NADP-dependent enzyme was labile at 65 C for 10 min, whereas the nicotinamide adenine dinucleotide (NAD)-dependent enzyme was stable at 65 C for 10 min. The specific activity of both the NAD- and NADP-dependent enzymes in crude extracts increased markedly (15- and 7.5-fold, respectively) during the transition from exponential- to stationary-phase growth in glucose medium containing 0.5 mM sodium cholate. The time course of apparent enzyme induction correlated temporally with the transformation of the 7-alpha-hydroxy group of cholate in the culture supernatant fluid. Both NAD- and NADP-dependent 7-alpha-hydroxysteroid dehydrogenase activities were found to be widely, but not universally, distributed in different strains and subspecies of B. fragilis. No NAD- or NADP-dependent 7-alpha-hydroxysteroid dehydrogenase activity could be detected in B. fragilis subsp. vulgatus Virginia Polytechnic Institute (VPI) no. 4245, subsp. thetaiotaomicron VPI 0061-1, or subsp. distasonis VPI 4243.", "contents": "Multiple forms of 7-alpha-hydroxysteroid dehydrogenase in selected strains of Bacteroides fragilis. Multiple forms of 7-alpha-hydroxysteroid dehydrogenase were detected in six of nine strains of Bacteroides fragilis. The enzymes differed with respect to pyridine nucleotide specificity, thermal stability, divalent metal cation requirement, and elution profilies from Sephadex G-200 columns. The nicotinamide adenine dinucleotide phosphate (NADP)-dependent enzyme required divalent metal cations, preferentially Mn-2+ (Km, 57 muM), for maximum catalytic activity. The NADP-dependent enzyme was labile at 65 C for 10 min, whereas the nicotinamide adenine dinucleotide (NAD)-dependent enzyme was stable at 65 C for 10 min. The specific activity of both the NAD- and NADP-dependent enzymes in crude extracts increased markedly (15- and 7.5-fold, respectively) during the transition from exponential- to stationary-phase growth in glucose medium containing 0.5 mM sodium cholate. The time course of apparent enzyme induction correlated temporally with the transformation of the 7-alpha-hydroxy group of cholate in the culture supernatant fluid. Both NAD- and NADP-dependent 7-alpha-hydroxysteroid dehydrogenase activities were found to be widely, but not universally, distributed in different strains and subspecies of B. fragilis. No NAD- or NADP-dependent 7-alpha-hydroxysteroid dehydrogenase activity could be detected in B. fragilis subsp. vulgatus Virginia Polytechnic Institute (VPI) no. 4245, subsp. thetaiotaomicron VPI 0061-1, or subsp. distasonis VPI 4243."}
{"id": "PMID:236280", "title": "Effect of aeration and sodium on the metabolism of citrate by Klebsiella aerogenes.", "content": "Anaerobic growth of Klebsiella aerogenes NCDO 711 (NCTC 418) on citrate was dependent on the presence of Na+ in the medium, and fermentation of citrate was mediated via the fermentation pathway enzymes, citrate lyase and a Na+-dependent oxalacetate decarboxylase. This confirms the previous findings on strain NCTC 418. Growth under aerobic conditions was independent of Na+. The mean generation time for cells grown aerobically on either Na+ or K+ citrate medium was about 60 min, with a molar growth yield of about 40 g (dry weight) of cells per mol of citrate utilized. Citrate was apparently metabolized aerobically in both the Na+ and K+ citrate cells via the citric acid cycle, since cell extracts contained alpha-ketoglutarate dehydrogenase but not the citrate fermentation enzymes. The presence of theother enzymes of the citric acid cycle in K. aerogenes was shown in earlier studies. Under aerated conditions (no detectable oxygen tension in the culture), growth was faster on the Na+ citrate medium (mean generation time, 85 min) than on the K+ citrate medium (mean generation time, 120 min). Both cultures grew slower than under aerobic conditions, presumably because of oxygen limitation. Despite the faster growth rate, the molar growth yield of the aerated Na+ citrate culture was one-half that observed for the aerated K+ citrate culture. Citrate was metabolized via the citric acid cycle in cells grown in the K+ citrate medium under aerated conditions since alpha-ketoglutarate dehydrogenase, but not the fermentation enzymes, was detected in extracts prepared from these cells. Metabolism of citrate in the Na+ citrate medium under aerated conditions occurred via both the fermentation pathway (approximately 75 percent) and the citric acid cycle (about 25 percent), as evidenced by (i) the presence of the fermentation enzymes and alpha-ketoglutarate dehydrogenase in extracts of cells grown under these conditions, (ii) a molar growth yield which was intermediate between that obtained for anaerobic and aerated K+ citrate cultures, and (iii) the excretion of acetate, which also occurred in anaerobic cultures but not in aerated K+ citrate or aerobic cultures.", "contents": "Effect of aeration and sodium on the metabolism of citrate by Klebsiella aerogenes. Anaerobic growth of Klebsiella aerogenes NCDO 711 (NCTC 418) on citrate was dependent on the presence of Na+ in the medium, and fermentation of citrate was mediated via the fermentation pathway enzymes, citrate lyase and a Na+-dependent oxalacetate decarboxylase. This confirms the previous findings on strain NCTC 418. Growth under aerobic conditions was independent of Na+. The mean generation time for cells grown aerobically on either Na+ or K+ citrate medium was about 60 min, with a molar growth yield of about 40 g (dry weight) of cells per mol of citrate utilized. Citrate was apparently metabolized aerobically in both the Na+ and K+ citrate cells via the citric acid cycle, since cell extracts contained alpha-ketoglutarate dehydrogenase but not the citrate fermentation enzymes. The presence of theother enzymes of the citric acid cycle in K. aerogenes was shown in earlier studies. Under aerated conditions (no detectable oxygen tension in the culture), growth was faster on the Na+ citrate medium (mean generation time, 85 min) than on the K+ citrate medium (mean generation time, 120 min). Both cultures grew slower than under aerobic conditions, presumably because of oxygen limitation. Despite the faster growth rate, the molar growth yield of the aerated Na+ citrate culture was one-half that observed for the aerated K+ citrate culture. Citrate was metabolized via the citric acid cycle in cells grown in the K+ citrate medium under aerated conditions since alpha-ketoglutarate dehydrogenase, but not the fermentation enzymes, was detected in extracts prepared from these cells. Metabolism of citrate in the Na+ citrate medium under aerated conditions occurred via both the fermentation pathway (approximately 75 percent) and the citric acid cycle (about 25 percent), as evidenced by (i) the presence of the fermentation enzymes and alpha-ketoglutarate dehydrogenase in extracts of cells grown under these conditions, (ii) a molar growth yield which was intermediate between that obtained for anaerobic and aerated K+ citrate cultures, and (iii) the excretion of acetate, which also occurred in anaerobic cultures but not in aerated K+ citrate or aerobic cultures."}
{"id": "PMID:236281", "title": "Methylamine and ammonia transport in Saccharomyces cerevisiae.", "content": "Methylamine (methylammonium ion) entered Saccharomyces cerevisiae X2180-A by means of a specific active transport system. Methylamine uptake was pH dependent (maximum rate between pH 6.0 and 6.5) and temperature dependent (increasing up to 35 C) and required the presence of a fermentable or oxidizable energy source in the growth medium. At 23 C the vmax for methylamine transport was similar 17 nmol/min per mg of cells (dry weight) and the apparent Km was 220 muM. The transport system exhibited maximal activity in ammonia-grown cells and was repressed 60 to 70 percent when glutamine or asparagine was added to the growth medium. There was no significant derepression of the transport system during nitrogen starvation. Ammonia (ammonium ion) was a strong competitive inhibitor of methylamine uptake, whereas other amines inhibited to a much lesser extent. Mutants selected on the basis of their reduced ability to transport methylamine (Mea-R) simultaneously exhibited a decreased ability to transport ammonia.", "contents": "Methylamine and ammonia transport in Saccharomyces cerevisiae. Methylamine (methylammonium ion) entered Saccharomyces cerevisiae X2180-A by means of a specific active transport system. Methylamine uptake was pH dependent (maximum rate between pH 6.0 and 6.5) and temperature dependent (increasing up to 35 C) and required the presence of a fermentable or oxidizable energy source in the growth medium. At 23 C the vmax for methylamine transport was similar 17 nmol/min per mg of cells (dry weight) and the apparent Km was 220 muM. The transport system exhibited maximal activity in ammonia-grown cells and was repressed 60 to 70 percent when glutamine or asparagine was added to the growth medium. There was no significant derepression of the transport system during nitrogen starvation. Ammonia (ammonium ion) was a strong competitive inhibitor of methylamine uptake, whereas other amines inhibited to a much lesser extent. Mutants selected on the basis of their reduced ability to transport methylamine (Mea-R) simultaneously exhibited a decreased ability to transport ammonia."}
{"id": "PMID:236282", "title": "Purification and properties of streptococcal nicotinamide adenine dinucleotide glycohydrolase.", "content": "Highly purified streptococcal nicotinamide adenine dinucleotide glycohydrolase (NADase) was obtained by utilizing disodium tetrathionate to protect the enzyme by blocking the sulfhydryl groups of streptococcal proteinase. This was followed by two-step ion-exchange chromatography. The pure enzyme, demonstrated as a single band on sodium dodecyl sulfate/polyacrylamide gel electrophoresis, had a specific activity of 11,200 NADase units per mg of protein and was devoid of hemolytic activity. NADase had a molecular weight of about 55,000 as determined by gel filtration, by summation of amino acid residues, and by sodium dodecyl sulfate/gel electrophoresis. The purified enzyme had optimal activity at pH 7.3 and at 40 C and a calculated Km of 5.1 times 10- minus 4 mM. It was inhibited by alpha-iodoacetamide.", "contents": "Purification and properties of streptococcal nicotinamide adenine dinucleotide glycohydrolase. Highly purified streptococcal nicotinamide adenine dinucleotide glycohydrolase (NADase) was obtained by utilizing disodium tetrathionate to protect the enzyme by blocking the sulfhydryl groups of streptococcal proteinase. This was followed by two-step ion-exchange chromatography. The pure enzyme, demonstrated as a single band on sodium dodecyl sulfate/polyacrylamide gel electrophoresis, had a specific activity of 11,200 NADase units per mg of protein and was devoid of hemolytic activity. NADase had a molecular weight of about 55,000 as determined by gel filtration, by summation of amino acid residues, and by sodium dodecyl sulfate/gel electrophoresis. The purified enzyme had optimal activity at pH 7.3 and at 40 C and a calculated Km of 5.1 times 10- minus 4 mM. It was inhibited by alpha-iodoacetamide."}
{"id": "PMID:236283", "title": "Nucleolytic degradation of homologous and heterologous deoxyribonucleic acid molecules at the surface of competent pneumococci.", "content": "Competent pneumococci can catalyze the rapid and quantitative degradation of extracellular deocyribonucleic acid (DNA) molecules through the activity of surface-located nucleases (endo- and, possibly, exonucleases as well). Both homologous and heterologous DNAs are degraded by a mechanism that seems to involve a cyclic process: (i) attachment of DNA to the cell surface followed by (ii) nucleolytic attack, and (iii) release to the medium. Processes (ii) and (iii) are both inhibited by ethylenediaminetetraacetate. Whereas surface nuclease activity is specific for competent cells, the bulk of this activity is not coupled to irreversible DNA uptake (deoxyribonuclease-resistant binding). Pneumococcal DNA treated with ultraviolet irradiation or nitrous acid (cross-linking?) is selectively impaired in the ability to irreversibly bind to competent cells, whereas reversible binding is normal.", "contents": "Nucleolytic degradation of homologous and heterologous deoxyribonucleic acid molecules at the surface of competent pneumococci. Competent pneumococci can catalyze the rapid and quantitative degradation of extracellular deocyribonucleic acid (DNA) molecules through the activity of surface-located nucleases (endo- and, possibly, exonucleases as well). Both homologous and heterologous DNAs are degraded by a mechanism that seems to involve a cyclic process: (i) attachment of DNA to the cell surface followed by (ii) nucleolytic attack, and (iii) release to the medium. Processes (ii) and (iii) are both inhibited by ethylenediaminetetraacetate. Whereas surface nuclease activity is specific for competent cells, the bulk of this activity is not coupled to irreversible DNA uptake (deoxyribonuclease-resistant binding). Pneumococcal DNA treated with ultraviolet irradiation or nitrous acid (cross-linking?) is selectively impaired in the ability to irreversibly bind to competent cells, whereas reversible binding is normal."}
{"id": "PMID:236284", "title": "Effect of lysozyme on ionic forms of spores of Clostridium perfringens type A.", "content": "H spores of Clostridium perfringens type A (two strains) were more sensitive to germination by lysozyme than native spores. Resistance to lysozyme of H spores was restored by calcium loading.", "contents": "Effect of lysozyme on ionic forms of spores of Clostridium perfringens type A. H spores of Clostridium perfringens type A (two strains) were more sensitive to germination by lysozyme than native spores. Resistance to lysozyme of H spores was restored by calcium loading."}
{"id": "PMID:236285", "title": "Glyceraldehyde-3-phosphate dehydrogenase of horseshoe crab (Tachypleus tridentatus).", "content": "Glyceraldehyde-3-phosphate dehydrogenase [ED 1.2.1.12] was purified from the horseshoe crab, a living fossil, and its properties were examined.  1 The purified enzyme was homogeneous as judged by various tests.  The enzyme, like enzymes from other sources, was  a tetramer with a subunit molecular weight of 36,000.  The kinetic parameters and pH optimum were also similar to those of other enzymes, though the enzyme was more stable against heat and pH denaturations.  2 Analysis of SH groups showed that there were 4 SH groups per subunit, one of which was essential for the enzyme activity and was highly reactive.  3. CD spectra of the enzyme suggested that the enzyme had a very high content of beta-structure (ca. 45 per cent).  4. The horseshoe crab enzyme could form a hybrid in vitro with the rabbit muscle enzymes in concentrated salt solution at acidic pH.  5. There results indicate that the enzyme has overall structural similarity to other enzymes and that the enzyme is highly conserved during a long period of evolution.  Some discussions on the structure and activity of the horseshoe crab enzyme are made in comparison with the enzymes from other sources.", "contents": "Glyceraldehyde-3-phosphate dehydrogenase of horseshoe crab (Tachypleus tridentatus). Glyceraldehyde-3-phosphate dehydrogenase [ED 1.2.1.12] was purified from the horseshoe crab, a living fossil, and its properties were examined.  1 The purified enzyme was homogeneous as judged by various tests.  The enzyme, like enzymes from other sources, was  a tetramer with a subunit molecular weight of 36,000.  The kinetic parameters and pH optimum were also similar to those of other enzymes, though the enzyme was more stable against heat and pH denaturations.  2 Analysis of SH groups showed that there were 4 SH groups per subunit, one of which was essential for the enzyme activity and was highly reactive.  3. CD spectra of the enzyme suggested that the enzyme had a very high content of beta-structure (ca. 45 per cent).  4. The horseshoe crab enzyme could form a hybrid in vitro with the rabbit muscle enzymes in concentrated salt solution at acidic pH.  5. There results indicate that the enzyme has overall structural similarity to other enzymes and that the enzyme is highly conserved during a long period of evolution.  Some discussions on the structure and activity of the horseshoe crab enzyme are made in comparison with the enzymes from other sources."}
{"id": "PMID:236286", "title": "Fructose-diphosphate aldolase of Horseshoe crab (Tachypleus tridentatus).", "content": "Fructose-diphosphate aldolase [ED 4.1.2.13] was isolated from horseshoe crab ( living fossil) muscle and some molecular and enzymatic properties were examined.  The enzyme was a tetramer with a molecular weight of about 160,000.  The enzyme activity was inhibited by reduction with borohydride in the presence of the substrate and was inactivated by carboxypeptidase A [EC 3.4.12.2] digestion.  The pH optima for fructose-diphosphate (FDP) and fructose-1-phosphate (F1P) activities were 6.5--8 and 7.5--8.2, respectively.  The ratio of FDP/F1P activities was 30 and Km values were 1.7 times 10- minus 5 M and 2.5 times 10- minus 3 M, respectively, for the two substrates.  The horseshoe crab aldolase was classified as class 1, type A, based on the results obtained.  Extensive homology in various properties of the enzyme was observed when it was compared with enzymes from other sources, though some differences could be found in the amino acid composition and in the kinetic properties.", "contents": "Fructose-diphosphate aldolase of Horseshoe crab (Tachypleus tridentatus). Fructose-diphosphate aldolase [ED 4.1.2.13] was isolated from horseshoe crab ( living fossil) muscle and some molecular and enzymatic properties were examined.  The enzyme was a tetramer with a molecular weight of about 160,000.  The enzyme activity was inhibited by reduction with borohydride in the presence of the substrate and was inactivated by carboxypeptidase A [EC 3.4.12.2] digestion.  The pH optima for fructose-diphosphate (FDP) and fructose-1-phosphate (F1P) activities were 6.5--8 and 7.5--8.2, respectively.  The ratio of FDP/F1P activities was 30 and Km values were 1.7 times 10- minus 5 M and 2.5 times 10- minus 3 M, respectively, for the two substrates.  The horseshoe crab aldolase was classified as class 1, type A, based on the results obtained.  Extensive homology in various properties of the enzyme was observed when it was compared with enzymes from other sources, though some differences could be found in the amino acid composition and in the kinetic properties."}
{"id": "PMID:236287", "title": "Participation of the catalytic carboxyls, Asp 52 and Glu 35, and Asp 101 in the binding of substrate analogues to hen lysozyme.", "content": "The interactions of the substrate analogues, GlcNAc, beta-methyl GlcNAc, (GlcNAc)2, and (GlcNAc)3, with turkey egg-white lysozyme [ED 3.2.1.17], in which the Asp 101 of hen lysozyme is replaced by Gly, were studied at various pH values by measuring changes in the circular dichroic (CD) band at 295 nm.  Results were compared with those for hen egg-white lysozyme.  The modes of binding of these substrate analogues to turkey lysozyme were very similar to those hen lysozyme except for the participation of Asp 101 in hen lysozyme.  The ionization constants of the catalytic carboxyls, Glu 35 and Asp 52, in the turkey lysozyme-(GlcNAc)3 complex were determined by measuring the pH dependence of the CD band at 304 nm, which originates from Trp 108 near the catalytic carboxyls.  The ionization behavior of the catalytic carboxyls of turkey lysozyme in the presence and absence of (GlcNAc)3 was essentially the same as that for hen lysozyme.  The pH dependence of the binding constant of (GlcNAc)3 to hen lysozyme was compared with that to turkey lysozyme between pH 2 and 8.  The pH dependence of the binding constant for (GlcNAc)3 to turkey lysozyme could be interpreted entirely in terms of perturbation of catalytic carboxyls.  In the case of hen lysozyme, it was interpreted in terms of perturbation of the catalytic carboxyls and Asp 101 in the substrate-binding site.  The pK values of Asp 101 in hen lysozyme and the hen lysozyme-(GLcNAc)3 complex were 4.5 and 3.4, respectively.  The binding constants of (GlcNAc)3 to lysozyme molecules with different microscopic protonation forms, with respect to the catalytic carboxyls, were estimated.  The binding constant of lysozyme, in which Asp 52 and Glu 35 are deprotonated, to (GlcNAc)3 was the smallest.  The other three species had similar binding constant to (GlcNAc)3.", "contents": "Participation of the catalytic carboxyls, Asp 52 and Glu 35, and Asp 101 in the binding of substrate analogues to hen lysozyme. The interactions of the substrate analogues, GlcNAc, beta-methyl GlcNAc, (GlcNAc)2, and (GlcNAc)3, with turkey egg-white lysozyme [ED 3.2.1.17], in which the Asp 101 of hen lysozyme is replaced by Gly, were studied at various pH values by measuring changes in the circular dichroic (CD) band at 295 nm.  Results were compared with those for hen egg-white lysozyme.  The modes of binding of these substrate analogues to turkey lysozyme were very similar to those hen lysozyme except for the participation of Asp 101 in hen lysozyme.  The ionization constants of the catalytic carboxyls, Glu 35 and Asp 52, in the turkey lysozyme-(GlcNAc)3 complex were determined by measuring the pH dependence of the CD band at 304 nm, which originates from Trp 108 near the catalytic carboxyls.  The ionization behavior of the catalytic carboxyls of turkey lysozyme in the presence and absence of (GlcNAc)3 was essentially the same as that for hen lysozyme.  The pH dependence of the binding constant of (GlcNAc)3 to hen lysozyme was compared with that to turkey lysozyme between pH 2 and 8.  The pH dependence of the binding constant for (GlcNAc)3 to turkey lysozyme could be interpreted entirely in terms of perturbation of catalytic carboxyls.  In the case of hen lysozyme, it was interpreted in terms of perturbation of the catalytic carboxyls and Asp 101 in the substrate-binding site.  The pK values of Asp 101 in hen lysozyme and the hen lysozyme-(GLcNAc)3 complex were 4.5 and 3.4, respectively.  The binding constants of (GlcNAc)3 to lysozyme molecules with different microscopic protonation forms, with respect to the catalytic carboxyls, were estimated.  The binding constant of lysozyme, in which Asp 52 and Glu 35 are deprotonated, to (GlcNAc)3 was the smallest.  The other three species had similar binding constant to (GlcNAc)3."}
{"id": "PMID:236288", "title": "Copurification of L-ascorbate-2-sulfate sulfohydrolase and arylsulfatase activities from the liver of a marine gastropod, Charonia lampas.", "content": "Ascorbate-2-sulfate sulfohydrolase was purified 184-fold from a crude extract of the liver of Charonia lampas.  In all purification steps including phosphocellulose, first and second Sephadex G-150 column chromatographies, the enzyme activity eluted together with arylsulfatase [ED 3.1.6.1] activity, and was separated from glycosulfatase ]EC 3.1.6.3] activity.  The nonidentity of ascorbate-2-sulfate sulfohydrolase and glycosulfatase was further confirmed by an isoelectric focussing study.  Ascorbate-2-sulfate sulfohydrolase had an isoelectric point, pI, of 4.9, and had maximum activity at pH 4.0.  Its molecular weight was estimated to be about 154.000.", "contents": "Copurification of L-ascorbate-2-sulfate sulfohydrolase and arylsulfatase activities from the liver of a marine gastropod, Charonia lampas. Ascorbate-2-sulfate sulfohydrolase was purified 184-fold from a crude extract of the liver of Charonia lampas.  In all purification steps including phosphocellulose, first and second Sephadex G-150 column chromatographies, the enzyme activity eluted together with arylsulfatase [ED 3.1.6.1] activity, and was separated from glycosulfatase ]EC 3.1.6.3] activity.  The nonidentity of ascorbate-2-sulfate sulfohydrolase and glycosulfatase was further confirmed by an isoelectric focussing study.  Ascorbate-2-sulfate sulfohydrolase had an isoelectric point, pI, of 4.9, and had maximum activity at pH 4.0.  Its molecular weight was estimated to be about 154.000."}
{"id": "PMID:236289", "title": "The aconitase of yeast.  II. Crystallization and general properties of yeast aconitase.", "content": "Yeast aconitase [citrate (isocitrate) hydro-lyase, ED 4.2.1.3], inductively formed by Candida iipolytica in the presence of fluoroacetate, was purified approximately 100-fold by Sephadex G-100 gel filtration and DEAE-Sephadex column chromatography, yielding dark-brown needle crystals.  The crystalline aconitase was homogenious as judged by polyacrylamide gel electrophoresis and sedimentation by ultracentrifugation.  The enzyme showed maximal activity at pH 8.0 and at 55 degrees.  It has an S20, W of 5.03 S, a molecular weight of 68,500 and an isolectric point of pH 4.2.  The presence of 2.10 moles of iron per mole of the enzyme was demonstrated by atomic absorption spectroscopy.", "contents": "The aconitase of yeast.  II. Crystallization and general properties of yeast aconitase. Yeast aconitase [citrate (isocitrate) hydro-lyase, ED 4.2.1.3], inductively formed by Candida iipolytica in the presence of fluoroacetate, was purified approximately 100-fold by Sephadex G-100 gel filtration and DEAE-Sephadex column chromatography, yielding dark-brown needle crystals.  The crystalline aconitase was homogenious as judged by polyacrylamide gel electrophoresis and sedimentation by ultracentrifugation.  The enzyme showed maximal activity at pH 8.0 and at 55 degrees.  It has an S20, W of 5.03 S, a molecular weight of 68,500 and an isolectric point of pH 4.2.  The presence of 2.10 moles of iron per mole of the enzyme was demonstrated by atomic absorption spectroscopy."}
{"id": "PMID:236290", "title": "Affinity chromatography of cysteine-containing histone.", "content": "Affinity chromatography based on the reaction between SH groups in protein and +HgC6H4CO groups in the p-mercuribenzoylaminoethyl derivative of Sepharose 4B was examined with a crude preparation of calf thymus cysteine-containing histone.  Adsorption of the histone onto the column by specific coupling was found to be optimal in 0.1 M citrate buffer, pH 5.5, containing 5M urea to prevent any aggregation of histones and their non-specific adsorption onto the column, and elution from the column was successfully performed by cleavage of the resulting S-Hg bond with urea-buffer solution containing 0.05 M 2-mercaptoethanol.  Under these conditions both the adsorption and elution were quantitative; no adsorption was observed when either SH-blocked histone or unsubstituted Sepharose was used.  The cysteine-containing histone thus recovered, after further purification by Bio-Gel P-60 chromatography to remove some cysteine-containing nonhistone proteins contaminating the starting material, showed a single band on polyacrylamide gel electrophoresis and an amino acid composition agreeing with the known sequence of this histone.", "contents": "Affinity chromatography of cysteine-containing histone. Affinity chromatography based on the reaction between SH groups in protein and +HgC6H4CO groups in the p-mercuribenzoylaminoethyl derivative of Sepharose 4B was examined with a crude preparation of calf thymus cysteine-containing histone.  Adsorption of the histone onto the column by specific coupling was found to be optimal in 0.1 M citrate buffer, pH 5.5, containing 5M urea to prevent any aggregation of histones and their non-specific adsorption onto the column, and elution from the column was successfully performed by cleavage of the resulting S-Hg bond with urea-buffer solution containing 0.05 M 2-mercaptoethanol.  Under these conditions both the adsorption and elution were quantitative; no adsorption was observed when either SH-blocked histone or unsubstituted Sepharose was used.  The cysteine-containing histone thus recovered, after further purification by Bio-Gel P-60 chromatography to remove some cysteine-containing nonhistone proteins contaminating the starting material, showed a single band on polyacrylamide gel electrophoresis and an amino acid composition agreeing with the known sequence of this histone."}
{"id": "PMID:236291", "title": "A new flavin enzyme catalyzing the reduction of dihydrodipicolinate in sporulating Bacillus subtilis I. Purification and properties.", "content": "A dihydrodipicolinate reductase containing flavin was purified from sporulating Bacillus subtilis PCI 219.  The purified enzyme appeared homogeneous by dise gel electrophoresis.  Its molecular weight was estimated as 74,000 by gel filtration on Sephadex G-200, and as 18,500 by electrophoresis on sodium dodecylsulfate polyacrylamid gel.  These results suggest that the enzyme is composed of four subunits.  The prosthetic group was identified as FMN, and one mole of the enzyme contained two moles of FMN.  Both NADPH and NADH acted as coenzyme, though NADH was less effective.  The enzyme also exhibited diaphorase activity.  The pH optimum was 6.1.  The enzyme was inhibited by dipicolinate but not by lysine or alpha, epsilon-diaminopimelate.", "contents": "A new flavin enzyme catalyzing the reduction of dihydrodipicolinate in sporulating Bacillus subtilis I. Purification and properties. A dihydrodipicolinate reductase containing flavin was purified from sporulating Bacillus subtilis PCI 219.  The purified enzyme appeared homogeneous by dise gel electrophoresis.  Its molecular weight was estimated as 74,000 by gel filtration on Sephadex G-200, and as 18,500 by electrophoresis on sodium dodecylsulfate polyacrylamid gel.  These results suggest that the enzyme is composed of four subunits.  The prosthetic group was identified as FMN, and one mole of the enzyme contained two moles of FMN.  Both NADPH and NADH acted as coenzyme, though NADH was less effective.  The enzyme also exhibited diaphorase activity.  The pH optimum was 6.1.  The enzyme was inhibited by dipicolinate but not by lysine or alpha, epsilon-diaminopimelate."}
{"id": "PMID:236292", "title": "A new flavin enzyme catalyzing the reduction of dihydrodipicolinate in sporulating Bacillus subtilis.  II. Kinetics and regulatory function.", "content": "Dihydrodipicolinate reductase in Bacillus subtilis PCI 219 had FMN as a prosthetic group, and the hydrogen transfer pathway is considered to be NADPH yields FMN yields dihydrodipicolinate.  Linewaver-Burk plots of the reciprocal of the activity against the reciprocal of the concentration of either of the two substrates, dihydrodipocolinate and NADPH, are consistent with a reaction mechanism involving interconversion of two free forms of the enzyme by the two substrates.  The Km values obtained from the secondary plots are 0.77 mM for dihydrodipicolinate and 72 muM for NADPH.  Inhibition by dipicolinate is competitive with NADPH and noncompetitive with dihydrodipicolinate, and shows positive cooperativity.  The possible metabolic role of the reductase in sporulating Bacillus subtilis is discussed in connection with regulation of the biosyntheses of dipicolinate and diaminopimelate.", "contents": "A new flavin enzyme catalyzing the reduction of dihydrodipicolinate in sporulating Bacillus subtilis.  II. Kinetics and regulatory function. Dihydrodipicolinate reductase in Bacillus subtilis PCI 219 had FMN as a prosthetic group, and the hydrogen transfer pathway is considered to be NADPH yields FMN yields dihydrodipicolinate.  Linewaver-Burk plots of the reciprocal of the activity against the reciprocal of the concentration of either of the two substrates, dihydrodipocolinate and NADPH, are consistent with a reaction mechanism involving interconversion of two free forms of the enzyme by the two substrates.  The Km values obtained from the secondary plots are 0.77 mM for dihydrodipicolinate and 72 muM for NADPH.  Inhibition by dipicolinate is competitive with NADPH and noncompetitive with dihydrodipicolinate, and shows positive cooperativity.  The possible metabolic role of the reductase in sporulating Bacillus subtilis is discussed in connection with regulation of the biosyntheses of dipicolinate and diaminopimelate."}
{"id": "PMID:236293", "title": "Beta-glucuronidase of rat preputial gland.  Crystallization, properties, carbohydrate composition, and subunits.", "content": "Rat preputial gland beta-glucuronidase [ED 3.2.1.31] was purified by ammonium sulfate precipitation, ethanol fractionation, gel filtration on Sephadex G-200 and crystallization.  The purified enzyme appeared homogeneous on electrophoresis in polyacrylamide gel, and on analytical ultracentrifugation and had a molecular weight of approximately 320,000, and a sedimentation coefficient of 12S.  SDS polyacrylamide gel electrophoresis indicated that the enzyme consisted of subunits with molecular weight of 79,000, so the native enzyme appeared to be a tetramer.  The Km with p-nitrophenyl beta-D-glucosiduronic acid as substrate was about 0.53 mM.  The enzyme had a single pH optimum at 4.5.  The enzyme had a very low content of sulphur-containing amino acid and contained 5.7 per cent carbohydrate, consisting of mannose, glucose, fucose, galactose, and glucosamine in a ratio of 44;9;6;2;41.  Sialic acid was not detected in the crystallized enzyme.", "contents": "Beta-glucuronidase of rat preputial gland.  Crystallization, properties, carbohydrate composition, and subunits. Rat preputial gland beta-glucuronidase [ED 3.2.1.31] was purified by ammonium sulfate precipitation, ethanol fractionation, gel filtration on Sephadex G-200 and crystallization.  The purified enzyme appeared homogeneous on electrophoresis in polyacrylamide gel, and on analytical ultracentrifugation and had a molecular weight of approximately 320,000, and a sedimentation coefficient of 12S.  SDS polyacrylamide gel electrophoresis indicated that the enzyme consisted of subunits with molecular weight of 79,000, so the native enzyme appeared to be a tetramer.  The Km with p-nitrophenyl beta-D-glucosiduronic acid as substrate was about 0.53 mM.  The enzyme had a single pH optimum at 4.5.  The enzyme had a very low content of sulphur-containing amino acid and contained 5.7 per cent carbohydrate, consisting of mannose, glucose, fucose, galactose, and glucosamine in a ratio of 44;9;6;2;41.  Sialic acid was not detected in the crystallized enzyme."}
{"id": "PMID:236294", "title": "Interaction of fibrinogen with detergent.", "content": "Both cationic and anionic detergents were found to precipitate fibrinogen by forming fibrinogen-detergent complexes.  These complexes were soluble in distilled water, but the aqueous solutions were very unstable and the complexes precipitated in the presence of salt.  In the interaction of fibrinogen with the cationic detergent, stearyltrimethyl-ammonium chloride, approximately 160 molecules of detergent were found to bind to one molecule of fibrinogen.  In distilled water, the fibrinogen-stearyltrimethylammonium complex (FG-STA(Cl)) remained soluble in the presence of thrombin [ED 3.4.21.5] although the same peptides were released as those released from fibrinogen.  Precipitation of FG-STA(Cl) by salt was found to be closely related to adsorption of the anion of the salt by the complex.  Futher addition of salt resulted in solubilization of the precipitate, and the solubilization was also due to further adsorption of the anion onto the precipitate.", "contents": "Interaction of fibrinogen with detergent. Both cationic and anionic detergents were found to precipitate fibrinogen by forming fibrinogen-detergent complexes.  These complexes were soluble in distilled water, but the aqueous solutions were very unstable and the complexes precipitated in the presence of salt.  In the interaction of fibrinogen with the cationic detergent, stearyltrimethyl-ammonium chloride, approximately 160 molecules of detergent were found to bind to one molecule of fibrinogen.  In distilled water, the fibrinogen-stearyltrimethylammonium complex (FG-STA(Cl)) remained soluble in the presence of thrombin [ED 3.4.21.5] although the same peptides were released as those released from fibrinogen.  Precipitation of FG-STA(Cl) by salt was found to be closely related to adsorption of the anion of the salt by the complex.  Futher addition of salt resulted in solubilization of the precipitate, and the solubilization was also due to further adsorption of the anion onto the precipitate."}
{"id": "PMID:236295", "title": "Structure and function of D-amino acid oxidase.  IX. Changes in the fluorescence polarization of FAD upon complex formation.", "content": "1. The fluorescence polarization, P, of FAD increased on complex formation with the apoenzyme of D-amino acid oxidase [D-amino acid: O2 ocidoreductase (deaminating), EC 1.4.3.3].  The time course of the increase was monophasic.  The values of P were extimated to be 0.04, 0.4, and 0.4 for FAD, the enzyme and the enzyme-benzoate complex, respectively.  2. The value of P of the enzyme is dependent on its concentration, indicating that the degrees of dissociation of FAD in the monomer and dimer are different.  The dissociation constant was calculated to be 7 times 10-minus 7 M for the monomeric form of the enzyme.  This value is far larger than the value for the dimeric form of the enzyme, 1 times 10-minus 8 M, calculated from equilibrium dialysis data.  3. Changes in fluorescence polarization of the enzyme due to changes in solution pH or temperature can be explained in terms of the monomer-dimer equilibrium.", "contents": "Structure and function of D-amino acid oxidase.  IX. Changes in the fluorescence polarization of FAD upon complex formation. 1. The fluorescence polarization, P, of FAD increased on complex formation with the apoenzyme of D-amino acid oxidase [D-amino acid: O2 ocidoreductase (deaminating), EC 1.4.3.3].  The time course of the increase was monophasic.  The values of P were extimated to be 0.04, 0.4, and 0.4 for FAD, the enzyme and the enzyme-benzoate complex, respectively.  2. The value of P of the enzyme is dependent on its concentration, indicating that the degrees of dissociation of FAD in the monomer and dimer are different.  The dissociation constant was calculated to be 7 times 10-minus 7 M for the monomeric form of the enzyme.  This value is far larger than the value for the dimeric form of the enzyme, 1 times 10-minus 8 M, calculated from equilibrium dialysis data.  3. Changes in fluorescence polarization of the enzyme due to changes in solution pH or temperature can be explained in terms of the monomer-dimer equilibrium."}
{"id": "PMID:236296", "title": "Galactose-6-phosphate dehydrogenase. Purification and partial characterization.", "content": "A new enzyme, galactose-6-phosphate dehydrogenase has been purified about 50-fold from goat liver. The enzyme can be distinguished from the nonspecific hexose-6-phosphate dehydrogenase and glucose-6-phosphate dehydrogenase by its high substrate specificity and absolute pyridine nucleotide requirement. In contrast to the hexose-6-phosphate dehydrogenase, this enzyme is located exclusively in the cytoplasmic fraction of the cell. The enzyme is a metalloprotein and is highly sensitive to mercurials. The product of the reaction is possibly a ketoaldose, phosphorylated at the primary alcoholic group.", "contents": "Galactose-6-phosphate dehydrogenase. Purification and partial characterization. A new enzyme, galactose-6-phosphate dehydrogenase has been purified about 50-fold from goat liver. The enzyme can be distinguished from the nonspecific hexose-6-phosphate dehydrogenase and glucose-6-phosphate dehydrogenase by its high substrate specificity and absolute pyridine nucleotide requirement. In contrast to the hexose-6-phosphate dehydrogenase, this enzyme is located exclusively in the cytoplasmic fraction of the cell. The enzyme is a metalloprotein and is highly sensitive to mercurials. The product of the reaction is possibly a ketoaldose, phosphorylated at the primary alcoholic group."}
{"id": "PMID:236297", "title": "Nicotinamide adenine dinucleotide phosphate-specific glutamate dehydrogenase of Neurospora.", "content": "Neurospora NADP-specific glutamate dehydrogenase that was treated with iodoacetate, iodoacetamide, or N-ethylmaleimide to block the thiol groups was cleaved with cyanogen bromide. Of the expected 10 peptides, based on a methionine content of 9 residues, 8 were obtained in pure form and 2 were handled as a mixture. The fragments ranged in size from 9 to 109 residues. In addition, there were isolated 6 peptides, produced by anomalous cleavage at the carboxyl groups of tryptophan residues, and two by hydrolysis of an aspartyl-proline bond. Preliminary separation of these peptides was accomplished by gel filtration followed by either ion-exchange chromatography of the larger peptides or by paper chromatography and paper electrophoresis of the smaller fragments. Ordering of the CNBr fragments in sequence was based upon sequences of tryptic and chymotryptic peptides obtained in another laboratory. The complete sequence of the protein is presented. The amino acid sequences of the bovine and chicken liver glutamate dehydrogenases previously determined show considerable homology with the NADP-specific enzyme of Neurospora in the NH2-terminal half of the molecule; this includes the region of the specifically reactive lysine residue and the portion of the sequence that has been implicated in coenzyme binding. Particularly striking is the fact that most of the residues conserved among the three homologous proteins would be expected to be important for conformational, rather than catalytic, effects. This implies that the conformation of the Neurospora enzyme must be similar in parts of its structure to the vertebrate enzymes but undoubtedly differs in some regards.", "contents": "Nicotinamide adenine dinucleotide phosphate-specific glutamate dehydrogenase of Neurospora. Neurospora NADP-specific glutamate dehydrogenase that was treated with iodoacetate, iodoacetamide, or N-ethylmaleimide to block the thiol groups was cleaved with cyanogen bromide. Of the expected 10 peptides, based on a methionine content of 9 residues, 8 were obtained in pure form and 2 were handled as a mixture. The fragments ranged in size from 9 to 109 residues. In addition, there were isolated 6 peptides, produced by anomalous cleavage at the carboxyl groups of tryptophan residues, and two by hydrolysis of an aspartyl-proline bond. Preliminary separation of these peptides was accomplished by gel filtration followed by either ion-exchange chromatography of the larger peptides or by paper chromatography and paper electrophoresis of the smaller fragments. Ordering of the CNBr fragments in sequence was based upon sequences of tryptic and chymotryptic peptides obtained in another laboratory. The complete sequence of the protein is presented. The amino acid sequences of the bovine and chicken liver glutamate dehydrogenases previously determined show considerable homology with the NADP-specific enzyme of Neurospora in the NH2-terminal half of the molecule; this includes the region of the specifically reactive lysine residue and the portion of the sequence that has been implicated in coenzyme binding. Particularly striking is the fact that most of the residues conserved among the three homologous proteins would be expected to be important for conformational, rather than catalytic, effects. This implies that the conformation of the Neurospora enzyme must be similar in parts of its structure to the vertebrate enzymes but undoubtedly differs in some regards."}
{"id": "PMID:236298", "title": "Purification of thymidine phosphorylase from Escherichia coli and its photoinactivation in the presence of thymine, thymidine, and some halogenated analogs.", "content": "Isoelectric focusing was used as the final step in the isolation of thymidine phosphorylase which was found to have an isoelectric point of 4.1. Analytical acrylamide gel electrophoresis showed the purified enzyme preparation contained one major protein band which stained for thymidine phosphorylase activity and usually a minor, faster migrating band devoid of activity. Inactivation of thymidine phosphorylase alone or in the presence of sensitizers by ultraviolet light, primarily at 253.7 nm, followed first order inactivation kinetics. The rate of inactivation of the enzyme was the same at pH 5 and 7.4 and the addition of various pyrimidine bases and nucleosides enhanced the inactivation rate at both pH values, but to a greater extent at pH 5. Linear plots of inactivation rates versus concentrations of thymidine or thymine were the same. At 7.8 mM thymidine or thymine, 11- and 4.4-fold increases in photoinactivation of thymidine phosphorylase were observed at pH 5 AND 7.4 RESPECTIVELY. Parabolic curves were obtained with increasing concentrations of either 5-iodo-2'-deoxyuridine or 5-iodouracil. 5-Iodouracil at 5.2 mM caused 212- (pH 5) and 100- (pH 7.4) FOLD INCREASES IN THE RATES OF PHOTOINACTIVATION OF THYMIDINE PHOSPHORYLASE. However, 5-iodo-2'-deoxyuridine at 5.0mM only enhanced the photoinactivation of enzyme by factors of 83 (pH 5) and 21 (pH 7.4). Neither 5-bromo-2'-deoxyuridine or 5-bromo-uracil was as potent in sensitizing the enzyme as the iodo analogs. Combinations of 5-iodouracil or 5-iodo-2'-deoxyuridine with thymine resulted in higher inactivation rates than the additive inactivation rates of individual compounds, whereas combinations of either iodo analog with thymidine resulted in lower inactivation rates. Increasing concentrations of phosphate or NaCl lessened the photoinactivation rate of thymidine phosphorylase alone and protected the enzyme from the sensitization caused by the different bases and nucleosides. No quantitative changes in the number of primary amino groups in thymidine phosphorylase was evident as a result of irradiation in the presence or absence of 5-iodouracil or 5-iodo-2'-deoxyuridine. Examination of the irradiated enzyme on Sephadex G-150 indicated that a larger protein species is formed and that 5-iodouracil promotes this process.", "contents": "Purification of thymidine phosphorylase from Escherichia coli and its photoinactivation in the presence of thymine, thymidine, and some halogenated analogs. Isoelectric focusing was used as the final step in the isolation of thymidine phosphorylase which was found to have an isoelectric point of 4.1. Analytical acrylamide gel electrophoresis showed the purified enzyme preparation contained one major protein band which stained for thymidine phosphorylase activity and usually a minor, faster migrating band devoid of activity. Inactivation of thymidine phosphorylase alone or in the presence of sensitizers by ultraviolet light, primarily at 253.7 nm, followed first order inactivation kinetics. The rate of inactivation of the enzyme was the same at pH 5 and 7.4 and the addition of various pyrimidine bases and nucleosides enhanced the inactivation rate at both pH values, but to a greater extent at pH 5. Linear plots of inactivation rates versus concentrations of thymidine or thymine were the same. At 7.8 mM thymidine or thymine, 11- and 4.4-fold increases in photoinactivation of thymidine phosphorylase were observed at pH 5 AND 7.4 RESPECTIVELY. Parabolic curves were obtained with increasing concentrations of either 5-iodo-2'-deoxyuridine or 5-iodouracil. 5-Iodouracil at 5.2 mM caused 212- (pH 5) and 100- (pH 7.4) FOLD INCREASES IN THE RATES OF PHOTOINACTIVATION OF THYMIDINE PHOSPHORYLASE. However, 5-iodo-2'-deoxyuridine at 5.0mM only enhanced the photoinactivation of enzyme by factors of 83 (pH 5) and 21 (pH 7.4). Neither 5-bromo-2'-deoxyuridine or 5-bromo-uracil was as potent in sensitizing the enzyme as the iodo analogs. Combinations of 5-iodouracil or 5-iodo-2'-deoxyuridine with thymine resulted in higher inactivation rates than the additive inactivation rates of individual compounds, whereas combinations of either iodo analog with thymidine resulted in lower inactivation rates. Increasing concentrations of phosphate or NaCl lessened the photoinactivation rate of thymidine phosphorylase alone and protected the enzyme from the sensitization caused by the different bases and nucleosides. No quantitative changes in the number of primary amino groups in thymidine phosphorylase was evident as a result of irradiation in the presence or absence of 5-iodouracil or 5-iodo-2'-deoxyuridine. Examination of the irradiated enzyme on Sephadex G-150 indicated that a larger protein species is formed and that 5-iodouracil promotes this process."}
{"id": "PMID:236299", "title": "Effect of phospholipase A on the structure and functions of membrane vesicles from Mycobacterium phlei.", "content": "The phospholipid composition of the electron transport particles and coupling factor-depleted electron transport particles of Mycobacterium phlei are the same, but they differ in contents. The accessibility of partially purified phospholipase A to these membrane phospholipids was found to be different. Treatment of membranes of Mycobacterium phlei with phospholipase A impairs the rate of oxidation as well as phosphorylation. The inhibition of phosphorylation can be reversed by washing the membranes with defatted bovine serum albumin. The reconstitution of membrane-bound coupling factor-latent ATPase activity to phospholipase A-treated depleted electron transport particles and their capacity to couple phosphorylation to oxidation of substrates remained unaffected after phospholipase A treatment. However, the pH gradient as measured by bromthymol blue was not restored after reconstitution of phospholipase A-treated depleted electron transport particles with membrane-bound coupling factor-latent ATPase. These findings show that the phosphorylation coupled to the oxidation of substrates can take place without a pronounced pH gradient in these membrane vesicles. The dye 1-anilino-8-naphthalene sulfonic acid (ANS) exhibited low levels of energized and nonenergized fluorescence in phospholipase A-treated membranes. This decrease in the level of ANS fluorescence in phospholipase A-treated membranes was found to be directly related to the amount of phospholipids cleaved. The decrease in the energy-dependent ANS response in phospholipase A-treated electron transport particles, as compared with untreated electron transport particles, was shown to be a result of a change in the apparent K-d of the dye-membrane complex, and of a decrease in the number of irreversible or slowly reversible binding sites, with no change in the relative quantum efficiency of the dye. The decrease in ANS fluorescence in phospholipase A-treated particles appears to be due to a decrease in the hydrophobicity of the membranes.", "contents": "Effect of phospholipase A on the structure and functions of membrane vesicles from Mycobacterium phlei. The phospholipid composition of the electron transport particles and coupling factor-depleted electron transport particles of Mycobacterium phlei are the same, but they differ in contents. The accessibility of partially purified phospholipase A to these membrane phospholipids was found to be different. Treatment of membranes of Mycobacterium phlei with phospholipase A impairs the rate of oxidation as well as phosphorylation. The inhibition of phosphorylation can be reversed by washing the membranes with defatted bovine serum albumin. The reconstitution of membrane-bound coupling factor-latent ATPase activity to phospholipase A-treated depleted electron transport particles and their capacity to couple phosphorylation to oxidation of substrates remained unaffected after phospholipase A treatment. However, the pH gradient as measured by bromthymol blue was not restored after reconstitution of phospholipase A-treated depleted electron transport particles with membrane-bound coupling factor-latent ATPase. These findings show that the phosphorylation coupled to the oxidation of substrates can take place without a pronounced pH gradient in these membrane vesicles. The dye 1-anilino-8-naphthalene sulfonic acid (ANS) exhibited low levels of energized and nonenergized fluorescence in phospholipase A-treated membranes. This decrease in the level of ANS fluorescence in phospholipase A-treated membranes was found to be directly related to the amount of phospholipids cleaved. The decrease in the energy-dependent ANS response in phospholipase A-treated electron transport particles, as compared with untreated electron transport particles, was shown to be a result of a change in the apparent K-d of the dye-membrane complex, and of a decrease in the number of irreversible or slowly reversible binding sites, with no change in the relative quantum efficiency of the dye. The decrease in ANS fluorescence in phospholipase A-treated particles appears to be due to a decrease in the hydrophobicity of the membranes."}
{"id": "PMID:236300", "title": "Tryptophan fluorescence lifetimes in lysozyme.", "content": "Tryptophan fluorescence lifetimes at pH 2 and pH 8 have been obtained for lysozyme and for lysozyme derivatives in which tryptophan-62 or tryptophan-108 or both are nonfluorescent. The lifetimes range from about 0.5 ns to 2.8 ns for the various emitting tryptophans. The tryptophan lifetimes appear to increase with exposure of tryptophan to solvent, but intramolecular contacts, probably with cystine residues, can considerably shorten the lifetime. Intertryptophanyl interactions can also affect fluorescence lifetimes. The trytophan-108 lifetime in lysozyme is shorter than in the derivative in which tryptophan-62 is oxidized; this is ascribed to energy transfer from tryptophan-108 to tryptophan-62. From the lifetime results the relative intensities emitted by specific tryptophans can be estimated, and these values also support the existence of intertryptophanyl energy transfer. The emission intensity from tryptophan-62 is greater in the presence of tryptophan-108, and the emission intensity of tryptophan-108 appears to be greater in the absence of tryptophan-62. Conformational effects accompanying chemical modification of tryptophan cannot be completely ruled out, however. The tryptophan-62 lifetime at pH 8 in lysozyme is shorter than in the derivatives, which might indicate a subtle conformational effect. Studies with tri-(N-acetyl-glucosamine)-protein complexes indicate that both the tryptophan lifetimes and the number of emitting tryptophans may be changing upon complexation. The results illustrate the usefulness and the limitations of lifetime measurements in understanding protein fluorescence.", "contents": "Tryptophan fluorescence lifetimes in lysozyme. Tryptophan fluorescence lifetimes at pH 2 and pH 8 have been obtained for lysozyme and for lysozyme derivatives in which tryptophan-62 or tryptophan-108 or both are nonfluorescent. The lifetimes range from about 0.5 ns to 2.8 ns for the various emitting tryptophans. The tryptophan lifetimes appear to increase with exposure of tryptophan to solvent, but intramolecular contacts, probably with cystine residues, can considerably shorten the lifetime. Intertryptophanyl interactions can also affect fluorescence lifetimes. The trytophan-108 lifetime in lysozyme is shorter than in the derivative in which tryptophan-62 is oxidized; this is ascribed to energy transfer from tryptophan-108 to tryptophan-62. From the lifetime results the relative intensities emitted by specific tryptophans can be estimated, and these values also support the existence of intertryptophanyl energy transfer. The emission intensity from tryptophan-62 is greater in the presence of tryptophan-108, and the emission intensity of tryptophan-108 appears to be greater in the absence of tryptophan-62. Conformational effects accompanying chemical modification of tryptophan cannot be completely ruled out, however. The tryptophan-62 lifetime at pH 8 in lysozyme is shorter than in the derivatives, which might indicate a subtle conformational effect. Studies with tri-(N-acetyl-glucosamine)-protein complexes indicate that both the tryptophan lifetimes and the number of emitting tryptophans may be changing upon complexation. The results illustrate the usefulness and the limitations of lifetime measurements in understanding protein fluorescence."}
{"id": "PMID:236301", "title": "Purification and characterization of N-methylalanine dehydrogenase.", "content": "Cell free extracts of Pseudomonas MS previously have been shown to carry out the synthesis of a novel amino acid, N-methylalanine (Kung, H.F., and Wagner, C. (1970) Biochim. Biophys. Acta 201, 513-516). An enzyme has been isolated from this organism which is responsible for the synthesis of N-methylalanine. The stoichiometry of the reaction catalyzed by this enzyme leads to the following formulation: Methylamine + pyruvate + NADPH + H-+ yields N-methylalanine + NADP-+ + H2O. This enzyme has been physically separated from alanine dehydrogenase, which is also present in these extracts. This new enzyme has been named N-methylalanine dehydrogenase. It has been purified to near homogeneity as judged by disc gel electrophoresis. Gel filtration chromatography showed that N-methylalanine dehydrogenase has an apparent molecular weight of 77,000, while electrophoresis in sodium dodecyl sulfate gave rise to a single band with a molecular weight of approximately 36,500. The enzyme is optimally active in the pH range between 8.2 and 8.6. The apparent K-m values for pyruvate, NADPH, and methylamine, respectively, are 1-5 times 10 minus 2 M, 3-5 times 10 minus 5 M, and 7.5 times 10 minus 2 M.", "contents": "Purification and characterization of N-methylalanine dehydrogenase. Cell free extracts of Pseudomonas MS previously have been shown to carry out the synthesis of a novel amino acid, N-methylalanine (Kung, H.F., and Wagner, C. (1970) Biochim. Biophys. Acta 201, 513-516). An enzyme has been isolated from this organism which is responsible for the synthesis of N-methylalanine. The stoichiometry of the reaction catalyzed by this enzyme leads to the following formulation: Methylamine + pyruvate + NADPH + H-+ yields N-methylalanine + NADP-+ + H2O. This enzyme has been physically separated from alanine dehydrogenase, which is also present in these extracts. This new enzyme has been named N-methylalanine dehydrogenase. It has been purified to near homogeneity as judged by disc gel electrophoresis. Gel filtration chromatography showed that N-methylalanine dehydrogenase has an apparent molecular weight of 77,000, while electrophoresis in sodium dodecyl sulfate gave rise to a single band with a molecular weight of approximately 36,500. The enzyme is optimally active in the pH range between 8.2 and 8.6. The apparent K-m values for pyruvate, NADPH, and methylamine, respectively, are 1-5 times 10 minus 2 M, 3-5 times 10 minus 5 M, and 7.5 times 10 minus 2 M."}
{"id": "PMID:236302", "title": "Specific limited cleavage of bihelical deoxyribonucleic acid by wheat seedling nuclease.", "content": "Wheat seedling nuclease catalyzes the hydrolysis of intact, bihelical viral DNA or high molecular weight, native Escherichia coli DNA to produce limit polymers which are resistant to further hydrolysis by additional enzyme. These limit products are double-stranded polymers free of single strand interruptions and are terminated at their 5' ends with equal amounts of either deoxycytidylate or deoxyguanylate residues. The average size of the duplex limit products, as determined by (a) alkaline and neutral sucrose gradient sedimentation, (b) viscometric determination of molecular weight, and (c) 5'-end labeling, varies from 2 to 4 times 10-6 depending on the source of the DNA. The involvement of regions rich in adenine-thymine base pairs at the sites of cleavage of the DNA molecule is suggested by the following experimental results: (a) the copolymeric duplex, poly(dA-dt) is hydrolyzed at a rate comparable to that found for denatured calf thymus DNA, a rate which is several orders of magnitude faster than that at which native calf thymus DNA is hydrolyzed; (b) lambda DNA, which contains an adenine-thymine-rich region near its center, is rapidly cleaved to yield two fragments of similar size; (c) the rate of hydrolysis of native DNA is increased approximately 14-fold by increasing the reaction temperature from 20 degrees to 30 degrees.", "contents": "Specific limited cleavage of bihelical deoxyribonucleic acid by wheat seedling nuclease. Wheat seedling nuclease catalyzes the hydrolysis of intact, bihelical viral DNA or high molecular weight, native Escherichia coli DNA to produce limit polymers which are resistant to further hydrolysis by additional enzyme. These limit products are double-stranded polymers free of single strand interruptions and are terminated at their 5' ends with equal amounts of either deoxycytidylate or deoxyguanylate residues. The average size of the duplex limit products, as determined by (a) alkaline and neutral sucrose gradient sedimentation, (b) viscometric determination of molecular weight, and (c) 5'-end labeling, varies from 2 to 4 times 10-6 depending on the source of the DNA. The involvement of regions rich in adenine-thymine base pairs at the sites of cleavage of the DNA molecule is suggested by the following experimental results: (a) the copolymeric duplex, poly(dA-dt) is hydrolyzed at a rate comparable to that found for denatured calf thymus DNA, a rate which is several orders of magnitude faster than that at which native calf thymus DNA is hydrolyzed; (b) lambda DNA, which contains an adenine-thymine-rich region near its center, is rapidly cleaved to yield two fragments of similar size; (c) the rate of hydrolysis of native DNA is increased approximately 14-fold by increasing the reaction temperature from 20 degrees to 30 degrees."}
{"id": "PMID:236303", "title": "The structure of annelid and mollusc hemoglobins.", "content": "The polypeptide chain composition and the chemical properties of several annelid hemoglobins and chlorocruorins are presented. In agreement with earlier studies on the hemoglobin from Arenicola cristata (Waxman, L. (1971) J. Biol. Chem. 246, 7318-7327), nearly all of the pigments which have been examined consist of one or more different disulfide-linked polypeptide chains of 13,000 to 16,000 daltons, and the heme-protein stoichiometry suggests that more than one polypeptide is associated with each heme. Except for the prosthetic group, there is no outstanding chemical difference between the chlorocruorins and the hemoglobins, nor is ther any apparent differnce between those hemoglobins which show cooperative oxygen binding properties and those which do not. The results suggest that all these hemoglobins have similar structures. On the other hand, the polypeptide chains of mollusc hemoglobins have molecular weights of greater than 220,000. Each polypeptide binds many heme groups. Thus, annelids use small polypeptide chains while molluscs use giant polypeptides to carry O2.", "contents": "The structure of annelid and mollusc hemoglobins. The polypeptide chain composition and the chemical properties of several annelid hemoglobins and chlorocruorins are presented. In agreement with earlier studies on the hemoglobin from Arenicola cristata (Waxman, L. (1971) J. Biol. Chem. 246, 7318-7327), nearly all of the pigments which have been examined consist of one or more different disulfide-linked polypeptide chains of 13,000 to 16,000 daltons, and the heme-protein stoichiometry suggests that more than one polypeptide is associated with each heme. Except for the prosthetic group, there is no outstanding chemical difference between the chlorocruorins and the hemoglobins, nor is ther any apparent differnce between those hemoglobins which show cooperative oxygen binding properties and those which do not. The results suggest that all these hemoglobins have similar structures. On the other hand, the polypeptide chains of mollusc hemoglobins have molecular weights of greater than 220,000. Each polypeptide binds many heme groups. Thus, annelids use small polypeptide chains while molluscs use giant polypeptides to carry O2."}
{"id": "PMID:236304", "title": "Cathodal proteins from primitive (embryonic) red cells of amphibia. Isolation and characterization.", "content": "A group of abundant (15% of the soluble protein) nonhemoglobin proteins was isolated from the primitive (embryonic) red cells found in tadpoles, using the cationic properties of the proteins at pH 8.6 to separate them from hemoglobin and other red cell proteins. The cathodal proteins (CP) were resolved into five components, and the two most predominant proteins were separated and characterized. Purified CP-1b and CP-2 had an amino acid composition similar to that of unfractionated cathodal proteins and to each other, except for small variations in the lysine and half-cystine content. The molecular weight of the purified CP-1b and CP-2 was 13 to 14,000, determined by gel filtration chromatography and electrophoresis in the presence of sodium dodecyl sulfate. Cathodal proteins were immunologically related although there were quantitative differences in reactivity. The concentration of cathodal proteins in primitive (embryonic) red cells was 100 times that in definitive (adult) red cells coincided with the replacement of primitive red cells. The synthesis of the cathodal proteins appeared to continue throughout the life of the primitive red cells; when hemoglobin synthesis declined in primitive red cells, approximately half of the protein synthesized by the cells was cathodal protein. Although the function of the cathodal proteins is as yet unknown, the data suggest that the cathodal proteins are a unique characteristic of erythroid differentiation in early development.", "contents": "Cathodal proteins from primitive (embryonic) red cells of amphibia. Isolation and characterization. A group of abundant (15% of the soluble protein) nonhemoglobin proteins was isolated from the primitive (embryonic) red cells found in tadpoles, using the cationic properties of the proteins at pH 8.6 to separate them from hemoglobin and other red cell proteins. The cathodal proteins (CP) were resolved into five components, and the two most predominant proteins were separated and characterized. Purified CP-1b and CP-2 had an amino acid composition similar to that of unfractionated cathodal proteins and to each other, except for small variations in the lysine and half-cystine content. The molecular weight of the purified CP-1b and CP-2 was 13 to 14,000, determined by gel filtration chromatography and electrophoresis in the presence of sodium dodecyl sulfate. Cathodal proteins were immunologically related although there were quantitative differences in reactivity. The concentration of cathodal proteins in primitive (embryonic) red cells was 100 times that in definitive (adult) red cells coincided with the replacement of primitive red cells. The synthesis of the cathodal proteins appeared to continue throughout the life of the primitive red cells; when hemoglobin synthesis declined in primitive red cells, approximately half of the protein synthesized by the cells was cathodal protein. Although the function of the cathodal proteins is as yet unknown, the data suggest that the cathodal proteins are a unique characteristic of erythroid differentiation in early development."}
{"id": "PMID:236305", "title": "Metabolism of resorcinylic compounds by bacteria. Purification and properties of acetylpyruvate hydrolase from Pseudomonas putida 01.", "content": "Acetylpyruvate hydrolase, the terminal inducible enzyme of the pathway of orcinol catabolism in Pseudomonas putida, catalyzes the quantitative conversion of acetylpyruvate into acetate and pyruvate. The enzyme has been purified approximately 40-fold from extracts of Ps. putida grown on orcinol. Disc gel electrophoresis of the preparations show one major and one minor band of protein. The molecular weight of the enzyme is approximately 38,000 by sodium dodecyl sulfate electrophoresis. Acetylpyruvate is the only known substrate for the enzyme; maleylpyruvate, fumarylpyruvate, acetoacetate, oxalacetate, and acetylacetone are not hydrolyzed by acetylpyruvate hydrolase. Several divalent cations, includ-Mg2+, Mn2+, Co2+, Ca2+, and Zn2+, enhanced hydrolytic activity, but Cu2+ was inhibitory. The enzyme shows a sharp pH optimum at 7.4. Acetylpyruvate hydrolase has an apparent K-m of 0.1 mM for acetylpyruvate with a molecular activity of 36 min minus 1 at 25 degrees. Pyruvate, oxalacetate, and oxalate are competitive inhibitors of acetylpyruvate hydrolysis by the enzyme with K-i values of 6.0, 4.5, and 0.45 mM, respectively.", "contents": "Metabolism of resorcinylic compounds by bacteria. Purification and properties of acetylpyruvate hydrolase from Pseudomonas putida 01. Acetylpyruvate hydrolase, the terminal inducible enzyme of the pathway of orcinol catabolism in Pseudomonas putida, catalyzes the quantitative conversion of acetylpyruvate into acetate and pyruvate. The enzyme has been purified approximately 40-fold from extracts of Ps. putida grown on orcinol. Disc gel electrophoresis of the preparations show one major and one minor band of protein. The molecular weight of the enzyme is approximately 38,000 by sodium dodecyl sulfate electrophoresis. Acetylpyruvate is the only known substrate for the enzyme; maleylpyruvate, fumarylpyruvate, acetoacetate, oxalacetate, and acetylacetone are not hydrolyzed by acetylpyruvate hydrolase. Several divalent cations, includ-Mg2+, Mn2+, Co2+, Ca2+, and Zn2+, enhanced hydrolytic activity, but Cu2+ was inhibitory. The enzyme shows a sharp pH optimum at 7.4. Acetylpyruvate hydrolase has an apparent K-m of 0.1 mM for acetylpyruvate with a molecular activity of 36 min minus 1 at 25 degrees. Pyruvate, oxalacetate, and oxalate are competitive inhibitors of acetylpyruvate hydrolysis by the enzyme with K-i values of 6.0, 4.5, and 0.45 mM, respectively."}
{"id": "PMID:236306", "title": "Oxidation-reduction potentials of human fetal hemoglobin and gamma chains. Effects of blocking sulfhydryl groups.", "content": "The oxidation-reduction equilibrium of the gamma chains of human fetal hemoglobin (Hb F) has been studied and compared with that of the alpha and beta chains of human adult hemoglobin (Hb A). The effects of the sulfhydryl (--SH) reagents, iodoacetate, iodoacetamide, and p-mercuribenzoate (PMB), on the three kinds of chains and on Hb F have been compared. The midpoint potentials (E-m) of all three sorts of chains are lower than those of tetrameric hemoglobin A or F. The E-m values of alpha chains are the lowest, E-m = 0.049 volt at 6 degrees, and are unaffected by pH change or by PMB treatment, at least from pH 6 to 8. The E-m values of beta-SH chains are higher; E-m = 0.102 volt at pH 7, decreasing to 0.050 volt at pH 8, both at 6 degrees. These results agree with those of Banerjee and Cassoly ((1969) J. Mol. Biol. 42, 337-349). They reported no effect of PMB on beta chains, but we find that 2 eq of PMB/chain raise E--M to 0.139 volt at pH 7 at 6 degrees, chiefly as the result of reaction at beta-93, not at beta-112. Carboxymethylation at beta-93 has an insignificant effect compared with that of PMB. The oxidation-reduction potential of gamma chains is similar to that of beta chains. E-m = 0.098 volt at pH 7 at 6 degrees, decreasing to 0.064 at pH 8 and 0.010 at pH 9. The effects of --SH reagents, reacting at position gamma-93 (the only --SH group present in gamma chains), are essentially the same as those seen with beta chains. The oxidation-reduction potential of Hb F is almost identical with that of Hb A, except for being 0.008 volt lower at pH 6 at 6 degrees. This agrees with the results reported by Flohe and Uehleke ((1966) Life Sci. 5, 1041-1045). PMB or iodoacetamide treatment lowers E-m by 0.02 to 0.03 volt, depending on the pH, from 6 to 9, in much the same way as previously reported for Hb A(Brunori, M., Taylor, J.F., Antonini, E., Wyman, J., and Rossi-Fanelli, A. (1967) J. Biol. Chem. 242, 2295-2300). The \"residual oxidation Bohr effect\" noted in Hb F can be attributed to the oxidation Bohr effect of the gamma chains. The apparent pK of the heme-linked water molecule was found at 25 degrees to be, for Hb F, 8.1; for gamma-SH chains, 7.85; for gamma-PMB chains, 8.35; and for gamma chains treated with iodoacetate, 7.80. Sedimentation coefficients, s-20, w, at a protein concentration of 5 mg/ml, were found to be, for fetal hemoglobin 4.09, for iodoacetamide-treated fetal hemoglobin 4.04, for PMB-treated fetal hemoglobin 3.41, for fetal gamma-SH chains 4.25, and for fetal gamma-PMB chains 3.08.", "contents": "Oxidation-reduction potentials of human fetal hemoglobin and gamma chains. Effects of blocking sulfhydryl groups. The oxidation-reduction equilibrium of the gamma chains of human fetal hemoglobin (Hb F) has been studied and compared with that of the alpha and beta chains of human adult hemoglobin (Hb A). The effects of the sulfhydryl (--SH) reagents, iodoacetate, iodoacetamide, and p-mercuribenzoate (PMB), on the three kinds of chains and on Hb F have been compared. The midpoint potentials (E-m) of all three sorts of chains are lower than those of tetrameric hemoglobin A or F. The E-m values of alpha chains are the lowest, E-m = 0.049 volt at 6 degrees, and are unaffected by pH change or by PMB treatment, at least from pH 6 to 8. The E-m values of beta-SH chains are higher; E-m = 0.102 volt at pH 7, decreasing to 0.050 volt at pH 8, both at 6 degrees. These results agree with those of Banerjee and Cassoly ((1969) J. Mol. Biol. 42, 337-349). They reported no effect of PMB on beta chains, but we find that 2 eq of PMB/chain raise E--M to 0.139 volt at pH 7 at 6 degrees, chiefly as the result of reaction at beta-93, not at beta-112. Carboxymethylation at beta-93 has an insignificant effect compared with that of PMB. The oxidation-reduction potential of gamma chains is similar to that of beta chains. E-m = 0.098 volt at pH 7 at 6 degrees, decreasing to 0.064 at pH 8 and 0.010 at pH 9. The effects of --SH reagents, reacting at position gamma-93 (the only --SH group present in gamma chains), are essentially the same as those seen with beta chains. The oxidation-reduction potential of Hb F is almost identical with that of Hb A, except for being 0.008 volt lower at pH 6 at 6 degrees. This agrees with the results reported by Flohe and Uehleke ((1966) Life Sci. 5, 1041-1045). PMB or iodoacetamide treatment lowers E-m by 0.02 to 0.03 volt, depending on the pH, from 6 to 9, in much the same way as previously reported for Hb A(Brunori, M., Taylor, J.F., Antonini, E., Wyman, J., and Rossi-Fanelli, A. (1967) J. Biol. Chem. 242, 2295-2300). The \"residual oxidation Bohr effect\" noted in Hb F can be attributed to the oxidation Bohr effect of the gamma chains. The apparent pK of the heme-linked water molecule was found at 25 degrees to be, for Hb F, 8.1; for gamma-SH chains, 7.85; for gamma-PMB chains, 8.35; and for gamma chains treated with iodoacetate, 7.80. Sedimentation coefficients, s-20, w, at a protein concentration of 5 mg/ml, were found to be, for fetal hemoglobin 4.09, for iodoacetamide-treated fetal hemoglobin 4.04, for PMB-treated fetal hemoglobin 3.41, for fetal gamma-SH chains 4.25, and for fetal gamma-PMB chains 3.08."}
{"id": "PMID:236307", "title": "Macromolecular characterization of muscle membranes. Endogenous membrane kinase and phosphorylated protein substrate from normal and denervated muscle.", "content": "Light density membranes derived from the \"microsomal\" fraction of rat skeletal muscle contained an endogenous protein kinase which catalyzed the phosphorylation of an endogenous membrane substrate. No other membrane fraction contained any significant protein kinase activity. The optimal specific activity of the enzyme in these membranes was 350 pmol/mg/min. The endogenous muscle membrane protein kinase required magnesium, was stimulated by micromolar concentrations of calcium, had a pH optimum between 7.0 and 7.5, and demonstrated a K-m for ATP of 2.6 times 10 minus 5 M. The enzyme was markedly heat labile and demonstrated a linear Arrhenius plot with an apparent energy of activation of 12,100 cal/mol. There was no stimulation by cyclic nucleotides; and neither monovalent cations nor various neurotransmitters exerted any effect. It is presently unclear where the membranes exhibiting protein phosphorylation are localized within the muscle fiber. Enzyme markers suggest that these membranes are not derived from sarcolemma or sarcoplasmic reticulum but may originate in transverse tubules. The membrane phosphorylation was largely confined to a polypeptide with an apparent molecular weight of 28,000. Phosphorylation could also be detected in a lower molecular weight substrate as well as two polypeptides with apparent molecular weights of 95,000 and 56,000. The M-r-28,000 endogenous protein kinase substrate was isolated by preparative gel electrophoresis in sodium dodecyl sulfate. High voltage electrophoresis of a partial acid hydrolysate of the phosphorylated M-r-28,000 substrate identified the phosphate bond to be that of phosphoserine. The amino acid composition of the substrate was neither strongly acidic nor basic. It had a high content of glycine, glutamic acid, serine, and lysine. Hydrophobic residues constituted only 45% of the total composition. Following muscle denervation for 10 days, there was a significant decrease in the amount of the M-r-28,000 polypeptide as well as the extent of phosphorylation.", "contents": "Macromolecular characterization of muscle membranes. Endogenous membrane kinase and phosphorylated protein substrate from normal and denervated muscle. Light density membranes derived from the \"microsomal\" fraction of rat skeletal muscle contained an endogenous protein kinase which catalyzed the phosphorylation of an endogenous membrane substrate. No other membrane fraction contained any significant protein kinase activity. The optimal specific activity of the enzyme in these membranes was 350 pmol/mg/min. The endogenous muscle membrane protein kinase required magnesium, was stimulated by micromolar concentrations of calcium, had a pH optimum between 7.0 and 7.5, and demonstrated a K-m for ATP of 2.6 times 10 minus 5 M. The enzyme was markedly heat labile and demonstrated a linear Arrhenius plot with an apparent energy of activation of 12,100 cal/mol. There was no stimulation by cyclic nucleotides; and neither monovalent cations nor various neurotransmitters exerted any effect. It is presently unclear where the membranes exhibiting protein phosphorylation are localized within the muscle fiber. Enzyme markers suggest that these membranes are not derived from sarcolemma or sarcoplasmic reticulum but may originate in transverse tubules. The membrane phosphorylation was largely confined to a polypeptide with an apparent molecular weight of 28,000. Phosphorylation could also be detected in a lower molecular weight substrate as well as two polypeptides with apparent molecular weights of 95,000 and 56,000. The M-r-28,000 endogenous protein kinase substrate was isolated by preparative gel electrophoresis in sodium dodecyl sulfate. High voltage electrophoresis of a partial acid hydrolysate of the phosphorylated M-r-28,000 substrate identified the phosphate bond to be that of phosphoserine. The amino acid composition of the substrate was neither strongly acidic nor basic. It had a high content of glycine, glutamic acid, serine, and lysine. Hydrophobic residues constituted only 45% of the total composition. Following muscle denervation for 10 days, there was a significant decrease in the amount of the M-r-28,000 polypeptide as well as the extent of phosphorylation."}
{"id": "PMID:236308", "title": "High resolution two-dimensional electrophoresis of proteins.", "content": "A technique has been developed for the separation of proteins by two-dimensional polyacrylamide gel electrophoresis. Due to its resolution and sensitivity, this technique is a powerful tool for the analysis and detection of proteins from complex biological sources. Proteins are separated according to isoelectric point by isoelectric focusing in the first dimension, and according to molecular weight by sodium dodecyl sulfate electrophoresis in the second dimension. Since these two parameters are unrelated, it is possible to obtain an almost uniform distribution of protein spots across a two-diminsional gel. This technique has resolved 1100 different components from Escherichia coli and should be capable of resolving a maximum of 5000 proteins. A protein containing as little as one disintegration per min of either 14C or 35S can be detected by autoradiography. A protein which constitutes 10 minus 4 to 10 minus 5% of the total protein can be detected and quantified by autoradiography. The reproducibility of the separation is sufficient to permit each spot on one separation to be matched with a spot on a different separation. This technique provides a method for estimation (at the described sensitivities) of the number of proteins made by any biological system. This system can resolve proteins differing in a single charge and consequently can be used in the analysis of in vivo modifications resulting in a change in charge. Proteins whose charge is changed by missense mutations can be identified. A detailed description of the methods as well as the characteristics of this system are presented.", "contents": "High resolution two-dimensional electrophoresis of proteins. A technique has been developed for the separation of proteins by two-dimensional polyacrylamide gel electrophoresis. Due to its resolution and sensitivity, this technique is a powerful tool for the analysis and detection of proteins from complex biological sources. Proteins are separated according to isoelectric point by isoelectric focusing in the first dimension, and according to molecular weight by sodium dodecyl sulfate electrophoresis in the second dimension. Since these two parameters are unrelated, it is possible to obtain an almost uniform distribution of protein spots across a two-diminsional gel. This technique has resolved 1100 different components from Escherichia coli and should be capable of resolving a maximum of 5000 proteins. A protein containing as little as one disintegration per min of either 14C or 35S can be detected by autoradiography. A protein which constitutes 10 minus 4 to 10 minus 5% of the total protein can be detected and quantified by autoradiography. The reproducibility of the separation is sufficient to permit each spot on one separation to be matched with a spot on a different separation. This technique provides a method for estimation (at the described sensitivities) of the number of proteins made by any biological system. This system can resolve proteins differing in a single charge and consequently can be used in the analysis of in vivo modifications resulting in a change in charge. Proteins whose charge is changed by missense mutations can be identified. A detailed description of the methods as well as the characteristics of this system are presented."}
{"id": "PMID:236309", "title": "A deoxyribonuclease of Diplococcus pneumoniae specific for methylated DNA.", "content": "A deoxyribonuclease specific for methylated DNA was isolated from Diplococcus pneumoniae. The enzyme, an endonuclease, degrades DNA for Escherichia coli to fragments of average molecular weight about half a million; it forms discrete fragments from phage lambda DNA. Methyl-deficient E. coli DNA is not attacked, neither is DNA from Micrococcus radiodurans, which contains no methylated adenine or cytosine. Nor is DNA from D. pneumoniae or phage T7 attacked. However, DNA from M. radiodurans, D. pneumoniae, and T7 is attacked after methylation with and E. coli extract. Methylated T7 DNA is degraded to discrete fragments. Although the genetic transforming activity of normal DNA from D. pneumoniae is not affected by the enzyme, transforming activity of methylated DNA is destroyed. The enzyme is designated endonuclease R Dpn I. Under certain conditions another enzyme of complementary specificity can be isolated. This enzyme, designated endonuclease R Dpn II, produces a similar pattern of fragments from the DNA of T7 without prior methylation of the DNA. It also degrades normal DNA for D. pneumoniae. It is suggested that this pair of enzymes plays a role in some unknown control process, which would involve a large fraction of the specific base sequences that are methylated in E. coli DNA and are present but not methylated in DNA from other sources.", "contents": "A deoxyribonuclease of Diplococcus pneumoniae specific for methylated DNA. A deoxyribonuclease specific for methylated DNA was isolated from Diplococcus pneumoniae. The enzyme, an endonuclease, degrades DNA for Escherichia coli to fragments of average molecular weight about half a million; it forms discrete fragments from phage lambda DNA. Methyl-deficient E. coli DNA is not attacked, neither is DNA from Micrococcus radiodurans, which contains no methylated adenine or cytosine. Nor is DNA from D. pneumoniae or phage T7 attacked. However, DNA from M. radiodurans, D. pneumoniae, and T7 is attacked after methylation with and E. coli extract. Methylated T7 DNA is degraded to discrete fragments. Although the genetic transforming activity of normal DNA from D. pneumoniae is not affected by the enzyme, transforming activity of methylated DNA is destroyed. The enzyme is designated endonuclease R Dpn I. Under certain conditions another enzyme of complementary specificity can be isolated. This enzyme, designated endonuclease R Dpn II, produces a similar pattern of fragments from the DNA of T7 without prior methylation of the DNA. It also degrades normal DNA for D. pneumoniae. It is suggested that this pair of enzymes plays a role in some unknown control process, which would involve a large fraction of the specific base sequences that are methylated in E. coli DNA and are present but not methylated in DNA from other sources."}
{"id": "PMID:236310", "title": "Thyroid hormone receptors. Binding characteristics and lack of hormonal dependency for nuclear localization.", "content": "Thyroid hormones have diverse effects on growth and metabolism. Specific \"receptor\" proteins which bind triiodothyronine and other biologically active analogs and which may be involved in thyroid hormone action have been recently found in nuclei of responsive tissues. This report presents studies of these receptors in rat liver nuclei. Confirming previous reports, a Scatchard analysis of the binding data suggests the reaction, triiodothyronine + specific receptor in equilibrium with triiodothyronine-receptor complex, with an apparent equilibrium dissociation constant (Kd) at 22 degrees of about 190 pM and a capacity of about 1 pmol of triiodothyronine-binding sites per mg of DNA. The kinetics of the binding were also examined. Triiodothyronine-receptor complex formation is second order and dissociation is first order. The apparent association (k+1) and dissociation (k minus 1) rate constants at 22 degrees are, respectively, 4.7 times 10-7 m-minus 1 min-minus 1 and 7.6 times 10-minus 3 min-minus 1. The apparent Kd, estimated from the ratio of the rate constants (k minus 1:k+1), was about 150 pM, similar to that determined from the equilibrium data. These data support the expression written above for the interaction of thyroid hormone with its receptor. Additional kinetic experiments indicate that some of the triiodothyronine binding by cell-free nuclei is to sites previously occupied by hormone in the intact animal, providing further evidence that the intact cell and cell-free reactions are the same. It was previously found that nuclear-bound triiodothyronine is localized in chromatin. We found that isolated chromatin retains specific binding activity similar to that of isolated nuclei. Thus, binding may not require cytoplasmic, nucleoplasmic, or nuclear membrane factors. These findings may imply that chromatin localization of the receptor does not depend on the hormone. This idea is supported by an earlier finding that binding activity is present in nuclei from thyroidectomized animals. However, many stimuli such as steroid hormones, bacterial inducers, and cyclic adenosine 3':5'-monophosphate in bacteria influence regulatory proteins at the gene level by promoting the protein's addition to or removal from chromatin. Thus, we studied the effect of thyroid hormone on the nuclear content of receptors under assay conditions of receptor stability and reversible binding. Receptor levels in hypothyroid animals are identical with those in euthyroid animals. These data suggest that the hormone does not influence the nuclear localization of receptors. Thus, the basis for thyroid hormone action may be to regulate the activity of receptors resident in chromatin rather than to promote receptor addition to or removal from chromatin.", "contents": "Thyroid hormone receptors. Binding characteristics and lack of hormonal dependency for nuclear localization. Thyroid hormones have diverse effects on growth and metabolism. Specific \"receptor\" proteins which bind triiodothyronine and other biologically active analogs and which may be involved in thyroid hormone action have been recently found in nuclei of responsive tissues. This report presents studies of these receptors in rat liver nuclei. Confirming previous reports, a Scatchard analysis of the binding data suggests the reaction, triiodothyronine + specific receptor in equilibrium with triiodothyronine-receptor complex, with an apparent equilibrium dissociation constant (Kd) at 22 degrees of about 190 pM and a capacity of about 1 pmol of triiodothyronine-binding sites per mg of DNA. The kinetics of the binding were also examined. Triiodothyronine-receptor complex formation is second order and dissociation is first order. The apparent association (k+1) and dissociation (k minus 1) rate constants at 22 degrees are, respectively, 4.7 times 10-7 m-minus 1 min-minus 1 and 7.6 times 10-minus 3 min-minus 1. The apparent Kd, estimated from the ratio of the rate constants (k minus 1:k+1), was about 150 pM, similar to that determined from the equilibrium data. These data support the expression written above for the interaction of thyroid hormone with its receptor. Additional kinetic experiments indicate that some of the triiodothyronine binding by cell-free nuclei is to sites previously occupied by hormone in the intact animal, providing further evidence that the intact cell and cell-free reactions are the same. It was previously found that nuclear-bound triiodothyronine is localized in chromatin. We found that isolated chromatin retains specific binding activity similar to that of isolated nuclei. Thus, binding may not require cytoplasmic, nucleoplasmic, or nuclear membrane factors. These findings may imply that chromatin localization of the receptor does not depend on the hormone. This idea is supported by an earlier finding that binding activity is present in nuclei from thyroidectomized animals. However, many stimuli such as steroid hormones, bacterial inducers, and cyclic adenosine 3':5'-monophosphate in bacteria influence regulatory proteins at the gene level by promoting the protein's addition to or removal from chromatin. Thus, we studied the effect of thyroid hormone on the nuclear content of receptors under assay conditions of receptor stability and reversible binding. Receptor levels in hypothyroid animals are identical with those in euthyroid animals. These data suggest that the hormone does not influence the nuclear localization of receptors. Thus, the basis for thyroid hormone action may be to regulate the activity of receptors resident in chromatin rather than to promote receptor addition to or removal from chromatin."}
{"id": "PMID:236311", "title": "Multispecific aspartate and aromatic amino acid aminotransferases in Escherichia coli.", "content": "Two aminotransferases from Escherichia coli were purified to homogeneity by the criterion of gel electrophoresis. The first (enzyme A) is active on L-aspartic acid, L-tyrosine, L-phenylalanine, and L-tryptophan; the second (enzyme B) is active on the aromatic amiono acids. Enzyme A is identical in substrate specificity with transaminase A and is mainly an aspartate aminotransferase; enzyme B has never been described before and is an aromatic amino acid aminotransferase. The two enzymes are different in the Vmax and Km values with their common substrates and pyridoxal phosphate, in heat stability (enzyme A being heat-stable and enzyme B being heat-labile at 55 degrees) and in pH optima with the amino acid substrates. They are similar in their amino acid composition, each enzyme appears to consist of two subunits, and enzyme B may be converted to enzyme A by controlled proteolysis with subtilsin. The conversion was detected by the generation of new aspartate aminotransferase activity from enzyme B and was further verified by identification by acrylamide gel electrophoresis of the newly formed enzyme A. The two enzymes appear to be products of two genes different in a small, probably terminal, nucleotide sequence.", "contents": "Multispecific aspartate and aromatic amino acid aminotransferases in Escherichia coli. Two aminotransferases from Escherichia coli were purified to homogeneity by the criterion of gel electrophoresis. The first (enzyme A) is active on L-aspartic acid, L-tyrosine, L-phenylalanine, and L-tryptophan; the second (enzyme B) is active on the aromatic amiono acids. Enzyme A is identical in substrate specificity with transaminase A and is mainly an aspartate aminotransferase; enzyme B has never been described before and is an aromatic amino acid aminotransferase. The two enzymes are different in the Vmax and Km values with their common substrates and pyridoxal phosphate, in heat stability (enzyme A being heat-stable and enzyme B being heat-labile at 55 degrees) and in pH optima with the amino acid substrates. They are similar in their amino acid composition, each enzyme appears to consist of two subunits, and enzyme B may be converted to enzyme A by controlled proteolysis with subtilsin. The conversion was detected by the generation of new aspartate aminotransferase activity from enzyme B and was further verified by identification by acrylamide gel electrophoresis of the newly formed enzyme A. The two enzymes appear to be products of two genes different in a small, probably terminal, nucleotide sequence."}
{"id": "PMID:236312", "title": "Effects of thyroid hormones on enzymes involved in fatty acid and glycerolipid synthesis.", "content": "The influence of thyroid hormones on lipid biosynthesis was studied after administration of L-thyroxine to rats for 5 days. Their weights remained the same as those of control animals, despite an approximately 3-fold increment in plasma L-thyroxine and L-triiodothyronine concentrations. The activity of acetyl-CoA carboxylase and fatty acid synthetase as well as incorporation of tritium into fatty acids were depressed significantly in epididymal adipose tissue and enhanced significantly in livers of thyroxine-treated rats. Using antibodies specific against rat liver fatty acid synthetase, it was determined that the changes in activity of this multienzymic complex were due to alterations in amount of enzyme protein. In the presence of optimal concentrations of fatty acids, radioactive sn-glycero-3-phosphate, and co-substrates, total glycerolipid synthesis (defined in this study as the sum of newly formed radioactive mono- and diacyl-sn-glycero-3-phosphate, diglyceride, and triglyceride) was decreased significantly in adipose tissue and increased in liver and heart. Thus, administration of thyroid hormone results in tissue-specific alterations in lipid biosynthesis which, at least in the case of fatty acid synthetase, are due to changes in enzyme protein content.", "contents": "Effects of thyroid hormones on enzymes involved in fatty acid and glycerolipid synthesis. The influence of thyroid hormones on lipid biosynthesis was studied after administration of L-thyroxine to rats for 5 days. Their weights remained the same as those of control animals, despite an approximately 3-fold increment in plasma L-thyroxine and L-triiodothyronine concentrations. The activity of acetyl-CoA carboxylase and fatty acid synthetase as well as incorporation of tritium into fatty acids were depressed significantly in epididymal adipose tissue and enhanced significantly in livers of thyroxine-treated rats. Using antibodies specific against rat liver fatty acid synthetase, it was determined that the changes in activity of this multienzymic complex were due to alterations in amount of enzyme protein. In the presence of optimal concentrations of fatty acids, radioactive sn-glycero-3-phosphate, and co-substrates, total glycerolipid synthesis (defined in this study as the sum of newly formed radioactive mono- and diacyl-sn-glycero-3-phosphate, diglyceride, and triglyceride) was decreased significantly in adipose tissue and increased in liver and heart. Thus, administration of thyroid hormone results in tissue-specific alterations in lipid biosynthesis which, at least in the case of fatty acid synthetase, are due to changes in enzyme protein content."}
{"id": "PMID:236313", "title": "Heterogeneity of purified mouse interferons.", "content": "A procedure for obtaining highly purified stable interferon from mouse L cells is described. Interferon with a specific activity of 2.5 times 10-8 reference units/mg of protein is composed of 10 to 11 polypeptides. They differ in their molecular size as determined by electrophoresis on polyacrylamide gels containing sodium dodecyl sulfate. The molecular weight range is estimated to be from the smallest at 20, 000 to the largest at 32, 000. At least six of the polypeptides are glycoproteins and each of the polypeptides can be obtained as an apparent homogeneous entity and each has interferon activity.", "contents": "Heterogeneity of purified mouse interferons. A procedure for obtaining highly purified stable interferon from mouse L cells is described. Interferon with a specific activity of 2.5 times 10-8 reference units/mg of protein is composed of 10 to 11 polypeptides. They differ in their molecular size as determined by electrophoresis on polyacrylamide gels containing sodium dodecyl sulfate. The molecular weight range is estimated to be from the smallest at 20, 000 to the largest at 32, 000. At least six of the polypeptides are glycoproteins and each of the polypeptides can be obtained as an apparent homogeneous entity and each has interferon activity."}
{"id": "PMID:236314", "title": "Ribulose diphosphate carboxylase/oxygenase. III. Isolation and properties.", "content": "Similarities in properties of ribulose diphosphate carboxylase and oxygenase activities further substantiate the hypothesis that the same protein catalyzes both reactions. The Km (ribulose diphosphate) is 0.33 mM for the ribulose diphosphate oxygenase, when assayed in air with an oxygen electrode. Maximum activity is obtained with 10 to 35 mM MgCl2. Higher MgCl2 concentrations are inhibitory, but they shift the pH optimum from 9.3 or 9.4 to 8.7 or 9.0. MnCl2 is an effective cofactor of the oxygenase and some activity is obtained with CoCl2. Both the ribulose diphosphate carboxylase and oxygenase activity of the purified protein from spinach leaves are slowly inactivated by storage at 0 degrees and reactivated in 10 min at 50 degrees, provided both 25 mM MgCl2 and 1 mM dithiothreitol are present. The sulfhydryl groups of the enzyme which react rapidly with 5,5'-dithiobis(2-nitrobenzoic acid) are approximately 4 at pH 7.8 and 11 at pH 9.4. At both pH values ribulose diphosphate prevents two of these sulfhydryl groups from reacting with this reagent. About 50% inhibition of the oxygenase activity at pH 9.0 occurs with 50 mM bicarbonate in the presence of 3 mM ribulose diphosphate, and from variations in these parameters the inhibition is attributed to the CO2 species. The purified enzyme of acrylamide gels prevented the reduction of nitroblue tetrazolium in the presence of the superoxide radical, but the enzyme in solution did not react as a superoxide dismutase.", "contents": "Ribulose diphosphate carboxylase/oxygenase. III. Isolation and properties. Similarities in properties of ribulose diphosphate carboxylase and oxygenase activities further substantiate the hypothesis that the same protein catalyzes both reactions. The Km (ribulose diphosphate) is 0.33 mM for the ribulose diphosphate oxygenase, when assayed in air with an oxygen electrode. Maximum activity is obtained with 10 to 35 mM MgCl2. Higher MgCl2 concentrations are inhibitory, but they shift the pH optimum from 9.3 or 9.4 to 8.7 or 9.0. MnCl2 is an effective cofactor of the oxygenase and some activity is obtained with CoCl2. Both the ribulose diphosphate carboxylase and oxygenase activity of the purified protein from spinach leaves are slowly inactivated by storage at 0 degrees and reactivated in 10 min at 50 degrees, provided both 25 mM MgCl2 and 1 mM dithiothreitol are present. The sulfhydryl groups of the enzyme which react rapidly with 5,5'-dithiobis(2-nitrobenzoic acid) are approximately 4 at pH 7.8 and 11 at pH 9.4. At both pH values ribulose diphosphate prevents two of these sulfhydryl groups from reacting with this reagent. About 50% inhibition of the oxygenase activity at pH 9.0 occurs with 50 mM bicarbonate in the presence of 3 mM ribulose diphosphate, and from variations in these parameters the inhibition is attributed to the CO2 species. The purified enzyme of acrylamide gels prevented the reduction of nitroblue tetrazolium in the presence of the superoxide radical, but the enzyme in solution did not react as a superoxide dismutase."}
{"id": "PMID:236315", "title": "The hepatic adenylate cyclase system. II. Substrate binding and utilization and the effects of magnesium ion and pH.", "content": "The kinetic characteristics of substrate utilization by hepatic adenylate cyclase were investigated under a variety of incubation conditions, including veriations in pH, [substrate], [Mg2+], and in the absence or presence of glucagon. Activities were compared with ATP and 5'-adenylylimidodiphosphate (App(NH)p) as substrates. The Km for both substrates was about 50 muM; Vmax given with App(NH)p was about 40% lower than obtained with ATP as substrate. In the presence of a saturating concentration of substrate (1 mM), basal activity was increased 4-fold by increasing [Mg2+] from 5 to 50 mM. The stimulatory effect of Mg2+ was not due to an allosteric action since basal activity was only marginally enhanced (40%) when the substrate concentration was reduced to 10 muM. As suggested by deHaen ((1974 J. Biol. Chem. 249, 2756), it is likely that Mg2+ increases enzyme activity by decreasing the concentration of an inhibitory, unchelated form of substrate that competes with the productive magnesium-substrate complex at the active site. Activity-pH profiles differed with ATP and App(NH)p as substrates; a shift in pH optimum was observed which correlated with the different pKa of the terminal phosphate groups of ATP and App(nh)p, and which reflect the concentration of protonated substrate (ATPH-3 minus) present in the incubation medium. Accordingly, protonated substrate is the predominant inhibitory species of unchelated substrate and probably has a considerably higher affinity for the active site than does the magnesium-substrate complex. Glucagon-stimulated activity was less susceptible to inhibition by protonated substrate than is the basal state as evidenced by lower stimulatory effect when the [Mg2+] was increased from 5 to 20 mM. However, increasing the [Mg2+] from 20 to 50 mM resulted in marked inhibition of glucagon-stimulated activity, particularly in the presence of 10 muM substrate. Conversely, at a fixed [Mg2+], concentrations of substrate at least 20-fold higher than the Km were required to achieve maximal hormone-stimulated activity. These findings suggest that the unchelated, fully ionized form of substrate serves as an activating ligand, as has been observed with guanine nucleotides at considerably lower concentrations. Thus, Mg2+ affects adenylate cyclase activity by forming the productive substrate complex and by titrating the inhibitory protonated and activating free forms of substrate. As a result of these effects of unchelated substrate, it proved difficult to evaluate the kinetic parameters involved in substrate binding and utilization and the effects of hormone thereon when substrate was added as the only source of activating ligand. However, linear Michaelis kinetic data were obtained by adding the activating ligand 5'-guanylylimidodiphosphate with glucagon and by making appropriate adjustments of pH and [Mg2+]. Vmax was increased 4-fold without changes in Km by the actions of 5'-guanylylimidodiphosphate and glucagon.", "contents": "The hepatic adenylate cyclase system. II. Substrate binding and utilization and the effects of magnesium ion and pH. The kinetic characteristics of substrate utilization by hepatic adenylate cyclase were investigated under a variety of incubation conditions, including veriations in pH, [substrate], [Mg2+], and in the absence or presence of glucagon. Activities were compared with ATP and 5'-adenylylimidodiphosphate (App(NH)p) as substrates. The Km for both substrates was about 50 muM; Vmax given with App(NH)p was about 40% lower than obtained with ATP as substrate. In the presence of a saturating concentration of substrate (1 mM), basal activity was increased 4-fold by increasing [Mg2+] from 5 to 50 mM. The stimulatory effect of Mg2+ was not due to an allosteric action since basal activity was only marginally enhanced (40%) when the substrate concentration was reduced to 10 muM. As suggested by deHaen ((1974 J. Biol. Chem. 249, 2756), it is likely that Mg2+ increases enzyme activity by decreasing the concentration of an inhibitory, unchelated form of substrate that competes with the productive magnesium-substrate complex at the active site. Activity-pH profiles differed with ATP and App(NH)p as substrates; a shift in pH optimum was observed which correlated with the different pKa of the terminal phosphate groups of ATP and App(nh)p, and which reflect the concentration of protonated substrate (ATPH-3 minus) present in the incubation medium. Accordingly, protonated substrate is the predominant inhibitory species of unchelated substrate and probably has a considerably higher affinity for the active site than does the magnesium-substrate complex. Glucagon-stimulated activity was less susceptible to inhibition by protonated substrate than is the basal state as evidenced by lower stimulatory effect when the [Mg2+] was increased from 5 to 20 mM. However, increasing the [Mg2+] from 20 to 50 mM resulted in marked inhibition of glucagon-stimulated activity, particularly in the presence of 10 muM substrate. Conversely, at a fixed [Mg2+], concentrations of substrate at least 20-fold higher than the Km were required to achieve maximal hormone-stimulated activity. These findings suggest that the unchelated, fully ionized form of substrate serves as an activating ligand, as has been observed with guanine nucleotides at considerably lower concentrations. Thus, Mg2+ affects adenylate cyclase activity by forming the productive substrate complex and by titrating the inhibitory protonated and activating free forms of substrate. As a result of these effects of unchelated substrate, it proved difficult to evaluate the kinetic parameters involved in substrate binding and utilization and the effects of hormone thereon when substrate was added as the only source of activating ligand. However, linear Michaelis kinetic data were obtained by adding the activating ligand 5'-guanylylimidodiphosphate with glucagon and by making appropriate adjustments of pH and [Mg2+]. Vmax was increased 4-fold without changes in Km by the actions of 5'-guanylylimidodiphosphate and glucagon."}
{"id": "PMID:236316", "title": "[127-I]- or carrier-free [125-I]monoiodoinsulin.", "content": "Insulin was enzymatically moniodinated with 127-I or 125-I, and an improved method of purification by anion exchange chromatography was employed. (127-I)Monoiodoinsulin was identified by spectrophotometric analysis and its molar extinction coefficient determined to be 6.31 times 10-3 M-1 cm minus 1. The observed specific activity of carrier-free (125-I)monoidoinsulin was close to the theoretical value (378mCi/mg). The monoiodotyrosyl residue of monoidoinsulin was shown to be solvent-exposed. The ionic properties of the substituted hormone were altered at pH values close to the pK of monoiodotyrosine (8.85), but the pI was unchanged (5.65). (127-I)Monoiodoinsulin formed rhombohedral crystals and co-crystallized with native insulin. Monoidoinsulin was indistinguishable from insulin with respect to binding to two out of three guinea pig anti-insulin sera, to binding to IM9 cultured human lymphocytes, and to binding to isolated rat hepatocyte plasma membranes. The potency of monoidoinsulin was not statistically different from that of insulin in the rat fat cell bioassay and in the mouse convulsion assay. An insulin-degrading enzyme extracted from rat liver degraded monoiodoinsulin less readily than native insulin; monoiodoinsulin was a competitive inhibitor of insulin degradation, and the Km values were 30 nM AND 78 NM for monoidoinsulin and native insulin, respectively. It is concluded that monoidination does not markedly alter the three-dimensional structure of the molecule and that only a few sensitive biological systems are able to distinguish the monoidinated from the native hormone.", "contents": "[127-I]- or carrier-free [125-I]monoiodoinsulin. Insulin was enzymatically moniodinated with 127-I or 125-I, and an improved method of purification by anion exchange chromatography was employed. (127-I)Monoiodoinsulin was identified by spectrophotometric analysis and its molar extinction coefficient determined to be 6.31 times 10-3 M-1 cm minus 1. The observed specific activity of carrier-free (125-I)monoidoinsulin was close to the theoretical value (378mCi/mg). The monoiodotyrosyl residue of monoidoinsulin was shown to be solvent-exposed. The ionic properties of the substituted hormone were altered at pH values close to the pK of monoiodotyrosine (8.85), but the pI was unchanged (5.65). (127-I)Monoiodoinsulin formed rhombohedral crystals and co-crystallized with native insulin. Monoidoinsulin was indistinguishable from insulin with respect to binding to two out of three guinea pig anti-insulin sera, to binding to IM9 cultured human lymphocytes, and to binding to isolated rat hepatocyte plasma membranes. The potency of monoidoinsulin was not statistically different from that of insulin in the rat fat cell bioassay and in the mouse convulsion assay. An insulin-degrading enzyme extracted from rat liver degraded monoiodoinsulin less readily than native insulin; monoiodoinsulin was a competitive inhibitor of insulin degradation, and the Km values were 30 nM AND 78 NM for monoidoinsulin and native insulin, respectively. It is concluded that monoidination does not markedly alter the three-dimensional structure of the molecule and that only a few sensitive biological systems are able to distinguish the monoidinated from the native hormone."}
{"id": "PMID:236317", "title": "Reaction of N-acetylglucosamine oligosaccharides with lysozyme. Temperature, pH, and solvent deuterium isotope effects; equilbrium, steady state, and pre-steady state measurements*.", "content": "Temperature jump and stopped flow methods were used to study at pH 7.0 the temperature dependence of elementary steps of the reactions of lysozyme with the beta(1 yields 4)-linked trimer, tetramer, and hexamer of N-acetylglucosamine. The steady state rate of cleavage of the hexasaccharide was determined as a function of temperature (5 degrees-40 degrees) and pH(2 to 8) in H-2O solution and as a function of pD(2.5 to 9.5) at 40 degrees in D-2O solution. The apparent enthalpies of the two ionizations of apparent pK 3.8 and 6.7 observed in measurements of k are 0 to 2 kcal/mol. The energy of activation determined for the pH optimum is 21.5 kcal/mol. The solvent deuterium isotope effect measured for k at the pH (pD) optimum is 1.5 And reflects isotope effects on pre-equilibrium steps and on the rate-determining step. Transfer from H-2O to D-2O solution produces 0.2 to 0.4 kcal/mol more negative free energies of saccharide binding and no changes in the enthalpies of binding. Pre-steady state, steady state, and equilibrium measurements indicate a pathway for the reaction of lysozyme with hexasaccharide. The results define for this mechanism the complete free energy profile and an essentially complete enthalpy profile. Three of the five observable ES complexes are present at nearly equal concentrations. The free energies of the transition states are within a range of 3 kcal. The enthalpies of productive enzyme-substrate complexes are about 5 kcal/mol greater than the enthalpies of nonproductive complexes. Changes in tryptophan fluorescence were observed for each elementary step, and changes in pK of Glu-35 for the isomerizations of nonproductive and productive complexes. The signal changes during formation of nonproductive complexes are the same for the oligosaccharides (ClcNAc)3 to (GlcNAc)6. The changes for productive complexes are similar but not identical with saccharides (GlcNAc)4 to (GlcNAc)6. Correlations of the present data with previous crystallographic and solution measurements indicate the structures of productive and nonproductive ES complexes and suggest that full interaction of the substrate with the enzyme active site is established in the rate-determining step.", "contents": "Reaction of N-acetylglucosamine oligosaccharides with lysozyme. Temperature, pH, and solvent deuterium isotope effects; equilbrium, steady state, and pre-steady state measurements*. Temperature jump and stopped flow methods were used to study at pH 7.0 the temperature dependence of elementary steps of the reactions of lysozyme with the beta(1 yields 4)-linked trimer, tetramer, and hexamer of N-acetylglucosamine. The steady state rate of cleavage of the hexasaccharide was determined as a function of temperature (5 degrees-40 degrees) and pH(2 to 8) in H-2O solution and as a function of pD(2.5 to 9.5) at 40 degrees in D-2O solution. The apparent enthalpies of the two ionizations of apparent pK 3.8 and 6.7 observed in measurements of k are 0 to 2 kcal/mol. The energy of activation determined for the pH optimum is 21.5 kcal/mol. The solvent deuterium isotope effect measured for k at the pH (pD) optimum is 1.5 And reflects isotope effects on pre-equilibrium steps and on the rate-determining step. Transfer from H-2O to D-2O solution produces 0.2 to 0.4 kcal/mol more negative free energies of saccharide binding and no changes in the enthalpies of binding. Pre-steady state, steady state, and equilibrium measurements indicate a pathway for the reaction of lysozyme with hexasaccharide. The results define for this mechanism the complete free energy profile and an essentially complete enthalpy profile. Three of the five observable ES complexes are present at nearly equal concentrations. The free energies of the transition states are within a range of 3 kcal. The enthalpies of productive enzyme-substrate complexes are about 5 kcal/mol greater than the enthalpies of nonproductive complexes. Changes in tryptophan fluorescence were observed for each elementary step, and changes in pK of Glu-35 for the isomerizations of nonproductive and productive complexes. The signal changes during formation of nonproductive complexes are the same for the oligosaccharides (ClcNAc)3 to (GlcNAc)6. The changes for productive complexes are similar but not identical with saccharides (GlcNAc)4 to (GlcNAc)6. Correlations of the present data with previous crystallographic and solution measurements indicate the structures of productive and nonproductive ES complexes and suggest that full interaction of the substrate with the enzyme active site is established in the rate-determining step."}
{"id": "PMID:236318", "title": "Adenosine triphosphate-induced motility and sliding of filaments in mammalian sperm extracted with Triton X-100.", "content": "Bull sperm that had been extracted with 0.2% Triton X-100 could be reactivated with ATP, and their movement closely resembled the motion of intact live sperm. Their motility required the presence of ATP, magnesium, and a medium of suitable salt concentration and pH. When Triton-extracted bull sperm were digested breifly with trypsin at pH 9.0, they appeared to reatin most of their normal structure, but subsequent exposure of the digested sperm to ATP caused a disintegration by light microscopy, using dark-field illumination, combined with an electron microscope study of preparations of the disintegrated sperm, demonstrated the presence of an active sliding mechanism of filament interaction in bull spermatozoa. Human sperm subjected to the same procedures showed similar patterns of reactivation and of disintegration.", "contents": "Adenosine triphosphate-induced motility and sliding of filaments in mammalian sperm extracted with Triton X-100. Bull sperm that had been extracted with 0.2% Triton X-100 could be reactivated with ATP, and their movement closely resembled the motion of intact live sperm. Their motility required the presence of ATP, magnesium, and a medium of suitable salt concentration and pH. When Triton-extracted bull sperm were digested breifly with trypsin at pH 9.0, they appeared to reatin most of their normal structure, but subsequent exposure of the digested sperm to ATP caused a disintegration by light microscopy, using dark-field illumination, combined with an electron microscope study of preparations of the disintegrated sperm, demonstrated the presence of an active sliding mechanism of filament interaction in bull spermatozoa. Human sperm subjected to the same procedures showed similar patterns of reactivation and of disintegration."}
{"id": "PMID:236319", "title": "Acetylcholine receptor turnover in membranes of developing muscle fibers.", "content": "[125I mono-iodo-alpha-bungarotoxin is used as a specific marker in a description of acetylcholine receptor metabolism. It is concluded that acetylcholine receptors in the surface membranes of chick and rat myotubes developing in cell cultures have a  half-life of 22-24 h. Alpha-bungarotoxin (bound to a receptor which is removed from the membrane) is degraded to monoiodotyrosine which appears in the medium. Several observations are consistent with a model in which receptors or alpha-bungarotoxin-receptor complexes are internalized and then degraded: (a) the rate of appearance of iodotyrosine does not reach its maximal rate until 90 min after alpha-bungarotoxin is bound to the surface receptors; (b) 2,4-dinitrophenol, reduced temperature, and cell disruption all inhibit the degradation process. The degradation of surface receptors is not coupled to the process by which receptors are incorporated into the membrane. Evidence suggest that receptors are incorporated into the surface membrane from a presynthesized set of receptors containing about 10% as many alpha-bungarotoxin binding sites as does the surface. Additionally, a third set of acetylcholine receptors is described containing about 30% as amny binding sites as does the surface. These \"hidden\" recptors are not precursors yet are not readily accessible for binding of extracellular alpha-bungarotoxin. These findings are discussed in relation to both plasma membrane biosynthesis and control of chemosensitivity in developing and denervated skeletal muscle.", "contents": "Acetylcholine receptor turnover in membranes of developing muscle fibers. [125I mono-iodo-alpha-bungarotoxin is used as a specific marker in a description of acetylcholine receptor metabolism. It is concluded that acetylcholine receptors in the surface membranes of chick and rat myotubes developing in cell cultures have a  half-life of 22-24 h. Alpha-bungarotoxin (bound to a receptor which is removed from the membrane) is degraded to monoiodotyrosine which appears in the medium. Several observations are consistent with a model in which receptors or alpha-bungarotoxin-receptor complexes are internalized and then degraded: (a) the rate of appearance of iodotyrosine does not reach its maximal rate until 90 min after alpha-bungarotoxin is bound to the surface receptors; (b) 2,4-dinitrophenol, reduced temperature, and cell disruption all inhibit the degradation process. The degradation of surface receptors is not coupled to the process by which receptors are incorporated into the membrane. Evidence suggest that receptors are incorporated into the surface membrane from a presynthesized set of receptors containing about 10% as many alpha-bungarotoxin binding sites as does the surface. Additionally, a third set of acetylcholine receptors is described containing about 30% as amny binding sites as does the surface. These \"hidden\" recptors are not precursors yet are not readily accessible for binding of extracellular alpha-bungarotoxin. These findings are discussed in relation to both plasma membrane biosynthesis and control of chemosensitivity in developing and denervated skeletal muscle."}
{"id": "PMID:236320", "title": "Studies of the human testis. V. Properties of delta-5-3beta and 17beta-hydroxysteroid dehydrogenases in the biosynthesis of testosterone from dehydroepiandrosterone.", "content": "The properties of delta-5-3beta-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid dehydrogenase in the human testis were examined using cell-free homogenates with added cofactors. Michaelis constants of the delta-5-3beta-hydroxysteroid dehydrogenase enzyme at 37 C and pH 7.4 were 8.2 times 10 minus 7M for dehydroepiandrosterone and 2.9 times 10 minus 6M for androstenediol. The optimal pH for both substrates was approximately 8.15. Dehydroepiandrosterone and androstenediol are competitive substrates for the enzyme. When free and conjugated C19 steroids in the order of 10 minus 6 were added, androstenedione and testosterone inhibited the enzyme activity for dehydroepiandrosterone while the activity for androstenediol was inhibited by addition of dehydroepiandrosterone and its sulfate as well as by androstenedione and testosterone. 17beta-Hydroxysteroid dehydrogenase had two apparent Michaelis constants for dehydroepiandrosterone, 3.3 times 10 minus 6M at low substrate concentrations and 1 times 10 minus 5M at high substrate concentrations. The enzyme activities for dehydroepiandrosterone and androstenedione were found to be enhanced by addition of the 17beta-hydroxysteroids examined and slightly inhibited by addition of dehydroepiandrosterone-sulfate and androstenediol-3-monosulfate. Androstenedione caused an inhibition of the 17beta-hydroxysteroid dehydrogenase for dehydroepiandrosterone. The interconversion between androstenedione and testosterone by the enzyme favored testosterone formation. Following simultaneous incubation of 3H-dehydroepiandrosterone and 14C-androstenediol in equal amounts, initially more testosterone was produced from dehydroepiandrosterone than from androstenediol under the conditions employed, while subsequently with accumulation of androstenediol more testosterone was produced from androstenediol.", "contents": "Studies of the human testis. V. Properties of delta-5-3beta and 17beta-hydroxysteroid dehydrogenases in the biosynthesis of testosterone from dehydroepiandrosterone. The properties of delta-5-3beta-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid dehydrogenase in the human testis were examined using cell-free homogenates with added cofactors. Michaelis constants of the delta-5-3beta-hydroxysteroid dehydrogenase enzyme at 37 C and pH 7.4 were 8.2 times 10 minus 7M for dehydroepiandrosterone and 2.9 times 10 minus 6M for androstenediol. The optimal pH for both substrates was approximately 8.15. Dehydroepiandrosterone and androstenediol are competitive substrates for the enzyme. When free and conjugated C19 steroids in the order of 10 minus 6 were added, androstenedione and testosterone inhibited the enzyme activity for dehydroepiandrosterone while the activity for androstenediol was inhibited by addition of dehydroepiandrosterone and its sulfate as well as by androstenedione and testosterone. 17beta-Hydroxysteroid dehydrogenase had two apparent Michaelis constants for dehydroepiandrosterone, 3.3 times 10 minus 6M at low substrate concentrations and 1 times 10 minus 5M at high substrate concentrations. The enzyme activities for dehydroepiandrosterone and androstenedione were found to be enhanced by addition of the 17beta-hydroxysteroids examined and slightly inhibited by addition of dehydroepiandrosterone-sulfate and androstenediol-3-monosulfate. Androstenedione caused an inhibition of the 17beta-hydroxysteroid dehydrogenase for dehydroepiandrosterone. The interconversion between androstenedione and testosterone by the enzyme favored testosterone formation. Following simultaneous incubation of 3H-dehydroepiandrosterone and 14C-androstenediol in equal amounts, initially more testosterone was produced from dehydroepiandrosterone than from androstenediol under the conditions employed, while subsequently with accumulation of androstenediol more testosterone was produced from androstenediol."}
{"id": "PMID:236321", "title": "Total body retention of orally administered 47-calcium in primary hyperparathyroidism.", "content": "Using a whole body radiation detector, we have measured the total body retention of 47-Ca 7 days after oral administration of the isotope to patients with various disorders of calcium metabolism. The percent retention of 47-Ca given with 90 mg of unlabeled (carrier) calcium varied with the calcium metabolic status as follows: normals (n equals 14), 33-43 percent (mean 38); primary hyperparathyroidism (n equals 28), 32-74 percent (mean 52); idiopathic hypercalciuria (n equals 9), 34-49 percent (mean 42); and hypercalcemia of other etiology (n equals 3), 23-26 percent (mean 25). Almost half (13/28) of those with hyperparathyroidism showed a retention above 55 percent, distinguishing them from subjects with idiopathic hypercalciuria. Retention of 47-Ca correlated poorly with clinical measures of severity of hyperparathyroidism. When isotope was diluted with a smaller amount of carrier calcium (20 mg), retention was increaseed in normals (n equals 5) to 46-54 percent (mean 50) and in hyperparathyroidism (n equals 5) to 64-87 percent (mean 73). After surgical cure of  hyperparathyroidism retention of isotope returned  toward normal in 5 of 7 subjects. Whole body retention of orally administered 47-Ca may prove useful in detecting hyperparathyroidism in subjects with mild hypercalcemia or hypercalciuria.", "contents": "Total body retention of orally administered 47-calcium in primary hyperparathyroidism. Using a whole body radiation detector, we have measured the total body retention of 47-Ca 7 days after oral administration of the isotope to patients with various disorders of calcium metabolism. The percent retention of 47-Ca given with 90 mg of unlabeled (carrier) calcium varied with the calcium metabolic status as follows: normals (n equals 14), 33-43 percent (mean 38); primary hyperparathyroidism (n equals 28), 32-74 percent (mean 52); idiopathic hypercalciuria (n equals 9), 34-49 percent (mean 42); and hypercalcemia of other etiology (n equals 3), 23-26 percent (mean 25). Almost half (13/28) of those with hyperparathyroidism showed a retention above 55 percent, distinguishing them from subjects with idiopathic hypercalciuria. Retention of 47-Ca correlated poorly with clinical measures of severity of hyperparathyroidism. When isotope was diluted with a smaller amount of carrier calcium (20 mg), retention was increaseed in normals (n equals 5) to 46-54 percent (mean 50) and in hyperparathyroidism (n equals 5) to 64-87 percent (mean 73). After surgical cure of  hyperparathyroidism retention of isotope returned  toward normal in 5 of 7 subjects. Whole body retention of orally administered 47-Ca may prove useful in detecting hyperparathyroidism in subjects with mild hypercalcemia or hypercalciuria."}
{"id": "PMID:236322", "title": "Accelerated host metabolism of L-thyroxine during acute infection: role of the leukocyte and peripheral leukocytosis.", "content": "Metabolism of thyroid hormones is accelerated during acute infection in man and in experimental animals. The pathogenetic mechanisms mediating this phenomenon are uncertain, but activated leukocytes of the infected host have been implicated as potentially important sites of hormone degradation. The present studies were conducted in an attempt to assess the in vivo contribution of leukocytes and peripheral leukocytosis to the enhancement of L-thyroxine (T4) clearance seen during infection, and to evaluate further the possible roles of fever and of changes in the extracellular binding of T4. In 10 rhesus monkeys inoculated with virulent yellow fever (YF) virus, peripheral disposal of T4 was significantly accelerated (2-fold) during the febrile phase of the illness. This experimental viral infection was not accompanied by neutrophilic leukocytosis nor by detectable changes in serum free T4 levels, suggesting that neither an increased circulating neutrophil mass nor diminished extracellular binding of T4 contributed appreciably to the increase in metabolism of T4. A pathogenetic role for fever in the enhancement of T4 degradation was not specifically excluded in these infected monkeys. However, the failure of T4 turnover to increase during other febrile infections, such as that which followed inoculation of monkeys with Venezuelan equine encephalitis virus, indicates that the acceleration of peripheral disposal of T4 seen in infection is not a simple concomitant of fever. In monkeys with bacterial sepsis and in those inoculated iv with zymosan particles, T4 turnover was similarly accelerated in the absence of detectable changes in serum free T4 levels, suggesting a pathogenetic role for enhances cellular uptake and metabolism of hormone. However, in these monkeys deiodination of T4 by leukocytes did not appear to account for the increase in T4 disposal. During sepsis and following zymosan administration, T4 turnover was markedly increased in both intact monkeys with a neutrophilic leukocytosis and in those with irradiation-induced neutropenia. Therefore, the cellular sites of increased T4 degradation during infection remain uncertain. Fixed tissue macrophages serve as the major site of clearance of YF virus, circulating bacteria and zymosan particles. Accordingly, a relationship between activation of these phagocytic cells and the acceleration of T4 metabolism seemed possible but was not established by our studies.", "contents": "Accelerated host metabolism of L-thyroxine during acute infection: role of the leukocyte and peripheral leukocytosis. Metabolism of thyroid hormones is accelerated during acute infection in man and in experimental animals. The pathogenetic mechanisms mediating this phenomenon are uncertain, but activated leukocytes of the infected host have been implicated as potentially important sites of hormone degradation. The present studies were conducted in an attempt to assess the in vivo contribution of leukocytes and peripheral leukocytosis to the enhancement of L-thyroxine (T4) clearance seen during infection, and to evaluate further the possible roles of fever and of changes in the extracellular binding of T4. In 10 rhesus monkeys inoculated with virulent yellow fever (YF) virus, peripheral disposal of T4 was significantly accelerated (2-fold) during the febrile phase of the illness. This experimental viral infection was not accompanied by neutrophilic leukocytosis nor by detectable changes in serum free T4 levels, suggesting that neither an increased circulating neutrophil mass nor diminished extracellular binding of T4 contributed appreciably to the increase in metabolism of T4. A pathogenetic role for fever in the enhancement of T4 degradation was not specifically excluded in these infected monkeys. However, the failure of T4 turnover to increase during other febrile infections, such as that which followed inoculation of monkeys with Venezuelan equine encephalitis virus, indicates that the acceleration of peripheral disposal of T4 seen in infection is not a simple concomitant of fever. In monkeys with bacterial sepsis and in those inoculated iv with zymosan particles, T4 turnover was similarly accelerated in the absence of detectable changes in serum free T4 levels, suggesting a pathogenetic role for enhances cellular uptake and metabolism of hormone. However, in these monkeys deiodination of T4 by leukocytes did not appear to account for the increase in T4 disposal. During sepsis and following zymosan administration, T4 turnover was markedly increased in both intact monkeys with a neutrophilic leukocytosis and in those with irradiation-induced neutropenia. Therefore, the cellular sites of increased T4 degradation during infection remain uncertain. Fixed tissue macrophages serve as the major site of clearance of YF virus, circulating bacteria and zymosan particles. Accordingly, a relationship between activation of these phagocytic cells and the acceleration of T4 metabolism seemed possible but was not established by our studies."}
{"id": "PMID:236323", "title": "Plasma testosterone in patients with varicocele and sexual inadequacy.", "content": "Plasma testosterone concentration was decreased in 10 patients combining varicocele with sexual inadequacy (mean 346.2 ng/100 ml) against normal concentration observed in 23 men with varicocele without sexual disturbances (mean 567.8 ng/100 ml) and in 31 patients with pure psychogenic impotence (mean 581.6 ng/100 ml). There was a significant inverse linear correlation between age and plasma testosterone concentration in the varicocele patients (r= minus 0.56, P smaller than 0.01) in contrast to the absence of such correlation in normal men or in patients with psychogenic impotence of the same age range. The secretion products of the secondary sex glands were more often in the lower range in the ejaculates of men combining varicocele with sexual disturbance (P smaller than 0.02), proving the decreased testosterone level to induce a deficient function of these glands. Plasma testosterone levels normalized after surgical correction in varicocele patients with a low preoperative concentration. Since adequate surgical or hormonal treatment resulted in complete recovery of sexual potency in the majority of patients with varicocele and sexual inadequacy, it is suggested that the decreased testosterone production might have contributed to the impairment of sexual function.", "contents": "Plasma testosterone in patients with varicocele and sexual inadequacy. Plasma testosterone concentration was decreased in 10 patients combining varicocele with sexual inadequacy (mean 346.2 ng/100 ml) against normal concentration observed in 23 men with varicocele without sexual disturbances (mean 567.8 ng/100 ml) and in 31 patients with pure psychogenic impotence (mean 581.6 ng/100 ml). There was a significant inverse linear correlation between age and plasma testosterone concentration in the varicocele patients (r= minus 0.56, P smaller than 0.01) in contrast to the absence of such correlation in normal men or in patients with psychogenic impotence of the same age range. The secretion products of the secondary sex glands were more often in the lower range in the ejaculates of men combining varicocele with sexual disturbance (P smaller than 0.02), proving the decreased testosterone level to induce a deficient function of these glands. Plasma testosterone levels normalized after surgical correction in varicocele patients with a low preoperative concentration. Since adequate surgical or hormonal treatment resulted in complete recovery of sexual potency in the majority of patients with varicocele and sexual inadequacy, it is suggested that the decreased testosterone production might have contributed to the impairment of sexual function."}
{"id": "PMID:236324", "title": "Effects of morphine on coronary and left ventricular dynamics in conscious dogs.", "content": "We studied the effects of i.v. 2 mg/kg morphine sulfate (MS) on coronary blood flow and resistance, left ventricular (LV) diameter and pressure (P), rate of change of pressure (dP/dt), and dP/dt/P in conscious dogs. An initial transient reduction in coronary vascular resistance, associated with increases in heart rate, dP/dt, dP/dt/P, and reductions in LV end-diastolic and end-systolic size were observed. This was followed by a prolonged increase in mean coronary vascular resistance, lasting from 5 to 30 min, while heart rate, arterial pressure, and LV end-diastolic diameter returned to control levels and dP/dt/P remained slightly but significantly above control. At 10 min, late diastolic coronary flow had fallen from 44 plus or minus 3 ml/min to a minimum level of 25 plus or minus 3 ml/min, while late diastolic coronary resistance had risen from 1.68 plus or minus 0.10 to 3.04 plus or minus 0.28 mm Hg/ml/min. Morphine also induced substantial coronary vasoconstriction when heart rate was held constant. Neither the MS-induced coronary vasoconstriction nor the positive inotropic response was abolished by bilateral adrenalectomy. The positive inotropic response of MS was reversed after beta blockade, but not the coronary vasoconstriction. Alpha receptor blockade abolished the late coronary vasoconstriction effects of morphine, and only dilatation occurred. In anesthetized dogs MS failed to produce late coronary vasoconstriction. Coronary after a respiratory-depressant dose of morphine, 10 mg/kg i.v. Smaller doses of MS, 0.25 mg/kg every 15 min, produced significant coronary vasoconstriction after a total dose of 0.75 mg/kg in the conscious dogs. The effects of morphine may differ in the normal dog and man and may vary depending upon the presence or absence of coronary artery disease. However, in the normal conscious dog, MS elicits a mild beta adrenergic increase in contractility and an important coronary vasoconstrictor effect, which is mediated through alpha adrenergic receptors.", "contents": "Effects of morphine on coronary and left ventricular dynamics in conscious dogs. We studied the effects of i.v. 2 mg/kg morphine sulfate (MS) on coronary blood flow and resistance, left ventricular (LV) diameter and pressure (P), rate of change of pressure (dP/dt), and dP/dt/P in conscious dogs. An initial transient reduction in coronary vascular resistance, associated with increases in heart rate, dP/dt, dP/dt/P, and reductions in LV end-diastolic and end-systolic size were observed. This was followed by a prolonged increase in mean coronary vascular resistance, lasting from 5 to 30 min, while heart rate, arterial pressure, and LV end-diastolic diameter returned to control levels and dP/dt/P remained slightly but significantly above control. At 10 min, late diastolic coronary flow had fallen from 44 plus or minus 3 ml/min to a minimum level of 25 plus or minus 3 ml/min, while late diastolic coronary resistance had risen from 1.68 plus or minus 0.10 to 3.04 plus or minus 0.28 mm Hg/ml/min. Morphine also induced substantial coronary vasoconstriction when heart rate was held constant. Neither the MS-induced coronary vasoconstriction nor the positive inotropic response was abolished by bilateral adrenalectomy. The positive inotropic response of MS was reversed after beta blockade, but not the coronary vasoconstriction. Alpha receptor blockade abolished the late coronary vasoconstriction effects of morphine, and only dilatation occurred. In anesthetized dogs MS failed to produce late coronary vasoconstriction. Coronary after a respiratory-depressant dose of morphine, 10 mg/kg i.v. Smaller doses of MS, 0.25 mg/kg every 15 min, produced significant coronary vasoconstriction after a total dose of 0.75 mg/kg in the conscious dogs. The effects of morphine may differ in the normal dog and man and may vary depending upon the presence or absence of coronary artery disease. However, in the normal conscious dog, MS elicits a mild beta adrenergic increase in contractility and an important coronary vasoconstrictor effect, which is mediated through alpha adrenergic receptors."}
{"id": "PMID:236325", "title": "Altered renin release and propranolol potentiation of vasodilatory drug hypotension.", "content": "Vasodilating antihypertensive drugs induce hypotension with reflex tachycardia, renin release, and fluid and electrolyte retention. Propranolol can impair this renin release. The studies described here were designed to determine the hemodynamic role of vasodilatory drug-induced renin release and inhibition thereof by propranolol in two animals models, the unanesthetized, normotensive and the unanesthetized, genetically hypertensive rat. In studies with normotensive rats, propranolol impaired renin release and tachycardia resulting from hydralazine and minoxidil and potentiated their hypotensive action. Two additional interventions against the renin-angiotensin system were used in evaluating the mechanism of this potentiation. One was removal of the renin source by nephrectomy, and the second was blockade of angiotensin's vasoconstrictor action using a selective angiotensin antagonist, saralasin (1-Sar-8-Ala-angiotensin II (previously known as P113)).. Both interventions potentiated vasocilatory drug hypotension, as did propranolol, but did not prevent reflex tachycardia. When combined with saralasin propranolol did not add to protentiation by this peptide. A similar pattern of blood pressure decrement and potentiation was seen in genetically hypertensive rats when propranolol or saralasin treatment preceded hydralazine. Propranolol was demonstrated to block hydralazine-induced increases in serum renin activity in genetically hypertensive rats. We conclude that hypotensive potentiation of vasocilating drugs by propranolol in these animal models is mediated to a large extent by impairment of renin release. Persistence of hypotensive tachycardia after nephrectomy and after saralasin in normotensive rats suggests the irrelevance of angiotensin's central nervous system stimulation to this cardiac effect. Clinical studies are underway to quantify the potential importance of this beneficial drug interaction in man.", "contents": "Altered renin release and propranolol potentiation of vasodilatory drug hypotension. Vasodilating antihypertensive drugs induce hypotension with reflex tachycardia, renin release, and fluid and electrolyte retention. Propranolol can impair this renin release. The studies described here were designed to determine the hemodynamic role of vasodilatory drug-induced renin release and inhibition thereof by propranolol in two animals models, the unanesthetized, normotensive and the unanesthetized, genetically hypertensive rat. In studies with normotensive rats, propranolol impaired renin release and tachycardia resulting from hydralazine and minoxidil and potentiated their hypotensive action. Two additional interventions against the renin-angiotensin system were used in evaluating the mechanism of this potentiation. One was removal of the renin source by nephrectomy, and the second was blockade of angiotensin's vasoconstrictor action using a selective angiotensin antagonist, saralasin (1-Sar-8-Ala-angiotensin II (previously known as P113)).. Both interventions potentiated vasocilatory drug hypotension, as did propranolol, but did not prevent reflex tachycardia. When combined with saralasin propranolol did not add to protentiation by this peptide. A similar pattern of blood pressure decrement and potentiation was seen in genetically hypertensive rats when propranolol or saralasin treatment preceded hydralazine. Propranolol was demonstrated to block hydralazine-induced increases in serum renin activity in genetically hypertensive rats. We conclude that hypotensive potentiation of vasocilating drugs by propranolol in these animal models is mediated to a large extent by impairment of renin release. Persistence of hypotensive tachycardia after nephrectomy and after saralasin in normotensive rats suggests the irrelevance of angiotensin's central nervous system stimulation to this cardiac effect. Clinical studies are underway to quantify the potential importance of this beneficial drug interaction in man."}
{"id": "PMID:236326", "title": "The ionic control of 1,25-dihydroxyvitamin D3 production in isolated chick renal tubules.", "content": "Isolated renal tubules prepared from vitamin D-deficient chicks catalyze the 1 alpha-hydroxylation of 25-hydroxyvitamin D3 (250HD3) in vitro. The effect of calcium and phosphate on the rate of synthesis of the product, 1, 25-dihydroxyvitamin D3 (1,25(OH)2D3), was studied at two levels: the long-term effects of various dietary calcium and phosphate contents on the ability of the tubules to produce 1, 25 (OH)2D3, and the acute effects of different calcium and phosphate concentrations in the incubation medium on the rate of synthesis of 1,25(OH)2D3 by the tubules. Manipulation of dietary calcium and phosphate sufficient to produce marked changes in the concentration of calcium and phosphate in the serum led to altered rates of 1,25(OH)2D3 synthesis by the isolated renal tubules. The renal tubules isolated from chicks raised on a vitamin D-deficient diet containing 0.43% calcium and 0.3% P as inorganic phosphate showed the highest rate of synthesis of 1,25(OH)2D3. Diets containing more or less of either calcium or phosphate produced chicks whose renal tubules had a slower rate of 1,25(OH)2D3 production. The calcium, phosphate, and hydrogen ion content of the incubation medium were manipulated to determine the possible factors concerned with the immediate regulation of 1,25(OH)2D3 production. A calcium concentration of 0.5-1.0 mM was necessary for optimal enzymatic activity. Concentrations of calcium greater than this optimal concentration inhibited 1,25(OH)2D3 production if phosphate was also present, and this inhibition was more pronounced as the phosphate concentration was increased. The stimulation of 1,25(OH)2D3 production by calcium was less at pH 6.7 than at 7.4. Raising the phosphate concentration from 0 to 6 mM in the absence of calcium also stimulated the rate of synthesis of 1,25(OH)2D3. This stimulatory effect was blocked by 4 mM calcium. However, at 1-2 mM calciu, phosphate had a biphasic influence on 1,25(OH)2D3 production; extracellular concentrations of phosphate from 0.6 to 1.2 mM resulted in less 1,25(OH)2D3 production than higher or lower phosphate concentrations. This biphasic effect was seen both at pH 7.4 and 6.8.", "contents": "The ionic control of 1,25-dihydroxyvitamin D3 production in isolated chick renal tubules. Isolated renal tubules prepared from vitamin D-deficient chicks catalyze the 1 alpha-hydroxylation of 25-hydroxyvitamin D3 (250HD3) in vitro. The effect of calcium and phosphate on the rate of synthesis of the product, 1, 25-dihydroxyvitamin D3 (1,25(OH)2D3), was studied at two levels: the long-term effects of various dietary calcium and phosphate contents on the ability of the tubules to produce 1, 25 (OH)2D3, and the acute effects of different calcium and phosphate concentrations in the incubation medium on the rate of synthesis of 1,25(OH)2D3 by the tubules. Manipulation of dietary calcium and phosphate sufficient to produce marked changes in the concentration of calcium and phosphate in the serum led to altered rates of 1,25(OH)2D3 synthesis by the isolated renal tubules. The renal tubules isolated from chicks raised on a vitamin D-deficient diet containing 0.43% calcium and 0.3% P as inorganic phosphate showed the highest rate of synthesis of 1,25(OH)2D3. Diets containing more or less of either calcium or phosphate produced chicks whose renal tubules had a slower rate of 1,25(OH)2D3 production. The calcium, phosphate, and hydrogen ion content of the incubation medium were manipulated to determine the possible factors concerned with the immediate regulation of 1,25(OH)2D3 production. A calcium concentration of 0.5-1.0 mM was necessary for optimal enzymatic activity. Concentrations of calcium greater than this optimal concentration inhibited 1,25(OH)2D3 production if phosphate was also present, and this inhibition was more pronounced as the phosphate concentration was increased. The stimulation of 1,25(OH)2D3 production by calcium was less at pH 6.7 than at 7.4. Raising the phosphate concentration from 0 to 6 mM in the absence of calcium also stimulated the rate of synthesis of 1,25(OH)2D3. This stimulatory effect was blocked by 4 mM calcium. However, at 1-2 mM calciu, phosphate had a biphasic influence on 1,25(OH)2D3 production; extracellular concentrations of phosphate from 0.6 to 1.2 mM resulted in less 1,25(OH)2D3 production than higher or lower phosphate concentrations. This biphasic effect was seen both at pH 7.4 and 6.8."}
{"id": "PMID:236327", "title": "The ionic control of 1,25-dihydroxyvitamin D3 synthesis in isolated chick renal mitochondria. The role of calcium as influenced by inorganic phosphate and hydrogen-ion.", "content": "Isolated kidney mitochondria prepared from Vitamin D-deficient chicks catalyze the conversion of 25-hydroxyvitamin D3 to 1,25 dihydroxyvitamin D3. It wasfound that changes in the concentrations of Ca-2plus, HPO4-2minus, and Hplus altered synthesis in an interrelated fashion. Increasing the Ca-2plus concentration from 10-6 to 10-5 M caused a four- to fivefold increase in 1 alpha-hydroxylase activity when the medium pH was between 6.5 and 7.0. increasing the [Ca2+] to 10-4 M caused to furhter stimulation. At higher pH values, Ca-2plus had little effect upon 1 alpha-hydroxylase activity. In the absence of calcium [Ca2+] less than or equal to 10-7 M), a change in pH from 6.5 to 7.1 had no effect upon 1 alpha-hydroxylase activity in the presence of 10-5 M calcium, increasing the medium pH had a biphasic effect. An increase in pH from 6.5 to 6.9 caused a 1.5-fold increase in 1 alpha-hydroxylase activity, but a further increase of the pH to 7.1 caused a profound decrease in rate of hydroxylation to approximately 20% of the peak value. Neither 10-5 M LaC13 nor 10 mug/ml of oligomycin altered the effects of Ca2+ upon hydroxylate activity. However, the effect of calcium was blocked by 2.5 times 10-5 M ruthenium red, 0.83 mug/ml of antimycin A, and 500 muM dinitrophenol. The clcium ionophore, A23187, decreased but did not prevent the stimulatory effect of calcium. These data are consistent with the concept that the [Ca2+ in the mitochondrial matrix space is of importance in regulating the 1 alpha-hydroxylase. Phosphate exerted a biphasic effect on 1,25(OH)2D3 production with maximal stimulation (approximately twofold) at 1-3 mM. Calcium enhanced the stimulation by phosphate at all concentrations studied. The presence of potassium modified the interrelated effects of calcium and phosphate in two ways: 10-3 M calcium blocked the stimulation by phosphate; and in the presence of phosphate, 10-3 M calcium resulted in less 1,25(OH)2D3 production by production by isolated mitochondria are qualitatively similar to the effects of these ions on 1,25(OH)2D3 production yb isolated renal tubules.", "contents": "The ionic control of 1,25-dihydroxyvitamin D3 synthesis in isolated chick renal mitochondria. The role of calcium as influenced by inorganic phosphate and hydrogen-ion. Isolated kidney mitochondria prepared from Vitamin D-deficient chicks catalyze the conversion of 25-hydroxyvitamin D3 to 1,25 dihydroxyvitamin D3. It wasfound that changes in the concentrations of Ca-2plus, HPO4-2minus, and Hplus altered synthesis in an interrelated fashion. Increasing the Ca-2plus concentration from 10-6 to 10-5 M caused a four- to fivefold increase in 1 alpha-hydroxylase activity when the medium pH was between 6.5 and 7.0. increasing the [Ca2+] to 10-4 M caused to furhter stimulation. At higher pH values, Ca-2plus had little effect upon 1 alpha-hydroxylase activity. In the absence of calcium [Ca2+] less than or equal to 10-7 M), a change in pH from 6.5 to 7.1 had no effect upon 1 alpha-hydroxylase activity in the presence of 10-5 M calcium, increasing the medium pH had a biphasic effect. An increase in pH from 6.5 to 6.9 caused a 1.5-fold increase in 1 alpha-hydroxylase activity, but a further increase of the pH to 7.1 caused a profound decrease in rate of hydroxylation to approximately 20% of the peak value. Neither 10-5 M LaC13 nor 10 mug/ml of oligomycin altered the effects of Ca2+ upon hydroxylate activity. However, the effect of calcium was blocked by 2.5 times 10-5 M ruthenium red, 0.83 mug/ml of antimycin A, and 500 muM dinitrophenol. The clcium ionophore, A23187, decreased but did not prevent the stimulatory effect of calcium. These data are consistent with the concept that the [Ca2+ in the mitochondrial matrix space is of importance in regulating the 1 alpha-hydroxylase. Phosphate exerted a biphasic effect on 1,25(OH)2D3 production with maximal stimulation (approximately twofold) at 1-3 mM. Calcium enhanced the stimulation by phosphate at all concentrations studied. The presence of potassium modified the interrelated effects of calcium and phosphate in two ways: 10-3 M calcium blocked the stimulation by phosphate; and in the presence of phosphate, 10-3 M calcium resulted in less 1,25(OH)2D3 production by production by isolated mitochondria are qualitatively similar to the effects of these ions on 1,25(OH)2D3 production yb isolated renal tubules."}
{"id": "PMID:236328", "title": "The mechanism of the natriuresis of fasting.", "content": "This study tests the hypothesis than obligatory cation coverage of metabolicaly generated anions is the mechanism for the sodium diuresis of fasting. Nine obese female subjects were equilibrated on a constant sodium and caloric intake and then fasted while sodium intake was maintianed. Particular activity schedule during fasting as during control. Consecutive 3-h increases in urinary sodium , ammonium, and potassium excretion during fasting were matched against simultaneously determined increases in organic acid anions (OAS) and H2PO4 minus, which would exist in combination with the cations. The changes were significantly correlated (r equals 0.891, P less than 0.001) in the relationship y equals 0.73x plus 19 where y equals increases in organic acid salts plus H2POJ minus and x equals increases in cations. As ammonium excretion rose, sodium conservation occurred with ammonium replacing sodium at the major urinary cation. Corollaries to the hypothesis were also found to be true. They were: (a) Increases in ammonium excretion lagged considerably behind increases in OAS plus H2PO4 minus during the diuretic phase making sodium coverage necessary. (b) Sodium loss was much greater than chloride although chloride balance was minimally negative. (c) After refeeding with glucose, sodium excretion promptly decreased and appeared best correlated with simultaneous decreases in OAS. Ammonium excretion also fell but much less than sodium. The data support the hypothesis that obligatory cation coverage of metabolically generated aniuns is a major mechanism responsible for the sodium diuresis of fasting.", "contents": "The mechanism of the natriuresis of fasting. This study tests the hypothesis than obligatory cation coverage of metabolicaly generated anions is the mechanism for the sodium diuresis of fasting. Nine obese female subjects were equilibrated on a constant sodium and caloric intake and then fasted while sodium intake was maintianed. Particular activity schedule during fasting as during control. Consecutive 3-h increases in urinary sodium , ammonium, and potassium excretion during fasting were matched against simultaneously determined increases in organic acid anions (OAS) and H2PO4 minus, which would exist in combination with the cations. The changes were significantly correlated (r equals 0.891, P less than 0.001) in the relationship y equals 0.73x plus 19 where y equals increases in organic acid salts plus H2POJ minus and x equals increases in cations. As ammonium excretion rose, sodium conservation occurred with ammonium replacing sodium at the major urinary cation. Corollaries to the hypothesis were also found to be true. They were: (a) Increases in ammonium excretion lagged considerably behind increases in OAS plus H2PO4 minus during the diuretic phase making sodium coverage necessary. (b) Sodium loss was much greater than chloride although chloride balance was minimally negative. (c) After refeeding with glucose, sodium excretion promptly decreased and appeared best correlated with simultaneous decreases in OAS. Ammonium excretion also fell but much less than sodium. The data support the hypothesis that obligatory cation coverage of metabolically generated aniuns is a major mechanism responsible for the sodium diuresis of fasting."}
{"id": "PMID:236329", "title": "The effect of anemia on the ventilatory response to transient and steady-state hypoxia.", "content": "The effects of anemia upon the ventilatory responses to transient and steady-state hypoxia were studied in unanesthetized goats. Responses to transient hypoxia (inhalation of several breaths of nitrogen) were considered to reflect peripheral chemoreceptor and non-chemoreceptor influences of hypoxia upon ventilatory control. In all goats, severe anemia (hemoglobin 3.1-4.8 g/100ml) markedly heightened the responses to transient hypoxia (from a mean of 0.27 to a mean of 0.75 liter/min/percent fall in SaO2). This phenomenon was substantially reversed by alpha-adrenergic blockade (phenoxybenzamine, 5 mg/kg). In contrast, the ventilatory responses to steady-state hypoxia were unaffected by severe anemia. These data suggest that severe anemia enhances the peripheral chemoreceptor-mediated response to hypoxia through a mechanism involving the alpha-adrenergic system. It also appears that a ventilatory depressant effect of hypoxia which is not mediated by the peripheral chemoreceptors is also enhanced by severe anemia, thereby preventing an increase in the steady-state ventilatory response to hypoxia. Finally, experiments involving variation in oxygen affinity of hemoglobin suggested that O2 tension rather than O2 availability in arterial blood is the major determinant of peripheral chemoreceptor activity.", "contents": "The effect of anemia on the ventilatory response to transient and steady-state hypoxia. The effects of anemia upon the ventilatory responses to transient and steady-state hypoxia were studied in unanesthetized goats. Responses to transient hypoxia (inhalation of several breaths of nitrogen) were considered to reflect peripheral chemoreceptor and non-chemoreceptor influences of hypoxia upon ventilatory control. In all goats, severe anemia (hemoglobin 3.1-4.8 g/100ml) markedly heightened the responses to transient hypoxia (from a mean of 0.27 to a mean of 0.75 liter/min/percent fall in SaO2). This phenomenon was substantially reversed by alpha-adrenergic blockade (phenoxybenzamine, 5 mg/kg). In contrast, the ventilatory responses to steady-state hypoxia were unaffected by severe anemia. These data suggest that severe anemia enhances the peripheral chemoreceptor-mediated response to hypoxia through a mechanism involving the alpha-adrenergic system. It also appears that a ventilatory depressant effect of hypoxia which is not mediated by the peripheral chemoreceptors is also enhanced by severe anemia, thereby preventing an increase in the steady-state ventilatory response to hypoxia. Finally, experiments involving variation in oxygen affinity of hemoglobin suggested that O2 tension rather than O2 availability in arterial blood is the major determinant of peripheral chemoreceptor activity."}
{"id": "PMID:236330", "title": "Pneumococcal antigen in lobar pneumonia.", "content": "This paper describes the value in diagnosis and the clinical implications of the detection of pneumococcal antigen in patients with lobar pneumonia. Ninety-eight patients with lobar pneumonia were investigated. Pneumococcal antigen was detected by counter-current immunoelectrophoresis in the sputum of 79% of patients with purulent sputum, in the serum of 29% of the patients, and in the urine of 54% of the patients. The diagnostic value of counter-current immunoelectrophoresis was not affected by prior antibiotic therapy. Patients with antigenaemia had a higher incidence of complications than those without as shown by an association between antigenaemia and jaundice, diarrhoea, and persistent pyrexia. Antigen persisted in the circulation for at least seven days in half the patients studied, possibly indicating the development of immunological tolerance to the polysaccharide antigen.", "contents": "Pneumococcal antigen in lobar pneumonia. This paper describes the value in diagnosis and the clinical implications of the detection of pneumococcal antigen in patients with lobar pneumonia. Ninety-eight patients with lobar pneumonia were investigated. Pneumococcal antigen was detected by counter-current immunoelectrophoresis in the sputum of 79% of patients with purulent sputum, in the serum of 29% of the patients, and in the urine of 54% of the patients. The diagnostic value of counter-current immunoelectrophoresis was not affected by prior antibiotic therapy. Patients with antigenaemia had a higher incidence of complications than those without as shown by an association between antigenaemia and jaundice, diarrhoea, and persistent pyrexia. Antigen persisted in the circulation for at least seven days in half the patients studied, possibly indicating the development of immunological tolerance to the polysaccharide antigen."}
{"id": "PMID:236331", "title": "A new method for the assay of factor XI in plasma and the preparation and use of a new artificial substrate.", "content": "An improved method for the one-stage assay of factor XI in plasma has been proposed; it is reproducible and compares well with an old, established method.A short investigation into the preparation and use of artificially prepared factor XI-deficient plasma has been carried out: this substrate can be used as an alternative to the congenitally deficient substrate.", "contents": "A new method for the assay of factor XI in plasma and the preparation and use of a new artificial substrate. An improved method for the one-stage assay of factor XI in plasma has been proposed; it is reproducible and compares well with an old, established method.A short investigation into the preparation and use of artificially prepared factor XI-deficient plasma has been carried out: this substrate can be used as an alternative to the congenitally deficient substrate."}
{"id": "PMID:236332", "title": "The effect of angiotensin on myocardial contractility.", "content": "Previous studies of the effect of angiotensin on myocardial contractility have yielded conflicting results. Possible reasons for the observed disparities include differences in techniques for measuring contractility, in species (dog, cat, and man), in myocardial state (normal or diseased), in preparation observed (heart-lung, isolated heart, papillary muscle, atrial myocardium, intact heart), and in dosage schedule. Moreover, there are no reported studies in the intact human heart, normal or diseased, in which contractility measurements are based on velocity-force relations. To resolve the conflict, left ventricular myocardial contractility was measured using the same expressions for the force-velocity relationship in all subjects. Studies were performed in five normal human subjects, six patients with cardiomyopathy, eight normal mongrel dogs, and six dogs with ischemic myocardial scarring, before and during angiotensin infusions in dosages producing 15--20-mm Hg increases of aortic diastolic pressure. Contractile element velocity at peak, dP/dt (Vce) and the Frank-Levinson contractility index (CyIx), which normalizes Vce for diastolic fiber length, decreased during angiotensin infusion in all groups. The mean decreases (11 to 19) per cent in Vce, 15 to 23 per cent in CyIx, SEM's 4-5 per cent) were significant (P values ranging from smaller than 0.05 to smaller 0.005) in the normal hearts of dogs and man and in the scarred canine hearts, in which preangiotensin Vce and CyIx were normal. In the cardiomyopathy group, in which contractility was depressed before angiotensin, the drug elicited a further decrease in Vce (mean fall 17 plus or minus 7 per cent, P smaller than 0.1) and CyIx (26 plus or minus 8 per cent,  P smaller than 0.02). We conclude that, in the intact organism, with a normal myocardium or a diffuse or segmental myocardial disease, the administration of angiotensin results in a depression of contractility.", "contents": "The effect of angiotensin on myocardial contractility. Previous studies of the effect of angiotensin on myocardial contractility have yielded conflicting results. Possible reasons for the observed disparities include differences in techniques for measuring contractility, in species (dog, cat, and man), in myocardial state (normal or diseased), in preparation observed (heart-lung, isolated heart, papillary muscle, atrial myocardium, intact heart), and in dosage schedule. Moreover, there are no reported studies in the intact human heart, normal or diseased, in which contractility measurements are based on velocity-force relations. To resolve the conflict, left ventricular myocardial contractility was measured using the same expressions for the force-velocity relationship in all subjects. Studies were performed in five normal human subjects, six patients with cardiomyopathy, eight normal mongrel dogs, and six dogs with ischemic myocardial scarring, before and during angiotensin infusions in dosages producing 15--20-mm Hg increases of aortic diastolic pressure. Contractile element velocity at peak, dP/dt (Vce) and the Frank-Levinson contractility index (CyIx), which normalizes Vce for diastolic fiber length, decreased during angiotensin infusion in all groups. The mean decreases (11 to 19) per cent in Vce, 15 to 23 per cent in CyIx, SEM's 4-5 per cent) were significant (P values ranging from smaller than 0.05 to smaller 0.005) in the normal hearts of dogs and man and in the scarred canine hearts, in which preangiotensin Vce and CyIx were normal. In the cardiomyopathy group, in which contractility was depressed before angiotensin, the drug elicited a further decrease in Vce (mean fall 17 plus or minus 7 per cent, P smaller than 0.1) and CyIx (26 plus or minus 8 per cent,  P smaller than 0.02). We conclude that, in the intact organism, with a normal myocardium or a diffuse or segmental myocardial disease, the administration of angiotensin results in a depression of contractility."}
{"id": "PMID:236333", "title": "Fungal growth and acid production during fermentation and refermentation of organic acid treated corn silages.", "content": "Chopped corn (35% dry matter) treated with either propionic, formic, 60% propionic plus 40% formic, or 80% propionic plus 20% acetic acids at 0, .5, 1, and 2%, was placed in polyethylene bags inside metal drums, and evacuated. During fermentation silages were sampled and temperatures determined. On day 40 of fermentation silages were placed in open containers at 25 C and were sampled during refermentation. All samples were analyzed for volatile and lactic acids, pH, and number and type of fungi. Lactate fermentation was totally inhibited at 2% addition of all acids, but formic acid was more effective than propionic acid at .5 and 1%. Acerate production was equally depressed by both propionic and formic additions. Heating, growth of fungi, and days until spoilage were delayed by all acid additions during refermentation, with propionic more effectivethan formic. The large increases in lactate and acetate of treated silages during refermentation reflect a protection of soluble sugars during fermentation and subsequent use by microbes after exposure to air. Silages treated with more than 1%propionic (as propionic or a mixture) did not increase in fungal colonies during refermentation. At initiation of fermentation yeasts werehigher than other fungi but decreases by day 40. During refermentation, yeasts again grew. Geotrichum comprised 35% on day 40 of refermentation but was lower at other times. Aspergillus proliferated during refermentation and few Penicillium were detected.", "contents": "Fungal growth and acid production during fermentation and refermentation of organic acid treated corn silages. Chopped corn (35% dry matter) treated with either propionic, formic, 60% propionic plus 40% formic, or 80% propionic plus 20% acetic acids at 0, .5, 1, and 2%, was placed in polyethylene bags inside metal drums, and evacuated. During fermentation silages were sampled and temperatures determined. On day 40 of fermentation silages were placed in open containers at 25 C and were sampled during refermentation. All samples were analyzed for volatile and lactic acids, pH, and number and type of fungi. Lactate fermentation was totally inhibited at 2% addition of all acids, but formic acid was more effective than propionic acid at .5 and 1%. Acerate production was equally depressed by both propionic and formic additions. Heating, growth of fungi, and days until spoilage were delayed by all acid additions during refermentation, with propionic more effectivethan formic. The large increases in lactate and acetate of treated silages during refermentation reflect a protection of soluble sugars during fermentation and subsequent use by microbes after exposure to air. Silages treated with more than 1%propionic (as propionic or a mixture) did not increase in fungal colonies during refermentation. At initiation of fermentation yeasts werehigher than other fungi but decreases by day 40. During refermentation, yeasts again grew. Geotrichum comprised 35% on day 40 of refermentation but was lower at other times. Aspergillus proliferated during refermentation and few Penicillium were detected."}
{"id": "PMID:236337", "title": "Psychopharmacologic investigations in healthy elderly volunteers: effects of pipradrol-vitamin (Alertonic) elixir and placebo in relation to research design.", "content": "Ninety-nine healthy elderly volunteers were tested to assess the effects of: 1) a pipradrol-vitamin (Alertonic) elixir, 2) a placebo, and 3) no treatment, during a one-week period.  The assessment measures were the Minnesota Multiphasic Personality Inventory Depression Scale, the Zung Depression Scale, Profile of Mood States, and the WAIS Digit Span.  Alertonic had no sigmificant effects on mood, memory or appetite, and the placebo effect was rarely greater than 50 per cent.  There were no significant side effects.  The findings demonstrate a valid method for studying psychotropic agents in the elderly.", "contents": "Psychopharmacologic investigations in healthy elderly volunteers: effects of pipradrol-vitamin (Alertonic) elixir and placebo in relation to research design. Ninety-nine healthy elderly volunteers were tested to assess the effects of: 1) a pipradrol-vitamin (Alertonic) elixir, 2) a placebo, and 3) no treatment, during a one-week period.  The assessment measures were the Minnesota Multiphasic Personality Inventory Depression Scale, the Zung Depression Scale, Profile of Mood States, and the WAIS Digit Span.  Alertonic had no sigmificant effects on mood, memory or appetite, and the placebo effect was rarely greater than 50 per cent.  There were no significant side effects.  The findings demonstrate a valid method for studying psychotropic agents in the elderly."}
{"id": "PMID:236339", "title": "Diagnosis of Schistosoma bovis infection in cattle by an indirect haemagglutination test.", "content": "An indirect haemagglutination test has been developed for the detection of Schistosoma bovis antibody. Fresh, formalin and glutaraldehyde fixed sheep erythrocytes as well as fresh and formalin fixed human erythrocytes were tested. Tanned glutaraldehyde fixed sheep erythrocytes sensitized with an adult worm extract were the most sensitive and remained stable for at least 8 weeks at 4 degrees C. With such cells 98% of a group of S. bovis infected cattle were positive while negative results were obtained from cattle infected with other helminths.", "contents": "Diagnosis of Schistosoma bovis infection in cattle by an indirect haemagglutination test. An indirect haemagglutination test has been developed for the detection of Schistosoma bovis antibody. Fresh, formalin and glutaraldehyde fixed sheep erythrocytes as well as fresh and formalin fixed human erythrocytes were tested. Tanned glutaraldehyde fixed sheep erythrocytes sensitized with an adult worm extract were the most sensitive and remained stable for at least 8 weeks at 4 degrees C. With such cells 98% of a group of S. bovis infected cattle were positive while negative results were obtained from cattle infected with other helminths."}
{"id": "PMID:236340", "title": "Colloidal alpha-stannic acid and negative iron colloid as differential electron stains for surface proteins.", "content": "Colloidal alpha-stannic acid and a negative iron colloid obtained from ferric hydroxide and potassium ferrocyanide, both negative sols being stable within a wide pH range, were refined as surface protein electron markers. Because of the relatively small size of its particles, colloidal alpha-stannic acid was used for staining all surface proteins. According to the pH at which the negative iron colloid was applied, it revealed either all surface proteins, or because of its large colloidal particles, stained basic proteins. This differential staining capability of the iron colloidal has been demonstrated previously on various control preparations (Puvion E, Blanquet PR: J Microsc 12:171, 1971). Controls on the affinity of the two colloids to surface amino groups were carried out on rat liver, mouse fibroblasts, HeLa and KB cells, Ehrlich and Zajdela ascites cells subjected to prior enzymatic and chemical treatments (incubation with neuraminidase or phospholipase C, esterification, acetylation or lipid extraction). At any pH below 9, the two sols stained proteins in the outer hydrophilic leaflet of esterified cells with relative selectivity, but the alpha-stannic acid showed them more accurately. The iron sol did reveal at high pH protein components of high isoionic point on the surfaces of rat hepatocytes and ascites cells which had only been treated with neuraminidase.", "contents": "Colloidal alpha-stannic acid and negative iron colloid as differential electron stains for surface proteins. Colloidal alpha-stannic acid and a negative iron colloid obtained from ferric hydroxide and potassium ferrocyanide, both negative sols being stable within a wide pH range, were refined as surface protein electron markers. Because of the relatively small size of its particles, colloidal alpha-stannic acid was used for staining all surface proteins. According to the pH at which the negative iron colloid was applied, it revealed either all surface proteins, or because of its large colloidal particles, stained basic proteins. This differential staining capability of the iron colloidal has been demonstrated previously on various control preparations (Puvion E, Blanquet PR: J Microsc 12:171, 1971). Controls on the affinity of the two colloids to surface amino groups were carried out on rat liver, mouse fibroblasts, HeLa and KB cells, Ehrlich and Zajdela ascites cells subjected to prior enzymatic and chemical treatments (incubation with neuraminidase or phospholipase C, esterification, acetylation or lipid extraction). At any pH below 9, the two sols stained proteins in the outer hydrophilic leaflet of esterified cells with relative selectivity, but the alpha-stannic acid showed them more accurately. The iron sol did reveal at high pH protein components of high isoionic point on the surfaces of rat hepatocytes and ascites cells which had only been treated with neuraminidase."}
{"id": "PMID:236341", "title": "The ultrastructural cytochemistry of lactic dehydrogenase, succinic dehydrogenase, dihydro-nicotinamide adenine dinucleotide diaphorase and cytochrome oxidase activities in hair cell mitochondria of the guinea pig cochlea.", "content": "The use of cinnamyl nitroblue tetrazolium chloride (DS-NBT) in dehydrogenase experiments (lactic dehydrogenase, succinic dehydrogenase, nicotinamide adenine dinucleotide diaphorase) and 3,3'-diaminobenzidine tetrahydrochloride (DAB) in cytochrome oxidase experiments indicated that mitochondrial oxidoreduction reactions from nicotinamide adenine dinucleotide to cytochrome oxidase are located on the inner mitochondrial membrane in the outer compartment and the intracristate spaces. These reactions behave according to the chemiosmotic hypothesis. The cochlear hair cell mitochondria are cytochemically indistinguishable from free liver mitochondria. The heterogeneous mitochondrial staining pattern is related to the osmolarity of the incubation media, solubility of the enzymes and pH of the medium, but not to the fixation method.", "contents": "The ultrastructural cytochemistry of lactic dehydrogenase, succinic dehydrogenase, dihydro-nicotinamide adenine dinucleotide diaphorase and cytochrome oxidase activities in hair cell mitochondria of the guinea pig cochlea. The use of cinnamyl nitroblue tetrazolium chloride (DS-NBT) in dehydrogenase experiments (lactic dehydrogenase, succinic dehydrogenase, nicotinamide adenine dinucleotide diaphorase) and 3,3'-diaminobenzidine tetrahydrochloride (DAB) in cytochrome oxidase experiments indicated that mitochondrial oxidoreduction reactions from nicotinamide adenine dinucleotide to cytochrome oxidase are located on the inner mitochondrial membrane in the outer compartment and the intracristate spaces. These reactions behave according to the chemiosmotic hypothesis. The cochlear hair cell mitochondria are cytochemically indistinguishable from free liver mitochondria. The heterogeneous mitochondrial staining pattern is related to the osmolarity of the incubation media, solubility of the enzymes and pH of the medium, but not to the fixation method."}
{"id": "PMID:236342", "title": "Immunobiological biochemical and physico-chemical characteristics of Brucella lipopolysaccharide subjected to various doses of gamma radiation.", "content": "A comparative study of toxicity, serological activity, some biochemical and physico-chemical properties of the highly toxic Brucella lipopolysaccharide (LPS) and of preparations obtained after the action of gamma radiation in doses of 1.3 and 10 mrad on the antigen. The toxicity of LPS was found to decrease with the increasing dose of irradiation. Irradiation with a dose of 3 mrad produced a marked decrease in the toxicity of the antigen without causing essential changes in its serological properties. The process of LPS detoxication under the effect of irradiation was accompanied by changes in certain biochemical and physico-chemical indices suggestive of the modification of the primary structure of the LPS molecule and of impairment of mainly its polysaccharide side chains.", "contents": "Immunobiological biochemical and physico-chemical characteristics of Brucella lipopolysaccharide subjected to various doses of gamma radiation. A comparative study of toxicity, serological activity, some biochemical and physico-chemical properties of the highly toxic Brucella lipopolysaccharide (LPS) and of preparations obtained after the action of gamma radiation in doses of 1.3 and 10 mrad on the antigen. The toxicity of LPS was found to decrease with the increasing dose of irradiation. Irradiation with a dose of 3 mrad produced a marked decrease in the toxicity of the antigen without causing essential changes in its serological properties. The process of LPS detoxication under the effect of irradiation was accompanied by changes in certain biochemical and physico-chemical indices suggestive of the modification of the primary structure of the LPS molecule and of impairment of mainly its polysaccharide side chains."}
{"id": "PMID:236343", "title": "Nationwide epidemic of septicemia caused by contaminated infusion products. IV. Growth of microbial pathogens in fluids for intravenous infusions.", "content": "Septicemia caused by contaminated infusion fluid is a newly appreciated hazard of intravenous infusion therapy. Microorganisms of the tribe Klebsielleae (Klebsiella, Enterobacter, and Serratia) have predominated in these infections. Members of this tribe found to possess a selecive ability over common non-Klebsielleae microbial pathogens to proliferate rapidly in commerical parential fluids contaning clucose at room temperautre. Fifty-one Klebsielleae strains, washed twice before inoculation of approximately 1 organism/ml, attained a mean normalized 24 hr concentration of 1.11 x 10-5 organisms/ml in 5% dextrose in water at 25 C. In contrast, 48 of 49 non-Klebsielleae bacterial strains (clinical isolates of Staphylococcus, Proteus, Escherichia coli, Herelea, and Pseudomonas aeruginosa) slowly died (mean 24-hr concentration, 0.2 organism/ml). Five Candida albicans strains frew only very slowly (31.3 organisms/ml). Even with concentrations exceeding 10-6 organisms/ml, microbial presence was never visibly detectable. The significant increases in cases of nosocomial spticmia caused by Klebsiella, Enterobacter, and Serratia in recent years might be attribuatble in part to fluid-related spesis accompanying the expanding use of parenteral therapy.", "contents": "Nationwide epidemic of septicemia caused by contaminated infusion products. IV. Growth of microbial pathogens in fluids for intravenous infusions. Septicemia caused by contaminated infusion fluid is a newly appreciated hazard of intravenous infusion therapy. Microorganisms of the tribe Klebsielleae (Klebsiella, Enterobacter, and Serratia) have predominated in these infections. Members of this tribe found to possess a selecive ability over common non-Klebsielleae microbial pathogens to proliferate rapidly in commerical parential fluids contaning clucose at room temperautre. Fifty-one Klebsielleae strains, washed twice before inoculation of approximately 1 organism/ml, attained a mean normalized 24 hr concentration of 1.11 x 10-5 organisms/ml in 5% dextrose in water at 25 C. In contrast, 48 of 49 non-Klebsielleae bacterial strains (clinical isolates of Staphylococcus, Proteus, Escherichia coli, Herelea, and Pseudomonas aeruginosa) slowly died (mean 24-hr concentration, 0.2 organism/ml). Five Candida albicans strains frew only very slowly (31.3 organisms/ml). Even with concentrations exceeding 10-6 organisms/ml, microbial presence was never visibly detectable. The significant increases in cases of nosocomial spticmia caused by Klebsiella, Enterobacter, and Serratia in recent years might be attribuatble in part to fluid-related spesis accompanying the expanding use of parenteral therapy."}
{"id": "PMID:236345", "title": "Immunogenicity of formaldehyde-inactivated enterotoxins A and C1 of Staphylococcus aureus.", "content": "Quantitative precipitation of antisera specific for native enterotoxin revealed that 70% and 60%, respectively, of the antigenic determinants of enterotoxins A and C1 of Staphylococcus aureus were inactivated by formaldehyde at pH 5.0 or 7.5 contained large polymers (excluded by Sepharose 2B) and induced strong humoral immune responses in rhesus monkeys. Enterotoxin A inactivated at pH 5.0 or 7.5 was composed mostly of small polymers (excluded by Sephadex G-100 but included by Sepharose 2B); it provoked a poor immune response in monkeys (about equivalent to the response obtained with weakly reactive toxin inactivated at alkaline pH). It was concluded that potent enterotoxoids were formed by extensive cross-linking of enterotoxin C1 into large polymers in acidic or neutral formaldehyde solution.", "contents": "Immunogenicity of formaldehyde-inactivated enterotoxins A and C1 of Staphylococcus aureus. Quantitative precipitation of antisera specific for native enterotoxin revealed that 70% and 60%, respectively, of the antigenic determinants of enterotoxins A and C1 of Staphylococcus aureus were inactivated by formaldehyde at pH 5.0 or 7.5 contained large polymers (excluded by Sepharose 2B) and induced strong humoral immune responses in rhesus monkeys. Enterotoxin A inactivated at pH 5.0 or 7.5 was composed mostly of small polymers (excluded by Sephadex G-100 but included by Sepharose 2B); it provoked a poor immune response in monkeys (about equivalent to the response obtained with weakly reactive toxin inactivated at alkaline pH). It was concluded that potent enterotoxoids were formed by extensive cross-linking of enterotoxin C1 into large polymers in acidic or neutral formaldehyde solution."}
{"id": "PMID:236346", "title": "The pathogenesis of Shigella diarrhea. V. Relationship of shiga enterotoxin, neurotoxin, and cytotoxin.", "content": "The biological activity of the enterotoxin of Shigella dysenteriae 1 was compared with that of a well-studied 20-year-old partially purified preparation of neurotoxin from the same organism. Enterotoxicity, neurotoxicity, and cytotoxicity were present to an equivalent extent in both preparations. Human convalescent antisera and experimental rabbit antisera had equal toxin-neutralizing antibody to the cytotoxic activity in these toxin preparations. Multiple protein bands were present in each toxin studied. Two separate HeLa cell fractions could be obtained by Sephadex gel filtration chromatography, isoelectric focusing in a sucrose gradient, and polyacrylamide gel electrophoresis. Only one of these fractions (isoelectric at pH 7.2) was associated with enterotoxicity and neurotoxicity. The second smaller-molecular-weight fraction, which was isoelectric at pH 6.1, possessed only cytotoxic activity. These data suggest that Shiga enterotoxin and neurotoxin are closely related proteins and, indeed, may be identical. The nature of the cytotoxin with pH 6.1 is not clear, although it may be a subunit of the larger toxin that is capable of acting directly on the HeLa cell.", "contents": "The pathogenesis of Shigella diarrhea. V. Relationship of shiga enterotoxin, neurotoxin, and cytotoxin. The biological activity of the enterotoxin of Shigella dysenteriae 1 was compared with that of a well-studied 20-year-old partially purified preparation of neurotoxin from the same organism. Enterotoxicity, neurotoxicity, and cytotoxicity were present to an equivalent extent in both preparations. Human convalescent antisera and experimental rabbit antisera had equal toxin-neutralizing antibody to the cytotoxic activity in these toxin preparations. Multiple protein bands were present in each toxin studied. Two separate HeLa cell fractions could be obtained by Sephadex gel filtration chromatography, isoelectric focusing in a sucrose gradient, and polyacrylamide gel electrophoresis. Only one of these fractions (isoelectric at pH 7.2) was associated with enterotoxicity and neurotoxicity. The second smaller-molecular-weight fraction, which was isoelectric at pH 6.1, possessed only cytotoxic activity. These data suggest that Shiga enterotoxin and neurotoxin are closely related proteins and, indeed, may be identical. The nature of the cytotoxin with pH 6.1 is not clear, although it may be a subunit of the larger toxin that is capable of acting directly on the HeLa cell."}
{"id": "PMID:236350", "title": "Control of sterol synthesis and of hydroxymethylglutaryl CoA reductase in skin fibroblasts grown from patients with homozygous type II hyperlipoproteinemia.", "content": "In skin fibroblasts grown from four children with a homozygous form of type II hyperlipoproteinemia, the feedback control of sterol synthesis and the inhibitory effect on hydroxymethylglutaryl (HMG) CoA reductase activity by serum or low density lipoprotein were present, though diminished compared with the effects in normal fibroblasts. Stimulation of HMG CoA reductase by insulin and inhibition of acetyl CoA carboxylase by serum lipids were not impaired in these type II cells, indicating a degree of specificity in the abnormal response of the reductase. A rapid and convenient method for isolation of mevalonolactone in the course of the assay of HMG CoA reductase is described.", "contents": "Control of sterol synthesis and of hydroxymethylglutaryl CoA reductase in skin fibroblasts grown from patients with homozygous type II hyperlipoproteinemia. In skin fibroblasts grown from four children with a homozygous form of type II hyperlipoproteinemia, the feedback control of sterol synthesis and the inhibitory effect on hydroxymethylglutaryl (HMG) CoA reductase activity by serum or low density lipoprotein were present, though diminished compared with the effects in normal fibroblasts. Stimulation of HMG CoA reductase by insulin and inhibition of acetyl CoA carboxylase by serum lipids were not impaired in these type II cells, indicating a degree of specificity in the abnormal response of the reductase. A rapid and convenient method for isolation of mevalonolactone in the course of the assay of HMG CoA reductase is described."}
{"id": "PMID:236351", "title": "Fatty acid binding to plasma albumin.", "content": "A review of the available information about fatty acid binding to plasma albumin is presented. Albumin is composed of a single polypeptide chain, folded so as to form three or four spherical units. The strong fatty acid binding sites probably are located in crevices between these spherical regions. The anionic form of the fatty acid binds to albumin. Most of the binding energy comes from nonpolar interactions between the fatty acid hydrocarbon chain and uncharged amino acid side chains that line the binding sites. The binding sites are somewhat pliable, and their configuration can adapt to fit the incoming fatty acid. Stepwise association constants for binding to human albumin of fatty acids containing 6-18 carbon atoms are presented. These data indicate that each mole of fatty acid binds with a different affinity and that the association constants for multiple binding diminish sequentially, i.e., kappa 1 greater than kappa 2 greater than kappa 3 greater ... greater kappan. Because of uncertainties concerning fatty acid association in aqueous solutions, the constants for the 14-18 carbon acids probably are not definitive. In the usual physiological concentration range, free fatty acids do not displace appreciable amounts of a second organic compound from albumin. Sensitive spectrophotometric analyses revealed, however, that even small increases in free fatty acid concentration alter the molecular interaction between human albumin and another organic compound.", "contents": "Fatty acid binding to plasma albumin. A review of the available information about fatty acid binding to plasma albumin is presented. Albumin is composed of a single polypeptide chain, folded so as to form three or four spherical units. The strong fatty acid binding sites probably are located in crevices between these spherical regions. The anionic form of the fatty acid binds to albumin. Most of the binding energy comes from nonpolar interactions between the fatty acid hydrocarbon chain and uncharged amino acid side chains that line the binding sites. The binding sites are somewhat pliable, and their configuration can adapt to fit the incoming fatty acid. Stepwise association constants for binding to human albumin of fatty acids containing 6-18 carbon atoms are presented. These data indicate that each mole of fatty acid binds with a different affinity and that the association constants for multiple binding diminish sequentially, i.e., kappa 1 greater than kappa 2 greater than kappa 3 greater ... greater kappan. Because of uncertainties concerning fatty acid association in aqueous solutions, the constants for the 14-18 carbon acids probably are not definitive. In the usual physiological concentration range, free fatty acids do not displace appreciable amounts of a second organic compound from albumin. Sensitive spectrophotometric analyses revealed, however, that even small increases in free fatty acid concentration alter the molecular interaction between human albumin and another organic compound."}
{"id": "PMID:236352", "title": "Enzymatic synthesis of mannosyl retinyl phosphate from retinyl phosphate and guanosine diphosphate mannose.", "content": "A study was conducted to determine whether retinyl phosphate would act as substrate for the enzymatic synthesis of mannosyl retinyl phosphate. Retinyl phosphate, prepared chemically, supported the growth of vitamin A-deficient rats at the same rate as retinol. It also stimulated the uptake of [14C]mannose from GDP-[14C]mannose into total chloroform-methanol extractable lipid. This reaction occurred in the presence of ATP, Mn2+, detergent (Zonyl A), and a membrane-rich enzyme preparation from the livers of vitamin A-deficient rats, provided that a lipid extract of the membrane preparation of alpha-L-lecithin was also added. Total chloroform-methanol-extractable, labeled mannolipid was separated into two principal labeled mannolipids by thin-layer or column chromatography or by differential solvent extraction. The properties of these mannolipids identified them as glycophospholipids: one was identical with authentic synthetic dolichyl mannosyl phosphate, and the other was concluded to be mannosyl retinyl phosphate because of its incorporation of radioactivity from [3H]retinyl phosphate, its rapid hydrolysis by dilute acid, and the formation of substance that cochromatographed with retinol upon its acid hydrolysis. The presence of ATP or GTP was essential for the stimulation of mannolipid synthesis, probably because of their protective action on the substrates against phosphatases present in the crude enzyme fraction. A pH of 6.0-6.2 favored the formation of dolichyl mannosyl phosphate; a higher pH (6.7-7.0) that of mannosyl retinyl phosphate.", "contents": "Enzymatic synthesis of mannosyl retinyl phosphate from retinyl phosphate and guanosine diphosphate mannose. A study was conducted to determine whether retinyl phosphate would act as substrate for the enzymatic synthesis of mannosyl retinyl phosphate. Retinyl phosphate, prepared chemically, supported the growth of vitamin A-deficient rats at the same rate as retinol. It also stimulated the uptake of [14C]mannose from GDP-[14C]mannose into total chloroform-methanol extractable lipid. This reaction occurred in the presence of ATP, Mn2+, detergent (Zonyl A), and a membrane-rich enzyme preparation from the livers of vitamin A-deficient rats, provided that a lipid extract of the membrane preparation of alpha-L-lecithin was also added. Total chloroform-methanol-extractable, labeled mannolipid was separated into two principal labeled mannolipids by thin-layer or column chromatography or by differential solvent extraction. The properties of these mannolipids identified them as glycophospholipids: one was identical with authentic synthetic dolichyl mannosyl phosphate, and the other was concluded to be mannosyl retinyl phosphate because of its incorporation of radioactivity from [3H]retinyl phosphate, its rapid hydrolysis by dilute acid, and the formation of substance that cochromatographed with retinol upon its acid hydrolysis. The presence of ATP or GTP was essential for the stimulation of mannolipid synthesis, probably because of their protective action on the substrates against phosphatases present in the crude enzyme fraction. A pH of 6.0-6.2 favored the formation of dolichyl mannosyl phosphate; a higher pH (6.7-7.0) that of mannosyl retinyl phosphate."}
{"id": "PMID:236354", "title": "Subcellular localization and heterogeneity of neutral proteases in neutrophilic polymorphonuclear leukocytes.", "content": "The subcellular localization of elastase and of neutral proteases hydrolyzing histone and casein was determined in human and rabbit polymorphonuclear leukocytes using fractionation by isopycnic centrifugation. Granule-rich fractions obtained by this technique were extracted and analyzed by acrylamide gel electrophoresis, and proteolytic activity on the gels was demonstrated by staining with either N-acetyl-D,L-alanine alpha-naphthyl ester or naphthol AS-D acetate as substrate. In both species, all neutral proteases assayed were found to be localized exclusively in the azurophil granules. Specific activities were about 10-30 times higher in human than in rabbit preparations. In extracts of human azurophil granules up to 10 proteins exhibiting esterolytic activity could be demonstrated after electrophoretic separation. Three major and two or three minor components of these esterases were shown to possess elastase activity. Similar zymograms prepared with extracts from rabbit azurophil granules revealed only one major elastase band. The electrophoretic analysis further showed that the most strongly cationic proteins of both human and rabbit PMNs were also confined to the azurophil granules.", "contents": "Subcellular localization and heterogeneity of neutral proteases in neutrophilic polymorphonuclear leukocytes. The subcellular localization of elastase and of neutral proteases hydrolyzing histone and casein was determined in human and rabbit polymorphonuclear leukocytes using fractionation by isopycnic centrifugation. Granule-rich fractions obtained by this technique were extracted and analyzed by acrylamide gel electrophoresis, and proteolytic activity on the gels was demonstrated by staining with either N-acetyl-D,L-alanine alpha-naphthyl ester or naphthol AS-D acetate as substrate. In both species, all neutral proteases assayed were found to be localized exclusively in the azurophil granules. Specific activities were about 10-30 times higher in human than in rabbit preparations. In extracts of human azurophil granules up to 10 proteins exhibiting esterolytic activity could be demonstrated after electrophoretic separation. Three major and two or three minor components of these esterases were shown to possess elastase activity. Similar zymograms prepared with extracts from rabbit azurophil granules revealed only one major elastase band. The electrophoretic analysis further showed that the most strongly cationic proteins of both human and rabbit PMNs were also confined to the azurophil granules."}
{"id": "PMID:236355", "title": "Lymphocyte-induced angiogenesis: a quantitative and sensitive assay of the graft-vs.-host reaction.", "content": "A new and sensitive assay for the effect of intracutanous administration of immunocompentent lymphocytes into the skin of irradiated unimmunized mice is described. The assay, which we have termed lymphocyte-induced angiogenesis (LIA) involves enumeration of new vascular branches induced by the action of these competent cells. As is the case for the previously described normal lymphocyte transfer reaction, LIA is a manifestation of the graft-vs.-host reaction, as shown by experiments utilizing appropaiate genetic combinations. The reaction is dose-dependent, and within the dose range of 2 times 10 minus 5 -4 times 10-6 cells the mumber of vessels induced correlates with the mumber of immunocompetent cells injected. At these dose levels spleen, lumph node, and hydrocortisone-resistant  thymocytes are effective; bone marrow and thymus cells are not. Spleen cells from nude mice are incapable of inducing LIA, while mitomycin-C and irradiated lymphocytes can initiate but not maintain the reaction. The relationship between lymphocyte-induced angiogenesis has been discussed as have the implications of these findings to delayed hypersensitivity, inflammation, and vascular pathology.", "contents": "Lymphocyte-induced angiogenesis: a quantitative and sensitive assay of the graft-vs.-host reaction. A new and sensitive assay for the effect of intracutanous administration of immunocompentent lymphocytes into the skin of irradiated unimmunized mice is described. The assay, which we have termed lymphocyte-induced angiogenesis (LIA) involves enumeration of new vascular branches induced by the action of these competent cells. As is the case for the previously described normal lymphocyte transfer reaction, LIA is a manifestation of the graft-vs.-host reaction, as shown by experiments utilizing appropaiate genetic combinations. The reaction is dose-dependent, and within the dose range of 2 times 10 minus 5 -4 times 10-6 cells the mumber of vessels induced correlates with the mumber of immunocompetent cells injected. At these dose levels spleen, lumph node, and hydrocortisone-resistant  thymocytes are effective; bone marrow and thymus cells are not. Spleen cells from nude mice are incapable of inducing LIA, while mitomycin-C and irradiated lymphocytes can initiate but not maintain the reaction. The relationship between lymphocyte-induced angiogenesis has been discussed as have the implications of these findings to delayed hypersensitivity, inflammation, and vascular pathology."}
{"id": "PMID:236356", "title": "Cell membrane-binding properties of group A streptococcal lipoteichoic acid.", "content": "Lipoteichoic acid (LTA) was extracted from group A streptococci, previously treated with hot HCl, by the phenol method. The extracted LTA was loaded on an isoelectric (IE) focusing column and two fractions were collected; one at pH 4.65 and the other at pH 2.95. Chemical analysis demonstrated that the unfractionated LTA contained alanine and glycerolphosphate at molar ratio of 1:10, and ester-linked lipids, but no detectable sugars or amino-sugars. The two IE fractions contained lipids but lacked alanine. The LTA and its IE fractions spontaneously adsorbed to human erythrocytes (sensitization) causing them to agglutinate in the presence of rabbit anti-LTA. The RBC-sensitizing and antigenic activities of IE fractions were equal to, or greater (for IE fraction at pH 4.65) than the unfractionated LTA, indicating that alanine is not involved in the sensitizing activity of LTA. Mild ammonia-hydrolysis abolished the RBC-sensitizing activity of LTA and its IE fractions. Chloroform-methanol-soluble material of the ammonia-hydrolysate lacked antigenic activity but blocked sensitization of erythrocytes by LTA. The water-soluble material of the hydrolyzed LTA retained antigenic activity, was not able to block sensitization by LTA, and its sensitizing activity was restored after esterification with fatty acids. These experiments indicate that ester-linked fatty acids (palmitic acid being the major one) are involved in the spontaneous adsorption of LTA to erythrocytes. The LTA, its lipid moiety, and anti-LTA blocked adherence of group A streptococci to human epithelial cells, suggesting that small amounts of LTA may reside on the streptococcal surface to mediate attachment and colonization of these organisms on mucosal surfaces in vivo.", "contents": "Cell membrane-binding properties of group A streptococcal lipoteichoic acid. Lipoteichoic acid (LTA) was extracted from group A streptococci, previously treated with hot HCl, by the phenol method. The extracted LTA was loaded on an isoelectric (IE) focusing column and two fractions were collected; one at pH 4.65 and the other at pH 2.95. Chemical analysis demonstrated that the unfractionated LTA contained alanine and glycerolphosphate at molar ratio of 1:10, and ester-linked lipids, but no detectable sugars or amino-sugars. The two IE fractions contained lipids but lacked alanine. The LTA and its IE fractions spontaneously adsorbed to human erythrocytes (sensitization) causing them to agglutinate in the presence of rabbit anti-LTA. The RBC-sensitizing and antigenic activities of IE fractions were equal to, or greater (for IE fraction at pH 4.65) than the unfractionated LTA, indicating that alanine is not involved in the sensitizing activity of LTA. Mild ammonia-hydrolysis abolished the RBC-sensitizing activity of LTA and its IE fractions. Chloroform-methanol-soluble material of the ammonia-hydrolysate lacked antigenic activity but blocked sensitization of erythrocytes by LTA. The water-soluble material of the hydrolyzed LTA retained antigenic activity, was not able to block sensitization by LTA, and its sensitizing activity was restored after esterification with fatty acids. These experiments indicate that ester-linked fatty acids (palmitic acid being the major one) are involved in the spontaneous adsorption of LTA to erythrocytes. The LTA, its lipid moiety, and anti-LTA blocked adherence of group A streptococci to human epithelial cells, suggesting that small amounts of LTA may reside on the streptococcal surface to mediate attachment and colonization of these organisms on mucosal surfaces in vivo."}
{"id": "PMID:236357", "title": "The opsonic fragment of the third component of human complement (C3).", "content": "Human peripheral blood phagocytes ingest Escherichia coli 026:B6 lipopolysaccharide (LPS)-coated paraffin oil droplets containing Oil red O only if fresh serum deposits C3 on the surfaces of the particles (opsonizes them), by reactions involving the properdin system. The rate of binding of purified [125-I]C3 in serum to LPS-coated particles correlated precisely with the rate of acquisition of ingestibility assayed spectrophotometrically. Once opsonized, LPS-coated particles remained fully ingestible and retained fixed [125-I]C3 radioactivity even after exposure to extremes of temperature, pH, ionic strength, phospholipases, urea or guanidine, some nonionic and ionic detergents, and organic solvents. Trypsin, human conglutinogen-activating factor, another heat-stable activity found in human serum, and sodium dodecyl sulfate removed radioactivity and diminished ingestibility of the opsonized particles. Alkylation, reduction plus alkylation and F(ab')2 from anti-C3 blocked ingestibility but did not alter particle-bound radioactivitymelectrophoretic and tryptic peptide autoradiographic analysis of dodecyl sulfate eluates of opsonized particles, cleansed of many contaminating proteins by boiling with 2 M NaCl (yet still opsonized), revealed that the polypeptide with C3-derived radioactivity had a mol wt of approximately 140,000 and was composed of 70,000 mol wt subunits linked by disulfide bonds. Immunochemical analysis and comparison of the peptide structure of the eluate with that of C3 indicated that the opsonic fragment is not the fragment defined as C3b but a smaller derivative of C3.", "contents": "The opsonic fragment of the third component of human complement (C3). Human peripheral blood phagocytes ingest Escherichia coli 026:B6 lipopolysaccharide (LPS)-coated paraffin oil droplets containing Oil red O only if fresh serum deposits C3 on the surfaces of the particles (opsonizes them), by reactions involving the properdin system. The rate of binding of purified [125-I]C3 in serum to LPS-coated particles correlated precisely with the rate of acquisition of ingestibility assayed spectrophotometrically. Once opsonized, LPS-coated particles remained fully ingestible and retained fixed [125-I]C3 radioactivity even after exposure to extremes of temperature, pH, ionic strength, phospholipases, urea or guanidine, some nonionic and ionic detergents, and organic solvents. Trypsin, human conglutinogen-activating factor, another heat-stable activity found in human serum, and sodium dodecyl sulfate removed radioactivity and diminished ingestibility of the opsonized particles. Alkylation, reduction plus alkylation and F(ab')2 from anti-C3 blocked ingestibility but did not alter particle-bound radioactivitymelectrophoretic and tryptic peptide autoradiographic analysis of dodecyl sulfate eluates of opsonized particles, cleansed of many contaminating proteins by boiling with 2 M NaCl (yet still opsonized), revealed that the polypeptide with C3-derived radioactivity had a mol wt of approximately 140,000 and was composed of 70,000 mol wt subunits linked by disulfide bonds. Immunochemical analysis and comparison of the peptide structure of the eluate with that of C3 indicated that the opsonic fragment is not the fragment defined as C3b but a smaller derivative of C3."}
{"id": "PMID:236360", "title": "Primex trainees under stress.", "content": "In summary, it seems clear from the data presented in this report that nurses engaged in becoming a family nurse practitioner in the program studied undergo a considerable amount of social, physical, and psychological discomfort.  However, the data on the first class trained does suggest that the psychological and to a lesser extent the physical stress students experience during formal training subsides during the preceptorship.  Nevertheless, it is out contention that certain stressful periods in training cannot be avoided because of the nature and intensity of the course content as well as the role change necessary for becoming a responsible, dicisive practitioner.  Yet, experience with training two classes does suggest that although high stress probably cannot be avoided, at least the length of intense periods can be shortened.  In order to accomplish this, it is necessary to have a curriculum which is well-organized, clear in its purpose, and one which provides the opportunity for tension-release, discussion and development of role, and emotional support.  Finally, with regard to the perisitence of social stress both during and after training, there appears to be a need to provide continued support to students during their preceptorship in order to assure that role change and development continues.  In this regard, periodic continuing education sessions for students seem crucial as do discussions of role with both students and preceptors.  As the family nurse practitioner role evolves, it becomes increasingly clear that at times these new health professionals are neither doctors or nurses and at other times they are both.  However, nurse practitioners cannot meaningfully sustain their new and somewhat ambiguous role without the mutual cooperation and support of both the medical and nursing establishments in which they practice.", "contents": "Primex trainees under stress. In summary, it seems clear from the data presented in this report that nurses engaged in becoming a family nurse practitioner in the program studied undergo a considerable amount of social, physical, and psychological discomfort.  However, the data on the first class trained does suggest that the psychological and to a lesser extent the physical stress students experience during formal training subsides during the preceptorship.  Nevertheless, it is out contention that certain stressful periods in training cannot be avoided because of the nature and intensity of the course content as well as the role change necessary for becoming a responsible, dicisive practitioner.  Yet, experience with training two classes does suggest that although high stress probably cannot be avoided, at least the length of intense periods can be shortened.  In order to accomplish this, it is necessary to have a curriculum which is well-organized, clear in its purpose, and one which provides the opportunity for tension-release, discussion and development of role, and emotional support.  Finally, with regard to the perisitence of social stress both during and after training, there appears to be a need to provide continued support to students during their preceptorship in order to assure that role change and development continues.  In this regard, periodic continuing education sessions for students seem crucial as do discussions of role with both students and preceptors.  As the family nurse practitioner role evolves, it becomes increasingly clear that at times these new health professionals are neither doctors or nurses and at other times they are both.  However, nurse practitioners cannot meaningfully sustain their new and somewhat ambiguous role without the mutual cooperation and support of both the medical and nursing establishments in which they practice."}
{"id": "PMID:236361", "title": "Teaching nursing management by programmed instruction.", "content": "Student and faculty dissatisfaction with lectures prompted several revisions of teaching methods for nursing management.  Revisions centered around a programmed text for business plus various methods of application to nursing.  One part of management (control) was also programmed in nursing terms.  Data collected revealed that students who used the programmed business text and participated in small group discussions achieved significantly higher scores than either students who attended lectures or used the programmed business text in conjunction with a tutorial system.  Data also demonstrated that students who used the unit programmed specifically for nursing management achieved significantly higher scores than students who used the programmed text for business management.  This data suggest students level of achievement is increased when the transfer step from business to nursing is eliminated.  For this reason, two faculty members completed the writing of a programmed text for nursing management.  This text has been tested over the past two years and will be published in the near future.  We were unable to collect objective data regarding the actual application of management principles to nursing practice.  Subjectively, we felt the students had a stronger framework of principles unique to nursing management and were able to transfer this knowledge to leading a team with greater ease than previously.  Without student dissatisfaction originally, and student acceptance and participation throughout the changes, this study would not have evolved.  It was student encouragement which prompted the program specific to nursing.", "contents": "Teaching nursing management by programmed instruction. Student and faculty dissatisfaction with lectures prompted several revisions of teaching methods for nursing management.  Revisions centered around a programmed text for business plus various methods of application to nursing.  One part of management (control) was also programmed in nursing terms.  Data collected revealed that students who used the programmed business text and participated in small group discussions achieved significantly higher scores than either students who attended lectures or used the programmed business text in conjunction with a tutorial system.  Data also demonstrated that students who used the unit programmed specifically for nursing management achieved significantly higher scores than students who used the programmed text for business management.  This data suggest students level of achievement is increased when the transfer step from business to nursing is eliminated.  For this reason, two faculty members completed the writing of a programmed text for nursing management.  This text has been tested over the past two years and will be published in the near future.  We were unable to collect objective data regarding the actual application of management principles to nursing practice.  Subjectively, we felt the students had a stronger framework of principles unique to nursing management and were able to transfer this knowledge to leading a team with greater ease than previously.  Without student dissatisfaction originally, and student acceptance and participation throughout the changes, this study would not have evolved.  It was student encouragement which prompted the program specific to nursing."}
{"id": "PMID:236365", "title": "Distal renal tubular acidosis in infancy: a bicarbonate wasting state.", "content": "Three unrelated infants with apparently distal RTA were investigated. Growth retardation, polyuria, nephrocalcinosis, inappropriately high urinary pH, and marked dependence of bicarbonate excretion on urinary flow were characteristic of the distal or classic form of RTA, but the urinary loss of bicarbonate at normal serum values exceeded that usually found in children or adults with this disorder. Renal tubular function was studied during hypotonic saline diuresis in the three patients and in seven healthy control infants of similar age. Fractional delivery of sodium to the distal nephron was significantly higher in the patients than in control subjects. Sodium transport at the diluting segment was not impaired. The results support the assumption that the bicarbonate wasting was the consequence of an increased delivery of this substance to an already impaired distal nephron and thus further inhibited the distal mechanisms of net acid excretion.", "contents": "Distal renal tubular acidosis in infancy: a bicarbonate wasting state. Three unrelated infants with apparently distal RTA were investigated. Growth retardation, polyuria, nephrocalcinosis, inappropriately high urinary pH, and marked dependence of bicarbonate excretion on urinary flow were characteristic of the distal or classic form of RTA, but the urinary loss of bicarbonate at normal serum values exceeded that usually found in children or adults with this disorder. Renal tubular function was studied during hypotonic saline diuresis in the three patients and in seven healthy control infants of similar age. Fractional delivery of sodium to the distal nephron was significantly higher in the patients than in control subjects. Sodium transport at the diluting segment was not impaired. The results support the assumption that the bicarbonate wasting was the consequence of an increased delivery of this substance to an already impaired distal nephron and thus further inhibited the distal mechanisms of net acid excretion."}
{"id": "PMID:236368", "title": "Coronary aneurysms in infants and young children with acute febrile mucocutaneous lymph node syndrome.", "content": "In 1967, Kawasaki, in Japan, first described a new syndrome affecting infants and young children-an acute, febrile illness with mucocutaneous involvement associated with swelling of cervical lymph nodes. The prognosis is usually good but recently it has become evident that 1-2 percent of the patients die suddenly from acute heart failure. Infantile polyarteritis (nodosa-like arteritis) accompained by coronary aneurysm and thrombosis has been noted in postmortem examinations. Twenty patients surviving the illness were examined by coronary angiography; 12 of the 20 had abnormal coronary angiograms; seven patients had coronary aneurysms. Complete regression of the coronary aneurysms was proved in two patients at subsequent angiography. One patient developed mitral regurgitation as a result of papillary muscle dysfunction. One had a coronary aneurysm without symptoms two years after the onset of illness.", "contents": "Coronary aneurysms in infants and young children with acute febrile mucocutaneous lymph node syndrome. In 1967, Kawasaki, in Japan, first described a new syndrome affecting infants and young children-an acute, febrile illness with mucocutaneous involvement associated with swelling of cervical lymph nodes. The prognosis is usually good but recently it has become evident that 1-2 percent of the patients die suddenly from acute heart failure. Infantile polyarteritis (nodosa-like arteritis) accompained by coronary aneurysm and thrombosis has been noted in postmortem examinations. Twenty patients surviving the illness were examined by coronary angiography; 12 of the 20 had abnormal coronary angiograms; seven patients had coronary aneurysms. Complete regression of the coronary aneurysms was proved in two patients at subsequent angiography. One patient developed mitral regurgitation as a result of papillary muscle dysfunction. One had a coronary aneurysm without symptoms two years after the onset of illness."}
{"id": "PMID:236371", "title": "Bisulfite-ion-catalyzed degradation of fluorouracil.", "content": "5-Fluorouracil (I) reversibly adds bisulfite ion across its greater than C5 equals C6 smaller than bond to form 5-fluoro-5,6-dihydrouracil-6-sulfonate (II). The pH-independent equilibrium constant for this reaction was calculated to be 560 M-1 at ionic strength 1.00 M at 25 degrees. Compound II was observed to be unstable in alkaline solution and reacted to yield uracil-6-sulfonic acid, fluoride ion, and alpha-fluoro-beta-ureidopropionic acid-beta-sulfonate (III), along with I (via a loss of HSO3 minus). In strongly alkaline conditions, i.e., 1 M NaOH, III was observed to undergo a subsequent reaction to produce a compound believed to be alpha-fluoro-beta-ureidoacrylic acid (V) or fluoromalonaldehydic acid (VII). These irreversible degradation reactions of II lead to a complete degradation of I in sodium bisulfite solutions. The similarity of this bisulfite-ion-catalyzed degradation of I to its hydrolytic degradation is discussed.", "contents": "Bisulfite-ion-catalyzed degradation of fluorouracil. 5-Fluorouracil (I) reversibly adds bisulfite ion across its greater than C5 equals C6 smaller than bond to form 5-fluoro-5,6-dihydrouracil-6-sulfonate (II). The pH-independent equilibrium constant for this reaction was calculated to be 560 M-1 at ionic strength 1.00 M at 25 degrees. Compound II was observed to be unstable in alkaline solution and reacted to yield uracil-6-sulfonic acid, fluoride ion, and alpha-fluoro-beta-ureidopropionic acid-beta-sulfonate (III), along with I (via a loss of HSO3 minus). In strongly alkaline conditions, i.e., 1 M NaOH, III was observed to undergo a subsequent reaction to produce a compound believed to be alpha-fluoro-beta-ureidoacrylic acid (V) or fluoromalonaldehydic acid (VII). These irreversible degradation reactions of II lead to a complete degradation of I in sodium bisulfite solutions. The similarity of this bisulfite-ion-catalyzed degradation of I to its hydrolytic degradation is discussed."}
{"id": "PMID:236373", "title": "Practical kinetics I: Quantitation of barbiturate stability by TLC.", "content": "The purpose of this work was the application of established techniques to the quantitation of stability investigations of liquid formulations as well as in solution kinetic studies. The process consists of streaking aliquots of reaction solution on TLC plates, development, elution, and analysis of the substances in the eluate. Several barbiturates were investigated regarding their decomposition at elevated temperatures. Reasonable correlation is noted between obtained rate constants and literature data. This technique represents a utilitarian approach to stability screening of compounds in solution, aqueous or otherwise, where chromatographic separation and analytical methodology for the pure compound are available.", "contents": "Practical kinetics I: Quantitation of barbiturate stability by TLC. The purpose of this work was the application of established techniques to the quantitation of stability investigations of liquid formulations as well as in solution kinetic studies. The process consists of streaking aliquots of reaction solution on TLC plates, development, elution, and analysis of the substances in the eluate. Several barbiturates were investigated regarding their decomposition at elevated temperatures. Reasonable correlation is noted between obtained rate constants and literature data. This technique represents a utilitarian approach to stability screening of compounds in solution, aqueous or otherwise, where chromatographic separation and analytical methodology for the pure compound are available."}
{"id": "PMID:236374", "title": "Practical kinetics II: quantitation of procaine stability by TLC.", "content": "This work illustrates further application of TLC as a tool in kinetic investigations of organic molecules. The procedure consists of: (a) streaking or spotting a known volume of reaction solution on thin-layer plates, (b) developing the plates, (c) eluting the compound under study from the adsorbent, and (d) assaying the material in solution. Procaine was examined regarding its hydrolysis at above ambient temperatures. The reaction was monitored spectrally and by the TLC technique. Velocity constants derived by the two methods were similar in value. Rate constants obtained from procaine samples eluted from silica gel plates following development were in good agreement with those previously reported in the literature.", "contents": "Practical kinetics II: quantitation of procaine stability by TLC. This work illustrates further application of TLC as a tool in kinetic investigations of organic molecules. The procedure consists of: (a) streaking or spotting a known volume of reaction solution on thin-layer plates, (b) developing the plates, (c) eluting the compound under study from the adsorbent, and (d) assaying the material in solution. Procaine was examined regarding its hydrolysis at above ambient temperatures. The reaction was monitored spectrally and by the TLC technique. Velocity constants derived by the two methods were similar in value. Rate constants obtained from procaine samples eluted from silica gel plates following development were in good agreement with those previously reported in the literature."}
{"id": "PMID:236375", "title": "Practical kinetics III: benzodiazepine hydrolysis.", "content": "The velocity constants for chlordiazepoxide hydrolysis were measured by independent techniques. A quantitative TLC kinetic procedure is compared with an extractive method. The data derived from both processes are in approximate agreement, further exemplifying the feasibility of TLC for rapid stability evaluation of liquid formulations as well as solution kinetic studies. In the extractive procedure, benzodiazepine-substrate was separated from the lactam product by methylene chloride extraction of acidic aqueous solution. The TLC procedure consisted of separation on silica gel plates followed by elution and subsequent analysis. The log kappa-pH relationship for the hydrolysis representing water addition coupled with expulsion of methylamine is presented. This function is characterized by water and hydroxide-ion attack on monoprotic species along with specific hydrogen-ion catalysis at higher hydronium-ion concentrations, and the rate law for the decomposition of chlordiazepoxide is given. Trhrough several half-times (pH 0.15-11.5, 79.5 degrees), this hydrolytic reaction generating lactam predominated; however, more benzophenone was formed as the pH decreased. Velocity constants were invariant over a 200-fold concentration range. The subsequent acid-facilitated cleavage of lactam to benzophenone was not further investigated. Both general acid catalysis and general base catalysis were evidenced, with borate, acetate, formate, and phosphate buffers accelerating the conversion of chlordiazepoxide to lactam. At pH values below neutrality, nonlinear dependency of the rate constant on buffer concentration was observed. This finding may be explained by a change in the rate-determining step as buffer concentration varied.", "contents": "Practical kinetics III: benzodiazepine hydrolysis. The velocity constants for chlordiazepoxide hydrolysis were measured by independent techniques. A quantitative TLC kinetic procedure is compared with an extractive method. The data derived from both processes are in approximate agreement, further exemplifying the feasibility of TLC for rapid stability evaluation of liquid formulations as well as solution kinetic studies. In the extractive procedure, benzodiazepine-substrate was separated from the lactam product by methylene chloride extraction of acidic aqueous solution. The TLC procedure consisted of separation on silica gel plates followed by elution and subsequent analysis. The log kappa-pH relationship for the hydrolysis representing water addition coupled with expulsion of methylamine is presented. This function is characterized by water and hydroxide-ion attack on monoprotic species along with specific hydrogen-ion catalysis at higher hydronium-ion concentrations, and the rate law for the decomposition of chlordiazepoxide is given. Trhrough several half-times (pH 0.15-11.5, 79.5 degrees), this hydrolytic reaction generating lactam predominated; however, more benzophenone was formed as the pH decreased. Velocity constants were invariant over a 200-fold concentration range. The subsequent acid-facilitated cleavage of lactam to benzophenone was not further investigated. Both general acid catalysis and general base catalysis were evidenced, with borate, acetate, formate, and phosphate buffers accelerating the conversion of chlordiazepoxide to lactam. At pH values below neutrality, nonlinear dependency of the rate constant on buffer concentration was observed. This finding may be explained by a change in the rate-determining step as buffer concentration varied."}
{"id": "PMID:236376", "title": "New color reaction for determination of bacitracin in ophthalmic ointments.", "content": "A colorimetric method was developed for the rapid analysis of bacitracin in ophthalmic ointments. The method involves the oxidation of alpha-aminocarboxylic acid with sodium hypobromite in an alkaline medium and condensation of the resulting aldehyde with phloroglucinol in concentrated hydrochloric acid to yield a pink color which gives an absorbance maximum at 505 nm. The relationship between absorbance and the quantity of bacitracin reacted obeyed Beer's law over the 15-100-mug/ml concentration range studied, and the produced color was stable for several hours. Furthermore, the method, which can be applied directly to the aqueous dissolution sample, gave results comparable to the official microbiological analytical procedure. The standard deviation is equal to plus or minus 1.81%.", "contents": "New color reaction for determination of bacitracin in ophthalmic ointments. A colorimetric method was developed for the rapid analysis of bacitracin in ophthalmic ointments. The method involves the oxidation of alpha-aminocarboxylic acid with sodium hypobromite in an alkaline medium and condensation of the resulting aldehyde with phloroglucinol in concentrated hydrochloric acid to yield a pink color which gives an absorbance maximum at 505 nm. The relationship between absorbance and the quantity of bacitracin reacted obeyed Beer's law over the 15-100-mug/ml concentration range studied, and the produced color was stable for several hours. Furthermore, the method, which can be applied directly to the aqueous dissolution sample, gave results comparable to the official microbiological analytical procedure. The standard deviation is equal to plus or minus 1.81%."}
{"id": "PMID:236377", "title": "Liquid chromatography of clindamycin 2-phosphate on triethylaminoethyl cellulose.", "content": "The separation of clindamycin 2-phosphate from clindamycin 3-phosphate, clindamycin 4-phosphate, clindamycin B 2-phosphate, and lincomycin 2-phosphate was achieved by liquid chromatography on triethylaminoethyl cellulose using a 254-nm monitor. The compounds have low molar absorptivities at 254 nm (smaller than 17), and UV detection is made possible by the high capacity support triethylaminoethyl cellulose. Linear peak height response versus concentration allows rapid quantitation of clindamycin 2-phosphate.", "contents": "Liquid chromatography of clindamycin 2-phosphate on triethylaminoethyl cellulose. The separation of clindamycin 2-phosphate from clindamycin 3-phosphate, clindamycin 4-phosphate, clindamycin B 2-phosphate, and lincomycin 2-phosphate was achieved by liquid chromatography on triethylaminoethyl cellulose using a 254-nm monitor. The compounds have low molar absorptivities at 254 nm (smaller than 17), and UV detection is made possible by the high capacity support triethylaminoethyl cellulose. Linear peak height response versus concentration allows rapid quantitation of clindamycin 2-phosphate."}
{"id": "PMID:236378", "title": "Conversion of agroclavine to setoclavine and isosetoclavine in cell-free extracts from Claviceps sp. SD 58 and in a thioglycolate-iron (II) system.", "content": "Agroclavine was converted to setoclavine and isosetoclavine in crude extracts from Claviceps sp. SD 58. The ratio of setoclavine to isosetoclavine was 0.95. The conversion with boiled crude extract was 68% of the conversion with unboiled extract. In a thioglycolate-iron (II) system at 40 degrees for 5 hr, 45.5% of agroclavine was converted to setoclavine and isosetoclavine. At 70 degrees for 4 hr in the thioglycolate-iron (II) system, 4% of 4-dimethylallyltryptophan was converted to clavicipitic acid.", "contents": "Conversion of agroclavine to setoclavine and isosetoclavine in cell-free extracts from Claviceps sp. SD 58 and in a thioglycolate-iron (II) system. Agroclavine was converted to setoclavine and isosetoclavine in crude extracts from Claviceps sp. SD 58. The ratio of setoclavine to isosetoclavine was 0.95. The conversion with boiled crude extract was 68% of the conversion with unboiled extract. In a thioglycolate-iron (II) system at 40 degrees for 5 hr, 45.5% of agroclavine was converted to setoclavine and isosetoclavine. At 70 degrees for 4 hr in the thioglycolate-iron (II) system, 4% of 4-dimethylallyltryptophan was converted to clavicipitic acid."}
{"id": "PMID:236379", "title": "Determination of stability constants of stannous fluoride complexes by potentiostatic titration.", "content": "The stability constants for stannous fluoride complexes were determined by potentiostatic titration. The method involves incremental additions of fluoride wherein each addition is followed by titration with stannous such that there is no change in the electromotive force developed between the fluoride ion and the reference electrodes. The values obtained were beta1 equals 4 times 10-3, b2 equals 1.1 times 10-7, and b3 equals 1 times 10-9. The results of this work suggest that the potentiostatic method wound be useful for determining stability constants in complexation systems involving an ion for which a specific on electrode is available.", "contents": "Determination of stability constants of stannous fluoride complexes by potentiostatic titration. The stability constants for stannous fluoride complexes were determined by potentiostatic titration. The method involves incremental additions of fluoride wherein each addition is followed by titration with stannous such that there is no change in the electromotive force developed between the fluoride ion and the reference electrodes. The values obtained were beta1 equals 4 times 10-3, b2 equals 1.1 times 10-7, and b3 equals 1 times 10-9. The results of this work suggest that the potentiostatic method wound be useful for determining stability constants in complexation systems involving an ion for which a specific on electrode is available."}
{"id": "PMID:236380", "title": "Indolizines II: search for potential oral hypoglycemic agents.", "content": "A few 1,2-bis(N-alkylaminomethyl)indolizines, simple indolizinecarboxylic acids, and several 6-alkoxyindolizine-2-carboxylic acids were synthesized and screened as possible oral hypoglycemic agents. The absence of any significant hypoglycemic activity excludes these compounds from the predicted structural lead provided by some hypoglycemic Vinca alkaloids, such as vincamine, vindoline, and vindolinine, having the indolizine ring as one structural component. But an extension of the rationale that indolizines are also the structural components of some carcinolytic Vinca alkaloids, such as vincristine and vinblastine, used in cancer chemotherapy provided encouraging results. One indolizine derivative showed significant antineoplastic activity in Ehrlich ascites carcinoma.", "contents": "Indolizines II: search for potential oral hypoglycemic agents. A few 1,2-bis(N-alkylaminomethyl)indolizines, simple indolizinecarboxylic acids, and several 6-alkoxyindolizine-2-carboxylic acids were synthesized and screened as possible oral hypoglycemic agents. The absence of any significant hypoglycemic activity excludes these compounds from the predicted structural lead provided by some hypoglycemic Vinca alkaloids, such as vincamine, vindoline, and vindolinine, having the indolizine ring as one structural component. But an extension of the rationale that indolizines are also the structural components of some carcinolytic Vinca alkaloids, such as vincristine and vinblastine, used in cancer chemotherapy provided encouraging results. One indolizine derivative showed significant antineoplastic activity in Ehrlich ascites carcinoma."}
{"id": "PMID:236381", "title": "Renal function in sheep during infusion of alkali metal ions into the renal artery.", "content": "1. The effect on renal function of 1 M solutions of LiCl, NaCl, KCl, RbCl and CsCl and 3 M-NaCl infused close-arterially to the kidney for 10 min at 0-7ml./min has been studied in nine experiments on four unilaterally nephrectomized sheep. The levels of flow, electrolyte concentration and electrolyte excretion in the urine were measured before, during and for 50 min after the infusions. 2. The infusion of 1-M-NaCl produced little change in urine flow and composition whereas 3 M-NaCl resulted in relatively small increases in urine flow and sodium excretion. 3. The infusion of lithium, potassium, rubidium and caesium resulted in marked increases in urine flow, urinary sodium concentration and excretion, urinary potassium excretion and osmolal clearance while the urinary potassium concentration decreased. 4. Changes in urine flow and urinary pH during the infusions of all the alkali ions except sodium were consistent with increased urinary bicarbonate excretion. 5. The osmolal clearance was increased by the infusion of lithium, potassium, rubidium and caesium, but equivalent increases in the rate of solutefree water reabsorption did not occur. 6. The infusion of caesium resulted in a depression of the glomerular filtration rate (G.F.R.) which was not observed when the other alkali ions were infused. 7. The effects of lithium, potassium and rubidium on urine flow and composition were rapid in onset and the residual effects on these ions, on cessation of infusion, were relatively short. The effects on caesium were slow in onset and prolonged in duration. 8. It was concluded that lithium, potassium, rubidium, and caesium altered urine flow and electrolyte excretion by acting upon common mechanisms which were predominantly intra-renal and located in the proximal segment of the nephron.", "contents": "Renal function in sheep during infusion of alkali metal ions into the renal artery. 1. The effect on renal function of 1 M solutions of LiCl, NaCl, KCl, RbCl and CsCl and 3 M-NaCl infused close-arterially to the kidney for 10 min at 0-7ml./min has been studied in nine experiments on four unilaterally nephrectomized sheep. The levels of flow, electrolyte concentration and electrolyte excretion in the urine were measured before, during and for 50 min after the infusions. 2. The infusion of 1-M-NaCl produced little change in urine flow and composition whereas 3 M-NaCl resulted in relatively small increases in urine flow and sodium excretion. 3. The infusion of lithium, potassium, rubidium and caesium resulted in marked increases in urine flow, urinary sodium concentration and excretion, urinary potassium excretion and osmolal clearance while the urinary potassium concentration decreased. 4. Changes in urine flow and urinary pH during the infusions of all the alkali ions except sodium were consistent with increased urinary bicarbonate excretion. 5. The osmolal clearance was increased by the infusion of lithium, potassium, rubidium and caesium, but equivalent increases in the rate of solutefree water reabsorption did not occur. 6. The infusion of caesium resulted in a depression of the glomerular filtration rate (G.F.R.) which was not observed when the other alkali ions were infused. 7. The effects of lithium, potassium and rubidium on urine flow and composition were rapid in onset and the residual effects on these ions, on cessation of infusion, were relatively short. The effects on caesium were slow in onset and prolonged in duration. 8. It was concluded that lithium, potassium, rubidium, and caesium altered urine flow and electrolyte excretion by acting upon common mechanisms which were predominantly intra-renal and located in the proximal segment of the nephron."}
{"id": "PMID:236383", "title": "[Takayasu's disease (aortic arch syndrome). Usual and unusual angiographic appearances. Report of 15 cases treated by arteriography (author's transl)].", "content": "The authors report 15 cases including 9 controlled by autopsy, and discuss the usual and unusual angiographic appearances in this disease. These cases strictly fulfilled the criteria necessary for diagnosis. The two angiographic forms seemed to correspond to different therapeutic indications. Takayasu's disease remains a disease of young women and the angiographic diagnosis can only be made during the obstructive phase.", "contents": "[Takayasu's disease (aortic arch syndrome). Usual and unusual angiographic appearances. Report of 15 cases treated by arteriography (author's transl)]. The authors report 15 cases including 9 controlled by autopsy, and discuss the usual and unusual angiographic appearances in this disease. These cases strictly fulfilled the criteria necessary for diagnosis. The two angiographic forms seemed to correspond to different therapeutic indications. Takayasu's disease remains a disease of young women and the angiographic diagnosis can only be made during the obstructive phase."}
{"id": "PMID:236384", "title": "[Aortic arch syndrome. Stenosis and obstruction of the sub-clavian artery in women (author's transl)].", "content": "Takayasu's disease evolves in two stages: The pre-obstructive state: frequently it gives rise to infectious diseases which often resemble rheumatic fever. Often there exist fever and joint pains. Laboratory examinations show the presence of an inflammatory process: increased ESR hypoalbuminuria and increased alpha-2 and gammaglobulins. Then one reaches the obstructive stage. Here the diagnosis of the disease is often suspected or confirmed. Often there are eye signs with the characteristic appearance of arteriovenous anastomoses in the fundus oculi. These signs were absent. The etiology is unknown. The authors propose the following definition: that this is a form of juvenile arteritis occurring, above all, in women and involving one or other of the main aortic trunks, but which may be diffuse. The disease is often inflammatory. The etiology is unknown.", "contents": "[Aortic arch syndrome. Stenosis and obstruction of the sub-clavian artery in women (author's transl)]. Takayasu's disease evolves in two stages: The pre-obstructive state: frequently it gives rise to infectious diseases which often resemble rheumatic fever. Often there exist fever and joint pains. Laboratory examinations show the presence of an inflammatory process: increased ESR hypoalbuminuria and increased alpha-2 and gammaglobulins. Then one reaches the obstructive stage. Here the diagnosis of the disease is often suspected or confirmed. Often there are eye signs with the characteristic appearance of arteriovenous anastomoses in the fundus oculi. These signs were absent. The etiology is unknown. The authors propose the following definition: that this is a form of juvenile arteritis occurring, above all, in women and involving one or other of the main aortic trunks, but which may be diffuse. The disease is often inflammatory. The etiology is unknown."}
{"id": "PMID:236385", "title": "Effect of long-term addiction to heroin on oral tissues.", "content": "The oral health status of 36 long-term heroin addicts was measured using DMF, OHIS, and PI. Comparisons were made utilizing data from the National Center for Health Statistics. Age, sex, race, education, income, and geographic location were compared. The former addicts exhibited a significant increase in DMF, with significantly higher missing and decayed teeth, and fewer filled teeth. The periodontal condition of the former addict also showed health status. It would appear that long-term heroin addiction either contributes directly to lowered oral health status, or more likely, causes individuals to lead a life style which has ramifications to their oral health.", "contents": "Effect of long-term addiction to heroin on oral tissues. The oral health status of 36 long-term heroin addicts was measured using DMF, OHIS, and PI. Comparisons were made utilizing data from the National Center for Health Statistics. Age, sex, race, education, income, and geographic location were compared. The former addicts exhibited a significant increase in DMF, with significantly higher missing and decayed teeth, and fewer filled teeth. The periodontal condition of the former addict also showed health status. It would appear that long-term heroin addiction either contributes directly to lowered oral health status, or more likely, causes individuals to lead a life style which has ramifications to their oral health."}
{"id": "PMID:236386", "title": "Causes of accidental injuries to the teeth and jaws.", "content": "Almost one half of all the dental accidents recorded during this study occurred when the victim was moving and struck a stationary object. Falls and vehicles were about equally responsible for half of the accidents. Accident proneness seemed to be affected by age and sex with the teenage group reporting the most dental accidents (35.76%) and males reported dental accidents three times as often as females. Of orthodontic patients, 16.43 percent had a history of dental accidents in contrast to about five percent of the general population. From the limited data available, approximately three fourths of the persons reporting said no seat belts were available in their automobiles. The remaining one fourth had belts but they were not being used at the time of the dental injury. Right-handed victims tended to be injured on the right side of the mouth and jaw and left-handed victims exhibited more injuries on the left side. As was anticipated, a high percentage (23 percent) of the residents of a hospital for the mentally retarded exhibited dental injuries.", "contents": "Causes of accidental injuries to the teeth and jaws. Almost one half of all the dental accidents recorded during this study occurred when the victim was moving and struck a stationary object. Falls and vehicles were about equally responsible for half of the accidents. Accident proneness seemed to be affected by age and sex with the teenage group reporting the most dental accidents (35.76%) and males reported dental accidents three times as often as females. Of orthodontic patients, 16.43 percent had a history of dental accidents in contrast to about five percent of the general population. From the limited data available, approximately three fourths of the persons reporting said no seat belts were available in their automobiles. The remaining one fourth had belts but they were not being used at the time of the dental injury. Right-handed victims tended to be injured on the right side of the mouth and jaw and left-handed victims exhibited more injuries on the left side. As was anticipated, a high percentage (23 percent) of the residents of a hospital for the mentally retarded exhibited dental injuries."}
{"id": "PMID:236387", "title": "The removal of the seminal vesicles from the boar and the effects on the semen characteristics.", "content": "A technique is described for the removal of the seminal vesicles from the boar. The operation was carried out on twelve animals and six of the animals were subsequently trained for semen collection. The seminal plasma from the boars after surgery compared with normal litter mates had a more watery consistency and did not form the characteristic gelduring ejaculation. The sperm concentration was 49% lower while the total reduction of sperm number ejaculate was 78% in the experimental animals, but the ratio of living to dead spermatozoa remained unchanged. The concentrations of citrate and protein were significantly depressed in the seminal plasma of the animals after surgery and the pH increased; the osmolarity remained unchanged. In semination of gilts with the semen from experimental boars revealed no significant loss of fertility compared with the normal controls. Animals slaughtered up to 17 months after surgery showed no regeneration of the seminal vesicles.", "contents": "The removal of the seminal vesicles from the boar and the effects on the semen characteristics. A technique is described for the removal of the seminal vesicles from the boar. The operation was carried out on twelve animals and six of the animals were subsequently trained for semen collection. The seminal plasma from the boars after surgery compared with normal litter mates had a more watery consistency and did not form the characteristic gelduring ejaculation. The sperm concentration was 49% lower while the total reduction of sperm number ejaculate was 78% in the experimental animals, but the ratio of living to dead spermatozoa remained unchanged. The concentrations of citrate and protein were significantly depressed in the seminal plasma of the animals after surgery and the pH increased; the osmolarity remained unchanged. In semination of gilts with the semen from experimental boars revealed no significant loss of fertility compared with the normal controls. Animals slaughtered up to 17 months after surgery showed no regeneration of the seminal vesicles."}
{"id": "PMID:236389", "title": "A solid medium for culture and identification of human T-mycoplasmas.", "content": "A solid urea-containing medium buffered to pH 6.5 with a suitable mixture of KH2PO4 and Na2HPO4 produced enlarged T-mycoplasma colonies containing a white precipitate. This was absent from M. hominis colonies. The medium can be used for the isolation and identification of T-mycoplasmas.", "contents": "A solid medium for culture and identification of human T-mycoplasmas. A solid urea-containing medium buffered to pH 6.5 with a suitable mixture of KH2PO4 and Na2HPO4 produced enlarged T-mycoplasma colonies containing a white precipitate. This was absent from M. hominis colonies. The medium can be used for the isolation and identification of T-mycoplasmas."}
{"id": "PMID:236390", "title": "Impedance monitoring of bacterial activity.", "content": "Bacterial activity and growth were monitored by following the changes of electrical impedance of cultures in liquid media. The signal is expressed automatically as a curve similar to grwoth curves produced by other methods. The technique offers a new, rapid and sensitive means of detecting active micro-organisms and is potentially the basis of rapid automated systems in this field. The impedance changes indicate that the micro-organisms metabolise substrates of low conductivity into products of high conductivity and that the changes are due to the activity of the micro-organisms rather than increase in their numbers. The activity of strains of Escherichia coli, Klebsiella aerogenes, Pseudo-monas aeruginosa, Staphyloccus aureus, and Streptococcus faecalis was detected within 2 h with inocula of 10-3 minus 10-5 organisms per ml. Different reactions of bacteria in various media suggest that the method may be applied to the rapid identification of micro-organisms. The inhibitory effect of antibiotics on bacteria was demonstrated within 2 h, indicating that the method may be useful for the rapid determination of bacterial sensitivity to antibiotics and the rapid assay of antibiotics in serum. Correlation of response time to initial inoculum allows estimatin of numbers of viable organisms. The sensitivity of the method allowed detection of activity due to Myoplasma argininii within 3 h; this suggests that the method might be applicable to the rapid detection of other slowly growing organisms, such as mycobacteria.", "contents": "Impedance monitoring of bacterial activity. Bacterial activity and growth were monitored by following the changes of electrical impedance of cultures in liquid media. The signal is expressed automatically as a curve similar to grwoth curves produced by other methods. The technique offers a new, rapid and sensitive means of detecting active micro-organisms and is potentially the basis of rapid automated systems in this field. The impedance changes indicate that the micro-organisms metabolise substrates of low conductivity into products of high conductivity and that the changes are due to the activity of the micro-organisms rather than increase in their numbers. The activity of strains of Escherichia coli, Klebsiella aerogenes, Pseudo-monas aeruginosa, Staphyloccus aureus, and Streptococcus faecalis was detected within 2 h with inocula of 10-3 minus 10-5 organisms per ml. Different reactions of bacteria in various media suggest that the method may be applied to the rapid identification of micro-organisms. The inhibitory effect of antibiotics on bacteria was demonstrated within 2 h, indicating that the method may be useful for the rapid determination of bacterial sensitivity to antibiotics and the rapid assay of antibiotics in serum. Correlation of response time to initial inoculum allows estimatin of numbers of viable organisms. The sensitivity of the method allowed detection of activity due to Myoplasma argininii within 3 h; this suggests that the method might be applicable to the rapid detection of other slowly growing organisms, such as mycobacteria."}
{"id": "PMID:236393", "title": "Human placental aryl hydrocarbon hydroxylase: studies with fluorescence histochemistry.", "content": "Tissue sections from human placentas taken at term were studied after time-sequential incubations with benzo[a]pyrene and appropriate cofactors for mixed-function oxidation. Fluorescence microscopy revealed that the enzymic reaction appeared to be most active in the syncytial trophoblast, though the fluorescence of hydroxylated metabolites also could be observed in other placental cell types. A comparison of sections from placentas with very low versus very high aryl hydrocarbon hydroxylase activities provided evidence that induction of the human placental enzyme system with pol7cyclic aromatic hydrocarbons also appeared to occur primarily in the syncytium. When considered in conjunction with previous studies on human placental aryl hydrocarbon hydroxylase, the results tended to indicate that fetal elements of the human placenta contain the necessary electron-transport components for catalysis of mixed-function oxidations of chemical carcinogens and other foreign compounds and that this hydroxtlase system is readily inducible in the same fetal cells by components present in cigarette smoke.", "contents": "Human placental aryl hydrocarbon hydroxylase: studies with fluorescence histochemistry. Tissue sections from human placentas taken at term were studied after time-sequential incubations with benzo[a]pyrene and appropriate cofactors for mixed-function oxidation. Fluorescence microscopy revealed that the enzymic reaction appeared to be most active in the syncytial trophoblast, though the fluorescence of hydroxylated metabolites also could be observed in other placental cell types. A comparison of sections from placentas with very low versus very high aryl hydrocarbon hydroxylase activities provided evidence that induction of the human placental enzyme system with pol7cyclic aromatic hydrocarbons also appeared to occur primarily in the syncytium. When considered in conjunction with previous studies on human placental aryl hydrocarbon hydroxylase, the results tended to indicate that fetal elements of the human placenta contain the necessary electron-transport components for catalysis of mixed-function oxidations of chemical carcinogens and other foreign compounds and that this hydroxtlase system is readily inducible in the same fetal cells by components present in cigarette smoke."}
{"id": "PMID:236394", "title": "Disappearance of nitrite from the rat stomach: contribution of emptying and other factors.", "content": "To help understand how intragastric nitrosation forms N-nitroso compounds, nitriet disappearance from the rat stomach was measured after food containing nitrite was given. In preliminary experiments, nitrite disappearance from buffered aqueous solutions became more rapid as the pH was lowered from 5 to 1 and, at a given pH, was more rapid in a slurry of commercial rat food. The disappearance of nitrite from buffer was little affected by the addition of pepsin, mucin, albumin, or rat gastric contents. When starved rats were given 5 g food with 1.82 mg nANO3/g, nitrate was not reduced to nitrite in the stomach. Five g food containing 154 mug NaNO2/g was administered similarly, and the total stomach (T) and glandular and nonglandular parts (G and NG) were analyzed after 1.5 hours. Weight and nitrite concentration of the stomach contents dropped linearly and the amount of nitrite dropped exponentially (with a half-life of 1.4 hr). Mean nitrite concentration in G was less than half that in NG. From similar experiments with phenol red, emptying accounted for 60% of nitrite loss from T. In G, nitrite concentration was reduced about 3 times due to dilution and 3 times due to other causes. Conditions in G, e.g., nitrite concentration, pH, and empyting time, were discussed in relation to carcinogenesis experiments with nitrite plus amines and amides.", "contents": "Disappearance of nitrite from the rat stomach: contribution of emptying and other factors. To help understand how intragastric nitrosation forms N-nitroso compounds, nitriet disappearance from the rat stomach was measured after food containing nitrite was given. In preliminary experiments, nitrite disappearance from buffered aqueous solutions became more rapid as the pH was lowered from 5 to 1 and, at a given pH, was more rapid in a slurry of commercial rat food. The disappearance of nitrite from buffer was little affected by the addition of pepsin, mucin, albumin, or rat gastric contents. When starved rats were given 5 g food with 1.82 mg nANO3/g, nitrate was not reduced to nitrite in the stomach. Five g food containing 154 mug NaNO2/g was administered similarly, and the total stomach (T) and glandular and nonglandular parts (G and NG) were analyzed after 1.5 hours. Weight and nitrite concentration of the stomach contents dropped linearly and the amount of nitrite dropped exponentially (with a half-life of 1.4 hr). Mean nitrite concentration in G was less than half that in NG. From similar experiments with phenol red, emptying accounted for 60% of nitrite loss from T. In G, nitrite concentration was reduced about 3 times due to dilution and 3 times due to other causes. Conditions in G, e.g., nitrite concentration, pH, and empyting time, were discussed in relation to carcinogenesis experiments with nitrite plus amines and amides."}
{"id": "PMID:236395", "title": "Transplantation behavior of allotransplantable tumor lines derived from immunologically modified hosts.", "content": "The strain-specific BALB/c tumor C4092 was conditioned to grow in H-2 incompatible DBA/1 mice by prior maintenance in vitro as an organ culture explant. It then was serially transplantable in DBA/1 mice and regained its specificity with one passage in BALB/c mice. Changes in transplantation behavior were similar in  vivo if the recipients were conditioned by neonatal thymectomy, immunologic enhancement, rabbit antimous serum treatment, or immunization with mitomycin C-inactivated C4092 tumor cells. In vivo- and in vitro-modified tumors differed in degree of transplantability and in the stability of immunogenic changes. However, because of conspicuous similarities in the behavior of these lines, it was concluded that ADAPTations of both host and graft ultimately contribute to graft survival.", "contents": "Transplantation behavior of allotransplantable tumor lines derived from immunologically modified hosts. The strain-specific BALB/c tumor C4092 was conditioned to grow in H-2 incompatible DBA/1 mice by prior maintenance in vitro as an organ culture explant. It then was serially transplantable in DBA/1 mice and regained its specificity with one passage in BALB/c mice. Changes in transplantation behavior were similar in  vivo if the recipients were conditioned by neonatal thymectomy, immunologic enhancement, rabbit antimous serum treatment, or immunization with mitomycin C-inactivated C4092 tumor cells. In vivo- and in vitro-modified tumors differed in degree of transplantability and in the stability of immunogenic changes. However, because of conspicuous similarities in the behavior of these lines, it was concluded that ADAPTations of both host and graft ultimately contribute to graft survival."}
{"id": "PMID:236396", "title": "Proteases during the growth of Ehrlich ascites tumor. II. The kallikrein-kinin system.", "content": "Ascitic fluid and ascites tumor cells from Swiss mice bearing Ehrlich ascites tumor were assayed for components of the kallikrein-kinin system at various times during tumor growth. Changes in component levels were correlated with those in the plasma. Ascitic fluid contained an acetone-activated prekallikrein that increased in concentration during tumor growth and reached peak levels during the 7th-10th day post transplant. No free kinin activity was present in the ascitic fluid. During tumor growth, kininogen levels increased in parallel with prekallikrein levels. The ascitic fluid also contained a kinin-destroying activity that was initially high during the early phase of tumor growth. Tumor cell fractions, prepared by ultracentrifugal techniques, had no kinin-forming activity while possessing kinin-destroying activity that was localized in the soluble protoplasmic protein and nuclear fractions. The kinin-forming activity of the ascitic fluid resembled that of the plasma with respect to pH optima, kinetics of kinin formation, and effect of protease inhibitors. The kininase activity of both ascitic fluid and plasma differed from that of the tumor cell fractions.", "contents": "Proteases during the growth of Ehrlich ascites tumor. II. The kallikrein-kinin system. Ascitic fluid and ascites tumor cells from Swiss mice bearing Ehrlich ascites tumor were assayed for components of the kallikrein-kinin system at various times during tumor growth. Changes in component levels were correlated with those in the plasma. Ascitic fluid contained an acetone-activated prekallikrein that increased in concentration during tumor growth and reached peak levels during the 7th-10th day post transplant. No free kinin activity was present in the ascitic fluid. During tumor growth, kininogen levels increased in parallel with prekallikrein levels. The ascitic fluid also contained a kinin-destroying activity that was initially high during the early phase of tumor growth. Tumor cell fractions, prepared by ultracentrifugal techniques, had no kinin-forming activity while possessing kinin-destroying activity that was localized in the soluble protoplasmic protein and nuclear fractions. The kinin-forming activity of the ascitic fluid resembled that of the plasma with respect to pH optima, kinetics of kinin formation, and effect of protease inhibitors. The kininase activity of both ascitic fluid and plasma differed from that of the tumor cell fractions."}
{"id": "PMID:236397", "title": "Reaction of nitrite with ascorbate and its relation to nitrosamine formation.", "content": "In this study of the nitrosation of morpholine in the presence of ascorbic acid, the amount of ascorbate required to inhibit completely the formation of nitrosomorpholine depended on whether oxygen was present in the system. The nitric oxide (produced during the oxidation of ascorbate by nitrous acid) might have reacted with oxygen to yield additional oxidizing equivalents, or oxygen might have directly oxidized the ascorbate semiquinone intermediate produced in the initial step of oxidation reaction. A pH- dependent induction period observed during the nitrosation of morpholine in the presence of ascorbate and excess nitrite was accounted for by the kinetics of the reactions.", "contents": "Reaction of nitrite with ascorbate and its relation to nitrosamine formation. In this study of the nitrosation of morpholine in the presence of ascorbic acid, the amount of ascorbate required to inhibit completely the formation of nitrosomorpholine depended on whether oxygen was present in the system. The nitric oxide (produced during the oxidation of ascorbate by nitrous acid) might have reacted with oxygen to yield additional oxidizing equivalents, or oxygen might have directly oxidized the ascorbate semiquinone intermediate produced in the initial step of oxidation reaction. A pH- dependent induction period observed during the nitrosation of morpholine in the presence of ascorbate and excess nitrite was accounted for by the kinetics of the reactions."}
{"id": "PMID:236398", "title": "Chemical studies on tobacco smoke. XXXIII. N' -nitrosonornicotine in tobacco: analysis of possible contributing factors and biologic implications.", "content": "A chemical analytic method to determine N'-nitrosonornicotine (NNN) and N' -nitrosoanabasine (NAB) in tobacco was developed. NNN was found in the unburned tobacco of commercial products at concentrations betweeen 0.3 and 88.6 mug/g. The highest levels were observed in highly fermented snuff (29.1 mug/g) and fine-cut chewing tobacco (88.6 mug/g). NAB was not detected (smaller than 0.5 ng/g) in any tobacco examined. Two new tobacco components, N' -carbomethoxynornicotine and N' -carbomethoxyanabasine,were found. Possible origins of NNN in tobacco were discussed, especially in relation to concentrations of nitrite, nitate, and alkaloids, and in relation to pH and curing. Biologic implications, including the possible function of NNN (the first organic carcinogen isolated from unburned tobacco) as a causative factor in cancer of the oral cavity in tobacco chewers and betel quid chewers, were also discussed.", "contents": "Chemical studies on tobacco smoke. XXXIII. N' -nitrosonornicotine in tobacco: analysis of possible contributing factors and biologic implications. A chemical analytic method to determine N'-nitrosonornicotine (NNN) and N' -nitrosoanabasine (NAB) in tobacco was developed. NNN was found in the unburned tobacco of commercial products at concentrations betweeen 0.3 and 88.6 mug/g. The highest levels were observed in highly fermented snuff (29.1 mug/g) and fine-cut chewing tobacco (88.6 mug/g). NAB was not detected (smaller than 0.5 ng/g) in any tobacco examined. Two new tobacco components, N' -carbomethoxynornicotine and N' -carbomethoxyanabasine,were found. Possible origins of NNN in tobacco were discussed, especially in relation to concentrations of nitrite, nitate, and alkaloids, and in relation to pH and curing. Biologic implications, including the possible function of NNN (the first organic carcinogen isolated from unburned tobacco) as a causative factor in cancer of the oral cavity in tobacco chewers and betel quid chewers, were also discussed."}
{"id": "PMID:236399", "title": "Dilutional re-expansion with crystalloid after massive hemorrahage: saline versus balanced electrolyte solution for maintenance of normal blood volume and arterial pH.", "content": "When administered in sufficient amounts, normal saline and Lactated Ringer's Solution are equally effective in maintaining adequate circulatory volumes despite severe blood loss and resultant hypoproteinemia. Arterial pH is maintained within normal limits when either solution is used for resuscitation provided the circulatory volume has been re-expanded to adequate levels for good tissue perfusion and support of aerobic metabolism. The pH of the infused solutions has no effect on blood pH under these circumstances. Fourteen splenectomized dogs were subjected to continuous hemorrhage and simultaneous replacement with either normal saline or Lactated Ringer's Solution. The cumulative replacement volume ratio necessary for equilibration after 61% RBC depletion was 7:1 crystalloid to the whole \"undiluted\" blood shed, in both groups. Indicators of pulmonary-circulatory physiology remained stable within normal limits. Arterial pH did not exhibit significant changes from normal values after resuscitation with NS or LRS. The group infused with LRS exhibited no change in arterial pH, 7.40 plus or minus .07 initial and 7.40 plus or minus .09 final; in the group with NS replacement a slight decrease from control was noted, 7.40 plus or minus .07 initial and 7.36 plus or minus .06 final. These differences, however, are not statistically significant. Of the 14 subjects, 13 were long-term survivors. The one death was associated with a technical mishap shortly after completion of the experiment. Because banked blood imposes a \"net\" alkaline metabolic load (sodium citrate), patients expected to be transfused with large volumes of stored blood might be better resuscited with normal salin than with Ringer's Lactate Soultions, to minimize or avert the otherwise resultant metabolic alkalosis.", "contents": "Dilutional re-expansion with crystalloid after massive hemorrahage: saline versus balanced electrolyte solution for maintenance of normal blood volume and arterial pH. When administered in sufficient amounts, normal saline and Lactated Ringer's Solution are equally effective in maintaining adequate circulatory volumes despite severe blood loss and resultant hypoproteinemia. Arterial pH is maintained within normal limits when either solution is used for resuscitation provided the circulatory volume has been re-expanded to adequate levels for good tissue perfusion and support of aerobic metabolism. The pH of the infused solutions has no effect on blood pH under these circumstances. Fourteen splenectomized dogs were subjected to continuous hemorrhage and simultaneous replacement with either normal saline or Lactated Ringer's Solution. The cumulative replacement volume ratio necessary for equilibration after 61% RBC depletion was 7:1 crystalloid to the whole \"undiluted\" blood shed, in both groups. Indicators of pulmonary-circulatory physiology remained stable within normal limits. Arterial pH did not exhibit significant changes from normal values after resuscitation with NS or LRS. The group infused with LRS exhibited no change in arterial pH, 7.40 plus or minus .07 initial and 7.40 plus or minus .09 final; in the group with NS replacement a slight decrease from control was noted, 7.40 plus or minus .07 initial and 7.36 plus or minus .06 final. These differences, however, are not statistically significant. Of the 14 subjects, 13 were long-term survivors. The one death was associated with a technical mishap shortly after completion of the experiment. Because banked blood imposes a \"net\" alkaline metabolic load (sodium citrate), patients expected to be transfused with large volumes of stored blood might be better resuscited with normal salin than with Ringer's Lactate Soultions, to minimize or avert the otherwise resultant metabolic alkalosis."}
{"id": "PMID:236402", "title": "Immunotherapy of malignancy in humans. Current status.", "content": "Many observations support the premise of a close relationship between immunologic competency and the growth of human cancer. Immunotherapy against cancer in animals has been established. Its function appears to be adjunctive to other treatment modalities that first lower tumor burden. These findings are demonstrated in both clinical and laboratory studies of cancer in humans. At the present time, intralesional injections of BCG vaccine in immunocompetent patients with intradermal metastases are most effective. Immunotherapy with topical administration of 2,4 dinitrochlorobenzene is the treatment of choice in selected patients with squamous or basal cell carcinoma.", "contents": "Immunotherapy of malignancy in humans. Current status. Many observations support the premise of a close relationship between immunologic competency and the growth of human cancer. Immunotherapy against cancer in animals has been established. Its function appears to be adjunctive to other treatment modalities that first lower tumor burden. These findings are demonstrated in both clinical and laboratory studies of cancer in humans. At the present time, intralesional injections of BCG vaccine in immunocompetent patients with intradermal metastases are most effective. Immunotherapy with topical administration of 2,4 dinitrochlorobenzene is the treatment of choice in selected patients with squamous or basal cell carcinoma."}
{"id": "PMID:236404", "title": "Testicular function in XYY men.", "content": "A previous survey of 48 subjects with XYY chromosome complement showed a wide scatter of values for plasma concentration of testosterone and luteinizing hormone (LH). To account for this scattering and in view of the impulsive behavior often attributed to XYY subjects, it was postulated that paroxysmal activity in the cerebral cortex produced paroxysmal stimulation at the level of the hypothalamus. To investigate this possibility, plasma concentrations of testosterone, dihydrotestosterone, follicle stimulating hormone (FSH), and LH were determined on seven consecutive days in four XYY subjects and five XY control men as well as bimonthly for four months in two XYY detainees and three XY control detainees. The variability of plasma androgen and gonadotropin levels in XYY subjects was similar to that of XY control men. The results thus do not support the above hypothesis as an explanation of the widely scattered plasma androgen values in XYY individuals. The \"XYY syndrome\" is probably heterogeneous and includes a number of patients with some degree of hypogonadism. Testicular biopsy, sperm count, and meiotic studies were carried out in eight XYY men. In one case the meiotic study showed two Y-chromatin bodies. Results of these various investigations support the diagnosis of maturation arrest of the germ cells with consequent oligospermia. Low fertility is therefore expected to be frequent among XYY subjects, although when fertilization does occur, it can result in normal XY or in XYY infants.", "contents": "Testicular function in XYY men. A previous survey of 48 subjects with XYY chromosome complement showed a wide scatter of values for plasma concentration of testosterone and luteinizing hormone (LH). To account for this scattering and in view of the impulsive behavior often attributed to XYY subjects, it was postulated that paroxysmal activity in the cerebral cortex produced paroxysmal stimulation at the level of the hypothalamus. To investigate this possibility, plasma concentrations of testosterone, dihydrotestosterone, follicle stimulating hormone (FSH), and LH were determined on seven consecutive days in four XYY subjects and five XY control men as well as bimonthly for four months in two XYY detainees and three XY control detainees. The variability of plasma androgen and gonadotropin levels in XYY subjects was similar to that of XY control men. The results thus do not support the above hypothesis as an explanation of the widely scattered plasma androgen values in XYY individuals. The \"XYY syndrome\" is probably heterogeneous and includes a number of patients with some degree of hypogonadism. Testicular biopsy, sperm count, and meiotic studies were carried out in eight XYY men. In one case the meiotic study showed two Y-chromatin bodies. Results of these various investigations support the diagnosis of maturation arrest of the germ cells with consequent oligospermia. Low fertility is therefore expected to be frequent among XYY subjects, although when fertilization does occur, it can result in normal XY or in XYY infants."}
{"id": "PMID:236425", "title": "Two forms of guanylate cyclase in mammalian tissues and possible mechanisms for their regulation.", "content": "All mammalian tissues examined to date have two forms of guanylate cyclase with apparently different properties. From the studies in several laboratories, we suggest the following mechanisms for the possible regulation of guanylate cyclase activity: (1) factors that could alter the apparent cooperative nature of the enzyme, (2) interactions of metal ions with the substrate or enzyme, (3) factors that could overcome inhibition by ATP, (4) mechanisms that could regulate the interconversion of latent and active forms of the enzyme, (5) possible translocation of particulate and soluble forms of the enzyme, and (6) induction or repression of the enzyme.", "contents": "Two forms of guanylate cyclase in mammalian tissues and possible mechanisms for their regulation. All mammalian tissues examined to date have two forms of guanylate cyclase with apparently different properties. From the studies in several laboratories, we suggest the following mechanisms for the possible regulation of guanylate cyclase activity: (1) factors that could alter the apparent cooperative nature of the enzyme, (2) interactions of metal ions with the substrate or enzyme, (3) factors that could overcome inhibition by ATP, (4) mechanisms that could regulate the interconversion of latent and active forms of the enzyme, (5) possible translocation of particulate and soluble forms of the enzyme, and (6) induction or repression of the enzyme."}
{"id": "PMID:236490", "title": "Gentamicin as a bactericidal antibiotic in tissue culture.", "content": "The effects of gentamicin on cellular physiology were studied in a total of 9 mammalian cell lines, using the following parameters: cell morphology and viability (cytotoxicity), proliferation, culture medium acidification, lactic acid production, lactate dehydrogenase release, virus susceptibility, and effects on karyotype. With regard to cytotoxicity no gross differences could be found in the sensitivity of the diploid and aneuploid cells investigated, as judged by morphological criteria. However, cells exposed to the antibiotic in the lag-log phase of growth showed damage at lower concentrations (1000 mug/ml) than cells treated in the stationary phase (2000 mug/ml). As regards the influence of gentamicin on cell growth and metabolsim, dose-response relationship were found proving that the antibiotic causes a depression of proliferation, a striking increase in lactate production, an elevated LDH release, and changes in pH behaviour. All these parameters were unaffected by concentrations up to 125 mug/ml. No gross changes in chromosome morphology and number could be detected in huploid cell line after 10 passages with 50 mug/ml gentamicin in lieu of the usual penicillin plus streptomycin combination. The minimal bactericidal concentrations (MBC) were determined in cell-free media and in tissue cultures against 4 species of bacteria. The MBC of gentamicin was generally lower as compared with the penicillin plus streptomycin combination. In some instances MBC was higher in the presence than in the absence of ti-sue culture cells. Comparison of the bactericidal efficiency against 31 strains of 7 species of bacteria of gentamicin (50 mug/ml) and penicillin plus streptomycin (100 units plus 100 mug/ml) in cell cultures proved that gentamicin is superior for control of bacterial growth in tissue culture.", "contents": "Gentamicin as a bactericidal antibiotic in tissue culture. The effects of gentamicin on cellular physiology were studied in a total of 9 mammalian cell lines, using the following parameters: cell morphology and viability (cytotoxicity), proliferation, culture medium acidification, lactic acid production, lactate dehydrogenase release, virus susceptibility, and effects on karyotype. With regard to cytotoxicity no gross differences could be found in the sensitivity of the diploid and aneuploid cells investigated, as judged by morphological criteria. However, cells exposed to the antibiotic in the lag-log phase of growth showed damage at lower concentrations (1000 mug/ml) than cells treated in the stationary phase (2000 mug/ml). As regards the influence of gentamicin on cell growth and metabolsim, dose-response relationship were found proving that the antibiotic causes a depression of proliferation, a striking increase in lactate production, an elevated LDH release, and changes in pH behaviour. All these parameters were unaffected by concentrations up to 125 mug/ml. No gross changes in chromosome morphology and number could be detected in huploid cell line after 10 passages with 50 mug/ml gentamicin in lieu of the usual penicillin plus streptomycin combination. The minimal bactericidal concentrations (MBC) were determined in cell-free media and in tissue cultures against 4 species of bacteria. The MBC of gentamicin was generally lower as compared with the penicillin plus streptomycin combination. In some instances MBC was higher in the presence than in the absence of ti-sue culture cells. Comparison of the bactericidal efficiency against 31 strains of 7 species of bacteria of gentamicin (50 mug/ml) and penicillin plus streptomycin (100 units plus 100 mug/ml) in cell cultures proved that gentamicin is superior for control of bacterial growth in tissue culture."}
{"id": "PMID:236507", "title": "Kinetic studies on the depolymerization of polyadenylic acid by ribonuclease A.", "content": "Studies were conducted on the depolymerization of polyadenylic acid (poly (A)) by RNAse A (EC 3.1.4.22) depending on the pH (pH 5-8). The results showed that depending on the pH, the ratio Vmax/Km was analogous to that described earlier for nucleoside-2', 3'-cyclophosphates and dinucleoside phosphates. This indicates that depolymerization of poly (A), transesterification and hydrolysis of specific substrates is achieved by the same ionizing groups of the enzyme with pKa 5.4 and pKb 6.4. The rate of degradation of poly (A) is also influenced by the state of adenine ionization, the protonation of which leads to the formation of a double helical poly (A), and does not serve as a substrate for RNAse A. The low rate for the depolymerization of poly (A) in the presence of RNAse A is related to a decrease in the turnover number of the enzyme, and an increase in the molecular weight of the enzyme (RNAse dimer), leads to a decrease in the Km, and does not effect Vmax. This indicates that the rate of depolymerization of polynucleotides is determined by orientation of factors. On the basis of the comparison of the resultant kinetic data, and the structure of the enzyme inhibitory complexes of RNAse S, which were studied by the method of x-ray structural analysis, a conclusion was reached on the kinetic characteristics of RNAse A specificity with respect to polymeric substrates, which is determined by the orinetation of the ribose phosphate relative to the catalytic groups of the active site.", "contents": "Kinetic studies on the depolymerization of polyadenylic acid by ribonuclease A. Studies were conducted on the depolymerization of polyadenylic acid (poly (A)) by RNAse A (EC 3.1.4.22) depending on the pH (pH 5-8). The results showed that depending on the pH, the ratio Vmax/Km was analogous to that described earlier for nucleoside-2', 3'-cyclophosphates and dinucleoside phosphates. This indicates that depolymerization of poly (A), transesterification and hydrolysis of specific substrates is achieved by the same ionizing groups of the enzyme with pKa 5.4 and pKb 6.4. The rate of degradation of poly (A) is also influenced by the state of adenine ionization, the protonation of which leads to the formation of a double helical poly (A), and does not serve as a substrate for RNAse A. The low rate for the depolymerization of poly (A) in the presence of RNAse A is related to a decrease in the turnover number of the enzyme, and an increase in the molecular weight of the enzyme (RNAse dimer), leads to a decrease in the Km, and does not effect Vmax. This indicates that the rate of depolymerization of polynucleotides is determined by orientation of factors. On the basis of the comparison of the resultant kinetic data, and the structure of the enzyme inhibitory complexes of RNAse S, which were studied by the method of x-ray structural analysis, a conclusion was reached on the kinetic characteristics of RNAse A specificity with respect to polymeric substrates, which is determined by the orinetation of the ribose phosphate relative to the catalytic groups of the active site."}
{"id": "PMID:236508", "title": "Investigation of the conformational lability of serum albumin macromolecules in aqueous solution by the NMR spin-echo method.", "content": "The complex proton spin-echo decay curve was recorded for human serum albumin (SA) solutions with different concentrations in normal and heavy water. The curve included three fast-decaying components for SA, in addition to the slow-decaying component for the water. The total amplitude of these three components roughly corresponded to the number of protons in the SA (with isotopic exchange taken into account); the component ratio remained constant at different concentrations and different temperatures between 4 and 39 degrees. The relatively slow-decaying protein component, which accounted for similar to 10% of the SA protons, was produced by the side chains of the protein. The presence of two other faster-decaying SA components with approximately equal amplitudes indicated that only about half of the remaining protons in the SA macromolecule are incorporated into the comparatively rigid globule, the other half belonging to groups with high conformational lability in aqueous solution. The activation energy for the aqueous component was close to that for pure water, while the activation energies for the protein components were roughly twice as large.", "contents": "Investigation of the conformational lability of serum albumin macromolecules in aqueous solution by the NMR spin-echo method. The complex proton spin-echo decay curve was recorded for human serum albumin (SA) solutions with different concentrations in normal and heavy water. The curve included three fast-decaying components for SA, in addition to the slow-decaying component for the water. The total amplitude of these three components roughly corresponded to the number of protons in the SA (with isotopic exchange taken into account); the component ratio remained constant at different concentrations and different temperatures between 4 and 39 degrees. The relatively slow-decaying protein component, which accounted for similar to 10% of the SA protons, was produced by the side chains of the protein. The presence of two other faster-decaying SA components with approximately equal amplitudes indicated that only about half of the remaining protons in the SA macromolecule are incorporated into the comparatively rigid globule, the other half belonging to groups with high conformational lability in aqueous solution. The activation energy for the aqueous component was close to that for pure water, while the activation energies for the protein components were roughly twice as large."}
{"id": "PMID:236510", "title": "Pyruvate kinase from human skeletal muscle.", "content": "A simple method is described for the isolation of crystalline pyruvate kinase from human skeletal muscle. The enzyme was purified by ammonium sulfate fractionation, heat treatment and crystallization. Two crystal forms of pyruvate kinase differing in solubility but not in specific activity were found. The homogenous enzyme preparations in triethanolamine buffer, pH 7.6 reveal at 25 degrees a specific activity of 245 U per mg protein, and of 340 U/mg in potassium phosphate buffer (50 mM). The enzyme is activated by inorganic phosphate and fructosediphosphate to the same extent, and inhibited non competetively by ammonium ion. The molecular weight as measured by gel filtration is 220,000 daltons and the enzyme molecule is composed of 4 subunits.", "contents": "Pyruvate kinase from human skeletal muscle. A simple method is described for the isolation of crystalline pyruvate kinase from human skeletal muscle. The enzyme was purified by ammonium sulfate fractionation, heat treatment and crystallization. Two crystal forms of pyruvate kinase differing in solubility but not in specific activity were found. The homogenous enzyme preparations in triethanolamine buffer, pH 7.6 reveal at 25 degrees a specific activity of 245 U per mg protein, and of 340 U/mg in potassium phosphate buffer (50 mM). The enzyme is activated by inorganic phosphate and fructosediphosphate to the same extent, and inhibited non competetively by ammonium ion. The molecular weight as measured by gel filtration is 220,000 daltons and the enzyme molecule is composed of 4 subunits."}
{"id": "PMID:236511", "title": "A new two-dimensional gel electrophoresis system for the analysis of complex protein mixtures: application to the ribosome of E. coli.", "content": "A new method for two-dimensional polyacrylamide gel electrophoresis of proteins is described. The method, illustrated here by its application for the analysis of ribosomal proteins of E. coli, has a high resolving power. The proteins S15 and S16 can be resolved either following alkylation or under reducing conditions. This was not possible with urea gel systems previously employed. The method should be advantageous in the identification of the components of dimers formed with the reagent methyl 4-mercaptobutyrimidate. An additional advantage of the new method is that both dimensions are run at an acidic pH. For ribosomal proteins it is therefore unnecessary to either polymerize the protein sample in the middle of the first dimension disc gel or to electrophorese two samples with opposite polarity.", "contents": "A new two-dimensional gel electrophoresis system for the analysis of complex protein mixtures: application to the ribosome of E. coli. A new method for two-dimensional polyacrylamide gel electrophoresis of proteins is described. The method, illustrated here by its application for the analysis of ribosomal proteins of E. coli, has a high resolving power. The proteins S15 and S16 can be resolved either following alkylation or under reducing conditions. This was not possible with urea gel systems previously employed. The method should be advantageous in the identification of the components of dimers formed with the reagent methyl 4-mercaptobutyrimidate. An additional advantage of the new method is that both dimensions are run at an acidic pH. For ribosomal proteins it is therefore unnecessary to either polymerize the protein sample in the middle of the first dimension disc gel or to electrophorese two samples with opposite polarity."}
{"id": "PMID:236512", "title": "[LH-RH Test in prepuberal children (author's transl)].", "content": "The LH-RH test was performed in 62 mainly prepuberal children. A dose of 25 mug/20 kg was given intravenously between 10 and 12a.m. Prepuberal healthy boys between 1 11/12 and 9 7/12 years of age reacted with a fourhold increase of LH. Prepuberal boys with an unilaterally undescended testicle showed no difference in LH response from normal. Even a low increase in LH may be followed by spontaneous puberty in children with pituitary dwarfism. The LH response in children with craniopharyngeoma was heterogeneous and appeared to depend on location of tumor and extent of operation. Birdheaded dwarfism and small stature due to steroid administration and due to unknown etiology showed normal LH responses for age. Cases with anorchia and myotonic dystrophy had an excessive LH increase. The LH response in children with Fanconi's anemia and undescended testicles and in otherwise healthy boys with undescended testicles was normal for age. A case of untreated adrenogenital syndrome without salt loss had a presumably normal increase of LH when related to bone age. Primary and pituitary hypothyroidism was shown to have a higher than normal output of LH. A boy with a tumor the 3rd ventricle hat basal levels of LH that were extremely elevated and associated with precocious puberty and diabetes insipidus. A newborn infant with anencephalus showed no increase of LH and LH-RH injection.", "contents": "[LH-RH Test in prepuberal children (author's transl)]. The LH-RH test was performed in 62 mainly prepuberal children. A dose of 25 mug/20 kg was given intravenously between 10 and 12a.m. Prepuberal healthy boys between 1 11/12 and 9 7/12 years of age reacted with a fourhold increase of LH. Prepuberal boys with an unilaterally undescended testicle showed no difference in LH response from normal. Even a low increase in LH may be followed by spontaneous puberty in children with pituitary dwarfism. The LH response in children with craniopharyngeoma was heterogeneous and appeared to depend on location of tumor and extent of operation. Birdheaded dwarfism and small stature due to steroid administration and due to unknown etiology showed normal LH responses for age. Cases with anorchia and myotonic dystrophy had an excessive LH increase. The LH response in children with Fanconi's anemia and undescended testicles and in otherwise healthy boys with undescended testicles was normal for age. A case of untreated adrenogenital syndrome without salt loss had a presumably normal increase of LH when related to bone age. Primary and pituitary hypothyroidism was shown to have a higher than normal output of LH. A boy with a tumor the 3rd ventricle hat basal levels of LH that were extremely elevated and associated with precocious puberty and diabetes insipidus. A newborn infant with anencephalus showed no increase of LH and LH-RH injection."}
{"id": "PMID:236513", "title": "Renin release, saralasin and the vasodilator-beta-blocker drug interaction in man.", "content": "Saralasin, an angiotensin antagonist, was used to study the role of renin-angiotensin in the vasodilator-beta-blocker drug interaction in hypertensive subjects. Plasma renin activity was elevated by withdrawal of propranolol in seven patients using minoxidil and propranolol. After propranolol withdrawal, saralasin caused hypotension (100/60 mm Hg or less) in five. Propranolol lowered blood pressure and plasma renin activity and diminished the hypotensive response to saralasin. Saralasin induced renin release in all patients, an effect blocked by propranolol. We conclude that angiotensin can be the major determinant of blood pressure in vasodilator-drug treated patients, that propranolol lowering of blood pressure in this vasodilator-beta-blocker drug interaction is related to suppression of renin release, and that the angiotensin feed-back-suppression mechanism for inhibiting renin release in functionally located proximal to beta-adrenergic receptors mediating renin release.", "contents": "Renin release, saralasin and the vasodilator-beta-blocker drug interaction in man. Saralasin, an angiotensin antagonist, was used to study the role of renin-angiotensin in the vasodilator-beta-blocker drug interaction in hypertensive subjects. Plasma renin activity was elevated by withdrawal of propranolol in seven patients using minoxidil and propranolol. After propranolol withdrawal, saralasin caused hypotension (100/60 mm Hg or less) in five. Propranolol lowered blood pressure and plasma renin activity and diminished the hypotensive response to saralasin. Saralasin induced renin release in all patients, an effect blocked by propranolol. We conclude that angiotensin can be the major determinant of blood pressure in vasodilator-drug treated patients, that propranolol lowering of blood pressure in this vasodilator-beta-blocker drug interaction is related to suppression of renin release, and that the angiotensin feed-back-suppression mechanism for inhibiting renin release in functionally located proximal to beta-adrenergic receptors mediating renin release."}
{"id": "PMID:236514", "title": "A career in ambulatory medicine.", "content": "To meet the need and resolve long standing conflicts in the delivery of primary care in an age of specialization, I propose an experiment with a different type of primary medical education based on the separation of careers into community-oriented primary and continuing care of ambulatory patients and hospital-based intensive care of acutely ill bed patients. High-school graduates selected for interest, aptitude, and personality would follow a six-year pathway through college and medical school. A singular feature of the proposal would be the replacement of bedside training with an undergraduate traineeship of two to 2 1/2 years in the hospital ambulatory specialty clinics, emergency clinic, and a primary-care model practice unit, followed by a one-year externship in this primary-care center. The graduate would be oriented toward group and team practice and would work in a system integrating primary, secondary, and tertiary care.", "contents": "A career in ambulatory medicine. To meet the need and resolve long standing conflicts in the delivery of primary care in an age of specialization, I propose an experiment with a different type of primary medical education based on the separation of careers into community-oriented primary and continuing care of ambulatory patients and hospital-based intensive care of acutely ill bed patients. High-school graduates selected for interest, aptitude, and personality would follow a six-year pathway through college and medical school. A singular feature of the proposal would be the replacement of bedside training with an undergraduate traineeship of two to 2 1/2 years in the hospital ambulatory specialty clinics, emergency clinic, and a primary-care model practice unit, followed by a one-year externship in this primary-care center. The graduate would be oriented toward group and team practice and would work in a system integrating primary, secondary, and tertiary care."}
{"id": "PMID:236517", "title": "The congress and health manpower: a legislative morass.", "content": "To correct deficiencies in physicians' services, chiefly related to geographic maldistribution and overspecialization, numerous bills have been introduced in both the House and the Senate. These bills would increase the annual number of medical graduates, would mandate service in areas defined as lacking in physicians, and would promote the training of primary-care physicians as opposed to more specialized training. The number of foreign medical graduates would also be restricted. Almost all this legislation potentially may diminish the quality of medical education without substantially affecting the provision of health service. Recently introduced legislation (HR 3279), however, seems to deal more rationally with the problems of health manpower.", "contents": "The congress and health manpower: a legislative morass. To correct deficiencies in physicians' services, chiefly related to geographic maldistribution and overspecialization, numerous bills have been introduced in both the House and the Senate. These bills would increase the annual number of medical graduates, would mandate service in areas defined as lacking in physicians, and would promote the training of primary-care physicians as opposed to more specialized training. The number of foreign medical graduates would also be restricted. Almost all this legislation potentially may diminish the quality of medical education without substantially affecting the provision of health service. Recently introduced legislation (HR 3279), however, seems to deal more rationally with the problems of health manpower."}
{"id": "PMID:236522", "title": "Clinical aspects of bilateral renal dysplasia in children.", "content": "Despite recent attempts to improve classification and to provide data on pathogenic mechanisms, there is a paucity of information concerning the clinical aspects of bilateral renal dysplasia.  Therefore, the clinical features and long-term prognosis of eight patients with bilateral renal dysplasia have been evaluated.  Three important observations were made, namely (1) a large proportion of patients had an impairment of urinary concentration and acidification, (2) the clinical course was characterized by progressive renal deterioration in patients with bilateral involvement, and (3) four children with renal dysplasia had the clinical features of Laurence-Moon-Biedl syndrome.", "contents": "Clinical aspects of bilateral renal dysplasia in children. Despite recent attempts to improve classification and to provide data on pathogenic mechanisms, there is a paucity of information concerning the clinical aspects of bilateral renal dysplasia.  Therefore, the clinical features and long-term prognosis of eight patients with bilateral renal dysplasia have been evaluated.  Three important observations were made, namely (1) a large proportion of patients had an impairment of urinary concentration and acidification, (2) the clinical course was characterized by progressive renal deterioration in patients with bilateral involvement, and (3) four children with renal dysplasia had the clinical features of Laurence-Moon-Biedl syndrome."}
{"id": "PMID:236525", "title": "[Anti-platelet aggregating drugs in the prevention of thromboembolic diseases].", "content": "The treatment and prevention of arterial thrombosis have been improved in recent years by the use of drugs acting on certain platelet characteristics, such as clumping capacity, adhesivity, release of factors 3 & 4, and survival.  Many substances have been proposed for clinical employment.  Mechanisms of action are discussed on the basis of personal experience, particularly with dipyrimadol and beta-blocking drugs.  It would seem that the best results are obtainable with drugs whose effect on platelet clumping comes from stablisation of the membrane, such as the non-steroid anti-inflammatory preparations, in association with drugs than enhance intraplatelet cyclic AMP.", "contents": "[Anti-platelet aggregating drugs in the prevention of thromboembolic diseases]. The treatment and prevention of arterial thrombosis have been improved in recent years by the use of drugs acting on certain platelet characteristics, such as clumping capacity, adhesivity, release of factors 3 & 4, and survival.  Many substances have been proposed for clinical employment.  Mechanisms of action are discussed on the basis of personal experience, particularly with dipyrimadol and beta-blocking drugs.  It would seem that the best results are obtainable with drugs whose effect on platelet clumping comes from stablisation of the membrane, such as the non-steroid anti-inflammatory preparations, in association with drugs than enhance intraplatelet cyclic AMP."}
{"id": "PMID:236526", "title": "[Verapamil in the study and treatment of supraventricular tachycardias, with special reference to pre-excitation].", "content": "Verapamil is a novel antiarrhythmic agent which appears to act as a calcium-ion antagonist, blocking calcium transport across the myocardial cell membrane. It was given intravenously, in a dose of 10 mg, to thirty-two patients suffering from paroxysmal supraventricular tachycardia, and sinus rhythm was achieved promptly in all. Identical results were obtained in a further ten patients with supraventricular tachycardias associated with the Wolff-Parkinson-White or other pre-excitation syndromes. In a separate group of eighteen patients in whom A-V junctional tachycardias were induced during intracardiac electrography, conversion to sinus rhythm was achieved in fifteen patients, with prolongation of the cycle length in the others. Circus-movement tachycardias were induced in eight patients with the Wolff-Parkinson-White syndrome, and conversion to sinus rhythm was achieved in seven. The results were less consistent in patients with other supraventricular arrhythmias including ectopic atrial tachycardia and atrial flutter, and, in the single patient with supraventricular and ventricular tachycardias, only the former was controlled. In the single patient with atrial fibrillation complicating the wolff-Parkinson-White syndrome who received Verapamil, sinus rhythm was restored. Side effects were few and mild, with rare exceptions of profound hypotension, bradycardia and asystole; their management is discussed, and reasons are advanced why their occurrence is likely to be related either to the concomitant administration of beta-adrenergic blockers or to the presence of sinoatrial disease. It appears that Verapamil is particularly suitable for the treatment of supraventricular tachycardias due to a circus movement as calcium antagonism is likely to be most effective in the N region of the atrioventricular node.", "contents": "[Verapamil in the study and treatment of supraventricular tachycardias, with special reference to pre-excitation]. Verapamil is a novel antiarrhythmic agent which appears to act as a calcium-ion antagonist, blocking calcium transport across the myocardial cell membrane. It was given intravenously, in a dose of 10 mg, to thirty-two patients suffering from paroxysmal supraventricular tachycardia, and sinus rhythm was achieved promptly in all. Identical results were obtained in a further ten patients with supraventricular tachycardias associated with the Wolff-Parkinson-White or other pre-excitation syndromes. In a separate group of eighteen patients in whom A-V junctional tachycardias were induced during intracardiac electrography, conversion to sinus rhythm was achieved in fifteen patients, with prolongation of the cycle length in the others. Circus-movement tachycardias were induced in eight patients with the Wolff-Parkinson-White syndrome, and conversion to sinus rhythm was achieved in seven. The results were less consistent in patients with other supraventricular arrhythmias including ectopic atrial tachycardia and atrial flutter, and, in the single patient with supraventricular and ventricular tachycardias, only the former was controlled. In the single patient with atrial fibrillation complicating the wolff-Parkinson-White syndrome who received Verapamil, sinus rhythm was restored. Side effects were few and mild, with rare exceptions of profound hypotension, bradycardia and asystole; their management is discussed, and reasons are advanced why their occurrence is likely to be related either to the concomitant administration of beta-adrenergic blockers or to the presence of sinoatrial disease. It appears that Verapamil is particularly suitable for the treatment of supraventricular tachycardias due to a circus movement as calcium antagonism is likely to be most effective in the N region of the atrioventricular node."}
{"id": "PMID:236528", "title": "A double blind trial of nitrazepam and flurazepam as sedatives.", "content": "A double-blind cross-over trial was conducted using flurazepam and nitrazepam as sedatives in a group of a dozen psychiatric in-patients. The results show highly significant differences between placebo effects and the active drugs. The differences between the two drugs were not significant apart from the subjective estimate of time slept in which flurazepam was superior. As other studies have confirmed also their safety, relative lack of side effects and very low addictive potential it seems there is little to choose between them, except for the possibility that flurazepam may be preferred subjectively.", "contents": "A double blind trial of nitrazepam and flurazepam as sedatives. A double-blind cross-over trial was conducted using flurazepam and nitrazepam as sedatives in a group of a dozen psychiatric in-patients. The results show highly significant differences between placebo effects and the active drugs. The differences between the two drugs were not significant apart from the subjective estimate of time slept in which flurazepam was superior. As other studies have confirmed also their safety, relative lack of side effects and very low addictive potential it seems there is little to choose between them, except for the possibility that flurazepam may be preferred subjectively."}
{"id": "PMID:236531", "title": "[Gasometric determination of total CO2 using and adapted syringe].", "content": "It seemed to us interesting to study the results supplied by a new apparatus designed for gasometric estimation of total CO2 in biological fluids according to a technique derived from that of Van Slyke. The main qualities observed are: linearity (10 to 40 mM/l); rapidly (20 estimations in 35 minutes), reliability (coefficient of variation 1.6% over 15 estimations), daily reproducibility (2 standard deviations = 2 mM/l), satisfactory correlation with a colorimetric method using orthocresolphtalein adapted to SMA 6/60 (r = 0.90) and with an indirect method leading to total CO2 levels by calculation from pH and pCO2 (r = 0.92). However, this technique is difficult to use in pediatrics for the samples of plasma cannot be less than 0.5 ml.", "contents": "[Gasometric determination of total CO2 using and adapted syringe]. It seemed to us interesting to study the results supplied by a new apparatus designed for gasometric estimation of total CO2 in biological fluids according to a technique derived from that of Van Slyke. The main qualities observed are: linearity (10 to 40 mM/l); rapidly (20 estimations in 35 minutes), reliability (coefficient of variation 1.6% over 15 estimations), daily reproducibility (2 standard deviations = 2 mM/l), satisfactory correlation with a colorimetric method using orthocresolphtalein adapted to SMA 6/60 (r = 0.90) and with an indirect method leading to total CO2 levels by calculation from pH and pCO2 (r = 0.92). However, this technique is difficult to use in pediatrics for the samples of plasma cannot be less than 0.5 ml."}
{"id": "PMID:236533", "title": "Growth retardation in children with ulcerative colitis: the effect of medical and surgical therapy.", "content": "The growth of 37 children with ulcerative colitis have been analyzed. While conventional growth charts showed only percentile changes in height, height data plotted on Tanner et al.'s growth charts showed increases and decreases in growth velocity. Growth retardation is a prominent complication of ulcerative colitis with onset on bowel symptoms. Both ulcerative colitis and \"high-dose\" steroid therapy (greater than 12 mg/sq m/day of cortisol) can hinder growth but in some instances there is a growth spurt after high-dose steroid therapy. \"Low-dose\" steroid therapy does not retard growth. Colectomy is more effective than high-dose steroid therapy in reversing the growth retardation caused by ulcerative colitis and is of greatest value if not delayed too long. Growth following subtotal colectomy with ileorectal anastomosis (Aylett procedure) is not likely to be as much as that after subtotal colectomy with ileostomy. Growth retardation is infrequently the only indication for surgical intervention but ileostomy and colectomy are appropriate for this complication of ulcertive colitis in itself when not improved by adequate medical treatment.", "contents": "Growth retardation in children with ulcerative colitis: the effect of medical and surgical therapy. The growth of 37 children with ulcerative colitis have been analyzed. While conventional growth charts showed only percentile changes in height, height data plotted on Tanner et al.'s growth charts showed increases and decreases in growth velocity. Growth retardation is a prominent complication of ulcerative colitis with onset on bowel symptoms. Both ulcerative colitis and \"high-dose\" steroid therapy (greater than 12 mg/sq m/day of cortisol) can hinder growth but in some instances there is a growth spurt after high-dose steroid therapy. \"Low-dose\" steroid therapy does not retard growth. Colectomy is more effective than high-dose steroid therapy in reversing the growth retardation caused by ulcerative colitis and is of greatest value if not delayed too long. Growth following subtotal colectomy with ileorectal anastomosis (Aylett procedure) is not likely to be as much as that after subtotal colectomy with ileostomy. Growth retardation is infrequently the only indication for surgical intervention but ileostomy and colectomy are appropriate for this complication of ulcertive colitis in itself when not improved by adequate medical treatment."}
{"id": "PMID:236534", "title": "Pneumothorax and pneumomediastinum in infants with idiopathic respiratory distress syndrome receiving continuous positive airway pressure.", "content": "A review of infants with idiopathic respiratory distress syndrome developing pneumomediastinum and pneumothorax reveals (1) an incidence of 20% in patients receiving CPAP with an 11% incidence in comparable infants not receiving this mode of therapy; (2) in the CPAP-treated group the occurrence was at a stage in the illness when the inspired oxygen concentration was being lowered and when ventilation was stable; (3) the inspired oxygen concentration in the CPAP group at the time of the PM and/or PT was 52% (plus or minus S.D. 15%) at a mean age of 33 hours (plus or minus S.D. 23 hr). These observations suggest that distending airway pressure creates excessive alveolar distention as an underlying mechanism of the air leak. It is recommended that distending airway pressure be lowered prior to achieving an inspried oxygen concentration of 60%. A controlled study is in progress to delineate the optimum distending airway pressures at specific inspired oxygen concentrations in order to reduce the incidence of alveolar rupture to a minimum.", "contents": "Pneumothorax and pneumomediastinum in infants with idiopathic respiratory distress syndrome receiving continuous positive airway pressure. A review of infants with idiopathic respiratory distress syndrome developing pneumomediastinum and pneumothorax reveals (1) an incidence of 20% in patients receiving CPAP with an 11% incidence in comparable infants not receiving this mode of therapy; (2) in the CPAP-treated group the occurrence was at a stage in the illness when the inspired oxygen concentration was being lowered and when ventilation was stable; (3) the inspired oxygen concentration in the CPAP group at the time of the PM and/or PT was 52% (plus or minus S.D. 15%) at a mean age of 33 hours (plus or minus S.D. 23 hr). These observations suggest that distending airway pressure creates excessive alveolar distention as an underlying mechanism of the air leak. It is recommended that distending airway pressure be lowered prior to achieving an inspried oxygen concentration of 60%. A controlled study is in progress to delineate the optimum distending airway pressures at specific inspired oxygen concentrations in order to reduce the incidence of alveolar rupture to a minimum."}
{"id": "PMID:236535", "title": "Prevention of apnea and bradycardia in low-birthweight infants.", "content": "The efficacy of theophylline in preventing severe apnea was evaluated in 17 low-birthweight infants (mean weight, 1,400 gm).  Apnea was detected and accurately quantified by 13-hour pneumogram recordings and correlated with serum theophylline levels.  Nursing observations coupled with on-line alarm systems detected only 39% of severe apneic episodes as compared to the pneumogram recording technique.  Theophylline in six hourly oral doses(1.5 to 4.0 mg/kg) yielded two-hour serum concentrations of 6.6 to 11.0 mug/ml which completely controlled apneic spells exceeding 20 seconds in duration and markedly reduced 10- 19-second apneic episodes and any resultant bradycardia.  At these serum levels, toxicity was not observed.  Therapy with theophylline should be instituted at a dose of 2 to 3 mg/kg every six hours and the optimum therapeutic dose should be individualized as determined by objective quantitation of apnea and serum theophylline concentration.", "contents": "Prevention of apnea and bradycardia in low-birthweight infants. The efficacy of theophylline in preventing severe apnea was evaluated in 17 low-birthweight infants (mean weight, 1,400 gm).  Apnea was detected and accurately quantified by 13-hour pneumogram recordings and correlated with serum theophylline levels.  Nursing observations coupled with on-line alarm systems detected only 39% of severe apneic episodes as compared to the pneumogram recording technique.  Theophylline in six hourly oral doses(1.5 to 4.0 mg/kg) yielded two-hour serum concentrations of 6.6 to 11.0 mug/ml which completely controlled apneic spells exceeding 20 seconds in duration and markedly reduced 10- 19-second apneic episodes and any resultant bradycardia.  At these serum levels, toxicity was not observed.  Therapy with theophylline should be instituted at a dose of 2 to 3 mg/kg every six hours and the optimum therapeutic dose should be individualized as determined by objective quantitation of apnea and serum theophylline concentration."}
{"id": "PMID:236536", "title": "Laryngeal chemosensitivity: a possible mechanism for sudden infant death.", "content": "In 32 anaesthetized piglets 1 to 42 days of age the distal trachea was cannulated and pressure changes were recorded.  The proximal trachea was cannulated for introduction of test fluids into the laryngeal area.  Arterial pressure, heart rate, and central venous pressure were continuously recorded.  Arterial blood samples were obtained at intervals and analyzed for PO2, PCO2, pH, and hematocrit.  Normal saline produced no, or brief, transitory alterations of the respiratory pattern and arterial pressure.  In contrast, instillation of distilled water produced apnea in 29 of 30 piglets.  In 20 the apnea was sustained.  Eleven died within approximately 50 minutes of asphyxia.  An additional nine were expected to die with continuing apnea (PO2, 10 to 15 mm Hg; PCO2 greater than 100 mm Hg; pH smaller than 6.8) but the sequence was interrupted by replacement of water with saline.  Twenty-three of 29 piglets showed an apneic response to cow's milk similar to that seen with distilled water.  Seven died of asphyxia and an additional three showed sustained respiratory inhibition until milk was replaced with saline.  The responses were completely abolished by superior laryngeal nerve (SLN) sectioning.  Electrical stimulation of the SLN produced sustained apnea in seven of eight piglets tested.  Studies in two 3-day-old lambs showed similar discrimination but only transitory apnea with water or cow's milk.  Both died during SLN stimulation.  Two ewes showed insignificant responses.  These findings suggest a lethal reflex mechanism with implications for the SIDS problem.", "contents": "Laryngeal chemosensitivity: a possible mechanism for sudden infant death. In 32 anaesthetized piglets 1 to 42 days of age the distal trachea was cannulated and pressure changes were recorded.  The proximal trachea was cannulated for introduction of test fluids into the laryngeal area.  Arterial pressure, heart rate, and central venous pressure were continuously recorded.  Arterial blood samples were obtained at intervals and analyzed for PO2, PCO2, pH, and hematocrit.  Normal saline produced no, or brief, transitory alterations of the respiratory pattern and arterial pressure.  In contrast, instillation of distilled water produced apnea in 29 of 30 piglets.  In 20 the apnea was sustained.  Eleven died within approximately 50 minutes of asphyxia.  An additional nine were expected to die with continuing apnea (PO2, 10 to 15 mm Hg; PCO2 greater than 100 mm Hg; pH smaller than 6.8) but the sequence was interrupted by replacement of water with saline.  Twenty-three of 29 piglets showed an apneic response to cow's milk similar to that seen with distilled water.  Seven died of asphyxia and an additional three showed sustained respiratory inhibition until milk was replaced with saline.  The responses were completely abolished by superior laryngeal nerve (SLN) sectioning.  Electrical stimulation of the SLN produced sustained apnea in seven of eight piglets tested.  Studies in two 3-day-old lambs showed similar discrimination but only transitory apnea with water or cow's milk.  Both died during SLN stimulation.  Two ewes showed insignificant responses.  These findings suggest a lethal reflex mechanism with implications for the SIDS problem."}
{"id": "PMID:236545", "title": "[Serum gamma-glutamyl-transpeptidase and alcoholism. Diagnosis and control of withdrawal].", "content": "The gammaGT of a generally healthy population is abnormally high due to the presence of ethanol in the diet. We confirm Rosalki's finding that a high proportion of alchoholics show an increased gammaGT activity. After alcohol deprivation, the gammaGT of alcoholics decreases in the first few days according to an exponential law with a half-time of return to normal of 5-17 days. Among past alcoholics, those who stopped drinking for a year have a lower GT activity (mean: 21 mU/ml) than a generally healthy population and in the range of Szasz's reference values. Alcoholics who did not stop drinking have a higher gammaGT activity (mean: 172). Ascitic cirrhotics who drink at least 1 liter of wine per day have also a high activity (mean: 139) while those who stopped drinking for at least 2 months have a much lower activity (mean: 49) and those who stopped for a year a normal activity. In 10 out of 11 alcoholic cirrhotics who stopped drinking, the gammaGT decreased (half-time: 11-54 days). These results show that the determination of gammaGT activity is a good test for the detection of ethanol impregnation.", "contents": "[Serum gamma-glutamyl-transpeptidase and alcoholism. Diagnosis and control of withdrawal]. The gammaGT of a generally healthy population is abnormally high due to the presence of ethanol in the diet. We confirm Rosalki's finding that a high proportion of alchoholics show an increased gammaGT activity. After alcohol deprivation, the gammaGT of alcoholics decreases in the first few days according to an exponential law with a half-time of return to normal of 5-17 days. Among past alcoholics, those who stopped drinking for a year have a lower GT activity (mean: 21 mU/ml) than a generally healthy population and in the range of Szasz's reference values. Alcoholics who did not stop drinking have a higher gammaGT activity (mean: 172). Ascitic cirrhotics who drink at least 1 liter of wine per day have also a high activity (mean: 139) while those who stopped drinking for at least 2 months have a much lower activity (mean: 49) and those who stopped for a year a normal activity. In 10 out of 11 alcoholic cirrhotics who stopped drinking, the gammaGT decreased (half-time: 11-54 days). These results show that the determination of gammaGT activity is a good test for the detection of ethanol impregnation."}
{"id": "PMID:236547", "title": "Protonated polynucleotide structures.  16. Thermodynamics of the melting of the acid form of polycytidylic acid.", "content": "A phase diagram (pH, ionic strength, temperature) for the double helical form of poly(C) is presented. The thermo-dynamic analysis of these data shows that poly(C) behaves essentially as cytidine, if the electrostatic (ionic strength) contributions and the free energy of double helix formation are considered and taken into account.", "contents": "Protonated polynucleotide structures.  16. Thermodynamics of the melting of the acid form of polycytidylic acid. A phase diagram (pH, ionic strength, temperature) for the double helical form of poly(C) is presented. The thermo-dynamic analysis of these data shows that poly(C) behaves essentially as cytidine, if the electrostatic (ionic strength) contributions and the free energy of double helix formation are considered and taken into account."}
{"id": "PMID:236548", "title": "Size fractionation of double-stranded DNA by precipitation with polyethylene glycol.", "content": "We show that DNA molecules of differing molecular mass are separable by selective precipitation with polyethylene glycol (PEG+.. Higher molecular mass DNA precipitates at lower PEG concentrations than lower molecular mass DNA. Double-stranded DNA can be fractionated at least in the range of 3 times 10-7 to 1 times 10-5 daltons. The effects on PEG concentration, sodium chloride concentration, DNA concentration, pH, divalent ions, precipitation time, and centrifugal force have been determined. These studies show PEG precipitation offers a size fractionation method for DNA which is convenient, of high capacity, and applicable over a wide range of conditions. However, resolution is not high and separation of two species approaches 100% only if they differ in molecular mass by at least a factor of two.", "contents": "Size fractionation of double-stranded DNA by precipitation with polyethylene glycol. We show that DNA molecules of differing molecular mass are separable by selective precipitation with polyethylene glycol (PEG+.. Higher molecular mass DNA precipitates at lower PEG concentrations than lower molecular mass DNA. Double-stranded DNA can be fractionated at least in the range of 3 times 10-7 to 1 times 10-5 daltons. The effects on PEG concentration, sodium chloride concentration, DNA concentration, pH, divalent ions, precipitation time, and centrifugal force have been determined. These studies show PEG precipitation offers a size fractionation method for DNA which is convenient, of high capacity, and applicable over a wide range of conditions. However, resolution is not high and separation of two species approaches 100% only if they differ in molecular mass by at least a factor of two."}
{"id": "PMID:236549", "title": "Transfer RNA methyltransferases from yellow lupin seeds: purification and properties.", "content": "tRNA methyltransferases from extract of yellow lupin seeds were purified over 300-fold by the methods based on hydrophobic and affinity chromatography. However, in the most active fractions the methylating enzymes were over 2000 purified. The purified enzyme fractions catalysed the formation of 1-methyladenine and 5-methylcytosine using E. coli B and B. subtilis tRNAs as substrates and S-adenosylmethionine as the methyl donor. They were unable to methylate their own endogenous tRNA but they were capable of methylating tRNA of some other lupinus species. Whereas the patterns of methylated constituents of tRNA of some other lupinus and B. subtilis were quite similar, they differed considerably from those obtained with lupin species tRNAs. Some properties of purified methyltransferases from yellow lupin seeds have been described.", "contents": "Transfer RNA methyltransferases from yellow lupin seeds: purification and properties. tRNA methyltransferases from extract of yellow lupin seeds were purified over 300-fold by the methods based on hydrophobic and affinity chromatography. However, in the most active fractions the methylating enzymes were over 2000 purified. The purified enzyme fractions catalysed the formation of 1-methyladenine and 5-methylcytosine using E. coli B and B. subtilis tRNAs as substrates and S-adenosylmethionine as the methyl donor. They were unable to methylate their own endogenous tRNA but they were capable of methylating tRNA of some other lupinus species. Whereas the patterns of methylated constituents of tRNA of some other lupinus and B. subtilis were quite similar, they differed considerably from those obtained with lupin species tRNAs. Some properties of purified methyltransferases from yellow lupin seeds have been described."}
{"id": "PMID:236550", "title": "The interaction of ribonuclease T 1 with DNA.", "content": "The interaction of RNase T1 with calf thymus DNA was studied using uv difference spectroscopy and the effect of the enzyme on DNA melting. There was no indication of RNase T1 binding with native DNA. A prominent difference spectrum for RNase T1 binding with denatured DNA (d-DNA) was observed at pH 5, 25 degrees and low ionic strength (mu = .01 M) which was depressed at higher ionic strength and pH. The normalized difference spectrum at mu = .01 M, pH 5 and 25 degrees can be interpreted as indicating an interaction of an exposed guanine residue directly with the enzyme and a coupling of this process with the \"melting\" of short folded segments of d-DNA. The apparent association constant calculated per M guanine residues was 2.4 X 10-4 M-1 under these conditions. The results are discussed in reference to comparable studies on the interaction of RNase T1 with RNA and small guanine ligands.", "contents": "The interaction of ribonuclease T 1 with DNA. The interaction of RNase T1 with calf thymus DNA was studied using uv difference spectroscopy and the effect of the enzyme on DNA melting. There was no indication of RNase T1 binding with native DNA. A prominent difference spectrum for RNase T1 binding with denatured DNA (d-DNA) was observed at pH 5, 25 degrees and low ionic strength (mu = .01 M) which was depressed at higher ionic strength and pH. The normalized difference spectrum at mu = .01 M, pH 5 and 25 degrees can be interpreted as indicating an interaction of an exposed guanine residue directly with the enzyme and a coupling of this process with the \"melting\" of short folded segments of d-DNA. The apparent association constant calculated per M guanine residues was 2.4 X 10-4 M-1 under these conditions. The results are discussed in reference to comparable studies on the interaction of RNase T1 with RNA and small guanine ligands."}
{"id": "PMID:236551", "title": "Studies on human tRNA. I. The rapid, large scale isolation and partial fractionation of placenta and liver tRNA.", "content": "A procedure for the large scale isolation of mammalian tRNA has been applied to the isolation of several grams of human liver, human placenta, rabbit liver and rat liver tRNA. This procedure entails an initial grinding of the tissue in phenol-sodium acetate at acidic pH, followed by DEAE cellulose chromatography. Procedures are also described for analysis of the purified tRNA on the basis of size, using controlled pore glass bean columns. In addition, the acceptor activity of isolated tRNAs has been determined using both the heterologous and homologous synthetases. The chromatographic profile of individual isoaccepting species using BD cellulose chromatography is shown and the 3' terminal nucleoside content was also determined. The methods described now make it feasible for large scale studies of mammalian tRNA enabling us to better understand the relationships between the structure of mammalian tRNA and its many diversified functions.", "contents": "Studies on human tRNA. I. The rapid, large scale isolation and partial fractionation of placenta and liver tRNA. A procedure for the large scale isolation of mammalian tRNA has been applied to the isolation of several grams of human liver, human placenta, rabbit liver and rat liver tRNA. This procedure entails an initial grinding of the tissue in phenol-sodium acetate at acidic pH, followed by DEAE cellulose chromatography. Procedures are also described for analysis of the purified tRNA on the basis of size, using controlled pore glass bean columns. In addition, the acceptor activity of isolated tRNAs has been determined using both the heterologous and homologous synthetases. The chromatographic profile of individual isoaccepting species using BD cellulose chromatography is shown and the 3' terminal nucleoside content was also determined. The methods described now make it feasible for large scale studies of mammalian tRNA enabling us to better understand the relationships between the structure of mammalian tRNA and its many diversified functions."}
{"id": "PMID:236556", "title": "Genetic heterogeneity in familial hypercholesterolemia: evidence for two different mutations affecting functions of low-density lipoprotein receptor.", "content": "Studies in cultured fibroblasts from patients with the clinical syndrome of homozygous familial hypercholesterolemia have disclosed two different mutations affecting the functions of the low density lipoprotein receptor. One of these mutations, described previously, results in a functionless receptor that does not bind low density lipoproteins. In the cells of six patients who appear to be homozygous for this mutant allele, i.e., receptor-negative homozygotes, low density lipoproteins neither suppress hydroxymethylgultaryl-CoA reductase (NADPH) [mevalonate:NADP+ oxidoreductase (CoA-acylating) EC 1.1.1.34] activity nor stimulate cellular cholesterol esterification, even when examined in the presence of concentrations of lipoprotein 500 times higher than those cells. The second type of mutation, described herein, results in a receptor that has a reduced but not absent function. Fibroblasts from three subjects who possess this mutation, i.e., receptor-defective homozygotes, show partial suppression of the same enzyme activity and a detectable increase in cholesterol esterification capacity in the presence of high levels of low density lipoproteins. It was calculated that their degree of function could be achieved if they possessed only about 10% of the normal binding of low density lipoprotein. This level of binding was too low to be reliably detected by the 125-I-labeled low density lipoprotein binding assay. The finding of a second class of mutant cells in which a defect in low density lipoprotein binding is associated with simultaneous defects in both suppression of hydroxymethylglutaryl-CoA reductase activity and stimulation of cholesterol ester formation provides further evidence for the coordinate control of these two processes by the low density lipoprotein receptor.", "contents": "Genetic heterogeneity in familial hypercholesterolemia: evidence for two different mutations affecting functions of low-density lipoprotein receptor. Studies in cultured fibroblasts from patients with the clinical syndrome of homozygous familial hypercholesterolemia have disclosed two different mutations affecting the functions of the low density lipoprotein receptor. One of these mutations, described previously, results in a functionless receptor that does not bind low density lipoproteins. In the cells of six patients who appear to be homozygous for this mutant allele, i.e., receptor-negative homozygotes, low density lipoproteins neither suppress hydroxymethylgultaryl-CoA reductase (NADPH) [mevalonate:NADP+ oxidoreductase (CoA-acylating) EC 1.1.1.34] activity nor stimulate cellular cholesterol esterification, even when examined in the presence of concentrations of lipoprotein 500 times higher than those cells. The second type of mutation, described herein, results in a receptor that has a reduced but not absent function. Fibroblasts from three subjects who possess this mutation, i.e., receptor-defective homozygotes, show partial suppression of the same enzyme activity and a detectable increase in cholesterol esterification capacity in the presence of high levels of low density lipoproteins. It was calculated that their degree of function could be achieved if they possessed only about 10% of the normal binding of low density lipoprotein. This level of binding was too low to be reliably detected by the 125-I-labeled low density lipoprotein binding assay. The finding of a second class of mutant cells in which a defect in low density lipoprotein binding is associated with simultaneous defects in both suppression of hydroxymethylglutaryl-CoA reductase activity and stimulation of cholesterol ester formation provides further evidence for the coordinate control of these two processes by the low density lipoprotein receptor."}
{"id": "PMID:236553", "title": "[Conditions of dextranase formation by Penicillium funiculosum 15].", "content": "The influence of the following factors on the synthesis of extracellular dextranase by Pen. funiculosum 15 has been studied: the quantity and age of the inoculum, pH of the cultivation medium, stimulants of the microbial growth, cultivation temperature and time.  The optimal amount of dextranase has been found to form under the following conditions: inoculum--3 day mycelium constituting 4%, cultivation time--4 to 7 days, temperature--28 to 29 degrees C, initial pH of the medium--6.0.", "contents": "[Conditions of dextranase formation by Penicillium funiculosum 15]. The influence of the following factors on the synthesis of extracellular dextranase by Pen. funiculosum 15 has been studied: the quantity and age of the inoculum, pH of the cultivation medium, stimulants of the microbial growth, cultivation temperature and time.  The optimal amount of dextranase has been found to form under the following conditions: inoculum--3 day mycelium constituting 4%, cultivation time--4 to 7 days, temperature--28 to 29 degrees C, initial pH of the medium--6.0."}
{"id": "PMID:236557", "title": "Protein kinase activation as an early event in the trans-synaptic induction of tyrosine 3-monooxygenase in adrenal medulla.", "content": "An increase of cAMP/cGMP concentration ratio is the earliest stimulus-coupled biochemical change that has been measured in the adrenal medulla during the trans-synaptic induction of tyrosine 3-monooxygenase [EC 1.14.16.2; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating)]. In adrenal medulla of rats receiving reserpine alone (16 mumol/kg intraperitoneally) or reserpine and propranolol (40 mumol/kg intraperitoneally 30 min before reserpine), or exposed to 4 degrees for 4 hr, the extent and duration of the increase of the cAMP/cGMP concentration ratio exceeds the critical value that is required to activate the protein kinases (EC 2.7.1.37; ATP:protein phosphotransferase). Gel filtration experiments indicate that during this activation, the catalytic subunit of the protein kinase (low-molecular-weight enzyme) is released from the holoenzyme. The activation of protein kinase lasts longer than the increase in the cAMP/cGMP concentration ratio and appears to be an obligatory early event that mediates the increase of tyrosine monooxygenase synthesis. The trans-synaptic induction of the monooxygenase in adrenal medulla appears to be due to an increased synthesis of the enzyme;the rate for monooxygenase degradation is proportional to the number of enzyme molecules that are present at various stages of the induction process.", "contents": "Protein kinase activation as an early event in the trans-synaptic induction of tyrosine 3-monooxygenase in adrenal medulla. An increase of cAMP/cGMP concentration ratio is the earliest stimulus-coupled biochemical change that has been measured in the adrenal medulla during the trans-synaptic induction of tyrosine 3-monooxygenase [EC 1.14.16.2; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating)]. In adrenal medulla of rats receiving reserpine alone (16 mumol/kg intraperitoneally) or reserpine and propranolol (40 mumol/kg intraperitoneally 30 min before reserpine), or exposed to 4 degrees for 4 hr, the extent and duration of the increase of the cAMP/cGMP concentration ratio exceeds the critical value that is required to activate the protein kinases (EC 2.7.1.37; ATP:protein phosphotransferase). Gel filtration experiments indicate that during this activation, the catalytic subunit of the protein kinase (low-molecular-weight enzyme) is released from the holoenzyme. The activation of protein kinase lasts longer than the increase in the cAMP/cGMP concentration ratio and appears to be an obligatory early event that mediates the increase of tyrosine monooxygenase synthesis. The trans-synaptic induction of the monooxygenase in adrenal medulla appears to be due to an increased synthesis of the enzyme;the rate for monooxygenase degradation is proportional to the number of enzyme molecules that are present at various stages of the induction process."}
{"id": "PMID:236554", "title": "[Specificity of the degradation and synthesis of dinucleoside monophosphates by RNAase C2 of Asp. clavatus].", "content": "The ability of RNAase E2 to degradate dinucleoside moniphosphates and to form internucleotide bonds was studied. The compounds of the GpN type were found to be a good substrate for RNase C2. The pH optimum for GpC was 5.5 (acetate buffer) and the temperature optimum was 30 degrees C. The values of Km and Vmax on GpC, GpA, GpG and GpU were determined. The affinity of the substrates for the enzyme decreased in the sequence GpC greater than GpG greater than GpA GREATER THAN GpU. RNase C2 catalyze the synthesis of GpC and GpU. The yield of GpC amounted to 60% and that of GpU was 35%. These data indicate that RNase C2 FROM Asp. clavatum is guanyl ribonuclease (EC 3.1.4.8.).", "contents": "[Specificity of the degradation and synthesis of dinucleoside monophosphates by RNAase C2 of Asp. clavatus]. The ability of RNAase E2 to degradate dinucleoside moniphosphates and to form internucleotide bonds was studied. The compounds of the GpN type were found to be a good substrate for RNase C2. The pH optimum for GpC was 5.5 (acetate buffer) and the temperature optimum was 30 degrees C. The values of Km and Vmax on GpC, GpA, GpG and GpU were determined. The affinity of the substrates for the enzyme decreased in the sequence GpC greater than GpG greater than GpA GREATER THAN GpU. RNase C2 catalyze the synthesis of GpC and GpU. The yield of GpC amounted to 60% and that of GpU was 35%. These data indicate that RNase C2 FROM Asp. clavatum is guanyl ribonuclease (EC 3.1.4.8.)."}
{"id": "PMID:236555", "title": "[Respiratory-renal regulation of acid-base equilibrium disorders in patients with diabetes mellitus].", "content": "The effects of ration on postprandial serum glucose and insulin were determined in 12 lactating Holstein cows. Six were fed a high grain ration of 15% hay and 85% concentrate (dry basis) and the other six a control ration of 55% corn silage, 10% hay, and 35% concentrate. High grain feeding increased flucose and insulin at all hours postfeeding as compared to control cows. In the cows fed high grain, glucose increased from 63.3 to 72.2 mg/100 ml and insulin from 19.2 to 25.6 muunits/ml serum just before feeding to 3 h postfeeding. Values for 2, 3, and 4 h samples were greater than for other sampling times. Serum glucose was 55.5 mg/100 ml at 1 h in control cows which was above other samples. Serum insulin followed a pattern similar to glucose in controls but was not significantly different with time. The blood changes due to high grain feeding are probably related to low milk fat production.", "contents": "[Respiratory-renal regulation of acid-base equilibrium disorders in patients with diabetes mellitus]. The effects of ration on postprandial serum glucose and insulin were determined in 12 lactating Holstein cows. Six were fed a high grain ration of 15% hay and 85% concentrate (dry basis) and the other six a control ration of 55% corn silage, 10% hay, and 35% concentrate. High grain feeding increased flucose and insulin at all hours postfeeding as compared to control cows. In the cows fed high grain, glucose increased from 63.3 to 72.2 mg/100 ml and insulin from 19.2 to 25.6 muunits/ml serum just before feeding to 3 h postfeeding. Values for 2, 3, and 4 h samples were greater than for other sampling times. Serum glucose was 55.5 mg/100 ml at 1 h in control cows which was above other samples. Serum insulin followed a pattern similar to glucose in controls but was not significantly different with time. The blood changes due to high grain feeding are probably related to low milk fat production."}
{"id": "PMID:236558", "title": "Activation by cyclic 3':5'-adenosine monophosphate of tyrosine hydroxylase in the rat brain.", "content": "Membrane-permeable derivatives of cyclic AMP (cAMP) produced concentration-dependent increases in activity of tyrosine hydroxylase (L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2) in membrane-limited nerve endings (synaptosomes) prepared from three regions of rat brain. Increased hydroxylation occurred even after preincubation and removal of dibutyryl cyclic AMP. In all brain regions, the hydroxylation of phenylalanine and tyrosine was increased, but dibutyryl cAMP had little effect on activity of tryptophan hydroxylase, no effect on aromatic amino-acid decarboxylase, on uptake of tyrosine or phenylalanine, uptake or efflux of dopamine, or distribution of hydroxylase between cytoplasmic and particulate components of the synaptosomes. Dibutyryl cAMP decreased inhibition of catecholamine synthesis in synaptosomes by dopamine and apomorphine. In a soluble preparation of striatal tyrosine hydroxylase, activity was increased by addition of lower concentrations of cAMP or dibutyryl cAMP than with unbroken nerve endings, when subsaturating concentrations of tyrosine and cofactor were employed, while butyrate, chloride, 5'-AMP, ADP, ATP, and cyclic GMP had no activating effect. Increased activity of soluble tyrosine hydroxylase was reflected in increased affinity (Km) for substrate and cofactor and decreased affinity (Ki) for inhibitory end-product (dopamine), suggesting a change in the physical-chemical state of the enzyme or an activator molecule. Cyclic AMP may activate tyrosine hydroxylase during periods of increased neuronal activity.", "contents": "Activation by cyclic 3':5'-adenosine monophosphate of tyrosine hydroxylase in the rat brain. Membrane-permeable derivatives of cyclic AMP (cAMP) produced concentration-dependent increases in activity of tyrosine hydroxylase (L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2) in membrane-limited nerve endings (synaptosomes) prepared from three regions of rat brain. Increased hydroxylation occurred even after preincubation and removal of dibutyryl cyclic AMP. In all brain regions, the hydroxylation of phenylalanine and tyrosine was increased, but dibutyryl cAMP had little effect on activity of tryptophan hydroxylase, no effect on aromatic amino-acid decarboxylase, on uptake of tyrosine or phenylalanine, uptake or efflux of dopamine, or distribution of hydroxylase between cytoplasmic and particulate components of the synaptosomes. Dibutyryl cAMP decreased inhibition of catecholamine synthesis in synaptosomes by dopamine and apomorphine. In a soluble preparation of striatal tyrosine hydroxylase, activity was increased by addition of lower concentrations of cAMP or dibutyryl cAMP than with unbroken nerve endings, when subsaturating concentrations of tyrosine and cofactor were employed, while butyrate, chloride, 5'-AMP, ADP, ATP, and cyclic GMP had no activating effect. Increased activity of soluble tyrosine hydroxylase was reflected in increased affinity (Km) for substrate and cofactor and decreased affinity (Ki) for inhibitory end-product (dopamine), suggesting a change in the physical-chemical state of the enzyme or an activator molecule. Cyclic AMP may activate tyrosine hydroxylase during periods of increased neuronal activity."}
{"id": "PMID:236559", "title": "Adenine formation from adenosine by mycoplasmas: adenosine phosphorylase activity.", "content": "Mammalian cells have enzymes to convert adenosine to inosine by deamination and inosine to hypoxanthine by phosphorolysis, but they do not possess the enzymes necessary to form the free base, adenine, from adenosine. Mycoplasmas grown in broth or in cell cultures can produce adenine from adenosine. This activity was detected in a variety of mycoplasmatales, and the enzyme was shown to be adenosine phosphorylase. Adenosine formation from adenine and ribose 1-phosphate, the reverse reaction of adenine formation from adenosine, was also observed with the mycoplasma enzyme. Adenosine phosphorylase is apparently common to the mycoplasmatales but it is not universal, and the organisms can be divided into three groups on the basis of their use of adenosine as substrate. Thirteen of 16 Mycoplasma, Acholeplasma, and Siroplasma species tested exhibit adenosine phosphorylase activity. M. lipophilium differed from the other mycoplasmas and shared with mammalian cells the ability to convert adenosine to inosine by deamination. M. pneumoniae and the unclassified M. sp. 70-159 showed no reaction with adenosine. Adenosine phosphorylase activity offers an additional method for the detection of mycoplasma contamination of cells. The patterns of nucleoside metabolism will provide additional characteristics for identification of mycoplasmas and also may provide new insight into the classification of mycoplasmas.", "contents": "Adenine formation from adenosine by mycoplasmas: adenosine phosphorylase activity. Mammalian cells have enzymes to convert adenosine to inosine by deamination and inosine to hypoxanthine by phosphorolysis, but they do not possess the enzymes necessary to form the free base, adenine, from adenosine. Mycoplasmas grown in broth or in cell cultures can produce adenine from adenosine. This activity was detected in a variety of mycoplasmatales, and the enzyme was shown to be adenosine phosphorylase. Adenosine formation from adenine and ribose 1-phosphate, the reverse reaction of adenine formation from adenosine, was also observed with the mycoplasma enzyme. Adenosine phosphorylase is apparently common to the mycoplasmatales but it is not universal, and the organisms can be divided into three groups on the basis of their use of adenosine as substrate. Thirteen of 16 Mycoplasma, Acholeplasma, and Siroplasma species tested exhibit adenosine phosphorylase activity. M. lipophilium differed from the other mycoplasmas and shared with mammalian cells the ability to convert adenosine to inosine by deamination. M. pneumoniae and the unclassified M. sp. 70-159 showed no reaction with adenosine. Adenosine phosphorylase activity offers an additional method for the detection of mycoplasma contamination of cells. The patterns of nucleoside metabolism will provide additional characteristics for identification of mycoplasmas and also may provide new insight into the classification of mycoplasmas."}
{"id": "PMID:236560", "title": "Circadian rhythm of tyrosine hydroxylase induction by short-term cold stress: modulatory action of glucocorticoids in newborn and adult rats.", "content": "The trans-synaptic induction of tyrosine hydroxylase [tyrosine 3-monooxygenase; EC 1.14.16.2, L-tyrosine, tetrahydropteridine: oxygen oxidoreductase (3-hydroxylating)] in adrenal medulla and sympathetic ganglia by short-term (1-2 hr) cold stress (4 degrees) exhibits a circadian rhythm which seems to be causally related to the diurnal changes in adrenal glucocorticoid synthesis. In induction is maximal during the morning hours, when plasma corticoid concentrations (reflecting corticoid synthesis in the adrenal cortex) are minimal. In contrast, initiation of tyrosine hydroxylase induction in sympathetic ganglia is only possible in the afternoon. These observations suggest that tyrosine hydroxylase inducibility in the adrenal medulla is optimal during periods of low corticoid synthesis (the adrenal medulla is exposed to excessively high corticoid concentrations directly originating from the adjacent cortex), whereas in sympathetic ganglia an induction is only possible during the period of high plasma corticoid concentrations. This assumption is supported by the observation that in the first postnatal weeks, when the pituitary--adrenocortical system is not yet operating and plasma corticoid concentrations are low, initiation of tyrosine hydroxylase induction in the adrenal medulla is possible at any time of the day, whereas in sympathetic ganglia it is not possible at all. However, after administration of glycocorticoids initiation of tyrosine hydroxylase induction by short-term cold stress is also possible in newborn animals and in adults during the morning hours. The importance of glucocorticoids as modulators for the initiation of trans-synaptic tyrosine hydroxylase induction can also be deduced from the observation that in sympathetic ganglia kept in organ cultures and induction of the hydroxylase by cholinomimetics is only possible when glycocorticoids are added to the culture medium.", "contents": "Circadian rhythm of tyrosine hydroxylase induction by short-term cold stress: modulatory action of glucocorticoids in newborn and adult rats. The trans-synaptic induction of tyrosine hydroxylase [tyrosine 3-monooxygenase; EC 1.14.16.2, L-tyrosine, tetrahydropteridine: oxygen oxidoreductase (3-hydroxylating)] in adrenal medulla and sympathetic ganglia by short-term (1-2 hr) cold stress (4 degrees) exhibits a circadian rhythm which seems to be causally related to the diurnal changes in adrenal glucocorticoid synthesis. In induction is maximal during the morning hours, when plasma corticoid concentrations (reflecting corticoid synthesis in the adrenal cortex) are minimal. In contrast, initiation of tyrosine hydroxylase induction in sympathetic ganglia is only possible in the afternoon. These observations suggest that tyrosine hydroxylase inducibility in the adrenal medulla is optimal during periods of low corticoid synthesis (the adrenal medulla is exposed to excessively high corticoid concentrations directly originating from the adjacent cortex), whereas in sympathetic ganglia an induction is only possible during the period of high plasma corticoid concentrations. This assumption is supported by the observation that in the first postnatal weeks, when the pituitary--adrenocortical system is not yet operating and plasma corticoid concentrations are low, initiation of tyrosine hydroxylase induction in the adrenal medulla is possible at any time of the day, whereas in sympathetic ganglia it is not possible at all. However, after administration of glycocorticoids initiation of tyrosine hydroxylase induction by short-term cold stress is also possible in newborn animals and in adults during the morning hours. The importance of glucocorticoids as modulators for the initiation of trans-synaptic tyrosine hydroxylase induction can also be deduced from the observation that in sympathetic ganglia kept in organ cultures and induction of the hydroxylase by cholinomimetics is only possible when glycocorticoids are added to the culture medium."}
{"id": "PMID:236561", "title": "Chemical nature of bioluminescence systems in coelenterates.", "content": "Analysis of substances involved in light-emitting reactions among bioluminescent coelenterates has revealed a pronounced uniformity in the structural features of initial reactants, i.e., \"luciferins\" and photo-protein chromophores, as well as the light-emitter product. This product is structurally identical among the different classes of coelenterates: Hydrozoa (the jellyfish, Aequorea), Anthozoa (the sea cactus, Cavernularia; sea pansy, Renilla; and sea pen, Leioptilus), and very likely also the Scyphozoa (the jellyfish, Pelagia). In each of these instances the reaction product, namely, 2-(p-hydroxy-pnenylacetyl)amino-3-benzyl-5-(p-hydroxyphenyl) pyrazine, is the actual light-emitter, whether it occurs in a Ca2+-triggered photoprotein type of luminescence, or in a \"luciferin-luciferase\" type. The evidence indicates that in certain coelenterates, e.g., Cavernularia, these two types are equally significant, whereas in others (Renilla and Leioptilus) the \"luciferin-luciferase\" type predominates over the Ca-triggerable photoprotein type, and finally that only the photoprotein type functions in the luciferaseless jellyfish, Aequorea. In all instances investigated, the structure of the light-emitter prior to the luminescence reaction appears to be essentially the same as that of the chromophore of unreacted aequorin. The product of the luminescence reaction is absent in extracts of non luminous species. However, a product very similar to that of luminescent coelenterates occurs also in representatives of other phyla, including the cephalopod molluscs, e.g., the \"firefly squid\" Watasenia and probably various ctenophores as well.", "contents": "Chemical nature of bioluminescence systems in coelenterates. Analysis of substances involved in light-emitting reactions among bioluminescent coelenterates has revealed a pronounced uniformity in the structural features of initial reactants, i.e., \"luciferins\" and photo-protein chromophores, as well as the light-emitter product. This product is structurally identical among the different classes of coelenterates: Hydrozoa (the jellyfish, Aequorea), Anthozoa (the sea cactus, Cavernularia; sea pansy, Renilla; and sea pen, Leioptilus), and very likely also the Scyphozoa (the jellyfish, Pelagia). In each of these instances the reaction product, namely, 2-(p-hydroxy-pnenylacetyl)amino-3-benzyl-5-(p-hydroxyphenyl) pyrazine, is the actual light-emitter, whether it occurs in a Ca2+-triggered photoprotein type of luminescence, or in a \"luciferin-luciferase\" type. The evidence indicates that in certain coelenterates, e.g., Cavernularia, these two types are equally significant, whereas in others (Renilla and Leioptilus) the \"luciferin-luciferase\" type predominates over the Ca-triggerable photoprotein type, and finally that only the photoprotein type functions in the luciferaseless jellyfish, Aequorea. In all instances investigated, the structure of the light-emitter prior to the luminescence reaction appears to be essentially the same as that of the chromophore of unreacted aequorin. The product of the luminescence reaction is absent in extracts of non luminous species. However, a product very similar to that of luminescent coelenterates occurs also in representatives of other phyla, including the cephalopod molluscs, e.g., the \"firefly squid\" Watasenia and probably various ctenophores as well."}
{"id": "PMID:236562", "title": "Interaction of glyoxal and methylglyoxal with biogenic amines.", "content": "Glyoxal and methylglyoxal interact with biogenic amines and form biologically active free radicals. Electron spin resonance absorption of the radical at room temperature is characterized by a signal at g equals 2.004 with peak-to-peak width of 29 G. An optical absorption at 400 nm with molar absorptivity of 23,000 accompanies the formation of the radical. The dry powdered preparation of the same reaction, which is considered to be the seconardy product, gives an electron spin resonance signal much narrower and 1/200 in intensity compared with the one in solution. Similarly the 400 nm absorption intensity is 1/8 that of the primary product. Possible biological significance of the primary and the secondary product, in relation to muscular dystrophy and photophosphorylation, is discussed.", "contents": "Interaction of glyoxal and methylglyoxal with biogenic amines. Glyoxal and methylglyoxal interact with biogenic amines and form biologically active free radicals. Electron spin resonance absorption of the radical at room temperature is characterized by a signal at g equals 2.004 with peak-to-peak width of 29 G. An optical absorption at 400 nm with molar absorptivity of 23,000 accompanies the formation of the radical. The dry powdered preparation of the same reaction, which is considered to be the seconardy product, gives an electron spin resonance signal much narrower and 1/200 in intensity compared with the one in solution. Similarly the 400 nm absorption intensity is 1/8 that of the primary product. Possible biological significance of the primary and the secondary product, in relation to muscular dystrophy and photophosphorylation, is discussed."}
{"id": "PMID:236564", "title": "A Quantitative study of histamine H2-receptor bockade by burimamide in isolated artica.", "content": "The onset of burimamide inhibition of histamine stimulation of rabbit atria is rapid, and a near steady-state blockade occurs at approximately 15 min ( larger than or equal to 90% complete). The blockade is reversible but requires several washings suggesting the disassociation is slow. The administration of histamine may accelerate the decay of the burimamide effect. Reciprocal plots (rate response versus histamine concentration) of dose-response curves are linear for both rabbit and guinea pig atria. In the presence of low concentrations of burimamide; (2.4  times 10-5 M), the displacement of curves suggests a competitive type of inhibition both for rabbit and guinea guinea pig atria. The apparent association constants calculated from these curves are: K1 (rabbit) 3.7 times 10-6M and K-1 (guinea pig) 6.7 times 10-6M. These results for guinea pig atria are in satisfactory agreement with the value obtained in another laboratory (2). At higher concentrations of burimamide, inhibition curves showed distinct evidence of departure from competitive character for both guinea pig and rabbit atria.", "contents": "A Quantitative study of histamine H2-receptor bockade by burimamide in isolated artica. The onset of burimamide inhibition of histamine stimulation of rabbit atria is rapid, and a near steady-state blockade occurs at approximately 15 min ( larger than or equal to 90% complete). The blockade is reversible but requires several washings suggesting the disassociation is slow. The administration of histamine may accelerate the decay of the burimamide effect. Reciprocal plots (rate response versus histamine concentration) of dose-response curves are linear for both rabbit and guinea pig atria. In the presence of low concentrations of burimamide; (2.4  times 10-5 M), the displacement of curves suggests a competitive type of inhibition both for rabbit and guinea guinea pig atria. The apparent association constants calculated from these curves are: K1 (rabbit) 3.7 times 10-6M and K-1 (guinea pig) 6.7 times 10-6M. These results for guinea pig atria are in satisfactory agreement with the value obtained in another laboratory (2). At higher concentrations of burimamide, inhibition curves showed distinct evidence of departure from competitive character for both guinea pig and rabbit atria."}
{"id": "PMID:236565", "title": "Serum antitrypsin synthesis by the isolated perfused rat liver.", "content": "The isolated perfused rat liver synthesizes antitrypsin activity in a linear fashion as long as 24 hr. The rate of synthesis may be ten times the rate necessary for physiologic levels in vivo. These data are compatible with the liver as the principal site of synthesis of serum antitryptic activity in the rat. The antitrypsin activity of the rat perfusate resembles that of normal human plasma in liability to heat (56 degrees) and to acid (below pH 6) and in apparent molecular size (elution from Sephadex G-200).", "contents": "Serum antitrypsin synthesis by the isolated perfused rat liver. The isolated perfused rat liver synthesizes antitrypsin activity in a linear fashion as long as 24 hr. The rate of synthesis may be ten times the rate necessary for physiologic levels in vivo. These data are compatible with the liver as the principal site of synthesis of serum antitryptic activity in the rat. The antitrypsin activity of the rat perfusate resembles that of normal human plasma in liability to heat (56 degrees) and to acid (below pH 6) and in apparent molecular size (elution from Sephadex G-200)."}
{"id": "PMID:236566", "title": "Complement in graft versus host disease: IL Depletion of complement components during a systemic graft versus host reaction in the rat (38499).", "content": "Serum complement (C) and C components were examined during a systemic graft versus host (GVH) reaction in the rat. In our series of experiments (Lewis times Brown Norway) F-1 hybrid rats (60-80g) were given 200 times 10-6 or 400 times 10-6 Lewis spleen cells intravenously. Clinical GVH disease appeared 5-7 days after cell injection. Five of six rats in the experimental groups had a fall in levels of serum C2 (20-76%) and C4 (75-98%). Only one of six rats in the control group had a significant fall in C components. In a subsequent experiment (Fisher 344 times Brown Norway) F-1hybrid rats (60g) were given 400 times 10-6 Fischer 344 spleen cells or 200 times 10-6 Fischer  344 Ficoll-Hypaque separated spleen lymphocytes. Clincal  GVH disease in this instance appeared on day 10. As in the previous experiments C2 and C4 fell markedly, 20-60% and 60-8-%, respectively, from baseline titers. The control groups did not have a significant fall in C2 or C4. Further examination showed reduction in C3, C5, C6,AND C8 suggesting a sequential activation of the C system via the classical pathway. We have postulated that the cells undergoing blast transformation may be activating the C system through membrane changes during the GVH reaction. Furthermore, the deficiency of C AND C components during GVH disease may contribute to the increased susceptibility of the host to infection and sepsis.", "contents": "Complement in graft versus host disease: IL Depletion of complement components during a systemic graft versus host reaction in the rat (38499). Serum complement (C) and C components were examined during a systemic graft versus host (GVH) reaction in the rat. In our series of experiments (Lewis times Brown Norway) F-1 hybrid rats (60-80g) were given 200 times 10-6 or 400 times 10-6 Lewis spleen cells intravenously. Clinical GVH disease appeared 5-7 days after cell injection. Five of six rats in the experimental groups had a fall in levels of serum C2 (20-76%) and C4 (75-98%). Only one of six rats in the control group had a significant fall in C components. In a subsequent experiment (Fisher 344 times Brown Norway) F-1hybrid rats (60g) were given 400 times 10-6 Fischer 344 spleen cells or 200 times 10-6 Fischer  344 Ficoll-Hypaque separated spleen lymphocytes. Clincal  GVH disease in this instance appeared on day 10. As in the previous experiments C2 and C4 fell markedly, 20-60% and 60-8-%, respectively, from baseline titers. The control groups did not have a significant fall in C2 or C4. Further examination showed reduction in C3, C5, C6,AND C8 suggesting a sequential activation of the C system via the classical pathway. We have postulated that the cells undergoing blast transformation may be activating the C system through membrane changes during the GVH reaction. Furthermore, the deficiency of C AND C components during GVH disease may contribute to the increased susceptibility of the host to infection and sepsis."}
{"id": "PMID:236567", "title": "Inhibition of Hageman factor, plasma thromboplastin antecedent, thrombin and other clotting factors by phenylglyoxal hydrate (38500).", "content": "Exposure of purified Hageman factor (HF, Factor XII) to phenylglyoxal hydrate (PHG), an agent reacting with arginine residues in protein, inhibited its coagulant properties upon subsequent exposure of negatively charged agents. Once HF had been exposed to kaolin or ellagic acid, however, subsequent addition of PHG was much less inhibitory. PHG had no effect upon the ability of HF to bind to negatively charged surfaces. PGH also inhibited preparations of activated PTA (Factor XI) and thrombin, and, when incubated with plasma, reduced the titer of coagulable fibrinogen, PTA Christmas factor (Factor IX), antihemophilic factor (Factor VIII), Factor VII, Stuart factor (Factor X), proaccelerin (Factor V) and prothrombin (Factor II), and to a lesser degres, HF.", "contents": "Inhibition of Hageman factor, plasma thromboplastin antecedent, thrombin and other clotting factors by phenylglyoxal hydrate (38500). Exposure of purified Hageman factor (HF, Factor XII) to phenylglyoxal hydrate (PHG), an agent reacting with arginine residues in protein, inhibited its coagulant properties upon subsequent exposure of negatively charged agents. Once HF had been exposed to kaolin or ellagic acid, however, subsequent addition of PHG was much less inhibitory. PHG had no effect upon the ability of HF to bind to negatively charged surfaces. PGH also inhibited preparations of activated PTA (Factor XI) and thrombin, and, when incubated with plasma, reduced the titer of coagulable fibrinogen, PTA Christmas factor (Factor IX), antihemophilic factor (Factor VIII), Factor VII, Stuart factor (Factor X), proaccelerin (Factor V) and prothrombin (Factor II), and to a lesser degres, HF."}
{"id": "PMID:236568", "title": "Response of muscular and cutaneous vessels to physiologic stimulation of chemoreceptors (38505).", "content": "Experiments were performed to determine whether physiologic stimulation of carotid chemoreceptors produces different responses in blood vessels of skin and muscle. Carotid chemoreceptors of anesthetized dogs were stimulated with hypoxic and hypercapnic blood and responses were observed in the isolated, perfused gracilis muscle and hindpaw. Chemoreceptor stimulation produced vasoconstriction in the muscle and vadodilatation in the paw (a predominantly cutaneous vascular bed). Responses to hypoxia without hypercapnic acidosis tended to be less pronounced. The study indicates that physiologic stimulation of carotid chemoreceptors produces contrasting responses in different vascular beds.", "contents": "Response of muscular and cutaneous vessels to physiologic stimulation of chemoreceptors (38505). Experiments were performed to determine whether physiologic stimulation of carotid chemoreceptors produces different responses in blood vessels of skin and muscle. Carotid chemoreceptors of anesthetized dogs were stimulated with hypoxic and hypercapnic blood and responses were observed in the isolated, perfused gracilis muscle and hindpaw. Chemoreceptor stimulation produced vasoconstriction in the muscle and vadodilatation in the paw (a predominantly cutaneous vascular bed). Responses to hypoxia without hypercapnic acidosis tended to be less pronounced. The study indicates that physiologic stimulation of carotid chemoreceptors produces contrasting responses in different vascular beds."}
{"id": "PMID:236569", "title": "Effect of severe anoxia on the permeability of gastric mucosa (38517).", "content": "The effect of severe anoxia produced by gassing with 100% nitrogen on gastric mucosal permeability and hydrogen ion back diffusion was investigated using an in vitro preparation of rabbit fundic gastric mucosa mounted in an Ussing chamber. Permeability was estimated by determination of the flux of the water soluble, nonlipidsoluble molecule erythritol from the mucosal to serosal solution. The flux rate across normal tissue was 2.80 plus or minus 0.41 pmoles/cm-2/sec, and rose to 3.32 plus or minus 0.57 pmoles/cm-2/sec after 2 hr of severe anoxia. Hydrogen ion ack diffusion was measured by determining with a pH stat the amount of hydrogen required to maintain the [H+] of the mucosal solution at 0.1, 1.0, 2.0 and 3.2 mEq/L in both normal and anoxic tissues. One hour of anoxia increased the back diffusion of H+, but the changes only became statistically significant at all pH values after 1.5 hr. Anoxia did however cause an immediate fall in potential difference to zero, and a rise in resistance which after 30 min fell progressively to preanoxic levels. Anoxia produces a small increase in gastric mucosal, permeability, an effect which may be enhanced by other factors.", "contents": "Effect of severe anoxia on the permeability of gastric mucosa (38517). The effect of severe anoxia produced by gassing with 100% nitrogen on gastric mucosal permeability and hydrogen ion back diffusion was investigated using an in vitro preparation of rabbit fundic gastric mucosa mounted in an Ussing chamber. Permeability was estimated by determination of the flux of the water soluble, nonlipidsoluble molecule erythritol from the mucosal to serosal solution. The flux rate across normal tissue was 2.80 plus or minus 0.41 pmoles/cm-2/sec, and rose to 3.32 plus or minus 0.57 pmoles/cm-2/sec after 2 hr of severe anoxia. Hydrogen ion ack diffusion was measured by determining with a pH stat the amount of hydrogen required to maintain the [H+] of the mucosal solution at 0.1, 1.0, 2.0 and 3.2 mEq/L in both normal and anoxic tissues. One hour of anoxia increased the back diffusion of H+, but the changes only became statistically significant at all pH values after 1.5 hr. Anoxia did however cause an immediate fall in potential difference to zero, and a rise in resistance which after 30 min fell progressively to preanoxic levels. Anoxia produces a small increase in gastric mucosal, permeability, an effect which may be enhanced by other factors."}
{"id": "PMID:236570", "title": "Role of vasoactive substances in active hyperemia in skeletal muscle (38520).", "content": "A prolonged, 2-hr period of exercise hyperemia in the canine gracilis muscle was associated with initial increases in the arteriovenous differences for potassium, hydrogen and osmolality. However, that for hydrogen decreased and those for potassium and osmolality became negligible by the 120th min while blood flow remained elevated. Thus, potassium and osmolality do not appear to participate importantly in the maintenance of exercise hyperemia in canine gracilis muscle. A bioassay muscle did not respond with comparable dilation when submaximal, graded levels of exercise hyperemia were induced in an upstream, donor muscle but did respond more comparably in terms of magnitude and time course when the exercise was more severe. Thus, stable vasoactive substances may not entirely account for exercise hyperemia and the study fails to provide evidence that the capillary acts as a significant barrier to the vasoactive substances.", "contents": "Role of vasoactive substances in active hyperemia in skeletal muscle (38520). A prolonged, 2-hr period of exercise hyperemia in the canine gracilis muscle was associated with initial increases in the arteriovenous differences for potassium, hydrogen and osmolality. However, that for hydrogen decreased and those for potassium and osmolality became negligible by the 120th min while blood flow remained elevated. Thus, potassium and osmolality do not appear to participate importantly in the maintenance of exercise hyperemia in canine gracilis muscle. A bioassay muscle did not respond with comparable dilation when submaximal, graded levels of exercise hyperemia were induced in an upstream, donor muscle but did respond more comparably in terms of magnitude and time course when the exercise was more severe. Thus, stable vasoactive substances may not entirely account for exercise hyperemia and the study fails to provide evidence that the capillary acts as a significant barrier to the vasoactive substances."}
{"id": "PMID:236573", "title": "Metabolism of octanoate and its effect on glucose and palmitate utilization by isolated fat cells.", "content": "Octanoate is avidly incorporated into triglycerides by isolated rat adipocytes in the presence of glucose via direct esterification without prior beta-oxidation to acetyl CoA.  This was shown by separation of the products formed from (1-14C) octanoate into lipid classes using Florisil columns, and after alkaline hydrolysis of the triglyceride fraction, by cochromatogrpahy with authentic fatty acids on reverse-phase Celite columns. The relative contribution of (U-14C) glucose and (1-14C) octanoate to triglyceride synthesis and CO2 formation were studied under a variety of conditions.  Concentrations of octanoate below 0.5 mM have a stimulatory effect on the conversion of (U-14C) glucose to CO2, triglycerides and esterified fatty acids.  However, a marked depression of fatty acid synthesis from (U-14C) glucose was observed in the presence of millimolar concentrations of octanoate.  Octanoate had no effect on the esterification of palmitate, but palmitate strongly depressed the ability of rat adipocytes to esterify octanoate.", "contents": "Metabolism of octanoate and its effect on glucose and palmitate utilization by isolated fat cells. Octanoate is avidly incorporated into triglycerides by isolated rat adipocytes in the presence of glucose via direct esterification without prior beta-oxidation to acetyl CoA.  This was shown by separation of the products formed from (1-14C) octanoate into lipid classes using Florisil columns, and after alkaline hydrolysis of the triglyceride fraction, by cochromatogrpahy with authentic fatty acids on reverse-phase Celite columns. The relative contribution of (U-14C) glucose and (1-14C) octanoate to triglyceride synthesis and CO2 formation were studied under a variety of conditions.  Concentrations of octanoate below 0.5 mM have a stimulatory effect on the conversion of (U-14C) glucose to CO2, triglycerides and esterified fatty acids.  However, a marked depression of fatty acid synthesis from (U-14C) glucose was observed in the presence of millimolar concentrations of octanoate.  Octanoate had no effect on the esterification of palmitate, but palmitate strongly depressed the ability of rat adipocytes to esterify octanoate."}
{"id": "PMID:236574", "title": "Evidence for beneficial effect of intravenous glucose on the hemodynamic response to acute asphyxia.", "content": "Anesthetized rabbits were subjected to two 4-min periods of asphyxia with a 15-min recovery period intervening. During the recovery period animals received an iv infusion of either isotonic glucose or mannitol. Results indicated that glucose had a beneficial effect on systolic blood pressure during the second period of asphyxia. A direct metabolic action of glucose on the myocardium is favored as the explanation, but other possibilities include peripheral or neurohumoral effects.", "contents": "Evidence for beneficial effect of intravenous glucose on the hemodynamic response to acute asphyxia. Anesthetized rabbits were subjected to two 4-min periods of asphyxia with a 15-min recovery period intervening. During the recovery period animals received an iv infusion of either isotonic glucose or mannitol. Results indicated that glucose had a beneficial effect on systolic blood pressure during the second period of asphyxia. A direct metabolic action of glucose on the myocardium is favored as the explanation, but other possibilities include peripheral or neurohumoral effects."}
{"id": "PMID:236575", "title": "Lipoprotein lipase activity in bovine aorta.", "content": "A lipoprotein lipase in the bovine arterial wall has been identified and partially characterized. The enzyme has a Km apparent of 1 mM for triolein in a phosphatidylcholine stabilized emulsion. The lipase was stimulated 20- to 30-fold by the addition of heated rat plasma to the assay medium. The activity exhibited a pH optimum at 8.6. Protamine sulfate (1.0 mg/ml) inhibited the activity by 50%, whereas 1.4 M sodium chloride inhibited by 85%. Sodium fluoride, an inhibitor of the hormone-sensitive lipase, had no effect on the activity. Additions of low concentrations of heparin or Ca-2+ to the enzyme caused a slight stimulation of the lipolytic activity. A crude sectioning of the aorta revealed specific activity of lipoprotein lipase to be highest at the endothelial side of the artery.", "contents": "Lipoprotein lipase activity in bovine aorta. A lipoprotein lipase in the bovine arterial wall has been identified and partially characterized. The enzyme has a Km apparent of 1 mM for triolein in a phosphatidylcholine stabilized emulsion. The lipase was stimulated 20- to 30-fold by the addition of heated rat plasma to the assay medium. The activity exhibited a pH optimum at 8.6. Protamine sulfate (1.0 mg/ml) inhibited the activity by 50%, whereas 1.4 M sodium chloride inhibited by 85%. Sodium fluoride, an inhibitor of the hormone-sensitive lipase, had no effect on the activity. Additions of low concentrations of heparin or Ca-2+ to the enzyme caused a slight stimulation of the lipolytic activity. A crude sectioning of the aorta revealed specific activity of lipoprotein lipase to be highest at the endothelial side of the artery."}
{"id": "PMID:236576", "title": "Effect of exercise on response of liver lipogenic enzymes to a high fructose diet.", "content": "Meal-fed Long-Evans rats fed a high fructose diet and exercised for 2-hr daily on a treadmill for three days had lower levels of several hepatic lipogenic enzymes (acetyl CoA carboxylase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, malic enzyme and citrate cleavage enzyme) than did sedentary rats pair-fed the diet. Accumulation of triglycerides in plasma following ingestion of a fat-free, high fructose meal and injection of Triton WR-1339, an inhibitor of plasma triglyceride clearance, was not significantly different in the two groups of animals. All of the hepatic lipogenic enzymes measured, with the exception of citrate cleavage enzyme, attained similar levels in the runners as in the controls after 5 days on the high fructose diet. Thus the exercise appeared to affect the time course of the increase in the levels of activity of most of the lipogenic enzymes but not the final steady state levels attained.", "contents": "Effect of exercise on response of liver lipogenic enzymes to a high fructose diet. Meal-fed Long-Evans rats fed a high fructose diet and exercised for 2-hr daily on a treadmill for three days had lower levels of several hepatic lipogenic enzymes (acetyl CoA carboxylase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, malic enzyme and citrate cleavage enzyme) than did sedentary rats pair-fed the diet. Accumulation of triglycerides in plasma following ingestion of a fat-free, high fructose meal and injection of Triton WR-1339, an inhibitor of plasma triglyceride clearance, was not significantly different in the two groups of animals. All of the hepatic lipogenic enzymes measured, with the exception of citrate cleavage enzyme, attained similar levels in the runners as in the controls after 5 days on the high fructose diet. Thus the exercise appeared to affect the time course of the increase in the levels of activity of most of the lipogenic enzymes but not the final steady state levels attained."}
{"id": "PMID:236577", "title": "Gastric antisecretory effect of 15(R)-15-menthyl PGE2, methyl ester and of 15(S)-15-methyl ester.", "content": "Gastric juice was collected from gastric pouches in dogs stimulated with histamine. 15(R)-15-methyl PGE2, methyl ester inhibited gastric secretion in dogs when given orally, but was almost inactive when given intravenously, whereas 15(S)-15-methyl PGE2 methyl ester was active by both routes. When given directly into the small intestine (intrajejunally), the 15(S) was active and the 15(R) was inactive. The 15(R), diluted in acid and administered intrajejunally, became active in inhibiting gastric secretion. When the 15(S) was diluted in acid and administered intrajejunally, it lost half of its activity. When each analog was incubated in an acid medium, each was epimerized to give approximately a 1:1 mixture of both 15(R) and 15(S). Incubation of the 15(R) in pH 3 buffer resulted in only a trace of formation of 15(S). These results explain why the 15(R) is active orally but not intrajejunally. When given orally, the low pH of gastric secretion epimerizes much of the 15(R) into the 15(S),which is active by any route. The degree of acidity of gastric contents may determine whether the 15(R) will exert an antisecretory effect.", "contents": "Gastric antisecretory effect of 15(R)-15-menthyl PGE2, methyl ester and of 15(S)-15-methyl ester. Gastric juice was collected from gastric pouches in dogs stimulated with histamine. 15(R)-15-methyl PGE2, methyl ester inhibited gastric secretion in dogs when given orally, but was almost inactive when given intravenously, whereas 15(S)-15-methyl PGE2 methyl ester was active by both routes. When given directly into the small intestine (intrajejunally), the 15(S) was active and the 15(R) was inactive. The 15(R), diluted in acid and administered intrajejunally, became active in inhibiting gastric secretion. When the 15(S) was diluted in acid and administered intrajejunally, it lost half of its activity. When each analog was incubated in an acid medium, each was epimerized to give approximately a 1:1 mixture of both 15(R) and 15(S). Incubation of the 15(R) in pH 3 buffer resulted in only a trace of formation of 15(S). These results explain why the 15(R) is active orally but not intrajejunally. When given orally, the low pH of gastric secretion epimerizes much of the 15(R) into the 15(S),which is active by any route. The degree of acidity of gastric contents may determine whether the 15(R) will exert an antisecretory effect."}
{"id": "PMID:236578", "title": "Unexpected beta adrenergic effects of the antitumor agent, cyclocytidine, on rat salivary glands.", "content": "In addition to its potent antileukemic properties, cyclocytidine has a sialogogue action that depends on stimulation of beta adrenergic ereceptors of salivary glands. Furthermore, when chronically administered (for 3 days), cyclocytidine caused enlargement of parotid and submaxillary glands and heart that resembled the hypertrophy caused by chronic isoproterenol administration. The salivas evoked by cyclocytidine also closely resembled those evoked by isoproterenol, and were extremely viscous, and high in K+, (121 plus or minus 5.6, for submaxillary, and 42 plus or minus 2.9, for parotid), low in flow rate (0.007 mg/min times mg) and parotid saliva contained high concentrations of amylase (805 plus or minus 33 mg/mg gland). Cyclocytidine also caused marked emptying of parotid gland amylase. The cyclocytidine-induced salivary flow and gland emptying of amylase were prevented for 90 min when propranolol (but not dibenzyline or atropine) was administered prior to injection of the cyclocytidine. In addition, when the superior cervical ganglion was acutely removed, administration of cyclocytidine elicited salivary flow from the denervated as well as the innervated glands. These findings suggest that cyclocytidine does not affect salivary glands through indirect central or ganglionic actions. Cyclocytidine action does not exclusively involve beta receptors, since even in the presence of propranolol, secretory flow was evident after 90 min but when dibenzyline was given with the propranolol, complete blockade of cyclocytidine-stimulated saliva was effected. The dominant effect is, however, a beta adrenergic one. The undesirable side effects of cyclocytidine (parotid pain, postural hypotension, and cardiac hypertrophy) probably stem chiefly from its beta adrenergic properties and might be eliminated (or at least modified) by administration of propranolol with the cyclocytidine.", "contents": "Unexpected beta adrenergic effects of the antitumor agent, cyclocytidine, on rat salivary glands. In addition to its potent antileukemic properties, cyclocytidine has a sialogogue action that depends on stimulation of beta adrenergic ereceptors of salivary glands. Furthermore, when chronically administered (for 3 days), cyclocytidine caused enlargement of parotid and submaxillary glands and heart that resembled the hypertrophy caused by chronic isoproterenol administration. The salivas evoked by cyclocytidine also closely resembled those evoked by isoproterenol, and were extremely viscous, and high in K+, (121 plus or minus 5.6, for submaxillary, and 42 plus or minus 2.9, for parotid), low in flow rate (0.007 mg/min times mg) and parotid saliva contained high concentrations of amylase (805 plus or minus 33 mg/mg gland). Cyclocytidine also caused marked emptying of parotid gland amylase. The cyclocytidine-induced salivary flow and gland emptying of amylase were prevented for 90 min when propranolol (but not dibenzyline or atropine) was administered prior to injection of the cyclocytidine. In addition, when the superior cervical ganglion was acutely removed, administration of cyclocytidine elicited salivary flow from the denervated as well as the innervated glands. These findings suggest that cyclocytidine does not affect salivary glands through indirect central or ganglionic actions. Cyclocytidine action does not exclusively involve beta receptors, since even in the presence of propranolol, secretory flow was evident after 90 min but when dibenzyline was given with the propranolol, complete blockade of cyclocytidine-stimulated saliva was effected. The dominant effect is, however, a beta adrenergic one. The undesirable side effects of cyclocytidine (parotid pain, postural hypotension, and cardiac hypertrophy) probably stem chiefly from its beta adrenergic properties and might be eliminated (or at least modified) by administration of propranolol with the cyclocytidine."}
{"id": "PMID:236580", "title": "The effect of chlorpromazine on some properties DNA in solution.", "content": "The effect of chlorpromazine [2-chloro-10-(3-dimethylaminopropyl)-phenothiazine] on calf thymus DNA has been investigated by spectrophotometric, equilibrium dialysis, thermal denaturation, sedimentation and viscosity methods. The absorption spectra of DNA undergo two important changes upon binding to chlorpromazine, namely, the displacement of peaks to longer wavelength (ranging from 5-8 nm) and a decrease in the optical density. The extent of binding of chlorpromazine to native calf thymus DNA, AS MEASURED BY SPECTROPHOTOMETRIC METHOD, IS DECREASED WITH INCREASING SODIUM CHLORIDE Concentration. A curvature in the Scatchard plot suggests two types of binding processes. Chlorpromazine decreases the optical density at higher temperatures without affecting the Tm of DNA. In its presence, the absorption spectra of purine deoxynucleosides (dA, dG) and of deoxynucleotides (dAMP, dGMP) are modified, i.e., the maxima are displaced to longer wavelength (ranging from 5-17 nm) and there is a general decrease in the optical density. No such effect is observed with pyrimidine deoxynucleosides (dC, dT) and deoxy-nucleotides (dCMP, dTMP). A combination of electrostatic binding of the amino group of chlorpromazine sidechain with the negative phosphate groups of the DNA and a partial insertion of either of its two phenyl rings between the nucleotide base pairs of the DNA plus the binding caused by mutual interaction between different chlorpromazine molecules at higher concentration is proposed as a probable mode of binding of chlorpromazine to DNA.", "contents": "The effect of chlorpromazine on some properties DNA in solution. The effect of chlorpromazine [2-chloro-10-(3-dimethylaminopropyl)-phenothiazine] on calf thymus DNA has been investigated by spectrophotometric, equilibrium dialysis, thermal denaturation, sedimentation and viscosity methods. The absorption spectra of DNA undergo two important changes upon binding to chlorpromazine, namely, the displacement of peaks to longer wavelength (ranging from 5-8 nm) and a decrease in the optical density. The extent of binding of chlorpromazine to native calf thymus DNA, AS MEASURED BY SPECTROPHOTOMETRIC METHOD, IS DECREASED WITH INCREASING SODIUM CHLORIDE Concentration. A curvature in the Scatchard plot suggests two types of binding processes. Chlorpromazine decreases the optical density at higher temperatures without affecting the Tm of DNA. In its presence, the absorption spectra of purine deoxynucleosides (dA, dG) and of deoxynucleotides (dAMP, dGMP) are modified, i.e., the maxima are displaced to longer wavelength (ranging from 5-17 nm) and there is a general decrease in the optical density. No such effect is observed with pyrimidine deoxynucleosides (dC, dT) and deoxy-nucleotides (dCMP, dTMP). A combination of electrostatic binding of the amino group of chlorpromazine sidechain with the negative phosphate groups of the DNA and a partial insertion of either of its two phenyl rings between the nucleotide base pairs of the DNA plus the binding caused by mutual interaction between different chlorpromazine molecules at higher concentration is proposed as a probable mode of binding of chlorpromazine to DNA."}
{"id": "PMID:236581", "title": "The cross-foot flap.", "content": "Reconstruction for losses of the highly specialized skin on the weight-bearing and friction-resistant areas of the foot remains a challenge to the ingenuity of reconstructive surgeons. Although the use of skin from a plantar non-weight-bearing area was described by Mir y Mir 20 years ago, no other reports using the method and emphasizing its advantages have appeared in the literature. On the basis of two cases, both being failures after the use of other methods, we commend the use of a cross-instep flap.", "contents": "The cross-foot flap. Reconstruction for losses of the highly specialized skin on the weight-bearing and friction-resistant areas of the foot remains a challenge to the ingenuity of reconstructive surgeons. Although the use of skin from a plantar non-weight-bearing area was described by Mir y Mir 20 years ago, no other reports using the method and emphasizing its advantages have appeared in the literature. On the basis of two cases, both being failures after the use of other methods, we commend the use of a cross-instep flap."}
{"id": "PMID:236584", "title": "The effect of angiotensin-II during ventriculography in dogs with normal coronary arteries.", "content": "Left ventriculography was performed with and without angiotensin-II in dogs with normal coronary arteries. Concomitant administration of angiotensin significantly attenuated the myocardial depression associated with ventriculography. The beneficial effect of angiotensin may be due to its ability to maintain aortic diastolic pressure and thus flush the contrast material from the myocardium more rapidly, at least in animals without imposed coronary stenosis.", "contents": "The effect of angiotensin-II during ventriculography in dogs with normal coronary arteries. Left ventriculography was performed with and without angiotensin-II in dogs with normal coronary arteries. Concomitant administration of angiotensin significantly attenuated the myocardial depression associated with ventriculography. The beneficial effect of angiotensin may be due to its ability to maintain aortic diastolic pressure and thus flush the contrast material from the myocardium more rapidly, at least in animals without imposed coronary stenosis."}
{"id": "PMID:236582", "title": "Dental health of Louisiana residents based on the ten-state nutrition survey.", "content": "The dental health status of 4,006 residents of Louisiana was analyzed, based on data in the 1968-70 Ten-State Nutrition Survey funded by the U.S. Government. These data were based on examinations of census districts in which the average per capita income was in the lowest quartile for the nation. A considerable variation in the prevalence of dental diseases was found among the Louisiana residents according to age. The females examined had a slightly higher DMF (decayed, missing, and filled permanent teeth) score, a lower OHI (oral hygiene index) score, and a slightly lower PI (periodontal index) score than did the males. The dental caries attack rate did not vary much by race, but the whites examined had received a much greater amount of dental care than had their black counterparts. The OHI scores of the blacks were higher than those for the whites in both the debris and calculus components. The PI scores were higher for the blacks than for the whites. More white persons than blacks were edentulous; this result, however, tends to confirm the observation of increased dental care in white persons. The percentages of persons with periodontal disease and periodontal pockets were considerably higher among persons with incomes below the poverty level, and a greater percentage of blacks had incomes below that level. The data thus apparently indicate that the major determinants of dental health status in Lousiana are age and level of income; race appears to be the major determinant of the amount of dental care received.", "contents": "Dental health of Louisiana residents based on the ten-state nutrition survey. The dental health status of 4,006 residents of Louisiana was analyzed, based on data in the 1968-70 Ten-State Nutrition Survey funded by the U.S. Government. These data were based on examinations of census districts in which the average per capita income was in the lowest quartile for the nation. A considerable variation in the prevalence of dental diseases was found among the Louisiana residents according to age. The females examined had a slightly higher DMF (decayed, missing, and filled permanent teeth) score, a lower OHI (oral hygiene index) score, and a slightly lower PI (periodontal index) score than did the males. The dental caries attack rate did not vary much by race, but the whites examined had received a much greater amount of dental care than had their black counterparts. The OHI scores of the blacks were higher than those for the whites in both the debris and calculus components. The PI scores were higher for the blacks than for the whites. More white persons than blacks were edentulous; this result, however, tends to confirm the observation of increased dental care in white persons. The percentages of persons with periodontal disease and periodontal pockets were considerably higher among persons with incomes below the poverty level, and a greater percentage of blacks had incomes below that level. The data thus apparently indicate that the major determinants of dental health status in Lousiana are age and level of income; race appears to be the major determinant of the amount of dental care received."}
{"id": "PMID:236589", "title": "Differing responses to hypercapnia and hypoxia following pneumotaxic center ablation.", "content": "The respiratory responses of 21 cats were examined upon exposure to hypercapnia and isocapnic hypoxia. Animals having bilateral electrolytic lesions localized in the pontile pneumotaxic center exhibited hypercapnia-induced minute volumes which were significantly less than those of unlesioned control cats. The hypoxia-induced minute volumes of pneumotaxic lesioned animals, examined at isocapnic alveolar gas partial pressures, were likewise significantly less than control animals at end-expired oxygen partial pressures (PAO2) in excess of 65.0 mm Hg. At PAO2 levels below 65.0 mmHg. the minute volume of experimental animals rose sharply and became statistically indistinguishable from that of the unlesioned cats. The placement of control brain stem lesions typically produced no significant alterations in the respiratory responses to hypoxia or hypercapnia. It was concluded that the pneumotaxic center constitutes an integral component of the central chemoreceptor CO1-H+ CONTROLLING SUBSYSTEM. The concept of differing anatomical sites within the brain stem serving integrative functions for central chemoreceptor and peripheral chemoreceptor afferent stimuli is also supported.", "contents": "Differing responses to hypercapnia and hypoxia following pneumotaxic center ablation. The respiratory responses of 21 cats were examined upon exposure to hypercapnia and isocapnic hypoxia. Animals having bilateral electrolytic lesions localized in the pontile pneumotaxic center exhibited hypercapnia-induced minute volumes which were significantly less than those of unlesioned control cats. The hypoxia-induced minute volumes of pneumotaxic lesioned animals, examined at isocapnic alveolar gas partial pressures, were likewise significantly less than control animals at end-expired oxygen partial pressures (PAO2) in excess of 65.0 mm Hg. At PAO2 levels below 65.0 mmHg. the minute volume of experimental animals rose sharply and became statistically indistinguishable from that of the unlesioned cats. The placement of control brain stem lesions typically produced no significant alterations in the respiratory responses to hypoxia or hypercapnia. It was concluded that the pneumotaxic center constitutes an integral component of the central chemoreceptor CO1-H+ CONTROLLING SUBSYSTEM. The concept of differing anatomical sites within the brain stem serving integrative functions for central chemoreceptor and peripheral chemoreceptor afferent stimuli is also supported."}
{"id": "PMID:236590", "title": "Determination of mean whole body intracellular pH  in unanesthetized dogs.", "content": "In order to determine mean whole body pHi in unanesthetized dogs, assumptions on the urinary and intestinal excretion of DMO, the total loss of an injected single dose of [14C] DMO, and the distribution kinetics of DMO were tested experimentally. Urinary excretion of DMO was almost negligible. The best assumption on the total loss of DMO was based on the exponential decay observed over a period of 1 to 4 weeks. The biological half-life of DMO was 5 days, the time constant being --0.14 d-1. The extracellular distribution of DMO was considered to equal that of [3H] inulin. Between 1 and 7 hours after an injection of inulin in nephrectomized dogs the distribution volume increased linearly from 16% of the body weight after 2 hours to 21% after 6 hours. Based on these experimental results, pHi was determined in 16 unanesthetized dogs. 120 min after the injection of DMO pHi was 7.05 and 430 min after the injection pHi was 7.11. It is concluded that the assumption made allow the estimation of pHi in unanesthetized dogs over a period of 1 to 7 hours.", "contents": "Determination of mean whole body intracellular pH  in unanesthetized dogs. In order to determine mean whole body pHi in unanesthetized dogs, assumptions on the urinary and intestinal excretion of DMO, the total loss of an injected single dose of [14C] DMO, and the distribution kinetics of DMO were tested experimentally. Urinary excretion of DMO was almost negligible. The best assumption on the total loss of DMO was based on the exponential decay observed over a period of 1 to 4 weeks. The biological half-life of DMO was 5 days, the time constant being --0.14 d-1. The extracellular distribution of DMO was considered to equal that of [3H] inulin. Between 1 and 7 hours after an injection of inulin in nephrectomized dogs the distribution volume increased linearly from 16% of the body weight after 2 hours to 21% after 6 hours. Based on these experimental results, pHi was determined in 16 unanesthetized dogs. 120 min after the injection of DMO pHi was 7.05 and 430 min after the injection pHi was 7.11. It is concluded that the assumption made allow the estimation of pHi in unanesthetized dogs over a period of 1 to 7 hours."}
{"id": "PMID:236591", "title": "Intracellular pH in unanesthetized dogs during panting.", "content": "Intracellular pH, arterial blood gases and several plasma enzymes were estimated in unanesthetized dogs during a 3-hour exposure to 30 degrees C/50% relative humidity, and 40 degrees C/50% relative humidity. No change occurred during mild heat stress, whereas during severe heat stress a profound respiratory alkalosis developed together with an increase in intracellular pH from 7.03 to 7.29. Most plasma enzymes increased by about 300% or more. In spite of extreme panting body temperature rose to 42.2 degrees C. Exposure to 40 degrees C/50% relative humidity with 4% CO2 in the climatic chamber inhibited the respiratory alkalosis and the increase of plasma enzymes. Though the panting frequency was lower the ventilatory heat dissipation was more efficient. Body temperature rose to only 39.8 degrees C. It is concluded that the intracellular buffering is not able to prevent marked changes of the intracellular pH during panting.", "contents": "Intracellular pH in unanesthetized dogs during panting. Intracellular pH, arterial blood gases and several plasma enzymes were estimated in unanesthetized dogs during a 3-hour exposure to 30 degrees C/50% relative humidity, and 40 degrees C/50% relative humidity. No change occurred during mild heat stress, whereas during severe heat stress a profound respiratory alkalosis developed together with an increase in intracellular pH from 7.03 to 7.29. Most plasma enzymes increased by about 300% or more. In spite of extreme panting body temperature rose to 42.2 degrees C. Exposure to 40 degrees C/50% relative humidity with 4% CO2 in the climatic chamber inhibited the respiratory alkalosis and the increase of plasma enzymes. Though the panting frequency was lower the ventilatory heat dissipation was more efficient. Body temperature rose to only 39.8 degrees C. It is concluded that the intracellular buffering is not able to prevent marked changes of the intracellular pH during panting."}
{"id": "PMID:236593", "title": "Vitamin B12-binding proteins in human gastric mucosa. General pattern and demonstration of intrinsic factor isoproteins typical of mucosa.", "content": "Extracts of human stomach mucosa were shown to contain immunoreactive intrinsic factor and small amounts of R protein and transcobalamin II. In gel filtration the mucosal vitamin B12-intrinsic factor complex behaved as though its molecular weight were smaller than the corresponding complex in gastric juice. In isoelectric focusing both the gastric juice and mucosal vitamin B12-intrinsic factor complexes resolved into numerous isoproteins. These findings were verified by DEAE-cellulose chromatography. The mucosal intrinsic factor isoprotein pattern contained, in addition to the isoproteins found in gastric juice, components with higher isoelectric points -- that is, pH 5.73-6.64.", "contents": "Vitamin B12-binding proteins in human gastric mucosa. General pattern and demonstration of intrinsic factor isoproteins typical of mucosa. Extracts of human stomach mucosa were shown to contain immunoreactive intrinsic factor and small amounts of R protein and transcobalamin II. In gel filtration the mucosal vitamin B12-intrinsic factor complex behaved as though its molecular weight were smaller than the corresponding complex in gastric juice. In isoelectric focusing both the gastric juice and mucosal vitamin B12-intrinsic factor complexes resolved into numerous isoproteins. These findings were verified by DEAE-cellulose chromatography. The mucosal intrinsic factor isoprotein pattern contained, in addition to the isoproteins found in gastric juice, components with higher isoelectric points -- that is, pH 5.73-6.64."}
{"id": "PMID:236594", "title": "Skeletal muscle metabolites in patients with cardiogenic shock or severe congestive heart failure.", "content": "Skeletal muscle metabolite concentrations were determined in 19 patients in either cardiogenic shock or severe left ventricular failure by obtaining a needle biopsy specimen of lateral thigh muscle. Evidence of anaerobic skeletal muscle metabolism was found in both patient groups with the greatest lactate accumulation and most severe high-energy phosphate depletion present in the patients in cardiogenic shock. The skeletal muscle lactate accumulation was most pronounced in the patients that died. Blood lactate values did not absolutely predict skeletal muscle lactate concentrations in those patients in whom skeletal muscle lactate concentrations were the highest. The patients in cardiogenic shock and severe left ventricular failure who survived demonstrated a reduction in skeletal muscle lactate levels and a restoration of high-energy phosphates over several days which correlated with clinical and hemodynamic improvement.", "contents": "Skeletal muscle metabolites in patients with cardiogenic shock or severe congestive heart failure. Skeletal muscle metabolite concentrations were determined in 19 patients in either cardiogenic shock or severe left ventricular failure by obtaining a needle biopsy specimen of lateral thigh muscle. Evidence of anaerobic skeletal muscle metabolism was found in both patient groups with the greatest lactate accumulation and most severe high-energy phosphate depletion present in the patients in cardiogenic shock. The skeletal muscle lactate accumulation was most pronounced in the patients that died. Blood lactate values did not absolutely predict skeletal muscle lactate concentrations in those patients in whom skeletal muscle lactate concentrations were the highest. The patients in cardiogenic shock and severe left ventricular failure who survived demonstrated a reduction in skeletal muscle lactate levels and a restoration of high-energy phosphates over several days which correlated with clinical and hemodynamic improvement."}
{"id": "PMID:236596", "title": "Flexible fiberoptic bronchoscopy with general anesthesia in the poor-risk patient.", "content": "A study is presented of seven poor-risk patients who had bronchoscopy with a flexible fiberoptic bronchoscope and balanced general anesthesia. The cardiorespiratory status, as evidenced by arterial blood gas determinations, electrocardiographic findings, and blood pressure measurements, was improved and stabilized in all patients. Flexible fibeoptic bronchoscopy, combined with general anesthesia, has proved to be a reliable and safe procedure useful for both diagnosis and treatment in poor-risk patients.", "contents": "Flexible fiberoptic bronchoscopy with general anesthesia in the poor-risk patient. A study is presented of seven poor-risk patients who had bronchoscopy with a flexible fiberoptic bronchoscope and balanced general anesthesia. The cardiorespiratory status, as evidenced by arterial blood gas determinations, electrocardiographic findings, and blood pressure measurements, was improved and stabilized in all patients. Flexible fibeoptic bronchoscopy, combined with general anesthesia, has proved to be a reliable and safe procedure useful for both diagnosis and treatment in poor-risk patients."}
{"id": "PMID:236597", "title": "Evaluation and management of the dizzy patient.", "content": "Evaluation and management of the dizzy patient remains frustrating to both the patient and physician. Numerous disorders may induce dizziness; these include not only inner ear disoders but also various central nervous system, ocular, and general systemic disturbances. Since dizziness has many variations, the subtle nuances the symptom may manifest must be explored throughly. Similarly, a consistent approach to the patient's physical and larboratory examination must be taken to understand the pathophysiology of the dizziness. This includes comprehensive auditory and vestibular evaluation, complete neurologic and ophthalmologic examination, and laboratory evaluation for latent or manifest systemic disease. The management of dizziness and vertigo is largely symptomatic. Certain exceptions exist where specific medical and surgical approaches may be beneficial, but the limitations of such treatment must be appreciated.", "contents": "Evaluation and management of the dizzy patient. Evaluation and management of the dizzy patient remains frustrating to both the patient and physician. Numerous disorders may induce dizziness; these include not only inner ear disoders but also various central nervous system, ocular, and general systemic disturbances. Since dizziness has many variations, the subtle nuances the symptom may manifest must be explored throughly. Similarly, a consistent approach to the patient's physical and larboratory examination must be taken to understand the pathophysiology of the dizziness. This includes comprehensive auditory and vestibular evaluation, complete neurologic and ophthalmologic examination, and laboratory evaluation for latent or manifest systemic disease. The management of dizziness and vertigo is largely symptomatic. Certain exceptions exist where specific medical and surgical approaches may be beneficial, but the limitations of such treatment must be appreciated."}
{"id": "PMID:236598", "title": "Immunologic reconstitution in man--present status.", "content": "Recent advances in immunobiology have shed new light on our understanding of the essential role of immunity as it relates to body economy. Immunity, once thought to be the primary defense mechanism against microbial infection, appears to have a much broader function--recognition and elimination of foreign bodies and preservation of the integrity of the individual. As our understanding of the pathophysiology of the immune system became more clear, immunologic reconstitution emerged as a new, promising mode of treatment for a variety of diseases with immunodeficiency. Bone marrow transplantation, thymus transplanation, transfer factor therapy, infusion of leukocytes, BCG vaccination, and other specific or nonspecific immunostimulants have been tried, with dramatic beneficial results in some instances. Although still in its infant stage, this form of treatment appears to have great potential and wide application in the prevention and treatment, not only of primary immunodeficiency, but also of many other diseases such as cancer, the so-called autoimmune diseases, and even aging.", "contents": "Immunologic reconstitution in man--present status. Recent advances in immunobiology have shed new light on our understanding of the essential role of immunity as it relates to body economy. Immunity, once thought to be the primary defense mechanism against microbial infection, appears to have a much broader function--recognition and elimination of foreign bodies and preservation of the integrity of the individual. As our understanding of the pathophysiology of the immune system became more clear, immunologic reconstitution emerged as a new, promising mode of treatment for a variety of diseases with immunodeficiency. Bone marrow transplantation, thymus transplanation, transfer factor therapy, infusion of leukocytes, BCG vaccination, and other specific or nonspecific immunostimulants have been tried, with dramatic beneficial results in some instances. Although still in its infant stage, this form of treatment appears to have great potential and wide application in the prevention and treatment, not only of primary immunodeficiency, but also of many other diseases such as cancer, the so-called autoimmune diseases, and even aging."}
{"id": "PMID:236599", "title": "Adenosine triphosphatase in the embryonic development of the loach.", "content": "The ATPase (ATP-phosphohydrolase) activity of homogenates of eggs of the loach Misgurnus fossilis L. was investigated at various stages of development. Mg-2+- and Ca2- minus 2+-stimulated ATPases are the predominant forms of ATPase activity in the egg, and their level is almost constant during development. The loach egg also contains (Na-+--K-+)-dependent ATPase, which is maximally active at pH 6.85 and at a ratio Na-+:K-+ Equals 5:1. This activity is negligible or absent in homogenates of unfertilized eggs, increases during cleavage, but disappears at the end of the period of cleavage. After this, the (Na-+--K-+)-ATPase activity increases all the way up to the end of the period studied (the gastrula stage)mthe results are discussed in connection with the literature data on changes in ionic homeostasis and other characteristics during early embryogenesis.", "contents": "Adenosine triphosphatase in the embryonic development of the loach. The ATPase (ATP-phosphohydrolase) activity of homogenates of eggs of the loach Misgurnus fossilis L. was investigated at various stages of development. Mg-2+- and Ca2- minus 2+-stimulated ATPases are the predominant forms of ATPase activity in the egg, and their level is almost constant during development. The loach egg also contains (Na-+--K-+)-dependent ATPase, which is maximally active at pH 6.85 and at a ratio Na-+:K-+ Equals 5:1. This activity is negligible or absent in homogenates of unfertilized eggs, increases during cleavage, but disappears at the end of the period of cleavage. After this, the (Na-+--K-+)-ATPase activity increases all the way up to the end of the period studied (the gastrula stage)mthe results are discussed in connection with the literature data on changes in ionic homeostasis and other characteristics during early embryogenesis."}
{"id": "PMID:236601", "title": "Ventricular function in experimental hemorrhagic shock.", "content": "Hemorrhagic shock was induced in 20 spontaneously breathing adult greyhounds by lowering the mean arterial pressure to 40 millimeters of mercury. In the first group of six dogs, reinfusion was carried out without delay; in a second group of six dogs, hypovolemia was continued for two hours, during which time the arterial pressure was permitted to rise in response to intact cardiovascular reflexes; in a third group of eight dogs, the mean arterial pressure was artificially maintained at 40 millimeters of mercury for two hours, initially by further bleeding. In all dogs in the latter group, take-up of blood from the reservoir was required during the second hour to maintain the arterial pressure, this being indicative of irreversible shock. In two of this group, fatal arrhythmias developed during reinfusion. All three groups showed evidence of ventricular dysfunction during and immediately after reinfusion, as indicated by disproportion between left ventricular stroke work and left ventricular end diastolic pressure, these data being used to construct ventricular function curves. Measurement of dP/dt maximum suggested that this dysfunction was due to impairment of myocardial contractility. The first two groups recovered normal function within one hour; the third group failed to have such a recovery. Evidence indicates that generalized tissue hypoxia, in addition to myocardial hypoxia, is important in the cause of cardiac dysfunction in irreversible shock.", "contents": "Ventricular function in experimental hemorrhagic shock. Hemorrhagic shock was induced in 20 spontaneously breathing adult greyhounds by lowering the mean arterial pressure to 40 millimeters of mercury. In the first group of six dogs, reinfusion was carried out without delay; in a second group of six dogs, hypovolemia was continued for two hours, during which time the arterial pressure was permitted to rise in response to intact cardiovascular reflexes; in a third group of eight dogs, the mean arterial pressure was artificially maintained at 40 millimeters of mercury for two hours, initially by further bleeding. In all dogs in the latter group, take-up of blood from the reservoir was required during the second hour to maintain the arterial pressure, this being indicative of irreversible shock. In two of this group, fatal arrhythmias developed during reinfusion. All three groups showed evidence of ventricular dysfunction during and immediately after reinfusion, as indicated by disproportion between left ventricular stroke work and left ventricular end diastolic pressure, these data being used to construct ventricular function curves. Measurement of dP/dt maximum suggested that this dysfunction was due to impairment of myocardial contractility. The first two groups recovered normal function within one hour; the third group failed to have such a recovery. Evidence indicates that generalized tissue hypoxia, in addition to myocardial hypoxia, is important in the cause of cardiac dysfunction in irreversible shock."}
{"id": "PMID:236602", "title": "Adrenergic mechanisms in the cephalic and cerebral circulations of the subhuman primate.", "content": "Effects of circulating adrenergic amines on the cerebral circulation remain contraversial. Common carotid (CCF) and internal carotid (ICF) arterial flows were determined electromagnetically in eight lightly anesthetized baboons to evaluate alterations in the cephalic and cerebral vascular beds, respectively. Epinephrine (E), norepinephrine (NE), phenylephrine (PE), and isoproterenol (I) were injected randomly in doses of 10-3, 10-2, 10-1, and 1 mug (base) per kilogram into each carotid artery. Measurements were repeated in four animals after alpha-adrenergic blockade with phenoxybenzamine and in another four animals after beta-adrenergic blockade with propranolol. Baseline CCF was 75 plus or minus 10 (S.E.M.) ml. per minute and ICF was 58 plus or minus 8 ml. per minute. Significant (p smaller than 0.05) CCF changes without arterial pressure alterations occurred with 10-1 mug per kilogram doses. Alpha blockade significantly (p smaller than 0.05) attenuated the effects of E, NE, and PE on CCF while beta blockade significantly (p smaller than 0.05) attenuated the effect of I on CCF. ICF did not change significantly (p greater than 0.05) after injection of any of the vasoactive amines, unless associated with pressure changes at the highest dose. Our data suggest the presence of alpha- and beta-adrenergic receptor sites within the cephalic circulation resulting in significant flow responses to intra-arterial adrenergic amines. The absence of responses in the cerebral circulation suggests that circulating catecholamines do not significantly influence or regulate the cerebral vasculature. In addition the data suggest that use of adrenergic agonists to alter the hemodynamics of the cerebral circulation is limited.", "contents": "Adrenergic mechanisms in the cephalic and cerebral circulations of the subhuman primate. Effects of circulating adrenergic amines on the cerebral circulation remain contraversial. Common carotid (CCF) and internal carotid (ICF) arterial flows were determined electromagnetically in eight lightly anesthetized baboons to evaluate alterations in the cephalic and cerebral vascular beds, respectively. Epinephrine (E), norepinephrine (NE), phenylephrine (PE), and isoproterenol (I) were injected randomly in doses of 10-3, 10-2, 10-1, and 1 mug (base) per kilogram into each carotid artery. Measurements were repeated in four animals after alpha-adrenergic blockade with phenoxybenzamine and in another four animals after beta-adrenergic blockade with propranolol. Baseline CCF was 75 plus or minus 10 (S.E.M.) ml. per minute and ICF was 58 plus or minus 8 ml. per minute. Significant (p smaller than 0.05) CCF changes without arterial pressure alterations occurred with 10-1 mug per kilogram doses. Alpha blockade significantly (p smaller than 0.05) attenuated the effects of E, NE, and PE on CCF while beta blockade significantly (p smaller than 0.05) attenuated the effect of I on CCF. ICF did not change significantly (p greater than 0.05) after injection of any of the vasoactive amines, unless associated with pressure changes at the highest dose. Our data suggest the presence of alpha- and beta-adrenergic receptor sites within the cephalic circulation resulting in significant flow responses to intra-arterial adrenergic amines. The absence of responses in the cerebral circulation suggests that circulating catecholamines do not significantly influence or regulate the cerebral vasculature. In addition the data suggest that use of adrenergic agonists to alter the hemodynamics of the cerebral circulation is limited."}
{"id": "PMID:236604", "title": "Positive chronotropic and inotropic effects of glucagon on the canine isolated atrium.", "content": "Effects of glucagon on SA node pacemaker activity and atrial contractility were investigated in isolated canine atrium preparations which were perfused with blood led from a support dog and suspended in a bath. Glucagon at a dose from 0.1 to 10 mug was injected into the sinus node artery, which caused a marked positive chronotropic but a less inotropic effect. The positive inotropic response was simulated by atrial acceleration produced by atrial pacing. Glucagon effects were not influenced by treatment with an adrenergic beta-blocking agent, alprenolol to SQ 11725, which blocked effects of norepinephrine. It was concluded that glucagon is more effective on pacemaker activity than on atrial contractile force, and glucagon effects may not be mediated by an adrenergic beta-mechanism.", "contents": "Positive chronotropic and inotropic effects of glucagon on the canine isolated atrium. Effects of glucagon on SA node pacemaker activity and atrial contractility were investigated in isolated canine atrium preparations which were perfused with blood led from a support dog and suspended in a bath. Glucagon at a dose from 0.1 to 10 mug was injected into the sinus node artery, which caused a marked positive chronotropic but a less inotropic effect. The positive inotropic response was simulated by atrial acceleration produced by atrial pacing. Glucagon effects were not influenced by treatment with an adrenergic beta-blocking agent, alprenolol to SQ 11725, which blocked effects of norepinephrine. It was concluded that glucagon is more effective on pacemaker activity than on atrial contractile force, and glucagon effects may not be mediated by an adrenergic beta-mechanism."}
{"id": "PMID:236607", "title": "The effect of continuous dialysis on platelet preservation.", "content": "Serotonin uptake and response to hypotonic shock were studied after storage of platelet-rich plasma for three days at 4, 25, and 37 C. Both properties were best maintained at 25 C. The greatly impaired serotonin uptake and hypotonic shock response of platelets stored for three days at 37 C were partly restored by resuspension of the platelets in fresh autologous plasma. No improvement was found when platelets stored at 4 C were resuspended in fresh autologous plasma. When platelet suspensions were stored for three days at 4, 25, and 37 C under continuous dialysis against plasma, the results obtained at 37 C were even better than those obtained with platelets stored at 25 C. These results indicate that if the accumulation of metabolites in the plasma milieu, which in addition to other changes results in a drop of pH, is prevented, the effective storage time of platelet concentrates can be prolonged. The use of a closed plastic dialysis system, based on the triple-bag transfusion set is suggested.", "contents": "The effect of continuous dialysis on platelet preservation. Serotonin uptake and response to hypotonic shock were studied after storage of platelet-rich plasma for three days at 4, 25, and 37 C. Both properties were best maintained at 25 C. The greatly impaired serotonin uptake and hypotonic shock response of platelets stored for three days at 37 C were partly restored by resuspension of the platelets in fresh autologous plasma. No improvement was found when platelets stored at 4 C were resuspended in fresh autologous plasma. When platelet suspensions were stored for three days at 4, 25, and 37 C under continuous dialysis against plasma, the results obtained at 37 C were even better than those obtained with platelets stored at 25 C. These results indicate that if the accumulation of metabolites in the plasma milieu, which in addition to other changes results in a drop of pH, is prevented, the effective storage time of platelet concentrates can be prolonged. The use of a closed plastic dialysis system, based on the triple-bag transfusion set is suggested."}
{"id": "PMID:236608", "title": "Chemical and hematological changes in stored CPD blood.", "content": "Blood was drawn from ten healthy volunteer donors into citrate-phosphate-dextrose (CPD) anticoagulant and placed on the quarantine shelf of the blood bank refrigerator. Plasma dextrose, sodium, potassium, chloride, bicarbonate, GOT, LDH, and hemoglobin as well as WBC, hematocrit, MCV, MCHC, whole blood pH, and ammonia were measured on all samples initially and at one, two, seven, 14, 21, and 28 days of storage at 4 C. Whole blood lactate also was analyzed serially on five of the units. An additional 27 units of CPD bank blood (two to 21 days of age), routinely processed, handled, and stored by the blood bank, were submitted to the same analyses on the day of administration to the patient. Five of these processed units, 21 days old, were resampled at 28 days. Results of the analyses are presented and discussed. The most pronounced changes were seen for dextrose, potassium, bicarbonate, lactate, LDH, ammonia, and hemoglobin. Plasma dextrose and bicarbonate declined in concentration while potassium, lactate, LDH, ammonia, and hemoglobin rose with storage. In general, changes in the regularly processed, singly sampled bank units were greater than those observed in the specially processed, quarantined units sampled serially. This study indicates that routine transportation, processing, and handling of bank blood may lead to increased biochemical alteration.", "contents": "Chemical and hematological changes in stored CPD blood. Blood was drawn from ten healthy volunteer donors into citrate-phosphate-dextrose (CPD) anticoagulant and placed on the quarantine shelf of the blood bank refrigerator. Plasma dextrose, sodium, potassium, chloride, bicarbonate, GOT, LDH, and hemoglobin as well as WBC, hematocrit, MCV, MCHC, whole blood pH, and ammonia were measured on all samples initially and at one, two, seven, 14, 21, and 28 days of storage at 4 C. Whole blood lactate also was analyzed serially on five of the units. An additional 27 units of CPD bank blood (two to 21 days of age), routinely processed, handled, and stored by the blood bank, were submitted to the same analyses on the day of administration to the patient. Five of these processed units, 21 days old, were resampled at 28 days. Results of the analyses are presented and discussed. The most pronounced changes were seen for dextrose, potassium, bicarbonate, lactate, LDH, ammonia, and hemoglobin. Plasma dextrose and bicarbonate declined in concentration while potassium, lactate, LDH, ammonia, and hemoglobin rose with storage. In general, changes in the regularly processed, singly sampled bank units were greater than those observed in the specially processed, quarantined units sampled serially. This study indicates that routine transportation, processing, and handling of bank blood may lead to increased biochemical alteration."}
{"id": "PMID:236609", "title": "Evaluation of bacterial contamination in blood processing.", "content": "In the routine deglycerolization of frozen red blood cells, a bottle of solution intended as a final wash (0.8% NaCl, 0.2% dextrose) was found to be abnormally colored and slightly turbid. Close inspection revealed a small crack in the base of the bottle. A pure growth of Klebsiella pneumoniae was cultured. The rabbit pyrogen test on the solution was positive using 2.5 mul as was the limulus amebocyte lysate (LAL) test at a dilution of 1:10-5 for endotoxin. Studies of the growth of this organism are described and the clinical implications are discussed.", "contents": "Evaluation of bacterial contamination in blood processing. In the routine deglycerolization of frozen red blood cells, a bottle of solution intended as a final wash (0.8% NaCl, 0.2% dextrose) was found to be abnormally colored and slightly turbid. Close inspection revealed a small crack in the base of the bottle. A pure growth of Klebsiella pneumoniae was cultured. The rabbit pyrogen test on the solution was positive using 2.5 mul as was the limulus amebocyte lysate (LAL) test at a dilution of 1:10-5 for endotoxin. Studies of the growth of this organism are described and the clinical implications are discussed."}
{"id": "PMID:236615", "title": "Cholinergic and adrenergic neuroreceptors in urinary tract of female dogs.  Evaluation of function with pharmacodynamics.", "content": "Our preliminary pharmacodynamic studies on the lower urinary tract of adult female dogs indicate that cholinergic and adrenergic (alpha and beta) neuroreceptors in the urethra appear to coordinate the detrusor and urethral function during micturition.  Urethral resistance  measured as urethral pressure was easily altered with various pharmacologic agents.  However, only bethanechol elicited detrusor response measured as intravesical pressure.  The possible clinical usefulness of various drugs is outlined.  Our results indicate the therapeutic value of ephedrine sulfate and propranolol in stress urinary incontinence; phenoxybenzamine in neurogenic vesical dysfunction and functional outlet obstruction; phenoxybenzamine plus bethanechol in atonic neurogenic bladder; and imipramine in enuresis.", "contents": "Cholinergic and adrenergic neuroreceptors in urinary tract of female dogs.  Evaluation of function with pharmacodynamics. Our preliminary pharmacodynamic studies on the lower urinary tract of adult female dogs indicate that cholinergic and adrenergic (alpha and beta) neuroreceptors in the urethra appear to coordinate the detrusor and urethral function during micturition.  Urethral resistance  measured as urethral pressure was easily altered with various pharmacologic agents.  However, only bethanechol elicited detrusor response measured as intravesical pressure.  The possible clinical usefulness of various drugs is outlined.  Our results indicate the therapeutic value of ephedrine sulfate and propranolol in stress urinary incontinence; phenoxybenzamine in neurogenic vesical dysfunction and functional outlet obstruction; phenoxybenzamine plus bethanechol in atonic neurogenic bladder; and imipramine in enuresis."}
{"id": "PMID:236616", "title": "Noonan's syndrome associated with cake kidney.", "content": "Noonan's syndrome is an established clinical entity.  These cases are often associated with correctable cardiac abnormalities, cryptorchism, and abnormal urinary tract.  Herein is described the first case of Noonan's syndrome associated with cake kidney.  The very high incidence of renal tract abnormalities in association with this syndrome warrants an excretory urogram in these cases for proper evaluation and management.", "contents": "Noonan's syndrome associated with cake kidney. Noonan's syndrome is an established clinical entity.  These cases are often associated with correctable cardiac abnormalities, cryptorchism, and abnormal urinary tract.  Herein is described the first case of Noonan's syndrome associated with cake kidney.  The very high incidence of renal tract abnormalities in association with this syndrome warrants an excretory urogram in these cases for proper evaluation and management."}
{"id": "PMID:236617", "title": "Treatment of cryptorchidism.  Long-term prospective study.", "content": "We have presented preliminary findings on a long-term prospective study designed to (1) assess timing of orchiopexy, (2) eliminate unnecessary abdominal exploratory surgery, and (3) determine efficacy of orchiopexy on subsequent fertility and on malignant degeneration.  Some suggestions for the management of this common congenital defect can be provided, but long-term results are lacking.  A significant drop-out rate from this prospective study is expected with time; therefore, large patient numbers are needed to draw any valid conclusions at the time of postpubertal reassessment.", "contents": "Treatment of cryptorchidism.  Long-term prospective study. We have presented preliminary findings on a long-term prospective study designed to (1) assess timing of orchiopexy, (2) eliminate unnecessary abdominal exploratory surgery, and (3) determine efficacy of orchiopexy on subsequent fertility and on malignant degeneration.  Some suggestions for the management of this common congenital defect can be provided, but long-term results are lacking.  A significant drop-out rate from this prospective study is expected with time; therefore, large patient numbers are needed to draw any valid conclusions at the time of postpubertal reassessment."}
{"id": "PMID:236618", "title": "[Physico-chemical properties of CELO virus strains isolated in Bulgaria].", "content": "Studied were some physico-chemical properties of four CELO virus strains isolated in Bulgaria. Their behaviour to ether, chloroform and 25 per cent trypsin, and their state at 56 degrees C and at pH 3, 0 were determined through their infectious titer as obtained on 9--10-day old chicken embryos. It was found that the size of the investigated viruses is within the range of 50 to 100 mmu, they belong to the DNA-possessing group, are resistant at 56 degrees C and at pH EQUALS 3,0. They are not sensitive to ether, chloroform and trypsin. Their physico-chemical properties are fully comparable with those of the avian adenoviruses-CELO.", "contents": "[Physico-chemical properties of CELO virus strains isolated in Bulgaria]. Studied were some physico-chemical properties of four CELO virus strains isolated in Bulgaria. Their behaviour to ether, chloroform and 25 per cent trypsin, and their state at 56 degrees C and at pH 3, 0 were determined through their infectious titer as obtained on 9--10-day old chicken embryos. It was found that the size of the investigated viruses is within the range of 50 to 100 mmu, they belong to the DNA-possessing group, are resistant at 56 degrees C and at pH EQUALS 3,0. They are not sensitive to ether, chloroform and trypsin. Their physico-chemical properties are fully comparable with those of the avian adenoviruses-CELO."}
{"id": "PMID:236620", "title": "[The effect of transplanting cells from several tissues on the growth of snygenous sarcoma in mice].", "content": "Inhibition of syngenic sarcoma growth was observed in injection of 40 mil. of lymph node cells. Cells of the spleen and bone marrow rendered a less pronounced effect. Thymic cells proved to be less effective. No enhancement of antitumor effect was noted in simultaneous injection of thymic cells with those of the spleen and bone marrow. An addition of thymic cells to lymph node lessens reliably the tumor incidence, also conditioning a tendency to reduction of frequency of its progressive growth.", "contents": "[The effect of transplanting cells from several tissues on the growth of snygenous sarcoma in mice]. Inhibition of syngenic sarcoma growth was observed in injection of 40 mil. of lymph node cells. Cells of the spleen and bone marrow rendered a less pronounced effect. Thymic cells proved to be less effective. No enhancement of antitumor effect was noted in simultaneous injection of thymic cells with those of the spleen and bone marrow. An addition of thymic cells to lymph node lessens reliably the tumor incidence, also conditioning a tendency to reduction of frequency of its progressive growth."}
{"id": "PMID:236621", "title": "[Comparable ergometric examinations before and after administration of practolol and bunitrolol (author's transl)].", "content": "By means of a standardized, single-level ergometric load of 1.5 watt/kg body weight, the effects of a new beta-adrenergic receptor blocking agent bunitrolol (o-(2-hydroxy-3-tertiary butylamino)-propoxy)-benzonitrile) was compared with the well-known cardiovascular properties of practolol during an intraindividual therapeutic crossover trial after intravenous administration. In the absence of any side-effects, bunitrolol shows a higher degree of beta-adrenergic receptor bocking activity than practolol, with a distinct specificity towards myocardial receptors and very low cardiodepressive properties at rest. Bunitrolol caused a marked reduction (33%) in exercise-induced myocardial work effort, whilst practolol achieved a reduction of only 17% under equal conditions. Thus, the same physical work load is performed after bunitrolol more economically by decreasing both heart rate and blood pressure. The circulatory effects of an intravenous dose of 5 mg bunitrolol seems to be twice as effective as 10 mg practolol. This implies that beta-adrenergic receptor blockade by bunitrolol during work performance is four times as effective as practolol. The observed marked effect of bunitrolol on the diastolic blood pressure is discussed.", "contents": "[Comparable ergometric examinations before and after administration of practolol and bunitrolol (author's transl)]. By means of a standardized, single-level ergometric load of 1.5 watt/kg body weight, the effects of a new beta-adrenergic receptor blocking agent bunitrolol (o-(2-hydroxy-3-tertiary butylamino)-propoxy)-benzonitrile) was compared with the well-known cardiovascular properties of practolol during an intraindividual therapeutic crossover trial after intravenous administration. In the absence of any side-effects, bunitrolol shows a higher degree of beta-adrenergic receptor bocking activity than practolol, with a distinct specificity towards myocardial receptors and very low cardiodepressive properties at rest. Bunitrolol caused a marked reduction (33%) in exercise-induced myocardial work effort, whilst practolol achieved a reduction of only 17% under equal conditions. Thus, the same physical work load is performed after bunitrolol more economically by decreasing both heart rate and blood pressure. The circulatory effects of an intravenous dose of 5 mg bunitrolol seems to be twice as effective as 10 mg practolol. This implies that beta-adrenergic receptor blockade by bunitrolol during work performance is four times as effective as practolol. The observed marked effect of bunitrolol on the diastolic blood pressure is discussed."}
{"id": "PMID:236622", "title": "[Theoretical aspects of fighting cancer recurrence (author's transl)].", "content": "The noticeable improvement in the supply of glucose and oxygen to surviving cancer cells located far from the capillary region (primarily very slowly proliferating or non-proliferating cancer cells) can be taken as the main reason for cancer recurrence in the wake of successful tumour treatment with destruction of a high percentage of cancer cells. On the basis of theoretical and experimental research work on substrate supply, cell kinetics and therapy mechanisms in the intercapillary region, therapeutic steps are formulated which act on cancer cells situated at a greater distance from the capillaries and, therefore, against the genesis of cancer recurrence as such.", "contents": "[Theoretical aspects of fighting cancer recurrence (author's transl)]. The noticeable improvement in the supply of glucose and oxygen to surviving cancer cells located far from the capillary region (primarily very slowly proliferating or non-proliferating cancer cells) can be taken as the main reason for cancer recurrence in the wake of successful tumour treatment with destruction of a high percentage of cancer cells. On the basis of theoretical and experimental research work on substrate supply, cell kinetics and therapy mechanisms in the intercapillary region, therapeutic steps are formulated which act on cancer cells situated at a greater distance from the capillaries and, therefore, against the genesis of cancer recurrence as such."}
{"id": "PMID:236625", "title": "Preparation and characteristics of the structure of methoxyamine-modified f2 RNA.", "content": "Treatment of phage f2 RNA with [14-C]methoxyamine under non-denaturing conditions resulted in modification of exposed cytosines only. On methoxyamine treatment in the presence of 6 M-guanidine, all cytosines were modified. Under the conditions applied, no modification of adenine base in RNA chain occurred. The structure of modified f2 RNA preparations was studied by melting and sedimentation analysis. The ratio between the modification products (N-4-methoxycytosine and N-4-methoxy-6-methoxyamino-5,6-dihydrocytosine) was determined in RNA preparations modified under non-denaturing and denaturing conditions.", "contents": "Preparation and characteristics of the structure of methoxyamine-modified f2 RNA. Treatment of phage f2 RNA with [14-C]methoxyamine under non-denaturing conditions resulted in modification of exposed cytosines only. On methoxyamine treatment in the presence of 6 M-guanidine, all cytosines were modified. Under the conditions applied, no modification of adenine base in RNA chain occurred. The structure of modified f2 RNA preparations was studied by melting and sedimentation analysis. The ratio between the modification products (N-4-methoxycytosine and N-4-methoxy-6-methoxyamino-5,6-dihydrocytosine) was determined in RNA preparations modified under non-denaturing and denaturing conditions."}
{"id": "PMID:236627", "title": "Purification and some properties of arginase from human lung.", "content": "Arginase from human lung has been isolated and purified about 100-fold. During the purification procedure the enzyme was stabilized by Mn2+. The molecular weight determined by Sephadex G-150 gel filtration was found to be 120 000. The enzyme is highly specific towards L-arginine. Incubation of the enzyme with EDTA for 60 min at pH 7.5 and 37 degrees C results in dissociation into inactive subunits of mol. wt. 30 000. On addition of Mn2+ ion to the inactivated enzyme, the subunits reassociate into the native form of the enzyme of mol. wt. 120 000, and the activity is restored.", "contents": "Purification and some properties of arginase from human lung. Arginase from human lung has been isolated and purified about 100-fold. During the purification procedure the enzyme was stabilized by Mn2+. The molecular weight determined by Sephadex G-150 gel filtration was found to be 120 000. The enzyme is highly specific towards L-arginine. Incubation of the enzyme with EDTA for 60 min at pH 7.5 and 37 degrees C results in dissociation into inactive subunits of mol. wt. 30 000. On addition of Mn2+ ion to the inactivated enzyme, the subunits reassociate into the native form of the enzyme of mol. wt. 120 000, and the activity is restored."}
{"id": "PMID:236628", "title": "Secretion of progesterone by human overies perfused in vitro.", "content": "A system for the perfusion of isolated human ovaries is described. Krebs-Ringer bicarbonate buffer (pH 7.4) containing glucose, sodium lactate and pyruvate was perfused at a flow rate of 5-8 ml/min at 37 degrees C through the ovarian artery. Oxygen uptake, LDH-activity, pH and progesterone secretion were determined as parameters of viability of the perfused organ. Our results demonstrate that a relatively simple system used for perfusion was able to preserve ovarian function for at least two hours. This experimental design should not be regarded as physiological but in addition to other experimental approaches it might provide information on the physiology of the human ovary. Though lower values of progesterone secretion than in vivo were found, a correlation of secretion and functional stage of the ovaries could be demonstrated.", "contents": "Secretion of progesterone by human overies perfused in vitro. A system for the perfusion of isolated human ovaries is described. Krebs-Ringer bicarbonate buffer (pH 7.4) containing glucose, sodium lactate and pyruvate was perfused at a flow rate of 5-8 ml/min at 37 degrees C through the ovarian artery. Oxygen uptake, LDH-activity, pH and progesterone secretion were determined as parameters of viability of the perfused organ. Our results demonstrate that a relatively simple system used for perfusion was able to preserve ovarian function for at least two hours. This experimental design should not be regarded as physiological but in addition to other experimental approaches it might provide information on the physiology of the human ovary. Though lower values of progesterone secretion than in vivo were found, a correlation of secretion and functional stage of the ovaries could be demonstrated."}
{"id": "PMID:236629", "title": "Studies on 17beta-hydroxysteroid dehydrogenase in human endometrium and endometrial carcinoma.", "content": "Kinetic parameters, substrate specificity and stability of a cytoplasmic 17beta-hydroxysteroid dehydrogenase of human secretory endometrium were studied. Using oestradiol as substrate, oestrone formation was found to be linear with time and the concentration of protein. The optimum temperature was 40 degrees C and the optimum pH 9.5. For the reduction of oestrone the optimal pH was 6. With NADP the maximal velocity was about 1/3 of that with NAD (0.23 nmoles/mg protein/10 min). The Km for oestradiol was 3.3 times 10- minus 6 M. Testosterone and androstenedione also served as substrates but they were interconverted more slowly than oestradiol and oestrone. Sulphhydryl groups were shown to be essential for catalysis. The enzyme is cold sensitive but cold inactivation can be reduced by NAD, NADP, oestradiol or glycerol.", "contents": "Studies on 17beta-hydroxysteroid dehydrogenase in human endometrium and endometrial carcinoma. Kinetic parameters, substrate specificity and stability of a cytoplasmic 17beta-hydroxysteroid dehydrogenase of human secretory endometrium were studied. Using oestradiol as substrate, oestrone formation was found to be linear with time and the concentration of protein. The optimum temperature was 40 degrees C and the optimum pH 9.5. For the reduction of oestrone the optimal pH was 6. With NADP the maximal velocity was about 1/3 of that with NAD (0.23 nmoles/mg protein/10 min). The Km for oestradiol was 3.3 times 10- minus 6 M. Testosterone and androstenedione also served as substrates but they were interconverted more slowly than oestradiol and oestrone. Sulphhydryl groups were shown to be essential for catalysis. The enzyme is cold sensitive but cold inactivation can be reduced by NAD, NADP, oestradiol or glycerol."}
{"id": "PMID:236630", "title": "The role of reduced glutathione in thyroglobulin proteolysis iv vitro.", "content": "During the process of secretion of the thyroid hormones, stored thyroglobulin (Tg) is digested within the lysosomes. An acid protease has been found, but this enzyme hydrolyses Tg at a relatively slow rate and has a low pH optimum (3.6). Since previous work has shown a stimulatory effect of reduced glutathione (GSH) on Tg digestion the following studies have been performed. Homogenates were obtained from dog thyroid and total homogenate or different subcellular fractions were used as enzyme source. Labelled thyroglobulin (125-I) was purufied from prelabelled dog thyroid and its hydrolysis, judged from the increase in butanol soluble radioactivity, was studied. The greatest stimulatory effect of GSH on Tg hydrolysis was found around pH 5.6. When butanol soluble radioactivity was considered as a function of incubation time and tissue concentration a linear relationship was found. GSH effect was evident at 2 mM. Subcellular distribution studies showed that the GSH-stimulated proteolytic activity was mainly found in the 15 000 times g pellet. Labelled Tg hydrolysis was progressively decreased with increasing amounts of non-labelled purified Tg. GSH also stimulated labelled insulin hydrolysis, but failed to alter haemoglobin or casein degradation. GSH could also be replaced by other reducing agents, like cysteine or dithiothreitol. The significance of these findings is discussed in relation to the process of thyroid hormone secretion.", "contents": "The role of reduced glutathione in thyroglobulin proteolysis iv vitro. During the process of secretion of the thyroid hormones, stored thyroglobulin (Tg) is digested within the lysosomes. An acid protease has been found, but this enzyme hydrolyses Tg at a relatively slow rate and has a low pH optimum (3.6). Since previous work has shown a stimulatory effect of reduced glutathione (GSH) on Tg digestion the following studies have been performed. Homogenates were obtained from dog thyroid and total homogenate or different subcellular fractions were used as enzyme source. Labelled thyroglobulin (125-I) was purufied from prelabelled dog thyroid and its hydrolysis, judged from the increase in butanol soluble radioactivity, was studied. The greatest stimulatory effect of GSH on Tg hydrolysis was found around pH 5.6. When butanol soluble radioactivity was considered as a function of incubation time and tissue concentration a linear relationship was found. GSH effect was evident at 2 mM. Subcellular distribution studies showed that the GSH-stimulated proteolytic activity was mainly found in the 15 000 times g pellet. Labelled Tg hydrolysis was progressively decreased with increasing amounts of non-labelled purified Tg. GSH also stimulated labelled insulin hydrolysis, but failed to alter haemoglobin or casein degradation. GSH could also be replaced by other reducing agents, like cysteine or dithiothreitol. The significance of these findings is discussed in relation to the process of thyroid hormone secretion."}
{"id": "PMID:236631", "title": "Additional data on hepatic function tests in cystic fibrosis.", "content": "Fifty cystic fibrosis (CF) patients, of whom 9 had multilobular cirrhosis, were observed regularly for a period of 3 years and various liver function tests, indicating cytolysis, cholestasis and cellular insufficiency were performed. Immunoglobulin and prothrombin were assayed. In 9 patients with cirrhosis, the tests were generally abnormal. Two distinct biochemical patterns of cirrhosis were distinguished, one clearly cholestatic and the other of a more cellular type. The distinction was made on the basis of the IgA : Transferrin ratio and of gamma-glutamyl-transpeptidase levels. In the non-cirrhotic patients, a temporary increase of cytolysis and cholestasis was observed in 50% of the cases.", "contents": "Additional data on hepatic function tests in cystic fibrosis. Fifty cystic fibrosis (CF) patients, of whom 9 had multilobular cirrhosis, were observed regularly for a period of 3 years and various liver function tests, indicating cytolysis, cholestasis and cellular insufficiency were performed. Immunoglobulin and prothrombin were assayed. In 9 patients with cirrhosis, the tests were generally abnormal. Two distinct biochemical patterns of cirrhosis were distinguished, one clearly cholestatic and the other of a more cellular type. The distinction was made on the basis of the IgA : Transferrin ratio and of gamma-glutamyl-transpeptidase levels. In the non-cirrhotic patients, a temporary increase of cytolysis and cholestasis was observed in 50% of the cases."}
{"id": "PMID:236632", "title": "Production of cell-bound antigens by Bacteroides fragilis nctc 9343 in continuous culture.", "content": "Highly active antigen preparations, as measured by precipitation and inhibition of haemaglutination, were obtained from Bacteroides fragilis NCTC 9343 grown in continuous culture. The activity varied slightly only with the glucose concentration of the medium and the dilution rate. pH had a greater influence on antigen production.", "contents": "Production of cell-bound antigens by Bacteroides fragilis nctc 9343 in continuous culture. Highly active antigen preparations, as measured by precipitation and inhibition of haemaglutination, were obtained from Bacteroides fragilis NCTC 9343 grown in continuous culture. The activity varied slightly only with the glucose concentration of the medium and the dilution rate. pH had a greater influence on antigen production."}
{"id": "PMID:236635", "title": "The effect of low-calcium diet and vitamin-D-3 on acid-base balance in young rabbits.", "content": "The effect of low-calcium diet and vitamin D-3 on acid-base balance in young rabbits. Acta Physiol. Pol. 1975, 26 (1): 103-108. The effect of secondary hyperparathyroidism and vitamin D-3 on the acid-base balance was investigated in young rabbits. No metabolic acidosis was found in animals given vitamin D-3 in addition to low-calcium diet.", "contents": "The effect of low-calcium diet and vitamin-D-3 on acid-base balance in young rabbits. The effect of low-calcium diet and vitamin D-3 on acid-base balance in young rabbits. Acta Physiol. Pol. 1975, 26 (1): 103-108. The effect of secondary hyperparathyroidism and vitamin D-3 on the acid-base balance was investigated in young rabbits. No metabolic acidosis was found in animals given vitamin D-3 in addition to low-calcium diet."}
{"id": "PMID:236644", "title": "Adenylate cyclase activation in lymphoid tissues during graft-versus-host reaction.", "content": "Graft-versus-host reactions were induced in adult F1 hybrid animals by injecting parental spleen cells. Adenylate cyclase activity was determined in the washed cell particles of the lymphoid tissues. During a time course study of the regional GVH reaction an increase in lymph node weight was apparent at day 2, whereas the adenylate cyclase activity increased at day 4 after the injection. Maximal lymph node hypertrophy and adenylate cyclase activation were observed 8 to 10 days after initiation of the GVH response. Adenylate cyclase stimulation by epinephrine of the GVH response. Adenylate cyclase stimulation by epinephrine and glucagon in experimental preparations was less than in the control. NaF was stimulatory only in the control preparations. Ca-2+ in concentrations up to 8 mM had no inhibitory effects on the control or experimental preparations. The pattern of responses of the experimental preparations to Zn-2+ and Cu-2+ was different than the control; however, in high concentrations both of these cations had marked inhibitory effects. An increase in the adenylate cyclase activity was also direct relationship between the adenylate cyclase activity and the cytolytic activity of spleen cells from mice undergoing systemic GVH reaction. These results can be explained on the basis of alterations in the cell membranes, and it is suggested that such changes play an important role in the pathogenesis of GVH disease.", "contents": "Adenylate cyclase activation in lymphoid tissues during graft-versus-host reaction. Graft-versus-host reactions were induced in adult F1 hybrid animals by injecting parental spleen cells. Adenylate cyclase activity was determined in the washed cell particles of the lymphoid tissues. During a time course study of the regional GVH reaction an increase in lymph node weight was apparent at day 2, whereas the adenylate cyclase activity increased at day 4 after the injection. Maximal lymph node hypertrophy and adenylate cyclase activation were observed 8 to 10 days after initiation of the GVH response. Adenylate cyclase stimulation by epinephrine of the GVH response. Adenylate cyclase stimulation by epinephrine and glucagon in experimental preparations was less than in the control. NaF was stimulatory only in the control preparations. Ca-2+ in concentrations up to 8 mM had no inhibitory effects on the control or experimental preparations. The pattern of responses of the experimental preparations to Zn-2+ and Cu-2+ was different than the control; however, in high concentrations both of these cations had marked inhibitory effects. An increase in the adenylate cyclase activity was also direct relationship between the adenylate cyclase activity and the cytolytic activity of spleen cells from mice undergoing systemic GVH reaction. These results can be explained on the basis of alterations in the cell membranes, and it is suggested that such changes play an important role in the pathogenesis of GVH disease."}
{"id": "PMID:236645", "title": "Headaches in children.", "content": "\"Common\" nonspecific headaches are the most frequent headaches in childhood and do not require a visit to the physician. Migraine is the most common of the headache syndromes with characteristic profiles, followed by the muscle contraction (tension), inflammatory and psychogenic types. Less frequent are mass or brain tumor headaches, malformation and hypertensive headaches. Migraine goes unrecognized more than the other common syndromes. Minor tranquilization may stop the pattern. The most important aspect of treatment for muscle contraction headache is recognition.", "contents": "Headaches in children. \"Common\" nonspecific headaches are the most frequent headaches in childhood and do not require a visit to the physician. Migraine is the most common of the headache syndromes with characteristic profiles, followed by the muscle contraction (tension), inflammatory and psychogenic types. Less frequent are mass or brain tumor headaches, malformation and hypertensive headaches. Migraine goes unrecognized more than the other common syndromes. Minor tranquilization may stop the pattern. The most important aspect of treatment for muscle contraction headache is recognition."}
{"id": "PMID:236647", "title": "Nutritional stability of various naturally occurring monoglutamate derivatives of folic acid.", "content": "The nutritional stabilities of four major dietary folates were studied as their corresponding monoglutamates and were compared to pteroylglutamate (folic acid) itself. The study of the monoglutamyl rather than polyglutamyl forms was justified since the former are formed during the course of digestion and also addition of extra glutamyl residues is unlikely to affect the types of nutritional instability associated with these derivatives. Since ability to support growth in Lactobacillus casei is known to reflect nutritional activity in man this organism was used in the stability studies. It was found that pteroylglutamate and 5-formyltetrahydropteroylglutamate had nutritional stabilities of the order of weeks although the stability of the former was decreased by phosphate. Surprisingly 10-formyltetrahydropteroylglutamate was nutritionally more stable than expected, possibly due to its conversion to the more stable oxidized 10-formylpteroylglutamate or to the reduced 5-formyl derivative. In contrast 5-methyltetrahydropteroylglutamate was much less stable nutritionally than expected.Unsubstituted tetrahydropteroylglutamate was most unstable nutritionally but in contrast to the other derivatives examined it was more stable under acidic than basic conditions. Ascorbate was found to be a far superior stabilizing agent than 2-mercaptoethanol at comparable concentrations.", "contents": "Nutritional stability of various naturally occurring monoglutamate derivatives of folic acid. The nutritional stabilities of four major dietary folates were studied as their corresponding monoglutamates and were compared to pteroylglutamate (folic acid) itself. The study of the monoglutamyl rather than polyglutamyl forms was justified since the former are formed during the course of digestion and also addition of extra glutamyl residues is unlikely to affect the types of nutritional instability associated with these derivatives. Since ability to support growth in Lactobacillus casei is known to reflect nutritional activity in man this organism was used in the stability studies. It was found that pteroylglutamate and 5-formyltetrahydropteroylglutamate had nutritional stabilities of the order of weeks although the stability of the former was decreased by phosphate. Surprisingly 10-formyltetrahydropteroylglutamate was nutritionally more stable than expected, possibly due to its conversion to the more stable oxidized 10-formylpteroylglutamate or to the reduced 5-formyl derivative. In contrast 5-methyltetrahydropteroylglutamate was much less stable nutritionally than expected.Unsubstituted tetrahydropteroylglutamate was most unstable nutritionally but in contrast to the other derivatives examined it was more stable under acidic than basic conditions. Ascorbate was found to be a far superior stabilizing agent than 2-mercaptoethanol at comparable concentrations."}
{"id": "PMID:236649", "title": "Pepsin output after disruption of the human gastric mucosal barrier by taurocholic acid.", "content": "Test solutions containing 10 mM taurocholic acid in 160 mM HCl were instilled into the stomachs of healthy volunteers to disrupt the gastric mucosal barrier. Although significant back diffusion of hydrogen ions and exsorption of sodium ions occurred, there was no significant increase in pepsin output compared to control studies with 160 mm HCl alone. Our data suggest that 160 mM HCl produces a many-fold increase in basal pepsin output. In the innervated stomach of man disruption of the gastric mucosal barrier by taurocholic acid in acid solution is not accompanied by increased pepsin secretion compared to that produced by 160 mM HCl alone.", "contents": "Pepsin output after disruption of the human gastric mucosal barrier by taurocholic acid. Test solutions containing 10 mM taurocholic acid in 160 mM HCl were instilled into the stomachs of healthy volunteers to disrupt the gastric mucosal barrier. Although significant back diffusion of hydrogen ions and exsorption of sodium ions occurred, there was no significant increase in pepsin output compared to control studies with 160 mm HCl alone. Our data suggest that 160 mM HCl produces a many-fold increase in basal pepsin output. In the innervated stomach of man disruption of the gastric mucosal barrier by taurocholic acid in acid solution is not accompanied by increased pepsin secretion compared to that produced by 160 mM HCl alone."}
{"id": "PMID:236650", "title": "Comparative study of secretin and Lundh tests.", "content": "Exocrine pancreatic function in 19 patients with pancreatic disease and in 14 of 16 controls was measured by secretin stimulation and by the Lundh test on two different occasions. Peak bicarbonate concentration in the Lundh test emerged as the most reliable parameters. No additional diagnostic value was obtained by measuring enzymes after secretin injection. In 6 patients with chronic and in 8 of 13 patients with acute pancreatitis, both tests gave results that agreed with each other. The remaining 5 patients showed either an abnormal secretin value or an abnormal Lundh test. This is consistent with the wide variation seen in acute pancreatitis. It is concluded that the Lundh test as well as the secretin test were of value in the assessment of chronic pancreatic disease. The secretin test may be slightly more sensitive to mild and acute pancreatic damage than is the Lundh test. However stimulation of the pancreas by a test meal is easier to perform and more economic.", "contents": "Comparative study of secretin and Lundh tests. Exocrine pancreatic function in 19 patients with pancreatic disease and in 14 of 16 controls was measured by secretin stimulation and by the Lundh test on two different occasions. Peak bicarbonate concentration in the Lundh test emerged as the most reliable parameters. No additional diagnostic value was obtained by measuring enzymes after secretin injection. In 6 patients with chronic and in 8 of 13 patients with acute pancreatitis, both tests gave results that agreed with each other. The remaining 5 patients showed either an abnormal secretin value or an abnormal Lundh test. This is consistent with the wide variation seen in acute pancreatitis. It is concluded that the Lundh test as well as the secretin test were of value in the assessment of chronic pancreatic disease. The secretin test may be slightly more sensitive to mild and acute pancreatic damage than is the Lundh test. However stimulation of the pancreas by a test meal is easier to perform and more economic."}
{"id": "PMID:236651", "title": "Pharmacology and clinical use of antacids.", "content": "The pharmacology of antacids, with particular reference to their clinical use in treating acid-peptic disease, is discussed.  Liquid antacid suspension should be given at least as often as one hour after each meal and at bedtime.  Inthe treatment of the acute phase of acid-peptic disease, hourly antacid is recommended.  The dose should be planned in terms of milliequivalents of acid neutralizing capacity and should be adjusted according to the type of disease under treatment.  All antacids have side effects, the most serious of which are metabolic.  In clinical terms, the harmful sustemicside effects of calcium carbonate and sodium bicarbonate outweigh their benefit as neutralizing agents; they should rarely be employed in the treatment of acid-peptic disease.  The more common antacid side effects of diarrhea (magnesium hydroxide) and constipation (aluminum hydroxide) are best managed by appropriately alternating the agents or by using one of the various antacid mixtures.", "contents": "Pharmacology and clinical use of antacids. The pharmacology of antacids, with particular reference to their clinical use in treating acid-peptic disease, is discussed.  Liquid antacid suspension should be given at least as often as one hour after each meal and at bedtime.  Inthe treatment of the acute phase of acid-peptic disease, hourly antacid is recommended.  The dose should be planned in terms of milliequivalents of acid neutralizing capacity and should be adjusted according to the type of disease under treatment.  All antacids have side effects, the most serious of which are metabolic.  In clinical terms, the harmful sustemicside effects of calcium carbonate and sodium bicarbonate outweigh their benefit as neutralizing agents; they should rarely be employed in the treatment of acid-peptic disease.  The more common antacid side effects of diarrhea (magnesium hydroxide) and constipation (aluminum hydroxide) are best managed by appropriately alternating the agents or by using one of the various antacid mixtures."}
{"id": "PMID:236652", "title": "Arterial blood gases and pH during sleep in chronic obstructive pulmonary disease.", "content": "Arterial blood gases were measured during 7 hours of sleep in 15 patients with severe stable chronic obstructive pulmonary discrease (COPD); 6 awake patients with COPD studies in recumbency for an average of 5 hours served as controls. Mean maximal decrease in arterial oxygen partial pressure (PaO2) (plus or minus SD) was 13.5 plus or minus 3.9 mm Hg for sleeping patients (p less than 0.005) and 5.5 plus or minus 1.7 mm Hg for controls (p less than 0.1), respectively. Changes in pH during sleep were of the magnitude expected with acute changes in arterial carbon dioxide partial pressure (PaCO2) in patients with chronic hypercapnia. Consistent changes in heart rate, respiratory frequency or cardiac rhythm were not observed during sleep. Nocturnal worsening of hypoxemia could be explained by alveolar hypoventilation in six sleeping patients and in five controls; in nine sleeping patients, further impariment of ventilation-perfusion mismatch also contributed to worsening of hypoxemia. There was no relationship between the decrease in PaO2 during sleep and the degree of airways obstruction or the PaO2 level when awake. Because of low PaO2, when awake, a fall in PaO2 during sleep brings values into the steep part of the oxyhemoglobin dissociation curve where slight changes in PaO2 result in marked changes in oxygen content. All patients with COPD whose waking PaO2 was below 60 mm Hg had PaO2 below 50 mm Hg during sleep; nocturnal oxygen therapy should be considered in such patients, particularly in the presence of polycythemia or troublesome right-sided heart failure.", "contents": "Arterial blood gases and pH during sleep in chronic obstructive pulmonary disease. Arterial blood gases were measured during 7 hours of sleep in 15 patients with severe stable chronic obstructive pulmonary discrease (COPD); 6 awake patients with COPD studies in recumbency for an average of 5 hours served as controls. Mean maximal decrease in arterial oxygen partial pressure (PaO2) (plus or minus SD) was 13.5 plus or minus 3.9 mm Hg for sleeping patients (p less than 0.005) and 5.5 plus or minus 1.7 mm Hg for controls (p less than 0.1), respectively. Changes in pH during sleep were of the magnitude expected with acute changes in arterial carbon dioxide partial pressure (PaCO2) in patients with chronic hypercapnia. Consistent changes in heart rate, respiratory frequency or cardiac rhythm were not observed during sleep. Nocturnal worsening of hypoxemia could be explained by alveolar hypoventilation in six sleeping patients and in five controls; in nine sleeping patients, further impariment of ventilation-perfusion mismatch also contributed to worsening of hypoxemia. There was no relationship between the decrease in PaO2 during sleep and the degree of airways obstruction or the PaO2 level when awake. Because of low PaO2, when awake, a fall in PaO2 during sleep brings values into the steep part of the oxyhemoglobin dissociation curve where slight changes in PaO2 result in marked changes in oxygen content. All patients with COPD whose waking PaO2 was below 60 mm Hg had PaO2 below 50 mm Hg during sleep; nocturnal oxygen therapy should be considered in such patients, particularly in the presence of polycythemia or troublesome right-sided heart failure."}
{"id": "PMID:236654", "title": "Perinatal infection and vaginal flora.", "content": "Vaginal cultures were obtained from 1, 083 mothers on admission to the labor floor. The additional bacteriologic information gained from this survey was not sufficient to warrant continued use of the admission vaginal culture as a screening procedure.", "contents": "Perinatal infection and vaginal flora. Vaginal cultures were obtained from 1, 083 mothers on admission to the labor floor. The additional bacteriologic information gained from this survey was not sufficient to warrant continued use of the admission vaginal culture as a screening procedure."}
{"id": "PMID:236655", "title": "Surface properties of the amniotic fluid in normal pregnancy.", "content": "The surface properties of the amniotic fluid were determined in 96 normal pregnancies between weeks 23 and 41. The y-max, y-min, hysteresis areaa, and stability index were used as parameters for evaluation of the surface tension are diagrams. These results were plotted against the gestation week and a curve for the normal course of surface tension of the amniotic fluid during the second half of gestation was obtained. The influence of addition of blood, vernix, and meconium to amniotic fluid as well as that of changes in the pH and dilution were examined. The results were unaffected by either blood, vernix, or pH changes. The slight scatter of the y-min values makes this parameter particularly suitable for determining fetal lung maturity.", "contents": "Surface properties of the amniotic fluid in normal pregnancy. The surface properties of the amniotic fluid were determined in 96 normal pregnancies between weeks 23 and 41. The y-max, y-min, hysteresis areaa, and stability index were used as parameters for evaluation of the surface tension are diagrams. These results were plotted against the gestation week and a curve for the normal course of surface tension of the amniotic fluid during the second half of gestation was obtained. The influence of addition of blood, vernix, and meconium to amniotic fluid as well as that of changes in the pH and dilution were examined. The results were unaffected by either blood, vernix, or pH changes. The slight scatter of the y-min values makes this parameter particularly suitable for determining fetal lung maturity."}
{"id": "PMID:236656", "title": "Placenta to lamb fetus transfusion in utero during acute hypoxia.", "content": "Maternal and fetal hemodynamics, placental blood flow, fetal-placental blood volume, placental blood volume, and fetal blood volumes were measured in six chronic sheep prepartions to evaluate their changes during acute fetal hypoxia induced by maternal hypoxia. During fetal hypoxia, the maternal and fetal arterial blood pressure and heart rate were essentially unchanged. The placental blood flow (control equal to 325 ml.per kilogram per minute) was also unchanged during the hypoxia period. However, the placental blood volume decreased significantly from 65 to 60 and 51 ml. per kilogram at 15 and 30 minutes of hypoxia period, respectively. The fetal blood volume increased reciprocally and significantly from 86 to 109 and 102 ml. per kilogram at the same periods of hypoxia since the fetal-placental blood volumes were unchanged. These blood volume changes persisted for 30 to 60 minutes following the stoppage of hypoxia experiments. The placental vascular resistance measured in six experiments showed a significant increment during hypoxia, suggesting placental vasoconstriction as the responsible mechanism for the reduction of placental blood volume and reciprocal increase in fetal blood volume. The data suggest that significant placental transfusion to the lamb fetus may occur in utero during fetal hypoxia resulting in a higher fetal blood volume before birth.", "contents": "Placenta to lamb fetus transfusion in utero during acute hypoxia. Maternal and fetal hemodynamics, placental blood flow, fetal-placental blood volume, placental blood volume, and fetal blood volumes were measured in six chronic sheep prepartions to evaluate their changes during acute fetal hypoxia induced by maternal hypoxia. During fetal hypoxia, the maternal and fetal arterial blood pressure and heart rate were essentially unchanged. The placental blood flow (control equal to 325 ml.per kilogram per minute) was also unchanged during the hypoxia period. However, the placental blood volume decreased significantly from 65 to 60 and 51 ml. per kilogram at 15 and 30 minutes of hypoxia period, respectively. The fetal blood volume increased reciprocally and significantly from 86 to 109 and 102 ml. per kilogram at the same periods of hypoxia since the fetal-placental blood volumes were unchanged. These blood volume changes persisted for 30 to 60 minutes following the stoppage of hypoxia experiments. The placental vascular resistance measured in six experiments showed a significant increment during hypoxia, suggesting placental vasoconstriction as the responsible mechanism for the reduction of placental blood volume and reciprocal increase in fetal blood volume. The data suggest that significant placental transfusion to the lamb fetus may occur in utero during fetal hypoxia resulting in a higher fetal blood volume before birth."}
{"id": "PMID:236657", "title": "Non-contact tonometry by assistants.", "content": "The ability of assistants to screen for elevated intraocular pressure (IOP) with the non-contact tonometer was evaluated. They had ten minutes of instruction with the instrument prior to the study. The estimates by the assistants correlated highly with those of the optometrists. The patients' responses were favorable. It follows from this study that an assistant with minimal training can reliably perform IOP screening with the non-contact tonometer under the supervision of an optometrist.", "contents": "Non-contact tonometry by assistants. The ability of assistants to screen for elevated intraocular pressure (IOP) with the non-contact tonometer was evaluated. They had ten minutes of instruction with the instrument prior to the study. The estimates by the assistants correlated highly with those of the optometrists. The patients' responses were favorable. It follows from this study that an assistant with minimal training can reliably perform IOP screening with the non-contact tonometer under the supervision of an optometrist."}
{"id": "PMID:236658", "title": "Tissue culture of bone marrow. V. Effect of 5Beta(H) steroids and cyclic AMP on heme synthesis.", "content": "In mice 5beta(H) steroids have been shown tostimulate heme synthesis in vivo. The current studies were undertaken to evaluate the effect of these steroids on heme synthesis by use of the \"well\" method of marrow culture. The 5beta(H) steroid metabolites 3alpha-hydroxy-5beta-pregnane-11, 20-dione, 3beta-hydroxy-5beta-pregnan-20-one, 3 alpha,17alpha-dihydroxy-5beta-androstan-3-one stimulated Fe uptake by human marrow explants cultured in wells. The dibutyrl analog of adenosine 3',5'-monophosphate (db cAMP) also stimulated Fe uptake. The effect of the latter compound was enhanced by theophylline. There was no additive nor synergistic effect between db cAMP and the 5beta(H) steroid metabolites. There was no inhibition of the steroid metabolite effect by either antierythropoietin serum or cyproterone. Uptake of fe was also enhanced by the cations Ca++ and Co++.", "contents": "Tissue culture of bone marrow. V. Effect of 5Beta(H) steroids and cyclic AMP on heme synthesis. In mice 5beta(H) steroids have been shown tostimulate heme synthesis in vivo. The current studies were undertaken to evaluate the effect of these steroids on heme synthesis by use of the \"well\" method of marrow culture. The 5beta(H) steroid metabolites 3alpha-hydroxy-5beta-pregnane-11, 20-dione, 3beta-hydroxy-5beta-pregnan-20-one, 3 alpha,17alpha-dihydroxy-5beta-androstan-3-one stimulated Fe uptake by human marrow explants cultured in wells. The dibutyrl analog of adenosine 3',5'-monophosphate (db cAMP) also stimulated Fe uptake. The effect of the latter compound was enhanced by theophylline. There was no additive nor synergistic effect between db cAMP and the 5beta(H) steroid metabolites. There was no inhibition of the steroid metabolite effect by either antierythropoietin serum or cyproterone. Uptake of fe was also enhanced by the cations Ca++ and Co++."}
{"id": "PMID:236659", "title": "Hydrocortisone restoration of the pH-dependent metabolic responses to catecholamines.", "content": "Feeding NH4CL to fasted rats caused changes of blood levels of lactate, glycerol, and insulin, hepatic levels of glycogen and phosphorylase, and muscle levels of glycogen and glucose 6-P in the direction opposite to the changes induced by respiratory alkalosis. The effects of epinephrine and isoproterenol in vivo on these metabolic indices, which are classified as their function mediated via the adrenegic beta receptor, were potentiated by NH4CL feeding in contrast to their attenuation in alkalosis. The prior treatment of the rat with hydrocortisone was very effective in overcoming the alkalosis-induced inhibition of the beta-receptor-mediated metabolic actions of epinephrine and isoproterenol, such as the activation of liver phosphorylase, accumulation of muscle hexose phosphates, and stimulation of pancreatic secretion of insulin. Epinephrine sensitivity of the liver and muscle levels of cyclic AMP was not altered by the hydrocortisone therapy or inductions of alkalosis and acidosis. The mechanism for the hydrocortisone restoration of the adrenergic beta functions in alkalosis is discussed as related to its permissive effect.", "contents": "Hydrocortisone restoration of the pH-dependent metabolic responses to catecholamines. Feeding NH4CL to fasted rats caused changes of blood levels of lactate, glycerol, and insulin, hepatic levels of glycogen and phosphorylase, and muscle levels of glycogen and glucose 6-P in the direction opposite to the changes induced by respiratory alkalosis. The effects of epinephrine and isoproterenol in vivo on these metabolic indices, which are classified as their function mediated via the adrenegic beta receptor, were potentiated by NH4CL feeding in contrast to their attenuation in alkalosis. The prior treatment of the rat with hydrocortisone was very effective in overcoming the alkalosis-induced inhibition of the beta-receptor-mediated metabolic actions of epinephrine and isoproterenol, such as the activation of liver phosphorylase, accumulation of muscle hexose phosphates, and stimulation of pancreatic secretion of insulin. Epinephrine sensitivity of the liver and muscle levels of cyclic AMP was not altered by the hydrocortisone therapy or inductions of alkalosis and acidosis. The mechanism for the hydrocortisone restoration of the adrenergic beta functions in alkalosis is discussed as related to its permissive effect."}
{"id": "PMID:236660", "title": "Inotropic and intracellular acid-base changes during metabolic acidosis.", "content": "Experiments in isolated, Ringer-perfused isovolumic rabbit hearts showed that metabolic acidosis resulted in a decrease in peak left ventricular pressure and dP/dt. Concomitantly, the decrease in extracellular pH from 7.28 plus or minus 0.02 to 6.82 plus or minus 0.02 at constant PaCO2 was associated with a negative av HCO3- difference that lasted throughout the duration of acidosis. This negative av HCO3- difference indicated that either HCO3- moved into the intravascular space or H+ moved in the opposite direction during acidosis. During perfusion with normal pH solution av HCO3- was not significantly different from zero. Washout of the extracellular space with the acid solution can account for only 32 percent of the total amount of HCO3-recovered in the venous perfusate during the 30 min of acidosis. The remaining 68 percent (10.7 plus or minus 3.1 mmol times kg-1 of cardiac tissue) must then have originated in the cellular fluid. When intracellular fluid volume is taken into account, it can be calculated that 21.3 plus or minus 6.1 mmol of HCO3- moved into the vascular space per liter of intracellular water. The magnitude of this HCO3- flux suggests that significant myocardial cellular acid-base changes are associated with metabolic acidosis.", "contents": "Inotropic and intracellular acid-base changes during metabolic acidosis. Experiments in isolated, Ringer-perfused isovolumic rabbit hearts showed that metabolic acidosis resulted in a decrease in peak left ventricular pressure and dP/dt. Concomitantly, the decrease in extracellular pH from 7.28 plus or minus 0.02 to 6.82 plus or minus 0.02 at constant PaCO2 was associated with a negative av HCO3- difference that lasted throughout the duration of acidosis. This negative av HCO3- difference indicated that either HCO3- moved into the intravascular space or H+ moved in the opposite direction during acidosis. During perfusion with normal pH solution av HCO3- was not significantly different from zero. Washout of the extracellular space with the acid solution can account for only 32 percent of the total amount of HCO3-recovered in the venous perfusate during the 30 min of acidosis. The remaining 68 percent (10.7 plus or minus 3.1 mmol times kg-1 of cardiac tissue) must then have originated in the cellular fluid. When intracellular fluid volume is taken into account, it can be calculated that 21.3 plus or minus 6.1 mmol of HCO3- moved into the vascular space per liter of intracellular water. The magnitude of this HCO3- flux suggests that significant myocardial cellular acid-base changes are associated with metabolic acidosis."}
{"id": "PMID:236661", "title": "Ileal HCO3 secretion: relationship to Na and Cl transport and effect of theophylline.", "content": "Interrelationships among Na, Cl, and HCO3 transport processes were examined in short-circuited rabbit ileal mucosa. As serosal (HCO3) was increased from 10 to 50 mM (pH from 7.1 to 7.8), net Na absorption decreased from 4.6 to 0.3 mueq/h-cm2, net Cl flux changed from absorption of 0.9 to secretion of 0.9 and a net HCO3 secretion of 3.0 developed. A similar change in net Cl flux was also observed when serosal Pco2 was altered at constant (HCO3). In Cl-free SO4-Ringer, serosal alkalinization produced net HCO3 secretion which was not significantly less than that observed in Cl-containing Ringer. Theophylline caused secretory changes in net Na and Cl fluxes at both 10 and 50 mM serosal (HCO3). Theophylline did not alter net HCO3 flux in Cl-Ringer but increased net HCO3 flux in SO4-Ringer. Total dc conductance was decreased by both serosal alkalinization and theophylline. Shortcircuit current was consistently increased by theophylline but not by serosal alkalinization. The results indicate that ileal ion transport is regulated in part by serosal pH and/or (HCO3) and that resulting changes in Cl and HCO3 transport are coupled one-for-one with changes in Na transport. Furthermore, HCO3 secretion does not require the presence of Cl in the bathing medium.", "contents": "Ileal HCO3 secretion: relationship to Na and Cl transport and effect of theophylline. Interrelationships among Na, Cl, and HCO3 transport processes were examined in short-circuited rabbit ileal mucosa. As serosal (HCO3) was increased from 10 to 50 mM (pH from 7.1 to 7.8), net Na absorption decreased from 4.6 to 0.3 mueq/h-cm2, net Cl flux changed from absorption of 0.9 to secretion of 0.9 and a net HCO3 secretion of 3.0 developed. A similar change in net Cl flux was also observed when serosal Pco2 was altered at constant (HCO3). In Cl-free SO4-Ringer, serosal alkalinization produced net HCO3 secretion which was not significantly less than that observed in Cl-containing Ringer. Theophylline caused secretory changes in net Na and Cl fluxes at both 10 and 50 mM serosal (HCO3). Theophylline did not alter net HCO3 flux in Cl-Ringer but increased net HCO3 flux in SO4-Ringer. Total dc conductance was decreased by both serosal alkalinization and theophylline. Shortcircuit current was consistently increased by theophylline but not by serosal alkalinization. The results indicate that ileal ion transport is regulated in part by serosal pH and/or (HCO3) and that resulting changes in Cl and HCO3 transport are coupled one-for-one with changes in Na transport. Furthermore, HCO3 secretion does not require the presence of Cl in the bathing medium."}
{"id": "PMID:236662", "title": "Tetany: quantitative interrelationships between calcium and alkalosis.", "content": "Tetany occurs with hypocalcemia and alkalosis or both. The interrelationship of calcium and acid-base balance necessary for inducing tetany, the role of the central nervous system, and the rate of development of hypocalcemia have been investigated. Tetany occurred in less than 50 percent of one group of dogs made alkalotic by hyperventilation or made hypocalcemic by infusion of ethylene glycol-bis(beta-amino ethyl ether) N, N'-tetraacetate. In contrast, hypocalcemia combined with hypocapnic alkalosis always produced tetany. Slowly evolving hypocalcemia was achieved inanother group of dogs by thyroparathyroidectomy, and tetany was induced postoperatively by hypocapnic alkalosis. An identical relationship between serum calcium ion concentration and arterial pH or CO2 tension was found in both groups. Tetany could not be related to the cerebrospinal fluid (CSF) calcium ion content in either group. Hypocalcemia and alkalosis are therefore coparticipants in the development of tetany and are independent of the rate of development of hypocalcemia and of CSF calcium ion concentration. The importance of alkalosis in tetany with hypoparathyroidism is emphasized.", "contents": "Tetany: quantitative interrelationships between calcium and alkalosis. Tetany occurs with hypocalcemia and alkalosis or both. The interrelationship of calcium and acid-base balance necessary for inducing tetany, the role of the central nervous system, and the rate of development of hypocalcemia have been investigated. Tetany occurred in less than 50 percent of one group of dogs made alkalotic by hyperventilation or made hypocalcemic by infusion of ethylene glycol-bis(beta-amino ethyl ether) N, N'-tetraacetate. In contrast, hypocalcemia combined with hypocapnic alkalosis always produced tetany. Slowly evolving hypocalcemia was achieved inanother group of dogs by thyroparathyroidectomy, and tetany was induced postoperatively by hypocapnic alkalosis. An identical relationship between serum calcium ion concentration and arterial pH or CO2 tension was found in both groups. Tetany could not be related to the cerebrospinal fluid (CSF) calcium ion content in either group. Hypocalcemia and alkalosis are therefore coparticipants in the development of tetany and are independent of the rate of development of hypocalcemia and of CSF calcium ion concentration. The importance of alkalosis in tetany with hypoparathyroidism is emphasized."}
{"id": "PMID:236663", "title": "Distribution of H+ and HCO3 minus between CSF and blood during metabolic acidosis in dogs.", "content": "To determine whether the regulation of brain extracellular fluid acid-base balance is by active ion transport or passive distribution, changes in cisternal and lumbar cerebrospinal fluid (CSF) (H+) and (HCO3 minus) were assessed in five dogs with normal acid-base status and in six dogs during metabolic acidosis. Both groups were mechanically ventilated to maintain a constant PaCO2. The pH, PCO2, (HCO3 minus), and (lactate) in CSF and arterial plasma and the CSF/plasma DC potential difference were determined at intervals, and the electrochemical potential differnces (mu) for H+ and HCO3 minus were calculated. Following control measurements at pHa equal to 7.40, metabolic acidosis was induced by infusion of 0.6 N HCl. Measurements were made 0, 3, 4.5, and 6 h thereafter and at 0, 3, and 6 h in the control series. A steady state for ion distribution was reached by 4.5 h. In the control series at 6 h the values of mu for H+ and HCO3 minus were within minus 0.2 and +0.5 mV of initial values at the cistern and +0.1 and +0.9 mV at the lumbar site. During metabolic acidosis, the 6-h values at the cistern returned to 0.0 and +0.7 mV of control for muH+ and muHCO3 minus while lumbar values returned to +0.5 and minus 0.4 mV. The closeness of these 6-h values of mu to control is compatible with passive distribution of H+ and HCO3 minus between CSF and blood.", "contents": "Distribution of H+ and HCO3 minus between CSF and blood during metabolic acidosis in dogs. To determine whether the regulation of brain extracellular fluid acid-base balance is by active ion transport or passive distribution, changes in cisternal and lumbar cerebrospinal fluid (CSF) (H+) and (HCO3 minus) were assessed in five dogs with normal acid-base status and in six dogs during metabolic acidosis. Both groups were mechanically ventilated to maintain a constant PaCO2. The pH, PCO2, (HCO3 minus), and (lactate) in CSF and arterial plasma and the CSF/plasma DC potential difference were determined at intervals, and the electrochemical potential differnces (mu) for H+ and HCO3 minus were calculated. Following control measurements at pHa equal to 7.40, metabolic acidosis was induced by infusion of 0.6 N HCl. Measurements were made 0, 3, 4.5, and 6 h thereafter and at 0, 3, and 6 h in the control series. A steady state for ion distribution was reached by 4.5 h. In the control series at 6 h the values of mu for H+ and HCO3 minus were within minus 0.2 and +0.5 mV of initial values at the cistern and +0.1 and +0.9 mV at the lumbar site. During metabolic acidosis, the 6-h values at the cistern returned to 0.0 and +0.7 mV of control for muH+ and muHCO3 minus while lumbar values returned to +0.5 and minus 0.4 mV. The closeness of these 6-h values of mu to control is compatible with passive distribution of H+ and HCO3 minus between CSF and blood."}
{"id": "PMID:236664", "title": "Distribution of H+ and HCO3 minus between CSF and blood during respiratory acidosis in dogs.", "content": "To evaluate the regulation of (H+) and (HCO3 minus) in brain extracellular fluid during respiratory acidosis, the changes in cisternal and lumbar CSF acid-base state were assessed in six anteshetized, paralyzed, mechanically ventilated dogs rendered hypercapnic by increase in FIco2. Arterial (HCO3 minus) was held constant. The electrochemical potential difference (mu) between CSF and blood for H+ and HCO3 minus was calculated from values for (H+) and (HCO3 minus) in CSF and arterial plasma and the simultaneously measured CSF/plasma DC potential difference. Measurements were made at pHa equal to 7.40, after stable arterial values of pHa of about 7.2 were attained and 3, 4.5, and 6 h thereafter. A steady state for ion distribution was attained by 4.5 h. Values of mu for H+ and HCO3 minus at 6 h had returned to +0.7 and minus 0.7 mV of control for cisternal CSF and +1.3 and minus 0.6 mV of control for lumbar CSF. The attainment of steady-state values for mu close to control is comparable with passive distribution of these ions between CSF and blood.", "contents": "Distribution of H+ and HCO3 minus between CSF and blood during respiratory acidosis in dogs. To evaluate the regulation of (H+) and (HCO3 minus) in brain extracellular fluid during respiratory acidosis, the changes in cisternal and lumbar CSF acid-base state were assessed in six anteshetized, paralyzed, mechanically ventilated dogs rendered hypercapnic by increase in FIco2. Arterial (HCO3 minus) was held constant. The electrochemical potential difference (mu) between CSF and blood for H+ and HCO3 minus was calculated from values for (H+) and (HCO3 minus) in CSF and arterial plasma and the simultaneously measured CSF/plasma DC potential difference. Measurements were made at pHa equal to 7.40, after stable arterial values of pHa of about 7.2 were attained and 3, 4.5, and 6 h thereafter. A steady state for ion distribution was attained by 4.5 h. Values of mu for H+ and HCO3 minus at 6 h had returned to +0.7 and minus 0.7 mV of control for cisternal CSF and +1.3 and minus 0.6 mV of control for lumbar CSF. The attainment of steady-state values for mu close to control is comparable with passive distribution of these ions between CSF and blood."}
{"id": "PMID:236665", "title": "Distribution of H+ and HCO3 minus between CSF and blood during respiratory alkalosis in dogs.", "content": "Anesthetized, paralyzed dogs after a control period at normal pHa were hyperventilated to produce a hypocapnic alkalosis. The pH, PCO2, (HCO3 minus), and (lactate) in cisternal and lumbar CSF and arterial blood were determined at normal conditions (control) shortly after induction of respiratory alkalosis (time 0) and 3, 4.5, and 6 h thereafter. These values along with measurements of the CSF/plasma DC potential (E) allowed calculations of the electrochemical potential difference (mu) between CSF and blood for H+ and HCO3 minus. After 6 h of hypocapnic alkalosis, muH+ and muHCO3 minus had returned to minus 0.7 and minus 1.0 mV of control at the cistern and to minus 1.0 and +0.4 mV of control for lumbar CSF. This return of mu is compatible with a passive distribution of these ions though active ion regulation is not ruled out. Assuming passive distribution, differences in deltaE/DELTApHa between metabolic and respiratory acid-base changes determined the extent of CSF pH homeostasis during compensated acid-base derangements.", "contents": "Distribution of H+ and HCO3 minus between CSF and blood during respiratory alkalosis in dogs. Anesthetized, paralyzed dogs after a control period at normal pHa were hyperventilated to produce a hypocapnic alkalosis. The pH, PCO2, (HCO3 minus), and (lactate) in cisternal and lumbar CSF and arterial blood were determined at normal conditions (control) shortly after induction of respiratory alkalosis (time 0) and 3, 4.5, and 6 h thereafter. These values along with measurements of the CSF/plasma DC potential (E) allowed calculations of the electrochemical potential difference (mu) between CSF and blood for H+ and HCO3 minus. After 6 h of hypocapnic alkalosis, muH+ and muHCO3 minus had returned to minus 0.7 and minus 1.0 mV of control at the cistern and to minus 1.0 and +0.4 mV of control for lumbar CSF. This return of mu is compatible with a passive distribution of these ions though active ion regulation is not ruled out. Assuming passive distribution, differences in deltaE/DELTApHa between metabolic and respiratory acid-base changes determined the extent of CSF pH homeostasis during compensated acid-base derangements."}
{"id": "PMID:236666", "title": "Ion transport across the excised bullfrog lung.", "content": "Fluxes of ions and water across the short-circuited, excised bullfrog lung were determined by radioisotope techniques. The unidirectional flows of Na+, K+, Ca++, TcO4 minus, HCO3 minus, gluconate, rho-aminohippurate, dinitrophenolate, SO4 equal to, and water were symmetrical. Both HCO3 minus fluxes were reduced by acetazolamide. In contrast, Cl minus, Br minus I minus, and SCN minus movement from serosa to mucosa exceeded the flux in the opposite direction. Net Cl minus transport followed the kinetics of a saturable process and was inhibited by dinitrophenol and hypoxia. These results indicate an active secretion of halide anions and SCN minus into the lumen. Attempts to demonstrate Br minus anatagonism of Cl minus transport were equivocal. Cl minus transport accounted for 50 percent minus of the early short-circuit current but after 90 min the two measurements were equal. Incubation of the lung in bicarbonate-free Ringer revealed unequal decreases in the H+ concentration of the bathing solutions. Net \"base\" addition to the serosal solution was reduced by prior removal of the blood from the pulmonary vasculature. Therefore, \"base\" release could not be localized to the epithelia. The Na+, K+, Ca++ and Cl minus composition of the lung tissue was unchanged over 3 h. Since tissue and, hence cell Cl minus is lower than the concentration in the bathing solution the Cl pump is probably located in the luminal border of the alveolar epithelial cell.", "contents": "Ion transport across the excised bullfrog lung. Fluxes of ions and water across the short-circuited, excised bullfrog lung were determined by radioisotope techniques. The unidirectional flows of Na+, K+, Ca++, TcO4 minus, HCO3 minus, gluconate, rho-aminohippurate, dinitrophenolate, SO4 equal to, and water were symmetrical. Both HCO3 minus fluxes were reduced by acetazolamide. In contrast, Cl minus, Br minus I minus, and SCN minus movement from serosa to mucosa exceeded the flux in the opposite direction. Net Cl minus transport followed the kinetics of a saturable process and was inhibited by dinitrophenol and hypoxia. These results indicate an active secretion of halide anions and SCN minus into the lumen. Attempts to demonstrate Br minus anatagonism of Cl minus transport were equivocal. Cl minus transport accounted for 50 percent minus of the early short-circuit current but after 90 min the two measurements were equal. Incubation of the lung in bicarbonate-free Ringer revealed unequal decreases in the H+ concentration of the bathing solutions. Net \"base\" addition to the serosal solution was reduced by prior removal of the blood from the pulmonary vasculature. Therefore, \"base\" release could not be localized to the epithelia. The Na+, K+, Ca++ and Cl minus composition of the lung tissue was unchanged over 3 h. Since tissue and, hence cell Cl minus is lower than the concentration in the bathing solution the Cl pump is probably located in the luminal border of the alveolar epithelial cell."}
{"id": "PMID:236667", "title": "Effects of physical training on cardiac myosin ATPase activity.", "content": "Cardiac myosin from rats exercised 90 or 150 min daily for 8 wk was compared with the myosin from the hearts of matched sedentary controls. The Ca++-ATPase activity was increased 17 percent in rats exercised 90 min and 30 percent in rats exercised 150 min daily. In the exercised group 0.18 M KCl increased the myosin ATPase activity by 50 percent but had no effect in the control group. Ethylene glycol activated the Ca++-ATPase in control myosin preparations, but had no significant effect on myosin from conditioned hearts. Heavy meromyosin (HMM) from conditioned hearts had a higher Ca++-ATPase activity than from controls. Fluorescence with 8-anilinonaphthalene sulfonate (ANS) was increased 30 percent in HMM from conditioned hearts. The results suggest that the increased myosin ATPase activity in the hearts of exercised animals may be due to a local conformational change at or near the active site.", "contents": "Effects of physical training on cardiac myosin ATPase activity. Cardiac myosin from rats exercised 90 or 150 min daily for 8 wk was compared with the myosin from the hearts of matched sedentary controls. The Ca++-ATPase activity was increased 17 percent in rats exercised 90 min and 30 percent in rats exercised 150 min daily. In the exercised group 0.18 M KCl increased the myosin ATPase activity by 50 percent but had no effect in the control group. Ethylene glycol activated the Ca++-ATPase in control myosin preparations, but had no significant effect on myosin from conditioned hearts. Heavy meromyosin (HMM) from conditioned hearts had a higher Ca++-ATPase activity than from controls. Fluorescence with 8-anilinonaphthalene sulfonate (ANS) was increased 30 percent in HMM from conditioned hearts. The results suggest that the increased myosin ATPase activity in the hearts of exercised animals may be due to a local conformational change at or near the active site."}
{"id": "PMID:236668", "title": "Ion transport by amphibian antrum in vitro. I. General characteristics.", "content": "Both Necturus and bullfrog antrum show stable PD, resistance, and short-circuit current (Isc) when mounted in an Ussing chamber. Measurements of Na+ and Cl minus flux showed that both ions are actively transported across Necturus antrum, Na+ from secretory to nutrient, Cl minus from nutrient to secretory (both net fluxes being similar to 0.30 mueq cm minus 2 h minus 1). Only the Na+ transport contributed to the Isc and PD as evidenced by a) Na+ removal, b) the effects of amiloride on the secretory surface, c) the effects of ouabain on the nutrient side. Microelectrode experiments confirm the Na+ conductance of the secretory cell membrance, a HCO3 minus conductance of both cell membranes, and a KCl conductance across the nutrient cell membrane. In addition, antrum apparently secretes alkali (similar to 0.35 mueq cm minus 2 h minus 1), which secretion is sensitive to metabolic inhibitors and Diamox. Nutrientside HCO3 minus increased the rate of alkaline secretion and a transmucosal HCO3 minus gradient could contribute to ISC and PD. A model is proposed to account for the electrical properties of the tissue.", "contents": "Ion transport by amphibian antrum in vitro. I. General characteristics. Both Necturus and bullfrog antrum show stable PD, resistance, and short-circuit current (Isc) when mounted in an Ussing chamber. Measurements of Na+ and Cl minus flux showed that both ions are actively transported across Necturus antrum, Na+ from secretory to nutrient, Cl minus from nutrient to secretory (both net fluxes being similar to 0.30 mueq cm minus 2 h minus 1). Only the Na+ transport contributed to the Isc and PD as evidenced by a) Na+ removal, b) the effects of amiloride on the secretory surface, c) the effects of ouabain on the nutrient side. Microelectrode experiments confirm the Na+ conductance of the secretory cell membrance, a HCO3 minus conductance of both cell membranes, and a KCl conductance across the nutrient cell membrane. In addition, antrum apparently secretes alkali (similar to 0.35 mueq cm minus 2 h minus 1), which secretion is sensitive to metabolic inhibitors and Diamox. Nutrientside HCO3 minus increased the rate of alkaline secretion and a transmucosal HCO3 minus gradient could contribute to ISC and PD. A model is proposed to account for the electrical properties of the tissue."}
{"id": "PMID:236669", "title": "Pulmonary effects of paraquat in the first day after injection.", "content": "To learn whether surface force changes precede the appearance of lung edema during experimental intoxication due to paraquat, we studied rats for 1 day following injection of 27 mg/kg iv. By 24 h, surface-active material recovered by lung lavage was decreased 32 percent, and changes in lung microsections and recoil pressure at half-deflation suggested decreased alveolar stability. Despite a 25 percent loss in overall body weight, lung weight increased more than 7 percent and protein concentration in lung lavage fluid increased by 158 percent. Lung edema was demonstrated morphologically as early as we could detect changes in surfactant or lung mechanical properties. Metabolic studies with lung tissue slices incubated with 4.5 times 10-4 M paraquat showed a fourfold increase in 14CO2 formed from (1-14C) glucose, but no significant change in 14CO2 form (6-14C) glucose, suggesting increased utilization of the pentose pathway for oxidation of glucose. (1-14C) Acetate oxidation was impaired slightly, but incorporation into lipid was decreased by 70 percent. we conclude that paraquat intoxication in the rat is not a suitable model for studying uncomplicated perturbation of the surfactant system.", "contents": "Pulmonary effects of paraquat in the first day after injection. To learn whether surface force changes precede the appearance of lung edema during experimental intoxication due to paraquat, we studied rats for 1 day following injection of 27 mg/kg iv. By 24 h, surface-active material recovered by lung lavage was decreased 32 percent, and changes in lung microsections and recoil pressure at half-deflation suggested decreased alveolar stability. Despite a 25 percent loss in overall body weight, lung weight increased more than 7 percent and protein concentration in lung lavage fluid increased by 158 percent. Lung edema was demonstrated morphologically as early as we could detect changes in surfactant or lung mechanical properties. Metabolic studies with lung tissue slices incubated with 4.5 times 10-4 M paraquat showed a fourfold increase in 14CO2 formed from (1-14C) glucose, but no significant change in 14CO2 form (6-14C) glucose, suggesting increased utilization of the pentose pathway for oxidation of glucose. (1-14C) Acetate oxidation was impaired slightly, but incorporation into lipid was decreased by 70 percent. we conclude that paraquat intoxication in the rat is not a suitable model for studying uncomplicated perturbation of the surfactant system."}
{"id": "PMID:236670", "title": "Calcium and angiotensin tachyphylaxis in rat uterine smooth muscle.", "content": "Studies were carried out to investigate the relationship between extracellular Ca++ and the ability of a particular smooth muscle to develop tachyphylaxis to angiotensin II (AII). Stimulation of rat uterus by AII was found to be dependent on extracellular Ca++. Placing the tissue in 0 Ca++ completely blocked AII-induced contractions as did the presence of the \"Ca++ antagonists\" verapamil (10- minus 5M), SKF 525-A (10- MINUS 5M), tetracaine (10- minus 4M), Mn++ (8 times 10- minus 3M), or La-3+ (10- minus 3M). In addition, it is no longer possible to produce tachyphylaxis to AII in deplorazed rat uterus under conditions of pH and Ca++ concentration in which a normally polarized preparation would be unresponsive. Verapamil, on the other hand, was an even more effective antagonist of AII in depolarized preparations (ID50 of 10- minus 8M) than in normal tissues (ID50 of 2.0 times 10- minus 7M). Like the rat uterus, the smooth muscle of the guinea pig ileum also develops tachyphylaxis to AII, and the effect of this peptide was also blocked by 10- minus 5 M verapamil. Rabbit aorta, however, was found to be relatively resistant to both development of tachyphylaxis under conditions of low Ca++ and low pH and also to inhibition by even very high concentrations of verapamil (10- minus 4M). The results of these studies suggest that the Ca++ site involved in the tachyphylactic response to AII may be a physiologically important one in those smooth muscles in which movement of extracellular Ca++ contributes to the inward ion currents during excitation. Verapamil, however, appears to act at a common step in the excitation-contraction sequence in rat uterus. A working model of the interaction of AII with rat uterine smooth muscle is presented.", "contents": "Calcium and angiotensin tachyphylaxis in rat uterine smooth muscle. Studies were carried out to investigate the relationship between extracellular Ca++ and the ability of a particular smooth muscle to develop tachyphylaxis to angiotensin II (AII). Stimulation of rat uterus by AII was found to be dependent on extracellular Ca++. Placing the tissue in 0 Ca++ completely blocked AII-induced contractions as did the presence of the \"Ca++ antagonists\" verapamil (10- minus 5M), SKF 525-A (10- MINUS 5M), tetracaine (10- minus 4M), Mn++ (8 times 10- minus 3M), or La-3+ (10- minus 3M). In addition, it is no longer possible to produce tachyphylaxis to AII in deplorazed rat uterus under conditions of pH and Ca++ concentration in which a normally polarized preparation would be unresponsive. Verapamil, on the other hand, was an even more effective antagonist of AII in depolarized preparations (ID50 of 10- minus 8M) than in normal tissues (ID50 of 2.0 times 10- minus 7M). Like the rat uterus, the smooth muscle of the guinea pig ileum also develops tachyphylaxis to AII, and the effect of this peptide was also blocked by 10- minus 5 M verapamil. Rabbit aorta, however, was found to be relatively resistant to both development of tachyphylaxis under conditions of low Ca++ and low pH and also to inhibition by even very high concentrations of verapamil (10- minus 4M). The results of these studies suggest that the Ca++ site involved in the tachyphylactic response to AII may be a physiologically important one in those smooth muscles in which movement of extracellular Ca++ contributes to the inward ion currents during excitation. Verapamil, however, appears to act at a common step in the excitation-contraction sequence in rat uterus. A working model of the interaction of AII with rat uterine smooth muscle is presented."}
{"id": "PMID:236672", "title": "Uteroplacental blood flow during alkalosis in the sheep.", "content": "Uteroplacental blood flow was measured by the radioactive-microsphere technique in eight near-term pregnant ewes during a normal control period and during maternal metabolic alkalosis. All measurements were made on awake, unanesthetized animals. Alkalosis, defined for this study as an arterial pH of 7.60 or greater, was produced by the oral administration of sodium bicarbonate, 3 g/kg body wt. The rise in pH thus produced was unaccompanied by significant changes in systemic arterial blood pressure and cardiac output, while maternal arterial Pco2 rose slightly from control levels. Cotyledonary blood flow declined from a control value of 1,177 ml/min to 1,025 ml/min during alkalosis. This decline of 13 percent in cotyledonary blood flow is significant (P smaller than 0.002). Blood flow to the remaining uterine tissue, or noncotyledonary uterus, did not change with alkalosis, being maintained at approximately 195 ml/min. It is concluded that maternal alkalosis, unaccompained by major changes in Pco2 and systemic arterial pressure, causes a small increase in the resistance of the uteroplacental circulation.", "contents": "Uteroplacental blood flow during alkalosis in the sheep. Uteroplacental blood flow was measured by the radioactive-microsphere technique in eight near-term pregnant ewes during a normal control period and during maternal metabolic alkalosis. All measurements were made on awake, unanesthetized animals. Alkalosis, defined for this study as an arterial pH of 7.60 or greater, was produced by the oral administration of sodium bicarbonate, 3 g/kg body wt. The rise in pH thus produced was unaccompanied by significant changes in systemic arterial blood pressure and cardiac output, while maternal arterial Pco2 rose slightly from control levels. Cotyledonary blood flow declined from a control value of 1,177 ml/min to 1,025 ml/min during alkalosis. This decline of 13 percent in cotyledonary blood flow is significant (P smaller than 0.002). Blood flow to the remaining uterine tissue, or noncotyledonary uterus, did not change with alkalosis, being maintained at approximately 195 ml/min. It is concluded that maternal alkalosis, unaccompained by major changes in Pco2 and systemic arterial pressure, causes a small increase in the resistance of the uteroplacental circulation."}
{"id": "PMID:236673", "title": "Bicarbonate and sodium reabsorption by the isolated perfused kidney.", "content": "The role of bicarbonate reabsorption and of transtubular chloride gradients in the bulk reabsorption of sodium and water by renal tubules can be tested in the isolated perfused kidney by perfusing with a medium from which bicarbonate has been omitted. Perfusion of the isolated rat kidney with an artificial medium in which bicarbonate is replaced by chloride results in a fall in fractional reabsorption of sodium from 97 to 84%. Stepwise restoration of bicarbonate concentration in the perfusion medium to 25 meq/liter is associated with a parallel recovery of sodium reabsorption to control levels. Inhibition of bicarbonate reabsorption with acetazolamide produces a slightly smaller reduction in sodium reabsorption (97-89%), an effect not seen in the absence of bicarbonate. Acetazolamide greatly increases phosphate excretion and free water clearance in a way consistent with suppression of proximal tubular reabsorption. By contrast, simple omission of bicarbonate from the perfusing medium does not alter phosphaturia or free water clearance. Reabsorption of bicarbonate appears to account for a fraction of sodium reabsorption roughly equivalent to the proportion of sodium associated stoichiometrically with bicarbonate in the glomerule filtrate. The data do not support the hypothesis that the development of a transtubular chloride gradient is critically important for the reabsorption of a large fraction of the glomerular filtrate.", "contents": "Bicarbonate and sodium reabsorption by the isolated perfused kidney. The role of bicarbonate reabsorption and of transtubular chloride gradients in the bulk reabsorption of sodium and water by renal tubules can be tested in the isolated perfused kidney by perfusing with a medium from which bicarbonate has been omitted. Perfusion of the isolated rat kidney with an artificial medium in which bicarbonate is replaced by chloride results in a fall in fractional reabsorption of sodium from 97 to 84%. Stepwise restoration of bicarbonate concentration in the perfusion medium to 25 meq/liter is associated with a parallel recovery of sodium reabsorption to control levels. Inhibition of bicarbonate reabsorption with acetazolamide produces a slightly smaller reduction in sodium reabsorption (97-89%), an effect not seen in the absence of bicarbonate. Acetazolamide greatly increases phosphate excretion and free water clearance in a way consistent with suppression of proximal tubular reabsorption. By contrast, simple omission of bicarbonate from the perfusing medium does not alter phosphaturia or free water clearance. Reabsorption of bicarbonate appears to account for a fraction of sodium reabsorption roughly equivalent to the proportion of sodium associated stoichiometrically with bicarbonate in the glomerule filtrate. The data do not support the hypothesis that the development of a transtubular chloride gradient is critically important for the reabsorption of a large fraction of the glomerular filtrate."}
{"id": "PMID:236674", "title": "Effects of acid-base changes, hypoxia, and catecholamines on ventricular performance.", "content": "Extracellular pH changes were produced in dogs with tris (hydroxy-methyl)-aminomethane (Tris) or NaHCO3 in the presence or absence of hypoxemia and before and after beta-adrenergic blockade with propranolol. Ventricular performance (VP) was evaluated by measurement of maximum rate of rise of left ventricular pressure (dp/dt max) and left ventricular end-diastolic pressure in the canine right heart bypass preparation with aortic pressure, heart rate, and cardiac output held constant. Low pH diminished VP. Hypoxemia did not alter VP within the pH, suggesting that decreased V observed with acidosis before propranolol was due primarily to decreased myocardial response to catecholamines. Increase of pH with Tris increased VP significantly more than with NaHCO3. Beta blockade diminished the response of VP to Tris at a high pH;prior administration of reserpine abolished the inotropic effect of Tris. The data suggest that Tris can influence VP independent of its effect on pH. This effect is probably mediated by the interaction between endogenous catecholamines and myocardial beta receptors.", "contents": "Effects of acid-base changes, hypoxia, and catecholamines on ventricular performance. Extracellular pH changes were produced in dogs with tris (hydroxy-methyl)-aminomethane (Tris) or NaHCO3 in the presence or absence of hypoxemia and before and after beta-adrenergic blockade with propranolol. Ventricular performance (VP) was evaluated by measurement of maximum rate of rise of left ventricular pressure (dp/dt max) and left ventricular end-diastolic pressure in the canine right heart bypass preparation with aortic pressure, heart rate, and cardiac output held constant. Low pH diminished VP. Hypoxemia did not alter VP within the pH, suggesting that decreased V observed with acidosis before propranolol was due primarily to decreased myocardial response to catecholamines. Increase of pH with Tris increased VP significantly more than with NaHCO3. Beta blockade diminished the response of VP to Tris at a high pH;prior administration of reserpine abolished the inotropic effect of Tris. The data suggest that Tris can influence VP independent of its effect on pH. This effect is probably mediated by the interaction between endogenous catecholamines and myocardial beta receptors."}
{"id": "PMID:236675", "title": "Effect of temperature on rate of CO2 uptake by human red cell suspensions.", "content": "The time course of carbon dioxide uptake by oxygenated supensions of human red cells was followed using a CO2 electrode in a Hartridge-Roughton continuous-flow rapid-reaction apparatus. Measurements were made at several temperatures from 1i to 42 degrees C, with the initial PCO2 in the reacting mixture from 40 to 60 mmHg. The initial part of the uptake curve is presumably rate limited by the intracellular hydration of CO2 with reaction-velocity constants in cell water from 280 to 960 S-1 at 42 degrees C and an activation energy of 2.4 kcal mol-1. The later stages of CO2 uptake were much slower, with half-times from greater than 1.5 s at 12 degrees C to 0.7 s at 42 degrees C, and were presumably rate limited by the chloride-bicarbonate shift and H+ interchanges. The results indicate that despite the acceleration of the hydration reaction in cell water by a factor of 5,000 at 37 degrees C and 3,800 at 42 degrees C, the later part of the exchange is too slow to permit blood to come intoC02, equilibrium with actively exercising muscles during its passage through the capillary bed.", "contents": "Effect of temperature on rate of CO2 uptake by human red cell suspensions. The time course of carbon dioxide uptake by oxygenated supensions of human red cells was followed using a CO2 electrode in a Hartridge-Roughton continuous-flow rapid-reaction apparatus. Measurements were made at several temperatures from 1i to 42 degrees C, with the initial PCO2 in the reacting mixture from 40 to 60 mmHg. The initial part of the uptake curve is presumably rate limited by the intracellular hydration of CO2 with reaction-velocity constants in cell water from 280 to 960 S-1 at 42 degrees C and an activation energy of 2.4 kcal mol-1. The later stages of CO2 uptake were much slower, with half-times from greater than 1.5 s at 12 degrees C to 0.7 s at 42 degrees C, and were presumably rate limited by the chloride-bicarbonate shift and H+ interchanges. The results indicate that despite the acceleration of the hydration reaction in cell water by a factor of 5,000 at 37 degrees C and 3,800 at 42 degrees C, the later part of the exchange is too slow to permit blood to come intoC02, equilibrium with actively exercising muscles during its passage through the capillary bed."}
{"id": "PMID:236676", "title": "Effect of vagal innervation on the secretory responses of canine gastric pouches exposed to bile.", "content": "The changes in the secretory response to a meat meal, after preliminary exposure of vagally innervated and vagally denervated fundic pouches to ox bile at pH 7 and pH 2, have been defined. In the innervated pouches, exposure to bile at both pH levels caused transient inhibition of gastric acid secretion. In both types of pouch, the output of Na+ in the gastric juice was presistently increased due to enhanced exchange diffusion. The changes were more pronounced after exposure to bile at pH 2 than after exposure to bile at pH 7. After exposure to bile, exchange diffusion was more increased in the innervated pouches than in the denervated. The results suggested that the innervated mucosa was more susceptible than was the denervated mucosa to the injurious effects of bile.", "contents": "Effect of vagal innervation on the secretory responses of canine gastric pouches exposed to bile. The changes in the secretory response to a meat meal, after preliminary exposure of vagally innervated and vagally denervated fundic pouches to ox bile at pH 7 and pH 2, have been defined. In the innervated pouches, exposure to bile at both pH levels caused transient inhibition of gastric acid secretion. In both types of pouch, the output of Na+ in the gastric juice was presistently increased due to enhanced exchange diffusion. The changes were more pronounced after exposure to bile at pH 2 than after exposure to bile at pH 7. After exposure to bile, exchange diffusion was more increased in the innervated pouches than in the denervated. The results suggested that the innervated mucosa was more susceptible than was the denervated mucosa to the injurious effects of bile."}
{"id": "PMID:236677", "title": "Screening tonometry by technicians.", "content": "Comparative measurements of intraocular pressure of 200 eyes were statistical analyzed. Goldmann applanation tonometry was performed by the author and was accepted as a reference system for the measurements made by a technician using the Pneumatonograph, the GlaucoTest screening tonometer, the Halberg tonometer and the Schiotz tonometer. The technician was trained in the use of these instruments for two days; The Pneumatonograph results on seated patients were in good agreement with the Goldmann readings. The GlaucoTest screening tonometer proved to be a good screening instrument for ocular hypertensives and required only a short period of training for the technician. The Halberg tonometer did not give precise readings of intraocular pressure, however, it was more difficult for technicians to use. The Sciotz tonometer appeared to be of limited value in screening tonometry. Some aspects of the influence of body position on i.o; pressure in the different tonometric procedures have been discussed.", "contents": "Screening tonometry by technicians. Comparative measurements of intraocular pressure of 200 eyes were statistical analyzed. Goldmann applanation tonometry was performed by the author and was accepted as a reference system for the measurements made by a technician using the Pneumatonograph, the GlaucoTest screening tonometer, the Halberg tonometer and the Schiotz tonometer. The technician was trained in the use of these instruments for two days; The Pneumatonograph results on seated patients were in good agreement with the Goldmann readings. The GlaucoTest screening tonometer proved to be a good screening instrument for ocular hypertensives and required only a short period of training for the technician. The Halberg tonometer did not give precise readings of intraocular pressure, however, it was more difficult for technicians to use. The Sciotz tonometer appeared to be of limited value in screening tonometry. Some aspects of the influence of body position on i.o; pressure in the different tonometric procedures have been discussed."}
{"id": "PMID:236679", "title": "The effects of a dry heat blood warmer on some components of stored blood.", "content": "The plasma potassium, sodium, pH and haemoglobin of stored acid dextrose blood were measured after various periods of storage and after passage through a Fenwall R 4301 dry heat blood warmer. No significant changes were observed except a slight rise in plasma haemoglobin concentration.", "contents": "The effects of a dry heat blood warmer on some components of stored blood. The plasma potassium, sodium, pH and haemoglobin of stored acid dextrose blood were measured after various periods of storage and after passage through a Fenwall R 4301 dry heat blood warmer. No significant changes were observed except a slight rise in plasma haemoglobin concentration."}
{"id": "PMID:236702", "title": "The mechanism of the positive chronotropic action of diethyl ether on rat atria.", "content": "Diethyl ether elicited a dose-dependent increase in the intrinsic frequency of contraction of isolated rat atrial preparations. The maximum effect (plus 34 per cent) occurred with 230 mg ether/100 ml medium. This ether concentration corresponds to a partial pressure of 29.2 mm Hg or 3 MAC. The positive chronotropic action of ether was not reduced in atria obtained from rats pretreated with reserpine (4 mg/kg, ip) although this treatment markedly reduced the effect of tyramine on frequency of contraction. The positive chronotropic response to 0.01 muM isoproterenol was inhibited by the beta-adrenergic antagonist 0.3 mgM dl-propranolol but remained unimpaired in the presence of 0.3 mgM d-propranolol (a much weaker antagonist). In contrast, the atrial response to ether was similar in the presence of either d- or dl-propranolol. Atropine, in concentrations that completely blocked the negative chronotropic action of acetylcholine, did not increase the frequency of contraction, suggesting that the positive chronotropic effect of ether is not due to an atropine-like activity of ether. Our results indicate that the positive chronotropic effect of ether on isolated rat atrial preparations is not mediated via catecholamine release, nor does it represent direct stimulation of beta-adrenergic receptors or block of cholinergic receptors. (Key words: Anesthetics, volatile, diethyl ether; Heart, atria, diethyl ether.).", "contents": "The mechanism of the positive chronotropic action of diethyl ether on rat atria. Diethyl ether elicited a dose-dependent increase in the intrinsic frequency of contraction of isolated rat atrial preparations. The maximum effect (plus 34 per cent) occurred with 230 mg ether/100 ml medium. This ether concentration corresponds to a partial pressure of 29.2 mm Hg or 3 MAC. The positive chronotropic action of ether was not reduced in atria obtained from rats pretreated with reserpine (4 mg/kg, ip) although this treatment markedly reduced the effect of tyramine on frequency of contraction. The positive chronotropic response to 0.01 muM isoproterenol was inhibited by the beta-adrenergic antagonist 0.3 mgM dl-propranolol but remained unimpaired in the presence of 0.3 mgM d-propranolol (a much weaker antagonist). In contrast, the atrial response to ether was similar in the presence of either d- or dl-propranolol. Atropine, in concentrations that completely blocked the negative chronotropic action of acetylcholine, did not increase the frequency of contraction, suggesting that the positive chronotropic effect of ether is not due to an atropine-like activity of ether. Our results indicate that the positive chronotropic effect of ether on isolated rat atrial preparations is not mediated via catecholamine release, nor does it represent direct stimulation of beta-adrenergic receptors or block of cholinergic receptors. (Key words: Anesthetics, volatile, diethyl ether; Heart, atria, diethyl ether.)."}
{"id": "PMID:236703", "title": "Lidocaine and its metabolites in the newborn.", "content": "Concentrations of lidocaine and its metabolites were measured chromatographically in the blood and urine of mothers and babies after epidural administration of lidocaine to the mother for cesarean delivery. Delivery occurred a mean time of 29.83 plus or minus 8.64 minutes after a mean dose of 398.33 plus or minus 63.38 mg to the mother, at which time mean maternal venous plasma concentration was 1.70 plus or minus 0.77 mug/ml. Of the total molar quantity of lidocaine and metabolite recovered from the newborns' urine in the first 12 hours of life, 50.63 per cent appeared as unchanged lidocaine, while 49.37 per cent appeared as metabolites. In the second 12 hours of life, 23.37 per cent appeared as unchanged lidocaine, while 76.63 per cent appeared as metabolites. We conclude that the greater proportion of metabolite excretion in the second 12 hours is evidence that the new born is capable of metabolizing lidocaine.", "contents": "Lidocaine and its metabolites in the newborn. Concentrations of lidocaine and its metabolites were measured chromatographically in the blood and urine of mothers and babies after epidural administration of lidocaine to the mother for cesarean delivery. Delivery occurred a mean time of 29.83 plus or minus 8.64 minutes after a mean dose of 398.33 plus or minus 63.38 mg to the mother, at which time mean maternal venous plasma concentration was 1.70 plus or minus 0.77 mug/ml. Of the total molar quantity of lidocaine and metabolite recovered from the newborns' urine in the first 12 hours of life, 50.63 per cent appeared as unchanged lidocaine, while 49.37 per cent appeared as metabolites. In the second 12 hours of life, 23.37 per cent appeared as unchanged lidocaine, while 76.63 per cent appeared as metabolites. We conclude that the greater proportion of metabolite excretion in the second 12 hours is evidence that the new born is capable of metabolizing lidocaine."}
{"id": "PMID:236701", "title": "Acid-base disorders: application of total body carbon dioxide titration in anesthesia.", "content": "Every anesthesiologist is aware of the importance of acid-base determinations, but the multiplicity of duties required in clinical anesthesia often leave time for blood-gas measurements at most. The author presents a relatively simple four-step system for more complete interpretation, with biomathematical back-grounding. In summary, he points out that the dominant parameter remains the patient's clinical history in relation to hydrogen ion, Paco2, and bicarbonate.", "contents": "Acid-base disorders: application of total body carbon dioxide titration in anesthesia. Every anesthesiologist is aware of the importance of acid-base determinations, but the multiplicity of duties required in clinical anesthesia often leave time for blood-gas measurements at most. The author presents a relatively simple four-step system for more complete interpretation, with biomathematical back-grounding. In summary, he points out that the dominant parameter remains the patient's clinical history in relation to hydrogen ion, Paco2, and bicarbonate."}
{"id": "PMID:236705", "title": "Sodium bicarbonate and systemic hemodynamics in volunteers anesthetized with halothane.", "content": "The cardiovascular effects of acute metabolic alkalosis (NaHCO3) in normal male volunteers anesthetized with halothane were measured. Pure metabolic alkalosis was studied by maintaning the end-tidal carbon dioxide tension at 40 torr. In each subject, cardiac index increased and total peripheral resistance decreased after each dose of NaHCO3. The increased cardiac index was associated with increased central blood volume, left ventricular minute work index, stroke index, and heart rate. Systolic time intervals showed increased myocardial performance. NaHCO3 administered to volunteers whose hearts were depressed by halothane appeared to cause peripheral vasodilation, volume expansion, and myocardial stimulation. The authors conclude that NaHCO3 administered during halothane anesthesia decreases total peripheral resistance and may lead to severe hypotension.", "contents": "Sodium bicarbonate and systemic hemodynamics in volunteers anesthetized with halothane. The cardiovascular effects of acute metabolic alkalosis (NaHCO3) in normal male volunteers anesthetized with halothane were measured. Pure metabolic alkalosis was studied by maintaning the end-tidal carbon dioxide tension at 40 torr. In each subject, cardiac index increased and total peripheral resistance decreased after each dose of NaHCO3. The increased cardiac index was associated with increased central blood volume, left ventricular minute work index, stroke index, and heart rate. Systolic time intervals showed increased myocardial performance. NaHCO3 administered to volunteers whose hearts were depressed by halothane appeared to cause peripheral vasodilation, volume expansion, and myocardial stimulation. The authors conclude that NaHCO3 administered during halothane anesthesia decreases total peripheral resistance and may lead to severe hypotension."}
{"id": "PMID:236706", "title": "Fluroxene and isolated heart muscle.", "content": "The direct myocardial effects of fluroxene were examined in isometrically and isotonically contracting isolated rat heart muscle. MAC, the minimum anesthetic concentration needed to prevent movement in response to tail clamping, was found to be 5.0 vol per cent fluroxene in the rat. At 4.6 vol per cent fluroxene, peak developed isometric tension and maximum rate of tension development were decreased 29 and 24 per cent, respectively. At 11 vol per cent, the depressions were 39 and 33 per cent. At 26.4 vol per cent, the depressions were around 60 per cent. Vmax (the maximum shortening velocity of unloaded muscle) of the force-velocity relation was unaltered by fluroxene concentrations of 0.8, 4.6, and 11 vol per cent. Even at 26.4 vol per cent, the depression in Vmax was only 25 per cent. Po (the maximum force at zero velocity), work, and power were lowered much more, with reductions ranging from 15 to 27 per cent at 4.6 vol per cent, from 40 to 42 per cent at 11.0 vol per cent, and from 65 to 69 per cent at the 26.4 vol per cent. Series elastic extension was unchanged at 0.8 and 4.6 vol per cent fluroxene, but was decreased 16 per cent at 11.0 vol per cent and 46 per cent at 26.4 vol per cent fluroxene. The data indicate the fluroxene has a direct negative inotropic effect that is associated with increased series elastic stiffness, but does not involve Vmax of the force-velocity relation until quite high anesthestic concentrations are reached. Comparative studies were also carried out with halothane. MAC for halothane in the rat was 1.0 vol per cent. The relative potency of halothane compared with fluroxene in depression of Vmax was 13.2, and its relative potency in depression of Po, 4.0.", "contents": "Fluroxene and isolated heart muscle. The direct myocardial effects of fluroxene were examined in isometrically and isotonically contracting isolated rat heart muscle. MAC, the minimum anesthetic concentration needed to prevent movement in response to tail clamping, was found to be 5.0 vol per cent fluroxene in the rat. At 4.6 vol per cent fluroxene, peak developed isometric tension and maximum rate of tension development were decreased 29 and 24 per cent, respectively. At 11 vol per cent, the depressions were 39 and 33 per cent. At 26.4 vol per cent, the depressions were around 60 per cent. Vmax (the maximum shortening velocity of unloaded muscle) of the force-velocity relation was unaltered by fluroxene concentrations of 0.8, 4.6, and 11 vol per cent. Even at 26.4 vol per cent, the depression in Vmax was only 25 per cent. Po (the maximum force at zero velocity), work, and power were lowered much more, with reductions ranging from 15 to 27 per cent at 4.6 vol per cent, from 40 to 42 per cent at 11.0 vol per cent, and from 65 to 69 per cent at the 26.4 vol per cent. Series elastic extension was unchanged at 0.8 and 4.6 vol per cent fluroxene, but was decreased 16 per cent at 11.0 vol per cent and 46 per cent at 26.4 vol per cent fluroxene. The data indicate the fluroxene has a direct negative inotropic effect that is associated with increased series elastic stiffness, but does not involve Vmax of the force-velocity relation until quite high anesthestic concentrations are reached. Comparative studies were also carried out with halothane. MAC for halothane in the rat was 1.0 vol per cent. The relative potency of halothane compared with fluroxene in depression of Vmax was 13.2, and its relative potency in depression of Po, 4.0."}
{"id": "PMID:236707", "title": "Humoral immunity to a metabolite of halothane, fluroxene, and enflurane.", "content": "Trifluoroacetate, a common metabolite of halothane, fluroxene, and enflurane, conjugated to guinea-pig albumin elicits specific serum antibody in guinea pigs. Two classes of antibodies were found: hemolytic, gamma-2, and anaphylactic, gamma-1. Repeated injections of the antigen, trifluoroacetyl-guinea pig albumin, often led to disappearance of circulating antibodies.", "contents": "Humoral immunity to a metabolite of halothane, fluroxene, and enflurane. Trifluoroacetate, a common metabolite of halothane, fluroxene, and enflurane, conjugated to guinea-pig albumin elicits specific serum antibody in guinea pigs. Two classes of antibodies were found: hemolytic, gamma-2, and anaphylactic, gamma-1. Repeated injections of the antigen, trifluoroacetyl-guinea pig albumin, often led to disappearance of circulating antibodies."}
{"id": "PMID:236710", "title": "Pneumococcal isolations from patients with pneumonia and control subjects in a prepaid medical care group.", "content": "The incidence of pneumococcal infections and pneumonia among the 150,000 members of a prepaid medical care group in Seattle was assessed by an intensive study of outpatients for one year from June 1971 through May 1972. Respiratory specimens (sputum, pharyngeal, and nasal) from patients with pneumonia or febrile respiratory disease and from age- and sex-matched control subjects were cultured for pneumococci on media and in mice. Total rate of pneumonia was 11 per 1,000. Twenty-four per cent of patients with pneumonia and 12 per cent of control subjects carried pneumococci. The patients with pneumonia from whom the pneumococcus was isolated did not differ clinically on average from those without such isolates. Lobar and bacteremic pneumonia were extremely rare. The rate of pneumococcal infections and carriers was highest in the spring. Although young children had the highest rate of pneumonia from all causes there was no difference in the isolation rate between ill children and control children. The highest rate attributable to pneumococci was in those larger than 40 years of age. Pneumococcal carrier rates were much lower than those reported in the 1930s. Thirty-nine per cent of patients with pneumonia had evidence of viral or mycoplasmal infection, as determined primarily by serologic methods. Pneumococcal pneumonia was not a serious problem in this average, employed population in Seattle.", "contents": "Pneumococcal isolations from patients with pneumonia and control subjects in a prepaid medical care group. The incidence of pneumococcal infections and pneumonia among the 150,000 members of a prepaid medical care group in Seattle was assessed by an intensive study of outpatients for one year from June 1971 through May 1972. Respiratory specimens (sputum, pharyngeal, and nasal) from patients with pneumonia or febrile respiratory disease and from age- and sex-matched control subjects were cultured for pneumococci on media and in mice. Total rate of pneumonia was 11 per 1,000. Twenty-four per cent of patients with pneumonia and 12 per cent of control subjects carried pneumococci. The patients with pneumonia from whom the pneumococcus was isolated did not differ clinically on average from those without such isolates. Lobar and bacteremic pneumonia were extremely rare. The rate of pneumococcal infections and carriers was highest in the spring. Although young children had the highest rate of pneumonia from all causes there was no difference in the isolation rate between ill children and control children. The highest rate attributable to pneumococci was in those larger than 40 years of age. Pneumococcal carrier rates were much lower than those reported in the 1930s. Thirty-nine per cent of patients with pneumonia had evidence of viral or mycoplasmal infection, as determined primarily by serologic methods. Pneumococcal pneumonia was not a serious problem in this average, employed population in Seattle."}
{"id": "PMID:236713", "title": "Effects of dimethyl sulfoxide on subunit proteins.", "content": "The effects of DMSO are thought to result from the formation of hydrogen bonds with proton-donor groups on biopolymers, which are stronger than those formed with water. Since DMSO contains methyl groups, however, effects on hydrophobic bonding in proteins could be expected at higher DMSO levels. Our studies of the effects of DMSO on model subunit proteins can be interpreted in the above terms. At a concentration of 20% or less, DMSO changed glutamate dehydrogenase into the inactive monomer and the effects were fully reversible with the activator (ADP). Higher DMSO levels resulted in irreversible inactivation. The predominant effect noted on beta-glucuronidase was irreversible inactivation by 20% or more DMSO at 37 degrees C. Purified beta-glucuronidase exhibited an activation in 20% DMSO at high substrate levels; this resulted from an apparent substrate inhibition in the absence of DMSO. DMSO inhibited the clotting of fibrinogen by purified thrombin, but the major effect appeared to be due to competition between thrombin and DMSO for binding sites on fibrinogen. These effects appear to be largely due to interactions between DMSO and hydrophobic bonding in fibrinogen, although DMSO also appears to interfere with the aggregation of fibrin monomers through its effects on hydrophilic groups. These results suggest that reversible alterations in protein structure are the major effect of exposure of subunit proteins to low DMSO levels at low temperatues, while irreversible denaturation of subunit proteins may be an appreciable effect a higher temperatures and higher DMSO concentrations.", "contents": "Effects of dimethyl sulfoxide on subunit proteins. The effects of DMSO are thought to result from the formation of hydrogen bonds with proton-donor groups on biopolymers, which are stronger than those formed with water. Since DMSO contains methyl groups, however, effects on hydrophobic bonding in proteins could be expected at higher DMSO levels. Our studies of the effects of DMSO on model subunit proteins can be interpreted in the above terms. At a concentration of 20% or less, DMSO changed glutamate dehydrogenase into the inactive monomer and the effects were fully reversible with the activator (ADP). Higher DMSO levels resulted in irreversible inactivation. The predominant effect noted on beta-glucuronidase was irreversible inactivation by 20% or more DMSO at 37 degrees C. Purified beta-glucuronidase exhibited an activation in 20% DMSO at high substrate levels; this resulted from an apparent substrate inhibition in the absence of DMSO. DMSO inhibited the clotting of fibrinogen by purified thrombin, but the major effect appeared to be due to competition between thrombin and DMSO for binding sites on fibrinogen. These effects appear to be largely due to interactions between DMSO and hydrophobic bonding in fibrinogen, although DMSO also appears to interfere with the aggregation of fibrin monomers through its effects on hydrophilic groups. These results suggest that reversible alterations in protein structure are the major effect of exposure of subunit proteins to low DMSO levels at low temperatues, while irreversible denaturation of subunit proteins may be an appreciable effect a higher temperatures and higher DMSO concentrations."}
{"id": "PMID:236721", "title": "Induction of T-cells differentiation in vitro by thymus epithelial cells.", "content": "Thymus-reticular epithelial cells (TE-cells) were grown in a cell culture devoid of any lymphocytic elements. These cells were able to induce T-cell differentiation in spleen cells from T-dificient mice as expressed by con-A responsiveness and GvH reactivity. It was also shown that xenogeneic rat TE cells were as effective in the induction of T-cell differentiation in vitro as syngeneic TE cells. This system is therefore ideal for the study of T-cell development.", "contents": "Induction of T-cells differentiation in vitro by thymus epithelial cells. Thymus-reticular epithelial cells (TE-cells) were grown in a cell culture devoid of any lymphocytic elements. These cells were able to induce T-cell differentiation in spleen cells from T-dificient mice as expressed by con-A responsiveness and GvH reactivity. It was also shown that xenogeneic rat TE cells were as effective in the induction of T-cell differentiation in vitro as syngeneic TE cells. This system is therefore ideal for the study of T-cell development."}
{"id": "PMID:236734", "title": "Methylmalonic acidaemia and nonketotic hyperglycinaemia. Clinical and biochemical aspects.", "content": "The clinical and metabolic data of 2 cases of methylmalonic acidaemia with propionic acidaemia are reported together with those of 3 other patients with nonketotic hyperglycinaemia. Liver enzymatic studies showed decreased activity in vitro of the glycine cleavage enzyme in one patient with methylmalonic acidaemia as well as in 2 unrelated patients with nonketotic hyperglycinaemia, while the activity of the serine hydroxymethylase enzyme was normal. Hyperammonaemia was substantiated in one patient with methylmalonic acidaemia and also in one child with nonketotic hyperglycinaemia. The activity of the enzymes of the urea cycle, determined in the liver of this nonketotic child, was normal except for a decrease of the carbamyl phosphate synthetase enzyme to 15% of normal.", "contents": "Methylmalonic acidaemia and nonketotic hyperglycinaemia. Clinical and biochemical aspects. The clinical and metabolic data of 2 cases of methylmalonic acidaemia with propionic acidaemia are reported together with those of 3 other patients with nonketotic hyperglycinaemia. Liver enzymatic studies showed decreased activity in vitro of the glycine cleavage enzyme in one patient with methylmalonic acidaemia as well as in 2 unrelated patients with nonketotic hyperglycinaemia, while the activity of the serine hydroxymethylase enzyme was normal. Hyperammonaemia was substantiated in one patient with methylmalonic acidaemia and also in one child with nonketotic hyperglycinaemia. The activity of the enzymes of the urea cycle, determined in the liver of this nonketotic child, was normal except for a decrease of the carbamyl phosphate synthetase enzyme to 15% of normal."}
{"id": "PMID:236735", "title": "Leaching and degradation of 4-aminopyridine-14C in several soil systems.", "content": "Leaching and degradation of 4-aminopyridine (a frightening agent for protecting grain crops from blackbirds) was studied in seven soils. Carbon 14-labeled 4-aminopyridine was strongly adsorbed onto soil colloids, with the degree of adsorption related to pH. Application of seven in. of simulated rainfall over 20 days to surface-treated alkaline soils leached to 0.02 percent to 0.18 percent of the -14C; radioactivity was detected in the runoff from only one of the four acidic soils. Degradation of 4-aminopyridine-14C to -14CO(2) was negligible in soils incubated up to two months under anaerobic conditions. Under aerobic incubation, there was a one-week lag before extensive breakdown began. Degradation rates increased with increasing temperature and soil moisture during incubation, but soil composition had a greater influence. After three months at 30 degrees C and 50 percent moisture, evolution of -14CO(2) ranged from 0.4 percent for a highly acidic loam (pH 4.1) to more than 50 percent for a lighter-textured, alkaline, loamy sand (pH 7.8); the half-life of 4-aminopyridine in soils under these test conditions ranged from 3 to more than 22 months. A theoretical scheme is presented for the degradation of 4-aminopyridine in soils.", "contents": "Leaching and degradation of 4-aminopyridine-14C in several soil systems. Leaching and degradation of 4-aminopyridine (a frightening agent for protecting grain crops from blackbirds) was studied in seven soils. Carbon 14-labeled 4-aminopyridine was strongly adsorbed onto soil colloids, with the degree of adsorption related to pH. Application of seven in. of simulated rainfall over 20 days to surface-treated alkaline soils leached to 0.02 percent to 0.18 percent of the -14C; radioactivity was detected in the runoff from only one of the four acidic soils. Degradation of 4-aminopyridine-14C to -14CO(2) was negligible in soils incubated up to two months under anaerobic conditions. Under aerobic incubation, there was a one-week lag before extensive breakdown began. Degradation rates increased with increasing temperature and soil moisture during incubation, but soil composition had a greater influence. After three months at 30 degrees C and 50 percent moisture, evolution of -14CO(2) ranged from 0.4 percent for a highly acidic loam (pH 4.1) to more than 50 percent for a lighter-textured, alkaline, loamy sand (pH 7.8); the half-life of 4-aminopyridine in soils under these test conditions ranged from 3 to more than 22 months. A theoretical scheme is presented for the degradation of 4-aminopyridine in soils."}
{"id": "PMID:236736", "title": "Delta-pH method for measuring blood cholinesterase. A study on the effect of temperature.", "content": "Efforts to evaluate precision of the Michel delta pH method for blood cholinesterase, performed in a beaker immersed in a 25 C water bath, resulted in unexpected variability in results of daily and day-to-day replicate analyses. Most disturbing was the considerable variation between each four-hour period of an eight-hour day (AM and PM measurements). Precision of quadruplicate sets, expressed as coefficient of variation, ranged from  plus or minus 0.5% to 8.5%. By rigidly controlling temperature with a water-jacketed reaction vessel the variation was reduced to plus or minus 1.7%. A study of effect of temperature on the method showed that a one-degree change in temperature resulted in a 5.5% change in plasma activity and a 3.0% change in red blood cell (RBC) activity. A graphing of the influence of temperature on reaction rate produced a linear relationship. Identical thermodynamic data were obtained with plasma and RBC samples that were inhibited 50% with an irreversible anticholinesterase agent.", "contents": "Delta-pH method for measuring blood cholinesterase. A study on the effect of temperature. Efforts to evaluate precision of the Michel delta pH method for blood cholinesterase, performed in a beaker immersed in a 25 C water bath, resulted in unexpected variability in results of daily and day-to-day replicate analyses. Most disturbing was the considerable variation between each four-hour period of an eight-hour day (AM and PM measurements). Precision of quadruplicate sets, expressed as coefficient of variation, ranged from  plus or minus 0.5% to 8.5%. By rigidly controlling temperature with a water-jacketed reaction vessel the variation was reduced to plus or minus 1.7%. A study of effect of temperature on the method showed that a one-degree change in temperature resulted in a 5.5% change in plasma activity and a 3.0% change in red blood cell (RBC) activity. A graphing of the influence of temperature on reaction rate produced a linear relationship. Identical thermodynamic data were obtained with plasma and RBC samples that were inhibited 50% with an irreversible anticholinesterase agent."}
{"id": "PMID:236737", "title": "Evaluation of the Nissen fundoplication for treatment of hiatal hernia: use of parietal cell vagotomy without drainage as an adjunctive procedure.", "content": "Twenty-nine patients who underwent Nissen fundoplication for the treatment of symptomatic, sliding, esophageal hiatal hernia are reported. Fourteen of these patients also underwent parietal cell vagotomy (PCV) without a drainage procedure. Simulatenous cineradiography and manometric studies, esophagoscopy and gastric analysis were performed pre- and postoperatively. Esophageal acid clearing and pH reflux studies were performed postoperatively. All but 3 patients had reflux and/or esophagitis preoperatively. Cineradiography and the pH reflux test were the most reliable tests for diagnosis of reflux. There was no operative mortality. The mean followup period was 20 months. Dysphagia occurred in 5 patients. Correction of dysphagia in one patient required operation. The dysphagia in the remaining patients was temporary and mild, responding to dilatation. Two patients had mild diarrhea. One patient who had had a previous gastric resection developed severe diarrhea after bilateral truncal vagotomy. No patient developed the \"bloat syndrome\". A close correlation did not exist between reflux and preoperative sphincter pressure. The mean LES pressure increased 10 mmH2O postoperatively and the two patients with persistent reflux postoperatively had normal LES pressure. Correction of reflux after Nissen fundoplication is probably due to some mechanism other than increased LES pressure. Recurrent or persistent hiatal hernia was diagnosed in 4 patients by cineradiography. Two of these patients had reflux but only the patient who had undergone PCV was without symptoms or esophagitis. The technical performance of the Nissen hiatal hernia repair was greatly facilitat  ed by PCV. This procedure also provided adequate treatment for patients with concomitant duodenal ulcer disease. PCV, unaccompanied by a drainage procedure, was not associated with increased morbidity, mortality or the adverse effects usually attributed to vagotomy. In the event of recurrent hernia and reflux, PCV may prevent the development of esophagitis.", "contents": "Evaluation of the Nissen fundoplication for treatment of hiatal hernia: use of parietal cell vagotomy without drainage as an adjunctive procedure. Twenty-nine patients who underwent Nissen fundoplication for the treatment of symptomatic, sliding, esophageal hiatal hernia are reported. Fourteen of these patients also underwent parietal cell vagotomy (PCV) without a drainage procedure. Simulatenous cineradiography and manometric studies, esophagoscopy and gastric analysis were performed pre- and postoperatively. Esophageal acid clearing and pH reflux studies were performed postoperatively. All but 3 patients had reflux and/or esophagitis preoperatively. Cineradiography and the pH reflux test were the most reliable tests for diagnosis of reflux. There was no operative mortality. The mean followup period was 20 months. Dysphagia occurred in 5 patients. Correction of dysphagia in one patient required operation. The dysphagia in the remaining patients was temporary and mild, responding to dilatation. Two patients had mild diarrhea. One patient who had had a previous gastric resection developed severe diarrhea after bilateral truncal vagotomy. No patient developed the \"bloat syndrome\". A close correlation did not exist between reflux and preoperative sphincter pressure. The mean LES pressure increased 10 mmH2O postoperatively and the two patients with persistent reflux postoperatively had normal LES pressure. Correction of reflux after Nissen fundoplication is probably due to some mechanism other than increased LES pressure. Recurrent or persistent hiatal hernia was diagnosed in 4 patients by cineradiography. Two of these patients had reflux but only the patient who had undergone PCV was without symptoms or esophagitis. The technical performance of the Nissen hiatal hernia repair was greatly facilitat  ed by PCV. This procedure also provided adequate treatment for patients with concomitant duodenal ulcer disease. PCV, unaccompanied by a drainage procedure, was not associated with increased morbidity, mortality or the adverse effects usually attributed to vagotomy. In the event of recurrent hernia and reflux, PCV may prevent the development of esophagitis."}
{"id": "PMID:236738", "title": "Septic lung and shock lung in man.", "content": "Two series of patients were studied by serial measurements of blood gas exchange and pulmonarmonary dysfunction and to evaluate the dangers of respiratory failure in post traumatic patients. There were 27 patients who had sustained profound hemorrhagic shock and massive blood replacement averaging 9.7 liters and 38 patients who suffered general peritonitis or other forms of fulminating nonthoracic sepsis. All were supported by endotrachael intubation and volume controlled ventilators. The overall mortality for the post shock patients without sepsis was 12% while in the septic patients it was 35%. The maximal pulmonary arteriovenous shunt encountered in the post hemorrhagic shock patients at 36 hours averaged 20 plus or minus 8% and was accompanied by high cardiac indices (average 5.1 plus or minus 1.3 L/M-2/min) but no significant rise of pulmonary arterial pressure or peak inspiratory pressure (PIP). Severe pulmonary dysfunction subsequently occurred only in those patients who later became septic. The studies on the septic patients were divided according to the magnitude of the cardiac indices (the high indices averaged 4.8 plus or minus 1.6L/M-2/min) and thelow indices averaged 1.9 plus or minus 1.0 L/M-2/min. In the former, the average maximal shunt of 30 plus or minus 6% was sustained for 4 or more days, accompanied by an elevation of PIP to 36 plus or minus 6 cm H2O and by Pa pressure of 28 plus or minus 5 mm Hg. The patients in low output septic shock usually had an associated bronchopneumonia and had an average venous admixture of 34 plus or minus 8% and PIP values of 41 plus or minus 8 cm H2O. The mean Pa pressure in this group was 29 plus or minus 6 mm Hg.", "contents": "Septic lung and shock lung in man. Two series of patients were studied by serial measurements of blood gas exchange and pulmonarmonary dysfunction and to evaluate the dangers of respiratory failure in post traumatic patients. There were 27 patients who had sustained profound hemorrhagic shock and massive blood replacement averaging 9.7 liters and 38 patients who suffered general peritonitis or other forms of fulminating nonthoracic sepsis. All were supported by endotrachael intubation and volume controlled ventilators. The overall mortality for the post shock patients without sepsis was 12% while in the septic patients it was 35%. The maximal pulmonary arteriovenous shunt encountered in the post hemorrhagic shock patients at 36 hours averaged 20 plus or minus 8% and was accompanied by high cardiac indices (average 5.1 plus or minus 1.3 L/M-2/min) but no significant rise of pulmonary arterial pressure or peak inspiratory pressure (PIP). Severe pulmonary dysfunction subsequently occurred only in those patients who later became septic. The studies on the septic patients were divided according to the magnitude of the cardiac indices (the high indices averaged 4.8 plus or minus 1.6L/M-2/min) and thelow indices averaged 1.9 plus or minus 1.0 L/M-2/min. In the former, the average maximal shunt of 30 plus or minus 6% was sustained for 4 or more days, accompanied by an elevation of PIP to 36 plus or minus 6 cm H2O and by Pa pressure of 28 plus or minus 5 mm Hg. The patients in low output septic shock usually had an associated bronchopneumonia and had an average venous admixture of 34 plus or minus 8% and PIP values of 41 plus or minus 8 cm H2O. The mean Pa pressure in this group was 29 plus or minus 6 mm Hg."}
{"id": "PMID:236739", "title": "Evaluation of biliary and pancreatic function in pancreolithiasis. Value of the determination of gamma-glutamyl transpeptidase.", "content": "Ten patients with pancreolithiasis and ten controls underwent a 110-minute pancreozymin-secretion test in which post-pancreozymin collection periods were prolonged to 30 minutes. Gamma-Glutamyl transpeptidase concentrations and outputs of duodenal aspirate in response to pancreozymin and to secretin were greatly increased in patients with pancreolithiasis. No correlation was noted between gamma-glutamyl transpeptidase and bile pigment concentrations. The mean concentrations and outputs of amylase in disease were much less than those in control subjects throughout the test. Two categories of pancreolithiasis were distinguished with respect to the distribution and size of the calculi and amylase secretion. We suggest that, in pancreolithiasis, there is an increase in ductal or centroacinar cell mass.", "contents": "Evaluation of biliary and pancreatic function in pancreolithiasis. Value of the determination of gamma-glutamyl transpeptidase. Ten patients with pancreolithiasis and ten controls underwent a 110-minute pancreozymin-secretion test in which post-pancreozymin collection periods were prolonged to 30 minutes. Gamma-Glutamyl transpeptidase concentrations and outputs of duodenal aspirate in response to pancreozymin and to secretin were greatly increased in patients with pancreolithiasis. No correlation was noted between gamma-glutamyl transpeptidase and bile pigment concentrations. The mean concentrations and outputs of amylase in disease were much less than those in control subjects throughout the test. Two categories of pancreolithiasis were distinguished with respect to the distribution and size of the calculi and amylase secretion. We suggest that, in pancreolithiasis, there is an increase in ductal or centroacinar cell mass."}
{"id": "PMID:236741", "title": "Acetazolamide treatment of hypokalemic periodic paralysis. Probable mechanism of action.", "content": "Following administration of glucose and insulin to three patients with hypokalemic periodic paralysis, serum K+ fell 1.9 mM. After administration of acetazolamide, 250 mg four times daily, serum K+ fell 0.9 mM, a substantial difference. In normal persons glucose and insulin lowered serum K+ 0.5 mM, and this was not changed substantially by acetazolamide. The metabolic acidosis induced by the drug appears to be responsible for the change in decrement of serum K+ and for the amelioration of symptoms in the patients. The findings agree with earlier reports that metabolic acidosis lowers the rate of entry of K+ into muscle, thus opposing the heightened or pathological entry of K+ into muscle cells during attacks of the disease.", "contents": "Acetazolamide treatment of hypokalemic periodic paralysis. Probable mechanism of action. Following administration of glucose and insulin to three patients with hypokalemic periodic paralysis, serum K+ fell 1.9 mM. After administration of acetazolamide, 250 mg four times daily, serum K+ fell 0.9 mM, a substantial difference. In normal persons glucose and insulin lowered serum K+ 0.5 mM, and this was not changed substantially by acetazolamide. The metabolic acidosis induced by the drug appears to be responsible for the change in decrement of serum K+ and for the amelioration of symptoms in the patients. The findings agree with earlier reports that metabolic acidosis lowers the rate of entry of K+ into muscle, thus opposing the heightened or pathological entry of K+ into muscle cells during attacks of the disease."}
{"id": "PMID:236742", "title": "[Experimental changes of the pH in the middle ear and its effect on the internal ear (author's transl)].", "content": "Irrespective of their highly differing pH-value many pharmaca are nowadays applied to the middle ear. Animal experiments are to answer the question, weather changes in the pH-value of the middle ear may cause internal ear damages, With local application of different buffers (2.3-9.1 pH) into the tympanic cavity, the membrane of the round window was examined by means of the surface preparation technique, the pH-value of the perilymph was measured and the hair cells of the organ of corti were counted and histologically evaluated. With the reduction of the pH-value in the middle ear from 4.0 to 2.3 an increasing damage of the round window membrane could be detected. The pH-value of the perilymph, however, showed only a slight statistical variation, which cannot be guaranteed. After multiple applications of extremely acid buffers into the tympanic cavity directly before the round window membrane, a small but statistically significant reduction in the pH-value of the perilymph could be noticed. Hair cell damages at the organ of corti could in no case be observed.", "contents": "[Experimental changes of the pH in the middle ear and its effect on the internal ear (author's transl)]. Irrespective of their highly differing pH-value many pharmaca are nowadays applied to the middle ear. Animal experiments are to answer the question, weather changes in the pH-value of the middle ear may cause internal ear damages, With local application of different buffers (2.3-9.1 pH) into the tympanic cavity, the membrane of the round window was examined by means of the surface preparation technique, the pH-value of the perilymph was measured and the hair cells of the organ of corti were counted and histologically evaluated. With the reduction of the pH-value in the middle ear from 4.0 to 2.3 an increasing damage of the round window membrane could be detected. The pH-value of the perilymph, however, showed only a slight statistical variation, which cannot be guaranteed. After multiple applications of extremely acid buffers into the tympanic cavity directly before the round window membrane, a small but statistically significant reduction in the pH-value of the perilymph could be noticed. Hair cell damages at the organ of corti could in no case be observed."}
{"id": "PMID:236743", "title": "Effect of hyperbaric air on long-term memory organization and recall.", "content": "Three experiments are reported which investigated the effects of hyperbaric air on long-term memory. In the first, word lists were learned at 1 and 8.6 ATA using a variable input-free recall paradigm. It was found that learning was affected but not clustered memory organization, and it was concluded that disorganization of memory is not a factor contributing to the learning deficit found with hyperbaric air. In the second and third experiments it was found that the recall of words, which had been learned when non-narcotic, was disrupted at 10 ATA by hyperbaric air and that this disruption was not overcome by providing memory-cues at the time of recall. Two possible explanations for these results are discussed. A hypothesis is put forward to reconcile the results of various hyperbaric memory experiments by pointing out that a relationship between stress and learning found with nitrous oxide could be applicable to these studies also.", "contents": "Effect of hyperbaric air on long-term memory organization and recall. Three experiments are reported which investigated the effects of hyperbaric air on long-term memory. In the first, word lists were learned at 1 and 8.6 ATA using a variable input-free recall paradigm. It was found that learning was affected but not clustered memory organization, and it was concluded that disorganization of memory is not a factor contributing to the learning deficit found with hyperbaric air. In the second and third experiments it was found that the recall of words, which had been learned when non-narcotic, was disrupted at 10 ATA by hyperbaric air and that this disruption was not overcome by providing memory-cues at the time of recall. Two possible explanations for these results are discussed. A hypothesis is put forward to reconcile the results of various hyperbaric memory experiments by pointing out that a relationship between stress and learning found with nitrous oxide could be applicable to these studies also."}
{"id": "PMID:236763", "title": "Epidural analgesia, fetal monitoring and the condition of the baby at birth with breech presentation.", "content": "Between December 1970 and March 1973, 138 patients with a singleton fetus presenting by the breech after 36 weeks of pregnancy were deemed suitable for vaginal delivery under epidural analgesia; 130 were delivered vaginally, 10 of them by breech extraction. There was one stillbirth and no neonatal deaths. Epidural analgesia for vaginal breech delivery seemed beneficial. In 65 cases it was possible to compare the umbilical vein pH with the Apgar score at one minute. In 35 patients a continuous recording of the fetal heart rate was used to predict the Apgar score at one minute and the results are discussed.", "contents": "Epidural analgesia, fetal monitoring and the condition of the baby at birth with breech presentation. Between December 1970 and March 1973, 138 patients with a singleton fetus presenting by the breech after 36 weeks of pregnancy were deemed suitable for vaginal delivery under epidural analgesia; 130 were delivered vaginally, 10 of them by breech extraction. There was one stillbirth and no neonatal deaths. Epidural analgesia for vaginal breech delivery seemed beneficial. In 65 cases it was possible to compare the umbilical vein pH with the Apgar score at one minute. In 35 patients a continuous recording of the fetal heart rate was used to predict the Apgar score at one minute and the results are discussed."}
{"id": "PMID:236764", "title": "NAD- and NADP-dependent 7alpha-hydroxysteroid dehydrogenases from bacteroides fragilis.", "content": "Twenty strains of Bacteroides fragilis were screened for hydroxysteroid oxidoreductase activity in cell-free preparations. Eighteen strains were shown  to contain NAD-dependent 7alpha-hydroxysteroid dehydrogenase. Sixteen of the strains containing the NAD-dependent enzyme also contained NADP-depedent 7alpha-hydroxysteroid dehydrogenase, but invariably in lesser amounts. A strain particulary rich in both 7alpha-hydroxysteroid dehydrogenase activities was selected for further study. Measurement of activity as a function of pH revealed a fairly sharp optimal activity range of 9.5--10.0 for the NAD-dependent enzyme and a broad flat optimal range of 7.0--9.0 for the NADP-dependent enzyme. Michaelis constants for trihydroxy-bile acids for the NAD-dependent enzyme were in the range of 0.32--0.34 mM, whereas dihydroxy-bile acids gave a Km of 0.1 mM. Thin-layer chromatography studies on the oxidation product of 3alpha, 7alpha-dihydroxy-5beta-cholanoic acid (chenodeoxycholic acid) by the dehydrogenase revealed a band corresponding to that of synthetic 3alpha-hydroxy, 7-keto-5beta-cholanoic acid. Similarly the oxidation product of chenodeoxycholic acid by both 7alpha-hydroxysteroid dehydrogenase and commercially available 3alpha-hy-droxysteroid dehydrogenase revealed a band corresponding to that of synthetic 3,7-diketo-5beta-cholanoic acid. Neither of these two oxidation products could be distinguished from those by the Escherichia coli dehydrogenase oxidation previously reported. Disc-gel electrophoresis of a cell-free lyophilized preparation indicated one active band for NAD-dependent activity of mobility similar to that for the NADP-dependent E. coli enzyme. The NADP-dependent dehydrogenase was unstable and rapidly lost activity after polyacylamide disc-gel electrophoresis, ultracentrifugation, freezing on refrigeration at 4 degrees C. No 3 alpha- or 12alpha-oriented oxidoreductase activity was demonstrated in any of the strains examined.", "contents": "NAD- and NADP-dependent 7alpha-hydroxysteroid dehydrogenases from bacteroides fragilis. Twenty strains of Bacteroides fragilis were screened for hydroxysteroid oxidoreductase activity in cell-free preparations. Eighteen strains were shown  to contain NAD-dependent 7alpha-hydroxysteroid dehydrogenase. Sixteen of the strains containing the NAD-dependent enzyme also contained NADP-depedent 7alpha-hydroxysteroid dehydrogenase, but invariably in lesser amounts. A strain particulary rich in both 7alpha-hydroxysteroid dehydrogenase activities was selected for further study. Measurement of activity as a function of pH revealed a fairly sharp optimal activity range of 9.5--10.0 for the NAD-dependent enzyme and a broad flat optimal range of 7.0--9.0 for the NADP-dependent enzyme. Michaelis constants for trihydroxy-bile acids for the NAD-dependent enzyme were in the range of 0.32--0.34 mM, whereas dihydroxy-bile acids gave a Km of 0.1 mM. Thin-layer chromatography studies on the oxidation product of 3alpha, 7alpha-dihydroxy-5beta-cholanoic acid (chenodeoxycholic acid) by the dehydrogenase revealed a band corresponding to that of synthetic 3alpha-hydroxy, 7-keto-5beta-cholanoic acid. Similarly the oxidation product of chenodeoxycholic acid by both 7alpha-hydroxysteroid dehydrogenase and commercially available 3alpha-hy-droxysteroid dehydrogenase revealed a band corresponding to that of synthetic 3,7-diketo-5beta-cholanoic acid. Neither of these two oxidation products could be distinguished from those by the Escherichia coli dehydrogenase oxidation previously reported. Disc-gel electrophoresis of a cell-free lyophilized preparation indicated one active band for NAD-dependent activity of mobility similar to that for the NADP-dependent E. coli enzyme. The NADP-dependent dehydrogenase was unstable and rapidly lost activity after polyacylamide disc-gel electrophoresis, ultracentrifugation, freezing on refrigeration at 4 degrees C. No 3 alpha- or 12alpha-oriented oxidoreductase activity was demonstrated in any of the strains examined."}
{"id": "PMID:236759", "title": "Current concepts of the mechanism of acute inflammation in gouty arthritis.", "content": "The acute gouty attack develops after free crystalline monosodium urate crystals appear in the joint cavity (1). Recent developments in the investigation of urate crystal-induced inflammation have led to a better understanding of the pathogenesis of acute gouty arthritis. The purpose of this review is to summarize present concepts concerning the mechanism of the acute gouty attack.", "contents": "Current concepts of the mechanism of acute inflammation in gouty arthritis. The acute gouty attack develops after free crystalline monosodium urate crystals appear in the joint cavity (1). Recent developments in the investigation of urate crystal-induced inflammation have led to a better understanding of the pathogenesis of acute gouty arthritis. The purpose of this review is to summarize present concepts concerning the mechanism of the acute gouty attack."}
{"id": "PMID:236765", "title": "Purification and properties of a lipid acyl-hydrolase from potato tubers.", "content": "1. A pure lipid acyl-hydrolase was prepared from potato tubers by acetone precipitation, Sephadex G-100 and DEAE-Sephadex A-50 column chromatography, and by electrofocusing. 2. The purified enzyme was an acidic protein of pI 5.0 and molecular weight of about 70 000. Km values were 0.38 mM for monogalactosyldiacylglycerol and 1.7 mM for phosphatidylcholine. 3. The hydrolytic activity of the enzyme on different substrates was determined. The relative rates were acylsterylglucoside  greater than monogalactosyldiacylglycerol greater than monogalactosylmonoacylglycerol greater than digalactosyldiacylglycerol greater than diagalactosylmonoacylglycerol, while the rates for phospholipids were lysophosphatidylcholine greater than phosphatidylcholine greater than lysophosphatidylethanolamine greater than phosphatidylethanolamine. 4. Analyses of enzymatic hydrolysis products suggested that a single enzyme had both galactolipase and phospholipase activities, and for the phospholipids it showed activities similar to phospholipase B and glycerylphosphorylcholine diesterase. 5. A competitive relation was found between monogalactosyldiacylglycerol and phosphatidylcholine as substrates of the enzyme, indicating that the active sites for both substrates may be the same. 6. It was suggested that histidine and probably serine residues were important to the enzymic activity, and that a tyrosine residue might be involved in the activity as an accessory component.", "contents": "Purification and properties of a lipid acyl-hydrolase from potato tubers. 1. A pure lipid acyl-hydrolase was prepared from potato tubers by acetone precipitation, Sephadex G-100 and DEAE-Sephadex A-50 column chromatography, and by electrofocusing. 2. The purified enzyme was an acidic protein of pI 5.0 and molecular weight of about 70 000. Km values were 0.38 mM for monogalactosyldiacylglycerol and 1.7 mM for phosphatidylcholine. 3. The hydrolytic activity of the enzyme on different substrates was determined. The relative rates were acylsterylglucoside  greater than monogalactosyldiacylglycerol greater than monogalactosylmonoacylglycerol greater than digalactosyldiacylglycerol greater than diagalactosylmonoacylglycerol, while the rates for phospholipids were lysophosphatidylcholine greater than phosphatidylcholine greater than lysophosphatidylethanolamine greater than phosphatidylethanolamine. 4. Analyses of enzymatic hydrolysis products suggested that a single enzyme had both galactolipase and phospholipase activities, and for the phospholipids it showed activities similar to phospholipase B and glycerylphosphorylcholine diesterase. 5. A competitive relation was found between monogalactosyldiacylglycerol and phosphatidylcholine as substrates of the enzyme, indicating that the active sites for both substrates may be the same. 6. It was suggested that histidine and probably serine residues were important to the enzymic activity, and that a tyrosine residue might be involved in the activity as an accessory component."}
{"id": "PMID:236761", "title": "Elevation of arterial phosphorfuctokinase activity associated with susceptibility to atherosclerosis in pigeons.", "content": "The activity of phosphofructokinase (PFK, 2.7.1.11) was measured in arteries of very young (5-8 week old) pigeons known to differ in susceptibility to atherosclerosis. The activity of the arterial enzyme was significantly higher in the atherosclerosis-susceptible White Carneau (WC) pigeons than in the resistant Show Racers (SR). The difference was significant whether enzyme activity was calculated on the basis of extract protein, DNA content or fat-free dry weight. In the White Carneau arteries the activity of the enzyme was higher in the female than the male pigeons. PFK is a key regulatory enzyme of glycolysis and is subject to fine control adjustments. A low ATP/ADP ratio and a fall in citrate concentration, as for example, induced by hypoxia, are meditors of a feedback mechanism leading to a rise in PFK activity and enhancement of glycolysis for energy production. This mechanism appears to be the cause of the higher PFK activity in the WC arteries, because related studies indicate impaired Krebs cycle activity in these vessels. It is suggested that the increased dependence of the WC arteries on glycolysis facilitates the development of atherosclerosis in this pigeon strain and that the mechanism is similar to the mechanism by which tissue hypoxia causes lipid accumulation and connective tissue alterations in the arterial wall.", "contents": "Elevation of arterial phosphorfuctokinase activity associated with susceptibility to atherosclerosis in pigeons. The activity of phosphofructokinase (PFK, 2.7.1.11) was measured in arteries of very young (5-8 week old) pigeons known to differ in susceptibility to atherosclerosis. The activity of the arterial enzyme was significantly higher in the atherosclerosis-susceptible White Carneau (WC) pigeons than in the resistant Show Racers (SR). The difference was significant whether enzyme activity was calculated on the basis of extract protein, DNA content or fat-free dry weight. In the White Carneau arteries the activity of the enzyme was higher in the female than the male pigeons. PFK is a key regulatory enzyme of glycolysis and is subject to fine control adjustments. A low ATP/ADP ratio and a fall in citrate concentration, as for example, induced by hypoxia, are meditors of a feedback mechanism leading to a rise in PFK activity and enhancement of glycolysis for energy production. This mechanism appears to be the cause of the higher PFK activity in the WC arteries, because related studies indicate impaired Krebs cycle activity in these vessels. It is suggested that the increased dependence of the WC arteries on glycolysis facilitates the development of atherosclerosis in this pigeon strain and that the mechanism is similar to the mechanism by which tissue hypoxia causes lipid accumulation and connective tissue alterations in the arterial wall."}
{"id": "PMID:236766", "title": "Cholesterol ester hydrolase in human red blood cells.", "content": "1. Cholesterol ester hydrolytic activity (sterol-ester hydrolase EC 3.1.1.13) was detected in human red blood cells. Enzyme activity appeared confined to the cell membrane and was most marked in washed preparations of red cell ghosts. 2. Hydrolytic activity was stimulated by the anti-oxidants D-alpha-tocopherol and butylated hydroxytoluene. Marked inhibition was produced by erythrocyte hemolysate, sodium taurocholate, and Triton X-100. 3. Optimal pH for the reaction was 5.4--5.7. 4. Because red cell cholesterol is all unesterified, it is speculated that the hydrolase serves to maintain the erythrocyte membrane free of esterified cholesterol.", "contents": "Cholesterol ester hydrolase in human red blood cells. 1. Cholesterol ester hydrolytic activity (sterol-ester hydrolase EC 3.1.1.13) was detected in human red blood cells. Enzyme activity appeared confined to the cell membrane and was most marked in washed preparations of red cell ghosts. 2. Hydrolytic activity was stimulated by the anti-oxidants D-alpha-tocopherol and butylated hydroxytoluene. Marked inhibition was produced by erythrocyte hemolysate, sodium taurocholate, and Triton X-100. 3. Optimal pH for the reaction was 5.4--5.7. 4. Because red cell cholesterol is all unesterified, it is speculated that the hydrolase serves to maintain the erythrocyte membrane free of esterified cholesterol."}
{"id": "PMID:236767", "title": "Nicotinamide-adenine dinucleotide inhibition of pig kidney alkaline phosphatase.", "content": "1. The interaction of NAD+, NADH and various nucleotide analogues with pig kidney alkaline phosphatase (orthophosphoric-monoester phosphohydrolase (alkaline optimum) EC 3.1.3.1) has been investigated by kinetic means. Some inhibitors act uncompetitively whereas others markedly increase the slopes of double reciprocal plots suggesting they have some affinity for the free enzyme. 2. The compounds seem to bind to alkaline phosphatase through interactions of their bases with a relatively non-specific region of the enzyme, although it is likely that for those nucleotides having some affinity for the free enzyme there is some attraction between the pyrophosphate backbone and the active site. 3. From studies of the effect of NAD+ and NADH on ATPase activity it was concluded that the substrate inhibition that is characteristic of the ATPase activity of alkaline phosphatase originates from binding of ATP to the site assumed to exist for NAD+ and NADH. The potentiation of NAD+-inhibition of ATPase activity by Mg-2+ is probably a result of the depletion of [ATP-4-] the true substrate. The depletion allows NAD+ to complete more effectively for the active site. 4. Binding of NADH is favoured by protonation of an enzymic group with a pK of approx. 9.0 belonging possibly to a tyrosine residue or a zinc hydrate. 5. A large entropy decrease was found to accompany the binding of NAD+ and NADH to alkaline phosphatase. This may be further evidence of an \"induced-fit\" mechanism previously suspected because of the synergistic inhibitory effects of adenosine and nicotinamide.", "contents": "Nicotinamide-adenine dinucleotide inhibition of pig kidney alkaline phosphatase. 1. The interaction of NAD+, NADH and various nucleotide analogues with pig kidney alkaline phosphatase (orthophosphoric-monoester phosphohydrolase (alkaline optimum) EC 3.1.3.1) has been investigated by kinetic means. Some inhibitors act uncompetitively whereas others markedly increase the slopes of double reciprocal plots suggesting they have some affinity for the free enzyme. 2. The compounds seem to bind to alkaline phosphatase through interactions of their bases with a relatively non-specific region of the enzyme, although it is likely that for those nucleotides having some affinity for the free enzyme there is some attraction between the pyrophosphate backbone and the active site. 3. From studies of the effect of NAD+ and NADH on ATPase activity it was concluded that the substrate inhibition that is characteristic of the ATPase activity of alkaline phosphatase originates from binding of ATP to the site assumed to exist for NAD+ and NADH. The potentiation of NAD+-inhibition of ATPase activity by Mg-2+ is probably a result of the depletion of [ATP-4-] the true substrate. The depletion allows NAD+ to complete more effectively for the active site. 4. Binding of NADH is favoured by protonation of an enzymic group with a pK of approx. 9.0 belonging possibly to a tyrosine residue or a zinc hydrate. 5. A large entropy decrease was found to accompany the binding of NAD+ and NADH to alkaline phosphatase. This may be further evidence of an \"induced-fit\" mechanism previously suspected because of the synergistic inhibitory effects of adenosine and nicotinamide."}
{"id": "PMID:236768", "title": "Purification of a derepressible arylsulfatase from Chlamydomonas reinhardti. Properties of the enzyme in intact cells and in purified state.", "content": "Arylsulfatase (aryl-sulfate sulfohdydrolase, EC 3.1.6.1) has been purified from SO4-2-minus-starved cells of Chlamydomonas reinhardti. The enzyme was isolated from acetone-powder extract by (NH4)2SO4 precipitation, Sephadex G-200 filtration and ion-exchange chromatography. Only one fraction of aryl-sulfatase was found. The final preparation was homogenous by the criteria of sedimentation, diffusion and polyacrylamide gel electrophoresis. The purified enzyme had a molecular weight of about 150 000, estimated by ultracentrifugation and gel filtration, and an isoelectric point of 9.0. The properties of the enzyme as investigated in intact cells and in the purified state were found to be very similar except for the temperature optimum. Imidazole strongly increased the enzyme by increasing the V, but reduced the affinity for the substrate. The enzyme activity was competitively inhibited by borate with a greater affinity for borate than for the substrate. The Chlamydomonas enzyme is a Type I arylsulfatase since it was inhibited by CN-minus, but not SO4-2-minus and phosphate.", "contents": "Purification of a derepressible arylsulfatase from Chlamydomonas reinhardti. Properties of the enzyme in intact cells and in purified state. Arylsulfatase (aryl-sulfate sulfohdydrolase, EC 3.1.6.1) has been purified from SO4-2-minus-starved cells of Chlamydomonas reinhardti. The enzyme was isolated from acetone-powder extract by (NH4)2SO4 precipitation, Sephadex G-200 filtration and ion-exchange chromatography. Only one fraction of aryl-sulfatase was found. The final preparation was homogenous by the criteria of sedimentation, diffusion and polyacrylamide gel electrophoresis. The purified enzyme had a molecular weight of about 150 000, estimated by ultracentrifugation and gel filtration, and an isoelectric point of 9.0. The properties of the enzyme as investigated in intact cells and in the purified state were found to be very similar except for the temperature optimum. Imidazole strongly increased the enzyme by increasing the V, but reduced the affinity for the substrate. The enzyme activity was competitively inhibited by borate with a greater affinity for borate than for the substrate. The Chlamydomonas enzyme is a Type I arylsulfatase since it was inhibited by CN-minus, but not SO4-2-minus and phosphate."}
{"id": "PMID:236769", "title": "Proteolytic activities in yeast.", "content": "Studies on the mechanism and time course of the activation of proteinases A (EC 3.4.23.8), B (EC 3.4.22.9) and C (EC 3.4.12.--) in crude yeast extracts at pH 5.1 and 25 degrees C showed that the increase in proteinase B activity is paralleled with the disappearance of proteinase B inhibitor. Addition of purified proteinase A to fresh crude extracts accelerates the inactivation of the proteinase B inhibitor and the appearance of maximal activities of proteinases B and C. The decrease of proteinase B inhibitor activity and the increase of proteinase B activity are markedly retarded by the addition of pepstatin. Because 10-minus 7 M pepstatin completely inhibits proteinase A without affecting proteinase B activity, this is another indication for the role of proteinase A during the activation of proteinase B. Whereas extracts of yeast grown on minimal medium reached maximal activation of proteinases B and C after 20 h of incubation at pH 5.1 and 25 degrees C, extracts of yeast grown on complete medium had to be incubated for about 100 h. In the latter case, the addition of proteinas A results in maximal activation of proteinases B and C and disappearance of proteinase B inhibitor activity only after 10--20 h of incubation. With the optimal conditions, the maximal activities of proteinases A, B and C, as well as of the proteinase B inhibitor, were determined in crude extracts of yeast that had been grown batchwise for different lengths of time either on minimal or on complete medium. Upon incubation, all three proteinases were activated by several times their initial activity. This reflects the existence of proteolytically degradable inhibitors of the three proteinases and together with the above mentioned observations it demonstrates that the \"activation\" of yeast proteinases A, B and C upon incubation results from the proteolytic digestion of inhibitors rather than from activation of inactive zymogens by limited proteolysis.", "contents": "Proteolytic activities in yeast. Studies on the mechanism and time course of the activation of proteinases A (EC 3.4.23.8), B (EC 3.4.22.9) and C (EC 3.4.12.--) in crude yeast extracts at pH 5.1 and 25 degrees C showed that the increase in proteinase B activity is paralleled with the disappearance of proteinase B inhibitor. Addition of purified proteinase A to fresh crude extracts accelerates the inactivation of the proteinase B inhibitor and the appearance of maximal activities of proteinases B and C. The decrease of proteinase B inhibitor activity and the increase of proteinase B activity are markedly retarded by the addition of pepstatin. Because 10-minus 7 M pepstatin completely inhibits proteinase A without affecting proteinase B activity, this is another indication for the role of proteinase A during the activation of proteinase B. Whereas extracts of yeast grown on minimal medium reached maximal activation of proteinases B and C after 20 h of incubation at pH 5.1 and 25 degrees C, extracts of yeast grown on complete medium had to be incubated for about 100 h. In the latter case, the addition of proteinas A results in maximal activation of proteinases B and C and disappearance of proteinase B inhibitor activity only after 10--20 h of incubation. With the optimal conditions, the maximal activities of proteinases A, B and C, as well as of the proteinase B inhibitor, were determined in crude extracts of yeast that had been grown batchwise for different lengths of time either on minimal or on complete medium. Upon incubation, all three proteinases were activated by several times their initial activity. This reflects the existence of proteolytically degradable inhibitors of the three proteinases and together with the above mentioned observations it demonstrates that the \"activation\" of yeast proteinases A, B and C upon incubation results from the proteolytic digestion of inhibitors rather than from activation of inactive zymogens by limited proteolysis."}
{"id": "PMID:236770", "title": "Properties and specificity of the major metal-chelator-sensitive proteinase in the keratinolytic larvae of the webbing clothes moth.", "content": "The metal chelator-sensitive proteinase activity from the larvae of the webbing clothes moth, Tineola bisselliella, was fractionated into two components by chromatography on DEAE-cellulose and the properties of the major fraction investigated. The approximate molecular weight obtained by gel filtration was 24 000. The pH optimum of 9.4 and the high stability between pH 9.0 and 11.5 are consistent with the alkaline conditions known to be present in the larval mid-gut. The enzyme also showed a second region of high stability around pH 2.3. The cleavage specificity against S-carboxy-methyl A and B chains of insulin was quite different to that of the metal chelator-sensitive proteinases from snake venoms and microorganisms. 10 bonds in the A-chain and 8 bonds in the B-chain were cleaved and the tentative rules governing the specificity limitations of this metal-chelator-sensitive proteinase are discussed.", "contents": "Properties and specificity of the major metal-chelator-sensitive proteinase in the keratinolytic larvae of the webbing clothes moth. The metal chelator-sensitive proteinase activity from the larvae of the webbing clothes moth, Tineola bisselliella, was fractionated into two components by chromatography on DEAE-cellulose and the properties of the major fraction investigated. The approximate molecular weight obtained by gel filtration was 24 000. The pH optimum of 9.4 and the high stability between pH 9.0 and 11.5 are consistent with the alkaline conditions known to be present in the larval mid-gut. The enzyme also showed a second region of high stability around pH 2.3. The cleavage specificity against S-carboxy-methyl A and B chains of insulin was quite different to that of the metal chelator-sensitive proteinases from snake venoms and microorganisms. 10 bonds in the A-chain and 8 bonds in the B-chain were cleaved and the tentative rules governing the specificity limitations of this metal-chelator-sensitive proteinase are discussed."}
{"id": "PMID:236771", "title": "Isolation of an extracellular neutral proteinase from Pseudomonas fragi.", "content": "A single proteolytic enzyme (EC 3.4.4.-) was isolated from culture supernatants of Pseudomonas fragi with 20% yielded and 60-fold purification by means of stepwise DEAE-Sephadex batch adsorption, ammonium sulfate precipitation, gel filtration and DEAE-cellulose chromatography. The enzyme was Zn-2+ activated and Ca-2+ stabilized, had optimum activity at pH 6.5--8.0 and 40 degrees C. The molecular weight range was 40 000--50 000 as determined by dodecylsulfate  gel electrophoresis, gel filtration and Zn assay. This proteinase has properties similar to other extracellular bacterial neutral proteinases.", "contents": "Isolation of an extracellular neutral proteinase from Pseudomonas fragi. A single proteolytic enzyme (EC 3.4.4.-) was isolated from culture supernatants of Pseudomonas fragi with 20% yielded and 60-fold purification by means of stepwise DEAE-Sephadex batch adsorption, ammonium sulfate precipitation, gel filtration and DEAE-cellulose chromatography. The enzyme was Zn-2+ activated and Ca-2+ stabilized, had optimum activity at pH 6.5--8.0 and 40 degrees C. The molecular weight range was 40 000--50 000 as determined by dodecylsulfate  gel electrophoresis, gel filtration and Zn assay. This proteinase has properties similar to other extracellular bacterial neutral proteinases."}
{"id": "PMID:236772", "title": "Kinetic studies of a beta-lactamase by a computerized microacidimetric method.", "content": "On-line computerized treatment of enzyme kinetic data allows the precise measurement of Michaelis--Menten constants (Km and V) from a single progress curve. This method has been used to determine the kinetic constants of a beta-lactamase extracted from an Escherichia coli strain. In the profile of enzymatic activity there obtained, Km and V are a function of the pH. From these results some information is derived about the mechanism of the enzyme--substrate binding.", "contents": "Kinetic studies of a beta-lactamase by a computerized microacidimetric method. On-line computerized treatment of enzyme kinetic data allows the precise measurement of Michaelis--Menten constants (Km and V) from a single progress curve. This method has been used to determine the kinetic constants of a beta-lactamase extracted from an Escherichia coli strain. In the profile of enzymatic activity there obtained, Km and V are a function of the pH. From these results some information is derived about the mechanism of the enzyme--substrate binding."}
{"id": "PMID:236773", "title": "Functionally distinct classes of K+ sites on the (Na+ + K+)-dependent ATPase.", "content": "K+ interactions with a rat brain (Na+ + K+)-dependent ATPase and the associated K+-dependent nitrophenyl phosphatase activity were examined. Classes of sites for K+ were distinguished, initially, on the basis of affinity estimated by kinetic analysis in terms of KO.5 (the concentration for half-maximal activation), and by K+-accelerated enzyme inactivation by F-minus, which permits evaluation of a dissociation constant for K+, KD. Moderate-affinity sites (\"alpha sites\"), with a KD near 1 mM, were demonstrable for the phosphatase activity and for the \"free\" enzyme. High-affinity sites (\"beta sites\"), with a KD near 0.1 mM, were seen for the overall ATPase activity and under conditions in which enzyme phosphorylation by substrate also occurs. Further differentiation between alpha and beta sites was made in terms of (i) the characteristic changes in affinity with pH, and (ii) the efficacy of Li+ relative to K+, Rb+, Cs+, and Tl+ at these two classes of sites. Low-affinity sites (\"gamma sites\") through which K+ inhibits enzymatic activity were also detectable, with a KD around 140 mM. These data are incorporated into a model for the reaction sequence to accommodate both transport processes and certain K+/ATP antagonisms.", "contents": "Functionally distinct classes of K+ sites on the (Na+ + K+)-dependent ATPase. K+ interactions with a rat brain (Na+ + K+)-dependent ATPase and the associated K+-dependent nitrophenyl phosphatase activity were examined. Classes of sites for K+ were distinguished, initially, on the basis of affinity estimated by kinetic analysis in terms of KO.5 (the concentration for half-maximal activation), and by K+-accelerated enzyme inactivation by F-minus, which permits evaluation of a dissociation constant for K+, KD. Moderate-affinity sites (\"alpha sites\"), with a KD near 1 mM, were demonstrable for the phosphatase activity and for the \"free\" enzyme. High-affinity sites (\"beta sites\"), with a KD near 0.1 mM, were seen for the overall ATPase activity and under conditions in which enzyme phosphorylation by substrate also occurs. Further differentiation between alpha and beta sites was made in terms of (i) the characteristic changes in affinity with pH, and (ii) the efficacy of Li+ relative to K+, Rb+, Cs+, and Tl+ at these two classes of sites. Low-affinity sites (\"gamma sites\") through which K+ inhibits enzymatic activity were also detectable, with a KD around 140 mM. These data are incorporated into a model for the reaction sequence to accommodate both transport processes and certain K+/ATP antagonisms."}
{"id": "PMID:236774", "title": "Rat liver cysteine sulfinate decarboxylase: purification, new appraisal of the molecular weight and determination of catalytic properties.", "content": "Rat liver cystein sulfinate decarboxylase (L-cystein sulfinate carboxylase) was purified approximately 500-fold. By cellulose acetate and polyacrylamide gel electrophoresis or by analytical ultracentrifugation, the purified enzyme appears to be nearly homogeneous. The Stokes radius (3.4 nm) and sedimentation coefficient (6.5 S) were determined. The molecular weight, calculated and experimentally estimated is around 100 000 and the enzyme is constituted of two identical subunits whose molecular weights are 55 000. The role of pyridoxal phosphate as coenzyme was demonstrated and the requirement for free sulhydryl groups for activity was studied. The ability of native pure cysteine sulfinate decarboxylase to also decarboxylate cysteate was stressed: therefore, we concluded that in rat liver a single protein catalyzed both reactions, although only the decarboxylation of cysteine sulfinate is of physiological interest.", "contents": "Rat liver cysteine sulfinate decarboxylase: purification, new appraisal of the molecular weight and determination of catalytic properties. Rat liver cystein sulfinate decarboxylase (L-cystein sulfinate carboxylase) was purified approximately 500-fold. By cellulose acetate and polyacrylamide gel electrophoresis or by analytical ultracentrifugation, the purified enzyme appears to be nearly homogeneous. The Stokes radius (3.4 nm) and sedimentation coefficient (6.5 S) were determined. The molecular weight, calculated and experimentally estimated is around 100 000 and the enzyme is constituted of two identical subunits whose molecular weights are 55 000. The role of pyridoxal phosphate as coenzyme was demonstrated and the requirement for free sulhydryl groups for activity was studied. The ability of native pure cysteine sulfinate decarboxylase to also decarboxylate cysteate was stressed: therefore, we concluded that in rat liver a single protein catalyzed both reactions, although only the decarboxylation of cysteine sulfinate is of physiological interest."}
{"id": "PMID:236775", "title": "19-F NMR studies of the binding of a  fluorine-labeled phosphonate ion to E. coli alkaline phosphatase.", "content": "The interaction of a fluorinated phosphonate with Zn-2+-and Mn-2+-alkaline phosphatase as studied by 19-F NMR revealed a stoichiometry of 1:1 for the binding of the phosphonate anion to the enzyme. In the presence of two metal ions, one fluorinated phosphonate ion was found to interact strongly with the enzyme, while a different interaction was observed when the number of metal ions per enzyme exceeded two. Phosphate replaced enzyme bound phosphonate, as is shown by the 19-F NMR spectra. No direct interaction between the fluorinated phosphonate and the metal ion responsible for enzyme activity was indicated by the 19-F NMR data. This observation supports the idea of a considerable distance between metal ion and substrate binding site in Escherichia coli alkaline phosphatase.", "contents": "19-F NMR studies of the binding of a  fluorine-labeled phosphonate ion to E. coli alkaline phosphatase. The interaction of a fluorinated phosphonate with Zn-2+-and Mn-2+-alkaline phosphatase as studied by 19-F NMR revealed a stoichiometry of 1:1 for the binding of the phosphonate anion to the enzyme. In the presence of two metal ions, one fluorinated phosphonate ion was found to interact strongly with the enzyme, while a different interaction was observed when the number of metal ions per enzyme exceeded two. Phosphate replaced enzyme bound phosphonate, as is shown by the 19-F NMR spectra. No direct interaction between the fluorinated phosphonate and the metal ion responsible for enzyme activity was indicated by the 19-F NMR data. This observation supports the idea of a considerable distance between metal ion and substrate binding site in Escherichia coli alkaline phosphatase."}
{"id": "PMID:236776", "title": "Electron donors and inhibitors of nitrate reductase from Cyanidium caldarium.", "content": "Studies on nitrate reductase (NAD(P)H:nitrate oxidoreductases EC 1.6.6.2) of Cyanidium caldarium revealed that the enzyme is inhibited by excess of electron donor, NADPH, reduced benzylviologen and FMN. Also dithionite, used to reduce benzylviologen and FMN, inactivates nitrate reductase: however, FMN at an optimal concentration and nitrate, added before the dithionite, protect the enzyme against this inactivation. Cyanide, cyanate and carbamyl phosphate inhibit the enzyme competitively with respect to nitrate, and Ki values are reported. Organic mercurials, 0.1 mM, act preferentially on NADPH activity, whereas Ag+ and Hg-2+ at the same concentration inactivate 80--90% of the benzylviologen and FMN activities. ADP is very poor inhibitor. Urea 4 M in 2 h destroys 90% of the NADPH activity and only 30% of the benzylviologen and FMN activities. The apparent Km values for NADPH, benzylviologen, FMN and nitrate have been determined.", "contents": "Electron donors and inhibitors of nitrate reductase from Cyanidium caldarium. Studies on nitrate reductase (NAD(P)H:nitrate oxidoreductases EC 1.6.6.2) of Cyanidium caldarium revealed that the enzyme is inhibited by excess of electron donor, NADPH, reduced benzylviologen and FMN. Also dithionite, used to reduce benzylviologen and FMN, inactivates nitrate reductase: however, FMN at an optimal concentration and nitrate, added before the dithionite, protect the enzyme against this inactivation. Cyanide, cyanate and carbamyl phosphate inhibit the enzyme competitively with respect to nitrate, and Ki values are reported. Organic mercurials, 0.1 mM, act preferentially on NADPH activity, whereas Ag+ and Hg-2+ at the same concentration inactivate 80--90% of the benzylviologen and FMN activities. ADP is very poor inhibitor. Urea 4 M in 2 h destroys 90% of the NADPH activity and only 30% of the benzylviologen and FMN activities. The apparent Km values for NADPH, benzylviologen, FMN and nitrate have been determined."}
{"id": "PMID:236777", "title": "Purification, properties and induction of a specific benzoate-4-hydroxylase from Aspergillus niger (UBC 814).", "content": "An inducible benzoate-4-hydroxylase has been partially purified from crude extracts of the mycelial felts of Aspergillus niger. This enzyme catalyzes the transformation of benzoate to p-hydroxybenzoate with equimolar consumption of NADPH and O2. It requires tetrahydropteridine as a prosthetic group. The optimum activity was found at pH 6.2 with a Km value at 30 degrees C of 1.6-10-minus 4 for NADPH and 1.3-10-minus 4 M for benzoate. Fe-2+ (iron) is required for the enzyme activity. The enzyme is stabilized by the inclusion of benzoate, EDTA and glutathione in the extracting buffer. The enzyme is specific for benzoate as substrate. Sulfhydryl groups(s) are essential for enzyme activity as indicated by p-chloromercuri-benzoate and N-ethylmaleimide inactivation. Benzoate-4-hydroxylase activity is decreased in the mycelial felts of Aspergillus niger grown in the presence of higher concentrations of benzoate. Maximum activity of the enzyme was observed at 36 h after inoculation.", "contents": "Purification, properties and induction of a specific benzoate-4-hydroxylase from Aspergillus niger (UBC 814). An inducible benzoate-4-hydroxylase has been partially purified from crude extracts of the mycelial felts of Aspergillus niger. This enzyme catalyzes the transformation of benzoate to p-hydroxybenzoate with equimolar consumption of NADPH and O2. It requires tetrahydropteridine as a prosthetic group. The optimum activity was found at pH 6.2 with a Km value at 30 degrees C of 1.6-10-minus 4 for NADPH and 1.3-10-minus 4 M for benzoate. Fe-2+ (iron) is required for the enzyme activity. The enzyme is stabilized by the inclusion of benzoate, EDTA and glutathione in the extracting buffer. The enzyme is specific for benzoate as substrate. Sulfhydryl groups(s) are essential for enzyme activity as indicated by p-chloromercuri-benzoate and N-ethylmaleimide inactivation. Benzoate-4-hydroxylase activity is decreased in the mycelial felts of Aspergillus niger grown in the presence of higher concentrations of benzoate. Maximum activity of the enzyme was observed at 36 h after inoculation."}
{"id": "PMID:236778", "title": "Effects of sulfhydryl agents on the activation of tryptophan-5-monooxygenase from bovine pineal glands.", "content": "Partially purified tryptophan-5-monooxygenase (L-tryptophan, tetrahydropteridine: oxygen oxidoreductase (5-hydroxylating) EC 1.14.16.4)from bovine pineal gland was activated by preincubation with sulfhydryl agents such as dithiothreitol, L-cysteine, cysteamine, L-cysteine ethylester, N-acetyl-L-cysteine, 2-mercaptoethanol and reduced glutathione, at alkaline pH (optimum pH equals 8.5). Dithiothreitol was the most effective of these, leading to approximately 50-fold activation of the enzyme after preincubation. Fe-2+ or other reducing agents such as borohydride, dithionite and ascorbate facilitated the velocity of the activation in the presence of sulfhydryl agents. In the absence of sulfhydryl agents, no activation was observed even in the presence of Fe-2+ or other reducing agents, suggesting an obligatory role or sulhydryl agents during the activation. The relative velocity and full extent of the activation were dependent on the concentrations of both the sulfhydryl agent and the enzyme in the activation mixture. The kinetic analysis of the activation indicated that the sulfhydryl agent reacts with more than 2 sites in the enzyme; one type of site is reduced by sulfhydryl agents, Fe-2+ or other reducing agents and the other specifically modified by a sulfhydryl agent. The activated enzyme did not require any exogenous Fe-2+ for its catalytic activity, but some roles of iron maybe exist in its catalytic reaction. The optimum pH for catalytic reaction of the activated enzyme was approximately 6.5. The apparent Km for L-tryptophan and pteridine cofactor, tetrahydro-pteridine (2-amino-4-hydroxy-6,7-dimethyl-5,6,7,8-tetrahydropterin), of the activated enzyme were 30 and 35 muM respectively.", "contents": "Effects of sulfhydryl agents on the activation of tryptophan-5-monooxygenase from bovine pineal glands. Partially purified tryptophan-5-monooxygenase (L-tryptophan, tetrahydropteridine: oxygen oxidoreductase (5-hydroxylating) EC 1.14.16.4)from bovine pineal gland was activated by preincubation with sulfhydryl agents such as dithiothreitol, L-cysteine, cysteamine, L-cysteine ethylester, N-acetyl-L-cysteine, 2-mercaptoethanol and reduced glutathione, at alkaline pH (optimum pH equals 8.5). Dithiothreitol was the most effective of these, leading to approximately 50-fold activation of the enzyme after preincubation. Fe-2+ or other reducing agents such as borohydride, dithionite and ascorbate facilitated the velocity of the activation in the presence of sulfhydryl agents. In the absence of sulfhydryl agents, no activation was observed even in the presence of Fe-2+ or other reducing agents, suggesting an obligatory role or sulhydryl agents during the activation. The relative velocity and full extent of the activation were dependent on the concentrations of both the sulfhydryl agent and the enzyme in the activation mixture. The kinetic analysis of the activation indicated that the sulfhydryl agent reacts with more than 2 sites in the enzyme; one type of site is reduced by sulfhydryl agents, Fe-2+ or other reducing agents and the other specifically modified by a sulfhydryl agent. The activated enzyme did not require any exogenous Fe-2+ for its catalytic activity, but some roles of iron maybe exist in its catalytic reaction. The optimum pH for catalytic reaction of the activated enzyme was approximately 6.5. The apparent Km for L-tryptophan and pteridine cofactor, tetrahydro-pteridine (2-amino-4-hydroxy-6,7-dimethyl-5,6,7,8-tetrahydropterin), of the activated enzyme were 30 and 35 muM respectively."}
{"id": "PMID:236779", "title": "Purification and properties of rat liver adenine phosphoribosyltransferase.", "content": "The adenine phosphoribosyltransferase (AMP: pyrophosphate phosphoribosyltransferase, EC 2.4.2.7) of rat liver was purified to a specific activity of 1.1 mumol of AMP formed per min per mg. The enzyme activity is associated with an apparently homogenous protein as shown by isoelectrofocusing, acrylamide gel electrophoresis, and N-terminal amino acids analysis (phenylalanine). The molecular weight of the enzyme was estimated to be approx. 20 000 by acrylamide gel electrophoresis in the presence of sodium dodecylsulfate and by sucrose density gradient zone sedimentation. The rat liver enzyme exhibited initial burst synthesis of AMP when 1-pyrophosphorylribose 5-phosphate was added. The 1-pyrophosphorylribose 5-phosphate initial-burst activity copurifies with the adenine phosphoribosyltransferase activity. A PH optimum of 10.0 was demonstrable for the adenine phosphoribosyltransferase. The initial-burst and steady-state phases of AMP synthesis catalyzed by highly purified rat liver adenine phosphoribosyltransferase have been partially characterized by the use of ligands which bind to sulfhydryl groups. Studies utilizing p-chloromercuribenzoate and HgCl2 as inhibitors of AMP sulfhydryl during the initial-burst and steady-state phases have revealed that sulfhydryl groups with different rates of ligand binding are present in the enzyme. The initial-burst phase was thereby delineated from the steady-state phase by use of these mercurial ligands. This delineation was also accomplished by titration with the Mg-2+ chelator, EDTA. The inhibitory effects of mercurials and EDTA were reversed by beta-mercaptoethanol and excess Mg-2+, respectively. Quantitative binding studies with 5,5'-dithiobis(2-nitrobenzoic acid) and p-chloromercuribenzoate yielded values of 3.65 and 3.6 mol of sulfhydryl per mol of enzyme, respectively. 3.3 mol of cysteic acid per mol of performic acid-oxidized enzyme were found by amino acid analysis.", "contents": "Purification and properties of rat liver adenine phosphoribosyltransferase. The adenine phosphoribosyltransferase (AMP: pyrophosphate phosphoribosyltransferase, EC 2.4.2.7) of rat liver was purified to a specific activity of 1.1 mumol of AMP formed per min per mg. The enzyme activity is associated with an apparently homogenous protein as shown by isoelectrofocusing, acrylamide gel electrophoresis, and N-terminal amino acids analysis (phenylalanine). The molecular weight of the enzyme was estimated to be approx. 20 000 by acrylamide gel electrophoresis in the presence of sodium dodecylsulfate and by sucrose density gradient zone sedimentation. The rat liver enzyme exhibited initial burst synthesis of AMP when 1-pyrophosphorylribose 5-phosphate was added. The 1-pyrophosphorylribose 5-phosphate initial-burst activity copurifies with the adenine phosphoribosyltransferase activity. A PH optimum of 10.0 was demonstrable for the adenine phosphoribosyltransferase. The initial-burst and steady-state phases of AMP synthesis catalyzed by highly purified rat liver adenine phosphoribosyltransferase have been partially characterized by the use of ligands which bind to sulfhydryl groups. Studies utilizing p-chloromercuribenzoate and HgCl2 as inhibitors of AMP sulfhydryl during the initial-burst and steady-state phases have revealed that sulfhydryl groups with different rates of ligand binding are present in the enzyme. The initial-burst phase was thereby delineated from the steady-state phase by use of these mercurial ligands. This delineation was also accomplished by titration with the Mg-2+ chelator, EDTA. The inhibitory effects of mercurials and EDTA were reversed by beta-mercaptoethanol and excess Mg-2+, respectively. Quantitative binding studies with 5,5'-dithiobis(2-nitrobenzoic acid) and p-chloromercuribenzoate yielded values of 3.65 and 3.6 mol of sulfhydryl per mol of enzyme, respectively. 3.3 mol of cysteic acid per mol of performic acid-oxidized enzyme were found by amino acid analysis."}
{"id": "PMID:236780", "title": "Cholesteryl ester hydrolytic acitivity of rat liver plasma membrane.", "content": "Cholesteryl ester hydrolyzing activity of rat liver plasma membranes was studied using acetone-dispersed [4-14-C] cholesteryl oleate as substrate. In contrast to whole liver homogenates which displayed ample activity at both acid (4.5) and neutral (6.2-7.4) pH, purified plasma membrane fractions contained little activity at neutral pH as compared to acid pH. Moreover, rate-zonal sucrose density-gradient centrifugation patterns of plasma membrane rich fractions suggested a specific association with plasma membrane only in the case of the acid activity. These findings suggest that in vivo hepatic cell surface membranes contain little or no cholesteryl ester hydrolytic activity at extracellular pH. They support the possibility that plasma lipoprotein cholesteryl esters enter hepatic parenchymal cells prior to hydrolysis.", "contents": "Cholesteryl ester hydrolytic acitivity of rat liver plasma membrane. Cholesteryl ester hydrolyzing activity of rat liver plasma membranes was studied using acetone-dispersed [4-14-C] cholesteryl oleate as substrate. In contrast to whole liver homogenates which displayed ample activity at both acid (4.5) and neutral (6.2-7.4) pH, purified plasma membrane fractions contained little activity at neutral pH as compared to acid pH. Moreover, rate-zonal sucrose density-gradient centrifugation patterns of plasma membrane rich fractions suggested a specific association with plasma membrane only in the case of the acid activity. These findings suggest that in vivo hepatic cell surface membranes contain little or no cholesteryl ester hydrolytic activity at extracellular pH. They support the possibility that plasma lipoprotein cholesteryl esters enter hepatic parenchymal cells prior to hydrolysis."}
{"id": "PMID:236781", "title": "Isoelectric focusing of human serum high density lipoprotein in the presence of radioactive ampholines.", "content": "Preparative isoelectric focusing of a serum high density lipoprotein fraction (rho 1.063-1.125 g/ml) in the presence of radioactive Ampholines showed that there were no significant 14-C-activity peaks in the lipoprotein region of the pH gradient. This suggests that the discrete lipoprotein subspecies obtained by electrofocusing are not artefacts caused by the binding of Ampholines to serum high density lipoprotein.", "contents": "Isoelectric focusing of human serum high density lipoprotein in the presence of radioactive ampholines. Preparative isoelectric focusing of a serum high density lipoprotein fraction (rho 1.063-1.125 g/ml) in the presence of radioactive Ampholines showed that there were no significant 14-C-activity peaks in the lipoprotein region of the pH gradient. This suggests that the discrete lipoprotein subspecies obtained by electrofocusing are not artefacts caused by the binding of Ampholines to serum high density lipoprotein."}
{"id": "PMID:236782", "title": "Effects of cyanide on stearyl-coenzyme A desaturase activities in microsomes from various mammalian tissues.", "content": "The effect of potassium cyanide on the desaturase activity for stearyl-CoA in microsomes of various mammalian tissues has been investigated. Potassium cyanide inhibited the desaturase activities in microsomes from livers of rat, hen, guinea pig and rat lung, but not the activities in microsomes from rabbit liver, pig thyroid and bovine adrenocortex, It is concluded that the so-called \"cyanide-sensitive factor\" does not seem to be common to all the desaturase activities of stearyl-CoA in the microsomes of mammalian tissues.", "contents": "Effects of cyanide on stearyl-coenzyme A desaturase activities in microsomes from various mammalian tissues. The effect of potassium cyanide on the desaturase activity for stearyl-CoA in microsomes of various mammalian tissues has been investigated. Potassium cyanide inhibited the desaturase activities in microsomes from livers of rat, hen, guinea pig and rat lung, but not the activities in microsomes from rabbit liver, pig thyroid and bovine adrenocortex, It is concluded that the so-called \"cyanide-sensitive factor\" does not seem to be common to all the desaturase activities of stearyl-CoA in the microsomes of mammalian tissues."}
{"id": "PMID:236783", "title": "Studies on lipase from Mucor javanicus. I. Purification and properties.", "content": "1. Lipase produced by a mold, Mucor javanicus, was purified about 180-fold from the ethanol precipitate of the culture filtrate. Purification was achieved by acid precipitation followed by gel filtrations on Sephadex G-200 (at low ionic strength) and Sephadex G-75 (at a high ionic strength). The purified enzyme preparation showed unusual behavior on polyacrylamide gel electrophoresis. The molecular weight was estimated to be 21 000. The enzyme had a positional specificity towards the position 1 and 3 of triacylglycerols. 2. Lipase in the crude preparation takes an aggregated form. aggregated form was achieved by raising the ionic strength of the medium. 3. The purified lipase preparation from Mucor javanicus exhibits phospholipase A1 activity, hydrolyzing the carboxyl ester at the 1-position of phosphatidylcholine. This activity seems to be due to the action of the lipase itself and not due to any other specific phospholipases.", "contents": "Studies on lipase from Mucor javanicus. I. Purification and properties. 1. Lipase produced by a mold, Mucor javanicus, was purified about 180-fold from the ethanol precipitate of the culture filtrate. Purification was achieved by acid precipitation followed by gel filtrations on Sephadex G-200 (at low ionic strength) and Sephadex G-75 (at a high ionic strength). The purified enzyme preparation showed unusual behavior on polyacrylamide gel electrophoresis. The molecular weight was estimated to be 21 000. The enzyme had a positional specificity towards the position 1 and 3 of triacylglycerols. 2. Lipase in the crude preparation takes an aggregated form. aggregated form was achieved by raising the ionic strength of the medium. 3. The purified lipase preparation from Mucor javanicus exhibits phospholipase A1 activity, hydrolyzing the carboxyl ester at the 1-position of phosphatidylcholine. This activity seems to be due to the action of the lipase itself and not due to any other specific phospholipases."}
{"id": "PMID:236785", "title": "Induction of tryptophan oxygenase by dexamethasone in isolated hepatocytes. Dependence on composition of medium and pH.", "content": "Hepatocytes were isolated from perfused rat livers. 4 x 10-6 cells/ml were incubated at at 37 degrees C in different media in the absence and presence of a steroid hormone, dexamethasone phosphate (2 x 10-5 M). 1. Hormonal enzyme induction occurred in cells suspended in a simple salt medium, devoid of amino acids and macromolecules. This induction was completely blocked by addition of either actinomycin D (2 mu-g/ml) or cycloheximide (50 mu-g/ml). 2. Incubation of cells in media containing defatted albumin did not enhance hormonal enzyme induction, although disintegration of cells during incubation was reduced. Addition of a crude albumin fraction reduced tryptophan oxygenase induction and dextran completely blocked enzyme induction by dexamethasone. 3. An increase of dexamethasone concentration in the presence of albumin to 9 x 10-5 M was unable to raise enzyme induction further, and a still higher concentration of hormone, 3 x 10-4 M, resulted in reduced enzyme induction. 4. The hormonal induction of tryptophan oxygenase was most pronounced when the pH of the medium was between 7.0 and 7.6, with an optium at 7.3. No induction was found when the pH of the medium was either 6.6 or 7.8. The basal tryptophan oxygenase activity was much less influenced by similar pH variations. It is concluded that hepatocytes in suspension are able to carry out hormone-stimulated enzyme synthesis and that factors influencing this process may be studied under controlled conditions in such systems.", "contents": "Induction of tryptophan oxygenase by dexamethasone in isolated hepatocytes. Dependence on composition of medium and pH. Hepatocytes were isolated from perfused rat livers. 4 x 10-6 cells/ml were incubated at at 37 degrees C in different media in the absence and presence of a steroid hormone, dexamethasone phosphate (2 x 10-5 M). 1. Hormonal enzyme induction occurred in cells suspended in a simple salt medium, devoid of amino acids and macromolecules. This induction was completely blocked by addition of either actinomycin D (2 mu-g/ml) or cycloheximide (50 mu-g/ml). 2. Incubation of cells in media containing defatted albumin did not enhance hormonal enzyme induction, although disintegration of cells during incubation was reduced. Addition of a crude albumin fraction reduced tryptophan oxygenase induction and dextran completely blocked enzyme induction by dexamethasone. 3. An increase of dexamethasone concentration in the presence of albumin to 9 x 10-5 M was unable to raise enzyme induction further, and a still higher concentration of hormone, 3 x 10-4 M, resulted in reduced enzyme induction. 4. The hormonal induction of tryptophan oxygenase was most pronounced when the pH of the medium was between 7.0 and 7.6, with an optium at 7.3. No induction was found when the pH of the medium was either 6.6 or 7.8. The basal tryptophan oxygenase activity was much less influenced by similar pH variations. It is concluded that hepatocytes in suspension are able to carry out hormone-stimulated enzyme synthesis and that factors influencing this process may be studied under controlled conditions in such systems."}
{"id": "PMID:236786", "title": "Analysis of polypeptide disposition in human erythrocyte membranes employing membrane inversion.", "content": "High resolution segregation of erythrocyte membrane polypeptides achieved by isoelectric focusing in 8 M urea was employed in conjunction with surface-restricted radioiodination to analyze the disposition of polypeptides within the human erythrocyte membrane. Several membrane polypeptides showed significant uptake of radioiodine, with the principal labeled component migrating between pH values of 3.0 and 3.5. Two approaches were taken in examining membrane polypeptide disposition on both faces of the erythrocyte membrane. Saturation labeling of the outer face of the membrane with one iodine isotope followed by cell lysis and reiodination with a second iodine isotope did not prove feasible and another procedure based on surface iodination with 125-I, formation of sealed inside-out vesicles and re-iodination with 131-I was adopted. Studies of sialic acid release from the membrane surface and trypsin cleavage of radioiodinated peptides indicated that selectively labeled, sealed inside-out vesicles had been formed. The ratio of 125-I to 131-I in membrane polypeptides separated by isoelectric focusing confirmed the existence of externally disposed, internally disposed and spanning proteins.", "contents": "Analysis of polypeptide disposition in human erythrocyte membranes employing membrane inversion. High resolution segregation of erythrocyte membrane polypeptides achieved by isoelectric focusing in 8 M urea was employed in conjunction with surface-restricted radioiodination to analyze the disposition of polypeptides within the human erythrocyte membrane. Several membrane polypeptides showed significant uptake of radioiodine, with the principal labeled component migrating between pH values of 3.0 and 3.5. Two approaches were taken in examining membrane polypeptide disposition on both faces of the erythrocyte membrane. Saturation labeling of the outer face of the membrane with one iodine isotope followed by cell lysis and reiodination with a second iodine isotope did not prove feasible and another procedure based on surface iodination with 125-I, formation of sealed inside-out vesicles and re-iodination with 131-I was adopted. Studies of sialic acid release from the membrane surface and trypsin cleavage of radioiodinated peptides indicated that selectively labeled, sealed inside-out vesicles had been formed. The ratio of 125-I to 131-I in membrane polypeptides separated by isoelectric focusing confirmed the existence of externally disposed, internally disposed and spanning proteins."}
{"id": "PMID:236787", "title": "The purification and characterization of plasma membranes and the subcellular distribution of adenylate cyclase in mouse parotid gland.", "content": "1. Plasma membranes have been purified 17-fold from mouse parotid gland homogenates prepared in hypertonic sucrose media using differential centrifugation. The method is fast and simple. The membranes were characterised by electron microscopy, enzyme composition and chemical composition. Further purification was achieved by isopycnic centrifugation in discontinuous sucrose gradients. 2. The purified membranes contain an adenylate cyclase activity which is stimulated by isoproterenol and fluoride. Only 50% of the total adenylate cyclase activity sedimented in the plasma membrane fraction. The rest of the activity resided in the crude nuclear and mitochondrial pellets. However, this adenylate cyclase activity was not associated with these organelles but with membrane fragments in the pellets. Purified nuclei did not contain adenylate cyclase activity. 3. Adenylate cyclase activity was also localised by electron microscopic cytochemistry. Besides being found at the plasma membrane, large amounts of adenylate cyclase were found in a small proportion of the vesicles within the acinar cells, which appeared to be secondary lysosomes. 4. Adenylate cyclase activities, under standard assay conditions, are proportional to the time of incubation and the concentration of enzyme. The enzyme requires both Mg-2+ and CA-2+ for activity. Isoproterenol increased activity 2-fold and this increase is abolished by beta-adrenergic blocking agents.", "contents": "The purification and characterization of plasma membranes and the subcellular distribution of adenylate cyclase in mouse parotid gland. 1. Plasma membranes have been purified 17-fold from mouse parotid gland homogenates prepared in hypertonic sucrose media using differential centrifugation. The method is fast and simple. The membranes were characterised by electron microscopy, enzyme composition and chemical composition. Further purification was achieved by isopycnic centrifugation in discontinuous sucrose gradients. 2. The purified membranes contain an adenylate cyclase activity which is stimulated by isoproterenol and fluoride. Only 50% of the total adenylate cyclase activity sedimented in the plasma membrane fraction. The rest of the activity resided in the crude nuclear and mitochondrial pellets. However, this adenylate cyclase activity was not associated with these organelles but with membrane fragments in the pellets. Purified nuclei did not contain adenylate cyclase activity. 3. Adenylate cyclase activity was also localised by electron microscopic cytochemistry. Besides being found at the plasma membrane, large amounts of adenylate cyclase were found in a small proportion of the vesicles within the acinar cells, which appeared to be secondary lysosomes. 4. Adenylate cyclase activities, under standard assay conditions, are proportional to the time of incubation and the concentration of enzyme. The enzyme requires both Mg-2+ and CA-2+ for activity. Isoproterenol increased activity 2-fold and this increase is abolished by beta-adrenergic blocking agents."}
{"id": "PMID:236788", "title": "Distribution of NAD(P)H-dependent cytochrome P-450 mixed function oxidase system in the brush border membrane of rabbit kidney cortex.", "content": "Optical and magnetic studies were made on subfractions of rabbit kidney cortex. Cytochrome P-450 and cytochrome b5-dependent mixed function oxidase systems were localized mainly in the brush border membranes and microsomes. Cytochrome P-450-dependent mixed function oxidases in the membranes comprised both an NADPH-dependent system and an NADH-dependent system.", "contents": "Distribution of NAD(P)H-dependent cytochrome P-450 mixed function oxidase system in the brush border membrane of rabbit kidney cortex. Optical and magnetic studies were made on subfractions of rabbit kidney cortex. Cytochrome P-450 and cytochrome b5-dependent mixed function oxidase systems were localized mainly in the brush border membranes and microsomes. Cytochrome P-450-dependent mixed function oxidases in the membranes comprised both an NADPH-dependent system and an NADH-dependent system."}
{"id": "PMID:236789", "title": "On the effects of propionate and other short-chain fatty acids on sodium transport by the toad bladder.", "content": "1. Propionate and other unbranched short-chain fatty acids, butyrate, pentanoate, hexanoate and octanoate were found to both stimulate and inhibit active sodium transport by the toad bladder, as measured by the short-circuit current (s.c.c.). 2. Stimulation alone followed addition of low concentrations of fatty acids (0.1-1.0 mM) to either the serosal or mucosal bathing medium; stimulation was also seen after an initial period of inhibition in response to higher concentrations (approx. 5 mM) of some compounds. 3. Inhibition alone followed addition of high concentrations (5-20 mM) of these compounds. The duration and magnitude of the inhibition varied with increasing concentration and chain length of the fatty acid, and was greater following mucosal addition than serosal addition. 4. The inhibitory effect of mucosal propionate increased with decreasing pH of the mucosal bathing medium. 5. Inhibition by the fatty acids was completely reversed upon removing the compound from the bathing medium, and stimulation characteristically followed. 6. In studies designed to evaluate the role of metabolism of the fatty acids in their mucosal inhibitory effects it was found that 14-c-labelled propionate, when added to the mucosal surface of the bladder, was converted to 14-CO2, and mucosal succinate and alpha-oxoglutaric acid at 20 mM inhibited the s.c.c. slightly. However, malonate did not interfere with inhibition by mucosal propionate and two non-metabolizable acids, dimethylpropionate and benzoate, induced inhibition (and no stimulation) of the s.c.c. 7. In the presence of an inhibitory concentration of fatty acid, the ability of the bladder to respond to added pyruvate was reduced in proportion to the reduction in the level of the s.c.c., whereas the natriferic response to vasopressin was largely intact. 8. We conclude that stimulation of sodium transport by propionate and other short-chain fatty acids is due to metabolism of the compounds and provision of energy to the sodium transport mechanism. The basis of the inhibition appears complex. It may in part depend on metabolism of the fatty acids and/or uncoupling of oxidative phosphorylation, with resultant reduction in net ATP production for the sodium transport mechanism. However, the inhibition may also be caused in part by a direct effect on the mucosal entry of sodium into the transporting epithelial cells.", "contents": "On the effects of propionate and other short-chain fatty acids on sodium transport by the toad bladder. 1. Propionate and other unbranched short-chain fatty acids, butyrate, pentanoate, hexanoate and octanoate were found to both stimulate and inhibit active sodium transport by the toad bladder, as measured by the short-circuit current (s.c.c.). 2. Stimulation alone followed addition of low concentrations of fatty acids (0.1-1.0 mM) to either the serosal or mucosal bathing medium; stimulation was also seen after an initial period of inhibition in response to higher concentrations (approx. 5 mM) of some compounds. 3. Inhibition alone followed addition of high concentrations (5-20 mM) of these compounds. The duration and magnitude of the inhibition varied with increasing concentration and chain length of the fatty acid, and was greater following mucosal addition than serosal addition. 4. The inhibitory effect of mucosal propionate increased with decreasing pH of the mucosal bathing medium. 5. Inhibition by the fatty acids was completely reversed upon removing the compound from the bathing medium, and stimulation characteristically followed. 6. In studies designed to evaluate the role of metabolism of the fatty acids in their mucosal inhibitory effects it was found that 14-c-labelled propionate, when added to the mucosal surface of the bladder, was converted to 14-CO2, and mucosal succinate and alpha-oxoglutaric acid at 20 mM inhibited the s.c.c. slightly. However, malonate did not interfere with inhibition by mucosal propionate and two non-metabolizable acids, dimethylpropionate and benzoate, induced inhibition (and no stimulation) of the s.c.c. 7. In the presence of an inhibitory concentration of fatty acid, the ability of the bladder to respond to added pyruvate was reduced in proportion to the reduction in the level of the s.c.c., whereas the natriferic response to vasopressin was largely intact. 8. We conclude that stimulation of sodium transport by propionate and other short-chain fatty acids is due to metabolism of the compounds and provision of energy to the sodium transport mechanism. The basis of the inhibition appears complex. It may in part depend on metabolism of the fatty acids and/or uncoupling of oxidative phosphorylation, with resultant reduction in net ATP production for the sodium transport mechanism. However, the inhibition may also be caused in part by a direct effect on the mucosal entry of sodium into the transporting epithelial cells."}
{"id": "PMID:236790", "title": "Osmotic behaviour of Acholeplasma laidlawii B cells with membrane lipids in liquid-crystalline and gel state.", "content": "The osmotic behaviour of Acholeplasma laidlawii B cells was investigated with combined spectrophotometric and enzymatic measurements. The conclusion could be drawn that this osmotic behaviour depends largely on the physical state of the membrane lipids. When part of the membrane lipids is in the liquid-crystalline phase the cell is able to swell and behaves as a good osmometer. However, when the membrane lipid is in the gel phase, the cell is unable to swell and the change in absorbance of the cell suspension is then completely due to lysis.", "contents": "Osmotic behaviour of Acholeplasma laidlawii B cells with membrane lipids in liquid-crystalline and gel state. The osmotic behaviour of Acholeplasma laidlawii B cells was investigated with combined spectrophotometric and enzymatic measurements. The conclusion could be drawn that this osmotic behaviour depends largely on the physical state of the membrane lipids. When part of the membrane lipids is in the liquid-crystalline phase the cell is able to swell and behaves as a good osmometer. However, when the membrane lipid is in the gel phase, the cell is unable to swell and the change in absorbance of the cell suspension is then completely due to lysis."}
{"id": "PMID:236796", "title": "Effect of morphine on adrenergic transmission in the mouse vas deferens. Assessment of agonist and antogonist potencies of narcotic analgesics.", "content": "1. Morphine inhibits the electrically evoked (0.1-0.15 Hz, 1 ms) contractions of the longitudinal muscle of the mouse vas deferens but not of the rabbit, guinea-pig, rat, cat, hamster or gerbil. This effect is stereospecific and is antagonized by naloxone or naltrexone. 2. Normorphine is equiactive with morphine but its effects are more rapid in onset and decline. 3. In the mouse vas deferens, the resting outflow of tritium-labelled catecholamines is unaffected by morphine. The electrically evoked outflow is depressed by morphine or normorphine in a dose-dependent manner. The ID50 for inhibition of contraction and for depression of outflow is 0.5 muM. 4. The relative agonist potencies of compounds without antagonist component (codeine, pethidine, morphine, normorphine, heroin, levorphanol, Ba-20227, etorphine) show good correlation with the relative agonist potencies determined in the guinea-pig ileum and for analgesia in man. 5. For compounds with dual agonist and antagonist properties, the dose-response curves for agonist activity are shallow. When the lowest concentrations giving a depression of the contraction of the mouse vas deferens are used, a good correlation is obtained with the guinea-pig ileum. 6. The relative antagonist potencies of naloxone, nalorphine, levallorphan, and cyclazocine agree well with those obtained in the guinea-pig ileum; these, in turn, correlate well with the values obtained in the morphine-dependent monkey. 7. The fact that the agonist effects of drugs with dual agonist and antagonist action show little or no dependence on concentration, makes the mouse vas deferens particularly suitable for the assay of assay of antagonist activity. 8. As an assay preparation, the mouse vas deferens is less robust and consistent in its responses than the guinea-pig ileum.", "contents": "Effect of morphine on adrenergic transmission in the mouse vas deferens. Assessment of agonist and antogonist potencies of narcotic analgesics. 1. Morphine inhibits the electrically evoked (0.1-0.15 Hz, 1 ms) contractions of the longitudinal muscle of the mouse vas deferens but not of the rabbit, guinea-pig, rat, cat, hamster or gerbil. This effect is stereospecific and is antagonized by naloxone or naltrexone. 2. Normorphine is equiactive with morphine but its effects are more rapid in onset and decline. 3. In the mouse vas deferens, the resting outflow of tritium-labelled catecholamines is unaffected by morphine. The electrically evoked outflow is depressed by morphine or normorphine in a dose-dependent manner. The ID50 for inhibition of contraction and for depression of outflow is 0.5 muM. 4. The relative agonist potencies of compounds without antagonist component (codeine, pethidine, morphine, normorphine, heroin, levorphanol, Ba-20227, etorphine) show good correlation with the relative agonist potencies determined in the guinea-pig ileum and for analgesia in man. 5. For compounds with dual agonist and antagonist properties, the dose-response curves for agonist activity are shallow. When the lowest concentrations giving a depression of the contraction of the mouse vas deferens are used, a good correlation is obtained with the guinea-pig ileum. 6. The relative antagonist potencies of naloxone, nalorphine, levallorphan, and cyclazocine agree well with those obtained in the guinea-pig ileum; these, in turn, correlate well with the values obtained in the morphine-dependent monkey. 7. The fact that the agonist effects of drugs with dual agonist and antagonist action show little or no dependence on concentration, makes the mouse vas deferens particularly suitable for the assay of assay of antagonist activity. 8. As an assay preparation, the mouse vas deferens is less robust and consistent in its responses than the guinea-pig ileum."}
{"id": "PMID:236797", "title": "Action of beta-adrenoceptor antagonists on the response to isoprenaline in the oestrogen dominated rabbit uterus.", "content": "1. Log dose-response curves to isoprenaline from spontaneously contracting muscle strips from rabbit uterus have been obtained. The effects of the alpha-adrenoceptor antagonists phentolamine and phenoxybenzamine, the beta- adrenoceptor antagonists propranolol and practolol, and (+)-propranolol on the log dose-response curves were studied. 2. Phentolamine 5.3 times 10- minus 7 M had a stimulating effect on the muscle strips, moving the log dose-response curve of isoprenaline to the right. Phenoxybenzamine 2.9 times 10- minus 5 M had no effect on the curves. 3. Propranolol 3.4 times 10- minus 6 M had no effect on the curves from circular muscle strips, with either phentolamine 5.4 times 10- minus 7 M or with phenoxybenzamine 2.9 times 10- minus 5 M as alpha-blocker. The curves from the longitudinal muscle strips were shifted somewhat to the right, the same shift, however, being obtained with (+)-propranolol 3.4 times 10- minus 6 M. 4. Practolol 3.8 times 10- minus 6, 3.8 times 10- minus 5 and 3.8 times 10- minus 4 M was without effect on the curves, either in the circular or in the longitudinal strips. 5. It is concluded that neither propranolol at 3.4 times 10- minus 6 M nor practolol act as beta-adrenoceptor antagonists in oestrogen dominated rabbit uterus. In all other tissues investigated, propranolol or practolol block the effect of isoprenaline. Whether the effect of isoprenaline in this tissue may be termed a beta-effect, is then a question of definition. In addition there is no evidence for any extraneuronal uptake mechanisms for isoprenaline. 6. Variations in sensitivity to beta-stimulation with the time of the year were observed, the sensitivity being greatest in the winter and lowest in the summer.", "contents": "Action of beta-adrenoceptor antagonists on the response to isoprenaline in the oestrogen dominated rabbit uterus. 1. Log dose-response curves to isoprenaline from spontaneously contracting muscle strips from rabbit uterus have been obtained. The effects of the alpha-adrenoceptor antagonists phentolamine and phenoxybenzamine, the beta- adrenoceptor antagonists propranolol and practolol, and (+)-propranolol on the log dose-response curves were studied. 2. Phentolamine 5.3 times 10- minus 7 M had a stimulating effect on the muscle strips, moving the log dose-response curve of isoprenaline to the right. Phenoxybenzamine 2.9 times 10- minus 5 M had no effect on the curves. 3. Propranolol 3.4 times 10- minus 6 M had no effect on the curves from circular muscle strips, with either phentolamine 5.4 times 10- minus 7 M or with phenoxybenzamine 2.9 times 10- minus 5 M as alpha-blocker. The curves from the longitudinal muscle strips were shifted somewhat to the right, the same shift, however, being obtained with (+)-propranolol 3.4 times 10- minus 6 M. 4. Practolol 3.8 times 10- minus 6, 3.8 times 10- minus 5 and 3.8 times 10- minus 4 M was without effect on the curves, either in the circular or in the longitudinal strips. 5. It is concluded that neither propranolol at 3.4 times 10- minus 6 M nor practolol act as beta-adrenoceptor antagonists in oestrogen dominated rabbit uterus. In all other tissues investigated, propranolol or practolol block the effect of isoprenaline. Whether the effect of isoprenaline in this tissue may be termed a beta-effect, is then a question of definition. In addition there is no evidence for any extraneuronal uptake mechanisms for isoprenaline. 6. Variations in sensitivity to beta-stimulation with the time of the year were observed, the sensitivity being greatest in the winter and lowest in the summer."}
{"id": "PMID:236801", "title": "Determination of the Optimum temperature for regional renal hypothermia during temporary renal ischaemia.", "content": "To determine the optimum temperature at which the in situ kidney should be maintained while it is ischaemic, 47 mongrel dogs were studied. 35 of these underwent 90 minutes of left renal ischaemia with the kidney temperature maintained at 37 degree, 30 degree, 22 degree, 15 degree and 0 degree C respectively. The effect on renal function was determined by measurements of G.F.R. before and at regular 15-minute intervals after the inschaemic period. Computer statistical analysis exposed the optimum temperature to be 15 degree C. Renal artery blood flow, renal histology, 15-Cr labelled platelets and renal arteriography were used to determine the mechanism of ischaemic injury. Quantitation of renal cell injury confirmed that no additional protection to ischaemia could be gained by colling below 15 degree C. 15 degree C is recommended as the optimum temperature for use in clinical renal hypothermia.", "contents": "Determination of the Optimum temperature for regional renal hypothermia during temporary renal ischaemia. To determine the optimum temperature at which the in situ kidney should be maintained while it is ischaemic, 47 mongrel dogs were studied. 35 of these underwent 90 minutes of left renal ischaemia with the kidney temperature maintained at 37 degree, 30 degree, 22 degree, 15 degree and 0 degree C respectively. The effect on renal function was determined by measurements of G.F.R. before and at regular 15-minute intervals after the inschaemic period. Computer statistical analysis exposed the optimum temperature to be 15 degree C. Renal artery blood flow, renal histology, 15-Cr labelled platelets and renal arteriography were used to determine the mechanism of ischaemic injury. Quantitation of renal cell injury confirmed that no additional protection to ischaemia could be gained by colling below 15 degree C. 15 degree C is recommended as the optimum temperature for use in clinical renal hypothermia."}
{"id": "PMID:236802", "title": "Immunological effects of orchidectomy.", "content": "Orchidectomy caused a non-specific increase of immunological reactivity in mice evidenced by accelerated rejection of skin allografts, increased response to oxazolone and sheep erythrocytes. These changes were associated with an increase of thymic size. The response to pneumococcal polysaccharide, which depends upon B-cells, was not increased. Orchidectomised mice showed protection against induced methylcholanthrene sarcomas and transplantable tumours; tumours which are not obviously hormone dependent.", "contents": "Immunological effects of orchidectomy. Orchidectomy caused a non-specific increase of immunological reactivity in mice evidenced by accelerated rejection of skin allografts, increased response to oxazolone and sheep erythrocytes. These changes were associated with an increase of thymic size. The response to pneumococcal polysaccharide, which depends upon B-cells, was not increased. Orchidectomised mice showed protection against induced methylcholanthrene sarcomas and transplantable tumours; tumours which are not obviously hormone dependent."}
{"id": "PMID:236804", "title": "Relief of duodenal ulcer sysmptons by oral metiamide.", "content": "Thirty patients with symptoms of duodenal ulceration were treated for five to eight weeks in a double-blind trial with either metiamide 1 g daily by mouth or a placebo. In the 15 patients receiving metiamide there were significant reductions in nocturnal pain and antacid consumption. Daytime pain was diminished. The results suggest that histamine H2-receptor antagonists are likely to be useful in the medical management of the symptoms of duodenal ulceration.", "contents": "Relief of duodenal ulcer sysmptons by oral metiamide. Thirty patients with symptoms of duodenal ulceration were treated for five to eight weeks in a double-blind trial with either metiamide 1 g daily by mouth or a placebo. In the 15 patients receiving metiamide there were significant reductions in nocturnal pain and antacid consumption. Daytime pain was diminished. The results suggest that histamine H2-receptor antagonists are likely to be useful in the medical management of the symptoms of duodenal ulceration."}
{"id": "PMID:236805", "title": "Long-term study of indomethacin and alclofenac in treatment of rheumatoid arthritis.", "content": "Indomethacin and alclofenac were compared for 13 months under double-blind conditions in 109 patients with active, classical, or definite rheumatoid arthritis at a relatively early stage of the disease. Both indomethacin and alclofenac were clearly effective: most patients either improved or remained as well controlled as on entry. Alclofenac proved the more effective drug, however, producing a significantly greater reduction in morning stiffness, articular index, and erythrocyte sedimentation rate, and only in the alclofenac-treated group did functional capacity improve and latex-agglutination titres diminish. Comprehensive laborabory tests showed no significant deviation from normal which could have been attributed to either drug.", "contents": "Long-term study of indomethacin and alclofenac in treatment of rheumatoid arthritis. Indomethacin and alclofenac were compared for 13 months under double-blind conditions in 109 patients with active, classical, or definite rheumatoid arthritis at a relatively early stage of the disease. Both indomethacin and alclofenac were clearly effective: most patients either improved or remained as well controlled as on entry. Alclofenac proved the more effective drug, however, producing a significantly greater reduction in morning stiffness, articular index, and erythrocyte sedimentation rate, and only in the alclofenac-treated group did functional capacity improve and latex-agglutination titres diminish. Comprehensive laborabory tests showed no significant deviation from normal which could have been attributed to either drug."}
{"id": "PMID:236806", "title": "Comparison of intravenous AH 5158 (ibidomide) and propranolol in asthma.", "content": "The cardiac and bronchial effects of AH 5158 and propranolol were compared in a double-blind, placebocontrolled intravenous study on 10 asthmatics. AH 5158, like propranolol, is a non-cardioselective beta-adrenoceptor-blocking drug, but unlike propranolol it also has an alpha-adrenoceptor-blocking action. Both drugs produced equivalent cardiac(beta1) blockade, but propranolol produced bronchoconstriction, whereas AH 5158 did not. Hence the alpha-blocking action of AH 5158 seems to prevent the bronchoconstrictor effects of propranolol in these patients.", "contents": "Comparison of intravenous AH 5158 (ibidomide) and propranolol in asthma. The cardiac and bronchial effects of AH 5158 and propranolol were compared in a double-blind, placebocontrolled intravenous study on 10 asthmatics. AH 5158, like propranolol, is a non-cardioselective beta-adrenoceptor-blocking drug, but unlike propranolol it also has an alpha-adrenoceptor-blocking action. Both drugs produced equivalent cardiac(beta1) blockade, but propranolol produced bronchoconstriction, whereas AH 5158 did not. Hence the alpha-blocking action of AH 5158 seems to prevent the bronchoconstrictor effects of propranolol in these patients."}
{"id": "PMID:236809", "title": "Response of lymphocyte guanyl cyclase to propranolol, noradrenaline, thymoxamine, and acetylcholine in extrinsic bronchial asthma.", "content": "The lymphocyte guanyl cyclase response to alpha-agonists was studied in 10 normal people and 12 patients with bronchial asthma. In the normal subjects alpha-adrenergic stimulation with noradrenaline plus propranolol and cholinergic stimulation with acetylcholine evoked significant increases in cyclic guanosine monophosphate formation. In addition the alpha-receptor blocking drug thymoxamine produced a significant stimulation of this enzyme system, and the effects of thymoxamine and acetylcholine were additive. This suggests that receptors for cholinergic and alpha-adrenergic agents are independent. In contrast, lymphocyte guanyl cyclase activity did not show a significant response to these agents in patients with acute asthma. In asthmatic patients in remission the responses were partially restored. The significance of these results for control of bronchomotor tone and the relation of guanyl cyclase activity to cyclic adenosine monophosphate in normal subjects and patients with asthma is discussed.", "contents": "Response of lymphocyte guanyl cyclase to propranolol, noradrenaline, thymoxamine, and acetylcholine in extrinsic bronchial asthma. The lymphocyte guanyl cyclase response to alpha-agonists was studied in 10 normal people and 12 patients with bronchial asthma. In the normal subjects alpha-adrenergic stimulation with noradrenaline plus propranolol and cholinergic stimulation with acetylcholine evoked significant increases in cyclic guanosine monophosphate formation. In addition the alpha-receptor blocking drug thymoxamine produced a significant stimulation of this enzyme system, and the effects of thymoxamine and acetylcholine were additive. This suggests that receptors for cholinergic and alpha-adrenergic agents are independent. In contrast, lymphocyte guanyl cyclase activity did not show a significant response to these agents in patients with acute asthma. In asthmatic patients in remission the responses were partially restored. The significance of these results for control of bronchomotor tone and the relation of guanyl cyclase activity to cyclic adenosine monophosphate in normal subjects and patients with asthma is discussed."}
{"id": "PMID:236810", "title": "Controlled study of atenolol in treatment of hypertension.", "content": "The antihypertensive effect of atenolol, a new beta-1-receptor blocking agent, was studied in a double-blind trial in which 45 patients with essential hypertension were randomly assigned to placebo or atenolol treatment. Atenolol caused a statistically significant and clinically relevant reduction of blood pressure. The optimum daily dose for moderately severe hypertension was considered to be 200 mg. Several irrelevant side effects were collected by the use of a check list, but there was no difference in the number of complaints during placebo and active treatment. Atenolol has a useful antihypertensive effect and, at least theoretically, has advantages over other beta-adrenergic blocking agents.", "contents": "Controlled study of atenolol in treatment of hypertension. The antihypertensive effect of atenolol, a new beta-1-receptor blocking agent, was studied in a double-blind trial in which 45 patients with essential hypertension were randomly assigned to placebo or atenolol treatment. Atenolol caused a statistically significant and clinically relevant reduction of blood pressure. The optimum daily dose for moderately severe hypertension was considered to be 200 mg. Several irrelevant side effects were collected by the use of a check list, but there was no difference in the number of complaints during placebo and active treatment. Atenolol has a useful antihypertensive effect and, at least theoretically, has advantages over other beta-adrenergic blocking agents."}
{"id": "PMID:236814", "title": "Neurons from fetal rat brain in a new cell culture system: a multidisciplinary analysis.", "content": "A new culture system for cells from the mammalian brain was developed by a modification of a previously established technique. This modification involved the use of fluorodeoxyuridine and adult horse serum. The cultures contained large, easily visualized neurons both isolated from other neurons and in networks of varying complexity. These cells were large enough to permit reliable intracellular electrophysiologic recording and were often sufficiently dispersed to allow examination of membrane responses to iontophoretically applied neurotransmitter candidates. Many responses characteristic of central neurons in situ were seen, including evoked and spontaneous action potentials, complex patterns of inhibitory and excitatory post-synaptic potentials, and neurotransmitter-induced membrane responses. These preparations were examined by phase contrast microscopy, by light microscopy after silver impregnation and by Nomarski interference optics. Total choline acetyltransferase (CAT) activity was little changed and specific activity was increased in the new culture system as compared with the earilier system. Conditions which gave the highest specific activity of CAT also provided the best cultures from the standpoint of electrophysiologic and morphologic analysis. This new approach will allow, in culture, detailed multidisciplinary analyses of individual neurons and small networks of neurons from the mammalian brain.", "contents": "Neurons from fetal rat brain in a new cell culture system: a multidisciplinary analysis. A new culture system for cells from the mammalian brain was developed by a modification of a previously established technique. This modification involved the use of fluorodeoxyuridine and adult horse serum. The cultures contained large, easily visualized neurons both isolated from other neurons and in networks of varying complexity. These cells were large enough to permit reliable intracellular electrophysiologic recording and were often sufficiently dispersed to allow examination of membrane responses to iontophoretically applied neurotransmitter candidates. Many responses characteristic of central neurons in situ were seen, including evoked and spontaneous action potentials, complex patterns of inhibitory and excitatory post-synaptic potentials, and neurotransmitter-induced membrane responses. These preparations were examined by phase contrast microscopy, by light microscopy after silver impregnation and by Nomarski interference optics. Total choline acetyltransferase (CAT) activity was little changed and specific activity was increased in the new culture system as compared with the earilier system. Conditions which gave the highest specific activity of CAT also provided the best cultures from the standpoint of electrophysiologic and morphologic analysis. This new approach will allow, in culture, detailed multidisciplinary analyses of individual neurons and small networks of neurons from the mammalian brain."}
{"id": "PMID:236817", "title": "The inotropic and chronotropic responses of the guinea pig and dog myocardium to isoprenaline and salbutamol.", "content": "The relative effects of isoprenaline and salbutamol on the inotropic and chronotropic responses of the denervated myocardium of the chloralose anesthetized dog and of the isolated guinea pig atrium, and the inotropic response of the isolated dog papillary muscle were studied. Both the in vivo dog heart and the in vitro guinea pig atrium displayed a similar relative response pattern to isoprenaline and salbutamol with regard to their inotropic and chronotropic responses. However, a comparison of the relative inotropic responses of the dog heart in vivo and in vitro showed that in vitro, salbutamol has a much lower affinity and efficacy for the adrenergic receptors than isoprenaline.", "contents": "The inotropic and chronotropic responses of the guinea pig and dog myocardium to isoprenaline and salbutamol. The relative effects of isoprenaline and salbutamol on the inotropic and chronotropic responses of the denervated myocardium of the chloralose anesthetized dog and of the isolated guinea pig atrium, and the inotropic response of the isolated dog papillary muscle were studied. Both the in vivo dog heart and the in vitro guinea pig atrium displayed a similar relative response pattern to isoprenaline and salbutamol with regard to their inotropic and chronotropic responses. However, a comparison of the relative inotropic responses of the dog heart in vivo and in vitro showed that in vitro, salbutamol has a much lower affinity and efficacy for the adrenergic receptors than isoprenaline."}
{"id": "PMID:236818", "title": "Magnesium binding in the digesta of the chicken.", "content": "Two experiments involving laying hens and mature roosters were carried out to determine the effect of pH on the ultrafilterable fraction of Mg((Mg)u) present in the digesta along the gastrointestinal tract. Concurrently, the approximate molecular weight of the (Mg)u was determined. The average pH's for laying hens were: crop 4.88, proventriculus 5.27, ventriculus 4.77, duodenum 5.57, jejunum 6.15, ileum 7.82, and colon 6.65. Similar pH values were obtained for mature roosters. The (Mg)u fraction decreased significantly in the ileum where the pH was greater than 7.00. However, treating the ileal digesta with an acid pH buffer released about 70% of the nonfilterable Mg. The molecular weight of the (Mg)u was found to be less than 700, suggesting that the Mg was present in digesta as an inorganic salt or as an organic complex of low molecular weight.", "contents": "Magnesium binding in the digesta of the chicken. Two experiments involving laying hens and mature roosters were carried out to determine the effect of pH on the ultrafilterable fraction of Mg((Mg)u) present in the digesta along the gastrointestinal tract. Concurrently, the approximate molecular weight of the (Mg)u was determined. The average pH's for laying hens were: crop 4.88, proventriculus 5.27, ventriculus 4.77, duodenum 5.57, jejunum 6.15, ileum 7.82, and colon 6.65. Similar pH values were obtained for mature roosters. The (Mg)u fraction decreased significantly in the ileum where the pH was greater than 7.00. However, treating the ileal digesta with an acid pH buffer released about 70% of the nonfilterable Mg. The molecular weight of the (Mg)u was found to be less than 700, suggesting that the Mg was present in digesta as an inorganic salt or as an organic complex of low molecular weight."}
{"id": "PMID:236820", "title": "Long-term therapy of chronic bacterial prostatitis with trimethoprim-sulfamethoxazole.", "content": "Trimethoprim (TMP) meets all of the theoretical requirements of diffusion into, and actual concentration in, human prostatic fluid. When TMP is combined with the sulfonamide sulfamethoxazole (SMX), potentiation of antibacterial activity is achieved and the development of resistant bacterial strains is less likely to occur. In our initial use of TMP-SMX in the treatment of 13 men with chronic bacterial prostatitis due to gram-negative organisms, patients were given two tablets of TMP-SMX twice daily for only 14 days. The results were that two patients (15%) were cured, nine patients (70%) were improved (sterile prostatic fluid during therapy) but eventually relapsed, and two patients (15%) were unchanged by therapy. In our present study 19 patients (31.6%) were totally cured and 9 of 23 (39.1%) gram-negative organisms were permanently cleared from prostatic fluid; 8 of the 9 patients (42.1%) were improved but eventually relapsed with the same organism; 5 of the 19 patients (26.3%) were considered unchanged by therapy.", "contents": "Long-term therapy of chronic bacterial prostatitis with trimethoprim-sulfamethoxazole. Trimethoprim (TMP) meets all of the theoretical requirements of diffusion into, and actual concentration in, human prostatic fluid. When TMP is combined with the sulfonamide sulfamethoxazole (SMX), potentiation of antibacterial activity is achieved and the development of resistant bacterial strains is less likely to occur. In our initial use of TMP-SMX in the treatment of 13 men with chronic bacterial prostatitis due to gram-negative organisms, patients were given two tablets of TMP-SMX twice daily for only 14 days. The results were that two patients (15%) were cured, nine patients (70%) were improved (sterile prostatic fluid during therapy) but eventually relapsed, and two patients (15%) were unchanged by therapy. In our present study 19 patients (31.6%) were totally cured and 9 of 23 (39.1%) gram-negative organisms were permanently cleared from prostatic fluid; 8 of the 9 patients (42.1%) were improved but eventually relapsed with the same organism; 5 of the 19 patients (26.3%) were considered unchanged by therapy."}
{"id": "PMID:236821", "title": "Encephalitis after administration of live measles vaccine.", "content": "In a previously well child with no evidence of pre-existing immunologic defect a fatal encephalitis developed 10 days after administration of measles vaccine. There was pathologic evidence of an early viral encephalitis characterized by perivascular mononulcear infiltrates. Although the virus was not recovered, the diagnosis of a measles virus infection and encephalitis is supported by the postmortem findings of Warthin-Finkeldey cells in lymphoid tissues, an intranuclear inclusion in the brain and histologic changes of encephalitis.", "contents": "Encephalitis after administration of live measles vaccine. In a previously well child with no evidence of pre-existing immunologic defect a fatal encephalitis developed 10 days after administration of measles vaccine. There was pathologic evidence of an early viral encephalitis characterized by perivascular mononulcear infiltrates. Although the virus was not recovered, the diagnosis of a measles virus infection and encephalitis is supported by the postmortem findings of Warthin-Finkeldey cells in lymphoid tissues, an intranuclear inclusion in the brain and histologic changes of encephalitis."}
{"id": "PMID:236822", "title": "Characterization and subunit analysis of ferritin isolated from normal and malignant human liver.", "content": "Ferritin was purified from normal, fetal, and malignant liver tissue. Ferritin purified from hepatoma tissue migrated slightly faster than normal human liver ferritin in polyacrylamide gel electrophoresis. Hepatoma and fetal liver ferritin contained an acidic components in gel and liquid isoelectric focusing not found in normal liver ferritin. We have called it a carcinofetal isoferritin. The subunit compositions of ferritins purified from human liver cell carcinoma and normal liver were then compared. Both ferritin consisted of a subunit species with an identical molecular weight of approximately 18,500. A single subunit of similar molecular weight was also demonstrable after dissociation of 8 M urea and by gel filtration in urea. Two subunits were demonstrable in normal liver ferritin by means of acrylamide electrophoresis in 8 M urea in acid pH. The same two subunits were also demonstrable in ferritin isolated from human liver cell carcinoma. However, a third subunit, intermediate in charge between the two normal liver subunits, was demonstrable in different amounts in ferritins from two hepatomas. Ferritins from normal and malignant livers were immunologically indistinguishable. The tumor-specific acidic isoferritin was isolated and antisera were prepared. The isolated acidic isoferritin was found to be immunologically identical to normal liver isoferritins. It is concluded that the multiple isoferritins of the human liver ferritin consist of two subunits, which are identical in molecular weight but which differ in net charge. Ferritin, isolated from two human liver carcinoma tissues, was composed of the same two subunits and a third unique subunit. Different amounts of these subunits may account for the several normal isoferritins and a unique tumor-specific acid isoferritin found in hepatoma.", "contents": "Characterization and subunit analysis of ferritin isolated from normal and malignant human liver. Ferritin was purified from normal, fetal, and malignant liver tissue. Ferritin purified from hepatoma tissue migrated slightly faster than normal human liver ferritin in polyacrylamide gel electrophoresis. Hepatoma and fetal liver ferritin contained an acidic components in gel and liquid isoelectric focusing not found in normal liver ferritin. We have called it a carcinofetal isoferritin. The subunit compositions of ferritins purified from human liver cell carcinoma and normal liver were then compared. Both ferritin consisted of a subunit species with an identical molecular weight of approximately 18,500. A single subunit of similar molecular weight was also demonstrable after dissociation of 8 M urea and by gel filtration in urea. Two subunits were demonstrable in normal liver ferritin by means of acrylamide electrophoresis in 8 M urea in acid pH. The same two subunits were also demonstrable in ferritin isolated from human liver cell carcinoma. However, a third subunit, intermediate in charge between the two normal liver subunits, was demonstrable in different amounts in ferritins from two hepatomas. Ferritins from normal and malignant livers were immunologically indistinguishable. The tumor-specific acidic isoferritin was isolated and antisera were prepared. The isolated acidic isoferritin was found to be immunologically identical to normal liver isoferritins. It is concluded that the multiple isoferritins of the human liver ferritin consist of two subunits, which are identical in molecular weight but which differ in net charge. Ferritin, isolated from two human liver carcinoma tissues, was composed of the same two subunits and a third unique subunit. Different amounts of these subunits may account for the several normal isoferritins and a unique tumor-specific acid isoferritin found in hepatoma."}
{"id": "PMID:236823", "title": "Stability and dissociation of P3H4-1 Burkitt's lymphoma cell soluble complement-fixing antigen identified with human serum.", "content": "The soluble complement-fixing antigen of the P3HR-1 Burkitt's lymphoma cell line, identified with human serum containing antibody against Epstein-Barr virus viral capsid antigen, loses activity under a variety of conditions. The major characteristic reported here is retention of activity on exposure to specific physical or chemical conditions followed by loss of activity after subsequent neutral dialysis. Antigen of untreated cell lysates, which retains activity after dialysis against large volumes of neutral buffers or 0.14 M NaCl, will lose activity if the lysate is first heated to 56 degrees or if the lysate is exposed to acid perchlorate, and the resulting precipitate and supernatant are redialyzed separately to neutral pH. The P3HR-1 soluble complement-fixing antigen appears to be an aggregate including a labile, dissociable component.", "contents": "Stability and dissociation of P3H4-1 Burkitt's lymphoma cell soluble complement-fixing antigen identified with human serum. The soluble complement-fixing antigen of the P3HR-1 Burkitt's lymphoma cell line, identified with human serum containing antibody against Epstein-Barr virus viral capsid antigen, loses activity under a variety of conditions. The major characteristic reported here is retention of activity on exposure to specific physical or chemical conditions followed by loss of activity after subsequent neutral dialysis. Antigen of untreated cell lysates, which retains activity after dialysis against large volumes of neutral buffers or 0.14 M NaCl, will lose activity if the lysate is first heated to 56 degrees or if the lysate is exposed to acid perchlorate, and the resulting precipitate and supernatant are redialyzed separately to neutral pH. The P3HR-1 soluble complement-fixing antigen appears to be an aggregate including a labile, dissociable component."}
{"id": "PMID:236824", "title": "Changes in fine structure accompanying estrogen-induced tumorigenesis of Leydig cells in the mouse testis.", "content": "The development of estrogen-induced Leydig cell tumors in cryptorchid BALB/c mice was studied with the electron microscope. Changes in Leydig cell fine structure are apparent by 10 days after the s.c. implantation of a pellet of diethylstibestrol (DES). The smooth endoplasmic reticulum is diminished, and there is an increase in lipid droplets and free polysomes as compared with untreated cryptochid controls. These alterations persist as the Leydig cells proliferate to form focal areas of hyperplasia in the interstitial tissue. During this period of proliferation, activated macrophages containing large residual bodies appear among the Leydig cells. If DES treatment is continued for several months, malignant Leydig cell tumors, result. They are characterized by a nuclear and cytoplasmic pleomorphism of the Leydig cells and a decreased macrophage population. Virus-like particles are rarely seen within the cell during the period of tumorigenesis. Along with the reduction in smooth endoplasmic reticulum in the Leydig cells after DES treatment, evidence from the literature suggests that there is also a decrease in testosterone biosynthesis. However, it is not clear whether these two effect are correlated, since the level of the microsomal enzymes of steroid biosynthesis may vary independently of either the amount of smooth endoplasmic reticulum or the level of androgen secretion. The increase in lipid droplets seen in Leydig cells after DES treatment suggest the accumulation of precursors from the steroid biosynthetic pathway. The macrophages are though to represent scavenger cells, rather than a primary tumor cell population. The paucity of virus-like particles within altered Leydig cells implies that formed virus is not a prerequisite for tumorigenesis.", "contents": "Changes in fine structure accompanying estrogen-induced tumorigenesis of Leydig cells in the mouse testis. The development of estrogen-induced Leydig cell tumors in cryptorchid BALB/c mice was studied with the electron microscope. Changes in Leydig cell fine structure are apparent by 10 days after the s.c. implantation of a pellet of diethylstibestrol (DES). The smooth endoplasmic reticulum is diminished, and there is an increase in lipid droplets and free polysomes as compared with untreated cryptochid controls. These alterations persist as the Leydig cells proliferate to form focal areas of hyperplasia in the interstitial tissue. During this period of proliferation, activated macrophages containing large residual bodies appear among the Leydig cells. If DES treatment is continued for several months, malignant Leydig cell tumors, result. They are characterized by a nuclear and cytoplasmic pleomorphism of the Leydig cells and a decreased macrophage population. Virus-like particles are rarely seen within the cell during the period of tumorigenesis. Along with the reduction in smooth endoplasmic reticulum in the Leydig cells after DES treatment, evidence from the literature suggests that there is also a decrease in testosterone biosynthesis. However, it is not clear whether these two effect are correlated, since the level of the microsomal enzymes of steroid biosynthesis may vary independently of either the amount of smooth endoplasmic reticulum or the level of androgen secretion. The increase in lipid droplets seen in Leydig cells after DES treatment suggest the accumulation of precursors from the steroid biosynthetic pathway. The macrophages are though to represent scavenger cells, rather than a primary tumor cell population. The paucity of virus-like particles within altered Leydig cells implies that formed virus is not a prerequisite for tumorigenesis."}
{"id": "PMID:236825", "title": "Nuclear protein changes in rat hepatomas correlating with growth rate.", "content": "The nature of nuclear proteins that are soluble in 8 M urea-50 mM phosphate, pH 7.6, was compared in rat liver and Morris hepatomas, Isoelectric focusing, using carrier ampholytes for a pH gradient of 3.5 to 10, indicated that with increasing growth rate of the hepatomas there was a progressive tendency for a decrease in nonhistone nuclear proteins with isoelectric points in the range 7.5 to 8.9 and an increase in the range 5.1 to 6.7. Studies on the influence of time on the pH gradient revealed that a nonuniform drift provided a better resolution of the pH range 7.5 to 8.9 at 7 hr than at 24 hr, while the latter time for electrofocusing gave an improved resolution of the pH range 5.1 to 6.7 Polyarcylamide gel electrophoresis in a urea-acetic acid system showed that 8 M urea-50 mM phosphate; pH 7.6 extracted a small part of the histones from nuclei of both liver and hepatomas. There was less extraction of histones from the hepatoma nuclei, especially in two rapidly growing hepatomas with the most notable difference being seen in the lysine-rich H1 histone. The results suggested that in addition to qualitative or quantitative changes in nonhistone nuclear proteins in liver cancer there are alterations in the binding of histones to chromatin.", "contents": "Nuclear protein changes in rat hepatomas correlating with growth rate. The nature of nuclear proteins that are soluble in 8 M urea-50 mM phosphate, pH 7.6, was compared in rat liver and Morris hepatomas, Isoelectric focusing, using carrier ampholytes for a pH gradient of 3.5 to 10, indicated that with increasing growth rate of the hepatomas there was a progressive tendency for a decrease in nonhistone nuclear proteins with isoelectric points in the range 7.5 to 8.9 and an increase in the range 5.1 to 6.7. Studies on the influence of time on the pH gradient revealed that a nonuniform drift provided a better resolution of the pH range 7.5 to 8.9 at 7 hr than at 24 hr, while the latter time for electrofocusing gave an improved resolution of the pH range 5.1 to 6.7 Polyarcylamide gel electrophoresis in a urea-acetic acid system showed that 8 M urea-50 mM phosphate; pH 7.6 extracted a small part of the histones from nuclei of both liver and hepatomas. There was less extraction of histones from the hepatoma nuclei, especially in two rapidly growing hepatomas with the most notable difference being seen in the lysine-rich H1 histone. The results suggested that in addition to qualitative or quantitative changes in nonhistone nuclear proteins in liver cancer there are alterations in the binding of histones to chromatin."}
{"id": "PMID:236826", "title": "Altered distribution and excretion of N-1-methylnicotinamide in rats with Walker 256 carcinosarcoma.", "content": "Levels of nicotinamide and N-1-methylnicotinamide in serum, liver, and kidney as well as renal clearances and 24-hr urine levels of N-1-methylnicotinamide were compared in normal rats and rats bearing Walker 256 tumors. There was no significant difference between normal and tumor-bearing rats with regard to nicotinamide levels. With regard to N-1-methylnicotinamide, tumor-bearing rats had significantly lower serum and liver levels and significantly higher 24-hr urine levels and renal clearances. Walker 256 tumor tissue and liver and kidney from a normal and a tumor-bearing rat were separately examined for S-adenosylmethionine:nicotinamide methyltransferase activity. The specific activity in tumor tissue extract was greater than that in each liver extract, which, in turn, was much greater than the specific activity in each tissue (liver and kidney) from the tumor-bearing rat was equal to the specific activity in the corresponding tissue of the normal rat. S-adenosylmethionine:nicotinamide methyltransferase was obtained with 18-fold purification from a tissue extract of Walker 256 tumor. The enzyme activity required activation by thiols, and maximal activity was observed at pH 8.6. The Km's for the substrates, S-adenosylmethionine and nicotinamide, were 7.0 x 10--3 mM and 0.50 mM respectively. The Ki's for the products, S-adenosylhomocysteine and N-1-methylnicotinamide, were respectively, 25 x 10--3 mM and greater than 5 mM.", "contents": "Altered distribution and excretion of N-1-methylnicotinamide in rats with Walker 256 carcinosarcoma. Levels of nicotinamide and N-1-methylnicotinamide in serum, liver, and kidney as well as renal clearances and 24-hr urine levels of N-1-methylnicotinamide were compared in normal rats and rats bearing Walker 256 tumors. There was no significant difference between normal and tumor-bearing rats with regard to nicotinamide levels. With regard to N-1-methylnicotinamide, tumor-bearing rats had significantly lower serum and liver levels and significantly higher 24-hr urine levels and renal clearances. Walker 256 tumor tissue and liver and kidney from a normal and a tumor-bearing rat were separately examined for S-adenosylmethionine:nicotinamide methyltransferase activity. The specific activity in tumor tissue extract was greater than that in each liver extract, which, in turn, was much greater than the specific activity in each tissue (liver and kidney) from the tumor-bearing rat was equal to the specific activity in the corresponding tissue of the normal rat. S-adenosylmethionine:nicotinamide methyltransferase was obtained with 18-fold purification from a tissue extract of Walker 256 tumor. The enzyme activity required activation by thiols, and maximal activity was observed at pH 8.6. The Km's for the substrates, S-adenosylmethionine and nicotinamide, were 7.0 x 10--3 mM and 0.50 mM respectively. The Ki's for the products, S-adenosylhomocysteine and N-1-methylnicotinamide, were respectively, 25 x 10--3 mM and greater than 5 mM."}
{"id": "PMID:236827", "title": "Differential alkali-extraction of hemicellulose and hydroxyproline from non-delignified cell walls of lupin hypocotyls.", "content": "The extraction by alkali of hemicellulose polysaccharides and polymer hydroxyproline from non-delignified, primary cell-walls of lupin hypocotyls has been studied, using sequential extractions at 0 degrees and 18-22 degrees. 10% Aqueous potassium hydroxide at 0 degrees rapidly removed about two-thirds of the hemicellulose normally extracted in 10% KOH at 18-22 degrees and including nearly all of the hemicellulose-A. Little hydroxyproline was released at 0 degrees. When the temperature was subsequently raised to 18-22 degrees, the remaining 10% KOH-soluble hemicellulose, along with most of the hydroxyproline, was released. The monosaccharide composition of these fractions changed markedly with the time of extraction. Arabinose increased from 35% of the polysaccharide extracted during the first hour at 18-22 degrees to similar to 65% of the polysaccharide extracted between 16 and 20 h at 18-22 degrees. Hydroxyproline changed similarly as a proportion of polymer. The implications of these and other results are discussed in relation to polysaccharide and polymer extraction without prior delignification and to models of the primary cell-wall.", "contents": "Differential alkali-extraction of hemicellulose and hydroxyproline from non-delignified cell walls of lupin hypocotyls. The extraction by alkali of hemicellulose polysaccharides and polymer hydroxyproline from non-delignified, primary cell-walls of lupin hypocotyls has been studied, using sequential extractions at 0 degrees and 18-22 degrees. 10% Aqueous potassium hydroxide at 0 degrees rapidly removed about two-thirds of the hemicellulose normally extracted in 10% KOH at 18-22 degrees and including nearly all of the hemicellulose-A. Little hydroxyproline was released at 0 degrees. When the temperature was subsequently raised to 18-22 degrees, the remaining 10% KOH-soluble hemicellulose, along with most of the hydroxyproline, was released. The monosaccharide composition of these fractions changed markedly with the time of extraction. Arabinose increased from 35% of the polysaccharide extracted during the first hour at 18-22 degrees to similar to 65% of the polysaccharide extracted between 16 and 20 h at 18-22 degrees. Hydroxyproline changed similarly as a proportion of polymer. The implications of these and other results are discussed in relation to polysaccharide and polymer extraction without prior delignification and to models of the primary cell-wall."}
{"id": "PMID:236828", "title": "Purification and properties of coffee-bean alpha-D-galactosidase.", "content": "A purification method for alpha-D-galactosidase from Coffea canephora is described. Two enzymes, alpha-D-galactosidases I and II, having molecular weights of 28,000 and 36,500, respectively, were found and extensively purified. The reaction mechanism of alpha-D-galactosidase II was studied. The enzyme hydrolyzed aryl and alkyl alpha-D-galactopyranosides and was severely inhibited by excess of these substrates. No inhibition occurred with raffinose. The influence of para substituents on the reaction rate of phenyl alpha-D-galactopyranosides, the effect of added alcohols, and the non-competitive inhibition by methyl alpha-D-galactopyranoside were investigated. A two-step mechanism with the formation of an enzyme-galactosyl complex is proposed. With aryl galactopyranosides, the reaction of the enzyme-galactosyl complex with water is rate-limiting. Influences of the substituents on the inhibition constant were investigated by linear free-energy relationships, and significant correlations between this constant and electronic parameters could be calculated. The influence of pH on the reaction is complex.", "contents": "Purification and properties of coffee-bean alpha-D-galactosidase. A purification method for alpha-D-galactosidase from Coffea canephora is described. Two enzymes, alpha-D-galactosidases I and II, having molecular weights of 28,000 and 36,500, respectively, were found and extensively purified. The reaction mechanism of alpha-D-galactosidase II was studied. The enzyme hydrolyzed aryl and alkyl alpha-D-galactopyranosides and was severely inhibited by excess of these substrates. No inhibition occurred with raffinose. The influence of para substituents on the reaction rate of phenyl alpha-D-galactopyranosides, the effect of added alcohols, and the non-competitive inhibition by methyl alpha-D-galactopyranoside were investigated. A two-step mechanism with the formation of an enzyme-galactosyl complex is proposed. With aryl galactopyranosides, the reaction of the enzyme-galactosyl complex with water is rate-limiting. Influences of the substituents on the inhibition constant were investigated by linear free-energy relationships, and significant correlations between this constant and electronic parameters could be calculated. The influence of pH on the reaction is complex."}
{"id": "PMID:236829", "title": "The structure of Klebsiella serotype II capsular polysaccharide.", "content": "Using periodate oxidation, methylation analysis, the characterization of oligosaccharides obtained by partial acid hydrolysis, p.m.r. spectroscopy, and analytical ultracentrifugation, the structure of the (mildly alkali-treated) Klebsiella serotype 11 capusular polysaccharide has been elucidated. The tetrasaccharide repeating-unit comprises the sequence yields 3)-beta-D-Glcp-(1 yields 3)-beta-D-GlcUAp-(1 yields 3)-alpha-D-Galp-(1 yields with a 4,6-O-(1-carboxyethylidene)-alpha-D-galactosyl residue linked to O-4 of the glucuronic acid residue. The structural basis for some serological cross-reactions of the Klebseilla K11 antigen is discussed, and it is shown that rabbit antisera against the Klebsiella K11 test-strain predominantly contain K agglutinins specific for branch-terminal 4,6-O-(1-carboxyethylidene)-D-galactose.", "contents": "The structure of Klebsiella serotype II capsular polysaccharide. Using periodate oxidation, methylation analysis, the characterization of oligosaccharides obtained by partial acid hydrolysis, p.m.r. spectroscopy, and analytical ultracentrifugation, the structure of the (mildly alkali-treated) Klebsiella serotype 11 capusular polysaccharide has been elucidated. The tetrasaccharide repeating-unit comprises the sequence yields 3)-beta-D-Glcp-(1 yields 3)-beta-D-GlcUAp-(1 yields 3)-alpha-D-Galp-(1 yields with a 4,6-O-(1-carboxyethylidene)-alpha-D-galactosyl residue linked to O-4 of the glucuronic acid residue. The structural basis for some serological cross-reactions of the Klebseilla K11 antigen is discussed, and it is shown that rabbit antisera against the Klebsiella K11 test-strain predominantly contain K agglutinins specific for branch-terminal 4,6-O-(1-carboxyethylidene)-D-galactose."}
{"id": "PMID:236830", "title": "Bacteriophage-borne enzymes in carbohydrate chemistry. Part I. On the glycanase activity associated with particles of Klebsiella bacteriophage No. 11.", "content": "The preparation and use of particles of Klebsiella bacteriophage No. 11 are described. A glycanase activity associated with the viruses catalyses the depolymerization of (alkali-treated) Klebsiella serotype 11 capsular polysaccharide, ultimately to a mixture of oligosaccharides consisting of one or two repeating units. Mainly glucosidic bonds are hydrolysed. The substrate specificity of the viral enzyme has been characterized by using derivatives of serotype-11 polysaccharide, as well as 81 heterologous, bacterial, capsular glycans. It is concluded that the glycanase will (at least) also depolymerize all polysaccharides containing the unsubstituted chain-trisaccharide repeating-unit of its natural substrate.", "contents": "Bacteriophage-borne enzymes in carbohydrate chemistry. Part I. On the glycanase activity associated with particles of Klebsiella bacteriophage No. 11. The preparation and use of particles of Klebsiella bacteriophage No. 11 are described. A glycanase activity associated with the viruses catalyses the depolymerization of (alkali-treated) Klebsiella serotype 11 capsular polysaccharide, ultimately to a mixture of oligosaccharides consisting of one or two repeating units. Mainly glucosidic bonds are hydrolysed. The substrate specificity of the viral enzyme has been characterized by using derivatives of serotype-11 polysaccharide, as well as 81 heterologous, bacterial, capsular glycans. It is concluded that the glycanase will (at least) also depolymerize all polysaccharides containing the unsubstituted chain-trisaccharide repeating-unit of its natural substrate."}
{"id": "PMID:236831", "title": "Studies on the structure and mechanism of an exo-(1 yields 3)-beta-D-glucanase from Basidiomycete QM806.", "content": "A method for the large-scale production of a (1 yields 3)-beta-D-glucan glucohydrolase (EC 3.2.1.58) from the culture filtrate of Basidiomycete QM806 is described. The final preparation is homogeneous by disc electrophoresis under non-dissociating and denaturing conditions, by ultracentrifugation, and by isoelectric focusing. Various physical and chemical characteristics of the enzyme have been determined, including terminal amino acid residues, extinction coefficient, and stability to pH extremes. The N-terminal amino acids are leucine and serine (Sanger's method) and the C-terminal amino acids are alanine, serine, and glycine (hydrazinolysis). pH profile studies show that no group titrating in the region 2.5-8 is directly involved with substrate binding and that a single group having a pKa of 6.5 is involved in the catalysis. Photooxidation of the enzyme caused rapid inactivation. The pH-dependence of this photooxidation, and amino acid analysis of the photooxidized enzyme, indicate that decomposition of histidine is probably responsible for the loss of activity. Other chemical modifications performed were: treatment with hydrogen peroxide under acidic conditions, esterification with diphenyldiazomethane, and oxidation with N-bromosuccinimide. Oxidation with N-bromosuccinimide indicated that a tryptophan side-chain is involved in, but not necessary for, the catalytic activity.", "contents": "Studies on the structure and mechanism of an exo-(1 yields 3)-beta-D-glucanase from Basidiomycete QM806. A method for the large-scale production of a (1 yields 3)-beta-D-glucan glucohydrolase (EC 3.2.1.58) from the culture filtrate of Basidiomycete QM806 is described. The final preparation is homogeneous by disc electrophoresis under non-dissociating and denaturing conditions, by ultracentrifugation, and by isoelectric focusing. Various physical and chemical characteristics of the enzyme have been determined, including terminal amino acid residues, extinction coefficient, and stability to pH extremes. The N-terminal amino acids are leucine and serine (Sanger's method) and the C-terminal amino acids are alanine, serine, and glycine (hydrazinolysis). pH profile studies show that no group titrating in the region 2.5-8 is directly involved with substrate binding and that a single group having a pKa of 6.5 is involved in the catalysis. Photooxidation of the enzyme caused rapid inactivation. The pH-dependence of this photooxidation, and amino acid analysis of the photooxidized enzyme, indicate that decomposition of histidine is probably responsible for the loss of activity. Other chemical modifications performed were: treatment with hydrogen peroxide under acidic conditions, esterification with diphenyldiazomethane, and oxidation with N-bromosuccinimide. Oxidation with N-bromosuccinimide indicated that a tryptophan side-chain is involved in, but not necessary for, the catalytic activity."}
{"id": "PMID:236833", "title": "Ultrastructural study of crystalloids in sertoli cells of the normal, intersex and experimental cryptorchid swine.", "content": "Spindle- or needle-shaped crystalloids are observed in Sertoli cells of the intersex and experimental cryptorchid swine in the light and electron microscopes. Small crystalloids are also observed in Sertoli cells of the normal swine only by electron microscopy. These crystalloids consist of fine filaments. The filaments are about 5 nm in diameter and arranged parallel to the long axis of the drystalloid. In cross sections of the crystalloid, the close backing of the filaments shows hexagonal arrays. The interfilamentous distance is about 5 nm. In all animals, bundles of short filaments, which are 5nm in diameter, are observed in the basal part of the Sertoli cells. Ultrastructural similarities among the crystalloids, the bundles of fine filaments, and the filamentous layer in the junctional specialization of the Sertoli cell are shown. These morphological similarities suggest that the crystalloids are formed by the aggregation of the bundles in the Sertoli cells of azoospermic testes.", "contents": "Ultrastructural study of crystalloids in sertoli cells of the normal, intersex and experimental cryptorchid swine. Spindle- or needle-shaped crystalloids are observed in Sertoli cells of the intersex and experimental cryptorchid swine in the light and electron microscopes. Small crystalloids are also observed in Sertoli cells of the normal swine only by electron microscopy. These crystalloids consist of fine filaments. The filaments are about 5 nm in diameter and arranged parallel to the long axis of the drystalloid. In cross sections of the crystalloid, the close backing of the filaments shows hexagonal arrays. The interfilamentous distance is about 5 nm. In all animals, bundles of short filaments, which are 5nm in diameter, are observed in the basal part of the Sertoli cells. Ultrastructural similarities among the crystalloids, the bundles of fine filaments, and the filamentous layer in the junctional specialization of the Sertoli cell are shown. These morphological similarities suggest that the crystalloids are formed by the aggregation of the bundles in the Sertoli cells of azoospermic testes."}
{"id": "PMID:236834", "title": "D-valine as a selective agent for normal human and rodent epithelial cells in culture.", "content": "A nutrient medium has been developed to enable the growth of normal epithelial cells while selectively inhibiting fibroblast proliferation. In this medium, D-valine is substituted for L-valine; and only those cells containing D-amino acid oxidase can convert the D-amino acid into its essential L-enantiomer. The ability to select for cells with this enzyme has enabled us to maintain epithelial cell populations free from fibroblast overgrowth. The presence of D-amino acid oxidase has been histochemically confirmed in the epithelial cells selected from renal cell suspensions and explants. The ability to proliferate in the selective medium is transmitted to the clonal progeny of these cells. Moreover, epithelial cell proliferation of this medium indicates the presence of D-amino acid oxidase, which we have detected in tissues where it had not previously been reported-fetal human kidney, lung, and cord. Fibroblasts will not grow in the selective medium, but will proliferate normally if the product of the D-amino acid oxidase reaction is supplied.", "contents": "D-valine as a selective agent for normal human and rodent epithelial cells in culture. A nutrient medium has been developed to enable the growth of normal epithelial cells while selectively inhibiting fibroblast proliferation. In this medium, D-valine is substituted for L-valine; and only those cells containing D-amino acid oxidase can convert the D-amino acid into its essential L-enantiomer. The ability to select for cells with this enzyme has enabled us to maintain epithelial cell populations free from fibroblast overgrowth. The presence of D-amino acid oxidase has been histochemically confirmed in the epithelial cells selected from renal cell suspensions and explants. The ability to proliferate in the selective medium is transmitted to the clonal progeny of these cells. Moreover, epithelial cell proliferation of this medium indicates the presence of D-amino acid oxidase, which we have detected in tissues where it had not previously been reported-fetal human kidney, lung, and cord. Fibroblasts will not grow in the selective medium, but will proliferate normally if the product of the D-amino acid oxidase reaction is supplied."}
{"id": "PMID:236835", "title": "\"Superinduction\" of tyrosine aminotransferase by actinomycin D: a reevaluation.", "content": "Reexamination of the effects of actinomycin D (AMD) on the intracellular level and rate of synthesis of tyrosine aminotransferase (TAT) in hepatoma tissue culture (HTC) cells reveals that much apparent controversy can be resolved with acknowledgment of the multi-faceted nature of this inhibitor's action. AMD can slow overall protein synthesis and inhibit the degradation of both TAT and its mRNA as well as block the synthesis of RNA. The extent of these secondary actions of the inhibitor depend somewhat upon the growth condition of the cells. The effects of cordycepin (3'-deoxyadenosine) on the metabolism of TAT and its mRNA are also complex, but differ in several respects from those of AMD.", "contents": "\"Superinduction\" of tyrosine aminotransferase by actinomycin D: a reevaluation. Reexamination of the effects of actinomycin D (AMD) on the intracellular level and rate of synthesis of tyrosine aminotransferase (TAT) in hepatoma tissue culture (HTC) cells reveals that much apparent controversy can be resolved with acknowledgment of the multi-faceted nature of this inhibitor's action. AMD can slow overall protein synthesis and inhibit the degradation of both TAT and its mRNA as well as block the synthesis of RNA. The extent of these secondary actions of the inhibitor depend somewhat upon the growth condition of the cells. The effects of cordycepin (3'-deoxyadenosine) on the metabolism of TAT and its mRNA are also complex, but differ in several respects from those of AMD."}
{"id": "PMID:236836", "title": "Interaction of cortisol with the neural retina of the chick embryo in culture.", "content": "The uptake of cortisol and the kinetics of hormone-receptor interaction in the cytosol and cell nucleus were investigated in the intact tissue in organ culture. Cortisol is concentrated by the neural retina. The accumulation of the free steroid is temperature dependent but the effect of temperature decreases with the increase of cortisol in medium. Cortisol binding to specific receptors in the cytosol shows a sigmoidal type of kinetics which correlates well with the kinetics of glutamine-synthetase induction by cortisol. The temperature dependent translocation of the receptor-hormone complexes to the nuclei and the effect of detergents on the binding to nuclei are presented.", "contents": "Interaction of cortisol with the neural retina of the chick embryo in culture. The uptake of cortisol and the kinetics of hormone-receptor interaction in the cytosol and cell nucleus were investigated in the intact tissue in organ culture. Cortisol is concentrated by the neural retina. The accumulation of the free steroid is temperature dependent but the effect of temperature decreases with the increase of cortisol in medium. Cortisol binding to specific receptors in the cytosol shows a sigmoidal type of kinetics which correlates well with the kinetics of glutamine-synthetase induction by cortisol. The temperature dependent translocation of the receptor-hormone complexes to the nuclei and the effect of detergents on the binding to nuclei are presented."}
{"id": "PMID:236839", "title": "Vascular responses to prostaglandin F 2 alpha in isolated cat lungs.", "content": "Changes in perfusion pressure in response to graded doses of prostaglandin F 2 alpha (PGF 2 alpha) were measured during both forward and retrograde perfusion of isolated cat lungs perfused at a constant flow rate. During forward perfusion, PGF 2 alpha produced a dose-dependent increase in pulmonary artery pressure and a decrease in lung fluid volume. During retrograde perfusion, PGF 2 alpha also produced a dose-dependent increase in perfusion pressure; however, the dose required was fivefold greater than that needed to produce an identical change in pressure during forward perfusion. In addition, during retrograde perfusion, the lung fluid volume increased in response to PGF 2 alpha. These results suggest that the major site of activity of PGF 2 alpha is on the arterial side of the pulmonary vascular bed and that inactivation of PGF 2 alpha by the lung occurs primarily distal to this arterial site of vasomotion. The changes in perfusion pressure in response to PGF 2 alpha were markedly dependent on pH and oxygen tension (Po-2), being abolished by severe alkalosis and potentiated by both acidosis and hypoxia. In contrast, neither serotonin nor norepinephrine exhibited such a pH or Po-2 dependency. Since the ratio of the forward response to the retrograde response was not decreased by alterations of pH or Po-2, their influence on the responses appears to be through interaction at the site of vascular activity rather than through alteration of the rate of prostaglandin inactivation.", "contents": "Vascular responses to prostaglandin F 2 alpha in isolated cat lungs. Changes in perfusion pressure in response to graded doses of prostaglandin F 2 alpha (PGF 2 alpha) were measured during both forward and retrograde perfusion of isolated cat lungs perfused at a constant flow rate. During forward perfusion, PGF 2 alpha produced a dose-dependent increase in pulmonary artery pressure and a decrease in lung fluid volume. During retrograde perfusion, PGF 2 alpha also produced a dose-dependent increase in perfusion pressure; however, the dose required was fivefold greater than that needed to produce an identical change in pressure during forward perfusion. In addition, during retrograde perfusion, the lung fluid volume increased in response to PGF 2 alpha. These results suggest that the major site of activity of PGF 2 alpha is on the arterial side of the pulmonary vascular bed and that inactivation of PGF 2 alpha by the lung occurs primarily distal to this arterial site of vasomotion. The changes in perfusion pressure in response to PGF 2 alpha were markedly dependent on pH and oxygen tension (Po-2), being abolished by severe alkalosis and potentiated by both acidosis and hypoxia. In contrast, neither serotonin nor norepinephrine exhibited such a pH or Po-2 dependency. Since the ratio of the forward response to the retrograde response was not decreased by alterations of pH or Po-2, their influence on the responses appears to be through interaction at the site of vascular activity rather than through alteration of the rate of prostaglandin inactivation."}
{"id": "PMID:236840", "title": "\"Prorenin\" in human plasma?", "content": "An increase in plasma renin activity was demonstrated in plasma from normal subjects and most patients with essential hypertension after prolonged storage of the plasma at -20 degrees C. No change in renin substrate concentration was observed after storage for 12 months, and the rate of angiotensin generation during incubation with a fixed amount of added human renin was not increased. It therefore seems unlikely that the observed increase in renin activity was due to changes in plasma activators or inhibitors. The data are consistent with the activation of an inactive form of renin, tentatively called \"prorenin\" in normal subjects averaged from 1 to 2 ng/ml/hr, and did not change during sodium deprivation. However, three of four patients studied who had low-renin essential hypertension secreted abnormally large amounts of \"prorenin\" in response to sodium depletion. In these patients, subsequent sodium administration was associated with a return of \"prorenin\" to baseline levels.", "contents": "\"Prorenin\" in human plasma? An increase in plasma renin activity was demonstrated in plasma from normal subjects and most patients with essential hypertension after prolonged storage of the plasma at -20 degrees C. No change in renin substrate concentration was observed after storage for 12 months, and the rate of angiotensin generation during incubation with a fixed amount of added human renin was not increased. It therefore seems unlikely that the observed increase in renin activity was due to changes in plasma activators or inhibitors. The data are consistent with the activation of an inactive form of renin, tentatively called \"prorenin\" in normal subjects averaged from 1 to 2 ng/ml/hr, and did not change during sodium deprivation. However, three of four patients studied who had low-renin essential hypertension secreted abnormally large amounts of \"prorenin\" in response to sodium depletion. In these patients, subsequent sodium administration was associated with a return of \"prorenin\" to baseline levels."}
{"id": "PMID:236841", "title": "Dissociation between renin and arterial pressure responses to beta-adrenergic blockade in human essential hypertension.", "content": "Studies were carried out in 69 patients with essential hypertension to examine the relationship between changes in plasma renin activity (PRA) and arterial pressure (BP) in response to a beta-adrenergic blocking agent, propranolol. PRA had no consistent relationship with BP during treatment, either in patients receiving propranolol alone (r = 0.12) or in those receiving a combination of diuretics and propranolol (r = 0.18). Furthermore, long-term beta-adrenergic blockade failed to inhibit increases of PRA induced by diuretics or rapid sodium depletion. These results indicate that (1) beta-adrenergic blockade can reduce BP by mechanisms other than PRA suppression; and (2) the beta-adrenergic nervous system is important, but not essential, for renin release.", "contents": "Dissociation between renin and arterial pressure responses to beta-adrenergic blockade in human essential hypertension. Studies were carried out in 69 patients with essential hypertension to examine the relationship between changes in plasma renin activity (PRA) and arterial pressure (BP) in response to a beta-adrenergic blocking agent, propranolol. PRA had no consistent relationship with BP during treatment, either in patients receiving propranolol alone (r = 0.12) or in those receiving a combination of diuretics and propranolol (r = 0.18). Furthermore, long-term beta-adrenergic blockade failed to inhibit increases of PRA induced by diuretics or rapid sodium depletion. These results indicate that (1) beta-adrenergic blockade can reduce BP by mechanisms other than PRA suppression; and (2) the beta-adrenergic nervous system is important, but not essential, for renin release."}
{"id": "PMID:236842", "title": "Dopamine induced relaxation of isolated canine renal, mesenteric, and femoral arteries contracted with prostaglandin F2-alpha.", "content": "The purpose of this investigation was to develop a system for studying the effects of dopamine on isolated blood vessels. Canine renal, mesenteric, and small femoral arteries (less than 1 mm outside diameter) were exposed to phenoxybenzamine 10-5 M for one hour and contracted with prostaglandin F2-alpha. Cumulative concentrations of dopamine ranging from 10-6 to 10-4 M caused dose-related relaxation of the arteries. Propranolol 10-6 M did not affect the relaxation in concentrations which markedly antagonized the effects of isoproterenol. Large femoral arteries (greater than 1 mm outside diameter) did not relax with similar concentrations of dopamine. N-methyldopamine (epinine) produced similar relaxation; 3-methoxytyramine was inactive. Specific antagonism could not be demonstrated by the postulated dopamine antagonists-haloperidol, chlorpromazine, apomorphine, or bulbocapnine-in concentrations up to 10-5 M. Higher concentration of these agents could not be used because they caused the arteries to relax. This study demonstrated that PGF2-alpha-contracted arteries pretreated with phenoxybenzamine are suitable for further investigations of putative dopamine agonists and antagonists.", "contents": "Dopamine induced relaxation of isolated canine renal, mesenteric, and femoral arteries contracted with prostaglandin F2-alpha. The purpose of this investigation was to develop a system for studying the effects of dopamine on isolated blood vessels. Canine renal, mesenteric, and small femoral arteries (less than 1 mm outside diameter) were exposed to phenoxybenzamine 10-5 M for one hour and contracted with prostaglandin F2-alpha. Cumulative concentrations of dopamine ranging from 10-6 to 10-4 M caused dose-related relaxation of the arteries. Propranolol 10-6 M did not affect the relaxation in concentrations which markedly antagonized the effects of isoproterenol. Large femoral arteries (greater than 1 mm outside diameter) did not relax with similar concentrations of dopamine. N-methyldopamine (epinine) produced similar relaxation; 3-methoxytyramine was inactive. Specific antagonism could not be demonstrated by the postulated dopamine antagonists-haloperidol, chlorpromazine, apomorphine, or bulbocapnine-in concentrations up to 10-5 M. Higher concentration of these agents could not be used because they caused the arteries to relax. This study demonstrated that PGF2-alpha-contracted arteries pretreated with phenoxybenzamine are suitable for further investigations of putative dopamine agonists and antagonists."}
{"id": "PMID:236843", "title": "Effects of glucose, insulin and potassium infusion on tissue metabolic changes within first hour of myocardial infarction in the baboon.", "content": "The effects of infusions of glucose, insulin and potassium (GIK) on the heart tissue metabolic changes found in adult baboons 60 min after coronary artery ligation were studied. Biopsies taken from 11 baboons without coronary artery ligation gave control values. A second group of 46 baboons had coronary artery ligation. A third group of 17 baboons received an infusion of KCl after coronary artery ligation. A fourth group of 26 baboons received infusion of GIK. Coronary artery ligation resulted in the expected fall of ATP, creatine phosphate, glycogen, tissue (K+/Na+) ratio, and tissue pH, and rise of inorganic phosphate, lactare, lactate/pyruvate ratio and alpha-glycerophosphate in the infarction zones. Compared with ligation, additional infusions of GIK approximately doubled the contents of creatine phosphate and glycogen in the infarct zones, increased the content of ATP in the central infarct zone, and decreased the content of inorganic phosphate in the peripheral infarct zone. Other GIK effects were that the tissue (K+/Na+) ratio rose in the peripheral infarct zone, and the content of both glycogen and lactate rose in the peri-infarct and non-ischemic zones; the pH of tissue homogenates did not decrease. KCl infusions had few effects compared with the ligation group. GIK infusions exerted a beneficial effect when compared with infusions of KCl in that tissue creatine phosphate rose in the peripheral infarct and nonischemic zones; the tissue K+/Na+ ratio rose in the peripheral infarct, peri-infarct, and nonischemic zones; and the lactate/pyruvate ratio fell in the infarct zone. It is proposed that GIK counteracted early tissue metabolic deterioration in the infarcting baboon heart.", "contents": "Effects of glucose, insulin and potassium infusion on tissue metabolic changes within first hour of myocardial infarction in the baboon. The effects of infusions of glucose, insulin and potassium (GIK) on the heart tissue metabolic changes found in adult baboons 60 min after coronary artery ligation were studied. Biopsies taken from 11 baboons without coronary artery ligation gave control values. A second group of 46 baboons had coronary artery ligation. A third group of 17 baboons received an infusion of KCl after coronary artery ligation. A fourth group of 26 baboons received infusion of GIK. Coronary artery ligation resulted in the expected fall of ATP, creatine phosphate, glycogen, tissue (K+/Na+) ratio, and tissue pH, and rise of inorganic phosphate, lactare, lactate/pyruvate ratio and alpha-glycerophosphate in the infarction zones. Compared with ligation, additional infusions of GIK approximately doubled the contents of creatine phosphate and glycogen in the infarct zones, increased the content of ATP in the central infarct zone, and decreased the content of inorganic phosphate in the peripheral infarct zone. Other GIK effects were that the tissue (K+/Na+) ratio rose in the peripheral infarct zone, and the content of both glycogen and lactate rose in the peri-infarct and non-ischemic zones; the pH of tissue homogenates did not decrease. KCl infusions had few effects compared with the ligation group. GIK infusions exerted a beneficial effect when compared with infusions of KCl in that tissue creatine phosphate rose in the peripheral infarct and nonischemic zones; the tissue K+/Na+ ratio rose in the peripheral infarct, peri-infarct, and nonischemic zones; and the lactate/pyruvate ratio fell in the infarct zone. It is proposed that GIK counteracted early tissue metabolic deterioration in the infarcting baboon heart."}
{"id": "PMID:236844", "title": "Calibration of ion-selective electrodes for use in biological fluids.", "content": "We measured electromotive force at 37 degrees C with pH, sodium glass, valinomycin, and the Simon calcium electrodes in synthetic electrolyte mixtures simulating serum, in cells both with and without liquid junction. Evidently these electrodes respond in a near-Nernstian manner to changes in concentration of the ion sensed. We su-gest that such mixtures may serve as calibrating standards for ion-selective electrodes in clinical analysis. The effect of ionic strength on electrode response can be accounted for almost wholly by alterations in the activity coefficients. The lanthanum fluoride electrode activity coefficients. The lanthanum fluoride electrode shows promise as a reliable reference in cells without liquid junction.", "contents": "Calibration of ion-selective electrodes for use in biological fluids. We measured electromotive force at 37 degrees C with pH, sodium glass, valinomycin, and the Simon calcium electrodes in synthetic electrolyte mixtures simulating serum, in cells both with and without liquid junction. Evidently these electrodes respond in a near-Nernstian manner to changes in concentration of the ion sensed. We su-gest that such mixtures may serve as calibrating standards for ion-selective electrodes in clinical analysis. The effect of ionic strength on electrode response can be accounted for almost wholly by alterations in the activity coefficients. The lanthanum fluoride electrode activity coefficients. The lanthanum fluoride electrode shows promise as a reliable reference in cells without liquid junction."}
{"id": "PMID:236845", "title": "Quantitation of free, total, and antibody-bound insulin in insulin-treated diabetics.", "content": "We describe a simplified method for measuring free, total, and antibody-bound insulin in insulin-treated patients in whom antibodies to insulin are present. The free, active insulin is extracted from the serum with a polyethylene glycol solution. Total insulin is extracted from the serum with a polyethylene glycol solution after dissociation of the antibody-antigen complex with dilute HCI. Aliquots of the extracts are used in the radioimmunoassay system. The figure for antibody-bound insulin is the difference between the total and free insulin values and reflects the concentration of insulin antibodies present. A commercially available (\"Phadebas\") radioimmunoassay for immunoreactive insulin was used to quantitate the insulin present in the two extracts. Recovery of added insulin averaged 85% for the free insulin and 87%for the total insulin.", "contents": "Quantitation of free, total, and antibody-bound insulin in insulin-treated diabetics. We describe a simplified method for measuring free, total, and antibody-bound insulin in insulin-treated patients in whom antibodies to insulin are present. The free, active insulin is extracted from the serum with a polyethylene glycol solution. Total insulin is extracted from the serum with a polyethylene glycol solution after dissociation of the antibody-antigen complex with dilute HCI. Aliquots of the extracts are used in the radioimmunoassay system. The figure for antibody-bound insulin is the difference between the total and free insulin values and reflects the concentration of insulin antibodies present. A commercially available (\"Phadebas\") radioimmunoassay for immunoreactive insulin was used to quantitate the insulin present in the two extracts. Recovery of added insulin averaged 85% for the free insulin and 87%for the total insulin."}
{"id": "PMID:236846", "title": "Enzyme activities of NADPH-forming metabolic pathways in normal and leukemic leukocytes.", "content": "With respect to the enzymes of NADPH-forming metabolic pathways in human leukocytes: (a) Glucose-6-phosphate dehydrogenase and phosphogluconate dehydrogenase (decarboxylating) were less active in leukocytes (mostly myeloblasts) from eight patients with acute myeloblastic leukemia (I) than in leukocytes (mostly granulocytes) from 16 normal subjects (II). (b) Of the enzymes of the citrate cleavage pathway, ATP citrate lyase and malate dehydrogenase (decarboxylating) (NADP+) were virtually absent in the cells studied. (c) Isocitrate dehydrogenase (NADP+), aspartate aminotransferase, and alanine aminotransferase, which, together with the much more active malate dehydrogenase, constitute a newly proposed NADPH-forming metabolic cycle, showed a higher activity in I than in II or III, and therefore could compensate, as concerns NADPH-generation, for the low activity of pentose cycle dehydrogenases. We are not sure whether the enzymatic characteristic of I cells is attributable to their immaturity or to their leukemic nature.", "contents": "Enzyme activities of NADPH-forming metabolic pathways in normal and leukemic leukocytes. With respect to the enzymes of NADPH-forming metabolic pathways in human leukocytes: (a) Glucose-6-phosphate dehydrogenase and phosphogluconate dehydrogenase (decarboxylating) were less active in leukocytes (mostly myeloblasts) from eight patients with acute myeloblastic leukemia (I) than in leukocytes (mostly granulocytes) from 16 normal subjects (II). (b) Of the enzymes of the citrate cleavage pathway, ATP citrate lyase and malate dehydrogenase (decarboxylating) (NADP+) were virtually absent in the cells studied. (c) Isocitrate dehydrogenase (NADP+), aspartate aminotransferase, and alanine aminotransferase, which, together with the much more active malate dehydrogenase, constitute a newly proposed NADPH-forming metabolic cycle, showed a higher activity in I than in II or III, and therefore could compensate, as concerns NADPH-generation, for the low activity of pentose cycle dehydrogenases. We are not sure whether the enzymatic characteristic of I cells is attributable to their immaturity or to their leukemic nature."}
{"id": "PMID:236847", "title": "Colorimetric enzymatic determination of serum total carbon dioxide, as applied to the Vickers Multichannel 300 discrete analyzer.", "content": "Phosphoenolpyruvate carbosylase (EC 4.1.1.31) has been used in developing a simple, inexpensive colorimetric assay for serum total carbon dioxide in an open system. The oxaloacetate formed by the action of the enzyme on bicarbonate and phosphoenolpyruvate is measured by use of the diazonium salt of Fast Violet B. Interferences from billirubin, pyruvate, and drugs are negligible. Acetoacetate interference is significant only in highly ketotic samples, and a serum blank corrects for it. Serum protein interference is equivalent to 3.3 plus or minus 1.25 mmol of CO2 per liter and hence is sufficiently constant to be corrected for by use of a serum standard or serum blank. The method has been applied to the Vickers M-300 and D-300 systems and within-batch standard deviations of plus or minus 0.1 to plus or minus 0.6 mmol/liter have been observed. Excellent correlation with orthodox techniques has been obtained.", "contents": "Colorimetric enzymatic determination of serum total carbon dioxide, as applied to the Vickers Multichannel 300 discrete analyzer. Phosphoenolpyruvate carbosylase (EC 4.1.1.31) has been used in developing a simple, inexpensive colorimetric assay for serum total carbon dioxide in an open system. The oxaloacetate formed by the action of the enzyme on bicarbonate and phosphoenolpyruvate is measured by use of the diazonium salt of Fast Violet B. Interferences from billirubin, pyruvate, and drugs are negligible. Acetoacetate interference is significant only in highly ketotic samples, and a serum blank corrects for it. Serum protein interference is equivalent to 3.3 plus or minus 1.25 mmol of CO2 per liter and hence is sufficiently constant to be corrected for by use of a serum standard or serum blank. The method has been applied to the Vickers M-300 and D-300 systems and within-batch standard deviations of plus or minus 0.1 to plus or minus 0.6 mmol/liter have been observed. Excellent correlation with orthodox techniques has been obtained."}
{"id": "PMID:236848", "title": "A kinetic study on the influence of the parameters in the determination of inorganic phosphate by the molybdenum blue reaction.", "content": "Parameters which influence the initial rate of formation of phosphomolybdenum blue from phosphate, molybdate, polyvinylpyrrolidone and o-phenylenediamine were investigated. From kinetic data it is concluded that polyvinylpyrrolidone not only acts as a protective colloid, but that it takes part in the reaction and a reaction mechanism is proposed dealing with the stoichiometry of polyvinylpyrrolidone. A rate procedure for the determination of inorganic phosphate in serum and urine, based on this study, is given. Deproteinization of samples is not necessary. The method is rapid requiring one minute for quantitative readings. Because of this short period there is hardly any hydrolysis of organic phosphate esters. As the rate of color development is determined blanks can be omitted. Turbid samples may be analysed with little error.", "contents": "A kinetic study on the influence of the parameters in the determination of inorganic phosphate by the molybdenum blue reaction. Parameters which influence the initial rate of formation of phosphomolybdenum blue from phosphate, molybdate, polyvinylpyrrolidone and o-phenylenediamine were investigated. From kinetic data it is concluded that polyvinylpyrrolidone not only acts as a protective colloid, but that it takes part in the reaction and a reaction mechanism is proposed dealing with the stoichiometry of polyvinylpyrrolidone. A rate procedure for the determination of inorganic phosphate in serum and urine, based on this study, is given. Deproteinization of samples is not necessary. The method is rapid requiring one minute for quantitative readings. Because of this short period there is hardly any hydrolysis of organic phosphate esters. As the rate of color development is determined blanks can be omitted. Turbid samples may be analysed with little error."}
{"id": "PMID:236849", "title": "Cathodic oxygen consumption and electrically induced osteogenesis.", "content": "Small amounts of electric current stimulate bone formation in the region of a cathode. The purpose of this experiment is to compare changes in oxygen and hydroxyl ion concentration that occur at the cathode at current levels known to be capable of inducing osteogenesis (10-20 muamps) with those changes that occur at current levels known to be toxic to bone (100 muamps). An oxygen consumption chamber containing an oxygen electrode is fitted with two stainless steel electrodes which are connected to a constant current source. At the cathode, with a current of 100 muamps, oxygen is consumed at nearly stoichiometric rates. At higher current (100 muamps) levels, cathodic oxygen consumption gives way to hydrogen evolution. Cathodic hydroxyl ion production is directly proportional to current. It is concluded from these in vitro experiments that at 10-20 muamps the oxygen tension in the vicinity of the cathode is lowered and the pH is moderately increased. At 100 muamps the oxygen tension is not lowered, but the pH is increased dramatically. If these same changes occur in the vicinity of a cathode in vivo, then lowering the local tissue oxygen tension and raising the local pH may be mechanisms operative in electrically induced bone formation.", "contents": "Cathodic oxygen consumption and electrically induced osteogenesis. Small amounts of electric current stimulate bone formation in the region of a cathode. The purpose of this experiment is to compare changes in oxygen and hydroxyl ion concentration that occur at the cathode at current levels known to be capable of inducing osteogenesis (10-20 muamps) with those changes that occur at current levels known to be toxic to bone (100 muamps). An oxygen consumption chamber containing an oxygen electrode is fitted with two stainless steel electrodes which are connected to a constant current source. At the cathode, with a current of 100 muamps, oxygen is consumed at nearly stoichiometric rates. At higher current (100 muamps) levels, cathodic oxygen consumption gives way to hydrogen evolution. Cathodic hydroxyl ion production is directly proportional to current. It is concluded from these in vitro experiments that at 10-20 muamps the oxygen tension in the vicinity of the cathode is lowered and the pH is moderately increased. At 100 muamps the oxygen tension is not lowered, but the pH is increased dramatically. If these same changes occur in the vicinity of a cathode in vivo, then lowering the local tissue oxygen tension and raising the local pH may be mechanisms operative in electrically induced bone formation."}
{"id": "PMID:236900", "title": "[Differences in the quality of vaccinia viruses with normal and abnormal post-vaccination course (with neurological complications) (author's transl)].", "content": "Conventional vaccinia strains were cultured at different temperatures, because it is known that vaccinia viruses which are human pathogens grow even at higher temperatures (41 degrees C). Neither the vaccination strains nor the vaccinia viruses which were isolated from vaccination vesicles after normal (n equals 7) or abnormal primary vaccinations (n equals 2) multiplied at higher incubation temperatures; Vaccinia viruses isolated from CSF of four patients with neurological complications behaved differently. Uninhibited growth at 41 degrees C (with high infection titres) suggest that the viruses isolated from CSF were vaccinia variants with abnormal characteristics. Accordingly, these variants morphologically formed plaques in Vero-cell cultures which were two to three times larger than those of vaccinia viruses obtained from CSF of primary vaccinated cases after only moderately severe general reactions, and which on temperature test responded like the viruses used in the original vaccination.", "contents": "[Differences in the quality of vaccinia viruses with normal and abnormal post-vaccination course (with neurological complications) (author's transl)]. Conventional vaccinia strains were cultured at different temperatures, because it is known that vaccinia viruses which are human pathogens grow even at higher temperatures (41 degrees C). Neither the vaccination strains nor the vaccinia viruses which were isolated from vaccination vesicles after normal (n equals 7) or abnormal primary vaccinations (n equals 2) multiplied at higher incubation temperatures; Vaccinia viruses isolated from CSF of four patients with neurological complications behaved differently. Uninhibited growth at 41 degrees C (with high infection titres) suggest that the viruses isolated from CSF were vaccinia variants with abnormal characteristics. Accordingly, these variants morphologically formed plaques in Vero-cell cultures which were two to three times larger than those of vaccinia viruses obtained from CSF of primary vaccinated cases after only moderately severe general reactions, and which on temperature test responded like the viruses used in the original vaccination."}
{"id": "PMID:236901", "title": "The oxidation of arsenite in seawater.", "content": "The oxidation rate of arsenite in seawater is very slow. Of the parameters investigated which might affect this rate the most important were temperature, initial arsenite concentration, salinity and pH. An empirical rate expression was developed from experimental data which led to a prediction that the natural rate of oxidation in the ocean is about 0.023 micromoles of As(III) per liter each year. This value is about twice the natural concentration of arsenite; the only mechanism which seems able to account for the continued presence of arsenite is biological reduction of arsenate.", "contents": "The oxidation of arsenite in seawater. The oxidation rate of arsenite in seawater is very slow. Of the parameters investigated which might affect this rate the most important were temperature, initial arsenite concentration, salinity and pH. An empirical rate expression was developed from experimental data which led to a prediction that the natural rate of oxidation in the ocean is about 0.023 micromoles of As(III) per liter each year. This value is about twice the natural concentration of arsenite; the only mechanism which seems able to account for the continued presence of arsenite is biological reduction of arsenate."}
{"id": "PMID:236902", "title": "Enzymatic degradation of protein mixtures.", "content": "The rate of protein enzymatic degradation in a mixture is slower than that of single proteins. In a mixture of haemoglobin or casein with protamine, the release of tyrosine by trypsin and chymotrypsin A is slower. A slower rate in the release of arginine from protamine occurs only in mixtures with haemoglobin. The inhibition of enzymatic degradation of proteins in a mixture is due to formation of intermolecular associations and to changes in their spacial structure.", "contents": "Enzymatic degradation of protein mixtures. The rate of protein enzymatic degradation in a mixture is slower than that of single proteins. In a mixture of haemoglobin or casein with protamine, the release of tyrosine by trypsin and chymotrypsin A is slower. A slower rate in the release of arginine from protamine occurs only in mixtures with haemoglobin. The inhibition of enzymatic degradation of proteins in a mixture is due to formation of intermolecular associations and to changes in their spacial structure."}
{"id": "PMID:236903", "title": "Deoxyribonuclease in human parotid saliva.", "content": "Deoxyribonuclease (EC 3.1.4.5, EC 3.1.4.6) activities in human parotid saliva were examined by microdisc electrophoresis. Three fractions, differing in their electrophoretic mobility and in their optimal incubation conditions, were characterized. The various enzyme activities were tested at pH 5.0 in 100 mmol with l-minus 1 Na-acetate buffer or at pH 7.04 in 100 mmol with l-minus 1 Tris-HCl-buffer in the presence of different combinations of MgCl(2), CaCl(2), EDTA, and Na(2)SO(4).", "contents": "Deoxyribonuclease in human parotid saliva. Deoxyribonuclease (EC 3.1.4.5, EC 3.1.4.6) activities in human parotid saliva were examined by microdisc electrophoresis. Three fractions, differing in their electrophoretic mobility and in their optimal incubation conditions, were characterized. The various enzyme activities were tested at pH 5.0 in 100 mmol with l-minus 1 Na-acetate buffer or at pH 7.04 in 100 mmol with l-minus 1 Tris-HCl-buffer in the presence of different combinations of MgCl(2), CaCl(2), EDTA, and Na(2)SO(4)."}
{"id": "PMID:236904", "title": "Influence of possible in situ ionic environment on kinetics of purified citrate synthase from an osmoconformer sea anemone, Bunedosoma cavernata.", "content": "Kinetics of utilization of acetyl coenzyme A by citrate synthase of a sea anemone, an osmoconformer, were compared with those of citrate synthases of various osmoregulators. The Kms of the latter enzymes were substantially increased by higher concentrations of salt and the enzyme exhibited hyperbolic substrate saturation curves. Citrate synthase from sea anemone, on the other hand, exhibited allosteric kinetics and minimal effects of salt on its Km. We suggest that the adaptive advantage of this enzymic property to a sedentary osmoconforming organism such as sea anemone is obvious since the osmoregulating creatures are apparently unable to maintain an appropriate low ionic environment in situ and thus probably the Km of their citrate synthases at a low level.", "contents": "Influence of possible in situ ionic environment on kinetics of purified citrate synthase from an osmoconformer sea anemone, Bunedosoma cavernata. Kinetics of utilization of acetyl coenzyme A by citrate synthase of a sea anemone, an osmoconformer, were compared with those of citrate synthases of various osmoregulators. The Kms of the latter enzymes were substantially increased by higher concentrations of salt and the enzyme exhibited hyperbolic substrate saturation curves. Citrate synthase from sea anemone, on the other hand, exhibited allosteric kinetics and minimal effects of salt on its Km. We suggest that the adaptive advantage of this enzymic property to a sedentary osmoconforming organism such as sea anemone is obvious since the osmoregulating creatures are apparently unable to maintain an appropriate low ionic environment in situ and thus probably the Km of their citrate synthases at a low level."}
{"id": "PMID:236905", "title": "Separation of two L-glutamine-hydroxylamine glutamyltransferases from rat liver.", "content": "The purification of glutamine synthetase (GS) from rat liver demonstrates that a small portion of glutamine-hydroxylamine-glutamyltransferase activity (GT) remains associated with GS activity (GT(S)). As GS is purified from the water extract, the ratio between GT(S) activity (GT(T)) is left to be extracted by KC1 from the pellet and, on further purification, appears to be independent of GS activity. Subtle differences in pH optimum, substrate requirement and reaction rates on addition of cofactors and amino acids in vitro and in responses to hormonal stimuli in vivo indicate that the glutamine transfer reaction may be catalyzed by two distinguishable proteins; only the minor component may be identical to GS.", "contents": "Separation of two L-glutamine-hydroxylamine glutamyltransferases from rat liver. The purification of glutamine synthetase (GS) from rat liver demonstrates that a small portion of glutamine-hydroxylamine-glutamyltransferase activity (GT) remains associated with GS activity (GT(S)). As GS is purified from the water extract, the ratio between GT(S) activity (GT(T)) is left to be extracted by KC1 from the pellet and, on further purification, appears to be independent of GS activity. Subtle differences in pH optimum, substrate requirement and reaction rates on addition of cofactors and amino acids in vitro and in responses to hormonal stimuli in vivo indicate that the glutamine transfer reaction may be catalyzed by two distinguishable proteins; only the minor component may be identical to GS."}
{"id": "PMID:236906", "title": "Effect of free and conjugated bile salts on alpha-amylase activity.", "content": "The effect of individual bile salts on alpha-amylase hydrolysis of Cibachron Blue starch was studied at pH 6.0. With sodium cholate, taurocholate and taurodeoxycholate, enzyme activity was increased to 150-160 percent of the control value, at a concentration of similar to 1 mmol/l bile salt. The increased activity extended up to 4 mmol/l. The bile salts sodium deoxycholate and taurochenodeoxycholate exerted activation and inhibition depending on the concentration. With deoxycholate (0.75 mmol/l), activation (150 percent) was evident, while inhibition was apparent above 2.5 mmol/l. With taurochenodeoxycholate maximum activity (135 percent) was observed at 0.25 mmol/l, while inhibition was evident above 1.5 mmol/l. Chenodeoxycholate and lithocholate exerted marked inhibition at concentrations as low as 0.5 mmol/l. Inhibition of alpha-amylase by chenodeoxycholate was competitive with both soluble and insoluble starch substrates. Since the pH of the jejunum is in the region of 6.0 the phenomenon of activation and inhibition of alpha-amylase by bile salts at this pH could be of physiological significance.", "contents": "Effect of free and conjugated bile salts on alpha-amylase activity. The effect of individual bile salts on alpha-amylase hydrolysis of Cibachron Blue starch was studied at pH 6.0. With sodium cholate, taurocholate and taurodeoxycholate, enzyme activity was increased to 150-160 percent of the control value, at a concentration of similar to 1 mmol/l bile salt. The increased activity extended up to 4 mmol/l. The bile salts sodium deoxycholate and taurochenodeoxycholate exerted activation and inhibition depending on the concentration. With deoxycholate (0.75 mmol/l), activation (150 percent) was evident, while inhibition was apparent above 2.5 mmol/l. With taurochenodeoxycholate maximum activity (135 percent) was observed at 0.25 mmol/l, while inhibition was evident above 1.5 mmol/l. Chenodeoxycholate and lithocholate exerted marked inhibition at concentrations as low as 0.5 mmol/l. Inhibition of alpha-amylase by chenodeoxycholate was competitive with both soluble and insoluble starch substrates. Since the pH of the jejunum is in the region of 6.0 the phenomenon of activation and inhibition of alpha-amylase by bile salts at this pH could be of physiological significance."}
{"id": "PMID:236907", "title": "Enzyme catalyzed hydrolysis of inorganic pyrophosphate. Current view of problems in characterization of PP1-phosphohydrolytic activity associated with alkaline phosphatases (EC 3.1.3.1).", "content": "A survey of the hydrolytic activity of alkaline phosphatase (EC 3.1.3.1) reveals that PP1, like phosphomonoesters, can serve as substrate in vitro. This pp1-phosphohydrolytic activity can be distinguished from PP1-phosphohydrolytic activities of inorganic pyrophosphatases (EC 3.6.1.1) and glucose-6-phosphatase (EC 3.1.3.9) by several criteria. Discrimination among these hydrolytic enzymes is possible by their dependence on variation of pH and of magnesium to PP1 ratios in the assay solutions. The true substrates and modifiers are not simply PP1 and magnesium, but the equilibrium species in mixtures of these two. The physiological significance of each of the three enzymes is not predictable from their differential efficiency as catalysts of PP1-hydrolysis in vitro.", "contents": "Enzyme catalyzed hydrolysis of inorganic pyrophosphate. Current view of problems in characterization of PP1-phosphohydrolytic activity associated with alkaline phosphatases (EC 3.1.3.1). A survey of the hydrolytic activity of alkaline phosphatase (EC 3.1.3.1) reveals that PP1, like phosphomonoesters, can serve as substrate in vitro. This pp1-phosphohydrolytic activity can be distinguished from PP1-phosphohydrolytic activities of inorganic pyrophosphatases (EC 3.6.1.1) and glucose-6-phosphatase (EC 3.1.3.9) by several criteria. Discrimination among these hydrolytic enzymes is possible by their dependence on variation of pH and of magnesium to PP1 ratios in the assay solutions. The true substrates and modifiers are not simply PP1 and magnesium, but the equilibrium species in mixtures of these two. The physiological significance of each of the three enzymes is not predictable from their differential efficiency as catalysts of PP1-hydrolysis in vitro."}
{"id": "PMID:236908", "title": "The calcium paradox: a reaffirmation.", "content": "Perfusion of isolated rat hearts with a Ca-2+-containing medium, after a Ca2+-free perfusion period, results in an irreversible loss of electrical and mechanical activity of the heart, as well as a large release of intracellular components such as lactate dehydrogenase. These phenomena can be evoked, when hearts are perfused at a constant perfusion pressure or at a constant flow rate. Evidence is provided that recovery of the mechanical activity of the heart is not a requisite for lactate dehydrogenase release.", "contents": "The calcium paradox: a reaffirmation. Perfusion of isolated rat hearts with a Ca-2+-containing medium, after a Ca2+-free perfusion period, results in an irreversible loss of electrical and mechanical activity of the heart, as well as a large release of intracellular components such as lactate dehydrogenase. These phenomena can be evoked, when hearts are perfused at a constant perfusion pressure or at a constant flow rate. Evidence is provided that recovery of the mechanical activity of the heart is not a requisite for lactate dehydrogenase release."}
{"id": "PMID:236938", "title": "Mechanism of action of narcotics in the production of menstrual dysfunction in women.", "content": "The ability of morphine to block ovulation in animals prompted investigation of the frequency and mechanisms of menstrual abnormalities in women addicted to narcotic analgesics. Menstrual histories obtained from 76 former heroin addicts receiving daily methadone maintenance revealed that more than one-half of these women had experienced menstrual abnormalities while taking heroin or methadone. In order to determine the specific physiologic effects of narcotic analgesics on reproductive function, detailed endocrinologic studies were carried out in seven of these patients who complained of amenorrhea or irregular menses while receiving methadone. Four of the seven women manifested abnormalities of the control of gonadotropin secretion. Three of these four failed to exhibit cyclic gonadotropin release, as evidenced by an absence of increased levels of follicular phase follicle-stimulating hormone, midcycle gonadotropin peaks or luteal phase progesterone increments. In the fourth patient a prolonged follicular phase (30 days) of the menstrual cycle was detected. One of these four patients also had low basal gonadotropin levels and failed to exhibit luteinizing hormone increments greater than control levels in response to ethinyl estradiol (positive feedback). The remaining three women exhibited normal patterns of gonadotropin secretion during the observation period. In these women, menstrual bleeding occurred in response to withdrawal from luteal phase (10 to 20 ng/ml) progesterone levels and to exogenous ethinyl estradiol, suggesting normal uterine responsivity to progesterone and estrogen. Although not documented, it is likely that oligo-ovulation was the cause of the irregular menses in these three patients. Amenorrhea is commonly associated with methadone ingestion or heroin addiction and appears to be related to an alteration of the hypothalamic mechanisms controlling gonadotropin secretion. Tolerance to these effects of methadone may develop after chronic ingestion.", "contents": "Mechanism of action of narcotics in the production of menstrual dysfunction in women. The ability of morphine to block ovulation in animals prompted investigation of the frequency and mechanisms of menstrual abnormalities in women addicted to narcotic analgesics. Menstrual histories obtained from 76 former heroin addicts receiving daily methadone maintenance revealed that more than one-half of these women had experienced menstrual abnormalities while taking heroin or methadone. In order to determine the specific physiologic effects of narcotic analgesics on reproductive function, detailed endocrinologic studies were carried out in seven of these patients who complained of amenorrhea or irregular menses while receiving methadone. Four of the seven women manifested abnormalities of the control of gonadotropin secretion. Three of these four failed to exhibit cyclic gonadotropin release, as evidenced by an absence of increased levels of follicular phase follicle-stimulating hormone, midcycle gonadotropin peaks or luteal phase progesterone increments. In the fourth patient a prolonged follicular phase (30 days) of the menstrual cycle was detected. One of these four patients also had low basal gonadotropin levels and failed to exhibit luteinizing hormone increments greater than control levels in response to ethinyl estradiol (positive feedback). The remaining three women exhibited normal patterns of gonadotropin secretion during the observation period. In these women, menstrual bleeding occurred in response to withdrawal from luteal phase (10 to 20 ng/ml) progesterone levels and to exogenous ethinyl estradiol, suggesting normal uterine responsivity to progesterone and estrogen. Although not documented, it is likely that oligo-ovulation was the cause of the irregular menses in these three patients. Amenorrhea is commonly associated with methadone ingestion or heroin addiction and appears to be related to an alteration of the hypothalamic mechanisms controlling gonadotropin secretion. Tolerance to these effects of methadone may develop after chronic ingestion."}
{"id": "PMID:236939", "title": "Effects of hormonal treatments which alter ovum transport on beta-adrenoceptors of the rabbit oviduct.", "content": "Beta-Adrenoceptor activity of rabbit oviductal isthmus has been determined quantitatively in vitro in tissues isolated 24 and 72 hours after human chorionic gonadotropin injection and after two hormonal treatments known to accelerate (progesterone) and retard (estrogen) ovum transport. Under conditions in which ova are located at the ampullary-isthmic junction and distal isthmus, the isthmus demonstrates a low incidence of spontaneous activity in vitro, poor response to acetylcholine, low affinity of beta-adrenoceptors for isoproterenol, and low efficacy of isoproterenol to inhibit acetylcholine-induced contractions. Under conditions in which ova are passing into the uterus, the isthmus shows the converse of these parameters. These data support the hypotheses that the oviductal isthmus functions as an adrenergic sphincter and that the actions of progesterone and estrogen in altering ovum transport rates are at least partially mediated through changes in adrenoceptors.", "contents": "Effects of hormonal treatments which alter ovum transport on beta-adrenoceptors of the rabbit oviduct. Beta-Adrenoceptor activity of rabbit oviductal isthmus has been determined quantitatively in vitro in tissues isolated 24 and 72 hours after human chorionic gonadotropin injection and after two hormonal treatments known to accelerate (progesterone) and retard (estrogen) ovum transport. Under conditions in which ova are located at the ampullary-isthmic junction and distal isthmus, the isthmus demonstrates a low incidence of spontaneous activity in vitro, poor response to acetylcholine, low affinity of beta-adrenoceptors for isoproterenol, and low efficacy of isoproterenol to inhibit acetylcholine-induced contractions. Under conditions in which ova are passing into the uterus, the isthmus shows the converse of these parameters. These data support the hypotheses that the oviductal isthmus functions as an adrenergic sphincter and that the actions of progesterone and estrogen in altering ovum transport rates are at least partially mediated through changes in adrenoceptors."}
{"id": "PMID:236940", "title": "[Neuro-humoral interrelationships in ontogeny].", "content": "A.A. Ukhtomsky's ideas of the relationship between the electric and the humoral components of transmission of nervous impulses in thr organism, are considered.  The data obtained recently when studying synaptic transmission of excitation in the sympathetic ganglia of mammals during ontogeny are presented in corroboration of A.A. Ukhtomsky's ideas of that the humoral factors affect neural reactions changing the lability of substratum, which is manifested by the grade of polarization of cellular membrane to a certain critical extent.", "contents": "[Neuro-humoral interrelationships in ontogeny]. A.A. Ukhtomsky's ideas of the relationship between the electric and the humoral components of transmission of nervous impulses in thr organism, are considered.  The data obtained recently when studying synaptic transmission of excitation in the sympathetic ganglia of mammals during ontogeny are presented in corroboration of A.A. Ukhtomsky's ideas of that the humoral factors affect neural reactions changing the lability of substratum, which is manifested by the grade of polarization of cellular membrane to a certain critical extent."}
{"id": "PMID:236964", "title": "PLasma glucagon levels during rapid exsanguination with and without adrenergic blockade.", "content": "In eleven dogs made hypotensive by means of rapid exsanguination over a period of forty to seventy minutes, mean glucagon rose to a peak of 516 plus or minus (S.E.) 150 pg/ml. and mean glucose to a peak of 341 plus or minus 27 mg. per 100 ml. The hyperglucagonemia induced by exsanguination was substantially reduced, although not abolished, by propranolol infusion, but was not diminished by phentolamine, suggesting that it was largely a beta-adrenergic effect. Its possible contribution to survival during shock is considered.", "contents": "PLasma glucagon levels during rapid exsanguination with and without adrenergic blockade. In eleven dogs made hypotensive by means of rapid exsanguination over a period of forty to seventy minutes, mean glucagon rose to a peak of 516 plus or minus (S.E.) 150 pg/ml. and mean glucose to a peak of 341 plus or minus 27 mg. per 100 ml. The hyperglucagonemia induced by exsanguination was substantially reduced, although not abolished, by propranolol infusion, but was not diminished by phentolamine, suggesting that it was largely a beta-adrenergic effect. Its possible contribution to survival during shock is considered."}
{"id": "PMID:236971", "title": "Effect of pH on bile salt injury to mouse gastric mucosa. A light- and electron-microscopic study.", "content": "Bile salts break the gastric mucosal barrier. To explain this, the suggestion has been made that bile salts may disrupt surface epithelial cell membranes or break the tight junctions between cells, but appropriate ultrastructural studies are lacking. We therefore instilled control and bile salt-containing solutions into the stomachs of fasted mice at pH, 1, 3, 5, AND 7. Taurocholate (pKa equals 1.8) caused mucosal injury only at pH 1, whereas glycochenodeoxycholate (pKa equals 4.2) injured the mucosa at pH 1 and 3. By electron microscopy, areas of mild mucosal injury were characterized by clumping of nuclear chromatin and loss of cytoplasmic density within surface mucous cells. The apical cell membranes and tight junctions remained intact. In areas of severe damage surface cells were ruptured but tight junctions still appeared unbroken. These studies indicate that acid pH markedly augments the damaging effects of bile salts on mouse gastric mucosa. Moreover, as an initial step in the mechanism of bile salt-induced gastric injury, the nonionized moiety of a given bile salt which exists below its pKa may be important in altering the gastric surface epithelial cell in a way which allows the ingress of bile salt and/or hydrogen ion to cause intracellular damage.", "contents": "Effect of pH on bile salt injury to mouse gastric mucosa. A light- and electron-microscopic study. Bile salts break the gastric mucosal barrier. To explain this, the suggestion has been made that bile salts may disrupt surface epithelial cell membranes or break the tight junctions between cells, but appropriate ultrastructural studies are lacking. We therefore instilled control and bile salt-containing solutions into the stomachs of fasted mice at pH, 1, 3, 5, AND 7. Taurocholate (pKa equals 1.8) caused mucosal injury only at pH 1, whereas glycochenodeoxycholate (pKa equals 4.2) injured the mucosa at pH 1 and 3. By electron microscopy, areas of mild mucosal injury were characterized by clumping of nuclear chromatin and loss of cytoplasmic density within surface mucous cells. The apical cell membranes and tight junctions remained intact. In areas of severe damage surface cells were ruptured but tight junctions still appeared unbroken. These studies indicate that acid pH markedly augments the damaging effects of bile salts on mouse gastric mucosa. Moreover, as an initial step in the mechanism of bile salt-induced gastric injury, the nonionized moiety of a given bile salt which exists below its pKa may be important in altering the gastric surface epithelial cell in a way which allows the ingress of bile salt and/or hydrogen ion to cause intracellular damage."}
{"id": "PMID:236972", "title": "Failure of cholestyramine to prevent bile salt injury to mouse gastric mucosa.", "content": "Bile salts have been implicated in the pathogenesis of gastritis and gastric ulcer. Because the bile salt binding agent cholestyramine has been suggested as a possible therapy for gastric ulcer, we studied the effects of cholestyramine, in the form of Questran, on bile salt-induced injury to mouse gastric mucosa. Solutions of taurocholate or of glycochenodeoxycholate, with or without added Questran, were instilled into the stomachs of fasted mice at pH 1, 3, 5, and 7. Taurocholate damaged the mucosa only at pH 1, whereas glycochenodeoxycholate caused injury at pH 1 and 3. Questran failed to prevent mucosal damage by either bile salt. The ineffectiveness of cholestyramine to prevent injury may be due to the nonionized fraction of bile salts at pH's below their pKa's which will not be sequestered by the anion exchange resin. This phenomenon may help explain the insignificant effect of Qestran treatment in promoting healing of gastric ulcers in a previous clinical trial.", "contents": "Failure of cholestyramine to prevent bile salt injury to mouse gastric mucosa. Bile salts have been implicated in the pathogenesis of gastritis and gastric ulcer. Because the bile salt binding agent cholestyramine has been suggested as a possible therapy for gastric ulcer, we studied the effects of cholestyramine, in the form of Questran, on bile salt-induced injury to mouse gastric mucosa. Solutions of taurocholate or of glycochenodeoxycholate, with or without added Questran, were instilled into the stomachs of fasted mice at pH 1, 3, 5, and 7. Taurocholate damaged the mucosa only at pH 1, whereas glycochenodeoxycholate caused injury at pH 1 and 3. Questran failed to prevent mucosal damage by either bile salt. The ineffectiveness of cholestyramine to prevent injury may be due to the nonionized fraction of bile salts at pH's below their pKa's which will not be sequestered by the anion exchange resin. This phenomenon may help explain the insignificant effect of Qestran treatment in promoting healing of gastric ulcers in a previous clinical trial."}
{"id": "PMID:236976", "title": "Gene duplication as a mechanism of genetic adaptation in Saccharomyces cerevisiae.", "content": "It has been shown that specific mutations of the gene that codes for the general acid monophophatase (Aphtase) of S. cerevisiae can increase the affinity of this enzyme for beta-glycerophosphate (BGP) and thereby provide this organism with the capacity to exploit extremely low concentrations of this organic phosphate (Francis and Hansche 1973). In this report two additional avenues are demonstrated to be available to this organism for increasing its capacity to exploit low concentrations of organic phosphates. One avenue is through mutations that increase the amount of Aphtase that associates with the cell wall, where it catalizes the hydrolysis of exogenous organic phosphates. The other avenue is through duplication of the gene that codes for Aphtase, doubling the amount of Aphtase synthesized.--The spontaneous duplication of the structural gene of Aphtase and the incorporation of the duplicate into this experimental population as a means of exploiting low concentrations of exogenous organic phosphates provides direct support for the first step of the mechanism through which new metabolic functions are postulated to evolve.", "contents": "Gene duplication as a mechanism of genetic adaptation in Saccharomyces cerevisiae. It has been shown that specific mutations of the gene that codes for the general acid monophophatase (Aphtase) of S. cerevisiae can increase the affinity of this enzyme for beta-glycerophosphate (BGP) and thereby provide this organism with the capacity to exploit extremely low concentrations of this organic phosphate (Francis and Hansche 1973). In this report two additional avenues are demonstrated to be available to this organism for increasing its capacity to exploit low concentrations of organic phosphates. One avenue is through mutations that increase the amount of Aphtase that associates with the cell wall, where it catalizes the hydrolysis of exogenous organic phosphates. The other avenue is through duplication of the gene that codes for Aphtase, doubling the amount of Aphtase synthesized.--The spontaneous duplication of the structural gene of Aphtase and the incorporation of the duplicate into this experimental population as a means of exploiting low concentrations of exogenous organic phosphates provides direct support for the first step of the mechanism through which new metabolic functions are postulated to evolve."}
{"id": "PMID:236977", "title": "Isolation and study of mutants lacking a derepressible phosphatase in Chlamydomonas reinhardi.", "content": "In the green alga Chlamydomonas reinhardi, removal of inorganic phosphate from the culture medium results in the increase of phosphatase activity (derepression) in the wild-type (WT) strain as well as in a double mutant (P2Pa)) lacking the two main constitutive acid phosphatases. Following treatment of WT and P2Pa with N-methyl-N-nitro-N-nitrosoguanidine (MNNG), mutants were recovered which display very low phosphatase activities when grown in the absence of phosphate; as shown by electrophoresis, they lack one non-migrating phosphatase (PD mutants). This enzyme is active over a wide range of pH with an optimum at pH 7.5. The comparison of elctropherograms form WT and mutants grown on media with or without phosphate allowed us to provide a tentative definition of the pool of derepressible phosphatases in Chlamydomonas: in addition tothe neutral phosphatase lacking in PD mutants, Chlamydomonas produces two electrophoretic forms of alkaline phosphatase showing an optimal activity at pH 9.5.", "contents": "Isolation and study of mutants lacking a derepressible phosphatase in Chlamydomonas reinhardi. In the green alga Chlamydomonas reinhardi, removal of inorganic phosphate from the culture medium results in the increase of phosphatase activity (derepression) in the wild-type (WT) strain as well as in a double mutant (P2Pa)) lacking the two main constitutive acid phosphatases. Following treatment of WT and P2Pa with N-methyl-N-nitro-N-nitrosoguanidine (MNNG), mutants were recovered which display very low phosphatase activities when grown in the absence of phosphate; as shown by electrophoresis, they lack one non-migrating phosphatase (PD mutants). This enzyme is active over a wide range of pH with an optimum at pH 7.5. The comparison of elctropherograms form WT and mutants grown on media with or without phosphate allowed us to provide a tentative definition of the pool of derepressible phosphatases in Chlamydomonas: in addition tothe neutral phosphatase lacking in PD mutants, Chlamydomonas produces two electrophoretic forms of alkaline phosphatase showing an optimal activity at pH 9.5."}
{"id": "PMID:236981", "title": "Membranoproliferative glomerulonephritis with polyarteritis: a case report.", "content": "A case of membranoproliferative glomerulonephritis with polyarteritis is described. The patient was a 68 year old male who had the disease for about four months. A kidney biopsy specimen taken just before the patient died was studied by light, immunofluorescence, and electron microscopy. Splitting of the basement membrane, IgG, IgA, BlC, Clq, fibrinogen, and electron dense deposits were found in the glomeruli. It is considered that perhaps some cases of membranoproliferative glomerulonephritis are produced by circulating immune complexes.", "contents": "Membranoproliferative glomerulonephritis with polyarteritis: a case report. A case of membranoproliferative glomerulonephritis with polyarteritis is described. The patient was a 68 year old male who had the disease for about four months. A kidney biopsy specimen taken just before the patient died was studied by light, immunofluorescence, and electron microscopy. Splitting of the basement membrane, IgG, IgA, BlC, Clq, fibrinogen, and electron dense deposits were found in the glomeruli. It is considered that perhaps some cases of membranoproliferative glomerulonephritis are produced by circulating immune complexes."}
{"id": "PMID:236983", "title": "Tularaemia in the rat. I. The cellular basis on host resistance to infection.", "content": "Rats infected with the live vaccine strain (LVS) of Francisella tularensis develop in vivo and in vitro evidence of cellular hypersensitivity and a concomitant state of cellular resistance to infection. They key role of sensitized lymphocytes in cellular resistance was domonstrated in transfer experiments. Using this technique, it was shown that thoracic duct lymphocytes from Francisella immune donors conferred specific antimicrobial resistance on normal recipients, whereas antiserum afforded no protection whatsoever. Further evidence for the participation of sensitized lymphocytes in the host's defence emerged from experiments in which a comparative analysis was made of the immunogenic properties of living and heat-killed LVS organisms. Rats stimulated with the living parasite developed cellular hypersensitivity and specific antibodies. Throacic duct lymphocytes obtained from such animals could immunize adoptively. By comparison, rats stimulated with a substantially larger number of dead organisms failed to develop cellular hypersensitivity and their lymphocytes were devoid of protective activity. Dead organisms, however, provoked an antibody response similar to that observed in infected rats. The development of cellular hypersensitivity in Francisella-infected rats is associated with enhanced resistance to Listeria monocytogenes. This finding accords with the results of similar studies of infection immunity to other intracellular parasites, and implies that the expression of cellular resistance to F. tularensis is a cooperative venture involving specifically sensitized lymphocytes and non-specific inflammatory cells, presumably macrophages.", "contents": "Tularaemia in the rat. I. The cellular basis on host resistance to infection. Rats infected with the live vaccine strain (LVS) of Francisella tularensis develop in vivo and in vitro evidence of cellular hypersensitivity and a concomitant state of cellular resistance to infection. They key role of sensitized lymphocytes in cellular resistance was domonstrated in transfer experiments. Using this technique, it was shown that thoracic duct lymphocytes from Francisella immune donors conferred specific antimicrobial resistance on normal recipients, whereas antiserum afforded no protection whatsoever. Further evidence for the participation of sensitized lymphocytes in the host's defence emerged from experiments in which a comparative analysis was made of the immunogenic properties of living and heat-killed LVS organisms. Rats stimulated with the living parasite developed cellular hypersensitivity and specific antibodies. Throacic duct lymphocytes obtained from such animals could immunize adoptively. By comparison, rats stimulated with a substantially larger number of dead organisms failed to develop cellular hypersensitivity and their lymphocytes were devoid of protective activity. Dead organisms, however, provoked an antibody response similar to that observed in infected rats. The development of cellular hypersensitivity in Francisella-infected rats is associated with enhanced resistance to Listeria monocytogenes. This finding accords with the results of similar studies of infection immunity to other intracellular parasites, and implies that the expression of cellular resistance to F. tularensis is a cooperative venture involving specifically sensitized lymphocytes and non-specific inflammatory cells, presumably macrophages."}
{"id": "PMID:236984", "title": "Immunodeficiency in the chicken. III. Hypoplasia of bursal follicles following intravenous injection of embryos with lipopolysaccharide or allogeneic lymphocytes.", "content": "Intravenous injection of LPS or allogeneic lymphocytes resulted in impaired maturation of B cells within the bursa of chick embryos. A gradual decline in the sensitivity of embryos towards both agents was reflected by a decrease in the number and size of bursal follicles following injection between 10 and 15 days of embryonation. The hypoplasia of these follicles in embryos injected with lymphocytes on the 10th day was a more sensitive measure of graft-versus-host reaction than splenomegaly. The relevance of results with this model to the aetiology of immunodeficiency diseases has been briefly discussed.", "contents": "Immunodeficiency in the chicken. III. Hypoplasia of bursal follicles following intravenous injection of embryos with lipopolysaccharide or allogeneic lymphocytes. Intravenous injection of LPS or allogeneic lymphocytes resulted in impaired maturation of B cells within the bursa of chick embryos. A gradual decline in the sensitivity of embryos towards both agents was reflected by a decrease in the number and size of bursal follicles following injection between 10 and 15 days of embryonation. The hypoplasia of these follicles in embryos injected with lymphocytes on the 10th day was a more sensitive measure of graft-versus-host reaction than splenomegaly. The relevance of results with this model to the aetiology of immunodeficiency diseases has been briefly discussed."}
{"id": "PMID:236986", "title": "Radiosensitization of cultured mammalian cells by 5-iodouridine.", "content": "Radiosensitization of cultured mammalian cells was studied with halogenated pyrimidines, such as 5-iodouridine or 6-chloropurine, which have been shown to promote bacterial cell lethality when combined with gamma-irradiation. When Chinese hamster cells were exposed to gamma-rays to acidic pH values and the number of colonies was scored after 6 to 11 days of incubation, many more cells were inactivated in the presence of the drug than in its absence. This may be due to radiation-induced cytotoxic iodine radicals from the reagent in the case of 5-iodouridine, because the cells were inactivated efficiently only be contact with the previously-irradiated drug solution. The toxicity of the irradiated drug solution increased remarkably when the pH shifted to acidic side. The radiosensitization and the cytotoxic effects of gamma-irradiated drug solution were not found with 6-chloropurine. This may be the first observation on the lethal effect of chemical radicals on mammalian cells, and it is concluded that radiosensitization with 5-iodouridine does not require the drug incorporation into cellular DNA, at least under the conditions adopted in the present studies.", "contents": "Radiosensitization of cultured mammalian cells by 5-iodouridine. Radiosensitization of cultured mammalian cells was studied with halogenated pyrimidines, such as 5-iodouridine or 6-chloropurine, which have been shown to promote bacterial cell lethality when combined with gamma-irradiation. When Chinese hamster cells were exposed to gamma-rays to acidic pH values and the number of colonies was scored after 6 to 11 days of incubation, many more cells were inactivated in the presence of the drug than in its absence. This may be due to radiation-induced cytotoxic iodine radicals from the reagent in the case of 5-iodouridine, because the cells were inactivated efficiently only be contact with the previously-irradiated drug solution. The toxicity of the irradiated drug solution increased remarkably when the pH shifted to acidic side. The radiosensitization and the cytotoxic effects of gamma-irradiated drug solution were not found with 6-chloropurine. This may be the first observation on the lethal effect of chemical radicals on mammalian cells, and it is concluded that radiosensitization with 5-iodouridine does not require the drug incorporation into cellular DNA, at least under the conditions adopted in the present studies."}
{"id": "PMID:236990", "title": "Paradoxic aciduria in bovine metabolic alkalosis.", "content": "Cows with metabolic alkalosis secondary to abomasal displacement and other abomasal disorders were often found to excrete acidic urine. This paradoxic aciduria contradictsthe classical view that the pH of the urine may be used to estimate the acid-base status of the body. Data from bovine clinical patients with metabolic alkalosis, serum electrolyte changes, and paradoxic aciduria suggested that the balance of sodium potassium, and chloride in the body places limits on the kidneys' ability to regulate the acid-basebalance.", "contents": "Paradoxic aciduria in bovine metabolic alkalosis. Cows with metabolic alkalosis secondary to abomasal displacement and other abomasal disorders were often found to excrete acidic urine. This paradoxic aciduria contradictsthe classical view that the pH of the urine may be used to estimate the acid-base status of the body. Data from bovine clinical patients with metabolic alkalosis, serum electrolyte changes, and paradoxic aciduria suggested that the balance of sodium potassium, and chloride in the body places limits on the kidneys' ability to regulate the acid-basebalance."}
{"id": "PMID:236988", "title": "Effect of choleretics on biliary and urinary excretion of cholecystographic agents.", "content": "Two choleretic agents, taurocholate and cinchophen, were studied in the dog to determine their effect on both the biliary and urinary excretion of two related cholecystographic agents, iopanoic acid and iophenoxic acid.  Liver concentrations were determined on biopsies.  Trace amounts of radioactively labeled compounds were used for measurements.  The effect of the choleretic agent was specific for the cholecystographic compound.  Taurocholate increased both biliary and urinary excretion of iopanoic acid and decreased its intrahepatic level, but had no effect on iophenoxic acid.  Cinchophen had no effect on iopanoic acid but increased both biliary and urinary excretion of iophenoxic acid.  When examined against a pre-existing high rate of bile flow, the active choleretic increased, rather than decreased, the biliary concentration of the cholecystographic compound.  The increased excretion in both bile and urine cannot be attributed simply to the lessened concentration gradient from plasma to bile, as proposed by others.  The data are consistent with  a direct action of the choleretic agent on hepatic mechanisms, either to decrease intracellular binding or to alter the characteristics of transport.", "contents": "Effect of choleretics on biliary and urinary excretion of cholecystographic agents. Two choleretic agents, taurocholate and cinchophen, were studied in the dog to determine their effect on both the biliary and urinary excretion of two related cholecystographic agents, iopanoic acid and iophenoxic acid.  Liver concentrations were determined on biopsies.  Trace amounts of radioactively labeled compounds were used for measurements.  The effect of the choleretic agent was specific for the cholecystographic compound.  Taurocholate increased both biliary and urinary excretion of iopanoic acid and decreased its intrahepatic level, but had no effect on iophenoxic acid.  Cinchophen had no effect on iopanoic acid but increased both biliary and urinary excretion of iophenoxic acid.  When examined against a pre-existing high rate of bile flow, the active choleretic increased, rather than decreased, the biliary concentration of the cholecystographic compound.  The increased excretion in both bile and urine cannot be attributed simply to the lessened concentration gradient from plasma to bile, as proposed by others.  The data are consistent with  a direct action of the choleretic agent on hepatic mechanisms, either to decrease intracellular binding or to alter the characteristics of transport."}
{"id": "PMID:236989", "title": "Factitious changes in binding of oxygen to hemoglobin when based on extracellular pH in the presence of certain blood additives like radiographic contrast media.", "content": "Construction of oxygen-hemoglobin DISSOCIATION CURVES BASED ON EXTRACELLULAR PH and using blood tonometered with 5 per cent CO2, is misleading under certain experimental conditions.  These include the presence in blood of poorly penetrating non-ionic molecules like sucrose of poorly penetrating anionic aompounds like radiographic contrast materials.  False conclusions regarding the position of the oxygen-hemoglobin dissociation curve can result because of the disturbance of the normal pH gradient between plasma and red cell induced by such chemicals.", "contents": "Factitious changes in binding of oxygen to hemoglobin when based on extracellular pH in the presence of certain blood additives like radiographic contrast media. Construction of oxygen-hemoglobin DISSOCIATION CURVES BASED ON EXTRACELLULAR PH and using blood tonometered with 5 per cent CO2, is misleading under certain experimental conditions.  These include the presence in blood of poorly penetrating non-ionic molecules like sucrose of poorly penetrating anionic aompounds like radiographic contrast materials.  False conclusions regarding the position of the oxygen-hemoglobin dissociation curve can result because of the disturbance of the normal pH gradient between plasma and red cell induced by such chemicals."}
{"id": "PMID:236993", "title": "Purification and properties of leucine beta-naphthylamidase from rabbit small-intestinal mucosal cells.", "content": "Leucine beta-naphthylamidase associated with the microvilli membranes of rabbit small intestine was solubilized with papain [EC 3.4.22.2] and purified by Sephadex G-200 gel filtration, DEAE-cellulose column chromatography, passage through a column of Sepharose 4B coupled with anti-sucrase antibodies and preparative disc electrophoresis in polyacrylamide gel. The purified enzyme was homogeneous on ultracentrifugation and disc electrophoresis, but a double immunodiffusion test showed the presence of a minor component which was probably denatured enzyme. The molecular weight of the purified enzyme was estimated to be 225,000 by Sephadex G-200 gel filtration and the sedimentation coefficient (S-0-20, w) was found to be 6.90S. Purified enzyme required bovine serum albumin for maximal activity, perhaps for its protection from autodigestion. It hydrolyzed, in addition to L-leucine beta-naphthylamide, various L-amino acid beta-naphthylamides and dipeptides with a free alpha-amino group, but did not hydrolyze benzoyl-L-arginine beta-naphthylamide. Therefore, the purified enzyme is an aminopeptidase. Hg-2+ and Cu-2+ ions strongly inhibited the enzyme activity, but other metal ions and EDTA showed no or only slight effect. N-Ethylmaleimide exhibited a weak inhibition. Purified enzyme had an optimal pH and Km value for leucine beta-naphthylamide similar to those of enzymes from other sources. Antibodies against the purified enzyme were raised in guinea pigs. The antibodies obtained were found by double immunodiffusion to be specific for the enzyme. They precipitated the enzyme quantitatively and partially inhibited the enzyme activity.", "contents": "Purification and properties of leucine beta-naphthylamidase from rabbit small-intestinal mucosal cells. Leucine beta-naphthylamidase associated with the microvilli membranes of rabbit small intestine was solubilized with papain [EC 3.4.22.2] and purified by Sephadex G-200 gel filtration, DEAE-cellulose column chromatography, passage through a column of Sepharose 4B coupled with anti-sucrase antibodies and preparative disc electrophoresis in polyacrylamide gel. The purified enzyme was homogeneous on ultracentrifugation and disc electrophoresis, but a double immunodiffusion test showed the presence of a minor component which was probably denatured enzyme. The molecular weight of the purified enzyme was estimated to be 225,000 by Sephadex G-200 gel filtration and the sedimentation coefficient (S-0-20, w) was found to be 6.90S. Purified enzyme required bovine serum albumin for maximal activity, perhaps for its protection from autodigestion. It hydrolyzed, in addition to L-leucine beta-naphthylamide, various L-amino acid beta-naphthylamides and dipeptides with a free alpha-amino group, but did not hydrolyze benzoyl-L-arginine beta-naphthylamide. Therefore, the purified enzyme is an aminopeptidase. Hg-2+ and Cu-2+ ions strongly inhibited the enzyme activity, but other metal ions and EDTA showed no or only slight effect. N-Ethylmaleimide exhibited a weak inhibition. Purified enzyme had an optimal pH and Km value for leucine beta-naphthylamide similar to those of enzymes from other sources. Antibodies against the purified enzyme were raised in guinea pigs. The antibodies obtained were found by double immunodiffusion to be specific for the enzyme. They precipitated the enzyme quantitatively and partially inhibited the enzyme activity."}
{"id": "PMID:236994", "title": "pH jump-induced phosphorylation of adenosine diphosphate in thylakoidal membranes.", "content": "The kinetic properties of pH jump-induced phosphorylation in thylakoidal membranes of spinach chloroplasts were investigated, and the following results were obtained. 1. The pH jump-induced P incorporation proceeded linearly with time for at least 2 sec after the start of the reaction. Phosphate was incorporated mainly into ATP. The amounts of incorporation into ADP during 0.1 and 2.0 sec were 0.02 and 0.1 mole/400 moles chl, respectively. The amounts of P incorporation into ADP and the beta-position of ATP during a 2 sec reaction were less than 5 and 0.1% of the total amount of P incorporation, respectively. Even in the absence of added ADP, ATP was formed by the pH jump, but the amount was very small, i.e., less than 1% of that in the presence of a saturating amount of ADP. Formation of ATP was not enhanced by the addition of 0.1 mM AMP, instead of ADP. 2. The dependence of the rate of ATP formation, v, induced by a pH jump from 3.85 to 8.11 on the concentrations of ADP and Pi was given by v=Vopt/[1+psi1/[ADP]) (1 + psi2/[Pi)], where the values of the constants, Vopt, psi1, and psi2 were 14--20 moles/10-6 g chl/sec, 12.5-15 muM and 11-20 mM, respectively, at 0 degrees. 3. The dependence of v on the concentration of protons was given by v=Va/[1 + psi H-a/[H+,-a])-2], and v =Vb/[1 + ([H+,-b]/psiH-b)-2], in the acidic and basic phases, respectively. The values of the constants psi H-a and psi H-b were 10-5.7 and 10-7.9 M, respectively. 4. ATP formation was initiated by adding one of the substrates, ADP or Pi, at various times after after the pH jump in the presence of the other substrate. The rate decreased logarithmically with increase in the time between the pH jump and the start of the reaction. When phosphorylation was initiated by adding Pi after the pH jump in the presence of ADP, the decay constant of v was about 0.08 sec-1, which was one-third of that observed when the order of addition of ADP and Pi was reversed.", "contents": "pH jump-induced phosphorylation of adenosine diphosphate in thylakoidal membranes. The kinetic properties of pH jump-induced phosphorylation in thylakoidal membranes of spinach chloroplasts were investigated, and the following results were obtained. 1. The pH jump-induced P incorporation proceeded linearly with time for at least 2 sec after the start of the reaction. Phosphate was incorporated mainly into ATP. The amounts of incorporation into ADP during 0.1 and 2.0 sec were 0.02 and 0.1 mole/400 moles chl, respectively. The amounts of P incorporation into ADP and the beta-position of ATP during a 2 sec reaction were less than 5 and 0.1% of the total amount of P incorporation, respectively. Even in the absence of added ADP, ATP was formed by the pH jump, but the amount was very small, i.e., less than 1% of that in the presence of a saturating amount of ADP. Formation of ATP was not enhanced by the addition of 0.1 mM AMP, instead of ADP. 2. The dependence of the rate of ATP formation, v, induced by a pH jump from 3.85 to 8.11 on the concentrations of ADP and Pi was given by v=Vopt/[1+psi1/[ADP]) (1 + psi2/[Pi)], where the values of the constants, Vopt, psi1, and psi2 were 14--20 moles/10-6 g chl/sec, 12.5-15 muM and 11-20 mM, respectively, at 0 degrees. 3. The dependence of v on the concentration of protons was given by v=Va/[1 + psi H-a/[H+,-a])-2], and v =Vb/[1 + ([H+,-b]/psiH-b)-2], in the acidic and basic phases, respectively. The values of the constants psi H-a and psi H-b were 10-5.7 and 10-7.9 M, respectively. 4. ATP formation was initiated by adding one of the substrates, ADP or Pi, at various times after after the pH jump in the presence of the other substrate. The rate decreased logarithmically with increase in the time between the pH jump and the start of the reaction. When phosphorylation was initiated by adding Pi after the pH jump in the presence of ADP, the decay constant of v was about 0.08 sec-1, which was one-third of that observed when the order of addition of ADP and Pi was reversed."}
{"id": "PMID:236995", "title": "Purification and properties of elastolytic enzyme from Flavobacterium immotum.", "content": "Elastolytic enzyme was purified and crystallized from culture fluid of Flavobacterium immotum No. 9-35. The purified enzyme was homogeneous on polyacrylamide gel electrophoresis. The molecular weight was determined by Sephadex G-100 gel filtration to be 13,000. The isoelectric point was between pH 8.3 and 8.9. The optimum pH of the enzyme was 7.2 for elastolytic activity. The purified enzyme showed not only elastolytic activity, but also non-specific proteolytic activity against various other proteins. Milk-clotting activity was also observed. The enzyme did not act on keratin, collagen, or fourteen amino acid esters, including N-benzoyl-L-alanine methyl ester, N-benzoyl-L-arginine ethyl ester, and N-acetyl-L-tyrosine ethyl ester, which were typical substrates of pancreatic elastase [EC 3.4.21.11], trypsin [EC 3.4.21.4], and chymotrypsin [EC 3.4.21.1], respectively. However, the enzyme selectively hydrolyzed elastin when both elastin and albumin were present in the reaction mixture. The enzyme was inhibited by o-phenanthroline and various heavy metals such as cadmium, lead, zinc, and mercury. Various inhibitors, such as diisopropyl phosphofluoridate, tosyl-L-lysine chloromethyl ketone, tosyl-L-phenylalanine chloromethyl ketone, trypsin inhibitor, iodoacetamide, etc., had no effect on the elastolytic activity.", "contents": "Purification and properties of elastolytic enzyme from Flavobacterium immotum. Elastolytic enzyme was purified and crystallized from culture fluid of Flavobacterium immotum No. 9-35. The purified enzyme was homogeneous on polyacrylamide gel electrophoresis. The molecular weight was determined by Sephadex G-100 gel filtration to be 13,000. The isoelectric point was between pH 8.3 and 8.9. The optimum pH of the enzyme was 7.2 for elastolytic activity. The purified enzyme showed not only elastolytic activity, but also non-specific proteolytic activity against various other proteins. Milk-clotting activity was also observed. The enzyme did not act on keratin, collagen, or fourteen amino acid esters, including N-benzoyl-L-alanine methyl ester, N-benzoyl-L-arginine ethyl ester, and N-acetyl-L-tyrosine ethyl ester, which were typical substrates of pancreatic elastase [EC 3.4.21.11], trypsin [EC 3.4.21.4], and chymotrypsin [EC 3.4.21.1], respectively. However, the enzyme selectively hydrolyzed elastin when both elastin and albumin were present in the reaction mixture. The enzyme was inhibited by o-phenanthroline and various heavy metals such as cadmium, lead, zinc, and mercury. Various inhibitors, such as diisopropyl phosphofluoridate, tosyl-L-lysine chloromethyl ketone, tosyl-L-phenylalanine chloromethyl ketone, trypsin inhibitor, iodoacetamide, etc., had no effect on the elastolytic activity."}
{"id": "PMID:236996", "title": "Interaction of aflatoxin B1 with DNA.", "content": "The interaction of aflatoxin B1 with DNA was investigated. In the presence of native DNA the absorption spectrum of the toxin showed an obvious spectral shift in the region of 300-420 nm with an isosbestic point at 376 nm. DNA-bound aflatoxin is hydrolyzed in alkaline media more easily than the free toxin. The hydrolized form has a labile structure and can decompose further. The bound toxins are easily dissociated by heat as well as by salt, and all toxin molecules are released from DNA which remains double-stranded. Aflatoxin can bind to thermally denatured DNA as well, with an accompanying spectral shift which depends on the particular preparation of denatured DNA, and there was an isosbestic point at 380 nm. The complex of toxin and denatured DNA was stabilized by salt up to 0.1 M. Thus it was concluded that aflatoxin was bound with denatured DNA in a different form from native DNA. The number of binding sites of DNA was estimated by constructing Scatchard plots based on both spectral analysis and equilibrium dialysis. However, these show no definite value but fall in the region of 0.07 to 0.013, that is one toxin molecule per 80-140 nucleotide of native DNA. Several lines of evidence suggest the possibility that aflatoxin exists in aqueous solution as aggregates. The mechanism of the binding was discussed. It is noteworthy that the number of binding sites of DNA doubles by the presence of histones.", "contents": "Interaction of aflatoxin B1 with DNA. The interaction of aflatoxin B1 with DNA was investigated. In the presence of native DNA the absorption spectrum of the toxin showed an obvious spectral shift in the region of 300-420 nm with an isosbestic point at 376 nm. DNA-bound aflatoxin is hydrolyzed in alkaline media more easily than the free toxin. The hydrolized form has a labile structure and can decompose further. The bound toxins are easily dissociated by heat as well as by salt, and all toxin molecules are released from DNA which remains double-stranded. Aflatoxin can bind to thermally denatured DNA as well, with an accompanying spectral shift which depends on the particular preparation of denatured DNA, and there was an isosbestic point at 380 nm. The complex of toxin and denatured DNA was stabilized by salt up to 0.1 M. Thus it was concluded that aflatoxin was bound with denatured DNA in a different form from native DNA. The number of binding sites of DNA was estimated by constructing Scatchard plots based on both spectral analysis and equilibrium dialysis. However, these show no definite value but fall in the region of 0.07 to 0.013, that is one toxin molecule per 80-140 nucleotide of native DNA. Several lines of evidence suggest the possibility that aflatoxin exists in aqueous solution as aggregates. The mechanism of the binding was discussed. It is noteworthy that the number of binding sites of DNA doubles by the presence of histones."}
{"id": "PMID:236997", "title": "Studies of glucose metabolism in Bacillus subtilis. I. Purification of glucose-6-phosphate dehydrogenase from the vegetative cell and its properties in comparison with the spore enzyme.", "content": "1. Glucose-6-phosphate dehydrogenase [D-glucose-6-phosphate : NADP-+ 1-oxidoreductase, EC 1.1.1.49] from vegetative cells of Bacillus subtilis was purified about 2,400-fold. The purified enzyme was shown to be homogeneous as judged by chromatographic profile, polyacrylamide gel electrophoresis and ultracentrifugation. The correspondent enzyme from spores was also partially purified. 2. The molecular weight of the vegetative cell enzyme was estimated to be 350,000 by Sepharose 6B chromatography and sedimentation equilibrium studies, and that of its subunit was 58,000 as determined by SDS gel electrophoresis, indicating that the enzyme was found to be 240,000. 3. The vegetative cell enzyme and spore enzyme have the same Km values and pH optima. The optimum pH was about 9.2 for both enzymes and the Km values for NADP-+ and glucose-6-phosphate were determined to be 6.7 X 10-minus 6 and 7.5 X 10-minus 5M, respectively. 4. The amino acid composition of the vegetative cell enzyme was examined and was compared with those of enzymes from other sources.", "contents": "Studies of glucose metabolism in Bacillus subtilis. I. Purification of glucose-6-phosphate dehydrogenase from the vegetative cell and its properties in comparison with the spore enzyme. 1. Glucose-6-phosphate dehydrogenase [D-glucose-6-phosphate : NADP-+ 1-oxidoreductase, EC 1.1.1.49] from vegetative cells of Bacillus subtilis was purified about 2,400-fold. The purified enzyme was shown to be homogeneous as judged by chromatographic profile, polyacrylamide gel electrophoresis and ultracentrifugation. The correspondent enzyme from spores was also partially purified. 2. The molecular weight of the vegetative cell enzyme was estimated to be 350,000 by Sepharose 6B chromatography and sedimentation equilibrium studies, and that of its subunit was 58,000 as determined by SDS gel electrophoresis, indicating that the enzyme was found to be 240,000. 3. The vegetative cell enzyme and spore enzyme have the same Km values and pH optima. The optimum pH was about 9.2 for both enzymes and the Km values for NADP-+ and glucose-6-phosphate were determined to be 6.7 X 10-minus 6 and 7.5 X 10-minus 5M, respectively. 4. The amino acid composition of the vegetative cell enzyme was examined and was compared with those of enzymes from other sources."}
{"id": "PMID:236999", "title": "Purification and properties of beta-galactosidase from Aspergillus oryzae.", "content": "Beta-Galactosidase [EC 3.2.1.23] has been purified from a culture of Aspergillus oryzae by 2-propanol fractionation, column chromatography on DEAE-Sephadex A-50 and Sephadex G-200. The preparation was homogeneous on ultracentrifugation and disc electrophoresis. The enzyme showed pH optima of 4.5 with ONPG-1 as a substrate and 4.8 with lactose as a substrate. The stable pH range was from 4.0 to 9.0 and the optimum temperature was 46 degrees. The Michaelis constants were 7.2 X 10-minus 4 M with ONPG and 1.8 X 10-minus 2 M with lactose. Hg-2+, Cu-2+, N-bromosuccinimide, and sodium laurylsulfate caused marked inhibition. The apparent molecular weight was calculated to be about 105,000 by Sephadex gel filtration and sucrose density gradient centrifugation.", "contents": "Purification and properties of beta-galactosidase from Aspergillus oryzae. Beta-Galactosidase [EC 3.2.1.23] has been purified from a culture of Aspergillus oryzae by 2-propanol fractionation, column chromatography on DEAE-Sephadex A-50 and Sephadex G-200. The preparation was homogeneous on ultracentrifugation and disc electrophoresis. The enzyme showed pH optima of 4.5 with ONPG-1 as a substrate and 4.8 with lactose as a substrate. The stable pH range was from 4.0 to 9.0 and the optimum temperature was 46 degrees. The Michaelis constants were 7.2 X 10-minus 4 M with ONPG and 1.8 X 10-minus 2 M with lactose. Hg-2+, Cu-2+, N-bromosuccinimide, and sodium laurylsulfate caused marked inhibition. The apparent molecular weight was calculated to be about 105,000 by Sephadex gel filtration and sucrose density gradient centrifugation."}
{"id": "PMID:237000", "title": "Solubilization of valine-sensitive acetohydroxy acid synthetase from Neurospora mitochondria.", "content": "Acetohydroxy acid synthetase [EC 4.1.3.18] of Neurospora crassa has been solubilized from a mitochondrial pellet fraction by sonic treatment in 1.0 M potassium phosphate buffer at pH 7.5 containing 10 mM MgSO4 and centrifugation at 180,000 X g for 20 min. The soluble enzyme thus obtained has a high specific activity and a high sensitivity to valine comparable to the original mitochondrial pellet suspension when the activity was determined in high concentrations of potassium phosphate.", "contents": "Solubilization of valine-sensitive acetohydroxy acid synthetase from Neurospora mitochondria. Acetohydroxy acid synthetase [EC 4.1.3.18] of Neurospora crassa has been solubilized from a mitochondrial pellet fraction by sonic treatment in 1.0 M potassium phosphate buffer at pH 7.5 containing 10 mM MgSO4 and centrifugation at 180,000 X g for 20 min. The soluble enzyme thus obtained has a high specific activity and a high sensitivity to valine comparable to the original mitochondrial pellet suspension when the activity was determined in high concentrations of potassium phosphate."}
{"id": "PMID:237002", "title": "Enzymatic studies on a cellulase system of Trichoderma viride. II. Purification and Properties of two cellulases.", "content": "Two cellulase [EC 3.2.1.4] components derived from Meicelase, a commercial crude cellulase preparation from Trichoderma viride, were purified by consecutive column chromatography, and were designated as cellulase II-A and cellulase II-B. Cellulases II-A and II-B were each homogeneous on polyacrylamide gel electrophoresis. The molecular weights of cellulases II-A and II-B were 30,000 and 43,000, respectively, on the basis of Sephadex G-100 gel filtration. Both enzymes contained 12-14% carbohydrates (as glucose). Some properties of the purified cellulases were investigated. The optimum pH and temperature for cellulases II-A and II-B were pH 4.5-5.0 and 60 degrees, and pH 4.5-5.0 and 50 degrees, respectively. Both enzymes were stable over the range of pH 5.0-7.0 at 4 degrees for 24 hr. Cellulases II-A and II-B retained 27 and 41% of the original CM-cellulose-saccharifying activities, respectively, after heating at 100 degrees for 10 min. Both enzymes were completely inhibited by some metal ions such as 1 mM Hg-2+, and partially by 1 mM Ag-+ and Cu-2+. However, Mg-2+, Fe-2+, and several other metal ions showed no inhibition at this concentration. The hydrolysis of CM-cellulose by cellulase II-A was more random than that by cellulase II-B.", "contents": "Enzymatic studies on a cellulase system of Trichoderma viride. II. Purification and Properties of two cellulases. Two cellulase [EC 3.2.1.4] components derived from Meicelase, a commercial crude cellulase preparation from Trichoderma viride, were purified by consecutive column chromatography, and were designated as cellulase II-A and cellulase II-B. Cellulases II-A and II-B were each homogeneous on polyacrylamide gel electrophoresis. The molecular weights of cellulases II-A and II-B were 30,000 and 43,000, respectively, on the basis of Sephadex G-100 gel filtration. Both enzymes contained 12-14% carbohydrates (as glucose). Some properties of the purified cellulases were investigated. The optimum pH and temperature for cellulases II-A and II-B were pH 4.5-5.0 and 60 degrees, and pH 4.5-5.0 and 50 degrees, respectively. Both enzymes were stable over the range of pH 5.0-7.0 at 4 degrees for 24 hr. Cellulases II-A and II-B retained 27 and 41% of the original CM-cellulose-saccharifying activities, respectively, after heating at 100 degrees for 10 min. Both enzymes were completely inhibited by some metal ions such as 1 mM Hg-2+, and partially by 1 mM Ag-+ and Cu-2+. However, Mg-2+, Fe-2+, and several other metal ions showed no inhibition at this concentration. The hydrolysis of CM-cellulose by cellulase II-A was more random than that by cellulase II-B."}
{"id": "PMID:237003", "title": "Reassembly of functionally active 50S ribosomal particles from proteins and RNAs of Escherichia coli. Dependency of 50S ribosomal reassembly on 30S subunits.", "content": "Further studies were made on the reassembly of 50S ribosomal subunits from proteins and RNAs of E. coli. The reassembled particles had high activity in poly U-directed polyphenylalanine synthesis and their sucrose sedimentation properties were similar to those of the original intact particles. Several factors affecting the reassembly were examined. The optimal pH for solubilization of ribosomal proteins was pH 9.5, and the optimal Tris concentration was 0.75 to 1.00 M. In the reassembly mixture the pH was adjusted to 8.2 A sharp optimum magnesium ion concentration of 6 to 10 mM was observed. The reassembly required 0.2 to 0.5 M KCl, the optimum concentration being 0.40 M. On incubation for 20 min a temperature of 34 and 40 degrees was necessary, 37 degrees being best. Oligonucleotides, which we previously added to the reassembly mixture were found not to be necessary for inhibition of RNase II [EC 3.1.4.20] activity remaining in the reaction was found necessary to dialyze the reassembly mixture against a buffer containing 10 mM magnesium ion after the incubation. Simultaneous reassembly of 30 and 50S subunits with time was observed, showing that 70S ribosomes were formed first and that they then dissociated into subunits. Reassembly of 50S subunits from their component proteins and RNAs was completely dependent on either 30S particles or the simultaneous reassembly of 30S subunits. Other critical factors affecting the reassembly of 50S subunits must be examined, since the reproducibility of this reassembly is only about 60%, even under the above controlled conditions.", "contents": "Reassembly of functionally active 50S ribosomal particles from proteins and RNAs of Escherichia coli. Dependency of 50S ribosomal reassembly on 30S subunits. Further studies were made on the reassembly of 50S ribosomal subunits from proteins and RNAs of E. coli. The reassembled particles had high activity in poly U-directed polyphenylalanine synthesis and their sucrose sedimentation properties were similar to those of the original intact particles. Several factors affecting the reassembly were examined. The optimal pH for solubilization of ribosomal proteins was pH 9.5, and the optimal Tris concentration was 0.75 to 1.00 M. In the reassembly mixture the pH was adjusted to 8.2 A sharp optimum magnesium ion concentration of 6 to 10 mM was observed. The reassembly required 0.2 to 0.5 M KCl, the optimum concentration being 0.40 M. On incubation for 20 min a temperature of 34 and 40 degrees was necessary, 37 degrees being best. Oligonucleotides, which we previously added to the reassembly mixture were found not to be necessary for inhibition of RNase II [EC 3.1.4.20] activity remaining in the reaction was found necessary to dialyze the reassembly mixture against a buffer containing 10 mM magnesium ion after the incubation. Simultaneous reassembly of 30 and 50S subunits with time was observed, showing that 70S ribosomes were formed first and that they then dissociated into subunits. Reassembly of 50S subunits from their component proteins and RNAs was completely dependent on either 30S particles or the simultaneous reassembly of 30S subunits. Other critical factors affecting the reassembly of 50S subunits must be examined, since the reproducibility of this reassembly is only about 60%, even under the above controlled conditions."}
{"id": "PMID:237004", "title": "Kinetic studies of carboxypeptidase Y. I. Kinetic parameters for the hydrolysis of synthetic substrates.", "content": "Kinetic parameters for carboxypeptidase Y [EC 3.4.12.1], characterized as a nonspecific enzyme, are given for the hydrolysis of a series of acylated peptides, acylated amino acid esters, and amides. We confirmed that the enzyme released COOH-terminal proline and beta-alanine at an appreciable rate, as well as neutral amino acids with aromatic and aliphatic side chains at a very high speed. The rates of hydrolysis of ester and amide substrates were compatible with those produced by chymotrypsin [EC 3.4.21.1]. Stereospecificity was also demonstrated by the failure to hydrolyze peptide, ester, amide, and anilide substrates containing a D-amino acid. The effects of pH, solvents, and salt concentrations on the kinetic parameters of hydrolysis of peptide and ester substrates are also described.", "contents": "Kinetic studies of carboxypeptidase Y. I. Kinetic parameters for the hydrolysis of synthetic substrates. Kinetic parameters for carboxypeptidase Y [EC 3.4.12.1], characterized as a nonspecific enzyme, are given for the hydrolysis of a series of acylated peptides, acylated amino acid esters, and amides. We confirmed that the enzyme released COOH-terminal proline and beta-alanine at an appreciable rate, as well as neutral amino acids with aromatic and aliphatic side chains at a very high speed. The rates of hydrolysis of ester and amide substrates were compatible with those produced by chymotrypsin [EC 3.4.21.1]. Stereospecificity was also demonstrated by the failure to hydrolyze peptide, ester, amide, and anilide substrates containing a D-amino acid. The effects of pH, solvents, and salt concentrations on the kinetic parameters of hydrolysis of peptide and ester substrates are also described."}
{"id": "PMID:237005", "title": "Kinetic studies of carboxypeptidase Y. II.  Effects of substrate and product analogs on peptidase and esterase activities.", "content": "Reversible inhibition of the peptidase and esterase activities of CPase Y [EC 3.4.12.1] was investigated with substrate and product analogs known to be inhibitors or effectors of pancreatic carboxypeptidases A or B [EC 3.4.12.2 or 3]. L-Amino acids and NH2-blocked L-Amino acids showed competitive-type inhibition, whereas their D-enantiomers caused less inhibition than the L-enantiomers, and showed non-competitive or mixed-type inhibition. Some phenylalanine analogs, e.g. beta-phenylpropionic acid and t-cinnamic acid, were also reversible inhibitors of CPase Y. The type of these inhibitors and their K1 values were generally parallel for both the peptidase and esterase activities.", "contents": "Kinetic studies of carboxypeptidase Y. II.  Effects of substrate and product analogs on peptidase and esterase activities. Reversible inhibition of the peptidase and esterase activities of CPase Y [EC 3.4.12.1] was investigated with substrate and product analogs known to be inhibitors or effectors of pancreatic carboxypeptidases A or B [EC 3.4.12.2 or 3]. L-Amino acids and NH2-blocked L-Amino acids showed competitive-type inhibition, whereas their D-enantiomers caused less inhibition than the L-enantiomers, and showed non-competitive or mixed-type inhibition. Some phenylalanine analogs, e.g. beta-phenylpropionic acid and t-cinnamic acid, were also reversible inhibitors of CPase Y. The type of these inhibitors and their K1 values were generally parallel for both the peptidase and esterase activities."}
{"id": "PMID:237006", "title": "The distribution of anionic sites on the surfaces of mitochondrial membranes. Visual probing with polycationic ferritin.", "content": "Polycationic ferritin, a multivalent ligand, was used as a visual probe to determine the distribution and density of anionic sites on the surfaces of rat liver mitochondrial membranes. Both the distribution of bound polycationic ferritin and the topography of the outer surface of the inner mitochondrial membrane were studied in depth by utilizing thin sections and critical-point dried, whole mount preparations for transmission electron microscopy and by scanning electron microscopy. Based on its relative affinity for polycationic ferritin, the surface of the inner membrane contains discrete regions of high density and low density anionic sites. Whereas the surface of the cristal membrane contains a low density of anionic sites, the surface of the inner boundary membrane contains patches of high density anionic sites. The high density anionic sites on the inner boundary membrane were found to persist as stable patches and did not dissociate or randomize freely when the membrane was converted osmotically to a spherical configuration. The observations suggest that the inner mitochondrial membrane is composed of two major regions of anionic macromolecular distinction. It is well-known that an intermembrane space exists between the two membranes of the intact mitochondrion; however, a number of contact sites occur between the two membranes. We determined that the outer membrane, partially disrupted by treatment with digitonin, remains attached to the inner membrane at these contact sites as inverted vesicles. Such attached vesicles show that the inner surface of the outer membrane contains anionic sites, but of decreased density, surrounding the contact sites. Thus, the intermembrane space in the intact mitochondrion may be maintained by electronegative surfaces of the two mitochondrial membranes. The distribution of anionic sites on the outer surface of the outer membrane is random. The nature and function of fixed anionic surface charges and membrane contact sites are discussed with regard to recent reports relating to calcium transport, protein assembly into mitochondrial membranes, and membrane fluidity.", "contents": "The distribution of anionic sites on the surfaces of mitochondrial membranes. Visual probing with polycationic ferritin. Polycationic ferritin, a multivalent ligand, was used as a visual probe to determine the distribution and density of anionic sites on the surfaces of rat liver mitochondrial membranes. Both the distribution of bound polycationic ferritin and the topography of the outer surface of the inner mitochondrial membrane were studied in depth by utilizing thin sections and critical-point dried, whole mount preparations for transmission electron microscopy and by scanning electron microscopy. Based on its relative affinity for polycationic ferritin, the surface of the inner membrane contains discrete regions of high density and low density anionic sites. Whereas the surface of the cristal membrane contains a low density of anionic sites, the surface of the inner boundary membrane contains patches of high density anionic sites. The high density anionic sites on the inner boundary membrane were found to persist as stable patches and did not dissociate or randomize freely when the membrane was converted osmotically to a spherical configuration. The observations suggest that the inner mitochondrial membrane is composed of two major regions of anionic macromolecular distinction. It is well-known that an intermembrane space exists between the two membranes of the intact mitochondrion; however, a number of contact sites occur between the two membranes. We determined that the outer membrane, partially disrupted by treatment with digitonin, remains attached to the inner membrane at these contact sites as inverted vesicles. Such attached vesicles show that the inner surface of the outer membrane contains anionic sites, but of decreased density, surrounding the contact sites. Thus, the intermembrane space in the intact mitochondrion may be maintained by electronegative surfaces of the two mitochondrial membranes. The distribution of anionic sites on the outer surface of the outer membrane is random. The nature and function of fixed anionic surface charges and membrane contact sites are discussed with regard to recent reports relating to calcium transport, protein assembly into mitochondrial membranes, and membrane fluidity."}
{"id": "PMID:237008", "title": "Affinity chromatography of beta-galactosidase on controlled-pore glass derivatives.", "content": "Several controlled-pore glass (CPG) derivatives were examined as supports for the affinity chromatographic purification of the enzyme beta-galactosidase. The competitive inhibitor p-aminophenyl-beta-D-thiogalactopyranoside was coupled to an azelaic acid and a malonic acid derivative of 750-A alkylamine CPG of 80-120 mesh and to an azelaic acid derivative of 550-A alkylamine CPG of 40-80 mesh. The latter derivative exhibited particularly good load capacity and separation efficiency; however, both arm lengths were effective. Hydrophobic interactions between the arm and the enzyme contribute to the separation.", "contents": "Affinity chromatography of beta-galactosidase on controlled-pore glass derivatives. Several controlled-pore glass (CPG) derivatives were examined as supports for the affinity chromatographic purification of the enzyme beta-galactosidase. The competitive inhibitor p-aminophenyl-beta-D-thiogalactopyranoside was coupled to an azelaic acid and a malonic acid derivative of 750-A alkylamine CPG of 80-120 mesh and to an azelaic acid derivative of 550-A alkylamine CPG of 40-80 mesh. The latter derivative exhibited particularly good load capacity and separation efficiency; however, both arm lengths were effective. Hydrophobic interactions between the arm and the enzyme contribute to the separation."}
{"id": "PMID:237009", "title": "Separation of pyrimidine deoxyribooligonucleotides according to length and composition using thin-layer chromatography on deae-cellulose.", "content": "A procedure has been developed for the fractionation of pyrimidine deoxyribo-oligonucleotides, PynPn+1, according to length and composition using ascending thin-layer chromatography on DEAE-cellulose. The separation of oligonucleotides according to length (n=1-7) into individual isopliths was carried out using a linear 0-0.35 M sodium chloride gradient in 0.01 M sodium acetate buffer of pH 5.1-5.3 and 5 M urea. Then the oligonucleotides of individual isopliths were separated according to composition using the same gradient of sodium chloride in 0.01 M sodium acetate or sodium citrate buffer of pH 3.2. The procedure can be used for rapid fractionation (2-3 h) and serial determination of the frequencies of pyrimidine sequences differing in length and composition in DNAs of various origin. The procedure can be used for both preparative and analytical applications. It was employed to study the distribution of 5-methylcytosine in pyrimidine isopliths of some DNAs.", "contents": "Separation of pyrimidine deoxyribooligonucleotides according to length and composition using thin-layer chromatography on deae-cellulose. A procedure has been developed for the fractionation of pyrimidine deoxyribo-oligonucleotides, PynPn+1, according to length and composition using ascending thin-layer chromatography on DEAE-cellulose. The separation of oligonucleotides according to length (n=1-7) into individual isopliths was carried out using a linear 0-0.35 M sodium chloride gradient in 0.01 M sodium acetate buffer of pH 5.1-5.3 and 5 M urea. Then the oligonucleotides of individual isopliths were separated according to composition using the same gradient of sodium chloride in 0.01 M sodium acetate or sodium citrate buffer of pH 3.2. The procedure can be used for rapid fractionation (2-3 h) and serial determination of the frequencies of pyrimidine sequences differing in length and composition in DNAs of various origin. The procedure can be used for both preparative and analytical applications. It was employed to study the distribution of 5-methylcytosine in pyrimidine isopliths of some DNAs."}
{"id": "PMID:237010", "title": "Relationship between densitometric peak area and concentration of lipid in the quantitative analysis of a lipid mixture separated by thin-layer chromatography.", "content": "A mixture of the neutral lipids squalene, cetyl stearate, triolein, oleic acid and cholesterol was separated by thin-layer chromatography and the components were measured quantitatively by photodensitometry. Several empirical expressions relating densitometric peak area (A) and lipid concentration (C) were subjected to statistical analysis, and the relationship A=k-C-B is linear in the logarithmic form log A=B-log c -0g k within 95% confidence limits on the observed results. Exponent B, representing the proportionality factor in the expression relating the relative differential changes in peak area and concentration, is constant for lipids studied on the same chromatoplate, whereas the constant k is lipid dependent. All standard measurements per plate are therefore utilized for estimating a common B value, which gives greater accuracy than in the individual cases. The plate capacity for measurements of unknown lipid concentrations may consequently be increased, as a common B value, based on a reduced number of standard measurements, may be estimated with the same accuracy as an individual B value, based upon the non-reduced number of standard measurements. Equations are given for the calculation of B and k and for the determination of unknown concentrations with appropriate confidence intervals.", "contents": "Relationship between densitometric peak area and concentration of lipid in the quantitative analysis of a lipid mixture separated by thin-layer chromatography. A mixture of the neutral lipids squalene, cetyl stearate, triolein, oleic acid and cholesterol was separated by thin-layer chromatography and the components were measured quantitatively by photodensitometry. Several empirical expressions relating densitometric peak area (A) and lipid concentration (C) were subjected to statistical analysis, and the relationship A=k-C-B is linear in the logarithmic form log A=B-log c -0g k within 95% confidence limits on the observed results. Exponent B, representing the proportionality factor in the expression relating the relative differential changes in peak area and concentration, is constant for lipids studied on the same chromatoplate, whereas the constant k is lipid dependent. All standard measurements per plate are therefore utilized for estimating a common B value, which gives greater accuracy than in the individual cases. The plate capacity for measurements of unknown lipid concentrations may consequently be increased, as a common B value, based on a reduced number of standard measurements, may be estimated with the same accuracy as an individual B value, based upon the non-reduced number of standard measurements. Equations are given for the calculation of B and k and for the determination of unknown concentrations with appropriate confidence intervals."}
{"id": "PMID:237012", "title": "Separation of dehydrogenases on polyaminomethylstyrene.", "content": "The binding of dehydrogenases, especially alcohol dehydrogenase, and other proteins to several ion exchangers and hydrophobic polymers was investigated. Quantitative parameters for the stability of the polymer-protein complexes (obtained form double reciprocal plots) indicate a high but different affinity of many proteins for polyaminomethylstyrene. The chromatography of a mixture of five dehydrogenases and human serum albumin on polyaminomethylstyrene is described.", "contents": "Separation of dehydrogenases on polyaminomethylstyrene. The binding of dehydrogenases, especially alcohol dehydrogenase, and other proteins to several ion exchangers and hydrophobic polymers was investigated. Quantitative parameters for the stability of the polymer-protein complexes (obtained form double reciprocal plots) indicate a high but different affinity of many proteins for polyaminomethylstyrene. The chromatography of a mixture of five dehydrogenases and human serum albumin on polyaminomethylstyrene is described."}
{"id": "PMID:237013", "title": "Gas chromatographic-mass spectrometric determination of intact C3-hydroxylated benzodiazepine glucoronides in urine.", "content": "A method is described for the determination C3-hydroxylated benzodiazepine glucuronides in biological samples. Oxazepam and lorazepam glucuronides are measured as methyl esters and trimethylsilyl derivates by a gas chromatographic procedure. The applicability of the method has been tested on the urine of rats, guinea pigs, rabbits and man, receiving oxazepam orally. Oxazepam glucuronide was not found in rat urine but it was present in the urine of rabbits (5.7% of the administered dose), guinea pigs (9.5%) and man (13.4-26.9%).", "contents": "Gas chromatographic-mass spectrometric determination of intact C3-hydroxylated benzodiazepine glucoronides in urine. A method is described for the determination C3-hydroxylated benzodiazepine glucuronides in biological samples. Oxazepam and lorazepam glucuronides are measured as methyl esters and trimethylsilyl derivates by a gas chromatographic procedure. The applicability of the method has been tested on the urine of rats, guinea pigs, rabbits and man, receiving oxazepam orally. Oxazepam glucuronide was not found in rat urine but it was present in the urine of rabbits (5.7% of the administered dose), guinea pigs (9.5%) and man (13.4-26.9%)."}
{"id": "PMID:237014", "title": "Progesterone receptor of the human myometrium.", "content": "A progesterone binding protein was characterized in the cytosol of human myometrium. The receptor sedimented in the 4S region on sucrose gradients and had an equilibrium dissociation constant of 3.7 times 10-9M. Synthetic progestagens had an affinity equivalent to that of progesterone while cortisol had low affinity for the binding protein. These same progestagens showed very low binding to human CBG. In normally cycling women, the total levels of cytosol receptor were higher during the follicular phase than during the luteal phase. Subjects taking oral contraceptives and those who were pregnant had the lowest concentration of myometrial progesterone receptor. Postmenopausal women had levels of myometrial receptor lower than those of the secretory phase of the cycle. Estrogen therapy increased the receptor concentrations of the menopausal myometrium to those of the proliferative phase. The estradiol receptor levels of myometrial cytosol revealed similar changes in cycling women. When both binding proteins were measured concurrently in the same specimen, there was a significant positive correlation.", "contents": "Progesterone receptor of the human myometrium. A progesterone binding protein was characterized in the cytosol of human myometrium. The receptor sedimented in the 4S region on sucrose gradients and had an equilibrium dissociation constant of 3.7 times 10-9M. Synthetic progestagens had an affinity equivalent to that of progesterone while cortisol had low affinity for the binding protein. These same progestagens showed very low binding to human CBG. In normally cycling women, the total levels of cytosol receptor were higher during the follicular phase than during the luteal phase. Subjects taking oral contraceptives and those who were pregnant had the lowest concentration of myometrial progesterone receptor. Postmenopausal women had levels of myometrial receptor lower than those of the secretory phase of the cycle. Estrogen therapy increased the receptor concentrations of the menopausal myometrium to those of the proliferative phase. The estradiol receptor levels of myometrial cytosol revealed similar changes in cycling women. When both binding proteins were measured concurrently in the same specimen, there was a significant positive correlation."}
{"id": "PMID:237015", "title": "Biochemical properties of big renin extracted from human plasma.", "content": "The properties of big renin, a relatively inactive form of renin isolated from human plasma, were examined following partial purification by gel filtration. Exposure of big renin to pH 3.0-3.6, or brief incubation with trypsin or pepsin, resulted in a ten-fold increase in enzymatic activity. Activation was not effected by 4M NaCl, 6M urea, or incubation with neuraminidase. Both before and after inactivation, big renin eluted from Sephadex gel more rapidly than normal plasma renin. During polyacrylamide gel disc electrophoresis, inactive big renin migrated more slowly than either normal renin or big renin previously activated. Using sheep substrate, the enzyme kinetics of normal renin and previously activated big renin were identical, while inactive big renin possessed a higher Michaelis constant. These data indicate that big renin is closely related biochemically to normal plasma renin. As the activation of big renin results in the formation of the substance even more similar to normal renin, the possibility exists that big renin may prove to be a precursor form of normal renin.", "contents": "Biochemical properties of big renin extracted from human plasma. The properties of big renin, a relatively inactive form of renin isolated from human plasma, were examined following partial purification by gel filtration. Exposure of big renin to pH 3.0-3.6, or brief incubation with trypsin or pepsin, resulted in a ten-fold increase in enzymatic activity. Activation was not effected by 4M NaCl, 6M urea, or incubation with neuraminidase. Both before and after inactivation, big renin eluted from Sephadex gel more rapidly than normal plasma renin. During polyacrylamide gel disc electrophoresis, inactive big renin migrated more slowly than either normal renin or big renin previously activated. Using sheep substrate, the enzyme kinetics of normal renin and previously activated big renin were identical, while inactive big renin possessed a higher Michaelis constant. These data indicate that big renin is closely related biochemically to normal plasma renin. As the activation of big renin results in the formation of the substance even more similar to normal renin, the possibility exists that big renin may prove to be a precursor form of normal renin."}
{"id": "PMID:237016", "title": "Plasma LH and FSH response to LRH in boys with compensatory testicular hypertrophy.", "content": "The plasma LH, FSH and testosterone response to LRH was studied in 12 boys with compensatory testicular hypertrophy (CTH) and normal puberty and in a matched control group with normal testicular development. It was found, that the boys with CTH had normal basal plasma testosterone and LH concentrations; at the same time the basal plasma FSH level were significantly higher than in the control group. The response of plasma LH and FSH to LRH was markedly greater in the CTH group than it was in the control group. It is concluded, that the contralateral testicular hypertrophy which enables a normal pubertal process is the result of increased secretion of gonadotropins, mainly FSH.", "contents": "Plasma LH and FSH response to LRH in boys with compensatory testicular hypertrophy. The plasma LH, FSH and testosterone response to LRH was studied in 12 boys with compensatory testicular hypertrophy (CTH) and normal puberty and in a matched control group with normal testicular development. It was found, that the boys with CTH had normal basal plasma testosterone and LH concentrations; at the same time the basal plasma FSH level were significantly higher than in the control group. The response of plasma LH and FSH to LRH was markedly greater in the CTH group than it was in the control group. It is concluded, that the contralateral testicular hypertrophy which enables a normal pubertal process is the result of increased secretion of gonadotropins, mainly FSH."}
{"id": "PMID:237017", "title": "Diazepam and meperidine on arterial blood gases in patients with chronic obstructive pulmonary disease.", "content": "Arterial blood gases were not significantly altered by 0.15 mg/kg intravenous dose of diazepam in patients with chronic obstructive lung disease. The PalphaO-2 was significantly reduced and the P-alphaCO-2 increased after administration of 1.5 mg/kg meperidine intravenously and the combination of 1.5 mg/kg meperidine with 0.15 mg/kg diazepam. Diazepam did not, however, significantly increase the ventilatory depression induced by meperidine. Therefore, 0.15 mg/kg diazepam intravenously causes no ventilatory depression by meperidine in patients with chronic obstructive lung diseases.", "contents": "Diazepam and meperidine on arterial blood gases in patients with chronic obstructive pulmonary disease. Arterial blood gases were not significantly altered by 0.15 mg/kg intravenous dose of diazepam in patients with chronic obstructive lung disease. The PalphaO-2 was significantly reduced and the P-alphaCO-2 increased after administration of 1.5 mg/kg meperidine intravenously and the combination of 1.5 mg/kg meperidine with 0.15 mg/kg diazepam. Diazepam did not, however, significantly increase the ventilatory depression induced by meperidine. Therefore, 0.15 mg/kg diazepam intravenously causes no ventilatory depression by meperidine in patients with chronic obstructive lung diseases."}
{"id": "PMID:237035", "title": "Capillary pH and blood gas determinations in asthmatic children.", "content": "Earlobe capillary pH and blood gases in asthmatic children were compared to arterial values. Hyperemia of the earlobe was produced by applying thurfyl nicotinate (Trafuril). Approximately 15 min later capillary blood was obtained simultaneously with a radial arterial sample. Earlobe capillary PO2, PO2, and pH correlated well with arterial values. This technique is simple, safe, and appears to be a satisfactory substitute for arterial blood in normotensive asthmatic children.", "contents": "Capillary pH and blood gas determinations in asthmatic children. Earlobe capillary pH and blood gases in asthmatic children were compared to arterial values. Hyperemia of the earlobe was produced by applying thurfyl nicotinate (Trafuril). Approximately 15 min later capillary blood was obtained simultaneously with a radial arterial sample. Earlobe capillary PO2, PO2, and pH correlated well with arterial values. This technique is simple, safe, and appears to be a satisfactory substitute for arterial blood in normotensive asthmatic children."}
{"id": "PMID:237053", "title": "A new colimetric assay for monoamine oxidase in serum and its clinical application.", "content": "A new colimetric assay for serum monoamine oxidase and clinical findings based on this method are described. This rapid, precise procedure employs 1-[(4-aminomethylphenyl)azol]-2-naphthol as a substrate. The enzymatically generated 1-[(4-formyl phenyl)azo]-2-naphthol is extracted into cyclohexane to form a colored solution whose absorbance is determined at 500 nm. The method proved to be extremely simple, and the results obtained correlated well with those given by the standard method of McEwen.", "contents": "A new colimetric assay for monoamine oxidase in serum and its clinical application. A new colimetric assay for serum monoamine oxidase and clinical findings based on this method are described. This rapid, precise procedure employs 1-[(4-aminomethylphenyl)azol]-2-naphthol as a substrate. The enzymatically generated 1-[(4-formyl phenyl)azo]-2-naphthol is extracted into cyclohexane to form a colored solution whose absorbance is determined at 500 nm. The method proved to be extremely simple, and the results obtained correlated well with those given by the standard method of McEwen."}
{"id": "PMID:237054", "title": "Effect of hemodialysis on factors influencing oxygen transport.", "content": "Ten patients underwent 4 study hemodialyses, one with standard dialysis conditions, one with an isophosphate dialysate, one with simultaneous ammonium chloride loading, and other, after pretreatment, with sodium bicarbonate. Measurement of hemoglobin oxygen affinity (P-50), erythrocyte 2,3-DPG, blood-gasses, and serum chemistries revealed biochemically effective hemodialyses and slight changes in oxygen transport parameters. The P-50 (in vivo) values decreased slightly but significantly (p greater than 0.05) with dialysis. When corrected to pH 7.4, eliminating the Bohr effect, P-50 increased (p greater than 0.05). With unmodified dialysis elevated values of 2,3-DPG (in comparison to normal) decreased, a change that did not correlate with delta-p-50, delta-serum phosphate, or delta-serum creatinine. With standard and isophosphate dialyses Po-2 decreased significantly. The decrease correlated with delta-hydrogen ion concentration and did not occur with dialyses designed to maintain pH constant. Thus, hemodialysis influences many factors that affect oxygen transport in different and counterbalancing directions. These changes are not totally explained by alterations in 2,3-DPG, pH or serum phosphate. Maintenance of acidosis or hyperphosphatemia during dialysis is not recommended.", "contents": "Effect of hemodialysis on factors influencing oxygen transport. Ten patients underwent 4 study hemodialyses, one with standard dialysis conditions, one with an isophosphate dialysate, one with simultaneous ammonium chloride loading, and other, after pretreatment, with sodium bicarbonate. Measurement of hemoglobin oxygen affinity (P-50), erythrocyte 2,3-DPG, blood-gasses, and serum chemistries revealed biochemically effective hemodialyses and slight changes in oxygen transport parameters. The P-50 (in vivo) values decreased slightly but significantly (p greater than 0.05) with dialysis. When corrected to pH 7.4, eliminating the Bohr effect, P-50 increased (p greater than 0.05). With unmodified dialysis elevated values of 2,3-DPG (in comparison to normal) decreased, a change that did not correlate with delta-p-50, delta-serum phosphate, or delta-serum creatinine. With standard and isophosphate dialyses Po-2 decreased significantly. The decrease correlated with delta-hydrogen ion concentration and did not occur with dialyses designed to maintain pH constant. Thus, hemodialysis influences many factors that affect oxygen transport in different and counterbalancing directions. These changes are not totally explained by alterations in 2,3-DPG, pH or serum phosphate. Maintenance of acidosis or hyperphosphatemia during dialysis is not recommended."}
{"id": "PMID:237058", "title": "Alkaline phosphatase isozymes of Xenopus laevis embryos and tissues.", "content": "Alkaline phosphatase was obtained by treating embryos of Xenopus laevis with n-butanol at different developmental stages from gastrula to tadpole; the enzyme was also obtained from adult kidney, liver, and intestinal mucosa. Purification was carried out by gel filtration and polyacrylamide gel electrophoresis. The enzyme activity is chromatographically spearated into two peaks, with molecular weights of approximately 200,000 and 400,000. Alternatively, two groups may be characterized on the basis of their electrophoretic mobilities, which correspond to the different molecular weight classes. Effects of pH, temperature, inhibitors, and substrate concentration were studied. The kinetic and physical properties of the two alkaline phosphatase isozymes are similar, and are comparable to the properties reported for this enzyme from other vertebrates. Alkaline phosphatase activity increased sharply at the gastrula stage and reached a plateau at the late tailbud stage. During this period there was an 18-fold increase in activity.", "contents": "Alkaline phosphatase isozymes of Xenopus laevis embryos and tissues. Alkaline phosphatase was obtained by treating embryos of Xenopus laevis with n-butanol at different developmental stages from gastrula to tadpole; the enzyme was also obtained from adult kidney, liver, and intestinal mucosa. Purification was carried out by gel filtration and polyacrylamide gel electrophoresis. The enzyme activity is chromatographically spearated into two peaks, with molecular weights of approximately 200,000 and 400,000. Alternatively, two groups may be characterized on the basis of their electrophoretic mobilities, which correspond to the different molecular weight classes. Effects of pH, temperature, inhibitors, and substrate concentration were studied. The kinetic and physical properties of the two alkaline phosphatase isozymes are similar, and are comparable to the properties reported for this enzyme from other vertebrates. Alkaline phosphatase activity increased sharply at the gastrula stage and reached a plateau at the late tailbud stage. During this period there was an 18-fold increase in activity."}
{"id": "PMID:237059", "title": "Composition of fluid from the notochordal canal of the coelacanth, Latimeria chalumnae.", "content": "Fluid from the notochordal canal of the coelacanth, Latimeria chalumnae, was analyzed for major inorganic and organic constituents and compared with blood serum from the same fish. Significantly or suggestively lower levels of sodium, magnesium, calcium, bicarbonate, sulfate, total carbohydrates, glucose, lactate, cholesterol, bound phosphate and total proteins were found in notochordal fluid than in serum, whereas potassium, chloride, urea, trimethylamine oxide, and total free amino acids were higher and inorganic phosphorus essentially identical. Osmolarity of notochordal fluid (1058 mOsm) exceeds that of serum (942 mOsm). A whitish precipitate in the fluid consisted of a matrix of fibers 100 A in diameter and of indefinite length. It resembled a sialoglycoprotein in composition and was stabilized by disulfide bonds. The fluid contained cellular debris.", "contents": "Composition of fluid from the notochordal canal of the coelacanth, Latimeria chalumnae. Fluid from the notochordal canal of the coelacanth, Latimeria chalumnae, was analyzed for major inorganic and organic constituents and compared with blood serum from the same fish. Significantly or suggestively lower levels of sodium, magnesium, calcium, bicarbonate, sulfate, total carbohydrates, glucose, lactate, cholesterol, bound phosphate and total proteins were found in notochordal fluid than in serum, whereas potassium, chloride, urea, trimethylamine oxide, and total free amino acids were higher and inorganic phosphorus essentially identical. Osmolarity of notochordal fluid (1058 mOsm) exceeds that of serum (942 mOsm). A whitish precipitate in the fluid consisted of a matrix of fibers 100 A in diameter and of indefinite length. It resembled a sialoglycoprotein in composition and was stabilized by disulfide bonds. The fluid contained cellular debris."}
{"id": "PMID:237067", "title": "Effects of diets containing dried whey on the lactase activity of the small intestinal mucosa and the contents of the small intestine and cecum of the pig.", "content": "Two studies were conducted to establish the effects of dietary lactose supplied from dried whey on the lactase activity in the contents of the small intestine and cecum as well as the mucosa of the small intestine. In the first study, feeding 0, 10, 25, or 40% dried whey for 120 days did not alter the mucosal lactase specific activity (mumoles galactose released/mg protein) in the duodenum, upper jejunum, or lower ileum. In the second study, total lactase activity in the small intestine was estimated from the total activity found in 10-cm segments of each meter of small intestine. Feeding a diet containing 40% whey continuously from weaning at 5 weeks of age or from 12 weeks of age did not alter the total lactase activity of pigs killed at 21 weeks of age. Dietary lactose tended to increase the lactase activity in the contents of the cecum and small intestine, but the increases were not always statistically significant. In the second study, Chester White pigs had approximately threefold greater mucosal lactase activities than that of Hampshires. These two breeds may be suitable models for detailed studies into the relationships between lactase deficiency and lactose intolerance.", "contents": "Effects of diets containing dried whey on the lactase activity of the small intestinal mucosa and the contents of the small intestine and cecum of the pig. Two studies were conducted to establish the effects of dietary lactose supplied from dried whey on the lactase activity in the contents of the small intestine and cecum as well as the mucosa of the small intestine. In the first study, feeding 0, 10, 25, or 40% dried whey for 120 days did not alter the mucosal lactase specific activity (mumoles galactose released/mg protein) in the duodenum, upper jejunum, or lower ileum. In the second study, total lactase activity in the small intestine was estimated from the total activity found in 10-cm segments of each meter of small intestine. Feeding a diet containing 40% whey continuously from weaning at 5 weeks of age or from 12 weeks of age did not alter the total lactase activity of pigs killed at 21 weeks of age. Dietary lactose tended to increase the lactase activity in the contents of the cecum and small intestine, but the increases were not always statistically significant. In the second study, Chester White pigs had approximately threefold greater mucosal lactase activities than that of Hampshires. These two breeds may be suitable models for detailed studies into the relationships between lactase deficiency and lactose intolerance."}
{"id": "PMID:237069", "title": "Effects of a human plasma fraction on leucocyte migration into inflammatory exudates.", "content": "A fraction prepared from normal human plasma inhibits the migration of polymorphonuclear and mononuclear leucocytes into inflammatory exudates produced by the intrapleural injection of carrageeman or turpentine by the subcutaneous implantation of polyvinyl sponges in the rat. The mechanism of the effect does not involve complement depletion.", "contents": "Effects of a human plasma fraction on leucocyte migration into inflammatory exudates. A fraction prepared from normal human plasma inhibits the migration of polymorphonuclear and mononuclear leucocytes into inflammatory exudates produced by the intrapleural injection of carrageeman or turpentine by the subcutaneous implantation of polyvinyl sponges in the rat. The mechanism of the effect does not involve complement depletion."}
{"id": "PMID:237070", "title": "Effect of pregnenolone-16alpha-carbonitrile (PCN) on drug response in man.", "content": "Pregnenolone-16alpha-carbonitrile (PCN), which alters drug responses and induces hepatic microsomal drugs-metabolizing enzymes in experimental animals, is well-tolerated in man. There were no marked changes in the concentrations of blood sugar and urea; marked changes in the concentrations of blood sugar and urea; bromsulphophthalein (BSP) clearance; serum alkaline phosphatase activity; hematocrit, erythrocyte and leukocyte counts; as well as in ecg patterns. When the steroid was given by mouth for 4 days to patients treated with electroshock for psychiatric disorders, it decreased suxamethonium-induced skeletal muscle fasciculation and shortened thiopentone as well as propanidid anaesthesia. Breathing was resumed more rapidly than in control subjects. The protective effect of PCN is probably mediated through induction of activation or hepatic drug-metabolizing enzymes, or both.", "contents": "Effect of pregnenolone-16alpha-carbonitrile (PCN) on drug response in man. Pregnenolone-16alpha-carbonitrile (PCN), which alters drug responses and induces hepatic microsomal drugs-metabolizing enzymes in experimental animals, is well-tolerated in man. There were no marked changes in the concentrations of blood sugar and urea; marked changes in the concentrations of blood sugar and urea; bromsulphophthalein (BSP) clearance; serum alkaline phosphatase activity; hematocrit, erythrocyte and leukocyte counts; as well as in ecg patterns. When the steroid was given by mouth for 4 days to patients treated with electroshock for psychiatric disorders, it decreased suxamethonium-induced skeletal muscle fasciculation and shortened thiopentone as well as propanidid anaesthesia. Breathing was resumed more rapidly than in control subjects. The protective effect of PCN is probably mediated through induction of activation or hepatic drug-metabolizing enzymes, or both."}
{"id": "PMID:237071", "title": "The solubilization of some local anaesthetic ester of p-aminobenzoic acid by lysophosphatidylcholine.", "content": "The solubilization by lysophosphatidylcholine (LPC) of three n-alkyl esters of p-aminobenzoic acid has been studied. These esters have a local anaesthetic action. Quantitative studies show that the amount of compound solubilized is proportional to the LPC concentration and that solubilization increases in the order ethyl, n-propyl and n-butyl ester. 100MHz nmr studies indicate that the local anaesthetic esters are solubilized in the hydrocarbon interior of the LPC.", "contents": "The solubilization of some local anaesthetic ester of p-aminobenzoic acid by lysophosphatidylcholine. The solubilization by lysophosphatidylcholine (LPC) of three n-alkyl esters of p-aminobenzoic acid has been studied. These esters have a local anaesthetic action. Quantitative studies show that the amount of compound solubilized is proportional to the LPC concentration and that solubilization increases in the order ethyl, n-propyl and n-butyl ester. 100MHz nmr studies indicate that the local anaesthetic esters are solubilized in the hydrocarbon interior of the LPC."}
{"id": "PMID:237080", "title": "Narcotic agonist and antagonist potencies of a homologous series of N-alkyl-norketobemidones measured by the guinea-pig ileum and mouse vas deferens methods.", "content": "The narcotic agonist and antagonist potencies of the series of N-alkyl-norketobemidones from norketobemidone to decylnorketo-bemidone have been determined. The values obtained in the electrically stimulated preparations of the guinea-pig ileum and the mouse vas deferens are closely correlated. The agonist potencies observed in the guinea-pig ileum agree well with those found in the mouse hot-plate test (Oh-ishi & May) and those obtained by determining the inhibition of naloxone binding in brain homogenates (Wilson, Rogers, Pert & Snyder). The antagonist potencies in the guinea-pig ileum and, to a lesser extent, those in the mouse vas deferens agree with the values obtained in the morphine-dependent monkey.", "contents": "Narcotic agonist and antagonist potencies of a homologous series of N-alkyl-norketobemidones measured by the guinea-pig ileum and mouse vas deferens methods. The narcotic agonist and antagonist potencies of the series of N-alkyl-norketobemidones from norketobemidone to decylnorketo-bemidone have been determined. The values obtained in the electrically stimulated preparations of the guinea-pig ileum and the mouse vas deferens are closely correlated. The agonist potencies observed in the guinea-pig ileum agree well with those found in the mouse hot-plate test (Oh-ishi & May) and those obtained by determining the inhibition of naloxone binding in brain homogenates (Wilson, Rogers, Pert & Snyder). The antagonist potencies in the guinea-pig ileum and, to a lesser extent, those in the mouse vas deferens agree with the values obtained in the morphine-dependent monkey."}
{"id": "PMID:237081", "title": "Some effects of pilocarpine and acetylcholine on the responses of the guinea-pig vas deferens to hypogastric nerve stimulation and transmural stimulation and applied (minus)-noradrenaline.", "content": "Enhancement by acetylcholine and by pilocarpine of the contractile responses of the guinea-pig isolated vas deferens to hypogastric nerve and transmural stimulation and to exogenous (minus)-noradrenaline was examined. At high concentration (600 nM) acetylcholine enhanced responses in the order:hypogastric nerve greater than transmural greater than exogenous (minus)-noradrenaline. Pilocarpine produced a similar maximal degree of enchancement with all three stimuli. All these effects were reversibly inhibited by 1-4 mum atropine, a concentration which alone did not affected responses to the stimuli. Pilocarpine (50-400 muM) gave a concentration-related inhibition of the enhancement of responses to hypogastric nerve stimulation by 600 nM acetylcholine.", "contents": "Some effects of pilocarpine and acetylcholine on the responses of the guinea-pig vas deferens to hypogastric nerve stimulation and transmural stimulation and applied (minus)-noradrenaline. Enhancement by acetylcholine and by pilocarpine of the contractile responses of the guinea-pig isolated vas deferens to hypogastric nerve and transmural stimulation and to exogenous (minus)-noradrenaline was examined. At high concentration (600 nM) acetylcholine enhanced responses in the order:hypogastric nerve greater than transmural greater than exogenous (minus)-noradrenaline. Pilocarpine produced a similar maximal degree of enchancement with all three stimuli. All these effects were reversibly inhibited by 1-4 mum atropine, a concentration which alone did not affected responses to the stimuli. Pilocarpine (50-400 muM) gave a concentration-related inhibition of the enhancement of responses to hypogastric nerve stimulation by 600 nM acetylcholine."}
{"id": "PMID:237082", "title": "Generation of prostaglandin E-like material by the guinea-pig trachea contracted by histamine.", "content": "Challenges of the superfused (1 ml min-1) trachea with histamine (100-200 mug) result in the release of prostaglandin E-like material (3-25 ng in terms of prostaglandin E2) but no prostaglandin F-like activity has been detected in the superfusate. This release is blocked by indomethacin (1mug ml-1) and then the contractile action of histamine is enhanced. It is concluded that the release of a prostaglandin E-like material by histamine from tracheal smooth muscles is a self-defensive mechanism protecting against the strong constriction of airways. The maximal relaxation of trachea by isoprenaline (50-500 mug) is not accompanied by the release of a prostaglandin-like material.", "contents": "Generation of prostaglandin E-like material by the guinea-pig trachea contracted by histamine. Challenges of the superfused (1 ml min-1) trachea with histamine (100-200 mug) result in the release of prostaglandin E-like material (3-25 ng in terms of prostaglandin E2) but no prostaglandin F-like activity has been detected in the superfusate. This release is blocked by indomethacin (1mug ml-1) and then the contractile action of histamine is enhanced. It is concluded that the release of a prostaglandin E-like material by histamine from tracheal smooth muscles is a self-defensive mechanism protecting against the strong constriction of airways. The maximal relaxation of trachea by isoprenaline (50-500 mug) is not accompanied by the release of a prostaglandin-like material."}
{"id": "PMID:237083", "title": "The pharmacology of Avena sativa.", "content": "The pharmacology of Avena sativa has been investigated in laboratory animals following a report that tincture of Avena sativa reduced the craying for cigarettes in man. The tincture, evaporated to dryness, craving for cigarettes in man. The tincture, evaporated to dryness, re-constituted in an equal volume of water and administered by stomach tube or intraperitoneal injection, antagonized the antinociceptive effect of morphine in two separate test (hot-plate and tail flick). Compared with animals made depedent on morphine alone, mice pretreated with repeated injections of morphine plus extract passed a smaller number of stools and tended to jump less after administration of nalorphine. The pressor response to intravenously administered nicotine in urethane-anaesthetized rats was also antagonized by prior administration of Avena sativa. However, the aqueous extract prepared from the tincture did not affect the seizure threshold to bemegride or nicotine or the sleeping time induced by barbitone sodium.", "contents": "The pharmacology of Avena sativa. The pharmacology of Avena sativa has been investigated in laboratory animals following a report that tincture of Avena sativa reduced the craying for cigarettes in man. The tincture, evaporated to dryness, craving for cigarettes in man. The tincture, evaporated to dryness, re-constituted in an equal volume of water and administered by stomach tube or intraperitoneal injection, antagonized the antinociceptive effect of morphine in two separate test (hot-plate and tail flick). Compared with animals made depedent on morphine alone, mice pretreated with repeated injections of morphine plus extract passed a smaller number of stools and tended to jump less after administration of nalorphine. The pressor response to intravenously administered nicotine in urethane-anaesthetized rats was also antagonized by prior administration of Avena sativa. However, the aqueous extract prepared from the tincture did not affect the seizure threshold to bemegride or nicotine or the sleeping time induced by barbitone sodium."}
{"id": "PMID:237084", "title": "The pharmacology of 14-hydroxyazidomorphine.", "content": "6-Deoxy-6-dihydroazido-14-hydroxyisomorphine (14-hydroxyazidomorphine) was synthesized, its analgesic potency in mice and rats, its antitussive effect in rats and its dependence liability in mice, rats and monkeys were studied. Azidomorphine the 14-nonhydroxylated parent molecule, morphine, hydromorphone and oxymorphone were used for comparison. 14-Hdroxyazidomorphine proved to be as potent an analgesic as azidomorphine, even more potent as an antitussive, and showed the same low tolerance and dependence capacity. It was 11-6 times less toxic than azidomorphine in mice and 6-5 times less toxic in rats.", "contents": "The pharmacology of 14-hydroxyazidomorphine. 6-Deoxy-6-dihydroazido-14-hydroxyisomorphine (14-hydroxyazidomorphine) was synthesized, its analgesic potency in mice and rats, its antitussive effect in rats and its dependence liability in mice, rats and monkeys were studied. Azidomorphine the 14-nonhydroxylated parent molecule, morphine, hydromorphone and oxymorphone were used for comparison. 14-Hdroxyazidomorphine proved to be as potent an analgesic as azidomorphine, even more potent as an antitussive, and showed the same low tolerance and dependence capacity. It was 11-6 times less toxic than azidomorphine in mice and 6-5 times less toxic in rats."}
{"id": "PMID:237085", "title": "Emulsion stabilization by non-ionic surfactants: the relevance of surfactant cloud point.", "content": "The effect of various additives, electrolytes and non-electrolytes, on the cloud point of non-ionic surfactants has been studied. Additives which salt-out the polyoxyethylene chains of the surfactants cause decreased stability of oil-in-water emulsions by decreasing the true hydrophile-lipophile balance (HLB) of the surfactant; additives such as sodium iodide and propanol salt-in the non-ionic surfactants and result in an increase in the effective or true HLB of the system. The latter additives do not increase the hydration of the polyoxyethylene chains but their effect must be on the structure of water so that the heat of hydration of the chains is altered. Experiments with free films of the aqueous surfactant (Brij 96) show that thinning rates are markedly affected by the additives, but there is little effect on the equilibrium thickness of the films (ca 11 nm). Nonetheless the thickness at the transition from thick film to equilibrium black film decreases with increasing cloud point of the solution indicating increased stability. The importance of structure formation in the liquid film separating the emulsion globules was demonstrated.", "contents": "Emulsion stabilization by non-ionic surfactants: the relevance of surfactant cloud point. The effect of various additives, electrolytes and non-electrolytes, on the cloud point of non-ionic surfactants has been studied. Additives which salt-out the polyoxyethylene chains of the surfactants cause decreased stability of oil-in-water emulsions by decreasing the true hydrophile-lipophile balance (HLB) of the surfactant; additives such as sodium iodide and propanol salt-in the non-ionic surfactants and result in an increase in the effective or true HLB of the system. The latter additives do not increase the hydration of the polyoxyethylene chains but their effect must be on the structure of water so that the heat of hydration of the chains is altered. Experiments with free films of the aqueous surfactant (Brij 96) show that thinning rates are markedly affected by the additives, but there is little effect on the equilibrium thickness of the films (ca 11 nm). Nonetheless the thickness at the transition from thick film to equilibrium black film decreases with increasing cloud point of the solution indicating increased stability. The importance of structure formation in the liquid film separating the emulsion globules was demonstrated."}
{"id": "PMID:237086", "title": "Aggregation of antihistamines in aqueous solution. The effect of electrolyte on the miscellar properties of some diphenylmethane derivatives.", "content": "The effect of sodium chloride on the micellar properties of the antihistamines, dephenhydramine hydrochloride, bromodiphenhydramine hydrochloride, chlorcyclizine hydrochloride and diphenylpyraline hydrochloride in aqueous solution has been investigated by light scattering and viscometric methods. The drugs behaved as typical ionic surfactants showing an increase in aggregation number and decrease in critical micelle concentration as the electrolyte concentration was increased over the range 0.05 to 0.154 mol kg-minus1. A linear relation between log critical micelle concentration and log counterion concentration was established, from which values of the degree of ionization and the free energy of micellization were calculated. The intrinsic viscosity was decreased by the addition of electrolyte and this has been attributed to a decrease in micellar hydration due to a removal of hydrogen-bonded water.", "contents": "Aggregation of antihistamines in aqueous solution. The effect of electrolyte on the miscellar properties of some diphenylmethane derivatives. The effect of sodium chloride on the micellar properties of the antihistamines, dephenhydramine hydrochloride, bromodiphenhydramine hydrochloride, chlorcyclizine hydrochloride and diphenylpyraline hydrochloride in aqueous solution has been investigated by light scattering and viscometric methods. The drugs behaved as typical ionic surfactants showing an increase in aggregation number and decrease in critical micelle concentration as the electrolyte concentration was increased over the range 0.05 to 0.154 mol kg-minus1. A linear relation between log critical micelle concentration and log counterion concentration was established, from which values of the degree of ionization and the free energy of micellization were calculated. The intrinsic viscosity was decreased by the addition of electrolyte and this has been attributed to a decrease in micellar hydration due to a removal of hydrogen-bonded water."}
{"id": "PMID:237087", "title": "The evaluation of a column-type dissolution apparatus.", "content": "An improved column-type dissolution apparatus is described. The column of the apparatus is built from standard screw-cap connected \"Sovirel\" glass tubes which should enable inter-apparatus variability to be reduced. The main problem with this type of device is the build up to back pressure as fragments from the disintegrating solid dosage form progressively block the filtration system, itself necessary to stop the solution process and present the solution for analysis. A simple type of light-activated switch is therefore used which works across the indicator float of a flow meter to drive a motor connected to a needle valve. As the float falls the motor is switched on to open the valve and increase the flow rate until the float rises again and causes the motor to switch off. Observation on the dissolution characteristic of dyed lactose tablets and the injection of dye solutions into the flowing stream of liquid around tablets showed that there was back-flow of solution at Reynolds Numbers below 10 but visible instability to flow at Re greater than 100. Over a range of flow rates between Re 10-70 the mass of drug released at a given time was a direct function of flow rate for a film coated product but an inverse function for a sugar coated tablet. The results are discussed in relation to the main problems which can be experienced with a column-type dissolution apparatus.", "contents": "The evaluation of a column-type dissolution apparatus. An improved column-type dissolution apparatus is described. The column of the apparatus is built from standard screw-cap connected \"Sovirel\" glass tubes which should enable inter-apparatus variability to be reduced. The main problem with this type of device is the build up to back pressure as fragments from the disintegrating solid dosage form progressively block the filtration system, itself necessary to stop the solution process and present the solution for analysis. A simple type of light-activated switch is therefore used which works across the indicator float of a flow meter to drive a motor connected to a needle valve. As the float falls the motor is switched on to open the valve and increase the flow rate until the float rises again and causes the motor to switch off. Observation on the dissolution characteristic of dyed lactose tablets and the injection of dye solutions into the flowing stream of liquid around tablets showed that there was back-flow of solution at Reynolds Numbers below 10 but visible instability to flow at Re greater than 100. Over a range of flow rates between Re 10-70 the mass of drug released at a given time was a direct function of flow rate for a film coated product but an inverse function for a sugar coated tablet. The results are discussed in relation to the main problems which can be experienced with a column-type dissolution apparatus."}
{"id": "PMID:237088", "title": "Microiontophoretic studies of the effects of false transmitter candidates and amphetamine on cerebellar Purkinje cells.", "content": "The effects of microiontophoretic applications of equivalent doses (ejection times and currents) of noradrenaline, amphetamine, octopamine and p-hydroxynorephedrine on the spontaneous firing of Purkinje and unidentified cells in the cerebellum of rats were examined. In addition, the effects of amphetamine of Purkinje cells were examined in animals pretreated with the tyrosine hydroxylase inhibitor, alpha-methyltyrosine (alpha-MpT) or with a combination of reserpine plus alpha-MpT. The results indicate that the \"false transmitters\" are weak agonists when compared to noradrenaline in inhibiting the firing of Purkinje cells. The results of the iontophoretic studies with amphetamine are not consistent with a pre-synaptic releasing effect by amphetamine at noradrenergic synapses in the cns since the efficacy of amphetamine on Purkinje cells was unaltered after pretreatment with alpha-MpT or alpha-MpT plus reserpine.", "contents": "Microiontophoretic studies of the effects of false transmitter candidates and amphetamine on cerebellar Purkinje cells. The effects of microiontophoretic applications of equivalent doses (ejection times and currents) of noradrenaline, amphetamine, octopamine and p-hydroxynorephedrine on the spontaneous firing of Purkinje and unidentified cells in the cerebellum of rats were examined. In addition, the effects of amphetamine of Purkinje cells were examined in animals pretreated with the tyrosine hydroxylase inhibitor, alpha-methyltyrosine (alpha-MpT) or with a combination of reserpine plus alpha-MpT. The results indicate that the \"false transmitters\" are weak agonists when compared to noradrenaline in inhibiting the firing of Purkinje cells. The results of the iontophoretic studies with amphetamine are not consistent with a pre-synaptic releasing effect by amphetamine at noradrenergic synapses in the cns since the efficacy of amphetamine on Purkinje cells was unaltered after pretreatment with alpha-MpT or alpha-MpT plus reserpine."}
{"id": "PMID:237089", "title": "Intra- and extraneuronal formation of the two major noradrenaline metabolites in the cns of rats.", "content": "The two major noradrenaline metabolites in the rat brain, total 3-methoxy-4-hydroxyphenylglycol (MOPEG) and total 3,4-dihydroxyphenylglycol (DOPEG), were measured by a new analytical procedure after intraventricular (i.v.t.) injection of (3-H) noradrenaline or (3-H) dopamine. I.v.t. injection of (3-H) noradrenaline to rats with a 6-hydroxydopamine-induced destruction of nerve terminals in the central nervous system, resulted in an increased accumulation of 3-H-MOPEG compared to 3-H-DOPEG. On the contrary, reserpine induced a greater increase in 3-H-DOPEG than in 3-H-MOPEG accumulation when these two metabolites were formed from (3-H) noradrenaline synthesized in vivo by i.v.t. injection of (3-H) dopamine. These results indicate that the formation of DOPEG and MOPEG occur with some preference intra- and extraneuronally, respectively. The results, however, also show that these two formations sites should not be considered as specific.", "contents": "Intra- and extraneuronal formation of the two major noradrenaline metabolites in the cns of rats. The two major noradrenaline metabolites in the rat brain, total 3-methoxy-4-hydroxyphenylglycol (MOPEG) and total 3,4-dihydroxyphenylglycol (DOPEG), were measured by a new analytical procedure after intraventricular (i.v.t.) injection of (3-H) noradrenaline or (3-H) dopamine. I.v.t. injection of (3-H) noradrenaline to rats with a 6-hydroxydopamine-induced destruction of nerve terminals in the central nervous system, resulted in an increased accumulation of 3-H-MOPEG compared to 3-H-DOPEG. On the contrary, reserpine induced a greater increase in 3-H-DOPEG than in 3-H-MOPEG accumulation when these two metabolites were formed from (3-H) noradrenaline synthesized in vivo by i.v.t. injection of (3-H) dopamine. These results indicate that the formation of DOPEG and MOPEG occur with some preference intra- and extraneuronally, respectively. The results, however, also show that these two formations sites should not be considered as specific."}
{"id": "PMID:237090", "title": "Neuromuscular actions of edrophonium in the lateral segmental tail muscle of the rat in vivo.", "content": "The actions of edrophonium on neuromuscular transmission in vivo have been studied using the lateral segmental tail muscles of the rat. The drug produced an increase in amplitude of the miniature endplate potentials (m.e.p.p.s) without an effect on their frequency and increased the amplitude of the end-plate potentials (e.p.p.s) without increasing quantal release of transmitter. It is concluded that the anticholinesterase action of this drug in vivo facilitates neuromuscular transmission, which confirms many of the findings from in vitro studies.", "contents": "Neuromuscular actions of edrophonium in the lateral segmental tail muscle of the rat in vivo. The actions of edrophonium on neuromuscular transmission in vivo have been studied using the lateral segmental tail muscles of the rat. The drug produced an increase in amplitude of the miniature endplate potentials (m.e.p.p.s) without an effect on their frequency and increased the amplitude of the end-plate potentials (e.p.p.s) without increasing quantal release of transmitter. It is concluded that the anticholinesterase action of this drug in vivo facilitates neuromuscular transmission, which confirms many of the findings from in vitro studies."}
{"id": "PMID:237091", "title": "A simultaneous determination of acetylsalicylic acid, salicylic acid and salicylamide in plasma by gas liquid chromatography.", "content": "A novel method for the simultaneous determination of acetylsalicylic acid, salicylic acid and salicylamide in biological fluids by gas liquid chromatography is described. The assay has been used to determine the plasma concentration of salicylates in 10 volunteers after oral ingestion of three commercially available aspirin-containing formulations. No difficulty was encountered in determining low concentrations of acetylsalicylic acid in the presence of higher concentrations of salicylic acid. The in vivo plasma half life of acetylsalicylic acid in man was found to be 15.5 min.", "contents": "A simultaneous determination of acetylsalicylic acid, salicylic acid and salicylamide in plasma by gas liquid chromatography. A novel method for the simultaneous determination of acetylsalicylic acid, salicylic acid and salicylamide in biological fluids by gas liquid chromatography is described. The assay has been used to determine the plasma concentration of salicylates in 10 volunteers after oral ingestion of three commercially available aspirin-containing formulations. No difficulty was encountered in determining low concentrations of acetylsalicylic acid in the presence of higher concentrations of salicylic acid. The in vivo plasma half life of acetylsalicylic acid in man was found to be 15.5 min."}
{"id": "PMID:237092", "title": "The gas chromatographic determination of atenolol in biological samples.", "content": "Methods are described for the gas chromatographic determination of the B-adrenoceptor blocking agent atenolol (ICI 66,082 Tenormin) in whole blood, serum, tissue and urine. The method involves the extraction of the free base from the prepared biological sample into an organic solvent mixture. Further purification is done by backextracting the base into dilute acid from which, after basification it is extracted again into organic solvent. Any atenolol in the residue remaining after solvent evaporation is converted into a heptafluorobutyrate derivative ready for gas chromatography. Use of an electron-capture detector enables concentrations as low as 0.01 mug ml-minus 1 body fluid and 0.04 mug ml-minus 1 tissue to be measured.", "contents": "The gas chromatographic determination of atenolol in biological samples. Methods are described for the gas chromatographic determination of the B-adrenoceptor blocking agent atenolol (ICI 66,082 Tenormin) in whole blood, serum, tissue and urine. The method involves the extraction of the free base from the prepared biological sample into an organic solvent mixture. Further purification is done by backextracting the base into dilute acid from which, after basification it is extracted again into organic solvent. Any atenolol in the residue remaining after solvent evaporation is converted into a heptafluorobutyrate derivative ready for gas chromatography. Use of an electron-capture detector enables concentrations as low as 0.01 mug ml-minus 1 body fluid and 0.04 mug ml-minus 1 tissue to be measured."}
{"id": "PMID:237093", "title": "A rapid gas-liquid chromatographic estimation of nicotine in biological fluids.", "content": "A rapid gas-liquid chromatographic method for the estimation of nicotine in plasma is described. Nicotine is extracted from alkalinized plasma into diethyl ether. This is then concentrated by evaporation and, after an acid back extraction is re-extracted into n-heptane (nitrogen detector) or dichloromethane (flame ionization detector) before injection onto the gas chromatography. Thirty samples a day can be analysed by this method which enables concentrations of 0.1 ng ml- minus 1 nicotine to be measured. It is thus possible to measure nicotine in plasma and urine samples from non-smokers.", "contents": "A rapid gas-liquid chromatographic estimation of nicotine in biological fluids. A rapid gas-liquid chromatographic method for the estimation of nicotine in plasma is described. Nicotine is extracted from alkalinized plasma into diethyl ether. This is then concentrated by evaporation and, after an acid back extraction is re-extracted into n-heptane (nitrogen detector) or dichloromethane (flame ionization detector) before injection onto the gas chromatography. Thirty samples a day can be analysed by this method which enables concentrations of 0.1 ng ml- minus 1 nicotine to be measured. It is thus possible to measure nicotine in plasma and urine samples from non-smokers."}
{"id": "PMID:237106", "title": "Hydrolysis of fatty acid esters of acetaminophen in buffered pancreatic lipase systmes I.", "content": "A series of fatty acid esters of acetaminophen were prepared beginning with acetate, the propionate, and all even-numbered fatty acids and going through the octadecanoate. The enzymatic hydrolysis of all derivatives was studied in vitro with varying amounts of lipase assed to the hydrolysis mixtures. Under the conditions of the in vitro hydrolysis, it was observed that all derivatives were hydrolyzed more readily in an aqueous medium at pH 7.8. A positive relationship was seen between the hydrolysis rates and the concentration of lipase at this pH. There was a negative relationship between the chain length of the acyl moiety and the corresponding hydrolysis rates. The short chain esters were hydrolyzed at rates many times more rapid than the long chain esters. The intermediate chain-lenght ester, p-acetamidophenyl decanoate, p-acetamidophenyl laurate, and p-acetamidophenyl myristate, were hydrolyzed at intermedediate time periods extending over 12 hr, approaching completion at 97.5, 87.5, and 80.5%, respectively, when 18 Wilson units of lipase was used in each milliliter of hydrolysis mixture. The longer chain esters, p-acetamidophenyl palmitate and p-acetamidophenyl stearate, were hydrolyzed to the extent of 16 and 8%, respectively, over 12 hr under the same in vitro conditions.", "contents": "Hydrolysis of fatty acid esters of acetaminophen in buffered pancreatic lipase systmes I. A series of fatty acid esters of acetaminophen were prepared beginning with acetate, the propionate, and all even-numbered fatty acids and going through the octadecanoate. The enzymatic hydrolysis of all derivatives was studied in vitro with varying amounts of lipase assed to the hydrolysis mixtures. Under the conditions of the in vitro hydrolysis, it was observed that all derivatives were hydrolyzed more readily in an aqueous medium at pH 7.8. A positive relationship was seen between the hydrolysis rates and the concentration of lipase at this pH. There was a negative relationship between the chain length of the acyl moiety and the corresponding hydrolysis rates. The short chain esters were hydrolyzed at rates many times more rapid than the long chain esters. The intermediate chain-lenght ester, p-acetamidophenyl decanoate, p-acetamidophenyl laurate, and p-acetamidophenyl myristate, were hydrolyzed at intermedediate time periods extending over 12 hr, approaching completion at 97.5, 87.5, and 80.5%, respectively, when 18 Wilson units of lipase was used in each milliliter of hydrolysis mixture. The longer chain esters, p-acetamidophenyl palmitate and p-acetamidophenyl stearate, were hydrolyzed to the extent of 16 and 8%, respectively, over 12 hr under the same in vitro conditions."}
{"id": "PMID:237107", "title": "Kinetics of sulfite-induced anaerobic degradation of epinephrine.", "content": "The rate constant-pH profile of the rate of sulfite-induced disappearance of epinephrine from an aqueous solution under anaerobic conditions was determined at 81 degrees in the 3.63-5.00 pH range at the ionic strength of 0.2. The profile shows a linear relationship with a positive slope. The anaerobic rate shows buffer catalysis above pH 4.4 Metabisulfite was found to be more catalytic than either bisulfite or acetone bisulfite. The concentration of epinephrine used was 5.5 times 10- minus 5 mole/liter.", "contents": "Kinetics of sulfite-induced anaerobic degradation of epinephrine. The rate constant-pH profile of the rate of sulfite-induced disappearance of epinephrine from an aqueous solution under anaerobic conditions was determined at 81 degrees in the 3.63-5.00 pH range at the ionic strength of 0.2. The profile shows a linear relationship with a positive slope. The anaerobic rate shows buffer catalysis above pH 4.4 Metabisulfite was found to be more catalytic than either bisulfite or acetone bisulfite. The concentration of epinephrine used was 5.5 times 10- minus 5 mole/liter."}
{"id": "PMID:237108", "title": "Systems approach to vaginal delivery of drugs I: development of in situ vaginal drug absorption procedure.", "content": "In the framework of the development of drug delivery systems for locally administered contraceptive drugs, a reliable method that can afford quantitative evaluation of drug absorption behavior was explored using the rabit doe. A system was constructed based upon perfusing the drug solution in the vaginal tract. For this purpose, a \"rib-cage\" type cell was constructed and surgically implanted in the rabbit prior to an experiment. The primary purpose of the present paper is to evaluate the method, including the surgical operation and the perfusion system. The absorption experiments were carried out using n-butanol-1minus 14C as the model solute to survey the reproducibility of the absorption behavior. Experiments were conducted with a number of rabbits on several successive days to determine the day-to-day and animal-to-animal variations. The drug disappearance in the reservoir followed first-order kinetics from which the apparent permeability coefficient was calculated. The results indicated that a set of experiments may be carried out on a single animal and that the method generally affords rather high precision.", "contents": "Systems approach to vaginal delivery of drugs I: development of in situ vaginal drug absorption procedure. In the framework of the development of drug delivery systems for locally administered contraceptive drugs, a reliable method that can afford quantitative evaluation of drug absorption behavior was explored using the rabit doe. A system was constructed based upon perfusing the drug solution in the vaginal tract. For this purpose, a \"rib-cage\" type cell was constructed and surgically implanted in the rabbit prior to an experiment. The primary purpose of the present paper is to evaluate the method, including the surgical operation and the perfusion system. The absorption experiments were carried out using n-butanol-1minus 14C as the model solute to survey the reproducibility of the absorption behavior. Experiments were conducted with a number of rabbits on several successive days to determine the day-to-day and animal-to-animal variations. The drug disappearance in the reservoir followed first-order kinetics from which the apparent permeability coefficient was calculated. The results indicated that a set of experiments may be carried out on a single animal and that the method generally affords rather high precision."}
{"id": "PMID:237110", "title": "Vasoconstriction of the isolated rabbit ear artery caused by nicotinic agonists acting on adrenergic neurons.", "content": "In the perfused isolated central ear artery of the rabbit, nicotine, acetylcholine (ACh), tetramethylammonium (TMA) and carbachol (CCh) at high concentrations (greater than 1 mug/ml) produced transient vasoconstriction. The order of potency was: nicotine greater than ACh greater than TMA greater than CCh. Over the concentration range used, all of the agonists except ACh gave bell-shaped log concentration-response curves. Methacholine did not cause vasoconstriction. The response to ACh, TMA or CCh, but not to nicotine, was potentiated by atropine (0.1-1.0 mug/ml). Tetraethylammonium, hexamethonium, mecamylamine and d-tubocurarine blocked the response to the nicotinic agonists and to nerve stimulation. Ear arteries from reserpine-treated rabbits gave no, or very little, constrictor response to the nicotinic agonists or to nerve stimulation. These findings support the conclusion that the vasoconstriction produced by the nicotinic agonists is mediated by norepinephrine released from adrenergic nerve terminals as a result of the action of the agents on neuronal nicotinic receptors located at or near the terminals. The potentiation by atropine of the constrictor response to ACh, TMA and CCh is attributed to the blockade by atropine of neuronal muscarinic receptors on which these agonists act to inhibit the release of norepinephrine.", "contents": "Vasoconstriction of the isolated rabbit ear artery caused by nicotinic agonists acting on adrenergic neurons. In the perfused isolated central ear artery of the rabbit, nicotine, acetylcholine (ACh), tetramethylammonium (TMA) and carbachol (CCh) at high concentrations (greater than 1 mug/ml) produced transient vasoconstriction. The order of potency was: nicotine greater than ACh greater than TMA greater than CCh. Over the concentration range used, all of the agonists except ACh gave bell-shaped log concentration-response curves. Methacholine did not cause vasoconstriction. The response to ACh, TMA or CCh, but not to nicotine, was potentiated by atropine (0.1-1.0 mug/ml). Tetraethylammonium, hexamethonium, mecamylamine and d-tubocurarine blocked the response to the nicotinic agonists and to nerve stimulation. Ear arteries from reserpine-treated rabbits gave no, or very little, constrictor response to the nicotinic agonists or to nerve stimulation. These findings support the conclusion that the vasoconstriction produced by the nicotinic agonists is mediated by norepinephrine released from adrenergic nerve terminals as a result of the action of the agents on neuronal nicotinic receptors located at or near the terminals. The potentiation by atropine of the constrictor response to ACh, TMA and CCh is attributed to the blockade by atropine of neuronal muscarinic receptors on which these agonists act to inhibit the release of norepinephrine."}
{"id": "PMID:237111", "title": "Effects of beta adrenergic blocking agents on erythropoietin production in rabbits exposed to hypoxia.", "content": "The effects of dl-propranolol, d-propranolol, butoxamine or practolol on erythropoietin (ESF) production in rabbits exposed to hypoxia (0.42 atmosphere) for 18 hours were investigated. Rabbits treated with dl-propranolol (4 or 8 mg/kg i.p.) or butoxamine (15 or 30 mg/kg i.p.) produced significantly less ESF in response to hypoxia than did saline-treated control animals. ESF production in rabbits given d-propranolol or practolol during hypoxia was not significantly different from that of control animals exposed to hypoxia. Based on the proposed selectivity of butoxamine for beta2 adrenergic receptors and of practolol for beta1 adrenergic receptors, it is suggested that ESF production in rabbits exposed to hypoxia may involve the activation of beta2 adrenergic receptors.", "contents": "Effects of beta adrenergic blocking agents on erythropoietin production in rabbits exposed to hypoxia. The effects of dl-propranolol, d-propranolol, butoxamine or practolol on erythropoietin (ESF) production in rabbits exposed to hypoxia (0.42 atmosphere) for 18 hours were investigated. Rabbits treated with dl-propranolol (4 or 8 mg/kg i.p.) or butoxamine (15 or 30 mg/kg i.p.) produced significantly less ESF in response to hypoxia than did saline-treated control animals. ESF production in rabbits given d-propranolol or practolol during hypoxia was not significantly different from that of control animals exposed to hypoxia. Based on the proposed selectivity of butoxamine for beta2 adrenergic receptors and of practolol for beta1 adrenergic receptors, it is suggested that ESF production in rabbits exposed to hypoxia may involve the activation of beta2 adrenergic receptors."}
{"id": "PMID:237112", "title": "Oxilorphan (l-N-cyclopropylmethyl-3,14-dihydroxymorphinan): a new synthetic narcotic antagonist.", "content": "Oxilorphan is a fully synthetic morphinan derivative containing the 14-hydroxy group characteristics of naloxone and naltrexone. As a narcotic antagonist, oxilorphan was 4 times more potent than dl-cyclazocine, equipotent to naloxone and about one-fourth as potent as naltrexone parenterally. Duration studies in rodents were inconclusive, but in antagonism of morphine analgesia and miosis in the dog, oxilorphan was longer acting than naloxone and equivalent to dl-cyclazocine. Oxilorphan was inactive in the conventional animal thermal analgesic tests. However, oxilone did exhibit relatively weak analgesic activity in preventing phenylquinone-induced abdominal contraction at doses about 700 times higher than those required for antagonist activity. The analgesic potency of oxilorphan was only 120 and 1/300 the potency of morphine and dl-cyclazocine, respectively, but was significantly greater than naltrexone and naloxone. Mice chronically treated with increasing doses of oxilorphan failed to exhibit withdrawal jumping after naloxone challenge. General central nervous system activity studies showed oxilorphan to be relatively free from central side effects at doses at which dl-cyclazocine produced pronounced effects.", "contents": "Oxilorphan (l-N-cyclopropylmethyl-3,14-dihydroxymorphinan): a new synthetic narcotic antagonist. Oxilorphan is a fully synthetic morphinan derivative containing the 14-hydroxy group characteristics of naloxone and naltrexone. As a narcotic antagonist, oxilorphan was 4 times more potent than dl-cyclazocine, equipotent to naloxone and about one-fourth as potent as naltrexone parenterally. Duration studies in rodents were inconclusive, but in antagonism of morphine analgesia and miosis in the dog, oxilorphan was longer acting than naloxone and equivalent to dl-cyclazocine. Oxilorphan was inactive in the conventional animal thermal analgesic tests. However, oxilone did exhibit relatively weak analgesic activity in preventing phenylquinone-induced abdominal contraction at doses about 700 times higher than those required for antagonist activity. The analgesic potency of oxilorphan was only 120 and 1/300 the potency of morphine and dl-cyclazocine, respectively, but was significantly greater than naltrexone and naloxone. Mice chronically treated with increasing doses of oxilorphan failed to exhibit withdrawal jumping after naloxone challenge. General central nervous system activity studies showed oxilorphan to be relatively free from central side effects at doses at which dl-cyclazocine produced pronounced effects."}
{"id": "PMID:237113", "title": "The pharmacology of batrachotoxin. VII. Structure-activity relationships and the effects of pH.", "content": "The effects of the depolarizing agent, batrachotoxin (BTX), and of various analogs were studied on rat phrenic nerve-diaphragm muscle preparations at 37 degrees C. The structural modifications of BTX included: 1) replacement of the 20alpha-pyrrole-3-carboxylate moiety; 2) alterations of substituents on the pyrrole moiety; 3) clevage of the 3alpha, 9alpha-hemiketal linkage; and 4) quaternization of the tertiary nitrogen of BTX. All of the compounds except batrachotoxinin A (BTX-A), which lacks the 20alpha-substituent, depolarized the postsynaptic membrane, transiently increased the frequency of spontaneous transmitter release to 400 to 600 sec- minus 1 and finally produced blockade of the directly and indirectly elicited muscle twitches. Of the compounds tested, only BTX-A potentiated the muscle twitches. The concentration which elicits a 50% depolarization of the muscle membrane in 1 hour was determined for all the compounds except for BTX-A and for dihydrobatrachotoxin which lacks the 3alpha, 9alpha-hemiketal linkage; these two analogs never depolarized the postsynaptic membrane by more than 10 to 15%. BTX, the 20alpha-2, 4, 5-trimethylpyrrole-3-carboxylate of BTX-A and the 20alpha-ester of BTX-A with 2-ethyl-4-methylpyrrole-3-carboxylic acid (homobatrachotoxin) were the three most potent toxins with doses of 4.5, 12 and 18 times 10- minus 9 M eliciting a 50% membrane depolarization in 1 hour. The quaternary derivative of BTX, the 20alpha-4, 5-dimethylpyrrole-3-carboxylate of BTX-A and 20alpha-2,4-dimethyl-5-acetylpyrrole-3-carboxylate of BTX-A were 24-, 65- and 110-fold less potent than BTX as depolarizing agents, whereas the 20alpha-p-bromobenzoate of BTX-A was 220-fold less potent. Each of these derivatives had the ability to increase sodium permeability since the increase in spontaneous miniature end-plate potential frequency and membrane depolarization were reversed by tetrodotoxin or by reducing the external sodium concentration. BTX was found to be more effective at alkaline pH (pH 9.0), at which it exists almost entirely in the un-ionized form, than at physiological or acidic pH(6.0). The results indicate that the analogs of BTX act by a mechanism similar to that of the parent compound, but that their potency differs and certain compounds may have a more selective action on either the pre- or postsynaptic membrane. For maximal depolarizing activity, a substituted pyrrole moiety is necessary at the 20alpha-position of BTX-A and 3alpha, 9alpha-hemiketal linkage must remain intact providing rigidity for the pentacyclic steroid nucleus.", "contents": "The pharmacology of batrachotoxin. VII. Structure-activity relationships and the effects of pH. The effects of the depolarizing agent, batrachotoxin (BTX), and of various analogs were studied on rat phrenic nerve-diaphragm muscle preparations at 37 degrees C. The structural modifications of BTX included: 1) replacement of the 20alpha-pyrrole-3-carboxylate moiety; 2) alterations of substituents on the pyrrole moiety; 3) clevage of the 3alpha, 9alpha-hemiketal linkage; and 4) quaternization of the tertiary nitrogen of BTX. All of the compounds except batrachotoxinin A (BTX-A), which lacks the 20alpha-substituent, depolarized the postsynaptic membrane, transiently increased the frequency of spontaneous transmitter release to 400 to 600 sec- minus 1 and finally produced blockade of the directly and indirectly elicited muscle twitches. Of the compounds tested, only BTX-A potentiated the muscle twitches. The concentration which elicits a 50% depolarization of the muscle membrane in 1 hour was determined for all the compounds except for BTX-A and for dihydrobatrachotoxin which lacks the 3alpha, 9alpha-hemiketal linkage; these two analogs never depolarized the postsynaptic membrane by more than 10 to 15%. BTX, the 20alpha-2, 4, 5-trimethylpyrrole-3-carboxylate of BTX-A and the 20alpha-ester of BTX-A with 2-ethyl-4-methylpyrrole-3-carboxylic acid (homobatrachotoxin) were the three most potent toxins with doses of 4.5, 12 and 18 times 10- minus 9 M eliciting a 50% membrane depolarization in 1 hour. The quaternary derivative of BTX, the 20alpha-4, 5-dimethylpyrrole-3-carboxylate of BTX-A and 20alpha-2,4-dimethyl-5-acetylpyrrole-3-carboxylate of BTX-A were 24-, 65- and 110-fold less potent than BTX as depolarizing agents, whereas the 20alpha-p-bromobenzoate of BTX-A was 220-fold less potent. Each of these derivatives had the ability to increase sodium permeability since the increase in spontaneous miniature end-plate potential frequency and membrane depolarization were reversed by tetrodotoxin or by reducing the external sodium concentration. BTX was found to be more effective at alkaline pH (pH 9.0), at which it exists almost entirely in the un-ionized form, than at physiological or acidic pH(6.0). The results indicate that the analogs of BTX act by a mechanism similar to that of the parent compound, but that their potency differs and certain compounds may have a more selective action on either the pre- or postsynaptic membrane. For maximal depolarizing activity, a substituted pyrrole moiety is necessary at the 20alpha-position of BTX-A and 3alpha, 9alpha-hemiketal linkage must remain intact providing rigidity for the pentacyclic steroid nucleus."}
{"id": "PMID:237114", "title": "Experimental study of a potential anti-asthmatic agent: SCH 15280.", "content": "A forced oscillations technique for measuring total respiratory system resistance was used to quantitate the bronchomotor activity of Sch 15280: (5[4-(N-methyl)-piperidylidine]5H-[1]-benzopyrano[2,3,b]-pyridine maleate) and to compare its potency to that of standard bronchodilator agents. By the intravenous route, Sch 15280 was 48 times more potent than aminophylline and 1/78 as potent as atropine in inhibiting methacholine-induced bronchoconstriction in rabbits. In cats Sch 15280 was 1/12 as potent as ephedrine in inhibiting histamine-induced bronchoconstriction and had a greater protective activity against histamine-induced bronchoconstriction and had a longer duration of action than 0.5% solution of isoproterenol. Statistical tests of parallelism revealed a significant difference between the log dose-response curves of Sch 15280 and ephedrine but not between those of Sch 15280, atropine and aminophylline. The results suggest that Sch 15280 can act via, a nonadrenergic mechanism to block both histaminergically and cholinergically mediated responses in the tracheobronchial tree. This pharmacologie profile may have important therapeutic application in the type I immediate hypersensitivity reactions of man.", "contents": "Experimental study of a potential anti-asthmatic agent: SCH 15280. A forced oscillations technique for measuring total respiratory system resistance was used to quantitate the bronchomotor activity of Sch 15280: (5[4-(N-methyl)-piperidylidine]5H-[1]-benzopyrano[2,3,b]-pyridine maleate) and to compare its potency to that of standard bronchodilator agents. By the intravenous route, Sch 15280 was 48 times more potent than aminophylline and 1/78 as potent as atropine in inhibiting methacholine-induced bronchoconstriction in rabbits. In cats Sch 15280 was 1/12 as potent as ephedrine in inhibiting histamine-induced bronchoconstriction and had a greater protective activity against histamine-induced bronchoconstriction and had a longer duration of action than 0.5% solution of isoproterenol. Statistical tests of parallelism revealed a significant difference between the log dose-response curves of Sch 15280 and ephedrine but not between those of Sch 15280, atropine and aminophylline. The results suggest that Sch 15280 can act via, a nonadrenergic mechanism to block both histaminergically and cholinergically mediated responses in the tracheobronchial tree. This pharmacologie profile may have important therapeutic application in the type I immediate hypersensitivity reactions of man."}
{"id": "PMID:237115", "title": "Effects of 6-hydroxydopamine and reserpine on amphetamine-induced release of norepinephrine in rat cerebral cortex.", "content": "Amphetamine released 3-H-norepinephrine from rat cerebral cortex tissue which had previously accumulated the 3-H-amine. Destruction of noradrenergic nerve endings by pretreatment of the rats with 6-hydroxydopamine inhibited the accumulation of 3-H-norepinephrine by the tissue and reduced the proportion of the 3-H-amine which was released by amphetamine. Inhibition of storage of 3-H-norepinephrine within nerve endings by pretreatment of the animals with reserpine also reduced accumulation of 3-H-norepinephrine but did not reduce the proportion of the accumulated 3-H-amine which was released by amphetamine. The addition of desipramine (an inhibitor of neuronal uptake) further reduced the accumulation of 3-H-norepinephrine in animals pretreated with reserpine but had no further effect in animals pretreated with 6-hydroxydopamine. A greater proportion of the 3-H-norepinephrine was converted to 3-H-deaminated metabolites in tissues of reserpine-treated animals than in the tissues of control or 6-hydroxydopamine-treated rats. Amphetamine-induced release of 3-H-norepinephrine was partially calcium dependent in tissues from control animals. After reserpine treatment, amphetamine-induced release of norepinephrine was independent of calcium, whereas potassium-mediated release was still markedly calcium dependent. These experiments indicate that amphetamine releases 3-H-norepinephrine primarily from storage sites within central adrenergic nerve endings. An analysis of the time course of release from tissues of rats treated with reserpine suggests that amphetamine is equally capable of releasing 3-H-norepinephrine from granular sites which are susceptible to reserpine and from reserpine-insensitive sites.", "contents": "Effects of 6-hydroxydopamine and reserpine on amphetamine-induced release of norepinephrine in rat cerebral cortex. Amphetamine released 3-H-norepinephrine from rat cerebral cortex tissue which had previously accumulated the 3-H-amine. Destruction of noradrenergic nerve endings by pretreatment of the rats with 6-hydroxydopamine inhibited the accumulation of 3-H-norepinephrine by the tissue and reduced the proportion of the 3-H-amine which was released by amphetamine. Inhibition of storage of 3-H-norepinephrine within nerve endings by pretreatment of the animals with reserpine also reduced accumulation of 3-H-norepinephrine but did not reduce the proportion of the accumulated 3-H-amine which was released by amphetamine. The addition of desipramine (an inhibitor of neuronal uptake) further reduced the accumulation of 3-H-norepinephrine in animals pretreated with reserpine but had no further effect in animals pretreated with 6-hydroxydopamine. A greater proportion of the 3-H-norepinephrine was converted to 3-H-deaminated metabolites in tissues of reserpine-treated animals than in the tissues of control or 6-hydroxydopamine-treated rats. Amphetamine-induced release of 3-H-norepinephrine was partially calcium dependent in tissues from control animals. After reserpine treatment, amphetamine-induced release of norepinephrine was independent of calcium, whereas potassium-mediated release was still markedly calcium dependent. These experiments indicate that amphetamine releases 3-H-norepinephrine primarily from storage sites within central adrenergic nerve endings. An analysis of the time course of release from tissues of rats treated with reserpine suggests that amphetamine is equally capable of releasing 3-H-norepinephrine from granular sites which are susceptible to reserpine and from reserpine-insensitive sites."}
{"id": "PMID:237116", "title": "Effect of alpha-methyldopa on dopamine synthesis and release in rat striatum in vitro.", "content": "The effect of alpha-methyldopa and alpha-methyldopamine (alpha-MDA) on the rate of hydroxylation of radioactive tyrosine was studied in striatal slices from rat brain. This was done by measuring the formation of 3-H-H2O as well as the accumulation of 3-H-dopamine (3-H-DA) from L-3, 5-3-H-tyrosine. alpha-Methyldopa, at tissue concentrations similar to those found in vivo after systemic administration, produced a decrease in both 3-H-H2O and 3-H-DA. The marked decrease (91thyldopa injection, also inhibited 3-H-H2O formation. The inhibitory effect of alpha-methyldopa on 3-H-H2O formation was not reduced by the addition of brocresine, which prevents the formation of alpha-MDA. The effects of alpha-methyldopa and alpha-MDA on the release of 3-H-DA that had been taken up into brain slices, was also studied. Although alpha-methyldopa, 1000 muM, did not increase the release of 3H-DA from tissue, alpha-MDA did. However, the latter was more potent in inhibiting 3-H-H2O formation from 3-H-tyrosine than in releasing 3-H-DA. These results, as well as the close similarity between the percent reduction of 3-H-H2O formation and tissue 3-H-DA levels, suggest that alpha-methyldopa decreases tissue levels of dopamine by inhibiting tyrosine hydroxylase activity in DA neurons.", "contents": "Effect of alpha-methyldopa on dopamine synthesis and release in rat striatum in vitro. The effect of alpha-methyldopa and alpha-methyldopamine (alpha-MDA) on the rate of hydroxylation of radioactive tyrosine was studied in striatal slices from rat brain. This was done by measuring the formation of 3-H-H2O as well as the accumulation of 3-H-dopamine (3-H-DA) from L-3, 5-3-H-tyrosine. alpha-Methyldopa, at tissue concentrations similar to those found in vivo after systemic administration, produced a decrease in both 3-H-H2O and 3-H-DA. The marked decrease (91thyldopa injection, also inhibited 3-H-H2O formation. The inhibitory effect of alpha-methyldopa on 3-H-H2O formation was not reduced by the addition of brocresine, which prevents the formation of alpha-MDA. The effects of alpha-methyldopa and alpha-MDA on the release of 3-H-DA that had been taken up into brain slices, was also studied. Although alpha-methyldopa, 1000 muM, did not increase the release of 3H-DA from tissue, alpha-MDA did. However, the latter was more potent in inhibiting 3-H-H2O formation from 3-H-tyrosine than in releasing 3-H-DA. These results, as well as the close similarity between the percent reduction of 3-H-H2O formation and tissue 3-H-DA levels, suggest that alpha-methyldopa decreases tissue levels of dopamine by inhibiting tyrosine hydroxylase activity in DA neurons."}
{"id": "PMID:237117", "title": "Induction of tyrosine hydroxylase elicited by beta adrenergic receptor agonists in normal and decentralized sympathetic ganglia: role of cyclic 3',5' - adenosine monophosphate.", "content": "A subcutaneous injection of an oil suspension of l-epinephrine (270 mumol/kg), dopamine (270 mumol/kg) or l-norepinephrine (270 mumol/kg), when administered with phenoxybenzamine (32 mumol/kg i.p.) to blocl alpha adrenergic effects, increases the cyclic 3', 5'-adenosine monophosphate (cAMP) content in superior cervical ganglia (SCG) of rats. The increase is highest after l-epinephrine and dopamine and is barely detectable after l-norepinephrine; it lasts longer than 2 hours after l-epinephrine, about 30 minutes after dopamine and is fleeting after l-norepinephrine. The duration of the increase in cAMP elicited by l-epinephrine in SCG of rats is dose-related. Furthermore, when the cAMP increase lasts longer than 90 minutes, 48 hours later the tyrosine hydroxylase (TH) activity in SCG is increased. l0Epinephrine (150 mol/kg s.c.) induces TH in decentralized ganglia. One injection of l-isoproterenol (77 mol/kg i.p.) increases cAMP concentrations in intact and decentralized SCG. This increase lasts only 30 minutes and fails to induce TH 48 hours later. However, if the increase of cAMP concentration is prolonged by four successive injections of l-isoproterenol (15 30-minute intervals) the TH activity of intact and decentralized SCG is increased 48 hours later.l-Isoproterenol (four injections of 77 mumol/kg, each) and l-epinephrine (270 mumol/kg) fail to induce TH in the adrenal medulla. dl-Propranolol (125 mumol/kg i.p.) injected 30 minutes before l-isoproterenol blocks the increase of cAMP content and the delayed induction of TH activity in SCG. The elevation of TH activity elicited in SCG by beta adrenergic receptor agonists is always preceded by an increase of cAMP concentration lasting 90 minutes or longer. However, the induction of TH elicited by cold exposure or by reserpine administration can occur without an apparent increase in ganglionic cAMP concentration.", "contents": "Induction of tyrosine hydroxylase elicited by beta adrenergic receptor agonists in normal and decentralized sympathetic ganglia: role of cyclic 3',5' - adenosine monophosphate. A subcutaneous injection of an oil suspension of l-epinephrine (270 mumol/kg), dopamine (270 mumol/kg) or l-norepinephrine (270 mumol/kg), when administered with phenoxybenzamine (32 mumol/kg i.p.) to blocl alpha adrenergic effects, increases the cyclic 3', 5'-adenosine monophosphate (cAMP) content in superior cervical ganglia (SCG) of rats. The increase is highest after l-epinephrine and dopamine and is barely detectable after l-norepinephrine; it lasts longer than 2 hours after l-epinephrine, about 30 minutes after dopamine and is fleeting after l-norepinephrine. The duration of the increase in cAMP elicited by l-epinephrine in SCG of rats is dose-related. Furthermore, when the cAMP increase lasts longer than 90 minutes, 48 hours later the tyrosine hydroxylase (TH) activity in SCG is increased. l0Epinephrine (150 mol/kg s.c.) induces TH in decentralized ganglia. One injection of l-isoproterenol (77 mol/kg i.p.) increases cAMP concentrations in intact and decentralized SCG. This increase lasts only 30 minutes and fails to induce TH 48 hours later. However, if the increase of cAMP concentration is prolonged by four successive injections of l-isoproterenol (15 30-minute intervals) the TH activity of intact and decentralized SCG is increased 48 hours later.l-Isoproterenol (four injections of 77 mumol/kg, each) and l-epinephrine (270 mumol/kg) fail to induce TH in the adrenal medulla. dl-Propranolol (125 mumol/kg i.p.) injected 30 minutes before l-isoproterenol blocks the increase of cAMP content and the delayed induction of TH activity in SCG. The elevation of TH activity elicited in SCG by beta adrenergic receptor agonists is always preceded by an increase of cAMP concentration lasting 90 minutes or longer. However, the induction of TH elicited by cold exposure or by reserpine administration can occur without an apparent increase in ganglionic cAMP concentration."}
{"id": "PMID:237118", "title": "The distribution and movements of carbon dioxide, carbonic acid and bicarbonate between blood and milk in the goat.", "content": "1. A-V differences and milk concentrations of respiratory gases, pH, HCO3 and H2CO3 have been measured in lactating goats and cows. 2. The pH and [HCO3 minus] of milk were significantly lower than those of plasma while milk PCO2 was virtually identical to that of mammary venous blood. [H2CO3+ dissolved CO2] was similar in milk and blood. 3. 14-C (from injected [14-C]HCO3 minus was found to cross the mammary epithelium in both directions. 14-C also passed across the duct epithelium and since this epithelium has previously been shown to be impermeable to ions it is argued that 14-C crossed in an unionized form, i.e. as CO2 and/or H2CO3. 4. Hourly milking with the aid of oxytocin raised milk pH, [HCO3 minus], [H2CO3], [Na] and E1Cl], and lowered [K], [lactose] and [phosphate]. These effects are discussed in relation to the hypothesis proposed previously for the action of oxytocin on milk composition. 5. A scheme for the distribution and movements of CO2, H2CO3 and HCO3 minus between extracellular fluid and milk is suggested, and discussed in relation to Cl minus transport.", "contents": "The distribution and movements of carbon dioxide, carbonic acid and bicarbonate between blood and milk in the goat. 1. A-V differences and milk concentrations of respiratory gases, pH, HCO3 and H2CO3 have been measured in lactating goats and cows. 2. The pH and [HCO3 minus] of milk were significantly lower than those of plasma while milk PCO2 was virtually identical to that of mammary venous blood. [H2CO3+ dissolved CO2] was similar in milk and blood. 3. 14-C (from injected [14-C]HCO3 minus was found to cross the mammary epithelium in both directions. 14-C also passed across the duct epithelium and since this epithelium has previously been shown to be impermeable to ions it is argued that 14-C crossed in an unionized form, i.e. as CO2 and/or H2CO3. 4. Hourly milking with the aid of oxytocin raised milk pH, [HCO3 minus], [H2CO3], [Na] and E1Cl], and lowered [K], [lactose] and [phosphate]. These effects are discussed in relation to the hypothesis proposed previously for the action of oxytocin on milk composition. 5. A scheme for the distribution and movements of CO2, H2CO3 and HCO3 minus between extracellular fluid and milk is suggested, and discussed in relation to Cl minus transport."}
{"id": "PMID:237119", "title": "Lithium ions and the release of transmitter at the frog neuromuscular junction.", "content": "1. Transmitter release has been examined at the frog neuromuscular junction when all or part of the Na of the Ringer is replaced by Li ions. 2. No immediate change occurs in either the mean quantal content of the end-plate potential or the miniature end-plate potential frequency on changing to Li Ringer but over the following hour both these quantities increase by more than two orders of magnitude. 3. During thefirst 30-40 min of an exposure to Li-Ringer the m.e.p.p. frequency rises exponentially with a time constant of 10 min, and the mean quantal content of the e.p.p. grows by addition of extra evoked quanta, the increment rising exponentially with a time constant the same as that of the m.e.p.p. frequency. 4. Following this initial period in Li-Ringer the m. e.p.p. frequency accelerates to a peak of several hundred quanta per second and then declines slowly over the next few hours. Just before the m.e.p.p.frequency peak the conduction velocity of the presynaptic action potential declines and shortly afterwards synaptic transmission fails as the action potential no longer conducts into the terminals. 5. The rise in the m.e.p.p. frequency during the first 30-40 min is independent of the [Ca-2+]o. At subsequent times before the peak external Cabecomes progressively more effective in accelerating the m.e.p.p. frequency and in the presence of 1mM-EGTA spontaneous release stabilizes at 60-80 quanta/sec. 6. The [Li-+]o strongly influences the rate of increases in both evoked and spontaneous release but not their extent; replacing only half the Na of the Ringer by Li increases the time constants of the increases to about 30 min. 7. Rises in the m.e.p.p. frequency can be irreversibly accelerated by tetanizing the nerve in a Li-Ringer in which the Ca has been chelated by EGTA. The extent of the increases in the m.e.p.p. frequency is dependent on the number of pulses in the tetanus and is little affected by the frequency of stimulation. Accumulation of Li ions inside the presynaptic terminals probably underlies the changes in spontaneous release. 8. When only 10 percent of the Na of the Ringer is replaced by Li-+ ions the magnitude of post-tetanic potentiation of the e.p.p. and of the post-tetanic rise in the m.e.p.p. frequency is increased. Under these conditions changes in facilitation of the e.p.p. are small. 9. Various mechanisms by which Li could alter transmitter release are discussed and it is suggested that intracellular Ca sequestering mechanisms of the presynaptic terminals are affected when an end-plate is exposed to Li-Ringer.", "contents": "Lithium ions and the release of transmitter at the frog neuromuscular junction. 1. Transmitter release has been examined at the frog neuromuscular junction when all or part of the Na of the Ringer is replaced by Li ions. 2. No immediate change occurs in either the mean quantal content of the end-plate potential or the miniature end-plate potential frequency on changing to Li Ringer but over the following hour both these quantities increase by more than two orders of magnitude. 3. During thefirst 30-40 min of an exposure to Li-Ringer the m.e.p.p. frequency rises exponentially with a time constant of 10 min, and the mean quantal content of the e.p.p. grows by addition of extra evoked quanta, the increment rising exponentially with a time constant the same as that of the m.e.p.p. frequency. 4. Following this initial period in Li-Ringer the m. e.p.p. frequency accelerates to a peak of several hundred quanta per second and then declines slowly over the next few hours. Just before the m.e.p.p.frequency peak the conduction velocity of the presynaptic action potential declines and shortly afterwards synaptic transmission fails as the action potential no longer conducts into the terminals. 5. The rise in the m.e.p.p. frequency during the first 30-40 min is independent of the [Ca-2+]o. At subsequent times before the peak external Cabecomes progressively more effective in accelerating the m.e.p.p. frequency and in the presence of 1mM-EGTA spontaneous release stabilizes at 60-80 quanta/sec. 6. The [Li-+]o strongly influences the rate of increases in both evoked and spontaneous release but not their extent; replacing only half the Na of the Ringer by Li increases the time constants of the increases to about 30 min. 7. Rises in the m.e.p.p. frequency can be irreversibly accelerated by tetanizing the nerve in a Li-Ringer in which the Ca has been chelated by EGTA. The extent of the increases in the m.e.p.p. frequency is dependent on the number of pulses in the tetanus and is little affected by the frequency of stimulation. Accumulation of Li ions inside the presynaptic terminals probably underlies the changes in spontaneous release. 8. When only 10 percent of the Na of the Ringer is replaced by Li-+ ions the magnitude of post-tetanic potentiation of the e.p.p. and of the post-tetanic rise in the m.e.p.p. frequency is increased. Under these conditions changes in facilitation of the e.p.p. are small. 9. Various mechanisms by which Li could alter transmitter release are discussed and it is suggested that intracellular Ca sequestering mechanisms of the presynaptic terminals are affected when an end-plate is exposed to Li-Ringer."}
{"id": "PMID:237120", "title": "Chemical stimulatory mechanism in gastric secretion.", "content": "1. The serum gastrin level, gastric mucosal blood flow and acid secretion from the canine Heidenhain pouch have been measured in response to the introduction of bovine serum albumin, pepsin-digested albumin, an amino acid mixture, liver extract and mannitol used as control. 2. Distention of the Heidenhain pouch with mannitol or albumnin at pH 5-0 produced a similar pressure-related increase of acid secretion reaching a peak of only 10 percent of the maximal response to histamine. Pepsin-digested albumin was capable of producing larger acid outputs than undigested albumin. The highest acid output, attaining about 80 percent of the maximal response to histamine, was obtained with liver extract both before and after exhaustive dialysis to remove all the amino acids and short peptide fragments. An amino acid mixture containing all essential amino acids was also found to stimulate acid secretion but a lesser degree than liver extract. 3. This concluded that it is not the intact protein but the products of its digestion, the polypeptides and free amino acids, which are potent chemical stimulants of acid secretion from the oxyntic gland area. Since the serum gastrin level was not changed during acid secretion induced by peptic digests bathing the oxyntic gland area, the mechanism of chemical stimulation appears to be gastrin-independent. 4. The response to chemical stimulation by peptic digests can be greatly potentiated by combining this with distention of the oxyntic gland area. Topical application of xylocaine or atropine causes a marked decrease of Heidenhain pouch response to peptic digests, suggesting a possible neural reflex component in the mechanism of chemical stimulation of the oxyntic gland area. 5. When the pH of the liver extract in the Heidenhain pouch was gradually decreased in sequential order from 5-0 to 1-0, this resulted in a pH-related decrease in acid secretion and in the mucosal blood flow falling to the basal level at pH 1-0. Exogenous secretion given in graded doses from 0-5 to 8-0 u./kg. hr caused a small but dose-related inhibition of acid response to liver extract accompanied by a decrease of mucosal blood flow but without any significant change in the serum gastrin level. 6. The results indicate that the chemical stimulation of the oxyntic gland area by peptic digests is capable of inducing acid secretion by a local, gastrin-independent, partially neural reflex mechanism; sensitive to pH, pressure and secretin.", "contents": "Chemical stimulatory mechanism in gastric secretion. 1. The serum gastrin level, gastric mucosal blood flow and acid secretion from the canine Heidenhain pouch have been measured in response to the introduction of bovine serum albumin, pepsin-digested albumin, an amino acid mixture, liver extract and mannitol used as control. 2. Distention of the Heidenhain pouch with mannitol or albumnin at pH 5-0 produced a similar pressure-related increase of acid secretion reaching a peak of only 10 percent of the maximal response to histamine. Pepsin-digested albumin was capable of producing larger acid outputs than undigested albumin. The highest acid output, attaining about 80 percent of the maximal response to histamine, was obtained with liver extract both before and after exhaustive dialysis to remove all the amino acids and short peptide fragments. An amino acid mixture containing all essential amino acids was also found to stimulate acid secretion but a lesser degree than liver extract. 3. This concluded that it is not the intact protein but the products of its digestion, the polypeptides and free amino acids, which are potent chemical stimulants of acid secretion from the oxyntic gland area. Since the serum gastrin level was not changed during acid secretion induced by peptic digests bathing the oxyntic gland area, the mechanism of chemical stimulation appears to be gastrin-independent. 4. The response to chemical stimulation by peptic digests can be greatly potentiated by combining this with distention of the oxyntic gland area. Topical application of xylocaine or atropine causes a marked decrease of Heidenhain pouch response to peptic digests, suggesting a possible neural reflex component in the mechanism of chemical stimulation of the oxyntic gland area. 5. When the pH of the liver extract in the Heidenhain pouch was gradually decreased in sequential order from 5-0 to 1-0, this resulted in a pH-related decrease in acid secretion and in the mucosal blood flow falling to the basal level at pH 1-0. Exogenous secretion given in graded doses from 0-5 to 8-0 u./kg. hr caused a small but dose-related inhibition of acid response to liver extract accompanied by a decrease of mucosal blood flow but without any significant change in the serum gastrin level. 6. The results indicate that the chemical stimulation of the oxyntic gland area by peptic digests is capable of inducing acid secretion by a local, gastrin-independent, partially neural reflex mechanism; sensitive to pH, pressure and secretin."}
{"id": "PMID:237121", "title": "Molecular features of organic anion permeablity in ox red blood cell.", "content": "1. The penetration of organic anions into bovine red blood cells has been studied under experimental conditions where it could be distinguished from the penetration of undissociated acids which proceeds by diffusion through lipid zones of the membrane. 2. Several lines of evidence suggest that the entry of organic anions cannot be ascribed to simple diffusion across aqueous channels limited by positive charges but needs a specific interaction of the penetrating anion with a component of the membrane. 3. The structural requirements allowing for ionic transfer is a strong polar head for the smallest molecules and in addition an amphiphilic structure for acids with chain length greater than C4. Interaction between substrate and receptor requires at least a three point attachment involving three oxygen atoms in the substrate which react with complementary loci on the receptor to form ionic and hydrogen bonds. Such a three point attachment can be made by a sulphonic group or with carboxylic acid by alpha ketosubstitution, alpha hydroxysubstitution, addition of an amidegroup or addition of a second carboxyl group spatially close to the first. 4. As suggested by the behaviour of the formate anion, in such a transport system any carboxylic acid could interact transiently with the receptor and therefore interfere with the transport of an organic anion even though such ionic interaction with the receptor were insufficient to produce transport of the acid itself.", "contents": "Molecular features of organic anion permeablity in ox red blood cell. 1. The penetration of organic anions into bovine red blood cells has been studied under experimental conditions where it could be distinguished from the penetration of undissociated acids which proceeds by diffusion through lipid zones of the membrane. 2. Several lines of evidence suggest that the entry of organic anions cannot be ascribed to simple diffusion across aqueous channels limited by positive charges but needs a specific interaction of the penetrating anion with a component of the membrane. 3. The structural requirements allowing for ionic transfer is a strong polar head for the smallest molecules and in addition an amphiphilic structure for acids with chain length greater than C4. Interaction between substrate and receptor requires at least a three point attachment involving three oxygen atoms in the substrate which react with complementary loci on the receptor to form ionic and hydrogen bonds. Such a three point attachment can be made by a sulphonic group or with carboxylic acid by alpha ketosubstitution, alpha hydroxysubstitution, addition of an amidegroup or addition of a second carboxyl group spatially close to the first. 4. As suggested by the behaviour of the formate anion, in such a transport system any carboxylic acid could interact transiently with the receptor and therefore interfere with the transport of an organic anion even though such ionic interaction with the receptor were insufficient to produce transport of the acid itself."}
{"id": "PMID:237122", "title": "Effects of lysergic acid diethylamide on autonomic post-ganglionic transmission.", "content": "1. Six sites of autonomic post-ganglionic transmission were examined for susceptibility to LSD. Inhibition of transmission by LSD was confined to the three sympathetic junctions. 2. Inhibition of sympathetic transmission was maximal with short trains of pulses and declined considerably as train length was increased. 3. Evidence for a presynaptic mode of action was obtained. This was the predominant effect of LSD in the rat anococcygeus and dog retractor penis because alpha-adrenoceptor-blocking properties were feeble or absent; but in dog splenic strips LSD produced marked post-synaptic alpha-blockade. 4. The presynaptic inhibitory effect of LSD was unrelated to its 5-hydroxytryptamine-blocking property because it was not shared by methysergide. Neither was it mediated by prostaglandin release because it was unaltered by indomethacin, which suppresses prostaglandin synthesis. 5. In the rat anococcygeus and dog retractor penis larger doses of LSD induced slow contractions and, as a result of the concurrent block of motor transmission, revealed relaxation responses on transmural stimulation, caused by the excitation of sacral inhibitory fibres present in these muscles. 6. The LSD contractions were due to stimulation of post-synaptic alpha-adrenoceptors because they were abolished by phentolamine or yohimbine but were present as usual in preparations taken from reserpinized animals. 7. LSD blocked presynaptic alpha-adrenoceptors in the cholinergic motor fibres to the longitudinal muscle of the guinea-pig ileum.", "contents": "Effects of lysergic acid diethylamide on autonomic post-ganglionic transmission. 1. Six sites of autonomic post-ganglionic transmission were examined for susceptibility to LSD. Inhibition of transmission by LSD was confined to the three sympathetic junctions. 2. Inhibition of sympathetic transmission was maximal with short trains of pulses and declined considerably as train length was increased. 3. Evidence for a presynaptic mode of action was obtained. This was the predominant effect of LSD in the rat anococcygeus and dog retractor penis because alpha-adrenoceptor-blocking properties were feeble or absent; but in dog splenic strips LSD produced marked post-synaptic alpha-blockade. 4. The presynaptic inhibitory effect of LSD was unrelated to its 5-hydroxytryptamine-blocking property because it was not shared by methysergide. Neither was it mediated by prostaglandin release because it was unaltered by indomethacin, which suppresses prostaglandin synthesis. 5. In the rat anococcygeus and dog retractor penis larger doses of LSD induced slow contractions and, as a result of the concurrent block of motor transmission, revealed relaxation responses on transmural stimulation, caused by the excitation of sacral inhibitory fibres present in these muscles. 6. The LSD contractions were due to stimulation of post-synaptic alpha-adrenoceptors because they were abolished by phentolamine or yohimbine but were present as usual in preparations taken from reserpinized animals. 7. LSD blocked presynaptic alpha-adrenoceptors in the cholinergic motor fibres to the longitudinal muscle of the guinea-pig ileum."}
{"id": "PMID:237125", "title": "Etonitazene. An improved synthesis.", "content": "1-(BETA-Kiethylaminoethyl)-2-(p-ethoxybenzyl)-5-nitrobenzimidazole (u, etonitazene) is a potent analgesic that has value in drug addiction studies. We have developed a simple high-yield synthesis of 1 that is adaptable to alrge scale preparations. The synthesis involves the condensation of 2-(beta-diethylaminoethylamino)-5-mitroaniline and p-ethoxyphenylacetic acid in Thf in the presence of EEDQ.", "contents": "Etonitazene. An improved synthesis. 1-(BETA-Kiethylaminoethyl)-2-(p-ethoxybenzyl)-5-nitrobenzimidazole (u, etonitazene) is a potent analgesic that has value in drug addiction studies. We have developed a simple high-yield synthesis of 1 that is adaptable to alrge scale preparations. The synthesis involves the condensation of 2-(beta-diethylaminoethylamino)-5-mitroaniline and p-ethoxyphenylacetic acid in Thf in the presence of EEDQ."}
{"id": "PMID:237126", "title": "Comparison of male and female physician's associate program applicants.", "content": "Using personality measures, the author examined Physician's Associate Program applicants at the Duke University School of Medicine, comparing male and female applicants and the outcome for these applicants in terms of acceptance into paramedical training. The perecentage of women accepted into training was similar to the percentage who applied for training. However, women invited for interview were more aggressive, autonomous, impulsive, playful, and flexible than the males invited to interview, suggesting self-selection by women in applying for paramedical training. Women accepted for training were more \"feminine\" in the conventional sense, and bias against female applicants less accepting of social mores and the traditional female role was revealed. The implications of these findings are discussed.", "contents": "Comparison of male and female physician's associate program applicants. Using personality measures, the author examined Physician's Associate Program applicants at the Duke University School of Medicine, comparing male and female applicants and the outcome for these applicants in terms of acceptance into paramedical training. The perecentage of women accepted into training was similar to the percentage who applied for training. However, women invited for interview were more aggressive, autonomous, impulsive, playful, and flexible than the males invited to interview, suggesting self-selection by women in applying for paramedical training. Women accepted for training were more \"feminine\" in the conventional sense, and bias against female applicants less accepting of social mores and the traditional female role was revealed. The implications of these findings are discussed."}
{"id": "PMID:237133", "title": "Some aspects of proximal tubular sodium chloride reabsorption in Necturus kidney.", "content": "Some aspects of proximal tubular sodium chloride reabsorption in Necturus kidney. Renal tubular reabsorption of fluid and sodium was measured by clearance methods in the doubly perfused Necturus kidney in which the bicarbonate concentration was varied between 0 and 60 mEq/liter. The effects of Damox (2.2 times 10-3M), ocubain (10-5M) and ethacrynic acid (10-4M) and of acidosis were also investigated. In addition to clearance experiments, stationary microperfusion experiments were carried out on promimal tubules to measure volume flow and steady-state sodium and chloride concentration differences across the tubular epithelium. In some experiments, the transepithelial electrical potential difference was also measured using an axial electrode system. The following results were obtained: 1) Bicarbonate is not essential to the operation of renal tubular fluid and sodium transport. 2) Total renal and proximal tubular fluid and sodium transport are partially inhibited by Diamox, ouabian and ethacrynic acid. 3) The proximal tubule maintains a significant transepithelial sodium and chloride concentration difference and a significant electrical potential difference (lumen-negative) in the presence of a poorly permeant nonelectrolyte. The direction and magnitude of the electrical polarization fully accounts for the observed chloride concentration difference. The data support the thesis that sodium chloride transport accross the proximal tubular epithelium takes place by active sodium transport and electically coupled passive chloride reabsorption. Important species differences with respect to mammalian transport mechanisms are discussed.", "contents": "Some aspects of proximal tubular sodium chloride reabsorption in Necturus kidney. Some aspects of proximal tubular sodium chloride reabsorption in Necturus kidney. Renal tubular reabsorption of fluid and sodium was measured by clearance methods in the doubly perfused Necturus kidney in which the bicarbonate concentration was varied between 0 and 60 mEq/liter. The effects of Damox (2.2 times 10-3M), ocubain (10-5M) and ethacrynic acid (10-4M) and of acidosis were also investigated. In addition to clearance experiments, stationary microperfusion experiments were carried out on promimal tubules to measure volume flow and steady-state sodium and chloride concentration differences across the tubular epithelium. In some experiments, the transepithelial electrical potential difference was also measured using an axial electrode system. The following results were obtained: 1) Bicarbonate is not essential to the operation of renal tubular fluid and sodium transport. 2) Total renal and proximal tubular fluid and sodium transport are partially inhibited by Diamox, ouabian and ethacrynic acid. 3) The proximal tubule maintains a significant transepithelial sodium and chloride concentration difference and a significant electrical potential difference (lumen-negative) in the presence of a poorly permeant nonelectrolyte. The direction and magnitude of the electrical polarization fully accounts for the observed chloride concentration difference. The data support the thesis that sodium chloride transport accross the proximal tubular epithelium takes place by active sodium transport and electically coupled passive chloride reabsorption. Important species differences with respect to mammalian transport mechanisms are discussed."}
{"id": "PMID:237134", "title": "Nature of the acidifying defect after the relief of ureteral obstruction.", "content": "Nature of the acidifying defect observed after relief of ureteral obstruction. The acidifying capacity of the normal and experimental kidney was studied in rats three hours after release of complete unilateral ureteral obstruction or after unilateral release of unilateral ureteral obstruction,  mean plasma bicarbonate concentration was 23.5 mEq/liter, and plasma pH, 7.45. Urine pH from the postreleased kidney was 7.47 and 6.01 from the control side. Net acid escretion averaged 0.97 muEq/min in the experimental kidney. Fractional excretion of bicarbonate averaged 0.02% in the control and 3.17% in the experimental kidney. In eight animals with unilateral release of bilateral ureteral obstruction, mean plasma bicarbonate was 16.9 mEq/min and plasma pH was7.35. Mean urine pH in the postreleased Kidney was 6.11, net acid excretion averaged 2.01 plus or minus 0.69 muEq/min and fractional bicarbonate excretion averaged 0.84%.", "contents": "Nature of the acidifying defect after the relief of ureteral obstruction. Nature of the acidifying defect observed after relief of ureteral obstruction. The acidifying capacity of the normal and experimental kidney was studied in rats three hours after release of complete unilateral ureteral obstruction or after unilateral release of unilateral ureteral obstruction,  mean plasma bicarbonate concentration was 23.5 mEq/liter, and plasma pH, 7.45. Urine pH from the postreleased kidney was 7.47 and 6.01 from the control side. Net acid escretion averaged 0.97 muEq/min in the experimental kidney. Fractional excretion of bicarbonate averaged 0.02% in the control and 3.17% in the experimental kidney. In eight animals with unilateral release of bilateral ureteral obstruction, mean plasma bicarbonate was 16.9 mEq/min and plasma pH was7.35. Mean urine pH in the postreleased Kidney was 6.11, net acid excretion averaged 2.01 plus or minus 0.69 muEq/min and fractional bicarbonate excretion averaged 0.84%."}
{"id": "PMID:237135", "title": "Renal mitochondrial glutamine metabolism and dietary potassium and protein content.", "content": "Renal mitochondrial glutamine metabolism and dietary potassium and protein content. Glutamine distribution, glutamate accumulation, phosphate-dependent glutaminase (PDG) concentrations and intact mitochondrial ammonia production were studied in renal mitochondria from rats fed low, normal and high potassium diets and in mitochondria from rats fed high or low protein diets. The rats given a low potassium diet were potassium-depleted by 10 to 20% but in none of the groups were there any abnormalities of extracellular acid-base status. Glutamine was present in the outer space of mitochondria but could not be depleted in the matrix space in any group. In both the potassium-depleted and the high protein animals, we found increased matrix -14-C-uptake of glutamine (as -14-C-glutamate), increased intact mitochondrial ammonia production and increased concentrations of PDG. In the K+-depleted group there was a decreased matrix -14C-uptake when -14C-gamma-ketoglutarate of -14C-glutamate was present in the medium. Potassium loading produced no change in mitochondrial glutamine metabolism. Protein loading (compared with protein depletion) and potassium depletion induce an increased uptake of glutamine into the renal mitochondrial matrix space which leads to its increased deamidation. This adaption may explain the increased renal ammonia production seen in these situations when compared to their respective controls.", "contents": "Renal mitochondrial glutamine metabolism and dietary potassium and protein content. Renal mitochondrial glutamine metabolism and dietary potassium and protein content. Glutamine distribution, glutamate accumulation, phosphate-dependent glutaminase (PDG) concentrations and intact mitochondrial ammonia production were studied in renal mitochondria from rats fed low, normal and high potassium diets and in mitochondria from rats fed high or low protein diets. The rats given a low potassium diet were potassium-depleted by 10 to 20% but in none of the groups were there any abnormalities of extracellular acid-base status. Glutamine was present in the outer space of mitochondria but could not be depleted in the matrix space in any group. In both the potassium-depleted and the high protein animals, we found increased matrix -14-C-uptake of glutamine (as -14-C-glutamate), increased intact mitochondrial ammonia production and increased concentrations of PDG. In the K+-depleted group there was a decreased matrix -14C-uptake when -14C-gamma-ketoglutarate of -14C-glutamate was present in the medium. Potassium loading produced no change in mitochondrial glutamine metabolism. Protein loading (compared with protein depletion) and potassium depletion induce an increased uptake of glutamine into the renal mitochondrial matrix space which leads to its increased deamidation. This adaption may explain the increased renal ammonia production seen in these situations when compared to their respective controls."}
{"id": "PMID:237143", "title": "Arterial blood gas tensions and acid-base status of Wistar rats during thiopental and halothane anesthesia.", "content": "Arterial blood gas tensions and acid-base status of spontaneously-breathing, unanesthetized Wister rats were compared with values obtained during 4 hr of thiopental and 6 hr of halothane (1%) anesthesia. During thiopental anesthesia, marked respiratory depression occurred (PaCO-2:57.0 plus or minus 10.0 MM Hg, PaO-2:70.4 plus or minus 11.2 MM Hg). Thirty-six percent of the rats died. During inhalation of room air and 1% halothane, PaO-2 decreased also, whereas PaO-2 did not change. Twenty-seven percent of the original number of rats died. Lowered arterial oxygen tension may have caused death; no rats died during inhalation of oxygen and 1% halothane. This technic insured sufficient analgesia for surgical procedures without marked alterations of the acid base status and is recommended for long-term anesthesia of small laboratory animals like rats.", "contents": "Arterial blood gas tensions and acid-base status of Wistar rats during thiopental and halothane anesthesia. Arterial blood gas tensions and acid-base status of spontaneously-breathing, unanesthetized Wister rats were compared with values obtained during 4 hr of thiopental and 6 hr of halothane (1%) anesthesia. During thiopental anesthesia, marked respiratory depression occurred (PaCO-2:57.0 plus or minus 10.0 MM Hg, PaO-2:70.4 plus or minus 11.2 MM Hg). Thirty-six percent of the rats died. During inhalation of room air and 1% halothane, PaO-2 decreased also, whereas PaO-2 did not change. Twenty-seven percent of the original number of rats died. Lowered arterial oxygen tension may have caused death; no rats died during inhalation of oxygen and 1% halothane. This technic insured sufficient analgesia for surgical procedures without marked alterations of the acid base status and is recommended for long-term anesthesia of small laboratory animals like rats."}
{"id": "PMID:237150", "title": "[Loading-stable osteosynthesis of pertrochanteric femoral fractures using a condyle plate].", "content": "Also the authors' Department shares SPIER's opinion, according to which the ideal treatment of the proximal femur fractures is the osteosynthesis, with the greatest stability. The aim of surgical treatment of the fracture is the motion-stable and possibly loading-stable osteosynthesis. Since proximal femur fractures occur mostly in aged patients, the survival is considerably augmented by early and efficacious mobilization. If the general state of the patient is suitable, after consultation with the anaesthesiologist and the internist the surgical intervention is carried out. AO-condyle-plate yields further possibility to the loading-stable osteosynthesis of the pertrochanteric fractures.", "contents": "[Loading-stable osteosynthesis of pertrochanteric femoral fractures using a condyle plate]. Also the authors' Department shares SPIER's opinion, according to which the ideal treatment of the proximal femur fractures is the osteosynthesis, with the greatest stability. The aim of surgical treatment of the fracture is the motion-stable and possibly loading-stable osteosynthesis. Since proximal femur fractures occur mostly in aged patients, the survival is considerably augmented by early and efficacious mobilization. If the general state of the patient is suitable, after consultation with the anaesthesiologist and the internist the surgical intervention is carried out. AO-condyle-plate yields further possibility to the loading-stable osteosynthesis of the pertrochanteric fractures."}
{"id": "PMID:237151", "title": "[Comparative evaluation of various surgical technics in the treatment of dislocated patellar fractures].", "content": "From the point of view of the different operative methods 137 patellar fractures operated on in the 3 years' material (1969--1971) of the Central Casualty Rehabilitation Institute have been analysed by the authors. 116 fractures could be re-examined 2--4 years after patients were back at work. If the operation was followed by adequate functional management, satisfactory results were found after all operations. When the patients were back at work, further improvement of the results has been observed. In the time the patients got again to work, the results of partial patellectomy seemed better,--however, after 2--4 years osteosynthesis yielded better final results. Traction loop proved more effective than cerclage. If possible, conservation and exact unionof the patella is of great importance in both juveniles and manual workers. Early functional treatment improves the late results of the operation.", "contents": "[Comparative evaluation of various surgical technics in the treatment of dislocated patellar fractures]. From the point of view of the different operative methods 137 patellar fractures operated on in the 3 years' material (1969--1971) of the Central Casualty Rehabilitation Institute have been analysed by the authors. 116 fractures could be re-examined 2--4 years after patients were back at work. If the operation was followed by adequate functional management, satisfactory results were found after all operations. When the patients were back at work, further improvement of the results has been observed. In the time the patients got again to work, the results of partial patellectomy seemed better,--however, after 2--4 years osteosynthesis yielded better final results. Traction loop proved more effective than cerclage. If possible, conservation and exact unionof the patella is of great importance in both juveniles and manual workers. Early functional treatment improves the late results of the operation."}
{"id": "PMID:237152", "title": "[History of traumatology in Hungary].", "content": "The history of the Hungarian Traumatology since the 16th century up to the present days is outlined by the author. The most important works--dealing with the treatment of the fractures and with the activity of other areas of the traumatology--are enumerated. Moreover, the factors promoting the development of the Hungarian traumatology are specified and the important surgeons active in the field of traumatology and the war operative surgery are named, who too have contributed to the development of the Hungarian traumatology. The importance of the Hungarian Institute of Traumatology--founded in 1956--is emphasized,--thus, the traumatology became an independent section of the Hungarian public health; and centrally directed and organized function of the traumatology was assured.", "contents": "[History of traumatology in Hungary]. The history of the Hungarian Traumatology since the 16th century up to the present days is outlined by the author. The most important works--dealing with the treatment of the fractures and with the activity of other areas of the traumatology--are enumerated. Moreover, the factors promoting the development of the Hungarian traumatology are specified and the important surgeons active in the field of traumatology and the war operative surgery are named, who too have contributed to the development of the Hungarian traumatology. The importance of the Hungarian Institute of Traumatology--founded in 1956--is emphasized,--thus, the traumatology became an independent section of the Hungarian public health; and centrally directed and organized function of the traumatology was assured."}
{"id": "PMID:237154", "title": "[Bilateral shortening of the m. rectus femoris due to complications after injection].", "content": "A case of bilateral shortening of the muscle rectus femoris--developed as complication of the injection--is reported. The mechanisms of the development of the alteration and the examination method are described. The possibility of the prevention of the extension knee constractures--developing as complication of the injection--is similarly discussed.", "contents": "[Bilateral shortening of the m. rectus femoris due to complications after injection]. A case of bilateral shortening of the muscle rectus femoris--developed as complication of the injection--is reported. The mechanisms of the development of the alteration and the examination method are described. The possibility of the prevention of the extension knee constractures--developing as complication of the injection--is similarly discussed."}
{"id": "PMID:237157", "title": "[Current problems in the treatment of open fractures].", "content": "The paper evidently does not discuss several important problems of the management of open fractures, but it is confined to the exposition of some fundamental rules of their traitment. Nowadays, the treatment of open fractures is to be decided individually for all cases. A great number of patients with open fracture owe their recovery to the proper first aid care at scence of accident. This is also in respect of the further treatment in the hospital of great importance. Exagerated activity is usually superfluous in the treatment of open fractures. Less and more proper management is often more useful for the injured patient.", "contents": "[Current problems in the treatment of open fractures]. The paper evidently does not discuss several important problems of the management of open fractures, but it is confined to the exposition of some fundamental rules of their traitment. Nowadays, the treatment of open fractures is to be decided individually for all cases. A great number of patients with open fracture owe their recovery to the proper first aid care at scence of accident. This is also in respect of the further treatment in the hospital of great importance. Exagerated activity is usually superfluous in the treatment of open fractures. Less and more proper management is often more useful for the injured patient."}
{"id": "PMID:237158", "title": "[Classification of 557 open fractures of the leg and results of the treatment].", "content": "The results of the treatment of 557 open fractures of the leg are discussed from the standpoint of healing of the fractures. According to the severity of the fracture the patients have been ranked into 3 groups. Although in 95,1% of the patients recovery was obtained, in 50% of severe injuries healing occurred only over 20 weeks. The time of recovery was influenced unfavourably by the non stable osteosyntheses. Conservative treatment performed in a great number of patients yielded satisfactory results. The number of the cases treated with stable osteosynthesis is relatively small for comparison with the former groups. In the authors' opinion, the classification of the cases according to the severity of the fracture is of great importance, since it influences the treatment, the recovery time as well as the prognosis.", "contents": "[Classification of 557 open fractures of the leg and results of the treatment]. The results of the treatment of 557 open fractures of the leg are discussed from the standpoint of healing of the fractures. According to the severity of the fracture the patients have been ranked into 3 groups. Although in 95,1% of the patients recovery was obtained, in 50% of severe injuries healing occurred only over 20 weeks. The time of recovery was influenced unfavourably by the non stable osteosyntheses. Conservative treatment performed in a great number of patients yielded satisfactory results. The number of the cases treated with stable osteosynthesis is relatively small for comparison with the former groups. In the authors' opinion, the classification of the cases according to the severity of the fracture is of great importance, since it influences the treatment, the recovery time as well as the prognosis."}
{"id": "PMID:237159", "title": "[Infectious complications of 227 open fractures of the leg].", "content": "Out of 557 open fractures of the leg we have analysed 472 cases in respect of recovery. We tried to discrive the relationship between the infection and the severity of the lesion and the methods of treatment resp. We have analysed also the further course of the infect.on. In our material considerable risk of the infections in the case of open leg fractures was found, since the incidence of all infections corresponded--in accordance with the data of the literature--to 16,7% of the appreciable cases. Significant relationship between the occurrence of infections and the severity of the lesion was found. In the material analysed according to the ACD code the incidence of infections is in the severely injured patients three times as much as in the case of slight or moderately severe groups. The occurrence of posttraumatic osteitis corresponds to 9,11%--this latter is similarly in relation with the severity of the lesion. The infection leads to the protraction of the osseous union,--however, no convincing data were found in the authors' material in respect of the relationship between the infection and the methods of treatment. The course and the proportion of healing of the infected cases correspond to the mean values reported in the literature. On the basis of their great material it is stated by the authors that only in the case of lesions with identical or at the least  similar severity comparison of the results of recovery or of the complications is possible and suitable.", "contents": "[Infectious complications of 227 open fractures of the leg]. Out of 557 open fractures of the leg we have analysed 472 cases in respect of recovery. We tried to discrive the relationship between the infection and the severity of the lesion and the methods of treatment resp. We have analysed also the further course of the infect.on. In our material considerable risk of the infections in the case of open leg fractures was found, since the incidence of all infections corresponded--in accordance with the data of the literature--to 16,7% of the appreciable cases. Significant relationship between the occurrence of infections and the severity of the lesion was found. In the material analysed according to the ACD code the incidence of infections is in the severely injured patients three times as much as in the case of slight or moderately severe groups. The occurrence of posttraumatic osteitis corresponds to 9,11%--this latter is similarly in relation with the severity of the lesion. The infection leads to the protraction of the osseous union,--however, no convincing data were found in the authors' material in respect of the relationship between the infection and the methods of treatment. The course and the proportion of healing of the infected cases correspond to the mean values reported in the literature. On the basis of their great material it is stated by the authors that only in the case of lesions with identical or at the least  similar severity comparison of the results of recovery or of the complications is possible and suitable."}
{"id": "PMID:237169", "title": "Constituents of Ruscus aculeatus.", "content": "A phytochemical investigation of the acidic fraction from an ethanolic extract of the roots of Ruscus aculeatus L. (Liliaceae) has resulted in the isolation and identification of a sterol mixture, a fatty acid mixture, chrysophanic acid, a new compound named euparone and an incompletely characterized phenolic substance.", "contents": "Constituents of Ruscus aculeatus. A phytochemical investigation of the acidic fraction from an ethanolic extract of the roots of Ruscus aculeatus L. (Liliaceae) has resulted in the isolation and identification of a sterol mixture, a fatty acid mixture, chrysophanic acid, a new compound named euparone and an incompletely characterized phenolic substance."}
{"id": "PMID:237234", "title": "Medical and surgical management of reflux esophagitis.  A 38-month report of a prospective clinical trial.", "content": "We compared the surgical and medical managements of reflux esophagitis in a prospective managements of reflux esophagitis in a prospective clinical trial.  Patients wissigned to surgical (15 patients) and medical (16 patients) groups.  A non-randomized medical group (20 patients) was also studied.  Seventy three per cent of the surgical and 19 per cent of the medical group had an excellent to good response.  A fair to poor response was observed in 81 per cent of medical and 27 per cent of surgical patients.  Symptomatic improvement was accompanied by normal findings on acid infusion test and esophagoscopy.  The histologic appearance of the squamous mucosa, however, remained abnormal in all but one patient.  In patients who did well after operation there was improvement in resting lower-esophageal-sphincter pressures and absence of gastroesophageal reflux.  The relative increases in pphincter pressure to graded increases in gastric pressure, however, remained abnormal in all but one patient.", "contents": "Medical and surgical management of reflux esophagitis.  A 38-month report of a prospective clinical trial. We compared the surgical and medical managements of reflux esophagitis in a prospective managements of reflux esophagitis in a prospective clinical trial.  Patients wissigned to surgical (15 patients) and medical (16 patients) groups.  A non-randomized medical group (20 patients) was also studied.  Seventy three per cent of the surgical and 19 per cent of the medical group had an excellent to good response.  A fair to poor response was observed in 81 per cent of medical and 27 per cent of surgical patients.  Symptomatic improvement was accompanied by normal findings on acid infusion test and esophagoscopy.  The histologic appearance of the squamous mucosa, however, remained abnormal in all but one patient.  In patients who did well after operation there was improvement in resting lower-esophageal-sphincter pressures and absence of gastroesophageal reflux.  The relative increases in pphincter pressure to graded increases in gastric pressure, however, remained abnormal in all but one patient."}
{"id": "PMID:237241", "title": "The effect of chronic ammonium chloride ingestion on parathyroid hormone function.", "content": "The purpose of this study was to examine the effect of ammonium chloride ingestion on the hypercalcemic effect of parathyroid hormone in vivo. Thyroparathyroidectomized rats were given 1.5% ammonium chloride for 5-6 days. Ingestion of ammonium chloride increased serum calcium, but also significantly enhanced the calcium elevating effect of injected parathyroid extract. This result is compatible with a proposed hypothesis that the calcium mobilizing function of the parathyroid hormone may be enhanced by the hormone's own influence on systemic hydrogen ion concentration.", "contents": "The effect of chronic ammonium chloride ingestion on parathyroid hormone function. The purpose of this study was to examine the effect of ammonium chloride ingestion on the hypercalcemic effect of parathyroid hormone in vivo. Thyroparathyroidectomized rats were given 1.5% ammonium chloride for 5-6 days. Ingestion of ammonium chloride increased serum calcium, but also significantly enhanced the calcium elevating effect of injected parathyroid extract. This result is compatible with a proposed hypothesis that the calcium mobilizing function of the parathyroid hormone may be enhanced by the hormone's own influence on systemic hydrogen ion concentration."}
{"id": "PMID:237248", "title": "Drug overdoses: Is one stomach washing enough?", "content": "Naso-gastric tube aspirates were taken from patients with drug overdoses who had been given a gastric lavage and admitted to the resuscitation ward. Although care was taken to conduct thorough washouts, it was found that these were not always efficient. In several cases an amount equivalent to a therapeutic dose of drug was recovered in later aspirates. There was no correlation between the amount of drug recovered in the initial stomach washings and that found in the aspirates. It was concluded that routine aspiration of gastric contents at hourly intervals after admission was of considerable value in removing any residual drugs.", "contents": "Drug overdoses: Is one stomach washing enough? Naso-gastric tube aspirates were taken from patients with drug overdoses who had been given a gastric lavage and admitted to the resuscitation ward. Although care was taken to conduct thorough washouts, it was found that these were not always efficient. In several cases an amount equivalent to a therapeutic dose of drug was recovered in later aspirates. There was no correlation between the amount of drug recovered in the initial stomach washings and that found in the aspirates. It was concluded that routine aspiration of gastric contents at hourly intervals after admission was of considerable value in removing any residual drugs."}
{"id": "PMID:237252", "title": "Edema of the pulmonary interstitium in infants and children.", "content": "Ten infants and children with respiratory failure, receiving standard maintenance water requirements, were treated on 13 occasions with intravenously given furosemide (1 to 2 mg/kg) because of continued impairment of oxygenation despite conventional therapy. Pulmonary auscultation and radiographs were normal or typical of the primary diagnosis. After a five-fold increase in urine output the mean Po2 rose from 61 mm Hg at a mean FiO2 of 0.7 to 140 mm Hg at an FiO2 of 0.65. The Pco2 decreased from 46 to 38 mm Hg. Interstitial pulmonary edema in these patients can be related to both their lung disease and impaired water tolerance during ventilatory therapy.", "contents": "Edema of the pulmonary interstitium in infants and children. Ten infants and children with respiratory failure, receiving standard maintenance water requirements, were treated on 13 occasions with intravenously given furosemide (1 to 2 mg/kg) because of continued impairment of oxygenation despite conventional therapy. Pulmonary auscultation and radiographs were normal or typical of the primary diagnosis. After a five-fold increase in urine output the mean Po2 rose from 61 mm Hg at a mean FiO2 of 0.7 to 140 mm Hg at an FiO2 of 0.65. The Pco2 decreased from 46 to 38 mm Hg. Interstitial pulmonary edema in these patients can be related to both their lung disease and impaired water tolerance during ventilatory therapy."}
{"id": "PMID:237253", "title": "The muscular membrane and calcium activation of the contractile system of a lamellibranch smooth muscle (ABRM).", "content": "1. Thin bundles of fresh ABRM treated by EDTA solution or Triton x-100 0.1% can be brought like glycerol-extracted fibres through contraction-relaxation cycles by changing the free Ca2+ level of the bathing medium for 10-6 M to 10-9 M. The kinetics of isometric force development and relaxation has been studied in the two conditions i.e ionic strength 0.06 pH 6.5 and ionic strength 0.28, pH 7.0 which are known to induce the catch-state in glycerol extracted fibres. When the low Ca-2+ solution (10-9M) is substituted for the high Ca-2+ solution (10-6M) immediately after the maximal force has been developed, relaxation occurs at a higher rate at ionic strength 0928 and pH 6.5. In this last condition, no tension redevelops after a quick release applied during the slow relaxation. 2. During the plateau, in presence of Ca-2+ 10-6 M. a quick release applied at any time is followed by a large redevelopment of tension at ionic strength 0.06 and pH 6.5. At ionic strength 0.28 and pH 7.0, the tension redevelops only during the decreased from 10-6 to 10-9 M without any change in the time course of the tension maintained. 3. These results suggest that in EDTA and Triton X-100 treated fibres of Abrm, the catch-state is spontaneously induced after the activation of the contractile mechanism under the same conditions of ionic strengh and pH as in glycerol extracted fibres. However, in the EDTA and Triton treated fibres, the presence of a high free Ca-2+ level is not necessary to maintain the tension in the catch-state induced at ionic strength 0.28 and pH 7.0.", "contents": "The muscular membrane and calcium activation of the contractile system of a lamellibranch smooth muscle (ABRM). 1. Thin bundles of fresh ABRM treated by EDTA solution or Triton x-100 0.1% can be brought like glycerol-extracted fibres through contraction-relaxation cycles by changing the free Ca2+ level of the bathing medium for 10-6 M to 10-9 M. The kinetics of isometric force development and relaxation has been studied in the two conditions i.e ionic strength 0.06 pH 6.5 and ionic strength 0.28, pH 7.0 which are known to induce the catch-state in glycerol extracted fibres. When the low Ca-2+ solution (10-9M) is substituted for the high Ca-2+ solution (10-6M) immediately after the maximal force has been developed, relaxation occurs at a higher rate at ionic strength 0928 and pH 6.5. In this last condition, no tension redevelops after a quick release applied during the slow relaxation. 2. During the plateau, in presence of Ca-2+ 10-6 M. a quick release applied at any time is followed by a large redevelopment of tension at ionic strength 0.06 and pH 6.5. At ionic strength 0.28 and pH 7.0, the tension redevelops only during the decreased from 10-6 to 10-9 M without any change in the time course of the tension maintained. 3. These results suggest that in EDTA and Triton X-100 treated fibres of Abrm, the catch-state is spontaneously induced after the activation of the contractile mechanism under the same conditions of ionic strengh and pH as in glycerol extracted fibres. However, in the EDTA and Triton treated fibres, the presence of a high free Ca-2+ level is not necessary to maintain the tension in the catch-state induced at ionic strength 0.28 and pH 7.0."}
{"id": "PMID:237254", "title": "The control mechanism of relaxation in molluscan catch-muscle (ABRM).", "content": "The relaxing effects of 5-hydroxytryptamine (5-HT) have been tested on glycerol-extracted and chemically treated fibres (EDTA and Triton X-100 at two ionic strengths (0.06 and 0.28) and two pH's (6.5 and 7.0). The resistance to stretch of the two muscle preparations has been studied in the low Ca2+ medium i.e. without contractile activity in presence and in absence of 5-HT. The presence of 5-HT reduces significantly the resistance to stretch of chemically treated fibers in conditions of ionic strength 0.28 and 7.0, but has no effect on glycerol extracted fibres. 2. After the maximal tension has been developed in a high Ca2+ solution (10-6 M) the rate of relaxation of chemically treated fibres, induced by a low Ca2+ solution (10-9 M) at ionic strength 0.28 and pH 7.0 is increased by the addition of 5-HT. No effect is observed in glycerol extreacted fibres. 3. Chemically treated fibres in catch-state induced at ionic strength 0.28 and pH 6.5. 4. Cyclic AMP (c-AMP) induces the same relaxing effects at 5-HT on chemically treated fibres in the same conditions of ionic strength, pH and Ca2+ concentration. 5. The results are in disagreement with the hypothesis that the catch-state in ABRM is due to a lowering of the intracellular strength and pH; they suggest that the intracellular physiological conditions are rather near ionic strength 0.28 and pH 7.0 even in catch-state. We suppose that the relaxing effect of 5-HT, is not be due to a decrease of the intracellular free Ca2+ level but rather to an increase of the rate of Ca2+ release from the contractile proteins, and that it is mediated through c-AMP and intracellular relaxing mediator.", "contents": "The control mechanism of relaxation in molluscan catch-muscle (ABRM). The relaxing effects of 5-hydroxytryptamine (5-HT) have been tested on glycerol-extracted and chemically treated fibres (EDTA and Triton X-100 at two ionic strengths (0.06 and 0.28) and two pH's (6.5 and 7.0). The resistance to stretch of the two muscle preparations has been studied in the low Ca2+ medium i.e. without contractile activity in presence and in absence of 5-HT. The presence of 5-HT reduces significantly the resistance to stretch of chemically treated fibers in conditions of ionic strength 0.28 and 7.0, but has no effect on glycerol extracted fibres. 2. After the maximal tension has been developed in a high Ca2+ solution (10-6 M) the rate of relaxation of chemically treated fibres, induced by a low Ca2+ solution (10-9 M) at ionic strength 0.28 and pH 7.0 is increased by the addition of 5-HT. No effect is observed in glycerol extreacted fibres. 3. Chemically treated fibres in catch-state induced at ionic strength 0.28 and pH 6.5. 4. Cyclic AMP (c-AMP) induces the same relaxing effects at 5-HT on chemically treated fibres in the same conditions of ionic strength, pH and Ca2+ concentration. 5. The results are in disagreement with the hypothesis that the catch-state in ABRM is due to a lowering of the intracellular strength and pH; they suggest that the intracellular physiological conditions are rather near ionic strength 0.28 and pH 7.0 even in catch-state. We suppose that the relaxing effect of 5-HT, is not be due to a decrease of the intracellular free Ca2+ level but rather to an increase of the rate of Ca2+ release from the contractile proteins, and that it is mediated through c-AMP and intracellular relaxing mediator."}
{"id": "PMID:237256", "title": "Purification of S1 muclease from Takadiastase by affinity chromatography on single-stranded DNA-acrylamide columns.", "content": "When S1 nuclease from Takadiastase was partially purified according to previously reported methods, it showed a 10 to 15 fold increase in specificactivity. Although such preparations were highly active on single-stranded DNA, they had traces of activity on native DNA and were contaminated by T1-RNase. The S1 enzyme was further purified by a single step of affinity chromatography on single-stranded DNA-acrylamide column to a final purification of 275-fold. This preparation was free of T1-RNase and had an absolute specificity for single-stranded DNA.", "contents": "Purification of S1 muclease from Takadiastase by affinity chromatography on single-stranded DNA-acrylamide columns. When S1 nuclease from Takadiastase was partially purified according to previously reported methods, it showed a 10 to 15 fold increase in specificactivity. Although such preparations were highly active on single-stranded DNA, they had traces of activity on native DNA and were contaminated by T1-RNase. The S1 enzyme was further purified by a single step of affinity chromatography on single-stranded DNA-acrylamide column to a final purification of 275-fold. This preparation was free of T1-RNase and had an absolute specificity for single-stranded DNA."}
{"id": "PMID:237257", "title": "A rapid assay technique for RNA ribose methylases.", "content": "A rapid technique for quantitative separation of ribose-methylated nucleosides from base-methylated and non-methylated nucleosides by chromatography on DEAE-cellulose paper in the presence of borate is described. The method has been used as an assay for tRNA ribose methylases from yeast, using under methylated Escherichia coli tRNA as substrate. The main product formed with a partly purified yeast enzyme was characterized as 2'-O-methylcytidine.", "contents": "A rapid assay technique for RNA ribose methylases. A rapid technique for quantitative separation of ribose-methylated nucleosides from base-methylated and non-methylated nucleosides by chromatography on DEAE-cellulose paper in the presence of borate is described. The method has been used as an assay for tRNA ribose methylases from yeast, using under methylated Escherichia coli tRNA as substrate. The main product formed with a partly purified yeast enzyme was characterized as 2'-O-methylcytidine."}
{"id": "PMID:237265", "title": "Short-term effects of sodium pentobarbital on blood gases and chemistry in young chickens.", "content": "Sodium pentobarbital, in its commercially prepared propylene glycol-ethanol-saline vehicle, was given intravenously to 8-week-old male and female Athens Randombred chickens, and either the vehicle alone or 0.8% saline was given to similar groups. One minute after injection, blood samples were taken for blood pH, pCO2, HCO3 minus, corticosterone, total protein, or cholesterol levels. The pO2 was significantly lower in the pentobarbital-anaesthetized birds than in those given saline or the vehicle only. Plasma glucose of birds given the vehicle was elevated over that of those given pentobarbital or saline. Triglycerides were significantly higher in plasma of birds given pentobarbital or the vehicle. This increase appeared related to the presence of the glycol moiety in the vehicle.", "contents": "Short-term effects of sodium pentobarbital on blood gases and chemistry in young chickens. Sodium pentobarbital, in its commercially prepared propylene glycol-ethanol-saline vehicle, was given intravenously to 8-week-old male and female Athens Randombred chickens, and either the vehicle alone or 0.8% saline was given to similar groups. One minute after injection, blood samples were taken for blood pH, pCO2, HCO3 minus, corticosterone, total protein, or cholesterol levels. The pO2 was significantly lower in the pentobarbital-anaesthetized birds than in those given saline or the vehicle only. Plasma glucose of birds given the vehicle was elevated over that of those given pentobarbital or saline. Triglycerides were significantly higher in plasma of birds given pentobarbital or the vehicle. This increase appeared related to the presence of the glycol moiety in the vehicle."}
{"id": "PMID:237267", "title": "Utilization of L-cystine by the gamma-glutamyl transpeptidase-gamma-glutamyl cyclotransferase pathway.", "content": "Cystine is a good acceptor of the gamma-glutamyl group of gamma-glutamyl donors in the reaction catalyzed by gamma-glutamyl transpeptidase. The product of the enzymatic reaction and an authentic sample of gamma-glutamylcystine were shown to exhibit identical chromatographic and electrophoretic behaviors; acid hydrolysis gave equimolar amounts of cystine and glutamate. In studies with two gamma-glutamyl donors, apparent Km values in the neighborhood of 0.3 mM were found for L-cystine; these values are not far from the concentrations of L-cystine in mammalian blood plasma. At an amino-acid acceptor concentration of about 0.5 mM, L-cystine is somewhat more active than L-glutamine, and much more active than L-cystein. L-gamma-Glutamyl-L-cystine was found to be a good substrate of gamma-glutamyl cyclotransferase. These observations thus indicate that L-cystine is a very active substrate of the gamma-glutamyl transpeptidase-gamma-glutamyl cyclotransferase pathway. In relation to the hypothesis that the gamma-glutamyl cycle functions in animo-acid transport, it may be significant that glutathione (which is the most abundant intracellular form) is a much better gamma-glutamyl donor than glutathione disulfide, while the predominant extracellular form-cystine-is a much better gamma-glutamyl acceptor substrate than cystein.", "contents": "Utilization of L-cystine by the gamma-glutamyl transpeptidase-gamma-glutamyl cyclotransferase pathway. Cystine is a good acceptor of the gamma-glutamyl group of gamma-glutamyl donors in the reaction catalyzed by gamma-glutamyl transpeptidase. The product of the enzymatic reaction and an authentic sample of gamma-glutamylcystine were shown to exhibit identical chromatographic and electrophoretic behaviors; acid hydrolysis gave equimolar amounts of cystine and glutamate. In studies with two gamma-glutamyl donors, apparent Km values in the neighborhood of 0.3 mM were found for L-cystine; these values are not far from the concentrations of L-cystine in mammalian blood plasma. At an amino-acid acceptor concentration of about 0.5 mM, L-cystine is somewhat more active than L-glutamine, and much more active than L-cystein. L-gamma-Glutamyl-L-cystine was found to be a good substrate of gamma-glutamyl cyclotransferase. These observations thus indicate that L-cystine is a very active substrate of the gamma-glutamyl transpeptidase-gamma-glutamyl cyclotransferase pathway. In relation to the hypothesis that the gamma-glutamyl cycle functions in animo-acid transport, it may be significant that glutathione (which is the most abundant intracellular form) is a much better gamma-glutamyl donor than glutathione disulfide, while the predominant extracellular form-cystine-is a much better gamma-glutamyl acceptor substrate than cystein."}
{"id": "PMID:237268", "title": "Kinetics of steroid induction and deinduction of tyrosine aminotransferase synthesis in cultured hepatoma cells.", "content": "The specific rate of synthesis of tyrosine aminotransferase (EC 2.6.1.5; L-tyrosine:2-oxoglutarate aminotransferase) is used as a measure of the level of functional, cytoplasmic, tyrosine aminotransferase-specific mRNA in cultured rat hepatoma cells. An analysis of the kinetics of change in this rate after the addition or withdrawal of glucocorticosteroids sets an upper limit on the half-life of the enzyme-specific mRNA of 1-1.5 hr, whether or not steroid is present. The inactivation rate of the enzyme mRNA is independent of the growth condition of the cells, occuring equally rapidly in the presence or absence of serum or insulin, both of which induce tyrosine aminotransferase in these cells. The implications of these results for the mechanism of steroid induction are discussed.", "contents": "Kinetics of steroid induction and deinduction of tyrosine aminotransferase synthesis in cultured hepatoma cells. The specific rate of synthesis of tyrosine aminotransferase (EC 2.6.1.5; L-tyrosine:2-oxoglutarate aminotransferase) is used as a measure of the level of functional, cytoplasmic, tyrosine aminotransferase-specific mRNA in cultured rat hepatoma cells. An analysis of the kinetics of change in this rate after the addition or withdrawal of glucocorticosteroids sets an upper limit on the half-life of the enzyme-specific mRNA of 1-1.5 hr, whether or not steroid is present. The inactivation rate of the enzyme mRNA is independent of the growth condition of the cells, occuring equally rapidly in the presence or absence of serum or insulin, both of which induce tyrosine aminotransferase in these cells. The implications of these results for the mechanism of steroid induction are discussed."}
{"id": "PMID:237269", "title": "Brdicka currents observed with bovine serum albumin and completely reduced bovine serum albumin in the presence of urea.", "content": "In ammonia buffers of varying composition and pH, native bovine serum albumin and completely reduced bovine serum albumin, denoted by p(SH)35, yield quite different Brdicka current-voltage (i-E) curves, but they are identical in the presence of 5 mM calcium chloride. This means that in the presence of calcium, bovine serum albumin becomes completely reduced to p(SH)35. In 8 M urea and ammonia buffers the Brdicka i-E patterns of serum albumin and p(SH)35 are identical even in the absence of calcium, the effect of calcium on the first wave being negligible while calcium slightly increases the second wave. The maximum polarographic effect is attained at urea concentrations of about 5-6 M. Quite generally, the appearance of a second Brdicka wave is attributed to complexation of Co(II) with S- and a group of ligands that is different on the second than on the first wave. The effect of calcium on Brdicka currents of bovine serum albumin in the absence of urea is attributed to an orientation of the protein on the surface of the electrode such that all disulfide groups are reduced and with other ligands can complex with Co(ii). Denaturation of bovine serum albumin in buffers with a pH less than 10.5, and which are 8 M in area, is (polarographically) completely reversible if dilution is made within 15 minutes after preparation. Changes in Brdlcka I-E patterns upon longer aging at varying pH are attributed-in part at least-to dimerization of the denatured protein by interaction of pS- in one molecule with -S-S-in another.", "contents": "Brdicka currents observed with bovine serum albumin and completely reduced bovine serum albumin in the presence of urea. In ammonia buffers of varying composition and pH, native bovine serum albumin and completely reduced bovine serum albumin, denoted by p(SH)35, yield quite different Brdicka current-voltage (i-E) curves, but they are identical in the presence of 5 mM calcium chloride. This means that in the presence of calcium, bovine serum albumin becomes completely reduced to p(SH)35. In 8 M urea and ammonia buffers the Brdicka i-E patterns of serum albumin and p(SH)35 are identical even in the absence of calcium, the effect of calcium on the first wave being negligible while calcium slightly increases the second wave. The maximum polarographic effect is attained at urea concentrations of about 5-6 M. Quite generally, the appearance of a second Brdicka wave is attributed to complexation of Co(II) with S- and a group of ligands that is different on the second than on the first wave. The effect of calcium on Brdicka currents of bovine serum albumin in the absence of urea is attributed to an orientation of the protein on the surface of the electrode such that all disulfide groups are reduced and with other ligands can complex with Co(ii). Denaturation of bovine serum albumin in buffers with a pH less than 10.5, and which are 8 M in area, is (polarographically) completely reversible if dilution is made within 15 minutes after preparation. Changes in Brdlcka I-E patterns upon longer aging at varying pH are attributed-in part at least-to dimerization of the denatured protein by interaction of pS- in one molecule with -S-S-in another."}
{"id": "PMID:237270", "title": "Changes in cyclic nucleotide metabolism in aorta and heart of neurogenically hypertensive rats: possible trigger mechanism of hypertension.", "content": "Changes in cyclic nucleotide metabolism similar to those characteristic of the chronic forms of hypertension were observed in an acute neurogenic form of hypertension in rats produced by electrolytic lesions of the nucleus tractus solitarii. These changes that were evident 2 hr after the lesions were made included decreased cyclic AMP levels in the heart, increased cGMP:cAMP ratio, cAMP phosphodiesterase (3':5'-cAMP 5'-nucleotidohydrolase, EC 3.1.4.17) and guanylyl cyclase (GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2) activities in the aorta and decreased snesitivity of adenylyl cyclase (ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1) in both the aorta and heart to stimulation by the beta-adrenergic stimulant isoproterenol. These changes appear to depend on catecholamine release and are not due to mechanical distortion secondary to the increased arterial pressure. These studies provide biochemical support to the concept that the sympathetic nervous system may play a critical role in the initiation of the hypertensive syndrome and that chronic hypertension could result from the fixation of the biochemical effects of increased sympathetic activity.", "contents": "Changes in cyclic nucleotide metabolism in aorta and heart of neurogenically hypertensive rats: possible trigger mechanism of hypertension. Changes in cyclic nucleotide metabolism similar to those characteristic of the chronic forms of hypertension were observed in an acute neurogenic form of hypertension in rats produced by electrolytic lesions of the nucleus tractus solitarii. These changes that were evident 2 hr after the lesions were made included decreased cyclic AMP levels in the heart, increased cGMP:cAMP ratio, cAMP phosphodiesterase (3':5'-cAMP 5'-nucleotidohydrolase, EC 3.1.4.17) and guanylyl cyclase (GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2) activities in the aorta and decreased snesitivity of adenylyl cyclase (ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1) in both the aorta and heart to stimulation by the beta-adrenergic stimulant isoproterenol. These changes appear to depend on catecholamine release and are not due to mechanical distortion secondary to the increased arterial pressure. These studies provide biochemical support to the concept that the sympathetic nervous system may play a critical role in the initiation of the hypertensive syndrome and that chronic hypertension could result from the fixation of the biochemical effects of increased sympathetic activity."}
{"id": "PMID:237271", "title": "Effects of alkylation of phosphodiesters and of bases of infectivity and stability of tobacco mosaic virus RNA.", "content": "Upon ethyl nitrosourea treatment of RNA of tobacco mosaic virus, up to four phosphodiester groups may be alkylated per molecule without chain breakage, as shown be sucrose gradient centrifugation. This indicates that ribophosphotriesters are quite stable. However, when this alkylation reaction is of longer duration and 6 to 10 triesters are formed, then an average of 1 to 2 breaks occurs and little or no intact RNA can be isolated. Methyl nitrosourea is less effective in forming triesters (about 25% of total alkyl groups compared to about 65% for ethyl nitrosourea), and a greater number of alkyl groups can, therefore, be introduced before breaks occur. Diethyl sulfate and dimethyl sulfate, which alkylate almost only the bases of nucleic acids, do not cause significant degradation of RNA of tobacco mosaic virus, even when as many as 70 alkyl groups are bound. All types of alkylation cause similar losses in viral infectivity at low levels of alkylation. Thus, an average of two chemical events leads to one lethal event, regardless of the nature of the alkylating reaction, which, for example, is with dimethyl sulfate about 65% on the N-7 guanine while with ethyl nitrosourea it is about 65% on phosphodiesters. It is thus concluded that all alkyl groups, whether on the base or on the phosphate, have the same potential to cause inactivation and that inactivation of RNA can result from phosphotriester formation per se.", "contents": "Effects of alkylation of phosphodiesters and of bases of infectivity and stability of tobacco mosaic virus RNA. Upon ethyl nitrosourea treatment of RNA of tobacco mosaic virus, up to four phosphodiester groups may be alkylated per molecule without chain breakage, as shown be sucrose gradient centrifugation. This indicates that ribophosphotriesters are quite stable. However, when this alkylation reaction is of longer duration and 6 to 10 triesters are formed, then an average of 1 to 2 breaks occurs and little or no intact RNA can be isolated. Methyl nitrosourea is less effective in forming triesters (about 25% of total alkyl groups compared to about 65% for ethyl nitrosourea), and a greater number of alkyl groups can, therefore, be introduced before breaks occur. Diethyl sulfate and dimethyl sulfate, which alkylate almost only the bases of nucleic acids, do not cause significant degradation of RNA of tobacco mosaic virus, even when as many as 70 alkyl groups are bound. All types of alkylation cause similar losses in viral infectivity at low levels of alkylation. Thus, an average of two chemical events leads to one lethal event, regardless of the nature of the alkylating reaction, which, for example, is with dimethyl sulfate about 65% on the N-7 guanine while with ethyl nitrosourea it is about 65% on phosphodiesters. It is thus concluded that all alkyl groups, whether on the base or on the phosphate, have the same potential to cause inactivation and that inactivation of RNA can result from phosphotriester formation per se."}
{"id": "PMID:237272", "title": "Dissociation of bovine 6S procarboxypeptidase A by reversible condensation with 2,3-dimethyl maleic anhydride: application to the partial characterization of subunit III.", "content": "Bovine 6S procarboxypeptidase A can be dissociated into its three subunits by acylation with dimethyl maleic anhydride. The deacylated subunits are obtained in a largely native form due to instability of the bonds to dimethyl maleate at pH values near neutrality. The seven first residues of subunit III are identical to residues 18-24 of bovine chymotrypsinogen B and very similar with the same residues in bovine chymotrypsinogen A and C (subunit II) and also in proelastase A of the African lungfish. Therefore, this subunit is likely to be a chymotrypsinogen or proelastase-A-like zymogen which has lost the ability to be activated on account of a deletion of the N-terminal residues from half-cystine 1 to valine 17. Like other pancreatic zymogens, subunit III appears to possess a weakly functional active site.", "contents": "Dissociation of bovine 6S procarboxypeptidase A by reversible condensation with 2,3-dimethyl maleic anhydride: application to the partial characterization of subunit III. Bovine 6S procarboxypeptidase A can be dissociated into its three subunits by acylation with dimethyl maleic anhydride. The deacylated subunits are obtained in a largely native form due to instability of the bonds to dimethyl maleate at pH values near neutrality. The seven first residues of subunit III are identical to residues 18-24 of bovine chymotrypsinogen B and very similar with the same residues in bovine chymotrypsinogen A and C (subunit II) and also in proelastase A of the African lungfish. Therefore, this subunit is likely to be a chymotrypsinogen or proelastase-A-like zymogen which has lost the ability to be activated on account of a deletion of the N-terminal residues from half-cystine 1 to valine 17. Like other pancreatic zymogens, subunit III appears to possess a weakly functional active site."}
{"id": "PMID:237273", "title": "Interaction of hemoglobin with three ligans: organic phosphates and the Bohr effect.", "content": "The assumption that the Bohy coefficient (less than log p 50)/(less than pH) is equal to the haldane coefficient (less than h minus plus) of hemoglobin is shown to be incorrect in the presence of allosteric effectors such as 2,3-diphosphoglycerate. The theoretical relation between the two coefficients in the presence of 2.3-diphosphoglycerate as derived. Experimental data on the variation of both coefficients with diphosphoglycerate concentration are presented and shown to be in agreement with prediction.", "contents": "Interaction of hemoglobin with three ligans: organic phosphates and the Bohr effect. The assumption that the Bohy coefficient (less than log p 50)/(less than pH) is equal to the haldane coefficient (less than h minus plus) of hemoglobin is shown to be incorrect in the presence of allosteric effectors such as 2,3-diphosphoglycerate. The theoretical relation between the two coefficients in the presence of 2.3-diphosphoglycerate as derived. Experimental data on the variation of both coefficients with diphosphoglycerate concentration are presented and shown to be in agreement with prediction."}
{"id": "PMID:237305", "title": "Polyarteritis Nodosa \"mimicking\" eosinophilic gastroenteritis.", "content": "This case of a 71-year-old man with persistent eosinophilia (33-54%), intermittent abdominal pain, and transient pulmonary infiltrates illustrates how polyarteritis nodosa may mimic eosinophilic gastroenteritis. The radiographic manifestations and clinical findings of both are similar.", "contents": "Polyarteritis Nodosa \"mimicking\" eosinophilic gastroenteritis. This case of a 71-year-old man with persistent eosinophilia (33-54%), intermittent abdominal pain, and transient pulmonary infiltrates illustrates how polyarteritis nodosa may mimic eosinophilic gastroenteritis. The radiographic manifestations and clinical findings of both are similar."}
{"id": "PMID:237313", "title": "Kinetic study of neutrophil and inflammatory fluid beta glucuronidase.", "content": "Beta glucuronidase obtained from rat inflammatory fluid and granulocytes was studied kinetically. Linear increases in activity occurred with time and enzyme concentration. No evidence of enzyme degradation during incubation was obtained. Supernatant and granulocyte enzyme activity was identical in relation to Km, and pH optima and resistance to high NaCl concentration. Minimal contributions to supernatant activity occur from plasma and red cells.", "contents": "Kinetic study of neutrophil and inflammatory fluid beta glucuronidase. Beta glucuronidase obtained from rat inflammatory fluid and granulocytes was studied kinetically. Linear increases in activity occurred with time and enzyme concentration. No evidence of enzyme degradation during incubation was obtained. Supernatant and granulocyte enzyme activity was identical in relation to Km, and pH optima and resistance to high NaCl concentration. Minimal contributions to supernatant activity occur from plasma and red cells."}
{"id": "PMID:237314", "title": "Effects of experimental bilateral cryptorchidism and castration on the plasma gonadotropins in male rats during sexual maturation.", "content": "The effect of bilateral cryptorchidism and castration on serum LH and FSH was assessed in rats throughout their sexual maturation. After short time (4 days) castration marked elevations of FSH and increases of LH in plasma are recorded in all developmental stages. Bilateral cryptorchidism caused after 4 days in different age groups elevations of LH regardless of the sexual maturation. FSH was elevated in these cryptorchid animals only in more mature animals.", "contents": "Effects of experimental bilateral cryptorchidism and castration on the plasma gonadotropins in male rats during sexual maturation. The effect of bilateral cryptorchidism and castration on serum LH and FSH was assessed in rats throughout their sexual maturation. After short time (4 days) castration marked elevations of FSH and increases of LH in plasma are recorded in all developmental stages. Bilateral cryptorchidism caused after 4 days in different age groups elevations of LH regardless of the sexual maturation. FSH was elevated in these cryptorchid animals only in more mature animals."}
{"id": "PMID:237315", "title": "Degrees of saturation with respect to apatites in fruit juices and acidic drinks.", "content": "Some fruit juices and carbonated acidic drinks, recognized as agents causing dental erosions, were analyzed for calcium, phosphate, fluoride and pH. Ionic activity/concentration products for hydroxyapatite and fluorapatite were calculated. It was found that all liquids analyzed were unsaturated with respect to both apatites, which explains their erosive effect.", "contents": "Degrees of saturation with respect to apatites in fruit juices and acidic drinks. Some fruit juices and carbonated acidic drinks, recognized as agents causing dental erosions, were analyzed for calcium, phosphate, fluoride and pH. Ionic activity/concentration products for hydroxyapatite and fluorapatite were calculated. It was found that all liquids analyzed were unsaturated with respect to both apatites, which explains their erosive effect."}
{"id": "PMID:237316", "title": "Degrees of saturation with respect to apatites in parotid saliva at various ph values.", "content": "The purpose of the present work was to investigate the degrees of saturation with respect to hydroxyapatite and fluorapatite in saliva at various pH's. The data of ionic activities in parotid saliva were collected from the literature and the degrees of saturation with respect to hydroxyapatite and fluorapatite were calculated. It was found that parotid saliva was supersaturated with respect to both apatites above pH 5.5, unsaturated with respect to hydroxyapatite and concurrently supersaturated with respect to fluorapatite in the pH range 5.5-4.5, while it was unsaturated with respect to both apatities below pH 4.5. In the laboratory it has been found that when enamel is exposed to a liquid unsaturated with respect to hydroxyapatite and supersaturated with respect to fluorapatite, a caries-like lesion is developed. A liquid unsaturated with respect to both apatites leads to an erosion-like injury. It is concluded that the two chemical conditions leading to the two types of enamel lesions may both occur in the oral cavity.", "contents": "Degrees of saturation with respect to apatites in parotid saliva at various ph values. The purpose of the present work was to investigate the degrees of saturation with respect to hydroxyapatite and fluorapatite in saliva at various pH's. The data of ionic activities in parotid saliva were collected from the literature and the degrees of saturation with respect to hydroxyapatite and fluorapatite were calculated. It was found that parotid saliva was supersaturated with respect to both apatites above pH 5.5, unsaturated with respect to hydroxyapatite and concurrently supersaturated with respect to fluorapatite in the pH range 5.5-4.5, while it was unsaturated with respect to both apatities below pH 4.5. In the laboratory it has been found that when enamel is exposed to a liquid unsaturated with respect to hydroxyapatite and supersaturated with respect to fluorapatite, a caries-like lesion is developed. A liquid unsaturated with respect to both apatites leads to an erosion-like injury. It is concluded that the two chemical conditions leading to the two types of enamel lesions may both occur in the oral cavity."}
{"id": "PMID:237317", "title": "In vivo studies on the neutralizing effect of antacids using the Heidelberg capsule.", "content": "The effects on gastric pH of various forms of administration of antacids have been studied in healthy volunteers. Gastric pH was recorded using a radiotelemetric technique (Heidelberg Capsules). In one series of experiments the Heidelberg Capsules were compared with a conventional aspiration method of measuring gastric pHqt lower pH-levels (pH smaller than 2) the Heidelberg Capsules recorded lower values than what was found with the aspiration technique. However, when the pH-response to an antacid dose was studied the two techniques gave concordant results. In another series of experiments, four antacids with the same acid-neutralizing capacity in vitro were compared in fasting subjects, using a crossover design. A liquid preparation and a chewable tablet gave almost equal results with a short latency time and a duration of action of more than one hour (mean 69 minutes and 82 minutes, respectively, with pH above the basal level). Two other tablet antacids designed to be swallowed whole gave less prompt effects and a shorter duration of action (mean 45 minutes for both, with pH above the basal level).", "contents": "In vivo studies on the neutralizing effect of antacids using the Heidelberg capsule. The effects on gastric pH of various forms of administration of antacids have been studied in healthy volunteers. Gastric pH was recorded using a radiotelemetric technique (Heidelberg Capsules). In one series of experiments the Heidelberg Capsules were compared with a conventional aspiration method of measuring gastric pHqt lower pH-levels (pH smaller than 2) the Heidelberg Capsules recorded lower values than what was found with the aspiration technique. However, when the pH-response to an antacid dose was studied the two techniques gave concordant results. In another series of experiments, four antacids with the same acid-neutralizing capacity in vitro were compared in fasting subjects, using a crossover design. A liquid preparation and a chewable tablet gave almost equal results with a short latency time and a duration of action of more than one hour (mean 69 minutes and 82 minutes, respectively, with pH above the basal level). Two other tablet antacids designed to be swallowed whole gave less prompt effects and a shorter duration of action (mean 45 minutes for both, with pH above the basal level)."}
{"id": "PMID:237318", "title": "Genetic control of the in vitro responses of rat blood lymphocytes. I. Comparison of in vitro and in vivo responses.", "content": "Nielsen, H. E. & Koch, C. Genetic Control of the In Vitro Responses of Rat Blood Lymphocytes. I. Comparison of In Vitro and In Vivo Responses, Scand. J. Immunol. 4, 31-36, 1975. In vitro DNA synthetic responses of blood lymphocytes from the inbred rat strains BN, Lewis, and AS were compared with each other after stimulation with allogeneic lymphocytes, human lymphocytes, phytohemagglutinin, and anti-Ig antibodies. BN lymphocytes responded less well than AS and Lewis lymphocytes regardless of the stimulus used. The responses of the congenic strains Lewis and Lewis. BN were identical, suggesting that H-1 (Ag-B)-linked loci do not determine in vitro responsiveness in these strains. In vivo, AS and BN rats were equally able to reject third-party skin grafts and to induce graft-versus-host reactions in F1 hybrids. We conclude that the interstrain differences found in vitro reflect genetically determined differences in in vitro kinetics, possibly related to the fraction of short-lived lymphocytes present rather than to demonstrable differences in the frequency of reactive lymphocytes.", "contents": "Genetic control of the in vitro responses of rat blood lymphocytes. I. Comparison of in vitro and in vivo responses. Nielsen, H. E. & Koch, C. Genetic Control of the In Vitro Responses of Rat Blood Lymphocytes. I. Comparison of In Vitro and In Vivo Responses, Scand. J. Immunol. 4, 31-36, 1975. In vitro DNA synthetic responses of blood lymphocytes from the inbred rat strains BN, Lewis, and AS were compared with each other after stimulation with allogeneic lymphocytes, human lymphocytes, phytohemagglutinin, and anti-Ig antibodies. BN lymphocytes responded less well than AS and Lewis lymphocytes regardless of the stimulus used. The responses of the congenic strains Lewis and Lewis. BN were identical, suggesting that H-1 (Ag-B)-linked loci do not determine in vitro responsiveness in these strains. In vivo, AS and BN rats were equally able to reject third-party skin grafts and to induce graft-versus-host reactions in F1 hybrids. We conclude that the interstrain differences found in vitro reflect genetically determined differences in in vitro kinetics, possibly related to the fraction of short-lived lymphocytes present rather than to demonstrable differences in the frequency of reactive lymphocytes."}
{"id": "PMID:237319", "title": "Local graft-versus-host-reaction in mice specifically inhibited by anti-receptor antibodies.", "content": "The local graft-versus-host (GVH) reaction provoked by parental spleen cells in F1 mice was shown to be T-cell-dependent. GVH reactions were suppressed in F1 hybrid mice immunized with parental T lymphocytes of the same genotype, but not in F1 mice immunized with parental B cells. In some cases this immunity could be passively transferred by serum into normal F1 mice. The specific activity of such sera could be removed by absorption with either parental T or B cells. Some of the F1 antisera were specificlly cytotoxic for parental GVH-reactive lymphocytes.", "contents": "Local graft-versus-host-reaction in mice specifically inhibited by anti-receptor antibodies. The local graft-versus-host (GVH) reaction provoked by parental spleen cells in F1 mice was shown to be T-cell-dependent. GVH reactions were suppressed in F1 hybrid mice immunized with parental T lymphocytes of the same genotype, but not in F1 mice immunized with parental B cells. In some cases this immunity could be passively transferred by serum into normal F1 mice. The specific activity of such sera could be removed by absorption with either parental T or B cells. Some of the F1 antisera were specificlly cytotoxic for parental GVH-reactive lymphocytes."}
{"id": "PMID:237320", "title": "[Cerebral sclerosis. Diagnostic criteria and differential diagnostic consideration in practice].", "content": "In\"cerebral arteriosclerosis\" the diffuse sclerotic involvement of the cerebral vessels may produce acute softening of cerebral tissue. However this paper concentrates mainly on the clinical symptomatology which, in the absence of major vascular accidents, is characterized from the psychopathologic viewpoint by acute confusional states, aggressive behaviour, fluctuating loss of memory, disturbances of concentration and finally dementia. The chief neurologic symptoms are motor disturbance with short-stepping gait, stooped position of the body, pseudobulbar symptoms with dysarthric speech and disturbances of swallowing, and increased perioral reflexes. A complete case history and a thorough neurologic and psychopathologic examination are the most important factors in diagnosis, while ancillary methods are of value only for differential diagnosis. Prophylaxis and therapy (cardiotherapy, treatment of diabetes and hypertension, lowering of serum cholesterol and sedation) are discussed. In the differential diagnosis of dementia in the elderly patient consideration should be given to chronic vascular diseases, degenerative cerebral atrophies, brain tumors, low pressure hydrocephalus, progressive paralysis and some other rare brain conditions.", "contents": "[Cerebral sclerosis. Diagnostic criteria and differential diagnostic consideration in practice]. In\"cerebral arteriosclerosis\" the diffuse sclerotic involvement of the cerebral vessels may produce acute softening of cerebral tissue. However this paper concentrates mainly on the clinical symptomatology which, in the absence of major vascular accidents, is characterized from the psychopathologic viewpoint by acute confusional states, aggressive behaviour, fluctuating loss of memory, disturbances of concentration and finally dementia. The chief neurologic symptoms are motor disturbance with short-stepping gait, stooped position of the body, pseudobulbar symptoms with dysarthric speech and disturbances of swallowing, and increased perioral reflexes. A complete case history and a thorough neurologic and psychopathologic examination are the most important factors in diagnosis, while ancillary methods are of value only for differential diagnosis. Prophylaxis and therapy (cardiotherapy, treatment of diabetes and hypertension, lowering of serum cholesterol and sedation) are discussed. In the differential diagnosis of dementia in the elderly patient consideration should be given to chronic vascular diseases, degenerative cerebral atrophies, brain tumors, low pressure hydrocephalus, progressive paralysis and some other rare brain conditions."}
{"id": "PMID:237321", "title": "Practical problems in the treatment of pain.", "content": "According to modern pain concepts, \"pain\" is the result of multifactorial influences. Planning of therapy therefore requires the diagnostic evaluation of a number of factors including delineation of an organic lesion, evaluation of the influence of pain on the individual's psychological development, situational anxiety, psychological coping style etc. The understanding and management of psychological factors is crucial in every pain syndrome as the idea the pain is either psychogenic or organic is outdated. For the treatment of mild pain salicylic acid is still unsurpassed. The rationale of its combination with a tranquillizer, and with codeine or benzomorphane for moderately severe pain, can be understood on the basis of modern pain concepts. Before strong narcotics are used a trial with combination of a phenothiazine with a tricyclic antidepressant drug is warranted. Methadone seems to have advantages over morphine for very distressing pain treated with narcotics. Biofeedback for pain due to muscle spasms, electrical stimulation of the dorsal column for intense chronic pain due to a well-delineated organic lesion, and operant conditioning applied by a well-trained team of physicians and staff are promising new treatments for pain. The place of acupuncture in future pain therapy cannot yet be judged. It must first be freed of cult-type opinions and evaluated further by studies meeting modern western standards of pain research.", "contents": "Practical problems in the treatment of pain. According to modern pain concepts, \"pain\" is the result of multifactorial influences. Planning of therapy therefore requires the diagnostic evaluation of a number of factors including delineation of an organic lesion, evaluation of the influence of pain on the individual's psychological development, situational anxiety, psychological coping style etc. The understanding and management of psychological factors is crucial in every pain syndrome as the idea the pain is either psychogenic or organic is outdated. For the treatment of mild pain salicylic acid is still unsurpassed. The rationale of its combination with a tranquillizer, and with codeine or benzomorphane for moderately severe pain, can be understood on the basis of modern pain concepts. Before strong narcotics are used a trial with combination of a phenothiazine with a tricyclic antidepressant drug is warranted. Methadone seems to have advantages over morphine for very distressing pain treated with narcotics. Biofeedback for pain due to muscle spasms, electrical stimulation of the dorsal column for intense chronic pain due to a well-delineated organic lesion, and operant conditioning applied by a well-trained team of physicians and staff are promising new treatments for pain. The place of acupuncture in future pain therapy cannot yet be judged. It must first be freed of cult-type opinions and evaluated further by studies meeting modern western standards of pain research."}
{"id": "PMID:237322", "title": "Amino acid composition of proteins: Selection against the genetic code.", "content": "Distribution of amino acids in 68 representative proteins is compared with their distribution among 61 codons of the genetic code. Average amounts of lysine, aspartic acid, glutamic acid, and alanine are above the levels anticipated from the genetic code, and arginine, serine, leucine, cysteine, proline, and histidine are below such levels. Arginine plus lysine account for 11.0 percent of codons and aspartic acid plus glutamic acid account for 11.3 percent; thus the average charge is roughly neutral.", "contents": "Amino acid composition of proteins: Selection against the genetic code. Distribution of amino acids in 68 representative proteins is compared with their distribution among 61 codons of the genetic code. Average amounts of lysine, aspartic acid, glutamic acid, and alanine are above the levels anticipated from the genetic code, and arginine, serine, leucine, cysteine, proline, and histidine are below such levels. Arginine plus lysine account for 11.0 percent of codons and aspartic acid plus glutamic acid account for 11.3 percent; thus the average charge is roughly neutral."}
{"id": "PMID:237324", "title": "The drug management of acute behavioural disturbances.", "content": "Some aspects of drug management of acute behavioural disorder are discussed. Drug management aims at the amelioration of the patient's ineraction with his environment; it is used as a diagnostic procedure, and to facilitate further definitive diagnosis and investigation, as a form of psychotherapeutic contact, to facilitate further psychotherapy, and to initiate a treatment programme aimed at returning the patient to being a useful and health member of society. Some methods of rapid tranquillisation are described and the drug management of the following specific behavioural disturbances are discussed: schizophrenic distrubance, acute mania, depressive behavioural disturbance, acute anxiety states, acting-out psychopathic behaviour, toxic states, epileptic furore and dyscontrol syndrome, behavioural disturbances of the elderly, and behavioural disturbances in organic conditions.", "contents": "The drug management of acute behavioural disturbances. Some aspects of drug management of acute behavioural disorder are discussed. Drug management aims at the amelioration of the patient's ineraction with his environment; it is used as a diagnostic procedure, and to facilitate further definitive diagnosis and investigation, as a form of psychotherapeutic contact, to facilitate further psychotherapy, and to initiate a treatment programme aimed at returning the patient to being a useful and health member of society. Some methods of rapid tranquillisation are described and the drug management of the following specific behavioural disturbances are discussed: schizophrenic distrubance, acute mania, depressive behavioural disturbance, acute anxiety states, acting-out psychopathic behaviour, toxic states, epileptic furore and dyscontrol syndrome, behavioural disturbances of the elderly, and behavioural disturbances in organic conditions."}
{"id": "PMID:237325", "title": "Total body potassium, acid-base status and serum electrolytes in acute diarrhoeal disease.", "content": "Total body potassium (TBK), acid-base status and serum electrolyte concentrations were measured in 49 children suffering from acute diarrhoeal disease, on admission and after rehydration. The TBK was usually low and the lowest values were found in those with the lowest pH. There was no relationship between TBK and serum sodium or potassium concentrations. Hyponatraemia was common as would be expected in a series containing many underweight children.", "contents": "Total body potassium, acid-base status and serum electrolytes in acute diarrhoeal disease. Total body potassium (TBK), acid-base status and serum electrolyte concentrations were measured in 49 children suffering from acute diarrhoeal disease, on admission and after rehydration. The TBK was usually low and the lowest values were found in those with the lowest pH. There was no relationship between TBK and serum sodium or potassium concentrations. Hyponatraemia was common as would be expected in a series containing many underweight children."}
{"id": "PMID:237326", "title": "Treatment of hypertension with the aid of beta-adrenergic blocking drugs.", "content": "Beta-adrenergic blocking drugs have become a recognized addition to the hypotensive agents. This article reviews the current beta-blocking agents, with regard to their usage, side-effects and role in the treatment of hypertension.", "contents": "Treatment of hypertension with the aid of beta-adrenergic blocking drugs. Beta-adrenergic blocking drugs have become a recognized addition to the hypotensive agents. This article reviews the current beta-blocking agents, with regard to their usage, side-effects and role in the treatment of hypertension."}
{"id": "PMID:237328", "title": "Anxiety: its nature and treatment.", "content": "Anxiety is an unpleasant, diffuse emotion, directed towards the future and associated with feelings of threat to the individual. Clinical anxiety occurs when a patient suffers from anxiety which is more frequent, more severe or more persistent than he is used to and can tolerate. Almost a third of the adult population will admit to some symptoms of anxiety. Drug therapy, in particular the benzodiazepines, is the mainstay of treatment, but care must be taken to avoid overprescription.", "contents": "Anxiety: its nature and treatment. Anxiety is an unpleasant, diffuse emotion, directed towards the future and associated with feelings of threat to the individual. Clinical anxiety occurs when a patient suffers from anxiety which is more frequent, more severe or more persistent than he is used to and can tolerate. Almost a third of the adult population will admit to some symptoms of anxiety. Drug therapy, in particular the benzodiazepines, is the mainstay of treatment, but care must be taken to avoid overprescription."}
{"id": "PMID:237331", "title": "Nitrogen sparing by carbohydrate in man: Intermittent or continuous enteral compared with continuous parenteral glucose.", "content": "To test whether oral carbohydrate would provide greater conservation of body protein than would intravenous carbohydrate, healthy normal human subjects were infused with high doses of glucose either continuously intravenously or by nasogastric tube in both continuous and intermittent regimes. Metabolic responses to high calorie, nitrogen-free infusions in normal man were documented in the blood hormone and substrate changes, and protein sparing was assessed by urinary nitrogen excretion. Continuous glucose produced a lower urinary \"nitrogen floor\" than did the intermittent regime, and intravenous glucose was more effective than was oral glucose. The insulin responses to continuous nasogastric and continuous intravenous glucose were similar, and nitrogen excretion did not differ between those two groups. The increased insulin levels seen with intermittent glucose were not accompanied by greater protein sparing.", "contents": "Nitrogen sparing by carbohydrate in man: Intermittent or continuous enteral compared with continuous parenteral glucose. To test whether oral carbohydrate would provide greater conservation of body protein than would intravenous carbohydrate, healthy normal human subjects were infused with high doses of glucose either continuously intravenously or by nasogastric tube in both continuous and intermittent regimes. Metabolic responses to high calorie, nitrogen-free infusions in normal man were documented in the blood hormone and substrate changes, and protein sparing was assessed by urinary nitrogen excretion. Continuous glucose produced a lower urinary \"nitrogen floor\" than did the intermittent regime, and intravenous glucose was more effective than was oral glucose. The insulin responses to continuous nasogastric and continuous intravenous glucose were similar, and nitrogen excretion did not differ between those two groups. The increased insulin levels seen with intermittent glucose were not accompanied by greater protein sparing."}
{"id": "PMID:237336", "title": "Scanning electron microscopic and electrophoretic observations on barium sulphate used to absorb clotting factors.", "content": "Electron microscopy and particle electrophoresis were found to be complementary techniques with which to complete the physical data from an earlier study on barium sulphates used to absorb clotting factors from serum. The differences revealed by scanning electron microscopy (S. E. M) in the physical shape of low and high density grades of barium sulphate particles appear to be of greater significance than charge as expressed by electrophoretic mobility, in determining whether or not precursor or performed factor Xa is eluted. This conclusion was based on the finding that at pH values close to 7, where the adsorption from serum occurs, all samples with the exception of natural barytes were uncharged. However as the high-density, or soil-grade, was found by S. E. M. to consist of large solid crystals it was suggested that this shape might induce activiation of factor X as a result of partial denaturation and consequent unfolding of the adsorbed protein. In contrast, uptake of protein into the centre of the porous aggregates revealed by S. E. M. pictures of low-density or X-ray grade barium sulphate may afford protection against denaturation and exposure of the enzyme site. The porous nature of particles of low-density barium sulphate compared with the solid crystalline forms of other grades accounts not only for its lower bulk density but also for its greater surface/gram ratio which is reflected by an ability to adsorb more protein from serum. Neither technique produced evidence from any of the samples to indicate the presence of stabilising agents sometimes used to coat particles in barium meals.", "contents": "Scanning electron microscopic and electrophoretic observations on barium sulphate used to absorb clotting factors. Electron microscopy and particle electrophoresis were found to be complementary techniques with which to complete the physical data from an earlier study on barium sulphates used to absorb clotting factors from serum. The differences revealed by scanning electron microscopy (S. E. M) in the physical shape of low and high density grades of barium sulphate particles appear to be of greater significance than charge as expressed by electrophoretic mobility, in determining whether or not precursor or performed factor Xa is eluted. This conclusion was based on the finding that at pH values close to 7, where the adsorption from serum occurs, all samples with the exception of natural barytes were uncharged. However as the high-density, or soil-grade, was found by S. E. M. to consist of large solid crystals it was suggested that this shape might induce activiation of factor X as a result of partial denaturation and consequent unfolding of the adsorbed protein. In contrast, uptake of protein into the centre of the porous aggregates revealed by S. E. M. pictures of low-density or X-ray grade barium sulphate may afford protection against denaturation and exposure of the enzyme site. The porous nature of particles of low-density barium sulphate compared with the solid crystalline forms of other grades accounts not only for its lower bulk density but also for its greater surface/gram ratio which is reflected by an ability to adsorb more protein from serum. Neither technique produced evidence from any of the samples to indicate the presence of stabilising agents sometimes used to coat particles in barium meals."}
{"id": "PMID:237337", "title": "The significance of malate dehydrogenase isoenzymes in human blood platelets.", "content": "Two MDH isoenzymes were detected in the homogenate of normal human blood platelets. According to their properties the cationic isoenzyme is compartmentalized in the mitochondria, the anionic one belongs to the cytoplasma. In spite of the few mitochondria in human blood platelets the proportion of the cationic enzyme is relatively high. Both of these enzymes could belong to a transfer system for malate transport across the mitochondrial membrane. As human blood platelets do not contain creatine phosphate a system like that could be of significance for platelet function.", "contents": "The significance of malate dehydrogenase isoenzymes in human blood platelets. Two MDH isoenzymes were detected in the homogenate of normal human blood platelets. According to their properties the cationic isoenzyme is compartmentalized in the mitochondria, the anionic one belongs to the cytoplasma. In spite of the few mitochondria in human blood platelets the proportion of the cationic enzyme is relatively high. Both of these enzymes could belong to a transfer system for malate transport across the mitochondrial membrane. As human blood platelets do not contain creatine phosphate a system like that could be of significance for platelet function."}
{"id": "PMID:237344", "title": "Radiocurability of a transplantable murine sarcoma as influenced by immune competence of the host and adjuvant active specific immunotherapy.", "content": "The immunization induced in CBA mice by allogenic transplantation of sarcoma J was evaluated through the rejection rate of a subsequent isologous tumour graft. Female animals appear to be significantly much more competent at various stages of sarcoma growth as after their definite cure by radiation or surgery. A difference of response according to the sex is also present with regard to the auto-immune reaction evoked by tumour irradiation. A marked discrepancy in radiotherapy efficiency is linked to the disparity of immune behaviour, emphasizing the fact that an immunologically competent host constitutes an important factor of tumour radiocurability. In male recipients, an adjuvant active specific immunotherapy potentiates tumour response to a single dose of radiations. On the contrary, the adjunct treatment may display a detrimental effect in animals which already possess a high degree of anti-tumour immunization.", "contents": "Radiocurability of a transplantable murine sarcoma as influenced by immune competence of the host and adjuvant active specific immunotherapy. The immunization induced in CBA mice by allogenic transplantation of sarcoma J was evaluated through the rejection rate of a subsequent isologous tumour graft. Female animals appear to be significantly much more competent at various stages of sarcoma growth as after their definite cure by radiation or surgery. A difference of response according to the sex is also present with regard to the auto-immune reaction evoked by tumour irradiation. A marked discrepancy in radiotherapy efficiency is linked to the disparity of immune behaviour, emphasizing the fact that an immunologically competent host constitutes an important factor of tumour radiocurability. In male recipients, an adjuvant active specific immunotherapy potentiates tumour response to a single dose of radiations. On the contrary, the adjunct treatment may display a detrimental effect in animals which already possess a high degree of anti-tumour immunization."}
{"id": "PMID:237349", "title": "Effect of antithymocyte globulin pretreatment on immunological reconstitution of lethally irradiated animals.", "content": "Clinical and experimental studies have shown that antithymocyte globulin pretreatment will reduce the severity of the graft-versus-host reaction after allogeneic bone marrow transplantation. To determine whether this was attributable to a persisting cytotoxic factor in the recipients' sera or a result of the \"masking\" of foreign antigens by the antihymocyte globulin, an experimental schema utilizing a syngeneic transfer of immunocompetent cells was devised. Lethally irradiated mice that had been pretreated with rabbit antimouse thymocyte globulin (RAMTG) were injected with syngeneic spleen or bone marrow cells and their immunological competence was measured by the response to a test antigen, sheep red blood cells. It was found that such pretreatment had an adverse effect on the immunological potential of the infused cells. Thus, the plaque-forming cell response to sheep red blood cell antigen in RAMTG-pretreated recipients injected with spleen cells was reduced when compared to the saline or normal rabbit globulin-treated controls. The immunological recovery of lethally irradiated animals protected with syngeneic bone marrow was also delayed, but not permanently impaired, when the recipients had been pretreated with RAMTG. These effects were evident although the spleen or bone marrow cells had been injected into the RAMTG-pretreated recipients at a time when their sera were devoid of any cytotoxic antibodies. It is speculated that two mechanisms may contribute to this alteration in immune function of the infused cells: (1) that RAMTG exists in the serum in amounts sufficient to attach to receptor sites on lymphocytes or their precursors but insufficient to kill the cells, interfering with the antigen recognition mechanism or migration and homing patterns, or (2) that the RAMTG treatment creates a temporary defect in the microenvironment of the spleen and other hemopoietic tissues, thereby affecting the transplantation and proliferation kinetics of the infused cells.", "contents": "Effect of antithymocyte globulin pretreatment on immunological reconstitution of lethally irradiated animals. Clinical and experimental studies have shown that antithymocyte globulin pretreatment will reduce the severity of the graft-versus-host reaction after allogeneic bone marrow transplantation. To determine whether this was attributable to a persisting cytotoxic factor in the recipients' sera or a result of the \"masking\" of foreign antigens by the antihymocyte globulin, an experimental schema utilizing a syngeneic transfer of immunocompetent cells was devised. Lethally irradiated mice that had been pretreated with rabbit antimouse thymocyte globulin (RAMTG) were injected with syngeneic spleen or bone marrow cells and their immunological competence was measured by the response to a test antigen, sheep red blood cells. It was found that such pretreatment had an adverse effect on the immunological potential of the infused cells. Thus, the plaque-forming cell response to sheep red blood cell antigen in RAMTG-pretreated recipients injected with spleen cells was reduced when compared to the saline or normal rabbit globulin-treated controls. The immunological recovery of lethally irradiated animals protected with syngeneic bone marrow was also delayed, but not permanently impaired, when the recipients had been pretreated with RAMTG. These effects were evident although the spleen or bone marrow cells had been injected into the RAMTG-pretreated recipients at a time when their sera were devoid of any cytotoxic antibodies. It is speculated that two mechanisms may contribute to this alteration in immune function of the infused cells: (1) that RAMTG exists in the serum in amounts sufficient to attach to receptor sites on lymphocytes or their precursors but insufficient to kill the cells, interfering with the antigen recognition mechanism or migration and homing patterns, or (2) that the RAMTG treatment creates a temporary defect in the microenvironment of the spleen and other hemopoietic tissues, thereby affecting the transplantation and proliferation kinetics of the infused cells."}
{"id": "PMID:237350", "title": "Transplantation of autoimmune potential. II. Glomerulonephritis in lethally irradiated DBA/2 recipients of NZB bone marrow cells.", "content": "Lethally irradiated (850 rads) DBA/2 mice which had been transplanted 10 months previously with 2 times 10-6 bone marrow cells from 3-week-old donors of the H-2-histocompatible NZB, BALB/c and DBA/2 strains were examined for manifestations of autoimmune disease. Also studied were lethally irradiated (950 rads) NZB mice grafted with NZB marrow. Strongly positive antinuclear antibody responses were present in all NZB and DBA/2 recipients of NZB marrow, but absent in DBA/2 mice grafted with BALB/c and DBA/2 marrow cells. The antinuclear antibody-positive animals had glomerulonephritis with the deposition of globulin in or along the basement membranes. These observations support the view that the potential for autoantibody formation and subsequent autoimmune disease development is inherent to the NZB hemopoietic stem cell and their progeny.", "contents": "Transplantation of autoimmune potential. II. Glomerulonephritis in lethally irradiated DBA/2 recipients of NZB bone marrow cells. Lethally irradiated (850 rads) DBA/2 mice which had been transplanted 10 months previously with 2 times 10-6 bone marrow cells from 3-week-old donors of the H-2-histocompatible NZB, BALB/c and DBA/2 strains were examined for manifestations of autoimmune disease. Also studied were lethally irradiated (950 rads) NZB mice grafted with NZB marrow. Strongly positive antinuclear antibody responses were present in all NZB and DBA/2 recipients of NZB marrow, but absent in DBA/2 mice grafted with BALB/c and DBA/2 marrow cells. The antinuclear antibody-positive animals had glomerulonephritis with the deposition of globulin in or along the basement membranes. These observations support the view that the potential for autoantibody formation and subsequent autoimmune disease development is inherent to the NZB hemopoietic stem cell and their progeny."}
{"id": "PMID:237351", "title": "Stimulation of rat graft-versus-host reactions by polyinosinic-polycytidylic acid.", "content": "The effect of polyinosinic-polycytidylic acid (poly I:C) treatment on the rat graft-versus-host reaction (GVHR) initiated in parental to F1 hybrid strain combinations differing at either major or minor histocompatibility determinants were studied in three different protocols. 1 A GVHR initiated in juvenile (LBN)F1 recipients and treated concurrently with poly I:C alone produced neither splenomegaly nor dermatitis in these juvenile rats. (2) Pretreatment of L donors with a single injection of poly I:C 3 days before initiation of the GVHR enhanced resultant splenomegaly in the newborn (LBN)F1 recipients. A high poly I:C dose was inhibitory. (3) Newborn recipients which received lymphocytes from L donors and which were concurrently treated with poly I:C developed dermatitis at an accelerated rate. However, poly I:C alone given to newborns mimicked the GVHR by induction of a syndrome characterized by splenomegaly, dermatitis, thymic involution, and body growth retardation. The parental L and (LF)F1 hybrid strain combination differing only at a minor histocompatibility determinant or in an isogenic hybrid combination (LBN)F1 leads to (LBN)F(1) developed no GVHR when recipients were treated with poly I:C. We conclude that poly I:C can stimulate a rat GVHR initiated with unsensitized donor cells differing at a major histocompatibility locus.", "contents": "Stimulation of rat graft-versus-host reactions by polyinosinic-polycytidylic acid. The effect of polyinosinic-polycytidylic acid (poly I:C) treatment on the rat graft-versus-host reaction (GVHR) initiated in parental to F1 hybrid strain combinations differing at either major or minor histocompatibility determinants were studied in three different protocols. 1 A GVHR initiated in juvenile (LBN)F1 recipients and treated concurrently with poly I:C alone produced neither splenomegaly nor dermatitis in these juvenile rats. (2) Pretreatment of L donors with a single injection of poly I:C 3 days before initiation of the GVHR enhanced resultant splenomegaly in the newborn (LBN)F1 recipients. A high poly I:C dose was inhibitory. (3) Newborn recipients which received lymphocytes from L donors and which were concurrently treated with poly I:C developed dermatitis at an accelerated rate. However, poly I:C alone given to newborns mimicked the GVHR by induction of a syndrome characterized by splenomegaly, dermatitis, thymic involution, and body growth retardation. The parental L and (LF)F1 hybrid strain combination differing only at a minor histocompatibility determinant or in an isogenic hybrid combination (LBN)F1 leads to (LBN)F(1) developed no GVHR when recipients were treated with poly I:C. We conclude that poly I:C can stimulate a rat GVHR initiated with unsensitized donor cells differing at a major histocompatibility locus."}
{"id": "PMID:237352", "title": "Retransplantation of human bone marrow. Two immunosuppressive drug regimens.", "content": "A 15-year-old boy with aplastic anemia was successfully retransplanted with matched sibling bone marrow after failure of a first transplant from the same donor. Cyclophosphamide was used as immunosuppression for the first transplant, and cyclophosphamide plus procarbazine plus antithymocyte globulin were used for the second transplant. Laboratory studies of peripheral blood and bone marrow karyotypes and T and B lymphocytes supported the conclusion that immunosuppression was inadequate for the first transplant, but adequate for the second transplant.", "contents": "Retransplantation of human bone marrow. Two immunosuppressive drug regimens. A 15-year-old boy with aplastic anemia was successfully retransplanted with matched sibling bone marrow after failure of a first transplant from the same donor. Cyclophosphamide was used as immunosuppression for the first transplant, and cyclophosphamide plus procarbazine plus antithymocyte globulin were used for the second transplant. Laboratory studies of peripheral blood and bone marrow karyotypes and T and B lymphocytes supported the conclusion that immunosuppression was inadequate for the first transplant, but adequate for the second transplant."}
{"id": "PMID:237353", "title": "Specific inhibition of the graft-versus-host reaction in fetal or neonatal liver chimeras.", "content": "The fetal liver chimera system was used as a model to study the nature of transplantation tolerance in radiation chimeras. A permanent state of tolerance was induced in (C3H/eb times C57BL/6)F1 irradiated mice after reconstitution with parental C57BL/6 fetal or neonatal liver cells. It was found that although enough host hemopoietic cells were present in such chimeras to provide antigenic stimulation, subsequent inoculation of these chimeras with C57BL/6 immunocompetent cells syngeneic to liver donor cells specifically abolished their response against the host. In addition, cells obtained from liver chimeras after their challenge with C57BL cells were unable to produce a graft-versus-host response upon transfer to (C3H/eb times C57BL/6)F1 newborn mice. Transfer of serum of these mice could not prevent immune reactivity of syngeneic C57BL/6 cells neither in the graft-versus-host nor in the mixed lymphocyte culture assays. These observations are compatible with the hypothesis that suppressor cells may differentiate within the fetal liver, which specifically inhibits the immune reactivity of syngeneic cells, and thus leads to the establishment of tolerance.", "contents": "Specific inhibition of the graft-versus-host reaction in fetal or neonatal liver chimeras. The fetal liver chimera system was used as a model to study the nature of transplantation tolerance in radiation chimeras. A permanent state of tolerance was induced in (C3H/eb times C57BL/6)F1 irradiated mice after reconstitution with parental C57BL/6 fetal or neonatal liver cells. It was found that although enough host hemopoietic cells were present in such chimeras to provide antigenic stimulation, subsequent inoculation of these chimeras with C57BL/6 immunocompetent cells syngeneic to liver donor cells specifically abolished their response against the host. In addition, cells obtained from liver chimeras after their challenge with C57BL cells were unable to produce a graft-versus-host response upon transfer to (C3H/eb times C57BL/6)F1 newborn mice. Transfer of serum of these mice could not prevent immune reactivity of syngeneic C57BL/6 cells neither in the graft-versus-host nor in the mixed lymphocyte culture assays. These observations are compatible with the hypothesis that suppressor cells may differentiate within the fetal liver, which specifically inhibits the immune reactivity of syngeneic cells, and thus leads to the establishment of tolerance."}
{"id": "PMID:237354", "title": "Human immunity to rat antigens.", "content": "A test has been devised with the object of assaying immune responsiveness in normal and immunodepressed persons. It has been based on the graft-versus-host model of Ford et al. (Transplantation 10: 258, 1970) and employs rat antigens as the immunological stimuli. Peripheral blood lymphocytes were injected into the hind feet of young Wistar rats, and 7 days later the popliteal lymph nodes were removed and weighed. It was found that the unwanted host-versus-graft activity could be suppressed in the rats by total body irradiation. Inactivated lymphocytes were injected into the right hind foot as a control and the result was expressed as a ratio: weight of left node to weight of right node. Lymphocytes from 45 healthy individuals were examined in this way. The response was readily suppressed by administering daily injections of steroid or antilymphocyte globulin to the rats, but was not influenced by the presence or absence of antirat antibodies in these individuals.", "contents": "Human immunity to rat antigens. A test has been devised with the object of assaying immune responsiveness in normal and immunodepressed persons. It has been based on the graft-versus-host model of Ford et al. (Transplantation 10: 258, 1970) and employs rat antigens as the immunological stimuli. Peripheral blood lymphocytes were injected into the hind feet of young Wistar rats, and 7 days later the popliteal lymph nodes were removed and weighed. It was found that the unwanted host-versus-graft activity could be suppressed in the rats by total body irradiation. Inactivated lymphocytes were injected into the right hind foot as a control and the result was expressed as a ratio: weight of left node to weight of right node. Lymphocytes from 45 healthy individuals were examined in this way. The response was readily suppressed by administering daily injections of steroid or antilymphocyte globulin to the rats, but was not influenced by the presence or absence of antirat antibodies in these individuals."}
{"id": "PMID:237356", "title": "[Karyosphere in oogenesis].", "content": "The purpose of this review is to draw attention to the peculiar phenomenon during gametogenesis: the formation of the karyosphere. This phenomenon is characterized by concentration of all chromosomes in the limited area of the nucleus and may be considered as alternative of the genome in the state of lumpbrush chromosomes. The formation of the karyosphere is a widely spread phenomenon during oogenesis of different animal classes. The karyosphere can be developed during different stages of oogenesis in different organisms; but as a rule the chromosomes of diploten stage of meiosis take part in its formation. As to functional identity of the karyosphere in different species, special investigations are to be done, but contemporary knowledge of the karyosphere formation reveals some common feature:1) in the karyosphere the chromosomes are in a relatively spiral state as demonstrated by the positive Feulgen reaction; 2) there is a low level of RNA synthesis or the absence of it in the karyosphere; 3) during the karyosphere formation the nucleus is enriched by the acid proteins and a lot of protein granules and structures appearing in a close contact with the karysphere. The more typical examples of the karyosphere formation can be observed in the insect oocytes belonging to the nutrimentary type of oogenesis. In the oocytes of some animals the peculiar protein substances are formed around the chromosome knot and appear as a fibrillar zone. Such karyosphere appears to be a kind of capsule inside the nucleus. The capsules are developed as a result of complex interaction between the main nuclear structures; chromosomes, nucleoli, and nuclear membrane as it is manifested by the analysis of some recent ultrastructural date obtained in some insect and amphibian oocytes. The function of the karyosphere capsule and the role of the nuclear structure (sinaptonemal complex, extrachromosomal DNA, and nuclear membrane) in formation of the capsule, are discussed as well as the ultrastructural and cytochemical similarity between the karyosphere capsule of oocytes and nuclear bodies of somatic cells.", "contents": "[Karyosphere in oogenesis]. The purpose of this review is to draw attention to the peculiar phenomenon during gametogenesis: the formation of the karyosphere. This phenomenon is characterized by concentration of all chromosomes in the limited area of the nucleus and may be considered as alternative of the genome in the state of lumpbrush chromosomes. The formation of the karyosphere is a widely spread phenomenon during oogenesis of different animal classes. The karyosphere can be developed during different stages of oogenesis in different organisms; but as a rule the chromosomes of diploten stage of meiosis take part in its formation. As to functional identity of the karyosphere in different species, special investigations are to be done, but contemporary knowledge of the karyosphere formation reveals some common feature:1) in the karyosphere the chromosomes are in a relatively spiral state as demonstrated by the positive Feulgen reaction; 2) there is a low level of RNA synthesis or the absence of it in the karyosphere; 3) during the karyosphere formation the nucleus is enriched by the acid proteins and a lot of protein granules and structures appearing in a close contact with the karysphere. The more typical examples of the karyosphere formation can be observed in the insect oocytes belonging to the nutrimentary type of oogenesis. In the oocytes of some animals the peculiar protein substances are formed around the chromosome knot and appear as a fibrillar zone. Such karyosphere appears to be a kind of capsule inside the nucleus. The capsules are developed as a result of complex interaction between the main nuclear structures; chromosomes, nucleoli, and nuclear membrane as it is manifested by the analysis of some recent ultrastructural date obtained in some insect and amphibian oocytes. The function of the karyosphere capsule and the role of the nuclear structure (sinaptonemal complex, extrachromosomal DNA, and nuclear membrane) in formation of the capsule, are discussed as well as the ultrastructural and cytochemical similarity between the karyosphere capsule of oocytes and nuclear bodies of somatic cells."}
{"id": "PMID:237357", "title": "[Effect of thymocytes on the quantity of polypotent hematopoietic mast cells in the spleen of sublethally irradiated mice].", "content": "With the aid of Till and McCulloch's method, 5 times 10(-6) thymic cells were found to cause an increase in the number of hemopoietic endogenous spleen colonies in syngeneic donor-recipient combination. Thymic cells of C57BL mice had no effect on the number of endogenous colonies in the spleen. 40 times 10(-6) thymic cells administered 24 hr after sublethal irradiation caused an increase in the number of colony forming units in the spleen within 14 days. Possible ways of the thymus effect on hemopoiesis are discussed.", "contents": "[Effect of thymocytes on the quantity of polypotent hematopoietic mast cells in the spleen of sublethally irradiated mice]. With the aid of Till and McCulloch's method, 5 times 10(-6) thymic cells were found to cause an increase in the number of hemopoietic endogenous spleen colonies in syngeneic donor-recipient combination. Thymic cells of C57BL mice had no effect on the number of endogenous colonies in the spleen. 40 times 10(-6) thymic cells administered 24 hr after sublethal irradiation caused an increase in the number of colony forming units in the spleen within 14 days. Possible ways of the thymus effect on hemopoiesis are discussed."}
{"id": "PMID:237358", "title": "Effect of human chorionic gonadotrophin on the dog seminiferous tubule, with and without experimental unilateral cryptorchism.", "content": "The effect on human chorionic gonadotrophin (HCG) on the testes of pubertal and postpubertal Beagle dogs was studied, in the one instance in bilaterally normotopic testes and in the other on the still scrotally located gonad of dogs which had been subjected to unilateral experimental cryptorchism. The area of the cross-sectioned seminiferous tubules served as a parameter for evaluating the effect of HCG. Administration of therapeutic doses of HCG produced, in animals with bilaterally normotopic testes, a marked diminution of the area of the seminiferous canals. This means that HCG application at normal dosage impairs the seminiferous tubules in the dog. In animals with unilateral cryptorchism, HCG application produced no significant change in the tubule area of the scrotally located testis beyond that which is ascertainable anyway on the orthotopic testis following translocation of the contralateral gonad to within the abdominal cavity. Hence, HCG does not influence the degenerative change in the orthotopic testis in experimental unilateral cryptorchism. Rather, an adverse effect of HCG on the seminiferous tubule is evident, independently of the hitherto published reports of successfully attained descent.", "contents": "Effect of human chorionic gonadotrophin on the dog seminiferous tubule, with and without experimental unilateral cryptorchism. The effect on human chorionic gonadotrophin (HCG) on the testes of pubertal and postpubertal Beagle dogs was studied, in the one instance in bilaterally normotopic testes and in the other on the still scrotally located gonad of dogs which had been subjected to unilateral experimental cryptorchism. The area of the cross-sectioned seminiferous tubules served as a parameter for evaluating the effect of HCG. Administration of therapeutic doses of HCG produced, in animals with bilaterally normotopic testes, a marked diminution of the area of the seminiferous canals. This means that HCG application at normal dosage impairs the seminiferous tubules in the dog. In animals with unilateral cryptorchism, HCG application produced no significant change in the tubule area of the scrotally located testis beyond that which is ascertainable anyway on the orthotopic testis following translocation of the contralateral gonad to within the abdominal cavity. Hence, HCG does not influence the degenerative change in the orthotopic testis in experimental unilateral cryptorchism. Rather, an adverse effect of HCG on the seminiferous tubule is evident, independently of the hitherto published reports of successfully attained descent."}
{"id": "PMID:237365", "title": "[Ornithine transcarbamylase in Clostridium perfingens].", "content": "Five strains of A type Cl. perfringens of different titres of toxicity (BP6K, SR-12, 2836, 2910, 1) possessed a distinct activity of ornithine transcarbamylase. In cells the maximal activity of the enzyme was observed within 3-5 hrs of growth of the culture. The enzyme was partially purified and some of its physico-chemical properties were studied. Ornithine transcarbamylase was termostable. Monoiodine acetate, p-chloromercurybenzoate, semicarbazide, Hg-2+, Cu-2+ and Fe-3+ inhibited the enzymatic activity, but Mg-2+ and Ca-2+ activated the enzyme. Ornithine transcarbamylase was shown to be active in wide region of pH: from pH 6.0 to pH 9.0 and higher. Two peaks of the enzyme activity were observed: the first (a more distinct one) at pH 8.6-8.9 and the second, smaller,--at pH 6.5-6.7.", "contents": "[Ornithine transcarbamylase in Clostridium perfingens]. Five strains of A type Cl. perfringens of different titres of toxicity (BP6K, SR-12, 2836, 2910, 1) possessed a distinct activity of ornithine transcarbamylase. In cells the maximal activity of the enzyme was observed within 3-5 hrs of growth of the culture. The enzyme was partially purified and some of its physico-chemical properties were studied. Ornithine transcarbamylase was termostable. Monoiodine acetate, p-chloromercurybenzoate, semicarbazide, Hg-2+, Cu-2+ and Fe-3+ inhibited the enzymatic activity, but Mg-2+ and Ca-2+ activated the enzyme. Ornithine transcarbamylase was shown to be active in wide region of pH: from pH 6.0 to pH 9.0 and higher. Two peaks of the enzyme activity were observed: the first (a more distinct one) at pH 8.6-8.9 and the second, smaller,--at pH 6.5-6.7."}
{"id": "PMID:237372", "title": "[Acid-base balance in the cerebrospinal fluid of normal subjects. Comparison of cisternal and lumbar CSF (author's transl)].", "content": "1. An investigation was carried out on 40 normal subjects of the acid-base balance in arterialized capillary blood and in the CSF (17 cisternal and 23 lumbar samples). The pH value was 7.324 in the cisternal CSF and 7.317 in the lumbar CSF, giving a difference of 0.007. The respective pCO2 values were 45.0 mm Hg and 45.9 mm Hg. The HCO3-minus value was 21.8 mMol/l, both in the cisternal and the lumbar CSF. 2. A comparison of the cisternal and lumbar CSF samples by means of the Wilcoxon-Mann-Whitney Test did not show any significant differences. 3. Neither of the groups showed a statistically significant dependence on age or sex. 4. Comparative studies by several authors of the acid-base balance in the cisternal and lumbar CSF are mentioned and discussed with reference to the present results.", "contents": "[Acid-base balance in the cerebrospinal fluid of normal subjects. Comparison of cisternal and lumbar CSF (author's transl)]. 1. An investigation was carried out on 40 normal subjects of the acid-base balance in arterialized capillary blood and in the CSF (17 cisternal and 23 lumbar samples). The pH value was 7.324 in the cisternal CSF and 7.317 in the lumbar CSF, giving a difference of 0.007. The respective pCO2 values were 45.0 mm Hg and 45.9 mm Hg. The HCO3-minus value was 21.8 mMol/l, both in the cisternal and the lumbar CSF. 2. A comparison of the cisternal and lumbar CSF samples by means of the Wilcoxon-Mann-Whitney Test did not show any significant differences. 3. Neither of the groups showed a statistically significant dependence on age or sex. 4. Comparative studies by several authors of the acid-base balance in the cisternal and lumbar CSF are mentioned and discussed with reference to the present results."}
{"id": "PMID:237391", "title": "Changes in systolic time intervals during stepwise increasing hypoxia.", "content": "Determinations of the reciprocal value of the square of the pre-ejection period (1/PEP-2) and the pre-ejection period/left ventricular ejection time-ratio (PEP/LVET-ratio) during stepwise increasing hypoxia showed in seven mongrel dogs in a decrease in PEP/LVET-ratio and an increase in 1/PEP-2 as an expression of a stimulation of the cardiac function. Significant changes were not observed before the arterial oxygen tension (Pao2) was below 40 mmHg. During severe hypoxia (Pao2 15-20 mmHg), some deterioration in the systolic time intervals occurs with time, but a stimulation persists at the time of death compared to the prehypoxic values.", "contents": "Changes in systolic time intervals during stepwise increasing hypoxia. Determinations of the reciprocal value of the square of the pre-ejection period (1/PEP-2) and the pre-ejection period/left ventricular ejection time-ratio (PEP/LVET-ratio) during stepwise increasing hypoxia showed in seven mongrel dogs in a decrease in PEP/LVET-ratio and an increase in 1/PEP-2 as an expression of a stimulation of the cardiac function. Significant changes were not observed before the arterial oxygen tension (Pao2) was below 40 mmHg. During severe hypoxia (Pao2 15-20 mmHg), some deterioration in the systolic time intervals occurs with time, but a stimulation persists at the time of death compared to the prehypoxic values."}
{"id": "PMID:237392", "title": "Effects of general anaesthetics on the pH of gastric contents in man during surgery: a survey of halothane, fluoroxene and cyclopropane anesthesia.", "content": "The effect of premedication and three general anaesthetics on gastric content pH was investigated. Neither premedication with pentobarbital-atropine nor morphine-scopolamine given 1-2 h prior to anaesthesia appeared to affect the acidity of the gastric contents. Halothane invaribly increased the pH of the gastric contents; none of the seven patients studied had a gastric pH of less than 2.5 (mean 5.1) after 1 h of anesthesia. Cyclopropane uniformly maintained the acidity of the gastric contents; only one out of seven patients had a gastric content pH above 2.5 (mean 1.7) after 1 h of anaesthesia. This effect of cyclopropane in maintaining the pH of gastric contents was unaffected by the use of premedication and induction with thiopental. Fluorexene affected the pH of the gastric contents much less uniformly. Although the pH for the group as a whole gradually increased (after one hour from 1.7 plus or minus 0.2 (s.e. mean) to 3.1 plus or minus 0.7), some of the seven patients studied reacted to fluroxene with a constant low gastric content pH. The findings are discussed, and it is concluded that the risk of pulmonary complications in case of vomiting and aspiration upon emergence from anaesthesia is greater if the anaesthetic agent is cyclopropane or fluoroxene, than if it is halothane.", "contents": "Effects of general anaesthetics on the pH of gastric contents in man during surgery: a survey of halothane, fluoroxene and cyclopropane anesthesia. The effect of premedication and three general anaesthetics on gastric content pH was investigated. Neither premedication with pentobarbital-atropine nor morphine-scopolamine given 1-2 h prior to anaesthesia appeared to affect the acidity of the gastric contents. Halothane invaribly increased the pH of the gastric contents; none of the seven patients studied had a gastric pH of less than 2.5 (mean 5.1) after 1 h of anesthesia. Cyclopropane uniformly maintained the acidity of the gastric contents; only one out of seven patients had a gastric content pH above 2.5 (mean 1.7) after 1 h of anaesthesia. This effect of cyclopropane in maintaining the pH of gastric contents was unaffected by the use of premedication and induction with thiopental. Fluorexene affected the pH of the gastric contents much less uniformly. Although the pH for the group as a whole gradually increased (after one hour from 1.7 plus or minus 0.2 (s.e. mean) to 3.1 plus or minus 0.7), some of the seven patients studied reacted to fluroxene with a constant low gastric content pH. The findings are discussed, and it is concluded that the risk of pulmonary complications in case of vomiting and aspiration upon emergence from anaesthesia is greater if the anaesthetic agent is cyclopropane or fluoroxene, than if it is halothane."}
{"id": "PMID:237393", "title": "Prostaglandin F2 alfa infusion and halothane anaesthesia.", "content": "The cardiovascular reaction to infusion of prostaglandin F2 alfa was examined in seven patients during N2O-jalothane anaesthesia. As in the non-anaesthetized individual, no changes in blood pressure, pulse rate, CVP or ECG occurred during anaesthesia, but a great reflux of enteric juice to the ventricle was noticed only 2-3 min after the beginning of the hormone infusion. It is concluded that prostaglandin F2 alfa may be safely given to patients who are going to be anaesthetized, but the patients must be considered as having a full stomach and therefore treated as such.", "contents": "Prostaglandin F2 alfa infusion and halothane anaesthesia. The cardiovascular reaction to infusion of prostaglandin F2 alfa was examined in seven patients during N2O-jalothane anaesthesia. As in the non-anaesthetized individual, no changes in blood pressure, pulse rate, CVP or ECG occurred during anaesthesia, but a great reflux of enteric juice to the ventricle was noticed only 2-3 min after the beginning of the hormone infusion. It is concluded that prostaglandin F2 alfa may be safely given to patients who are going to be anaesthetized, but the patients must be considered as having a full stomach and therefore treated as such."}
{"id": "PMID:237394", "title": "Cardiac function during halothane anf fluroxene anesthesia expressed by systolic time intervals.", "content": "A non-invasive method of measuring the systolic time intervals (STI) during anesthesia is described. Using the ratio between the pre-ejection period and the left ventricular ejection time (PEP/LVET-ratio) as an expression of cardiac function, it is shown in 39 patients that thiopentone exerted a marked depression on the heart (increase in PEP/LVET-ratio). This depression was further aggravated by halothane, while fluroxene caused an improvement of PEP/LVET-ratio. In the immediate post-anesthetic period PEP/LVET-ratio almost reached control value after discontinuation of fluroxene in contrast to halothane, where an increased PEP/LVET-ratio (25%) still persisted. The changes were mainly due to a prolongation of PEP without any specific change in LVET. During the study, PEP/LVET-ratio showed a close correlation to the reciprocal value of the square of the pre-ejection period (1/PEP-2). STI form 27 volunteers were measured and compared to the values from the patients before anesthesia was induced. PEP and PEP/LVET-ratio were significantly shorter in the patient group.", "contents": "Cardiac function during halothane anf fluroxene anesthesia expressed by systolic time intervals. A non-invasive method of measuring the systolic time intervals (STI) during anesthesia is described. Using the ratio between the pre-ejection period and the left ventricular ejection time (PEP/LVET-ratio) as an expression of cardiac function, it is shown in 39 patients that thiopentone exerted a marked depression on the heart (increase in PEP/LVET-ratio). This depression was further aggravated by halothane, while fluroxene caused an improvement of PEP/LVET-ratio. In the immediate post-anesthetic period PEP/LVET-ratio almost reached control value after discontinuation of fluroxene in contrast to halothane, where an increased PEP/LVET-ratio (25%) still persisted. The changes were mainly due to a prolongation of PEP without any specific change in LVET. During the study, PEP/LVET-ratio showed a close correlation to the reciprocal value of the square of the pre-ejection period (1/PEP-2). STI form 27 volunteers were measured and compared to the values from the patients before anesthesia was induced. PEP and PEP/LVET-ratio were significantly shorter in the patient group."}
{"id": "PMID:237395", "title": "Effects of respiratory acidosis on the arrhythmia threshold during fluroxene and halothane anesthesia.", "content": "Hypercarbia was induced in 12 patients anesthetized with either halothane or fluroxene in an inspired concentration of approximately 1.3 MAC (1% halothane and 4-5% fluroxene). The six patients receiving halothane anesthesia responded to hypercarbia with a pronounced tachycardia, an increased arterial pressure and an electrocardiographically monitored threshold level for ventricular arrhythmias at a Paco2 level averaging 98 mmHg. The six patients receiving fluroxene anesthesia responded to hypercarbia with both tachycardia and hypertension, but in spite of an average Paco2 level of 109 mmHg, no ventricular arrhythmias could be provoked. It is therefore suggested that within the non-narcotic level of hypercarbia a threshold level for cardiac arrhythmias does not exist under fluroxene anesthesia.", "contents": "Effects of respiratory acidosis on the arrhythmia threshold during fluroxene and halothane anesthesia. Hypercarbia was induced in 12 patients anesthetized with either halothane or fluroxene in an inspired concentration of approximately 1.3 MAC (1% halothane and 4-5% fluroxene). The six patients receiving halothane anesthesia responded to hypercarbia with a pronounced tachycardia, an increased arterial pressure and an electrocardiographically monitored threshold level for ventricular arrhythmias at a Paco2 level averaging 98 mmHg. The six patients receiving fluroxene anesthesia responded to hypercarbia with both tachycardia and hypertension, but in spite of an average Paco2 level of 109 mmHg, no ventricular arrhythmias could be provoked. It is therefore suggested that within the non-narcotic level of hypercarbia a threshold level for cardiac arrhythmias does not exist under fluroxene anesthesia."}
{"id": "PMID:237396", "title": "The influence of arterial carbon dioxide tension on the cerebrovascular response to arterial hypoxia and to haemodilution.", "content": "Cerebral blood flow (CBF) measurements and blood gas analyses were performed on anaesthetized and artifically ventilated dogs during arterial hypoxia or haemodilution in different ranges of arterial carbon dioxide tension. Arterial hypoxia as well as haemodilution produced a flow increase in all ranges of ventilation. However, this flow increase was elicited at a cerebrovenous oxygen tension which rose with the arterial carbon dioxide tension, but which tended to be maintained by the flow increase during continued decrease of the arterial oxygen content. On the assumption that the cerebrovenous oxygen tension reflects the oxygen tension of the brain tissue, it is suggested that the arterial carbon dioxide tension influences the ability of the brain tissue to maintain the aerobic metabolism during reduced tissue oxygen tension. This means that tissue hypoxia, in the sense of utilisation of anaerobic metabolism, occurs at a tissue oxygen tension which is lower the lower the arterial carbon dioxide tension is.", "contents": "The influence of arterial carbon dioxide tension on the cerebrovascular response to arterial hypoxia and to haemodilution. Cerebral blood flow (CBF) measurements and blood gas analyses were performed on anaesthetized and artifically ventilated dogs during arterial hypoxia or haemodilution in different ranges of arterial carbon dioxide tension. Arterial hypoxia as well as haemodilution produced a flow increase in all ranges of ventilation. However, this flow increase was elicited at a cerebrovenous oxygen tension which rose with the arterial carbon dioxide tension, but which tended to be maintained by the flow increase during continued decrease of the arterial oxygen content. On the assumption that the cerebrovenous oxygen tension reflects the oxygen tension of the brain tissue, it is suggested that the arterial carbon dioxide tension influences the ability of the brain tissue to maintain the aerobic metabolism during reduced tissue oxygen tension. This means that tissue hypoxia, in the sense of utilisation of anaerobic metabolism, occurs at a tissue oxygen tension which is lower the lower the arterial carbon dioxide tension is."}
{"id": "PMID:237397", "title": "Acid-base and electrolyte balance in infants of diabetic mothers. Vaginal delivery versus caesarean section.", "content": "The acid-base and electrolyte balance of 30 women studied at delivery and in their infants during the first 48 h. 18 women were diabetics, 10 of these were delivered vaginally (DMvag) and 8 by elective caesarean section (DMcs). 12 healthy women were vaginally delivered (HMvag). The infants of diabetic mothers (IDM) received active infusion therapy. At birth the DMvag and their infants (IDMvag) had a more pronounced metabolic acidosis than the DMcs and their babies (IDMcs). The largest metabolic acidosis occurred, however, in the group of HMvag and their infants (IHMvag). After birth no significant differences were obtained in the acid-base and electrolyte balance between IDMvag and IDMcs. The plasma potassium level remained lower in IDM than in IHM. The study stress the importance of adequate management of diabetes in pregnancy in combination with active intravenous therapy during delivery and to the infant in the immediate neonatal period. The slightly larger metabolic acidosis seen in combination with vaginal delivery suggests that this mode of delivery should not be attempted uncritically in diabetic women.", "contents": "Acid-base and electrolyte balance in infants of diabetic mothers. Vaginal delivery versus caesarean section. The acid-base and electrolyte balance of 30 women studied at delivery and in their infants during the first 48 h. 18 women were diabetics, 10 of these were delivered vaginally (DMvag) and 8 by elective caesarean section (DMcs). 12 healthy women were vaginally delivered (HMvag). The infants of diabetic mothers (IDM) received active infusion therapy. At birth the DMvag and their infants (IDMvag) had a more pronounced metabolic acidosis than the DMcs and their babies (IDMcs). The largest metabolic acidosis occurred, however, in the group of HMvag and their infants (IHMvag). After birth no significant differences were obtained in the acid-base and electrolyte balance between IDMvag and IDMcs. The plasma potassium level remained lower in IDM than in IHM. The study stress the importance of adequate management of diabetes in pregnancy in combination with active intravenous therapy during delivery and to the infant in the immediate neonatal period. The slightly larger metabolic acidosis seen in combination with vaginal delivery suggests that this mode of delivery should not be attempted uncritically in diabetic women."}
{"id": "PMID:237409", "title": "Correlation between blood gases, glycolytic enzymes and EEG during electroconvulsive treatment in relaxation.", "content": "Twenty-three psychiatric patients were investigated during electroconvulsive treatment in relaxation. The blood gases, pH and serum bicarbonate levels in blood samples from the internal jugular vein and the femoral artery were measured radiometrically. The LDH fractions were separated electrophoretically and their activity, along with the activity of aldolase, was then determined on test materials. EEG recordings were made during the seizure and also during postconvulsive restitution. The following conclusions were drawn: (1) There was no evidence of anoxic anoxia in the brain during and after seizures. (2) A close relationship was found between the corresponding phases of electrical activity and brain metabolism as indicated by the blood gas changes during postconvulsive restitution. (3) On the basis of the increased glycolytic activity in the sera it is probable that glucose metabolism was shifted in the anaerobic direction during postconvulsive restitution of the brain tissues.", "contents": "Correlation between blood gases, glycolytic enzymes and EEG during electroconvulsive treatment in relaxation. Twenty-three psychiatric patients were investigated during electroconvulsive treatment in relaxation. The blood gases, pH and serum bicarbonate levels in blood samples from the internal jugular vein and the femoral artery were measured radiometrically. The LDH fractions were separated electrophoretically and their activity, along with the activity of aldolase, was then determined on test materials. EEG recordings were made during the seizure and also during postconvulsive restitution. The following conclusions were drawn: (1) There was no evidence of anoxic anoxia in the brain during and after seizures. (2) A close relationship was found between the corresponding phases of electrical activity and brain metabolism as indicated by the blood gas changes during postconvulsive restitution. (3) On the basis of the increased glycolytic activity in the sera it is probable that glucose metabolism was shifted in the anaerobic direction during postconvulsive restitution of the brain tissues."}
{"id": "PMID:237410", "title": "The automated assessment of the effect of flurazepam and nitrazepam on mood state.", "content": "Some further results on the effects of the two hypnotic drugs, nitrazepam and flurazepam monohydrochloride, on mood state are described. An automated assessment and scoring system, Computer Assisted Psychometric System (C.A.P.S.), was used to assess mood state and showed that both hypnotics had a mild euphoriant effect even when administered to healthy volunteers during the daytime. This was most marked in the case of nitrazepam. It is argued that such euphoriant side effects should be further investigated as they can occur when hypnotics are administered on a long-term nightly basis, and there may therefore be a dependency aspect for those patients who habitually take such hypnotic drugs. The broad scope of the C.A.P.S. system is also discussed.", "contents": "The automated assessment of the effect of flurazepam and nitrazepam on mood state. Some further results on the effects of the two hypnotic drugs, nitrazepam and flurazepam monohydrochloride, on mood state are described. An automated assessment and scoring system, Computer Assisted Psychometric System (C.A.P.S.), was used to assess mood state and showed that both hypnotics had a mild euphoriant effect even when administered to healthy volunteers during the daytime. This was most marked in the case of nitrazepam. It is argued that such euphoriant side effects should be further investigated as they can occur when hypnotics are administered on a long-term nightly basis, and there may therefore be a dependency aspect for those patients who habitually take such hypnotic drugs. The broad scope of the C.A.P.S. system is also discussed."}
{"id": "PMID:237415", "title": "Hemodynamic effects of slow and rapid defibrination with defibrizyme, the thrombin-like enzyme from venom of the timber rattlesnake.", "content": "The hemodynamic response to slow and rapid defibrination was sutdied in anesthetized beagle dogs, with the following results: 1. Slow defibrination was a benign procedure that had little or no effect on the hemodynamic variables studied. 2. Rapid defibrination induced statistically significant decreases in cardiac output, stroke volume, and mean aortic arterial pressure. 3. Bradycardia, a drop in mean left v\"ntricular pressure, cardiac and minute work indices, an increase in pulmonary artery pressure, and a drastic rise in pulmonary and systemic vascular resistances were also observed. Although physiologically apparent, these changes were not statistically significantly different from control levels. 4. Pulmonary capillary wedge pressure, left ventricular end-disatolic pressure, arterial pH, and blood gases were not altered by rapid defibrination. 5. In view of the similarities between the hemodynamic changes observed after rapid defibrination and acute myocardial ischemia, the role of decreasing fibrinogen concentrations and blood viscosity in aucte myocardial infarction and the sudden death syndrome is questioned.", "contents": "Hemodynamic effects of slow and rapid defibrination with defibrizyme, the thrombin-like enzyme from venom of the timber rattlesnake. The hemodynamic response to slow and rapid defibrination was sutdied in anesthetized beagle dogs, with the following results: 1. Slow defibrination was a benign procedure that had little or no effect on the hemodynamic variables studied. 2. Rapid defibrination induced statistically significant decreases in cardiac output, stroke volume, and mean aortic arterial pressure. 3. Bradycardia, a drop in mean left v\"ntricular pressure, cardiac and minute work indices, an increase in pulmonary artery pressure, and a drastic rise in pulmonary and systemic vascular resistances were also observed. Although physiologically apparent, these changes were not statistically significantly different from control levels. 4. Pulmonary capillary wedge pressure, left ventricular end-disatolic pressure, arterial pH, and blood gases were not altered by rapid defibrination. 5. In view of the similarities between the hemodynamic changes observed after rapid defibrination and acute myocardial ischemia, the role of decreasing fibrinogen concentrations and blood viscosity in aucte myocardial infarction and the sudden death syndrome is questioned."}
{"id": "PMID:237416", "title": "In line final filters for removing particles from amphotericin B infusions.", "content": "The feasibility of using membrane filters to remove particles from intravenous infusions of amphotericin B in dextrose 5% (a colloidal solution) was studied. Six types of commercial membrane filters, ranging in pore size from 0.45-1.0 mum, were used. Because of the effect of pH on the particle size of colloidal solutions, each filter was tested at solution pH 4.7, 5.6 and 6.5. Samples of filtrate were analyzed spectrophotometrically for amphotericin content. All filters of pore size 0.22 mum removed amphotericin B from solution and were inappropriate for use with this product. Solutions at pH 4.7 were turbid, filtered slowly and were generally unacceptable for clinical use. At pH 5.6, only filters with pore sizes of 1.0 mum or greater showed acceptable results. At pH 6.5, filters with pore sizes of 0.45 mum or greater gave acceptable results; the use of a filter with a pore size of not less than 1.0 mum would provide a margin for error to compensate for variations in the colloidal particle size of amphotericin B.", "contents": "In line final filters for removing particles from amphotericin B infusions. The feasibility of using membrane filters to remove particles from intravenous infusions of amphotericin B in dextrose 5% (a colloidal solution) was studied. Six types of commercial membrane filters, ranging in pore size from 0.45-1.0 mum, were used. Because of the effect of pH on the particle size of colloidal solutions, each filter was tested at solution pH 4.7, 5.6 and 6.5. Samples of filtrate were analyzed spectrophotometrically for amphotericin content. All filters of pore size 0.22 mum removed amphotericin B from solution and were inappropriate for use with this product. Solutions at pH 4.7 were turbid, filtered slowly and were generally unacceptable for clinical use. At pH 5.6, only filters with pore sizes of 1.0 mum or greater showed acceptable results. At pH 6.5, filters with pore sizes of 0.45 mum or greater gave acceptable results; the use of a filter with a pore size of not less than 1.0 mum would provide a margin for error to compensate for variations in the colloidal particle size of amphotericin B."}
{"id": "PMID:237420", "title": "Drug therapy in terminally ill patients.", "content": "The drug treatment of terminally ill patients is reviewed. The treatment of the major discomforting symptoms of degenerative diseases--pain, anxiety, nausea, vomiting and depression--is reviewed. The use of phenothiazines, anticholinergic drugs and corticosteroids is discussed. To help patients keep track of their drugs, use of a medication schedule card is recommended.", "contents": "Drug therapy in terminally ill patients. The drug treatment of terminally ill patients is reviewed. The treatment of the major discomforting symptoms of degenerative diseases--pain, anxiety, nausea, vomiting and depression--is reviewed. The use of phenothiazines, anticholinergic drugs and corticosteroids is discussed. To help patients keep track of their drugs, use of a medication schedule card is recommended."}
{"id": "PMID:237423", "title": "Clinical neuromuscular pharmacology of AH 8165 D, an azobis-arylimidazo-pyridinium-compound.", "content": "The neuromuscular blocking properties of AH 8165 D (1,1'azobis-(3-methyl-2-phenyl-1H-imidazo-1,2a-pyridinium)dibromide) were quantitatively studied in 50 patients, undergoing extra-abdominal surgery and anaesthetized with barbiturates, nitrous oxide, fentanyl and droperidol, by means of mechanograms of the hand muscles obtained by ulnar nerve stimulation. AH 8165 D is a rapid-acting nondepolarizing agent (full effect within 1--2 min) providing good intubation conditions similar to those obtained with suxamethonium. AH 8165 D may be considered to be indicated for emergency intubation in patients with full stomach when the risk of regurgitation is high. The duration of action of clinically useful doses (0.4-0.8 mg/kg body weight) is shorter than that of equi-effective doses of other nondepolarizing muscle relaxants. Repeated doses show a cumulative effect. The neuromuscular blockade can easily be reversed by an anticholinesterase drug. AH 8165 D-induced muscle relaxation is always accompanied by a dose-dependent tachycardia limiting the clinical usefulness of this new drug.", "contents": "Clinical neuromuscular pharmacology of AH 8165 D, an azobis-arylimidazo-pyridinium-compound. The neuromuscular blocking properties of AH 8165 D (1,1'azobis-(3-methyl-2-phenyl-1H-imidazo-1,2a-pyridinium)dibromide) were quantitatively studied in 50 patients, undergoing extra-abdominal surgery and anaesthetized with barbiturates, nitrous oxide, fentanyl and droperidol, by means of mechanograms of the hand muscles obtained by ulnar nerve stimulation. AH 8165 D is a rapid-acting nondepolarizing agent (full effect within 1--2 min) providing good intubation conditions similar to those obtained with suxamethonium. AH 8165 D may be considered to be indicated for emergency intubation in patients with full stomach when the risk of regurgitation is high. The duration of action of clinically useful doses (0.4-0.8 mg/kg body weight) is shorter than that of equi-effective doses of other nondepolarizing muscle relaxants. Repeated doses show a cumulative effect. The neuromuscular blockade can easily be reversed by an anticholinesterase drug. AH 8165 D-induced muscle relaxation is always accompanied by a dose-dependent tachycardia limiting the clinical usefulness of this new drug."}
{"id": "PMID:237424", "title": "Light- and electron microscopic investigations of pulmonary tissue after high-frequency positive-pressure ventilation (HFPPV).", "content": "Narcotisized dogs were artificially ventilated for periods of two to five hours with HFPPV. During this time the blood gases, pH and bases were controlled. In spite of sufficient oxygenation and CO2-elimination, a metabolic acidosis developed which could not be fully compensated by the addition of buffer solutions. In light and electron microscopy these lungs did not differ significantly from control lungs. Haemorrhages or atelectases were never observed. Type I cells as well as Type II cells in the alveoli are unchanged, i.e. the Type II cells were not depleted but contained numerous typical lamellar bodies with a diameter of 0.4-1 mu. The blood gas barrier was not widened and was ca. 3000 A wide. The alveolar surface was coated by an often fragmented electron-dense film (monolayer of the surfactant).", "contents": "Light- and electron microscopic investigations of pulmonary tissue after high-frequency positive-pressure ventilation (HFPPV). Narcotisized dogs were artificially ventilated for periods of two to five hours with HFPPV. During this time the blood gases, pH and bases were controlled. In spite of sufficient oxygenation and CO2-elimination, a metabolic acidosis developed which could not be fully compensated by the addition of buffer solutions. In light and electron microscopy these lungs did not differ significantly from control lungs. Haemorrhages or atelectases were never observed. Type I cells as well as Type II cells in the alveoli are unchanged, i.e. the Type II cells were not depleted but contained numerous typical lamellar bodies with a diameter of 0.4-1 mu. The blood gas barrier was not widened and was ca. 3000 A wide. The alveolar surface was coated by an often fragmented electron-dense film (monolayer of the surfactant)."}
{"id": "PMID:237444", "title": "Transmission of hog hog cholera virus by mosquitoes.", "content": "Mosquitoes trapped during an epizootic of hog cholera (HC) in Maryland in 1969 were prepared into 40 pools which were inoculated in pigs. Hog cholera virus was confirmed in pigs inoculated with 8 of 40 pools of mosquitoes. Generally, the pigs contracting HC developed chronic infections with persistent viremia that lasted 30 or more days. Two pigs seemed healthy when euthatized 62 and 80 days after inoculation, yet viremia of high titer was detected in each. Experimental studies were performed with 2 laboratory strains of mosquitoes, Aedes aegypti and Culex tarsalis, to determine if biological and mechanical transmission occur. Biological transmission was not confirmed, but HC virus was retained in A aegypti for 3 days. Mechanical transmission was confirmed with A aegypti in 2 of 9 experiments.", "contents": "Transmission of hog hog cholera virus by mosquitoes. Mosquitoes trapped during an epizootic of hog cholera (HC) in Maryland in 1969 were prepared into 40 pools which were inoculated in pigs. Hog cholera virus was confirmed in pigs inoculated with 8 of 40 pools of mosquitoes. Generally, the pigs contracting HC developed chronic infections with persistent viremia that lasted 30 or more days. Two pigs seemed healthy when euthatized 62 and 80 days after inoculation, yet viremia of high titer was detected in each. Experimental studies were performed with 2 laboratory strains of mosquitoes, Aedes aegypti and Culex tarsalis, to determine if biological and mechanical transmission occur. Biological transmission was not confirmed, but HC virus was retained in A aegypti for 3 days. Mechanical transmission was confirmed with A aegypti in 2 of 9 experiments."}
{"id": "PMID:237446", "title": "Exit of Anaplasma marginale from bovine red blood cells.", "content": "Incubation of Anaplasma marginale-infected bovine red blood cells in a flow culture system resulted in a decrease of observable marginal bodies. The decrease was twice the degree of hemolysis, indicating that marginal bodies may leave red blood cells without concomitant lysis of the host cell.", "contents": "Exit of Anaplasma marginale from bovine red blood cells. Incubation of Anaplasma marginale-infected bovine red blood cells in a flow culture system resulted in a decrease of observable marginal bodies. The decrease was twice the degree of hemolysis, indicating that marginal bodies may leave red blood cells without concomitant lysis of the host cell."}
{"id": "PMID:237445", "title": "Experimentally induced intestinal obstruction in sheep: paradoxical aciduria in metabolic alkalosis.", "content": "Ewes with surgically prepared obstruction of the duodenum were used as a model in the study of ruminant metabolic alkalosis and paradoxical aciduria. Metabolic alkalosis occurred as a result of irreversible chloride loss, presumably into the abomasum and forestomachs. Analysis of data on serum and urinary electrolye concentrations provided limited support for the explanation of paradoxical aciduria in terms of chloride and potassium deficiencies. The accumulation undetermined anions in the serum indicated that the decreased urinary pH was due to the excretion of titratable acid.", "contents": "Experimentally induced intestinal obstruction in sheep: paradoxical aciduria in metabolic alkalosis. Ewes with surgically prepared obstruction of the duodenum were used as a model in the study of ruminant metabolic alkalosis and paradoxical aciduria. Metabolic alkalosis occurred as a result of irreversible chloride loss, presumably into the abomasum and forestomachs. Analysis of data on serum and urinary electrolye concentrations provided limited support for the explanation of paradoxical aciduria in terms of chloride and potassium deficiencies. The accumulation undetermined anions in the serum indicated that the decreased urinary pH was due to the excretion of titratable acid."}
{"id": "PMID:237447", "title": "Impact of physician's assistants on patient visits in ambulatory care practices.", "content": "The addition of a physician's assistant to an ambulatory care practice increases the practice's productivity. Practices using physician's assistants (medexes) had a 12% increase in the number of patient visits during the first year of training and 1 3/4 years later had an average increase of 37%. The medex by himself provided care to 28% of the patients and, in company with the physician, to another 10%. No consistent changes across practices were noted in patient waiting times or time physicians spend with patients.", "contents": "Impact of physician's assistants on patient visits in ambulatory care practices. The addition of a physician's assistant to an ambulatory care practice increases the practice's productivity. Practices using physician's assistants (medexes) had a 12% increase in the number of patient visits during the first year of training and 1 3/4 years later had an average increase of 37%. The medex by himself provided care to 28% of the patients and, in company with the physician, to another 10%. No consistent changes across practices were noted in patient waiting times or time physicians spend with patients."}
{"id": "PMID:237448", "title": "Cephalothin and cephaloridine therapy for bacterial meningitis.", "content": "The efficacy of cephalothin and cephaloridine in the treatment of bacterial meningitis was evaluated from a review of 106 cases reported in the literature. Fifty-nine percent of 34 patients treated with intravenous cephalothin responded suboptimally; those receiving daily doses of 12 g or more fared significantly better (P less than 0.025). In contrast, 74% of 72 patients treated with cephaloridine responded favorably; those who received concomitant intrathecal cephaloridine responded significantly better (P less than 0.005). These findings indicate that cephalosporin therapy for bacterial meningitis, without concomitant intrathecal medication, is unreliable and that this is probably due to inadequate penetration of the antibiotics into cerebrospinal fluid. In penicillin-allergic patients with pneumococcal, meningococcal, and hemophilus meningitis, chloramphenicol is the agent of choice. For staphylococcal meningitis, intravenous cephalothin at doses of 12 g/day with additional intrathecal cephaloridine at doses of 12.5 to 50 mg/day should be administered concomitantly.", "contents": "Cephalothin and cephaloridine therapy for bacterial meningitis. The efficacy of cephalothin and cephaloridine in the treatment of bacterial meningitis was evaluated from a review of 106 cases reported in the literature. Fifty-nine percent of 34 patients treated with intravenous cephalothin responded suboptimally; those receiving daily doses of 12 g or more fared significantly better (P less than 0.025). In contrast, 74% of 72 patients treated with cephaloridine responded favorably; those who received concomitant intrathecal cephaloridine responded significantly better (P less than 0.005). These findings indicate that cephalosporin therapy for bacterial meningitis, without concomitant intrathecal medication, is unreliable and that this is probably due to inadequate penetration of the antibiotics into cerebrospinal fluid. In penicillin-allergic patients with pneumococcal, meningococcal, and hemophilus meningitis, chloramphenicol is the agent of choice. For staphylococcal meningitis, intravenous cephalothin at doses of 12 g/day with additional intrathecal cephaloridine at doses of 12.5 to 50 mg/day should be administered concomitantly."}
{"id": "PMID:237450", "title": "Theophylline-induced seizures in adults. Correlation with serum concentrations.", "content": "Eight patients developed grand mal seizures during intravenous theophylline therapy. None had a history of neurologic disorder, and all were acutely ill with severe pulmonary or cardiovascular disease, or both. Serum theophylline concentrations obtained within 1 hour of the seizure ranged from 25 mug/ml to 70mug/ml, with a mean value (53 plus or minus 4.8 mug/ml) more than twice the upper limit of the recommended therapeutic concentration. This serum theophylline concentration was greater than the concentration found in a group  of patients with less severe drug-related symptoms (35 plus or minus 1.8 mug/ml, P less than 0.01). A third group of patients without drug-related symptoms had a mean theophylline serum concentration of 19 plus or minus 2.0 mug/ml, which was less than that found in either group with toxicity symptoms (P less than 0.05). Factors predisposing to the high serum concentrations in the patients with seizures were both higher drug dosage, compared with the other groups (P less than 0.01), and hepatic dysfunction, which was more common in both groups with drug-related symptoms.", "contents": "Theophylline-induced seizures in adults. Correlation with serum concentrations. Eight patients developed grand mal seizures during intravenous theophylline therapy. None had a history of neurologic disorder, and all were acutely ill with severe pulmonary or cardiovascular disease, or both. Serum theophylline concentrations obtained within 1 hour of the seizure ranged from 25 mug/ml to 70mug/ml, with a mean value (53 plus or minus 4.8 mug/ml) more than twice the upper limit of the recommended therapeutic concentration. This serum theophylline concentration was greater than the concentration found in a group  of patients with less severe drug-related symptoms (35 plus or minus 1.8 mug/ml, P less than 0.01). A third group of patients without drug-related symptoms had a mean theophylline serum concentration of 19 plus or minus 2.0 mug/ml, which was less than that found in either group with toxicity symptoms (P less than 0.05). Factors predisposing to the high serum concentrations in the patients with seizures were both higher drug dosage, compared with the other groups (P less than 0.01), and hepatic dysfunction, which was more common in both groups with drug-related symptoms."}
{"id": "PMID:237451", "title": "Lactic acidosis from carboxyhemoglobinemia after smoke inhalation.", "content": "Tissue hypoxia as a result of a wide variety of clinical situations had frequently been implicated as a cause of systemic acidosis due to the accumulation of lactic acid. Four patients suffering from smoke inhalation had lactic acidosis in association with carboxyhemoglobinemia. There was no evidence of decreased tissue perfusion, hypotension, arterial hypoxemia, or anemia. The following were tested in all patients: arterial pH (7.25 to 7.40), Pco-2 (19 to 27 mm Hg), Po (63 to 116 mm Hg), HCO-2- (11 to 19 meq/litre), carboxyhemoglobin (13% to 37%), and lactic acid (5.1 to 9.3 meq/litre). After therapy with oxygen and intravenous corticosteroids, there was prompt return of lactic acid levels, carboxyhemoglobin values, and arterial pH to normal. It is concluded that the cause of lactic acidosis in the presence of carboxyhemoglobinemia during smoke inhalation is tissue hypoxia. This tissue hypoxia is due to the reduction of the oxygen-carrying capacity of the blood and the concomitant shift of the oxyhemoglobin dissociation curve to the left, both known to result from carboxyhemoglobinemia.", "contents": "Lactic acidosis from carboxyhemoglobinemia after smoke inhalation. Tissue hypoxia as a result of a wide variety of clinical situations had frequently been implicated as a cause of systemic acidosis due to the accumulation of lactic acid. Four patients suffering from smoke inhalation had lactic acidosis in association with carboxyhemoglobinemia. There was no evidence of decreased tissue perfusion, hypotension, arterial hypoxemia, or anemia. The following were tested in all patients: arterial pH (7.25 to 7.40), Pco-2 (19 to 27 mm Hg), Po (63 to 116 mm Hg), HCO-2- (11 to 19 meq/litre), carboxyhemoglobin (13% to 37%), and lactic acid (5.1 to 9.3 meq/litre). After therapy with oxygen and intravenous corticosteroids, there was prompt return of lactic acid levels, carboxyhemoglobin values, and arterial pH to normal. It is concluded that the cause of lactic acidosis in the presence of carboxyhemoglobinemia during smoke inhalation is tissue hypoxia. This tissue hypoxia is due to the reduction of the oxygen-carrying capacity of the blood and the concomitant shift of the oxyhemoglobin dissociation curve to the left, both known to result from carboxyhemoglobinemia."}
{"id": "PMID:237459", "title": "Bicycle and moped spoke injuries in children. Analysis of 103 consecutive cases.", "content": "The series consists of 60 boys and 43 girls, aged from 1 to 14 years, mean 4.95 years, whose right (42) or left (61) foot was caught between the bicycle (97) or moped (6) spokes. The skin was involved with ankle sprain, with fracture or without other injuries in 97 children; lateral aspect of the ankle and foot in 65 and heel in 21 patients. The X-rays revealed 10 tibial fractures, 4 fractures of the tibia and fibula, one fracture of the medial malleolus, one of the lateral malleolus and one bimalleolar fracture. Hence an X-ray of the leg should always be taken. Twenty-six patients were treated on the ward, 77 as outpatients. The mean total time of healing in the group as a whole was 25 days and 44 days in patients having a fracture. Heel avulsion injuries caused by the spokes need special attention. The vitality of the crushed and dirty, caudally or medially based skin flap is minimal and very often yields a marginal or total necrosis if primary suture is done.", "contents": "Bicycle and moped spoke injuries in children. Analysis of 103 consecutive cases. The series consists of 60 boys and 43 girls, aged from 1 to 14 years, mean 4.95 years, whose right (42) or left (61) foot was caught between the bicycle (97) or moped (6) spokes. The skin was involved with ankle sprain, with fracture or without other injuries in 97 children; lateral aspect of the ankle and foot in 65 and heel in 21 patients. The X-rays revealed 10 tibial fractures, 4 fractures of the tibia and fibula, one fracture of the medial malleolus, one of the lateral malleolus and one bimalleolar fracture. Hence an X-ray of the leg should always be taken. Twenty-six patients were treated on the ward, 77 as outpatients. The mean total time of healing in the group as a whole was 25 days and 44 days in patients having a fracture. Heel avulsion injuries caused by the spokes need special attention. The vitality of the crushed and dirty, caudally or medially based skin flap is minimal and very often yields a marginal or total necrosis if primary suture is done."}
{"id": "PMID:237467", "title": "[Extraction of rifamycin B from native and aqueous solutions].", "content": "Optimal conditions for extraction of rifamycin B from aqueous solutions and fermentation broth filtrates at pH values within 2.0-7.0 were determined. When the antibiotic was extracted from the aqueous solutions, the highest yield was obtained at pH 2.0. When the antibiotic was extracted from the fermentation broth filtrates, it was found that chloroform was the most selective solvent with respect to rifamycin B, the chloroform selectivity being increased at pH 3.5-4.0. It was shown that rifamicin B passed from the buffer solutions with a concentration of 3-20 mg/ml to chloroform in amounts of 6-7 mg/ml and to ethylacetate and butanol in amounts of 20 mg/ml. Such conditions of chloroform and butanol (9 : 1) increased the rifamycin B contents in the extract up to 40 mg/ml.", "contents": "[Extraction of rifamycin B from native and aqueous solutions]. Optimal conditions for extraction of rifamycin B from aqueous solutions and fermentation broth filtrates at pH values within 2.0-7.0 were determined. When the antibiotic was extracted from the aqueous solutions, the highest yield was obtained at pH 2.0. When the antibiotic was extracted from the fermentation broth filtrates, it was found that chloroform was the most selective solvent with respect to rifamycin B, the chloroform selectivity being increased at pH 3.5-4.0. It was shown that rifamicin B passed from the buffer solutions with a concentration of 3-20 mg/ml to chloroform in amounts of 6-7 mg/ml and to ethylacetate and butanol in amounts of 20 mg/ml. Such conditions of chloroform and butanol (9 : 1) increased the rifamycin B contents in the extract up to 40 mg/ml."}
{"id": "PMID:237468", "title": "[Action of migillin on its own producer, Asp. fumigatus].", "content": "Addition of migillin to the nutrient medium at early stages of the fungus development induced at one hand inhibition of the fungus growth during the first 24-48 hours and stimulation of the biomass accumulation during the following hours of the development and on the other hand it induced inactivation of migillin added and inhibition of production of the \"own\" antibiotic. The migillin effect was accompanied by a delay in liberation of the substance with adsorption at 260nm from the mycelium.", "contents": "[Action of migillin on its own producer, Asp. fumigatus]. Addition of migillin to the nutrient medium at early stages of the fungus development induced at one hand inhibition of the fungus growth during the first 24-48 hours and stimulation of the biomass accumulation during the following hours of the development and on the other hand it induced inactivation of migillin added and inhibition of production of the \"own\" antibiotic. The migillin effect was accompanied by a delay in liberation of the substance with adsorption at 260nm from the mycelium."}
{"id": "PMID:237470", "title": "Activity of pure streptovaricins and fractionated streptovaricin complex against Friend virus.", "content": "Chromatographic fractionation of streptovaricin complex yields two stable components enriched (4- to 16-fold) in activity directed against the polycythemic strain of Friend virus; both components apparently contain no streptovaricins. When compared with their unfractionated parent streptovaricin complex, eight individual intact streptovaricins (A through G and J) show at least a 30-fold reduction in antiviral activity. These results further support the conclusion that the diversified biological properties of streptovaricin complex probably reside in different molecular structures.", "contents": "Activity of pure streptovaricins and fractionated streptovaricin complex against Friend virus. Chromatographic fractionation of streptovaricin complex yields two stable components enriched (4- to 16-fold) in activity directed against the polycythemic strain of Friend virus; both components apparently contain no streptovaricins. When compared with their unfractionated parent streptovaricin complex, eight individual intact streptovaricins (A through G and J) show at least a 30-fold reduction in antiviral activity. These results further support the conclusion that the diversified biological properties of streptovaricin complex probably reside in different molecular structures."}
{"id": "PMID:237490", "title": "Management of chemical cyanosis by oxygen saturation readings.", "content": "Chemical cyanosis is an oxygen transport deficiency produced by exposure to aromatic nitro- or animo-compounds. Evaluation of its severity by methemoglobin determinations defines the problem incompletely and is time consuming. Twenty-nine patients were studied over a five-year period by both methemoglobin level using classical laboratory methods and oxygen saturation level, using a reflection oximeter. The two results were found to bear an inverse linear relationship. Oxygen saturation may be determined easily and rapidly by the reflection oximeter method, and may be used safely as a guide to treatment of chemical cyanosis. No changes would have been made in medical management of any of the patients if the decisions had been made on the basis of the oxygen saturation level of less than 90% rather than the methemoglobin percentage of 10% or more.", "contents": "Management of chemical cyanosis by oxygen saturation readings. Chemical cyanosis is an oxygen transport deficiency produced by exposure to aromatic nitro- or animo-compounds. Evaluation of its severity by methemoglobin determinations defines the problem incompletely and is time consuming. Twenty-nine patients were studied over a five-year period by both methemoglobin level using classical laboratory methods and oxygen saturation level, using a reflection oximeter. The two results were found to bear an inverse linear relationship. Oxygen saturation may be determined easily and rapidly by the reflection oximeter method, and may be used safely as a guide to treatment of chemical cyanosis. No changes would have been made in medical management of any of the patients if the decisions had been made on the basis of the oxygen saturation level of less than 90% rather than the methemoglobin percentage of 10% or more."}
{"id": "PMID:237492", "title": "Lymphocyte proliferation to artery antigen as a positive diagnostic test in polymyalgia rheumatica.", "content": "The transformation response of peripheral blood lymphocytes in vitro to human arterial and muscle antigen has been studied in patients with polymyalgia rheumatica, polymyositis, rheumatoid arthritis, and polyarteritis, and polyarteritis nodosa and in unrelated controls. Lymphocytes from patients with polymyalgia rheumatica showed transformation responses significantly higher to artery antigen than those in the other disease and control groups. The highest responses were found in patients with evidence of the most active clinical disease at the time of testing. It is suggested that the transformation response to arterial antigen might aid the diagnosis of polymyalgia rheumatica.", "contents": "Lymphocyte proliferation to artery antigen as a positive diagnostic test in polymyalgia rheumatica. The transformation response of peripheral blood lymphocytes in vitro to human arterial and muscle antigen has been studied in patients with polymyalgia rheumatica, polymyositis, rheumatoid arthritis, and polyarteritis, and polyarteritis nodosa and in unrelated controls. Lymphocytes from patients with polymyalgia rheumatica showed transformation responses significantly higher to artery antigen than those in the other disease and control groups. The highest responses were found in patients with evidence of the most active clinical disease at the time of testing. It is suggested that the transformation response to arterial antigen might aid the diagnosis of polymyalgia rheumatica."}
{"id": "PMID:237493", "title": "A double blind trial to assess the value of alclofenac compared with phenylbutazone in the management of rheumatoid arthritis.", "content": "A double-blind cross-over study using a double placebo technique was employed to compare the effectiveness of daily alclofenac 3 g and phenylbutazone 300 mg in rheumatoid arthritis. (2) Thirty-one patients with classical or definite rheumatoid arthritis entered the trial. Twenty-three patients completed the trial; eight patients were withdrawn while on alclofenac, six developing a rash and two having inadequate analgesia. (3) Relief of pain on both drugs was comparable. (4) When questioned at the end of the trial, sixteen patients preferred phenylbutazone, four preferred alclofenac. (5) No significant changes in laboratory values were found, apart from a slight mean fall in haemoglobin on phenylbutazone. (6) There were significantly more side effects on alclofenac and rashes were particularly prominent.", "contents": "A double blind trial to assess the value of alclofenac compared with phenylbutazone in the management of rheumatoid arthritis. A double-blind cross-over study using a double placebo technique was employed to compare the effectiveness of daily alclofenac 3 g and phenylbutazone 300 mg in rheumatoid arthritis. (2) Thirty-one patients with classical or definite rheumatoid arthritis entered the trial. Twenty-three patients completed the trial; eight patients were withdrawn while on alclofenac, six developing a rash and two having inadequate analgesia. (3) Relief of pain on both drugs was comparable. (4) When questioned at the end of the trial, sixteen patients preferred phenylbutazone, four preferred alclofenac. (5) No significant changes in laboratory values were found, apart from a slight mean fall in haemoglobin on phenylbutazone. (6) There were significantly more side effects on alclofenac and rashes were particularly prominent."}
{"id": "PMID:237494", "title": "Functional changes in platelets during extracorporeal circulation.", "content": "An in vitro trauma test was conducted to determine the effects of extracorporeal circulation on platelet count and function. Fresh human blood was circulated in two identical in vitro circuits for six hours at a rate of 500 ml per minute (500 recirculations). One circuit included a G.E.--Peirce membrane lung and the other was a control. Platelet aggregation induced by adenosine diphosphate (ADP), epinephrine, or collagen was studied before and after six hours of perfusion. No important drop in platelet count occurred in the control circuit (Control-C) following bypass, but there was a 20% drop for the lung circuit (Lung-C). Platelet aggregation was reduced by about 30% for the control circuit and 65% for the lung circuit. The large decrease in platelet function accompanied by only a moderate decrease in platelet count is discussed in terms of loss of the youngest and most active platelets, platelet inhibition due to ADP released by red blood cell lysis, and platelet trauma.", "contents": "Functional changes in platelets during extracorporeal circulation. An in vitro trauma test was conducted to determine the effects of extracorporeal circulation on platelet count and function. Fresh human blood was circulated in two identical in vitro circuits for six hours at a rate of 500 ml per minute (500 recirculations). One circuit included a G.E.--Peirce membrane lung and the other was a control. Platelet aggregation induced by adenosine diphosphate (ADP), epinephrine, or collagen was studied before and after six hours of perfusion. No important drop in platelet count occurred in the control circuit (Control-C) following bypass, but there was a 20% drop for the lung circuit (Lung-C). Platelet aggregation was reduced by about 30% for the control circuit and 65% for the lung circuit. The large decrease in platelet function accompanied by only a moderate decrease in platelet count is discussed in terms of loss of the youngest and most active platelets, platelet inhibition due to ADP released by red blood cell lysis, and platelet trauma."}
{"id": "PMID:237495", "title": "Continuous percutaneous monitoring of muscle pH and oxygen pressure. A new technique for in vivo use.", "content": "Newly developed all solid state catheter oxygen pressure (PO2)  and pH electrodes were evaluated in dogs in respiratory acidosis and hemorrhagic shock. The electrodes were inserted into the blood vessels and thigh muscle by a percutaneous puncture technique. In animals with respiratory acidosis, arterial, venous, and intramuscular pH decreased in parallel as arterial carbon dioxide pressure (PCO2) increased. During severe acidosis, arterial and venous PO2 did not change appreciably, but intramuscular PO2 decreased moderately, indicating decreased tissue perfusion. In animals with hemorrhagic shock, intramuscular PO2 decreased in proportion to the blood loss, whereas the reduction in intramuscular pH and blood pressure lagged behind blood loss. A similar finding was observed during reinfusion of shed blood in surviving animals. In the animals that died, intramuscular PO2 AND PH remained low after the reinfusion of all shed blood, although arterial blood pressure did return to base line levels.", "contents": "Continuous percutaneous monitoring of muscle pH and oxygen pressure. A new technique for in vivo use. Newly developed all solid state catheter oxygen pressure (PO2)  and pH electrodes were evaluated in dogs in respiratory acidosis and hemorrhagic shock. The electrodes were inserted into the blood vessels and thigh muscle by a percutaneous puncture technique. In animals with respiratory acidosis, arterial, venous, and intramuscular pH decreased in parallel as arterial carbon dioxide pressure (PCO2) increased. During severe acidosis, arterial and venous PO2 did not change appreciably, but intramuscular PO2 decreased moderately, indicating decreased tissue perfusion. In animals with hemorrhagic shock, intramuscular PO2 decreased in proportion to the blood loss, whereas the reduction in intramuscular pH and blood pressure lagged behind blood loss. A similar finding was observed during reinfusion of shed blood in surviving animals. In the animals that died, intramuscular PO2 AND PH remained low after the reinfusion of all shed blood, although arterial blood pressure did return to base line levels."}
{"id": "PMID:237496", "title": "Hydrochloric acid in the correction of metabolic alkalosis.", "content": "Intravenous infusion of hydrochloric acid was used as a safe, effective, and quantitative method for correction of metabolic alkalosis in two patients. The first shows the risks of intravenously administered ammonium chloride, the currently available alternative to hydrochloric acid therapy. The second shows the efficacy of intravenously administered hydrochloric acid. While breathing spontaneously throughout the period of severe alkalosis, this patient showed compensatory hypoventilation with conspicuous increase in arterial carbon dioxide pressure. Normal spontaneous ventilation returned with correction of the metabolic alkalosis.", "contents": "Hydrochloric acid in the correction of metabolic alkalosis. Intravenous infusion of hydrochloric acid was used as a safe, effective, and quantitative method for correction of metabolic alkalosis in two patients. The first shows the risks of intravenously administered ammonium chloride, the currently available alternative to hydrochloric acid therapy. The second shows the efficacy of intravenously administered hydrochloric acid. While breathing spontaneously throughout the period of severe alkalosis, this patient showed compensatory hypoventilation with conspicuous increase in arterial carbon dioxide pressure. Normal spontaneous ventilation returned with correction of the metabolic alkalosis."}
{"id": "PMID:237497", "title": "Inactivation of African horse-sickness virus by betapropiolactone and by pH.", "content": "The inactivation of several types of African horse sickness virus (AHSV) by pH and by betapropiolactone (BPL) was studied. At 19 degrees - 22 degrees C the virus was stable between pH 6.0 and 10.4, whether suspended in mouse brain or in serumfree buffer. Below pH 5.6 and above pH 10.9, more than 99 per cent of infectivity was inactivated within 15 minutes. The addition of 50 per cent serum did not influence pH stability. Disinfection in the presence of citric acid and caustic soda is briefly discussed. Inactivation by BPL was complete within 30 minutes at 37 degrees C, yet incomplete after 15 hours at 4 degrees C. Types 3 and 9 virus grown in suckling mouse brain and types 1, 3 and 9 produced in pig kidney cells were equally susceptible to 0.1 per cent BPL, more than 99.9 per cent being inactivated. The effectiveness of BPL was reduced at least 10-fold by the addition of 50 per cent serum. No infective virus was detected following incubation of either tissue culture virus with 0.2 per cent BPL or of mouse brain virus with 0.3 per cent BPL. Virus suspensions exposed to 0.3 per cent BPL required buffering with Tris of at least 0.05 molar strength in order to maintain the pH within an acceptable range. Inactivated antigens prepared with 0.4 per cent or lower concentrations of BPL were immunogenic in guinea pigs.", "contents": "Inactivation of African horse-sickness virus by betapropiolactone and by pH. The inactivation of several types of African horse sickness virus (AHSV) by pH and by betapropiolactone (BPL) was studied. At 19 degrees - 22 degrees C the virus was stable between pH 6.0 and 10.4, whether suspended in mouse brain or in serumfree buffer. Below pH 5.6 and above pH 10.9, more than 99 per cent of infectivity was inactivated within 15 minutes. The addition of 50 per cent serum did not influence pH stability. Disinfection in the presence of citric acid and caustic soda is briefly discussed. Inactivation by BPL was complete within 30 minutes at 37 degrees C, yet incomplete after 15 hours at 4 degrees C. Types 3 and 9 virus grown in suckling mouse brain and types 1, 3 and 9 produced in pig kidney cells were equally susceptible to 0.1 per cent BPL, more than 99.9 per cent being inactivated. The effectiveness of BPL was reduced at least 10-fold by the addition of 50 per cent serum. No infective virus was detected following incubation of either tissue culture virus with 0.2 per cent BPL or of mouse brain virus with 0.3 per cent BPL. Virus suspensions exposed to 0.3 per cent BPL required buffering with Tris of at least 0.05 molar strength in order to maintain the pH within an acceptable range. Inactivated antigens prepared with 0.4 per cent or lower concentrations of BPL were immunogenic in guinea pigs."}
{"id": "PMID:237498", "title": "A primate model for testing anticonvulsant drugs.", "content": "Senegalese baboons (Papio papio), with a natural syndrome of photosensitive epilepsy, consistently show generalized myoclonic jerks if stimulated stroboscopically at hourly intervals, two to eight hours after the intravenous administration of allylglycine, 200 mg/kg. This provides a model for testing the acute antiepileptic effects of established or new drugs. The relationship between concentration of drug, antiepileptic action, and acute neurological toxic effects can be studied. Pnehobarbital (15 mg/kg) and diazepam (0;5 to 1.5 mg/kg) were highly effective in the absence of signs of toxic reaction (plasma levels: phenobarbital sodium, 0.7 to 1.7 mg/100 ml; diazepam, greater than 0.5 mug/ml). After administration of carbamazepine (30 to 40 mg/kg) and diphenylhydantoin sodium (40 to 50 mg/kg), antiepileptic action was seen, but was accompanied by severe toxic signs (nystagmus and ataxia). Sulthiame (20 to 125 mg/kg) and ethosuximide (50 to 100 mg/kg) had little antiepileptic activity and no acute toxic effects. This primate model may aid the identification of new drugs that are active against grand mal seizures and status epilepticus.", "contents": "A primate model for testing anticonvulsant drugs. Senegalese baboons (Papio papio), with a natural syndrome of photosensitive epilepsy, consistently show generalized myoclonic jerks if stimulated stroboscopically at hourly intervals, two to eight hours after the intravenous administration of allylglycine, 200 mg/kg. This provides a model for testing the acute antiepileptic effects of established or new drugs. The relationship between concentration of drug, antiepileptic action, and acute neurological toxic effects can be studied. Pnehobarbital (15 mg/kg) and diazepam (0;5 to 1.5 mg/kg) were highly effective in the absence of signs of toxic reaction (plasma levels: phenobarbital sodium, 0.7 to 1.7 mg/100 ml; diazepam, greater than 0.5 mug/ml). After administration of carbamazepine (30 to 40 mg/kg) and diphenylhydantoin sodium (40 to 50 mg/kg), antiepileptic action was seen, but was accompanied by severe toxic signs (nystagmus and ataxia). Sulthiame (20 to 125 mg/kg) and ethosuximide (50 to 100 mg/kg) had little antiepileptic activity and no acute toxic effects. This primate model may aid the identification of new drugs that are active against grand mal seizures and status epilepticus."}
{"id": "PMID:237499", "title": "Plasma albumin concentration and diphenylhydantoin binding in man.", "content": "The plasma protein binding of diphenylhydantoin sodium was determined in 26 patients who had been taking diphenylhydantoin regularly for more than two weeks. The free (unbound) diphenylhydantoin level was found to vary from 5.8% to 12.6% of the total drug concentration. This range of variation may be clinically important, if it can be established that the binding of diphenylhydantoin to plasma proteins limits entry of the drug into the brain. The binding of diphenylhydantoin was directly proportional to the plasma albumin concentration, which thus appeared to be the most important determinant of diphenylhydantoin binding. Diphenylhydantoin binding was independent of the plasma concentration of the drug in the usual therapeutic range. In vitro studies showed little effect by phenobarbital sodium or penicillin G; therapeutic levels of acetylsalicylic acid, however, increased free diphenylhydantoin by nearly 50%.", "contents": "Plasma albumin concentration and diphenylhydantoin binding in man. The plasma protein binding of diphenylhydantoin sodium was determined in 26 patients who had been taking diphenylhydantoin regularly for more than two weeks. The free (unbound) diphenylhydantoin level was found to vary from 5.8% to 12.6% of the total drug concentration. This range of variation may be clinically important, if it can be established that the binding of diphenylhydantoin to plasma proteins limits entry of the drug into the brain. The binding of diphenylhydantoin was directly proportional to the plasma albumin concentration, which thus appeared to be the most important determinant of diphenylhydantoin binding. Diphenylhydantoin binding was independent of the plasma concentration of the drug in the usual therapeutic range. In vitro studies showed little effect by phenobarbital sodium or penicillin G; therapeutic levels of acetylsalicylic acid, however, increased free diphenylhydantoin by nearly 50%."}
{"id": "PMID:237500", "title": "Ocular anti-inflammatory effect of fenoprofen. Dose-response study.", "content": "An experimental rabbit uveitis model was used to establish a dose response range for topical administration of fenoprofen (dl-2(3-phenoxyphenyl) propionic acid. The 0.3% concentrate group was not distinguishable from the untreated group, and 3% concentrate proved highly irritating. Fenoprofen 1%, pH 6.4, proved most efficacious and had an effect comparable to dexamethasone phosphate 0.1%, seen in a previous study.", "contents": "Ocular anti-inflammatory effect of fenoprofen. Dose-response study. An experimental rabbit uveitis model was used to establish a dose response range for topical administration of fenoprofen (dl-2(3-phenoxyphenyl) propionic acid. The 0.3% concentrate group was not distinguishable from the untreated group, and 3% concentrate proved highly irritating. Fenoprofen 1%, pH 6.4, proved most efficacious and had an effect comparable to dexamethasone phosphate 0.1%, seen in a previous study."}
{"id": "PMID:237503", "title": "Fibre in nutrition.", "content": "The physical properties and the chemical variety of the substances which make up the plant cell wall are inadequately described by any one term such as \"fibre\". It would seem that an understanding of the role of the unavailable carbohydrates and lignin in the diet in the functioning of the gastro-intestinal tract and on possible pathological process must be based on a better knowledge of the chemical and physical properties of these substances as they occur in foods than is at present available. It is suggested that this knowledge can come from a synthesis of the findings of the plant anatomists, plant biochemists and structural organic chemists and the application of this synthesis to studies in man.", "contents": "Fibre in nutrition. The physical properties and the chemical variety of the substances which make up the plant cell wall are inadequately described by any one term such as \"fibre\". It would seem that an understanding of the role of the unavailable carbohydrates and lignin in the diet in the functioning of the gastro-intestinal tract and on possible pathological process must be based on a better knowledge of the chemical and physical properties of these substances as they occur in foods than is at present available. It is suggested that this knowledge can come from a synthesis of the findings of the plant anatomists, plant biochemists and structural organic chemists and the application of this synthesis to studies in man."}
{"id": "PMID:237501", "title": "[Myocardial metabolism under intravenous infusion of glucagon (author's transl)].", "content": "In 7 healthy-hearted probands the arterial-coronary-venous oxygen difference for glucose, K+, lactate, pO2, pCO2 and pH during a glucagon infusion was determined and compared with the values before and 10 minutes after infusion. Contradictory to the unchanged myocardial lactate extraction and the positively or negatively influenced K+-uptake recorded in the literature, in this contingent there was a statistically significant myocardial lactate production and an unchanged potassium uptake. The respiratory quotient of the heart increased. These changes are regarded as the result of a direct hormonal influence on the myocardial metabolism and have nothing to do with the change of an aerobic into an anaerobic metabolic state.", "contents": "[Myocardial metabolism under intravenous infusion of glucagon (author's transl)]. In 7 healthy-hearted probands the arterial-coronary-venous oxygen difference for glucose, K+, lactate, pO2, pCO2 and pH during a glucagon infusion was determined and compared with the values before and 10 minutes after infusion. Contradictory to the unchanged myocardial lactate extraction and the positively or negatively influenced K+-uptake recorded in the literature, in this contingent there was a statistically significant myocardial lactate production and an unchanged potassium uptake. The respiratory quotient of the heart increased. These changes are regarded as the result of a direct hormonal influence on the myocardial metabolism and have nothing to do with the change of an aerobic into an anaerobic metabolic state."}
{"id": "PMID:237505", "title": "Carbamyl phosphate synthesis in Bacillus subtilis.", "content": "In vitro and \"in situ\" assays have been developed to test the carbamyl phosphate synthetase (CPSase) activity of a series of pyrimidine-requiring mutants of Bacillus subtilis. The enzyme has been shown to be highly unstable, and was successfully extracted only in the presence of 10% glycerol and 1 mM dithiothreitol (Cleland's reagent). It loses activity rapidly when sonicated or when treated with lysozyme. Genetic studies, using mutants, indicate that B. subtilis may possess two CPSases. This possibility and its physiological consequences were probed enzymatically. CPSase activity has been shown to undergo inhibition by both uridine triphosphate and dihydroorotate; activation has been demonstrated in response to phosphoribosyl pyrophosphate (PRPP) and (to a lesser extent) ornithine.", "contents": "Carbamyl phosphate synthesis in Bacillus subtilis. In vitro and \"in situ\" assays have been developed to test the carbamyl phosphate synthetase (CPSase) activity of a series of pyrimidine-requiring mutants of Bacillus subtilis. The enzyme has been shown to be highly unstable, and was successfully extracted only in the presence of 10% glycerol and 1 mM dithiothreitol (Cleland's reagent). It loses activity rapidly when sonicated or when treated with lysozyme. Genetic studies, using mutants, indicate that B. subtilis may possess two CPSases. This possibility and its physiological consequences were probed enzymatically. CPSase activity has been shown to undergo inhibition by both uridine triphosphate and dihydroorotate; activation has been demonstrated in response to phosphoribosyl pyrophosphate (PRPP) and (to a lesser extent) ornithine."}
{"id": "PMID:237515", "title": "The effect of carbon dioxide on the neuromuscular and haemodunamic effects of AH 8265, a new non-depolarizing muscle relaxant.", "content": "The influence of carbon dioxide on the neuromuscular and haemodynamic effects of AH 8165, a new non-depolarizing muscle relaxant, was determined in nine healthy patients before the onset of minor elective surgery. Five patients (hypocapnic, group I) were maintained at an arterial Pco2 ranging from 25 to 31  mm Hg; four patients (hypercapnic, group II) at a Cco2 from 54 to 57 mm Hg. AH 8165 0.25 MG/KG (one-quarter of the dose required for intubation) was given by rapid central venous injection. Haemodynamic responses were similar in the two groups; there were increases in heart rate ranging from 45 to 60 per cent, increases in mean arterial pressure of 17 - 20 percent, and increases in cardiac output of 22-32 per cent. The intensity of neuromuscular blockade of the forearm muscles after AH 8165 was similar in the two groups, and there was no significant difference in recovery rates; group I patients were 80 percent recovered in 36.6 min. group II patients in 47.3 min. It was concluded that the activity of AH 8165 was not influenced by moderate changes in respiratory acid base status.", "contents": "The effect of carbon dioxide on the neuromuscular and haemodunamic effects of AH 8265, a new non-depolarizing muscle relaxant. The influence of carbon dioxide on the neuromuscular and haemodynamic effects of AH 8165, a new non-depolarizing muscle relaxant, was determined in nine healthy patients before the onset of minor elective surgery. Five patients (hypocapnic, group I) were maintained at an arterial Pco2 ranging from 25 to 31  mm Hg; four patients (hypercapnic, group II) at a Cco2 from 54 to 57 mm Hg. AH 8165 0.25 MG/KG (one-quarter of the dose required for intubation) was given by rapid central venous injection. Haemodynamic responses were similar in the two groups; there were increases in heart rate ranging from 45 to 60 per cent, increases in mean arterial pressure of 17 - 20 percent, and increases in cardiac output of 22-32 per cent. The intensity of neuromuscular blockade of the forearm muscles after AH 8165 was similar in the two groups, and there was no significant difference in recovery rates; group I patients were 80 percent recovered in 36.6 min. group II patients in 47.3 min. It was concluded that the activity of AH 8165 was not influenced by moderate changes in respiratory acid base status."}
{"id": "PMID:237516", "title": "Maternal arterial oxygen tension during intermittent inhalation analgesia.", "content": "In mothers nursed in a semi-recumbent position, arterial oxygen tension was measured at the beginning and END OF AN an intermittent period of inhalation, Lasting for six contractions, during the first stage of labour. Ten mothers had methoxyflurane 0.35 per cent and air, followed by methoxyflurane 0.35 per cent with approximately 50 per cent oxygen. Another 10 mothers had 50 per cent nitrous oxide and 50 per cent oxygen (Entonox). The mean values of PaO2 at the beginning of periods of inhalation in those who received methoxyflurane in air, methoxyflurane in 50 per cent oxygen, and nitrous oxide in oxygen were 109, 120 and 106 mm Hg respectively. The mean increases in PaO2 by the ends of periods of inhalation were 18, 43 and 63 mm Hg respectively. On average, increasing the inspired concentration of oxygen to 50 per cent significantly and substantially increased maternal PsO2 with both agents by the emd pf inhalation. There would therefore be some increase in available oxygen during the phase of higher blood flow following a uterine contraction. However, the lowest maternal PaO2 measured was 72 mm Hg; therefore additional oxygen is unlikely to offer much advantage except in patients with respiratory or cardiac deficiencies. In the intervals between inhalations of the analgesic mixture the PaO2 decreased to about the level found during air breathing. Consequently it would be necessary to breather additional oxygen continuously, between as well as during contractions, to ensure an increased maternal PaO2 throughout labour.", "contents": "Maternal arterial oxygen tension during intermittent inhalation analgesia. In mothers nursed in a semi-recumbent position, arterial oxygen tension was measured at the beginning and END OF AN an intermittent period of inhalation, Lasting for six contractions, during the first stage of labour. Ten mothers had methoxyflurane 0.35 per cent and air, followed by methoxyflurane 0.35 per cent with approximately 50 per cent oxygen. Another 10 mothers had 50 per cent nitrous oxide and 50 per cent oxygen (Entonox). The mean values of PaO2 at the beginning of periods of inhalation in those who received methoxyflurane in air, methoxyflurane in 50 per cent oxygen, and nitrous oxide in oxygen were 109, 120 and 106 mm Hg respectively. The mean increases in PaO2 by the ends of periods of inhalation were 18, 43 and 63 mm Hg respectively. On average, increasing the inspired concentration of oxygen to 50 per cent significantly and substantially increased maternal PsO2 with both agents by the emd pf inhalation. There would therefore be some increase in available oxygen during the phase of higher blood flow following a uterine contraction. However, the lowest maternal PaO2 measured was 72 mm Hg; therefore additional oxygen is unlikely to offer much advantage except in patients with respiratory or cardiac deficiencies. In the intervals between inhalations of the analgesic mixture the PaO2 decreased to about the level found during air breathing. Consequently it would be necessary to breather additional oxygen continuously, between as well as during contractions, to ensure an increased maternal PaO2 throughout labour."}
{"id": "PMID:237517", "title": "The use of a small endotracheal tube in bronchoscopy.", "content": "The use of the standard 4-mm cuffed endotracheal tube to deliver manually or mechanically interrupted jets of oxygen or nitrous oxide and oxygen into the trachea allowed bronchoscopy and other related procedures to be performed with advantage to the patient, the surgeon and the anawsthetist. This paper describes the equipment used and the advantages obtained.", "contents": "The use of a small endotracheal tube in bronchoscopy. The use of the standard 4-mm cuffed endotracheal tube to deliver manually or mechanically interrupted jets of oxygen or nitrous oxide and oxygen into the trachea allowed bronchoscopy and other related procedures to be performed with advantage to the patient, the surgeon and the anawsthetist. This paper describes the equipment used and the advantages obtained."}
{"id": "PMID:237514", "title": "[Parenteral nutrition in critically ill newborns].", "content": "In nine critically ill newborns, five of them with intractable diarrhea and four surgical patients, we administered a 5% crystalline aminoacids solution (AA) and glucose in sufficient amount to provide 120 cal times kg. in 24 hours. Six of them recovered after receiving parenteral alimentation for 3 to 15 days, gained weight during or after treatment and were discharged from the hospital in good conditions. Three died, one of them presented septicemia and two pneumonia and pulmonary infarcts. The solution used generated few metabolic alterations, the acid-base status remained within normal range and there were not important changes in the sodium and potassium serum concentrations. On the contrary, children with hyponatremia and hypokalemia at the beginning of the treatment, normalized these constants within the first hours, as diarrhea ceased. The most frequent complications were infiltrations and reaction of the surrounding tissue of the catheterized vein and local skin infection. Only one patient died of septicemia, possibly caused by this proceeding. In summary, parenteral alimentation though not free from risk, seems to be a useful proceeding when oral feeding is impossible or inadvisable. The utmost danger is septicemia. Metabolic changes are minimal and they do not mean a risk for child's life; nevertheless, there is a need for long term studies to bring up definite conclusions. The solutions in actual use are probably not the most physiological for the newborn. It is necessary to adequate them according to the new advances made on child nourishment during his first days of life.", "contents": "[Parenteral nutrition in critically ill newborns]. In nine critically ill newborns, five of them with intractable diarrhea and four surgical patients, we administered a 5% crystalline aminoacids solution (AA) and glucose in sufficient amount to provide 120 cal times kg. in 24 hours. Six of them recovered after receiving parenteral alimentation for 3 to 15 days, gained weight during or after treatment and were discharged from the hospital in good conditions. Three died, one of them presented septicemia and two pneumonia and pulmonary infarcts. The solution used generated few metabolic alterations, the acid-base status remained within normal range and there were not important changes in the sodium and potassium serum concentrations. On the contrary, children with hyponatremia and hypokalemia at the beginning of the treatment, normalized these constants within the first hours, as diarrhea ceased. The most frequent complications were infiltrations and reaction of the surrounding tissue of the catheterized vein and local skin infection. Only one patient died of septicemia, possibly caused by this proceeding. In summary, parenteral alimentation though not free from risk, seems to be a useful proceeding when oral feeding is impossible or inadvisable. The utmost danger is septicemia. Metabolic changes are minimal and they do not mean a risk for child's life; nevertheless, there is a need for long term studies to bring up definite conclusions. The solutions in actual use are probably not the most physiological for the newborn. It is necessary to adequate them according to the new advances made on child nourishment during his first days of life."}
{"id": "PMID:237518", "title": "The effect of seven vasopressors of halothane MAC in dogs.", "content": "We evaluated the effects of ephedrine, mephentermine, metaraminol, phenylephrine, methoxamine, noradrenaline and adrenaline on halothane anaesthetic requirement (MAC) in dogs. MAC increased significantly only during ephedrine infusion (50%) although significance was approached with mephentermine (21%). Phenylephrine, metaraminol, methoxamine, noradrenaline and adrenaline did not change MAC. Arterial pressure was increased 50-100% with all agents. Our results support the hypothesis that anaesthetic requirement may be related, in part, to release of brain noradrenaline.", "contents": "The effect of seven vasopressors of halothane MAC in dogs. We evaluated the effects of ephedrine, mephentermine, metaraminol, phenylephrine, methoxamine, noradrenaline and adrenaline on halothane anaesthetic requirement (MAC) in dogs. MAC increased significantly only during ephedrine infusion (50%) although significance was approached with mephentermine (21%). Phenylephrine, metaraminol, methoxamine, noradrenaline and adrenaline did not change MAC. Arterial pressure was increased 50-100% with all agents. Our results support the hypothesis that anaesthetic requirement may be related, in part, to release of brain noradrenaline."}
{"id": "PMID:237519", "title": "Studies of drugs given before anaesthesia XXV: Medazepam, a new benzodiazepine.", "content": "Medazepam, a new benzodiazepine, was studied as an oral preanaesthetic medication in adult women in a dose of 10 mg, and the findings compared with those obtained with diazepam 10 mg or a dummy capsule using a double-blind technique. In the doses used medazepam produced less drowsiness than diazepam and was no more anxiolytic than the placebo.", "contents": "Studies of drugs given before anaesthesia XXV: Medazepam, a new benzodiazepine. Medazepam, a new benzodiazepine, was studied as an oral preanaesthetic medication in adult women in a dose of 10 mg, and the findings compared with those obtained with diazepam 10 mg or a dummy capsule using a double-blind technique. In the doses used medazepam produced less drowsiness than diazepam and was no more anxiolytic than the placebo."}
{"id": "PMID:237520", "title": "A simple method for computing acid-base state.", "content": "Simple methods are described for computing the variables derived from the Siggaard-Andersen nomogram, where the in vitro buffer line is either established by direct measurement or calculated from measurements of pH, Pco2 and haemoglobin. Calculations are performed using the equation of the pH-log Pco2 buffer line, the Henderson-Hasselbalch equation, and the polynomials: BE=-38.402+1.8970 (SB)-0.013342 (SB)-2 m-equiv/litre; SL=-69.046+17.377 (pH40)-1.1121 (pH40)-2; SH=-123.30+31.357 (pH40)-2.0143 (pH40)-2. Then haemoglobin=7.5 (1+(S-SL)/(SH-SL)) G/100 ml, where S is the slope of the buffer line. Results are sufficiently accurate for clinical purposes.", "contents": "A simple method for computing acid-base state. Simple methods are described for computing the variables derived from the Siggaard-Andersen nomogram, where the in vitro buffer line is either established by direct measurement or calculated from measurements of pH, Pco2 and haemoglobin. Calculations are performed using the equation of the pH-log Pco2 buffer line, the Henderson-Hasselbalch equation, and the polynomials: BE=-38.402+1.8970 (SB)-0.013342 (SB)-2 m-equiv/litre; SL=-69.046+17.377 (pH40)-1.1121 (pH40)-2; SH=-123.30+31.357 (pH40)-2.0143 (pH40)-2. Then haemoglobin=7.5 (1+(S-SL)/(SH-SL)) G/100 ml, where S is the slope of the buffer line. Results are sufficiently accurate for clinical purposes."}
{"id": "PMID:237521", "title": "The effect of non-depolarizing relaxants on plasma potassium.", "content": "Plasma potassium concentrations were measured in four groups of unpremedicated patients in whom anesthesia was induced with thiopentone 5 mg/kg followed by tubocurarine 0.5 mg/kg, gallamine 2 mg/kg, pancuronium 0.1 mg/kg or AH 8165 1.25 mg/kg, prior to elective dental surgery. There was a small but consistent decrease in plasma potassium following the injection of pancuronium and, to a lesser extent, following gallamine. No changes were found during the first 10 min following tubocurrarine. With AH 8165 there was an early reduction in plasma potassium but the values returned to within normal limits by 5 min.", "contents": "The effect of non-depolarizing relaxants on plasma potassium. Plasma potassium concentrations were measured in four groups of unpremedicated patients in whom anesthesia was induced with thiopentone 5 mg/kg followed by tubocurarine 0.5 mg/kg, gallamine 2 mg/kg, pancuronium 0.1 mg/kg or AH 8165 1.25 mg/kg, prior to elective dental surgery. There was a small but consistent decrease in plasma potassium following the injection of pancuronium and, to a lesser extent, following gallamine. No changes were found during the first 10 min following tubocurrarine. With AH 8165 there was an early reduction in plasma potassium but the values returned to within normal limits by 5 min."}
{"id": "PMID:237522", "title": "Acid pulmonary aspiration syndrome after antacids. A case report.", "content": "This is a report of a patient who developed acid pulmonary aspiration syndrome following pulmonary aspiration of gastric contents at a pH of 3.5. The volume of the stomach contents was large and 15 ml of magnesium trisilicate was insufficient to prevent the effects of acid aspiration. After operation, considerable pulmonary shunting was demonstrable for several days. The patient was discharged home well, and a chest x-ray 2 months later showed no abnormality.", "contents": "Acid pulmonary aspiration syndrome after antacids. A case report. This is a report of a patient who developed acid pulmonary aspiration syndrome following pulmonary aspiration of gastric contents at a pH of 3.5. The volume of the stomach contents was large and 15 ml of magnesium trisilicate was insufficient to prevent the effects of acid aspiration. After operation, considerable pulmonary shunting was demonstrable for several days. The patient was discharged home well, and a chest x-ray 2 months later showed no abnormality."}
{"id": "PMID:237523", "title": "Pulmonary complications following smoke inhalation.", "content": "Two patients with severe respiratory disturbance following burning accidents are described. It is suggested that smoke inhalation injuries may in future present a more frequent problem in the intensive therapy unit, and the mechanisms of the disorder and its treatment are discussed.", "contents": "Pulmonary complications following smoke inhalation. Two patients with severe respiratory disturbance following burning accidents are described. It is suggested that smoke inhalation injuries may in future present a more frequent problem in the intensive therapy unit, and the mechanisms of the disorder and its treatment are discussed."}
{"id": "PMID:237526", "title": "Exercise-induced asthma.", "content": "A review of exercise-induced asthma is presented which describes work that has been carried out by the authors and by other investigators over recent years. The effect of exericse on lung function in asthmatic and normal subjects is compared. The influence of the type and severity of exercise on the response of the asthmatic is noted and the importance this has for interpretation of results. The effects of various drugs on exercise-induced asthma are considered in some detail. The clinical implications of the results of exercise tests in asthmatics, their relatives, and other subjects are considered in terms of the diagnosis and prognosis of asthma and its mode of inheritance. It is concluded that there is as yet no explantation for the mechanism of exercise-induced asthma, but it is a tool of potentially great value for research into the physiology and treatment of clinical asthma.", "contents": "Exercise-induced asthma. A review of exercise-induced asthma is presented which describes work that has been carried out by the authors and by other investigators over recent years. The effect of exericse on lung function in asthmatic and normal subjects is compared. The influence of the type and severity of exercise on the response of the asthmatic is noted and the importance this has for interpretation of results. The effects of various drugs on exercise-induced asthma are considered in some detail. The clinical implications of the results of exercise tests in asthmatics, their relatives, and other subjects are considered in terms of the diagnosis and prognosis of asthma and its mode of inheritance. It is concluded that there is as yet no explantation for the mechanism of exercise-induced asthma, but it is a tool of potentially great value for research into the physiology and treatment of clinical asthma."}
{"id": "PMID:237527", "title": "The physiological assessment of acid-base balance.", "content": "Acid-base terminology including the sue of SI units is reviewed. The historical reasons why nomograms have been particularly used in acid-base work are discussed. The theoretical basis of the Henderson-Hasselbalch equation is considered. It is emphasized that the solubility of CO2 in plasma and the apparent first dissociation constant of carbonic acid are not chemical constants when applied to media of uncertain and varying composition such as blood plasma. The use of the Henderson-Hasselbalch equation in making hypothermia corrections for PCO2 is discussed. The Astrup system for the in vitro determination of blood gases and derived parameters is described and the theoretical weakness of the base excess concept stressed. A more clinically-oriented approach to the assessment of acid-base problems is presented. Measurement of blood [H+] and PCO2 are considered to be primary data which should be recorded on a chart with in vivo CO2-titration lines (see below). Clinical information and results of other laboratory investigations such as plasma bicarbonate, PO2,P50 are then to be considered together with the primary data. In order to interpret this combined information it is essential to take into account the known ventilatory response to metabolic acidosis and alkalosis, and the renal response to respiratory acidosis and alkalosis. The use is recommended of a chart showing the whole-body CO2-titration points obtained when patients with different initial levels of non-respiratory [H+] are ventilated. A number of examples are given of the use of this [H+] and PCO2 in vivo chart in the interpretation of acid-base data. The aetiology, prognosis and treatment of metabolic alkalosis is briefly reviewed. Treatment with intravenous acid is recommended for established cases. Attention is drawn to the possibility of iatrogenic production of metabolic alkalosis. Caution is expressed over the use of intravenous alkali in all but the severest cases of metabolic acidosis. The role of 2,3-diphosphoglycerate on tissue oxygenation is stressed and use of intravenous sodium phosphate as an alternative to intravenous bicarbonate is mentioned.", "contents": "The physiological assessment of acid-base balance. Acid-base terminology including the sue of SI units is reviewed. The historical reasons why nomograms have been particularly used in acid-base work are discussed. The theoretical basis of the Henderson-Hasselbalch equation is considered. It is emphasized that the solubility of CO2 in plasma and the apparent first dissociation constant of carbonic acid are not chemical constants when applied to media of uncertain and varying composition such as blood plasma. The use of the Henderson-Hasselbalch equation in making hypothermia corrections for PCO2 is discussed. The Astrup system for the in vitro determination of blood gases and derived parameters is described and the theoretical weakness of the base excess concept stressed. A more clinically-oriented approach to the assessment of acid-base problems is presented. Measurement of blood [H+] and PCO2 are considered to be primary data which should be recorded on a chart with in vivo CO2-titration lines (see below). Clinical information and results of other laboratory investigations such as plasma bicarbonate, PO2,P50 are then to be considered together with the primary data. In order to interpret this combined information it is essential to take into account the known ventilatory response to metabolic acidosis and alkalosis, and the renal response to respiratory acidosis and alkalosis. The use is recommended of a chart showing the whole-body CO2-titration points obtained when patients with different initial levels of non-respiratory [H+] are ventilated. A number of examples are given of the use of this [H+] and PCO2 in vivo chart in the interpretation of acid-base data. The aetiology, prognosis and treatment of metabolic alkalosis is briefly reviewed. Treatment with intravenous acid is recommended for established cases. Attention is drawn to the possibility of iatrogenic production of metabolic alkalosis. Caution is expressed over the use of intravenous alkali in all but the severest cases of metabolic acidosis. The role of 2,3-diphosphoglycerate on tissue oxygenation is stressed and use of intravenous sodium phosphate as an alternative to intravenous bicarbonate is mentioned."}
{"id": "PMID:237528", "title": "The effect of intravenous ritodrine on the acid-base status of the fetus during the second stage of labour.", "content": "A progressive fetal respiratory acidosis occurs in the second stage of labour. A double-blind controlled trial showed that the intravenous infusion of Ritodrine abolished this.", "contents": "The effect of intravenous ritodrine on the acid-base status of the fetus during the second stage of labour. A progressive fetal respiratory acidosis occurs in the second stage of labour. A double-blind controlled trial showed that the intravenous infusion of Ritodrine abolished this."}
{"id": "PMID:237529", "title": "Indicator dyes as probes of electrostatic potential changes on macromolecular surfaces.", "content": "An indicator dye attached to an electrostatically charged macromolecular surface generally has a pK value (pKb') different from that of uncombined dye (pKf'). The question if changes in (pKb' - pKf'), designated as increment incrementpK, records changes in the electrostatic potential at the binding site has been examined in spectrophotometric and binding experiments, using the interaction of Chlorophenol Red and Phenol Red with human serum albumin and cationic micelles as examples. (1) In serum albumin solutions increment incrementpK is decreased by a reduction of pH. The decrease is correlated with the increase in positive charges on the protein molecule, and the response is attenuated by high ionic strength in accordance with electrostatic theory. (2) Opposite changes in binding affinity to serum albumin and increment incrementpK as a function of pH are observed; the binding of basic (bivalent anion) dye is more susceptible to a change in pH than in the acidic (univalent anion) form. (3) Preferential uptake of the basic as compared to the acidic form of dye is observed by binding to cetyltrimethylammonium chloride and cetylpyridinium chloride micelles (mu equals 0.033, [Cl-] equals 0.033 M). An increase in the ionic strength is accompanied by a positive value of increment incrementpK. The results are consonant with the view that the observed increment incrementpK values reflect changes in the electrostatic potential at the binding site with consequently little, if any, effect on the intrinsic pK. The extension of the method to measure changes in the electrostatic potential at binding sites on cell membranes is briefly discussed.", "contents": "Indicator dyes as probes of electrostatic potential changes on macromolecular surfaces. An indicator dye attached to an electrostatically charged macromolecular surface generally has a pK value (pKb') different from that of uncombined dye (pKf'). The question if changes in (pKb' - pKf'), designated as increment incrementpK, records changes in the electrostatic potential at the binding site has been examined in spectrophotometric and binding experiments, using the interaction of Chlorophenol Red and Phenol Red with human serum albumin and cationic micelles as examples. (1) In serum albumin solutions increment incrementpK is decreased by a reduction of pH. The decrease is correlated with the increase in positive charges on the protein molecule, and the response is attenuated by high ionic strength in accordance with electrostatic theory. (2) Opposite changes in binding affinity to serum albumin and increment incrementpK as a function of pH are observed; the binding of basic (bivalent anion) dye is more susceptible to a change in pH than in the acidic (univalent anion) form. (3) Preferential uptake of the basic as compared to the acidic form of dye is observed by binding to cetyltrimethylammonium chloride and cetylpyridinium chloride micelles (mu equals 0.033, [Cl-] equals 0.033 M). An increase in the ionic strength is accompanied by a positive value of increment incrementpK. The results are consonant with the view that the observed increment incrementpK values reflect changes in the electrostatic potential at the binding site with consequently little, if any, effect on the intrinsic pK. The extension of the method to measure changes in the electrostatic potential at binding sites on cell membranes is briefly discussed."}
{"id": "PMID:237530", "title": "Catalysis of phosphoryl group transfer. The role of divalent metal ions in the hydrolysis of lactic acid O-phenyl phosphate and salicylic acid O-aryl phosphates.", "content": "The spontaneous hydrolyses of lactic acid O-phenyl phosphate (I) and, to a lesser extent, 3-hydroxybutyric acid O-phenyl phosphate (II) have been investigated and compared with similar intramolecular and bimolecular reactions. Compared to bimolecular nucleophilic reactions, the reactivity of II is similar to other systems involving the formation of a six-membered ring intermediate, which suggests that the electrostatic barrier to attack of an anionic nucleophile on a phosphate diester anion is fully present in II. The reactivity of I, as compared to that of II, would suggest that at least a partial overcoming of the electrostatic barrier takes place upon closer approimation of the two reacting centers. The Mn-2+-catalyzed hydrolysis of I exhibits saturation kinetics, consistent with the enhanced reactivity of the metal ion-substrate complex. The binding constant for this complex, determined from kinetics, is in good agreement with that obtained by electron spin resonance (ESR) titration. It is argued that the complex of Mn-2+ with II, as observed by pulsed Fourier transform nuclear magnetic resonance (NMR) techniques, is a precursor to the complex of catalytic significance. The hydrolysis of I as catalyzed by a variety of divalent metal ions suggests an optimal metal ion size. The spontaneous and metal ion catalyzed hydrolyses of salicyclic acid O-aryl phosphates (IIIa-d) proceed through cyclic acyl phosphate intermediates after expulsion of phenol. Product studies on the parent compound have failed to detect phenyl phosphate as a product in either the spontaneous or metal ion catalyzed process. The dependence of the second-order rate constant for the metal-catalyzed hydrolysis on leaving group pKa, beta-1-g, decreases significantly relative to beta-1-g for the spontaneous hydrolysis. From the collective data a specific interation of the metal ion with a pentacovalent intermediate is inferred in the rate-determining step for esters I and III. The probable consequences of these mechanistic postulates for phosphoryl transfer reactions in biological systems are discussed.", "contents": "Catalysis of phosphoryl group transfer. The role of divalent metal ions in the hydrolysis of lactic acid O-phenyl phosphate and salicylic acid O-aryl phosphates. The spontaneous hydrolyses of lactic acid O-phenyl phosphate (I) and, to a lesser extent, 3-hydroxybutyric acid O-phenyl phosphate (II) have been investigated and compared with similar intramolecular and bimolecular reactions. Compared to bimolecular nucleophilic reactions, the reactivity of II is similar to other systems involving the formation of a six-membered ring intermediate, which suggests that the electrostatic barrier to attack of an anionic nucleophile on a phosphate diester anion is fully present in II. The reactivity of I, as compared to that of II, would suggest that at least a partial overcoming of the electrostatic barrier takes place upon closer approimation of the two reacting centers. The Mn-2+-catalyzed hydrolysis of I exhibits saturation kinetics, consistent with the enhanced reactivity of the metal ion-substrate complex. The binding constant for this complex, determined from kinetics, is in good agreement with that obtained by electron spin resonance (ESR) titration. It is argued that the complex of Mn-2+ with II, as observed by pulsed Fourier transform nuclear magnetic resonance (NMR) techniques, is a precursor to the complex of catalytic significance. The hydrolysis of I as catalyzed by a variety of divalent metal ions suggests an optimal metal ion size. The spontaneous and metal ion catalyzed hydrolyses of salicyclic acid O-aryl phosphates (IIIa-d) proceed through cyclic acyl phosphate intermediates after expulsion of phenol. Product studies on the parent compound have failed to detect phenyl phosphate as a product in either the spontaneous or metal ion catalyzed process. The dependence of the second-order rate constant for the metal-catalyzed hydrolysis on leaving group pKa, beta-1-g, decreases significantly relative to beta-1-g for the spontaneous hydrolysis. From the collective data a specific interation of the metal ion with a pentacovalent intermediate is inferred in the rate-determining step for esters I and III. The probable consequences of these mechanistic postulates for phosphoryl transfer reactions in biological systems are discussed."}
{"id": "PMID:237531", "title": "Renilla luciferin as the substrate for calcium induced photoprotein bioluminescence. Assignment of luciferin tautomers in aequorin and mnemiopsin.", "content": "A study was made of the effects of pH and protic and aprotic solvents on the spectral properties of Renilla (sea pansy) luciferin and a number of its analogs. The results have made possible the assignment of two tautomeric forms of Renilla luciferin, one which absorbs maximally at 435 nm and another which exhibits an absorption maximum at 454 nm. Furthermore the results provide an explanation for the visible absorption characteristics of the photoproteins aequorin (lambda-max 454 nm) and mnemiopsin (lambda-max 435 nm). In addition a Renilla-like luciferin can be extracted from both of these photoproteins. This luciferin produces light with Renilla luciferase, at a rate dependent upon the concentration of dissolved oxygen, and in other respects is indistinguishable from Renilla luciferin in this bioluminescent reaction. The results suggest that the native chromophore in both photoproteins is Renilla luciferin (or a nearly identical derivative). The results also suggest that a hydroperoxide intermediate probably exists in photoproteins, on energetic grounds, and to account for the oxygen concentration independency of the rate of photoprotein reactions. This hydroperoxide may be attached initially to an amino-acid side chain (possibly indolyl-OOH, imidazoyl-OOH, or -SOOH) rather than to the luciferin chromophore.", "contents": "Renilla luciferin as the substrate for calcium induced photoprotein bioluminescence. Assignment of luciferin tautomers in aequorin and mnemiopsin. A study was made of the effects of pH and protic and aprotic solvents on the spectral properties of Renilla (sea pansy) luciferin and a number of its analogs. The results have made possible the assignment of two tautomeric forms of Renilla luciferin, one which absorbs maximally at 435 nm and another which exhibits an absorption maximum at 454 nm. Furthermore the results provide an explanation for the visible absorption characteristics of the photoproteins aequorin (lambda-max 454 nm) and mnemiopsin (lambda-max 435 nm). In addition a Renilla-like luciferin can be extracted from both of these photoproteins. This luciferin produces light with Renilla luciferase, at a rate dependent upon the concentration of dissolved oxygen, and in other respects is indistinguishable from Renilla luciferin in this bioluminescent reaction. The results suggest that the native chromophore in both photoproteins is Renilla luciferin (or a nearly identical derivative). The results also suggest that a hydroperoxide intermediate probably exists in photoproteins, on energetic grounds, and to account for the oxygen concentration independency of the rate of photoprotein reactions. This hydroperoxide may be attached initially to an amino-acid side chain (possibly indolyl-OOH, imidazoyl-OOH, or -SOOH) rather than to the luciferin chromophore."}
{"id": "PMID:237532", "title": "Essential and nonessential thiols of yeast hexokinase. Reactions with iodoacetate and iodoacetamide.", "content": "The reaction of yeast hexokinase with iodoacetate or iodoacetamide has been investigated in detail, using pure hexodinase B. Of the four thiols in each subunit of the molecule, two (the \"apparently essential thiols\") are alkylated rapidly at 35 degrees, and the enzymic activity is lost in parallel with their reaction. The other two thiols react subsequently to completion, but at a very much slower rate. In the conditions use, no other uptake of the reagent occurs elsewhere during these thiol alkylations. Electrophoretically homogeneous kialkylated and tetraalkylated protein species are formed, in the two stages of the reaction. The inactivating reaction at 35 degrees with the apparently essential thiols is second order. The rate constant increases with increasing pH, in the range pH 7.0-8.5, in a manner consistent with control of the reaction by a group with pKa of approximately 10. The absolute (pH independent) rate constant is of the same order as that for a normal thiol in model compounds. The availability of the apparently essential thiols appears to be associated with some conformational change in the molecule in the monomer form: it declines at high ionic strengths, is maximal at intermediate values where the dimer first dissociates, but is lowered in the dimer at very low ionic strengths. The reaction also shows a sharp temperature dependence: the dimer at 30 degrees (in constrast to 35 degrees) shows no availability of the apparently essential thiols. A similar transition to a state permitting fast inactivation is found with pH, above pH 8.5. The reaction of the two apparently essential thiols is strongly inhibited by glucose. ATP and ADP, and their Mg complexes, protect significantly, but less effectively than does glucose. The affinities of these substrates at the active site of the enzyme are measured in this protection system. These various reactions appear to be of value for identifying the cysteine-containing regions that are involved in the active center or in its maintenance in the structure.", "contents": "Essential and nonessential thiols of yeast hexokinase. Reactions with iodoacetate and iodoacetamide. The reaction of yeast hexokinase with iodoacetate or iodoacetamide has been investigated in detail, using pure hexodinase B. Of the four thiols in each subunit of the molecule, two (the \"apparently essential thiols\") are alkylated rapidly at 35 degrees, and the enzymic activity is lost in parallel with their reaction. The other two thiols react subsequently to completion, but at a very much slower rate. In the conditions use, no other uptake of the reagent occurs elsewhere during these thiol alkylations. Electrophoretically homogeneous kialkylated and tetraalkylated protein species are formed, in the two stages of the reaction. The inactivating reaction at 35 degrees with the apparently essential thiols is second order. The rate constant increases with increasing pH, in the range pH 7.0-8.5, in a manner consistent with control of the reaction by a group with pKa of approximately 10. The absolute (pH independent) rate constant is of the same order as that for a normal thiol in model compounds. The availability of the apparently essential thiols appears to be associated with some conformational change in the molecule in the monomer form: it declines at high ionic strengths, is maximal at intermediate values where the dimer first dissociates, but is lowered in the dimer at very low ionic strengths. The reaction also shows a sharp temperature dependence: the dimer at 30 degrees (in constrast to 35 degrees) shows no availability of the apparently essential thiols. A similar transition to a state permitting fast inactivation is found with pH, above pH 8.5. The reaction of the two apparently essential thiols is strongly inhibited by glucose. ATP and ADP, and their Mg complexes, protect significantly, but less effectively than does glucose. The affinities of these substrates at the active site of the enzyme are measured in this protection system. These various reactions appear to be of value for identifying the cysteine-containing regions that are involved in the active center or in its maintenance in the structure."}
{"id": "PMID:237533", "title": "Superactivation of thermolysin by acylation with amino acid N-hydroxysuccinimide esters.", "content": "Synthesis of a series of active N-hydroxysuccinimide esters of aliphatic and aromatic amino acids has yielded a new class of reagents for the covalent modification of proteolytic enzymes such as thermolysin. The activities of aliphatic acyl amino acid thermolysins are from 1.7 to 3.6 times greater than that of the native enzyme when hydrolyzing durylacryloyl-Gly-Leu-NH2, the substrate employed most widely. By comparison, the aromatic acylamino acid derivatives are \"superactive,\" their activities being as much as 70-fold greater. Apparently, the aromatic character of the amino acid introduced is a critical variable in the determination of the functional response. The increased activity is completely restored to that of the native enzyme by deacylation with nucleophiles, such as hydroxylamine, and the rate of restoration of native activity is a function of the particular acyl group incorporated. Preliminary evidence regarding the chemical properties of the modified enzyme suggests that tyrosine, rather than lysine, histidine, or arginine, may be the residue modified. The functional consequences of successive modification with different reagents, moreover, indicate that each of them reacts with the same protein residue. The competitive inhibitors beta-phenyl-propionyl-Phe and Zn-2+ do not prevent modification with these active esters. Hence, the site(s) of their inhibitory action differ(s) from that at which modification occurs. The structure of the substrate is also a significant variable which determines the rate at which each acyl amino acid thermolysin hydrolyzes peptides. Depending on the particular substrate, the activity of aromatic derivatives can be as much as 400-fold greater than that of the native enzyme, and the resultant activity patterns can be ordered in a series characteristic for each enzyme derivative.", "contents": "Superactivation of thermolysin by acylation with amino acid N-hydroxysuccinimide esters. Synthesis of a series of active N-hydroxysuccinimide esters of aliphatic and aromatic amino acids has yielded a new class of reagents for the covalent modification of proteolytic enzymes such as thermolysin. The activities of aliphatic acyl amino acid thermolysins are from 1.7 to 3.6 times greater than that of the native enzyme when hydrolyzing durylacryloyl-Gly-Leu-NH2, the substrate employed most widely. By comparison, the aromatic acylamino acid derivatives are \"superactive,\" their activities being as much as 70-fold greater. Apparently, the aromatic character of the amino acid introduced is a critical variable in the determination of the functional response. The increased activity is completely restored to that of the native enzyme by deacylation with nucleophiles, such as hydroxylamine, and the rate of restoration of native activity is a function of the particular acyl group incorporated. Preliminary evidence regarding the chemical properties of the modified enzyme suggests that tyrosine, rather than lysine, histidine, or arginine, may be the residue modified. The functional consequences of successive modification with different reagents, moreover, indicate that each of them reacts with the same protein residue. The competitive inhibitors beta-phenyl-propionyl-Phe and Zn-2+ do not prevent modification with these active esters. Hence, the site(s) of their inhibitory action differ(s) from that at which modification occurs. The structure of the substrate is also a significant variable which determines the rate at which each acyl amino acid thermolysin hydrolyzes peptides. Depending on the particular substrate, the activity of aromatic derivatives can be as much as 400-fold greater than that of the native enzyme, and the resultant activity patterns can be ordered in a series characteristic for each enzyme derivative."}
{"id": "PMID:237534", "title": "Hormonal regulation of fatty acid synthetase, acetyl-CoA carboxylase and fatty acid synthesis in mammalian adipose tissue and liver.", "content": "The major objectives of this study were to define the roles of adrenal glucocorticoids and glucagon in the long-term regulation of fatty acid synthetase and acetyl-CoA carboxylase of mammalian adipose tissue and liver. Particular emphasis was given to elucidation of the mechanisms whereby these hormones produce their regulatory effects on enzymatic activity. To dissociate mental manipulation, nutritional conditions were ridgidly controlled in the experiments described. Administration of glucocorticoids to adult rats led to a marked reductionin activities of fatty acid synthetase and carboxylase in adipose in adipose tissue but no change occurred in liver. Adrenalectomy produced an increase in activities of these lipogenic enzymes in adipose tissure, but, again, no change was noted in liver. The decrease in enzymatic activities in adipose tissue with glucocorticoid administration correlated well with a decrease in fatty acid synthesis, determined in vivo by the 3-H2O method. The mechanisms whereby glucocorticoids led to a decrease in fatty acid synthetase activity were elucidated by the use of immunochemical techniques. Thus, the decrease in fatty acid synthetase activity observed in adipose tissue was shown to reflect a decrease in content of enzyme, and not a change in catalytic efficiency. The mechanism underlying the decrease in enzyme content is a decrease in synthesis of the enzyme. The relation of the effects of glucocorticoids to the effects of certain other hormones involved in regulation of lipogenesis was investigated in hypophysectomized and in diabetic animals. Thus, the observation that the glucocorticoid effect on synthetase and carboxylase occurred in adipose tissue of hypophysectomized rats indicated that alterations in levels of other pituitary-regulated hormones were not necessary for the effect. That glucocorticoids play some role in regulation of synthetase and carboxylase in liver, at lease in the diabetic state, was shown by the observation that the low activities of these enzymes in diabetic animals could be restored to normal by adrenalectomy. An even more pronounced restorative effect was apparent in adipose tissue of adrenalectomized, diabetic animals. Administration of glucagon during the refeeding of starved rats resulted in a marked reduction in the induction of fatty acid synthetase, acetyl-CoA carboxylase and in the rate of incorporation of 3-H from 3-H2O into fatty acids in liver, but no change in these parameters occurred in adipose tissue. Administration of theophylline resulted in intermediate reduction in liver. The mechanisms whereby glucagon led tto a decrease in fatty acid synthetase activity were elucidated by the use of immunochemical techniques. Thus, the changes in fatty acid synthetase activity were shown to reflect reductions in content of enzyme. The mechanism underlying these reductions in content is reduced synthesis of enzyme.", "contents": "Hormonal regulation of fatty acid synthetase, acetyl-CoA carboxylase and fatty acid synthesis in mammalian adipose tissue and liver. The major objectives of this study were to define the roles of adrenal glucocorticoids and glucagon in the long-term regulation of fatty acid synthetase and acetyl-CoA carboxylase of mammalian adipose tissue and liver. Particular emphasis was given to elucidation of the mechanisms whereby these hormones produce their regulatory effects on enzymatic activity. To dissociate mental manipulation, nutritional conditions were ridgidly controlled in the experiments described. Administration of glucocorticoids to adult rats led to a marked reductionin activities of fatty acid synthetase and carboxylase in adipose in adipose tissue but no change occurred in liver. Adrenalectomy produced an increase in activities of these lipogenic enzymes in adipose tissure, but, again, no change was noted in liver. The decrease in enzymatic activities in adipose tissue with glucocorticoid administration correlated well with a decrease in fatty acid synthesis, determined in vivo by the 3-H2O method. The mechanisms whereby glucocorticoids led to a decrease in fatty acid synthetase activity were elucidated by the use of immunochemical techniques. Thus, the decrease in fatty acid synthetase activity observed in adipose tissue was shown to reflect a decrease in content of enzyme, and not a change in catalytic efficiency. The mechanism underlying the decrease in enzyme content is a decrease in synthesis of the enzyme. The relation of the effects of glucocorticoids to the effects of certain other hormones involved in regulation of lipogenesis was investigated in hypophysectomized and in diabetic animals. Thus, the observation that the glucocorticoid effect on synthetase and carboxylase occurred in adipose tissue of hypophysectomized rats indicated that alterations in levels of other pituitary-regulated hormones were not necessary for the effect. That glucocorticoids play some role in regulation of synthetase and carboxylase in liver, at lease in the diabetic state, was shown by the observation that the low activities of these enzymes in diabetic animals could be restored to normal by adrenalectomy. An even more pronounced restorative effect was apparent in adipose tissue of adrenalectomized, diabetic animals. Administration of glucagon during the refeeding of starved rats resulted in a marked reduction in the induction of fatty acid synthetase, acetyl-CoA carboxylase and in the rate of incorporation of 3-H from 3-H2O into fatty acids in liver, but no change in these parameters occurred in adipose tissue. Administration of theophylline resulted in intermediate reduction in liver. The mechanisms whereby glucagon led tto a decrease in fatty acid synthetase activity were elucidated by the use of immunochemical techniques. Thus, the changes in fatty acid synthetase activity were shown to reflect reductions in content of enzyme. The mechanism underlying these reductions in content is reduced synthesis of enzyme."}
{"id": "PMID:237535", "title": "A simple and high yield purification of Crotalus adamanteus phospholipases A2.", "content": "A new, high yield, procedure for the purification of the phospholipases A2 of Crotalus adamanteus venom is described. The procedure involves precipitation of the bulk of venom proteins with 50% isopropanol, precipitation of the enzymes from the isopranol soluble material with neodynium chloride, and final purification on DEAE cellulose. An overall yield of approximately 80% is achieved.", "contents": "A simple and high yield purification of Crotalus adamanteus phospholipases A2. A new, high yield, procedure for the purification of the phospholipases A2 of Crotalus adamanteus venom is described. The procedure involves precipitation of the bulk of venom proteins with 50% isopropanol, precipitation of the enzymes from the isopranol soluble material with neodynium chloride, and final purification on DEAE cellulose. An overall yield of approximately 80% is achieved."}
{"id": "PMID:237536", "title": "Affinity chromatography on hydroxyalkyl methacrylate gels. II. Isolation of thiol-containing protein and peptide using mercurial derivatives of gels.", "content": "Absorption properties of hydroxyalkyl methacrylate gels containing various amounts of mercuri derivatives of p-acetaminophenoxyethyl methacrylates (Hg-APEMA) and methacrylanilide (Hg-MAA) were investigated by means of a reduced Ellman's agent (5,5'-dithiobis-2-nitrobenzoic acid) and papain. The optimum gel was used for the affinity chromatography of SH-protease from beans and for the isolation of a peptide with a free sulphhydryl group from the chymotryptic hydrolyzate of serum albumin.", "contents": "Affinity chromatography on hydroxyalkyl methacrylate gels. II. Isolation of thiol-containing protein and peptide using mercurial derivatives of gels. Absorption properties of hydroxyalkyl methacrylate gels containing various amounts of mercuri derivatives of p-acetaminophenoxyethyl methacrylates (Hg-APEMA) and methacrylanilide (Hg-MAA) were investigated by means of a reduced Ellman's agent (5,5'-dithiobis-2-nitrobenzoic acid) and papain. The optimum gel was used for the affinity chromatography of SH-protease from beans and for the isolation of a peptide with a free sulphhydryl group from the chymotryptic hydrolyzate of serum albumin."}
{"id": "PMID:237537", "title": "Partial purification and characterization of the enzyme which converts precursor liver protein to factor X.", "content": "A rat liver post-microsomal supernatant enzyme, which carries out an epigenetic conversion of a protein contained in liver microsomes to Factor X, has been partially purified 250-fold in 50% yield by a combination of salt fractionation and gel filtration. The crude enzyme is stable to freezing and thawing but unstable at 4 degrees C. However, the partially purified enzyme is more stable at 4 degrees C. It requires Ca2+ and HCO3 minus for optimum formation of Factor X activity. The supernatant enzyme is vitamin K dependent and exhibits its maximum rate of formation of Factor X between pH 8 and 8.5.", "contents": "Partial purification and characterization of the enzyme which converts precursor liver protein to factor X. A rat liver post-microsomal supernatant enzyme, which carries out an epigenetic conversion of a protein contained in liver microsomes to Factor X, has been partially purified 250-fold in 50% yield by a combination of salt fractionation and gel filtration. The crude enzyme is stable to freezing and thawing but unstable at 4 degrees C. However, the partially purified enzyme is more stable at 4 degrees C. It requires Ca2+ and HCO3 minus for optimum formation of Factor X activity. The supernatant enzyme is vitamin K dependent and exhibits its maximum rate of formation of Factor X between pH 8 and 8.5."}
{"id": "PMID:237538", "title": "Comparative study on conformational stability and subunit interactions of two bacterial asparaginases.", "content": "The denaturation and reconstitution of Erwinia carotovora and Escherichia coli L-asparaginases has been followed by optical rotatory dispersion, circular dichroism and analytical ultracentrifugation. Denaturation in urea results in dissociation of the native enzyme (mol. wt. 140 000 approx.) to produce unfolded subunits (mol. wt. 35 000 approx.); the Erwinia L-asparaginase subunits can be refolded by dilution or dialysis in alkaline conditions, pH 10.5, without aggregation to the active tetramer, to give a rather unstable solution of a monomer possibly in equilibrium with dimer. These alkaline-reconstituted subunits undergo a conformational change to a more ordered state in the presence of sodium dodecylsulphate, similar to those produced by the action of sodium dodecylsulphate on the native enzyme. If the denatured subunits are reconstituted in the pH range 5.0-7.5, the enzymically active tetramer is reformed in up to 80% yield, depending upon the conditions of temperature and concentration. Kinetic data for these various transitions suggest that dissociation is a rate-limiting step while conformational changes of the polypeptide chains are relatively much more rapid. The possible significance of these different rates of change to therapeutic considerations is discussed.", "contents": "Comparative study on conformational stability and subunit interactions of two bacterial asparaginases. The denaturation and reconstitution of Erwinia carotovora and Escherichia coli L-asparaginases has been followed by optical rotatory dispersion, circular dichroism and analytical ultracentrifugation. Denaturation in urea results in dissociation of the native enzyme (mol. wt. 140 000 approx.) to produce unfolded subunits (mol. wt. 35 000 approx.); the Erwinia L-asparaginase subunits can be refolded by dilution or dialysis in alkaline conditions, pH 10.5, without aggregation to the active tetramer, to give a rather unstable solution of a monomer possibly in equilibrium with dimer. These alkaline-reconstituted subunits undergo a conformational change to a more ordered state in the presence of sodium dodecylsulphate, similar to those produced by the action of sodium dodecylsulphate on the native enzyme. If the denatured subunits are reconstituted in the pH range 5.0-7.5, the enzymically active tetramer is reformed in up to 80% yield, depending upon the conditions of temperature and concentration. Kinetic data for these various transitions suggest that dissociation is a rate-limiting step while conformational changes of the polypeptide chains are relatively much more rapid. The possible significance of these different rates of change to therapeutic considerations is discussed."}
{"id": "PMID:237539", "title": "Binding of D-glucose to insulin.", "content": "Binding of D-glucose to insulin has been studied by equilibrium dialysis. The binding is not very specific and probably takes place in two steps. The average amount of glucose molecules bound per insulin molecule is eight, two molecules in the first and six during the second step of binding. The intrinsic binding constants for both steps are almost the same (6-10-2 M-minus 1 and 1-10-3 M-minus 1) which can be explained by assuming: (1) that after binding of the first two molecules a conformational change of insulin occurs which facilitates the binding of the next six molecules of D-glucose; or (2) that in the second step of binding the glucose binds to hydrophobic regions which are unmasked by dissociation of the insulin dimer. Using a three-dimensional model of the insulin molecule areas of the protein molecule where binding of glucose can occur were selected. The glucose-binding site very probably involves the area at the insulin surface where most of the invariant and modification-selective residues are present.", "contents": "Binding of D-glucose to insulin. Binding of D-glucose to insulin has been studied by equilibrium dialysis. The binding is not very specific and probably takes place in two steps. The average amount of glucose molecules bound per insulin molecule is eight, two molecules in the first and six during the second step of binding. The intrinsic binding constants for both steps are almost the same (6-10-2 M-minus 1 and 1-10-3 M-minus 1) which can be explained by assuming: (1) that after binding of the first two molecules a conformational change of insulin occurs which facilitates the binding of the next six molecules of D-glucose; or (2) that in the second step of binding the glucose binds to hydrophobic regions which are unmasked by dissociation of the insulin dimer. Using a three-dimensional model of the insulin molecule areas of the protein molecule where binding of glucose can occur were selected. The glucose-binding site very probably involves the area at the insulin surface where most of the invariant and modification-selective residues are present."}
{"id": "PMID:237540", "title": "Mechanism of respiration-driven proton translocation in the inner mitochondrial membrane. Analysis of proton translocation associated with oxidation of endogenous ubiquinol.", "content": "A study is presented of the kinetics and stoichiometry of fast proton translocation associated to aerobic oxidation of components of the mitochondrial respiratory chain. 1. Aerobic oxidation of ubiquinol and b cytochromes is accompanied in EDTA particles, obtained by sonication of beef-heart mitochondria, by synchronous proton uptake. 2. The rapid proton uptake associated to oxidation and b cytochromes is greatly stimulated by valinomycin plus K+, but is unaffected by carbonyl cyanide p-trifluoromethoxyphenylhydrazone. 3. 4 gion H+ are taken up per mol ubiquinol oxidized by oxygen. This H+/2e- ratio, measured in the rapid anaerobic-aerobic transition of the particles is unaffected by carbonyl cyanide p-trifluoromethoxyphenylhydrazone. 4. Intact mitochondria aerobic oxidation of oxygen-terminal electron carriers is accompanied by antimycin-insensitive synchronous proton release, oxidation of ubiquinol and reduction of b cytochromes. The amount of protons released is in excess with respect to the amount of ubiquinol oxidized. 5. It is concluded that electron flow along complex III, from ubiquinol to cytochrome c, is directly coupled to vectorial proton translocation. The present data suggest that there exist(s) between ubiquinol and cytochrome c one (or two) respiratory carrier(s), whose oxido-reduction is directly linked to effective transmembrane proton translocation.", "contents": "Mechanism of respiration-driven proton translocation in the inner mitochondrial membrane. Analysis of proton translocation associated with oxidation of endogenous ubiquinol. A study is presented of the kinetics and stoichiometry of fast proton translocation associated to aerobic oxidation of components of the mitochondrial respiratory chain. 1. Aerobic oxidation of ubiquinol and b cytochromes is accompanied in EDTA particles, obtained by sonication of beef-heart mitochondria, by synchronous proton uptake. 2. The rapid proton uptake associated to oxidation and b cytochromes is greatly stimulated by valinomycin plus K+, but is unaffected by carbonyl cyanide p-trifluoromethoxyphenylhydrazone. 3. 4 gion H+ are taken up per mol ubiquinol oxidized by oxygen. This H+/2e- ratio, measured in the rapid anaerobic-aerobic transition of the particles is unaffected by carbonyl cyanide p-trifluoromethoxyphenylhydrazone. 4. Intact mitochondria aerobic oxidation of oxygen-terminal electron carriers is accompanied by antimycin-insensitive synchronous proton release, oxidation of ubiquinol and reduction of b cytochromes. The amount of protons released is in excess with respect to the amount of ubiquinol oxidized. 5. It is concluded that electron flow along complex III, from ubiquinol to cytochrome c, is directly coupled to vectorial proton translocation. The present data suggest that there exist(s) between ubiquinol and cytochrome c one (or two) respiratory carrier(s), whose oxido-reduction is directly linked to effective transmembrane proton translocation."}
{"id": "PMID:237541", "title": "Surface potential and the interaction of weakly acidic uncouplers of oxidative phosphorylation with liposomes and mitochondria.", "content": "The pH dependence of the binding of weakly acidic uncouplers of oxidative phosphorylation to rat-liver mitochondria and liposomes is mainly determined by the pKa of the uncoupler molecule. The absorption and fluorescene excitation spectra of the anionic form of weakly acidic uncouplers of oxidative phosphorylation are red-shifted upon interaction with liposomal or mitochondrial membranes. The affinity for the liposomes, as deduced from the red shift, is independent of the degree of saturation of the fatty acid chains of different lecithins. The intensity of the spectra at one pH value is strongly dependent upon the surface charge of the liposomes. With positively charged liposomes the results obtained can be almost quantitatively explained with the Gouy-Chapman theory, but with negatively charged ones deviations are observed. At a particular pH, the divalent ion Ca-2+ stongly influences the intensity of the spectra in the presence of negatively charged liposomes, but has no effect with neutral liposomes. With mitochondrial membranes an effect of Ca-2+ similar to that with negatively charged liposomes is observed. Depletion of the phospholipids of the mitochondria and subsequent restoration of the mitochrondrial membrane with lecithin, strongly diminishes this effect, but restoration with negatively charged phospholipids does not influence it. From these observations it is concluded that the anionic form of the uncoupler molecule when bound to mitochondria is located within the partly negatively charged phospholiped moiety of the membrane, with its anionic group pointing to the aqueous solution.", "contents": "Surface potential and the interaction of weakly acidic uncouplers of oxidative phosphorylation with liposomes and mitochondria. The pH dependence of the binding of weakly acidic uncouplers of oxidative phosphorylation to rat-liver mitochondria and liposomes is mainly determined by the pKa of the uncoupler molecule. The absorption and fluorescene excitation spectra of the anionic form of weakly acidic uncouplers of oxidative phosphorylation are red-shifted upon interaction with liposomal or mitochondrial membranes. The affinity for the liposomes, as deduced from the red shift, is independent of the degree of saturation of the fatty acid chains of different lecithins. The intensity of the spectra at one pH value is strongly dependent upon the surface charge of the liposomes. With positively charged liposomes the results obtained can be almost quantitatively explained with the Gouy-Chapman theory, but with negatively charged ones deviations are observed. At a particular pH, the divalent ion Ca-2+ stongly influences the intensity of the spectra in the presence of negatively charged liposomes, but has no effect with neutral liposomes. With mitochondrial membranes an effect of Ca-2+ similar to that with negatively charged liposomes is observed. Depletion of the phospholipids of the mitochondria and subsequent restoration of the mitochrondrial membrane with lecithin, strongly diminishes this effect, but restoration with negatively charged phospholipids does not influence it. From these observations it is concluded that the anionic form of the uncoupler molecule when bound to mitochondria is located within the partly negatively charged phospholiped moiety of the membrane, with its anionic group pointing to the aqueous solution."}
{"id": "PMID:237542", "title": "Some biochemical and physiochemical properties of the potent uncoupler SF 6847 (3,5-di-tert-butyl-4-hydroxybenzylidenemalononitrile).", "content": "Various physicochemical and biochemical properties of the most potent uncoupler of oxidative phosphorylation known to date 3,5-di-tert-butyl-4-hydroxybenzylidenemalononitrile (SF 6847), such as pH dependence of the uncoupling activity and binding to mitochondria, spectral properties in the presence of different types of liposomes, biopolymers and mitochondria, and effects on model membrane systems have been investigated. From the results, it is concluded that the uncoupler most likely is localized in the phospholipid part of the membrane.", "contents": "Some biochemical and physiochemical properties of the potent uncoupler SF 6847 (3,5-di-tert-butyl-4-hydroxybenzylidenemalononitrile). Various physicochemical and biochemical properties of the most potent uncoupler of oxidative phosphorylation known to date 3,5-di-tert-butyl-4-hydroxybenzylidenemalononitrile (SF 6847), such as pH dependence of the uncoupling activity and binding to mitochondria, spectral properties in the presence of different types of liposomes, biopolymers and mitochondria, and effects on model membrane systems have been investigated. From the results, it is concluded that the uncoupler most likely is localized in the phospholipid part of the membrane."}
{"id": "PMID:237543", "title": "Cytochrome c2 and reaction center of Rhodospeudomonas spheroides Ga. membranes. Extinction coefficients, content, half-reduction potentials, kinetics and electric field alterations.", "content": "The reduced minus oxidized extinction coefficients (delta epsilon-red-ox) of reaction center P605 when in the chromatophore is about 20% smaller than in the detergent-isolated state. Presumably the coupling of the reaction center protein to the antenna bacteriochlorophylls and carotenoids causes this hypochromism. The chromatophore values for P605 are 19.5 mM- minus 1 times cm- minus 1 with the spectrophotometer on single beam mode at 605 nm, and 29.8 mM- minus 1 times cm- minus 1 on dual wavelength mode set at 605--540 nm. Cytochrome c2, which is not affected by detergent, has a delta epsilon-red-ox value at 550--540 nm of 19.0 mM- minus 1 times cm- minus 1.2. The total bacteriochlorophyll to reaction center bacteriochlorophyll protein (P) ratio is about 100: 1. The cytochrome c2: reaction center protein ratio approaches 2. In current French press chromatophore preparations, about 70% of the reaction centers are each associated on a rapid kinetic basis with two cytochrome c2 molecules (intact P-c2 units). The remaining reaction center proteins are not associated with cytochrome c2 on a kinetically viable bais and may be the result of damage incurred during mechanical rupture of the cells. 3...", "contents": "Cytochrome c2 and reaction center of Rhodospeudomonas spheroides Ga. membranes. Extinction coefficients, content, half-reduction potentials, kinetics and electric field alterations. The reduced minus oxidized extinction coefficients (delta epsilon-red-ox) of reaction center P605 when in the chromatophore is about 20% smaller than in the detergent-isolated state. Presumably the coupling of the reaction center protein to the antenna bacteriochlorophylls and carotenoids causes this hypochromism. The chromatophore values for P605 are 19.5 mM- minus 1 times cm- minus 1 with the spectrophotometer on single beam mode at 605 nm, and 29.8 mM- minus 1 times cm- minus 1 on dual wavelength mode set at 605--540 nm. Cytochrome c2, which is not affected by detergent, has a delta epsilon-red-ox value at 550--540 nm of 19.0 mM- minus 1 times cm- minus 1.2. The total bacteriochlorophyll to reaction center bacteriochlorophyll protein (P) ratio is about 100: 1. The cytochrome c2: reaction center protein ratio approaches 2. In current French press chromatophore preparations, about 70% of the reaction centers are each associated on a rapid kinetic basis with two cytochrome c2 molecules (intact P-c2 units). The remaining reaction center proteins are not associated with cytochrome c2 on a kinetically viable bais and may be the result of damage incurred during mechanical rupture of the cells. 3..."}
{"id": "PMID:237545", "title": "Biochemical changes in Bifidobacterium bifidum var. pennsylvanicus after cell wall inhibition. VIII. Composition and metabolism of phospholipids at different stages and conditions of growth.", "content": "1. The phospholipid content and composition of Bifidobacterium bifidum var. pennsylvanicus is markedly influenced by the growth phase, the pH and the presence of human milk in the culture medium. 2. The lipid-phosphorus content of the cells increases during the first period of active growth, but decreases later. The lipid-phosphorus content of the cells in the stationary phase is at constant pH 5.5 about 45 percent of that at constant pH 6.8 and final pH 5.2. This difference is caused by a general reduction of all types of phospholipids. 3. Phosphatidylglycerol content decreases during growth, diphosphatidylglycerol increases in the first period, but decreases later and especially in the stationary phase by an increase of its lysoderivatives. The phosphogalactolipids rise during growth in the non-controlled pH-culture to 70 percent of the phospholipids in the stationary phase. When pH is constant at 6.8 and 5.5 glycerolphosphorylgalactosyldiglyceride remains at a constant level of about 20 percent during growth. At pH 6.8 glycerophosphorylmonogalactosylmonoglyceride increases to 24 percent during cultivation; at pH 5.5 this lipid contributes only a few percent. 4. Under all pH conditions, lack of human milk in the culture medium causes a marked increase of the lipid-phosphorus content of the cell, together with a high increase of the relative amounts of diphosphatidylglycerol and phosphatidylglycerol and a decline of the phosphogalactolipids. The same changes are observed after inhibition of cell wall synthesis by various antibiotics, but not after inhibition of protein synthesis.", "contents": "Biochemical changes in Bifidobacterium bifidum var. pennsylvanicus after cell wall inhibition. VIII. Composition and metabolism of phospholipids at different stages and conditions of growth. 1. The phospholipid content and composition of Bifidobacterium bifidum var. pennsylvanicus is markedly influenced by the growth phase, the pH and the presence of human milk in the culture medium. 2. The lipid-phosphorus content of the cells increases during the first period of active growth, but decreases later. The lipid-phosphorus content of the cells in the stationary phase is at constant pH 5.5 about 45 percent of that at constant pH 6.8 and final pH 5.2. This difference is caused by a general reduction of all types of phospholipids. 3. Phosphatidylglycerol content decreases during growth, diphosphatidylglycerol increases in the first period, but decreases later and especially in the stationary phase by an increase of its lysoderivatives. The phosphogalactolipids rise during growth in the non-controlled pH-culture to 70 percent of the phospholipids in the stationary phase. When pH is constant at 6.8 and 5.5 glycerolphosphorylgalactosyldiglyceride remains at a constant level of about 20 percent during growth. At pH 6.8 glycerophosphorylmonogalactosylmonoglyceride increases to 24 percent during cultivation; at pH 5.5 this lipid contributes only a few percent. 4. Under all pH conditions, lack of human milk in the culture medium causes a marked increase of the lipid-phosphorus content of the cell, together with a high increase of the relative amounts of diphosphatidylglycerol and phosphatidylglycerol and a decline of the phosphogalactolipids. The same changes are observed after inhibition of cell wall synthesis by various antibiotics, but not after inhibition of protein synthesis."}
{"id": "PMID:237546", "title": "Prevention of cold inactivation of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase by NADPH.", "content": "Solubilized 3-hydroxy-3-methylglutaryl coenzyme A reductase (EC 1.1.1.34) from rat liver microsomes has been reported to be reversibly inactivated by temperatures below 19 degrees C. Cold inactivation has now been found to be completely prevented by NADPH and by NADP+ at a concentration of 3 mM. NADPH, however, was more active than NADP+ at lower concentrations and prevented 50% of the cold inactivation at 0.2 mM, whereas a 1.1 mM NADPH+ without effect and the substrate 3-hydroxy-3-methylglutaryl coenzyme A prevented only 30% of the cold inactivation at a concentration 50 times greater than the Km value.", "contents": "Prevention of cold inactivation of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase by NADPH. Solubilized 3-hydroxy-3-methylglutaryl coenzyme A reductase (EC 1.1.1.34) from rat liver microsomes has been reported to be reversibly inactivated by temperatures below 19 degrees C. Cold inactivation has now been found to be completely prevented by NADPH and by NADP+ at a concentration of 3 mM. NADPH, however, was more active than NADP+ at lower concentrations and prevented 50% of the cold inactivation at 0.2 mM, whereas a 1.1 mM NADPH+ without effect and the substrate 3-hydroxy-3-methylglutaryl coenzyme A prevented only 30% of the cold inactivation at a concentration 50 times greater than the Km value."}
{"id": "PMID:237547", "title": "The permeation of organic acids through lecithin bilayers. Resemblance to diffusion in polymers.", "content": "1. The fluxes of aliphatic acids and their derivatives through black lipid membranes made of egg lecithin in decane were measured by means of a proton titration method. 2. Permeability coefficients were calculated and these were divided by the partition coefficient of the diffusing solute in different solvent systems: n-decane, olive oil, ether and octanol. The logarithms of the diffusion coefficients thus obtained were plotted against the logarithm of the molecular weight. The data could not be fitted to a single regression line in any solvent system. 3. When the logarithm of the diffusion coefficients were correlated to the logarithm of the molecular volume (equals molecular weight/ specific gravity) all the diffusants could be fitted to the same regression line, indicating that the molecular volume is a better index of molecular size and shape than the molecular weight. 4. Analysis of the experimental results assuming a model of diffusion through soft polymers (Lieb, W.R. and Stein, W. D. (1971) Current Topics in Membranes and Transport, vol. 2, pp. 1-39, Academic Press, New York) showed that decane and olive oil are not adequate model solvents for planar lecithin membranes but ether and octanol are good models. 5. The differential mass selectivity coefficient was found to be similar to that for soft polymers and biological membranes, i.e. greater than 3.0. 6. Water could be fitted by the same regression line, thus emphasizing the generality of passive transfer and implying that water crosses lipid membranes as single molecules.", "contents": "The permeation of organic acids through lecithin bilayers. Resemblance to diffusion in polymers. 1. The fluxes of aliphatic acids and their derivatives through black lipid membranes made of egg lecithin in decane were measured by means of a proton titration method. 2. Permeability coefficients were calculated and these were divided by the partition coefficient of the diffusing solute in different solvent systems: n-decane, olive oil, ether and octanol. The logarithms of the diffusion coefficients thus obtained were plotted against the logarithm of the molecular weight. The data could not be fitted to a single regression line in any solvent system. 3. When the logarithm of the diffusion coefficients were correlated to the logarithm of the molecular volume (equals molecular weight/ specific gravity) all the diffusants could be fitted to the same regression line, indicating that the molecular volume is a better index of molecular size and shape than the molecular weight. 4. Analysis of the experimental results assuming a model of diffusion through soft polymers (Lieb, W.R. and Stein, W. D. (1971) Current Topics in Membranes and Transport, vol. 2, pp. 1-39, Academic Press, New York) showed that decane and olive oil are not adequate model solvents for planar lecithin membranes but ether and octanol are good models. 5. The differential mass selectivity coefficient was found to be similar to that for soft polymers and biological membranes, i.e. greater than 3.0. 6. Water could be fitted by the same regression line, thus emphasizing the generality of passive transfer and implying that water crosses lipid membranes as single molecules."}
{"id": "PMID:237548", "title": "The nature of the attachment of a regularly arranged surface protein to the outer membrane of an Acinetobacter sp.", "content": "Acinetobacter 199A carries on the outer surface of its outer membrane a layer of regularly arranged protein subunits. The isolated surface protein assembles into the same regular array even in the absence of the underlying outer membrane. Cl- minus is required for this self-assembly. Evidence is presented that the interaction of the surface protein with the outer membrane involves the linking of a carboxyl group in the surface protein to a negatively charged group in the outer membrane protein, via a divalent cation. The surface protein could be detached from the outer membrane by the protein perturbant urea, by the chelating agent EDTA and by replacing Mg-2+ with Na+. It could not be detached by treatment with phospholipases A anc D or the detergents Tween 80 and sodium deoxycholate. The conditions favourable for reattachment of surface protein to the cell wall were the presence of divalent cations and a pH of 3-5. Conversion of carboxyl groups in the surface protein to amine with carbodiimide and ethylene diamine interfered with reattachment. The surface protein did not attach to isolated cell wall lipid or lipopolysaccharide.", "contents": "The nature of the attachment of a regularly arranged surface protein to the outer membrane of an Acinetobacter sp. Acinetobacter 199A carries on the outer surface of its outer membrane a layer of regularly arranged protein subunits. The isolated surface protein assembles into the same regular array even in the absence of the underlying outer membrane. Cl- minus is required for this self-assembly. Evidence is presented that the interaction of the surface protein with the outer membrane involves the linking of a carboxyl group in the surface protein to a negatively charged group in the outer membrane protein, via a divalent cation. The surface protein could be detached from the outer membrane by the protein perturbant urea, by the chelating agent EDTA and by replacing Mg-2+ with Na+. It could not be detached by treatment with phospholipases A anc D or the detergents Tween 80 and sodium deoxycholate. The conditions favourable for reattachment of surface protein to the cell wall were the presence of divalent cations and a pH of 3-5. Conversion of carboxyl groups in the surface protein to amine with carbodiimide and ethylene diamine interfered with reattachment. The surface protein did not attach to isolated cell wall lipid or lipopolysaccharide."}
{"id": "PMID:237549", "title": "Proteolytic activity associated with human erythrocyte membranes. Self-digestion of isolated human erythrocyte membranes.", "content": "At least two kinds of enzymes are active in the proteolytic self-digestion of erythrocyte membranes. The specific activities of these enzymes do not decrease with repeated washings of purified stroma. The effects of a variety of inhibitors on the membrane preparation's capacity to digest 125-I-labelled casein, covalently linked to latex beads, have been examined. Pepstatin-inhibitable enzyme, active at low pH, digests the membrane extensively to small polypeptide fragments. Spectrin, located at the internal part of the membrane, is readily degraded. Diisopropylfluorophosphate-inhibitable enzyme, active at pH 8-9, has only limited digestive capacity. Some of the membrane components, such as the small molecular weight glycoproteins, are resistant to digestion. The restricted capacity of digestion is due to the membrane molecular arrangement; increased disaggregation removes the restriction and increases the activity. Spectrin is not digested unless the membrane topography is disrupted by NP-40 neutral detergent. These observations suggest that the enzymes active at basic pH are located external to the cell. Intact cells do possess a limited capacity to degrade 125-I-labelled casein when their surfaces are brought into contact with substrate-coated beads.", "contents": "Proteolytic activity associated with human erythrocyte membranes. Self-digestion of isolated human erythrocyte membranes. At least two kinds of enzymes are active in the proteolytic self-digestion of erythrocyte membranes. The specific activities of these enzymes do not decrease with repeated washings of purified stroma. The effects of a variety of inhibitors on the membrane preparation's capacity to digest 125-I-labelled casein, covalently linked to latex beads, have been examined. Pepstatin-inhibitable enzyme, active at low pH, digests the membrane extensively to small polypeptide fragments. Spectrin, located at the internal part of the membrane, is readily degraded. Diisopropylfluorophosphate-inhibitable enzyme, active at pH 8-9, has only limited digestive capacity. Some of the membrane components, such as the small molecular weight glycoproteins, are resistant to digestion. The restricted capacity of digestion is due to the membrane molecular arrangement; increased disaggregation removes the restriction and increases the activity. Spectrin is not digested unless the membrane topography is disrupted by NP-40 neutral detergent. These observations suggest that the enzymes active at basic pH are located external to the cell. Intact cells do possess a limited capacity to degrade 125-I-labelled casein when their surfaces are brought into contact with substrate-coated beads."}
{"id": "PMID:237550", "title": "[Gamma-glutamyltransferase activity in the human red blood cell membrane (author's transl)].", "content": "A gamma-glutamyltransferase activity is found in the human red blood cell membrane. Membrane isolation was carried out according to the method of Dodge et al. (Dodge, J. T., Mitchell, C. and Hanahan, J. (1963) Arch. Biochem. Biophys. 100, 119-130) (modified) and proteins were solubilized either with 1% sodium deoxycholate or 5 mM EDTA or 10 mM of its disodium salt, under various conditions of time and temperature. The gamma-glutamyltransferase activity of the membrane preparations was investigated using two substrates, gamma-L-glutamyl-p-nitroanilide and gamma-L-glutamyl-alpha-naphthylamide. The specific enzymatic activities of the various preparations, expressed in m units per mg of protein, were found to have similar values under similar technical conditions. The chelating agents seem to allow a more specific isolation than the detergent. The presence of a gamma-glutamyltransferase activity in the erythrocyte membrane is discussed in relation to the membrane association of this enzyme in other tissues.", "contents": "[Gamma-glutamyltransferase activity in the human red blood cell membrane (author's transl)]. A gamma-glutamyltransferase activity is found in the human red blood cell membrane. Membrane isolation was carried out according to the method of Dodge et al. (Dodge, J. T., Mitchell, C. and Hanahan, J. (1963) Arch. Biochem. Biophys. 100, 119-130) (modified) and proteins were solubilized either with 1% sodium deoxycholate or 5 mM EDTA or 10 mM of its disodium salt, under various conditions of time and temperature. The gamma-glutamyltransferase activity of the membrane preparations was investigated using two substrates, gamma-L-glutamyl-p-nitroanilide and gamma-L-glutamyl-alpha-naphthylamide. The specific enzymatic activities of the various preparations, expressed in m units per mg of protein, were found to have similar values under similar technical conditions. The chelating agents seem to allow a more specific isolation than the detergent. The presence of a gamma-glutamyltransferase activity in the erythrocyte membrane is discussed in relation to the membrane association of this enzyme in other tissues."}
{"id": "PMID:237551", "title": "Hydrolytic and transglucosylation activities of a purified calf spleen beta-glucosidase.", "content": "Certain properties of the transglucosylitic activity and the hydrolytic activity of a purified calf spleen beta-glucosidase (beta-D-glucoside glucohydrolase EC 3.2.1.21) were investigated. There was a stimulation of both activities by sodium taurocholate and \"Gaucher's factor\". The K-m values for 4-methylumbelliferyl-beta-D-glucoside and glucosylceramide as donors in the transglucosylation reaction were 2 mM and 0.075 mM, respectively. The K-m for ceramide as acceptor was 0.149 mM with both of these compounds. The ability of several glucoside to act as donors was examined. The capacity to catalyze this \"transglucosylation\" reaction is greatly diminished in spleen tissue samples from Gaucher's patients. The enzyme possesses the capacity to hyrolyze 4-methylumbellifery-beta-D-glucoside, p-nitrophenyl-beta-D-glucoside, glucosylsphingosine, glucosylceramide and deoxycorticosterol-beta-D-glucoside. It is postulated that a single enzyme protein may be responsible for both the hydrolytic and the transglucosylitic activities.", "contents": "Hydrolytic and transglucosylation activities of a purified calf spleen beta-glucosidase. Certain properties of the transglucosylitic activity and the hydrolytic activity of a purified calf spleen beta-glucosidase (beta-D-glucoside glucohydrolase EC 3.2.1.21) were investigated. There was a stimulation of both activities by sodium taurocholate and \"Gaucher's factor\". The K-m values for 4-methylumbelliferyl-beta-D-glucoside and glucosylceramide as donors in the transglucosylation reaction were 2 mM and 0.075 mM, respectively. The K-m for ceramide as acceptor was 0.149 mM with both of these compounds. The ability of several glucoside to act as donors was examined. The capacity to catalyze this \"transglucosylation\" reaction is greatly diminished in spleen tissue samples from Gaucher's patients. The enzyme possesses the capacity to hyrolyze 4-methylumbellifery-beta-D-glucoside, p-nitrophenyl-beta-D-glucoside, glucosylsphingosine, glucosylceramide and deoxycorticosterol-beta-D-glucoside. It is postulated that a single enzyme protein may be responsible for both the hydrolytic and the transglucosylitic activities."}
{"id": "PMID:237552", "title": "Purification of G-M-1-ganglioside and ceramide lactoside beta-galactosidase from rabbit brain.", "content": "The major beta-galactosidase of rabbit brain has been purified over 400-fold. The enzyme converts G-M-1-ganglioside; Gal beta-1 yields 3 GalNAc beta-1 yields 4 (NANalpha-2 yields 3) Gal beta-1 yields 4 Glc yields ceramide (G-M-1) into Tay Sachs ganglioside GalNAc beta-1 yields 4 (NANalpha-2 yields 3) Gal beta-1 yields 4 Glc yields ceramide (G-M-2-ganglioside) and ceramide lactoside, Gal beta-1 yields 4 Glc yields ceramide (Gal-Glc-Cer) into glucocerebroside, Glc yields ceramide (Glc-Cer). The enzyme also hydrolyzes the synthetic substrates NPh-Gal and MeUmb-Gal. It is eluted as a single peak from Sephadex G-200 columns when natural and synthetic substrates were used and has an isoelectric point of 6.3. We were unable to resolve activity towards G-M-1-ganglioside and Gal-Glc-Cer by polyacrylamide electrophoresis in two buffer systems. With G-M-1 the pH optimum was 4.3 in acetate buffer and the K-m value 78 mu-M while with Gal-Glc-Cer, a pH optimum of 4.5 and a K-m of 17 mu-M were found. Hydrolysis of both natural and synthetic substrates was inhibited by gamma-D-galactonolactone, D-galactose and lactose. The data strongly suggest that a single beta-galactosidase hydrolyzes all the substrates tested.", "contents": "Purification of G-M-1-ganglioside and ceramide lactoside beta-galactosidase from rabbit brain. The major beta-galactosidase of rabbit brain has been purified over 400-fold. The enzyme converts G-M-1-ganglioside; Gal beta-1 yields 3 GalNAc beta-1 yields 4 (NANalpha-2 yields 3) Gal beta-1 yields 4 Glc yields ceramide (G-M-1) into Tay Sachs ganglioside GalNAc beta-1 yields 4 (NANalpha-2 yields 3) Gal beta-1 yields 4 Glc yields ceramide (G-M-2-ganglioside) and ceramide lactoside, Gal beta-1 yields 4 Glc yields ceramide (Gal-Glc-Cer) into glucocerebroside, Glc yields ceramide (Glc-Cer). The enzyme also hydrolyzes the synthetic substrates NPh-Gal and MeUmb-Gal. It is eluted as a single peak from Sephadex G-200 columns when natural and synthetic substrates were used and has an isoelectric point of 6.3. We were unable to resolve activity towards G-M-1-ganglioside and Gal-Glc-Cer by polyacrylamide electrophoresis in two buffer systems. With G-M-1 the pH optimum was 4.3 in acetate buffer and the K-m value 78 mu-M while with Gal-Glc-Cer, a pH optimum of 4.5 and a K-m of 17 mu-M were found. Hydrolysis of both natural and synthetic substrates was inhibited by gamma-D-galactonolactone, D-galactose and lactose. The data strongly suggest that a single beta-galactosidase hydrolyzes all the substrates tested."}
{"id": "PMID:237554", "title": "Hexosaminidase C in Tay-Sachs and Sandhoff disease.", "content": "1. Hexosaminidase C has been purified from human placenta. Complete separation from hexosaminidases A and B was achieved. 2. The following properties of hexosaminidase C differ from those of the A and B isozymes. Presence in the supernatant rather than the lysosomes, neutral pH optimum, higher molecular weight, lack of activity on beta-N-acetylgalactosamine derivatives, and lack of immunological relationship. 3. Hexosaminidase C is active in patients deficient in hexosaminidases A and B and can be recognized by its characteristic electrophoretic mobility. It is concluded that the genetic origin of hexosaminidase C is probably different from that of hexosaminidases A and B.", "contents": "Hexosaminidase C in Tay-Sachs and Sandhoff disease. 1. Hexosaminidase C has been purified from human placenta. Complete separation from hexosaminidases A and B was achieved. 2. The following properties of hexosaminidase C differ from those of the A and B isozymes. Presence in the supernatant rather than the lysosomes, neutral pH optimum, higher molecular weight, lack of activity on beta-N-acetylgalactosamine derivatives, and lack of immunological relationship. 3. Hexosaminidase C is active in patients deficient in hexosaminidases A and B and can be recognized by its characteristic electrophoretic mobility. It is concluded that the genetic origin of hexosaminidase C is probably different from that of hexosaminidases A and B."}
{"id": "PMID:237555", "title": "Studies on the kinetics of glycosidases from chemically-induced rat colonic tumours and normal rat colon.", "content": "K-m values of beta-N-acetylglucosaminidase (2-acetamido-2-deoxy-beta-D-glucoside acetamidodeoxyglucohydrolase EC 3.2.1.30), beta-N-acetylgalactosaminidase (EC 3.2.1.53), beta-galactosidase (beta-D-galactoside galactohydrolase EC 3.2.1.23) and alpha-L-fucosidase (alpha-L-fucoside fucohydrolase EC 3.2.1.51) of distal colonic tumours, induced in rats by 1,2-dimethylhydrazine, were found to be significantly different compared with the values for the enzymes of the colonic mucosa of the control and tumour-bearing animals and of the proximal colonic tumours. The inhibition kinetics data also showed a significant difference between the enzymes of the distal colon tumours and of other experimental tissues. The data on the effect of pH on enzyme kinetics (pK values) showed no significant difference in the catalytic groups of the active centres of enzymes from tumours and from the control colonic mucosa. Tumour beta-N-acetylglucosaminidase and beta-N-acetylgalactosaminidase compared with the enzymes from other experimental tissues were found to be different in their thermal inactivation kinetics. K-m values of 14 days old foetal intestinal beta-N-acetylglucosaminidase and beta-N-acetylgalactosaminidase were significantly different from the values obtained for the adult mucosal enzymes but were similar to those of the distal colonic tumour enzymes.", "contents": "Studies on the kinetics of glycosidases from chemically-induced rat colonic tumours and normal rat colon. K-m values of beta-N-acetylglucosaminidase (2-acetamido-2-deoxy-beta-D-glucoside acetamidodeoxyglucohydrolase EC 3.2.1.30), beta-N-acetylgalactosaminidase (EC 3.2.1.53), beta-galactosidase (beta-D-galactoside galactohydrolase EC 3.2.1.23) and alpha-L-fucosidase (alpha-L-fucoside fucohydrolase EC 3.2.1.51) of distal colonic tumours, induced in rats by 1,2-dimethylhydrazine, were found to be significantly different compared with the values for the enzymes of the colonic mucosa of the control and tumour-bearing animals and of the proximal colonic tumours. The inhibition kinetics data also showed a significant difference between the enzymes of the distal colon tumours and of other experimental tissues. The data on the effect of pH on enzyme kinetics (pK values) showed no significant difference in the catalytic groups of the active centres of enzymes from tumours and from the control colonic mucosa. Tumour beta-N-acetylglucosaminidase and beta-N-acetylgalactosaminidase compared with the enzymes from other experimental tissues were found to be different in their thermal inactivation kinetics. K-m values of 14 days old foetal intestinal beta-N-acetylglucosaminidase and beta-N-acetylgalactosaminidase were significantly different from the values obtained for the adult mucosal enzymes but were similar to those of the distal colonic tumour enzymes."}
{"id": "PMID:237556", "title": "Properties and specificity of the major anionic trypsin-like enzyme in the keratinolytic larvae of the webbing clothes moth.", "content": "The major form of the trypsin-like proteinases from the larvae of the webbing clothes moth Tineola bisselliella has been further purified and some of its properties investigated. It differs from bovine trypsin in several respects. It is anionic at neutral pH, is very stable at alkaline pH, has no requirement for calcium ions for this stability and is very sensitive to urea. It resembles vertebrate trypsins in its complete inhibition by diisopropylfluorophosphate, its pH optimum of 8.5 for hydrolysis of benzoyl-arginine p-nitroanilide and its cleavage specificity against glucagon and the beta-chain of S-carboxymethyl insulin.", "contents": "Properties and specificity of the major anionic trypsin-like enzyme in the keratinolytic larvae of the webbing clothes moth. The major form of the trypsin-like proteinases from the larvae of the webbing clothes moth Tineola bisselliella has been further purified and some of its properties investigated. It differs from bovine trypsin in several respects. It is anionic at neutral pH, is very stable at alkaline pH, has no requirement for calcium ions for this stability and is very sensitive to urea. It resembles vertebrate trypsins in its complete inhibition by diisopropylfluorophosphate, its pH optimum of 8.5 for hydrolysis of benzoyl-arginine p-nitroanilide and its cleavage specificity against glucagon and the beta-chain of S-carboxymethyl insulin."}
{"id": "PMID:237557", "title": "Allantoin racemase: a new enzyme from Pseudomonas species.", "content": "1. Allantoin racemase is a novel enzyme which catalyzes the conversion of S(+)-and R(minus)-allantoin into the racemate. 2. The enzyme is present in Pseudomonas testosteroni, Pseudomonas putida and five biotypes of Pseudomonas fluorescens, but absent in a number of other Pseudomonas species. 3. The enzyme of Ps. testosteroni was purified 133-fold and exposes optimal activity at pH 8.0-8.2 and 50 degrees C. The enzyme is stable on heating for 15 min at 70 degrees C. 4. The enzyme appeared to be specific for the optical isomers of allantoin and no cofactors are involved in the reaction. 5. The optical aspecificity of allantoinase of Proteus rettgeri was reaffirmed.", "contents": "Allantoin racemase: a new enzyme from Pseudomonas species. 1. Allantoin racemase is a novel enzyme which catalyzes the conversion of S(+)-and R(minus)-allantoin into the racemate. 2. The enzyme is present in Pseudomonas testosteroni, Pseudomonas putida and five biotypes of Pseudomonas fluorescens, but absent in a number of other Pseudomonas species. 3. The enzyme of Ps. testosteroni was purified 133-fold and exposes optimal activity at pH 8.0-8.2 and 50 degrees C. The enzyme is stable on heating for 15 min at 70 degrees C. 4. The enzyme appeared to be specific for the optical isomers of allantoin and no cofactors are involved in the reaction. 5. The optical aspecificity of allantoinase of Proteus rettgeri was reaffirmed."}
{"id": "PMID:237558", "title": "Studies on matrix vesicles isolated from chick epiphyseal cartilage. Association of pyrophosphatase and ATPase activities with alkaline phosphatase.", "content": "Fractions composed primarily of cells (Fraction I), membrane fragments (Fraction II) and matrix vesicles (Fraction III) were isolated from chick epiphyseal cartilage. The characteristics of the alkaline phosphatase (EC 3.1.3.1), pyrophosphatase (EC 3.6.1.1) and ATPase (EC 3.6.1.3) activities in the matrix vesicle fraction were studied in detail. Mg-2-+ was not absolutely essential to any of the activities, but at low levels was stimulatory in all cases. Higher concentrations inhibited both pyrophosphatase and ATPase activities. Both the stimulatory and inhibitory effects were pH-dependent. Ca-2-+ stimulated all activities weakly in the absence of Mg-2-+. However, when Mg-2-+ was present, Ca-2-+ was slightly inhibitory. Thus, none of the activities appear to have a requirement for Ca-2-+, and hence would not seem to be involved with active Ca-2-+ transport in the typical manner. The distribution of alkaline phosphatase, pyrophosphatase, and Mg-2-+ ATPase activities among the various cartilage fractions was identical, and concentrated primarily in the matrix vesicles. Conversely, the highest level of (Na-+ + K-+)-ATPase activity was found in the cell fraction. All activites showed nearly identical sensitivities to levamisole (4 - 10-3 M) which caused nearly complete inhibition of alkaline phosphatase and pyrophosphatase. About 10-15% of the ATPase activity was levamisole-insensitive. The data are consistent with the concept that the Mg-2-+-ATPase and pyrophosphatase activities of matrix vesicles stem from one enzyme, namely, alkaline phosphatase.", "contents": "Studies on matrix vesicles isolated from chick epiphyseal cartilage. Association of pyrophosphatase and ATPase activities with alkaline phosphatase. Fractions composed primarily of cells (Fraction I), membrane fragments (Fraction II) and matrix vesicles (Fraction III) were isolated from chick epiphyseal cartilage. The characteristics of the alkaline phosphatase (EC 3.1.3.1), pyrophosphatase (EC 3.6.1.1) and ATPase (EC 3.6.1.3) activities in the matrix vesicle fraction were studied in detail. Mg-2-+ was not absolutely essential to any of the activities, but at low levels was stimulatory in all cases. Higher concentrations inhibited both pyrophosphatase and ATPase activities. Both the stimulatory and inhibitory effects were pH-dependent. Ca-2-+ stimulated all activities weakly in the absence of Mg-2-+. However, when Mg-2-+ was present, Ca-2-+ was slightly inhibitory. Thus, none of the activities appear to have a requirement for Ca-2-+, and hence would not seem to be involved with active Ca-2-+ transport in the typical manner. The distribution of alkaline phosphatase, pyrophosphatase, and Mg-2-+ ATPase activities among the various cartilage fractions was identical, and concentrated primarily in the matrix vesicles. Conversely, the highest level of (Na-+ + K-+)-ATPase activity was found in the cell fraction. All activites showed nearly identical sensitivities to levamisole (4 - 10-3 M) which caused nearly complete inhibition of alkaline phosphatase and pyrophosphatase. About 10-15% of the ATPase activity was levamisole-insensitive. The data are consistent with the concept that the Mg-2-+-ATPase and pyrophosphatase activities of matrix vesicles stem from one enzyme, namely, alkaline phosphatase."}
{"id": "PMID:237559", "title": "Acid phosphatase and adenosine triphosphatase activities in the cell wall of baker's yeast.", "content": "In order to establish whether a specific adenosine triphosphatase is present in yeast cell wall, hydrolysis rates for p-nitrophenylphosphate (acid phosphatase activity) and for ATP (ATPase activity) were compared under various conditions. Rate determinations were made with both, intact cells and with preparations containing secreted enzymes from protoplasts. Acid phosphatase and ATPase activities had the same pH profile and were susceptible in the same way to the repression by orthophosphate and to the inhibition by 2-deoxyglucose. The Lineweaver-Burk plot shows biphasic kinetic behaviour for the hydrolysis of either p-nitrophenylphosphate or ATP. This suggests the existence of two enzymes with different affinities for the substrates, or one enzyme with at least two active sites. The two activities differ in thermostability and only one activity could be completely abolished by heat treatment. The thermostable enzyme activity had K-m values of 0.475 mM for p-nitrophenylphosphate, and 0.040 mM for ATP. ATP behaved as a partially competitive inhibitor of p-nitrophenylphosphate hydrolysis. Substrate competition studies showed that only a non-specific acid phosphatase is responsible for the hydrolysis of ATP.", "contents": "Acid phosphatase and adenosine triphosphatase activities in the cell wall of baker's yeast. In order to establish whether a specific adenosine triphosphatase is present in yeast cell wall, hydrolysis rates for p-nitrophenylphosphate (acid phosphatase activity) and for ATP (ATPase activity) were compared under various conditions. Rate determinations were made with both, intact cells and with preparations containing secreted enzymes from protoplasts. Acid phosphatase and ATPase activities had the same pH profile and were susceptible in the same way to the repression by orthophosphate and to the inhibition by 2-deoxyglucose. The Lineweaver-Burk plot shows biphasic kinetic behaviour for the hydrolysis of either p-nitrophenylphosphate or ATP. This suggests the existence of two enzymes with different affinities for the substrates, or one enzyme with at least two active sites. The two activities differ in thermostability and only one activity could be completely abolished by heat treatment. The thermostable enzyme activity had K-m values of 0.475 mM for p-nitrophenylphosphate, and 0.040 mM for ATP. ATP behaved as a partially competitive inhibitor of p-nitrophenylphosphate hydrolysis. Substrate competition studies showed that only a non-specific acid phosphatase is responsible for the hydrolysis of ATP."}
{"id": "PMID:237560", "title": "Cyclic nucleotide phosphodiesterase in silkworm. Separation and characterization of multiple forms of the enzyme.", "content": "The existence of two forms of cyclic AMP phosphodiesterase (3',5'-cyclic AMP 5'-nucleotidohydrolase, EC 3.1.4.17) was demonstrated in silkworm larvae by kinetic analysis and DEAE-cellulose column chromatography. The two forms of the enzyme (phosphodiesterase II and III) differ apparently in their characteristics from the previously reported cyclic nucleotide phosphodiesterase (phosphodiesterase I) of silkworm. The higher K-m form (phosphodiesterase II) has a molecular weight of approx. 50 000 and optimum pH of 7.8, and requires Mn-2-+ for maximum activity. The lower K-m form (phosphodiesterase III) has a molecular weight of approx. 97 000 and optimum pH of 7.2, and requires Mg-2-+ for maximum activity. Phosphodiesterase II and probably phosphodiesterase III are specific enzymes for the hydrolysis of cyclic AMP.", "contents": "Cyclic nucleotide phosphodiesterase in silkworm. Separation and characterization of multiple forms of the enzyme. The existence of two forms of cyclic AMP phosphodiesterase (3',5'-cyclic AMP 5'-nucleotidohydrolase, EC 3.1.4.17) was demonstrated in silkworm larvae by kinetic analysis and DEAE-cellulose column chromatography. The two forms of the enzyme (phosphodiesterase II and III) differ apparently in their characteristics from the previously reported cyclic nucleotide phosphodiesterase (phosphodiesterase I) of silkworm. The higher K-m form (phosphodiesterase II) has a molecular weight of approx. 50 000 and optimum pH of 7.8, and requires Mn-2-+ for maximum activity. The lower K-m form (phosphodiesterase III) has a molecular weight of approx. 97 000 and optimum pH of 7.2, and requires Mg-2-+ for maximum activity. Phosphodiesterase II and probably phosphodiesterase III are specific enzymes for the hydrolysis of cyclic AMP."}
{"id": "PMID:237561", "title": "Purification of an alkaline ribonuclease from soluble fraction of beef brain.", "content": "A ribonuclease (ribonucleate 3-pyrimidine-oligonucleotidohydrolase, EC 3.1.4.22) was purified 8300-fold from soluble fraction of beef brain and its properties were investigated. The enzyme is an endonuclease capable of hydrolyzing tRNA, rRNA, poly(C), but shows no activity towards poly(U), poly(A), and poly(G). The preparation is free of deoxyribonuclease, non-specific phosphodiesterase and phosphomonoesterase activity. The enzyme has a pH optimum of 7.6, is not heat stable, has a molecular weight of 25 000, and has a K-m of 134 mu rRNA and K-m of 1600 mug poly(C) per ml.", "contents": "Purification of an alkaline ribonuclease from soluble fraction of beef brain. A ribonuclease (ribonucleate 3-pyrimidine-oligonucleotidohydrolase, EC 3.1.4.22) was purified 8300-fold from soluble fraction of beef brain and its properties were investigated. The enzyme is an endonuclease capable of hydrolyzing tRNA, rRNA, poly(C), but shows no activity towards poly(U), poly(A), and poly(G). The preparation is free of deoxyribonuclease, non-specific phosphodiesterase and phosphomonoesterase activity. The enzyme has a pH optimum of 7.6, is not heat stable, has a molecular weight of 25 000, and has a K-m of 134 mu rRNA and K-m of 1600 mug poly(C) per ml."}
{"id": "PMID:237562", "title": "A Pseudomonas intracellular amylase with high activity on maltodextrins and cyclodextrins.", "content": "An intracellular amylase from Pseudomonas MSl was purified 95-fold in a 14% yield by fractionation with (NH4) 2SO4, followed by chromatographies on CM-cellulose, hydroxylapatite and Sephadex G-200. On polyacrylamide gel electrophoresis at pH 8.3 it gave a single band and its molecular weight was determined to be 96 000 from its mobility on sodium dodecylsulfate gel electrophoresis. Its activity was maximal at pH 5.5 and 50 degrees C. This enzyme hydrolyzed maltotriose and maltotetraose faster than amylose, but did not hydrolyze maltose. It also rapidly hydrolyzed a series of cyclomaltodextrins. Amylopectin and glycogen, which have branched structures, were attacked much slower than amylose. The enzyme cleaved the substrates in an endo-wise fashion and produced almost equimolar amounts of glucose and maltose as the final products from various substrates. The enzyme mechanism is discussed on the basis of quantitative autoradiographic data. The K-m values for maltotriose, maltotetraose, cyclomaltohexaose, corn amylose and waxycorn amylopectin were 1.0, 1.4, 3.5, 3.3 and 13 - 10-minus 3 g/ml, respectively. The products of the enzyme had an alpha-configuration. Thus, this enzyme is a specific alpha-amylase.", "contents": "A Pseudomonas intracellular amylase with high activity on maltodextrins and cyclodextrins. An intracellular amylase from Pseudomonas MSl was purified 95-fold in a 14% yield by fractionation with (NH4) 2SO4, followed by chromatographies on CM-cellulose, hydroxylapatite and Sephadex G-200. On polyacrylamide gel electrophoresis at pH 8.3 it gave a single band and its molecular weight was determined to be 96 000 from its mobility on sodium dodecylsulfate gel electrophoresis. Its activity was maximal at pH 5.5 and 50 degrees C. This enzyme hydrolyzed maltotriose and maltotetraose faster than amylose, but did not hydrolyze maltose. It also rapidly hydrolyzed a series of cyclomaltodextrins. Amylopectin and glycogen, which have branched structures, were attacked much slower than amylose. The enzyme cleaved the substrates in an endo-wise fashion and produced almost equimolar amounts of glucose and maltose as the final products from various substrates. The enzyme mechanism is discussed on the basis of quantitative autoradiographic data. The K-m values for maltotriose, maltotetraose, cyclomaltohexaose, corn amylose and waxycorn amylopectin were 1.0, 1.4, 3.5, 3.3 and 13 - 10-minus 3 g/ml, respectively. The products of the enzyme had an alpha-configuration. Thus, this enzyme is a specific alpha-amylase."}
{"id": "PMID:237563", "title": "The molecular weight of bovine lactoferrin.", "content": "The molecular weight of bovine lactoferrin in a neutral solvent (e.g. 0.2 M NaC1, pH 7.8 20 degrees C) has been determined using high-speed sedimentation equilibrium at various concentrations and speeds. Under these conditions the protein behaved as a single thermodynamic component with a weight-average molecular weight [MW]C=0 = 93000 plus or minus 2000 and a second virial coefficient B = 4.3-10(-5) mol-ml(-1)-g(-2). This value of the molecular weight is in good agreement with values previously reported by Groves (J. Am. Chem. Soc. 82, 3345-3350, 1960) and Szuchet and Johnson (Eur. Polym. J. 2, 115-128, 1966); it is, however, in disagreement with the more recent value given by Castellino et al. (J. Biol. Chem. 245, 4269-4275, 1970). The possible reasons for this discrepancy are discussed.", "contents": "The molecular weight of bovine lactoferrin. The molecular weight of bovine lactoferrin in a neutral solvent (e.g. 0.2 M NaC1, pH 7.8 20 degrees C) has been determined using high-speed sedimentation equilibrium at various concentrations and speeds. Under these conditions the protein behaved as a single thermodynamic component with a weight-average molecular weight [MW]C=0 = 93000 plus or minus 2000 and a second virial coefficient B = 4.3-10(-5) mol-ml(-1)-g(-2). This value of the molecular weight is in good agreement with values previously reported by Groves (J. Am. Chem. Soc. 82, 3345-3350, 1960) and Szuchet and Johnson (Eur. Polym. J. 2, 115-128, 1966); it is, however, in disagreement with the more recent value given by Castellino et al. (J. Biol. Chem. 245, 4269-4275, 1970). The possible reasons for this discrepancy are discussed."}
{"id": "PMID:237564", "title": "The application of QAE-Sephadex for the purification of two staphylococcal enterotoxins. I. Purification of enterotoxin C2.", "content": "A new method developed for purification of enterotoxin C2 from Staphylococcus aureus strain 361 consisted of four steps: batchwise adsorption from culture supernatant on QAE-Sephadex; gel filtration on Sephadex G-100; chromatography on QAE-Sephadex using a buffer of constant pH and molarity; and gel filtration using a volatile buffer of constant pH and molarity; and gel filtration using a volatile buffer as the eluting solvent. The purified enterotoxin appeared homogeneous by gel immunodiffusion, gel chromatography and in the analytical ultracentrifuge, although an apparent heterogeneity was noted on QAE-Sephadex chromatography and polyacrylamide disc electrophoresis at pH 4.5. The emetic dose, ED50, by intravenous route in cynomolgus monkeys was 0.04 mug/kg of animal weight. Upon treatment with sodium dodecylsulfate, beta-mercaptoethanol and urea, enterotoxin C2 separated into 3 bands in sodium dodecylsulfate-electrophoresis. One band mol. wt 29000, and two bands of lower molecular weight were so close that they moved as a single zone. After elution from gels, the zone of lower molecular weight were so close that they moved as a single zone. After elution from gels, the zone of lower molecular weight oligopeptides emerged as a single peak at the same position as untreated enterotoxin C2 during gel filtration with buffer lacking thiol and denaturant, and gave a reaction of complete identify to enterotoxin C2 in Ouchterlony immunodiffusion. The results suggest that enterotoxin C2 is a mixture composed of intact polypeptide chains, mol. wt 29000, and two fragments cleaved in the disulfide region of molecular weight of approx. 15400 and 12800 linked by the single disulfide bond in the toxin molecule. Amino acid analysis indicates that enterotoxin C2 consists of 255 amino acid residues.", "contents": "The application of QAE-Sephadex for the purification of two staphylococcal enterotoxins. I. Purification of enterotoxin C2. A new method developed for purification of enterotoxin C2 from Staphylococcus aureus strain 361 consisted of four steps: batchwise adsorption from culture supernatant on QAE-Sephadex; gel filtration on Sephadex G-100; chromatography on QAE-Sephadex using a buffer of constant pH and molarity; and gel filtration using a volatile buffer of constant pH and molarity; and gel filtration using a volatile buffer as the eluting solvent. The purified enterotoxin appeared homogeneous by gel immunodiffusion, gel chromatography and in the analytical ultracentrifuge, although an apparent heterogeneity was noted on QAE-Sephadex chromatography and polyacrylamide disc electrophoresis at pH 4.5. The emetic dose, ED50, by intravenous route in cynomolgus monkeys was 0.04 mug/kg of animal weight. Upon treatment with sodium dodecylsulfate, beta-mercaptoethanol and urea, enterotoxin C2 separated into 3 bands in sodium dodecylsulfate-electrophoresis. One band mol. wt 29000, and two bands of lower molecular weight were so close that they moved as a single zone. After elution from gels, the zone of lower molecular weight were so close that they moved as a single zone. After elution from gels, the zone of lower molecular weight oligopeptides emerged as a single peak at the same position as untreated enterotoxin C2 during gel filtration with buffer lacking thiol and denaturant, and gave a reaction of complete identify to enterotoxin C2 in Ouchterlony immunodiffusion. The results suggest that enterotoxin C2 is a mixture composed of intact polypeptide chains, mol. wt 29000, and two fragments cleaved in the disulfide region of molecular weight of approx. 15400 and 12800 linked by the single disulfide bond in the toxin molecule. Amino acid analysis indicates that enterotoxin C2 consists of 255 amino acid residues."}
{"id": "PMID:237565", "title": "Studies on phytohemagglutinins. XXIV. Isoelectric point and hybridization of the pea (Pisum sativum L.) isophytohemagglutinins.", "content": "The isoelectric point of the two pea isophytohemagglutinins varies from pH 5.7 to pH 8.4 depending on the composition of the buffer used. Isoelectric focusing reveals three main molecular species with pI at pH 5.90, 6.35 and 7.00. Molecular species with pI at pH 5.9 and 7.0 correspond to the two pea isophytohemagglutinins which can be obtained by DEAE-cellulose chromatography (Entlicher, G., Kost\u00edr, J.V. and Kocurek, J. (1970) Biochim. Biophys. Acta 221, 272-281). A molecular species with pI at pH 6.35 is formed from the two pea isophytohemagglutinins by hybridization. According to the hybridization pattern and subunit composition of the pea isophytohemagglutinins the subunit composition AABB, AACC and AABC can be proposed for the three molecular species with respect to ionic properties of the subunits.", "contents": "Studies on phytohemagglutinins. XXIV. Isoelectric point and hybridization of the pea (Pisum sativum L.) isophytohemagglutinins. The isoelectric point of the two pea isophytohemagglutinins varies from pH 5.7 to pH 8.4 depending on the composition of the buffer used. Isoelectric focusing reveals three main molecular species with pI at pH 5.90, 6.35 and 7.00. Molecular species with pI at pH 5.9 and 7.0 correspond to the two pea isophytohemagglutinins which can be obtained by DEAE-cellulose chromatography (Entlicher, G., Kost\u00edr, J.V. and Kocurek, J. (1970) Biochim. Biophys. Acta 221, 272-281). A molecular species with pI at pH 6.35 is formed from the two pea isophytohemagglutinins by hybridization. According to the hybridization pattern and subunit composition of the pea isophytohemagglutinins the subunit composition AABB, AACC and AABC can be proposed for the three molecular species with respect to ionic properties of the subunits."}
{"id": "PMID:237566", "title": "Haemoglobin Saki alpha 2 beta 2 14 Leu-Pro(a11) structure and function.", "content": "The characterization of haemoglobin Saki alpha 2 beta 2 14 Leu-Pro(a11) is described. This new mutation is unique since it only induces modification of the stability of the molecule. In vitro precipitation of haemoglobin Saki upon heat or in the presence of chemicals is compared to the stability of haemoglobin A and haemoglobin S.", "contents": "Haemoglobin Saki alpha 2 beta 2 14 Leu-Pro(a11) structure and function. The characterization of haemoglobin Saki alpha 2 beta 2 14 Leu-Pro(a11) is described. This new mutation is unique since it only induces modification of the stability of the molecule. In vitro precipitation of haemoglobin Saki upon heat or in the presence of chemicals is compared to the stability of haemoglobin A and haemoglobin S."}
{"id": "PMID:237567", "title": "Interaction between proteins and detergents which contain a hydrocarbon chain longer than 16 carbon atoms. II. Difference spectra of various proteins in cetyldimethyl-benzylammonium chloride.", "content": "The detergents which contain a hydrocarbon side chain longer than 16 cabron atoms were used as a perturbant for the study of protein structure. ta low concentration of cetyldimethylbenzylammonium chloride (CDBA) caused difference spectra for Ac-Trp-OEt and AC-Tyr-OEt. The delta e values at their difference maxima became constant above 30 mM of cetyldimethylbenzylammonium chloride, 1430 at 294 nm for Ac-Trp-OEt and 450 at 288 nm for Ac-Tyr-OEt. These delta e values are higher than any other delta e values resulting from solvent effects by such a remarkably low concentration of organic reagents described in the literature so far. The absence of denaturation blue shift in the difference spectra and the fact that the optical rotatory dispersion of the proteins examined in the present study was not changed significantly by cetyldimethylbenzylammonium chloride indicate that the secondary and tertiary structures of the proteins were not destroyed by cetyldimethylbenzylammonium chloride. These characteristics, together with small overlapping of their difference spectra at 288 and 294 nm were advantageous in the determination of tryptophan and tyrosine residues exposed in glucagon, insulin and alcohol dehydrogenase from yeast. No tyrosine residues in ribonuclease A was accessible to cetyldimethylbenzylammonium chloride. Unusual difference spectrum with a peak at 298 nm was observed for lysozyme which is known to contain tryptophan residues in special environments. Ovalbumin gave a novel unusual difference spectrum with a peak at 290 nm and a shoulder at 298 nm, showing the existence of unusual tryptophan and probably tyrosine residues in the molecule.", "contents": "Interaction between proteins and detergents which contain a hydrocarbon chain longer than 16 carbon atoms. II. Difference spectra of various proteins in cetyldimethyl-benzylammonium chloride. The detergents which contain a hydrocarbon side chain longer than 16 cabron atoms were used as a perturbant for the study of protein structure. ta low concentration of cetyldimethylbenzylammonium chloride (CDBA) caused difference spectra for Ac-Trp-OEt and AC-Tyr-OEt. The delta e values at their difference maxima became constant above 30 mM of cetyldimethylbenzylammonium chloride, 1430 at 294 nm for Ac-Trp-OEt and 450 at 288 nm for Ac-Tyr-OEt. These delta e values are higher than any other delta e values resulting from solvent effects by such a remarkably low concentration of organic reagents described in the literature so far. The absence of denaturation blue shift in the difference spectra and the fact that the optical rotatory dispersion of the proteins examined in the present study was not changed significantly by cetyldimethylbenzylammonium chloride indicate that the secondary and tertiary structures of the proteins were not destroyed by cetyldimethylbenzylammonium chloride. These characteristics, together with small overlapping of their difference spectra at 288 and 294 nm were advantageous in the determination of tryptophan and tyrosine residues exposed in glucagon, insulin and alcohol dehydrogenase from yeast. No tyrosine residues in ribonuclease A was accessible to cetyldimethylbenzylammonium chloride. Unusual difference spectrum with a peak at 298 nm was observed for lysozyme which is known to contain tryptophan residues in special environments. Ovalbumin gave a novel unusual difference spectrum with a peak at 290 nm and a shoulder at 298 nm, showing the existence of unusual tryptophan and probably tyrosine residues in the molecule."}
{"id": "PMID:237568", "title": "The effects of the trinitrophenylation of the amino groups of glucagon on its conformational properties and on its ability to activate rat liver adenylyl cyclase.", "content": "Trinitrophenyl groups have been specifically introduced into the alpha- and/or the epsilon-NH2 groups of glucagon by reaction with trinitrobenzenesulfonic acid. Introduction of this group into the epsilon-NH2 position of the hormone leads to an apparant increase in the helical content as measured by circular dichroism, while substitution on the alpha-NH2 position causes little change in this property. The usefulness of the trinitrophenyl group for the study of intramolecular singlet excitation transfer from tryptophan is suggested. The pK and reactivity of the amino groups, as measured by the pH dependence of the rate of reaction with trinitrobenzenesulfonic acid, showed that the two amino groups of glucagon have similar properties to those of small model peptides. The trinitrophenyl-glucagon derivatives have little or no activity in stimulating adenylyl cylase of rat liver. By comparison with previously reported results, this demonstrates that the effect of chemical modifications of the amino group on the biological activity of glucagon depends critically on the group which is introduced.", "contents": "The effects of the trinitrophenylation of the amino groups of glucagon on its conformational properties and on its ability to activate rat liver adenylyl cyclase. Trinitrophenyl groups have been specifically introduced into the alpha- and/or the epsilon-NH2 groups of glucagon by reaction with trinitrobenzenesulfonic acid. Introduction of this group into the epsilon-NH2 position of the hormone leads to an apparant increase in the helical content as measured by circular dichroism, while substitution on the alpha-NH2 position causes little change in this property. The usefulness of the trinitrophenyl group for the study of intramolecular singlet excitation transfer from tryptophan is suggested. The pK and reactivity of the amino groups, as measured by the pH dependence of the rate of reaction with trinitrobenzenesulfonic acid, showed that the two amino groups of glucagon have similar properties to those of small model peptides. The trinitrophenyl-glucagon derivatives have little or no activity in stimulating adenylyl cylase of rat liver. By comparison with previously reported results, this demonstrates that the effect of chemical modifications of the amino group on the biological activity of glucagon depends critically on the group which is introduced."}
{"id": "PMID:237569", "title": "Circular dichroism analysis of the secondary structure of Z protein and its complexes with bilirubin and other organic anions.", "content": "Circular dichroism (CD) methods were employed to study the conformation of Z protein and characterize its complexes with bilirubin and other organic anions. Z protein-bilirubin complexes exhibited a spectrum with overlapping ellipticity bands of opposite sign in the bilirubin absorption region. These results were compared with those obtained with ligandin, the other major organic anion binding protein of liver. Secondary structural differences between the two proteins were easily demonstrated since ligandin is predominantly an alpha-helical protein and Z features mainly beta-structure. Furthermore, the optical activity pattern generated by bilirubin binding to Z was virtually a mirror image of that of the ligandin bilirubin system. CD experiments were designed to study the direct transfer of bilirubin between Z protein and ligandin, and it was shown that both proteins have almost equal affinities for bilirubin. The bilirubin on Z was readily displaced by oleic acid and displaced to a lesser extent by sulfobromophthalein,", "contents": "Circular dichroism analysis of the secondary structure of Z protein and its complexes with bilirubin and other organic anions. Circular dichroism (CD) methods were employed to study the conformation of Z protein and characterize its complexes with bilirubin and other organic anions. Z protein-bilirubin complexes exhibited a spectrum with overlapping ellipticity bands of opposite sign in the bilirubin absorption region. These results were compared with those obtained with ligandin, the other major organic anion binding protein of liver. Secondary structural differences between the two proteins were easily demonstrated since ligandin is predominantly an alpha-helical protein and Z features mainly beta-structure. Furthermore, the optical activity pattern generated by bilirubin binding to Z was virtually a mirror image of that of the ligandin bilirubin system. CD experiments were designed to study the direct transfer of bilirubin between Z protein and ligandin, and it was shown that both proteins have almost equal affinities for bilirubin. The bilirubin on Z was readily displaced by oleic acid and displaced to a lesser extent by sulfobromophthalein,"}
{"id": "PMID:237570", "title": "The role of tryptophan residues and hydrophobic interaction in the binding of riboflavin in egg-yolk flavoprotein.", "content": "Egg-yolk flavoprotein has 7.2 tryptophan residues exposed, while the apoprotein shows an apparent exposure of 80 percent of these (5.7 residues) with dimethylsulphoxide as the perturbant. In the apoprotein at pH 6.9 only 4 groups are perturbed to ethylene glycol, 3.2 to glycerol and 1.4 to sucrose. Diminishing estimates of exposure obtained with increasing molecular diameter of the perturbant suggests that part of indole chromophores of apoprotein are located in \"crevices\" of the protein molecule. The apoprotein was treated with 2-hydroxy-5-nitrobenzyl bromide, H2O2 and N-bromosuccinimide under conditions designed to accomplish modification of tryptophan residues. Five to six of the eight tryptophans present in the protein were modified. Under these conditions the apoprotein completely looses its capacity for binding riboflavin and the fluorescent intensity of the protein at 360 nm is quenched at the same time to about 80 percent of its initial value. The presence of nonpolar amino acid residues on the surface of the apoprotein suggested the importance of hydrophobic interactions as the dominant factor controlling the binding of riboflavin. The hydrophobic probes Indocyanine green and 4-benzoylamide-4-aminostilbene-2,2-disulphonic acid bound to the apoprotein giving equimolar complexes with dissocation constants, KD 6.5-10(-7) M and 1.8-10(-6) M, respectively, Addition of an equimolar amount of riboflavin quantitatively displaced these dyes from their complexes with apoprotein as shown by spectrophotometric and spectrofluorometric studies.", "contents": "The role of tryptophan residues and hydrophobic interaction in the binding of riboflavin in egg-yolk flavoprotein. Egg-yolk flavoprotein has 7.2 tryptophan residues exposed, while the apoprotein shows an apparent exposure of 80 percent of these (5.7 residues) with dimethylsulphoxide as the perturbant. In the apoprotein at pH 6.9 only 4 groups are perturbed to ethylene glycol, 3.2 to glycerol and 1.4 to sucrose. Diminishing estimates of exposure obtained with increasing molecular diameter of the perturbant suggests that part of indole chromophores of apoprotein are located in \"crevices\" of the protein molecule. The apoprotein was treated with 2-hydroxy-5-nitrobenzyl bromide, H2O2 and N-bromosuccinimide under conditions designed to accomplish modification of tryptophan residues. Five to six of the eight tryptophans present in the protein were modified. Under these conditions the apoprotein completely looses its capacity for binding riboflavin and the fluorescent intensity of the protein at 360 nm is quenched at the same time to about 80 percent of its initial value. The presence of nonpolar amino acid residues on the surface of the apoprotein suggested the importance of hydrophobic interactions as the dominant factor controlling the binding of riboflavin. The hydrophobic probes Indocyanine green and 4-benzoylamide-4-aminostilbene-2,2-disulphonic acid bound to the apoprotein giving equimolar complexes with dissocation constants, KD 6.5-10(-7) M and 1.8-10(-6) M, respectively, Addition of an equimolar amount of riboflavin quantitatively displaced these dyes from their complexes with apoprotein as shown by spectrophotometric and spectrofluorometric studies."}
{"id": "PMID:237571", "title": "Comparative micelle structure. IV. The similarity between caprine alphas-casein and bovine alphas-3- casein.", "content": "The major component of caprine (goat) alphas-casein has been isolated by DEAE-and CM-cellulose chromatography in buffers containing urea and 2-mercaptoethanol. The protein has a molecular weight of 25700 as determined by gel filtration on Sepharose 6B in guanidine hydrochloride. Its composition, Asp17, Thr14, Ser14, Glu45, Pro18, Gly4, Ala10, Cys2, Val12, Met4, Ile12, Leu12, Tyr11, Phe8, His5, Lys22, Arg6, Trp2 and 7 phosphate residues, is much closer to that of bovine alphas3-casein than to bovine alphas1-casein. The caprin alphas-casein is more easily precipitated with Ca2+ than bovine alphas3-casein at 37 degrees C, pH 6.8, which in turn is more easily precipitated than bovine alphas1-casein.", "contents": "Comparative micelle structure. IV. The similarity between caprine alphas-casein and bovine alphas-3- casein. The major component of caprine (goat) alphas-casein has been isolated by DEAE-and CM-cellulose chromatography in buffers containing urea and 2-mercaptoethanol. The protein has a molecular weight of 25700 as determined by gel filtration on Sepharose 6B in guanidine hydrochloride. Its composition, Asp17, Thr14, Ser14, Glu45, Pro18, Gly4, Ala10, Cys2, Val12, Met4, Ile12, Leu12, Tyr11, Phe8, His5, Lys22, Arg6, Trp2 and 7 phosphate residues, is much closer to that of bovine alphas3-casein than to bovine alphas1-casein. The caprin alphas-casein is more easily precipitated with Ca2+ than bovine alphas3-casein at 37 degrees C, pH 6.8, which in turn is more easily precipitated than bovine alphas1-casein."}
{"id": "PMID:237572", "title": "The subunit structure of Pseudomonas cytochrome oxidase.", "content": "Pseudomonas cytochrome oxidase (EC 1.9.3.2) is composed of two subunits. Each subunit has a molecular weight of approx. 63000 and, according to the iron determination, contains two hemes. Cytochrome oxidase was subjected to various dissociation procedures to determine the stability of the dimeric structure. Progressive succinylation of 14 to 68% of the lysine residues of the enzyme increases the amount of the protein appearing  in the subunit form (S20,W approximately 4 S) from 18 to 92%. At a high degree of succinylation a component with a sedimentation coefficient of approx. 2 S appears. The subunits with sedimentation coefficients of approx. 4 S and 2 S are also formed when the pH is below 4 or above 11. The same molecular weight (63000) was found for these two components in sodium dodecylsulphate electrophoresis. No dissociation of cytochrome oxidase was observed in salt solutions like 3 M NaC1 and 1 M Na2SO4, or in 6 M urea. The slight decrease in the sedimentation coefficients in NaC1 solutions is partly explained by preferential hydratation of the protein.", "contents": "The subunit structure of Pseudomonas cytochrome oxidase. Pseudomonas cytochrome oxidase (EC 1.9.3.2) is composed of two subunits. Each subunit has a molecular weight of approx. 63000 and, according to the iron determination, contains two hemes. Cytochrome oxidase was subjected to various dissociation procedures to determine the stability of the dimeric structure. Progressive succinylation of 14 to 68% of the lysine residues of the enzyme increases the amount of the protein appearing  in the subunit form (S20,W approximately 4 S) from 18 to 92%. At a high degree of succinylation a component with a sedimentation coefficient of approx. 2 S appears. The subunits with sedimentation coefficients of approx. 4 S and 2 S are also formed when the pH is below 4 or above 11. The same molecular weight (63000) was found for these two components in sodium dodecylsulphate electrophoresis. No dissociation of cytochrome oxidase was observed in salt solutions like 3 M NaC1 and 1 M Na2SO4, or in 6 M urea. The slight decrease in the sedimentation coefficients in NaC1 solutions is partly explained by preferential hydratation of the protein."}
{"id": "PMID:237573", "title": "Inhibition of pyruvate transport by fatty acids in isolated cells from rat small intestine.", "content": "1. A technique is described for the rapid separation of intestinal epithelial cells from the incubation medium by passage through a silicon-oil layer and collection in acid, in which their soluble constituents are released. 2. The inhibition by fatty acids of pyruvate oxidation is further studied. Measurement  of pyruvate transport in epithelial cells at 0 degree C showed that short- and medium-chain fatty acids as well as ricinoleate inhibit this transport. Propionate inhibits pyruvate transport by another mechanism than octanoate. 3. Differences between pyruvate propionate and octanoate transport across the epithelial cell membrane were obtained in efflux studies. These studies revealed that acetate, propionate, butyrate and high concentrations of bicarbonate readily stimulate the efflux of pyruvate, probably by anionic counter-transport. No effects were seen with octanoate and hexanoate. The data obtained in these efflux studies suggest that lipophilicity and the pKa values of the monocarboxylic acids determine the contribution of non-ionic diffusion to overall transport. 4. Saturation kinetics, competitive inhibition by short-chain fatty acids and counter-transport suggest a carrier-mediated transport of pyruvate.", "contents": "Inhibition of pyruvate transport by fatty acids in isolated cells from rat small intestine. 1. A technique is described for the rapid separation of intestinal epithelial cells from the incubation medium by passage through a silicon-oil layer and collection in acid, in which their soluble constituents are released. 2. The inhibition by fatty acids of pyruvate oxidation is further studied. Measurement  of pyruvate transport in epithelial cells at 0 degree C showed that short- and medium-chain fatty acids as well as ricinoleate inhibit this transport. Propionate inhibits pyruvate transport by another mechanism than octanoate. 3. Differences between pyruvate propionate and octanoate transport across the epithelial cell membrane were obtained in efflux studies. These studies revealed that acetate, propionate, butyrate and high concentrations of bicarbonate readily stimulate the efflux of pyruvate, probably by anionic counter-transport. No effects were seen with octanoate and hexanoate. The data obtained in these efflux studies suggest that lipophilicity and the pKa values of the monocarboxylic acids determine the contribution of non-ionic diffusion to overall transport. 4. Saturation kinetics, competitive inhibition by short-chain fatty acids and counter-transport suggest a carrier-mediated transport of pyruvate."}
{"id": "PMID:237574", "title": "Studies of normal and nephritic rat glomerular basement membrane.", "content": "Solubilization of the normal glomerular basement membrane with various solvents revealed that the material is held together by hydrogen and disulfide linkages as well as ionic salt bridges which ionize at around pH 10.0. Pronase digestion indicated that differences in susceptibility to enzyme digestion exist between normal and nephritic membrane. Titration of a urea-insoluble material indicated that some alteration must have taken place in the association between various components of the nephritic basement membrane. Chemical analysis of alkali-solubilized fractions suggested that greater alkali susceptibility of the nephritic material may be present. A collagen-like material resembling both tendon and dog basement membrane collagen in its amino acid composition was isolated. It contained 10% hexose, but in addition to glucose and galactose, mannose was also detected. A glycopeptide fraction obtained by pronase and collagenase digestion has a carbohydrate composition similar to the collagen-like material above. These substances probably represent incompletely digested fragments of the basement membrane.", "contents": "Studies of normal and nephritic rat glomerular basement membrane. Solubilization of the normal glomerular basement membrane with various solvents revealed that the material is held together by hydrogen and disulfide linkages as well as ionic salt bridges which ionize at around pH 10.0. Pronase digestion indicated that differences in susceptibility to enzyme digestion exist between normal and nephritic membrane. Titration of a urea-insoluble material indicated that some alteration must have taken place in the association between various components of the nephritic basement membrane. Chemical analysis of alkali-solubilized fractions suggested that greater alkali susceptibility of the nephritic material may be present. A collagen-like material resembling both tendon and dog basement membrane collagen in its amino acid composition was isolated. It contained 10% hexose, but in addition to glucose and galactose, mannose was also detected. A glycopeptide fraction obtained by pronase and collagenase digestion has a carbohydrate composition similar to the collagen-like material above. These substances probably represent incompletely digested fragments of the basement membrane."}
{"id": "PMID:237577", "title": "Chicken fumarase. II. Kinetic studies.", "content": "The catalysis of the hydration of fumarate and deshydration of L - malate by chicken fumarase was measured spectrophotometrically over a range of substrate concentrations from 4 times 10(-3) M to 8 times 10(-5) M for fumarate and from 8 times 10(-2) M to 10(-3) M for L - malate. For the forward and reverse reactions, linear Lineweaver and Burk plots were obtained. The Michaelis constants and the maximum initial velocities for both substrates were determined and the Haldane relation was found to be obeyed. The effect of pH on activity was investigated over a pH range from 5.5 to 9.0 and the data indicate the presence, in the active site, of two ionizable groups, one in the acidic form and one in the basic form. The values of the ionization constants, determined for the enzyme - substrate complexes, agree closely with the ones obtained for the porcine enzyme. The mode of action of twenty-four structural analogs on the initial velocity of the dehydration of L-malate, by chicken fumarase was examined. From these studies, two regions positively charged appear necessary for the effective binding of the carboxylates of the substrates and competitive inhibitors to the active center. Moreover, the data suggest the presence of an additional group, in the catalytic site of chicken fumarase, that stabilizes the carbon-carbon double bond common to fumarate and its structural analogs. Finally, from the comparison of the kinetic properties of the chicken and pig fumarases, it may be concluded that the catalytic mechanism of the homologous enzymes are very similar, if not identical.", "contents": "Chicken fumarase. II. Kinetic studies. The catalysis of the hydration of fumarate and deshydration of L - malate by chicken fumarase was measured spectrophotometrically over a range of substrate concentrations from 4 times 10(-3) M to 8 times 10(-5) M for fumarate and from 8 times 10(-2) M to 10(-3) M for L - malate. For the forward and reverse reactions, linear Lineweaver and Burk plots were obtained. The Michaelis constants and the maximum initial velocities for both substrates were determined and the Haldane relation was found to be obeyed. The effect of pH on activity was investigated over a pH range from 5.5 to 9.0 and the data indicate the presence, in the active site, of two ionizable groups, one in the acidic form and one in the basic form. The values of the ionization constants, determined for the enzyme - substrate complexes, agree closely with the ones obtained for the porcine enzyme. The mode of action of twenty-four structural analogs on the initial velocity of the dehydration of L-malate, by chicken fumarase was examined. From these studies, two regions positively charged appear necessary for the effective binding of the carboxylates of the substrates and competitive inhibitors to the active center. Moreover, the data suggest the presence of an additional group, in the catalytic site of chicken fumarase, that stabilizes the carbon-carbon double bond common to fumarate and its structural analogs. Finally, from the comparison of the kinetic properties of the chicken and pig fumarases, it may be concluded that the catalytic mechanism of the homologous enzymes are very similar, if not identical."}
{"id": "PMID:237578", "title": "[Purification and characterization of two peroxidases from hard wheat].", "content": "Two peroxidases A and B were purified from a borate buffer extract (pH = 10,4) of durum wheat semolina (Triticum durum), var. Bidi 17, by chromatography on DEAE-cellulose, salting out by 3M ammonium sulphate and two chromatographies on CM-cellulose; specific activities of peroxidase A or B were increased 114 or 66 fold. Molecular weight, amino acid composition, absorption spectrum, pH optimum, thermal stability and KM values differentiate the two enzymes. Ion Ca++ was shown as an activator of both peroxidase activities; the presence of an inhibitor in the crude extract was demonstrated.", "contents": "[Purification and characterization of two peroxidases from hard wheat]. Two peroxidases A and B were purified from a borate buffer extract (pH = 10,4) of durum wheat semolina (Triticum durum), var. Bidi 17, by chromatography on DEAE-cellulose, salting out by 3M ammonium sulphate and two chromatographies on CM-cellulose; specific activities of peroxidase A or B were increased 114 or 66 fold. Molecular weight, amino acid composition, absorption spectrum, pH optimum, thermal stability and KM values differentiate the two enzymes. Ion Ca++ was shown as an activator of both peroxidase activities; the presence of an inhibitor in the crude extract was demonstrated."}
{"id": "PMID:237575", "title": "[Study of conformational transformations in serum albumin by the method of scanning microcalorimetry].", "content": "Thermal denaturation of serum albumin in the alkali pH region is investigated by the scanning microcalorimetry method. It is shown that at pH 8.5 a macromolecule undergoes a conformational transformation as a result of which its thermal characteristics are changed qualitatively. The form which corresponds to lower pH values is denatured according to the smaller than all or none greater than model with an intensive sorption of heat. The form corresponding to higher pH values is denatured noncooperatively without heat absorption but with an essential increase of heat capacity.", "contents": "[Study of conformational transformations in serum albumin by the method of scanning microcalorimetry]. Thermal denaturation of serum albumin in the alkali pH region is investigated by the scanning microcalorimetry method. It is shown that at pH 8.5 a macromolecule undergoes a conformational transformation as a result of which its thermal characteristics are changed qualitatively. The form which corresponds to lower pH values is denatured according to the smaller than all or none greater than model with an intensive sorption of heat. The form corresponding to higher pH values is denatured noncooperatively without heat absorption but with an essential increase of heat capacity."}
{"id": "PMID:237579", "title": "Studies on changes in DNA polymerase activity during the cell cycle in synchronized KB cells.", "content": "We have demonstrated the presence of two DNA polymerases in KB cells and studied the variation of their activities in a synchronous cell population. During the cell cycle we observed in nuclei, only one DNA dependent DNA polymerase, the 3.4 S or minipolymerase, and similarly in the cytoplasm only one enzyme, the 8.3 S or maxipolymerase. The former shows preference for native DNA and the latter for denatured DNA. Their Mg++ and K+ requirements are different and their pH optima are 8.5 and 7 for nuclear polymerase and cytoplasmic polymerase respectively. The cytoplasmic polymerase activity remains stable from one cell cycle to the other with each cell reconstituting its stock at the start of the following cycle (G1 and early S phases). On the contrary nuclear activity decreases in G2, M and early G1, then increases to a maximum in the middle of the S phase. This fluctuation in enzyme activity could be due to degradation, transfer to the cytoplasm or the association of the enzyme with the chromatin and/or the nuclear membrane after completion of DNA synthesis. Our results do not permit us to choose between these three hypotheses. However their significance is discussed in the light of the results obtained by some authors who, on the contrary, have tended to minimise the role of the minipolymerase in DNA duplication, whereas we, from our findings, ascribe a preponderant role to this enzyme. The cytoplasmic maxipolymerase (8.3 S) may simply be a storage form of the enzyme from which minipolymerase can be formed as needed.", "contents": "Studies on changes in DNA polymerase activity during the cell cycle in synchronized KB cells. We have demonstrated the presence of two DNA polymerases in KB cells and studied the variation of their activities in a synchronous cell population. During the cell cycle we observed in nuclei, only one DNA dependent DNA polymerase, the 3.4 S or minipolymerase, and similarly in the cytoplasm only one enzyme, the 8.3 S or maxipolymerase. The former shows preference for native DNA and the latter for denatured DNA. Their Mg++ and K+ requirements are different and their pH optima are 8.5 and 7 for nuclear polymerase and cytoplasmic polymerase respectively. The cytoplasmic polymerase activity remains stable from one cell cycle to the other with each cell reconstituting its stock at the start of the following cycle (G1 and early S phases). On the contrary nuclear activity decreases in G2, M and early G1, then increases to a maximum in the middle of the S phase. This fluctuation in enzyme activity could be due to degradation, transfer to the cytoplasm or the association of the enzyme with the chromatin and/or the nuclear membrane after completion of DNA synthesis. Our results do not permit us to choose between these three hypotheses. However their significance is discussed in the light of the results obtained by some authors who, on the contrary, have tended to minimise the role of the minipolymerase in DNA duplication, whereas we, from our findings, ascribe a preponderant role to this enzyme. The cytoplasmic maxipolymerase (8.3 S) may simply be a storage form of the enzyme from which minipolymerase can be formed as needed."}
{"id": "PMID:237576", "title": "[Spectral-luminescent study of pH-dependent conformational changes in fibrinogen].", "content": "Results are presented of measurements of fluorescence parameters of fibrinogen at pH values of 2-12. It is stated that the stability zone of native conformation of fibrinogen molecule lies in the pH range of 5,5-8,5. In an acid medium the fibrinogen molecule twice (in the pH range of 5--3 and 3--2) undergoes structural rearrangement. In an alkali medium the structural rearrangement of fibrinogen is observed at pH greater than 9,5.", "contents": "[Spectral-luminescent study of pH-dependent conformational changes in fibrinogen]. Results are presented of measurements of fluorescence parameters of fibrinogen at pH values of 2-12. It is stated that the stability zone of native conformation of fibrinogen molecule lies in the pH range of 5,5-8,5. In an acid medium the fibrinogen molecule twice (in the pH range of 5--3 and 3--2) undergoes structural rearrangement. In an alkali medium the structural rearrangement of fibrinogen is observed at pH greater than 9,5."}
{"id": "PMID:237580", "title": "[Dextran glucosidase activity of the acid alpha-glucosidase from pig spleen].", "content": "Some properties of acid alpha-glucosidase from pig spleen are studied. Changes in the enzyme activity with respect to polymeric and oligomeric substrates were shown to take place under effects of temperature, pH, concentration of metal ions, urea treatment, trehalose inhibition. Dextran and glycogen were used as polymeric substrates, and disaccharides with different types of bonds were taken as oligomeric substrates. The data obtained confirm the hypothesis on separate regions of binding polymers and oligomers with the enzyme molecule.", "contents": "[Dextran glucosidase activity of the acid alpha-glucosidase from pig spleen]. Some properties of acid alpha-glucosidase from pig spleen are studied. Changes in the enzyme activity with respect to polymeric and oligomeric substrates were shown to take place under effects of temperature, pH, concentration of metal ions, urea treatment, trehalose inhibition. Dextran and glycogen were used as polymeric substrates, and disaccharides with different types of bonds were taken as oligomeric substrates. The data obtained confirm the hypothesis on separate regions of binding polymers and oligomers with the enzyme molecule."}
{"id": "PMID:237581", "title": "[Isolation and some properties of exoribonuclease from the cell nuclei of the rat liver].", "content": "Exoribonuclease from rat liver cell nuclei was isolated and purified using selective extraction at pH 8.0, salting out with ammonium sulfate (30-50% saturation) and chromatography on DEAE-Sephadex A-50. The enzyme has the pH optimum 7.4-7.6, it requires Mg-2+. It catalyses the gradual removal of ribonucleoside-5'-monophosphates from synthetic polynucleotides and RNA; it preferably attacks single-stranded polynucleotides and is less efficient when hydrolysing poly-stranded helical polymers. It is supposed that exoribonuclease can participate in the destruction of non-informative regions in new-formed hyper-molecular RNA of cell nuclei.", "contents": "[Isolation and some properties of exoribonuclease from the cell nuclei of the rat liver]. Exoribonuclease from rat liver cell nuclei was isolated and purified using selective extraction at pH 8.0, salting out with ammonium sulfate (30-50% saturation) and chromatography on DEAE-Sephadex A-50. The enzyme has the pH optimum 7.4-7.6, it requires Mg-2+. It catalyses the gradual removal of ribonucleoside-5'-monophosphates from synthetic polynucleotides and RNA; it preferably attacks single-stranded polynucleotides and is less efficient when hydrolysing poly-stranded helical polymers. It is supposed that exoribonuclease can participate in the destruction of non-informative regions in new-formed hyper-molecular RNA of cell nuclei."}
{"id": "PMID:237582", "title": "[Interaction of aspartate transaminase from chicken heart cytosol with pyridoxal phosphate analogs].", "content": "The interactions were studied of the apoenzyme of aspartate aminotransferase from chicken heart cytosol with a variety of pyridoxal-P analogues. 2-Norpyridoxal-P, 2'-n-propylpyridoxal-P, 2'-isopropylpyridoxal-P, 6-methylpyridoxal-P, and 5'-methylpyridoxal-P were shown to display coenzyme activity. Estimated relative Vmax values of the complexes of apoenzyme with the above--mentioned analogues amounted respectively to 0.8; 0,2; 0,1; 0.1 and 0.1 (taking the Vmax value of the native holoenzyme as equal 1.0). The pH-dependence of reactivation rates of the apoenzyme with pyridoxal-P and pyridoxamine-P was evaluated. 3-Deoxypyridoxal-P, 3-0-methylpyridoxal-P, 2'-phenylpyridoxal-P, 5-nor-5-beta-carboxyvinylpyridoxal and 5-nor-5-beta-carboxyethylpyridoxal fail to activate the apoenzyme, but inhibit competitively the binding of pyridoxal-P to the protein; the estimated Ki values for these analoges were 2.4-10- minus 6; 3.1-10- minus 6; 3.5-10- minus 6; 7.2-10- minus 6 and 8.3-10- minus 6 M, respectively. It is of interest to compare reactivation effects of pyridoxal-P analogues for the apoenzymes of aspartate aminotransferases from chicken and from pig heart cytosol. Although the observed effects were fairly similar, it should be noted that the relative catalytic efficiencies of complexes of the chicken apoenzyme with pyridoxal-P analogues were much lower than those of complexes formed with the pig heart apoenzyme. It thus appears that of the two enzymes tested, the chicken heart aminotransferase makes more stringent demands with respect to structure of the coenzyme.", "contents": "[Interaction of aspartate transaminase from chicken heart cytosol with pyridoxal phosphate analogs]. The interactions were studied of the apoenzyme of aspartate aminotransferase from chicken heart cytosol with a variety of pyridoxal-P analogues. 2-Norpyridoxal-P, 2'-n-propylpyridoxal-P, 2'-isopropylpyridoxal-P, 6-methylpyridoxal-P, and 5'-methylpyridoxal-P were shown to display coenzyme activity. Estimated relative Vmax values of the complexes of apoenzyme with the above--mentioned analogues amounted respectively to 0.8; 0,2; 0,1; 0.1 and 0.1 (taking the Vmax value of the native holoenzyme as equal 1.0). The pH-dependence of reactivation rates of the apoenzyme with pyridoxal-P and pyridoxamine-P was evaluated. 3-Deoxypyridoxal-P, 3-0-methylpyridoxal-P, 2'-phenylpyridoxal-P, 5-nor-5-beta-carboxyvinylpyridoxal and 5-nor-5-beta-carboxyethylpyridoxal fail to activate the apoenzyme, but inhibit competitively the binding of pyridoxal-P to the protein; the estimated Ki values for these analoges were 2.4-10- minus 6; 3.1-10- minus 6; 3.5-10- minus 6; 7.2-10- minus 6 and 8.3-10- minus 6 M, respectively. It is of interest to compare reactivation effects of pyridoxal-P analogues for the apoenzymes of aspartate aminotransferases from chicken and from pig heart cytosol. Although the observed effects were fairly similar, it should be noted that the relative catalytic efficiencies of complexes of the chicken apoenzyme with pyridoxal-P analogues were much lower than those of complexes formed with the pig heart apoenzyme. It thus appears that of the two enzymes tested, the chicken heart aminotransferase makes more stringent demands with respect to structure of the coenzyme."}
{"id": "PMID:237589", "title": "Studies on a circulating anticoagulant in systemic lupus erythematosus: evidence for inhibition of the function of activated plasma thromboplastin antecedent (factor XIa).", "content": "Plasma proteins which interfere with blood coagulation have often been described in patients with systemic lupus erythematosus (SLE). The most frequent type interferes with the conversion of prothrombin to thrombin and thus prolongs the prothrombin time. Infrequently, SLE patients exhibit anticoagulants which appear to block the earlier stages of coagulation such as those involving factor VIII or the formation of activated factor XI (factor XIa). The anticoagulant reported here was studied by means of a sequential clotting system utilizing crude coagulation factors and was noted to interfere with the action of activated plasma thromboplastin antecedent (PTA) during the activation of factor IX. This anticoagulant was found in gamma-globulin-rich ethanol fractions of plasma. After gel filtration, it was found principally in fractions containing IgM globulins but also, to a lesser extent, in IgG-rich fractions. In this respect, it is similar to anticoagulants reported in certain other cases of SLE. Attempts to confirm the immunoglobulin nature of the anticoagulant by immunoabsorption were, however, inconclusive", "contents": "Studies on a circulating anticoagulant in systemic lupus erythematosus: evidence for inhibition of the function of activated plasma thromboplastin antecedent (factor XIa). Plasma proteins which interfere with blood coagulation have often been described in patients with systemic lupus erythematosus (SLE). The most frequent type interferes with the conversion of prothrombin to thrombin and thus prolongs the prothrombin time. Infrequently, SLE patients exhibit anticoagulants which appear to block the earlier stages of coagulation such as those involving factor VIII or the formation of activated factor XI (factor XIa). The anticoagulant reported here was studied by means of a sequential clotting system utilizing crude coagulation factors and was noted to interfere with the action of activated plasma thromboplastin antecedent (PTA) during the activation of factor IX. This anticoagulant was found in gamma-globulin-rich ethanol fractions of plasma. After gel filtration, it was found principally in fractions containing IgM globulins but also, to a lesser extent, in IgG-rich fractions. In this respect, it is similar to anticoagulants reported in certain other cases of SLE. Attempts to confirm the immunoglobulin nature of the anticoagulant by immunoabsorption were, however, inconclusive"}
{"id": "PMID:237590", "title": "Platelet storage at 22 degrees C: role of gas transport across plastic containers in maintenance of viability.", "content": "Containers constructed of polyvinylchloride (PVC) are used for the storage of platelet concentrates (PC) for transfusion, At 22 degrees C, pH often falls to such low levels (pH is less that 6.0) that viability is lost. Far lesser degrees of pH fall are observed in bags constructed of polyethylene (PE). In this study, pH, PO2, PCO2, platelet count, lactate concentration, microscopic morphology, and viability after 51-chromium labeling were evaluated during storage at 22 degrees C under a variety of circumstances. The results indicate that (1) pH falls because of the generation of lactic acid by platelet glycolysis and, under some circumstances, the retention of CO2. (2) Rate of pH fall is, therefore, roughly proportional to the platelet count. (3) PE is more permeable to gases, thereby allowing CO2 escape from and easier O2 entry into the stored PC; the higher O2 tensions suppress glycolysis by the Pasteur effect. (4) Adequate agitation and container size are critical if the beneficial effect of PE is to be obtained. (5) In general, platelets stored in PE containers have excellent viability in vivo although CO2 escape can result in elevations in pH which are deleterious. (6) Storage in a 10% CO2 atmosphere prevents these deletrrious pH elevations without otherwise impairing platelet viability; (7) Results similar to those achieved with PE can be achieved with PVC if this material is made thinner to allow easier penetration of gases", "contents": "Platelet storage at 22 degrees C: role of gas transport across plastic containers in maintenance of viability. Containers constructed of polyvinylchloride (PVC) are used for the storage of platelet concentrates (PC) for transfusion, At 22 degrees C, pH often falls to such low levels (pH is less that 6.0) that viability is lost. Far lesser degrees of pH fall are observed in bags constructed of polyethylene (PE). In this study, pH, PO2, PCO2, platelet count, lactate concentration, microscopic morphology, and viability after 51-chromium labeling were evaluated during storage at 22 degrees C under a variety of circumstances. The results indicate that (1) pH falls because of the generation of lactic acid by platelet glycolysis and, under some circumstances, the retention of CO2. (2) Rate of pH fall is, therefore, roughly proportional to the platelet count. (3) PE is more permeable to gases, thereby allowing CO2 escape from and easier O2 entry into the stored PC; the higher O2 tensions suppress glycolysis by the Pasteur effect. (4) Adequate agitation and container size are critical if the beneficial effect of PE is to be obtained. (5) In general, platelets stored in PE containers have excellent viability in vivo although CO2 escape can result in elevations in pH which are deleterious. (6) Storage in a 10% CO2 atmosphere prevents these deletrrious pH elevations without otherwise impairing platelet viability; (7) Results similar to those achieved with PE can be achieved with PVC if this material is made thinner to allow easier penetration of gases"}
{"id": "PMID:237591", "title": "The effect of carbon monoxide on red cell life span in sickle cell disease.", "content": "Carbon monoxide at a concentration of 1000-2000 ppm was administered to sickle cell disease patients. In each of two patients, one 51Cr red cell survival study was carried out before CO administration, and a second study was initiated a few days before CO administration was started. In both, significant prolongation of red cell survival was observed, suggesting that the rheologic properties of sickle cells were favorably influenced in vivo. The administration of carbon monoxide is not recommended as a treatment for sickle cell disease. However, further trials would seem to be justified if conducted under carefully controlled conditions.", "contents": "The effect of carbon monoxide on red cell life span in sickle cell disease. Carbon monoxide at a concentration of 1000-2000 ppm was administered to sickle cell disease patients. In each of two patients, one 51Cr red cell survival study was carried out before CO administration, and a second study was initiated a few days before CO administration was started. In both, significant prolongation of red cell survival was observed, suggesting that the rheologic properties of sickle cells were favorably influenced in vivo. The administration of carbon monoxide is not recommended as a treatment for sickle cell disease. However, further trials would seem to be justified if conducted under carefully controlled conditions."}
{"id": "PMID:237583", "title": "[Effect of nucleophiles on the conversion of choline esters under the action of cholinesterase].", "content": "It is shown that effect of alcohols ROH on the hydrolysis of butyryl-choline and acetylcholine by choline esterase (E. C. 3.1.1.8) is complex; it included the concurrent and the unconcurrent inhibitions, the interaction with the acylenzyme to form more reactive triple complex, and the acyl migration. By titrometric method it is found that proportion of the transacylation and hydrolysis rates depends on hydrophobity of R only being independent on its electronegativity.", "contents": "[Effect of nucleophiles on the conversion of choline esters under the action of cholinesterase]. It is shown that effect of alcohols ROH on the hydrolysis of butyryl-choline and acetylcholine by choline esterase (E. C. 3.1.1.8) is complex; it included the concurrent and the unconcurrent inhibitions, the interaction with the acylenzyme to form more reactive triple complex, and the acyl migration. By titrometric method it is found that proportion of the transacylation and hydrolysis rates depends on hydrophobity of R only being independent on its electronegativity."}
{"id": "PMID:237584", "title": "[Some properties of beta-aspartate kinase from Micrococcus glutamicus-95 bacteria].", "content": "Kinetic and allosteric properties of beta-asparatatekinase from Micrococcus glutamicus-95 were studied. Coarse protein fraction, sedimented at 0.8 from saturated (NH4)2SO4, was used as an enzyme preparation. Curves of the dependency of the enzymatic reaction rate on substrate (L-aspartic acid and ATP) concentration were not found to be S-like. However, double reciprocal plotting of the data obtained revealed their deviation from the hyperbolic curve. The effect of amino acids (lysine, threonine, isoleucine, valine) on the activity of beta-aspartatekinase is studied. Lysine was shown to inhibit slightly beta-aspartatekinase, while threonine slightly activated it. Combined addition of both amino acids at a concentration of 1 mM resulted in the 50% inhibition. Isoleucine and valine activated beta-aspartatekinase and eliminated multivalent inhibitory effect of lysine and threonine. Interaction of isoleucine and lysine+threonine with beta-aspartatekinase was competitive with respect to L-aspartic acid and non-competitive in relation to ATP.", "contents": "[Some properties of beta-aspartate kinase from Micrococcus glutamicus-95 bacteria]. Kinetic and allosteric properties of beta-asparatatekinase from Micrococcus glutamicus-95 were studied. Coarse protein fraction, sedimented at 0.8 from saturated (NH4)2SO4, was used as an enzyme preparation. Curves of the dependency of the enzymatic reaction rate on substrate (L-aspartic acid and ATP) concentration were not found to be S-like. However, double reciprocal plotting of the data obtained revealed their deviation from the hyperbolic curve. The effect of amino acids (lysine, threonine, isoleucine, valine) on the activity of beta-aspartatekinase is studied. Lysine was shown to inhibit slightly beta-aspartatekinase, while threonine slightly activated it. Combined addition of both amino acids at a concentration of 1 mM resulted in the 50% inhibition. Isoleucine and valine activated beta-aspartatekinase and eliminated multivalent inhibitory effect of lysine and threonine. Interaction of isoleucine and lysine+threonine with beta-aspartatekinase was competitive with respect to L-aspartic acid and non-competitive in relation to ATP."}
{"id": "PMID:237594", "title": "Dissociation of theophylline uptake and inotropic effect in myocardial tissue: influence of temperature, pH and calcium.", "content": "1. The myocardial uptake and the positive inotropic effect of theophylline (100 mug/ml; 0.56 mM) were studied in isolated electrically driven guinea-pig hearts perfused by the Langendorff technique under various extracellular conditions. [3H]-theophylline was used. 2. Variations in temperature, hydrogen ion and calcium ion concentrations of the perfusion media changed the time course and magnitude of the effect of theophylline on myocardial twitch tension but did not affect the time course and amount of theophylline uptake. 3. Under all conditions, the build-up of the positive inotropic effect of theophylline was about three times faster than the uptake of the drug into the heart. 4. Since no relationship could be found between theophylline uptake and inotropic effect, the cardiac positive inotropic response to theophylline is thought unlikely to be due mainly to an interaction of the drug with intracellular receptor sites but is assumed to occur via an effect of the drug on the sarcolemma, that is at a site which the drug reaches before it enters the intracellular space.", "contents": "Dissociation of theophylline uptake and inotropic effect in myocardial tissue: influence of temperature, pH and calcium. 1. The myocardial uptake and the positive inotropic effect of theophylline (100 mug/ml; 0.56 mM) were studied in isolated electrically driven guinea-pig hearts perfused by the Langendorff technique under various extracellular conditions. [3H]-theophylline was used. 2. Variations in temperature, hydrogen ion and calcium ion concentrations of the perfusion media changed the time course and magnitude of the effect of theophylline on myocardial twitch tension but did not affect the time course and amount of theophylline uptake. 3. Under all conditions, the build-up of the positive inotropic effect of theophylline was about three times faster than the uptake of the drug into the heart. 4. Since no relationship could be found between theophylline uptake and inotropic effect, the cardiac positive inotropic response to theophylline is thought unlikely to be due mainly to an interaction of the drug with intracellular receptor sites but is assumed to occur via an effect of the drug on the sarcolemma, that is at a site which the drug reaches before it enters the intracellular space."}
{"id": "PMID:237599", "title": "Role of IgG fractions with high isoelectric points in the thymol turbidity test in syphilis. Evidence for an increase in basic IgG in early syphilis.", "content": "It is demonstrated that IgG fractions with isoelectric points above 7.6, isolated from pooled syphilitic sera, are able to elevate the thymol turbidity. The effect increases with increasing isoelectric points of the isolated fraction. IgG from individual syphilitic patients exerts a stronger effect on the thymol turbidity than normal IgG. It is concluded that elevated amounts of these basic immunoglobulins are present in the sera of syphilitic subjects.", "contents": "Role of IgG fractions with high isoelectric points in the thymol turbidity test in syphilis. Evidence for an increase in basic IgG in early syphilis. It is demonstrated that IgG fractions with isoelectric points above 7.6, isolated from pooled syphilitic sera, are able to elevate the thymol turbidity. The effect increases with increasing isoelectric points of the isolated fraction. IgG from individual syphilitic patients exerts a stronger effect on the thymol turbidity than normal IgG. It is concluded that elevated amounts of these basic immunoglobulins are present in the sera of syphilitic subjects."}
{"id": "PMID:237600", "title": "Preference for basic IgG in early syphilis.", "content": "By differential IgG measurements of sera of 27 patients with early infectious syphilis, it was found that infection with T. pallidium results in a preferential synthesis of IgG immunoglobulins characterized by high isoelectric points. The decrease in total IgG level observed after 6 weeks of treatment can to a large extent be accounted for by the decrease in basic IgG concentration. The relationship between the total and basic IgG levels and the number of T. pallidum present in the body during the three early stages of the disease studied is discussed.", "contents": "Preference for basic IgG in early syphilis. By differential IgG measurements of sera of 27 patients with early infectious syphilis, it was found that infection with T. pallidium results in a preferential synthesis of IgG immunoglobulins characterized by high isoelectric points. The decrease in total IgG level observed after 6 weeks of treatment can to a large extent be accounted for by the decrease in basic IgG concentration. The relationship between the total and basic IgG levels and the number of T. pallidum present in the body during the three early stages of the disease studied is discussed."}
{"id": "PMID:237601", "title": "Effect of pentazocine on the evoked potentials recorded in the primary somesthetic cortical areas of guinea pigs.", "content": "The influence of pentazocine on the evoked potentials registered in the primary somesthetic cortical area in guinea pigs under pentobarbital anesthesia was studied. The stimulation was applied in the contralateral lip and the evoked cortical responses from different zones on the cortex stereotaxically localized were registered. Pentazocine (5-10 mg/kg i.v.) induced a significant increase in the latency of the evoked potentials as compared with controls. Since morphine does not modify these potentials, the effect of pentazocine is interpreted as being a direct one on the primary pain pathway.", "contents": "Effect of pentazocine on the evoked potentials recorded in the primary somesthetic cortical areas of guinea pigs. The influence of pentazocine on the evoked potentials registered in the primary somesthetic cortical area in guinea pigs under pentobarbital anesthesia was studied. The stimulation was applied in the contralateral lip and the evoked cortical responses from different zones on the cortex stereotaxically localized were registered. Pentazocine (5-10 mg/kg i.v.) induced a significant increase in the latency of the evoked potentials as compared with controls. Since morphine does not modify these potentials, the effect of pentazocine is interpreted as being a direct one on the primary pain pathway."}
{"id": "PMID:237604", "title": "The effects of axotomy on the development of the rat superior cervical ganglion.", "content": "The effects of division of the postganglionic axons of the adrenergic neurones in the superior cervical ganglion of the rat were examined with regard to the total ganglionic protein content and tyrosine hydroxylase and DOPA decarboxylase activities. Axotomy before the twelfth postnatal day results in a marked atrophy of the ganglion and a reduction in the total enzyme content of the ganglion. Axotomy after postnatal day 21 results in the normal adult ganglion response with a large increase in the total protein content of the ganglion and only minor changes in the total enzyme content of the ganglion. Axotomy between the postnatal days 12 and 21 results in an intermediate response. Thus it can be concluded there is a critical period during the development of the ganglion during which the adrenergic neurones undergo a maturation governed by their contact with the peripheral target cell via axons. These results suggest a trophic role of the end organ on the adrenergic neurone.", "contents": "The effects of axotomy on the development of the rat superior cervical ganglion. The effects of division of the postganglionic axons of the adrenergic neurones in the superior cervical ganglion of the rat were examined with regard to the total ganglionic protein content and tyrosine hydroxylase and DOPA decarboxylase activities. Axotomy before the twelfth postnatal day results in a marked atrophy of the ganglion and a reduction in the total enzyme content of the ganglion. Axotomy after postnatal day 21 results in the normal adult ganglion response with a large increase in the total protein content of the ganglion and only minor changes in the total enzyme content of the ganglion. Axotomy between the postnatal days 12 and 21 results in an intermediate response. Thus it can be concluded there is a critical period during the development of the ganglion during which the adrenergic neurones undergo a maturation governed by their contact with the peripheral target cell via axons. These results suggest a trophic role of the end organ on the adrenergic neurone."}
{"id": "PMID:237605", "title": "The effect of hydrocortisone and adrenocorticotrophic hormone on monoamine oxidase and tyrosine hydroxylase in explant cultures of embryonic chick sympathetic ganglia.", "content": "Sympathetic ganglia from 13- to 15-day-old embryonic chicks were cultured for up to 2 days in Leighton tubes. The influence of hydrocortisone and ACTH added to the culture medium on the enzymes monoamine oxidase (MAO) and tyrosine hydroxylase was studied. Hydrocortisone (5 times 10(-5)M) had no effect on tyrosine hydroxylase but increased MAO activity by up to 46 percent over control values under conditions of low or zero nerve growth factor (NGF) concentration. ACTH also increased ganglionic MAO activity, the effect again depending on NGF concentration. This time the maximal response (an increase of 50 percent over controls) was seen at high NGF concentrations. This response was similar to the effect of 1 mM dibutyryl cyclic AMP, and was blocked by 1 times 10-5 M propranolol and 10 muM prostaglandin E(1). ACTH only slightly increased tyrosine hydroxylase activity and this effect was due to a small (18 percent) increase in sympathetic neurone number. Guanosine 5-diphosphate (0.5 mM) was found to increase tyrosine hydroxylase activity by 57 percent and this effect was blocked by the presence of ACTH.", "contents": "The effect of hydrocortisone and adrenocorticotrophic hormone on monoamine oxidase and tyrosine hydroxylase in explant cultures of embryonic chick sympathetic ganglia. Sympathetic ganglia from 13- to 15-day-old embryonic chicks were cultured for up to 2 days in Leighton tubes. The influence of hydrocortisone and ACTH added to the culture medium on the enzymes monoamine oxidase (MAO) and tyrosine hydroxylase was studied. Hydrocortisone (5 times 10(-5)M) had no effect on tyrosine hydroxylase but increased MAO activity by up to 46 percent over control values under conditions of low or zero nerve growth factor (NGF) concentration. ACTH also increased ganglionic MAO activity, the effect again depending on NGF concentration. This time the maximal response (an increase of 50 percent over controls) was seen at high NGF concentrations. This response was similar to the effect of 1 mM dibutyryl cyclic AMP, and was blocked by 1 times 10-5 M propranolol and 10 muM prostaglandin E(1). ACTH only slightly increased tyrosine hydroxylase activity and this effect was due to a small (18 percent) increase in sympathetic neurone number. Guanosine 5-diphosphate (0.5 mM) was found to increase tyrosine hydroxylase activity by 57 percent and this effect was blocked by the presence of ACTH."}
{"id": "PMID:237608", "title": "Seasonal variation in semen characteristics of White Leghorn, New Hampshire and indigenous chicken in Iraq.", "content": "1. The effects of season, temperature, humidity and light on semen volume, pH, concentration, motility and the proportions of dead and abnormal spermatozoa were investigated on White Leghorn, New Hampshire and Iraqi cockerels. 2. All semen characteristics, with the exception of pH, were significantly influenced by season. 3. The semen quality of the Iraqi breed was similar to that of the New Hampshire breed.", "contents": "Seasonal variation in semen characteristics of White Leghorn, New Hampshire and indigenous chicken in Iraq. 1. The effects of season, temperature, humidity and light on semen volume, pH, concentration, motility and the proportions of dead and abnormal spermatozoa were investigated on White Leghorn, New Hampshire and Iraqi cockerels. 2. All semen characteristics, with the exception of pH, were significantly influenced by season. 3. The semen quality of the Iraqi breed was similar to that of the New Hampshire breed."}
{"id": "PMID:237610", "title": "A hazard associated with improper connection of the Bain breathing circuit.", "content": "A case of cardiac arrest is presented which was caused by improper connection of a modified Mapleson D circuit (Bain breathing circuit). Excessive enternal deadspace was created by interchanging the gas inflow line and the attachment for an airway pressure manometer. This resulted in a marked respiratory acidosis, clinically undetected until the concomitant hypoxia produced a severe cardiac depression and arrest. The sequence of events was reproduced in a dog under comparable anaesthetic conditions. In order to avoid this error it is recommended to permanently fuse the connecting piece placed in the circuit with the tubing leading to the airway pressure manometer of the respirator.", "contents": "A hazard associated with improper connection of the Bain breathing circuit. A case of cardiac arrest is presented which was caused by improper connection of a modified Mapleson D circuit (Bain breathing circuit). Excessive enternal deadspace was created by interchanging the gas inflow line and the attachment for an airway pressure manometer. This resulted in a marked respiratory acidosis, clinically undetected until the concomitant hypoxia produced a severe cardiac depression and arrest. The sequence of events was reproduced in a dog under comparable anaesthetic conditions. In order to avoid this error it is recommended to permanently fuse the connecting piece placed in the circuit with the tubing leading to the airway pressure manometer of the respirator."}
{"id": "PMID:237611", "title": "The effect of artificial ventilation on functional residual capacity and arterial oxygenation. II. Comparison of spontaneous respiration and artificial ventilation at similar arterial carbon dioxide tensions, tidal volumes and inspiratory gas flow rates.", "content": "We have compared cardiac output, gas exchange and pulmonary mechanics during spontaneous breathing and artificial ventilaton under conditions which kept PaCO2 within the normal range and maintained constant tidal volume and inspired gas flow rate. In dogs anaesthetized with pentobarbitone and ventilated with air, artificial ventilation increased VD/VT but did not reduce Q angstrom, FRC, or CL. PaO2 increased and A-aDO2 decreased during aritificial ventilation, perhaps because of a small increase in Q angstrom and a small decrease in oxygen consumption. It appears that many of the reported deleterious effects of artificial ventilation may be due to the use of other anaesthetic agents and patterns of ventilation, and to changes in PaCO2.", "contents": "The effect of artificial ventilation on functional residual capacity and arterial oxygenation. II. Comparison of spontaneous respiration and artificial ventilation at similar arterial carbon dioxide tensions, tidal volumes and inspiratory gas flow rates. We have compared cardiac output, gas exchange and pulmonary mechanics during spontaneous breathing and artificial ventilaton under conditions which kept PaCO2 within the normal range and maintained constant tidal volume and inspired gas flow rate. In dogs anaesthetized with pentobarbitone and ventilated with air, artificial ventilation increased VD/VT but did not reduce Q angstrom, FRC, or CL. PaO2 increased and A-aDO2 decreased during aritificial ventilation, perhaps because of a small increase in Q angstrom and a small decrease in oxygen consumption. It appears that many of the reported deleterious effects of artificial ventilation may be due to the use of other anaesthetic agents and patterns of ventilation, and to changes in PaCO2."}
{"id": "PMID:237612", "title": "Maternal and foetal effects of methoxyflurane anaesthesia in the pregnant ewe.", "content": "Maternal and foetal cardiovascular, blood gas and acid-base changes were studied during 90 minutes of methoxyflurane anaesthesia. At 1.0 and 1.5 MAC anaesthesia, despite slight to moderate falls in maternal blood pressure, cardiac output and uterine blood flow, no serious foetal deterioration was seen. 2.0 MAC methoxyflurane was associated with marked falls in maternal blood pressure, cardiac output and uterine blood flow. Foetal hypoxaemia and a mixed respiratory and metabolic acidosis developed. Little foetal cardiovascular depression was seen with any level of anaesthesia. There was no direct effect of methoxyflurane on the uterine vasculature.", "contents": "Maternal and foetal effects of methoxyflurane anaesthesia in the pregnant ewe. Maternal and foetal cardiovascular, blood gas and acid-base changes were studied during 90 minutes of methoxyflurane anaesthesia. At 1.0 and 1.5 MAC anaesthesia, despite slight to moderate falls in maternal blood pressure, cardiac output and uterine blood flow, no serious foetal deterioration was seen. 2.0 MAC methoxyflurane was associated with marked falls in maternal blood pressure, cardiac output and uterine blood flow. Foetal hypoxaemia and a mixed respiratory and metabolic acidosis developed. Little foetal cardiovascular depression was seen with any level of anaesthesia. There was no direct effect of methoxyflurane on the uterine vasculature."}
{"id": "PMID:237613", "title": "Doses of epinephrine causing arrhythmia during enflurane, methoxyflurane and halothane anaesthesia in dogs.", "content": "The arrhythmogenic dosage of epinephrine, administered by constant intravenous infusion, was measured in five dogs during enflurane, methoxyflurane and halothane anaesthesia. While premature ventricular contractions were observed in only one of five dogs with enflurane and methoxyflurane, epinephrine-induced arrhythmias were seen in all animals during halothane anaesthesia. Epinephrine dosage and the resultant increase in mean arterial blood pressure at which arrhythmias occurred during halothane anaesthesia were significantly less (p less than 0.05) than with the other anaesthetics. These observations indicate that enflurane and methoxyflurane, as compared to halothane, possess relatively less arrhythmogenic potential as sensitizing agents in the presence of increased circulating catecholamines.", "contents": "Doses of epinephrine causing arrhythmia during enflurane, methoxyflurane and halothane anaesthesia in dogs. The arrhythmogenic dosage of epinephrine, administered by constant intravenous infusion, was measured in five dogs during enflurane, methoxyflurane and halothane anaesthesia. While premature ventricular contractions were observed in only one of five dogs with enflurane and methoxyflurane, epinephrine-induced arrhythmias were seen in all animals during halothane anaesthesia. Epinephrine dosage and the resultant increase in mean arterial blood pressure at which arrhythmias occurred during halothane anaesthesia were significantly less (p less than 0.05) than with the other anaesthetics. These observations indicate that enflurane and methoxyflurane, as compared to halothane, possess relatively less arrhythmogenic potential as sensitizing agents in the presence of increased circulating catecholamines."}
{"id": "PMID:237615", "title": "A kinetic study of the reaction of horseradish peroxidase with hydrogen peroxide.", "content": "A kinetic study has been carried out over the pH range of 2.63-9.37 for the reaction of horseradish peroxidase with hydrogen peroxide to form compound I of th;e enzyme. Analysis of the results, indicates that there are two kinetic influencing, ionizable groups on the enzyme with pKa values of 3.2 and 3.9. Protonation of these groups results in a decrease in the rate of reaction of the enzyme with H2O2. A previous study of the kinetics of cyanide binding to horseradish peroxidase (Ellis, W.D. & Dunford, H.B.: Biochemistry 7, 2054-2062 (1968)) has been extended to down to pH 2.55, and analysis of these results also indicates the presence of two kinetically important ionizable groups on the enzyme with pKa values of 2.9 and 3.9.", "contents": "A kinetic study of the reaction of horseradish peroxidase with hydrogen peroxide. A kinetic study has been carried out over the pH range of 2.63-9.37 for the reaction of horseradish peroxidase with hydrogen peroxide to form compound I of th;e enzyme. Analysis of the results, indicates that there are two kinetic influencing, ionizable groups on the enzyme with pKa values of 3.2 and 3.9. Protonation of these groups results in a decrease in the rate of reaction of the enzyme with H2O2. A previous study of the kinetics of cyanide binding to horseradish peroxidase (Ellis, W.D. & Dunford, H.B.: Biochemistry 7, 2054-2062 (1968)) has been extended to down to pH 2.55, and analysis of these results also indicates the presence of two kinetically important ionizable groups on the enzyme with pKa values of 2.9 and 3.9."}
{"id": "PMID:237616", "title": "Distribution of dipeptidase activity between lysosomes and soluble fraction of rat liver.", "content": "Dipeptidase activity toward Arg-Phe, Arg-Gly, and Trp-Leu exhibited bimodal distribution in the lysosomal and soluble fractions of rat liver. The majority (50-70 percent) of the dipeptidase activity was present in the soluble fraction. Some evidence for a plasma membrane dipeptidase, which hydrolyzes Trp-Leu but not Arg-Phe or Arg-Gly, also was found. The lysosomal dipeptidase activity had a pH optimum of 6.0-7.0, and was activated by sulfhydryl reagents. Lysosomal localization for some of the dipeptidase activity was established with Triton WR-1339 fractionation and latency experiments.", "contents": "Distribution of dipeptidase activity between lysosomes and soluble fraction of rat liver. Dipeptidase activity toward Arg-Phe, Arg-Gly, and Trp-Leu exhibited bimodal distribution in the lysosomal and soluble fractions of rat liver. The majority (50-70 percent) of the dipeptidase activity was present in the soluble fraction. Some evidence for a plasma membrane dipeptidase, which hydrolyzes Trp-Leu but not Arg-Phe or Arg-Gly, also was found. The lysosomal dipeptidase activity had a pH optimum of 6.0-7.0, and was activated by sulfhydryl reagents. Lysosomal localization for some of the dipeptidase activity was established with Triton WR-1339 fractionation and latency experiments."}
{"id": "PMID:237617", "title": "Carboxylesterases (EC 3.1.1). The molecular sizes of chicken and pig liver carboxylesterases.", "content": "The molecular size of pig liver carboxylesterase has been investigated under a variety of conditions of pH and ionic strength. From equilibrium and velocity sedimentation at pH 4.0 and pH 7.5, and from chromatography on Sephadex G-200,we conclude that the monomeric molecular weight is similar to 65,000 daltons and that the enzyme associates to form trimers. Association equilibrium constants for the monomer-trimer system were estimated to be 0.02 1-2 g-2 at pH 4 (concentration-dependent molecular weight data) and 2 times 10-5 1-2g-2 at pH 7.5 (frontal gel chromatographic results). These studies were aided by comparisons of the properties of the pig liver enzyme with those of chicken liver carboxylesterase, which is shown to exhibit the velocity and equilibrium sedimentation characteristics of a homogeneous protein with molecular weight similar to 65,000. Studies of pig and chicken liver carboxylesterases in 6 M guanidinium chloride, 0.1 M in beta-mercaptoethanol, support the proposition that the monomeric species of these enzymes have molecular weights of similar to 65,000. On polyacrylamide gel electrophoresis in SDS, there is no evidence for a major species of molecular weight less than similar to 65,000 for the pig enzyme, but ca. 50 percent of the chicken esterase is dissociated into two species of molecular weight similar to 30,000.", "contents": "Carboxylesterases (EC 3.1.1). The molecular sizes of chicken and pig liver carboxylesterases. The molecular size of pig liver carboxylesterase has been investigated under a variety of conditions of pH and ionic strength. From equilibrium and velocity sedimentation at pH 4.0 and pH 7.5, and from chromatography on Sephadex G-200,we conclude that the monomeric molecular weight is similar to 65,000 daltons and that the enzyme associates to form trimers. Association equilibrium constants for the monomer-trimer system were estimated to be 0.02 1-2 g-2 at pH 4 (concentration-dependent molecular weight data) and 2 times 10-5 1-2g-2 at pH 7.5 (frontal gel chromatographic results). These studies were aided by comparisons of the properties of the pig liver enzyme with those of chicken liver carboxylesterase, which is shown to exhibit the velocity and equilibrium sedimentation characteristics of a homogeneous protein with molecular weight similar to 65,000. Studies of pig and chicken liver carboxylesterases in 6 M guanidinium chloride, 0.1 M in beta-mercaptoethanol, support the proposition that the monomeric species of these enzymes have molecular weights of similar to 65,000. On polyacrylamide gel electrophoresis in SDS, there is no evidence for a major species of molecular weight less than similar to 65,000 for the pig enzyme, but ca. 50 percent of the chicken esterase is dissociated into two species of molecular weight similar to 30,000."}
{"id": "PMID:237618", "title": "Carboxylesterases (EC 3.1.1). A comparison of some kinetic properties of horse, sheep, chicken, pig, and ox liver carboxylesterases.", "content": "A comparative study of the kinetic be,avior of horse, sheep, chicken, pig, and ox liver carboxylesterases is reported. The enzymes exhibit similar specificites towards a series of phenyl esters in which the acyl group is varied, and towards a series of butyrate esters in which the alcohol group is varied. Non-Michaelis-Menten kinetics are exhibited by the horse enzyme in the hydrolysis of methyl and ethyl butyrates, and by the pig enzyme with ethyl butyrate. Each enzyme exhibits inhibition by one or more substrates. A simple scheme which accounts for both activation and inhibition is discussed. pH-k(cat) profiles for the horse and chicken liver carboxylesterase-catalyzed hydrolyses of phenyl butyrate demonstrate dependencies on pK(a)S of 4.75 and 5.0, respectively.", "contents": "Carboxylesterases (EC 3.1.1). A comparison of some kinetic properties of horse, sheep, chicken, pig, and ox liver carboxylesterases. A comparative study of the kinetic be,avior of horse, sheep, chicken, pig, and ox liver carboxylesterases is reported. The enzymes exhibit similar specificites towards a series of phenyl esters in which the acyl group is varied, and towards a series of butyrate esters in which the alcohol group is varied. Non-Michaelis-Menten kinetics are exhibited by the horse enzyme in the hydrolysis of methyl and ethyl butyrates, and by the pig enzyme with ethyl butyrate. Each enzyme exhibits inhibition by one or more substrates. A simple scheme which accounts for both activation and inhibition is discussed. pH-k(cat) profiles for the horse and chicken liver carboxylesterase-catalyzed hydrolyses of phenyl butyrate demonstrate dependencies on pK(a)S of 4.75 and 5.0, respectively."}
{"id": "PMID:237619", "title": "Photooxidation of dinitrophenylhistidine-200 human carbonic anhydrase B.", "content": "Partial inactivation of tau-dinitrophenylhistidine-200 human carbonic anhydrase B, induced by visible light, followed first order kinetics (k(app) = 6.05 times 10-2 min-1). After 50 min the tau-dinitrophenylhistidine (tau-DNP-histidine) content decreased to a negligible level, but the illuminated enzyme retained, at pH 7.6, approximately 9.2 percent of the esterase activity of the native enzyme. The following lines of evidence suggest that the loss of activity results from the destruction of tau-DNP-histidine-200. (1) No significant loss of amino acid other than tau-DNP-histidine was detected after illumination. (2) The rate of loss of activity correlated well with the loss of tau-DNP-histidine. (3) In the photooxidized enzyme the DNP moiety was retained but had lost the characteristic sensitivity of tau-DNP-histidine to nucleophilic attack. Titration of the illuminated enzyme with acetazolamide indicated that the residual activity is an intrinsic property of the modified enzyme. The chromatographically purified photooxidized enzyme migrated as a single band on isoelectrofocusing in polyacylamide gel, and at pH 7.6 possessed 7.5 percent esterase activity relative to the native enzyme. By establishing effective destruction of histidine-200, it can be concluded that neither the pi N nor, as previously shown, the tau N of histidine-200 is critical for the catalysis.", "contents": "Photooxidation of dinitrophenylhistidine-200 human carbonic anhydrase B. Partial inactivation of tau-dinitrophenylhistidine-200 human carbonic anhydrase B, induced by visible light, followed first order kinetics (k(app) = 6.05 times 10-2 min-1). After 50 min the tau-dinitrophenylhistidine (tau-DNP-histidine) content decreased to a negligible level, but the illuminated enzyme retained, at pH 7.6, approximately 9.2 percent of the esterase activity of the native enzyme. The following lines of evidence suggest that the loss of activity results from the destruction of tau-DNP-histidine-200. (1) No significant loss of amino acid other than tau-DNP-histidine was detected after illumination. (2) The rate of loss of activity correlated well with the loss of tau-DNP-histidine. (3) In the photooxidized enzyme the DNP moiety was retained but had lost the characteristic sensitivity of tau-DNP-histidine to nucleophilic attack. Titration of the illuminated enzyme with acetazolamide indicated that the residual activity is an intrinsic property of the modified enzyme. The chromatographically purified photooxidized enzyme migrated as a single band on isoelectrofocusing in polyacylamide gel, and at pH 7.6 possessed 7.5 percent esterase activity relative to the native enzyme. By establishing effective destruction of histidine-200, it can be concluded that neither the pi N nor, as previously shown, the tau N of histidine-200 is critical for the catalysis."}
{"id": "PMID:237620", "title": "The lipopolysaccharides of Neisseria gonorrhoeae colony types 1 and 4.", "content": "The lipopolysaccharides (LPS) of strains of Neisseria gonorrhoeae grown in type 1 (T1) and 4 (T4) colony forms have been isolated. LPS from T4 colony type cells on mild hydrolysis gave a lipid A and a core oligosaccharide composed of 2-amino-2-deoxy-D-glucose, D-glucose, D-galactose, L-glycero-D-manno-heptose and 3-deoxy-D-manno-octuosonic acid that appeared to be common to all the strains examined. LPS from T1 colony type cells on mild hydrolysis gave a lipid A and high molecular weight O polysacc,arides which showed considerable differences in glycose composition for each strain examined. In those strains examined, T4 cells appear to produce a common \"R\" type LPS whereas T1 cells produce an \"S\" type LPS with structurally different O polysaccharide structures which probably account for serologically differentiated strains of N. gonorrhoeae.", "contents": "The lipopolysaccharides of Neisseria gonorrhoeae colony types 1 and 4. The lipopolysaccharides (LPS) of strains of Neisseria gonorrhoeae grown in type 1 (T1) and 4 (T4) colony forms have been isolated. LPS from T4 colony type cells on mild hydrolysis gave a lipid A and a core oligosaccharide composed of 2-amino-2-deoxy-D-glucose, D-glucose, D-galactose, L-glycero-D-manno-heptose and 3-deoxy-D-manno-octuosonic acid that appeared to be common to all the strains examined. LPS from T1 colony type cells on mild hydrolysis gave a lipid A and high molecular weight O polysacc,arides which showed considerable differences in glycose composition for each strain examined. In those strains examined, T4 cells appear to produce a common \"R\" type LPS whereas T1 cells produce an \"S\" type LPS with structurally different O polysaccharide structures which probably account for serologically differentiated strains of N. gonorrhoeae."}
{"id": "PMID:237621", "title": "The functional groups of the Mg-Ca ATPase from Escherichia coli.", "content": "The influence of hydrogen ion concentration on binding and conversion of MgATP and CaATP by membrane bound and solubilized ATPase from Escherichia coli has been investigated. The reaction of enzyme (E), hydrogen ion (H+), and substrate (S) procedes according to the following scheme, where Me is the metal ion and P is the product(s). (See article for formular). Within experimental error, the results obtained with membrane-bound and solubilized ATPase are identical. Changing the concentration of Mg2+ ions or replacement of Mg2+ by Ca2+ ions alters the dissociation constants Kb, KHMeATP, and Ka'. The kinetics and experiments with group-specific inhibitors suggest that integrity for amino, imidazole, tyrosyl, carboxyl, and arginyl residues is required for activity of membrane-bound and solubilized E. coli ATPase.", "contents": "The functional groups of the Mg-Ca ATPase from Escherichia coli. The influence of hydrogen ion concentration on binding and conversion of MgATP and CaATP by membrane bound and solubilized ATPase from Escherichia coli has been investigated. The reaction of enzyme (E), hydrogen ion (H+), and substrate (S) procedes according to the following scheme, where Me is the metal ion and P is the product(s). (See article for formular). Within experimental error, the results obtained with membrane-bound and solubilized ATPase are identical. Changing the concentration of Mg2+ ions or replacement of Mg2+ by Ca2+ ions alters the dissociation constants Kb, KHMeATP, and Ka'. The kinetics and experiments with group-specific inhibitors suggest that integrity for amino, imidazole, tyrosyl, carboxyl, and arginyl residues is required for activity of membrane-bound and solubilized E. coli ATPase."}
{"id": "PMID:237622", "title": "Wheat embryo ribonucleates. V. Generation of N2--dimethylguanylate when 'fully sequenced' homogeneous species of transfer RNA are used as substrates for wheat embryo methyltransferases.", "content": "When S-adenosly[methyl-14-C]methionine and various species of transfer RNA are used as substrates for wheat embryo methyltransferases, the principal site of guanylate-N-2 methylation can be shown to be a G-residue between the stems of the dihydrouridine and anticodon loops. This common site of guanylate-N-2 methylation is referred to as the interstem target site. 2. When the interstem target site is the non-terminal G-residue in a G-C-G-C sequence, as in the cases of Escherichia coli tRNA1-Leu, tRNA-Ile, and tRNA3-Ser, there is preponderant dimethylation to yield N-2-dimethylguanylate. 3. When the interstem target site is part of a U-C-G-U sequence, as in the case of E. coli tRNAf-Met, there is diminished dimethylation and correspondingly increased monomethylation to yield N-2-monomethylguanylate. 4. When the interstem target site is the non-terminal G-residue in an A-U-G-G sequence, as in the case of yeast tRNA-Asp, there is negligible dimethylation and almost exclusive monomethylation to yield N-2-monomethylguanylate. 5. The concerted way in which the primary, secondary, and tertiary structures of tRNA molecules might influence the efficacy of these methylations is the subject of a brief discussion. Attention is also focused on the evolutionary and molecular basis for the generally non-random distributions of methylated oligonucleotide sequences in ribosomal and transfer ribonucleates.", "contents": "Wheat embryo ribonucleates. V. Generation of N2--dimethylguanylate when 'fully sequenced' homogeneous species of transfer RNA are used as substrates for wheat embryo methyltransferases. When S-adenosly[methyl-14-C]methionine and various species of transfer RNA are used as substrates for wheat embryo methyltransferases, the principal site of guanylate-N-2 methylation can be shown to be a G-residue between the stems of the dihydrouridine and anticodon loops. This common site of guanylate-N-2 methylation is referred to as the interstem target site. 2. When the interstem target site is the non-terminal G-residue in a G-C-G-C sequence, as in the cases of Escherichia coli tRNA1-Leu, tRNA-Ile, and tRNA3-Ser, there is preponderant dimethylation to yield N-2-dimethylguanylate. 3. When the interstem target site is part of a U-C-G-U sequence, as in the case of E. coli tRNAf-Met, there is diminished dimethylation and correspondingly increased monomethylation to yield N-2-monomethylguanylate. 4. When the interstem target site is the non-terminal G-residue in an A-U-G-G sequence, as in the case of yeast tRNA-Asp, there is negligible dimethylation and almost exclusive monomethylation to yield N-2-monomethylguanylate. 5. The concerted way in which the primary, secondary, and tertiary structures of tRNA molecules might influence the efficacy of these methylations is the subject of a brief discussion. Attention is also focused on the evolutionary and molecular basis for the generally non-random distributions of methylated oligonucleotide sequences in ribosomal and transfer ribonucleates."}
{"id": "PMID:237623", "title": "Specificity of gamma-glutamyl cyclotransferase.", "content": "Using the phthaloyl method, 18 gamma-L-glutamyl peptides labelled with 14-C in the N-terminal position have been synthesized. The products were isolated by simple procedures using a Dowex-1 column or high voltage electrophoresis. The synthetic peptides contain minor impurities of the corresponding D-glutamyl isomers. The proportion of D-isomer was determined by the use of glutamic decarboxylase, or by a new method using digestion with purified gamma-glutamyl cyclotransferase and determination of the resulting 2-pyrrolidone-5-carboxylic acid (5-oxoproline). Evidence was obtained that gamma-glutamyl cyclotransferase acts only on the L-form of gamma-glutamyl substrates; the enzyme could, therefore, be used for preparation of gamma-D-glutamyl peptides from their racemic mixtures. The specificity of gamma-glutamyl cyclotransferase has been examined using pure enzyme prepared from pig liver, and extracts from tissues of rat and man. The basic structural requirement in substrates may be represented as gamma-L-glutamyl-NH--CHR--COOH. The amino acid linked to the gamma-glutamyl group must be in the L configuration.", "contents": "Specificity of gamma-glutamyl cyclotransferase. Using the phthaloyl method, 18 gamma-L-glutamyl peptides labelled with 14-C in the N-terminal position have been synthesized. The products were isolated by simple procedures using a Dowex-1 column or high voltage electrophoresis. The synthetic peptides contain minor impurities of the corresponding D-glutamyl isomers. The proportion of D-isomer was determined by the use of glutamic decarboxylase, or by a new method using digestion with purified gamma-glutamyl cyclotransferase and determination of the resulting 2-pyrrolidone-5-carboxylic acid (5-oxoproline). Evidence was obtained that gamma-glutamyl cyclotransferase acts only on the L-form of gamma-glutamyl substrates; the enzyme could, therefore, be used for preparation of gamma-D-glutamyl peptides from their racemic mixtures. The specificity of gamma-glutamyl cyclotransferase has been examined using pure enzyme prepared from pig liver, and extracts from tissues of rat and man. The basic structural requirement in substrates may be represented as gamma-L-glutamyl-NH--CHR--COOH. The amino acid linked to the gamma-glutamyl group must be in the L configuration."}
{"id": "PMID:237624", "title": "Kinetics and reaction mechanism of the carbamylphosphate synthetase of a multienzyme aggregate from yeast.", "content": "We have studied the kinetics and reaction mechanism of the carbamylphosphate synthetase of an enzyme aggregate functioning in the pyrimidine pathway of yeast. MG--ATP was found to be one of the substrates of the enzyme reaction which was activated by free Mg-2+ and inhibited by free ATP. Feedback inhibition by UTP was non-competitive with respect to both glutamine and bicarbonate. Potassium ions were essential for activity and could not be replaced by sodium. Glutamine could be replaced partially by ammonium ions as nitrogen donor. A bicarbonate-dependent cleavage of ATP was shown to take place in the absence of L-glutamine; L-glutamate was a competitive inhibitor of L-glutamine and the enzyme was shown to synthesize ATP when incubated with ADP and carbamyl phosphate. The reaction mechanism was found to involve sequential addition of the substrates bicarbonate and Mg--ATP and release of ADP, followed by addition of the third substrate glutamine. The purine nucleotide XMP had a pronounced activating effect on the enzyme, acting at a site different from that of UTP. Saturating levels of Mg--ATP eliminated this activation.", "contents": "Kinetics and reaction mechanism of the carbamylphosphate synthetase of a multienzyme aggregate from yeast. We have studied the kinetics and reaction mechanism of the carbamylphosphate synthetase of an enzyme aggregate functioning in the pyrimidine pathway of yeast. MG--ATP was found to be one of the substrates of the enzyme reaction which was activated by free Mg-2+ and inhibited by free ATP. Feedback inhibition by UTP was non-competitive with respect to both glutamine and bicarbonate. Potassium ions were essential for activity and could not be replaced by sodium. Glutamine could be replaced partially by ammonium ions as nitrogen donor. A bicarbonate-dependent cleavage of ATP was shown to take place in the absence of L-glutamine; L-glutamate was a competitive inhibitor of L-glutamine and the enzyme was shown to synthesize ATP when incubated with ADP and carbamyl phosphate. The reaction mechanism was found to involve sequential addition of the substrates bicarbonate and Mg--ATP and release of ADP, followed by addition of the third substrate glutamine. The purine nucleotide XMP had a pronounced activating effect on the enzyme, acting at a site different from that of UTP. Saturating levels of Mg--ATP eliminated this activation."}
{"id": "PMID:237625", "title": "Apparent thiamin status of cattle and its relationship to polioencephalomalacia.", "content": "The thiamin status (thiamin concentration in whole blood, plasma, and erythrocytes; erythrocyte transketolase activity) of normal cattle consuming varying diets did not differ from that of cattle with polioencephalomalacia or lead poisoning. Dairy cattle had higher ruminal content of thiamin and lower thiamin destroying activity than did beef cattle. Renal oxalosis was no more frequent in cattle which had polioencephalomalacia than in postnatal calves. In normal beef cattle, approximately 75% of total blood thiamin is in erythrocytes and the remainder in plasma.", "contents": "Apparent thiamin status of cattle and its relationship to polioencephalomalacia. The thiamin status (thiamin concentration in whole blood, plasma, and erythrocytes; erythrocyte transketolase activity) of normal cattle consuming varying diets did not differ from that of cattle with polioencephalomalacia or lead poisoning. Dairy cattle had higher ruminal content of thiamin and lower thiamin destroying activity than did beef cattle. Renal oxalosis was no more frequent in cattle which had polioencephalomalacia than in postnatal calves. In normal beef cattle, approximately 75% of total blood thiamin is in erythrocytes and the remainder in plasma."}
{"id": "PMID:237626", "title": "Exercise-induced increase in the capacity of rat skeletal muscle to oxidize ketones.", "content": "During and after strenuous prolonged exercise, sedentary individuals develop high blood levels of acetoacetate and beta-hydroxybutyrate whereas exercise-trained animals and human subjects do not. We have investigated the possibility that exercise training can increase the capacity of skeletal muscle to oxidize ketones. In this study we measured rates of D-beta[3-14-C]-hydroxybutyrate and [3-14-C]acetoacetate oxidation, and the levels of activity of the enzymes involved in the oxidation of ketones in homogenates of gastrocnemius muscles of exercise-trained and of untrained male rats. The trained animals had markedly lower blood ketone levels immediately and 60 min after a 90 min long bout of exercise than did the sedentary animals. The rates of D-beta-[13-14C]hydroxybutryate and [3-14-C]acetoacetate oxidation were twice as high in homogenates of muscles from the trained as compared to the sedentary rats. The increases in levels of activity in gastrocnemius muscle in response to the exercise program were: beta-hydroxybutyrate dehydrogenase threefold; 3-ketoacid CoA-transferase twofold; and acetoacetyl-CoA thiolase 55%. This exercise-induced increase in the capacity of skeletal muscle to oxidize ketones could play a role in preventing development of ketosis in the physically trained animal during and following prolonged strenuous exercise.", "contents": "Exercise-induced increase in the capacity of rat skeletal muscle to oxidize ketones. During and after strenuous prolonged exercise, sedentary individuals develop high blood levels of acetoacetate and beta-hydroxybutyrate whereas exercise-trained animals and human subjects do not. We have investigated the possibility that exercise training can increase the capacity of skeletal muscle to oxidize ketones. In this study we measured rates of D-beta[3-14-C]-hydroxybutyrate and [3-14-C]acetoacetate oxidation, and the levels of activity of the enzymes involved in the oxidation of ketones in homogenates of gastrocnemius muscles of exercise-trained and of untrained male rats. The trained animals had markedly lower blood ketone levels immediately and 60 min after a 90 min long bout of exercise than did the sedentary animals. The rates of D-beta-[13-14C]hydroxybutryate and [3-14-C]acetoacetate oxidation were twice as high in homogenates of muscles from the trained as compared to the sedentary rats. The increases in levels of activity in gastrocnemius muscle in response to the exercise program were: beta-hydroxybutyrate dehydrogenase threefold; 3-ketoacid CoA-transferase twofold; and acetoacetyl-CoA thiolase 55%. This exercise-induced increase in the capacity of skeletal muscle to oxidize ketones could play a role in preventing development of ketosis in the physically trained animal during and following prolonged strenuous exercise."}
{"id": "PMID:237628", "title": "Patterns of action of glucoamylase isozymes from Aspergillus species on glycogen.", "content": "Glucoamylase isozymes from black Aspergillus species have been freed of all traces of alpha-amylase by chromatography on Bio-Gel P-100, as evidenced by limited hydrolysis of oxidized amylose. Glucoamylase I retains its ability to hydrolyze rabbit-liver glycogen rapidly. By contrast, glucoamylase II hydrolyzes glycogen slowly, and addition of alpha-amylase to glucoamylase II does not enhance its activity toward glycogen. These results indicate that alpha-amylase is not involved in hydrolysis of glycogen by glucoamylase.", "contents": "Patterns of action of glucoamylase isozymes from Aspergillus species on glycogen. Glucoamylase isozymes from black Aspergillus species have been freed of all traces of alpha-amylase by chromatography on Bio-Gel P-100, as evidenced by limited hydrolysis of oxidized amylose. Glucoamylase I retains its ability to hydrolyze rabbit-liver glycogen rapidly. By contrast, glucoamylase II hydrolyzes glycogen slowly, and addition of alpha-amylase to glucoamylase II does not enhance its activity toward glycogen. These results indicate that alpha-amylase is not involved in hydrolysis of glycogen by glucoamylase."}
{"id": "PMID:237629", "title": "Purification and characterization of a glycosyltransferase complex from the culture broth of Streptococcus mutans FA1.", "content": "The extracellular glycosyltransferases from Streptococcus mutans FA1 were purified by using the following procedures: ammonium sulfate precipitation, poly-(acrylamide) gel filtration, DEAE-cellulose chromatography, and agarose-gel filtration. The dextransucrase and levansucrase activities were purified 350- and 500-fold, repsectively, and the ratio of the two activities remained almost constant throughout the purification. Both enzymes have a pH optimum of 6.0, a Km for sucrose of 55mM, and isoelectric points of 3.7 and 4.6. The enzymes are inactivated by repeated freezing and thawing, but retain partial activity even after heating at 100 degrees. The enzyme preparation contains a carbohydrate moiety which does not appear to be either bound levan or dextran.", "contents": "Purification and characterization of a glycosyltransferase complex from the culture broth of Streptococcus mutans FA1. The extracellular glycosyltransferases from Streptococcus mutans FA1 were purified by using the following procedures: ammonium sulfate precipitation, poly-(acrylamide) gel filtration, DEAE-cellulose chromatography, and agarose-gel filtration. The dextransucrase and levansucrase activities were purified 350- and 500-fold, repsectively, and the ratio of the two activities remained almost constant throughout the purification. Both enzymes have a pH optimum of 6.0, a Km for sucrose of 55mM, and isoelectric points of 3.7 and 4.6. The enzymes are inactivated by repeated freezing and thawing, but retain partial activity even after heating at 100 degrees. The enzyme preparation contains a carbohydrate moiety which does not appear to be either bound levan or dextran."}
{"id": "PMID:237631", "title": "Neural stimulation of mitotic activity in the crypts of lieberk\u00fchn in rat jejunum.", "content": "The influence of nerve stimulation and sham-stimulation on the mitotic rate in epithelial cells lining the crypts of Lieberk\u00fchn in the jejunum of anaesthetized rats was studied. Administration of the anaesthetic and opening the abdominal cavity was without significant effect on the crypt cell mitotic rate. However, externalizing a loop of jejunum and applying sham-stimuli to its mesenteric nerves resulted in a significant decrease in the crypt cell mitotic rate in that loop. Application of electrical stimuli to the mesenteric nerves of another externalized jejunal loop resulted in a significant increase in the mitotic rate in the crypt cells of that segment. Similar acceleration of crypt cell proliferation by electrical stimuli applied to mesenteric nerves was also seen in chemically sympathectomized rats.", "contents": "Neural stimulation of mitotic activity in the crypts of lieberk\u00fchn in rat jejunum. The influence of nerve stimulation and sham-stimulation on the mitotic rate in epithelial cells lining the crypts of Lieberk\u00fchn in the jejunum of anaesthetized rats was studied. Administration of the anaesthetic and opening the abdominal cavity was without significant effect on the crypt cell mitotic rate. However, externalizing a loop of jejunum and applying sham-stimuli to its mesenteric nerves resulted in a significant decrease in the crypt cell mitotic rate in that loop. Application of electrical stimuli to the mesenteric nerves of another externalized jejunal loop resulted in a significant increase in the mitotic rate in the crypt cells of that segment. Similar acceleration of crypt cell proliferation by electrical stimuli applied to mesenteric nerves was also seen in chemically sympathectomized rats."}
{"id": "PMID:237636", "title": "Toxicological implications of the mixed-function oxidase catalyzed metabolism of carbon disulfide.", "content": "The results of these studies have indicated that the decrease in the activity of the hepatic mixed-function oxidase enzyme system and the concentration of cytochrome P-450 seen on incubation of carbon disulfide (CS2) with rat liver microsomes in the presence of NADPH is the result of the binding of the sulfur atom released in the mixed-function oxidase catalyzed metabolism of CS2 to carbonyl sulfide (COS). Moreover, it appears that COS is further metabolized by the mixed-function oxidase enzyme system to CO2 and that, analogous to the metabolism of CS2 to COS, the sulfur atom released in this reaction also binds to the microsomes and inhibits benzphetamine metabolism and decreases the concentration of cytochrome P-450 detectable as its carbon monoxide complex. The results of these studies also suggest that the decrease in the concentration of cytochrome P-450 and the liver damage seen on in vivo administration of CS2 to phenobarbital pretreated rats, is due to the mixed-function oxidase catalyzed release and binding of the sulfur atoms of CS2. The decrease in the concentration of cytochrome P-450 seen on incubation of CS2 with rat liver microsomes in the presence of NADPH  does not appear to be the result of destruction of the heme group or its dissociation from the apoenzyme since the total amount of protoheme is unchanged in microsomes which have been incubated with CS2 and NADPH as compared to those not incubated with these compounds.", "contents": "Toxicological implications of the mixed-function oxidase catalyzed metabolism of carbon disulfide. The results of these studies have indicated that the decrease in the activity of the hepatic mixed-function oxidase enzyme system and the concentration of cytochrome P-450 seen on incubation of carbon disulfide (CS2) with rat liver microsomes in the presence of NADPH is the result of the binding of the sulfur atom released in the mixed-function oxidase catalyzed metabolism of CS2 to carbonyl sulfide (COS). Moreover, it appears that COS is further metabolized by the mixed-function oxidase enzyme system to CO2 and that, analogous to the metabolism of CS2 to COS, the sulfur atom released in this reaction also binds to the microsomes and inhibits benzphetamine metabolism and decreases the concentration of cytochrome P-450 detectable as its carbon monoxide complex. The results of these studies also suggest that the decrease in the concentration of cytochrome P-450 and the liver damage seen on in vivo administration of CS2 to phenobarbital pretreated rats, is due to the mixed-function oxidase catalyzed release and binding of the sulfur atoms of CS2. The decrease in the concentration of cytochrome P-450 seen on incubation of CS2 with rat liver microsomes in the presence of NADPH  does not appear to be the result of destruction of the heme group or its dissociation from the apoenzyme since the total amount of protoheme is unchanged in microsomes which have been incubated with CS2 and NADPH as compared to those not incubated with these compounds."}
{"id": "PMID:237638", "title": "The assay of pyruvate kinase activity in gastric mucosa.", "content": "Pyruvate kinase activity in gastric mucosal supernatant preparations shows large responses to exogenous effectors. At pH 7.5, fructose 1,6-diphosphate can cause large stimulations in activity. Alanine inhibits the reaction but this effect is partially reversed by fructose 1,6-diphosphate. In the absence of these compounds, 4.0-5.0 mM phosphoenolpyruvate (PEP) is required to generate maximal activity in the assay system used. Electrophoresis reveals an isoenzyme pattern containing only one form of pyruvate kinase, an M isoenzyme, in both fundic and antral mucosa. The pyruvate kinase of gastric mucosa thus resembles the M-type enzymes of leucocytes and liver. Measurements of activity at both 1.0 mM PEP and 4.0--5.0 mM PEP, with and without additions of fructose 1,6-diphosphate, are recommended for the reliable estimation of pyruvate kinase activity in this tissue.", "contents": "The assay of pyruvate kinase activity in gastric mucosa. Pyruvate kinase activity in gastric mucosal supernatant preparations shows large responses to exogenous effectors. At pH 7.5, fructose 1,6-diphosphate can cause large stimulations in activity. Alanine inhibits the reaction but this effect is partially reversed by fructose 1,6-diphosphate. In the absence of these compounds, 4.0-5.0 mM phosphoenolpyruvate (PEP) is required to generate maximal activity in the assay system used. Electrophoresis reveals an isoenzyme pattern containing only one form of pyruvate kinase, an M isoenzyme, in both fundic and antral mucosa. The pyruvate kinase of gastric mucosa thus resembles the M-type enzymes of leucocytes and liver. Measurements of activity at both 1.0 mM PEP and 4.0--5.0 mM PEP, with and without additions of fructose 1,6-diphosphate, are recommended for the reliable estimation of pyruvate kinase activity in this tissue."}
{"id": "PMID:237639", "title": "The radiometric assay of alkaline phosphatase activity with 125-I-labelled phenolphthalein monophosphate.", "content": "The coupling of 125-I to phenolphthalein monophosphate is described. Hydrolytic cleavage of the phosphate group by alkaline phosphatases (EC 3.1.-3.1) releases labelled phenolphthalein which is extracted into ethyl acetate at pH 10. This forms the basis of a sensitive assay for the enzyme with the advantages of sensitivity and rapidity from the use of a gamma-emitter. Results with Escherichia coli and calf intestine alkaline phosphatases are presented.", "contents": "The radiometric assay of alkaline phosphatase activity with 125-I-labelled phenolphthalein monophosphate. The coupling of 125-I to phenolphthalein monophosphate is described. Hydrolytic cleavage of the phosphate group by alkaline phosphatases (EC 3.1.-3.1) releases labelled phenolphthalein which is extracted into ethyl acetate at pH 10. This forms the basis of a sensitive assay for the enzyme with the advantages of sensitivity and rapidity from the use of a gamma-emitter. Results with Escherichia coli and calf intestine alkaline phosphatases are presented."}
{"id": "PMID:237643", "title": "Amino acid metabolism in the chronically uremic rat.", "content": "The chronically uremic rat has been used as a model to study amino acid metabolism in uremia. Uremic rats fed low protein diets (6% casein) survived longer than uremic rats receiving either higher levels of dietary protein or a low protein diet supplemented with a mixture of nonessential amino acids. Alterations in plasma amino acid levels were observed in the uremic rats and were similar to those found in patients with renal failure. Plasma concentrations of citrulline, free tryptophan, glycine and the methylhistidines were increased and levels of serine, ornithine, lysine, total tryptophan, tyrosine, and the tyrosine-phenylalanine ratio were reduced. The metabolic basis of the altered tyrosine-phenylalanine ratio in plasma was studied. Tyrosine aminotransferase (TAT) and phenylalanine hydroxylase (PHL) activity were normal in the liver, but renal PHL activity of was decreased as compared to control rats. Tissue concentrations of citrulline were also found to be raised in liver and muscle of uremic rats. The activity of ornithine transcarbamoylase, was reduced in the liver and arginine synthetase activity was decreased in the kidneys of uremic rats. Thus elevated citrulline levels in uremic tissue appear to be caused by a decrease conversion of citrulline to arginine in the kidney. Preliminary studies of tryptophan metabolism in uremic rats have shown elevated brain levels of 5-hydroxyindoleacetic acid and increased hepatic tryptophan oxygenase activity. Increased plasma amine levels were associated with altered activities of monoamine oxidase and diamine oxidase in kidney and other tissues.", "contents": "Amino acid metabolism in the chronically uremic rat. The chronically uremic rat has been used as a model to study amino acid metabolism in uremia. Uremic rats fed low protein diets (6% casein) survived longer than uremic rats receiving either higher levels of dietary protein or a low protein diet supplemented with a mixture of nonessential amino acids. Alterations in plasma amino acid levels were observed in the uremic rats and were similar to those found in patients with renal failure. Plasma concentrations of citrulline, free tryptophan, glycine and the methylhistidines were increased and levels of serine, ornithine, lysine, total tryptophan, tyrosine, and the tyrosine-phenylalanine ratio were reduced. The metabolic basis of the altered tyrosine-phenylalanine ratio in plasma was studied. Tyrosine aminotransferase (TAT) and phenylalanine hydroxylase (PHL) activity were normal in the liver, but renal PHL activity of was decreased as compared to control rats. Tissue concentrations of citrulline were also found to be raised in liver and muscle of uremic rats. The activity of ornithine transcarbamoylase, was reduced in the liver and arginine synthetase activity was decreased in the kidneys of uremic rats. Thus elevated citrulline levels in uremic tissue appear to be caused by a decrease conversion of citrulline to arginine in the kidney. Preliminary studies of tryptophan metabolism in uremic rats have shown elevated brain levels of 5-hydroxyindoleacetic acid and increased hepatic tryptophan oxygenase activity. Increased plasma amine levels were associated with altered activities of monoamine oxidase and diamine oxidase in kidney and other tissues."}
{"id": "PMID:237640", "title": "The effects of 2-thiophenecarboxylic acid on serum ionic calcium and magnesium levels in rats.", "content": "1. Administration of 2-thiophenecarboxylic acid to rats maintained on a low calcium diet resulted in a significant depression in the serum levels of total and ionized calcium and inorganic phosphate. 2. The serum magnesium levels were not altered by the drug.", "contents": "The effects of 2-thiophenecarboxylic acid on serum ionic calcium and magnesium levels in rats. 1. Administration of 2-thiophenecarboxylic acid to rats maintained on a low calcium diet resulted in a significant depression in the serum levels of total and ionized calcium and inorganic phosphate. 2. The serum magnesium levels were not altered by the drug."}
{"id": "PMID:237641", "title": "Some actions of chandonium iodide, a new short-acting muscle relaxant, in anaesthetized cats and on isolated muscle preparations.", "content": "1. The actions of the new skeletal muscle relaxant chandonium (HS310) on the cardiovascular, respiratory and skeletal muscle systems of the cat under chloralose anaesthesia and on chick and rat isolated skeletal muscle preparations have been described. 2. In the cat chandonium exhibited a potent, competitive, non-depolarizing neuromuscular blocking action that was rapid in onset and of short duration. It possessed a selective atropine-like action at the cardiac vagus neuro-effector junction but little or no ganglion blocking activity. Neither adrenergic neurone noralpha-adrenoceptor blocking properties were evident. 3. Unlike tubocurarine, chandonium was without effect on the airways system of the anaesthetized cat. 4. Chandonium possessed weak anticholinesterase action. It is conceivable that this effect may contribute to its short duration of action. 5. The results from these studies suggest that chandonium may have possible clinical applications as a short-acting muscle relaxant.", "contents": "Some actions of chandonium iodide, a new short-acting muscle relaxant, in anaesthetized cats and on isolated muscle preparations. 1. The actions of the new skeletal muscle relaxant chandonium (HS310) on the cardiovascular, respiratory and skeletal muscle systems of the cat under chloralose anaesthesia and on chick and rat isolated skeletal muscle preparations have been described. 2. In the cat chandonium exhibited a potent, competitive, non-depolarizing neuromuscular blocking action that was rapid in onset and of short duration. It possessed a selective atropine-like action at the cardiac vagus neuro-effector junction but little or no ganglion blocking activity. Neither adrenergic neurone noralpha-adrenoceptor blocking properties were evident. 3. Unlike tubocurarine, chandonium was without effect on the airways system of the anaesthetized cat. 4. Chandonium possessed weak anticholinesterase action. It is conceivable that this effect may contribute to its short duration of action. 5. The results from these studies suggest that chandonium may have possible clinical applications as a short-acting muscle relaxant."}
{"id": "PMID:237645", "title": "Thromboembolic complications of cast immobilization for injuries of the lower extremities.", "content": "Six cases of thromboembolic complications in patients being treated with plaster cast immobilization for a variety of injuries to the lower extremity were encountered over a four month period on an Air Force orthopaedic service. These injuries, consisting of three ruptures of the tendo achillis, two fractures of the tibia, and a sub-talar dislocation of the foot, resulted in one death from pulmonary emboli and three other serious complications of pulmonary emboli. The literature on thromboembolic complications following lower extremity injuries (including information of pathogenesis, clinical characteristics and epidemiology of venous thromboembolism and the hazards of lowere extremity cast immobilization in an individual susceptible to his complication) suggests that prophylaxis against thrombosis should be instituted in high risk individuals who must undergo case immobilization for injuries to the lower extremity.", "contents": "Thromboembolic complications of cast immobilization for injuries of the lower extremities. Six cases of thromboembolic complications in patients being treated with plaster cast immobilization for a variety of injuries to the lower extremity were encountered over a four month period on an Air Force orthopaedic service. These injuries, consisting of three ruptures of the tendo achillis, two fractures of the tibia, and a sub-talar dislocation of the foot, resulted in one death from pulmonary emboli and three other serious complications of pulmonary emboli. The literature on thromboembolic complications following lower extremity injuries (including information of pathogenesis, clinical characteristics and epidemiology of venous thromboembolism and the hazards of lowere extremity cast immobilization in an individual susceptible to his complication) suggests that prophylaxis against thrombosis should be instituted in high risk individuals who must undergo case immobilization for injuries to the lower extremity."}
{"id": "PMID:237647", "title": "Polymorphic acetylation procainamide in man.", "content": "N-Acetylprocainamide (NAPA) and procainamide plasma and urine concentrations were determined by thin-layer chromatography (TLC) densitometry in people of known acetylator phenotype (dapsone phenotyping) taking procainamide for more than 3 days. The plasma NAPA/procainamide ratio 3 hr after the last dose for fast acetylators (mean plus or minus SD) is 1.8 plus or minus 0.59 (N equal to 8) and for slow acetylators, 0.61 plus or minus 0.09 (N equal to 6) P smaller than 0.001). The renal clearance of NAPA averaged 1.2 times the simultaneously measured endogenous creatinine clearance, whereas procainamide clearance was approximately double the creatinine clearance. There was no difference between slow and rapid acetylators in the renal clearance of either drug or the urine pH, indicating that the difference in plasma NAPA/procainamide ratios between these two groups is due to differences in their rates of acetylation. Therefore, procainamide is probably acetylated by the polymorphic N-acetyltransferase in man. Reflecting the blood level differences, the NAPA/procainamide ratio in urine (collected 99 to 180 min after last dose) was found to be higher in rapid than in slow acetylators. The plasma protein binding of NAa and of procainamide are similar. Since NAPA seems to have an antiarrhythmic potency similar to procainamide, NAPA probably contributes to the antiarrhythmic activity of procainamide therapy, especially in genetic rapid acetylators.", "contents": "Polymorphic acetylation procainamide in man. N-Acetylprocainamide (NAPA) and procainamide plasma and urine concentrations were determined by thin-layer chromatography (TLC) densitometry in people of known acetylator phenotype (dapsone phenotyping) taking procainamide for more than 3 days. The plasma NAPA/procainamide ratio 3 hr after the last dose for fast acetylators (mean plus or minus SD) is 1.8 plus or minus 0.59 (N equal to 8) and for slow acetylators, 0.61 plus or minus 0.09 (N equal to 6) P smaller than 0.001). The renal clearance of NAPA averaged 1.2 times the simultaneously measured endogenous creatinine clearance, whereas procainamide clearance was approximately double the creatinine clearance. There was no difference between slow and rapid acetylators in the renal clearance of either drug or the urine pH, indicating that the difference in plasma NAPA/procainamide ratios between these two groups is due to differences in their rates of acetylation. Therefore, procainamide is probably acetylated by the polymorphic N-acetyltransferase in man. Reflecting the blood level differences, the NAPA/procainamide ratio in urine (collected 99 to 180 min after last dose) was found to be higher in rapid than in slow acetylators. The plasma protein binding of NAa and of procainamide are similar. Since NAPA seems to have an antiarrhythmic potency similar to procainamide, NAPA probably contributes to the antiarrhythmic activity of procainamide therapy, especially in genetic rapid acetylators."}
{"id": "PMID:237648", "title": "Changes in protein-bound calcium in the serum of haemodialysis patients.", "content": "1. Ionized calcium, protein-bound calcium and total calcium in serum were measured in patients receiving haemodialysis treatment. 2. During dialysis, the ionized calcium fraction decreased and the bound calcium increased. The blood pH also increased. 3. Studies in vitro suggested that the fall in ionized calcium and rise in protein-bound calcium were larger than could be explained by the redistribution of calcium fractions due to the pH change. 4. An explanation could be that haemodialysis increases calcium binding by serum proteins. Such an effect may be implicated in the aetiology of hyperparathyroidism and bone disease in patients undergoing haemodialysis.", "contents": "Changes in protein-bound calcium in the serum of haemodialysis patients. 1. Ionized calcium, protein-bound calcium and total calcium in serum were measured in patients receiving haemodialysis treatment. 2. During dialysis, the ionized calcium fraction decreased and the bound calcium increased. The blood pH also increased. 3. Studies in vitro suggested that the fall in ionized calcium and rise in protein-bound calcium were larger than could be explained by the redistribution of calcium fractions due to the pH change. 4. An explanation could be that haemodialysis increases calcium binding by serum proteins. Such an effect may be implicated in the aetiology of hyperparathyroidism and bone disease in patients undergoing haemodialysis."}
{"id": "PMID:237736", "title": "The neurologic effects of noxious marine creatures.", "content": "The concept of the sea as a source of noxious agents is perhaps not a familiar one to clinical neurologists, judging by the lack of reference to these agents in standard textbooks. Chemical, physiologic, and pharmacologic laboratories are increasingly investigating the properties of marine toxins, finding in them compounds with interesting and novel structures or unusual physiologic effects. Such substances are seen as possible agents for biologic and, more particularly, physiologic research, and as possible sources of new pharmaceuticals. These include hormone-like substances and antiviral or antitumor agents. Despite these specialized developments, which are in large measure a consequence of the technological advances of the present century, the clinician is at times directly concerned with the effects of marine toxic substances. For example, in Japan, puffer fish or tetrodotoxic poisoning is one of the major causes of deaths from food poisoning. Another marine toxin that has caused many explosive outbreaks of food poisoning. with many deaths in various parts of the world, comes from clams or mussels. This toxin, saxitoxin, is produced by species of marine protozoa including Gonyaulax, and is concentrated in filter-feeding molluscs. These two examples were of significant interest in medicine long before the technologic developments of the twentieth century. In the last few decades, entirely new problems of marine intoxication have arisen as a result of marine pollution from the disposal of industrial wastes in the sea. The most striking example of a man-made marine intoxication has been the outbreak of Minamata disease. In Minamata, Japan, the disposal of mercury-contaminated industrial wastes from a plastics factory into an enclosed bay, followed by human consumption of the contaminated fishes, crabs, or shellfish, led to many instances of acute cerebral degeneration. With the increasing exploration of the sea for both pleasure and economic exploitation, which is a feature of the second half of the twentieth century, it may be expected that the frequency and variety of human intoxications by marine creatures will be increased. This chapter reviews the neurologic effects of noxious substances of marine biologic origin. The subject is now developing so rapidly that overall surveys, such as this, of the general animal life of theocens will soon be beyond the scope of a single review. Nevertheless, it is hoped that the references given will enable the interested reader to pursue particular aspects further.", "contents": "The neurologic effects of noxious marine creatures. The concept of the sea as a source of noxious agents is perhaps not a familiar one to clinical neurologists, judging by the lack of reference to these agents in standard textbooks. Chemical, physiologic, and pharmacologic laboratories are increasingly investigating the properties of marine toxins, finding in them compounds with interesting and novel structures or unusual physiologic effects. Such substances are seen as possible agents for biologic and, more particularly, physiologic research, and as possible sources of new pharmaceuticals. These include hormone-like substances and antiviral or antitumor agents. Despite these specialized developments, which are in large measure a consequence of the technological advances of the present century, the clinician is at times directly concerned with the effects of marine toxic substances. For example, in Japan, puffer fish or tetrodotoxic poisoning is one of the major causes of deaths from food poisoning. Another marine toxin that has caused many explosive outbreaks of food poisoning. with many deaths in various parts of the world, comes from clams or mussels. This toxin, saxitoxin, is produced by species of marine protozoa including Gonyaulax, and is concentrated in filter-feeding molluscs. These two examples were of significant interest in medicine long before the technologic developments of the twentieth century. In the last few decades, entirely new problems of marine intoxication have arisen as a result of marine pollution from the disposal of industrial wastes in the sea. The most striking example of a man-made marine intoxication has been the outbreak of Minamata disease. In Minamata, Japan, the disposal of mercury-contaminated industrial wastes from a plastics factory into an enclosed bay, followed by human consumption of the contaminated fishes, crabs, or shellfish, led to many instances of acute cerebral degeneration. With the increasing exploration of the sea for both pleasure and economic exploitation, which is a feature of the second half of the twentieth century, it may be expected that the frequency and variety of human intoxications by marine creatures will be increased. This chapter reviews the neurologic effects of noxious substances of marine biologic origin. The subject is now developing so rapidly that overall surveys, such as this, of the general animal life of theocens will soon be beyond the scope of a single review. Nevertheless, it is hoped that the references given will enable the interested reader to pursue particular aspects further."}
{"id": "PMID:237740", "title": "Human leptospirosis.", "content": "Human leptospirosis is a subject of increasing interest. Although this disease was frequently associated with individuals whose occupation or geographic location placed them in close proximity to wild animals or farm animals, recent cases have been particularly prevalent in young children and adolescents in urban and suburban America. Many of the recent cases have been acquired from household pets, particularly from dogs or hamsters. In particular, healthy dogs who have been immunized with leptospiral organisms, thereby creating a significant risk for their owners. This article will review the pathophysiology, clincal manifestations, laboratory diagnosis, treatment, and prevention of leptospirosis in the modern era, with particular emphasis on a more complete understanding of the epidemiology of this disorder.", "contents": "Human leptospirosis. Human leptospirosis is a subject of increasing interest. Although this disease was frequently associated with individuals whose occupation or geographic location placed them in close proximity to wild animals or farm animals, recent cases have been particularly prevalent in young children and adolescents in urban and suburban America. Many of the recent cases have been acquired from household pets, particularly from dogs or hamsters. In particular, healthy dogs who have been immunized with leptospiral organisms, thereby creating a significant risk for their owners. This article will review the pathophysiology, clincal manifestations, laboratory diagnosis, treatment, and prevention of leptospirosis in the modern era, with particular emphasis on a more complete understanding of the epidemiology of this disorder."}
{"id": "PMID:237743", "title": "Alteration of Ringer pH and its effects on precursor incorporation into Drosophila salivary gland nuclei.", "content": "Drosophila salivary glands were explanted and incubated with 3-H-uridine (or 3-H-thymidine) in Ringer's solution (Ephrussi-Beadle modified saline) adjusted to pH values in the integral range, 4 to 10. The results of autoradiographic investigations indicate a differential effect of altering Ringer pH on 3-H-uridine as opposed to 3-H-thymidine incorporation: a) Relatively uniform levels of chromosomal incorporation of 3-H-thymidine occured over the range of test pH. Some decrease of incorporation was noted at pH 5 and some increase at pH 9. b) Chromosomal incoroporation of 3H-uridine was severely depressed at pH 4 and 7 relative to the high incorporation levels observed at other pH values. Controlling pH of Ephrussi-Beadle Ringer's solution in such experiments a necessity. This appears especially important for studies involving 3-H-uridine incorporation.", "contents": "Alteration of Ringer pH and its effects on precursor incorporation into Drosophila salivary gland nuclei. Drosophila salivary glands were explanted and incubated with 3-H-uridine (or 3-H-thymidine) in Ringer's solution (Ephrussi-Beadle modified saline) adjusted to pH values in the integral range, 4 to 10. The results of autoradiographic investigations indicate a differential effect of altering Ringer pH on 3-H-uridine as opposed to 3-H-thymidine incorporation: a) Relatively uniform levels of chromosomal incorporation of 3-H-thymidine occured over the range of test pH. Some decrease of incorporation was noted at pH 5 and some increase at pH 9. b) Chromosomal incoroporation of 3H-uridine was severely depressed at pH 4 and 7 relative to the high incorporation levels observed at other pH values. Controlling pH of Ephrussi-Beadle Ringer's solution in such experiments a necessity. This appears especially important for studies involving 3-H-uridine incorporation."}
{"id": "PMID:237748", "title": "[The effect of aspirin, antacids, alcohol, and bile acids on transmural potential difference of the human stomach (author's transl)].", "content": "The effect of orally administered buffered and unbuffered aspirin, antacids, alcohol and bile salts on functional changes in the gastric mucosal barrier was assessed by measuring gastric transmural potential differences (PD) in healthy subjects. In contrast to buffered aspirin, unbuffered aspirin caused a marked decrease in transmural PD due to its known effect of enhancing H+ back-diffusion. Simultaneous administration of antacids prevented the aspirin-induced drop of transmural PD. Ethanol (20% w/v), whisky (45% w/v), wine (6-7% ethanol), bile salts and ox-bile reduced transmural PD in healthy subjects. The measurement of transmural PD is a simple and sensitive method for detecting functional changes in the gastric mucosal barrier induced by drugs known to alter mucosal permeability.", "contents": "[The effect of aspirin, antacids, alcohol, and bile acids on transmural potential difference of the human stomach (author's transl)]. The effect of orally administered buffered and unbuffered aspirin, antacids, alcohol and bile salts on functional changes in the gastric mucosal barrier was assessed by measuring gastric transmural potential differences (PD) in healthy subjects. In contrast to buffered aspirin, unbuffered aspirin caused a marked decrease in transmural PD due to its known effect of enhancing H+ back-diffusion. Simultaneous administration of antacids prevented the aspirin-induced drop of transmural PD. Ethanol (20% w/v), whisky (45% w/v), wine (6-7% ethanol), bile salts and ox-bile reduced transmural PD in healthy subjects. The measurement of transmural PD is a simple and sensitive method for detecting functional changes in the gastric mucosal barrier induced by drugs known to alter mucosal permeability."}
{"id": "PMID:237752", "title": "Generation of hypophysiotropic activity in hypothalamic extracts in vitro.", "content": "The luteinizing hormone (LH) and follicle stimulating hormone (FSH) releasing activity, as well as the prolactin (PRL) release-inhibiting activity were measured in both neutral aqueous, and acid ethanolic extracts of rat hypothalami. LH and FSH-releasing activities were detectable only in the latter type of extract, whereas PRL release-inhibiting activity appeared in both. Neutral ultrafiltrates of the neutral extracts contained no gonadotropin releasing activity, however, acidification of the filtration medium induced its appearance. PRL release was inhibited by both neutral and acid filtrates. These results suggest that LH and FSH releasing factor(s) may be stored in the hypothalamus in an inactive form from which the active peptide is generated in vitro under acid conditions; however, this does not appear to be true for the component(s) responsible for the inhibition of PRL release.", "contents": "Generation of hypophysiotropic activity in hypothalamic extracts in vitro. The luteinizing hormone (LH) and follicle stimulating hormone (FSH) releasing activity, as well as the prolactin (PRL) release-inhibiting activity were measured in both neutral aqueous, and acid ethanolic extracts of rat hypothalami. LH and FSH-releasing activities were detectable only in the latter type of extract, whereas PRL release-inhibiting activity appeared in both. Neutral ultrafiltrates of the neutral extracts contained no gonadotropin releasing activity, however, acidification of the filtration medium induced its appearance. PRL release was inhibited by both neutral and acid filtrates. These results suggest that LH and FSH releasing factor(s) may be stored in the hypothalamus in an inactive form from which the active peptide is generated in vitro under acid conditions; however, this does not appear to be true for the component(s) responsible for the inhibition of PRL release."}
{"id": "PMID:237753", "title": "Guanyl cyclase activity of human blood lymphocytes.", "content": "An enzyme, guanyl cyclase, which catalyzes formation of CYCLIC 3',5'-GMP from 5'-GTP, has been identified in human peripheral lymphocytes. The activity in lymphocyte homogenate is  14 pmol (min 10-7 lymphocytes). No activity is detected in red blood cells, and the amount found in platelets is very low. The properties of this enzyme are very close to those reported for other guanyl cyclases studied in other tissues: namely, its intracellular localization, its requirement for cation Mn-2+, its inhibition by Hg-2+, Zn-2+ and by nucleotides especially 5'-ATP. No change in enzyme activity occurs when phytohemagglutinin P is added to disrupted lymphocytes. However, when the mitogen is incubated with intact cells, guanyl cyclase activity increases in a few minutes.", "contents": "Guanyl cyclase activity of human blood lymphocytes. An enzyme, guanyl cyclase, which catalyzes formation of CYCLIC 3',5'-GMP from 5'-GTP, has been identified in human peripheral lymphocytes. The activity in lymphocyte homogenate is  14 pmol (min 10-7 lymphocytes). No activity is detected in red blood cells, and the amount found in platelets is very low. The properties of this enzyme are very close to those reported for other guanyl cyclases studied in other tissues: namely, its intracellular localization, its requirement for cation Mn-2+, its inhibition by Hg-2+, Zn-2+ and by nucleotides especially 5'-ATP. No change in enzyme activity occurs when phytohemagglutinin P is added to disrupted lymphocytes. However, when the mitogen is incubated with intact cells, guanyl cyclase activity increases in a few minutes."}
{"id": "PMID:237754", "title": "Glutamine-dependent asparagine synthetase in fetal, adult and neoplastic rat tissues.", "content": "Three enzyme reactions related to asparagine synthesis were studied in rat tissues: formation of aspartylhydroxamate, either from aspartate or by transfer from asparagine, and actual synthesis of asparagine from aspartate. Actual asparagine synthesis occurred at one-thousandth the rate of the other two reactions.  Optimal conditions for quantitative assay of asparagine synthesis were determined in fetal liver extract, which is a rich source of the enzyme. Demonstrable activity in liver fell 6 days after birth to 20% of the fetal value and decreased slowly thereafter to the low adult value.  Adult pancreas was the most active tissue found.  The asparagine synthetase of fetal liver extracts was significantly inhibited when combined with adult liver or tumor extracts. The inhibitor fractionated with ammonium sulfate in close association with the asparagine synthetase.  Therefore, demonstrable activities of asparagine synthetase in tissue extracts, measured in the presence of this inhibitor, do not necessarily parallel the concentrations of the enzyme present.", "contents": "Glutamine-dependent asparagine synthetase in fetal, adult and neoplastic rat tissues. Three enzyme reactions related to asparagine synthesis were studied in rat tissues: formation of aspartylhydroxamate, either from aspartate or by transfer from asparagine, and actual synthesis of asparagine from aspartate. Actual asparagine synthesis occurred at one-thousandth the rate of the other two reactions.  Optimal conditions for quantitative assay of asparagine synthesis were determined in fetal liver extract, which is a rich source of the enzyme. Demonstrable activity in liver fell 6 days after birth to 20% of the fetal value and decreased slowly thereafter to the low adult value.  Adult pancreas was the most active tissue found.  The asparagine synthetase of fetal liver extracts was significantly inhibited when combined with adult liver or tumor extracts. The inhibitor fractionated with ammonium sulfate in close association with the asparagine synthetase.  Therefore, demonstrable activities of asparagine synthetase in tissue extracts, measured in the presence of this inhibitor, do not necessarily parallel the concentrations of the enzyme present."}
{"id": "PMID:237755", "title": "Relationship between steroids and pyridine nucleotides in the oxido-reduction catalyzed by the 17 beta-hydroxysteroid dehydrogenase purified from the porcine testicular microsomal fraction.", "content": "The 17 beta-hydroxysteroid dehydrogenase which was purified from porcine testicular microsomal fraction [Inano, H. and Tamaoki, B (1974) Eur. J. Biochem. 44, 13-23] catalyzed the reduction of androstenedione to testosterone with the accompanying oxidation of equimolar NADPH. For the oxido-reduction of the steroids, the 17 beta-hydroxysteroid dehydrogenase preferred NADP(H) to NAD(h). Transhydrogenation from NADPH to NAD+ or NADH to NADP+ through the cyclic oxido-reduction of the steroids by the purified 17 beta hydroxysteroid dehydrogenase preparation was not spectrophotometrically detectable, because of selective preference of the testicular 17 beta-hydroxysteroid dehydrogenase against NADP(H). To examine stereospecific transfer of the hydrogen from NADPH to androstenedione by the purified 17 beta-hydroxysteroid dehydrogenase, the following tritiated cofactors were synthesized: [4-3-H]NADP+ was prepared by catalytic replacement from non-radioactive NADP+ and 3H2O in the presence of potassium cyanide. Then, [4-pro-R3H]NADPH was enzymatically synthesized from the [4-3H]NADP+ by glucose 6-phosphate and its dehydrogenase. On the other hand, [4-pro-S-3H]NADPH was prepared from the [4-3H]NADP+ by isocitrate and isocitrate dehydrogenase. When androstenedione was incubated with the 17 beta-hydroxysteroid dehydrogenase in the presence of these stereospecifically 3H-labeled cofactors, only the tritium located at 4-pro-S position of the nicotinamide moiety of NADPH was transferred to testosterone. The location of the tritium in the testosterone molecule produced, 17alpha-position of the steroid, was assigned by the fact that the tritium of the testosterone remained in its molecule after acetylation, but was completely lost by oxidation.", "contents": "Relationship between steroids and pyridine nucleotides in the oxido-reduction catalyzed by the 17 beta-hydroxysteroid dehydrogenase purified from the porcine testicular microsomal fraction. The 17 beta-hydroxysteroid dehydrogenase which was purified from porcine testicular microsomal fraction [Inano, H. and Tamaoki, B (1974) Eur. J. Biochem. 44, 13-23] catalyzed the reduction of androstenedione to testosterone with the accompanying oxidation of equimolar NADPH. For the oxido-reduction of the steroids, the 17 beta-hydroxysteroid dehydrogenase preferred NADP(H) to NAD(h). Transhydrogenation from NADPH to NAD+ or NADH to NADP+ through the cyclic oxido-reduction of the steroids by the purified 17 beta hydroxysteroid dehydrogenase preparation was not spectrophotometrically detectable, because of selective preference of the testicular 17 beta-hydroxysteroid dehydrogenase against NADP(H). To examine stereospecific transfer of the hydrogen from NADPH to androstenedione by the purified 17 beta-hydroxysteroid dehydrogenase, the following tritiated cofactors were synthesized: [4-3-H]NADP+ was prepared by catalytic replacement from non-radioactive NADP+ and 3H2O in the presence of potassium cyanide. Then, [4-pro-R3H]NADPH was enzymatically synthesized from the [4-3H]NADP+ by glucose 6-phosphate and its dehydrogenase. On the other hand, [4-pro-S-3H]NADPH was prepared from the [4-3H]NADP+ by isocitrate and isocitrate dehydrogenase. When androstenedione was incubated with the 17 beta-hydroxysteroid dehydrogenase in the presence of these stereospecifically 3H-labeled cofactors, only the tritium located at 4-pro-S position of the nicotinamide moiety of NADPH was transferred to testosterone. The location of the tritium in the testosterone molecule produced, 17alpha-position of the steroid, was assigned by the fact that the tritium of the testosterone remained in its molecule after acetylation, but was completely lost by oxidation."}
{"id": "PMID:237756", "title": "Inactivation of glyoxalase I from porcine erythrocytes and yeast by amino-group reagents.", "content": "Glyoxalase I from porcine erythrocytes and from yeast is inactivated by the amino-group reagents 1-fluoro-2,4-dinitrobenzene, 5-dimethylaminonaphthalene-1-sulfonyl chloride, and 2,4,6-trinitrobenzenesulfonate (N-3ph-S). The inactivation follows pseudo-first-order kinetics, and the apparent first-order rate constant increases with pH, indicating that the basic form of a nucleophilic group is modified. The effect of increasing the inactivator concentration was tested with N-3PH-S, and it was found that the apparent rate constant increased to a limiting value. Such a result is consistent with a mechanism involving formation of a reversible inactivator x enzyme complex prior to the actual inactivation. Experiments with erythrocyte glyoxalase I and a variety of sulfhydryl-group reagents failed to show a dependence on sulfhydryl groups for catalytic activity, in contrast to previous results with the yeast enzyme. These experiments seem to exclude the possibility that essential sulfhydryl groups of the erythrocyte enzyme are modified by the amino-group reagents. Failure of reactivation of yeast glyoxalase I, and the similarities with the erythrocyte enzyme suggest that yeast glyoxalase I is not modified at essential sulfhydryl groups either by the latter reagents. This assumption has further support from experiments involving simultaneous inactivation with amino and sulfhydryl-group reagents. The results are consistent with the interpretation that amino groups of glyoxalase I are essential for catalytic activity. Glutathione derivatives, which are reversible competitive inhibitors of glyoxalase I, were found to protect the enzyme against inactivation by amino-group reagents. However, the concentration required for half-maximal protection was considerably higher than the inhibition constant of the reversible inhibition, which indicates that at least two molecules of the protector must be bound to the enzyme before full protection is obtained.", "contents": "Inactivation of glyoxalase I from porcine erythrocytes and yeast by amino-group reagents. Glyoxalase I from porcine erythrocytes and from yeast is inactivated by the amino-group reagents 1-fluoro-2,4-dinitrobenzene, 5-dimethylaminonaphthalene-1-sulfonyl chloride, and 2,4,6-trinitrobenzenesulfonate (N-3ph-S). The inactivation follows pseudo-first-order kinetics, and the apparent first-order rate constant increases with pH, indicating that the basic form of a nucleophilic group is modified. The effect of increasing the inactivator concentration was tested with N-3PH-S, and it was found that the apparent rate constant increased to a limiting value. Such a result is consistent with a mechanism involving formation of a reversible inactivator x enzyme complex prior to the actual inactivation. Experiments with erythrocyte glyoxalase I and a variety of sulfhydryl-group reagents failed to show a dependence on sulfhydryl groups for catalytic activity, in contrast to previous results with the yeast enzyme. These experiments seem to exclude the possibility that essential sulfhydryl groups of the erythrocyte enzyme are modified by the amino-group reagents. Failure of reactivation of yeast glyoxalase I, and the similarities with the erythrocyte enzyme suggest that yeast glyoxalase I is not modified at essential sulfhydryl groups either by the latter reagents. This assumption has further support from experiments involving simultaneous inactivation with amino and sulfhydryl-group reagents. The results are consistent with the interpretation that amino groups of glyoxalase I are essential for catalytic activity. Glutathione derivatives, which are reversible competitive inhibitors of glyoxalase I, were found to protect the enzyme against inactivation by amino-group reagents. However, the concentration required for half-maximal protection was considerably higher than the inhibition constant of the reversible inhibition, which indicates that at least two molecules of the protector must be bound to the enzyme before full protection is obtained."}
{"id": "PMID:237757", "title": "Characterization of an inducible amidase from Pseudomonas acidovorans AE1.", "content": "The main molecular and catalytic properties of an acetanilide-hydrolyzing enzyme from Pseudomonas acidovorans AE 1, purified to a homogeneous state, were investigated. The molecular weight was 57 500 as determined by gel filtration and 55 300 as computed from the amino acid composition. By polyacrylamide gel electrophoresis in dodecylsulfate a polypeptide chain weight of 56 700 was obtained. Based on the reaction of the highly purufied enzyme with diethyl-4-nitrophenyl phosphate an equivalent weight of approximately 59 100 was found. From these results it was concluded that the enzyme consists of a single polypeptide chain and contains one active site per molecule. The enzyme hydrolyzed esters as well as certain aromatic amides. It also catalysed the transfer of acetyl groups to phenetidine yielding phenacetin. The activities towards aliphatic esters were much smaller. The enzyme was stable at pH values ranging from 7 to 9 and its pH-optimum was about 10. It was strongly inhibited by organophosphorous compounds, like diethyl-4-nitrophenyl phosphate or diisopropylphosphorofluoridate, as well as by physostigmine sulfate and -SH-blocking reagents, like HgCl-2 or 4-chloromercuribenzoic acid. o-Nitrophenol caused a competitive inhibition and phenetidine an uncompetitive inhibition.", "contents": "Characterization of an inducible amidase from Pseudomonas acidovorans AE1. The main molecular and catalytic properties of an acetanilide-hydrolyzing enzyme from Pseudomonas acidovorans AE 1, purified to a homogeneous state, were investigated. The molecular weight was 57 500 as determined by gel filtration and 55 300 as computed from the amino acid composition. By polyacrylamide gel electrophoresis in dodecylsulfate a polypeptide chain weight of 56 700 was obtained. Based on the reaction of the highly purufied enzyme with diethyl-4-nitrophenyl phosphate an equivalent weight of approximately 59 100 was found. From these results it was concluded that the enzyme consists of a single polypeptide chain and contains one active site per molecule. The enzyme hydrolyzed esters as well as certain aromatic amides. It also catalysed the transfer of acetyl groups to phenetidine yielding phenacetin. The activities towards aliphatic esters were much smaller. The enzyme was stable at pH values ranging from 7 to 9 and its pH-optimum was about 10. It was strongly inhibited by organophosphorous compounds, like diethyl-4-nitrophenyl phosphate or diisopropylphosphorofluoridate, as well as by physostigmine sulfate and -SH-blocking reagents, like HgCl-2 or 4-chloromercuribenzoic acid. o-Nitrophenol caused a competitive inhibition and phenetidine an uncompetitive inhibition."}
{"id": "PMID:237758", "title": "Proton-magnetic-resonance spectroscopic study of the histidine residues of bovine alpha-lactalbumin.", "content": "A study of the three histidine residues of bovine alpha-lactalbumin has been made using proton magnetic resonance (PMR) spectroscopy in order to obtain information on their environments in the protein and thereby to test in part the previously proposed structure. PMR titration curves are obtained for the H-4 resonances using difference spectroscopy and for the H-2 resonances and the 1-H-2-H exchange rates of the H-2 protons have been measured. The assignment of resonances to particular histidine residues is achieved by utilising their selective reaction with iodoacetate in conjunction with a PMR study of the carboxymethylation of alpha-N-acetyl-L-histidine. The H-2 and H-4 resonances labelled 1, 2 and 3 starting from the downfield end of the spectrum are assigned to histidine residues 107, 68 and 32 respectively. Their apparent pK values at low ionic strength and 20 degrees C are 5.78, 6.49 and 6.51 respectively. The experimental results on two histidine residues are consistent with the predictions of the proposed structure, which indicate that histidine-68 is an external residue and histidine-32 is partially buried and in the vicinity of aromatic residues. The experimental data on histidine 107 can also be rationalised with less certainty in terms of the proposed structure, which indicates a partially buried residue that may be involved in hydrogen bonding.", "contents": "Proton-magnetic-resonance spectroscopic study of the histidine residues of bovine alpha-lactalbumin. A study of the three histidine residues of bovine alpha-lactalbumin has been made using proton magnetic resonance (PMR) spectroscopy in order to obtain information on their environments in the protein and thereby to test in part the previously proposed structure. PMR titration curves are obtained for the H-4 resonances using difference spectroscopy and for the H-2 resonances and the 1-H-2-H exchange rates of the H-2 protons have been measured. The assignment of resonances to particular histidine residues is achieved by utilising their selective reaction with iodoacetate in conjunction with a PMR study of the carboxymethylation of alpha-N-acetyl-L-histidine. The H-2 and H-4 resonances labelled 1, 2 and 3 starting from the downfield end of the spectrum are assigned to histidine residues 107, 68 and 32 respectively. Their apparent pK values at low ionic strength and 20 degrees C are 5.78, 6.49 and 6.51 respectively. The experimental results on two histidine residues are consistent with the predictions of the proposed structure, which indicate that histidine-68 is an external residue and histidine-32 is partially buried and in the vicinity of aromatic residues. The experimental data on histidine 107 can also be rationalised with less certainty in terms of the proposed structure, which indicates a partially buried residue that may be involved in hydrogen bonding."}
{"id": "PMID:237759", "title": "On the mechanism of malonyl-CoA-independent fatty-acid synthesis. Characterization of the mitochondrial chain-elongating system of rat liver and pig-kidney cortex.", "content": "1. Chain elongation of fatty acids by extracts of mitochondrial acetone powders from rat liver and pig kidney cortex are similar in their properties. The specific activity of the kidney system is about 30% as compared to the liver system 2. Different incorporation rates [1-14-C] acetate into fatty acids in the presence of NADH as the sole hydrogen donor that were reported in literature can be explained by different extraction methods. 3. In liver the incorporation into the saturated fatty acid, elongated by one C-2 unit, amounts to only 19% with NADH and 60% with NADPH in comparison with the incorporation in presence of both nucleotides. 4. Kinetics of the chain-elongating process favour the enoyl-CoA reductase to be the rate limiting step. 5. Long-chain saturated and unsaturated fatty acyl-CoA derivatives are very poor primers of the chain elongation. 6. Possion and the enoyl-CoA reductase may be the transfer of hydrogen from NADPH to the respiratory chain, and the conservation of reducing equivalents (NADH and NADPH) or acetate units during cellular anoxia.", "contents": "On the mechanism of malonyl-CoA-independent fatty-acid synthesis. Characterization of the mitochondrial chain-elongating system of rat liver and pig-kidney cortex. 1. Chain elongation of fatty acids by extracts of mitochondrial acetone powders from rat liver and pig kidney cortex are similar in their properties. The specific activity of the kidney system is about 30% as compared to the liver system 2. Different incorporation rates [1-14-C] acetate into fatty acids in the presence of NADH as the sole hydrogen donor that were reported in literature can be explained by different extraction methods. 3. In liver the incorporation into the saturated fatty acid, elongated by one C-2 unit, amounts to only 19% with NADH and 60% with NADPH in comparison with the incorporation in presence of both nucleotides. 4. Kinetics of the chain-elongating process favour the enoyl-CoA reductase to be the rate limiting step. 5. Long-chain saturated and unsaturated fatty acyl-CoA derivatives are very poor primers of the chain elongation. 6. Possion and the enoyl-CoA reductase may be the transfer of hydrogen from NADPH to the respiratory chain, and the conservation of reducing equivalents (NADH and NADPH) or acetate units during cellular anoxia."}
{"id": "PMID:237760", "title": "The conformation of the RNA in cowpea chlorotic mottle virus: dye-binding studies.", "content": "The binding of the dye acridine orange to cowpea chlorotic mottle virus (CCMV) and its purified RNA has been studied to obtain the number of dye-binding sites as a function of pH and, through further analysis, to estimate the degree of RNA secondary structure in situ. Acridine organe does not bind to CCMV protein and so the dye binding directly reflects the accessibility and structure of the RNA. The number of dye molecules per nucleotide which can be bound by native virus (pH 4.5, I = 0.1 buffer) is 0.13-0.18, the precise value depending upon the assumption of either heterogeneous binding sites or weak binding forces. The number of binding sites increases by a factor of about 2.7 to 0.34-0.48 when the pH is raised to pH 7.5 and \"swelling\" of the virus occurs. About 50% of the sites on the free RNA are available to bind dye in the swollen virus. The stacking coefficient, which is a measure of the degree of base pairing in a polynucleotide, has been calculated for the native  and swollen virus and for the isolated RNA. The values of the stacking coefficient for the RNA in the virus and following extraction are comparable, which suggests that the structure of the RNA in both cases is similar, and the values are low in magnitude, which indicates the existence of extensive regions of double-helix.", "contents": "The conformation of the RNA in cowpea chlorotic mottle virus: dye-binding studies. The binding of the dye acridine orange to cowpea chlorotic mottle virus (CCMV) and its purified RNA has been studied to obtain the number of dye-binding sites as a function of pH and, through further analysis, to estimate the degree of RNA secondary structure in situ. Acridine organe does not bind to CCMV protein and so the dye binding directly reflects the accessibility and structure of the RNA. The number of dye molecules per nucleotide which can be bound by native virus (pH 4.5, I = 0.1 buffer) is 0.13-0.18, the precise value depending upon the assumption of either heterogeneous binding sites or weak binding forces. The number of binding sites increases by a factor of about 2.7 to 0.34-0.48 when the pH is raised to pH 7.5 and \"swelling\" of the virus occurs. About 50% of the sites on the free RNA are available to bind dye in the swollen virus. The stacking coefficient, which is a measure of the degree of base pairing in a polynucleotide, has been calculated for the native  and swollen virus and for the isolated RNA. The values of the stacking coefficient for the RNA in the virus and following extraction are comparable, which suggests that the structure of the RNA in both cases is similar, and the values are low in magnitude, which indicates the existence of extensive regions of double-helix."}
{"id": "PMID:237761", "title": "Content, synthesis and degradation of acetyl-coenzyme A carboxylase in the liver of growing chicks.", "content": "Immunochemical techniques were used to study the mechanism underlying the marked increase in the level of acetyl-coenzyme A carboxylase activity in chick liver observed after hatching. The results of immunochemical titrations and Ouchterlony double-diffusion analysis indicated that this increase in the activity level of the enzyme was due to an elevation in the enzyme quantity. Isotopic leucine incorporation studies revealed that the rate of synthesis of the enzyme per liver was 18-fold higher in 9-day-old chicks than in 1-day-old chicks. In terms of the synthesis rate per gram of liver, this increase was 5-fold. The half-life for degradation of the enzyme in 9-day-old chicks was shown to be 46 h, whereas no apparent degradation of the enzyme as well as of total soluble liver protein was observed in 1-day-old chicks. These results indicate that the increase in the hepatic acetyl-CoA carboxylase content in growing chicks can be ascribed to accelerated synthesis of the enzyme.", "contents": "Content, synthesis and degradation of acetyl-coenzyme A carboxylase in the liver of growing chicks. Immunochemical techniques were used to study the mechanism underlying the marked increase in the level of acetyl-coenzyme A carboxylase activity in chick liver observed after hatching. The results of immunochemical titrations and Ouchterlony double-diffusion analysis indicated that this increase in the activity level of the enzyme was due to an elevation in the enzyme quantity. Isotopic leucine incorporation studies revealed that the rate of synthesis of the enzyme per liver was 18-fold higher in 9-day-old chicks than in 1-day-old chicks. In terms of the synthesis rate per gram of liver, this increase was 5-fold. The half-life for degradation of the enzyme in 9-day-old chicks was shown to be 46 h, whereas no apparent degradation of the enzyme as well as of total soluble liver protein was observed in 1-day-old chicks. These results indicate that the increase in the hepatic acetyl-CoA carboxylase content in growing chicks can be ascribed to accelerated synthesis of the enzyme."}
{"id": "PMID:237762", "title": "Modulation of the activity of insulin-dependent enzymes of lipogenesis by glucocorticoids.", "content": "Administration of triamcinolone or dexamethasone to rats led to a prompt, marked and persistent rise in liver acetyl-CoA carboxylase activity. The activity of fatty acid synthetase increased to a lesser extent and after a more prolonged glucocorticoid treatment, whereas the changes in that of NADP-malate dehydrogenase and ATP-citrate lyase were not appreciable. The overall channeling of [1-14-C]acetyl-CoA to fatty acids was enhanced. The triamcinolone effect on acetyl-CoA carboxylase activity appeared to be dependent on the coincident hyperinsulinemia since it was not obtained in alloxan-diabetic rats, whereas the alanine-aminotransferase-inducing effect of this hormone was additive to that of insulin deficiency. In adipose tissue triamcinolone treatment caused a reduction in the activity of all lipogenesis enzymes and blunted their response to insulin administration. The antagonism of glucocorticoids toward insulin, selectively modulating the responses of the insulin-sensitive enzymes in liver and adipose tissue is discussed. The rise in hepatic lipogenic capacity, through the retention of the ability of insulin to induce acetyl-CoA carboxylase, may be physiologically important in restraining the ketogenesis from acetyl-CoA despite the increased fat utilization during glucocorticoid excess.", "contents": "Modulation of the activity of insulin-dependent enzymes of lipogenesis by glucocorticoids. Administration of triamcinolone or dexamethasone to rats led to a prompt, marked and persistent rise in liver acetyl-CoA carboxylase activity. The activity of fatty acid synthetase increased to a lesser extent and after a more prolonged glucocorticoid treatment, whereas the changes in that of NADP-malate dehydrogenase and ATP-citrate lyase were not appreciable. The overall channeling of [1-14-C]acetyl-CoA to fatty acids was enhanced. The triamcinolone effect on acetyl-CoA carboxylase activity appeared to be dependent on the coincident hyperinsulinemia since it was not obtained in alloxan-diabetic rats, whereas the alanine-aminotransferase-inducing effect of this hormone was additive to that of insulin deficiency. In adipose tissue triamcinolone treatment caused a reduction in the activity of all lipogenesis enzymes and blunted their response to insulin administration. The antagonism of glucocorticoids toward insulin, selectively modulating the responses of the insulin-sensitive enzymes in liver and adipose tissue is discussed. The rise in hepatic lipogenic capacity, through the retention of the ability of insulin to induce acetyl-CoA carboxylase, may be physiologically important in restraining the ketogenesis from acetyl-CoA despite the increased fat utilization during glucocorticoid excess."}
{"id": "PMID:237763", "title": "Intermediates of the gamma-glutamyl cycle in mouse tissues. Influence of administration of amino acids on pyrrolidone carboxylate and gamma-glutamyl amino acids.", "content": "GAMMA-Glutamyl transpeptidase, gamma-glutamyl cyclotransferase, L-pyrrolidone carboxylate hydrolase, gamma-glutamylcysteine synthetase and glutathione synthetase, the enzymes of the gamma-glutamyl cycle, were found in mouse brain, liver and kidney. The activity of L-pyrrolidone carboxylate hydrolase was many times lower than the activities of the other enzymes, and thus the conversion of L-pyrrolidone carboxylate to L-glutamate is likely to be the rate-limiting step of the cycle. The specificity of gamma-glutamyl cyclotransferase from mouse tissues was similar to that from rat tissues. The concentration of pyrrolidone carboxylate and gamma-glutamyl amino acids, intermediates of the gamma-glutamyl cycle, was determined by a gas chromatographic procedure coupled with electron capture detection. Administration of L-2-aminobutyrate, an amino acid that is utilized as substrate in the reaction catalyzed by gamma-glutamylcysteine synthetase, led to a large accumulation of gamma-glutamyl-2-aminobutyrate and pyrrolidone carboxylate in mouse tissues. L-Methionine-RS-sulfoximine, an inhibitor of gamma-glutamylcysteine synthetase, abolished the increase in concentration of pyrrolidone carboxylate. No accumulation of pyrrolidone carboxylate was observed after L-cysteine. The separate administration of several protein amino acids had little effect on the concentration of pyrrolidone carboxylate; however formation of small amounts of the corresponding gamma-glutamyl derivatives (e.g. gamma-glutamylmethionine and gamma-glutamylphenylalanine) was detected. These intermediates are probably formed by transpeptidation between glutathione and the corresponding amino acid, catalyzed by gamma-glutamyl transpeptidase. The concentration of pyrrolidone carboxylate increased significantly after administration of a mixture containing all protein amino acids, the highest increase occurring in the kidney. The results suggest that two separate pathways for the formation of gamma-glutamyl amino acids and pyrrolidone carboxylate exist in vivo. One of these results from the function of gamma-glutamylcysteine synthetase in glutathione synthesis. The other pathway involves the amino-acid-dependent degradation of glutathione, mediatedby gamma-glutamyl transpeptidase. Only very small amounts of free intermediates are apparently derived from the latter pathway, suggesting that the gamma-glutamyl amino acids formed in this pathway are either enzyme-bound or are directly hydrolyzed to glutamate and free amino acid.", "contents": "Intermediates of the gamma-glutamyl cycle in mouse tissues. Influence of administration of amino acids on pyrrolidone carboxylate and gamma-glutamyl amino acids. GAMMA-Glutamyl transpeptidase, gamma-glutamyl cyclotransferase, L-pyrrolidone carboxylate hydrolase, gamma-glutamylcysteine synthetase and glutathione synthetase, the enzymes of the gamma-glutamyl cycle, were found in mouse brain, liver and kidney. The activity of L-pyrrolidone carboxylate hydrolase was many times lower than the activities of the other enzymes, and thus the conversion of L-pyrrolidone carboxylate to L-glutamate is likely to be the rate-limiting step of the cycle. The specificity of gamma-glutamyl cyclotransferase from mouse tissues was similar to that from rat tissues. The concentration of pyrrolidone carboxylate and gamma-glutamyl amino acids, intermediates of the gamma-glutamyl cycle, was determined by a gas chromatographic procedure coupled with electron capture detection. Administration of L-2-aminobutyrate, an amino acid that is utilized as substrate in the reaction catalyzed by gamma-glutamylcysteine synthetase, led to a large accumulation of gamma-glutamyl-2-aminobutyrate and pyrrolidone carboxylate in mouse tissues. L-Methionine-RS-sulfoximine, an inhibitor of gamma-glutamylcysteine synthetase, abolished the increase in concentration of pyrrolidone carboxylate. No accumulation of pyrrolidone carboxylate was observed after L-cysteine. The separate administration of several protein amino acids had little effect on the concentration of pyrrolidone carboxylate; however formation of small amounts of the corresponding gamma-glutamyl derivatives (e.g. gamma-glutamylmethionine and gamma-glutamylphenylalanine) was detected. These intermediates are probably formed by transpeptidation between glutathione and the corresponding amino acid, catalyzed by gamma-glutamyl transpeptidase. The concentration of pyrrolidone carboxylate increased significantly after administration of a mixture containing all protein amino acids, the highest increase occurring in the kidney. The results suggest that two separate pathways for the formation of gamma-glutamyl amino acids and pyrrolidone carboxylate exist in vivo. One of these results from the function of gamma-glutamylcysteine synthetase in glutathione synthesis. The other pathway involves the amino-acid-dependent degradation of glutathione, mediatedby gamma-glutamyl transpeptidase. Only very small amounts of free intermediates are apparently derived from the latter pathway, suggesting that the gamma-glutamyl amino acids formed in this pathway are either enzyme-bound or are directly hydrolyzed to glutamate and free amino acid."}
{"id": "PMID:237767", "title": "The ability of cell fractions of mouse spleen to repopulate the hemopoietic tissue and to mount graft-versus-host reaction.", "content": "Mouse spleen cells were separated into seven fractions on a discontinuous gradient of dextran. The lightest, uppermost fraction contained colony-forming units and was capable of repopulating the hemopoietic tissues damaged by irradiation. The fraction below it also contained the colony-forming units, but its repopulating ability was limited. Heavy fractions contained immunocompetent cells capable of mounting graft-versus-host reaction, but the performance of the cells depended on the type of assay, i.e. on whether the cells were assayed in irradiated or in non-irradiated recipients. It is concluded, firstly, that the technique used resolved the colony-forming units into two classes - those capable of self-renewal and those committed to differentiation - which were concentrated in different portions of the light part of the gradient; and secondly, that the cells implementing graft-versus-host reaction were probably also resolved into two classes - the inciting and the proliferating cells - which were concentrated in different portions of the heavy part of the gradient.", "contents": "The ability of cell fractions of mouse spleen to repopulate the hemopoietic tissue and to mount graft-versus-host reaction. Mouse spleen cells were separated into seven fractions on a discontinuous gradient of dextran. The lightest, uppermost fraction contained colony-forming units and was capable of repopulating the hemopoietic tissues damaged by irradiation. The fraction below it also contained the colony-forming units, but its repopulating ability was limited. Heavy fractions contained immunocompetent cells capable of mounting graft-versus-host reaction, but the performance of the cells depended on the type of assay, i.e. on whether the cells were assayed in irradiated or in non-irradiated recipients. It is concluded, firstly, that the technique used resolved the colony-forming units into two classes - those capable of self-renewal and those committed to differentiation - which were concentrated in different portions of the light part of the gradient; and secondly, that the cells implementing graft-versus-host reaction were probably also resolved into two classes - the inciting and the proliferating cells - which were concentrated in different portions of the heavy part of the gradient."}
{"id": "PMID:237782", "title": "Modification by calcium dobesilate of histamine effects on capillary ultrastructure.", "content": "The ultrastructure of blood capillaries and venules are studied in rat skin. After i.v. injection of histamine the luminal surface of the endothelial cells show protrusions of variable size. Numerous gaps have been found in the capillary wall, specially in the venules. These alterations are not observed in the animals that were treated with calcium dobesilate before the administration of histamine. In these cases the capillary structure are indistinguishable of the controls. The possible effects of the histamine and calcium dobesilate on the cell coat and cell junctions of the endothelial capillary cells are discussed.", "contents": "Modification by calcium dobesilate of histamine effects on capillary ultrastructure. The ultrastructure of blood capillaries and venules are studied in rat skin. After i.v. injection of histamine the luminal surface of the endothelial cells show protrusions of variable size. Numerous gaps have been found in the capillary wall, specially in the venules. These alterations are not observed in the animals that were treated with calcium dobesilate before the administration of histamine. In these cases the capillary structure are indistinguishable of the controls. The possible effects of the histamine and calcium dobesilate on the cell coat and cell junctions of the endothelial capillary cells are discussed."}
{"id": "PMID:237799", "title": "Hyperosmolar nature of diabetic coma.", "content": "Stupor in patients with nonketotic hyperglycemia has been ascribed to hyperosmolarity, but the cause of depressed consciousness in patients with ketoacidosis has been puzzling. In this study, blood pH, serum glucose and sodium concentrations, and serum osmolality were measured in eighty-five consecutive episodes of diabetic ketoacidosis and forty-seven of nonketotic hyperglycemia. In the acidotic patients, as in those with nonketotic hyperglycemia, stupor closely paralleled hyperosmolarity and not the severity of acidemia. Indeed, the mean elevations of serum osmolarity were almost the same in the ketotic and in the nonketotic patients who were deeply obtunded. It seems likely that depression of consciousness in patients with severely uncontrolled diabetes mellitus, if not due to a nonmetabolic disorder, such as acute stroke, is attributable to hyperosmolarity, whether or not ketoacidosis is present.", "contents": "Hyperosmolar nature of diabetic coma. Stupor in patients with nonketotic hyperglycemia has been ascribed to hyperosmolarity, but the cause of depressed consciousness in patients with ketoacidosis has been puzzling. In this study, blood pH, serum glucose and sodium concentrations, and serum osmolality were measured in eighty-five consecutive episodes of diabetic ketoacidosis and forty-seven of nonketotic hyperglycemia. In the acidotic patients, as in those with nonketotic hyperglycemia, stupor closely paralleled hyperosmolarity and not the severity of acidemia. Indeed, the mean elevations of serum osmolarity were almost the same in the ketotic and in the nonketotic patients who were deeply obtunded. It seems likely that depression of consciousness in patients with severely uncontrolled diabetes mellitus, if not due to a nonmetabolic disorder, such as acute stroke, is attributable to hyperosmolarity, whether or not ketoacidosis is present."}
{"id": "PMID:237800", "title": "Amelioration of hypoglycemia in a patient with malignant insulinoma during the development of the ectopic ACTH syndrome.", "content": "A patient with functioning islet cell carcinoma is described who had amelioration of her hypoglycemia during the development of ectopic ACTH syndrome. Moon facies and hyperkalemic metabolic acidosis were also present in this patient, features uncommonly seen in the actopic ACTH syndrome. At autopsy, she was found to have active tuberculosis. Prophylactic antituberculous therapy should be given to high-risk patients with the ectopic ACTH syndrome. High doses of ACTH may be palliative in refractory hypoglycemic states.", "contents": "Amelioration of hypoglycemia in a patient with malignant insulinoma during the development of the ectopic ACTH syndrome. A patient with functioning islet cell carcinoma is described who had amelioration of her hypoglycemia during the development of ectopic ACTH syndrome. Moon facies and hyperkalemic metabolic acidosis were also present in this patient, features uncommonly seen in the actopic ACTH syndrome. At autopsy, she was found to have active tuberculosis. Prophylactic antituberculous therapy should be given to high-risk patients with the ectopic ACTH syndrome. High doses of ACTH may be palliative in refractory hypoglycemic states."}
{"id": "PMID:237802", "title": "Rectal potential difference in the diagnosis of aldosterone excess.", "content": "Rectal potential difference (pd) is directly related to the plasma aldosterone concentration, and rises when aldosterone is stimulated by sodium deprivation. However, when the measurement of rectal pd was tested at a screening test for hyperaldosteronism in 19 hypertensive subjects, four of the eight with primary hyperaldosteronism had a normal pd and four of the eight without aldosterone excess had an abnormally raised potential difference. The technique cannot therefore be recommended as a routine screening test for hyperaldosteronism. No relationship was found between rectal pd and hypertension associated with excess of deoxycorticosterone. Rectal pd rises in response to the mineralocorticoid-like agent carbenoxolone.", "contents": "Rectal potential difference in the diagnosis of aldosterone excess. Rectal potential difference (pd) is directly related to the plasma aldosterone concentration, and rises when aldosterone is stimulated by sodium deprivation. However, when the measurement of rectal pd was tested at a screening test for hyperaldosteronism in 19 hypertensive subjects, four of the eight with primary hyperaldosteronism had a normal pd and four of the eight without aldosterone excess had an abnormally raised potential difference. The technique cannot therefore be recommended as a routine screening test for hyperaldosteronism. No relationship was found between rectal pd and hypertension associated with excess of deoxycorticosterone. Rectal pd rises in response to the mineralocorticoid-like agent carbenoxolone."}
{"id": "PMID:237803", "title": "The effects of premedication drugs on the lower oesophageal high pressure zone and reflux status of rhesus monkeys and man.", "content": "Thirty-five human  volunteers and eight Rhesus monkeys were studied with standard gastrooesophageal manometric techniqes and their  reflux status was evaluated witha pH probe placed in the lower oesophagus. morphine sulphate, pethidine hydrochloride, or idazepam was given intravenously until drowsiness was induced. The manometric and pH studies were repeated. All three drugs decreased the lower oesophageal high pressure zone and increased the probability of relux in both monkeys and man. Thes findings are relevant in the preparation of patients for surgery since gastrooesophageal reflux and pulmonary aspiration may be a problen in the pre-and postoperative phases.", "contents": "The effects of premedication drugs on the lower oesophageal high pressure zone and reflux status of rhesus monkeys and man. Thirty-five human  volunteers and eight Rhesus monkeys were studied with standard gastrooesophageal manometric techniqes and their  reflux status was evaluated witha pH probe placed in the lower oesophagus. morphine sulphate, pethidine hydrochloride, or idazepam was given intravenously until drowsiness was induced. The manometric and pH studies were repeated. All three drugs decreased the lower oesophageal high pressure zone and increased the probability of relux in both monkeys and man. Thes findings are relevant in the preparation of patients for surgery since gastrooesophageal reflux and pulmonary aspiration may be a problen in the pre-and postoperative phases."}
{"id": "PMID:237807", "title": "Temporary, reversible binding of the competence factor to cellular receptors of Pneumococcus during induction of competence.", "content": "The binding of the competence factor to cellular receptors of physiologically non-competent cells of Pneumococcus was followed as a function of time. A transformation medium without bovine serum albumin was used to study the binding of the competence factor. Control cells without the added factor remained completely non-competent under these conditions. The maximal binding of the factor to the cellular receptors took place already after 3 min of contact of the cells with the factor at 37 degrees C. After 10 min, when the maximum induction of competence occurs in the system used, the competence factor is fully released from the receptors to the medium. It follows that within the period between the 3rd and 10th min, when the cells are being modified for the irreversible binding of DNA, the presence of the competence factor on the cells is no longer necessary.", "contents": "Temporary, reversible binding of the competence factor to cellular receptors of Pneumococcus during induction of competence. The binding of the competence factor to cellular receptors of physiologically non-competent cells of Pneumococcus was followed as a function of time. A transformation medium without bovine serum albumin was used to study the binding of the competence factor. Control cells without the added factor remained completely non-competent under these conditions. The maximal binding of the factor to the cellular receptors took place already after 3 min of contact of the cells with the factor at 37 degrees C. After 10 min, when the maximum induction of competence occurs in the system used, the competence factor is fully released from the receptors to the medium. It follows that within the period between the 3rd and 10th min, when the cells are being modified for the irreversible binding of DNA, the presence of the competence factor on the cells is no longer necessary."}
{"id": "PMID:237834", "title": "Biochemical and immunological properties of ribonucleic acid-rich extracts from Francisella tularensis.", "content": "Ribonucleic acid (RNA)-rich extracts derived from the attenuated strain of Francisella tularensis (strain LVS) protected Swiss mice against lethal challenge with F. tularensis strain 425 but not against strain SCHU S4. No killed preparation, including an RNA-rich extract from SCHU S4 itself, offered protection against strain SCHU S4 in contrast to the high level of protection offered against this strain by vaccination with live strain LVS. The protective activity observed against strain 425 was sensitive to ribonuclease but not to Pronase. Protective activity is not a general property of bacterial RNA, since RNA-rich extracts from Staphylococcus aureus offered no protection against tularemia, although disc gel electrophoresis showed similar kinds and amounts of RNA in preparations form F. tularensis and S. aureus. Furthermore, inability to localize activity to a specific region in sucrose gradients suggests a structural rather than an informational role for the RNA in such extracts. RNA-rich extracts from F. tularensis but not from S. aureus were efficient inducers of F. tularensis opsonins in mouse serum, suggesting one mechanism by which such extracts confer protection.", "contents": "Biochemical and immunological properties of ribonucleic acid-rich extracts from Francisella tularensis. Ribonucleic acid (RNA)-rich extracts derived from the attenuated strain of Francisella tularensis (strain LVS) protected Swiss mice against lethal challenge with F. tularensis strain 425 but not against strain SCHU S4. No killed preparation, including an RNA-rich extract from SCHU S4 itself, offered protection against strain SCHU S4 in contrast to the high level of protection offered against this strain by vaccination with live strain LVS. The protective activity observed against strain 425 was sensitive to ribonuclease but not to Pronase. Protective activity is not a general property of bacterial RNA, since RNA-rich extracts from Staphylococcus aureus offered no protection against tularemia, although disc gel electrophoresis showed similar kinds and amounts of RNA in preparations form F. tularensis and S. aureus. Furthermore, inability to localize activity to a specific region in sucrose gradients suggests a structural rather than an informational role for the RNA in such extracts. RNA-rich extracts from F. tularensis but not from S. aureus were efficient inducers of F. tularensis opsonins in mouse serum, suggesting one mechanism by which such extracts confer protection."}
{"id": "PMID:237835", "title": "Relationship of serum beta-glucuronidase and lysozyme to pathogenesis of tularemia in immune and nonimmune rats.", "content": "A temporal study is reported of the febrile responses, tissue bacterial contents, and serum concentration of the lysosomal enzymes, beta-glucuronidase and lysozyme, in nonimmune rats inoculated with virulent or attenuated strains of Francisella tularensis, and in immune rats challenged with either a high or low dose of virulent organisms. The level of serum beta-glucuronidase appears to be an indicator of hepatocyte damage, whereas serum lysozyme correlates with the appearance, frequency, and severity of pyogranulomatous lesions. Survival of nonimmune rats after a challenge with either virulent or attenuated organisms appears to depend on a balance between dose of bacterial inoculum, celerity of irreversible pathologic events, and the ability of the reticuloendothelial and immune systems to collaboratively mount a response to limit or prevent dissemination of the infection. In immune rats, infection of parenchymal hepatic cells does not occur after a low dose (10-4) virulent challenge. Infection of parenchymal hepatic cells, however, does occur in immunized rats when the challenge dose is sufficiently large (10-8) so as to overcome the capacity of the reticuloendothelial to clear opsonized organisms.", "contents": "Relationship of serum beta-glucuronidase and lysozyme to pathogenesis of tularemia in immune and nonimmune rats. A temporal study is reported of the febrile responses, tissue bacterial contents, and serum concentration of the lysosomal enzymes, beta-glucuronidase and lysozyme, in nonimmune rats inoculated with virulent or attenuated strains of Francisella tularensis, and in immune rats challenged with either a high or low dose of virulent organisms. The level of serum beta-glucuronidase appears to be an indicator of hepatocyte damage, whereas serum lysozyme correlates with the appearance, frequency, and severity of pyogranulomatous lesions. Survival of nonimmune rats after a challenge with either virulent or attenuated organisms appears to depend on a balance between dose of bacterial inoculum, celerity of irreversible pathologic events, and the ability of the reticuloendothelial and immune systems to collaboratively mount a response to limit or prevent dissemination of the infection. In immune rats, infection of parenchymal hepatic cells does not occur after a low dose (10-4) virulent challenge. Infection of parenchymal hepatic cells, however, does occur in immunized rats when the challenge dose is sufficiently large (10-8) so as to overcome the capacity of the reticuloendothelial to clear opsonized organisms."}
{"id": "PMID:237836", "title": "Nature of the Kanagawa phenomenon of Vibrio parahaemolyticus.", "content": "In a study of the Kanagawa phenomenon of Vibrio parahaemolyticus, both Kanagawa-positive and -negative strains were found to produce hemolytic factors that could not be differentiated on Wagatsuma blood agar. The presence of fermentable carbohydrates in media containing high concentrations of NaCl promoted the growth of V. parahaemolyticus and resulted in a marked decrease in medium pH and increased hemolysin production. The Kanagawa hemolysis of test strains differed according to the carbohydrates added. Clearly defined Kanagawa hemolysis was observed in blood agars of high salt content, but the distinction was lost in media containing 3% NaCl. From the results of this study, the Kanagawa hemolysis was interpreted as an expression of quantitative difference in hemolysin production, a conclusion that is clearly demonstrated on special blood agar of high salt content.", "contents": "Nature of the Kanagawa phenomenon of Vibrio parahaemolyticus. In a study of the Kanagawa phenomenon of Vibrio parahaemolyticus, both Kanagawa-positive and -negative strains were found to produce hemolytic factors that could not be differentiated on Wagatsuma blood agar. The presence of fermentable carbohydrates in media containing high concentrations of NaCl promoted the growth of V. parahaemolyticus and resulted in a marked decrease in medium pH and increased hemolysin production. The Kanagawa hemolysis of test strains differed according to the carbohydrates added. Clearly defined Kanagawa hemolysis was observed in blood agars of high salt content, but the distinction was lost in media containing 3% NaCl. From the results of this study, the Kanagawa hemolysis was interpreted as an expression of quantitative difference in hemolysin production, a conclusion that is clearly demonstrated on special blood agar of high salt content."}
{"id": "PMID:237837", "title": "Intrinsic and chemically produced microheterogeneity of Staphylococcus aureus enterotoxin type C.", "content": "Staphylococcus aureus enterotoxins C1 (SEC1) and C2 (SEC2) produced from 50-liter quantities of crude culture supernatants were purified chromatographically in a neutral or acid milieu. Microheterogenity of SEC1 was markedly increased by treatment of the purified toxin with alkali, and new more acidic charged species appeared. SEC2 was more heterogenous than any of the other S. aureus enterotoxins and was affected only slightly by treatment with alkali. Prolonged incubation of the organism during production of the SEC2 produced changes in charged species that may be related to a bacterial deamidase, since similar changes were not seen with alkaline treatment of the purified toxin. Although SEC1 and SEC2 showed complete identity immunologically, they are separate, distinct toxins, and alkali treatment of SEC1 did not produce SEC2.", "contents": "Intrinsic and chemically produced microheterogeneity of Staphylococcus aureus enterotoxin type C. Staphylococcus aureus enterotoxins C1 (SEC1) and C2 (SEC2) produced from 50-liter quantities of crude culture supernatants were purified chromatographically in a neutral or acid milieu. Microheterogenity of SEC1 was markedly increased by treatment of the purified toxin with alkali, and new more acidic charged species appeared. SEC2 was more heterogenous than any of the other S. aureus enterotoxins and was affected only slightly by treatment with alkali. Prolonged incubation of the organism during production of the SEC2 produced changes in charged species that may be related to a bacterial deamidase, since similar changes were not seen with alkaline treatment of the purified toxin. Although SEC1 and SEC2 showed complete identity immunologically, they are separate, distinct toxins, and alkali treatment of SEC1 did not produce SEC2."}
{"id": "PMID:237838", "title": "Epstein-barr virus-induced cap formation in human lymphoblastoid cells.", "content": "Redistribution and consequent cap formation of Epstein-Barr virus adsorbed to human lymphoblastoid cells were studied by indirect membrane immunofluorescence carried out at 0 degrees C. When EBV was adsorbed on cells at 0 degrees C, the cell surface fluorescence had a mostly r-ng-like pattern. However, the ring cells could be transformed into cap cells when warmed at 37 degrees C. This cap formation could be induced by EBV alone without participation of antibodies involved in the immunofluorescence procedure. The cap formation was temperature- and pH-dependent, and was reversibly inhibited by sodium azide or some sugars. Thus the EBV-induced cap formation was analogous to that induced by antibodies or ligands on other lymphoid cells.", "contents": "Epstein-barr virus-induced cap formation in human lymphoblastoid cells. Redistribution and consequent cap formation of Epstein-Barr virus adsorbed to human lymphoblastoid cells were studied by indirect membrane immunofluorescence carried out at 0 degrees C. When EBV was adsorbed on cells at 0 degrees C, the cell surface fluorescence had a mostly r-ng-like pattern. However, the ring cells could be transformed into cap cells when warmed at 37 degrees C. This cap formation could be induced by EBV alone without participation of antibodies involved in the immunofluorescence procedure. The cap formation was temperature- and pH-dependent, and was reversibly inhibited by sodium azide or some sugars. Thus the EBV-induced cap formation was analogous to that induced by antibodies or ligands on other lymphoid cells."}
{"id": "PMID:237839", "title": "Aminoglycosides from the clinical microbiologist's viewpoint.", "content": "The author is discussing the aminoglycosides from the clinical microbiologists viewpoint. It is both an review of the literature and a personal attempt to put into perspective some of his own experience with these agents and reports in the literature. He is discussing the influence of the culture media composition of the outcome of susceptibility tests with these agents as well as the problems of bacterial resistance. Furthermore the topic of rapid and reasonably accurate serum drug level determination. Finally he gives some brief comments to the question of synergism or antagonism with other mainly penicillin type antibiotics.", "contents": "Aminoglycosides from the clinical microbiologist's viewpoint. The author is discussing the aminoglycosides from the clinical microbiologists viewpoint. It is both an review of the literature and a personal attempt to put into perspective some of his own experience with these agents and reports in the literature. He is discussing the influence of the culture media composition of the outcome of susceptibility tests with these agents as well as the problems of bacterial resistance. Furthermore the topic of rapid and reasonably accurate serum drug level determination. Finally he gives some brief comments to the question of synergism or antagonism with other mainly penicillin type antibiotics."}
{"id": "PMID:237841", "title": "Bovine serum albumin in lithium chloride solutions.", "content": "The effects of li+ and H3O+ on the conformation of bovine serum albumin in azqueous solutions at room temperature are compared. At low pH (high concentration of H3O+) the change in conformation of the protein is demonstrated by an increase in effective volume, a decrease in helical content and a blue shift of tyrosyl residue. A similar change is observed for the protein in highly concentrated LiC1 solution (6.0-7.0M) at neutral pH. However, the H3O+ is 12,000 times more powerful than the Li+ in destabilizing the protein molecule. This is consistent with their thermodynamic and kinetic properties, since the H3O+ is often different from the Li+ in several orders of magnitude. While the changes in structural properties of the protein are almost identical in both the acidic solution and the highly concentrated LiC1 solution, further study using dioxane as a probe suggests different mechanisms under which the changes occur. The effect of H3O+ is related to electrostatic force, whereas the effect of Li+ is related to both the electrostatic hydrophobic forces. These two major forces are believed to be responsible for the conformation of protein molecules.", "contents": "Bovine serum albumin in lithium chloride solutions. The effects of li+ and H3O+ on the conformation of bovine serum albumin in azqueous solutions at room temperature are compared. At low pH (high concentration of H3O+) the change in conformation of the protein is demonstrated by an increase in effective volume, a decrease in helical content and a blue shift of tyrosyl residue. A similar change is observed for the protein in highly concentrated LiC1 solution (6.0-7.0M) at neutral pH. However, the H3O+ is 12,000 times more powerful than the Li+ in destabilizing the protein molecule. This is consistent with their thermodynamic and kinetic properties, since the H3O+ is often different from the Li+ in several orders of magnitude. While the changes in structural properties of the protein are almost identical in both the acidic solution and the highly concentrated LiC1 solution, further study using dioxane as a probe suggests different mechanisms under which the changes occur. The effect of H3O+ is related to electrostatic force, whereas the effect of Li+ is related to both the electrostatic hydrophobic forces. These two major forces are believed to be responsible for the conformation of protein molecules."}
{"id": "PMID:237842", "title": "Digestion of insulin derivatives with subtilisin: a kinetic study.", "content": "Native, denatured, performic acid-oxidized or S-sulfo insulin and S-sulfo or performic acid-oxidized A- and B-chains were digested with subtilisin type Carsberg. The proteolysis was followed by measuring the uptake of alkali through autotitration. The kinetic study shows the existence of 2 first-order reaction classes which differ markedly in rate constant. The number of bonds split with fast and with slow reactions has been calculated. Only one of a total of 12 cleavable bonds in native insulin is opened by fast reaction. In the denatured protein the number of bonds split by the fast reaction increases to 4 and in the oxidized and S-sulfo protein 3 bonds are cleaved, while the slow cleavable bonds number 2 and 7, respectively, The kinetic study of the proteolysis of S-sulfo A-chain and of oxidized or S-sulfo B-chain shows that two bonds are split in A-chain with the fast and slow reactions, while in B-chain only one of the six cleavable bonds is susceptible to fast attack.", "contents": "Digestion of insulin derivatives with subtilisin: a kinetic study. Native, denatured, performic acid-oxidized or S-sulfo insulin and S-sulfo or performic acid-oxidized A- and B-chains were digested with subtilisin type Carsberg. The proteolysis was followed by measuring the uptake of alkali through autotitration. The kinetic study shows the existence of 2 first-order reaction classes which differ markedly in rate constant. The number of bonds split with fast and with slow reactions has been calculated. Only one of a total of 12 cleavable bonds in native insulin is opened by fast reaction. In the denatured protein the number of bonds split by the fast reaction increases to 4 and in the oxidized and S-sulfo protein 3 bonds are cleaved, while the slow cleavable bonds number 2 and 7, respectively, The kinetic study of the proteolysis of S-sulfo A-chain and of oxidized or S-sulfo B-chain shows that two bonds are split in A-chain with the fast and slow reactions, while in B-chain only one of the six cleavable bonds is susceptible to fast attack."}
{"id": "PMID:237843", "title": "Carbamylation of alkaline mesentericopeptidas.", "content": "The effects of carbamylation with potassium cyanate, and methylation with methyl p-nitrobenzene sulphonate on the mesentericopeptidase activity are studies. The treatment with potassium cyanate causes the enzyme to lose its activity towards ester substrates and casein. The specific reagent N-trans-cinnamoylimidazole does not acylate the active site in the  carbamylated enzyme. The pH dependence of the rate of inactivation indicates that an ionizing group of pK = 7.3, probably the protonated imidazole group of the active site histidine, is involved in the reaction. The competitive inhibitor boric acid protects mesentericopeptidase against inactivation with potassium cyanate. These suggest that the active site residues are modified in the unprotected enzyme. Sixty per cent of the enzyme activity toward N-acetyl-L-tyrosine ethyl ester was restored after treatment of the carbamylated mesentericopeptidase with 1 M hydroxylamine hydrochloride. Circular dichroism spectra show that the carbamylation does not change markedly the native protein conformation.", "contents": "Carbamylation of alkaline mesentericopeptidas. The effects of carbamylation with potassium cyanate, and methylation with methyl p-nitrobenzene sulphonate on the mesentericopeptidase activity are studies. The treatment with potassium cyanate causes the enzyme to lose its activity towards ester substrates and casein. The specific reagent N-trans-cinnamoylimidazole does not acylate the active site in the  carbamylated enzyme. The pH dependence of the rate of inactivation indicates that an ionizing group of pK = 7.3, probably the protonated imidazole group of the active site histidine, is involved in the reaction. The competitive inhibitor boric acid protects mesentericopeptidase against inactivation with potassium cyanate. These suggest that the active site residues are modified in the unprotected enzyme. Sixty per cent of the enzyme activity toward N-acetyl-L-tyrosine ethyl ester was restored after treatment of the carbamylated mesentericopeptidase with 1 M hydroxylamine hydrochloride. Circular dichroism spectra show that the carbamylation does not change markedly the native protein conformation."}
{"id": "PMID:237844", "title": "A study of the unfolding of the inhibited subtilisin in guanidine hydrochloride.", "content": "Inhibited subtilisin (Subtilism Carlsberg; Subtilopeptidase A) is unfolded in the presence of 7 M guanidine hydrochloride. The unfolding reaches a maximum in approximately 6 min at 20C at pH 8.0. This is demonstrated by an increase of the mean residue ellipticity at 222 nm from -8.02 x 10-3 to -1.72 x 10-3 deg. cm-2/decimole. The unfolding is partially reversible and this reversibility is favoured by lower concentrations of enzyme. The fact that the refolding process is not complete may be attributed to either the demonstrated self association of the denatured enzyme or to interference of non-covalently bound autolysis peptides.", "contents": "A study of the unfolding of the inhibited subtilisin in guanidine hydrochloride. Inhibited subtilisin (Subtilism Carlsberg; Subtilopeptidase A) is unfolded in the presence of 7 M guanidine hydrochloride. The unfolding reaches a maximum in approximately 6 min at 20C at pH 8.0. This is demonstrated by an increase of the mean residue ellipticity at 222 nm from -8.02 x 10-3 to -1.72 x 10-3 deg. cm-2/decimole. The unfolding is partially reversible and this reversibility is favoured by lower concentrations of enzyme. The fact that the refolding process is not complete may be attributed to either the demonstrated self association of the denatured enzyme or to interference of non-covalently bound autolysis peptides."}
{"id": "PMID:237845", "title": "Flavin nucleotides, glutathione reductase and assessment of riboflavin status.", "content": "The in vitro effects of flavin nucleotides on human erythrocyte glutathione reductase were studied. Flavin mononucleotide was found to be a potent inhibitor of glutathione reductase in haemolysates, having an effect at a concentration of 1 muM. Flavin adenine dinucleotide inhibited at a concentration at least ten fold this, lower levels producing the expected stimulation of enzyme activity. Different assay conditions also altered the activity of the enzyme, although the flavin mononucleotide inhibition remained. The implications of these findings in our understanding of glutatione reductase and in using the enzyme to assess riboflavin status are discussed.", "contents": "Flavin nucleotides, glutathione reductase and assessment of riboflavin status. The in vitro effects of flavin nucleotides on human erythrocyte glutathione reductase were studied. Flavin mononucleotide was found to be a potent inhibitor of glutathione reductase in haemolysates, having an effect at a concentration of 1 muM. Flavin adenine dinucleotide inhibited at a concentration at least ten fold this, lower levels producing the expected stimulation of enzyme activity. Different assay conditions also altered the activity of the enzyme, although the flavin mononucleotide inhibition remained. The implications of these findings in our understanding of glutatione reductase and in using the enzyme to assess riboflavin status are discussed."}
{"id": "PMID:237849", "title": "A comparison between bromazepam (Ro 5-3350, Lexotan) and diazepam (Valium) in anxiety neurosis. A controlled, double-blind clinical trial.", "content": "The new benzodiazepine bromazepam (Ro 5-3350, Lexotan) was compared with diazepam in a double-blind, crossover trial on 30 patients with prolonged anxiety symptoms. Each drug was given for 3 weeks in a dose of 5 mg t.d.s. Bromazepam proved to be statistically significantly superior to diazepam when evaluated through patients' preferences. Fourteen patients preferred bromazepam to diazepam and four the opposite. Three cases were tied. Nine patients had to be withdrawn from the evaluation, which may create bias. A plea is made for further controlled clinical trials on bromazepam, in particular in obsessive and phobic neurosis.", "contents": "A comparison between bromazepam (Ro 5-3350, Lexotan) and diazepam (Valium) in anxiety neurosis. A controlled, double-blind clinical trial. The new benzodiazepine bromazepam (Ro 5-3350, Lexotan) was compared with diazepam in a double-blind, crossover trial on 30 patients with prolonged anxiety symptoms. Each drug was given for 3 weeks in a dose of 5 mg t.d.s. Bromazepam proved to be statistically significantly superior to diazepam when evaluated through patients' preferences. Fourteen patients preferred bromazepam to diazepam and four the opposite. Three cases were tied. Nine patients had to be withdrawn from the evaluation, which may create bias. A plea is made for further controlled clinical trials on bromazepam, in particular in obsessive and phobic neurosis."}
{"id": "PMID:237850", "title": "The stability constants of magnesium oxalate complexes.", "content": "The stability constants of MgC204 and Mg2C204-2nCOmplexes were estimated at 37--38 C by four different techniques; there was good agreement among the results of the different techniques. The stability constant of MgC204 is (4019 plus or minus 76 M-minus 1). The stability constant of Mg2C204-2nWAS FOund to be less than 5 M-minus 1. These stability constant are needed in the evaluation of the stone-forming potential of urine.", "contents": "The stability constants of magnesium oxalate complexes. The stability constants of MgC204 and Mg2C204-2nCOmplexes were estimated at 37--38 C by four different techniques; there was good agreement among the results of the different techniques. The stability constant of MgC204 is (4019 plus or minus 76 M-minus 1). The stability constant of Mg2C204-2nWAS FOund to be less than 5 M-minus 1. These stability constant are needed in the evaluation of the stone-forming potential of urine."}
{"id": "PMID:237854", "title": "The effect of thyrotrophin on oxidative activity in thyroid follicle cells.", "content": "Biochemical evidence, based on supra-physiological concentrations of thyrotrophin (TSH), has indicated that this hormone increases the NADP concentration in thyroid follicle cells. The hormone is believed to act both to enhance the reoxidation of the reduced coenzyme and to generate NADP from NAD. The latter effect, mediated by NAD-+-kinase, could be a major control mechanism in thyroid metabolism. In the present study increased sensitivity has been obtained by the use of maintenance culture and of microdensitometry for measuring enzyme activity in the follicle cells. Using low physiological (0.1 muU/ml), and sub-physiological concentrations of the hormone as are used in the cytochemical bioassay systems, it has been shown that the rate of reoxidation of NADPH is enhanced by TSH. Moreover the NAD-+-kinase activity is also greatly increased, and shows a direct relationship to the concentration of the hormone acting on the segments of the gland in vitro. It is possible that this phenomenon could be used to assay TSH. The results indicate that NAD-+-kinase activity may play a significant part in the control of pentose-shunt oxidation in thyroid follicle cells.", "contents": "The effect of thyrotrophin on oxidative activity in thyroid follicle cells. Biochemical evidence, based on supra-physiological concentrations of thyrotrophin (TSH), has indicated that this hormone increases the NADP concentration in thyroid follicle cells. The hormone is believed to act both to enhance the reoxidation of the reduced coenzyme and to generate NADP from NAD. The latter effect, mediated by NAD-+-kinase, could be a major control mechanism in thyroid metabolism. In the present study increased sensitivity has been obtained by the use of maintenance culture and of microdensitometry for measuring enzyme activity in the follicle cells. Using low physiological (0.1 muU/ml), and sub-physiological concentrations of the hormone as are used in the cytochemical bioassay systems, it has been shown that the rate of reoxidation of NADPH is enhanced by TSH. Moreover the NAD-+-kinase activity is also greatly increased, and shows a direct relationship to the concentration of the hormone acting on the segments of the gland in vitro. It is possible that this phenomenon could be used to assay TSH. The results indicate that NAD-+-kinase activity may play a significant part in the control of pentose-shunt oxidation in thyroid follicle cells."}
{"id": "PMID:237853", "title": "Cytochemical discrimination between catalases and peroxidases using diaminobenzidine.", "content": "The influence on diaminobenzidine staining of four variables: prefixation in aldehyde, temperature and pH of incubation, and H2O2 concentration, was investigated in catalase-, as well as in peroxydase-containing material. Catalase from five different sources and five types of peroxidase were examined. It is concluded: (a) when cells are incubated without prior fixation, in a DAB medium at room temperature and pH 7.3 with 0.003% H2O2, peroxidases produce a visible cytochemical stain, while catalases do not; (b) the cytochemical reaction elicited by catalases is stimulated by prior aldehyde fixation in specified conditions, and incubation at 45 degrees C and pH 9.7 with 0.06% H2O2; (c) under the latter circumstances several peroxidases also stain. Ultrastructural preservation is satisfactory in tissues incubated prior to fixation.", "contents": "Cytochemical discrimination between catalases and peroxidases using diaminobenzidine. The influence on diaminobenzidine staining of four variables: prefixation in aldehyde, temperature and pH of incubation, and H2O2 concentration, was investigated in catalase-, as well as in peroxydase-containing material. Catalase from five different sources and five types of peroxidase were examined. It is concluded: (a) when cells are incubated without prior fixation, in a DAB medium at room temperature and pH 7.3 with 0.003% H2O2, peroxidases produce a visible cytochemical stain, while catalases do not; (b) the cytochemical reaction elicited by catalases is stimulated by prior aldehyde fixation in specified conditions, and incubation at 45 degrees C and pH 9.7 with 0.06% H2O2; (c) under the latter circumstances several peroxidases also stain. Ultrastructural preservation is satisfactory in tissues incubated prior to fixation."}
{"id": "PMID:237856", "title": "Cytoplasmic protein network in HeLa cells.", "content": "Monolayer HeLa culture nuclei isolated in situ with nonionic detergents remained attached to the glass as a \"nuclear monolayer\". Searching for nuclear fixing structures a fine continuous protein network was revealed around the isolated nuclei with fluorescence microscope after acridine orange staining.", "contents": "Cytoplasmic protein network in HeLa cells. Monolayer HeLa culture nuclei isolated in situ with nonionic detergents remained attached to the glass as a \"nuclear monolayer\". Searching for nuclear fixing structures a fine continuous protein network was revealed around the isolated nuclei with fluorescence microscope after acridine orange staining."}
{"id": "PMID:237855", "title": "Enzyme histochemical observations on the segmentation of the proximal tubules in the kidney of the female rat.", "content": "The segmentation of the proximal tubules in the kidney of the female rat was studied by means of enzyme histochemical reactions and the results compared with those observed in male and recently described by Jacobsen and J0rgensen (1973 a). Reactions were performed for the following soluble, coezyme-dependent oxido-reductases: glucose 6-phosphate dehydrogenase, alpha-glycerophosphate dehydrogenase, 3 alpha-hydroxysteroid dehydrogenase, NAD-as well as NADP-dependent isocitrate dehydrogenases, NAD-dependent malate dehydrogenase, NADP-dependent, decarboxylating malate dehydrogenase, uridine diphosphate glucose dehydrogenase. Measures were taken to reduce enzyme diffusion and eliminate interference from tissue tetrazolium reductases. Furthermore, reactions were performed for a number of less soluble or insoluble enzymes: glucose 6-phosphatase, mitochondrial alpha-glycerophosphate dehydrogenase, beta-hydroxybutyrate dehydrogenase, succinate dehydrogenase and tetrazolium reductases. In the proximal tubules of the female rat all enzymes studied--except beta-hydroxybutyrate dehydrogenase--showed segmental differences, most of them clearly revealing three segments. Sex differences were found concerning all enzymes except uridine diphosphate glucose dehydrogenase and NADP-dependent isocitrate dehydrogenase. The most pronounced sex-related differences were seen in the third segment in which part the male rat showed highest activity in respect to tetrazolium reductases, NAD-dependent isocitrate dehydrogenase, succinate dehydrogenase, beta-hydroxybutyrate dehydrogenase, 3 alpha-hydroxysteroid dehydrogenase and glucose 6-phosphate dehydrogenase and the female in respect to glucose 6-phosphatase, alpha-glycerophosphate dehydrogenases, and NADP-dependent, decarboxylating malate dehydrogenase. A few of the enzymes exhibited minor sex differences in the first two segments.", "contents": "Enzyme histochemical observations on the segmentation of the proximal tubules in the kidney of the female rat. The segmentation of the proximal tubules in the kidney of the female rat was studied by means of enzyme histochemical reactions and the results compared with those observed in male and recently described by Jacobsen and J0rgensen (1973 a). Reactions were performed for the following soluble, coezyme-dependent oxido-reductases: glucose 6-phosphate dehydrogenase, alpha-glycerophosphate dehydrogenase, 3 alpha-hydroxysteroid dehydrogenase, NAD-as well as NADP-dependent isocitrate dehydrogenases, NAD-dependent malate dehydrogenase, NADP-dependent, decarboxylating malate dehydrogenase, uridine diphosphate glucose dehydrogenase. Measures were taken to reduce enzyme diffusion and eliminate interference from tissue tetrazolium reductases. Furthermore, reactions were performed for a number of less soluble or insoluble enzymes: glucose 6-phosphatase, mitochondrial alpha-glycerophosphate dehydrogenase, beta-hydroxybutyrate dehydrogenase, succinate dehydrogenase and tetrazolium reductases. In the proximal tubules of the female rat all enzymes studied--except beta-hydroxybutyrate dehydrogenase--showed segmental differences, most of them clearly revealing three segments. Sex differences were found concerning all enzymes except uridine diphosphate glucose dehydrogenase and NADP-dependent isocitrate dehydrogenase. The most pronounced sex-related differences were seen in the third segment in which part the male rat showed highest activity in respect to tetrazolium reductases, NAD-dependent isocitrate dehydrogenase, succinate dehydrogenase, beta-hydroxybutyrate dehydrogenase, 3 alpha-hydroxysteroid dehydrogenase and glucose 6-phosphate dehydrogenase and the female in respect to glucose 6-phosphatase, alpha-glycerophosphate dehydrogenases, and NADP-dependent, decarboxylating malate dehydrogenase. A few of the enzymes exhibited minor sex differences in the first two segments."}
{"id": "PMID:237862", "title": "Mitochondrial enzymatic adaptation of skeletal muscle to endurance training.", "content": "Some mitochondrial enzymatic activities (succinate dehydrogenase, NADH cytochrome reductase, cytochrome oxidase) were studied in the gastrocnemius and soleus muscle of the rat. The modifications of the enzyme activity, induced by endurance training, were found to be functions of 1) daily work load and 2) total training time. The treatment with an effective dose of vasodilating substances (papaverine, nicergoline, dipyridamole, and bamethan) showed that 1) nicergoline, bamethan, and dipyridamole were differently able to shorten the time of appearance of the increase in the enzymatic activities; 2) however, long-term treatments with these drugs did not prove able to modify the plateau level of the enzymatic activity increase, for a given amount of endurance training; 3) the pharmacodynamic effect on enzymatic activities was in no way related to the vasodilating effect of these drugs, since the effect was not observed with papaverine. The transition from a given level of endurance training to a lower one led to a proportional decrease of the mitochondrial enzymatic activities, thus pointing out the relation between amount of training and enzymatic activity. The drugs studied were unable to modify the decrease of enzymatic activity induced by lower work load.", "contents": "Mitochondrial enzymatic adaptation of skeletal muscle to endurance training. Some mitochondrial enzymatic activities (succinate dehydrogenase, NADH cytochrome reductase, cytochrome oxidase) were studied in the gastrocnemius and soleus muscle of the rat. The modifications of the enzyme activity, induced by endurance training, were found to be functions of 1) daily work load and 2) total training time. The treatment with an effective dose of vasodilating substances (papaverine, nicergoline, dipyridamole, and bamethan) showed that 1) nicergoline, bamethan, and dipyridamole were differently able to shorten the time of appearance of the increase in the enzymatic activities; 2) however, long-term treatments with these drugs did not prove able to modify the plateau level of the enzymatic activity increase, for a given amount of endurance training; 3) the pharmacodynamic effect on enzymatic activities was in no way related to the vasodilating effect of these drugs, since the effect was not observed with papaverine. The transition from a given level of endurance training to a lower one led to a proportional decrease of the mitochondrial enzymatic activities, thus pointing out the relation between amount of training and enzymatic activity. The drugs studied were unable to modify the decrease of enzymatic activity induced by lower work load."}
{"id": "PMID:237863", "title": "Arterial blood gases in conscious rats exposed to hypoxia, hypercapnia, or both.", "content": "Adult male rats were anesthetized and catheters were implanted in the caudal artery. Soon after recovery from short-lasting anesthesia, a total of 20 groups of six each were individually exposed to five different oxygen levels varying from 21.0 to 9.0% combined with four CO2 levels ranging from 0 to 12.9% at a mean barometric pressure of 744 Torr. Arterial blood samples were collected and analyzed for pH, Po2, and Pco2 before and near the end of 20-min exposures. During an air-breathing control period, pH averaged 7.466 plus or minus 0.020 SD, Paco2 41.2 plus or minus 1.9 Torr and Pao2 91.8 plus or minus 3.5 Torr. During hypoxia, Pao2 levels were similar to that of acutely hypoxic humans. Rats apparently differ from man in that blood buffering is greater, resulting in a higher pH during air breathing and a smaller [H-+] increase with increasing Paco2. Differences between arterial and inspired CO2 were about 10 Torr at 60 and 90 Torr Plco2 and were not influenced by Plo2.", "contents": "Arterial blood gases in conscious rats exposed to hypoxia, hypercapnia, or both. Adult male rats were anesthetized and catheters were implanted in the caudal artery. Soon after recovery from short-lasting anesthesia, a total of 20 groups of six each were individually exposed to five different oxygen levels varying from 21.0 to 9.0% combined with four CO2 levels ranging from 0 to 12.9% at a mean barometric pressure of 744 Torr. Arterial blood samples were collected and analyzed for pH, Po2, and Pco2 before and near the end of 20-min exposures. During an air-breathing control period, pH averaged 7.466 plus or minus 0.020 SD, Paco2 41.2 plus or minus 1.9 Torr and Pao2 91.8 plus or minus 3.5 Torr. During hypoxia, Pao2 levels were similar to that of acutely hypoxic humans. Rats apparently differ from man in that blood buffering is greater, resulting in a higher pH during air breathing and a smaller [H-+] increase with increasing Paco2. Differences between arterial and inspired CO2 were about 10 Torr at 60 and 90 Torr Plco2 and were not influenced by Plo2."}
{"id": "PMID:237864", "title": "Regulation of arterial PCO2 during intravenous CO2 loading.", "content": "Increased CO2 flow to the lung produced by increasing cardiac output (with constant PVCO2) results in hyperpnea with arterial PCO2 maintained at its control value (J. Appl. Physiol. 36: 457, 1974). To study if arterial PCO2 could be similarly regulated when CO2 flow was elevated by increasing PVCO2 (without changing cardiac output), we produced graded increases in PVCO2 (up to a mean of 69 mmHg) using an extracorporeal gas exchanger in five chloralose-urethan-anesthetized dogs. CO2 output increased up to fourfold. Ventilation increased in proportion to the additional CO2 flow to the lung with consequent regulation of arterial PCO2 at its control value. Comparable increases in VE produced by \"conventional\" airway loading resulted in arterial hypercapnia. The resulting CO2 response curve was similar to that found in unanesthetized dogs. We conclude that intravenous delivery of CO2 to the lung results in infinite \"sensitivity\" when computed as Delta VE/Delta paco2. These results provide evidence for a CO2-linked hyperpnea which is not mediated by measurable increases in mean arterial PCO2.", "contents": "Regulation of arterial PCO2 during intravenous CO2 loading. Increased CO2 flow to the lung produced by increasing cardiac output (with constant PVCO2) results in hyperpnea with arterial PCO2 maintained at its control value (J. Appl. Physiol. 36: 457, 1974). To study if arterial PCO2 could be similarly regulated when CO2 flow was elevated by increasing PVCO2 (without changing cardiac output), we produced graded increases in PVCO2 (up to a mean of 69 mmHg) using an extracorporeal gas exchanger in five chloralose-urethan-anesthetized dogs. CO2 output increased up to fourfold. Ventilation increased in proportion to the additional CO2 flow to the lung with consequent regulation of arterial PCO2 at its control value. Comparable increases in VE produced by \"conventional\" airway loading resulted in arterial hypercapnia. The resulting CO2 response curve was similar to that found in unanesthetized dogs. We conclude that intravenous delivery of CO2 to the lung results in infinite \"sensitivity\" when computed as Delta VE/Delta paco2. These results provide evidence for a CO2-linked hyperpnea which is not mediated by measurable increases in mean arterial PCO2."}
{"id": "PMID:237865", "title": "Renal response to secretin.", "content": "The effect of Jorpes secretin on the urinary volume, pH, and excretion of sodium, potassium, chloride, bicarbonate, titratable acidity, ammonia and phosphate was studied in five healthy male volunteers with and without simultaneous aspiration of duodenal fluids. A three- to fourfold increase in urinary volume and sodium excretion occurred within the first 30 min after secretin injection and this was accompanied by a significant rise in urinary pH in each instance. Urinary bicarbonate excretion increased from 55 plus or minus 13 to 395 plus or minus 33 mueq/30 min after secretin injection. Aspiration of alkaline duodenal contents was accompanied by an even greater postsecretin increase in urinary bicarbonate excretion. No significant changes in arterial pH or blood gases were detected throughout the study. These observations are compatible with a direct effect of secretin upon the renal tubular reabsorption of water, bicarbonate, and other ions, and could account for the transient alterations in urinary pH occurring in response to a meal.", "contents": "Renal response to secretin. The effect of Jorpes secretin on the urinary volume, pH, and excretion of sodium, potassium, chloride, bicarbonate, titratable acidity, ammonia and phosphate was studied in five healthy male volunteers with and without simultaneous aspiration of duodenal fluids. A three- to fourfold increase in urinary volume and sodium excretion occurred within the first 30 min after secretin injection and this was accompanied by a significant rise in urinary pH in each instance. Urinary bicarbonate excretion increased from 55 plus or minus 13 to 395 plus or minus 33 mueq/30 min after secretin injection. Aspiration of alkaline duodenal contents was accompanied by an even greater postsecretin increase in urinary bicarbonate excretion. No significant changes in arterial pH or blood gases were detected throughout the study. These observations are compatible with a direct effect of secretin upon the renal tubular reabsorption of water, bicarbonate, and other ions, and could account for the transient alterations in urinary pH occurring in response to a meal."}
{"id": "PMID:237866", "title": "Effects of moderate hypoxemia and hypocapnia on CSF [H+] and ventilation in man.", "content": "The effects of 26 h of normoxic hypocapnia (PaCO2, 31 MMHg) vs. 26 h of hypocapnia plus hypobaric hypoxia (PaCO2 32, PaO2 57 mmHg) were compared with respect to: a) CSF acid-base status; and b) the spontaneous ventilation (at PIO2 145 mmHg) which followed the imposed (voluntary) hyperventilation. For each condition of prolonged hypocapnia, PaCO2 was held constant throughout and pHa and [HCO3-]a were constant over the final 6-10 h. We assumed that measured changes in lumbar CSF acid-base status paralleled those in cisternal CSF. Spontaneous hyperventilation followed both normoxic and hypoxic hypocapnia but was significantly greater following hypoxic hypocapnia. In the CSF, pH compensation after 26 h of hyperventilation was incomplete (similar to 45-50%), was similar to that in arterial blood, and was unaffected by a superimposed hypoxemia. These data were inconsistent with current theory which proposes the regulation of CSF [HCO2] via local mechanisms and, in turn, the mediation of ventilatory acclimatization to hypoxemia and/or hypocapnia via CSF [H+]. Alternative mediators of ventilatory acclimatization were postulated, including mechanisms both dependent on and independent of \"chemoreceptor\" stimuli.", "contents": "Effects of moderate hypoxemia and hypocapnia on CSF [H+] and ventilation in man. The effects of 26 h of normoxic hypocapnia (PaCO2, 31 MMHg) vs. 26 h of hypocapnia plus hypobaric hypoxia (PaCO2 32, PaO2 57 mmHg) were compared with respect to: a) CSF acid-base status; and b) the spontaneous ventilation (at PIO2 145 mmHg) which followed the imposed (voluntary) hyperventilation. For each condition of prolonged hypocapnia, PaCO2 was held constant throughout and pHa and [HCO3-]a were constant over the final 6-10 h. We assumed that measured changes in lumbar CSF acid-base status paralleled those in cisternal CSF. Spontaneous hyperventilation followed both normoxic and hypoxic hypocapnia but was significantly greater following hypoxic hypocapnia. In the CSF, pH compensation after 26 h of hyperventilation was incomplete (similar to 45-50%), was similar to that in arterial blood, and was unaffected by a superimposed hypoxemia. These data were inconsistent with current theory which proposes the regulation of CSF [HCO2] via local mechanisms and, in turn, the mediation of ventilatory acclimatization to hypoxemia and/or hypocapnia via CSF [H+]. Alternative mediators of ventilatory acclimatization were postulated, including mechanisms both dependent on and independent of \"chemoreceptor\" stimuli."}
{"id": "PMID:237867", "title": "Effects of CO-2 and extracellular H+ iontophoresis on single cell activity in the cat brainstem.", "content": "The activity of single cells in deep regions of the medulla oblongata was observed both during CO2 inhalation and during the extracellular iontophoresis of hydrogen ions in peripheral chemoreceptor-denervated cats. All 53 neurons that fired in synchrony with some part of the ventilatory cycle showed increased firing during CO2 inhalation; yet none responded in a graded fashion to the extracellular application of hydrogen ions. Seventy-one of the 74 nonperiodic cells studied showed no response to CO2 inhalation. Of the 3 nonperiodic cells that did respond to CO2, 2 also responded in a graded fashion to the extracellular iontophoresis of hydrogen ions. It is concluded that the cell bodies of medullary neurons with respiratory periodicity are relatively insensitive to hydrogen ions. Further the paucity of hydrogen ion-sensitive cells found in deep areas of the medulla does not support the notion that medullary hydrogen ion chemoreception is largely achieved by structures located deep in the lower brainstem.", "contents": "Effects of CO-2 and extracellular H+ iontophoresis on single cell activity in the cat brainstem. The activity of single cells in deep regions of the medulla oblongata was observed both during CO2 inhalation and during the extracellular iontophoresis of hydrogen ions in peripheral chemoreceptor-denervated cats. All 53 neurons that fired in synchrony with some part of the ventilatory cycle showed increased firing during CO2 inhalation; yet none responded in a graded fashion to the extracellular application of hydrogen ions. Seventy-one of the 74 nonperiodic cells studied showed no response to CO2 inhalation. Of the 3 nonperiodic cells that did respond to CO2, 2 also responded in a graded fashion to the extracellular iontophoresis of hydrogen ions. It is concluded that the cell bodies of medullary neurons with respiratory periodicity are relatively insensitive to hydrogen ions. Further the paucity of hydrogen ion-sensitive cells found in deep areas of the medulla does not support the notion that medullary hydrogen ion chemoreception is largely achieved by structures located deep in the lower brainstem."}
{"id": "PMID:237868", "title": "Time course of exchanges between red cells and extracellular fluid during CO2 uptake.", "content": "A stopped-flow rapid-reaction apparatus was used to follow the time course of extracellular pH in a human red cell suspension following a sudden increase in PCO2. The extracellular pH change was slow (t1/2 similar to 3.5 s) considering the presence of carbonic anhydrase in the cells. When carbonic anhydrase was added to the extracellular fluid, the half-time was reduced to less than 20 ms. The explanation for these phenomena is that the equilibration of H+ across the red cell membrane is rate-limited by the uncatalyzed reaction CO2 plus H2O formed from H2CO3 outside the cells. A theoretical model was developed which successfully reproduced the experimental results. When the model was used to simulate CO2 exchange in vivo, it was determined that blood PCO2 and pH require long times (greater than 50 s) to approach equilibrium between cells and plasma after leaving an exchange capillary. We conclude that cell-plasma equilibrium may never be reached in vivo, and that in vitro measurements of these quantities may not represent their true values at the site of sampling.", "contents": "Time course of exchanges between red cells and extracellular fluid during CO2 uptake. A stopped-flow rapid-reaction apparatus was used to follow the time course of extracellular pH in a human red cell suspension following a sudden increase in PCO2. The extracellular pH change was slow (t1/2 similar to 3.5 s) considering the presence of carbonic anhydrase in the cells. When carbonic anhydrase was added to the extracellular fluid, the half-time was reduced to less than 20 ms. The explanation for these phenomena is that the equilibration of H+ across the red cell membrane is rate-limited by the uncatalyzed reaction CO2 plus H2O formed from H2CO3 outside the cells. A theoretical model was developed which successfully reproduced the experimental results. When the model was used to simulate CO2 exchange in vivo, it was determined that blood PCO2 and pH require long times (greater than 50 s) to approach equilibrium between cells and plasma after leaving an exchange capillary. We conclude that cell-plasma equilibrium may never be reached in vivo, and that in vitro measurements of these quantities may not represent their true values at the site of sampling."}
{"id": "PMID:237869", "title": "Incomplete compensation of CSF [H+] in man during acclimatization to high altitude (48300 M).", "content": "This study has assessed the regulation of arterial blood and cerebrospinal fluid acid-base status in seven healthy men, at 250 m altitude and after 5 and 10-11 days sojourn at 4,300 m altitude (PaO2 = 39 mmHg day 1 to 48 mmHg day 11). We assumed that observed changes in lumbar spinal fluid acid-base status paralleled those in cisternal CSF, under these relatively steady-state conditions. Ventilatory acclimatization during the sojourn (-14 mmHg PaCO2 at day 11) was accompanied by: 1) reductions in [HCO3-] (-5 to -7 meq/1) which were similar in arterial blood and CSF; 2) substantial, yet incomplete, compensation (70-75%) of both CSF and blood pH; and 3) a level of CSF pH which was maintained significantly alkaline (+0.05 +/- 0.01) to normoxic control values. These data at 4,300 m confirmed and extended our previous findings for more moderate conditions of chronic hypoxia. It was postulated that the magnitude and time course of pH compensation in the CSF during chronic hypoxia and/or hypocapnia are determined by corresponding changes in plasma [HCO2-].", "contents": "Incomplete compensation of CSF [H+] in man during acclimatization to high altitude (48300 M). This study has assessed the regulation of arterial blood and cerebrospinal fluid acid-base status in seven healthy men, at 250 m altitude and after 5 and 10-11 days sojourn at 4,300 m altitude (PaO2 = 39 mmHg day 1 to 48 mmHg day 11). We assumed that observed changes in lumbar spinal fluid acid-base status paralleled those in cisternal CSF, under these relatively steady-state conditions. Ventilatory acclimatization during the sojourn (-14 mmHg PaCO2 at day 11) was accompanied by: 1) reductions in [HCO3-] (-5 to -7 meq/1) which were similar in arterial blood and CSF; 2) substantial, yet incomplete, compensation (70-75%) of both CSF and blood pH; and 3) a level of CSF pH which was maintained significantly alkaline (+0.05 +/- 0.01) to normoxic control values. These data at 4,300 m confirmed and extended our previous findings for more moderate conditions of chronic hypoxia. It was postulated that the magnitude and time course of pH compensation in the CSF during chronic hypoxia and/or hypocapnia are determined by corresponding changes in plasma [HCO2-]."}
{"id": "PMID:237870", "title": "Distribution of ventilation-perfusion ratios in dogs with normal and abnormal lungs.", "content": "We have recently described a new method for measuring distributions of ventilation-perfusion ratios (VA/Q) based on inert gas elimination. Here we report the initial application of the method in normal dogs and in dogs with pulmonary embolism, pulmonary edema, and pneumonia. Characteristic distributions appropriate to the known effects of each lesion were observed. Comparison with traditional indices of gas exchange revealed that the arterial PO2 calculated from the distributions agreed  well with measured values, as did the shunts indicated by the method and by the arterial PO2 while breathing 100 per cent 02. Also the Bohr dead space closely matched the dispersion of ventilation in realtion to VA/Q. Assumptions made in the method were critically evaluated and appear justified. These include the existence of a steady state of gas exchange, an alveolar-end-capillary diffusion equilibration, and the fact that all of the observered VA/Q inequality occurs between gas exchange units in parallel. However, theoretical analysis suggests that the method can detect failure of diffusion equilbration across the blood-gas barrier should it exist. These results suggest that the method is well-suited to clinical investigation of patients with pulmonary disease.", "contents": "Distribution of ventilation-perfusion ratios in dogs with normal and abnormal lungs. We have recently described a new method for measuring distributions of ventilation-perfusion ratios (VA/Q) based on inert gas elimination. Here we report the initial application of the method in normal dogs and in dogs with pulmonary embolism, pulmonary edema, and pneumonia. Characteristic distributions appropriate to the known effects of each lesion were observed. Comparison with traditional indices of gas exchange revealed that the arterial PO2 calculated from the distributions agreed  well with measured values, as did the shunts indicated by the method and by the arterial PO2 while breathing 100 per cent 02. Also the Bohr dead space closely matched the dispersion of ventilation in realtion to VA/Q. Assumptions made in the method were critically evaluated and appear justified. These include the existence of a steady state of gas exchange, an alveolar-end-capillary diffusion equilibration, and the fact that all of the observered VA/Q inequality occurs between gas exchange units in parallel. However, theoretical analysis suggests that the method can detect failure of diffusion equilbration across the blood-gas barrier should it exist. These results suggest that the method is well-suited to clinical investigation of patients with pulmonary disease."}
{"id": "PMID:237871", "title": "Saturation dependency of the Bohr effect: interactions among H-+, CO2, and DPG.", "content": "The Bohr effect was measured in normal whole blood and in blood with low DPG concentration as a function of oxygen saturation. pH was changed by varying CO2 concentration (CO2 Bohr effect) or by addition of isotonic NaOH or HC1 at constant PCO2 (fixed acid Bohr effect). At nornal DPG concentration CO2 Bohr effect was -0.52 at 50% blood oxygen saturation, increasing in magnitude at lower saturation and decreasing in magnitude at higher saturation. In DPG depleted blood with base excess (BE) similar to 0 meq/1, there was similar dependence of CO2 Bohr effect on oxygen saturation. At BE similar to -10 meq/1, influence of saturation was comparable, but the magnitude of the Bohr effect was markedly increased at all saturations. Fixed acid Bohr effect at normal DPG concentration was -0.45 at saturations of 50-90% but decreased at lower saturations. In DPG-depleted blood fixed acid Bohr effect averaged about -0.33 with minimal variation with saturation. Influence of DPG on oxygen affinity was greater at intermediate saturations and less at saturations below 20% and above 80%. Effect of CO2, independent of pH, was many fold greater at lower oxygen saturations than at higher saturations. These results support the suggestion that the alpha chain of hemoglobin is the site of the initial oxygenation reaction. Physiologically they indicate that the relative contribution of CO2 and fixed acid, as well as the level of oxygen saturation and DPG concentration, may be important in determining PO2 of capillary blood and resulting oxygen delivery.", "contents": "Saturation dependency of the Bohr effect: interactions among H-+, CO2, and DPG. The Bohr effect was measured in normal whole blood and in blood with low DPG concentration as a function of oxygen saturation. pH was changed by varying CO2 concentration (CO2 Bohr effect) or by addition of isotonic NaOH or HC1 at constant PCO2 (fixed acid Bohr effect). At nornal DPG concentration CO2 Bohr effect was -0.52 at 50% blood oxygen saturation, increasing in magnitude at lower saturation and decreasing in magnitude at higher saturation. In DPG depleted blood with base excess (BE) similar to 0 meq/1, there was similar dependence of CO2 Bohr effect on oxygen saturation. At BE similar to -10 meq/1, influence of saturation was comparable, but the magnitude of the Bohr effect was markedly increased at all saturations. Fixed acid Bohr effect at normal DPG concentration was -0.45 at saturations of 50-90% but decreased at lower saturations. In DPG-depleted blood fixed acid Bohr effect averaged about -0.33 with minimal variation with saturation. Influence of DPG on oxygen affinity was greater at intermediate saturations and less at saturations below 20% and above 80%. Effect of CO2, independent of pH, was many fold greater at lower oxygen saturations than at higher saturations. These results support the suggestion that the alpha chain of hemoglobin is the site of the initial oxygenation reaction. Physiologically they indicate that the relative contribution of CO2 and fixed acid, as well as the level of oxygen saturation and DPG concentration, may be important in determining PO2 of capillary blood and resulting oxygen delivery."}
{"id": "PMID:237872", "title": "A simplified method for determining the P50 of blood.", "content": "A method  to determine the P50 of whole blood is described using a modified American Optical reflectance oximeter, pump, and membrane tonometer, together with PO2, PCO2, and pH measurements in a standard blood gas machine. Determinations of P50 were made in 66 patients and normal subjects and in two situations where P50 was very low and very high. The results were compared to oxygen saturations  calculated from measured oxygen content. The directly determined oxygen saturation agreed with the assumed saturation of 50 per cent in the oximeter within 0.5 per cent. The apparatus appears to be a simple and relatively inexpensive method to obtain P50 as long as blood carboxyhemoglobin or methemoglobin contents are not elevated.", "contents": "A simplified method for determining the P50 of blood. A method  to determine the P50 of whole blood is described using a modified American Optical reflectance oximeter, pump, and membrane tonometer, together with PO2, PCO2, and pH measurements in a standard blood gas machine. Determinations of P50 were made in 66 patients and normal subjects and in two situations where P50 was very low and very high. The results were compared to oxygen saturations  calculated from measured oxygen content. The directly determined oxygen saturation agreed with the assumed saturation of 50 per cent in the oximeter within 0.5 per cent. The apparatus appears to be a simple and relatively inexpensive method to obtain P50 as long as blood carboxyhemoglobin or methemoglobin contents are not elevated."}
{"id": "PMID:237873", "title": "Colorimetric assay of strychnine and brucine in nux vomica.", "content": "Two colorimetric methods are described for the estimation of strychnine and brucine in nux vomica. The first is a modification of the Karawya and Ghourab method for the determination of strychnine, in which the sensitivity of the color is increased by changing certain conditions of the method. The second was developed for the determination of brucine and is based on measuring the intensity of the violet color produced by treating brucine with nitric acid and methanolic stannous chloride. In the presence of large amounts of strychnine, brucine is isolated prior to colorimetric analysis by a quantitative thin layer chromatographic technique.", "contents": "Colorimetric assay of strychnine and brucine in nux vomica. Two colorimetric methods are described for the estimation of strychnine and brucine in nux vomica. The first is a modification of the Karawya and Ghourab method for the determination of strychnine, in which the sensitivity of the color is increased by changing certain conditions of the method. The second was developed for the determination of brucine and is based on measuring the intensity of the violet color produced by treating brucine with nitric acid and methanolic stannous chloride. In the presence of large amounts of strychnine, brucine is isolated prior to colorimetric analysis by a quantitative thin layer chromatographic technique."}
{"id": "PMID:237874", "title": "Determination of procaine and related local anesthetics. I. Partition chromatographic separation and assay of mixtures of procaine with tetracaine and with propoxycaine.", "content": "Determination of ionization and extraction constants for procaine, tetracaine, and propoxycaine led to selection of a simple partition chromatographic system for separation and assay of mixtures of these anesthetics. A 65% solution of chloroform in isooctane elutes tetracaine or propoxycaine from a pH 4:sodium bromide column; procaine is retained and subsequently eluted by chloroform as the bromide ion-pair. The anesthetics are then determined spectrophotometrically. Results of assay of standard and commercial formulations are presented.", "contents": "Determination of procaine and related local anesthetics. I. Partition chromatographic separation and assay of mixtures of procaine with tetracaine and with propoxycaine. Determination of ionization and extraction constants for procaine, tetracaine, and propoxycaine led to selection of a simple partition chromatographic system for separation and assay of mixtures of these anesthetics. A 65% solution of chloroform in isooctane elutes tetracaine or propoxycaine from a pH 4:sodium bromide column; procaine is retained and subsequently eluted by chloroform as the bromide ion-pair. The anesthetics are then determined spectrophotometrically. Results of assay of standard and commercial formulations are presented."}
{"id": "PMID:237875", "title": "Determination of potassium guaiacolsulfonate by ion-pairing partition chromatography.", "content": "Potassium guaiacolsulfonate, a highly polar, acidic substance, is readily eluted by chloroform from a pH 4.5 Celite column in the form of its ion-pair with trihexylamine, thereby effecting facile separation from other pharmaceuticals. The sulfonic acid is then back-extracted into aqueous alkali and determined spectrophotometrically. Assay of standard solutions by this procedre averaged 100.44 plus or minus 0.81%. The method was applied successfully to 4 commercial cough preparations containing a variety of other drugs.", "contents": "Determination of potassium guaiacolsulfonate by ion-pairing partition chromatography. Potassium guaiacolsulfonate, a highly polar, acidic substance, is readily eluted by chloroform from a pH 4.5 Celite column in the form of its ion-pair with trihexylamine, thereby effecting facile separation from other pharmaceuticals. The sulfonic acid is then back-extracted into aqueous alkali and determined spectrophotometrically. Assay of standard solutions by this procedre averaged 100.44 plus or minus 0.81%. The method was applied successfully to 4 commercial cough preparations containing a variety of other drugs."}
{"id": "PMID:237876", "title": "Mycotoxin bioassay, using Bacillus stearothermophilus.", "content": "Spores of Bacillus stearothermophilus in standardized spore strips are pretreated with solutions of the mycotoxins aflatoxin B1, patulin, rubratoxin B, and diacetoxyscirpenol and subsequently incubated in a nutrient solution containing bromocresol purple as pH indicator. After 16.5 hr of inclubation the color of the indicator medium inoculated with untreated spore strips of B. stearothermophilus changes from purple to yellow; no color change occurs in the indicator medium inoculated with spore strips treated 15 min with 0.01 mug of any of the 4 mycotoxins/ml during a 60 hr incubation.", "contents": "Mycotoxin bioassay, using Bacillus stearothermophilus. Spores of Bacillus stearothermophilus in standardized spore strips are pretreated with solutions of the mycotoxins aflatoxin B1, patulin, rubratoxin B, and diacetoxyscirpenol and subsequently incubated in a nutrient solution containing bromocresol purple as pH indicator. After 16.5 hr of inclubation the color of the indicator medium inoculated with untreated spore strips of B. stearothermophilus changes from purple to yellow; no color change occurs in the indicator medium inoculated with spore strips treated 15 min with 0.01 mug of any of the 4 mycotoxins/ml during a 60 hr incubation."}
{"id": "PMID:237877", "title": "Factors in the diagnosis and treatment of chronic pain.", "content": "Symptoms are the verbal and nonverbal communicative expressions of experience. At any one time, the symptom is dependent on structural changes, genetic variations, metabolic abnormalities, immunopathic and other disorders, and the totality of social, economic, and situational experience. Complaints of pain may vary with time depending on the interaction of these features in a manner not directly related to the intensity of a noxious stimulus.", "contents": "Factors in the diagnosis and treatment of chronic pain. Symptoms are the verbal and nonverbal communicative expressions of experience. At any one time, the symptom is dependent on structural changes, genetic variations, metabolic abnormalities, immunopathic and other disorders, and the totality of social, economic, and situational experience. Complaints of pain may vary with time depending on the interaction of these features in a manner not directly related to the intensity of a noxious stimulus."}
{"id": "PMID:237878", "title": "Purification and properties of the glutathione reductase of Chromatium vinosum.", "content": "The Chromatium vinosum glutathione reductase [NAD(P)H: glutathione disulfide oxidoreductase, EC 1.6.4.2] was purified to apparent homogeneity. The enzyme was found to require reduced nicotinamide adenine dinucleotide (NADH) as a reductant and to be specific for oxidized glutathione (GSSG). The polypeptide molecular weight in sodium dodecyl sulfate was found to be 52,000. Incubation of enzyme with NADH in the absence of GSSG resulted in a significant loss in activity. The enzyme was stimulated by phosphate and sulfate ion, but was inhibited by chloride ion, heavy metals, and sulfhydryl reagents. Adenylate nucleotides were inhibitory, and the data suggested that they were acting as competitive inhibitors of flavin adenine dinucleotide (FAD). The Km values of 7 X 10-3 for GSSG and 6 X 10-5 M for NADH were the highest reported of any previously investigated glutathione reductase. The order of addition of components markedly affected the response of the enzyme to FAD. A requirement for FAD (Km 5.2 X 10-7 M) was seen if the enzyme was incubated with NADH prior to GSSG addition, whereas no FAD was required if the order was reversed.", "contents": "Purification and properties of the glutathione reductase of Chromatium vinosum. The Chromatium vinosum glutathione reductase [NAD(P)H: glutathione disulfide oxidoreductase, EC 1.6.4.2] was purified to apparent homogeneity. The enzyme was found to require reduced nicotinamide adenine dinucleotide (NADH) as a reductant and to be specific for oxidized glutathione (GSSG). The polypeptide molecular weight in sodium dodecyl sulfate was found to be 52,000. Incubation of enzyme with NADH in the absence of GSSG resulted in a significant loss in activity. The enzyme was stimulated by phosphate and sulfate ion, but was inhibited by chloride ion, heavy metals, and sulfhydryl reagents. Adenylate nucleotides were inhibitory, and the data suggested that they were acting as competitive inhibitors of flavin adenine dinucleotide (FAD). The Km values of 7 X 10-3 for GSSG and 6 X 10-5 M for NADH were the highest reported of any previously investigated glutathione reductase. The order of addition of components markedly affected the response of the enzyme to FAD. A requirement for FAD (Km 5.2 X 10-7 M) was seen if the enzyme was incubated with NADH prior to GSSG addition, whereas no FAD was required if the order was reversed."}
{"id": "PMID:237879", "title": "Identification of a deoxyribonuclease implicated in genetic transformation of Diplococcus pneumoniae.", "content": "A mutation of Diplococcus pneumoniae, end-1, reduces the major deoxyribonuclease activity of the cell, an endonuclease, to 10% of its normal value without impairing transformation. Further mutations, called noz, abolish the residual endonuclease activity and block transformation. The residual endonuclease is similar to the wild-type enzyme in size, charge, divalent cation dependence, inhibition by ribonucleic acid, and formation of oligonucleotide products. However, the mutant endonuclease is more temperature sensitive, which suggests that the end-1 mutation occurred in a structural gene for the enzyme. Genetic analysis showed that the noz mutations occur at the same genetic locus. A number of new end mutants were analyzed. Those that retained more than 1.4% of the normal endonuclease activity were essentially normal in transformation; those with less than 1% were defective. The transformation-defective end mutants appear to be blocked in the entry of deoxyribonucleic acid (DNA) since they carry out the prior step of binding DNA to the outside of the cell. The major endonuclease of the cell may act as a DNA translocase by attacking and degrading one strand of DNA, thereby facilitating entry of the complementary strand into the cell.", "contents": "Identification of a deoxyribonuclease implicated in genetic transformation of Diplococcus pneumoniae. A mutation of Diplococcus pneumoniae, end-1, reduces the major deoxyribonuclease activity of the cell, an endonuclease, to 10% of its normal value without impairing transformation. Further mutations, called noz, abolish the residual endonuclease activity and block transformation. The residual endonuclease is similar to the wild-type enzyme in size, charge, divalent cation dependence, inhibition by ribonucleic acid, and formation of oligonucleotide products. However, the mutant endonuclease is more temperature sensitive, which suggests that the end-1 mutation occurred in a structural gene for the enzyme. Genetic analysis showed that the noz mutations occur at the same genetic locus. A number of new end mutants were analyzed. Those that retained more than 1.4% of the normal endonuclease activity were essentially normal in transformation; those with less than 1% were defective. The transformation-defective end mutants appear to be blocked in the entry of deoxyribonucleic acid (DNA) since they carry out the prior step of binding DNA to the outside of the cell. The major endonuclease of the cell may act as a DNA translocase by attacking and degrading one strand of DNA, thereby facilitating entry of the complementary strand into the cell."}
{"id": "PMID:237880", "title": "Effect of pH and biotin on a circadian rhyythm of conidiation in Neurospora crassa.", "content": "Expression of a circadian rhythm of conidiation in Neurospora crassa is enhanced in cultures grown on medium that is neutral or deficient in biotin.", "contents": "Effect of pH and biotin on a circadian rhyythm of conidiation in Neurospora crassa. Expression of a circadian rhythm of conidiation in Neurospora crassa is enhanced in cultures grown on medium that is neutral or deficient in biotin."}
{"id": "PMID:237881", "title": "Glucose transport in Acholeplasma laidlawii B: dependence on the fluidity and physical state of membrane lipids.", "content": "The uptake of D-glucose by Acholeplasma laidlawii B occurs via a mediated transport process, as shown by the following observations: (i) glucose permeates A. laidlawii B cells at a rate at least 100 times greater than would be expected if its entry occurred only by simple passive diffusion; (ii) the apparent activation energy for glucose uptake in A. laidlawii is significantly lower than that expected and observed for the passive permeation of this sugar; (iii) glucose uptake appears to be a saturable process; (iv) glucose uptake can be completely inhibited by low concentrations of phloretin and phlorizin; and (v) glucose uptake is markedly inhibited at temperatures above 45 C, whereas the passive entry of erythritol continues to increase logarithmically until at least 60 C. The metabolism of D-glucose by this organism is rapid and, at low glucose concentrations, the intracellular radioactivity derived from D-[14-C]glucose is at any given time a reflection of the net effect of glucose transport, glucose metabolism, and loss from the cell of radioactive metabolic products. Care must thus be taken when attempting to determine the rate of glucose transport by measuring the accumulation by the cells of the total radioactivity derived from D-[14-C]glucose. The rate of uptake of D-glucose by A. laidlawii B cells is markedly dependent on the fatty acid composition and cholesterol content of the plasma membrane and exhibits a direct dependence on the fluidity of the membrane lipids as measured by their reversible, thermotropic gel to liquie-crystalline phase transition temperatures. In contrast to the transport rates, the apparent activation energy for glucose uptake above the phase transition temperature is not dependent on membrane lipid composition. At the temperature range within the membrane lipid phase transition region, the apparent activation energy of glucose uptake is different from the activation energy observed at temperatures above the phase transition. This may reflect the superimposed operation within the phase transition region of more than one temperature-dependent process.", "contents": "Glucose transport in Acholeplasma laidlawii B: dependence on the fluidity and physical state of membrane lipids. The uptake of D-glucose by Acholeplasma laidlawii B occurs via a mediated transport process, as shown by the following observations: (i) glucose permeates A. laidlawii B cells at a rate at least 100 times greater than would be expected if its entry occurred only by simple passive diffusion; (ii) the apparent activation energy for glucose uptake in A. laidlawii is significantly lower than that expected and observed for the passive permeation of this sugar; (iii) glucose uptake appears to be a saturable process; (iv) glucose uptake can be completely inhibited by low concentrations of phloretin and phlorizin; and (v) glucose uptake is markedly inhibited at temperatures above 45 C, whereas the passive entry of erythritol continues to increase logarithmically until at least 60 C. The metabolism of D-glucose by this organism is rapid and, at low glucose concentrations, the intracellular radioactivity derived from D-[14-C]glucose is at any given time a reflection of the net effect of glucose transport, glucose metabolism, and loss from the cell of radioactive metabolic products. Care must thus be taken when attempting to determine the rate of glucose transport by measuring the accumulation by the cells of the total radioactivity derived from D-[14-C]glucose. The rate of uptake of D-glucose by A. laidlawii B cells is markedly dependent on the fatty acid composition and cholesterol content of the plasma membrane and exhibits a direct dependence on the fluidity of the membrane lipids as measured by their reversible, thermotropic gel to liquie-crystalline phase transition temperatures. In contrast to the transport rates, the apparent activation energy for glucose uptake above the phase transition temperature is not dependent on membrane lipid composition. At the temperature range within the membrane lipid phase transition region, the apparent activation energy of glucose uptake is different from the activation energy observed at temperatures above the phase transition. This may reflect the superimposed operation within the phase transition region of more than one temperature-dependent process."}
{"id": "PMID:237882", "title": "Phosphorylation of solubilized sarcoplasmic reticulum by orthophosphate and its thermodynamic characteristics. The dominant role of entropy in the phosphorylation.", "content": "A large fraction of the Ca-2plus- and Mg-2plus-dependent ATPase (EC 3.6.1.3) in sarcoplasmic reticulum membranes solubilized with Triton X-100 was phosphorylated with Pi. The phosphorylation required Mg-2plus but was strongly inhibited by low concentrations of Ca-2plus. A Ca-2plus ion concentration of 30 muM caused half-maximum inhibition in the presence of 50 mM MgCl2. The phosphorylated enzyme showed a rapid turnover and was in dynamic equilibrium with Pi in the medium. At equilibrium the amount of the phosphorylated enzyme increased markedly with increased in the reaction temperature. The apparent standard free energy change, the apparent standard enthalpy change, and the apparent standard entropy change in the formation of the phosphorylated enzyme from the enzyme-phosphate complex in the presence of excess Mg-2plus at 37 degrees and pH 7.0 were, respectively, 0.35 Cal per mol, 15.9 Cal per mol, and 50.2 e.u. per mol. The susceptibility of the acid-denatured phosphorylated enzyme to hydroxylamine showed that the phosphorylated enzyme is of an acyl phosphate type. The present results are consistent with the probability that the phosphorylation results from reversal of late steps in the Ca-2plus transport process. The results clearly show that the phosphorylated enzyme is stabilized by a great increase in entropy upon its formation from the enzyme-phosphate complex.", "contents": "Phosphorylation of solubilized sarcoplasmic reticulum by orthophosphate and its thermodynamic characteristics. The dominant role of entropy in the phosphorylation. A large fraction of the Ca-2plus- and Mg-2plus-dependent ATPase (EC 3.6.1.3) in sarcoplasmic reticulum membranes solubilized with Triton X-100 was phosphorylated with Pi. The phosphorylation required Mg-2plus but was strongly inhibited by low concentrations of Ca-2plus. A Ca-2plus ion concentration of 30 muM caused half-maximum inhibition in the presence of 50 mM MgCl2. The phosphorylated enzyme showed a rapid turnover and was in dynamic equilibrium with Pi in the medium. At equilibrium the amount of the phosphorylated enzyme increased markedly with increased in the reaction temperature. The apparent standard free energy change, the apparent standard enthalpy change, and the apparent standard entropy change in the formation of the phosphorylated enzyme from the enzyme-phosphate complex in the presence of excess Mg-2plus at 37 degrees and pH 7.0 were, respectively, 0.35 Cal per mol, 15.9 Cal per mol, and 50.2 e.u. per mol. The susceptibility of the acid-denatured phosphorylated enzyme to hydroxylamine showed that the phosphorylated enzyme is of an acyl phosphate type. The present results are consistent with the probability that the phosphorylation results from reversal of late steps in the Ca-2plus transport process. The results clearly show that the phosphorylated enzyme is stabilized by a great increase in entropy upon its formation from the enzyme-phosphate complex."}
{"id": "PMID:237883", "title": "Purification and characterization of mouse hypoxanthine-guanine phosphoribosyltransferase.", "content": "Hypoxanthine-guanine phosphoribosyltransferase (HGPR transferase) (EC 2.4.2.8) has been purified approximately 4500-fold to apparent homogeneity from mouse liver. The procedure involves the use of affinity chromatography and was designed to be readily adaptable to small scale isolations. The enzyme appears to be composed of 3 subunits of identical molecular weight (27,000 per subunit). The subunit molecular weight has also been determined by the analysis of radioactively labeled HGPR transferase immunoprecipitated from wild type and mutant (HGPR transferase) mouse tissue culture cell lines.", "contents": "Purification and characterization of mouse hypoxanthine-guanine phosphoribosyltransferase. Hypoxanthine-guanine phosphoribosyltransferase (HGPR transferase) (EC 2.4.2.8) has been purified approximately 4500-fold to apparent homogeneity from mouse liver. The procedure involves the use of affinity chromatography and was designed to be readily adaptable to small scale isolations. The enzyme appears to be composed of 3 subunits of identical molecular weight (27,000 per subunit). The subunit molecular weight has also been determined by the analysis of radioactively labeled HGPR transferase immunoprecipitated from wild type and mutant (HGPR transferase) mouse tissue culture cell lines."}
{"id": "PMID:237884", "title": "Threonine deaminase from Escherichia coli. II. Maturation and physical properties of the enzyme from a mutant altered in its regulation of gene expression.", "content": "The biosynthetic L-threonine deaminase (L-threonine hydrolase deaminating, EC 4.2.1.16) has been purified from Escherichia coli K12 regulatory mutant CU18. This mutant has properties that follow the predictions of the autogregulatory model previously proposed for the control of synthesis of the isoleucine-valine biosynthetic enzymes. The autoregulatory model specifies that L-threonine deaminase participates in the control of the expression of the ilv ADE gene cluster as well as the ilv B gene and ilv C gene, which constitute three separate units of regulation. The single mutation in strain CU18 results in altered regulation of ilv gene expression and in the production of an altered L-threonine deaminase. The immature form of the enzyme purified from mutant CU18 exhibits an altered response to L-valine, a maturation-inducing ligand. The native form of the mutant is altered in its apparent Km for L-threonine and in its response to the effects of L-valine and L-isoleucine upon catalytic activity. The mutant and wild type L-threonine deaminases differ in the apoenzyme formed as a consequence of alkaline dialysis. Dialysis of the mutant enzyme yields an apoenzyme mixture, apparently of dimers and monomers, while the wild type enzyme yields only dimers. The CU18 L-threonine deaminase, is however, indistinguishable from the wild type enzyme in molecular weight and subunit composition.", "contents": "Threonine deaminase from Escherichia coli. II. Maturation and physical properties of the enzyme from a mutant altered in its regulation of gene expression. The biosynthetic L-threonine deaminase (L-threonine hydrolase deaminating, EC 4.2.1.16) has been purified from Escherichia coli K12 regulatory mutant CU18. This mutant has properties that follow the predictions of the autogregulatory model previously proposed for the control of synthesis of the isoleucine-valine biosynthetic enzymes. The autoregulatory model specifies that L-threonine deaminase participates in the control of the expression of the ilv ADE gene cluster as well as the ilv B gene and ilv C gene, which constitute three separate units of regulation. The single mutation in strain CU18 results in altered regulation of ilv gene expression and in the production of an altered L-threonine deaminase. The immature form of the enzyme purified from mutant CU18 exhibits an altered response to L-valine, a maturation-inducing ligand. The native form of the mutant is altered in its apparent Km for L-threonine and in its response to the effects of L-valine and L-isoleucine upon catalytic activity. The mutant and wild type L-threonine deaminases differ in the apoenzyme formed as a consequence of alkaline dialysis. Dialysis of the mutant enzyme yields an apoenzyme mixture, apparently of dimers and monomers, while the wild type enzyme yields only dimers. The CU18 L-threonine deaminase, is however, indistinguishable from the wild type enzyme in molecular weight and subunit composition."}
{"id": "PMID:237885", "title": "Nicotinamide adenine dinucleotide phosphate-malic enzyme of rat liver. Purification, properties, and immunochemical studies.", "content": "Rat liver malic enzyme (EC 1.1.1.40) was purified from livers of rats fasted and refed a high sucrose diet containing 1% desiccated thyroid powder. The purification was accomplished by a six-step procedure. The specific activity of the purified enzyme was increased 181-fold above that of the initial high speed supernatant of liver extracts. Slight additional purification of malic enzyme was achieved with preparative disc electrophoresis. The specific activities of the purified rat liver malic enzyme from the least two steps were between 28.0 and 30.5 units per mg of protein. Homogeneity of the purified enzyme was determined by disc and starch gel electrophoresis as well as sedimentation velocity and sedimentation equilibrium studies. The molecular weight and S20, w values of rat liver malic enzyme are 268,000  and 10.2, respectively. Amino acid analysis based on milligram of protein hydrolyzed yielded higher amounts of leucine and glutamic acid but lower quantities of alanine and voline per subunit than the corresponding Escherichia coli enzyme...", "contents": "Nicotinamide adenine dinucleotide phosphate-malic enzyme of rat liver. Purification, properties, and immunochemical studies. Rat liver malic enzyme (EC 1.1.1.40) was purified from livers of rats fasted and refed a high sucrose diet containing 1% desiccated thyroid powder. The purification was accomplished by a six-step procedure. The specific activity of the purified enzyme was increased 181-fold above that of the initial high speed supernatant of liver extracts. Slight additional purification of malic enzyme was achieved with preparative disc electrophoresis. The specific activities of the purified rat liver malic enzyme from the least two steps were between 28.0 and 30.5 units per mg of protein. Homogeneity of the purified enzyme was determined by disc and starch gel electrophoresis as well as sedimentation velocity and sedimentation equilibrium studies. The molecular weight and S20, w values of rat liver malic enzyme are 268,000  and 10.2, respectively. Amino acid analysis based on milligram of protein hydrolyzed yielded higher amounts of leucine and glutamic acid but lower quantities of alanine and voline per subunit than the corresponding Escherichia coli enzyme..."}
{"id": "PMID:237886", "title": "A deoxyribonucleic acid ligase from nuclei of rat liver. Purification and properties.", "content": "A DNA ligase has been extensively purified from nuclei of rat livers. The ligase seals single strand nicks in DNA with any of the four usual bases on either the 3 or 5 sides. It requires ATP and a divalent cation (Mg-2plus or Mn-2plus) for activity. At low Mg-2plus concentrations the activity is greatly stimulated by a variety of monovalent cations. Relatively small excesses of either monovalent or divalent cation above the amounts which give maximal activity lead to inhibition of activity. Poly(G) and poly(I) inhibit ligase activity; several other polyribonucleotides are not inhibitory. Low concentrations of inorganic pyrophosphate are inhibitory. The molecular weight of the ligase is estimated from gel filtration to be about 10 times 10-4.", "contents": "A deoxyribonucleic acid ligase from nuclei of rat liver. Purification and properties. A DNA ligase has been extensively purified from nuclei of rat livers. The ligase seals single strand nicks in DNA with any of the four usual bases on either the 3 or 5 sides. It requires ATP and a divalent cation (Mg-2plus or Mn-2plus) for activity. At low Mg-2plus concentrations the activity is greatly stimulated by a variety of monovalent cations. Relatively small excesses of either monovalent or divalent cation above the amounts which give maximal activity lead to inhibition of activity. Poly(G) and poly(I) inhibit ligase activity; several other polyribonucleotides are not inhibitory. Low concentrations of inorganic pyrophosphate are inhibitory. The molecular weight of the ligase is estimated from gel filtration to be about 10 times 10-4."}
{"id": "PMID:237887", "title": "Effects of 6- and 8-substituted analogs of adenosine 3':5'-monophosphate on phosphoenolpyruvate carboxykinase and tyrosine aminotransferase in hepatoma cell cultures.", "content": "A variety of 6- and 8-substituted analogs of cAMP (cyclic adenosine 3:5-monophosphate) have been tested for their ability to increase activity of tyrosine aminotransferase (EC 2.6.1.5) in cultured Reuber H35 hepatoma cells. Some analogs, particularly the 8-thio-substituted ones, produced effects approximately equivalent to those generated by N-6, O2'-dibutyryl cAMP. In contrast, cAMP and its O-2-monobutyryl derivative were relatively ineffective even at very high concentrations, whereas three other analogs actually depressed the activity of the aminotransferase. Changes in enzyme activity generated by the various analogs were paralleled closely by changes in the relative rate of aminotransferase synthesis. An excellent correlation was found to exist between the ability of any given analog to influence the activity of tyrosine aminotransferase and that of phosphoenolpyruvate carboxykinase (EC 4.1.1.32). A similar correlation was found to exist between the ability of various analogs to evelate the activity of these enzymes and to inhibit reversibly the growth of H35 cells. Only one of five inhibitors of cAMP phosphodiesterase activity tested produce any increase in aminotransferase activity when added alone. All of the 6- and 8-substituted analogs tested, including noniducers, stimulated f1 histone phosphorylation in crude rat liver extracts with approximately equal potencies. On the other hand, dibutyryl cAMP was only a weak activator of protein kinase in vitro, even though it is a potent enzyme inducer. A possible resolution of this apparent discrepancy has been provided by preliminary analyses of site-specific f1 histone phosphorylation in whole cells. Only compounds active as aminotransferase inducers are capable of stimulating phosphorylation of the serine-37 residue of endogenous f1 histone (3- to 10-fold).", "contents": "Effects of 6- and 8-substituted analogs of adenosine 3':5'-monophosphate on phosphoenolpyruvate carboxykinase and tyrosine aminotransferase in hepatoma cell cultures. A variety of 6- and 8-substituted analogs of cAMP (cyclic adenosine 3:5-monophosphate) have been tested for their ability to increase activity of tyrosine aminotransferase (EC 2.6.1.5) in cultured Reuber H35 hepatoma cells. Some analogs, particularly the 8-thio-substituted ones, produced effects approximately equivalent to those generated by N-6, O2'-dibutyryl cAMP. In contrast, cAMP and its O-2-monobutyryl derivative were relatively ineffective even at very high concentrations, whereas three other analogs actually depressed the activity of the aminotransferase. Changes in enzyme activity generated by the various analogs were paralleled closely by changes in the relative rate of aminotransferase synthesis. An excellent correlation was found to exist between the ability of any given analog to influence the activity of tyrosine aminotransferase and that of phosphoenolpyruvate carboxykinase (EC 4.1.1.32). A similar correlation was found to exist between the ability of various analogs to evelate the activity of these enzymes and to inhibit reversibly the growth of H35 cells. Only one of five inhibitors of cAMP phosphodiesterase activity tested produce any increase in aminotransferase activity when added alone. All of the 6- and 8-substituted analogs tested, including noniducers, stimulated f1 histone phosphorylation in crude rat liver extracts with approximately equal potencies. On the other hand, dibutyryl cAMP was only a weak activator of protein kinase in vitro, even though it is a potent enzyme inducer. A possible resolution of this apparent discrepancy has been provided by preliminary analyses of site-specific f1 histone phosphorylation in whole cells. Only compounds active as aminotransferase inducers are capable of stimulating phosphorylation of the serine-37 residue of endogenous f1 histone (3- to 10-fold)."}
{"id": "PMID:237888", "title": "Nuclear relaxation studies on human methemoglobin. Observation of cooperativity and alkaline Bohr effect with inositol hexaphosphate.", "content": "Ehanced spin-lattice relaxation (1/t1) of water protons induced by the heme iron of human aquomethemoglobin is exchanged-limited (koff = 1.4 times 10-4 per s at 30 degrees, H+ =7.5 Cal per mol) as indicated by the temperature and frequencey dependencies. A comparison of deuteron and proton relaxation rates revealed an order of magnitude primary isotope effect and a small inverse secondary isotope effect on the escape rate of protons from the heme iron into bulk water establishing the exchange of protons and not the exchange of the entire water molecule to be the chemical mechanism of the entire water molecule to be the chemical mechanism of the exchange process. With fluoromethemoglobin, the relaxation rate is in the fast exchange region. The results can be understood in terms of a water molecule interacting with the heme iron at an iron to proton distance less than 3.4 A in aquomethemoglobin and a single proton at a distance of 4.11 A assignable to the NH proton of the distal histidine imidazole group in fluoromethemoglobin. The relaxation rates are pH-dependent and normal titrations with Hill coefficients n = 1 are observed. The pKa is less than or equal to 6. 7 with aquomethemoglobin and 8.5 with fluoromethemoglobin at 30 degrees C. The binding of inositol hexaphosphate in stoichiometric amounts has no significant effect on the magnetic susceptibility of solutions of aquomethemoglobin and fluoromethemoglobin, but in the former case it increases koff to 3.8 times 10-4 per s by lowering the H+ barrier to 6.8 Cal per mol. In fluoromethemoglobin, inositol hexaphosphate decreases the iron to distal histidine NH distance by 0.17 A and the electron relaxation time taus by 10% as determined by the frequency dependence of 1/T1. In the aquomethemoglobin system, inositol hexaphosphate induces a Bohr effect, raising the pKa of the ionization responsible for the 1/T1 titration to 7.2, and induces cooperativity in the pH titration with a Hill coeffocoemt n = 2.8 plus or minus 0.1. With fluoromethemoglobin, the normal pH titration curve is unaffected by inositol hexaphosphate (n approximately equal to 1). Further, relaxivity titrations with varying amounts of azide and fluoride near neutral pH show normal behavior (n = 1) with and without inositol hexaphosphate. These results indicated that inositol hexaphosphate alters the quaternary structure of methemoglobin to the deoxy conformation without causing a change in the spin state of the heme iron...", "contents": "Nuclear relaxation studies on human methemoglobin. Observation of cooperativity and alkaline Bohr effect with inositol hexaphosphate. Ehanced spin-lattice relaxation (1/t1) of water protons induced by the heme iron of human aquomethemoglobin is exchanged-limited (koff = 1.4 times 10-4 per s at 30 degrees, H+ =7.5 Cal per mol) as indicated by the temperature and frequencey dependencies. A comparison of deuteron and proton relaxation rates revealed an order of magnitude primary isotope effect and a small inverse secondary isotope effect on the escape rate of protons from the heme iron into bulk water establishing the exchange of protons and not the exchange of the entire water molecule to be the chemical mechanism of the entire water molecule to be the chemical mechanism of the exchange process. With fluoromethemoglobin, the relaxation rate is in the fast exchange region. The results can be understood in terms of a water molecule interacting with the heme iron at an iron to proton distance less than 3.4 A in aquomethemoglobin and a single proton at a distance of 4.11 A assignable to the NH proton of the distal histidine imidazole group in fluoromethemoglobin. The relaxation rates are pH-dependent and normal titrations with Hill coefficients n = 1 are observed. The pKa is less than or equal to 6. 7 with aquomethemoglobin and 8.5 with fluoromethemoglobin at 30 degrees C. The binding of inositol hexaphosphate in stoichiometric amounts has no significant effect on the magnetic susceptibility of solutions of aquomethemoglobin and fluoromethemoglobin, but in the former case it increases koff to 3.8 times 10-4 per s by lowering the H+ barrier to 6.8 Cal per mol. In fluoromethemoglobin, inositol hexaphosphate decreases the iron to distal histidine NH distance by 0.17 A and the electron relaxation time taus by 10% as determined by the frequency dependence of 1/T1. In the aquomethemoglobin system, inositol hexaphosphate induces a Bohr effect, raising the pKa of the ionization responsible for the 1/T1 titration to 7.2, and induces cooperativity in the pH titration with a Hill coeffocoemt n = 2.8 plus or minus 0.1. With fluoromethemoglobin, the normal pH titration curve is unaffected by inositol hexaphosphate (n approximately equal to 1). Further, relaxivity titrations with varying amounts of azide and fluoride near neutral pH show normal behavior (n = 1) with and without inositol hexaphosphate. These results indicated that inositol hexaphosphate alters the quaternary structure of methemoglobin to the deoxy conformation without causing a change in the spin state of the heme iron..."}
{"id": "PMID:237889", "title": "Effect of protein concentration on the molecular weight of delta5-3-ketosteroid isomerase.", "content": "The molecular weight of delta-5-3-ketosteroid isomerase from Pseudomonas testosteroni was determined by means of sedimentation equilibrium and exclusion chromatography over a wide range of enzyme concentrations in 0.2 M potassium phosphate buffer, pH 7.0. In addition, the sedimentation constant of the enzyme was determinded over an extended range of concentrations. The enzyme was found to have a molecular weight of 26,000 plus or equal to 1,000, suggesting that it is a dimer of identical or similar 13,400 molecular weight polypeptide chains. In the ultracentrifuge this dimeric species was found to undergo aggregation at enzyme concentrations above 2 mg per ml and dissociation at enzyme concentrations below 0.05 mg per ml. Exclusion chromatography studies indicate that under the conditions of chromatography the oligomeric enzyme is partially dissociated at enzyme concentrations in the range 0.2 to 0.002 mug per ml. These results suggest that under conditions of enzyme assay in 0.2 M potassium phosphate buffer, pH 7.0, isomerase is in a monomeric state of aggregation.", "contents": "Effect of protein concentration on the molecular weight of delta5-3-ketosteroid isomerase. The molecular weight of delta-5-3-ketosteroid isomerase from Pseudomonas testosteroni was determined by means of sedimentation equilibrium and exclusion chromatography over a wide range of enzyme concentrations in 0.2 M potassium phosphate buffer, pH 7.0. In addition, the sedimentation constant of the enzyme was determinded over an extended range of concentrations. The enzyme was found to have a molecular weight of 26,000 plus or equal to 1,000, suggesting that it is a dimer of identical or similar 13,400 molecular weight polypeptide chains. In the ultracentrifuge this dimeric species was found to undergo aggregation at enzyme concentrations above 2 mg per ml and dissociation at enzyme concentrations below 0.05 mg per ml. Exclusion chromatography studies indicate that under the conditions of chromatography the oligomeric enzyme is partially dissociated at enzyme concentrations in the range 0.2 to 0.002 mug per ml. These results suggest that under conditions of enzyme assay in 0.2 M potassium phosphate buffer, pH 7.0, isomerase is in a monomeric state of aggregation."}
{"id": "PMID:237890", "title": "Kinetic study by pulse radiolysis of the lactate dehydrogenase-catalyzed chain oxidation of nicotinamide adenine dinucleotide by HO2 and O2-RADICALS.", "content": "The lactate dehydrogenase-catalyzed chain oxidation of NADH (LDH-NADH) by the superoxide radicals, HO2 and O2, has been studied with pulse radiolysis in the pH range between 4.5 and 9.0. The rate constants for the oxidation of the LDH-NADH by HO2 and O2 determined at 23 degrees are 1.2 times 10-6 M(-1) s(-1) and 3.6 times 10-4 M(-1) s(-1), respectively. The latter represents an activation of over 1000-fold by the enzyme. A chain reaction mechanism consistent with the results from these kinetic studies has been proposed.", "contents": "Kinetic study by pulse radiolysis of the lactate dehydrogenase-catalyzed chain oxidation of nicotinamide adenine dinucleotide by HO2 and O2-RADICALS. The lactate dehydrogenase-catalyzed chain oxidation of NADH (LDH-NADH) by the superoxide radicals, HO2 and O2, has been studied with pulse radiolysis in the pH range between 4.5 and 9.0. The rate constants for the oxidation of the LDH-NADH by HO2 and O2 determined at 23 degrees are 1.2 times 10-6 M(-1) s(-1) and 3.6 times 10-4 M(-1) s(-1), respectively. The latter represents an activation of over 1000-fold by the enzyme. A chain reaction mechanism consistent with the results from these kinetic studies has been proposed."}
{"id": "PMID:237891", "title": "Effect of N-bromosuccinimide modification on dihydrofolate reductase from a methotrexate-resistant strain of Escherichia coli. Activity, spectrophotometric, fluorescence and circular dichroism studies.", "content": "When dihydrofolate reductase from a methotrexate-resistant strain of Escherichia coli B, MB 1428, is treated with approximately a 5 mol ratio of N-bromosuccinimide (NBS) to enzyme at pH 7.2 and assayed at the same pH, there is a 40% loss of activity due to the modification of 1 histidine residue and possibly 1 methionine residue before oxidation of tryptophan occurs. The initial modification is accompanied by a shift of the pH for maximal enzymatic activity from pH 7.2 to pH 5.5 Upon further treatment with N-bromosuccinimide, the activity is gradually reduced from 60 to 0% as tryptophan residues become oxidized. An NBS to enzyme mole ratio of approximately 20 results in 90% inactivation of the enzyme. When the enzyme is titrated with NBS in 6 M guanidine HCl, 5 mol of tryptophan react per mol of enzyme, a result in agreement with the total tryptophan content as determined by magnetic circular dichroism. The 40% NBS-inactivated sample posses full binding capacity for methotrexate and reduced triphosphopyridine nucleotide, and the Km values for dihydrofolate and TPNH are the same as for the native enzyme. After 90% inactivation, only half of the enzyme molecules bind methotrexate, and the dissociation constant for methotrexate is 40 nM as compared to 4 nM for native enzyme in solutions of 0.1 M ionic strength, pH 7.2 Also, TPNH is not bound as tightly to the modified enzyme-methotrexate complex as to the unmodified enzyme-methotrexate complex. Circular dichroism studies indicate the 90% NBS-inactivated enzyme has the same alpha helix content as the native enzyme but less beta structure, while the 40% inactivated enzyme is essentially the same as the native enzyme. Protection experiments were complicated by the fact that NBS reacts with the substrates and cofactors of the enzyme. Although protection of specific residues was not determined, it was clear that TPNH was partially protected from NBS reaction when bound to the enzyme, and the enzyme, and the enzyme was not inactivated by NBS until the TPNH had reacted.", "contents": "Effect of N-bromosuccinimide modification on dihydrofolate reductase from a methotrexate-resistant strain of Escherichia coli. Activity, spectrophotometric, fluorescence and circular dichroism studies. When dihydrofolate reductase from a methotrexate-resistant strain of Escherichia coli B, MB 1428, is treated with approximately a 5 mol ratio of N-bromosuccinimide (NBS) to enzyme at pH 7.2 and assayed at the same pH, there is a 40% loss of activity due to the modification of 1 histidine residue and possibly 1 methionine residue before oxidation of tryptophan occurs. The initial modification is accompanied by a shift of the pH for maximal enzymatic activity from pH 7.2 to pH 5.5 Upon further treatment with N-bromosuccinimide, the activity is gradually reduced from 60 to 0% as tryptophan residues become oxidized. An NBS to enzyme mole ratio of approximately 20 results in 90% inactivation of the enzyme. When the enzyme is titrated with NBS in 6 M guanidine HCl, 5 mol of tryptophan react per mol of enzyme, a result in agreement with the total tryptophan content as determined by magnetic circular dichroism. The 40% NBS-inactivated sample posses full binding capacity for methotrexate and reduced triphosphopyridine nucleotide, and the Km values for dihydrofolate and TPNH are the same as for the native enzyme. After 90% inactivation, only half of the enzyme molecules bind methotrexate, and the dissociation constant for methotrexate is 40 nM as compared to 4 nM for native enzyme in solutions of 0.1 M ionic strength, pH 7.2 Also, TPNH is not bound as tightly to the modified enzyme-methotrexate complex as to the unmodified enzyme-methotrexate complex. Circular dichroism studies indicate the 90% NBS-inactivated enzyme has the same alpha helix content as the native enzyme but less beta structure, while the 40% inactivated enzyme is essentially the same as the native enzyme. Protection experiments were complicated by the fact that NBS reacts with the substrates and cofactors of the enzyme. Although protection of specific residues was not determined, it was clear that TPNH was partially protected from NBS reaction when bound to the enzyme, and the enzyme, and the enzyme was not inactivated by NBS until the TPNH had reacted."}
{"id": "PMID:237892", "title": "Coordinated incorporation of nascent peptidoglycan and teichoic acid into pneumococcal cell walls and conservation of peptidoglycan during growth.", "content": "Choline-containing pneumococcal cell wals are sensitive to autolysin, whereas ethanolamine-containing walls are not. Bacteria were labeled with radioactive peptidoglycan precursors while growing either in choline- or in ethanolaminecontaining media. Subsequently, the labeled cells were allowed to grow for four to five generations in nonradioactive medium supplemented with the alternative amino alcohol source (i.e. cells labeled in choline medium yields ethanolamine; cells labeled in ethanolamine medium yields choline). The autolysin sensitivity of the isotope label in cell walls prepared from such bacteria indicates that nascent peptidoglycan and teichoic acid units that are synthesized at the same time are attached to one another, incorporated into the cell surface at the cellular equator, and remain conserved during growth the division of the bacteria.", "contents": "Coordinated incorporation of nascent peptidoglycan and teichoic acid into pneumococcal cell walls and conservation of peptidoglycan during growth. Choline-containing pneumococcal cell wals are sensitive to autolysin, whereas ethanolamine-containing walls are not. Bacteria were labeled with radioactive peptidoglycan precursors while growing either in choline- or in ethanolaminecontaining media. Subsequently, the labeled cells were allowed to grow for four to five generations in nonradioactive medium supplemented with the alternative amino alcohol source (i.e. cells labeled in choline medium yields ethanolamine; cells labeled in ethanolamine medium yields choline). The autolysin sensitivity of the isotope label in cell walls prepared from such bacteria indicates that nascent peptidoglycan and teichoic acid units that are synthesized at the same time are attached to one another, incorporated into the cell surface at the cellular equator, and remain conserved during growth the division of the bacteria."}
{"id": "PMID:237893", "title": "Altered ganglioside biosynthesis in mouse cell cultures following transformation with chemical carcinogens and x-irradiation.", "content": "Chemicaly and x-ray-transformed subclones of BALB/c 3T3 mouse embryo cells were found to have reduced amounts of the mono- and disialogangliosides galactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosylceramide (Gm1) and N-acetylneuraminylgalactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosylceramide (Gd1a), and increased amounts of N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosylceramide (Gm2). The activity of the enzyme UDP-Gal:Gm2 galactosyltransferase was reduced to between 2.7 and 14.3% of normal in the transformed clones. Other ganglioside glycosyltransferase activities were unaffected. This enzymatic change was consistent with the observed alteration in ganglioside pattern in the transformed cells. The residual galactosyltransferase activity in the transformed cells was kinetically similar to the normal enzyme, suggesting that transformation alters ganglioside biosynthesis by blocking enzyme synthesis at the translational or transcriptional levels.", "contents": "Altered ganglioside biosynthesis in mouse cell cultures following transformation with chemical carcinogens and x-irradiation. Chemicaly and x-ray-transformed subclones of BALB/c 3T3 mouse embryo cells were found to have reduced amounts of the mono- and disialogangliosides galactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosylceramide (Gm1) and N-acetylneuraminylgalactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosylceramide (Gd1a), and increased amounts of N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosylceramide (Gm2). The activity of the enzyme UDP-Gal:Gm2 galactosyltransferase was reduced to between 2.7 and 14.3% of normal in the transformed clones. Other ganglioside glycosyltransferase activities were unaffected. This enzymatic change was consistent with the observed alteration in ganglioside pattern in the transformed cells. The residual galactosyltransferase activity in the transformed cells was kinetically similar to the normal enzyme, suggesting that transformation alters ganglioside biosynthesis by blocking enzyme synthesis at the translational or transcriptional levels."}
{"id": "PMID:237894", "title": "A novel diazonium-sulfhydryl reaction in the inactivation of yeast alcohol dehydrogenase by diazotized 3-aminopyridine adenine dinucleotide.", "content": "Diazotized 3-aminopyridine adenine dinucleotide has been found to modify four sulfhydryl groups per molecule of enzyme during the complete inactivation of yeast alcohol dehydrogenase. The reaction of sulfhydryl groups was indicated by titration studies with 5,5-dithiobis(2-nitrobenzoic acid) as well as isolation and quantitation of the cysteinyl derivative released by acid hydrolysis of the modified enzyme. The cysteinyl derivative was identified as S-(3-pyridyl)cysteine. Authentic S-(3-pyridyl)cystein was synthesized and structurally characterized for these studies. Diazonium-sulfhydryl reactions were demonstrated for a number of diazonium derivatives with cysteine, homocysteine, glutathione, and mercaptoethanol at 0-4 degrees and neutral pH. Second order rate constants were determined in reactions of these sulfhydryl compounds with diazotized 1-methyl-3-aminopyridinium chloride, diazotized 3-aminopyridine adenine dinucleotide, and diazotized 3-aminopyridine adenine dinucleotide phosphate.", "contents": "A novel diazonium-sulfhydryl reaction in the inactivation of yeast alcohol dehydrogenase by diazotized 3-aminopyridine adenine dinucleotide. Diazotized 3-aminopyridine adenine dinucleotide has been found to modify four sulfhydryl groups per molecule of enzyme during the complete inactivation of yeast alcohol dehydrogenase. The reaction of sulfhydryl groups was indicated by titration studies with 5,5-dithiobis(2-nitrobenzoic acid) as well as isolation and quantitation of the cysteinyl derivative released by acid hydrolysis of the modified enzyme. The cysteinyl derivative was identified as S-(3-pyridyl)cysteine. Authentic S-(3-pyridyl)cystein was synthesized and structurally characterized for these studies. Diazonium-sulfhydryl reactions were demonstrated for a number of diazonium derivatives with cysteine, homocysteine, glutathione, and mercaptoethanol at 0-4 degrees and neutral pH. Second order rate constants were determined in reactions of these sulfhydryl compounds with diazotized 1-methyl-3-aminopyridinium chloride, diazotized 3-aminopyridine adenine dinucleotide, and diazotized 3-aminopyridine adenine dinucleotide phosphate."}
{"id": "PMID:237895", "title": "Purification and properties of hyaluronidase from bull sperm.", "content": "Hyaluronidase from bull sperm was fractionated by ammonium sulfate and further purified by DEAE-cellulose and Sephadex chromatography. The highly purified hyaluronidase preparation showed 2,370 units per mg of protein (68,730 N.F. units per mg of protein), i.e. 182-fold purification. Disc gel electrophoresis showed one major component. The molecular weight of bull sperm hyaluronidase was 62,000 by sodium dodecyl sulfate gel electrophoresis. Hyaluronidase from bull sperm has optimum activity at pH 3.8 and an absolute requirement for cations. Kplus and Naplus have a greater effect than Ca2plus, Mg2plus, and Mn2plus, whereas Co2plus, Cu2plus, and Zn2plus do not affect the enzyme activity. Purified preparations are less stable than crude extracts stored frozen at minus 15 degrees. Km of hyaluronidase with hyaluronic acid as substrate is 3.7 mg per ml and Vmax is 2.4 mumol per min by Hofstee plot.", "contents": "Purification and properties of hyaluronidase from bull sperm. Hyaluronidase from bull sperm was fractionated by ammonium sulfate and further purified by DEAE-cellulose and Sephadex chromatography. The highly purified hyaluronidase preparation showed 2,370 units per mg of protein (68,730 N.F. units per mg of protein), i.e. 182-fold purification. Disc gel electrophoresis showed one major component. The molecular weight of bull sperm hyaluronidase was 62,000 by sodium dodecyl sulfate gel electrophoresis. Hyaluronidase from bull sperm has optimum activity at pH 3.8 and an absolute requirement for cations. Kplus and Naplus have a greater effect than Ca2plus, Mg2plus, and Mn2plus, whereas Co2plus, Cu2plus, and Zn2plus do not affect the enzyme activity. Purified preparations are less stable than crude extracts stored frozen at minus 15 degrees. Km of hyaluronidase with hyaluronic acid as substrate is 3.7 mg per ml and Vmax is 2.4 mumol per min by Hofstee plot."}
{"id": "PMID:237896", "title": "Postillumination adenosine triphosphate synthesis in Rhodospirillum rubrum chromatophores. I. Conditions for maximal yields.", "content": "The very low level of postillumination ATP synthesis in chromatophores was markedly stimulated when permeant anions (thiocyanate or perchlorate) or permeant cations (potassium in the presence of valinomycin) were added to the light stage. Although these compounds stimulated also light-induced proton uptake in chromatophores the pH dependence of both photoreactions was different. Proton uptake peaked at pH 6.5 while the amount of postillumination ATP was maximal when the light stage was carried out around pH 7.7. The increased yield of ATP at the more alkaline pH could not be explained by a slower decay of the high energy state at this pH, since the decay rate was faster at pH 7.7 than at pH 6.5. The proton concentration gradient which is maintained across the chromatophore membrane in the light was also found to increase when the external pH was raised from 6.0 to 8.0. Only a minimal amount of postillumination ATP was formed when this gradient was below 2.1 pH units, but above this value the ATP yield rose steeply as a function of the increasing pH gradient. In light of these results it is suggested that in order to obtain a high yield of postillumination ATP synthesis in chromatophores two conditions are required: the particles have to be loaded with a sufficient number of protons and a light-induced pH gradient above a certain threshold value has to be maintained across their membrane. The low yield of postillumination ATP in chromatophores and the increase obtained by adding permeating ions, is thus explained by similar variations in the extent of the pH gradient, which exceeded the threshold value only in the presence of the permeating ions.", "contents": "Postillumination adenosine triphosphate synthesis in Rhodospirillum rubrum chromatophores. I. Conditions for maximal yields. The very low level of postillumination ATP synthesis in chromatophores was markedly stimulated when permeant anions (thiocyanate or perchlorate) or permeant cations (potassium in the presence of valinomycin) were added to the light stage. Although these compounds stimulated also light-induced proton uptake in chromatophores the pH dependence of both photoreactions was different. Proton uptake peaked at pH 6.5 while the amount of postillumination ATP was maximal when the light stage was carried out around pH 7.7. The increased yield of ATP at the more alkaline pH could not be explained by a slower decay of the high energy state at this pH, since the decay rate was faster at pH 7.7 than at pH 6.5. The proton concentration gradient which is maintained across the chromatophore membrane in the light was also found to increase when the external pH was raised from 6.0 to 8.0. Only a minimal amount of postillumination ATP was formed when this gradient was below 2.1 pH units, but above this value the ATP yield rose steeply as a function of the increasing pH gradient. In light of these results it is suggested that in order to obtain a high yield of postillumination ATP synthesis in chromatophores two conditions are required: the particles have to be loaded with a sufficient number of protons and a light-induced pH gradient above a certain threshold value has to be maintained across their membrane. The low yield of postillumination ATP in chromatophores and the increase obtained by adding permeating ions, is thus explained by similar variations in the extent of the pH gradient, which exceeded the threshold value only in the presence of the permeating ions."}
{"id": "PMID:237897", "title": "Bakers' yeast uridine nucleosidase. Purification, composition, and physical and enzymatic properties.", "content": "Uridine nucleosidase (EC 3.2.2.3) was purified from commercial bakers' yeast to homogeneity, as judged by a single band observed on polyacrylamide disc gel electrophoresis. The molecular weight of the enzyme, estimated by gel filtration, was approximately 32,500. Polyacrylamide electrophoresis in 0.2% sodium dodecyl sulfate showed the presence of two apparently identical subunits of 17,000 molecular weight. The amino acid composition indicated a large excess of glutamic acid and aspartic acid over other amino acid residues and a very low content of tyrosine and tryptophan. Th SH groups analysis performed with 5,5'-dithiobis (2-nitrobenzoic acid) on thenative protein as well as in the presence of 1% sodium dodecyl  sulfate showed the existence of one sulfhydryl group per mole of enzyme. Uridine nucleosidase is active on uridine and 5-methyluridine (ribosylthymine) resulting inactive toward all other pyrimidine and purine nucleosides tested. The Km values for uridine and 5-methyluridine were 0.86 x 10(-3) M and 1.66x10--3M, respectively. The optimal pH is around 7.0. The isoelectric point is 5.1. Among a variety of compounds tested only ribose and glucose 6-phosphate were inhibitory and Ki values were 7.2 mM and 0.19 mM, respectively. Furthermore, ribosylthymine competitively inhibited the hydrolysis of uridine. The type of all inhibitions was competitive and the n' values of the Hill plots were near 1. The effect of temperature on the enzyme activity plotted accoring to Arrhenius gave a value of E = 4740 cal per mole. The enzyme in 100 mM phosphate, pH = 7.0, is stable at 4 degrees for 15 days without any loss of activity.", "contents": "Bakers' yeast uridine nucleosidase. Purification, composition, and physical and enzymatic properties. Uridine nucleosidase (EC 3.2.2.3) was purified from commercial bakers' yeast to homogeneity, as judged by a single band observed on polyacrylamide disc gel electrophoresis. The molecular weight of the enzyme, estimated by gel filtration, was approximately 32,500. Polyacrylamide electrophoresis in 0.2% sodium dodecyl sulfate showed the presence of two apparently identical subunits of 17,000 molecular weight. The amino acid composition indicated a large excess of glutamic acid and aspartic acid over other amino acid residues and a very low content of tyrosine and tryptophan. Th SH groups analysis performed with 5,5'-dithiobis (2-nitrobenzoic acid) on thenative protein as well as in the presence of 1% sodium dodecyl  sulfate showed the existence of one sulfhydryl group per mole of enzyme. Uridine nucleosidase is active on uridine and 5-methyluridine (ribosylthymine) resulting inactive toward all other pyrimidine and purine nucleosides tested. The Km values for uridine and 5-methyluridine were 0.86 x 10(-3) M and 1.66x10--3M, respectively. The optimal pH is around 7.0. The isoelectric point is 5.1. Among a variety of compounds tested only ribose and glucose 6-phosphate were inhibitory and Ki values were 7.2 mM and 0.19 mM, respectively. Furthermore, ribosylthymine competitively inhibited the hydrolysis of uridine. The type of all inhibitions was competitive and the n' values of the Hill plots were near 1. The effect of temperature on the enzyme activity plotted accoring to Arrhenius gave a value of E = 4740 cal per mole. The enzyme in 100 mM phosphate, pH = 7.0, is stable at 4 degrees for 15 days without any loss of activity."}
{"id": "PMID:237898", "title": "Determination of the pK values for the alpha-amino groups of human hemoglobin.", "content": "The rate of reaction between alpha-amino groups and cyanic acid was followed at 26 degrees and ionic strength 0.2 M as a function of pH of human hemoglobin Ao solutions to determine the pK and the pH-independent second order rate constant, kappa, for these groups in the alpha and beta chains. At a given point in time, the extent of the reaction was determined by employing the Beckmann Sequencer as a quantitative tool in which the yields of leucine and histidine in the second Edman degradation cycle were used to define the rates of reaction of the alpha and beta chains, respectively. From these results, the individual were evaluated (Garner, M.H., Garner, W.H., and Gurd, F. R.N. (1973) J. Biol. Chem. 248, 5451-5455). Values for pK for the alpha and beta chains were, respectively, 6.74 and 6.93 for cyanoferrihemoglobin, 6.95 and 7.05 for carboxyhemoglobin, and 7.79 and 6.84 for deoxyhemoglobin. Values for kappa, M- minus 1 S-minus 1, for the alpha and beta chains were, respectively, 12.5 and 17 for cyanoferrihemoglobin, 12 and 18 for carboxyhemoglobin, and 91 and 24 for deoxyhemoglobin. Limits of significance were estimated for both variables in each case. The pK results for valine 1alpha agree well with the value obtained by Hill and Davis (1967) J. Biol. Chem. 242, 2005-2012) for carboxyhemoglobin and with that of Kilmartin and Rossi-Bernardi ((1971) Biochem. J. 124, 31-45) for deoxyhemoglobin. Values obtained for sperm whale myoglobin were 7.77 for pK and 7.4 for kappa. The results are useful for the interpretation of the allosteric interactions of hemoglobin with hydrogen ions, with CO2, and with phosphate.", "contents": "Determination of the pK values for the alpha-amino groups of human hemoglobin. The rate of reaction between alpha-amino groups and cyanic acid was followed at 26 degrees and ionic strength 0.2 M as a function of pH of human hemoglobin Ao solutions to determine the pK and the pH-independent second order rate constant, kappa, for these groups in the alpha and beta chains. At a given point in time, the extent of the reaction was determined by employing the Beckmann Sequencer as a quantitative tool in which the yields of leucine and histidine in the second Edman degradation cycle were used to define the rates of reaction of the alpha and beta chains, respectively. From these results, the individual were evaluated (Garner, M.H., Garner, W.H., and Gurd, F. R.N. (1973) J. Biol. Chem. 248, 5451-5455). Values for pK for the alpha and beta chains were, respectively, 6.74 and 6.93 for cyanoferrihemoglobin, 6.95 and 7.05 for carboxyhemoglobin, and 7.79 and 6.84 for deoxyhemoglobin. Values for kappa, M- minus 1 S-minus 1, for the alpha and beta chains were, respectively, 12.5 and 17 for cyanoferrihemoglobin, 12 and 18 for carboxyhemoglobin, and 91 and 24 for deoxyhemoglobin. Limits of significance were estimated for both variables in each case. The pK results for valine 1alpha agree well with the value obtained by Hill and Davis (1967) J. Biol. Chem. 242, 2005-2012) for carboxyhemoglobin and with that of Kilmartin and Rossi-Bernardi ((1971) Biochem. J. 124, 31-45) for deoxyhemoglobin. Values obtained for sperm whale myoglobin were 7.77 for pK and 7.4 for kappa. The results are useful for the interpretation of the allosteric interactions of hemoglobin with hydrogen ions, with CO2, and with phosphate."}
{"id": "PMID:237899", "title": "Three photo-cross-linked complexes of yeast phenylalanine specific transfer ribonucleic acid with aminoacyl transfer ribonucleic acid synthetases.", "content": "Yeast tRNA-Phe has been cross-linked photochemically to three aminoacyl-tRNA synthetases, yeast phenylalanyl-tRNA synthetase, Escherichia coli isoleucyl-tRNA synthetase, and E. coli valyl-tRNA synthetase. The two non-cognate enzymes are known to interact with tRNA-Phe. In each complex, three regions on the tRNA are found to cross-link. Two of these are common to all of the complexes, while the third is unique to each. Thus, the cognate and non-cognate complexes bear considerable similarity to each other in the way in which the respective enzyme orients on tRNA-Phe, a result which was also established for the complexes of E. coli tRNA-Ile (BUDZIK, G.P., LAM, S.M., SCHOEMAKER, H.J.P., and SCHIMMEL, P.R. (1975) J. Biol. Chem. 250, 4433-4439). The common regions include a piece extending from the 5'-side of the acceptor stem to the beginning of the dihydrouridine helix, and a segment running from the 3' side of the extra loop into the TpsiC helix. These two regions overlap with and include some of the homologous bases found in eight tRNAs aminoacylated by yeast phenylalanyl-tRNA synthetase (ROE, B., SIROVER, M., and DUDOCK, B. (1973) Biochemistry 12, 4146-4153). Although well separated in the primary and secondary structure, these two segments are in close proximity in the crystallographic tertiary structure. In two of the complexes, the third cross-linked fragment is near to the two common ones. The picture which emerges is that the enzymes all interact with the general area in which the two helical branches of the L-shaped tertiary structure fuse together, with additional interactions on other parts of the tRNAas well.", "contents": "Three photo-cross-linked complexes of yeast phenylalanine specific transfer ribonucleic acid with aminoacyl transfer ribonucleic acid synthetases. Yeast tRNA-Phe has been cross-linked photochemically to three aminoacyl-tRNA synthetases, yeast phenylalanyl-tRNA synthetase, Escherichia coli isoleucyl-tRNA synthetase, and E. coli valyl-tRNA synthetase. The two non-cognate enzymes are known to interact with tRNA-Phe. In each complex, three regions on the tRNA are found to cross-link. Two of these are common to all of the complexes, while the third is unique to each. Thus, the cognate and non-cognate complexes bear considerable similarity to each other in the way in which the respective enzyme orients on tRNA-Phe, a result which was also established for the complexes of E. coli tRNA-Ile (BUDZIK, G.P., LAM, S.M., SCHOEMAKER, H.J.P., and SCHIMMEL, P.R. (1975) J. Biol. Chem. 250, 4433-4439). The common regions include a piece extending from the 5'-side of the acceptor stem to the beginning of the dihydrouridine helix, and a segment running from the 3' side of the extra loop into the TpsiC helix. These two regions overlap with and include some of the homologous bases found in eight tRNAs aminoacylated by yeast phenylalanyl-tRNA synthetase (ROE, B., SIROVER, M., and DUDOCK, B. (1973) Biochemistry 12, 4146-4153). Although well separated in the primary and secondary structure, these two segments are in close proximity in the crystallographic tertiary structure. In two of the complexes, the third cross-linked fragment is near to the two common ones. The picture which emerges is that the enzymes all interact with the general area in which the two helical branches of the L-shaped tertiary structure fuse together, with additional interactions on other parts of the tRNAas well."}
{"id": "PMID:237900", "title": "Equilibrium constants of the reactions of choline acetyltransferase, carnitine acetyltransferase, and acetylcholinesterase under physiological conditions.", "content": "The observed equilibrium constant (Kobs) for the reaction of choline acetyltransferase (EC 2.3.1.6) has been determined under physiological conditions. Using sigma and square brackets to indicate total concentrations of all ionic species present: (see article). The value of Kobs has been determined to be 12.3 plus or minus 0.6 at 38 degrees, pH 7.0 and ionic strength 0.25 M. The value at 25 degrees is not significantly different, and the constant has been found to be insensitive to variations in ionic strength (0.03 to 0.375 M), pH (6.5 TO 7.5) OR FREE [Mg-2+] (0 to 5 mM). The Kobs of this reaction reflects the difference between the observed standard free energy change (delta G-oobs) for the hydrolysis of acetylcholine and the delta G-oobs for the hydrolysis of acetyl-CoA. Since the delta G-oobs for the hydrolysis of acetyl-CoA has been previously determined to be minus 8.54 kcal/mol (minus 35.75 kJ/mol under the same physiological conditions, the delta G-oobs for the reaction of acetylcholinesterase (EC 3.1.1.7): (SEE ARTICLE). Can be calculated to be minus 6.99 kcal/mol (minus 29.26 kJ/mol) at pH ionic strength 0.25 M and 38 degrees, taking the standard state of liquid water to have unit activity ([H2O] equals 1). The pKa for acetic acid under the same conditions, has been determined to be 4.60 plus or minus 0.01, allowing the Kobs for the pH-independent reaction (see article). To be calculated to be 3.28 times 10-2 M. Choline and carnitine are chemical analogues. The Kobs for the corresponding reaction of carnitine acetyltransferase (EC 2.3.1.7). (SEE ARTICLE). Under the same physiological conditions of pH (7.0), ionic strength (0.25 M), and temperature (38 degrees) has been determined to be 1.73 plus or minus 0.05, making the delta G-oobs for the hydrolysis of acetylcholine only 1.21 kcal/mol (5.06 kJ) less negative than that for the hydrolysis of acetylcarnitine.", "contents": "Equilibrium constants of the reactions of choline acetyltransferase, carnitine acetyltransferase, and acetylcholinesterase under physiological conditions. The observed equilibrium constant (Kobs) for the reaction of choline acetyltransferase (EC 2.3.1.6) has been determined under physiological conditions. Using sigma and square brackets to indicate total concentrations of all ionic species present: (see article). The value of Kobs has been determined to be 12.3 plus or minus 0.6 at 38 degrees, pH 7.0 and ionic strength 0.25 M. The value at 25 degrees is not significantly different, and the constant has been found to be insensitive to variations in ionic strength (0.03 to 0.375 M), pH (6.5 TO 7.5) OR FREE [Mg-2+] (0 to 5 mM). The Kobs of this reaction reflects the difference between the observed standard free energy change (delta G-oobs) for the hydrolysis of acetylcholine and the delta G-oobs for the hydrolysis of acetyl-CoA. Since the delta G-oobs for the hydrolysis of acetyl-CoA has been previously determined to be minus 8.54 kcal/mol (minus 35.75 kJ/mol under the same physiological conditions, the delta G-oobs for the reaction of acetylcholinesterase (EC 3.1.1.7): (SEE ARTICLE). Can be calculated to be minus 6.99 kcal/mol (minus 29.26 kJ/mol) at pH ionic strength 0.25 M and 38 degrees, taking the standard state of liquid water to have unit activity ([H2O] equals 1). The pKa for acetic acid under the same conditions, has been determined to be 4.60 plus or minus 0.01, allowing the Kobs for the pH-independent reaction (see article). To be calculated to be 3.28 times 10-2 M. Choline and carnitine are chemical analogues. The Kobs for the corresponding reaction of carnitine acetyltransferase (EC 2.3.1.7). (SEE ARTICLE). Under the same physiological conditions of pH (7.0), ionic strength (0.25 M), and temperature (38 degrees) has been determined to be 1.73 plus or minus 0.05, making the delta G-oobs for the hydrolysis of acetylcholine only 1.21 kcal/mol (5.06 kJ) less negative than that for the hydrolysis of acetylcarnitine."}
{"id": "PMID:237901", "title": "Purification of terminal riboadenylate transferase from calf thymus gland.", "content": "A poly(A) polymerase has been purified from the soluble protein fraction of calf thymus gland. The activity is cytoplasmic and nonparticulate. Mn-2+ATP is the preferred substrate. On the basis of disc gel electrophoresis in sodium dodecyl sulfate-acrylamide gels, gel filtration, and sedimentation velocity in sucrose gradients, the enzyme has a molecular weight of 62,000 and appears to consist of one polypeptide chain. The enzyme preparation is shown to be nearly homogeneous by disc gel electrophoresis and isoelectric-focusing. The activity has a pI of about 7.4. The specific activity of the enzyme is about 1700 mumol per hour per mg of protein, giving a turnover number of about 1800 mol of substrate per mol of enzyme min- minus 1. The activity is highly specific for ATP and is inhibited by other ribonucleoside triphosphates. It is sensitive to high levels of RNA-polymerase inhibitors. Km for oligoadenylate is 50 muM in the presence of Mn-2+ and 200 muM in Mg-2+ and equivalent Vmax is achieved with either metal ion. The initiator function may be filled by a variety of oligoribonucleotides having a free 3'-OH.", "contents": "Purification of terminal riboadenylate transferase from calf thymus gland. A poly(A) polymerase has been purified from the soluble protein fraction of calf thymus gland. The activity is cytoplasmic and nonparticulate. Mn-2+ATP is the preferred substrate. On the basis of disc gel electrophoresis in sodium dodecyl sulfate-acrylamide gels, gel filtration, and sedimentation velocity in sucrose gradients, the enzyme has a molecular weight of 62,000 and appears to consist of one polypeptide chain. The enzyme preparation is shown to be nearly homogeneous by disc gel electrophoresis and isoelectric-focusing. The activity has a pI of about 7.4. The specific activity of the enzyme is about 1700 mumol per hour per mg of protein, giving a turnover number of about 1800 mol of substrate per mol of enzyme min- minus 1. The activity is highly specific for ATP and is inhibited by other ribonucleoside triphosphates. It is sensitive to high levels of RNA-polymerase inhibitors. Km for oligoadenylate is 50 muM in the presence of Mn-2+ and 200 muM in Mg-2+ and equivalent Vmax is achieved with either metal ion. The initiator function may be filled by a variety of oligoribonucleotides having a free 3'-OH."}
{"id": "PMID:237902", "title": "Cholesterol esterase in rat adipose tissue and its activation by cyclic adenosine 3':5'-monophosphate-dependent protein kinase.", "content": "A high level of cholesterol esterase activity, comparable to that of hormone-sensitive triglyceridase, has been demonstrated in rad adipose tissue. Essentially all of the activity was in the isolated adipocytes, primarily in the 100,000 times g supernatant fraction of the adipocytes. Cholesterol esterase activity in the 100,000 times g supernatant fraction was increased 40 plus or minus 16% by incubation with ATP (0.5 mM), Mg-2+ (1.25 mM), and cyclic adenosine 3':5'-monophosphate (cyclic AMP) (10 muM), conditions which also activated hormone-sensitive triglyceridase. Protein kinase inhibitor (rabbit skeletal muscle) blocked activation, and activation was restored by the addition of excess protein kinase (bovine skeletal muscle). In extracts prepared from adipocytes first incubated for 5 min with 10 muM epinephrine and 1 mM theophylline, there was no cyclic AMP-dependent cholesterol esterase activation, implying that the enzyme had been activated by a similar mechanism in the intact cell. The physiological role of this high level of cholesterol esterase activity in adipose tissue is unclear. Its relationship to hormone-sensitive triglyceride lipase, with which it extensively co-fractionates, and its possible involvement in fat mobilization remain to be determined.", "contents": "Cholesterol esterase in rat adipose tissue and its activation by cyclic adenosine 3':5'-monophosphate-dependent protein kinase. A high level of cholesterol esterase activity, comparable to that of hormone-sensitive triglyceridase, has been demonstrated in rad adipose tissue. Essentially all of the activity was in the isolated adipocytes, primarily in the 100,000 times g supernatant fraction of the adipocytes. Cholesterol esterase activity in the 100,000 times g supernatant fraction was increased 40 plus or minus 16% by incubation with ATP (0.5 mM), Mg-2+ (1.25 mM), and cyclic adenosine 3':5'-monophosphate (cyclic AMP) (10 muM), conditions which also activated hormone-sensitive triglyceridase. Protein kinase inhibitor (rabbit skeletal muscle) blocked activation, and activation was restored by the addition of excess protein kinase (bovine skeletal muscle). In extracts prepared from adipocytes first incubated for 5 min with 10 muM epinephrine and 1 mM theophylline, there was no cyclic AMP-dependent cholesterol esterase activation, implying that the enzyme had been activated by a similar mechanism in the intact cell. The physiological role of this high level of cholesterol esterase activity in adipose tissue is unclear. Its relationship to hormone-sensitive triglyceride lipase, with which it extensively co-fractionates, and its possible involvement in fat mobilization remain to be determined."}
{"id": "PMID:237903", "title": "Subunits of fatty acid synthetase complexes. Enzymatic activities and properties of the half-molecular weight nonidentical subunits of pigeon liver fatty acid synthetase.", "content": "The separation of the half-molecular weight, nonidentical subunits (I and II) of the pigeon liver fatty acid synthetase complex has been achieved on a large (20 mg) scale by affinity chromatography on Sepharose epsilon-aminocaproyl pantetheine. This separation requires a careful control of temperature, ionic strength, pH, and column flow rate for success. The yield of subunit II is further improved by transacetylation (with acetyl-CoA) of the dissociated fatty acid synthetase prior to affinity chromatography. The separated subunit I (reductase) contains the 4'-phosphopantetheine (A2) acyl binding site, two NADPH binding sites, and beta-ketoacyl and crotonyl thioester reductases. Subunit II (transacylase) contains the B1 (hydroxyl or loading) and B2 (cysteine) acyl binding sites, and acetyl- and malonyl-CoA: pantetheine transacylases. When subunit I is mixed in equimolar quantities with subunit II, an additional NADPH binding site is found even though subunit II alone shows no NADPH binding. Both subunits contain activities for the partial reactions, beta-hydroxybutyryl thioester dehydrase (crotonase) and palmityl-CoA deacylase. Subunit I has 8 sulfhydryl groups per mol whereas subunit II has 60. Reconstitution of fatty acid synthetase activity to 75% of the control level is achieved on reassociation of subunits I and II.", "contents": "Subunits of fatty acid synthetase complexes. Enzymatic activities and properties of the half-molecular weight nonidentical subunits of pigeon liver fatty acid synthetase. The separation of the half-molecular weight, nonidentical subunits (I and II) of the pigeon liver fatty acid synthetase complex has been achieved on a large (20 mg) scale by affinity chromatography on Sepharose epsilon-aminocaproyl pantetheine. This separation requires a careful control of temperature, ionic strength, pH, and column flow rate for success. The yield of subunit II is further improved by transacetylation (with acetyl-CoA) of the dissociated fatty acid synthetase prior to affinity chromatography. The separated subunit I (reductase) contains the 4'-phosphopantetheine (A2) acyl binding site, two NADPH binding sites, and beta-ketoacyl and crotonyl thioester reductases. Subunit II (transacylase) contains the B1 (hydroxyl or loading) and B2 (cysteine) acyl binding sites, and acetyl- and malonyl-CoA: pantetheine transacylases. When subunit I is mixed in equimolar quantities with subunit II, an additional NADPH binding site is found even though subunit II alone shows no NADPH binding. Both subunits contain activities for the partial reactions, beta-hydroxybutyryl thioester dehydrase (crotonase) and palmityl-CoA deacylase. Subunit I has 8 sulfhydryl groups per mol whereas subunit II has 60. Reconstitution of fatty acid synthetase activity to 75% of the control level is achieved on reassociation of subunits I and II."}
{"id": "PMID:237904", "title": "Crystallization and properties of L-arginine deiminase of Pseudomonas putida.", "content": "Crystalline L-arginine deiminase of Pseudomonas putida was prepared by the following steps: sonic disruption, ammonium sulfate fractionation, protamine sulfate treatment, DEAE-cellulose column chromatography, and L-arginine-Sepharose 6B chromatography followed by crystallization. This procedure yields a crystalline pure enzyme with a 45% recovery of the activity in crude cell-free extracts. The yield is significantly higher than that reported for this enzyme. The purified enzyme appears to be homogeneous in ultracentrifugation (s-o20, w equals 10.2 S) and isoelectric focusing (pI equals 6.13). The purified enzyme showed two bands on disc gel electrophoresis, both carrying out the deimination of L-arginine. Electrophoresis in the presence of beta-mercaptoethanol plus Na dodecyl-SO4 gave a single band (Mr, 54,000). Specific activity of this enzyme was 58.8 mumol of L-citrulline formed per min per mg of protein at 37 degrees. The optimum pH of the purified enzyme was 6.0 and maximal activity was obtained at 50 degrees. The molecular weight of the native protein was 130,000 by gel filtration and 120,000 by sedimentation-equilibrium measurements. The spectrum of the pure enzyme showed absorption maximum at 280 nm and the value of E-1%-1 CM AT 280 NM WAS 10.48 IN 0.05 M potassium phosphate buffer (pH 7.0). The crystalline enzyme hydrolyzed several L-arginine analogues. L-Homoarginine, L-alpha-amino-gamma-guanidinobutyric acid, and L-alpha-amino-beta-guanidinopropionic acid competitively inhibited the hydrolysis of L-arginine with Ki values of 25.7, 7.5, and 4.0 times 10- minus 3 M, respectively. p-Chloromercuribenzoate, Ag-+, and Hg-2+, and several metal ions inhibited the enzyme.", "contents": "Crystallization and properties of L-arginine deiminase of Pseudomonas putida. Crystalline L-arginine deiminase of Pseudomonas putida was prepared by the following steps: sonic disruption, ammonium sulfate fractionation, protamine sulfate treatment, DEAE-cellulose column chromatography, and L-arginine-Sepharose 6B chromatography followed by crystallization. This procedure yields a crystalline pure enzyme with a 45% recovery of the activity in crude cell-free extracts. The yield is significantly higher than that reported for this enzyme. The purified enzyme appears to be homogeneous in ultracentrifugation (s-o20, w equals 10.2 S) and isoelectric focusing (pI equals 6.13). The purified enzyme showed two bands on disc gel electrophoresis, both carrying out the deimination of L-arginine. Electrophoresis in the presence of beta-mercaptoethanol plus Na dodecyl-SO4 gave a single band (Mr, 54,000). Specific activity of this enzyme was 58.8 mumol of L-citrulline formed per min per mg of protein at 37 degrees. The optimum pH of the purified enzyme was 6.0 and maximal activity was obtained at 50 degrees. The molecular weight of the native protein was 130,000 by gel filtration and 120,000 by sedimentation-equilibrium measurements. The spectrum of the pure enzyme showed absorption maximum at 280 nm and the value of E-1%-1 CM AT 280 NM WAS 10.48 IN 0.05 M potassium phosphate buffer (pH 7.0). The crystalline enzyme hydrolyzed several L-arginine analogues. L-Homoarginine, L-alpha-amino-gamma-guanidinobutyric acid, and L-alpha-amino-beta-guanidinopropionic acid competitively inhibited the hydrolysis of L-arginine with Ki values of 25.7, 7.5, and 4.0 times 10- minus 3 M, respectively. p-Chloromercuribenzoate, Ag-+, and Hg-2+, and several metal ions inhibited the enzyme."}
{"id": "PMID:237905", "title": "Identity of maleate-stimulated glutaminase with gamma-glutamyl transpeptidase in rat kidney.", "content": "Gamma-Glutamyl transpeptidase was purified from rat kidney by a procedure involving Lubrol extraction, acetone precipitation, ammonium sulfate fractionation, treatment with bromelain, and column chromatography on DEAE-cellulose and Sephadex G-100. The final preparation (enzyme III), which exhibits a specific activity about 8-fold higher than that of the purified rat kidney transpeptidase previously obtained in this laboratory (enzyme I), was apparently homogeneous on polyacrylamide gel electrophoresis. Enzyme III is a glycoprotein containing 10% hexose, 7% aminohexose, and 1.5% sialic acid; a tentative molecular weight value of about 70,000 was obtained by gel filtration. Enzyme III has a much lower molecular weight and a different amino acid and carbohydrate content than the less active rat kidney transpeptidase preparation previously obtained, but obtained, but the catalytic properties of these preparations are virtually identical. It is suggested that bromelain treatment may liberate the transpeptidase from a brush border complex that contains other proteins. An improved method is described for the isolation of the higher molecular weight form of the enzyme (enzyme I) in which affinity chromatography on concanavalin A-Sephrose is employed. The purified transpeptidase (enzyme III) is similar to the phosphate-independent maleate-stimulated glutaminase preparation obtained from rat kidney by Katunuma and colleagues with respect to amino acid and carbohydrate content, apparent molecular weight, and relative transpeptidase and maleate-stimulated \"glutaminase\" activities. Both of these enzyme preparations are much more active in transpeptidation reactions with glutathione and related gamma-glutamyl compounds than with glutamine. In the absence of maleate, the enzyme catalyzes the utilization of glutamine (by conversion to gamma-glutamylglutamine, glutamate, and ammonia) at about 2% of the rate observed for catalysis of transpeptidation between glutathione and glycylglycine; the utilization of glutamine occurs about 8 times more rapidly in the presence of 0.1 M maleate. The transpeptidation and maleate-stimulated glutaminase reactions catalyzed by both enzyme preprations are inhibited by 5 mM L-serine in the presence of 5 mM sodium borate. Studies on gamma-glutamyl transpeptidase and maleate-stimulated glutaminase in the kidneys of fetal rats, newborn rats, and rats after weaning showed parallel development of these activities. The evidence reported here and earlier work in this laboratory strongly support the conclusion that maleate-stimulated glutaminase activity is a catalytic function of gamma-glutamyl transpeptidase. The studies on the ontogeny of gamma-glutamyl transpeptidase and other data are considered in relation to the proposal that this enzyme is involved in amino acid and peptide transport. Its possible role in renal formation of ammonia is also discussed.", "contents": "Identity of maleate-stimulated glutaminase with gamma-glutamyl transpeptidase in rat kidney. Gamma-Glutamyl transpeptidase was purified from rat kidney by a procedure involving Lubrol extraction, acetone precipitation, ammonium sulfate fractionation, treatment with bromelain, and column chromatography on DEAE-cellulose and Sephadex G-100. The final preparation (enzyme III), which exhibits a specific activity about 8-fold higher than that of the purified rat kidney transpeptidase previously obtained in this laboratory (enzyme I), was apparently homogeneous on polyacrylamide gel electrophoresis. Enzyme III is a glycoprotein containing 10% hexose, 7% aminohexose, and 1.5% sialic acid; a tentative molecular weight value of about 70,000 was obtained by gel filtration. Enzyme III has a much lower molecular weight and a different amino acid and carbohydrate content than the less active rat kidney transpeptidase preparation previously obtained, but obtained, but the catalytic properties of these preparations are virtually identical. It is suggested that bromelain treatment may liberate the transpeptidase from a brush border complex that contains other proteins. An improved method is described for the isolation of the higher molecular weight form of the enzyme (enzyme I) in which affinity chromatography on concanavalin A-Sephrose is employed. The purified transpeptidase (enzyme III) is similar to the phosphate-independent maleate-stimulated glutaminase preparation obtained from rat kidney by Katunuma and colleagues with respect to amino acid and carbohydrate content, apparent molecular weight, and relative transpeptidase and maleate-stimulated \"glutaminase\" activities. Both of these enzyme preparations are much more active in transpeptidation reactions with glutathione and related gamma-glutamyl compounds than with glutamine. In the absence of maleate, the enzyme catalyzes the utilization of glutamine (by conversion to gamma-glutamylglutamine, glutamate, and ammonia) at about 2% of the rate observed for catalysis of transpeptidation between glutathione and glycylglycine; the utilization of glutamine occurs about 8 times more rapidly in the presence of 0.1 M maleate. The transpeptidation and maleate-stimulated glutaminase reactions catalyzed by both enzyme preprations are inhibited by 5 mM L-serine in the presence of 5 mM sodium borate. Studies on gamma-glutamyl transpeptidase and maleate-stimulated glutaminase in the kidneys of fetal rats, newborn rats, and rats after weaning showed parallel development of these activities. The evidence reported here and earlier work in this laboratory strongly support the conclusion that maleate-stimulated glutaminase activity is a catalytic function of gamma-glutamyl transpeptidase. The studies on the ontogeny of gamma-glutamyl transpeptidase and other data are considered in relation to the proposal that this enzyme is involved in amino acid and peptide transport. Its possible role in renal formation of ammonia is also discussed."}
{"id": "PMID:237906", "title": "The extended active site of guinea pig liver transglutaminase.", "content": "The catalytic activities of guinea pig liver transglutaminase toward glutamine-containing peptide derivatives of three series have been studied. These series include: (a) formylheptapeptides of the basic structure, HCO-GLY3-L-Gln-Gly3. A single L-leucine residue was systematically substituted for glycine at a different position in each peptide; (b) formyltripeptides of the basic structure, HCO-Gly-L-Gln-Gly. L-Leucine was substituted for glycine in each position and in both positions; (c) various N-acyl derivatives of the dipeptide, L-Gln-Gly. Comparison of the values of the kinetic constants for methylamine incorporation and for hydroxylamine incorporation with the peptide derivatives shows that the length of the peptide chain has a pronounced influence on catalysis, as does the position of the leucine residue in the longer chain peptide derivatives. The kcat/Km(app) values for each substrate calculated from data for methylamine incorporation and from those for hydroxylamine incorporation were found to be in good agreement. However, both the observed maximum velocity and the apparent Michaelis constant for each peptide derivative were significantly larger for hydroxylamine incorporation than for methylamine incorporation. Interpretation of these findings as evidence for a normal catalytic mechanism for each amine incorporation reaction and for the limiting nature of deacylation to methylamine is discussed. Two observations caution against such an interpretation. These are the significantly higher inhibitor constants found fo formylhexaglycine and for several other competitive inhibitors in the hydroxylamine incorporation reaction, and earlier findings of higher turnover values with hyroxylamine in cases were acylation appears to be limiting for methylamine incorporation. Methods of preparation, supporting analytical data and properties of the peptide intermediates, the peptides, and their derivatives used in this study are presented in the miniprint supplement immediately following this paper.", "contents": "The extended active site of guinea pig liver transglutaminase. The catalytic activities of guinea pig liver transglutaminase toward glutamine-containing peptide derivatives of three series have been studied. These series include: (a) formylheptapeptides of the basic structure, HCO-GLY3-L-Gln-Gly3. A single L-leucine residue was systematically substituted for glycine at a different position in each peptide; (b) formyltripeptides of the basic structure, HCO-Gly-L-Gln-Gly. L-Leucine was substituted for glycine in each position and in both positions; (c) various N-acyl derivatives of the dipeptide, L-Gln-Gly. Comparison of the values of the kinetic constants for methylamine incorporation and for hydroxylamine incorporation with the peptide derivatives shows that the length of the peptide chain has a pronounced influence on catalysis, as does the position of the leucine residue in the longer chain peptide derivatives. The kcat/Km(app) values for each substrate calculated from data for methylamine incorporation and from those for hydroxylamine incorporation were found to be in good agreement. However, both the observed maximum velocity and the apparent Michaelis constant for each peptide derivative were significantly larger for hydroxylamine incorporation than for methylamine incorporation. Interpretation of these findings as evidence for a normal catalytic mechanism for each amine incorporation reaction and for the limiting nature of deacylation to methylamine is discussed. Two observations caution against such an interpretation. These are the significantly higher inhibitor constants found fo formylhexaglycine and for several other competitive inhibitors in the hydroxylamine incorporation reaction, and earlier findings of higher turnover values with hyroxylamine in cases were acylation appears to be limiting for methylamine incorporation. Methods of preparation, supporting analytical data and properties of the peptide intermediates, the peptides, and their derivatives used in this study are presented in the miniprint supplement immediately following this paper."}
{"id": "PMID:237907", "title": "Glucose-sensitive adenylate cyclase in toluene-treated cells of Escherichia coli B.", "content": "Toluene treatment of Escherichia coli B makes it possible to measure adenylate cyclase activity directly using [alpha-32-P]-ATP as substrate. In contrast to French press extracts, the activity of adenylate cyclase in toluene-treated cells shows many of the characteristics of the enzyme seen in the intact cell. In both toluene-treated and intact cells the activity of adenylate cyclase is inhibited at least 85% by glucose, while in French press extracts the enzyme activity is much lower and is not sensitive to inhibition by glucose. In toluene-treated cells, glucose inhibits at 10 muM, and the effect is rapid in onset and readily reversible. The activity is not inhibited by glucose 6-phosphate suggesting that glucose is responsible for the inhibition. The measurement of the activity and sensitivity to glucose of adenylate cyclase in toluene-treated cells requires the presence of potassium phosphate in the assay medium. Since it does not increase the activity or sensitivity of the enzyme in the French press extract, it is suggested that potassium phosphate is required for the maintenance of cellular integrity necessary for the activity and sensitivity of adenylate cyclase.", "contents": "Glucose-sensitive adenylate cyclase in toluene-treated cells of Escherichia coli B. Toluene treatment of Escherichia coli B makes it possible to measure adenylate cyclase activity directly using [alpha-32-P]-ATP as substrate. In contrast to French press extracts, the activity of adenylate cyclase in toluene-treated cells shows many of the characteristics of the enzyme seen in the intact cell. In both toluene-treated and intact cells the activity of adenylate cyclase is inhibited at least 85% by glucose, while in French press extracts the enzyme activity is much lower and is not sensitive to inhibition by glucose. In toluene-treated cells, glucose inhibits at 10 muM, and the effect is rapid in onset and readily reversible. The activity is not inhibited by glucose 6-phosphate suggesting that glucose is responsible for the inhibition. The measurement of the activity and sensitivity to glucose of adenylate cyclase in toluene-treated cells requires the presence of potassium phosphate in the assay medium. Since it does not increase the activity or sensitivity of the enzyme in the French press extract, it is suggested that potassium phosphate is required for the maintenance of cellular integrity necessary for the activity and sensitivity of adenylate cyclase."}
{"id": "PMID:237908", "title": "Guanosine 3':5'-monophosphate-dependent protein kinase from bovine cerebellum. Purification and characterization.", "content": "Guanosine 3':5'-monophosphate (cyclic GMP)-dependent protein kinase was assayed with calf thymus histone as substrate and partially purified from the soluble fraction of bovine cerebellum. The enzyme was selectively activated by cyclic GMP at lower concentrations; the Ka value for cyclic GMP was 1.7 times 10- minus 8 M whereas that for adenosine 3':5'-monophosphate (cyclic AMP) was 1.0 times 10- minus 6 M. The Km value for ATP was 1.0 times 10- minus 5 M. A high concentration of Mg-2+ (100 mM) was needed for maximum stimulation by cyclic GMP and maximum reaction rate. The pH optimum was 7.5 to 8.0. The isoelectric point was pH 5.7. The molecular weight was about 140,000 as estimated by gel filtration. The enzyme was unable to activate muscle glycogen phosphorylase kinase, and was clearly distinguishable from cyclic AMP-dependent protein kinase in kinetic and catalytic properties. Comparative data on cyclic GMP-dependent and cyclic AMP-dependent protein kinases in this tissue are presented.", "contents": "Guanosine 3':5'-monophosphate-dependent protein kinase from bovine cerebellum. Purification and characterization. Guanosine 3':5'-monophosphate (cyclic GMP)-dependent protein kinase was assayed with calf thymus histone as substrate and partially purified from the soluble fraction of bovine cerebellum. The enzyme was selectively activated by cyclic GMP at lower concentrations; the Ka value for cyclic GMP was 1.7 times 10- minus 8 M whereas that for adenosine 3':5'-monophosphate (cyclic AMP) was 1.0 times 10- minus 6 M. The Km value for ATP was 1.0 times 10- minus 5 M. A high concentration of Mg-2+ (100 mM) was needed for maximum stimulation by cyclic GMP and maximum reaction rate. The pH optimum was 7.5 to 8.0. The isoelectric point was pH 5.7. The molecular weight was about 140,000 as estimated by gel filtration. The enzyme was unable to activate muscle glycogen phosphorylase kinase, and was clearly distinguishable from cyclic AMP-dependent protein kinase in kinetic and catalytic properties. Comparative data on cyclic GMP-dependent and cyclic AMP-dependent protein kinases in this tissue are presented."}
{"id": "PMID:237909", "title": "The in vitro biosynthesis of dhurrin, the cyanogenic glycoside of Sorghum bicolor.", "content": "A microsomal fraction from seedlings of Sorghum bicolor (Linn) Moench has been shown to catalyze the conversion of L-tyrosine to p-hydroxymandelonitrile via p-hydroxyphenylacetaldoxime. This transformation is consistent with the general pathway for cyanogenic glycoside biosynthesis proposed on the basis of in vivo experiments. When the microsomal fraction was combined with a protein fraction from the soluble portion of the cell and uridine diphosphate glucose, it was possible to demonstrate the synthesis of the cyanogenic glycoside dhurrin from L-tyrosine.", "contents": "The in vitro biosynthesis of dhurrin, the cyanogenic glycoside of Sorghum bicolor. A microsomal fraction from seedlings of Sorghum bicolor (Linn) Moench has been shown to catalyze the conversion of L-tyrosine to p-hydroxymandelonitrile via p-hydroxyphenylacetaldoxime. This transformation is consistent with the general pathway for cyanogenic glycoside biosynthesis proposed on the basis of in vivo experiments. When the microsomal fraction was combined with a protein fraction from the soluble portion of the cell and uridine diphosphate glucose, it was possible to demonstrate the synthesis of the cyanogenic glycoside dhurrin from L-tyrosine."}
{"id": "PMID:237910", "title": "Characterization of a polyriboadenylate polymerase from vaccinia virions.", "content": "A poly(A) polymerase with a molecular weight of approximately 80,000 containing 51,000 and 35,000 molecular weight subunits, was purified by affinity chromatography from vaccinia virus cores. The enzyme had a pH optimum of about 8.6, was dependent on divalent cations, and had considerably more activity with Mn-2+ than Mg-2+. At equimolar concentrations, other ribonucleoside triphosphates inhibited poly(A) polymerase activity by less than 10%; NaCl was extremely inhibitory at concentrations above 0.1 M. Under standard assay conditions, poly(A) polymerase activity was stimulated more than 10-fold by poly(C), but to small extent or not at all by other homopolyribonucleotides or natural RNA species unless they were first subjected to partial hydrolysis and alkaline phosphatase treatment. The ineffectiveness of most long polyribonucleotides was attributed to enzyme binding to internal regions. Short poly- or oligoribonucleotides prepared from natural or synthetic RNAs, except poly(G), exhibited similar priming abilities, and isotope transfer experiments indicated the covalent attachment of poly(A) to cytidylate, uridylate, and inosinate residues. Experiments with a series of uridylate oligomers indicated that the minimum effective primer length was four to six nucleotides. Partially digested DNA and short poly- and oligodeoxyribonucleotides of dT, dC, and dI, but not of dA and dG, also acted as effective primers for the poly(A) polymerase.", "contents": "Characterization of a polyriboadenylate polymerase from vaccinia virions. A poly(A) polymerase with a molecular weight of approximately 80,000 containing 51,000 and 35,000 molecular weight subunits, was purified by affinity chromatography from vaccinia virus cores. The enzyme had a pH optimum of about 8.6, was dependent on divalent cations, and had considerably more activity with Mn-2+ than Mg-2+. At equimolar concentrations, other ribonucleoside triphosphates inhibited poly(A) polymerase activity by less than 10%; NaCl was extremely inhibitory at concentrations above 0.1 M. Under standard assay conditions, poly(A) polymerase activity was stimulated more than 10-fold by poly(C), but to small extent or not at all by other homopolyribonucleotides or natural RNA species unless they were first subjected to partial hydrolysis and alkaline phosphatase treatment. The ineffectiveness of most long polyribonucleotides was attributed to enzyme binding to internal regions. Short poly- or oligoribonucleotides prepared from natural or synthetic RNAs, except poly(G), exhibited similar priming abilities, and isotope transfer experiments indicated the covalent attachment of poly(A) to cytidylate, uridylate, and inosinate residues. Experiments with a series of uridylate oligomers indicated that the minimum effective primer length was four to six nucleotides. Partially digested DNA and short poly- and oligodeoxyribonucleotides of dT, dC, and dI, but not of dA and dG, also acted as effective primers for the poly(A) polymerase."}
{"id": "PMID:237911", "title": "Purification and characterization of mouse kidney beta-glucuronidase.", "content": "Beta-Glucuronidase has been purified from mouse kidneys previously induced by gonadotrophin to a specific enzyme activity 15 times higher than the non-induced kidney. The purification procedure includes ultrasonication to solubilize the enzyme, acid and ammonium sulfate precipitations, gel filtration in Sephadex G-200, DEAE-ion exchange chromatography, and isoelectric focusing. The resulting product has a specific activity of 284,000 Fishman units/mg of protein, representing a 1,090-fold purification and is 17,000-fold higher than the level in the non-induced kidney. The purified beta-glucuronidase is apparently homogeneous by criteria of gel filtration, sodium dodecyl sulfate gel electrophoresis, and immunodiffusion. Characterization of the purified enzyme showed that it is identical with the lysosomal isoenzymic from electrophoretically, has subunit molecular weight of 74,000 (estimated by sodium dodecyl sulfate gel electrophoresis) and oligomer molecular weight of 300,000. The purified enzyme is stable at high temperature (up to 55 degrees) and at wide range of pH (from 4 to 11). It has a pH optimum for its activity at 4.7 and a Km of 1.18 times 10- minus 4 M. The purification and characterization of this enzyme from mouse kidney will have significance in the understanding of the molecular nature of the isoenzymes of beta-glucuronidase and will be useful in future studies on the mechanism of intracellular transport and distribution of this hydrolase.", "contents": "Purification and characterization of mouse kidney beta-glucuronidase. Beta-Glucuronidase has been purified from mouse kidneys previously induced by gonadotrophin to a specific enzyme activity 15 times higher than the non-induced kidney. The purification procedure includes ultrasonication to solubilize the enzyme, acid and ammonium sulfate precipitations, gel filtration in Sephadex G-200, DEAE-ion exchange chromatography, and isoelectric focusing. The resulting product has a specific activity of 284,000 Fishman units/mg of protein, representing a 1,090-fold purification and is 17,000-fold higher than the level in the non-induced kidney. The purified beta-glucuronidase is apparently homogeneous by criteria of gel filtration, sodium dodecyl sulfate gel electrophoresis, and immunodiffusion. Characterization of the purified enzyme showed that it is identical with the lysosomal isoenzymic from electrophoretically, has subunit molecular weight of 74,000 (estimated by sodium dodecyl sulfate gel electrophoresis) and oligomer molecular weight of 300,000. The purified enzyme is stable at high temperature (up to 55 degrees) and at wide range of pH (from 4 to 11). It has a pH optimum for its activity at 4.7 and a Km of 1.18 times 10- minus 4 M. The purification and characterization of this enzyme from mouse kidney will have significance in the understanding of the molecular nature of the isoenzymes of beta-glucuronidase and will be useful in future studies on the mechanism of intracellular transport and distribution of this hydrolase."}
{"id": "PMID:237912", "title": "Localization of particulate guanylate cyclase in plasma membranes and microsomes of rat liver.", "content": "The subcellular localization of guanylate cyclase was examined in rat liver. About 80% of the enzyme activity of homogenates was found in the soluble fraction. Particulate guanylate cyclase was localized in plasma membranes and microsomes. Crude nuclear and microsomal fractions were applied to discontinuous sucrose gradients, and the resulting fractions were examined for guanylate cyclase, various enzyme markers of cell components, and electron microscopy. Purified plasma membrane fractions obtained from either preparation had the highest specific activity of guanylate cyclase, 30 to 80 pmol/min/mg of protein, and the recovery and relative specific activity of guanylate cyclase paralleled that of 5'-nucleotidase and adenylate cyclase in these fractions. Significant amounts of guanylate cyclase, adenylate cyclase, 5'-nucleotidase, and glucose-6-phosphatase were recovered in purified preparation of microsomes. We cannot exclude the presence of guanylate cyclase in other cell components such as Golgi. The electron microscopic studies of fractions supported the biochemical studies with enzyme markers. Soluble guanylate cyclase had typical Michaelis-Menten kinetics with respect to GTP and had an apparent Km for GTP of 35 muM. Ca-2+ stimulated the soluble activity in the presence of low concentrations of Mn-2+. The properties of guanylate cyclase in plasma membranes and microsomes were similar except that Ca-2+ inhibited the activity associated with plasma membranes and had no effect on that of microsomes. Both particulate enzymes were allosteric in nature; double reciprocal plots of velocity versus GTP were not linear, and Hill coefficients for preparations of plasma membranes and microsomes were calculated to be 1.60 and 1.58, respectively. The soluble and particulate enzymes were inhibited by ATP, and inhibition of the soluble enzyme was slightly greater. While Mg-2+ was less effective than Mn-2+ as a sole cation, all enzyme fractions were markedly stimulated with Mg-2+ in the presence of a low concentration of Mn-2+. Triton X-100 increased the activity of particulate fractions about 3- to 10-fold and increased the soluble activity 50 to 100%.", "contents": "Localization of particulate guanylate cyclase in plasma membranes and microsomes of rat liver. The subcellular localization of guanylate cyclase was examined in rat liver. About 80% of the enzyme activity of homogenates was found in the soluble fraction. Particulate guanylate cyclase was localized in plasma membranes and microsomes. Crude nuclear and microsomal fractions were applied to discontinuous sucrose gradients, and the resulting fractions were examined for guanylate cyclase, various enzyme markers of cell components, and electron microscopy. Purified plasma membrane fractions obtained from either preparation had the highest specific activity of guanylate cyclase, 30 to 80 pmol/min/mg of protein, and the recovery and relative specific activity of guanylate cyclase paralleled that of 5'-nucleotidase and adenylate cyclase in these fractions. Significant amounts of guanylate cyclase, adenylate cyclase, 5'-nucleotidase, and glucose-6-phosphatase were recovered in purified preparation of microsomes. We cannot exclude the presence of guanylate cyclase in other cell components such as Golgi. The electron microscopic studies of fractions supported the biochemical studies with enzyme markers. Soluble guanylate cyclase had typical Michaelis-Menten kinetics with respect to GTP and had an apparent Km for GTP of 35 muM. Ca-2+ stimulated the soluble activity in the presence of low concentrations of Mn-2+. The properties of guanylate cyclase in plasma membranes and microsomes were similar except that Ca-2+ inhibited the activity associated with plasma membranes and had no effect on that of microsomes. Both particulate enzymes were allosteric in nature; double reciprocal plots of velocity versus GTP were not linear, and Hill coefficients for preparations of plasma membranes and microsomes were calculated to be 1.60 and 1.58, respectively. The soluble and particulate enzymes were inhibited by ATP, and inhibition of the soluble enzyme was slightly greater. While Mg-2+ was less effective than Mn-2+ as a sole cation, all enzyme fractions were markedly stimulated with Mg-2+ in the presence of a low concentration of Mn-2+. Triton X-100 increased the activity of particulate fractions about 3- to 10-fold and increased the soluble activity 50 to 100%."}
{"id": "PMID:237913", "title": "Beta-Ketoacyl-acyl carrier protein synthetase.  Characterization of the acyl-enzyme intermediate.", "content": "Beta-Ketoacyl-acyl carrier protein (ACP) synthetase catalyzes the condensation reaction of fatty acid synthesis in Escherichia coli. The homogeneous enzyme reacts with hexanoyl-CoA to form hexanoyl-enzyme which was isolated and characterized. Hexanoyl-enzyme contains 2 mol of hexanoate/mol of enzyme (molecular weight 66,000); it is liable at alkaline pH, and it reacts with neutral hydroxylamine to form hexanoyl hydroxamic acid. Hexanoate was cleaved from the enzyme when hexanoyl-enzyme was subjected to performic acid oxidation. These properties indicate that hexanoyl-enzyme is a thioester. Studies of the circular dichroism spectra of fully acylated and nonacylated forms of the enzyme indicated that the secondary structure of the enzyme is relatively unperturbed by the presence of the hexanoyl groups. An alpha helical content of 65% was estimated for the enzyme from the circular dichroism spectrum. Hexanoyl-enzyme is active in both partial reactions that comprise the beta-ketoacyl-ACP synthetase reaction; it reacts with ACP to form hexanoyl-ACP and with malonyl-ACP to form beta-ketooctanoyl-ACP. Although the hexanoate of hexanoyl-enzyme is transferred very rapidly to ACP, the physiological acceptor in this reaction, it is also transferred very slowly to CoA, dithiothreitol, and 2-mercaptoethanol, indicating that the enzyme can react nonspecifically with a number of unrelated mercaptans.", "contents": "Beta-Ketoacyl-acyl carrier protein synthetase.  Characterization of the acyl-enzyme intermediate. Beta-Ketoacyl-acyl carrier protein (ACP) synthetase catalyzes the condensation reaction of fatty acid synthesis in Escherichia coli. The homogeneous enzyme reacts with hexanoyl-CoA to form hexanoyl-enzyme which was isolated and characterized. Hexanoyl-enzyme contains 2 mol of hexanoate/mol of enzyme (molecular weight 66,000); it is liable at alkaline pH, and it reacts with neutral hydroxylamine to form hexanoyl hydroxamic acid. Hexanoate was cleaved from the enzyme when hexanoyl-enzyme was subjected to performic acid oxidation. These properties indicate that hexanoyl-enzyme is a thioester. Studies of the circular dichroism spectra of fully acylated and nonacylated forms of the enzyme indicated that the secondary structure of the enzyme is relatively unperturbed by the presence of the hexanoyl groups. An alpha helical content of 65% was estimated for the enzyme from the circular dichroism spectrum. Hexanoyl-enzyme is active in both partial reactions that comprise the beta-ketoacyl-ACP synthetase reaction; it reacts with ACP to form hexanoyl-ACP and with malonyl-ACP to form beta-ketooctanoyl-ACP. Although the hexanoate of hexanoyl-enzyme is transferred very rapidly to ACP, the physiological acceptor in this reaction, it is also transferred very slowly to CoA, dithiothreitol, and 2-mercaptoethanol, indicating that the enzyme can react nonspecifically with a number of unrelated mercaptans."}
{"id": "PMID:237914", "title": "Multiple forms of beta-ketoacyl-acyl carrier protein synthetase in Escherichia coli.", "content": "Two forms of beta-ketoacyl-acyl carrier protein (ACP) synthetase (designated I and II) have been identified in extracts of Escherichia coli. Synthetase I corresponds to the condensing enzyme that was studied earlier (GREENSPAN, M.D., ALBERTS, A.W., and VAGELOS, P.R. (1969) J. Biol. Chem. 244, 6477-6485); synthetase II represents a new form of the enzyme. Synthetase II was isolated as a homogeneous protein. It differs from synthetase I in having a higher molecular weight (76,999 versus 66,000), a lower pH optimum (5.5 to 6.1 versus 7.2), and a greater resistance to denaturation by heat. Synthetase II is similar to synthetase I in that both are inactivated by iodoacetamide, and prior incubation of the enzymes with fatty acyl thioesters prevents the inhibitory effect of iodoacetamide. Both also react with a fatty acyl thioester to form an acyl-enzyme intermediate, and the latter reacts with malonyl-ACP to form a beta-ketoacyl thioester. Specificity studies indicated that synthetase II, like synthetase I, has similar affinities with saturated and cis unsaturated fatty acyl thioesters of ACP that are intermediates in the synthesis of saturated and unsaturated fatty acids, respectively. The two synthetases differ only with respect to reactivity with palmitoleyl thioesters: synthetase II has a lower Km and higher Vmax than synthetase I with palmitoleyl-ACP. This finding suggests that synthetase II functions specifically in the elongation of palmitoleyl-ACP to form cis-vaccenyl-ACP. An investigation of synthetases I and II in two classes of unsaturated fatty acid auxotrophs revealed that synthetase I is absent in one class, fabB. Addition of wild type synthetase I to fabB fatty acid synthetase, which synthesizes only saturated fatty acids, permitted this fatty acid synthetase to synthesize unsaturated fatty acids. These experiments indicate that synthetase I plays a critical role in the synthesis of unsaturated fatty acids.", "contents": "Multiple forms of beta-ketoacyl-acyl carrier protein synthetase in Escherichia coli. Two forms of beta-ketoacyl-acyl carrier protein (ACP) synthetase (designated I and II) have been identified in extracts of Escherichia coli. Synthetase I corresponds to the condensing enzyme that was studied earlier (GREENSPAN, M.D., ALBERTS, A.W., and VAGELOS, P.R. (1969) J. Biol. Chem. 244, 6477-6485); synthetase II represents a new form of the enzyme. Synthetase II was isolated as a homogeneous protein. It differs from synthetase I in having a higher molecular weight (76,999 versus 66,000), a lower pH optimum (5.5 to 6.1 versus 7.2), and a greater resistance to denaturation by heat. Synthetase II is similar to synthetase I in that both are inactivated by iodoacetamide, and prior incubation of the enzymes with fatty acyl thioesters prevents the inhibitory effect of iodoacetamide. Both also react with a fatty acyl thioester to form an acyl-enzyme intermediate, and the latter reacts with malonyl-ACP to form a beta-ketoacyl thioester. Specificity studies indicated that synthetase II, like synthetase I, has similar affinities with saturated and cis unsaturated fatty acyl thioesters of ACP that are intermediates in the synthesis of saturated and unsaturated fatty acids, respectively. The two synthetases differ only with respect to reactivity with palmitoleyl thioesters: synthetase II has a lower Km and higher Vmax than synthetase I with palmitoleyl-ACP. This finding suggests that synthetase II functions specifically in the elongation of palmitoleyl-ACP to form cis-vaccenyl-ACP. An investigation of synthetases I and II in two classes of unsaturated fatty acid auxotrophs revealed that synthetase I is absent in one class, fabB. Addition of wild type synthetase I to fabB fatty acid synthetase, which synthesizes only saturated fatty acids, permitted this fatty acid synthetase to synthesize unsaturated fatty acids. These experiments indicate that synthetase I plays a critical role in the synthesis of unsaturated fatty acids."}
{"id": "PMID:237915", "title": "Intermediates and enzymes between alpha-ketoarginine and gamma-guanidinobutyrate in the L-arginine catabolic pathway of Pseudomonas putida.", "content": "In Pseudomonas putida P2 grown on L-arginine as the sole source of carbon and nitrogen, catabolism of L-arginine forms of alpha-ketoarginine, gamma-guanidinobutyrate, and gamma-aminobutyrate. A previously undetected intermediate, gamma-guanidinobutyraldehyde, is identified as the product of alpha-ketoarginine decarboxylase. An 86-fold purification of this enzyme is described. Activity is thiamine pyrophosphate-dependent and cofactor reassociation is facilitated by divalent cations. The order of effectiveness is Mn-2+ greater than Mg-2+, Co-2+ greater than Ca-2+ greater than Ni-2+ greater than Zn-2+. An inducible enzyme that catalyzes conversion of gamma-guanidinobutyraldehyde to gamma-guanidinobutyrate has been studied in cell-free extracts. NAD-+, but no other cofactors, is required. By differential nutritional growth experiments, 4 regulatory units for the L-arginine pathway are proposed and inducers of 2 units are identified.", "contents": "Intermediates and enzymes between alpha-ketoarginine and gamma-guanidinobutyrate in the L-arginine catabolic pathway of Pseudomonas putida. In Pseudomonas putida P2 grown on L-arginine as the sole source of carbon and nitrogen, catabolism of L-arginine forms of alpha-ketoarginine, gamma-guanidinobutyrate, and gamma-aminobutyrate. A previously undetected intermediate, gamma-guanidinobutyraldehyde, is identified as the product of alpha-ketoarginine decarboxylase. An 86-fold purification of this enzyme is described. Activity is thiamine pyrophosphate-dependent and cofactor reassociation is facilitated by divalent cations. The order of effectiveness is Mn-2+ greater than Mg-2+, Co-2+ greater than Ca-2+ greater than Ni-2+ greater than Zn-2+. An inducible enzyme that catalyzes conversion of gamma-guanidinobutyraldehyde to gamma-guanidinobutyrate has been studied in cell-free extracts. NAD-+, but no other cofactors, is required. By differential nutritional growth experiments, 4 regulatory units for the L-arginine pathway are proposed and inducers of 2 units are identified."}
{"id": "PMID:237916", "title": "Synthesis of adenosine triphosphate by an artificially imposed electrochemical proton gradient in bovine heart submitochondrial particles.", "content": "Submitochondrial particles subjected to an artificially imposed electrochemical proton gradient consisting of a pH gradient (acid to base transition) and membrane potential (low to high K-+ transition in the presence of valinomycin) catalyzed the net synthesis of 2.5 nmol of [-32P]ATP per mg of protein from ADP and 32-Pi.  Optimal reaction conditions included incubation of submitochondrial particles in malonate at pH 5.0 with valinomycin in the absence of added K-+, followed by a rapid transition to pH 7.5 and 100 mM K-+.  ATP synthesis continued for about 6 s and was sensitive to uncouplers or oligomycin but insensitive to inhibitors of electron transport.  Lower amounts of ATP were formed by either the pH gradient (25%) of K-+ gradient (15%) alone.  These results demonstrate that an electrochemical gradient of protons can drive the synthesis of ATP by reversal of the proton-translocating ATPase independent of electron transport.", "contents": "Synthesis of adenosine triphosphate by an artificially imposed electrochemical proton gradient in bovine heart submitochondrial particles. Submitochondrial particles subjected to an artificially imposed electrochemical proton gradient consisting of a pH gradient (acid to base transition) and membrane potential (low to high K-+ transition in the presence of valinomycin) catalyzed the net synthesis of 2.5 nmol of [-32P]ATP per mg of protein from ADP and 32-Pi.  Optimal reaction conditions included incubation of submitochondrial particles in malonate at pH 5.0 with valinomycin in the absence of added K-+, followed by a rapid transition to pH 7.5 and 100 mM K-+.  ATP synthesis continued for about 6 s and was sensitive to uncouplers or oligomycin but insensitive to inhibitors of electron transport.  Lower amounts of ATP were formed by either the pH gradient (25%) of K-+ gradient (15%) alone.  These results demonstrate that an electrochemical gradient of protons can drive the synthesis of ATP by reversal of the proton-translocating ATPase independent of electron transport."}
{"id": "PMID:237917", "title": "Reactions of pyrzdoxal 5'-phosphate, 6-aminocaproic acid, cysteine, and penicilamine. Models for reactions of Schiff base linkages in pyridoxal 5'-phosphate-requiring enymes.", "content": "Schiff base formation, transaldimination, and reaction with aminothiols are important reactions which occur on the surface of pyridoxal-P-requiring enzymes. As a first step in assessing the role of the protein in these reactions, models for these reactions were studied in the absence of enzyme at 25 degrees, gamma/2 0.28. The reaction of 6-aminocaproic acid with pyridoxal-P to form the Schiff base N6-(P-pyridoxylidene)-aminocaproic acid was studied as a model for formation of Schiff base on the holoenzyme...", "contents": "Reactions of pyrzdoxal 5'-phosphate, 6-aminocaproic acid, cysteine, and penicilamine. Models for reactions of Schiff base linkages in pyridoxal 5'-phosphate-requiring enymes. Schiff base formation, transaldimination, and reaction with aminothiols are important reactions which occur on the surface of pyridoxal-P-requiring enzymes. As a first step in assessing the role of the protein in these reactions, models for these reactions were studied in the absence of enzyme at 25 degrees, gamma/2 0.28. The reaction of 6-aminocaproic acid with pyridoxal-P to form the Schiff base N6-(P-pyridoxylidene)-aminocaproic acid was studied as a model for formation of Schiff base on the holoenzyme..."}
{"id": "PMID:237918", "title": "The binding of CO2 to human hemoglobin.", "content": "CO2-dissociation curves of concentrated human deoxy- and carbonmonoxyhemoglobin at 37 degrees, pH 7.6 to 7.0, PCO2 equal to 10 to 160 mm Hg, have been obtained by a rapid mixing and ion exchange technique.  The CO2-dissociation curves for deoxyhemogloblin can only be fitted by assuming two classes of binding sites for carbon dioxide.  The simplest way to account for the experimental data is to assume that the alpha-amino groups of the alpha and beta chains react with carbon dioxide with affinities that differ by at least a factor of 3.  No difference in reactivity with CO2 was found among the four terminal alpha-amino groups of carbonmonoxyhemoglobin.", "contents": "The binding of CO2 to human hemoglobin. CO2-dissociation curves of concentrated human deoxy- and carbonmonoxyhemoglobin at 37 degrees, pH 7.6 to 7.0, PCO2 equal to 10 to 160 mm Hg, have been obtained by a rapid mixing and ion exchange technique.  The CO2-dissociation curves for deoxyhemogloblin can only be fitted by assuming two classes of binding sites for carbon dioxide.  The simplest way to account for the experimental data is to assume that the alpha-amino groups of the alpha and beta chains react with carbon dioxide with affinities that differ by at least a factor of 3.  No difference in reactivity with CO2 was found among the four terminal alpha-amino groups of carbonmonoxyhemoglobin."}
{"id": "PMID:237919", "title": "Fatty acid biosynthesis in Erlich cells. The mechanism of short term control by exogenous free fatty acids.", "content": "We have examined the mechanism by which extracellular free fatty acids regulate fatty acid biosynthesis in Ehrlich ascites tumor cells. De novo biosynthesis in intact cells was inhibited by stearate greater than oleate greater than palmitate greater than linoleate. The amount of citrate and long chain acyl-CoA in the cells was not changed appreciably by the addition of free fatty acids to the incubation medium, indicating than free fatty acids do not regulate fatty acid biosynthesis by changing the total intracellular content of these metabolites. By measuring the incorporation of labeled free fatty acids into acyl-CoA, however, it was determined that the fatty acid composition of the acyl-CoA poolwas changed dramatically to reflect the composition of the exogenous free fatty acids. The relative inhibitory effects of different free fatty acids appear to depend on the ability of their acyl-CoA derivatives to regulate acyl-CoA carboxylase activity. The acyl-CoA concentration needed to produce 50% inhibition of purified Ehrlich cell carboxylase was found to be 0.68 mum for stearoyl-CoA, 1.6 mum for oleoyl-CoA, 2.2 mum for palmitoyl-CoA, 23 mum for myristoyl-CoA, 30 mum for lauroyl-CoA, and 37 mum for linoleoyl-CoA. In contrast to their effects on de novo synthesis, all of the free fatty acids added except stearate stimulated chain elongation in intact cells. Microsomal chain elongation, the major system for elongation in Ehrlich cells, also was regulated by the composition of the cellular acyl-CoA pool. Lauroyl-CoA, myristoyl-CoA, and palmitoyl-CoA were good substrates for elongation by isolated microsomes; oleoyl-CoA, and linoleoyl-CoA were intermediate; and stearoyl-CoA was a very poor substrate. We conclude that free fatty acids regulate fatty acid biosynthesis by changing the composition of the cellular acyl-CoA pool. These changes control the rate of malonyl-CoA production and, because of the acyl-CoA substrate specificity of the microsomal elongation system, modulate the amount of malonyl-CoA used for chain elongation.", "contents": "Fatty acid biosynthesis in Erlich cells. The mechanism of short term control by exogenous free fatty acids. We have examined the mechanism by which extracellular free fatty acids regulate fatty acid biosynthesis in Ehrlich ascites tumor cells. De novo biosynthesis in intact cells was inhibited by stearate greater than oleate greater than palmitate greater than linoleate. The amount of citrate and long chain acyl-CoA in the cells was not changed appreciably by the addition of free fatty acids to the incubation medium, indicating than free fatty acids do not regulate fatty acid biosynthesis by changing the total intracellular content of these metabolites. By measuring the incorporation of labeled free fatty acids into acyl-CoA, however, it was determined that the fatty acid composition of the acyl-CoA poolwas changed dramatically to reflect the composition of the exogenous free fatty acids. The relative inhibitory effects of different free fatty acids appear to depend on the ability of their acyl-CoA derivatives to regulate acyl-CoA carboxylase activity. The acyl-CoA concentration needed to produce 50% inhibition of purified Ehrlich cell carboxylase was found to be 0.68 mum for stearoyl-CoA, 1.6 mum for oleoyl-CoA, 2.2 mum for palmitoyl-CoA, 23 mum for myristoyl-CoA, 30 mum for lauroyl-CoA, and 37 mum for linoleoyl-CoA. In contrast to their effects on de novo synthesis, all of the free fatty acids added except stearate stimulated chain elongation in intact cells. Microsomal chain elongation, the major system for elongation in Ehrlich cells, also was regulated by the composition of the cellular acyl-CoA pool. Lauroyl-CoA, myristoyl-CoA, and palmitoyl-CoA were good substrates for elongation by isolated microsomes; oleoyl-CoA, and linoleoyl-CoA were intermediate; and stearoyl-CoA was a very poor substrate. We conclude that free fatty acids regulate fatty acid biosynthesis by changing the composition of the cellular acyl-CoA pool. These changes control the rate of malonyl-CoA production and, because of the acyl-CoA substrate specificity of the microsomal elongation system, modulate the amount of malonyl-CoA used for chain elongation."}
{"id": "PMID:237920", "title": "Catalytic competence, a new criterion for affinity labeling. Demonstration of the reversible enzymatic interconversion of estrone and estradiol-17 beta covalently bound to human placental estradiol-17 beta dehydrogenase.", "content": "Human placental estradiol-17beta dehydrogenase is rapidly inactivated upon treatment with 3-bromoacetoxyestrone. Pseudo-first order kinetic data are obtained and inactivation is accompanied  by incorporation of 1 mol of 3-acetoxyestrone/mol of subunit (Mr =34,000). Treatment of the inactivated enzyme with (4S)-[4-2H]DPNH results in the formation of covalently bound [17alpha-2H]estradiol-17beta, which can be released by hydrolysis and identified by gas chromatography-mass sepctrometry. When (4R)-[4-2H]DPNH was used, deuterium was not transferred. Thus, the normal stereochemistry of hydridetransfer is preserved for both partners. After treatment with p-mercuribenzoate, affinity-labeled estradiol-17beta dehyrogenase is no longer able to caralyze reduction its covalently bound estrone; in the presence of DPNH and native enzyme, however, reduction occurs, demonstrating that affinity-labeled enzyme can itself serve as subtrate for native estradiol-17beta dehydrogenase. The reversible enzymatic interconversion of covalently bound estrone was demonstrated using a transhydrogenase assay. The ability of an enzyme to catalyze its normal reaction with a covalently bound substrate is termed catalytic competence, and is considered to be a new criterion for affinity labeling.", "contents": "Catalytic competence, a new criterion for affinity labeling. Demonstration of the reversible enzymatic interconversion of estrone and estradiol-17 beta covalently bound to human placental estradiol-17 beta dehydrogenase. Human placental estradiol-17beta dehydrogenase is rapidly inactivated upon treatment with 3-bromoacetoxyestrone. Pseudo-first order kinetic data are obtained and inactivation is accompanied  by incorporation of 1 mol of 3-acetoxyestrone/mol of subunit (Mr =34,000). Treatment of the inactivated enzyme with (4S)-[4-2H]DPNH results in the formation of covalently bound [17alpha-2H]estradiol-17beta, which can be released by hydrolysis and identified by gas chromatography-mass sepctrometry. When (4R)-[4-2H]DPNH was used, deuterium was not transferred. Thus, the normal stereochemistry of hydridetransfer is preserved for both partners. After treatment with p-mercuribenzoate, affinity-labeled estradiol-17beta dehyrogenase is no longer able to caralyze reduction its covalently bound estrone; in the presence of DPNH and native enzyme, however, reduction occurs, demonstrating that affinity-labeled enzyme can itself serve as subtrate for native estradiol-17beta dehydrogenase. The reversible enzymatic interconversion of covalently bound estrone was demonstrated using a transhydrogenase assay. The ability of an enzyme to catalyze its normal reaction with a covalently bound substrate is termed catalytic competence, and is considered to be a new criterion for affinity labeling."}
{"id": "PMID:237921", "title": "Chemical modification of bovine heart mitochondrial malate dehydrogenase.  Selective modification of cysteine and histidine.", "content": "Bovine mitochondrial malate dehydrogenase (EC 1.1.1.37) was inactivated by the specific modifications of a single histidine residue upon reaction with iodoacetamide.  NADH protected against this loss of activity and reaction with the histidine residue, suggesting that the histidine is at the NADH binding site.  N-Ethylmaleimide also modified the enzyme by reacting with 1 sulfhydryl residue.  The reaction rate with N-ethylmaleimide was increased by decreasing the pH from neutrality or by the addition of urea.  NADH protected against the modification of the sulfhydryl group under all the conditions tested, again suggesting active site specificity for this inactivation.  This enzyme has a subunit weight of 33,000 and is a dimer.  The native malate dehydrogenase will bind only 1 mol of NADH and it is thus assumed that there is only a single active site per dimer.", "contents": "Chemical modification of bovine heart mitochondrial malate dehydrogenase.  Selective modification of cysteine and histidine. Bovine mitochondrial malate dehydrogenase (EC 1.1.1.37) was inactivated by the specific modifications of a single histidine residue upon reaction with iodoacetamide.  NADH protected against this loss of activity and reaction with the histidine residue, suggesting that the histidine is at the NADH binding site.  N-Ethylmaleimide also modified the enzyme by reacting with 1 sulfhydryl residue.  The reaction rate with N-ethylmaleimide was increased by decreasing the pH from neutrality or by the addition of urea.  NADH protected against the modification of the sulfhydryl group under all the conditions tested, again suggesting active site specificity for this inactivation.  This enzyme has a subunit weight of 33,000 and is a dimer.  The native malate dehydrogenase will bind only 1 mol of NADH and it is thus assumed that there is only a single active site per dimer."}
{"id": "PMID:237922", "title": "Purification and characterization of the flavoenzyme glutathione reductase from rat liver.", "content": "Glutathione reductase from rat liver has been purified greater than 5000-fold in a yield of 20%.  The molecular weights of the enzyme and its subunits were estimated to be 125,000 and 60,000, respectively, indicating that the native enzyme is a dimer.  The enzyme molecular contains 2 FAD molecules, which are reducible by NADPH, GSH or dithioerythritol.  The reduced flavin is instantaneously reoxidized by addition of GSSG.  The steady state kinetic data are consistent with a branching reaction mechanism previously proposed for glutathione reductase from yeast (MANNERVIK, B. (1973) Biochem. Biophy. Res. Commun. 53, 1151-1158).  This mechanism is also favored by the nonlinear inhibition pattern produced by NADP-+.  However, at low GSSG concentrations the rate equation can be approximated by that of a simple ping pong mechanism.  NADPH and the mixed disulfide of coenzyme A and GSH were about 10% as active as NADPH and GSSG, respectively, whereas some sulfenyl derivatives related to GSSG were less active as substrates.  The pH activity profiles of these substrates differed from that of the NADPH-GSSG substrate pair.", "contents": "Purification and characterization of the flavoenzyme glutathione reductase from rat liver. Glutathione reductase from rat liver has been purified greater than 5000-fold in a yield of 20%.  The molecular weights of the enzyme and its subunits were estimated to be 125,000 and 60,000, respectively, indicating that the native enzyme is a dimer.  The enzyme molecular contains 2 FAD molecules, which are reducible by NADPH, GSH or dithioerythritol.  The reduced flavin is instantaneously reoxidized by addition of GSSG.  The steady state kinetic data are consistent with a branching reaction mechanism previously proposed for glutathione reductase from yeast (MANNERVIK, B. (1973) Biochem. Biophy. Res. Commun. 53, 1151-1158).  This mechanism is also favored by the nonlinear inhibition pattern produced by NADP-+.  However, at low GSSG concentrations the rate equation can be approximated by that of a simple ping pong mechanism.  NADPH and the mixed disulfide of coenzyme A and GSH were about 10% as active as NADPH and GSSG, respectively, whereas some sulfenyl derivatives related to GSSG were less active as substrates.  The pH activity profiles of these substrates differed from that of the NADPH-GSSG substrate pair."}
{"id": "PMID:237923", "title": "Reaction heat variation with pH in formation of the trypsin-soybean inhibitor complex.", "content": "The heat of reaction between beta-trypsin and Kunitz soybean inhibitor (STI) hasbeen measured at 5 degrees and 25 degrees from pH 4 to 8.5.  Corresponding measuremenportion of tRNA-Gly2-GGA/G 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 tRNA-Gly2-GGA/G(nucleotide position 38).  Asecondary effect of this base substitution is the modification of the A residue directly adjacent to the 3' end of the anticodon of tRNA-Gly2-suA36(HA), suggesting that the enzymes responsible for this modification recognize the anticodon sequencesof prospective tRNA substrates.  The creation of a missense-suppressing tRNA, tRNA-Gly2-suA36(HA), by an alteration of the anticodon sequence of tRNA-Gly2-GGA/G 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 may be recognized by the glycyl-tRNA synthetase; the involvement of theanticodon region in the synthetase recognition process is supported by the greatly decreased rate of aminoacylation of tRNA-Gly2-suA36(HA).", "contents": "Reaction heat variation with pH in formation of the trypsin-soybean inhibitor complex. The heat of reaction between beta-trypsin and Kunitz soybean inhibitor (STI) hasbeen measured at 5 degrees and 25 degrees from pH 4 to 8.5.  Corresponding measuremenportion of tRNA-Gly2-GGA/G 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 tRNA-Gly2-GGA/G(nucleotide position 38).  Asecondary effect of this base substitution is the modification of the A residue directly adjacent to the 3' end of the anticodon of tRNA-Gly2-suA36(HA), suggesting that the enzymes responsible for this modification recognize the anticodon sequencesof prospective tRNA substrates.  The creation of a missense-suppressing tRNA, tRNA-Gly2-suA36(HA), by an alteration of the anticodon sequence of tRNA-Gly2-GGA/G 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 may be recognized by the glycyl-tRNA synthetase; the involvement of theanticodon region in the synthetase recognition process is supported by the greatly decreased rate of aminoacylation of tRNA-Gly2-suA36(HA)."}
{"id": "PMID:237924", "title": "Characterization of the deoxyribonucleic acid polymerase associated with Kilham rat virus.", "content": "Purified preparations of the parvovirus, Kilham rat virus, have associated with them a protein with DNA polymerase activity. The enzyme has been separated from the other two or three viral proteins and purified 63-fold. The viral associated enzyme was found in a single peak of DNA polymerase activity after chromatography on DEAE-cellulose, DNA-cellulose, and phosphocellulose columns. It shares some properties in common with the host cellular DNA polymerases, described in the preceding paper (Salzman, L.A., and McKerlie, L. (1975) J. Biol. Chem. 250, 5589-5595), but also has some important distinguishing characteristics. The Kilham rat virus-associated DNA polymerase has increased enzyme activity in the presence of 0.02 M KCl and has a strong preference for a synthetic DNA polymer containing deoxyadenylate and deoxythymidylate. The enzyme has a molecular weight of approximately 75,000 plus or minus 3,000 and appears to contain endonuclease activity.", "contents": "Characterization of the deoxyribonucleic acid polymerase associated with Kilham rat virus. Purified preparations of the parvovirus, Kilham rat virus, have associated with them a protein with DNA polymerase activity. The enzyme has been separated from the other two or three viral proteins and purified 63-fold. The viral associated enzyme was found in a single peak of DNA polymerase activity after chromatography on DEAE-cellulose, DNA-cellulose, and phosphocellulose columns. It shares some properties in common with the host cellular DNA polymerases, described in the preceding paper (Salzman, L.A., and McKerlie, L. (1975) J. Biol. Chem. 250, 5589-5595), but also has some important distinguishing characteristics. The Kilham rat virus-associated DNA polymerase has increased enzyme activity in the presence of 0.02 M KCl and has a strong preference for a synthetic DNA polymer containing deoxyadenylate and deoxythymidylate. The enzyme has a molecular weight of approximately 75,000 plus or minus 3,000 and appears to contain endonuclease activity."}
{"id": "PMID:237925", "title": "Nuclear and cytoplasmic deoxyribonucleic acid polymerases from rat nephroma cells.", "content": "We have examined the DNA polymerases found in a rat nephroma cell line. Using DEAE- and DNA-cellulose chromatography, we have found two major cytoplasmic DNA polymerases and one major and three minor DNA polymerases from the nucleus. The enzymes were all purified, characterized, and distinguished from each other by several criteria. The enzyme require, for maximal activity, a natural or synthetic double-stranded DNA, four deoxynucleoside, triphosphates, and magnesium. They are inhibited to varying degrees by sodium pyrophosphate, ethidium bromide, and rho-chloromercuribenzoate.", "contents": "Nuclear and cytoplasmic deoxyribonucleic acid polymerases from rat nephroma cells. We have examined the DNA polymerases found in a rat nephroma cell line. Using DEAE- and DNA-cellulose chromatography, we have found two major cytoplasmic DNA polymerases and one major and three minor DNA polymerases from the nucleus. The enzymes were all purified, characterized, and distinguished from each other by several criteria. The enzyme require, for maximal activity, a natural or synthetic double-stranded DNA, four deoxynucleoside, triphosphates, and magnesium. They are inhibited to varying degrees by sodium pyrophosphate, ethidium bromide, and rho-chloromercuribenzoate."}
{"id": "PMID:237926", "title": "A unique reactive residue in adenosine triphosphate phosphoribosyltransferase sensitive to five conformation and dissociation states.", "content": "Adenosine triphosphate phosphoribosyltransferase is inactivated rapidly by bulky alkylating reagents in a biphasic reaction.  The initial inactivation rate is dependent upon an optimal concentration of histidine and is more rapid at low enzyme concentrations and low ionic strength.  A histidine-free dimer form of the enzyme is the proposed reactive species.  The dimer is shown by ultraviolet difference spectroscopy to bind histidine about 1 order of magnitude more weakly than the hexameric form of the enzyme.  Alkylated enzyme is similar to native enzyme in dissociation and histidine-binding properties.  Native enzyme must exist at significant levels in at least five different conformational and dissociative states to account for the inactivation behavior.", "contents": "A unique reactive residue in adenosine triphosphate phosphoribosyltransferase sensitive to five conformation and dissociation states. Adenosine triphosphate phosphoribosyltransferase is inactivated rapidly by bulky alkylating reagents in a biphasic reaction.  The initial inactivation rate is dependent upon an optimal concentration of histidine and is more rapid at low enzyme concentrations and low ionic strength.  A histidine-free dimer form of the enzyme is the proposed reactive species.  The dimer is shown by ultraviolet difference spectroscopy to bind histidine about 1 order of magnitude more weakly than the hexameric form of the enzyme.  Alkylated enzyme is similar to native enzyme in dissociation and histidine-binding properties.  Native enzyme must exist at significant levels in at least five different conformational and dissociative states to account for the inactivation behavior."}
{"id": "PMID:237927", "title": "The effects of ionic conditions, temperature, and chemical modification on the fluorescence of myosin during the steady state of ATP hydrolysis.  A comparison of the fluorescnece and electron spin resonance spectra of the spin-labeled enzyme.", "content": "The ATP-induced enhancement of the intrinsic fluorescence of myosin and heavy meromyosin (HMM) that persists during the steady state of hydrolysis has been investigated. To compare the substrate-induced changes in fluorescence with those in the electron spin resonance spectrum of the spin-labeled enzyme, we studied the influence of temperature, pH, and ionic strength, as well as the effect of chemical modification (spin labeling) of the SH-1 sulfhydryl groups. Changing the pH between 6 and 9 does not affect the enhancement of fluorescence of myosin or HMM; changing the ionic strength, which could be studied only with HMM, also has no effect; and decreasing the temperature from 20 to 5 degrees slightly diminishes the enhancement with both myosin and HMM. Chemical modification with N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyl) iodoacetamide, which blocks the SH-1 thiol groups, reduces the enhancement of fluorescence, induces a strong dependence on ionic strength and pH, and substantially increases the dependence on temperature. The enhancement with labeled myosin or labeled HMM increases with increasing pH, ionic strength, and temperature, closely paralleling the effects of these parameters on the electron spin resonance spectrum of spin-labeled myosin (SEIDEL, J.C. and GERGELY, J. (1973) Arch. Biochem. Biophys. 158, 853), suggesting that the same molecular change, induced by ATP and associated with formation of the MADP-P1 complex, underlies both the change in fluorescence and the change in ESR spectrum. Those analogues of ATP that produce the maximal enhancement of fluorescence (WERBER, M., SZENT-GYORGYL, A.G., and FASMAN, G. (1972) Biochemistry 11, 2872) also produce the maximal change in the ESR spectra. Both an amino group at position 6 of the substrate and an unmodified triphosphate chain are required for maximal change in either fluorescence or ESR spectra. The smaller enhancement of fluorescence produced by spin labeling the SH-1 groups persists after the nitroxide has been chemically changed to a diamagnetic species. Thus the small enhancement cannot be attributed to paramagnetic quenching of tryptophan fluorescence by the spin label. An initial burst of phosphate liberation accompanies the hydrolysis of ATP, cytidine 5'-triphosphate, uridine 5'-triphosphate, guanosine 5'-tryphosphate, iosine 5'-triphosphate, 2'-deoxyadenosine 5'-tryphosphate, adenosine 5'-tetraphosphate, and tripolyphosphate. The presence or absence of the burst does not correlate with the extent of the spectral change.", "contents": "The effects of ionic conditions, temperature, and chemical modification on the fluorescence of myosin during the steady state of ATP hydrolysis.  A comparison of the fluorescnece and electron spin resonance spectra of the spin-labeled enzyme. The ATP-induced enhancement of the intrinsic fluorescence of myosin and heavy meromyosin (HMM) that persists during the steady state of hydrolysis has been investigated. To compare the substrate-induced changes in fluorescence with those in the electron spin resonance spectrum of the spin-labeled enzyme, we studied the influence of temperature, pH, and ionic strength, as well as the effect of chemical modification (spin labeling) of the SH-1 sulfhydryl groups. Changing the pH between 6 and 9 does not affect the enhancement of fluorescence of myosin or HMM; changing the ionic strength, which could be studied only with HMM, also has no effect; and decreasing the temperature from 20 to 5 degrees slightly diminishes the enhancement with both myosin and HMM. Chemical modification with N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyl) iodoacetamide, which blocks the SH-1 thiol groups, reduces the enhancement of fluorescence, induces a strong dependence on ionic strength and pH, and substantially increases the dependence on temperature. The enhancement with labeled myosin or labeled HMM increases with increasing pH, ionic strength, and temperature, closely paralleling the effects of these parameters on the electron spin resonance spectrum of spin-labeled myosin (SEIDEL, J.C. and GERGELY, J. (1973) Arch. Biochem. Biophys. 158, 853), suggesting that the same molecular change, induced by ATP and associated with formation of the MADP-P1 complex, underlies both the change in fluorescence and the change in ESR spectrum. Those analogues of ATP that produce the maximal enhancement of fluorescence (WERBER, M., SZENT-GYORGYL, A.G., and FASMAN, G. (1972) Biochemistry 11, 2872) also produce the maximal change in the ESR spectra. Both an amino group at position 6 of the substrate and an unmodified triphosphate chain are required for maximal change in either fluorescence or ESR spectra. The smaller enhancement of fluorescence produced by spin labeling the SH-1 groups persists after the nitroxide has been chemically changed to a diamagnetic species. Thus the small enhancement cannot be attributed to paramagnetic quenching of tryptophan fluorescence by the spin label. An initial burst of phosphate liberation accompanies the hydrolysis of ATP, cytidine 5'-triphosphate, uridine 5'-triphosphate, guanosine 5'-tryphosphate, iosine 5'-triphosphate, 2'-deoxyadenosine 5'-tryphosphate, adenosine 5'-tetraphosphate, and tripolyphosphate. The presence or absence of the burst does not correlate with the extent of the spectral change."}
{"id": "PMID:237928", "title": "Gram-negative osteomyelitis following puncture wounds of the foot.", "content": "Seven cases of gram-negative osteomyelitis following puncture wounds of the foot are presented. Regardless of age (range, five to thirty-two years) all patients had a similar, typical clinical picture of one to two weeks of improvement after the initial post-traumatic inflammation followed by worsening of the local signs. Two patients were successfully treated with antibiotics alone and five, with antibiotics in combination with curettage.", "contents": "Gram-negative osteomyelitis following puncture wounds of the foot. Seven cases of gram-negative osteomyelitis following puncture wounds of the foot are presented. Regardless of age (range, five to thirty-two years) all patients had a similar, typical clinical picture of one to two weeks of improvement after the initial post-traumatic inflammation followed by worsening of the local signs. Two patients were successfully treated with antibiotics alone and five, with antibiotics in combination with curettage."}
{"id": "PMID:237929", "title": "Effect of ploidy on spontaneous mutation rate to asparagine non-requirement in cultured cells.", "content": "Variations in ploidy do not affect the spontaneous mutation rate to asparagine non-requirement in Jensen rat sarcoma cells cultivated in vitro.", "contents": "Effect of ploidy on spontaneous mutation rate to asparagine non-requirement in cultured cells. Variations in ploidy do not affect the spontaneous mutation rate to asparagine non-requirement in Jensen rat sarcoma cells cultivated in vitro."}
{"id": "PMID:237930", "title": "Glucose utilization, pH reduction and density dependent inhibition in cultures of chick embryo fibroblasts.", "content": "The multiplication rate of sparse cultures of chick embryo cells is only slightly lower at pH 6.9 than at pH 7.4. There is, however, a marked reduction in the multiplication rate of the pH 6.9 cultures before they reach confluency. Cultures at pH 7.4 continue to multiply beyond confluency with only a slight decrease in the multiplication rate. Eighty to ninety percent of the glucose taken up by the cells growing at each pH is converted to lactic acid which is released into the medium. Metabolic reduction in pH of the medium is almost entirely accounted for by the amount of lactic acid produced by the cells. Neither the intracellular nor extracellular accumulation of lactic acid nor the accompanying reduction in pH is sufficient to explain density dependent inhibition of the rate of multiplication of chick cells. The rate of lactic acid production and the multiplication rate of chick cells are independent of glucose concentration in the range of 2--16 mM. In view of the kinetic parameters for the uptake of glucose, this shows that glycolysis is not limited by the rate of glucose uptake and that depletion of glucose from the medium cannot account for the onset of density dependent inhibition of multiplication. However, when cells reach very high population densities, conventional glucose concentrations of 5 mM can be depleted overnight by chick cells. Since the multiplication rate of cells is dependent on glucose concentration when it falls below 2 mM, depletion of glucose may cause some growth inhibition in crowded cultures supplied with conventional medium.", "contents": "Glucose utilization, pH reduction and density dependent inhibition in cultures of chick embryo fibroblasts. The multiplication rate of sparse cultures of chick embryo cells is only slightly lower at pH 6.9 than at pH 7.4. There is, however, a marked reduction in the multiplication rate of the pH 6.9 cultures before they reach confluency. Cultures at pH 7.4 continue to multiply beyond confluency with only a slight decrease in the multiplication rate. Eighty to ninety percent of the glucose taken up by the cells growing at each pH is converted to lactic acid which is released into the medium. Metabolic reduction in pH of the medium is almost entirely accounted for by the amount of lactic acid produced by the cells. Neither the intracellular nor extracellular accumulation of lactic acid nor the accompanying reduction in pH is sufficient to explain density dependent inhibition of the rate of multiplication of chick cells. The rate of lactic acid production and the multiplication rate of chick cells are independent of glucose concentration in the range of 2--16 mM. In view of the kinetic parameters for the uptake of glucose, this shows that glycolysis is not limited by the rate of glucose uptake and that depletion of glucose from the medium cannot account for the onset of density dependent inhibition of multiplication. However, when cells reach very high population densities, conventional glucose concentrations of 5 mM can be depleted overnight by chick cells. Since the multiplication rate of cells is dependent on glucose concentration when it falls below 2 mM, depletion of glucose may cause some growth inhibition in crowded cultures supplied with conventional medium."}
{"id": "PMID:237931", "title": "Cytoplasmic streaming in Chara: a cell model activated by ATP and inhibited by cytochalasin B.", "content": "After vacuolar perfusion of Chara internode cells, the cytoplasm remaining in situ can be reactivated by ATP to give full rates of streaming. Observations during both perfusion and reactivation indicated that the generation of the motive force was associated with fibres consisting of bundles of microfilaments. In the absence of ATP, the remaining endoplasmic organelles were immobilized along such fibres. When ATP was introduced, organelles moved along the fibres at speeds up to 50 mum S minus 1, but but were progressively released from contact to leave the fibres in a conspicuously clean state. Inorganic pyrophosphate freed the organelles from the fibres without supporting movements. Motility required millimolar Mg2nlevels, free Ca2nat 10 minus 7 M or less and was inhibited by high levels of Clminus and by pH's on either side of 7.0. The reactivated movements were rapidly and completely inhibited by 25mug ml minus 1 cytochalasin B. The results are interpreted in terms of actin filaments in the stationary cortex interacting with a myosin-like protein which is able to link to endoplasmic organelles. Movement results from an active shear type of mechanism.", "contents": "Cytoplasmic streaming in Chara: a cell model activated by ATP and inhibited by cytochalasin B. After vacuolar perfusion of Chara internode cells, the cytoplasm remaining in situ can be reactivated by ATP to give full rates of streaming. Observations during both perfusion and reactivation indicated that the generation of the motive force was associated with fibres consisting of bundles of microfilaments. In the absence of ATP, the remaining endoplasmic organelles were immobilized along such fibres. When ATP was introduced, organelles moved along the fibres at speeds up to 50 mum S minus 1, but but were progressively released from contact to leave the fibres in a conspicuously clean state. Inorganic pyrophosphate freed the organelles from the fibres without supporting movements. Motility required millimolar Mg2nlevels, free Ca2nat 10 minus 7 M or less and was inhibited by high levels of Clminus and by pH's on either side of 7.0. The reactivated movements were rapidly and completely inhibited by 25mug ml minus 1 cytochalasin B. The results are interpreted in terms of actin filaments in the stationary cortex interacting with a myosin-like protein which is able to link to endoplasmic organelles. Movement results from an active shear type of mechanism."}
{"id": "PMID:237934", "title": "Chromatographic analysis of the neutral and phosphatide glyceryl ethers from various biological sources.", "content": "A method of analysis is described which permits the facile evaluation of the neutral glyceryl ether lipids (mild alkaline hydrolysis) and total glyceryl ether lipid (Vitride reduction) thereby allowing an assessment of the phosphatide contribution. The alkyl and alk-enyl glyceryl ethers are chromatographically resolvable on Gelman glass-fiber type SG and Whatman SG-81 and detected by the periodic acid-Schiff and plasmal reaction, respectively. The attending problems and interpretation are discussed with examples from a number of unicellular organisms and animal tissues.", "contents": "Chromatographic analysis of the neutral and phosphatide glyceryl ethers from various biological sources. A method of analysis is described which permits the facile evaluation of the neutral glyceryl ether lipids (mild alkaline hydrolysis) and total glyceryl ether lipid (Vitride reduction) thereby allowing an assessment of the phosphatide contribution. The alkyl and alk-enyl glyceryl ethers are chromatographically resolvable on Gelman glass-fiber type SG and Whatman SG-81 and detected by the periodic acid-Schiff and plasmal reaction, respectively. The attending problems and interpretation are discussed with examples from a number of unicellular organisms and animal tissues."}
{"id": "PMID:237935", "title": "Ion-exclusion chromatography of compounds of biological interest.", "content": "The principle of ion exclusion was examined as a method for the separation of small ionic compounds. The systems employed consisted of very porous column packings, substituted with fixed charges, which were eluted by buffer solutions of low ionic strength. DEAE-Sephadex A-50 was principally employed, and it was shown that there was a linear relationship between the net charge on a cation and its partition coefficient into the gel phase. A similar relationship existed in the chromatography of amino acids on various columns bearing fixed negative charges. It was concluded that this was an efficient form of chromatography, which gave results directly related to the ionic charge of the sample being examined. The charge characteristics of biologically active compound could be determined by this method.", "contents": "Ion-exclusion chromatography of compounds of biological interest. The principle of ion exclusion was examined as a method for the separation of small ionic compounds. The systems employed consisted of very porous column packings, substituted with fixed charges, which were eluted by buffer solutions of low ionic strength. DEAE-Sephadex A-50 was principally employed, and it was shown that there was a linear relationship between the net charge on a cation and its partition coefficient into the gel phase. A similar relationship existed in the chromatography of amino acids on various columns bearing fixed negative charges. It was concluded that this was an efficient form of chromatography, which gave results directly related to the ionic charge of the sample being examined. The charge characteristics of biologically active compound could be determined by this method."}
{"id": "PMID:237936", "title": "Identification of glucagon in the gastrointestinal tract.", "content": "Gel filtration studies on Bio-Gel P-10 columns of a 50-fold purified porcine duodenal extract revealed a main peak of glucagon-like immunoreactivity (GLI) in the 2,900 mol wt zone and a smaller peak in the 3,500 mol wt zone, the same zone as the pancreatic glucagon marker. Like pancreatic glucagon, samples of 3,500 mol wt material gave essentially identical measurements in radioimmunoassays employing the pancreatic glucagon-specific antiserum 30K and the GLI crossreacting antiserum 78J, whereas the 2,900 mol wt peptide gave 60-fold higher readings in the 78J assay. On disk gel electrophoresis, the 3,500 mol wt fraction, like pancreatic glucagon, migrated at pH 8.3, whereas the 2,900 mol wt peptide remained at the origin; at pH 4.7, the 2,900 mol wt peptide migrated while the 3,500 mol wt immunoreactive peptide and glucagon remained at the origin. Isoelectric focusing revealed the 3,500 mol wt moiety to have an isoelectric point (pI) of 6.2, the same as pancreatic glucagon, whereas the 2,900 mol wt peptide had an pI greater than 10. The glycogenolytic activity of the 3,500 mol wt peptide in the perfused rat liver did not differ significantly from glucagon, and its adenylate cyclase stimulating activity in partially purified liver cell membranes was comparable to that of glucagon; the 2,900 mol wt peptide had less than 20% of these activities. In samples of 3,500 mol wt material subjected to isoelectric focusing, adenylate cyclase-stimulating activity was confirmed to fractions containing 30K immunoreactivity with a pI of 6.2. In samples of 2,900 mol wt material subjected to isoelectric focusing, adenylate cyclase-stimulating activity was confined to fractions containing 78J immunoreactivity with an pI greater than 10. Displacement of [125-I]glucagon from the membranes was limited to these two biologically active fractions. However, the affinity of both pancreatic glucagon and the 3,500 mol wt peptide was an order of magnitude greater than of the 2,900 mol wt peptide. Thus, by all of several biologic, physiocochemical, and immunometric techniques, the 3,500 mol wt gut immunoreactive peptide could not be distinguished from pancreatic glucagon, while the 2,900 mol wt peptide was readily differentiated by all these techniques. \"True\" A-cells, ultrastructurally indistinguishable from pancreatic A-cells but differing from the A-like cells of the lower bowel, were identified in the gastric fundus of dogs. Their distribution corresponded to that of the 3,500 mol wt immunoreactivity resembling pancreatic glucagon, while the distribution of \"A-like cells\" in the lower small intestine corresponded to that of GLI.", "contents": "Identification of glucagon in the gastrointestinal tract. Gel filtration studies on Bio-Gel P-10 columns of a 50-fold purified porcine duodenal extract revealed a main peak of glucagon-like immunoreactivity (GLI) in the 2,900 mol wt zone and a smaller peak in the 3,500 mol wt zone, the same zone as the pancreatic glucagon marker. Like pancreatic glucagon, samples of 3,500 mol wt material gave essentially identical measurements in radioimmunoassays employing the pancreatic glucagon-specific antiserum 30K and the GLI crossreacting antiserum 78J, whereas the 2,900 mol wt peptide gave 60-fold higher readings in the 78J assay. On disk gel electrophoresis, the 3,500 mol wt fraction, like pancreatic glucagon, migrated at pH 8.3, whereas the 2,900 mol wt peptide remained at the origin; at pH 4.7, the 2,900 mol wt peptide migrated while the 3,500 mol wt immunoreactive peptide and glucagon remained at the origin. Isoelectric focusing revealed the 3,500 mol wt moiety to have an isoelectric point (pI) of 6.2, the same as pancreatic glucagon, whereas the 2,900 mol wt peptide had an pI greater than 10. The glycogenolytic activity of the 3,500 mol wt peptide in the perfused rat liver did not differ significantly from glucagon, and its adenylate cyclase stimulating activity in partially purified liver cell membranes was comparable to that of glucagon; the 2,900 mol wt peptide had less than 20% of these activities. In samples of 3,500 mol wt material subjected to isoelectric focusing, adenylate cyclase-stimulating activity was confirmed to fractions containing 30K immunoreactivity with a pI of 6.2. In samples of 2,900 mol wt material subjected to isoelectric focusing, adenylate cyclase-stimulating activity was confined to fractions containing 78J immunoreactivity with an pI greater than 10. Displacement of [125-I]glucagon from the membranes was limited to these two biologically active fractions. However, the affinity of both pancreatic glucagon and the 3,500 mol wt peptide was an order of magnitude greater than of the 2,900 mol wt peptide. Thus, by all of several biologic, physiocochemical, and immunometric techniques, the 3,500 mol wt gut immunoreactive peptide could not be distinguished from pancreatic glucagon, while the 2,900 mol wt peptide was readily differentiated by all these techniques. \"True\" A-cells, ultrastructurally indistinguishable from pancreatic A-cells but differing from the A-like cells of the lower bowel, were identified in the gastric fundus of dogs. Their distribution corresponded to that of the 3,500 mol wt immunoreactivity resembling pancreatic glucagon, while the distribution of \"A-like cells\" in the lower small intestine corresponded to that of GLI."}
{"id": "PMID:237937", "title": "The acetylation of hemoglobin by aspirin.  In vitro and in vivo.", "content": "The chemical modification of hemoglobin by aspirin (ASA) has been studied, both in intact human red cells and in purified hemoglobin solutions. After incubation of red cells with 20 mM [acetyl-1minus14C]ASA, incorporation of radioactivity into hemoglobin was observed in agreement with the results of Klotz and Tam (1973. Proc. Natl. Acad. Sci. U. S. A. 70: 1313-1315). In contrast, no labeling of hemoglobin was seen when [carbosyl-14-C]ASA was used. These results indicate that ASA acetylates hemoglobin. The acetylated hemoglobin was readily separated from unmodified hemoglobin by both gel electrofocusing and by column chromatography. Quantitation of the extent of acetylation by densitometric scanning of gels agreed very well with estimates obtained from radioactivity measurements. Hemolysates prepared from red cells incubated with ASA showed normal oxygen affinity and heme-heme interaction. Purified acetylated hemoglobin had a slightly increased oxygen affinity and decreased heme-heme interaction. There was no difference in the rate of acetylation of oxy- and deoxyhemoglobin. ASA acetylated column-purified hemoglobin A more readily than hemoglobin in crude hemolysate, but less rapidly than purified human serum albumin. The rate of acetylation of hemoglobulin increased with pH up to approximately pH 8,5. Structural studies were done on hemoglobin incubated with 2.0 mM and 20 mM [acetyl-1-14-C]ASA. Alpha- and beta-chains were acetylated almost equally. Tryptic digests of purified acetylated subunits were fingerprinted on cellulose thin layer plates and autoradiographed. Both alpha- and beta-chains showed a number of radioactive spots that were either ninhydrin negative or weakly ninhydrin positive. These results indicate that hemoglobin is acetylated at a number of sites, probably at the epislon-amino group of lysine residues. To determine whether ASA acetylates hemoglobin in vivo, hemolysates of 14 patients on long-term high-dose ASA therapy were analyzed by gel electrofocusing and compared to specimens of individuals not receiving ASA. The ASA-treated group had a twofold increase in a minor hemoglobin component having an isoelectric point lower than that of hemoglobin A, and indistinguishable from the minoe component which appears when hemoglobin is incubated with ASA in vitro.", "contents": "The acetylation of hemoglobin by aspirin.  In vitro and in vivo. The chemical modification of hemoglobin by aspirin (ASA) has been studied, both in intact human red cells and in purified hemoglobin solutions. After incubation of red cells with 20 mM [acetyl-1minus14C]ASA, incorporation of radioactivity into hemoglobin was observed in agreement with the results of Klotz and Tam (1973. Proc. Natl. Acad. Sci. U. S. A. 70: 1313-1315). In contrast, no labeling of hemoglobin was seen when [carbosyl-14-C]ASA was used. These results indicate that ASA acetylates hemoglobin. The acetylated hemoglobin was readily separated from unmodified hemoglobin by both gel electrofocusing and by column chromatography. Quantitation of the extent of acetylation by densitometric scanning of gels agreed very well with estimates obtained from radioactivity measurements. Hemolysates prepared from red cells incubated with ASA showed normal oxygen affinity and heme-heme interaction. Purified acetylated hemoglobin had a slightly increased oxygen affinity and decreased heme-heme interaction. There was no difference in the rate of acetylation of oxy- and deoxyhemoglobin. ASA acetylated column-purified hemoglobin A more readily than hemoglobin in crude hemolysate, but less rapidly than purified human serum albumin. The rate of acetylation of hemoglobulin increased with pH up to approximately pH 8,5. Structural studies were done on hemoglobin incubated with 2.0 mM and 20 mM [acetyl-1-14-C]ASA. Alpha- and beta-chains were acetylated almost equally. Tryptic digests of purified acetylated subunits were fingerprinted on cellulose thin layer plates and autoradiographed. Both alpha- and beta-chains showed a number of radioactive spots that were either ninhydrin negative or weakly ninhydrin positive. These results indicate that hemoglobin is acetylated at a number of sites, probably at the epislon-amino group of lysine residues. To determine whether ASA acetylates hemoglobin in vivo, hemolysates of 14 patients on long-term high-dose ASA therapy were analyzed by gel electrofocusing and compared to specimens of individuals not receiving ASA. The ASA-treated group had a twofold increase in a minor hemoglobin component having an isoelectric point lower than that of hemoglobin A, and indistinguishable from the minoe component which appears when hemoglobin is incubated with ASA in vitro."}
{"id": "PMID:237938", "title": "An alternative pathway for fibrinolysis.  I. The cleavage of fibrinogen by leukocyte proteases at physiologic pH.", "content": "An alternative fibrinolytic system, active at physiological pH, is present in peripheral blood leukocytes. The fibrinolytic proteases localized predominantly in the leukocyte granules are capable of degrading both fibrinogen and fibrin, and plasmin activity does not contribute significantly to this proteolytic event. The specificity of the alternative fibrinolytic proteases for fibrinogen and the characteristics of the derivative cleavage fragments are clearly distinguishable from the classical plasmin system. The high molecular weight derivatives of fibrinogen, generated by the alternative system, under physiological conditions, are larger than the plasmin-generated X fragment, exhibit immunoelectrophoretic mobility comparable to native fibrinogen, and are not coagulable by thrombin. Analysis of the constituent polypeptide chains of the fragments reveals cleavage of the Aalpha, Bbeta, and gamma chains of fibrinogen. The lower molecular weight derivatives of fibrinogen, generated by the alternative system, are structurally distinct from previously described fibrinogen degradation products and exhibit potent anticoagulant activity. This anticoagulant activity can be attributed to interference with normal fibrin polymerization. The proteases of the alternative fibrinolytic systems are actively secreted by leukocytes when stimulated to undergo a nonlytic release reaction. These results provide direct evidence for a fibrinolytic system resident in leukocyte granules that is associated with the leukocyte release reaction and is capable of generating unique fibrinogen cleavage fragments.", "contents": "An alternative pathway for fibrinolysis.  I. The cleavage of fibrinogen by leukocyte proteases at physiologic pH. An alternative fibrinolytic system, active at physiological pH, is present in peripheral blood leukocytes. The fibrinolytic proteases localized predominantly in the leukocyte granules are capable of degrading both fibrinogen and fibrin, and plasmin activity does not contribute significantly to this proteolytic event. The specificity of the alternative fibrinolytic proteases for fibrinogen and the characteristics of the derivative cleavage fragments are clearly distinguishable from the classical plasmin system. The high molecular weight derivatives of fibrinogen, generated by the alternative system, under physiological conditions, are larger than the plasmin-generated X fragment, exhibit immunoelectrophoretic mobility comparable to native fibrinogen, and are not coagulable by thrombin. Analysis of the constituent polypeptide chains of the fragments reveals cleavage of the Aalpha, Bbeta, and gamma chains of fibrinogen. The lower molecular weight derivatives of fibrinogen, generated by the alternative system, are structurally distinct from previously described fibrinogen degradation products and exhibit potent anticoagulant activity. This anticoagulant activity can be attributed to interference with normal fibrin polymerization. The proteases of the alternative fibrinolytic systems are actively secreted by leukocytes when stimulated to undergo a nonlytic release reaction. These results provide direct evidence for a fibrinolytic system resident in leukocyte granules that is associated with the leukocyte release reaction and is capable of generating unique fibrinogen cleavage fragments."}
{"id": "PMID:237940", "title": "Tributyrate as a substrate for the determination of lipase activity in milk.", "content": "A procedure is described for the determination of the lipolytic activity in milk using tributyrate as substrate. The method is based on the titration of liberated butyric acid in a diethyl ether: light petroleum (2-75:1, v/v) extract of the incubation mixture. Some of the fundamental factors involved in the procedure are discussed.", "contents": "Tributyrate as a substrate for the determination of lipase activity in milk. A procedure is described for the determination of the lipolytic activity in milk using tributyrate as substrate. The method is based on the titration of liberated butyric acid in a diethyl ether: light petroleum (2-75:1, v/v) extract of the incubation mixture. Some of the fundamental factors involved in the procedure are discussed."}
{"id": "PMID:237941", "title": "Lipases in bovine milk and the relationship between the lipoprotein lipase and tributyrate hydrolysing activities in cream and skim-milk.", "content": "The lipoprotein lipase and tributyrate hydrolysing activities were found to be similarly distributed in the fractions obtained when whole milk was separated into skim-milk and cream, and when the cream was washed and freed from lipid. These enzyme activities in skim-milks and in extracts of lipid-free cream could not be separated by affinity chromatography on heparin-Sepharose. The enzymes were inactivated to the same degree when incubated at 37 degrees C in the presence of 1-5 M-NaCl, pH 8-5,  and both showed marked decrease in stability at 4 degrees C in UV-light caused the same decrease in both lipoprotein lipase and tributyrate hydrolysing activities. An antiserum against a highly purified skim-milk lipoprotein lipase caused total inhibition of the lipoprotein lipase and tributyrate hydrolysing activities in skim-milk and in extracts of lipid-free cream. It is suggested that in bovine milk there is only one major lipase and that it is identical to lipoprotein lipase.", "contents": "Lipases in bovine milk and the relationship between the lipoprotein lipase and tributyrate hydrolysing activities in cream and skim-milk. The lipoprotein lipase and tributyrate hydrolysing activities were found to be similarly distributed in the fractions obtained when whole milk was separated into skim-milk and cream, and when the cream was washed and freed from lipid. These enzyme activities in skim-milks and in extracts of lipid-free cream could not be separated by affinity chromatography on heparin-Sepharose. The enzymes were inactivated to the same degree when incubated at 37 degrees C in the presence of 1-5 M-NaCl, pH 8-5,  and both showed marked decrease in stability at 4 degrees C in UV-light caused the same decrease in both lipoprotein lipase and tributyrate hydrolysing activities. An antiserum against a highly purified skim-milk lipoprotein lipase caused total inhibition of the lipoprotein lipase and tributyrate hydrolysing activities in skim-milk and in extracts of lipid-free cream. It is suggested that in bovine milk there is only one major lipase and that it is identical to lipoprotein lipase."}
{"id": "PMID:237942", "title": "The precipitation of proteins by carboxymethyl cellulose.", "content": "Carboxymethyl cellulose (CMC) formed insoluble complexes with beta-lactoglobulin, bovine serum albumin and Na caseinate. Maximum precipitation of the beta-lactoglobulin-CMC complex occurred at pH 3-2, whereas maximum precipitation of the bovine serum albumin. The percentage of protein precipitated by CMC decreased with increasing ionic strength of the solution, the rate of decrease being least for bovine serum albumin. At a given ionic strength, more protein was precipitated by CMC of high degree of substitution than by CMC of low degree of substitution. The change in pH (delta pH) occurring on mixing CMC and unbuffered protein solutions, each initially at the same pH, was measured. delta pH was negative for beta-lactoglobulin-CMC mixtures over the pH range 7--2 (minimum at pH 5-5). For bovine serum albumin--Cmc and Na caseinate--CMC mixtures, delta pH was positive between pH 7 and 3-2 (maximum at pH 4-5), zero at pH 3-2 and negative between pH 3-2 and 2-0 (minimum at pH 2-8).", "contents": "The precipitation of proteins by carboxymethyl cellulose. Carboxymethyl cellulose (CMC) formed insoluble complexes with beta-lactoglobulin, bovine serum albumin and Na caseinate. Maximum precipitation of the beta-lactoglobulin-CMC complex occurred at pH 3-2, whereas maximum precipitation of the bovine serum albumin. The percentage of protein precipitated by CMC decreased with increasing ionic strength of the solution, the rate of decrease being least for bovine serum albumin. At a given ionic strength, more protein was precipitated by CMC of high degree of substitution than by CMC of low degree of substitution. The change in pH (delta pH) occurring on mixing CMC and unbuffered protein solutions, each initially at the same pH, was measured. delta pH was negative for beta-lactoglobulin-CMC mixtures over the pH range 7--2 (minimum at pH 5-5). For bovine serum albumin--Cmc and Na caseinate--CMC mixtures, delta pH was positive between pH 7 and 3-2 (maximum at pH 4-5), zero at pH 3-2 and negative between pH 3-2 and 2-0 (minimum at pH 2-8)."}
{"id": "PMID:237943", "title": "Acid phosphatases activity in cheese and starters.", "content": "The acid phosphatase activity levels in a number of Greek cheeses and in Cheddar cheeses were found to be unaffected by storage for up to 18 months and 12 months respectively. In Cheddar cheese, starter organisms made an insignificant contribution to this activity. Studies of acid phosphatase prepared from Streptococcus cremoris-lactis NCDO 762 starter cultures showed that the enzyme was of high molecular weight and largely particle-bound. The pH of optimum activity was 5-2 and the enzyme was inhibited by F-minus,Al-3+, a number of heavy metals, oxidizing agents and sulphydryl-modifying reagents. Kinetic measurements at pH 5-2 gave a Km value for p-nitrophenyl phosphate of 1-2 mM. Orthophosphate, pyrophosphate and isoelectrically precipitated casein behaved as competitive inhibitors to the hydrolysis of p-nitrophenyl phosphate with Ki values of 1-2 mM, 1-0 mM, 1-0 MM and 1-1 mM respectively. In spite of this binding to the enzyme, casein provided a very poor substrate for the starter acid phosphatase. The properties of acid phosphatase present in Cheddar cheese made with Str. cremoris NCDO 924 starter were consistent with the enzyme being exclusively of milk origin and small differences between this and the acid phosphatase previously isolated from bovine milk were attributable to the binding of peptides produced during the cheese maturation to the enzyme molecules. It was concluded that in cheese, phosphatase action was due largely to the enzyme of milk origin, with that provided by the starter being of minor importance.", "contents": "Acid phosphatases activity in cheese and starters. The acid phosphatase activity levels in a number of Greek cheeses and in Cheddar cheeses were found to be unaffected by storage for up to 18 months and 12 months respectively. In Cheddar cheese, starter organisms made an insignificant contribution to this activity. Studies of acid phosphatase prepared from Streptococcus cremoris-lactis NCDO 762 starter cultures showed that the enzyme was of high molecular weight and largely particle-bound. The pH of optimum activity was 5-2 and the enzyme was inhibited by F-minus,Al-3+, a number of heavy metals, oxidizing agents and sulphydryl-modifying reagents. Kinetic measurements at pH 5-2 gave a Km value for p-nitrophenyl phosphate of 1-2 mM. Orthophosphate, pyrophosphate and isoelectrically precipitated casein behaved as competitive inhibitors to the hydrolysis of p-nitrophenyl phosphate with Ki values of 1-2 mM, 1-0 mM, 1-0 MM and 1-1 mM respectively. In spite of this binding to the enzyme, casein provided a very poor substrate for the starter acid phosphatase. The properties of acid phosphatase present in Cheddar cheese made with Str. cremoris NCDO 924 starter were consistent with the enzyme being exclusively of milk origin and small differences between this and the acid phosphatase previously isolated from bovine milk were attributable to the binding of peptides produced during the cheese maturation to the enzyme molecules. It was concluded that in cheese, phosphatase action was due largely to the enzyme of milk origin, with that provided by the starter being of minor importance."}
{"id": "PMID:237944", "title": "Electrophoresis of cottage cheese whey proteins and their polymers.", "content": "Cottage cheese whey solutions containing sodium dodecyl sulfate were resolved electrophoretically on 5% sodium dodecyl sulfate polyacrylamide gels. Major bands were identified by comparing their electrophoretic mobilities to those of known whey components. Other components were identified principally from molecular weights determined from a calibration correlating mobility and molecular weight. Conditions which affect polymerization of proteins were studied in whey and solutions of purified beta-lactoglobulin. Formation of a number of polymers was induced by concentrating the whey samples, lowering the temperature, adjusting pH, or adding salts. The dimer, trimer, tetramer, and octamer of beta-lactoglobulin, the dimer and trimer of bovine serum albumin, and several unidentified components in the 100,000 to 300,000 molecular weight range were observed. The octamer state of beta-lactoglobulin was observed in whey at pH values between 5.1 and 8.0, at temperatures below 10 C, and with .2M addition of potassium thiocyanate, potassium iodide, calcium chloride, or sodium acetate. Similar polymer formation, and temperature and pH effects, were observed with solutions of purified beta-lactoglobulin, which contained dimers, trimers, and tetramers. The beta-lactoglobulin octamer in whey samples could be dissociated by the addition of acid. The bovine serum albumin dimer appeared in whey at pH above 6.2 and at -minus 1 C.", "contents": "Electrophoresis of cottage cheese whey proteins and their polymers. Cottage cheese whey solutions containing sodium dodecyl sulfate were resolved electrophoretically on 5% sodium dodecyl sulfate polyacrylamide gels. Major bands were identified by comparing their electrophoretic mobilities to those of known whey components. Other components were identified principally from molecular weights determined from a calibration correlating mobility and molecular weight. Conditions which affect polymerization of proteins were studied in whey and solutions of purified beta-lactoglobulin. Formation of a number of polymers was induced by concentrating the whey samples, lowering the temperature, adjusting pH, or adding salts. The dimer, trimer, tetramer, and octamer of beta-lactoglobulin, the dimer and trimer of bovine serum albumin, and several unidentified components in the 100,000 to 300,000 molecular weight range were observed. The octamer state of beta-lactoglobulin was observed in whey at pH values between 5.1 and 8.0, at temperatures below 10 C, and with .2M addition of potassium thiocyanate, potassium iodide, calcium chloride, or sodium acetate. Similar polymer formation, and temperature and pH effects, were observed with solutions of purified beta-lactoglobulin, which contained dimers, trimers, and tetramers. The beta-lactoglobulin octamer in whey samples could be dissociated by the addition of acid. The bovine serum albumin dimer appeared in whey at pH above 6.2 and at -minus 1 C."}
{"id": "PMID:237945", "title": "Heat resistant proteases produced in milk by psychrotrophic bacteria of dairy origin.", "content": "Production of heat resistant proteases by psychrotrophs growing in milk, resistance of such proteases to ultrahigh temperature treatments and action of these enzymes on milk were studied. All of the psychrotrophs obtained from raw milk produced proteases that survived 149 C for 10s. Seventy to ninety percent of the raw milk samples contained psychrotrophs capable of producing heat resistant proteases. The protease chosen as a model was resistant to heat treatments at 110 to 150 C, and the inactivation parameters suggested that thermal destruction of heat resistant proteases would damage the milk severely. The casein content and pH of normal milk were suitable for protease action, and the protease was quite active at normal and elevated room temperatures. The protease rapidly spoiled sterile milk with the development of bitter flavor, clearing, or coagulation; and the susceptibility of sterile milk to protease increased during storage of the milk.", "contents": "Heat resistant proteases produced in milk by psychrotrophic bacteria of dairy origin. Production of heat resistant proteases by psychrotrophs growing in milk, resistance of such proteases to ultrahigh temperature treatments and action of these enzymes on milk were studied. All of the psychrotrophs obtained from raw milk produced proteases that survived 149 C for 10s. Seventy to ninety percent of the raw milk samples contained psychrotrophs capable of producing heat resistant proteases. The protease chosen as a model was resistant to heat treatments at 110 to 150 C, and the inactivation parameters suggested that thermal destruction of heat resistant proteases would damage the milk severely. The casein content and pH of normal milk were suitable for protease action, and the protease was quite active at normal and elevated room temperatures. The protease rapidly spoiled sterile milk with the development of bitter flavor, clearing, or coagulation; and the susceptibility of sterile milk to protease increased during storage of the milk."}
{"id": "PMID:237946", "title": "Heat stability and reactivation of mare milk lysozyme.", "content": "Mare milk and aqueous solution of mare milk lysozyme were incubated for variable times between 30 C and 100 C at pH 3, 6, or 9. Lysozyme activity was stable at acid and neutral pH and labile at alkaline pH. Some of the results show the existence of a reactivation process in mare's milk and in aqueous solution. reaching 30 to 40% after incubation of the aqueous solution at 4 C for 20 days at pH 3 or 6.", "contents": "Heat stability and reactivation of mare milk lysozyme. Mare milk and aqueous solution of mare milk lysozyme were incubated for variable times between 30 C and 100 C at pH 3, 6, or 9. Lysozyme activity was stable at acid and neutral pH and labile at alkaline pH. Some of the results show the existence of a reactivation process in mare's milk and in aqueous solution. reaching 30 to 40% after incubation of the aqueous solution at 4 C for 20 days at pH 3 or 6."}
{"id": "PMID:237947", "title": "Chemistry of milk proteins in food processing.", "content": "This paper analyzes the current knowledge of mild protein chemistry to explain the reactions and their control for the major processes utilized by the modern milk processing industry. The compositon and chemical properties of casein micelles and whey proteins are summarized. The effect of processing upon denaturation, aggregration, and destabilization of milk proteins is updated. The role of milk proteins in the gelation of sterile milk concentrates, destabilization of frozen milk, rennet-clotting of milk, and stabilization of the fat emulsion in milk is also described.", "contents": "Chemistry of milk proteins in food processing. This paper analyzes the current knowledge of mild protein chemistry to explain the reactions and their control for the major processes utilized by the modern milk processing industry. The compositon and chemical properties of casein micelles and whey proteins are summarized. The effect of processing upon denaturation, aggregration, and destabilization of milk proteins is updated. The role of milk proteins in the gelation of sterile milk concentrates, destabilization of frozen milk, rennet-clotting of milk, and stabilization of the fat emulsion in milk is also described."}
{"id": "PMID:237948", "title": "Enamel demineralization by snack foods.", "content": "The amount of enamel destroyed by salivary fermentation of snack foods and confections was not dependent on their sugar content; starch, flavoring agents, and other components also played a part. Most enamel destruction was produced by fruit-flavored candies in which the inherent acid or high sugar concentration or both inhibited bacterial fermentation.", "contents": "Enamel demineralization by snack foods. The amount of enamel destroyed by salivary fermentation of snack foods and confections was not dependent on their sugar content; starch, flavoring agents, and other components also played a part. Most enamel destruction was produced by fruit-flavored candies in which the inherent acid or high sugar concentration or both inhibited bacterial fermentation."}
{"id": "PMID:237949", "title": "Formation of Ca HPO4-2H2O from enamel mineral and its relationship to caries mechanism.", "content": "Tooth enamel, when treated with dilute H3P94 solutions, dissolved incongruently with formation of large CaHPO4-2HO2O crystals. Equilibrated solutions were saturated with respect to Ca5(PO4)3OH, probably an impure, defective apatite. The CaHPO4-2H2O crystals formed at considerably higher pH values than expected becuase of enhanced solubility of the apatitic phase in enamel. Pyolysis of carious enamel revealed the presence of acidic calcium phosphate presumed to be CaHPO4-2H2O.", "contents": "Formation of Ca HPO4-2H2O from enamel mineral and its relationship to caries mechanism. Tooth enamel, when treated with dilute H3P94 solutions, dissolved incongruently with formation of large CaHPO4-2HO2O crystals. Equilibrated solutions were saturated with respect to Ca5(PO4)3OH, probably an impure, defective apatite. The CaHPO4-2H2O crystals formed at considerably higher pH values than expected becuase of enhanced solubility of the apatitic phase in enamel. Pyolysis of carious enamel revealed the presence of acidic calcium phosphate presumed to be CaHPO4-2H2O."}
{"id": "PMID:237954", "title": "The physician's assistant.", "content": "A physician's assistant is trained to act in the place of the physician in the diagnostic and therapeutic management of patients. Tasks that can be performed by assistants, legislation related to their responsibilities, the question of physician supervision, educational programs and certification, and factors in employment are matters that are being dealt with by our colleagues in medicine. The acceptance of this new category of health care personnel has implications for the status of expanded duty dental auxiliaries in dentistry.", "contents": "The physician's assistant. A physician's assistant is trained to act in the place of the physician in the diagnostic and therapeutic management of patients. Tasks that can be performed by assistants, legislation related to their responsibilities, the question of physician supervision, educational programs and certification, and factors in employment are matters that are being dealt with by our colleagues in medicine. The acceptance of this new category of health care personnel has implications for the status of expanded duty dental auxiliaries in dentistry."}
{"id": "PMID:237957", "title": "Observations on the psychopharmacology of the aged.", "content": "Psychotropic drugs are discussed under the descriptive categories of antipsychotic, antidepressive, antimanic, anti-anxiety, and cognitive acting. In the antipsychotic classification, special attention is given to side effects (extrapyramidal motor signs, tardive dyskinesias, akathisis) and to dosage for the elderly. The section on congenitive acting drugs includes some pertinent observations on cognitive ability in the aging, the importance of correct diagnosis, and therapeutic strategy. The aged are a population at risk for not only disease, but iatrongenic illness due to direct and indirect drug action. Rational therapy involves understanding the underlying dynamics of the disease and thus the selection of the most effective treatment. Psychotropic drugs in an appropriate program are valuable therapeutic assets.", "contents": "Observations on the psychopharmacology of the aged. Psychotropic drugs are discussed under the descriptive categories of antipsychotic, antidepressive, antimanic, anti-anxiety, and cognitive acting. In the antipsychotic classification, special attention is given to side effects (extrapyramidal motor signs, tardive dyskinesias, akathisis) and to dosage for the elderly. The section on congenitive acting drugs includes some pertinent observations on cognitive ability in the aging, the importance of correct diagnosis, and therapeutic strategy. The aged are a population at risk for not only disease, but iatrongenic illness due to direct and indirect drug action. Rational therapy involves understanding the underlying dynamics of the disease and thus the selection of the most effective treatment. Psychotropic drugs in an appropriate program are valuable therapeutic assets."}
{"id": "PMID:237958", "title": "A survey of the prescribing and administration of drugs in a long-term care institution for the elderly.", "content": "The prescription and administration of drugs (especially of the neuroactive class) was observed in 131 patients in an extended care facility. The average number of neuroactive drugs prescribed (2.1) was distinctly different from the average number administered (1.3) because of the large number of pro re nata (prn) prescriptions. More neuroactive substances were prescribed for patients with superior mentation and minimal physical disability; the difference between low and high groups was 1.7 (mentation) and 2.8 (physical status). The most common neuroactive drugs prescribed were: 1) analgesics, 2) major tranquilizers, and 3) hypnotics. Questionable prescribing practices were demonstrated by the fact that 30 patients had prescriptions for 38 \"not-recommended\"drugs; 23 of these prescriptions were for propoxyphene compound. After requiring physicians to rewrite drug orders every thirty days, a survey made ten months later showed that there was a decline (0.8) in the number of drugs prescribed per patient and a slight increase (0.45) in the number of drugs administered. Professional drug surveillance is crucial for improving the therapeutic process. At least two modifications of current prescribing practices are recommended: 1) a record should always be made of the precise condition(s) under which a drug prescribed \"prn\" is to be administered; and 2) a strong effort should be made to reduce the total number of drug prescriptions. The results of this survey suggest that certain procedural matters necessitating change are not in themselves the most substantive factors in improvement. Present \"third party\" review mechanisms likely will not ameliorate the current situation. It will be necessary to implement complex organizational changes in most extended care facilities.", "contents": "A survey of the prescribing and administration of drugs in a long-term care institution for the elderly. The prescription and administration of drugs (especially of the neuroactive class) was observed in 131 patients in an extended care facility. The average number of neuroactive drugs prescribed (2.1) was distinctly different from the average number administered (1.3) because of the large number of pro re nata (prn) prescriptions. More neuroactive substances were prescribed for patients with superior mentation and minimal physical disability; the difference between low and high groups was 1.7 (mentation) and 2.8 (physical status). The most common neuroactive drugs prescribed were: 1) analgesics, 2) major tranquilizers, and 3) hypnotics. Questionable prescribing practices were demonstrated by the fact that 30 patients had prescriptions for 38 \"not-recommended\"drugs; 23 of these prescriptions were for propoxyphene compound. After requiring physicians to rewrite drug orders every thirty days, a survey made ten months later showed that there was a decline (0.8) in the number of drugs prescribed per patient and a slight increase (0.45) in the number of drugs administered. Professional drug surveillance is crucial for improving the therapeutic process. At least two modifications of current prescribing practices are recommended: 1) a record should always be made of the precise condition(s) under which a drug prescribed \"prn\" is to be administered; and 2) a strong effort should be made to reduce the total number of drug prescriptions. The results of this survey suggest that certain procedural matters necessitating change are not in themselves the most substantive factors in improvement. Present \"third party\" review mechanisms likely will not ameliorate the current situation. It will be necessary to implement complex organizational changes in most extended care facilities."}
{"id": "PMID:237963", "title": "Human epidermal transamidase.", "content": "The possible presence of epsilon-(gamma-glutamyl) lysine covalent bonds in human epidermal proteins prompted a study of transamidase activity in human hair-free epidermis. Callus contains an enzyme which catalyzes the incorporation of radioactive putrescine into alpha-casein. The enzyme is active without prior treatment with exogenous proteolytic enzymes. The putrescine incorporation is calcium dependent and inhibited by iodoacetamide. The enzyme was partially purified (50-fold over starting material), and has an apparent molecular weight between 50,000 daltons and 55,000 daltons by agarose 0.5m gel filtration. The apparent molecular weight is unaltered by chromatography in the presence of 11 mMCaCl2, a condition known to dissociate plasma transglutaminase (Factor XIII) into its ultimate subunits. The enzyme is active over a wide pH range up to pH 10.4 The Km for putrescine varies by 1-fold over the pH range 6.0 to 10.2, although enzyme activity increases at least 20-fold over the same pH range. The human epidermal transamidase is similar to the guinea-pig hair follicle transglutaminase and cow snout transamidase in its ability to cross-link fibrin.", "contents": "Human epidermal transamidase. The possible presence of epsilon-(gamma-glutamyl) lysine covalent bonds in human epidermal proteins prompted a study of transamidase activity in human hair-free epidermis. Callus contains an enzyme which catalyzes the incorporation of radioactive putrescine into alpha-casein. The enzyme is active without prior treatment with exogenous proteolytic enzymes. The putrescine incorporation is calcium dependent and inhibited by iodoacetamide. The enzyme was partially purified (50-fold over starting material), and has an apparent molecular weight between 50,000 daltons and 55,000 daltons by agarose 0.5m gel filtration. The apparent molecular weight is unaltered by chromatography in the presence of 11 mMCaCl2, a condition known to dissociate plasma transglutaminase (Factor XIII) into its ultimate subunits. The enzyme is active over a wide pH range up to pH 10.4 The Km for putrescine varies by 1-fold over the pH range 6.0 to 10.2, although enzyme activity increases at least 20-fold over the same pH range. The human epidermal transamidase is similar to the guinea-pig hair follicle transglutaminase and cow snout transamidase in its ability to cross-link fibrin."}
{"id": "PMID:237964", "title": "Cyclic 3',5'-nucleotide phosphodiesterase in rat skin. II. Biochemical characterization.", "content": "The biochemical characteristics of cyclic 3',5'-nucleotide phosphodiesterase were studied in homogenates of male albino rat skin using preparations which were predominantly epidermal. Enzymatic activity was detected in both the particulate and soluble fractions of these skin homogenates. Two kinetically distinct phosphodiesterase (PDE) activities were detected in the soluble fraction (100,000 times g supernatant). This 100,000 times g supernatant contains at least two distinct protein bands that hydrolyze cyclic AMP as demonstrated by gel electrophoresis. Divalent cations (Mg-++ or Mn-++) and 2-mercaptoethanol were required for maximal enzymatic activity. Epinephrine, dibutyryl cyclic AMP, and methylxanthines inhibited while imidazole and histamine phosphate stimulated the cyclic AMP phosphodiesterase activity at high and low cyclic AMP concentrations. Cyclic GMP competitively inhibited hydrolysis of low, but not high, concentrations of cyclic AMP. Hydrocortisone phosphate in pharmacologic concentrations blocked PDE denaturation by heat. These studies indicate that there are complex interrelationships between cyclic nucleotides and PDE in rat skin.", "contents": "Cyclic 3',5'-nucleotide phosphodiesterase in rat skin. II. Biochemical characterization. The biochemical characteristics of cyclic 3',5'-nucleotide phosphodiesterase were studied in homogenates of male albino rat skin using preparations which were predominantly epidermal. Enzymatic activity was detected in both the particulate and soluble fractions of these skin homogenates. Two kinetically distinct phosphodiesterase (PDE) activities were detected in the soluble fraction (100,000 times g supernatant). This 100,000 times g supernatant contains at least two distinct protein bands that hydrolyze cyclic AMP as demonstrated by gel electrophoresis. Divalent cations (Mg-++ or Mn-++) and 2-mercaptoethanol were required for maximal enzymatic activity. Epinephrine, dibutyryl cyclic AMP, and methylxanthines inhibited while imidazole and histamine phosphate stimulated the cyclic AMP phosphodiesterase activity at high and low cyclic AMP concentrations. Cyclic GMP competitively inhibited hydrolysis of low, but not high, concentrations of cyclic AMP. Hydrocortisone phosphate in pharmacologic concentrations blocked PDE denaturation by heat. These studies indicate that there are complex interrelationships between cyclic nucleotides and PDE in rat skin."}
{"id": "PMID:237965", "title": "Quantitative microbiology of the scalp in non-dandruff, dandruff, and seborrheic dermatitis.", "content": "The composition of the scalp microflora was assessed quantitatively in normal individuals and in patients with dandruff and seborrheic dermatitis, disorders characterized by increasing scaling. Three organisms were constantly found: (1) Pityrosporum, (2) aerobic cocci, and (3) Corynebacterium acnes. Pityrosporum (mainly Pityrosporum ovale) made up 46% of the total microflora in normals, 74% in dandruff, and 83% in seborvheic dermatitis. The geometric mean number of organisms per cm-2 in non-dandruff subjects was 5.04 times 10-5; 9.22 times 10-5 in dandruff subjects; and 6.45 times 10-5 in those with seborrheic dermatitis. The cocci were dominantly Baird-Parker type SII and no quantitative or qualitative change occurred in the scaling disorders. C. acnes comprised 26% of the flora on the normal scalp, 6% in dandruff, and only 1% in seborrheic dermatitis. These results differ significantly from previous reports which describe a much more complex microflora and suggest an etiologic role for microorganisms in dandruff.", "contents": "Quantitative microbiology of the scalp in non-dandruff, dandruff, and seborrheic dermatitis. The composition of the scalp microflora was assessed quantitatively in normal individuals and in patients with dandruff and seborrheic dermatitis, disorders characterized by increasing scaling. Three organisms were constantly found: (1) Pityrosporum, (2) aerobic cocci, and (3) Corynebacterium acnes. Pityrosporum (mainly Pityrosporum ovale) made up 46% of the total microflora in normals, 74% in dandruff, and 83% in seborvheic dermatitis. The geometric mean number of organisms per cm-2 in non-dandruff subjects was 5.04 times 10-5; 9.22 times 10-5 in dandruff subjects; and 6.45 times 10-5 in those with seborrheic dermatitis. The cocci were dominantly Baird-Parker type SII and no quantitative or qualitative change occurred in the scaling disorders. C. acnes comprised 26% of the flora on the normal scalp, 6% in dandruff, and only 1% in seborrheic dermatitis. These results differ significantly from previous reports which describe a much more complex microflora and suggest an etiologic role for microorganisms in dandruff."}
{"id": "PMID:237966", "title": "Analysis of lipid composition of isolated human sebaceous gland homogenates after incubation with cutaneous bacteria. Thin-layer chromatography.", "content": "The effects of specific species of skin bacteria on human sebaceous gland lipids in vitro were analyzed. Isolated dissected sebaceous glands were pooled, homogenized, and sterilized, then incorporated into peptone-yeast extract medium and used as substrate for growth of Propionibacterium acnes, P. granulosum, and Staphylococcus epidermidis subgroup II. The sebaceous lipids were analyzed by thin-layer chromatography before and after bacterial growth. The most striking effect of bacteria on sebaceous gland lipid composition was the hydrolysis of sebaceous triglycerides. The degree of hydrolysis varied with bacterial strain but was most complete with P. acnes and P. granulosum. Staphylococci were not effective in hydrolyzing sebaceous triglycerides at pH 4.5 although, when the pH of the medium was raised to pH 6.4, some strains of staphylococci were as effective as the propionibacteria in hydrolyzing sebaceous triglycerides to free fatty acids. Thus minor changes in acidity may play asignificant role in controlling the lipolytic activity of staphylococci on skin. Another effect of bacterial action on sebaceous gland lipids was the esterification of sebaceous cholesterol to cholesteryl esters. Thus, bacterial action must be taken into account in evaluating studies of alterations in cutaneous cholesterol and cholesteryl esters in skin surface lipids in normal and disease states.", "contents": "Analysis of lipid composition of isolated human sebaceous gland homogenates after incubation with cutaneous bacteria. Thin-layer chromatography. The effects of specific species of skin bacteria on human sebaceous gland lipids in vitro were analyzed. Isolated dissected sebaceous glands were pooled, homogenized, and sterilized, then incorporated into peptone-yeast extract medium and used as substrate for growth of Propionibacterium acnes, P. granulosum, and Staphylococcus epidermidis subgroup II. The sebaceous lipids were analyzed by thin-layer chromatography before and after bacterial growth. The most striking effect of bacteria on sebaceous gland lipid composition was the hydrolysis of sebaceous triglycerides. The degree of hydrolysis varied with bacterial strain but was most complete with P. acnes and P. granulosum. Staphylococci were not effective in hydrolyzing sebaceous triglycerides at pH 4.5 although, when the pH of the medium was raised to pH 6.4, some strains of staphylococci were as effective as the propionibacteria in hydrolyzing sebaceous triglycerides to free fatty acids. Thus minor changes in acidity may play asignificant role in controlling the lipolytic activity of staphylococci on skin. Another effect of bacterial action on sebaceous gland lipids was the esterification of sebaceous cholesterol to cholesteryl esters. Thus, bacterial action must be taken into account in evaluating studies of alterations in cutaneous cholesterol and cholesteryl esters in skin surface lipids in normal and disease states."}
{"id": "PMID:237967", "title": "Human necrotizing vasculitis: immunoglobulins and complement in vessel walls of cutaneous lesions and normal skin.", "content": "Immunoglobulins and C3 were detected by immunofluorescence in the blood vessel walls of biopsies of clinically normal skin in patients with active necrotizing vasculitis. Of the 13 patients studied, 9 had C3 and 6 of these had IgM or IgA in biopsies of lesions of vasculitis. In adjacent clinically normal skin, 7 patients had C3 and 3 of these also had IgM or IgA. These findings support the hypothesis that immunoglobulins and complement are present in vessels of some patients prior to chemotaxis of polymorphonuclear leukocytes and the resulting inflammatory purpuric lesions so characteristic of necrotizing vasculitis.", "contents": "Human necrotizing vasculitis: immunoglobulins and complement in vessel walls of cutaneous lesions and normal skin. Immunoglobulins and C3 were detected by immunofluorescence in the blood vessel walls of biopsies of clinically normal skin in patients with active necrotizing vasculitis. Of the 13 patients studied, 9 had C3 and 6 of these had IgM or IgA in biopsies of lesions of vasculitis. In adjacent clinically normal skin, 7 patients had C3 and 3 of these also had IgM or IgA. These findings support the hypothesis that immunoglobulins and complement are present in vessels of some patients prior to chemotaxis of polymorphonuclear leukocytes and the resulting inflammatory purpuric lesions so characteristic of necrotizing vasculitis."}
{"id": "PMID:237970", "title": "In vivo hepatic and intestinal toxicity of sodium cyanate in rats: cyanate-induced alterations in hepatic glycogen metabolism.", "content": "To determine the hepatic and intestinal toxicity of sodium cyanate, this compound was administered to rats by orogastric tube (PO) or intraperitoneal injection (IP). At low dosage (50 mg. per kilogram per day PO for 8 weeks), the animals showed no clinical effects other than mild lethargy. They had normal intestinal absorption studies, but demonstrated decreased liver G6PD activity and a slight increase in hepatic glycogen. At higher dose levels (200 mg. per kilogram per day PO for 10 days, 400 mg. per kilogram per day PO for 3 days, and 100 mg. per kilogram per day IP for 10 days), the animals became very lethargic and developed hind-limb paralysis; many animals died during the period of dosing. The severity and rate of onset of symptoms increased proportionally with the dose level. Liver sections from rats receiving these higher doses showed striking increases in glycogen deposition. Activities of hepatic enzymes involved in glycogen synthesis and degradation were measured in rats receiving 200 mg. per kilogram per day PO  or 100 mg. per kilogram per day IP. Significant decreases were noted in the activities of glucose-6-phosphatase and G6PD in PO-dosed rats. The activities of phosphorylase, UDPG-pyrophosphorylase, glycogen synthetase, phosphoglucomutase, and debrancher did not differ from control rats. In IP-dosed rats, significant decreases were observed in the activities of glucose-6-phosphatase, G6PD, phosphorylase, and UDPG-pyrophosphorylase, but not in the other glycogen-related enzymes. Our data suggest that sodium cyanate affects several enzymes of hepatic glycogen metabolism but that the enzymes vary in their susceptibility (glucose-6-phosphatase and G6PD greater than phosphorylase and UDPG pyrophosphorylase.", "contents": "In vivo hepatic and intestinal toxicity of sodium cyanate in rats: cyanate-induced alterations in hepatic glycogen metabolism. To determine the hepatic and intestinal toxicity of sodium cyanate, this compound was administered to rats by orogastric tube (PO) or intraperitoneal injection (IP). At low dosage (50 mg. per kilogram per day PO for 8 weeks), the animals showed no clinical effects other than mild lethargy. They had normal intestinal absorption studies, but demonstrated decreased liver G6PD activity and a slight increase in hepatic glycogen. At higher dose levels (200 mg. per kilogram per day PO for 10 days, 400 mg. per kilogram per day PO for 3 days, and 100 mg. per kilogram per day IP for 10 days), the animals became very lethargic and developed hind-limb paralysis; many animals died during the period of dosing. The severity and rate of onset of symptoms increased proportionally with the dose level. Liver sections from rats receiving these higher doses showed striking increases in glycogen deposition. Activities of hepatic enzymes involved in glycogen synthesis and degradation were measured in rats receiving 200 mg. per kilogram per day PO  or 100 mg. per kilogram per day IP. Significant decreases were noted in the activities of glucose-6-phosphatase and G6PD in PO-dosed rats. The activities of phosphorylase, UDPG-pyrophosphorylase, glycogen synthetase, phosphoglucomutase, and debrancher did not differ from control rats. In IP-dosed rats, significant decreases were observed in the activities of glucose-6-phosphatase, G6PD, phosphorylase, and UDPG-pyrophosphorylase, but not in the other glycogen-related enzymes. Our data suggest that sodium cyanate affects several enzymes of hepatic glycogen metabolism but that the enzymes vary in their susceptibility (glucose-6-phosphatase and G6PD greater than phosphorylase and UDPG pyrophosphorylase."}
{"id": "PMID:237972", "title": "Catecholamine content of serum and adrenals in protracted anaphylactic shock of guinea pigs.", "content": "In ovalbumin-sensitized guinea pigs, the serum catecholamines were significantly increased 20 or 120 min after antigen injection. The highest serum cathecholamine values were obtained in animals which were selected during a severe state of protracted shock, and in those which died in protracted shock. Antihistamine pretreatment reduced the serum noradrenaline, but not the adrenaline values in anaphylaxis. In urethane anesthesia, the anaphylactic serum catecholamine levels (especially noradrenaline) were lower than in nonanesthetized animals. The adrenaline and noradrenaline content of the adrenals in protracted and in acute anaphylactic shock did not differ from control values.", "contents": "Catecholamine content of serum and adrenals in protracted anaphylactic shock of guinea pigs. In ovalbumin-sensitized guinea pigs, the serum catecholamines were significantly increased 20 or 120 min after antigen injection. The highest serum cathecholamine values were obtained in animals which were selected during a severe state of protracted shock, and in those which died in protracted shock. Antihistamine pretreatment reduced the serum noradrenaline, but not the adrenaline values in anaphylaxis. In urethane anesthesia, the anaphylactic serum catecholamine levels (especially noradrenaline) were lower than in nonanesthetized animals. The adrenaline and noradrenaline content of the adrenals in protracted and in acute anaphylactic shock did not differ from control values."}
{"id": "PMID:237973", "title": "Release of corticotrophin releasing factor and other hypophysiotropic substances from isolated nerve-endings (synaptosomes).", "content": "Synaptosomes isolated from the sheep and the rat hypothalamus contain corticotrophin releasing factor, vasopressin, prolactin-release inhibiting factor and probably all of the substances which participate in the regulation of adenohypophysial function. Electrical field stimulation or depolarizing concentrations (55 mmol/l) of potassium ions cause a release of these factors from the incubated nerve-endings in a calcium-dependent manner. It is suggested that synaptosomes may provide a valuable approach to the study of mechanisms involved in hypothalamic neurosecretion in vitro.", "contents": "Release of corticotrophin releasing factor and other hypophysiotropic substances from isolated nerve-endings (synaptosomes). Synaptosomes isolated from the sheep and the rat hypothalamus contain corticotrophin releasing factor, vasopressin, prolactin-release inhibiting factor and probably all of the substances which participate in the regulation of adenohypophysial function. Electrical field stimulation or depolarizing concentrations (55 mmol/l) of potassium ions cause a release of these factors from the incubated nerve-endings in a calcium-dependent manner. It is suggested that synaptosomes may provide a valuable approach to the study of mechanisms involved in hypothalamic neurosecretion in vitro."}
{"id": "PMID:237974", "title": "Phosphatase active antigens in sea urchin eggs and embryos. I. Substrate specificity, pH-optima and inhibitors.", "content": "Phosphatase activity in sea urchin embryonic antigens was investigated by histochemical staining of immunoprecipitates separated by two-dimensional (crossed) immunoelectrophoresis. Unfertilized eggs were homogenized in a hypotonic medium which solubilized cytoplasmic antigens. Antigens integrated in membranes or enclosed in particles were solubilized by detergent treatment of the residual pellet. Two different phosphatase activities were discerned in the unfertilized eggs, nucleoside diphosphatase (EC 3.6.1.6.) and acid phosphatase (EC 3.1.3.2.). Nucleoside diphosphatase activity was obtained in both the water soluble and detergent extracted protein fractions. This activity was confined to one antigen. Acid phosphatase acitivity on the other hand was almost exclusively obtained in the detergent extracted fraction and about ten distinct antigens displayed this activity. The nucleoside diphosphatase active antigen preferentially hydrolyzed purine nucleoside diphosphates and to a lesser degree triphosphates of these nucleosides. The acid phosphatase active antigens had a broader substrate specificity and hydrolyzed equally well beta-glycerophosphate and nucleotides. Both activities were essentially inactive at neutral or alkaline pH values. The activities were inhibited by p-choloromercuribenzoate and accordingly stimulated by cysteine. Tartrate and sodium fluoride, however, inhibited the acid phosphatase activity while nucleoside diphosphatase activity was either stimulated or not affected at all by these agents.", "contents": "Phosphatase active antigens in sea urchin eggs and embryos. I. Substrate specificity, pH-optima and inhibitors. Phosphatase activity in sea urchin embryonic antigens was investigated by histochemical staining of immunoprecipitates separated by two-dimensional (crossed) immunoelectrophoresis. Unfertilized eggs were homogenized in a hypotonic medium which solubilized cytoplasmic antigens. Antigens integrated in membranes or enclosed in particles were solubilized by detergent treatment of the residual pellet. Two different phosphatase activities were discerned in the unfertilized eggs, nucleoside diphosphatase (EC 3.6.1.6.) and acid phosphatase (EC 3.1.3.2.). Nucleoside diphosphatase activity was obtained in both the water soluble and detergent extracted protein fractions. This activity was confined to one antigen. Acid phosphatase acitivity on the other hand was almost exclusively obtained in the detergent extracted fraction and about ten distinct antigens displayed this activity. The nucleoside diphosphatase active antigen preferentially hydrolyzed purine nucleoside diphosphates and to a lesser degree triphosphates of these nucleosides. The acid phosphatase active antigens had a broader substrate specificity and hydrolyzed equally well beta-glycerophosphate and nucleotides. Both activities were essentially inactive at neutral or alkaline pH values. The activities were inhibited by p-choloromercuribenzoate and accordingly stimulated by cysteine. Tartrate and sodium fluoride, however, inhibited the acid phosphatase activity while nucleoside diphosphatase activity was either stimulated or not affected at all by these agents."}
{"id": "PMID:237975", "title": "Phosphatase active antigens in sea urchin eggs and embryos. II. A comparison between the activities in unfertilized eggs and plutei.", "content": "Phosphatase activities in sea urchin eggs and plutei were investigated by means of histochemical staining of immunoprecipitates. Two protein fractions were obtained by extraction in a hypotonic medium and by detergent treatment of the residual pellet. Three distinctly different phosphatase activities were discerned, nucleoside diphosphatase (EC 3.6.1.6.), acid phosphatase (EC 3.1.3.2.) and alkaline phosphatase (EC 3.1.3.1.). The nucleoside diphosphatase activity, which was confined to one antigen, was present in both water soluble and detergent extracts and at roughly the same concentration in eggs and plutei. By means of a monospecific antiserum the immunological identify of this antigen was established in all instances. The acid phosphatase activity, which was displayed by ten detergent extracted antigens in eggs, was only found in five detergent extracted antigens in plutei. This decrease in number of enzyme active antigens was also reflected by a general decrease in number of enzyme active antigens was also reflected by a general decrease in activity as assessed by quantitative determinations. Furthermore, by means of absorbed antisera it was established that two or three of the acid phosphatase active antigens were \"egg specific\". Another acid phosphatase active antigen, which was common to both developmental stages, was investigated by a monospecific antiserum. While this antigen was found in both soluble fractions, it was only enzymatically active when extracted with detergent. Alkaline phosphatase active antigens were only found in the detergent extract of plutei. However, immunoprecipitates with this activity appeared both with antiserum against unfertilized eggs and with antiserum against plutei. This suggests that the egg contained the antigens in an enzymatically inactive form.", "contents": "Phosphatase active antigens in sea urchin eggs and embryos. II. A comparison between the activities in unfertilized eggs and plutei. Phosphatase activities in sea urchin eggs and plutei were investigated by means of histochemical staining of immunoprecipitates. Two protein fractions were obtained by extraction in a hypotonic medium and by detergent treatment of the residual pellet. Three distinctly different phosphatase activities were discerned, nucleoside diphosphatase (EC 3.6.1.6.), acid phosphatase (EC 3.1.3.2.) and alkaline phosphatase (EC 3.1.3.1.). The nucleoside diphosphatase activity, which was confined to one antigen, was present in both water soluble and detergent extracts and at roughly the same concentration in eggs and plutei. By means of a monospecific antiserum the immunological identify of this antigen was established in all instances. The acid phosphatase activity, which was displayed by ten detergent extracted antigens in eggs, was only found in five detergent extracted antigens in plutei. This decrease in number of enzyme active antigens was also reflected by a general decrease in number of enzyme active antigens was also reflected by a general decrease in activity as assessed by quantitative determinations. Furthermore, by means of absorbed antisera it was established that two or three of the acid phosphatase active antigens were \"egg specific\". Another acid phosphatase active antigen, which was common to both developmental stages, was investigated by a monospecific antiserum. While this antigen was found in both soluble fractions, it was only enzymatically active when extracted with detergent. Alkaline phosphatase active antigens were only found in the detergent extract of plutei. However, immunoprecipitates with this activity appeared both with antiserum against unfertilized eggs and with antiserum against plutei. This suggests that the egg contained the antigens in an enzymatically inactive form."}
{"id": "PMID:237976", "title": "Beta-lactamases from Yersinia enterocolitica.", "content": "Two beta-lactamases, A and B, have been shown to be present in a strain of Yersinia enterocolitica (w222). Beta-Lactamase A hydrolyses a variety of penicillins and cephalosporins. This enzyme is sensitive to thiol reagents, is only partially inhibited by 0-1 mM-cloxacillin and has a molecular weight of approximatley 20,000.beta-Lactamase B shows strong cephalosporinase activity but does not hydrolyse some of the penicillins. It is more resistant than beta-lactamase A to thiol reagents, is completely inhibited by 0-1 mM-cloxacillin and has a molecular weight of about 34,000. With cephaloridine as a substrate, which is readily hydrolysed by both enzymes, about 85% of the total activity of a cell extract is due to beta-lactamase A and 15% to B. Addition of 6-aminopenicillanic acid to the culture during growth results in a 2-to4-fold selective increase in the amount of beta-lactamase B. Two beta-lactamases similar to enzymes A and B have been found in five other strains of Y. enterocolitica. In contrast, only one beta-lactamase, similar to enzyme B, has been detected in a different strain of Y. enterocolitica (H66), which is abnormal in that it is sensitive to ampicillin. Addition of 6-aminopenicillanic acid to cultures of this strain results in an 8-to 10-fold increase in beta-lactamase production.", "contents": "Beta-lactamases from Yersinia enterocolitica. Two beta-lactamases, A and B, have been shown to be present in a strain of Yersinia enterocolitica (w222). Beta-Lactamase A hydrolyses a variety of penicillins and cephalosporins. This enzyme is sensitive to thiol reagents, is only partially inhibited by 0-1 mM-cloxacillin and has a molecular weight of approximatley 20,000.beta-Lactamase B shows strong cephalosporinase activity but does not hydrolyse some of the penicillins. It is more resistant than beta-lactamase A to thiol reagents, is completely inhibited by 0-1 mM-cloxacillin and has a molecular weight of about 34,000. With cephaloridine as a substrate, which is readily hydrolysed by both enzymes, about 85% of the total activity of a cell extract is due to beta-lactamase A and 15% to B. Addition of 6-aminopenicillanic acid to the culture during growth results in a 2-to4-fold selective increase in the amount of beta-lactamase B. Two beta-lactamases similar to enzymes A and B have been found in five other strains of Y. enterocolitica. In contrast, only one beta-lactamase, similar to enzyme B, has been detected in a different strain of Y. enterocolitica (H66), which is abnormal in that it is sensitive to ampicillin. Addition of 6-aminopenicillanic acid to cultures of this strain results in an 8-to 10-fold increase in beta-lactamase production."}
{"id": "PMID:237977", "title": "Temperature-sensitive mutants of foot-and-mouth disease virus: the isolation of mutants and observations on their properties and genetic recombination.", "content": "A number of temperature-sensitive mutants were isolated from two strains of foot-and-mouth disease virus (FMDV). Various properties of the mutants were examined including comparative growth curves at permissive and restrictive temperatures, cut-off temperatures, thermal lability and pH sensitivity. Recombination was observed between various pairs of mutants of FMDV strain Pacheco. It occurred early in the growth cycle and the proportion of recombinants remained constant thereafter. Maximum recombination was achieved if the input multiplicity of each virus was 6 p.f.u./cell or greater, provided the ratio of the input multiplicities did not vary by more than a factor of two. Day-to-day variations could be substantially reduced by normalizing recombination frequencies in terms of a standard cross. The results suggested that genetic mapping was possible with two-or three-factor crosses.", "contents": "Temperature-sensitive mutants of foot-and-mouth disease virus: the isolation of mutants and observations on their properties and genetic recombination. A number of temperature-sensitive mutants were isolated from two strains of foot-and-mouth disease virus (FMDV). Various properties of the mutants were examined including comparative growth curves at permissive and restrictive temperatures, cut-off temperatures, thermal lability and pH sensitivity. Recombination was observed between various pairs of mutants of FMDV strain Pacheco. It occurred early in the growth cycle and the proportion of recombinants remained constant thereafter. Maximum recombination was achieved if the input multiplicity of each virus was 6 p.f.u./cell or greater, provided the ratio of the input multiplicities did not vary by more than a factor of two. Day-to-day variations could be substantially reduced by normalizing recombination frequencies in terms of a standard cross. The results suggested that genetic mapping was possible with two-or three-factor crosses."}
{"id": "PMID:237989", "title": "Sites of organic acid production and pattern of digesta movement in the gastrointestinal tract of swine.", "content": "Twelve swine were used to assess the movement of fluid and particulate digesta through their gastrointestinal tracts and to determine the diurnal variations in organic acid levels for various segments of the tract. Animals were fed twice daily at 12-hour intervals. Fluid (polyethylene glycol and chromium-labeled ethylenediamine-tetraacetic acid) and particulate markers (2 mm OD, and 2 mm and 1 and 2 cm long) were administration of markers. The gastrointestinal tract was divided into 12 segments for measurements of markers, pH, volatile fatty acids (VFA), and lactic acid (LA) contents. The data indicated a rapid evacuation of the fluid and the smaller particles from the stomach and their relatively rapid passage through the small intestine and cecum. There was, however, prolonged retention of both fluid and particulate markers first in the ascending and then in the descending colon. Larger particles (2 cm) were retained in the stomach throughout much of the 60-hour experimental period. LA levels were observed 8 hours postfeeding. The highest levels of VFA in gastric contents averaged 20 mmoles/liter. Gastrointestinal pH values showed significant changes with time postfeeding only within the stomach, where they did not reflect the changes in LA of VFA concentrations. VFA constituted 92% of the organic acids present in the large intestine. Their concentrations varied markedly with time (150-230 mmoles/liter), but the VFA at all times constituted the major anions in the large intestinal contents. The results demonstrated that digesta can be retained for prolonged periods of time in that swine stomach and colon. The high concentrations of organic acids also indicated that substantial degrees of microbial digestion of carbohydrates occurred at both sites.", "contents": "Sites of organic acid production and pattern of digesta movement in the gastrointestinal tract of swine. Twelve swine were used to assess the movement of fluid and particulate digesta through their gastrointestinal tracts and to determine the diurnal variations in organic acid levels for various segments of the tract. Animals were fed twice daily at 12-hour intervals. Fluid (polyethylene glycol and chromium-labeled ethylenediamine-tetraacetic acid) and particulate markers (2 mm OD, and 2 mm and 1 and 2 cm long) were administration of markers. The gastrointestinal tract was divided into 12 segments for measurements of markers, pH, volatile fatty acids (VFA), and lactic acid (LA) contents. The data indicated a rapid evacuation of the fluid and the smaller particles from the stomach and their relatively rapid passage through the small intestine and cecum. There was, however, prolonged retention of both fluid and particulate markers first in the ascending and then in the descending colon. Larger particles (2 cm) were retained in the stomach throughout much of the 60-hour experimental period. LA levels were observed 8 hours postfeeding. The highest levels of VFA in gastric contents averaged 20 mmoles/liter. Gastrointestinal pH values showed significant changes with time postfeeding only within the stomach, where they did not reflect the changes in LA of VFA concentrations. VFA constituted 92% of the organic acids present in the large intestine. Their concentrations varied markedly with time (150-230 mmoles/liter), but the VFA at all times constituted the major anions in the large intestinal contents. The results demonstrated that digesta can be retained for prolonged periods of time in that swine stomach and colon. The high concentrations of organic acids also indicated that substantial degrees of microbial digestion of carbohydrates occurred at both sites."}
{"id": "PMID:237990", "title": "Effects of dietary calcium level, acid stress, and age on renal, serum, and bone responses of rats.", "content": "The effects of age and acid stress on renal, serum and bone responses in 13- and 25-month-old rats, which were fed two levels of dietary calcium, 100 and 500 mg/100 g of diet, for 9 months, with and without dietary ammonium chloride (2%), were investigated. Acid-stressed animals showed significant decreases in urinary pH and significant increases in urinary total acid, calcium and phosphorus excretions, kidney weights, and phosphate-dependent glutaminase activities. Renal responses were affected by the level of calcium in the diet and the age of the animal. Acid stress tended to decrease serum calcium and phosphorus. Serum phosphorus was decreased in old animals, while serum calcium was unaffected by age. Tibia ash weights of old animals were significantly less and their fat content was significantly higher than that of young animals. However, neither acid stress nor the level of calcium in the diet significantly affected bone analysis in either age group.", "contents": "Effects of dietary calcium level, acid stress, and age on renal, serum, and bone responses of rats. The effects of age and acid stress on renal, serum and bone responses in 13- and 25-month-old rats, which were fed two levels of dietary calcium, 100 and 500 mg/100 g of diet, for 9 months, with and without dietary ammonium chloride (2%), were investigated. Acid-stressed animals showed significant decreases in urinary pH and significant increases in urinary total acid, calcium and phosphorus excretions, kidney weights, and phosphate-dependent glutaminase activities. Renal responses were affected by the level of calcium in the diet and the age of the animal. Acid stress tended to decrease serum calcium and phosphorus. Serum phosphorus was decreased in old animals, while serum calcium was unaffected by age. Tibia ash weights of old animals were significantly less and their fat content was significantly higher than that of young animals. However, neither acid stress nor the level of calcium in the diet significantly affected bone analysis in either age group."}
{"id": "PMID:237991", "title": "Changes in fatty acid synthesis and lipogenic enzymes in adipose tissue from fasted and fasted-refed steers.", "content": "Controls of fatty acid synthesis in bovine adipose tissue were investigated. Six Brown Swiss steers were fasted for 8 days and then refed for 56 days. Biopsy samples of backfat adipose tissue were taken during the fasting and refeeding periods. Rates of acetate incorporation into fatty acids (FAS), activities of acetyl CoA carboxylase (CBX), glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and NADP:isocitrate dehydrogenase, and plasma free fatty acids (FFA) and plasma acetate were determined. FAS decreased 60% after 1 day of fasting and 99% after 8 days. FAS did not increase until day 3 of refeeding when energy intake was above maintenance, then returned to normal by 14 days. CBX followed a pattern similar to FAS, except its activity did rise above the control rate during refeeding. Plasma FFA increased 350% and acetate decreased 67% during fasting. After 4 days of refeeding, FFA returned to normal, and acetate increased to 156% of initial concentration, then returned to normal by 21 days. These data suggest that CBX limits FAS in adipose tissue of cattle.", "contents": "Changes in fatty acid synthesis and lipogenic enzymes in adipose tissue from fasted and fasted-refed steers. Controls of fatty acid synthesis in bovine adipose tissue were investigated. Six Brown Swiss steers were fasted for 8 days and then refed for 56 days. Biopsy samples of backfat adipose tissue were taken during the fasting and refeeding periods. Rates of acetate incorporation into fatty acids (FAS), activities of acetyl CoA carboxylase (CBX), glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and NADP:isocitrate dehydrogenase, and plasma free fatty acids (FFA) and plasma acetate were determined. FAS decreased 60% after 1 day of fasting and 99% after 8 days. FAS did not increase until day 3 of refeeding when energy intake was above maintenance, then returned to normal by 14 days. CBX followed a pattern similar to FAS, except its activity did rise above the control rate during refeeding. Plasma FFA increased 350% and acetate decreased 67% during fasting. After 4 days of refeeding, FFA returned to normal, and acetate increased to 156% of initial concentration, then returned to normal by 21 days. These data suggest that CBX limits FAS in adipose tissue of cattle."}
{"id": "PMID:237995", "title": "The influence of cosolvents and substrate substituents on the sorption of benzoic acid derivatives by polyamides.", "content": "The sorption of some substituted benzoic acid derivatives by polyamides (nylons) from aqueous solution has been examined and the influence of their nature together with those of the cosolvent and polymer have been assessed. In all cases the sorption isotherms were linear and could be expressed by a simple distribution law, enabling the influence of cosolvent concentration to be predicted. The sorption of a series of p-substituted benzoic acids and some of their esters is related to their solubility except where the p-substituent is capable of hydrogen-bonding with the polymer. The extent of the interaction is also dependent upon the amide frequency of the polymer.", "contents": "The influence of cosolvents and substrate substituents on the sorption of benzoic acid derivatives by polyamides. The sorption of some substituted benzoic acid derivatives by polyamides (nylons) from aqueous solution has been examined and the influence of their nature together with those of the cosolvent and polymer have been assessed. In all cases the sorption isotherms were linear and could be expressed by a simple distribution law, enabling the influence of cosolvent concentration to be predicted. The sorption of a series of p-substituted benzoic acids and some of their esters is related to their solubility except where the p-substituent is capable of hydrogen-bonding with the polymer. The extent of the interaction is also dependent upon the amide frequency of the polymer."}
{"id": "PMID:237996", "title": "Non-ionic surfactants and membrane transport of thioridazine in goldfish.", "content": "Polysorbate 80, which has been widely used in studies of the effects of surfactants on drug absorption, increases the rate of absorption of some drugs at concentrations near its critical micelle concentration (cmc). To determine whether all non-ionic surfactants were capable of inducing this effect, the effects of six commercial non-ionic surfactants on thioridazine absorption in goldfish have been compared with the effect of polysorbate 80. The reciprocal death time (T-1) determined when the fish were immersed in the solution under study was the index of absoprtion rate used. Not all surfactants tested increased T-1. Cremophor EL (polyoxyethylated castor oil), Atlas G1295 (a polyoxyethylene fatty glyceride), Atlas G1300 (a polyoxyethylene glyceride ester) had no effect below their cmc's. Those surfactants that did increase T-1 [polysorbate 80 (a polyoxyethylene lanolin derivative), G2162 (a polyoxyethylene oxypropylene monosterate) and Renex 650 (a polyoxyethylene alkyl aryl ether)] display the concentration-dependent behaviour reported previously - a decrease in absorption rate when the surfactant concentration is increased above its cmc. The factor determining whether or not the surfactant will increas absorption rate appears to be the configuration of the surfactant molecule rather than its hydrophile-lipophile balance or its surface activity.", "contents": "Non-ionic surfactants and membrane transport of thioridazine in goldfish. Polysorbate 80, which has been widely used in studies of the effects of surfactants on drug absorption, increases the rate of absorption of some drugs at concentrations near its critical micelle concentration (cmc). To determine whether all non-ionic surfactants were capable of inducing this effect, the effects of six commercial non-ionic surfactants on thioridazine absorption in goldfish have been compared with the effect of polysorbate 80. The reciprocal death time (T-1) determined when the fish were immersed in the solution under study was the index of absoprtion rate used. Not all surfactants tested increased T-1. Cremophor EL (polyoxyethylated castor oil), Atlas G1295 (a polyoxyethylene fatty glyceride), Atlas G1300 (a polyoxyethylene glyceride ester) had no effect below their cmc's. Those surfactants that did increase T-1 [polysorbate 80 (a polyoxyethylene lanolin derivative), G2162 (a polyoxyethylene oxypropylene monosterate) and Renex 650 (a polyoxyethylene alkyl aryl ether)] display the concentration-dependent behaviour reported previously - a decrease in absorption rate when the surfactant concentration is increased above its cmc. The factor determining whether or not the surfactant will increas absorption rate appears to be the configuration of the surfactant molecule rather than its hydrophile-lipophile balance or its surface activity."}
{"id": "PMID:237997", "title": "Surface tension and cloud point changes of polyoxyethylenic non-ionic surfactants during autoxidation.", "content": "Changes in the surface tension-concentration curves of the non-ionic surfactant cetomacrogol, a polyoxyethylenic (POE) hexadecyl ether containing about 24 ethylene oxide (EO) groups, have been examined during autoxidation of aqueous solutions. The curves exhibit decreases in cmc values and changes in the slopes below and above the cmc which lead to the loss of the sharp break characteristic of micelle-formation. There is also a progressive decrease in the cloud point during autoxidation. Surface tensions and cloud points of a series of known POE hexadecyl ethers containing from 10 to 60 EO units have been measured and related to the number of EO units present. From these data, it is apparent that autoxidation of cetomacrogol is accompanied by degradation of POE chain rather than the hydrocarbon chain, the number of EO units lost up to the time at which the solution becomes turbid being about 14. The significance of such measurements is discussed in relation to the detection of decomposition and pending rapid decomposition in synthesized and commercial surfactants.", "contents": "Surface tension and cloud point changes of polyoxyethylenic non-ionic surfactants during autoxidation. Changes in the surface tension-concentration curves of the non-ionic surfactant cetomacrogol, a polyoxyethylenic (POE) hexadecyl ether containing about 24 ethylene oxide (EO) groups, have been examined during autoxidation of aqueous solutions. The curves exhibit decreases in cmc values and changes in the slopes below and above the cmc which lead to the loss of the sharp break characteristic of micelle-formation. There is also a progressive decrease in the cloud point during autoxidation. Surface tensions and cloud points of a series of known POE hexadecyl ethers containing from 10 to 60 EO units have been measured and related to the number of EO units present. From these data, it is apparent that autoxidation of cetomacrogol is accompanied by degradation of POE chain rather than the hydrocarbon chain, the number of EO units lost up to the time at which the solution becomes turbid being about 14. The significance of such measurements is discussed in relation to the detection of decomposition and pending rapid decomposition in synthesized and commercial surfactants."}
{"id": "PMID:237998", "title": "Isolation, characterization and quantitation of chloral hydrate as a transient metabolite of trichloroethylene in man using electron capture gas chromatography and mass fragmentography.", "content": "A method for the quantitative determination of plasma concentrations of chloral hydrate by electron capture gas chromatography is described. Characterization by multiple ion monitoring confirms, for the first time, that chloral hydrate exists as a transient metabolite of trichloroethylene in man.", "contents": "Isolation, characterization and quantitation of chloral hydrate as a transient metabolite of trichloroethylene in man using electron capture gas chromatography and mass fragmentography. A method for the quantitative determination of plasma concentrations of chloral hydrate by electron capture gas chromatography is described. Characterization by multiple ion monitoring confirms, for the first time, that chloral hydrate exists as a transient metabolite of trichloroethylene in man."}
{"id": "PMID:237999", "title": "Quantitative determination of morphine in biological samples by gas-liquid chromatography and electron-capture detection.", "content": "A highly sensitive method for the determination of morphine in plasma and brain samples down to 500 pg ml-1 in plasma and 100 pg in 30 mg of brain tissue is described. This sensitivity is in the range of that described for radioactive and radioimmunological tehcniques. The samples (50-500 mu-l) are extracted with toluene-butanol (9:1) at pH 8.9 and then re-extracted into 0.1 N sulphuric acid and back extracted to a toluene-butanol phase at pH 8.9. The pentafluoropropionic anhydride derivatives of morphine and the internal standard nalorphine were quantitatively determined by gas-liquid chromatography with a 3-H electron capture detector.", "contents": "Quantitative determination of morphine in biological samples by gas-liquid chromatography and electron-capture detection. A highly sensitive method for the determination of morphine in plasma and brain samples down to 500 pg ml-1 in plasma and 100 pg in 30 mg of brain tissue is described. This sensitivity is in the range of that described for radioactive and radioimmunological tehcniques. The samples (50-500 mu-l) are extracted with toluene-butanol (9:1) at pH 8.9 and then re-extracted into 0.1 N sulphuric acid and back extracted to a toluene-butanol phase at pH 8.9. The pentafluoropropionic anhydride derivatives of morphine and the internal standard nalorphine were quantitatively determined by gas-liquid chromatography with a 3-H electron capture detector."}
{"id": "PMID:238000", "title": "Dextromethorphan inhibits 5-hydroxytryptamine uptake by human blood platelets and decreases 5-hydroxyindoleacetic acid content in rat brain.", "content": "The effect of dextromethorphan on the uptake and metabolism of 5-hydroxytryptamine (5-HT) was studied in human blood platelets and in rat brain. In the concentration of 120 nM dextromethorphan inhibited the uptake of 5-HT (1 mu-M) into platelets by 50%. The corresponding concentrations of imipramine and methadone under similar conditions were 22 and 590 nM, respectively. Dextromethorphan (20 to 40 mg kg-1) decreased the concentration of brain 5-hydroxyindoleacetic acid (5-HIAA) and the probenecid-induced accumulation of 5-HIAA time- and dose-dependently. However, dextromethorphan did not alter the pargyline-induced changes in brain 5-HT metabolism. Dextromethorphan-induced changes in brain 5-HT metabolism could arise from the inhibition of the re-uptake of 5-HT into neurons.", "contents": "Dextromethorphan inhibits 5-hydroxytryptamine uptake by human blood platelets and decreases 5-hydroxyindoleacetic acid content in rat brain. The effect of dextromethorphan on the uptake and metabolism of 5-hydroxytryptamine (5-HT) was studied in human blood platelets and in rat brain. In the concentration of 120 nM dextromethorphan inhibited the uptake of 5-HT (1 mu-M) into platelets by 50%. The corresponding concentrations of imipramine and methadone under similar conditions were 22 and 590 nM, respectively. Dextromethorphan (20 to 40 mg kg-1) decreased the concentration of brain 5-hydroxyindoleacetic acid (5-HIAA) and the probenecid-induced accumulation of 5-HIAA time- and dose-dependently. However, dextromethorphan did not alter the pargyline-induced changes in brain 5-HT metabolism. Dextromethorphan-induced changes in brain 5-HT metabolism could arise from the inhibition of the re-uptake of 5-HT into neurons."}
{"id": "PMID:238001", "title": "Evidence for a central alpha-sympathomimetic action of clonidine in the rat.", "content": "The antihypertensive effects of clonidine (0.15 mg kg-1, i.p.) were studied in conscious DOCA/saline hypertensive rats having chronically implanted arterial cannulae. The response to clonidine was markedly reduced by simultaneously administered desipramine (3 mg kg-1, i.p.), antagonized dose-dependently by piperoxan (2-10 mg kg-1, i.v.) and prevented by pretreatment with phentolamine (0.2 mg, i.c.v.). Pretreatment with 6-hydroxydopamine (3 x 250 mu-g, i.c.v.), haloperidol (1 mg kg-1, i.p.), p-chloro-N-methylamphetamine (3.5 mg kg-1, i.p.) or 5,6-dihydroxytryptamine (50 mu-g and 25 mu-g, i.c.v.) did not significantly modify the antihypertensive response. It is concluded that the antihypertensive response to clonidine is mediated via stimulation of central alpha-adrenoceptors and is independent of central dopaminergic receptors and intact central serotoninergic neurons. The necessity for intact central noradrenergic neurons remains uncertain.", "contents": "Evidence for a central alpha-sympathomimetic action of clonidine in the rat. The antihypertensive effects of clonidine (0.15 mg kg-1, i.p.) were studied in conscious DOCA/saline hypertensive rats having chronically implanted arterial cannulae. The response to clonidine was markedly reduced by simultaneously administered desipramine (3 mg kg-1, i.p.), antagonized dose-dependently by piperoxan (2-10 mg kg-1, i.v.) and prevented by pretreatment with phentolamine (0.2 mg, i.c.v.). Pretreatment with 6-hydroxydopamine (3 x 250 mu-g, i.c.v.), haloperidol (1 mg kg-1, i.p.), p-chloro-N-methylamphetamine (3.5 mg kg-1, i.p.) or 5,6-dihydroxytryptamine (50 mu-g and 25 mu-g, i.c.v.) did not significantly modify the antihypertensive response. It is concluded that the antihypertensive response to clonidine is mediated via stimulation of central alpha-adrenoceptors and is independent of central dopaminergic receptors and intact central serotoninergic neurons. The necessity for intact central noradrenergic neurons remains uncertain."}
{"id": "PMID:238002", "title": "Comparison of the time course of the anorectic effect of fenfluramine and amphetamine with drug levels in blood.", "content": "Time courses of the suppressive effects on food intake of (+)-amphetamine and (plus or minus)-fenfluramine in deprived rats were found to be different. Amphetamine displayed a potent initial action which rapidly decayed, and this behavioural effect was consistent with the measured blood concentration of amphetamine which showed a peak at 1 h followed by rapid clearance. For fenfluramine, the initial suppression of eating was maintained over several hours and was, for the first hour, related to the blood concentration of fenfluramine but later to an active metabolite, norfenfluramine. The study shows how drug-induced changes in feeding behaviour fluctuate over time and illustrate how single measures of food intake may overlook information about the effectiveness of anorectic drugs.", "contents": "Comparison of the time course of the anorectic effect of fenfluramine and amphetamine with drug levels in blood. Time courses of the suppressive effects on food intake of (+)-amphetamine and (plus or minus)-fenfluramine in deprived rats were found to be different. Amphetamine displayed a potent initial action which rapidly decayed, and this behavioural effect was consistent with the measured blood concentration of amphetamine which showed a peak at 1 h followed by rapid clearance. For fenfluramine, the initial suppression of eating was maintained over several hours and was, for the first hour, related to the blood concentration of fenfluramine but later to an active metabolite, norfenfluramine. The study shows how drug-induced changes in feeding behaviour fluctuate over time and illustrate how single measures of food intake may overlook information about the effectiveness of anorectic drugs."}
{"id": "PMID:238003", "title": "How does angiotensin II increase cardiac dopamine-beta-hydroxylation?", "content": "The potent accelerating effect of angiotensin II (Ang II) on caridac dopamine beta-hydroxylation was studied on slices of rat heart. Ang II did not affect the kinetics of beta-hydroxylation but it increased the axonal uptake of dopamine, and, concomitant with the acceleration of biosynthesis, it enhanced the accumulation of dopamine into tissue. Puromycin, in contrast to actinomycin D, antagonized the stimulation of dopamine beta-hydroxylation by Ang II, but did not suppress the rise in cardiac dopamine. Therefore, to promote the acceleration of dopamine beta-hydroxylation, (i) the rise in tissue dopamine available for conversion appeared to be insufficient, (ii) the formation of new proteins by activation of traduction seemed to constitute the basic mechanism of Ang II action.", "contents": "How does angiotensin II increase cardiac dopamine-beta-hydroxylation? The potent accelerating effect of angiotensin II (Ang II) on caridac dopamine beta-hydroxylation was studied on slices of rat heart. Ang II did not affect the kinetics of beta-hydroxylation but it increased the axonal uptake of dopamine, and, concomitant with the acceleration of biosynthesis, it enhanced the accumulation of dopamine into tissue. Puromycin, in contrast to actinomycin D, antagonized the stimulation of dopamine beta-hydroxylation by Ang II, but did not suppress the rise in cardiac dopamine. Therefore, to promote the acceleration of dopamine beta-hydroxylation, (i) the rise in tissue dopamine available for conversion appeared to be insufficient, (ii) the formation of new proteins by activation of traduction seemed to constitute the basic mechanism of Ang II action."}
{"id": "PMID:238015", "title": "Fluorescence characteristics of benzodiazepines in strong acid.", "content": "The fluorescence characteristics of 10 substituted 1,4-benzodiazepines in strong acid solution were investigated. The compounds that fluoresce in the Hammett acidity region possess, or can form by enolization, an azomethine linkage in the 1,2- or 4,5-position. All benzodiazepines that fluoresce in strong acid show increases in fluorescence intensity with corresponding blue shifts as acidity increases. Two pKa's in the Hammett acidity region were observed for both the fluorometric and absorptiometric titrations of the benzodiazepines possessing a carbonyl in the 2-position. No evidence of excited state prototropism was observed.", "contents": "Fluorescence characteristics of benzodiazepines in strong acid. The fluorescence characteristics of 10 substituted 1,4-benzodiazepines in strong acid solution were investigated. The compounds that fluoresce in the Hammett acidity region possess, or can form by enolization, an azomethine linkage in the 1,2- or 4,5-position. All benzodiazepines that fluoresce in strong acid show increases in fluorescence intensity with corresponding blue shifts as acidity increases. Two pKa's in the Hammett acidity region were observed for both the fluorometric and absorptiometric titrations of the benzodiazepines possessing a carbonyl in the 2-position. No evidence of excited state prototropism was observed."}
{"id": "PMID:238016", "title": "Determination of estrogens in dosage forms by fluorescence using dansyl chloride.", "content": "A sensitive, reproducible, fluorometric procedure for the determination of estrogens in pharmaceutical preparations is presented. The estrogens are determined fluorometrically following their reaction with dansyl chloride. The optimum conditions for the reaction such as pH, reaction solvent composition variations, and speed of reaction are discussed. In addition, a linearity study of the relationship between concentration and fluorescence intensity for estrone, estradiol, and ethinyl estradiol is reported. Solvent extraction procedures based on acid-base behavior or column chromatography are used when necessary to isolate the estrogen prior to reaction with dansyl chloride and fluorometric measurement. The recovery of estrogens from spiked samples indicated that the proposed method is efficient and reproducible. Comparison of the dansyl procedure with the official NF method in the analysis of estrone aqueous suspension showed the proposed method to be accurate and more precise than the NF assay. Estrone aqueous suspension, estradiol in sesame oil, estradiol valerate in castor oil and in sesame oil (in the latter case, in the presence of testosterone), estradiol benzoate in sesame oil, and ethinyl estradiol tablets (0.5 mg/tablet) from commercial sources were satisfactorily analyzed, with average results within compendial limits and no coefficient of variation greater than 2%.", "contents": "Determination of estrogens in dosage forms by fluorescence using dansyl chloride. A sensitive, reproducible, fluorometric procedure for the determination of estrogens in pharmaceutical preparations is presented. The estrogens are determined fluorometrically following their reaction with dansyl chloride. The optimum conditions for the reaction such as pH, reaction solvent composition variations, and speed of reaction are discussed. In addition, a linearity study of the relationship between concentration and fluorescence intensity for estrone, estradiol, and ethinyl estradiol is reported. Solvent extraction procedures based on acid-base behavior or column chromatography are used when necessary to isolate the estrogen prior to reaction with dansyl chloride and fluorometric measurement. The recovery of estrogens from spiked samples indicated that the proposed method is efficient and reproducible. Comparison of the dansyl procedure with the official NF method in the analysis of estrone aqueous suspension showed the proposed method to be accurate and more precise than the NF assay. Estrone aqueous suspension, estradiol in sesame oil, estradiol valerate in castor oil and in sesame oil (in the latter case, in the presence of testosterone), estradiol benzoate in sesame oil, and ethinyl estradiol tablets (0.5 mg/tablet) from commercial sources were satisfactorily analyzed, with average results within compendial limits and no coefficient of variation greater than 2%."}
{"id": "PMID:238017", "title": "In vitro antibacterial activity of drugs against human intestinal anaerobic bacteria.", "content": "The in vitro antibacterial activity, against the major groups of anaerobic fecal bacteria, of a series of drugs was examined by an agar diffusion test and the minimum inhibitory concentration (MIC) test. Only the phenothiazines and amitriptyline showed any marked antibacterial activity, the MIC's being in the 40-640-mu-g/ml range. It is suggested that the detergent nature of the molecules of these drugs in aqueous solution is responsible for the observed antibacterial activity.", "contents": "In vitro antibacterial activity of drugs against human intestinal anaerobic bacteria. The in vitro antibacterial activity, against the major groups of anaerobic fecal bacteria, of a series of drugs was examined by an agar diffusion test and the minimum inhibitory concentration (MIC) test. Only the phenothiazines and amitriptyline showed any marked antibacterial activity, the MIC's being in the 40-640-mu-g/ml range. It is suggested that the detergent nature of the molecules of these drugs in aqueous solution is responsible for the observed antibacterial activity."}
{"id": "PMID:238019", "title": "Effect of beta receptor blockade on the initiation and perpetuation of ouabain-induced ventricular tachyarrhythmia.", "content": "The role of the cardiac beta receptor in the genesis and perpetuation of ouabain-induced ventricular tachyarrhythmias (VT) was investigated in the chloralose (20 mg/kg)-urethane (200 mg/kg) anesthetized dog. This was achieved by determining: 1) the effect of oxprenolol (0.3 mg/kg), a potent beta receptor blocking agent possessing no significant direct membrane effects on the myocardium, on the dose of ouabain necessary to cause VT (i.e., the toxic dose); and 2) whether oxprenolol had antirrhythmic efficacy against preexisting VT. The toxic dose was determined by giving a bolus injection of ouabain (similar to 36 mug/kg) plus a subsequent ouabain infusion (similar to 0.40 mug/kg min-minus 1) until VT occurred. VT was defined as at least one-third of the ventricular beats being of ectopic ventricular origin. The existence of an effective beta receptor blockade was verified by showing that 0.75 mug/kg of isoproterenol (an ED50 dose) injected intravenously had no detectable cardiovascular effects. The results were: 1) oxprenolol (0.3 mg/kg) did not alter the toxic dose significantly (P greater than .5 for both paired and group comparisons) [63.9 plus or minus 2.3 (S.E.) mug/kg vs. 64.4 plus or minus 2.9 (S.E.) mug/kg]; and 2) attempts to convert VT to sinus rhythm with oxprenolol (0.3 mg/kg) failed in 20 of 21 trials. Oxprenolol (1.0 mg/kg) effected only a temporary [10.6 plus or minus 6.4 (S.D.) minutes] reversion to sinus rhythm in 10 of 21 attempts. These results indicate that an activation of the cardiac beta receptor is not prerequisite for either the initiation or the perpetuation of ouabain-induced ventricular tachyarrhythmia in this particular model. The results cannot provide support for the notion that an increase in cardiac sympathetic nerve activity is a principal factor in VT in the dog. However, the results are consistent with the hypothesis that the direct membrane actions of ouabain are a principal cause of ouabain-induced ventricular tachyarrhythmia.", "contents": "Effect of beta receptor blockade on the initiation and perpetuation of ouabain-induced ventricular tachyarrhythmia. The role of the cardiac beta receptor in the genesis and perpetuation of ouabain-induced ventricular tachyarrhythmias (VT) was investigated in the chloralose (20 mg/kg)-urethane (200 mg/kg) anesthetized dog. This was achieved by determining: 1) the effect of oxprenolol (0.3 mg/kg), a potent beta receptor blocking agent possessing no significant direct membrane effects on the myocardium, on the dose of ouabain necessary to cause VT (i.e., the toxic dose); and 2) whether oxprenolol had antirrhythmic efficacy against preexisting VT. The toxic dose was determined by giving a bolus injection of ouabain (similar to 36 mug/kg) plus a subsequent ouabain infusion (similar to 0.40 mug/kg min-minus 1) until VT occurred. VT was defined as at least one-third of the ventricular beats being of ectopic ventricular origin. The existence of an effective beta receptor blockade was verified by showing that 0.75 mug/kg of isoproterenol (an ED50 dose) injected intravenously had no detectable cardiovascular effects. The results were: 1) oxprenolol (0.3 mg/kg) did not alter the toxic dose significantly (P greater than .5 for both paired and group comparisons) [63.9 plus or minus 2.3 (S.E.) mug/kg vs. 64.4 plus or minus 2.9 (S.E.) mug/kg]; and 2) attempts to convert VT to sinus rhythm with oxprenolol (0.3 mg/kg) failed in 20 of 21 trials. Oxprenolol (1.0 mg/kg) effected only a temporary [10.6 plus or minus 6.4 (S.D.) minutes] reversion to sinus rhythm in 10 of 21 attempts. These results indicate that an activation of the cardiac beta receptor is not prerequisite for either the initiation or the perpetuation of ouabain-induced ventricular tachyarrhythmia in this particular model. The results cannot provide support for the notion that an increase in cardiac sympathetic nerve activity is a principal factor in VT in the dog. However, the results are consistent with the hypothesis that the direct membrane actions of ouabain are a principal cause of ouabain-induced ventricular tachyarrhythmia."}
{"id": "PMID:238020", "title": "Antihypertensive drugs and catecholamine metabolism: effects of reserpine and hydralazine on tyrosine hydroxylase activity and norepinephrine concentrations in the spontaneously hypertensive rat.", "content": "The antihypertensive drugs, reserpine and hydralazine, produce different effects on tyrosine hydroxylase activity and norepinephrine levels in blood vessels and other tissues of the spontaneously hypertensive rat at doses which cause an equivalent reduction in blood pressure. Reserpine administration is associated with increased tyrosine hydroxylase activity in the mesenteric artery, mesenteric vein and adrenal, but the vasculature appears more sensitive to the effects of reserpine than the adrenal. This increase in tyrosine hydroxylase activity can be related to catecholamine depletion in the mesenteric artery, mesenteric vein and adrenal. Since chlorisondamine, a ganglionic blocking agent, diminished the ability of reserpine to increase tyrosine hydroxylase activity in the mesenteric artery and adrenal, it is likely that increased nerve activity is involved in regulation of the enzyme in both tissues. Hydralazine neither alters tyrosine hydroxylase activity in arteries or veins, nor depletes catecholamine levels in these tissues. In the adrenal, hydralazine increases tyrosine hydroxylase activity independently of any change in catecholamine levels. It would appear that changes in tyrosine hydroxylase activity produced by antihypertensive drugs are organ dependent and may involve both neuronal activity and amine depletion.", "contents": "Antihypertensive drugs and catecholamine metabolism: effects of reserpine and hydralazine on tyrosine hydroxylase activity and norepinephrine concentrations in the spontaneously hypertensive rat. The antihypertensive drugs, reserpine and hydralazine, produce different effects on tyrosine hydroxylase activity and norepinephrine levels in blood vessels and other tissues of the spontaneously hypertensive rat at doses which cause an equivalent reduction in blood pressure. Reserpine administration is associated with increased tyrosine hydroxylase activity in the mesenteric artery, mesenteric vein and adrenal, but the vasculature appears more sensitive to the effects of reserpine than the adrenal. This increase in tyrosine hydroxylase activity can be related to catecholamine depletion in the mesenteric artery, mesenteric vein and adrenal. Since chlorisondamine, a ganglionic blocking agent, diminished the ability of reserpine to increase tyrosine hydroxylase activity in the mesenteric artery and adrenal, it is likely that increased nerve activity is involved in regulation of the enzyme in both tissues. Hydralazine neither alters tyrosine hydroxylase activity in arteries or veins, nor depletes catecholamine levels in these tissues. In the adrenal, hydralazine increases tyrosine hydroxylase activity independently of any change in catecholamine levels. It would appear that changes in tyrosine hydroxylase activity produced by antihypertensive drugs are organ dependent and may involve both neuronal activity and amine depletion."}
{"id": "PMID:238021", "title": "Mechanical response in the wall of ovarian follicles mediated by adrenergic receptors.", "content": "The identity of the adrenergic receptors involved in the contractility of the follicular wall was studied in bovine ovaries. Strips were prepared mainly from the protruding part of large Graafian follicles and mounted in an organ bath for recording of mechanical activity. Some intact ovaries and strips from the bottom of follicles were also studied. The latter two preparations showed spontaneous rhythmic contractions, and the tension was increased by norepinephrine and reduced by terbutaline. Norepinephrine, epinephrine, phenylephrine, isoproterenol and terbutaline alone or in combination with various concentrations of the inhibitors, phenoxybenzamine, piperoxan and propranolol, were used to analyze adrenoceptors in strips from the protruding portion of the follicle. Such strips showed no appreciable spontaneous contractions. A contractile response was found to be mediated by alpha receptors. The KA value for norepinephrine (determined in combination with phenoxybenzamine) was found to be 2.26 X 10- minus 6 M and KB for piperoxan (determined in combination with norepinephrine) was 1.02 X 10-minus 8 M (pA2 = 8.19). Adrenergic beta receptors mediated relaxation of the strips, and the KB value for propranolol (determined in combination with terbutaline) was 7.28 X 10-minus 9 M (pA2 = 8.17).", "contents": "Mechanical response in the wall of ovarian follicles mediated by adrenergic receptors. The identity of the adrenergic receptors involved in the contractility of the follicular wall was studied in bovine ovaries. Strips were prepared mainly from the protruding part of large Graafian follicles and mounted in an organ bath for recording of mechanical activity. Some intact ovaries and strips from the bottom of follicles were also studied. The latter two preparations showed spontaneous rhythmic contractions, and the tension was increased by norepinephrine and reduced by terbutaline. Norepinephrine, epinephrine, phenylephrine, isoproterenol and terbutaline alone or in combination with various concentrations of the inhibitors, phenoxybenzamine, piperoxan and propranolol, were used to analyze adrenoceptors in strips from the protruding portion of the follicle. Such strips showed no appreciable spontaneous contractions. A contractile response was found to be mediated by alpha receptors. The KA value for norepinephrine (determined in combination with phenoxybenzamine) was found to be 2.26 X 10- minus 6 M and KB for piperoxan (determined in combination with norepinephrine) was 1.02 X 10-minus 8 M (pA2 = 8.19). Adrenergic beta receptors mediated relaxation of the strips, and the KB value for propranolol (determined in combination with terbutaline) was 7.28 X 10-minus 9 M (pA2 = 8.17)."}
{"id": "PMID:238022", "title": "Biochemical and histofluorescence studies of catecholamines in superior cervical ganglia in organ culture.", "content": "The metabolism of catecholamines in rat superior cervical ganglia in organ culture was examined by biochemical and histofluorescence methods. Pronounced increases in both norepinephrine and dopamine content were observed in the cultured ganglia. Norepinephrine levels were more than doubled after 12 hours in culture and reached a maximum after 24 hours. The greatest increase in norepinephrine concentration occurred in the region of the postganglionic nerve trunks and was correlated with an accumulation of intense catecholamine fluorescence in the stumps of the severed postganglionic nerves. Since the rate of norepinephrine synthesis was unaltered, the increase in norepinephrine levels in cultured ganglia appears to be a result of blocked axoplasmic transport of this amine out of the ganglia. The dopamine content of the cultured preparations was not altered after 24 hours but increased rapidly thereafter and attained a maximum at 48 hours. The changes in dopamine did not parallel the changes in norepinephrine either in time course or distribution. The elevated levels of dopamine were accompanied by an increased rate of dopamine synthesis. It is suggested that the increased dopamine content in cultured ganglia is the result of an enhanced synthesis of this amine by specific dopaminergic cells.", "contents": "Biochemical and histofluorescence studies of catecholamines in superior cervical ganglia in organ culture. The metabolism of catecholamines in rat superior cervical ganglia in organ culture was examined by biochemical and histofluorescence methods. Pronounced increases in both norepinephrine and dopamine content were observed in the cultured ganglia. Norepinephrine levels were more than doubled after 12 hours in culture and reached a maximum after 24 hours. The greatest increase in norepinephrine concentration occurred in the region of the postganglionic nerve trunks and was correlated with an accumulation of intense catecholamine fluorescence in the stumps of the severed postganglionic nerves. Since the rate of norepinephrine synthesis was unaltered, the increase in norepinephrine levels in cultured ganglia appears to be a result of blocked axoplasmic transport of this amine out of the ganglia. The dopamine content of the cultured preparations was not altered after 24 hours but increased rapidly thereafter and attained a maximum at 48 hours. The changes in dopamine did not parallel the changes in norepinephrine either in time course or distribution. The elevated levels of dopamine were accompanied by an increased rate of dopamine synthesis. It is suggested that the increased dopamine content in cultured ganglia is the result of an enhanced synthesis of this amine by specific dopaminergic cells."}
{"id": "PMID:238023", "title": "Biochemical and functional evaluation of the sympathectomy produced by the administration of guanethidine to newborn rats.", "content": "The administration of guanethidine to newborn rats has been shown by morphological criteria to destroy sympathetic neurons. Newborn rats were injected with guanethidine (50-100 mg/kg/day for 20 days). Upon maturation (at 10 weeks old), the degree of destruction of the sympathetic nervous system (sympathectomy) was assessed. Marked decreases (80-98%) in the norepinephrine concentration in several tissues (heart, spleen, intestine, mesentery, kidney, uterus, vas deferens) were observed in the guanethidine-treated rats when compared to saline-treated controls. No changes were observed in the epinephrine concentration in the adrenals or in the norepinephrine levels in whole brain. Analysis of brain areas showed no change in the norepinephrine levels in brain stem and cerebrum and a small (18%) decrease in the cerebellum. Stimulation of the sympathetic vasomotor outflow in the pithed rat preparation produced almost no response in guanethidine-treated animals. Periarterial nerve stimulation of the isolated perfused kidney preparation also produced essentially no response in guanethidine-treated animals. Isolated intestinal preparations from guanethidine-treated animals responded to nerve stimulation with contractions rather than relaxation as seen in preparations from control animals. Isolated vas deferens preparations responded normally to nerve stimulation despite a 95% decrease in tissue norepinephrine concentration. These data indicate that administration of guanethidine to newborn rats produces a more complete peripheral sympathectomy, especially of the vasculature, than immunosympathectomy or neonatal administration of 6-hydroxydopamine and does so with no significant effect on central noradrenergic neurons.", "contents": "Biochemical and functional evaluation of the sympathectomy produced by the administration of guanethidine to newborn rats. The administration of guanethidine to newborn rats has been shown by morphological criteria to destroy sympathetic neurons. Newborn rats were injected with guanethidine (50-100 mg/kg/day for 20 days). Upon maturation (at 10 weeks old), the degree of destruction of the sympathetic nervous system (sympathectomy) was assessed. Marked decreases (80-98%) in the norepinephrine concentration in several tissues (heart, spleen, intestine, mesentery, kidney, uterus, vas deferens) were observed in the guanethidine-treated rats when compared to saline-treated controls. No changes were observed in the epinephrine concentration in the adrenals or in the norepinephrine levels in whole brain. Analysis of brain areas showed no change in the norepinephrine levels in brain stem and cerebrum and a small (18%) decrease in the cerebellum. Stimulation of the sympathetic vasomotor outflow in the pithed rat preparation produced almost no response in guanethidine-treated animals. Periarterial nerve stimulation of the isolated perfused kidney preparation also produced essentially no response in guanethidine-treated animals. Isolated intestinal preparations from guanethidine-treated animals responded to nerve stimulation with contractions rather than relaxation as seen in preparations from control animals. Isolated vas deferens preparations responded normally to nerve stimulation despite a 95% decrease in tissue norepinephrine concentration. These data indicate that administration of guanethidine to newborn rats produces a more complete peripheral sympathectomy, especially of the vasculature, than immunosympathectomy or neonatal administration of 6-hydroxydopamine and does so with no significant effect on central noradrenergic neurons."}
{"id": "PMID:238024", "title": "Time course of the effect of reserpine administration on tyrosine hydroxylase activity in adrenal glands and vasa deferentia.", "content": "During the first several hours after administration of reserpine, tyrosine hydroxylase activity in rat adrenal slices and in isolated intact vasa deferentia of mice and rats is profoundly reduced, although no effect on enzyme activity in isolated fortified homogenates of these tissues is demonstrable. This effect, observed only in intact preparations, is competitively antagonized by addition to the medium of the synthetic pterin cofactor, 6,7-dimethyltetrahydropterin (DMPH4). Kinetic analysis of the effect of acute reserpine treatment on tyrosine hydroxylase activity in these isolated, intact tissues indicates that the Km for the pterin cofactor is increased but the Vmax is not altered. The results indicate that reserpine produces its inhibition of tyrosine hydroxylase by preventing catecholamine storage and causing elevated levels of free intraneuronal norepinephrine. The catecholamine inhibits the enzyme in a manner which is competitive with the pterin cofactor. After more chronic reserpine treatment, when catecholamine stores are severly depleted, this inhibition of tyrosine hydroxylase activity in intact tissues is no longer apparent. After 3 days of treatment, increased levels of tyrosine hydroxylase are demonstrable in the adrenal glands of rats but not in the vass deferentia of either mice or rats. The increased enzyme levels in the adrenal gland are presumably due to increased enzyme formation.", "contents": "Time course of the effect of reserpine administration on tyrosine hydroxylase activity in adrenal glands and vasa deferentia. During the first several hours after administration of reserpine, tyrosine hydroxylase activity in rat adrenal slices and in isolated intact vasa deferentia of mice and rats is profoundly reduced, although no effect on enzyme activity in isolated fortified homogenates of these tissues is demonstrable. This effect, observed only in intact preparations, is competitively antagonized by addition to the medium of the synthetic pterin cofactor, 6,7-dimethyltetrahydropterin (DMPH4). Kinetic analysis of the effect of acute reserpine treatment on tyrosine hydroxylase activity in these isolated, intact tissues indicates that the Km for the pterin cofactor is increased but the Vmax is not altered. The results indicate that reserpine produces its inhibition of tyrosine hydroxylase by preventing catecholamine storage and causing elevated levels of free intraneuronal norepinephrine. The catecholamine inhibits the enzyme in a manner which is competitive with the pterin cofactor. After more chronic reserpine treatment, when catecholamine stores are severly depleted, this inhibition of tyrosine hydroxylase activity in intact tissues is no longer apparent. After 3 days of treatment, increased levels of tyrosine hydroxylase are demonstrable in the adrenal glands of rats but not in the vass deferentia of either mice or rats. The increased enzyme levels in the adrenal gland are presumably due to increased enzyme formation."}
{"id": "PMID:238025", "title": "Stimulation of adenosine 3',5'-monophosphate formation in rat cerebral cortical slices by methoxamine: interaction with an alpha adrenergic receptor.", "content": "Methoxamine elicits a rapid accumulation of adenosine 3',5'-monophosphate (cyclic AMP) in rat cerebral cortical slices with maximal effects at 100 muM. The accumulations of cyclic AMP elicited by this amine are completely blocked by the alpha adrenergic antagonists, phenoxybenzamine and dihydroergokryptine, partially blocked by the alpha antagonist, phentolamine, and unaffected by the beta blocking agent, propranolol, or by the local anesthetic, tetracaine. The magnitude of the accumulations of cyclic AMP elicited by methoxamine in cerebral cortical slices of four rat strains (F-344, ACI, BUF, and Sprague-Dawley) exhibit a strong negative correlation with spontaneous motor activity and a positive correlation with the magnitude of norepinephrine-elicited accumulations of cyclic AMP. The stimulatory interaction of methoxamine with alpha adrenergically regulated cyclic AMP-generating systems differs from the interaction of norepinephrine with alpha receptors as evidenced by the following observations: 1) the stimulatory effects of methoxamine and norepinephrine are nearly additive; 2) the stimulatory effects of methoxamine and adenosine are nearly additive, whereas the effects of norepinephrine and adenosine are much more than additive. Methoxamine, however, does not increase further the magnitude of accumulation of cyclic AMP elicited by a combination of norepinephrine and adenosine. The results are consonant with the interaction of methoxamine with alpha adrenergic receptors which are normally activated by norepinephrine only to a marginal extent. However, in the presence of adenosine, these receptors are now sensitive to activation by norepinephrine.", "contents": "Stimulation of adenosine 3',5'-monophosphate formation in rat cerebral cortical slices by methoxamine: interaction with an alpha adrenergic receptor. Methoxamine elicits a rapid accumulation of adenosine 3',5'-monophosphate (cyclic AMP) in rat cerebral cortical slices with maximal effects at 100 muM. The accumulations of cyclic AMP elicited by this amine are completely blocked by the alpha adrenergic antagonists, phenoxybenzamine and dihydroergokryptine, partially blocked by the alpha antagonist, phentolamine, and unaffected by the beta blocking agent, propranolol, or by the local anesthetic, tetracaine. The magnitude of the accumulations of cyclic AMP elicited by methoxamine in cerebral cortical slices of four rat strains (F-344, ACI, BUF, and Sprague-Dawley) exhibit a strong negative correlation with spontaneous motor activity and a positive correlation with the magnitude of norepinephrine-elicited accumulations of cyclic AMP. The stimulatory interaction of methoxamine with alpha adrenergically regulated cyclic AMP-generating systems differs from the interaction of norepinephrine with alpha receptors as evidenced by the following observations: 1) the stimulatory effects of methoxamine and norepinephrine are nearly additive; 2) the stimulatory effects of methoxamine and adenosine are nearly additive, whereas the effects of norepinephrine and adenosine are much more than additive. Methoxamine, however, does not increase further the magnitude of accumulation of cyclic AMP elicited by a combination of norepinephrine and adenosine. The results are consonant with the interaction of methoxamine with alpha adrenergic receptors which are normally activated by norepinephrine only to a marginal extent. However, in the presence of adenosine, these receptors are now sensitive to activation by norepinephrine."}
{"id": "PMID:238026", "title": "Effect of the H2-receptor antagonists (burimamide and metiamide) on gastric secretion stimulated by histamine and its methyl derivatives.", "content": "This study was done to determine the comparative effectiveness of burimamide and metiamide as antagonists of gastric secretion stimulated by histamine and its methyl derivatives, Nalpha-methylhistamine, N-alpha,N-alpha-dimethylhistamine and 4-methylhistamine, in dogs with vagally denervated (Heidenhain pouches) and vagally innervated gastric mucosal septal pouches (Pavlov-type pouches). The secretagogues were always given by continuous i.v. infusion to produce steady states of secretory activity in the fasted conscious dogs; the antagonists were given by either rapid \"bolus\" i.v. injection or continuous i.v. infusion. With bolus injections, both antagonists promptly inhibited the secretion produced by histamine and its methyl derivatives. When control secretory rates were similar, 40 mumol of burimamide per kg and 4 mumol of metiamide per kg produced the same degree of inhibition. When the antagonists were also given by continuous i.v. infusion, the difference between them was greater, metiamide being 15 to 17 times more potent than burimamide. The effectiveness of the antagonists was not changed by vagal denervation. Symptoms of toxicity to burimamide developed at doses in excess of 30 mumol/kg/hr; none occurred with doses of metiamide ranging from 1.8 to 7.5 mumol/kg/hr.", "contents": "Effect of the H2-receptor antagonists (burimamide and metiamide) on gastric secretion stimulated by histamine and its methyl derivatives. This study was done to determine the comparative effectiveness of burimamide and metiamide as antagonists of gastric secretion stimulated by histamine and its methyl derivatives, Nalpha-methylhistamine, N-alpha,N-alpha-dimethylhistamine and 4-methylhistamine, in dogs with vagally denervated (Heidenhain pouches) and vagally innervated gastric mucosal septal pouches (Pavlov-type pouches). The secretagogues were always given by continuous i.v. infusion to produce steady states of secretory activity in the fasted conscious dogs; the antagonists were given by either rapid \"bolus\" i.v. injection or continuous i.v. infusion. With bolus injections, both antagonists promptly inhibited the secretion produced by histamine and its methyl derivatives. When control secretory rates were similar, 40 mumol of burimamide per kg and 4 mumol of metiamide per kg produced the same degree of inhibition. When the antagonists were also given by continuous i.v. infusion, the difference between them was greater, metiamide being 15 to 17 times more potent than burimamide. The effectiveness of the antagonists was not changed by vagal denervation. Symptoms of toxicity to burimamide developed at doses in excess of 30 mumol/kg/hr; none occurred with doses of metiamide ranging from 1.8 to 7.5 mumol/kg/hr."}
{"id": "PMID:238027", "title": "4-Nitrocatechol production from rho-nitrophenol by rat liver.", "content": "Time course studies of rho-nitroanisole O-demethylation revealed formaldehyde production in excess of rho-nitrophenol (PNP) and 4-nitrocatechol (NTC) formation by rat liver microsomes. This indicated that these products (PNP, NTC) were metabolised further. The hydroxylation reaction PNP yields NTC showed substrate and product inhibition and a requirement for reduced nicotinamide adenine dinucleotide phosphate and O2 and was localized in liver microsomes. It was strongly activated by ascorbic acid, cysteine, adenosine triphosphate or hydroxylamine in vitro and enhanced by phenobarbital treatment in vivo. Mercapturic derivatives were metabolized to the corresponding hydroxy compounds with the same speed as their parent compounds. Both PNP and NTC were metabolized to the corresponding glucuronide and sulfate conjugates. On the other hand, the PNP or NTC glucuronides and sulfates were metabolized with liver microsomes to PNP and NTC.", "contents": "4-Nitrocatechol production from rho-nitrophenol by rat liver. Time course studies of rho-nitroanisole O-demethylation revealed formaldehyde production in excess of rho-nitrophenol (PNP) and 4-nitrocatechol (NTC) formation by rat liver microsomes. This indicated that these products (PNP, NTC) were metabolised further. The hydroxylation reaction PNP yields NTC showed substrate and product inhibition and a requirement for reduced nicotinamide adenine dinucleotide phosphate and O2 and was localized in liver microsomes. It was strongly activated by ascorbic acid, cysteine, adenosine triphosphate or hydroxylamine in vitro and enhanced by phenobarbital treatment in vivo. Mercapturic derivatives were metabolized to the corresponding hydroxy compounds with the same speed as their parent compounds. Both PNP and NTC were metabolized to the corresponding glucuronide and sulfate conjugates. On the other hand, the PNP or NTC glucuronides and sulfates were metabolized with liver microsomes to PNP and NTC."}
{"id": "PMID:238028", "title": "Rate-dependent Effects of drugs. II. effects of some major tranquilizers on multiple fixed-ratio, fixed-interval schedule performance.", "content": "The effects of promazine, chlorpromazine, triflupromazine, prochlorperazine, trifluoperazine, perphenazine, fluphenazine, haloperidol, benzquinamide, tetrabenazine and chlorprothixene were determined on the rate of conditioned key pecking of pigeons under a multiple fixed-ratio 30, fixed-interval 5-minute schedule of food presentation. Chlorpromazine, prochlorperazine, perphenazine, chlorprothixene and tetrabenazine decreased responding relatively more within the fixed-interval component than within the fixed-ratio component and also produced rate-dependent effects within the fixed interval component, increasing the low rates of responding early in the fixed-interval but decreasing the high rates of responding in the terminal parts of the fixed interval. Triflupromazine, trifluoperazine, fluphenazine and haloperidol also decreased responding relatively more within the fixed-interval component than within the fixed-ratio component, but did not produce rate-dependent effects within the fixed-interval component. Both low and high rates of responding within the fixed interval were decreased only by these four drugs and they produced small and inconsistent decreases in the quarter-life values. Promazine and benzquinamide decreased responding relatively more within the fixed-ratio component than within the fixed-interval component and also produced rate-dependent effects within the fixed-interval component. There was a structure-activity relationship between the chemical group on the benzene ring of the phenothiazine nucleus and the rate-dependent effect on responding within the fixed-interval component. Phenothiazines with a hydrogen or chlorine group on the benzene ring produced a rate-dependent effect on responding within the fixed interval, while phenothiazines with a trifluoromethyl group on the benzene ring did not produce a rate-dependent effect on responding within the fixed interval.", "contents": "Rate-dependent Effects of drugs. II. effects of some major tranquilizers on multiple fixed-ratio, fixed-interval schedule performance. The effects of promazine, chlorpromazine, triflupromazine, prochlorperazine, trifluoperazine, perphenazine, fluphenazine, haloperidol, benzquinamide, tetrabenazine and chlorprothixene were determined on the rate of conditioned key pecking of pigeons under a multiple fixed-ratio 30, fixed-interval 5-minute schedule of food presentation. Chlorpromazine, prochlorperazine, perphenazine, chlorprothixene and tetrabenazine decreased responding relatively more within the fixed-interval component than within the fixed-ratio component and also produced rate-dependent effects within the fixed interval component, increasing the low rates of responding early in the fixed-interval but decreasing the high rates of responding in the terminal parts of the fixed interval. Triflupromazine, trifluoperazine, fluphenazine and haloperidol also decreased responding relatively more within the fixed-interval component than within the fixed-ratio component, but did not produce rate-dependent effects within the fixed-interval component. Both low and high rates of responding within the fixed interval were decreased only by these four drugs and they produced small and inconsistent decreases in the quarter-life values. Promazine and benzquinamide decreased responding relatively more within the fixed-ratio component than within the fixed-interval component and also produced rate-dependent effects within the fixed-interval component. There was a structure-activity relationship between the chemical group on the benzene ring of the phenothiazine nucleus and the rate-dependent effect on responding within the fixed-interval component. Phenothiazines with a hydrogen or chlorine group on the benzene ring produced a rate-dependent effect on responding within the fixed interval, while phenothiazines with a trifluoromethyl group on the benzene ring did not produce a rate-dependent effect on responding within the fixed interval."}
{"id": "PMID:238029", "title": "Acidification in the rat proximal jejunum.", "content": "1. Production of hydrogen ions by the rat proximal jejunum was investigated using the everted sac technique. 2. Acidification occurred in the absence of glucose, increasing on addition of glucose to reach a maximal value. An apparent Km of 1-78 mM was derived for the glucose-dependent process. 3. Acidification in the presence of glucose was inhibited by 10 mM-2:4-dinitrophenol, 10 mM phlorrhizin, 10 mM aminophylline and anaerobiosis. 4. Histamine, ethylenediamine tetraacetic acid (EDTA), ouabain and acetazolamide, compounds known to alter acid production in gastric mucosa had no effect on jejunal acidification. 5. Galactose and 3-O-methylglucose failed to increase acidification; in contrast, mannose and fructose did lead to increases, indicating metabolic origin of the hydrogen ions. 6. Serosal and mucosal lactate production were measured and the calculated percentage of hydrogen ions possibly derived from this source was shown to account for only a small proportion of acidification. 7. The greatest increase in acidification with minimal simultaneous production of lactate occurred with ATP which was shown not to enter intestinal tissues. 8. A hypothesis for acidification, that of the break-down at the mucosal surface of ATP from intracellular metabolic sources, is proposed and its relevance to the postulated microclimate is discussed.", "contents": "Acidification in the rat proximal jejunum. 1. Production of hydrogen ions by the rat proximal jejunum was investigated using the everted sac technique. 2. Acidification occurred in the absence of glucose, increasing on addition of glucose to reach a maximal value. An apparent Km of 1-78 mM was derived for the glucose-dependent process. 3. Acidification in the presence of glucose was inhibited by 10 mM-2:4-dinitrophenol, 10 mM phlorrhizin, 10 mM aminophylline and anaerobiosis. 4. Histamine, ethylenediamine tetraacetic acid (EDTA), ouabain and acetazolamide, compounds known to alter acid production in gastric mucosa had no effect on jejunal acidification. 5. Galactose and 3-O-methylglucose failed to increase acidification; in contrast, mannose and fructose did lead to increases, indicating metabolic origin of the hydrogen ions. 6. Serosal and mucosal lactate production were measured and the calculated percentage of hydrogen ions possibly derived from this source was shown to account for only a small proportion of acidification. 7. The greatest increase in acidification with minimal simultaneous production of lactate occurred with ATP which was shown not to enter intestinal tissues. 8. A hypothesis for acidification, that of the break-down at the mucosal surface of ATP from intracellular metabolic sources, is proposed and its relevance to the postulated microclimate is discussed."}
{"id": "PMID:238033", "title": "Effects of potassium, veratridine, and scorpion venom on calcium accumulation and transmitter release by nerve terminals in vitro.", "content": "1. 45-Ca uptake by pinched-off nerve terminals (synaptosomes) of rat brain incubated in standard physiological saline (including 132 mM-Na + 5mM-K + 1-2 mM-Ca) at 30 degrees C averages about 0-5 mumole Ca per g protein per minute. This may be equivalent to a Ca influx of about 0-03 p-mole/cm-2 sec. 2. The rate of 45-Ca uptake is increased when the concentration of K in the medium is increased above 15-20 mM, K replacing Na isosmotically. Maximum stimulation, a three- to six-fold increase in the rate of Ca uptake, occurs when [K]o is about 60 mM. The effect of increased [K]o is reversible. 3. The K-stimulated Ca uptake is associated primarily with the nerve terminal fraction of brain homogenates. The entering Ca is not accompanied by extracellular markers such as mannitol or inulin. Replacement of external chloride by methylsulphate or sulphate does not prevent the stimulation by K. 4. The effects of external K are quantitatively mimicked by Rb. Caesium also stimulates Ca uptake, but is only about one fifth as effective as K or Rb; Li is ineffective. 5. Two other depolarizing agents also stimulate Ca uptake by synaptosomes: veratridine (7-5 times 10- minus 6 to 7-5 times 10- minus 5 M) and scorpion (Leirus quinquestriatus) venom (6-7 times 10- minus 7 to 6-7 times 10- minus g/ml.). The stimulatory effects of veratridine and scorpion venom, but not of increased [K] are blocked by 2 times 10- minus 7 M tetrodotoxin. 6. Internal K also influences the rate of 45-Ca uptake by synaptosomes: lowering [K]i reduces the stimulatory effect of external K and veratridine. 7. Replacement of external Na by choline markedly inhibits the response to veratridine, but has a much smaller effect on the response to increased [K]o. 8. The Ca uptake mechanism has an apparent dissociation constant for Ca (KCa) of about 0-8 mM. Increasing [K]o increases the maximal rate of Ca uptake, but has no effect on KCa. The K-induced 45-Ca uptake is competitively inhibited by Mg-2+, Mn-2+ and La-3+. 9. The release of acetylcholine and noradrenaline was also studied. Increasing [K]o stimulates external Ca-dependent acetylcholine release. Scorpion venom stimulates noradrenaline release from synaptosomes; this effect could be prevented by adding tetrodotoxin or removing external Ca. 10. These results indicate that synaptosomes may increase their permeability to Ca, accumulate Ca and release neural transmitter substances, when stimulated by depolarizing agents under appropriate physiological conditions.", "contents": "Effects of potassium, veratridine, and scorpion venom on calcium accumulation and transmitter release by nerve terminals in vitro. 1. 45-Ca uptake by pinched-off nerve terminals (synaptosomes) of rat brain incubated in standard physiological saline (including 132 mM-Na + 5mM-K + 1-2 mM-Ca) at 30 degrees C averages about 0-5 mumole Ca per g protein per minute. This may be equivalent to a Ca influx of about 0-03 p-mole/cm-2 sec. 2. The rate of 45-Ca uptake is increased when the concentration of K in the medium is increased above 15-20 mM, K replacing Na isosmotically. Maximum stimulation, a three- to six-fold increase in the rate of Ca uptake, occurs when [K]o is about 60 mM. The effect of increased [K]o is reversible. 3. The K-stimulated Ca uptake is associated primarily with the nerve terminal fraction of brain homogenates. The entering Ca is not accompanied by extracellular markers such as mannitol or inulin. Replacement of external chloride by methylsulphate or sulphate does not prevent the stimulation by K. 4. The effects of external K are quantitatively mimicked by Rb. Caesium also stimulates Ca uptake, but is only about one fifth as effective as K or Rb; Li is ineffective. 5. Two other depolarizing agents also stimulate Ca uptake by synaptosomes: veratridine (7-5 times 10- minus 6 to 7-5 times 10- minus 5 M) and scorpion (Leirus quinquestriatus) venom (6-7 times 10- minus 7 to 6-7 times 10- minus g/ml.). The stimulatory effects of veratridine and scorpion venom, but not of increased [K] are blocked by 2 times 10- minus 7 M tetrodotoxin. 6. Internal K also influences the rate of 45-Ca uptake by synaptosomes: lowering [K]i reduces the stimulatory effect of external K and veratridine. 7. Replacement of external Na by choline markedly inhibits the response to veratridine, but has a much smaller effect on the response to increased [K]o. 8. The Ca uptake mechanism has an apparent dissociation constant for Ca (KCa) of about 0-8 mM. Increasing [K]o increases the maximal rate of Ca uptake, but has no effect on KCa. The K-induced 45-Ca uptake is competitively inhibited by Mg-2+, Mn-2+ and La-3+. 9. The release of acetylcholine and noradrenaline was also studied. Increasing [K]o stimulates external Ca-dependent acetylcholine release. Scorpion venom stimulates noradrenaline release from synaptosomes; this effect could be prevented by adding tetrodotoxin or removing external Ca. 10. These results indicate that synaptosomes may increase their permeability to Ca, accumulate Ca and release neural transmitter substances, when stimulated by depolarizing agents under appropriate physiological conditions."}
{"id": "PMID:238034", "title": "The influence of sodium on calcium fluxes in pinched-off nerve terminals in vitro.", "content": "1. The influence of internal and external Na concentrations on Ca movements have been measured in pinch-off presynaptic nerve terminals (synaptosomes). Ca uptake is enhanced when external Na (Nao) is replaced by Li, choline or dextrose, in Na-loaded synaptosomes. Depletion of internal Na (Nai) abolishes the stimulatory effect of external Na removal. 2. Ca uptake from Na-depleted media is proportional to [Na]i -2, and averages about 1-5 mumole Ca/g synaptosome protein per minute when [Na]i is approximately 137 mM. This may correspond to a Ca influx of about 0-1 p-mole/cm-2 sec. 3. External Na is a competitive inhibitor of the Nai-dependent Ca uptake. The interrelationship between [Na]o, [Ca]o and Ca uptake indicate that two external Na ions may compete with one Ca at each uptake site. 4. The distribution of particles with Nai-dependent Ca uptake activity parallels the distribution of synaptosomes in the preparative sucrose gradient. Thus, this Ca uptake activity is probably a property of the pinched-off nerve terminals per se, and not of the mitochondria which may contaminate the synaptosome fraction. 5. The Nai-dependent Ca uptake mechanism requires an intact surface membrane, since synaptosomes subjected to osmotic lysis lose the ability to accumulate Ca by this route. 6. Ca efflux into Ca-free media is largely dependent upon the presence of external Na. The curve relating Ca efflux to [Na]o is sigmoid, and suggests that more than one external Na ion (perhaps 2 or 3) is needed to activate the efflux of each Ca ion. 7. The net Ca gain exhibited by Na-loaded synaptosomes incubated in Na-depleted media can be accounted for by the increased Ca uptake and decreased Ca loss observed under these conditions. 8. Treatment of synaptosomes with cyanide or 2,4-dinitrophenol decreases Ca uptake and enhances Ca efflux into Na-containing media. This results in a net loss of Ca from the terminals, even in the presence of external Ca. 9. In contrast to the Ca efflux from synaptosomes, the Ca efflux from brain mitochondria is not dependent upon external Na, and is reduced by succinate, a substrate which is known to fuel mitochondrial respiration. 10. The temperature coefficient (Q10) of the Nai-dependent Ca uptake is about 3. 11. The Nai-dependent Ca uptake is reduced at low pH. The relationship between this Ca uptake and pH approximates a titration curve with a pKa of about 5-6. 12. The data indicate that Ca transport in rat brain presynaptic terminals may involve a carrier-mediated Na-Ca exchange mechanism, and that some of the energy required for Ca extrusion may come from the Na electrochemical gradient across the surface membranes.", "contents": "The influence of sodium on calcium fluxes in pinched-off nerve terminals in vitro. 1. The influence of internal and external Na concentrations on Ca movements have been measured in pinch-off presynaptic nerve terminals (synaptosomes). Ca uptake is enhanced when external Na (Nao) is replaced by Li, choline or dextrose, in Na-loaded synaptosomes. Depletion of internal Na (Nai) abolishes the stimulatory effect of external Na removal. 2. Ca uptake from Na-depleted media is proportional to [Na]i -2, and averages about 1-5 mumole Ca/g synaptosome protein per minute when [Na]i is approximately 137 mM. This may correspond to a Ca influx of about 0-1 p-mole/cm-2 sec. 3. External Na is a competitive inhibitor of the Nai-dependent Ca uptake. The interrelationship between [Na]o, [Ca]o and Ca uptake indicate that two external Na ions may compete with one Ca at each uptake site. 4. The distribution of particles with Nai-dependent Ca uptake activity parallels the distribution of synaptosomes in the preparative sucrose gradient. Thus, this Ca uptake activity is probably a property of the pinched-off nerve terminals per se, and not of the mitochondria which may contaminate the synaptosome fraction. 5. The Nai-dependent Ca uptake mechanism requires an intact surface membrane, since synaptosomes subjected to osmotic lysis lose the ability to accumulate Ca by this route. 6. Ca efflux into Ca-free media is largely dependent upon the presence of external Na. The curve relating Ca efflux to [Na]o is sigmoid, and suggests that more than one external Na ion (perhaps 2 or 3) is needed to activate the efflux of each Ca ion. 7. The net Ca gain exhibited by Na-loaded synaptosomes incubated in Na-depleted media can be accounted for by the increased Ca uptake and decreased Ca loss observed under these conditions. 8. Treatment of synaptosomes with cyanide or 2,4-dinitrophenol decreases Ca uptake and enhances Ca efflux into Na-containing media. This results in a net loss of Ca from the terminals, even in the presence of external Ca. 9. In contrast to the Ca efflux from synaptosomes, the Ca efflux from brain mitochondria is not dependent upon external Na, and is reduced by succinate, a substrate which is known to fuel mitochondrial respiration. 10. The temperature coefficient (Q10) of the Nai-dependent Ca uptake is about 3. 11. The Nai-dependent Ca uptake is reduced at low pH. The relationship between this Ca uptake and pH approximates a titration curve with a pKa of about 5-6. 12. The data indicate that Ca transport in rat brain presynaptic terminals may involve a carrier-mediated Na-Ca exchange mechanism, and that some of the energy required for Ca extrusion may come from the Na electrochemical gradient across the surface membranes."}
{"id": "PMID:238036", "title": "Preparation of a glycoprotein fraction from pooled human plasma and its evaluation as a substrate for the assay of Clostridium welchii (C. perfringens) neuraminidase.", "content": "A glycoprotein fraction (fraction VII) suitable for use as a substrate in assays of microbial neuraminidase was prepared from pooled human plasma. It is pasteurised during preparation to eliminate the risk of transmission of serum hepatitis. This results in polymerisation of some of the gamma1-acid glycoprotein, but fraction VII is shown to be an excellent substrate for the neuraminidase of Clostridium welchii (C. perfringens). A sensitive assay procedure is described. A number of factors may interfere with the measurement of NANA released by the action of microbial neuraminidase and procedures are described for evaluation of this problem. Fraction VII is easy to prepare, cheap and available in standard form in large amounts (inquiries should be addressed to J. K. S.); it is recommended for routine use as a convenient substrate for neuraminidase assays.", "contents": "Preparation of a glycoprotein fraction from pooled human plasma and its evaluation as a substrate for the assay of Clostridium welchii (C. perfringens) neuraminidase. A glycoprotein fraction (fraction VII) suitable for use as a substrate in assays of microbial neuraminidase was prepared from pooled human plasma. It is pasteurised during preparation to eliminate the risk of transmission of serum hepatitis. This results in polymerisation of some of the gamma1-acid glycoprotein, but fraction VII is shown to be an excellent substrate for the neuraminidase of Clostridium welchii (C. perfringens). A sensitive assay procedure is described. A number of factors may interfere with the measurement of NANA released by the action of microbial neuraminidase and procedures are described for evaluation of this problem. Fraction VII is easy to prepare, cheap and available in standard form in large amounts (inquiries should be addressed to J. K. S.); it is recommended for routine use as a convenient substrate for neuraminidase assays."}
{"id": "PMID:238037", "title": "A new selective medium for the isolation of Salmonellae other than Salmonella typhi.", "content": "A medium consisting of a MacConkey's base with added magnesium, calcium, cobalt, zinc, thiosulphate, novobiocin, iron dextran, Tween 80 and EDTA has been found highly selective for Salmonellaparatyphi B and most of the food poisoning salmonellae that commonly occur in Britain. Nearly all the normal faecal flora is inhibited.", "contents": "A new selective medium for the isolation of Salmonellae other than Salmonella typhi. A medium consisting of a MacConkey's base with added magnesium, calcium, cobalt, zinc, thiosulphate, novobiocin, iron dextran, Tween 80 and EDTA has been found highly selective for Salmonellaparatyphi B and most of the food poisoning salmonellae that commonly occur in Britain. Nearly all the normal faecal flora is inhibited."}
{"id": "PMID:238038", "title": "Standardisation of the nitroblue-tetrazolium test.", "content": "Optimal conditions for the NBT-reduction test have been sought. Increasing heparin concentrations up to 100 units per ml and a delay in performance of the test, especially when blood specimens are kept at room temperature, resulted in higher values for the NBT index, which then sometimes exceeded the upper limit of normal in healthy people and in uninfected patients. The effect of pH, composition of the buffer, and dye concentration was also investigated. Phosphate-buffered saline pH 7-2 containing 0-1% NBT dye, without glucose, gave the most reliable results. In endotoxin-stimulated NBT tests, the following procedure is recommended: incubation of 0-1 ml whole blood with lyophilised endotoxin 20 mug per ml. for 15 min. in a 37 degree C water bath, followed by the standard test with a 0-2% NBT solution. By this technique, the leucocyte reaction to various types of lipopolysaccharides was of the same order of magnitude. Drug therapy having an effect on blood components lowered this reaction, whatever the source of endotoxin used as stimulant. The importance of NBT-reduction tests is discussed. Standard conditions of test performance are strictly requisite if comparable results are to be obtained and if data not corresponding with the apparent clinical and other laboratory findings are to be evaluated correctly. The stimulated NBT test, performed in parallel with the standard test, is useful in the interpretation of abnormal results and in the detection of factors with a temporary or permanent effect on the phagocytic activity of pmn leucocytes.", "contents": "Standardisation of the nitroblue-tetrazolium test. Optimal conditions for the NBT-reduction test have been sought. Increasing heparin concentrations up to 100 units per ml and a delay in performance of the test, especially when blood specimens are kept at room temperature, resulted in higher values for the NBT index, which then sometimes exceeded the upper limit of normal in healthy people and in uninfected patients. The effect of pH, composition of the buffer, and dye concentration was also investigated. Phosphate-buffered saline pH 7-2 containing 0-1% NBT dye, without glucose, gave the most reliable results. In endotoxin-stimulated NBT tests, the following procedure is recommended: incubation of 0-1 ml whole blood with lyophilised endotoxin 20 mug per ml. for 15 min. in a 37 degree C water bath, followed by the standard test with a 0-2% NBT solution. By this technique, the leucocyte reaction to various types of lipopolysaccharides was of the same order of magnitude. Drug therapy having an effect on blood components lowered this reaction, whatever the source of endotoxin used as stimulant. The importance of NBT-reduction tests is discussed. Standard conditions of test performance are strictly requisite if comparable results are to be obtained and if data not corresponding with the apparent clinical and other laboratory findings are to be evaluated correctly. The stimulated NBT test, performed in parallel with the standard test, is useful in the interpretation of abnormal results and in the detection of factors with a temporary or permanent effect on the phagocytic activity of pmn leucocytes."}
{"id": "PMID:238046", "title": "A comparative evaluation of the treatment of typhoid fevers with co-trimoxazole and chloramphenicol in Egypt.", "content": "Seventy-two patients with bacteriologically proven enteric fever were treated with either co-trimoxazole (41 cases) or chloramphenicol (31 cases). C0-trimoxazole was found to be superior to chloramphenicol in relieving the toxaemia. The average number of days required for patients to become afebrile was 5-5 days in the co-trimoxazole group and 4-5 days in the chloramphenicol group. The cure rate was 97 per cent in each of the treatment groups. There occurred two relapses in the co-trimoxazole group and four relapses in the chloramphenicol group. No side effects of the co-trimoxazole were detected during the study. Co-trimoxazole can be considered as a good alternative to chloramphenicol in the treatment of the enteric fevers.", "contents": "A comparative evaluation of the treatment of typhoid fevers with co-trimoxazole and chloramphenicol in Egypt. Seventy-two patients with bacteriologically proven enteric fever were treated with either co-trimoxazole (41 cases) or chloramphenicol (31 cases). C0-trimoxazole was found to be superior to chloramphenicol in relieving the toxaemia. The average number of days required for patients to become afebrile was 5-5 days in the co-trimoxazole group and 4-5 days in the chloramphenicol group. The cure rate was 97 per cent in each of the treatment groups. There occurred two relapses in the co-trimoxazole group and four relapses in the chloramphenicol group. No side effects of the co-trimoxazole were detected during the study. Co-trimoxazole can be considered as a good alternative to chloramphenicol in the treatment of the enteric fevers."}
{"id": "PMID:238047", "title": "The undescended testis: management after puberty.", "content": "The patient seen after puberty with an intra-abdominal unilateral undescended testis should have orchiectomy. The patient seen after puberty and before the age of 50 years with unilateral undescended testis in the inguinal region should have orchiectomy because the risk of death from malignancy exceeds the risk of anesthesia and orchiectomy.", "contents": "The undescended testis: management after puberty. The patient seen after puberty with an intra-abdominal unilateral undescended testis should have orchiectomy. The patient seen after puberty and before the age of 50 years with unilateral undescended testis in the inguinal region should have orchiectomy because the risk of death from malignancy exceeds the risk of anesthesia and orchiectomy."}
{"id": "PMID:238048", "title": "Nitrofurantoin, sulfamethizole and cephalexin urinary concentration in unequally functioning pyelonephritic kidneys.", "content": "Nitrofurantoin, sulfamethizole and cephalexin peak urinary drug concentrations were studied in patients and non-human primates with unequally functioning pyelonephritic kidneys. The peak urinary drug concentration of the poorly functioning kidney in comparison to the better kidney was greater than its percentage relative blood flow or creatinine clearance but variable in its relationship to creatinine concentration, osmolality and sodium concentration. Although for each unit of creatinine clearance the poorly functioning kidney had a higher peak urinary drug concentration than the better functioning kidney, for each kidney the peak urinary drug concentration seemed to be directly proportional to the creatinine clearance, the drug dosage and the renal mechanisms of drug excretion. Nitrofurantoin in the usual recommended dosage did not reach minimal inhibitory urinary drug concentration below a unilateral creatinine clearance of 20 ml. per minute. Whereas, sulfamethizole and cephalexin reached peak urinary drug concentrations greater than the minimal inhibitory concentration at the lowest studied unilateral creatinine clearance of 4 and 11 ml. per minute, respectively.", "contents": "Nitrofurantoin, sulfamethizole and cephalexin urinary concentration in unequally functioning pyelonephritic kidneys. Nitrofurantoin, sulfamethizole and cephalexin peak urinary drug concentrations were studied in patients and non-human primates with unequally functioning pyelonephritic kidneys. The peak urinary drug concentration of the poorly functioning kidney in comparison to the better kidney was greater than its percentage relative blood flow or creatinine clearance but variable in its relationship to creatinine concentration, osmolality and sodium concentration. Although for each unit of creatinine clearance the poorly functioning kidney had a higher peak urinary drug concentration than the better functioning kidney, for each kidney the peak urinary drug concentration seemed to be directly proportional to the creatinine clearance, the drug dosage and the renal mechanisms of drug excretion. Nitrofurantoin in the usual recommended dosage did not reach minimal inhibitory urinary drug concentration below a unilateral creatinine clearance of 20 ml. per minute. Whereas, sulfamethizole and cephalexin reached peak urinary drug concentrations greater than the minimal inhibitory concentration at the lowest studied unilateral creatinine clearance of 4 and 11 ml. per minute, respectively."}
{"id": "PMID:238050", "title": "Serologic evidence of Venezuelan equine encephalitis in some wild and domestic populations of southern Texas.", "content": "More than 2,500 sera from approximately 30 wild and domestic species in southern Texas were tested for neutralizing antibodies to Venezuelan equine encephalitis (VEE). Virus isolations were also attempted from blood and tissue samples of many of the wild specimens. VEE neutralizing substances were present in a variety of species collected prior to the 1971 epizootic, suggesting that VEE was present and perhaps enzootic in this area before the recent epizootic. Serologic results of this study suggest that deer (Odocoileus virginianus) and feral swine (Sus scrofa) may serve as good indicators or sentinels of VEE transmission. The reservoir of VEE was not established, but results of the study suggest that a number of species or a combination of animal host populations including deer, feral swine, and peccaries (Pecari angulatus) may be involved in the eizootiologyof VEE in southern Texas.", "contents": "Serologic evidence of Venezuelan equine encephalitis in some wild and domestic populations of southern Texas. More than 2,500 sera from approximately 30 wild and domestic species in southern Texas were tested for neutralizing antibodies to Venezuelan equine encephalitis (VEE). Virus isolations were also attempted from blood and tissue samples of many of the wild specimens. VEE neutralizing substances were present in a variety of species collected prior to the 1971 epizootic, suggesting that VEE was present and perhaps enzootic in this area before the recent epizootic. Serologic results of this study suggest that deer (Odocoileus virginianus) and feral swine (Sus scrofa) may serve as good indicators or sentinels of VEE transmission. The reservoir of VEE was not established, but results of the study suggest that a number of species or a combination of animal host populations including deer, feral swine, and peccaries (Pecari angulatus) may be involved in the eizootiologyof VEE in southern Texas."}
{"id": "PMID:238051", "title": "Spontaneous peritonitis and systemic lupus erythematosus. Importance of accurate diagnosis of gram-positive bacterial infections.", "content": "Primary Gram-positive bacterial peritonitis developed in three patients with systemic lupus erythematosus (SLE). These cases suggest a possible association between these two entities. Furthermore, they emphasize the importance of accurate diagnosis when evaluating abdominal symptoms in patients with SLE.", "contents": "Spontaneous peritonitis and systemic lupus erythematosus. Importance of accurate diagnosis of gram-positive bacterial infections. Primary Gram-positive bacterial peritonitis developed in three patients with systemic lupus erythematosus (SLE). These cases suggest a possible association between these two entities. Furthermore, they emphasize the importance of accurate diagnosis when evaluating abdominal symptoms in patients with SLE."}
{"id": "PMID:238054", "title": "[Clinical course, diagnosis and treatment of idiopathic hypertrophic subaortic stenosis].", "content": "Clinical, ECG and X-ray data as well as catheterizational and angiographic data on 20 patients with idiopathic hypertrophic subaortic stenosis were analysed. The problems of medical and surgical treatment of the disease were discussed. The indications for surgical treatment were defined on the basis of the authors' surgical experience (5 operated on patients) and literature data.", "contents": "[Clinical course, diagnosis and treatment of idiopathic hypertrophic subaortic stenosis]. Clinical, ECG and X-ray data as well as catheterizational and angiographic data on 20 patients with idiopathic hypertrophic subaortic stenosis were analysed. The problems of medical and surgical treatment of the disease were discussed. The indications for surgical treatment were defined on the basis of the authors' surgical experience (5 operated on patients) and literature data."}
{"id": "PMID:238055", "title": "[Prognosis of the immediate outcome of myocardial infarct according to data of acid-base and blood oxygen balance].", "content": "In 261 patients with acute myocardial infarction an immediate prognosis of the disease was made by using quantitative values of the acid-base and blood oxygen balance, mathematically processed with the help of the analytical method of notion-shaping. The possibility of prognosing in priniciple on the ground of all the factors studied, the blood oxygen tension and the hemoglobin saturation with oxygen being the most informative, was ascertained.", "contents": "[Prognosis of the immediate outcome of myocardial infarct according to data of acid-base and blood oxygen balance]. In 261 patients with acute myocardial infarction an immediate prognosis of the disease was made by using quantitative values of the acid-base and blood oxygen balance, mathematically processed with the help of the analytical method of notion-shaping. The possibility of prognosing in priniciple on the ground of all the factors studied, the blood oxygen tension and the hemoglobin saturation with oxygen being the most informative, was ascertained."}
{"id": "PMID:238057", "title": "[Treatment of coronary shock].", "content": "A brief characteristics of the main therapeutic methods for shock in acute myocardial infarction cases is presented, including fast infusion of plasma-substitutes, noradrenalin, isoproterenol, alpha-adrenergic bocking agents, steroid hormones, intra-aortal balloon counter-pulsation, oxygen therapy, acidbase balance correction, etc. It is emphasized that proper therapy based on the evaluation of the nature of circulatory disorders in every particular case proves effective in some cases.", "contents": "[Treatment of coronary shock]. A brief characteristics of the main therapeutic methods for shock in acute myocardial infarction cases is presented, including fast infusion of plasma-substitutes, noradrenalin, isoproterenol, alpha-adrenergic bocking agents, steroid hormones, intra-aortal balloon counter-pulsation, oxygen therapy, acidbase balance correction, etc. It is emphasized that proper therapy based on the evaluation of the nature of circulatory disorders in every particular case proves effective in some cases."}
{"id": "PMID:238058", "title": "[Measurement of spontaneous platelet aggregation. Platelet aggregation test III (author's transl)].", "content": "A new measuring device for the estimation of the \"spontaneous\" aggregating activity of thrombocytes has been developed. In this photometric platelet aggregation test (PAT III) a small amount (0.6 ml) of platelet-rich plasma (PRP) is being rotated in a disc-shaped cuvette at 20 rpm, at 37% C. Changes in optical density of PRP which are induced by the formation of platelet aggregates are continuously registered using a chart recorder. The decisive trigger mechanism for aggregation is an increase of plasma pH in the rotating sample which is caused by evaporation of CO2. The results of the test depend on the platelet count in PRP. Aggregation curves are misrepresented by admixture of erythrocytes and lipid turbidity. The tendency of platelets to aggregate increases within 60-90 min following blood sampling. During this period the time interval to the onset of aggregation(Tr) is shortening, and the maximum aggregation speed (alpha2) is increasing. The spontaneously enhanced aggregation tendency of thrombocytes may be reliably measured from 60 min after drawing the blood. The reason for these time-dependent changes which are also demonstrable in ADP-collagen-or epinephrine-induced aggregation is probably the primary shape change of platelets, which occurs after blood drawing and makes them \"stickly\" and aggregable. PAT III was developed for the detection of enhanced platelet aggregation, indicating  a risk of thrombosis and thromboembolic omplications. The new measuring device  has been designed as \"universal\" aggregometer. Additional equipment is available for the registration of ADP-collagen-or epinephrine-induced aggregation similar to Born's and O'Brien's methods. The device may be mounted easily on an Eppendorf photometer without further modifications.", "contents": "[Measurement of spontaneous platelet aggregation. Platelet aggregation test III (author's transl)]. A new measuring device for the estimation of the \"spontaneous\" aggregating activity of thrombocytes has been developed. In this photometric platelet aggregation test (PAT III) a small amount (0.6 ml) of platelet-rich plasma (PRP) is being rotated in a disc-shaped cuvette at 20 rpm, at 37% C. Changes in optical density of PRP which are induced by the formation of platelet aggregates are continuously registered using a chart recorder. The decisive trigger mechanism for aggregation is an increase of plasma pH in the rotating sample which is caused by evaporation of CO2. The results of the test depend on the platelet count in PRP. Aggregation curves are misrepresented by admixture of erythrocytes and lipid turbidity. The tendency of platelets to aggregate increases within 60-90 min following blood sampling. During this period the time interval to the onset of aggregation(Tr) is shortening, and the maximum aggregation speed (alpha2) is increasing. The spontaneously enhanced aggregation tendency of thrombocytes may be reliably measured from 60 min after drawing the blood. The reason for these time-dependent changes which are also demonstrable in ADP-collagen-or epinephrine-induced aggregation is probably the primary shape change of platelets, which occurs after blood drawing and makes them \"stickly\" and aggregable. PAT III was developed for the detection of enhanced platelet aggregation, indicating  a risk of thrombosis and thromboembolic omplications. The new measuring device  has been designed as \"universal\" aggregometer. Additional equipment is available for the registration of ADP-collagen-or epinephrine-induced aggregation similar to Born's and O'Brien's methods. The device may be mounted easily on an Eppendorf photometer without further modifications."}
{"id": "PMID:238059", "title": "The effect of sampling technique on some blood parameters in the rat.", "content": "When used to restrain rats while obtaining cardiac blood, there was little difference between the effects of ether, pentobarbitone sodium, and fentanyl plus droperidol on acid-base balance, haemoglobin, haematocrit, plasma protein, calcium and magnesium. The use of manual restraint increased blood acidity, plasma protein, calcium and magnesium, but decreased blood glucose. Haemoglobin and haematocrit values were higher for tail blood than for blood removed from the heart or abdominal aorta.", "contents": "The effect of sampling technique on some blood parameters in the rat. When used to restrain rats while obtaining cardiac blood, there was little difference between the effects of ether, pentobarbitone sodium, and fentanyl plus droperidol on acid-base balance, haemoglobin, haematocrit, plasma protein, calcium and magnesium. The use of manual restraint increased blood acidity, plasma protein, calcium and magnesium, but decreased blood glucose. Haemoglobin and haematocrit values were higher for tail blood than for blood removed from the heart or abdominal aorta."}
{"id": "PMID:238060", "title": "The effect of sampling technique on acid-base balance and other blood parameters in the sheep.", "content": "The effect of 4 sampling routines--venipuncture, intravenous cannula, intravenous cannula following the administration of a tranquiliser (xylidino dihydrothiazine hydrochloride), intravenous cannula following exercise--were compared. Blood pH and base excess values were similar after venipuncture and cannula sampling, but higher (P less than 0 with 05) after the administration of the tranquiliser and lower (P less than 3 with 05) following exercise. Blood haemoglobin, haematocrit and lactate levels followed this pattern, while plasma protein levels were similar for all treatments except after exercise, where they were higher (P less than 0 with 05). The recovery of various blood parameters to normal values after a period of exercise was also studied: acid-base balance had returned to near normal within 60 min, while haemoglobin and haematocrit levels had returned to normal within 10 min.", "contents": "The effect of sampling technique on acid-base balance and other blood parameters in the sheep. The effect of 4 sampling routines--venipuncture, intravenous cannula, intravenous cannula following the administration of a tranquiliser (xylidino dihydrothiazine hydrochloride), intravenous cannula following exercise--were compared. Blood pH and base excess values were similar after venipuncture and cannula sampling, but higher (P less than 0 with 05) after the administration of the tranquiliser and lower (P less than 3 with 05) following exercise. Blood haemoglobin, haematocrit and lactate levels followed this pattern, while plasma protein levels were similar for all treatments except after exercise, where they were higher (P less than 0 with 05). The recovery of various blood parameters to normal values after a period of exercise was also studied: acid-base balance had returned to near normal within 60 min, while haemoglobin and haematocrit levels had returned to normal within 10 min."}
{"id": "PMID:238065", "title": "Self-evaluation of performance and the ability to discriminate blood alcohol concentrations.", "content": "Social drinkers who had been trained to discriminate their blood alcohol concentrations (BAC) tended to predict greater impairment of performance while drinking than did untrained controls, although their actual performance on coding tasks did not differ. It is suggested that training in BAC discrimination may enhance caution and concern about behavioral impairment while drinking.", "contents": "Self-evaluation of performance and the ability to discriminate blood alcohol concentrations. Social drinkers who had been trained to discriminate their blood alcohol concentrations (BAC) tended to predict greater impairment of performance while drinking than did untrained controls, although their actual performance on coding tasks did not differ. It is suggested that training in BAC discrimination may enhance caution and concern about behavioral impairment while drinking."}
{"id": "PMID:238066", "title": "Probability of arrest while driving under the influence of alcohol.", "content": "The probability of arrest while driving at a blood alcohol level over 0.10% was .0058 (about 1 in 200).", "contents": "Probability of arrest while driving under the influence of alcohol. The probability of arrest while driving at a blood alcohol level over 0.10% was .0058 (about 1 in 200)."}
{"id": "PMID:238067", "title": "Effects of alcohol on a Critical Tracking Task.", "content": "Performance on a Critical Tracking Task decreased significantly as blood alcohol levels increased.", "contents": "Effects of alcohol on a Critical Tracking Task. Performance on a Critical Tracking Task decreased significantly as blood alcohol levels increased."}
{"id": "PMID:238068", "title": "A self-administered Short Michigan Alcoholism Screening Test (SMAST).", "content": "The Michigan Alcoholism Screening Test and a shortened 13-item version can reliably be used as self-administered questionnaires.", "contents": "A self-administered Short Michigan Alcoholism Screening Test (SMAST). The Michigan Alcoholism Screening Test and a shortened 13-item version can reliably be used as self-administered questionnaires."}
{"id": "PMID:238069", "title": "Item analysis of the Michigan Alcoholism Screening Test.", "content": "The Michigan Alcoholism Screening Test was administered to 200 persons arrested for driving while intoxicated. Most items adequately discriminated between problem and nonproblem drinkers, but several questions assessing severe alcoholism symptoms did not consistenly differentiate between the 2 groups.", "contents": "Item analysis of the Michigan Alcoholism Screening Test. The Michigan Alcoholism Screening Test was administered to 200 persons arrested for driving while intoxicated. Most items adequately discriminated between problem and nonproblem drinkers, but several questions assessing severe alcoholism symptoms did not consistenly differentiate between the 2 groups."}
{"id": "PMID:238070", "title": "Multidisciplinary perspectives on alcoholism and the need for integration. An historical and prospective note.", "content": "The history of the recognition of alcoholism as a multidisciplinary social problem from the late 19th century through the evolution of the Center of Alcohol Studies is described, highlightning the men who brought the field prominence. The nature of alcoholism, viewed from an interdisciplinary perspective, is outluned.", "contents": "Multidisciplinary perspectives on alcoholism and the need for integration. An historical and prospective note. The history of the recognition of alcoholism as a multidisciplinary social problem from the late 19th century through the evolution of the Center of Alcohol Studies is described, highlightning the men who brought the field prominence. The nature of alcoholism, viewed from an interdisciplinary perspective, is outluned."}
{"id": "PMID:238071", "title": "Effects of ethanol and ethionine on DNA synthesis during experimental liver regeneration.", "content": "Ethanol reversed the ethionine-induced inhibition of 3H-thymidine incoroporation into hepatic DNA in the male and female rat after partial hepatectomy.", "contents": "Effects of ethanol and ethionine on DNA synthesis during experimental liver regeneration. Ethanol reversed the ethionine-induced inhibition of 3H-thymidine incoroporation into hepatic DNA in the male and female rat after partial hepatectomy."}
{"id": "PMID:238072", "title": "Control orientation in alcoholics related to extent of treatment.", "content": "The self-perceived locus of control of three groups of alcoholics who had had varying amounts of exposure to treatment was measured on the Internal-External (I-E) scale. Alcoholics who had had more treatment perceived themselves in greater control of their behavior in general and of their drinking in particualar than those who had had less treatment.", "contents": "Control orientation in alcoholics related to extent of treatment. The self-perceived locus of control of three groups of alcoholics who had had varying amounts of exposure to treatment was measured on the Internal-External (I-E) scale. Alcoholics who had had more treatment perceived themselves in greater control of their behavior in general and of their drinking in particualar than those who had had less treatment."}
{"id": "PMID:238073", "title": "Attempted suicide in alcoholics and drug addicts.", "content": "Alcoholics who had attempted suicide differed on several demographic variables from addicts to other drugs who had attempted suicide; however; they did not differ on any psychological variable.", "contents": "Attempted suicide in alcoholics and drug addicts. Alcoholics who had attempted suicide differed on several demographic variables from addicts to other drugs who had attempted suicide; however; they did not differ on any psychological variable."}
{"id": "PMID:238074", "title": "Alcoholism and abstinence among relatives of American Indian alcoholics.", "content": "The incidence of alcoholism among relatives of Indian alcoholics was significantly greater than it was among relatives of non-Indian alcoholics.", "contents": "Alcoholism and abstinence among relatives of American Indian alcoholics. The incidence of alcoholism among relatives of Indian alcoholics was significantly greater than it was among relatives of non-Indian alcoholics."}
{"id": "PMID:238076", "title": "DRL responding by rats during initial and prolonged alcohol administration.", "content": "Daily administration of alcohol did not affect the total response rate of rats on a DRL task although alcohol-treated animals made fewer correct (reinforced) responses than did controls.", "contents": "DRL responding by rats during initial and prolonged alcohol administration. Daily administration of alcohol did not affect the total response rate of rats on a DRL task although alcohol-treated animals made fewer correct (reinforced) responses than did controls."}
{"id": "PMID:238077", "title": "Adolescent development and the onset of drinking. A longitudinal study.", "content": "Junior and senior high-school students were studied over a 4-year period. The likelihood of drinking was directly related to the degree of transition- or problem-proneness, and a developmental relationship between onset of drinking and other socipsychological attributes was found. It is concluded that becoming a drinker is an integral aspect of the process of adolscent development.", "contents": "Adolescent development and the onset of drinking. A longitudinal study. Junior and senior high-school students were studied over a 4-year period. The likelihood of drinking was directly related to the degree of transition- or problem-proneness, and a developmental relationship between onset of drinking and other socipsychological attributes was found. It is concluded that becoming a drinker is an integral aspect of the process of adolscent development."}
{"id": "PMID:238078", "title": "Social mobility and alcoholism a comparison of alcholics with their fathers and brothers.", "content": "Men alcoholics entered the work force at a low socioeconomic level and though their status gradually increased, it never reached their fathers' or their brothers' level. Downward mobility in relation to significant others seems to play a role in the etiology of alcoholism.", "contents": "Social mobility and alcoholism a comparison of alcholics with their fathers and brothers. Men alcoholics entered the work force at a low socioeconomic level and though their status gradually increased, it never reached their fathers' or their brothers' level. Downward mobility in relation to significant others seems to play a role in the etiology of alcoholism."}
{"id": "PMID:238079", "title": "Behavior theraphy in alcoholism. A critical review of broad-spectrum approaches.", "content": "A review of the literature in behavior therapy for alcoholism suggests that broad-spectrum approaches based on analysis of the specific stimuli which trigger excessive drinking in individual patients are more effective than conventional methods. It appears too that controlled drinking is a reasonable treatment goal for some alcoholics.", "contents": "Behavior theraphy in alcoholism. A critical review of broad-spectrum approaches. A review of the literature in behavior therapy for alcoholism suggests that broad-spectrum approaches based on analysis of the specific stimuli which trigger excessive drinking in individual patients are more effective than conventional methods. It appears too that controlled drinking is a reasonable treatment goal for some alcoholics."}
{"id": "PMID:238080", "title": "A review of psychologically oriented treatment of alcoholism. II. The relative effectiveness of different treatment approaches and the effectiveness of treatment versus no treatment.", "content": "A review of 384 studies of psychologically oriented alcoholism treatment showed that differences in treatment methods did not significantly affect long-term outcome. Mean abstinence rates did not differ between treated and untreated alcoholics, but more treated than nontreated alcoholics improved, suggesting that formal treatment at least increases an alcoholic's chances of reducing his drinking problem.", "contents": "A review of psychologically oriented treatment of alcoholism. II. The relative effectiveness of different treatment approaches and the effectiveness of treatment versus no treatment. A review of 384 studies of psychologically oriented alcoholism treatment showed that differences in treatment methods did not significantly affect long-term outcome. Mean abstinence rates did not differ between treated and untreated alcoholics, but more treated than nontreated alcoholics improved, suggesting that formal treatment at least increases an alcoholic's chances of reducing his drinking problem."}
{"id": "PMID:238082", "title": "Quantitative microfluorimetry of formaldehyde induced fluorescence of dopamine in the caudate nucleus.", "content": "Quantitative microfluorimetric studies were carried out on the formaldehyde induced fluorescence of dopamine in nerve terminals of the nuc. caudatus putamen using the technique of Falck and Hillarp. After tyrosine hydroxylase inhibition produced by alpha-methyl-p-tyrosine (H 44/68) a time-dependent disappearance of the dopamine fluorescence occurred in an exponential manner, T1/22.6 hr. Apomorphine treatment resulted in a considerable counteraction of the H 44/68 induced reduction of the fluorescence, whereas treatment with haloperidol potentiated it. Administration of gamma-hydroxybutyrolactone led to a marked increase of the dopamine fluorescene. The present microfluorimetric results were in perfect agreement with chemical-analytical determinations of dopamine carried out under identical experimental conditions, and with those reported previously. The fluorescence intensities obtained in the nuc. caudatus putamen were found to be in the linear part of the dopamine fluorescence concentration relationship as observed in protein models. It may be concluded that by using microfluorimetric quantitation of the formaldehyde induced fluorescence in the nuc. caudatus putamen it is possible to obtain a reliable quantitation of the relative amount of dopamine in the dopamine nerve terminals.", "contents": "Quantitative microfluorimetry of formaldehyde induced fluorescence of dopamine in the caudate nucleus. Quantitative microfluorimetric studies were carried out on the formaldehyde induced fluorescence of dopamine in nerve terminals of the nuc. caudatus putamen using the technique of Falck and Hillarp. After tyrosine hydroxylase inhibition produced by alpha-methyl-p-tyrosine (H 44/68) a time-dependent disappearance of the dopamine fluorescence occurred in an exponential manner, T1/22.6 hr. Apomorphine treatment resulted in a considerable counteraction of the H 44/68 induced reduction of the fluorescence, whereas treatment with haloperidol potentiated it. Administration of gamma-hydroxybutyrolactone led to a marked increase of the dopamine fluorescene. The present microfluorimetric results were in perfect agreement with chemical-analytical determinations of dopamine carried out under identical experimental conditions, and with those reported previously. The fluorescence intensities obtained in the nuc. caudatus putamen were found to be in the linear part of the dopamine fluorescence concentration relationship as observed in protein models. It may be concluded that by using microfluorimetric quantitation of the formaldehyde induced fluorescence in the nuc. caudatus putamen it is possible to obtain a reliable quantitation of the relative amount of dopamine in the dopamine nerve terminals."}
{"id": "PMID:238083", "title": "Abnormal breathing patterns.", "content": "In health, breathing is regular and the respiratory rate is sufficiency constant to be useful as a vital sign of health and disease. This regularity depends on a complex interplay of chemical and neural control systems that operate automatically to reset the rate and depth of breathing as changes occur in posture and activity, to adjust the level of ventilation so that changes in gas tensions and pH in the blood and in the brain intersitial fluid are exceedingly modest despite wide swings in metabolic rate and in environmental conditions, and to coordinate ventilation and circulation so that the requirements of individual tissues for O2 delivery and CO2 removal are satisfied. Two broad categories of disorders can result from malfunction of these systems (Table 1): (1) disproportionate ventilation (too high or too low) for the level of metabolic activity, thereby producing severe abnormalities in blood gas tensions or in acid-base balance, and (2) an irregular breathing pattern without eliciting gross changes in blood gas tensions or in acid-base balance. Because of the complexity of the control system, each of these categories represents a final common pathway that can be produced in different ways. In this presentation, we will attempt to describe the general features that characterize the operation of the control system and some new technics that make it possible to trouble-shoot the malfunctioning system in order to identify the mechanism(s) responsible for the abnormality in breathing pattern.", "contents": "Abnormal breathing patterns. In health, breathing is regular and the respiratory rate is sufficiency constant to be useful as a vital sign of health and disease. This regularity depends on a complex interplay of chemical and neural control systems that operate automatically to reset the rate and depth of breathing as changes occur in posture and activity, to adjust the level of ventilation so that changes in gas tensions and pH in the blood and in the brain intersitial fluid are exceedingly modest despite wide swings in metabolic rate and in environmental conditions, and to coordinate ventilation and circulation so that the requirements of individual tissues for O2 delivery and CO2 removal are satisfied. Two broad categories of disorders can result from malfunction of these systems (Table 1): (1) disproportionate ventilation (too high or too low) for the level of metabolic activity, thereby producing severe abnormalities in blood gas tensions or in acid-base balance, and (2) an irregular breathing pattern without eliciting gross changes in blood gas tensions or in acid-base balance. Because of the complexity of the control system, each of these categories represents a final common pathway that can be produced in different ways. In this presentation, we will attempt to describe the general features that characterize the operation of the control system and some new technics that make it possible to trouble-shoot the malfunctioning system in order to identify the mechanism(s) responsible for the abnormality in breathing pattern."}
{"id": "PMID:238093", "title": "Mechanism for the paradoxical aciduria following alkali administration to prolonged-fasted patients.", "content": "Rapidly induced systemic alkalinization due to either sodium-lactate or sodium-bicarbonate infusion in prolonged-fasted subjects with steady-state ketoacidosis was associated with a decrease in urine pH. This decrease in urine pH from 5.50 to 5.20 was the result of a significant decrease in urinary ammonium excretion from 8.40 to 6.35 mEg/hr and was not accompanied by an increase in net acid excretion (11.3 vs. 10.6 mEg/hr). The decreased ammonium excretion is attributed to the raised pH of the proximal tubular fluid resulting in a less favorable pH gradient for gaseous ammonia entry. This would decrease gaseous ammonia generated in the loop of Henle for collecting duct buffering of secreted hydrogen ions.", "contents": "Mechanism for the paradoxical aciduria following alkali administration to prolonged-fasted patients. Rapidly induced systemic alkalinization due to either sodium-lactate or sodium-bicarbonate infusion in prolonged-fasted subjects with steady-state ketoacidosis was associated with a decrease in urine pH. This decrease in urine pH from 5.50 to 5.20 was the result of a significant decrease in urinary ammonium excretion from 8.40 to 6.35 mEg/hr and was not accompanied by an increase in net acid excretion (11.3 vs. 10.6 mEg/hr). The decreased ammonium excretion is attributed to the raised pH of the proximal tubular fluid resulting in a less favorable pH gradient for gaseous ammonia entry. This would decrease gaseous ammonia generated in the loop of Henle for collecting duct buffering of secreted hydrogen ions."}
{"id": "PMID:238094", "title": "The metabolic consequences of adrenergic blockade: a reveiw.", "content": "The effects in man of adrenergic blocking agents on plasma insulin, glucagon, growth hormone, and lipid metabolism are reviewed. Whereas basal insulin may be slightly inhibited by beta- and enhanced by alpha-adrenergic blockade, more marked suppression may be achieved under circumstances of high exogenous or endogenous catecholamine stimulation. The relative effects of beta1 or combined beta 1 and beta2 blockers in man are unknown. Glucagon release is probably provoked by beta- and inhibited by alpha-stimulation in man. Muscle glycogenolysis is inhibited by propranolol, and under situations of hepatic glycogen depletion, clinical hypopglycemia may occur. This may also account for the failure of significant hyperglycemia to be observed in short-term experiments on fasting subjects in whom insulin release may be suppressed and glucagon release enhanced. Growth-hormone release is enhanced by beta-adrenergic blockade. Free fatty acid formation in vivo is inhibited by intravenous beta blockade, but the effects of oral administration on triglyceride production and lipoprotein profiles remain uncertain. The inter-relationships between the effects of adrenergic blockade at different sites of hormone and substrate release are unclear but may have important consequences in alteration in carbohydrate tolerance and lipid metabolism. The relative effects of beta-blocking drugs with differing specificity must be determined.", "contents": "The metabolic consequences of adrenergic blockade: a reveiw. The effects in man of adrenergic blocking agents on plasma insulin, glucagon, growth hormone, and lipid metabolism are reviewed. Whereas basal insulin may be slightly inhibited by beta- and enhanced by alpha-adrenergic blockade, more marked suppression may be achieved under circumstances of high exogenous or endogenous catecholamine stimulation. The relative effects of beta1 or combined beta 1 and beta2 blockers in man are unknown. Glucagon release is probably provoked by beta- and inhibited by alpha-stimulation in man. Muscle glycogenolysis is inhibited by propranolol, and under situations of hepatic glycogen depletion, clinical hypopglycemia may occur. This may also account for the failure of significant hyperglycemia to be observed in short-term experiments on fasting subjects in whom insulin release may be suppressed and glucagon release enhanced. Growth-hormone release is enhanced by beta-adrenergic blockade. Free fatty acid formation in vivo is inhibited by intravenous beta blockade, but the effects of oral administration on triglyceride production and lipoprotein profiles remain uncertain. The inter-relationships between the effects of adrenergic blockade at different sites of hormone and substrate release are unclear but may have important consequences in alteration in carbohydrate tolerance and lipid metabolism. The relative effects of beta-blocking drugs with differing specificity must be determined."}
{"id": "PMID:238129", "title": "[Examination of the acute effect of prednisolone on the acid secretion of the stimulated gastric mucosa in man].", "content": "In comparison with the maximal acid stimulation produced by intravenous infusion of histalog (2 mg/kg bw/h), a single intravenous injection of 25 mg prednisolone during maximal acid stimulation produced by pentagastrin (1.5 mug/kg bw/h) does not cause a significant change of secretion rate or ionic composition of gastric juice in man. This suggests that there is a greater dependence of histalog stimulation than of pentagastrin stimulation on the normal secretion of glucocorticoids.", "contents": "[Examination of the acute effect of prednisolone on the acid secretion of the stimulated gastric mucosa in man]. In comparison with the maximal acid stimulation produced by intravenous infusion of histalog (2 mg/kg bw/h), a single intravenous injection of 25 mg prednisolone during maximal acid stimulation produced by pentagastrin (1.5 mug/kg bw/h) does not cause a significant change of secretion rate or ionic composition of gastric juice in man. This suggests that there is a greater dependence of histalog stimulation than of pentagastrin stimulation on the normal secretion of glucocorticoids."}
{"id": "PMID:238130", "title": "Culture medium alkalinization by dermatophyes. (Influence of time and temperature of incubation).", "content": "95 dermatophyte strains (12 of Trichophyton mentagrophytes, 12 of T. tonsurans, 11 of T. rubrum, 12 of T. megninii, 12 of T. violaceum, 2 of T. schoenleinii, 1 of T. soudanense, 12 of M. canis, 8 of Microsporum gypseum, 1 of M. ferrugineum and 12 of Epidermphoyton floccosum). 1 of Aspergillus niger, 1 of A. ochraceus, 1 of Paecilomyces sp., 1 of Penicillium sp. and 1 of Candida albicans were grown in Sabouraud liquid medium for the study of pH variation over 6 weeks at room temperature and after 4 weeks at 37 degrees C. All the dermatophyte strains alkalinized the medium. The highest pH values after 2-3 weeks' development in room temperature were produced by T. mentagrophytes, M. gypseum and M. canis, and the lowest by T. rubrum and T. violaceum. After the 4th week the alkalinizing activity became more marked for T. mentagrophytes and remained stationary for T. violaceum, In the 5th week the values produced by T. tonsurans were higher than those for M. gypseum, and those for E. floccosum and T. megninii were higher than those of M. canis. A similar behaviour was observed for T. rubrum and T. megninii and for M. canis, M. gypseum and M. ferrugineum. There seems to be a relation between the alkalinizing capacity and the rapidity and amount of the growth. At 37 degrees C both alkalinization and range of variation of the pH values of the medium became more noticeable for the strains of each species.", "contents": "Culture medium alkalinization by dermatophyes. (Influence of time and temperature of incubation). 95 dermatophyte strains (12 of Trichophyton mentagrophytes, 12 of T. tonsurans, 11 of T. rubrum, 12 of T. megninii, 12 of T. violaceum, 2 of T. schoenleinii, 1 of T. soudanense, 12 of M. canis, 8 of Microsporum gypseum, 1 of M. ferrugineum and 12 of Epidermphoyton floccosum). 1 of Aspergillus niger, 1 of A. ochraceus, 1 of Paecilomyces sp., 1 of Penicillium sp. and 1 of Candida albicans were grown in Sabouraud liquid medium for the study of pH variation over 6 weeks at room temperature and after 4 weeks at 37 degrees C. All the dermatophyte strains alkalinized the medium. The highest pH values after 2-3 weeks' development in room temperature were produced by T. mentagrophytes, M. gypseum and M. canis, and the lowest by T. rubrum and T. violaceum. After the 4th week the alkalinizing activity became more marked for T. mentagrophytes and remained stationary for T. violaceum, In the 5th week the values produced by T. tonsurans were higher than those for M. gypseum, and those for E. floccosum and T. megninii were higher than those of M. canis. A similar behaviour was observed for T. rubrum and T. megninii and for M. canis, M. gypseum and M. ferrugineum. There seems to be a relation between the alkalinizing capacity and the rapidity and amount of the growth. At 37 degrees C both alkalinization and range of variation of the pH values of the medium became more noticeable for the strains of each species."}
{"id": "PMID:238134", "title": "Beta structures of alternating polypeptides and their possible prebiotic significance.", "content": "A survey of the commonest amino acids formed in prebiotic conditions suggests that the earliest form of genetic coding may have specified polypeptides with a strong tendency to form stable Beta-sheet structure. Poly(Val-Lys), like other polypeptides in which hydrophobic and hydrophilic residues alternate, tends to form Beta structures. We show that bilayers with a hydrophobic interior and a hydrophilic exterior may be present in aqueous solution.", "contents": "Beta structures of alternating polypeptides and their possible prebiotic significance. A survey of the commonest amino acids formed in prebiotic conditions suggests that the earliest form of genetic coding may have specified polypeptides with a strong tendency to form stable Beta-sheet structure. Poly(Val-Lys), like other polypeptides in which hydrophobic and hydrophilic residues alternate, tends to form Beta structures. We show that bilayers with a hydrophobic interior and a hydrophilic exterior may be present in aqueous solution."}
{"id": "PMID:238137", "title": "Effects of depletion of brain catecholamines during the development of morphine dependence on precipitated withdrawal in rats.", "content": "The significance of long term depletion of brain catecholamines (CSs) for the development of morphine dependence and for the expression of morphine withdrawal was studied in rats which were implanted with morphine pellets for 10 days. CAs were depleted by inhibition of tyrosine-hydroxylase with alpha-methyl-tyrosine (AMT) or by destruction of catecholaminergic nerve terminals wit6-hydroxydopamine (6-OHDA). In the \"acute\" experiments these drugs were  applied within 24 hrs before precipitation of withdrawal; in the \"chronic\" experiments drug administration was started before the first implantation and in the case of AMT, continued repeatedly thereafter. With either method, \"acute\" depletion of brain CAs resulted in reduced intensity of withdrawal. When CAs were kept low through the whole time of morphine exposure and also at the time of withdrawal, the intensity of withdrawal was normal in the case of 6-OHDA administration and only slightly decreased in the case of AMT. When AMT administration was discontinued 40 hrs before precipitation of withdrawal the withdrawal pattern occurred with unchanged intensity. Our experimental data are compatible with the assumption that long lasting depletion of brain CAs is compensated for by induction of neuronal supersensitivity for noradrenaline (NA) and dopamine (DA). While both CAs play an important role in the full expression of the withdrawal syndrome their possible involvement in mechanisms leading to dependence seems to be unlikely although final statements cannot be made by the presented experiments.", "contents": "Effects of depletion of brain catecholamines during the development of morphine dependence on precipitated withdrawal in rats. The significance of long term depletion of brain catecholamines (CSs) for the development of morphine dependence and for the expression of morphine withdrawal was studied in rats which were implanted with morphine pellets for 10 days. CAs were depleted by inhibition of tyrosine-hydroxylase with alpha-methyl-tyrosine (AMT) or by destruction of catecholaminergic nerve terminals wit6-hydroxydopamine (6-OHDA). In the \"acute\" experiments these drugs were  applied within 24 hrs before precipitation of withdrawal; in the \"chronic\" experiments drug administration was started before the first implantation and in the case of AMT, continued repeatedly thereafter. With either method, \"acute\" depletion of brain CAs resulted in reduced intensity of withdrawal. When CAs were kept low through the whole time of morphine exposure and also at the time of withdrawal, the intensity of withdrawal was normal in the case of 6-OHDA administration and only slightly decreased in the case of AMT. When AMT administration was discontinued 40 hrs before precipitation of withdrawal the withdrawal pattern occurred with unchanged intensity. Our experimental data are compatible with the assumption that long lasting depletion of brain CAs is compensated for by induction of neuronal supersensitivity for noradrenaline (NA) and dopamine (DA). While both CAs play an important role in the full expression of the withdrawal syndrome their possible involvement in mechanisms leading to dependence seems to be unlikely although final statements cannot be made by the presented experiments."}
{"id": "PMID:238138", "title": "Localization in the CNA of adrenoceptors which facilitate a cardioinhibitory reflex.", "content": "In dogs (pentobarbitone, 25 mg/kg) the brain was removed rostrally to the pons, leaving the cerebellum intact (decerebrate animals). In other animals the cerebellum was additionally removed (bulbar animals). In all animals beta-adrenoceptors were blocked by toliprolol (5 mg/kg s.c.). Angiotensin (0.025-0.3mug/kg) was repeatedly injected i.v. and the resulting maximal reflex bradycardia was recorded. Intracisternal (i.ci.) injection of clonidine, 0.5 to 1 mug/kg, in decerebrate or i.v. injection of 10 or 30 mug/kg in bulbar animals significantly facilitated the reflex bradycardia. This effect was antagonised by a subsequent injection of piperoxan 50 mug/kg i.ci. in decerebrate or 1 mg/kg i.v. in bulbar animals. It is concluded that the facilitatory action of clonidine is mediated by alpha-adrenoceptors within the medulla oblongata.", "contents": "Localization in the CNA of adrenoceptors which facilitate a cardioinhibitory reflex. In dogs (pentobarbitone, 25 mg/kg) the brain was removed rostrally to the pons, leaving the cerebellum intact (decerebrate animals). In other animals the cerebellum was additionally removed (bulbar animals). In all animals beta-adrenoceptors were blocked by toliprolol (5 mg/kg s.c.). Angiotensin (0.025-0.3mug/kg) was repeatedly injected i.v. and the resulting maximal reflex bradycardia was recorded. Intracisternal (i.ci.) injection of clonidine, 0.5 to 1 mug/kg, in decerebrate or i.v. injection of 10 or 30 mug/kg in bulbar animals significantly facilitated the reflex bradycardia. This effect was antagonised by a subsequent injection of piperoxan 50 mug/kg i.ci. in decerebrate or 1 mg/kg i.v. in bulbar animals. It is concluded that the facilitatory action of clonidine is mediated by alpha-adrenoceptors within the medulla oblongata."}
{"id": "PMID:238139", "title": "Dopamine-induced neurogenic vasodilatation in isolated perfused muscle preparation of the dog.", "content": "Dopamine, injected into the lumbar aorta of the dog in doses which produce a reversible inhibition of synaptic transmission in the lumbar paravertebral ganglia (0.5-64x10-8 moles), produces a neurogenic vasodilatation in the isolated perfused hindleg or gracilis muscle. This was abolished by acute preganglionic decentralization and by administration into the perfused preparation of alpha-adrenoceptor blocking agents, but not of atropine or diphenhydramine. After decentralization, preganglionic electrical stimulation restored the dopamine-induced indirect vasodilatation. The neurogenic vasodilatation was also seen with intra-aortic injections of epinine (2-32x10-8 moles) and apomorphine (1.2-19.2x10-8 moles) and was preferentially blocked by haloperidol (0.26x10-6 moles). (-)-Noradrenaline, injected into the lumbar aorta in baroreceptor-denervated dogs, was found to be equipotent with dopamine in eliciting the neurogenic vasodilatation; this (-)-noradrenaline-induced effect was preferentially blocked by phentolamine (8x10-6 moles). The possibility that the neurogenic vasodilatation, which occurs upon intra-aortic injection of dopamine in the dog, is due to its gnaglionic-inhibitory effect is discussed.", "contents": "Dopamine-induced neurogenic vasodilatation in isolated perfused muscle preparation of the dog. Dopamine, injected into the lumbar aorta of the dog in doses which produce a reversible inhibition of synaptic transmission in the lumbar paravertebral ganglia (0.5-64x10-8 moles), produces a neurogenic vasodilatation in the isolated perfused hindleg or gracilis muscle. This was abolished by acute preganglionic decentralization and by administration into the perfused preparation of alpha-adrenoceptor blocking agents, but not of atropine or diphenhydramine. After decentralization, preganglionic electrical stimulation restored the dopamine-induced indirect vasodilatation. The neurogenic vasodilatation was also seen with intra-aortic injections of epinine (2-32x10-8 moles) and apomorphine (1.2-19.2x10-8 moles) and was preferentially blocked by haloperidol (0.26x10-6 moles). (-)-Noradrenaline, injected into the lumbar aorta in baroreceptor-denervated dogs, was found to be equipotent with dopamine in eliciting the neurogenic vasodilatation; this (-)-noradrenaline-induced effect was preferentially blocked by phentolamine (8x10-6 moles). The possibility that the neurogenic vasodilatation, which occurs upon intra-aortic injection of dopamine in the dog, is due to its gnaglionic-inhibitory effect is discussed."}
{"id": "PMID:238140", "title": "The influence of imipramine on dopamine-induced ganglionic inhibition and neurogenic vasodilatation in the dog.", "content": "Imipramine potentiates the dopamine-induced inhibition in the paravertebral lumbar ganglia of the dog. Potentiation by imipramine of the dopamine-induced neurogenic vasodilatation in the isolated perfused gracilis muscle, is seen in cross-circulation preparations only, where imipramine is injected into the perfusion circuit of an isolated perfused gracilis muscle, it antagonizes the dopamine-induced neurogenic vasodilatation. When imipramine is injected intravenously into a dog with an autoperfused gracilis muscle, the peripheral antagonism masks the potentiating effect at the ganglionic level, and the dopamine-induced neurogenic vasodilatation is abolished.", "contents": "The influence of imipramine on dopamine-induced ganglionic inhibition and neurogenic vasodilatation in the dog. Imipramine potentiates the dopamine-induced inhibition in the paravertebral lumbar ganglia of the dog. Potentiation by imipramine of the dopamine-induced neurogenic vasodilatation in the isolated perfused gracilis muscle, is seen in cross-circulation preparations only, where imipramine is injected into the perfusion circuit of an isolated perfused gracilis muscle, it antagonizes the dopamine-induced neurogenic vasodilatation. When imipramine is injected intravenously into a dog with an autoperfused gracilis muscle, the peripheral antagonism masks the potentiating effect at the ganglionic level, and the dopamine-induced neurogenic vasodilatation is abolished."}
{"id": "PMID:238141", "title": "Further evidence for a cAMP dependent regulation of tyrosine-3-monoxygenase induction in adrenal medulla: effect of denervation.", "content": "Unilateral adrenal denervation caused a gradual decrease of adenylate cyclase activity in rat adrenal medulla. The extent of the increase in adrenal medullary 3',5'-cyclic adenosine monophosphate (cAMP) content elicited by injections of carbamylcholine declined gradually folling adrenal denervation. Three or nine days after denervation carbamylcholine caused rise of cAMP and a delayed increase of tyrosine-3-mono-oxygenase (TH) activity of similar magnitude in intact and denervated adrenal medullae. However, after an interval of 15 days or longer following denervation the increase in TH activity elicited by carbamylcholine was greatly reduced. These results support previous proposals that cAMP is involved as a second messenger in the trans-synaptic induction of TH.", "contents": "Further evidence for a cAMP dependent regulation of tyrosine-3-monoxygenase induction in adrenal medulla: effect of denervation. Unilateral adrenal denervation caused a gradual decrease of adenylate cyclase activity in rat adrenal medulla. The extent of the increase in adrenal medullary 3',5'-cyclic adenosine monophosphate (cAMP) content elicited by injections of carbamylcholine declined gradually folling adrenal denervation. Three or nine days after denervation carbamylcholine caused rise of cAMP and a delayed increase of tyrosine-3-mono-oxygenase (TH) activity of similar magnitude in intact and denervated adrenal medullae. However, after an interval of 15 days or longer following denervation the increase in TH activity elicited by carbamylcholine was greatly reduced. These results support previous proposals that cAMP is involved as a second messenger in the trans-synaptic induction of TH."}
{"id": "PMID:238161", "title": "Properties of rat cerebral cortex neuronal nuclear surfaces: electrokinetic parameters.", "content": "Rat cerebral cortex neuronal nuclei were isolated by a mild technique utilizing sucrose; citric acid was not used in the isolation of the nuclei. These nuclei in 0.0145 M NaC1, 4.5 per cent sorbitol, and 0.6 mM NaHCO3 with pH 7.2 plus or minus 0.1 at 25 degrees C had an electrophoretic morbidity of minus 2.01 mum-s(-1)-V(-1)-cm(-1). The mobility curves for the brain nuclei indicated that the surface had an acid-dissociable group of pK APPROXIMATELY 2.7. Nuclei treated with 50 mg neurominidase/mg particle protein had a mobility of minus 1.4 mum-s(-1)-V(-1)-cm(-1). DNase or RNase at 50 mug/mg protein had no effect on the mobility of the isolated nuclei. Concanavalin A at 50 mug/mg protein decreased the nuclei electrophoretic mobility to minus 1.82 mum-s(-1)-V(-1)-cm(-1). The results are interpreted to mean that the brain nuclear external surface contains terminal sialic acid residues, but it is completely devoid of nucleic acids, and it binds canavalin A.", "contents": "Properties of rat cerebral cortex neuronal nuclear surfaces: electrokinetic parameters. Rat cerebral cortex neuronal nuclei were isolated by a mild technique utilizing sucrose; citric acid was not used in the isolation of the nuclei. These nuclei in 0.0145 M NaC1, 4.5 per cent sorbitol, and 0.6 mM NaHCO3 with pH 7.2 plus or minus 0.1 at 25 degrees C had an electrophoretic morbidity of minus 2.01 mum-s(-1)-V(-1)-cm(-1). The mobility curves for the brain nuclei indicated that the surface had an acid-dissociable group of pK APPROXIMATELY 2.7. Nuclei treated with 50 mg neurominidase/mg particle protein had a mobility of minus 1.4 mum-s(-1)-V(-1)-cm(-1). DNase or RNase at 50 mug/mg protein had no effect on the mobility of the isolated nuclei. Concanavalin A at 50 mug/mg protein decreased the nuclei electrophoretic mobility to minus 1.82 mum-s(-1)-V(-1)-cm(-1). The results are interpreted to mean that the brain nuclear external surface contains terminal sialic acid residues, but it is completely devoid of nucleic acids, and it binds canavalin A."}
{"id": "PMID:238162", "title": "Cerebellar N-acetyl-beta-D-glucosaminidase: a study of the enzyme in bulk-isolated purkinje and granule cells.", "content": "The specific activity of the lysosomal glycosidase N-acetyl-beta-D-glucosaminidase was determined in Purkinje cell bodies and granule cells isolated in bulb from cerebella of 13-, 15- and 18-day-old rats, and somewhat higher values were found for the enzyme in the Purkinje cell bodies. Although the pH profile of N-acetyl-beta-D-glucosaminidase in both neuronal types was similar, the activity in the granule cells exhibited two \"pH optima\". The glycosidase could be readily solubilized from both neuronal types by repeated freezing and thawing and, upon sedimentation in sucrose density gradients, the solubilized activity appeared as two distinct molecular components. The findings demonstrate the feasibility of detailed and direct comparative studies of neuron-specific patterns of enzymatic development and the excellent suitability of bulk-isolated cells for this purpose.", "contents": "Cerebellar N-acetyl-beta-D-glucosaminidase: a study of the enzyme in bulk-isolated purkinje and granule cells. The specific activity of the lysosomal glycosidase N-acetyl-beta-D-glucosaminidase was determined in Purkinje cell bodies and granule cells isolated in bulb from cerebella of 13-, 15- and 18-day-old rats, and somewhat higher values were found for the enzyme in the Purkinje cell bodies. Although the pH profile of N-acetyl-beta-D-glucosaminidase in both neuronal types was similar, the activity in the granule cells exhibited two \"pH optima\". The glycosidase could be readily solubilized from both neuronal types by repeated freezing and thawing and, upon sedimentation in sucrose density gradients, the solubilized activity appeared as two distinct molecular components. The findings demonstrate the feasibility of detailed and direct comparative studies of neuron-specific patterns of enzymatic development and the excellent suitability of bulk-isolated cells for this purpose."}
{"id": "PMID:238163", "title": "On the presence of a MSH-release inhibiting system in the rat neurointermediate lobe.", "content": "Rat neurointermediate lobes were superfused in vitro and showed a stable secretion rate of MSH after 30 min. MSH secretion from lobes of untreated rats was reversibly inhibited during superfusion with medium containing 45 mM K+. This inhibition could not be induced using lobes from median eminence lesioned or reserpinized rats. Superfusion with 45 mM K+ also induced release of dopamine from lobes preincubated with the labeled transmitter. It is concluded that the MSH-release inhibiting system present in the rat neurointermediate lobe may be identical to the dopaminergic arcuate-intermediate lobe system.", "contents": "On the presence of a MSH-release inhibiting system in the rat neurointermediate lobe. Rat neurointermediate lobes were superfused in vitro and showed a stable secretion rate of MSH after 30 min. MSH secretion from lobes of untreated rats was reversibly inhibited during superfusion with medium containing 45 mM K+. This inhibition could not be induced using lobes from median eminence lesioned or reserpinized rats. Superfusion with 45 mM K+ also induced release of dopamine from lobes preincubated with the labeled transmitter. It is concluded that the MSH-release inhibiting system present in the rat neurointermediate lobe may be identical to the dopaminergic arcuate-intermediate lobe system."}
{"id": "PMID:238164", "title": "Effects of melatonin on neurotransmitter uptake and release by synaptosome-rich homogenates of the rat hypothalamus.", "content": "Preincubation of synaptosome-rich homogenates of rat hypothalamus with melatonin resulted in significant decreases of norepinephrine, serotonin, dopamine and glutamate uptake. Melatonin inhibition was noncompetitive; apparent Km's of initial uptake processes were: (2.5 +/- 0.3) x 10(-7) M for norepinephrine, (2.6 +/- 0.3) x 10(-7) M for serotonin, (2.4 +/- 0.4) x 10(-7) M for dopamine and (1.0 +/- 0.3) x 10(-7) M for glutamate. Apparent Ki's for melatonin inhibition of transmitter uptake were: 0.64 +/- 0.14 mM (norepinephrine), 0.23 +/- mM (serotonin), 0.51 +/- 0.08 mM (dopamine) and 1.21 +/- 0.10 mM (glutamate). Transmitter release evoked by increasing [K+] in medium to 30 mM was augmented by melatonin in a dose-dependent manner. Maximal effects were observed on serotonin release. Accumulation of 3H-melatonin within synaptosome-rich homogenates did not exhibit differences between 0 and 37 degrees C, indicating that the uptake of the hormone was not an active process. These results suggest that exogenously-administered melatonin may affect neurotransmitter accumulation and release in the hypothalamus by modification of the transmitter uptake mechanism rather than by competition with the transmitter for its uptake pump.", "contents": "Effects of melatonin on neurotransmitter uptake and release by synaptosome-rich homogenates of the rat hypothalamus. Preincubation of synaptosome-rich homogenates of rat hypothalamus with melatonin resulted in significant decreases of norepinephrine, serotonin, dopamine and glutamate uptake. Melatonin inhibition was noncompetitive; apparent Km's of initial uptake processes were: (2.5 +/- 0.3) x 10(-7) M for norepinephrine, (2.6 +/- 0.3) x 10(-7) M for serotonin, (2.4 +/- 0.4) x 10(-7) M for dopamine and (1.0 +/- 0.3) x 10(-7) M for glutamate. Apparent Ki's for melatonin inhibition of transmitter uptake were: 0.64 +/- 0.14 mM (norepinephrine), 0.23 +/- mM (serotonin), 0.51 +/- 0.08 mM (dopamine) and 1.21 +/- 0.10 mM (glutamate). Transmitter release evoked by increasing [K+] in medium to 30 mM was augmented by melatonin in a dose-dependent manner. Maximal effects were observed on serotonin release. Accumulation of 3H-melatonin within synaptosome-rich homogenates did not exhibit differences between 0 and 37 degrees C, indicating that the uptake of the hormone was not an active process. These results suggest that exogenously-administered melatonin may affect neurotransmitter accumulation and release in the hypothalamus by modification of the transmitter uptake mechanism rather than by competition with the transmitter for its uptake pump."}
{"id": "PMID:238176", "title": "Studies on tissue factor activity and production by leukocytes of human umbilical cord and adult origin.", "content": "Human adult and umbilical cord-derived leukocytes were shown to be capable of generating tissue factor activity on exposure to endotoxin and to reduced pH. Blood for leukocyte separation was collected from normal adults and from newly delivered sections of umbilical cord and mixed leukocyte preparations were obtained by separation over methyl cellulose Hypaque. The coagulant activity of the cell suspension was assayed using a one-stage or two-stage method. Cord-derived leukocytes were shown to develop greater coagulant activity than adult-derived leukocytes when stimulated by endotoxin in vitro at 2,000 cells/mm-3. This response to endotoxin was partially inhibited by prior exposure of the cells to prostaglandin (PG) E1 an to L-epinephrine. Acetylcholine stimulated the production of coagulant activity in the absence of endotoxin. Both cord and adult-derived leukocytes (20,000/mm-3) developed coagulant activity when exposed to pH reduction by lactic or hydrochloric acids and this activity was shown to be tissue factor.", "contents": "Studies on tissue factor activity and production by leukocytes of human umbilical cord and adult origin. Human adult and umbilical cord-derived leukocytes were shown to be capable of generating tissue factor activity on exposure to endotoxin and to reduced pH. Blood for leukocyte separation was collected from normal adults and from newly delivered sections of umbilical cord and mixed leukocyte preparations were obtained by separation over methyl cellulose Hypaque. The coagulant activity of the cell suspension was assayed using a one-stage or two-stage method. Cord-derived leukocytes were shown to develop greater coagulant activity than adult-derived leukocytes when stimulated by endotoxin in vitro at 2,000 cells/mm-3. This response to endotoxin was partially inhibited by prior exposure of the cells to prostaglandin (PG) E1 an to L-epinephrine. Acetylcholine stimulated the production of coagulant activity in the absence of endotoxin. Both cord and adult-derived leukocytes (20,000/mm-3) developed coagulant activity when exposed to pH reduction by lactic or hydrochloric acids and this activity was shown to be tissue factor."}
{"id": "PMID:238177", "title": "The enzymes of lecithin biosynthesis in human neonatal lungs. IV. Phosphorylcholine cytidyltransferase.", "content": "Phosphorylcholine cytidyltransferase, the enzyme which catalyzes the transfer of phosphorylcholine to cytidine 5'-triphosphate to form CDP-choline, was studied for the first time in human neonatal lung. The assay of product synthesis was linear for 10-20 min and up to 12 mg protein. The pH optimum was 6-6.5. The Km of CTP was 2.0 times 10- minus 3 M, and the Km of phosphorylcholine was 0.25 times 10- minus 3 M. The true Vmax was 10 nmol CDP-choline/mg protein/10 min. The enzyme was stable under frozen conditions. Oxygen had no apparent affect on enzyme activity.", "contents": "The enzymes of lecithin biosynthesis in human neonatal lungs. IV. Phosphorylcholine cytidyltransferase. Phosphorylcholine cytidyltransferase, the enzyme which catalyzes the transfer of phosphorylcholine to cytidine 5'-triphosphate to form CDP-choline, was studied for the first time in human neonatal lung. The assay of product synthesis was linear for 10-20 min and up to 12 mg protein. The pH optimum was 6-6.5. The Km of CTP was 2.0 times 10- minus 3 M, and the Km of phosphorylcholine was 0.25 times 10- minus 3 M. The true Vmax was 10 nmol CDP-choline/mg protein/10 min. The enzyme was stable under frozen conditions. Oxygen had no apparent affect on enzyme activity."}
{"id": "PMID:238178", "title": "Smallpox vaccination reactions, prophylaxis, and therapy of complications.", "content": "Smallpox vaccination in the United States is a routine public health measure which has been under intensive review during the last decade. The most frequently occurring adverse reactions to vaccination are benign and require little or no systemic therapy. These reactions include accidental infection, erythematous and urticarial rash, and generalized vaccinia. Chickenpox occurring concurrently with vaccination presents no problem unless vaccinia has widely superinfected the chickenpox lesions. There is no risk to the pregnant woman who is vaccinated, but there is a slight risk that the fetus will develop fetal vaccinia. The vaccinia does not cause congenital malformations. Vaccinia hyperimmune globulin (VIG) in prophylactic dosage may be given to a pregnant woman who is traveling to a smallpox infected or endemic area in order to prevent fetal vaccinia. Vaccinia necrosum and eczema vaccinatum require vigorous systemic therapy with VIG, and often thiosemicarbazone. Post-vaccinial encephalitis, while frequently serious, has not been shown to be ameliorated by VIG therapy, although there are data which suggest VIG has some value in prophylaxis for encephalitis. Prophylaxis, prompt recognition, and proper therapy may reduce the fatality rates of these complications. Revaccination of patients who have suffered a complication is a frequent clinical problem. Revaccination of an individual who has had post-vaccinial encephalitis or vaccinia necrosum is contraindicated unless the risk of contracting smallpox outweighs the risk of the above two diseases. Revaccination of children who have had eczema vaccinatum is not contraindicated. Revaccination of children with a history of accidental infection or erythematous or urticarial rash presents no known or theoretically increased risk.", "contents": "Smallpox vaccination reactions, prophylaxis, and therapy of complications. Smallpox vaccination in the United States is a routine public health measure which has been under intensive review during the last decade. The most frequently occurring adverse reactions to vaccination are benign and require little or no systemic therapy. These reactions include accidental infection, erythematous and urticarial rash, and generalized vaccinia. Chickenpox occurring concurrently with vaccination presents no problem unless vaccinia has widely superinfected the chickenpox lesions. There is no risk to the pregnant woman who is vaccinated, but there is a slight risk that the fetus will develop fetal vaccinia. The vaccinia does not cause congenital malformations. Vaccinia hyperimmune globulin (VIG) in prophylactic dosage may be given to a pregnant woman who is traveling to a smallpox infected or endemic area in order to prevent fetal vaccinia. Vaccinia necrosum and eczema vaccinatum require vigorous systemic therapy with VIG, and often thiosemicarbazone. Post-vaccinial encephalitis, while frequently serious, has not been shown to be ameliorated by VIG therapy, although there are data which suggest VIG has some value in prophylaxis for encephalitis. Prophylaxis, prompt recognition, and proper therapy may reduce the fatality rates of these complications. Revaccination of patients who have suffered a complication is a frequent clinical problem. Revaccination of an individual who has had post-vaccinial encephalitis or vaccinia necrosum is contraindicated unless the risk of contracting smallpox outweighs the risk of the above two diseases. Revaccination of children who have had eczema vaccinatum is not contraindicated. Revaccination of children with a history of accidental infection or erythematous or urticarial rash presents no known or theoretically increased risk."}
{"id": "PMID:238179", "title": "Acceptable and controversial approaches to treating the child with learning disabilities.", "content": "There are many professionals in multiple disciplines developing approaches for helping children with learning disabilities. Much of these data and reports are published in journals normally not read by physicians. On occasion, such publications are reported in newspapers or lay magazines. Thus, parents may know of ideas and suggestions before the professional. It is understandable that the parent of a handicapped child would continually seek out improved ways of helping his or her child. The treatment of choice is basically special education. Medication will minimize the hyperactivity and distractability; psychotherapy may minimize the emotional effects. However, special educational therapy for the underlying learning disabilities is essential. No one yet has a rapid or \"guaranteed\" cure. Parents are often caught in the middle. They turn to their physician for guidance. It is the purpose of this paper to review the significant literature in an effort to assist the family physician in providing this guidance.", "contents": "Acceptable and controversial approaches to treating the child with learning disabilities. There are many professionals in multiple disciplines developing approaches for helping children with learning disabilities. Much of these data and reports are published in journals normally not read by physicians. On occasion, such publications are reported in newspapers or lay magazines. Thus, parents may know of ideas and suggestions before the professional. It is understandable that the parent of a handicapped child would continually seek out improved ways of helping his or her child. The treatment of choice is basically special education. Medication will minimize the hyperactivity and distractability; psychotherapy may minimize the emotional effects. However, special educational therapy for the underlying learning disabilities is essential. No one yet has a rapid or \"guaranteed\" cure. Parents are often caught in the middle. They turn to their physician for guidance. It is the purpose of this paper to review the significant literature in an effort to assist the family physician in providing this guidance."}
{"id": "PMID:238183", "title": "Necleoside conformations. 19. Temperature and pH effects on the conformation of guanosine phosphates.", "content": "Proton magnetic resonance spectra at 250 MHz were measured as a function of temperature and pH of the three guanosine phosphates. From these data and previously published work the conformational parameters of these compounds were determinated. The phosphate group of Guo-5'-P changes its conformation around the C-O bond and its rotation is relatively slow at 20 degrees. At neutral pD the S conformation is favoured and the N form at acid pD. This conformational change is paralleled by a change in exocyclic rotamer distribution and takes place at the pK of the protonation of the base on N-7. Although correlation appears to exist between the various conformations, notable exceptions exist.", "contents": "Necleoside conformations. 19. Temperature and pH effects on the conformation of guanosine phosphates. Proton magnetic resonance spectra at 250 MHz were measured as a function of temperature and pH of the three guanosine phosphates. From these data and previously published work the conformational parameters of these compounds were determinated. The phosphate group of Guo-5'-P changes its conformation around the C-O bond and its rotation is relatively slow at 20 degrees. At neutral pD the S conformation is favoured and the N form at acid pD. This conformational change is paralleled by a change in exocyclic rotamer distribution and takes place at the pK of the protonation of the base on N-7. Although correlation appears to exist between the various conformations, notable exceptions exist."}
{"id": "PMID:238184", "title": "Cyclization of uridine monophosphate by diethyl pyrocarbonate.", "content": "Reaction between diethyl pyrocarbonate and uridine 2'-phosphate or uridine 3'-phosphate leads to the formation in high yields of uridine 2':3'-cyclic phosphate. This reaction product was identified in experiments involving (a) ultraviolet spectrophotometry, (b) paper chromatography, (c) high voltage paper electrophoresis at both  pH 3.5 and 7.4, (d) acid hydrolysis, and (e) digestion with pancreatic ribonuclease.", "contents": "Cyclization of uridine monophosphate by diethyl pyrocarbonate. Reaction between diethyl pyrocarbonate and uridine 2'-phosphate or uridine 3'-phosphate leads to the formation in high yields of uridine 2':3'-cyclic phosphate. This reaction product was identified in experiments involving (a) ultraviolet spectrophotometry, (b) paper chromatography, (c) high voltage paper electrophoresis at both  pH 3.5 and 7.4, (d) acid hydrolysis, and (e) digestion with pancreatic ribonuclease."}
{"id": "PMID:238188", "title": "The dual action of meclofenamate on the contractile response to PGF2 alpha in the guinea-pig trachea.", "content": "Indomethacin and meclofenamate (1 mug/ml) enhance contractile action of PGF2 alpha (5-20 mug) in guinea-pig tracheas superfused with Tyrode solution (5 ml/min). Unlike indomethacin, meclofenamate at a concentration of 10 mug/ml antagonizes contractions of guinea-pig tracheas produced by PGF2 alpha (5-20 mug), while the contractile action of histamine (0-5-2-0 mug) is enhanced. It is concluded that low concentrations of meclofenamate (1 mug/ml) inhibit prostaglandin biosynthesis in tracheal smooth muscles and therefore contractile action of exogenous PGF2 alpha is enhanced, while meclofenamate at a high concentration (10 mug/ml) blocks the receptor sites for PGF2 alpha.", "contents": "The dual action of meclofenamate on the contractile response to PGF2 alpha in the guinea-pig trachea. Indomethacin and meclofenamate (1 mug/ml) enhance contractile action of PGF2 alpha (5-20 mug) in guinea-pig tracheas superfused with Tyrode solution (5 ml/min). Unlike indomethacin, meclofenamate at a concentration of 10 mug/ml antagonizes contractions of guinea-pig tracheas produced by PGF2 alpha (5-20 mug), while the contractile action of histamine (0-5-2-0 mug) is enhanced. It is concluded that low concentrations of meclofenamate (1 mug/ml) inhibit prostaglandin biosynthesis in tracheal smooth muscles and therefore contractile action of exogenous PGF2 alpha is enhanced, while meclofenamate at a high concentration (10 mug/ml) blocks the receptor sites for PGF2 alpha."}
{"id": "PMID:238193", "title": "[Participation of thyroxine in the regulation of the rate of isocitrate dehydrogenase reactions in the brain and liver].", "content": "A study was made of the effect of thyroxin on the activity of NAD- and NADP-dependent isocitratedehydrogenases in the brain and the liver of chick embryos. It was found that in both of the organs thyroxin accelerated isocitrate oxidation in the mitochondria through the NAD-dependent route and elevated the velocity of the NADP-isocitratedehydrogenase reaction in the citoplasm. At the same time the activity of the mitochondrial NADP-dependent isocitratedehydrogenase increased after the administration of the hormone to the embryos only in the mitochondria of the brain cells; this was apparently associated with the intensive biosynthesis of specific lipids in the developing brain. There was noted a more marked change in the activity of the enzymes in the 18-day embryos, in comparison with the 12-day ones.", "contents": "[Participation of thyroxine in the regulation of the rate of isocitrate dehydrogenase reactions in the brain and liver]. A study was made of the effect of thyroxin on the activity of NAD- and NADP-dependent isocitratedehydrogenases in the brain and the liver of chick embryos. It was found that in both of the organs thyroxin accelerated isocitrate oxidation in the mitochondria through the NAD-dependent route and elevated the velocity of the NADP-isocitratedehydrogenase reaction in the citoplasm. At the same time the activity of the mitochondrial NADP-dependent isocitratedehydrogenase increased after the administration of the hormone to the embryos only in the mitochondria of the brain cells; this was apparently associated with the intensive biosynthesis of specific lipids in the developing brain. There was noted a more marked change in the activity of the enzymes in the 18-day embryos, in comparison with the 12-day ones."}
{"id": "PMID:238213", "title": "Enzymatic S-de-ethylation and the mechanism of S-dealkylation.", "content": "An NADPH- and oxygen-dependent enzymatic system responsible for the formation of acetaldehyde from ethylthioethers is present in the 9000 g supernatant fraction of rat liver. This system appears to be quite similar to the one responsible for the formation of formaldehyde from methylthioethers. Although both of these systems appears to be microsomal mixedoxidase systems, several anomalous findings regarding the mechanism of microsomal S-dealkylation have been observed and have led us to the conclusion that the mechanism of this reaction is more complex than originally believed. A scheme is postulated by which an enzyme in the soluble fraction causes microsomal sulfoxidation of alkylthioethers to alkylsulfoxides, followed by metabolism of the alkylsulfoxides to aldehydes.", "contents": "Enzymatic S-de-ethylation and the mechanism of S-dealkylation. An NADPH- and oxygen-dependent enzymatic system responsible for the formation of acetaldehyde from ethylthioethers is present in the 9000 g supernatant fraction of rat liver. This system appears to be quite similar to the one responsible for the formation of formaldehyde from methylthioethers. Although both of these systems appears to be microsomal mixedoxidase systems, several anomalous findings regarding the mechanism of microsomal S-dealkylation have been observed and have led us to the conclusion that the mechanism of this reaction is more complex than originally believed. A scheme is postulated by which an enzyme in the soluble fraction causes microsomal sulfoxidation of alkylthioethers to alkylsulfoxides, followed by metabolism of the alkylsulfoxides to aldehydes."}
{"id": "PMID:238214", "title": "The effect of cyanate on the clotting proteins and platelet function.", "content": "Cyanate reacts with unchanged amino groups of various proteins in a specific irreversible carbamylation reaction. The effect of this molecule on the clotting process and the effects of carbamylation on the clotting proteins and platelet functions were investigated in vitro. An immediate effect on the clotting proteins, not related to pH, was seen in the screening tests prothrombin time, partial thromboplastin time and thrombin time at the highest concentration (100 mM), to a lesser degree at the lower concentration (10 mM). These changes reflected decreases of 19 and 36% respectively in Factor V and X activity, an inhibition of 63-75% of Factors VII, IX, X and XI activity, and 80% inhibition of thrombin activity. The inhibitory changes of carbamylation increased with time. No changes were seen in the activity of Factors I and VIII. Platelet function studies revealed no inhibition of Factor III release; aggregation was abnormal only at high concentrations with epinephrine and collagen induction and partially reversible by resuspension in normal plasma.", "contents": "The effect of cyanate on the clotting proteins and platelet function. Cyanate reacts with unchanged amino groups of various proteins in a specific irreversible carbamylation reaction. The effect of this molecule on the clotting process and the effects of carbamylation on the clotting proteins and platelet functions were investigated in vitro. An immediate effect on the clotting proteins, not related to pH, was seen in the screening tests prothrombin time, partial thromboplastin time and thrombin time at the highest concentration (100 mM), to a lesser degree at the lower concentration (10 mM). These changes reflected decreases of 19 and 36% respectively in Factor V and X activity, an inhibition of 63-75% of Factors VII, IX, X and XI activity, and 80% inhibition of thrombin activity. The inhibitory changes of carbamylation increased with time. No changes were seen in the activity of Factors I and VIII. Platelet function studies revealed no inhibition of Factor III release; aggregation was abnormal only at high concentrations with epinephrine and collagen induction and partially reversible by resuspension in normal plasma."}
{"id": "PMID:238215", "title": "Effect of maternal protein deprivation on enzymatic development in newborn rats.", "content": "Postnatal development of liver tyrosine aminotransferase and glucose-6-phosphatase, expressed as activity per gram of liver, occurred as rapidly in pups from pregnant rats fed throughout gestation a diet containing only 4% of casein as in pups from those fed the control diet containing 18% of casein supplemented with 0.3% of L-methionine. Total enzyme activity per liver was lower in pups from protein-restricted dams due to their smaller liver size. Dams fed the 4% casein diet during pregnancy gained much less weight than those fed the control diet and produced pups that weighed significantly less than control pups. Reproductive performance of a few dams fed 6% casein diets with or without amino acid supplements during gestation was comparable to that of dams fed the control diet. Litter size was not significantly reduced by the low-protein intake.", "contents": "Effect of maternal protein deprivation on enzymatic development in newborn rats. Postnatal development of liver tyrosine aminotransferase and glucose-6-phosphatase, expressed as activity per gram of liver, occurred as rapidly in pups from pregnant rats fed throughout gestation a diet containing only 4% of casein as in pups from those fed the control diet containing 18% of casein supplemented with 0.3% of L-methionine. Total enzyme activity per liver was lower in pups from protein-restricted dams due to their smaller liver size. Dams fed the 4% casein diet during pregnancy gained much less weight than those fed the control diet and produced pups that weighed significantly less than control pups. Reproductive performance of a few dams fed 6% casein diets with or without amino acid supplements during gestation was comparable to that of dams fed the control diet. Litter size was not significantly reduced by the low-protein intake."}
{"id": "PMID:238216", "title": "Uptake of 67Cu by ceruloplasmin in vitro.", "content": "Solutions of human ceruloplasmin, in Tris buffer at pH values between 6 and 7.5, readily took up carrier-free 67Cu2+, but only when the substrate, rho-phenylenediamine, was added.", "contents": "Uptake of 67Cu by ceruloplasmin in vitro. Solutions of human ceruloplasmin, in Tris buffer at pH values between 6 and 7.5, readily took up carrier-free 67Cu2+, but only when the substrate, rho-phenylenediamine, was added."}
{"id": "PMID:238217", "title": "Unusual venoconstrictor effects of angiotensin II.", "content": "Cumulative dose-response curves to angiotensin II were performed on helical strips from canine lateral saphenous vein. Threshold concentrations were in the range of 10(-18)-10(-17)M. Increases in angiotensin from 10(-17)-10(-12)M failed to elicit further increases in tension. Subsequent increases in angiotensin concentration from 10(-11)-10(-7)M again produced dose-related increases in tension. Repeated dose-response curves in the same strips showed reduced maximal response. Responses to low concentrations of angiotensin were attenuated by low concentrations of phentolamine. These results suggest that, at extremely low concentrations angiotensin produced marked contractions in canine saphenous vein strips by releasing endogenous norepinephrine from sympathetic nerve terminals.", "contents": "Unusual venoconstrictor effects of angiotensin II. Cumulative dose-response curves to angiotensin II were performed on helical strips from canine lateral saphenous vein. Threshold concentrations were in the range of 10(-18)-10(-17)M. Increases in angiotensin from 10(-17)-10(-12)M failed to elicit further increases in tension. Subsequent increases in angiotensin concentration from 10(-11)-10(-7)M again produced dose-related increases in tension. Repeated dose-response curves in the same strips showed reduced maximal response. Responses to low concentrations of angiotensin were attenuated by low concentrations of phentolamine. These results suggest that, at extremely low concentrations angiotensin produced marked contractions in canine saphenous vein strips by releasing endogenous norepinephrine from sympathetic nerve terminals."}
{"id": "PMID:238218", "title": "Acid-secretory effects of pentagastrin, histamine, urecholine, DBcAMP, and cBMP in isolated stomachs of fed and fasted rats.", "content": "Pentagastrin, histamine, urecholine, DBcAMP, and cGMP were all potent stimulants of acid secretion in the isolated stomach of the fed rat. With the exception of histamine and cGMP, all of these compounds were inactive when the stomach of the fasted rat was used. Pentagastrin was most effective when given on the serosal surface while histamine was equally potent whether it was added to the mucosal or serosal surface of the isolated stomach. The test would appear to be a relatively simply, but effective system for studying the basic mechanisms of action of several important secretagogues in the rat.", "contents": "Acid-secretory effects of pentagastrin, histamine, urecholine, DBcAMP, and cBMP in isolated stomachs of fed and fasted rats. Pentagastrin, histamine, urecholine, DBcAMP, and cGMP were all potent stimulants of acid secretion in the isolated stomach of the fed rat. With the exception of histamine and cGMP, all of these compounds were inactive when the stomach of the fasted rat was used. Pentagastrin was most effective when given on the serosal surface while histamine was equally potent whether it was added to the mucosal or serosal surface of the isolated stomach. The test would appear to be a relatively simply, but effective system for studying the basic mechanisms of action of several important secretagogues in the rat."}
{"id": "PMID:238225", "title": "Isolation and structure assignment of an antimicrobial principle from the volatile oil of Nigella sativa L. seeds.", "content": "Refrigeration of the volatile oil of Nigella sativa L. seeds eventuates in a crystalline substance. The chemical structure of the compound was drawn from its chemical behaviour, as well as from its UV, IR, PMR and mass spectral data. The compound was found to be thymohydroquinone: confirmation of the structure was established via the preparation of its corresponding diacetate ester. The compound was found to have high antimicrobial effect against gram positive microorganisms", "contents": "Isolation and structure assignment of an antimicrobial principle from the volatile oil of Nigella sativa L. seeds. Refrigeration of the volatile oil of Nigella sativa L. seeds eventuates in a crystalline substance. The chemical structure of the compound was drawn from its chemical behaviour, as well as from its UV, IR, PMR and mass spectral data. The compound was found to be thymohydroquinone: confirmation of the structure was established via the preparation of its corresponding diacetate ester. The compound was found to have high antimicrobial effect against gram positive microorganisms"}
{"id": "PMID:238221", "title": "Intensification of central catecholaminergin and serotonergic processes by the hypothalamic factors MIF and TRF and by angiotensin II.", "content": "The  present work deals with the action of MIF (melanocyte stimulating hormone release-inhibiting factor), TRF (thyrotropin  releasing factor), and angiotensin II on the behavioral effects of L-DOPA and of D, L-5-hydroxytrytophan (5-HTP) in mice. The influence of MIF and TRF on the antagonistic effect of L-DOPA of harmine tremors in rabbits was also studied. MIF and TRF, injected i.p., intensify the effects of L-DOPA in mice. The minimal dose of MIF required to induce a +3 response is 0.1 microgram/kg; TRF is active at 500 micrograms/kg. When MIF or TRF are injected into the brain, potentiation of L-DOPA is obtained with exceedingly small quantities of MIF (0.1 pg); the effective dose of TRF is 1 microgram. The behavioral effects of 5-HTP are potentiated by TRF only, at doses of 0.1 microgram/kg, i.p. When TRF is administered intracerebrally, the active dose per mouse is 0.1 ng. Harmine (5 mg/kg i.v.) induced, in the rabbit, sustained whole body tremors; if L-DOPA (5 mg/kg) is  administered i.v. at the peak of the harmine effect, tremors subside. When the rabbit is pretreated with MIF administered i.p. 1 -2 hr before harmine, in doses devoid of an antitumor effect per se (10 micrograms/kg), the L-DOPA antagonism appears at lower dose. Also dopamine (5-10 mg/kg i,v.) proved effective in abating harmine tremors; previous treatment with MIF (50 micrograms/kg) potentiated the antagonistic effect of dopamine. According to the prevailing theories on the mechanism of neurotransmission, some hypotheses will be discussed to explain the observed potentiation: impaired uptake, impaired degradation, interference with the turnover of the boiamines, supersensitivity of the receptors.", "contents": "Intensification of central catecholaminergin and serotonergic processes by the hypothalamic factors MIF and TRF and by angiotensin II. The  present work deals with the action of MIF (melanocyte stimulating hormone release-inhibiting factor), TRF (thyrotropin  releasing factor), and angiotensin II on the behavioral effects of L-DOPA and of D, L-5-hydroxytrytophan (5-HTP) in mice. The influence of MIF and TRF on the antagonistic effect of L-DOPA of harmine tremors in rabbits was also studied. MIF and TRF, injected i.p., intensify the effects of L-DOPA in mice. The minimal dose of MIF required to induce a +3 response is 0.1 microgram/kg; TRF is active at 500 micrograms/kg. When MIF or TRF are injected into the brain, potentiation of L-DOPA is obtained with exceedingly small quantities of MIF (0.1 pg); the effective dose of TRF is 1 microgram. The behavioral effects of 5-HTP are potentiated by TRF only, at doses of 0.1 microgram/kg, i.p. When TRF is administered intracerebrally, the active dose per mouse is 0.1 ng. Harmine (5 mg/kg i.v.) induced, in the rabbit, sustained whole body tremors; if L-DOPA (5 mg/kg) is  administered i.v. at the peak of the harmine effect, tremors subside. When the rabbit is pretreated with MIF administered i.p. 1 -2 hr before harmine, in doses devoid of an antitumor effect per se (10 micrograms/kg), the L-DOPA antagonism appears at lower dose. Also dopamine (5-10 mg/kg i,v.) proved effective in abating harmine tremors; previous treatment with MIF (50 micrograms/kg) potentiated the antagonistic effect of dopamine. According to the prevailing theories on the mechanism of neurotransmission, some hypotheses will be discussed to explain the observed potentiation: impaired uptake, impaired degradation, interference with the turnover of the boiamines, supersensitivity of the receptors."}
{"id": "PMID:238228", "title": "Blood pressure response to both carotid occlucion and asphyxia, as influenced by intracerebroventricular injection of norepinephrine or epinephrine.", "content": "The carotid occlusion response (COR) in dogs was inhibited by 50 and 58% after intracerebroventricular injection of norepinephrine and hydrochloric acid, both at the pH 2.9. After norepinephrine at pH 7, this inhibition was 22%. The COR inhibition was 24% with epinephrine solution of pH 2.4 whereas the same solution at pH 7 produced no inhibition. The injection of drugs solved in acid solution, lead to a decrease in the pH of the cerebrospinal fluid. The response to asphyxia was inhibited by 50% after injection of norepinephrine at pH 2.9, but not after epinephrine at pH 2.4 or hydrochloric acid. Bradycardia was caused by epinephrine in neutral or acid solution and a decrease of arterial blood pressure was seen after epinephrine or norepinephrine in neutral or acid solution.", "contents": "Blood pressure response to both carotid occlucion and asphyxia, as influenced by intracerebroventricular injection of norepinephrine or epinephrine. The carotid occlusion response (COR) in dogs was inhibited by 50 and 58% after intracerebroventricular injection of norepinephrine and hydrochloric acid, both at the pH 2.9. After norepinephrine at pH 7, this inhibition was 22%. The COR inhibition was 24% with epinephrine solution of pH 2.4 whereas the same solution at pH 7 produced no inhibition. The injection of drugs solved in acid solution, lead to a decrease in the pH of the cerebrospinal fluid. The response to asphyxia was inhibited by 50% after injection of norepinephrine at pH 2.9, but not after epinephrine at pH 2.4 or hydrochloric acid. Bradycardia was caused by epinephrine in neutral or acid solution and a decrease of arterial blood pressure was seen after epinephrine or norepinephrine in neutral or acid solution."}
{"id": "PMID:238230", "title": "Negative surface charge near sodium channels of nerve: divalent ions, monovalent ions, and pH.", "content": "Evidence is given for a high density of negative surface charge near the sodium channel of myelinated nerve fibres. The voltage dependence of peak sodium permeability is measured in a voltage clamp. The object is to measure voltage shifts in sodium activation as the following external variables are varied: divalent cation concentration and type, monovalent concentration, and pH. With equimolar substitution of divalent ions the order of effectiveness for giving a positive shift is: Ba equals Sr less than Mg less than Ca less than Co approximately equal to Mn less than Ni less than Zn. A tenfold increase of concentration of any of these ions gives a shift of +20 to +25 mV. At low pH, the shift with a tenfold increase in Ca-2+ is much less than at normal pH, and conversely for high pH. Soulutions with no added divalent ions give a shift of minus 18 mV relative to 2 mM Ca-2+. Removal of 7/8 of the cations from the calcium-free solution gives a further shift of minue 35 mV. All shifts are explained quantitatively by assuming that changes in an external surface potential set up by fixed charges near the sodium channel produce the shifts. The model involves a diffuse double layer of counterions at the nerve surface and some binding of H+ions and divalent ions to the fixed charges. Three types of surface groups are postulated: (1) an acid pKa equals 2.88 charge density minus 0.9 nm- minus 2; (i) an acid pKa equals 4.58, charge density minus 0.58 nm- minus 2; (3) a base pKa equals 6.28, charge density +0.33 nm- minus 2. The two acid groups also bind Ca-2+ ions with a dissociation constant K equals 28 M. Reasonable agreement can also be obtained with a lower net surface charge density and stronger binding of divalent ions and H+ ions.", "contents": "Negative surface charge near sodium channels of nerve: divalent ions, monovalent ions, and pH. Evidence is given for a high density of negative surface charge near the sodium channel of myelinated nerve fibres. The voltage dependence of peak sodium permeability is measured in a voltage clamp. The object is to measure voltage shifts in sodium activation as the following external variables are varied: divalent cation concentration and type, monovalent concentration, and pH. With equimolar substitution of divalent ions the order of effectiveness for giving a positive shift is: Ba equals Sr less than Mg less than Ca less than Co approximately equal to Mn less than Ni less than Zn. A tenfold increase of concentration of any of these ions gives a shift of +20 to +25 mV. At low pH, the shift with a tenfold increase in Ca-2+ is much less than at normal pH, and conversely for high pH. Soulutions with no added divalent ions give a shift of minus 18 mV relative to 2 mM Ca-2+. Removal of 7/8 of the cations from the calcium-free solution gives a further shift of minue 35 mV. All shifts are explained quantitatively by assuming that changes in an external surface potential set up by fixed charges near the sodium channel produce the shifts. The model involves a diffuse double layer of counterions at the nerve surface and some binding of H+ions and divalent ions to the fixed charges. Three types of surface groups are postulated: (1) an acid pKa equals 2.88 charge density minus 0.9 nm- minus 2; (i) an acid pKa equals 4.58, charge density minus 0.58 nm- minus 2; (3) a base pKa equals 6.28, charge density +0.33 nm- minus 2. The two acid groups also bind Ca-2+ ions with a dissociation constant K equals 28 M. Reasonable agreement can also be obtained with a lower net surface charge density and stronger binding of divalent ions and H+ ions."}
{"id": "PMID:238231", "title": "Binding of tetrodotoxin and saxitoxin to sodium channels.", "content": "A useful first step in any chemical characterization of the sodium channels in nerve membrane would clearly be the identification of some measurable property of the channel that does not depend on the intactness of the tissue. To this end, tetrodotoxin and saxitoxin, which bind specifically to sodium channels, have been triated and their binding to rabbit, lobster and garfish non-lyelinated nerve fibres examined. In each case, a component of the binding curve was found that saturated at concentrations of a few nanomolar. In addition, non-specific binding, indicated by a linear dependence of the amount bound on concentration, occurred. A solubilized membrane preparation from garfish nerve shows the same specific binding component as that of the intact nerve. The saturable component of binding seems to reflect the sodium channel density in nerve, and this is extremely small, being about 27/mum-2 in the rabbit nerve and as small as 6/mum-2 in the garfish nerve.", "contents": "Binding of tetrodotoxin and saxitoxin to sodium channels. A useful first step in any chemical characterization of the sodium channels in nerve membrane would clearly be the identification of some measurable property of the channel that does not depend on the intactness of the tissue. To this end, tetrodotoxin and saxitoxin, which bind specifically to sodium channels, have been triated and their binding to rabbit, lobster and garfish non-lyelinated nerve fibres examined. In each case, a component of the binding curve was found that saturated at concentrations of a few nanomolar. In addition, non-specific binding, indicated by a linear dependence of the amount bound on concentration, occurred. A solubilized membrane preparation from garfish nerve shows the same specific binding component as that of the intact nerve. The saturable component of binding seems to reflect the sodium channel density in nerve, and this is extremely small, being about 27/mum-2 in the rabbit nerve and as small as 6/mum-2 in the garfish nerve."}
{"id": "PMID:238232", "title": "The purity of tritiated tetrodotoxin as determined by bioassay.", "content": "The radioactivity binding of a tritiated tetrodotoxin preparation to an electric organ particulate fraction was compared with the binding of biological activity as determined by biological assay. This comparison shows that the chromatographically homogeneous toxin contained a large proportion of radioactive impurities which bind nonspecifically to the electroplax preparation.", "contents": "The purity of tritiated tetrodotoxin as determined by bioassay. The radioactivity binding of a tritiated tetrodotoxin preparation to an electric organ particulate fraction was compared with the binding of biological activity as determined by biological assay. This comparison shows that the chromatographically homogeneous toxin contained a large proportion of radioactive impurities which bind nonspecifically to the electroplax preparation."}
{"id": "PMID:238233", "title": "The binding of tritiated tetrodotoxin to squid giant axons.", "content": "The binding of tetrodotoxin to squid gian axons was determined as a function of toxin concentration, using a tritiated toxin preparation of known radiochemical purity and specific activity. From the amount of saturable binding observed, the number of toxin binding sites thought to be sodium channels was found to be 553 plus or minus 119/mum-2 of axon surface.", "contents": "The binding of tritiated tetrodotoxin to squid giant axons. The binding of tetrodotoxin to squid gian axons was determined as a function of toxin concentration, using a tritiated toxin preparation of known radiochemical purity and specific activity. From the amount of saturable binding observed, the number of toxin binding sites thought to be sodium channels was found to be 553 plus or minus 119/mum-2 of axon surface."}
{"id": "PMID:238234", "title": "The reaction between tetrodotoxin and membrane sites at the node of Ranvier: its kinetics and dependence on pH.", "content": "Voltage clamp experiments were done on single nodes of Ranvier to study the inhibition of the sodium permeability by tetrodotoxin (TTX). Equilibrium results could be excellently fitted on the assumption that a sodium channel is blocked when one toxin molecule binds to it, the equilibrium dissociation constant, KT of this reaction being 3.6 nm at 20 degrees C. Onset and offset of block could be quantitatively interpreted to be determined by the rates of the TTX-channel reaction whose average constants, at room temperature, were 3 times 10-6M-minus 1s-minus 1 for the association (k1) and 1.4 times 10-minus 2 s-minus 1 for the dissociation (k2). The dependence of the constants on temperature could be described by Arrhenius plots yielding activation energies of 29.3, 85.5 and 41.0 (57.3) kJ/mol for KT, k2 and k1 (K1 derived from onset alone), respectively. At low pH the relative TTX effect was clearly less than at neutral pH. These results could be explained by a model involving the competition of TTX and protons for the same receptor to which protons bind as a function of membrane potential.", "contents": "The reaction between tetrodotoxin and membrane sites at the node of Ranvier: its kinetics and dependence on pH. Voltage clamp experiments were done on single nodes of Ranvier to study the inhibition of the sodium permeability by tetrodotoxin (TTX). Equilibrium results could be excellently fitted on the assumption that a sodium channel is blocked when one toxin molecule binds to it, the equilibrium dissociation constant, KT of this reaction being 3.6 nm at 20 degrees C. Onset and offset of block could be quantitatively interpreted to be determined by the rates of the TTX-channel reaction whose average constants, at room temperature, were 3 times 10-6M-minus 1s-minus 1 for the association (k1) and 1.4 times 10-minus 2 s-minus 1 for the dissociation (k2). The dependence of the constants on temperature could be described by Arrhenius plots yielding activation energies of 29.3, 85.5 and 41.0 (57.3) kJ/mol for KT, k2 and k1 (K1 derived from onset alone), respectively. At low pH the relative TTX effect was clearly less than at neutral pH. These results could be explained by a model involving the competition of TTX and protons for the same receptor to which protons bind as a function of membrane potential."}
{"id": "PMID:238235", "title": "The rate of action of tetrodotoxin on sodium conductance in the squid giant axon.", "content": "When tetrodotoxin is applied to or washed away from the squid giant axon, the rates at which the sodium conductatnce is blocked and unblocked are an order of magnitude smaller than those reported for the isolated node of Ranvier. This slowing is to be expected if in squid the tetrodotoxin binding sites act as a saturable sink in series with the barrier to free diffusion imposed by the presence of the Schwann cell. A comparison has been made between the rates observed experimentally and those calculated for a computer model of the system, in order to estimate the apparent density in the membrane of both specific and non-specific tetrodotoxin binding sites. The figure thus obtained for the number of sodium channels in the squid giant axon, several hundred per square micrometre, agrees well with those derived from other lines of argument.", "contents": "The rate of action of tetrodotoxin on sodium conductance in the squid giant axon. When tetrodotoxin is applied to or washed away from the squid giant axon, the rates at which the sodium conductatnce is blocked and unblocked are an order of magnitude smaller than those reported for the isolated node of Ranvier. This slowing is to be expected if in squid the tetrodotoxin binding sites act as a saturable sink in series with the barrier to free diffusion imposed by the presence of the Schwann cell. A comparison has been made between the rates observed experimentally and those calculated for a computer model of the system, in order to estimate the apparent density in the membrane of both specific and non-specific tetrodotoxin binding sites. The figure thus obtained for the number of sodium channels in the squid giant axon, several hundred per square micrometre, agrees well with those derived from other lines of argument."}
{"id": "PMID:238236", "title": "Calcium currents in squid giant axon.", "content": "Voltage-clamp experiments were carried out on intracellularly perfused squid giant axons in a Na-free solution of 100 mM CaCl2+sucrose. The internal solution was 25 mM CsF+sucrose or 100 mM RbF+50mM tetraethylammonium chloride+sucrose. Depolarizing voltage clamp steps produced small inward currents; at large depolarizations the inward current reversed into an outward current. Tetrodotoxin completely blocked the inward current and part of the outward current. No inward current was seen with 100 mM MgCl2+sucrose as internal solution. It is concluded that the inward current is carried by Ca ions moving through the sodium channel. The reversal potential of the tetrodotoxin-sensitive current was +54mV with 25 mM CsF+sucrose inside and +10 mV with 100 mM RbF+50 mM tetraethylammonium chloride+sucrose inside. From the reversal potentials measured with varying external and internal solutions the relative permeabilities of the sodium channel for Ca, Cs and Na were calculated by means of the constant field equations. The results of the voltage-clamp experiments are compared with measurements of the Ca entry in intact axons.", "contents": "Calcium currents in squid giant axon. Voltage-clamp experiments were carried out on intracellularly perfused squid giant axons in a Na-free solution of 100 mM CaCl2+sucrose. The internal solution was 25 mM CsF+sucrose or 100 mM RbF+50mM tetraethylammonium chloride+sucrose. Depolarizing voltage clamp steps produced small inward currents; at large depolarizations the inward current reversed into an outward current. Tetrodotoxin completely blocked the inward current and part of the outward current. No inward current was seen with 100 mM MgCl2+sucrose as internal solution. It is concluded that the inward current is carried by Ca ions moving through the sodium channel. The reversal potential of the tetrodotoxin-sensitive current was +54mV with 25 mM CsF+sucrose inside and +10 mV with 100 mM RbF+50 mM tetraethylammonium chloride+sucrose inside. From the reversal potentials measured with varying external and internal solutions the relative permeabilities of the sodium channel for Ca, Cs and Na were calculated by means of the constant field equations. The results of the voltage-clamp experiments are compared with measurements of the Ca entry in intact axons."}
{"id": "PMID:238237", "title": "Voltage-dependent changes in the permeability of nerve membranes to calcium and other divalent cations.", "content": "Transmitter release from depolarized nerve terminals seems to be preceded by a rise in the intracellular concentration of ionized calcium. In squid giant axons, depolarization promotes calcium entry by two routes: one that is blocked by tetrodotoxin and one that is insensitive to tetrodotoxin. The TTX-sensitive route seems to be the sodium channel of the action potential; but the TTX-insensitive route seems to be quite distinct from the sodium and potassium channels of the action potential. It is blocked by Mg-2+, Mn-2+ and Co-2+ ions and by the organic calcium antagonist D-600 and has many features in common with the mechanism that couples excitation to secretion.", "contents": "Voltage-dependent changes in the permeability of nerve membranes to calcium and other divalent cations. Transmitter release from depolarized nerve terminals seems to be preceded by a rise in the intracellular concentration of ionized calcium. In squid giant axons, depolarization promotes calcium entry by two routes: one that is blocked by tetrodotoxin and one that is insensitive to tetrodotoxin. The TTX-sensitive route seems to be the sodium channel of the action potential; but the TTX-insensitive route seems to be quite distinct from the sodium and potassium channels of the action potential. It is blocked by Mg-2+, Mn-2+ and Co-2+ ions and by the organic calcium antagonist D-600 and has many features in common with the mechanism that couples excitation to secretion."}
{"id": "PMID:238238", "title": "The optical spike.", "content": "Among the signs of activity in excitable membranes, the action current (electrical spike) has been extensively studied. Recently, a new approach with optical methods has been rewarding. In nerves, a transient, rapid change of light scanning, birefringence and induced fluorescence can be observed during the passage of the action current. These optical effects are synchronous with the electrical spike and are therefore called the optical spikes. Birefringence decreases during excitation in the giant axon of the squid, the walking nerves of Maia, the vagus nerve of the rabbit, but it increases in the olfactory nerve of the pike, which contains 4 million nonmedullated nerve fibres. Light scattering increases or decreases depending on the angle of observation. Vitally stained nerves with fluorescent probes show an increase and a shift in the wavelength distribution of the fluorescent spike.", "contents": "The optical spike. Among the signs of activity in excitable membranes, the action current (electrical spike) has been extensively studied. Recently, a new approach with optical methods has been rewarding. In nerves, a transient, rapid change of light scanning, birefringence and induced fluorescence can be observed during the passage of the action current. These optical effects are synchronous with the electrical spike and are therefore called the optical spikes. Birefringence decreases during excitation in the giant axon of the squid, the walking nerves of Maia, the vagus nerve of the rabbit, but it increases in the olfactory nerve of the pike, which contains 4 million nonmedullated nerve fibres. Light scattering increases or decreases depending on the angle of observation. Vitally stained nerves with fluorescent probes show an increase and a shift in the wavelength distribution of the fluorescent spike."}
{"id": "PMID:238239", "title": "Heat production non-myelinated nerves.", "content": "Experiments with the C fibres of the rabbit vagus nerve have established that heat is evolved during the depolarizing phase of the action potential and is absorbed during the repolarizing phase. Subsequent studies using the pike olfactory nerve indicate that the heat production begins at a high rate very early in the depolarizing phase and is completed in advance of the peak of the spike. This would be expected if the heat arised from the energy released by the discharge of the membrane capacitance which varies as the square of the membrane potential; but estimates of the stored energy fall short of the observed heat production by a factor of two or three times. The prominent cooling phase suggests that a substantial part of the heat may arise from an entropy change. Such an entropy change would be expected to result from the change in the electrical stress in the dielectric of the membrane capacitance, and may thus be manifestation of reversible changes in the molecular architecture of the insulating matrix of the membrane.", "contents": "Heat production non-myelinated nerves. Experiments with the C fibres of the rabbit vagus nerve have established that heat is evolved during the depolarizing phase of the action potential and is absorbed during the repolarizing phase. Subsequent studies using the pike olfactory nerve indicate that the heat production begins at a high rate very early in the depolarizing phase and is completed in advance of the peak of the spike. This would be expected if the heat arised from the energy released by the discharge of the membrane capacitance which varies as the square of the membrane potential; but estimates of the stored energy fall short of the observed heat production by a factor of two or three times. The prominent cooling phase suggests that a substantial part of the heat may arise from an entropy change. Such an entropy change would be expected to result from the change in the electrical stress in the dielectric of the membrane capacitance, and may thus be manifestation of reversible changes in the molecular architecture of the insulating matrix of the membrane."}
{"id": "PMID:238240", "title": "Potential-dependent conductances in lipid membranes containing alamethicin.", "content": "This article is concerned primarily with the mechanism of the potential-dependent conductance induced in artificial lipid membranes by the cyclic polypeptide andibiotic alamethicin. It has already been shown from studies of the fluctuations that can be detected in very small membrane currents that alamethicin forms transient pores of some 0.6 nm in diameter and that, for small inorganic ions, these are poorly selective. The origin of these pores, their spatial distribution and interaction are discussed. It is demonstrated that the sensitivity of the membrane conductance to the applied potential arises only to a slight extent from the current-voltage relations for the individual pores, and that the main effect stems from the influence of the potential on the frequency of opening of the pores. From the properties of lipid membranes containing alamethicin in a wide variety of electrolytes, and from other evidence, it is concluded that the polypeptide reacts to the electric field more probably because it has dipole moment than because it binds ions. It is proposed that the conducting complex is capable of functioning in either of two orientations, and that it is these two possibilities that give rise to certain differences in the single channel characteristics for the two directions of the field.", "contents": "Potential-dependent conductances in lipid membranes containing alamethicin. This article is concerned primarily with the mechanism of the potential-dependent conductance induced in artificial lipid membranes by the cyclic polypeptide andibiotic alamethicin. It has already been shown from studies of the fluctuations that can be detected in very small membrane currents that alamethicin forms transient pores of some 0.6 nm in diameter and that, for small inorganic ions, these are poorly selective. The origin of these pores, their spatial distribution and interaction are discussed. It is demonstrated that the sensitivity of the membrane conductance to the applied potential arises only to a slight extent from the current-voltage relations for the individual pores, and that the main effect stems from the influence of the potential on the frequency of opening of the pores. From the properties of lipid membranes containing alamethicin in a wide variety of electrolytes, and from other evidence, it is concluded that the polypeptide reacts to the electric field more probably because it has dipole moment than because it binds ions. It is proposed that the conducting complex is capable of functioning in either of two orientations, and that it is these two possibilities that give rise to certain differences in the single channel characteristics for the two directions of the field."}
{"id": "PMID:238241", "title": "Kinetic properties and inactivation of the gating currents of sodium channels in squid axon.", "content": "Associated with the opening and closing of the sodium channels of nerve membrane is a small component of capacitative current, the gating current. After termination of a depolarizing step the gating current and sodium current decay with similar time courses. Both currents decay more rapidly at relatively negative membrane voltages than at positive ones. The gating current that flows during a depolarizing step is diminished by a pre-pulse that inactivates the sodium permeability. A pre-pulse has no effect after inactivation has been destroyed by internal perfusion with the proteolytic enzyme pronase. Gating charge (considered as positive charge) moves outward during a positive voltage step, with voltage dependent kinetics. The time constant of the outward gating current is a maximum at about minus 10 mV, and has a smaller value at voltages either more positive or negative than this value.", "contents": "Kinetic properties and inactivation of the gating currents of sodium channels in squid axon. Associated with the opening and closing of the sodium channels of nerve membrane is a small component of capacitative current, the gating current. After termination of a depolarizing step the gating current and sodium current decay with similar time courses. Both currents decay more rapidly at relatively negative membrane voltages than at positive ones. The gating current that flows during a depolarizing step is diminished by a pre-pulse that inactivates the sodium permeability. A pre-pulse has no effect after inactivation has been destroyed by internal perfusion with the proteolytic enzyme pronase. Gating charge (considered as positive charge) moves outward during a positive voltage step, with voltage dependent kinetics. The time constant of the outward gating current is a maximum at about minus 10 mV, and has a smaller value at voltages either more positive or negative than this value."}
{"id": "PMID:238242", "title": "On the relation between displacement currents and activation of the sodium conductance in the squid giant axon.", "content": "The early time course of the current passing across the membrane in squid giant axons in which the ionic currents have been blocked reveals substantial asymmetries during and after the application of hyperpolarizing and depolarizing voltage-clamp pulses of identical size. Since the integral of the 'on' and 'off' current transients is zero, these currents must result from charge movements confined to the membrane and, therefore, they are nonlinear displacement currents. The steady state rearrangement of the charges as a consequence of sudden displacements of the membrane potential is consistent with a Boltzmann distribution of charges between two states characterized by different energy levels. Following changes in membrane potential the charges undergo a first order transition between these states. The relaxation time constant for the transition at a given temperature is a function of membrane potential. We propose that these displacement currents arise from a redistribution of the charges involved in the sodium gating system.", "contents": "On the relation between displacement currents and activation of the sodium conductance in the squid giant axon. The early time course of the current passing across the membrane in squid giant axons in which the ionic currents have been blocked reveals substantial asymmetries during and after the application of hyperpolarizing and depolarizing voltage-clamp pulses of identical size. Since the integral of the 'on' and 'off' current transients is zero, these currents must result from charge movements confined to the membrane and, therefore, they are nonlinear displacement currents. The steady state rearrangement of the charges as a consequence of sudden displacements of the membrane potential is consistent with a Boltzmann distribution of charges between two states characterized by different energy levels. Following changes in membrane potential the charges undergo a first order transition between these states. The relaxation time constant for the transition at a given temperature is a function of membrane potential. We propose that these displacement currents arise from a redistribution of the charges involved in the sodium gating system."}
{"id": "PMID:238243", "title": "Gating currents in the node of Ranvier: voltage and time dependence.", "content": "Like the axolemma of the giant nerve fibre of the squid, the nodal membrane of frog myelinated nerve fibres after blocking transmembrane ionic currents exhibits asymmetrical displacement currents during and after hyperpolarizing and depolarizing voltage clamp pulses of equal size. The steady-state distribution of charges as a function of membrane potential is consistent with Boltzmanns law (midpoint potential minus 33.7 mV; saturation value 17200 charges/mum-2). The time course of the asymmetry current and the voltage dependence of its time constant are consistent with the notion that due to a sudden change in membrane potential the charges undergo a first order transition between two configurations. Size and voltage dependence of the time constant are similar to those of the activation of the sodium conductance assuming m-2h kinetics. The results suggest that the presence of ten times more sodium channels (5000/mum-2) in the node of Ranvier than in the squid giant axon with similar sodium conductance per channel (2-3 pS).", "contents": "Gating currents in the node of Ranvier: voltage and time dependence. Like the axolemma of the giant nerve fibre of the squid, the nodal membrane of frog myelinated nerve fibres after blocking transmembrane ionic currents exhibits asymmetrical displacement currents during and after hyperpolarizing and depolarizing voltage clamp pulses of equal size. The steady-state distribution of charges as a function of membrane potential is consistent with Boltzmanns law (midpoint potential minus 33.7 mV; saturation value 17200 charges/mum-2). The time course of the asymmetry current and the voltage dependence of its time constant are consistent with the notion that due to a sudden change in membrane potential the charges undergo a first order transition between two configurations. Size and voltage dependence of the time constant are similar to those of the activation of the sodium conductance assuming m-2h kinetics. The results suggest that the presence of ten times more sodium channels (5000/mum-2) in the node of Ranvier than in the squid giant axon with similar sodium conductance per channel (2-3 pS)."}
{"id": "PMID:238244", "title": "Asymmetry currents in intracellularly perfused squid giant axons.", "content": "Asymmetry currents were recorded from intracellularly perfused squid axons subjected to exactly equal positive and negative voltage clamp pulses at a temperature close to 0 degrees C. The voltage and time dependence of the asymmetry currents was studied at a holding potential of minus 80 to minus 100 mV. The effect of varying the holding potential was investigated. The latter experiments showed that the voltage dependence of the asymmetrical charge movement is different from the voltage dependence of the m system.", "contents": "Asymmetry currents in intracellularly perfused squid giant axons. Asymmetry currents were recorded from intracellularly perfused squid axons subjected to exactly equal positive and negative voltage clamp pulses at a temperature close to 0 degrees C. The voltage and time dependence of the asymmetry currents was studied at a holding potential of minus 80 to minus 100 mV. The effect of varying the holding potential was investigated. The latter experiments showed that the voltage dependence of the asymmetrical charge movement is different from the voltage dependence of the m system."}
{"id": "PMID:238245", "title": "Charge movements in skeletal muscle.", "content": "In twitch muscle, an action potential propagating along the surface can lead to mechanical contraction of the entire cross section of the fibre. The processes involve a depolarization of the membranes of the transverse tubular system which, in turn, causes a release of calcium from its intracellular storage location, the sarcoplasmic reticulum. It seems that a change in potential across the first structure can trigger the release from the second, adjacent structure. If the time and voltage dependent ionic currents are blocked, small movements of charge can be detected when a fibre is depolarized from a normal resting potential to a potential at which contraction is activated. These charge movements, which do not behave as currents passing through ionic channels, may be part of a trigger mechanism.", "contents": "Charge movements in skeletal muscle. In twitch muscle, an action potential propagating along the surface can lead to mechanical contraction of the entire cross section of the fibre. The processes involve a depolarization of the membranes of the transverse tubular system which, in turn, causes a release of calcium from its intracellular storage location, the sarcoplasmic reticulum. It seems that a change in potential across the first structure can trigger the release from the second, adjacent structure. If the time and voltage dependent ionic currents are blocked, small movements of charge can be detected when a fibre is depolarized from a normal resting potential to a potential at which contraction is activated. These charge movements, which do not behave as currents passing through ionic channels, may be part of a trigger mechanism."}
{"id": "PMID:238246", "title": "Observations on intramembrane charge movements in skeletal muscle.", "content": "Using signal-averaging techniques, one can record small membrane currents which remain even after blockage of the ionic currents which accompany electrical excitation in muscle. These residual currents probably represent the reorientation of charged molecules inside the membrane in response to a change in membrane potential. Two operationally separable types of intramembrane charge movement in muscle are described, one of which may play a role in excitation-contraction coupling. Studies of tetrodotoxin binding to muscle indicate that \"sodium gating current\" is unlikely to contribute significantly to either type of charge movement.", "contents": "Observations on intramembrane charge movements in skeletal muscle. Using signal-averaging techniques, one can record small membrane currents which remain even after blockage of the ionic currents which accompany electrical excitation in muscle. These residual currents probably represent the reorientation of charged molecules inside the membrane in response to a change in membrane potential. Two operationally separable types of intramembrane charge movement in muscle are described, one of which may play a role in excitation-contraction coupling. Studies of tetrodotoxin binding to muscle indicate that \"sodium gating current\" is unlikely to contribute significantly to either type of charge movement."}
{"id": "PMID:238247", "title": "Steady state current rectification in potential clamped nodes of Ranvier (Xenopus laevis).", "content": "The membrane potential in single nodes of Ranvier was changed in rectangular pulse steps while the membrane currents, associated with the potential steps, were measured. Changes were made in the ionic composition of the external and the internal medium. The latter changes were obtained by free diffusion through a cut internode. The steady state currents, described on the basis of potassium and leak permeability, were affected by the solution composition in a characteristic way. Increased inside concentration of sodium and lithium caused a striking rectification of the outward steady state currents at large potential steps. Instantaneous potassium currents in high [K+]o at a second potential step to E approximately equal to minus 80 mV were not affected by [Na+]1. Neither [Na+]o nor [K+]i affected the potential at which this rectification appeared. Increased [K+]o shifted the region for rectification along the potential axis in positive direction. These findings form strict limitations for satisfactory models describing the mechanism for the steady state current in myelinated nerve.", "contents": "Steady state current rectification in potential clamped nodes of Ranvier (Xenopus laevis). The membrane potential in single nodes of Ranvier was changed in rectangular pulse steps while the membrane currents, associated with the potential steps, were measured. Changes were made in the ionic composition of the external and the internal medium. The latter changes were obtained by free diffusion through a cut internode. The steady state currents, described on the basis of potassium and leak permeability, were affected by the solution composition in a characteristic way. Increased inside concentration of sodium and lithium caused a striking rectification of the outward steady state currents at large potential steps. Instantaneous potassium currents in high [K+]o at a second potential step to E approximately equal to minus 80 mV were not affected by [Na+]1. Neither [Na+]o nor [K+]i affected the potential at which this rectification appeared. Increased [K+]o shifted the region for rectification along the potential axis in positive direction. These findings form strict limitations for satisfactory models describing the mechanism for the steady state current in myelinated nerve."}
{"id": "PMID:238248", "title": "Adrenergic control of cardian pacemaker currents.", "content": "Pacemaker activity in atrial muscle and in Purkinje fibres is generated by a time-dependent decay of potassium current that allows the membrane to be depolarized to the threshold for action potential initiation. The kinetics of the pacemaker potassium currents in these two parts of the heart are sufficiently different to indicate that they correspond to different membrane structures. This conclusion is strengthened by the discovery that the mechanisms of acceleration produced by adrenaline are also quite different. In Purkinje fibres, the activation threshold for the potassium current is shifted in a depolarizing direction with no change in maximum amplitude. This voltage shift is adequate by itself to explain the acceleration. In atrial fibres the pacemaker potassium current is increased in amplitude with no shift in threshold. By itself, this action of adrenaline would slow pacemaker activity and the acceleration in this case is dependent on a large increase in the current attributable to calcium ions. The roles of cyclic 3',5'-AMP and of intracellular calcium ions in mediating the pacemaker actions of adrenaline will also be discussed.", "contents": "Adrenergic control of cardian pacemaker currents. Pacemaker activity in atrial muscle and in Purkinje fibres is generated by a time-dependent decay of potassium current that allows the membrane to be depolarized to the threshold for action potential initiation. The kinetics of the pacemaker potassium currents in these two parts of the heart are sufficiently different to indicate that they correspond to different membrane structures. This conclusion is strengthened by the discovery that the mechanisms of acceleration produced by adrenaline are also quite different. In Purkinje fibres, the activation threshold for the potassium current is shifted in a depolarizing direction with no change in maximum amplitude. This voltage shift is adequate by itself to explain the acceleration. In atrial fibres the pacemaker potassium current is increased in amplitude with no shift in threshold. By itself, this action of adrenaline would slow pacemaker activity and the acceleration in this case is dependent on a large increase in the current attributable to calcium ions. The roles of cyclic 3',5'-AMP and of intracellular calcium ions in mediating the pacemaker actions of adrenaline will also be discussed."}
{"id": "PMID:238249", "title": "Fluorescent probes in membrane studies.", "content": "A number of spectroscopic techniques are suitable for studying biological membranes. Of these, fluorescence has the sensitivity and time resolution for following membrane events associated with nerve excitation. In this paper, the nature of the information derived from measurements of the fluorescence properties of externally introduced chromophores in membranes is examined. In particular, the locations of various probes are described on the basis of nuclear magnetic resonance (n.m.r.) experiments in model situations. Then the motional characteristics of the probe molecules (rotation and diffusion) are discussed. Finally experiments designed to relate the detailed observations that can be made in lipid bilayers using n.m.r. and fuorescence measurements to those (more limited in nature) that can be made in membranes are described.", "contents": "Fluorescent probes in membrane studies. A number of spectroscopic techniques are suitable for studying biological membranes. Of these, fluorescence has the sensitivity and time resolution for following membrane events associated with nerve excitation. In this paper, the nature of the information derived from measurements of the fluorescence properties of externally introduced chromophores in membranes is examined. In particular, the locations of various probes are described on the basis of nuclear magnetic resonance (n.m.r.) experiments in model situations. Then the motional characteristics of the probe molecules (rotation and diffusion) are discussed. Finally experiments designed to relate the detailed observations that can be made in lipid bilayers using n.m.r. and fuorescence measurements to those (more limited in nature) that can be made in membranes are described."}
{"id": "PMID:238250", "title": "Acetylcholine receptors.", "content": "Alpha-Bungarotoxin is one of a class of proteins, isolated from snake venoms, which antagonize the action of acetylcholine at vertebrate neuromuscular junctions and 'electroplaques' of electric fish. Alpha-Bungarotoxin blocks acetylcholine action irreversibly and may be labelled with either 125I or 3H. This irreversible binding is used as the basis of an in vitro assay for acetylcholine receptors, whether in intact tissue, membrane fragments or solubilized preparations. Acetylcholine receptors from Torpedo and denervated skeletal muscle have been solutilized and substantially purified using affinity chromatography. The distribution of acetylcholine receptors in several tissues has been determined, and an auto-immune response, induced by injection of purified Torpedo receptors, has been studied.", "contents": "Acetylcholine receptors. Alpha-Bungarotoxin is one of a class of proteins, isolated from snake venoms, which antagonize the action of acetylcholine at vertebrate neuromuscular junctions and 'electroplaques' of electric fish. Alpha-Bungarotoxin blocks acetylcholine action irreversibly and may be labelled with either 125I or 3H. This irreversible binding is used as the basis of an in vitro assay for acetylcholine receptors, whether in intact tissue, membrane fragments or solubilized preparations. Acetylcholine receptors from Torpedo and denervated skeletal muscle have been solutilized and substantially purified using affinity chromatography. The distribution of acetylcholine receptors in several tissues has been determined, and an auto-immune response, induced by injection of purified Torpedo receptors, has been studied."}
{"id": "PMID:238251", "title": "The influence of pH in the medium on degradation of neurohormones by pregnancy serum.", "content": "The authors studied the dynamics of natural substrates of neurohumoral origin (oxytocin and lysine-vasopressin) by the serum of pregnant and nonpregnant women in relation to the pH in the medium, within pH limits of 2.5 to 8. The values obtained in a polarographic study of depression of the complex oxytocin and lysine-vasopressin polarographic wave by pregnancy and non-pregnancy sera and the results of a parallel analysis of free amino acids of the inactivated substrates under the same conditions showed that, apart from deep degradation of the studied substrates at the optimum pH (5.5 minus 8), less pronounced degradation of the molecule at low pH values (3 minus 4,5), i.e. in a non-physiological blood medium, also occurred. On the basis of their results, the authors submit the hypothesis of the existence of oxytocinase isoenzymes and of the probable presence of several peptidases with overlapping specificity.", "contents": "The influence of pH in the medium on degradation of neurohormones by pregnancy serum. The authors studied the dynamics of natural substrates of neurohumoral origin (oxytocin and lysine-vasopressin) by the serum of pregnant and nonpregnant women in relation to the pH in the medium, within pH limits of 2.5 to 8. The values obtained in a polarographic study of depression of the complex oxytocin and lysine-vasopressin polarographic wave by pregnancy and non-pregnancy sera and the results of a parallel analysis of free amino acids of the inactivated substrates under the same conditions showed that, apart from deep degradation of the studied substrates at the optimum pH (5.5 minus 8), less pronounced degradation of the molecule at low pH values (3 minus 4,5), i.e. in a non-physiological blood medium, also occurred. On the basis of their results, the authors submit the hypothesis of the existence of oxytocinase isoenzymes and of the probable presence of several peptidases with overlapping specificity."}
{"id": "PMID:238252", "title": "Development of the cerebrospinal fluid in chick embryos. Physicochemical properties.", "content": "The development of the physicochemical properties of the cerebrospinal fluid (CSF) was studied in chick embryos from the 9th day of incubation up to hatching. Some of these properties were compared with the corresponding blood or blood plasma properties. During the second half of incubation the CSF pressure rose from 13.2 plus or minus 0.18 mm H2O in 9-day-old embryos to 80.7 plus or minus 0.48 mm H2O just prior to hatching. The critical stages of this development were the 13th to 15th and the 19th to 21st day of incubation. In 13- and 15-day-old embryos, CSF pressure fell sharply after the intracerebral injection of ouabain, but in 19-day embryos it was unaffected. Except for the 15th and 19th incubation day, the CSF pH was always lower than the plasma pH. From the 11th day of incubation up to hatching, the CSF pH fell from 7.36 plus or minus 0.002 to 7.2 plus or minus 0.005. On the 11th and 13th day, specific CSF resistance was higher than plasma resistance, whereas from the 17th incubation day it was significantly lower than the plasma value. During the second half of incubation, specific CSF resistance fell from 1.059 times 10(6) to 0.824 times 10(6) omega mm.m(-1). A difference between the D.C. potential of the venous blood and the CSF appeared for the first time in 15-day-old embryos, the CSF being negative in relation to the blood. By the end of the incubation period this potential difference rose to 10.82 times 0.07 mv.", "contents": "Development of the cerebrospinal fluid in chick embryos. Physicochemical properties. The development of the physicochemical properties of the cerebrospinal fluid (CSF) was studied in chick embryos from the 9th day of incubation up to hatching. Some of these properties were compared with the corresponding blood or blood plasma properties. During the second half of incubation the CSF pressure rose from 13.2 plus or minus 0.18 mm H2O in 9-day-old embryos to 80.7 plus or minus 0.48 mm H2O just prior to hatching. The critical stages of this development were the 13th to 15th and the 19th to 21st day of incubation. In 13- and 15-day-old embryos, CSF pressure fell sharply after the intracerebral injection of ouabain, but in 19-day embryos it was unaffected. Except for the 15th and 19th incubation day, the CSF pH was always lower than the plasma pH. From the 11th day of incubation up to hatching, the CSF pH fell from 7.36 plus or minus 0.002 to 7.2 plus or minus 0.005. On the 11th and 13th day, specific CSF resistance was higher than plasma resistance, whereas from the 17th incubation day it was significantly lower than the plasma value. During the second half of incubation, specific CSF resistance fell from 1.059 times 10(6) to 0.824 times 10(6) omega mm.m(-1). A difference between the D.C. potential of the venous blood and the CSF appeared for the first time in 15-day-old embryos, the CSF being negative in relation to the blood. By the end of the incubation period this potential difference rose to 10.82 times 0.07 mv."}
{"id": "PMID:238253", "title": "Separation of mouse spleen haematopoietic cell fractions for transplantation purposes in lethally irradiated mice.", "content": "Mouse cells were fractioned by adherence chromatography on glass beads. The fractionation of spleen cells yielded 5 different fractions, whose transplantation effect was tested by the method of Till and McCulloch. The results of these transplantation tests showed that the chosen form of adherence chromatography was not sufficiently successful, since none of the resultant fractions contained solely colony-forming units (CFU) and in none of them were CFU present in an exeptionally high concentration.", "contents": "Separation of mouse spleen haematopoietic cell fractions for transplantation purposes in lethally irradiated mice. Mouse cells were fractioned by adherence chromatography on glass beads. The fractionation of spleen cells yielded 5 different fractions, whose transplantation effect was tested by the method of Till and McCulloch. The results of these transplantation tests showed that the chosen form of adherence chromatography was not sufficiently successful, since none of the resultant fractions contained solely colony-forming units (CFU) and in none of them were CFU present in an exeptionally high concentration."}
{"id": "PMID:238256", "title": "Clinical and experimental comparison of diazepam, chlorazepate and placebo.", "content": "A double blind clinical evaluation of chlorazepate (dipotassium-7-chloro-5-phenyl-2,2-dihydroxy-3-carboxy-1,2-dihydro-2H-1,4-benzodiazepine), diazepam and placebo on a patient group of young students, mean age 25 years, is reported. Both drugs were significantly better than placebo and according to global assessment chlorazepate was superior to diazepam. An analysis of the main target symptom revealed better effects of chlorazepate on the following items: anxiety, feeling of muscular tension and gastro-intestinal disturbances. With respect to irritability and sleep disturbances both drugs were found to be equally effective. In patients' self-ratings chlorazepate was considered superior to diazepam in giving more alertness and less drowsiness during day time. The results are discussed with reference to EEG-studies and pharmaco-kinetic properties of chlorazepate and diazepam. Performance tests in simulated car-driving by healthy volunteers did not demonstrate any significant difference as compared with placebo. The psychophysiological eeffects, however, are more pronounced after diazepam than after chlorazepate medication.", "contents": "Clinical and experimental comparison of diazepam, chlorazepate and placebo. A double blind clinical evaluation of chlorazepate (dipotassium-7-chloro-5-phenyl-2,2-dihydroxy-3-carboxy-1,2-dihydro-2H-1,4-benzodiazepine), diazepam and placebo on a patient group of young students, mean age 25 years, is reported. Both drugs were significantly better than placebo and according to global assessment chlorazepate was superior to diazepam. An analysis of the main target symptom revealed better effects of chlorazepate on the following items: anxiety, feeling of muscular tension and gastro-intestinal disturbances. With respect to irritability and sleep disturbances both drugs were found to be equally effective. In patients' self-ratings chlorazepate was considered superior to diazepam in giving more alertness and less drowsiness during day time. The results are discussed with reference to EEG-studies and pharmaco-kinetic properties of chlorazepate and diazepam. Performance tests in simulated car-driving by healthy volunteers did not demonstrate any significant difference as compared with placebo. The psychophysiological eeffects, however, are more pronounced after diazepam than after chlorazepate medication."}
{"id": "PMID:238258", "title": "The acute effects of intravenous infusion of parathyroid hormone on urine, plasma and saliva in the sheep.", "content": "Following an intravenous loading injection of 75 U.S.P. Units of Para-Thor-Mone (Eli Lilly and Co), seven conscious, non-pregnant, non-lactating Merino ewes were infused with a maintenance dose of the hormone at a rate of 4-75 U.S.P. units/min for 2 hr. The classical hypercalcaemia and hypophosphataemia of the non-ruminant was observed, but the hypercalcaemi- was only small. Plasma potassium concentration decreases, while there were no changes in plasma sodium, chloride or mangesium. The classical phosphaturic effect of the hormone was not observed, only trace amounts of phosphate being exreted throughout the experiment. Urinary excretion of calcium and magnesium decreased, urine flow and urinary excretion of sodium, potassium, chloride, bicarbonate and urine pH increased. Glomerular filtration rate was unaffected, but renal plasma flow increased. The concentration and secretion rate of salivary phosphate increased markedly. Changes in the other important salivary electrolytes (sodium, potassium, chloride, bicarbonate and hydrogen ion) also occurred, but it was difficult to separate primary from secondary effects of the hormone. Saliva flow rate increased transiently following hormone injection, but the effect was not sustained by the maintenance infusion.", "contents": "The acute effects of intravenous infusion of parathyroid hormone on urine, plasma and saliva in the sheep. Following an intravenous loading injection of 75 U.S.P. Units of Para-Thor-Mone (Eli Lilly and Co), seven conscious, non-pregnant, non-lactating Merino ewes were infused with a maintenance dose of the hormone at a rate of 4-75 U.S.P. units/min for 2 hr. The classical hypercalcaemia and hypophosphataemia of the non-ruminant was observed, but the hypercalcaemi- was only small. Plasma potassium concentration decreases, while there were no changes in plasma sodium, chloride or mangesium. The classical phosphaturic effect of the hormone was not observed, only trace amounts of phosphate being exreted throughout the experiment. Urinary excretion of calcium and magnesium decreased, urine flow and urinary excretion of sodium, potassium, chloride, bicarbonate and urine pH increased. Glomerular filtration rate was unaffected, but renal plasma flow increased. The concentration and secretion rate of salivary phosphate increased markedly. Changes in the other important salivary electrolytes (sodium, potassium, chloride, bicarbonate and hydrogen ion) also occurred, but it was difficult to separate primary from secondary effects of the hormone. Saliva flow rate increased transiently following hormone injection, but the effect was not sustained by the maintenance infusion."}
{"id": "PMID:238264", "title": "Histochemical development of myofibres in neonatal piglets.", "content": "The periodic acid-Schiff (PAS) reaction and tests for glycogen phosphorylase, oxidative enzymes and acid-stable and alkali-stable adenosine triphophatase (ATPase) were used to determine the degree of histochemical differentiation between myofibres of sartorius muscles from neonatal piglets. Within 24 h of birth, the ratio of myofibres with acid-stable ATPase to those with acid-labile ATPase was 1:21-0. By 10 days the ratio had changed to 1:5-2. Mean minimum myofibre diameters (all histochemical types combined) increased steadily after birth although diameters of myofibres with acid-stable ATPase showed no increase until 6 days. By 10 days, consistent differentiation was observed with the alkali-stable ATPase and glycogen phosphorylase reactions but not with the PAS reaction. During the 10 day neonatal period, all types of myofibres contained large or moderate numbers of mitochondria.", "contents": "Histochemical development of myofibres in neonatal piglets. The periodic acid-Schiff (PAS) reaction and tests for glycogen phosphorylase, oxidative enzymes and acid-stable and alkali-stable adenosine triphophatase (ATPase) were used to determine the degree of histochemical differentiation between myofibres of sartorius muscles from neonatal piglets. Within 24 h of birth, the ratio of myofibres with acid-stable ATPase to those with acid-labile ATPase was 1:21-0. By 10 days the ratio had changed to 1:5-2. Mean minimum myofibre diameters (all histochemical types combined) increased steadily after birth although diameters of myofibres with acid-stable ATPase showed no increase until 6 days. By 10 days, consistent differentiation was observed with the alkali-stable ATPase and glycogen phosphorylase reactions but not with the PAS reaction. During the 10 day neonatal period, all types of myofibres contained large or moderate numbers of mitochondria."}
{"id": "PMID:238265", "title": "[Induced beta-adrenergic stimulation and blockade in asthma bronchomotor effects (author's transl)].", "content": "Patients with asthma, exhibiting spontaneous bronchial obstruction, from mild to medium severity, were examined by body plethysmography. Results were expressed as specific airway resistance (SRaw) in preference to specific conductance, the latter leading to errors, in particular in cases with dissimilar baseline values. After the inhalation of a beta-stimulating drug (salbutamol), the decreases in SRaw was directly related to initial SRaw, either in a group (n equal 30) or in individual cases. After the injection of a beta-blocking drug (propranolol), the increase in SRaw, found abnormal in 60% of the subjects, could be related to initial SRaw neither in a group (n equal 40) nor in individual cases. These findings indicate that submaximal bronchial obstruction in patients with asthma is mainly due to a bronchoconstriction, whatever the degree of the obstruction may be. On the opposite, there is an increased bronchodilator adrenergic influence in a majority of patients, not predictable after the degree of initial airway obstruction.", "contents": "[Induced beta-adrenergic stimulation and blockade in asthma bronchomotor effects (author's transl)]. Patients with asthma, exhibiting spontaneous bronchial obstruction, from mild to medium severity, were examined by body plethysmography. Results were expressed as specific airway resistance (SRaw) in preference to specific conductance, the latter leading to errors, in particular in cases with dissimilar baseline values. After the inhalation of a beta-stimulating drug (salbutamol), the decreases in SRaw was directly related to initial SRaw, either in a group (n equal 30) or in individual cases. After the injection of a beta-blocking drug (propranolol), the increase in SRaw, found abnormal in 60% of the subjects, could be related to initial SRaw neither in a group (n equal 40) nor in individual cases. These findings indicate that submaximal bronchial obstruction in patients with asthma is mainly due to a bronchoconstriction, whatever the degree of the obstruction may be. On the opposite, there is an increased bronchodilator adrenergic influence in a majority of patients, not predictable after the degree of initial airway obstruction."}
{"id": "PMID:238266", "title": "The carbamate equilibrium of bovine hemoglobin at 37 degrees C.", "content": "emoglobin-bound CO2 was estimated by a procedure first described by Rossi-Bernardi et al. (1969) in which the carbamate compound is stabilized by rapid mixing with alkali and then separated from other CO2 constituents in solution by gel filtration and ion-exchange chromatography. Carbamate equilibrium of bovine hemoglobin was studied at constant PCO2 (44 mm Hg) and varying pH as well as at constant pH (7.4) and varying PCO2 (ionic strength 0.18, temperature 37.0 degrees C). The difference in Z (deltaZ) between hemoglobin and oxyhemoglobin appeared to be 0.11 plus or minus 0.04 (pH=7.40; PCO2=44 mm Hg) i.e. about half the value observed in human hemoglobin. DeltaZ was shown to account completely for the difference in CO2 content (CCO2) between hemoglobin and oxyhemoglobin when in total equilibrium with CO2. Carbamate determinations on bovine hemoglobin specifically modified at all terminal amino groups (double-blocked carbamylated derivative) did not show any CO2 binding at all, thus giving a final proof for the exclusive role of the terminal amino groups in CO2 binding under physiological conditions. Attempts to calculate the ionization constant (Kz) and the carbamate equilibrium constant (Kc) of the terminal amino groups failed, suggesting that both terminal groups are not equivalent in their CO2 binding properties. This was confirmed by the fact that carbamate data obtained at constant PCO2 and varying pH fitted binding curves derived from two sets of independent but non-equivalent binding sites. Association constants for both kinds of binding sites appeared to differ by a factor of at least 3 in hemoglobin and of about 10 in oxyhemoglobin. From determinations of hemoglobin-bound CO2 and CO2 content of hemoglobin and oxyhemoglobin solutions in total equilibrium with CO2, the apparent first dissociation constant of carbonic acid was calculated as 5.71 plus or minus 0.0061 pH and found to be independent of the oxygenation state of hemoglobin. In contrast with hemoglobin of other species bovine hemoglobin appeared to be not influenced by the presence of 2.3-diphosphoglycerate as far as its CO2-binding properties are concerned.", "contents": "The carbamate equilibrium of bovine hemoglobin at 37 degrees C. emoglobin-bound CO2 was estimated by a procedure first described by Rossi-Bernardi et al. (1969) in which the carbamate compound is stabilized by rapid mixing with alkali and then separated from other CO2 constituents in solution by gel filtration and ion-exchange chromatography. Carbamate equilibrium of bovine hemoglobin was studied at constant PCO2 (44 mm Hg) and varying pH as well as at constant pH (7.4) and varying PCO2 (ionic strength 0.18, temperature 37.0 degrees C). The difference in Z (deltaZ) between hemoglobin and oxyhemoglobin appeared to be 0.11 plus or minus 0.04 (pH=7.40; PCO2=44 mm Hg) i.e. about half the value observed in human hemoglobin. DeltaZ was shown to account completely for the difference in CO2 content (CCO2) between hemoglobin and oxyhemoglobin when in total equilibrium with CO2. Carbamate determinations on bovine hemoglobin specifically modified at all terminal amino groups (double-blocked carbamylated derivative) did not show any CO2 binding at all, thus giving a final proof for the exclusive role of the terminal amino groups in CO2 binding under physiological conditions. Attempts to calculate the ionization constant (Kz) and the carbamate equilibrium constant (Kc) of the terminal amino groups failed, suggesting that both terminal groups are not equivalent in their CO2 binding properties. This was confirmed by the fact that carbamate data obtained at constant PCO2 and varying pH fitted binding curves derived from two sets of independent but non-equivalent binding sites. Association constants for both kinds of binding sites appeared to differ by a factor of at least 3 in hemoglobin and of about 10 in oxyhemoglobin. From determinations of hemoglobin-bound CO2 and CO2 content of hemoglobin and oxyhemoglobin solutions in total equilibrium with CO2, the apparent first dissociation constant of carbonic acid was calculated as 5.71 plus or minus 0.0061 pH and found to be independent of the oxygenation state of hemoglobin. In contrast with hemoglobin of other species bovine hemoglobin appeared to be not influenced by the presence of 2.3-diphosphoglycerate as far as its CO2-binding properties are concerned."}
{"id": "PMID:238267", "title": "Intracellular pH of isolated rat diaphragm muscle with metabolic and respiratory changes of extracellular pH.", "content": "Relationships between intracellular and extracellular pH isolated rat diaphragms were determined both during respiratory and metabolic changes of extracellular pH. Metabolic changes of extracellular pH were produced by varying bicarbonate concentration of the suspending Krebs-Ringer solution and respiratory changes were produced by varying PCO2 of the suspending medium. At any defined extracellular pH, the bicarbonate concentration ratios between intracellular and extracellular space were the same during both metabolic and respiratory changes of extracellular pH. However, when extracellular pH varied within 7.15 and 7.4 intracellular pH remained essentially constant. In order to maintain the intracellular pH constant during extracellular pH changes, a bicarbonate efflux during metabolic changes from the intracellular compartment, and a bicarbonate influx during respiratory changes to the intracellular compartment must occur. The maintenance of identical intracellular/extracellular bicarbonate concentration ratios regardless of the mechanisms of extracellular pH changes (metabolic or respiratory) suggests an active mechanism for the transport of bicarbonate or H-+ ions.", "contents": "Intracellular pH of isolated rat diaphragm muscle with metabolic and respiratory changes of extracellular pH. Relationships between intracellular and extracellular pH isolated rat diaphragms were determined both during respiratory and metabolic changes of extracellular pH. Metabolic changes of extracellular pH were produced by varying bicarbonate concentration of the suspending Krebs-Ringer solution and respiratory changes were produced by varying PCO2 of the suspending medium. At any defined extracellular pH, the bicarbonate concentration ratios between intracellular and extracellular space were the same during both metabolic and respiratory changes of extracellular pH. However, when extracellular pH varied within 7.15 and 7.4 intracellular pH remained essentially constant. In order to maintain the intracellular pH constant during extracellular pH changes, a bicarbonate efflux during metabolic changes from the intracellular compartment, and a bicarbonate influx during respiratory changes to the intracellular compartment must occur. The maintenance of identical intracellular/extracellular bicarbonate concentration ratios regardless of the mechanisms of extracellular pH changes (metabolic or respiratory) suggests an active mechanism for the transport of bicarbonate or H-+ ions."}
{"id": "PMID:238268", "title": "Metabolic changes in avian blood and their effects on determination of blood gases and pH.", "content": "Oxygen consumption. MO2 and CO2 production rates, Cco2, of duck blood samples anaerobically stored at 41 degrees C were 0.041 and 0.036 mMol (L blood)minus 1 min minus 1, respectively, and were independent of O2 saturation in the range of 100 to 10% saturation; the resulting metabolic respiratory quotient of blood was 0.88. The pH decreased linearly with time at a rate of 0.0014 unit min minus 1. The lactic acid production rate was independent of Po2, and was about 0.033 MMol L minus 1 min minus 1. Errors were assessed that may be introduced in blood gas analysis when the high metabolic activity of avian blood is not accounted for. Thus the O2 dissociation curve established using the Van Slyke analysis will be shifted to the right; however, the displacement around P50 is only about 1 torr for a time lag of 5 min between sampling and analysis and is even less at higher Po2 values. When using electrodes, P02 will be underestimated and PCO2 overestimated. The magnitude of these errors depends on both delay time and slope of the dissociation curves. It is concluded that the standard blood gas analytical methods are applicable to avian blood, but that in some cases corrections for metabolic effects are neccessary. Any delay between blood sampling and analysis should be kept as short as possible; storage, if neccessary, should be on ice.", "contents": "Metabolic changes in avian blood and their effects on determination of blood gases and pH. Oxygen consumption. MO2 and CO2 production rates, Cco2, of duck blood samples anaerobically stored at 41 degrees C were 0.041 and 0.036 mMol (L blood)minus 1 min minus 1, respectively, and were independent of O2 saturation in the range of 100 to 10% saturation; the resulting metabolic respiratory quotient of blood was 0.88. The pH decreased linearly with time at a rate of 0.0014 unit min minus 1. The lactic acid production rate was independent of Po2, and was about 0.033 MMol L minus 1 min minus 1. Errors were assessed that may be introduced in blood gas analysis when the high metabolic activity of avian blood is not accounted for. Thus the O2 dissociation curve established using the Van Slyke analysis will be shifted to the right; however, the displacement around P50 is only about 1 torr for a time lag of 5 min between sampling and analysis and is even less at higher Po2 values. When using electrodes, P02 will be underestimated and PCO2 overestimated. The magnitude of these errors depends on both delay time and slope of the dissociation curves. It is concluded that the standard blood gas analytical methods are applicable to avian blood, but that in some cases corrections for metabolic effects are neccessary. Any delay between blood sampling and analysis should be kept as short as possible; storage, if neccessary, should be on ice."}
{"id": "PMID:238269", "title": "The effect of acetazolamide on myocardial carbon dioxide space.", "content": "Carbon dioxide, water and vascular space were measured in the heart muscle of the dog before and after the administration of acetazolamide. In contrast to the skeletal muscle whose CO2 space was markedly reduced by acetazolamide, cardiac muscle CO2 space was only minimally reduced. This suggests that cardiac muscle does not have extravascular carbonic anhydrase. Its presence in skeletal muscle and absence in cardiac muscle probably relates to the differences in cell size between the two types of muscle and their differing degree of vascularity.", "contents": "The effect of acetazolamide on myocardial carbon dioxide space. Carbon dioxide, water and vascular space were measured in the heart muscle of the dog before and after the administration of acetazolamide. In contrast to the skeletal muscle whose CO2 space was markedly reduced by acetazolamide, cardiac muscle CO2 space was only minimally reduced. This suggests that cardiac muscle does not have extravascular carbonic anhydrase. Its presence in skeletal muscle and absence in cardiac muscle probably relates to the differences in cell size between the two types of muscle and their differing degree of vascularity."}
{"id": "PMID:238270", "title": "Arterial blood gases in undisturbed resting birds: measurements in chicken and duck.", "content": "Arterial blood was sampled in resting, unrestrained and undisturbed birds using a remote-controlled sampling device. With this technique a blood sample of 0.45 ml was obtained for analysis of PO2, PCO2 and pH at the body temperature of the animal. In 5 domestic hens the following mean values were obtained: PA02-82 torr; PACO2=33 torr; pHA=7.52. The average body temperature was TB=41.0 degrees C. In 6 domestic ducks the analysis yielded values of PAO2=82 torr; PACO2=38 torr; pH2=7.49; Tb=41.0 degrees C. Although these values are close to those reported in the literature some discrepancies may be recognized; they can be attributed to respiratory and metabolic changes of blood composition possibly induced by classical sampling procedures.", "contents": "Arterial blood gases in undisturbed resting birds: measurements in chicken and duck. Arterial blood was sampled in resting, unrestrained and undisturbed birds using a remote-controlled sampling device. With this technique a blood sample of 0.45 ml was obtained for analysis of PO2, PCO2 and pH at the body temperature of the animal. In 5 domestic hens the following mean values were obtained: PA02-82 torr; PACO2=33 torr; pHA=7.52. The average body temperature was TB=41.0 degrees C. In 6 domestic ducks the analysis yielded values of PAO2=82 torr; PACO2=38 torr; pH2=7.49; Tb=41.0 degrees C. Although these values are close to those reported in the literature some discrepancies may be recognized; they can be attributed to respiratory and metabolic changes of blood composition possibly induced by classical sampling procedures."}
{"id": "PMID:238271", "title": "Blood acid-base changes during experimental emersion and reimmersion of the intertidal crab Carcinus maenas (L.).", "content": "The time course of blood acid-base changes was studied in Carcinus maenas during experimental emersion and reimmersion at 15 degrees C by measuring pH and PCO2 and calculating bicarbonate concentration. During the first 4 hr of the emersion period, a marked rise of PCO2 entails a respiratory acidosis which is progressively compensated by a slow increase of the bicarbonate concentration; this compensation is completed after about 100 hr and the steady state mean pH value approximates that found for the immersed controls. Return to aquatic conditions is characterized by a rapid decrease of both PCO2 and blood bicarbonate concentration. During the first 2 hr of the reimmersion period, the decrease of blood bicarbonate concentration is accompanied by excretion of a significant amount of base in water, thus suggesting that readjustments of acid-base balance take place at least in part by ionic exchanges between the blood and the external milieu. Initial status was restored after 9 hr. These finding agree with the general views concerning the blood acid-base changes which must occur at transition from water-to air-breathing.", "contents": "Blood acid-base changes during experimental emersion and reimmersion of the intertidal crab Carcinus maenas (L.). The time course of blood acid-base changes was studied in Carcinus maenas during experimental emersion and reimmersion at 15 degrees C by measuring pH and PCO2 and calculating bicarbonate concentration. During the first 4 hr of the emersion period, a marked rise of PCO2 entails a respiratory acidosis which is progressively compensated by a slow increase of the bicarbonate concentration; this compensation is completed after about 100 hr and the steady state mean pH value approximates that found for the immersed controls. Return to aquatic conditions is characterized by a rapid decrease of both PCO2 and blood bicarbonate concentration. During the first 2 hr of the reimmersion period, the decrease of blood bicarbonate concentration is accompanied by excretion of a significant amount of base in water, thus suggesting that readjustments of acid-base balance take place at least in part by ionic exchanges between the blood and the external milieu. Initial status was restored after 9 hr. These finding agree with the general views concerning the blood acid-base changes which must occur at transition from water-to air-breathing."}
{"id": "PMID:238272", "title": "Mechanisms of O2 transport in Andean dogs.", "content": "Using previously inserted catheters, 11 dogs native to high altitude (7.5-23 kg bwt) were studied standing and unsedated in Cerro de Pasco, Peru at 4350 meters. Hemoglobin (Hb), hematocrit (Hct), O2 and CO2 contents, PO2, PCO2 and pH were measured in simultaneously obtained arterial and mixed venous blood samples. Blood pressures were measured in the pulmonary artery and the left ventricle and cardiac output (Q) was determined by dye dilution. Moderately higher values for Hb and Hct were found in these dogs. Hb-O2 affinity was no different than that found in sea level dogs: the P50 in the Andean dogs was 31.6 mm Hg at 38 degrees C and pH of 7.4. Because of the low barometric pressure at 4350 m (458 mmHg) the partial pressures of oxygen in inspired and in alveolar air were lower than at sea level: 84.3 and 56.4 mm Hg, respectively. PAO2 and PVO2, were 55.5 and 32.9 mm Hg while the SAO2 and SVO2 were 79.5 and 50.7%, respectively. Marked hyperventilation was observed (PACO2, 25.6 mm Hg) however, pH was normal. Cardiac output was normal (average 162 plus or minus 39 ml/min/kg). Moderate pulmonary arterial hypertension was observed in the presence of normal left ventricular end diastolic pressure suggesting increased pulmonary vascular resistance.", "contents": "Mechanisms of O2 transport in Andean dogs. Using previously inserted catheters, 11 dogs native to high altitude (7.5-23 kg bwt) were studied standing and unsedated in Cerro de Pasco, Peru at 4350 meters. Hemoglobin (Hb), hematocrit (Hct), O2 and CO2 contents, PO2, PCO2 and pH were measured in simultaneously obtained arterial and mixed venous blood samples. Blood pressures were measured in the pulmonary artery and the left ventricle and cardiac output (Q) was determined by dye dilution. Moderately higher values for Hb and Hct were found in these dogs. Hb-O2 affinity was no different than that found in sea level dogs: the P50 in the Andean dogs was 31.6 mm Hg at 38 degrees C and pH of 7.4. Because of the low barometric pressure at 4350 m (458 mmHg) the partial pressures of oxygen in inspired and in alveolar air were lower than at sea level: 84.3 and 56.4 mm Hg, respectively. PAO2 and PVO2, were 55.5 and 32.9 mm Hg while the SAO2 and SVO2 were 79.5 and 50.7%, respectively. Marked hyperventilation was observed (PACO2, 25.6 mm Hg) however, pH was normal. Cardiac output was normal (average 162 plus or minus 39 ml/min/kg). Moderate pulmonary arterial hypertension was observed in the presence of normal left ventricular end diastolic pressure suggesting increased pulmonary vascular resistance."}
{"id": "PMID:238274", "title": "A study of the influence of various antirheumatic drug regimens on serum acute-phase proteins, plasma tryptophan, and erythrocyte sedimentation rate in rheumatoid arthritis.", "content": "In patients with rheumatoid arthritis neither indomethacin nor aspirin influenced the levels of the erythrocyte sedimentation rate (e.s.r) or serum acute-phase proteins fibrinogen, haptoglobin, C-reactive protein and alphaI acid-glycoprotein). Treatment with D-penicillamine, sodium aurothiomalate, or alclofenac produced a significant reduction both in acute-phase protein levels and in e.s.r. Each of the drugs displaced L-tryptophan from plasma proteins in vivo but withdrawal of indomethacin and aspirin was followed immediatley by excessive binding of this amino acid to circulating proteins:this phenomenon was not observed when alclofenac, sodium aurothiomalate or D-penicillamine were withdrawn. It has been demonstrated that disease activity in rheumatoid arthritis is reflected in acute-phase protein concentrations and in the extent to which L-tryptophan is bount to plasma protein. It is suggested that drugs which profoundly affect these parameters provide not only symptomatic relieft but also possible beneficial effects upon the disease process itself.", "contents": "A study of the influence of various antirheumatic drug regimens on serum acute-phase proteins, plasma tryptophan, and erythrocyte sedimentation rate in rheumatoid arthritis. In patients with rheumatoid arthritis neither indomethacin nor aspirin influenced the levels of the erythrocyte sedimentation rate (e.s.r) or serum acute-phase proteins fibrinogen, haptoglobin, C-reactive protein and alphaI acid-glycoprotein). Treatment with D-penicillamine, sodium aurothiomalate, or alclofenac produced a significant reduction both in acute-phase protein levels and in e.s.r. Each of the drugs displaced L-tryptophan from plasma proteins in vivo but withdrawal of indomethacin and aspirin was followed immediatley by excessive binding of this amino acid to circulating proteins:this phenomenon was not observed when alclofenac, sodium aurothiomalate or D-penicillamine were withdrawn. It has been demonstrated that disease activity in rheumatoid arthritis is reflected in acute-phase protein concentrations and in the extent to which L-tryptophan is bount to plasma protein. It is suggested that drugs which profoundly affect these parameters provide not only symptomatic relieft but also possible beneficial effects upon the disease process itself."}
{"id": "PMID:238275", "title": "Comparison of benorylate and ibuprofen in the treatment of established rheumatoid arthritis.", "content": "Benorylate and ibuprofen appear to be useful drugs for pain relief in rheumatoid arthritis but benorylate would appear to have a slightly better effect on the pain score and it improved the grip strength more than the moderate doses of ibuprofen. It could be a most useful drug when gastric problems limit the dose of aspirin or of other analgesics.", "contents": "Comparison of benorylate and ibuprofen in the treatment of established rheumatoid arthritis. Benorylate and ibuprofen appear to be useful drugs for pain relief in rheumatoid arthritis but benorylate would appear to have a slightly better effect on the pain score and it improved the grip strength more than the moderate doses of ibuprofen. It could be a most useful drug when gastric problems limit the dose of aspirin or of other analgesics."}
{"id": "PMID:238279", "title": "Urinary excretion of hydroxyprolines in man under the influence of cold.", "content": "Urinary hydroxyproline excretion was studied in human subjects exposed to cold stress and was related to urine flow and tubular reabsorption of calcium and phosphate. The results indicate the occurrence of a calcium release from the bones, which does not seem to be caused by changed activity or immobilization. The cold-induced changes--calcium excretion, dehydration, and demineralization - are the same as those reported under space-flight conditions. Furthermore, it has also been possible to induce a similar response with psychological stress agents. These findings, together with recent observations on renal stone formation and hyperparathyrodism, indicate that different types of stress might have a direct influence on calcium homeostasis, possibly mediated by the adrenergic nervous system.", "contents": "Urinary excretion of hydroxyprolines in man under the influence of cold. Urinary hydroxyproline excretion was studied in human subjects exposed to cold stress and was related to urine flow and tubular reabsorption of calcium and phosphate. The results indicate the occurrence of a calcium release from the bones, which does not seem to be caused by changed activity or immobilization. The cold-induced changes--calcium excretion, dehydration, and demineralization - are the same as those reported under space-flight conditions. Furthermore, it has also been possible to induce a similar response with psychological stress agents. These findings, together with recent observations on renal stone formation and hyperparathyrodism, indicate that different types of stress might have a direct influence on calcium homeostasis, possibly mediated by the adrenergic nervous system."}
{"id": "PMID:238280", "title": "Antibacterial precipitins and autoantibodies in serum of patients with cystic fibrosis.", "content": "Sera from 84 patients with cystic fibrosis, 31 patients with other respiratory diseases and 21 control persons have been investigated for the occurrence of antibacterial precipitins and autoantibodies. Preciptins were studied by means of crossed immunoelectrophoresis, antinuclear factors by an indirect immunofluorescence technique and rheumatoid factors by the latex fixation slide test. A very heterogeneous antibacterial immune response was found in patients with cystic fibrosis, notably as regards Ps. aeruginosa. None of the other patients or controls had precipitins against this bacterium. The occurrence of precipitins against St. aureus and D. pneumoniae were more frequent in cystic fibrosis patients as compared with controls, but not as compared with other respiratory disease patients. No significant differences were found as regards precipitins against H. influenzae or the occurrence of rheumatoid factors. Antinuclear factors were more frequent in cystic fibrosis patients than in the other two groups investigated. A pronounced and heterogeneous humoral immune response against Ps. aeruginosa in cystic fibrosis patients chronically infected with mucoid strains of this bacterium was found to be correlated with poor prognosis and the reason for this is discussed.", "contents": "Antibacterial precipitins and autoantibodies in serum of patients with cystic fibrosis. Sera from 84 patients with cystic fibrosis, 31 patients with other respiratory diseases and 21 control persons have been investigated for the occurrence of antibacterial precipitins and autoantibodies. Preciptins were studied by means of crossed immunoelectrophoresis, antinuclear factors by an indirect immunofluorescence technique and rheumatoid factors by the latex fixation slide test. A very heterogeneous antibacterial immune response was found in patients with cystic fibrosis, notably as regards Ps. aeruginosa. None of the other patients or controls had precipitins against this bacterium. The occurrence of precipitins against St. aureus and D. pneumoniae were more frequent in cystic fibrosis patients as compared with controls, but not as compared with other respiratory disease patients. No significant differences were found as regards precipitins against H. influenzae or the occurrence of rheumatoid factors. Antinuclear factors were more frequent in cystic fibrosis patients than in the other two groups investigated. A pronounced and heterogeneous humoral immune response against Ps. aeruginosa in cystic fibrosis patients chronically infected with mucoid strains of this bacterium was found to be correlated with poor prognosis and the reason for this is discussed."}
{"id": "PMID:238281", "title": "[Dental plaque pH in patients with hereditary fructose intolerance].", "content": "There is little doubt that the initial cariogenic attack upon dental enamel is caused by acids stemming from metabolic activity of dental plaque microorganisms fermenting carbohydrates. However, a direct correlation between caries activity and pH changes of plaque has not yet been established. In-vio and in-vitro plaque pH was recorded in 4 caries-free HFI children by the method of Graf, R., and Graf, H. Application of 10% glucose were followed regularly by pH drops from the fasting range pH 6.2-7.2) reaching values of 4.7 to 6.5 after 20 minutes. These were comparable to values found in normal subjects. 10% sucrose treatment resulted in a slower and less pronounced pH lowering, reaching a pH between 4.8 and 6.5 compared to normal control subjects, which showed the classical drop down to pH 4.0 to 4.3 The results indicate that human dental plaque grown under sucrose- free conditions cannot metabolize sucrose (or its initial breakdown produce fructose) to produce an in-vivo pH drop below the critical range of enamel demineralization. The zero caries activity of the children may be explained by the lack of a demonstrable classical pH drop or acid attack.", "contents": "[Dental plaque pH in patients with hereditary fructose intolerance]. There is little doubt that the initial cariogenic attack upon dental enamel is caused by acids stemming from metabolic activity of dental plaque microorganisms fermenting carbohydrates. However, a direct correlation between caries activity and pH changes of plaque has not yet been established. In-vio and in-vitro plaque pH was recorded in 4 caries-free HFI children by the method of Graf, R., and Graf, H. Application of 10% glucose were followed regularly by pH drops from the fasting range pH 6.2-7.2) reaching values of 4.7 to 6.5 after 20 minutes. These were comparable to values found in normal subjects. 10% sucrose treatment resulted in a slower and less pronounced pH lowering, reaching a pH between 4.8 and 6.5 compared to normal control subjects, which showed the classical drop down to pH 4.0 to 4.3 The results indicate that human dental plaque grown under sucrose- free conditions cannot metabolize sucrose (or its initial breakdown produce fructose) to produce an in-vivo pH drop below the critical range of enamel demineralization. The zero caries activity of the children may be explained by the lack of a demonstrable classical pH drop or acid attack."}
{"id": "PMID:238284", "title": "Urinary lithiasis in childhood in the Bristol clinical area.", "content": "A series of 59 consecutive cases of urinary calculi in childhood is presented, being acquired from one local area (Bristol). These children were treated from 1950 to 1973. The peak presentation was in the 2nd and 3rd year of life, with a secondary peak in the 10th year. Anatomical (39%), metabolic (8.5%) or primary infective abnormalities (29%) were demonstrable, but 22% had to be left in an unsatisfactory \"idiopathic classification''. The overall recurrence rate of 7% was reduced to 3.5% when those patients with cystinuria were excluded. The local water supply areas have been studied and a tentative association is suggested between patients and their environment when they live in an area where the water is not only hard but also alkaline (pHgreater than 8).", "contents": "Urinary lithiasis in childhood in the Bristol clinical area. A series of 59 consecutive cases of urinary calculi in childhood is presented, being acquired from one local area (Bristol). These children were treated from 1950 to 1973. The peak presentation was in the 2nd and 3rd year of life, with a secondary peak in the 10th year. Anatomical (39%), metabolic (8.5%) or primary infective abnormalities (29%) were demonstrable, but 22% had to be left in an unsatisfactory \"idiopathic classification''. The overall recurrence rate of 7% was reduced to 3.5% when those patients with cystinuria were excluded. The local water supply areas have been studied and a tentative association is suggested between patients and their environment when they live in an area where the water is not only hard but also alkaline (pHgreater than 8)."}
{"id": "PMID:238285", "title": "Tetrahedral intermediate in a specific alpha-chymotrypsin inhibitor complex detected by laser Raman spectroscopy.", "content": "Laser Raman spectroscopy indicates that inhibition of alpha-chymotrypsin by 2-phenylethaneboronic acid occurs in two steps: (i) the formation of a loosely bound complex, in which the boron remains in a trigonal configuration; and (ii) reaction of the boron with a functional group in the catalytic site of the enzyme, resulting in a reversible, stable tetrahedral adduct.", "contents": "Tetrahedral intermediate in a specific alpha-chymotrypsin inhibitor complex detected by laser Raman spectroscopy. Laser Raman spectroscopy indicates that inhibition of alpha-chymotrypsin by 2-phenylethaneboronic acid occurs in two steps: (i) the formation of a loosely bound complex, in which the boron remains in a trigonal configuration; and (ii) reaction of the boron with a functional group in the catalytic site of the enzyme, resulting in a reversible, stable tetrahedral adduct."}
{"id": "PMID:238286", "title": "Anthopleurine: a sea anemone alarm pheromone.", "content": "The sea anemone Anthopleura elegantissima responds with characteristic contraction to a pheromone released by wounded conspecifics. The alarm pheromone was isolated by ion-exchange chromatography and identified by chemical and spectroscopic methods as the quaternary ammonium ion (3-carboxy-2, 3-dihydroxy-N, N, N-trimethyl)-1-propanaminium. Median effective concentration of the crystalline pheromone is 3.5 X 10-minus 10 mole per liter of seawater.", "contents": "Anthopleurine: a sea anemone alarm pheromone. The sea anemone Anthopleura elegantissima responds with characteristic contraction to a pheromone released by wounded conspecifics. The alarm pheromone was isolated by ion-exchange chromatography and identified by chemical and spectroscopic methods as the quaternary ammonium ion (3-carboxy-2, 3-dihydroxy-N, N, N-trimethyl)-1-propanaminium. Median effective concentration of the crystalline pheromone is 3.5 X 10-minus 10 mole per liter of seawater."}
{"id": "PMID:238291", "title": "A new hyrogen ion telemetry technique for evaluating gastroesophageal reflux.", "content": "A new pH capsule telemetry technique was used to measure the pH fluxes in the upper part of the gastrointestinal tract in normal volunteers, symptomatic patients and in those with hiatal herniorrhaphy during the preoperative and postoperative period. The Darvon-sized pH capsule is swallowed with ease and with minimal discomfort by a fasting patient. The pH of the surrounding media activates an FM radio transmitter within the capsule to emit a continuous radio signal which is converted by a receiver to a linear graph on a strip chart recorder. This pH capsule telemetry test is easy to perform on an ambulatory basis and allows an accurate and reproducible determination of the presence or absence of esophageal reflux in patients with and without a hiatal hernia. Its correlation with symptomatic reflux is higher than that found with a conventional gastrointestinal series examination. The technique allows a much clearer distinction to be made between those patients with real symptomatic esophagitis secondary to actual reflux and those with other esophageal, cardiac or pulmonary symptoms existing withour reflux. This study also reveals a consistently lower fasting gastric pH in patients with signs and symptoms of reflux than in normal individuals without reflux. The technique enabled a more accurate assessment of the efficacy of hiatal hernia repair and revealed a reduced degree of esophageal reflux in those patients who had undergone successful repair with fundic plication.", "contents": "A new hyrogen ion telemetry technique for evaluating gastroesophageal reflux. A new pH capsule telemetry technique was used to measure the pH fluxes in the upper part of the gastrointestinal tract in normal volunteers, symptomatic patients and in those with hiatal herniorrhaphy during the preoperative and postoperative period. The Darvon-sized pH capsule is swallowed with ease and with minimal discomfort by a fasting patient. The pH of the surrounding media activates an FM radio transmitter within the capsule to emit a continuous radio signal which is converted by a receiver to a linear graph on a strip chart recorder. This pH capsule telemetry test is easy to perform on an ambulatory basis and allows an accurate and reproducible determination of the presence or absence of esophageal reflux in patients with and without a hiatal hernia. Its correlation with symptomatic reflux is higher than that found with a conventional gastrointestinal series examination. The technique allows a much clearer distinction to be made between those patients with real symptomatic esophagitis secondary to actual reflux and those with other esophageal, cardiac or pulmonary symptoms existing withour reflux. This study also reveals a consistently lower fasting gastric pH in patients with signs and symptoms of reflux than in normal individuals without reflux. The technique enabled a more accurate assessment of the efficacy of hiatal hernia repair and revealed a reduced degree of esophageal reflux in those patients who had undergone successful repair with fundic plication."}
{"id": "PMID:238292", "title": "Adrenergic mechanisms in the hindlimb circulation of baboons.", "content": "The effects of the adrenergic agonists norepinephrine, epinephrine, isoproterenol, and phenylephrine upon femoral arterial blood flow were measured in baboons before and after alpha (phenoxybenzamine) and beta (propranolol) adrenergic receptor blockade. Flow was measured with an electromagnetic flowmeter. Arterial and venous pressures were recorded simultaneously. Femoral vascular resistance was calculated from these data. Catecholamines were injected intra-arterially (10(-3)--10(0) mug, base, kg.(-1) and intravenously (1.0 mug kg.(-1) in a randomized sequence. All four adrenergic amines were vasodilators at low dose (10(-3) mug kg.(-1), intra-arterially) and this effect was abolished during beta adrenergic receptor blockade. Intra-arterial isoproterenol elicited dose-dependent increases in femoral flow; the other amines were vasoconstrictors at high doses. Alpha adrenergic blockade \"reversed\" the vasoconstrictor effects of these three amines. At the same dose isoproterenol increased flow more through the intra-arterial than the intravenous route. Conversely, norepinephrine and epinephrine were potent femoral vasodilators when injected intravenously. The findings indicate that the classical adrenergic amines are all vasodilators of the subhuman primate hindlimb at low doses due to their interaction with beta receptor sites. The fact that epinephrine and norepinephrine exert a greater increase in flow when given intravenously than when given intra-arterially is presumably secondary to increased arterial pressure, in turn due to the vasoconstrictor effects of these agents on other regional circulations.", "contents": "Adrenergic mechanisms in the hindlimb circulation of baboons. The effects of the adrenergic agonists norepinephrine, epinephrine, isoproterenol, and phenylephrine upon femoral arterial blood flow were measured in baboons before and after alpha (phenoxybenzamine) and beta (propranolol) adrenergic receptor blockade. Flow was measured with an electromagnetic flowmeter. Arterial and venous pressures were recorded simultaneously. Femoral vascular resistance was calculated from these data. Catecholamines were injected intra-arterially (10(-3)--10(0) mug, base, kg.(-1) and intravenously (1.0 mug kg.(-1) in a randomized sequence. All four adrenergic amines were vasodilators at low dose (10(-3) mug kg.(-1), intra-arterially) and this effect was abolished during beta adrenergic receptor blockade. Intra-arterial isoproterenol elicited dose-dependent increases in femoral flow; the other amines were vasoconstrictors at high doses. Alpha adrenergic blockade \"reversed\" the vasoconstrictor effects of these three amines. At the same dose isoproterenol increased flow more through the intra-arterial than the intravenous route. Conversely, norepinephrine and epinephrine were potent femoral vasodilators when injected intravenously. The findings indicate that the classical adrenergic amines are all vasodilators of the subhuman primate hindlimb at low doses due to their interaction with beta receptor sites. The fact that epinephrine and norepinephrine exert a greater increase in flow when given intravenously than when given intra-arterially is presumably secondary to increased arterial pressure, in turn due to the vasoconstrictor effects of these agents on other regional circulations."}
{"id": "PMID:238293", "title": "Effects of pharmacological myocardial depression on coronary artery collateral formation.", "content": "Treatment of angina pectoris falls within two spheres: (1) increasing myocardial blood flow (direct bypass, vasodilators), or (2) reducing oxygen demand (beta blockade, propranolol). If the latter depresses the stimulus for collateralization without improving input, its use in certain forms of coronary disease may require reconsideration. To examine this hypothesis, 25 dogs (four groups) were evaluated by surface mapping, angiographic collateral mapping, and hemodynamic studies including cardiac output, systemic and coronary pressures, coronary flow, and left ventricular end-diastolic pressure, pressure to time (LVdp/dt). Collateralization was induced with ameroid constrictor placement in Groups I, III, and IV. Groups II and III received immediate propranolol treatment (3 to 5 mg. per kilogram per day for 6 weeks); Group IV received delayed treatment (4 weeks after constriction); and Group I received no propranolol (constrictor alone). Collateral formation was depressed significantly in the acutely beta-blockaded dogs (Group III) by surface and angiographic mapping and by hemodynamic evidence of depressed coronary flow and altered coronary retrograde pressures. Alterations in established collaterals (Group IV) were not consistent. These data suggest that pharmacological reduction of myocardial oxygen demand reduces coronary collateralization experimentally, requiring further evaluation of its usage in multivessel coronary disease to the exclusion of direct bypass.", "contents": "Effects of pharmacological myocardial depression on coronary artery collateral formation. Treatment of angina pectoris falls within two spheres: (1) increasing myocardial blood flow (direct bypass, vasodilators), or (2) reducing oxygen demand (beta blockade, propranolol). If the latter depresses the stimulus for collateralization without improving input, its use in certain forms of coronary disease may require reconsideration. To examine this hypothesis, 25 dogs (four groups) were evaluated by surface mapping, angiographic collateral mapping, and hemodynamic studies including cardiac output, systemic and coronary pressures, coronary flow, and left ventricular end-diastolic pressure, pressure to time (LVdp/dt). Collateralization was induced with ameroid constrictor placement in Groups I, III, and IV. Groups II and III received immediate propranolol treatment (3 to 5 mg. per kilogram per day for 6 weeks); Group IV received delayed treatment (4 weeks after constriction); and Group I received no propranolol (constrictor alone). Collateral formation was depressed significantly in the acutely beta-blockaded dogs (Group III) by surface and angiographic mapping and by hemodynamic evidence of depressed coronary flow and altered coronary retrograde pressures. Alterations in established collaterals (Group IV) were not consistent. These data suggest that pharmacological reduction of myocardial oxygen demand reduces coronary collateralization experimentally, requiring further evaluation of its usage in multivessel coronary disease to the exclusion of direct bypass."}
{"id": "PMID:238294", "title": "Effect of aspirin, bile salt, and ethanol on canine gastric mucosal blood flow.", "content": "The effect of aspirin (20 mM.), sodium taurocholate (40 mM.), and ethanol (24 per cent w/v) on gastric mucosal blood flow was studied in an exteriorized, chambered preparation of canine fundic stomach. Gastric mucosal blood flow was measured by gamma-labeled microspheres and plasma aminopyrine clearance. All three test solutions caused a significant increase in microsphere-measured mucosal blood flow. The degree of increase in gastric mucosal blood flow was proportional to the severity of gross mucosal injury, being greatest with bile salt and least with ethanol. Plasma aminopyrine clearance determined only a small fraction of mucosal flow measured by microspheres following injury, particularly in sodium taurocholate and ethanol experiments, where the net hydrogen ion back diffusion was greatest. The results suggest that increased gastric mucosal blood flow may be a secondary defensive response to the damage caused by these irritants and that the plasma aminopyrine clearance is unreliable in quantitating mucosal blood flow changes in the presence of mucosal injury.", "contents": "Effect of aspirin, bile salt, and ethanol on canine gastric mucosal blood flow. The effect of aspirin (20 mM.), sodium taurocholate (40 mM.), and ethanol (24 per cent w/v) on gastric mucosal blood flow was studied in an exteriorized, chambered preparation of canine fundic stomach. Gastric mucosal blood flow was measured by gamma-labeled microspheres and plasma aminopyrine clearance. All three test solutions caused a significant increase in microsphere-measured mucosal blood flow. The degree of increase in gastric mucosal blood flow was proportional to the severity of gross mucosal injury, being greatest with bile salt and least with ethanol. Plasma aminopyrine clearance determined only a small fraction of mucosal flow measured by microspheres following injury, particularly in sodium taurocholate and ethanol experiments, where the net hydrogen ion back diffusion was greatest. The results suggest that increased gastric mucosal blood flow may be a secondary defensive response to the damage caused by these irritants and that the plasma aminopyrine clearance is unreliable in quantitating mucosal blood flow changes in the presence of mucosal injury."}
{"id": "PMID:238295", "title": "The role of acid and ischemia in production of stress ulcers during canine hemorrhagic shock.", "content": "Hemorrhage to a mean arterial pressure of 41 mm. Hg in ten dogs decreased Heidenhain pouch blood flow to 6 ml. per minute and aminopyrine clearance to 0.93 ml. per minute. Pouch oxygen consumption fell from 1.47 to 0.74 ml./min.-100 Gm. and total body oxygen consumption remained unchanged. Net ion fluxes during shock and reinfusion did not change significantly from control values of minus 89.8 muGq./30 min.-100 cm.-2 for H-+ and 88.6 muEq./30 min.-100 cm-2 for Na-+. However, PD decreased from 54 to 24 mv. in parallel with a fall in net Cl-minus flux from 56.8 to minus 11.7 muEq./30 min.-100 cm-2. Nine of ten pouches subjected to shock and instilled acid test solution (ATS) developed superficial mucosal erosions. No ulcerations were found in either seven control dogs (anesthesia + ATS) or in three dogs subjected to shock without ATS. Acid appears to be of prime importance in the production of stress ulcers during or following ischemia, even though there is no increase in mucosal ionic permeability.", "contents": "The role of acid and ischemia in production of stress ulcers during canine hemorrhagic shock. Hemorrhage to a mean arterial pressure of 41 mm. Hg in ten dogs decreased Heidenhain pouch blood flow to 6 ml. per minute and aminopyrine clearance to 0.93 ml. per minute. Pouch oxygen consumption fell from 1.47 to 0.74 ml./min.-100 Gm. and total body oxygen consumption remained unchanged. Net ion fluxes during shock and reinfusion did not change significantly from control values of minus 89.8 muGq./30 min.-100 cm.-2 for H-+ and 88.6 muEq./30 min.-100 cm-2 for Na-+. However, PD decreased from 54 to 24 mv. in parallel with a fall in net Cl-minus flux from 56.8 to minus 11.7 muEq./30 min.-100 cm-2. Nine of ten pouches subjected to shock and instilled acid test solution (ATS) developed superficial mucosal erosions. No ulcerations were found in either seven control dogs (anesthesia + ATS) or in three dogs subjected to shock without ATS. Acid appears to be of prime importance in the production of stress ulcers during or following ischemia, even though there is no increase in mucosal ionic permeability."}
{"id": "PMID:238296", "title": "The intestinal phase of gastric secretion: a pharmacological profile of entero-oxyntin.", "content": "In dogs with denervated fundic pouches, antrectomy, and gastrojejunostomy, feeding a meal of cooked liver and 5 percent bone dust stimualted acid secretion from the fundic pouches without increasing serum gastrin concentrations. Simultaneous administration of pentagastrin, histamine, octapeptide of cholecystokinin, or bethanecol produced potentiation of acid secretion, suggesting that the mediator of the intestinal phase is different from these secretagogues. Secretin and glucagon failed to inhibit the intestinal stimulus but both atropine and metiamide were potent inhibitors. We conclude that entero-oxyntin, the hormone responsible for the intestinal phase of gastric secretin, has a unique pattern of effects for acid secretion.", "contents": "The intestinal phase of gastric secretion: a pharmacological profile of entero-oxyntin. In dogs with denervated fundic pouches, antrectomy, and gastrojejunostomy, feeding a meal of cooked liver and 5 percent bone dust stimualted acid secretion from the fundic pouches without increasing serum gastrin concentrations. Simultaneous administration of pentagastrin, histamine, octapeptide of cholecystokinin, or bethanecol produced potentiation of acid secretion, suggesting that the mediator of the intestinal phase is different from these secretagogues. Secretin and glucagon failed to inhibit the intestinal stimulus but both atropine and metiamide were potent inhibitors. We conclude that entero-oxyntin, the hormone responsible for the intestinal phase of gastric secretin, has a unique pattern of effects for acid secretion."}
{"id": "PMID:238304", "title": "[Use of neuroleptic agents in modern pig-farming (author's transl)].", "content": "in pig-farming, the use of neuroleptic agents in conditions causing stress has increased. In the meaty type pig, this stress gives rise to specific symptoms such as acidosis, hyperthermia and muscle rigidity. This will result in death before or an abnormal meat quality (PSE-meat) after slaughter. The symptoms may also be produced in these pigs by having them inhale halothane (Fluothane), the symptoms being rapidly reversible. The inhibitory effect of various neuroleptic agents of the group of butyrophenone and phenothiazine derivatives on the appearance and course of the above symptoms is discussed. The extent to which the quality of the meat and mortality during transport is affected following administration of these agents to slaughter pigs as well as the degree to which hypersensitivity reactions to halothane are reduced in young pigs serve as models. Finally, public health and ethical aspects relating to the use of neuroleptic agents in farm animals are examined more closely.", "contents": "[Use of neuroleptic agents in modern pig-farming (author's transl)]. in pig-farming, the use of neuroleptic agents in conditions causing stress has increased. In the meaty type pig, this stress gives rise to specific symptoms such as acidosis, hyperthermia and muscle rigidity. This will result in death before or an abnormal meat quality (PSE-meat) after slaughter. The symptoms may also be produced in these pigs by having them inhale halothane (Fluothane), the symptoms being rapidly reversible. The inhibitory effect of various neuroleptic agents of the group of butyrophenone and phenothiazine derivatives on the appearance and course of the above symptoms is discussed. The extent to which the quality of the meat and mortality during transport is affected following administration of these agents to slaughter pigs as well as the degree to which hypersensitivity reactions to halothane are reduced in young pigs serve as models. Finally, public health and ethical aspects relating to the use of neuroleptic agents in farm animals are examined more closely."}
{"id": "PMID:238305", "title": "[Fluid therapy (author's transl)].", "content": "An introductory part concerned with the distribution of fluid and electrolytes over the various compartments of the body and the acid-base regulation is followed by a discussion of the fluid balance and pathological losses of fluid and electrolytes. An assessment of patients showing dehydration is based on the histories, clinical examination and laboratory studies, in order to gain an impression of the state of hydration, electrolyte deficiencies, acid-base equilibrium, caloric requirements and renal function. The guidelines for fluid therapy include the scheme of this form of treatment, some comments on the available fluids and the techniques in large and small animals.", "contents": "[Fluid therapy (author's transl)]. An introductory part concerned with the distribution of fluid and electrolytes over the various compartments of the body and the acid-base regulation is followed by a discussion of the fluid balance and pathological losses of fluid and electrolytes. An assessment of patients showing dehydration is based on the histories, clinical examination and laboratory studies, in order to gain an impression of the state of hydration, electrolyte deficiencies, acid-base equilibrium, caloric requirements and renal function. The guidelines for fluid therapy include the scheme of this form of treatment, some comments on the available fluids and the techniques in large and small animals."}
{"id": "PMID:238306", "title": "The ciliary-cone sensory cell of anemones and cerianthids.", "content": "An ultrastructural study of the tentacles of Stomphia and of Ceriantheopsis has revealed that the so-called 'ciliary-cone sensory cell' consists of a cluster of five to seven apparent receptors rather than just one cell as reported previously. At the center of a cluster is a single cell, whose dendrite bears one cilium surrounded by about ten large stereocilia. Surrounding this cell are a number of peripheral cells whose dendrites bear large numbers of small stereocilia and, in Ceriantheopsis, one cilium. The sensory apparatuses of all cells in a cluster unite to form a single unit projecting above the tissue surface: the ciliary cone. Their possible physiological role is discussed in relation to new behavioural observations.", "contents": "The ciliary-cone sensory cell of anemones and cerianthids. An ultrastructural study of the tentacles of Stomphia and of Ceriantheopsis has revealed that the so-called 'ciliary-cone sensory cell' consists of a cluster of five to seven apparent receptors rather than just one cell as reported previously. At the center of a cluster is a single cell, whose dendrite bears one cilium surrounded by about ten large stereocilia. Surrounding this cell are a number of peripheral cells whose dendrites bear large numbers of small stereocilia and, in Ceriantheopsis, one cilium. The sensory apparatuses of all cells in a cluster unite to form a single unit projecting above the tissue surface: the ciliary cone. Their possible physiological role is discussed in relation to new behavioural observations."}
{"id": "PMID:238314", "title": "Arbovirus infections in Sarawak, October 1968-February 1970: GETAH virus isolations from mosquitoes.", "content": "14 strains of Getah virus were isolated from a variety of mosquito species collected in Sarawak between October 1968 and February 1970. Ten strains were isolated from C. tritaeniorhynchus 7 of them at K. Tijirak. Single strains were isolated from C. gelidus, C. pseudovishnui, M. bonneae/dives and Aanopheles species. 6 of the isolates were obtained in October 1968 when Japanese encephalitis, Tembusu and Sindbis viruses were also very active. The available evidence suggest that Getah virus in Sarawak is maintained in a cycle similar to that of Japanese encephalitis virus and involves C. tritaeniorhynchus, C. gelidus and domestic pigs.", "contents": "Arbovirus infections in Sarawak, October 1968-February 1970: GETAH virus isolations from mosquitoes. 14 strains of Getah virus were isolated from a variety of mosquito species collected in Sarawak between October 1968 and February 1970. Ten strains were isolated from C. tritaeniorhynchus 7 of them at K. Tijirak. Single strains were isolated from C. gelidus, C. pseudovishnui, M. bonneae/dives and Aanopheles species. 6 of the isolates were obtained in October 1968 when Japanese encephalitis, Tembusu and Sindbis viruses were also very active. The available evidence suggest that Getah virus in Sarawak is maintained in a cycle similar to that of Japanese encephalitis virus and involves C. tritaeniorhynchus, C. gelidus and domestic pigs."}
{"id": "PMID:238316", "title": "A purine nucleoside hydrolase from Trypanosoma gambiense, purification and properties.", "content": "A purine nucleoside hydrolase from Trypanosoma gambiense was purified 160-fold. Preferred substrates of the reaction were adenosine, inosine and guanosine with a maximum of activity at pH 5.4. Competitive inhibitors of the adenosine hydrolysis were dimethylallyl adenosine, 6-methylmercaptopurine riboside, tubercidin, formycin B, 6-mercaptopurine riboside and deoxyadenosine. A metabolic scheme of adenosine nomophosphate salvage synthesis is discussed.", "contents": "A purine nucleoside hydrolase from Trypanosoma gambiense, purification and properties. A purine nucleoside hydrolase from Trypanosoma gambiense was purified 160-fold. Preferred substrates of the reaction were adenosine, inosine and guanosine with a maximum of activity at pH 5.4. Competitive inhibitors of the adenosine hydrolysis were dimethylallyl adenosine, 6-methylmercaptopurine riboside, tubercidin, formycin B, 6-mercaptopurine riboside and deoxyadenosine. A metabolic scheme of adenosine nomophosphate salvage synthesis is discussed."}
{"id": "PMID:238317", "title": "The relationship between length of incubation, bacterial growth and tuberculin yield of a strain of Mycobacterium tuberculosis.", "content": "The relationship was studied between length of incubation in a liquid synthetic medium, amount of bacterial growth, pH of the culture filtrate and tuberculin yield of a single strain, DT, of Mycobacterium tuberculosis. No sinple relationship was found between the total crop of bacteria and the tuberculoprotein content of the culture filtrate. On the other hand, protein release and the pH of the culture filtrate were closely related. In each of two trials the bacterial crop increased rapidly during the early period of incubation, although maximum growth was not reached until 9 and 13 weeks respectively. The pH of the culture filtrate reached its maximum at a value of more than 9-0 after 5 weeks incubation and then fell until the 10th week; a second rise occurred until the 13th week when the pH dropped again and levelled off slightly on the alkaline side of neutrality. The rate of increase in tuberculin yield was most rapid during the first 7 weeks of incubation. After this, the rate of increase slowed down but the yield was still rising after 18 weeks. It is concluded that for the large-scale production of mammalian tuberculin by the method used in these trials, it is profitable to incubate production cultures for 14 weeks or longer.", "contents": "The relationship between length of incubation, bacterial growth and tuberculin yield of a strain of Mycobacterium tuberculosis. The relationship was studied between length of incubation in a liquid synthetic medium, amount of bacterial growth, pH of the culture filtrate and tuberculin yield of a single strain, DT, of Mycobacterium tuberculosis. No sinple relationship was found between the total crop of bacteria and the tuberculoprotein content of the culture filtrate. On the other hand, protein release and the pH of the culture filtrate were closely related. In each of two trials the bacterial crop increased rapidly during the early period of incubation, although maximum growth was not reached until 9 and 13 weeks respectively. The pH of the culture filtrate reached its maximum at a value of more than 9-0 after 5 weeks incubation and then fell until the 10th week; a second rise occurred until the 13th week when the pH dropped again and levelled off slightly on the alkaline side of neutrality. The rate of increase in tuberculin yield was most rapid during the first 7 weeks of incubation. After this, the rate of increase slowed down but the yield was still rising after 18 weeks. It is concluded that for the large-scale production of mammalian tuberculin by the method used in these trials, it is profitable to incubate production cultures for 14 weeks or longer."}
{"id": "PMID:238320", "title": "Foreign bodies and urinary stones.", "content": "Experimental and clinical aspects of calculogenesis about foreign bodies are reviewed. Factors such as infections, urine dilution, urinary pH, and suture materials are discussed from an investigative point of view. The various kinds of clinical foreign body stones reported are categorized according to the manner of introduction into the urinary tract and anatomic locations.", "contents": "Foreign bodies and urinary stones. Experimental and clinical aspects of calculogenesis about foreign bodies are reviewed. Factors such as infections, urine dilution, urinary pH, and suture materials are discussed from an investigative point of view. The various kinds of clinical foreign body stones reported are categorized according to the manner of introduction into the urinary tract and anatomic locations."}
{"id": "PMID:238322", "title": "Imipramine hydrochloride: pharmacodynamic effects on lower urinary tract of female dogs.", "content": "Our study of the pharmacodynamics of imipramine hydrochloride of the female canine lower urinary tract indicates the primary mode of action to be the stimulation of alpha adrenergic neuroreceptors in the bladder neck and urethra.  This stimulation results in increased resting urethral pressure, adequate sphincter closure, possibly an increase in the bladder capacity and efficient urinary control.  Imipramine had no anticholinergic effect on the bladder and the urethra.  It also appears unlikely that in enuretic patients imipramine acts by central augmentation of the adrenergic system.  No change was noticed in the intravesical or arterial pressures.", "contents": "Imipramine hydrochloride: pharmacodynamic effects on lower urinary tract of female dogs. Our study of the pharmacodynamics of imipramine hydrochloride of the female canine lower urinary tract indicates the primary mode of action to be the stimulation of alpha adrenergic neuroreceptors in the bladder neck and urethra.  This stimulation results in increased resting urethral pressure, adequate sphincter closure, possibly an increase in the bladder capacity and efficient urinary control.  Imipramine had no anticholinergic effect on the bladder and the urethra.  It also appears unlikely that in enuretic patients imipramine acts by central augmentation of the adrenergic system.  No change was noticed in the intravesical or arterial pressures."}
{"id": "PMID:238323", "title": "Use of methenamine hippurate in male infertility.", "content": "In sperm-freezing for infertility patients with low sperm counts, we found that semen containing high numbers of white blood cells, greater than 15 to 20 per high-power field, was both poor in quality and difficult to freeze. In examining these patients carefully, we found that many had smoldering prostatitis and some an overt history of prostatitis. We treated them with methenamine hippurate using various methods and found that by decreasing the white blood cell count in their semen, we could frequently improve the semen quality, particularly sperm motility, also achieve pregnancies in some cases.", "contents": "Use of methenamine hippurate in male infertility. In sperm-freezing for infertility patients with low sperm counts, we found that semen containing high numbers of white blood cells, greater than 15 to 20 per high-power field, was both poor in quality and difficult to freeze. In examining these patients carefully, we found that many had smoldering prostatitis and some an overt history of prostatitis. We treated them with methenamine hippurate using various methods and found that by decreasing the white blood cell count in their semen, we could frequently improve the semen quality, particularly sperm motility, also achieve pregnancies in some cases."}
{"id": "PMID:238324", "title": "Microsurgery in clinical urology.", "content": "Microsurgery is not a new tool to the urologist. Transurethral resection is probably the most challenging type of microsurgery, and we do it daily. The manipulations of microvascular dissections and anastomoses may be more intricate, but the basic concept of performing delicate procedures while looking down a tube is \"old hat\" to us. The new techniques discussed here may extend the range of operative solutions to difficult clinical problems in urology perhaps as transurethral resection did in the thirties and forties.", "contents": "Microsurgery in clinical urology. Microsurgery is not a new tool to the urologist. Transurethral resection is probably the most challenging type of microsurgery, and we do it daily. The manipulations of microvascular dissections and anastomoses may be more intricate, but the basic concept of performing delicate procedures while looking down a tube is \"old hat\" to us. The new techniques discussed here may extend the range of operative solutions to difficult clinical problems in urology perhaps as transurethral resection did in the thirties and forties."}
{"id": "PMID:238325", "title": "Urologic problems associated with imperforate anus.", "content": "A total of 120 children with both high, intermediate, and low types of imperforate anus were evaluated urologically. Genitourinary anomalies were associated with all types of imperforate anus but were found more often in children with high rectal deformities. Because the over-all incidence of genitourinary anomalies was high, early and complete urologic evaluation is necessary to achieve the best functional result.", "contents": "Urologic problems associated with imperforate anus. A total of 120 children with both high, intermediate, and low types of imperforate anus were evaluated urologically. Genitourinary anomalies were associated with all types of imperforate anus but were found more often in children with high rectal deformities. Because the over-all incidence of genitourinary anomalies was high, early and complete urologic evaluation is necessary to achieve the best functional result."}
{"id": "PMID:238328", "title": "Five-day partial bypass using a membrane oxygenator without systemic heparinzation.", "content": "These studies indicate that a heparin bound membrane oxygenator can be used in venovenous bypass circuit in dogs for a period of 5 days without systemic heparinization. The plasma SGOT, plasma hemoglobin, and MLW of the animals increased after initiation of bypass but returned to control levels. Oxygen transfer did not deteriorate in the membrane oxygenator, eliminating the necessity of membrane exchange during the 5-day bypass.", "contents": "Five-day partial bypass using a membrane oxygenator without systemic heparinzation. These studies indicate that a heparin bound membrane oxygenator can be used in venovenous bypass circuit in dogs for a period of 5 days without systemic heparinization. The plasma SGOT, plasma hemoglobin, and MLW of the animals increased after initiation of bypass but returned to control levels. Oxygen transfer did not deteriorate in the membrane oxygenator, eliminating the necessity of membrane exchange during the 5-day bypass."}
{"id": "PMID:238330", "title": "[Annual dynamics of acidobasic indices in the sheep blood].", "content": "Altogether 218 sheep were followed for a year and the values of their acidobasic indices were examined, the follow-up comprises all seasons of the year, gravidity period, time of nursing and milk production. The actual pH value in the sheep blood varied from 7.30 to 7.48, with 7.40 average. The average value of partial CO2 pressure amounted to 37.26 torr the individual values varying between 30.0 and 47.5 torr. Baz excess varies from +5.0 to -6.3 mval/1 blood with year average of 1.11 mval/1 blood. Buffer baz was 43.0 mval/1 on the average, with variations from 34.2 to 48.9 mval/1 blood. Standard bicarbonate showed a relatively broad range of values from 19.0 to 28.0 mval/1 plasma, with 22.85 mval/1 average. Actual bicarbonate manifested similar variation dynamics as SB. Annual average was 22.92 mval/1 plasma, with variations from 19.0 to 28.2 mval/1. Total plasmatic CO2 had balanced average monthly values, with year average of 23.84 mval/1. Generally it can be concluded that after the sheep being out to grass the acidobasic blood indices became regulated.", "contents": "[Annual dynamics of acidobasic indices in the sheep blood]. Altogether 218 sheep were followed for a year and the values of their acidobasic indices were examined, the follow-up comprises all seasons of the year, gravidity period, time of nursing and milk production. The actual pH value in the sheep blood varied from 7.30 to 7.48, with 7.40 average. The average value of partial CO2 pressure amounted to 37.26 torr the individual values varying between 30.0 and 47.5 torr. Baz excess varies from +5.0 to -6.3 mval/1 blood with year average of 1.11 mval/1 blood. Buffer baz was 43.0 mval/1 on the average, with variations from 34.2 to 48.9 mval/1 blood. Standard bicarbonate showed a relatively broad range of values from 19.0 to 28.0 mval/1 plasma, with 22.85 mval/1 average. Actual bicarbonate manifested similar variation dynamics as SB. Annual average was 22.92 mval/1 plasma, with variations from 19.0 to 28.2 mval/1. Total plasmatic CO2 had balanced average monthly values, with year average of 23.84 mval/1. Generally it can be concluded that after the sheep being out to grass the acidobasic blood indices became regulated."}
{"id": "PMID:238331", "title": "[Values of acido-basic balance in the blood of the beagle breed dog in comparison with the German shepherd dog].", "content": "The values of acidobasic balance were examined in 101 dogs of the Beagle breed and in 20 German Sheep-Dogs. The Beagle dogs were divided into five age groups. A difference was found between the values obtained in the group of the youngest dogs and those in older age groups. In comparison with Beagle dogs, the values were higher in German Sheep-Dogs (pH, base excess). A figure is attached representing the deviations of the values of acidobasic balance of blood in the two breeds.", "contents": "[Values of acido-basic balance in the blood of the beagle breed dog in comparison with the German shepherd dog]. The values of acidobasic balance were examined in 101 dogs of the Beagle breed and in 20 German Sheep-Dogs. The Beagle dogs were divided into five age groups. A difference was found between the values obtained in the group of the youngest dogs and those in older age groups. In comparison with Beagle dogs, the values were higher in German Sheep-Dogs (pH, base excess). A figure is attached representing the deviations of the values of acidobasic balance of blood in the two breeds."}
{"id": "PMID:238332", "title": "Veterinary aspects of salmonid fish farming: husbandry.", "content": "A knowledge of environmental requirements is important in order to obtain good growth and health when farming salmonid fish. Biological requirements are discussed, including water quality parameters and nutritional aspects. The main techniques used for farming salmonids are described together with the annual cycle of operations undertaken on a commercial trout farm.", "contents": "Veterinary aspects of salmonid fish farming: husbandry. A knowledge of environmental requirements is important in order to obtain good growth and health when farming salmonid fish. Biological requirements are discussed, including water quality parameters and nutritional aspects. The main techniques used for farming salmonids are described together with the annual cycle of operations undertaken on a commercial trout farm."}
{"id": "PMID:238333", "title": "Studies on the modification of the cellular response to injury. II. Electron microscopic studies on the protective effect of acidosis on anoxic injury of Ehrlich ascites tumor cells.", "content": "Extracellular acidosis (ph 5.9 to 6.5) was found to be significantly retard the subcellular response of Ehrlich ascites tumor cells (EATC) to anoxic injury. The cells initially showed a reversible stage of cell injury with diffuse mitrochondrial condensation and swelling of endoplasmic reticulum (ER) at pH 7.9 by 1 h, while by 3 h at this pH all cells showed high amplitude and intramatrical flocculent densities of mitochondria, and fragmentation of membrane systems. At pH 7.4 cells were normal at 15 min., the mitochondria were condensed as above by 1 h, some cells still showed condensed mitochondria and dilated ER while others showed high amplitude swelling of mitochondria by 3 h and all cells showed irreversible changes by 4 h. At pH 5.9 to pH 6.5 mitochondria remained condensed until 3 h and only by 6 h did some cells show high amplitude swelling, whereas most cells showed persistent mitrochondrial condensation. Not until 8 h did all cells show high amplitude swelling of mitochondria. Furthermore, ultrastructural differences in the pattern of necrosis were seen at the lower pH values consisting of greater density of the cell sap, irregularly dispersed flocculent densities in apposition to fragmented cytoplasmic membranes and in mitochondria, and more prominent persistent clumping of nuclear chromatin.", "contents": "Studies on the modification of the cellular response to injury. II. Electron microscopic studies on the protective effect of acidosis on anoxic injury of Ehrlich ascites tumor cells. Extracellular acidosis (ph 5.9 to 6.5) was found to be significantly retard the subcellular response of Ehrlich ascites tumor cells (EATC) to anoxic injury. The cells initially showed a reversible stage of cell injury with diffuse mitrochondrial condensation and swelling of endoplasmic reticulum (ER) at pH 7.9 by 1 h, while by 3 h at this pH all cells showed high amplitude and intramatrical flocculent densities of mitochondria, and fragmentation of membrane systems. At pH 7.4 cells were normal at 15 min., the mitochondria were condensed as above by 1 h, some cells still showed condensed mitochondria and dilated ER while others showed high amplitude swelling of mitochondria by 3 h and all cells showed irreversible changes by 4 h. At pH 5.9 to pH 6.5 mitochondria remained condensed until 3 h and only by 6 h did some cells show high amplitude swelling, whereas most cells showed persistent mitrochondrial condensation. Not until 8 h did all cells show high amplitude swelling of mitochondria. Furthermore, ultrastructural differences in the pattern of necrosis were seen at the lower pH values consisting of greater density of the cell sap, irregularly dispersed flocculent densities in apposition to fragmented cytoplasmic membranes and in mitochondria, and more prominent persistent clumping of nuclear chromatin."}
{"id": "PMID:238334", "title": "Studies on the modification of the cellular response to injury. III. Electron microscopic studies on the protective effect of acidosis on p-chloromercuribenzene sulfonic acid-(PCMBS) induced injury of Ehrlich ascites tumor cells.", "content": "Extracellular acidosis (pH 6.5) was found to significantly retard the response of Ehrlich ascites tumor cells (EATC) to direct plasma membrane injury with the non-penetrating organic mercurial compound, p-chloromercuribenzene sulfonic acid (PCMBS). Treatment of cells with 1 mM PCMBS resulted in loss of viability of all cells by 45 minutes at pH 7.4, and by 90 minutes at pH 6.5. Pregression of cellular changes through the various stages of cell injury at the ultrastructural level was correspondingly slower at pH 6.5. The results support the concept that stage 3 of cell injury, associated with condensed mitochondria, dilated ER and swollen cell sap is compatible with cell survival, while stage 5 with high amplitude swelling of mitochondria, fragmentation of membrane systems, and beginning of karyolysis is characteristic of irreversible injury. All cells entered stage 3 at 7.5 minutes at pH 7.4, while essentially all cells entered stage 5 by 45 minutes. At pH 6.5, stage 3 was maintained for 45 minutes and 100% of the cells entered stage 5 by 90 minutes. Although the mechanism of the protection against PCMBS-induced injury is not known, the present electron microscopical results are compatible with the hypothesis that the extracellular acidosis acts to partially stabilize plasma membrane, perhaps by interaction with sulfhydryl (SH) groups.", "contents": "Studies on the modification of the cellular response to injury. III. Electron microscopic studies on the protective effect of acidosis on p-chloromercuribenzene sulfonic acid-(PCMBS) induced injury of Ehrlich ascites tumor cells. Extracellular acidosis (pH 6.5) was found to significantly retard the response of Ehrlich ascites tumor cells (EATC) to direct plasma membrane injury with the non-penetrating organic mercurial compound, p-chloromercuribenzene sulfonic acid (PCMBS). Treatment of cells with 1 mM PCMBS resulted in loss of viability of all cells by 45 minutes at pH 7.4, and by 90 minutes at pH 6.5. Pregression of cellular changes through the various stages of cell injury at the ultrastructural level was correspondingly slower at pH 6.5. The results support the concept that stage 3 of cell injury, associated with condensed mitochondria, dilated ER and swollen cell sap is compatible with cell survival, while stage 5 with high amplitude swelling of mitochondria, fragmentation of membrane systems, and beginning of karyolysis is characteristic of irreversible injury. All cells entered stage 3 at 7.5 minutes at pH 7.4, while essentially all cells entered stage 5 by 45 minutes. At pH 6.5, stage 3 was maintained for 45 minutes and 100% of the cells entered stage 5 by 90 minutes. Although the mechanism of the protection against PCMBS-induced injury is not known, the present electron microscopical results are compatible with the hypothesis that the extracellular acidosis acts to partially stabilize plasma membrane, perhaps by interaction with sulfhydryl (SH) groups."}
{"id": "PMID:238335", "title": "Experimental porphyria induced by 3-(2,4,6-trimethylphenyl)-thioethyl)-4 methylsydnone.", "content": "Administration of 3-[2-(2,4,6-trimethylphenyl)-thioethyl]-4-methylsydnone (TTMS) induces hepatic porphyria in rats, mice and dogs. The protoporphyrin pigment in livers of rats and mice is found mainly in bile ducts and leads to bile duct proliferation and portal inflammation. Dog livers contain protoporphyrin predominantly in bile canaliculi. The birefringence of the pigment appears to be associated with bilamellar components within the pigment. The markedly depressed catalase activity in livers of rats does not increase after clofibrate administration. The catalase activity of mouse liver is depressed slightly and responds to clofibrate treatment.", "contents": "Experimental porphyria induced by 3-(2,4,6-trimethylphenyl)-thioethyl)-4 methylsydnone. Administration of 3-[2-(2,4,6-trimethylphenyl)-thioethyl]-4-methylsydnone (TTMS) induces hepatic porphyria in rats, mice and dogs. The protoporphyrin pigment in livers of rats and mice is found mainly in bile ducts and leads to bile duct proliferation and portal inflammation. Dog livers contain protoporphyrin predominantly in bile canaliculi. The birefringence of the pigment appears to be associated with bilamellar components within the pigment. The markedly depressed catalase activity in livers of rats does not increase after clofibrate administration. The catalase activity of mouse liver is depressed slightly and responds to clofibrate treatment."}
{"id": "PMID:238337", "title": "Anticomplementary activity of human immunoglobulin G. I. Mechanism of the artifactual increase in anticomplementary activity of IgG during the assay.", "content": "The anticomplementary activity of IgG can be increased up to 20-fold by pipetting during the preparation of serial dilutions for the assay of this activity. Albumin, if added to the IgG solution before the serial dilutions, completely prevents this artifactual increase in activity. Polyethylene glycol, polyvinyl pyrrolidone, methyl cellulose, gelatin and octanol are also effective stabilizers of IgG. Repeated pipetting of IgG solutions caused marked linear increase in their anticomplementary activity. The formed anticomplementary activity was due to small amounts of highly aggregated protein. The amount of activity formed depended on at least four factors: [1] the number of pipetting steps; [2] the IgG concentration; [3] the level of albumin or other stabilizers, and [4] the pH, which influences the stabilization by albumin. The anticomplementary activity of IgG is increased up to 100-fold by exposure to gas-liquid, liquid-liquid and hydrophobic solid-liquid interfaces. Albumin and polyethylene glycol prevent the activity increase during these treatments. The tendency of IgG to aggregate at interfaces and the ability of albumin and other substances to prevent the aggregation paralleled their rate of adsorption to the air-water interface. Solutions of dansyl chloride in decane emulsified in aqueous solutions of IgG and albumin specifically label the proteins at the liquid-liquid interfaces. The mechanism of stabilization can be explained by preferential adsorption of surface-active proteins and polymers.", "contents": "Anticomplementary activity of human immunoglobulin G. I. Mechanism of the artifactual increase in anticomplementary activity of IgG during the assay. The anticomplementary activity of IgG can be increased up to 20-fold by pipetting during the preparation of serial dilutions for the assay of this activity. Albumin, if added to the IgG solution before the serial dilutions, completely prevents this artifactual increase in activity. Polyethylene glycol, polyvinyl pyrrolidone, methyl cellulose, gelatin and octanol are also effective stabilizers of IgG. Repeated pipetting of IgG solutions caused marked linear increase in their anticomplementary activity. The formed anticomplementary activity was due to small amounts of highly aggregated protein. The amount of activity formed depended on at least four factors: [1] the number of pipetting steps; [2] the IgG concentration; [3] the level of albumin or other stabilizers, and [4] the pH, which influences the stabilization by albumin. The anticomplementary activity of IgG is increased up to 100-fold by exposure to gas-liquid, liquid-liquid and hydrophobic solid-liquid interfaces. Albumin and polyethylene glycol prevent the activity increase during these treatments. The tendency of IgG to aggregate at interfaces and the ability of albumin and other substances to prevent the aggregation paralleled their rate of adsorption to the air-water interface. Solutions of dansyl chloride in decane emulsified in aqueous solutions of IgG and albumin specifically label the proteins at the liquid-liquid interfaces. The mechanism of stabilization can be explained by preferential adsorption of surface-active proteins and polymers."}
{"id": "PMID:238338", "title": "Studies on citrate-phosphate-dextrose (CPD) blood supplemented with adenine.", "content": "The effect of varying adenine concentrations in citrate-phosphate-dextrose (CPD) blood was studied in an attempt to optimize the storage conditions for human erythrocytes with regard to posttransfusion viability and oxygen release function. The maintenance of diphosphoglycerate (DPG) was impaired by adenine supplementation; this effect was closely related to the adenine concentration. A 0.25 mM adenine concentration in CPD blood improved the adenosine triphosphate (ATP) levels and the posttransfusion viability markedly, without appreciably impairing the DPG maintenance. The results suggest that CPD solution supplemented with adenine to give a 0.25 mM concentration in the blood is a better preservative for human erythrocytes than the commonly used acid-citrate-dextrose (ACD), CPD, and ACD-adenine solutions with regard to posttransfusion viability and oxygen release function. Adenine addition to this low concentration is not expected to cause renal damage even after massive transfusion.", "contents": "Studies on citrate-phosphate-dextrose (CPD) blood supplemented with adenine. The effect of varying adenine concentrations in citrate-phosphate-dextrose (CPD) blood was studied in an attempt to optimize the storage conditions for human erythrocytes with regard to posttransfusion viability and oxygen release function. The maintenance of diphosphoglycerate (DPG) was impaired by adenine supplementation; this effect was closely related to the adenine concentration. A 0.25 mM adenine concentration in CPD blood improved the adenosine triphosphate (ATP) levels and the posttransfusion viability markedly, without appreciably impairing the DPG maintenance. The results suggest that CPD solution supplemented with adenine to give a 0.25 mM concentration in the blood is a better preservative for human erythrocytes than the commonly used acid-citrate-dextrose (ACD), CPD, and ACD-adenine solutions with regard to posttransfusion viability and oxygen release function. Adenine addition to this low concentration is not expected to cause renal damage even after massive transfusion."}
{"id": "PMID:238339", "title": "Australia antigen 'ad' and 'ay' subtypes. Purification and partial characterization.", "content": "The two commonly-found Australia antigen subtypes have been purified by simple inexpensive, reproducible, physico-chemical methods involving ammonium sulfate precipitation, peptic digestion, calcium phosphate gel fractionation and molecular sieving on Sepharose 4B. The overall recovery of the two subtypes varied between 50 and 60% of the total antigen content on the starting serum. The purified antigens were found homogeneous by discontinuous gel electrophoresis, analytical ultracentrifugation, and isopycnic banding ultracentrifugation. No contaminating serum proteins could be detected by immunoelectrophoresis. The two purified antigen subtypes have similar Stokes radii and buoyant densities. The sedimentation coefficients for the 'ad' and 'ay' subtypes were found to be 33.0 and 40.1 times 10- minus 13 sec, respectively.", "contents": "Australia antigen 'ad' and 'ay' subtypes. Purification and partial characterization. The two commonly-found Australia antigen subtypes have been purified by simple inexpensive, reproducible, physico-chemical methods involving ammonium sulfate precipitation, peptic digestion, calcium phosphate gel fractionation and molecular sieving on Sepharose 4B. The overall recovery of the two subtypes varied between 50 and 60% of the total antigen content on the starting serum. The purified antigens were found homogeneous by discontinuous gel electrophoresis, analytical ultracentrifugation, and isopycnic banding ultracentrifugation. No contaminating serum proteins could be detected by immunoelectrophoresis. The two purified antigen subtypes have similar Stokes radii and buoyant densities. The sedimentation coefficients for the 'ad' and 'ay' subtypes were found to be 33.0 and 40.1 times 10- minus 13 sec, respectively."}
{"id": "PMID:238340", "title": "The non-Mendelian inheritance of Lewis-c blood group substance, as demonstrated in the case of a Bombay, Le(a-b-c-) saliva.", "content": "A Bombay, Le(a-b-) saliva was shown to lack Pneumococcus type XIV activity, an unusual situation, since this sample should be rich in this precursor to the ABO blood group substances. However, the sample was found to contain a new serological specificity, Le-c. It is argued that simple Mendelian inheritance does not occur with Le-c and single gene control cannot be demonstrated. Failure to repress a fetal gene at birth, as implicated by the similarity in structure between Le-c and carcinoembryonic antigen [SIMMONS and PERLMANN], has been excluded as the mechanism of inheritance of this blood group substance, due to the inability to detect carcinoembryonic antigen in the test saliva.", "contents": "The non-Mendelian inheritance of Lewis-c blood group substance, as demonstrated in the case of a Bombay, Le(a-b-c-) saliva. A Bombay, Le(a-b-) saliva was shown to lack Pneumococcus type XIV activity, an unusual situation, since this sample should be rich in this precursor to the ABO blood group substances. However, the sample was found to contain a new serological specificity, Le-c. It is argued that simple Mendelian inheritance does not occur with Le-c and single gene control cannot be demonstrated. Failure to repress a fetal gene at birth, as implicated by the similarity in structure between Le-c and carcinoembryonic antigen [SIMMONS and PERLMANN], has been excluded as the mechanism of inheritance of this blood group substance, due to the inability to detect carcinoembryonic antigen in the test saliva."}
{"id": "PMID:238342", "title": "Biphenyl hydroxylations and spectrally apparent interactions with liver microsomes from hamsters pre-treated with phenobarbitone and 3-methylcholanthrene.", "content": "1. Metabolism of [14-C]biphenyl by hamster liver microsomes has been studied by t.l.c., quantitative fluorimetry and difference absorption spectrophotometry. 2. 4-Hydroxybiphenyl (major metabolite) and 2-hydroxybiphenyl (minor) accounted for at least 83% of total biphenyl metabolism. Small quantities of 2,2'- and 4,4'-dihydroxybiphenyl metabolites were also tentatively identified. 3. Biphenyl 2- and 4-hydroxylations exhibited different NADPH-NADH specificities and pH profiles. 4. Phenobarbitone preferentially induced formation of 4-hydroxybiphenyl, while 3-methylcholanthrene induced 2- and 4-hydroxylation almost equally by affecting both production and further metabolism of 2- and 4-hydroxybiphenyl. 5. Biphenyl, 2- and 4-hydroxy- and 2,2'-dihydroxybiphenyl gave both high- and low-affinity type I spectrally apparent microsomal interactions, whereas 4,4'-dihydroxybiphenyl promoted a reverse type I spectral change. There was an inverse correlation between the spectral dissociation constants (Ks) and lipid solubilities for the low-affinity type I interactions and a possible direct correlation for the high-affinity type I interactions. 6. Phenobarbitone and 3-methylcholanthrene induced cytochrome P-450 and cytochrome P-448 respectively and produced complex changes in the biphenyl type I interaction kinetics. No direct relationship was found in 'control' or 'induced' microsomes between biphenyl 2- or 4-hydroxylation, the type I interaction and cytochrome P-450 concentration. The results are discussed in terms of a 3-methylcholanthrene-inducible biphenyl 2- and 4-hydroxylase and a phenobarbitone-inducible biphenyl 4-hydroxylase.", "contents": "Biphenyl hydroxylations and spectrally apparent interactions with liver microsomes from hamsters pre-treated with phenobarbitone and 3-methylcholanthrene. 1. Metabolism of [14-C]biphenyl by hamster liver microsomes has been studied by t.l.c., quantitative fluorimetry and difference absorption spectrophotometry. 2. 4-Hydroxybiphenyl (major metabolite) and 2-hydroxybiphenyl (minor) accounted for at least 83% of total biphenyl metabolism. Small quantities of 2,2'- and 4,4'-dihydroxybiphenyl metabolites were also tentatively identified. 3. Biphenyl 2- and 4-hydroxylations exhibited different NADPH-NADH specificities and pH profiles. 4. Phenobarbitone preferentially induced formation of 4-hydroxybiphenyl, while 3-methylcholanthrene induced 2- and 4-hydroxylation almost equally by affecting both production and further metabolism of 2- and 4-hydroxybiphenyl. 5. Biphenyl, 2- and 4-hydroxy- and 2,2'-dihydroxybiphenyl gave both high- and low-affinity type I spectrally apparent microsomal interactions, whereas 4,4'-dihydroxybiphenyl promoted a reverse type I spectral change. There was an inverse correlation between the spectral dissociation constants (Ks) and lipid solubilities for the low-affinity type I interactions and a possible direct correlation for the high-affinity type I interactions. 6. Phenobarbitone and 3-methylcholanthrene induced cytochrome P-450 and cytochrome P-448 respectively and produced complex changes in the biphenyl type I interaction kinetics. No direct relationship was found in 'control' or 'induced' microsomes between biphenyl 2- or 4-hydroxylation, the type I interaction and cytochrome P-450 concentration. The results are discussed in terms of a 3-methylcholanthrene-inducible biphenyl 2- and 4-hydroxylase and a phenobarbitone-inducible biphenyl 4-hydroxylase."}
{"id": "PMID:238344", "title": "Diagnosis and therapy of renal tubular acidosis in infancy.", "content": "While distrubances of the acid-base balance are frequently seen in infancy, renal tubular acidosis is a rather rare disease but should be considered as differential diagnosis if metabolic acidosis persists after adequate treatment. Proximal and distal tubular acidosis with primary and secondary forms can be differentiated. Proximal RTA is characterized by the loss of bicarbonate, distal RTA by a defect to establish a hydrogen ion gradient and thus to accomplish acidification of urine. In addition to these two basic forms a bicarbonate wasting state in distal RTA has been described. A patient with these clinical features is presented. He was admitted to our hospital at the age of 1 month with meningitis, enteritis and marked dystrophy. A persistant hyperchloraemic acidosis with concomitant hypokalaemia was present. The ammonium chloride loading test confirmed the diagnosis of primary distal RTA. Renal biopsy performed with 1 year of age revealed nephrocalcinosis of the inner medullary region of the kidney while the cortex was not affected. The patient first needed alkali doses of 12 mEq/kg/day which could be gradually reduced to 3.5 mEq/kg/day. Under additional potassium substitution of 5 mEq/kg/day he was thriving well. Differential diagnosis and the particular clinical features of this case are discussed.", "contents": "Diagnosis and therapy of renal tubular acidosis in infancy. While distrubances of the acid-base balance are frequently seen in infancy, renal tubular acidosis is a rather rare disease but should be considered as differential diagnosis if metabolic acidosis persists after adequate treatment. Proximal and distal tubular acidosis with primary and secondary forms can be differentiated. Proximal RTA is characterized by the loss of bicarbonate, distal RTA by a defect to establish a hydrogen ion gradient and thus to accomplish acidification of urine. In addition to these two basic forms a bicarbonate wasting state in distal RTA has been described. A patient with these clinical features is presented. He was admitted to our hospital at the age of 1 month with meningitis, enteritis and marked dystrophy. A persistant hyperchloraemic acidosis with concomitant hypokalaemia was present. The ammonium chloride loading test confirmed the diagnosis of primary distal RTA. Renal biopsy performed with 1 year of age revealed nephrocalcinosis of the inner medullary region of the kidney while the cortex was not affected. The patient first needed alkali doses of 12 mEq/kg/day which could be gradually reduced to 3.5 mEq/kg/day. Under additional potassium substitution of 5 mEq/kg/day he was thriving well. Differential diagnosis and the particular clinical features of this case are discussed."}
{"id": "PMID:238345", "title": "[Effect of the antiarrhythmic agent propaphenone on cardiac conduction. clinical studies using bundle of his electrography].", "content": "The influence of the new antiarrhythmic agent Propafenon on cardiac conduction and sinus node function was studied by using His-bundle recordings and atrial stimulation in 14 patients with normal and diseases conduction system. Intravenous administration of Propafenon in therapeutic dose (1-2 mg/kg) produced a significant prolongation of the atrioventricular conduction time. Increase of the A-H interval was observed in 13 of 14 subjects during sinus rhythm. Second degree A-V block (Wenckebach form) during atrial stimulation occurred at lower frequencies after administration of the drug. The impulse propagagion within the His-Purkinje system was depressed significantly (H-V interval in 8, H-S interval in 10 of 14 subjects). Propafenon did not cause any alteration in intraatrial conduction, but depression of the sinus node automaticity was noted. Total reversal of the drug induced prolonged atrioventricular conduction and a decrease of the sinus rate was seen after administration of orciprenaline. Beta-adrenergic receptor blocking and local anaesthetic direct membrane actions are discussed as possible cause of the prolongation of atrioventricular and intraventricular conduction.", "contents": "[Effect of the antiarrhythmic agent propaphenone on cardiac conduction. clinical studies using bundle of his electrography]. The influence of the new antiarrhythmic agent Propafenon on cardiac conduction and sinus node function was studied by using His-bundle recordings and atrial stimulation in 14 patients with normal and diseases conduction system. Intravenous administration of Propafenon in therapeutic dose (1-2 mg/kg) produced a significant prolongation of the atrioventricular conduction time. Increase of the A-H interval was observed in 13 of 14 subjects during sinus rhythm. Second degree A-V block (Wenckebach form) during atrial stimulation occurred at lower frequencies after administration of the drug. The impulse propagagion within the His-Purkinje system was depressed significantly (H-V interval in 8, H-S interval in 10 of 14 subjects). Propafenon did not cause any alteration in intraatrial conduction, but depression of the sinus node automaticity was noted. Total reversal of the drug induced prolonged atrioventricular conduction and a decrease of the sinus rate was seen after administration of orciprenaline. Beta-adrenergic receptor blocking and local anaesthetic direct membrane actions are discussed as possible cause of the prolongation of atrioventricular and intraventricular conduction."}
{"id": "PMID:238346", "title": "[Influence of CO2 and pH on the attachment response of the cercaria of Diplostomum spathaceum (trematoda) (author's transl)].", "content": "1. The attachment of the cercaria to artificial substrates (offered via dialyzing membranes) in definite media was investigated under conditions of variable pH and [CO2]. 2. A decrease of the pH of the substrate releases only attachments in CO2 containing media and consequently acts via CO2 systems of the medium. 3. As effective components of CO2 systems, dissolved CO2 + H2CO3 are confirmed. 4. The sensitivity of the reaction on gradients of the CO2 partial pressure (in solution) could be established by offering substrates with lowered pH in CO2 containing media. Thus, by raising the CO2 partial pressure from ca. 0,04% to 0,15% maximal fixation rates were obtained (Fig. 3). 5. The carboanhydrase inhibitor acetazolamide, when added to the medium, had no direct influence on the CO2 receptors.", "contents": "[Influence of CO2 and pH on the attachment response of the cercaria of Diplostomum spathaceum (trematoda) (author's transl)]. 1. The attachment of the cercaria to artificial substrates (offered via dialyzing membranes) in definite media was investigated under conditions of variable pH and [CO2]. 2. A decrease of the pH of the substrate releases only attachments in CO2 containing media and consequently acts via CO2 systems of the medium. 3. As effective components of CO2 systems, dissolved CO2 + H2CO3 are confirmed. 4. The sensitivity of the reaction on gradients of the CO2 partial pressure (in solution) could be established by offering substrates with lowered pH in CO2 containing media. Thus, by raising the CO2 partial pressure from ca. 0,04% to 0,15% maximal fixation rates were obtained (Fig. 3). 5. The carboanhydrase inhibitor acetazolamide, when added to the medium, had no direct influence on the CO2 receptors."}
{"id": "PMID:238347", "title": "Phosphatase systems in Paramphistomum explanatum Fischoeder, 1901.", "content": "Extracts of adult Paramphistomum explanatum have been shown to contain high concentration of acid phosphomonoesterase with maximum activity at pH 4.5. The enzyme has been characterized by an exhibition of an unexpected increase in the inhibitory action of a mercury at 1 mM concentration by EDTA. With a lower concentration of mercury (0.1 mM and below) EDTA gave partial protection against inhibition. Different concentrations of magnesium and cobalt activated the enzyme while fluoride, copper, arsenate, tartrate and p-mercuribenzoate brought about inhibition. EDTA, glycine, glutathione and sodium azide had no effect. There was an indication of the presence of alkaline phosphomonoesterase at pH 10.0. The Km for p-nitrophenyl phosphate hydrolysis was 0.45 mM at pH 4.5.", "contents": "Phosphatase systems in Paramphistomum explanatum Fischoeder, 1901. Extracts of adult Paramphistomum explanatum have been shown to contain high concentration of acid phosphomonoesterase with maximum activity at pH 4.5. The enzyme has been characterized by an exhibition of an unexpected increase in the inhibitory action of a mercury at 1 mM concentration by EDTA. With a lower concentration of mercury (0.1 mM and below) EDTA gave partial protection against inhibition. Different concentrations of magnesium and cobalt activated the enzyme while fluoride, copper, arsenate, tartrate and p-mercuribenzoate brought about inhibition. EDTA, glycine, glutathione and sodium azide had no effect. There was an indication of the presence of alkaline phosphomonoesterase at pH 10.0. The Km for p-nitrophenyl phosphate hydrolysis was 0.45 mM at pH 4.5."}
{"id": "PMID:238348", "title": "Reactions of n-hexanal with glycine in model systems.", "content": "n-Hexanal a common component of off-flavor of various foodstuffs forms in ethanol-water solutions brown coloured pigments with glycine very slowly. The changes in the ultra-violet region of spectrum, especially at the maximum at 280 nm are much quicker. Due to the fact that only the non-protonised amino acid reacts, the reaction rate is the highest in alkaline medium, especially at pH value 8.5-9. The primary product of the condensation of n-hexanal with glycine, the Schiff base, is not stable, as confirmed by the decreasing of the polarographic wave heights. The reaction rate constants of this decomposition were the highest at pH-value 8.5-9 similarly as the changes in the UV-Spectra. The effect of the temperature was negligible.", "contents": "Reactions of n-hexanal with glycine in model systems. n-Hexanal a common component of off-flavor of various foodstuffs forms in ethanol-water solutions brown coloured pigments with glycine very slowly. The changes in the ultra-violet region of spectrum, especially at the maximum at 280 nm are much quicker. Due to the fact that only the non-protonised amino acid reacts, the reaction rate is the highest in alkaline medium, especially at pH value 8.5-9. The primary product of the condensation of n-hexanal with glycine, the Schiff base, is not stable, as confirmed by the decreasing of the polarographic wave heights. The reaction rate constants of this decomposition were the highest at pH-value 8.5-9 similarly as the changes in the UV-Spectra. The effect of the temperature was negligible."}
{"id": "PMID:238349", "title": "[A modified hydroxamic acid method for the estimation of the activity of lipase (E.C. 3. 1. 1. 3)].", "content": "Optimal conditions for a modified hydroxymic acid method have been worked out with respect to the stability of the substrate emulsion; by systematically varying the ratios of the components of the solutions it was possible to develop a homogeneous reaction system which could be directly measured by spectrophotometry.", "contents": "[A modified hydroxamic acid method for the estimation of the activity of lipase (E.C. 3. 1. 1. 3)]. Optimal conditions for a modified hydroxymic acid method have been worked out with respect to the stability of the substrate emulsion; by systematically varying the ratios of the components of the solutions it was possible to develop a homogeneous reaction system which could be directly measured by spectrophotometry."}
{"id": "PMID:238352", "title": "Ribonuclease activity of Entamoeba histolytica.", "content": "Ribonuclease activity of Entamoeba histolytica was purified 65-fold by calcium phosphate gel, ammonium sulphate and acetone treatments. The enzyme was inhibited by metal ions, like Mg-2+, Mn-2+, Co-2+ and Ca-2+. Metal chelating and sulphydryl agents showed no effect. EDTA and alpha, a'-dipyridyl reversed the inhibition produced by Mg-2+, Mn-2+ and Fe-2+. Various sodium salts had negligible effect on the enzyme; however, sodium chloride activated the enzyme slightly. Amoebicidal drugs like enterovioform and chloroquine phosphate inhibited the enzyme completely, while emetine showed marked inhibitory effect. Neomycin exhibited a slight stimulatory action on this enzyme.", "contents": "Ribonuclease activity of Entamoeba histolytica. Ribonuclease activity of Entamoeba histolytica was purified 65-fold by calcium phosphate gel, ammonium sulphate and acetone treatments. The enzyme was inhibited by metal ions, like Mg-2+, Mn-2+, Co-2+ and Ca-2+. Metal chelating and sulphydryl agents showed no effect. EDTA and alpha, a'-dipyridyl reversed the inhibition produced by Mg-2+, Mn-2+ and Fe-2+. Various sodium salts had negligible effect on the enzyme; however, sodium chloride activated the enzyme slightly. Amoebicidal drugs like enterovioform and chloroquine phosphate inhibited the enzyme completely, while emetine showed marked inhibitory effect. Neomycin exhibited a slight stimulatory action on this enzyme."}
{"id": "PMID:238354", "title": "Clinical aspects of the disruptive effects of road accidents on the human body.", "content": "Knowledge of the patterns of injury from road accidents helps to reduce the risk of diagnostic error through oversight. Understanding the patterns of disruption of the body gives surgeons a better understanding of the nature of the injury and of the behaviour of the injuried tissues. This is of particular value in the diagnostic manipulation of fractures to decide whether they need internal fixation or whether external splintage will keep them in an acceptable position.", "contents": "Clinical aspects of the disruptive effects of road accidents on the human body. Knowledge of the patterns of injury from road accidents helps to reduce the risk of diagnostic error through oversight. Understanding the patterns of disruption of the body gives surgeons a better understanding of the nature of the injury and of the behaviour of the injuried tissues. This is of particular value in the diagnostic manipulation of fractures to decide whether they need internal fixation or whether external splintage will keep them in an acceptable position."}
{"id": "PMID:238358", "title": "Cerebral blood flow and oxygen consumption in the rat in hypoxic hypoxia.", "content": "In order to measure cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRo(2)) at pronounced degrees of hypoxic hypoxia the Pao(2) of artificially ventilated and normocapnic rats was reduced to between 47 and 22 mm Hg for 15-25 min with subsequent measurements of CBF, using a -133Xenon modification of the Kety and Schmidt technique, and of the arteriovenous difference in oxygen content, the venous blood being obtained from the superior sagittal sinus. When the Pao(2) was reduced to minimal values of 22 mm Hg CBF increased 4- to 6-fold, the increase in CBF being unrelated to changes in blood pressure or Paco(2). The CMRo(2) remained unchanged at all levels of hypoxia. It is concluded that the maintenance of a normal, or near-normal, cerebral energy state even at extreme degrees of hypoxic hypoxia depends solely on a homeostatic increase in CBF.", "contents": "Cerebral blood flow and oxygen consumption in the rat in hypoxic hypoxia. In order to measure cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRo(2)) at pronounced degrees of hypoxic hypoxia the Pao(2) of artificially ventilated and normocapnic rats was reduced to between 47 and 22 mm Hg for 15-25 min with subsequent measurements of CBF, using a -133Xenon modification of the Kety and Schmidt technique, and of the arteriovenous difference in oxygen content, the venous blood being obtained from the superior sagittal sinus. When the Pao(2) was reduced to minimal values of 22 mm Hg CBF increased 4- to 6-fold, the increase in CBF being unrelated to changes in blood pressure or Paco(2). The CMRo(2) remained unchanged at all levels of hypoxia. It is concluded that the maintenance of a normal, or near-normal, cerebral energy state even at extreme degrees of hypoxic hypoxia depends solely on a homeostatic increase in CBF."}
{"id": "PMID:238359", "title": "Acid-base changes and excitation-contraction coupling in rabbit myocardium. I. Effects on isometric tension development at different contraction frequencies.", "content": "The effects of changes in acid-base parameters on the active force of isolated rabbit papillary muscles were studied at contraction frequencies of 12, 60 and 120/min. When extracellular pH was lowered from 7.4 to 7.0 and 6.7 in a bathing solution buffered with 10 mM histidine, the active force decreased at all contraction frequencies studied. After parallel increases of HCO3-minus concentration (up to 47 mM) and PCO2 at a constant extracellular pH of 7.4 the active force of the muscle increased at low and decreased at high contraction frequencies. None of these effects can be attributed to catecholamine release or to altered extracellular concentration of ionized calcium. The inotropic effects produced by bicarbonate were not reproducible by methyl sulfate (47 mM) or propionate (47 mM). It is concluded that: 1. a lowering of the extracellular pH has a negative inotropic effect at all frequencies, 2. HCO3-minus has a positive inotropic effect that is most pronounced at low contraction frequencies and 3. CO2 has a negative inotropic effect exceeding that produced by the mere reduction in extracellular pH. The cellular mechanisms involved in the various inotropic effects are discussed.", "contents": "Acid-base changes and excitation-contraction coupling in rabbit myocardium. I. Effects on isometric tension development at different contraction frequencies. The effects of changes in acid-base parameters on the active force of isolated rabbit papillary muscles were studied at contraction frequencies of 12, 60 and 120/min. When extracellular pH was lowered from 7.4 to 7.0 and 6.7 in a bathing solution buffered with 10 mM histidine, the active force decreased at all contraction frequencies studied. After parallel increases of HCO3-minus concentration (up to 47 mM) and PCO2 at a constant extracellular pH of 7.4 the active force of the muscle increased at low and decreased at high contraction frequencies. None of these effects can be attributed to catecholamine release or to altered extracellular concentration of ionized calcium. The inotropic effects produced by bicarbonate were not reproducible by methyl sulfate (47 mM) or propionate (47 mM). It is concluded that: 1. a lowering of the extracellular pH has a negative inotropic effect at all frequencies, 2. HCO3-minus has a positive inotropic effect that is most pronounced at low contraction frequencies and 3. CO2 has a negative inotropic effect exceeding that produced by the mere reduction in extracellular pH. The cellular mechanisms involved in the various inotropic effects are discussed."}
{"id": "PMID:238360", "title": "Acid-base changes and excitation-contraction coupling in rabbit myocardium. II. Effects on resting membrane potential, action potential characteristics and propagation velocity.", "content": "The effects of changes in acid-base parameters on the resting membrane potential, action potential characteristics and propagation velocity were studied in isolated rabbit papillary muscles. Lowering extracellular pH from 7.4 to 6.7 in a bathing solution buffered with 10 mM histidine did not alter the resting membrane potential or action potential characteristics but casused slight reduction in propagation velocity. A parallel increase in HCO3-minus concentration (up to 47 mM)and PCO2 at a constant extracellular pH of 7.4 caused a substantial decrease in action potential duration but did not alter the resting membrane potential or propagation velocity. The decrease in action potential duration was caused by the increase in HCO3-minus concentration. Propionate (47nM) caused a shortening of the action potential which was of the same magnitude as for HCO3-minus but methylsulfate (47nM) did not have this effect. The possible influence of these changes on the inotropic state of the myocardium and the cellular mechanisms involved are discussed.", "contents": "Acid-base changes and excitation-contraction coupling in rabbit myocardium. II. Effects on resting membrane potential, action potential characteristics and propagation velocity. The effects of changes in acid-base parameters on the resting membrane potential, action potential characteristics and propagation velocity were studied in isolated rabbit papillary muscles. Lowering extracellular pH from 7.4 to 6.7 in a bathing solution buffered with 10 mM histidine did not alter the resting membrane potential or action potential characteristics but casused slight reduction in propagation velocity. A parallel increase in HCO3-minus concentration (up to 47 mM)and PCO2 at a constant extracellular pH of 7.4 caused a substantial decrease in action potential duration but did not alter the resting membrane potential or propagation velocity. The decrease in action potential duration was caused by the increase in HCO3-minus concentration. Propionate (47nM) caused a shortening of the action potential which was of the same magnitude as for HCO3-minus but methylsulfate (47nM) did not have this effect. The possible influence of these changes on the inotropic state of the myocardium and the cellular mechanisms involved are discussed."}
{"id": "PMID:238361", "title": "Adenosine triphosphate dependent calcium uptake by subcellular fractions from bovine neurohypophyses.", "content": "Bovine neurohypophyses were fractionated by differential and density gradient ultracentrifugation and the Ca-2+ uptake and ATPase activities in the microsomal, mitochondrial and secretory granule fractions were studied. The microsomal and mitochondrial fractions accumulated Ca-2+ in the presence of ATP. The accumulation by the latter per mg protein was at least twice as large as by the former. This Ca2+ accumulation was accompanied by liberation of inorganic phosphate (Pi). In the presence of sodium azide (2 mM) Ca-2+ uptake and Pi liberation were inhibited in the mitochondrial, but not in the microsomal fraction. Further studies of the microsomal fractions revealed that the ATP-dependent Ca-2+ uptake and Pi liberation activities were temperature and pH-dependent and required Mg-2+. Both activities were stimulated by very low concentrations of Ca-2+ (1-10 muM) and were inhibited by EGTA (2 mM). N-ethylmaleimide (2 mM) inhibited both the Ca-2+ uptake and ATPase activities of the microsomal fraction. These results suggest the presence of a membrane ATPase that is stimulated by both Ca-2+ and Mg-2+. It is suggested that the observed Ca-2+ uptake activities are involved in maintaining a low axoplasmic free Ca-2+ concentration, thus playing an important role in the release mechanism of vasopressin by the neurosecretory terminals.", "contents": "Adenosine triphosphate dependent calcium uptake by subcellular fractions from bovine neurohypophyses. Bovine neurohypophyses were fractionated by differential and density gradient ultracentrifugation and the Ca-2+ uptake and ATPase activities in the microsomal, mitochondrial and secretory granule fractions were studied. The microsomal and mitochondrial fractions accumulated Ca-2+ in the presence of ATP. The accumulation by the latter per mg protein was at least twice as large as by the former. This Ca2+ accumulation was accompanied by liberation of inorganic phosphate (Pi). In the presence of sodium azide (2 mM) Ca-2+ uptake and Pi liberation were inhibited in the mitochondrial, but not in the microsomal fraction. Further studies of the microsomal fractions revealed that the ATP-dependent Ca-2+ uptake and Pi liberation activities were temperature and pH-dependent and required Mg-2+. Both activities were stimulated by very low concentrations of Ca-2+ (1-10 muM) and were inhibited by EGTA (2 mM). N-ethylmaleimide (2 mM) inhibited both the Ca-2+ uptake and ATPase activities of the microsomal fraction. These results suggest the presence of a membrane ATPase that is stimulated by both Ca-2+ and Mg-2+. It is suggested that the observed Ca-2+ uptake activities are involved in maintaining a low axoplasmic free Ca-2+ concentration, thus playing an important role in the release mechanism of vasopressin by the neurosecretory terminals."}
{"id": "PMID:238362", "title": "Brain carbonic acid acidosis after acetazolamide.", "content": "In cats in barbiturate anesthesia extracellular pH and potassium were continously recorded from brian cortex by implanted microelectrodes. Implantation of the electrodes preserved the low permeability of the blood-brain-barrier to HCO3-minus and H+ions as indicated by the development of brain acidosis by I.V. injection of HCO3-minus. Acetazolamide (25 mg/kg) i.v. was followed by a marked brain acidosis which after 10 min had progressed to a drop in pH of 0.203 plus or minus 0.046 (x bar plus or minus S.D., n equals 8). The slowness ofthe development of acidosis points to a direct effect of the carbonic anhydrase inhibition on the brain tissue. As a further support for this conclusion was considered the finding of a prolonged response time of brain pH to HCO3-minus i.v. to CO2-minus inhalation, and to hyperventilation after the acetazolamide inhibtion. No changes in brain extracelllular potassium were found.", "contents": "Brain carbonic acid acidosis after acetazolamide. In cats in barbiturate anesthesia extracellular pH and potassium were continously recorded from brian cortex by implanted microelectrodes. Implantation of the electrodes preserved the low permeability of the blood-brain-barrier to HCO3-minus and H+ions as indicated by the development of brain acidosis by I.V. injection of HCO3-minus. Acetazolamide (25 mg/kg) i.v. was followed by a marked brain acidosis which after 10 min had progressed to a drop in pH of 0.203 plus or minus 0.046 (x bar plus or minus S.D., n equals 8). The slowness ofthe development of acidosis points to a direct effect of the carbonic anhydrase inhibition on the brain tissue. As a further support for this conclusion was considered the finding of a prolonged response time of brain pH to HCO3-minus i.v. to CO2-minus inhalation, and to hyperventilation after the acetazolamide inhibtion. No changes in brain extracelllular potassium were found."}
{"id": "PMID:238363", "title": "Biochemical research into psychosis.", "content": "A strategy is presented for biological psychosis research with neuroleptics acting as a point of crystallisation like antidepressants do in biological depression research. The neuroleptics chlorpromazine, haloperidol and oxypertine were studied, and it was found that they influence central catecholamine (CA) metabolism in man. An increased central dopamine (DA) turnover was found to occur in psychotic disorders, mostly in the form of motor agitation. As the first of a planned series of studies, chlorpromazine with presumed ability to reduce both DA-ergic and noradrenaline (NA)-ergic transmission and oxypertine as a more selective blocker of NA-ergic transmission were selected for comparison. The overall therapeutic effect of oxypertine was inferior to that of chlorpromazine, whereas oxypertine proved more effective in cases where loss of initiative was predominant. On the other hand, chlorpromazine exerted a more marked influence on extrapyramidal motor functions than oxypertine. In chronic psychotic disorders with inertia, oxypertine thus seems to be a neuroleptic which is strong enough to prevent exacerbation of delusions and hallucinations while at the same time increasing the level of motivation. These findings were in accordance with our predictions. The comparative study is illustrative of the practical significance of the research approach in this study: The biochemical action profile of a neuroleptic seems to be a more reliable indicator of its clinical action than does its chemical structure.", "contents": "Biochemical research into psychosis. A strategy is presented for biological psychosis research with neuroleptics acting as a point of crystallisation like antidepressants do in biological depression research. The neuroleptics chlorpromazine, haloperidol and oxypertine were studied, and it was found that they influence central catecholamine (CA) metabolism in man. An increased central dopamine (DA) turnover was found to occur in psychotic disorders, mostly in the form of motor agitation. As the first of a planned series of studies, chlorpromazine with presumed ability to reduce both DA-ergic and noradrenaline (NA)-ergic transmission and oxypertine as a more selective blocker of NA-ergic transmission were selected for comparison. The overall therapeutic effect of oxypertine was inferior to that of chlorpromazine, whereas oxypertine proved more effective in cases where loss of initiative was predominant. On the other hand, chlorpromazine exerted a more marked influence on extrapyramidal motor functions than oxypertine. In chronic psychotic disorders with inertia, oxypertine thus seems to be a neuroleptic which is strong enough to prevent exacerbation of delusions and hallucinations while at the same time increasing the level of motivation. These findings were in accordance with our predictions. The comparative study is illustrative of the practical significance of the research approach in this study: The biochemical action profile of a neuroleptic seems to be a more reliable indicator of its clinical action than does its chemical structure."}
{"id": "PMID:238365", "title": "Minoxidil--haemodynamic and clinical experiences with a new peripheral vasodilator.", "content": "Minoxidil, a new peripheral vasodilator, given orally to hypertensive men in single doses of 5-25 mg, produced no haemodynamic changes within one hour after administration. After repeated oral doses within 24 hours to a total of 15-45 mg and after 10 mg t.i.d. orally for one week, moderate decreases in BP were seen concomitant with tendencies to increased heart rate and cardiac output. Clinically, oral minoxidil 10-50 mg daily in combination with diuretics and adrenergic beta-receptor blocking agents achieved an improved BP control in five patients with sustained arterial hypertension and unsatisfactory response to previous treatment. However, in four of the five patients minoxidil had to be withdrawn because of side-effects. It is concluded that minoxidil, producing a hypotensive effect of slow onset, may find a place as a therapeutic addition to symptomatic patients with severe and therapy-resistant hypertensive cardiovascular disease, provided adequate measures are taken to counteract side-effects, especially water retention and development of oedemas.", "contents": "Minoxidil--haemodynamic and clinical experiences with a new peripheral vasodilator. Minoxidil, a new peripheral vasodilator, given orally to hypertensive men in single doses of 5-25 mg, produced no haemodynamic changes within one hour after administration. After repeated oral doses within 24 hours to a total of 15-45 mg and after 10 mg t.i.d. orally for one week, moderate decreases in BP were seen concomitant with tendencies to increased heart rate and cardiac output. Clinically, oral minoxidil 10-50 mg daily in combination with diuretics and adrenergic beta-receptor blocking agents achieved an improved BP control in five patients with sustained arterial hypertension and unsatisfactory response to previous treatment. However, in four of the five patients minoxidil had to be withdrawn because of side-effects. It is concluded that minoxidil, producing a hypotensive effect of slow onset, may find a place as a therapeutic addition to symptomatic patients with severe and therapy-resistant hypertensive cardiovascular disease, provided adequate measures are taken to counteract side-effects, especially water retention and development of oedemas."}
{"id": "PMID:238367", "title": "Formation of aberrant neurotransmitters and its implication for alcohol addiction and intoxication.", "content": "The possible involvement of false neurotransmitters in the biological aspects of addiction to alcohol has been reviewed and discussed. Current evidence is somewhat ambiguous, although suggestive, of a cause-effect relationship between possible metabolic products of biogenic amines (i.e., tetrahydroisoquinoline derivatives etc.) and addiction. A novel hypothesis of the mode of action of these derivatives developed on the basis of experiments in the reviewer's laboratory is also discussed. According to the latter hypothesis, alkaloid formation may occur in vivo at the membranous level in situ, by interaction of indoleamines and (or) catecholamines with the products of polypeptide chains and thereby modifying the properties of plasmalemmal membranes.", "contents": "Formation of aberrant neurotransmitters and its implication for alcohol addiction and intoxication. The possible involvement of false neurotransmitters in the biological aspects of addiction to alcohol has been reviewed and discussed. Current evidence is somewhat ambiguous, although suggestive, of a cause-effect relationship between possible metabolic products of biogenic amines (i.e., tetrahydroisoquinoline derivatives etc.) and addiction. A novel hypothesis of the mode of action of these derivatives developed on the basis of experiments in the reviewer's laboratory is also discussed. According to the latter hypothesis, alkaloid formation may occur in vivo at the membranous level in situ, by interaction of indoleamines and (or) catecholamines with the products of polypeptide chains and thereby modifying the properties of plasmalemmal membranes."}
{"id": "PMID:238368", "title": "Interaction of biogenic amines with ethanol.", "content": "Ethanol through its primary catabolite, acetaldehyde, competitively inhibits oxidation of aldehyde dehydrogenase substrates. As a consequence biogenic amines form increased quantities of alcohols rather than the corresponding acids. During this biotransformation, condensation reactions between deaminated and intact amines may occur which can yield tetrahydropapaverolines. These compounds are closely related to precursors of opioids which is cause to link ethanol abuse to morphine addiction. There is, however, no pharmacological or clinical evidence suggesting similarities between ethanol dependence or opiod addiction. Acetaldehyde plays an additional role in  alkaloidal formation in vitro. Biogenic amines may react with acetaldehyde to form isoquinoline or carboline compounds. Some of these substances have significant pharmacological activity. Furthermore, they may enter neural stores and displace the natural neurotransmitter. Thus, they can act as false neurotransmitters. Some investigators believe that chronic ethanol ingestion leads to significant formation of such aberrant compounds which may then upset autonomic nervous system balance. This disturbance may explain the abnormal sympathetic activity seen in withdrawal. While these ideas about the etiology of alcohol abuse have a definite appeal, they are naturally based on in vitro preliminary work. Much study of the quantitative pharmacology of these compounds in animals is required before judgement can be made as to the merits of the proposed hypotheses. In the meantime, pharmacological studies on the ability of ethanol to depress respiration in the mouse has revealed that unlike opioids or barbituates, respiratory depression induced by ethanol requires the presence in brain of serotonin. This neurotransmitter also mediates the respiratory effects of several other alcohols but curiously, not chloral hydrate, yet this compound is purported to alter biogenic amine metabolism much like ethanol. Thus, the response to ethanol can be pharmacologically separated from other major narcotic classes such as opioids and barbiturates by respiratory depression effects. The specific requirement for serotonin mediation exhibited by ethanol and several other alcohols opens the door for a rational therapeutic approach to the treatment of alcohol abuse. At the same time, this finding tends to lessen the probability that alcoholism is in some way connected with the formation of addictive alkaloids.", "contents": "Interaction of biogenic amines with ethanol. Ethanol through its primary catabolite, acetaldehyde, competitively inhibits oxidation of aldehyde dehydrogenase substrates. As a consequence biogenic amines form increased quantities of alcohols rather than the corresponding acids. During this biotransformation, condensation reactions between deaminated and intact amines may occur which can yield tetrahydropapaverolines. These compounds are closely related to precursors of opioids which is cause to link ethanol abuse to morphine addiction. There is, however, no pharmacological or clinical evidence suggesting similarities between ethanol dependence or opiod addiction. Acetaldehyde plays an additional role in  alkaloidal formation in vitro. Biogenic amines may react with acetaldehyde to form isoquinoline or carboline compounds. Some of these substances have significant pharmacological activity. Furthermore, they may enter neural stores and displace the natural neurotransmitter. Thus, they can act as false neurotransmitters. Some investigators believe that chronic ethanol ingestion leads to significant formation of such aberrant compounds which may then upset autonomic nervous system balance. This disturbance may explain the abnormal sympathetic activity seen in withdrawal. While these ideas about the etiology of alcohol abuse have a definite appeal, they are naturally based on in vitro preliminary work. Much study of the quantitative pharmacology of these compounds in animals is required before judgement can be made as to the merits of the proposed hypotheses. In the meantime, pharmacological studies on the ability of ethanol to depress respiration in the mouse has revealed that unlike opioids or barbituates, respiratory depression induced by ethanol requires the presence in brain of serotonin. This neurotransmitter also mediates the respiratory effects of several other alcohols but curiously, not chloral hydrate, yet this compound is purported to alter biogenic amine metabolism much like ethanol. Thus, the response to ethanol can be pharmacologically separated from other major narcotic classes such as opioids and barbiturates by respiratory depression effects. The specific requirement for serotonin mediation exhibited by ethanol and several other alcohols opens the door for a rational therapeutic approach to the treatment of alcohol abuse. At the same time, this finding tends to lessen the probability that alcoholism is in some way connected with the formation of addictive alkaloids."}
{"id": "PMID:238369", "title": "Microsomal ethanol oxidation: activity in vitro and in vivo.", "content": "Studies by several investigators have confirmed that the microsomal fraction of mammalian liver oxidizes ethanol to acetaldehyde in a reaction that requires NADPH and oxygen. Efforts to identify the enzymes involved have produced conflicting opinions of the reaction mechanism, however. Initially, the microsomal mixed function oxidase system was assumed to be capable of oxidizing ethanol in a mechanism that did not involve either alcohol dehydrogenase or catalase. Later evidence suggested that the oxidative enzyme was, in fact, catalase, a contaminant of microsomal preparations and that the mixed function oxidase system merely furnished hydrogen peroxide to the reaction. Much current research supports the latter interpretation. Other workers provide evidence that favors a system in which catalase does not participate. Attempts to define the reaction process have involved studies with catalase inhibitors, kinetic studies of the different reaction systems, and physical separation of catalase from the microsomal components. Questions of the mechanism of microsomal ethanol oxidation may prove to be purely academic, however. Efforts to prove that the system has significant in vivo activity generally have not been successful.", "contents": "Microsomal ethanol oxidation: activity in vitro and in vivo. Studies by several investigators have confirmed that the microsomal fraction of mammalian liver oxidizes ethanol to acetaldehyde in a reaction that requires NADPH and oxygen. Efforts to identify the enzymes involved have produced conflicting opinions of the reaction mechanism, however. Initially, the microsomal mixed function oxidase system was assumed to be capable of oxidizing ethanol in a mechanism that did not involve either alcohol dehydrogenase or catalase. Later evidence suggested that the oxidative enzyme was, in fact, catalase, a contaminant of microsomal preparations and that the mixed function oxidase system merely furnished hydrogen peroxide to the reaction. Much current research supports the latter interpretation. Other workers provide evidence that favors a system in which catalase does not participate. Attempts to define the reaction process have involved studies with catalase inhibitors, kinetic studies of the different reaction systems, and physical separation of catalase from the microsomal components. Questions of the mechanism of microsomal ethanol oxidation may prove to be purely academic, however. Efforts to prove that the system has significant in vivo activity generally have not been successful."}
{"id": "PMID:238372", "title": "Four patterns of perinatal brain damage and their conditions of occurrence in primates.", "content": "The findings described in the present study are summarized in Table 1. It may be noted that anoxia or total asphyxia, whether in the newborn animal or in the (see article) adult, leads to patterns of injury in the brainstem. Hemispheral structures outside the thalamus seem to be entirely spared in those animals which survive. In contrast to this, situations leading to hypoxia associated with severe acidosis, usually of a mixed respiratory and metabolic type, cause brain edema; and when the edema is limited in its distribution, the damage is restricted to specific cortical loci. When the cerebral edema becomes more generalized owing to spread of the process, more and more extensive regions of the hemispheres are damaged until the entire cerebrum may become necrotic. On the other hand, clinical circumstances which lead to hypoxia but without acidosis of any great magnitude--usually due to the indolence of the process or to an associated hyperventilation of the mother--produce lesions which may be restricted to the white matter. These processes may be characterized by perivenular white matter hemorrhage and/or focal areas of periventricular leucomalacia. Finally, those clinical circumstances which lead to combined episodes of hypoxia plus anoxia with acidosis favor a predominance of lesions that affect the basal ganglia.", "contents": "Four patterns of perinatal brain damage and their conditions of occurrence in primates. The findings described in the present study are summarized in Table 1. It may be noted that anoxia or total asphyxia, whether in the newborn animal or in the (see article) adult, leads to patterns of injury in the brainstem. Hemispheral structures outside the thalamus seem to be entirely spared in those animals which survive. In contrast to this, situations leading to hypoxia associated with severe acidosis, usually of a mixed respiratory and metabolic type, cause brain edema; and when the edema is limited in its distribution, the damage is restricted to specific cortical loci. When the cerebral edema becomes more generalized owing to spread of the process, more and more extensive regions of the hemispheres are damaged until the entire cerebrum may become necrotic. On the other hand, clinical circumstances which lead to hypoxia but without acidosis of any great magnitude--usually due to the indolence of the process or to an associated hyperventilation of the mother--produce lesions which may be restricted to the white matter. These processes may be characterized by perivenular white matter hemorrhage and/or focal areas of periventricular leucomalacia. Finally, those clinical circumstances which lead to combined episodes of hypoxia plus anoxia with acidosis favor a predominance of lesions that affect the basal ganglia."}
{"id": "PMID:238383", "title": "Vitamin E status of Alaskan Eskimos.", "content": "A survey was conducted during 1971-1973 on the vitamin E status of Alaskan Eskomos. The subjects were 315 residents of the northern coastal villages of Wainwright and Point Hope and the southwestern inland villages of Kasigluk and Nunapitchuk. Plasma vitamin E levels for the 6- to 17-year-old subjects at Wainwright, Point Hope, and Nunapitchuk were 0.81 plus or minus 0.26, 0.90 plus or minus 0.20, and 0.84 plus or minus 0.25 mg/100 ml (mean and standard deviation), respectively. The values for adults at Wainwright, Point Hope, and Kasigluk were 1.23 plus or minus 0.27, 1.23 plus or minus 0.27, and 1.27 plus or minus 0.33 mg/100 ml, respectively. No value less than 0.30 mg/100 ml was observed. Alpha-tocopherol was the only isomer present in significant amounts. Plasma vitamin E levels did not change significantly between 6 and 17 years of age; however, a steady increase with age was observed in the 18- to 69-year-old groups. Plasma alpha-tocopherol concentrations were significantly lower in children than in adults but there were no differences attributable to sex or geographic location. Vitamin E concentration in the blood plasma was linearly correlated with cholesterol concentration. Values are reported for the vitamin E content of some native foods. This study indicates that plasma vitamin E levels in Alaskan Eskimos consuming a high meat or fish diet are comparable to those in adults of the United States consuming a mixed diet.", "contents": "Vitamin E status of Alaskan Eskimos. A survey was conducted during 1971-1973 on the vitamin E status of Alaskan Eskomos. The subjects were 315 residents of the northern coastal villages of Wainwright and Point Hope and the southwestern inland villages of Kasigluk and Nunapitchuk. Plasma vitamin E levels for the 6- to 17-year-old subjects at Wainwright, Point Hope, and Nunapitchuk were 0.81 plus or minus 0.26, 0.90 plus or minus 0.20, and 0.84 plus or minus 0.25 mg/100 ml (mean and standard deviation), respectively. The values for adults at Wainwright, Point Hope, and Kasigluk were 1.23 plus or minus 0.27, 1.23 plus or minus 0.27, and 1.27 plus or minus 0.33 mg/100 ml, respectively. No value less than 0.30 mg/100 ml was observed. Alpha-tocopherol was the only isomer present in significant amounts. Plasma vitamin E levels did not change significantly between 6 and 17 years of age; however, a steady increase with age was observed in the 18- to 69-year-old groups. Plasma alpha-tocopherol concentrations were significantly lower in children than in adults but there were no differences attributable to sex or geographic location. Vitamin E concentration in the blood plasma was linearly correlated with cholesterol concentration. Values are reported for the vitamin E content of some native foods. This study indicates that plasma vitamin E levels in Alaskan Eskimos consuming a high meat or fish diet are comparable to those in adults of the United States consuming a mixed diet."}
{"id": "PMID:238384", "title": "Inhibitory effect of L-glutamine on gastric irritation and back diffusion of gastric acid in response to aspirin in the rat.", "content": "L-Glutamine given orally at 750 mg/kg significantly reduced the formation of gastric mucosal lesions induced by aspirin at 100 mg/kg at 1, 3, and 7 hours in pylorus-ligated rats. L-Glutamine markedly inhibited the loss of H+ and a corresponding increment of Na+ through the aspirin-damaged mucosal barrier, which suggests inhibition of acid back diffusion as the mechanism of action. In vagotomized rats, the diffusion of H+ from the instilled acid solution into the gastric mucosa and outflux of Na+ from the mucosa into the lumen was so strong that aspirin could not show any acceleration of a back diffusion of H+ in contrast to the aspirin-free group. However, L-Glutamine given with or without aspirin inhibited the group. However, L-Glutamine given with or without aspirin inhibited the back diffusion of H+ instilled into the vagotomized rat stomach.", "contents": "Inhibitory effect of L-glutamine on gastric irritation and back diffusion of gastric acid in response to aspirin in the rat. L-Glutamine given orally at 750 mg/kg significantly reduced the formation of gastric mucosal lesions induced by aspirin at 100 mg/kg at 1, 3, and 7 hours in pylorus-ligated rats. L-Glutamine markedly inhibited the loss of H+ and a corresponding increment of Na+ through the aspirin-damaged mucosal barrier, which suggests inhibition of acid back diffusion as the mechanism of action. In vagotomized rats, the diffusion of H+ from the instilled acid solution into the gastric mucosa and outflux of Na+ from the mucosa into the lumen was so strong that aspirin could not show any acceleration of a back diffusion of H+ in contrast to the aspirin-free group. However, L-Glutamine given with or without aspirin inhibited the group. However, L-Glutamine given with or without aspirin inhibited the back diffusion of H+ instilled into the vagotomized rat stomach."}
{"id": "PMID:238386", "title": "Hepatitis-B-antigenemia with panarteritis, diffuse proliferative glomerulitis and malignant hypertension.", "content": "Fatal, rapidly progressive malignant hypertension, progressive renal failure and radiographic evidence of diffuse angitis, with persistent hepatitis-B-antigenemia, in a young man during his early recovery from documented type B viral hepatitis, is presented. At postmortem there was both light and electron microscopic evidence of systemic arteritis and proliferative glomerulonephritis.", "contents": "Hepatitis-B-antigenemia with panarteritis, diffuse proliferative glomerulitis and malignant hypertension. Fatal, rapidly progressive malignant hypertension, progressive renal failure and radiographic evidence of diffuse angitis, with persistent hepatitis-B-antigenemia, in a young man during his early recovery from documented type B viral hepatitis, is presented. At postmortem there was both light and electron microscopic evidence of systemic arteritis and proliferative glomerulonephritis."}
{"id": "PMID:238387", "title": "Technetium-99m: basic nuclear physics and chemical properties.", "content": "The nuclear physics and chemical properties of technetium-99m are reviewed. The review of basic nuclear physics includes: classification of nuclides, nuclear stability, production of radionuclides, artificial production of molybdenum-99, production of technetium 99m and -99Mo-99mTc generators. The discussion of the chemistry of technetium includes a profile of several -99mCc-labeled radiopharmaceuticals.", "contents": "Technetium-99m: basic nuclear physics and chemical properties. The nuclear physics and chemical properties of technetium-99m are reviewed. The review of basic nuclear physics includes: classification of nuclides, nuclear stability, production of radionuclides, artificial production of molybdenum-99, production of technetium 99m and -99Mo-99mTc generators. The discussion of the chemistry of technetium includes a profile of several -99mCc-labeled radiopharmaceuticals."}
{"id": "PMID:238388", "title": "Pharmacotherapy of essential hypertension.", "content": "Practical clinical aspects of the evaluation and treatment of essential hypertension are reviewed. Drug therapy discussed includes diuretics, and as adjunctive therapy, sympathoplegic agents, peripheral vasodilators and beta blockers. Also covered are treatment of less common forms of essential hypertension, other forms of antihypertensive therapy, and the use of fixed combinations of antihypertensive drugs.", "contents": "Pharmacotherapy of essential hypertension. Practical clinical aspects of the evaluation and treatment of essential hypertension are reviewed. Drug therapy discussed includes diuretics, and as adjunctive therapy, sympathoplegic agents, peripheral vasodilators and beta blockers. Also covered are treatment of less common forms of essential hypertension, other forms of antihypertensive therapy, and the use of fixed combinations of antihypertensive drugs."}
{"id": "PMID:238389", "title": "Extemporaneous preparation of methyldopa in two syrup vehicles.", "content": "The stability of methyldopa in two extemporaneous syrup preparations was studied. Film-coated methyldopa tablets were triturated and incorporated into (1) unpreserved Syrup USP and (2) an equal mixture of simple syrup containing 0.5% citric acid and 0.2 N hydrochloric acid, in concentrations of 50 mg/ml. The preparations were stored in the dark, for 14 days at 5 C and 25 C. Samples were analyzed spectrophotometrically for methyldopa content at various intervals. Both preparations were stable under the conditions studied.", "contents": "Extemporaneous preparation of methyldopa in two syrup vehicles. The stability of methyldopa in two extemporaneous syrup preparations was studied. Film-coated methyldopa tablets were triturated and incorporated into (1) unpreserved Syrup USP and (2) an equal mixture of simple syrup containing 0.5% citric acid and 0.2 N hydrochloric acid, in concentrations of 50 mg/ml. The preparations were stored in the dark, for 14 days at 5 C and 25 C. Samples were analyzed spectrophotometrically for methyldopa content at various intervals. Both preparations were stable under the conditions studied."}
{"id": "PMID:238390", "title": "Properties of mannitol injection (25%) after repeated autoclavings.", "content": "The physical and chemical properties of mannitol injection 25% were examined after repeated autoclavings.  The product was found to be stable after five autoclavings of 250 F for 15 minutes each.  No extracts from the rubber closures were found.  It is advised that the product may be repeatedly heated or autoclaved if crystals appear as a result of storage.", "contents": "Properties of mannitol injection (25%) after repeated autoclavings. The physical and chemical properties of mannitol injection 25% were examined after repeated autoclavings.  The product was found to be stable after five autoclavings of 250 F for 15 minutes each.  No extracts from the rubber closures were found.  It is advised that the product may be repeatedly heated or autoclaved if crystals appear as a result of storage."}
{"id": "PMID:238392", "title": "The acid-base and biochemical characteristics of intrapartum fetal asphyxia.", "content": "The maternal and fetal acid-base, lactate, and pyruvate characteristics during the course of labor and at delivery were studied in 124 patients delivered of an infant with evidence of metabolic acidosis at delivery. This metabolic acidosis is principally caused by hyperlactatemia resulting from the tissue oxygen debt accompanying fetal asphyxia. Hypoxemia was one mechanism contributing to this fetal asphyxia and tissue oxygen debt. This evidence of fetal asphyxia developed during the last half and principally during the last two hours of the intrapartum period. Acid-base assessment of fetal blood with identification of a metabolic acidosis will provide an accurate objective diagnosis of intrapartum fetal asphyxia.", "contents": "The acid-base and biochemical characteristics of intrapartum fetal asphyxia. The maternal and fetal acid-base, lactate, and pyruvate characteristics during the course of labor and at delivery were studied in 124 patients delivered of an infant with evidence of metabolic acidosis at delivery. This metabolic acidosis is principally caused by hyperlactatemia resulting from the tissue oxygen debt accompanying fetal asphyxia. Hypoxemia was one mechanism contributing to this fetal asphyxia and tissue oxygen debt. This evidence of fetal asphyxia developed during the last half and principally during the last two hours of the intrapartum period. Acid-base assessment of fetal blood with identification of a metabolic acidosis will provide an accurate objective diagnosis of intrapartum fetal asphyxia."}
{"id": "PMID:238393", "title": "Clinical characteristics of pregnancies complicated by intrapartum fetal asphyxia.", "content": "The clinical characteristics of 124 pregnancies complicated by intrapartum fetal asphyxia have been reviewed. The evidence of fetal asphyxia tends to appear earlier in patients with maternal medical and obstetric complications than in those with labor complications. Evidence of clinical fetal distress was present in 36 per cent and was not related to the severity of the asphyxia. Low Apgar scores occurred in 40 per cent of infants with moderate asphyxia and in 80 per cent of infants with severe asphyxia at delivery. In the newborn infants, clinical evidence of cerebral abnormality was observed in 3 per cent, and evidence of the respiratory distress syndrome was seen in 3 per cent of the study group.", "contents": "Clinical characteristics of pregnancies complicated by intrapartum fetal asphyxia. The clinical characteristics of 124 pregnancies complicated by intrapartum fetal asphyxia have been reviewed. The evidence of fetal asphyxia tends to appear earlier in patients with maternal medical and obstetric complications than in those with labor complications. Evidence of clinical fetal distress was present in 36 per cent and was not related to the severity of the asphyxia. Low Apgar scores occurred in 40 per cent of infants with moderate asphyxia and in 80 per cent of infants with severe asphyxia at delivery. In the newborn infants, clinical evidence of cerebral abnormality was observed in 3 per cent, and evidence of the respiratory distress syndrome was seen in 3 per cent of the study group."}
{"id": "PMID:238395", "title": "Response of the primate fetus to intra-amniotic saline injection.", "content": "The amniotic fluid was replaced with 20 per cent sodium chloride solution during the second half of gestation in 12 pregnant rhesus monkeys. This produced a congealing of the fetal blood in the small umbilical vessels which overlie in the placental chorionic plate. Death of severe asphyxia followed within 20 to 50 minutes in the younger fetuses due to a prompt cessation of umbilical blood flow. During this time, the rise in serum sodium of the fetus was moderate and could not be implicated as the cause of fetal death. In older fetuses, the asphyxia produced by the saline injection was transient and less severe, occasionally permitting survival. The caliber of the affected fetal umbilical blood vessels and their blood flow rates are presented as the principal determinants of the rapidity of development and the severity of the asphyxia produced by saline instillation.", "contents": "Response of the primate fetus to intra-amniotic saline injection. The amniotic fluid was replaced with 20 per cent sodium chloride solution during the second half of gestation in 12 pregnant rhesus monkeys. This produced a congealing of the fetal blood in the small umbilical vessels which overlie in the placental chorionic plate. Death of severe asphyxia followed within 20 to 50 minutes in the younger fetuses due to a prompt cessation of umbilical blood flow. During this time, the rise in serum sodium of the fetus was moderate and could not be implicated as the cause of fetal death. In older fetuses, the asphyxia produced by the saline injection was transient and less severe, occasionally permitting survival. The caliber of the affected fetal umbilical blood vessels and their blood flow rates are presented as the principal determinants of the rapidity of development and the severity of the asphyxia produced by saline instillation."}
{"id": "PMID:238396", "title": "Significance of meconium during labor.", "content": "Continuous fetal heart rate (FHR) monitoring and routine fetal scalp blood sampling was utilized in the evaluations of 366 fetuses during labor. One hundred and six patients had meconium in the amniotic fluid at some time during labor. A total of 26,110 uterine contractions were monitored during these 366 labors. The incidence of FHR patterns as a percentage of uterine contractions was calculated for the meconium and nonmeconium groups. Although there was a 3 1/2-fold increase in the incidence of low five-minute Apgar scores (less than 7) in the meconium group, signs of fetal distress were, with rare esception, not significantly different from those in the nonmeconium group. The presence of meconium in the amniotic fluid without signs of fetal asphyxia (late decelerations and acidosis) is not a sign of fetal distress and need not be an indication for active intervention. The combination of fetal asphyxia and meconium staining of the amniotic fluid, however, does enhance the potential for meconium aspiration and a poor neonatal outcome. Universal fetal heart rate monitoring and appropriate fetal acid-base evaluation is recommended for following patients with meconium in the amniotic fluid during labor.", "contents": "Significance of meconium during labor. Continuous fetal heart rate (FHR) monitoring and routine fetal scalp blood sampling was utilized in the evaluations of 366 fetuses during labor. One hundred and six patients had meconium in the amniotic fluid at some time during labor. A total of 26,110 uterine contractions were monitored during these 366 labors. The incidence of FHR patterns as a percentage of uterine contractions was calculated for the meconium and nonmeconium groups. Although there was a 3 1/2-fold increase in the incidence of low five-minute Apgar scores (less than 7) in the meconium group, signs of fetal distress were, with rare esception, not significantly different from those in the nonmeconium group. The presence of meconium in the amniotic fluid without signs of fetal asphyxia (late decelerations and acidosis) is not a sign of fetal distress and need not be an indication for active intervention. The combination of fetal asphyxia and meconium staining of the amniotic fluid, however, does enhance the potential for meconium aspiration and a poor neonatal outcome. Universal fetal heart rate monitoring and appropriate fetal acid-base evaluation is recommended for following patients with meconium in the amniotic fluid during labor."}
{"id": "PMID:238397", "title": "Placental transport of alcohol and its effect on maternal and fetal acid-base balance.", "content": "The placental transport of alcohol and its effect on maternal and fetal acid-base balance studied in 10 sheep experiments by the maternal infusion of a 9.75 per cent solution of alcohol-dextrose at a rate of 15 c.c. per kilogram for 1 or 2 hours. Serial maternal and fetal blood sampling during and following the alcohol infusion revealed rapid placental diffusion of alcohol, a highly significant correlation between maternal and fetal blood alcohol concentrations, and a similar peak concentration of approximately 0.230 Gm. per 100 ml. in maternal and fetal blood that differed only in time of onset during the 1 and 2 hour infusion periods. Blood alcohol concentrations remained high for several hours during the postinfusion period. A significant maternal hyperlactacidemia and hyperglycemia were noted but did not result in significant alterations in maternal acid-base balance. An initial fetal metabolic acidosis and later mixed acidosis were observed during the alcohol infusion and worsened during the postinfusion period.", "contents": "Placental transport of alcohol and its effect on maternal and fetal acid-base balance. The placental transport of alcohol and its effect on maternal and fetal acid-base balance studied in 10 sheep experiments by the maternal infusion of a 9.75 per cent solution of alcohol-dextrose at a rate of 15 c.c. per kilogram for 1 or 2 hours. Serial maternal and fetal blood sampling during and following the alcohol infusion revealed rapid placental diffusion of alcohol, a highly significant correlation between maternal and fetal blood alcohol concentrations, and a similar peak concentration of approximately 0.230 Gm. per 100 ml. in maternal and fetal blood that differed only in time of onset during the 1 and 2 hour infusion periods. Blood alcohol concentrations remained high for several hours during the postinfusion period. A significant maternal hyperlactacidemia and hyperglycemia were noted but did not result in significant alterations in maternal acid-base balance. An initial fetal metabolic acidosis and later mixed acidosis were observed during the alcohol infusion and worsened during the postinfusion period."}
{"id": "PMID:238398", "title": "The use of 50 per cent phosphoric acid as an etching agent in orthodontics: a rational approach.", "content": "The chemical treatment of enamel surfaces is an approach used in obtaining increased adhesion of dental materials to tooth surfaces. One of the conditioning solutions extensively used prior to the direct bonding of orthodontic attachments is a 50 per cent phosphoric acid solution. The object of this investigation was to study the effect of various concentrations of phosphoric acid on the bond strength of an epoxy adhesive formulation developed for the direct bonding of orthodontic attachments. Furthermore, an attempt was made to quantitate the etching action of the phosphoric acid solutions by determining the depth of etch on polished enamel surfaces and recording the surface profiles of etched enamel surfaces by means of a surface-roughness measuring instrument. The use of 50 per cent phosphoric acid solution as a conditioning agent prior to the use of the epoxy adhesive formulation is advocated. The rationale supporting this recommendation includes (1) the bond strength of the epoxy adhesive system to enamel surfaces etched with 50 per cent H3PO4 is not significantly improved by the use of phosphoric acid at any other concentration; (2) the depth of etch obtained with 50 per cent H3PO4 is less than that observed with H3PO4 solution at concentrations which produce comparable bond strengths; (3) the surface roughness of enamel surfaces etched with 50 per cent H3PO4 is greater than that obtained with more dilute acid solutions. The optimal phosphoric acid concentration should be determined for each adhesive system.", "contents": "The use of 50 per cent phosphoric acid as an etching agent in orthodontics: a rational approach. The chemical treatment of enamel surfaces is an approach used in obtaining increased adhesion of dental materials to tooth surfaces. One of the conditioning solutions extensively used prior to the direct bonding of orthodontic attachments is a 50 per cent phosphoric acid solution. The object of this investigation was to study the effect of various concentrations of phosphoric acid on the bond strength of an epoxy adhesive formulation developed for the direct bonding of orthodontic attachments. Furthermore, an attempt was made to quantitate the etching action of the phosphoric acid solutions by determining the depth of etch on polished enamel surfaces and recording the surface profiles of etched enamel surfaces by means of a surface-roughness measuring instrument. The use of 50 per cent phosphoric acid solution as a conditioning agent prior to the use of the epoxy adhesive formulation is advocated. The rationale supporting this recommendation includes (1) the bond strength of the epoxy adhesive system to enamel surfaces etched with 50 per cent H3PO4 is not significantly improved by the use of phosphoric acid at any other concentration; (2) the depth of etch obtained with 50 per cent H3PO4 is less than that observed with H3PO4 solution at concentrations which produce comparable bond strengths; (3) the surface roughness of enamel surfaces etched with 50 per cent H3PO4 is greater than that obtained with more dilute acid solutions. The optimal phosphoric acid concentration should be determined for each adhesive system."}
{"id": "PMID:238399", "title": "Soteria: Evaluation of a home-based treatment for schizophrenia.", "content": "Data are reported from an ongoing study comparing outcome in two groups of young, first-admission schizophrenics - one receiving \"usual\" treatment (including drugs) on the wards of a good community mental health center, the other being treated by a non-professional staff (usually without phenothiazines) in a small home-like facility in the community. Six-month and one-year outcome data show few differences in symptoms between the two groups, but three measures of psychosocial functioning significantly favor the experimental group.", "contents": "Soteria: Evaluation of a home-based treatment for schizophrenia. Data are reported from an ongoing study comparing outcome in two groups of young, first-admission schizophrenics - one receiving \"usual\" treatment (including drugs) on the wards of a good community mental health center, the other being treated by a non-professional staff (usually without phenothiazines) in a small home-like facility in the community. Six-month and one-year outcome data show few differences in symptoms between the two groups, but three measures of psychosocial functioning significantly favor the experimental group."}
{"id": "PMID:238400", "title": "Mitochondrial permeability to chloride ion.", "content": "It is generally accepted that the inner membrane of the mitchondrion is not penetrated by chloride ion, in contrast to other biological membranes which are chloride permeable. In this report mitochondrial permeablity to chloride ion has been reevaluated by the measurement of passive swelling in isotonic chloride-containing solutions in the presence of an uncoupling agent. Under these conditions, mitochondria prepared from rat liver or beef heart show a definite uptake of wide variety of chloride salts. Mitochondrial chloride transport appears to be electrogenic, as is the transmembrane movement of the other halides. Therefore, the mitochondrial inner membrane shares with other biological membranes a definite permeability to this ubiquitous anion.", "contents": "Mitochondrial permeability to chloride ion. It is generally accepted that the inner membrane of the mitchondrion is not penetrated by chloride ion, in contrast to other biological membranes which are chloride permeable. In this report mitochondrial permeablity to chloride ion has been reevaluated by the measurement of passive swelling in isotonic chloride-containing solutions in the presence of an uncoupling agent. Under these conditions, mitochondria prepared from rat liver or beef heart show a definite uptake of wide variety of chloride salts. Mitochondrial chloride transport appears to be electrogenic, as is the transmembrane movement of the other halides. Therefore, the mitochondrial inner membrane shares with other biological membranes a definite permeability to this ubiquitous anion."}
{"id": "PMID:238401", "title": "Transport of H plus and other electrolytes across isolated gastric mucosa of the rabbit.", "content": "The relationship of transmural and cellular phenomena to the rate of spontaneous luminal HH+ secretion by short-circuited gastric mucosa bathed in HCO3- and CO2-free Ringer solution was studied by the pH-stat technique. The bulk of luminal acidification can be accounted for by the appearance of H+ and not by organic acids. Acid secretion requires the presence of O2 and exogenous substrate but is not limited by endogenous CO2 production. The rate of H+ secretion is matched by the serosal appearance of alkali. The greater appearance of CO2 on the serosal side of the mucosa is consistent with hydroxylation of CO2 and greater permeability of the serosal border to HCO3-. Luminal changes in H+ concentrations affect H+ secretion but serosal changes do not, suggesting that the gradient produced by H+ secretion is at the luminal border. Steady-state isotopic Na+ and Cl- fluxes indicate net secretion of both ions, but net K+ transport is negligible.", "contents": "Transport of H plus and other electrolytes across isolated gastric mucosa of the rabbit. The relationship of transmural and cellular phenomena to the rate of spontaneous luminal HH+ secretion by short-circuited gastric mucosa bathed in HCO3- and CO2-free Ringer solution was studied by the pH-stat technique. The bulk of luminal acidification can be accounted for by the appearance of H+ and not by organic acids. Acid secretion requires the presence of O2 and exogenous substrate but is not limited by endogenous CO2 production. The rate of H+ secretion is matched by the serosal appearance of alkali. The greater appearance of CO2 on the serosal side of the mucosa is consistent with hydroxylation of CO2 and greater permeability of the serosal border to HCO3-. Luminal changes in H+ concentrations affect H+ secretion but serosal changes do not, suggesting that the gradient produced by H+ secretion is at the luminal border. Steady-state isotopic Na+ and Cl- fluxes indicate net secretion of both ions, but net K+ transport is negligible."}
{"id": "PMID:238402", "title": "Mechanisms of acid disposal in canine duodenum.", "content": "Distal duodenal pouches chronically excluded from the intestinal stream were perfused in seven awake dogs by a constant-circulation technique using isomolar solutions containing 60-120 mM HCl. The rate of disappearance of hydrogen ions (H+) and net ion movements was measured. In all experiments there was a loss of H+ from the perfusate accompanied by a gain of sodium (Na+), potassium (K+) and chloride (Cl-), together with an increase in volume and a decrease in osmolality. The magnitude of this H+ loss was a function of instillate [H+]. The H+ lost by neutralization was separated from that lost by diffusion by calculations based on the assumption that the observed changes in somolality were the result of neutralization by bicarbonate (HCO3-). The bulk of the acid (67%) was lost by neutralization, the remainder back-diffusing in a one-to-one exchange for diffusable Na+. This ability to dispose of acid decreased with increasing age of the pouches due to a diminished volume of HCO3- secretion, the magnitude lost by backdiffusion remaining unchanged.", "contents": "Mechanisms of acid disposal in canine duodenum. Distal duodenal pouches chronically excluded from the intestinal stream were perfused in seven awake dogs by a constant-circulation technique using isomolar solutions containing 60-120 mM HCl. The rate of disappearance of hydrogen ions (H+) and net ion movements was measured. In all experiments there was a loss of H+ from the perfusate accompanied by a gain of sodium (Na+), potassium (K+) and chloride (Cl-), together with an increase in volume and a decrease in osmolality. The magnitude of this H+ loss was a function of instillate [H+]. The H+ lost by neutralization was separated from that lost by diffusion by calculations based on the assumption that the observed changes in somolality were the result of neutralization by bicarbonate (HCO3-). The bulk of the acid (67%) was lost by neutralization, the remainder back-diffusing in a one-to-one exchange for diffusable Na+. This ability to dispose of acid decreased with increasing age of the pouches due to a diminished volume of HCO3- secretion, the magnitude lost by backdiffusion remaining unchanged."}
{"id": "PMID:238403", "title": "Effect of histamine on microvasculature of isolated dog gracilis muscle.", "content": "Isogravimetric capillary pressure (Pci), capillary filtration coefficient (CFC), and plasma protein concentration were measured before and during adminisistration of histamine in an isolated, independently perfused canine gracilis muscle. Histamine produced an average decrease in Pci of 14.1 mmHg, an increase in CFC of 36-fold, and an increased rate of plasma protein escape of at least 24-fold. These results suggest that histamine reduces the reflection coefficient for protein at the capillary wall and are consistent with predictions of the theory of restricted diffusion assuming that 1-2.5% of available pores increase in radious from 40 to 240 A.", "contents": "Effect of histamine on microvasculature of isolated dog gracilis muscle. Isogravimetric capillary pressure (Pci), capillary filtration coefficient (CFC), and plasma protein concentration were measured before and during adminisistration of histamine in an isolated, independently perfused canine gracilis muscle. Histamine produced an average decrease in Pci of 14.1 mmHg, an increase in CFC of 36-fold, and an increased rate of plasma protein escape of at least 24-fold. These results suggest that histamine reduces the reflection coefficient for protein at the capillary wall and are consistent with predictions of the theory of restricted diffusion assuming that 1-2.5% of available pores increase in radious from 40 to 240 A."}
{"id": "PMID:238404", "title": "Anion effects on cation movements during correction of potassium depletion.", "content": "The differential effects of KCl vs. KHCO3 for intravenous K+ repletion were evaluated in a series of nephrectomized dogs previously depleted of 20% of total-body K by a 2-wk regimen consisting of K-free diet plus DOCA plus chlorothiazide. Twenty-four percent of K losses (5% of original TBK) were replaced by a 2-h infusion of either CKl or KHCO3. Blood pH was maintained at normal levels by controlling the rate of respiration. Skeletal muscle biopsies were taken before and 2 h after repletion, and blood samples were taken at intervals throughout. The following differences resulting from KHCO3 compared to KCl repletion were found: a) a greater cellular K uptake, a lower rate of increase, and a lower steady-state extracellular K+ concentration; b) a less increase in intracellular K+ concentration and a less decrease in intracellular Na+ concentration. These differences, which were independent of extracellular pH or kidney function, are thought to be secondary to unequal distribution of Cl- and HCO3-ions.", "contents": "Anion effects on cation movements during correction of potassium depletion. The differential effects of KCl vs. KHCO3 for intravenous K+ repletion were evaluated in a series of nephrectomized dogs previously depleted of 20% of total-body K by a 2-wk regimen consisting of K-free diet plus DOCA plus chlorothiazide. Twenty-four percent of K losses (5% of original TBK) were replaced by a 2-h infusion of either CKl or KHCO3. Blood pH was maintained at normal levels by controlling the rate of respiration. Skeletal muscle biopsies were taken before and 2 h after repletion, and blood samples were taken at intervals throughout. The following differences resulting from KHCO3 compared to KCl repletion were found: a) a greater cellular K uptake, a lower rate of increase, and a lower steady-state extracellular K+ concentration; b) a less increase in intracellular K+ concentration and a less decrease in intracellular Na+ concentration. These differences, which were independent of extracellular pH or kidney function, are thought to be secondary to unequal distribution of Cl- and HCO3-ions."}
{"id": "PMID:238405", "title": "Interaction of O2 and CO2 in sustained exercise hyperemia of canine skeletal muscle.", "content": "The relative contribution of O2 and CO2 to the metabolic control of blood flow in long-term exercise was examined in the denervated gracilis muscle of the anesthetized dog. The data show that 1) on initiation of heavy exercise, the effluent blood PO2 and pH fall markedly and then rise slowly but remain depressed relative to control during 60 min of exercise hyperemia, while the initial increases in [K+] and osmolality rapidly approach and eventually reach preexercise levels. 2) The enhanced vasodilator activity of venous blood from exercising muscle is attenuated when effluent blood PO2 or pH is corrected to preexercise levels; it is completely abolished when both are corrected. 3) Induced reduction PO2 or pH in the arterial inflow, and thus venous outflow, of resting muscle produces a fall in resistance; simultaneous reductions of both to levels seen in heavy exercise produce a fall in resistance to near that observed during exercise. Since the enhanced vasodilator activity of venous blood from the contracting muscle was abolished by simultaneous correction of the PO2 and pH, it seems likely that these factors, acting directly or indirectly, are the principal chemicals responsible for the maintenance of the vasodilation seen in canine skeletal muscle during heavy exercise.", "contents": "Interaction of O2 and CO2 in sustained exercise hyperemia of canine skeletal muscle. The relative contribution of O2 and CO2 to the metabolic control of blood flow in long-term exercise was examined in the denervated gracilis muscle of the anesthetized dog. The data show that 1) on initiation of heavy exercise, the effluent blood PO2 and pH fall markedly and then rise slowly but remain depressed relative to control during 60 min of exercise hyperemia, while the initial increases in [K+] and osmolality rapidly approach and eventually reach preexercise levels. 2) The enhanced vasodilator activity of venous blood from exercising muscle is attenuated when effluent blood PO2 or pH is corrected to preexercise levels; it is completely abolished when both are corrected. 3) Induced reduction PO2 or pH in the arterial inflow, and thus venous outflow, of resting muscle produces a fall in resistance; simultaneous reductions of both to levels seen in heavy exercise produce a fall in resistance to near that observed during exercise. Since the enhanced vasodilator activity of venous blood from the contracting muscle was abolished by simultaneous correction of the PO2 and pH, it seems likely that these factors, acting directly or indirectly, are the principal chemicals responsible for the maintenance of the vasodilation seen in canine skeletal muscle during heavy exercise."}
{"id": "PMID:238406", "title": "Cardiac lymph flow and composition in acute myocardial ischemia in dogs.", "content": "Cardiac lymph was obtained from 12 normal dogs (group 1) for two consecutive 2-h control periods and from 7 dogs (group 2) for 2 h before and 2 h after occlusion of the circumflex branch of the left coronary artery. Lymph composition was studied with reference to pH, red blood cell (RBC) concentration, total protein content, potassium and sodium ion concentrations, and creatine phosphokinase (CPK) and acid phosphatase enzyme activities. No significant difference was noted in any variable between the two groups during the firts 2-h period. In group 1, no significant changes occurred in any variable as a result of the passage of time alone. In group 2, 2 h of myocardial ischemia produced increases of 53.3 plus or minus 5.1% in lymph flow, 67 plus or minus 5% in protein content, and 418 plus or minus 27% in the RBC concentration, suggesting increased blood capillary permeability. Lactate rose 120.5 plus or minus 27%, potassium concentration increased 16.9 plus or minus 2.4%, acid phosphatase increased 30 plus or minus 3%, and CPK rose 61.6 pluse or minus 10.9%, suggesting ischemic injury of myocardial cells. These changes in lymph were statistically significant (P LESS THAN 0.05) and reflect both capillary and myocardial cell abnormalities.", "contents": "Cardiac lymph flow and composition in acute myocardial ischemia in dogs. Cardiac lymph was obtained from 12 normal dogs (group 1) for two consecutive 2-h control periods and from 7 dogs (group 2) for 2 h before and 2 h after occlusion of the circumflex branch of the left coronary artery. Lymph composition was studied with reference to pH, red blood cell (RBC) concentration, total protein content, potassium and sodium ion concentrations, and creatine phosphokinase (CPK) and acid phosphatase enzyme activities. No significant difference was noted in any variable between the two groups during the firts 2-h period. In group 1, no significant changes occurred in any variable as a result of the passage of time alone. In group 2, 2 h of myocardial ischemia produced increases of 53.3 plus or minus 5.1% in lymph flow, 67 plus or minus 5% in protein content, and 418 plus or minus 27% in the RBC concentration, suggesting increased blood capillary permeability. Lactate rose 120.5 plus or minus 27%, potassium concentration increased 16.9 plus or minus 2.4%, acid phosphatase increased 30 plus or minus 3%, and CPK rose 61.6 pluse or minus 10.9%, suggesting ischemic injury of myocardial cells. These changes in lymph were statistically significant (P LESS THAN 0.05) and reflect both capillary and myocardial cell abnormalities."}
{"id": "PMID:238407", "title": "Catecholamine release: mechanism of mercury-induced vascular smooth muscle contraction.", "content": "The mechanism by which mercuric ion (HgCl2) induces contraction of vascular smooth muscle was defined in the kidney of anesthetized dogs and in rabbit aortic strips. In vivo, HgCl2 injected into the renal artery induced a dose-related reduction in renal blood flow (electromagnetic flowmeter) and glomerular filtration rate (creatinine clearance). An intra-arterial infusion of phenoxybenzamine (POB) significantly reduced the vascular response to HgCl2 (P less than 0.001). In vitro, alpha-adrenergic blockade with phentolamine and POB prevented mercury-induced contraction, whereas agents that block serotonin, histamine, acetylcholine, and angiotensin did not do so. Norepinephrine receptor \"protection\" from phenoxybenzamine blockade sustained the response to HgCl2. Reserpine pretreatment produced a parallel reduction in the response of the aorta to tyramine and mercury. The results are consistent with an indirect action of mercuric ion via release of endogenous catecholamines.", "contents": "Catecholamine release: mechanism of mercury-induced vascular smooth muscle contraction. The mechanism by which mercuric ion (HgCl2) induces contraction of vascular smooth muscle was defined in the kidney of anesthetized dogs and in rabbit aortic strips. In vivo, HgCl2 injected into the renal artery induced a dose-related reduction in renal blood flow (electromagnetic flowmeter) and glomerular filtration rate (creatinine clearance). An intra-arterial infusion of phenoxybenzamine (POB) significantly reduced the vascular response to HgCl2 (P less than 0.001). In vitro, alpha-adrenergic blockade with phentolamine and POB prevented mercury-induced contraction, whereas agents that block serotonin, histamine, acetylcholine, and angiotensin did not do so. Norepinephrine receptor \"protection\" from phenoxybenzamine blockade sustained the response to HgCl2. Reserpine pretreatment produced a parallel reduction in the response of the aorta to tyramine and mercury. The results are consistent with an indirect action of mercuric ion via release of endogenous catecholamines."}
{"id": "PMID:238408", "title": "Catecholamine effects on cyclic AMP levels and ion secretion in rabbit ileal mucosa.", "content": "Effects of catecholamines on cyclic AMP (cAMP) levels and ion fluxes were examined in isolated rabbit ileal mucosa. The base-line cAMP level was unaffected by epinephrine (Epi), norepinephrine (Norepi), and isoproterenol. The theophylline-augmented cAMP level was decreased slightly be Epi in one series of experiments but not in another. Propranolol did not enhance this effect. The increase in cAMP level produced by cholera toxin was almost completely reversed by addition of Epi or Norepi. This reversal was prevented by phenoxybenzamine. Epi also partially reversed the increase in cAMP level produced by prostaglandin E1. Effects of Epi on ion fluxes were determined following addition of secretagogues. Epi significantly decreased theophylline-induced but not cAMP or cholera toxin-induced Cl secretion. A decrease in short-circuit current was nonetheless observed in the latter two instances. The observed discrepancies between alpha-adrenergic effects on cAMP levels and ion fluxes suggest the following possibilities: 1) ion transport-related cAMP is only a small fraction of total mucosal cAMP; 2) cAMP-induced active ion secretion is only slowly reversible, or 3) effects of alpha-adrenergic stimuli on ion transport are not due to inhibition of cAMP accumulation.", "contents": "Catecholamine effects on cyclic AMP levels and ion secretion in rabbit ileal mucosa. Effects of catecholamines on cyclic AMP (cAMP) levels and ion fluxes were examined in isolated rabbit ileal mucosa. The base-line cAMP level was unaffected by epinephrine (Epi), norepinephrine (Norepi), and isoproterenol. The theophylline-augmented cAMP level was decreased slightly be Epi in one series of experiments but not in another. Propranolol did not enhance this effect. The increase in cAMP level produced by cholera toxin was almost completely reversed by addition of Epi or Norepi. This reversal was prevented by phenoxybenzamine. Epi also partially reversed the increase in cAMP level produced by prostaglandin E1. Effects of Epi on ion fluxes were determined following addition of secretagogues. Epi significantly decreased theophylline-induced but not cAMP or cholera toxin-induced Cl secretion. A decrease in short-circuit current was nonetheless observed in the latter two instances. The observed discrepancies between alpha-adrenergic effects on cAMP levels and ion fluxes suggest the following possibilities: 1) ion transport-related cAMP is only a small fraction of total mucosal cAMP; 2) cAMP-induced active ion secretion is only slowly reversible, or 3) effects of alpha-adrenergic stimuli on ion transport are not due to inhibition of cAMP accumulation."}
{"id": "PMID:238410", "title": "[Aqueous humor pH in experimental lye burns and influence of different treatment measures (author's transl)].", "content": "300 rabbit corneas were burned for 1 minute by applying a filter paper of 10 mm diameter soaked in different concentrations of NaOH. The aqueous humor pH was then measured at certain time intervals and after different treatment methods until the physiologic pH of 7.6 was reached. The results were statistically analysed. Group 1, 2 and 3 were burned in 1n NaOH, 3n NaOH, and 6n NaOH respectively without any treatment. In these groups a \"therapeutic\" pH-level of 8.5 was measured on an average 0.5, 2.5 and 5 hours after the burn (Table 1 and Fig. 2). Group 4 and 5 again were burned with 6n NaOH. In group 4 the burn was followed by constant irrigation with physiologic saline solution by means of the Morgan Therapeutic Lens (Fig. 1a and b). With this regimen a pH of 8.5 was reached after 2.5 hours (Table 1 and Fig. 3). In group 5 the physiologic saline solutions was replaced by a buffer solution (Isogutt) and a pH of 8.5 was measured after only one hour (Table 1 and Fig. 3). Based upon these results it is felt that severe lye burns should be treated by constant irrigation with a buffer solution for several hours. A treatment that can easily be performed by use of the Morgan Therapeutic Lens.", "contents": "[Aqueous humor pH in experimental lye burns and influence of different treatment measures (author's transl)]. 300 rabbit corneas were burned for 1 minute by applying a filter paper of 10 mm diameter soaked in different concentrations of NaOH. The aqueous humor pH was then measured at certain time intervals and after different treatment methods until the physiologic pH of 7.6 was reached. The results were statistically analysed. Group 1, 2 and 3 were burned in 1n NaOH, 3n NaOH, and 6n NaOH respectively without any treatment. In these groups a \"therapeutic\" pH-level of 8.5 was measured on an average 0.5, 2.5 and 5 hours after the burn (Table 1 and Fig. 2). Group 4 and 5 again were burned with 6n NaOH. In group 4 the burn was followed by constant irrigation with physiologic saline solution by means of the Morgan Therapeutic Lens (Fig. 1a and b). With this regimen a pH of 8.5 was reached after 2.5 hours (Table 1 and Fig. 3). In group 5 the physiologic saline solutions was replaced by a buffer solution (Isogutt) and a pH of 8.5 was measured after only one hour (Table 1 and Fig. 3). Based upon these results it is felt that severe lye burns should be treated by constant irrigation with a buffer solution for several hours. A treatment that can easily be performed by use of the Morgan Therapeutic Lens."}
{"id": "PMID:238411", "title": "Treatment of porcine malignant hyperthermia. A review based on experimental studies.", "content": "The metabolic and endocrine changes in porcine malignant hyperthermia are described and the importance of the catecholamine response emphasised. The relative effectiveness of several different therapeutic agents in the treatment of this syndrome in the Pietrain pig are described and the importance of a common link with the catecholamine response discussed.", "contents": "Treatment of porcine malignant hyperthermia. A review based on experimental studies. The metabolic and endocrine changes in porcine malignant hyperthermia are described and the importance of the catecholamine response emphasised. The relative effectiveness of several different therapeutic agents in the treatment of this syndrome in the Pietrain pig are described and the importance of a common link with the catecholamine response discussed."}
{"id": "PMID:238412", "title": "The neuromuscular blocking properties of AH 8165 during halothane anaesthesia.", "content": "The time to onset, duration, time for reversal, and dose required to abolish twitch response for AH 8165 have been investigated. The drug is shown to be a rapidly acting agent, with a duration of action similar to pancuronium.", "contents": "The neuromuscular blocking properties of AH 8165 during halothane anaesthesia. The time to onset, duration, time for reversal, and dose required to abolish twitch response for AH 8165 have been investigated. The drug is shown to be a rapidly acting agent, with a duration of action similar to pancuronium."}
{"id": "PMID:238413", "title": "Lorazepam as a premedicant for day-case surgery: an assessment.", "content": "The sedative effect of 2 mg of lorazepam was assessed in eleven patients undergoing minor \"day case\" surgery and the results compared with a control group of eleven patients receiving a placebo. Sedation was assessed by a scoring method and quantified in terms of change in plasma cortisol levels. The results indicate that 2 mg of oral lorazepam produces good sedation (superior to nitrazepam in terms of plasma cortisol reduction) and has a postoperative anti-emetic effect but its prolonged duration of action makes it unsuitable for patients returning home within 8 hours of premedication.", "contents": "Lorazepam as a premedicant for day-case surgery: an assessment. The sedative effect of 2 mg of lorazepam was assessed in eleven patients undergoing minor \"day case\" surgery and the results compared with a control group of eleven patients receiving a placebo. Sedation was assessed by a scoring method and quantified in terms of change in plasma cortisol levels. The results indicate that 2 mg of oral lorazepam produces good sedation (superior to nitrazepam in terms of plasma cortisol reduction) and has a postoperative anti-emetic effect but its prolonged duration of action makes it unsuitable for patients returning home within 8 hours of premedication."}
{"id": "PMID:238431", "title": "Anesthetic solubility coefficients for maternal and fetal blood.", "content": "Solubility coefficients for seven inhalation anesthetic agnets were determined in maternal and fetal blood at 37 C.  Halothane, isoflurane, diethyl ether, and nitrous oxide were significantly more soluble in maternal than in fetal blood, while methoxyflurane, fluroxene, and cyclopropane were significantly less soluble.  Reasons for these differences cannot be accounted for by differences in the type or amount of hemoglobin present.", "contents": "Anesthetic solubility coefficients for maternal and fetal blood. Solubility coefficients for seven inhalation anesthetic agnets were determined in maternal and fetal blood at 37 C.  Halothane, isoflurane, diethyl ether, and nitrous oxide were significantly more soluble in maternal than in fetal blood, while methoxyflurane, fluroxene, and cyclopropane were significantly less soluble.  Reasons for these differences cannot be accounted for by differences in the type or amount of hemoglobin present."}
{"id": "PMID:238429", "title": "Postoperative alveolar-arterial oxygen tension difference: its relation to the operative incision in obese patients.", "content": "Forty-eight markedly obese patients for elective jejunoileal bypass were studied during spontaneous ventilation preoperatively and then postoperatively after 2 to 4 hours and on each of days 1 to 5 to determine the effect of the operative incision (midline versus transverse) on the alveolar-arterial oxygen tension difference (A-aDO2). Compared with control (Pre-op.) A-aDO2, there was a significant increase in A-aDO2 in all patients, beginning in the postanesthetic recovery area and continuing through postoperative (P.O.) day 4. Comparing the mean increase in A-aDO2 (P.O.-Pre-op.) between the two incision groups, patients with a midline incision had a significantly greater (p smaller than 0.001) increase in A-aDO2 on control (Pre-op.) value by day 5. The authors conclude that in markedly obese subjects, the midline incision can be expected to result in both more profound and more prolonged reduction in arterial oxygenation postoperatively.", "contents": "Postoperative alveolar-arterial oxygen tension difference: its relation to the operative incision in obese patients. Forty-eight markedly obese patients for elective jejunoileal bypass were studied during spontaneous ventilation preoperatively and then postoperatively after 2 to 4 hours and on each of days 1 to 5 to determine the effect of the operative incision (midline versus transverse) on the alveolar-arterial oxygen tension difference (A-aDO2). Compared with control (Pre-op.) A-aDO2, there was a significant increase in A-aDO2 in all patients, beginning in the postanesthetic recovery area and continuing through postoperative (P.O.) day 4. Comparing the mean increase in A-aDO2 (P.O.-Pre-op.) between the two incision groups, patients with a midline incision had a significantly greater (p smaller than 0.001) increase in A-aDO2 on control (Pre-op.) value by day 5. The authors conclude that in markedly obese subjects, the midline incision can be expected to result in both more profound and more prolonged reduction in arterial oxygenation postoperatively."}
{"id": "PMID:238430", "title": "Effects of patient age, pH of cerebrospinal fluid, and vasopressors on onset and duration of spinal anesthesia.", "content": "Two hundred twenty-two spinal anesthesias were administered with 10 mg. of tetracaine and 1 ml. of 10 percent dextrose to investigate the effects of vasopressors, patients age, and pH of cerebrospinal fluid on the onset and duration of spinal anesthesia. Neither the differences in overall age, cerebrospinal fluid pH, nor the addition of vasopressors had any significant effect on onset. Duration, however, was significantly prolonged by the addition of vasopressors, 53 percent prolongation by 0.2 mg. of epinephrine and 72 percent prolongation by 2 mg. of phenylephrine.", "contents": "Effects of patient age, pH of cerebrospinal fluid, and vasopressors on onset and duration of spinal anesthesia. Two hundred twenty-two spinal anesthesias were administered with 10 mg. of tetracaine and 1 ml. of 10 percent dextrose to investigate the effects of vasopressors, patients age, and pH of cerebrospinal fluid on the onset and duration of spinal anesthesia. Neither the differences in overall age, cerebrospinal fluid pH, nor the addition of vasopressors had any significant effect on onset. Duration, however, was significantly prolonged by the addition of vasopressors, 53 percent prolongation by 0.2 mg. of epinephrine and 72 percent prolongation by 2 mg. of phenylephrine."}
{"id": "PMID:238434", "title": "Venomotor changes caused by halothane acting on the sympathetic nerves.", "content": "Experiments were performed to determine whether depression of venomotor responses with halothane results from interference with sympathetic activation or from an effect on venous smooth muscle cells.  Changes in isometric tension of isolated canine saphenous-vein strips were recorded.  Adrenergic activation was achieved by transmural electrical stimulation, by addition of tyramine, and by addition of morepinephrine.  Halothane (0.5 to 3 per cent) did not significantly alter basal tension.  It lessened the reaction of the veins to electrical stimulation but not their response to norepinephrine; it increased the response to tyramine.  Since the responses to norepinephrine and tyramine were not decreased, halothane appears to act on the nerve terminal to prevent release of neurotransmitter associated with nerve-terminal depolarization.  Thus, halothane causes inhibition of electrically induced venoconstriction in cutaneous veins, probably by interfering with the release of norepinephrine from nerve terminals rather than by an inhibitory effect on the smooth muscle cells.", "contents": "Venomotor changes caused by halothane acting on the sympathetic nerves. Experiments were performed to determine whether depression of venomotor responses with halothane results from interference with sympathetic activation or from an effect on venous smooth muscle cells.  Changes in isometric tension of isolated canine saphenous-vein strips were recorded.  Adrenergic activation was achieved by transmural electrical stimulation, by addition of tyramine, and by addition of morepinephrine.  Halothane (0.5 to 3 per cent) did not significantly alter basal tension.  It lessened the reaction of the veins to electrical stimulation but not their response to norepinephrine; it increased the response to tyramine.  Since the responses to norepinephrine and tyramine were not decreased, halothane appears to act on the nerve terminal to prevent release of neurotransmitter associated with nerve-terminal depolarization.  Thus, halothane causes inhibition of electrically induced venoconstriction in cutaneous veins, probably by interfering with the release of norepinephrine from nerve terminals rather than by an inhibitory effect on the smooth muscle cells."}
{"id": "PMID:238435", "title": "Systemic and regional blood-flow changes during spinal anesthesia in the rhesus monkey.", "content": "The radioactive microsphere technique was used to determine the distribution of cardiac output and regional blood flow in rhesus monkeys before and 10,20,40, and 80 minutes after induction of spinal anesthesia. Five monkeys were studied during low spinal anesthesia (sensory level T10) and five other monkeys were studied during high spinal anesthesia (sensory level T1). Each monkey served as its own control. There was no significant change in regional blood flow during T10 spinal anesthesia. During T1 spinal anesthesia, blood flow (per 100 g of tissue) to kidneys was significantly reduced at 20, 40, and 80 minutes, blood flows to liver and carcass were significantly reduced at 20 and 40 minutes and blood flows to miscellaneous organs (lymph nodes, salivary glands, etc.) were significantly reduced throughout anesthesia. Blood flows to heart, brain, and lower extremity during T1 spinal anesthesia showed only non-significant changes. Vascular resistance in the lower extremity was significantly reduced during both levels of spinal anesthesia, indicating arteriolar dilatation. Also, during both levels of anesthesia, the lungs received an increased proportion of the radioactive microspheres, suggesting increased peripheral arteriovenous shunting of microspheres due to the arteriolar dilatation.", "contents": "Systemic and regional blood-flow changes during spinal anesthesia in the rhesus monkey. The radioactive microsphere technique was used to determine the distribution of cardiac output and regional blood flow in rhesus monkeys before and 10,20,40, and 80 minutes after induction of spinal anesthesia. Five monkeys were studied during low spinal anesthesia (sensory level T10) and five other monkeys were studied during high spinal anesthesia (sensory level T1). Each monkey served as its own control. There was no significant change in regional blood flow during T10 spinal anesthesia. During T1 spinal anesthesia, blood flow (per 100 g of tissue) to kidneys was significantly reduced at 20, 40, and 80 minutes, blood flows to liver and carcass were significantly reduced at 20 and 40 minutes and blood flows to miscellaneous organs (lymph nodes, salivary glands, etc.) were significantly reduced throughout anesthesia. Blood flows to heart, brain, and lower extremity during T1 spinal anesthesia showed only non-significant changes. Vascular resistance in the lower extremity was significantly reduced during both levels of spinal anesthesia, indicating arteriolar dilatation. Also, during both levels of anesthesia, the lungs received an increased proportion of the radioactive microspheres, suggesting increased peripheral arteriovenous shunting of microspheres due to the arteriolar dilatation."}
{"id": "PMID:238436", "title": "Annals of allergy.", "content": "A review of the world literature regarding the relative efficacy, duration and toxicity of the available beta-adrenergic bronchodilator aerosols for the treatment of asthma is presented. Many of these agents will soon become available in the United States and some familiarity with their actions is necessary for optimal care of asthmatic patients.", "contents": "Annals of allergy. A review of the world literature regarding the relative efficacy, duration and toxicity of the available beta-adrenergic bronchodilator aerosols for the treatment of asthma is presented. Many of these agents will soon become available in the United States and some familiarity with their actions is necessary for optimal care of asthmatic patients."}
{"id": "PMID:238437", "title": "In vivo erythrocyte sickling in the Japanese sika deer (Cervus nippon): methodology.", "content": "The Japanese sika deep (Cervus nippon) proved to be a suitable animal model for the study of acute phases of in vivo erythrocyte sickling. Ophthalmologic studies can be conducted during or after 1 to 6 hours of effective in vivo sickling. Intravenous administration of 1.75 to 3.5% sodium bicarbonate solution at a rate of 500 to 1,000 ml per hour produced a transient state of alkalosis and in vivo erythrocyte sickling in the sika deer. The percentage of sickled erythrocytes increased as the blood pH increased. Concurrently, the packed cell volume decreased. Sickling was enhanced by 100% oxygen ventilation after endotracheal intubation and light anesthetization. After the induction of erythrocyte sickling, a sickling-reversal phenomenon occurred despite continued bicarbonate administration. During the course of this reversal, the percentage of sickled erythrocytes steadily decreased, the venous blood pH decreased, and the packed cell volume slowly increased. Because of the sickling-reversal phenomenon, chronic erythrocyte sickling was not achieved.", "contents": "In vivo erythrocyte sickling in the Japanese sika deer (Cervus nippon): methodology. The Japanese sika deep (Cervus nippon) proved to be a suitable animal model for the study of acute phases of in vivo erythrocyte sickling. Ophthalmologic studies can be conducted during or after 1 to 6 hours of effective in vivo sickling. Intravenous administration of 1.75 to 3.5% sodium bicarbonate solution at a rate of 500 to 1,000 ml per hour produced a transient state of alkalosis and in vivo erythrocyte sickling in the sika deer. The percentage of sickled erythrocytes increased as the blood pH increased. Concurrently, the packed cell volume decreased. Sickling was enhanced by 100% oxygen ventilation after endotracheal intubation and light anesthetization. After the induction of erythrocyte sickling, a sickling-reversal phenomenon occurred despite continued bicarbonate administration. During the course of this reversal, the percentage of sickled erythrocytes steadily decreased, the venous blood pH decreased, and the packed cell volume slowly increased. Because of the sickling-reversal phenomenon, chronic erythrocyte sickling was not achieved."}
{"id": "PMID:238438", "title": "Changes in motility and ph in the digestive tract of experimentally overfed sheep.", "content": "Motility of the digestive tract of 4 sheep was studied with radiotelemetric equipment. After base line records were made, each sheep was overfed with 70 g of grain per kilogram of body weight. The ruminoreticulum did not become static until the ingesta pH was less than 5. The cecum had the same patterns of motility and pH as did the ruminoreticulum, but these returned to normal more quickly in surviving sheep. The motility patterns of the abomasum and the small intestine were more erratic. Results indicated that considerable quantities of grain (substrate for microbial growth) reached the cecum before ruminoreticular motility was inhibited.", "contents": "Changes in motility and ph in the digestive tract of experimentally overfed sheep. Motility of the digestive tract of 4 sheep was studied with radiotelemetric equipment. After base line records were made, each sheep was overfed with 70 g of grain per kilogram of body weight. The ruminoreticulum did not become static until the ingesta pH was less than 5. The cecum had the same patterns of motility and pH as did the ruminoreticulum, but these returned to normal more quickly in surviving sheep. The motility patterns of the abomasum and the small intestine were more erratic. Results indicated that considerable quantities of grain (substrate for microbial growth) reached the cecum before ruminoreticular motility was inhibited."}
{"id": "PMID:238439", "title": "Physiologic studies of experimentally grain-engorged cattle and sheep.", "content": "Seven sheep weighing 34 to 41 kg, each, 3 steers and 1 heifer weighing 230 to 460 kg each, were experimentally, \"overfed\" (induced grain engorgement). The most significant changes occurred in ruminal ingesta pH, blood pH, packed cell volume (PCV), hemoglobin (Hb), carbon dioxide pressure (PCO2, total CO2 (volume %), blood D-lactic acid, blood HCO3, and base excess. There was no common denominator that was especially pathognomonic.", "contents": "Physiologic studies of experimentally grain-engorged cattle and sheep. Seven sheep weighing 34 to 41 kg, each, 3 steers and 1 heifer weighing 230 to 460 kg each, were experimentally, \"overfed\" (induced grain engorgement). The most significant changes occurred in ruminal ingesta pH, blood pH, packed cell volume (PCV), hemoglobin (Hb), carbon dioxide pressure (PCO2, total CO2 (volume %), blood D-lactic acid, blood HCO3, and base excess. There was no common denominator that was especially pathognomonic."}
{"id": "PMID:238440", "title": "Erythrocyte metabolism in normal and glutathione-deficient sheep.", "content": "Glucose utilization and lactate formation in erythrocytes from normal and glutathione (GSH)-deficient sheep were similar. Significant differences were observed, however, between the 2 groups of sheep in the production of 14-CO2 from erythrocytes incubated with ascorbic acid or methylene blue, or both. The greater response of normal erythrocytes compared to erythrocytes deficient in GSH suggests that there are some metabolic differences in the pentose phosphate pathway (ppp) activity of the erythrocytes. The nature and site of these differences are, however, not known. When sheep were kept in a decompression chamber for 2 weeks and subjected to a simulated altitude of 7,000 m for 12 hours/day, the erythrocytes showed a four- to six-fold increase in the activity of the ppp.", "contents": "Erythrocyte metabolism in normal and glutathione-deficient sheep. Glucose utilization and lactate formation in erythrocytes from normal and glutathione (GSH)-deficient sheep were similar. Significant differences were observed, however, between the 2 groups of sheep in the production of 14-CO2 from erythrocytes incubated with ascorbic acid or methylene blue, or both. The greater response of normal erythrocytes compared to erythrocytes deficient in GSH suggests that there are some metabolic differences in the pentose phosphate pathway (ppp) activity of the erythrocytes. The nature and site of these differences are, however, not known. When sheep were kept in a decompression chamber for 2 weeks and subjected to a simulated altitude of 7,000 m for 12 hours/day, the erythrocytes showed a four- to six-fold increase in the activity of the ppp."}
{"id": "PMID:238441", "title": "The detection of cross-reacting material for alpha-antitrypsin in liver extracts by acid-starch electrophoresis.", "content": "Purified extracts of alpha-antitrypsin cross-reacting material (CRM) from liver of patients with MM, ZZ, and MZ phenotypes were studied by acid-starch electrophoresis and crossed immunoelectrophoresis. It is believed that CRM-M from liver is derived primarily from postmortem digested serum antitrypsin, whereas CRM-Z is a product of postmortem digested antitrypsin from hepatocytes. All extracts produced small bands of antitrypsin on the cathodal side of the gel: A single M band migrated faster than the single Z band, whereas CRM from an MZ heterozygote produced a combination of 2 mobile bands. The CRM-Z (from a ZZ phenotype) did not migrate toward the anode, in contrast to the presence of a broad plateau of antitrypsin protein with CRM-M (from an MM phenotype) or CRM-MZ. Thus, most of the CRM-Z protein could not be accounted for on routine acid-starch electrophoresis. However, an anodal peak could be seen on starch gels with CRM-Z at less acidic pH, suggesting that the anodal-migrating CRM-Z protein is denatured and loses antigenicity at lower pH.", "contents": "The detection of cross-reacting material for alpha-antitrypsin in liver extracts by acid-starch electrophoresis. Purified extracts of alpha-antitrypsin cross-reacting material (CRM) from liver of patients with MM, ZZ, and MZ phenotypes were studied by acid-starch electrophoresis and crossed immunoelectrophoresis. It is believed that CRM-M from liver is derived primarily from postmortem digested serum antitrypsin, whereas CRM-Z is a product of postmortem digested antitrypsin from hepatocytes. All extracts produced small bands of antitrypsin on the cathodal side of the gel: A single M band migrated faster than the single Z band, whereas CRM from an MZ heterozygote produced a combination of 2 mobile bands. The CRM-Z (from a ZZ phenotype) did not migrate toward the anode, in contrast to the presence of a broad plateau of antitrypsin protein with CRM-M (from an MM phenotype) or CRM-MZ. Thus, most of the CRM-Z protein could not be accounted for on routine acid-starch electrophoresis. However, an anodal peak could be seen on starch gels with CRM-Z at less acidic pH, suggesting that the anodal-migrating CRM-Z protein is denatured and loses antigenicity at lower pH."}
{"id": "PMID:238443", "title": "Determinants of chronic obstructive pulmonary disease in patients with intermediate levels of alpha-antitrypsin.", "content": "We examined elderly heterozygotes for alpha-antitrypsin deficiency (phenotype MZ) to determine which of several factors might be associated with the development of chronic obstructive pulmonary disease (COPD). Elderly heterozygotes who smoked had a very high incidence of COPD (70 per cent), whereas homozygotes (phenotype MM) who smoked had a significantly lower incidence of COPD (35 per cent). There was no difference in the incidence of COPD between subjects with MM and MZ phenotypes who did not smoke. To determine if leukocyte enzymes were related to the development of COPD in elderly heterozygotes, we measured the activities of monocytic acid cathepsin, neutrophil acid cathepsin, neutral cathepsin, and elastase. The activities of these enzymes were not associated with the development of COPD or with smoking history in the heterozygotes. In conclusion, cigarette smoking seemed to be a significant determinant of the development of COPD in heterozygotes for alpha-antitrypsin deficiency, but the leukocyte enzyme actitivty that we studied was unrelated.", "contents": "Determinants of chronic obstructive pulmonary disease in patients with intermediate levels of alpha-antitrypsin. We examined elderly heterozygotes for alpha-antitrypsin deficiency (phenotype MZ) to determine which of several factors might be associated with the development of chronic obstructive pulmonary disease (COPD). Elderly heterozygotes who smoked had a very high incidence of COPD (70 per cent), whereas homozygotes (phenotype MM) who smoked had a significantly lower incidence of COPD (35 per cent). There was no difference in the incidence of COPD between subjects with MM and MZ phenotypes who did not smoke. To determine if leukocyte enzymes were related to the development of COPD in elderly heterozygotes, we measured the activities of monocytic acid cathepsin, neutrophil acid cathepsin, neutral cathepsin, and elastase. The activities of these enzymes were not associated with the development of COPD or with smoking history in the heterozygotes. In conclusion, cigarette smoking seemed to be a significant determinant of the development of COPD in heterozygotes for alpha-antitrypsin deficiency, but the leukocyte enzyme actitivty that we studied was unrelated."}
{"id": "PMID:238445", "title": "Flurazepam hydrochloride, a benzodiazepine hypnotic.", "content": "Flurazepam hydrochloride is a benzodiazepine derivative marketed for use as a hypnotic agent. Flurazepam is more effective than placebo and is as effective as other hypnotic drugs in most short-term controlled studies. In long-term dosage studies, flurazepam's efficacy persists while other hypnotics become ineffective. Flurazepam has relatively minor effects upon rapid eye movement (REM) sleep and does not lead to REM rebound; this may reduce the likelihood of drug dependence. Flurazepam does not cause enzyme induction and probably presents little hazard of abuse or overdosage. The rational use of hypnotic agents depends as much upon the underlying cause of the sleep disorder as upon the choice of a particular drug. When hypnotic therapy is indicated, flurazepam appears to have advantages over other drugs currently available in the United States.", "contents": "Flurazepam hydrochloride, a benzodiazepine hypnotic. Flurazepam hydrochloride is a benzodiazepine derivative marketed for use as a hypnotic agent. Flurazepam is more effective than placebo and is as effective as other hypnotic drugs in most short-term controlled studies. In long-term dosage studies, flurazepam's efficacy persists while other hypnotics become ineffective. Flurazepam has relatively minor effects upon rapid eye movement (REM) sleep and does not lead to REM rebound; this may reduce the likelihood of drug dependence. Flurazepam does not cause enzyme induction and probably presents little hazard of abuse or overdosage. The rational use of hypnotic agents depends as much upon the underlying cause of the sleep disorder as upon the choice of a particular drug. When hypnotic therapy is indicated, flurazepam appears to have advantages over other drugs currently available in the United States."}
{"id": "PMID:238446", "title": "Unanswered questions about the periodic health examination.", "content": "The periodic health examination in its application as a screening procedure in asymptomatic, ostensibly healthy persons is explored with a focus on the following issues: (a) the impact on health, (b) the content of a beneficial health examination, and (c) the effect of the examination on the physician-patient relation. The application discussed is distinct from use of the examination as a tool for diagnosis, prognosis, or therapeutic planning for patients with a specific illness. The discussion also shows a relatively recent change in the goal for the clinical assessment. There has been a shift in emphasis from establishing a diagnosis as the main outcome event of the periodic \"checkup\" to the identification of an intervention of value to the patient. Evidence from various studies that throw some light on related questions is considered. Special ethical issues surrounding the unsolicited medical assessment are identified. Finally, some ground rules for decisions about the periodic health examination are proposed.", "contents": "Unanswered questions about the periodic health examination. The periodic health examination in its application as a screening procedure in asymptomatic, ostensibly healthy persons is explored with a focus on the following issues: (a) the impact on health, (b) the content of a beneficial health examination, and (c) the effect of the examination on the physician-patient relation. The application discussed is distinct from use of the examination as a tool for diagnosis, prognosis, or therapeutic planning for patients with a specific illness. The discussion also shows a relatively recent change in the goal for the clinical assessment. There has been a shift in emphasis from establishing a diagnosis as the main outcome event of the periodic \"checkup\" to the identification of an intervention of value to the patient. Evidence from various studies that throw some light on related questions is considered. Special ethical issues surrounding the unsolicited medical assessment are identified. Finally, some ground rules for decisions about the periodic health examination are proposed."}
{"id": "PMID:238444", "title": "[Malabsorption of carbohydrates in children (author's transl)].", "content": "Physiological bases of digestion and absorption of carbohydrates are reviewed, as a preliminary step, in order to draw a general scheme of its patholophysiology. Clasification of different types of carbohydrate malabsorption is presented. Various exploration methods are discussed in terms of autors' own experiences. Relationship between a sugar screening test, faecal lactic acid contents and a simplified lactose tolerance test, is described in detail. Systematic diagnoses of these diseases are established. Different clinical pictures are reviewed. It is not yet well defined if a starch malabsorption can be caused by either a primary or secondary duodenal amylase deficiency. The clinical forms of congenital sucrose-isomaltose intolerance may be more attenuated than its classical form; incertain cases, secondary sucrose intolerance may also be present due to mucosa anatomic lesions. Maltose malabsorption has no clinical implications. As compared to other alpha-glycosidades, the trehalase activity has been not more affected by not using trehalose in feeding. Primary congenital lactase deficiency is not frequent, whereas secondary forms as much more usual and appear, in primary malabsorption syndromes and in the coeliac disease, very often along with clinical tolerance to lactose. In Spain, lactose nonabsorbers in 16.5% for adults 11.2% for adolescents and 18.3% for children, meaning, that it is being favored by environmental factors in the latter. The unspecified sugar malabsorption during the child's first year is still the most frequent cause of carbohydrate intolerance in children and, although certain progress has been achieved in its diagnosis and therapy, its pathogenic mechanism is not satisfactorily known yet.", "contents": "[Malabsorption of carbohydrates in children (author's transl)]. Physiological bases of digestion and absorption of carbohydrates are reviewed, as a preliminary step, in order to draw a general scheme of its patholophysiology. Clasification of different types of carbohydrate malabsorption is presented. Various exploration methods are discussed in terms of autors' own experiences. Relationship between a sugar screening test, faecal lactic acid contents and a simplified lactose tolerance test, is described in detail. Systematic diagnoses of these diseases are established. Different clinical pictures are reviewed. It is not yet well defined if a starch malabsorption can be caused by either a primary or secondary duodenal amylase deficiency. The clinical forms of congenital sucrose-isomaltose intolerance may be more attenuated than its classical form; incertain cases, secondary sucrose intolerance may also be present due to mucosa anatomic lesions. Maltose malabsorption has no clinical implications. As compared to other alpha-glycosidades, the trehalase activity has been not more affected by not using trehalose in feeding. Primary congenital lactase deficiency is not frequent, whereas secondary forms as much more usual and appear, in primary malabsorption syndromes and in the coeliac disease, very often along with clinical tolerance to lactose. In Spain, lactose nonabsorbers in 16.5% for adults 11.2% for adolescents and 18.3% for children, meaning, that it is being favored by environmental factors in the latter. The unspecified sugar malabsorption during the child's first year is still the most frequent cause of carbohydrate intolerance in children and, although certain progress has been achieved in its diagnosis and therapy, its pathogenic mechanism is not satisfactorily known yet."}
{"id": "PMID:238456", "title": "A military surgical team in Belfast.", "content": "This paper details the experiences of a military surgical team in Belfast from 1972 to early 1974. The overall picture of the problem is given and the current management of 'war' injuries discussed. Up to February 1974 over 1000 servicemen have been injured in Northern Ireland as a result of the vivil disturbance. Over 200 have died. Because of the close proximity of the hospital to many battle areas, casualties may arrive with massive injuries, requiring major resuscitation. Limb wounds have predominated. There is no short cut to adequate wound debridement, especially in the surgery of high-velocity missile injury. Missile wounds of the large bowel require a colostomy. Formal thoracotomy is increasingly used for the through-and-through gunshot wounds of the chest. Controlled ventilation is playing an increasingly important role in the management of some missile wounds of the head. Mine and bomb explosions frequently cause multiple injuries, requiring extensive surgery on any one patient.", "contents": "A military surgical team in Belfast. This paper details the experiences of a military surgical team in Belfast from 1972 to early 1974. The overall picture of the problem is given and the current management of 'war' injuries discussed. Up to February 1974 over 1000 servicemen have been injured in Northern Ireland as a result of the vivil disturbance. Over 200 have died. Because of the close proximity of the hospital to many battle areas, casualties may arrive with massive injuries, requiring major resuscitation. Limb wounds have predominated. There is no short cut to adequate wound debridement, especially in the surgery of high-velocity missile injury. Missile wounds of the large bowel require a colostomy. Formal thoracotomy is increasingly used for the through-and-through gunshot wounds of the chest. Controlled ventilation is playing an increasingly important role in the management of some missile wounds of the head. Mine and bomb explosions frequently cause multiple injuries, requiring extensive surgery on any one patient."}
{"id": "PMID:238457", "title": "Partial 4q trisomy. Apropos of 3 cases.", "content": "Three observations of partial trisomy 4q are reported: the first due to a familial translocation the second to a de nove translocation, the third to a \"mirror\" duplication. The very characteristic phenotype is compared to that of 4 other patients already reported in the literature. The most evocatory symptoms include: absent or poorly indicated nose bridge; pursed lips; shortness of the philtrum; and constant existence of a fold on the antitragus continuing the anthelix reachinghe insertion of the pinna.", "contents": "Partial 4q trisomy. Apropos of 3 cases. Three observations of partial trisomy 4q are reported: the first due to a familial translocation the second to a de nove translocation, the third to a \"mirror\" duplication. The very characteristic phenotype is compared to that of 4 other patients already reported in the literature. The most evocatory symptoms include: absent or poorly indicated nose bridge; pursed lips; shortness of the philtrum; and constant existence of a fold on the antitragus continuing the anthelix reachinghe insertion of the pinna."}
{"id": "PMID:238458", "title": "Hyperglycemia, polyol metabolism, and complications of diabetes mellitus.", "content": "This brief review of the sorbitol pathway has attempted to present our current knowledge of this accessory pathway of glucose metabolism in the development of some diabetic complications. Clearly hyperglycemia in the diabetic patient is an important factor controlling the activity of the sorbitol pathway. Hyperglycemia in both diabetic patients and experimental animals results in significant accumulations of the products of this pathway in some tissues, and these diabetic manifestations. The development of inhibitors of the aldose reductase enzyme affords new means for preventing and treating some of these complications. Nevertheless, we are still hampered by the lack of knowledge of the normal role of this pathway in tissue metabolism. Many technical problems still exist concerning sensitive and specific assays for the products of the sorbitol pathway in tissue studies, as well as with valid techniques for the measuremtn of the activity of this pathway in clinical situations. It is hoped that clinical studies with aldose reductase inhibitors in the future will further clarify the importance of this accesory pathway of glucose metabolism in diabetes.", "contents": "Hyperglycemia, polyol metabolism, and complications of diabetes mellitus. This brief review of the sorbitol pathway has attempted to present our current knowledge of this accessory pathway of glucose metabolism in the development of some diabetic complications. Clearly hyperglycemia in the diabetic patient is an important factor controlling the activity of the sorbitol pathway. Hyperglycemia in both diabetic patients and experimental animals results in significant accumulations of the products of this pathway in some tissues, and these diabetic manifestations. The development of inhibitors of the aldose reductase enzyme affords new means for preventing and treating some of these complications. Nevertheless, we are still hampered by the lack of knowledge of the normal role of this pathway in tissue metabolism. Many technical problems still exist concerning sensitive and specific assays for the products of the sorbitol pathway in tissue studies, as well as with valid techniques for the measuremtn of the activity of this pathway in clinical situations. It is hoped that clinical studies with aldose reductase inhibitors in the future will further clarify the importance of this accesory pathway of glucose metabolism in diabetes."}
{"id": "PMID:238461", "title": "Pharmacology of the esophageal motor funciton.", "content": "In the striated muscle of the upper esophageal sphincter, tonic maintenance of closure is probably mediated via tonic central excitation of the extrinsic motor innervation; relaxation represents central inhibition of this mechanism. The motor nerves are probably cholinergic and act through nicotinic receptors like those of somatic striated muscle. In the striated muscle of the esophageal body, swallowing-induced contraction is also probably a cholinergic and nicotinic response. In the smooth muscle of the esophageal body, the control of contractions is cholinergic and muscarinic in part, but there is evidence for a nonadrenergic and noncholinergic component as well. The muscarinic component may arise from the cholinergic innervation of the longitudinal muscle layer. The other component may lie in the cryptic innervation of the circular muscular layer. In the smooth-muscled lower esophageal sphincter, resting closure tension appears to reflect a variety of possible control mechanisms. No single control system predominates. The evidence for muscarinic excitation is equivocal. An excitatory adrenergic alpha mechanism and inhibitory adrenergic beta receptors may contribute. A role for the polypeptide hormones from the gastrointestinal tract seems unlikely. Relaxation of the lower sphincter with swallowing seems not to involve any of these mechanisms, but is apparently accomplished by nonadrenergic noncholinergic inhibitory nerves like those present elsewhere in the gut (87). The possibility that the transmitter of these nerves is an adenine nucleotide has been raised from studies of other parts of the gut, but that hypothesis has not yet been examined critically in the lower esophageal sphincter.", "contents": "Pharmacology of the esophageal motor funciton. In the striated muscle of the upper esophageal sphincter, tonic maintenance of closure is probably mediated via tonic central excitation of the extrinsic motor innervation; relaxation represents central inhibition of this mechanism. The motor nerves are probably cholinergic and act through nicotinic receptors like those of somatic striated muscle. In the striated muscle of the esophageal body, swallowing-induced contraction is also probably a cholinergic and nicotinic response. In the smooth muscle of the esophageal body, the control of contractions is cholinergic and muscarinic in part, but there is evidence for a nonadrenergic and noncholinergic component as well. The muscarinic component may arise from the cholinergic innervation of the longitudinal muscle layer. The other component may lie in the cryptic innervation of the circular muscular layer. In the smooth-muscled lower esophageal sphincter, resting closure tension appears to reflect a variety of possible control mechanisms. No single control system predominates. The evidence for muscarinic excitation is equivocal. An excitatory adrenergic alpha mechanism and inhibitory adrenergic beta receptors may contribute. A role for the polypeptide hormones from the gastrointestinal tract seems unlikely. Relaxation of the lower sphincter with swallowing seems not to involve any of these mechanisms, but is apparently accomplished by nonadrenergic noncholinergic inhibitory nerves like those present elsewhere in the gut (87). The possibility that the transmitter of these nerves is an adenine nucleotide has been raised from studies of other parts of the gut, but that hypothesis has not yet been examined critically in the lower esophageal sphincter."}
{"id": "PMID:238462", "title": "In vitro models in the study of structure-activity relationships of narcotic analgesics.", "content": "Evidence has been adduced for the view that the morphiness receptor or receptors in the myenteric plexus of guinea pig ileum are very similar to the brain receptors that mediate the analgesic action of the narcotic alagesics.  Such an in vitro model is very suitable for the study of structure-activity relationships because the angonist and antagonist activities of compounds can readily be assessed. One example is the investigation of the effects of changes at the N atom. Another point of interest is the role of substitutions at the C14 atom in morphine and morphinans. Such alterations in structure may have a profound effect on the relative agonist and antagonist activities and may convert a drug with dual agonist and antagonist actions into an antagonist devoid of agonist action.", "contents": "In vitro models in the study of structure-activity relationships of narcotic analgesics. Evidence has been adduced for the view that the morphiness receptor or receptors in the myenteric plexus of guinea pig ileum are very similar to the brain receptors that mediate the analgesic action of the narcotic alagesics.  Such an in vitro model is very suitable for the study of structure-activity relationships because the angonist and antagonist activities of compounds can readily be assessed. One example is the investigation of the effects of changes at the N atom. Another point of interest is the role of substitutions at the C14 atom in morphine and morphinans. Such alterations in structure may have a profound effect on the relative agonist and antagonist activities and may convert a drug with dual agonist and antagonist actions into an antagonist devoid of agonist action."}
{"id": "PMID:238465", "title": "Effect of pH and human serum on the susceptibility of group D streptococci (Enterococci) to ampicillin in vitro.", "content": "The in vitro susceptibility of group D streptococci (enterococci) to ampicillin was studied comparing the results obtained in Mueller-Hinton broth (MHB) with those obtained in normal human serum (NHS). The rate of enterococcal killing was consistently faster in NHS than in MHB at equivalent ampicillin concentrations. Whereas an increasing media pH appeared to decrease the susceptibility of enterococci to ampicillin by determinations of the minimum bactericidal concentration (MBC) of ampicillin, an opposite increase in susceptibility was observed when the rate of bactericidal activity was studied. This difference may be explainable by the instability of ampicillin at higher pH values. In both MHB and NHS a paradoxical decrease in the rate and extent of enterococcal killing occurred as the ampicillin concentration was increased above the minimally effective concentration. These results demonstrate the inadequacies of the MBC test system and the need for standardizing test media used for determining the susceptibility of enterococci to ampicillin.", "contents": "Effect of pH and human serum on the susceptibility of group D streptococci (Enterococci) to ampicillin in vitro. The in vitro susceptibility of group D streptococci (enterococci) to ampicillin was studied comparing the results obtained in Mueller-Hinton broth (MHB) with those obtained in normal human serum (NHS). The rate of enterococcal killing was consistently faster in NHS than in MHB at equivalent ampicillin concentrations. Whereas an increasing media pH appeared to decrease the susceptibility of enterococci to ampicillin by determinations of the minimum bactericidal concentration (MBC) of ampicillin, an opposite increase in susceptibility was observed when the rate of bactericidal activity was studied. This difference may be explainable by the instability of ampicillin at higher pH values. In both MHB and NHS a paradoxical decrease in the rate and extent of enterococcal killing occurred as the ampicillin concentration was increased above the minimally effective concentration. These results demonstrate the inadequacies of the MBC test system and the need for standardizing test media used for determining the susceptibility of enterococci to ampicillin."}
{"id": "PMID:238466", "title": "Inhibition of pathogenic enteric bacteria by hyperbaric oxygen: enhanced antibacterial activity in the absence of carbon dioxide.", "content": "The antibacterial effects of 24-h exposures to high-pressure oxygen in relation to environmental CO(2) were studied at 3 atm absolute (ata) and at 1 ata. Eight gram-negative, aerobic and facultatively aerobic, pathogenic enteric bacteria (Salmonella typhosa, Salmonella paratyphi, Salmonella schottmuelleri, Shigella dysenteriae, Shigella flexneri, Proteus vulgaris, Pseudomonas aeruginosa, and Escherichia coli) were exposed as shallow-broth cultures and agar surface cultures. Although broths supplemented with 0.2% glucose permitted some growth of Salmonella typhosa, Salmonella schottmuelleri, Shigella dysenteriae, and Shigella flexneri during exposure to high-pressure oxygen in the presence of CO(2), the other species grew only after the exposure, indicating a bacteriostatic effect. Both bacteriostatic and bactericidal effects were demonstrated on the surface of Trypticase soy agar, where killing of Salmonellea typhosa, Proteus vulgaris, and Pseudomonas aeruginosa was significantly greater after exposure to pure O(2) at 3 ata than at 1 ata. At 3 ata, significantly more killing occurred upon exposure of all species (except Shigella dysenteriae and S. flexneri) on an agar surface to 100% O(2) as compared with exposure to a mixture of 95% O(2) + 5% CO(2). Thus, deprivation of CO(2) during exposure to pure O(2) enhanced the bactericidal effect of high-pressure oxygen.", "contents": "Inhibition of pathogenic enteric bacteria by hyperbaric oxygen: enhanced antibacterial activity in the absence of carbon dioxide. The antibacterial effects of 24-h exposures to high-pressure oxygen in relation to environmental CO(2) were studied at 3 atm absolute (ata) and at 1 ata. Eight gram-negative, aerobic and facultatively aerobic, pathogenic enteric bacteria (Salmonella typhosa, Salmonella paratyphi, Salmonella schottmuelleri, Shigella dysenteriae, Shigella flexneri, Proteus vulgaris, Pseudomonas aeruginosa, and Escherichia coli) were exposed as shallow-broth cultures and agar surface cultures. Although broths supplemented with 0.2% glucose permitted some growth of Salmonella typhosa, Salmonella schottmuelleri, Shigella dysenteriae, and Shigella flexneri during exposure to high-pressure oxygen in the presence of CO(2), the other species grew only after the exposure, indicating a bacteriostatic effect. Both bacteriostatic and bactericidal effects were demonstrated on the surface of Trypticase soy agar, where killing of Salmonellea typhosa, Proteus vulgaris, and Pseudomonas aeruginosa was significantly greater after exposure to pure O(2) at 3 ata than at 1 ata. At 3 ata, significantly more killing occurred upon exposure of all species (except Shigella dysenteriae and S. flexneri) on an agar surface to 100% O(2) as compared with exposure to a mixture of 95% O(2) + 5% CO(2). Thus, deprivation of CO(2) during exposure to pure O(2) enhanced the bactericidal effect of high-pressure oxygen."}
{"id": "PMID:238467", "title": "Inactivation of enterovirus by glutaraldehyde.", "content": "A study on the rate of inactivation by glutaraldehyde of coxsackievirus was conducted using different concentrations, temperatures, and pH values. It was found, that 2 percent glutaraldehyde at pH 7.4 and 25 C, as recommended for a sporicide, reduced the titer of infectious virus by 2 log10U in 1 min or less. The reduction was not negatively affected by high concentrations of organic matter (serum and animal spillings) in the reaction mixtures.", "contents": "Inactivation of enterovirus by glutaraldehyde. A study on the rate of inactivation by glutaraldehyde of coxsackievirus was conducted using different concentrations, temperatures, and pH values. It was found, that 2 percent glutaraldehyde at pH 7.4 and 25 C, as recommended for a sporicide, reduced the titer of infectious virus by 2 log10U in 1 min or less. The reduction was not negatively affected by high concentrations of organic matter (serum and animal spillings) in the reaction mixtures."}
{"id": "PMID:238468", "title": "Common mesophilic anaerobes, including Clostridium botulinum and Clostridium tetani, in 21 soil specimens.", "content": "A relatively rich medium was markedly superior to a dilute medium for the isolation of anaerobic bacteria from soil. The obligate anaerobes isolated from 21 soil samples were all clostridia and the counts ranged from 2.7 X 10-2 to 3.3 X 10-6 per g. The organisms most frequently isolated were Clostridium subterminate, C. sordelii, C. sporogenes, C. indolis, C. bifermentans, C. mangenoti, and C. perfringens. Seventeen other species were also recognized but almost one-third of the isolates could not be identified with any known species of Clostridium. C. botulinum type A was demonstrated in six soil samples, and type B in one. These soils were neutral to alkaline in reaction (average pH 7.9) and low in organic matter content (1.4%). The association of C. botulinum types A and B with neutral to alkaline soils was statistically significant (P = 0.001) as was their association with soils low in organic matter (P = 0.005). C. botulinum types E and F were found in one soil sample, pH 4.5, with organic matter 13.7%. C. tetani was isolated from two soil samples, both of intermediate pH value and higher than average organic matter content.", "contents": "Common mesophilic anaerobes, including Clostridium botulinum and Clostridium tetani, in 21 soil specimens. A relatively rich medium was markedly superior to a dilute medium for the isolation of anaerobic bacteria from soil. The obligate anaerobes isolated from 21 soil samples were all clostridia and the counts ranged from 2.7 X 10-2 to 3.3 X 10-6 per g. The organisms most frequently isolated were Clostridium subterminate, C. sordelii, C. sporogenes, C. indolis, C. bifermentans, C. mangenoti, and C. perfringens. Seventeen other species were also recognized but almost one-third of the isolates could not be identified with any known species of Clostridium. C. botulinum type A was demonstrated in six soil samples, and type B in one. These soils were neutral to alkaline in reaction (average pH 7.9) and low in organic matter content (1.4%). The association of C. botulinum types A and B with neutral to alkaline soils was statistically significant (P = 0.001) as was their association with soils low in organic matter (P = 0.005). C. botulinum types E and F were found in one soil sample, pH 4.5, with organic matter 13.7%. C. tetani was isolated from two soil samples, both of intermediate pH value and higher than average organic matter content."}
{"id": "PMID:238469", "title": "Extracellular lipids of Cladosporium (Amorphotheca) resinae grown on glucose or on n-alkanes.", "content": "Cladosporium (Amorphotheca) resinae was grown in shake culture on glucose, n-dodecane, or n-hexadecane. Growth was most rapid on glucose, and more acid accumulated in the medium than in n-alkane-grown cultures. Neutral lipid was the major lipid fraction and triglycerides were the only extracellular neutral lipids detected. Dodecanoic (lauir) acid was the predominant fatty acid (greater than 60%) in neutral lipids from all three media, with lesser amounts of tetradecanoic, hexadecanoic, and octadecanoic acids. Extracellular phospholipids identified were phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine, and cardiolipin or a cardiolipin-like compound. Phospholipids from all three media contained dodecanoic acid as their principle fatty acid. Dodecanoic acid was the only extracellular free fatty acid detected. Glucose medium contained acetic, glyoxylic, and glycolic acids and an unidentified organic acid which may contribute to the lower pH in cultures after growth on glucose. In all classes of extracellular lipids the fatty acids do not correspond to the fatty acids previously determined to be associated with cellular lipids. Moreover, the fatty acids of extracellular lipids do not reflect the chain length of the n-alkane growth substrate.", "contents": "Extracellular lipids of Cladosporium (Amorphotheca) resinae grown on glucose or on n-alkanes. Cladosporium (Amorphotheca) resinae was grown in shake culture on glucose, n-dodecane, or n-hexadecane. Growth was most rapid on glucose, and more acid accumulated in the medium than in n-alkane-grown cultures. Neutral lipid was the major lipid fraction and triglycerides were the only extracellular neutral lipids detected. Dodecanoic (lauir) acid was the predominant fatty acid (greater than 60%) in neutral lipids from all three media, with lesser amounts of tetradecanoic, hexadecanoic, and octadecanoic acids. Extracellular phospholipids identified were phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine, and cardiolipin or a cardiolipin-like compound. Phospholipids from all three media contained dodecanoic acid as their principle fatty acid. Dodecanoic acid was the only extracellular free fatty acid detected. Glucose medium contained acetic, glyoxylic, and glycolic acids and an unidentified organic acid which may contribute to the lower pH in cultures after growth on glucose. In all classes of extracellular lipids the fatty acids do not correspond to the fatty acids previously determined to be associated with cellular lipids. Moreover, the fatty acids of extracellular lipids do not reflect the chain length of the n-alkane growth substrate."}
{"id": "PMID:238470", "title": "Effect of pH on sporulation of Bacillus stearothermophilus.", "content": "An improved broth medium was developed for high growth yields of Bacillus subtilis var. niger NCIB 8649, Bacillus cereus NCIB 9373, and Bacillus stearothermophilus NCIB 8919 and ATCC 7953. Sporulation was abundant (1.1 times 10-8 B. subtilis var. niger and 9.2 times 10-7 B. cereus per ml) at an initial pH of 7.0. Sporulation of both strains of B. stearothermophilus took place (1.9 times 10-7 and 2.4 times 10-7/ml, respectively) in this medium when initial pH values of 7.7 to 8.7 were used.", "contents": "Effect of pH on sporulation of Bacillus stearothermophilus. An improved broth medium was developed for high growth yields of Bacillus subtilis var. niger NCIB 8649, Bacillus cereus NCIB 9373, and Bacillus stearothermophilus NCIB 8919 and ATCC 7953. Sporulation was abundant (1.1 times 10-8 B. subtilis var. niger and 9.2 times 10-7 B. cereus per ml) at an initial pH of 7.0. Sporulation of both strains of B. stearothermophilus took place (1.9 times 10-7 and 2.4 times 10-7/ml, respectively) in this medium when initial pH values of 7.7 to 8.7 were used."}
{"id": "PMID:238471", "title": "Effects of trace metals on the production of aflatoxins by Aspergillus parasiticus.", "content": "Certain metals added as salts to a defined basal culture medium influenced the level of aflatoxin production by Aspergillus parasiticus in the low micrograms-per-milliliter range of the added metal. In many cases no change or a relatively small change in mat weight and final pH of the medium accompanied this effect. With zinc at added levels of 0 to 10 mug/ml in the medium, aflatoxin increased 30-to 1,000-fold with increasing of zinc, whereas mat weight increased less than threefold. At 25 mug of added zinc per ml, aflatoxin decreased, but mat weight did not. At an added level of 25 mug or less of the metal per ml, salts of iron, manganese, cooper, cadmium, trivalent chromium, silver, and mercury partly or completelyinhibited aflatoxin production, without influencing mat weight.", "contents": "Effects of trace metals on the production of aflatoxins by Aspergillus parasiticus. Certain metals added as salts to a defined basal culture medium influenced the level of aflatoxin production by Aspergillus parasiticus in the low micrograms-per-milliliter range of the added metal. In many cases no change or a relatively small change in mat weight and final pH of the medium accompanied this effect. With zinc at added levels of 0 to 10 mug/ml in the medium, aflatoxin increased 30-to 1,000-fold with increasing of zinc, whereas mat weight increased less than threefold. At 25 mug of added zinc per ml, aflatoxin decreased, but mat weight did not. At an added level of 25 mug or less of the metal per ml, salts of iron, manganese, cooper, cadmium, trivalent chromium, silver, and mercury partly or completelyinhibited aflatoxin production, without influencing mat weight."}
{"id": "PMID:238472", "title": "Metabolism of deoxycorticosterone by human fecal flora.", "content": "21-Dehydroxylation, a feature of metabolism of corticoids in humans, was observed in mixed cultures of fecal flora of normal individuals on a Western diet. The model substrate, 11-deoxycorticosterone (DOC), was metabolized to 3alpha-21-dihydroxy-5beta-pregnan-20-one (THDOC), 3alpha-hydroxy-5beta-pregnan20-one (pregnanolone), and to two unidentified structures, metabolites X and Y. DOC was not metabolized in all media supporting growth of fecal flora. Conversion required an initial pH between 6.0 and 8.0. 21-Dehydroxylation occurred within 4 days of incubation in media inoculated with 10-minus 1 to 10-minus 7 fecal suspensions. In higher dilutions, containing obligatory anaerobes only, DOC was converted to metabolite X and sometimes also to metabolite Y. The yield of pregnanolone was related to the promptness with which the specimen was processed, to the presence of cysteine in the medium, and to the concentrationof substrate (optimum, 16 to 64 mug of DOC per ml). The yield of THDOC was related to the delay in the processing of the specimen, the concentration of substrate (maximum at 256 mug/ml), and aeration of the culture. Pure cultures of aerobic organism of fecal origin either failed to metabolize DOC or converted it to metabolite Y. Pure cultures of fecal anaerobes converted DOC to metabolite X and sometimes also to metabolite Y. Neither THDOC nor pregnanolone was produced by pure cultures.", "contents": "Metabolism of deoxycorticosterone by human fecal flora. 21-Dehydroxylation, a feature of metabolism of corticoids in humans, was observed in mixed cultures of fecal flora of normal individuals on a Western diet. The model substrate, 11-deoxycorticosterone (DOC), was metabolized to 3alpha-21-dihydroxy-5beta-pregnan-20-one (THDOC), 3alpha-hydroxy-5beta-pregnan20-one (pregnanolone), and to two unidentified structures, metabolites X and Y. DOC was not metabolized in all media supporting growth of fecal flora. Conversion required an initial pH between 6.0 and 8.0. 21-Dehydroxylation occurred within 4 days of incubation in media inoculated with 10-minus 1 to 10-minus 7 fecal suspensions. In higher dilutions, containing obligatory anaerobes only, DOC was converted to metabolite X and sometimes also to metabolite Y. The yield of pregnanolone was related to the promptness with which the specimen was processed, to the presence of cysteine in the medium, and to the concentrationof substrate (optimum, 16 to 64 mug of DOC per ml). The yield of THDOC was related to the delay in the processing of the specimen, the concentration of substrate (maximum at 256 mug/ml), and aeration of the culture. Pure cultures of aerobic organism of fecal origin either failed to metabolize DOC or converted it to metabolite Y. Pure cultures of fecal anaerobes converted DOC to metabolite X and sometimes also to metabolite Y. Neither THDOC nor pregnanolone was produced by pure cultures."}
{"id": "PMID:238473", "title": "Necrotizing vasculitis. Etiologic aspects of immunology and coagulopathy.", "content": "Thirty-one patients with cutaneous necrotizing vascultis were studied for immunological and coagulation disturbances. Serum immunoglobulin levels did not correlate with tissue deposition of the corresponding immunoglobulins in the lesions of cutaneous necrotizing vasculitis. In all instances, localization of immunoglobulins, complement, and fibrinogen, when present in the lesions of necrotizing vasculitis, was limited to the vascular wall or perivascular space. Soluble fibrinogen-fibrin complexes (cryoprofibrin) were detected in the blood of four of 17 patients with cutaneous necrotizing vasculitis. Since it represents a product of the limited action of thrombin on fibrinogen, its presence in the blood in some patients with necrotizing vasculitis suggests that intravascular coagulation may play a part in the pathogenesis of the disease. In 12 of the 31 patients studied, a cause of the vasculitis was found or presumed.", "contents": "Necrotizing vasculitis. Etiologic aspects of immunology and coagulopathy. Thirty-one patients with cutaneous necrotizing vascultis were studied for immunological and coagulation disturbances. Serum immunoglobulin levels did not correlate with tissue deposition of the corresponding immunoglobulins in the lesions of cutaneous necrotizing vasculitis. In all instances, localization of immunoglobulins, complement, and fibrinogen, when present in the lesions of necrotizing vasculitis, was limited to the vascular wall or perivascular space. Soluble fibrinogen-fibrin complexes (cryoprofibrin) were detected in the blood of four of 17 patients with cutaneous necrotizing vasculitis. Since it represents a product of the limited action of thrombin on fibrinogen, its presence in the blood in some patients with necrotizing vasculitis suggests that intravascular coagulation may play a part in the pathogenesis of the disease. In 12 of the 31 patients studied, a cause of the vasculitis was found or presumed."}
{"id": "PMID:238474", "title": "Familial glucocorticoid deficiency. Studies of diagnosis and pathogenesis.", "content": "The clinical and biochemical findings are described in 2 brothers who had intermittent hypoglycaemia generally precipitated by the \"stress\" of infection. Both were tall and pigmented. Both boys showed a failure of adrenocortical response to ACTH which was progressive in the eldest boy. The diagnosis of familial glucocorticoid deficiency (hereditary adrenocortical unresponsiveness) was confirmed by the absence of electrolyte imbalance even on a low sodium diet, and by very high levels of ACTH in plasma. High levels of deoxycorticosterone (DOC) were found in both children with normal levels of other plasma corticosteroids. It is suggested that the high levels of DOC may be in some way related to the apparent persistence of a \"fetal\" type of adrenocortical steroid biosynthesis for 18 months or more in these boys. After the diagnosis, established by relatively simple methods, treatment with cortisone acetate has 0een highly effective.", "contents": "Familial glucocorticoid deficiency. Studies of diagnosis and pathogenesis. The clinical and biochemical findings are described in 2 brothers who had intermittent hypoglycaemia generally precipitated by the \"stress\" of infection. Both were tall and pigmented. Both boys showed a failure of adrenocortical response to ACTH which was progressive in the eldest boy. The diagnosis of familial glucocorticoid deficiency (hereditary adrenocortical unresponsiveness) was confirmed by the absence of electrolyte imbalance even on a low sodium diet, and by very high levels of ACTH in plasma. High levels of deoxycorticosterone (DOC) were found in both children with normal levels of other plasma corticosteroids. It is suggested that the high levels of DOC may be in some way related to the apparent persistence of a \"fetal\" type of adrenocortical steroid biosynthesis for 18 months or more in these boys. After the diagnosis, established by relatively simple methods, treatment with cortisone acetate has 0een highly effective."}
{"id": "PMID:238476", "title": "Plasma gastrin in congenitial hypertrophic pyloric stenosis. A hypothesis disproved.", "content": "Fasting plasma gastrin levels were measured in babies with pyloric stenosis and in normal babies of similar age. There was no difference in gastrin levels either before or after operation between the babies with pyloric stenosis and normal babies. Similarly, neither the fasting blood glucose nor the fasting gastric pH of the babies with pyloric stenosis differed significantly from the values obtained in normal babies. Our findings do not support the hypothesis that gastrin in the fasting baby has an aetiological role in the development of hypertrophic pyloric stenosis of infancy. An alternative hypothesis is suggested.", "contents": "Plasma gastrin in congenitial hypertrophic pyloric stenosis. A hypothesis disproved. Fasting plasma gastrin levels were measured in babies with pyloric stenosis and in normal babies of similar age. There was no difference in gastrin levels either before or after operation between the babies with pyloric stenosis and normal babies. Similarly, neither the fasting blood glucose nor the fasting gastric pH of the babies with pyloric stenosis differed significantly from the values obtained in normal babies. Our findings do not support the hypothesis that gastrin in the fasting baby has an aetiological role in the development of hypertrophic pyloric stenosis of infancy. An alternative hypothesis is suggested."}
{"id": "PMID:238477", "title": "Separation and molecular weight estimation of phosphatases in psoriatic scales by disc-electrophoresis.", "content": "Disc-electrophoretic investigations of psoriatic scale homogenates (15000 x g supernatant) revealed several different phosphatase activities. At pH 5 either five different phosphatase active bands (substrates: p-nitrophenylphosphate, naphthylphosphate) or three different bands (substrate: glycerophosphate) could be obtained. At pH 7 only one band (substrate: p-nitrophenylphosphate) showed phosphatase activity. At pH 9.9 either two bands (substrate: p-nitrophenylphosphate) or three bands (substrate: glycerophosphate) could be demonstrated. the acid p-nitrophenylphosphatase activity of the psoriatic specific bands \"9\" and \"10\" could be distinguished by their different fluoride and tartrate susceptibility. Also the alkaline glycerophosphatase activities could be differentiated by distinct Ca and Mg susceptibility.", "contents": "Separation and molecular weight estimation of phosphatases in psoriatic scales by disc-electrophoresis. Disc-electrophoretic investigations of psoriatic scale homogenates (15000 x g supernatant) revealed several different phosphatase activities. At pH 5 either five different phosphatase active bands (substrates: p-nitrophenylphosphate, naphthylphosphate) or three different bands (substrate: glycerophosphate) could be obtained. At pH 7 only one band (substrate: p-nitrophenylphosphate) showed phosphatase activity. At pH 9.9 either two bands (substrate: p-nitrophenylphosphate) or three bands (substrate: glycerophosphate) could be demonstrated. the acid p-nitrophenylphosphatase activity of the psoriatic specific bands \"9\" and \"10\" could be distinguished by their different fluoride and tartrate susceptibility. Also the alkaline glycerophosphatase activities could be differentiated by distinct Ca and Mg susceptibility."}
{"id": "PMID:238478", "title": "Abolition of reactive hyperemia in the dog heart following alpha adrenergic blockade and its reversal by vasopressin.", "content": "The local intracoronary application of the alpha adrenergic blocking agents phenoxybenzamine or dibenamine, in open chest anesthetized dogs, regularly resulted in maximal coronary vasodilatation thus abolishing reactive hyperemia. Infusion of vasopression or angiotensin returned coronary flow to near control levels and restored reactive hyperemia. It is thus concluded that although alpha blocking agents can relax coronary vessel smooth muscle, reactive hyperemia does not appear to be mediated through the inhibition of alpha adrenergic constrictor tone.", "contents": "Abolition of reactive hyperemia in the dog heart following alpha adrenergic blockade and its reversal by vasopressin. The local intracoronary application of the alpha adrenergic blocking agents phenoxybenzamine or dibenamine, in open chest anesthetized dogs, regularly resulted in maximal coronary vasodilatation thus abolishing reactive hyperemia. Infusion of vasopression or angiotensin returned coronary flow to near control levels and restored reactive hyperemia. It is thus concluded that although alpha blocking agents can relax coronary vessel smooth muscle, reactive hyperemia does not appear to be mediated through the inhibition of alpha adrenergic constrictor tone."}
{"id": "PMID:238479", "title": "Timolol maleate, a new beta-adrenergic receptor blocking agent.", "content": "Some pharmacodynamic properties of an oxypropanolamine substituted novel heterocyclic compound are described. Initial studies involve comparison of the racemic mixture, dl-timolol maleate, with the beta-adrenergic receptor blocking agent propranolol in the rat, dog and cat. dl-Timolol maleate is shown to be a potent inhibitor of cardiovascular beta-adrenergic receptors activated by isoproterenol or adrenergic nerve stimulation. Blockade of alpha-adrenergic receptors is not observed even after extremely high doses. The compound is approximately 3 times more potent than propranolol in suppressing isoproterenol-induced cardioacceleration by the i.v. route of administration. dl-Timolol maleate is also extremely well absorbed when given orally, being then about 10 times more active than propranolol. Unlike propranolol, neither dl-timolol maleate nor its optical isomers possess demonstrable local anesthetic activity. Similar to propranolol and other beta-adrenergic receptor blocking agents, activity of the compound resides predominantly in the l-isomer (timolol maleate.", "contents": "Timolol maleate, a new beta-adrenergic receptor blocking agent. Some pharmacodynamic properties of an oxypropanolamine substituted novel heterocyclic compound are described. Initial studies involve comparison of the racemic mixture, dl-timolol maleate, with the beta-adrenergic receptor blocking agent propranolol in the rat, dog and cat. dl-Timolol maleate is shown to be a potent inhibitor of cardiovascular beta-adrenergic receptors activated by isoproterenol or adrenergic nerve stimulation. Blockade of alpha-adrenergic receptors is not observed even after extremely high doses. The compound is approximately 3 times more potent than propranolol in suppressing isoproterenol-induced cardioacceleration by the i.v. route of administration. dl-Timolol maleate is also extremely well absorbed when given orally, being then about 10 times more active than propranolol. Unlike propranolol, neither dl-timolol maleate nor its optical isomers possess demonstrable local anesthetic activity. Similar to propranolol and other beta-adrenergic receptor blocking agents, activity of the compound resides predominantly in the l-isomer (timolol maleate."}
{"id": "PMID:238480", "title": "Predictive value of various parameters for the antihypertensive effect of the beta blocker ICI 66,082 (1).", "content": "The antihypertensive effect of the new beta-blocker, ICI 66,082 was studied in 37 patients with renal or essential hypertension. A daily dose of 75 mg produced a significant antihypertensive effect and a further blood pressure decrease was obtained by increasing the daily dose up to 300 mg; at this treatment level, the antihypertensive effect averaged 29.4/24.0 mm Hg. Increasing the dose from 300 to 600 mg daily did not produce a significant additional blood pressure decrease. Six of the 37 patients retained fluid, producing a loss in the antihypertensive effect. No significant correlation was found between the percentage systolic blood pressure fall and the following parameters determined before therapy: systolic blood pressure and its variability, heart rate (at rest and after stimulation by exercise or isoproterenol), cardiac output and total peripheral resistance, renin concentration (at rest and after stimulation) and urinary excretion of catecholamines and derivates.", "contents": "Predictive value of various parameters for the antihypertensive effect of the beta blocker ICI 66,082 (1). The antihypertensive effect of the new beta-blocker, ICI 66,082 was studied in 37 patients with renal or essential hypertension. A daily dose of 75 mg produced a significant antihypertensive effect and a further blood pressure decrease was obtained by increasing the daily dose up to 300 mg; at this treatment level, the antihypertensive effect averaged 29.4/24.0 mm Hg. Increasing the dose from 300 to 600 mg daily did not produce a significant additional blood pressure decrease. Six of the 37 patients retained fluid, producing a loss in the antihypertensive effect. No significant correlation was found between the percentage systolic blood pressure fall and the following parameters determined before therapy: systolic blood pressure and its variability, heart rate (at rest and after stimulation by exercise or isoproterenol), cardiac output and total peripheral resistance, renin concentration (at rest and after stimulation) and urinary excretion of catecholamines and derivates."}
{"id": "PMID:238481", "title": "The effect of clonidine and penbutolol, respectively on catecholamines in blood and urine, plasma renin activity and urinary aldosterone in hypertensive patients.", "content": "In various kinds of hypertension clonidine induced a decrease in urinary catecholamines, plasma renin activity and urinary aldosterone, concommitant with a fall in blood pressure and pulse rate in both short term and chronic studies. Furthermore, clonidine lowered the plasma levels of noradrenaline and adrenaline but a postural increase in upright position still occurred. The capacity to increase renin during salt restriction seemed mainatined. When clonidine was withdrawn all parameters returned to pretreatment levels but in some cases a marked rebound increase in catecholamine production was seen. --During clonidine the increase in catecholamines and renin after insulin induced hypoglycemia was largely abolished. Under basal conditions oral penbutolol induced a decrease of pule rate and blood pressure but no change in plasma or urinary catecholamines. During treatment plasma renin was suppressed at rest and after exercise. A work load, which led to only minor changes in blood catecholamines before treatment, was associated with a marked increase during penbutolol. Medication with penbutolol reduced the response in plasma catecholamines after hypoglycemia and renin activity remained low. Clonidine seems to act mainly by central inhibtion of symapthetic tone. Penbutolol probably acts mainly peripherally but may also have a central effect.", "contents": "The effect of clonidine and penbutolol, respectively on catecholamines in blood and urine, plasma renin activity and urinary aldosterone in hypertensive patients. In various kinds of hypertension clonidine induced a decrease in urinary catecholamines, plasma renin activity and urinary aldosterone, concommitant with a fall in blood pressure and pulse rate in both short term and chronic studies. Furthermore, clonidine lowered the plasma levels of noradrenaline and adrenaline but a postural increase in upright position still occurred. The capacity to increase renin during salt restriction seemed mainatined. When clonidine was withdrawn all parameters returned to pretreatment levels but in some cases a marked rebound increase in catecholamine production was seen. --During clonidine the increase in catecholamines and renin after insulin induced hypoglycemia was largely abolished. Under basal conditions oral penbutolol induced a decrease of pule rate and blood pressure but no change in plasma or urinary catecholamines. During treatment plasma renin was suppressed at rest and after exercise. A work load, which led to only minor changes in blood catecholamines before treatment, was associated with a marked increase during penbutolol. Medication with penbutolol reduced the response in plasma catecholamines after hypoglycemia and renin activity remained low. Clonidine seems to act mainly by central inhibtion of symapthetic tone. Penbutolol probably acts mainly peripherally but may also have a central effect."}
{"id": "PMID:238482", "title": "Centrally induced hypotension unreleated to alpha-adrenergic stimulation.", "content": "Central hypotension is induced by erythro-1-(1-[2-(1,4 - benzodioxan - 2 - yl) - 20H - ET] - 4 - piperidyl) - 2 - benzimidazolinone (R28935), as evidenced by local injections into the cisterna magna of anaesthetized dogs. This hypotensive effect is not inhibited by piperoxan, 100 mug/kg s.o. R28935, contrary to clonidine or norepinephrine, does not provoke vasoconstriction in the perfused isolated artery of the rabbit ear. Very low doses of R28935 antagonize vasoconstriction induced by KC1-depolarization. The centrally-induced hypotension is not due to alpha-adrenergic stimulation.", "contents": "Centrally induced hypotension unreleated to alpha-adrenergic stimulation. Central hypotension is induced by erythro-1-(1-[2-(1,4 - benzodioxan - 2 - yl) - 20H - ET] - 4 - piperidyl) - 2 - benzimidazolinone (R28935), as evidenced by local injections into the cisterna magna of anaesthetized dogs. This hypotensive effect is not inhibited by piperoxan, 100 mug/kg s.o. R28935, contrary to clonidine or norepinephrine, does not provoke vasoconstriction in the perfused isolated artery of the rabbit ear. Very low doses of R28935 antagonize vasoconstriction induced by KC1-depolarization. The centrally-induced hypotension is not due to alpha-adrenergic stimulation."}
{"id": "PMID:238483", "title": "[Cardiopulmonary effects after i.v. administration of maprotiline in the dog].", "content": "The cardiopulmonary effects of the antidepressive agent maprotiline were investigated in the dog. In ventilation experiments on dogs anaesthetized with chloralose, respiratory minute volume decreased by 5-10% shortly after intravenous injection of 1 and 3 mg/kg; acid-base-balance variables remained unchanged. After an intravenous dose of 10 mg/kg ineffective hyperventilation was observed, associated with a transient decrease of P-O2 and a slight increase in P-CO2 in the arterial blood. In cardiac-catheterization experiments on dogs anaesthetized with chloralose and morphine and receiving artificial respiration, an intravenous dose of 3 mg/kg maprotiline had no appreciable effect on the cardiovascular system, apart from a transient and slight, but statistically significant increase in pulmonary capillary pressure immediately after the injection. Anaesthesia was slightly deeper and more prolonged after the intravenous administration of maprotiline.", "contents": "[Cardiopulmonary effects after i.v. administration of maprotiline in the dog]. The cardiopulmonary effects of the antidepressive agent maprotiline were investigated in the dog. In ventilation experiments on dogs anaesthetized with chloralose, respiratory minute volume decreased by 5-10% shortly after intravenous injection of 1 and 3 mg/kg; acid-base-balance variables remained unchanged. After an intravenous dose of 10 mg/kg ineffective hyperventilation was observed, associated with a transient decrease of P-O2 and a slight increase in P-CO2 in the arterial blood. In cardiac-catheterization experiments on dogs anaesthetized with chloralose and morphine and receiving artificial respiration, an intravenous dose of 3 mg/kg maprotiline had no appreciable effect on the cardiovascular system, apart from a transient and slight, but statistically significant increase in pulmonary capillary pressure immediately after the injection. Anaesthesia was slightly deeper and more prolonged after the intravenous administration of maprotiline."}
{"id": "PMID:238484", "title": "Rheumatoid arthritis associated with hyperviscosity syndrome and intermediate complex formation.", "content": "A patient with long-standing rheumatoid arthritis developed hyperviscosity syndrome that correlated with the presence of abundant intermediate complexes in plasma. The intermediate complexes were isolated, and evidence is presented that these complexes are composed predominantly of igG-rheumatoid factor.", "contents": "Rheumatoid arthritis associated with hyperviscosity syndrome and intermediate complex formation. A patient with long-standing rheumatoid arthritis developed hyperviscosity syndrome that correlated with the presence of abundant intermediate complexes in plasma. The intermediate complexes were isolated, and evidence is presented that these complexes are composed predominantly of igG-rheumatoid factor."}
{"id": "PMID:238485", "title": "Rapid method for eluting IgG antibodies from erythrocytes coated with anti-Rh immune antibodies.", "content": "A method for eluting IgG antibodies from erythrocytes coated with anti-Rh immune antibodies has been developed, using temperature 56 degrees C as decomplexing factor and ion-exchange on DEAE Sephadex A-50 as antigen-binding factor.", "contents": "Rapid method for eluting IgG antibodies from erythrocytes coated with anti-Rh immune antibodies. A method for eluting IgG antibodies from erythrocytes coated with anti-Rh immune antibodies has been developed, using temperature 56 degrees C as decomplexing factor and ion-exchange on DEAE Sephadex A-50 as antigen-binding factor."}
{"id": "PMID:238486", "title": "Studies on stimulation and properties of antiglobulin antibodies. II. Antiglobulin antibodies against homologous globulins and antigens of thermally denatured autologous sera in the sera of rabbits immunized with various antigens.", "content": "Sera of 48 rabbits after long-term immunization with suspensions of Diplococcus pneumoniae, Klebsiella friedl\u00e4nderi, Proteus OX19 and solution of bovine albumin were examined for antibodies reacting with homologous gamma-globulins and antigens of thermally denatured autologous sera. Appearance of antibodies of this type was related to duration of immunization, but not related to the type of antigen used. The experimental results were explained as a result of altered antigenic properties of antibodies following reaction with homologous antigen.", "contents": "Studies on stimulation and properties of antiglobulin antibodies. II. Antiglobulin antibodies against homologous globulins and antigens of thermally denatured autologous sera in the sera of rabbits immunized with various antigens. Sera of 48 rabbits after long-term immunization with suspensions of Diplococcus pneumoniae, Klebsiella friedl\u00e4nderi, Proteus OX19 and solution of bovine albumin were examined for antibodies reacting with homologous gamma-globulins and antigens of thermally denatured autologous sera. Appearance of antibodies of this type was related to duration of immunization, but not related to the type of antigen used. The experimental results were explained as a result of altered antigenic properties of antibodies following reaction with homologous antigen."}
{"id": "PMID:238487", "title": "Rat interferons. III. Antiviral activity and effect of \"priming\" on interferon production in homologous and heterologous cell lines.", "content": "Studies on interferon from rat serum sensitive to pH 2-0 showed the following: 1) Its action is stronger in cultures of heterologous L cells than in rat fibroblast cultures. 2) Resistance acquired under the influence of interferon lasts longer in a heterologous than in a homologous system. 3) Actinomycin D added to cultures after 4 hours of contact with interferon inhibits its activity in L cells, and potentiates its activity in RE cells. 4) In rat embryonic cells treated with interferon, interferon production following induction with ND virus is blocked. Similar blocking was observed in cultures of L cells after 24-hour priming; after 6 hours of exposure of L cells to rat interferon, on the other hand, production of interferon was enhanced.", "contents": "Rat interferons. III. Antiviral activity and effect of \"priming\" on interferon production in homologous and heterologous cell lines. Studies on interferon from rat serum sensitive to pH 2-0 showed the following: 1) Its action is stronger in cultures of heterologous L cells than in rat fibroblast cultures. 2) Resistance acquired under the influence of interferon lasts longer in a heterologous than in a homologous system. 3) Actinomycin D added to cultures after 4 hours of contact with interferon inhibits its activity in L cells, and potentiates its activity in RE cells. 4) In rat embryonic cells treated with interferon, interferon production following induction with ND virus is blocked. Similar blocking was observed in cultures of L cells after 24-hour priming; after 6 hours of exposure of L cells to rat interferon, on the other hand, production of interferon was enhanced."}
{"id": "PMID:238488", "title": "Proteins in mouse embryonic cell (MEC) culture fluids following interferon induction.", "content": "A study was made on the proteins and interferon activity in supernatant culture fluids from mouse fibroblast cultures induced with Newcastle disease virus, and in controls. The studied materials showed low protein content, the concentration of proteins depending on the length of time from induction to their collection. Proteins from induced and control cultures were separated on CM-Sephadex C-50 and by electrophoresis in polyacrylamide gel. No difference was found in the character of proteins from control materials and from materials induced 24 hours after infection; the elution profile was the same, and the distribution of electrophoretic fractions was similar. Interferon activity was not accompanied by the appearance of a new protein fraction. However, 5--10 hours after induction differences were noted in electrophoretic mobility and a marked reduction in the number of protein fractions occurred in control and stimulated culture fluids.", "contents": "Proteins in mouse embryonic cell (MEC) culture fluids following interferon induction. A study was made on the proteins and interferon activity in supernatant culture fluids from mouse fibroblast cultures induced with Newcastle disease virus, and in controls. The studied materials showed low protein content, the concentration of proteins depending on the length of time from induction to their collection. Proteins from induced and control cultures were separated on CM-Sephadex C-50 and by electrophoresis in polyacrylamide gel. No difference was found in the character of proteins from control materials and from materials induced 24 hours after infection; the elution profile was the same, and the distribution of electrophoretic fractions was similar. Interferon activity was not accompanied by the appearance of a new protein fraction. However, 5--10 hours after induction differences were noted in electrophoretic mobility and a marked reduction in the number of protein fractions occurred in control and stimulated culture fluids."}
{"id": "PMID:238489", "title": "Some biochemical indices of posttransfusion shock induced under protection by selective hypothermia of the brain.", "content": "Biochemical disorders accompanying posttransfusion shock in cats under protection by selective cerebral hypothermia, by our own method was studied in cats. In 11 of 22 cats, selective cerebral hypothermia was performed before transfusion of human group A blood. In 11 control cats, transfusions were made without prior selective cerebral hypothermia. The following parameters were determined in venous blood: pH, pCO2, HCO3, content and excess of buffer bases. Selective cerebral hypothermia diminished mortality in cats in posttransfusion shock and reduced the intensity of the biochemical changes accompanying shock.", "contents": "Some biochemical indices of posttransfusion shock induced under protection by selective hypothermia of the brain. Biochemical disorders accompanying posttransfusion shock in cats under protection by selective cerebral hypothermia, by our own method was studied in cats. In 11 of 22 cats, selective cerebral hypothermia was performed before transfusion of human group A blood. In 11 control cats, transfusions were made without prior selective cerebral hypothermia. The following parameters were determined in venous blood: pH, pCO2, HCO3, content and excess of buffer bases. Selective cerebral hypothermia diminished mortality in cats in posttransfusion shock and reduced the intensity of the biochemical changes accompanying shock."}
{"id": "PMID:238490", "title": "Staged orchiorrhaphy. Therapeutic procedure in cryptorchic testicle with a short spermatic cord.", "content": "In 62 planned staged orchiorrhaphies for a \"short\" spermatic cord, satisfactory location of the testicle following the second operation was achieved in 90% of cases. The testicle was atrophic and had to be excised in only 3.2%. After a follow-up period of two to ten years, the testicle remained satisfactorily located in 77% of cases; adequate size and configuration of the testicle (compared to the contralateral side) was found in 64.5%. In 17%, a partial or complete atrophy developed. No correlation was found between the initial size of the testicle and the late results. It is advocated, therefore, that excision be avoided unless definite atrophy exists. Planned staged orchiorrhaphy is recommended for testicles in high locations that are difficult to bring down. The late preschool period (5 to 6 years) is suggested as the optimal age for the first attempt at orchiorrhaphy and the second stage two years later, if required.", "contents": "Staged orchiorrhaphy. Therapeutic procedure in cryptorchic testicle with a short spermatic cord. In 62 planned staged orchiorrhaphies for a \"short\" spermatic cord, satisfactory location of the testicle following the second operation was achieved in 90% of cases. The testicle was atrophic and had to be excised in only 3.2%. After a follow-up period of two to ten years, the testicle remained satisfactorily located in 77% of cases; adequate size and configuration of the testicle (compared to the contralateral side) was found in 64.5%. In 17%, a partial or complete atrophy developed. No correlation was found between the initial size of the testicle and the late results. It is advocated, therefore, that excision be avoided unless definite atrophy exists. Planned staged orchiorrhaphy is recommended for testicles in high locations that are difficult to bring down. The late preschool period (5 to 6 years) is suggested as the optimal age for the first attempt at orchiorrhaphy and the second stage two years later, if required."}
{"id": "PMID:238491", "title": "Effect of alkaline maintenance medium upon the growth of rabies virus in chick embryo cells.", "content": "HEP Flury strain of rabies virus was propagated in chick embryo cells under maintenance media of different pH. It was found that viral growth was better and reached a markedly higher maximum titer when the initial pH of maintenance medium was 8.2 to 9.0 than when it was 7.4. The enhancement of viral growth was not ascribable to mere neutralization of acids produced from infected cells, because the different media became almost equally neutral within an early phase of growth curve. Serial passage of the virus in chick embryo cells using pH 8.2 maintenance medium resulted in altered growth characteristics of the progeny virus; first, the virus so passaged could now grow equally well under alkaline and neutral maintenance media, and, secondly, autointerference observable with the parent virus eventually lowered virus yield when neutral maintenance medium was used, but this effect of undiluted passage was eliminated by the use of pH 8.2 maintenance medium.", "contents": "Effect of alkaline maintenance medium upon the growth of rabies virus in chick embryo cells. HEP Flury strain of rabies virus was propagated in chick embryo cells under maintenance media of different pH. It was found that viral growth was better and reached a markedly higher maximum titer when the initial pH of maintenance medium was 8.2 to 9.0 than when it was 7.4. The enhancement of viral growth was not ascribable to mere neutralization of acids produced from infected cells, because the different media became almost equally neutral within an early phase of growth curve. Serial passage of the virus in chick embryo cells using pH 8.2 maintenance medium resulted in altered growth characteristics of the progeny virus; first, the virus so passaged could now grow equally well under alkaline and neutral maintenance media, and, secondly, autointerference observable with the parent virus eventually lowered virus yield when neutral maintenance medium was used, but this effect of undiluted passage was eliminated by the use of pH 8.2 maintenance medium."}
{"id": "PMID:238492", "title": "[Isolation of surface antigens of influenza virus A/Hong Kong 1/68 (H3N2) by density gradient fractionation with a new carboxypolypeptidase (author's transl)].", "content": "Isolation of pure neuraminidase and hemagglutinin from influenza virus A/Hong Kong 1/68 (H3N2) can be achieved using the coupled action of a new carboxypolypeptidase from Streptomyces fradiae and sodium dodecyl sulfate (SDS). Biochemical, physical and physico-chemical studies showed that the two molecules are in pure form and of glycoproteic nature.", "contents": "[Isolation of surface antigens of influenza virus A/Hong Kong 1/68 (H3N2) by density gradient fractionation with a new carboxypolypeptidase (author's transl)]. Isolation of pure neuraminidase and hemagglutinin from influenza virus A/Hong Kong 1/68 (H3N2) can be achieved using the coupled action of a new carboxypolypeptidase from Streptomyces fradiae and sodium dodecyl sulfate (SDS). Biochemical, physical and physico-chemical studies showed that the two molecules are in pure form and of glycoproteic nature."}
{"id": "PMID:238496", "title": "Graft-versus-host reaction (GVHR). A case report suggesting GVHR occurred as a result of maternofetal cell transfer.", "content": "A female infant with combined immune deficiency syndrome exhibited graft-versus-host reaction (GVHR) clinically during the nine weeks of her life. Pathologically, the first clue for GVHR was the lymphohistiocytic dermal and epidermal infiltrate with single cell necrobiosis seen on a skin biopsy specimen at 6 weeks of age. Two days before death, she received irradiated (3,500 rads) whole blood and plasma with specific antibodies against mother's lymphocytes, which was the first introduction of an allogenic hematopoietic substance. This suggests that the GVHR, which was confirmed at autopsy, occurred as the result of maternofetal cell transfer in utero or at time of delivery.", "contents": "Graft-versus-host reaction (GVHR). A case report suggesting GVHR occurred as a result of maternofetal cell transfer. A female infant with combined immune deficiency syndrome exhibited graft-versus-host reaction (GVHR) clinically during the nine weeks of her life. Pathologically, the first clue for GVHR was the lymphohistiocytic dermal and epidermal infiltrate with single cell necrobiosis seen on a skin biopsy specimen at 6 weeks of age. Two days before death, she received irradiated (3,500 rads) whole blood and plasma with specific antibodies against mother's lymphocytes, which was the first introduction of an allogenic hematopoietic substance. This suggests that the GVHR, which was confirmed at autopsy, occurred as the result of maternofetal cell transfer in utero or at time of delivery."}
{"id": "PMID:238498", "title": "A new analysis of allogeneic interactions.", "content": "Allogeneic reactions have conventionally been considered as typical immune responses by one population of cells to antigens present on the other. This view is inadequate, since it does not explain many features of these reactions, among which are: (1) reactivity is much higher between different strains within a species than between species, in spite of the much greater antigenic disparity in the second case; (2) a very high proportion of cells may respond to allogeneic stimuli; (3) major histocompatibility differences are not essential for vigorous allogeneic reactions; (4) the responding population need not be immunologically competent to respond to antigens of the stimulating population; (5) the stimulating population must be both metabolically active and immunocompetent. We have tried to produce a model of cell interaction which will account for these and other anomalies, which at the same time explaining both normal antigenic stimulation (through cell-cell cooperation) and allogeneic interactions as examples of the same basic mechanisms. The model is based on the Bretscher-Cohn scheme of cell interaction. An allogeneic reaction is seen as having two stages: (1) Cells come together when antibody receptors on cells of one population combine with antigens on cells of the other. To this extent, our model is the same as the conventional one. It need not be the responding population which has the receptors, however. (2) A species-specific proliferation signal passes between the cells. This is the same signal as is involved in normal antibody induction. Even antigen-receptor bonds which are very weak may result in effective stimulation of one or both partners because of enhancing effect of this signal, and because the antigens involved are probably repeated over the cell surface, enabling multipoint binding. This explains the very proportions of cells which proliferate. The exact outcome of any allogeneic interaction will depend on which of the two populations have antibody receptors for antigens on the other, which can produce the proliferative stimulus, and which can respond to either the proliferative signal alone or to this stimulus plus antigen.", "contents": "A new analysis of allogeneic interactions. Allogeneic reactions have conventionally been considered as typical immune responses by one population of cells to antigens present on the other. This view is inadequate, since it does not explain many features of these reactions, among which are: (1) reactivity is much higher between different strains within a species than between species, in spite of the much greater antigenic disparity in the second case; (2) a very high proportion of cells may respond to allogeneic stimuli; (3) major histocompatibility differences are not essential for vigorous allogeneic reactions; (4) the responding population need not be immunologically competent to respond to antigens of the stimulating population; (5) the stimulating population must be both metabolically active and immunocompetent. We have tried to produce a model of cell interaction which will account for these and other anomalies, which at the same time explaining both normal antigenic stimulation (through cell-cell cooperation) and allogeneic interactions as examples of the same basic mechanisms. The model is based on the Bretscher-Cohn scheme of cell interaction. An allogeneic reaction is seen as having two stages: (1) Cells come together when antibody receptors on cells of one population combine with antigens on cells of the other. To this extent, our model is the same as the conventional one. It need not be the responding population which has the receptors, however. (2) A species-specific proliferation signal passes between the cells. This is the same signal as is involved in normal antibody induction. Even antigen-receptor bonds which are very weak may result in effective stimulation of one or both partners because of enhancing effect of this signal, and because the antigens involved are probably repeated over the cell surface, enabling multipoint binding. This explains the very proportions of cells which proliferate. The exact outcome of any allogeneic interaction will depend on which of the two populations have antibody receptors for antigens on the other, which can produce the proliferative stimulus, and which can respond to either the proliferative signal alone or to this stimulus plus antigen."}
{"id": "PMID:238499", "title": "Purification, properties and kinetics of sheep and human renin substrates.", "content": "Sheep plasma renin substrate was purified 1,200-fold by using nephrectomised sheep plasma, followed by DEAE-Sephadex chromatography and gel filtration. The purified substrate contained 8 mu-g angiotensin II/mg protein and had an estimated molecular weight of 52,000. The kinetic characteristics of the purified substrate were identical both to those of unpurified nephrectomised sheep plasma and to normal sheep plasma substrates. At pH 7.5, K-m of the human renin-sheep substrate reaction was 0.29 mu-M and for sheep renin-sheep substrate, 2.0 mu-M. Sheep substrate was susceptible to peptic digestion with generation of pepsitensin. Human renin substrate was less readily purified. DEAE-Sephadex chromatography of plasma from pregnant women at 36-40 weeks' gestation produced a 70-fold increase in purity (0.9 mu-g angiotensin II/mg protein). No further increase was achieved with gel filtration. Human renin substrate behaved as a larger (mol. wt. 82,000) more anionic protein than sheep substrate and was resistant to the proteolytic actions of both pepsin and sheep renin. K-m for the human renin-human substrate reaction was high and could not be accurately determined (range 3-8 mu-M, mean 5.7 mu-M). The presence of human substrate in a human renin-sheep substrate system did not alter the measured initial velocity. In both sheep and man, the normal concentration of renin substrate is considerably less than K-m and must therefore be considered a determinant of angiotensin production rate in vivo.", "contents": "Purification, properties and kinetics of sheep and human renin substrates. Sheep plasma renin substrate was purified 1,200-fold by using nephrectomised sheep plasma, followed by DEAE-Sephadex chromatography and gel filtration. The purified substrate contained 8 mu-g angiotensin II/mg protein and had an estimated molecular weight of 52,000. The kinetic characteristics of the purified substrate were identical both to those of unpurified nephrectomised sheep plasma and to normal sheep plasma substrates. At pH 7.5, K-m of the human renin-sheep substrate reaction was 0.29 mu-M and for sheep renin-sheep substrate, 2.0 mu-M. Sheep substrate was susceptible to peptic digestion with generation of pepsitensin. Human renin substrate was less readily purified. DEAE-Sephadex chromatography of plasma from pregnant women at 36-40 weeks' gestation produced a 70-fold increase in purity (0.9 mu-g angiotensin II/mg protein). No further increase was achieved with gel filtration. Human renin substrate behaved as a larger (mol. wt. 82,000) more anionic protein than sheep substrate and was resistant to the proteolytic actions of both pepsin and sheep renin. K-m for the human renin-human substrate reaction was high and could not be accurately determined (range 3-8 mu-M, mean 5.7 mu-M). The presence of human substrate in a human renin-sheep substrate system did not alter the measured initial velocity. In both sheep and man, the normal concentration of renin substrate is considerably less than K-m and must therefore be considered a determinant of angiotensin production rate in vivo."}
{"id": "PMID:238500", "title": "Cardiopulmonary changes following 24-36 hours of hyperoxia.", "content": "Cardiopulmonary variables were studied in rabbits breathing room air following 24-36 h of 100 percent 0-2 exposure. Initially, arterial pH and P-co-2 remained within normal limits while arterial P-0-2 decreased significantly. Cardiac output and oxygen consumption increased significantly. Static lung compliance was decreased, and histologic examination showed pulmonary hemorrhage, atelectasis, and adema. Myocardial function under these conditions was restored, and the myocardium was able to produce a compensatory increase in cardiac output. Therefore, changes in myocardial function, as related to oxygen toxicity, are reversable phenomena.", "contents": "Cardiopulmonary changes following 24-36 hours of hyperoxia. Cardiopulmonary variables were studied in rabbits breathing room air following 24-36 h of 100 percent 0-2 exposure. Initially, arterial pH and P-co-2 remained within normal limits while arterial P-0-2 decreased significantly. Cardiac output and oxygen consumption increased significantly. Static lung compliance was decreased, and histologic examination showed pulmonary hemorrhage, atelectasis, and adema. Myocardial function under these conditions was restored, and the myocardium was able to produce a compensatory increase in cardiac output. Therefore, changes in myocardial function, as related to oxygen toxicity, are reversable phenomena."}
{"id": "PMID:238501", "title": "Polymorphism at the alpha-glycerophosphate dehydrogenase locus in Drosophila melanogaster. I. Properties of adult allozymes.", "content": "A biochemical comparison was made between alpha-glycerophosphate dehydrogenase allozymes from Drosophila melanogaster. Enzymes extracted from the three major genotypes were indistinguishable in terms of their pH optima and thermal stabilities. Distinctive differences were observed for three parameters; temperature dependence of specific activity, temperature dependence of K-m, and reaction rate constancy over a physiological temperature range. These results are discussed in terms of a model of balancing selection and the existence of spatial and temporal allele frequency clines in natural populations.", "contents": "Polymorphism at the alpha-glycerophosphate dehydrogenase locus in Drosophila melanogaster. I. Properties of adult allozymes. A biochemical comparison was made between alpha-glycerophosphate dehydrogenase allozymes from Drosophila melanogaster. Enzymes extracted from the three major genotypes were indistinguishable in terms of their pH optima and thermal stabilities. Distinctive differences were observed for three parameters; temperature dependence of specific activity, temperature dependence of K-m, and reaction rate constancy over a physiological temperature range. These results are discussed in terms of a model of balancing selection and the existence of spatial and temporal allele frequency clines in natural populations."}
{"id": "PMID:238502", "title": "Genetic expression of beta-mannosidase activity in different tissues of mice.", "content": "Beta-Mannosidase activity of liver, kidney, and spleen of two inbred strains of mice and their crosses has been assayed with the synthetic aubstrate p-nitrophenyl-beta-d-mannoside. Activity is low in C57BL/Kl mice and high in DBA/2/Kl mice. Hybrid animals have intermediate levels of beta-mannosidase activity. Segregation of enzyme activities occurs in the F-2 and backcross generations, and there are good correlations between acitities in the three tissuses of F-2 and backcross animals. Some evidence points to a single gene difference in crosses between C57BL and DBA with respect to this mannosidase variation. Curves for enzyme activities at different substrate concentrations and pHs obtained with preparations from DBA and C57BL mice show some differences. These are interpreted as a possible strain variation in a structural gene for this enzyme.", "contents": "Genetic expression of beta-mannosidase activity in different tissues of mice. Beta-Mannosidase activity of liver, kidney, and spleen of two inbred strains of mice and their crosses has been assayed with the synthetic aubstrate p-nitrophenyl-beta-d-mannoside. Activity is low in C57BL/Kl mice and high in DBA/2/Kl mice. Hybrid animals have intermediate levels of beta-mannosidase activity. Segregation of enzyme activities occurs in the F-2 and backcross generations, and there are good correlations between acitities in the three tissuses of F-2 and backcross animals. Some evidence points to a single gene difference in crosses between C57BL and DBA with respect to this mannosidase variation. Curves for enzyme activities at different substrate concentrations and pHs obtained with preparations from DBA and C57BL mice show some differences. These are interpreted as a possible strain variation in a structural gene for this enzyme."}
{"id": "PMID:238503", "title": "The identification and biosynthesis of siderochromes formed by Micrococcus denitrificans.", "content": "1. Micrococcus denitrificans excretes three catechol-containing compounds, which can bind iron, when grown aerobically and anaerobically in media deficient in iron, and anaerobically in medium with a high concentration of Ca2+. 2. One of these compounds was identified as 2,3-dihydroxybenzoic acid (compound I), and the other two were tentatively identified as N1N8-bis-(2,3-dihydroxybenzoyl)spermidine (compound II) and 2-hydroxybenzoyl-N-L-threonyl-N4[N1N8-bis-(2,3-dihydroxybenzoyl)]spermidine (compound III). 3. The equimolar ferric complex of compound III was prepared; compound III also forms complexes with Al3+, Cr3+ and Co2+ ions. 4. Cell-free extracts from iron-deficient organisms catalyse the formation of compound II from 2,3-dihydroxybenzoic acid and spermidine, and of compound III from compound II, L-threonine and 2-hydroxybenzoic acid; both reactions require ATP and dithiothreitol, and Mg2+ stimulates activity. The enzyme system catalysing the formation of compound II has optimum activity at pH 8.8 Fe2+ (35muM), Fe3+ (35muM) and Al3+ (65muM) inhibit the reaction by 50 percent. The enzyme system forming compound III has optimum activity at pH 8.6. Fe2+ (110 muM), Fe3+ (110 muM) and Al3+ (135 muM) inhibit the reaction by 50 percent. 5. At least two proteins are required for the formation of compound II, and another two proteins for its conversion into compound III. 6. The changes in the activities of these two systems were followed after cultures became deficient in iron. 7. Ferrous 1,10-phenanthroline is formed when a cell-free extract from iron-deficient cells is incubated with the ferric complex of compound III, succinate, NADH and 1,10-phenanthroline under N2.", "contents": "The identification and biosynthesis of siderochromes formed by Micrococcus denitrificans. 1. Micrococcus denitrificans excretes three catechol-containing compounds, which can bind iron, when grown aerobically and anaerobically in media deficient in iron, and anaerobically in medium with a high concentration of Ca2+. 2. One of these compounds was identified as 2,3-dihydroxybenzoic acid (compound I), and the other two were tentatively identified as N1N8-bis-(2,3-dihydroxybenzoyl)spermidine (compound II) and 2-hydroxybenzoyl-N-L-threonyl-N4[N1N8-bis-(2,3-dihydroxybenzoyl)]spermidine (compound III). 3. The equimolar ferric complex of compound III was prepared; compound III also forms complexes with Al3+, Cr3+ and Co2+ ions. 4. Cell-free extracts from iron-deficient organisms catalyse the formation of compound II from 2,3-dihydroxybenzoic acid and spermidine, and of compound III from compound II, L-threonine and 2-hydroxybenzoic acid; both reactions require ATP and dithiothreitol, and Mg2+ stimulates activity. The enzyme system catalysing the formation of compound II has optimum activity at pH 8.8 Fe2+ (35muM), Fe3+ (35muM) and Al3+ (65muM) inhibit the reaction by 50 percent. The enzyme system forming compound III has optimum activity at pH 8.6. Fe2+ (110 muM), Fe3+ (110 muM) and Al3+ (135 muM) inhibit the reaction by 50 percent. 5. At least two proteins are required for the formation of compound II, and another two proteins for its conversion into compound III. 6. The changes in the activities of these two systems were followed after cultures became deficient in iron. 7. Ferrous 1,10-phenanthroline is formed when a cell-free extract from iron-deficient cells is incubated with the ferric complex of compound III, succinate, NADH and 1,10-phenanthroline under N2."}
{"id": "PMID:238504", "title": "Biosynthesis of caffeine by tea-leaf extracts. Enzymic formation of theobromine from 7-methylxanthine and of caffeine from theobromine.", "content": "1. Extracts prepared from tea leaves with Polyclar AT (insoluble polyvinylpyrrolidine) contained two methyltransferase activities catalysing the transfer of methyl groups from S-adenosylmethionine to 7-methylxanthine, producing theobromine, and to theobromine, producing caffeine. 2. The methyltransferases exhibited the same pH optimum (8.4) and a similar pattern of effects by metal ions, thiol inhibitors and metal-chelating reagents, both for theobromine and caffeine synthesis. Mg2+, Mn2+ and Ca2+ slightly stimulated enzyme activity but they were not essential. Paraxanthine was shown to be most active among methylxanthines, as the methyl acceptor. However, the formation of paraxanthine from 1-methylxanthine was very low and that from 7-methylxanthine was nil, suggesting that the synthesis of caffeine from paraxanthine is of little importance in intact plants. Xanthine, xanthosine, XMP and hypoxanthine were all inactive as methyl acceptors, whereas [2(-14)C]xanthine and [8(-14)C]hypoxanthine were catabolized to allantoin and urea by tea-leaf extracts. The apparent Km values are as follows: 7-methylxanthine, 1.0 times 10(-14)M; theobromine, 1.0 times 10(-3)M; paraxanthine, 0.2 times 10(-3)M; S-adenosylmethionine, 0.25 times 10(-4)M (with each of the three substrates). 3. The results suggest that the pathway for caffeine biosynthesis is as follows: 7-methylxanthine leads to theobromine leads to caffeine. In contrast, it is suggested that theophylline is synthesized from 1-methylxanthine. The methyl groups of the purine ring of caffeine are all derived directly from the methyl group of S-adenosylmethionine. Little is known about the pathways leading to the formation of 7-methylxanthine. 4. A good correlation between caffeine synthesis and shoot formation or growth of tea seedlings was shown, suggesting that the methylating systems in caffeine synthesis are closely associated with purine nucleotide and nucleic acid metabolism in tea plants.", "contents": "Biosynthesis of caffeine by tea-leaf extracts. Enzymic formation of theobromine from 7-methylxanthine and of caffeine from theobromine. 1. Extracts prepared from tea leaves with Polyclar AT (insoluble polyvinylpyrrolidine) contained two methyltransferase activities catalysing the transfer of methyl groups from S-adenosylmethionine to 7-methylxanthine, producing theobromine, and to theobromine, producing caffeine. 2. The methyltransferases exhibited the same pH optimum (8.4) and a similar pattern of effects by metal ions, thiol inhibitors and metal-chelating reagents, both for theobromine and caffeine synthesis. Mg2+, Mn2+ and Ca2+ slightly stimulated enzyme activity but they were not essential. Paraxanthine was shown to be most active among methylxanthines, as the methyl acceptor. However, the formation of paraxanthine from 1-methylxanthine was very low and that from 7-methylxanthine was nil, suggesting that the synthesis of caffeine from paraxanthine is of little importance in intact plants. Xanthine, xanthosine, XMP and hypoxanthine were all inactive as methyl acceptors, whereas [2(-14)C]xanthine and [8(-14)C]hypoxanthine were catabolized to allantoin and urea by tea-leaf extracts. The apparent Km values are as follows: 7-methylxanthine, 1.0 times 10(-14)M; theobromine, 1.0 times 10(-3)M; paraxanthine, 0.2 times 10(-3)M; S-adenosylmethionine, 0.25 times 10(-4)M (with each of the three substrates). 3. The results suggest that the pathway for caffeine biosynthesis is as follows: 7-methylxanthine leads to theobromine leads to caffeine. In contrast, it is suggested that theophylline is synthesized from 1-methylxanthine. The methyl groups of the purine ring of caffeine are all derived directly from the methyl group of S-adenosylmethionine. Little is known about the pathways leading to the formation of 7-methylxanthine. 4. A good correlation between caffeine synthesis and shoot formation or growth of tea seedlings was shown, suggesting that the methylating systems in caffeine synthesis are closely associated with purine nucleotide and nucleic acid metabolism in tea plants."}
{"id": "PMID:238506", "title": "The stoicheiometry of the absorption of protons with phosphate and L-glutamate by yeasts of the genus Saccharomyces.", "content": "1. A study was made of the pH changes occurring when 0.1-4 mumol of glutamate, phosphate and certain phosphate esters was added at about pH 4.8 to washed cell preparations (50 mg dry wt.) of strains of Saccharomyces. The system also contained deoxyglucose and antimycin to inhibit energy metabolism and so prevent proton ejection from the yeast. 2. A strain of Sacc. carlsbergensis was grown in a chemostat with a limiting supply of phosphate in order to enhance the subsequent rate of phosphate transfer into the yeast. These preparations absorbed 0.2 mumol of phosphate with about 3 equiv. of protons/mol of phosphate. The charge balance was maintained by the efflux of 2 equiv. of K-+ from the yeast. 3. Larger amounts of phosphate were absorbed with fewer proton equivalents. 4. Arsenate and phosphate caused similar pH changes. 5. Glucose 6-phosphate, ATP and certain order phosphate esters each initiated a rise in pH, possibly because hydrolytic extracellular enzymes released phosphate that was subsequently absorbed. 6. Four strains of yeast were grown with glutamate as principal source of nitrogen. Each absorbed extra protons in the presence of L-glutamate. 7. One of them, a strain of Sacc. cerevisiae, absorbed 0.2 mumol of glutamate with 3equiv. of protons/mol of glutamate, and in these circumstances 1-2 equiv. of K-+ left the yeast cells. 8. The role of ionic gradients in the transport of these anions is discussed.", "contents": "The stoicheiometry of the absorption of protons with phosphate and L-glutamate by yeasts of the genus Saccharomyces. 1. A study was made of the pH changes occurring when 0.1-4 mumol of glutamate, phosphate and certain phosphate esters was added at about pH 4.8 to washed cell preparations (50 mg dry wt.) of strains of Saccharomyces. The system also contained deoxyglucose and antimycin to inhibit energy metabolism and so prevent proton ejection from the yeast. 2. A strain of Sacc. carlsbergensis was grown in a chemostat with a limiting supply of phosphate in order to enhance the subsequent rate of phosphate transfer into the yeast. These preparations absorbed 0.2 mumol of phosphate with about 3 equiv. of protons/mol of phosphate. The charge balance was maintained by the efflux of 2 equiv. of K-+ from the yeast. 3. Larger amounts of phosphate were absorbed with fewer proton equivalents. 4. Arsenate and phosphate caused similar pH changes. 5. Glucose 6-phosphate, ATP and certain order phosphate esters each initiated a rise in pH, possibly because hydrolytic extracellular enzymes released phosphate that was subsequently absorbed. 6. Four strains of yeast were grown with glutamate as principal source of nitrogen. Each absorbed extra protons in the presence of L-glutamate. 7. One of them, a strain of Sacc. cerevisiae, absorbed 0.2 mumol of glutamate with 3equiv. of protons/mol of glutamate, and in these circumstances 1-2 equiv. of K-+ left the yeast cells. 8. The role of ionic gradients in the transport of these anions is discussed."}
{"id": "PMID:238505", "title": "The effects of diet, lipolysis and limb ischaemia on the distribution of plasma tryptophan in the rat.", "content": "A non-linear relationship between the plasma non-esterified fatty acid concentration and the percentage of free plasma tryptophan was found in rats in different nutritional states, although non-esterified fatty acids are not the only factors determining the percentage of free tryptophan. This relationship was not seen in rats injured by limb ischaemia. The effect of drugs causing rapid increases in the plasma non-esterified fatty acid concentration was also studied. Isoprenaline decreased the total plasma tryptophan concentration. Dichloroisoprenaline caused a sustained increase in the plasma non-esterified fatty acid concentration which was accompanied by an increase in the concentration of free plasma tryptophan and followed by a fall in the concentration of total tryptophan. The loss of tryptophan from the plasma was attributed to an altered distribution of tryptophan in the extracellular space rather than to increased metabolism. This interpretation was supported by determinations of the irreversible disposal rate of plasma tryptophan which in uninjured rats was unaffected by the concentration of free plasma tryptophan. In the injured rats this rate was unaltered during limb ischaemia but was decreased after removal of the tourniquets; increased competition for tissue entry by other neutral amino acids and the fall in body temperature could be factors in this fall.", "contents": "The effects of diet, lipolysis and limb ischaemia on the distribution of plasma tryptophan in the rat. A non-linear relationship between the plasma non-esterified fatty acid concentration and the percentage of free plasma tryptophan was found in rats in different nutritional states, although non-esterified fatty acids are not the only factors determining the percentage of free tryptophan. This relationship was not seen in rats injured by limb ischaemia. The effect of drugs causing rapid increases in the plasma non-esterified fatty acid concentration was also studied. Isoprenaline decreased the total plasma tryptophan concentration. Dichloroisoprenaline caused a sustained increase in the plasma non-esterified fatty acid concentration which was accompanied by an increase in the concentration of free plasma tryptophan and followed by a fall in the concentration of total tryptophan. The loss of tryptophan from the plasma was attributed to an altered distribution of tryptophan in the extracellular space rather than to increased metabolism. This interpretation was supported by determinations of the irreversible disposal rate of plasma tryptophan which in uninjured rats was unaffected by the concentration of free plasma tryptophan. In the injured rats this rate was unaltered during limb ischaemia but was decreased after removal of the tourniquets; increased competition for tissue entry by other neutral amino acids and the fall in body temperature could be factors in this fall."}
{"id": "PMID:238540", "title": "[The Heidelberg capsule, an antacid of improved galenics].", "content": "By means of the Heidelberg capsule the influence of two different antacids on the acidity of gastric juice was measured in 16 normal test subjects. The antacidic combination drugs were Roha salt tablets (RSTB) containing herba absinthii 1.9 mg; fruct. anisi 35.5 mg; rhiz. calami 22.2 mg; bolus alba 14.0 mg; calcium phosphoricum 53.3 mg; magnesium sulfuricum 41.1 mg; calcium carbonicum 70.0 mg; magnesium carbonicum 42.0 mg; sodium bicarbonicum 1120 mg, and Roha gastric tablets (RMTB) with retarded release and containing fruct. anisi 40 mg; herba absinthii 3.2 mg; calcium carbonicum 688 mg; sodium bicarbonicum 480 mg; magnesium carbonicum 40 mg. Compared to the simple antacid RSTB, the duration of the neutralizing effect of the retarded RMTB was prolonged significantly by 300%.", "contents": "[The Heidelberg capsule, an antacid of improved galenics]. By means of the Heidelberg capsule the influence of two different antacids on the acidity of gastric juice was measured in 16 normal test subjects. The antacidic combination drugs were Roha salt tablets (RSTB) containing herba absinthii 1.9 mg; fruct. anisi 35.5 mg; rhiz. calami 22.2 mg; bolus alba 14.0 mg; calcium phosphoricum 53.3 mg; magnesium sulfuricum 41.1 mg; calcium carbonicum 70.0 mg; magnesium carbonicum 42.0 mg; sodium bicarbonicum 1120 mg, and Roha gastric tablets (RMTB) with retarded release and containing fruct. anisi 40 mg; herba absinthii 3.2 mg; calcium carbonicum 688 mg; sodium bicarbonicum 480 mg; magnesium carbonicum 40 mg. Compared to the simple antacid RSTB, the duration of the neutralizing effect of the retarded RMTB was prolonged significantly by 300%."}
{"id": "PMID:238541", "title": "[Changes in imipramine induced noradrenaline potentiation by varying activity of gastric juice under oral medication].", "content": "From the serial studies on imipramine dependent noradrenaline (NA) rise at different values of gastric acid with 336 registrations of blood pressure, it follows that a lawful relation exists between imipramine absorption and gastric juice acidity. At pH values of 3.5--6.0 a distinct decreased absorption of orally supplied imipramine was stated. After changing the pH value by acid substitution, a full absorption is reached. This state seems to be of special practical importance in the treatment of depression with thymoleptics.", "contents": "[Changes in imipramine induced noradrenaline potentiation by varying activity of gastric juice under oral medication]. From the serial studies on imipramine dependent noradrenaline (NA) rise at different values of gastric acid with 336 registrations of blood pressure, it follows that a lawful relation exists between imipramine absorption and gastric juice acidity. At pH values of 3.5--6.0 a distinct decreased absorption of orally supplied imipramine was stated. After changing the pH value by acid substitution, a full absorption is reached. This state seems to be of special practical importance in the treatment of depression with thymoleptics."}
{"id": "PMID:238542", "title": "Modification of the cardiostimulatory and coronary dilator effect of isopreenaline caused by etafenone.", "content": "Effect of Etafenone on the Cardisotimulatory (1) In the isolated  guinea-pig heart (Langedorff), 2'-[2-(diethylamino)-ethoxy]-3 -phenyl-propioheonoe  HCI (etafenone, Baxacor) produced a parital and non-competitive inhibition of the stiumulant actions of isoprenaline on glycogen phosphorylase, rate and amplitude of contraction, but did not reduce the increase in coronary flow. (2) In isolated cirular strips from bovine coronary arteries, etafeonoe reduced tension (ED 50 = 2.8 x 10-5M), and increased the relaxing effect of isoprenaline. (3) Etafeonoe inhbitied the acitivty of phosphodiesterase in vitro; the Ki value with the enzyme frombovine coronary arteries was 9.2x10-4M, which was 160-fold higher than the Ki for papaverine.(4) The results suggest that etafenone probably affects the myocardial as well as the coronary smoth muscle cell by a direct inhibitory effect on Caiinflux, which could accountfor the depressant effect and the non-competitive antagonism aginst isoprenaline  in  the heartas well as the relaxing action on coronary smooth  muscle. The inhibitory effect on phospodiesterase is likely to contribute to the relaxing action of etafenone by accumulation ofcyclic AMP.", "contents": "Modification of the cardiostimulatory and coronary dilator effect of isopreenaline caused by etafenone. Effect of Etafenone on the Cardisotimulatory (1) In the isolated  guinea-pig heart (Langedorff), 2'-[2-(diethylamino)-ethoxy]-3 -phenyl-propioheonoe  HCI (etafenone, Baxacor) produced a parital and non-competitive inhibition of the stiumulant actions of isoprenaline on glycogen phosphorylase, rate and amplitude of contraction, but did not reduce the increase in coronary flow. (2) In isolated cirular strips from bovine coronary arteries, etafeonoe reduced tension (ED 50 = 2.8 x 10-5M), and increased the relaxing effect of isoprenaline. (3) Etafeonoe inhbitied the acitivty of phosphodiesterase in vitro; the Ki value with the enzyme frombovine coronary arteries was 9.2x10-4M, which was 160-fold higher than the Ki for papaverine.(4) The results suggest that etafenone probably affects the myocardial as well as the coronary smoth muscle cell by a direct inhibitory effect on Caiinflux, which could accountfor the depressant effect and the non-competitive antagonism aginst isoprenaline  in  the heartas well as the relaxing action on coronary smooth  muscle. The inhibitory effect on phospodiesterase is likely to contribute to the relaxing action of etafenone by accumulation ofcyclic AMP."}
{"id": "PMID:238543", "title": "A potentially antianginal benzo [b]thiophene with an amiodarone-like haemodynamic profile.", "content": "L 9146 or 2-methyl-3(3,5 dimethyl-4-gamma-di-n-butylaminopropoxy-benzoyl)-benzo [b] thiophene is a substance belonging to the amiodarone series which induces in the anaesthetized dog a decrease of myocardial oxygen consumption which is mainly due to slowing of the heart rate and reduction in systemic blood pressure. L 9146 also enhances coronary blood flow. L 9146 has also antiadrenergic properties since catecholamine-induced hypertension, tachycardia and increase of myocardial oxygen consumption are markedly antagonized; these antiacrenergic effects are not due to a competitive blockade of the beta-adrenoceptors. L 9146 does not decrease cardiac output, but increases it appreciably in the initial phase of its action. Several findings indicate that when the intensity of certain properties is considered, l9146 is more active than aniodarone since only half the dose used with aniodarone is required to achieve a given level of action. The overall haemodynamic properties of L 9146, which are similar to those of amiodarone, are considered to be potentially valuable for the long-term treatment of angina pectoris.", "contents": "A potentially antianginal benzo [b]thiophene with an amiodarone-like haemodynamic profile. L 9146 or 2-methyl-3(3,5 dimethyl-4-gamma-di-n-butylaminopropoxy-benzoyl)-benzo [b] thiophene is a substance belonging to the amiodarone series which induces in the anaesthetized dog a decrease of myocardial oxygen consumption which is mainly due to slowing of the heart rate and reduction in systemic blood pressure. L 9146 also enhances coronary blood flow. L 9146 has also antiadrenergic properties since catecholamine-induced hypertension, tachycardia and increase of myocardial oxygen consumption are markedly antagonized; these antiacrenergic effects are not due to a competitive blockade of the beta-adrenoceptors. L 9146 does not decrease cardiac output, but increases it appreciably in the initial phase of its action. Several findings indicate that when the intensity of certain properties is considered, l9146 is more active than aniodarone since only half the dose used with aniodarone is required to achieve a given level of action. The overall haemodynamic properties of L 9146, which are similar to those of amiodarone, are considered to be potentially valuable for the long-term treatment of angina pectoris."}
{"id": "PMID:238544", "title": "A study of some beta-adrenoceptor blocking agents on skeletal muscle.", "content": "The effect of three recently introduced beta-adrenoceptor blockers practolol, USVC 6524 and Inpea was studied on various skeletal muscle preparations. Practoloo, USVC 6524 and Inpea produced a dose related inhibition of acetylcholine induced contractions of rectus abdominis muscle of frog. These drugs also blocked neuromuscular transmission when tested on in vitro rat phrenic nerve diaphragm preparation; the blockade was partially reversed by physotigmine, KCl and adrenaline and was potentiated by d-tubocurarine. In gastrocnemius sciatic muscle-nerve preparation only Inpea exhibited neuromuscular blocking activity, while practolol and USVC 6524 did not show any effect up to a dose of 10 mg/kg (intraarterially). The apparent discrepancies between the results of in vitro and in vivo experiments could not be adequately explained. It has been discussed that the neuromuscular blockade caused by presently investigated beta-adrenoceptor blocking agents is essentially due to curare-like activity and to a small extent may be due to local anaesthetic activity.", "contents": "A study of some beta-adrenoceptor blocking agents on skeletal muscle. The effect of three recently introduced beta-adrenoceptor blockers practolol, USVC 6524 and Inpea was studied on various skeletal muscle preparations. Practoloo, USVC 6524 and Inpea produced a dose related inhibition of acetylcholine induced contractions of rectus abdominis muscle of frog. These drugs also blocked neuromuscular transmission when tested on in vitro rat phrenic nerve diaphragm preparation; the blockade was partially reversed by physotigmine, KCl and adrenaline and was potentiated by d-tubocurarine. In gastrocnemius sciatic muscle-nerve preparation only Inpea exhibited neuromuscular blocking activity, while practolol and USVC 6524 did not show any effect up to a dose of 10 mg/kg (intraarterially). The apparent discrepancies between the results of in vitro and in vivo experiments could not be adequately explained. It has been discussed that the neuromuscular blockade caused by presently investigated beta-adrenoceptor blocking agents is essentially due to curare-like activity and to a small extent may be due to local anaesthetic activity."}
{"id": "PMID:238545", "title": "Nuclear magnetic resonance studies of anaesthetic interactions with haemoglobin.", "content": "The use of 270 MHz Fourier Transform nuclear magnetic resonance (NMR) spectrometer, combined with signal processing techniques to improve resolution, enabled proton resonances from the individual aromatic residues of haemoglobin to be distinguished. In the presence of clinical concentrations of the general anaesthetic drugs halothane and methoxyflurane, specific changes in the NMR spectrum can be distinguished which probably reflect local changes of conformation. When higher concentrations of anaesthetic are used, extensive changes in the NMR spectrum occur which are consistent with non-specific binding of the anaesthetic to the hydrophobic parts of the haemoglobin molecule.", "contents": "Nuclear magnetic resonance studies of anaesthetic interactions with haemoglobin. The use of 270 MHz Fourier Transform nuclear magnetic resonance (NMR) spectrometer, combined with signal processing techniques to improve resolution, enabled proton resonances from the individual aromatic residues of haemoglobin to be distinguished. In the presence of clinical concentrations of the general anaesthetic drugs halothane and methoxyflurane, specific changes in the NMR spectrum can be distinguished which probably reflect local changes of conformation. When higher concentrations of anaesthetic are used, extensive changes in the NMR spectrum occur which are consistent with non-specific binding of the anaesthetic to the hydrophobic parts of the haemoglobin molecule."}
{"id": "PMID:238546", "title": "Ventilation and blood-gas studies during experimentally produced Mendelson's syndrome in the dog.", "content": "Hydrochloric acid was instilled into the bronchial tree in anaesthetized dogs. A severe respiratory acidosis resulted. The metabolic component of acid-base balance was little affected.", "contents": "Ventilation and blood-gas studies during experimentally produced Mendelson's syndrome in the dog. Hydrochloric acid was instilled into the bronchial tree in anaesthetized dogs. A severe respiratory acidosis resulted. The metabolic component of acid-base balance was little affected."}
{"id": "PMID:238547", "title": "Hypertension in the immediate postoperative period.", "content": "Sixty patients out of 1,844 recovery room admissions had significant postoperative arterial hypertension. Nearly 60% of them had a history of hypertension. The postoperative hypertension usually began within 30 min from the end of operation and lasted about 2 hours. In 20% of the patients it lasted 3 hours or longer. Complications attributable to hypertension were confined to this latter group. The principal factors possibly contributing to the pressure elevations were pain (35%), hypercarbia (15%) and emergence excitement (16%). Ten of the patients (17%) had no demonstrable cause for hypertension. The hypertension in this group appeared to have a shorter and more benign course.", "contents": "Hypertension in the immediate postoperative period. Sixty patients out of 1,844 recovery room admissions had significant postoperative arterial hypertension. Nearly 60% of them had a history of hypertension. The postoperative hypertension usually began within 30 min from the end of operation and lasted about 2 hours. In 20% of the patients it lasted 3 hours or longer. Complications attributable to hypertension were confined to this latter group. The principal factors possibly contributing to the pressure elevations were pain (35%), hypercarbia (15%) and emergence excitement (16%). Ten of the patients (17%) had no demonstrable cause for hypertension. The hypertension in this group appeared to have a shorter and more benign course."}
{"id": "PMID:238548", "title": "The effect of intravenous premedication with lorazepam (ativan), pentobarbitone or diazepam on recall.", "content": "Sixty-nine patients undergoing regional anaesthesia were premedicated with either lorazepam (1, 2, 3 or 5 mg), diazepam (5 or 10 mg), pentobarbitone (50 mg) or placebo given i.v., on a double-blind, randomized basis. A simple yet rigorous protocol was used to test the effect of these drugs on anterograde recall. Lorazepam 3 and 5 mg was found to affect anterograde recall significantly. None of the other drugs tested affected recall.", "contents": "The effect of intravenous premedication with lorazepam (ativan), pentobarbitone or diazepam on recall. Sixty-nine patients undergoing regional anaesthesia were premedicated with either lorazepam (1, 2, 3 or 5 mg), diazepam (5 or 10 mg), pentobarbitone (50 mg) or placebo given i.v., on a double-blind, randomized basis. A simple yet rigorous protocol was used to test the effect of these drugs on anterograde recall. Lorazepam 3 and 5 mg was found to affect anterograde recall significantly. None of the other drugs tested affected recall."}
{"id": "PMID:238550", "title": "Calcium uptake into muscle of pigs susceptible to malignant hyperthermia: in vitro and in vivo studies with and without halothane.", "content": "MHS and normal pigs were anaesthetized with nitrous oxide and diazepam. Halothane 1% was then administered for 1 hr. Immediately before and immediately after the halothane inhalation, 10 g of vastus lateralis muscle was excised. SR was isolated from this muscle. Calcium accumulation by the MHS sarcoplasmic reticulum in the absence of halothane was greater than normal. Halothane in vitro produced a similar increase in calcium uptake into both the MHS and the normal SR. Halothane in vivo significantly reduced calcium accumulation by hyperthermic SR but had no significant effect on calcium uptake into the normal SR. Thus the action of halothane on the MHS sarcoplasmic reticulum is indirect, occurring only in the intact cell. It is possibly a result of the deleterious effect which lack of ATP, a low pH or a high temperature is likely to have on the calcium accumulating mechanism of the SR membrane. Our results suggest that the primary defects of porcine and human malignant hyperthermia are not entirely synonymous.", "contents": "Calcium uptake into muscle of pigs susceptible to malignant hyperthermia: in vitro and in vivo studies with and without halothane. MHS and normal pigs were anaesthetized with nitrous oxide and diazepam. Halothane 1% was then administered for 1 hr. Immediately before and immediately after the halothane inhalation, 10 g of vastus lateralis muscle was excised. SR was isolated from this muscle. Calcium accumulation by the MHS sarcoplasmic reticulum in the absence of halothane was greater than normal. Halothane in vitro produced a similar increase in calcium uptake into both the MHS and the normal SR. Halothane in vivo significantly reduced calcium accumulation by hyperthermic SR but had no significant effect on calcium uptake into the normal SR. Thus the action of halothane on the MHS sarcoplasmic reticulum is indirect, occurring only in the intact cell. It is possibly a result of the deleterious effect which lack of ATP, a low pH or a high temperature is likely to have on the calcium accumulating mechanism of the SR membrane. Our results suggest that the primary defects of porcine and human malignant hyperthermia are not entirely synonymous."}
{"id": "PMID:238551", "title": "Procaine in porcine malignant hyperthermia.", "content": "Serum creatine phosphokinase, rectal temperature and muscle pH at death were measured in three halothane-susceptible Landrace pigs. Two of the pigs were treated with procaine. Although the course of the syndrome was different in the treated pigs, procaine did not reverse the established malignant hyperthermia syndrome.", "contents": "Procaine in porcine malignant hyperthermia. Serum creatine phosphokinase, rectal temperature and muscle pH at death were measured in three halothane-susceptible Landrace pigs. Two of the pigs were treated with procaine. Although the course of the syndrome was different in the treated pigs, procaine did not reverse the established malignant hyperthermia syndrome."}
{"id": "PMID:238552", "title": "Pulmonary oxygen transfer during IPPV in man.", "content": "The efficiency of pulmonary oxygen transfer, measured as the difference between pulmonary end-capillary and arterial oxygen content, was assessed at several different inspired oxygen concentrations in 20 patients during intermittent positive pressure ventilation (IPPV) with oxygen/nitrogen mixtures. In only three of the patients did the patterns of response correspond with those predicted from iso-shunt and ventilation/perfusion mismatch models of lung function, in which it is assumed that oxygen exerts only a passive physical effect within the lungs. It is suggested that the pattern of response obtained during IPPV in the remaining 17 patients is explicable on the basis of an active physiological effect of oxygen such that an increasing alveolar oxygen partial pressure is associated with a progressive increase in the proportion of the pulmonary blood flow which bypasses ventilated alveoli. This \"hyperoxic shunt\", which is readily reversible, may be the result of redistribution of either ventilation or blood flow within the lung.", "contents": "Pulmonary oxygen transfer during IPPV in man. The efficiency of pulmonary oxygen transfer, measured as the difference between pulmonary end-capillary and arterial oxygen content, was assessed at several different inspired oxygen concentrations in 20 patients during intermittent positive pressure ventilation (IPPV) with oxygen/nitrogen mixtures. In only three of the patients did the patterns of response correspond with those predicted from iso-shunt and ventilation/perfusion mismatch models of lung function, in which it is assumed that oxygen exerts only a passive physical effect within the lungs. It is suggested that the pattern of response obtained during IPPV in the remaining 17 patients is explicable on the basis of an active physiological effect of oxygen such that an increasing alveolar oxygen partial pressure is associated with a progressive increase in the proportion of the pulmonary blood flow which bypasses ventilated alveoli. This \"hyperoxic shunt\", which is readily reversible, may be the result of redistribution of either ventilation or blood flow within the lung."}
{"id": "PMID:238553", "title": "A clinical comparison of AH8165 and pancuronium as muscle relaxants in patients undergoing cardiac surgery.", "content": "The non-depolarizing muscle relaxant AH8165 has been compared at two doses (0.5 and 1.0 mg/kg) with pancuronium (0.1 mg/kg) during induction of anaesthesia for patients having major cardiac surgery. After barbiturate-opiate premedication and thiopentone induction, administration of pancuronium was followed by no significant alteration in heart rate or arterial pressure. Both doses of AH8165 werr followed by significant tachycardia, and the higher dose by arterial hypotension. The lower dose of AH8165 was unsatisfactory for tracheal intubation, but the AH8165 1 mg/kg gave intubating conditions similar to those with pancuronium 0.1 mg/kg.", "contents": "A clinical comparison of AH8165 and pancuronium as muscle relaxants in patients undergoing cardiac surgery. The non-depolarizing muscle relaxant AH8165 has been compared at two doses (0.5 and 1.0 mg/kg) with pancuronium (0.1 mg/kg) during induction of anaesthesia for patients having major cardiac surgery. After barbiturate-opiate premedication and thiopentone induction, administration of pancuronium was followed by no significant alteration in heart rate or arterial pressure. Both doses of AH8165 werr followed by significant tachycardia, and the higher dose by arterial hypotension. The lower dose of AH8165 was unsatisfactory for tracheal intubation, but the AH8165 1 mg/kg gave intubating conditions similar to those with pancuronium 0.1 mg/kg."}
{"id": "PMID:238554", "title": "Mechanism of action of local anaesthetic agents and biotoxins.", "content": "Four current theories for the mechanism of action of local anaesthetics are that these drugs: (1) interfere with some chemical, such as acetylcholine, that is involved in nervous conduction; (2) alter the density of fixed charges on the surface of the membrane; (3) cause an expansion of some volume of membrane that is critical for conduction; and (4) react with some specific receptor in the nerve membrane. The first theory fails for lack of evidence that acetylcholine is involved physiologically in conduction. The other three theories, however, all seem to apply.", "contents": "Mechanism of action of local anaesthetic agents and biotoxins. Four current theories for the mechanism of action of local anaesthetics are that these drugs: (1) interfere with some chemical, such as acetylcholine, that is involved in nervous conduction; (2) alter the density of fixed charges on the surface of the membrane; (3) cause an expansion of some volume of membrane that is critical for conduction; and (4) react with some specific receptor in the nerve membrane. The first theory fails for lack of evidence that acetylcholine is involved physiologically in conduction. The other three theories, however, all seem to apply."}
{"id": "PMID:238555", "title": "Plasma concentration of local anaesthetic agents in regard to absorption, distribution and elimination, with special reference to bupivacaine.", "content": "Absorption from the injection site, tissue distribution, metabolism and urinary excretion are the factors determining the plasma concentration of local anaesthetic agents. Other factors such as physico-chemical properties of these drugs may have important influences on these processes. An example of this is the difference in tissue distribution and plasma/erythrocyte ratio as well as an increase in plasma concentration of bupivacaine seen in acidosis. The importance for the plasma concentration, of protein binding, vasoactivity and the effect of depressed circulation are discussed.", "contents": "Plasma concentration of local anaesthetic agents in regard to absorption, distribution and elimination, with special reference to bupivacaine. Absorption from the injection site, tissue distribution, metabolism and urinary excretion are the factors determining the plasma concentration of local anaesthetic agents. Other factors such as physico-chemical properties of these drugs may have important influences on these processes. An example of this is the difference in tissue distribution and plasma/erythrocyte ratio as well as an increase in plasma concentration of bupivacaine seen in acidosis. The importance for the plasma concentration, of protein binding, vasoactivity and the effect of depressed circulation are discussed."}
{"id": "PMID:238556", "title": "Central nervous system effects of local anaesthetic agents.", "content": "A review is given of an experimental study on cats where the influence of acid-base changes on central nervous system toxicity of local anaesthetic agents was studied. The conclusion of this study was that a respiratory acidosis increased the central nervous system toxicity of local anaesthetics and that the underlying metabolic conditions modified this increase. Thus a respiratory acidosis increased this toxicity more if it was based on a metabolic acidosis than on a metabolic alkalosis (Englesson, 1974; Englesson and Grevsten, 1974). An extended analysis is presented where automatic frequency analysis was performed on the e.e.g. recordings performed during the i.v. infusion of lignocaine, bupivacaine, L 134, HS 37 and its optical isomers. The preliminary results show that the electrical changes appearing in the e.e.g. from the start of the i.v. infusion until seizure activity were the same if this time interval was as short as 1 min or as long as 8 min. It also revealed remarkable individual differences between agents, for instance lignocaine displaying marked electrical changes already in the first third of this time period where bupivacaine showed no changes until shortly before seizures.", "contents": "Central nervous system effects of local anaesthetic agents. A review is given of an experimental study on cats where the influence of acid-base changes on central nervous system toxicity of local anaesthetic agents was studied. The conclusion of this study was that a respiratory acidosis increased the central nervous system toxicity of local anaesthetics and that the underlying metabolic conditions modified this increase. Thus a respiratory acidosis increased this toxicity more if it was based on a metabolic acidosis than on a metabolic alkalosis (Englesson, 1974; Englesson and Grevsten, 1974). An extended analysis is presented where automatic frequency analysis was performed on the e.e.g. recordings performed during the i.v. infusion of lignocaine, bupivacaine, L 134, HS 37 and its optical isomers. The preliminary results show that the electrical changes appearing in the e.e.g. from the start of the i.v. infusion until seizure activity were the same if this time interval was as short as 1 min or as long as 8 min. It also revealed remarkable individual differences between agents, for instance lignocaine displaying marked electrical changes already in the first third of this time period where bupivacaine showed no changes until shortly before seizures."}
{"id": "PMID:238557", "title": "The activation of concanavalin A by lanthanide ions.", "content": "Divalent cadmium and lead and the trivalent lanthanides bind in the trasition metal site (S1) of concamavanlin A and induce saccharide binding to the protein in the presence of calcium. Partial activation of the protein in the presence of lanthanides alone indicates these ions bind into both transition metal (S1) and calcium sites (S2). The activity of a lanthanide-protein derivative may be increased by the addition of either calcium or a transition metal ion. The saccharide binding activity decreases in the order Zn2+ is greater than Ni2+ is greater than Co2+ is greater than Mn2+ is greater than Cd2+ reflecting the order of binding constants for these ions in the transition metal site. Like the lanthanides, divalent cadmium substitutes for both the transition metal ion and calcium ion to partially activate the protein. Divalent lead substitutes only for the transition metal ion and partially activates the protein upon addingcalcium. The data are consistent with a model in which saccharide binding activity is independent of the metal size in S1 but critically dependent upon metal size in S2.", "contents": "The activation of concanavalin A by lanthanide ions. Divalent cadmium and lead and the trivalent lanthanides bind in the trasition metal site (S1) of concamavanlin A and induce saccharide binding to the protein in the presence of calcium. Partial activation of the protein in the presence of lanthanides alone indicates these ions bind into both transition metal (S1) and calcium sites (S2). The activity of a lanthanide-protein derivative may be increased by the addition of either calcium or a transition metal ion. The saccharide binding activity decreases in the order Zn2+ is greater than Ni2+ is greater than Co2+ is greater than Mn2+ is greater than Cd2+ reflecting the order of binding constants for these ions in the transition metal site. Like the lanthanides, divalent cadmium substitutes for both the transition metal ion and calcium ion to partially activate the protein. Divalent lead substitutes only for the transition metal ion and partially activates the protein upon addingcalcium. The data are consistent with a model in which saccharide binding activity is independent of the metal size in S1 but critically dependent upon metal size in S2."}
{"id": "PMID:238558", "title": "The mechanism of the bond forming events in pyridine nucleotide linked oxidoreductases. Studies with epoxide inhibitors of lactic dehydrogenase and beta-hydroxybutyrate dehydrogenase.", "content": "2,3-Epoxybutyrate and 2,3-epoxypropionate act as effective competitive inhibitors of pig heart lactic dehydrogenase. KIapp for both inhibitors was pH dependent and varied according to the general equation KIapp = KI(1 +Ka/H+) which may be predicted if the binding of the epoxide to the E-NADH complex involves a compulsory protonation step. Values of KI(epoxybutyrate), KI(epoxypropionate) and pKa were estimated as 150 muM, 860 muM, and 6.8, respectively. The formation of an E-NADH epoxide inhibitor complex was followed directly by fluorescence measurements. Both epoxybutyrate and epoxypropionate enhanced fluorescence of the E-NADH complex and caused a 20-nm blue shift in the maximum emission wavelenght. The dissociation constants measured by fluorescence titration for both epoxides increased as the pH was raised reflecting a decreased affinity for the E-NADH complex. 2,3-Epoxybutyrate was also shown to inhibit beta-hydroxybutyrate dehydrogenase by a mechanism which is consistent with compulsory protonation prior to addition of the epoxide. These results are discussed in terms of a general mechanism for the bond forming events in pyridine nucleotide linked oxidore-ductases.", "contents": "The mechanism of the bond forming events in pyridine nucleotide linked oxidoreductases. Studies with epoxide inhibitors of lactic dehydrogenase and beta-hydroxybutyrate dehydrogenase. 2,3-Epoxybutyrate and 2,3-epoxypropionate act as effective competitive inhibitors of pig heart lactic dehydrogenase. KIapp for both inhibitors was pH dependent and varied according to the general equation KIapp = KI(1 +Ka/H+) which may be predicted if the binding of the epoxide to the E-NADH complex involves a compulsory protonation step. Values of KI(epoxybutyrate), KI(epoxypropionate) and pKa were estimated as 150 muM, 860 muM, and 6.8, respectively. The formation of an E-NADH epoxide inhibitor complex was followed directly by fluorescence measurements. Both epoxybutyrate and epoxypropionate enhanced fluorescence of the E-NADH complex and caused a 20-nm blue shift in the maximum emission wavelenght. The dissociation constants measured by fluorescence titration for both epoxides increased as the pH was raised reflecting a decreased affinity for the E-NADH complex. 2,3-Epoxybutyrate was also shown to inhibit beta-hydroxybutyrate dehydrogenase by a mechanism which is consistent with compulsory protonation prior to addition of the epoxide. These results are discussed in terms of a general mechanism for the bond forming events in pyridine nucleotide linked oxidore-ductases."}
{"id": "PMID:238559", "title": "Zinc and magnesium content of alkaline phosphatase from Escherichia coli.", "content": "Since alkaline phosphatase from Escherichia coli was first reported to contain 2.1 g-atoms of zinc and 0.8 g-aton of magnesium per molecular weight 80,000 (Plocke, D.J., Levinthal, D., and Vallee, B. L. (1962), Biochemistry 1, 373-378), the procedures for isolation and purification of the enzyme, as well as values for the protein molecular weight, specific absorptivity, and maximal activity, have changed repeatedly. Such variations have resulted in uncertainties concerning the molar metal content of this phosphatase. The present paper reviews the initial and recent results of metal analyses of alkaline phosphatase preparations in this laboratory and compares them with those obtained elsewhere, while simultaneously identifying some of the factors which have affected reports on the metal content of this enzyme. A purification procedure is described eliminating the features of all methods known to alter the metal content of phosphatase. In addition, the three isozymic forms, as well as preparations from four E. coli strains commonly employed for phosphatase isolation, were analyzed and compared.", "contents": "Zinc and magnesium content of alkaline phosphatase from Escherichia coli. Since alkaline phosphatase from Escherichia coli was first reported to contain 2.1 g-atoms of zinc and 0.8 g-aton of magnesium per molecular weight 80,000 (Plocke, D.J., Levinthal, D., and Vallee, B. L. (1962), Biochemistry 1, 373-378), the procedures for isolation and purification of the enzyme, as well as values for the protein molecular weight, specific absorptivity, and maximal activity, have changed repeatedly. Such variations have resulted in uncertainties concerning the molar metal content of this phosphatase. The present paper reviews the initial and recent results of metal analyses of alkaline phosphatase preparations in this laboratory and compares them with those obtained elsewhere, while simultaneously identifying some of the factors which have affected reports on the metal content of this enzyme. A purification procedure is described eliminating the features of all methods known to alter the metal content of phosphatase. In addition, the three isozymic forms, as well as preparations from four E. coli strains commonly employed for phosphatase isolation, were analyzed and compared."}
{"id": "PMID:238560", "title": "Structural and catalytic properties of hydrogenase from Chromatium.", "content": "The enzyme hydrogenase, from the photosynthetic bacterium Chromatium, was purified to homogeneity after solubilization of the particulate enzyme with deoxycholate. The purification procedure included ammonium sulfate fractionation, treatment with manganous phosphate gel, heating at 63 degrees, DEAE-cellulose chromatography, and isoelectric focusing. The last step gave two active enzyme fractions with isoelectric points of 4.2 and 4.4. It was shown that the two fractions were different forms of the same protein. The enzyme was obtained in 23% yield and was purified 1700-fold. The enzyme had a molecular weight of 98,000, a sedimentation coefficient of 5.16 S and gave a single protein and activity band on disc gel electrophoresis. Sodium dodecyl sulfate gel electrophoresis gave a single band of mol wt 50,000, suggesting that the active enzyme was composed of two subunits of the same molecular weight. The pure hydrogenase contained four atoms of iron and four atoms of acid-labile sulfide, and had a visible absorption peak at 410 nm. Electron paramagnetic resonance (EPR) spectroscopy at 10--15 K showed a free-radical signal at g' = 2.003 in the oxidized enzyme and signals at g' = 2.2 and 2.06 in the reduced enzyme. These findings suggest that Chromatium hydrogenase is an iron-sulfur protein. The pure hydrogenase catalyzed the exchange reaction between H2 and HDO or HTO, the reduction of Benzyl Viologen and Methylene Blue, and the evolution of hydrogen from reduced Methyl Viologen. The mechanism of hydrogen activation was shown to be heterolytic cleavage to an enzyme hydride and a proton. Hydrogenase could not catalyze reduction of pyridine nucleotides or ferredoxin with H2. The effect of pH and various inhibitors on the enzymatic activity has been studied.", "contents": "Structural and catalytic properties of hydrogenase from Chromatium. The enzyme hydrogenase, from the photosynthetic bacterium Chromatium, was purified to homogeneity after solubilization of the particulate enzyme with deoxycholate. The purification procedure included ammonium sulfate fractionation, treatment with manganous phosphate gel, heating at 63 degrees, DEAE-cellulose chromatography, and isoelectric focusing. The last step gave two active enzyme fractions with isoelectric points of 4.2 and 4.4. It was shown that the two fractions were different forms of the same protein. The enzyme was obtained in 23% yield and was purified 1700-fold. The enzyme had a molecular weight of 98,000, a sedimentation coefficient of 5.16 S and gave a single protein and activity band on disc gel electrophoresis. Sodium dodecyl sulfate gel electrophoresis gave a single band of mol wt 50,000, suggesting that the active enzyme was composed of two subunits of the same molecular weight. The pure hydrogenase contained four atoms of iron and four atoms of acid-labile sulfide, and had a visible absorption peak at 410 nm. Electron paramagnetic resonance (EPR) spectroscopy at 10--15 K showed a free-radical signal at g' = 2.003 in the oxidized enzyme and signals at g' = 2.2 and 2.06 in the reduced enzyme. These findings suggest that Chromatium hydrogenase is an iron-sulfur protein. The pure hydrogenase catalyzed the exchange reaction between H2 and HDO or HTO, the reduction of Benzyl Viologen and Methylene Blue, and the evolution of hydrogen from reduced Methyl Viologen. The mechanism of hydrogen activation was shown to be heterolytic cleavage to an enzyme hydride and a proton. Hydrogenase could not catalyze reduction of pyridine nucleotides or ferredoxin with H2. The effect of pH and various inhibitors on the enzymatic activity has been studied."}
{"id": "PMID:238561", "title": "The interaction of an epoxide with yeast alcohol dehydrogenase: evidence for binding and the modification of two active site cysteines by styrene oxide.", "content": "Yeast alcohol dehydrogenase is inactivated and alkylated by styrene oxide in a single exponential kinetic process. The concentration dependence of half-times for inactivation indicates the formation of an enzyme inhibitor complex, KI = 2.5 times 10(-2) M at pH 8.0. Reduced nicotinamide adenine dinucleotide (NADH), at a concentration of 3 times 10(-4) M where Kd congruent to 1 times 10(-5) M, has a small effect on kinetic parameters for inactivation. Although benzyl alcohol and acetamide-NADH increase the KI for styrene oxide in a manner consistent with their dissociation constants, substrate also increases the rate of inactivation at high styrene oxide concentrations. The reciprocal of half-times for inactivation, extrapolated to infinite styrene oxide concentration, increases with pH between 7.6 and 9.0, pK congruent to 8.5. The stoichiometry of alkylation by [3H]styrene oxide is 2.2 mol of reagent incorporated/mol of subunit, and is accompanied by the loss of 1.9 mol of sulfhydryl/mol of subunit; prior alkylation with iodoacetamide reduces the stoichiometry to 0.88:1, and increases the rate of labeling. Tryptic digests of enzyme modified with [14C]iodoacetamide or [3H]styrene oxide produce two major peptides which cochromatograph, indicating that styrene oxide and iodoacetamide modify the same cysteine residues. Previous investigators have reported that iodoacetate, iodoacetamide, and butyl isocyanate alkylate either of two reactive cysteines of yeast alcohol dehydrogenase; both cysteines cannot be modified simultaneously [Belke et al. (1974), Biochemistry 13, 3418]. The inactivation of enzyme by p-chloromercuribenzoate (PCMB) is reported here to be accompanied by the incorporation of 2.3 mol of PCMB/mol of enzyme subunits, in analogy with styrene oxide; the planarity of the alkylating agent appears to be an important factor in determining the stoichiometry of labeling.", "contents": "The interaction of an epoxide with yeast alcohol dehydrogenase: evidence for binding and the modification of two active site cysteines by styrene oxide. Yeast alcohol dehydrogenase is inactivated and alkylated by styrene oxide in a single exponential kinetic process. The concentration dependence of half-times for inactivation indicates the formation of an enzyme inhibitor complex, KI = 2.5 times 10(-2) M at pH 8.0. Reduced nicotinamide adenine dinucleotide (NADH), at a concentration of 3 times 10(-4) M where Kd congruent to 1 times 10(-5) M, has a small effect on kinetic parameters for inactivation. Although benzyl alcohol and acetamide-NADH increase the KI for styrene oxide in a manner consistent with their dissociation constants, substrate also increases the rate of inactivation at high styrene oxide concentrations. The reciprocal of half-times for inactivation, extrapolated to infinite styrene oxide concentration, increases with pH between 7.6 and 9.0, pK congruent to 8.5. The stoichiometry of alkylation by [3H]styrene oxide is 2.2 mol of reagent incorporated/mol of subunit, and is accompanied by the loss of 1.9 mol of sulfhydryl/mol of subunit; prior alkylation with iodoacetamide reduces the stoichiometry to 0.88:1, and increases the rate of labeling. Tryptic digests of enzyme modified with [14C]iodoacetamide or [3H]styrene oxide produce two major peptides which cochromatograph, indicating that styrene oxide and iodoacetamide modify the same cysteine residues. Previous investigators have reported that iodoacetate, iodoacetamide, and butyl isocyanate alkylate either of two reactive cysteines of yeast alcohol dehydrogenase; both cysteines cannot be modified simultaneously [Belke et al. (1974), Biochemistry 13, 3418]. The inactivation of enzyme by p-chloromercuribenzoate (PCMB) is reported here to be accompanied by the incorporation of 2.3 mol of PCMB/mol of enzyme subunits, in analogy with styrene oxide; the planarity of the alkylating agent appears to be an important factor in determining the stoichiometry of labeling."}
{"id": "PMID:238562", "title": "The two-step reversible denaturation of lactate dehydrogenase at low pH.", "content": "Upon exposure to conditions of low pH, beef B4 lactate dehydrogenase rapidly loses enzymatic activity, but this process can be completely reversed yielding 100% of the original activity if the enzyme is immediately returned to neutral conditions. As the time of exposure to low pH is increased, the fraction of activity recovered declines to a values of 50--60% and remains nearly constant over a period of many hours. Correlated with this behavior is a change in the kinetics of the recovery of activity. Recovery of activity has been shown to be a second-order process for enzyme exposed to low pH for brief periods of time (Anderson, S., and Weber, G. (1966), Arch. Biochem. Biophys. 116, 207). After several minutes at low pH recovery of activity is found to become first order and to occur at a considerably slower rate. Gel filtration chromatography at low pH separates the protein into two fractions. The lower molecular weight fraction is found to be primarily monomeric, as indicated by equilibrium ultracentrifugation, and is capable of recovering enzymatic activity. The higher molecular weight fraction is generated from the lower molecular weight fraction, and is incapable of recovering activity. These results are interpreted to indicate that the enzyme exists sequentially in three denatured forms at low pH, the first two capable of being restored to the native state, and the third irreversibly denatured.", "contents": "The two-step reversible denaturation of lactate dehydrogenase at low pH. Upon exposure to conditions of low pH, beef B4 lactate dehydrogenase rapidly loses enzymatic activity, but this process can be completely reversed yielding 100% of the original activity if the enzyme is immediately returned to neutral conditions. As the time of exposure to low pH is increased, the fraction of activity recovered declines to a values of 50--60% and remains nearly constant over a period of many hours. Correlated with this behavior is a change in the kinetics of the recovery of activity. Recovery of activity has been shown to be a second-order process for enzyme exposed to low pH for brief periods of time (Anderson, S., and Weber, G. (1966), Arch. Biochem. Biophys. 116, 207). After several minutes at low pH recovery of activity is found to become first order and to occur at a considerably slower rate. Gel filtration chromatography at low pH separates the protein into two fractions. The lower molecular weight fraction is found to be primarily monomeric, as indicated by equilibrium ultracentrifugation, and is capable of recovering enzymatic activity. The higher molecular weight fraction is generated from the lower molecular weight fraction, and is incapable of recovering activity. These results are interpreted to indicate that the enzyme exists sequentially in three denatured forms at low pH, the first two capable of being restored to the native state, and the third irreversibly denatured."}
{"id": "PMID:238563", "title": "Substrate activity of structural analogs of isocitrate for isocitrate dehydrogenases from bovine heart.", "content": "D-Garcinia acid (D-threo-1,2-dihydroxy-1,2,3-propanetricarboxylate), like D-isocitrate, has an alpha-DS-hydroxyl group and a beta-LS configuration of the second carboxyl group. The maximal velocity of pyridine nucleotide reduction with D-garcinia acid is 8 and 21% of D-threo-isocitrate with the DPN-linked and TPN-linked isocitrate dehydrogenase from bovine heart, respectively. The other stereoisomers of hydroxycitrate [L-garcinia acid, D- and L-hibiscus acid (D- and L-erythro-1,2-dihydroxy-1,2,3-propanetricarboxylate)] are inactive. DL-threo-Homoisocitrate (DL-threo-1-hydroxy-1,2,4-butanetricarboxylate) supports DPN+ reduction at 10-15% of the rate observed for isocitrate with the DPN-specific enzyme, but is not a substrate for TPN-linked isocitrate dehydrogenase. The values of apparent S0.5 for total isocitrate and total garcinia acid are similar with both enzymes; the apparent S0.5 of total homoisocitrate is two- to threefold higher than that of total isocitrate with the DPN-linked enzyme. Enzymatic oxidative decarboxylation of garcinia acid and homoisocitrate leads to formation of alpha-keto-beta-hydroxyglutarate and alpha-ketoadipate, respectively. DL-Methylmalate (DL-1-hydroxy-2-methylsuccinate) is inactive as a substrate for either dehydrogenase as are the newly synthesized compounds: DL-threo-gamma-isocitrate amide (DL-threo-1-hydroxy-3-carbamy01,2-propanedicarboxylate), beta-methyl-DL-isocitrate (DL-1-hydroxy-2-methyl-1,2,3-propanetricarboxylate), beta-methyl-DL-garcinia acid (DL-threo-1-hydroxyl-2-methoxy-1,2,3-propanetricarboxylate), DL-1-hydroxyl-1,2,2-ethanetricarboxylate, and DL-1,4-dihydroxy-1,2-butanedicarboxylate.", "contents": "Substrate activity of structural analogs of isocitrate for isocitrate dehydrogenases from bovine heart. D-Garcinia acid (D-threo-1,2-dihydroxy-1,2,3-propanetricarboxylate), like D-isocitrate, has an alpha-DS-hydroxyl group and a beta-LS configuration of the second carboxyl group. The maximal velocity of pyridine nucleotide reduction with D-garcinia acid is 8 and 21% of D-threo-isocitrate with the DPN-linked and TPN-linked isocitrate dehydrogenase from bovine heart, respectively. The other stereoisomers of hydroxycitrate [L-garcinia acid, D- and L-hibiscus acid (D- and L-erythro-1,2-dihydroxy-1,2,3-propanetricarboxylate)] are inactive. DL-threo-Homoisocitrate (DL-threo-1-hydroxy-1,2,4-butanetricarboxylate) supports DPN+ reduction at 10-15% of the rate observed for isocitrate with the DPN-specific enzyme, but is not a substrate for TPN-linked isocitrate dehydrogenase. The values of apparent S0.5 for total isocitrate and total garcinia acid are similar with both enzymes; the apparent S0.5 of total homoisocitrate is two- to threefold higher than that of total isocitrate with the DPN-linked enzyme. Enzymatic oxidative decarboxylation of garcinia acid and homoisocitrate leads to formation of alpha-keto-beta-hydroxyglutarate and alpha-ketoadipate, respectively. DL-Methylmalate (DL-1-hydroxy-2-methylsuccinate) is inactive as a substrate for either dehydrogenase as are the newly synthesized compounds: DL-threo-gamma-isocitrate amide (DL-threo-1-hydroxy-3-carbamy01,2-propanedicarboxylate), beta-methyl-DL-isocitrate (DL-1-hydroxy-2-methyl-1,2,3-propanetricarboxylate), beta-methyl-DL-garcinia acid (DL-threo-1-hydroxyl-2-methoxy-1,2,3-propanetricarboxylate), DL-1-hydroxyl-1,2,2-ethanetricarboxylate, and DL-1,4-dihydroxy-1,2-butanedicarboxylate."}
{"id": "PMID:238564", "title": "Purification and characterization of a major endonuclease from rat liver nuclei.", "content": "A major endonuclease has been purified approximately 800-fold from rat liver nuclei using poly(A) as substrate. The enzyme had a molecular weight of about 50,000, and active fractions were obtained which contained no nucleic acid. Enzymatic activity was optimal between pH 6 and 7 and was totally dependent on the presence of a divalent cation. The reaction was inhibited by high ionic strength, polydextran sulfate, heparin, and sodium pyrophosphate. The purified enzyme readily hydrolyzed poly(A), poly(U), poly(C), and denatured DNA, whereas poly(G) was not degraded, and transfer RNA, ribosomal RNA, and native DNA were hydrolyzed only at relatively slow rates. These data suggest that the enzyme may be specific for single-stranded polynucleotides. The purified enzyme was essentially devoid of exonuclease activity, and the products of exhaustive endonuclease digestion of poly(A) were small oligonucleotides terminated with a 5'-phosphoryl group. Evidence was obtained that this endonuclease is localized in the nucleoplasm. Possible functions for this activity are discussed.", "contents": "Purification and characterization of a major endonuclease from rat liver nuclei. A major endonuclease has been purified approximately 800-fold from rat liver nuclei using poly(A) as substrate. The enzyme had a molecular weight of about 50,000, and active fractions were obtained which contained no nucleic acid. Enzymatic activity was optimal between pH 6 and 7 and was totally dependent on the presence of a divalent cation. The reaction was inhibited by high ionic strength, polydextran sulfate, heparin, and sodium pyrophosphate. The purified enzyme readily hydrolyzed poly(A), poly(U), poly(C), and denatured DNA, whereas poly(G) was not degraded, and transfer RNA, ribosomal RNA, and native DNA were hydrolyzed only at relatively slow rates. These data suggest that the enzyme may be specific for single-stranded polynucleotides. The purified enzyme was essentially devoid of exonuclease activity, and the products of exhaustive endonuclease digestion of poly(A) were small oligonucleotides terminated with a 5'-phosphoryl group. Evidence was obtained that this endonuclease is localized in the nucleoplasm. Possible functions for this activity are discussed."}
{"id": "PMID:238565", "title": "Calorimetric and potentiometric characterization of the ionization behavior of ribonuclease A and its complex with 3'-cytosine monophosphate.", "content": "The proton association behavior of ribonuclease A and its complex with 3'-cytosine monophosphate has been thermodynamically characterized in the pH range 4--8 at 25 degrees, mu = 0.05. Calorimetric and potentiometric titration data have been used to estimate the apparent pK values and enthalpy values for protonation of the four histidine residues of the protein, deltaHp. In the free enzyme the pK values were deduced to be 5.0, 5.8, 6.6, and 6.7 and deltaHp deduced to be -6.5, -6.5, -6.5, and -24 kcal/mol for residues 119, 12, 105, and 48, respectively. For the nucleotide-enzyme complex it was concluded that the apparent pK values of residues 119, 12, and 48 increased to an average value of about 7.2, the deltaHp values remaining constant for all histidine groups except 48. It was also concluded that only the dianionic phosphate form  of the nucleotide inhibitor is bound to the enzyme in this pH range. These results are consistent with a thermodynamic model for the binding reaction in which inhibitor-enzyme association is coupled to the ionization of three imidazole residues (12, 119, and 48) and the interaction between the negative phosphate moiety of the inhibitor and the positively charged residues 12 and 119 is purely electrostatic. However, the \"interaction\" with residue 48 probably involves a conformational rearrangement of the macromolecule.", "contents": "Calorimetric and potentiometric characterization of the ionization behavior of ribonuclease A and its complex with 3'-cytosine monophosphate. The proton association behavior of ribonuclease A and its complex with 3'-cytosine monophosphate has been thermodynamically characterized in the pH range 4--8 at 25 degrees, mu = 0.05. Calorimetric and potentiometric titration data have been used to estimate the apparent pK values and enthalpy values for protonation of the four histidine residues of the protein, deltaHp. In the free enzyme the pK values were deduced to be 5.0, 5.8, 6.6, and 6.7 and deltaHp deduced to be -6.5, -6.5, -6.5, and -24 kcal/mol for residues 119, 12, 105, and 48, respectively. For the nucleotide-enzyme complex it was concluded that the apparent pK values of residues 119, 12, and 48 increased to an average value of about 7.2, the deltaHp values remaining constant for all histidine groups except 48. It was also concluded that only the dianionic phosphate form  of the nucleotide inhibitor is bound to the enzyme in this pH range. These results are consistent with a thermodynamic model for the binding reaction in which inhibitor-enzyme association is coupled to the ionization of three imidazole residues (12, 119, and 48) and the interaction between the negative phosphate moiety of the inhibitor and the positively charged residues 12 and 119 is purely electrostatic. However, the \"interaction\" with residue 48 probably involves a conformational rearrangement of the macromolecule."}
{"id": "PMID:238566", "title": "The pH dependence of the thermodynamics of the interaction of 3'-cytidine monophosphate with ribonuclease A.", "content": "The apparent free energy (deltaGapp) and enthalpy changes (deltaHB) associated with the interaction of 3'-cytosine monophosphate (3'-CMP) and ribonuclease A (RNase) are reported for the pH range 4--9, T = 25 degrees, mu = 0.05. The pH dependence of deltaGapp and deltaHB has been interpreted in terms of coupled ionization of histidine residues 12, 48, and 119, assuming that only the dianionic form of the inhibitor is bound. The results of this analysis are consistent with the calorimetric and potentiometric titration results for the free enzyme and its 3'-CMP complex reported in the previous paper (M. Flogel and R. L. Biltonen ((1975), Biochemistry, preceding paper in this issue). This analysis allows the calculation of the thermodynamic quantities associated with hypothetical but clearly defined reactions (e.g., the reaction of the dianionic inhibitor with the completely protonated enzyme). It is concluded that the primary thermodynamic driving forces for the reaction are van der Waals interactions between the riboside moiety and the protein fabric and electrostatic interaction between the negatively charged phosphate group of the inhibitor and the positively charged histidine residues at the binding locus. It is also suggested that the binding reaction is weakly coupled (approximately to 0.5 kcal/mol) with a conformational change of the protein associated with protonation of residue 48. These results are consistent with the model originally proposed by G. G. Hammes ((1968), Adv. Protein Chem. 23, 1) and lend additional quantitative detail to the nature of the reaction.", "contents": "The pH dependence of the thermodynamics of the interaction of 3'-cytidine monophosphate with ribonuclease A. The apparent free energy (deltaGapp) and enthalpy changes (deltaHB) associated with the interaction of 3'-cytosine monophosphate (3'-CMP) and ribonuclease A (RNase) are reported for the pH range 4--9, T = 25 degrees, mu = 0.05. The pH dependence of deltaGapp and deltaHB has been interpreted in terms of coupled ionization of histidine residues 12, 48, and 119, assuming that only the dianionic form of the inhibitor is bound. The results of this analysis are consistent with the calorimetric and potentiometric titration results for the free enzyme and its 3'-CMP complex reported in the previous paper (M. Flogel and R. L. Biltonen ((1975), Biochemistry, preceding paper in this issue). This analysis allows the calculation of the thermodynamic quantities associated with hypothetical but clearly defined reactions (e.g., the reaction of the dianionic inhibitor with the completely protonated enzyme). It is concluded that the primary thermodynamic driving forces for the reaction are van der Waals interactions between the riboside moiety and the protein fabric and electrostatic interaction between the negatively charged phosphate group of the inhibitor and the positively charged histidine residues at the binding locus. It is also suggested that the binding reaction is weakly coupled (approximately to 0.5 kcal/mol) with a conformational change of the protein associated with protonation of residue 48. These results are consistent with the model originally proposed by G. G. Hammes ((1968), Adv. Protein Chem. 23, 1) and lend additional quantitative detail to the nature of the reaction."}
{"id": "PMID:238567", "title": "The magnitude of electrostatic interactions in inhibitor binding and during catalysis by ribonuclease A.", "content": "It is demonstrated that a model of nucleotide binding to ribonuclease A similar to that proposed by Hammes and coworkers (G. G. Hammes (1968), Adv. Protein Chem. 23, 1) is at least, approximately applicable for both cyclic nucleotide substrates and mononucleotide inhibitors at pH values less than or equal to 6.5 and as a function of ionic strength. Calorimetric data on various inhibitors show that the binding reaction can be thermodynamically dissected into a contribution arising from van der Waal's interaction of the nucleoside moiety, characterized by a large negative enthalpy change, and a contribution arising from electrostatic interactions between the negatively charged phosphate group of the inhibitor and the positively charged protein fabric, characterized by a large positive unitary entropy change. Assuming a catalytic mechanism involving the formation of a dianionic pentacoordinated phosphate transition state intermediate, the magnitude of the effect of electrostatic interactions on the overall rate enhancement by the enzyme is estimated to be 2 times 10(2) to 10(6). It is suggested that this effect, along with substrate approximation effects, is sufficient to \"explain\" the catalytic behavior of the enzyme.", "contents": "The magnitude of electrostatic interactions in inhibitor binding and during catalysis by ribonuclease A. It is demonstrated that a model of nucleotide binding to ribonuclease A similar to that proposed by Hammes and coworkers (G. G. Hammes (1968), Adv. Protein Chem. 23, 1) is at least, approximately applicable for both cyclic nucleotide substrates and mononucleotide inhibitors at pH values less than or equal to 6.5 and as a function of ionic strength. Calorimetric data on various inhibitors show that the binding reaction can be thermodynamically dissected into a contribution arising from van der Waal's interaction of the nucleoside moiety, characterized by a large negative enthalpy change, and a contribution arising from electrostatic interactions between the negatively charged phosphate group of the inhibitor and the positively charged protein fabric, characterized by a large positive unitary entropy change. Assuming a catalytic mechanism involving the formation of a dianionic pentacoordinated phosphate transition state intermediate, the magnitude of the effect of electrostatic interactions on the overall rate enhancement by the enzyme is estimated to be 2 times 10(2) to 10(6). It is suggested that this effect, along with substrate approximation effects, is sufficient to \"explain\" the catalytic behavior of the enzyme."}
{"id": "PMID:238568", "title": "Proton nuclear magnetic resonance investigations of fraying in double-stranded d-ApTpGpCpApT in H2O solution.", "content": "The chemical shifts and line widths of the Watson-Crick ring NH resonances of the self-complementary duplex of d-ApTpGpApT have been monitored at low ionic strength and in the presence of Mg ions at neutral pH in aqueous solution to determine the thermodynamic parameters associated with fraying (D. J. Patel (1974), Biochemistry 13, 2396) at the terminal and internal base pairs as a function of temperature and pH. From studies in H2O-MeOH (3:2), the fraying process persists down to approximately -20 degrees for the internal TA base pair and down to and probably beyond -30 degrees for the terminal AT base pair. The observed average chemical shift at each of these base pairs as a function of temperature suggests rapid exchange on the nuclear magnetic resonance (NMR) time scale between helix and coil (chemical shift separation of 3.2 ppm) and have been utilized to determine the dissociation constant at the terminal and internal base pairs. Comparison of the reaction enthalpies elucidated from the chemical shift parameters with those reported from optical studies suggests that the symmetry related internal TA base pairs break in a coupled manner at low ionic strength, with the coupling removed in the presence of Mg ions and high salt. By contrast, the symmetry related terminal AT base pairs break independently of each other in the absence and presence of Mg ions and high salt. The terminal base pair exhibits a Tm of 10-15 degrees lower than that of the internal base pair in the hexanucleotide, with divalent Mg ions and high salt stabilizing the double helix as reflected in the Tm values of these base pairs. The observed line width changes as a function of temperature provide an estimate of the exchange rate of the proton from the coil form with water. The exchange reaction from the coil state is base catalyzed with rate constants in the diffusion limit.", "contents": "Proton nuclear magnetic resonance investigations of fraying in double-stranded d-ApTpGpCpApT in H2O solution. The chemical shifts and line widths of the Watson-Crick ring NH resonances of the self-complementary duplex of d-ApTpGpApT have been monitored at low ionic strength and in the presence of Mg ions at neutral pH in aqueous solution to determine the thermodynamic parameters associated with fraying (D. J. Patel (1974), Biochemistry 13, 2396) at the terminal and internal base pairs as a function of temperature and pH. From studies in H2O-MeOH (3:2), the fraying process persists down to approximately -20 degrees for the internal TA base pair and down to and probably beyond -30 degrees for the terminal AT base pair. The observed average chemical shift at each of these base pairs as a function of temperature suggests rapid exchange on the nuclear magnetic resonance (NMR) time scale between helix and coil (chemical shift separation of 3.2 ppm) and have been utilized to determine the dissociation constant at the terminal and internal base pairs. Comparison of the reaction enthalpies elucidated from the chemical shift parameters with those reported from optical studies suggests that the symmetry related internal TA base pairs break in a coupled manner at low ionic strength, with the coupling removed in the presence of Mg ions and high salt. By contrast, the symmetry related terminal AT base pairs break independently of each other in the absence and presence of Mg ions and high salt. The terminal base pair exhibits a Tm of 10-15 degrees lower than that of the internal base pair in the hexanucleotide, with divalent Mg ions and high salt stabilizing the double helix as reflected in the Tm values of these base pairs. The observed line width changes as a function of temperature provide an estimate of the exchange rate of the proton from the coil form with water. The exchange reaction from the coil state is base catalyzed with rate constants in the diffusion limit."}
{"id": "PMID:238569", "title": "Proton nuclear magnetic resonance investigations of the nucleation and propagation reactions associated with the helix-coil transition of d-ApTpGpCpApT in H2O solution.", "content": "The chemical shifts and line widths of the Watson-Crick ring NH resonances of the self-complementary duplex of d-ApTpGpCpApT have been monitored in the presence of 0.1 M phosphate at neutral pH in aqueous solution. While the resonance positions of the terminal and internal AT base pairs shift upfield and broaden as average resonances with increasing temperature (helix and coil exchange several times prior to exchange with water from the coil form), those of the central GC base pairs broaden in the absence of upfield shifts (exchange with water occurs each time helix converts to coil). The line-width changes at the AT base pairs monitor the lifetime of the coil state at these positions prior to exchange with water while the line-width changes at the GC base pairs monitor the lifetime of the helix prior to dissociation to strands. This permits the separation of the propagation reaction at the AT base pairs from the nucleation reaction at the GC base pairs during helix formation. The experimental data have been quantitatively analyzed to yield (at 20 degrees) a nucleation formation rate of approximately 10(3) sec-1 for the GC base pairs (bimolecular rate constant of approximately 6 times 10(6) l. mol-1 sec-1) and a dissociation rate of 6 times 10(2) sec-1 at these same base pairs (unimolecular dissociation to strands). The unimolecular propagation reactions at the terminal and terminal base pairs are associated with reaction rates greater than 10(4) sec-1. These values are consistent with a slow formation of a stable nucleus at the GC base pairs followed by a rapid propagation reaction at the AT base pairs. The line width of the (GC) central base pairs in the presence of phosphate is a direct measure of the lifetime of the total helix and yields an activation energy of 45 kcal for helix to coil conversion measured over a narrow temperature range. The exchange from the coil form with water is catalyzed by 0.1 M phosphate with a rate constant kHPO2-/4 = 0.2 times 10(6) 1. mol-1 sec-1.", "contents": "Proton nuclear magnetic resonance investigations of the nucleation and propagation reactions associated with the helix-coil transition of d-ApTpGpCpApT in H2O solution. The chemical shifts and line widths of the Watson-Crick ring NH resonances of the self-complementary duplex of d-ApTpGpCpApT have been monitored in the presence of 0.1 M phosphate at neutral pH in aqueous solution. While the resonance positions of the terminal and internal AT base pairs shift upfield and broaden as average resonances with increasing temperature (helix and coil exchange several times prior to exchange with water from the coil form), those of the central GC base pairs broaden in the absence of upfield shifts (exchange with water occurs each time helix converts to coil). The line-width changes at the AT base pairs monitor the lifetime of the coil state at these positions prior to exchange with water while the line-width changes at the GC base pairs monitor the lifetime of the helix prior to dissociation to strands. This permits the separation of the propagation reaction at the AT base pairs from the nucleation reaction at the GC base pairs during helix formation. The experimental data have been quantitatively analyzed to yield (at 20 degrees) a nucleation formation rate of approximately 10(3) sec-1 for the GC base pairs (bimolecular rate constant of approximately 6 times 10(6) l. mol-1 sec-1) and a dissociation rate of 6 times 10(2) sec-1 at these same base pairs (unimolecular dissociation to strands). The unimolecular propagation reactions at the terminal and terminal base pairs are associated with reaction rates greater than 10(4) sec-1. These values are consistent with a slow formation of a stable nucleus at the GC base pairs followed by a rapid propagation reaction at the AT base pairs. The line width of the (GC) central base pairs in the presence of phosphate is a direct measure of the lifetime of the total helix and yields an activation energy of 45 kcal for helix to coil conversion measured over a narrow temperature range. The exchange from the coil form with water is catalyzed by 0.1 M phosphate with a rate constant kHPO2-/4 = 0.2 times 10(6) 1. mol-1 sec-1."}
{"id": "PMID:238570", "title": "Energy dependent hydrogen ion accumulation in submitochondrial particles.", "content": "The fluorescence quenching of 9-aminoacridine (9AA) in suspension of beef heart EDTA submitochondrial particles was studied and was used to calculate the pH gradient between these particles and the medium. This pH gradient, which is energy dependent, is also dependent strongly on the presence of anion species in the medium. It is 2.2 pH units in acetate medium and can be as high as 3.6 units in the presence of other highly lyophilic anions. The anions tested were found to be effective in the following order: SCN- greater than I- greater than NO3- greater than Br- greater than Cl-. The validity of the deltapH calculations was confirmed by comparison with deltapH values calculated from NH4+ uptake. In contrast, calculations based on quinacrine (QA) fluorescence quenching under the same assumption used for 9AA did not agree with NH4+ measurements and show quantitative and in some cases even qualitative differences. Both carbonyl cyanide p-trifluoromethoxyphenylhydrazone and NH4+ decreased deltapH significantly. When the rate of electron transport is slow, i.e., with succinate as substrate or with NADH and low concentration of rotenone, very low concentration of nigericin (less than 20 ng/ml) decreased deltapH. Under these conditions, valinomycin antagonized the nigericin effect and restored deltapH to its original value. Upon increasing nigericin concentration (greater than 100 ng/ml) the valinomycin effect is gradually replaced by a slower response of further reduction of deltapH.", "contents": "Energy dependent hydrogen ion accumulation in submitochondrial particles. The fluorescence quenching of 9-aminoacridine (9AA) in suspension of beef heart EDTA submitochondrial particles was studied and was used to calculate the pH gradient between these particles and the medium. This pH gradient, which is energy dependent, is also dependent strongly on the presence of anion species in the medium. It is 2.2 pH units in acetate medium and can be as high as 3.6 units in the presence of other highly lyophilic anions. The anions tested were found to be effective in the following order: SCN- greater than I- greater than NO3- greater than Br- greater than Cl-. The validity of the deltapH calculations was confirmed by comparison with deltapH values calculated from NH4+ uptake. In contrast, calculations based on quinacrine (QA) fluorescence quenching under the same assumption used for 9AA did not agree with NH4+ measurements and show quantitative and in some cases even qualitative differences. Both carbonyl cyanide p-trifluoromethoxyphenylhydrazone and NH4+ decreased deltapH significantly. When the rate of electron transport is slow, i.e., with succinate as substrate or with NADH and low concentration of rotenone, very low concentration of nigericin (less than 20 ng/ml) decreased deltapH. Under these conditions, valinomycin antagonized the nigericin effect and restored deltapH to its original value. Upon increasing nigericin concentration (greater than 100 ng/ml) the valinomycin effect is gradually replaced by a slower response of further reduction of deltapH."}
{"id": "PMID:238571", "title": "Nonenzymatic acetylation of histones with acetyl phosphate and acetyl adenylate.", "content": "Nonenzymatic acetylation of calf-thymus lysine- and arginine-rich histones was demonstrated to occur when these proteins were incubated with [14C]acetyl phosphate and [14C]acetyl adenylate. The levels of acetylation depend on both pH and on reagent concentration. When acetyl [33P]phosphate and acetyl [3H]adenylate were used as reagents, we found neither histone phosphorylation nor adenylylation. Most of the radioactivity of 14C-labeled acetylated histones was recovered as Ne-acetyllysine. Furthermore, only a small amount of O-bound radioactivity was released by the 14C-labeled acetylated arginine-rich histone during treatment with hydroxylamine. Experiments on the acetylation of histones, in the presence of increasing salt concentration, gave different results for the two acetylating agents.", "contents": "Nonenzymatic acetylation of histones with acetyl phosphate and acetyl adenylate. Nonenzymatic acetylation of calf-thymus lysine- and arginine-rich histones was demonstrated to occur when these proteins were incubated with [14C]acetyl phosphate and [14C]acetyl adenylate. The levels of acetylation depend on both pH and on reagent concentration. When acetyl [33P]phosphate and acetyl [3H]adenylate were used as reagents, we found neither histone phosphorylation nor adenylylation. Most of the radioactivity of 14C-labeled acetylated histones was recovered as Ne-acetyllysine. Furthermore, only a small amount of O-bound radioactivity was released by the 14C-labeled acetylated arginine-rich histone during treatment with hydroxylamine. Experiments on the acetylation of histones, in the presence of increasing salt concentration, gave different results for the two acetylating agents."}
{"id": "PMID:238572", "title": "The binding of azide to human methemoglobin A0. Error analysis for the interpolative and noninterpolative methods.", "content": "The binding azide to human methemoglobin A0 has been studied at 6 degrees, pH 7, and I = 0.2 by three spectroscopic methods: (1) the conventional interpolative method, (2) an interpolative dialysis technique, and (3) a noninterpolative method. The interpolative methods assume that the fractional spectral change equals the fraction of heme sites bound by ligand, while the noninterpolative method measures the extent of binding directly, i.e., without the interpolative assumption. Both experiment and error analysis show that method 1 has low precision, and consequently, gives an inherently unreliable binding isotherm. Method 2 achieves high experimental and intrinsic precision. However, method 3, which also has high precision, clearly proves that the interpolative assumption of method 2 is incorrect. That is, the true fractional extent of binding becomes equal to the fractional spectral change only after about 97% of heme sites have been bound with ligands.", "contents": "The binding of azide to human methemoglobin A0. Error analysis for the interpolative and noninterpolative methods. The binding azide to human methemoglobin A0 has been studied at 6 degrees, pH 7, and I = 0.2 by three spectroscopic methods: (1) the conventional interpolative method, (2) an interpolative dialysis technique, and (3) a noninterpolative method. The interpolative methods assume that the fractional spectral change equals the fraction of heme sites bound by ligand, while the noninterpolative method measures the extent of binding directly, i.e., without the interpolative assumption. Both experiment and error analysis show that method 1 has low precision, and consequently, gives an inherently unreliable binding isotherm. Method 2 achieves high experimental and intrinsic precision. However, method 3, which also has high precision, clearly proves that the interpolative assumption of method 2 is incorrect. That is, the true fractional extent of binding becomes equal to the fractional spectral change only after about 97% of heme sites have been bound with ligands."}
{"id": "PMID:238573", "title": "Hydrogen-deuterium exchange in nucleosides and nucleotides. A mechanism for exchange of the exocyclic amino hydrogens of adenosine.", "content": "The pH dependence of the apparent first-order rate constant for the exchange of the exocyclic amino hydrogens of adenosine with deuterium from the solvent was measured by stopped-flow ultraviolet spectroscopy. This dependence shows acid catalysis, base catalysis, and spontaneous exchange at neutral pH values. A study of the effect of several buffers on the rates of exchange reveals both general acid and general base catalytic behavior for the exchange process. We propose a general mechanism for the exchange which requires N-1 protonated adenosine as an intermediate for the acid-catalyzed exchange and amidine anion for the base-catalyzed exchange. In both cases the rate-limiting step is the base-catalyzed abstraction of a proton from the exocyclic amino moiety. Evaluation of the rate constants predicts the equilibrium for the exocyclic amino/imino tautomers to be 6.3 times 10(3):1.", "contents": "Hydrogen-deuterium exchange in nucleosides and nucleotides. A mechanism for exchange of the exocyclic amino hydrogens of adenosine. The pH dependence of the apparent first-order rate constant for the exchange of the exocyclic amino hydrogens of adenosine with deuterium from the solvent was measured by stopped-flow ultraviolet spectroscopy. This dependence shows acid catalysis, base catalysis, and spontaneous exchange at neutral pH values. A study of the effect of several buffers on the rates of exchange reveals both general acid and general base catalytic behavior for the exchange process. We propose a general mechanism for the exchange which requires N-1 protonated adenosine as an intermediate for the acid-catalyzed exchange and amidine anion for the base-catalyzed exchange. In both cases the rate-limiting step is the base-catalyzed abstraction of a proton from the exocyclic amino moiety. Evaluation of the rate constants predicts the equilibrium for the exocyclic amino/imino tautomers to be 6.3 times 10(3):1."}
{"id": "PMID:238574", "title": "Effects of an acetyl-coenzyme A carboxylase inhibitor and a sodium-sparing diuretic on aldosterone-stimulated sodium transport, lipid synthesis, and phospholipid fatty acid composition in the toad urinary bladder.", "content": "A correlation study of the effects of two agents, 2-methyl-2-[p-(1,2,3,4-tetrahydro-1-naphthyl)phenoxy]propionic acid (TPIA) and amiloride, on aldosterone-induced alterations in Na+ transport, lipid synthesis, and phospholipid fatty acid composition has been carried out in the toad urinary bladder. TPIA, an inhibitor of acetyl-CoA carboxylase, inhibits aldosterone-stimulated Na+ transport as well as hormone-induced lipid synthesis and the increase in weight percentage of phospholipid long-chain polyunsaturated fatty acids. Amiloride, a diuretic which blocks sodium entry into the transporting epithelium, does not alter aldosterone's effects on lipid and fatty acid metabolism but prevents the hormone-induced increase in Na+ transport. These results support the conclusion that aldosterone increases Na+ transport in the toad urinary bladder by altering membrane fatty acid metabolism and that the lipid biosynthetic events following aldosterone treatment are a primary response to the hormone and not secondary to increased Na+ transport.", "contents": "Effects of an acetyl-coenzyme A carboxylase inhibitor and a sodium-sparing diuretic on aldosterone-stimulated sodium transport, lipid synthesis, and phospholipid fatty acid composition in the toad urinary bladder. A correlation study of the effects of two agents, 2-methyl-2-[p-(1,2,3,4-tetrahydro-1-naphthyl)phenoxy]propionic acid (TPIA) and amiloride, on aldosterone-induced alterations in Na+ transport, lipid synthesis, and phospholipid fatty acid composition has been carried out in the toad urinary bladder. TPIA, an inhibitor of acetyl-CoA carboxylase, inhibits aldosterone-stimulated Na+ transport as well as hormone-induced lipid synthesis and the increase in weight percentage of phospholipid long-chain polyunsaturated fatty acids. Amiloride, a diuretic which blocks sodium entry into the transporting epithelium, does not alter aldosterone's effects on lipid and fatty acid metabolism but prevents the hormone-induced increase in Na+ transport. These results support the conclusion that aldosterone increases Na+ transport in the toad urinary bladder by altering membrane fatty acid metabolism and that the lipid biosynthetic events following aldosterone treatment are a primary response to the hormone and not secondary to increased Na+ transport."}
{"id": "PMID:238575", "title": "Equilibrium measurements of cognate and noncognate interactions between aminoacyl transfer RNA synthetases and transfer RNA.", "content": "The interaction of Escherichia coli isoleucyl-tRNA synthetase with its cognate and five noncognate tRNAs, and of yeast valyl-tRNA synthetase with its cognate and four noncognate tRNAs, has been measured directly by fluorescence quenching. The cognate associations are strongest (association constant of 10(8) M-1 or more at pH 5.5, 17 degrees). A wide variation is found in the strengths of the noncognate interactions; these have association constants smaller than that of these cognate association by a factor of less than 10 to over 10(4), depending on the enzyme-t-RNA pair. A more detailed study of the cognate isoleucyl-tRNA synthetase-tRNAIle association suggests that the strength of the interaction is markedly sensitive to a pH-dependent transition in the enzyme centered at pH 6 on the other hand, Mg2+-induced structural changes in tRNAIle at 17 degrees in low salt do not greatly affect the availability of the nucleic acid's receptor sites for enzyme...", "contents": "Equilibrium measurements of cognate and noncognate interactions between aminoacyl transfer RNA synthetases and transfer RNA. The interaction of Escherichia coli isoleucyl-tRNA synthetase with its cognate and five noncognate tRNAs, and of yeast valyl-tRNA synthetase with its cognate and four noncognate tRNAs, has been measured directly by fluorescence quenching. The cognate associations are strongest (association constant of 10(8) M-1 or more at pH 5.5, 17 degrees). A wide variation is found in the strengths of the noncognate interactions; these have association constants smaller than that of these cognate association by a factor of less than 10 to over 10(4), depending on the enzyme-t-RNA pair. A more detailed study of the cognate isoleucyl-tRNA synthetase-tRNAIle association suggests that the strength of the interaction is markedly sensitive to a pH-dependent transition in the enzyme centered at pH 6 on the other hand, Mg2+-induced structural changes in tRNAIle at 17 degrees in low salt do not greatly affect the availability of the nucleic acid's receptor sites for enzyme..."}
{"id": "PMID:238576", "title": "A 13C nuclear magnetic resonance and circular dichroism study of the collagen-gelatin transformation in enzyme solubilized collagen.", "content": "Natural abundance Fourier transform 13C nuclear magnetic resonance (13C NMR) were obtained for enzyme solubilized collagen at 1 degrees intervals through the transition region. The transition of collagen molecules from the rigid triple helical state to single-stranded, random-coil state is accompanied by a change from broadened carbon resonances unobservable under high-resolution conditions to narrow line spectra. Thus distinction can be made between helical and random-coil states of individual residues. The transition is monophasic, as determined by examination of 14 different carbon resonances, and the entire structure is found to melt cooperatively over a temperature interval of 5 +/- 1 degrees. All the residues seem to be involved in the unfolding process concurrently. The transition was also studied by examining the changes in the circular dichroism spectrum brought about by heating. The experiments corroborated the observation that the transition proceeded cooperatively over a temperature interval of 4 degrees. Enzyme soluble collagen is seen to melt less cooperatively than native collagen. The enthalpy change was determined by assuming an equilibrium between three random coil gelatin chains and tropocollogen molecules. From the enthalpy, the average length of the tripeptide sequences (70-85) involved in the transition can be estimated. The shortening of the cooperative unit could arise as a result of some alteration of the native conformation through proctase treatment.", "contents": "A 13C nuclear magnetic resonance and circular dichroism study of the collagen-gelatin transformation in enzyme solubilized collagen. Natural abundance Fourier transform 13C nuclear magnetic resonance (13C NMR) were obtained for enzyme solubilized collagen at 1 degrees intervals through the transition region. The transition of collagen molecules from the rigid triple helical state to single-stranded, random-coil state is accompanied by a change from broadened carbon resonances unobservable under high-resolution conditions to narrow line spectra. Thus distinction can be made between helical and random-coil states of individual residues. The transition is monophasic, as determined by examination of 14 different carbon resonances, and the entire structure is found to melt cooperatively over a temperature interval of 5 +/- 1 degrees. All the residues seem to be involved in the unfolding process concurrently. The transition was also studied by examining the changes in the circular dichroism spectrum brought about by heating. The experiments corroborated the observation that the transition proceeded cooperatively over a temperature interval of 4 degrees. Enzyme soluble collagen is seen to melt less cooperatively than native collagen. The enthalpy change was determined by assuming an equilibrium between three random coil gelatin chains and tropocollogen molecules. From the enthalpy, the average length of the tripeptide sequences (70-85) involved in the transition can be estimated. The shortening of the cooperative unit could arise as a result of some alteration of the native conformation through proctase treatment."}
{"id": "PMID:238577", "title": "Nonspecific acid phosphatase from Schizosaccharomyces pombe. Purification and physical chemical properties.", "content": "Repressible nonspecific acid phosphatase from Schizosaccharomyces pombe was purified to apparent homogeneity, as ascertained from ultracentrifugal, electrophoretic, and chromatographic data. The native protein has a molecular weight of 383,000 as determined by sucrose density gradient centrifugation and 381,000 as determined by gel filtration. The native protein can be dissociated in the presence of 8 M urea-1% sodium dodecyl sulfate into sub-units possessing an approximate molecular weight of 104,000. Neutral sugars account for about 66% of the total molecular weight and contribute to the high solubility and some of the other physical properties of this enzyme. Purified enzyme preparations have a Km for 4-nitrophenyl phosphate of 0.17 mM and a broad substrate specificity, but do not show diesterase activity. Phosphate and sulfate are competitive inhibitors. The enzyme is inactivated at neutral and alkaline pH and at relatively low temperatures. Mannose and galactose was found as the main components of the carbohydrate moiety; glucosamine was present in lower amounts. The amino acid analysis revealed a high content of aspartate, threonine, and serine; no sulfhydryl group could be detected. Pi is released in stoichiometric amount (1 mol per enzyme monomer) on protein digestion.", "contents": "Nonspecific acid phosphatase from Schizosaccharomyces pombe. Purification and physical chemical properties. Repressible nonspecific acid phosphatase from Schizosaccharomyces pombe was purified to apparent homogeneity, as ascertained from ultracentrifugal, electrophoretic, and chromatographic data. The native protein has a molecular weight of 383,000 as determined by sucrose density gradient centrifugation and 381,000 as determined by gel filtration. The native protein can be dissociated in the presence of 8 M urea-1% sodium dodecyl sulfate into sub-units possessing an approximate molecular weight of 104,000. Neutral sugars account for about 66% of the total molecular weight and contribute to the high solubility and some of the other physical properties of this enzyme. Purified enzyme preparations have a Km for 4-nitrophenyl phosphate of 0.17 mM and a broad substrate specificity, but do not show diesterase activity. Phosphate and sulfate are competitive inhibitors. The enzyme is inactivated at neutral and alkaline pH and at relatively low temperatures. Mannose and galactose was found as the main components of the carbohydrate moiety; glucosamine was present in lower amounts. The amino acid analysis revealed a high content of aspartate, threonine, and serine; no sulfhydryl group could be detected. Pi is released in stoichiometric amount (1 mol per enzyme monomer) on protein digestion."}
{"id": "PMID:238578", "title": "Comparison of glucocorticoid-binding proteins in normal and neoplastic mammary tissues of the rat.", "content": "Kinetic and molecular properties of components binding [3H]triamcinolone acetonide were studied using 105,000g supernatants of lactating mammary gland, R3230AC, and dimethylbenz[a]anthracene (DMBA) induced mammary tumors of the rat. Using a dextran-coated charcoal adsorption procedure, the relationship between specific glucocorticoid binding and protein concentration was linear in the range of 0.5-4.0 mg/reaction. These cytoplasmic macromolecules bound [3H]triamcinolone acetonide with limited capacity (50-400 fmol/mg of cytosol protein) and high affinity, Kd approximately 10(-8)-10(-9) M. Optimal binding was obtained when homogenizations were made in Tris buffers, at pH 7.4, containing monothioglycerol. Time course of association of [3H]triamcinolone acetonide and its binding sites showed maximal binding by 6-8 hr at 3 degrees which remained unchanged up to 24 hr. The rate constant of association at 3 degrees was in the range of 2-4 x 10(5) M-1 min-1. The rate constant of dissociation of bound [3H]triamcinolone acetonide could not be calculated accurately since the reaction was essentially irreversible for 5 hr at 3 degrees. Estimation of the half-life of the steroid-binding protein complexes from the Kd and the rate constant for association gave a value of 11-12 hr. From ligand specificity studies, the glucocorticoids, triamcinolone acetonide, corticosterone, cortisol, and dexamethasone competed well for [3H]triamcinolone acetonide binding sites. Progesterone, aldosterone, and the anti-glucocorticoid, cortexolone, were also good competitors while androgens and estrogens were weak inhibitors of binding. The binding compenents sedimented at 7-8 S in sucrose gradients of low ionic strength and dissociated into lower molecular weight components sedimenting at 4-5S in high ionic strength gradients. Studies in vivo using animals bearing the DMBA-induced tumor demonstrated that [3H]triamcinolone acetonide binding complexes were present in cytoplasmic and nuclear compartments. Sedimentation coefficients of the cytoplasmic and nuclear forms of these receptors labeled in vivo were 7-8S and 4-5S, respectively. These studies suggest that the molecular and kinetic binding properties of glucocorticoid receptors in neoplastic mammary tissues are similar to those of the normal mammary gland.", "contents": "Comparison of glucocorticoid-binding proteins in normal and neoplastic mammary tissues of the rat. Kinetic and molecular properties of components binding [3H]triamcinolone acetonide were studied using 105,000g supernatants of lactating mammary gland, R3230AC, and dimethylbenz[a]anthracene (DMBA) induced mammary tumors of the rat. Using a dextran-coated charcoal adsorption procedure, the relationship between specific glucocorticoid binding and protein concentration was linear in the range of 0.5-4.0 mg/reaction. These cytoplasmic macromolecules bound [3H]triamcinolone acetonide with limited capacity (50-400 fmol/mg of cytosol protein) and high affinity, Kd approximately 10(-8)-10(-9) M. Optimal binding was obtained when homogenizations were made in Tris buffers, at pH 7.4, containing monothioglycerol. Time course of association of [3H]triamcinolone acetonide and its binding sites showed maximal binding by 6-8 hr at 3 degrees which remained unchanged up to 24 hr. The rate constant of association at 3 degrees was in the range of 2-4 x 10(5) M-1 min-1. The rate constant of dissociation of bound [3H]triamcinolone acetonide could not be calculated accurately since the reaction was essentially irreversible for 5 hr at 3 degrees. Estimation of the half-life of the steroid-binding protein complexes from the Kd and the rate constant for association gave a value of 11-12 hr. From ligand specificity studies, the glucocorticoids, triamcinolone acetonide, corticosterone, cortisol, and dexamethasone competed well for [3H]triamcinolone acetonide binding sites. Progesterone, aldosterone, and the anti-glucocorticoid, cortexolone, were also good competitors while androgens and estrogens were weak inhibitors of binding. The binding compenents sedimented at 7-8 S in sucrose gradients of low ionic strength and dissociated into lower molecular weight components sedimenting at 4-5S in high ionic strength gradients. Studies in vivo using animals bearing the DMBA-induced tumor demonstrated that [3H]triamcinolone acetonide binding complexes were present in cytoplasmic and nuclear compartments. Sedimentation coefficients of the cytoplasmic and nuclear forms of these receptors labeled in vivo were 7-8S and 4-5S, respectively. These studies suggest that the molecular and kinetic binding properties of glucocorticoid receptors in neoplastic mammary tissues are similar to those of the normal mammary gland."}
{"id": "PMID:238579", "title": "Heavy metal-nucleoside interactions. Binding of methylmercury(II) to inosine and catalysis of the isotopic exchange of the C-8 hydrogen studied by 1-H nuclear magnetic resonance and raman difference spectrophotometry.", "content": "Raman difference spectrophotometry reveals that CH3HgII binds quantitatively to N(1) of inosine at pH 8, substituting for the proton. When N(1) is saturated, binding occurs at a second site. Measurements of the 1-H nuclear magnetic resonance spectra of both inosine and of CH3Hg-II are in agreement with the N(1) binding and indicate that the second site for mercuriation is N(7). This second binding reaction is observed to increase the rate of exchange of the C(8) hydrogen with solvent, consistent with results observed for alkylation at N(7). Coordination of the electrophilic CH3Hg-II to N(7) increases the acidity of H(8), facilitating OHminus--catalyzed proton abstraction and reprotonation by themedium. For comparison, the reaction of CH3Hg-II with [8-2-H]inosine has been studied. Displacement of the N(1) hydrogen upon mercuriation of inosine causes a significant electron delocalization into the ring, increasing the basicity of N(7), and accounting for the synergic effect in metal binding observed originally by Simpson. In contrast, 1-methylinosine interacts only slightly with CH3Hg-II at pH 8. Coordination appears to be at N(7), since H(8) again is observed to exchange rapidly with solvent protons. In acidic solution, pH less than 2, binding to inosine is almost quantitative and exclusively to N(7). The behavior of CH3Hg-II is compared with that of Pt(II) and with Ni(II), Co(II), AND Zn(II). A brief comparison is made among ultraviolet absorption spectrophotometry, nuclear magnetic resonance (NMR), and Raman difference spectrophotometry for studying reactions of nucleosides and nucleotides.", "contents": "Heavy metal-nucleoside interactions. Binding of methylmercury(II) to inosine and catalysis of the isotopic exchange of the C-8 hydrogen studied by 1-H nuclear magnetic resonance and raman difference spectrophotometry. Raman difference spectrophotometry reveals that CH3HgII binds quantitatively to N(1) of inosine at pH 8, substituting for the proton. When N(1) is saturated, binding occurs at a second site. Measurements of the 1-H nuclear magnetic resonance spectra of both inosine and of CH3Hg-II are in agreement with the N(1) binding and indicate that the second site for mercuriation is N(7). This second binding reaction is observed to increase the rate of exchange of the C(8) hydrogen with solvent, consistent with results observed for alkylation at N(7). Coordination of the electrophilic CH3Hg-II to N(7) increases the acidity of H(8), facilitating OHminus--catalyzed proton abstraction and reprotonation by themedium. For comparison, the reaction of CH3Hg-II with [8-2-H]inosine has been studied. Displacement of the N(1) hydrogen upon mercuriation of inosine causes a significant electron delocalization into the ring, increasing the basicity of N(7), and accounting for the synergic effect in metal binding observed originally by Simpson. In contrast, 1-methylinosine interacts only slightly with CH3Hg-II at pH 8. Coordination appears to be at N(7), since H(8) again is observed to exchange rapidly with solvent protons. In acidic solution, pH less than 2, binding to inosine is almost quantitative and exclusively to N(7). The behavior of CH3Hg-II is compared with that of Pt(II) and with Ni(II), Co(II), AND Zn(II). A brief comparison is made among ultraviolet absorption spectrophotometry, nuclear magnetic resonance (NMR), and Raman difference spectrophotometry for studying reactions of nucleosides and nucleotides."}
{"id": "PMID:238580", "title": "Ionic and nucleotide requirements for microtubule polymerization in vitro.", "content": "The ionic and nucleotide requirements for the in vitro polymerization of microtubules from purified brain tubulin have been characterized by viscometry. Protein was purified by successive cycles of a temperature dependent assembly-diassembly scheme. Maximal polymerization occurred at a concentration of 0.1 M Pipes (piperazine-N,N'-bis(2-ethanesulfonic acid)); increasing ionic strength by addition of NaCl to samples prepared in lower buffer concentrations did not result in an equivalent level of polymerization. Both Na-+ and K-+ inhibited microtubule formation at levels greater than 240 mM, withmaximal assembly occurring at physiological concentrations of 150 mM. Maximal extent of assembly occurred at pH 6.8 and optimal rate at pH 6.6. Inhibition of polymerization was half-maximal at added calcium concentrations of 1.0 mM and magnesium concentrations of 10.0 mM. EGTA (ethylene glycol bis(beta-aminoethyl ether)tetraacetic acid), which chelates Ca-2+, had no effect on polymerization over a concentration range of 0.01-10.0 mM. In contrast, EDTA (ethylenediaminetetraacetic acid), which chelates both Mg-2+ and Ca-2+, inhibited assemble half-maximally at 0.25 mM and totally at 2.0 mM. As determined from experiments using Mg-2+-EDTA buffers, magnesium was required for polymerization. Magnesium promoted the maximal extent of assembly at substoichiometric levels relative to tubulin, but was maximal for both rate and extent at stoichiometric concentrations. Elemental analyses indicated that approximately 1 mol of magnesium was tightly bound/mol of tubulin dimer. Viscosity development was dependent upon hydrolyzable nucleoside triphosphate, and stoichiometric levels of GTP were sufficient for maximal polymerization. The effect of magnesium in increasing the rate of GTP-dependent polymerization suggests that a Mg-2+-GTP complex is the substrate required for a step in assembly.", "contents": "Ionic and nucleotide requirements for microtubule polymerization in vitro. The ionic and nucleotide requirements for the in vitro polymerization of microtubules from purified brain tubulin have been characterized by viscometry. Protein was purified by successive cycles of a temperature dependent assembly-diassembly scheme. Maximal polymerization occurred at a concentration of 0.1 M Pipes (piperazine-N,N'-bis(2-ethanesulfonic acid)); increasing ionic strength by addition of NaCl to samples prepared in lower buffer concentrations did not result in an equivalent level of polymerization. Both Na-+ and K-+ inhibited microtubule formation at levels greater than 240 mM, withmaximal assembly occurring at physiological concentrations of 150 mM. Maximal extent of assembly occurred at pH 6.8 and optimal rate at pH 6.6. Inhibition of polymerization was half-maximal at added calcium concentrations of 1.0 mM and magnesium concentrations of 10.0 mM. EGTA (ethylene glycol bis(beta-aminoethyl ether)tetraacetic acid), which chelates Ca-2+, had no effect on polymerization over a concentration range of 0.01-10.0 mM. In contrast, EDTA (ethylenediaminetetraacetic acid), which chelates both Mg-2+ and Ca-2+, inhibited assemble half-maximally at 0.25 mM and totally at 2.0 mM. As determined from experiments using Mg-2+-EDTA buffers, magnesium was required for polymerization. Magnesium promoted the maximal extent of assembly at substoichiometric levels relative to tubulin, but was maximal for both rate and extent at stoichiometric concentrations. Elemental analyses indicated that approximately 1 mol of magnesium was tightly bound/mol of tubulin dimer. Viscosity development was dependent upon hydrolyzable nucleoside triphosphate, and stoichiometric levels of GTP were sufficient for maximal polymerization. The effect of magnesium in increasing the rate of GTP-dependent polymerization suggests that a Mg-2+-GTP complex is the substrate required for a step in assembly."}
{"id": "PMID:238581", "title": "Reactions of fluorescent probes with normal and chemically modified myelin.", "content": "The fluorescent probes 8-anilino-1-naphthalenesulfonate (ANS) and 2-p-toluidinylnaphthalene-6-sulfonate (TNS) bind to highly purified myelin membranes obtained from bovine brain white matter. Binding of the dyes was markedly increased by environmental conditions which reduce the negative surface potential of the membrane, i.e., cations (La-3+ is greater than Ca-2+ is greater than Na-+,K-+), H-+, local anesthetics, and the antibiotic polymyxin B. Chemical alteration of accessible membrane charged groups affected dye binding in a manner consistent with the hypothesis that such binding is primarily dependent upon the membrane surface potential. Thus, binding was increased by blocking of carboxyl groups via carbodiimide activation and subsequent coupling with neutral amino acid esters, and even more so with a basic amino acid ester (e.g., arginine methyl ester). Dye binding was reduced by succinylation of amino groups, and by hydrolysis of choline and ethanolamine head groups of phospho- and sphingolipids by phospholipase C. Phospholipase C treatment of myelin, or sphingomyelin vesicles, reduced or abolished the augmentation of ANS and TNS binding due to cations, local anesthetics, or polymyxin B. Energy transfer from myelin tryptophan residues to bound ANS occurs, but with low efficiency. Oxidation of membrane tryptophan residues with N-bromosuccinimide, or alkylation with 2-hydroxy (or methoxy)-5-nitrobenzyl bromide, markedly reduced intrinsic membrane fluorescence and energy transfer to bound ANS, but did not significantly affect dye binding or the quantum yield of ANS fluorescence when excitation was at 380nm. Proteolytic digestion removed 6-30% of myelin protein, depending upon the enzyme used, but had no effect on fluorescent dye binding. It is concluded that the binding of the anionic fluorescent probes ANS and TNS to myelin is primarily a function of the membrane surface charge density and net surface potential, as is the case with other biological membranes. Conclusions about the degree of dye binding to membrane lipids or membrane proteins cannot be drawn unless additional studies are carried out on isolated water soluble membrane proteins.", "contents": "Reactions of fluorescent probes with normal and chemically modified myelin. The fluorescent probes 8-anilino-1-naphthalenesulfonate (ANS) and 2-p-toluidinylnaphthalene-6-sulfonate (TNS) bind to highly purified myelin membranes obtained from bovine brain white matter. Binding of the dyes was markedly increased by environmental conditions which reduce the negative surface potential of the membrane, i.e., cations (La-3+ is greater than Ca-2+ is greater than Na-+,K-+), H-+, local anesthetics, and the antibiotic polymyxin B. Chemical alteration of accessible membrane charged groups affected dye binding in a manner consistent with the hypothesis that such binding is primarily dependent upon the membrane surface potential. Thus, binding was increased by blocking of carboxyl groups via carbodiimide activation and subsequent coupling with neutral amino acid esters, and even more so with a basic amino acid ester (e.g., arginine methyl ester). Dye binding was reduced by succinylation of amino groups, and by hydrolysis of choline and ethanolamine head groups of phospho- and sphingolipids by phospholipase C. Phospholipase C treatment of myelin, or sphingomyelin vesicles, reduced or abolished the augmentation of ANS and TNS binding due to cations, local anesthetics, or polymyxin B. Energy transfer from myelin tryptophan residues to bound ANS occurs, but with low efficiency. Oxidation of membrane tryptophan residues with N-bromosuccinimide, or alkylation with 2-hydroxy (or methoxy)-5-nitrobenzyl bromide, markedly reduced intrinsic membrane fluorescence and energy transfer to bound ANS, but did not significantly affect dye binding or the quantum yield of ANS fluorescence when excitation was at 380nm. Proteolytic digestion removed 6-30% of myelin protein, depending upon the enzyme used, but had no effect on fluorescent dye binding. It is concluded that the binding of the anionic fluorescent probes ANS and TNS to myelin is primarily a function of the membrane surface charge density and net surface potential, as is the case with other biological membranes. Conclusions about the degree of dye binding to membrane lipids or membrane proteins cannot be drawn unless additional studies are carried out on isolated water soluble membrane proteins."}
{"id": "PMID:238582", "title": "Circular dichroism and gel filtration behavior of subtilisin enzymes in concentrated solutions of guanidine hydrochloride.", "content": "The circular dichroism of diisopropylphosphorylsubtilisins Novo and Carlsberg in both the near- and farultraviolet spectral regions is unaltered by concentrations of guanidine hydrochloride as high as 4 M at neutral pH. At concentrations of guanidine hydrochloride greater than 4 M slow irreversible time-dependent changes, apparently obeying second-order kinetics, are evident in both the near- and far-ultraviolet circular dichroism of these enzymes. Gel filtration studies of inactivated subtilisin enzymes reveal the circular dichroism changes to be accompained by the appearance of aggregated protein material. The changes in circular dichroism and the production of associated subtilisin species are sensitive to protein concentration, denaturant concentrations, and pH. The circular dichroism of active subtilisins Novo and Carlsberg in guanidine hydrochloride exhibits irreversible changes similar to those observed for the inactivated subtilisins. Aggregated protein material is also formed initially in the presence of guanidine hydrochloride, but is rapidly autolyzed to low molecular weight fragments.", "contents": "Circular dichroism and gel filtration behavior of subtilisin enzymes in concentrated solutions of guanidine hydrochloride. The circular dichroism of diisopropylphosphorylsubtilisins Novo and Carlsberg in both the near- and farultraviolet spectral regions is unaltered by concentrations of guanidine hydrochloride as high as 4 M at neutral pH. At concentrations of guanidine hydrochloride greater than 4 M slow irreversible time-dependent changes, apparently obeying second-order kinetics, are evident in both the near- and far-ultraviolet circular dichroism of these enzymes. Gel filtration studies of inactivated subtilisin enzymes reveal the circular dichroism changes to be accompained by the appearance of aggregated protein material. The changes in circular dichroism and the production of associated subtilisin species are sensitive to protein concentration, denaturant concentrations, and pH. The circular dichroism of active subtilisins Novo and Carlsberg in guanidine hydrochloride exhibits irreversible changes similar to those observed for the inactivated subtilisins. Aggregated protein material is also formed initially in the presence of guanidine hydrochloride, but is rapidly autolyzed to low molecular weight fragments."}
{"id": "PMID:238583", "title": "H nuclear magnetic resonance study of restricted internal rotation of N-6,N-6-dimethyladenine in aqueous solution.", "content": "Kinetics of internal rotation about the C(6)-N(6) bond of N-6,N-6-dimethyladenine (M2-6A) was investigated by -1H nuclear magnetic resonance line-shape analysis of the methyl resonances (220 MHz). Rates of rotation were determined for M2-6A deuterated at N(1) and for neutral M2-6A. Activation parameters for monodeuterated M2-6A at 22 degrees are Ea = 13.8kcal/mol, log A = 12.6, incrementG++=14.9 kcal/mol, incrementH++ = 13.1 kcal/mol, incrementS++ = minus 5.8 eu; for neutral M2-6A: Ea = 15.5 kcal/mol, log A = 14.9, incrementG++ = 12.6 kcal/mol, incrementH++ = 14.9 kcal/mol, incrementS++ =7.8 eu. Vertical stacking of bases interferes with internal rotation of the dimethylamino group.", "contents": "H nuclear magnetic resonance study of restricted internal rotation of N-6,N-6-dimethyladenine in aqueous solution. Kinetics of internal rotation about the C(6)-N(6) bond of N-6,N-6-dimethyladenine (M2-6A) was investigated by -1H nuclear magnetic resonance line-shape analysis of the methyl resonances (220 MHz). Rates of rotation were determined for M2-6A deuterated at N(1) and for neutral M2-6A. Activation parameters for monodeuterated M2-6A at 22 degrees are Ea = 13.8kcal/mol, log A = 12.6, incrementG++=14.9 kcal/mol, incrementH++ = 13.1 kcal/mol, incrementS++ = minus 5.8 eu; for neutral M2-6A: Ea = 15.5 kcal/mol, log A = 14.9, incrementG++ = 12.6 kcal/mol, incrementH++ = 14.9 kcal/mol, incrementS++ =7.8 eu. Vertical stacking of bases interferes with internal rotation of the dimethylamino group."}
{"id": "PMID:238584", "title": "Intermolecular complexes between N-methyl-1,4-dihydronicotinamide and flavines. The influence of steric and electronic factors on complex formation and the rate of flavine-dependent dihydronicotinamide dehydrogenation.", "content": "The reaction of N-methyldihydronicotinamide (NMNH) with flavine analogs saturates at high dihydronicotinamide concentrations. Complex formation between the reactants depends mainly on steric but not on electronic factors. Thus flavine analogs that differ up to 243 mV in their oxidation-reduction potential vary only between 0.09 and 0.17 M in Kd. When the flavine plane becomes blocked by bulky substituents, however, complex stability decreases by more than an order of magnitude. NMNH-flavine complexes show long wave optical absorption. The energy of the long wave transition decreases with increasing oxidation-reduction potential of the flavine as expected for charge transfer complexes. The first-order rate constants of flavine-dependent dihydronicotinamide dehydrogenation increase with increasing oxidation-reduction potential of the flavine but they are almost independent of Kd. The reaction is not subject to general acid-base catalysis. Thus flavine-dependent dihydronicotinamide dehydrogenation may be interpreted to proceed via a charge transfer complex between oxidized flavine and reduced nicotinamide. In the rate-limiting conversion of the charge transfer complex into products hydrogen is transferred directly, the rate being governed by the difference in oxidation-reduction potential between flavine and dihydronicotinamide. An alternative mechanism where the observed charge transfer complex is not on the reaction pathway appears to be improbable but cannot be eliminated.", "contents": "Intermolecular complexes between N-methyl-1,4-dihydronicotinamide and flavines. The influence of steric and electronic factors on complex formation and the rate of flavine-dependent dihydronicotinamide dehydrogenation. The reaction of N-methyldihydronicotinamide (NMNH) with flavine analogs saturates at high dihydronicotinamide concentrations. Complex formation between the reactants depends mainly on steric but not on electronic factors. Thus flavine analogs that differ up to 243 mV in their oxidation-reduction potential vary only between 0.09 and 0.17 M in Kd. When the flavine plane becomes blocked by bulky substituents, however, complex stability decreases by more than an order of magnitude. NMNH-flavine complexes show long wave optical absorption. The energy of the long wave transition decreases with increasing oxidation-reduction potential of the flavine as expected for charge transfer complexes. The first-order rate constants of flavine-dependent dihydronicotinamide dehydrogenation increase with increasing oxidation-reduction potential of the flavine but they are almost independent of Kd. The reaction is not subject to general acid-base catalysis. Thus flavine-dependent dihydronicotinamide dehydrogenation may be interpreted to proceed via a charge transfer complex between oxidized flavine and reduced nicotinamide. In the rate-limiting conversion of the charge transfer complex into products hydrogen is transferred directly, the rate being governed by the difference in oxidation-reduction potential between flavine and dihydronicotinamide. An alternative mechanism where the observed charge transfer complex is not on the reaction pathway appears to be improbable but cannot be eliminated."}
{"id": "PMID:238585", "title": "Roles of zinc ion and reduced coenzyme in horse liver alcohol dehydrogenase catalysis. The mechanism of aldehyde activation.", "content": "1,4,5,6-Tetrahydronicotinamide adenine dinucleotide (H2NADH) has been investigated as a reduced coenzyme analog in the reaction between trans-4-N,N-dimethylaminocinnamaldehyde (I) (lambdamax 398 nm, epsilonmax 3.15 X 10-4 M-minus 1 cm-minus 1) and the horse liver alcohol dehydrogenase-NADH complex. These equilibrium binding and temperature-jump kinetic studies establish the following. (i) Substitution of H2NADH for NADH limits reaction to the reversible formation of a new chromophoric species, lambdamax 468 nm, epsilonmax 5.8 x 10-4 M-minus 1 cm-minus 1. This chromophore is demonstrated to be structurally analogous to the transient intermediate formed during the reaction of I with the enzyme-NADH complex [Dunn, M. F., and Hutchison, J. S. (1973), Biochemistry 12, 4882]. (ii) The process of intermediate formation with the enzyme-NADH complex is independent of pH over the range 6.13-10.54. Although studies were limited to the pH range 5.98-8.72, a similar pH independence appears to hold for the H2NADH system. (iii) Within the ternary complex, I is bound within van der Waal's contact distance of the coenzyme nicotinamide ring. (iv) Formation of the transient intermediate does not involve covalent modification of coenzyme. Based on these findings, we conclude that zinc ion has a Lewis acid function in facilitating the chemical activation of the aldehyde carbonyl for reduction, and that reduced coenzyme plays a noncovalent effector role in this substrate activating step.", "contents": "Roles of zinc ion and reduced coenzyme in horse liver alcohol dehydrogenase catalysis. The mechanism of aldehyde activation. 1,4,5,6-Tetrahydronicotinamide adenine dinucleotide (H2NADH) has been investigated as a reduced coenzyme analog in the reaction between trans-4-N,N-dimethylaminocinnamaldehyde (I) (lambdamax 398 nm, epsilonmax 3.15 X 10-4 M-minus 1 cm-minus 1) and the horse liver alcohol dehydrogenase-NADH complex. These equilibrium binding and temperature-jump kinetic studies establish the following. (i) Substitution of H2NADH for NADH limits reaction to the reversible formation of a new chromophoric species, lambdamax 468 nm, epsilonmax 5.8 x 10-4 M-minus 1 cm-minus 1. This chromophore is demonstrated to be structurally analogous to the transient intermediate formed during the reaction of I with the enzyme-NADH complex [Dunn, M. F., and Hutchison, J. S. (1973), Biochemistry 12, 4882]. (ii) The process of intermediate formation with the enzyme-NADH complex is independent of pH over the range 6.13-10.54. Although studies were limited to the pH range 5.98-8.72, a similar pH independence appears to hold for the H2NADH system. (iii) Within the ternary complex, I is bound within van der Waal's contact distance of the coenzyme nicotinamide ring. (iv) Formation of the transient intermediate does not involve covalent modification of coenzyme. Based on these findings, we conclude that zinc ion has a Lewis acid function in facilitating the chemical activation of the aldehyde carbonyl for reduction, and that reduced coenzyme plays a noncovalent effector role in this substrate activating step."}
{"id": "PMID:238586", "title": "Nitrosylhemoglobin Wood: effects of inositol hexaphosphate on thiol reactivity and electron paramagnetic resonance spectrum.", "content": "Properties of Hb Wood (beta-97(FG4)His leads to Leu), a high oxygen affinity hemoglobin with reduced hemeheme interaction, were examined in its nitric oxide liganded form. The reactivity of the beta-93 thiol groups and the electron paramagnetic resonance (EPR) spectrum were examined to determine what effect the amino acid substitution, which occurs at the alpha1beta2 interface, would have on inositol hexaphosphate induced transition of this form of the tetramer. Binding of inositol hexaphosphate (IHP) in a 1:1 stoichiometry was demonstrated. In spite of apparently normal interaction with IHP, there was little or no change in the reactivity of the beta-93 thiol groups and in the electron paramagnetic resonance (EPR) spectrum as contrasted with the marked changes characteristic of normal hemoglobin (HbA). In contrast with NO-HbA, there was also no development of the EPR hyperfine structure in NO-Hb Wood with increased protonation of the protein at pH below 7.0. Taken together with the observations of Henry and Banerjee ((1973), J. Mol. Biol. 73, 469) on the development of NO-Hb EPR hyperfine structure and of Perutz et al. (1974a), Biochemistry 13, 2174) on changes in thiol reactivity with the R leads to T transition, the results suggest that IHP or H+ cannot switch NO-Hb Wood to the T conformation. Since the atomic structures of met- and deoxyhemoglobin offer no indication that His-97 plays any special part in the allosteric mechanism (M. E. Perutz, personal communication), it appears that the replacement of His-97 by Leu reduces the stability of the T structure relative to that of R.", "contents": "Nitrosylhemoglobin Wood: effects of inositol hexaphosphate on thiol reactivity and electron paramagnetic resonance spectrum. Properties of Hb Wood (beta-97(FG4)His leads to Leu), a high oxygen affinity hemoglobin with reduced hemeheme interaction, were examined in its nitric oxide liganded form. The reactivity of the beta-93 thiol groups and the electron paramagnetic resonance (EPR) spectrum were examined to determine what effect the amino acid substitution, which occurs at the alpha1beta2 interface, would have on inositol hexaphosphate induced transition of this form of the tetramer. Binding of inositol hexaphosphate (IHP) in a 1:1 stoichiometry was demonstrated. In spite of apparently normal interaction with IHP, there was little or no change in the reactivity of the beta-93 thiol groups and in the electron paramagnetic resonance (EPR) spectrum as contrasted with the marked changes characteristic of normal hemoglobin (HbA). In contrast with NO-HbA, there was also no development of the EPR hyperfine structure in NO-Hb Wood with increased protonation of the protein at pH below 7.0. Taken together with the observations of Henry and Banerjee ((1973), J. Mol. Biol. 73, 469) on the development of NO-Hb EPR hyperfine structure and of Perutz et al. (1974a), Biochemistry 13, 2174) on changes in thiol reactivity with the R leads to T transition, the results suggest that IHP or H+ cannot switch NO-Hb Wood to the T conformation. Since the atomic structures of met- and deoxyhemoglobin offer no indication that His-97 plays any special part in the allosteric mechanism (M. E. Perutz, personal communication), it appears that the replacement of His-97 by Leu reduces the stability of the T structure relative to that of R."}
{"id": "PMID:238587", "title": "Assignment of the histidine proton magnetic resonance peaks of soybean trypsin inhibitor (Kunitz) by a differertial deuterium exchange technique.", "content": "Deuterium exchange at the C(2)-H position of the two histidine residues of native soybean trypsin inhibitor (Kunitz) in 2-H2O was followed by 1-H nuclear magnetic resonance (NMR) spectroscopy. The two histidine residues of soybean trypsin inhibitor exchange at significantly different rates at pH* 5.00, 40 degrees. Half-times observed were: peak H1, t1/2=61 plus or minus 2 days; peak H2, T1/2=24 plus or minus 2 days. Differentially deuterated soybean trypsin inhibitor was cleaved by cyanogen bromide into two fragments each containing one histidine residue. The deuterium content of the histidine residue of each separated fragment was analyzed by 1H NMR spectroscopy. Hisidine-71 in fragment 1-114 showed approximately twice the deuterium content of His-157 in fragment 115-181. These results lead to the assignment of 1H NMR peak H1 to His-157 and peak H2 to His-71. These assignments were extended to the histidine peaks of trypsin-modified soybean trypsin inhibitor by converting the differentially deuterated virgin soybean trypsin inhibitor to the modified form. The correlation of histidine peaks in virgin amd modified soybean trypsin inhibitors was the same as proposed earlier on the basis of pK arguments. The results demonstrate that His-71 is the residue whose pK value is raised from 5.27 to 5.91 on trypsin modification of soybean trypsin inhibitor [Markley, J. L., (1973), Biochemistry 12, 2245].", "contents": "Assignment of the histidine proton magnetic resonance peaks of soybean trypsin inhibitor (Kunitz) by a differertial deuterium exchange technique. Deuterium exchange at the C(2)-H position of the two histidine residues of native soybean trypsin inhibitor (Kunitz) in 2-H2O was followed by 1-H nuclear magnetic resonance (NMR) spectroscopy. The two histidine residues of soybean trypsin inhibitor exchange at significantly different rates at pH* 5.00, 40 degrees. Half-times observed were: peak H1, t1/2=61 plus or minus 2 days; peak H2, T1/2=24 plus or minus 2 days. Differentially deuterated soybean trypsin inhibitor was cleaved by cyanogen bromide into two fragments each containing one histidine residue. The deuterium content of the histidine residue of each separated fragment was analyzed by 1H NMR spectroscopy. Hisidine-71 in fragment 1-114 showed approximately twice the deuterium content of His-157 in fragment 115-181. These results lead to the assignment of 1H NMR peak H1 to His-157 and peak H2 to His-71. These assignments were extended to the histidine peaks of trypsin-modified soybean trypsin inhibitor by converting the differentially deuterated virgin soybean trypsin inhibitor to the modified form. The correlation of histidine peaks in virgin amd modified soybean trypsin inhibitors was the same as proposed earlier on the basis of pK arguments. The results demonstrate that His-71 is the residue whose pK value is raised from 5.27 to 5.91 on trypsin modification of soybean trypsin inhibitor [Markley, J. L., (1973), Biochemistry 12, 2245]."}
{"id": "PMID:238588", "title": "An electrophoretic study of reversible protein denaturation: chymotrypsinogen at high pressures.", "content": "When reversible denaturation of chymotrypsinogen is produced at elevated hydrostatic pressures, conformational relaxation can occur quite slowly, allowing electrophoretic separation of the principal states from the equilibrium mixture. In this work we report experimental concentration distribution patterns obtained at pH 2.03 at a temperature of 20.5 degrees and find them to be reasonably consistent with the behavior that is expected from a simple two-state isomerism. However, the results do not at all rule out the existence of low levels of intermediate states.", "contents": "An electrophoretic study of reversible protein denaturation: chymotrypsinogen at high pressures. When reversible denaturation of chymotrypsinogen is produced at elevated hydrostatic pressures, conformational relaxation can occur quite slowly, allowing electrophoretic separation of the principal states from the equilibrium mixture. In this work we report experimental concentration distribution patterns obtained at pH 2.03 at a temperature of 20.5 degrees and find them to be reasonably consistent with the behavior that is expected from a simple two-state isomerism. However, the results do not at all rule out the existence of low levels of intermediate states."}
{"id": "PMID:238589", "title": "Hydrogen-tritium exchange kinetics of soybean trypsin inhibitor (Kunitz). Solvent accessibility in the folded conformation.", "content": "The hydrogen exchange kinetics of Kunitz soybean trypsin inhibitor (STI) has been studied at pH 2, 3, and 6.5. From the temperature dependence of proton exchange at low pH, THE CONTRIBUTION OF MAJOR, REVERSIBLE PROTEIN UNFOLDING To the hydrogen exchange kinetics has been determined. Exchange directly from the folded conformation is characterized by an apparent activation energy (E*app) of approximately 25 kcal/mol, close to that of the chemical exchange step. At pH 6.5 the protein is more temperature stable than at low pH, and exchange of all but congruent to 8 protons can be observed to exchange with E*app congruent to 27 kcal/mol. This implies that all but congruent to 8 protons are accessible to exchange with solvent in the solution structure of folded STI. Estimates can be made of the average number of water molecules per molecule of STI consistent with a solvent accessibility model of hydrogen exchange kinetics. These estimates indicate that very few water molecules within the protein matrix are necessary to explain the exchange data. Calculations are done for the STI hydrogen exchange kinetics at pH 3, 30 degrees, approximating STI structure by a sphere of radius = 18 A. These calculations indicate an average of congruent to 4 water molecules in the shell from 13 to 16 A. from the center of the molecule, while less than 1 water molecule is indicated in the innermost 13 A. These calculations also suggest that there are congruent to 190 water molecules associated with the outermost 1.5-2 A of the sphere. While these values are consistent with a hydrophobic region in the central protein matrix, they indicate more solvent accessibility in the outer 1/3 of the molecule than the static accessibility estimates made from X-ray coordinates. Our results suggest that any protein movements or fluctuations responsible for solvent accessibility in proton exchange processes are localized in the outer regions of the globular structure.", "contents": "Hydrogen-tritium exchange kinetics of soybean trypsin inhibitor (Kunitz). Solvent accessibility in the folded conformation. The hydrogen exchange kinetics of Kunitz soybean trypsin inhibitor (STI) has been studied at pH 2, 3, and 6.5. From the temperature dependence of proton exchange at low pH, THE CONTRIBUTION OF MAJOR, REVERSIBLE PROTEIN UNFOLDING To the hydrogen exchange kinetics has been determined. Exchange directly from the folded conformation is characterized by an apparent activation energy (E*app) of approximately 25 kcal/mol, close to that of the chemical exchange step. At pH 6.5 the protein is more temperature stable than at low pH, and exchange of all but congruent to 8 protons can be observed to exchange with E*app congruent to 27 kcal/mol. This implies that all but congruent to 8 protons are accessible to exchange with solvent in the solution structure of folded STI. Estimates can be made of the average number of water molecules per molecule of STI consistent with a solvent accessibility model of hydrogen exchange kinetics. These estimates indicate that very few water molecules within the protein matrix are necessary to explain the exchange data. Calculations are done for the STI hydrogen exchange kinetics at pH 3, 30 degrees, approximating STI structure by a sphere of radius = 18 A. These calculations indicate an average of congruent to 4 water molecules in the shell from 13 to 16 A. from the center of the molecule, while less than 1 water molecule is indicated in the innermost 13 A. These calculations also suggest that there are congruent to 190 water molecules associated with the outermost 1.5-2 A of the sphere. While these values are consistent with a hydrophobic region in the central protein matrix, they indicate more solvent accessibility in the outer 1/3 of the molecule than the static accessibility estimates made from X-ray coordinates. Our results suggest that any protein movements or fluctuations responsible for solvent accessibility in proton exchange processes are localized in the outer regions of the globular structure."}
{"id": "PMID:238590", "title": "Hydrogen exchange kinetics changes upon formation of the soybean trypsin inhibitor-trypsin complex.", "content": "The hydrogen exchange kinetics of the complex of trypsin-soybean trypsin inhibitor (Kunitz) have been compared to the calculated sum of the exchange kinetics for the inhibitor and trypsin measured separately. The exchange rates observed for the complex are substantially less than the sum of the exchange rates in the two individual proteins. These results cannot be accounted for by changes in intermolecular or intramolecular hydrogen bonding. The decrease in exchange rates in the complex are ascribed to changes in solvent accessibility in the component proteins.", "contents": "Hydrogen exchange kinetics changes upon formation of the soybean trypsin inhibitor-trypsin complex. The hydrogen exchange kinetics of the complex of trypsin-soybean trypsin inhibitor (Kunitz) have been compared to the calculated sum of the exchange kinetics for the inhibitor and trypsin measured separately. The exchange rates observed for the complex are substantially less than the sum of the exchange rates in the two individual proteins. These results cannot be accounted for by changes in intermolecular or intramolecular hydrogen bonding. The decrease in exchange rates in the complex are ascribed to changes in solvent accessibility in the component proteins."}
{"id": "PMID:238591", "title": "High-resolution proton nuclear magnetic resonance studies of sickle cell hemoglobin.", "content": "High-resoluiton proton nuclear magnetic resonance spectroscopy at 250 MHz has been used to investigate sickle cell hemoglobin. The hyperfine shifted, the ring-current shifted, and the exchangeable proton resonances suggest that the heme environment and the subunit interfaces of the sickle cell hemoglobin molecule are normal. These results suggest that the low oxygen affinity in sickle cell blood is not due to conformational alterations in the heme environment or the subunit interfaces. The C-2 proton resonances of certain histidyl residues can serve as structural probes for the surface conformation of the hemoglobin molecule. Several sharp resonances in sickle cell hemoglobin are shifted upfield from their positions in normal adult hemoglobin. These upfield shifts, which are observed in both oxy and deoxy forms of the molecule under various experimental conditions, suggest that some of the surface residues of sickle cell hemoglobin are altered and they may be in a more hydrophobic environment as compared with that of normal human adult hemoglobin. These differences in surface conformation are pH and ionic strength specific. In particular, upon the addition of organic phosphates to normal and sickle cell hemoglobin samples, the differences in their aromatic proton resonances diminish. These changes in the surface conformation may, in part, be responsible for the abnormal properties of sickle cell hemoglobin.", "contents": "High-resolution proton nuclear magnetic resonance studies of sickle cell hemoglobin. High-resoluiton proton nuclear magnetic resonance spectroscopy at 250 MHz has been used to investigate sickle cell hemoglobin. The hyperfine shifted, the ring-current shifted, and the exchangeable proton resonances suggest that the heme environment and the subunit interfaces of the sickle cell hemoglobin molecule are normal. These results suggest that the low oxygen affinity in sickle cell blood is not due to conformational alterations in the heme environment or the subunit interfaces. The C-2 proton resonances of certain histidyl residues can serve as structural probes for the surface conformation of the hemoglobin molecule. Several sharp resonances in sickle cell hemoglobin are shifted upfield from their positions in normal adult hemoglobin. These upfield shifts, which are observed in both oxy and deoxy forms of the molecule under various experimental conditions, suggest that some of the surface residues of sickle cell hemoglobin are altered and they may be in a more hydrophobic environment as compared with that of normal human adult hemoglobin. These differences in surface conformation are pH and ionic strength specific. In particular, upon the addition of organic phosphates to normal and sickle cell hemoglobin samples, the differences in their aromatic proton resonances diminish. These changes in the surface conformation may, in part, be responsible for the abnormal properties of sickle cell hemoglobin."}
{"id": "PMID:238593", "title": "A kinetic study of the reaction between cytochrome c peroxidase and hydrogen peroxide. Dependence on pH and ionic strength.", "content": "The rate of the reaction between cytochrome c peroxidase and hydrogen peroxide was investigated using the stopped-flow technique. The apparent bimolecular rate constant was determined between pH 3.3 and pH 11 as a function of ionic strength. The pH dependence of the apparent bimolecular rate constant can be explained by assuming that two ionizable groups on the enzyme strongly influence the rate of the reaction. At 0.1 M ionic strength, a group with a pKa of 5.5 must be unprotonated and a group with a pKa of 9.8 must be protonated for the enzyme to react rapidly with hydrogen peroxide. The apparent acid dissociation constants depend upon the ionic strength. The true bimolecular rate constant has a value of (4.5 +/- 0.3) X 10(7) M-1 sec-1 and is independent of ionic strength.", "contents": "A kinetic study of the reaction between cytochrome c peroxidase and hydrogen peroxide. Dependence on pH and ionic strength. The rate of the reaction between cytochrome c peroxidase and hydrogen peroxide was investigated using the stopped-flow technique. The apparent bimolecular rate constant was determined between pH 3.3 and pH 11 as a function of ionic strength. The pH dependence of the apparent bimolecular rate constant can be explained by assuming that two ionizable groups on the enzyme strongly influence the rate of the reaction. At 0.1 M ionic strength, a group with a pKa of 5.5 must be unprotonated and a group with a pKa of 9.8 must be protonated for the enzyme to react rapidly with hydrogen peroxide. The apparent acid dissociation constants depend upon the ionic strength. The true bimolecular rate constant has a value of (4.5 +/- 0.3) X 10(7) M-1 sec-1 and is independent of ionic strength."}
{"id": "PMID:238592", "title": "Characterization and properties of Pholas luciferase as a metalloglycoprotein.", "content": "The luciferase of the bioluminescent boring mollusc, Pholas dactylus, has been purified by a new method which includes centrifugation in cesium chloride gradients. Homogeneous preparations have been obtained and molecular weight determinations and subunit analysis support the idea that this preparation is an oxyluciferin-luciferase complex. The preparation catalyzes oxidation of ascorbic acid in presence of H2O2, and this peroxidase activitity has been used for characterization (thermal and pH stabilities, activity as a function of pH, isoelectric point, turnover number). The existence of two atoms of copper has been established and their involvement in the peroxidase activity indicated. Chemical analyses have shown that Pholad luciferase is a glycoprotein and the existence of glucosamine, fucose, mannose, and galactose residues has been demonstrated. The apparent buoyant dentisty (1.340), the sedimentation coefficient (10.7 S), the Stoke's radius (83 A), the partial specific volum (0.707), and the molecular weight (350,000) have been determined. The frictional ratio (flf0 = 1.8) derived from the Stoke's radius indicates that the molecule is asymmetric. The quaternary structure has been examined. Subunits of molecular weight 150,000 and 46,000 have been observed. The latter has electrophoretic properties identical with luciferin or oxyluciferin.", "contents": "Characterization and properties of Pholas luciferase as a metalloglycoprotein. The luciferase of the bioluminescent boring mollusc, Pholas dactylus, has been purified by a new method which includes centrifugation in cesium chloride gradients. Homogeneous preparations have been obtained and molecular weight determinations and subunit analysis support the idea that this preparation is an oxyluciferin-luciferase complex. The preparation catalyzes oxidation of ascorbic acid in presence of H2O2, and this peroxidase activitity has been used for characterization (thermal and pH stabilities, activity as a function of pH, isoelectric point, turnover number). The existence of two atoms of copper has been established and their involvement in the peroxidase activity indicated. Chemical analyses have shown that Pholad luciferase is a glycoprotein and the existence of glucosamine, fucose, mannose, and galactose residues has been demonstrated. The apparent buoyant dentisty (1.340), the sedimentation coefficient (10.7 S), the Stoke's radius (83 A), the partial specific volum (0.707), and the molecular weight (350,000) have been determined. The frictional ratio (flf0 = 1.8) derived from the Stoke's radius indicates that the molecule is asymmetric. The quaternary structure has been examined. Subunits of molecular weight 150,000 and 46,000 have been observed. The latter has electrophoretic properties identical with luciferin or oxyluciferin."}
{"id": "PMID:238594", "title": "A nuclear magnetic resonance study of nicotinamide adenine dinucleotide phosphate binding to Lactobacillus casei dihydrofolate reductase.", "content": "The binding of NADP+ to dihydrofolate reductase (EC 1.5.1.3) in the presence and absence of substrate analogs has been studied using 1H and 13C nuclear magnetic resonance (NMR). NADP+ binds strongly to the enzyme alone and in the presence of folate, aminopterin, and methotrexate with a stoichiometry of 1 mol of NADP+/mol of enzyme. In the 13C spectra of the binary and ternary complexes, separate signals were observed for the carboxamide carbon of free and bound [13CO]NADP+ (enriched 90% in 13C). The 13C signal of the NADP+-reductase complex is much broader than that in the ternary complex with methotrexate because of exchange line broadening on the binary complex signal. From the difference in line widths (17.5 +/- 3.0 Hz) an estimate of the dissociation rate constant of the binary complex has been obtained (55 +/- 10 sec-1). The dissociation rate of the NADP+-reductase complex is not the rate-limiting step in the overall reaction. In the various complexes studied large 13C chemical shifts were measured for bound [13CO]NADP+ relative to free NADP+ (upfield shifts of 1.6-4.3 ppm). The most likely origin of the bound shifts lies in the effects on the shieldings of electric fields from nearby charged groups. For the NADP+-reductase-folate system two 13C signals from bound NADP+ are observed indicating the presence of more than one form of the ternary complex. The IH spectra of the binary and ternary complexes confirm both the stoichiometry and the value of the dissociation rate constant obtained from the 13C experiments. Substantial changes in the IH spectrum of the protein were observed in the different complexes and these are distinct from those seen in the presence of NADPH.", "contents": "A nuclear magnetic resonance study of nicotinamide adenine dinucleotide phosphate binding to Lactobacillus casei dihydrofolate reductase. The binding of NADP+ to dihydrofolate reductase (EC 1.5.1.3) in the presence and absence of substrate analogs has been studied using 1H and 13C nuclear magnetic resonance (NMR). NADP+ binds strongly to the enzyme alone and in the presence of folate, aminopterin, and methotrexate with a stoichiometry of 1 mol of NADP+/mol of enzyme. In the 13C spectra of the binary and ternary complexes, separate signals were observed for the carboxamide carbon of free and bound [13CO]NADP+ (enriched 90% in 13C). The 13C signal of the NADP+-reductase complex is much broader than that in the ternary complex with methotrexate because of exchange line broadening on the binary complex signal. From the difference in line widths (17.5 +/- 3.0 Hz) an estimate of the dissociation rate constant of the binary complex has been obtained (55 +/- 10 sec-1). The dissociation rate of the NADP+-reductase complex is not the rate-limiting step in the overall reaction. In the various complexes studied large 13C chemical shifts were measured for bound [13CO]NADP+ relative to free NADP+ (upfield shifts of 1.6-4.3 ppm). The most likely origin of the bound shifts lies in the effects on the shieldings of electric fields from nearby charged groups. For the NADP+-reductase-folate system two 13C signals from bound NADP+ are observed indicating the presence of more than one form of the ternary complex. The IH spectra of the binary and ternary complexes confirm both the stoichiometry and the value of the dissociation rate constant obtained from the 13C experiments. Substantial changes in the IH spectrum of the protein were observed in the different complexes and these are distinct from those seen in the presence of NADPH."}
{"id": "PMID:238595", "title": "Preparation and properties of three specific active derivatives of ribonuclease A obtained by methylation of methionine residues in 8 M urea.", "content": "In 8 M urea at low pH, CH3I reacts specifically with the four methionine residues of ribonuclease A, and all four residues react at the same rate. Uon removal of the denaturant, only unmodified ribonuclease and 3 of the 15 possible derivatives modified on methionine refold to regenerate activity. All the enzymatic activity is recored after chromatography on IRC-50 and the four active proteins separate from each other and from the 12 inactive derivatives, which are not eluted from the resin under the conditions used. By the use of 14CH3I, performic acid oxidation, chymotryptic digestion, and separation of the resulting peptides by ion exchange, the active species were determined to be unmodified ribonuclease, CH3Met-29-RNase, CH3Met-79-RNase, and CH3Met-29, CH3Met-79-RNase. these proteins have melting temperatures of 63, 58, 43, and 36 degrees, respectively, at pH 6.3-70. Methylation at methionine-29 or -79 has no effect on enzymatic activity. Conversely, methylation at methionine-13 or -30 prevents refolding to an active conformation at 25 degrees elution from IRC-50. These results are consistent with the positions of the four methionine residues in crystals of ribonuclease A and ribonuclease S as determined by X-ray diffraction.", "contents": "Preparation and properties of three specific active derivatives of ribonuclease A obtained by methylation of methionine residues in 8 M urea. In 8 M urea at low pH, CH3I reacts specifically with the four methionine residues of ribonuclease A, and all four residues react at the same rate. Uon removal of the denaturant, only unmodified ribonuclease and 3 of the 15 possible derivatives modified on methionine refold to regenerate activity. All the enzymatic activity is recored after chromatography on IRC-50 and the four active proteins separate from each other and from the 12 inactive derivatives, which are not eluted from the resin under the conditions used. By the use of 14CH3I, performic acid oxidation, chymotryptic digestion, and separation of the resulting peptides by ion exchange, the active species were determined to be unmodified ribonuclease, CH3Met-29-RNase, CH3Met-79-RNase, and CH3Met-29, CH3Met-79-RNase. these proteins have melting temperatures of 63, 58, 43, and 36 degrees, respectively, at pH 6.3-70. Methylation at methionine-29 or -79 has no effect on enzymatic activity. Conversely, methylation at methionine-13 or -30 prevents refolding to an active conformation at 25 degrees elution from IRC-50. These results are consistent with the positions of the four methionine residues in crystals of ribonuclease A and ribonuclease S as determined by X-ray diffraction."}
{"id": "PMID:238596", "title": "Gamma-glutamyltransferase from azo dye induced hepatoma and fetal rat liver.  Similarities in their kinetic and immunological properties.", "content": "Some properties of gamma-glutamyltransferase ((gamma-glutamyl)-peptide: amino-acid gamma-glutamyltransferase EC 2.3.2.2) from azo dye induced hepatoma and fetal rat liver were studied using kinetic and immunological criteria. There was no significant difference between the hepatoma enzyme and fetal rat liver enzyme in some of their catalytic properties. Antisera against the purified hepatoma enzyme also reacted to the fetal rat liver enzyme in the inhibition test and the precipitin reaction. A structural similarity between the hepatoma enzyme and fetal rat liver enzyme was observed and the acquirement of fetal characteristics in hepatoma was discussed.", "contents": "Gamma-glutamyltransferase from azo dye induced hepatoma and fetal rat liver.  Similarities in their kinetic and immunological properties. Some properties of gamma-glutamyltransferase ((gamma-glutamyl)-peptide: amino-acid gamma-glutamyltransferase EC 2.3.2.2) from azo dye induced hepatoma and fetal rat liver were studied using kinetic and immunological criteria. There was no significant difference between the hepatoma enzyme and fetal rat liver enzyme in some of their catalytic properties. Antisera against the purified hepatoma enzyme also reacted to the fetal rat liver enzyme in the inhibition test and the precipitin reaction. A structural similarity between the hepatoma enzyme and fetal rat liver enzyme was observed and the acquirement of fetal characteristics in hepatoma was discussed."}
{"id": "PMID:238597", "title": "Surface-bound aspartate aminotransferase on collagen films.  Compared properties with native enzyme.", "content": "Aspartate aminotransferase (L-aspartate : 2-oxoglutarate aminotransferase, EC 2.6.1.1) has been covalently bound to chemically activated collagen films. This enzyme had never previously been coupled to any other solid support. The coupling method, including acyl azide formation on the carrier, allowed coupling of many other enzymes. A systematic study of coupling conditions has been performed; influence of time of coupling and of concentration of coupling solution on the enzymatic activity retained on the film. Coupling solutions could be used for several successive couplings. To determine the yield of binding, N-[14C] ethylmaleimide-labelled enzyme was prepared fully active and bound to collagen films. After lyophilisation the film retained most of its activity when stored in buffer and the half-life of the enzymatic film was about ten months. pH Dependence and activation energy were about the same for soluble and coupled enzyme. Coupling protects against thermal denaturation and increases the stability of the enzyme; the enzymatic film could be used repeatedly. Kinetics were somewhat modified in the coupled enzyme as compared to the enzyme in solution. Glutamate appeared more available while oxaloacetate seemed to be limiting. These modifications might be due to the proteic support itself. The enzymatic films also revealed themselves as a good tool for industrial or clinical purposes as well as for studying the mechanism of enzyme action.", "contents": "Surface-bound aspartate aminotransferase on collagen films.  Compared properties with native enzyme. Aspartate aminotransferase (L-aspartate : 2-oxoglutarate aminotransferase, EC 2.6.1.1) has been covalently bound to chemically activated collagen films. This enzyme had never previously been coupled to any other solid support. The coupling method, including acyl azide formation on the carrier, allowed coupling of many other enzymes. A systematic study of coupling conditions has been performed; influence of time of coupling and of concentration of coupling solution on the enzymatic activity retained on the film. Coupling solutions could be used for several successive couplings. To determine the yield of binding, N-[14C] ethylmaleimide-labelled enzyme was prepared fully active and bound to collagen films. After lyophilisation the film retained most of its activity when stored in buffer and the half-life of the enzymatic film was about ten months. pH Dependence and activation energy were about the same for soluble and coupled enzyme. Coupling protects against thermal denaturation and increases the stability of the enzyme; the enzymatic film could be used repeatedly. Kinetics were somewhat modified in the coupled enzyme as compared to the enzyme in solution. Glutamate appeared more available while oxaloacetate seemed to be limiting. These modifications might be due to the proteic support itself. The enzymatic films also revealed themselves as a good tool for industrial or clinical purposes as well as for studying the mechanism of enzyme action."}
{"id": "PMID:238598", "title": "The reaction of tris (hydroxymethyl) aminomethane with calf intestinal alkaline phosphatase.", "content": "The effect of tris (hydroxymethyl) aminomethane concentrations on the rate of calf intestinal alkaline phosphatase-catalyzed hydrolysis of p-nitrophenyl phosphate was studied, in the pH range 8-10, where no transphosphorylation reaction could be detected. Kinetic analysis of the results permitted description of the effect of Tris concentrations T on the rate of enzyme catalyzed hydrolysis (V) by the following equation: (see article). The rate-accelerating effect of Tris concentrations can be ascribed to two different mechanisms: At moderate Tris concentrations (0.01-0.20 M) the enzyme forms a reversible addition complex with a Tris molecule. This complex has an enhanced catalytic activity. We suggest that the binding of Tris to the enzyme could potentiate a second active site of the enzyme, due to its ionization effect upon an acidic group of the enzyme of pK = 8.9. The modest linear rate accelerating effect of Tris at high concentrations (0.20-0.60 M) could be ascribed to the change of the dielectric constant of the medium, the degree of solvation of the protein, or change in the tertiary structure of the enzyme.", "contents": "The reaction of tris (hydroxymethyl) aminomethane with calf intestinal alkaline phosphatase. The effect of tris (hydroxymethyl) aminomethane concentrations on the rate of calf intestinal alkaline phosphatase-catalyzed hydrolysis of p-nitrophenyl phosphate was studied, in the pH range 8-10, where no transphosphorylation reaction could be detected. Kinetic analysis of the results permitted description of the effect of Tris concentrations T on the rate of enzyme catalyzed hydrolysis (V) by the following equation: (see article). The rate-accelerating effect of Tris concentrations can be ascribed to two different mechanisms: At moderate Tris concentrations (0.01-0.20 M) the enzyme forms a reversible addition complex with a Tris molecule. This complex has an enhanced catalytic activity. We suggest that the binding of Tris to the enzyme could potentiate a second active site of the enzyme, due to its ionization effect upon an acidic group of the enzyme of pK = 8.9. The modest linear rate accelerating effect of Tris at high concentrations (0.20-0.60 M) could be ascribed to the change of the dielectric constant of the medium, the degree of solvation of the protein, or change in the tertiary structure of the enzyme."}
{"id": "PMID:238599", "title": "Resolution, purification and characterization of the orthophosphate releasing activities from fracture callus calcifying cartilage.", "content": "Callus calcifying cartilage alkaline phosphatase was resolved by DEAE-cellulose column chromatography into two distinct phsophatase activities. The phosphatase activity which was eluted first from the column, (phosphatase I), was active towards a variety of phosphate esters, sodium pyrophosphatase and several linear polyphosphates, while the second phosphatase activity , (phosphatase II), was active toward simple phosphate esters but not towards sodium pyrophosphate and linear oligo or polyphosphates. All the phosphate esters, sodium pyrophosphate and polyphosphates at higher concentrations were inhibitory for phosphatase I. The modulating effects of magnesium, calcium, zinc and other phosphatase modulators have been investigated. Both phosphatases from callus calcifying cartilage were found to be substrates of neuraminidase with sialic acid as the product. Besides the difference in their specificity, the phosphatases were found to be immunologically different and to have different molecular weights, strong indication that they are different enzymes.", "contents": "Resolution, purification and characterization of the orthophosphate releasing activities from fracture callus calcifying cartilage. Callus calcifying cartilage alkaline phosphatase was resolved by DEAE-cellulose column chromatography into two distinct phsophatase activities. The phosphatase activity which was eluted first from the column, (phosphatase I), was active towards a variety of phosphate esters, sodium pyrophosphatase and several linear polyphosphates, while the second phosphatase activity , (phosphatase II), was active toward simple phosphate esters but not towards sodium pyrophosphate and linear oligo or polyphosphates. All the phosphate esters, sodium pyrophosphate and polyphosphates at higher concentrations were inhibitory for phosphatase I. The modulating effects of magnesium, calcium, zinc and other phosphatase modulators have been investigated. Both phosphatases from callus calcifying cartilage were found to be substrates of neuraminidase with sialic acid as the product. Besides the difference in their specificity, the phosphatases were found to be immunologically different and to have different molecular weights, strong indication that they are different enzymes."}
{"id": "PMID:238600", "title": "The relationship between different forms of human alpha-mannosidase.", "content": "The tissue distribution and some properties of human alpha-mannosidase (alpha-D-mannoside mannohydrolase EC 3.2.1.24) have been studied. The acidic forms of the enzyme were fairly stable, whereas the neutral forms easily lost enzymic activity. The acidic forms were sensitive to neuraminidase but the neutral forms were unaffected. The experiments indicate that the acidic components are closely related to each other, differing only in sialic acid content and possibly conformation. The neutral forms of the enzyme are probably quite different from the acidic forms both in structure and cellular function.", "contents": "The relationship between different forms of human alpha-mannosidase. The tissue distribution and some properties of human alpha-mannosidase (alpha-D-mannoside mannohydrolase EC 3.2.1.24) have been studied. The acidic forms of the enzyme were fairly stable, whereas the neutral forms easily lost enzymic activity. The acidic forms were sensitive to neuraminidase but the neutral forms were unaffected. The experiments indicate that the acidic components are closely related to each other, differing only in sialic acid content and possibly conformation. The neutral forms of the enzyme are probably quite different from the acidic forms both in structure and cellular function."}
{"id": "PMID:238601", "title": "Purification and characterization of Aspergillus niger exo-1,4-glucosidase.", "content": "A specific exo-1,4-glucosidase (1,4-alpha-D-glucan glucohydrooase, EC 3.2.1.3) from Aspergillus niger has been partially purified and subsequently characterized by biochemical, physico-chemical and optical methods. Molecular sieve chromatography yields an enzyme with maximal activity at pH 4.2-4.5 close to its isoelectric point. Reduction and carboxymethylation leads to complete loss of activity and O-acetylation of 3 of the 13 tyrosine residues results in loss of 20 % of the activity. Sodium dodecylsulfate-polyacrylamide gel electrophoresis indicates that the native enzyme consists of two major components of molecular weights 63 000 and 57 500, respectively. Small amounts of dissociated material of molecular weight 28 000 and 16 000 as well as aggregates of the order of 100 000 are also present to the extent of 2-5% of the total potein. Following reduction and carboxymethylation under forcing conditions, the bands around 60 000 diminish and the 28 000-30 000, 16 000 and aggregate bands are dominant...", "contents": "Purification and characterization of Aspergillus niger exo-1,4-glucosidase. A specific exo-1,4-glucosidase (1,4-alpha-D-glucan glucohydrooase, EC 3.2.1.3) from Aspergillus niger has been partially purified and subsequently characterized by biochemical, physico-chemical and optical methods. Molecular sieve chromatography yields an enzyme with maximal activity at pH 4.2-4.5 close to its isoelectric point. Reduction and carboxymethylation leads to complete loss of activity and O-acetylation of 3 of the 13 tyrosine residues results in loss of 20 % of the activity. Sodium dodecylsulfate-polyacrylamide gel electrophoresis indicates that the native enzyme consists of two major components of molecular weights 63 000 and 57 500, respectively. Small amounts of dissociated material of molecular weight 28 000 and 16 000 as well as aggregates of the order of 100 000 are also present to the extent of 2-5% of the total potein. Following reduction and carboxymethylation under forcing conditions, the bands around 60 000 diminish and the 28 000-30 000, 16 000 and aggregate bands are dominant..."}
{"id": "PMID:238603", "title": "Formation of a covalent intermediate between alpha-chymotryspin and the B-chain of insulin during enzyme-catalyzed hydrolysis.", "content": "The reaction between alpha-chymotrypsin (EC 3.3.21.1) and the B-chain of bovine insulin was studied radiochemically, by using the 3 5S-labelled sulfo B-chain. After incubation at pH 8.0, interrupted by the addition of trichloroacetic acid, a radioactive product was isolated from the reaction mixture. The labelled product was eluted in parallel with the enzyme in gel chromatography, and its properties at different H+ concentrations indicated that chemically it was an ester, i.e. a covalent enzyme-substrate intermediate. No interaction between sulfo beta-chain and alpha-chymotrypsinogen or phenyl-methyl sulfonyl fluoride-inhibited alpha-chymotrypsin was obtained during identical conditions.", "contents": "Formation of a covalent intermediate between alpha-chymotryspin and the B-chain of insulin during enzyme-catalyzed hydrolysis. The reaction between alpha-chymotrypsin (EC 3.3.21.1) and the B-chain of bovine insulin was studied radiochemically, by using the 3 5S-labelled sulfo B-chain. After incubation at pH 8.0, interrupted by the addition of trichloroacetic acid, a radioactive product was isolated from the reaction mixture. The labelled product was eluted in parallel with the enzyme in gel chromatography, and its properties at different H+ concentrations indicated that chemically it was an ester, i.e. a covalent enzyme-substrate intermediate. No interaction between sulfo beta-chain and alpha-chymotrypsinogen or phenyl-methyl sulfonyl fluoride-inhibited alpha-chymotrypsin was obtained during identical conditions."}
{"id": "PMID:238604", "title": "Studies on the interaction between Streptomyces pepsin inhibitor and several acid proteinases by means of a zinc(II)-dye complex as a probe.", "content": "The zinc(II) complex of pyridine-2-azo-p-dimethylaniline is bound to several acid proteinases, at pH 5.0, accompanied by a change is the visible absorption spectrum. Streptomyces pepsin inhibitor, which was discovered by Satoi and Murao (Satoi, S. and Murao, S. (1970) Agric. Biol. Chem. 34, 1265-1267 and Satoi, S. and Murao, S. (1971) Agric. Biol. Chem. 35, 1482-1487), is also bound to acid proteinases. Spectrophotometric studies with ten acid proteinases from different sources have revealed that in several acid proteinases, zinc(II)-pyridine-2-azo-p-dimethylaniline is released from the enzyme by the inhibitor, while some acid proteinase forms a quaternary complex, zinc(II)-pyridine-2-azo-p-dimethylaniline-inhibitor-enzyme. It is speculated that zinc(II)-pyridine-2-azo-p-dimethylaniline is bound to two catalytic carboxylate groups in the active site of the acid proteinases and the inhibitor is bound mainly to the substrate-binding site of the enzymes. The binding of the inhibitor may overlap the catalytic site completely or partially. The degree of overlapping is characteristic of the kind of acid proteinases.", "contents": "Studies on the interaction between Streptomyces pepsin inhibitor and several acid proteinases by means of a zinc(II)-dye complex as a probe. The zinc(II) complex of pyridine-2-azo-p-dimethylaniline is bound to several acid proteinases, at pH 5.0, accompanied by a change is the visible absorption spectrum. Streptomyces pepsin inhibitor, which was discovered by Satoi and Murao (Satoi, S. and Murao, S. (1970) Agric. Biol. Chem. 34, 1265-1267 and Satoi, S. and Murao, S. (1971) Agric. Biol. Chem. 35, 1482-1487), is also bound to acid proteinases. Spectrophotometric studies with ten acid proteinases from different sources have revealed that in several acid proteinases, zinc(II)-pyridine-2-azo-p-dimethylaniline is released from the enzyme by the inhibitor, while some acid proteinase forms a quaternary complex, zinc(II)-pyridine-2-azo-p-dimethylaniline-inhibitor-enzyme. It is speculated that zinc(II)-pyridine-2-azo-p-dimethylaniline is bound to two catalytic carboxylate groups in the active site of the acid proteinases and the inhibitor is bound mainly to the substrate-binding site of the enzymes. The binding of the inhibitor may overlap the catalytic site completely or partially. The degree of overlapping is characteristic of the kind of acid proteinases."}
{"id": "PMID:238605", "title": "Purification and partial characterization of a collagenolytic enzyme from Pseudomonas aeruginosa.", "content": "A proteinase from Pseudomonas aeruginosa exhibiting collagenolytic activity was purified 1575-fold with a recovery of 24% by use of chemical and chromatographic technics. The enzyme preparation appeared to be homogeneous when subjected to chromatographic, electrophoretic and ultracentrifugational analyses. A standard state sedimentation coefficient of 2.10 S was calculated and further analyses indicated that the enzyme had a molecular weight of 17 500 and dimerizes under certain conditions to yield an apparent molecular weight of 34 000. In addition to insoluble collagen, the enzyme catalyzed the hydrolysis of congocoll, azocoll, soluble collagen and casein, but did not attack orcein-elastin, azoalbumin, p-toluene eulfonyl-L-arginine methyl ester, benzoyl-L-tyrosine ethyl ester, and the hexapeptide N-benzyloxycarbonyl-glycyl-L-prolyglycylglycyl-L-prolyl-L-alanine. Enzymatic activity against congocoll was 6-fold greater at pH 7.5 in Tris with HCl than in phosphate buffer at the same ionic strength. Cobalt, and to a lesser extent, Zn2+ appeared to activate the enzyme, especially in phosphate buffer. NcCN and p-chloromercuribenzoate did not appreciably inhibit enzyme activity, while (NH4)2 SO4, EDTA and cysteine displayed a significant inhibitory effect under certain conditions.", "contents": "Purification and partial characterization of a collagenolytic enzyme from Pseudomonas aeruginosa. A proteinase from Pseudomonas aeruginosa exhibiting collagenolytic activity was purified 1575-fold with a recovery of 24% by use of chemical and chromatographic technics. The enzyme preparation appeared to be homogeneous when subjected to chromatographic, electrophoretic and ultracentrifugational analyses. A standard state sedimentation coefficient of 2.10 S was calculated and further analyses indicated that the enzyme had a molecular weight of 17 500 and dimerizes under certain conditions to yield an apparent molecular weight of 34 000. In addition to insoluble collagen, the enzyme catalyzed the hydrolysis of congocoll, azocoll, soluble collagen and casein, but did not attack orcein-elastin, azoalbumin, p-toluene eulfonyl-L-arginine methyl ester, benzoyl-L-tyrosine ethyl ester, and the hexapeptide N-benzyloxycarbonyl-glycyl-L-prolyglycylglycyl-L-prolyl-L-alanine. Enzymatic activity against congocoll was 6-fold greater at pH 7.5 in Tris with HCl than in phosphate buffer at the same ionic strength. Cobalt, and to a lesser extent, Zn2+ appeared to activate the enzyme, especially in phosphate buffer. NcCN and p-chloromercuribenzoate did not appreciably inhibit enzyme activity, while (NH4)2 SO4, EDTA and cysteine displayed a significant inhibitory effect under certain conditions."}
{"id": "PMID:238606", "title": "The effect of Mg2+ and chelating agents on intermediary steps of the reaction ofNa+,K+-activated ATPase.", "content": "(1) It has been investigated how varying concentrations of free magnesium with and without EDTA influence the properties of the phospho-enzyme formed in the presence of sodium by the (Na+ plus K+)-activated enzyme system. (2) The phospho-enzyme formed in the presence of sodium and a high concentration of free magnesium has the same rate of (a) spontaneous dephosphorylation, (b) dephosphorylation after addition of potassium, and (c) dephosphorylation after addition of ADP, as a phospho-enzyme formed in the presence of sodium and a low concentration of magnesium. (3) With sodium and a given concentration of free magnesium, high or low, EDTA present during formation of the phospho-enzyme leads to a decrease in the rate of (a) spontaneous dephosphorylation, and (b) dephosphorylation after addition of potassium to the phospho-enzyme. (4) The rate of dephosphorylation after addition of ADP to phospho-enzyme formed without and with EDTA is the same. But as the rate of spontaneous dephosphorylation is lower with EDTA than without, ADP gives a higher increase in the rate of dephosphorylation of phospho-enzyme formed with EDTA than without. (5) The experiments thus show that the reported different sensitivity towards potassium and ADP of phospho-enzyme formed in the presence of a low and high concentration of free magnesium, respectively, is due to the EDTA used to decrease the free magnesium concentration and not to the decrease in the free magnesium as such.", "contents": "The effect of Mg2+ and chelating agents on intermediary steps of the reaction ofNa+,K+-activated ATPase. (1) It has been investigated how varying concentrations of free magnesium with and without EDTA influence the properties of the phospho-enzyme formed in the presence of sodium by the (Na+ plus K+)-activated enzyme system. (2) The phospho-enzyme formed in the presence of sodium and a high concentration of free magnesium has the same rate of (a) spontaneous dephosphorylation, (b) dephosphorylation after addition of potassium, and (c) dephosphorylation after addition of ADP, as a phospho-enzyme formed in the presence of sodium and a low concentration of magnesium. (3) With sodium and a given concentration of free magnesium, high or low, EDTA present during formation of the phospho-enzyme leads to a decrease in the rate of (a) spontaneous dephosphorylation, and (b) dephosphorylation after addition of potassium to the phospho-enzyme. (4) The rate of dephosphorylation after addition of ADP to phospho-enzyme formed without and with EDTA is the same. But as the rate of spontaneous dephosphorylation is lower with EDTA than without, ADP gives a higher increase in the rate of dephosphorylation of phospho-enzyme formed with EDTA than without. (5) The experiments thus show that the reported different sensitivity towards potassium and ADP of phospho-enzyme formed in the presence of a low and high concentration of free magnesium, respectively, is due to the EDTA used to decrease the free magnesium concentration and not to the decrease in the free magnesium as such."}
{"id": "PMID:238607", "title": "Inhibition of horse muscle acylphosphatase by pyridoxal 5'-phosphate.", "content": "It has been shown that horse muscle acylphosphatase is inhibited by pyridoxal 5'-phosphate and that the inhibition is pH dependent, reversible and competitive with respect to substrate binding. Spectral analysis on the EI complex demonstrates the presence of a Schiff base. Reduction of the pyridoxal 5'-phosphate-inhibited enzyme with sodium borohydride, followed by amino acid analysis, produces a diminution of the free lysine peak and the appearance of a new peak corresponding to epsilon-pyridoxyllysine. The results suggest that there is at least one NH2-lysyl residue of horse muscle acylphosphatase at or near the active site of the enzyme.", "contents": "Inhibition of horse muscle acylphosphatase by pyridoxal 5'-phosphate. It has been shown that horse muscle acylphosphatase is inhibited by pyridoxal 5'-phosphate and that the inhibition is pH dependent, reversible and competitive with respect to substrate binding. Spectral analysis on the EI complex demonstrates the presence of a Schiff base. Reduction of the pyridoxal 5'-phosphate-inhibited enzyme with sodium borohydride, followed by amino acid analysis, produces a diminution of the free lysine peak and the appearance of a new peak corresponding to epsilon-pyridoxyllysine. The results suggest that there is at least one NH2-lysyl residue of horse muscle acylphosphatase at or near the active site of the enzyme."}
{"id": "PMID:238608", "title": "The oxidation of cytochrome c peroxidase by hydrogen peroxide. Characterization of products.", "content": "H2O2 reacts with cytochrome c peroxidase in a variety of ways. The initial reaction produces cytochrome c peroxidase Compound I. If more than a 10-fold excess of H2O2 is added to the enzyme, a portion of the H2O2 will react with Compound I to produce molecular oxygen. The remainder oxidizes the heme group and various amino acid residues in the protein. If less than a 10-fold excess of H2O2 is added to the enzyme, essentially all the H2O2 is utilized by oxidation of amino acid residues in the protein. The oxidation of the amino acid residues by H2O2 substantially modifies the reactivity of cytochrome c peroxidase. The modification of reactivity could be the direct result of amino acid oxidation or an indirect result caused by a perturbation of the protein structure at the active site. The products oxidized at pH 8 lose their ability to react with H2O2. The products oxidized at pH4 react with H2O2 but their reactivity toward Fe(CN)4-6 is substantially reduced.", "contents": "The oxidation of cytochrome c peroxidase by hydrogen peroxide. Characterization of products. H2O2 reacts with cytochrome c peroxidase in a variety of ways. The initial reaction produces cytochrome c peroxidase Compound I. If more than a 10-fold excess of H2O2 is added to the enzyme, a portion of the H2O2 will react with Compound I to produce molecular oxygen. The remainder oxidizes the heme group and various amino acid residues in the protein. If less than a 10-fold excess of H2O2 is added to the enzyme, essentially all the H2O2 is utilized by oxidation of amino acid residues in the protein. The oxidation of the amino acid residues by H2O2 substantially modifies the reactivity of cytochrome c peroxidase. The modification of reactivity could be the direct result of amino acid oxidation or an indirect result caused by a perturbation of the protein structure at the active site. The products oxidized at pH 8 lose their ability to react with H2O2. The products oxidized at pH4 react with H2O2 but their reactivity toward Fe(CN)4-6 is substantially reduced."}
{"id": "PMID:238609", "title": "A kinetic study of the endogenous reduction of the oxidized sites in the primary cytochrome c peroxidase-hydrogen peroxide compound.", "content": "The primatry compound formed in the reaction between H2O2 and cytochrome c peroxidase is oxidized two equivalents above the native enzyme. The two oxidized sites are thought to be an Fe(IV) and an amino acid radical. In the absence of oxidizable substrate, the Fe(IV) and radical sites decay by apparent first-order processes but at different rates. It is likely that the decay involves both intra- and intermolecular electron-transfer reactions. The reduction of the Fe(IV) site depends upon the pH with a minimum reduction rate of 2.9-10(-5)s(-1) at pH 6. At pH 4 and 6, the reduction of the Fe(IV) site is facilitated by prior oxidation of amino acid residues in the protein.", "contents": "A kinetic study of the endogenous reduction of the oxidized sites in the primary cytochrome c peroxidase-hydrogen peroxide compound. The primatry compound formed in the reaction between H2O2 and cytochrome c peroxidase is oxidized two equivalents above the native enzyme. The two oxidized sites are thought to be an Fe(IV) and an amino acid radical. In the absence of oxidizable substrate, the Fe(IV) and radical sites decay by apparent first-order processes but at different rates. It is likely that the decay involves both intra- and intermolecular electron-transfer reactions. The reduction of the Fe(IV) site depends upon the pH with a minimum reduction rate of 2.9-10(-5)s(-1) at pH 6. At pH 4 and 6, the reduction of the Fe(IV) site is facilitated by prior oxidation of amino acid residues in the protein."}
{"id": "PMID:238610", "title": "Evidence for the existence of a low spin complex in acidic methemoglobin: its structure and formation.", "content": "By means of electron spin resonance and magneto-optical rotation, specific low spin complexes in acidic methemoglobin are obtained. The formation of these complexes is explained by a specific stereochemical arrangement of the distal histidine in the absence of allosteric effectors inducing the formation of a low spin ligand at room temperature. At low temperature, however, the distal histidine is directly bound to the heme iron. As the formation of the low spin complexes depends on allosteric effectors it is suggested that via the distal histidine the affinity of heme iron ligands is modified.", "contents": "Evidence for the existence of a low spin complex in acidic methemoglobin: its structure and formation. By means of electron spin resonance and magneto-optical rotation, specific low spin complexes in acidic methemoglobin are obtained. The formation of these complexes is explained by a specific stereochemical arrangement of the distal histidine in the absence of allosteric effectors inducing the formation of a low spin ligand at room temperature. At low temperature, however, the distal histidine is directly bound to the heme iron. As the formation of the low spin complexes depends on allosteric effectors it is suggested that via the distal histidine the affinity of heme iron ligands is modified."}
{"id": "PMID:238611", "title": "Recombination of carbon monoxide with hemoglobin after flash photolysis of the carboxyderivative in mixed solvents at subzero temperature.", "content": "The kinetics of recombination of carbon monoxide to hemoglobin produced by total flash photolysis of its carboxyderivative are studied at low temperatures (down to --55 degrees C) in mixed hydroalcoholic solvents. The rates are found to be different in two solvents used, namely ethylene glycol/buffer and methanol/buffer; for the former, the rates at subzero temperatures are simply explained by cooling and are consistent with the activation energy as measured in aqueous solution, while those in methanol/buffer show evidence of a specific solvent effect. Values are reported for the rate constants and activation energies in the two solvents.", "contents": "Recombination of carbon monoxide with hemoglobin after flash photolysis of the carboxyderivative in mixed solvents at subzero temperature. The kinetics of recombination of carbon monoxide to hemoglobin produced by total flash photolysis of its carboxyderivative are studied at low temperatures (down to --55 degrees C) in mixed hydroalcoholic solvents. The rates are found to be different in two solvents used, namely ethylene glycol/buffer and methanol/buffer; for the former, the rates at subzero temperatures are simply explained by cooling and are consistent with the activation energy as measured in aqueous solution, while those in methanol/buffer show evidence of a specific solvent effect. Values are reported for the rate constants and activation energies in the two solvents."}
{"id": "PMID:238612", "title": "Analytical isotachophoresis in capillary tubes. Analysis of hemoglobin, hemiglobin cyanide and isoelectric fractions of hemiglobin cyanide.", "content": "The zone stabilization in capillary isotachophoresis in the water phase has been improved by methylcellulose so that proteins can be analysed. Hemoglobin and hemiglobin cyanide samples were studied as model systems. Ampholine carrier ampholytes were used as spacers, enhancing the detection of the different components. The optimal amounts of Ampholine, however, were found to be much smaller than in most of the previously published reports. Linear relationships were found between the zone lengths and sample amounts, including spacers. The separations were reproducible and reached the isotachophoretic steady state. The hemiglobin cyanide was fractionated by isoelectric focusing. The four main fractions were then analyzed by capillary isotachophoresis and shown to be heterogeneous in mobility with a pH of 7.5 in the leading electrolyte. The component zones of the total hemiglobin cyanide sample were all identified in relation to the isotachophoretic components of the isoelectric fractions. The total analysis time was in average 30-40 min. The sample amounts were about 40 mug protein in each experiment with very small Ampholine volumes, 25-100 nl 40% (w/v).", "contents": "Analytical isotachophoresis in capillary tubes. Analysis of hemoglobin, hemiglobin cyanide and isoelectric fractions of hemiglobin cyanide. The zone stabilization in capillary isotachophoresis in the water phase has been improved by methylcellulose so that proteins can be analysed. Hemoglobin and hemiglobin cyanide samples were studied as model systems. Ampholine carrier ampholytes were used as spacers, enhancing the detection of the different components. The optimal amounts of Ampholine, however, were found to be much smaller than in most of the previously published reports. Linear relationships were found between the zone lengths and sample amounts, including spacers. The separations were reproducible and reached the isotachophoretic steady state. The hemiglobin cyanide was fractionated by isoelectric focusing. The four main fractions were then analyzed by capillary isotachophoresis and shown to be heterogeneous in mobility with a pH of 7.5 in the leading electrolyte. The component zones of the total hemiglobin cyanide sample were all identified in relation to the isotachophoretic components of the isoelectric fractions. The total analysis time was in average 30-40 min. The sample amounts were about 40 mug protein in each experiment with very small Ampholine volumes, 25-100 nl 40% (w/v)."}
{"id": "PMID:238613", "title": "The luminescence properties of concanavalin A.", "content": "1. The luminescence properties of native concanavalin A, both at room temperature and at 77 degrees K, are similar to those of other proteins containing tyrosine and tryptophan. 2. Binding of methyl alpha-D-glucopyranoside to concanavalin A causes a slight reduction of its fluorescence at room temperature. 3. Removal of Mn2+ and Ca2+ ions from concanavalin A causes a small increase in its fluoresence. The fluorescence: phosphorescence ratio and phosphorescence lifetime of apo-concanavalin A are similar to those of tryptophan. 4. Denaturation of concanavalin A by urea and by guanidine hydrochloride apparently takes place in two stages. Apo-concanavalin A is more easily denatured than the native molecule, but concavalin A combined with methyl alpha-D-glucopyranoside is more resistant to denaturation. 5. The luminescence properties of concanavalin A are pH-dependent. 6. The results have been interpreted in terms of the known structure and properties of concanavalin A.", "contents": "The luminescence properties of concanavalin A. 1. The luminescence properties of native concanavalin A, both at room temperature and at 77 degrees K, are similar to those of other proteins containing tyrosine and tryptophan. 2. Binding of methyl alpha-D-glucopyranoside to concanavalin A causes a slight reduction of its fluorescence at room temperature. 3. Removal of Mn2+ and Ca2+ ions from concanavalin A causes a small increase in its fluoresence. The fluorescence: phosphorescence ratio and phosphorescence lifetime of apo-concanavalin A are similar to those of tryptophan. 4. Denaturation of concanavalin A by urea and by guanidine hydrochloride apparently takes place in two stages. Apo-concanavalin A is more easily denatured than the native molecule, but concavalin A combined with methyl alpha-D-glucopyranoside is more resistant to denaturation. 5. The luminescence properties of concanavalin A are pH-dependent. 6. The results have been interpreted in terms of the known structure and properties of concanavalin A."}
{"id": "PMID:238614", "title": "The low-temperature luminescence properties of bovine alpha-lactalbumin.", "content": "The luminescence of bovine alpha-lactalbumin at 77 K has been studied and compared with that of lysozyme. Alpha-Lactalbumin has several unusual properties, including a fluorescence spectrum showing vibrational fine structure, an abnormal phosphorescence spectrum, a high fluorescence: phosphorescence ratio and an abnormal phosphorescence decay. These properties are largely due to the proximity of tryptophan residues to disulphide bonds. Reduction of all these bonds causes considerable changes in alpha-lactalbumin luminescence, as does denaturation in acid solution. Reduction of a single labile disulphide bond has little effect, and the properties of alpha-lactalbumin III, a variant lacking one disulphide bond and one trypotophan residue, are similar to those of the normal protein. Several differences between alpha-lactalbumin and lysozyme are reported. The results support the suggestion that the two tryptophan residues found in the active site cleft of alpha-lactalbumin may be largely responsible for its luminescence.", "contents": "The low-temperature luminescence properties of bovine alpha-lactalbumin. The luminescence of bovine alpha-lactalbumin at 77 K has been studied and compared with that of lysozyme. Alpha-Lactalbumin has several unusual properties, including a fluorescence spectrum showing vibrational fine structure, an abnormal phosphorescence spectrum, a high fluorescence: phosphorescence ratio and an abnormal phosphorescence decay. These properties are largely due to the proximity of tryptophan residues to disulphide bonds. Reduction of all these bonds causes considerable changes in alpha-lactalbumin luminescence, as does denaturation in acid solution. Reduction of a single labile disulphide bond has little effect, and the properties of alpha-lactalbumin III, a variant lacking one disulphide bond and one trypotophan residue, are similar to those of the normal protein. Several differences between alpha-lactalbumin and lysozyme are reported. The results support the suggestion that the two tryptophan residues found in the active site cleft of alpha-lactalbumin may be largely responsible for its luminescence."}
{"id": "PMID:238615", "title": "Fluorescence polarization studies on the conformational transition of bovine plasma albumin in acidic solutions.", "content": "The acid-induced isomerization (the N-F transition) and expansion of bovine plasma albumin were studied by measuring fluorescence polarization and lifetime of the excited state of tryptophyl fluorophors. Most of the changes (decreases) in the reciprocal of fluorescence polarization and lifetime of the excited state correlated exactly with the N-F1 transition and/or the initial part of the N-F transition. These findings suggest that though the N-F transition is the cooperative pH-dependent conformational transition, the N-F transition clearly involves an intermediate step, such as the N-F1 and F1-F2 transitions. Rotational relaxation times for the N- and F-forms obtained by Perrin plot of tryptophyl fluorescence polarization were approximately 75 and 120-180 ns, respectively. The unexpected short rotational relaxation time of 75 ns of the N-form might be due to the rotational freedom of the tryptophyl side chain itself and/or of small flexible loci where tryptophyl fluorophors attach.", "contents": "Fluorescence polarization studies on the conformational transition of bovine plasma albumin in acidic solutions. The acid-induced isomerization (the N-F transition) and expansion of bovine plasma albumin were studied by measuring fluorescence polarization and lifetime of the excited state of tryptophyl fluorophors. Most of the changes (decreases) in the reciprocal of fluorescence polarization and lifetime of the excited state correlated exactly with the N-F1 transition and/or the initial part of the N-F transition. These findings suggest that though the N-F transition is the cooperative pH-dependent conformational transition, the N-F transition clearly involves an intermediate step, such as the N-F1 and F1-F2 transitions. Rotational relaxation times for the N- and F-forms obtained by Perrin plot of tryptophyl fluorescence polarization were approximately 75 and 120-180 ns, respectively. The unexpected short rotational relaxation time of 75 ns of the N-form might be due to the rotational freedom of the tryptophyl side chain itself and/or of small flexible loci where tryptophyl fluorophors attach."}
{"id": "PMID:238616", "title": "Circular dichroism of cephalopod rhodopsin and its intermediates in the bleaching and photoregeneration process.", "content": "In the bleaching process of cephalopod rhodopsin, a new intermediate was found in the conversion process from lumirhodopsin to metarhodopsin. This intermediate of octopus has an absorption peak at about 475 nm and has been named as M475. The circular dichroism value of M475 is too small to be evaluated. On the other hand, lumirhodopsin shows a negative CD at 470 nm, a positive CD at 350 nm and a large positive CD band with three peaks at 280, 287 and 295 nm. Such a large CD band in the ultraviolet region is not observed in rhodopsin, M475 and metarhodopsin. This CD seems to be mainly due to tryptophan and tyrosine residues restricted in free rotation in the protein moiety of lumirhodopsin. The intermediate in the photoregeneration process of cephalopod rhodopsin, P380, has a positive CD band at the main peak, 380 nm, and also a large positive CD band in the ultraviolet region like lumirhodopsin.", "contents": "Circular dichroism of cephalopod rhodopsin and its intermediates in the bleaching and photoregeneration process. In the bleaching process of cephalopod rhodopsin, a new intermediate was found in the conversion process from lumirhodopsin to metarhodopsin. This intermediate of octopus has an absorption peak at about 475 nm and has been named as M475. The circular dichroism value of M475 is too small to be evaluated. On the other hand, lumirhodopsin shows a negative CD at 470 nm, a positive CD at 350 nm and a large positive CD band with three peaks at 280, 287 and 295 nm. Such a large CD band in the ultraviolet region is not observed in rhodopsin, M475 and metarhodopsin. This CD seems to be mainly due to tryptophan and tyrosine residues restricted in free rotation in the protein moiety of lumirhodopsin. The intermediate in the photoregeneration process of cephalopod rhodopsin, P380, has a positive CD band at the main peak, 380 nm, and also a large positive CD band in the ultraviolet region like lumirhodopsin."}
{"id": "PMID:238617", "title": "In vivo and in vitro aging of collagen examined using an isometric melting technique.", "content": "1. In vivo and in vitro aging of tendon from rat tail, kangaroo tail and human wrist tendon was examined by the technique of isometric melting, in physiological saline. 2. For all these collagens, two mechanisms of structure stabilisation can be distinguished in the melting curves. One of these involves co-valent cross-linking as judged by its increasing stability to heat and acid pH, while the second appears to involve only secondary interactions. 3. The time rate of the first process is slow in vivo; rat tendon up to 2 years does not show it, but it is present in 6-year-old human tendon. However, its in vitro rate is markedly dependent upon the free oxygen content of the physiological saline. At an oxygen concentration of 300 nmol/ml, the in vitro aging rate is about 30 times the in vivo rate for rat tail tendon, and about 20 times for both kangaroo tail tendon and human wrist tendon. At a concentration of 60 nmol/ml (which is about the same as normal arteriovenous blood difference) in vitro aging proceeds close to the in vivo rate.", "contents": "In vivo and in vitro aging of collagen examined using an isometric melting technique. 1. In vivo and in vitro aging of tendon from rat tail, kangaroo tail and human wrist tendon was examined by the technique of isometric melting, in physiological saline. 2. For all these collagens, two mechanisms of structure stabilisation can be distinguished in the melting curves. One of these involves co-valent cross-linking as judged by its increasing stability to heat and acid pH, while the second appears to involve only secondary interactions. 3. The time rate of the first process is slow in vivo; rat tendon up to 2 years does not show it, but it is present in 6-year-old human tendon. However, its in vitro rate is markedly dependent upon the free oxygen content of the physiological saline. At an oxygen concentration of 300 nmol/ml, the in vitro aging rate is about 30 times the in vivo rate for rat tail tendon, and about 20 times for both kangaroo tail tendon and human wrist tendon. At a concentration of 60 nmol/ml (which is about the same as normal arteriovenous blood difference) in vitro aging proceeds close to the in vivo rate."}
{"id": "PMID:238618", "title": "State and reactivity of tryptophyl residues in two bacterial proteases from Sorangium sp.", "content": "The state and reactivity of tryptophyl residues in two proteolytic enzymes from Sorangium sp. were investigated by means of the following methods: spectrophotometric oxidation of tryptophans with N-bromosuccinimide, 2-hydroxy-5-nitrobenzyl bromide, and H2O2 in dioxane, optical rotatory dispersion, ultraviolet difference spectrophotometry, solvent perturbation and viscosity measurements. Out of two tryptophyl residues/molecule of alpha-lytic protease, one appears to be completely buried, while the other seems to be exposed. None of these two residues seem to be responsible for the activity of the enzyme. The beta-lytic protease undergoes an irreversible conformational transition between pH 5.0 and 3.5. Out of total four tryptophyl residues/molecule, only one is fully exposed at neutral pH. The other three are gradually exposed in the pH transition region. The degree of exposure and the dimensions of \"cavities\" shielding tryptophyl residues were estimated. The tryptophyl residues of of beta-lytic protease do not seem to participate in substrate binding or the active site; they are rather one of the determinants of the conformational state of the enzyme.", "contents": "State and reactivity of tryptophyl residues in two bacterial proteases from Sorangium sp. The state and reactivity of tryptophyl residues in two proteolytic enzymes from Sorangium sp. were investigated by means of the following methods: spectrophotometric oxidation of tryptophans with N-bromosuccinimide, 2-hydroxy-5-nitrobenzyl bromide, and H2O2 in dioxane, optical rotatory dispersion, ultraviolet difference spectrophotometry, solvent perturbation and viscosity measurements. Out of two tryptophyl residues/molecule of alpha-lytic protease, one appears to be completely buried, while the other seems to be exposed. None of these two residues seem to be responsible for the activity of the enzyme. The beta-lytic protease undergoes an irreversible conformational transition between pH 5.0 and 3.5. Out of total four tryptophyl residues/molecule, only one is fully exposed at neutral pH. The other three are gradually exposed in the pH transition region. The degree of exposure and the dimensions of \"cavities\" shielding tryptophyl residues were estimated. The tryptophyl residues of of beta-lytic protease do not seem to participate in substrate binding or the active site; they are rather one of the determinants of the conformational state of the enzyme."}
{"id": "PMID:238619", "title": "Salt effects on the denaturation of DNA. IV. A calorimetric study of the helix-coil conversion of the alternating copolymer poly[d(A-T)].", "content": "The enthalpy deltaH, entropy deltaS, and the temperature Tm of the conformational transition of poly[d (A-T)] from the ordered to the randomly oriented state have been determined at pH 6.8 with the help of an adiabatic differential scanning calorimeter in Na2SO4 solutions of increasing ionic strength. Spectrophotometric denaturation experiments supplemented the calorimetric measurements. All thermodynamic parameters were found to vary strongly with salt concentration: both deltaH and Tm increase linearly with the logarithm of the mean molal activity alpha plus or minus of Na2SO4. However, whereas the dependence of Tm on salt activity remains linear over the entire salt concentration range employed deltaH decreases abruptly in the most concentrated Na2SO4 solutions. The entropy of melting changes with salt concentration in a pattern similar to that displayed by deltaH. The data on deltaH as well as data derived from the maximum slopes of the calorimetric heat denaturation curves were used to calculate the cooperative length Lh, the stacking free energy epsilon, and the cooperativity parameter sigma of poly[d(A-T)] as a function of ionic strength. Lh decreases with increasing salt concentration whereas sigma increases. Epsilon assumes more positive values with increasing salt molality. These changes then are in agreement with the generally held belief that an increase in salt concentration leads to an increase in the \"loop\" content of the copolymer.", "contents": "Salt effects on the denaturation of DNA. IV. A calorimetric study of the helix-coil conversion of the alternating copolymer poly[d(A-T)]. The enthalpy deltaH, entropy deltaS, and the temperature Tm of the conformational transition of poly[d (A-T)] from the ordered to the randomly oriented state have been determined at pH 6.8 with the help of an adiabatic differential scanning calorimeter in Na2SO4 solutions of increasing ionic strength. Spectrophotometric denaturation experiments supplemented the calorimetric measurements. All thermodynamic parameters were found to vary strongly with salt concentration: both deltaH and Tm increase linearly with the logarithm of the mean molal activity alpha plus or minus of Na2SO4. However, whereas the dependence of Tm on salt activity remains linear over the entire salt concentration range employed deltaH decreases abruptly in the most concentrated Na2SO4 solutions. The entropy of melting changes with salt concentration in a pattern similar to that displayed by deltaH. The data on deltaH as well as data derived from the maximum slopes of the calorimetric heat denaturation curves were used to calculate the cooperative length Lh, the stacking free energy epsilon, and the cooperativity parameter sigma of poly[d(A-T)] as a function of ionic strength. Lh decreases with increasing salt concentration whereas sigma increases. Epsilon assumes more positive values with increasing salt molality. These changes then are in agreement with the generally held belief that an increase in salt concentration leads to an increase in the \"loop\" content of the copolymer."}
{"id": "PMID:238620", "title": "Specific conversion of s4 U to U in Escherichia coli tRNA by iodate oxidation.", "content": "The minor nucleoside 4-thiouridine in Escherichia coli tRNA is transformed selectively to uridine by iodate oxidation at acidic pH. The four major nucleotides were found to be inert under these conditions. The iodate oxidation appears to be more specific than the previous conversion methods reported, and has the advantage that it does not affect the chargeability of most tRNA.", "contents": "Specific conversion of s4 U to U in Escherichia coli tRNA by iodate oxidation. The minor nucleoside 4-thiouridine in Escherichia coli tRNA is transformed selectively to uridine by iodate oxidation at acidic pH. The four major nucleotides were found to be inert under these conditions. The iodate oxidation appears to be more specific than the previous conversion methods reported, and has the advantage that it does not affect the chargeability of most tRNA."}
{"id": "PMID:238621", "title": "Puridication and properties of an intracellular ribonuclease from Candida lipolytica.", "content": "1. A ribonuclease (RNAase CL) (EC 3.1.4.23, ribonucleate 3'-oligonucleotide hydrolase) was extracted by EDTA/acetate buffer, pH 5.6 from acetonedried cells of Candida lipolytica and purified 1350-fold by acetone and (NH4)2SO4 fractionation, DEAE-cellulose and DEAE-Sephadex chromatography. 2. RNAase CL is an acidic protein having an isoelectric point of 4.2, and an approximate molecular weight of 32 000. 3. Optimal pH and temperature for the enzyme were 6.0 and 60 degrees C, respectively. It is stable at neutral pH up to 50 degrees C. At 64 degrees C for 30 min, 95, 49 and 64% inactivation of the enzyme occurred at pH values 4.2, 6.6 and 10.0, respectively. 4. RNAase CL inhibited by Zn2+ and Cu2+, sulfhydryl reactants and by high concentration of salts, but not by chelating agents. 5. RNAase CL degraded ribosomal RNA, transfer RNA, polyadenylic acid, polycytidylic acid and polyuridylic acid into acid-soluble nucleotides. Among the synthetic homopolymers, polycytidylic acid was most rapidly degraded. Polyguanylic acid and duplexes of synthetic homopolymers were less sensitive. DNA was not attacked. Specificity studies showed that RNAase CL preferentially cleaves pC-purine bonds. 6. Digestion of poly (C) by RNAase CL resulted in the liberation of cyclic 2',3'-CPM from the start of the reaction with no observable formation of intermediate oligonucleotides. This suggests that the enzyme depolymerizes by an exonucleolytic mechanism.", "contents": "Puridication and properties of an intracellular ribonuclease from Candida lipolytica. 1. A ribonuclease (RNAase CL) (EC 3.1.4.23, ribonucleate 3'-oligonucleotide hydrolase) was extracted by EDTA/acetate buffer, pH 5.6 from acetonedried cells of Candida lipolytica and purified 1350-fold by acetone and (NH4)2SO4 fractionation, DEAE-cellulose and DEAE-Sephadex chromatography. 2. RNAase CL is an acidic protein having an isoelectric point of 4.2, and an approximate molecular weight of 32 000. 3. Optimal pH and temperature for the enzyme were 6.0 and 60 degrees C, respectively. It is stable at neutral pH up to 50 degrees C. At 64 degrees C for 30 min, 95, 49 and 64% inactivation of the enzyme occurred at pH values 4.2, 6.6 and 10.0, respectively. 4. RNAase CL inhibited by Zn2+ and Cu2+, sulfhydryl reactants and by high concentration of salts, but not by chelating agents. 5. RNAase CL degraded ribosomal RNA, transfer RNA, polyadenylic acid, polycytidylic acid and polyuridylic acid into acid-soluble nucleotides. Among the synthetic homopolymers, polycytidylic acid was most rapidly degraded. Polyguanylic acid and duplexes of synthetic homopolymers were less sensitive. DNA was not attacked. Specificity studies showed that RNAase CL preferentially cleaves pC-purine bonds. 6. Digestion of poly (C) by RNAase CL resulted in the liberation of cyclic 2',3'-CPM from the start of the reaction with no observable formation of intermediate oligonucleotides. This suggests that the enzyme depolymerizes by an exonucleolytic mechanism."}
{"id": "PMID:238622", "title": "Histone-like protein in the prokaryote Thermoplasma acidophilum.", "content": "The DNA of the prokaryote Thermoplasma acidophilum is associated with a histone-like protein that has the following properties: it has a high content (23%) of basic amino acids, is positively charged at neutral pH, is soluble in acid, and can stabilize DNA against thermal denaturation. In polyacrylamide gel electrophoresis, in the presence of either sodium dodecylsulfate or urea, it migrates at the same rate as histone IV (F2a1) of calf thymus. The amino acid composition, however, it unusually rich in the amides of acidic amino acids (16-20%), and it does not appear to be closely homologous to any of the classes of eukaryotic histones. Escherichia coli DNA, on the other hand, was associated with no detectable acid-soluble proteins, and the nucleoprotein thermally denatured at a lower temperature than pure DNA.", "contents": "Histone-like protein in the prokaryote Thermoplasma acidophilum. The DNA of the prokaryote Thermoplasma acidophilum is associated with a histone-like protein that has the following properties: it has a high content (23%) of basic amino acids, is positively charged at neutral pH, is soluble in acid, and can stabilize DNA against thermal denaturation. In polyacrylamide gel electrophoresis, in the presence of either sodium dodecylsulfate or urea, it migrates at the same rate as histone IV (F2a1) of calf thymus. The amino acid composition, however, it unusually rich in the amides of acidic amino acids (16-20%), and it does not appear to be closely homologous to any of the classes of eukaryotic histones. Escherichia coli DNA, on the other hand, was associated with no detectable acid-soluble proteins, and the nucleoprotein thermally denatured at a lower temperature than pure DNA."}
{"id": "PMID:238623", "title": "Effect of hydrogen ion concentration on energy metabolism in pig platelets.", "content": "Respiration and glycolysis of pig platelets suspended in a dialyzed plasma were studied at various hydrogen ion concentrations. Respiration of platelets was high at acidic pH and decreased at physiological pH. This pH profile may not be attributed to properties of mitochondria, since the respiratory rate of mitochondria prepared from platelets was maximal at physiological pH. A low respiratory rate at physiological pH seemed to be attributable to depression of respiration by glycolysis, since the addition of glucose further depressed the rate. The Crabtree effect was more prominent at alkaline ph. glycolysis increased with an increase in the pH of the plasma, contrary to oxygen comsumption. The Pasteur effect was less prominent at alkaline pH. The effect of pH on lactate production by the cytosol fraction of platelets was similar to that of whole platelets. The glycolytic intermediate pattern showed that phosphofructolinase was the committed step. Both ATP concentration and ATP formation calculated from respiratory and glycolytic rates were constant at various pH values. These observations may indicate that the pH primarily affects platelet glycolysis at the phosphofructokinase step and the respiration is secondarily controlled by glycolysis.", "contents": "Effect of hydrogen ion concentration on energy metabolism in pig platelets. Respiration and glycolysis of pig platelets suspended in a dialyzed plasma were studied at various hydrogen ion concentrations. Respiration of platelets was high at acidic pH and decreased at physiological pH. This pH profile may not be attributed to properties of mitochondria, since the respiratory rate of mitochondria prepared from platelets was maximal at physiological pH. A low respiratory rate at physiological pH seemed to be attributable to depression of respiration by glycolysis, since the addition of glucose further depressed the rate. The Crabtree effect was more prominent at alkaline ph. glycolysis increased with an increase in the pH of the plasma, contrary to oxygen comsumption. The Pasteur effect was less prominent at alkaline pH. The effect of pH on lactate production by the cytosol fraction of platelets was similar to that of whole platelets. The glycolytic intermediate pattern showed that phosphofructolinase was the committed step. Both ATP concentration and ATP formation calculated from respiratory and glycolytic rates were constant at various pH values. These observations may indicate that the pH primarily affects platelet glycolysis at the phosphofructokinase step and the respiration is secondarily controlled by glycolysis."}
{"id": "PMID:238624", "title": "Comparative aspects of the calcium-sensitive photoproteins aequorin and obelin.", "content": "1. The calcium-dependency of the process of light emission has been investigated for the photoproteins aequorin and obelin. 2. The experimental curves of light production, expressed as a percentage of the maximal rate of utilisation, versus pCa are accurately predicted by the cooperative action of at least 2Ca-2+ for aequorin and at least 3Ca-2+ for obelin. 3. At low total monovalent cation concentrations, a pH change from 6.8 to 7.1 shifts the light production vs pCa curve by approx. 0.2 pCa units to the right for aequorin, while that for obelin is shifted by some 0.37 pCa units. 4. Other monovalent cations, such as Na+ are able to compete with Ca-2+ for the active sites of aequorin and also shift the light production vs pCa curve to the right. There is no apparent change in the calcium stoichiometry for light production under these conditions. 5. The same calcium stoichiometry for light emission was also obtained for aequorin or obelin in the presence of either unbuffered Ca-2+ solutions or of calcium/EGTA buffers.", "contents": "Comparative aspects of the calcium-sensitive photoproteins aequorin and obelin. 1. The calcium-dependency of the process of light emission has been investigated for the photoproteins aequorin and obelin. 2. The experimental curves of light production, expressed as a percentage of the maximal rate of utilisation, versus pCa are accurately predicted by the cooperative action of at least 2Ca-2+ for aequorin and at least 3Ca-2+ for obelin. 3. At low total monovalent cation concentrations, a pH change from 6.8 to 7.1 shifts the light production vs pCa curve by approx. 0.2 pCa units to the right for aequorin, while that for obelin is shifted by some 0.37 pCa units. 4. Other monovalent cations, such as Na+ are able to compete with Ca-2+ for the active sites of aequorin and also shift the light production vs pCa curve to the right. There is no apparent change in the calcium stoichiometry for light production under these conditions. 5. The same calcium stoichiometry for light emission was also obtained for aequorin or obelin in the presence of either unbuffered Ca-2+ solutions or of calcium/EGTA buffers."}
{"id": "PMID:238625", "title": "Properties and regulation of C-1-fructose-1,6-diphosphatase from spinach chloroplasts.", "content": "Chloroplast fructose diphosphatase (EC 3.1.3.11) was purified according to the procedures of Racker and Schroeder [1] and Buchanan et al. [2] and the properties compared. Neither preparation contained fructose diphosphatase from the cytoplasm. The preparations had similar molecular weights, pH optima, affinites for fructose diphosphate and Mg-2+ and were similarly activated by EDTA, dithiothreitol and cystamine. Mg-2+, fructose diphosphate and dithiothreitol all activate chloroplast fructose diphosphatase more so at suboptimal pH values. The combined effects of these substances under estimated physiological conditions in the chloroplast stroma in the light and in darkness were consistent with almost full activity of the enzyme during illumination but no activity in the dark.", "contents": "Properties and regulation of C-1-fructose-1,6-diphosphatase from spinach chloroplasts. Chloroplast fructose diphosphatase (EC 3.1.3.11) was purified according to the procedures of Racker and Schroeder [1] and Buchanan et al. [2] and the properties compared. Neither preparation contained fructose diphosphatase from the cytoplasm. The preparations had similar molecular weights, pH optima, affinites for fructose diphosphate and Mg-2+ and were similarly activated by EDTA, dithiothreitol and cystamine. Mg-2+, fructose diphosphate and dithiothreitol all activate chloroplast fructose diphosphatase more so at suboptimal pH values. The combined effects of these substances under estimated physiological conditions in the chloroplast stroma in the light and in darkness were consistent with almost full activity of the enzyme during illumination but no activity in the dark."}
{"id": "PMID:238626", "title": "Multichannel microspectrofluorometry for topographic and spectral analysis of NAD(P)H fluorescence in single living cells.", "content": "Starting from a previously described prototype microspectrofluorometer a more versatile apparatus has been developed with rapid optional operation on a topographic mode for the simultaneous multisite evaluation of NAD(P) reduction-reoxidation transients or on a spectral mode for the analysis of natural and exogenous fluorochromes, in single living cells. On the topographic mode, adetailed kinetic analysis of NAD or NAD P-linked dehydrogenases can be made from 50-100 cell points imultaneously via automatic recording of topographic scans upt to 16 times a second, in correlation with microelectrophoretic intracellular inuection of metabolites (e.g. nearly immediate response to glucose 6-phosphate, 20-25 s delay for 6-phosphogluconate). Rapid shifts from topographic to spectral operation make possible the detection of a change in fluorescence intensity at a specific intracellular site and the immediate verification of its nature (NAD(P)H or exogenous fluorochrome) by spectral observations.", "contents": "Multichannel microspectrofluorometry for topographic and spectral analysis of NAD(P)H fluorescence in single living cells. Starting from a previously described prototype microspectrofluorometer a more versatile apparatus has been developed with rapid optional operation on a topographic mode for the simultaneous multisite evaluation of NAD(P) reduction-reoxidation transients or on a spectral mode for the analysis of natural and exogenous fluorochromes, in single living cells. On the topographic mode, adetailed kinetic analysis of NAD or NAD P-linked dehydrogenases can be made from 50-100 cell points imultaneously via automatic recording of topographic scans upt to 16 times a second, in correlation with microelectrophoretic intracellular inuection of metabolites (e.g. nearly immediate response to glucose 6-phosphate, 20-25 s delay for 6-phosphogluconate). Rapid shifts from topographic to spectral operation make possible the detection of a change in fluorescence intensity at a specific intracellular site and the immediate verification of its nature (NAD(P)H or exogenous fluorochrome) by spectral observations."}
{"id": "PMID:238627", "title": "Activation of bovine liver glycerol kinase by ethanol.", "content": "The crystallization of bovine glycerol kinase (ATP:glycerol 3-phosphotransferase EC 2.7.1.30) is reported along with a study on the unusual activation of this enzyme by ethanol. The enzyme was extracted from calf lever andusual activation of this enzyme by ethanol. The enzyme was extracted from calf liver and purified 5900-fold giving crystals with a 5% yield. The kinetics of the enzyme with regard to glycerol and ATP were studied by varying the concentration of one substrate while keeping the other at saturating levels, and the effect of ethanol was observed by adding it at levels of 5% (v/v). Ethanol increased the V in both cases almost 2-fold. The apparent Km of ATP was 3.5 - 10(-6) and was increased to 7.6 - 10(-6) in the presence of ethanol. The apparent Km for glycerol was 3 - 10(-5) and was increased to 12 - 10(-5) when ethanol was added. A number of other alcohols had a similar activating effect except for 1,2-diols which only inhibited the enzyme. These findings are consistent with the explanation that alcohols compete with glycerol (hence also with the glycerophosphate product) for a hydroxy binding site on the enzyme. This leads to more rapid dissociation of the glycerophosphate (i.e. an increase in the steady-state constant, \"k+2\" resulting in an increased V).", "contents": "Activation of bovine liver glycerol kinase by ethanol. The crystallization of bovine glycerol kinase (ATP:glycerol 3-phosphotransferase EC 2.7.1.30) is reported along with a study on the unusual activation of this enzyme by ethanol. The enzyme was extracted from calf lever andusual activation of this enzyme by ethanol. The enzyme was extracted from calf liver and purified 5900-fold giving crystals with a 5% yield. The kinetics of the enzyme with regard to glycerol and ATP were studied by varying the concentration of one substrate while keeping the other at saturating levels, and the effect of ethanol was observed by adding it at levels of 5% (v/v). Ethanol increased the V in both cases almost 2-fold. The apparent Km of ATP was 3.5 - 10(-6) and was increased to 7.6 - 10(-6) in the presence of ethanol. The apparent Km for glycerol was 3 - 10(-5) and was increased to 12 - 10(-5) when ethanol was added. A number of other alcohols had a similar activating effect except for 1,2-diols which only inhibited the enzyme. These findings are consistent with the explanation that alcohols compete with glycerol (hence also with the glycerophosphate product) for a hydroxy binding site on the enzyme. This leads to more rapid dissociation of the glycerophosphate (i.e. an increase in the steady-state constant, \"k+2\" resulting in an increased V)."}
{"id": "PMID:238628", "title": "Protamine kinase from yeast.", "content": "A protein kinase (ATP: protein phosphotransferase, EC 2.7.1.37) which preferentially phosphorylates protamine is purified about 250-fold from the soluble fraction of baker's yeast (Saccharomyces cerevisiae). This enzyme is not sensitive to activation by cyclic nucleotides. Histone is about 5% as active as protamine in the reaction rate. Neither casein, phosvitin nor glycogen phosphorylase is active as substrate. The enzyme is distinguishable from casein kinase of the classical type (Rabinowitz, M. and Lipmann, F. (1960) J. Biol. Chem. 235, 1043-1050) and from adenoshine 3', 5'-monophosphate-dependent protein kinase described earlier (Takai, Y., Yamamura, H. and Nishizuka, Y. (1974) J. Biol. Chem. 249,530-535).", "contents": "Protamine kinase from yeast. A protein kinase (ATP: protein phosphotransferase, EC 2.7.1.37) which preferentially phosphorylates protamine is purified about 250-fold from the soluble fraction of baker's yeast (Saccharomyces cerevisiae). This enzyme is not sensitive to activation by cyclic nucleotides. Histone is about 5% as active as protamine in the reaction rate. Neither casein, phosvitin nor glycogen phosphorylase is active as substrate. The enzyme is distinguishable from casein kinase of the classical type (Rabinowitz, M. and Lipmann, F. (1960) J. Biol. Chem. 235, 1043-1050) and from adenoshine 3', 5'-monophosphate-dependent protein kinase described earlier (Takai, Y., Yamamura, H. and Nishizuka, Y. (1974) J. Biol. Chem. 249,530-535)."}
{"id": "PMID:238629", "title": "3':5'-cyclic-nucleotide phosphodiesterases of mammalian sera.", "content": "Cyclic AMP and cyclic GMP phosphodiesterases (3':5'-cyclic-nucleotide 5'-nucleotidohydrolase EC 3.1.4.17) were found in the sera of human, dog, rabbit and rat. The formed elements of blood were not present in sera and thus not the source of the phosphodiesterase. More rapid hydrolysis of cyclic GMP than cyclic AMP is observed in the sera of these four species when 0.4 muM of cyclic AMP or cyclic GMP is used as the substrate. Protein activator of the phosphodiesterase is not detectable in the sera of these four species. Serum cyclic AMP and cyclic GMP phosphodiesterase activities are not stimulated by protein activator prepared from bovine brain. The serum phosphodiesterases of these four species are purified through Sepharose 6B column chromatography. Cyclic AMP phosphodiesterase are found in a broad area corresponding to molecular weights ranging from approximately 150 000 to 340 000 with 2 to 3 peaks in all animals tested. Cyclic GMP hosphodiesterase is found in a single area corresponding to molecular weights of 230 000 (rabbit and rat) and 270 000 (human and dog). Serum cyclic AMP and cyclic GMP hosphodiesterase activities of these four species have pH optimum of 7.5-8.5. Optimal concentration of Mg-2+ is about 5 mM for cyclic GMP phosphodiesterase activities of these four species as well as for cyclic AMP phosphodiesterase activities except rabbit. Rabbit serum cyclic AMP phosphodiesterase requires higher concentration of Mg-2+ (50 mM) for its optimal activity. The double reciprocal plots are non-linear for cyclic AMP phosphodiesterases of all animals and cyclic GMP phosphodiesterases of human, dog and rat. Rabbit cyclic GMP phosphodiesterase exhibits  a linear reciprocal plot. Cyclic GMP is inhibitor of serum cyclic AM phosphodiesterase. Rabbit enzyme was most effectively inhibited by cyclic GMP.", "contents": "3':5'-cyclic-nucleotide phosphodiesterases of mammalian sera. Cyclic AMP and cyclic GMP phosphodiesterases (3':5'-cyclic-nucleotide 5'-nucleotidohydrolase EC 3.1.4.17) were found in the sera of human, dog, rabbit and rat. The formed elements of blood were not present in sera and thus not the source of the phosphodiesterase. More rapid hydrolysis of cyclic GMP than cyclic AMP is observed in the sera of these four species when 0.4 muM of cyclic AMP or cyclic GMP is used as the substrate. Protein activator of the phosphodiesterase is not detectable in the sera of these four species. Serum cyclic AMP and cyclic GMP phosphodiesterase activities are not stimulated by protein activator prepared from bovine brain. The serum phosphodiesterases of these four species are purified through Sepharose 6B column chromatography. Cyclic AMP phosphodiesterase are found in a broad area corresponding to molecular weights ranging from approximately 150 000 to 340 000 with 2 to 3 peaks in all animals tested. Cyclic GMP hosphodiesterase is found in a single area corresponding to molecular weights of 230 000 (rabbit and rat) and 270 000 (human and dog). Serum cyclic AMP and cyclic GMP hosphodiesterase activities of these four species have pH optimum of 7.5-8.5. Optimal concentration of Mg-2+ is about 5 mM for cyclic GMP phosphodiesterase activities of these four species as well as for cyclic AMP phosphodiesterase activities except rabbit. Rabbit serum cyclic AMP phosphodiesterase requires higher concentration of Mg-2+ (50 mM) for its optimal activity. The double reciprocal plots are non-linear for cyclic AMP phosphodiesterases of all animals and cyclic GMP phosphodiesterases of human, dog and rat. Rabbit cyclic GMP phosphodiesterase exhibits  a linear reciprocal plot. Cyclic GMP is inhibitor of serum cyclic AM phosphodiesterase. Rabbit enzyme was most effectively inhibited by cyclic GMP."}
{"id": "PMID:238630", "title": "Characterisation of cyclic adenosine 3':5'-monophosphate phospodiesterase from Walker carcinoma sensitive and resistant to bifunctional alkylating agents.", "content": "Walker carcinoma cell lines sensitive or resistant to bifunctional alkylating agents have been found to contain multiple forms of cyclic AMP phosphodiesterase (3':5'-cyclic AMP 5'-nucleotidohydrolase, EC 3.1.4.17). These activities have been resolved using Sepharose 6B gel filtration and their apparent molecular weights have been estimated. The enzyme appears to occur in four active forms of apparent mol. wts of greater than 1 000 000, 430 000, 350 000 and 225 000, when assayed at low substrate concentrations. Evidence has been obtained which suggests that all four forms of the enzyme are composed of subunits of mol. wt of approximately 15 000 and are interconvertible. While the ionic strength of the buffer affected the predominance of the different forms, the presence of cyclic AMP at 10(-6) M had no effect on aggregation or dissociation of the enzyme. An activity shift from high molecular weight forms of the enzyme to low molecular weight forms has been found in the resistant tumour at low substrate concentration. No change in elution profile between sensitive and resistant tumours was observed for the low affinity form of the enzyme. The pH optima of the enzymes with both high and low affinity for the substrate was found to be pH 8.0 in the sensitive line. In the resistant tumour the pH optima of the high affinity form is shifted to pH 8.4 while the low affinity form remains at pH 8.0. The high affinity forms of the phosphodiesterase in the sensitive and resistant tumour also differed in their inhibition by theophylline. In both cases inhibition was of the competitive type with Ki values for the sensitive and resistant lines being 2.35 and 0.32 mM, respectively. There was no significant difference in the inhibition of the low affinity form between the sensitive and resistant tumour.", "contents": "Characterisation of cyclic adenosine 3':5'-monophosphate phospodiesterase from Walker carcinoma sensitive and resistant to bifunctional alkylating agents. Walker carcinoma cell lines sensitive or resistant to bifunctional alkylating agents have been found to contain multiple forms of cyclic AMP phosphodiesterase (3':5'-cyclic AMP 5'-nucleotidohydrolase, EC 3.1.4.17). These activities have been resolved using Sepharose 6B gel filtration and their apparent molecular weights have been estimated. The enzyme appears to occur in four active forms of apparent mol. wts of greater than 1 000 000, 430 000, 350 000 and 225 000, when assayed at low substrate concentrations. Evidence has been obtained which suggests that all four forms of the enzyme are composed of subunits of mol. wt of approximately 15 000 and are interconvertible. While the ionic strength of the buffer affected the predominance of the different forms, the presence of cyclic AMP at 10(-6) M had no effect on aggregation or dissociation of the enzyme. An activity shift from high molecular weight forms of the enzyme to low molecular weight forms has been found in the resistant tumour at low substrate concentration. No change in elution profile between sensitive and resistant tumours was observed for the low affinity form of the enzyme. The pH optima of the enzymes with both high and low affinity for the substrate was found to be pH 8.0 in the sensitive line. In the resistant tumour the pH optima of the high affinity form is shifted to pH 8.4 while the low affinity form remains at pH 8.0. The high affinity forms of the phosphodiesterase in the sensitive and resistant tumour also differed in their inhibition by theophylline. In both cases inhibition was of the competitive type with Ki values for the sensitive and resistant lines being 2.35 and 0.32 mM, respectively. There was no significant difference in the inhibition of the low affinity form between the sensitive and resistant tumour."}
{"id": "PMID:238631", "title": "Intracellular distribution of beta-galactosidases in mucosal cells from hog small intestine.", "content": "1. Intracellular distribution of three types of beta-galactosidases (beta-D-galactoside galactohydrolase EC 3.2.1.12) i.e. hetero beta-galactosidase, lactase and acid beta-galactosidase, was studied by examining the properties of subcellular fractions isolated by a systematic fractionation of mucosal cells of the small intestine of the hog. Localization of hetero beta-galactosidase in cytosol could be shown. 2. Localization of lactase in the brush borders was shown by analyzing the purified brush borders prepared separately. 3. To domonstrate the lysosomal localization of acid belta-galactosidase, lysosomes were purified separately and their extract was chromatographed on a hydroxylapatite column. The activities of various enzymes in the purified lysosomes as well as in the intermediary fractions obtained during lysosome purification and the pattern of the hydroxylapatite chromatography led us to conclude that acid beta-galactosidase is a lysosomal enzyme.", "contents": "Intracellular distribution of beta-galactosidases in mucosal cells from hog small intestine. 1. Intracellular distribution of three types of beta-galactosidases (beta-D-galactoside galactohydrolase EC 3.2.1.12) i.e. hetero beta-galactosidase, lactase and acid beta-galactosidase, was studied by examining the properties of subcellular fractions isolated by a systematic fractionation of mucosal cells of the small intestine of the hog. Localization of hetero beta-galactosidase in cytosol could be shown. 2. Localization of lactase in the brush borders was shown by analyzing the purified brush borders prepared separately. 3. To domonstrate the lysosomal localization of acid belta-galactosidase, lysosomes were purified separately and their extract was chromatographed on a hydroxylapatite column. The activities of various enzymes in the purified lysosomes as well as in the intermediary fractions obtained during lysosome purification and the pattern of the hydroxylapatite chromatography led us to conclude that acid beta-galactosidase is a lysosomal enzyme."}
{"id": "PMID:238632", "title": "Purification and some properties of alkaline pullulanase from a strain of bacillus no. 202-1, an alkalophilic microorganism.", "content": "Pullulanase (pullulan 6-glucanohydrolase EC 3.2.1.41) was purified about 290-fold from the culture fluid of Bacillus No. 202-1 by DEAE-cellulose adsorption, acetone fractionation, (NH4) 2SO4 precipitation and DEAE--cellulose column chromatography followed by Sephadex G-200 molecular sieve chromatography. The enzyme gave a single band of protein by disc polyacrylamide gel electrophoresis. The molecular weight was estimated as 92 000 by sodium dodecyl sulfate gel electrophoresis. The isolectric point was lower than pH 2.5. The optimum pH for enzyme action was about 8.5-9.0. The action of the enzyme on amylopectin and glycogen resulted in increase in the iodine coloration of 85% and 70%, respectively. The enzyme completely hydrolyzed 1,6-alpha-glucosidic linkages in amylopectin, glycogen and pullulan.", "contents": "Purification and some properties of alkaline pullulanase from a strain of bacillus no. 202-1, an alkalophilic microorganism. Pullulanase (pullulan 6-glucanohydrolase EC 3.2.1.41) was purified about 290-fold from the culture fluid of Bacillus No. 202-1 by DEAE-cellulose adsorption, acetone fractionation, (NH4) 2SO4 precipitation and DEAE--cellulose column chromatography followed by Sephadex G-200 molecular sieve chromatography. The enzyme gave a single band of protein by disc polyacrylamide gel electrophoresis. The molecular weight was estimated as 92 000 by sodium dodecyl sulfate gel electrophoresis. The isolectric point was lower than pH 2.5. The optimum pH for enzyme action was about 8.5-9.0. The action of the enzyme on amylopectin and glycogen resulted in increase in the iodine coloration of 85% and 70%, respectively. The enzyme completely hydrolyzed 1,6-alpha-glucosidic linkages in amylopectin, glycogen and pullulan."}
{"id": "PMID:238633", "title": "Interactions between K+ and ATP binding to the (Na+ + K+)-dependent ATPase.", "content": "K+ appears to decrease the affinity of the (Na+ + K+)-dependent ATPase (ATP phosphohydrolase, EC 3.6.1.3) for its substrate, Mg2+ - ATP, and Mg2+ - ATP, in turn, appears to decrease the affinity of the enzyme for K+. These antagonisms have been investigated in terms of a quantitative model defining the magnitude of the effects as well as identifying the class of K+ sites on the enzyme involved. K+ increased the apparent Km for Mg2+ - ATP, an effect that was antagonized competitively by Na+. The data can be fitted to a model in which Mg2+ - ATP binding is prevented by occupancy of alpha-sites on the enzyme by K+ (i.e. sites of moderate affinity for K+ accessible on the \"free\" non-phosphorylated enzyme, in situ on the external membrane surface). By contrast, occupancy of these alpha-sites by Na+ has no effect on Mg2+ - ATP binding to the enzyme. On the other hand, Mg2+ - ATP decreased the apparent affinity of the enzyme for K+ at the alpha-sites, in terms of (i) the KD for K+ measured by K+-accelerated inactivation of the enzyme by F-, and (ii) the concentration of K+ for half-maximal activation of the K+-dependent phosphatase reaction (which reflects the terminal hydrolytic steps of the overall ATPase reaction). These data fit the same quantitative model. Although this formulation does not support schemes in which ATP binding effects the release of transported K+ from discharge sites, it is consistent with observations that K+ can inhibit the enzyme at low substrate concentrations, and that Li+, which has poor efficacy when occupying these alpha-sites, can stimulate enzymatic activity at high K+ concentrations by displacing the inhibitory K+.", "contents": "Interactions between K+ and ATP binding to the (Na+ + K+)-dependent ATPase. K+ appears to decrease the affinity of the (Na+ + K+)-dependent ATPase (ATP phosphohydrolase, EC 3.6.1.3) for its substrate, Mg2+ - ATP, and Mg2+ - ATP, in turn, appears to decrease the affinity of the enzyme for K+. These antagonisms have been investigated in terms of a quantitative model defining the magnitude of the effects as well as identifying the class of K+ sites on the enzyme involved. K+ increased the apparent Km for Mg2+ - ATP, an effect that was antagonized competitively by Na+. The data can be fitted to a model in which Mg2+ - ATP binding is prevented by occupancy of alpha-sites on the enzyme by K+ (i.e. sites of moderate affinity for K+ accessible on the \"free\" non-phosphorylated enzyme, in situ on the external membrane surface). By contrast, occupancy of these alpha-sites by Na+ has no effect on Mg2+ - ATP binding to the enzyme. On the other hand, Mg2+ - ATP decreased the apparent affinity of the enzyme for K+ at the alpha-sites, in terms of (i) the KD for K+ measured by K+-accelerated inactivation of the enzyme by F-, and (ii) the concentration of K+ for half-maximal activation of the K+-dependent phosphatase reaction (which reflects the terminal hydrolytic steps of the overall ATPase reaction). These data fit the same quantitative model. Although this formulation does not support schemes in which ATP binding effects the release of transported K+ from discharge sites, it is consistent with observations that K+ can inhibit the enzyme at low substrate concentrations, and that Li+, which has poor efficacy when occupying these alpha-sites, can stimulate enzymatic activity at high K+ concentrations by displacing the inhibitory K+."}
{"id": "PMID:238635", "title": "Oxidation of dicyano-bis(1,10 phenanthroline) iron(II) by compounds I and II of cytochrome c peroxidase.", "content": "The apparent bimolecular rate constant for the oxidation of dicyano-bis(1,10 phenanthroline) iron(II) by compound II of cytochrome c peroxidase (ferrocytochrome c; hydrogen-peroxide oxidoreductase EC 1.11.1.5) has been measured over the pH range 2.5-11.0 at 0.1 M ionic strength, 25 degrees C, by the stopped-flow technique. An ionizable group in the enzyme, with a pKa of 4.5, strongly influences the electron transfer rate between the ferrous complex and the oxidized site in the enzyme. The electron transfer is fastest when the group is protonated, with a rate constant of 2.9 - 10-5 M--1 - s-1. The rate constantdecreases over three orders of magnitude when the proton dissociates. The apparent bimolecular rate constant for the oxidation of the ferrous complex by compound I of cytochrome c peroxidase was determined between pH 3.5 and 6. Under all conditions where this rate constant could be measured it was about three times larger than that for the oxidation by compound II.", "contents": "Oxidation of dicyano-bis(1,10 phenanthroline) iron(II) by compounds I and II of cytochrome c peroxidase. The apparent bimolecular rate constant for the oxidation of dicyano-bis(1,10 phenanthroline) iron(II) by compound II of cytochrome c peroxidase (ferrocytochrome c; hydrogen-peroxide oxidoreductase EC 1.11.1.5) has been measured over the pH range 2.5-11.0 at 0.1 M ionic strength, 25 degrees C, by the stopped-flow technique. An ionizable group in the enzyme, with a pKa of 4.5, strongly influences the electron transfer rate between the ferrous complex and the oxidized site in the enzyme. The electron transfer is fastest when the group is protonated, with a rate constant of 2.9 - 10-5 M--1 - s-1. The rate constantdecreases over three orders of magnitude when the proton dissociates. The apparent bimolecular rate constant for the oxidation of the ferrous complex by compound I of cytochrome c peroxidase was determined between pH 3.5 and 6. Under all conditions where this rate constant could be measured it was about three times larger than that for the oxidation by compound II."}
{"id": "PMID:238634", "title": "A calcium ion-dependent atp pyrophosphohydrolase in Physarum polycephalum.", "content": "An activity of ATP Pyrophosphohydrolase (EC 3.6.1.8) was found in the soluble fraction of the plasmodium of Physarum polycephalum. The products of the enzyme reaction were inorganic pyrophosphate and 5'-AMP in equimolar quantities. The enzyme had a pronounced requirement for Ca2+ with high specificity. Mg-2+ was not an essential cofactor but stimulated the enzyme activity about 2.5-fold of the control. The enzyme hydrolyzed ITP, GTP and beta,gamma-methylene ATP at a limited rate. Among inhibitors tested, 3 mM caffeine reduced the activity to about 75% of the control. The enzyme had a broad pH optimum around pH=7.0 and the Km for ATP was 2.0 mM. An Arrhenius plot showed a break at about 18 degrees C and the calculated activation energies were 6.7 and 11.4 kcal/mol above and below the transition temperature, respectively. Disc electrophoresis in dodecyl sulfate and gel filtration on Sephadex -g-200 gave apparent molecular weights of 56 000 and 240 000, respectively, suggesting that the native enzyme was built up from 4 polypeptide chains. The possible role of the enzyme in vivo was discussed.", "contents": "A calcium ion-dependent atp pyrophosphohydrolase in Physarum polycephalum. An activity of ATP Pyrophosphohydrolase (EC 3.6.1.8) was found in the soluble fraction of the plasmodium of Physarum polycephalum. The products of the enzyme reaction were inorganic pyrophosphate and 5'-AMP in equimolar quantities. The enzyme had a pronounced requirement for Ca2+ with high specificity. Mg-2+ was not an essential cofactor but stimulated the enzyme activity about 2.5-fold of the control. The enzyme hydrolyzed ITP, GTP and beta,gamma-methylene ATP at a limited rate. Among inhibitors tested, 3 mM caffeine reduced the activity to about 75% of the control. The enzyme had a broad pH optimum around pH=7.0 and the Km for ATP was 2.0 mM. An Arrhenius plot showed a break at about 18 degrees C and the calculated activation energies were 6.7 and 11.4 kcal/mol above and below the transition temperature, respectively. Disc electrophoresis in dodecyl sulfate and gel filtration on Sephadex -g-200 gave apparent molecular weights of 56 000 and 240 000, respectively, suggesting that the native enzyme was built up from 4 polypeptide chains. The possible role of the enzyme in vivo was discussed."}
{"id": "PMID:238636", "title": "Further studies on tryptophan hydroxylase from neoplastic murine mast cells.", "content": "Tryptophan hydroxylase (tryptophan, tetrahydropteridine: oxygen oxidoreductase (5-hydroxylating) EC 1.14.16.4) purified from the neoplastic murine mast cells by hydroxylapatite chromatography following ammonium sulfate fractionation showed maximum activity at pH 6.0 in the presence of 2-mercaptoethanol, 2-amino-4-hydroxy-6,7-dimethyl-5,6,7,8-tetra-hydropteridine and Fe2+, and pH 7.6 to 8.0 in the absence of addED Fe2+. The Km values were 38.5 muM and 22.2 muM for tryptophan, 298 muM and 204 muM for 2-amino-4-hydroxy-6,7-dimethyl-5,6,7,8-tetra-hydropteridine, and 6.45% for oxygen in either presence or absence of added Fe-2+, respectively. From kinetic data the reaction mechanism of tryptophan hydroxylation appears to be of the sequential, rather than the ping-pong, type. Tryptophan hydroxylase from mast cells was considerably inhibited by o-phenanthroline like phenylalanine hydroxylase as well as tyrosine hydroxylase from other sources, and its Ki was between 1.2 muM and 4.53 muM. It was found that the inhibition by o-phenanthroline was competitive with respect to both tryptophan and 2-amino-4-hydroxy-6,7-dimethyl-5,6,7,8-tetrahydropteridine, but not molecular oxygen under the assay conditions employed.", "contents": "Further studies on tryptophan hydroxylase from neoplastic murine mast cells. Tryptophan hydroxylase (tryptophan, tetrahydropteridine: oxygen oxidoreductase (5-hydroxylating) EC 1.14.16.4) purified from the neoplastic murine mast cells by hydroxylapatite chromatography following ammonium sulfate fractionation showed maximum activity at pH 6.0 in the presence of 2-mercaptoethanol, 2-amino-4-hydroxy-6,7-dimethyl-5,6,7,8-tetra-hydropteridine and Fe2+, and pH 7.6 to 8.0 in the absence of addED Fe2+. The Km values were 38.5 muM and 22.2 muM for tryptophan, 298 muM and 204 muM for 2-amino-4-hydroxy-6,7-dimethyl-5,6,7,8-tetra-hydropteridine, and 6.45% for oxygen in either presence or absence of added Fe-2+, respectively. From kinetic data the reaction mechanism of tryptophan hydroxylation appears to be of the sequential, rather than the ping-pong, type. Tryptophan hydroxylase from mast cells was considerably inhibited by o-phenanthroline like phenylalanine hydroxylase as well as tyrosine hydroxylase from other sources, and its Ki was between 1.2 muM and 4.53 muM. It was found that the inhibition by o-phenanthroline was competitive with respect to both tryptophan and 2-amino-4-hydroxy-6,7-dimethyl-5,6,7,8-tetrahydropteridine, but not molecular oxygen under the assay conditions employed."}
{"id": "PMID:238637", "title": "Purification and characterization of two activities of the intracellular dextransucrase from Leuconostoc mesenteroides NRRL B-1299.", "content": "Dextransucrase (sucrose: 1,6-alpha-D-glucan 6-alpha-glucosyltransferase EC 2.4.1.5) activity of Leuconostoc mesenteroides NRRL B-1299 cells has been purified by adsorption on hydroxyapatite, followed by chromatographies on DEAE-cellulose and DEAE-Sephadex. The enzyme activity was readily separated into two principal forms of the enzyme, I and II, by DEAE-cellulose chromatography. Both enzymes I and II were purified to an electrophoretically homogeneous state in which the relative enzyme activities reached 32-and 14-fold of the original specimen, respectively. Molecular weights were 69 000 for the enzyme I and 79 000 for the enzyme II as determined by electrophoresis in sodium dodecyl sulphate-polyacrylamide, and no subunit structure was observed. Enzyme I had an optimum pH at 6.3-6.5 and exhibited a maximal activity at 45 degrees C, while the optimum pH and temperature of enzyme II were pH 5.5-5.9 and 35-40 degrees C. The Km values of enzymes I and II were 10.7 and 250 mM, respectively. The effects of several metal ions, chemical reagents, and addition of various dextrans were also examined. Beside linear alpha-1,6-linkages the polymer synthesized by the enzyme II contained lesser amount of alpha-1,2-and alpha-1,3-linkages, which seems to be a primary characteristic of the B-1299 dextran.", "contents": "Purification and characterization of two activities of the intracellular dextransucrase from Leuconostoc mesenteroides NRRL B-1299. Dextransucrase (sucrose: 1,6-alpha-D-glucan 6-alpha-glucosyltransferase EC 2.4.1.5) activity of Leuconostoc mesenteroides NRRL B-1299 cells has been purified by adsorption on hydroxyapatite, followed by chromatographies on DEAE-cellulose and DEAE-Sephadex. The enzyme activity was readily separated into two principal forms of the enzyme, I and II, by DEAE-cellulose chromatography. Both enzymes I and II were purified to an electrophoretically homogeneous state in which the relative enzyme activities reached 32-and 14-fold of the original specimen, respectively. Molecular weights were 69 000 for the enzyme I and 79 000 for the enzyme II as determined by electrophoresis in sodium dodecyl sulphate-polyacrylamide, and no subunit structure was observed. Enzyme I had an optimum pH at 6.3-6.5 and exhibited a maximal activity at 45 degrees C, while the optimum pH and temperature of enzyme II were pH 5.5-5.9 and 35-40 degrees C. The Km values of enzymes I and II were 10.7 and 250 mM, respectively. The effects of several metal ions, chemical reagents, and addition of various dextrans were also examined. Beside linear alpha-1,6-linkages the polymer synthesized by the enzyme II contained lesser amount of alpha-1,2-and alpha-1,3-linkages, which seems to be a primary characteristic of the B-1299 dextran."}
{"id": "PMID:238638", "title": "Regulation of hepatic tyrosine aminotransferase in the frog Rana temporaria.", "content": "The regulation of hepatic tyrosine aminotransferase (L-tyrosine:2-oxoglutarate aminotransferase, EC 2.6.1.5) in the rat has been extensively studied but little is known about the enzyme from other sources. We have studied the regulation of this enzyme in the frog Rana temporaria and in this paper we report that: 1. Cortisone acetate, adrenocorticotropic hormone and alpha-methyl-p-tyrosine, an agent known to induce hepatic tyrosine aminotransferase in the rat via activation of the pituitary-adrenal axis, have no effect on the activity of the enzyme in the frog. 2. Dibutyryl-3',5'-cyclic AMP induces the enzyme to about 2-fold. 3. Injection of tyrosine methyl ester and a protein-rich diet result in an increase in the enzyme activity. This increase is of the same order of magnitude as that caused by dibutyryl cyclic AMP. 4. Glucose significantly reduces tyrosine aminotransferase activity in frog liver. These results suggest that cyclic AMP induces the enzyme via a mechanism independent of glucocorticoids. The frog offers a model for studies on the regulation of hepatic tyrosine aminotransferase in vivo without interference from secondary effects mediated by the adrenals.", "contents": "Regulation of hepatic tyrosine aminotransferase in the frog Rana temporaria. The regulation of hepatic tyrosine aminotransferase (L-tyrosine:2-oxoglutarate aminotransferase, EC 2.6.1.5) in the rat has been extensively studied but little is known about the enzyme from other sources. We have studied the regulation of this enzyme in the frog Rana temporaria and in this paper we report that: 1. Cortisone acetate, adrenocorticotropic hormone and alpha-methyl-p-tyrosine, an agent known to induce hepatic tyrosine aminotransferase in the rat via activation of the pituitary-adrenal axis, have no effect on the activity of the enzyme in the frog. 2. Dibutyryl-3',5'-cyclic AMP induces the enzyme to about 2-fold. 3. Injection of tyrosine methyl ester and a protein-rich diet result in an increase in the enzyme activity. This increase is of the same order of magnitude as that caused by dibutyryl cyclic AMP. 4. Glucose significantly reduces tyrosine aminotransferase activity in frog liver. These results suggest that cyclic AMP induces the enzyme via a mechanism independent of glucocorticoids. The frog offers a model for studies on the regulation of hepatic tyrosine aminotransferase in vivo without interference from secondary effects mediated by the adrenals."}
{"id": "PMID:238639", "title": "Enzymic reactions of fatty acid hydroperoxides in extracts of potato tuber. I. Comparison 9D- and 13L-hydroperoxy-octadecadienoic acids as substrates for the formation of a divinyl ether derivative.", "content": "1. 9-D-Hydroperoxy-octadeca-trans-10, cis-12-dienoic acid (formed from linoleic acid by potato lipoxygenase) is enzymically converted to a divinyl ether derivative (colneleic acid) by extracts of potato tuber. 2. the isomeric 13-L-hydroperoxide (formed from linoleic acid by soyabean lipoxygenase) is not a substrate for this enzyme system. 3. the enzyme reaction was not dependent on oxygen and was unaffected by metal chelators and thiol reagents. 4. studies with 18O-labelled substrate indicate that the ether oxygen atom in colneleic acid is not derived from the oxygens of the hydroperoxide group.", "contents": "Enzymic reactions of fatty acid hydroperoxides in extracts of potato tuber. I. Comparison 9D- and 13L-hydroperoxy-octadecadienoic acids as substrates for the formation of a divinyl ether derivative. 1. 9-D-Hydroperoxy-octadeca-trans-10, cis-12-dienoic acid (formed from linoleic acid by potato lipoxygenase) is enzymically converted to a divinyl ether derivative (colneleic acid) by extracts of potato tuber. 2. the isomeric 13-L-hydroperoxide (formed from linoleic acid by soyabean lipoxygenase) is not a substrate for this enzyme system. 3. the enzyme reaction was not dependent on oxygen and was unaffected by metal chelators and thiol reagents. 4. studies with 18O-labelled substrate indicate that the ether oxygen atom in colneleic acid is not derived from the oxygens of the hydroperoxide group."}
{"id": "PMID:238640", "title": "Preparation of 32P-labeled inositides and their degradation by soluble kidney enzymes.", "content": "A method is described for the preparation of radioactive inositol lipids for studies of their enzymic degradation. Kidney cytosol fractions have been used to produce diesteratic cleavage. High voltage electrophoresis at pH 4.3 is used to separate D-myoinositol 1 : 2-cyclic phosphate and D-myoinositol 1-phosphate from hydrolysis of phosphatidylinositol. Radioactivity co-migrating with myoinositol diphosphate and triphosphate is separated by electrophoresis at pH 1.5 following enzymatic hydrolysis of phosphatidylinositol phosphate and phosphatidylinositol diphosphate. Relative activities for hydrolysis of the various inositides suggest the presence of more than one phosphodiesterase.", "contents": "Preparation of 32P-labeled inositides and their degradation by soluble kidney enzymes. A method is described for the preparation of radioactive inositol lipids for studies of their enzymic degradation. Kidney cytosol fractions have been used to produce diesteratic cleavage. High voltage electrophoresis at pH 4.3 is used to separate D-myoinositol 1 : 2-cyclic phosphate and D-myoinositol 1-phosphate from hydrolysis of phosphatidylinositol. Radioactivity co-migrating with myoinositol diphosphate and triphosphate is separated by electrophoresis at pH 1.5 following enzymatic hydrolysis of phosphatidylinositol phosphate and phosphatidylinositol diphosphate. Relative activities for hydrolysis of the various inositides suggest the presence of more than one phosphodiesterase."}
{"id": "PMID:238641", "title": "Ceramidase and ceramide synthesis in human kidney and cerebellum. Description of a new alkaline ceramidase.", "content": "It has been shown that tissues of patients with Farber's disease characteristically lack acid (pH 4.0) ceramidase. In normal cerebellum, however, ceramide cleavage and the reverse reaction, free fatty acid-dependent ceramide synthesis, both occur not only at pH 4.0 but also at pH 9.0, although normal kidney exhibits these activities only at pH 4.0. Both tissues are capable of snythesizing ceramide via an acyl-COA-dependent pathway at neutral pH. The synthetic analog of ceramide, N-oleoyl-ethanolamine, is a potent inhibitor of ceramidase.", "contents": "Ceramidase and ceramide synthesis in human kidney and cerebellum. Description of a new alkaline ceramidase. It has been shown that tissues of patients with Farber's disease characteristically lack acid (pH 4.0) ceramidase. In normal cerebellum, however, ceramide cleavage and the reverse reaction, free fatty acid-dependent ceramide synthesis, both occur not only at pH 4.0 but also at pH 9.0, although normal kidney exhibits these activities only at pH 4.0. Both tissues are capable of snythesizing ceramide via an acyl-COA-dependent pathway at neutral pH. The synthetic analog of ceramide, N-oleoyl-ethanolamine, is a potent inhibitor of ceramidase."}
{"id": "PMID:238642", "title": "Subcellular fractionation, partial purification and characterization of neutral triacylglycerol lipase from pig liver.", "content": "The subcellular distributions of acidic (pH 4.5) and neutral (pH 7.5) longchain triacylglycerol lipases (glycerol ester hydrolase, EC 3.1.1.3) of pig liver have been determined. The distribution of the acidic lipase closely paralleled that of the lysosomal marker enzyme, cathepsin D. Approx. 60% of the neutral lipolytic activity resided in the soluble fraction;the distribution of this activity failed to parallel that of marker enzymes for mitochondria, lysosomes, microsomes, or plasma membranes. A method has been developed for purification of the neutral lipase from the soluble fraction by ultracentrifugation. An approximate 90-fold purification was achieved, with recovery of 16% of the initial activity. The partially purified neutral lipase exhibited a pH optimum between 7.25 and 7.5. It required 30 mM emulsified triolein for optimal activity and ceased to liberate fatty acids after 30 min of incubation. The enzymatic activity was destroyed by heating at 60 degrees C. Neutral lipase was inhibited by sodium deoxycholate, Triton X-100 and iodoacetamide. The activity was not inhibited by sodium taurocholate, EDTA, heparin and diethyl-p-nitrophenyl phosphate. Neutral lipase failed to exhibit activity in assay systems specific for lipoprotein lipase, monoolein hydrolase, tributyrinase, and methyl butyrate esterase and showed little or no capacity to hydrolyze chyle chylomicrons or plasma very low density lipoproteins. It is suggested that the function of neutral lipase may be to supply the liver with fatty acids liberated from endogenously synthesized or stored triacylglycerols.", "contents": "Subcellular fractionation, partial purification and characterization of neutral triacylglycerol lipase from pig liver. The subcellular distributions of acidic (pH 4.5) and neutral (pH 7.5) longchain triacylglycerol lipases (glycerol ester hydrolase, EC 3.1.1.3) of pig liver have been determined. The distribution of the acidic lipase closely paralleled that of the lysosomal marker enzyme, cathepsin D. Approx. 60% of the neutral lipolytic activity resided in the soluble fraction;the distribution of this activity failed to parallel that of marker enzymes for mitochondria, lysosomes, microsomes, or plasma membranes. A method has been developed for purification of the neutral lipase from the soluble fraction by ultracentrifugation. An approximate 90-fold purification was achieved, with recovery of 16% of the initial activity. The partially purified neutral lipase exhibited a pH optimum between 7.25 and 7.5. It required 30 mM emulsified triolein for optimal activity and ceased to liberate fatty acids after 30 min of incubation. The enzymatic activity was destroyed by heating at 60 degrees C. Neutral lipase was inhibited by sodium deoxycholate, Triton X-100 and iodoacetamide. The activity was not inhibited by sodium taurocholate, EDTA, heparin and diethyl-p-nitrophenyl phosphate. Neutral lipase failed to exhibit activity in assay systems specific for lipoprotein lipase, monoolein hydrolase, tributyrinase, and methyl butyrate esterase and showed little or no capacity to hydrolyze chyle chylomicrons or plasma very low density lipoproteins. It is suggested that the function of neutral lipase may be to supply the liver with fatty acids liberated from endogenously synthesized or stored triacylglycerols."}
{"id": "PMID:238643", "title": "Partial purification and properties of phospholipase A2 from the starfish, Asterina pectinifera.", "content": "1. Phospholipase A2 (phosphatide 2-acyl-hydrolase, EC 3.1.1.4) activity was shown to occur in the supernatant fraction of a freshly prepared homogenate from the pyloric caecum of starfish (Asterina pectinifera). 2. The phospholipase A2 has been isolated and purified 130-fold by ultracentrifugation, ammonium sulfate precipitation and column chromatographic procedures. 3. The purified enzyme was stable to heat at low pH values and the optimal pH was observed at approximately 9.0. 4. The enzyme activity was activated by Ca2+ and sodium deoxycholate, and was inhibited by EDTA.", "contents": "Partial purification and properties of phospholipase A2 from the starfish, Asterina pectinifera. 1. Phospholipase A2 (phosphatide 2-acyl-hydrolase, EC 3.1.1.4) activity was shown to occur in the supernatant fraction of a freshly prepared homogenate from the pyloric caecum of starfish (Asterina pectinifera). 2. The phospholipase A2 has been isolated and purified 130-fold by ultracentrifugation, ammonium sulfate precipitation and column chromatographic procedures. 3. The purified enzyme was stable to heat at low pH values and the optimal pH was observed at approximately 9.0. 4. The enzyme activity was activated by Ca2+ and sodium deoxycholate, and was inhibited by EDTA."}
{"id": "PMID:238644", "title": "Studies on the mechanism of the NADPH-catalyzed peroxidation of endogenous microsomal lipid.", "content": "The importance of metal chelation in the mechanism of microsomal lipid peroxidation has been studied using both phosphate- and sulfhydryl-containing compounds. The optimal concentration for maximum stimulation by each of these compounds has been determined, and the decrease in stimulation observe at concentrations above the maxima has been related to the ability of these compounds to form stable chelation complexes with non-heme iron. Of the compounds tested, only ADP and ATP facilitated the cooperative binding of NADPH to the membrane and thus suggested the possibility of three binding sites for NADPH. Neither of the other two phosphate-chelating agents (Pi or PPi) and neither of the two thiols (cysteine or dithiothreitol)facilitated cooperative binding of NADPH. These data suggested that the adenine ring of ADP or ATP is directly involved in the cooperativity of NADPH binding. They also emphasized that the binding of the chelation complex to the protein is an important parameter in the mechanism of the NADPH-catalyzed peroxidation of endogenous microsomal lipids. Furthermore, stimulation of the rat of lipid peroxidation by sulhydryl-containing compounds, by freezing thawing the microsomal protein, and by treatment of the protein with detergent may be due to a decrease in this cooperative binding effect. Since cysteine and deoxycholate as well as freezing and thawing alter membrane structure, the stimulation of lipid peroxidation seems to involve some alteration to the structure of the microsomal membrane prior to the onset of enzymatic lipid peroxidation.", "contents": "Studies on the mechanism of the NADPH-catalyzed peroxidation of endogenous microsomal lipid. The importance of metal chelation in the mechanism of microsomal lipid peroxidation has been studied using both phosphate- and sulfhydryl-containing compounds. The optimal concentration for maximum stimulation by each of these compounds has been determined, and the decrease in stimulation observe at concentrations above the maxima has been related to the ability of these compounds to form stable chelation complexes with non-heme iron. Of the compounds tested, only ADP and ATP facilitated the cooperative binding of NADPH to the membrane and thus suggested the possibility of three binding sites for NADPH. Neither of the other two phosphate-chelating agents (Pi or PPi) and neither of the two thiols (cysteine or dithiothreitol)facilitated cooperative binding of NADPH. These data suggested that the adenine ring of ADP or ATP is directly involved in the cooperativity of NADPH binding. They also emphasized that the binding of the chelation complex to the protein is an important parameter in the mechanism of the NADPH-catalyzed peroxidation of endogenous microsomal lipids. Furthermore, stimulation of the rat of lipid peroxidation by sulhydryl-containing compounds, by freezing thawing the microsomal protein, and by treatment of the protein with detergent may be due to a decrease in this cooperative binding effect. Since cysteine and deoxycholate as well as freezing and thawing alter membrane structure, the stimulation of lipid peroxidation seems to involve some alteration to the structure of the microsomal membrane prior to the onset of enzymatic lipid peroxidation."}
{"id": "PMID:238645", "title": "The substrate for cholesterol 7alpha-hydroxylase.", "content": "The rates of incorporation of (14C) cholesterol into cholesteryl esters and 5-cholestene-3beta,7alpha-diol (7alpha-hydroxycholesterol) by rat liver microsomes, measured under conditions in which esterification and 7alpha-hydroxylation are varied independently, indicated that cholesterol is the substrate for cholesterol 7alpha-hydroxylase. The specific activities of cholesteryl esters and 7alpha-hydroxycholeste  ol in incubations of microsomes labelled with (14C)cholesterol in vitro or in vivo suggest that 7alpha-hydroxycholesterol and esterified cholesterol are not derived from the same pool of free cholesterol.", "contents": "The substrate for cholesterol 7alpha-hydroxylase. The rates of incorporation of (14C) cholesterol into cholesteryl esters and 5-cholestene-3beta,7alpha-diol (7alpha-hydroxycholesterol) by rat liver microsomes, measured under conditions in which esterification and 7alpha-hydroxylation are varied independently, indicated that cholesterol is the substrate for cholesterol 7alpha-hydroxylase. The specific activities of cholesteryl esters and 7alpha-hydroxycholeste  ol in incubations of microsomes labelled with (14C)cholesterol in vitro or in vivo suggest that 7alpha-hydroxycholesterol and esterified cholesterol are not derived from the same pool of free cholesterol."}
{"id": "PMID:238646", "title": "Some characteristics of the prostaglandin synthesizing system in rabbit kidney microsomes.", "content": "The prostaglandin synthesizing system in rabbit kidney microsomes was characterised using a radiometric assay. Three prostaglandins (F2alpha, E2 and D2) were formed form (1-14C)arachidonic acid, a small amount of prostaglandin A2 was also detected but this was formed non-enzymatically. Biosynthesis was stimulated by reduced-glutathione and 1-adrenaline and was inhibited by aspirin-like drugs. The enzyme system was sensitive to small changes in pH. There were substantial differences in drug sensitivity and optimal reaction conditions between this prostaglandin synthesizing system and the one from bovine seminal vesicles.", "contents": "Some characteristics of the prostaglandin synthesizing system in rabbit kidney microsomes. The prostaglandin synthesizing system in rabbit kidney microsomes was characterised using a radiometric assay. Three prostaglandins (F2alpha, E2 and D2) were formed form (1-14C)arachidonic acid, a small amount of prostaglandin A2 was also detected but this was formed non-enzymatically. Biosynthesis was stimulated by reduced-glutathione and 1-adrenaline and was inhibited by aspirin-like drugs. The enzyme system was sensitive to small changes in pH. There were substantial differences in drug sensitivity and optimal reaction conditions between this prostaglandin synthesizing system and the one from bovine seminal vesicles."}
{"id": "PMID:238647", "title": "Glutathione biosynthesis in Escherichia coli K 12. Properties of the enzymes and regulation.", "content": "The synthesis of glutathione in Escherichia coli K 12 was studied in crude, cell-free extracts. The pH optima and the apparent Km values for the substrates have been determined for both synthesizing enzymes, gamma-glutamylcysteine synthetase and glutathione synthetase. gamma-Glutamylcysteine synthetase was found to be approximately twice as active as glutathione synthetase. In a growing culture, the cellular level of GSH showed a considerable increase up to 6.6 mumol per ml cell pellet in the stationary growth phase. GSSG was not detectable. The levels of the enzymes remained constant, indicating that glutathione biosynthesis depends at least in the beginning on the availability of the component amino acids. The pathway is controlled by feedback inhibition and not by repression.", "contents": "Glutathione biosynthesis in Escherichia coli K 12. Properties of the enzymes and regulation. The synthesis of glutathione in Escherichia coli K 12 was studied in crude, cell-free extracts. The pH optima and the apparent Km values for the substrates have been determined for both synthesizing enzymes, gamma-glutamylcysteine synthetase and glutathione synthetase. gamma-Glutamylcysteine synthetase was found to be approximately twice as active as glutathione synthetase. In a growing culture, the cellular level of GSH showed a considerable increase up to 6.6 mumol per ml cell pellet in the stationary growth phase. GSSG was not detectable. The levels of the enzymes remained constant, indicating that glutathione biosynthesis depends at least in the beginning on the availability of the component amino acids. The pathway is controlled by feedback inhibition and not by repression."}
{"id": "PMID:238648", "title": "The characterisation and function of the polysaccharidases of human synovial fluid in rheumatoid and osteoarthritis.", "content": "A potential enzymic mechanism for the degradation of glycosaminogly cans was characterised using enzymes found in rheumatoid synovial fluid from the knee joint. This mechanism involves a true hyluronidase together with the concerted action of beta-glucuronidase and beta-N-acetylhexosaminidase. The contribution of the exopolysaccharidases to hyaluronate degradation was demonstrated by the use of specific inhibitors, while the distinct identity of a true hyaluronidase was shown by ammonium sulphate and agarose gel column fractionations. Only the hyluronidase fraction was capable of degrading high molecular weight hyaluronate. The exopolysaccharidase activities were shown to be markedly elevated in rheumatoid as compared to osteoarthritic synovial fluid and also normal serum. On the other hand, hyluronidase was similarly active in rheumatoid and osteoarthritic synovial fluids; both these levels were lower than that of normal human serum. Hyaluronidase in synovial fluid may thus be derived by diffusion from serum, since it is of relatively low molecular weight (60 000). The pH requirements of this enzyme system and the strong inhibition of hyaluronidase by synovial fluid make it unlikely that the mechanism operates extracellularly. It is proposed that as a lysosomal mechanism, however, it is an important contributing factor in the chronic erosion process characteristic of rheumatoid arthritis.", "contents": "The characterisation and function of the polysaccharidases of human synovial fluid in rheumatoid and osteoarthritis. A potential enzymic mechanism for the degradation of glycosaminogly cans was characterised using enzymes found in rheumatoid synovial fluid from the knee joint. This mechanism involves a true hyluronidase together with the concerted action of beta-glucuronidase and beta-N-acetylhexosaminidase. The contribution of the exopolysaccharidases to hyaluronate degradation was demonstrated by the use of specific inhibitors, while the distinct identity of a true hyaluronidase was shown by ammonium sulphate and agarose gel column fractionations. Only the hyluronidase fraction was capable of degrading high molecular weight hyaluronate. The exopolysaccharidase activities were shown to be markedly elevated in rheumatoid as compared to osteoarthritic synovial fluid and also normal serum. On the other hand, hyluronidase was similarly active in rheumatoid and osteoarthritic synovial fluids; both these levels were lower than that of normal human serum. Hyaluronidase in synovial fluid may thus be derived by diffusion from serum, since it is of relatively low molecular weight (60 000). The pH requirements of this enzyme system and the strong inhibition of hyaluronidase by synovial fluid make it unlikely that the mechanism operates extracellularly. It is proposed that as a lysosomal mechanism, however, it is an important contributing factor in the chronic erosion process characteristic of rheumatoid arthritis."}
{"id": "PMID:238649", "title": "Human umbilical cord hyaluronate. Neutral sugar content and carbohydrate-protein linkage studies.", "content": "Paper chromatography of neutral sugars and gas chromatography of their aldononitrile acetates indicated the presence of fucose, arabinose and a small amount of glucose in purified human umbilical cord hyaluronate. The molar ratios of serine, threonine and aspartic acid to neutral sugars were not unity, suggesting the non-involvement of the neutral sugars and the amino acids in a carbohydrate-protein linkage. The same was indicated by an increase in the percentage of the aforementioned amino acids and by the absence of sugar alditols in umbilical cord hyaluronate reduced eith NaBH4 -PdCl2, after alkali treatment. This reduction caused a decrease in the intrinsic viscosity and molecular wieght to about one-half and an appreciable decrease in the specific rota tion of hyaluronate, suggesting a separation of the two antiparallel chains o the double helical hyaluronate. The umbilical cord hyluronate containe contained bound silicon and it is possible that this bound silicon may cross-link the two chains at interspersed intervals through the uronic acid moiety and/or through neutral sugars.", "contents": "Human umbilical cord hyaluronate. Neutral sugar content and carbohydrate-protein linkage studies. Paper chromatography of neutral sugars and gas chromatography of their aldononitrile acetates indicated the presence of fucose, arabinose and a small amount of glucose in purified human umbilical cord hyaluronate. The molar ratios of serine, threonine and aspartic acid to neutral sugars were not unity, suggesting the non-involvement of the neutral sugars and the amino acids in a carbohydrate-protein linkage. The same was indicated by an increase in the percentage of the aforementioned amino acids and by the absence of sugar alditols in umbilical cord hyaluronate reduced eith NaBH4 -PdCl2, after alkali treatment. This reduction caused a decrease in the intrinsic viscosity and molecular wieght to about one-half and an appreciable decrease in the specific rota tion of hyaluronate, suggesting a separation of the two antiparallel chains o the double helical hyaluronate. The umbilical cord hyluronate containe contained bound silicon and it is possible that this bound silicon may cross-link the two chains at interspersed intervals through the uronic acid moiety and/or through neutral sugars."}
{"id": "PMID:238650", "title": "Characterization of a colchicine receptor protein in rat epididymal adipose tissue.", "content": "Colchincine was found to be taken up by adipose tissue and therein to bind to a soluble macromolecule not sedimented by centrifugation for 2 h at 100 000 x g. A similar binding occurred when soluble extracts of adipose tissue were incubated with colchicine. The binding reaction reaction is temperature dependent and shows a pH optimum between 6.8 and 7.0. Double reciprocal plots of colchicine concentration versus amounts of colchicine bound to protein in the steady state disclosed an apparent Km of 0.250 to 1.5 muM. The colchicine binding activity of soluble tissue extracts decreased when the extracts were incubated at 37 degree C. Addition of guanosine triphosphate and Mg-2+ retarded the loss of colchicine binding activity. The molecular weight of the colchicine complex was estimated to be 115 000 and its sedimentation coefficient 5.8 S. All of these characteristics are remarkably similar to those of the protein tubulin which has been isolated from other tissues. Since it is now well known that tubulin is a protein subunit of cytoplasmic microtubules, it is suggested that the previously reported metabolic effects of colchicine on adipose tissue result from the dissolution of microtubules by colchicine.", "contents": "Characterization of a colchicine receptor protein in rat epididymal adipose tissue. Colchincine was found to be taken up by adipose tissue and therein to bind to a soluble macromolecule not sedimented by centrifugation for 2 h at 100 000 x g. A similar binding occurred when soluble extracts of adipose tissue were incubated with colchicine. The binding reaction reaction is temperature dependent and shows a pH optimum between 6.8 and 7.0. Double reciprocal plots of colchicine concentration versus amounts of colchicine bound to protein in the steady state disclosed an apparent Km of 0.250 to 1.5 muM. The colchicine binding activity of soluble tissue extracts decreased when the extracts were incubated at 37 degree C. Addition of guanosine triphosphate and Mg-2+ retarded the loss of colchicine binding activity. The molecular weight of the colchicine complex was estimated to be 115 000 and its sedimentation coefficient 5.8 S. All of these characteristics are remarkably similar to those of the protein tubulin which has been isolated from other tissues. Since it is now well known that tubulin is a protein subunit of cytoplasmic microtubules, it is suggested that the previously reported metabolic effects of colchicine on adipose tissue result from the dissolution of microtubules by colchicine."}
{"id": "PMID:238651", "title": "Interaction of nerve growth factor with tubulin. Studies on binding and induced polymerization.", "content": "The interaction of the nerve growth factor with the neurotubule protein has been studied with the aim of elucidating the nature of the large complexes that they form when incubated together and the factors and control this event. The results show that the binding of nerve growth factor to tubulin is followed by the formation of large structures that, in certain experimental conditions, accelerate the rate of tubulin polymerization to form microtubules or catalyze their assembly in conditions where this process does not occur spontaneously. The formation of large nerve growth factor-tubulin complexes starts to occur only at a molar ratio of 1.0-1.5 NaCL or GTP strongly inhibit this proceed without a detectable effect on NGF binding. Two hypotheses are postulated explain these findings. Firstly, that tubulin has two sites with different affinity for nerve growth factor and the polymerization occurs only when the second NGF molecule has interacted with the microtubule protein. Alternatively, free tubulin in solution is the polymerization by hindering site of tubulin-factor complexes present in solution at a 1.1 molar ratio. In both cases, GTP, Na-+ or H-+ will affect the formation of large unsoluble, tubulin-NGF complexes, by changing their conformation or by decreasing electrostatic interactions.", "contents": "Interaction of nerve growth factor with tubulin. Studies on binding and induced polymerization. The interaction of the nerve growth factor with the neurotubule protein has been studied with the aim of elucidating the nature of the large complexes that they form when incubated together and the factors and control this event. The results show that the binding of nerve growth factor to tubulin is followed by the formation of large structures that, in certain experimental conditions, accelerate the rate of tubulin polymerization to form microtubules or catalyze their assembly in conditions where this process does not occur spontaneously. The formation of large nerve growth factor-tubulin complexes starts to occur only at a molar ratio of 1.0-1.5 NaCL or GTP strongly inhibit this proceed without a detectable effect on NGF binding. Two hypotheses are postulated explain these findings. Firstly, that tubulin has two sites with different affinity for nerve growth factor and the polymerization occurs only when the second NGF molecule has interacted with the microtubule protein. Alternatively, free tubulin in solution is the polymerization by hindering site of tubulin-factor complexes present in solution at a 1.1 molar ratio. In both cases, GTP, Na-+ or H-+ will affect the formation of large unsoluble, tubulin-NGF complexes, by changing their conformation or by decreasing electrostatic interactions."}
{"id": "PMID:238652", "title": "Investigation of some physico-chemical properties of muscular parvalbumins by means of the luminescence of their phenylalanyl residues.", "content": "The influence of pH, temperature and Ca2+-release on the phenylalanyl and tyrosyl fluorescene of muscular parvalbumins from white muscles of hake and carp has been investigated. Within the pH range from 7 to 8, Ca2+-saturated parvalbumins show a conformational change registered by fluorescence, that is associated with the release of some of the bound Ca2+. Removal of Ca2+ by means of EGTA (ethyleneglycolbis-(aminoethylether)tetra-acetic acid) considerably narrows the region of protein nativity, increases the accessibility of their chromophores to quencher ions (Cs+ and CNS-) and decreases their stability against heat denaturation. The usefulness of measurements of the phenylalanine fluorescence and of the tyrosine-phenylalanine energy transfer in the investigation of these and other proteins is discussed.", "contents": "Investigation of some physico-chemical properties of muscular parvalbumins by means of the luminescence of their phenylalanyl residues. The influence of pH, temperature and Ca2+-release on the phenylalanyl and tyrosyl fluorescene of muscular parvalbumins from white muscles of hake and carp has been investigated. Within the pH range from 7 to 8, Ca2+-saturated parvalbumins show a conformational change registered by fluorescence, that is associated with the release of some of the bound Ca2+. Removal of Ca2+ by means of EGTA (ethyleneglycolbis-(aminoethylether)tetra-acetic acid) considerably narrows the region of protein nativity, increases the accessibility of their chromophores to quencher ions (Cs+ and CNS-) and decreases their stability against heat denaturation. The usefulness of measurements of the phenylalanine fluorescence and of the tyrosine-phenylalanine energy transfer in the investigation of these and other proteins is discussed."}
{"id": "PMID:238653", "title": "NMR studies of hemoproteins. VI. Acid-base transitions of ferric myoglobin and its imidazole complex.", "content": "220 MHz proton NMR was applied to the acid-base transition of ferric myoglobin and its imidazole complex. In horse and sperm whale ferric myoglobins: (1) pH-dependent shift of heme-ring methyl signals above p2H 10 was analyzed on the basis of rapid exchange between alkaline and acidic forms by the use of pK value 9.1 of acid-base transition in 1H20 solution; (2) limiting shifts of three methyl signals were reasonably determined for purely alkaline form. For the imidazole complex: (3) a drastic high field shift of each signal was observed above p2H 9.0, whereas N0methyl imidazole complex did not exhibit such a shift, which suggests the 2H+ dissociation from liganded imidazole greater than N2H. It is concluded thns.", "contents": "NMR studies of hemoproteins. VI. Acid-base transitions of ferric myoglobin and its imidazole complex. 220 MHz proton NMR was applied to the acid-base transition of ferric myoglobin and its imidazole complex. In horse and sperm whale ferric myoglobins: (1) pH-dependent shift of heme-ring methyl signals above p2H 10 was analyzed on the basis of rapid exchange between alkaline and acidic forms by the use of pK value 9.1 of acid-base transition in 1H20 solution; (2) limiting shifts of three methyl signals were reasonably determined for purely alkaline form. For the imidazole complex: (3) a drastic high field shift of each signal was observed above p2H 9.0, whereas N0methyl imidazole complex did not exhibit such a shift, which suggests the 2H+ dissociation from liganded imidazole greater than N2H. It is concluded thns."}
{"id": "PMID:238654", "title": "Studies of an acidic cardiotoxin isolated from the venom of Mojave rattlesnake (Crotalus scutulatus).", "content": "A major lethal protein was isolated from the venom of Mojave rattlesnake (Crotalus scutulatus) by successive purification in DEAE column chromatography and isoelectric focusing. This homogeneous and monomeric form of toxin is designated as \"Mojave toxin\". Unlike basic neurotoxins or cytotoxins isolated from venoms of cobras, kraits and sea snakes, the Mojave toxin is an acidic protein with an isoelectric point of 4.7. The toxin is also different from crotoxin (from Crotalus durissus terrificus) which consists of both acidic and basic components. The molecular weight determined by Sephadex G-75 column chromatography resulted in a value of about 22 000. A singel protein band with a molecular weight of about 12 000, was observed after sodium dodecyl sulfate gel electrophoresis of the reduced Mojave toxin. Isoelectric focusing gel in the presence of 8 M urea also showed a single protein band, suggesting that the toxin is composed of subunits. Unlike the neurotoxic nature of the basic proteins from the venoms of Elapidae and sea snakes (Hydrophiidae) and crotoxin, Mojave toxin is cardiotoxic rather than neurotoxic. It is very likely that venoms of all rattlesnakes from North and Central America contain Mojave toxin as the common toxin.", "contents": "Studies of an acidic cardiotoxin isolated from the venom of Mojave rattlesnake (Crotalus scutulatus). A major lethal protein was isolated from the venom of Mojave rattlesnake (Crotalus scutulatus) by successive purification in DEAE column chromatography and isoelectric focusing. This homogeneous and monomeric form of toxin is designated as \"Mojave toxin\". Unlike basic neurotoxins or cytotoxins isolated from venoms of cobras, kraits and sea snakes, the Mojave toxin is an acidic protein with an isoelectric point of 4.7. The toxin is also different from crotoxin (from Crotalus durissus terrificus) which consists of both acidic and basic components. The molecular weight determined by Sephadex G-75 column chromatography resulted in a value of about 22 000. A singel protein band with a molecular weight of about 12 000, was observed after sodium dodecyl sulfate gel electrophoresis of the reduced Mojave toxin. Isoelectric focusing gel in the presence of 8 M urea also showed a single protein band, suggesting that the toxin is composed of subunits. Unlike the neurotoxic nature of the basic proteins from the venoms of Elapidae and sea snakes (Hydrophiidae) and crotoxin, Mojave toxin is cardiotoxic rather than neurotoxic. It is very likely that venoms of all rattlesnakes from North and Central America contain Mojave toxin as the common toxin."}
{"id": "PMID:238655", "title": "Isoelectric focusing of proteins using a pH gradient created by a concentration gradient of nonelectrolytes in solution.", "content": "A new method of producing a stable pH gradient in buffer solutions is suggested, obtained by the concentration gradient of a nonelectrolyte in buffer solutions as a result of the gradual change in the dielectric properties of the solution. The maximal concentrations of nonelectrolyte which do not influence the protein configuration allow a pH gradient with a range of two pH units to be produced. It is suggested that the properties of some polyols (i.e. glycerol or mannitol) be used to change the pH of the borate buffer for the production of greater pH gradient with a range of up to 4-5 pH units. Creating the gradient of concentration of polyols, one can obtain a pH gradient in borate buffer solutions. Though the polylydroxyl compound-borate complexes posses mobility in an electric field, a stable pH gradient can be achieved during 12 days of electrophoresis. The isoelectric focusing of haemoglobin, human serum albumin and immunoglobulins was carried out in both systems suggested. These findings were compared with isoelectric focusing in Ampholines. There was a good agreement between the methods compared. The possible differences are discussed.", "contents": "Isoelectric focusing of proteins using a pH gradient created by a concentration gradient of nonelectrolytes in solution. A new method of producing a stable pH gradient in buffer solutions is suggested, obtained by the concentration gradient of a nonelectrolyte in buffer solutions as a result of the gradual change in the dielectric properties of the solution. The maximal concentrations of nonelectrolyte which do not influence the protein configuration allow a pH gradient with a range of two pH units to be produced. It is suggested that the properties of some polyols (i.e. glycerol or mannitol) be used to change the pH of the borate buffer for the production of greater pH gradient with a range of up to 4-5 pH units. Creating the gradient of concentration of polyols, one can obtain a pH gradient in borate buffer solutions. Though the polylydroxyl compound-borate complexes posses mobility in an electric field, a stable pH gradient can be achieved during 12 days of electrophoresis. The isoelectric focusing of haemoglobin, human serum albumin and immunoglobulins was carried out in both systems suggested. These findings were compared with isoelectric focusing in Ampholines. There was a good agreement between the methods compared. The possible differences are discussed."}
{"id": "PMID:238656", "title": "Interaction of troponin components with F-actin and F-actin-tropomyosin complex.", "content": "1. Both TN-T and TN-I components of troponin interact with F-actin, causing its precipitation at 0.1 M KC1 and neutral pH in a form of highly ordered paracrystals, although the ability of TN-I component to precipitate of F-actin is much weaker. 2. F-actin paracrystals obtained in the presence of both TN-T and TN-I components consist of parallel arrays of F-actin filaments, although the fine structure is in each case different. 3. In the presence of tropomyosin in the proportion equal to that in muscle, less TN-T or TN-I component is needed to obtain full precipitation of F-actin. 4. Paracrystals of F-actin-tropomyosin-TN-T component and F-actin-tropomyosin-TN-I component show regular transverse striation spaced at about 380 A intervals. 5. The TN-C component of troponin solubilizes all precipitates of F-actin with TN-T or TN-I components, regardless of the presence of tropomyosin. 6. The results show that both TN-T or TN-I components can bind independently to F-actin-tropomyosin complex with the same periodicity, similar to that of the whole troponin in the living muscle.", "contents": "Interaction of troponin components with F-actin and F-actin-tropomyosin complex. 1. Both TN-T and TN-I components of troponin interact with F-actin, causing its precipitation at 0.1 M KC1 and neutral pH in a form of highly ordered paracrystals, although the ability of TN-I component to precipitate of F-actin is much weaker. 2. F-actin paracrystals obtained in the presence of both TN-T and TN-I components consist of parallel arrays of F-actin filaments, although the fine structure is in each case different. 3. In the presence of tropomyosin in the proportion equal to that in muscle, less TN-T or TN-I component is needed to obtain full precipitation of F-actin. 4. Paracrystals of F-actin-tropomyosin-TN-T component and F-actin-tropomyosin-TN-I component show regular transverse striation spaced at about 380 A intervals. 5. The TN-C component of troponin solubilizes all precipitates of F-actin with TN-T or TN-I components, regardless of the presence of tropomyosin. 6. The results show that both TN-T or TN-I components can bind independently to F-actin-tropomyosin complex with the same periodicity, similar to that of the whole troponin in the living muscle."}
{"id": "PMID:238657", "title": "Interpretation of the electron spin resonance spectra of nitroxide-maleimide-labelled proteins and the use of this technique in the study of albumin and biomembranes.", "content": "The composite ESR spectra of nitroxide-maleimide spin-labelled albumin and mitochondrial membranes were investigated. It was found that the mobile spectrum (so called \"weakly immobilized\") is due to the probe free in solution; it could be removed by dialysis, by lowering the ratio of spin label to albumin or by using acid pH values. Similar degrees of mobility were noted with spectra of spin label in solutions with viscosities similar to that of albumin. The immobile spectrum (so called \"strongly immobilized\") is due to the binding of N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyl)-maleimide to the proteins. Studies with modified albumins have shown that in this binding the free SH and amino groups are involved, but the three-dimensional structure offering conditions for hydrophobic binding is also required. The spectral parameters useful for evaluating conformational changes of proteins and an application to mitochondrial membranes are described.", "contents": "Interpretation of the electron spin resonance spectra of nitroxide-maleimide-labelled proteins and the use of this technique in the study of albumin and biomembranes. The composite ESR spectra of nitroxide-maleimide spin-labelled albumin and mitochondrial membranes were investigated. It was found that the mobile spectrum (so called \"weakly immobilized\") is due to the probe free in solution; it could be removed by dialysis, by lowering the ratio of spin label to albumin or by using acid pH values. Similar degrees of mobility were noted with spectra of spin label in solutions with viscosities similar to that of albumin. The immobile spectrum (so called \"strongly immobilized\") is due to the binding of N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyl)-maleimide to the proteins. Studies with modified albumins have shown that in this binding the free SH and amino groups are involved, but the three-dimensional structure offering conditions for hydrophobic binding is also required. The spectral parameters useful for evaluating conformational changes of proteins and an application to mitochondrial membranes are described."}
{"id": "PMID:238658", "title": "A polypeptide conjugate of bilirubin from human bile.", "content": "An alkali-stable bilirubin conjugate has been obtained from human T-tube bile as its phenylazo derivative. The conjugate consists of a polypeptide probably of molecular weight 7000 to which the azo pigment of bilirubin is linked covalently through its carboxyl group. It thus constitutes the first biliprotein found in mammals. It is not known whether both carboxyl groups of native bilirubin participate in the binding of the conjugating protein, nor has it been possible to determine the number of pigment moieties occurring on a single polypeptide chain. The isolation makes use of the tendency of the conjugate to form large aggregates and involves the following steps: azo coupling of the native bile, (NH4)2S04 precipitation of macromolecules and aggregates, removal of low molecular weight contaminants by dialysis and gel filtration (first on Sepharose 6B IN 6 M guanidine, then on Sephadex LH-20 in 50% acqueous 2-chloroethanol) and a concluding purification by chromatography on p-aminobenzyl cellulose using a PH gradient. The final preparation appeared to be homogeneous on polyacrylamide electrophoresis.", "contents": "A polypeptide conjugate of bilirubin from human bile. An alkali-stable bilirubin conjugate has been obtained from human T-tube bile as its phenylazo derivative. The conjugate consists of a polypeptide probably of molecular weight 7000 to which the azo pigment of bilirubin is linked covalently through its carboxyl group. It thus constitutes the first biliprotein found in mammals. It is not known whether both carboxyl groups of native bilirubin participate in the binding of the conjugating protein, nor has it been possible to determine the number of pigment moieties occurring on a single polypeptide chain. The isolation makes use of the tendency of the conjugate to form large aggregates and involves the following steps: azo coupling of the native bile, (NH4)2S04 precipitation of macromolecules and aggregates, removal of low molecular weight contaminants by dialysis and gel filtration (first on Sepharose 6B IN 6 M guanidine, then on Sephadex LH-20 in 50% acqueous 2-chloroethanol) and a concluding purification by chromatography on p-aminobenzyl cellulose using a PH gradient. The final preparation appeared to be homogeneous on polyacrylamide electrophoresis."}
{"id": "PMID:238659", "title": "Properties of (Na+ plus K+)-activated ATPase in rat liver plasma membranes enriched with bile canaliculi.", "content": "Liver plasma membranes enriched in bile canaliculi were isolated from rat liver by a modification of the technique of Song et al. (J. Cell Biol. (1969) 41, 124-132) in order to study the possible role of ATPase in bile secretion. Optimum conditions for assaying (Na+ plus K+)-activated ATPase in this membrane fraction were defined using male rats averaging 220 g in weight. (Na+ plus K+)-activated ATPase activity was documented by demonstrating specific cation requirements for Na+ and K+, while the divalent cation, Ca(2+), and the cardiac glycosides, ouabain and scillaren, were inhibitory. (Na+ plus K+)-activated ATPase activity averaged 10.07 plus or minus 2.80 mumol Pi/mg protein per h compared to 50.03 plus or minus 11.41 for Mg(2+)-activated ATPase and 58.66 plus or minus 10.07 for 5'-nucleotidase. Concentrations of ouabain and scillaren which previously inhibited canalicular bile secretion in the isolated perfused rat liver produced complete inhibition of (Na+ plus K+)-activated ATPase without any effect on Mg(2+)-activated ATPase. Both (Na+ plus K+)-activated ATPase and Mg(2+)-activated ATPase demonstrated temperature dependence but differed in temperature optima. Temperature induced changes in specific activity of (Na+ plus K+)-activated ATPase directly paralleled previously demonstrated temperature optima for bile secretion. These studies indicate that (Na+ plus K+)-activated ATPase is present in fractions of rat liver plasma membranes that are highly enriched in bile canaliculi and provide a model for further study of the effects of various physiological and chemical modifiers of bile secretion and cholestasis.", "contents": "Properties of (Na+ plus K+)-activated ATPase in rat liver plasma membranes enriched with bile canaliculi. Liver plasma membranes enriched in bile canaliculi were isolated from rat liver by a modification of the technique of Song et al. (J. Cell Biol. (1969) 41, 124-132) in order to study the possible role of ATPase in bile secretion. Optimum conditions for assaying (Na+ plus K+)-activated ATPase in this membrane fraction were defined using male rats averaging 220 g in weight. (Na+ plus K+)-activated ATPase activity was documented by demonstrating specific cation requirements for Na+ and K+, while the divalent cation, Ca(2+), and the cardiac glycosides, ouabain and scillaren, were inhibitory. (Na+ plus K+)-activated ATPase activity averaged 10.07 plus or minus 2.80 mumol Pi/mg protein per h compared to 50.03 plus or minus 11.41 for Mg(2+)-activated ATPase and 58.66 plus or minus 10.07 for 5'-nucleotidase. Concentrations of ouabain and scillaren which previously inhibited canalicular bile secretion in the isolated perfused rat liver produced complete inhibition of (Na+ plus K+)-activated ATPase without any effect on Mg(2+)-activated ATPase. Both (Na+ plus K+)-activated ATPase and Mg(2+)-activated ATPase demonstrated temperature dependence but differed in temperature optima. Temperature induced changes in specific activity of (Na+ plus K+)-activated ATPase directly paralleled previously demonstrated temperature optima for bile secretion. These studies indicate that (Na+ plus K+)-activated ATPase is present in fractions of rat liver plasma membranes that are highly enriched in bile canaliculi and provide a model for further study of the effects of various physiological and chemical modifiers of bile secretion and cholestasis."}
{"id": "PMID:238661", "title": "The reaction of Rhodospirillum rubrum cytochrome c2 with iron hexacyanides.", "content": "The reaction of Rhodospirillum rubrum cytochrome c2 with the nonphysiological reactants, ferrocyanide and ferricyanide has been investigated as a function of ionic strength, temperature and pH, using both stopped-flow and temperature-jump kinetic methods. The results are consistent with a complex reaction mechanism involving the formation of two intermediate complexes. The site of electron transfer appears to be at the front of the cytochrome c2 molecule near the hem e crevice with interacton of both ferri and ferrocyanide with a positively charged region of the molecule. Comparison of the proposed electron transfer mechanism of cytochrome c2 with ferro-ferricyanide is made with the mechanism proposed based upon structural considerations.", "contents": "The reaction of Rhodospirillum rubrum cytochrome c2 with iron hexacyanides. The reaction of Rhodospirillum rubrum cytochrome c2 with the nonphysiological reactants, ferrocyanide and ferricyanide has been investigated as a function of ionic strength, temperature and pH, using both stopped-flow and temperature-jump kinetic methods. The results are consistent with a complex reaction mechanism involving the formation of two intermediate complexes. The site of electron transfer appears to be at the front of the cytochrome c2 molecule near the hem e crevice with interacton of both ferri and ferrocyanide with a positively charged region of the molecule. Comparison of the proposed electron transfer mechanism of cytochrome c2 with ferro-ferricyanide is made with the mechanism proposed based upon structural considerations."}
{"id": "PMID:238663", "title": "Ternary solvents to investigate proteins at zub-zero temperatures.", "content": "Mixtures of water, ethylene glycol and methanol in different volume ratios have been selected to carry out kinetics of enzyme reactions at sub-zero temperatures with the intention to reduce maximally the viscosity. Density, viscosity and dielectric constant values of these mixtures as a function of temperature are reported, as well as values of the protonic activity of several buffers under such conditions. A procedure to avoid or delay the eventual damaging effect of methanol on proteins is described.", "contents": "Ternary solvents to investigate proteins at zub-zero temperatures. Mixtures of water, ethylene glycol and methanol in different volume ratios have been selected to carry out kinetics of enzyme reactions at sub-zero temperatures with the intention to reduce maximally the viscosity. Density, viscosity and dielectric constant values of these mixtures as a function of temperature are reported, as well as values of the protonic activity of several buffers under such conditions. A procedure to avoid or delay the eventual damaging effect of methanol on proteins is described."}
{"id": "PMID:238664", "title": "[Purification and properties of an esterase excreted during sporulation of Bacillus subtilis].", "content": "After growth in Difco Nutrient Broth, several proteolytic enzymes are excreted by B. subtilis, Marburg strain, namely a metalloprotease and a seryl protease. We report here the purification and some biochemical properties of a third extracellular hydrolytic enzyme for which we propose the term of esterase. As the serylprotease, the esterase is a seryl enzyme endowed with both proteolytic and esterolytic activities. Nevertheless the esterase differs from serylprotease in many aspects. In particular, it is an acidic enzyme with a low proteolytic activity and a high esterolytic activity. Its specificity toward synthetic substrates is restricted. The enzyme is active only on esters of amino acids and particularly on those of tyrosine. With Bz Tyr O Et as substrate the esterase displays a maximum of activity between pH 7.2 and 8.1 with a Km of 1.3.10-minus 3 M at 30 degrees C. At the end of this work, two questions remain unanswered: 1) the origin of the multiplicity of the bands revealed by polyacrylamide electrophoresis in the purest fraction; 2) the nature of the physiological substrate of the enzyme.", "contents": "[Purification and properties of an esterase excreted during sporulation of Bacillus subtilis]. After growth in Difco Nutrient Broth, several proteolytic enzymes are excreted by B. subtilis, Marburg strain, namely a metalloprotease and a seryl protease. We report here the purification and some biochemical properties of a third extracellular hydrolytic enzyme for which we propose the term of esterase. As the serylprotease, the esterase is a seryl enzyme endowed with both proteolytic and esterolytic activities. Nevertheless the esterase differs from serylprotease in many aspects. In particular, it is an acidic enzyme with a low proteolytic activity and a high esterolytic activity. Its specificity toward synthetic substrates is restricted. The enzyme is active only on esters of amino acids and particularly on those of tyrosine. With Bz Tyr O Et as substrate the esterase displays a maximum of activity between pH 7.2 and 8.1 with a Km of 1.3.10-minus 3 M at 30 degrees C. At the end of this work, two questions remain unanswered: 1) the origin of the multiplicity of the bands revealed by polyacrylamide electrophoresis in the purest fraction; 2) the nature of the physiological substrate of the enzyme."}
{"id": "PMID:238665", "title": "[Relationship between the structure and activity of a histamine-blocking serum glycoprotein].", "content": "A plasmatic glycoprotein is submitted to a mild periodate oxydation and its pharmacological activity is studied. This glycoprotein contains much N acetyl Neuraminic Acid (NANA = 15 p. cent), and it reduces the biological activity of histamine on smooth muscle such as guinea pig ileum. See article. We also identify the 8 NANA and 7 NANA derivaties. Th only 8 carbon derivative is obtained when about one mole of m-periodate is consumed for one mole of NANA. The 7 carbon derivative appears as soon as the consumption of a second mole leads ta a second cleavage. These results prove that the oxydation islimited to the sole N acetyl neuraminic acid and more precisely to the lateral polyhydroxylic chain. Under these conditions, pharmacological activity gradually decreases, it disappears as soon as the lateral polyhydroxylic chain is completely cut off.", "contents": "[Relationship between the structure and activity of a histamine-blocking serum glycoprotein]. A plasmatic glycoprotein is submitted to a mild periodate oxydation and its pharmacological activity is studied. This glycoprotein contains much N acetyl Neuraminic Acid (NANA = 15 p. cent), and it reduces the biological activity of histamine on smooth muscle such as guinea pig ileum. See article. We also identify the 8 NANA and 7 NANA derivaties. Th only 8 carbon derivative is obtained when about one mole of m-periodate is consumed for one mole of NANA. The 7 carbon derivative appears as soon as the consumption of a second mole leads ta a second cleavage. These results prove that the oxydation islimited to the sole N acetyl neuraminic acid and more precisely to the lateral polyhydroxylic chain. Under these conditions, pharmacological activity gradually decreases, it disappears as soon as the lateral polyhydroxylic chain is completely cut off."}
{"id": "PMID:238666", "title": "Human granulocyte 6 phosphogluconate dehydrogenase. Purification by elective elution with NADP+, immunological and kinetic properties.", "content": "Human granulocyte 6 phosphogluconate dehydrogenase has been totally purified from a single patient with chronic granulocytic leukaemia. 48 mg of protein, of specific activity 20 IU per mg of protein, have been obtained in the course of three different steps only. The overall yield was 30 p. cent and the purification was 100 folds. Purified 6 phosphogluconate dehydrogenase was homogeneous when tested in acrylamide and acrylamide SDS gel electrophoresis or in immunodiffusion. The enzyme was immunologically identical in red blood cells, blood platelets and normal leukocytes. The fixation of both substrates, NADP-+ and 6 phosphogluconate, seemed to proceed through a non ordered mechanism. NADPH was an inhibitor strictly competitive with respect to NADP-+ and non competitive with respect to 6 phosphogluconate. 2-3 Diphosphoglycerate seemed to be able to bind on both the fixation sites of NADP-+ and 6 phosphogluconate. The inhibition by ATP was competitive with 6 phosphogluconate and non competitive with NADP-+. 6 phosphogluconate dehydrogenase was inactivated by SH reagents and was partially protected against this inactivation by both substrates. Both substrates protected the enzyme against thermal inactivation. The influence of ionic strength, pH and ions have been studied, and the results have been compared to those reported by other authors for erythrocyte enzyme.", "contents": "Human granulocyte 6 phosphogluconate dehydrogenase. Purification by elective elution with NADP+, immunological and kinetic properties. Human granulocyte 6 phosphogluconate dehydrogenase has been totally purified from a single patient with chronic granulocytic leukaemia. 48 mg of protein, of specific activity 20 IU per mg of protein, have been obtained in the course of three different steps only. The overall yield was 30 p. cent and the purification was 100 folds. Purified 6 phosphogluconate dehydrogenase was homogeneous when tested in acrylamide and acrylamide SDS gel electrophoresis or in immunodiffusion. The enzyme was immunologically identical in red blood cells, blood platelets and normal leukocytes. The fixation of both substrates, NADP-+ and 6 phosphogluconate, seemed to proceed through a non ordered mechanism. NADPH was an inhibitor strictly competitive with respect to NADP-+ and non competitive with respect to 6 phosphogluconate. 2-3 Diphosphoglycerate seemed to be able to bind on both the fixation sites of NADP-+ and 6 phosphogluconate. The inhibition by ATP was competitive with 6 phosphogluconate and non competitive with NADP-+. 6 phosphogluconate dehydrogenase was inactivated by SH reagents and was partially protected against this inactivation by both substrates. Both substrates protected the enzyme against thermal inactivation. The influence of ionic strength, pH and ions have been studied, and the results have been compared to those reported by other authors for erythrocyte enzyme."}
{"id": "PMID:238667", "title": "[Oxidation of erucic acid and erucyl-CoA by isolated rat heart mitochondria: comparison to oleic acid].", "content": "The oxidation of [14 14-C] or [1 14-C] erucic acid by isolated mitochondria from Rat heart has been studied and compared with that of [10 14-C] oleic acid in varying conditions of incubation. Erucic acid is converted to CO2 and acid-soluble compounds much more slowly than oleic acid. The acid-soluble compounds which have been identified are acylcarnitines, ketone bodies and intermediates from the Krebs cycle; they are found in similar proportions for both substrates. Moreover, the oxidation rate of erucyl-CoA is comparable, if not equal, to that of oleyl-CoA in the same conditions. These results are discussed here. They lead to the conclusion that erucic acid is oxidized by isolated Rat heart mitochondria through the beta oxidation pathway, and that its oxidation is limited owing to its slow activation rate.", "contents": "[Oxidation of erucic acid and erucyl-CoA by isolated rat heart mitochondria: comparison to oleic acid]. The oxidation of [14 14-C] or [1 14-C] erucic acid by isolated mitochondria from Rat heart has been studied and compared with that of [10 14-C] oleic acid in varying conditions of incubation. Erucic acid is converted to CO2 and acid-soluble compounds much more slowly than oleic acid. The acid-soluble compounds which have been identified are acylcarnitines, ketone bodies and intermediates from the Krebs cycle; they are found in similar proportions for both substrates. Moreover, the oxidation rate of erucyl-CoA is comparable, if not equal, to that of oleyl-CoA in the same conditions. These results are discussed here. They lead to the conclusion that erucic acid is oxidized by isolated Rat heart mitochondria through the beta oxidation pathway, and that its oxidation is limited owing to its slow activation rate."}
{"id": "PMID:238668", "title": "Application of Raman spectroscopy to biological macromolecules.", "content": "The Raman spectra of biological macromolecules arise from molecular vibrations of either the backbone chains or the side chains. The frequencies of the Raman bands lie in a region between 200 cm-1 and 3000 cm-1. From certain frequencies of the vibrations of the backbone chains one can determine the conformation or secondary structure of a macromolecule. Thus for polypeptides and proteins the frequencies of the Amide I and Amide III vibrations allow one to determine the averge conformation of their backbone chain. In polynucleotides and nucleic acids, the frequency of the phosphate diester stretch of the phosphate furanose chain varies between 814 cm-1 for A conformation and 790 cm-1 for B conformation. Raman spectra of the bases in nucleic acids can be used to determine base stacking and hydrogen bonding interactions. Thus Raman spectroscopy is an important tool for determining the conformation structure of proteins and nucleic acids.", "contents": "Application of Raman spectroscopy to biological macromolecules. The Raman spectra of biological macromolecules arise from molecular vibrations of either the backbone chains or the side chains. The frequencies of the Raman bands lie in a region between 200 cm-1 and 3000 cm-1. From certain frequencies of the vibrations of the backbone chains one can determine the conformation or secondary structure of a macromolecule. Thus for polypeptides and proteins the frequencies of the Amide I and Amide III vibrations allow one to determine the averge conformation of their backbone chain. In polynucleotides and nucleic acids, the frequency of the phosphate diester stretch of the phosphate furanose chain varies between 814 cm-1 for A conformation and 790 cm-1 for B conformation. Raman spectra of the bases in nucleic acids can be used to determine base stacking and hydrogen bonding interactions. Thus Raman spectroscopy is an important tool for determining the conformation structure of proteins and nucleic acids."}
{"id": "PMID:238669", "title": "Fatty acid composition of some cellular membranes of fetal rat liver.", "content": "The fatty acid composition of lipids of inner mitochondrial membrane, rough and smooth endoplasmic reticulum of adult and fetal rat liver has been determined. Subcellular membranes of fetal liver show a higher content of palmitic acid and oleic acid and a lower content of stearic acid and arachidonic acid as compared to subcellular membranes of the adult liver. The activity of citrate lyase and acetyl-CoA carboxylase of rat liver cytosol has been determined as a function of age. It is concluded that the differences are due to a relative deficiency of the fatty acid elongation system. The higher degree of saturation of the fatty acids of the phospholipids of the fetal membranes may be the cause of altered permeability properties of these membranes, as illustrated by the slower rate of isoosmotic swelling in the presence of the ammonium salt of some of the Krebs cycle intermediates in fetal rat liver mitochondria.", "contents": "Fatty acid composition of some cellular membranes of fetal rat liver. The fatty acid composition of lipids of inner mitochondrial membrane, rough and smooth endoplasmic reticulum of adult and fetal rat liver has been determined. Subcellular membranes of fetal liver show a higher content of palmitic acid and oleic acid and a lower content of stearic acid and arachidonic acid as compared to subcellular membranes of the adult liver. The activity of citrate lyase and acetyl-CoA carboxylase of rat liver cytosol has been determined as a function of age. It is concluded that the differences are due to a relative deficiency of the fatty acid elongation system. The higher degree of saturation of the fatty acids of the phospholipids of the fetal membranes may be the cause of altered permeability properties of these membranes, as illustrated by the slower rate of isoosmotic swelling in the presence of the ammonium salt of some of the Krebs cycle intermediates in fetal rat liver mitochondria."}
{"id": "PMID:238670", "title": "Fetal asphyxia due to umbilical cord compression. Metabolic and brain pathologic consequences.", "content": "Term monkey fetus 1620 sustained 50 min of rapidly developing severe asphyxia which began immediately after its in utero version. The arterial blood pO2 decreased from a normal value of 34 to 11-12 mm Hg while the blood pH fell from 7.35 to 6.70. During this asphyxia, hemoglobin-oxygen saturations below 5% were recorded. The complete collapse of the umbilical circulation several minutes prior to the reoxygenation of the fetus added an episode of total asphyxia. With reoxygenation following delivery, fetal cardiovascular performance improved rapidly though over an hour was required for recovery from the severe acidosis. The animal prospered but was found moribund on the 13th postnatal day due to dehydration. Brain examination after euthanasia revealed severe paracentral cortical and basal ganglia damage. Damage also appeared symmetrically in nuclei in the lower brain stem and in thalamus. These three zones of injury are attributed to the partial, the partial combined with the total, and the total asphyxia, respectively. The present case makes clear that compression of the umbilical cord may cause damage of a variety of types depending on the severity and duration of the asphyxia induced. It also demonstrates the possibility of recovery from a systemic acidosis where the pH values have fallen to levels below 6.70 for up to an hour.", "contents": "Fetal asphyxia due to umbilical cord compression. Metabolic and brain pathologic consequences. Term monkey fetus 1620 sustained 50 min of rapidly developing severe asphyxia which began immediately after its in utero version. The arterial blood pO2 decreased from a normal value of 34 to 11-12 mm Hg while the blood pH fell from 7.35 to 6.70. During this asphyxia, hemoglobin-oxygen saturations below 5% were recorded. The complete collapse of the umbilical circulation several minutes prior to the reoxygenation of the fetus added an episode of total asphyxia. With reoxygenation following delivery, fetal cardiovascular performance improved rapidly though over an hour was required for recovery from the severe acidosis. The animal prospered but was found moribund on the 13th postnatal day due to dehydration. Brain examination after euthanasia revealed severe paracentral cortical and basal ganglia damage. Damage also appeared symmetrically in nuclei in the lower brain stem and in thalamus. These three zones of injury are attributed to the partial, the partial combined with the total, and the total asphyxia, respectively. The present case makes clear that compression of the umbilical cord may cause damage of a variety of types depending on the severity and duration of the asphyxia induced. It also demonstrates the possibility of recovery from a systemic acidosis where the pH values have fallen to levels below 6.70 for up to an hour."}
{"id": "PMID:238671", "title": "Membrane lipid, not polarized water, is responsible for the semipermeable properties of living cells.", "content": "It has recently been proposed that the semipermeable surface barrier of living cells is in fact provided by water polarized in multilayers by the cellular protein, and not by the lipids of the cell membrane as had been widely supposed. This review paper summarizes a large and diverse body of recent experimental work, concerned with the structure and function of biological membranes in general and with the passive permeability properties of cell surface membranes in particular, which does not support the polarized water hypothesis. Indeed, there exists a great deal of experimental evidence which supports the concept that the lipid bilayer is a central structural feature of cell surface membranes and that one of the major functions of this lipid bilayer is to provide the selective, semipermeable barrier found at the surface of living cells.", "contents": "Membrane lipid, not polarized water, is responsible for the semipermeable properties of living cells. It has recently been proposed that the semipermeable surface barrier of living cells is in fact provided by water polarized in multilayers by the cellular protein, and not by the lipids of the cell membrane as had been widely supposed. This review paper summarizes a large and diverse body of recent experimental work, concerned with the structure and function of biological membranes in general and with the passive permeability properties of cell surface membranes in particular, which does not support the polarized water hypothesis. Indeed, there exists a great deal of experimental evidence which supports the concept that the lipid bilayer is a central structural feature of cell surface membranes and that one of the major functions of this lipid bilayer is to provide the selective, semipermeable barrier found at the surface of living cells."}
{"id": "PMID:238672", "title": "Ionic strength dependence of the hysteresis in the polyriboadenylate-polyribouridylate system.", "content": "The hysteresis observed in cyclic acid-base titrations of the three-standed polyribonucleotide helix poly (A)-2 POLY (U) strongly depends on ionic strength. For NaCl and at 25 degrees C, hysteresis occurs in the limited concentration range between 0.03 M and 1.0 M(NaCl). The transition points associated with the cyclic conversions between the triple helix and the poly (A)-poly (A) double helix and (free) poly (U) constitute a (pH ionic strength) phase diagram covering the ranges of stability and metastability of the hysteresis system. Variations with  NaCl concentration of some hysteresis parameters can be quantitatively described in terms of polyelectrolyte theories based on the cylinder-cell model for rodlike polyions. The results of this analysis suggest that the metastability is predominantly due to dlectrostatic energy barriers preventing the equilibrium transition of the partially protonated triple helix above a critical pH value. Ultraviolet absorbance and potentiometric titration data of poly (A)in the acidic pH range can be analyzed in terms of two types of double-helical structures. Spectrophotometric titrations reveal isosbestic wavelengths for structural transitions of poly (A). \"Time effects\" commonly observed in poly (A) titrations are suggested to reflect helix transitions between the two acidic structures.", "contents": "Ionic strength dependence of the hysteresis in the polyriboadenylate-polyribouridylate system. The hysteresis observed in cyclic acid-base titrations of the three-standed polyribonucleotide helix poly (A)-2 POLY (U) strongly depends on ionic strength. For NaCl and at 25 degrees C, hysteresis occurs in the limited concentration range between 0.03 M and 1.0 M(NaCl). The transition points associated with the cyclic conversions between the triple helix and the poly (A)-poly (A) double helix and (free) poly (U) constitute a (pH ionic strength) phase diagram covering the ranges of stability and metastability of the hysteresis system. Variations with  NaCl concentration of some hysteresis parameters can be quantitatively described in terms of polyelectrolyte theories based on the cylinder-cell model for rodlike polyions. The results of this analysis suggest that the metastability is predominantly due to dlectrostatic energy barriers preventing the equilibrium transition of the partially protonated triple helix above a critical pH value. Ultraviolet absorbance and potentiometric titration data of poly (A)in the acidic pH range can be analyzed in terms of two types of double-helical structures. Spectrophotometric titrations reveal isosbestic wavelengths for structural transitions of poly (A). \"Time effects\" commonly observed in poly (A) titrations are suggested to reflect helix transitions between the two acidic structures."}
{"id": "PMID:238675", "title": "Immunodeficiency in the Wiskott-Aldrich syndrome.", "content": "The immune system in the Wiskott-Aldrich syndrome is characterized by a host of paradoxes. Elements of the effector limbs of both humoral and cellular immunity such as immunoglobulin synthesis and in vitro lymphocyte proliferative, secretory and killer responses to nonspecific mitogens are intact. Yet, these patients fail to produce specific antibody normally following immunization and they are anergic. This combination of findings is consistent with a defect in the appropriate initiation of specific immune responses, ie a defect in the afferent limb of immunity.", "contents": "Immunodeficiency in the Wiskott-Aldrich syndrome. The immune system in the Wiskott-Aldrich syndrome is characterized by a host of paradoxes. Elements of the effector limbs of both humoral and cellular immunity such as immunoglobulin synthesis and in vitro lymphocyte proliferative, secretory and killer responses to nonspecific mitogens are intact. Yet, these patients fail to produce specific antibody normally following immunization and they are anergic. This combination of findings is consistent with a defect in the appropriate initiation of specific immune responses, ie a defect in the afferent limb of immunity."}
{"id": "PMID:238676", "title": "Primary immunodeficiency and malignancy.", "content": "Evidence indicating an essential relationship between immunologic deviation and cancer has accumulated rapidly over the past 15 years. Following a brief review of the enormous body of literature linking experimental immunodeficiency and cancer, this discussion will center on humans with primary immunodeficiency disorders and the inordinate number of malignancies which develop in these patients.", "contents": "Primary immunodeficiency and malignancy. Evidence indicating an essential relationship between immunologic deviation and cancer has accumulated rapidly over the past 15 years. Following a brief review of the enormous body of literature linking experimental immunodeficiency and cancer, this discussion will center on humans with primary immunodeficiency disorders and the inordinate number of malignancies which develop in these patients."}
{"id": "PMID:238677", "title": "Increased susceptibility to infection in sickle cell disease: defects of opsonization and of splenic function.", "content": "Patients with sickle cell disease (SCD) have an increased susceptibility to bacterial infections and die more frequently from infection than any other cause. Their sera do not promote the phagocytosis of pneumococci normally, apparently because of an inability to utilize the alternate pathway for C3 fixation as a means of opsonization. The splenic dysfunction which exists in SCD may result in depressed synthesis of alternate pathway factor(s), as well as in decreased phagocytic clearance of bacteria.", "contents": "Increased susceptibility to infection in sickle cell disease: defects of opsonization and of splenic function. Patients with sickle cell disease (SCD) have an increased susceptibility to bacterial infections and die more frequently from infection than any other cause. Their sera do not promote the phagocytosis of pneumococci normally, apparently because of an inability to utilize the alternate pathway for C3 fixation as a means of opsonization. The splenic dysfunction which exists in SCD may result in depressed synthesis of alternate pathway factor(s), as well as in decreased phagocytic clearance of bacteria."}
{"id": "PMID:238678", "title": "Fetal thymus transplantation: experimental and clinical observations.", "content": "The murine fetal thymus obtained early in gestation was found to develop normally in a syngeneic host. In contrast to the adult thymus grafts, the fetal thymus did not undergo the early and marked necrosis following transplantation into syngeneic hosts. Indeed, the fetal thymus was as effective as the adult thymus in achieving immunologic reconstitution of neonatally thymectomized syngeneic mice, and superior to adult thymus, when transplanted into allogeneic hosts. Furthermore, the fetal thymus, unlike the adult thymus, did not induce graft-vs-host disease (GVH) in genetically susceptible neonatally thymectomized mice. These observations seem relevant to thymus transplantation in children with a congenital absence of the thymus. Transplantation of fetal thymus in a child with DiGeorge syndrome corrected the T-cell immunodeficiency, and led to a reduction toward normal of the B-cell population.", "contents": "Fetal thymus transplantation: experimental and clinical observations. The murine fetal thymus obtained early in gestation was found to develop normally in a syngeneic host. In contrast to the adult thymus grafts, the fetal thymus did not undergo the early and marked necrosis following transplantation into syngeneic hosts. Indeed, the fetal thymus was as effective as the adult thymus in achieving immunologic reconstitution of neonatally thymectomized syngeneic mice, and superior to adult thymus, when transplanted into allogeneic hosts. Furthermore, the fetal thymus, unlike the adult thymus, did not induce graft-vs-host disease (GVH) in genetically susceptible neonatally thymectomized mice. These observations seem relevant to thymus transplantation in children with a congenital absence of the thymus. Transplantation of fetal thymus in a child with DiGeorge syndrome corrected the T-cell immunodeficiency, and led to a reduction toward normal of the B-cell population."}
{"id": "PMID:238680", "title": "Transplantation of incompatible bone marrow in infants with severe combined immunodeficiency disease.", "content": "Our efforts to overcome the fatal GVH disease following transplantation of incompatible bone marrow have been: 1) isolation of patient in sterile laminar flow room, 2) elimination of bacterial flora from GI tract, 3) repeated infusions of plasma containing blocking antibodies, 4) selection of HL-A identical but unrelated donor from general population, 5) use of stem-cell fraction of bone marrow and 6) gradual transplantation of marrow (less than 0.01 ml) carefully aspirated, free of immunocompetent T-cell contamination. A mild form of GVH disease, partial reconstitution of immune function and hematologic chimera were noted in 2 patients, who survived 67 days and 125 days after transplantation. More recently, an infant with severe combined immunodeficiency disease (SCID) has been reconstituted immunologically using marrow from HL-A mismatched, mixed leukocytes culture (MLC) non-reactive donor. The gradual transplantation method may be a useful means of transplanting incompatible marrow in infants with SCID.", "contents": "Transplantation of incompatible bone marrow in infants with severe combined immunodeficiency disease. Our efforts to overcome the fatal GVH disease following transplantation of incompatible bone marrow have been: 1) isolation of patient in sterile laminar flow room, 2) elimination of bacterial flora from GI tract, 3) repeated infusions of plasma containing blocking antibodies, 4) selection of HL-A identical but unrelated donor from general population, 5) use of stem-cell fraction of bone marrow and 6) gradual transplantation of marrow (less than 0.01 ml) carefully aspirated, free of immunocompetent T-cell contamination. A mild form of GVH disease, partial reconstitution of immune function and hematologic chimera were noted in 2 patients, who survived 67 days and 125 days after transplantation. More recently, an infant with severe combined immunodeficiency disease (SCID) has been reconstituted immunologically using marrow from HL-A mismatched, mixed leukocytes culture (MLC) non-reactive donor. The gradual transplantation method may be a useful means of transplanting incompatible marrow in infants with SCID."}
{"id": "PMID:238681", "title": "Compatible bone marrow transplantation and immunologic reconstitution of combined immunodeficiency disease.", "content": "To date, bone marrow transplantation affords the only successful means of achieving full immunologic reconstitution of patients with severe combined immunodeficiency disease (SCID). We have achieved immunologic reconstitution in 6 of 7 SCID patients using marrow transplants from compatible sib donors. One child died of Pneumocystis carinii pneumonia following early immunologic reconstitution. A second child died of sepsis without evidence of engraftment, despite 3 marrow grafts, and a third died unexpectedly from massive aspiration pneumonia following complete immunologic reconstititon. Thus, in 4 of 7 children with SCID full and long-lasting immunologic reconstitution has been achieved by transplantation of marrow from matched sib donors. From these initial efforts, much has been learned, and it is clear that several factors, some of which remain poorly understood, may influence the outcome of marrow grafting. However, despite the difficulties encountered, bone marrow transplantation continues to hold real promise for correction of this otherwise fatal disease.", "contents": "Compatible bone marrow transplantation and immunologic reconstitution of combined immunodeficiency disease. To date, bone marrow transplantation affords the only successful means of achieving full immunologic reconstitution of patients with severe combined immunodeficiency disease (SCID). We have achieved immunologic reconstitution in 6 of 7 SCID patients using marrow transplants from compatible sib donors. One child died of Pneumocystis carinii pneumonia following early immunologic reconstitution. A second child died of sepsis without evidence of engraftment, despite 3 marrow grafts, and a third died unexpectedly from massive aspiration pneumonia following complete immunologic reconstititon. Thus, in 4 of 7 children with SCID full and long-lasting immunologic reconstitution has been achieved by transplantation of marrow from matched sib donors. From these initial efforts, much has been learned, and it is clear that several factors, some of which remain poorly understood, may influence the outcome of marrow grafting. However, despite the difficulties encountered, bone marrow transplantation continues to hold real promise for correction of this otherwise fatal disease."}
{"id": "PMID:238682", "title": "The use of stem-cell grafts in combined immune deficiencies.", "content": "In 10 cases of CID, acute GVH reaction could be avoided by the use of small numbers of purified stem-cell concentrates. In 3 cases treated with stem cells from nonidentical donors, moderate delayed GVH reaction occurred. Death occurred from complicating infections. Bacteriologic decontamination is recommended as an additional precaution for future cases. This recommendation is supported by findings in germfree, as well as in specifically decontaminated, mice grafted with allogeneic marrow following x-irradiation in which mortality does not occur even after conventionalization after a limited period.", "contents": "The use of stem-cell grafts in combined immune deficiencies. In 10 cases of CID, acute GVH reaction could be avoided by the use of small numbers of purified stem-cell concentrates. In 3 cases treated with stem cells from nonidentical donors, moderate delayed GVH reaction occurred. Death occurred from complicating infections. Bacteriologic decontamination is recommended as an additional precaution for future cases. This recommendation is supported by findings in germfree, as well as in specifically decontaminated, mice grafted with allogeneic marrow following x-irradiation in which mortality does not occur even after conventionalization after a limited period."}
{"id": "PMID:238683", "title": "Bone marrow transplantation in combined immunodeficiencies.", "content": "Correction of combined immunodeficiences was attempted in 4 patients. Attainment of lasting immunologic reconstitution was restricted to an HL-A identical graft. However, HL-A identity was not a safeguard against graft-vs-host reaction (GVHR). Failure of donor-host adaptation resulted in chronic GVHR. In unmatched grafts, alloimmune plasma was capable of only transient amelioration of GVHR. Alloimmune plasma prevented fatal GVHR in one patient receiving a HL-A semiidentical graft. However, no direct evidence for a T-cell engraftment was shown. The failure to prevent GVHR or to reverse an ongoing reaction in incompatible bone marrow transplantations demands a reappraisal of the conceptual approach to immunologic tolerance.", "contents": "Bone marrow transplantation in combined immunodeficiencies. Correction of combined immunodeficiences was attempted in 4 patients. Attainment of lasting immunologic reconstitution was restricted to an HL-A identical graft. However, HL-A identity was not a safeguard against graft-vs-host reaction (GVHR). Failure of donor-host adaptation resulted in chronic GVHR. In unmatched grafts, alloimmune plasma was capable of only transient amelioration of GVHR. Alloimmune plasma prevented fatal GVHR in one patient receiving a HL-A semiidentical graft. However, no direct evidence for a T-cell engraftment was shown. The failure to prevent GVHR or to reverse an ongoing reaction in incompatible bone marrow transplantations demands a reappraisal of the conceptual approach to immunologic tolerance."}
{"id": "PMID:238684", "title": "Transplantation in severe combined immunodeficiency disease with hl-a identical bone marrow.", "content": "The immunologic reconstitution of 7 patients with severe combined immunodeficiency disease was attempted with bone marrow transplantation from histoidentical donors. Four patients were successfully reconstituted and discharged from the hospital. Two patients died with sepsis. One patient died from a preexisting neurologic disease. All the patients who have been successfully reconstituted have had some degree of graft-vs-host disease. A dose of 50 x 10(6) nucleated bone marrow cells per kg seems necessary for successful engraftment. The use of density gradient separation had no advantage over whole, unfractionated bone marrow.", "contents": "Transplantation in severe combined immunodeficiency disease with hl-a identical bone marrow. The immunologic reconstitution of 7 patients with severe combined immunodeficiency disease was attempted with bone marrow transplantation from histoidentical donors. Four patients were successfully reconstituted and discharged from the hospital. Two patients died with sepsis. One patient died from a preexisting neurologic disease. All the patients who have been successfully reconstituted have had some degree of graft-vs-host disease. A dose of 50 x 10(6) nucleated bone marrow cells per kg seems necessary for successful engraftment. The use of density gradient separation had no advantage over whole, unfractionated bone marrow."}
{"id": "PMID:238685", "title": "Attempted immunologic reconstitution of patients with combined immune deficiency syndrome with bone marrow transplantation from histoincompatible donors.", "content": "The immunologic reconstitution from patients with combined immune deficiency syndrome was attempted with bone marrow transplantation from histoincompatible donors. None of the patients achieved long-term immunologic reconstitution. In all cases, the incompatible bone marrow was treated before transplantation. Physical separation of the stem and immunocompetent cells was attempted in 2 cases with the use of enhancing antibody in one of the attempts. The selective destruction of the immunocompetent bone marrow cells after specific stimulation was attempted in the last 2 cases.", "contents": "Attempted immunologic reconstitution of patients with combined immune deficiency syndrome with bone marrow transplantation from histoincompatible donors. The immunologic reconstitution from patients with combined immune deficiency syndrome was attempted with bone marrow transplantation from histoincompatible donors. None of the patients achieved long-term immunologic reconstitution. In all cases, the incompatible bone marrow was treated before transplantation. Physical separation of the stem and immunocompetent cells was attempted in 2 cases with the use of enhancing antibody in one of the attempts. The selective destruction of the immunocompetent bone marrow cells after specific stimulation was attempted in the last 2 cases."}
{"id": "PMID:238687", "title": "Genetic and cellular control of in vitro models of allograft reactivity.", "content": "In each species sufficently studied, a single genetic region, the major histocompatibility complex (MHC), controls the strong transplantation antigens. Recent evidence suggests that the genetic control of differences important in allograft phenomenon is more complex than previously realized. In addition to the two loci, alleles of which control serologically defined (SD) antigens, there are other loci the phenotypic products of which lead to T-lymphocyte activation in mixed leukocyte culture. These latter loci have been referred to as LD (or lymphocyte defined). There appears to be a physiologic interaction between these two loci in that the LD differences seem to be important in the initial recognitive phases of the allograft reaction; the SD differences (or products of genes very closely linked to those determining the SD antigens) are important as a target for cytotoxicity as studied by the cell-mediated lympholysis test.", "contents": "Genetic and cellular control of in vitro models of allograft reactivity. In each species sufficently studied, a single genetic region, the major histocompatibility complex (MHC), controls the strong transplantation antigens. Recent evidence suggests that the genetic control of differences important in allograft phenomenon is more complex than previously realized. In addition to the two loci, alleles of which control serologically defined (SD) antigens, there are other loci the phenotypic products of which lead to T-lymphocyte activation in mixed leukocyte culture. These latter loci have been referred to as LD (or lymphocyte defined). There appears to be a physiologic interaction between these two loci in that the LD differences seem to be important in the initial recognitive phases of the allograft reaction; the SD differences (or products of genes very closely linked to those determining the SD antigens) are important as a target for cytotoxicity as studied by the cell-mediated lympholysis test."}
{"id": "PMID:238688", "title": "Studies on the immune response of congenitally athymic (nude) mice.", "content": "The central role of the thymus in immunity was assessed in nude mice. Nudes failed to reject allografts and xenografts and to respond to foreign erythrocytes but responded normally to endotoxin and pneumococcal polysaccharide. Thymus reconstitution was demonstrated in vivo and in vitro whereas reconstitution with thymic humoral factors or polyanions was not detected. Coliform overgrowth and depressed IgA levels in nudes appeared to contribute to wasting. These data emphasize the need for thymus participation in many immune phenomena.", "contents": "Studies on the immune response of congenitally athymic (nude) mice. The central role of the thymus in immunity was assessed in nude mice. Nudes failed to reject allografts and xenografts and to respond to foreign erythrocytes but responded normally to endotoxin and pneumococcal polysaccharide. Thymus reconstitution was demonstrated in vivo and in vitro whereas reconstitution with thymic humoral factors or polyanions was not detected. Coliform overgrowth and depressed IgA levels in nudes appeared to contribute to wasting. These data emphasize the need for thymus participation in many immune phenomena."}
{"id": "PMID:238689", "title": "Heat labile opsonin system to pneumococcus.", "content": "Normal mammalian sera contain the heat labile opsonin system that promotes the phagocytosis of various microorganisms by polymorphonuclear leukocytes. Because the heat labile opsonin system is present in normal nonimmune sera and because it operates against various microorganisms in an apparently nonspecif manner, it is considered to play an important role during the early phase of an acute bacterial infection. The role of various factors participating in the heat labile opsonin system, and its in vivo significance are discussed.", "contents": "Heat labile opsonin system to pneumococcus. Normal mammalian sera contain the heat labile opsonin system that promotes the phagocytosis of various microorganisms by polymorphonuclear leukocytes. Because the heat labile opsonin system is present in normal nonimmune sera and because it operates against various microorganisms in an apparently nonspecif manner, it is considered to play an important role during the early phase of an acute bacterial infection. The role of various factors participating in the heat labile opsonin system, and its in vivo significance are discussed."}
{"id": "PMID:238690", "title": "Desferrioxamine B: reversible side effects of high daily doses.", "content": "16 patients with chronic liver or haematologic diseases were parenterally given various doses of Desferrioxamine B (DF). Each daily dose of DF (from 1 to 4 g) was given for a 7 days cycle. Liver, kidney and blood functions were investigated at the first and seventh day of each cycle, and 1 and 2 weeks after therapy was stopped. 1 g/day and 2 g/day had no side effects, with the exception of a fall of white blood cell (WBC) count in a single case on 2 g/day. 3 g/day (15 patients) were followed by rises of blood urea, creatinine, alkaline phosphatase and glutamyl-transpeptidase respectively in 4 cases, and by falls of WBC count in 3 cases. 4 g/day (9 patients) caused rises of creatinine, GPT and GOT (1 case) or LDH (1 case), while WBC count dropped in 4 cases. All changes were reversible within one-two weeks. These recorded changes were outside the range of pretreatment values as obtained over the previous four weeks.", "contents": "Desferrioxamine B: reversible side effects of high daily doses. 16 patients with chronic liver or haematologic diseases were parenterally given various doses of Desferrioxamine B (DF). Each daily dose of DF (from 1 to 4 g) was given for a 7 days cycle. Liver, kidney and blood functions were investigated at the first and seventh day of each cycle, and 1 and 2 weeks after therapy was stopped. 1 g/day and 2 g/day had no side effects, with the exception of a fall of white blood cell (WBC) count in a single case on 2 g/day. 3 g/day (15 patients) were followed by rises of blood urea, creatinine, alkaline phosphatase and glutamyl-transpeptidase respectively in 4 cases, and by falls of WBC count in 3 cases. 4 g/day (9 patients) caused rises of creatinine, GPT and GOT (1 case) or LDH (1 case), while WBC count dropped in 4 cases. All changes were reversible within one-two weeks. These recorded changes were outside the range of pretreatment values as obtained over the previous four weeks."}
{"id": "PMID:238693", "title": "The first isolations of eastern encephalitis, group C, and Guama group arboviruses from the Peruvian Amazon region of western South America.", "content": "Two strains of eastern encephalitis (EE) virus were isolated in the Amazon region of Peru near Pucallpa, Loreto Department, using sentinel hamsters. EE virus antibodies were found in healthy horses at both Pucallpa and Iquitos in the same Department. Fourteen group C and four Guama group arboviruses were recovered from sentenel hamsters and mosquitoes near Iquitos. The group C agents were Caraparu-Ossa, Marituba, and Oriboca-Itaqui viruses, and the Guama group agents were Bimiti virus. Besides providing a detailed account of these investigations, this article includes a current list of known arboviruses of the American tropics that can be detected with sentinel hamsters.", "contents": "The first isolations of eastern encephalitis, group C, and Guama group arboviruses from the Peruvian Amazon region of western South America. Two strains of eastern encephalitis (EE) virus were isolated in the Amazon region of Peru near Pucallpa, Loreto Department, using sentinel hamsters. EE virus antibodies were found in healthy horses at both Pucallpa and Iquitos in the same Department. Fourteen group C and four Guama group arboviruses were recovered from sentenel hamsters and mosquitoes near Iquitos. The group C agents were Caraparu-Ossa, Marituba, and Oriboca-Itaqui viruses, and the Guama group agents were Bimiti virus. Besides providing a detailed account of these investigations, this article includes a current list of known arboviruses of the American tropics that can be detected with sentinel hamsters."}
{"id": "PMID:238696", "title": "The action of aminophylline on the acutely transplanted dog heart: effect of alpha- and beta-adrenoceptor blockade.", "content": "1 Aminophylline inhibits the coronary vasodilator actions of adenosine. Our previous studies suggested that low dose infusions of aminophylline reduce coronary blood flow in the isolated heart. In the present study we investigated the actions of aminophylline on coronary blood flow and myocardial contractility in a transplanted heart model. Drugs were given by close coronary arterial infusion. 2 Aminophylline in low doses (200 mug/min) reduced coronary blood flow by 21 plus or minus 2% (mean plus or minus s.e. mean) but did not alter myocardial contractility or heart rate. Higher doses (500 and 1000 mug/min) increased coronary blood flow and myocardial contractility without changing heart rate. 3 Alpha-adrenoceptor blockade with phenoxybenzamine did not affect the response to a low dose of aminophylline (200 mug/min). 4 Propranolol in doses of 10 and 30mug/min blocked beta-adrenoceptors but did not change coronary blood flow. The higher dose reduced myocardial contractility. 5 The effects of a high dose of aminophylline (1000 mug/min) on coronary blood flow were not changed by either alpha- or beta-adrenoceptor blockade, although propranolol (30 mug/min) reduced the augmentation in myocardial contractility. 6 The results show that when given in doses which do not alter myocardial contractility, aminophylline reduces coronary blood flow in the isolated heart and that this is not mediated through an alpha-adrenoceptor mechanism. They also show that the increases in coronary blood flow and positive inotropic effects obtained with higher doses of aminophylline are not mediated through catecholamines and suggest that higher doses of aminophylline have a small direct coronary vasodilator action. The low dose vasoconstrictor response may be produced by inhibition of the coronary vasodilator action of locally produced adenosine.", "contents": "The action of aminophylline on the acutely transplanted dog heart: effect of alpha- and beta-adrenoceptor blockade. 1 Aminophylline inhibits the coronary vasodilator actions of adenosine. Our previous studies suggested that low dose infusions of aminophylline reduce coronary blood flow in the isolated heart. In the present study we investigated the actions of aminophylline on coronary blood flow and myocardial contractility in a transplanted heart model. Drugs were given by close coronary arterial infusion. 2 Aminophylline in low doses (200 mug/min) reduced coronary blood flow by 21 plus or minus 2% (mean plus or minus s.e. mean) but did not alter myocardial contractility or heart rate. Higher doses (500 and 1000 mug/min) increased coronary blood flow and myocardial contractility without changing heart rate. 3 Alpha-adrenoceptor blockade with phenoxybenzamine did not affect the response to a low dose of aminophylline (200 mug/min). 4 Propranolol in doses of 10 and 30mug/min blocked beta-adrenoceptors but did not change coronary blood flow. The higher dose reduced myocardial contractility. 5 The effects of a high dose of aminophylline (1000 mug/min) on coronary blood flow were not changed by either alpha- or beta-adrenoceptor blockade, although propranolol (30 mug/min) reduced the augmentation in myocardial contractility. 6 The results show that when given in doses which do not alter myocardial contractility, aminophylline reduces coronary blood flow in the isolated heart and that this is not mediated through an alpha-adrenoceptor mechanism. They also show that the increases in coronary blood flow and positive inotropic effects obtained with higher doses of aminophylline are not mediated through catecholamines and suggest that higher doses of aminophylline have a small direct coronary vasodilator action. The low dose vasoconstrictor response may be produced by inhibition of the coronary vasodilator action of locally produced adenosine."}
{"id": "PMID:238697", "title": "The selectivity of beta-adrenoceptor antagonists on cardiovascular and bronchodilator responses to isoprenaline in the anaesthetized dog.", "content": "1 The actions of five beta-adrenoceptor antagonists, chosen because of reported differences in their selectivities, were compared using the positive chronotropic, vasodepressor and bronchodilator responses to isoprenaline in anesthetized dogs. 2 Propranolol was a potent antagonist of the isoprenaline responses in all three systems. 3 Practolol and acebutolol (M & B 17,803) blocked the positive chronotropic responses to isoprenaline to a greater extent than the vasodepressor or bronchodilator responses. 4 Butoxamine and alpha-methyl dichloroisoprenaline showed the opposite selectivity, blocking the vasodepressor and bronchodilator responses to isoprenaline to a greater extent than positive chronotropic responses. However, both drugs were considerably less potent than the other antagonists studied and their selectivities were less clear-cut than those of practolol or acebutolol. 5 All the antagonists lowered the resting heart rate and to a lesser extent the diastolic blood pressure. The effects of propranolol, practolol and acebutolol on heart rate probably result from cardiac beta-adrenoceptor blockade. With butoxamine and alpha-methyl dichloro isoprenaline, however, the effects on heart rate probably result from a direct cardiodepressant action. 6 The relevance of the results to the problem of the sub-classification of beta-adrenoceptors is discussed.", "contents": "The selectivity of beta-adrenoceptor antagonists on cardiovascular and bronchodilator responses to isoprenaline in the anaesthetized dog. 1 The actions of five beta-adrenoceptor antagonists, chosen because of reported differences in their selectivities, were compared using the positive chronotropic, vasodepressor and bronchodilator responses to isoprenaline in anesthetized dogs. 2 Propranolol was a potent antagonist of the isoprenaline responses in all three systems. 3 Practolol and acebutolol (M & B 17,803) blocked the positive chronotropic responses to isoprenaline to a greater extent than the vasodepressor or bronchodilator responses. 4 Butoxamine and alpha-methyl dichloroisoprenaline showed the opposite selectivity, blocking the vasodepressor and bronchodilator responses to isoprenaline to a greater extent than positive chronotropic responses. However, both drugs were considerably less potent than the other antagonists studied and their selectivities were less clear-cut than those of practolol or acebutolol. 5 All the antagonists lowered the resting heart rate and to a lesser extent the diastolic blood pressure. The effects of propranolol, practolol and acebutolol on heart rate probably result from cardiac beta-adrenoceptor blockade. With butoxamine and alpha-methyl dichloro isoprenaline, however, the effects on heart rate probably result from a direct cardiodepressant action. 6 The relevance of the results to the problem of the sub-classification of beta-adrenoceptors is discussed."}
{"id": "PMID:238698", "title": "The inhibitory action of oestradiol-17-beta and progesterone on venous smooth muscle.", "content": "1 The in vitro action of oestradiol-17-beta (0.1, 1.0 and 10.0 mug/ml) and progesterone (0.1, 1.0 and 10.0 mug/ml) on the spontaneous activity of the portal veins in female rats at different stages of gestation was studied. 2 Progesterone caused the spontaneous mechanical activity in the rat portal vein to decrease in amplitude and increase in frequency. This action was dose-dependent and the sensitivity of the tissue decreased throughout pregnancy. 3 Oestradiol-17-beta had a biphasic effect on spontaneous mechanical activity in the rat portal vein. At 0.1 mug/ml the vessel was stimulated while a similar effect to progesterone occurred with higher concentrations. The tissue was more sensitive to oestradiol at 7 days of gestation than at either the 10-14 or 17-21 day periods of gestation. 4 These effects of oestradiol and progesterone were still  seen after blockade of the beta-adrenoceptors. 5 Hydrocortisone (10 mug/ml) had no inhibitory effect on the spontaneous mechanical activity of the vein. 6 The veins from the 17-21 days pregnant animals showed a smaller amplitude of contraction than comparable non-pregnant females.", "contents": "The inhibitory action of oestradiol-17-beta and progesterone on venous smooth muscle. 1 The in vitro action of oestradiol-17-beta (0.1, 1.0 and 10.0 mug/ml) and progesterone (0.1, 1.0 and 10.0 mug/ml) on the spontaneous activity of the portal veins in female rats at different stages of gestation was studied. 2 Progesterone caused the spontaneous mechanical activity in the rat portal vein to decrease in amplitude and increase in frequency. This action was dose-dependent and the sensitivity of the tissue decreased throughout pregnancy. 3 Oestradiol-17-beta had a biphasic effect on spontaneous mechanical activity in the rat portal vein. At 0.1 mug/ml the vessel was stimulated while a similar effect to progesterone occurred with higher concentrations. The tissue was more sensitive to oestradiol at 7 days of gestation than at either the 10-14 or 17-21 day periods of gestation. 4 These effects of oestradiol and progesterone were still  seen after blockade of the beta-adrenoceptors. 5 Hydrocortisone (10 mug/ml) had no inhibitory effect on the spontaneous mechanical activity of the vein. 6 The veins from the 17-21 days pregnant animals showed a smaller amplitude of contraction than comparable non-pregnant females."}
{"id": "PMID:238695", "title": "[Glycolytic metabolism during muscular excerise in chronic broncho-pulmonary disease without hypoxemia (author's transl)].", "content": "Maximum oxygen uptake (VO2 max) was measured in 11 chronic bronchitics without heart failure or hypoxemia at rest and during maximal work load, using a triangular type of excerise with increasing power (30 W/3 min). Glycolysis was studied in these patients during rectangular exercises lasting 10 minutes, in which power was increased by steps from an average value of 45 % to 72 and 94 % of VO2 max. The metabolic response of lactate in blood is similar to normal, during the limited performances of these patients.", "contents": "[Glycolytic metabolism during muscular excerise in chronic broncho-pulmonary disease without hypoxemia (author's transl)]. Maximum oxygen uptake (VO2 max) was measured in 11 chronic bronchitics without heart failure or hypoxemia at rest and during maximal work load, using a triangular type of excerise with increasing power (30 W/3 min). Glycolysis was studied in these patients during rectangular exercises lasting 10 minutes, in which power was increased by steps from an average value of 45 % to 72 and 94 % of VO2 max. The metabolic response of lactate in blood is similar to normal, during the limited performances of these patients."}
{"id": "PMID:238699", "title": "Pharmacological  studies on surugatoxin, the toxic principle from Japanese ivory mollusc (Babylonia japonica).", "content": "1 Some pharmacological properties of surugatoxin (SGTX), a purified toxic substance from the Japanese ivory mollusc (Babylonia japonica), have been investigated. SGTX (50 nmol/kg i.v.) produced a prolonged fall of blood pressure in anaesthetized cats. This hypotensive effect was neither blocked by atropine and propranolol nor by spinal cord transection. 2 SGTX (37-50 nmol/kg i.v.) inhibited the hypertensive and hypotensive response to 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) and to electrical stimulation of the splanchnic and vagal nerve, whereas it usually augmented the hypertensive response to adrenaline and to 4-(m-chlorophenylcarbamoyloxy)-2-butynyltrimethylammonium chloride (McN-A-343) in anaesthetized cats. 3 Close intra-arterial injection of SGTX (6.2-12.3 nmol/kg) to the superior cervical ganglion blocked the contractile response of the nictitating membrane to preganglionic stimulation of cervical sympathetic nerve or injected DMPP, but not to postganglionic stimulation or to injected adrenaline and McN-A-343. 4 SGTX affected neither the indirectly nor the directly stimulated response of the rat isolated phrenic nerve-diaphragm at concentrations less than 12.3 mum. 5 The effect of SGTX on the contractile response to some agonists and on the twitch response to transmural stimulation in the guinea-pig isolated ileum was investigated. At less than 12.3 mumSGTX did not depress responses to acetylcholine or histamine. The curves for nicotine- and DMPP-induced contractions were shifted to the right and depressed gradually as the concentration of SGTX was increased (12.3 nm-1.23 mum). SGTX partially inhibited the contraction induced by 5-hyroxytryptamine and the transmurally-stimulated twitch response. 6 These results suggest that SGTX has a ganglion-blocking action. The mode of anti-nicotinic action of SGTX in the guinea-pig isolated ileum seems to differ from that of hexamethonium and tetraethylammonium and to resemble more closely that of mecamylamine.", "contents": "Pharmacological  studies on surugatoxin, the toxic principle from Japanese ivory mollusc (Babylonia japonica). 1 Some pharmacological properties of surugatoxin (SGTX), a purified toxic substance from the Japanese ivory mollusc (Babylonia japonica), have been investigated. SGTX (50 nmol/kg i.v.) produced a prolonged fall of blood pressure in anaesthetized cats. This hypotensive effect was neither blocked by atropine and propranolol nor by spinal cord transection. 2 SGTX (37-50 nmol/kg i.v.) inhibited the hypertensive and hypotensive response to 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) and to electrical stimulation of the splanchnic and vagal nerve, whereas it usually augmented the hypertensive response to adrenaline and to 4-(m-chlorophenylcarbamoyloxy)-2-butynyltrimethylammonium chloride (McN-A-343) in anaesthetized cats. 3 Close intra-arterial injection of SGTX (6.2-12.3 nmol/kg) to the superior cervical ganglion blocked the contractile response of the nictitating membrane to preganglionic stimulation of cervical sympathetic nerve or injected DMPP, but not to postganglionic stimulation or to injected adrenaline and McN-A-343. 4 SGTX affected neither the indirectly nor the directly stimulated response of the rat isolated phrenic nerve-diaphragm at concentrations less than 12.3 mum. 5 The effect of SGTX on the contractile response to some agonists and on the twitch response to transmural stimulation in the guinea-pig isolated ileum was investigated. At less than 12.3 mumSGTX did not depress responses to acetylcholine or histamine. The curves for nicotine- and DMPP-induced contractions were shifted to the right and depressed gradually as the concentration of SGTX was increased (12.3 nm-1.23 mum). SGTX partially inhibited the contraction induced by 5-hyroxytryptamine and the transmurally-stimulated twitch response. 6 These results suggest that SGTX has a ganglion-blocking action. The mode of anti-nicotinic action of SGTX in the guinea-pig isolated ileum seems to differ from that of hexamethonium and tetraethylammonium and to resemble more closely that of mecamylamine."}
{"id": "PMID:238700", "title": "The effects of burimamide and metiamide on basal gastric function in the cat.", "content": "1 Burimamide injected intravenously in the anaesthetized or conscious cat produced significant increases in gastric acid secretion: in the anaesthetized cat it produced increased gastric mucosal blood flow. 2 Metiamide, in doses which inhibited pentagastrin-stimulated acid secretion, produced no increase in gastric acid secretion in conscious animals, or gastric acid secretion or gastric mucosal blood flow in the anaesthetized cat. 3 Metiamide did not influence the amount of acid which diffused out of the stomach when instilled at pH values between 1.5 and 6.0. 4 The possible mode of action of burimamide in increasing basal gastric secretion is discussed.", "contents": "The effects of burimamide and metiamide on basal gastric function in the cat. 1 Burimamide injected intravenously in the anaesthetized or conscious cat produced significant increases in gastric acid secretion: in the anaesthetized cat it produced increased gastric mucosal blood flow. 2 Metiamide, in doses which inhibited pentagastrin-stimulated acid secretion, produced no increase in gastric acid secretion in conscious animals, or gastric acid secretion or gastric mucosal blood flow in the anaesthetized cat. 3 Metiamide did not influence the amount of acid which diffused out of the stomach when instilled at pH values between 1.5 and 6.0. 4 The possible mode of action of burimamide in increasing basal gastric secretion is discussed."}
{"id": "PMID:238701", "title": "E. coli endotoxin shock in the cat; treatment with indomethacin.", "content": "1. An earlier study had demonstrated that indomethacin, administered before E. coli endotoxin, abolished the initial pulmonary vasoconstriction and delayed the onset of the secondary shock phase that results from the intravenous injection of this agent in cats. The object of the present study was to determine whether indomethacin modified the shock phase when administered after endotoxin. 2. All the cats (whether or not they received indomethacin, 10 mg/kg) exhibited the characteristic features of the delayed shock phase that result from the administration of endotoxin (2 mg/kg). These included systemic hypotension, hypoglycaemia, reductions in arterial pH, cardiac output and systolic ejection time and an increase in arterial lactate. Five out of the ten animals given indomethacin survived 4 h compared with four out of twelve in the control (endotoxin along) group. 3. These results do not support the suggestion that antipyretic-analgesic drugs like indomethacin may be of benefit when given during bacteraemic or septic shock. They do support the suggestion that the acute pulmonary changes (hypertension and decreased compliance) that occur in this species within a few minutes of endotin administration ultimately contribute to the severity of the shock phase.", "contents": "E. coli endotoxin shock in the cat; treatment with indomethacin. 1. An earlier study had demonstrated that indomethacin, administered before E. coli endotoxin, abolished the initial pulmonary vasoconstriction and delayed the onset of the secondary shock phase that results from the intravenous injection of this agent in cats. The object of the present study was to determine whether indomethacin modified the shock phase when administered after endotoxin. 2. All the cats (whether or not they received indomethacin, 10 mg/kg) exhibited the characteristic features of the delayed shock phase that result from the administration of endotoxin (2 mg/kg). These included systemic hypotension, hypoglycaemia, reductions in arterial pH, cardiac output and systolic ejection time and an increase in arterial lactate. Five out of the ten animals given indomethacin survived 4 h compared with four out of twelve in the control (endotoxin along) group. 3. These results do not support the suggestion that antipyretic-analgesic drugs like indomethacin may be of benefit when given during bacteraemic or septic shock. They do support the suggestion that the acute pulmonary changes (hypertension and decreased compliance) that occur in this species within a few minutes of endotin administration ultimately contribute to the severity of the shock phase."}
{"id": "PMID:238702", "title": "The effects of catecholamines and adrenoceptor blocking drugs on the canine peripheral lymph flow.", "content": "Blood flow through the femoral artery, lymph flow in a lymphatic vessel in the femoral triangle and metatarsal distal venous pressure were measured simultaneously in a canine moving hind limb. 2. Low intra-arterial doses of adrenaline and noradrenaline increased lymph flow even in the presence of marked arterial vasoconstriction. In contrast, isoprenaline increased arterial blood flow without affecting lymph flow rate. 3. Phenoxybenzamine, dihydroergotoxine, and nicergoline did not inhibit the lymphatic flow increase induced by adrenaline at doses active on arterial or venous vascular alpha-adrenoceptors. 4. Propranolol given intra-arterially into animals pretreated with alpha-adrenoceptor blocking agents restored the vasoconstrictor effect of adrenaline (reversal of adrenaline reversal).", "contents": "The effects of catecholamines and adrenoceptor blocking drugs on the canine peripheral lymph flow. Blood flow through the femoral artery, lymph flow in a lymphatic vessel in the femoral triangle and metatarsal distal venous pressure were measured simultaneously in a canine moving hind limb. 2. Low intra-arterial doses of adrenaline and noradrenaline increased lymph flow even in the presence of marked arterial vasoconstriction. In contrast, isoprenaline increased arterial blood flow without affecting lymph flow rate. 3. Phenoxybenzamine, dihydroergotoxine, and nicergoline did not inhibit the lymphatic flow increase induced by adrenaline at doses active on arterial or venous vascular alpha-adrenoceptors. 4. Propranolol given intra-arterially into animals pretreated with alpha-adrenoceptor blocking agents restored the vasoconstrictor effect of adrenaline (reversal of adrenaline reversal)."}
{"id": "PMID:238703", "title": "The effect of propranolol on vascular responses to sympathetic nerve stimulation.", "content": "1. In an attempt to clarify the role of the sympathetic neurone in the antihypertensive action of propranolol, the effect of this drug on responses to lumbar sympathetic nerve stimulation has been studied in the perfused hind-limb of the dog. 2. No consistent reduction of maximal or submaximal responses to nerve stimulation was produced by propranolol (10 to 100 mug/kg). In contrast, potentiation of nerve-evoked response, as well as those to injected noradrenaline, usually occurred. Dexpropranolol (50 mug/kg) had no effect. 3. When neuronal uptake of noradrenaline was inhibited by desmethylimipramine or cacaine, no reduction in responses to sympathetic nerve stimulation was observed with propranolol. 4. No evidence was found, using alpha-adrenoceptor blocking drugs, that released transmitter stimulates beta-adrenoceptors in the blood vessels of the hind-limb. 5. No evidence has been found for the existence of an adrenergic neurone-blocking action of propranolol that might contribute to the antihypertensive activity in man.", "contents": "The effect of propranolol on vascular responses to sympathetic nerve stimulation. 1. In an attempt to clarify the role of the sympathetic neurone in the antihypertensive action of propranolol, the effect of this drug on responses to lumbar sympathetic nerve stimulation has been studied in the perfused hind-limb of the dog. 2. No consistent reduction of maximal or submaximal responses to nerve stimulation was produced by propranolol (10 to 100 mug/kg). In contrast, potentiation of nerve-evoked response, as well as those to injected noradrenaline, usually occurred. Dexpropranolol (50 mug/kg) had no effect. 3. When neuronal uptake of noradrenaline was inhibited by desmethylimipramine or cacaine, no reduction in responses to sympathetic nerve stimulation was observed with propranolol. 4. No evidence was found, using alpha-adrenoceptor blocking drugs, that released transmitter stimulates beta-adrenoceptors in the blood vessels of the hind-limb. 5. No evidence has been found for the existence of an adrenergic neurone-blocking action of propranolol that might contribute to the antihypertensive activity in man."}
{"id": "PMID:238704", "title": "Interaction of histamine H1-and H2-receptor antagonists with histamine uptake and metabolism by guinea-pig isolated atrium and mouse neoplastic mast cells cells in vitro.", "content": "1. Burimamide, metiamide, chlorpheniramine, triprolidine and cocaine, were tested as inhibitors of histamine uptake and metabolism in the guinea-pig atrium and in mouse neoplastic mast cells. 2. Cocaine did not affect the uptake and metabolism of histamine, either in the atrium or in the mast cells. All the antihistamines tested blocked the uptake and metabolism of histamine in both preparations. The order of potency was burimamide greater than chlorpheniramine greater than triprolidine greater than metiamide in the atrium; and burimamide greater than metiamide greater than triprolidine greater than chlorpheniramine, in the mase cells. 3. Comparison of the present results with the antihistamine activity of these blocking agents suggests that no correlation exists between the receptor blocking activity and the ability of these substances to act as inhibitors of histamine uptake and metabolism.", "contents": "Interaction of histamine H1-and H2-receptor antagonists with histamine uptake and metabolism by guinea-pig isolated atrium and mouse neoplastic mast cells cells in vitro. 1. Burimamide, metiamide, chlorpheniramine, triprolidine and cocaine, were tested as inhibitors of histamine uptake and metabolism in the guinea-pig atrium and in mouse neoplastic mast cells. 2. Cocaine did not affect the uptake and metabolism of histamine, either in the atrium or in the mast cells. All the antihistamines tested blocked the uptake and metabolism of histamine in both preparations. The order of potency was burimamide greater than chlorpheniramine greater than triprolidine greater than metiamide in the atrium; and burimamide greater than metiamide greater than triprolidine greater than chlorpheniramine, in the mase cells. 3. Comparison of the present results with the antihistamine activity of these blocking agents suggests that no correlation exists between the receptor blocking activity and the ability of these substances to act as inhibitors of histamine uptake and metabolism."}
{"id": "PMID:238705", "title": "Combined alpha- and beta-adrenoceptor blocking drug AH 5158: further studies on alpha-adrenoceptor blockade in anaesthetized animals.", "content": "1. AH 5158, 5-(1-hydroxy-2-((1-methyl-3-phenylpropyl)amino)ethyl)salicylamide, competitively antagonised phenylephrine-induced vasopressor responses in anaesthetized dogs, thus confirming that the drug possesses alpha-adrenoceptor blocking activity. 2. In contrast, AH 5158 was a relatively ineffective antagonist of vasopressor responses to noradrenaline in anesthetized dogs. Thus, at the lowest dose-level tested (1 mg/kg) AH 5158 abolished the increase in pulse width caused by noradrenaline, but otherwise had little or no blocking effect in doses as high as 10 mg/kg. Propranolol (0.1 mg/kg) also abolished the increase in pulse width caused by noradrenaline. With both drugs this effect is thought to be a consequence of blockade of the beta-adrenoceptor-mediated cardia stimulant action of noradrenaline. 3. The interaction between AH 5158 and noradrenaline in spinal dogs, anaesthetized cats and pithed rats was very similar to that seen in anaesthetized dogs. 4. Noradrenaline pressor responses were effectively antagonized by AH 5158 in anaesthetized dogs pretreated with cocaine. The degree of block was similar to that obtained when phenylephrine was the agonist in untreated dogs. 5. These results are consistent with the hypothesis that AH 5158 blocks a cocaine-sensitive inactivation process for noradrenaline in addition to blocking alpha- and beta-adrenoceptors. The resultant increase in the level of circulating noradrenaline would tend to counteract the adrenoceptor blocking action of the drug. 6. The implications of these findings are discussed.", "contents": "Combined alpha- and beta-adrenoceptor blocking drug AH 5158: further studies on alpha-adrenoceptor blockade in anaesthetized animals. 1. AH 5158, 5-(1-hydroxy-2-((1-methyl-3-phenylpropyl)amino)ethyl)salicylamide, competitively antagonised phenylephrine-induced vasopressor responses in anaesthetized dogs, thus confirming that the drug possesses alpha-adrenoceptor blocking activity. 2. In contrast, AH 5158 was a relatively ineffective antagonist of vasopressor responses to noradrenaline in anesthetized dogs. Thus, at the lowest dose-level tested (1 mg/kg) AH 5158 abolished the increase in pulse width caused by noradrenaline, but otherwise had little or no blocking effect in doses as high as 10 mg/kg. Propranolol (0.1 mg/kg) also abolished the increase in pulse width caused by noradrenaline. With both drugs this effect is thought to be a consequence of blockade of the beta-adrenoceptor-mediated cardia stimulant action of noradrenaline. 3. The interaction between AH 5158 and noradrenaline in spinal dogs, anaesthetized cats and pithed rats was very similar to that seen in anaesthetized dogs. 4. Noradrenaline pressor responses were effectively antagonized by AH 5158 in anaesthetized dogs pretreated with cocaine. The degree of block was similar to that obtained when phenylephrine was the agonist in untreated dogs. 5. These results are consistent with the hypothesis that AH 5158 blocks a cocaine-sensitive inactivation process for noradrenaline in addition to blocking alpha- and beta-adrenoceptors. The resultant increase in the level of circulating noradrenaline would tend to counteract the adrenoceptor blocking action of the drug. 6. The implications of these findings are discussed."}
{"id": "PMID:238706", "title": "Evidence for prostaglandin mediated prejunctional control of renal sympathetic transmitter release and vascular tone.", "content": "1 Prostaglandin E(2) dose-dependently and reversibly inhibited the noradrenaline overflow resulting from nerve stimulation of the rabbit kidney.2 The magnitude of this inhibition varied inversely with the frequency of stimulation employed.3 The prostaglandin synthesis inhibitors, indomethacin and meclofenamic acid, both increased the transmitter overflow resulting from renal nerve stimulation, suggesting that endogenous prostaglandin has a role in the regulation of transmitter release.4 In the presence of indomethacin, the inhibitory effect of exogenous prostaglandin E(2) was enhanced.5 The prostaglandin precursor, arachidonic acid, also caused a significant, dose-dependent and reversible inhibition of transmitter overflow. This inhibition became insignificant when arachidonic acid was applied in the presence of indomethacin, suggesting that the inhibition was mediated by newly formed prostaglandin rather than by arachidonic acid itself.6 It is proposed that newly formed prostaglandin controls noradrenaline release primarily from inner cortical nerve endings, thereby maintaining juxtamedullary blood flow under periods of increased sympathetic nerve activity.", "contents": "Evidence for prostaglandin mediated prejunctional control of renal sympathetic transmitter release and vascular tone. 1 Prostaglandin E(2) dose-dependently and reversibly inhibited the noradrenaline overflow resulting from nerve stimulation of the rabbit kidney.2 The magnitude of this inhibition varied inversely with the frequency of stimulation employed.3 The prostaglandin synthesis inhibitors, indomethacin and meclofenamic acid, both increased the transmitter overflow resulting from renal nerve stimulation, suggesting that endogenous prostaglandin has a role in the regulation of transmitter release.4 In the presence of indomethacin, the inhibitory effect of exogenous prostaglandin E(2) was enhanced.5 The prostaglandin precursor, arachidonic acid, also caused a significant, dose-dependent and reversible inhibition of transmitter overflow. This inhibition became insignificant when arachidonic acid was applied in the presence of indomethacin, suggesting that the inhibition was mediated by newly formed prostaglandin rather than by arachidonic acid itself.6 It is proposed that newly formed prostaglandin controls noradrenaline release primarily from inner cortical nerve endings, thereby maintaining juxtamedullary blood flow under periods of increased sympathetic nerve activity."}
{"id": "PMID:238711", "title": "Urinary lithiasis in childhood in the Bristol clinical area.", "content": "A series of 59 consecutive cases of urinary calculi in childhood is presented, being acquired from one local area (Bristol). These children were treated from 1950 to 1973. The peak presentation was in the 2nd and 3rd year of life, with a secondary peak in the 10th year. Anatomical (39%), metabolic (8.5%) or primary infective abnormalities (29%) were demonstrable, but 22% had to be left in an unsatisfactory \"idiopathic classification\". The overall recurrence rate of 7% was reduced to 3.5% when those patients with cystinuria were excluded. The local water supply areas have been studied and a tentative association is suggested between patients and their environment when they live in an area where the water is not only hard but also alkaline (pH greater than 8).", "contents": "Urinary lithiasis in childhood in the Bristol clinical area. A series of 59 consecutive cases of urinary calculi in childhood is presented, being acquired from one local area (Bristol). These children were treated from 1950 to 1973. The peak presentation was in the 2nd and 3rd year of life, with a secondary peak in the 10th year. Anatomical (39%), metabolic (8.5%) or primary infective abnormalities (29%) were demonstrable, but 22% had to be left in an unsatisfactory \"idiopathic classification\". The overall recurrence rate of 7% was reduced to 3.5% when those patients with cystinuria were excluded. The local water supply areas have been studied and a tentative association is suggested between patients and their environment when they live in an area where the water is not only hard but also alkaline (pH greater than 8)."}
{"id": "PMID:238712", "title": "Circulating immune complexes in schistosomiasis due to Schistosoma mansoni.", "content": "Immune complexes have been detected in the sera of people infected Schistosoma mansoni by the technique of acidification followed by double countercurrent immunoelectrophoresis in hypertonic buffered gels.", "contents": "Circulating immune complexes in schistosomiasis due to Schistosoma mansoni. Immune complexes have been detected in the sera of people infected Schistosoma mansoni by the technique of acidification followed by double countercurrent immunoelectrophoresis in hypertonic buffered gels."}
{"id": "PMID:238716", "title": "Effect of new beta-adrenergic blocking agent, Atenolol (Tenormin), on pain frequency, trinitrin consumption, and exercise ability.", "content": "In 11 patients with severe angina pectoris a new beta-blocking drug, atenolol (Tenormin; I.C.I.66082), was found in a double-blind randomized trial to reduce significantly the frequency of anginal attacks (P less than 0-001) and the amount of trinitrin consumed (P less than 0-03) in comparison with practolol and placebo. There was no significant improvement in the patients' ability to exercise on the bicycle ergometer.", "contents": "Effect of new beta-adrenergic blocking agent, Atenolol (Tenormin), on pain frequency, trinitrin consumption, and exercise ability. In 11 patients with severe angina pectoris a new beta-blocking drug, atenolol (Tenormin; I.C.I.66082), was found in a double-blind randomized trial to reduce significantly the frequency of anginal attacks (P less than 0-001) and the amount of trinitrin consumed (P less than 0-03) in comparison with practolol and placebo. There was no significant improvement in the patients' ability to exercise on the bicycle ergometer."}
{"id": "PMID:238718", "title": "Evidence of an incerto-hypothalamic dopamine neurone system in the rat.", "content": "With the recently introduced glyoxylic acid histochemical fluorescence method, a previously unknown catecholamine-containing fibre system has been revealed in the zona incerta, hypothalamus and the caudal septum. These fibres, designated the incerto-hypothalamic system, have a characteristic, very delicate, finely varicose appearance, and they have a weak fluorescence, indicating an unusually low intra-neuronal amine content. On the basis of their distribution a caudal and a rostral part can be discriminated: the caudal part extends from the area of the dopamine-containing cell bodies in the caudal thalamus, the posterior hypothalamic area and the medial zona incerta (the A11 and A13 cell groups) into the dorsal part of the dorso-medial nucleus and the dorsal and anterior hypothalamic areas; the rostral part extends from the area of the rostral periventricular dopaminergic cell system (the A14 cell group) into the medial preoptic area and the periventricular and suprachiasmatic preoptic nuclei. The system probably extends also into the most caudal portion of the lateral septal nucleus. From a series of lesions and in vitro uptake studies, evidence has been obtained that the incerto-hypothalamic fibres are the projections of short, intradiencephalic dopaminergic neurones whose cell bodies are located in the A11, A13 and A14 cell groups. The projection areas of these neurones signify an involvement of the system in the control of secretion of pituitary hormones.", "contents": "Evidence of an incerto-hypothalamic dopamine neurone system in the rat. With the recently introduced glyoxylic acid histochemical fluorescence method, a previously unknown catecholamine-containing fibre system has been revealed in the zona incerta, hypothalamus and the caudal septum. These fibres, designated the incerto-hypothalamic system, have a characteristic, very delicate, finely varicose appearance, and they have a weak fluorescence, indicating an unusually low intra-neuronal amine content. On the basis of their distribution a caudal and a rostral part can be discriminated: the caudal part extends from the area of the dopamine-containing cell bodies in the caudal thalamus, the posterior hypothalamic area and the medial zona incerta (the A11 and A13 cell groups) into the dorsal part of the dorso-medial nucleus and the dorsal and anterior hypothalamic areas; the rostral part extends from the area of the rostral periventricular dopaminergic cell system (the A14 cell group) into the medial preoptic area and the periventricular and suprachiasmatic preoptic nuclei. The system probably extends also into the most caudal portion of the lateral septal nucleus. From a series of lesions and in vitro uptake studies, evidence has been obtained that the incerto-hypothalamic fibres are the projections of short, intradiencephalic dopaminergic neurones whose cell bodies are located in the A11, A13 and A14 cell groups. The projection areas of these neurones signify an involvement of the system in the control of secretion of pituitary hormones."}
{"id": "PMID:238719", "title": "The catecholamine-containing tubero-infundibular system and the control of luteinizing hormone release in the rabbit.", "content": "As determined by fluorescence histochemistry, the distribution of catecholamine-containing neurons in the hypothalamus of the female rabbit is similar to that seen in the rat. The fluorescence appearance of the hypothalamus was not appreciably different from normal at 0.25, 1, 4 or 24 h after mating, but in animals in which the synthesis of catecholamines was inhibited by the administration of the tyrosine hydroxylase inhibitor, H44/68, the number of fluorescent neurons seen in the nucleus periventricularis arcuatus following copulation was markedly reduced. However, the concentrations of luteinizing hormone (LH) in serum and in the pituitary glands of mated and unmated animals treated with H44/68 were not significantly different from those found in the corresponding control animals. This, together with the fact that ovulation followed mating in drug-treated rabbits suggests that a normal level of catecholamines in the tubero-infundibular system is not essential for the secretion of the amount of LH necessary for ovulation.", "contents": "The catecholamine-containing tubero-infundibular system and the control of luteinizing hormone release in the rabbit. As determined by fluorescence histochemistry, the distribution of catecholamine-containing neurons in the hypothalamus of the female rabbit is similar to that seen in the rat. The fluorescence appearance of the hypothalamus was not appreciably different from normal at 0.25, 1, 4 or 24 h after mating, but in animals in which the synthesis of catecholamines was inhibited by the administration of the tyrosine hydroxylase inhibitor, H44/68, the number of fluorescent neurons seen in the nucleus periventricularis arcuatus following copulation was markedly reduced. However, the concentrations of luteinizing hormone (LH) in serum and in the pituitary glands of mated and unmated animals treated with H44/68 were not significantly different from those found in the corresponding control animals. This, together with the fact that ovulation followed mating in drug-treated rabbits suggests that a normal level of catecholamines in the tubero-infundibular system is not essential for the secretion of the amount of LH necessary for ovulation."}
{"id": "PMID:238720", "title": "Solubilization of 2',3'-cyclic nucleotide 3'-phosphohydrolase from bovine brain without detergents.", "content": "The enzyme in brain that hydrolyzes 2',3'-cyclic nucleotides to the 2'-mononucleotides has been found by several authors to be concentrated in the myelin fraction. To facilitate further study of the enzyme, one of our objectives has been to develop a method of solubilizing the enzyme without the use of detergents. When an acetone powder from brain white matter is homogenized with 1 M guanidinium chloride in 0.2 M buffer at pH 6, 10(-3) M in EDTA and in dithiothreitol, the enzyme is solubilized. If the guanidinium chloride is removed by dialysis in a single step, the enzyme reprecipitates, but if a fractional precipitation is performed by reducing the guanidinium chloride concentration by dilution, the enzyme remains in solution at 0.2 M guanidinium chloride. The precipitates obtained in this fractionation probably contain constituents which, at low salt concentration, formed a part of an insoluble aggregate, since after removal of the pellet the supernatant solution can be dialyzed free of guanidinium chloride without precipitating the enzymic activity. The enzyme thus prepared remains in the supernatant when centrifuged at 108,000 X g for 3 h and can be submitted to (NH4)2SO4 fractionation and chromatography on carboxymethyl-Sephadex and on hydroxylapatite. The enzyme has thereby been purified 200-fold in about 20% yield.", "contents": "Solubilization of 2',3'-cyclic nucleotide 3'-phosphohydrolase from bovine brain without detergents. The enzyme in brain that hydrolyzes 2',3'-cyclic nucleotides to the 2'-mononucleotides has been found by several authors to be concentrated in the myelin fraction. To facilitate further study of the enzyme, one of our objectives has been to develop a method of solubilizing the enzyme without the use of detergents. When an acetone powder from brain white matter is homogenized with 1 M guanidinium chloride in 0.2 M buffer at pH 6, 10(-3) M in EDTA and in dithiothreitol, the enzyme is solubilized. If the guanidinium chloride is removed by dialysis in a single step, the enzyme reprecipitates, but if a fractional precipitation is performed by reducing the guanidinium chloride concentration by dilution, the enzyme remains in solution at 0.2 M guanidinium chloride. The precipitates obtained in this fractionation probably contain constituents which, at low salt concentration, formed a part of an insoluble aggregate, since after removal of the pellet the supernatant solution can be dialyzed free of guanidinium chloride without precipitating the enzymic activity. The enzyme thus prepared remains in the supernatant when centrifuged at 108,000 X g for 3 h and can be submitted to (NH4)2SO4 fractionation and chromatography on carboxymethyl-Sephadex and on hydroxylapatite. The enzyme has thereby been purified 200-fold in about 20% yield."}
{"id": "PMID:238721", "title": "Interactions between lysergic acid diethylamide and dopamine-sensitive adenylate cyclase systems in rat brain.", "content": "Investigations were carried out on the interactions of the hallucinogenic drug, D-lysergic acid diethylamide (D-LSD), and other serotonin antagonists with catecholamine-sensitive adenylate cyclase systems in cell-free preparations from different regions of rat brain. In equimolar concentration, D-LSD, 2-brono-D-lysergic acid diethylamide (BOL), or methysergide (UML) strongly blocked maximal stimulation of adenylate cyclase activity by either norepinephrine or dopamine in particulate preparations from cerebral cortices of young adult rats. D-LSD also eliminated the stimulation of adenylate cyclase activity of equimolar concentrations of norepinephrine or dopamine in particulate preparations from rat hippocampus. The effects of this hallucinogenic agent on adenylate cyclase activity were most striking in particulate preparations from corpus striatum. Thus, in 10 muM concentration, D-LSD not only completely eradicated the response to 10 muM dopamine in these preparations but also consistently stimulated adenylate cyclase activity. L-LSD (80 muM) was without effect. Significant activation of striatal adenylate cyclase was produced by 0.1 muM D-LSD. Activation of striatal adenylate cyclase of either D-LSD or dopamine was strongly blocked by the dopamine-blocking agents trifluoperazine, thioridazine, chlorpromazine, and haloperidol. The stimulatory effects of D-LSD and dopamine were also inhibited by the serotonin-blocking agents, BOL, 1-methyl-D-lysergic acid diethylamide (MLD), and cyproheptadine, but not by the beta-adrenergic-blocking agent, propranolol. However, these serotonin antagonists by themselves were incapable of stimulating adenylate cyclase activity in the striatal preparations. Several other hallucinogens, which were structurally related to serotonin, were also inactive in this regard, e.g., mescaline, N,N-dimethyltryptamine, psilocin and bufotenine. Serotonin itself produced a small stimulation of adenylate cyclase activity in striatal preparations and, in relatively high concentration (100 muM), partially blocked the activation by 10 muM dopamine, but was without effect on the stimulation by 10 muM D-LSD. The present results indicate that serotonin antagonists, in general, are potent inhibitors of catecholamine-induced stimulation of adenylate cyclase systems in brain cell-free preparations. In addition, these results, coupled with earlier findings on the capacity of D-LSD to interact with serotonin-sensitive adenylate cyclase systems from rat brain23,24 and other neural systems16, strongly suggest that this hallucinogenic agent is capable of acting as an agonist at central dopamine and serotonin receptors, as well as functioning as an antagonist at dopamine, norepinephrine, and serotonin receptors in the brain.", "contents": "Interactions between lysergic acid diethylamide and dopamine-sensitive adenylate cyclase systems in rat brain. Investigations were carried out on the interactions of the hallucinogenic drug, D-lysergic acid diethylamide (D-LSD), and other serotonin antagonists with catecholamine-sensitive adenylate cyclase systems in cell-free preparations from different regions of rat brain. In equimolar concentration, D-LSD, 2-brono-D-lysergic acid diethylamide (BOL), or methysergide (UML) strongly blocked maximal stimulation of adenylate cyclase activity by either norepinephrine or dopamine in particulate preparations from cerebral cortices of young adult rats. D-LSD also eliminated the stimulation of adenylate cyclase activity of equimolar concentrations of norepinephrine or dopamine in particulate preparations from rat hippocampus. The effects of this hallucinogenic agent on adenylate cyclase activity were most striking in particulate preparations from corpus striatum. Thus, in 10 muM concentration, D-LSD not only completely eradicated the response to 10 muM dopamine in these preparations but also consistently stimulated adenylate cyclase activity. L-LSD (80 muM) was without effect. Significant activation of striatal adenylate cyclase was produced by 0.1 muM D-LSD. Activation of striatal adenylate cyclase of either D-LSD or dopamine was strongly blocked by the dopamine-blocking agents trifluoperazine, thioridazine, chlorpromazine, and haloperidol. The stimulatory effects of D-LSD and dopamine were also inhibited by the serotonin-blocking agents, BOL, 1-methyl-D-lysergic acid diethylamide (MLD), and cyproheptadine, but not by the beta-adrenergic-blocking agent, propranolol. However, these serotonin antagonists by themselves were incapable of stimulating adenylate cyclase activity in the striatal preparations. Several other hallucinogens, which were structurally related to serotonin, were also inactive in this regard, e.g., mescaline, N,N-dimethyltryptamine, psilocin and bufotenine. Serotonin itself produced a small stimulation of adenylate cyclase activity in striatal preparations and, in relatively high concentration (100 muM), partially blocked the activation by 10 muM dopamine, but was without effect on the stimulation by 10 muM D-LSD. The present results indicate that serotonin antagonists, in general, are potent inhibitors of catecholamine-induced stimulation of adenylate cyclase systems in brain cell-free preparations. In addition, these results, coupled with earlier findings on the capacity of D-LSD to interact with serotonin-sensitive adenylate cyclase systems from rat brain23,24 and other neural systems16, strongly suggest that this hallucinogenic agent is capable of acting as an agonist at central dopamine and serotonin receptors, as well as functioning as an antagonist at dopamine, norepinephrine, and serotonin receptors in the brain."}
{"id": "PMID:238722", "title": "The response of adrenergic neurones to axotomy and nerve growth factor.", "content": "Division of the axons of adrenergic neurones by crushing the postganglionic nerve trunks of rat superior cervical ganglia (SCG) at 6 days of age resulted in a permanent atrophy of the SCG reflected by a persistent decrease in the total protein content and in the activities of the enzymes tyrosine hydroxylase and DOPA decarboxylase. Administration of nerve growth factor (NGF) to rats with unilateral axotomy at a dose of 10 mug/g/day for the period 7-21 days of age resulted in hypertrophy of both normal and axotomised SCG. There was a progressive rise in the total protein content and in the activities of the two enzymes till the end of the treatment period in both SCG. After treatment ceased there was a progressive fall in the total protein content and activities of the two enzymes reaching a stable level after 4 weeks. The level reached for treated unoperated SCG remained elevated when compared to untreated control SCG. Axotomised treated SCG had approximately the same biochemical parameters as untreated control SCG and very much elevated over untreated axotomised SCG. These final levels persisted for at least 56 days after treatment had ceased. Animals showed a persistent ptosis after axotomy at 6 days of age but treatment with NGF resulted in a functional recovery by 11 weeks of age. It is suggested that there is normally a retrograde transfer of a factor durind development from the target cell to the perikarya of the neurone permitting survival if the appropriate connections are made. Failure to make such a contact results in cedd death. The cell death occurring normally, and the cell death resulting from axotomy, can both be prevented by NGF treatment leading to an hypertrophy of both SCG. This consistent with the hypothesis than NGF is the retrograde trophic agent for the sympathetic nervous system in the developing animal.", "contents": "The response of adrenergic neurones to axotomy and nerve growth factor. Division of the axons of adrenergic neurones by crushing the postganglionic nerve trunks of rat superior cervical ganglia (SCG) at 6 days of age resulted in a permanent atrophy of the SCG reflected by a persistent decrease in the total protein content and in the activities of the enzymes tyrosine hydroxylase and DOPA decarboxylase. Administration of nerve growth factor (NGF) to rats with unilateral axotomy at a dose of 10 mug/g/day for the period 7-21 days of age resulted in hypertrophy of both normal and axotomised SCG. There was a progressive rise in the total protein content and in the activities of the two enzymes till the end of the treatment period in both SCG. After treatment ceased there was a progressive fall in the total protein content and activities of the two enzymes reaching a stable level after 4 weeks. The level reached for treated unoperated SCG remained elevated when compared to untreated control SCG. Axotomised treated SCG had approximately the same biochemical parameters as untreated control SCG and very much elevated over untreated axotomised SCG. These final levels persisted for at least 56 days after treatment had ceased. Animals showed a persistent ptosis after axotomy at 6 days of age but treatment with NGF resulted in a functional recovery by 11 weeks of age. It is suggested that there is normally a retrograde transfer of a factor durind development from the target cell to the perikarya of the neurone permitting survival if the appropriate connections are made. Failure to make such a contact results in cedd death. The cell death occurring normally, and the cell death resulting from axotomy, can both be prevented by NGF treatment leading to an hypertrophy of both SCG. This consistent with the hypothesis than NGF is the retrograde trophic agent for the sympathetic nervous system in the developing animal."}
{"id": "PMID:238723", "title": "Some distinctive characteristics of the alkaline phosphatase of Serratia marcescens.", "content": "A mutant strain of Serratia marcescens produces a constitutive enzyme (phosphatase F), which differs from the alkaline phosphatase of Escherichia coli in the following characteristics: one enzyme species with higher mobility on electrophoresis, less heat stability, no rapid reactivation following exposure to high hydrogen ion concentrations, no hybridization with E. coli enzyme in vitro, little activation at increased ionic strength, greater sensitivity to EDTA inhibition, and no cross reaction of rabbit anti-serum with the E. coli enzyme.", "contents": "Some distinctive characteristics of the alkaline phosphatase of Serratia marcescens. A mutant strain of Serratia marcescens produces a constitutive enzyme (phosphatase F), which differs from the alkaline phosphatase of Escherichia coli in the following characteristics: one enzyme species with higher mobility on electrophoresis, less heat stability, no rapid reactivation following exposure to high hydrogen ion concentrations, no hybridization with E. coli enzyme in vitro, little activation at increased ionic strength, greater sensitivity to EDTA inhibition, and no cross reaction of rabbit anti-serum with the E. coli enzyme."}
{"id": "PMID:238724", "title": "Application of drug receptor theories to the analysis of the myotropic effects of bradykinin.", "content": "Cat jejunum and terminal ileum, and rat stomach strip and rat uterus contract to bradykinin, while rat duodenum relaxes. Dose-response curves of classical hyperbolic shape are obtained in the first three preparations, but not in the others. The negative logs of the drug concentrations which give 50% of the maximal response. (pD2) Values were, respectively, 7.68 and 7.77 in the cat jejunum and terminal ileum, 6.78 in the rat stomach strip and 8.64 in the rat uterus in estrus. Theoretical dose-response curves, constructed by using experimental pD2 values in the equation of Clark, (General pharmacology. Verlag Van J. Springer, Berlin, 1937), are superimposed to experimental curves, obtained in the cat jejunum and terminal ileum, but not in the rat stomach strip. This comparison was not made in the rat uterus and duodenum. The myotropic effect of bradykinin appears to be a direct one in the cat jejunum, the terminal ileum and the rat stomach strip, because it is not affected by anticholinergics, antiadrenergics, antihistaminics and indomethacin. pD2 values and the slope of the dose-response curves of the rat uterus were reduced by indomethacin. The results indicate that cat jejunum and terminal ileum are sensitive and specific for bradykinin and appear to be the most reliable preparations for studies on the structure-activity relationships of this peptide.", "contents": "Application of drug receptor theories to the analysis of the myotropic effects of bradykinin. Cat jejunum and terminal ileum, and rat stomach strip and rat uterus contract to bradykinin, while rat duodenum relaxes. Dose-response curves of classical hyperbolic shape are obtained in the first three preparations, but not in the others. The negative logs of the drug concentrations which give 50% of the maximal response. (pD2) Values were, respectively, 7.68 and 7.77 in the cat jejunum and terminal ileum, 6.78 in the rat stomach strip and 8.64 in the rat uterus in estrus. Theoretical dose-response curves, constructed by using experimental pD2 values in the equation of Clark, (General pharmacology. Verlag Van J. Springer, Berlin, 1937), are superimposed to experimental curves, obtained in the cat jejunum and terminal ileum, but not in the rat stomach strip. This comparison was not made in the rat uterus and duodenum. The myotropic effect of bradykinin appears to be a direct one in the cat jejunum, the terminal ileum and the rat stomach strip, because it is not affected by anticholinergics, antiadrenergics, antihistaminics and indomethacin. pD2 values and the slope of the dose-response curves of the rat uterus were reduced by indomethacin. The results indicate that cat jejunum and terminal ileum are sensitive and specific for bradykinin and appear to be the most reliable preparations for studies on the structure-activity relationships of this peptide."}
{"id": "PMID:238725", "title": "Natriuresis following fourth ventricle perfusion with high-sodium artificial CSF.", "content": "Perfusion of the fourth cerebral ventricle with high-sodium artificial cerebrospinal fluid was found to result in an increase in urinary sodium excretion in anesthetized cats. The natriuresis was accompanied by an increase in blood pressure and glomerular filtration rate. However, in animals with the changes in blood pressure and glomerular filtration rate prevented by alpha adrenergic blockade (phenoxybenzamine), the increase in urinary sodium excretion persisted. the data suggest the presence of a neural mechanism in the vicinity of the fourth ventricle sensitive to cerebrospinal fluid sodium levels and capable of affecting urinary sodium excretion independent of changes in blood pressure or glomerular filtration rate. The possible role of the area postrema and adjacent medulla is considered.", "contents": "Natriuresis following fourth ventricle perfusion with high-sodium artificial CSF. Perfusion of the fourth cerebral ventricle with high-sodium artificial cerebrospinal fluid was found to result in an increase in urinary sodium excretion in anesthetized cats. The natriuresis was accompanied by an increase in blood pressure and glomerular filtration rate. However, in animals with the changes in blood pressure and glomerular filtration rate prevented by alpha adrenergic blockade (phenoxybenzamine), the increase in urinary sodium excretion persisted. the data suggest the presence of a neural mechanism in the vicinity of the fourth ventricle sensitive to cerebrospinal fluid sodium levels and capable of affecting urinary sodium excretion independent of changes in blood pressure or glomerular filtration rate. The possible role of the area postrema and adjacent medulla is considered."}
{"id": "PMID:238726", "title": "Catecholamine binding to plasma membrane enriched fractions of heart 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 O degrees C. Binding was antagonized by the unlabeled beta-agonists, isopropylnorepinephrine, epinephrine, and norepinephrine but all were equipotent. A variety of catechol compounds were as effective antagonists of binding as the catecholamines. The beta-adrenergic antagonists propranolol, pronethalol, and dichloroisoproterenol were not effective in inhibiting binding to either membrane preparation. D-Norepinephrine and L-norepinephrine were equi-effective in antagonizing binding of [3H]norephinephrine to skeletal muscle membranes. It was concluded that binding of labeled catecholamine to isolated tissue membranes using the micropore filtration technique does not represent interaction with the specific beta-adrenergic receptor, but more likely reflects a less specific binding of compounds having one or more hydroxyl groups on a ring.", "contents": "Catecholamine binding to plasma membrane enriched fractions of heart 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 O degrees C. Binding was antagonized by the unlabeled beta-agonists, isopropylnorepinephrine, epinephrine, and norepinephrine but all were equipotent. A variety of catechol compounds were as effective antagonists of binding as the catecholamines. The beta-adrenergic antagonists propranolol, pronethalol, and dichloroisoproterenol were not effective in inhibiting binding to either membrane preparation. D-Norepinephrine and L-norepinephrine were equi-effective in antagonizing binding of [3H]norephinephrine to skeletal muscle membranes. It was concluded that binding of labeled catecholamine to isolated tissue membranes using the micropore filtration technique does not represent interaction with the specific beta-adrenergic receptor, but more likely reflects a less specific binding of compounds having one or more hydroxyl groups on a ring."}
{"id": "PMID:238727", "title": "Oxygen and effective vasular compliance in acute heart failure.", "content": "The effect of hypoxemia on total vascular compliance was studied in anesthetized dogs using a venous bypass technique. Cardiac output was kept constant with an extracorporeal pump and respiration controlled to maintain normocapnia. When nitrogen was added to the respired gas to produce an arterial PO2 approximately 45 mm Hg, total vascular compliance was rapidly and significantly reduced to 0.93 ml (mm Hg)(-1) kg(-1) with incomplete recovery to baseline values of 1.30 plus or minus 0.06 ml (mm Hg)(-1) kg(-1) during subsequent ventilation with 100% oxygen. Acute heart failure was induced by gradual aortic constriction. Ventilation with 100% oxygen failed to prevent a gradual reduction in total vascular compliance to 0.86 ml (mm Hg)(-1) kg(-1) from a baseline value of 1.23 plus or minus 0.06 ml (mm Hg)(-1) kg(-1). Ventilation with 100% oxygen following the reduction in vascular compliance during acute heart failure also failed to significantly alter this parameter. Thus, improvement of arterial oxygen tension in patients with acute heart failure would be beneficial in providing greater oxygen delivery to the tissues without abolishing a compensatory mechanism of reduced vascular compliance which attempts to maintain a cardiac filling gradient of pressure.", "contents": "Oxygen and effective vasular compliance in acute heart failure. The effect of hypoxemia on total vascular compliance was studied in anesthetized dogs using a venous bypass technique. Cardiac output was kept constant with an extracorporeal pump and respiration controlled to maintain normocapnia. When nitrogen was added to the respired gas to produce an arterial PO2 approximately 45 mm Hg, total vascular compliance was rapidly and significantly reduced to 0.93 ml (mm Hg)(-1) kg(-1) with incomplete recovery to baseline values of 1.30 plus or minus 0.06 ml (mm Hg)(-1) kg(-1) during subsequent ventilation with 100% oxygen. Acute heart failure was induced by gradual aortic constriction. Ventilation with 100% oxygen failed to prevent a gradual reduction in total vascular compliance to 0.86 ml (mm Hg)(-1) kg(-1) from a baseline value of 1.23 plus or minus 0.06 ml (mm Hg)(-1) kg(-1). Ventilation with 100% oxygen following the reduction in vascular compliance during acute heart failure also failed to significantly alter this parameter. Thus, improvement of arterial oxygen tension in patients with acute heart failure would be beneficial in providing greater oxygen delivery to the tissues without abolishing a compensatory mechanism of reduced vascular compliance which attempts to maintain a cardiac filling gradient of pressure."}
{"id": "PMID:238728", "title": "The microbial colonization of some woods of small dimensions buried in soil.", "content": "Several species of wood veneer, including some in a green undried state, were buried in various soils, and at intervals the colonists were isolated and identified. In addition, veneers were deteriorated for different periods of time, sterilized, and then reburied in the same soil. Isolates were obtained before sterilization and compared with those found afterwards. In each case the colonization involved a small number of microfungi and, because similar species were repeatedly isolated, an absence of succession under laboratory conditions was indicated. Deteriorating cubes of weed were periodically assayed for their glucose content, pH of exudates, and the release of microbial cellulase and amylase. A lack of any consistent change in colonist activity, with respect to these factors, again indicated an absence of stages during decay. The colonization pattern was contrasted with successions described in previous studies and the simplest explanation was given for the differences found.", "contents": "The microbial colonization of some woods of small dimensions buried in soil. Several species of wood veneer, including some in a green undried state, were buried in various soils, and at intervals the colonists were isolated and identified. In addition, veneers were deteriorated for different periods of time, sterilized, and then reburied in the same soil. Isolates were obtained before sterilization and compared with those found afterwards. In each case the colonization involved a small number of microfungi and, because similar species were repeatedly isolated, an absence of succession under laboratory conditions was indicated. Deteriorating cubes of weed were periodically assayed for their glucose content, pH of exudates, and the release of microbial cellulase and amylase. A lack of any consistent change in colonist activity, with respect to these factors, again indicated an absence of stages during decay. The colonization pattern was contrasted with successions described in previous studies and the simplest explanation was given for the differences found."}
{"id": "PMID:238729", "title": "A numerical taxonomic study of the strains of three types of Corynebacterium renale.", "content": "Numerical analysis has been carried out on 100 features of 55 strains of Corynebacterium renale. Three phena were formed, which respectively corresponded to three immunological types of C. renale.", "contents": "A numerical taxonomic study of the strains of three types of Corynebacterium renale. Numerical analysis has been carried out on 100 features of 55 strains of Corynebacterium renale. Three phena were formed, which respectively corresponded to three immunological types of C. renale."}
{"id": "PMID:238730", "title": "[The effect of pyridoxal phosphate on the tryptophanases of five species of Enterobacteriaceae].", "content": "Escherichia coli B and E. aurescens, Shigella alkalescens, and Proteus vulgaris et P. morganii tryptophanases (TPases) were studied for the spectral forms of the enzyme. The pH effect on the absorption spectrum and on the enzyme specific activity revealed that the coli group TPases are identical with but differ from Proteus TPases which differ themselves. The coli group TPases attach 4 mol of pyridoxal phosphate (PLP)/mol of enzyme, independently of the pH in the presence of K(plus) ions, and 9 mol of PLP/mol of enzyme must be reduced to achieve complete inactivation. The Proteus TPases attach 4 mol of PLP/mol of enzyme at PH 6.8, and 3 mol of PLP/mol of enzyme at pH 7.8 in K(plus) buffer. In P. morganii, 7 mol of PLP/mol of enzyme must be reduced to inactivate the enzyme, whereas P. vulgaris TPase cannot be completely inactivated by this method. These five TPases attach only 3 mol of PLP/mol of enzyme in a Na(plus) buffer, independently of the pH.", "contents": "[The effect of pyridoxal phosphate on the tryptophanases of five species of Enterobacteriaceae]. Escherichia coli B and E. aurescens, Shigella alkalescens, and Proteus vulgaris et P. morganii tryptophanases (TPases) were studied for the spectral forms of the enzyme. The pH effect on the absorption spectrum and on the enzyme specific activity revealed that the coli group TPases are identical with but differ from Proteus TPases which differ themselves. The coli group TPases attach 4 mol of pyridoxal phosphate (PLP)/mol of enzyme, independently of the pH in the presence of K(plus) ions, and 9 mol of PLP/mol of enzyme must be reduced to achieve complete inactivation. The Proteus TPases attach 4 mol of PLP/mol of enzyme at PH 6.8, and 3 mol of PLP/mol of enzyme at pH 7.8 in K(plus) buffer. In P. morganii, 7 mol of PLP/mol of enzyme must be reduced to inactivate the enzyme, whereas P. vulgaris TPase cannot be completely inactivated by this method. These five TPases attach only 3 mol of PLP/mol of enzyme in a Na(plus) buffer, independently of the pH."}
{"id": "PMID:238731", "title": "Enzymes of ammonia assimilation in Rhizobium leguminosarum bacteroids.", "content": "The activities of the following enzymes were studied in connection with dinitrogen fixation in pea bacteroids: glutamine synthetase(L-glutamate: ammonia ligase (ADP-forming)(EC 6.3.1.2)(GS); glutamate dehydrogenase (NADP+)(L-glutamate: NADP+ oxidoreductase (deaminating)(EC 1.4.1.4)(GDH); glutamate synthase (L-glutamine: 2-exeglutarate aminotransferase (NADPH-oxidizing))(EC 2.6.1.53)(GOGAT). GS activity was high throughout the growth of the plant and GOGAT activity was always low. It is unlikely that GDH or the GS-GOGAT pathway can account for the incorporation of ammonia from dinitrogen fixation in the pea bacteroid,", "contents": "Enzymes of ammonia assimilation in Rhizobium leguminosarum bacteroids. The activities of the following enzymes were studied in connection with dinitrogen fixation in pea bacteroids: glutamine synthetase(L-glutamate: ammonia ligase (ADP-forming)(EC 6.3.1.2)(GS); glutamate dehydrogenase (NADP+)(L-glutamate: NADP+ oxidoreductase (deaminating)(EC 1.4.1.4)(GDH); glutamate synthase (L-glutamine: 2-exeglutarate aminotransferase (NADPH-oxidizing))(EC 2.6.1.53)(GOGAT). GS activity was high throughout the growth of the plant and GOGAT activity was always low. It is unlikely that GDH or the GS-GOGAT pathway can account for the incorporation of ammonia from dinitrogen fixation in the pea bacteroid,"}
{"id": "PMID:238732", "title": "The isolation and characterization of a temperate phage, Y46/(E2), from Erwinia herbicola Y40.", "content": "A temperate phage was induced from exponential phase cells of Erwinia herbicola Y46 by treatment with mitomycin C. The phage was purified by single plaque isolation, and produced in bulk by successive cultivation in young cultures of E. herbicola Y 178. Phages were concentrated from culture filtrates by rate zonal centrifugation and resuspension in 0.02 M Tris buffer, pH 7.2, twice, yielding suspensions of about 5 times 10(11) PFU/ml. Purification was achieved by centrifugation in buffered sucrose solutions. The band at the 30/40% sucrose interface yielded intact particles having regular hexagonal heads and lonb contractile tails, with base plates. Fibers were not seen. The mean dimensions were head, 51 nm; neck length, 11 nm; overall tail length, extended, 98 nm and contracted, 75 nm; diameter of tail sheath, 24 nm. The phage was stable from pH 4.0 to 11.0, but unstable at pH 3.0, the response being independent of the suspending medium used. At pH 3.0, a survival curve having biphasic appearance was observed, which was not due to a mixed population of phages. Stability to heat was good up to 45 degrees C, above which a logarithmic decline with temperature increase occurred. The average inactivation rate constant at 50 degrees C and pH 6.8 was 0.15 min-1. Adsorption to E. herbicola Y 178 cells exhibited first-order kinetics, the adsorption rate constant being 2.5 times 10(-10) ml/min. One-step growth-curve experiments indicated a burst size of 35-40, and a minimum latent period of 80 min. Probit analysis gave a mean latent period of 140 min (SD 25). The phage caused lysis of only E. herbicola strains Y178 and Y186.", "contents": "The isolation and characterization of a temperate phage, Y46/(E2), from Erwinia herbicola Y40. A temperate phage was induced from exponential phase cells of Erwinia herbicola Y46 by treatment with mitomycin C. The phage was purified by single plaque isolation, and produced in bulk by successive cultivation in young cultures of E. herbicola Y 178. Phages were concentrated from culture filtrates by rate zonal centrifugation and resuspension in 0.02 M Tris buffer, pH 7.2, twice, yielding suspensions of about 5 times 10(11) PFU/ml. Purification was achieved by centrifugation in buffered sucrose solutions. The band at the 30/40% sucrose interface yielded intact particles having regular hexagonal heads and lonb contractile tails, with base plates. Fibers were not seen. The mean dimensions were head, 51 nm; neck length, 11 nm; overall tail length, extended, 98 nm and contracted, 75 nm; diameter of tail sheath, 24 nm. The phage was stable from pH 4.0 to 11.0, but unstable at pH 3.0, the response being independent of the suspending medium used. At pH 3.0, a survival curve having biphasic appearance was observed, which was not due to a mixed population of phages. Stability to heat was good up to 45 degrees C, above which a logarithmic decline with temperature increase occurred. The average inactivation rate constant at 50 degrees C and pH 6.8 was 0.15 min-1. Adsorption to E. herbicola Y 178 cells exhibited first-order kinetics, the adsorption rate constant being 2.5 times 10(-10) ml/min. One-step growth-curve experiments indicated a burst size of 35-40, and a minimum latent period of 80 min. Probit analysis gave a mean latent period of 140 min (SD 25). The phage caused lysis of only E. herbicola strains Y178 and Y186."}
{"id": "PMID:238733", "title": "The inhibition of bacterial growth by ochratoxin A.", "content": "A series of bacterial species was examined for their sensitivity to ochratoxin A. Only grampositive bacteria could be inhibited, generally at a pH lower than 7.0. Bacillus subtilis did not show any reduction of growth rates in presence of ochratoxin A, but had a prolonged lag phase. With Staphylococcus pyogenes var. aureus and Streptococcus faecalis, a prolonged lag phase and a reduction of the growth rate was observed. Most sensitive was Streptococcus faecalis in the exponential-growth phase. The inhibition could be diminished by changing the pH to neutral, or by addition of yeast extract, tetrahydrofolate, or MgSO4. With MgSO4 a complete abolition of the inhibitory effect was achieved, but not with CaCl2. During growth inhibition, protein and RNA synthesis were reduced simultaneously, but not DNA synthesis. Even with the very high concentration of 1 mg/ml, no lethal effect was observed.", "contents": "The inhibition of bacterial growth by ochratoxin A. A series of bacterial species was examined for their sensitivity to ochratoxin A. Only grampositive bacteria could be inhibited, generally at a pH lower than 7.0. Bacillus subtilis did not show any reduction of growth rates in presence of ochratoxin A, but had a prolonged lag phase. With Staphylococcus pyogenes var. aureus and Streptococcus faecalis, a prolonged lag phase and a reduction of the growth rate was observed. Most sensitive was Streptococcus faecalis in the exponential-growth phase. The inhibition could be diminished by changing the pH to neutral, or by addition of yeast extract, tetrahydrofolate, or MgSO4. With MgSO4 a complete abolition of the inhibitory effect was achieved, but not with CaCl2. During growth inhibition, protein and RNA synthesis were reduced simultaneously, but not DNA synthesis. Even with the very high concentration of 1 mg/ml, no lethal effect was observed."}
{"id": "PMID:238734", "title": "The dorsomedial hypothalamic nucleus in autonomic and neuroendocrine homeostasis.", "content": "Median eminence and ventromedial hypothalamus have in the past been the principal foci of research in neuroendocrine and neurovisceral control mechanisms. The present report provides an overview of work involving the dorsomedial hypothalamic nucleus (DMV). This structure is located dorsal to the ventromedial hypothalamic nucleus (VMN) to the plane of the dorsal premammillary nucleus. Fibers from the DMN pass with the periventricular system and the dorsal longitudinal fasciculus of Sch\u00fctz and have been traced to the midbrain tegmentum and reticular formation. Intrahypothalamic connections involve intensive networks between DMN, lateral hypothalamic nucleus (LHN) and VMN. Regarding neurotransmitters, recent studies indicate that the DMN receives noradrenergic innervation along two pathways, a dorsal and a ventral one. Monoamine-containing systems approach the DMN From the lateral hypothalamus and the bulk of these fibers are carried in the medium forebrain bundle from their cells of origin in the brain stem. Studies of the vascular supply indicate that both VMN and DMN receive their blood supply from the internal carotid artery...", "contents": "The dorsomedial hypothalamic nucleus in autonomic and neuroendocrine homeostasis. Median eminence and ventromedial hypothalamus have in the past been the principal foci of research in neuroendocrine and neurovisceral control mechanisms. The present report provides an overview of work involving the dorsomedial hypothalamic nucleus (DMV). This structure is located dorsal to the ventromedial hypothalamic nucleus (VMN) to the plane of the dorsal premammillary nucleus. Fibers from the DMN pass with the periventricular system and the dorsal longitudinal fasciculus of Sch\u00fctz and have been traced to the midbrain tegmentum and reticular formation. Intrahypothalamic connections involve intensive networks between DMN, lateral hypothalamic nucleus (LHN) and VMN. Regarding neurotransmitters, recent studies indicate that the DMN receives noradrenergic innervation along two pathways, a dorsal and a ventral one. Monoamine-containing systems approach the DMN From the lateral hypothalamus and the bulk of these fibers are carried in the medium forebrain bundle from their cells of origin in the brain stem. Studies of the vascular supply indicate that both VMN and DMN receive their blood supply from the internal carotid artery..."}
{"id": "PMID:238735", "title": "Observations on trace proteins in plasma of febrile patients by cationic disc electrophoresis in acrylamide gel at pH 3.8.", "content": "Cationic disc electrophoresis at pH 3.5 in 6 M urea-containing acrylamide gels permits analysis of plasma and other body fluids for the presence of trace proteins with pI greater than or equal 5 and M.W. less than 60,000. These charge and size characteristics would include rabbit and human granulocytic pyrogen, human monocytic pyrogen and, by inference, other similar candidate pyrogenic proteins. Semiquantitation of the trace protein content can be achieved by densitometric scanning of gels stained with Amido schwarz. Duplicate analyses were performed on plasma samples from 133 individuals: normal, 15; afebrile advanced cancer, 18; afebrile Hodgkin's disease, 30; febrile Hodgkin's disease, 33; other febrile lymphoma, 13; febrile advanced cancer without infection, 12; and pyogenic fever, 12. Plasma from most of the febrile patients, particularly from febrile Hodgkin's disease patients, contained trace proteins not detectable in the afebrile individuals studied. In patients with Hodgkin's disease the quantity of trace proteins present in plasma correlated well with overall severity of Hodgkin's pyrexia, but not with spontaneous hr to hr fluctuations in the fever. Marked reduction in plasma levels of the trace proteins occurred with response to antitumor therapy. Elevated plasma levels of these proteins can be induced by intratumoral inoculation of Bacillus Calmette-Gu\u00e9rin. They appear concomitant with the febrile response.", "contents": "Observations on trace proteins in plasma of febrile patients by cationic disc electrophoresis in acrylamide gel at pH 3.8. Cationic disc electrophoresis at pH 3.5 in 6 M urea-containing acrylamide gels permits analysis of plasma and other body fluids for the presence of trace proteins with pI greater than or equal 5 and M.W. less than 60,000. These charge and size characteristics would include rabbit and human granulocytic pyrogen, human monocytic pyrogen and, by inference, other similar candidate pyrogenic proteins. Semiquantitation of the trace protein content can be achieved by densitometric scanning of gels stained with Amido schwarz. Duplicate analyses were performed on plasma samples from 133 individuals: normal, 15; afebrile advanced cancer, 18; afebrile Hodgkin's disease, 30; febrile Hodgkin's disease, 33; other febrile lymphoma, 13; febrile advanced cancer without infection, 12; and pyogenic fever, 12. Plasma from most of the febrile patients, particularly from febrile Hodgkin's disease patients, contained trace proteins not detectable in the afebrile individuals studied. In patients with Hodgkin's disease the quantity of trace proteins present in plasma correlated well with overall severity of Hodgkin's pyrexia, but not with spontaneous hr to hr fluctuations in the fever. Marked reduction in plasma levels of the trace proteins occurred with response to antitumor therapy. Elevated plasma levels of these proteins can be induced by intratumoral inoculation of Bacillus Calmette-Gu\u00e9rin. They appear concomitant with the febrile response."}
{"id": "PMID:238736", "title": "Use of cationic disc electrophoresis near neutral pH in the evaluation of trace proteins in human plasma.", "content": "Cationic discontinuous electrophoresis can be carried out at pH 6.0 With excellent resolution in urea-containing acrylamide gels with potassium as the leading ion, 3-picoline as the trailing ion, and cacodylic acid as the buffer. This analytic technique has consistently demonstrated trace protein abnormalities in plasma or serum from febrile patients. It has made possible the detection of three protein bands that were obscured in similar electrophoretic assays at pH 3.8 A rough parallelism is found in the plasma (or serum) content of the five protein bands regardless of the apparent clinical cause of the febrile state.", "contents": "Use of cationic disc electrophoresis near neutral pH in the evaluation of trace proteins in human plasma. Cationic discontinuous electrophoresis can be carried out at pH 6.0 With excellent resolution in urea-containing acrylamide gels with potassium as the leading ion, 3-picoline as the trailing ion, and cacodylic acid as the buffer. This analytic technique has consistently demonstrated trace protein abnormalities in plasma or serum from febrile patients. It has made possible the detection of three protein bands that were obscured in similar electrophoretic assays at pH 3.8 A rough parallelism is found in the plasma (or serum) content of the five protein bands regardless of the apparent clinical cause of the febrile state."}
{"id": "PMID:238737", "title": "Multiple molecular forms of glucose-6-phosphate dehydrogenase in normal, preneoplastic, and neoplastic mammary tissues of mice.", "content": "Multiple molecular forms of glucose-6-phosphate dehydrogenase (G6PD) in normal, preneoplastic, and neoplastic mammary tissues were separated by polyacrylamide gel electrophoresis and identified by specific straining for enzyme activity. Mammary tissue from lactating BALB/c mice showed considerable amounts (up to 50%) of a slower-migrating G6PD species, G6PD-III, which was essentially absent from glands of pregnant mice, preneoplastic nodules, and mammary carcinomas. All tissues possessed a faster-migrating species, G6PD-II, which accounted for up to 85% of the total G6PD in the glands of pregnant mice. A third species, G6PD-I, migrating more rapidly than G6PD-II, was found in both abnormal tissues (preneoplastic and neoplastic) and accounted for up to 35% of the total enzymatic activity. G6PD-I was present in moderate amounts (less than 15%) in glands from pregnant mice and was essentially absent from the lactating gland (approximately 5%). The addition of dithiothreitol did not alter the measurable G6PD activity but did increase the relative activity of G6PD-II or G6PD-I, as judged by the intensity of the bands on the gels. Mild oxidation (stirring overnight at 4 degrees in air) resulted in a loss of G6PD activity, but preparations had greater amounts of G6PD-III; presence of dithiothreitol during aeration partially prevented loss of G6PD activity and largely prvented the appearance of G6PD-III. Molecular-weight estimations with preparations from lactating mice yielded a value of 118,000 for G6PD-II and 260,000 for G6PD-III, suggesting a monomer and dimer, respectively. The addition of nicotinamide adenine dinucleotide phosphate stabilized G6PD activity by preventing heat inactivation at 47 degrees; nicotinamide adenine dinucleotide phosphate did not alter the pattern of species present. The data from heat inactivation studies suggest that G6PD-III (dimer) was the more stable species. The addition of nicotinamide adenine dinucleotide phosphate to samples after oxidation in the absence of dithiothreitol (about 70% loss of activity) resulted in no change in patterns and in recovery of full G6PD activity during heating at 47 degrees. A potential relationship between glutathione reductase activity and the pattern of G6PD species observed in the various tissues is noted.", "contents": "Multiple molecular forms of glucose-6-phosphate dehydrogenase in normal, preneoplastic, and neoplastic mammary tissues of mice. Multiple molecular forms of glucose-6-phosphate dehydrogenase (G6PD) in normal, preneoplastic, and neoplastic mammary tissues were separated by polyacrylamide gel electrophoresis and identified by specific straining for enzyme activity. Mammary tissue from lactating BALB/c mice showed considerable amounts (up to 50%) of a slower-migrating G6PD species, G6PD-III, which was essentially absent from glands of pregnant mice, preneoplastic nodules, and mammary carcinomas. All tissues possessed a faster-migrating species, G6PD-II, which accounted for up to 85% of the total G6PD in the glands of pregnant mice. A third species, G6PD-I, migrating more rapidly than G6PD-II, was found in both abnormal tissues (preneoplastic and neoplastic) and accounted for up to 35% of the total enzymatic activity. G6PD-I was present in moderate amounts (less than 15%) in glands from pregnant mice and was essentially absent from the lactating gland (approximately 5%). The addition of dithiothreitol did not alter the measurable G6PD activity but did increase the relative activity of G6PD-II or G6PD-I, as judged by the intensity of the bands on the gels. Mild oxidation (stirring overnight at 4 degrees in air) resulted in a loss of G6PD activity, but preparations had greater amounts of G6PD-III; presence of dithiothreitol during aeration partially prevented loss of G6PD activity and largely prvented the appearance of G6PD-III. Molecular-weight estimations with preparations from lactating mice yielded a value of 118,000 for G6PD-II and 260,000 for G6PD-III, suggesting a monomer and dimer, respectively. The addition of nicotinamide adenine dinucleotide phosphate stabilized G6PD activity by preventing heat inactivation at 47 degrees; nicotinamide adenine dinucleotide phosphate did not alter the pattern of species present. The data from heat inactivation studies suggest that G6PD-III (dimer) was the more stable species. The addition of nicotinamide adenine dinucleotide phosphate to samples after oxidation in the absence of dithiothreitol (about 70% loss of activity) resulted in no change in patterns and in recovery of full G6PD activity during heating at 47 degrees. A potential relationship between glutathione reductase activity and the pattern of G6PD species observed in the various tissues is noted."}
{"id": "PMID:238738", "title": "Binding of [3H]benzo(a)pyrene to natural and synthetic nucleic acids in a subcellular microsomal system.", "content": "Several carcinogens are bound covalently to cellular nucleic acids. This is also the case with polycyclic hydrocarbon carcinogens, but their precise mechanism of in vivo activation to reactive forms and the structure(s) of the nucleic acid adducts are not known. This study demonstrates that in the presence of rat liver microsomes and reduced nicotinamide adenine dinucleotide phosphate there is covalent attachment of tritiated benzo(a)pyrene (BP) to transfer RNA, DNA, certain synthetic polyribonucleotides, and an RNA species endogenous to the microsomal fraction. Evidence has been obtained that the binding occurs mainly to guanine and, to a lesser extent, adenine residues and is not simple an artifact of tritium exchange. The microsomal-mediated binding of [3H]BP to nucleic acids requires reduced nicotinamide adenine dinucleotide phosphate and in inhibited by 7,8-benzoflavone, glutathione, and magnesium. It is enhanced somewhat by the addition of styrene oxide, cyclohexene oxide, and trichloropropylene oxide. These results provide the first evidence that: (a) the microsome-mediated binding of [3H]BP to nucleic acids is not just due to tritium exchange; (b) a derivative of the hydrocarbon is covalently bound to the nucleic acid, and not simply intercalated; (c) there is a preferential binding to guanine residues; and (d) in addition to binding to exogenous nucleic acids, [3H]BP is bound to an RNA species present in the microsomes. Our data are consistent with but do not prove that nucleic acid binding of this polycyclic hydrocarbon proceeds via an epoxide intermediate.", "contents": "Binding of [3H]benzo(a)pyrene to natural and synthetic nucleic acids in a subcellular microsomal system. Several carcinogens are bound covalently to cellular nucleic acids. This is also the case with polycyclic hydrocarbon carcinogens, but their precise mechanism of in vivo activation to reactive forms and the structure(s) of the nucleic acid adducts are not known. This study demonstrates that in the presence of rat liver microsomes and reduced nicotinamide adenine dinucleotide phosphate there is covalent attachment of tritiated benzo(a)pyrene (BP) to transfer RNA, DNA, certain synthetic polyribonucleotides, and an RNA species endogenous to the microsomal fraction. Evidence has been obtained that the binding occurs mainly to guanine and, to a lesser extent, adenine residues and is not simple an artifact of tritium exchange. The microsomal-mediated binding of [3H]BP to nucleic acids requires reduced nicotinamide adenine dinucleotide phosphate and in inhibited by 7,8-benzoflavone, glutathione, and magnesium. It is enhanced somewhat by the addition of styrene oxide, cyclohexene oxide, and trichloropropylene oxide. These results provide the first evidence that: (a) the microsome-mediated binding of [3H]BP to nucleic acids is not just due to tritium exchange; (b) a derivative of the hydrocarbon is covalently bound to the nucleic acid, and not simply intercalated; (c) there is a preferential binding to guanine residues; and (d) in addition to binding to exogenous nucleic acids, [3H]BP is bound to an RNA species present in the microsomes. Our data are consistent with but do not prove that nucleic acid binding of this polycyclic hydrocarbon proceeds via an epoxide intermediate."}
{"id": "PMID:238743", "title": "Staocysts of hydromedusae.", "content": "The statocysts of Leptomedusae are formed as a depression in the velum. They are lined on the inside towards the distal part of the velum by thin epithelium and towards the proximal part by ciliated sensory cells. Lithocytes are present in the centre. The concretion contains calcium sulphate and in some cases, calcium phosphate is also present in addition to some membranous material. The statocysts of Narcomedusae arise from the exumbrellar nerve ring as free sensory clubs. They have a proximal basal cushion of sensory cells from the centre of which arises a sensory club (Aegina) or a sensory papilla carrying a sensory club (Solmissus). The sensory club has an axial strand of endodermal cells covered by ciliated sensory cells. Some of the endodermal cells have a concretion. While the statocysts of Leptomedusae are totally ectodermal, those of Narcomedusae are ecto-endodermal in origin. The sensory cilia of Leptomedusae, especially those present on the sensory cells adjacent to the lithocyte, run close and parallel to the lithocyte membrane. In Narcomedusae the sensory cilia of the basal cusion and sensory papilla are tall and strong. Ciliary rootlets are missing in the sensory cilia of Leptomedusae and in the sensory club of Narcomedusae but they are strongly developed in the cilia of basal cusion and sensory papilla. The cilia have 9+2 filament content. A ring of stereocilia surrounds the kinocilium of the sensory club cells. Mechanism of statocyst function is discussed.", "contents": "Staocysts of hydromedusae. The statocysts of Leptomedusae are formed as a depression in the velum. They are lined on the inside towards the distal part of the velum by thin epithelium and towards the proximal part by ciliated sensory cells. Lithocytes are present in the centre. The concretion contains calcium sulphate and in some cases, calcium phosphate is also present in addition to some membranous material. The statocysts of Narcomedusae arise from the exumbrellar nerve ring as free sensory clubs. They have a proximal basal cushion of sensory cells from the centre of which arises a sensory club (Aegina) or a sensory papilla carrying a sensory club (Solmissus). The sensory club has an axial strand of endodermal cells covered by ciliated sensory cells. Some of the endodermal cells have a concretion. While the statocysts of Leptomedusae are totally ectodermal, those of Narcomedusae are ecto-endodermal in origin. The sensory cilia of Leptomedusae, especially those present on the sensory cells adjacent to the lithocyte, run close and parallel to the lithocyte membrane. In Narcomedusae the sensory cilia of the basal cusion and sensory papilla are tall and strong. Ciliary rootlets are missing in the sensory cilia of Leptomedusae and in the sensory club of Narcomedusae but they are strongly developed in the cilia of basal cusion and sensory papilla. The cilia have 9+2 filament content. A ring of stereocilia surrounds the kinocilium of the sensory club cells. Mechanism of statocyst function is discussed."}
{"id": "PMID:238744", "title": "Ultrastructure of nematocytes and one-celled tentacles of the freshwater coelenterate, Calpasoma dactyloptera.", "content": "Calpasoma dactyloptera, a tentacled form of minute, freshwater coelenterate, has been investigated by light and electron microscopy and time-lapse cinematography. Each tentacle consists of a protrusion from a single ectodermal epithelial cell termed a tentaculocyte. Thus, unlike most coelenterate tentacles, neither mesoglea nor endoderm is present in the tentacle. Large numbers of nematocytes are present, however. When the nematocytes are poised, they sit within tentaculocyte vesicles which represent invaginations of the plasma membrane. A cnidocil protrudes into the external medium. The bottom of each nematocyte is elongated as a stalk which extends to the tentacle base, coursing through tubular membrane lined channels within the tentaculocyte. A network of fibers and microtubules, originating in the cnidocil, extends to the base of the nematocyte stalk.", "contents": "Ultrastructure of nematocytes and one-celled tentacles of the freshwater coelenterate, Calpasoma dactyloptera. Calpasoma dactyloptera, a tentacled form of minute, freshwater coelenterate, has been investigated by light and electron microscopy and time-lapse cinematography. Each tentacle consists of a protrusion from a single ectodermal epithelial cell termed a tentaculocyte. Thus, unlike most coelenterate tentacles, neither mesoglea nor endoderm is present in the tentacle. Large numbers of nematocytes are present, however. When the nematocytes are poised, they sit within tentaculocyte vesicles which represent invaginations of the plasma membrane. A cnidocil protrudes into the external medium. The bottom of each nematocyte is elongated as a stalk which extends to the tentacle base, coursing through tubular membrane lined channels within the tentaculocyte. A network of fibers and microtubules, originating in the cnidocil, extends to the base of the nematocyte stalk."}
{"id": "PMID:238745", "title": "Aminergic nuclei in the hypothalamus of the roach Leuciscus rutilus.", "content": "In the hypothalamus of the roach (Leuciscus rutilus) green and yellow fluorescent cells were found in the nucleus recessus lateralis (NRL) and the nucleus recessus posterioris (NRP) and green fluorescent cells in the nucleus recessus preopticus (NRPO). The green fluorescence indicates the presence of noradrenaline or dopamine and the yellow one the presence of 5-hydroxytryptamine. The cells of the NRL and NRP contained electron dense granules averaging 70 nm in diameter. The NRL is divided into two parts. These and the NRP are connected by large fluorescent tracts. The NRL and NRP send axons towards the nucleus lateralis tuberis (NLT) and the NRPO sends axons towards the nucleus preopticus (NPO). It could not be established whether the aminergic nuclei described are the origin of the fluorescent fibers in the hypophysis of the roach.", "contents": "Aminergic nuclei in the hypothalamus of the roach Leuciscus rutilus. In the hypothalamus of the roach (Leuciscus rutilus) green and yellow fluorescent cells were found in the nucleus recessus lateralis (NRL) and the nucleus recessus posterioris (NRP) and green fluorescent cells in the nucleus recessus preopticus (NRPO). The green fluorescence indicates the presence of noradrenaline or dopamine and the yellow one the presence of 5-hydroxytryptamine. The cells of the NRL and NRP contained electron dense granules averaging 70 nm in diameter. The NRL is divided into two parts. These and the NRP are connected by large fluorescent tracts. The NRL and NRP send axons towards the nucleus lateralis tuberis (NLT) and the NRPO sends axons towards the nucleus preopticus (NPO). It could not be established whether the aminergic nuclei described are the origin of the fluorescent fibers in the hypophysis of the roach."}
{"id": "PMID:238746", "title": "Testicular lipids in mice with testicular feminization.", "content": "Morphological, histochemical and biochemical studies of the testis of mice with testicular feminization (tfm/y) reveal a large accumulation of lipids in Leydig cells and in Sertoli cells. In Leydig cells of tfm/y mice, lipid droplets do not exhibit the special relationship with smooth endoplasmic reticulum that exists in normal adult Leydig cells. Compared to the surgically-cryptorchid control, the tfm/y testis contains more lipid in Leydig cells but less in Sertoli cells. There are also quantitative differences in testicular lipids in tmf/y and normal testes but no significant differences were noted between tfm/y and surgically-cryptorchid testes. The testes of both the genetically defective and surgically-cryptochid animals contain increased amounts of total lipids and phospholipids, and of free and esterified cholesterols. Exogenous testosterone has no effect on lipids or other characteristics of these cells. The present results suggest that the increased lipids in tfm/y mice result from a genetic disorder that asserts itself (1) in Leydig cells where it is associated with, and is probably a result of, impaired lipid metabolism and steroidogenesis, and (2) in Sertoli cells where it is perhaps attributable to arrested spermatogenesis and impaired steroidogenesis.", "contents": "Testicular lipids in mice with testicular feminization. Morphological, histochemical and biochemical studies of the testis of mice with testicular feminization (tfm/y) reveal a large accumulation of lipids in Leydig cells and in Sertoli cells. In Leydig cells of tfm/y mice, lipid droplets do not exhibit the special relationship with smooth endoplasmic reticulum that exists in normal adult Leydig cells. Compared to the surgically-cryptorchid control, the tfm/y testis contains more lipid in Leydig cells but less in Sertoli cells. There are also quantitative differences in testicular lipids in tmf/y and normal testes but no significant differences were noted between tfm/y and surgically-cryptorchid testes. The testes of both the genetically defective and surgically-cryptochid animals contain increased amounts of total lipids and phospholipids, and of free and esterified cholesterols. Exogenous testosterone has no effect on lipids or other characteristics of these cells. The present results suggest that the increased lipids in tfm/y mice result from a genetic disorder that asserts itself (1) in Leydig cells where it is associated with, and is probably a result of, impaired lipid metabolism and steroidogenesis, and (2) in Sertoli cells where it is perhaps attributable to arrested spermatogenesis and impaired steroidogenesis."}
{"id": "PMID:238748", "title": "[Properties of the laccase of Botrytis cinerea].", "content": "Laccase from Botrytis cinerea, secreted by the fungus into the grape berry, is responsible for the oxidation phynomena in musts and wines (oxidasic casse). From a fungus culture, the enzyme was extracted for a study of its properties: specificity; influence of inhibitors, pH and temperature; The results confirm that the enzyme from Botrytis cinerea belongs to the laccase family, though it has some characteristic differences from the other laccases previously described.", "contents": "[Properties of the laccase of Botrytis cinerea]. Laccase from Botrytis cinerea, secreted by the fungus into the grape berry, is responsible for the oxidation phynomena in musts and wines (oxidasic casse). From a fungus culture, the enzyme was extracted for a study of its properties: specificity; influence of inhibitors, pH and temperature; The results confirm that the enzyme from Botrytis cinerea belongs to the laccase family, though it has some characteristic differences from the other laccases previously described."}
{"id": "PMID:238749", "title": "[Peroxidase activity of neutrophil granules in two cases of congenital myeloperoxidase deficiency].", "content": "The neutrophils and monocytes of two patients with hereditary myeloperoxidase deficiency lacked myeloperoxidase activity as determined by light and electron microscopic cytochemical staining. Using Graham-Karnovsky media, azurophils of neutrophils were devoid of peroxidase whereas all eosinophilic and basophilic granules exhibited normal peroxidase activity. After incubation in alkaline diaminobenzidine media which stains the catalase of microperoxisomes, some small granules were seen to be strongly stained in both immature and mature neutrophils. These small granules were distinct from all other neutrophilic granules which lacked a positive reaction. Only, in the presence of cyanide or aminotriazole, peroxidatic activity was also detected in some ellipsoid azurophils. This observation suggests that these substances activated an oxidase whose nature is discussed.", "contents": "[Peroxidase activity of neutrophil granules in two cases of congenital myeloperoxidase deficiency]. The neutrophils and monocytes of two patients with hereditary myeloperoxidase deficiency lacked myeloperoxidase activity as determined by light and electron microscopic cytochemical staining. Using Graham-Karnovsky media, azurophils of neutrophils were devoid of peroxidase whereas all eosinophilic and basophilic granules exhibited normal peroxidase activity. After incubation in alkaline diaminobenzidine media which stains the catalase of microperoxisomes, some small granules were seen to be strongly stained in both immature and mature neutrophils. These small granules were distinct from all other neutrophilic granules which lacked a positive reaction. Only, in the presence of cyanide or aminotriazole, peroxidatic activity was also detected in some ellipsoid azurophils. This observation suggests that these substances activated an oxidase whose nature is discussed."}
{"id": "PMID:238750", "title": "[Increase in the hypothalamic tyrosine hydroxylase activity after lesion of the catecholaminergic neurons of the rat pontine tegmentum].", "content": "Hypothalamic tyrosine hydroxylase activity is increased 6 and 18 h after bilateral lesioning of the Locus Coerulues, in the Rat.  An adrenocortical hypertrophy was observed previously, under the same experimental conditions.  The neurochemical and neuroendocrinological implications of theses results are discussed.", "contents": "[Increase in the hypothalamic tyrosine hydroxylase activity after lesion of the catecholaminergic neurons of the rat pontine tegmentum]. Hypothalamic tyrosine hydroxylase activity is increased 6 and 18 h after bilateral lesioning of the Locus Coerulues, in the Rat.  An adrenocortical hypertrophy was observed previously, under the same experimental conditions.  The neurochemical and neuroendocrinological implications of theses results are discussed."}
{"id": "PMID:238751", "title": "[Acid-base homeostasis and the thyro-parathyroid glands].", "content": "Chronic metabolic acidosis entails hyperparathyroidism and osteopathy. In order to elucidate the role of the thyroparathyroids in this bone lesion production the effects of acidic diet for 7 weeks were studied in parathyroidectomized (PTX), thyroparathyroidectomized (TPTX) and shamoperated (Sh-O) growing rats. In all animals urinary excretion of calcium, phosphate, ammonium and titrable acidity was similarly increased. The rise in hydroxyproline excretion and urinary 85-sr (that was injected previous to acidic feeding) was more marked in PTX and TPTX rats. Moreover, in these animals the serum calcium level was increased, the blood pH was decreased. According to these data, an acidic diet intake that is not sufficient to elicit a fall in blood pH of normal young rats can induce severe acidosis in chronically parathyroidectomized or thyroparathyroidectomized animals; moreover the bone resorption appears more marked. It is concluded that parathyroids are involved in the extra-cellular fluid defense mechanism against acidosis by a no bone resorptive mechanism. We hypothesize that the parathyroids permit the necessary and adequate supply of bicarbonates by the bone to maintain blood pH homeostasis.", "contents": "[Acid-base homeostasis and the thyro-parathyroid glands]. Chronic metabolic acidosis entails hyperparathyroidism and osteopathy. In order to elucidate the role of the thyroparathyroids in this bone lesion production the effects of acidic diet for 7 weeks were studied in parathyroidectomized (PTX), thyroparathyroidectomized (TPTX) and shamoperated (Sh-O) growing rats. In all animals urinary excretion of calcium, phosphate, ammonium and titrable acidity was similarly increased. The rise in hydroxyproline excretion and urinary 85-sr (that was injected previous to acidic feeding) was more marked in PTX and TPTX rats. Moreover, in these animals the serum calcium level was increased, the blood pH was decreased. According to these data, an acidic diet intake that is not sufficient to elicit a fall in blood pH of normal young rats can induce severe acidosis in chronically parathyroidectomized or thyroparathyroidectomized animals; moreover the bone resorption appears more marked. It is concluded that parathyroids are involved in the extra-cellular fluid defense mechanism against acidosis by a no bone resorptive mechanism. We hypothesize that the parathyroids permit the necessary and adequate supply of bicarbonates by the bone to maintain blood pH homeostasis."}
{"id": "PMID:238752", "title": "[Alpha-mannosidase activity of different human biological fluids].", "content": "Two distinct alpha-mannosidases have been found in biological fluids by investigating the effect of pH on activity, the effect of Co2+ and Zn2+ and by determining the Michaelis constant. The two enzymes are designated as S, predominating in serum (optimum pH about 5.6) and U, predominating in urine (optimum pH about 4.2). In cerebro-spinal fluid, the amount of alpha-mannosidase S is almost the same as that of alpha-mannosidase U. Alpha-mannosidase S activity in sera is significantly higher in children than in adults.", "contents": "[Alpha-mannosidase activity of different human biological fluids]. Two distinct alpha-mannosidases have been found in biological fluids by investigating the effect of pH on activity, the effect of Co2+ and Zn2+ and by determining the Michaelis constant. The two enzymes are designated as S, predominating in serum (optimum pH about 5.6) and U, predominating in urine (optimum pH about 4.2). In cerebro-spinal fluid, the amount of alpha-mannosidase S is almost the same as that of alpha-mannosidase U. Alpha-mannosidase S activity in sera is significantly higher in children than in adults."}
{"id": "PMID:238753", "title": "Control of myocardial oxygen tension by sympathetic coronary vasoconstriction in the dog.", "content": "The effect of sympathetic alpha-receptor coronary vasoconstriction on myocardial oxygen tension was studied in open- and closed-chest, chloralose-anesthetized dogs. Blood oxygen tension in the coronary sinus and blood flow in the circumflex coronary artery were continuously measured in a three-part experiment. With stimulation of the left stellate ganglion (15 Hz, 3 msec, 4-7 v, 90-second train) under vagotomy control conditions (part 1), heart rate, blood pressure, and coronary blood flow increased, but coronary sinus oxygen tension decreased from 19 mm Hg to 15 mm Hg. In part 2, beta-receptor blockade with propranolol (2.0 mg/kg. iv) in the same dogs blunted the positive inotropic and chronotropic effects of sympathetic stimulation; coronary alpha-receptor vasoconstriction was unmasked, and coronary sinus blood oxygen tension fell from 17 mm Hg to 11 mm Hg. Since increases in oxygen metabolism were blunted, it appeared that the decrease in coronary sinus oxygen tension was caused by alpha-receptor coronary artery vasoconstriction. This hypothesis was tested in part 3 by the addition of alpha-receptor blockade with Dibozane (3.0 mg/kg, iv). Sympathetic stimulation no longer resulted in a change in either coronary vascular resistance or coronary sinus oxygen tension. These results indicate that the fall in oxygen tension during beta-receptor blockade in part 2 was due to alpha-receptor coronary vasoconstriction. Thus, myocardial oxygen tension may be regulated by coronary sympathetic vasomotion as well as by myocardial oxygen metabolism and local vascular control mechanisms.", "contents": "Control of myocardial oxygen tension by sympathetic coronary vasoconstriction in the dog. The effect of sympathetic alpha-receptor coronary vasoconstriction on myocardial oxygen tension was studied in open- and closed-chest, chloralose-anesthetized dogs. Blood oxygen tension in the coronary sinus and blood flow in the circumflex coronary artery were continuously measured in a three-part experiment. With stimulation of the left stellate ganglion (15 Hz, 3 msec, 4-7 v, 90-second train) under vagotomy control conditions (part 1), heart rate, blood pressure, and coronary blood flow increased, but coronary sinus oxygen tension decreased from 19 mm Hg to 15 mm Hg. In part 2, beta-receptor blockade with propranolol (2.0 mg/kg. iv) in the same dogs blunted the positive inotropic and chronotropic effects of sympathetic stimulation; coronary alpha-receptor vasoconstriction was unmasked, and coronary sinus blood oxygen tension fell from 17 mm Hg to 11 mm Hg. Since increases in oxygen metabolism were blunted, it appeared that the decrease in coronary sinus oxygen tension was caused by alpha-receptor coronary artery vasoconstriction. This hypothesis was tested in part 3 by the addition of alpha-receptor blockade with Dibozane (3.0 mg/kg, iv). Sympathetic stimulation no longer resulted in a change in either coronary vascular resistance or coronary sinus oxygen tension. These results indicate that the fall in oxygen tension during beta-receptor blockade in part 2 was due to alpha-receptor coronary vasoconstriction. Thus, myocardial oxygen tension may be regulated by coronary sympathetic vasomotion as well as by myocardial oxygen metabolism and local vascular control mechanisms."}
{"id": "PMID:238754", "title": "Effects of neurotransmitters injected into the posterior and the anterior septal artery on the automaticity of the atrioventricular junctional area of the dog heart.", "content": "The effects of neurotransmitters injected into the posterior and the anterior septal artery on the automaticity of the atrioventricular (AV) junctional area were examined in the excised, blood-perfused canine AV node preparation. An AV rhythm of 57.4 +/- 2.8 beats/min (N = 28) developed after the destruction of the sinoatrial node. l-Norepinephrine injected into the anterior septal artery increased the frequency of AV rhythm, but l-norepinephrine injected into the posterior septal artery caused a pacemaker shift from the anterior septal artery area to the posterior septal artery area. Acetylcholine injected into the posterior septal artery blocked retrograde conduction but did not decrease the frequency of AV rhythm; however, acetylcholine injected into the anterior septal artery decreased AV rhythm but did not affect retrograde conduction. Destruction of the posterior septal artery area failed to change AV rhythm. The surgically separated anterior septal artery preparation had the same rate as did the AV node preparation. The posterior septal artery preparation had a definitely lower rate and responded to smaller doses of l-norepinephrine than did the AV node preparation. The results of the present study indicate that AV rhythm in the AV node originates in the area supplied by the anterior septal artery and that the area supplied by the posterior septal artery, which has extremely low automaticity, is highly responsive to l-norepinephrine, resulting in nodal tachycardia.", "contents": "Effects of neurotransmitters injected into the posterior and the anterior septal artery on the automaticity of the atrioventricular junctional area of the dog heart. The effects of neurotransmitters injected into the posterior and the anterior septal artery on the automaticity of the atrioventricular (AV) junctional area were examined in the excised, blood-perfused canine AV node preparation. An AV rhythm of 57.4 +/- 2.8 beats/min (N = 28) developed after the destruction of the sinoatrial node. l-Norepinephrine injected into the anterior septal artery increased the frequency of AV rhythm, but l-norepinephrine injected into the posterior septal artery caused a pacemaker shift from the anterior septal artery area to the posterior septal artery area. Acetylcholine injected into the posterior septal artery blocked retrograde conduction but did not decrease the frequency of AV rhythm; however, acetylcholine injected into the anterior septal artery decreased AV rhythm but did not affect retrograde conduction. Destruction of the posterior septal artery area failed to change AV rhythm. The surgically separated anterior septal artery preparation had the same rate as did the AV node preparation. The posterior septal artery preparation had a definitely lower rate and responded to smaller doses of l-norepinephrine than did the AV node preparation. The results of the present study indicate that AV rhythm in the AV node originates in the area supplied by the anterior septal artery and that the area supplied by the posterior septal artery, which has extremely low automaticity, is highly responsive to l-norepinephrine, resulting in nodal tachycardia."}
{"id": "PMID:238755", "title": "Upper limit of cerebral blood flow autoregulation in experimental renovascular hypertension in the baboon.", "content": "The effect of arterial hypertension on cerebral blood flow was studied by the intracarotid 133Xe clearance method in baboons. The arterial blood pressure was raised in gradual steps with angiotensin. Baboons with renal hypertension of 8-12 weeks duration were studied along with normotensive baboons. In initially normotensive baboons, cerebral blood flow remained constant until the mean arterial blood pressure had risen to the range of 140 to 154 mm Hg; thereafter cerebral blood flow increased with each rise in mean arterial blood pressure. In the chronically hypertensive baboons, cerebral blood flow remained constant until the mean arterial blood pressure had been elevated to the range of 155 to 169 mm Hg. Thus, in chronic hypertension it appears that there are adaptive changes in the cerebral circulation which may help to protect the brain from further increases in arterial blood pressure.", "contents": "Upper limit of cerebral blood flow autoregulation in experimental renovascular hypertension in the baboon. The effect of arterial hypertension on cerebral blood flow was studied by the intracarotid 133Xe clearance method in baboons. The arterial blood pressure was raised in gradual steps with angiotensin. Baboons with renal hypertension of 8-12 weeks duration were studied along with normotensive baboons. In initially normotensive baboons, cerebral blood flow remained constant until the mean arterial blood pressure had risen to the range of 140 to 154 mm Hg; thereafter cerebral blood flow increased with each rise in mean arterial blood pressure. In the chronically hypertensive baboons, cerebral blood flow remained constant until the mean arterial blood pressure had been elevated to the range of 155 to 169 mm Hg. Thus, in chronic hypertension it appears that there are adaptive changes in the cerebral circulation which may help to protect the brain from further increases in arterial blood pressure."}
{"id": "PMID:238756", "title": "Alpha-receptor stimulation by endogenous and exogenous norepinephrine and blockade by phentolamine in pial arteries of cats.", "content": "The question regarding the existence of an alpha-adrenergic component of pial arterial tone was investigated using a microapplication technique combined with the measurement of vascular diameter. Concentration-response curves for the alpha-receptor blocker, phentolamine, revealed no vascular reaction for a concentration range from 2.5 x 10(-11) to 2.5 x 10(-7) M. At higher concentrations (up to 1.3 x 10(-3) M) concentration-dependent dilations were observed. Constrictions of pial arteries induced by perivascular injection of 2.5 x 10(-6) M norepinephrine could be reduced by 38% and 73% when phentolamine was applied simultaneously in concentrations of 2.5 x 10(-7) and 2.5 x 10(-6) M, respectively, whereas constrictions due to 2.5 x 10(-4) M norepinephrine were not reduced by 2.5 x 10(-6) M phentolamine, indicating a competitive antagonism between norepinephrine and phentolamine for pial arteries. Stimulation of the cervical sympathetic chain (90 seconds, 10 v, 1.4 msec, 20 Hz) induced constrictions of pial arteries (mean 12%) which could be reduced by two-thirds during the simultaneous application of 2.5 x 10(-7) M phentolamine. Since the constriction induced by norepinephrine applied exogenously or released endogenously could be reduced by a concentration of phentolamine which had no vascular effect per se, we conclude that the resting tone of the pial arteries is not influenced by an alpha-adrenergic component under our experimental conditions. The dilations induced by high concentrations of phentolamine are believed to be nonspecific.", "contents": "Alpha-receptor stimulation by endogenous and exogenous norepinephrine and blockade by phentolamine in pial arteries of cats. The question regarding the existence of an alpha-adrenergic component of pial arterial tone was investigated using a microapplication technique combined with the measurement of vascular diameter. Concentration-response curves for the alpha-receptor blocker, phentolamine, revealed no vascular reaction for a concentration range from 2.5 x 10(-11) to 2.5 x 10(-7) M. At higher concentrations (up to 1.3 x 10(-3) M) concentration-dependent dilations were observed. Constrictions of pial arteries induced by perivascular injection of 2.5 x 10(-6) M norepinephrine could be reduced by 38% and 73% when phentolamine was applied simultaneously in concentrations of 2.5 x 10(-7) and 2.5 x 10(-6) M, respectively, whereas constrictions due to 2.5 x 10(-4) M norepinephrine were not reduced by 2.5 x 10(-6) M phentolamine, indicating a competitive antagonism between norepinephrine and phentolamine for pial arteries. Stimulation of the cervical sympathetic chain (90 seconds, 10 v, 1.4 msec, 20 Hz) induced constrictions of pial arteries (mean 12%) which could be reduced by two-thirds during the simultaneous application of 2.5 x 10(-7) M phentolamine. Since the constriction induced by norepinephrine applied exogenously or released endogenously could be reduced by a concentration of phentolamine which had no vascular effect per se, we conclude that the resting tone of the pial arteries is not influenced by an alpha-adrenergic component under our experimental conditions. The dilations induced by high concentrations of phentolamine are believed to be nonspecific."}
{"id": "PMID:238757", "title": "Cerebrospinal fluid acidosis complicating therapy of experimental cardiopulmonary arrest.", "content": "Cardiopulmonary resuscitation (CPR) may be followed by slow recovery of brain function. The possible role of bicarbonate therapy was assessed by analysis of arterial blood and cerebrospinal fluid (CSF) in 20 dogs during cardiac arrest and CPR. Samples were taken in the control period and every 5 minutes post-arrest of 20 minutes. Group I received no post-arrest CPR. Arterial pH fell from 7.37 to 7.31 (P less than 0.01) and CSF pH from 7.34 to 6.94 (P less than 0.001). Arterial pCO2 rose from 39 to 65 mm Hg (P less than 0.005) and CSF pCO2 increased from 47 to 123 (P less than 0.02). With CPR alone (group II) arterial pH decreased from 7.39 to 7.19 (P less than 0.005), while arterial pCO2 and CSF pH and pCO2 were undhanged. CPR with bicarbonate therapy (mEq = weight in kg times 0.43 times 1.1 mEq/min of arrest) given every 5 minutes (group III), resulted in a rise in arterial pH from 7.41 to 7.81 (P less than 0.02). Excess bicarbonate administration during CPR may result in a marked dissociation between arterial and CSF pH as a consequence of rapid CO2 diffusion across the blood-brain barrier. Large ampounts of NaHCO3 given during CPR may contribute to post-CPR cerebral depresssion.", "contents": "Cerebrospinal fluid acidosis complicating therapy of experimental cardiopulmonary arrest. Cardiopulmonary resuscitation (CPR) may be followed by slow recovery of brain function. The possible role of bicarbonate therapy was assessed by analysis of arterial blood and cerebrospinal fluid (CSF) in 20 dogs during cardiac arrest and CPR. Samples were taken in the control period and every 5 minutes post-arrest of 20 minutes. Group I received no post-arrest CPR. Arterial pH fell from 7.37 to 7.31 (P less than 0.01) and CSF pH from 7.34 to 6.94 (P less than 0.001). Arterial pCO2 rose from 39 to 65 mm Hg (P less than 0.005) and CSF pCO2 increased from 47 to 123 (P less than 0.02). With CPR alone (group II) arterial pH decreased from 7.39 to 7.19 (P less than 0.005), while arterial pCO2 and CSF pH and pCO2 were undhanged. CPR with bicarbonate therapy (mEq = weight in kg times 0.43 times 1.1 mEq/min of arrest) given every 5 minutes (group III), resulted in a rise in arterial pH from 7.41 to 7.81 (P less than 0.02). Excess bicarbonate administration during CPR may result in a marked dissociation between arterial and CSF pH as a consequence of rapid CO2 diffusion across the blood-brain barrier. Large ampounts of NaHCO3 given during CPR may contribute to post-CPR cerebral depresssion."}
{"id": "PMID:238758", "title": "Radioimmunoassay for triiodothyronine: use of polyethylene glycol to precipitate immune complexes.", "content": "1. A rapid radioimmunoassay (RIA) for determining serum triiodothyronine (T3) concentration has been developed. The reaction of T3 with its antibody was performed at 37 degrees C for 3 hours; precipitation of antibody bound T3 by 15% polyethylene glycol (PEG) was done at ice-bath temperatures. 2. The effects of pH on the interaction of T3 with its antibody and on the precipitation of antibody gamman globulin by PEG are discussed. 3. PEG precipitates and supernatants were characterized by immunoelectrophoresis and polyacrylamide gel electrophoresis. 4. The RIA has a between run precision of 9.3% at a mean T3 concentration of 179 ng/dl. The recovery of 50 or 100 ng/dl T3 was 95-102% and the normal range estimate was 66-215 ng/dl (N equal to 49).", "contents": "Radioimmunoassay for triiodothyronine: use of polyethylene glycol to precipitate immune complexes. 1. A rapid radioimmunoassay (RIA) for determining serum triiodothyronine (T3) concentration has been developed. The reaction of T3 with its antibody was performed at 37 degrees C for 3 hours; precipitation of antibody bound T3 by 15% polyethylene glycol (PEG) was done at ice-bath temperatures. 2. The effects of pH on the interaction of T3 with its antibody and on the precipitation of antibody gamman globulin by PEG are discussed. 3. PEG precipitates and supernatants were characterized by immunoelectrophoresis and polyacrylamide gel electrophoresis. 4. The RIA has a between run precision of 9.3% at a mean T3 concentration of 179 ng/dl. The recovery of 50 or 100 ng/dl T3 was 95-102% and the normal range estimate was 66-215 ng/dl (N equal to 49)."}
{"id": "PMID:238759", "title": "Defective heparan sulfate metabolism in the Sanfilippo syndrome and assay of this defect in the assessment of the mucopolysaccharidoses patient.", "content": "The Sanifilippo syndrome is an inherited dementia caused by defective degradation of heparan sulfate. In the course of its catabolism the heparan sulfate polymer must be desulfated. Heparan sulfate sulfatase activity was demonstrated in homogenates of normal tissues and cultured skin fibroblasts, and in normal urine. This activity was found to be grossly depressed or absent in necropsy specimens of liver and spleen from two Sanfilippo patients. The heparan sulfate sulfatase activity was not demonstrable in urine from eleven, or cultured fibroblasts from four Sanfilippo patients. Activities of alpha-N-acetyl-glucosaminidase, the site of the metabolic defect in the Sanfilippo B variant were either normal or slightly elevated in the Sanfilippo tissues and cultured fibroblasts whereas the mean level in the urine of our Sanfilippo patients was about one-third of that encountered in control urines.", "contents": "Defective heparan sulfate metabolism in the Sanfilippo syndrome and assay of this defect in the assessment of the mucopolysaccharidoses patient. The Sanifilippo syndrome is an inherited dementia caused by defective degradation of heparan sulfate. In the course of its catabolism the heparan sulfate polymer must be desulfated. Heparan sulfate sulfatase activity was demonstrated in homogenates of normal tissues and cultured skin fibroblasts, and in normal urine. This activity was found to be grossly depressed or absent in necropsy specimens of liver and spleen from two Sanfilippo patients. The heparan sulfate sulfatase activity was not demonstrable in urine from eleven, or cultured fibroblasts from four Sanfilippo patients. Activities of alpha-N-acetyl-glucosaminidase, the site of the metabolic defect in the Sanfilippo B variant were either normal or slightly elevated in the Sanfilippo tissues and cultured fibroblasts whereas the mean level in the urine of our Sanfilippo patients was about one-third of that encountered in control urines."}
{"id": "PMID:238763", "title": "An investigation of some factors affecting levels of erythrocyte inorganic pyrophosphatase activity.", "content": "A reproducible method has been devised for assaying erythrocyte inorganic pyrophosphatase. The activity level in healthy individuals appears to be a constant characteristic. Population surveys have been carried out in 100 Europeans and 34 Indians. In each population an otherwise normal individual was found with activity approximately three standard deviations from the mean. Investigation of the family of one such individual indicated that this was an inherited characteristic. A few individuals with clinical abnormalities were examined and some were found to have activity levels above the normal range. High activity levels appeared to be associated with those diseases in which raised circulating reticulocyte levels are found. The rate of in vivo decay of erythrocyte inorganice pyrophosphatase has been measured in healthy individuals. The decay pattern appears to be of the constant logarithmic type. An estimate has been made of the activity in circulating reticulocytes, and the half life of the enzymes has been calculated.", "contents": "An investigation of some factors affecting levels of erythrocyte inorganic pyrophosphatase activity. A reproducible method has been devised for assaying erythrocyte inorganic pyrophosphatase. The activity level in healthy individuals appears to be a constant characteristic. Population surveys have been carried out in 100 Europeans and 34 Indians. In each population an otherwise normal individual was found with activity approximately three standard deviations from the mean. Investigation of the family of one such individual indicated that this was an inherited characteristic. A few individuals with clinical abnormalities were examined and some were found to have activity levels above the normal range. High activity levels appeared to be associated with those diseases in which raised circulating reticulocyte levels are found. The rate of in vivo decay of erythrocyte inorganice pyrophosphatase has been measured in healthy individuals. The decay pattern appears to be of the constant logarithmic type. An estimate has been made of the activity in circulating reticulocytes, and the half life of the enzymes has been calculated."}
{"id": "PMID:238764", "title": "A pH-dependent macroglobulin gel.", "content": "Plasma from a patient with Waldenstrom's macroglobulinemia was observed to gel upon exposure to room air, yet to remain in solution indefinitely at 4 degrees C if sealed. Three studies were carried out which showed this change not to be due primarily to decreases in carbon dioxide tension or temperature, but to variations in the concentration of hydrogen ions within or just above physiologic levels. In purified material (IgM) a marked increase in viscosity occurred between pH 7.5 and 8.0, followed by precipitation between pH 8.0 and 9.7, and by reversible dissolution between pH 9.7 and 10.0. The analytical and clinical consequences of these solubility changes are discussed.", "contents": "A pH-dependent macroglobulin gel. Plasma from a patient with Waldenstrom's macroglobulinemia was observed to gel upon exposure to room air, yet to remain in solution indefinitely at 4 degrees C if sealed. Three studies were carried out which showed this change not to be due primarily to decreases in carbon dioxide tension or temperature, but to variations in the concentration of hydrogen ions within or just above physiologic levels. In purified material (IgM) a marked increase in viscosity occurred between pH 7.5 and 8.0, followed by precipitation between pH 8.0 and 9.7, and by reversible dissolution between pH 9.7 and 10.0. The analytical and clinical consequences of these solubility changes are discussed."}
{"id": "PMID:238765", "title": "[Quantitative determination of IgA from human bronchial mucus (author's transl)].", "content": "Before quantitative analysis of bronchial mucus proteins, sputum must be transformed into a homogeneous medium: this is done by ultrasonic action and contact with cationic resin AG 50 W X 2. Then, acid mucins are fixed on Ecteola-cellulose, and proteins extracted by a phosphate/saline buffer at pH 5. IgA is estimated by electroimmunodiffusion. Reproducibility of the method is discussed: the accuracy for IgA values is 4%.", "contents": "[Quantitative determination of IgA from human bronchial mucus (author's transl)]. Before quantitative analysis of bronchial mucus proteins, sputum must be transformed into a homogeneous medium: this is done by ultrasonic action and contact with cationic resin AG 50 W X 2. Then, acid mucins are fixed on Ecteola-cellulose, and proteins extracted by a phosphate/saline buffer at pH 5. IgA is estimated by electroimmunodiffusion. Reproducibility of the method is discussed: the accuracy for IgA values is 4%."}
{"id": "PMID:238767", "title": "[Improvements in the technical conditions for the evaluation of an elastolytic activity. The role of tryspin as an activator (author's transl)].", "content": "An isotopic assay of elastolytic activity is performed; the iodine-125 ions retained inside the elastin framework were removed by appropriate treatment. This acute substrate enables us to study the role of trypsin on elastase activity and facilitates the study of elastase role in atherosclerosis.", "contents": "[Improvements in the technical conditions for the evaluation of an elastolytic activity. The role of tryspin as an activator (author's transl)]. An isotopic assay of elastolytic activity is performed; the iodine-125 ions retained inside the elastin framework were removed by appropriate treatment. This acute substrate enables us to study the role of trypsin on elastase activity and facilitates the study of elastase role in atherosclerosis."}
{"id": "PMID:238768", "title": "[Isoenzymes of alanine arylamidase (AAP, EC 3.4.11.2) and gamma-glutamyltranspeptidase (GGTP, EC 2.3.2.2) in chronic pancreatitis and pancreas neoplasm (author's transl)].", "content": "In 22 patients with chronic pancreatitis and 16 patients with pancreas neoplasms gamma-glutamyltranspeptidase (GGTP) and alanine arylamidase (AAP) in serum were measured and the isoenzymes were determined by gel electrophoresis on Agar. No specific isoenzyme pattern was found for chronic pancreatic diseases in a comparative investigation with a group of 19 patients suffering from hepatobiliary diseases. Two fractions of AAP and GGTP isoenzymes were found on agar gel electrophoresis: alpha-1 and alpha-2 (GGTP between alpha-2 and beta-globulin). The alpha-1 fraction of AAP and GGTP seems to be a specific liver isoenzyme. The slower fraction of both enzymes was also found in chronic pancreatic diseases and cholestatic diseases as in neoplasms of liver, pancreas and biliary tract. Practical importance of the findings is diminished by large variation coefficients of the results. A significantly low ratio of alpha-1 to alpha-2 fraction (or beta-globulin) on electrophoresis of the isoenzymes of AAP and GGTP was found in the group with neoplasm of pancreas (especially neoplasm of the pancreas head) as compared to the group with intrahepatic cholestasis. The possible causes and diagnostic importance of the findings are discussed.", "contents": "[Isoenzymes of alanine arylamidase (AAP, EC 3.4.11.2) and gamma-glutamyltranspeptidase (GGTP, EC 2.3.2.2) in chronic pancreatitis and pancreas neoplasm (author's transl)]. In 22 patients with chronic pancreatitis and 16 patients with pancreas neoplasms gamma-glutamyltranspeptidase (GGTP) and alanine arylamidase (AAP) in serum were measured and the isoenzymes were determined by gel electrophoresis on Agar. No specific isoenzyme pattern was found for chronic pancreatic diseases in a comparative investigation with a group of 19 patients suffering from hepatobiliary diseases. Two fractions of AAP and GGTP isoenzymes were found on agar gel electrophoresis: alpha-1 and alpha-2 (GGTP between alpha-2 and beta-globulin). The alpha-1 fraction of AAP and GGTP seems to be a specific liver isoenzyme. The slower fraction of both enzymes was also found in chronic pancreatic diseases and cholestatic diseases as in neoplasms of liver, pancreas and biliary tract. Practical importance of the findings is diminished by large variation coefficients of the results. A significantly low ratio of alpha-1 to alpha-2 fraction (or beta-globulin) on electrophoresis of the isoenzymes of AAP and GGTP was found in the group with neoplasm of pancreas (especially neoplasm of the pancreas head) as compared to the group with intrahepatic cholestasis. The possible causes and diagnostic importance of the findings are discussed."}
{"id": "PMID:238769", "title": "Purification and characterization of human erythrocyte pyridoxine kinase.", "content": "A 6000-fold purification of pyridoxine kinase from human erythrocytes has been achieved by a combination of DEAE-cellulose chromatography, ammonium sulfate fractionation, gel filtration and preparative disc polyacrylamide gel electrophoresis. Analytic disc polyacrylamide gel electrophoresis at pH 8.7 reveals two protein bands with similar mobility in the purified enzyme, but only one of these has catalytic activity. The enzyme is found to have a pI of 5.5 and a molecular weight of 65000 by gel filtration, and a broad pH optimum of 8.5. The enzyme is labile at acidic pH. The order of activation of divalent metal ions on the enzyme is Co-2+ greater than Mn-2+ greater than Mg-2+ greater than Zn-2+ greater than Cu-2+ greater than Ni-2+ greater than Fe-2+. Of the monovalent cations studied, K+ is the most effective activator, NH+4 is slightly less effective while Na+ is inhibitory. ATP is the specific phosphate donor for the enzyme. Sulfhydryl reagents did not significantly inhibit the enzyme. The Km for pyridoxine is 5.7 with 10-minus 6 M. Pyridoxal, pyridoxamine and 4-deoxypyridoxine inhibit pyridoxine kinase. Inhibition by pyridoxal is competitive and pyridoxal is observed to be phosphorylated effectively by the enzyme. Young human red cells have a higher activity of pyridoxine kinase than old red cells.", "contents": "Purification and characterization of human erythrocyte pyridoxine kinase. A 6000-fold purification of pyridoxine kinase from human erythrocytes has been achieved by a combination of DEAE-cellulose chromatography, ammonium sulfate fractionation, gel filtration and preparative disc polyacrylamide gel electrophoresis. Analytic disc polyacrylamide gel electrophoresis at pH 8.7 reveals two protein bands with similar mobility in the purified enzyme, but only one of these has catalytic activity. The enzyme is found to have a pI of 5.5 and a molecular weight of 65000 by gel filtration, and a broad pH optimum of 8.5. The enzyme is labile at acidic pH. The order of activation of divalent metal ions on the enzyme is Co-2+ greater than Mn-2+ greater than Mg-2+ greater than Zn-2+ greater than Cu-2+ greater than Ni-2+ greater than Fe-2+. Of the monovalent cations studied, K+ is the most effective activator, NH+4 is slightly less effective while Na+ is inhibitory. ATP is the specific phosphate donor for the enzyme. Sulfhydryl reagents did not significantly inhibit the enzyme. The Km for pyridoxine is 5.7 with 10-minus 6 M. Pyridoxal, pyridoxamine and 4-deoxypyridoxine inhibit pyridoxine kinase. Inhibition by pyridoxal is competitive and pyridoxal is observed to be phosphorylated effectively by the enzyme. Young human red cells have a higher activity of pyridoxine kinase than old red cells."}
{"id": "PMID:238770", "title": "Production and storage of (125-I) thyroxine and (125-I) triiodothyronine of high specific activity.", "content": "High specific activity [125-I] triiodothyronine and [125-I] thyroxine have been produced regularly by the chloramine T radioiodination method. Simultaneous production of [125-I] triiodothyronine and [125-I] thyroxine is usual when diiodothyronine or triiodothyronine are employed as the starting materials. Specific activities reached vary with the starting compound (diiodothyronine, triiodothyronine, thyroxine) used, as both substitution and, less readily, exchange of iodine atoms take place. Starting with diiodothyronine specific activities of approximately 2400 and 5200 Ci/g were achieved for [125-I]triidothyronine and [125I] thyroxine, respectively, and, similarly, specific activities of approximately 1200 and 4000 Ci/g for [125I] triiodothyronine and [125I]-thyroxine, respectively, were reached when triiodothyronine was the starting material. [125-I] Triiodoacetic acid and [125I] tetraiodoacetic acid have been produced in the same way from triiodoacetic acid. By column chromatography on Sephadex G-25 (fine), eluting with alkaline phosphate buffer, good separation of the radioiodinated products has been readily achieved. Studies on the stability of the radioiodinated hormones showed that 50% methanol, ethanol, propanol and propylene glycol were all equivalent as preserving agents and, further, that the stability of the radioiodinated hormones was linearly related to the concentration of these preserving agents.", "contents": "Production and storage of (125-I) thyroxine and (125-I) triiodothyronine of high specific activity. High specific activity [125-I] triiodothyronine and [125-I] thyroxine have been produced regularly by the chloramine T radioiodination method. Simultaneous production of [125-I] triiodothyronine and [125-I] thyroxine is usual when diiodothyronine or triiodothyronine are employed as the starting materials. Specific activities reached vary with the starting compound (diiodothyronine, triiodothyronine, thyroxine) used, as both substitution and, less readily, exchange of iodine atoms take place. Starting with diiodothyronine specific activities of approximately 2400 and 5200 Ci/g were achieved for [125-I]triidothyronine and [125I] thyroxine, respectively, and, similarly, specific activities of approximately 1200 and 4000 Ci/g for [125I] triiodothyronine and [125I]-thyroxine, respectively, were reached when triiodothyronine was the starting material. [125-I] Triiodoacetic acid and [125I] tetraiodoacetic acid have been produced in the same way from triiodoacetic acid. By column chromatography on Sephadex G-25 (fine), eluting with alkaline phosphate buffer, good separation of the radioiodinated products has been readily achieved. Studies on the stability of the radioiodinated hormones showed that 50% methanol, ethanol, propanol and propylene glycol were all equivalent as preserving agents and, further, that the stability of the radioiodinated hormones was linearly related to the concentration of these preserving agents."}
{"id": "PMID:238771", "title": "A comparison of canine normal hepatic alkaline phosphatase and variant alkaline phosphatase of serum and liver.", "content": "The isoenzyme of alkaline phosphatase from normal liver, the corticosteroid induced isoenzyme of alkaline phosphatase from serum and liver and a hepatocellular variant isoenzyme of alkaline phosphatase induced by lymphosarcoma have been partially purified and their the present modification incorporates Polybrene into buffer to eliminate this heparin interference. The proposed method shown excellent agreement with a reference procedure based on clottable protein, and excellent day-to-day precision (C.V.3.5%). The present method is easily adaptable to semi-automated measurements.", "contents": "A comparison of canine normal hepatic alkaline phosphatase and variant alkaline phosphatase of serum and liver. The isoenzyme of alkaline phosphatase from normal liver, the corticosteroid induced isoenzyme of alkaline phosphatase from serum and liver and a hepatocellular variant isoenzyme of alkaline phosphatase induced by lymphosarcoma have been partially purified and their the present modification incorporates Polybrene into buffer to eliminate this heparin interference. The proposed method shown excellent agreement with a reference procedure based on clottable protein, and excellent day-to-day precision (C.V.3.5%). The present method is easily adaptable to semi-automated measurements."}
{"id": "PMID:238774", "title": "Specific control of follicle stimulating hormone in the male: postulated site of action of inhibin.", "content": "Serum luteinizing and follicle stimulating hormone concentrations were related to gonadal function, as reflected by sperm count and serum testosterone concentrations, in a group of men studied over 10 years after surgical correction of bilateral cryptorchidism in childhood. The results indicated that while all degrees of gonadal function occurred in these patients, the main adverse effect of cryptorchidism was on spermatogenesis. In some of the patients with oligospermia and normal Leydig cell function there was an isolated increase of basal serum FSH concentrations, suggesting a specific impairment of the testicular production of 'inhibin'. Gonadotrophin releasing hormone (LHRH) tests in these patients were compared to those in patients with normal basal gonadotrophins and to those with elevated basal LH and FSH concentrations. A selective exaggeration of the FSH response to exogenous LHRH in the group of patients with a monotropic elevation of FSH concentrations suggests that 'inhibin' modulates the secretion of FSH by an action on the pituitary rather than by modifying endogenous LHRH production by the hypothalamus.", "contents": "Specific control of follicle stimulating hormone in the male: postulated site of action of inhibin. Serum luteinizing and follicle stimulating hormone concentrations were related to gonadal function, as reflected by sperm count and serum testosterone concentrations, in a group of men studied over 10 years after surgical correction of bilateral cryptorchidism in childhood. The results indicated that while all degrees of gonadal function occurred in these patients, the main adverse effect of cryptorchidism was on spermatogenesis. In some of the patients with oligospermia and normal Leydig cell function there was an isolated increase of basal serum FSH concentrations, suggesting a specific impairment of the testicular production of 'inhibin'. Gonadotrophin releasing hormone (LHRH) tests in these patients were compared to those in patients with normal basal gonadotrophins and to those with elevated basal LH and FSH concentrations. A selective exaggeration of the FSH response to exogenous LHRH in the group of patients with a monotropic elevation of FSH concentrations suggests that 'inhibin' modulates the secretion of FSH by an action on the pituitary rather than by modifying endogenous LHRH production by the hypothalamus."}
{"id": "PMID:238780", "title": "The separate modes and sites of action of furosemide and amiloride.", "content": "The effect of furosemide and amiloride on the transport of sodium, potassium, hydrogen and bicarbonate ions was studied in microperfusion experiments on the main excretory duct of the submaxillary gland of the rat. Furosemide did not impair transport of Na+, K+ and H+/HCO-3. Amiloride, however, completely abolished Na+ transport. Blockade of Na+ transport was accompanied by abolition of passive K+ secretion, whereas the active components of K+ and HCO-3 secretion were not affected. In urinary excretion studies, amiloride, which is known to block sodium transport selectively, was used in order to assess whether furosemide has a distinct effect that is independent of sodium transport. Oral administration of amiloride caused a selective excretion of Na+ in a more alkaline urine with an extremely low K+ concentration. The injection of furosemide caused a copious diuresis of an isotonic urine, in which excretion of Na+ and K+ was balanced by the excretion of Cl- ions. Combined administration of amiloride and furosemide produced summation of the individual effects of both diuretics, indicating that the two drugs had different sites and modes of action. In the presence of furosemide the kidney no longer responded to antidiuretic hormone, which suggested that the urine concentrating mechanism in Henle's loop was blocked by furosemide.", "contents": "The separate modes and sites of action of furosemide and amiloride. The effect of furosemide and amiloride on the transport of sodium, potassium, hydrogen and bicarbonate ions was studied in microperfusion experiments on the main excretory duct of the submaxillary gland of the rat. Furosemide did not impair transport of Na+, K+ and H+/HCO-3. Amiloride, however, completely abolished Na+ transport. Blockade of Na+ transport was accompanied by abolition of passive K+ secretion, whereas the active components of K+ and HCO-3 secretion were not affected. In urinary excretion studies, amiloride, which is known to block sodium transport selectively, was used in order to assess whether furosemide has a distinct effect that is independent of sodium transport. Oral administration of amiloride caused a selective excretion of Na+ in a more alkaline urine with an extremely low K+ concentration. The injection of furosemide caused a copious diuresis of an isotonic urine, in which excretion of Na+ and K+ was balanced by the excretion of Cl- ions. Combined administration of amiloride and furosemide produced summation of the individual effects of both diuretics, indicating that the two drugs had different sites and modes of action. In the presence of furosemide the kidney no longer responded to antidiuretic hormone, which suggested that the urine concentrating mechanism in Henle's loop was blocked by furosemide."}
{"id": "PMID:238781", "title": "A complex pattern of disposition of phenytoin in severe intoxication.", "content": "A 5-year-old child developed phenytoin (diphenylhydantoin, DPH) toxicity after receiving 500 mg of the drug daily for 3 weeks. Plasma, urine, and duodenal fluid were collected for assay of DPH and its metabolites. The peak plasma concentration of DPH was 108 mug/ml, and the decline in plasma level did not fit first-order kinetics. The para-hydroxy, meta-hydroxy, and dihydrodiol metabolites of DPH were measured in urine; duodenal aspirate contained both DPH and the para-hydroxy metabolite. Plasma pH may affect distribution of DPH since in vitro binding of DPH to human albumin increased as pH increased.", "contents": "A complex pattern of disposition of phenytoin in severe intoxication. A 5-year-old child developed phenytoin (diphenylhydantoin, DPH) toxicity after receiving 500 mg of the drug daily for 3 weeks. Plasma, urine, and duodenal fluid were collected for assay of DPH and its metabolites. The peak plasma concentration of DPH was 108 mug/ml, and the decline in plasma level did not fit first-order kinetics. The para-hydroxy, meta-hydroxy, and dihydrodiol metabolites of DPH were measured in urine; duodenal aspirate contained both DPH and the para-hydroxy metabolite. Plasma pH may affect distribution of DPH since in vitro binding of DPH to human albumin increased as pH increased."}
{"id": "PMID:238777", "title": "Beta-adrenoreceptors in denervated skeletal muscles of the cat.", "content": "1. A number of sympathomimetic amines have been compared with (-)-isoprenaline for their ability to produce contractions in chronically denervated soleus and tibialis anterior muscles and to increase heart rate in bilaterally vagotomized anaesthetized cats. 2. The mean dose-ratios ((-)-isoprenaline equals 1) for adrenaline, orciprenaline and salbutamol were 2.9, 29.7 and 11.5 respectively in the tibialis anterior muscle and 3.5, 24.1 and 14.3 in the soleus muscle. The dose-ratios for noradrenaline were 21.1 in the tibialis anterior and 57.6 in the soleus muscle. 3. The dose-ratios ((-)-isoprenaline equals 1) obtained for the positive chronotropic effects of the drugs in bilaterally vagotomized cats were 14.5, 14.6, 29.6 and 24.2 for adrenaline, noradrenaline, orciprenaline and salbutamol respectively. 4. The beta2-receptor antagonists butoxamine and H35/25 antagonized the vasodepressor and skeletal muscle responses to (-)-isoprenaline to a greater extent than the cardiac responses, whereas the beta1-receptor selective antagonists practolol and H93/26 antagonized cardiac to a greater extent than vascular and skeletal muscle responses. 5. The results obtained suggest that the contractions of denervated skeletal muscle to sympathomimetic drugs result from stimulation of beta2-adrenoreceptors.", "contents": "Beta-adrenoreceptors in denervated skeletal muscles of the cat. 1. A number of sympathomimetic amines have been compared with (-)-isoprenaline for their ability to produce contractions in chronically denervated soleus and tibialis anterior muscles and to increase heart rate in bilaterally vagotomized anaesthetized cats. 2. The mean dose-ratios ((-)-isoprenaline equals 1) for adrenaline, orciprenaline and salbutamol were 2.9, 29.7 and 11.5 respectively in the tibialis anterior muscle and 3.5, 24.1 and 14.3 in the soleus muscle. The dose-ratios for noradrenaline were 21.1 in the tibialis anterior and 57.6 in the soleus muscle. 3. The dose-ratios ((-)-isoprenaline equals 1) obtained for the positive chronotropic effects of the drugs in bilaterally vagotomized cats were 14.5, 14.6, 29.6 and 24.2 for adrenaline, noradrenaline, orciprenaline and salbutamol respectively. 4. The beta2-receptor antagonists butoxamine and H35/25 antagonized the vasodepressor and skeletal muscle responses to (-)-isoprenaline to a greater extent than the cardiac responses, whereas the beta1-receptor selective antagonists practolol and H93/26 antagonized cardiac to a greater extent than vascular and skeletal muscle responses. 5. The results obtained suggest that the contractions of denervated skeletal muscle to sympathomimetic drugs result from stimulation of beta2-adrenoreceptors."}
{"id": "PMID:238782", "title": "Disposition of acetylmethadol in relation to pharmacologic action.", "content": "The levels of acetylmethadol and its active biotransformation products were quantitated in the plasma and urine of subjects on acetylmethadol maintenance by the use of solvent extraction and gas-liquid chromatography. The time-course of plasma acetylmethadol, noracetylmethadol, and dinoracetylmethadol over 48 hr was determined concurrently with the time-action of pupillary constriction in 8 subjects receiving an average oral maintenance dose of 50 mg. The plasma level of acetylmethadol reached a peak at 4 hr and had nearly disappeared by 24 hr. The mean apparent half-life was 7 hr. The plasma level of noracetylmethadol peaked at 4 to 8 hr and slowly declined over the next 40 hr. The mean apparent half-life of noracetylmethadol was 48 hr. Dinoracetylmethadol plasma levels remained relatively constant throughout the dosing interval. The miotic effect reached a peak at 8 hr and decayed at a rate slower than that of plasma elimination of acetylmethadol but more rapidly than that of noracetylmethadol and dinoracetylmethadol. Substantial variation in the plasma levels of the compounds was observed in subjects after the same doses. The study indicated that the relatively long duration of opiate effects of acetylmethadol results from biotransformation to active and persistent metabolites.", "contents": "Disposition of acetylmethadol in relation to pharmacologic action. The levels of acetylmethadol and its active biotransformation products were quantitated in the plasma and urine of subjects on acetylmethadol maintenance by the use of solvent extraction and gas-liquid chromatography. The time-course of plasma acetylmethadol, noracetylmethadol, and dinoracetylmethadol over 48 hr was determined concurrently with the time-action of pupillary constriction in 8 subjects receiving an average oral maintenance dose of 50 mg. The plasma level of acetylmethadol reached a peak at 4 hr and had nearly disappeared by 24 hr. The mean apparent half-life was 7 hr. The plasma level of noracetylmethadol peaked at 4 to 8 hr and slowly declined over the next 40 hr. The mean apparent half-life of noracetylmethadol was 48 hr. Dinoracetylmethadol plasma levels remained relatively constant throughout the dosing interval. The miotic effect reached a peak at 8 hr and decayed at a rate slower than that of plasma elimination of acetylmethadol but more rapidly than that of noracetylmethadol and dinoracetylmethadol. Substantial variation in the plasma levels of the compounds was observed in subjects after the same doses. The study indicated that the relatively long duration of opiate effects of acetylmethadol results from biotransformation to active and persistent metabolites."}
{"id": "PMID:238779", "title": "Influence of changes in amine substitution on the beta-adrenoceptor stimulant activity of soterenol and related compounds in the anaesthetized cat.", "content": "1. Three 3-methanesulphonamido, 4-hydroxy ring substituted phenylethanolamines with N-isopropyl (soterenol), N-t-butyl (MJ7999-1) and N-(1-phenyl-t-butyl)(MJ9184-1) amine substituents have been compared with ()-isoprenaline for their ability to produce beta-receptor mediated reductions in serotonin-induced increases in pulmonary resistance, decreases in soleus muscle contractility, and increases in heart rate in anaesthetized cats. For each parameter, the dose of a compound required to produce 50% of its maximal response (ED50) was calculated. 2. For all three parameters ()-isoprenaline was the most potent of the compounds studied, and the rank order of potency of the methanesulphonanilides was MJ9184-1 (N-(1-phenyl-t-butyl))congruent to MJ7999-1 (N-t-butyl) greater than soterenol (N-isopropyl). 3. For each individual drug, molar dose-ratios [drug:()-isoprenaline] were calculated. Ratios for the effects of the compounds on the soleus muscle and in the bronchi were similar. With each compound higher dose-ratios were found in the heart. The rank order for relative beta2-selectivity was soterenol (N-isopropyl) greater than MJ7999-1 (N-t-butyl) congruent to MJ9184-1 (N-(1-phenyl-t-butyl)).", "contents": "Influence of changes in amine substitution on the beta-adrenoceptor stimulant activity of soterenol and related compounds in the anaesthetized cat. 1. Three 3-methanesulphonamido, 4-hydroxy ring substituted phenylethanolamines with N-isopropyl (soterenol), N-t-butyl (MJ7999-1) and N-(1-phenyl-t-butyl)(MJ9184-1) amine substituents have been compared with ()-isoprenaline for their ability to produce beta-receptor mediated reductions in serotonin-induced increases in pulmonary resistance, decreases in soleus muscle contractility, and increases in heart rate in anaesthetized cats. For each parameter, the dose of a compound required to produce 50% of its maximal response (ED50) was calculated. 2. For all three parameters ()-isoprenaline was the most potent of the compounds studied, and the rank order of potency of the methanesulphonanilides was MJ9184-1 (N-(1-phenyl-t-butyl))congruent to MJ7999-1 (N-t-butyl) greater than soterenol (N-isopropyl). 3. For each individual drug, molar dose-ratios [drug:()-isoprenaline] were calculated. Ratios for the effects of the compounds on the soleus muscle and in the bronchi were similar. With each compound higher dose-ratios were found in the heart. The rank order for relative beta2-selectivity was soterenol (N-isopropyl) greater than MJ7999-1 (N-t-butyl) congruent to MJ9184-1 (N-(1-phenyl-t-butyl))."}
{"id": "PMID:238776", "title": "Dose-dependent kinetics of ethotoin in man.", "content": "1. A gas-chromatographic assay for the anticonvulsant drug ethotoin in plasma has been used to establish a kinetic basis for therapy in eight newly diagnosed epileptic patients. 2. Only a small fraction of ethotoin was excreted unchanged. Elimination curves were only rectilinear below a plasma concentration of 8 mg/l. During constant medication plasma concentrations tended to decrease in the first week. Steady-state plasma levels varied considerably between individuals. For all patients the plasma concentration/dose ratio increased with increasing dose. 3. Most of the results point to dose-dependent elimination kinetics in the therapeutic range and parallel what is known for phenytoin. Control of therapy by measurement of plasma levels of ethotoin is accordingly advocated.", "contents": "Dose-dependent kinetics of ethotoin in man. 1. A gas-chromatographic assay for the anticonvulsant drug ethotoin in plasma has been used to establish a kinetic basis for therapy in eight newly diagnosed epileptic patients. 2. Only a small fraction of ethotoin was excreted unchanged. Elimination curves were only rectilinear below a plasma concentration of 8 mg/l. During constant medication plasma concentrations tended to decrease in the first week. Steady-state plasma levels varied considerably between individuals. For all patients the plasma concentration/dose ratio increased with increasing dose. 3. Most of the results point to dose-dependent elimination kinetics in the therapeutic range and parallel what is known for phenytoin. Control of therapy by measurement of plasma levels of ethotoin is accordingly advocated."}
{"id": "PMID:238783", "title": "Effect of liver failure on the response of ventilation and cerebral criculation to carbon dioxide in man and in the goat.", "content": "1. The acid-base state of arterial blood and cerebrospinal fluid, and the ventilatory response to CO2, were measured in twelve patients with liver disease. The CO2 response was also measured in eight goats before and after the experimental production of liver failure. Arterial PCO2 and pH, cerebral blood flow and the cerebral metabolic rate for oxygen were also measured in four of the goats while they breathed air and various CO2-enriched gas mixtures. 2. Liver failure was accompanied by a respiratory alkalosis in both the patients and in the goats. Decreased PCO2 and increased pH occurred in the cerebrospinal fluid and in the arterial blood of the patients. 3. The slope of the ventilatory response to CO2 was reduced when liver failure was severe, in patients and goats alike. In addition there was a reduction in the extrapolated PCO2 at zero ventilation, even when liver failure was mild. 4. Cerebral blood flow and metabolic rate were consistently reduced in the goats during liver failure. There was also less cerebral vasodilatation and a greater reduction in cerebral metabolism during experimental hypercapnia when these animals were in liver failure. 5. The decreases in the ventilatory and cerebral circulatory responsiveness to CO2 indicate that the brain is less well defended against hypercapnia in liver failure, and these changes are especially unfavourable as cerebral function deteriorates when the PCO2 is increased.", "contents": "Effect of liver failure on the response of ventilation and cerebral criculation to carbon dioxide in man and in the goat. 1. The acid-base state of arterial blood and cerebrospinal fluid, and the ventilatory response to CO2, were measured in twelve patients with liver disease. The CO2 response was also measured in eight goats before and after the experimental production of liver failure. Arterial PCO2 and pH, cerebral blood flow and the cerebral metabolic rate for oxygen were also measured in four of the goats while they breathed air and various CO2-enriched gas mixtures. 2. Liver failure was accompanied by a respiratory alkalosis in both the patients and in the goats. Decreased PCO2 and increased pH occurred in the cerebrospinal fluid and in the arterial blood of the patients. 3. The slope of the ventilatory response to CO2 was reduced when liver failure was severe, in patients and goats alike. In addition there was a reduction in the extrapolated PCO2 at zero ventilation, even when liver failure was mild. 4. Cerebral blood flow and metabolic rate were consistently reduced in the goats during liver failure. There was also less cerebral vasodilatation and a greater reduction in cerebral metabolism during experimental hypercapnia when these animals were in liver failure. 5. The decreases in the ventilatory and cerebral circulatory responsiveness to CO2 indicate that the brain is less well defended against hypercapnia in liver failure, and these changes are especially unfavourable as cerebral function deteriorates when the PCO2 is increased."}
{"id": "PMID:238784", "title": "Analytical subcellular fractionation of human granulocytes with reference to the localization of vitamin B12-binding proteins.", "content": "1. A granulocyte-rich fraction was isolated from blood of a patient with chronic granulocytic leukaemia and from blood of a normal subject and the cells were disrupted in isotonic sucrose. The nuclei were removed by low-speed centrifugation and the post-nuclear supernatant was fractionated by centrifugation on sucrose density gradients. 2. The subcellular organelles in the gradients were detected with marker enzymes by the use of highly sensitive assay techniques. Similar results were obtained with granulocytes from both subjects. 3. Unsaturated vitamin B12-binding proteins were almost exclusively localized to the specific granules. Chromatographic analysis of these proteins showed them to have approximately equal proportions of transcobalamins I and III. Vitamin B12 assayed microbiologically could not be detected in the specific granule fractions.", "contents": "Analytical subcellular fractionation of human granulocytes with reference to the localization of vitamin B12-binding proteins. 1. A granulocyte-rich fraction was isolated from blood of a patient with chronic granulocytic leukaemia and from blood of a normal subject and the cells were disrupted in isotonic sucrose. The nuclei were removed by low-speed centrifugation and the post-nuclear supernatant was fractionated by centrifugation on sucrose density gradients. 2. The subcellular organelles in the gradients were detected with marker enzymes by the use of highly sensitive assay techniques. Similar results were obtained with granulocytes from both subjects. 3. Unsaturated vitamin B12-binding proteins were almost exclusively localized to the specific granules. Chromatographic analysis of these proteins showed them to have approximately equal proportions of transcobalamins I and III. Vitamin B12 assayed microbiologically could not be detected in the specific granule fractions."}
{"id": "PMID:238778", "title": "The influence of cholinoceptor activity on the mitotic rate in the crypts of Lieberk\u00fchn in rat jejunum.", "content": "1. The influence of cholinoceptor stimulation and cholinoceptor blockade on the mitotic rate in epithelial cells lining the crypts of Lieberk\u00fchn in rat jejunum was studied. 2. Cholinoceptor stimulation, either by injection of carbachol or by inhibition of acetylcholinesterase enzymes resulted in an increase in the mitotic rate. This increase in mitotic rate was blocked by tubocurarine, but not by atropine or hexamethonium. Atropine by itself increased the mitotic rate whereas tubocurarine alone or hexamethonium along decreased the mitotic rate. 3. The influence of atropine on crypt cell proliferation appears to involve an adrenergic mechanism since it is blocked by phentolamine.", "contents": "The influence of cholinoceptor activity on the mitotic rate in the crypts of Lieberk\u00fchn in rat jejunum. 1. The influence of cholinoceptor stimulation and cholinoceptor blockade on the mitotic rate in epithelial cells lining the crypts of Lieberk\u00fchn in rat jejunum was studied. 2. Cholinoceptor stimulation, either by injection of carbachol or by inhibition of acetylcholinesterase enzymes resulted in an increase in the mitotic rate. This increase in mitotic rate was blocked by tubocurarine, but not by atropine or hexamethonium. Atropine by itself increased the mitotic rate whereas tubocurarine alone or hexamethonium along decreased the mitotic rate. 3. The influence of atropine on crypt cell proliferation appears to involve an adrenergic mechanism since it is blocked by phentolamine."}
{"id": "PMID:238789", "title": "Calcification of the heart and great vessels.", "content": "Calcification of the heart and great vessels is secondary to those diseases which cause a significant alteration of tissue matrix. Metabolic derangements can cause microscopic calcification of heart muscle, but this has not been demonstrated conclusively roentgenographically. The deposition of calcium may follow a single event or be the result of a longstanding process. The etiology and roentgen appearance of calcium deposition in the various tissues which comprise the heart and great vessels are reveiwed. The common as well as the rare cases are considered; if possible, each entity is demonstrated roentgenographically. In addition, an attempt is made to reciew various points of view, which at times are conflicting. The prognostic importance of cardiac, aortic, or pulmonary arterial calcification is underscored whenever possible.", "contents": "Calcification of the heart and great vessels. Calcification of the heart and great vessels is secondary to those diseases which cause a significant alteration of tissue matrix. Metabolic derangements can cause microscopic calcification of heart muscle, but this has not been demonstrated conclusively roentgenographically. The deposition of calcium may follow a single event or be the result of a longstanding process. The etiology and roentgen appearance of calcium deposition in the various tissues which comprise the heart and great vessels are reveiwed. The common as well as the rare cases are considered; if possible, each entity is demonstrated roentgenographically. In addition, an attempt is made to reciew various points of view, which at times are conflicting. The prognostic importance of cardiac, aortic, or pulmonary arterial calcification is underscored whenever possible."}
{"id": "PMID:238790", "title": "Double-blind trials of clemastine ('Tavegil') in allergic rhinitis.", "content": "Two double-blind randomised trials are reported comparing the effectiveness of the antihistamines, clemastine and chlorpheniramine in comparable doses, in relieving the symptoms of allergic rhinitis. In the first trial, treating 58 adults seen in a general practice, both drugs were prescribed in tablet form; l mg. clemastine b.d. and 4 mg. chlorpheniramine b.d. The second trial was carried out in 42 patients attending a children's E.N.T. out-patient department and the drugs were prescribed as clemastine elixir (0.5 mg. b.d.) or as chlorpheniramine syrup (2 mg. b.d.). Both drugs were effective in providing symptomatic relief in a significant number of patients, and the overall efficacy of clemastine was marginally better than that of chlorpheniramine, especially in the second trial in children. Side-effects were minimal and drowsiness was not a problem.", "contents": "Double-blind trials of clemastine ('Tavegil') in allergic rhinitis. Two double-blind randomised trials are reported comparing the effectiveness of the antihistamines, clemastine and chlorpheniramine in comparable doses, in relieving the symptoms of allergic rhinitis. In the first trial, treating 58 adults seen in a general practice, both drugs were prescribed in tablet form; l mg. clemastine b.d. and 4 mg. chlorpheniramine b.d. The second trial was carried out in 42 patients attending a children's E.N.T. out-patient department and the drugs were prescribed as clemastine elixir (0.5 mg. b.d.) or as chlorpheniramine syrup (2 mg. b.d.). Both drugs were effective in providing symptomatic relief in a significant number of patients, and the overall efficacy of clemastine was marginally better than that of chlorpheniramine, especially in the second trial in children. Side-effects were minimal and drowsiness was not a problem."}
{"id": "PMID:238791", "title": "A preliminary evaluation of pipothiazine palmitate in schizophrenia.", "content": "A preliminary evaluation of pipothiazine palmitate by injection was carried out in 25 schizophrenic patients to assess the therapeutic effectiveness of the drug, probable dosage schedules and intervals between doses, and to observ any undesirable side-effects. A good overall response was obtained in 64% of the patients. The authors suggest that the optimum maintenance dosage is between 50 and 100 mg. given at 4-weekly intervals. Although extra-pyramidal side-effects were high, only 1 patient had to be withdrawn on this account; the symptoms being well-controlled in mostly by procyclidine. Other adverse side-effects were negligible and there was no evidence of adverse biological effects. It is concluded that pipthiazine palmitate has considerable potential in the treatment of schizophrenia and a longer-term study is being conducted.", "contents": "A preliminary evaluation of pipothiazine palmitate in schizophrenia. A preliminary evaluation of pipothiazine palmitate by injection was carried out in 25 schizophrenic patients to assess the therapeutic effectiveness of the drug, probable dosage schedules and intervals between doses, and to observ any undesirable side-effects. A good overall response was obtained in 64% of the patients. The authors suggest that the optimum maintenance dosage is between 50 and 100 mg. given at 4-weekly intervals. Although extra-pyramidal side-effects were high, only 1 patient had to be withdrawn on this account; the symptoms being well-controlled in mostly by procyclidine. Other adverse side-effects were negligible and there was no evidence of adverse biological effects. It is concluded that pipthiazine palmitate has considerable potential in the treatment of schizophrenia and a longer-term study is being conducted."}
{"id": "PMID:238792", "title": "The thymoleptic action of two salts of flurazepam ('Dalmane').", "content": "A double-blind comparison was made of two dose levels (15 and 30 mg.) of the monohydrochloride and dihydrochloride salts of flurazepam ('Dalmane') in 40 hospitalised patients requiring a night-time hypnotic. Each patient in the four drug/dose groups was his own control and took a placebo for 3 nights followed by the active compound for a further 3 nights. On waking each morning a mood state questionnaire was completed. The results indicate that flurazepam is not only an effective hypnotic, but that it has an apparent anxiolytic effect the following morning. Patients report feeling less anxious and more cheerful following drug administration and this result was most noticeable with the 15 mg. monohydrochloride dose.", "contents": "The thymoleptic action of two salts of flurazepam ('Dalmane'). A double-blind comparison was made of two dose levels (15 and 30 mg.) of the monohydrochloride and dihydrochloride salts of flurazepam ('Dalmane') in 40 hospitalised patients requiring a night-time hypnotic. Each patient in the four drug/dose groups was his own control and took a placebo for 3 nights followed by the active compound for a further 3 nights. On waking each morning a mood state questionnaire was completed. The results indicate that flurazepam is not only an effective hypnotic, but that it has an apparent anxiolytic effect the following morning. Patients report feeling less anxious and more cheerful following drug administration and this result was most noticeable with the 15 mg. monohydrochloride dose."}
{"id": "PMID:238794", "title": "The effects of acute severe arterial hypoxemia on the electrocardiogram during exercise.", "content": "Sixteen healthy, active men were studied to determine the effects of severe arterial hypoxemia on the electrocardiograms during exercise. The electrocardiograms were all normal at maximum heart rate while the subject breathed ambient air. During maximal exercise breathing ten percent oxygen (mean arterial oxygen pressure [Po2] of 31 mm Hg), only one of the 16 had ST segment changes suggestive of ischemia. These were not present on a repeated study. The widely held view that systemic hypoxemia causes ischemic changes on the electrocardiogram was not confirmed in this study.", "contents": "The effects of acute severe arterial hypoxemia on the electrocardiogram during exercise. Sixteen healthy, active men were studied to determine the effects of severe arterial hypoxemia on the electrocardiograms during exercise. The electrocardiograms were all normal at maximum heart rate while the subject breathed ambient air. During maximal exercise breathing ten percent oxygen (mean arterial oxygen pressure [Po2] of 31 mm Hg), only one of the 16 had ST segment changes suggestive of ischemia. These were not present on a repeated study. The widely held view that systemic hypoxemia causes ischemic changes on the electrocardiogram was not confirmed in this study."}
{"id": "PMID:238795", "title": "Functional characteristics of the lung in chronic uremia treated by renal dialysis therapy.", "content": "Ventilatory studies and arterial blood gas analyses were performed in 29 patients with chronic renal failure undergoing renal dialysis therapy (RDT). Twenty-three of the 29 had nearly normal pulmonary function, and the accumulation of body water between dialyses did not influence pulmonary function significantly. A trend was observed towards overinflation and air trapping in the presence of normal airway resistance, indicating narrowing of the small airways. Repeated studies over a 16-month period suggest that these patients develop neither chronic obstructive airway disease nor restrictive ventilatory impairment. Six patients had a restrictive ventilatory impairment with a trend to overdistension and air trapping as in the \"normal\" patients. This was observed both early and late in the course of RDT and appeared to be irreversible but not progressive. These patients had suffered from uremic pleuropericarditis and either had serous effusions or residual adhesions.", "contents": "Functional characteristics of the lung in chronic uremia treated by renal dialysis therapy. Ventilatory studies and arterial blood gas analyses were performed in 29 patients with chronic renal failure undergoing renal dialysis therapy (RDT). Twenty-three of the 29 had nearly normal pulmonary function, and the accumulation of body water between dialyses did not influence pulmonary function significantly. A trend was observed towards overinflation and air trapping in the presence of normal airway resistance, indicating narrowing of the small airways. Repeated studies over a 16-month period suggest that these patients develop neither chronic obstructive airway disease nor restrictive ventilatory impairment. Six patients had a restrictive ventilatory impairment with a trend to overdistension and air trapping as in the \"normal\" patients. This was observed both early and late in the course of RDT and appeared to be irreversible but not progressive. These patients had suffered from uremic pleuropericarditis and either had serous effusions or residual adhesions."}
{"id": "PMID:238796", "title": "Direct and vagally mediated chronotropic effects of morphine studied by selective perfusion of the sinus node of awake dogs.", "content": "Two milliliters of a morphine sulfate solution (1 mg/ml) perfused selectively into the sinus node artery of five trained unanesthetized dogs caused an immediate brief sinus tachycardia followed by a delayed but prolonged sinus bradycardia. Beta-receptor blockade was achieved by selective perfusion of propranolol hydrochloride solution (10 mug/ml) into the sinus node artery and did not prevent the initial sinus tachycardia. Selective perfusion of the sinus node with atropine sulfate solution (1 mug/ml), however, did prevent morphine from causing further sinus rate increase. The immediate positive chronotropic action of morphine was thus attributable to a peripherally located vagolytic action. The exact opposite was true with regard to the delayed bradycardia; it was due to a centrally mediated generalized increase in vagal tone regularly elicited by morphine.", "contents": "Direct and vagally mediated chronotropic effects of morphine studied by selective perfusion of the sinus node of awake dogs. Two milliliters of a morphine sulfate solution (1 mg/ml) perfused selectively into the sinus node artery of five trained unanesthetized dogs caused an immediate brief sinus tachycardia followed by a delayed but prolonged sinus bradycardia. Beta-receptor blockade was achieved by selective perfusion of propranolol hydrochloride solution (10 mug/ml) into the sinus node artery and did not prevent the initial sinus tachycardia. Selective perfusion of the sinus node with atropine sulfate solution (1 mug/ml), however, did prevent morphine from causing further sinus rate increase. The immediate positive chronotropic action of morphine was thus attributable to a peripherally located vagolytic action. The exact opposite was true with regard to the delayed bradycardia; it was due to a centrally mediated generalized increase in vagal tone regularly elicited by morphine."}
{"id": "PMID:238799", "title": "Determination of isonicotinic acid hydrazide in serum.", "content": "A method for the determination of isonicotinic acid hydrazide is given. The hydrazide is complexed with cupric ions and condensated with an aromatic aldehyde substituted in ortho-position with a hydroxyl group. The method is adapted to the AutoAnalyzer equipment of first and second generation. Pilot measurements on the pharmacokinetic behaviour of isonicotinic acid hydrazide are presented.", "contents": "Determination of isonicotinic acid hydrazide in serum. A method for the determination of isonicotinic acid hydrazide is given. The hydrazide is complexed with cupric ions and condensated with an aromatic aldehyde substituted in ortho-position with a hydroxyl group. The method is adapted to the AutoAnalyzer equipment of first and second generation. Pilot measurements on the pharmacokinetic behaviour of isonicotinic acid hydrazide are presented."}
{"id": "PMID:238800", "title": "Culture and morphological observations on Trypanosoma melphagium.", "content": "The cultural characteristics of Trypanosoma melophagium of sheep were studied. Aspects investigated were size of the inoculum and population growth in Modified Monophasic Medium for Trypanosomes (MMMT), population growth in Medium 199 with 10% inactivated calf serum containing 5, 10, and 15% hemolyzed defibrinated rabbit blood (199-CS-5, 199--CS-10, 199-CS-15) at 27 degrees C, effects on population growth of temperature and hydrogen ion concentration in MMMT, and morphology and morphometrics of the developmental stages found under different experimental conditions. The best growth occurred in medium MMMT at 30 degrees, C, pH 7.25. Temperature seemed to be a critical factor for differentiation of epimastigotes to trypomastigotes. Statistically significant differences were found between the trypomastigotes in MMMT and 199--cs-5 at 37 degrees C on day 4 of incubation for the following measurements: PK (distance from posterior end to kinetoplast), KN (from kinetoplast to middle of nucleus), PN (from posterior end to middle of nucleus), and nuclear and kinetoplastic indices. The trypomastigotes formed in both media were much smaller in size than the blood forms reported by Hoare (1972).", "contents": "Culture and morphological observations on Trypanosoma melphagium. The cultural characteristics of Trypanosoma melophagium of sheep were studied. Aspects investigated were size of the inoculum and population growth in Modified Monophasic Medium for Trypanosomes (MMMT), population growth in Medium 199 with 10% inactivated calf serum containing 5, 10, and 15% hemolyzed defibrinated rabbit blood (199-CS-5, 199--CS-10, 199-CS-15) at 27 degrees C, effects on population growth of temperature and hydrogen ion concentration in MMMT, and morphology and morphometrics of the developmental stages found under different experimental conditions. The best growth occurred in medium MMMT at 30 degrees, C, pH 7.25. Temperature seemed to be a critical factor for differentiation of epimastigotes to trypomastigotes. Statistically significant differences were found between the trypomastigotes in MMMT and 199--cs-5 at 37 degrees C on day 4 of incubation for the following measurements: PK (distance from posterior end to kinetoplast), KN (from kinetoplast to middle of nucleus), PN (from posterior end to middle of nucleus), and nuclear and kinetoplastic indices. The trypomastigotes formed in both media were much smaller in size than the blood forms reported by Hoare (1972)."}
{"id": "PMID:238802", "title": "DNA sequence organization in the genomes of five marine invertebrates.", "content": "The arrangement of repetitive and non-repetitive sequence was studied in the genomic DNA of the oyster (Crassostrea virginica), the surf clam (Spisula solidissima), the horseshoe crab (Limulus polyphemus), a nemertean worm (Cerebratulus lacteus) and a jelly-fish (Aurelia aurita). Except for the jellyfish these animals belong to the protostomial branch of animal evolution, for which little information regarding DNA sequence organization has previously been available. The reassociation kinetics of short (250-300 nucleotide) and long (2,000-3,000 nucleotide) DNA fragments was studied by the hydroxyapatite method. It was shown that in each case a major fraction of the DNA consists of single copy sequences less than about 3,000 nucleotides in length, interspersed with short repetitive sequences. The lengths of the repetitive sequences were estimated by optical hyperchromicity and S1 nuclease measurements made on renaturation products. All the genomes studied include a prominent fraction of interspersed repetitive sequences about 300 nucleotides in length, as well as longer repetitive sequence regions.", "contents": "DNA sequence organization in the genomes of five marine invertebrates. The arrangement of repetitive and non-repetitive sequence was studied in the genomic DNA of the oyster (Crassostrea virginica), the surf clam (Spisula solidissima), the horseshoe crab (Limulus polyphemus), a nemertean worm (Cerebratulus lacteus) and a jelly-fish (Aurelia aurita). Except for the jellyfish these animals belong to the protostomial branch of animal evolution, for which little information regarding DNA sequence organization has previously been available. The reassociation kinetics of short (250-300 nucleotide) and long (2,000-3,000 nucleotide) DNA fragments was studied by the hydroxyapatite method. It was shown that in each case a major fraction of the DNA consists of single copy sequences less than about 3,000 nucleotides in length, interspersed with short repetitive sequences. The lengths of the repetitive sequences were estimated by optical hyperchromicity and S1 nuclease measurements made on renaturation products. All the genomes studied include a prominent fraction of interspersed repetitive sequences about 300 nucleotides in length, as well as longer repetitive sequence regions."}
{"id": "PMID:238803", "title": "Comparative aspects of DNA organization in Metazoa.", "content": "Data on sequence organization in metazoa are reviewed and tabulated. It is shown that the features of sequence organization previously observed in Xenopus DNA are extremely widespread. At least 70% of DNA fragments 2,000-3,000 nucleotides long contain both single copy and repetitive sequence in all the organisms examined except Drosophila.", "contents": "Comparative aspects of DNA organization in Metazoa. Data on sequence organization in metazoa are reviewed and tabulated. It is shown that the features of sequence organization previously observed in Xenopus DNA are extremely widespread. At least 70% of DNA fragments 2,000-3,000 nucleotides long contain both single copy and repetitive sequence in all the organisms examined except Drosophila."}
{"id": "PMID:238804", "title": "Energetic aspects of transport of ADP and ATP through the mitochondrial membrane.", "content": "Evidence from various sources demonstrates that the release of ATP in exchange for the entry of ADP across the mitochondrial membrane is an active process requiring energy. The necessary energy may be derived from the same source of energy as that used for oxidative phosphorylation. The following results will be discussed:--(1) The exchange is asymmetric with respect to the specificity of ADP and ATP in 'energized' mitochondria. From the outside ADP is much preferred to ATP, but from the inside both exchange with equal specificity. This asymmetry is abolished by de-energization of the membrane. (2) The ADP-ATP exchange is about 50% electrogenic: about half the ATP released against ADP is protonated. The excess of negatively charged ATP might prevent ADP from entering mitochondria against a membrane potential. (3) The ratio of ATP to ADP across the inner mitochondrial membrane is higher outside than inside only in the energized state. Variation of the ATP/ADP ratio maintains this difference. (4) The ADP/ATP ratio apparently varies with changes in the membrane potential as measured by Rb+-distribution. The correlation factor between deltaE changes and this ratio is 0.5, in agreement with predictions from proton-stoichiometry measurements. The deltapH does not significantly change the distribution ratio. (5) By following the P/O ratio, one can show that energy derived from expelling ATP against the ADP/ATP gradient lowers the amount of ATP synthesis. The P/O ratio is lowered as the imbalance of ATP to ADP increases. (6) The energy difference of the phosphorylation potential of ATP is calculated by various methods to be about 8-12 kJ, depending on the conditions. This free energy is the result of the 'active' transport which corresponds to the release of ATP outside the mitochondria. (7) In vivo studies on the distribution of ADP and ATP inside and outside the mitochondria in liver show a corresponding ratio difference of about 15 as predicted from the in vitro studies.", "contents": "Energetic aspects of transport of ADP and ATP through the mitochondrial membrane. Evidence from various sources demonstrates that the release of ATP in exchange for the entry of ADP across the mitochondrial membrane is an active process requiring energy. The necessary energy may be derived from the same source of energy as that used for oxidative phosphorylation. The following results will be discussed:--(1) The exchange is asymmetric with respect to the specificity of ADP and ATP in 'energized' mitochondria. From the outside ADP is much preferred to ATP, but from the inside both exchange with equal specificity. This asymmetry is abolished by de-energization of the membrane. (2) The ADP-ATP exchange is about 50% electrogenic: about half the ATP released against ADP is protonated. The excess of negatively charged ATP might prevent ADP from entering mitochondria against a membrane potential. (3) The ratio of ATP to ADP across the inner mitochondrial membrane is higher outside than inside only in the energized state. Variation of the ATP/ADP ratio maintains this difference. (4) The ADP/ATP ratio apparently varies with changes in the membrane potential as measured by Rb+-distribution. The correlation factor between deltaE changes and this ratio is 0.5, in agreement with predictions from proton-stoichiometry measurements. The deltapH does not significantly change the distribution ratio. (5) By following the P/O ratio, one can show that energy derived from expelling ATP against the ADP/ATP gradient lowers the amount of ATP synthesis. The P/O ratio is lowered as the imbalance of ATP to ADP increases. (6) The energy difference of the phosphorylation potential of ATP is calculated by various methods to be about 8-12 kJ, depending on the conditions. This free energy is the result of the 'active' transport which corresponds to the release of ATP outside the mitochondria. (7) In vivo studies on the distribution of ADP and ATP inside and outside the mitochondria in liver show a corresponding ratio difference of about 15 as predicted from the in vitro studies."}
{"id": "PMID:238805", "title": "Bioluminescence: from chemical bonds to photons.", "content": "The biological transformation of chemical to photic energy involves an enzyme-mediated chemiluminescent reaction, in which one of the products exists in an electronically excited state, emitting a photon as it returns to the ground state. The colour of bioluminescence differs in different organisms, ranging from the deep blue (460 nm) of certain crustacea, through the bluish green (490 nm) of some bacteria, the green (530 nm) of mushrooms to the red (about 600 nm) of the railroad worm. In one case, energy transfer has been demonstrated from the enzyme system to material that emits light with a longer wavelength. The energies involved range from about 165 to 250 kJ/einstein (40 to 60 kcal/einstein). Boyle first showed that air was involved in bioluminescence in 1668 in his experiments with an air pump. Over the past 100 years, it has become clear that most if not all bioluminescent systems require molecular oxygen. The recent isolation and characterization of an oxygen-containing (peroxide) enzyme intermediate from the bacterial system is described and a reaction mechanism is postulated. This scheme is compared with other hypothetical mechanisms, in particular those involving a four-membered ring intermediate, a dioxetane, in which the simultaneous cleavage of two bonds leaves one product in an excited state. I shall discuss the special role of luciferases in bioluminescence, especially in flashing mechanisms involving 'precharged' intermediates.", "contents": "Bioluminescence: from chemical bonds to photons. The biological transformation of chemical to photic energy involves an enzyme-mediated chemiluminescent reaction, in which one of the products exists in an electronically excited state, emitting a photon as it returns to the ground state. The colour of bioluminescence differs in different organisms, ranging from the deep blue (460 nm) of certain crustacea, through the bluish green (490 nm) of some bacteria, the green (530 nm) of mushrooms to the red (about 600 nm) of the railroad worm. In one case, energy transfer has been demonstrated from the enzyme system to material that emits light with a longer wavelength. The energies involved range from about 165 to 250 kJ/einstein (40 to 60 kcal/einstein). Boyle first showed that air was involved in bioluminescence in 1668 in his experiments with an air pump. Over the past 100 years, it has become clear that most if not all bioluminescent systems require molecular oxygen. The recent isolation and characterization of an oxygen-containing (peroxide) enzyme intermediate from the bacterial system is described and a reaction mechanism is postulated. This scheme is compared with other hypothetical mechanisms, in particular those involving a four-membered ring intermediate, a dioxetane, in which the simultaneous cleavage of two bonds leaves one product in an excited state. I shall discuss the special role of luciferases in bioluminescence, especially in flashing mechanisms involving 'precharged' intermediates."}
{"id": "PMID:238806", "title": "The purple membrane of Halobacterium halobium: a new system for light energy conversion.", "content": "Patches of a distinctly different structure from the rest of the cell membrane occur in Halobacterium halobium. The isolated patches are called the purple membrane. It derives its colour from a retinal-protein complex, bacteriorhodopsin, which is the only protein species in this membrane serving a phototransducing function. Light energy is converted by a photochemical cycle going on continuously under illumination and accompanied by a cyclic release and uptake of protons. In the intact cell, this cycle operates as a vectorial process and therefore builds up an electrochemical gradient across the cell membrane conserving part of the absorbed light energy. The cell apparently uses this electrochemical gradient for the synthesis of ATP. Photophosphorylation is shown to be insensitive to cyanide but sensitive to dicyclohexylcarbodiimide (DCCD) and uncouplers. The concentration of ATP and the pH are tightly coupled but can be uncoupled by DCCD. Bacteriorhodopsin, as a light-driven proton pump, can then be studied in the cell as an isolated process. Quantitation of light energy conversion is possible by the indirect method of inhibition of respiration by light and the comparison of the number of absorbed quanta which prevent consumption of one molecule of oxygen.", "contents": "The purple membrane of Halobacterium halobium: a new system for light energy conversion. Patches of a distinctly different structure from the rest of the cell membrane occur in Halobacterium halobium. The isolated patches are called the purple membrane. It derives its colour from a retinal-protein complex, bacteriorhodopsin, which is the only protein species in this membrane serving a phototransducing function. Light energy is converted by a photochemical cycle going on continuously under illumination and accompanied by a cyclic release and uptake of protons. In the intact cell, this cycle operates as a vectorial process and therefore builds up an electrochemical gradient across the cell membrane conserving part of the absorbed light energy. The cell apparently uses this electrochemical gradient for the synthesis of ATP. Photophosphorylation is shown to be insensitive to cyanide but sensitive to dicyclohexylcarbodiimide (DCCD) and uncouplers. The concentration of ATP and the pH are tightly coupled but can be uncoupled by DCCD. Bacteriorhodopsin, as a light-driven proton pump, can then be studied in the cell as an isolated process. Quantitation of light energy conversion is possible by the indirect method of inhibition of respiration by light and the comparison of the number of absorbed quanta which prevent consumption of one molecule of oxygen."}
{"id": "PMID:238807", "title": "Energy transfer in mitochondrial synthesis of ATP; a survey.", "content": "The energy transduction in mitochondria, with its principal agent ATP, still represents a major challenge for biological research. In general, the energy transduction process is divided into three sections: (1) the redox processes; (2) a conservation of intermediary energy forms; (3) synthesis of ATP. All three processes are linked to the membrane and are, therefore, as difficult to resolve as are processes linked to other biomembranes. It is probable that the electron transport system is constructed in such a way as to provide energy for synthesis of ATP and related processes. Important for this function is the transversal distribution of these components across the membrane, facilitating generation of membrane potential by electron or proton transfer. The exact composition of the respiratory chain is not yet known, in particular with respect to iron-sulphur proteins. Progress is achieved by defining single species of the respiratory chain, subunit composition, amino acid sequences and genetic derivation from intra- or extra-mitochondrial translation. Energy generated by oxidation can be trapped before ATP is formed by a number of reactions, in particular reversed electron transport, energy-dependent transhydrogenation and uptake of anions or cations into the mitochondria. The latter reaction is of major importance for understanding the intermediate energy form, as it appears to use energy most directly and be driven mainly by membrane potential or proton gradient across the membrane. The formation of ATP is a major problem hindering elucidation of the mechanism of oxidative phosphorylation. The mechanism of this enzymic process is not yet understood although the enzymes have been isolated and the subunits have been defined. Most probably, a concerted reaction between ADP and phosphate, driven by some conformational transition of the complex, leads to the formation of ATP. Release of ATP from a hydrophobic to hydrophilic environment may consume most of the energy.", "contents": "Energy transfer in mitochondrial synthesis of ATP; a survey. The energy transduction in mitochondria, with its principal agent ATP, still represents a major challenge for biological research. In general, the energy transduction process is divided into three sections: (1) the redox processes; (2) a conservation of intermediary energy forms; (3) synthesis of ATP. All three processes are linked to the membrane and are, therefore, as difficult to resolve as are processes linked to other biomembranes. It is probable that the electron transport system is constructed in such a way as to provide energy for synthesis of ATP and related processes. Important for this function is the transversal distribution of these components across the membrane, facilitating generation of membrane potential by electron or proton transfer. The exact composition of the respiratory chain is not yet known, in particular with respect to iron-sulphur proteins. Progress is achieved by defining single species of the respiratory chain, subunit composition, amino acid sequences and genetic derivation from intra- or extra-mitochondrial translation. Energy generated by oxidation can be trapped before ATP is formed by a number of reactions, in particular reversed electron transport, energy-dependent transhydrogenation and uptake of anions or cations into the mitochondria. The latter reaction is of major importance for understanding the intermediate energy form, as it appears to use energy most directly and be driven mainly by membrane potential or proton gradient across the membrane. The formation of ATP is a major problem hindering elucidation of the mechanism of oxidative phosphorylation. The mechanism of this enzymic process is not yet understood although the enzymes have been isolated and the subunits have been defined. Most probably, a concerted reaction between ADP and phosphate, driven by some conformational transition of the complex, leads to the formation of ATP. Release of ATP from a hydrophobic to hydrophilic environment may consume most of the energy."}
{"id": "PMID:238808", "title": "The active transport of carbohydrates by Escherichia coli.", "content": "The active transport of carbohydrates by Escherichia coli is discussed with particular reference to (1) identification of an uptake process as 'active transport', (2) nature and control of transport proteins, and (3) mechanisms of energy transduction. (1) The use of substrate analogues, of mutants blocked in metabolism and of subcellular vesicles in the isolation of the transport process from interference by subsequent metabolic reactions is described. Criteria are outlined for establishing that the solute is taken up against a concentration gradient and that this is energy-dependent. Three types of poisons for energy systems that act primarily on respiration, on ATP formation and as uncoupling ('proton conducting') agents are considered. (2) Methods are described for the selection of mutants impaired in the active uptake of specific carbohydrates. (3) Results show that the uptake of galactose, D-fucose and arabinose by appropriate strains of E. coli is inducible, specific and accompanied by proton uptake. Such and other data support a model based on a chemiosmotic theory of active transport.", "contents": "The active transport of carbohydrates by Escherichia coli. The active transport of carbohydrates by Escherichia coli is discussed with particular reference to (1) identification of an uptake process as 'active transport', (2) nature and control of transport proteins, and (3) mechanisms of energy transduction. (1) The use of substrate analogues, of mutants blocked in metabolism and of subcellular vesicles in the isolation of the transport process from interference by subsequent metabolic reactions is described. Criteria are outlined for establishing that the solute is taken up against a concentration gradient and that this is energy-dependent. Three types of poisons for energy systems that act primarily on respiration, on ATP formation and as uncoupling ('proton conducting') agents are considered. (2) Methods are described for the selection of mutants impaired in the active uptake of specific carbohydrates. (3) Results show that the uptake of galactose, D-fucose and arabinose by appropriate strains of E. coli is inducible, specific and accompanied by proton uptake. Such and other data support a model based on a chemiosmotic theory of active transport."}
{"id": "PMID:238809", "title": "Chloroplasts.", "content": "Illuminated chloroplast fragments, which can convert light into chemical energy (NADPH2 and ATP), contain a number of soluble and insoluble electron carriers that have been arranged, on the basis of their redox potentials and on kinetic and other evidence, in sequences (analogous to those in mitochondria) to describe the events involved in the light reactions of photosynthesis. Fractionation of chloroplasts allows separation of two light-dependent partial reactions: the evolution of oxygen and the reduction of pyridine nucleotide, accompanied by ATP synthesis. The stoichiometry of the latter reaction is still uncertain. Chloroplasts contain a directional proton-translocating ATPase (CF1) needed for the phosphorylation of ADP in the light. The CF1 also catalyses synthesis of ATP from ADP. When a pH gradient is applied in the dark across the phosphorylating membranes, the amount of ATP synthesized is related to both the change in pH and the electrical potential. During its catalytic activity, the CF1 protein undergoes reversible conformational changes, but this is not the source of the driving force for ATP synthesis.", "contents": "Chloroplasts. Illuminated chloroplast fragments, which can convert light into chemical energy (NADPH2 and ATP), contain a number of soluble and insoluble electron carriers that have been arranged, on the basis of their redox potentials and on kinetic and other evidence, in sequences (analogous to those in mitochondria) to describe the events involved in the light reactions of photosynthesis. Fractionation of chloroplasts allows separation of two light-dependent partial reactions: the evolution of oxygen and the reduction of pyridine nucleotide, accompanied by ATP synthesis. The stoichiometry of the latter reaction is still uncertain. Chloroplasts contain a directional proton-translocating ATPase (CF1) needed for the phosphorylation of ADP in the light. The CF1 also catalyses synthesis of ATP from ADP. When a pH gradient is applied in the dark across the phosphorylating membranes, the amount of ATP synthesized is related to both the change in pH and the electrical potential. During its catalytic activity, the CF1 protein undergoes reversible conformational changes, but this is not the source of the driving force for ATP synthesis."}
{"id": "PMID:238810", "title": "A double-blind comparison of loxitane--loxapine succinate and trifluoperazine hydrochloride in chronic schizophrenic patients.", "content": "Therapeutic efficacy and safety of loxapine succinate (LOX) and trifluoperazine hydrochloride were compared by means of a controlled, double-blind study involving 49 chronic schizophrenic inpatients. The data indicated that LOX in dosages ranging from 40 - 65 mg/day, (usually administered on a b.i.d. schedule) had demonstrable anti-psychotic activity in 14 of 25 chronic schizophrenic patients (56%), while TFP treatment in appropriate dosage showed a similar activity in 9 of 23 patients (39%). Both LOX and TFP displayed essentially the same profile and incidence of side effects. Clinical laboratory abnormalities were minor. On the basis of this study, and in comparison with trifluoperazine, it appears that loxapine is an efficacious and essentially safe medication, suitable for the treatment of chronic schizophrenia.", "contents": "A double-blind comparison of loxitane--loxapine succinate and trifluoperazine hydrochloride in chronic schizophrenic patients. Therapeutic efficacy and safety of loxapine succinate (LOX) and trifluoperazine hydrochloride were compared by means of a controlled, double-blind study involving 49 chronic schizophrenic inpatients. The data indicated that LOX in dosages ranging from 40 - 65 mg/day, (usually administered on a b.i.d. schedule) had demonstrable anti-psychotic activity in 14 of 25 chronic schizophrenic patients (56%), while TFP treatment in appropriate dosage showed a similar activity in 9 of 23 patients (39%). Both LOX and TFP displayed essentially the same profile and incidence of side effects. Clinical laboratory abnormalities were minor. On the basis of this study, and in comparison with trifluoperazine, it appears that loxapine is an efficacious and essentially safe medication, suitable for the treatment of chronic schizophrenia."}
{"id": "PMID:238812", "title": "Pharmacokinetic study of a peripheral analgesic, floctafenin, in man, mouse, rat, and dog.", "content": "The pharmacokinetics of floctafenin has been studied in man, mice, rats, and dogs at pharmacological doses. Its absorption, which is exclusively intestinal, is good in man and rodents, but only partial in dogs. Its high plasma clearance rate is primarily due to hepatic hydrolysis to floctafenic acid, which is the main circulating product almost immediately following hydrolysis to floctafenic acid, which is the main circulating product almost immediately following iv administration. The compound binds to two sets of binding sites in animal serum and human plasma with affinity constants of 10(7) M-1 and 10(5) M-1 at 4 degrees C in all species except the dog, where binding is weaker. This binding has been shown to be solely accounted for by albumin. Floctafenin, less protein-bound than floctafenic acid, diffuses more widely into tissues, but very low quantities of the ester and virtually negligible quantities of the acid cross the blood-brain barrier, indicating that their analgesic activity is exclusively peripheral. The elimination of floctafenin and its metabolites is practically complete in 24 hr. The main excretory route is via the bile, biliary excretion being largely predominant in dogs and rats, and somewhat less so in man and mice. There is no enterohepatic cycle of note. The main metabolite in both bile and urine is floctafenic acid. A secondary metabolic pathway, common to all species, leads, by hydroxylation in the postion para to the anthranilic nitrogen, to the corresponding phenols. All products in man and rats are excreted primarily in the form of ether and/or ester O-glucuronides.", "contents": "Pharmacokinetic study of a peripheral analgesic, floctafenin, in man, mouse, rat, and dog. The pharmacokinetics of floctafenin has been studied in man, mice, rats, and dogs at pharmacological doses. Its absorption, which is exclusively intestinal, is good in man and rodents, but only partial in dogs. Its high plasma clearance rate is primarily due to hepatic hydrolysis to floctafenic acid, which is the main circulating product almost immediately following hydrolysis to floctafenic acid, which is the main circulating product almost immediately following iv administration. The compound binds to two sets of binding sites in animal serum and human plasma with affinity constants of 10(7) M-1 and 10(5) M-1 at 4 degrees C in all species except the dog, where binding is weaker. This binding has been shown to be solely accounted for by albumin. Floctafenin, less protein-bound than floctafenic acid, diffuses more widely into tissues, but very low quantities of the ester and virtually negligible quantities of the acid cross the blood-brain barrier, indicating that their analgesic activity is exclusively peripheral. The elimination of floctafenin and its metabolites is practically complete in 24 hr. The main excretory route is via the bile, biliary excretion being largely predominant in dogs and rats, and somewhat less so in man and mice. There is no enterohepatic cycle of note. The main metabolite in both bile and urine is floctafenic acid. A secondary metabolic pathway, common to all species, leads, by hydroxylation in the postion para to the anthranilic nitrogen, to the corresponding phenols. All products in man and rats are excreted primarily in the form of ether and/or ester O-glucuronides."}
{"id": "PMID:238814", "title": "Metabolism of propionyl erythromycin lauryl sulfate. I. Fate of the propionyl erythromycin moiety in the rat.", "content": "The absorption, excretion, and metabolism of propionyl erythromycin (PE) has been studied in the rat. The major routes of metabolism of PE are ester hydrolysis and N-demethylation. The rates of these two reactions have been examined in vivo using radiolabeled PE. The plasma half-life of the ester is 5.5 hr. The correlation of blood levels of radioactivity with 14CO2 production indicates that the ester is continually hydrolyzed after absorption. The half-life of the dimethyl-amino moiety of the desosamine sugar is estimated at 1.5 hr. This relatively short half-life compared to that of the ester is supported by the fact that at 3.5 hr after dosing there is twice as much desmethyl-PE in plasma as PE. After oral administration of either 14C-PE or 14C-erythromycin, 70% of the radioactivity is absorbed in 6 hr. The major route of excretion is via bile. Approximatley 40% of the absorbed dose is excreted in bile in the first 6 hr after dosing. Tissue levels of radioactivity after administration of 14C-erythromycin or 14C-PE indicate that PE or a metabolite accumulates in the tissue during chronic dosing, whereas erythromycin-related levels are similar after single or multiple doses.", "contents": "Metabolism of propionyl erythromycin lauryl sulfate. I. Fate of the propionyl erythromycin moiety in the rat. The absorption, excretion, and metabolism of propionyl erythromycin (PE) has been studied in the rat. The major routes of metabolism of PE are ester hydrolysis and N-demethylation. The rates of these two reactions have been examined in vivo using radiolabeled PE. The plasma half-life of the ester is 5.5 hr. The correlation of blood levels of radioactivity with 14CO2 production indicates that the ester is continually hydrolyzed after absorption. The half-life of the dimethyl-amino moiety of the desosamine sugar is estimated at 1.5 hr. This relatively short half-life compared to that of the ester is supported by the fact that at 3.5 hr after dosing there is twice as much desmethyl-PE in plasma as PE. After oral administration of either 14C-PE or 14C-erythromycin, 70% of the radioactivity is absorbed in 6 hr. The major route of excretion is via bile. Approximatley 40% of the absorbed dose is excreted in bile in the first 6 hr after dosing. Tissue levels of radioactivity after administration of 14C-erythromycin or 14C-PE indicate that PE or a metabolite accumulates in the tissue during chronic dosing, whereas erythromycin-related levels are similar after single or multiple doses."}
{"id": "PMID:238813", "title": "Protection by lead nitrate against carbon tetrachloride hepatotoxicity.", "content": "Pretreatment with lead nitrate of rats intoxicated with CCl4 exerted a significant protective effect against several damaging effects of the haloalkane. Liver microsomal lipid peroxidation, one of the earliest phenomena in CCl4 intoxication, was clearly inhibited by pretreating the rats with lead. The heavy metal also ameliorated the polyribosomal disaggregation caused by CCl4. Fatty infiltration in the liver, measured by the triglyceride content in the organ, was less pronounced in CCl4-poisoned rats pretreated with lead than in animals treated with the haloalkane alone. Lipid metabolism was also studied by means of Triton WR 1339-induced hypertriglyceridemia to examine the state of triglyceride secretion from liver into plasma; the higher level of plasma triglyceride in the lead-pretreated rats further strengthened the results obtained on the secretion experiments. Finally, CCl4-induced liver necrosis, as measured by serum transaminases and histological examination, was partially prevented by lead. The mechanism by which lead, an inhibitor of the drug-metabolizing enzyme system, interferes with CCl4 intoxication, is disccused.", "contents": "Protection by lead nitrate against carbon tetrachloride hepatotoxicity. Pretreatment with lead nitrate of rats intoxicated with CCl4 exerted a significant protective effect against several damaging effects of the haloalkane. Liver microsomal lipid peroxidation, one of the earliest phenomena in CCl4 intoxication, was clearly inhibited by pretreating the rats with lead. The heavy metal also ameliorated the polyribosomal disaggregation caused by CCl4. Fatty infiltration in the liver, measured by the triglyceride content in the organ, was less pronounced in CCl4-poisoned rats pretreated with lead than in animals treated with the haloalkane alone. Lipid metabolism was also studied by means of Triton WR 1339-induced hypertriglyceridemia to examine the state of triglyceride secretion from liver into plasma; the higher level of plasma triglyceride in the lead-pretreated rats further strengthened the results obtained on the secretion experiments. Finally, CCl4-induced liver necrosis, as measured by serum transaminases and histological examination, was partially prevented by lead. The mechanism by which lead, an inhibitor of the drug-metabolizing enzyme system, interferes with CCl4 intoxication, is disccused."}
{"id": "PMID:238815", "title": "Metabolism of propionyl erythromycin lauryl sulfate. II. Fate of the lauryl sulfate moiety in the rat and man.", "content": "The absorption, excretion, and metabolism of [1-14C]lauryl sulfate as either the sodium or propionyl erythromycin salt has been studied in the rat and man. In the rat 88% of the radiolabel from propionyl erythromycin [1-14C]lauryl sulfate was excreted in the urine in the 24-hr period following a single oral dose. More than 95% of the radiolabel was excreted as the metabolite butyric acid 4-sulfate. This metabolite was shown to be derived from carbons 1-4 of the lauryl sulfate moiety. There was no evidence of sulfate cleavage in the rat. In man 51-59% of the administered ratioactivity was recovered in the urine. The major excretion product was butyric acid 4-sulfate accounting for approximately 95% of urinary radioactivity. The remainder was unchanged lauryl sulfate. A significant portion of the radiolabeled propionyl erythromycin lauryl sulfate was converted to 14CO2 indicating that the sulfate linkage was cleaved. A minimum value of 9-16% of the dose was metabolized in this manner.", "contents": "Metabolism of propionyl erythromycin lauryl sulfate. II. Fate of the lauryl sulfate moiety in the rat and man. The absorption, excretion, and metabolism of [1-14C]lauryl sulfate as either the sodium or propionyl erythromycin salt has been studied in the rat and man. In the rat 88% of the radiolabel from propionyl erythromycin [1-14C]lauryl sulfate was excreted in the urine in the 24-hr period following a single oral dose. More than 95% of the radiolabel was excreted as the metabolite butyric acid 4-sulfate. This metabolite was shown to be derived from carbons 1-4 of the lauryl sulfate moiety. There was no evidence of sulfate cleavage in the rat. In man 51-59% of the administered ratioactivity was recovered in the urine. The major excretion product was butyric acid 4-sulfate accounting for approximately 95% of urinary radioactivity. The remainder was unchanged lauryl sulfate. A significant portion of the radiolabeled propionyl erythromycin lauryl sulfate was converted to 14CO2 indicating that the sulfate linkage was cleaved. A minimum value of 9-16% of the dose was metabolized in this manner."}
{"id": "PMID:238817", "title": "Excretion and stereoselective biotransformations of dl-, d- and l-norgestrel in women.", "content": "Excretion data and urinary metabolite patterns of di-, d-, and l-norgestrel were obtained from women who received a single, oral 1.5-mg dose of 14C-labeled racemic norgestrel (Ng) or one of its enantiomers. The average percentage of administered radioactivity +/- SD recovered in the urine after 7 days was 58.1 +/- 7.9% for dl-Ng, 44.8 +/- 8.9% for d-Ng, and 63.6 +/- 15.1% for l-Ng; in feces it was 23.4 +/- 7.7% (dl-Ng), 31.6 +/- 8.2% (d-Ng), and 24.8 +/- 10.7% (l-Ng). Different metabolite patterns were observed for each enantiomer in urine, and the pattern for the racemate appeared to be an approximate composite of the metabolite patterns of the two enantiomers. These differences in the metabolite pattern result from stereoselective transformations; notably 16 beta-hydroxylation of l-Ng and ring A reduction of d-Ng. Other stereoselective pathways noted were: 16 alpha- and 1 beta-hydroxylation as well as D-homoannulation of l-Ng and sulfate conjugation of l-16 beta-hydroxynorgestrel; 2 alpha-hydroxylation of d-Ng, formation of a labile neutral, polar compound which contained the norgestrel moiety in the d-form, and formation of a glucuronide of d-16 beta-hydroxynorgestre. The formation of phenolic derivatives occurred to a very minor degree from transformations of the biologically inactive l-enantiomer. With d-norgestrel, this formation occurred to an even lesser extent, if at all.", "contents": "Excretion and stereoselective biotransformations of dl-, d- and l-norgestrel in women. Excretion data and urinary metabolite patterns of di-, d-, and l-norgestrel were obtained from women who received a single, oral 1.5-mg dose of 14C-labeled racemic norgestrel (Ng) or one of its enantiomers. The average percentage of administered radioactivity +/- SD recovered in the urine after 7 days was 58.1 +/- 7.9% for dl-Ng, 44.8 +/- 8.9% for d-Ng, and 63.6 +/- 15.1% for l-Ng; in feces it was 23.4 +/- 7.7% (dl-Ng), 31.6 +/- 8.2% (d-Ng), and 24.8 +/- 10.7% (l-Ng). Different metabolite patterns were observed for each enantiomer in urine, and the pattern for the racemate appeared to be an approximate composite of the metabolite patterns of the two enantiomers. These differences in the metabolite pattern result from stereoselective transformations; notably 16 beta-hydroxylation of l-Ng and ring A reduction of d-Ng. Other stereoselective pathways noted were: 16 alpha- and 1 beta-hydroxylation as well as D-homoannulation of l-Ng and sulfate conjugation of l-16 beta-hydroxynorgestrel; 2 alpha-hydroxylation of d-Ng, formation of a labile neutral, polar compound which contained the norgestrel moiety in the d-form, and formation of a glucuronide of d-16 beta-hydroxynorgestre. The formation of phenolic derivatives occurred to a very minor degree from transformations of the biologically inactive l-enantiomer. With d-norgestrel, this formation occurred to an even lesser extent, if at all."}
{"id": "PMID:238816", "title": "Metabolism of p-(cyclopropylcarbonyl)phenylacetic acid (SQ 20,650). Species Differences.", "content": "The metabolism of p-(cyclopropylcarbonyl)phenyl[14C]acetic acid (I-14C), a nonsteroidal anti-inflammatory agent, has been studied in rats, dogs, and monkeys. Animals were given single intravenous or oral doses of 5 and 50 mg of I-14C/kg. In all cases, 72-88% of the administered dose was excreted in urine, with most of the radioactivity appearing within 24 hr after dosing; less than 11% was found in feces. The half-life (t1/2) of radioactivity in monkey or dog plasma was 1 and 5 hr. respectively, after the oral or intravenous administration of a 5-mg dose of I-14C per kg. At 50 mg/kg, these half-lives increased to 3.5 and 7.7 hr. respectively. More than 90% of the radioactivity in plasma of both species was associated with unchanged drug. Species differences exist in the biotransformation of I. Rat urine contained 93-97% I; 2-6% (alpha-cyclopropyl-alpha-hydroxy-p-tolyl)acetic acid (II); and approximately 1% as conjugates. Monkey urine contained I-glucuronide (88%) and unconjugated II (7-10%). In the dog, I-taurine accounted for 27% of the radioactivity found in urine; II and its taurine conjugate accounted for 20 and 30%, respectively; a small quantity of II-glycine (3%) was also detected. There are three minor metabolites that have not been identified. Metabolite II isolated from dog urine was shown to be dextrorotatory.", "contents": "Metabolism of p-(cyclopropylcarbonyl)phenylacetic acid (SQ 20,650). Species Differences. The metabolism of p-(cyclopropylcarbonyl)phenyl[14C]acetic acid (I-14C), a nonsteroidal anti-inflammatory agent, has been studied in rats, dogs, and monkeys. Animals were given single intravenous or oral doses of 5 and 50 mg of I-14C/kg. In all cases, 72-88% of the administered dose was excreted in urine, with most of the radioactivity appearing within 24 hr after dosing; less than 11% was found in feces. The half-life (t1/2) of radioactivity in monkey or dog plasma was 1 and 5 hr. respectively, after the oral or intravenous administration of a 5-mg dose of I-14C per kg. At 50 mg/kg, these half-lives increased to 3.5 and 7.7 hr. respectively. More than 90% of the radioactivity in plasma of both species was associated with unchanged drug. Species differences exist in the biotransformation of I. Rat urine contained 93-97% I; 2-6% (alpha-cyclopropyl-alpha-hydroxy-p-tolyl)acetic acid (II); and approximately 1% as conjugates. Monkey urine contained I-glucuronide (88%) and unconjugated II (7-10%). In the dog, I-taurine accounted for 27% of the radioactivity found in urine; II and its taurine conjugate accounted for 20 and 30%, respectively; a small quantity of II-glycine (3%) was also detected. There are three minor metabolites that have not been identified. Metabolite II isolated from dog urine was shown to be dextrorotatory."}
{"id": "PMID:238818", "title": "Human metabolism of cyproheptadine.", "content": "Gas-liquid chromatographic and mass, nuclear magnetic resonance, and infrared spectrometric techniques were utilized to identify some of the metabolites of cyproheptadine in the urine of human subjects who had ingested radiolabeled drug. Aromatic ring hydroxylation (followed by glucuronide conjugation), N-demethylation, and heterocyclic ring oxidation were shown to occur in man. The principal metabolite, however, was identified tentatively as a quaternary ammonium, glucuronide-like conjugate of cyproheptadine. No evidence was found for metabolic changes at the tricyclic ethylene bridge in this species.", "contents": "Human metabolism of cyproheptadine. Gas-liquid chromatographic and mass, nuclear magnetic resonance, and infrared spectrometric techniques were utilized to identify some of the metabolites of cyproheptadine in the urine of human subjects who had ingested radiolabeled drug. Aromatic ring hydroxylation (followed by glucuronide conjugation), N-demethylation, and heterocyclic ring oxidation were shown to occur in man. The principal metabolite, however, was identified tentatively as a quaternary ammonium, glucuronide-like conjugate of cyproheptadine. No evidence was found for metabolic changes at the tricyclic ethylene bridge in this species."}
{"id": "PMID:238819", "title": "Studies of the disposition and metabolism of mefloquine HCl (WR 142,490), a quinolinemethanol antimalarial, in the rat. Limited studies with an analog, WR 30,090.", "content": "The overall fate of the quinolinemethanol antimalarial, mefloquine-HCl [WR 142,490, erythro-DL-alpha-(2-piperidyl)-2,9-bis(trifluoromethyl)-4-quinolinemethanol hydrochloride] was investigated in the rat with 14C-labeled drug. Despite its extensive binding to plasma proteins, high tissue/plasma concentration ratios were found. Fecal excretion accounted for most of the drug and metabolites. This fate was rationalized on the basis of physical properties of mefloquine (and its metabolites) and extensive biliary and gastric secretion, followed by reabsorption. Evidence was obtained for the formation of several metabolites. Limited studies were carried out in rats, dogs, and one human subject with another quinolinemethanol, WR 30,090-14C [DL-6,8-dichloro-2-(3',4'-dichlorophenyl)-alpha-(di-n-butylaminomethyl)-4-quinolinemethanol hydrochloride]. Its general fate and physical properties were similar to mefloquine. The disposition of the two quinoline compounds studied was compared to that of quinine and quinidine reported in the literature. This revealed that modification of the quinine molecule resulted in new drugs which were more highly bound and exhibited longer half-lives than quinine.", "contents": "Studies of the disposition and metabolism of mefloquine HCl (WR 142,490), a quinolinemethanol antimalarial, in the rat. Limited studies with an analog, WR 30,090. The overall fate of the quinolinemethanol antimalarial, mefloquine-HCl [WR 142,490, erythro-DL-alpha-(2-piperidyl)-2,9-bis(trifluoromethyl)-4-quinolinemethanol hydrochloride] was investigated in the rat with 14C-labeled drug. Despite its extensive binding to plasma proteins, high tissue/plasma concentration ratios were found. Fecal excretion accounted for most of the drug and metabolites. This fate was rationalized on the basis of physical properties of mefloquine (and its metabolites) and extensive biliary and gastric secretion, followed by reabsorption. Evidence was obtained for the formation of several metabolites. Limited studies were carried out in rats, dogs, and one human subject with another quinolinemethanol, WR 30,090-14C [DL-6,8-dichloro-2-(3',4'-dichlorophenyl)-alpha-(di-n-butylaminomethyl)-4-quinolinemethanol hydrochloride]. Its general fate and physical properties were similar to mefloquine. The disposition of the two quinoline compounds studied was compared to that of quinine and quinidine reported in the literature. This revealed that modification of the quinine molecule resulted in new drugs which were more highly bound and exhibited longer half-lives than quinine."}
{"id": "PMID:238823", "title": "[Treatment of healthy salmonella carriers with lactulose beta-galactosido-fructose (author's transl)].", "content": "Oral administration of lactulose (beta-galactosido-fructose) of 25 healthy Salmonella carriers cured 21, but failed in four.", "contents": "[Treatment of healthy salmonella carriers with lactulose beta-galactosido-fructose (author's transl)]. Oral administration of lactulose (beta-galactosido-fructose) of 25 healthy Salmonella carriers cured 21, but failed in four."}
{"id": "PMID:238820", "title": "The distribution and excretion of 2,4,5,2',5'-pentachlorobiphenyl in the rat.", "content": "Rats received single intravenous doses (0.6 or 6.0 mg/kg) of 2,4,5,2',5'-pentachlorobiphenyl-14C (5-CB). The distribution and ecretion of 5-CB-derived material were investigated at periods ranging from 10 min to 42 days after administration and found to be first-order rate processes in the dose range studied. Blood, liver, muscle, skin, and adipose tissues were found to be the most important tissues to the distribution of this compound. More than 90% of the total dose was removed from the blood within 10 min after administration. Most of the radioactivity was initially deposited in the liver and muscle, and then translocated to the skin and adipose tissue. The decay rate of radioactivity from each of the tissues could be described by the sum of two or more exponentials. Metabolism to more polar compounds appears to be a prerequisite to excretion, and most of the radioactivity was excreted in the bile and ultimately in the feces. Excretion in the urine accounted for less than 7% of the total dose and ceased at approximately 8 or 9 days after 5-CB-administration. Studies of the distribution and excretion of 5-CB-derived material over extended periods of time, 1-42 days, demonstrated the importance of the adipose tissue and skin as long-term storage sites, and demonstrated that the decay rate of 5-CB from the tissues paralleled the decreasing rate of excretion in the feces.", "contents": "The distribution and excretion of 2,4,5,2',5'-pentachlorobiphenyl in the rat. Rats received single intravenous doses (0.6 or 6.0 mg/kg) of 2,4,5,2',5'-pentachlorobiphenyl-14C (5-CB). The distribution and ecretion of 5-CB-derived material were investigated at periods ranging from 10 min to 42 days after administration and found to be first-order rate processes in the dose range studied. Blood, liver, muscle, skin, and adipose tissues were found to be the most important tissues to the distribution of this compound. More than 90% of the total dose was removed from the blood within 10 min after administration. Most of the radioactivity was initially deposited in the liver and muscle, and then translocated to the skin and adipose tissue. The decay rate of radioactivity from each of the tissues could be described by the sum of two or more exponentials. Metabolism to more polar compounds appears to be a prerequisite to excretion, and most of the radioactivity was excreted in the bile and ultimately in the feces. Excretion in the urine accounted for less than 7% of the total dose and ceased at approximately 8 or 9 days after 5-CB-administration. Studies of the distribution and excretion of 5-CB-derived material over extended periods of time, 1-42 days, demonstrated the importance of the adipose tissue and skin as long-term storage sites, and demonstrated that the decay rate of 5-CB from the tissues paralleled the decreasing rate of excretion in the feces."}
{"id": "PMID:238821", "title": "Effect of nafenopin (SU-13,437) on liver functions. Hepatic uptake and biliary excretion of ouabain in the rat.", "content": "Pretreatment of rats for 2 days with the hypolipidemic drug, nafenopin, 0.5 g/kg, results in an increase in liver weight and bile flow. Despite these changes, hepatic transport of ouabain is reduced. This was demonstrated in the isolated perfused liver as well as in vivo. Although net uptake into liver is diminished in treated rats, the initial rapid phase of the plasma disappearance curve is unaffected. This suggests that the primary uptake process is unaffected by nafenopin or is altered in a manner that is not reflected in this phase of plasma disappearance. Alternatively, nafenopin may increase ouabain efflux from liver to plasma. Biliary excretion of ouabain is markedly suppressed after nafenopin pretreatment and higher liver levels of ouabain were encountered after the first 20 min in treated animals. The inference is drawn that liver to bile transport of ouabain is also suppressed by nafenopin pretreatment.", "contents": "Effect of nafenopin (SU-13,437) on liver functions. Hepatic uptake and biliary excretion of ouabain in the rat. Pretreatment of rats for 2 days with the hypolipidemic drug, nafenopin, 0.5 g/kg, results in an increase in liver weight and bile flow. Despite these changes, hepatic transport of ouabain is reduced. This was demonstrated in the isolated perfused liver as well as in vivo. Although net uptake into liver is diminished in treated rats, the initial rapid phase of the plasma disappearance curve is unaffected. This suggests that the primary uptake process is unaffected by nafenopin or is altered in a manner that is not reflected in this phase of plasma disappearance. Alternatively, nafenopin may increase ouabain efflux from liver to plasma. Biliary excretion of ouabain is markedly suppressed after nafenopin pretreatment and higher liver levels of ouabain were encountered after the first 20 min in treated animals. The inference is drawn that liver to bile transport of ouabain is also suppressed by nafenopin pretreatment."}
{"id": "PMID:238828", "title": "Effect of chronic cadmium treatment on rat adrenal catecholamines.", "content": "Daily intraperitoneal injection of cadmium chloride (1 mg/kg) for 45 days significantly increased adrenal weights and augmented the levels of adrenal norepinephrine and epinephrine as well as the activity of adrenal tyrosine hydroxylase. Discontinuation of the heavy metal treatment for 28 days, in rats previously injected with cadmium for 45 days, restored the activity of tyrosine hydroxylase as well as the amount of norepinephrine and epinephrine. In contrast, adrenal weights were restored only partially following the withdrawal of cadmium treatment. Evidence indicates that the changes in adrenal catecholamine metabolism may be the result of stress induced by chronic exposure to this heavy metal. In addition, some of the untoward effects such as hyperglycemia and arterial hypertension seen during cadmium toxicity might be related to increased synthesis of epinephrine in adrenal glands.", "contents": "Effect of chronic cadmium treatment on rat adrenal catecholamines. Daily intraperitoneal injection of cadmium chloride (1 mg/kg) for 45 days significantly increased adrenal weights and augmented the levels of adrenal norepinephrine and epinephrine as well as the activity of adrenal tyrosine hydroxylase. Discontinuation of the heavy metal treatment for 28 days, in rats previously injected with cadmium for 45 days, restored the activity of tyrosine hydroxylase as well as the amount of norepinephrine and epinephrine. In contrast, adrenal weights were restored only partially following the withdrawal of cadmium treatment. Evidence indicates that the changes in adrenal catecholamine metabolism may be the result of stress induced by chronic exposure to this heavy metal. In addition, some of the untoward effects such as hyperglycemia and arterial hypertension seen during cadmium toxicity might be related to increased synthesis of epinephrine in adrenal glands."}
{"id": "PMID:238826", "title": "Sleep and hypnotic drugs.", "content": "In recent years the effectiveness of hypnotic drugs has had to be assessed in terms of a greatly increased knowledge of the physiology and pathology of sleep. The normal pattern of sleep and wakefulness involves a cyclic alternation between three rather than two basically dissimilar states of the brain and body - alert wakefulness, rapid-eye-movement (REM) sleep and non-rapid-eye-movement (NREM) sleep. The pattern of this alternation in individual people results from the interaction of many influences - biological (including genetic, early developmental and later degenerative influences), psychological, social and environmental factors, various physical and psychiatric disorders, and most drugs which affect the central nervous system. The quality of sleep is not related in any simple or constant manner either to its duration or to the proprotions of time spent in each stage of sleep. Among the disorders of sleep, insomnia is a far more common problem of medical management than are enuresis, narcolepsy, somnambulism or nightmares. With a few exceptions, most hypnotic drugs now in widespread use cease to be effective in treating insomnia after the first few nights. However, the ineffective treatment is often continued because insomnia will be even worse during the initial period of drug withdrawal. These factors and the toxicity of hypnotic drugs when taken in overdose make the long-term treatment of insomnia more difficult than was previously supposed. Barbiturates should no longer be prescribed. Some of the non-barbiturates, such as glutethimide and methaqualone, have no advantage over the barbiturates. The benzodiazepine hypnotics, nitrazepam and flurazepam, are less toxic in overdose and are relatively effective in treating insomnia. Chloral hydrate and its derivates are useful alternative drugs for short-term use. Measures to improve sleep without drugs deserve greater emphasis than they have had in the past.", "contents": "Sleep and hypnotic drugs. In recent years the effectiveness of hypnotic drugs has had to be assessed in terms of a greatly increased knowledge of the physiology and pathology of sleep. The normal pattern of sleep and wakefulness involves a cyclic alternation between three rather than two basically dissimilar states of the brain and body - alert wakefulness, rapid-eye-movement (REM) sleep and non-rapid-eye-movement (NREM) sleep. The pattern of this alternation in individual people results from the interaction of many influences - biological (including genetic, early developmental and later degenerative influences), psychological, social and environmental factors, various physical and psychiatric disorders, and most drugs which affect the central nervous system. The quality of sleep is not related in any simple or constant manner either to its duration or to the proprotions of time spent in each stage of sleep. Among the disorders of sleep, insomnia is a far more common problem of medical management than are enuresis, narcolepsy, somnambulism or nightmares. With a few exceptions, most hypnotic drugs now in widespread use cease to be effective in treating insomnia after the first few nights. However, the ineffective treatment is often continued because insomnia will be even worse during the initial period of drug withdrawal. These factors and the toxicity of hypnotic drugs when taken in overdose make the long-term treatment of insomnia more difficult than was previously supposed. Barbiturates should no longer be prescribed. Some of the non-barbiturates, such as glutethimide and methaqualone, have no advantage over the barbiturates. The benzodiazepine hypnotics, nitrazepam and flurazepam, are less toxic in overdose and are relatively effective in treating insomnia. Chloral hydrate and its derivates are useful alternative drugs for short-term use. Measures to improve sleep without drugs deserve greater emphasis than they have had in the past."}
{"id": "PMID:238829", "title": "The effects of adrenalectomy and hydrocortisone replacement on the thyriod of the adult male rat I. Morphometrical data and histochemistry of some oxidative enzymes.", "content": "Morphometrical and histochemical studies were performed to determine the effects of adrenalectomy and hydrocortisone replacement on the rat thyroid. It follows from the performed studies that morphometrical and histochemical changes in the rat thyroid induced by adrenalectomy or hydrocortisone replacement depend upon the duration of the experiment. From the 4th day of the experiment adrenalectomy results in an increase in the volume fraction of the epithelium of the thyroid vesicles with a concomitant decrease of the colloid fraction. As compared to sham operated animals on the 10th day of the experiment the increase in the height of the epithelial cells was seen. Hydrocortisone replacement partially prevents the thyroid changes induced by adrenalectomy, however, this hormone markedly increases the volume fraction of the thyroid stroma and the height of the epithelial cells. On the other hand, histochemical reactions for various oxido-reductases do not provide helpful information for evaluation of the secretory activity of the rat thyroid. It follows from our results that adrenalectomy enhances thyroid stimulation by TSH and enhances the secretory activity of this gland, effects partially prevented by hydrocortisone replacement.", "contents": "The effects of adrenalectomy and hydrocortisone replacement on the thyriod of the adult male rat I. Morphometrical data and histochemistry of some oxidative enzymes. Morphometrical and histochemical studies were performed to determine the effects of adrenalectomy and hydrocortisone replacement on the rat thyroid. It follows from the performed studies that morphometrical and histochemical changes in the rat thyroid induced by adrenalectomy or hydrocortisone replacement depend upon the duration of the experiment. From the 4th day of the experiment adrenalectomy results in an increase in the volume fraction of the epithelium of the thyroid vesicles with a concomitant decrease of the colloid fraction. As compared to sham operated animals on the 10th day of the experiment the increase in the height of the epithelial cells was seen. Hydrocortisone replacement partially prevents the thyroid changes induced by adrenalectomy, however, this hormone markedly increases the volume fraction of the thyroid stroma and the height of the epithelial cells. On the other hand, histochemical reactions for various oxido-reductases do not provide helpful information for evaluation of the secretory activity of the rat thyroid. It follows from our results that adrenalectomy enhances thyroid stimulation by TSH and enhances the secretory activity of this gland, effects partially prevented by hydrocortisone replacement."}
{"id": "PMID:238830", "title": "Effects of de-icing salt on ground water characteristics.", "content": "The effect of \"road salt\" on the characteristics of Massachusetts drinking water supplies has been significant and cumulative rather than transient or seasonal. De-icing salt is essentially all sodium chloride. Calcium chloride accounted for only three percent of the total salt used. However, hardness content, as well as sodium ion concentration, has increased greatly in ground waters in the past decade. The changing composition of our water supplies has agricultural, economic, and public health implications. This study attempts to quantify the stoichiometry of these changes in concentration, which are in part due to an ion-exchange mechanism in the soil.", "contents": "Effects of de-icing salt on ground water characteristics. The effect of \"road salt\" on the characteristics of Massachusetts drinking water supplies has been significant and cumulative rather than transient or seasonal. De-icing salt is essentially all sodium chloride. Calcium chloride accounted for only three percent of the total salt used. However, hardness content, as well as sodium ion concentration, has increased greatly in ground waters in the past decade. The changing composition of our water supplies has agricultural, economic, and public health implications. This study attempts to quantify the stoichiometry of these changes in concentration, which are in part due to an ion-exchange mechanism in the soil."}
{"id": "PMID:238832", "title": "The effect of vitamin E on NO2 induced redox changes in the human erythrocyte.", "content": "Human erythrocytes admixed with vitamin E supplements (50 mug/ml) were exposed to NO2 in concentrations of 200-600 p.p.m. at 37 degrees C for 2 h.  No protective effect against the increase in the redox ratio [NAD+]/[NADH]normally produced by NO2 was observed.  It is postulated that NO2 increases the redox ratio by a mechanism independent of that producing hemolysis and prevented by vitamin E.  This may involve alteration of NADH dependent enzymes by NO2.", "contents": "The effect of vitamin E on NO2 induced redox changes in the human erythrocyte. Human erythrocytes admixed with vitamin E supplements (50 mug/ml) were exposed to NO2 in concentrations of 200-600 p.p.m. at 37 degrees C for 2 h.  No protective effect against the increase in the redox ratio [NAD+]/[NADH]normally produced by NO2 was observed.  It is postulated that NO2 increases the redox ratio by a mechanism independent of that producing hemolysis and prevented by vitamin E.  This may involve alteration of NADH dependent enzymes by NO2."}
{"id": "PMID:238833", "title": "Influences of exercise and endurance training on the oxygen dissociation curve of blood under in vivo and in vitro conditions.", "content": "In experiments with graded exercise of 15 men (6 untrained, 3 semitrained, 6 endurance-trained) the trained subjects showed a massive shift to the right of the in vivo O2 dissociation curve (ODC) of femoral venous blood. At a saturation of 20 to 25% (18 mkp/sec) Po2 was about 9 mm Hg higher for the trained than for the untrained group. The following factors play a role: 1. The 2,3-diphosphoglycerate [2,3-DPG] concentration was increased by 15 to 20% in the trained group which explains about 2 mm Hg of the diffenence in Po2-2. Exercise acidosis in the femoral venous blood depends to a large extent on CO2 in the trained, but on lactic acid in the untrained group. At low saturations the CO2-Bohr effect increases sharply thus having a greater importance in the trained subjects. This factor can explain about 2 mm Hg of the difference. However, influence of chloride and 2,3-DPG on the Bohr effect must be taken into consideration. 3. Since the large ODC-shift to the right of the trained group was not reproducible under in vitro conditions, it is suggested that a rapidly decaying unknown substance accounts for the remaining difference in Po2.", "contents": "Influences of exercise and endurance training on the oxygen dissociation curve of blood under in vivo and in vitro conditions. In experiments with graded exercise of 15 men (6 untrained, 3 semitrained, 6 endurance-trained) the trained subjects showed a massive shift to the right of the in vivo O2 dissociation curve (ODC) of femoral venous blood. At a saturation of 20 to 25% (18 mkp/sec) Po2 was about 9 mm Hg higher for the trained than for the untrained group. The following factors play a role: 1. The 2,3-diphosphoglycerate [2,3-DPG] concentration was increased by 15 to 20% in the trained group which explains about 2 mm Hg of the diffenence in Po2-2. Exercise acidosis in the femoral venous blood depends to a large extent on CO2 in the trained, but on lactic acid in the untrained group. At low saturations the CO2-Bohr effect increases sharply thus having a greater importance in the trained subjects. This factor can explain about 2 mm Hg of the difference. However, influence of chloride and 2,3-DPG on the Bohr effect must be taken into consideration. 3. Since the large ODC-shift to the right of the trained group was not reproducible under in vitro conditions, it is suggested that a rapidly decaying unknown substance accounts for the remaining difference in Po2."}
{"id": "PMID:238834", "title": "Diurnal changes of the 2,3-diphosphoglycerate concentration in human red cells and the influence of posture.", "content": "The 2,3-diphosphoglycerate (2,3-DPG) concentration, oxygen half saturation pressure at pH 7.4 (P50), pH in plasma and red cells, and mean corpuscular hemoglobin concentration (MCHC) of venous blood were determined during unrestricted daily activity (series I) throughout 24 hrs as well as during prolonged bed rest until noon (series II). In series I almost synchronous dirunal behavior of P50 2,3-DPG, and plasma pH as well as red cell pH became significantly apparent with highest values in the afternoon. The [2,3-DPG] yielded most pronounced alterations, which made up to 13.5% of the average day value. During prolonged recumbency the [2,3-DPG] showed a nonsignificant tendency to decline; the P50 remained unchanged throughout that period. The possible reason for the missing [2,3-DPG] increase is a reduced change of red cell pH in series II. An influence of a posture dependent aldosterone secretion either directly on the 2,3-DPG metabloism of indirectly via mediating the red cell pH and thus ruling the formation of this organic PHOSPHORIS COMPOUND IS DISCUSSED.", "contents": "Diurnal changes of the 2,3-diphosphoglycerate concentration in human red cells and the influence of posture. The 2,3-diphosphoglycerate (2,3-DPG) concentration, oxygen half saturation pressure at pH 7.4 (P50), pH in plasma and red cells, and mean corpuscular hemoglobin concentration (MCHC) of venous blood were determined during unrestricted daily activity (series I) throughout 24 hrs as well as during prolonged bed rest until noon (series II). In series I almost synchronous dirunal behavior of P50 2,3-DPG, and plasma pH as well as red cell pH became significantly apparent with highest values in the afternoon. The [2,3-DPG] yielded most pronounced alterations, which made up to 13.5% of the average day value. During prolonged recumbency the [2,3-DPG] showed a nonsignificant tendency to decline; the P50 remained unchanged throughout that period. The possible reason for the missing [2,3-DPG] increase is a reduced change of red cell pH in series II. An influence of a posture dependent aldosterone secretion either directly on the 2,3-DPG metabloism of indirectly via mediating the red cell pH and thus ruling the formation of this organic PHOSPHORIS COMPOUND IS DISCUSSED."}
{"id": "PMID:238835", "title": "Studies on energy-linked reactions: isolation and properties of mitochondrial venturicidin-resistant mutants of Saccharomyces cerevisiae.", "content": "Venturicidin is a specific inhibitor of aerobic growth of yeast and has no effect on fermentative growth, a result which is consistent with its known mode of action on mitochondrial oxidative phosphorylation. Venturicidin-resistant mutants of Saccharomyces cerevisiae have been isolated and form two general classes: class 1, nuclear mutants which are resistant to a variety of mitochondrial inhibitors and uncouplers, and class 2, mitochondrial mutants of phenotype VENR OLYR and VENR TETR in vivo. VENR OLYR mutants show a high degree of resistance to venturicidin and oligomycin at the whole cell and mitochondrial ATPase level but, in contrast, no resistance at the mitochondrial level is observed with VENR TETR mutants. Venturicidin resistance/sensitivity can be correlated with two binding sites on mitochondrial ATPase, one of which is common to the oligomycin binding site and the other is common to the triethyl tin binding site. Biochemical genetic studies indicate that two mitochondrial genes specify venturicidin resistance/sensitivity and that the mitochondrial gene products are components of the mitochondrial ATPase complex.", "contents": "Studies on energy-linked reactions: isolation and properties of mitochondrial venturicidin-resistant mutants of Saccharomyces cerevisiae. Venturicidin is a specific inhibitor of aerobic growth of yeast and has no effect on fermentative growth, a result which is consistent with its known mode of action on mitochondrial oxidative phosphorylation. Venturicidin-resistant mutants of Saccharomyces cerevisiae have been isolated and form two general classes: class 1, nuclear mutants which are resistant to a variety of mitochondrial inhibitors and uncouplers, and class 2, mitochondrial mutants of phenotype VENR OLYR and VENR TETR in vivo. VENR OLYR mutants show a high degree of resistance to venturicidin and oligomycin at the whole cell and mitochondrial ATPase level but, in contrast, no resistance at the mitochondrial level is observed with VENR TETR mutants. Venturicidin resistance/sensitivity can be correlated with two binding sites on mitochondrial ATPase, one of which is common to the oligomycin binding site and the other is common to the triethyl tin binding site. Biochemical genetic studies indicate that two mitochondrial genes specify venturicidin resistance/sensitivity and that the mitochondrial gene products are components of the mitochondrial ATPase complex."}
{"id": "PMID:238836", "title": "Catalytically active azoaldolase. Preparation on solid support.", "content": "A procedure for the coupling at pH 7.2 of p-carboxy benzene diazonium chloride with rabbit muscle aldolase supported on phosphocellulose is described and some of the spectroscopic, structural and catalytic features of the material obtained are reported. The tetrameric azoenzyme is homogeneous in disc gel electrophoresis even in the presence of 8 M urea. Twelve molecules of the reactant are bound to the protein. Eight azocysteins are identified by both spectroscopic studies and amino acid analysis. The presence of one azohistidine is suggested by the spectroscopic data along with the presence of other, as yet unknown, chromophores. The azoaldolase shows unchanged catalytic properties using both D-fructose 1,6-bisphosphate and D-fructose 1-phosphate as substrates, as compared with the native enzyme. The pH profile of the enzyme activity is broadened towards the alkaline region but no changes occur in the physiological range of pH.", "contents": "Catalytically active azoaldolase. Preparation on solid support. A procedure for the coupling at pH 7.2 of p-carboxy benzene diazonium chloride with rabbit muscle aldolase supported on phosphocellulose is described and some of the spectroscopic, structural and catalytic features of the material obtained are reported. The tetrameric azoenzyme is homogeneous in disc gel electrophoresis even in the presence of 8 M urea. Twelve molecules of the reactant are bound to the protein. Eight azocysteins are identified by both spectroscopic studies and amino acid analysis. The presence of one azohistidine is suggested by the spectroscopic data along with the presence of other, as yet unknown, chromophores. The azoaldolase shows unchanged catalytic properties using both D-fructose 1,6-bisphosphate and D-fructose 1-phosphate as substrates, as compared with the native enzyme. The pH profile of the enzyme activity is broadened towards the alkaline region but no changes occur in the physiological range of pH."}
{"id": "PMID:238837", "title": "The reversible depolymerization of spinach chloroplast glyceraldehyde-phosphate dehydrogenase. Interaction with nucleotides and dithiothreitol.", "content": "The ligand-dependent dissociation of spinach chloroplast glyceraldehyde-phosphate dehydrogenase (Mr 600000) to protomers of Mr about 145000, previously shown by us in 1973, has been further characterized by the technique of velocity sedimentation in sucrose gradients. The process exhibits cooperativity and is accompanied by an increase of the apparent NADP+-dependent activity (reactivation) from a ratio of 0.1-0.2 to a ratio of 1 to 2 with respect to the NAD+-dependent activity. In addition to NADP+ and NADPH, most nucleotide triphosphates and, to some extent, Pi, act as dissociating agents. The enzyme is depolymerized and progressively inactivated in the presence of 2'-AMP. 2. Incubation with 20 mM dithiothreitol or 8-10 mM GTP increases the apparent NADP/H)-dependent activity, although addition of a small amount of a dissociating compound, such as 0.06 mM NADP+, is required for depolymerization. 3. NAD+, NADH and, to a lesser extent, glyceraldehyde 3-phosphate, NMN and cyclic AMP act as inhibitors of the dissociation and reactivation, however induced. They also favour the reassociation of protomers to tetramers. 4. The NADP(H)-linked activity is probably a property of the protomers only. The system described here resembles in many respects the light-dependent regulation of the NADP(H)-linked activity in vivo.", "contents": "The reversible depolymerization of spinach chloroplast glyceraldehyde-phosphate dehydrogenase. Interaction with nucleotides and dithiothreitol. The ligand-dependent dissociation of spinach chloroplast glyceraldehyde-phosphate dehydrogenase (Mr 600000) to protomers of Mr about 145000, previously shown by us in 1973, has been further characterized by the technique of velocity sedimentation in sucrose gradients. The process exhibits cooperativity and is accompanied by an increase of the apparent NADP+-dependent activity (reactivation) from a ratio of 0.1-0.2 to a ratio of 1 to 2 with respect to the NAD+-dependent activity. In addition to NADP+ and NADPH, most nucleotide triphosphates and, to some extent, Pi, act as dissociating agents. The enzyme is depolymerized and progressively inactivated in the presence of 2'-AMP. 2. Incubation with 20 mM dithiothreitol or 8-10 mM GTP increases the apparent NADP/H)-dependent activity, although addition of a small amount of a dissociating compound, such as 0.06 mM NADP+, is required for depolymerization. 3. NAD+, NADH and, to a lesser extent, glyceraldehyde 3-phosphate, NMN and cyclic AMP act as inhibitors of the dissociation and reactivation, however induced. They also favour the reassociation of protomers to tetramers. 4. The NADP(H)-linked activity is probably a property of the protomers only. The system described here resembles in many respects the light-dependent regulation of the NADP(H)-linked activity in vivo."}
{"id": "PMID:238838", "title": "Heme reactivity of hemoglobins. Azide and fluoride binding equilibria of free and mercuriated ferri-gamma chains.", "content": "The free gamma chains, isolated from human foetal hemoglobin, are stable when oxidized and thus suitable for ligand binding and subunit equilibrium studies. The metaquo-ferri chains, with cysteine-F9 in the free state II ag gamma SH) possess several properties which are different from those of their p-mercuribenzoate derivative (III aq gammaSHgR); these are: stronger binding of a high-field ligand (N3- minus), altered spin equilibrium and an altered subunit equilibrium. A quantitative assessment of the free energy changes associated with all individual steps involved in changing the metaquo chains to their azide derivatives has been made. The results show that the higher apparent reactivity of III ag gammaSH (compared to IIIaq gammaSHgR) for the azide ion is not solely due to compensatory effects arising from differences of subunit dissociation or of spin equilibrium: other process(es) occurring in the ligand binding site have to be considered.", "contents": "Heme reactivity of hemoglobins. Azide and fluoride binding equilibria of free and mercuriated ferri-gamma chains. The free gamma chains, isolated from human foetal hemoglobin, are stable when oxidized and thus suitable for ligand binding and subunit equilibrium studies. The metaquo-ferri chains, with cysteine-F9 in the free state II ag gamma SH) possess several properties which are different from those of their p-mercuribenzoate derivative (III aq gammaSHgR); these are: stronger binding of a high-field ligand (N3- minus), altered spin equilibrium and an altered subunit equilibrium. A quantitative assessment of the free energy changes associated with all individual steps involved in changing the metaquo chains to their azide derivatives has been made. The results show that the higher apparent reactivity of III ag gammaSH (compared to IIIaq gammaSHgR) for the azide ion is not solely due to compensatory effects arising from differences of subunit dissociation or of spin equilibrium: other process(es) occurring in the ligand binding site have to be considered."}
{"id": "PMID:238839", "title": "The mitochondrial ATPase. Evidence for a single essential tyrosine residue.", "content": "1. Evidence is presented which indicates that inactivation of the mitochondrial ATPase from bovine heart by the reagent 4-chloro-7-nitrobenzofurazan results from modification of one tyrosine residue per enzyme molecule. Activity can be restored by a variety of sulphydryl reagents. 2. In sodium dodecyl sulphate, the nitrogenzofurazan group on tyrosine is transfered to newly exposed sulphydryl groups on the enzyme. 3. The rate of transfer of the nitrobenzofurazan moiety from theenzyme to sulphydryl compounds is compared with that for transfer from the model compound N-acetyl-tyrosine-0(7-nitrobenzo-furazan) ethyl ester, the synthesis and properties of which are also described. 4. The ligands ATP and ADP exert a protective effect on the rate of reaction between the mitochondrial ATPase and 4-chloro-7-nitrobenzofurazan. The variation in rate of this reaction with change in pH has also been examined and a pKa of 9.5 estimated for the tyrosine residue. 5. The modification does not prevent substrate binding as judged by changes in the fluorescence of aurovertin, an antibiotic with specific affinity for mitochondiral ATPases. 6. When the ATPase activity of submitochondrial particles is inhibited by 4-chloro-7-nitrobenzo-furazan, there is a parallel decrease in the extent of the energy-linked fluorescence enhancement of 1-anilino-naphthalene-8-sulphonate induced by ATP hydrolysis. Both ATPase activity and the fluorescence enhancement are restored by sluphydryl reagents.", "contents": "The mitochondrial ATPase. Evidence for a single essential tyrosine residue. 1. Evidence is presented which indicates that inactivation of the mitochondrial ATPase from bovine heart by the reagent 4-chloro-7-nitrobenzofurazan results from modification of one tyrosine residue per enzyme molecule. Activity can be restored by a variety of sulphydryl reagents. 2. In sodium dodecyl sulphate, the nitrogenzofurazan group on tyrosine is transfered to newly exposed sulphydryl groups on the enzyme. 3. The rate of transfer of the nitrobenzofurazan moiety from theenzyme to sulphydryl compounds is compared with that for transfer from the model compound N-acetyl-tyrosine-0(7-nitrobenzo-furazan) ethyl ester, the synthesis and properties of which are also described. 4. The ligands ATP and ADP exert a protective effect on the rate of reaction between the mitochondrial ATPase and 4-chloro-7-nitrobenzofurazan. The variation in rate of this reaction with change in pH has also been examined and a pKa of 9.5 estimated for the tyrosine residue. 5. The modification does not prevent substrate binding as judged by changes in the fluorescence of aurovertin, an antibiotic with specific affinity for mitochondiral ATPases. 6. When the ATPase activity of submitochondrial particles is inhibited by 4-chloro-7-nitrobenzo-furazan, there is a parallel decrease in the extent of the energy-linked fluorescence enhancement of 1-anilino-naphthalene-8-sulphonate induced by ATP hydrolysis. Both ATPase activity and the fluorescence enhancement are restored by sluphydryl reagents."}
{"id": "PMID:238840", "title": "The mitochondrial ATPase. Selective modification of a nitrogen residue in the beta subunit.", "content": "1. When mitochondrial ATPase, which has been modified on a single tyrosine residue by 4-chloro-7-nitrobenzofurazan, is incubated at pH 9.0, the 7-nitrobenzofurazan group undergoes an intramolecular transfer to a nitrogen residue. The rate of this transfer is sensitive to the binding of adenine nucleotides to the enzyme. The resulting N-nitrobenzofurazan ATPase has little or no activity. 2. The fluorescence of the N-nitrobenzofurazan group in the modified ATPase is quenched on binding of ADP. 3. Electrophoresis of the modified enzyme in sodium dodecyl sulphate on a 10% polyacrylamide gel shows that the fluorescence of the N-nitrobenzofurazan chromophore is exclusively in the beta subunit. 4. The rate of transfer of the nitrobenzofurazan group from tyrosyl oxygen to nitrogen on the enzyme is compared with the rate of transfer between model compounds. 5. The interaction of the N-nitrobenzofurazan ATPase with aurovertin is reported.", "contents": "The mitochondrial ATPase. Selective modification of a nitrogen residue in the beta subunit. 1. When mitochondrial ATPase, which has been modified on a single tyrosine residue by 4-chloro-7-nitrobenzofurazan, is incubated at pH 9.0, the 7-nitrobenzofurazan group undergoes an intramolecular transfer to a nitrogen residue. The rate of this transfer is sensitive to the binding of adenine nucleotides to the enzyme. The resulting N-nitrobenzofurazan ATPase has little or no activity. 2. The fluorescence of the N-nitrobenzofurazan group in the modified ATPase is quenched on binding of ADP. 3. Electrophoresis of the modified enzyme in sodium dodecyl sulphate on a 10% polyacrylamide gel shows that the fluorescence of the N-nitrobenzofurazan chromophore is exclusively in the beta subunit. 4. The rate of transfer of the nitrobenzofurazan group from tyrosyl oxygen to nitrogen on the enzyme is compared with the rate of transfer between model compounds. 5. The interaction of the N-nitrobenzofurazan ATPase with aurovertin is reported."}
{"id": "PMID:238841", "title": "Photoinactivation and carbethoxylation of leucine aminopeptidase.", "content": "In the present paper the reactivity of histidyl residues of leucine aminopeptidase from bovine eye lens was studied by dye-sensitized photooxidation and by carbethoxylation of the enzyme protein using diethylpyrocarbonate. Of all the different amino acids modified by photooxidation only histidine is connected with the enzymic acticity, whereas tyrosine seems to be involved in structure stabilization. By changing the pH and varying the effectors (Mg2+ and/or dodecylsulfate) of the reaction mixture a different number of histidyl residues of the enzyme protein is caused to react with diethylpyrocarbonate. No secondary reactions with tyrosyl or tryptophyl residues could be observed by spectrophotometric investigations. The enzyme modified by one of the above-mentioned methods shows changes in the capacity of Mn2+ binding measured by autoradiography as well as in the degree of enhancement of enzymic activity by Mn2+ or Mg2+ ions. Of the 48 histidyl residues of the enzyme (Mr = 326000) up to 2 histidyl residues per subunit (Mr = 54000) may be involved in Mn2+ or Mg2+ binding and up to 4 histidyl residues have a strong influence on Zn2+ binding.", "contents": "Photoinactivation and carbethoxylation of leucine aminopeptidase. In the present paper the reactivity of histidyl residues of leucine aminopeptidase from bovine eye lens was studied by dye-sensitized photooxidation and by carbethoxylation of the enzyme protein using diethylpyrocarbonate. Of all the different amino acids modified by photooxidation only histidine is connected with the enzymic acticity, whereas tyrosine seems to be involved in structure stabilization. By changing the pH and varying the effectors (Mg2+ and/or dodecylsulfate) of the reaction mixture a different number of histidyl residues of the enzyme protein is caused to react with diethylpyrocarbonate. No secondary reactions with tyrosyl or tryptophyl residues could be observed by spectrophotometric investigations. The enzyme modified by one of the above-mentioned methods shows changes in the capacity of Mn2+ binding measured by autoradiography as well as in the degree of enhancement of enzymic activity by Mn2+ or Mg2+ ions. Of the 48 histidyl residues of the enzyme (Mr = 326000) up to 2 histidyl residues per subunit (Mr = 54000) may be involved in Mn2+ or Mg2+ binding and up to 4 histidyl residues have a strong influence on Zn2+ binding."}
{"id": "PMID:238842", "title": "The effects of spermine and Mg2+ on the catalytic mechanism of isoleucine: tRNA ligase.", "content": "Isoleucyl-tRNA formation catalysed by isoleucine: tRNA ligase is stimulated by both Mg2+ and spermine in the pH-range 7.0 to 8.0 at 310 K. At low [Mg2+] the acceleration caused by both cations together exceeds the sum of their individual effects. 2. The spermine-stimulated reaction has a steeper temperature-dependence than reaction in the presence of Mg2+. Two phases in the kinetics of isoleucyl-tRNA formation are detected in the presence of Mg2+ plus or minus spermine, but only a single step is observed in the presence of spermine alone. Thus the rate-limiting steps under normal assay conditions are different for the two cations. 3. Enzyme-bound isoleucyl-AMP can be formed in the absence of Mg-2+ and plus or minus spermine. 4. It is concluded that there is no evidence for cation-dependent differences in the reaction mechanism of isoleucine: tRNA ligase, though there are certainly differences in the relative rates of some of the individual steps.", "contents": "The effects of spermine and Mg2+ on the catalytic mechanism of isoleucine: tRNA ligase. Isoleucyl-tRNA formation catalysed by isoleucine: tRNA ligase is stimulated by both Mg2+ and spermine in the pH-range 7.0 to 8.0 at 310 K. At low [Mg2+] the acceleration caused by both cations together exceeds the sum of their individual effects. 2. The spermine-stimulated reaction has a steeper temperature-dependence than reaction in the presence of Mg2+. Two phases in the kinetics of isoleucyl-tRNA formation are detected in the presence of Mg2+ plus or minus spermine, but only a single step is observed in the presence of spermine alone. Thus the rate-limiting steps under normal assay conditions are different for the two cations. 3. Enzyme-bound isoleucyl-AMP can be formed in the absence of Mg-2+ and plus or minus spermine. 4. It is concluded that there is no evidence for cation-dependent differences in the reaction mechanism of isoleucine: tRNA ligase, though there are certainly differences in the relative rates of some of the individual steps."}
{"id": "PMID:238843", "title": "Proton-magnetic-resonance studies of the lysine residues of ribonuclease A.", "content": "The amino groups of ribonuclease A (RNase-A) have been methylated with formaldehyde and borohydride to provide observable resonances for proton magnetic resonance (PMR) studies. Although enzymatic activity is lost, PMR difference spectroscopy and PMR studies of thermal denaturation show native conformation is largely preserved in methylated RNase-A. Resonances corresponding to the NH2-terminal alpha-amino and 10 xi-amino N-methyl groups are titrated at 220 MHz to obtain pK values. After correction for the effects of methylation, using values previously derived from model compound studies, a pK of 6.6 is found for the alpha-amino group, a pK of 8.6 for the xi-amino group of lysine-41 and pK values ranging from 10.6 to 11.2 for the other lysine xi-amino groups. Interactions between lysine-7 and lysine-41 or between the alpha-amino and xi-amino groups of lysine-1 have been proposed to account for deviations from simple titration behaviour. The correct continuities for the titration curves of the histidine H-2 proton resonances have been confirmed by selective deuteration of the H-2 protons. Titration curves for the H-2 proton resonances of histidine-12 and histidine-119 of methylated RNase-A show deviations from the titration curves for the native enzyme, indicating some alteration of the active-site conformation. In the presence of phosphate, titration curves for the H-2 proton resonances of histidine-12 and histidine-119 of methylated RNase-A indicate binding of phosphate at the active site, but these curves continue to show deviations from the titration behaviour of native RNase-A. The titration curve for the N-methyl resonance of lysine-41 is perturbed considerably by the presence of phosphate, which indicates a possible catalytic role for lysine-41.", "contents": "Proton-magnetic-resonance studies of the lysine residues of ribonuclease A. The amino groups of ribonuclease A (RNase-A) have been methylated with formaldehyde and borohydride to provide observable resonances for proton magnetic resonance (PMR) studies. Although enzymatic activity is lost, PMR difference spectroscopy and PMR studies of thermal denaturation show native conformation is largely preserved in methylated RNase-A. Resonances corresponding to the NH2-terminal alpha-amino and 10 xi-amino N-methyl groups are titrated at 220 MHz to obtain pK values. After correction for the effects of methylation, using values previously derived from model compound studies, a pK of 6.6 is found for the alpha-amino group, a pK of 8.6 for the xi-amino group of lysine-41 and pK values ranging from 10.6 to 11.2 for the other lysine xi-amino groups. Interactions between lysine-7 and lysine-41 or between the alpha-amino and xi-amino groups of lysine-1 have been proposed to account for deviations from simple titration behaviour. The correct continuities for the titration curves of the histidine H-2 proton resonances have been confirmed by selective deuteration of the H-2 protons. Titration curves for the H-2 proton resonances of histidine-12 and histidine-119 of methylated RNase-A show deviations from the titration curves for the native enzyme, indicating some alteration of the active-site conformation. In the presence of phosphate, titration curves for the H-2 proton resonances of histidine-12 and histidine-119 of methylated RNase-A indicate binding of phosphate at the active site, but these curves continue to show deviations from the titration behaviour of native RNase-A. The titration curve for the N-methyl resonance of lysine-41 is perturbed considerably by the presence of phosphate, which indicates a possible catalytic role for lysine-41."}
{"id": "PMID:238844", "title": "Studies on the de novo biosynthesis of NAD in Escherichia coli. The separation of the nadB gene product from the nadA gene product and its purification.", "content": "Quinolinic acid (pyridine 2,3-dicarboxylic acid) which is an immediate precursor of the pyridine nucleotides, is synthesised from L-asparate and dihydroxyacetone phosphate in Escherichia coli. Extracts from certain nadB mutants complement the extracts prepared from all nadA mutants for the enzymic synthesis of quinolinate. Using the complementation assay, the quinolinate synthetase B protein has been purified more than 300-fold. The quinolinate synthetase B protein exists in all nadA and nadC mutants examined. The quinolinate synthetase A protein was present in all nadC mutants and most (but not all) nadB mutants. The facile separation of the wild-type quinolinate synthetase A and B proteins out of a nadC mutant suggests that quinolinate synthetase does not exists as a tightly bound complex. The partially purified quinolinate synthetase is inhibited by physiological concetrations of NAD and NADH but not by NADP or NADPH.", "contents": "Studies on the de novo biosynthesis of NAD in Escherichia coli. The separation of the nadB gene product from the nadA gene product and its purification. Quinolinic acid (pyridine 2,3-dicarboxylic acid) which is an immediate precursor of the pyridine nucleotides, is synthesised from L-asparate and dihydroxyacetone phosphate in Escherichia coli. Extracts from certain nadB mutants complement the extracts prepared from all nadA mutants for the enzymic synthesis of quinolinate. Using the complementation assay, the quinolinate synthetase B protein has been purified more than 300-fold. The quinolinate synthetase B protein exists in all nadA and nadC mutants examined. The quinolinate synthetase A protein was present in all nadC mutants and most (but not all) nadB mutants. The facile separation of the wild-type quinolinate synthetase A and B proteins out of a nadC mutant suggests that quinolinate synthetase does not exists as a tightly bound complex. The partially purified quinolinate synthetase is inhibited by physiological concetrations of NAD and NADH but not by NADP or NADPH."}
{"id": "PMID:238845", "title": "Biotin carboxyl carrier protein in barley chloroplast membranes.", "content": "Biotin localized in barley chloroplast lamellae is covalently bound to a single protein with an approximate molecular weight of 21 000. It contains one mole of biotin per mole of protein and functions as a carboxyl carrier in the acetyl-CoA carboxylase reaction. The protein was obtained by solubilization of the lamellae in phenol/acetic acid/8 M urea. Feeding barley seedlings with [14C]-biotin revealed that the vitamin is not degraded into respiratory substrates by the plant, but is specifically incorporated into biotin carboxyl carrier protein.", "contents": "Biotin carboxyl carrier protein in barley chloroplast membranes. Biotin localized in barley chloroplast lamellae is covalently bound to a single protein with an approximate molecular weight of 21 000. It contains one mole of biotin per mole of protein and functions as a carboxyl carrier in the acetyl-CoA carboxylase reaction. The protein was obtained by solubilization of the lamellae in phenol/acetic acid/8 M urea. Feeding barley seedlings with [14C]-biotin revealed that the vitamin is not degraded into respiratory substrates by the plant, but is specifically incorporated into biotin carboxyl carrier protein."}
{"id": "PMID:238846", "title": "Substrate stereochemistry of the acetyl-CoA acetyltransferase reaction.", "content": "1. A specimen of symmetrically tritiated 3S-3-hydroxy[2-3H2]butyryl-CoA was prepared from acetoacetyl-CoA by incubation in tritiated water, followed by enzymic reduction using 3S-specific 3-hydroxyacyl-CoA dehydrogenase. In addition, a specimen of dideuterated, racemic 3RS-3-hydroxy-[2-2H2]butyryl-CoA was prepared chemically from 3RS-3-hydroxy[2-2H2]butyric acid. 2. These acyl-CoA derivatives were incubated respectively with deuterium oxide and tritated water in presence of enoyl-CoA hydratase. Stereospecifically tritiated compounds, respectively 2S,3S-3-hydroxy[2-2H1,3H1]butyryl-CoA and 2R,3S-3-hydroxy[2-1H1,3H1]butyryl-CoA (plus 3R-diastereomer) were formed and isolated. 3. 3S-3-Hydroxy[2-3H2]butyryl-CoA and the 3S-[2-3H2,3-14C]-labelled material were also prepared as described in the preceding paper. The latter substrate was used to establish conditions in which little loss of tritium would occur (found; about 7%) on cleavage to acetyl-CoA in the presence of 3-hydroxyacyl-CoA dehydrogenase and acetyl-CoA acetyltransferase. Little loss of tritium indicates a small degree of racemization of the stereospecifically 2-tritiated 3-hydroxyacyl-CoA derivatives at the level of transiently formed acetoacetyl-CoA and acetyl-CoA. This ensures high optical purity of the chiral acetates generated from the stereospecifically tritiated hydroxybutyryl-CoA specimens listed in paragraph (2). 4. These two acyl-CoA derivatives and the symmetrically tritiated 3S-3-hydroxy[2-3H2]butyryl-CoA listed in paragraph (3) were converted to the acetates enzymically in the sequence hydroxy-butyryl-CoA leads to acetoacetyl-CoA leads to acetyl-CoA leads to acetate. The isolated acetates were assayed for chirality by conversion to the malates and fumarates as usual. 5. The malate formed from 3S-3-hydroxy[2-3H2]butyryl-CoA on incubation with fumarase lost nearly 50%, that derived from 2R,3S-3-hydroxy[2-2H1,3H1]butyryl-CoA (plus 3R-diastereomer) retained about 26% and that derived from 2S,3S-3-hydroxy[2-1H1,3H1]butyryl-CoA retained about 78% of its total tritium content. 6. It was concluded that the detachment of acetyl-CoA from acetoacetyl-CoA on acetyl-CoA acetyltransferase occurs with inversion of configuration at the methylene group which becomes methyl.", "contents": "Substrate stereochemistry of the acetyl-CoA acetyltransferase reaction. 1. A specimen of symmetrically tritiated 3S-3-hydroxy[2-3H2]butyryl-CoA was prepared from acetoacetyl-CoA by incubation in tritiated water, followed by enzymic reduction using 3S-specific 3-hydroxyacyl-CoA dehydrogenase. In addition, a specimen of dideuterated, racemic 3RS-3-hydroxy-[2-2H2]butyryl-CoA was prepared chemically from 3RS-3-hydroxy[2-2H2]butyric acid. 2. These acyl-CoA derivatives were incubated respectively with deuterium oxide and tritated water in presence of enoyl-CoA hydratase. Stereospecifically tritiated compounds, respectively 2S,3S-3-hydroxy[2-2H1,3H1]butyryl-CoA and 2R,3S-3-hydroxy[2-1H1,3H1]butyryl-CoA (plus 3R-diastereomer) were formed and isolated. 3. 3S-3-Hydroxy[2-3H2]butyryl-CoA and the 3S-[2-3H2,3-14C]-labelled material were also prepared as described in the preceding paper. The latter substrate was used to establish conditions in which little loss of tritium would occur (found; about 7%) on cleavage to acetyl-CoA in the presence of 3-hydroxyacyl-CoA dehydrogenase and acetyl-CoA acetyltransferase. Little loss of tritium indicates a small degree of racemization of the stereospecifically 2-tritiated 3-hydroxyacyl-CoA derivatives at the level of transiently formed acetoacetyl-CoA and acetyl-CoA. This ensures high optical purity of the chiral acetates generated from the stereospecifically tritiated hydroxybutyryl-CoA specimens listed in paragraph (2). 4. These two acyl-CoA derivatives and the symmetrically tritiated 3S-3-hydroxy[2-3H2]butyryl-CoA listed in paragraph (3) were converted to the acetates enzymically in the sequence hydroxy-butyryl-CoA leads to acetoacetyl-CoA leads to acetyl-CoA leads to acetate. The isolated acetates were assayed for chirality by conversion to the malates and fumarates as usual. 5. The malate formed from 3S-3-hydroxy[2-3H2]butyryl-CoA on incubation with fumarase lost nearly 50%, that derived from 2R,3S-3-hydroxy[2-2H1,3H1]butyryl-CoA (plus 3R-diastereomer) retained about 26% and that derived from 2S,3S-3-hydroxy[2-1H1,3H1]butyryl-CoA retained about 78% of its total tritium content. 6. It was concluded that the detachment of acetyl-CoA from acetoacetyl-CoA on acetyl-CoA acetyltransferase occurs with inversion of configuration at the methylene group which becomes methyl."}
{"id": "PMID:238847", "title": "The reactive sites of Kunitz bovine-trypsin inhibitor. Role of lysine-15 in the interaction with chymotrypsin.", "content": "Kunitz bovine trypsin inhibitor gave with alpha-chymotrypsin a stoichiometric complex stable at neutral pH. The complex has been characteristized by amino acid composition, molecular sieving and zone electrophoresis. Complete dissociation occurred at pH 4.0 as shown by gel filtration, alpha-Chymotrypsin was displaced from the complex by trypsin either in solution or by affinity chromatography on trypsin-Sepharos: alpha-chymotrypsin was recovered in the filtrate (yield about 100%) and the inhibitor was eluted from trypsin-Sepharose with 0.1 M HCl (yield: 83%). Lysine-15 of the inhibitor was shown to be involved in the interaction between alpha-chymotrypsin and the inhibitor. When the complex was maleylated, the maleylated chymotrypsin-bound inhibitor was displaced by affinity chromatography on trypsin-Sepharose. Teh recovered derivative was oxidized, subjected to tryptic hydrolysis and the products separated by peptide mapping and analyzed. The peptides were compared with those obtained with non-maleylated inhibitor and fully maleylated free inhibitor. In the fully maleylated inhibitor, the four lysyl residues of the molecule were blocked but in the maleylated chymotrypsin-bound inhibitor, Lys-15 was unmodified in contrast to Lys-26, Lys-41 and Lys-46; therefore Lys-15 is shielded by chymotrypsin in the complex. On the other hand, when inhibitor with a selectively reduced carboxamidomethylated Cys-14-Cys-38 dislufide bridge was allowed to react with chymotrypsin, cleavage occurred not only at Tyr-21, Tyr-35 and Phe-45 but also at Lys-15, cleavage not observed in the case of the fully oxidized inhibitor. This result shows that under particular conditions the bond Lys-15-Ala-16 can be the substrate for chymotrypsin and the side chain of Lys-15 can be inserted in the chymotrypsin specificity pocket. Apparently the contact area of inhibitor with chymotrypsin seems to be similar to that with trypsin [J. Chauvet and R. Acher (1967) J. Biol. Chem. 242, 4274-4275].", "contents": "The reactive sites of Kunitz bovine-trypsin inhibitor. Role of lysine-15 in the interaction with chymotrypsin. Kunitz bovine trypsin inhibitor gave with alpha-chymotrypsin a stoichiometric complex stable at neutral pH. The complex has been characteristized by amino acid composition, molecular sieving and zone electrophoresis. Complete dissociation occurred at pH 4.0 as shown by gel filtration, alpha-Chymotrypsin was displaced from the complex by trypsin either in solution or by affinity chromatography on trypsin-Sepharos: alpha-chymotrypsin was recovered in the filtrate (yield about 100%) and the inhibitor was eluted from trypsin-Sepharose with 0.1 M HCl (yield: 83%). Lysine-15 of the inhibitor was shown to be involved in the interaction between alpha-chymotrypsin and the inhibitor. When the complex was maleylated, the maleylated chymotrypsin-bound inhibitor was displaced by affinity chromatography on trypsin-Sepharose. Teh recovered derivative was oxidized, subjected to tryptic hydrolysis and the products separated by peptide mapping and analyzed. The peptides were compared with those obtained with non-maleylated inhibitor and fully maleylated free inhibitor. In the fully maleylated inhibitor, the four lysyl residues of the molecule were blocked but in the maleylated chymotrypsin-bound inhibitor, Lys-15 was unmodified in contrast to Lys-26, Lys-41 and Lys-46; therefore Lys-15 is shielded by chymotrypsin in the complex. On the other hand, when inhibitor with a selectively reduced carboxamidomethylated Cys-14-Cys-38 dislufide bridge was allowed to react with chymotrypsin, cleavage occurred not only at Tyr-21, Tyr-35 and Phe-45 but also at Lys-15, cleavage not observed in the case of the fully oxidized inhibitor. This result shows that under particular conditions the bond Lys-15-Ala-16 can be the substrate for chymotrypsin and the side chain of Lys-15 can be inserted in the chymotrypsin specificity pocket. Apparently the contact area of inhibitor with chymotrypsin seems to be similar to that with trypsin [J. Chauvet and R. Acher (1967) J. Biol. Chem. 242, 4274-4275]."}
{"id": "PMID:238848", "title": "31P nuclear-magnetic-resonance studies of pyridoxal and pyridoxamine phosphates.  Interaction with cytoplasmic aspartate transaminase.", "content": "The 31P nuclear magnetic resonance (NMR) spectrum of the phosphate in free pyridoxal or pyridoxamine phosphate reveals a resonance signal that is coupled to the methylene protons of the 5-CH2 with JHP of 6.0 +/- 0.3 Hz. Proton noise decoupling results in a single signal with a pH-dependent chemical shift with deprotonation of the phosphate resulting in a shift of the 31P resonance to lower fields. A single 31P NMR signal at a frequency corresponding to fully ionized phosphate monoesters is observed in aspartate-transaminase-bound pyridoxal or pyridoxamine phosphate. The 31P resonance in the holotransaminase is pH-independent and is unaffected by saturating concentrations of substrates or inhibitors. Only denaturation with 6 M guanidine with HCl results in changes in the 31P of the holoenzyme. It appears that the phosphate group of pyridoxal phosphate is bound to a positive pocket in the holoenzyme and remains fully ionized in the pH range of 5.6 to 9.2. The phosphate-binding properties are present even in the apoenzyme which is able to bind inorganic phosphate which then can be displaced by pyridoxal or pyridoxamine phosphate in the process of holoenzyme formation.", "contents": "31P nuclear-magnetic-resonance studies of pyridoxal and pyridoxamine phosphates.  Interaction with cytoplasmic aspartate transaminase. The 31P nuclear magnetic resonance (NMR) spectrum of the phosphate in free pyridoxal or pyridoxamine phosphate reveals a resonance signal that is coupled to the methylene protons of the 5-CH2 with JHP of 6.0 +/- 0.3 Hz. Proton noise decoupling results in a single signal with a pH-dependent chemical shift with deprotonation of the phosphate resulting in a shift of the 31P resonance to lower fields. A single 31P NMR signal at a frequency corresponding to fully ionized phosphate monoesters is observed in aspartate-transaminase-bound pyridoxal or pyridoxamine phosphate. The 31P resonance in the holotransaminase is pH-independent and is unaffected by saturating concentrations of substrates or inhibitors. Only denaturation with 6 M guanidine with HCl results in changes in the 31P of the holoenzyme. It appears that the phosphate group of pyridoxal phosphate is bound to a positive pocket in the holoenzyme and remains fully ionized in the pH range of 5.6 to 9.2. The phosphate-binding properties are present even in the apoenzyme which is able to bind inorganic phosphate which then can be displaced by pyridoxal or pyridoxamine phosphate in the process of holoenzyme formation."}
{"id": "PMID:238849", "title": "Characterization of a specific transport system for arginine in isolated yeast vacuoles.", "content": "The transport of L-arginine was studied in isolated vacuoles of Saccharomyces cerevisiae. A centrifugation method allowed rapid separation of the fragile vacuoles from the incubation media so that initial uptake rates of [14C]arginine could be measured. Labelled arginine added to the medium was accumulated in the isolated vacuoles; it was found to exchange specifically with the arginine already present in the vacuoles. Such an exchange did not take place in intact spheroplasts. The pH dependence of the arginine transport in the vacuoles was tested. As the vacuoles are unstable in the pH range of optimal transport activity (pH above 7.0), the pH optimum of the transport reaction could not be determined. From the temperature dependence, the apparent energy of activation was calculated to be 9800 cal/mol. Arginine transport shows saturation kinetics with an apparent Km of 30 muM in the isolated vacuoles, and of 1.5 muM in the spheroplasts. Competition experiments with amino acids and arginine analogues demonstrated that the arginine transport in both vacuoles and spheroplasts, is highly specific. The two systems, however, were shown to have distinct specificities. The inhibition of vacuolar L-arginine transport by D-arginine, L-histidine, and L-canavanine was competitive with apparent Ki values of 60 muM, 400 muM and 600 muM respectively.", "contents": "Characterization of a specific transport system for arginine in isolated yeast vacuoles. The transport of L-arginine was studied in isolated vacuoles of Saccharomyces cerevisiae. A centrifugation method allowed rapid separation of the fragile vacuoles from the incubation media so that initial uptake rates of [14C]arginine could be measured. Labelled arginine added to the medium was accumulated in the isolated vacuoles; it was found to exchange specifically with the arginine already present in the vacuoles. Such an exchange did not take place in intact spheroplasts. The pH dependence of the arginine transport in the vacuoles was tested. As the vacuoles are unstable in the pH range of optimal transport activity (pH above 7.0), the pH optimum of the transport reaction could not be determined. From the temperature dependence, the apparent energy of activation was calculated to be 9800 cal/mol. Arginine transport shows saturation kinetics with an apparent Km of 30 muM in the isolated vacuoles, and of 1.5 muM in the spheroplasts. Competition experiments with amino acids and arginine analogues demonstrated that the arginine transport in both vacuoles and spheroplasts, is highly specific. The two systems, however, were shown to have distinct specificities. The inhibition of vacuolar L-arginine transport by D-arginine, L-histidine, and L-canavanine was competitive with apparent Ki values of 60 muM, 400 muM and 600 muM respectively."}
{"id": "PMID:238850", "title": "Excretion of trypsin-like activity, electrolytes and protein in mixed and parotid saliva of patients with cystic fibrosis of the pancreas.", "content": "The esterolytic activity of mixed and parotid saliva in cystic fibrosis (CF) patients and normal subjects was determined using BAEE (alpha-Benzoyl-1-arginine-ethylester) as the substrate. Using soybean-trypsin-inhibitor the trypsin-like activity (TLA) was measured and plotted as a function of parotid flow rate. In addition calcium, protein and pH were determined. Trypsin-like activity in mixed and parotid saliva showed large individual variations in CF and normal children. In parotid saliva we could not find any significant difference, whereas a reduction of TLA in mixed saliva of CF patients was observed. The fact that our normal values fell within the range of heterozygotes reported by Rao et al. (19), makes their hypothesis of a close relationship between reduced TLA and the genetic defect very doubtful. Protein, calcium and pH increased with augmented salivation and no difference between CF patients and normal age matched children could be found except for the pH at a flow rate above 0.75 ml/min per m2 body surface where significantly lower pH values resulted. The relevance of reduced TLA to the pathogenesis of cystic fibrosis is discussed.", "contents": "Excretion of trypsin-like activity, electrolytes and protein in mixed and parotid saliva of patients with cystic fibrosis of the pancreas. The esterolytic activity of mixed and parotid saliva in cystic fibrosis (CF) patients and normal subjects was determined using BAEE (alpha-Benzoyl-1-arginine-ethylester) as the substrate. Using soybean-trypsin-inhibitor the trypsin-like activity (TLA) was measured and plotted as a function of parotid flow rate. In addition calcium, protein and pH were determined. Trypsin-like activity in mixed and parotid saliva showed large individual variations in CF and normal children. In parotid saliva we could not find any significant difference, whereas a reduction of TLA in mixed saliva of CF patients was observed. The fact that our normal values fell within the range of heterozygotes reported by Rao et al. (19), makes their hypothesis of a close relationship between reduced TLA and the genetic defect very doubtful. Protein, calcium and pH increased with augmented salivation and no difference between CF patients and normal age matched children could be found except for the pH at a flow rate above 0.75 ml/min per m2 body surface where significantly lower pH values resulted. The relevance of reduced TLA to the pathogenesis of cystic fibrosis is discussed."}
{"id": "PMID:238851", "title": "Effects of aldrin-transdiol on neuromuscular facilitation and depression.", "content": "The effects of aldrin-transdiol, one of the active metabolites of the insecticide dieldrin, on evoked transmitter release, neuromuscular facilitation and neuromuscular depression have been studied in frog sartorius nerve-muscle preparations. Conventional techniques of intracellular recordings were used. Aldrin-transdiol caused a marked increase in end-plate potential amplitude under conditions of low quantal content, i.e., in Mg2+-blocked junctions. The increase in end-plate potential amplitude was less pronounced in curarized junctions, in which the transmitter release was not impaired. Concomitant with the increase in end-plate potential size there was a marked enhancement of facilitation during short trains of stimuli applied to the motor nerve. The decay of facilitation was, however, not seriously affected by aldrin-transdiol. These effects may be explained in terms of the known 'calcium hypothesis' by assuring that aldrin-transdiol increases the amount of calcium which enters the nerve terminal during the nerve impulse. The increase in end-plate potential amplitude and in facilitation by aldrin-transdiol was transient. At later stages of poisoning, end-plate potential and facilitation decreased below control level and neuromuscular depression was significantly enhanced. This latter effect may be the result of a direct inhibitory effect of aldrin-transdiol on transmitter mobilization. As far as the fall in end-plate potential amplitude is concerned the known suppressive action of aldrin-transdiol on the chemical sensitivity of the postsynaptic membrane and on the nerve action potential probably plays a part as well. Finally, neuromuscular transmission was completely blocked by aldrin-transdiol.", "contents": "Effects of aldrin-transdiol on neuromuscular facilitation and depression. The effects of aldrin-transdiol, one of the active metabolites of the insecticide dieldrin, on evoked transmitter release, neuromuscular facilitation and neuromuscular depression have been studied in frog sartorius nerve-muscle preparations. Conventional techniques of intracellular recordings were used. Aldrin-transdiol caused a marked increase in end-plate potential amplitude under conditions of low quantal content, i.e., in Mg2+-blocked junctions. The increase in end-plate potential amplitude was less pronounced in curarized junctions, in which the transmitter release was not impaired. Concomitant with the increase in end-plate potential size there was a marked enhancement of facilitation during short trains of stimuli applied to the motor nerve. The decay of facilitation was, however, not seriously affected by aldrin-transdiol. These effects may be explained in terms of the known 'calcium hypothesis' by assuring that aldrin-transdiol increases the amount of calcium which enters the nerve terminal during the nerve impulse. The increase in end-plate potential amplitude and in facilitation by aldrin-transdiol was transient. At later stages of poisoning, end-plate potential and facilitation decreased below control level and neuromuscular depression was significantly enhanced. This latter effect may be the result of a direct inhibitory effect of aldrin-transdiol on transmitter mobilization. As far as the fall in end-plate potential amplitude is concerned the known suppressive action of aldrin-transdiol on the chemical sensitivity of the postsynaptic membrane and on the nerve action potential probably plays a part as well. Finally, neuromuscular transmission was completely blocked by aldrin-transdiol."}
{"id": "PMID:238852", "title": "Effects of psychotropic drugs on methamphetamine-induced behavioral excitation in grouped mice.", "content": "When 7 mice injected with methamphetamine (5 mg/kg, s.c.) were placed together into a box with a limited space maintained at 28-30 degrees C, the grouped mice showed extreme behavioral excitation consisting of 2 typical features: fighting behavior with squeak and hyperactive behavior characterized by running and jumping. The effects of various drugs tested, according to the minimal effective doses (mg/kg, p.o.) which inhibited fighting behavior and hyperactive behavior respectively, were: haloperidol, 0.1 (fighting)--0.25 (hyperactivity); clothiapine, 1 - 1; perphenazine, 1 - 1; thiothixene, 1 - 5; chlorpromazine, 5 - 10; diazepam, 5 - 100; reserpine, 100 - 100; phenoxybenzamine, 200 - 200 (no effect). Major tranquilizers except rauwolfia alkaloids completely inhibited both types of excited behavior at low doses, as compared with the taming effects of the drugs on footshock-induced fighting episodes in pairs of mice. On the other hand, minor tranquilizers suppressed only fighting behavior, showing little effect on hyperactive behavior. None of the antidepressants, adrenergic blocking agents and other drugs showed antagonism to both types of excited behavior. The results indicate that this method may be useful for the evaluation of psychotropic drug effects in grouped mice.", "contents": "Effects of psychotropic drugs on methamphetamine-induced behavioral excitation in grouped mice. When 7 mice injected with methamphetamine (5 mg/kg, s.c.) were placed together into a box with a limited space maintained at 28-30 degrees C, the grouped mice showed extreme behavioral excitation consisting of 2 typical features: fighting behavior with squeak and hyperactive behavior characterized by running and jumping. The effects of various drugs tested, according to the minimal effective doses (mg/kg, p.o.) which inhibited fighting behavior and hyperactive behavior respectively, were: haloperidol, 0.1 (fighting)--0.25 (hyperactivity); clothiapine, 1 - 1; perphenazine, 1 - 1; thiothixene, 1 - 5; chlorpromazine, 5 - 10; diazepam, 5 - 100; reserpine, 100 - 100; phenoxybenzamine, 200 - 200 (no effect). Major tranquilizers except rauwolfia alkaloids completely inhibited both types of excited behavior at low doses, as compared with the taming effects of the drugs on footshock-induced fighting episodes in pairs of mice. On the other hand, minor tranquilizers suppressed only fighting behavior, showing little effect on hyperactive behavior. None of the antidepressants, adrenergic blocking agents and other drugs showed antagonism to both types of excited behavior. The results indicate that this method may be useful for the evaluation of psychotropic drug effects in grouped mice."}
{"id": "PMID:238853", "title": "Beta-adrenergic blockade and atrio--ventricular conduction impairment.", "content": "Atrio--ventricular conduction and its modifications induced by six Beta-adrenergic blocking agents have been investigated in the dog. Premature atrial stimuli (St2) were applied at variable intervals following regular stimuli (St1) ensuring atrial pacing; atrial (AERP), nodoventricular (NERP) and global (GERP) effective refractory periods as well as global functional refractory period (GFRP) were determined before and after administration of each of the six drugs. When Beta-blockade was produced with d,1-propranolol which hwas membrane stabilizing effects (MSE) but no intrinsic sympathomimetic activity (ISA) or with sotalol, which has neither MSE nor ISA, all parameters were significantly increased. When Beta-blockade was achieved with pindolol or practolol, which have only a poor Beta-adrenolytic potency and no ISA. Alprenolol showed intermediate effects. Thus, it appears that Beta-blockade and not MSE, is responsible for the onset of A-V conduction impairment but that ISA, probably through a metabolic mechanism, affords protection against this impairment. On the other hand, measurement of ventricular effective refractory period (VERP) has shown that at the Purkinje-free junction, it is MSE which is mainly involved in conduction impairment.", "contents": "Beta-adrenergic blockade and atrio--ventricular conduction impairment. Atrio--ventricular conduction and its modifications induced by six Beta-adrenergic blocking agents have been investigated in the dog. Premature atrial stimuli (St2) were applied at variable intervals following regular stimuli (St1) ensuring atrial pacing; atrial (AERP), nodoventricular (NERP) and global (GERP) effective refractory periods as well as global functional refractory period (GFRP) were determined before and after administration of each of the six drugs. When Beta-blockade was produced with d,1-propranolol which hwas membrane stabilizing effects (MSE) but no intrinsic sympathomimetic activity (ISA) or with sotalol, which has neither MSE nor ISA, all parameters were significantly increased. When Beta-blockade was achieved with pindolol or practolol, which have only a poor Beta-adrenolytic potency and no ISA. Alprenolol showed intermediate effects. Thus, it appears that Beta-blockade and not MSE, is responsible for the onset of A-V conduction impairment but that ISA, probably through a metabolic mechanism, affords protection against this impairment. On the other hand, measurement of ventricular effective refractory period (VERP) has shown that at the Purkinje-free junction, it is MSE which is mainly involved in conduction impairment."}
{"id": "PMID:238854", "title": "Control of peripheral vascular resistance in perfused hindquarters of dogs: lack of effect of nicotinic and muscarinic ganglion block.", "content": "The effects of nicotinic and muscarinic ganglion blockade were studied on the peripheral resistance of the perfused hindlimbs of the dog. Nicotinic ganglion blockade by chlorisondamine (1 mg/kg) significantly reduced reflex vasomotor responses but did not significantly alter hindlimb peripheral resistance. Combined nicotinic ganglion blockade by chlorisondamine (1 mg/kg) and muscarinic ganglion blockade by atropine (50mug/kg) abolished the reflex vasomotor response but did not alter hindlimb peripheral resistance. It was concluded that autoregulatory mechanisms are capable of maintaining a peripheral resistance after block of both muscarinic and nicotinic ganglion transmission.", "contents": "Control of peripheral vascular resistance in perfused hindquarters of dogs: lack of effect of nicotinic and muscarinic ganglion block. The effects of nicotinic and muscarinic ganglion blockade were studied on the peripheral resistance of the perfused hindlimbs of the dog. Nicotinic ganglion blockade by chlorisondamine (1 mg/kg) significantly reduced reflex vasomotor responses but did not significantly alter hindlimb peripheral resistance. Combined nicotinic ganglion blockade by chlorisondamine (1 mg/kg) and muscarinic ganglion blockade by atropine (50mug/kg) abolished the reflex vasomotor response but did not alter hindlimb peripheral resistance. It was concluded that autoregulatory mechanisms are capable of maintaining a peripheral resistance after block of both muscarinic and nicotinic ganglion transmission."}
{"id": "PMID:238855", "title": "Antinociceptive action of oxotremorine and regional turnover of rat brain noradrenaline, dopamine and 5-HT.", "content": "In the rat, oxotremorine increases the threshold for vocalisation after-discharge (affective component of pain reactions) dose dependently at subtremor doses (30-67 mug/kg s.c.). Doses of 225-506 mug/kg were needed to elevate the thresholds for vocalisation and motor response. 1-Tryptophan, PCPA, alpha-methyl-p-tyrosine, 1-Dopa, pimozide and LSD-25 did not affect the antinociceptive activity of oxotremorine, while phenocybenzamine slightly increased the threshold for vocalisation. Oxotremorine did not change the endogenous brain concentrations of noradrenaline and dopamine or 5-HT but decreased that of 5-HIAA in all brain regions at the time of maximal analgesia. The decrease of 5-HIAA was still present after pretreatment with probenecid. After inhibition of tyrosine hydroxylase, oxotremorine accelerated the depletion of dopamine in telencephalic cortex during maximal antinociceptive activity and of noradrenaline in all brain regions at a time when this activity had vanished. Atropine significantly antagonized the analgesic activity of oxotremorine. It is concluded that oxotremorine antinociceptive activity in the rat is related to a cholinergic compoent, while a monoaminergic component is not directly involved.", "contents": "Antinociceptive action of oxotremorine and regional turnover of rat brain noradrenaline, dopamine and 5-HT. In the rat, oxotremorine increases the threshold for vocalisation after-discharge (affective component of pain reactions) dose dependently at subtremor doses (30-67 mug/kg s.c.). Doses of 225-506 mug/kg were needed to elevate the thresholds for vocalisation and motor response. 1-Tryptophan, PCPA, alpha-methyl-p-tyrosine, 1-Dopa, pimozide and LSD-25 did not affect the antinociceptive activity of oxotremorine, while phenocybenzamine slightly increased the threshold for vocalisation. Oxotremorine did not change the endogenous brain concentrations of noradrenaline and dopamine or 5-HT but decreased that of 5-HIAA in all brain regions at the time of maximal analgesia. The decrease of 5-HIAA was still present after pretreatment with probenecid. After inhibition of tyrosine hydroxylase, oxotremorine accelerated the depletion of dopamine in telencephalic cortex during maximal antinociceptive activity and of noradrenaline in all brain regions at a time when this activity had vanished. Atropine significantly antagonized the analgesic activity of oxotremorine. It is concluded that oxotremorine antinociceptive activity in the rat is related to a cholinergic compoent, while a monoaminergic component is not directly involved."}
{"id": "PMID:238856", "title": "The effect of penfluridol and some psychotropic drugs on monoamine metabolism in central nervous system.", "content": "Five neuroleptics: penfluridol, haloperidol, chlorpromazine, pimozide and oxypertine, and two benzodiazepine minor tranquilizers; chlordiazepoxide and diazepam, were studied in mice and rats. When the drugs were injected i.p. in mice, all neuroleptics increased the brain homovanillic acid (HVA) concentration but two benzodiazepines did not change it. Of the drugs tested, only pimozide increased the brain level of 5-hydroxyindoleacetic acid. Penfluridol accelerated the turnover rate of brain dopamine (DA), wheras haloperidol accelerated both DA and noradrenaline turnover rates. In rats, oral administration of penfluridol caused an increase in the striatal HVA and 3,4-dihydroxyphenylacetic acid which persisted longer than that following haloperidol. The concentration of brain 3-methoxy-4-hydroxyphenylethylene glycol, however, was not affected by penfluridol even when the drug was administered at a high dose. Based on these and earlier findings, it is concluded that the effect of penfluridol on DA metabolism resembles that of typical neuroleptic compounds and penfluridol acts only on DA neurons as a long-acting DA receptor blocker.", "contents": "The effect of penfluridol and some psychotropic drugs on monoamine metabolism in central nervous system. Five neuroleptics: penfluridol, haloperidol, chlorpromazine, pimozide and oxypertine, and two benzodiazepine minor tranquilizers; chlordiazepoxide and diazepam, were studied in mice and rats. When the drugs were injected i.p. in mice, all neuroleptics increased the brain homovanillic acid (HVA) concentration but two benzodiazepines did not change it. Of the drugs tested, only pimozide increased the brain level of 5-hydroxyindoleacetic acid. Penfluridol accelerated the turnover rate of brain dopamine (DA), wheras haloperidol accelerated both DA and noradrenaline turnover rates. In rats, oral administration of penfluridol caused an increase in the striatal HVA and 3,4-dihydroxyphenylacetic acid which persisted longer than that following haloperidol. The concentration of brain 3-methoxy-4-hydroxyphenylethylene glycol, however, was not affected by penfluridol even when the drug was administered at a high dose. Based on these and earlier findings, it is concluded that the effect of penfluridol on DA metabolism resembles that of typical neuroleptic compounds and penfluridol acts only on DA neurons as a long-acting DA receptor blocker."}
{"id": "PMID:238857", "title": "Effects of some adrenergic and cholinergic drugs on isolated spleen strips from the cod, Gadus morhua.", "content": "The effects of drugs on isolated spleen strips from the cod, Gadus morhua, have been investigated. Affinities and intrinsic activities for various agonists were determined from cumulative dose-response curves. Contractions were produced by acetylcholine, methacholine or carbachol. The response to acetylcholine was considerably potentiated by the acetylcholinesterase inhibitor BW 284 C51. Methacholine-induced responses were competitively blocked by atropine (pA2 = 8.2), indicating the presence of muscarinic receptors. Nicotine did not contract the spleen strips. Adrenaline, noradrenaline or phenylephrine contracted the preparations and so did isoprenaline in high concentrations. Competitive blockade of the noradrenaline-induced contraction was obtained with yohimbine (pA2 = 6.1), phentolamine (pA2 = 6.0) and propranolol (pA2 = 3.4), and non-competitive blockade with phenoxybenzamine (pM50 = 7.0), indicating that alpha-adrenoceptors mediate the contractions produced by the adrenergic agonists. Isoprenaline caused a slight relaxation of preparations precontracted with methacholine. This effect was abolished by propranolol suggesting the presence of beta-adrenoceptors. Judged from the pA-values for the competitive antagonist, arterial and capsular/trabecular smooth muscles have slightly different alpha-adrenoceptor properties.", "contents": "Effects of some adrenergic and cholinergic drugs on isolated spleen strips from the cod, Gadus morhua. The effects of drugs on isolated spleen strips from the cod, Gadus morhua, have been investigated. Affinities and intrinsic activities for various agonists were determined from cumulative dose-response curves. Contractions were produced by acetylcholine, methacholine or carbachol. The response to acetylcholine was considerably potentiated by the acetylcholinesterase inhibitor BW 284 C51. Methacholine-induced responses were competitively blocked by atropine (pA2 = 8.2), indicating the presence of muscarinic receptors. Nicotine did not contract the spleen strips. Adrenaline, noradrenaline or phenylephrine contracted the preparations and so did isoprenaline in high concentrations. Competitive blockade of the noradrenaline-induced contraction was obtained with yohimbine (pA2 = 6.1), phentolamine (pA2 = 6.0) and propranolol (pA2 = 3.4), and non-competitive blockade with phenoxybenzamine (pM50 = 7.0), indicating that alpha-adrenoceptors mediate the contractions produced by the adrenergic agonists. Isoprenaline caused a slight relaxation of preparations precontracted with methacholine. This effect was abolished by propranolol suggesting the presence of beta-adrenoceptors. Judged from the pA-values for the competitive antagonist, arterial and capsular/trabecular smooth muscles have slightly different alpha-adrenoceptor properties."}
{"id": "PMID:238862", "title": "Rates of onset and offset of action of narcotic analgesics in isolated preparations.", "content": "In isolated preparations of the myenteric plexus--longitudinal muscle of the guinea-pig ileum and the mouse vas deferens, the rates of onset and offset of action of narcotic analgesics are inversely related to lipid solubility; this effect is probably due to drug binding at secondary lipid-rich binding sites. These findings are in contrast to observations in vivo by A. Herz and his colleagues, who showed that the rates of onset of action and of recovery are directly related to lipid solubility because of the presence of lipid-rich barriers. In view of the opposite effects, an optimum may be expected when a drug has a degree of lipid solubility which ensures rapid penetration of the blood--brain barrier without seriously slowing down of receptor association and dissociation. From the interaction of rapidly acting quaternary antagonists, e.g. N-methylnalorphinium, with slowly acting agonists, e.g. methadone, it is concluded that at least a part of the receptor site is on the surface of the cell membrane, and the possibility of an allosteric agonist--antagonist interaction is considered.", "contents": "Rates of onset and offset of action of narcotic analgesics in isolated preparations. In isolated preparations of the myenteric plexus--longitudinal muscle of the guinea-pig ileum and the mouse vas deferens, the rates of onset and offset of action of narcotic analgesics are inversely related to lipid solubility; this effect is probably due to drug binding at secondary lipid-rich binding sites. These findings are in contrast to observations in vivo by A. Herz and his colleagues, who showed that the rates of onset of action and of recovery are directly related to lipid solubility because of the presence of lipid-rich barriers. In view of the opposite effects, an optimum may be expected when a drug has a degree of lipid solubility which ensures rapid penetration of the blood--brain barrier without seriously slowing down of receptor association and dissociation. From the interaction of rapidly acting quaternary antagonists, e.g. N-methylnalorphinium, with slowly acting agonists, e.g. methadone, it is concluded that at least a part of the receptor site is on the surface of the cell membrane, and the possibility of an allosteric agonist--antagonist interaction is considered."}
{"id": "PMID:238863", "title": "Actions of bile salts and of papaverine and intracellular cyclic AMP in isolated rat uterus.", "content": "Both antioxytocin and antiphosphodiesterase activities of desoxycholate were potentiated by lowering the pH of the medium. The results suggest the possibility that it is the bile salt in the non-ionized form which exerts the antioxytocin and antiphosphodiesterase action. The concentration of tissue cyclic AMP was measured at different times during relaxation of the uterus. The results show a significant increase in tissue cyclic AMP concentration at a time when the muscle was just beginning to relax in response to papaverine, but not in response to chenodesoxycholate. The intracellular level of cyclic AMP during relaxation of the uterus produced by papaverine or chenodesoxycholate was, however, significantly increased when relaxation was about 90% complete. The difference between the mode of action of papaverine and that of the bile salts is discussed.", "contents": "Actions of bile salts and of papaverine and intracellular cyclic AMP in isolated rat uterus. Both antioxytocin and antiphosphodiesterase activities of desoxycholate were potentiated by lowering the pH of the medium. The results suggest the possibility that it is the bile salt in the non-ionized form which exerts the antioxytocin and antiphosphodiesterase action. The concentration of tissue cyclic AMP was measured at different times during relaxation of the uterus. The results show a significant increase in tissue cyclic AMP concentration at a time when the muscle was just beginning to relax in response to papaverine, but not in response to chenodesoxycholate. The intracellular level of cyclic AMP during relaxation of the uterus produced by papaverine or chenodesoxycholate was, however, significantly increased when relaxation was about 90% complete. The difference between the mode of action of papaverine and that of the bile salts is discussed."}
{"id": "PMID:238859", "title": "Antagonism by propranolol of the ganglion stimulant action of 5-hydroxytryptamine.", "content": "The effects of racemic propranolol and its constituent isomers were studied on ganglionic stimulation produced in situ by close arterial injection of 5-HT and DMPP to the superior cervical ganglion. Ganglion stimulation was recorded in terms of the resultant contraction of the nictitating membrane. d,l-Propranolol caused a biphasic antagonism of the ganglion stimulant effect of 5-HT. At low doses, 0.5-10 mug, the antagonism was surmountable by increasing the amount of 5-HT. The l-isomer (0.2-4 mug) but not d-propranolol also caused antagonism. At higher doses, 0.1-5 mg, both d,l- and d-propranolol caused a second type of blockade of 5-HT which was not surmountable and resembled that seen with procaine. The ganglion stimulant effects of DMPP and acetylcholine were only antagonised by the higher doses of d- and d,l-propranolol. d,l-Propranolol did not reduce the direct stimulation by 5-HT on the muscle of the nictitating membrane.", "contents": "Antagonism by propranolol of the ganglion stimulant action of 5-hydroxytryptamine. The effects of racemic propranolol and its constituent isomers were studied on ganglionic stimulation produced in situ by close arterial injection of 5-HT and DMPP to the superior cervical ganglion. Ganglion stimulation was recorded in terms of the resultant contraction of the nictitating membrane. d,l-Propranolol caused a biphasic antagonism of the ganglion stimulant effect of 5-HT. At low doses, 0.5-10 mug, the antagonism was surmountable by increasing the amount of 5-HT. The l-isomer (0.2-4 mug) but not d-propranolol also caused antagonism. At higher doses, 0.1-5 mg, both d,l- and d-propranolol caused a second type of blockade of 5-HT which was not surmountable and resembled that seen with procaine. The ganglion stimulant effects of DMPP and acetylcholine were only antagonised by the higher doses of d- and d,l-propranolol. d,l-Propranolol did not reduce the direct stimulation by 5-HT on the muscle of the nictitating membrane."}
{"id": "PMID:238864", "title": "Effect of benzodiazepine compounds on brain amine metabolism.", "content": "In mice, chlordiazepoxide, diazepam and flurazepam reduced 5-HT synthesis and metabolism in the teldiencephalon following an i.v. injection of 3H-tryptophan. Only diazepam produced a significant effect in the brainstem. The steady state level of brain 5-HT or of tryptophan was not altered by any of the drugs. Chlordiazepoxide and diazepam, but not flurazepam, decreased the rate of norepinephrine loss from the brain following inhibition of synthesis with alpha-methyltyrosine.", "contents": "Effect of benzodiazepine compounds on brain amine metabolism. In mice, chlordiazepoxide, diazepam and flurazepam reduced 5-HT synthesis and metabolism in the teldiencephalon following an i.v. injection of 3H-tryptophan. Only diazepam produced a significant effect in the brainstem. The steady state level of brain 5-HT or of tryptophan was not altered by any of the drugs. Chlordiazepoxide and diazepam, but not flurazepam, decreased the rate of norepinephrine loss from the brain following inhibition of synthesis with alpha-methyltyrosine."}
{"id": "PMID:238860", "title": "Attenuation of hydrochlorothiazide-induced hypokalemia in dogs by a beta-adrenergic blocking drug, timolol.", "content": "Hydrochlorothiazide, administered at 1, 3 and 9 mg/kg/day p.o. for 4 days, produced a dose-dependent lowering of plasma potassium and an elevation in plasma renin activity in unanesthetized dogs. When plasma renin activity was suppressed in diuretic-treated dogs by the potent beta-adrenergic receptor-blocking drug, timolol (0.5, 2 mg/kg/day p.o. for 4 days), the hypokalemia and hyperreninemia were significantly less pronounced. The data suggest that beta-adrenergic blocking drugs can be used to antagonize these side effects of diuretics.", "contents": "Attenuation of hydrochlorothiazide-induced hypokalemia in dogs by a beta-adrenergic blocking drug, timolol. Hydrochlorothiazide, administered at 1, 3 and 9 mg/kg/day p.o. for 4 days, produced a dose-dependent lowering of plasma potassium and an elevation in plasma renin activity in unanesthetized dogs. When plasma renin activity was suppressed in diuretic-treated dogs by the potent beta-adrenergic receptor-blocking drug, timolol (0.5, 2 mg/kg/day p.o. for 4 days), the hypokalemia and hyperreninemia were significantly less pronounced. The data suggest that beta-adrenergic blocking drugs can be used to antagonize these side effects of diuretics."}
{"id": "PMID:238865", "title": "Stereospecific morphine adsorption to phosphatidyl serine and other membranous components of brain.", "content": "In the course of investigating various membranous components for morphine binding, it was found that the major substance responsible was phosphatidyl serine. Other acidic lipids, such as phosphatidic acid and phosphoinositides bind to a considerably lesser extent, while neutral lipids, glycolipids and other phosphatides bind slightly or not at all. Total lipid extracts from a number of regions of rat brain exhibited different degrees of binding to (-)-morphine, such regions as the cerebral cortex and thalamus being the greatest. From an examination of the pH curve for binding and the effect of ionic strength, it was concluded that the binging was largely electrostatic. The method employed was the radioactive measurement of 14C-morphine adsorption to surface films of phosphatidyl serine. When the phosphatide was dispersed in a nonionic detergent near the critical micelle concentration, adsorption was maximal, attaining a value of 1 molecule of morphine adsorbed per molecule of phosphatidyl serine in the surface micelle. The relation between binding affinity and biological potency was not consistent. Morphine adsorption occurred with films prepared from a dispersion of the phosphatide and a hydrophobic protein from synaptic membranes. With the use of levorphanol and dextrorphan it could be shown that binding of morphine was stereospecific.", "contents": "Stereospecific morphine adsorption to phosphatidyl serine and other membranous components of brain. In the course of investigating various membranous components for morphine binding, it was found that the major substance responsible was phosphatidyl serine. Other acidic lipids, such as phosphatidic acid and phosphoinositides bind to a considerably lesser extent, while neutral lipids, glycolipids and other phosphatides bind slightly or not at all. Total lipid extracts from a number of regions of rat brain exhibited different degrees of binding to (-)-morphine, such regions as the cerebral cortex and thalamus being the greatest. From an examination of the pH curve for binding and the effect of ionic strength, it was concluded that the binging was largely electrostatic. The method employed was the radioactive measurement of 14C-morphine adsorption to surface films of phosphatidyl serine. When the phosphatide was dispersed in a nonionic detergent near the critical micelle concentration, adsorption was maximal, attaining a value of 1 molecule of morphine adsorbed per molecule of phosphatidyl serine in the surface micelle. The relation between binding affinity and biological potency was not consistent. Morphine adsorption occurred with films prepared from a dispersion of the phosphatide and a hydrophobic protein from synaptic membranes. With the use of levorphanol and dextrorphan it could be shown that binding of morphine was stereospecific."}
{"id": "PMID:238861", "title": "Reduction of adverse acute cardiovascular actions of 6-hydroxydopamine in dogs by adrenergic receptor blockade.", "content": "Injection of dogs with 50 mg/kg of 6-hydroxydopamine (6-OHDA) caused large increases in blood pressure and heart rate, followed after 1 or 2 hr by severe hypotension. Prior administration of the adrenergic receptor blocking agents phentolamine and propranolol attenuated both the hyper- and hypotensive phases of 6-OHDA. Phentolamine and propranolol did not prevent depletionof norepinephrine or development of the characteristic morphological changes induced in adrenergic fibers by 6-OHDA.", "contents": "Reduction of adverse acute cardiovascular actions of 6-hydroxydopamine in dogs by adrenergic receptor blockade. Injection of dogs with 50 mg/kg of 6-hydroxydopamine (6-OHDA) caused large increases in blood pressure and heart rate, followed after 1 or 2 hr by severe hypotension. Prior administration of the adrenergic receptor blocking agents phentolamine and propranolol attenuated both the hyper- and hypotensive phases of 6-OHDA. Phentolamine and propranolol did not prevent depletionof norepinephrine or development of the characteristic morphological changes induced in adrenergic fibers by 6-OHDA."}
{"id": "PMID:238866", "title": "Effect of graft-versus-host reaction on the immune response to alloantigens and growth of a syngeneic tumor.", "content": "The graft-versus-host reaction (GVHR) was evoked in (C57BL/6J times C3H/6J times DBA/2J) F1 hybrids by grafting parental lymphoid cells. Groups of bothe F1 hybrids were immunized with thymocytes carrying Thy-1.1 (theta AKR) antigen and still other groups of (C57BL/6J times C3H/HeJ) F1 hybrids were immunized with thymocytes carrying the H-2-d antigen. Plaque-forming cells (PFC) producing antibodies to the Thy-1.1 antigen, lytic for AKR thymocytes, or antibodies to the H-2-d antigen, lytic for lymphoblasts carrying the H-2-d antigens, were enumerated in spleens of experimental animals. A pronounced suppression of the immune response to the Thy-1.1 antigen was found in animals suffering from GVHR. The suppression could be demonstrated in some animals as late as 180 days after the onset of GVHR. Significant, although less pronounced suppression was found when response to the H-2-d antigens was assayed. After grafting 10-3 or 10-4 DBA/2J derived lymphoma cells (L5178Y) into (C57BL/6J times DBA/2J) F1 hybrids, clinically detectable tumor growth was found earlier and more frequently in hybrids suffering from GVHR than in control animals. The results obtained lend support to the concept that immunosuppression accompanying GVHR may influence the formation and/or growth of the malignant tumors. In addition, a synergistic effect in the suppression of the responsiveness of F1 recipients was seen in some instances when a mixture of parental bone marrow and thymus cells was grafted. The results are consistent with data indicating that more than one cell type is involved in the initiation of GVHR.", "contents": "Effect of graft-versus-host reaction on the immune response to alloantigens and growth of a syngeneic tumor. The graft-versus-host reaction (GVHR) was evoked in (C57BL/6J times C3H/6J times DBA/2J) F1 hybrids by grafting parental lymphoid cells. Groups of bothe F1 hybrids were immunized with thymocytes carrying Thy-1.1 (theta AKR) antigen and still other groups of (C57BL/6J times C3H/HeJ) F1 hybrids were immunized with thymocytes carrying the H-2-d antigen. Plaque-forming cells (PFC) producing antibodies to the Thy-1.1 antigen, lytic for AKR thymocytes, or antibodies to the H-2-d antigen, lytic for lymphoblasts carrying the H-2-d antigens, were enumerated in spleens of experimental animals. A pronounced suppression of the immune response to the Thy-1.1 antigen was found in animals suffering from GVHR. The suppression could be demonstrated in some animals as late as 180 days after the onset of GVHR. Significant, although less pronounced suppression was found when response to the H-2-d antigens was assayed. After grafting 10-3 or 10-4 DBA/2J derived lymphoma cells (L5178Y) into (C57BL/6J times DBA/2J) F1 hybrids, clinically detectable tumor growth was found earlier and more frequently in hybrids suffering from GVHR than in control animals. The results obtained lend support to the concept that immunosuppression accompanying GVHR may influence the formation and/or growth of the malignant tumors. In addition, a synergistic effect in the suppression of the responsiveness of F1 recipients was seen in some instances when a mixture of parental bone marrow and thymus cells was grafted. The results are consistent with data indicating that more than one cell type is involved in the initiation of GVHR."}
{"id": "PMID:238867", "title": "Psychophysical evaluation of toxic effects on sensory systems.", "content": "Toxic effects on sensory systems have rarely been evaluated by psychophysical methods. As examples of possible applications four studies are described. Sodium salicylate and kanamycin, both reported to produce hearing deficits in man, have also been demonstrated to affect auditory thresholds in monkeys. With the latter drug the deficits measured were found to be correlated with specific loss of receptor cells in the cochlea. Pheniprazine, known to induce red-green color blindness, was found to disrupt a wavelength discrimination in pigeons. Trans 11-amino-10,11-dihydro-5-(3-dimethylaminopropyl)-5,10-expoxy-5H-dibenzo[a,d]-cycloheptene dihydrochloride, which was found to bleach the tapidum lucidum in dogs when given subacutely, was found to decrease sensitivity to light. The loss in sensitivity measured by behavioral techniques was correlated with the loss of coloration of the tapidum. Monkeys, not having a tapidum, did not show a similar effect.", "contents": "Psychophysical evaluation of toxic effects on sensory systems. Toxic effects on sensory systems have rarely been evaluated by psychophysical methods. As examples of possible applications four studies are described. Sodium salicylate and kanamycin, both reported to produce hearing deficits in man, have also been demonstrated to affect auditory thresholds in monkeys. With the latter drug the deficits measured were found to be correlated with specific loss of receptor cells in the cochlea. Pheniprazine, known to induce red-green color blindness, was found to disrupt a wavelength discrimination in pigeons. Trans 11-amino-10,11-dihydro-5-(3-dimethylaminopropyl)-5,10-expoxy-5H-dibenzo[a,d]-cycloheptene dihydrochloride, which was found to bleach the tapidum lucidum in dogs when given subacutely, was found to decrease sensitivity to light. The loss in sensitivity measured by behavioral techniques was correlated with the loss of coloration of the tapidum. Monkeys, not having a tapidum, did not show a similar effect."}
{"id": "PMID:238858", "title": "Evidence for the involvement of alpha-adrenoceptor blockade in the antihypertensive action of diazoxide in the renal hypertensive rat.", "content": "The effects of diazoxide on the blood pressure and heart rate of conscious renal hypertensive rats have been investigated. The antihypertensive action of diazoxide has been studied in relation to the effects of diazoxide pretreatment on pressor responses to stimulation of the complete sympathetic outflow and to injections of noradrenaline, phenylephrine, angiotensin and serotonin in pithed rats. In pithed preparations, pressor responses to sympathetic nerve stimulation, and to injected noradrenaline and phenylephrine were significantly reduced by diazoxide pretreatment, at a time corresponding to maximal reduction of blood pressure in conscious animals. At this time there was no significant reduction of pressor responses to injected angiotensin or serotonin. These findings suggest a contribution of alpha-adrenoceptor blockade to the antihypertensive activity of diazoxide.", "contents": "Evidence for the involvement of alpha-adrenoceptor blockade in the antihypertensive action of diazoxide in the renal hypertensive rat. The effects of diazoxide on the blood pressure and heart rate of conscious renal hypertensive rats have been investigated. The antihypertensive action of diazoxide has been studied in relation to the effects of diazoxide pretreatment on pressor responses to stimulation of the complete sympathetic outflow and to injections of noradrenaline, phenylephrine, angiotensin and serotonin in pithed rats. In pithed preparations, pressor responses to sympathetic nerve stimulation, and to injected noradrenaline and phenylephrine were significantly reduced by diazoxide pretreatment, at a time corresponding to maximal reduction of blood pressure in conscious animals. At this time there was no significant reduction of pressor responses to injected angiotensin or serotonin. These findings suggest a contribution of alpha-adrenoceptor blockade to the antihypertensive activity of diazoxide."}
{"id": "PMID:238868", "title": "Determinants of drug effects on punished responding.", "content": "The effects of drugs on punished responding depend on interactions among a large number of experimental variables. Among these variables are the drug history of the animal, the dose of the drug administered, the type of stimulus used to punish responding,  the intensity and duration of the punishing stimulus, the schedule of presentation of the punishing stimulus, the control rate and pattern of punished responding, the schedule of positive reinforcement maintaining the punished responding, the species of animal, the deprivation state of the animal, the behavioral history of the animal, and the nature of the required response. Although it is not known how all of these variables interact to determine the effect of drugs on punished responding, there is evidence that many of these variables are important as determinants of drug effects. The task facing behavioral pharmacologists studying drug effects on punished responding is to determine under what conditions drugs produce their characteristic effects on punished responding.", "contents": "Determinants of drug effects on punished responding. The effects of drugs on punished responding depend on interactions among a large number of experimental variables. Among these variables are the drug history of the animal, the dose of the drug administered, the type of stimulus used to punish responding,  the intensity and duration of the punishing stimulus, the schedule of presentation of the punishing stimulus, the control rate and pattern of punished responding, the schedule of positive reinforcement maintaining the punished responding, the species of animal, the deprivation state of the animal, the behavioral history of the animal, and the nature of the required response. Although it is not known how all of these variables interact to determine the effect of drugs on punished responding, there is evidence that many of these variables are important as determinants of drug effects. The task facing behavioral pharmacologists studying drug effects on punished responding is to determine under what conditions drugs produce their characteristic effects on punished responding."}
{"id": "PMID:238869", "title": "Reinforcement schedules and extrapolations to humans from animals in behavioral pharmacology.", "content": "Behavior controlled by various schedules of reinforcement is useful for characterizing drugs as well as for analyzing the mechanisms of action of their effects on behavior. Conditioned avoidance techniques have been useful for studying neuroleptics and for predicting their clinical antipsychotic acitivity; the possible involvement of dopaminergic mechanisms in the effect of neurolpetics on avoidance behavior is discussed. Tricyclic antidepressant agents have been studied in assays involving interactions with other agents, such  as cocaine, amphetamine and tetrabenazine. One type of operant behavior, Sidman avoidance, has been used as particularly sensitive assay for such drug interactions. Another schedule, in which \"observing\" responses in pigeons are measured. seems to provide a method for studying antidepressants without involving drug interaction phenomena. For tricyclic compounds, facilitation of observing responses and weak potency of conditioned avoidance inhibition constitute a pharmacological profile that seems to have some predictive value for clinical imipramine-like antidepressant activity. \"Conflict (punishment) schedules have been useful for predicting antianxiety activity in man. Although the degree of anticonflict effect observed is consistent with Dew's rate dependency hypothesis, this principle does not fully account for the observed drug effects. In the conflict model, the actions of benzodiazepines differ in drug-naive versus drug-experienced animals. Experiments with parachlorophenylalnine have not yet provided clear support for the postulated role of serotonin in related phenomena.", "contents": "Reinforcement schedules and extrapolations to humans from animals in behavioral pharmacology. Behavior controlled by various schedules of reinforcement is useful for characterizing drugs as well as for analyzing the mechanisms of action of their effects on behavior. Conditioned avoidance techniques have been useful for studying neuroleptics and for predicting their clinical antipsychotic acitivity; the possible involvement of dopaminergic mechanisms in the effect of neurolpetics on avoidance behavior is discussed. Tricyclic antidepressant agents have been studied in assays involving interactions with other agents, such  as cocaine, amphetamine and tetrabenazine. One type of operant behavior, Sidman avoidance, has been used as particularly sensitive assay for such drug interactions. Another schedule, in which \"observing\" responses in pigeons are measured. seems to provide a method for studying antidepressants without involving drug interaction phenomena. For tricyclic compounds, facilitation of observing responses and weak potency of conditioned avoidance inhibition constitute a pharmacological profile that seems to have some predictive value for clinical imipramine-like antidepressant activity. \"Conflict (punishment) schedules have been useful for predicting antianxiety activity in man. Although the degree of anticonflict effect observed is consistent with Dew's rate dependency hypothesis, this principle does not fully account for the observed drug effects. In the conflict model, the actions of benzodiazepines differ in drug-naive versus drug-experienced animals. Experiments with parachlorophenylalnine have not yet provided clear support for the postulated role of serotonin in related phenomena."}
{"id": "PMID:238870", "title": "Androgen biosynthesis in experimental cryptorchidism.", "content": "This study was conducted to investigate the effects of unilateral cryptorchidism on androgen production and testicular maturation. Experimental cryptorchidism was produced in small and large prepuberal guinea pigs by forcing the testis to remain in the abdomen for a period of 30 days. Small prepuberal animals, which did not reach sexual maturity, showed discrete reductions in the size and weight of the ectopic testes when compared with the scrotal testes. Immaturity of germinal line, tubular size, and intertubular spaces were more pronounced in the ectopic tissue. Both glands produced 4-androstenedione as a primary metabolic product of pregnenolone. Large prepuberal animals, puberal at the time of operation, showed tubular size, spermatic line, and interstitial tissue completely developed in the scrotal gland. Testosterone production was quite similar to that produced in postpuberal testes. The ectopic organ showed only Sertolic cells, some vacuolated, and a few spermatogonia in the tubules. The spaces contained Leydig cells. A significant accumulation of 4-adrenostenedione and a lower testosterone production, compared with that found in the scrotal gland, were observed. The histologic immaturity and the hormonal biosynthesis of the puberal cryptorchid testis parallel findings in scrotal glands from sexually immature guinea pigs.", "contents": "Androgen biosynthesis in experimental cryptorchidism. This study was conducted to investigate the effects of unilateral cryptorchidism on androgen production and testicular maturation. Experimental cryptorchidism was produced in small and large prepuberal guinea pigs by forcing the testis to remain in the abdomen for a period of 30 days. Small prepuberal animals, which did not reach sexual maturity, showed discrete reductions in the size and weight of the ectopic testes when compared with the scrotal testes. Immaturity of germinal line, tubular size, and intertubular spaces were more pronounced in the ectopic tissue. Both glands produced 4-androstenedione as a primary metabolic product of pregnenolone. Large prepuberal animals, puberal at the time of operation, showed tubular size, spermatic line, and interstitial tissue completely developed in the scrotal gland. Testosterone production was quite similar to that produced in postpuberal testes. The ectopic organ showed only Sertolic cells, some vacuolated, and a few spermatogonia in the tubules. The spaces contained Leydig cells. A significant accumulation of 4-adrenostenedione and a lower testosterone production, compared with that found in the scrotal gland, were observed. The histologic immaturity and the hormonal biosynthesis of the puberal cryptorchid testis parallel findings in scrotal glands from sexually immature guinea pigs."}
{"id": "PMID:238872", "title": "Activated paper as an immunoabsorbent.", "content": "Some workers when using cyanogen bromide activated paper as a solid immunoabsorbent have reported variable success in radio immuno assays. A quantitative investigation has been made of some of the factors which effect the activation of various papers with CNBr, and also of the subsequent coupling reaction with the sensitizing antigen. Different papers have been found to react in different ways, and some papers take up so little antigen that they are unsuitable for use for this purpose.", "contents": "Activated paper as an immunoabsorbent. Some workers when using cyanogen bromide activated paper as a solid immunoabsorbent have reported variable success in radio immuno assays. A quantitative investigation has been made of some of the factors which effect the activation of various papers with CNBr, and also of the subsequent coupling reaction with the sensitizing antigen. Different papers have been found to react in different ways, and some papers take up so little antigen that they are unsuitable for use for this purpose."}
{"id": "PMID:238873", "title": "Standardization of Dermatophagoides pteronyssinus extracts and tyrosine adsorbates.", "content": "Human skin test, inhibition of RAST and the radioimmunosorbent technique of Ceska have been shown to be useful assays for the standardization of D. pteronyssinus aqueous extracts. The development of these assay systems for the standardization of D. pteronyssinus tyrosine adsorbed formulations is described. Tyrosine solubilisation procedures are detailed together with the influence of these procedures on the three assays. Good correlation has been shown between the human skin test and the radioimmunosorbent technique. The inhibition of RAST appears to be more sensitive than the other techniques to mild conformational changes in the allergen, induced in this work by acid pH. This may limit its value for the standardization of D. pteronyssinus tyrosine adsorbates but it may prove useful in monitoring manufacturing processes.", "contents": "Standardization of Dermatophagoides pteronyssinus extracts and tyrosine adsorbates. Human skin test, inhibition of RAST and the radioimmunosorbent technique of Ceska have been shown to be useful assays for the standardization of D. pteronyssinus aqueous extracts. The development of these assay systems for the standardization of D. pteronyssinus tyrosine adsorbed formulations is described. Tyrosine solubilisation procedures are detailed together with the influence of these procedures on the three assays. Good correlation has been shown between the human skin test and the radioimmunosorbent technique. The inhibition of RAST appears to be more sensitive than the other techniques to mild conformational changes in the allergen, induced in this work by acid pH. This may limit its value for the standardization of D. pteronyssinus tyrosine adsorbates but it may prove useful in monitoring manufacturing processes."}
{"id": "PMID:238874", "title": "The multi-facets of tuberculin standardization.", "content": "Some parameters affecting the standardization of a tuberculin preparation have been evaluated and it has been shown that: 1) The loss of tuberculoprotein on the surfaces of containers is in the order of 0.15 mug/cm2 and the 0.18 mug/cm-2 for glass and plastic surfaces respectively, and that this loss can be prevented by the addition of a nonionic anti-adsorption agent such as Tween 80. 2) For non-stabilized tuberculin PPD solutions the losses of PPD due to adsorption increased linearly with the Surface to Volume ration. 3) Exposure to light had a deleterious effect on tuberculin PPD decreasing its biological potency and altering its appearance. This effect increased with the dilution of the tuberculoprotein solution, and can be prevented by storing the tuberculin in amber containers. 4) The potency of tuberculoprotein was dependent on its molecular weight, and the % distribution of tuberculoprotein molecules of different molecular weight varied from batch to batch. This variation can be eliminated by preparing a large batch of tuberculin in a dried form sufficient to fill the demand for many years to come. 5) The route of injection and the species or strains of mycobacteria used for sensitization of guinea pigs affected the relative potency of a tuberculin preparation. 6) The size of a tuberculin skin reaction increased as the volume of tuberculin injected intracutaneously into sensitized guinea pigs was increased although the number of tuberculin units administered was the same. 7) The sizes of skin reactions to certain doses of tuberculin was affected by other doses of tuberculin being injected simultaneously at other sites. 8) Sex and age of guinea pigs affected the size of the tuberculin skin reaction. 9) The genetic make-up of the test animals affected the relative potency of a given tuberculin preparation. 10) Racial differences among various populations might account for different levels of tuberculin reactivity to a given tuberculin preparation. It is hoped that this work has made us aware of the many problems which can be encountered in standardizing tuberculin and it is also to be hoped that the solutions we have offered to some of these problems can be useful to those attempting to standardize allergens other than tuberculin.", "contents": "The multi-facets of tuberculin standardization. Some parameters affecting the standardization of a tuberculin preparation have been evaluated and it has been shown that: 1) The loss of tuberculoprotein on the surfaces of containers is in the order of 0.15 mug/cm2 and the 0.18 mug/cm-2 for glass and plastic surfaces respectively, and that this loss can be prevented by the addition of a nonionic anti-adsorption agent such as Tween 80. 2) For non-stabilized tuberculin PPD solutions the losses of PPD due to adsorption increased linearly with the Surface to Volume ration. 3) Exposure to light had a deleterious effect on tuberculin PPD decreasing its biological potency and altering its appearance. This effect increased with the dilution of the tuberculoprotein solution, and can be prevented by storing the tuberculin in amber containers. 4) The potency of tuberculoprotein was dependent on its molecular weight, and the % distribution of tuberculoprotein molecules of different molecular weight varied from batch to batch. This variation can be eliminated by preparing a large batch of tuberculin in a dried form sufficient to fill the demand for many years to come. 5) The route of injection and the species or strains of mycobacteria used for sensitization of guinea pigs affected the relative potency of a tuberculin preparation. 6) The size of a tuberculin skin reaction increased as the volume of tuberculin injected intracutaneously into sensitized guinea pigs was increased although the number of tuberculin units administered was the same. 7) The sizes of skin reactions to certain doses of tuberculin was affected by other doses of tuberculin being injected simultaneously at other sites. 8) Sex and age of guinea pigs affected the size of the tuberculin skin reaction. 9) The genetic make-up of the test animals affected the relative potency of a given tuberculin preparation. 10) Racial differences among various populations might account for different levels of tuberculin reactivity to a given tuberculin preparation. It is hoped that this work has made us aware of the many problems which can be encountered in standardizing tuberculin and it is also to be hoped that the solutions we have offered to some of these problems can be useful to those attempting to standardize allergens other than tuberculin."}
{"id": "PMID:238890", "title": "[An analysis of the rise of health care costs in institutions in Canada and Quebec].", "content": "The author compares increases in institutional care costs in Quebec with the rest of Canada revealing the following: The 14 per cent annual increase reported by federal health minister Marc Lalonde is well above the increase in the Canadian population of 4 per cent. The 12 per cent rise in costs of Quebec health services is far above the increase in the population of 15 per cent. Therefore, population is not a major factor in cost increase. The rate of cost increase in Quebec is below the national rate, 12 per cent against 14 per cent. Cost of institutional care in dollars per capita is appreciably lower in Quebec than in the rest of Canada. The average increase in health care costs in Canada between 1970 and 1973 is actually above the average deseasonized increase rate of the gross national product (GNP). The average cost increase of institutional care remained, however, below the increase of the GNP in Canada. The increase in the number of patients admitted is far above the increase in population, in both Quebec and the other provinces, the difference being more important in Quebec than in the rest of Canada. Utilization has partly been possible through decrease in the average length of stay in both Quebec and the other provinces. The decrease in average length of stay is higher in other Canadian provinces than it is in Quebec. However, it is lower in Quebec for a day. The occupancy rate has consistantly been rising in Quebec while it remained stable in other provinces. The number of patients admitted per 1,000 population has remained much lower in Quebec as compared to the rest of Canda. The difference tends, however, to decrease. The number of institutional care facilities remains higher in other Canadian provinces than in Quebec in proportion to the population The number of visits in emergency units per 1,000 population has doubled in Quebec, as compared to the rest of Canada with half that increase. It would be interesting to establish the trend in institutional care for outpatient departments other than emergency units; complete data about this not as yet availble.", "contents": "[An analysis of the rise of health care costs in institutions in Canada and Quebec]. The author compares increases in institutional care costs in Quebec with the rest of Canada revealing the following: The 14 per cent annual increase reported by federal health minister Marc Lalonde is well above the increase in the Canadian population of 4 per cent. The 12 per cent rise in costs of Quebec health services is far above the increase in the population of 15 per cent. Therefore, population is not a major factor in cost increase. The rate of cost increase in Quebec is below the national rate, 12 per cent against 14 per cent. Cost of institutional care in dollars per capita is appreciably lower in Quebec than in the rest of Canada. The average increase in health care costs in Canada between 1970 and 1973 is actually above the average deseasonized increase rate of the gross national product (GNP). The average cost increase of institutional care remained, however, below the increase of the GNP in Canada. The increase in the number of patients admitted is far above the increase in population, in both Quebec and the other provinces, the difference being more important in Quebec than in the rest of Canada. Utilization has partly been possible through decrease in the average length of stay in both Quebec and the other provinces. The decrease in average length of stay is higher in other Canadian provinces than it is in Quebec. However, it is lower in Quebec for a day. The occupancy rate has consistantly been rising in Quebec while it remained stable in other provinces. The number of patients admitted per 1,000 population has remained much lower in Quebec as compared to the rest of Canda. The difference tends, however, to decrease. The number of institutional care facilities remains higher in other Canadian provinces than in Quebec in proportion to the population The number of visits in emergency units per 1,000 population has doubled in Quebec, as compared to the rest of Canada with half that increase. It would be interesting to establish the trend in institutional care for outpatient departments other than emergency units; complete data about this not as yet availble."}
{"id": "PMID:238893", "title": "Course and prognosis of 86 episodes of diabetic coma. A five year experience with a uniform schedule of treatment.", "content": "The admission data and the course of 58 episodes of severe diabetic ketoacidotic coma and of 28 episodes of non-ketotic coma are compared. The non-ketotic patients were older; initial blood glucose, osmolarity, blood urea and serum sodium concentration were higher than in the ketotic patients. Treatment in the first 24 hrs consisted of similar amounts of insulin in both coma forms, the presence of acidaemia did not increase the insulin needs. Acidaemia was corrected only when pH was below 7.20. The disadvantages of alkali therapy are emphasized. A comparison of the age groups of survivors and those patients who died within 72 hrs showed an increase in mortality with age. However, the mortality rates from ketotic and non-ketotic coma were similar in the age groups above 50 years. On admission, blood glucose, osmolarity and blood urea were higher in the fatal cases. Blood urea was the most important indicator of a fatal outcome. The response of blood glucose to insulin was impaired in the subsequently fatal cases. Insulin was given in \"moderate\" doses by constant infusion. The use of \"small\" doses is discussed. Early mortality was 14% in the ketotic and 29% in the non-ketotic cases. The most frequent causes of death were circulatory failure of undetermined origin, infections and thromboembolic complications.", "contents": "Course and prognosis of 86 episodes of diabetic coma. A five year experience with a uniform schedule of treatment. The admission data and the course of 58 episodes of severe diabetic ketoacidotic coma and of 28 episodes of non-ketotic coma are compared. The non-ketotic patients were older; initial blood glucose, osmolarity, blood urea and serum sodium concentration were higher than in the ketotic patients. Treatment in the first 24 hrs consisted of similar amounts of insulin in both coma forms, the presence of acidaemia did not increase the insulin needs. Acidaemia was corrected only when pH was below 7.20. The disadvantages of alkali therapy are emphasized. A comparison of the age groups of survivors and those patients who died within 72 hrs showed an increase in mortality with age. However, the mortality rates from ketotic and non-ketotic coma were similar in the age groups above 50 years. On admission, blood glucose, osmolarity and blood urea were higher in the fatal cases. Blood urea was the most important indicator of a fatal outcome. The response of blood glucose to insulin was impaired in the subsequently fatal cases. Insulin was given in \"moderate\" doses by constant infusion. The use of \"small\" doses is discussed. Early mortality was 14% in the ketotic and 29% in the non-ketotic cases. The most frequent causes of death were circulatory failure of undetermined origin, infections and thromboembolic complications."}
{"id": "PMID:238894", "title": "Properties of aryl hydrocarbon (benzo[a]pyrene) hydroxylase in the liver from C3H/He and DBA/2 strains of mice.", "content": "Aryl hydrocarbon hydroxylase activity in liver from the C3H/He strain of mice is apparently increased by the administration of 3-methylcholanthrene, but the enzyme activity from the DBA/2 strain of mice is not. The enzyme activity from female mice is higher than that from male mice, even 72 hr after a single application of 3-methylcholanthrene into the mice. The control enzyme in the liver from both strains of mice has a pH optimum at 7.9 and the induced enzyme from C3H/He mice, at 8.2. There are approximately the same levels of the apparent Km for benzo[a]pyrene, NADPH, or NADH in the liver enzyme from both strains of mice even after treatment with 3-methylcholanthrene. The induced enzyme is inhibited by 7,8- or 5,6-benzoflavone non-competitively, and nicotinamide inhibits both the constitutive and induced enzyme uncompetiviely. Cyclohexene oxide and 1,1,1-trichloropropane oxide, known to be inhbitors of epoxide hydrase, inhibit the activity of the constitutive enzyme, but enhance the induced enzyme in the liver. The difference in the properties between the constitutive and induced enzymes from mouse liver is discussed briefly.", "contents": "Properties of aryl hydrocarbon (benzo[a]pyrene) hydroxylase in the liver from C3H/He and DBA/2 strains of mice. Aryl hydrocarbon hydroxylase activity in liver from the C3H/He strain of mice is apparently increased by the administration of 3-methylcholanthrene, but the enzyme activity from the DBA/2 strain of mice is not. The enzyme activity from female mice is higher than that from male mice, even 72 hr after a single application of 3-methylcholanthrene into the mice. The control enzyme in the liver from both strains of mice has a pH optimum at 7.9 and the induced enzyme from C3H/He mice, at 8.2. There are approximately the same levels of the apparent Km for benzo[a]pyrene, NADPH, or NADH in the liver enzyme from both strains of mice even after treatment with 3-methylcholanthrene. The induced enzyme is inhibited by 7,8- or 5,6-benzoflavone non-competitively, and nicotinamide inhibits both the constitutive and induced enzyme uncompetiviely. Cyclohexene oxide and 1,1,1-trichloropropane oxide, known to be inhbitors of epoxide hydrase, inhibit the activity of the constitutive enzyme, but enhance the induced enzyme in the liver. The difference in the properties between the constitutive and induced enzymes from mouse liver is discussed briefly."}
{"id": "PMID:238895", "title": "Studies on the binding of amylopectin sulfate with gastric mucin.", "content": "Amylopectin sulfate, a sulfated polysaccharide that has an antipeptic property, was examined for its ability to bind gastric mucins. After chemically cross-linking the amylopectin sulfate into an insoluble gel, its binding with mucins isolated from antral and fundic mucosa of canine stomachs was studied with chromatography. A component present in both mucin fractions bound to the amylopectin sulfate gel below pH 4.5. This binding was reversible, and the complex dissociated above pH 5. Similar binding properties were found with soluble amylopectin sulfate. The component of the mucine which bound to amylopectin sulfate differed from the one which did not bind in its electrophoretic mobility and in its higher proportion of basic amino acids and a lower hexosamine, serine, and threonine content. This study suggests that amylopectin sulfate may bind to gastric mucins only under conditions of low pH.", "contents": "Studies on the binding of amylopectin sulfate with gastric mucin. Amylopectin sulfate, a sulfated polysaccharide that has an antipeptic property, was examined for its ability to bind gastric mucins. After chemically cross-linking the amylopectin sulfate into an insoluble gel, its binding with mucins isolated from antral and fundic mucosa of canine stomachs was studied with chromatography. A component present in both mucin fractions bound to the amylopectin sulfate gel below pH 4.5. This binding was reversible, and the complex dissociated above pH 5. Similar binding properties were found with soluble amylopectin sulfate. The component of the mucine which bound to amylopectin sulfate differed from the one which did not bind in its electrophoretic mobility and in its higher proportion of basic amino acids and a lower hexosamine, serine, and threonine content. This study suggests that amylopectin sulfate may bind to gastric mucins only under conditions of low pH."}
{"id": "PMID:238896", "title": "Unique enzymes of purified microsomes from pig fundic mucosa. K+-stimulated adenosine triphosphatase and K+-stimulated pNPPase.", "content": "Microsomal fractions from homogenates of pig gastric fundic mucosa showed high levels of K+-stimulated adenosine triphosphatase (ATPase) and K+-stimulated phosphatase. Similar preparations from antral mucosa showed virtually no such activity. Because of mitochondrial contamination the fundic microsomes were further separated by sucrose density gradient centrifugation. A low density band of membranes (peak 1.12 to 1.13 g per ml) possessed all of the K+-stimulated enzyme activities. Morphological features and the abundant glycoproteins of the low density microsomes suggested they might be derived from the tubulovesicles of oxyntic cells. Mitochondrial and ribosomal markers were associated with membranes with much higher densities (greater than 1.22). The K+-stimulated ATPase has a pH optimum of 7.5 and required Mg++, but neither Na+ nor ouabain had any appreciable effect on the activity. Stimulation of basal ATPase by K+ ranged from 1.5 to 3.0-fold with an apparent Ka for activation between 0.2 to 0.4 mM K+. Addition of various K+ ionophoretic substances (e.g., gramicidin) produced further stimulation of K+-ATPase up to 6 times the basal rate. The mean activities for seven separate preparations of purified low density pig fundic microsomes were as follows (micromoles of ATP hydrolyzed per mg protein per hr +/- SEM); basal ATPase, 15.8 +/- 2.8; plus 10 mM K+, 29.3 +/- 4.5; plus 10 mM K+ and 10(-5) M gramicidin, 45.2 +/- 5.2. Neither the basal ATPase nor the K+-stimulated rates were altered by HCO3- or Cl-. The occurrence of these active and unique enzyme activities in the oxyntic region of gastric mucosa suggest some relation with secretory activity. Possible functional roles are discussed.", "contents": "Unique enzymes of purified microsomes from pig fundic mucosa. K+-stimulated adenosine triphosphatase and K+-stimulated pNPPase. Microsomal fractions from homogenates of pig gastric fundic mucosa showed high levels of K+-stimulated adenosine triphosphatase (ATPase) and K+-stimulated phosphatase. Similar preparations from antral mucosa showed virtually no such activity. Because of mitochondrial contamination the fundic microsomes were further separated by sucrose density gradient centrifugation. A low density band of membranes (peak 1.12 to 1.13 g per ml) possessed all of the K+-stimulated enzyme activities. Morphological features and the abundant glycoproteins of the low density microsomes suggested they might be derived from the tubulovesicles of oxyntic cells. Mitochondrial and ribosomal markers were associated with membranes with much higher densities (greater than 1.22). The K+-stimulated ATPase has a pH optimum of 7.5 and required Mg++, but neither Na+ nor ouabain had any appreciable effect on the activity. Stimulation of basal ATPase by K+ ranged from 1.5 to 3.0-fold with an apparent Ka for activation between 0.2 to 0.4 mM K+. Addition of various K+ ionophoretic substances (e.g., gramicidin) produced further stimulation of K+-ATPase up to 6 times the basal rate. The mean activities for seven separate preparations of purified low density pig fundic microsomes were as follows (micromoles of ATP hydrolyzed per mg protein per hr +/- SEM); basal ATPase, 15.8 +/- 2.8; plus 10 mM K+, 29.3 +/- 4.5; plus 10 mM K+ and 10(-5) M gramicidin, 45.2 +/- 5.2. Neither the basal ATPase nor the K+-stimulated rates were altered by HCO3- or Cl-. The occurrence of these active and unique enzyme activities in the oxyntic region of gastric mucosa suggest some relation with secretory activity. Possible functional roles are discussed."}
{"id": "PMID:238897", "title": "Correlation between regional enterocolitis and cutaneous polyarteritis nodosa. Two case reports and review of the literature.", "content": "Dermatological manifestations of chronic infammatory bowel disease are numerous. We report herein 2 cases that demonstrated the uncommon association of cutaneous polyarteritis nodosa with regional enterocolitis. The clinical and histopathological features of this skin disease are important. Particular emphasis is placed on its relative benignity, in contrast to the serious prognosis associated with systemic polyarteritis nodosa.", "contents": "Correlation between regional enterocolitis and cutaneous polyarteritis nodosa. Two case reports and review of the literature. Dermatological manifestations of chronic infammatory bowel disease are numerous. We report herein 2 cases that demonstrated the uncommon association of cutaneous polyarteritis nodosa with regional enterocolitis. The clinical and histopathological features of this skin disease are important. Particular emphasis is placed on its relative benignity, in contrast to the serious prognosis associated with systemic polyarteritis nodosa."}
{"id": "PMID:238898", "title": "Effect of aspirin on ionic movement and acid hydrolase activity of explants of canine antral and duodenal mucosae.", "content": "Lucite chambers, applied to antral and proximal duodenal mucosae with blood supply intact, were used to compare ionic flux and the total, labilized activity of several acid hydrolases including cathepsin D, alpha and beta-galactosidase, beta-N-acetyglucosaminidase, arylsulfatase, and acid phosphatase. Insorption of H+ ion by the antrum is increased by the application of aspirin-acid-salt solution, which also stimulates acid hydrolase activity; acute erosions develop very rapidly. On the other hand, H+ ion is much more rapidly removed from chambers applied to the duodenal mucosa, isolated by the chamber from bile and pancreatic secretions. The same aspirin-acid-salt solution reduces net H+ ion loss from the duodenal chamber, depresses levels of the acid hydrolases, and no ulcers develop.", "contents": "Effect of aspirin on ionic movement and acid hydrolase activity of explants of canine antral and duodenal mucosae. Lucite chambers, applied to antral and proximal duodenal mucosae with blood supply intact, were used to compare ionic flux and the total, labilized activity of several acid hydrolases including cathepsin D, alpha and beta-galactosidase, beta-N-acetyglucosaminidase, arylsulfatase, and acid phosphatase. Insorption of H+ ion by the antrum is increased by the application of aspirin-acid-salt solution, which also stimulates acid hydrolase activity; acute erosions develop very rapidly. On the other hand, H+ ion is much more rapidly removed from chambers applied to the duodenal mucosa, isolated by the chamber from bile and pancreatic secretions. The same aspirin-acid-salt solution reduces net H+ ion loss from the duodenal chamber, depresses levels of the acid hydrolases, and no ulcers develop."}
{"id": "PMID:238899", "title": "Adenylate and guanylate cyclase activities and cellular differentiation in rat small intestine.", "content": "Adenylate and guanylate cyclase activities were measured in rat small intestinal villus and crypt cells to determine possible correlations with cellular differentiation. Isolated intestinal cells were prepared by a method which effectively separates differentiated villus cells from undifferentiated crypt cells (J Biol Chem 248:2542, 1973). Crypt cells were found to have a significantly lower guanylate cyclase activity than villus cells. Adenylate cyclase activity was higher in crypt cells than villus cells, although the difference was less striking than the reverse gradient observed for guanylate cyclase. There was no gradient of activity for cyclic guanosine 3':5'-monophosphate phosphodiesterase. However, cyclic adenosine 3':5'-monophosphate phosphodiesterase activity was lower in villus cells. No villus to crypt gradient of cyclic adenosine 3':5'-monophosphate concentration was detected in mucosa frozen rapidly in liquid nitrogen. The properties and subcellular localization of the cyclases were also evaluated, and of particular interest was the localization of guanylate cyclase to the microvillus membrane and the confirmation of adenylate cyclase activity in the lateral-basal membrane. The villus to crypt gradient of guanylate cyclase suggests that this enzyme has a specialized role in the differentiated villus cell. The contrasting subcellular localization of the cyclases suggests that the cyclases may be interrelated, possibly reflecting the epithelial cell polarity for absorption and secretion.", "contents": "Adenylate and guanylate cyclase activities and cellular differentiation in rat small intestine. Adenylate and guanylate cyclase activities were measured in rat small intestinal villus and crypt cells to determine possible correlations with cellular differentiation. Isolated intestinal cells were prepared by a method which effectively separates differentiated villus cells from undifferentiated crypt cells (J Biol Chem 248:2542, 1973). Crypt cells were found to have a significantly lower guanylate cyclase activity than villus cells. Adenylate cyclase activity was higher in crypt cells than villus cells, although the difference was less striking than the reverse gradient observed for guanylate cyclase. There was no gradient of activity for cyclic guanosine 3':5'-monophosphate phosphodiesterase. However, cyclic adenosine 3':5'-monophosphate phosphodiesterase activity was lower in villus cells. No villus to crypt gradient of cyclic adenosine 3':5'-monophosphate concentration was detected in mucosa frozen rapidly in liquid nitrogen. The properties and subcellular localization of the cyclases were also evaluated, and of particular interest was the localization of guanylate cyclase to the microvillus membrane and the confirmation of adenylate cyclase activity in the lateral-basal membrane. The villus to crypt gradient of guanylate cyclase suggests that this enzyme has a specialized role in the differentiated villus cell. The contrasting subcellular localization of the cyclases suggests that the cyclases may be interrelated, possibly reflecting the epithelial cell polarity for absorption and secretion."}
{"id": "PMID:238900", "title": "Intestinal villus and crypt cell responses to cholera toxin.", "content": "Adenylate cyclase activity was measured in rat small intestinal villus and crypt cells after in vivo and in vitro exposure to cholera toxin. The increase in intestinal adenylate cyclase induced by cholera toxin in vivo appeared to be largely confined to the villus cell with the largest increase observed for upper villus cells. Crypt cell adenylate cyclase was not responsive to cholera toxin. No response could be demonstrated for isolated villus or crypt cells incubated with cholera toxin in vitro. In vivo incubation with 125I-cholera toxin demonstrated binding to only villus cells. These results suggest that the major effect of cholera toxin was on villus cells rather than crypt cells and this was due to the greater accessibility or binding capacity of the villus cell to luminal cholera toxin.", "contents": "Intestinal villus and crypt cell responses to cholera toxin. Adenylate cyclase activity was measured in rat small intestinal villus and crypt cells after in vivo and in vitro exposure to cholera toxin. The increase in intestinal adenylate cyclase induced by cholera toxin in vivo appeared to be largely confined to the villus cell with the largest increase observed for upper villus cells. Crypt cell adenylate cyclase was not responsive to cholera toxin. No response could be demonstrated for isolated villus or crypt cells incubated with cholera toxin in vitro. In vivo incubation with 125I-cholera toxin demonstrated binding to only villus cells. These results suggest that the major effect of cholera toxin was on villus cells rather than crypt cells and this was due to the greater accessibility or binding capacity of the villus cell to luminal cholera toxin."}
{"id": "PMID:238901", "title": "[The clinical importance of abnormal heart rate tracings during labour (author's transl)].", "content": "A continuous fetal heart rate tracing of the first and second stage of labour was available for 221 labours and deliveries with varying histories of the present pregnancy. The importance of the abnormalities of the fetal heart rate in these tracings was interpreted in comparison to the development of fetal acidosis. There were no cases of fetal acidosis when changes of the basal frequency occured as an isolated phenomenon independant of the oscillation type. Variable decelerations without silent oscillation of loss of oscillation at the low of the deceleration led to a slight increase of fetal acidosis only after 10 decelerations. Late or combined decelerations were associated with fetal acidosis in 25% of the cases. The incidence of acidosis increase with the increase in the number of decelerations. According to our results the loss of oscillation at the low of the deceleration is of very great importance. Without loss of oscillation at the low of deceleration only 7.2% of the pH values were below normal whereas after 1 to 5 such losses of ascillation already 23.5% of the pH values were below normal. Following more than 10 decelerations with loss of oscillation 75% of the fetuses showed an acidosis. The first abnormal pH values were detectable not earlier than 20 minutes after the first sign of variable, late or combined decelerations in the cardiotocogram. Decelerations in combination with silent oscillation of the basal frequently or loss of fluctuation at the low of the deceleration were associated with fetal acidosis in 50% of the cases. Indications for fetal skalp blood sampling or termination of the labour were proposed in the light of our results.", "contents": "[The clinical importance of abnormal heart rate tracings during labour (author's transl)]. A continuous fetal heart rate tracing of the first and second stage of labour was available for 221 labours and deliveries with varying histories of the present pregnancy. The importance of the abnormalities of the fetal heart rate in these tracings was interpreted in comparison to the development of fetal acidosis. There were no cases of fetal acidosis when changes of the basal frequency occured as an isolated phenomenon independant of the oscillation type. Variable decelerations without silent oscillation of loss of oscillation at the low of the deceleration led to a slight increase of fetal acidosis only after 10 decelerations. Late or combined decelerations were associated with fetal acidosis in 25% of the cases. The incidence of acidosis increase with the increase in the number of decelerations. According to our results the loss of oscillation at the low of the deceleration is of very great importance. Without loss of oscillation at the low of deceleration only 7.2% of the pH values were below normal whereas after 1 to 5 such losses of ascillation already 23.5% of the pH values were below normal. Following more than 10 decelerations with loss of oscillation 75% of the fetuses showed an acidosis. The first abnormal pH values were detectable not earlier than 20 minutes after the first sign of variable, late or combined decelerations in the cardiotocogram. Decelerations in combination with silent oscillation of the basal frequently or loss of fluctuation at the low of the deceleration were associated with fetal acidosis in 50% of the cases. Indications for fetal skalp blood sampling or termination of the labour were proposed in the light of our results."}
{"id": "PMID:238904", "title": "Effect of gastric secretory inhibitors on the gastric mucosal barrier.", "content": "The effects of the synthetic prostaglandin 16, 16 dimethyl-E2 methyl ester (16-diMe-PGE2) and the histamine H2-receptor antagonist metiamide on the gastric mucosal barrier have been studied using the Heidenhain pouch dog model. The 16-diMe-PGE2 caused significant change in the ionic permeability of the mucosa when instilled into the pouch in a concentration of 300 mug/20 ml. Intravenous administration of 16-diMe-PGE2 did not alter the barrier nor did it alter the response of the mucosa to sodium taurocholate. Metiamide given into the pouch did not affect the mucosa barrier and the response to taurocholate was not affected when metiamide was given locally or intravenously.", "contents": "Effect of gastric secretory inhibitors on the gastric mucosal barrier. The effects of the synthetic prostaglandin 16, 16 dimethyl-E2 methyl ester (16-diMe-PGE2) and the histamine H2-receptor antagonist metiamide on the gastric mucosal barrier have been studied using the Heidenhain pouch dog model. The 16-diMe-PGE2 caused significant change in the ionic permeability of the mucosa when instilled into the pouch in a concentration of 300 mug/20 ml. Intravenous administration of 16-diMe-PGE2 did not alter the barrier nor did it alter the response of the mucosa to sodium taurocholate. Metiamide given into the pouch did not affect the mucosa barrier and the response to taurocholate was not affected when metiamide was given locally or intravenously."}
{"id": "PMID:238905", "title": "Problems connected with plasma renin activity measurements by angiotensin I radioimmunoassay.", "content": "The main application of the radioimmunoassay for angiotensin I is the measurement of plasma renin activity (PRA). Methods published for the measurement of PRA differ in many details and make the comparison of results difficult. This paper deals with some of the problems. 1. The radioactive labelling of angiotensin I using chloramine-T requires the purification of the labelled peptide. A method applying both anion exchange chromatography and gel filtration is described. It resulted in tracer angiotensins of very reproducible characteristics. 2. For the measurement of PRA, the pH of the plasma has to be adjusted prior to the incubation. The adjustment to the physiologic pH of 7.4 is recommended. 0.1 volume of a concentrated buffer controlled the pH during a three hours incubation without diluting the plasma too much. 3. At pH 7.4, EDTA, dimercaprol, and 8-hydroxyquinoline were found to inhibit converting enzyme and angiotensinases better than EDTA and DFP and should therefore be used as inhibiting agents. 4. Nonspecific cross reaction of antisera are the cause of the blank values when angiotensin I is measured in unextracted plasma. The problem of subtraction of a blank may be minimized by the selection of an antiserum of high specificity which shows no or only little nonspecific cross reaction. Lor or unmeasurable blank values will result.", "contents": "Problems connected with plasma renin activity measurements by angiotensin I radioimmunoassay. The main application of the radioimmunoassay for angiotensin I is the measurement of plasma renin activity (PRA). Methods published for the measurement of PRA differ in many details and make the comparison of results difficult. This paper deals with some of the problems. 1. The radioactive labelling of angiotensin I using chloramine-T requires the purification of the labelled peptide. A method applying both anion exchange chromatography and gel filtration is described. It resulted in tracer angiotensins of very reproducible characteristics. 2. For the measurement of PRA, the pH of the plasma has to be adjusted prior to the incubation. The adjustment to the physiologic pH of 7.4 is recommended. 0.1 volume of a concentrated buffer controlled the pH during a three hours incubation without diluting the plasma too much. 3. At pH 7.4, EDTA, dimercaprol, and 8-hydroxyquinoline were found to inhibit converting enzyme and angiotensinases better than EDTA and DFP and should therefore be used as inhibiting agents. 4. Nonspecific cross reaction of antisera are the cause of the blank values when angiotensin I is measured in unextracted plasma. The problem of subtraction of a blank may be minimized by the selection of an antiserum of high specificity which shows no or only little nonspecific cross reaction. Lor or unmeasurable blank values will result."}
{"id": "PMID:238906", "title": "Purification and properties of phosphofructokinase (EC 2.7.1.11) of Saccharomyces carlsbergensis.", "content": "A procedure for the purification of phosphofructokinase from brewer's yeast (Saccharomyces carlsbergensis) is reported. Treatments with organic solvents and heat were avoided and chromatographic and filtration techniques in the presence of phenylmethane sulfonyl fluoride were mainly used. The purified enzyme is homogeneous in disc gel electrophoresis and according to sedimentation velocity and equilibrium measurements in the ultracentrifuge. The isoelectric point determined by focusing was 5.3. Absorption spectra, fluorescence spectra and circular dichroism spectrum are given. The molecular weight of the purified enzyme determined by gel filtration was 720 000, in agreement with that of the enzyme in the raw extract. This confirms the results of sedimentation velocity experiments which gave a value of SO20, W equals 19.4. Alkaline treatment leads to a dissociation of the native enzyme, yielding an inactive species with a molecular weight of 360 000. In 6M guanidine hydrochloride the enzyme dissociates into subunits with a mean molecular weight of 90 000 as obtained by ultracentrifugation analysis. This suggests a structure composed of 8 monomers. The specific activity of the enzyme was 116 U/mg under optimum conditions. The enzyme activity was proportional to the enzyme concentration in the range of 6 times 10- minus 12 M to 3 times 10- minus 7 M. The Michaelis constants and Hill coefficients for fructose 6-phosphate and AMP, the pH optima, and the stability properties of the enzyme are reported. Furthermore, the activation energy is given and it is shown that under saturating conditions, a straight Arrhenius plot obtains, whereas the plot is discontinuous at high ATP concentrations and at pH 7.6.", "contents": "Purification and properties of phosphofructokinase (EC 2.7.1.11) of Saccharomyces carlsbergensis. A procedure for the purification of phosphofructokinase from brewer's yeast (Saccharomyces carlsbergensis) is reported. Treatments with organic solvents and heat were avoided and chromatographic and filtration techniques in the presence of phenylmethane sulfonyl fluoride were mainly used. The purified enzyme is homogeneous in disc gel electrophoresis and according to sedimentation velocity and equilibrium measurements in the ultracentrifuge. The isoelectric point determined by focusing was 5.3. Absorption spectra, fluorescence spectra and circular dichroism spectrum are given. The molecular weight of the purified enzyme determined by gel filtration was 720 000, in agreement with that of the enzyme in the raw extract. This confirms the results of sedimentation velocity experiments which gave a value of SO20, W equals 19.4. Alkaline treatment leads to a dissociation of the native enzyme, yielding an inactive species with a molecular weight of 360 000. In 6M guanidine hydrochloride the enzyme dissociates into subunits with a mean molecular weight of 90 000 as obtained by ultracentrifugation analysis. This suggests a structure composed of 8 monomers. The specific activity of the enzyme was 116 U/mg under optimum conditions. The enzyme activity was proportional to the enzyme concentration in the range of 6 times 10- minus 12 M to 3 times 10- minus 7 M. The Michaelis constants and Hill coefficients for fructose 6-phosphate and AMP, the pH optima, and the stability properties of the enzyme are reported. Furthermore, the activation energy is given and it is shown that under saturating conditions, a straight Arrhenius plot obtains, whereas the plot is discontinuous at high ATP concentrations and at pH 7.6."}
{"id": "PMID:238911", "title": "Induction of T-cell differentiation in the Bursa of Fabricius by a soluble thymus factor.", "content": "Bursal lymphocytes from White Leghorn chickens of different ages were incubated with a soluble thymus factor (STF), and tested for t-cell characteristics. Immunofluorescence staining with anti-T-cell serum showed a marked increase inthe percentage of bursal T lymphocytes in cell preparations from young chickensincubated with STF.  In older chickens (17 weeks) no such effect was observed. Bursal cells treated with STF were also able to elicit splenomegaly showing thatnot only antigenic but also functional T-cell characteristics had been induced in apopulation of bursal cells.  The fate of these bursal T-cell precursors is discussed in the context of known migratory patterns.", "contents": "Induction of T-cell differentiation in the Bursa of Fabricius by a soluble thymus factor. Bursal lymphocytes from White Leghorn chickens of different ages were incubated with a soluble thymus factor (STF), and tested for t-cell characteristics. Immunofluorescence staining with anti-T-cell serum showed a marked increase inthe percentage of bursal T lymphocytes in cell preparations from young chickensincubated with STF.  In older chickens (17 weeks) no such effect was observed. Bursal cells treated with STF were also able to elicit splenomegaly showing thatnot only antigenic but also functional T-cell characteristics had been induced in apopulation of bursal cells.  The fate of these bursal T-cell precursors is discussed in the context of known migratory patterns."}
{"id": "PMID:238912", "title": "Beta blocking drugs as anti-arrhythmic agents.", "content": "Fifteen years after the introduction of beta adrenergic blocking drugs into clinical medicine, there is satisfactory evidence indicating that this class of drug has significant anti-arrhythmic activity. The chief indications for using these drugs are for the control of sinus tachycardia digitalis dysrhythmias and for the control of rapid ventricular rates atrial and ventricular dysrhythmias. The mode of action is by antagonizing the cardiac actions of catecholamines on cardiac automaticity and conduction.", "contents": "Beta blocking drugs as anti-arrhythmic agents. Fifteen years after the introduction of beta adrenergic blocking drugs into clinical medicine, there is satisfactory evidence indicating that this class of drug has significant anti-arrhythmic activity. The chief indications for using these drugs are for the control of sinus tachycardia digitalis dysrhythmias and for the control of rapid ventricular rates atrial and ventricular dysrhythmias. The mode of action is by antagonizing the cardiac actions of catecholamines on cardiac automaticity and conduction."}
{"id": "PMID:238914", "title": "Citric acid contents in the ejaculate, significance of its determination in andrological diagnostics.", "content": "Critic acid was determined in the ejaculate in 100 cases. No significant correlations between citric acid values and other parameters of the spermiogram were found. In accordance with literary data we found low citric acid values in prostatitis and hypogonadism.", "contents": "Citric acid contents in the ejaculate, significance of its determination in andrological diagnostics. Critic acid was determined in the ejaculate in 100 cases. No significant correlations between citric acid values and other parameters of the spermiogram were found. In accordance with literary data we found low citric acid values in prostatitis and hypogonadism."}
{"id": "PMID:238915", "title": "Photographic measurements of retinal blood oxygen saturation: falling saturation rabbit experiments.", "content": "A noninvasive photographic method of measuring retinal blood oxygen saturation and arteriovenous oxygen difference was developed and calibrated on rabbits. The experiments reported show that the accuracy of the measurements made using the method is better than 1.0 per cent. The method is applicable to vessels located anywhere in the fundus and represents a significant improvement over previous methods.", "contents": "Photographic measurements of retinal blood oxygen saturation: falling saturation rabbit experiments. A noninvasive photographic method of measuring retinal blood oxygen saturation and arteriovenous oxygen difference was developed and calibrated on rabbits. The experiments reported show that the accuracy of the measurements made using the method is better than 1.0 per cent. The method is applicable to vessels located anywhere in the fundus and represents a significant improvement over previous methods."}
{"id": "PMID:238910", "title": "Effect of pH on plating efficiency, serum reguirement, and incorporation of radioactive precursors into human cells.", "content": "The plating efficiencies of two cell lines (HeLa-AT and WI26 Va) and one cell strain (KL2) appeared to be optimal at pH 7.6 At the optimal pH, ,sing organic buffers, the serum concentration could be reduced by one-half without affecting the initial growth rate or the final population density of the human skin fibroblast strain, KL2. It is suggested that an optimal pH lowers the serum requirement of the cells. The incorporation of [3-H]thymidine, [3-H]uridine, [-3H]fucose and [-14C]amino acids into KL2 was maximal at the pH which normally permits optimal growth of this cell strain. Protein turnover, as measured by loss to the medium of amino acids from prelabeled cells, was pH-independent. Thymidine incorporation did not correlate with culture growth in the cell strain, MS2A.", "contents": "Effect of pH on plating efficiency, serum reguirement, and incorporation of radioactive precursors into human cells. The plating efficiencies of two cell lines (HeLa-AT and WI26 Va) and one cell strain (KL2) appeared to be optimal at pH 7.6 At the optimal pH, ,sing organic buffers, the serum concentration could be reduced by one-half without affecting the initial growth rate or the final population density of the human skin fibroblast strain, KL2. It is suggested that an optimal pH lowers the serum requirement of the cells. The incorporation of [3-H]thymidine, [3-H]uridine, [-3H]fucose and [-14C]amino acids into KL2 was maximal at the pH which normally permits optimal growth of this cell strain. Protein turnover, as measured by loss to the medium of amino acids from prelabeled cells, was pH-independent. Thymidine incorporation did not correlate with culture growth in the cell strain, MS2A."}
{"id": "PMID:238918", "title": "The antiglycolytic action on dental plaque of amine chlorides.", "content": "The influence on the glycolytic activity of dental plaque of different amine-hydrochloride compounds 300, 315 and 356 (oleylamine) respectively at concentrations equimolar to their corresponding amine fluorides 297, 242 and 335 at 250 ppm F-concentrations and of hexetidine and sodium laurylsulfate was tested in an in vivo/in vitro combination. Hexetidine and sodium laurylsulfate were assessed at concentrations equimolar to compound 315. After having refrained from oral hygiene for three days four test subjects rinsed for 3 minutes with 10 ml H2O. Plaque was collected from interdental areas immediately after the control water rinse and 6 and 60 minutes after rinsing for 3 minutes with 10 ml of test solution. The plaque then was exposed in vitro to 10% glucose solution, and pH-decreases due to glycolysis were recorded for 30 minutes. Rinsing with amine chlorides resulted in strong inhibition of glycolytic activity 6 minutes as well as 1 hour after rinsing. Hexetidine and sodium laurylsulfate did not depress the fermentation of glucose.", "contents": "The antiglycolytic action on dental plaque of amine chlorides. The influence on the glycolytic activity of dental plaque of different amine-hydrochloride compounds 300, 315 and 356 (oleylamine) respectively at concentrations equimolar to their corresponding amine fluorides 297, 242 and 335 at 250 ppm F-concentrations and of hexetidine and sodium laurylsulfate was tested in an in vivo/in vitro combination. Hexetidine and sodium laurylsulfate were assessed at concentrations equimolar to compound 315. After having refrained from oral hygiene for three days four test subjects rinsed for 3 minutes with 10 ml H2O. Plaque was collected from interdental areas immediately after the control water rinse and 6 and 60 minutes after rinsing for 3 minutes with 10 ml of test solution. The plaque then was exposed in vitro to 10% glucose solution, and pH-decreases due to glycolysis were recorded for 30 minutes. Rinsing with amine chlorides resulted in strong inhibition of glycolytic activity 6 minutes as well as 1 hour after rinsing. Hexetidine and sodium laurylsulfate did not depress the fermentation of glucose."}
{"id": "PMID:238919", "title": "Simultaneous pH and fluoride telemetry from the oral cavity.", "content": "A new telemetric system was used to determine, simultaneously, plaque pH and salivary fluoride when sucrose-containing fluoride tablets of 0.25 mg and 1.0 mg NaF were dissolved in the oral cavity. Dissolution of 1.0 mg fluoride tablets on the dorsum of the tongue produced transient interproximal plaque acidification not lower than pH 5.2 combined with an increased salivary F-level between 0.19 and 19 ppm for up to 1 hr at the entrance of the interproximal space. Interference of plaque glycolysis by F was evident when rinsings with 250 ppm F as NaF combined with 10% sucrose resulted in pH levels 1/2-1 unit higher than with 10 percent sucrose alone. The use of sucrose as a vehicle in fluoride tablets is discussed.", "contents": "Simultaneous pH and fluoride telemetry from the oral cavity. A new telemetric system was used to determine, simultaneously, plaque pH and salivary fluoride when sucrose-containing fluoride tablets of 0.25 mg and 1.0 mg NaF were dissolved in the oral cavity. Dissolution of 1.0 mg fluoride tablets on the dorsum of the tongue produced transient interproximal plaque acidification not lower than pH 5.2 combined with an increased salivary F-level between 0.19 and 19 ppm for up to 1 hr at the entrance of the interproximal space. Interference of plaque glycolysis by F was evident when rinsings with 250 ppm F as NaF combined with 10% sucrose resulted in pH levels 1/2-1 unit higher than with 10 percent sucrose alone. The use of sucrose as a vehicle in fluoride tablets is discussed."}
{"id": "PMID:238920", "title": "Relationships between mitochondrial content of muscle fibres and patterns of glyogendepletion postmortem.", "content": "Sternomandibularis muscles were removed from slaughtered adult cattle immediately after exsanguination. On the basis of the density of diformazan granules deposited by a reaction for NAD tetrazolium reductase, approximately equal numbers of muscle fibres with high and low mitochondrial content were identified in serial frozen sections. In samples taken immediately after exanguination both types of muscle fibres exhibited glycogen phosphorylase activity and were stained equally by the periodic acid-Schiff (PAS) reaction for glycogen. In unstimulated muscle samples 1 hr postmortem, no loss of PAS staining was detected. In electrically stimulated samples 1 hr postmortem, large numbers of muscle fibres with a low mitochondrial content but only some muscle fibres with a high mitochondrial content became PAS-negative. Stimulation-induced glycogen depletion was completely prevented by the interfaicular injection of magnesium sulphate solution. In unstimulated samples between 5 and 24 hr postmortem, some muscle fibres with a high mitochondrial content but only a few muscle fibres with a low mitochondrial content became PAS-negative.", "contents": "Relationships between mitochondrial content of muscle fibres and patterns of glyogendepletion postmortem. Sternomandibularis muscles were removed from slaughtered adult cattle immediately after exsanguination. On the basis of the density of diformazan granules deposited by a reaction for NAD tetrazolium reductase, approximately equal numbers of muscle fibres with high and low mitochondrial content were identified in serial frozen sections. In samples taken immediately after exanguination both types of muscle fibres exhibited glycogen phosphorylase activity and were stained equally by the periodic acid-Schiff (PAS) reaction for glycogen. In unstimulated muscle samples 1 hr postmortem, no loss of PAS staining was detected. In electrically stimulated samples 1 hr postmortem, large numbers of muscle fibres with a low mitochondrial content but only some muscle fibres with a high mitochondrial content became PAS-negative. Stimulation-induced glycogen depletion was completely prevented by the interfaicular injection of magnesium sulphate solution. In unstimulated samples between 5 and 24 hr postmortem, some muscle fibres with a high mitochondrial content but only a few muscle fibres with a low mitochondrial content became PAS-negative."}
{"id": "PMID:238921", "title": "Effect of glutaraldehyde and lead on the activity of hepatic glucose-6-phosphatase. A biochemical and cytochemical study.", "content": "The sensitivity of mouse liver glucose-6-phosphatase activity towards glutaraldehyde fixation has been analysed by biochemical and cytochemical means. The degree of enzymatic inhibition and various enzymatic properties have been studied. Several differences have been observed in the Km determination, the sensitivity to pH 5 and the activity related to pH between fixed and unfixed enzymes. The role of Pb++ ions in the cytochemical media has also been estimated. It is concluded that several enzymatic differences appear between fixed and unfixed enzymes and that the inhibition by Pb ions is dependent on the buffer and on the amount of substrate used.", "contents": "Effect of glutaraldehyde and lead on the activity of hepatic glucose-6-phosphatase. A biochemical and cytochemical study. The sensitivity of mouse liver glucose-6-phosphatase activity towards glutaraldehyde fixation has been analysed by biochemical and cytochemical means. The degree of enzymatic inhibition and various enzymatic properties have been studied. Several differences have been observed in the Km determination, the sensitivity to pH 5 and the activity related to pH between fixed and unfixed enzymes. The role of Pb++ ions in the cytochemical media has also been estimated. It is concluded that several enzymatic differences appear between fixed and unfixed enzymes and that the inhibition by Pb ions is dependent on the buffer and on the amount of substrate used."}
{"id": "PMID:238922", "title": "Semipermeable membranes for improving the histochemical demonstration of enzyme activities in tissue sections. V. Isocitrate: NADP+ oxidoreductase (decarboxylating) and malate: NADP+ oxidoreductase (decarboxylating).", "content": "Improved histochemical techniques for the demonstration of NADP+-specific isocitrate dehydrogenase and malate dehydrogenase in tissue sections are described. With these techniques a semipermeable membrane is interposed between the incubating solutions and the tissue sections preventing diffusion of enzymes into the medium during incubation. In the histochemical system the NADP+-dependent enzymes catalyze the electron transfer from threo-Ds-isocitrate or L-malate into NADP+. Phenazine methosulphate and menadione serve as intermediate electron acceptors between reduced coenzyme and nitro-BT. Sodium-azide and amytal are incorporated into the incubating-medium to block electron transfer to the cytochromes. For demonstrating enzyme activities in sections containing non-specific alkaline phosphatase, a phosphatase inhibitor is added into the incubation media. Problems involved in the histochemical demonstration of both enzymes are discussed.", "contents": "Semipermeable membranes for improving the histochemical demonstration of enzyme activities in tissue sections. V. Isocitrate: NADP+ oxidoreductase (decarboxylating) and malate: NADP+ oxidoreductase (decarboxylating). Improved histochemical techniques for the demonstration of NADP+-specific isocitrate dehydrogenase and malate dehydrogenase in tissue sections are described. With these techniques a semipermeable membrane is interposed between the incubating solutions and the tissue sections preventing diffusion of enzymes into the medium during incubation. In the histochemical system the NADP+-dependent enzymes catalyze the electron transfer from threo-Ds-isocitrate or L-malate into NADP+. Phenazine methosulphate and menadione serve as intermediate electron acceptors between reduced coenzyme and nitro-BT. Sodium-azide and amytal are incorporated into the incubating-medium to block electron transfer to the cytochromes. For demonstrating enzyme activities in sections containing non-specific alkaline phosphatase, a phosphatase inhibitor is added into the incubation media. Problems involved in the histochemical demonstration of both enzymes are discussed."}
{"id": "PMID:238923", "title": "Effect of storage on oxygen dissociation of canine blood.", "content": "Oxygen dissociation curve and adenosine triphosphate (ATP) and 2,3-diphosphoglycerate (DPG) contents in red blood cells (RBC) were determined in canine blood stored in acid citrate dextrose (ACD) and citrate phosphate dextrose (CPD) solutions. The oxygen-unloading ability decreased, as shown by the left shift of oxygen dissociation curve during storage, and the shift correlated with decreasing DPG but not decreasing ATP concentrations. After 2 weeks of storage in ACD solution, oxygen dissociation curves were shifted significantly to the left. For blood stored in CPD solution, 4 weeks was required before the shift was significant. It was concluded that canine blood collected and stored in CPD solution is more efficient than that stored in ACD solution in delivering oxygen to the tissues.", "contents": "Effect of storage on oxygen dissociation of canine blood. Oxygen dissociation curve and adenosine triphosphate (ATP) and 2,3-diphosphoglycerate (DPG) contents in red blood cells (RBC) were determined in canine blood stored in acid citrate dextrose (ACD) and citrate phosphate dextrose (CPD) solutions. The oxygen-unloading ability decreased, as shown by the left shift of oxygen dissociation curve during storage, and the shift correlated with decreasing DPG but not decreasing ATP concentrations. After 2 weeks of storage in ACD solution, oxygen dissociation curves were shifted significantly to the left. For blood stored in CPD solution, 4 weeks was required before the shift was significant. It was concluded that canine blood collected and stored in CPD solution is more efficient than that stored in ACD solution in delivering oxygen to the tissues."}
{"id": "PMID:238925", "title": "A new parenteral cephalosporin. SK&F 59962: in vitro and in vivo antibacterial activity and serum levels in experimental animals.", "content": "SK&F 59962, a new parenteral cephalosporin was found to have a high order of in vitro and in vivo antibacterial activity against a broad-spectrum of clinical isolates. When tested in vitro against gram-negative organisms, SK&F 59962 was consistently more active than cefazolin and far superior to cephalothin. This new antibiotic had activity equal to that of cephalothin against gram-positive bacteria. Enterobacter species were found to be susceptible to SK&F 59962. In mouse infection studies using bacterial pathogens, SK&F 59962 had protective activity of the order of that of cefazolin and superior to that of cephalothin. Following parenteral administration the serum profile of SK&F 59962 in the mouse, dog and squirrel monkey was similar to that of cephalothin. SK&F 59962 and cephalothin had lower peak serum concentrations and shorter biologic half-lives than those of cefazolin.", "contents": "A new parenteral cephalosporin. SK&F 59962: in vitro and in vivo antibacterial activity and serum levels in experimental animals. SK&F 59962, a new parenteral cephalosporin was found to have a high order of in vitro and in vivo antibacterial activity against a broad-spectrum of clinical isolates. When tested in vitro against gram-negative organisms, SK&F 59962 was consistently more active than cefazolin and far superior to cephalothin. This new antibiotic had activity equal to that of cephalothin against gram-positive bacteria. Enterobacter species were found to be susceptible to SK&F 59962. In mouse infection studies using bacterial pathogens, SK&F 59962 had protective activity of the order of that of cefazolin and superior to that of cephalothin. Following parenteral administration the serum profile of SK&F 59962 in the mouse, dog and squirrel monkey was similar to that of cephalothin. SK&F 59962 and cephalothin had lower peak serum concentrations and shorter biologic half-lives than those of cefazolin."}
{"id": "PMID:238926", "title": "Antimicrobial properties of mannopeptins.", "content": "Mannopeptins show in vitro antimicrobial activity against gram-positive and some gram-negative bacteria. The antimicrobial activity is unaffected by the addition of serum, and potentiated by alkaline pH or decrease in inoculum size. The antibiotics exert bectericidal effect at doses twice as high as the minimum inhibitory concentration. When the antibiotics were injected into mice through either intravenous, intraperitoneal, intramuscular or subcutaneous routes, the antimicrobial activity appeared within 15 minutes in the serum of mice and was slowly excreted in the urine. However, the antibiotics were poorly absorbed by the oral route. The antibiotics were capable of protecting mice from lethal infection produced by the intravenous injection of Staphylococcus aureus, Streptococcus pyogenes and the intraperitoneal injection of Shigella sp. and Escherichia coli, but ineffective against Salmonella typhosa.", "contents": "Antimicrobial properties of mannopeptins. Mannopeptins show in vitro antimicrobial activity against gram-positive and some gram-negative bacteria. The antimicrobial activity is unaffected by the addition of serum, and potentiated by alkaline pH or decrease in inoculum size. The antibiotics exert bectericidal effect at doses twice as high as the minimum inhibitory concentration. When the antibiotics were injected into mice through either intravenous, intraperitoneal, intramuscular or subcutaneous routes, the antimicrobial activity appeared within 15 minutes in the serum of mice and was slowly excreted in the urine. However, the antibiotics were poorly absorbed by the oral route. The antibiotics were capable of protecting mice from lethal infection produced by the intravenous injection of Staphylococcus aureus, Streptococcus pyogenes and the intraperitoneal injection of Shigella sp. and Escherichia coli, but ineffective against Salmonella typhosa."}
{"id": "PMID:238927", "title": "Negative arterial-mixed expired PC02 gradient during acute and chronic hypercapnia.", "content": "In resting conscious dogs physiological dead space was calculated using the Bohr equation and measurements of arterial and mixed expired carbon dioxide tension. Whenever dogs inhaled carbon dioxide mixtures (5-10%) that had normal or low oxygen concentrations, the calculated dead space became negative. This paradox was based on the fact that the mixed expired carbon dioxide tension in resting hypercapnic dogs. Under these circumstances carbon dioxide was produced from the lung as measured by gas analyses and blood analyses. By the lung as measured by gas analyses and blood analyses. By reasoning this implies that \"alveolar\" carbon dioxide tension was higher than pulmonary venous carbon dioxide tension. The negative carbon dioxide gradient persisted at 14 days of chronic hypercapnia and reverted to normal within 10 min of breathing air after chronic hypercapnia. These findings suggest that the exchange of carbon dioxide in the lung cannot be explained solely on the basis of passive diffusion.", "contents": "Negative arterial-mixed expired PC02 gradient during acute and chronic hypercapnia. In resting conscious dogs physiological dead space was calculated using the Bohr equation and measurements of arterial and mixed expired carbon dioxide tension. Whenever dogs inhaled carbon dioxide mixtures (5-10%) that had normal or low oxygen concentrations, the calculated dead space became negative. This paradox was based on the fact that the mixed expired carbon dioxide tension in resting hypercapnic dogs. Under these circumstances carbon dioxide was produced from the lung as measured by gas analyses and blood analyses. By the lung as measured by gas analyses and blood analyses. By reasoning this implies that \"alveolar\" carbon dioxide tension was higher than pulmonary venous carbon dioxide tension. The negative carbon dioxide gradient persisted at 14 days of chronic hypercapnia and reverted to normal within 10 min of breathing air after chronic hypercapnia. These findings suggest that the exchange of carbon dioxide in the lung cannot be explained solely on the basis of passive diffusion."}
{"id": "PMID:238928", "title": "Gastroesophageal dynamics during immersion in water to the neck.", "content": "This investigation was undertaken to study the effect of hydrostatic pressure on gastroesophageal dynamics during immersion in thermoneutral water to the neck. In 5 healthy male subjects (normal end-expiratory), gastric pressure (PG), esophageal pressure (PE), location and pressure of distal esophageal sphincter (des), location of respiratory inversion point (RIP), and gastroesophageal pH gradient were measured standing in air (A), standing in water to the neck (B), and standing in air with abdominal compression (C). The pressure was measured with a Honeywell esophageal catheter (model 31) with built-in pressure transducer. A Beckman stomach pH electrode (no. 39042) was positioned adjacent to the pressure transducer. PG increased from 4.6 +/- 0.6 (SE) mmHg in A to nearly 20 mmHg in B and C, while PE increased from -6.0 +/- 0.8 mmHg in A to -0.8 +/- 1.0 and -3.4 +/- 0.9 mmHg in B and C, respectively. However, PDES was always 11-15 mmHg higher than PG. The superior limit of DES was displaced cephalad by indicating a stretching of DES and a shortening of the esophagus. Qualitatively similar findings were obtained in C. In all experiments, the esophageal pH remained above 6, and no alteration in the amplitude of primary peristaltic waves was seen. It is concluded that a head-out immersion with increased gastroesophageal pressure gradient predisposes to gastric reflux in the absence of a competent DES mechanism.", "contents": "Gastroesophageal dynamics during immersion in water to the neck. This investigation was undertaken to study the effect of hydrostatic pressure on gastroesophageal dynamics during immersion in thermoneutral water to the neck. In 5 healthy male subjects (normal end-expiratory), gastric pressure (PG), esophageal pressure (PE), location and pressure of distal esophageal sphincter (des), location of respiratory inversion point (RIP), and gastroesophageal pH gradient were measured standing in air (A), standing in water to the neck (B), and standing in air with abdominal compression (C). The pressure was measured with a Honeywell esophageal catheter (model 31) with built-in pressure transducer. A Beckman stomach pH electrode (no. 39042) was positioned adjacent to the pressure transducer. PG increased from 4.6 +/- 0.6 (SE) mmHg in A to nearly 20 mmHg in B and C, while PE increased from -6.0 +/- 0.8 mmHg in A to -0.8 +/- 1.0 and -3.4 +/- 0.9 mmHg in B and C, respectively. However, PDES was always 11-15 mmHg higher than PG. The superior limit of DES was displaced cephalad by indicating a stretching of DES and a shortening of the esophagus. Qualitatively similar findings were obtained in C. In all experiments, the esophageal pH remained above 6, and no alteration in the amplitude of primary peristaltic waves was seen. It is concluded that a head-out immersion with increased gastroesophageal pressure gradient predisposes to gastric reflux in the absence of a competent DES mechanism."}
{"id": "PMID:238929", "title": "Inherited susceptibility of cattle to high-altitude pulmonary hypertension.", "content": "This study examines the hypothesis that susceptibility of cattle to high-altitude pulmonary hypertension and heart failure (high mountain disease) is genetically transmitted. Eight offspring of cattle recovered from high mountain disease were considered \"susceptible.\" Eleven offspring of healthy cattle residing at high altitude were considered \"resistant.\" At the resident altitude of 1,524 m, 10-day-old susceptible calves had higher pulmonary arterial pressures than did resistant calves (34 vs.21 mmHg), but at 90 days of age the pressures for the two groups were similar (26 vs. 24 mmHg). After 64 days of exposure to an altitude of 3,048 m, the susceptible calves (87 +/- 7 (SE) vs. 40 +/- 3 mmHg). By 124 days at 3,048 m, all susceptible but none of the resistant calves had developed heart failure. The results indicated that susceptibility to pulmonary hypertension at high altitude was inherited. Susceptible cattle may provide a useful model of human hypoxic pulmonary hypertension.", "contents": "Inherited susceptibility of cattle to high-altitude pulmonary hypertension. This study examines the hypothesis that susceptibility of cattle to high-altitude pulmonary hypertension and heart failure (high mountain disease) is genetically transmitted. Eight offspring of cattle recovered from high mountain disease were considered \"susceptible.\" Eleven offspring of healthy cattle residing at high altitude were considered \"resistant.\" At the resident altitude of 1,524 m, 10-day-old susceptible calves had higher pulmonary arterial pressures than did resistant calves (34 vs.21 mmHg), but at 90 days of age the pressures for the two groups were similar (26 vs. 24 mmHg). After 64 days of exposure to an altitude of 3,048 m, the susceptible calves (87 +/- 7 (SE) vs. 40 +/- 3 mmHg). By 124 days at 3,048 m, all susceptible but none of the resistant calves had developed heart failure. The results indicated that susceptibility to pulmonary hypertension at high altitude was inherited. Susceptible cattle may provide a useful model of human hypoxic pulmonary hypertension."}
{"id": "PMID:238930", "title": "Correlation of acute with chronic hypoxic pulmonary hypertension in cattle.", "content": "We investigated acute and chronic hypoxic pulmonary pressor responses in two groups of calves, one bred to be susceptible, the other resistant to high-altitude pulmonary hypertension. Twelve 5-mo-old susceptible calves residing at 1,524 m increased their mean pulmonary arterial pressure from 26 +/- 2 (SE) to 55 +/- 4 mmHg during 2 h at a simulated altitude of 4,572 m. In 10 resistant calves pressure increased from 22 +/- 1 to 37 +/- 2 mmHg. Five calves were selected from each group for further study. When 9 mo old, the 5 susceptible calves again showed a greater pressor response to acute hypoxia (27 +/- 1 to 55 +/- 4 mmHg) than did 5 resistant calves (23 +/- 1 to 41 +/- 3 mmHg). When 12 mo old, the 5 susceptible calves also developed a greater increase in pulmonary arterial pressure (21 +/- 2 to 9 +/- 4 mmHg) during 18 days at 4,572 m than did the 5 resistant calves (21 +/- 1 to 64 +/- 4 mmHg). Acute and chronic hypoxic pulmonary pressor responses were highly correlated (r = 0.91; P less than 0.001) indicating that they were probably produced through a common mechanism.", "contents": "Correlation of acute with chronic hypoxic pulmonary hypertension in cattle. We investigated acute and chronic hypoxic pulmonary pressor responses in two groups of calves, one bred to be susceptible, the other resistant to high-altitude pulmonary hypertension. Twelve 5-mo-old susceptible calves residing at 1,524 m increased their mean pulmonary arterial pressure from 26 +/- 2 (SE) to 55 +/- 4 mmHg during 2 h at a simulated altitude of 4,572 m. In 10 resistant calves pressure increased from 22 +/- 1 to 37 +/- 2 mmHg. Five calves were selected from each group for further study. When 9 mo old, the 5 susceptible calves again showed a greater pressor response to acute hypoxia (27 +/- 1 to 55 +/- 4 mmHg) than did 5 resistant calves (23 +/- 1 to 41 +/- 3 mmHg). When 12 mo old, the 5 susceptible calves also developed a greater increase in pulmonary arterial pressure (21 +/- 2 to 9 +/- 4 mmHg) during 18 days at 4,572 m than did the 5 resistant calves (21 +/- 1 to 64 +/- 4 mmHg). Acute and chronic hypoxic pulmonary pressor responses were highly correlated (r = 0.91; P less than 0.001) indicating that they were probably produced through a common mechanism."}
{"id": "PMID:238931", "title": "CSF bicarbonate regulation in respiratory acidosis and alkalosis.", "content": "CSF bicarbonate regulation was studied in respiratory acidosis and alkalosis of 4h duration in antsthetized dogs. PCO2, pH, HCO3, ammonia, and lactate in CSF and arterial and safittal sinus bloof were measured when equal volumes of saline or acetazolamide (8 mg) were injected into lateral cerebral ventricles. The brain CO2 dissociation curve was determined at the end of all experiments. CSF and arterial bicarbonate increased 11.8 and 5.9 meg/l, respectively, in acidosis. Acetazolamide limited the rise in CSF bicarbonate to 4.2 meg/l, and prevented the CSF bicarbonate increase associated with hyperammonemia. During alkalosis CSF bicarbonate fell 6.5 meg/l and CSF lactate increased almost 2 meg/l while arterial bicarbonate fell 5.7 meg/l and lactate remained unchanged. Thus plasma bicarbonate changes account for some of the CSF unchanged. Thus plasma bicarbonate changes account for some of the CSF bicarbonate alterations in respiratory acid-base-disturbances. In acidosis additional CSF bicarbonate is formed by the choroid plexus and glial cells on the inner and outer surfaces of the brain--a reaction catalyzed by the locally present carbonic anhydrase. In alkalosis the greater fall in CSF bicarbonate than blood is due to selective brain and CSF lactic acidosis.", "contents": "CSF bicarbonate regulation in respiratory acidosis and alkalosis. CSF bicarbonate regulation was studied in respiratory acidosis and alkalosis of 4h duration in antsthetized dogs. PCO2, pH, HCO3, ammonia, and lactate in CSF and arterial and safittal sinus bloof were measured when equal volumes of saline or acetazolamide (8 mg) were injected into lateral cerebral ventricles. The brain CO2 dissociation curve was determined at the end of all experiments. CSF and arterial bicarbonate increased 11.8 and 5.9 meg/l, respectively, in acidosis. Acetazolamide limited the rise in CSF bicarbonate to 4.2 meg/l, and prevented the CSF bicarbonate increase associated with hyperammonemia. During alkalosis CSF bicarbonate fell 6.5 meg/l and CSF lactate increased almost 2 meg/l while arterial bicarbonate fell 5.7 meg/l and lactate remained unchanged. Thus plasma bicarbonate changes account for some of the CSF unchanged. Thus plasma bicarbonate changes account for some of the CSF bicarbonate alterations in respiratory acid-base-disturbances. In acidosis additional CSF bicarbonate is formed by the choroid plexus and glial cells on the inner and outer surfaces of the brain--a reaction catalyzed by the locally present carbonic anhydrase. In alkalosis the greater fall in CSF bicarbonate than blood is due to selective brain and CSF lactic acidosis."}
{"id": "PMID:238932", "title": "Avian ventilatory responses to dynamic CO2 signals.", "content": "This study uses an awake unidirectionally ventilated avian preparation to examine the effects of dynamic CO2 signals on the respiratory drive. Results show that minute ventilation is affected by both 1) mean CO2 level and 2) amplitude of CO2 oscillations at the frequency of breathing. An increase in mean CO2 level increased minute ventilation. Comparisons of the effects of CO2 oscillations at the same mean CO2 level, however, showed minute ventilation to be less with the larger amplitudes of oscillations than with smaller ones. Graphs of minute ventilation (V)  versus mean CO2 for families of oscillation sizes (0.5%, 1% and 2%) showed that the ventilatory sensitivity (slop) was least for the 2% oscillations and greatest for the 0.5% oscillations. Therefore, a static model for the respiratory regulator is not adequate. However, the apneic level of CO2 (V = O intercept) was independent of the size of the CO2 oscillations.", "contents": "Avian ventilatory responses to dynamic CO2 signals. This study uses an awake unidirectionally ventilated avian preparation to examine the effects of dynamic CO2 signals on the respiratory drive. Results show that minute ventilation is affected by both 1) mean CO2 level and 2) amplitude of CO2 oscillations at the frequency of breathing. An increase in mean CO2 level increased minute ventilation. Comparisons of the effects of CO2 oscillations at the same mean CO2 level, however, showed minute ventilation to be less with the larger amplitudes of oscillations than with smaller ones. Graphs of minute ventilation (V)  versus mean CO2 for families of oscillation sizes (0.5%, 1% and 2%) showed that the ventilatory sensitivity (slop) was least for the 2% oscillations and greatest for the 0.5% oscillations. Therefore, a static model for the respiratory regulator is not adequate. However, the apneic level of CO2 (V = O intercept) was independent of the size of the CO2 oscillations."}
{"id": "PMID:238933", "title": "Gas-liquid chromatographic determination of diethylstilbestrol in molasses-based liquid feed supplements.", "content": "A gas-liquid chromatographic (GLC) method is described for the determination of diethylstilbestrol (DES) in molasses-based liquid feed supplements, using dienestrol diacetate as the internal standard. A sample equivalent to 110 mug DES was diluted, acidified with dilute sulfuric acid, extracted with chloroform, and subjected to basic sodium acetate cleanup. The bis-(trimethylsilyl) acetamide derivative was prepared and determined by GLC. Interfering peaks and/or low recoveries were found to be related to emulsions and the procedure incorporates centrifugation to minimize these.", "contents": "Gas-liquid chromatographic determination of diethylstilbestrol in molasses-based liquid feed supplements. A gas-liquid chromatographic (GLC) method is described for the determination of diethylstilbestrol (DES) in molasses-based liquid feed supplements, using dienestrol diacetate as the internal standard. A sample equivalent to 110 mug DES was diluted, acidified with dilute sulfuric acid, extracted with chloroform, and subjected to basic sodium acetate cleanup. The bis-(trimethylsilyl) acetamide derivative was prepared and determined by GLC. Interfering peaks and/or low recoveries were found to be related to emulsions and the procedure incorporates centrifugation to minimize these."}
{"id": "PMID:238934", "title": "Collaborative study of an on-column periodate reaction method for the determination of ephedrine sulfate in sirups.", "content": "Fifteen laboratories collaboratively studied a method for the quantitative ultraviolet determination of ephedrine sulfate in sirups. Ephedrine is separated from water-soluble impurities and strong acids by elution from a weakly basic Celite column. Further cleanup is accomplished by retention of the ephedrine on a weakly acidic column while the weak acids, weak bases, and organic-soluble neutral compounds are eluted. Ephedrine is eluted from the column after neutralization with NH3 and is converted to benzaldehyde via an on-column periodate reaction. The samples collaboratively studied consisted of 2 commericial ephedrine-containing sirups and 2 commercial non-ephedrine-containing sirups to which ephedrine was added. Recoveries for the spiked sirups averaged 100.7 and 100.3% for mixtures containing 2.5 and 5.0 mg ephedrine sulfate/ml, respectively. The means and standard deviations for the commercial preparations were 4.088 plus or minus 0.068 and 2.375 plus or minus 0.053 mg/ml. The method has been adopted as official first action and has been incorporated into the official method for phenylpropanolamine hydrochloride, 38.199-38.203.", "contents": "Collaborative study of an on-column periodate reaction method for the determination of ephedrine sulfate in sirups. Fifteen laboratories collaboratively studied a method for the quantitative ultraviolet determination of ephedrine sulfate in sirups. Ephedrine is separated from water-soluble impurities and strong acids by elution from a weakly basic Celite column. Further cleanup is accomplished by retention of the ephedrine on a weakly acidic column while the weak acids, weak bases, and organic-soluble neutral compounds are eluted. Ephedrine is eluted from the column after neutralization with NH3 and is converted to benzaldehyde via an on-column periodate reaction. The samples collaboratively studied consisted of 2 commericial ephedrine-containing sirups and 2 commercial non-ephedrine-containing sirups to which ephedrine was added. Recoveries for the spiked sirups averaged 100.7 and 100.3% for mixtures containing 2.5 and 5.0 mg ephedrine sulfate/ml, respectively. The means and standard deviations for the commercial preparations were 4.088 plus or minus 0.068 and 2.375 plus or minus 0.053 mg/ml. The method has been adopted as official first action and has been incorporated into the official method for phenylpropanolamine hydrochloride, 38.199-38.203."}
{"id": "PMID:238935", "title": "Mutations affecting glutamine synthetase activity in Salmonella typhimurium.", "content": "A positive selection procedure has been devised for isolating mutant strains of Salmonella typhimurium with altered glutamine synthetase activity. Mutants are derived from a histidine auxotroph by selecting for ability to grow on D-histidine as the sole histidine source. We hypothesize that the phenotype may be based on a regulatory increase in the activities of the D-histidine racemizing enzymes, but this has not been established. Spontaneous glutamine-requiring mutants isolated by the above selection procedure have two types of alterations in glutamine synthetase activity. Some have less than 10% of parent activity. Others have significant glutamine synthetase activity, but the enzyme have an altered response to divalent cations. Activity in mutants of the second type mimics that of highly adenylylated wild-type enzyme, which is believed to be in-active in vivo. Glutamine synthetase from one such mutant is more heat labile than wild-type enzyme, indicating that it is structurally altered. Mutations in all strains are probably in the glutamine synthetase structural gene (glnA). They are closely linked on the Salmonella chromosome and lie at about min 125. The mutants have normal glutamate dehydrogenase activity.", "contents": "Mutations affecting glutamine synthetase activity in Salmonella typhimurium. A positive selection procedure has been devised for isolating mutant strains of Salmonella typhimurium with altered glutamine synthetase activity. Mutants are derived from a histidine auxotroph by selecting for ability to grow on D-histidine as the sole histidine source. We hypothesize that the phenotype may be based on a regulatory increase in the activities of the D-histidine racemizing enzymes, but this has not been established. Spontaneous glutamine-requiring mutants isolated by the above selection procedure have two types of alterations in glutamine synthetase activity. Some have less than 10% of parent activity. Others have significant glutamine synthetase activity, but the enzyme have an altered response to divalent cations. Activity in mutants of the second type mimics that of highly adenylylated wild-type enzyme, which is believed to be in-active in vivo. Glutamine synthetase from one such mutant is more heat labile than wild-type enzyme, indicating that it is structurally altered. Mutations in all strains are probably in the glutamine synthetase structural gene (glnA). They are closely linked on the Salmonella chromosome and lie at about min 125. The mutants have normal glutamate dehydrogenase activity."}
{"id": "PMID:238936", "title": "L-Asparaginase of Saccharomyces cerevisiae: an extracellular Enzyme.", "content": "During recent studies conducted with suspensions of three strains of Saccharomyces cerevisiae, it was observed that ammonia was rapidly liberated when L-asparagine was added to the medium. Subsequent investigation has revealed that these strains of S. cerevisiae have an externally active asparaginase as well as an internally active one. The appearance of the external asparaginase is stimulated by nitrogen starvation, requires an available energy source, and is prevented by cycloheximide. The internal enzyme appears to be constitutive. The external activity is relatively insensitive to para-hydroxymercuribenzoate inhibition, whereas the internal activity is highly inhibited by this compound.", "contents": "L-Asparaginase of Saccharomyces cerevisiae: an extracellular Enzyme. During recent studies conducted with suspensions of three strains of Saccharomyces cerevisiae, it was observed that ammonia was rapidly liberated when L-asparagine was added to the medium. Subsequent investigation has revealed that these strains of S. cerevisiae have an externally active asparaginase as well as an internally active one. The appearance of the external asparaginase is stimulated by nitrogen starvation, requires an available energy source, and is prevented by cycloheximide. The internal enzyme appears to be constitutive. The external activity is relatively insensitive to para-hydroxymercuribenzoate inhibition, whereas the internal activity is highly inhibited by this compound."}
{"id": "PMID:238937", "title": "Gene order of the histidine utilization (hut) operons in Klebsiella aerogenes.", "content": "P1-sensitive mutants of Klebsiella aerogenes were isolated and the gene order of the hut region was then determined using P1-mediated transduction. The genes are located in the Klebsiella chromosome between gal and bio as in Salmonella typhimurium. The gene order, gal, hutI, hutG, hutC, huU, hutH, bio is also the same as that observed in S. typhimurium.", "contents": "Gene order of the histidine utilization (hut) operons in Klebsiella aerogenes. P1-sensitive mutants of Klebsiella aerogenes were isolated and the gene order of the hut region was then determined using P1-mediated transduction. The genes are located in the Klebsiella chromosome between gal and bio as in Salmonella typhimurium. The gene order, gal, hutI, hutG, hutC, huU, hutH, bio is also the same as that observed in S. typhimurium."}
{"id": "PMID:238938", "title": "Regulation of Glutamine Transport in Escherichia coli.", "content": "The formation of the high-affinity (Km equal to 0.2 muM) L-glutamine transport system of Escherichia coli strain 7 (Lin) appears to be subject to the same major control as the glutamine synthetase (EC 6.3.1.2) of this gram-negative organism. Culture of cells under nitrogen-limited conditions provides maximum derepression of both the glutamine synthetase and the glutamine transport system. Nutritional conditions providing a rich supply of ammonium salts or available sources of nitrogen, i.e., conditions which repress the formation of glutamine synthetase, provide three- and 20-fold repression, respectively, of the glutamine transport system. Culture of cells with glutamine supplements of 2 mM does not increase the repression of high-affinity glutamine transport system beyond the level observed in the absence of glutamine. A second kinetically distinct low-affinity component of glutamine. A second kinetically distinct low-affinity component of glutamine uptake is observed in cells cultured with a glutamine-depleted nutrient broth. This second component is associated with the appearance of glutaminase A (EC 3.5.1.2) and asparaginase I (EC 3.5.1.1), a periplasmic enzyme. Parallel changes were observed in the levels of the high-affinity glutamine transport system and the glutamine synthetase when cells were cultured with the carbon sources: glucose, glycerol, or succinate.", "contents": "Regulation of Glutamine Transport in Escherichia coli. The formation of the high-affinity (Km equal to 0.2 muM) L-glutamine transport system of Escherichia coli strain 7 (Lin) appears to be subject to the same major control as the glutamine synthetase (EC 6.3.1.2) of this gram-negative organism. Culture of cells under nitrogen-limited conditions provides maximum derepression of both the glutamine synthetase and the glutamine transport system. Nutritional conditions providing a rich supply of ammonium salts or available sources of nitrogen, i.e., conditions which repress the formation of glutamine synthetase, provide three- and 20-fold repression, respectively, of the glutamine transport system. Culture of cells with glutamine supplements of 2 mM does not increase the repression of high-affinity glutamine transport system beyond the level observed in the absence of glutamine. A second kinetically distinct low-affinity component of glutamine. A second kinetically distinct low-affinity component of glutamine uptake is observed in cells cultured with a glutamine-depleted nutrient broth. This second component is associated with the appearance of glutaminase A (EC 3.5.1.2) and asparaginase I (EC 3.5.1.1), a periplasmic enzyme. Parallel changes were observed in the levels of the high-affinity glutamine transport system and the glutamine synthetase when cells were cultured with the carbon sources: glucose, glycerol, or succinate."}
{"id": "PMID:238939", "title": "Aromatic amino acid transport in Yersinia pestis.", "content": "The uptake and concentration of aromatic amino acids by Yersinia pestis TJW was investigated using endogenously metabolizing cells. Transport activity did not depend on either protein synthesis or exogenously added energy sources such as glucose. Aromatic amino acids remained as the free, unaltered amino acid in the pool fraction. Phenylalanine and tryptophan transport obeyed Michaelis-Menten-like kinetics with apparent Km values of 6 x 10(-7) to 7.5 x 10(-7) and 2 x 10(-6) M, respectively. Tyrosine transport showed biphasic concentration-dependent kinetics that indicated a diffusion-like process above external tyrosine concentrations of 2 x 10(-6) M. Transport of each aromatic amino acid showed different pH and temperature optima. The pH (7.5 TO8) and temperature (27 C) optima for phenylalanine transport were similar to those for growth. Transport of each aromatic amino acid was characterized by Q10 values of approximately 2. Cross inhibition and exchange experiments between the aromatic amino acids and selected aromatic amino acid analogues revealed the existence of three transport systems: (i) tryptophan specific, (ii) phenylalanine specific with limited transport activity for tyrosine and tryptophan, and (iii) general aromatic system with some specificity for tyrosine. Analogue studies also showed that the minimal stereo and structural features for phenylalanine recognition were: (i) the L isomer, (ii) intact alpha amino and carboxy group, and (iii) unsubstituted aromatic ring. Aromatic amino acid transport was differentially inhibited by various sulfhydryl blocking reagents and energy inhibitors. Phenylalanine and tyrosine transport was inhibited by 2,4-dinitrophenol, potassium cyanide, and sodium azide. Phenylalanine transport showed greater sensitivity to inhibition by sulfhydryl blocking reagents, particularly N-ethylmaleimide, than did tyrosine transport. Tryptophan transport was not inhibited by either sulfhydryl reagents or sodium azide. The results on the selective inhibition of aromatic amino acid transport provide additional evidence for multiple transport systems . These results further suggest both specific mechanisms for carrier-mediated active transport and coupling to metabolic energy.", "contents": "Aromatic amino acid transport in Yersinia pestis. The uptake and concentration of aromatic amino acids by Yersinia pestis TJW was investigated using endogenously metabolizing cells. Transport activity did not depend on either protein synthesis or exogenously added energy sources such as glucose. Aromatic amino acids remained as the free, unaltered amino acid in the pool fraction. Phenylalanine and tryptophan transport obeyed Michaelis-Menten-like kinetics with apparent Km values of 6 x 10(-7) to 7.5 x 10(-7) and 2 x 10(-6) M, respectively. Tyrosine transport showed biphasic concentration-dependent kinetics that indicated a diffusion-like process above external tyrosine concentrations of 2 x 10(-6) M. Transport of each aromatic amino acid showed different pH and temperature optima. The pH (7.5 TO8) and temperature (27 C) optima for phenylalanine transport were similar to those for growth. Transport of each aromatic amino acid was characterized by Q10 values of approximately 2. Cross inhibition and exchange experiments between the aromatic amino acids and selected aromatic amino acid analogues revealed the existence of three transport systems: (i) tryptophan specific, (ii) phenylalanine specific with limited transport activity for tyrosine and tryptophan, and (iii) general aromatic system with some specificity for tyrosine. Analogue studies also showed that the minimal stereo and structural features for phenylalanine recognition were: (i) the L isomer, (ii) intact alpha amino and carboxy group, and (iii) unsubstituted aromatic ring. Aromatic amino acid transport was differentially inhibited by various sulfhydryl blocking reagents and energy inhibitors. Phenylalanine and tyrosine transport was inhibited by 2,4-dinitrophenol, potassium cyanide, and sodium azide. Phenylalanine transport showed greater sensitivity to inhibition by sulfhydryl blocking reagents, particularly N-ethylmaleimide, than did tyrosine transport. Tryptophan transport was not inhibited by either sulfhydryl reagents or sodium azide. The results on the selective inhibition of aromatic amino acid transport provide additional evidence for multiple transport systems . These results further suggest both specific mechanisms for carrier-mediated active transport and coupling to metabolic energy."}
{"id": "PMID:238940", "title": "Purification, characterization, and regulation of a nicotinamide adenine dinucleotide-dependent lactate dehydrogenase from Actinomyces viscosus.", "content": "A nicotinamide adenine dinucleotide-specific L-(+)-lactate dehydrogenase (LDH) (EC 1.11.27) from Actinomyces viscosus T-6-1600 was purified approximately 110-fold by a combination of diethylaminoethyl-cellulose and 0.5 M Agarose A column chromatography. The ldh was stable at 26 C, but was quite labile at temperatures below 5 C. The enzyme had a molecular weight of 100,000 +/- 10,000 as determined by 0.5 M Agarose molecular exclusion chromatography and showed optimum activity between pH 5.5 and 6.2. The A. viscosus LDH exhibited homotropic interactions with its substrate, pyruvate, and its coenzyme, reduced nicotinamide adenine dinucleotide, indicating multiple binding sites on the enzyme for these ligands with some degree of cooperative interaction between them. The enzyme was under negative control by adenosine 5'-triphosphate, and its kinetic response to the negative effector was sigmoidal in nature. Inorganic phosphate reversed the inhibition exerted on the A. viscosus LDH by adenosine. The 5'-triphosphate thermal stability at 65 C of the LDH from A. viscosus was increased in the presence of its negative effector, adenosine 5'-triphosphate, but was markedly decreased in the presence of its coenzyme, reduced nicotinamide adenine dinucleotide. The glycolytic intermediate, fructose-1,6-diphosphate, had no effect on the catalytic activity of the A. viscosus LDH at saturating pyruvate concentrations. However, fructose-1,6-diphosphate was a potent positive effector at low substrate concentrations. Thus the A. viscosus LDH is under positive control by fructose-1,6-diphosphate and inorganic phosphate, but under negative control by adenosine 5'-triphosphate.", "contents": "Purification, characterization, and regulation of a nicotinamide adenine dinucleotide-dependent lactate dehydrogenase from Actinomyces viscosus. A nicotinamide adenine dinucleotide-specific L-(+)-lactate dehydrogenase (LDH) (EC 1.11.27) from Actinomyces viscosus T-6-1600 was purified approximately 110-fold by a combination of diethylaminoethyl-cellulose and 0.5 M Agarose A column chromatography. The ldh was stable at 26 C, but was quite labile at temperatures below 5 C. The enzyme had a molecular weight of 100,000 +/- 10,000 as determined by 0.5 M Agarose molecular exclusion chromatography and showed optimum activity between pH 5.5 and 6.2. The A. viscosus LDH exhibited homotropic interactions with its substrate, pyruvate, and its coenzyme, reduced nicotinamide adenine dinucleotide, indicating multiple binding sites on the enzyme for these ligands with some degree of cooperative interaction between them. The enzyme was under negative control by adenosine 5'-triphosphate, and its kinetic response to the negative effector was sigmoidal in nature. Inorganic phosphate reversed the inhibition exerted on the A. viscosus LDH by adenosine. The 5'-triphosphate thermal stability at 65 C of the LDH from A. viscosus was increased in the presence of its negative effector, adenosine 5'-triphosphate, but was markedly decreased in the presence of its coenzyme, reduced nicotinamide adenine dinucleotide. The glycolytic intermediate, fructose-1,6-diphosphate, had no effect on the catalytic activity of the A. viscosus LDH at saturating pyruvate concentrations. However, fructose-1,6-diphosphate was a potent positive effector at low substrate concentrations. Thus the A. viscosus LDH is under positive control by fructose-1,6-diphosphate and inorganic phosphate, but under negative control by adenosine 5'-triphosphate."}
{"id": "PMID:238941", "title": "Striated fibers of the rho form of Mycoplasma: in vitro reassembly, composition, and structure.", "content": "The rho-form of Mycoplasma contains a striated, axial fiber and associated terminal structure. The presence of this organelle was correlated with the synthesis of two proteins, A and B, of molecular weights of approximately 85,000 and 26,000, respectively, each accounting for about 10% of the total cell protein. Their amino acid compositions showed them to have distinct polypeptide chains. After osmotic lysis of rho-form cells the organelles disappeared; protein A accompanied the membrane fraction, whereas protein B was partly released in soluble form. After lysis by Nonidet P-40 in a medium composed of 4 M glycerol, 50 mM phosphate, and 10 mM MgSO4 at pH 6 (GPM-6), the organelles were preserved and released with ultrastructure unchanged. Protein A was recovered in the soluble fraction and protein B in the particulate (crude fiber) fraction. Treatment of the crude fiber fraction with 0.5 M NaCl in GPM-6 or with a solution containing 4 M glycerol, 10 mM morpholinoethanesulfonate, and 1 mM ethylenediaminetetraacetate at pH 7.0 caused the fibers to disassemble into subunits. By subsequent changes in the ionic conditions and temperature it was possible to cause the subunits to reassemble into ordered aggregates having the same ultrastructure as the native rho-fibers. The optimum temperature for reassembly in the presence of 4 M glycerol was 37 C, the optimum pH was 6.5 to 7.0, and the presence of Mg-2+, replaceable by Ca-2+, SR-2+, or Ba-2+, was essential. Protein B was the only protein detected in the purified, reconsituted fibers.", "contents": "Striated fibers of the rho form of Mycoplasma: in vitro reassembly, composition, and structure. The rho-form of Mycoplasma contains a striated, axial fiber and associated terminal structure. The presence of this organelle was correlated with the synthesis of two proteins, A and B, of molecular weights of approximately 85,000 and 26,000, respectively, each accounting for about 10% of the total cell protein. Their amino acid compositions showed them to have distinct polypeptide chains. After osmotic lysis of rho-form cells the organelles disappeared; protein A accompanied the membrane fraction, whereas protein B was partly released in soluble form. After lysis by Nonidet P-40 in a medium composed of 4 M glycerol, 50 mM phosphate, and 10 mM MgSO4 at pH 6 (GPM-6), the organelles were preserved and released with ultrastructure unchanged. Protein A was recovered in the soluble fraction and protein B in the particulate (crude fiber) fraction. Treatment of the crude fiber fraction with 0.5 M NaCl in GPM-6 or with a solution containing 4 M glycerol, 10 mM morpholinoethanesulfonate, and 1 mM ethylenediaminetetraacetate at pH 7.0 caused the fibers to disassemble into subunits. By subsequent changes in the ionic conditions and temperature it was possible to cause the subunits to reassemble into ordered aggregates having the same ultrastructure as the native rho-fibers. The optimum temperature for reassembly in the presence of 4 M glycerol was 37 C, the optimum pH was 6.5 to 7.0, and the presence of Mg-2+, replaceable by Ca-2+, SR-2+, or Ba-2+, was essential. Protein B was the only protein detected in the purified, reconsituted fibers."}
{"id": "PMID:238942", "title": "Purification and properties of glutamate dehydrogenase from a thermophilic bacillus.", "content": "A 250- to 300-fold purification of a nicotinamide adenine denucleotide phosphate (NADP)-dependent glutamate dehydrogenase (GDH, E.C. 1.4.1.4) with a yield of 60% from a thermophilic bacillus is described. More than one NADP-specific GDH was detected by polyacrylamide gel electrophoresis. The enzyme is of high molecular weight (approximately 2 X 10-6), similar to that of the beef and frog liver GDH. The pI of the thermophilic GDH is at pH 5.24. The enzyme is highly thermostable at the pH range of 5.8 to 9.0. The purified GDH, unlike the crude enzyme, was very labile at subzero temperatures. An unidentified factor(s) from the crude cell-free extract prevented the inactivation of the purified GDH at -70 C. Various reactants of the GDH system and D-glutamate also protected, to some extent, the enzyme from inactivation at -70 C. From the Michaelis constants for glutamate (1.1 X 10-2M), NADP (3 X 10-4M), ammonia (2.1 X 10-2M), alpha-ketoglutarate (1.3 X 10-3M), and reduced NADP (5.3 X 10-5M), it is suggested that the enzyme catalyzes in vivo the formation of glutamate from ammonia and alpha-ketoglutarate. The amination of alpha-ketoglutarate and deamination of glutamate by the thermophilic GDH are optimal at the pH values of 7.2 and 8.4, respectively.", "contents": "Purification and properties of glutamate dehydrogenase from a thermophilic bacillus. A 250- to 300-fold purification of a nicotinamide adenine denucleotide phosphate (NADP)-dependent glutamate dehydrogenase (GDH, E.C. 1.4.1.4) with a yield of 60% from a thermophilic bacillus is described. More than one NADP-specific GDH was detected by polyacrylamide gel electrophoresis. The enzyme is of high molecular weight (approximately 2 X 10-6), similar to that of the beef and frog liver GDH. The pI of the thermophilic GDH is at pH 5.24. The enzyme is highly thermostable at the pH range of 5.8 to 9.0. The purified GDH, unlike the crude enzyme, was very labile at subzero temperatures. An unidentified factor(s) from the crude cell-free extract prevented the inactivation of the purified GDH at -70 C. Various reactants of the GDH system and D-glutamate also protected, to some extent, the enzyme from inactivation at -70 C. From the Michaelis constants for glutamate (1.1 X 10-2M), NADP (3 X 10-4M), ammonia (2.1 X 10-2M), alpha-ketoglutarate (1.3 X 10-3M), and reduced NADP (5.3 X 10-5M), it is suggested that the enzyme catalyzes in vivo the formation of glutamate from ammonia and alpha-ketoglutarate. The amination of alpha-ketoglutarate and deamination of glutamate by the thermophilic GDH are optimal at the pH values of 7.2 and 8.4, respectively."}
{"id": "PMID:238943", "title": "Three yeast proteins that specifically inhibit yeast proteases A, B, and C.", "content": "Baker's yeast was found to contain inhibitors of yeast proteases A and C. These two proteins were partially purified, characterized, and compared with the previously described inhibitor of protease B. The A and B inhibitors were very thermostable and were extracted from intact yeast cells at 9k C. The A inhibitor appeared to be a protein with a molecular weight of about 22,000 which could be dissociated into two monomers or chains, both of which had a molecular weight of approximately 11,000. The protease C (carboxypeptidase Y)-inhibitor complex was purified and then partially disociated on an ion-exchange column. The free protease C inhibitor was very unstable, possibly because of destruction by a contaminating protease. Each inhibitor was specific for its corresponding protease and each inhibition was competitive. Whereas proteases A, B, and C destroyed the B inhibitor, only protease B had a pronounced destructive effect on the protease A inhibitor. Pepstatin was found to be a selective inhibitor of protease A, whereas chymostatin and antipain specifically inhibited protease B.", "contents": "Three yeast proteins that specifically inhibit yeast proteases A, B, and C. Baker's yeast was found to contain inhibitors of yeast proteases A and C. These two proteins were partially purified, characterized, and compared with the previously described inhibitor of protease B. The A and B inhibitors were very thermostable and were extracted from intact yeast cells at 9k C. The A inhibitor appeared to be a protein with a molecular weight of about 22,000 which could be dissociated into two monomers or chains, both of which had a molecular weight of approximately 11,000. The protease C (carboxypeptidase Y)-inhibitor complex was purified and then partially disociated on an ion-exchange column. The free protease C inhibitor was very unstable, possibly because of destruction by a contaminating protease. Each inhibitor was specific for its corresponding protease and each inhibition was competitive. Whereas proteases A, B, and C destroyed the B inhibitor, only protease B had a pronounced destructive effect on the protease A inhibitor. Pepstatin was found to be a selective inhibitor of protease A, whereas chymostatin and antipain specifically inhibited protease B."}
{"id": "PMID:238944", "title": "Purification and regulatory properties of pyruvate kinase from Veillonella parvula.", "content": "The nonglycolytic, anaerobic organism Veillonella parvula M4 has been shown to contain an active pyruvate kinase. The enzyme was purified 126-fold and was shown by disc-gel electrophoresis to contain only two faint contaminating bands. The purified enzyme had a pH optimum of 7.0 in the forward direction and exhibited sigmoidal kinetics at varying concentrations o-f phosphoenol pyruvate (PEP), adenosine 5'-monophosphate (AMP), and Mg-2+ ions with S0.5 values of 1.5, 2.0, and 2.4 mM, respectively. Substrate inhibition was observed above 4 m PEP. Hill plots gave slope values (n) of 4.4 (PEP), 2.8 (adenosine 5'-diphosphate), and 2.0 (Mg-2+), indicating a high degree of cooperativity. The enzyme was inhibited non-competitively by adenosine 5'-triphosphate (Ki = 3.4 mM), and this inhibition was only slightly affected by increasing concentration of Mg-2+ ions to 30 mM. Competitive inhibition was observed with 3-phosphoglycerate, malate, and 2,3-diphosphoglycerate but only at higher inhibitor concentrations. The enzyme was activated by glucose-6-phosphate (P), fructose-6-P, fructose-1,6-diphosphate (P2), dihydroxyacetone-P, and AMP; the Hill coefficients were 2.2, 1.8, 1.5, 2.1, and 2.0, respectively. The presence of each these metabolites caused substrate velocity curves to change from sigmoidal to hyperbolic curves, and each was accompanied by an increase in the maximum activity, e.g., AMP greater than fructose-1,6-P2 greater than dihydroxyacetone-P greater than glucose-6-P greater than fructose-6-P. The activation constants for fructose-1,6-P2, AMP, and glucose-6-P were 0.3, 1.1, and 5.3 mM, respectively. The effect of 5 mM fructose-1,6-P2 was significantly different from the other compounds in that this metabolite was inhibitory between 1.2 and 3 mM PEP. Above this concentration, fructose-1,6-P2 activated the enzyme and abolished substrate inhibition by PEP. The enzyme was not affected by glucose, glyceraldehyde-3-P, 2-phosphoglycerate, lactate, malate, fumerate, succinate, and cyclic AMP. The results suggest that the pyruvate kinase from V. parvula M4 plays a central role in the control of gluconeogenesis in this organism by regulating the concentration of PEP.", "contents": "Purification and regulatory properties of pyruvate kinase from Veillonella parvula. The nonglycolytic, anaerobic organism Veillonella parvula M4 has been shown to contain an active pyruvate kinase. The enzyme was purified 126-fold and was shown by disc-gel electrophoresis to contain only two faint contaminating bands. The purified enzyme had a pH optimum of 7.0 in the forward direction and exhibited sigmoidal kinetics at varying concentrations o-f phosphoenol pyruvate (PEP), adenosine 5'-monophosphate (AMP), and Mg-2+ ions with S0.5 values of 1.5, 2.0, and 2.4 mM, respectively. Substrate inhibition was observed above 4 m PEP. Hill plots gave slope values (n) of 4.4 (PEP), 2.8 (adenosine 5'-diphosphate), and 2.0 (Mg-2+), indicating a high degree of cooperativity. The enzyme was inhibited non-competitively by adenosine 5'-triphosphate (Ki = 3.4 mM), and this inhibition was only slightly affected by increasing concentration of Mg-2+ ions to 30 mM. Competitive inhibition was observed with 3-phosphoglycerate, malate, and 2,3-diphosphoglycerate but only at higher inhibitor concentrations. The enzyme was activated by glucose-6-phosphate (P), fructose-6-P, fructose-1,6-diphosphate (P2), dihydroxyacetone-P, and AMP; the Hill coefficients were 2.2, 1.8, 1.5, 2.1, and 2.0, respectively. The presence of each these metabolites caused substrate velocity curves to change from sigmoidal to hyperbolic curves, and each was accompanied by an increase in the maximum activity, e.g., AMP greater than fructose-1,6-P2 greater than dihydroxyacetone-P greater than glucose-6-P greater than fructose-6-P. The activation constants for fructose-1,6-P2, AMP, and glucose-6-P were 0.3, 1.1, and 5.3 mM, respectively. The effect of 5 mM fructose-1,6-P2 was significantly different from the other compounds in that this metabolite was inhibitory between 1.2 and 3 mM PEP. Above this concentration, fructose-1,6-P2 activated the enzyme and abolished substrate inhibition by PEP. The enzyme was not affected by glucose, glyceraldehyde-3-P, 2-phosphoglycerate, lactate, malate, fumerate, succinate, and cyclic AMP. The results suggest that the pyruvate kinase from V. parvula M4 plays a central role in the control of gluconeogenesis in this organism by regulating the concentration of PEP."}
{"id": "PMID:238945", "title": "Cell surface-located deoxyribonucleic acid receptors in transformable pneumococci.", "content": "We studied deoxyribonucleic acid (DNA) binding in transformable pneumococci. The relevant findings are as follows. (i) At least half of the DNA Molecules adsorbed to competent cells in the growth medium are attached to sites on the protoplast membrane. (ii) Most of the DNA bound to live competent cells in the presence of glucose is not released by moderate shear or by autolysin treatment. In contrast, most of the DNA adsorbed to competent cells in the absence of glucose is shear and autolysin sensitive. (iii) The presence of binding sites resembling in properties the sites in live competent cells can be demonstrated in wall-membrane complexes. Most of these sites are lost during preparation of cell walls and protoplasts. It is suggested that the DNA-binding site is a membrane component (protein?) Stabilized by polysaccharide (cell Wall) material. (IV) Mechanical or enzymatic damage to the cell wall or change in the ionic conditions can induce DNA binding (and surface-nuclease activity) in the incompetent pneumococci. However, such cells still show neither genetic transformation nor extensive nuclease-resistant binding of DNA. It is suggested that both competent and incompetent cells contain a large number of sequestered DNA-binding sites that can be unmasked by several experimental conditions. Induction of the competent state by the competence activator protein may involve an endogenous unmasking process.", "contents": "Cell surface-located deoxyribonucleic acid receptors in transformable pneumococci. We studied deoxyribonucleic acid (DNA) binding in transformable pneumococci. The relevant findings are as follows. (i) At least half of the DNA Molecules adsorbed to competent cells in the growth medium are attached to sites on the protoplast membrane. (ii) Most of the DNA bound to live competent cells in the presence of glucose is not released by moderate shear or by autolysin treatment. In contrast, most of the DNA adsorbed to competent cells in the absence of glucose is shear and autolysin sensitive. (iii) The presence of binding sites resembling in properties the sites in live competent cells can be demonstrated in wall-membrane complexes. Most of these sites are lost during preparation of cell walls and protoplasts. It is suggested that the DNA-binding site is a membrane component (protein?) Stabilized by polysaccharide (cell Wall) material. (IV) Mechanical or enzymatic damage to the cell wall or change in the ionic conditions can induce DNA binding (and surface-nuclease activity) in the incompetent pneumococci. However, such cells still show neither genetic transformation nor extensive nuclease-resistant binding of DNA. It is suggested that both competent and incompetent cells contain a large number of sequestered DNA-binding sites that can be unmasked by several experimental conditions. Induction of the competent state by the competence activator protein may involve an endogenous unmasking process."}
{"id": "PMID:238946", "title": "Oxidation of C1 Compounds by Particulate fractions from Methylococcus capsulatus: distribution and properties of methane-dependent reduced nicotinamide adenine dinucleotide oxidase (methane hydroxylase).", "content": "Cell-free particulate fractions of extracts from the obligate methylotroph Methylococcus capsulatus catalyze the reduced nicotinamide adenine dinucleotide (NADH) and O2-dependent oxidation of methane (methane hydroxylase). The only oxidation product detected was formate. These preparations also catalyze the oxidation of methanol and formaldehyde to formate in the presence or absence of phenazine methosulphate with oxygen as the terminal electron acceptor. Methane hydroxylase activity cannot be reproducibly obtained from disintegrated cell suspensions even though the whole cells actively respired when methane was presented as a substrate. Varying the disintegration method or extraction medium had no significant effect on the activities obtained. When active particles were obtained, hydroxylase activity was stable at 0 C for days. Methane hydroxylase assays were made by measuring the methane-dependent oxidation of NADH by O2. In separate experiments, methane consumption and the accumulation of formate were also demonstrated. Formate is not oxidized by these particulate fractions. The effects of particle concentration, temperature, pH, and phosphate concentration on enzymic activity are described. Ethane is utilized in the presence of NADH and O2. The stoichiometric relationships of the reaction(s) with methane as substrate were not established since (i) the presumed initial product, methanol, is also oxidized to formate, and (ii) the contribution that NADH oxidase activity makes to the observed consumption of reactants could not be assessed in the presence of methane. Studies with known inhibitors of electron transport systems indicate that the path of electron flow from NADH to oxygen is different for the NADH oxidase, methane hydroxylase, and methanol oxidase activities.", "contents": "Oxidation of C1 Compounds by Particulate fractions from Methylococcus capsulatus: distribution and properties of methane-dependent reduced nicotinamide adenine dinucleotide oxidase (methane hydroxylase). Cell-free particulate fractions of extracts from the obligate methylotroph Methylococcus capsulatus catalyze the reduced nicotinamide adenine dinucleotide (NADH) and O2-dependent oxidation of methane (methane hydroxylase). The only oxidation product detected was formate. These preparations also catalyze the oxidation of methanol and formaldehyde to formate in the presence or absence of phenazine methosulphate with oxygen as the terminal electron acceptor. Methane hydroxylase activity cannot be reproducibly obtained from disintegrated cell suspensions even though the whole cells actively respired when methane was presented as a substrate. Varying the disintegration method or extraction medium had no significant effect on the activities obtained. When active particles were obtained, hydroxylase activity was stable at 0 C for days. Methane hydroxylase assays were made by measuring the methane-dependent oxidation of NADH by O2. In separate experiments, methane consumption and the accumulation of formate were also demonstrated. Formate is not oxidized by these particulate fractions. The effects of particle concentration, temperature, pH, and phosphate concentration on enzymic activity are described. Ethane is utilized in the presence of NADH and O2. The stoichiometric relationships of the reaction(s) with methane as substrate were not established since (i) the presumed initial product, methanol, is also oxidized to formate, and (ii) the contribution that NADH oxidase activity makes to the observed consumption of reactants could not be assessed in the presence of methane. Studies with known inhibitors of electron transport systems indicate that the path of electron flow from NADH to oxygen is different for the NADH oxidase, methane hydroxylase, and methanol oxidase activities."}
{"id": "PMID:238947", "title": "Oxidation of C1 compounds by particulate fractions from Methylococcus capsulatus: properties of methanol oxidase and methanol dehydrogenase.", "content": "Methanol (and formaldehyde) oxidizing activities in crude extracts of Methylococcus capsulatus are associated mainly with particulate fractions sedimenting between 3,000 and 40,000 X g. Most of the phenazine methosulfate (PMS)-dependent methanol (and formaldehyde) dehydrogenase activity observed resides in the soluble fraction but represents only 40% of the total (PMS dependent plus independent) activity. Both PMS-dependent methanol dehydrogenase activity and PMS-independent methanol oxidase activity are found in particulate fractions, and the PMS-dependent dehydrogenase is easily solubilized by treatment with certain phospholipases or detergents. The properties of the PMS-dependent dehydrogenase activities in the soluble fraction and that solubilized from the particles suggested that they may be identical proteins. Their pH optima, temperature dependence, thermolabilities, and sensitivities to the presence of specific antisera were indistinguishable. Homogeneous preparations of the enzyme proteins obtained from the soluble fractions of extracts and the particulate fractions solubilized by detergents had similar: (i) electrophoretic mobilities in native and denatured states (subunit size in sodium dodecyl sulfate  62,000 daltons); (ii) molecular radii under native conditions, (iii) visible absorption spectra, lambdamax 350 nm, (iv) kinetic constants for methanol and formaldehyde; (v) substrate specificity; and (vi) immunological characteristics--antisera to each enzyme preparation showed precipitin lines of identity to either of the enzymes. It is suggested that the major site of methanol and formaldehyde oxidation in M. capsulatus occurs on the intracytoplasmic membranes in vivo and is coupled to oxygen reduction.", "contents": "Oxidation of C1 compounds by particulate fractions from Methylococcus capsulatus: properties of methanol oxidase and methanol dehydrogenase. Methanol (and formaldehyde) oxidizing activities in crude extracts of Methylococcus capsulatus are associated mainly with particulate fractions sedimenting between 3,000 and 40,000 X g. Most of the phenazine methosulfate (PMS)-dependent methanol (and formaldehyde) dehydrogenase activity observed resides in the soluble fraction but represents only 40% of the total (PMS dependent plus independent) activity. Both PMS-dependent methanol dehydrogenase activity and PMS-independent methanol oxidase activity are found in particulate fractions, and the PMS-dependent dehydrogenase is easily solubilized by treatment with certain phospholipases or detergents. The properties of the PMS-dependent dehydrogenase activities in the soluble fraction and that solubilized from the particles suggested that they may be identical proteins. Their pH optima, temperature dependence, thermolabilities, and sensitivities to the presence of specific antisera were indistinguishable. Homogeneous preparations of the enzyme proteins obtained from the soluble fractions of extracts and the particulate fractions solubilized by detergents had similar: (i) electrophoretic mobilities in native and denatured states (subunit size in sodium dodecyl sulfate  62,000 daltons); (ii) molecular radii under native conditions, (iii) visible absorption spectra, lambdamax 350 nm, (iv) kinetic constants for methanol and formaldehyde; (v) substrate specificity; and (vi) immunological characteristics--antisera to each enzyme preparation showed precipitin lines of identity to either of the enzymes. It is suggested that the major site of methanol and formaldehyde oxidation in M. capsulatus occurs on the intracytoplasmic membranes in vivo and is coupled to oxygen reduction."}
{"id": "PMID:238948", "title": "Calcification by Candida albicans.", "content": "Candida albicans was grown in a chamically defined medium in which certain microorganisms are known to calcify. The fungus developed calcium phosphate deposits with the same X-ray diffraction maxima as biological apatite.", "contents": "Calcification by Candida albicans. Candida albicans was grown in a chamically defined medium in which certain microorganisms are known to calcify. The fungus developed calcium phosphate deposits with the same X-ray diffraction maxima as biological apatite."}
{"id": "PMID:238949", "title": "Dual role for N-2-acetylornithine 5-aminotransferase from Pseudomonas aeruginosa in arginine biosynthesis and arginine catabolism.", "content": "In Pseudomonas aeruginosa N-2-acetylornithine 5-aminotransferase (ACOAT), the fourth enzyme of arginine biosynthesis is induced about 15-fold by cultivating the organism on a medium with L-arginine as the sole carbon and nitrogen source. Synthesis of the enzyme is subject to catabolite repression and nitrogen source. Synthesis of the enzyme is subject to catabolite repression by a variety of carbon sources. ACOAT from strain PAO 1 was purified over 40-fold to electrophoretic homogeneity. A molecular weight of approximately 110,000 was obtained by thin-layer gel filtration. Electrophoresis in sodium dodecyl sulfate gels gave a single band corresponding to a molecular weight of 55,000. Purified ACOAT catalyzes the transamination of N-2-acetyl-L-ornithine as well as of L-ornithine with 2-oxoglutarate (Km values of 1.1, 10.0, and 0.7 mM, respectively). With N-2-acetyl-L-ornithine as amino donor, the pH-optimum of the enzymatic reaction is 8.5; with L-ornithine as amino donor, 9.5. The catalytic properties of ACOAT as well as the regulation of its synthesis indicate that in P. aeruginosa this enzyme functions in the biosynthesis as well as in the catabolism of L-arginine.", "contents": "Dual role for N-2-acetylornithine 5-aminotransferase from Pseudomonas aeruginosa in arginine biosynthesis and arginine catabolism. In Pseudomonas aeruginosa N-2-acetylornithine 5-aminotransferase (ACOAT), the fourth enzyme of arginine biosynthesis is induced about 15-fold by cultivating the organism on a medium with L-arginine as the sole carbon and nitrogen source. Synthesis of the enzyme is subject to catabolite repression and nitrogen source. Synthesis of the enzyme is subject to catabolite repression by a variety of carbon sources. ACOAT from strain PAO 1 was purified over 40-fold to electrophoretic homogeneity. A molecular weight of approximately 110,000 was obtained by thin-layer gel filtration. Electrophoresis in sodium dodecyl sulfate gels gave a single band corresponding to a molecular weight of 55,000. Purified ACOAT catalyzes the transamination of N-2-acetyl-L-ornithine as well as of L-ornithine with 2-oxoglutarate (Km values of 1.1, 10.0, and 0.7 mM, respectively). With N-2-acetyl-L-ornithine as amino donor, the pH-optimum of the enzymatic reaction is 8.5; with L-ornithine as amino donor, 9.5. The catalytic properties of ACOAT as well as the regulation of its synthesis indicate that in P. aeruginosa this enzyme functions in the biosynthesis as well as in the catabolism of L-arginine."}
{"id": "PMID:238950", "title": "Enzymes involved in the assimilation of one-carbon units by Pseudomonas MS.", "content": "Pseudomonas MS can grow on methylamine and a number of other compounds containing C1 units as a sole source of carbon and energy. Assimilation of carbon into cell material occurs via the \"serine pathway\" since enzymes of this pathway are induced after growth on methylamine, but not malate or acetate. A mutant has been isolated which is unable to grow on methylamine or any other related substrate providing C1 units. This mutant is also unable to grow on acetate. Measurment of enzyme activities in cell-free extracts of wild-type cells showed that growth on methylamine caused induction of isocitrate lyase, a key enzyme in the glyoxylate cycle. The mutant organism lacks malate lyase, a key enzyme of the serine pathway, and isocitrate lyase as well. These results suggest that utilization of C1 units by Pseudomonas MS results in the net accumulation of acetate which is then assimilated into cell material via the glyoxylate cycle.", "contents": "Enzymes involved in the assimilation of one-carbon units by Pseudomonas MS. Pseudomonas MS can grow on methylamine and a number of other compounds containing C1 units as a sole source of carbon and energy. Assimilation of carbon into cell material occurs via the \"serine pathway\" since enzymes of this pathway are induced after growth on methylamine, but not malate or acetate. A mutant has been isolated which is unable to grow on methylamine or any other related substrate providing C1 units. This mutant is also unable to grow on acetate. Measurment of enzyme activities in cell-free extracts of wild-type cells showed that growth on methylamine caused induction of isocitrate lyase, a key enzyme in the glyoxylate cycle. The mutant organism lacks malate lyase, a key enzyme of the serine pathway, and isocitrate lyase as well. These results suggest that utilization of C1 units by Pseudomonas MS results in the net accumulation of acetate which is then assimilated into cell material via the glyoxylate cycle."}
{"id": "PMID:238951", "title": "Transport of L-4-azaleucine in Escherichia coli.", "content": "The uptake of L-4-azaleucine was examined in Escherichia coli K-12 strains to determine the systems that serve for its accumulation. L-4=Azaleucine in radio-labeled form was synthesized and resolved by the action of hog kidney N-acylamino-acid amidohydrolase (EC 3.5.1.B) on the racemic alpha-N-acetyl derivative of DL-[dimethyl-14C]4-azaleucine. L-4-Azaleucine is taken up in E. coli by energy-dependent processes that are sensitive to changes in the pH and to inhibition by leucine and the aromatic amino acids. Although a single set of kinetic parameters was obtained by kinetic experiments, other evidence indicates that transport systems for both the aromatic and the branched-chain amino acids serve for azaleucine. Azaleucine uptake in strain EO317, with a mutation leading to derepression and constitutive expression of branched-chain amino acid (LIV) transport and binding proteins, was not repressed by growth with leucine as it was in parental strain EO300. Lesions in the aromatic amino acid transport system, aroP, also led to changes in the regulation of azaleucine uptake activity when cells were grown on phenylalanine. Experiments on the specificity of azaleucine uptake and exchange experiments with leucine and phenylalanine support the hypothesis that both LIV and aroP systems transport azaleucine. The ability of external azaleucine to exchange rapidly with intracellular leucine may be an important contributor to azaleucine toxicity. We conclude from these and other studies that at least four other process may affect azaleucine sensitivity: the level of branched-chain amino acid biosynthetic enzymes; the level of leucine, isoleucine, and valine transport systems; the level of the aromatic amino acid, aroP, uptake system; and, possibly, the ability of the cell to racemize D and L amino acids. The relative importance of these processes in azaleucine sensitivity under various conditions is not known precisely.", "contents": "Transport of L-4-azaleucine in Escherichia coli. The uptake of L-4-azaleucine was examined in Escherichia coli K-12 strains to determine the systems that serve for its accumulation. L-4=Azaleucine in radio-labeled form was synthesized and resolved by the action of hog kidney N-acylamino-acid amidohydrolase (EC 3.5.1.B) on the racemic alpha-N-acetyl derivative of DL-[dimethyl-14C]4-azaleucine. L-4-Azaleucine is taken up in E. coli by energy-dependent processes that are sensitive to changes in the pH and to inhibition by leucine and the aromatic amino acids. Although a single set of kinetic parameters was obtained by kinetic experiments, other evidence indicates that transport systems for both the aromatic and the branched-chain amino acids serve for azaleucine. Azaleucine uptake in strain EO317, with a mutation leading to derepression and constitutive expression of branched-chain amino acid (LIV) transport and binding proteins, was not repressed by growth with leucine as it was in parental strain EO300. Lesions in the aromatic amino acid transport system, aroP, also led to changes in the regulation of azaleucine uptake activity when cells were grown on phenylalanine. Experiments on the specificity of azaleucine uptake and exchange experiments with leucine and phenylalanine support the hypothesis that both LIV and aroP systems transport azaleucine. The ability of external azaleucine to exchange rapidly with intracellular leucine may be an important contributor to azaleucine toxicity. We conclude from these and other studies that at least four other process may affect azaleucine sensitivity: the level of branched-chain amino acid biosynthetic enzymes; the level of leucine, isoleucine, and valine transport systems; the level of the aromatic amino acid, aroP, uptake system; and, possibly, the ability of the cell to racemize D and L amino acids. The relative importance of these processes in azaleucine sensitivity under various conditions is not known precisely."}
{"id": "PMID:238952", "title": "Prosthecae of Asticcacaulis biprosthecum: system for the study of membrane transport.", "content": "Prosthecae removed from cells of Asticcacaulis biprosthecum were examined for their ability to accumulate proline, alanine, aspartate, glutamate, and glucose against a concentration gradient. The transport of all of these compounds into prosthecae was stimulated by the nonphysiological electron donors phenazine methosulfate and N,N,N',N'-tetramethyl-p-phenylene diamine dihydrochloride. Reduced pyridine nucleotides caused very slight stimulation of transport of proline and glucose. Other physiological electron donors did not stimulate uptake. Evidence is presented indicating that the failure of certain potential electron donors to drive respiratory chain-linked transport is due to the inabilityof these compounds to enter prosthecae rather than to the absence of enzymes for their oxidation in prosthecae. Inhibition of respiration and uncouplers of oxidative phosphorylation, with the exception of arsenate, inhibit active transport systems of prosthecae.", "contents": "Prosthecae of Asticcacaulis biprosthecum: system for the study of membrane transport. Prosthecae removed from cells of Asticcacaulis biprosthecum were examined for their ability to accumulate proline, alanine, aspartate, glutamate, and glucose against a concentration gradient. The transport of all of these compounds into prosthecae was stimulated by the nonphysiological electron donors phenazine methosulfate and N,N,N',N'-tetramethyl-p-phenylene diamine dihydrochloride. Reduced pyridine nucleotides caused very slight stimulation of transport of proline and glucose. Other physiological electron donors did not stimulate uptake. Evidence is presented indicating that the failure of certain potential electron donors to drive respiratory chain-linked transport is due to the inabilityof these compounds to enter prosthecae rather than to the absence of enzymes for their oxidation in prosthecae. Inhibition of respiration and uncouplers of oxidative phosphorylation, with the exception of arsenate, inhibit active transport systems of prosthecae."}
{"id": "PMID:238953", "title": "Regulation of the lysine biosynthetic pathway in Escherichia coli K-12: isolation of a cis-dominant constitutive mutant for AK III synthesis.", "content": "A method for isolating regulatory mutants for the synthesis of lysine biosynthetic enzymes in Escherichia coli is described. One of them is identified as a cis-dominant constitutive mutant for the synthesis of the lysine-sensitive asportokinase AK III (lysC gene).", "contents": "Regulation of the lysine biosynthetic pathway in Escherichia coli K-12: isolation of a cis-dominant constitutive mutant for AK III synthesis. A method for isolating regulatory mutants for the synthesis of lysine biosynthetic enzymes in Escherichia coli is described. One of them is identified as a cis-dominant constitutive mutant for the synthesis of the lysine-sensitive asportokinase AK III (lysC gene)."}
{"id": "PMID:238954", "title": "Regulation of nitrogen metabolism in Escherichia coli and Klebsiella aerogenes: studies with the continuous-culture technique.", "content": "Ammonia-nitrogen-limited continuous cultures of Escherichia coli and Klebsiella aerogenes contain induced levels of glutamine synthetase that is deadenylyated (i.e., fully active). In the presence of excess ammonia or glutamate in glucose-limited cultures of E. coli, glutamine synthetase is repressed and adenylylated (inactive). The average state of adenylylation (n) is a linear function of the specific growth rate. At low specific growth rates, glutamine synthetase is adenylylated; as the specific growth rate increases, n decreases, approaching 0 to 2 at rapid growth rates. The average state of adenylylation correlates well with the intracellular concentrations and ratios of alpha-ketoglutarate and glutamine, which are key effectors in the adenylylation-deadenylylation systems. E. coli and K. aerogenes differ markedly in their growth yields, growth rates, and enzymatic composition during nitrogen limitation. The data suggest that, unlike K. aerogenes, E. coli W uses glutamate dehydrogenase to incorporate ammonia during nitrogen limitation. In E. coli, glutamate dehydrogenase is progressively induced during nitrogen limitation when mu (growth rate) approaches mumax. In contrast, in K. aerogenes glutamate dehydrogenase is repressed during nitrogen limitation, whereas glutamate synthase, an alternative supplier of glutamate to the cell, is induced. Data are presented that support the regulatory schemes proposed for the control of glutamine synthetase activity by induction-repression phenomena and adenylylation-deadenylylation reaction. We propose that the intracellular ratio of alpha-ketoglutarate to glutamine may be the most important physiological parameter in determining the activity of glutamine synthetase.", "contents": "Regulation of nitrogen metabolism in Escherichia coli and Klebsiella aerogenes: studies with the continuous-culture technique. Ammonia-nitrogen-limited continuous cultures of Escherichia coli and Klebsiella aerogenes contain induced levels of glutamine synthetase that is deadenylyated (i.e., fully active). In the presence of excess ammonia or glutamate in glucose-limited cultures of E. coli, glutamine synthetase is repressed and adenylylated (inactive). The average state of adenylylation (n) is a linear function of the specific growth rate. At low specific growth rates, glutamine synthetase is adenylylated; as the specific growth rate increases, n decreases, approaching 0 to 2 at rapid growth rates. The average state of adenylylation correlates well with the intracellular concentrations and ratios of alpha-ketoglutarate and glutamine, which are key effectors in the adenylylation-deadenylylation systems. E. coli and K. aerogenes differ markedly in their growth yields, growth rates, and enzymatic composition during nitrogen limitation. The data suggest that, unlike K. aerogenes, E. coli W uses glutamate dehydrogenase to incorporate ammonia during nitrogen limitation. In E. coli, glutamate dehydrogenase is progressively induced during nitrogen limitation when mu (growth rate) approaches mumax. In contrast, in K. aerogenes glutamate dehydrogenase is repressed during nitrogen limitation, whereas glutamate synthase, an alternative supplier of glutamate to the cell, is induced. Data are presented that support the regulatory schemes proposed for the control of glutamine synthetase activity by induction-repression phenomena and adenylylation-deadenylylation reaction. We propose that the intracellular ratio of alpha-ketoglutarate to glutamine may be the most important physiological parameter in determining the activity of glutamine synthetase."}
{"id": "PMID:238955", "title": "Regulation of catalase synthesis in Salmonella typhimurium.", "content": "The specific activity of catalase in Salmonella typhimurium and other enteric bacteria decreased during the logarithmic phase of growth and increased at the onset and during the stationary phase. The increase in catalase synthesis at the end of the exponential phase in S. typhimurium cells coincided with the lowest pH value reached by the culture. Maintenance of the pH at a constant neutral value did not alter the typical pattern of synthesis in contradiction of the results previously reported (McCarthy and Hinshelwood. 1959). A sudden decrease in the pH value of an S. typhimurium culture during exponential growth by addition of HC1 did not cause an alteration in the catalase synthesis pattern. Addition of hydrogen peroxide to S. typhimurium cultures within the range 1 muM TO 2MM during the exponential growth phase stimulated catalase synthesis. The extent of catalase synthesis depended on the concentration of hydrogen peroxide; the maximum stimulation was observed at 80 muM. Increased catalase synthesis was not detected for 10 to 15 min after hydrogen peroxide addition. Hydrogen peroxide was produced by S. typhimurium cultures during the exponential and stationary growth phases. However, no direct relationship between hydrogen peroxide accumulation and synthesis of catalase was observed.", "contents": "Regulation of catalase synthesis in Salmonella typhimurium. The specific activity of catalase in Salmonella typhimurium and other enteric bacteria decreased during the logarithmic phase of growth and increased at the onset and during the stationary phase. The increase in catalase synthesis at the end of the exponential phase in S. typhimurium cells coincided with the lowest pH value reached by the culture. Maintenance of the pH at a constant neutral value did not alter the typical pattern of synthesis in contradiction of the results previously reported (McCarthy and Hinshelwood. 1959). A sudden decrease in the pH value of an S. typhimurium culture during exponential growth by addition of HC1 did not cause an alteration in the catalase synthesis pattern. Addition of hydrogen peroxide to S. typhimurium cultures within the range 1 muM TO 2MM during the exponential growth phase stimulated catalase synthesis. The extent of catalase synthesis depended on the concentration of hydrogen peroxide; the maximum stimulation was observed at 80 muM. Increased catalase synthesis was not detected for 10 to 15 min after hydrogen peroxide addition. Hydrogen peroxide was produced by S. typhimurium cultures during the exponential and stationary growth phases. However, no direct relationship between hydrogen peroxide accumulation and synthesis of catalase was observed."}
{"id": "PMID:238956", "title": "Physical and chemical studies of Thiobacillus ferroxidans lipopolysaccharides.", "content": "The lipopolysaccharides (LPS) of the obligate acidophile Thiobacillus ferroxidans grown on iron, sulfur, and glucose as energy sources were examined for various physical and chemical properties. Both qualitative and quantitative variation were found among the three preparations. The LPS extracted from iron-grown cells (Fe-LPS) contained less than 3% protein compared to 18 to 25% in LPS extracted from either sulfur-grown cells (S-LPS) or glucose-grown cells (G-LPS). S-LPS showed two distinct sedimentable species, 61S and 9.3S, which could be fractionated on a column of Sepharose 4B. The relative densities of both S-LPS and G-LPS were found to be significantly greater than that of Fe-LPS. Spectral differences were noted when each LPS was reacted with a carbocyanine dye. Fe-LPS showed a single absorbance maximum at 472 nm, S-LPS displayed its maximum at 650 nm, and G-LPS showed two maxima, the first at 468 nm and the other at 655 nm. Analysis of the methyl ester derivatives of the LPS fatty aicds using gas chromatography-mass spectrometry revealed the presence of a very stable species, tentatively identified as a methoxy methyl ester with a formula of CH3-3-C10H10-COOCH3, as the major component from each LPS. beta-Hydroxymyristic acid was found only in Fe-LPS.", "contents": "Physical and chemical studies of Thiobacillus ferroxidans lipopolysaccharides. The lipopolysaccharides (LPS) of the obligate acidophile Thiobacillus ferroxidans grown on iron, sulfur, and glucose as energy sources were examined for various physical and chemical properties. Both qualitative and quantitative variation were found among the three preparations. The LPS extracted from iron-grown cells (Fe-LPS) contained less than 3% protein compared to 18 to 25% in LPS extracted from either sulfur-grown cells (S-LPS) or glucose-grown cells (G-LPS). S-LPS showed two distinct sedimentable species, 61S and 9.3S, which could be fractionated on a column of Sepharose 4B. The relative densities of both S-LPS and G-LPS were found to be significantly greater than that of Fe-LPS. Spectral differences were noted when each LPS was reacted with a carbocyanine dye. Fe-LPS showed a single absorbance maximum at 472 nm, S-LPS displayed its maximum at 650 nm, and G-LPS showed two maxima, the first at 468 nm and the other at 655 nm. Analysis of the methyl ester derivatives of the LPS fatty aicds using gas chromatography-mass spectrometry revealed the presence of a very stable species, tentatively identified as a methoxy methyl ester with a formula of CH3-3-C10H10-COOCH3, as the major component from each LPS. beta-Hydroxymyristic acid was found only in Fe-LPS."}
{"id": "PMID:238957", "title": "Purification and properties of malate dehydrogenase from Pseudomonas testosteroni.", "content": "Nicotinamide adenine dinucleotide-linked malate dehydrogenase has been purified from Pseudomonas testosteroni (ATCC 11996). The purification represents over 450-fold increase in specific activity. The amino acid composition of the enzyme was determined and found to be quite different from the composition of the malate dehydrogenases from animal sources as well as from Escherichia coli. Despite this difference, however, the data show that the enzymatic properties of the purified enzyme are remarkably similar to those of other malate dehydrogenases that have been previously studied. The Pseudomonas enzyme has a molecular weight of 74,000 and consists of two subunits of identical size. In addition to L-malate, the enzyme slowly oxidizes other four-carbon dicarboylates having an alpha-hydroxyl group of S configuration such as meso- and (-) tartrate. Rate-determining steps, which differ from that of the reaction involving L-malate, are discussed for the reaction involving these alternative substrates. Oxidation of hydroxymalonate, a process previously undetected with other malate dehydrogenases, is demonstrated fluorometrically. Hydroxymalonate and D-malate strongly enhance the fluorescence of the reduced nicotinamide adenine dinucleotide bound to the enzyme. The enzyme is A-stereospecific with respect to the coenzyme. Malate dehydrogenase is present in a single form in the Pseudomonas. The susceptibility of the enzyme to activation or inhibition by its substrates-particularly the favoring of the oxidation of malate at elevated concentrations-strongly resembles the properties of the mitochondrial enzymes. The present study reveals that whereas profound variations in chemical composition have occurred between the prokaryotic and eukaryotic enzymes, the physical and catalytic properties of malate dehydrogenase, unlike lactate dehydrogenase, are well conserved during the evolutionary process.", "contents": "Purification and properties of malate dehydrogenase from Pseudomonas testosteroni. Nicotinamide adenine dinucleotide-linked malate dehydrogenase has been purified from Pseudomonas testosteroni (ATCC 11996). The purification represents over 450-fold increase in specific activity. The amino acid composition of the enzyme was determined and found to be quite different from the composition of the malate dehydrogenases from animal sources as well as from Escherichia coli. Despite this difference, however, the data show that the enzymatic properties of the purified enzyme are remarkably similar to those of other malate dehydrogenases that have been previously studied. The Pseudomonas enzyme has a molecular weight of 74,000 and consists of two subunits of identical size. In addition to L-malate, the enzyme slowly oxidizes other four-carbon dicarboylates having an alpha-hydroxyl group of S configuration such as meso- and (-) tartrate. Rate-determining steps, which differ from that of the reaction involving L-malate, are discussed for the reaction involving these alternative substrates. Oxidation of hydroxymalonate, a process previously undetected with other malate dehydrogenases, is demonstrated fluorometrically. Hydroxymalonate and D-malate strongly enhance the fluorescence of the reduced nicotinamide adenine dinucleotide bound to the enzyme. The enzyme is A-stereospecific with respect to the coenzyme. Malate dehydrogenase is present in a single form in the Pseudomonas. The susceptibility of the enzyme to activation or inhibition by its substrates-particularly the favoring of the oxidation of malate at elevated concentrations-strongly resembles the properties of the mitochondrial enzymes. The present study reveals that whereas profound variations in chemical composition have occurred between the prokaryotic and eukaryotic enzymes, the physical and catalytic properties of malate dehydrogenase, unlike lactate dehydrogenase, are well conserved during the evolutionary process."}
{"id": "PMID:238958", "title": "Kinetics of recombination of heavy and light chains of a human IgG1 myeloma protein.", "content": "The recombination of alkylated H and L chains of a human myeloma protein (Jo) was studied by means of circular dichroism (CD). Marked CD changes were observed at 295 and 235 nm when H and L chains recombined. The change in the CD maximum at 235 nm was followed with time after mixing preparations of H and L chains in the pH range between 4 and 6. The recombination reaction was slow and followed second order kinetics. The observed rate constants were markedly dependent on pH. The pH dependence of the rate constant was analyzed assuming that there are two forms of H chain which are in a pH-dependent equilibrium with each other.", "contents": "Kinetics of recombination of heavy and light chains of a human IgG1 myeloma protein. The recombination of alkylated H and L chains of a human myeloma protein (Jo) was studied by means of circular dichroism (CD). Marked CD changes were observed at 295 and 235 nm when H and L chains recombined. The change in the CD maximum at 235 nm was followed with time after mixing preparations of H and L chains in the pH range between 4 and 6. The recombination reaction was slow and followed second order kinetics. The observed rate constants were markedly dependent on pH. The pH dependence of the rate constant was analyzed assuming that there are two forms of H chain which are in a pH-dependent equilibrium with each other."}
{"id": "PMID:238959", "title": "Partial purification, properties, and subcellulsr distribution of rat liver phosphatidate phosphatase.", "content": "Phosphatidate phosphatase (EC 3.1.3.4Y was purified 15- to 20-fold from the soluble fraction of rat liver. The purification procedure involved calcium phosphate gel adsorption and elution, ammonium sulfact precipitation, and molecular-sieve chromatography. For the enzyme assay, and aqueous dispersion of phosphatidate, rather than \"membrane-bound\" phosphatidate, was used as substrate. The partially purified enzyme depends almost entirely on the presence of Mg2+ for its activity. Morover, the activity of the enzyme is stimulated by phosphatidylcholine. The enzyme exhibits a high substrate specificity for phosphatidate. The apparent Km for phosphatidate is approximately 0.05 mM. The optimum pH is between 7.4 and 7.6. The enzyme is inhibited by fluoride and by p-chloromercuribenzoate. The subcellular distribution of phosphatidate phosphatase in rat liver was studied by assaying the activity of the enzyme in the presence of Mg2+ and phosphatidylcholine. In contrast ot the results of previous studies, most of the enzyme activity was found in the soluble fraction.", "contents": "Partial purification, properties, and subcellulsr distribution of rat liver phosphatidate phosphatase. Phosphatidate phosphatase (EC 3.1.3.4Y was purified 15- to 20-fold from the soluble fraction of rat liver. The purification procedure involved calcium phosphate gel adsorption and elution, ammonium sulfact precipitation, and molecular-sieve chromatography. For the enzyme assay, and aqueous dispersion of phosphatidate, rather than \"membrane-bound\" phosphatidate, was used as substrate. The partially purified enzyme depends almost entirely on the presence of Mg2+ for its activity. Morover, the activity of the enzyme is stimulated by phosphatidylcholine. The enzyme exhibits a high substrate specificity for phosphatidate. The apparent Km for phosphatidate is approximately 0.05 mM. The optimum pH is between 7.4 and 7.6. The enzyme is inhibited by fluoride and by p-chloromercuribenzoate. The subcellular distribution of phosphatidate phosphatase in rat liver was studied by assaying the activity of the enzyme in the presence of Mg2+ and phosphatidylcholine. In contrast ot the results of previous studies, most of the enzyme activity was found in the soluble fraction."}
{"id": "PMID:238960", "title": "Synthesis of polyglycerol phosphate by Bacillus stearothermophilus.", "content": "A particulate enzyme preparation from Bacillus stearothermophilus synthesized 1,3-poly(glycerol phosphage) from CDPglycerol at an optimum pH of 8.0 and the reaction was stimulated by divalent cations. Km for CDPglycerol was 0.18 mM. The synthesis was inhibited by CMP, CDP, and CTP and by concentrations of CDP-glycerol above 0.49 mM. The reaction was irreversible, The product had an average chain length of 8 glycerol units. About two thirds of the polymers were synthesized in entirety while the ramainder were attached to some acceptor by their phosphate end. The enzome was able to synthesize only a limited amount of polymer.", "contents": "Synthesis of polyglycerol phosphate by Bacillus stearothermophilus. A particulate enzyme preparation from Bacillus stearothermophilus synthesized 1,3-poly(glycerol phosphage) from CDPglycerol at an optimum pH of 8.0 and the reaction was stimulated by divalent cations. Km for CDPglycerol was 0.18 mM. The synthesis was inhibited by CMP, CDP, and CTP and by concentrations of CDP-glycerol above 0.49 mM. The reaction was irreversible, The product had an average chain length of 8 glycerol units. About two thirds of the polymers were synthesized in entirety while the ramainder were attached to some acceptor by their phosphate end. The enzome was able to synthesize only a limited amount of polymer."}
{"id": "PMID:238961", "title": "Mercuri-nitrophenol as a reporter group for the conformational change of hemoglobin.", "content": "One mole of horse hemoglobin tetramer reacts with 2 moles of 2-chloromercuri-4-nitrophenol (MNP) at beta 93 cysteine. The difference spectra between NMP-bound hemoglobin and hemoglobin, measured with the aid of ascorbic acid and ascorate oxidase [EC 1.10.3.3] as deoxygenation reagents, indicate that the pK of the phenolic hydroxyl group of MNP increases by 0.6 to 0.8 pH unit on deoxygenation of the hemoglobin. The Hill constant of the modified hemoglobin changes with pH. It decreases from about 2.4 at pH 6.8 to about 1.0 at pH 9.0 This effect of the reagent is interpreted as inherent to the reporter groups.", "contents": "Mercuri-nitrophenol as a reporter group for the conformational change of hemoglobin. One mole of horse hemoglobin tetramer reacts with 2 moles of 2-chloromercuri-4-nitrophenol (MNP) at beta 93 cysteine. The difference spectra between NMP-bound hemoglobin and hemoglobin, measured with the aid of ascorbic acid and ascorate oxidase [EC 1.10.3.3] as deoxygenation reagents, indicate that the pK of the phenolic hydroxyl group of MNP increases by 0.6 to 0.8 pH unit on deoxygenation of the hemoglobin. The Hill constant of the modified hemoglobin changes with pH. It decreases from about 2.4 at pH 6.8 to about 1.0 at pH 9.0 This effect of the reagent is interpreted as inherent to the reporter groups."}
{"id": "PMID:238962", "title": "A method for observing protein-protein interaction.", "content": "A method is proposed for observation of the interaction between charged macromolecules such as proteins. The method is based on the fact that the pK of an ionizable reporter group attached to a macromolecule can be altered by the electrostatic effect of another charged macromolecule which associates with the former. The effectiveness of the method was shown in the study of the association of bovine serum albumin with hen egg lysozyme [EC 3.2.1.17]. The  errors inherent in this method in obtaining the equilibrium constant of the association reaction and procedures for their correction are discussed.", "contents": "A method for observing protein-protein interaction. A method is proposed for observation of the interaction between charged macromolecules such as proteins. The method is based on the fact that the pK of an ionizable reporter group attached to a macromolecule can be altered by the electrostatic effect of another charged macromolecule which associates with the former. The effectiveness of the method was shown in the study of the association of bovine serum albumin with hen egg lysozyme [EC 3.2.1.17]. The  errors inherent in this method in obtaining the equilibrium constant of the association reaction and procedures for their correction are discussed."}
{"id": "PMID:238963", "title": "Purification of tubulin from bovine brain and its interaction with guanine nucleotides.", "content": "A rapid and sensitive assay for [3H]GTP binding activity of tubulin has been developed. This assay method is based on the quantitative retention of [3H]GTP. Tubulin complex on a nitrocellulose membrane filter. It was also found that bovine brain tubulin is markedly stablized by glycerol and GTP against denaturation. A large-scale purification of bovine brain tubulin was achieved using the new assay procedure and by the inclusion of glycerol and GTP in a buffer solution used for column chromatograph. The purified tubulin could be stored at -80degrees in the presence of glycerol and GTP for at least a year without any apprecialbe loss of [3H]GTP- and [3H]colchicine binding activities. The interaction of tubulin with guanine nucleotides was also studied using the nitorcellulose membrane filter procedure. It was found that the binding of [3H]GTP to tubulin with an empty exchangeable site proceeded promptly within k sec while the exchange of [3H]GTP- with a GTP-tubulin complex in which the exchangeable site had been occupied with unlabeled GTP occured more slowly. The dissociation constants for GTP and GDP at the exchangeable site of tubulin were determined as 0.5 times 10-6M and 1.9 times 10-6M, respectively. 5'-Guanylylimidodiphosphate could interact, although less strongly, with tubulin at this site, whereas the interaction of other nucleoside triphosphates includint ATP, CTP, UTP, and 5'-guanylyl methylenediphosphonate was very weak, if it occured at all. The presence of Mg2+ and a free sulfhydryl group was found to be essential for binding of [3H]GTP to tubulin. Ca2+ was found to replace Mg2+ in this binding reaction.", "contents": "Purification of tubulin from bovine brain and its interaction with guanine nucleotides. A rapid and sensitive assay for [3H]GTP binding activity of tubulin has been developed. This assay method is based on the quantitative retention of [3H]GTP. Tubulin complex on a nitrocellulose membrane filter. It was also found that bovine brain tubulin is markedly stablized by glycerol and GTP against denaturation. A large-scale purification of bovine brain tubulin was achieved using the new assay procedure and by the inclusion of glycerol and GTP in a buffer solution used for column chromatograph. The purified tubulin could be stored at -80degrees in the presence of glycerol and GTP for at least a year without any apprecialbe loss of [3H]GTP- and [3H]colchicine binding activities. The interaction of tubulin with guanine nucleotides was also studied using the nitorcellulose membrane filter procedure. It was found that the binding of [3H]GTP to tubulin with an empty exchangeable site proceeded promptly within k sec while the exchange of [3H]GTP- with a GTP-tubulin complex in which the exchangeable site had been occupied with unlabeled GTP occured more slowly. The dissociation constants for GTP and GDP at the exchangeable site of tubulin were determined as 0.5 times 10-6M and 1.9 times 10-6M, respectively. 5'-Guanylylimidodiphosphate could interact, although less strongly, with tubulin at this site, whereas the interaction of other nucleoside triphosphates includint ATP, CTP, UTP, and 5'-guanylyl methylenediphosphonate was very weak, if it occured at all. The presence of Mg2+ and a free sulfhydryl group was found to be essential for binding of [3H]GTP to tubulin. Ca2+ was found to replace Mg2+ in this binding reaction."}
{"id": "PMID:238964", "title": "Analysis of regulatory factors for urea synthesis by isolated perfused rat liver. I. Urea synthesis with ammonia and glutamine as nitrogen sources.", "content": "Urea synthesis was  studied using the isolated liver perfusion with ammonium cholride and glutamine as nitrogen sources. The rate of urea formation increases with ammonium cholorde concentration up to 5mM, and the rate remained constant in the range between 5 and 20mM of ammonium chloride as the substrate. The concentration of ammonia in the medium to support the half-maximum velocity of urea formation was 0.7mM. The rate of urea formation was stimulated by the addition of 2.5mM ornithine, and the greater part of the ornithine which was taken up into the liver was accumulated as citrulline in the presence of ammonia. A considerable accelerating effect of N-acetylglutamate on the synthetic rate was observed, but a rather high concentration  of N-acetylglutamate was required in order to obtain the maximum effect possibly, because its permeability into liver cells may be limited. A marked additive effect on the rate of urea formation was observed with the combined addition of ornithine and N-acetylglutamate. The metabolic conversion of glutamine nitrogen to urea in the perfused rat liver and the effect of several compounds which stimulated urea synthesis with ammonia were further examined. The process of conversion of glutamine nitrogen to urea might be composed of the following three steps. In the first lag phase, a small amount of glutamine was removed from the medium. In the second stage, the glutamine level decreased rapidly and ammonia was accumulated in the perfusate. The third stage was a period in which glutamine concentration remained at a constant low level, and the accumulated ammonia was rapidly conversed to urea. The rate of urea formation in this third stage was found to be much higher than that with ammonia as the substrate. The maximum rate of glutamine removal was obtained at pH 7.7 of the perfusate and at a concentration of 10mM glutamine. Urea formation with glutamine was also stimulated by the addition of ornithine, malate, or N-acetylglutamate, which had accelerating effects on the urea synthesis with ammonia. This stimulation was due to an effective conversion of ammonia to urea, but no change in the rate of removal glutamine was obtained.", "contents": "Analysis of regulatory factors for urea synthesis by isolated perfused rat liver. I. Urea synthesis with ammonia and glutamine as nitrogen sources. Urea synthesis was  studied using the isolated liver perfusion with ammonium cholride and glutamine as nitrogen sources. The rate of urea formation increases with ammonium cholorde concentration up to 5mM, and the rate remained constant in the range between 5 and 20mM of ammonium chloride as the substrate. The concentration of ammonia in the medium to support the half-maximum velocity of urea formation was 0.7mM. The rate of urea formation was stimulated by the addition of 2.5mM ornithine, and the greater part of the ornithine which was taken up into the liver was accumulated as citrulline in the presence of ammonia. A considerable accelerating effect of N-acetylglutamate on the synthetic rate was observed, but a rather high concentration  of N-acetylglutamate was required in order to obtain the maximum effect possibly, because its permeability into liver cells may be limited. A marked additive effect on the rate of urea formation was observed with the combined addition of ornithine and N-acetylglutamate. The metabolic conversion of glutamine nitrogen to urea in the perfused rat liver and the effect of several compounds which stimulated urea synthesis with ammonia were further examined. The process of conversion of glutamine nitrogen to urea might be composed of the following three steps. In the first lag phase, a small amount of glutamine was removed from the medium. In the second stage, the glutamine level decreased rapidly and ammonia was accumulated in the perfusate. The third stage was a period in which glutamine concentration remained at a constant low level, and the accumulated ammonia was rapidly conversed to urea. The rate of urea formation in this third stage was found to be much higher than that with ammonia as the substrate. The maximum rate of glutamine removal was obtained at pH 7.7 of the perfusate and at a concentration of 10mM glutamine. Urea formation with glutamine was also stimulated by the addition of ornithine, malate, or N-acetylglutamate, which had accelerating effects on the urea synthesis with ammonia. This stimulation was due to an effective conversion of ammonia to urea, but no change in the rate of removal glutamine was obtained."}
{"id": "PMID:238965", "title": "Purification and some properties of cathepsin A of small molecular size from pig kidney.", "content": "Cathepsin A [EC 3.4.2.-] of small molecular size (cathepsin A, S) has been purified about 800-fold from pig kidney by procedures including chromatographies on DEAE-Sephadex, SP-Sephadex, and Sephadex G-150. 1. The homogeneity of the purified enzyme was proved by ultracentrifugation and polyacrylamide gel electrophoresis. The molecular weight (100,000) and isoelectric point (pI=5.0) were estimated. 2. The enzyme was remarkably stabilized by sucrose and KCl, and was most stable at pH 5-5.5 in the presence of both stabilizers. The enzyme had not only peptidase activity but also esterase and amidase activity; it was optimally active at pH 5.2 for peptide hydrolysis and at pH 8 for the hydrolysis of esters and amides. 3. Diisopropyl fluorophosphate and iodoacetamide completely inhibited these three activities. 4. The enzyme hydrolyzed various benzoyl- and benzyloxycarbonyl-dipeptides with neutral, acidic, and basic amino acids, and proline in the C-terminal position. The carboxypeptidase nature of the enzyme was proved by its action on an oligopeptide. 5. Several enzymatic properties of cathepsin A, S were almost the same as thoas of cathepsin A of large molecular size (cathepsin A, L) and the crude homogenate.", "contents": "Purification and some properties of cathepsin A of small molecular size from pig kidney. Cathepsin A [EC 3.4.2.-] of small molecular size (cathepsin A, S) has been purified about 800-fold from pig kidney by procedures including chromatographies on DEAE-Sephadex, SP-Sephadex, and Sephadex G-150. 1. The homogeneity of the purified enzyme was proved by ultracentrifugation and polyacrylamide gel electrophoresis. The molecular weight (100,000) and isoelectric point (pI=5.0) were estimated. 2. The enzyme was remarkably stabilized by sucrose and KCl, and was most stable at pH 5-5.5 in the presence of both stabilizers. The enzyme had not only peptidase activity but also esterase and amidase activity; it was optimally active at pH 5.2 for peptide hydrolysis and at pH 8 for the hydrolysis of esters and amides. 3. Diisopropyl fluorophosphate and iodoacetamide completely inhibited these three activities. 4. The enzyme hydrolyzed various benzoyl- and benzyloxycarbonyl-dipeptides with neutral, acidic, and basic amino acids, and proline in the C-terminal position. The carboxypeptidase nature of the enzyme was proved by its action on an oligopeptide. 5. Several enzymatic properties of cathepsin A, S were almost the same as thoas of cathepsin A of large molecular size (cathepsin A, L) and the crude homogenate."}
{"id": "PMID:238966", "title": "Affinity chromatography of alpha-chymotrypsin, subtilism, and metalloendopeptidases on carbobenzoxy-L-phenylalanyl-triehtylenetetraminyl-sepharose.", "content": "Carbobenzoxy-L-phenylalanyl-triethylenetetraminyl-Sepharose (Z-L-Phe-T-Sepharose) was found to be an effective affinity adsorbent for bovine pancreatic alpha-chymotrypsin [EC 3.4.21.1] as well as neutral [EC 3.4.24.4] and alkaline [EC 3.4.21.14] proteases of Bacillus species. These enzymes were adsorbed in the neutral pH range. alpha-Chymotrypsin was recovered by elution with 0.1 A acetic acid while neutral subtilopeptidase was eluted with 0.5 M NaCl at pH 0. Thermolysin and subtilisin were found in eluates with 1.5 and 2.0 M guanidine-HCl at pH 7.2, respectively. The resulting enzymes appeared homogeneous on disc-electrophoresis and showed higher specific activities than those of crystalline or highly purified preparations available commercially. Modifications of the active site serines of alpha-chymotrypsin and subtilisin by treatment with diisopropylfluorophosphate (DFP) or phenylmethanesulfonyl fluoride (PMSF) resulted in loss in their binding abilities to the adsorbent. Complexes of porcine alpha2-macroglobulin with each of these four enzymes and that of Streptomyces-subtilisin inhibitor (S-SI) with subtilisin were also found in nonadsorbed fractions.", "contents": "Affinity chromatography of alpha-chymotrypsin, subtilism, and metalloendopeptidases on carbobenzoxy-L-phenylalanyl-triehtylenetetraminyl-sepharose. Carbobenzoxy-L-phenylalanyl-triethylenetetraminyl-Sepharose (Z-L-Phe-T-Sepharose) was found to be an effective affinity adsorbent for bovine pancreatic alpha-chymotrypsin [EC 3.4.21.1] as well as neutral [EC 3.4.24.4] and alkaline [EC 3.4.21.14] proteases of Bacillus species. These enzymes were adsorbed in the neutral pH range. alpha-Chymotrypsin was recovered by elution with 0.1 A acetic acid while neutral subtilopeptidase was eluted with 0.5 M NaCl at pH 0. Thermolysin and subtilisin were found in eluates with 1.5 and 2.0 M guanidine-HCl at pH 7.2, respectively. The resulting enzymes appeared homogeneous on disc-electrophoresis and showed higher specific activities than those of crystalline or highly purified preparations available commercially. Modifications of the active site serines of alpha-chymotrypsin and subtilisin by treatment with diisopropylfluorophosphate (DFP) or phenylmethanesulfonyl fluoride (PMSF) resulted in loss in their binding abilities to the adsorbent. Complexes of porcine alpha2-macroglobulin with each of these four enzymes and that of Streptomyces-subtilisin inhibitor (S-SI) with subtilisin were also found in nonadsorbed fractions."}
{"id": "PMID:238967", "title": "Ethoxyformylation of ribonuclease U2 form Ustilago sphaerogena.", "content": "RNase U2 was inactivated by incubation with ethoxyformic anhydride at pH 6.0 and pH 4.5.  The absorbance of the RNase U2 increased at around 250 nm and decreased at around 280 nm.  The inactivation occurred in parallel with the amount of modified histidine and plots of the relationship between the remaining activity and the modified histidine suggested that the modification of one of the two histidine residues totally inactivated the enzyme.  The inactivated enzyme RNase U2 was reactivated by a low concentration of hydroxyamine, with removal of the ethoxyformyl group from the modified histidine residue.  At pH 4.5, 2'-adenylate and 2'-guanylate protected RNase U2 from inactivation by ethoxyformic anhydride.  The difference CD spectra showed that the ability of RNase U2 to form a complex with 2'-adenylate was lost on ethoxyformylation.", "contents": "Ethoxyformylation of ribonuclease U2 form Ustilago sphaerogena. RNase U2 was inactivated by incubation with ethoxyformic anhydride at pH 6.0 and pH 4.5.  The absorbance of the RNase U2 increased at around 250 nm and decreased at around 280 nm.  The inactivation occurred in parallel with the amount of modified histidine and plots of the relationship between the remaining activity and the modified histidine suggested that the modification of one of the two histidine residues totally inactivated the enzyme.  The inactivated enzyme RNase U2 was reactivated by a low concentration of hydroxyamine, with removal of the ethoxyformyl group from the modified histidine residue.  At pH 4.5, 2'-adenylate and 2'-guanylate protected RNase U2 from inactivation by ethoxyformic anhydride.  The difference CD spectra showed that the ability of RNase U2 to form a complex with 2'-adenylate was lost on ethoxyformylation."}
{"id": "PMID:238968", "title": "Inhibition of urease activity by hydroxamic acid derivatives of amino acids.", "content": "Hydroxamic acids have been reported to be potent and specific inhibitors of urease (EC 3.5.1.5) activity of plant and bacterial origin.  The present investigation was performed on the inhibitory effect of hydroxamic acid derivatives of naturally occurring amino acids on the urease activity of the Jack Bean and the alimentary tracts of rats.  Methionine-hydroxamic acid was the most powerful inhibitor (I50=3.9 X 10(-6) M) among nineteen alpha-aminoacyl hydroxamic acids.  Phenylalanine-, serine-, alanine-, glycine-, histidine-, threonine-, leucine-, and arginine-hydroxamic acids followed, in order of decreasing inhibitory power.  The inhibition proceeded with time at a comparable rate to fatty acyl hydroxamic acid inhibition.  The I50 values of alpha-aminoacyl hydroxamic acids were found to be almost equal to those of the corresponding fatty acyl hydroxamic acids.  This fact shows that the alpha-amino group did not affect inhibitory power.  However, aspartic-beta-, lysine-, and glutamic-gamma-hydroxamic acids, in descending order, were much less inhibitory, probably due to the presence of a carboxyl or omega-amino group.  Furthermore, the pH optimum of the inhibition shifted to lower pH in the presence of a carboxyl group, and to a higher pH in  e presence of an amino group.  The results suggest that the dissociation of an acidic or a basic group reduces the inhibitory power of hydroxamic acid.  Hydroxamic acid inhibits urease activity with strict specificity, excpet for aspartic-beta-hydroxamic acid, which inhibited asparaginase competitively.  Hydroxamic acid derivatives of amino acids inhibited not only the urease activity of the Jack Bean, but also that of the caecum and ileum parts of the rat intestine.", "contents": "Inhibition of urease activity by hydroxamic acid derivatives of amino acids. Hydroxamic acids have been reported to be potent and specific inhibitors of urease (EC 3.5.1.5) activity of plant and bacterial origin.  The present investigation was performed on the inhibitory effect of hydroxamic acid derivatives of naturally occurring amino acids on the urease activity of the Jack Bean and the alimentary tracts of rats.  Methionine-hydroxamic acid was the most powerful inhibitor (I50=3.9 X 10(-6) M) among nineteen alpha-aminoacyl hydroxamic acids.  Phenylalanine-, serine-, alanine-, glycine-, histidine-, threonine-, leucine-, and arginine-hydroxamic acids followed, in order of decreasing inhibitory power.  The inhibition proceeded with time at a comparable rate to fatty acyl hydroxamic acid inhibition.  The I50 values of alpha-aminoacyl hydroxamic acids were found to be almost equal to those of the corresponding fatty acyl hydroxamic acids.  This fact shows that the alpha-amino group did not affect inhibitory power.  However, aspartic-beta-, lysine-, and glutamic-gamma-hydroxamic acids, in descending order, were much less inhibitory, probably due to the presence of a carboxyl or omega-amino group.  Furthermore, the pH optimum of the inhibition shifted to lower pH in the presence of a carboxyl group, and to a higher pH in  e presence of an amino group.  The results suggest that the dissociation of an acidic or a basic group reduces the inhibitory power of hydroxamic acid.  Hydroxamic acid inhibits urease activity with strict specificity, excpet for aspartic-beta-hydroxamic acid, which inhibited asparaginase competitively.  Hydroxamic acid derivatives of amino acids inhibited not only the urease activity of the Jack Bean, but also that of the caecum and ileum parts of the rat intestine."}
{"id": "PMID:238969", "title": "Comparison between muscle and liver enolases and their behavior during differentiation and growth.", "content": "1. Rabbit liver enolase (EC 4.2.1.11) was purified about 200-fold and the enzyme was distinguished from crystalline muscle enolase by column isoelectrofocusing.  It was found that the pI of muscle enolase was at about pH 8.8 and the pI of liver enolase was at about pH 6.7.  Liver enolase was more liable to heat than muscle enolase.  Anti-muscle enolase antibody did not react with liver enolase in double diffusion and immunoprecipitation tests.  No substantial  difference seemed to exist between muscle and liver enolases in pH optima, kinetic constants, and gel filtration. 2. It was observed by electrofocusing that the pI of rat muscle enolase was pH 7.2 to 7.9 and that of liver enolase was about pH 5.9.  The main component of muscle enolase was designated as type A enolase, and liver enolase as type B enolase.  Type A enolase was present in skeletal muscle and heart muscle.  Type B enolase was widely distributed and present in liver, kidney, spleen, brain, lung, small intestine, and heart muscle.  More acidic isozyme than type B enolase coexisted in the brain, and more basic isozyme than type A enolase, coexisted in the small intestine.  A prototype of enolase in the early stage of differentiation was found to be type B enolase and, as differentiation progressed, type B decreased in muscle, while type A increased.  On the other hand, liver enolase was retained as type B during differentiation.  The enolase in regenerating liver was the same as in normal liver.", "contents": "Comparison between muscle and liver enolases and their behavior during differentiation and growth. 1. Rabbit liver enolase (EC 4.2.1.11) was purified about 200-fold and the enzyme was distinguished from crystalline muscle enolase by column isoelectrofocusing.  It was found that the pI of muscle enolase was at about pH 8.8 and the pI of liver enolase was at about pH 6.7.  Liver enolase was more liable to heat than muscle enolase.  Anti-muscle enolase antibody did not react with liver enolase in double diffusion and immunoprecipitation tests.  No substantial  difference seemed to exist between muscle and liver enolases in pH optima, kinetic constants, and gel filtration. 2. It was observed by electrofocusing that the pI of rat muscle enolase was pH 7.2 to 7.9 and that of liver enolase was about pH 5.9.  The main component of muscle enolase was designated as type A enolase, and liver enolase as type B enolase.  Type A enolase was present in skeletal muscle and heart muscle.  Type B enolase was widely distributed and present in liver, kidney, spleen, brain, lung, small intestine, and heart muscle.  More acidic isozyme than type B enolase coexisted in the brain, and more basic isozyme than type A enolase, coexisted in the small intestine.  A prototype of enolase in the early stage of differentiation was found to be type B enolase and, as differentiation progressed, type B decreased in muscle, while type A increased.  On the other hand, liver enolase was retained as type B during differentiation.  The enolase in regenerating liver was the same as in normal liver."}
{"id": "PMID:238970", "title": "Temperature-jump studies on benzeneboronic acid-serine protease interactions.  Subtilisin and alpha-chymotrypsin.", "content": "The interactions of benzeneboronic acid (BBA) as a transition state analog with subtilisin (EC 3.4.21.4) and with alpha-chymotrypsin (EC 3.4.21.1) were investigated kinetically by the temperature-jump method using pH indicators.  For both enzymes, the concentration dependence of the relaxation time was consistent with a two-step mechanism involving a fast bimolecular association followed by a slow, unimolecular process.  The possibility of a trigonal-tetrahedral interconversion of BBA at the active site of the enzyme is discussed.", "contents": "Temperature-jump studies on benzeneboronic acid-serine protease interactions.  Subtilisin and alpha-chymotrypsin. The interactions of benzeneboronic acid (BBA) as a transition state analog with subtilisin (EC 3.4.21.4) and with alpha-chymotrypsin (EC 3.4.21.1) were investigated kinetically by the temperature-jump method using pH indicators.  For both enzymes, the concentration dependence of the relaxation time was consistent with a two-step mechanism involving a fast bimolecular association followed by a slow, unimolecular process.  The possibility of a trigonal-tetrahedral interconversion of BBA at the active site of the enzyme is discussed."}
{"id": "PMID:238971", "title": "Extradiol cleavage of 3-substituted catechols by an intradiol dioxygenase, pyrocatechase, from a Pseudomonad.", "content": "Pyrocatechase (catechol 1,2-oxidoreductase (decyclizing), EC 1.13.11.1), a ferric ion-containing dioxygenase from Pseudomonas arvilla C-1, catalyzes the intradiol cleavage of catechol with insertion of 2 atoms of molecular oxygen to form cis,cis-muconic acid. The enzyme also catalyzed the oxidation of various catechol derivatives, including 4-methylcatechol, 4-chlorocatechol, 4-formylcatechol (protocatechualdehyde), 4,5-dichlorocatechol, 3,5-dichlorocatechol, 3-methylcatechol, 3-methoxycatechol, and 3-hydroxycatechol (pyrogallol). All of these substrates gave products having an absorption maximum at around 260 nm, which is characteristic of cis,cis-muconic acid derivatives. However, when 3-methylcatechol was used as substrate, the product formed showed two absorption maxima at 390 and 260 nm. These two absorption maxima were found to be attributable to two different products, 2-hydroxy-6-oxo-2,4-heptadienoic acid and 5-carboxy-2-methyl-2,4-pentadienoic acid (2-methylmuconic acid). The former was produced by the extradiol cleavage between the carbon atom carrying the hydroxyl group and the carbon atom carrying the hydroxyl group and the carbon atom carrying the methyl group; the latter by an intradiol cleavage between two hydroxyl groups. Since these products were unstable, they were converted to and identified as 6-methylpyridine-2-carboxylic acid and 2-methylmuconic acid dimethylester, respectively. Similarly, 3-methoxycatechol gave two products, namely, 2-hydroxy-5-methoxycarbonyl-2,4-pentadienoic acid and 5-carboxy-2-methoxy-2,4-pentadienoic acid (2-methoxymuconic acid). With 3-methylcatechol as substrate, the ratio of intradiol and extradiol cleavage activities of Pseudomonas pyrocatechase during purification was almost constant and was about 17. The final preparation of the enzyme was homogeneous when examined by disc gel electrophoresis and catalyzed both reactions simultaneously with the same ratio as during purification. All attempts to resolve the enzyme into two components with separate activities, including inactivation of the enzyme with urea or heat, treatment with sulfhydryl-blocking reagents or chelating agents, and inhibition of the enzyme with various inhibitors, proved unsuccessful. These results strongly suggest that Pseudomonas pyrocatechase is a single enzyme, which catalyzes simultaneously both intradiol and extradiol cleavages of some 3-substituted catechols.", "contents": "Extradiol cleavage of 3-substituted catechols by an intradiol dioxygenase, pyrocatechase, from a Pseudomonad. Pyrocatechase (catechol 1,2-oxidoreductase (decyclizing), EC 1.13.11.1), a ferric ion-containing dioxygenase from Pseudomonas arvilla C-1, catalyzes the intradiol cleavage of catechol with insertion of 2 atoms of molecular oxygen to form cis,cis-muconic acid. The enzyme also catalyzed the oxidation of various catechol derivatives, including 4-methylcatechol, 4-chlorocatechol, 4-formylcatechol (protocatechualdehyde), 4,5-dichlorocatechol, 3,5-dichlorocatechol, 3-methylcatechol, 3-methoxycatechol, and 3-hydroxycatechol (pyrogallol). All of these substrates gave products having an absorption maximum at around 260 nm, which is characteristic of cis,cis-muconic acid derivatives. However, when 3-methylcatechol was used as substrate, the product formed showed two absorption maxima at 390 and 260 nm. These two absorption maxima were found to be attributable to two different products, 2-hydroxy-6-oxo-2,4-heptadienoic acid and 5-carboxy-2-methyl-2,4-pentadienoic acid (2-methylmuconic acid). The former was produced by the extradiol cleavage between the carbon atom carrying the hydroxyl group and the carbon atom carrying the hydroxyl group and the carbon atom carrying the methyl group; the latter by an intradiol cleavage between two hydroxyl groups. Since these products were unstable, they were converted to and identified as 6-methylpyridine-2-carboxylic acid and 2-methylmuconic acid dimethylester, respectively. Similarly, 3-methoxycatechol gave two products, namely, 2-hydroxy-5-methoxycarbonyl-2,4-pentadienoic acid and 5-carboxy-2-methoxy-2,4-pentadienoic acid (2-methoxymuconic acid). With 3-methylcatechol as substrate, the ratio of intradiol and extradiol cleavage activities of Pseudomonas pyrocatechase during purification was almost constant and was about 17. The final preparation of the enzyme was homogeneous when examined by disc gel electrophoresis and catalyzed both reactions simultaneously with the same ratio as during purification. All attempts to resolve the enzyme into two components with separate activities, including inactivation of the enzyme with urea or heat, treatment with sulfhydryl-blocking reagents or chelating agents, and inhibition of the enzyme with various inhibitors, proved unsuccessful. These results strongly suggest that Pseudomonas pyrocatechase is a single enzyme, which catalyzes simultaneously both intradiol and extradiol cleavages of some 3-substituted catechols."}
{"id": "PMID:238972", "title": "Identification of adenylate cyclase-coupled beta-adrenergic receptors in frog erythrocytes with (minus)-[3-H] alprenolol.", "content": "(minus)-Alprenolol, a potent, competitive beta-adrenergic antagonist labeled to high specific activity with tritium (17 Ci per mmol), has been used to identify binding sites in frog erythrocyte membranes having many of the characteristics to be expected of the beta-adrenergic receptors which are linked to adenylate cyclase in these membranes. The chromatographic behavior and biological activity of the labeled and native drug were essentially identical. (minus)-Alprenolol and (minus)-[3-H]alprenolol both competitively antagonize isoproterenol stimulation of frog erythrocyte membrane adenylate cyclase with a KD OF 5 TO 10 NM. (minus)-[3-H]Alprenolol binding to sites in the frog erythrocyte membranes was studied by a centrifugal assay. At 37 degrees, equilibrium binding was established within 5 min and the half-time for dissociation of bound (minus)-[3-H]alprenolol was approximately 30 s. This rapid onset and dissociation of (minus)-[3-H]alprenolol binding was in good agreement with the rapid onset of action of beta-adrenergic agonists and antagonists on the frog erythrocyte adenylate cyclase. (minus)-[3-H]Alprenolol binding was saturable. There were 0.25 to 0.35 pmol of (minus)-[3-H]alprenolol binding sites per mg of protein corresponding to 1300 to 1800 binding sites per intact frog erythrocyte. The binding sites showed half-maximal saturation at 5.0 to 10 nM (minus)-[3-H]alprenolol, which is in good agreement with the KD for alprenolol antagonism of isoproterenol stimulation of adenylate cyclase. The (minus)-[3-H]alprenolol binding sites exhibited strict stereospecificity. (minus)-Stereoisomers of beta-adrenergic antagonists or agonists were approximately 2 orders of magnitude more potent than the (+)-stereoisomers in competing for the binding sites. Comparable stereospecificity was apparent when agonists and antagonists were tested for their ability to interact with the adenylate cyclase-coupled beta-adrenergic receptors in the membranes. Potency series of 11 agonists and 13 antagonists for inhibition of binding and interaction with adenylate cyclase were identical and were characteristic of a beta2-adrenergic receptor. A variety of nonphysiologically active compounds containing a catechol moiety as well as several metabolites and cholinergic agents did not inhibit (minus)-[3-H]alprenolol binding or interact significantly as agonists or antagonists with the adenylate cyclase. The (minus)-[3-H]alprenolol binding sites studied appear to be equivalent to the beta-adrenergic receptor binding sites in the frog erythrocyte membranes.", "contents": "Identification of adenylate cyclase-coupled beta-adrenergic receptors in frog erythrocytes with (minus)-[3-H] alprenolol. (minus)-Alprenolol, a potent, competitive beta-adrenergic antagonist labeled to high specific activity with tritium (17 Ci per mmol), has been used to identify binding sites in frog erythrocyte membranes having many of the characteristics to be expected of the beta-adrenergic receptors which are linked to adenylate cyclase in these membranes. The chromatographic behavior and biological activity of the labeled and native drug were essentially identical. (minus)-Alprenolol and (minus)-[3-H]alprenolol both competitively antagonize isoproterenol stimulation of frog erythrocyte membrane adenylate cyclase with a KD OF 5 TO 10 NM. (minus)-[3-H]Alprenolol binding to sites in the frog erythrocyte membranes was studied by a centrifugal assay. At 37 degrees, equilibrium binding was established within 5 min and the half-time for dissociation of bound (minus)-[3-H]alprenolol was approximately 30 s. This rapid onset and dissociation of (minus)-[3-H]alprenolol binding was in good agreement with the rapid onset of action of beta-adrenergic agonists and antagonists on the frog erythrocyte adenylate cyclase. (minus)-[3-H]Alprenolol binding was saturable. There were 0.25 to 0.35 pmol of (minus)-[3-H]alprenolol binding sites per mg of protein corresponding to 1300 to 1800 binding sites per intact frog erythrocyte. The binding sites showed half-maximal saturation at 5.0 to 10 nM (minus)-[3-H]alprenolol, which is in good agreement with the KD for alprenolol antagonism of isoproterenol stimulation of adenylate cyclase. The (minus)-[3-H]alprenolol binding sites exhibited strict stereospecificity. (minus)-Stereoisomers of beta-adrenergic antagonists or agonists were approximately 2 orders of magnitude more potent than the (+)-stereoisomers in competing for the binding sites. Comparable stereospecificity was apparent when agonists and antagonists were tested for their ability to interact with the adenylate cyclase-coupled beta-adrenergic receptors in the membranes. Potency series of 11 agonists and 13 antagonists for inhibition of binding and interaction with adenylate cyclase were identical and were characteristic of a beta2-adrenergic receptor. A variety of nonphysiologically active compounds containing a catechol moiety as well as several metabolites and cholinergic agents did not inhibit (minus)-[3-H]alprenolol binding or interact significantly as agonists or antagonists with the adenylate cyclase. The (minus)-[3-H]alprenolol binding sites studied appear to be equivalent to the beta-adrenergic receptor binding sites in the frog erythrocyte membranes."}
{"id": "PMID:238973", "title": "The formation of hydrogen peroxide during the oxidation of reduced nicotinamide adenine dinucleotide by cytochrome o from Vitreoscilla.", "content": "The formation of hydrogen peroxide during the oxidation of NADH by purified preparations of cytochrome o has been demonstrated by employing three independent methods: polarographic, colorimetric, and fluorometric. The first two methods were used to assay for the accumulation of hydrogen peroxide and showed that hydrogen peroxide did accumulate as a product, but only about 30% of the oxygen consumed or 15 to 20% of the NADH oxidized was recoverable as hydrogen peroxide. This lack of 1:1 stoichiometry was not due to residual catalase activity in these preparations which could be eliminated by freeze-thawing. Thus, hydrogen peroxide may not be the sole or primary product of the NADH-cytochrome o oxidase reaction. The fluorometric assay could be coupled directly to the NADH-cytochrome o oxidase reaction in one medium, and this method showed that hydrogen peroxide was generated continuously from the beginning of the reaction in a 1:1 stoichiometry, hydrogen peroxide generated to NADH oxidized. This result suggests that hydrogen peroxide is an intermediate that can be trapped efficiently under the conditions of the fluorometric assay, whereas under the conditions of the first two assays most of the hydrogen peroxide generated undergoes further reaction. Exogenously added FAD or FMN increased the percentage of hydrogen peroxide that accumulated in the NADHcytochrome o oxidase reaction. Flavin is believed to act on the reductase side of cytochrome o so the increased percentage of hydrogen peroxide is not likely to result from the direct reaction of reduced flavin with oxygen.", "contents": "The formation of hydrogen peroxide during the oxidation of reduced nicotinamide adenine dinucleotide by cytochrome o from Vitreoscilla. The formation of hydrogen peroxide during the oxidation of NADH by purified preparations of cytochrome o has been demonstrated by employing three independent methods: polarographic, colorimetric, and fluorometric. The first two methods were used to assay for the accumulation of hydrogen peroxide and showed that hydrogen peroxide did accumulate as a product, but only about 30% of the oxygen consumed or 15 to 20% of the NADH oxidized was recoverable as hydrogen peroxide. This lack of 1:1 stoichiometry was not due to residual catalase activity in these preparations which could be eliminated by freeze-thawing. Thus, hydrogen peroxide may not be the sole or primary product of the NADH-cytochrome o oxidase reaction. The fluorometric assay could be coupled directly to the NADH-cytochrome o oxidase reaction in one medium, and this method showed that hydrogen peroxide was generated continuously from the beginning of the reaction in a 1:1 stoichiometry, hydrogen peroxide generated to NADH oxidized. This result suggests that hydrogen peroxide is an intermediate that can be trapped efficiently under the conditions of the fluorometric assay, whereas under the conditions of the first two assays most of the hydrogen peroxide generated undergoes further reaction. Exogenously added FAD or FMN increased the percentage of hydrogen peroxide that accumulated in the NADHcytochrome o oxidase reaction. Flavin is believed to act on the reductase side of cytochrome o so the increased percentage of hydrogen peroxide is not likely to result from the direct reaction of reduced flavin with oxygen."}
{"id": "PMID:238974", "title": "Guinea pig liver 3-hydroxyhexobarbital dehydrogenase. Purification and properties.", "content": "3-Hydroxyhexobarbital dehydrogenase, which catalyzes the reversible oxidation of 3-hydroxyhexobarbital to 3-oxohexobarbital, has been purified 470-fold from the soluble fraction of guinea pig liver with a yield of 47%. The specific activity of the purified enzyme is 9.4 units/mg of protein. Results of polyacrylamide gel disc electrophoresis and isoelectric focusing indicated that the purified enzyme preparation is a single and homogeneous protein. NADP+ served as preferred co-factor, but NAD+ is also utilized in the presence of phosphate ion. The guinea pig liver enzyme possessed a relatively narrow substrate specificity in comparison with the rabbit liver enzyme. It is very distinctive that guinea pig liver 3-hydroxyhexobarbital dehydrogenase catalyzes the dehydrogenation of 17beta-hydroxysteroids such as testosterone, 4-androstene-3beta,17beta-diol, 5alpha-androstane-3alpha,17beta-diol, 5alpha-androstane-3beta,17beta-diol, 5alpha-androstan-17beta-ol-3-one, and 5beta-androstane-3alpha,17beta-diol.", "contents": "Guinea pig liver 3-hydroxyhexobarbital dehydrogenase. Purification and properties. 3-Hydroxyhexobarbital dehydrogenase, which catalyzes the reversible oxidation of 3-hydroxyhexobarbital to 3-oxohexobarbital, has been purified 470-fold from the soluble fraction of guinea pig liver with a yield of 47%. The specific activity of the purified enzyme is 9.4 units/mg of protein. Results of polyacrylamide gel disc electrophoresis and isoelectric focusing indicated that the purified enzyme preparation is a single and homogeneous protein. NADP+ served as preferred co-factor, but NAD+ is also utilized in the presence of phosphate ion. The guinea pig liver enzyme possessed a relatively narrow substrate specificity in comparison with the rabbit liver enzyme. It is very distinctive that guinea pig liver 3-hydroxyhexobarbital dehydrogenase catalyzes the dehydrogenation of 17beta-hydroxysteroids such as testosterone, 4-androstene-3beta,17beta-diol, 5alpha-androstane-3alpha,17beta-diol, 5alpha-androstane-3beta,17beta-diol, 5alpha-androstan-17beta-ol-3-one, and 5beta-androstane-3alpha,17beta-diol."}
{"id": "PMID:238975", "title": "Molecular interactions of adenosine triphosphatase with the mitochondrial membrane as revealed by a spin label study.", "content": "Mitochondrial ATPase complex has been spin-labeled in the membrane using the inhibitor N-(2,2,6,6-tetramethylpeperidyl-1-OXYL)-N(cyclohexyl)carbodiimide (nccd). the amount of NCCD bound to mitochondrial fragments is 0.5 nmol/mg and cannot be dialyzed or extracted with ether, chloroform, or methanol. The electron paramagnetic resonance spectrum of NCCD bound to fragments is pH-sensitive, a greater label immobilization occurring at pH values lower or higher than 7. Ether extraction removes the ATPase inhibition by NCCD without detaching the label. This effect appears to be the consequence of the dislocation of some components of the ATPase complex. Removal of F1 natural inhibitor or of F1 does not affect the spectrum of NCCD bound to fragments, while the removal of oligomycin sensitivity-conferring protein produces an increase in the extreme splitting. Oligomycin sensitivity-conferring protein may thus interact with the NCCD binding component of the membrane. The isolation of the NCCD-binding proteolipid results in a large increase in the mobility of the label, but addition of dipalmitoyllecithin decreases the mobility of the label to the original level. Phospholipids are thus necessary to keep the NCCD-binding proteolipid in the native conformation.", "contents": "Molecular interactions of adenosine triphosphatase with the mitochondrial membrane as revealed by a spin label study. Mitochondrial ATPase complex has been spin-labeled in the membrane using the inhibitor N-(2,2,6,6-tetramethylpeperidyl-1-OXYL)-N(cyclohexyl)carbodiimide (nccd). the amount of NCCD bound to mitochondrial fragments is 0.5 nmol/mg and cannot be dialyzed or extracted with ether, chloroform, or methanol. The electron paramagnetic resonance spectrum of NCCD bound to fragments is pH-sensitive, a greater label immobilization occurring at pH values lower or higher than 7. Ether extraction removes the ATPase inhibition by NCCD without detaching the label. This effect appears to be the consequence of the dislocation of some components of the ATPase complex. Removal of F1 natural inhibitor or of F1 does not affect the spectrum of NCCD bound to fragments, while the removal of oligomycin sensitivity-conferring protein produces an increase in the extreme splitting. Oligomycin sensitivity-conferring protein may thus interact with the NCCD binding component of the membrane. The isolation of the NCCD-binding proteolipid results in a large increase in the mobility of the label, but addition of dipalmitoyllecithin decreases the mobility of the label to the original level. Phospholipids are thus necessary to keep the NCCD-binding proteolipid in the native conformation."}
{"id": "PMID:238976", "title": "Stimulation of tyrosine aminotransferase activity by dl-alpha-methyltryptophan.", "content": "DL-alpha-Methyltryptophan (alphaMeTrp), a synthetic analogue of tryptophan, has been found to be a potent inducer of hepatic tyrosine aminotransferase activity in the adrenalectomized rat. alphaMeTrp is inactive in vitro. Unlike the action of other known inducers (tryptophan, hydrocortisone, adenosine cyclic 3:5-monophosphate, and glucagon), maximal stimulation of enzyme activity occurs only 16 to 30 hours after alphaMeTrp administration and the activity is still elevated at 96 hours. Only the L isomer of alphaMeTrp is active, and addition of a hydroxyl group to position 5 of the indole ring renders an inactive compound. The induction can be prevented by actinomycin D or cycloheximide but not galactosamine. Administration of alphaMeTrp together with hydrocortisone produced an additive stimulation of enzyme activity. alphaMeTrp given along with glucagon or adenosine cyclic 3:5-monophosphate caused a further but not additive increase in enzyme activity. Tryptophan given along with alphaMeTrp promoted no extra stimulation whatsoever. These data indicate that alphaMeTrp and tryptophan may act via a common pathway which in part requires RNA synthesis. Other enzymes, namely alanine and aspartate aminotransferase, ornithine aminotransferase, ornithine carbamoyltransferase, serine dehydratase, and histidine ammonialyase, were not affected by treatment of rats with alphaMeTrp.", "contents": "Stimulation of tyrosine aminotransferase activity by dl-alpha-methyltryptophan. DL-alpha-Methyltryptophan (alphaMeTrp), a synthetic analogue of tryptophan, has been found to be a potent inducer of hepatic tyrosine aminotransferase activity in the adrenalectomized rat. alphaMeTrp is inactive in vitro. Unlike the action of other known inducers (tryptophan, hydrocortisone, adenosine cyclic 3:5-monophosphate, and glucagon), maximal stimulation of enzyme activity occurs only 16 to 30 hours after alphaMeTrp administration and the activity is still elevated at 96 hours. Only the L isomer of alphaMeTrp is active, and addition of a hydroxyl group to position 5 of the indole ring renders an inactive compound. The induction can be prevented by actinomycin D or cycloheximide but not galactosamine. Administration of alphaMeTrp together with hydrocortisone produced an additive stimulation of enzyme activity. alphaMeTrp given along with glucagon or adenosine cyclic 3:5-monophosphate caused a further but not additive increase in enzyme activity. Tryptophan given along with alphaMeTrp promoted no extra stimulation whatsoever. These data indicate that alphaMeTrp and tryptophan may act via a common pathway which in part requires RNA synthesis. Other enzymes, namely alanine and aspartate aminotransferase, ornithine aminotransferase, ornithine carbamoyltransferase, serine dehydratase, and histidine ammonialyase, were not affected by treatment of rats with alphaMeTrp."}
{"id": "PMID:238977", "title": "A transport system for phosphoenolpyruvate, 2-phosphoglycerate, and 3-phosphoglycerate in Salmonella typhimurium.", "content": "Salmonella typhimurium strain LT-2 was found to utilize phosphoenolpyruvate, 2-phosphoglycerate, and 3-phosphoglycerate as sole sources of carbon and energy for growth, but Escherichia coli strains did not. The following evidence suggests that this growth difference was due to the presence in Salmonella cells of an inducible phosphoglycerate permease distinct from previously studied transport systems: (a) The ability of cells to take up 3-phospho[14-C]glycerate was induced by growth in the presence of phosphoenolpyruvate, 2-phosphoglycerate, or 3-phosphoglycerate, but not glycerate, alpha-glycerophosphate, or other carbon sources tested. (b) Uptake of 3-phospho[14-C]glycerate was strongly inhibited by the three nonradioactive inducers of 3-phosphoglycerate uptake, but not by glycerate or alpha-glycerophosphate. (c) Mutants which lost the ability to utilize and take up 3-phosphoglycerate simultaneously lost the ability to utilize 2-phosphoglycerate and phosphoenolpyruvate, but not other compounds tested. (d) Mutant strains which constitutively synthesized the phosphoglycerate transport system could use both phosphoglycerates and phosphoenolpyruvate as sole sources of phosphate at low substrate concentrations. (e) A strain lacking alkaline and acid phosphatases could still grow with 3-phosphoglycerate as sole carbon source. Maximal rates of 3-phospho[14-C]glycerate uptake occurred at pH 6 in the presence of an exogenous energy source. The apparent Km for 3-phosphoglycerate uptake under these conditions was about 10-minus 4 M. The maximal uptake rate (but not the Km) was dependent on potassium ions. Although synthesis of the phosphoglycerate transport system appeared to be under adenosine 3:5-monophosphate control, glucose repressed induction only slightly. The genes controlling synthesis of the phosphoglycerate transport system (pgt genes) appeared to map at about 74 min on the Salmonella chromosome.", "contents": "A transport system for phosphoenolpyruvate, 2-phosphoglycerate, and 3-phosphoglycerate in Salmonella typhimurium. Salmonella typhimurium strain LT-2 was found to utilize phosphoenolpyruvate, 2-phosphoglycerate, and 3-phosphoglycerate as sole sources of carbon and energy for growth, but Escherichia coli strains did not. The following evidence suggests that this growth difference was due to the presence in Salmonella cells of an inducible phosphoglycerate permease distinct from previously studied transport systems: (a) The ability of cells to take up 3-phospho[14-C]glycerate was induced by growth in the presence of phosphoenolpyruvate, 2-phosphoglycerate, or 3-phosphoglycerate, but not glycerate, alpha-glycerophosphate, or other carbon sources tested. (b) Uptake of 3-phospho[14-C]glycerate was strongly inhibited by the three nonradioactive inducers of 3-phosphoglycerate uptake, but not by glycerate or alpha-glycerophosphate. (c) Mutants which lost the ability to utilize and take up 3-phosphoglycerate simultaneously lost the ability to utilize 2-phosphoglycerate and phosphoenolpyruvate, but not other compounds tested. (d) Mutant strains which constitutively synthesized the phosphoglycerate transport system could use both phosphoglycerates and phosphoenolpyruvate as sole sources of phosphate at low substrate concentrations. (e) A strain lacking alkaline and acid phosphatases could still grow with 3-phosphoglycerate as sole carbon source. Maximal rates of 3-phospho[14-C]glycerate uptake occurred at pH 6 in the presence of an exogenous energy source. The apparent Km for 3-phosphoglycerate uptake under these conditions was about 10-minus 4 M. The maximal uptake rate (but not the Km) was dependent on potassium ions. Although synthesis of the phosphoglycerate transport system appeared to be under adenosine 3:5-monophosphate control, glucose repressed induction only slightly. The genes controlling synthesis of the phosphoglycerate transport system (pgt genes) appeared to map at about 74 min on the Salmonella chromosome."}
{"id": "PMID:238978", "title": "Functional deacylases of pigeon liver fatty acid synthetase complex.", "content": "Fatty acid synthetase complex (Mr = 500,000) purified from pigeon liver homogenates is inactivated by phenylmethylsulfonyl fluoride. A well characterized inhibitor of serine esterases. Pseudounimolecular kinetics are followed at all inhibitor concentrations studied (0.05 to 1.0 mM). The second order rate constant obtained at pH 7.0, 30 degrees in 0.05 M potassium phosphate, 1 mM EDTA is 250 plus or minus 10 M-1 min-1 and appears to be independent of pH between 6 and 7.9. The inactivation of the enzyme complex appears to be selective since only one of the several component enzymes of fatty acid synthesis, palmityl-CoA deacylase, is inhibited. Acetyl- and malonyl-CoA-pantetheine transacylase activities as well as the kinetics of the reduction and dehydration steps are nearly identical for the native and the modified enzymes. The rate of approach of the condensation-CO2 exchange reaction (substrates: hexanoyl-CoA, malonyl-CoA, CoA, and H14CO3-) is slightly slower in the modified enzyme, though this change is not large enough to account for total loss of activity for fatty acid synthesis. The rate of loss of palmityl-CoA deacylase activity at a constant inhibitor concentration follows biphasic kinetics. Complete inactivation is achieved only after 2 mol of the inhibitor are bound per mol of the enzyme complex. Acetyl-, butyryl-, and hexanoyl-CoA thioesters (at 1.0 mM concentrations) protect the enzyme complex against inactivation by phenylmethylsulfonyl fluoride whereas CoA has no effect. Malonyl-CoA on the other hand, promotes inhibitor-mediated inactivation. Of the N-acetyl cysteamine derivatives tested, S-acetyl-N-acetyl cysteamine (at 10 mM) gives almost complete protection against inactivation whereas S-acetoacetyl-, S-beta-hydroxybutyryl-, and S-crotonyl-N-acetyl cysteamine thioesters exhibit either slight or no protection. These data demonstrate that phenylmethylsulfonyl fluoride is a selective reagent for the inactivation of functional fatty acyl deacylase component(s) of the pigeon liver fatty acid synthetase complex, and that it has no effect on malonyl or acetyl transacylases. The data are also in accord with the postulation that the inhibitor interacts at two catalytic centers of the enzyme complex. Furthermore, the patterns of protective effects shown by saturated acyl-CoA asters and malonyl-CoA point to different mechanisms of deacylation for these esters.", "contents": "Functional deacylases of pigeon liver fatty acid synthetase complex. Fatty acid synthetase complex (Mr = 500,000) purified from pigeon liver homogenates is inactivated by phenylmethylsulfonyl fluoride. A well characterized inhibitor of serine esterases. Pseudounimolecular kinetics are followed at all inhibitor concentrations studied (0.05 to 1.0 mM). The second order rate constant obtained at pH 7.0, 30 degrees in 0.05 M potassium phosphate, 1 mM EDTA is 250 plus or minus 10 M-1 min-1 and appears to be independent of pH between 6 and 7.9. The inactivation of the enzyme complex appears to be selective since only one of the several component enzymes of fatty acid synthesis, palmityl-CoA deacylase, is inhibited. Acetyl- and malonyl-CoA-pantetheine transacylase activities as well as the kinetics of the reduction and dehydration steps are nearly identical for the native and the modified enzymes. The rate of approach of the condensation-CO2 exchange reaction (substrates: hexanoyl-CoA, malonyl-CoA, CoA, and H14CO3-) is slightly slower in the modified enzyme, though this change is not large enough to account for total loss of activity for fatty acid synthesis. The rate of loss of palmityl-CoA deacylase activity at a constant inhibitor concentration follows biphasic kinetics. Complete inactivation is achieved only after 2 mol of the inhibitor are bound per mol of the enzyme complex. Acetyl-, butyryl-, and hexanoyl-CoA thioesters (at 1.0 mM concentrations) protect the enzyme complex against inactivation by phenylmethylsulfonyl fluoride whereas CoA has no effect. Malonyl-CoA on the other hand, promotes inhibitor-mediated inactivation. Of the N-acetyl cysteamine derivatives tested, S-acetyl-N-acetyl cysteamine (at 10 mM) gives almost complete protection against inactivation whereas S-acetoacetyl-, S-beta-hydroxybutyryl-, and S-crotonyl-N-acetyl cysteamine thioesters exhibit either slight or no protection. These data demonstrate that phenylmethylsulfonyl fluoride is a selective reagent for the inactivation of functional fatty acyl deacylase component(s) of the pigeon liver fatty acid synthetase complex, and that it has no effect on malonyl or acetyl transacylases. The data are also in accord with the postulation that the inhibitor interacts at two catalytic centers of the enzyme complex. Furthermore, the patterns of protective effects shown by saturated acyl-CoA asters and malonyl-CoA point to different mechanisms of deacylation for these esters."}
{"id": "PMID:238979", "title": "Lysophospholipase of Escherichia coli.", "content": "A lysophospholipase from Escherichia coli cells was purified about 1,500-fold to near homogeneity by extraction with Tris-HCl buffer, streptomycin treatment, (NH4)2SO4 fractionation, column chromatographies on Sephadex G-200, DEAE-cellulose and hydroxylapatite-cellulose, and polyacrylamide gel electrophoresis. The final preparation had a molecular weight of 39,500 plus or minus 500. The enzyme hydrolyzes 1-acylglycerylphosphorylethanolamine, 2-acylglycerylphosphorylethanoiamine, and 1-acylglycerylphosphorylglycerol, but does not attack diacylphospholipids with long chain fatty acids, such as phosphatidylethanolamine and phosphatidylglycerol. The enzyme does not show any esterase activity against p-nitrophenyl acetate or palmitate. Although it does not hydrolyze triacylglycerol or diacylglycerol, it hydrolyzes 1-acylglycerol at almost the same rate as 1-acyl-sn-glycerol-3-phosphorylethanolamine. Results indicated that the acyl-hydrolyzing activities toward monoacyl-glycerylphosphorylethanolamine and monoacylglycerol belong to the same enzyme. In general, acidic and nonionic detergents inhibited the reaction. This lysophospholipase preparation hydrolyzes the monomolecular and micellar forms of lysophospholipids as well as of monoacylglycerol. The monomolecular and micellar forms of Triton X-100 both inhibited the hydrolyses of lysophospholipids and monoacylglycerol.", "contents": "Lysophospholipase of Escherichia coli. A lysophospholipase from Escherichia coli cells was purified about 1,500-fold to near homogeneity by extraction with Tris-HCl buffer, streptomycin treatment, (NH4)2SO4 fractionation, column chromatographies on Sephadex G-200, DEAE-cellulose and hydroxylapatite-cellulose, and polyacrylamide gel electrophoresis. The final preparation had a molecular weight of 39,500 plus or minus 500. The enzyme hydrolyzes 1-acylglycerylphosphorylethanolamine, 2-acylglycerylphosphorylethanoiamine, and 1-acylglycerylphosphorylglycerol, but does not attack diacylphospholipids with long chain fatty acids, such as phosphatidylethanolamine and phosphatidylglycerol. The enzyme does not show any esterase activity against p-nitrophenyl acetate or palmitate. Although it does not hydrolyze triacylglycerol or diacylglycerol, it hydrolyzes 1-acylglycerol at almost the same rate as 1-acyl-sn-glycerol-3-phosphorylethanolamine. Results indicated that the acyl-hydrolyzing activities toward monoacyl-glycerylphosphorylethanolamine and monoacylglycerol belong to the same enzyme. In general, acidic and nonionic detergents inhibited the reaction. This lysophospholipase preparation hydrolyzes the monomolecular and micellar forms of lysophospholipids as well as of monoacylglycerol. The monomolecular and micellar forms of Triton X-100 both inhibited the hydrolyses of lysophospholipids and monoacylglycerol."}
{"id": "PMID:238980", "title": "Evidence for an essential histidine in carboxypeptidase Y. Reaction with the chloromethyl ketone derivative of benzyloxycarbonyl-L-phenylalanine.", "content": "The possible role of histidine residues in the catalytic function of carboxypeptidase Y from bakers' yeast has been investigated using site-specific reagents. Among the reagents tested, benzyloxy-L-phenylalanylchloromethane (Z-PheCH2Cl) was the most powerful inhibitor of the enzyme. It irreversibly inactivated both the peptidase and esterase activities with an apparent second order rate constant of 3.8 M-minus 1 S-minus 1; the D isomer caused essentially no effect on either activity. Inhibition by L-Z-PheCH2Cl, the reaction retarded by certain competitive inhibitors of the enzyme. Using radioactive L-Z-PheCH2Cl, the reaction with the enzyme was shown to be essentially stoichiometric. Diisopropylphosphorofluoridate (iPr2PF)-inactivated enzyme failed to react with Z-PheCH2Cl, and conversely, the Z-PheCH2Cl-inhibited enzyme failed to react with radioactive iPr2PF. Amino acid analyses of the Z-PheCH2Cl-inactivated enzyme revealed the loss of essentially 1 residue, with a concomitant yield of a 0.62 residue of N-t-carboxymethylhistidine. Since carboxypeptidase Y has a reactive serine at its active center, we concluded from these results that the mechanism involves a charge-relay system in the hydrolysis of peptide and ester substrates, as in chymotrypsin. An -SH group of carboxypeptidase Y was not affected during the reaction with L-Z-PheCH2Cl. The generic name \"serine carboxypeptidase\" has been proposed for carboxypeptidase Y and for the iPr2PF-sensitive carboxypeptidases from plants, molds, and animal tissues, in order to distinguish them from \"metal carboxypeptidase\" to which carboxypeptidase A (EC 3.4.12.2) and B (EC 3.4.12.3) belong.", "contents": "Evidence for an essential histidine in carboxypeptidase Y. Reaction with the chloromethyl ketone derivative of benzyloxycarbonyl-L-phenylalanine. The possible role of histidine residues in the catalytic function of carboxypeptidase Y from bakers' yeast has been investigated using site-specific reagents. Among the reagents tested, benzyloxy-L-phenylalanylchloromethane (Z-PheCH2Cl) was the most powerful inhibitor of the enzyme. It irreversibly inactivated both the peptidase and esterase activities with an apparent second order rate constant of 3.8 M-minus 1 S-minus 1; the D isomer caused essentially no effect on either activity. Inhibition by L-Z-PheCH2Cl, the reaction retarded by certain competitive inhibitors of the enzyme. Using radioactive L-Z-PheCH2Cl, the reaction with the enzyme was shown to be essentially stoichiometric. Diisopropylphosphorofluoridate (iPr2PF)-inactivated enzyme failed to react with Z-PheCH2Cl, and conversely, the Z-PheCH2Cl-inhibited enzyme failed to react with radioactive iPr2PF. Amino acid analyses of the Z-PheCH2Cl-inactivated enzyme revealed the loss of essentially 1 residue, with a concomitant yield of a 0.62 residue of N-t-carboxymethylhistidine. Since carboxypeptidase Y has a reactive serine at its active center, we concluded from these results that the mechanism involves a charge-relay system in the hydrolysis of peptide and ester substrates, as in chymotrypsin. An -SH group of carboxypeptidase Y was not affected during the reaction with L-Z-PheCH2Cl. The generic name \"serine carboxypeptidase\" has been proposed for carboxypeptidase Y and for the iPr2PF-sensitive carboxypeptidases from plants, molds, and animal tissues, in order to distinguish them from \"metal carboxypeptidase\" to which carboxypeptidase A (EC 3.4.12.2) and B (EC 3.4.12.3) belong."}
{"id": "PMID:238981", "title": "Structural, kinetic, and renaturation properties of an induced hydroxypyruvate reductase from Pseudomonas acidovorans.", "content": "A hydroxypyruvate reductase has been induced in Pseudomonas acidovorans by growth on glyoxylate. The enzyme has been purified to homogeneity as assessed by the criteria of analytical ultracentrifugation and analytical disc gel electrophoresis. It has a molecular weight of approximately 85,000 and is composed of two identical subunits. The subunits are not interconnected by disulfide bonds although the enzyme has 4 mol of half-cystine per mol of enzyme. The enzyme catalyzes the reversible conversion of hydroxypyruvate to D(minus)-glycerate in the presence of NADH. Glyoxylate cannot replace hydroxypyruvate as a substrate and is a competitive inhibitor of hydroxypyruvate reduction. The activity of the enzyme toward hydroxypyruvate is anion-modulated; the activity of the enzyme toward D(minus)-glycerate is unaffected by anions but is increased by tris-(hydroxymethyl)aminomethane. The subunits of the induced hydroxypyruvate reductase can be renatured. After the enzyme is dissociated in solutions of 6.0 M guanidine hydrochloride containing 0.1 M 2-mercaptoethanol, optimum renaturation occurs when subunits are diluted into a renaturation solvent consisting of 0.04 M Trischloride, pH 7.4, containing 25% glycerol, 25 mM 2-mercaptoethanol, and 0.14 MM NADH. NAD is an inhibitor of renaturation and therefore cannot substitute for NADH. The optimal temperature of dilution and subsequent incubation is 15 degrees, and increases in protein concentration up to 1.2 mg/ml, the highest concentration tested, improve both the rate of renaturation and the yield of active material. The half-time of renaturation at a protein concentration of 1.2 mg/ml was 1 min. The kinetics of renaturation is second order, i.e., is compatible with a bimolecular reaction preducted by the association of two similar subunits. The physical and kinetic parameters of the renatured protein are the same as those of the native enzyme.", "contents": "Structural, kinetic, and renaturation properties of an induced hydroxypyruvate reductase from Pseudomonas acidovorans. A hydroxypyruvate reductase has been induced in Pseudomonas acidovorans by growth on glyoxylate. The enzyme has been purified to homogeneity as assessed by the criteria of analytical ultracentrifugation and analytical disc gel electrophoresis. It has a molecular weight of approximately 85,000 and is composed of two identical subunits. The subunits are not interconnected by disulfide bonds although the enzyme has 4 mol of half-cystine per mol of enzyme. The enzyme catalyzes the reversible conversion of hydroxypyruvate to D(minus)-glycerate in the presence of NADH. Glyoxylate cannot replace hydroxypyruvate as a substrate and is a competitive inhibitor of hydroxypyruvate reduction. The activity of the enzyme toward hydroxypyruvate is anion-modulated; the activity of the enzyme toward D(minus)-glycerate is unaffected by anions but is increased by tris-(hydroxymethyl)aminomethane. The subunits of the induced hydroxypyruvate reductase can be renatured. After the enzyme is dissociated in solutions of 6.0 M guanidine hydrochloride containing 0.1 M 2-mercaptoethanol, optimum renaturation occurs when subunits are diluted into a renaturation solvent consisting of 0.04 M Trischloride, pH 7.4, containing 25% glycerol, 25 mM 2-mercaptoethanol, and 0.14 MM NADH. NAD is an inhibitor of renaturation and therefore cannot substitute for NADH. The optimal temperature of dilution and subsequent incubation is 15 degrees, and increases in protein concentration up to 1.2 mg/ml, the highest concentration tested, improve both the rate of renaturation and the yield of active material. The half-time of renaturation at a protein concentration of 1.2 mg/ml was 1 min. The kinetics of renaturation is second order, i.e., is compatible with a bimolecular reaction preducted by the association of two similar subunits. The physical and kinetic parameters of the renatured protein are the same as those of the native enzyme."}
{"id": "PMID:238982", "title": "Location of deuterium oxide solvent isotope effects in the glutamate dehydrogenase reaction.", "content": "Stopped flow studies of D2O kinetic solvent isotope effects on the reaction catalyzed by L-glutamate dehydrogenase reveal, in addition to several effects apparently attributable simply to pKa shifts, a 2-fold pH-independent effect on the velocity of the steady state oxidative deamination of L-glutamate by enzyme and NADP. Comparable pH-independent D2O kinetic solvent isotope effects are seen both in a transient phase of the reaction in which alpha-ketoglutarate is displaced by L-glutamate from an enzyme-NADPH-alpha-ketoglutarate (product) complex and in an analogous model reaction in which alpha-ketoglutarate is displaced by D-glutamate. These results suggest that alpha-ketoglutarate dissociation from an enzyme-NADPH-alpha-ketoglutarate complex is rate-limiting in the steady state.", "contents": "Location of deuterium oxide solvent isotope effects in the glutamate dehydrogenase reaction. Stopped flow studies of D2O kinetic solvent isotope effects on the reaction catalyzed by L-glutamate dehydrogenase reveal, in addition to several effects apparently attributable simply to pKa shifts, a 2-fold pH-independent effect on the velocity of the steady state oxidative deamination of L-glutamate by enzyme and NADP. Comparable pH-independent D2O kinetic solvent isotope effects are seen both in a transient phase of the reaction in which alpha-ketoglutarate is displaced by L-glutamate from an enzyme-NADPH-alpha-ketoglutarate (product) complex and in an analogous model reaction in which alpha-ketoglutarate is displaced by D-glutamate. These results suggest that alpha-ketoglutarate dissociation from an enzyme-NADPH-alpha-ketoglutarate complex is rate-limiting in the steady state."}
{"id": "PMID:238983", "title": "Identification of a new DNA polymerase activity in human KB cells.", "content": "We have isolated and partially characterized a new DNA polymerase activity from the purified nuclear fraction of cultured human KB cells. The physical and chemical properties of this enzyme which we have designated DNA polymerase N3 define it as a unique entity that can be distinguished from the several classes of eukaryotic D-DNA and R-DNA polymerase activity that have been recognized to date.", "contents": "Identification of a new DNA polymerase activity in human KB cells. We have isolated and partially characterized a new DNA polymerase activity from the purified nuclear fraction of cultured human KB cells. The physical and chemical properties of this enzyme which we have designated DNA polymerase N3 define it as a unique entity that can be distinguished from the several classes of eukaryotic D-DNA and R-DNA polymerase activity that have been recognized to date."}
{"id": "PMID:238984", "title": "Acceleration of tetramer formation by the binding of inositol hexaphosphate to hemoglobin dimers.", "content": "The aggregation of deoxyhemoglobin dimers was studied by dropping the pH of a dilute solution of deoxyhemoglobin originally at high pH. In the presence of inositol hexaphosphate, a sharp increase in the rate of dimer association was observed. At higher concentrations of the phosphate, the rate decreased to a value close to that seen in the absence of phosphate. These observations require that inositol hexaphosphate binds to deoxyhemoglobin dimers. The dependence of the aggregation rate on phosphate concentration occurs because the reaction of a dimer containing bound phosphate with a phosphate-free dimer is 30 to 50 times faster than either the association of phosphate-free dimers or the association of dimers both containing bound phosphate.", "contents": "Acceleration of tetramer formation by the binding of inositol hexaphosphate to hemoglobin dimers. The aggregation of deoxyhemoglobin dimers was studied by dropping the pH of a dilute solution of deoxyhemoglobin originally at high pH. In the presence of inositol hexaphosphate, a sharp increase in the rate of dimer association was observed. At higher concentrations of the phosphate, the rate decreased to a value close to that seen in the absence of phosphate. These observations require that inositol hexaphosphate binds to deoxyhemoglobin dimers. The dependence of the aggregation rate on phosphate concentration occurs because the reaction of a dimer containing bound phosphate with a phosphate-free dimer is 30 to 50 times faster than either the association of phosphate-free dimers or the association of dimers both containing bound phosphate."}
{"id": "PMID:238985", "title": "3-Hydroxy-3-methylglutaryl coenzyme A synthase. Evidence for an acetyl-S-enzyme intermediate and identification of a cysteinyl sulfhydryl as the site of acetylation.", "content": "Homogeneous liver 3-hydroxy-3-methylglutaryl coenzyme A synthase, which catalyzes the condensation of acetyl-CoA with acetoacetyl-CoA to form 3-hydroxy-3-methylglutaryl-CoA, also carries out: (a) a rapid transacetylation from acetyl-CoA to 31-dephospho-CoA and (b) a slow hydrolysis of acetyl-CoA to acetate and CoA. Transacetylation and hydrolysis occur at 50 and 1 percent, respectively, the rate of the synthasecatalyzed condensation reaction. It appears that an acetyl-enzyme intermediate is involved in the transacetylase and hydrolase reactions of 3-hydroxy-3-methylglutaryl-CoA synthase, as well as in the over-all condensation process. Covalent binding to the enzyme of a [14C]acetyl group contributed by [1(-14)C]acetyl-CoA is indicated by migration of the [14C]acetyl group with the dissociated synthase upon electrophoresis in dodecyl sulfate-urea and by precipitation of [14C]acetyl-enzyme with trichloroacetic acid. At 0 degrees and a saturating level of acetyl-CoA, the synthase is rapidly (less than 20 s) acetylated yielding 0.6 acetyl group/enzyme dimer. Performic acid oxidation completely deacetylates the enzyme, suggesting the site of acetylation to be a cysteinyl sulfhydryl group. Proteolytic digestion of [14C]acetyl-S-enzyme under conditions favorable for intramolecular S to N acetyl group transfer quantitatively liberates a labeled derivative with a [14C]acetyl group stable to performic acid oxidation. The labeled oxidation product is identified as N-[14C]acetylcysteic acid, thus demonstrating a cysteinyl sulfhydryl group as the original site of acetylation. The ability of the acetylated enzyme, upon addition of acetoacetyl-CoA, to form 3-hydroxy-3-methylglutaryl-CoA indicates that the acetylated cysteine residue is at the catalytic site.", "contents": "3-Hydroxy-3-methylglutaryl coenzyme A synthase. Evidence for an acetyl-S-enzyme intermediate and identification of a cysteinyl sulfhydryl as the site of acetylation. Homogeneous liver 3-hydroxy-3-methylglutaryl coenzyme A synthase, which catalyzes the condensation of acetyl-CoA with acetoacetyl-CoA to form 3-hydroxy-3-methylglutaryl-CoA, also carries out: (a) a rapid transacetylation from acetyl-CoA to 31-dephospho-CoA and (b) a slow hydrolysis of acetyl-CoA to acetate and CoA. Transacetylation and hydrolysis occur at 50 and 1 percent, respectively, the rate of the synthasecatalyzed condensation reaction. It appears that an acetyl-enzyme intermediate is involved in the transacetylase and hydrolase reactions of 3-hydroxy-3-methylglutaryl-CoA synthase, as well as in the over-all condensation process. Covalent binding to the enzyme of a [14C]acetyl group contributed by [1(-14)C]acetyl-CoA is indicated by migration of the [14C]acetyl group with the dissociated synthase upon electrophoresis in dodecyl sulfate-urea and by precipitation of [14C]acetyl-enzyme with trichloroacetic acid. At 0 degrees and a saturating level of acetyl-CoA, the synthase is rapidly (less than 20 s) acetylated yielding 0.6 acetyl group/enzyme dimer. Performic acid oxidation completely deacetylates the enzyme, suggesting the site of acetylation to be a cysteinyl sulfhydryl group. Proteolytic digestion of [14C]acetyl-S-enzyme under conditions favorable for intramolecular S to N acetyl group transfer quantitatively liberates a labeled derivative with a [14C]acetyl group stable to performic acid oxidation. The labeled oxidation product is identified as N-[14C]acetylcysteic acid, thus demonstrating a cysteinyl sulfhydryl group as the original site of acetylation. The ability of the acetylated enzyme, upon addition of acetoacetyl-CoA, to form 3-hydroxy-3-methylglutaryl-CoA indicates that the acetylated cysteine residue is at the catalytic site."}
{"id": "PMID:238986", "title": "Changes in nuclear proteins of rat testis cells separated by velocity sedimentation.", "content": "The technique of velocity sedimentation at unit gravity has been used to separate rat testis cell suspensions into fractions enriched in particular cell types. Changes in the nuclear proteins from the various fractions have been characterized by polyacrylamide gel electrophoresis, and correlated with the changing morphology of the nucleus during spermatogenesis. The most striking alterations in both protein composition and nuclear morphology occur during spermatid maturation as both histone and non-histone proteins are replaced by highly basic, low molecular weight, spermatidal proteins. This replacement process is accompanied by a quantitative reduction in both histone and non-histone proteins. The synthesis of at least three basic proteins has been identified with late stage spermatids. One of these proteins is a highly basic sperm-specific protein containing high levels of cyst(e)ine and arginine. A second protein synthesized in late stage spermatids is lysine rich, while the third protein contains cyst(e)ine and co-migrates with histone F2a1 on acid-urea polyacrylamide gels. The changes in protein composition of rat testis nuclei after irradiation or hypophysectomy reflect the resulting changes in the cellular composition of the testis. After selective elimination of the germinal cells by irradiation, the electrophoretic pattern of acid-soluble proteins from the testis is very similar to that of somatic tissue. Thus, the cellular specificity of nuclear proteins demonstrated here using cell separation techniques is also apparent following treatments which selectively alter the cellular composition of the testis.", "contents": "Changes in nuclear proteins of rat testis cells separated by velocity sedimentation. The technique of velocity sedimentation at unit gravity has been used to separate rat testis cell suspensions into fractions enriched in particular cell types. Changes in the nuclear proteins from the various fractions have been characterized by polyacrylamide gel electrophoresis, and correlated with the changing morphology of the nucleus during spermatogenesis. The most striking alterations in both protein composition and nuclear morphology occur during spermatid maturation as both histone and non-histone proteins are replaced by highly basic, low molecular weight, spermatidal proteins. This replacement process is accompanied by a quantitative reduction in both histone and non-histone proteins. The synthesis of at least three basic proteins has been identified with late stage spermatids. One of these proteins is a highly basic sperm-specific protein containing high levels of cyst(e)ine and arginine. A second protein synthesized in late stage spermatids is lysine rich, while the third protein contains cyst(e)ine and co-migrates with histone F2a1 on acid-urea polyacrylamide gels. The changes in protein composition of rat testis nuclei after irradiation or hypophysectomy reflect the resulting changes in the cellular composition of the testis. After selective elimination of the germinal cells by irradiation, the electrophoretic pattern of acid-soluble proteins from the testis is very similar to that of somatic tissue. Thus, the cellular specificity of nuclear proteins demonstrated here using cell separation techniques is also apparent following treatments which selectively alter the cellular composition of the testis."}
{"id": "PMID:238987", "title": "Purification and properties of citrate lyase from Streptococcus diacetilactis.", "content": "Citrate lyase from Streptococcus diacetilactis has been purified to yield a protein that was homogeneous as judged by sedimentation velocity and sedimentation equilibrium experiments. The enzyme's sedimentation coefficient is 16.8 S and its molecular weight is around 585,000. It contains three nonidentical subunits of about 53,000, 34,000, and 10,000 daltons. The enzyme in its active form contains an acetyl group which turns over during the citrate cleavage reaction. Removal of the acetyl group inactivates the enzyme. The deacetyl enzyme can be partially reactivated by acetylation with acetic anhydride. The enzyme undergoes slow \"reaction-inactivation.\" The rate of inactivation is first order and the rate constant of inactivation is much lower than that for a similar inactivation process of the citrate lyase from Klebsiella aerogenes. Like the latter enzyme it contains stoichiometric amounts of phosphopantothenate. The enzyme is inactivated at pH greater than 8.1 and the presence of citrate provides protection against this inactivation. Sedimentation studies of the enzyme at pH 8.7 indicate that the enzyme is dissociated, which may account for the inactivation. The enzyme is immunologically different from citrate lyases of K. aerogenes and Escherichia coli.", "contents": "Purification and properties of citrate lyase from Streptococcus diacetilactis. Citrate lyase from Streptococcus diacetilactis has been purified to yield a protein that was homogeneous as judged by sedimentation velocity and sedimentation equilibrium experiments. The enzyme's sedimentation coefficient is 16.8 S and its molecular weight is around 585,000. It contains three nonidentical subunits of about 53,000, 34,000, and 10,000 daltons. The enzyme in its active form contains an acetyl group which turns over during the citrate cleavage reaction. Removal of the acetyl group inactivates the enzyme. The deacetyl enzyme can be partially reactivated by acetylation with acetic anhydride. The enzyme undergoes slow \"reaction-inactivation.\" The rate of inactivation is first order and the rate constant of inactivation is much lower than that for a similar inactivation process of the citrate lyase from Klebsiella aerogenes. Like the latter enzyme it contains stoichiometric amounts of phosphopantothenate. The enzyme is inactivated at pH greater than 8.1 and the presence of citrate provides protection against this inactivation. Sedimentation studies of the enzyme at pH 8.7 indicate that the enzyme is dissociated, which may account for the inactivation. The enzyme is immunologically different from citrate lyases of K. aerogenes and Escherichia coli."}
{"id": "PMID:238988", "title": "On the mechanism of activation of fat cell adenylate cyclase by guanine nucleotides. An explanation for the biphasic inhibitory and stimulatory effects of the nucleotides and the role of hormones.", "content": "Adenylate cyclase activity in purified plasma membranes from rat fat cells displays transient kinetic characteristics in the absence and presence of guanyl=5'=yl imidodiphosphate (Gpp(NH)p). Gpp(NH)p causes immediate inhibition of enzyme activity; the inhibitory phase is followed by a slow increase in activity which, depending on incubation temperature, exceeds activity stimulated in the presence of hormones (glucagon, secretin, epinephrine, or adrenocorticotropin). Basal activity displays an initial high rate of activity which decays to a low state of activity within 2 min of incubation. Hormones do not alter the initial rate but prevent the decay in enzyme activity. The inhibitory phase of Gpp(NH)p action and the previously reported (Harwood, J.P., Low, H., and Rodbell, M. (1973) J. Biol. Chem. 248, 6239-6245) inhibitory effects of GTP are abolished by increasing (Mg2+) and pH to 50 mM and 8.5, respectively. Under these conditions, Gpp(NH)p and GTP cause marked stimulation of activity, the stimulatory effect of Gpp(NH)p being greater than that of GTP both in the absence and presence of hormones...", "contents": "On the mechanism of activation of fat cell adenylate cyclase by guanine nucleotides. An explanation for the biphasic inhibitory and stimulatory effects of the nucleotides and the role of hormones. Adenylate cyclase activity in purified plasma membranes from rat fat cells displays transient kinetic characteristics in the absence and presence of guanyl=5'=yl imidodiphosphate (Gpp(NH)p). Gpp(NH)p causes immediate inhibition of enzyme activity; the inhibitory phase is followed by a slow increase in activity which, depending on incubation temperature, exceeds activity stimulated in the presence of hormones (glucagon, secretin, epinephrine, or adrenocorticotropin). Basal activity displays an initial high rate of activity which decays to a low state of activity within 2 min of incubation. Hormones do not alter the initial rate but prevent the decay in enzyme activity. The inhibitory phase of Gpp(NH)p action and the previously reported (Harwood, J.P., Low, H., and Rodbell, M. (1973) J. Biol. Chem. 248, 6239-6245) inhibitory effects of GTP are abolished by increasing (Mg2+) and pH to 50 mM and 8.5, respectively. Under these conditions, Gpp(NH)p and GTP cause marked stimulation of activity, the stimulatory effect of Gpp(NH)p being greater than that of GTP both in the absence and presence of hormones..."}
{"id": "PMID:238989", "title": "The mitochondrial malic enzymes. I. Submitochondrial localization and purification and properties of the NAD(P)+-dependent enzyme from adrenal cortex.", "content": "Rat and calf adrenal cortex homogenates were found to contain three different malic enzymes. Two were strictly NADP+-dependent and were localized, one each, in the cytosol and the mitochondrial fractions, respectively. These two enzymes appear to be identical to those described by Simpson and Estabrook (Simpson, E. R., and Estabrook, R. W. (1969) Arch. Biochem. Biophys. 129, 384-395). The third was NAD(P)+-linked and was present in the mitochondrial fraction only. All three malic enzymes separated as distinct bands during electrophoresis on 5 percent polyacrylamide slab gels at pH 9.0. Marker enzymes and the mitochondrial malic enzymes migrated together in intact mitochondria during sucrose density gradient centrifugations despite changes in the equilibrium position of the mitochondria promoted by energy-dependent calcium phosphate accumulation. In adrenal cortex mitochondria subfractionated by the method of Sottocasa et al. (SOTTOCASA, G.L., KUYLENSTIERNA, B., ERNSTER, L., and BERGSTAND, A. (1967) J. Cell Biol. 32, 415-438), both malic enzymes were associated with the inner membrane-matrix space. Sonication solubilized the two malic enzymes along with the matrix space marker enzymes. The NAD(P)+-dependent malic enzyme was purified 100-fold from calf adrenal cortex mitochondria. The final preparation was free of malic dehydrogenase, fumarase, the strictly NADP+-linked malic enzyme and adenylate kinase. Either Mn24 orMg2+ was required for activity and 1 mol of pyruvate was formed for each mole of NAD+ and NADP+ reduced. The pH optima with NAD+ and NADP+ were 6.5 tp 7.0 and 6.0 to 6.5, respectively. Michaelis-Menten kinetics were observed on the alkaline side. Fumarate, succinate, and isocitrate were positive and ATP and ADP were negative modulators of the regulatory enzyme. The modulators did not influence the stoichiometry and they were not metabolized during the reaction. Under Vmax conditions the ratios for the rate of NAD+:NADP+ reduction were 1.76 and 1.15 at pH 7.4 and 6.0, respectively. The apparent Michaelis constants also differed depending on the pH and the coenzyme. At pH 7.4 (in the presence of 5 mM fumarate) and at pH 6.0 (no fumarate) the Km values for (-)-malate, NAD+, and Mn2+ were 1.7, 0.16, and 0.15 mM, and 0.31, 0.06, and 0.09 mM, respectively. At pH 7.4 (5MM fumarate) and pH 6.0 (no fumarate), the Km values for (-)-malate, NADP+, and Mn2+ were 6.5, 0.62, and 0.59 mM, and 0.68. 0.12, and 0.31 mM, respectively. The apparent Ki values for ATP with NAD+ and NADP+ as coenzyme were 0.42 and 0.27 mM, respectively.", "contents": "The mitochondrial malic enzymes. I. Submitochondrial localization and purification and properties of the NAD(P)+-dependent enzyme from adrenal cortex. Rat and calf adrenal cortex homogenates were found to contain three different malic enzymes. Two were strictly NADP+-dependent and were localized, one each, in the cytosol and the mitochondrial fractions, respectively. These two enzymes appear to be identical to those described by Simpson and Estabrook (Simpson, E. R., and Estabrook, R. W. (1969) Arch. Biochem. Biophys. 129, 384-395). The third was NAD(P)+-linked and was present in the mitochondrial fraction only. All three malic enzymes separated as distinct bands during electrophoresis on 5 percent polyacrylamide slab gels at pH 9.0. Marker enzymes and the mitochondrial malic enzymes migrated together in intact mitochondria during sucrose density gradient centrifugations despite changes in the equilibrium position of the mitochondria promoted by energy-dependent calcium phosphate accumulation. In adrenal cortex mitochondria subfractionated by the method of Sottocasa et al. (SOTTOCASA, G.L., KUYLENSTIERNA, B., ERNSTER, L., and BERGSTAND, A. (1967) J. Cell Biol. 32, 415-438), both malic enzymes were associated with the inner membrane-matrix space. Sonication solubilized the two malic enzymes along with the matrix space marker enzymes. The NAD(P)+-dependent malic enzyme was purified 100-fold from calf adrenal cortex mitochondria. The final preparation was free of malic dehydrogenase, fumarase, the strictly NADP+-linked malic enzyme and adenylate kinase. Either Mn24 orMg2+ was required for activity and 1 mol of pyruvate was formed for each mole of NAD+ and NADP+ reduced. The pH optima with NAD+ and NADP+ were 6.5 tp 7.0 and 6.0 to 6.5, respectively. Michaelis-Menten kinetics were observed on the alkaline side. Fumarate, succinate, and isocitrate were positive and ATP and ADP were negative modulators of the regulatory enzyme. The modulators did not influence the stoichiometry and they were not metabolized during the reaction. Under Vmax conditions the ratios for the rate of NAD+:NADP+ reduction were 1.76 and 1.15 at pH 7.4 and 6.0, respectively. The apparent Michaelis constants also differed depending on the pH and the coenzyme. At pH 7.4 (in the presence of 5 mM fumarate) and at pH 6.0 (no fumarate) the Km values for (-)-malate, NAD+, and Mn2+ were 1.7, 0.16, and 0.15 mM, and 0.31, 0.06, and 0.09 mM, respectively. At pH 7.4 (5MM fumarate) and pH 6.0 (no fumarate), the Km values for (-)-malate, NADP+, and Mn2+ were 6.5, 0.62, and 0.59 mM, and 0.68. 0.12, and 0.31 mM, respectively. The apparent Ki values for ATP with NAD+ and NADP+ as coenzyme were 0.42 and 0.27 mM, respectively."}
{"id": "PMID:238990", "title": "The primary structure of actin from rabbit skeletal muscle. Three cyanogen bromide peptides that are insoluble at neutral pH.", "content": "Three of the 17 peptides produced when actin is treated with cyanogen bromide are sparingly soluble at pH values near neutrality. They were separated from more soluble peptides at pH 6.0 on a column of Sephadex G-10. The soluble peptides were excluded from the gel and emerged at the void volume, while the insoluble peptides were \"washed off\" by the formic acid in which the sample was applied. The three insoluble peptides were sequenced as a group by studying peptides generated by tryptic and chymotryptic digestion of the mixture, and peptic digestion of the partially resolved peptides. The three peptides are: CB-15 (residues 133 to 176), CB-16 (residues 325 to 354), and CB-17 (residues 191 to 227).", "contents": "The primary structure of actin from rabbit skeletal muscle. Three cyanogen bromide peptides that are insoluble at neutral pH. Three of the 17 peptides produced when actin is treated with cyanogen bromide are sparingly soluble at pH values near neutrality. They were separated from more soluble peptides at pH 6.0 on a column of Sephadex G-10. The soluble peptides were excluded from the gel and emerged at the void volume, while the insoluble peptides were \"washed off\" by the formic acid in which the sample was applied. The three insoluble peptides were sequenced as a group by studying peptides generated by tryptic and chymotryptic digestion of the mixture, and peptic digestion of the partially resolved peptides. The three peptides are: CB-15 (residues 133 to 176), CB-16 (residues 325 to 354), and CB-17 (residues 191 to 227)."}
{"id": "PMID:238991", "title": "Hemoglobins of the tadpole of the bullfrog, Rana catesbeiana. Structure and function of isolated components.", "content": "Four major components of the hemoglobin of the bullfrog tadpole, Rana catesbeiana, have been isolated and characterized structurally and functionally. These components fall into two clear functional classes. Components I and II have substantially higher affinities for oxygen than do components III and IV. Components I and II predominate in very young tadpoles and are largely replaced by components III and IV in older tadpoles. The data (Broyles, R.H., and Frieden, E. (1973) Nature New Biol. 241, 207-209) indicate that component I arises in the kidney and components III and IV in the liver. The synchrony of appearance and functional similarity o components I and II suggest that component II probably also arises in the kidney. Thus the development of the tadpole is associated with the successive proliferation of three distinct populations of red cells, first from the kidney, then from the liver, and finally, after metamorphosis, from bone marrow...", "contents": "Hemoglobins of the tadpole of the bullfrog, Rana catesbeiana. Structure and function of isolated components. Four major components of the hemoglobin of the bullfrog tadpole, Rana catesbeiana, have been isolated and characterized structurally and functionally. These components fall into two clear functional classes. Components I and II have substantially higher affinities for oxygen than do components III and IV. Components I and II predominate in very young tadpoles and are largely replaced by components III and IV in older tadpoles. The data (Broyles, R.H., and Frieden, E. (1973) Nature New Biol. 241, 207-209) indicate that component I arises in the kidney and components III and IV in the liver. The synchrony of appearance and functional similarity o components I and II suggest that component II probably also arises in the kidney. Thus the development of the tadpole is associated with the successive proliferation of three distinct populations of red cells, first from the kidney, then from the liver, and finally, after metamorphosis, from bone marrow..."}
{"id": "PMID:238992", "title": "Spectral properties of Co(II)- and Ni(II)-activated rabbit muscle pyruvate kinase.", "content": "Stoichiometry, kinetics, and optical properties of rabbit muscle pyruvate kinase activated with Co(II), Ni(II), Mg(II), and Mn(II) were studied. The stoichiometry of metal binding to enzyme was found to be 4 metal ions per tetrameric enzyme for Co(II) and Ni(II) by carrying out circular dichroic titrations. Cu(II) and Fe(II) were inactive. Ca(II) and Zn(II) were not activating, and were inhibitory with respect to all of the active cations. The temperature dependence of the optimal velocity is similar for all activating metals. The pH rate profiles suggest that there are two classes of enzyme activation by metal ions. Mg(II) and Mn(II) are quite similar to each other while Co(II) and Ni(II) are different from them but similar to each other. Absorption, natural, and magnetic CD in the visible region were used to probe the environment of the activating divalent cation in Ni(II)- and Co(II)-activated pyruvate kinase and their complexes with substrates and inhibitors...", "contents": "Spectral properties of Co(II)- and Ni(II)-activated rabbit muscle pyruvate kinase. Stoichiometry, kinetics, and optical properties of rabbit muscle pyruvate kinase activated with Co(II), Ni(II), Mg(II), and Mn(II) were studied. The stoichiometry of metal binding to enzyme was found to be 4 metal ions per tetrameric enzyme for Co(II) and Ni(II) by carrying out circular dichroic titrations. Cu(II) and Fe(II) were inactive. Ca(II) and Zn(II) were not activating, and were inhibitory with respect to all of the active cations. The temperature dependence of the optimal velocity is similar for all activating metals. The pH rate profiles suggest that there are two classes of enzyme activation by metal ions. Mg(II) and Mn(II) are quite similar to each other while Co(II) and Ni(II) are different from them but similar to each other. Absorption, natural, and magnetic CD in the visible region were used to probe the environment of the activating divalent cation in Ni(II)- and Co(II)-activated pyruvate kinase and their complexes with substrates and inhibitors..."}
{"id": "PMID:238993", "title": "Studies on indoleamine 2,3-dioxygenase. I. Superoxide anion as substrate.", "content": "Indoleamine 2,3-dioxygenase purified to apparent homogeneity from rabbit intestine was inhibited by scavengers for superoxide anion such as superoxide dismutase and 1,2-dihydroxybenzene-3,5-disulfonic acid (Tiron). On the other hand, beta-carotene and 1,4-diazobicyclo-(2,2,2)-octane, scavengers for singlet oxygen, did not affect the enzyme activity significantly. The degree of inhibition of the dioxygenase by superoxide dismutase preparations from bovine erythrocytes, green peas, spinach leaves, and Escherichia coli paralleled that observed with these dismutase preparations on the aerobic reduction of cytochrome c by xanthine oxidase and its substrate. The pH profiles of the inhibition by dismutase of the dioxygenase and cytochrome c reduction were also similar and the maximal inhibition was observed around pH 10 in both cases. The degree of inhibition was not affected by the concentration of substrate but was a function of the concentration of dismutase. It was inversely related to the concentrations of the dioxygenase and its cofactors, ascorbic acid and methylene blue, both of which were required for maximum activity. Ascorbic acid could be replaced either by xanthine oxidase and its substrate, or by tetrabutylammonium superoxide prepared by electrolytic reduction of molecular oxygen, or by potassium superoxide. When limited amounts of superoxide anion were added to the reaction mixture containing a substrate amount of the dioxygenase, the ratio of the amount of superoxide anion added to that of the product formed was approximately unity both under aerobic and anaerobic conditions. Taken together, these findings indicate that superoxide anion, rather than molecular oxygen, is utilized as substrate by indoleamine 2,3-dioxygenase.", "contents": "Studies on indoleamine 2,3-dioxygenase. I. Superoxide anion as substrate. Indoleamine 2,3-dioxygenase purified to apparent homogeneity from rabbit intestine was inhibited by scavengers for superoxide anion such as superoxide dismutase and 1,2-dihydroxybenzene-3,5-disulfonic acid (Tiron). On the other hand, beta-carotene and 1,4-diazobicyclo-(2,2,2)-octane, scavengers for singlet oxygen, did not affect the enzyme activity significantly. The degree of inhibition of the dioxygenase by superoxide dismutase preparations from bovine erythrocytes, green peas, spinach leaves, and Escherichia coli paralleled that observed with these dismutase preparations on the aerobic reduction of cytochrome c by xanthine oxidase and its substrate. The pH profiles of the inhibition by dismutase of the dioxygenase and cytochrome c reduction were also similar and the maximal inhibition was observed around pH 10 in both cases. The degree of inhibition was not affected by the concentration of substrate but was a function of the concentration of dismutase. It was inversely related to the concentrations of the dioxygenase and its cofactors, ascorbic acid and methylene blue, both of which were required for maximum activity. Ascorbic acid could be replaced either by xanthine oxidase and its substrate, or by tetrabutylammonium superoxide prepared by electrolytic reduction of molecular oxygen, or by potassium superoxide. When limited amounts of superoxide anion were added to the reaction mixture containing a substrate amount of the dioxygenase, the ratio of the amount of superoxide anion added to that of the product formed was approximately unity both under aerobic and anaerobic conditions. Taken together, these findings indicate that superoxide anion, rather than molecular oxygen, is utilized as substrate by indoleamine 2,3-dioxygenase."}
{"id": "PMID:238994", "title": "Bovine kidney alkaline phosphatase. Catalytic properties, subunit interactions in the catalytic process, and mechanism of Mg2+ stimulation.", "content": "Kidney alkaline phosphatase is an enzyme which requires two types of metals for maximal activity: zinc, which is essential, and magnesium, which is stimulatory. The main features of the Mg2+ stimulation have been analyzed. The stimulation is pH-dependent and is observed mainly between pH 7.5 and 10.5. Mg2+ binding to native alkaline phosphatase is characterized by a dissociation constant of 50 muM at pH 8.5,25 degrees. Binding of Zn2+ is an athermic process. Both the rate constants of association, ka, and of dissociation, kd, have low values. Typical values are 7 M(-1) at pH 8.0, 25 degrees, for ka and 4.10(-4) S(-1) at pH 8.0, 25 degrees, for kd. The on and off processes have high activation energies of 29 kcal mol (-1). Mg2+ can be replaced at its specific site by Mn2+, Co2+, Ni2+, and Zn2+. Zinc binding to the Mg2+ site inhibits the native alkaline phosphatase. Mn2+, Co2+, and Ni2+ also bind to the Mg2+ site with a stimulatory effect which is nearly identic-al with that of Mg2+, Mn2+ is the stimulatory cation which binds most tightly to the Mg2+ site; the dissociation constant of the Mn2+ kidney phosphatase complex is 2 muM at pH 8.5. The stoichiometry of Mn2+ binding has been found to be 1 eq of Mn2+ per mol of dimeric kidney phosphatase. The native enzyme displays absolute half-site reactivity for Mn2+ binding. Mg2+ binding site and the substrate binding sites are distinct sites. The Mg2+ stimulation corresponds to an allosteric effect. Mg2+ binding to its specific sites does not affect substrate recognition, it selectively affects Vmax values. Quenching of the phosphoenzyme formed under steady state conditions with [32P]AMP as a substrate as well as stopped flow analysis of the catalyzed hydrolysis of 2,4-dinitrophenyl phosphate or p-nitrophenyl phosphate have shown that the two active sites of the native and of the Mg2+-stimulated enzyme are not equivalent. Stopped flow analysis indicated that one of the two active sites was phosphorylated very rapidly whereas the other one was phosphorylated much more slowly at pH 4.2. Half of the sites were shown to be reactive at pH 8.0. Quenching experiments have shown that only one of the two sites is phosphorylated at any instant; this result was confirmed by the stopped flow observation of a burst of only 1 mol of nitrophenol per mol of dimeric phosphatase in the pre-steady state hydrolysis of p-nitrophenyl phosphate. The half-of-the-sites reactivity observed for the native and for the Mg2+-stimulated enzyme indicates that the same type of complex, the monophosphorylated complex, accumulates under steady state conditions with both types of enzymes. Mg2+ binding to the native enzyme at pH 8.0 increases considerably the dephosphorylation rate of this monophosphorylated intermediate. A possible mechanism of Mg2+ stimulation is discussed.", "contents": "Bovine kidney alkaline phosphatase. Catalytic properties, subunit interactions in the catalytic process, and mechanism of Mg2+ stimulation. Kidney alkaline phosphatase is an enzyme which requires two types of metals for maximal activity: zinc, which is essential, and magnesium, which is stimulatory. The main features of the Mg2+ stimulation have been analyzed. The stimulation is pH-dependent and is observed mainly between pH 7.5 and 10.5. Mg2+ binding to native alkaline phosphatase is characterized by a dissociation constant of 50 muM at pH 8.5,25 degrees. Binding of Zn2+ is an athermic process. Both the rate constants of association, ka, and of dissociation, kd, have low values. Typical values are 7 M(-1) at pH 8.0, 25 degrees, for ka and 4.10(-4) S(-1) at pH 8.0, 25 degrees, for kd. The on and off processes have high activation energies of 29 kcal mol (-1). Mg2+ can be replaced at its specific site by Mn2+, Co2+, Ni2+, and Zn2+. Zinc binding to the Mg2+ site inhibits the native alkaline phosphatase. Mn2+, Co2+, and Ni2+ also bind to the Mg2+ site with a stimulatory effect which is nearly identic-al with that of Mg2+, Mn2+ is the stimulatory cation which binds most tightly to the Mg2+ site; the dissociation constant of the Mn2+ kidney phosphatase complex is 2 muM at pH 8.5. The stoichiometry of Mn2+ binding has been found to be 1 eq of Mn2+ per mol of dimeric kidney phosphatase. The native enzyme displays absolute half-site reactivity for Mn2+ binding. Mg2+ binding site and the substrate binding sites are distinct sites. The Mg2+ stimulation corresponds to an allosteric effect. Mg2+ binding to its specific sites does not affect substrate recognition, it selectively affects Vmax values. Quenching of the phosphoenzyme formed under steady state conditions with [32P]AMP as a substrate as well as stopped flow analysis of the catalyzed hydrolysis of 2,4-dinitrophenyl phosphate or p-nitrophenyl phosphate have shown that the two active sites of the native and of the Mg2+-stimulated enzyme are not equivalent. Stopped flow analysis indicated that one of the two active sites was phosphorylated very rapidly whereas the other one was phosphorylated much more slowly at pH 4.2. Half of the sites were shown to be reactive at pH 8.0. Quenching experiments have shown that only one of the two sites is phosphorylated at any instant; this result was confirmed by the stopped flow observation of a burst of only 1 mol of nitrophenol per mol of dimeric phosphatase in the pre-steady state hydrolysis of p-nitrophenyl phosphate. The half-of-the-sites reactivity observed for the native and for the Mg2+-stimulated enzyme indicates that the same type of complex, the monophosphorylated complex, accumulates under steady state conditions with both types of enzymes. Mg2+ binding to the native enzyme at pH 8.0 increases considerably the dephosphorylation rate of this monophosphorylated intermediate. A possible mechanism of Mg2+ stimulation is discussed."}
{"id": "PMID:238995", "title": "Specific recognition of choline residues in the cell wall teichoic acid by the N-acetylmuramyl-L-alanine amidase of Pneumococcus.", "content": "Pneumococci growing on choline-containing medium are known to incorporate this amino alcohol into the wall teichoic acid and produce autolysin-sensitive cell walls. In contrast, bacteria grown on the choline analogue, ethanolamine, incorporate ethanolamine into the teichoic acid and synthesize cell walls that are resistant to the homologous autolysin. In this communication, we report experiments aimed at understanding the biochemical mechanism of this phenomenon. Ethanolamine-containing (autolysin-resistant) cell walls were methylated in vitro with methyl iodide. Under appropriate conditions, virtually all of the ethanolamine residues could be converted to choline. After methylation, the formerly autolysin-resistant walls could be quantitatively hydrolyzed by the pneumococcal autolysin. Methylated walls also recovered another property typical of cell walls isolated from choline-grown bacteria: they could induce the in vitro \"conversion\" of an inactive form of autolysin to the catalytically active form (Tomasz, A., and Westphal, M. (1971) Proc. Natl. Acad. Sci. U.S.A. 68, 2627-2630). The results suggest that the autolysin-catalyzed hydrolysis of amide bonds in the peptidoglycan requires an additional interaction between the enzyme protein and choline residues in the teichoric acid portion of the cell wall.", "contents": "Specific recognition of choline residues in the cell wall teichoic acid by the N-acetylmuramyl-L-alanine amidase of Pneumococcus. Pneumococci growing on choline-containing medium are known to incorporate this amino alcohol into the wall teichoic acid and produce autolysin-sensitive cell walls. In contrast, bacteria grown on the choline analogue, ethanolamine, incorporate ethanolamine into the teichoic acid and synthesize cell walls that are resistant to the homologous autolysin. In this communication, we report experiments aimed at understanding the biochemical mechanism of this phenomenon. Ethanolamine-containing (autolysin-resistant) cell walls were methylated in vitro with methyl iodide. Under appropriate conditions, virtually all of the ethanolamine residues could be converted to choline. After methylation, the formerly autolysin-resistant walls could be quantitatively hydrolyzed by the pneumococcal autolysin. Methylated walls also recovered another property typical of cell walls isolated from choline-grown bacteria: they could induce the in vitro \"conversion\" of an inactive form of autolysin to the catalytically active form (Tomasz, A., and Westphal, M. (1971) Proc. Natl. Acad. Sci. U.S.A. 68, 2627-2630). The results suggest that the autolysin-catalyzed hydrolysis of amide bonds in the peptidoglycan requires an additional interaction between the enzyme protein and choline residues in the teichoric acid portion of the cell wall."}
{"id": "PMID:238996", "title": "Purification and properties of an NADP-specific 6-phosphogluconate dehydrogenase from Streptococcus faecalis.", "content": "A procedure is described for the purification of 6-phosphogluconate dehydrogenase (6-phospho-D-gluconate:NADP oxidoreductase (decarboxylating) EC 1.1.1.44) from cell extracts of Streptococcus gaecalis. A 180-fold purification was achieved with an over-all yield of about 12% and an average specific activity of 14. The enzyme was homogeneous as determined by polyacrylamide gel electrophoresis, immunoelectrophoresis, and sedimentation equilibrium, studies. Its weight average molecular weight, as measured by sedimentation equilibrium, was 108,000 +/- 3,600. Other methods employed for molecular weight determinations gave values that ranged between 106,000 and 115,000. An analysis of the enzyme by sodium dodecyl sulfate polyacrylamide gel electrophoresis showed it to be a dimer composed of subunits having equal molecular weight. The amino acid composition of the streptococcal enzyme is reported. The apparent Km values for NADP and 6-phosphogluconate were calculated from kinetic data and found to be 0.015 mM and 0.024 mM, respectively. Kinetic studies also indicated that the binding of one substrate did not affect the apparent affinity of the enzyme for the other substrate.", "contents": "Purification and properties of an NADP-specific 6-phosphogluconate dehydrogenase from Streptococcus faecalis. A procedure is described for the purification of 6-phosphogluconate dehydrogenase (6-phospho-D-gluconate:NADP oxidoreductase (decarboxylating) EC 1.1.1.44) from cell extracts of Streptococcus gaecalis. A 180-fold purification was achieved with an over-all yield of about 12% and an average specific activity of 14. The enzyme was homogeneous as determined by polyacrylamide gel electrophoresis, immunoelectrophoresis, and sedimentation equilibrium, studies. Its weight average molecular weight, as measured by sedimentation equilibrium, was 108,000 +/- 3,600. Other methods employed for molecular weight determinations gave values that ranged between 106,000 and 115,000. An analysis of the enzyme by sodium dodecyl sulfate polyacrylamide gel electrophoresis showed it to be a dimer composed of subunits having equal molecular weight. The amino acid composition of the streptococcal enzyme is reported. The apparent Km values for NADP and 6-phosphogluconate were calculated from kinetic data and found to be 0.015 mM and 0.024 mM, respectively. Kinetic studies also indicated that the binding of one substrate did not affect the apparent affinity of the enzyme for the other substrate."}
{"id": "PMID:238997", "title": "Isolation and characterization of a manganese-containing superoxide dismutase from yeast.", "content": "The cyanide-insensitive superoxide dismutase of yeast has been shown to be localized in the mitochondrial matrix. This enzyme has been isolated in good yield from bakers' yeast. Its molecular weight is 96,000. It is a tetramer, being composed of four subunits of equal size. Exposure to sodium dodecyl sulfate at 100 degrees caused dissociation into dimers, while similar treatment but in the presence of 2-mercaptoethanol caused complete dissociation into monomers. This enzyme contains 1 atom of manganese per subunit and its absorption in the visible suggests Mn(III) in the resting enzyme. Ascorbate caused partial bleaching, presumably by reduction to Mn(II). The amino acid composition was determined. This enzyme has activity comparable to that of other previously reported superoxide dismutases and like the chicken mitochondrial and the bacterial enzymes, its rate of reaction with O2 falls as the pH is raised above 7.8. Crystals of high quality were easily prepared.", "contents": "Isolation and characterization of a manganese-containing superoxide dismutase from yeast. The cyanide-insensitive superoxide dismutase of yeast has been shown to be localized in the mitochondrial matrix. This enzyme has been isolated in good yield from bakers' yeast. Its molecular weight is 96,000. It is a tetramer, being composed of four subunits of equal size. Exposure to sodium dodecyl sulfate at 100 degrees caused dissociation into dimers, while similar treatment but in the presence of 2-mercaptoethanol caused complete dissociation into monomers. This enzyme contains 1 atom of manganese per subunit and its absorption in the visible suggests Mn(III) in the resting enzyme. Ascorbate caused partial bleaching, presumably by reduction to Mn(II). The amino acid composition was determined. This enzyme has activity comparable to that of other previously reported superoxide dismutases and like the chicken mitochondrial and the bacterial enzymes, its rate of reaction with O2 falls as the pH is raised above 7.8. Crystals of high quality were easily prepared."}
{"id": "PMID:238998", "title": "Experimental allergic aspermatogenic orchitis. 1. Isolation of a spermatozoal protein (AP1) which induces allergic aspermatogenic orchitis.", "content": "A unique highly soluble aspermatogenic protein (AP1) was isolated from guinea pig testes and was shown by immunofluorescence to occupy the outer surface of the sperm acrosome. This protein is a potent inducer of allergic orchitis and aspermatogenesis; as little as 0.2 mug induced orchitis in 60 percent of guinea pig tested. The AP1 protein, relatively small and neutral, is stable under acid conditions, but at pH 8.6 shows a variety of forms due either to aggregation or polymorphism. The purified AP1 protein appeared homogeneous by polyacrylamide gel electrophoresis at pH 2.7 and in sodium dodecyl sulfate and by immunoelectrophoresis using rabbit antisera to either the purified protein or the testes extract. It also showed a single band on immunodiffusion over a wide concentration range. The purification procedure consisted of delipidation with chloroform/methanol (2/1); acid extraction at pH 3.0; precipitation with 85 percent saturated ammonium sulfate; trichloroacetic acid extraction and gel filtration on Bio-Gel A-1.5; gel filtration on Bio-Gel P-10; chromatography on CM52 cellulose; and preparative gel electrophoresis at pH 2.7. Approximately 20 mg of purified AP1 protein were obtained from 5000 g of wet guinea pig testes. The AP1 protein induced an autoimmune disease characterized by infiltration of mononuclear cells around and within the seminiferous tubules (orchitis), followed by extensive damage and destruction of the germinal cells (aspermatogenesis). The course of the disease induced by this protein (0.5 to 1 mug) was essentially identical with that seen with whole testicular tissue or other purified fractions.", "contents": "Experimental allergic aspermatogenic orchitis. 1. Isolation of a spermatozoal protein (AP1) which induces allergic aspermatogenic orchitis. A unique highly soluble aspermatogenic protein (AP1) was isolated from guinea pig testes and was shown by immunofluorescence to occupy the outer surface of the sperm acrosome. This protein is a potent inducer of allergic orchitis and aspermatogenesis; as little as 0.2 mug induced orchitis in 60 percent of guinea pig tested. The AP1 protein, relatively small and neutral, is stable under acid conditions, but at pH 8.6 shows a variety of forms due either to aggregation or polymorphism. The purified AP1 protein appeared homogeneous by polyacrylamide gel electrophoresis at pH 2.7 and in sodium dodecyl sulfate and by immunoelectrophoresis using rabbit antisera to either the purified protein or the testes extract. It also showed a single band on immunodiffusion over a wide concentration range. The purification procedure consisted of delipidation with chloroform/methanol (2/1); acid extraction at pH 3.0; precipitation with 85 percent saturated ammonium sulfate; trichloroacetic acid extraction and gel filtration on Bio-Gel A-1.5; gel filtration on Bio-Gel P-10; chromatography on CM52 cellulose; and preparative gel electrophoresis at pH 2.7. Approximately 20 mg of purified AP1 protein were obtained from 5000 g of wet guinea pig testes. The AP1 protein induced an autoimmune disease characterized by infiltration of mononuclear cells around and within the seminiferous tubules (orchitis), followed by extensive damage and destruction of the germinal cells (aspermatogenesis). The course of the disease induced by this protein (0.5 to 1 mug) was essentially identical with that seen with whole testicular tissue or other purified fractions."}
{"id": "PMID:238999", "title": "Phosphoenolpyruvate hydrolase activity of rabbit muscle pyruvate kinase.", "content": "Rabbit muscle pyruvate kinase catalyzes the hydrolysis of P-enolpyruvate at the same active site which catalyzes the physiologically important kinase reaction. The hydrolase activity is lower than the kinase activity by a factor of at least 10(3). There are specific monovalent cation and divalent cation requirements. No other cofactors are required. The relative activation of the pyruvate kinase for the hydrolase reaction is: Ni(II) greater than Co(II) greater than Mg(II) greater than Mn(II). This parallels the rates of nonenzymatic hydrolysis of P-enolpyruvate (Benkovic, S.J., and Schray, K.J. (1968) Biochemistry 7, 4097-4102). The pH rate profiles of the hydrolase and kinase reactions activated by Ni(II) and Co(II) are similar, suggesting common features in their mechanisms. In contrast to the kinase reaction, the reaction velocity of the hydrolase increases at high Co(II) concentrations indicating a second mode for hydrolysis.", "contents": "Phosphoenolpyruvate hydrolase activity of rabbit muscle pyruvate kinase. Rabbit muscle pyruvate kinase catalyzes the hydrolysis of P-enolpyruvate at the same active site which catalyzes the physiologically important kinase reaction. The hydrolase activity is lower than the kinase activity by a factor of at least 10(3). There are specific monovalent cation and divalent cation requirements. No other cofactors are required. The relative activation of the pyruvate kinase for the hydrolase reaction is: Ni(II) greater than Co(II) greater than Mg(II) greater than Mn(II). This parallels the rates of nonenzymatic hydrolysis of P-enolpyruvate (Benkovic, S.J., and Schray, K.J. (1968) Biochemistry 7, 4097-4102). The pH rate profiles of the hydrolase and kinase reactions activated by Ni(II) and Co(II) are similar, suggesting common features in their mechanisms. In contrast to the kinase reaction, the reaction velocity of the hydrolase increases at high Co(II) concentrations indicating a second mode for hydrolysis."}
{"id": "PMID:239001", "title": "Resistance and tolerance of myocardium in ischemia: experimental results.", "content": "The resistance of the normal myocardium to ischemia can be determined by the metabolic and electric investigations, and particularly by the determination of the intra-myocardial potentials. The aspect of V.F. and the metabolic changes allow aetiologic deductions on the V.F. and are helpful for the treatment.", "contents": "Resistance and tolerance of myocardium in ischemia: experimental results. The resistance of the normal myocardium to ischemia can be determined by the metabolic and electric investigations, and particularly by the determination of the intra-myocardial potentials. The aspect of V.F. and the metabolic changes allow aetiologic deductions on the V.F. and are helpful for the treatment."}
{"id": "PMID:239003", "title": "Permeability of muscle capillaries to small heme-peptides. Evidence for the existence of patent transendothelial channels.", "content": "Two heme-peptides (HP) of about 20-A diameter (heme-undecapeptide [H11P], mol wt approximately 1900 and heme-octapeptide [H8P], mol wt approximately 1550), obtained by enzymic hydrolysis of cytochrome c, were sued as probe molecules in muscle capillaries (rat diaphragm). They were localized in situ by a perixidase reaction, enhanced by the addition of imidazole to the incubation medium. Chromatography of plasma samples showed that HPs circulate predominantly as monomers for the duration of the experiments and are bound by aldehyde fixatives to plasma proteins to the extent of approximately 50% (H8P) to approximately 95% (H11P). Both tracers cross the endothelium primarily via plasmalemmal vesicles which become progressively labeled (by reaction product) from the blood front to the tissue front of the endothelium, in three successive resolvable phases. By the end of each phase the extent of labeling reaches greater than 90% of the corresponding vesicle population. Labeled vesicles appear as either isolated units or chains which form patent channels across the endothelium. The patency of these channels was checked by specimen tilting and graphic analysis of their images. No evidence was found for early or preferential marking of the intercellular junctions and spaces by reaction product. It is concluded that the channels are the most likely candidate for structural equivalents of the small pores of the capillary wall since they are continuous, water-filled passages, and are provided with one or more strictures of less than 100 A. Their frequency remains to be established by future work.", "contents": "Permeability of muscle capillaries to small heme-peptides. Evidence for the existence of patent transendothelial channels. Two heme-peptides (HP) of about 20-A diameter (heme-undecapeptide [H11P], mol wt approximately 1900 and heme-octapeptide [H8P], mol wt approximately 1550), obtained by enzymic hydrolysis of cytochrome c, were sued as probe molecules in muscle capillaries (rat diaphragm). They were localized in situ by a perixidase reaction, enhanced by the addition of imidazole to the incubation medium. Chromatography of plasma samples showed that HPs circulate predominantly as monomers for the duration of the experiments and are bound by aldehyde fixatives to plasma proteins to the extent of approximately 50% (H8P) to approximately 95% (H11P). Both tracers cross the endothelium primarily via plasmalemmal vesicles which become progressively labeled (by reaction product) from the blood front to the tissue front of the endothelium, in three successive resolvable phases. By the end of each phase the extent of labeling reaches greater than 90% of the corresponding vesicle population. Labeled vesicles appear as either isolated units or chains which form patent channels across the endothelium. The patency of these channels was checked by specimen tilting and graphic analysis of their images. No evidence was found for early or preferential marking of the intercellular junctions and spaces by reaction product. It is concluded that the channels are the most likely candidate for structural equivalents of the small pores of the capillary wall since they are continuous, water-filled passages, and are provided with one or more strictures of less than 100 A. Their frequency remains to be established by future work."}
{"id": "PMID:239004", "title": "The pulse current pattern generated by developing fucoid eggs.", "content": "Using a newly developed extracellular vibrating electrode, we have made the first study of the spatial distribution of the growth currents around a single developing egg. This pattern was studied during the current pulses wihic traverse two-celled Pelvetia embryos. These pulses can be stimulated to occur with a periodicity of 70 min by mild acidification of the dea water medium. Current enters only at the growing rhizoid's tip while leaving both the base of the rhizoid cell and the whole outer membrane of the thallus cell. The field in front of the rhizoid cell falls off as the inverse cube of the distance from the rhizoid cell's center in the manner of a dipole field. The total inward and outward currents are equal, agreeing with theory. The current density at the rhizoid cell's base is twice that at the top of the thallus cell and this probably represents a change in the outer membrane's properties. There are no significant differences in the durrent density over the thallus cell. These results suggest a model in which the pulse current leaks in through newly opened channels in the growing tip and leaks out elsewhere due to the resultant fall in the membrane potential.", "contents": "The pulse current pattern generated by developing fucoid eggs. Using a newly developed extracellular vibrating electrode, we have made the first study of the spatial distribution of the growth currents around a single developing egg. This pattern was studied during the current pulses wihic traverse two-celled Pelvetia embryos. These pulses can be stimulated to occur with a periodicity of 70 min by mild acidification of the dea water medium. Current enters only at the growing rhizoid's tip while leaving both the base of the rhizoid cell and the whole outer membrane of the thallus cell. The field in front of the rhizoid cell falls off as the inverse cube of the distance from the rhizoid cell's center in the manner of a dipole field. The total inward and outward currents are equal, agreeing with theory. The current density at the rhizoid cell's base is twice that at the top of the thallus cell and this probably represents a change in the outer membrane's properties. There are no significant differences in the durrent density over the thallus cell. These results suggest a model in which the pulse current leaks in through newly opened channels in the growing tip and leaks out elsewhere due to the resultant fall in the membrane potential."}
{"id": "PMID:239005", "title": "Histone proteases of avian erythroid cells.", "content": "Protease activity associated with avian erythroid chromatin has been studied by gel electrophoresis of histones. Histone degradation is minimal at neutral pH, but is readily detected when chromatin is incubated at pH 3, and is evident to a lesser extent at pH 9. As a result of the pH 3 activity, the f1 and f2 chistones are preferentially degraded when the histone complement is DNA-bound, but these histones are relatively resistant to attack when present as free histone. The pH 3 activity reported here has properties similar to those of neutral histone proteases from other tissues, except that it is not inhibited by bisulphite. Added exogenous proteins are not degraded. The activity of avian erythroid histone protease decreases as maturation of the cells proceeds. Since we have previously shown that turnover of DNA-bound f2c histone occurs in reticulocytes and histone synthesis is absent in erythrocytes, it is possible that the histone protease described here may be involved in f2c histone turnover.", "contents": "Histone proteases of avian erythroid cells. Protease activity associated with avian erythroid chromatin has been studied by gel electrophoresis of histones. Histone degradation is minimal at neutral pH, but is readily detected when chromatin is incubated at pH 3, and is evident to a lesser extent at pH 9. As a result of the pH 3 activity, the f1 and f2 chistones are preferentially degraded when the histone complement is DNA-bound, but these histones are relatively resistant to attack when present as free histone. The pH 3 activity reported here has properties similar to those of neutral histone proteases from other tissues, except that it is not inhibited by bisulphite. Added exogenous proteins are not degraded. The activity of avian erythroid histone protease decreases as maturation of the cells proceeds. Since we have previously shown that turnover of DNA-bound f2c histone occurs in reticulocytes and histone synthesis is absent in erythrocytes, it is possible that the histone protease described here may be involved in f2c histone turnover."}
{"id": "PMID:239002", "title": "Myocardial resistance and tolerance to ischemia: physiological and biochemical basis.", "content": "This article is a short review of newer findings concerning the physiological and biochemical bases of the heart's tolerance to ischemia. The following themes are discussed. I. Energy-pool, energy-demand, and efficiency of anaerobic metabolism, the essential determinants of reanimation time and the heart's tolerance to ischemia. II. Experimental results of ischemic heart arrest and the heart arrest induced by a sodium-poor calcium-free, procaine-containing cardioplegic solution, developed by the author. III. Equivalents of function, metabolism and structure during the anaerobic period of the myocardium. IV. The myocardium's capability to recover in dependence on the metabolic state of ischemia and summary of the most important points of gaining a long time of tolerated ischemia. V. Survey and prospects.", "contents": "Myocardial resistance and tolerance to ischemia: physiological and biochemical basis. This article is a short review of newer findings concerning the physiological and biochemical bases of the heart's tolerance to ischemia. The following themes are discussed. I. Energy-pool, energy-demand, and efficiency of anaerobic metabolism, the essential determinants of reanimation time and the heart's tolerance to ischemia. II. Experimental results of ischemic heart arrest and the heart arrest induced by a sodium-poor calcium-free, procaine-containing cardioplegic solution, developed by the author. III. Equivalents of function, metabolism and structure during the anaerobic period of the myocardium. IV. The myocardium's capability to recover in dependence on the metabolic state of ischemia and summary of the most important points of gaining a long time of tolerated ischemia. V. Survey and prospects."}
{"id": "PMID:239006", "title": "Adhesion of red blood cells to charged interfaces between immiscible liquids. A new method.", "content": "We have devised a method of making a flat oil/water interface which remains flat on inversion. Cell adhesion to the interface can be observed microscopically. Glutaraldehyde-fixed human red blood cells adhere to the interface between physiological saline and hexadecane containing surface-active behenic acid at pH values below about 7-5. At high pH values, cells are prevented from adhering due to dissociation of the carboxyl groups of behenic acid oriented in the interface. The negative red cells are driven away electrostatically. Adherent and non-adherent cells remain on the aqueous side of the interface and do not appreciably deform it when adherent. Cells are electrostatically attracted to a similar interface containing positively charged octadecyltrimethylammonium ions. Cells also adhere to an interface containing octadecanol, which carries no charge. Underlying both electrostatic repulsion and attraction between red cells and oil/water interfaces is an attractive force which may be of electrodynamic (van der Waals) origin.", "contents": "Adhesion of red blood cells to charged interfaces between immiscible liquids. A new method. We have devised a method of making a flat oil/water interface which remains flat on inversion. Cell adhesion to the interface can be observed microscopically. Glutaraldehyde-fixed human red blood cells adhere to the interface between physiological saline and hexadecane containing surface-active behenic acid at pH values below about 7-5. At high pH values, cells are prevented from adhering due to dissociation of the carboxyl groups of behenic acid oriented in the interface. The negative red cells are driven away electrostatically. Adherent and non-adherent cells remain on the aqueous side of the interface and do not appreciably deform it when adherent. Cells are electrostatically attracted to a similar interface containing positively charged octadecyltrimethylammonium ions. Cells also adhere to an interface containing octadecanol, which carries no charge. Underlying both electrostatic repulsion and attraction between red cells and oil/water interfaces is an attractive force which may be of electrodynamic (van der Waals) origin."}
{"id": "PMID:239007", "title": "Comparative serum and urine analyses by dual-detector anion-exchange chromatography.", "content": "A high-pressure anion-exchange chromatographic system has been modified to provide measurement of large numbers of molecular constituents in serum and for direct comparison to similar measurement in urine. Operating parameters have been adopted which greatly extend the range of elution for strongly retained anionic constituents and limit resolution of early-eluting basic and neutral compounds which were of less interest in this study. Dual monitoring by UV absorption and fluorescence produced by cerate oxidation provides both sensitive and wide-ranging detection capability. Comparative serum and urine chromatograms for a clinically normal subject, a subject after ingesting the drug 4-hydroxyacetanilide, and an infant suffering from extreme acidosis, illustrate the potential usefulness of this analysis in studying the origin, transport, in vivo reactions, and disposition of metabolites.", "contents": "Comparative serum and urine analyses by dual-detector anion-exchange chromatography. A high-pressure anion-exchange chromatographic system has been modified to provide measurement of large numbers of molecular constituents in serum and for direct comparison to similar measurement in urine. Operating parameters have been adopted which greatly extend the range of elution for strongly retained anionic constituents and limit resolution of early-eluting basic and neutral compounds which were of less interest in this study. Dual monitoring by UV absorption and fluorescence produced by cerate oxidation provides both sensitive and wide-ranging detection capability. Comparative serum and urine chromatograms for a clinically normal subject, a subject after ingesting the drug 4-hydroxyacetanilide, and an infant suffering from extreme acidosis, illustrate the potential usefulness of this analysis in studying the origin, transport, in vivo reactions, and disposition of metabolites."}
{"id": "PMID:239008", "title": "Ligand-exchange chromatography of amino acids on nickel-Chelex 100.", "content": "A ligand-exchange chromatographic proceudre for the selective separation of amino acids from inorganic ions is presented. It was found that the binding of amino acids to the nickel-Chelex 100 resin is pH dependent. At pH 8.5-9.1, only the basic amino acids lysine, histidine and arginine are quantitatively attached to the complex, whereas at pH 11, other amino acids with the exception of aspartic acid and glutamic acid are also bound, although not quantitatively. All of the amino acids can be eluted from the complex with 3 M ammonia solution without the displacement of nickel ions from the complex. This method can be used for the removal of the basic amino acids from solutions in the presence of inorganic ions as well as other amino acids.", "contents": "Ligand-exchange chromatography of amino acids on nickel-Chelex 100. A ligand-exchange chromatographic proceudre for the selective separation of amino acids from inorganic ions is presented. It was found that the binding of amino acids to the nickel-Chelex 100 resin is pH dependent. At pH 8.5-9.1, only the basic amino acids lysine, histidine and arginine are quantitatively attached to the complex, whereas at pH 11, other amino acids with the exception of aspartic acid and glutamic acid are also bound, although not quantitatively. All of the amino acids can be eluted from the complex with 3 M ammonia solution without the displacement of nickel ions from the complex. This method can be used for the removal of the basic amino acids from solutions in the presence of inorganic ions as well as other amino acids."}
{"id": "PMID:239009", "title": "Evidence against the occurrence of artifacts due to carrier ampholyte-protein binding during isoelectric focusing.", "content": "The formation of irreversible complexes between carrier ampholyte components and proteins was investigated by gel filtration of mixtures of proteins and radioactively labelled ampholytes. Experiments were performed both with purified proteins (albumin, ferritin, beta-glucuronidase) and with a complex mixture of proteins (serum); in no case was binding of ampholytes to proteins detected. Thus the results argue against the occurrence in isoelectric focusing of proteins of artifacts due to such complex formation.", "contents": "Evidence against the occurrence of artifacts due to carrier ampholyte-protein binding during isoelectric focusing. The formation of irreversible complexes between carrier ampholyte components and proteins was investigated by gel filtration of mixtures of proteins and radioactively labelled ampholytes. Experiments were performed both with purified proteins (albumin, ferritin, beta-glucuronidase) and with a complex mixture of proteins (serum); in no case was binding of ampholytes to proteins detected. Thus the results argue against the occurrence in isoelectric focusing of proteins of artifacts due to such complex formation."}
{"id": "PMID:239010", "title": "Rapid and sensitive gas chromatographic determination of diacetylmorphine and its metabolite monoacetylmorphine in blood using a nitrogen detector.", "content": "A quantitative gas chromatographic method for the determination of plasma concentrations of diacetylmorphine and its metabolite monacetylmorphine using an alkali flane detector (nitrogen detector) is described. Plasma samples (pH 9.0) containing ethylmorphine acetate as internal standard are extracted with benzene. The dried benzene extracts are analysed as their corresponding acetylated derivatives following treatment with trifluoroacetic anhydride-benzent (1:5). The nitrogen detector permits quantitation of narcotic levels down to 100ng/ml with detection as low as 20 ng/ml. The higher sensitivity and selectivity of the nitrogen detector are compared to those obtained in flame ionization detection. Species differences in the rate of conversion of diacetylmorphine to monacetylmorphine in vitro in blood are also presented.", "contents": "Rapid and sensitive gas chromatographic determination of diacetylmorphine and its metabolite monoacetylmorphine in blood using a nitrogen detector. A quantitative gas chromatographic method for the determination of plasma concentrations of diacetylmorphine and its metabolite monacetylmorphine using an alkali flane detector (nitrogen detector) is described. Plasma samples (pH 9.0) containing ethylmorphine acetate as internal standard are extracted with benzene. The dried benzene extracts are analysed as their corresponding acetylated derivatives following treatment with trifluoroacetic anhydride-benzent (1:5). The nitrogen detector permits quantitation of narcotic levels down to 100ng/ml with detection as low as 20 ng/ml. The higher sensitivity and selectivity of the nitrogen detector are compared to those obtained in flame ionization detection. Species differences in the rate of conversion of diacetylmorphine to monacetylmorphine in vitro in blood are also presented."}
{"id": "PMID:239013", "title": "Interaction of amino acids, N-acetyl amino acid esters, thymine and adenine with sephadex LH-20 gel.", "content": "N-Acetyl aromatic amino acid esters, tryptophan, adenine and thymine show strong retention in Sephadex LH-20 gel in an aqueous phase. The decreased retention in 6 M urea, the absence of retention in absolute methanol and the increased retention at higher temperatures in the aqueous phase indicate that hydrophobic interaction is responsible for the observed retention of the amino acids and their esters in the gel. Adenine was found to be retained by polar interaction in the gel. The increased retention of the solutes in the presence of different electrolytes suggests that the lyotropic effect is more important than the ionic strength effect. The relevance of the results obtained with amino acids and esters to the conformational aspects of proteins in aqueous solution is discussed.", "contents": "Interaction of amino acids, N-acetyl amino acid esters, thymine and adenine with sephadex LH-20 gel. N-Acetyl aromatic amino acid esters, tryptophan, adenine and thymine show strong retention in Sephadex LH-20 gel in an aqueous phase. The decreased retention in 6 M urea, the absence of retention in absolute methanol and the increased retention at higher temperatures in the aqueous phase indicate that hydrophobic interaction is responsible for the observed retention of the amino acids and their esters in the gel. Adenine was found to be retained by polar interaction in the gel. The increased retention of the solutes in the presence of different electrolytes suggests that the lyotropic effect is more important than the ionic strength effect. The relevance of the results obtained with amino acids and esters to the conformational aspects of proteins in aqueous solution is discussed."}
{"id": "PMID:239014", "title": "Quantitative determination of p-chlorophenoxyisobutyric acid in blood plasma by gas-liquid chromatography.", "content": "A gas-liquid chromatographic method for the determination of p-chlorophenoxyisobutyric (CPIB) acid in blood plasma is described. The substance is extracted from acidified plasma into benzene, the extract is evaporated to dryness and the residue is methylated with an alcohol-free solution of diazomethane and submitted to chromatography on a glass column packed with 3% OV-17. Data on the recovery, reproducibility and sensitivity of the method are given. CPIB acid plasma levels in rats after acute and prolonged treatments with the aluminium salt of CPIB acid (Atherolip) are also presented.", "contents": "Quantitative determination of p-chlorophenoxyisobutyric acid in blood plasma by gas-liquid chromatography. A gas-liquid chromatographic method for the determination of p-chlorophenoxyisobutyric (CPIB) acid in blood plasma is described. The substance is extracted from acidified plasma into benzene, the extract is evaporated to dryness and the residue is methylated with an alcohol-free solution of diazomethane and submitted to chromatography on a glass column packed with 3% OV-17. Data on the recovery, reproducibility and sensitivity of the method are given. CPIB acid plasma levels in rats after acute and prolonged treatments with the aluminium salt of CPIB acid (Atherolip) are also presented."}
{"id": "PMID:239016", "title": "Scanning isoelectric focusing in small density-gradient columns. IV. The use of deuterium oxide for preparing the density gradient and its effects on isoelectric points of proteins.", "content": "The use of deuterium oxide as a substitute for sucrose in preparing density gradients for small isoelectrofocusing columns has been investigated. A density gradient was created directly in a 1.5-ml column by free inter-diffusion of three deuterium oxide solutions for 3 min. The resulting deuterium oxide concentration course (as shown by measurement of the refractive-index gradient) had a very high degree of linearity. Test runs with beta-lactoglobulin and sperm-whale myoglobin showed that the strength and stability of the deuterium oxide density gradient should normally be sufficient for stabilization of protein zones against convection during isoelectric focusing. The isoelectric points of beta-lactoglobulins A and B were found to increase as the concentration ratio of deuterium oxide to water at focusing level increased. Within the limits of experimental error, the pI shift corresponding to a given change in solvent composition was equal for both components. These findings are accounted for in terms of the deuterium isotope effect on the dissociation constants of protolytic groups and the shift in the asymmetry potential of the glass electrode in deuterium oxide as compared with water. The spontaneous reduction of sperm-whale metmyoglobin to ferrous myoglobin, which occurs on prolonged isoelectric focusing, is discussed, as are the benefits and drawbacks of deuterium oxide as a density-gradient solute.", "contents": "Scanning isoelectric focusing in small density-gradient columns. IV. The use of deuterium oxide for preparing the density gradient and its effects on isoelectric points of proteins. The use of deuterium oxide as a substitute for sucrose in preparing density gradients for small isoelectrofocusing columns has been investigated. A density gradient was created directly in a 1.5-ml column by free inter-diffusion of three deuterium oxide solutions for 3 min. The resulting deuterium oxide concentration course (as shown by measurement of the refractive-index gradient) had a very high degree of linearity. Test runs with beta-lactoglobulin and sperm-whale myoglobin showed that the strength and stability of the deuterium oxide density gradient should normally be sufficient for stabilization of protein zones against convection during isoelectric focusing. The isoelectric points of beta-lactoglobulins A and B were found to increase as the concentration ratio of deuterium oxide to water at focusing level increased. Within the limits of experimental error, the pI shift corresponding to a given change in solvent composition was equal for both components. These findings are accounted for in terms of the deuterium isotope effect on the dissociation constants of protolytic groups and the shift in the asymmetry potential of the glass electrode in deuterium oxide as compared with water. The spontaneous reduction of sperm-whale metmyoglobin to ferrous myoglobin, which occurs on prolonged isoelectric focusing, is discussed, as are the benefits and drawbacks of deuterium oxide as a density-gradient solute."}
{"id": "PMID:239017", "title": "Rapid determination of selenium in various substrates by electron capture gas-liquid chromatography.", "content": "In the proposed procedure for the determination of selenium, 0.5-1 g of sample is wet ashed with concentrated nitric acid. After adding 1,2-diamino-4,5-dichlorobenzene to the digest at pH 1, the resulting dichloropiazselenol derivatives is extracted with toluene. The extract is purified by column chromatography over Florisil and analyzed by gas-liquid chromatography with electron capture detection. Recoveries of selenium added to various substrates ranged from 72 to 102%. The limit of detection is approximately 0.01 ppm, but smaller amounts can be determined by increasing the sample size or by concentration of the final extract.", "contents": "Rapid determination of selenium in various substrates by electron capture gas-liquid chromatography. In the proposed procedure for the determination of selenium, 0.5-1 g of sample is wet ashed with concentrated nitric acid. After adding 1,2-diamino-4,5-dichlorobenzene to the digest at pH 1, the resulting dichloropiazselenol derivatives is extracted with toluene. The extract is purified by column chromatography over Florisil and analyzed by gas-liquid chromatography with electron capture detection. Recoveries of selenium added to various substrates ranged from 72 to 102%. The limit of detection is approximately 0.01 ppm, but smaller amounts can be determined by increasing the sample size or by concentration of the final extract."}
{"id": "PMID:239018", "title": "Characterization of synthetic carrier ampholytes for isoelectric focusing.", "content": "The synthesis of carrier ampholytes suitable for isoelectric focusing is described. The mixture of hexamethylenetetramine (HMTA), triethylenetetramine (TETA), tetraethylenepentamine (TEPA) and pentaethylenehexamine (PEHA) ampholytes closely resembles commercial Ampholine, and covers the pH range 3-9.5. We have been able to detect focused ampholytes in a gel slab, taking advantage of their different refractive indices, and to assess their relative amounts along the pH gradient. PEHA ampholytes contain up to 20% of chromophoric structures, with two UV peaks at 368 and 315 nm, in a pH-dependent equilibrium, associated with a very weak nitrogen function having a pK of 1.1. This could be the pK6 of the last amino group in PEHA. However, NMR spectra failed to reveal any nitrogen heterocyclic structure formed during the synthesis. This mixture of ampholytes exhibits good conductivity, produces smooth pH gradients and allows sharp protein separations in the pH range 3-9.5. Their synthesis is very easy and their cost is extremely low. Their availability sould make feasible large-scale preparative isoelectric focusing, and attract more interest to continuous-flow techniques, where large amounts of ampholytes are required.", "contents": "Characterization of synthetic carrier ampholytes for isoelectric focusing. The synthesis of carrier ampholytes suitable for isoelectric focusing is described. The mixture of hexamethylenetetramine (HMTA), triethylenetetramine (TETA), tetraethylenepentamine (TEPA) and pentaethylenehexamine (PEHA) ampholytes closely resembles commercial Ampholine, and covers the pH range 3-9.5. We have been able to detect focused ampholytes in a gel slab, taking advantage of their different refractive indices, and to assess their relative amounts along the pH gradient. PEHA ampholytes contain up to 20% of chromophoric structures, with two UV peaks at 368 and 315 nm, in a pH-dependent equilibrium, associated with a very weak nitrogen function having a pK of 1.1. This could be the pK6 of the last amino group in PEHA. However, NMR spectra failed to reveal any nitrogen heterocyclic structure formed during the synthesis. This mixture of ampholytes exhibits good conductivity, produces smooth pH gradients and allows sharp protein separations in the pH range 3-9.5. Their synthesis is very easy and their cost is extremely low. Their availability sould make feasible large-scale preparative isoelectric focusing, and attract more interest to continuous-flow techniques, where large amounts of ampholytes are required."}
{"id": "PMID:239019", "title": "Fractionation of carrier ampholytes for isoelectric focusing.", "content": "A simple method for fractionating synthetic carrier ampholytes is reported, based on the principle of continuous-flow isoelectric focusing in gel-stabilized layers. An 8% ampholyte solution, encompassing the pH range 3-9.5, is separated into 12 fractions in a chamber filled with Sephadex G-100 by a continuous-flow technique. We are thus able to obtain ampholytes of narrow pH range, encompassing approximately 2 pH units, whose resolving power is comparable with that obtained with commercial Ampholine covering similar pH ranges.", "contents": "Fractionation of carrier ampholytes for isoelectric focusing. A simple method for fractionating synthetic carrier ampholytes is reported, based on the principle of continuous-flow isoelectric focusing in gel-stabilized layers. An 8% ampholyte solution, encompassing the pH range 3-9.5, is separated into 12 fractions in a chamber filled with Sephadex G-100 by a continuous-flow technique. We are thus able to obtain ampholytes of narrow pH range, encompassing approximately 2 pH units, whose resolving power is comparable with that obtained with commercial Ampholine covering similar pH ranges."}
{"id": "PMID:239020", "title": "Chromatographic behaviour of phenols on thin layers of cation and anion exchangers. II. Dowex 50-X4 and Rexyn 102.", "content": "The chromatographic characteristics of 58 phenols on Rexyn 102 and Dowex 50-X4 thin layers in both the acidic and sodium salt forms have been studied, using elution with water, water-alcohol mixtures and aqueous salt solutions at different pH values. The influence of the percentage of alcohol, the pH and the ionic strength on the chromatographic behaviour of these phenols was investigated. The validity of the relationships among the RF values, the pH of the eluent and the pKa of the phenol has been verified on Dowex 50-X4 (Na+) thin layers. It has been shown that from the RFac, RFalk and pKa values of the different phenols, it is possible to predict their behaviour over the whole pH range and therefore to select the best conditions for their chromatographic separation.", "contents": "Chromatographic behaviour of phenols on thin layers of cation and anion exchangers. II. Dowex 50-X4 and Rexyn 102. The chromatographic characteristics of 58 phenols on Rexyn 102 and Dowex 50-X4 thin layers in both the acidic and sodium salt forms have been studied, using elution with water, water-alcohol mixtures and aqueous salt solutions at different pH values. The influence of the percentage of alcohol, the pH and the ionic strength on the chromatographic behaviour of these phenols was investigated. The validity of the relationships among the RF values, the pH of the eluent and the pKa of the phenol has been verified on Dowex 50-X4 (Na+) thin layers. It has been shown that from the RFac, RFalk and pKa values of the different phenols, it is possible to predict their behaviour over the whole pH range and therefore to select the best conditions for their chromatographic separation."}
{"id": "PMID:239021", "title": "The standardisation of thin-layer chromatographic systems for the identification of basic drugs.", "content": "Three thin-layer chromatographic systems have been selected on the basis of their discriminating power on which to standardise for the identification of basic drugs. They are systems of silica gel sprayed with 0.1 N NaOH, dried and run using one of the following solvents: cyclohexane-toluene-diethylamine (75:15:10), chloroform-methanol (90:10) or acetone. They can be used in combination since their correlation coefficients are low. Four reference compounds should be used, equally spaced across the plate. The inter-laboratory variation of measurement of RF values has been ascertained and the use of a graphical RF correction method reduced the mean deviation of measurement to 0.02. The measurement of RF values was found to be less reproducible in the middle of the chromatogram than in regions of very low or very high RF values.", "contents": "The standardisation of thin-layer chromatographic systems for the identification of basic drugs. Three thin-layer chromatographic systems have been selected on the basis of their discriminating power on which to standardise for the identification of basic drugs. They are systems of silica gel sprayed with 0.1 N NaOH, dried and run using one of the following solvents: cyclohexane-toluene-diethylamine (75:15:10), chloroform-methanol (90:10) or acetone. They can be used in combination since their correlation coefficients are low. Four reference compounds should be used, equally spaced across the plate. The inter-laboratory variation of measurement of RF values has been ascertained and the use of a graphical RF correction method reduced the mean deviation of measurement to 0.02. The measurement of RF values was found to be less reproducible in the middle of the chromatogram than in regions of very low or very high RF values."}
{"id": "PMID:239022", "title": "Effect of volume expansion on renal citrate and ammonia metabolism in KCl-deficient rats.", "content": "When rats with desoxycorticosterone acetate (DOCA)-induced potassium chloride deficiency are given sodium chloride there is simultaneously a partial correction of metabolic alkalosis and a marked reduction in urinary citrate excretion and renal citrate content. To examine DOCA's role in this phenomenon and to determine how sodium chloride alters renal metabolism, rats were made KC1 deficient using furosemide and a KC1-deficient diet. Renal citrate and ammonia metabolism were then studied after chronic oral sodium chloride administration or acute volume expansion with isotonic mannitol. Although both maneuvers partially corrected metabolic alkalosis, sodium chloride raised serum chloride concentration while mannitol significantly decreased it. Urinary citrate excretion decreased to 10% of control in rats given NaCl and to 50% of control in rats infused with mannitol. The filtered load of citrate was constant or increased indicating increased tubular citrate reabsorption. Renal cortical citrate content also decreased approximately 50%. Renal cortical slices from KCl-deficient rats incubated in low or normal chloride media produced equal amounts of 14CO2 from (1, 5-14C) citrate. In addition, urinary ammonia excretion increased by over 300% in both groups. This occurred in the mannitol group despite increased urinary pH and flow rate indicating a rise in renal ammonia production. It seems that neither DOCA nor an increase in serum chloride concentration explains the experimental results. Rather, it appears that volume expansion is responsible for increased renal tubular citrate reabsorption and renal ammonia production. As these renal metabolic responses ordinarily occur in response to acidosis, the data are consistent with the hypothesis that volume expansion reduces renal cell pH in 3KCl-deficient rats.", "contents": "Effect of volume expansion on renal citrate and ammonia metabolism in KCl-deficient rats. When rats with desoxycorticosterone acetate (DOCA)-induced potassium chloride deficiency are given sodium chloride there is simultaneously a partial correction of metabolic alkalosis and a marked reduction in urinary citrate excretion and renal citrate content. To examine DOCA's role in this phenomenon and to determine how sodium chloride alters renal metabolism, rats were made KC1 deficient using furosemide and a KC1-deficient diet. Renal citrate and ammonia metabolism were then studied after chronic oral sodium chloride administration or acute volume expansion with isotonic mannitol. Although both maneuvers partially corrected metabolic alkalosis, sodium chloride raised serum chloride concentration while mannitol significantly decreased it. Urinary citrate excretion decreased to 10% of control in rats given NaCl and to 50% of control in rats infused with mannitol. The filtered load of citrate was constant or increased indicating increased tubular citrate reabsorption. Renal cortical citrate content also decreased approximately 50%. Renal cortical slices from KCl-deficient rats incubated in low or normal chloride media produced equal amounts of 14CO2 from (1, 5-14C) citrate. In addition, urinary ammonia excretion increased by over 300% in both groups. This occurred in the mannitol group despite increased urinary pH and flow rate indicating a rise in renal ammonia production. It seems that neither DOCA nor an increase in serum chloride concentration explains the experimental results. Rather, it appears that volume expansion is responsible for increased renal tubular citrate reabsorption and renal ammonia production. As these renal metabolic responses ordinarily occur in response to acidosis, the data are consistent with the hypothesis that volume expansion reduces renal cell pH in 3KCl-deficient rats."}
{"id": "PMID:239023", "title": "Serum enzyme levels in alcoholism and drug dependency.", "content": "Serum gamma glutamyl transpeptidase (GGTP), isocitrate dehydrogenase (ICD), ornithine carbamoyl transferase (OCT), alanine aminotransferase (AlT), aspartate aminotransferase (AsT), and alkaline phosphatase (ALP) activities were assayed in 67 alcoholics and 40 drug dependent patients. Bilirubin, total protein, albumin, and globulin were also measured. GGTP elevation was observed in 48% of alcoholics and in 50% of drug dependents. The incidences of elevated levels of other enzymes were: ICD 39 and 38-7%; OCT 23-7 and 36-1%; AlT 30 and 33%; AsT 24-2 and 21-7%; ALP 10-4 and 5% respectively. Measurement of GGTP is thus more useful as a screening test for involvement of the liver in alcoholics and drug dependent patients than that of the other enzymes.", "contents": "Serum enzyme levels in alcoholism and drug dependency. Serum gamma glutamyl transpeptidase (GGTP), isocitrate dehydrogenase (ICD), ornithine carbamoyl transferase (OCT), alanine aminotransferase (AlT), aspartate aminotransferase (AsT), and alkaline phosphatase (ALP) activities were assayed in 67 alcoholics and 40 drug dependent patients. Bilirubin, total protein, albumin, and globulin were also measured. GGTP elevation was observed in 48% of alcoholics and in 50% of drug dependents. The incidences of elevated levels of other enzymes were: ICD 39 and 38-7%; OCT 23-7 and 36-1%; AlT 30 and 33%; AsT 24-2 and 21-7%; ALP 10-4 and 5% respectively. Measurement of GGTP is thus more useful as a screening test for involvement of the liver in alcoholics and drug dependent patients than that of the other enzymes."}
{"id": "PMID:239024", "title": "The concentration of cerebrospinal fluid potassium during systemic disturbances of acid-base metabolism.", "content": "A possible relationship between blood acid-base state and the concentration of cerebrospinal fluid potassium has been examined in patients with systemic disturbances of acid-base metabolism. Over the range of values studied it was not possible to demonstrate any significant correlation between these parameters.", "contents": "The concentration of cerebrospinal fluid potassium during systemic disturbances of acid-base metabolism. A possible relationship between blood acid-base state and the concentration of cerebrospinal fluid potassium has been examined in patients with systemic disturbances of acid-base metabolism. Over the range of values studied it was not possible to demonstrate any significant correlation between these parameters."}
{"id": "PMID:239027", "title": "Combination drug therapy in psychopharmacology.", "content": "The frequency with which a psychotropic agent is used in combination with another drug preparation is emphasized. The authors present an update of the clinical and theoretical knowledge bearing on combination drug therapy in psychopharmacology. Drug combination interactions that enhance clinical efficacy and those that either diminish it or even endanger the patient are described. The authors hope to create an awareness on the part of physicians of the importance of being knowledgeable in the area of combination drug therapy. Any unexpected or unusual drug action should be examined for the possibility of a drug combination interaction.", "contents": "Combination drug therapy in psychopharmacology. The frequency with which a psychotropic agent is used in combination with another drug preparation is emphasized. The authors present an update of the clinical and theoretical knowledge bearing on combination drug therapy in psychopharmacology. Drug combination interactions that enhance clinical efficacy and those that either diminish it or even endanger the patient are described. The authors hope to create an awareness on the part of physicians of the importance of being knowledgeable in the area of combination drug therapy. Any unexpected or unusual drug action should be examined for the possibility of a drug combination interaction."}
{"id": "PMID:239028", "title": "Human brain in tissue culture. I. Acquisition, initial processing, and establishment of brain cell cultures.", "content": "This paper details the in vitro techniques used to establish cells in culture from the brains of 40 patients, most of whom had chronic neurologic disease. The clinical and pathologic features of these patients are given. The success in establihsing cell lines was dependent upon the origin of tissue (biopsy vs. autopsy), the site of removal from the brain, and various environmental and technical manipulations in vitro.", "contents": "Human brain in tissue culture. I. Acquisition, initial processing, and establishment of brain cell cultures. This paper details the in vitro techniques used to establish cells in culture from the brains of 40 patients, most of whom had chronic neurologic disease. The clinical and pathologic features of these patients are given. The success in establihsing cell lines was dependent upon the origin of tissue (biopsy vs. autopsy), the site of removal from the brain, and various environmental and technical manipulations in vitro."}
{"id": "PMID:239029", "title": "Human brain in tissue culture. II. Studies of long-term cultures.", "content": "This paper describes the techniques used to maintain and reconstitute from storage adult human brain cells in culture. Growth characteristics, cell morphology, lifespan, and karyotypic analysis of cell lines derived from patients with multiple sclerosis (MS), non-MS neurologic diseases, and normal brains are compared.", "contents": "Human brain in tissue culture. II. Studies of long-term cultures. This paper describes the techniques used to maintain and reconstitute from storage adult human brain cells in culture. Growth characteristics, cell morphology, lifespan, and karyotypic analysis of cell lines derived from patients with multiple sclerosis (MS), non-MS neurologic diseases, and normal brains are compared."}
{"id": "PMID:239030", "title": "Mode of distribution of aminergic fibers in the cerebellar cortex of the chicken.", "content": "The cerebellar cortex of adult hens contains a dense plexus of thin varicose nerve fibers which display a formaldehyde-induced green fluorescence. This plexus is not distributed at random in the cortical layers. Within the granular layer the plexus forms a netlike pattern. The fiber branches, which have numerous varicosities, are predominantly oriented in the traverse plane of the folium. In the molecular layer the fluorescent plexus shows some variations in the convex, flat and concave portions of the folia. Many of the fluorescent branches are oriented parallel to the course of the folium. They arise from a T-division of radially oriented axons resembling parallel fibers in Golgi sections. The meshes of the fluorescent plexus in the granular layer measure 10-60 mu. In the molecular layer (top of the folia) there are about 30 fluorescent fibers per 100 mu2. The fluorescent fibers originate from the locus coeruleus and form a rostral and a caudal bundle in the cerebellar peduncle. The mode of distribution of the fluorescent fibers in the cortical layers seems to depend on the organization of the innervated tissue. Light microscopy suggests that the aminergic fibers innervate more than one class of cerebellar neurons.", "contents": "Mode of distribution of aminergic fibers in the cerebellar cortex of the chicken. The cerebellar cortex of adult hens contains a dense plexus of thin varicose nerve fibers which display a formaldehyde-induced green fluorescence. This plexus is not distributed at random in the cortical layers. Within the granular layer the plexus forms a netlike pattern. The fiber branches, which have numerous varicosities, are predominantly oriented in the traverse plane of the folium. In the molecular layer the fluorescent plexus shows some variations in the convex, flat and concave portions of the folia. Many of the fluorescent branches are oriented parallel to the course of the folium. They arise from a T-division of radially oriented axons resembling parallel fibers in Golgi sections. The meshes of the fluorescent plexus in the granular layer measure 10-60 mu. In the molecular layer (top of the folia) there are about 30 fluorescent fibers per 100 mu2. The fluorescent fibers originate from the locus coeruleus and form a rostral and a caudal bundle in the cerebellar peduncle. The mode of distribution of the fluorescent fibers in the cortical layers seems to depend on the organization of the innervated tissue. Light microscopy suggests that the aminergic fibers innervate more than one class of cerebellar neurons."}
{"id": "PMID:239031", "title": "Neurochemical regulation of feeding in the rat: facilitation by alpha-noradrenergic, but not dopaminergic, receptor stimulants.", "content": "Rats ate voraciously after intraventricular injections of the alpha-noradrenergic receptor stimulant clonidine. Intraventricular administration of l-norepinephrine also facilitated feeding, but similar injections of dopamine and apomorphine (a dopamine receptor stimulant) were ineffective and even tended to suppress feeding. Clonidine was 100 times more potent than norepinephrine and increased the intake of both the ordinary diet of powdered food and a highly palatable wet food. The anorexic action of amphetamine was reversed by centrally administered clonidine. These observations suggest \"respondent\" rather than \"operant\" regulation of feeding by noradrenergic systems. That is, in relation to noradrenergic mechanisms, feeding appears to be a respondent which is sensitized or disinhibited by activation of alpha-noradrenergic receptors, rather than an operant which is reinforced by the release of norepinephrine.", "contents": "Neurochemical regulation of feeding in the rat: facilitation by alpha-noradrenergic, but not dopaminergic, receptor stimulants. Rats ate voraciously after intraventricular injections of the alpha-noradrenergic receptor stimulant clonidine. Intraventricular administration of l-norepinephrine also facilitated feeding, but similar injections of dopamine and apomorphine (a dopamine receptor stimulant) were ineffective and even tended to suppress feeding. Clonidine was 100 times more potent than norepinephrine and increased the intake of both the ordinary diet of powdered food and a highly palatable wet food. The anorexic action of amphetamine was reversed by centrally administered clonidine. These observations suggest \"respondent\" rather than \"operant\" regulation of feeding by noradrenergic systems. That is, in relation to noradrenergic mechanisms, feeding appears to be a respondent which is sensitized or disinhibited by activation of alpha-noradrenergic receptors, rather than an operant which is reinforced by the release of norepinephrine."}
{"id": "PMID:239032", "title": "Comparison of behaviors elicited by electrical brain stimulation in dorsal brain stem and hypothalamus of rats.", "content": "Four brain-stimulation phenomena elicited from both dorsal brain stem and hypothalamic sites were investigated with the following results:  (a) intracranial self-stimulation rate-intensity functions for dorsal brain stem and hypothalamic sites yielded very high (over 1,000 responses/15 min.) to moderate (201-500 responses/15 min.) response rates; (b) d-amphetamine produced higher response rates than either l-amphetamine or saline at both dorsal brain stem and hypothalamic sites, indicating that noradrenergic dorsal brain stem fibers (or cell bodies) support intracranial self-stimulation; (c) dorsal brain stem and hypothalamic self-stimulation sites reliably produced escape behavior; (d) simultaneous stimulation of dorsal brain stem and hypothalamic sites at subthreshold intensities interacted to produce suprathreshold response rates.", "contents": "Comparison of behaviors elicited by electrical brain stimulation in dorsal brain stem and hypothalamus of rats. Four brain-stimulation phenomena elicited from both dorsal brain stem and hypothalamic sites were investigated with the following results:  (a) intracranial self-stimulation rate-intensity functions for dorsal brain stem and hypothalamic sites yielded very high (over 1,000 responses/15 min.) to moderate (201-500 responses/15 min.) response rates; (b) d-amphetamine produced higher response rates than either l-amphetamine or saline at both dorsal brain stem and hypothalamic sites, indicating that noradrenergic dorsal brain stem fibers (or cell bodies) support intracranial self-stimulation; (c) dorsal brain stem and hypothalamic self-stimulation sites reliably produced escape behavior; (d) simultaneous stimulation of dorsal brain stem and hypothalamic sites at subthreshold intensities interacted to produce suprathreshold response rates."}
{"id": "PMID:239050", "title": "Cross-reactive antigens and immunity to diseases caused by encapsulated bacteria.", "content": "Antigenic structures may be shared among naturally occurring polymers, including proteins and polysaccharides. Proteins are polymers of amino acids. Cross-reactions between proteins are due to similarities in their overall shape rather than their individual amino acid components. Cross-reactions have been demonstrated among proteins with similar evolutionary development and structure, such as serum albumins or immunoglobulins. Polysaccharides are polymers of monosaccharides. In contrast to proteins, antigenic specificities may be conferred by mono-, di-, and trisaccharides. Since there are about 150 known naturally occurring monosaccharides, it is not unexpected that cross-reactions are demonstrable between polysaccharides from widely divergent sources.", "contents": "Cross-reactive antigens and immunity to diseases caused by encapsulated bacteria. Antigenic structures may be shared among naturally occurring polymers, including proteins and polysaccharides. Proteins are polymers of amino acids. Cross-reactions between proteins are due to similarities in their overall shape rather than their individual amino acid components. Cross-reactions have been demonstrated among proteins with similar evolutionary development and structure, such as serum albumins or immunoglobulins. Polysaccharides are polymers of monosaccharides. In contrast to proteins, antigenic specificities may be conferred by mono-, di-, and trisaccharides. Since there are about 150 known naturally occurring monosaccharides, it is not unexpected that cross-reactions are demonstrable between polysaccharides from widely divergent sources."}
{"id": "PMID:239051", "title": "Hypersensitivity to the imported fire ant. A report of 49 cases.", "content": "Two South American species of the fire ant group, Solenopsis richteri and Solenopsis invicta, now occupy more than 150 million acres in 13 southern states and cause systemic allergic reactions to their stings. We report 49 cases of such reactions with case reports and documentation. Specificity of the sting was documented by either typical pustule formation or positive skin tests. Of 37 patients treated with hyposensitizing injections, 10 have subsequently been restung. Only one suffered a systemic reaction. Problems of cross-reactivity with other insects are discussed and the literature is reviewed. Hypersensitivity to the imported fire ant continues to be a serious problem in the southern United States and appears to be amenable to properly instituted hyposensitization therapy.", "contents": "Hypersensitivity to the imported fire ant. A report of 49 cases. Two South American species of the fire ant group, Solenopsis richteri and Solenopsis invicta, now occupy more than 150 million acres in 13 southern states and cause systemic allergic reactions to their stings. We report 49 cases of such reactions with case reports and documentation. Specificity of the sting was documented by either typical pustule formation or positive skin tests. Of 37 patients treated with hyposensitizing injections, 10 have subsequently been restung. Only one suffered a systemic reaction. Problems of cross-reactivity with other insects are discussed and the literature is reviewed. Hypersensitivity to the imported fire ant continues to be a serious problem in the southern United States and appears to be amenable to properly instituted hyposensitization therapy."}
{"id": "PMID:239052", "title": "Denaturation of deoxyribonucleic acid in situ effect of formaldehyde.", "content": "In situ denaturation of nuclear deoxyribonucleic acid (DNA) is studied by use of acridine orange to differentially stain native versus denatured DNA, and a flow-through cytofluorometer for measurements of cell fluorescence. Thermal- or acid-induced DNA denaturation is markedly influenced by formaldehyde. Two mechanisms of the formaldehyde action are distinguished. If cells are exposed to the agent during heating, DNA denaturation is facilitated, most likely by the direct action of formaldehyde as a \"passive\" denaturing agent on DNA. If cells are pretreated with formaldehyde which is then removed, DNA resistance to denaturation increases, presumably due to chromatin cross-linking. It is believed that both effects occur simultaneously in conventional techniques employing formaldehyde to study DNA in situ, and that the extent of each varies with the temperature and cell type (chromatin condensation). Thus, profiles of DNA denaturation of cells heated with formaldehyde do not represent characteristics of DNA denaturation in situ; DNA denaturation under these conditions is modulated by the reactivity of chromatin components with formaldehyde rather than by DNA interactions with the macromolecules of nuclear mileu.", "contents": "Denaturation of deoxyribonucleic acid in situ effect of formaldehyde. In situ denaturation of nuclear deoxyribonucleic acid (DNA) is studied by use of acridine orange to differentially stain native versus denatured DNA, and a flow-through cytofluorometer for measurements of cell fluorescence. Thermal- or acid-induced DNA denaturation is markedly influenced by formaldehyde. Two mechanisms of the formaldehyde action are distinguished. If cells are exposed to the agent during heating, DNA denaturation is facilitated, most likely by the direct action of formaldehyde as a \"passive\" denaturing agent on DNA. If cells are pretreated with formaldehyde which is then removed, DNA resistance to denaturation increases, presumably due to chromatin cross-linking. It is believed that both effects occur simultaneously in conventional techniques employing formaldehyde to study DNA in situ, and that the extent of each varies with the temperature and cell type (chromatin condensation). Thus, profiles of DNA denaturation of cells heated with formaldehyde do not represent characteristics of DNA denaturation in situ; DNA denaturation under these conditions is modulated by the reactivity of chromatin components with formaldehyde rather than by DNA interactions with the macromolecules of nuclear mileu."}
{"id": "PMID:239053", "title": "Demonstration of lysosomal and extralysosomal sites for acid phosphatase in mouse kidney tubule cells with p-nitrophenylphosphate lead-salt technique.", "content": "Dual localization of acid phosphatase in lysosomal and extralysosomal sites of the tubule epithelial cells of normal mouse kidney was observed at the light and electron microscope level using a modified Gomori lead-salt method with p-nitrophenylphosphate (pNPP) as substrate. Based on previous biochemical and cytochemical findings, we developed optimal conditions for the enzyme activity in extralysosomal sites. The conditions used for the light microscopic level consisted of 1.5 mM PNPP, 2.0 MM Pb(NO3)2 and 0.05 M acetate buffer (pH 5.8). Those for the electron microscopic study required 3.0 mM PNPP, 3.6 MM Pb(NO3)2 and 0.1 M acetate buffer (pH 5.8). This modified lead-salt technique was highly specific and provided a suitable method for the demonstration of nonlysosomal as well as lysosomal sites of acid phosphatase activity in the tubule epithelial cells of normal mouse kidney. As expected, the enzyme activity appeared in the lysosomes, but the prominent reaction in the brush border, the rough endoplasmic reticulum and basal infolding plasma membranes was not anticipated. We were able to demonstrate in situ organelle precursors of microsomal acid phosphatase such as endoplasmic reticulum, plasma membrane and basal infolding membranes showing the same substrate preference, which had been observed previously in biochemical studies in our laboratory. Since the possible participation of alkaline phosphatases, K+-pNPPase or Na+-K+-adenosine triphosphatase was ruled out by use of appropriate inhibitors, the enzyme-reactive sites can be interpreted as reflecting nonspecific acid phosphatase.", "contents": "Demonstration of lysosomal and extralysosomal sites for acid phosphatase in mouse kidney tubule cells with p-nitrophenylphosphate lead-salt technique. Dual localization of acid phosphatase in lysosomal and extralysosomal sites of the tubule epithelial cells of normal mouse kidney was observed at the light and electron microscope level using a modified Gomori lead-salt method with p-nitrophenylphosphate (pNPP) as substrate. Based on previous biochemical and cytochemical findings, we developed optimal conditions for the enzyme activity in extralysosomal sites. The conditions used for the light microscopic level consisted of 1.5 mM PNPP, 2.0 MM Pb(NO3)2 and 0.05 M acetate buffer (pH 5.8). Those for the electron microscopic study required 3.0 mM PNPP, 3.6 MM Pb(NO3)2 and 0.1 M acetate buffer (pH 5.8). This modified lead-salt technique was highly specific and provided a suitable method for the demonstration of nonlysosomal as well as lysosomal sites of acid phosphatase activity in the tubule epithelial cells of normal mouse kidney. As expected, the enzyme activity appeared in the lysosomes, but the prominent reaction in the brush border, the rough endoplasmic reticulum and basal infolding plasma membranes was not anticipated. We were able to demonstrate in situ organelle precursors of microsomal acid phosphatase such as endoplasmic reticulum, plasma membrane and basal infolding membranes showing the same substrate preference, which had been observed previously in biochemical studies in our laboratory. Since the possible participation of alkaline phosphatases, K+-pNPPase or Na+-K+-adenosine triphosphatase was ruled out by use of appropriate inhibitors, the enzyme-reactive sites can be interpreted as reflecting nonspecific acid phosphatase."}
{"id": "PMID:239054", "title": "An investigation into the potential hazard to animal health of effluent sludge from dairy factories.", "content": "Sixty-three samples of the more solid material (sludge) separated from the effluent plants of dairy factories were examined for the presence of salmonellas and brucellas. Salmonellas were isolated from two samples (S. heidelberg. [1]; S. indiana [1]. No brucellas were isolated. None of the samples supported the growth of S. dublin. Salmonellas added to effluent sludge at a concentration of 10(6) organisms/ml. survived less than 70 days. The sludge from dairy factory effluent plants does not appear to be a source for the spread of salmonellosis or brucellosis.", "contents": "An investigation into the potential hazard to animal health of effluent sludge from dairy factories. Sixty-three samples of the more solid material (sludge) separated from the effluent plants of dairy factories were examined for the presence of salmonellas and brucellas. Salmonellas were isolated from two samples (S. heidelberg. [1]; S. indiana [1]. No brucellas were isolated. None of the samples supported the growth of S. dublin. Salmonellas added to effluent sludge at a concentration of 10(6) organisms/ml. survived less than 70 days. The sludge from dairy factory effluent plants does not appear to be a source for the spread of salmonellosis or brucellosis."}
{"id": "PMID:239055", "title": "Relation of structure to function in bacterial endotoxins. VIII. Biological activities in a polysaccharide-rich fraction.", "content": "This is the first report describing in vivo biologic activities elicited by a non-toxic, polysaccharide-rich, water soluble fraction obtained by partial acidic hydrolysis from endotoxic lipopolysaccharide. The two activities present in this preparation were a) mouse bone marrow cell colony formation stimulation (CSF) and b) protection of mice against lethal irradiation. With polysaccharide-deficient rough mutants of salmonella minnesota, the CSF-inducing activity could be restricted to the \"core\" region of the LPS structure. Sixty-minute hydrolysis with 1 N HCl at 100 degrees C or 0.1 M sodium metaperiodate oxidation at cold room temperature completely abolished CSF-inducing activity of the preparation, whereas it showed considerable resistance to mild alkaline hydrolysis. These findings indicate that the active component in this preparation is carbohydrate in nature. Lipid preparations from smooth LPS or from Re rough mutants are either much less active or completely inactive in the above two assays. The fully active polysaccharide rich preparation was found to be inert in seven other characteristic endotoxicity parameters.", "contents": "Relation of structure to function in bacterial endotoxins. VIII. Biological activities in a polysaccharide-rich fraction. This is the first report describing in vivo biologic activities elicited by a non-toxic, polysaccharide-rich, water soluble fraction obtained by partial acidic hydrolysis from endotoxic lipopolysaccharide. The two activities present in this preparation were a) mouse bone marrow cell colony formation stimulation (CSF) and b) protection of mice against lethal irradiation. With polysaccharide-deficient rough mutants of salmonella minnesota, the CSF-inducing activity could be restricted to the \"core\" region of the LPS structure. Sixty-minute hydrolysis with 1 N HCl at 100 degrees C or 0.1 M sodium metaperiodate oxidation at cold room temperature completely abolished CSF-inducing activity of the preparation, whereas it showed considerable resistance to mild alkaline hydrolysis. These findings indicate that the active component in this preparation is carbohydrate in nature. Lipid preparations from smooth LPS or from Re rough mutants are either much less active or completely inactive in the above two assays. The fully active polysaccharide rich preparation was found to be inert in seven other characteristic endotoxicity parameters."}
{"id": "PMID:239056", "title": "Characteristics of immune interferon produced by human lymphocyte cultures compared to other human interferons.", "content": "A factor with antiviral activity has been produced in vitro by combined macrophage-lymphocyte cultures from patients with recent herpes labialis in response to HSV antigen stimulation. It has been designated \"immune interferon\" and characterized in comparison to several other human interferons. It was shown to be relatively unstable at pH 2 and at 56 degrees C. Rabbit anti-human leukocyte interferon serum was shown to be less active against immune interferon than against diploid cell interferon or against vesicle fluid interferon. The possibility of immune interferon being a totally different anti-viral protein or a protein with certain shared antigen determinants or structures with classical viral interferon is discussed. A simplified method for the assay of anti-interferon sera with microtiter plates is also described.", "contents": "Characteristics of immune interferon produced by human lymphocyte cultures compared to other human interferons. A factor with antiviral activity has been produced in vitro by combined macrophage-lymphocyte cultures from patients with recent herpes labialis in response to HSV antigen stimulation. It has been designated \"immune interferon\" and characterized in comparison to several other human interferons. It was shown to be relatively unstable at pH 2 and at 56 degrees C. Rabbit anti-human leukocyte interferon serum was shown to be less active against immune interferon than against diploid cell interferon or against vesicle fluid interferon. The possibility of immune interferon being a totally different anti-viral protein or a protein with certain shared antigen determinants or structures with classical viral interferon is discussed. A simplified method for the assay of anti-interferon sera with microtiter plates is also described."}
{"id": "PMID:239057", "title": "Effects of intravenous silica on immune and non-immune functions of the murine host.", "content": "Silica, an agent toxic for macrophages, administered i.v. to DBA/2 mice rapidly depresses the clearance of colloidal carbon by the reticuloendothelial system and reduces the in vitro phagocytic activity of peritoneal macrophages harvested 3 days after silica injection. Silica blocks the humoral immune response to sheep erythrocytes and the cell-mediated immune response to allogeneic fibroblasts when given before antigen. Silica also induces complex alterations in spleen cell responsiveness to concanavalin A involving both local and serum factors. Silica had no significant effect on the induction of interferon by statolon or Newcastle disease virus. No unequivocal evidence was obtained that silica has a direct depressive effect on cells other that macrophages, but indirect effects on lymphocytes were produced most likely by factors released from silica-lysed macrophages. Intravenous silica may prove useful for the separation of interferon induction and immune response stimulation in studies of host resistance to infection and oncogenesis. Considerable variation exists in the immunodepressive effects of different preparations of silica.", "contents": "Effects of intravenous silica on immune and non-immune functions of the murine host. Silica, an agent toxic for macrophages, administered i.v. to DBA/2 mice rapidly depresses the clearance of colloidal carbon by the reticuloendothelial system and reduces the in vitro phagocytic activity of peritoneal macrophages harvested 3 days after silica injection. Silica blocks the humoral immune response to sheep erythrocytes and the cell-mediated immune response to allogeneic fibroblasts when given before antigen. Silica also induces complex alterations in spleen cell responsiveness to concanavalin A involving both local and serum factors. Silica had no significant effect on the induction of interferon by statolon or Newcastle disease virus. No unequivocal evidence was obtained that silica has a direct depressive effect on cells other that macrophages, but indirect effects on lymphocytes were produced most likely by factors released from silica-lysed macrophages. Intravenous silica may prove useful for the separation of interferon induction and immune response stimulation in studies of host resistance to infection and oncogenesis. Considerable variation exists in the immunodepressive effects of different preparations of silica."}
{"id": "PMID:239058", "title": "The modifications of the final stages of the complement reaction by alkali metal cations.", "content": "We studied the effects of alkali metal cations on the terminal stages of complement lysis of human and sheep HK erythrocytes. Sensitized erythrocytes (EA) were reacted with limited amounts of complement for 1 hr at 37 degrees C in buffer containing 147 mM NaCl (Na buffer), which resulted in 10-40% lysis. The unlysed cells were washed with Na buffer at 0-2 degrees C and incubated for 1 hr at 37 degrees C in buffers containing 147 mM of the various alkali metal cations. Although additional lysis (25 to 65%) occurred with K, Rb, or Cs buffer, only minor degrees developed with Na or Li buffer, only minor degrees developed with Na or Li buffer. Intermediate levels occurred with 100 mM of the divalent alkali cations. Halogen ions and SCN-(147 MM), Ca++ (0.15mM), and Mg++ (0.5 mM) did not alter the effect of the alkali metal cations. Lysis occurring in K+, Rb+ or Cs+ proceeded without lag, was temperature dependent with an optimum of 43 degrees C, and had a pH optimum of 6.5. Lysis in K and Na buffers was unaffected by 10(-3) to 10(-5) M ouabain. Experiments with mixtures of cations indicated that Na+ had a mild inhibitory effect that could be totally overcome by K+, partially by Rb+, and not at all by Cs+. Li+ had a strong inhibitory effect, 6 X 10(-5) M causing 50% inhibition in buffers containing 147 mM K+, Rb+, or Cs+. By using intermediate complexes of EA and purified complement components we demonstrated that K+ enhances the lytic action of C8 on EAC1-7 as well as that of C9 on EAC1-8. It was known that Li+ facilitates lysis when acting on the entire complement reaction. We found that Li+ enhanced the lytic action of C8 on EAC1-7, with a kinetic that differed from that of the K+ effect. In addition, Li+ inhibited the enhancing effect of K+ upon lysis of EAC1-8 by C9. This occurred at concentration of Li+ similar to those which inhibited the additional lysis by K+, Rb+, and Cs+ of cells that were pretreated in Na buffer with the entire complement sequence. We propose that the major effects of alkali metal cations on complement lysis are due to their interaction with C8 and/or membrane constitutes.", "contents": "The modifications of the final stages of the complement reaction by alkali metal cations. We studied the effects of alkali metal cations on the terminal stages of complement lysis of human and sheep HK erythrocytes. Sensitized erythrocytes (EA) were reacted with limited amounts of complement for 1 hr at 37 degrees C in buffer containing 147 mM NaCl (Na buffer), which resulted in 10-40% lysis. The unlysed cells were washed with Na buffer at 0-2 degrees C and incubated for 1 hr at 37 degrees C in buffers containing 147 mM of the various alkali metal cations. Although additional lysis (25 to 65%) occurred with K, Rb, or Cs buffer, only minor degrees developed with Na or Li buffer, only minor degrees developed with Na or Li buffer. Intermediate levels occurred with 100 mM of the divalent alkali cations. Halogen ions and SCN-(147 MM), Ca++ (0.15mM), and Mg++ (0.5 mM) did not alter the effect of the alkali metal cations. Lysis occurring in K+, Rb+ or Cs+ proceeded without lag, was temperature dependent with an optimum of 43 degrees C, and had a pH optimum of 6.5. Lysis in K and Na buffers was unaffected by 10(-3) to 10(-5) M ouabain. Experiments with mixtures of cations indicated that Na+ had a mild inhibitory effect that could be totally overcome by K+, partially by Rb+, and not at all by Cs+. Li+ had a strong inhibitory effect, 6 X 10(-5) M causing 50% inhibition in buffers containing 147 mM K+, Rb+, or Cs+. By using intermediate complexes of EA and purified complement components we demonstrated that K+ enhances the lytic action of C8 on EAC1-7 as well as that of C9 on EAC1-8. It was known that Li+ facilitates lysis when acting on the entire complement reaction. We found that Li+ enhanced the lytic action of C8 on EAC1-7, with a kinetic that differed from that of the K+ effect. In addition, Li+ inhibited the enhancing effect of K+ upon lysis of EAC1-8 by C9. This occurred at concentration of Li+ similar to those which inhibited the additional lysis by K+, Rb+, and Cs+ of cells that were pretreated in Na buffer with the entire complement sequence. We propose that the major effects of alkali metal cations on complement lysis are due to their interaction with C8 and/or membrane constitutes."}
{"id": "PMID:239059", "title": "Activation of alveolar macrophages after lower respiratory tract infection.", "content": "Alveolar macrophage function has been studied in relation to bacterial infection of the lower respiratory tract. First, LRT macrophages were examined after exposure of rabbits to Listeria monocytogenes aerosols. Macrophages obtained from the LRT of animals 10 to 48 days after infection were activated, as evidenced by greater adherence to culture dishes and increased ability to ingest and kill both the original infecting organism and unrelated organisms, when compared to normal alveolar macrophages. Next, the in vitro effects on normal alveolar macrophages of incubation supernatants of control and antigen-stimulated lymphocytes (LRT and lymph node) from animals infected with L. monocytogenes or Streptococcus pneumoniae were evaluated. As manifested by increased adherence and phagocytosis, and an enhanced nonspecific bactericidal activity, alveolar macrophages were activated by the antigen-stimulated supernatants. These stimulated lymphocyte supernatants contain lymphokines (MIF), but the exact nature of the alveolar macrophage activating factor(s) remains to be determined. These observations, together with recent evidence that alveolar macrophages respond to lymphokines (MIF), suggest that the effector mechanism for cell-mediated immunity in the LRT is intact.", "contents": "Activation of alveolar macrophages after lower respiratory tract infection. Alveolar macrophage function has been studied in relation to bacterial infection of the lower respiratory tract. First, LRT macrophages were examined after exposure of rabbits to Listeria monocytogenes aerosols. Macrophages obtained from the LRT of animals 10 to 48 days after infection were activated, as evidenced by greater adherence to culture dishes and increased ability to ingest and kill both the original infecting organism and unrelated organisms, when compared to normal alveolar macrophages. Next, the in vitro effects on normal alveolar macrophages of incubation supernatants of control and antigen-stimulated lymphocytes (LRT and lymph node) from animals infected with L. monocytogenes or Streptococcus pneumoniae were evaluated. As manifested by increased adherence and phagocytosis, and an enhanced nonspecific bactericidal activity, alveolar macrophages were activated by the antigen-stimulated supernatants. These stimulated lymphocyte supernatants contain lymphokines (MIF), but the exact nature of the alveolar macrophage activating factor(s) remains to be determined. These observations, together with recent evidence that alveolar macrophages respond to lymphokines (MIF), suggest that the effector mechanism for cell-mediated immunity in the LRT is intact."}
{"id": "PMID:239060", "title": "The induction and abolition of specific immunosuppression of heart allografts in rats by use of donor blood and cyclophosphamide.", "content": "Intravenous pretreatment of WAG/Rij rats with BN blood 14 days before transplantation leads to permanent survival of BN heart allografts. Pretreatment with donor blood in the reverse donor-host combination gives rise to accelerated rejection of WAG/Rij hearts. Addition of 100 mg/kg Cy to the pretreatment with donor blood in the WAG/Rij to BN model resulted in permanent graft acceptance, presumably due to the phenomenon of immunologic enhancement. This effect could be observed only if the interval between drug administration and antigen pretreatment was short. The use of Cy had a more profound and long-lasting effect on humoral than on cellular immunity. Addition of 100 mg/kg Cy to the active enhancement protocol in the \"easy\" BN to WAG/Rij combination produced permanent graft survival in an immunologic setting reminiscent of immunologic tolerance. The combined pretreatment with donor blood and 50 mg/kg Cy in this donor-host combination abolished the operation of immunologic enhancement, which could be induced if donor blood was given alone.", "contents": "The induction and abolition of specific immunosuppression of heart allografts in rats by use of donor blood and cyclophosphamide. Intravenous pretreatment of WAG/Rij rats with BN blood 14 days before transplantation leads to permanent survival of BN heart allografts. Pretreatment with donor blood in the reverse donor-host combination gives rise to accelerated rejection of WAG/Rij hearts. Addition of 100 mg/kg Cy to the pretreatment with donor blood in the WAG/Rij to BN model resulted in permanent graft acceptance, presumably due to the phenomenon of immunologic enhancement. This effect could be observed only if the interval between drug administration and antigen pretreatment was short. The use of Cy had a more profound and long-lasting effect on humoral than on cellular immunity. Addition of 100 mg/kg Cy to the active enhancement protocol in the \"easy\" BN to WAG/Rij combination produced permanent graft survival in an immunologic setting reminiscent of immunologic tolerance. The combined pretreatment with donor blood and 50 mg/kg Cy in this donor-host combination abolished the operation of immunologic enhancement, which could be induced if donor blood was given alone."}
{"id": "PMID:239061", "title": "Specific suppression of the antibody response in vitro by serum from paralyzed mice.", "content": "BALB/c mice immunized with either the whole vaccine or the C-polysaccharide obtained from the R36A strain of pneumococcus produce antibody to phosphorylcholine. Mice injected i.v. with a single high dose of the C-polysaccharide are specifically unresponsive to immunization to phosphorylcholine for many months and are considered paralyzed. The induction of paralysis does not eliminate cells reactive to phosphorylcholine; however, serum from paralyzed mice specifically suppresses the response of cultures of normal spleen cells to phosphorylcholine. Paralyzed mice have an early low antibody response to phosphorylcholine and to the receptor for phosphorylcholine as indicated by plaque-forming cell assays. The factor or factors present in serum which may suppress cultures, and, by presumption, be responsible for paralysis are complexes of antigen, antibody, and antibody to the receptor for phosphorylcholine.", "contents": "Specific suppression of the antibody response in vitro by serum from paralyzed mice. BALB/c mice immunized with either the whole vaccine or the C-polysaccharide obtained from the R36A strain of pneumococcus produce antibody to phosphorylcholine. Mice injected i.v. with a single high dose of the C-polysaccharide are specifically unresponsive to immunization to phosphorylcholine for many months and are considered paralyzed. The induction of paralysis does not eliminate cells reactive to phosphorylcholine; however, serum from paralyzed mice specifically suppresses the response of cultures of normal spleen cells to phosphorylcholine. Paralyzed mice have an early low antibody response to phosphorylcholine and to the receptor for phosphorylcholine as indicated by plaque-forming cell assays. The factor or factors present in serum which may suppress cultures, and, by presumption, be responsible for paralysis are complexes of antigen, antibody, and antibody to the receptor for phosphorylcholine."}
{"id": "PMID:239062", "title": "Activation by some T-independent antigens and B cell mitogens of the alternative pathway of the complement system.", "content": "A number of T-independent antigens and B cell mitogens were examined for their ability to activate C3 via the alternative pathway of the complement system. Loss of hemolytically active C3, generation of anaphylatoxin activity, and immunoelectrophoretic conversion of C3 and factor B, were checked in normal and C4-deficient guinea pig serum, and, in some cases, in normal human serum. As judged by their activity in these assays, 10 lipopolysaccharides of different origin and constitution, pneumococcus type III polysaccharide, levan, dinitrophenylated aminoethyl-dextran, dinitrophenylated (D-glutamic acid, D-lysin) copolymer, polymerized flagellin, and pokeweed mitogen were all capable of initiating the alternative pathway, but differed with respect to their potency, their relative activity in the presence or absence of C4, and their ability to inhibit C3-turnover at high concentrations. Polyvinylpyrrolidone of intermediate molecular weight (4 x 10(4) daltons) was only active if the most sensitive assay was used (anaphylatoxin generation). Other species of polyvinylpyrrolidone, depolymerized pneumococcal polysaccharide, aminoethyl-dextran, [D-glutamic acid, D-lysin] copolymer, phytohemagglutinin and concanavalin A failed to activate C3. C3-consumption by concanavalin A was due to nonspecific binding.", "contents": "Activation by some T-independent antigens and B cell mitogens of the alternative pathway of the complement system. A number of T-independent antigens and B cell mitogens were examined for their ability to activate C3 via the alternative pathway of the complement system. Loss of hemolytically active C3, generation of anaphylatoxin activity, and immunoelectrophoretic conversion of C3 and factor B, were checked in normal and C4-deficient guinea pig serum, and, in some cases, in normal human serum. As judged by their activity in these assays, 10 lipopolysaccharides of different origin and constitution, pneumococcus type III polysaccharide, levan, dinitrophenylated aminoethyl-dextran, dinitrophenylated (D-glutamic acid, D-lysin) copolymer, polymerized flagellin, and pokeweed mitogen were all capable of initiating the alternative pathway, but differed with respect to their potency, their relative activity in the presence or absence of C4, and their ability to inhibit C3-turnover at high concentrations. Polyvinylpyrrolidone of intermediate molecular weight (4 x 10(4) daltons) was only active if the most sensitive assay was used (anaphylatoxin generation). Other species of polyvinylpyrrolidone, depolymerized pneumococcal polysaccharide, aminoethyl-dextran, [D-glutamic acid, D-lysin] copolymer, phytohemagglutinin and concanavalin A failed to activate C3. C3-consumption by concanavalin A was due to nonspecific binding."}
{"id": "PMID:239063", "title": "Difference in B cell mitogen responsiveness between closely related strains of mice.", "content": "Spleen cells from C3H/HeJ mice respond very poorly to the mitogenic action of endotoxin (LPS) in vitro whereas cells from a very closely related strain, C3H/HeN respond very well. An analysis of the genetic similarity of these two strains was performed. There is no significant MLR measurable between cells of these strains under a variety of culture conditions. They do not manifest a significant graft-vs-host response nor do they reject reciprocal skin grafts. Because of this genetic similarity, it is possible to reconstitute the LPS response of nonresponder mice by an adoptive transfer of spleen cells from C3H/HeN mice. This strain pair should therefore prove useful in analyzing the genetic and cellular basis of endotoxin reactivity.", "contents": "Difference in B cell mitogen responsiveness between closely related strains of mice. Spleen cells from C3H/HeJ mice respond very poorly to the mitogenic action of endotoxin (LPS) in vitro whereas cells from a very closely related strain, C3H/HeN respond very well. An analysis of the genetic similarity of these two strains was performed. There is no significant MLR measurable between cells of these strains under a variety of culture conditions. They do not manifest a significant graft-vs-host response nor do they reject reciprocal skin grafts. Because of this genetic similarity, it is possible to reconstitute the LPS response of nonresponder mice by an adoptive transfer of spleen cells from C3H/HeN mice. This strain pair should therefore prove useful in analyzing the genetic and cellular basis of endotoxin reactivity."}
{"id": "PMID:239064", "title": "Transplantation immunology of the anterior chamber of the eye. I. An intra-ocular graft-vs-host reaction (immunogenic anterior uveitis).", "content": "A graft-vs-host reaction (GVHR) expressed as an anterior uveitis was elicited within the anterior chambers of the eyes of F1 hybrid rats by the inoculation of suspensions of allogeneic, parental lymph node cells. This response resembled local GVHRs induced in other sites, except for the failure of refractoriness to appear following resolution of the acute phase. Because lymphoid cells within the anterior chamber have been shown to leave and make an impact on the systemic immunologic apparatus of the recipient, rather than remain isolated within the eye, it was suggested that the vascular route by which these cells disseminate is an important determinant of whether refractoriness will ensue from a local GVHR.", "contents": "Transplantation immunology of the anterior chamber of the eye. I. An intra-ocular graft-vs-host reaction (immunogenic anterior uveitis). A graft-vs-host reaction (GVHR) expressed as an anterior uveitis was elicited within the anterior chambers of the eyes of F1 hybrid rats by the inoculation of suspensions of allogeneic, parental lymph node cells. This response resembled local GVHRs induced in other sites, except for the failure of refractoriness to appear following resolution of the acute phase. Because lymphoid cells within the anterior chamber have been shown to leave and make an impact on the systemic immunologic apparatus of the recipient, rather than remain isolated within the eye, it was suggested that the vascular route by which these cells disseminate is an important determinant of whether refractoriness will ensue from a local GVHR."}
{"id": "PMID:239065", "title": "Transplantation immunology of the anterior chamber of the eye. II. Immune response to allogeneic cells.", "content": "The mechanism by which the anterior chamber of the eye extends immunologic privilege to allogeneic donor tissues has been studied in inbred rats. Inoculation of allogeneic lymphoid cells into the anterior chamber demonstrated that although the site lacks a lymphatic drainage, the afferent limb of the immunologic reflex arc is intact because the recipient can recognize and mount a specific immune response. In addition, host immunity was able to express itself within the anterior chamber when induced systemically, indicating that the efferent limb of the reflex arc is also intact. Therefore, it is suggested that the unique immunologic features of the anterior chamber may result from the obligate intravenous presentation of graft antigen to the host's systemic immunologic apparatus, a route that prejudices the host's response in the direction of tolerance and/or enhancement rather than cell-mediated, tissue destructive immunity.", "contents": "Transplantation immunology of the anterior chamber of the eye. II. Immune response to allogeneic cells. The mechanism by which the anterior chamber of the eye extends immunologic privilege to allogeneic donor tissues has been studied in inbred rats. Inoculation of allogeneic lymphoid cells into the anterior chamber demonstrated that although the site lacks a lymphatic drainage, the afferent limb of the immunologic reflex arc is intact because the recipient can recognize and mount a specific immune response. In addition, host immunity was able to express itself within the anterior chamber when induced systemically, indicating that the efferent limb of the reflex arc is also intact. Therefore, it is suggested that the unique immunologic features of the anterior chamber may result from the obligate intravenous presentation of graft antigen to the host's systemic immunologic apparatus, a route that prejudices the host's response in the direction of tolerance and/or enhancement rather than cell-mediated, tissue destructive immunity."}
{"id": "PMID:239067", "title": "Hapten inhibition of adsorption: specificity of the Sophora japonica lectin.", "content": "Since hapten inhibition of precipitation is relatively time consuming, we have developed a hapten inhibition of adsorption assay to explore the sugar binding specificity of the Sophora japonica lectin. Adsorbents were prepared with Sephadex and p-aminophenyl beta-D-galactopyranoside using the CNBr procedure. The ability of simple saccharides to inhibit the binding of lectin to the adsorbent was performed employing a fixed amount of adsorption with respect to the logarithm of micromoles of inhibitor yielded sigmoid shaped curves. The quantities of various saccharides required to cause 50% inhibition of the lectin--adsorbent interaction relative to D-galactose were within+/-5% of the relative inhibiting potencies of the sugars in", "contents": "Hapten inhibition of adsorption: specificity of the Sophora japonica lectin. Since hapten inhibition of precipitation is relatively time consuming, we have developed a hapten inhibition of adsorption assay to explore the sugar binding specificity of the Sophora japonica lectin. Adsorbents were prepared with Sephadex and p-aminophenyl beta-D-galactopyranoside using the CNBr procedure. The ability of simple saccharides to inhibit the binding of lectin to the adsorbent was performed employing a fixed amount of adsorption with respect to the logarithm of micromoles of inhibitor yielded sigmoid shaped curves. The quantities of various saccharides required to cause 50% inhibition of the lectin--adsorbent interaction relative to D-galactose were within+/-5% of the relative inhibiting potencies of the sugars in"}
{"id": "PMID:239069", "title": "Keratin cross-linking and epidermal transglutaminase. A review with observations on the histochemical and immunochemical localization of the enzyme.", "content": "Enzymes known as transglutaminases mediate cross-linking of polypeptide chains by epsilon-(gamma-glutamyl) lysine bonds. Such bonds stabilize structural proteins of many tissues; transglutaminases specific for these tissues have been identified. A calcium- and sulfhydryl-dependent transglutaminase with a molecular weight of 55,000 has been purified from bovine snout epidermis and used to elicit a specific antiserum to the enzyme. Sites of epidermal transglutaminase activity have been localized in the cytoplasm of upper malpighian and granular cells by two complementary methods. When thin-tissue sections were incubated with a fluorescent lysine analog(dansyl cadaverine) and calcium, tissue acceptor sites became fluorescent. Localization was confirmed by fluorescein-conjugated antibody labeling of the enzyme in situ. These observations indicate that epidermal transglutaminase cross-links epidermal proteins during the final stages of keratinization.", "contents": "Keratin cross-linking and epidermal transglutaminase. A review with observations on the histochemical and immunochemical localization of the enzyme. Enzymes known as transglutaminases mediate cross-linking of polypeptide chains by epsilon-(gamma-glutamyl) lysine bonds. Such bonds stabilize structural proteins of many tissues; transglutaminases specific for these tissues have been identified. A calcium- and sulfhydryl-dependent transglutaminase with a molecular weight of 55,000 has been purified from bovine snout epidermis and used to elicit a specific antiserum to the enzyme. Sites of epidermal transglutaminase activity have been localized in the cytoplasm of upper malpighian and granular cells by two complementary methods. When thin-tissue sections were incubated with a fluorescent lysine analog(dansyl cadaverine) and calcium, tissue acceptor sites became fluorescent. Localization was confirmed by fluorescein-conjugated antibody labeling of the enzyme in situ. These observations indicate that epidermal transglutaminase cross-links epidermal proteins during the final stages of keratinization."}
{"id": "PMID:239070", "title": "Cyclic AMP and psoriasis.", "content": "Evidence that an adenyl cyclase system is present in all mammalian epidermis is reviewed. This adenyl cyclase is stimulated by at least two separate types of chemicals: catecholamines, which act at a beta-adrenergic receptor site, and prostaglandins of the E series, which act at a separate site. In the psoriatic lesion, the response to these stimulators, especially to the catecholamines, is reduced. Despite this lack of response to external agents which elevate cyclic AMP, the concentration of cyclic AMP within the epidermis of the psoriatic lesion is no lower than in noninvolved skin. How cyclic nucleotides act to control cell proliferation and cell differentiation remains unclear.", "contents": "Cyclic AMP and psoriasis. Evidence that an adenyl cyclase system is present in all mammalian epidermis is reviewed. This adenyl cyclase is stimulated by at least two separate types of chemicals: catecholamines, which act at a beta-adrenergic receptor site, and prostaglandins of the E series, which act at a separate site. In the psoriatic lesion, the response to these stimulators, especially to the catecholamines, is reduced. Despite this lack of response to external agents which elevate cyclic AMP, the concentration of cyclic AMP within the epidermis of the psoriatic lesion is no lower than in noninvolved skin. How cyclic nucleotides act to control cell proliferation and cell differentiation remains unclear."}
{"id": "PMID:239071", "title": "Studies of the mechanism of epidermal injury by a Staphylococcal epidermolytic toxin.", "content": "Experimental animal models of the two forms of toxic epidermal necrolysis have been reviewed: a murine model of staphylococcal-induced epidermolysis and a hamster model of graft-versus-host disease. In the former, a protein exotoxin, epidermolysin, has been purified and characterized. The exotoxin has a molecular weight of approximately 30,000 and causes a split beneath the granular layer. It is effective at 3 times 10(-12) moles. Epidermolysin does not require an intact complement system for its action since B10D2 mice deficient in C5 or mice injected with the decomplementing agent in cobra venom factor were susceptible to its epidermolytic effects. Neither are immunocompetent thymocytes required for the action of the toxin since hairless, athymic adult (nu/nu) mice are susceptible. A few reports of epidermolysis due to an exotoxin of group I Staphylococcus aureus have appeared. This toxin is antigenically different from the exotoxin of group II organisms. A model of drug-induced toxic epidermal necrolysis has been described in hamsters, but the toxic principle released from sensitized lymphoid cells has not yet been characterized.", "contents": "Studies of the mechanism of epidermal injury by a Staphylococcal epidermolytic toxin. Experimental animal models of the two forms of toxic epidermal necrolysis have been reviewed: a murine model of staphylococcal-induced epidermolysis and a hamster model of graft-versus-host disease. In the former, a protein exotoxin, epidermolysin, has been purified and characterized. The exotoxin has a molecular weight of approximately 30,000 and causes a split beneath the granular layer. It is effective at 3 times 10(-12) moles. Epidermolysin does not require an intact complement system for its action since B10D2 mice deficient in C5 or mice injected with the decomplementing agent in cobra venom factor were susceptible to its epidermolytic effects. Neither are immunocompetent thymocytes required for the action of the toxin since hairless, athymic adult (nu/nu) mice are susceptible. A few reports of epidermolysis due to an exotoxin of group I Staphylococcus aureus have appeared. This toxin is antigenically different from the exotoxin of group II organisms. A model of drug-induced toxic epidermal necrolysis has been described in hamsters, but the toxic principle released from sensitized lymphoid cells has not yet been characterized."}
{"id": "PMID:239072", "title": "In vitro analysis of the control of keratinocyte proliferation in human epidermis by physiologic and pharmacologic agents.", "content": "Human keratinocytes grown in vitro as epithelial outgrowths or as organ cultures maintain many of their normal functions such as proliferation and keratinization. These in vitro systems have been used to analyze the effect of various agents on proliferation. All adenine nucleotides, including dibutyryl cyclic AMP, blocked mitosis in the G2 part of the cell cycle at concentrations of 1 times 10(-4) M. Some nonadenine nucleotides also showed this effect, but only at higher concentrations, an indication that the effect was specific for adenine nucleotides. Dibutyryl cyclic AMP and theophylline both depressed the incorporation of [3H]thymidine into DNA. Catecholamines such as isoproterenol, epinephrine, and norepinephrine were also potent inhibitors of mitosis (G2 block) at concentrations of 1 times 10(-8) to 1 times 10(-10) M. The fact that the effect could be blocked by the beta-blocking agent, propranolol, suggests the existence of specific membrane receptor sites. However, dichloroisoproterenol, another beta blocker, had distinct inhibitory properties in itself and thus indicated that the mechanism of action of catecholamines in human keratinocytes is complex and may involve more than binding to specific receptor sites. Histamine at a concentration of 2 times 10(-6) M was also a strong mitotic inhibitor. This finding is directly opposed to that in rat skin where mitosis is stimulated. Imidazole acetate, a histamine breakdown product, was found to be a striking mitotic stimulator in organ culture. A water-extractable protein (chalone) from human skin also caused a block in G2. Most of the substances tested occur naturally in the cell or organism and their ability to stimulate or depress proliferation in vitro suggests that they play a regulatory role in vivo.", "contents": "In vitro analysis of the control of keratinocyte proliferation in human epidermis by physiologic and pharmacologic agents. Human keratinocytes grown in vitro as epithelial outgrowths or as organ cultures maintain many of their normal functions such as proliferation and keratinization. These in vitro systems have been used to analyze the effect of various agents on proliferation. All adenine nucleotides, including dibutyryl cyclic AMP, blocked mitosis in the G2 part of the cell cycle at concentrations of 1 times 10(-4) M. Some nonadenine nucleotides also showed this effect, but only at higher concentrations, an indication that the effect was specific for adenine nucleotides. Dibutyryl cyclic AMP and theophylline both depressed the incorporation of [3H]thymidine into DNA. Catecholamines such as isoproterenol, epinephrine, and norepinephrine were also potent inhibitors of mitosis (G2 block) at concentrations of 1 times 10(-8) to 1 times 10(-10) M. The fact that the effect could be blocked by the beta-blocking agent, propranolol, suggests the existence of specific membrane receptor sites. However, dichloroisoproterenol, another beta blocker, had distinct inhibitory properties in itself and thus indicated that the mechanism of action of catecholamines in human keratinocytes is complex and may involve more than binding to specific receptor sites. Histamine at a concentration of 2 times 10(-6) M was also a strong mitotic inhibitor. This finding is directly opposed to that in rat skin where mitosis is stimulated. Imidazole acetate, a histamine breakdown product, was found to be a striking mitotic stimulator in organ culture. A water-extractable protein (chalone) from human skin also caused a block in G2. Most of the substances tested occur naturally in the cell or organism and their ability to stimulate or depress proliferation in vitro suggests that they play a regulatory role in vivo."}
{"id": "PMID:239073", "title": "The localization and distribution of gram-positive cocci in normal skin and in lesions of acne vulgaris.", "content": "The localization of gram-positive cocci in the normal skin and in the lesions of acne vulgaris was investigated using fluorescein-labeled antiserum raised to gram-positive, coagulase-negative cocci. The cocci were found in 10 of 19 specimens from normal facial skin and in 3 of 11 specimens from the normal skin of the rest of the body. The bacteria were found mostly in the openings of follicles, but in 6 of 10 facial skin specimens, they were also present deeply in the lumina of the dilated sebaceous follicles near the sebaceous glands. Cocci were found in 5 of 6 noninflammatory acne comedones. In inflammatory acne they were demonstrated not only in the follicular canals but also sparsely in the infiltrate surrounding the follicles.", "contents": "The localization and distribution of gram-positive cocci in normal skin and in lesions of acne vulgaris. The localization of gram-positive cocci in the normal skin and in the lesions of acne vulgaris was investigated using fluorescein-labeled antiserum raised to gram-positive, coagulase-negative cocci. The cocci were found in 10 of 19 specimens from normal facial skin and in 3 of 11 specimens from the normal skin of the rest of the body. The bacteria were found mostly in the openings of follicles, but in 6 of 10 facial skin specimens, they were also present deeply in the lumina of the dilated sebaceous follicles near the sebaceous glands. Cocci were found in 5 of 6 noninflammatory acne comedones. In inflammatory acne they were demonstrated not only in the follicular canals but also sparsely in the infiltrate surrounding the follicles."}
{"id": "PMID:239075", "title": "The effect of thiazide diuretics on carbohydrate-induced calciuria in patients with recurrent renal calculi.", "content": "Thiazide diuretics could have a beneficial effect in the prevention of recurrent renal calculi by decreasing the exaggerated calciuria which follows carbohydrate ingestionin patients who form calcium oxalate stones. The calciuric response to 100Gm. or oral glucose was studied in 21 patients with recurrent calcium stones before and after 6 months of hydrochlorothiazide therapy...", "contents": "The effect of thiazide diuretics on carbohydrate-induced calciuria in patients with recurrent renal calculi. Thiazide diuretics could have a beneficial effect in the prevention of recurrent renal calculi by decreasing the exaggerated calciuria which follows carbohydrate ingestionin patients who form calcium oxalate stones. The calciuric response to 100Gm. or oral glucose was studied in 21 patients with recurrent calcium stones before and after 6 months of hydrochlorothiazide therapy..."}
{"id": "PMID:239076", "title": "The behavior of carbenicillin as a nonreabsorbable anion.", "content": "In order to study the mechanism of hypokalemic alkalosis which occurs in some patients being treated with disodium carbenicillin, renal clearance experiments were carried out in rats and observations were made on electrical changes in isolated toad bladders. In rats maintained on a sodium-free diet, intravenous infusion of carbenicillin at 40 mg. per hour resuited in an immediate diuresis characterized by a striking increase in K and NH4 excretion, and progressive acidification of the urine. In a control group of rats, also prepared with a sodium free diet, intravenous infusion of mannitol resulted in a comparable diuresis, but no significant changes in K and NH4 excretion, and no acidification of the urine. The urinary changes in the carbenicillin-treated rats could not be accounted for by any alterations in blood electrolytes, acid-base values, or glomerular filtration rate (GFR). Isonatric, isohydric substitution of carbenicillin for chloride in the mucosal bathing media of toad bladders mounted in Ussing chambers resulted in a reversible increase in electrical potential (PD) and resistance (R) without a comparable change in short-circuit current (SCC). Substitution in the serosal medium resulted in a reversal of polarity of PD and SCC in 4 of 9 experiments, a finding best explained by more rapid movement of chloride from M leads to S than carbenicillin movement from S leads to M (a chloride diffusion potential). The observations in both the rat and toad bladder experiments are consistent with the view that carbenicillin behaves as a nonreabsorbable anion. Hypokalemic alkalosis in patients receiving this drug can thus be attributed to increased electrical negativity of the distal nephron with subsequent enhancement of K and H secretion.", "contents": "The behavior of carbenicillin as a nonreabsorbable anion. In order to study the mechanism of hypokalemic alkalosis which occurs in some patients being treated with disodium carbenicillin, renal clearance experiments were carried out in rats and observations were made on electrical changes in isolated toad bladders. In rats maintained on a sodium-free diet, intravenous infusion of carbenicillin at 40 mg. per hour resuited in an immediate diuresis characterized by a striking increase in K and NH4 excretion, and progressive acidification of the urine. In a control group of rats, also prepared with a sodium free diet, intravenous infusion of mannitol resulted in a comparable diuresis, but no significant changes in K and NH4 excretion, and no acidification of the urine. The urinary changes in the carbenicillin-treated rats could not be accounted for by any alterations in blood electrolytes, acid-base values, or glomerular filtration rate (GFR). Isonatric, isohydric substitution of carbenicillin for chloride in the mucosal bathing media of toad bladders mounted in Ussing chambers resulted in a reversible increase in electrical potential (PD) and resistance (R) without a comparable change in short-circuit current (SCC). Substitution in the serosal medium resulted in a reversal of polarity of PD and SCC in 4 of 9 experiments, a finding best explained by more rapid movement of chloride from M leads to S than carbenicillin movement from S leads to M (a chloride diffusion potential). The observations in both the rat and toad bladder experiments are consistent with the view that carbenicillin behaves as a nonreabsorbable anion. Hypokalemic alkalosis in patients receiving this drug can thus be attributed to increased electrical negativity of the distal nephron with subsequent enhancement of K and H secretion."}
{"id": "PMID:239077", "title": "Polymorphonuclear leukocyte phagocytosis: quantitation by a rapid radioactive method.", "content": "A rapid quantitative assay of phagocytosis has been developed. The method has been used to determine the phagocytic capability of human or dog polymorphonuclear leukocytes (PMN's) in a defined medium without added sera. The engulfment of 3H-labeled Staphylococcus albus is essentially complete in 30 minutes at 37 degrees C. Increase of phagocyte radioactivity is directly proportional to PMN per cubic centimeter over a wide range of cell concentrations. Maximal phagocytosis is observed at pH 7.5.", "contents": "Polymorphonuclear leukocyte phagocytosis: quantitation by a rapid radioactive method. A rapid quantitative assay of phagocytosis has been developed. The method has been used to determine the phagocytic capability of human or dog polymorphonuclear leukocytes (PMN's) in a defined medium without added sera. The engulfment of 3H-labeled Staphylococcus albus is essentially complete in 30 minutes at 37 degrees C. Increase of phagocyte radioactivity is directly proportional to PMN per cubic centimeter over a wide range of cell concentrations. Maximal phagocytosis is observed at pH 7.5."}
{"id": "PMID:239078", "title": "Bovine fibrinogen modified with 3H-acetic anhydride (3H-AcOAc).", "content": "The method is described for acetylation of bovine fibrinogen with 3H acetic anhydride (3H-AcOAc). Preparations acetylated at pH 7.8 with 10 to 40 molar excess of 3H-AcOAc were found to contain 8 to 13 moles of acetyl residues per mole of fibrinogen. The content of clottable protein and ultraviolet (UV) spectra were unchanged as compared with control unlabeled preparations. The rate of clotting with thrombin was only slightly affected. The investigations on distribution of 3H-acetyl groups in products of proteolysis of acetylated fibrinogen by thrombin demonstrated a preferential acetylation of fibrinopetide A and absence of radioactive tracer in fibrinopeptide B. Incorporation of the label into fibrinopeptide A opens the possibility for application of fibrinogen labeled with 3H-AcOAc as a convenient substrate for selective investigation on the enzymatic phase of clotting.", "contents": "Bovine fibrinogen modified with 3H-acetic anhydride (3H-AcOAc). The method is described for acetylation of bovine fibrinogen with 3H acetic anhydride (3H-AcOAc). Preparations acetylated at pH 7.8 with 10 to 40 molar excess of 3H-AcOAc were found to contain 8 to 13 moles of acetyl residues per mole of fibrinogen. The content of clottable protein and ultraviolet (UV) spectra were unchanged as compared with control unlabeled preparations. The rate of clotting with thrombin was only slightly affected. The investigations on distribution of 3H-acetyl groups in products of proteolysis of acetylated fibrinogen by thrombin demonstrated a preferential acetylation of fibrinopetide A and absence of radioactive tracer in fibrinopeptide B. Incorporation of the label into fibrinopeptide A opens the possibility for application of fibrinogen labeled with 3H-AcOAc as a convenient substrate for selective investigation on the enzymatic phase of clotting."}
{"id": "PMID:239079", "title": "Incomplete syndrome of renal tubular acidosis induced by lithium carbonate.", "content": "Renal acidification was studied in 10 control subjects and 15 lithium carbonate-treated psychiatric patients of similar age. Seven lithium-treated patients were unable to lower urine pH normally after short duration acid-loading (Li-1:5.35 to 6.25), while 8 (Li-ll:4.52 to 5.17) did not differ from control subjects (4.49 to 5.07). Li-l patients excreted significantly less titratable and net acid than the other groups. Baseline urine pH was higher in both lithium-treated groups than in control subjects, and although this was due in part to the carbonate moiety of the medication, the abnormal minimal urine pH of Li-l patients was not carbonate-dependent. Li-l patients had normal arterial pH and bicarbonate concentrations, trival bicarbonaturia, and no evidence of generalized proximal tubular dysfunction. These data demonstrate that lithium therapy can induce the syndrome of incomplete distal renal tubular acidosis at serum lithium concentrations within the accepted therapeutic range.", "contents": "Incomplete syndrome of renal tubular acidosis induced by lithium carbonate. Renal acidification was studied in 10 control subjects and 15 lithium carbonate-treated psychiatric patients of similar age. Seven lithium-treated patients were unable to lower urine pH normally after short duration acid-loading (Li-1:5.35 to 6.25), while 8 (Li-ll:4.52 to 5.17) did not differ from control subjects (4.49 to 5.07). Li-l patients excreted significantly less titratable and net acid than the other groups. Baseline urine pH was higher in both lithium-treated groups than in control subjects, and although this was due in part to the carbonate moiety of the medication, the abnormal minimal urine pH of Li-l patients was not carbonate-dependent. Li-l patients had normal arterial pH and bicarbonate concentrations, trival bicarbonaturia, and no evidence of generalized proximal tubular dysfunction. These data demonstrate that lithium therapy can induce the syndrome of incomplete distal renal tubular acidosis at serum lithium concentrations within the accepted therapeutic range."}
{"id": "PMID:239080", "title": "Enzymic reduction of cystine and glutathione in cultivated human fibroblast from normal subjects and patients with cystinosis.", "content": "Cystine glutathione transhydrogenase, cystine-reductase, and glutathion reductase activities were studied in cultivated skin fibroblasts of control subjects and of three patients with cystinosis. Specific activity, pH optima, electrophoretic mobility, and kinetic parameters were described. Evidence for two isoenzyme forms of cystine-glutathione transhydrogenase was obtained. No difference was detected in activity of biochemical characteristics of these enzymes between cells of cystinotic and normal subjects.", "contents": "Enzymic reduction of cystine and glutathione in cultivated human fibroblast from normal subjects and patients with cystinosis. Cystine glutathione transhydrogenase, cystine-reductase, and glutathion reductase activities were studied in cultivated skin fibroblasts of control subjects and of three patients with cystinosis. Specific activity, pH optima, electrophoretic mobility, and kinetic parameters were described. Evidence for two isoenzyme forms of cystine-glutathione transhydrogenase was obtained. No difference was detected in activity of biochemical characteristics of these enzymes between cells of cystinotic and normal subjects."}
{"id": "PMID:239084", "title": "Sodium regulation in the larvae of Chironomus dorsalis (Meig.) and Camptochironomus tentans (Fabr.): the effect of slat depletion and some observations on temperature changes.", "content": "Sodium regulation was studied in fourth instar larvae of Chironomus dorsalis and Camptochironomus tentans. Both maintain a body sodium level well above that of the surrounding medium. The haemolymph contains approximately 90% of total body sodium and approximates to a single compartment freely exchanging sodium with the external medium. The anal papillae play a primary role in sodium regulation, the gut being in secondary importance. Sodium regulation in both species is comparatively insensitive to alterations in acclimatization temperature. C. dorsalis and C. tentans are capable of maintaining sodium balance in media containing 10 mumole Na and 25 mumole Na respectively. When exposed to several changes of distilled water, C. tentansis capable of reducing sodium loss by elaboration of a more dilute urine. This is apparently,supplemented by a reduction in the permeability of the body surface. Activation of sodium uptake in both species is comparatively sluggish, with influx reaching a maximum only after the loss of greater than 30% body sodium.", "contents": "Sodium regulation in the larvae of Chironomus dorsalis (Meig.) and Camptochironomus tentans (Fabr.): the effect of slat depletion and some observations on temperature changes. Sodium regulation was studied in fourth instar larvae of Chironomus dorsalis and Camptochironomus tentans. Both maintain a body sodium level well above that of the surrounding medium. The haemolymph contains approximately 90% of total body sodium and approximates to a single compartment freely exchanging sodium with the external medium. The anal papillae play a primary role in sodium regulation, the gut being in secondary importance. Sodium regulation in both species is comparatively insensitive to alterations in acclimatization temperature. C. dorsalis and C. tentans are capable of maintaining sodium balance in media containing 10 mumole Na and 25 mumole Na respectively. When exposed to several changes of distilled water, C. tentansis capable of reducing sodium loss by elaboration of a more dilute urine. This is apparently,supplemented by a reduction in the permeability of the body surface. Activation of sodium uptake in both species is comparatively sluggish, with influx reaching a maximum only after the loss of greater than 30% body sodium."}
{"id": "PMID:239085", "title": "The effect of enternal sodium concentration upon sodium fluxes in Chironomus dorsalis (Meig.) and Camptochironomus tentans (Fabr.), and the effect of other ions on sodium influx in C. tentans.", "content": "In comparison with other freshwater animals, the sodium uptake mechanism in fourth instar larvae of both C. tentans and C. dorsalis has a moderate affinity for sodium. In both species half maximum influx (Km) occurs at about 0.57 mM-Na+ and is unaltered by salt depletion. Maximum influx is achieved in steady-state C. tentans at 1.9 mM-Na+, and in steady-state C. dorsalis at 3.0 mM-Na+. Both of these values increase on depletion. Efflux also appears to be saturable at higher external sodium concentrations. In C. tentans, sodium may be transported independently of chloride, although it seems likely that sodium movement is enhanced by chloride. Sulphate strongly inhibits sodium influx. Nitrate apparently inhibits sodium influx at low concentrations, but this inhibition is progressively overcome at external sodium concentrations approaching 4 mM. A number of cations interfere with sodium influx in depleted C. tentans, notably H+, Li+ and, to a lesser extent NH4+. It is suggested that these ions compete with sodium for carrier sites. Potassium is apparently transported independently of sodium.", "contents": "The effect of enternal sodium concentration upon sodium fluxes in Chironomus dorsalis (Meig.) and Camptochironomus tentans (Fabr.), and the effect of other ions on sodium influx in C. tentans. In comparison with other freshwater animals, the sodium uptake mechanism in fourth instar larvae of both C. tentans and C. dorsalis has a moderate affinity for sodium. In both species half maximum influx (Km) occurs at about 0.57 mM-Na+ and is unaltered by salt depletion. Maximum influx is achieved in steady-state C. tentans at 1.9 mM-Na+, and in steady-state C. dorsalis at 3.0 mM-Na+. Both of these values increase on depletion. Efflux also appears to be saturable at higher external sodium concentrations. In C. tentans, sodium may be transported independently of chloride, although it seems likely that sodium movement is enhanced by chloride. Sulphate strongly inhibits sodium influx. Nitrate apparently inhibits sodium influx at low concentrations, but this inhibition is progressively overcome at external sodium concentrations approaching 4 mM. A number of cations interfere with sodium influx in depleted C. tentans, notably H+, Li+ and, to a lesser extent NH4+. It is suggested that these ions compete with sodium for carrier sites. Potassium is apparently transported independently of sodium."}
{"id": "PMID:239086", "title": "The relationship between transepithelial sodium movement and potential difference in the larva of Camptochironomus tentans (Fabr.) and some observations on the accumulation of other ions.", "content": "In fourth instar larvae of Camptochironomus tentans, net sodium uptake from 2 mM-NaCl has an electrogenic component. During net uptake the transepithelial potential (TEP) alters from a value of approximately - 40 mV (sign refers to haemolymph), in depleted animals, to approximately o mV. The TEP in depleted larvae is dependent upon external sodium concentration above about I mM-Na+, becoming increasingly electropositive (haemolymph relative to medium) at high sodium concentrations. This effect is exaggerated in Na2SO4 compared with NaCl. At an external concentration of 2mM-NaCl, chloride is carried by an electroneutral mechanism, probably a closely coupled Cl-/anion exchange. However, it is possible that chloride transport could become somewhat electrogenic at higher concentrations. Lithium competes with sodium for the electrogenic pump. Observed TEPs differ greatly from those required to maintain passively the haemolymph concentrations of sodium and chloride.", "contents": "The relationship between transepithelial sodium movement and potential difference in the larva of Camptochironomus tentans (Fabr.) and some observations on the accumulation of other ions. In fourth instar larvae of Camptochironomus tentans, net sodium uptake from 2 mM-NaCl has an electrogenic component. During net uptake the transepithelial potential (TEP) alters from a value of approximately - 40 mV (sign refers to haemolymph), in depleted animals, to approximately o mV. The TEP in depleted larvae is dependent upon external sodium concentration above about I mM-Na+, becoming increasingly electropositive (haemolymph relative to medium) at high sodium concentrations. This effect is exaggerated in Na2SO4 compared with NaCl. At an external concentration of 2mM-NaCl, chloride is carried by an electroneutral mechanism, probably a closely coupled Cl-/anion exchange. However, it is possible that chloride transport could become somewhat electrogenic at higher concentrations. Lithium competes with sodium for the electrogenic pump. Observed TEPs differ greatly from those required to maintain passively the haemolymph concentrations of sodium and chloride."}
{"id": "PMID:239087", "title": "The uptake of L-glutamate by the central nervous system of the cockroach, Periplaneta americana.", "content": "A concentrative uptake mechanism for L-glutamate with the following characteristics has been identified in the abdominal nerve cord: 1. The uptake can be divided into Na+-sensitive and Na-plus-insensitive components. 2. The Na-plus-sensitive component showed the typical saturation kinetics of a carrier mediate process. It had a V of 15.9 x 10(6) times 10(6) muM/mg wet weight/min and a Km of 0-33 mm. Its magnitude was proportional to the first power of the Na-plus concentration of the medium. The uptake was specific for L-dicarboxylic amino acids and was sensitive to the presence of metabolic inhibitors. 3. The Na-plus-insensitive component was linearly related to the glutamate concentration of the medium. An isosmotic saline is described for use with the isolated intact abdominal nerve cord of P. americana.", "contents": "The uptake of L-glutamate by the central nervous system of the cockroach, Periplaneta americana. A concentrative uptake mechanism for L-glutamate with the following characteristics has been identified in the abdominal nerve cord: 1. The uptake can be divided into Na+-sensitive and Na-plus-insensitive components. 2. The Na-plus-sensitive component showed the typical saturation kinetics of a carrier mediate process. It had a V of 15.9 x 10(6) times 10(6) muM/mg wet weight/min and a Km of 0-33 mm. Its magnitude was proportional to the first power of the Na-plus concentration of the medium. The uptake was specific for L-dicarboxylic amino acids and was sensitive to the presence of metabolic inhibitors. 3. The Na-plus-insensitive component was linearly related to the glutamate concentration of the medium. An isosmotic saline is described for use with the isolated intact abdominal nerve cord of P. americana."}
{"id": "PMID:239088", "title": "Tracing of cells of the avian thymus through embryonic life in interspecific chimeras.", "content": "Differences in the structure of the interphase nucleus between two species of birds, the Japanese quail (Coturnix coturnix japonica) and the chick (Gallus gallus) has been used to distinguish cells from different origins in interspecies combinations. This biological cell marking technique was applied to thymus histogenesis. Using various combinations between components of quail and chick thymic rudiments, the respective contribution of endodermal epithelium, mesenchyme, and blood-borne extrinsic elements to the histogenesis of thymus was analyzed. It was demonstrated that the whole lymphoid population of the thymus is derived from immigrant blood-borne stem cells which are chemically attracted by the endoderm of the 3rd and 4th pharyngeal pouch. The latter is determined to differentiate into thymic epithelial reticulum as soon as the 15-somite stage, and is able to attract blood stem cells even when transplanted in an heterotopic position such as the ventral body wall of the embryo. It was shown that the thymic mesenchyme originates from the neural crest mesectoderm which colonizes early the 3rd and 4th branchial arches. It participates in the formation of perivascular mesenchyme, but does not give rise to lymphocytes. From heterospecific transplantations of quail thymuses into chick embryo (and inversely) at various stages of development is appeared that the thymic rudiment becomes attractive for lymphoid stem cells at a precise stage of its evolution for each species. The attractivity period lasts about 24 h for the quail and 36 h for the chick. Then, the inflow of stem cells becomes very low until the end of the incubation period. At this time, a second wave of lymphocytoblasts invades the thymus and the primitive embryonic lymphoid population is completely renewed around the hatching time. Competent thymic stem cells are present in the blood before and after the period of physiological thymic attractivity. The identity of basophilic cells appearing in the thymus during its histogenesis and lymphoid stem cells has been demonstrated from the analysis of quail-chick chimeric thymuses.", "contents": "Tracing of cells of the avian thymus through embryonic life in interspecific chimeras. Differences in the structure of the interphase nucleus between two species of birds, the Japanese quail (Coturnix coturnix japonica) and the chick (Gallus gallus) has been used to distinguish cells from different origins in interspecies combinations. This biological cell marking technique was applied to thymus histogenesis. Using various combinations between components of quail and chick thymic rudiments, the respective contribution of endodermal epithelium, mesenchyme, and blood-borne extrinsic elements to the histogenesis of thymus was analyzed. It was demonstrated that the whole lymphoid population of the thymus is derived from immigrant blood-borne stem cells which are chemically attracted by the endoderm of the 3rd and 4th pharyngeal pouch. The latter is determined to differentiate into thymic epithelial reticulum as soon as the 15-somite stage, and is able to attract blood stem cells even when transplanted in an heterotopic position such as the ventral body wall of the embryo. It was shown that the thymic mesenchyme originates from the neural crest mesectoderm which colonizes early the 3rd and 4th branchial arches. It participates in the formation of perivascular mesenchyme, but does not give rise to lymphocytes. From heterospecific transplantations of quail thymuses into chick embryo (and inversely) at various stages of development is appeared that the thymic rudiment becomes attractive for lymphoid stem cells at a precise stage of its evolution for each species. The attractivity period lasts about 24 h for the quail and 36 h for the chick. Then, the inflow of stem cells becomes very low until the end of the incubation period. At this time, a second wave of lymphocytoblasts invades the thymus and the primitive embryonic lymphoid population is completely renewed around the hatching time. Competent thymic stem cells are present in the blood before and after the period of physiological thymic attractivity. The identity of basophilic cells appearing in the thymus during its histogenesis and lymphoid stem cells has been demonstrated from the analysis of quail-chick chimeric thymuses."}
{"id": "PMID:239089", "title": "Serum-mediated inhibition of graft-vs.-host reaction.", "content": "Rats recovering from a systemic graft-vs.-host reaction (GVHR) possess factors in the serum which can inhibit the production of a local GVHR. After incubation in vitro for 1 h at 37 degrees C these factors reduce the GVH-producing potential of parental spleen or lymph node cells to 24% of control cells treated with normal serum. These factors appear within 1 wk after initiation of a systemic GVHR and some residual activity persists for up to 8 mo. The serum activity was present in the globulin fraction and was completely removed by absorption with spleen, lymph node, or kidney homogenates from either parental strain rats. These studies indicate that during the course of a systemic GVHR, serum factors directed against the host appear in the circulation and tend to inhibit the production of further GVHR by a second challenge of either parental strain cells.", "contents": "Serum-mediated inhibition of graft-vs.-host reaction. Rats recovering from a systemic graft-vs.-host reaction (GVHR) possess factors in the serum which can inhibit the production of a local GVHR. After incubation in vitro for 1 h at 37 degrees C these factors reduce the GVH-producing potential of parental spleen or lymph node cells to 24% of control cells treated with normal serum. These factors appear within 1 wk after initiation of a systemic GVHR and some residual activity persists for up to 8 mo. The serum activity was present in the globulin fraction and was completely removed by absorption with spleen, lymph node, or kidney homogenates from either parental strain rats. These studies indicate that during the course of a systemic GVHR, serum factors directed against the host appear in the circulation and tend to inhibit the production of further GVHR by a second challenge of either parental strain cells."}
{"id": "PMID:239090", "title": "A rapid technique for preparation of human fetal and adult skeletal material.", "content": "The techniques described above have been found to provide a rapid method of human skeletal preparation, with advantages of speed and applicability to fresh, fixed, or partially decomposed skeletal materials.  While other techniques which can be used include the traditional use of Dermestidae beetle colonies, a five-step anatomical procedure, and other combinations of chemical solvents, the antiformin technique appears to have advantages useful to those involved in forensic medicine.", "contents": "A rapid technique for preparation of human fetal and adult skeletal material. The techniques described above have been found to provide a rapid method of human skeletal preparation, with advantages of speed and applicability to fresh, fixed, or partially decomposed skeletal materials.  While other techniques which can be used include the traditional use of Dermestidae beetle colonies, a five-step anatomical procedure, and other combinations of chemical solvents, the antiformin technique appears to have advantages useful to those involved in forensic medicine."}
{"id": "PMID:239091", "title": "Studies of lactate dehydrogenase of Mycoplasma mycoides var. mycoides.", "content": "Polyacrylamide gel electrophoresis and isoelectric focusing techniques have been used to compare NAD-dependent L(plus) lactate dehydrogenases (LDH) from ten different strains of Mycoplasma mycoides var. mycoides. The enzymes were not distinguished from one another, or from normal bovine LDH 1 by these methods. The kinetic behaviour of LDH form M. mycoides (T1 vaccine strain) suggested that the enzyme could readily reduce pyruvate or oxidize lactate in a manner which, in vertebrates, requires two different isoenzymes.", "contents": "Studies of lactate dehydrogenase of Mycoplasma mycoides var. mycoides. Polyacrylamide gel electrophoresis and isoelectric focusing techniques have been used to compare NAD-dependent L(plus) lactate dehydrogenases (LDH) from ten different strains of Mycoplasma mycoides var. mycoides. The enzymes were not distinguished from one another, or from normal bovine LDH 1 by these methods. The kinetic behaviour of LDH form M. mycoides (T1 vaccine strain) suggested that the enzyme could readily reduce pyruvate or oxidize lactate in a manner which, in vertebrates, requires two different isoenzymes."}
{"id": "PMID:239092", "title": "An analysis of intermediary metabolism and its control in a fat-synthesizing yeast (Candida 107) growing on glucose or alkanes.", "content": "Enzymes of glycolysis, pentose phosphate pathway, gluconeogenesis, tricarboxylate acid cycle, glyoxylate by-pass and fatty-acid biosynthesis were assayed in extracts from Candida 107 grown continuously on glucose under carbon limitation, nitrogen limitation and on n-alkanes. The yeast was therefore either in a lipogenic or lipolytic state. Phosphofructokinase was absent under all conditions whereas enzymes of gluconeogenesis, including fructose 1,6-bisphosphatase and the pentose phosphate cycle, were all present. Glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were specific for NADP+ and were inhibited in a non-competitive manner by NADPH and NADH. Phosphoenolpyruvate, citrate, ATP and acetyl CoA had no inhibitory effects. Thus glucose metabolism appears to be by the pentose phosphate pathway which will rapidly produce NADPH. This can readily be consumed during fatty-acid biosynthesis and, as there appears to be no inhibition of the flow of carbon from glucose to acetyl CoA, fatty-acid synthesis can continue for as long as there is a supply of glucose. These results help to explain the probable causes of fat build-up to high concentrations (about 40% of the cell dry weight) in this and other organisms. In alkane-grown cells, lipogenesis is repressed and carbon is able to flow from the alkanes via acetyl CoA, oxaloacetate and pyruvate into pentoses and hexoses in a unidirectional manner, because of the strong repression of pyruvate kinase and the increased activities of phosphoenolpyruvate kinase and fructose 1,6-biosphosphatase under these conditions. Although there was little change in the total activity of the TCA cycle enzymes under the various growth conditions, isocitrate lyase was induced under lipolytic conditions.", "contents": "An analysis of intermediary metabolism and its control in a fat-synthesizing yeast (Candida 107) growing on glucose or alkanes. Enzymes of glycolysis, pentose phosphate pathway, gluconeogenesis, tricarboxylate acid cycle, glyoxylate by-pass and fatty-acid biosynthesis were assayed in extracts from Candida 107 grown continuously on glucose under carbon limitation, nitrogen limitation and on n-alkanes. The yeast was therefore either in a lipogenic or lipolytic state. Phosphofructokinase was absent under all conditions whereas enzymes of gluconeogenesis, including fructose 1,6-bisphosphatase and the pentose phosphate cycle, were all present. Glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were specific for NADP+ and were inhibited in a non-competitive manner by NADPH and NADH. Phosphoenolpyruvate, citrate, ATP and acetyl CoA had no inhibitory effects. Thus glucose metabolism appears to be by the pentose phosphate pathway which will rapidly produce NADPH. This can readily be consumed during fatty-acid biosynthesis and, as there appears to be no inhibition of the flow of carbon from glucose to acetyl CoA, fatty-acid synthesis can continue for as long as there is a supply of glucose. These results help to explain the probable causes of fat build-up to high concentrations (about 40% of the cell dry weight) in this and other organisms. In alkane-grown cells, lipogenesis is repressed and carbon is able to flow from the alkanes via acetyl CoA, oxaloacetate and pyruvate into pentoses and hexoses in a unidirectional manner, because of the strong repression of pyruvate kinase and the increased activities of phosphoenolpyruvate kinase and fructose 1,6-biosphosphatase under these conditions. Although there was little change in the total activity of the TCA cycle enzymes under the various growth conditions, isocitrate lyase was induced under lipolytic conditions."}
{"id": "PMID:239093", "title": "Malonate as a precursor in the biosynthesis of aflatoxins.", "content": "Incorporation of [I-14C]acetate and [2-14C]malonate into aflatoxins by resting mycelia of Aspergillus parasiticus resuspended in different buffers was studied. A decrease in pH from 5-8 to 2-8, as well as addition of EDTA, markedly stimulated the incorporation of malonate but the effect on acetate incorporation was less pronounced. Mycelia took up comparatively more acetate than malonate, but more malonate (4-3%) entering mycelia was incorporated into aflatoxins than was acetate (1-6%). Furthermore, the addition of unlabelled acetate reduced the incorporation of label from [I-14C]acetate by 75% but from [2-14C]malonate by only 25%. These results suggest that malonate is an intermediate in aflatoxin synthesis and that is can be incorporated without prior conversion to acetate.", "contents": "Malonate as a precursor in the biosynthesis of aflatoxins. Incorporation of [I-14C]acetate and [2-14C]malonate into aflatoxins by resting mycelia of Aspergillus parasiticus resuspended in different buffers was studied. A decrease in pH from 5-8 to 2-8, as well as addition of EDTA, markedly stimulated the incorporation of malonate but the effect on acetate incorporation was less pronounced. Mycelia took up comparatively more acetate than malonate, but more malonate (4-3%) entering mycelia was incorporated into aflatoxins than was acetate (1-6%). Furthermore, the addition of unlabelled acetate reduced the incorporation of label from [I-14C]acetate by 75% but from [2-14C]malonate by only 25%. These results suggest that malonate is an intermediate in aflatoxin synthesis and that is can be incorporated without prior conversion to acetate."}
{"id": "PMID:239094", "title": "Effect of pH and haem compounds on the killing of Pasteurella septica by specific antiserum.", "content": "The killing of Pasteurella septica by horse antiserum has features not previously associated with serum bactericidal reactions. The present work showed that lowering the pH from 7-4 to 6-8 abolished the action of antiserum. The bactericidal effect and the degradation of RNA seen when antiserum is added to P. septica growing in horse serum, were abolished at pH 6-8 in much the same way as when haem compounds were added to the system. Addition of chloramphenicol, rifampicin or puromycin to P. septica growing apparently normally in antiserum at pH 6-8 or in antiserum containing haem compounds led to rapid killing of the bacteria and to degration of their RNA. Addition of these antibiotics to P. septica growing in normal serum produced only bacteriostasis and did not induce RNA breakdown. In contrast, nalidixic acid, although inhibiting growth, did not induce rapid killing and RNA breakdown under the same conditions. These findings were unexpected and led to a reassessment of ideas concerning the mechanism of action of specific antiserum to P. septica. Although iron compounds clearly abolish the bactericidal based simply on an interference with bacterial iron supply is no longer sufficient. The process is more complex and must involve other factors.", "contents": "Effect of pH and haem compounds on the killing of Pasteurella septica by specific antiserum. The killing of Pasteurella septica by horse antiserum has features not previously associated with serum bactericidal reactions. The present work showed that lowering the pH from 7-4 to 6-8 abolished the action of antiserum. The bactericidal effect and the degradation of RNA seen when antiserum is added to P. septica growing in horse serum, were abolished at pH 6-8 in much the same way as when haem compounds were added to the system. Addition of chloramphenicol, rifampicin or puromycin to P. septica growing apparently normally in antiserum at pH 6-8 or in antiserum containing haem compounds led to rapid killing of the bacteria and to degration of their RNA. Addition of these antibiotics to P. septica growing in normal serum produced only bacteriostasis and did not induce RNA breakdown. In contrast, nalidixic acid, although inhibiting growth, did not induce rapid killing and RNA breakdown under the same conditions. These findings were unexpected and led to a reassessment of ideas concerning the mechanism of action of specific antiserum to P. septica. Although iron compounds clearly abolish the bactericidal based simply on an interference with bacterial iron supply is no longer sufficient. The process is more complex and must involve other factors."}
{"id": "PMID:239095", "title": "An altered invertase in the cot-2 mutant of Neurospora crassa.", "content": "Because the cot-2 and inv loci of Neurospora crassa are closely linked, the invertase from the morphological mutant, cot-2, was examined. The cot-2 strains produce an invertase with altered heat sensitivity, Km, and ratio of heavy to light forms. The cellular localization of cot-2 invertase is different from that of the wild type. There were no observable changes in the energy of activation or the pH optimum of cot-2 invertase, and some of the differences detected were not apparent under culture conditions that promoted wild-type growth. Since recombination (about 5 percent) occurred between cot-2 and inv and culture conditions affected the enzyme characteristics, we suggest cot-2 determines, in part, the carbohydrate composition of the enzyme.", "contents": "An altered invertase in the cot-2 mutant of Neurospora crassa. Because the cot-2 and inv loci of Neurospora crassa are closely linked, the invertase from the morphological mutant, cot-2, was examined. The cot-2 strains produce an invertase with altered heat sensitivity, Km, and ratio of heavy to light forms. The cellular localization of cot-2 invertase is different from that of the wild type. There were no observable changes in the energy of activation or the pH optimum of cot-2 invertase, and some of the differences detected were not apparent under culture conditions that promoted wild-type growth. Since recombination (about 5 percent) occurred between cot-2 and inv and culture conditions affected the enzyme characteristics, we suggest cot-2 determines, in part, the carbohydrate composition of the enzyme."}
{"id": "PMID:239096", "title": "Studies on the purification of chlamydial agents grown in yolk sacs of embryonated eggs using disulphide-linked immunosorbents and enzymes.", "content": "Immunosorbents were derived from avid and non-avid sera raised in rabbits to multiple or single injections of chlamydiae passaged once or three times in HeLa cells after routine passage in eggs. Egg-derived suspensions of chlamydiae required pretreatment before application to immunosorbent columns; this was most conveniently done by fractionation on Sepharose 4B. Immunosorbents derived from avid serum had greater capacity than those from non-avid sera. However, organisms were desorbed in low yield from an avid immunosorbent, but in higher yields from non-avid immunosorbents. Even under the best conditions, the immunosorbents yielded suspensions of organisms still contaminated with egg antigens. Partially purified suspensions of chlamydiae were also treated with phospholipase C to yield suspensions of high purity.", "contents": "Studies on the purification of chlamydial agents grown in yolk sacs of embryonated eggs using disulphide-linked immunosorbents and enzymes. Immunosorbents were derived from avid and non-avid sera raised in rabbits to multiple or single injections of chlamydiae passaged once or three times in HeLa cells after routine passage in eggs. Egg-derived suspensions of chlamydiae required pretreatment before application to immunosorbent columns; this was most conveniently done by fractionation on Sepharose 4B. Immunosorbents derived from avid serum had greater capacity than those from non-avid sera. However, organisms were desorbed in low yield from an avid immunosorbent, but in higher yields from non-avid immunosorbents. Even under the best conditions, the immunosorbents yielded suspensions of organisms still contaminated with egg antigens. Partially purified suspensions of chlamydiae were also treated with phospholipase C to yield suspensions of high purity."}
{"id": "PMID:239100", "title": "Effect of ornithine alpha oxoglutarate on brain metabolism in patients with chronic liver disease.", "content": "Patients with chronic liver disease, yet without severe encephalopathy, were found to show evidence of increased brain utilization of glucose. The changes were abolished after an intravenous infusion of 15 g ornithine alpha oxoglutarate, given over a period of 15 minutes. The possible implications of these observations are discussed.", "contents": "Effect of ornithine alpha oxoglutarate on brain metabolism in patients with chronic liver disease. Patients with chronic liver disease, yet without severe encephalopathy, were found to show evidence of increased brain utilization of glucose. The changes were abolished after an intravenous infusion of 15 g ornithine alpha oxoglutarate, given over a period of 15 minutes. The possible implications of these observations are discussed."}
{"id": "PMID:239101", "title": "Involuntary movements caused by phenytoin intoxication in epileptic patients.", "content": "The case histories of four patients who developed choreoathetoid movements during intoxication with phenytoin are presented. Drug intoxication was confirmed in each case by measuring the serum phenytoin concentration. Drug interactions were, in part, responsible for the occurrence of intoxication in three of them. Phenytoin intoxication is not always easy to recognize, particularly when nystagmus is minimal or absent, as in these four patients. The estimation of the serum phenytoin concentration is invaluable in this situation.", "contents": "Involuntary movements caused by phenytoin intoxication in epileptic patients. The case histories of four patients who developed choreoathetoid movements during intoxication with phenytoin are presented. Drug intoxication was confirmed in each case by measuring the serum phenytoin concentration. Drug interactions were, in part, responsible for the occurrence of intoxication in three of them. Phenytoin intoxication is not always easy to recognize, particularly when nystagmus is minimal or absent, as in these four patients. The estimation of the serum phenytoin concentration is invaluable in this situation."}
{"id": "PMID:239102", "title": "Haemorrhagic and perivenous encephalitis: a clinical-pathological review of 38 cases.", "content": "Clinical and pathological data from eight cases of acute haemorrhagic leucoencephalitis (AHL) confirm the previously documented devastating features of this disease. Data from 30 cases of perivenous encephalitis (PVE) associated with viral diseases reveal pathological changes ranging from lymphocytic cuffing of vessels to severe vasculitis similar to the vasculitis of AHL. Relatively few cases show demyelination as a prominent feature. The pathological changes are unrelated to the type of underlying disease with the exception that the pathology of 'post-rubella' encephalitis tends to be mild. Two cases of rubeola and two of mumps showed viral nodules in the cortex, raising the possibility of direct viral invasion of tissue. Allowing for species differences, these changes are analogous to the pathological features of experimental allergic encephalitis (EAE); with the various pathological changes of PVE paralleling the features of ordinary EAE, while the changes of AHL and the severe cases of PVE strongly resemble hyperacute EAE.", "contents": "Haemorrhagic and perivenous encephalitis: a clinical-pathological review of 38 cases. Clinical and pathological data from eight cases of acute haemorrhagic leucoencephalitis (AHL) confirm the previously documented devastating features of this disease. Data from 30 cases of perivenous encephalitis (PVE) associated with viral diseases reveal pathological changes ranging from lymphocytic cuffing of vessels to severe vasculitis similar to the vasculitis of AHL. Relatively few cases show demyelination as a prominent feature. The pathological changes are unrelated to the type of underlying disease with the exception that the pathology of 'post-rubella' encephalitis tends to be mild. Two cases of rubeola and two of mumps showed viral nodules in the cortex, raising the possibility of direct viral invasion of tissue. Allowing for species differences, these changes are analogous to the pathological features of experimental allergic encephalitis (EAE); with the various pathological changes of PVE paralleling the features of ordinary EAE, while the changes of AHL and the severe cases of PVE strongly resemble hyperacute EAE."}
{"id": "PMID:239103", "title": "Intestinal absorption of cytidine diphosphate choline and its changes in the digestive tract.", "content": "Intestinal absorption of cytidine diphosphate choline (CDP-choline), its structural changes in the digestive tract, and hepatic uptake have been investigated in rats using 14C-labeled (14CH3 attached to N of choline) and 3H-labeled (at C5 of pyrimidine) compounds. The results indicate that: 1)CDP-choline is relatively stable in the stomach, but is quickly degraded into cytidine and choline in the intestine; 2) The hepatic uptakes of 14C and 3H reach the maximum in two to three hours after oral administration; 3) Whereas the amount of 14C remaining in the gut is inversely related to the hepatic uptake, no similar correlation is seen with 3H-labeled CDP-choline, and 4) Extrahepatic uptake of 14C and 3H is very small. The possibility of phosphorylation in the mucosa of choline and cytidine has been discussed, based on the differences in individual broken-down products in the intestinal lumen and mucosa.", "contents": "Intestinal absorption of cytidine diphosphate choline and its changes in the digestive tract. Intestinal absorption of cytidine diphosphate choline (CDP-choline), its structural changes in the digestive tract, and hepatic uptake have been investigated in rats using 14C-labeled (14CH3 attached to N of choline) and 3H-labeled (at C5 of pyrimidine) compounds. The results indicate that: 1)CDP-choline is relatively stable in the stomach, but is quickly degraded into cytidine and choline in the intestine; 2) The hepatic uptakes of 14C and 3H reach the maximum in two to three hours after oral administration; 3) Whereas the amount of 14C remaining in the gut is inversely related to the hepatic uptake, no similar correlation is seen with 3H-labeled CDP-choline, and 4) Extrahepatic uptake of 14C and 3H is very small. The possibility of phosphorylation in the mucosa of choline and cytidine has been discussed, based on the differences in individual broken-down products in the intestinal lumen and mucosa."}
{"id": "PMID:239104", "title": "Purification and properties of the dihydrofolate synthetase from pea seedlings.", "content": "Dihydrofolate synthetase [EC 6.3.2.12] was extracted from the cell particles (mitochondrial fraction) of pea seedlings and purified about 2,000-fold by ammonium sulfate fraction, DEAE-cellulose column chromatography, Sephades G-200 gel filtration, and hydroxylapatite column chromatography. The enzyme preparation obtained was confirmed ultracentrifugally to be in the homogeneous state. The sedimentation coefficient of this enzyme was calculated as 3.9S. The apparent molecular weight of the enzyme was determined to be about 56,000. Optimum pH for the reaction was 8.8. The enzymatic reaction required dihydropteroate, L-glutamate and ATP as substrates, and divalent (Mg2+ or Mn 2+) and univalent K+, NH4+ OR Rb+) cations as cofactors. The enzyme was specific for dihydropteroic acid as the substrate. ATP was not replaceable with any other nucleotides. Km values for dihydropteroate, L-glutamate, ATP, Mg2+, and Mn2+ were 1.0 X 10 MINUS 6, 1.5 X 10 MINUS 3, 1.0 X 10 MINUS 4, 1.1 X 10 MINUS 3 AND 6.3 X 10 MINUS 5 M, respectively. The enzymatic reaction was inhibited by the addition of ADP, but not by AMP. This suggests that the product fromATPin the reaction is composed of ADP PLUS Pi. Thus, it is proposed that this enzyme catalyzed the following reaction: (see article).", "contents": "Purification and properties of the dihydrofolate synthetase from pea seedlings. Dihydrofolate synthetase [EC 6.3.2.12] was extracted from the cell particles (mitochondrial fraction) of pea seedlings and purified about 2,000-fold by ammonium sulfate fraction, DEAE-cellulose column chromatography, Sephades G-200 gel filtration, and hydroxylapatite column chromatography. The enzyme preparation obtained was confirmed ultracentrifugally to be in the homogeneous state. The sedimentation coefficient of this enzyme was calculated as 3.9S. The apparent molecular weight of the enzyme was determined to be about 56,000. Optimum pH for the reaction was 8.8. The enzymatic reaction required dihydropteroate, L-glutamate and ATP as substrates, and divalent (Mg2+ or Mn 2+) and univalent K+, NH4+ OR Rb+) cations as cofactors. The enzyme was specific for dihydropteroic acid as the substrate. ATP was not replaceable with any other nucleotides. Km values for dihydropteroate, L-glutamate, ATP, Mg2+, and Mn2+ were 1.0 X 10 MINUS 6, 1.5 X 10 MINUS 3, 1.0 X 10 MINUS 4, 1.1 X 10 MINUS 3 AND 6.3 X 10 MINUS 5 M, respectively. The enzymatic reaction was inhibited by the addition of ADP, but not by AMP. This suggests that the product fromATPin the reaction is composed of ADP PLUS Pi. Thus, it is proposed that this enzyme catalyzed the following reaction: (see article)."}
{"id": "PMID:239105", "title": "Purification and properties of thiamine pyrophosphokinase from parsely leaf.", "content": "Thiamine pyrophosphokinase was purified about 8,000-fold from extracts of parsely leaves. The enzyme, as prepared, was homogenous on polyacrylamide gel electrophoresis. The molecular weight of the enzyme, estimated by gel filtration with Sephadex G-150, was approximately 30,000. In 0.05 M Tris-HCl, the enzymic activity showed a pH optimum over a range of 8 to 9. A least squares analyses of Lineweaver-Burk and Hofstee plots gave Km values of 0.8mM and 0.15mum for ATP and thiamine, respectively. Thiamine homologues and analogues so far tested, except for cetyl thiamine, were all inactive as substrates. The enzyme was specific for ATP and Mg++, although to a lesser extent a combination with other ribonucleoside triphosphates or divalent cations could replace them. SH reagents, such as PCMB, NEM and iodoacetamide, were potent inhibitors of the enzyme. The inhibition was prevented by the addition of dithiothreitol. Inorganic pyrophosphate exhibited striking inhibition. TMP could not replace thiamine as the substrate, whereas it inhibited the TPP formation from thiamine. These findings are consistent with the views that TMP is not directly converted to TPP but after being dephosphorylated by the action of a monoesterase, thiamine is pyrophosphorylated with ATP by thiamine pyrophosphokinase (EC 2.7.6.2) to form TPP and thus give a clear evidence regarding the mechanism of TPP formation in plant tissues.", "contents": "Purification and properties of thiamine pyrophosphokinase from parsely leaf. Thiamine pyrophosphokinase was purified about 8,000-fold from extracts of parsely leaves. The enzyme, as prepared, was homogenous on polyacrylamide gel electrophoresis. The molecular weight of the enzyme, estimated by gel filtration with Sephadex G-150, was approximately 30,000. In 0.05 M Tris-HCl, the enzymic activity showed a pH optimum over a range of 8 to 9. A least squares analyses of Lineweaver-Burk and Hofstee plots gave Km values of 0.8mM and 0.15mum for ATP and thiamine, respectively. Thiamine homologues and analogues so far tested, except for cetyl thiamine, were all inactive as substrates. The enzyme was specific for ATP and Mg++, although to a lesser extent a combination with other ribonucleoside triphosphates or divalent cations could replace them. SH reagents, such as PCMB, NEM and iodoacetamide, were potent inhibitors of the enzyme. The inhibition was prevented by the addition of dithiothreitol. Inorganic pyrophosphate exhibited striking inhibition. TMP could not replace thiamine as the substrate, whereas it inhibited the TPP formation from thiamine. These findings are consistent with the views that TMP is not directly converted to TPP but after being dephosphorylated by the action of a monoesterase, thiamine is pyrophosphorylated with ATP by thiamine pyrophosphokinase (EC 2.7.6.2) to form TPP and thus give a clear evidence regarding the mechanism of TPP formation in plant tissues."}
{"id": "PMID:239108", "title": "Renal tubular acidosis and skeletal demineralization in patients on long-term anticonvulsant therapy.", "content": "Three children ranging from seven to 12 years of age from unrelated families were given long-term anticonvulsant therapy including acetazolamide (Diamox). These children had rickets and renal tubular acidosis. Investigations have suggested (1) secondary hyperparathyroidism due to hypocalcemia of rickets and (2) prolonged acetazolamide therapy were responsible for acidosis as a result of reduction of bicarbonate reabsorption in the kidney. A clear-cut recovery from acidosis and rickets was seen in two patients following medication with high doses of vitamin D, an oral supplement of phosphorus, and discontinuance of acetazolamide therapy.", "contents": "Renal tubular acidosis and skeletal demineralization in patients on long-term anticonvulsant therapy. Three children ranging from seven to 12 years of age from unrelated families were given long-term anticonvulsant therapy including acetazolamide (Diamox). These children had rickets and renal tubular acidosis. Investigations have suggested (1) secondary hyperparathyroidism due to hypocalcemia of rickets and (2) prolonged acetazolamide therapy were responsible for acidosis as a result of reduction of bicarbonate reabsorption in the kidney. A clear-cut recovery from acidosis and rickets was seen in two patients following medication with high doses of vitamin D, an oral supplement of phosphorus, and discontinuance of acetazolamide therapy."}
{"id": "PMID:239109", "title": "Immediate effects of alkaline infusion in infants with respiratory distress syndrome.", "content": "Nineteen infants with acidosis associated with RDS were studied following the infusion of: (1) 0.58M (7%) THAM over 30 seconds; (2) molar bicarbonate over 30 seconds; (3) molar bicarbonate over 2 minutes; and (4) molar bicarbonate over 5 minutes. PaC02 fell after THAM; PaC02 rose sharply after bicarbonate and remained elevated 10 minutes after infusion. The pH rose abruptly in all infants and remained significantly elevated 10 minutes after infusion. Pa02 changes were variable; no infant had immediate improvement in Pa02. The changes in osmolality, hematocrit, and colloid osmotic pressure describe the immediate osmotic hemodilution following the infusion of hypertonic base.", "contents": "Immediate effects of alkaline infusion in infants with respiratory distress syndrome. Nineteen infants with acidosis associated with RDS were studied following the infusion of: (1) 0.58M (7%) THAM over 30 seconds; (2) molar bicarbonate over 30 seconds; (3) molar bicarbonate over 2 minutes; and (4) molar bicarbonate over 5 minutes. PaC02 fell after THAM; PaC02 rose sharply after bicarbonate and remained elevated 10 minutes after infusion. The pH rose abruptly in all infants and remained significantly elevated 10 minutes after infusion. Pa02 changes were variable; no infant had immediate improvement in Pa02. The changes in osmolality, hematocrit, and colloid osmotic pressure describe the immediate osmotic hemodilution following the infusion of hypertonic base."}
{"id": "PMID:239112", "title": "The determination of thebaine in Papaver bracteatum Lindl by gas-liquid chromatography.", "content": "Several solvents have been examined in the process of developing a convenient method for extracting powdered material and removing interfering pigments to produce an extract of Papaver bracteatum suitable for g.l.c. assay. The most suitable extracting solvent was aqueous acetic acid (5%); the assay method gave satisfactory reproducibility with a wide range of plant materials (coefficient of variation 0.63 to 3.33%). The accuracy was checked by recovery experiments with pure thebaine and by examination of exhausted marcs. The presence of other alkaloids did not interfer with the assay. There were substantial differences in the amounts of thebaine extracted from capsule and root samples by ammoniacal methanol and by aqueous acetic acid, indicating the presence of thebaine in a \"bound\" form. The minimum amount of thebaine that could readily be determined by the g.l.c. method was 0.3 mg in the sample of powder used for the assay.", "contents": "The determination of thebaine in Papaver bracteatum Lindl by gas-liquid chromatography. Several solvents have been examined in the process of developing a convenient method for extracting powdered material and removing interfering pigments to produce an extract of Papaver bracteatum suitable for g.l.c. assay. The most suitable extracting solvent was aqueous acetic acid (5%); the assay method gave satisfactory reproducibility with a wide range of plant materials (coefficient of variation 0.63 to 3.33%). The accuracy was checked by recovery experiments with pure thebaine and by examination of exhausted marcs. The presence of other alkaloids did not interfer with the assay. There were substantial differences in the amounts of thebaine extracted from capsule and root samples by ammoniacal methanol and by aqueous acetic acid, indicating the presence of thebaine in a \"bound\" form. The minimum amount of thebaine that could readily be determined by the g.l.c. method was 0.3 mg in the sample of powder used for the assay."}
{"id": "PMID:239113", "title": "Comparison of the nuclear magnetic resonance and infrared spectroscopic methods for the quantitative analysis of polydimethylsiloxane.", "content": "A method based on nuclear magnetic resonance spectroscopy is described for the quantitative determination of polyimethylsiloxane (PMS) in a variety of pharmaceutical preparations. An extraction procedure using deuterochloroform within the sample tube was devised. In the presence of an internal standard, the PMS concentration was determined directly using integrated peak areas, without the necessity of establishing calibration curves. Accurate quantitative results were achieved with sample, containing at least 2mg PMS, extracted from formulations containing greater than 0.5% PMS. The extraction procedure and nmr assay were both more efficient and convenient than the B.P.C. method.", "contents": "Comparison of the nuclear magnetic resonance and infrared spectroscopic methods for the quantitative analysis of polydimethylsiloxane. A method based on nuclear magnetic resonance spectroscopy is described for the quantitative determination of polyimethylsiloxane (PMS) in a variety of pharmaceutical preparations. An extraction procedure using deuterochloroform within the sample tube was devised. In the presence of an internal standard, the PMS concentration was determined directly using integrated peak areas, without the necessity of establishing calibration curves. Accurate quantitative results were achieved with sample, containing at least 2mg PMS, extracted from formulations containing greater than 0.5% PMS. The extraction procedure and nmr assay were both more efficient and convenient than the B.P.C. method."}
{"id": "PMID:239114", "title": "A model for steroid transport across biological membranes.", "content": "The absorption of a range of steroids (water soluble to lipid soluble) in the mouth was investigated under standard conditions and using gas chromatography. A two-compartment open model was used to describe the absorption of these steroids into, and through, the membrane. Rate constants were calculated on this basis using a feathering technique, and were used in an analogue computer program to predict steroid concentration which agree favourably with experimental data. Correlations between absorption and partition data were made in an attempt to relate the proposed model to anatomical features of the absorptive membrane and to make comparison with models proposed to describe drug absorption across the intestinal mucosa.", "contents": "A model for steroid transport across biological membranes. The absorption of a range of steroids (water soluble to lipid soluble) in the mouth was investigated under standard conditions and using gas chromatography. A two-compartment open model was used to describe the absorption of these steroids into, and through, the membrane. Rate constants were calculated on this basis using a feathering technique, and were used in an analogue computer program to predict steroid concentration which agree favourably with experimental data. Correlations between absorption and partition data were made in an attempt to relate the proposed model to anatomical features of the absorptive membrane and to make comparison with models proposed to describe drug absorption across the intestinal mucosa."}
{"id": "PMID:239115", "title": "Factors influencing the excretion and relative physiological availability of pethidine in man.", "content": "Factors influencing the urinary excretion of pethidine, norpethidine and pethidine N-oxide have been examined. The proportion of a dose of pethidine excreted unchanged or as norpethidine depends on the urinary pH and the route of administration. Older people appear to metabolize more of the drug and therefore excrete less unchanged pethidine. The rate of excretion of pethidine in acid urine is directly proportional to the plasma pethidine concentration and under these conditions the relative physiological availability of pethidine has been determined. It has not been possible to explain variations in the amount of pethidine excreted as the N-oxide.", "contents": "Factors influencing the excretion and relative physiological availability of pethidine in man. Factors influencing the urinary excretion of pethidine, norpethidine and pethidine N-oxide have been examined. The proportion of a dose of pethidine excreted unchanged or as norpethidine depends on the urinary pH and the route of administration. Older people appear to metabolize more of the drug and therefore excrete less unchanged pethidine. The rate of excretion of pethidine in acid urine is directly proportional to the plasma pethidine concentration and under these conditions the relative physiological availability of pethidine has been determined. It has not been possible to explain variations in the amount of pethidine excreted as the N-oxide."}
{"id": "PMID:239116", "title": "The role of dopamine and noradrenaline in temperature control of normal and reserpine-pretreated mice.", "content": "Drugs with the common property of stimulating dopamine receptors, have been tested for their effects on core temperature in control and reserpine-pretreated mice. Apomorphine, amantadine, amphetamine, L-dopa and atropine all produced a fall in mouse oesophageal temperature, their efficacy correlating with their ability to activate central dopamine receptors. Amphetamine and L-dopa had a biphasic effect the initial fall being followed by a rise. In reserpine-pretreated mice only amphetamine, apomorphine, L-dopa and D.L-threo-dihydroxyphenyl-serine effectively reversed hypothermia. Amphetamine had the highest efficacy of all the drugs tested. The sum of the effects of apomorphine and D.L-threo-dihydroxyphenylserine was equivalent to the effect of amphetamine alone. It is suggested that in control mice dopaminergic mechanisms mediate the hypothermia and noradrenergic mechanisms the hyperthermia. In reserpine-pretreated mice both systems are involved in the mechanisms restoring body temperature to normal.", "contents": "The role of dopamine and noradrenaline in temperature control of normal and reserpine-pretreated mice. Drugs with the common property of stimulating dopamine receptors, have been tested for their effects on core temperature in control and reserpine-pretreated mice. Apomorphine, amantadine, amphetamine, L-dopa and atropine all produced a fall in mouse oesophageal temperature, their efficacy correlating with their ability to activate central dopamine receptors. Amphetamine and L-dopa had a biphasic effect the initial fall being followed by a rise. In reserpine-pretreated mice only amphetamine, apomorphine, L-dopa and D.L-threo-dihydroxyphenyl-serine effectively reversed hypothermia. Amphetamine had the highest efficacy of all the drugs tested. The sum of the effects of apomorphine and D.L-threo-dihydroxyphenylserine was equivalent to the effect of amphetamine alone. It is suggested that in control mice dopaminergic mechanisms mediate the hypothermia and noradrenergic mechanisms the hyperthermia. In reserpine-pretreated mice both systems are involved in the mechanisms restoring body temperature to normal."}
{"id": "PMID:239117", "title": "Investigation of changes in the lipid content of guinea-pig lung after anaphylaxis.", "content": "A detailed analysis of the lipid content of guinea-pig lung following anaphylaxis in vivo induced by aerosolized antigen showed a significant reduction in all fractions. Anoxia induced by nitrogen produced reductions in the partial glycerides and ethanolamine phospholipid. Exposure to an aerosol of histamine caused a reduction in all but the choline phospholipid and sphingolipid fractions. It was concluded that the losses of choline phospholipid and sphingolipid result from the anaphylactic reaction and not from subsequent changes.", "contents": "Investigation of changes in the lipid content of guinea-pig lung after anaphylaxis. A detailed analysis of the lipid content of guinea-pig lung following anaphylaxis in vivo induced by aerosolized antigen showed a significant reduction in all fractions. Anoxia induced by nitrogen produced reductions in the partial glycerides and ethanolamine phospholipid. Exposure to an aerosol of histamine caused a reduction in all but the choline phospholipid and sphingolipid fractions. It was concluded that the losses of choline phospholipid and sphingolipid result from the anaphylactic reaction and not from subsequent changes."}
{"id": "PMID:239118", "title": "Release of adrenaline by anaphylaxis in the guinea-pig: its effect on lung lipid content.", "content": "The study was undertaken to discover whether the catecholamines released as a result of the stress and hypoxia of anaphylaxis were responsible for the concomitant loss of lipid from the lung. A method is described whereby the respiratory rate and volume and heart-rate of conscious sensitized guinea-pig were measured and the electrocardiogram recorded during anaphylaxis induced by aerosolized antigen. After 7 days or more, some animals were anaesthetized with pentobarbitone and respiration was artificially maintained at the level recorded in the conscious state, whilst the quantity of catecholamines liberated during anaphylaxis was assayed using an extra-corporeal blood circulation to superfuse smooth muscle preparations. In other animals of the same group, it was shown that intravenous infusion of adrenaline in a similar quantity to that detected in the circulation following anaphylaxis (0.3 mug min-(-1) for 40 min) caused losses of triglyceride and partial glycerides from the lungs. Thus, the loss of choline-containing phospholipid was attributed to the direct effects of the anaphylactic reaction on the lung tissue.", "contents": "Release of adrenaline by anaphylaxis in the guinea-pig: its effect on lung lipid content. The study was undertaken to discover whether the catecholamines released as a result of the stress and hypoxia of anaphylaxis were responsible for the concomitant loss of lipid from the lung. A method is described whereby the respiratory rate and volume and heart-rate of conscious sensitized guinea-pig were measured and the electrocardiogram recorded during anaphylaxis induced by aerosolized antigen. After 7 days or more, some animals were anaesthetized with pentobarbitone and respiration was artificially maintained at the level recorded in the conscious state, whilst the quantity of catecholamines liberated during anaphylaxis was assayed using an extra-corporeal blood circulation to superfuse smooth muscle preparations. In other animals of the same group, it was shown that intravenous infusion of adrenaline in a similar quantity to that detected in the circulation following anaphylaxis (0.3 mug min-(-1) for 40 min) caused losses of triglyceride and partial glycerides from the lungs. Thus, the loss of choline-containing phospholipid was attributed to the direct effects of the anaphylactic reaction on the lung tissue."}
{"id": "PMID:239119", "title": "The effect of acute bilateral adrenalectomy on vasopressor responses to catecholamines in dogs.", "content": "The effect of acute bilateral adrenalectomy on the pressor responses to adrenaline, noradrenaline and isoprenaline was studied in anaesthetized dogs. The responses to all the three catecholamines were reduced by adrenalectomy. Treatment with cortisone, cyclic AMP partially restored the responsiveness. Desocycorticosterone, aldosterone, hydrocortisone, phenylbutazone or infusion of either saline and noradrenaline failed to improve the impaired pressor responses seen in adrenalectomized dogs. Treatment with corticosterone alone. combined administration of aldosterone and hydrocortisone or cortisone followed by cyclic 3',5'-AMP also restored catecholamine responses amost to normal. The pressor responses to catecholmaines in dogs were also reduced by metyrapone-induced cortical insufficiency. Administration of corticosterone, cortisone or cyclic AMP slightly improved these responses; the recovery was not, however, as effective as that noted in the adrenalectomized condition.", "contents": "The effect of acute bilateral adrenalectomy on vasopressor responses to catecholamines in dogs. The effect of acute bilateral adrenalectomy on the pressor responses to adrenaline, noradrenaline and isoprenaline was studied in anaesthetized dogs. The responses to all the three catecholamines were reduced by adrenalectomy. Treatment with cortisone, cyclic AMP partially restored the responsiveness. Desocycorticosterone, aldosterone, hydrocortisone, phenylbutazone or infusion of either saline and noradrenaline failed to improve the impaired pressor responses seen in adrenalectomized dogs. Treatment with corticosterone alone. combined administration of aldosterone and hydrocortisone or cortisone followed by cyclic 3',5'-AMP also restored catecholamine responses amost to normal. The pressor responses to catecholmaines in dogs were also reduced by metyrapone-induced cortical insufficiency. Administration of corticosterone, cortisone or cyclic AMP slightly improved these responses; the recovery was not, however, as effective as that noted in the adrenalectomized condition."}
{"id": "PMID:239120", "title": "An anomalous effect of the intermediate products of riboflavine photolysis on the intestinal absorption of poorly absorbed water-solbule drug in rats.", "content": "The influence of the intermediate products of riboflavine photolysis on the absorption of poorly absorbed water-soluble drugs from the rat small intestine has been examined using an in situ recirculation technique. The absorption of phenol red, bromphenol blue (BPB) and their biliary excretion, and lactose isonicotinoyl-hydrazone (lactose-INH) and its plasma concentration were increased in experiments made in the presence of light in contrast to other made in the dark. The absorption of both phenol red and lactose-INH were concentration-dependent. On the other hand, a saturation phenomenon was demonstrated when the concentration of phenol red was kept constant while that of the water-soluble compound flavine mononucleotide (FMN) was changed. The results which were obtained from pretreatment experiments suggest an alteration in the permeability of the intestinal membrane. No enhancement effect could be demonstrated for lumichrome in the presence of absence of light.", "contents": "An anomalous effect of the intermediate products of riboflavine photolysis on the intestinal absorption of poorly absorbed water-solbule drug in rats. The influence of the intermediate products of riboflavine photolysis on the absorption of poorly absorbed water-soluble drugs from the rat small intestine has been examined using an in situ recirculation technique. The absorption of phenol red, bromphenol blue (BPB) and their biliary excretion, and lactose isonicotinoyl-hydrazone (lactose-INH) and its plasma concentration were increased in experiments made in the presence of light in contrast to other made in the dark. The absorption of both phenol red and lactose-INH were concentration-dependent. On the other hand, a saturation phenomenon was demonstrated when the concentration of phenol red was kept constant while that of the water-soluble compound flavine mononucleotide (FMN) was changed. The results which were obtained from pretreatment experiments suggest an alteration in the permeability of the intestinal membrane. No enhancement effect could be demonstrated for lumichrome in the presence of absence of light."}
{"id": "PMID:239132", "title": "Pharmacokinetics of haloalkylamines: cyclization and distribution in blood in vitro and in vivo.", "content": "The cyclization of N-(5-chloropentyl)-N-methylaminoaceto-2,6-xylidide hydrochloride (RAD 150) and N-(5-bromopentyl)-N-methylamino-aceto-2,6-xylide hydrobromide (RAD 154) in red blood cells of rats and rabbits was examined under in vitro and in vivo conditions. The rate of cyclization was much slower in plasma and blood than in a buffer solution, probably due to influence of protein binding of the compounds. The tertiary amines disappeared rapidly from the blood cells in vitro and in vivo and the piperidinium derivative (RAD 179) formed from the haloalkylamines disappeared almost as rapidly as the tertiary amines from the plasma in vivo. In contrast, the efflux of RAD 179 formed in the blood cells was slow (T 1/2 for rabbit erythrocytes: 9 h in vitro; 8 h in vivo) following a 1st order reaction. RAD 179 itself was only to a small extent taken up in the blood cells.", "contents": "Pharmacokinetics of haloalkylamines: cyclization and distribution in blood in vitro and in vivo. The cyclization of N-(5-chloropentyl)-N-methylaminoaceto-2,6-xylidide hydrochloride (RAD 150) and N-(5-bromopentyl)-N-methylamino-aceto-2,6-xylide hydrobromide (RAD 154) in red blood cells of rats and rabbits was examined under in vitro and in vivo conditions. The rate of cyclization was much slower in plasma and blood than in a buffer solution, probably due to influence of protein binding of the compounds. The tertiary amines disappeared rapidly from the blood cells in vitro and in vivo and the piperidinium derivative (RAD 179) formed from the haloalkylamines disappeared almost as rapidly as the tertiary amines from the plasma in vivo. In contrast, the efflux of RAD 179 formed in the blood cells was slow (T 1/2 for rabbit erythrocytes: 9 h in vitro; 8 h in vivo) following a 1st order reaction. RAD 179 itself was only to a small extent taken up in the blood cells."}
{"id": "PMID:239133", "title": "Skin irritants of Euphorbia fortissima.", "content": "By means of a combination of partition and chromatographic methods six irritant constituents were isolated from the fresh latex of Euphorbia fortissima. Compounds A-D were di-esters of the common parent diterpene 12-deoxyphorbol, and compounds E and F were mono-esters of the same diterpene. The fresh latex had an irritant dose 50% (ID50) on mice of 0-64 mug mul- minus 1. Compounds A-D are short-acting irritants reaching a maximum activity within 4 h of application to the skin, whilst the monoesters maintained potent irritant effects for up to 24 h. Selective hydrolysis of the di-esters at the C-20 primary ester group also produced mono-esters of greater potency after 24 h. An increase in the length of the fatty acid located at C-13 produced greater biological activity in both the mono- and di-ester groups.", "contents": "Skin irritants of Euphorbia fortissima. By means of a combination of partition and chromatographic methods six irritant constituents were isolated from the fresh latex of Euphorbia fortissima. Compounds A-D were di-esters of the common parent diterpene 12-deoxyphorbol, and compounds E and F were mono-esters of the same diterpene. The fresh latex had an irritant dose 50% (ID50) on mice of 0-64 mug mul- minus 1. Compounds A-D are short-acting irritants reaching a maximum activity within 4 h of application to the skin, whilst the monoesters maintained potent irritant effects for up to 24 h. Selective hydrolysis of the di-esters at the C-20 primary ester group also produced mono-esters of greater potency after 24 h. An increase in the length of the fatty acid located at C-13 produced greater biological activity in both the mono- and di-ester groups."}
{"id": "PMID:239134", "title": "Metabolism of phenothiazines: identification of N-oxygenated products by gas chromatography and mass spectrometry.", "content": "The solid inlet mass spectra of the N-oxide and N-oxide sulphoxide metabolites of promazine, chlorpromazine and methotrimeprazine have been determined at different temperatures and compared with the mass spectra of the main thermolytic product of the N-oxides and N-oxide sulphoxides obtained during combined gas chromatography-mass spectrometry. Diagnostic ions were produced by direct insertion of the compounds at ambient temperature into the mass spectrometer. These ions distinguish the N-oxides of arylalkyl tertiary amines from the N-oxygenated derivatives of primary and secondary arylalkylamines.", "contents": "Metabolism of phenothiazines: identification of N-oxygenated products by gas chromatography and mass spectrometry. The solid inlet mass spectra of the N-oxide and N-oxide sulphoxide metabolites of promazine, chlorpromazine and methotrimeprazine have been determined at different temperatures and compared with the mass spectra of the main thermolytic product of the N-oxides and N-oxide sulphoxides obtained during combined gas chromatography-mass spectrometry. Diagnostic ions were produced by direct insertion of the compounds at ambient temperature into the mass spectrometer. These ions distinguish the N-oxides of arylalkyl tertiary amines from the N-oxygenated derivatives of primary and secondary arylalkylamines."}
{"id": "PMID:239135", "title": "Metabolism of quinalbarbitone.", "content": "The human metabolism of (+/-)-5-allyl-5-(1'-methylbutyl) barbituric acid (I), quinalbarbitone, taken orally, has been studied. Comparison of g.c. and g.c.-m.s. data from derivatized extracts of urine with similar data from synthetic samples confirmed the presence of the two diastereoisomeric forms of 5-allyl-5-(3'hydroxy-1'-methylbutyl)barbituric acid (II), 5-allyl-5-(3'-oxo-1'-methylbutyl)barbituric acid (III), 5-allyl-5-(1'-methyl-3'-carboxypropyl)barbituric acid (IV), and 5-(2',3'-dihydroxypropyl)-5-(1'-methylbutyl)barbituric acid (V) in the urine. There was no evidence for the urinary excretion of unchanged drug. The rate of excretion of these metabolites has been examined in some detail, and rate-limited kinetics shown to apply for excretion of the acid (IV) and the diol (V).", "contents": "Metabolism of quinalbarbitone. The human metabolism of (+/-)-5-allyl-5-(1'-methylbutyl) barbituric acid (I), quinalbarbitone, taken orally, has been studied. Comparison of g.c. and g.c.-m.s. data from derivatized extracts of urine with similar data from synthetic samples confirmed the presence of the two diastereoisomeric forms of 5-allyl-5-(3'hydroxy-1'-methylbutyl)barbituric acid (II), 5-allyl-5-(3'-oxo-1'-methylbutyl)barbituric acid (III), 5-allyl-5-(1'-methyl-3'-carboxypropyl)barbituric acid (IV), and 5-(2',3'-dihydroxypropyl)-5-(1'-methylbutyl)barbituric acid (V) in the urine. There was no evidence for the urinary excretion of unchanged drug. The rate of excretion of these metabolites has been examined in some detail, and rate-limited kinetics shown to apply for excretion of the acid (IV) and the diol (V)."}
{"id": "PMID:239136", "title": "The diffusion of penicillin G and ampicillin through phospholipid sols.", "content": "The self-diffusion coefficients of penicillin G and ampicillin have been determined at 25 degrees in water and in the presence of a swamping concentration of electrolyte. The antibiotics diffused through phospholipid dispersions at a reduced rate due to interaction with the lipid aggregates. Ampicillin diffused through the phosphatidylcholine and phosphatidylethanolamine dispersions more rapidly than penicillin G, whereas the latter diffused more rapidly through the lysophosphatidylcholine dispersions. Estimates of binding have been made from these data and compared with those obtained from equilibrium dialysis studies. Surface tension measurements indicated that the antibiotics exhibited minimal surface activity. These results have been correlated with data obtained in other studies and a possible explanation has been advanced for the reported differences in vivo activity of penicillin G and ampicillin.", "contents": "The diffusion of penicillin G and ampicillin through phospholipid sols. The self-diffusion coefficients of penicillin G and ampicillin have been determined at 25 degrees in water and in the presence of a swamping concentration of electrolyte. The antibiotics diffused through phospholipid dispersions at a reduced rate due to interaction with the lipid aggregates. Ampicillin diffused through the phosphatidylcholine and phosphatidylethanolamine dispersions more rapidly than penicillin G, whereas the latter diffused more rapidly through the lysophosphatidylcholine dispersions. Estimates of binding have been made from these data and compared with those obtained from equilibrium dialysis studies. Surface tension measurements indicated that the antibiotics exhibited minimal surface activity. These results have been correlated with data obtained in other studies and a possible explanation has been advanced for the reported differences in vivo activity of penicillin G and ampicillin."}
{"id": "PMID:239137", "title": "The instrumentation of a Zanasi LZ/64 capsule filling machine.", "content": "The dosator system of a Zanasi LZ/64 capsule filling machine was modified and strain gauges were fitted. These were used to measure the forces on the powder being filled during compaction and ejection. The patterns of those forces produced were shown to differ between different materials and between lubricated and unlubricated materials. Tentative reasons for the observed differences have been suggested.", "contents": "The instrumentation of a Zanasi LZ/64 capsule filling machine. The dosator system of a Zanasi LZ/64 capsule filling machine was modified and strain gauges were fitted. These were used to measure the forces on the powder being filled during compaction and ejection. The patterns of those forces produced were shown to differ between different materials and between lubricated and unlubricated materials. Tentative reasons for the observed differences have been suggested."}
{"id": "PMID:239149", "title": "The development of a radioimmunoassay for cannabinoids in blood and urine.", "content": "Antibodies, for use in radioimmunoassay, have been raised in sheep by immunization with a conjugate of delta9-tetrahydrocannabinol hemisuccinate and bovine serum albumin. Antiserum titre and avidity were increased by successive booster doses of conjugate. The high degree of non-specific binding encountered in the radioimmunoassay of cannabinoids was reduced by the use of the solubilizing detergent Triton X-405 and by restricting protein concentration in the assay medium. Plasma samples were deproteinized with ethanol before assay, but urine was directly assayed. High avidity antibodies and high specific activity [3H]-delta9-tetrahydrocannabinol permitted the detection of 50 pg of cross-reacting cannabinoids--a sensitivity of 7-5 ng ml-1 of plasma and 1-0 ng ml-1 of urine. Whilst apparently specific for the three-ringed cannabinoid nucleus, the assay antiserum cross-reacted with several cannabinoids, both natural compounds and metabolites. Partial identification of cross-reacting cannabinoids was achieved by the use of pure compounds and by the assay of plasma and urine samples collected from rabbits given pure cannabinoids intravenously.", "contents": "The development of a radioimmunoassay for cannabinoids in blood and urine. Antibodies, for use in radioimmunoassay, have been raised in sheep by immunization with a conjugate of delta9-tetrahydrocannabinol hemisuccinate and bovine serum albumin. Antiserum titre and avidity were increased by successive booster doses of conjugate. The high degree of non-specific binding encountered in the radioimmunoassay of cannabinoids was reduced by the use of the solubilizing detergent Triton X-405 and by restricting protein concentration in the assay medium. Plasma samples were deproteinized with ethanol before assay, but urine was directly assayed. High avidity antibodies and high specific activity [3H]-delta9-tetrahydrocannabinol permitted the detection of 50 pg of cross-reacting cannabinoids--a sensitivity of 7-5 ng ml-1 of plasma and 1-0 ng ml-1 of urine. Whilst apparently specific for the three-ringed cannabinoid nucleus, the assay antiserum cross-reacted with several cannabinoids, both natural compounds and metabolites. Partial identification of cross-reacting cannabinoids was achieved by the use of pure compounds and by the assay of plasma and urine samples collected from rabbits given pure cannabinoids intravenously."}
{"id": "PMID:239150", "title": "Prostaglandins and the anti-inflammatory activities of aspirin and sodium salicylate.", "content": "Acetylsalicylic acid (aspirin) and sodium salicylate are equally effective in reducing the swelling in the carrageenan-induced paw test and the accumulation of leucocytes into the inflammatory exudate produced by the subcutaneous implantation of polyvinyl sponges in the rat. Aspirin but not sodium salicylate caused a significant reduction in the potentiation of paw oedema found after the concurrent administration of carrageenan and arachidonic acid. Some implications of these findings are discussed.", "contents": "Prostaglandins and the anti-inflammatory activities of aspirin and sodium salicylate. Acetylsalicylic acid (aspirin) and sodium salicylate are equally effective in reducing the swelling in the carrageenan-induced paw test and the accumulation of leucocytes into the inflammatory exudate produced by the subcutaneous implantation of polyvinyl sponges in the rat. Aspirin but not sodium salicylate caused a significant reduction in the potentiation of paw oedema found after the concurrent administration of carrageenan and arachidonic acid. Some implications of these findings are discussed."}
{"id": "PMID:239151", "title": "The surface activity of the alveolar lining layer of guinea-pig lung following anaphylaxis.", "content": "The surface activity and lipid composition of alveolar extracts of guinea-pig lung following anaphylaxis have been studied. The extracts showed a reduced ability to lower surface tension on compression of the surface film which was maximal 30 min after challenge. No significant changes in the lipid content were found but there was a marked increase in the soluble solids 10 min after anaphylactic shock. The significance of these findings is discussed.", "contents": "The surface activity of the alveolar lining layer of guinea-pig lung following anaphylaxis. The surface activity and lipid composition of alveolar extracts of guinea-pig lung following anaphylaxis have been studied. The extracts showed a reduced ability to lower surface tension on compression of the surface film which was maximal 30 min after challenge. No significant changes in the lipid content were found but there was a marked increase in the soluble solids 10 min after anaphylactic shock. The significance of these findings is discussed."}
{"id": "PMID:239152", "title": "Effects of thioridazine and diazepam on the pharmacokinetics of [14C]imipramine in rat: acute study.", "content": "The pharmacokinetics of [14C]imipramine (10 mg kg minus 1) were tested in male Wistar rats for interaction with thioridazine (16 mg kg minus 1) or diazepam (10 mg kg- minus 1). All drugs were administered orally with the test substances being given 40 min before [14C]imipramine dosing. Bile and urine were collected for 90 min after the radioactive drug was given. The animals were then killed and the tissues removed. Thioridazine reduced the excretion of radioactivity into the bile and urine, and increased the weight of the contents within the gastrointestinal tract. These effects were interpreted as being mainly due to a reduction in gastrointestinal motility resulting in a slower stomach emptying of [14C]imipramine. No effect on metabolism was detected. Diazepam pretreatment reduced the concentration ratio of radioactivity in the small intestinal contents to that of plasma, but did not alter the tissue distribution, metabolism or excretion of [14C]imipramine.", "contents": "Effects of thioridazine and diazepam on the pharmacokinetics of [14C]imipramine in rat: acute study. The pharmacokinetics of [14C]imipramine (10 mg kg minus 1) were tested in male Wistar rats for interaction with thioridazine (16 mg kg minus 1) or diazepam (10 mg kg- minus 1). All drugs were administered orally with the test substances being given 40 min before [14C]imipramine dosing. Bile and urine were collected for 90 min after the radioactive drug was given. The animals were then killed and the tissues removed. Thioridazine reduced the excretion of radioactivity into the bile and urine, and increased the weight of the contents within the gastrointestinal tract. These effects were interpreted as being mainly due to a reduction in gastrointestinal motility resulting in a slower stomach emptying of [14C]imipramine. No effect on metabolism was detected. Diazepam pretreatment reduced the concentration ratio of radioactivity in the small intestinal contents to that of plasma, but did not alter the tissue distribution, metabolism or excretion of [14C]imipramine."}
{"id": "PMID:239153", "title": "Characterization of an angiotensin II-fluorescamine derivative.", "content": "The coupling of fluorescamine (4-phenylspiro[furan-2(3H), 1'-PHTHALAN]-3,3'dione) to angiotensin II to form a fluorescent derivative was studied. Complete reaction of the peptide below concentrations of 10- minus 4 M could be achieved with a fluorescamine concentration of 0-3 mg ml- minus 1 of acetone at pH 8-3, and the lowest concentration detectable by fluorescence spectroscopy was 100 pmol ml- minus 1. The derivative, as prepared did not react with ninhydrin, and no fluorescence was generated when fluorescamine was reacted with (1-Sar)-ATII. These data suggest that fluorescence is generated only through the coupling of fluorescamine to the N-terminal primary amine of ATII. The ATII-fluorescamine derivative has the same intrinsic activity on the contraction of rat colon (elevenfold loss of affinity), and on the release of fluorogenic corticosteroids from bovine adrenal cortical slices (sixfold loss of affinity) compared to ATII. Water-hydrolysed fluorescamine and Asp-fluorescamine did not contract rat colon preparations; the contractile response to ATII-fluorescamine was blocked by (8-Leu)-ATII, a specific ATII antagonist. These findings suggest that theATII fluorophore shares a common receptor site with the native octapeptide. The rate loss of biological activity of the ATII-fluorescamine derivative was appreciably lower than that observed for ATII. The present study suggests that the ATII-fluorescamine derivative can be substituted for radioactively-labelled ATII for use in a variety of applications.", "contents": "Characterization of an angiotensin II-fluorescamine derivative. The coupling of fluorescamine (4-phenylspiro[furan-2(3H), 1'-PHTHALAN]-3,3'dione) to angiotensin II to form a fluorescent derivative was studied. Complete reaction of the peptide below concentrations of 10- minus 4 M could be achieved with a fluorescamine concentration of 0-3 mg ml- minus 1 of acetone at pH 8-3, and the lowest concentration detectable by fluorescence spectroscopy was 100 pmol ml- minus 1. The derivative, as prepared did not react with ninhydrin, and no fluorescence was generated when fluorescamine was reacted with (1-Sar)-ATII. These data suggest that fluorescence is generated only through the coupling of fluorescamine to the N-terminal primary amine of ATII. The ATII-fluorescamine derivative has the same intrinsic activity on the contraction of rat colon (elevenfold loss of affinity), and on the release of fluorogenic corticosteroids from bovine adrenal cortical slices (sixfold loss of affinity) compared to ATII. Water-hydrolysed fluorescamine and Asp-fluorescamine did not contract rat colon preparations; the contractile response to ATII-fluorescamine was blocked by (8-Leu)-ATII, a specific ATII antagonist. These findings suggest that theATII fluorophore shares a common receptor site with the native octapeptide. The rate loss of biological activity of the ATII-fluorescamine derivative was appreciably lower than that observed for ATII. The present study suggests that the ATII-fluorescamine derivative can be substituted for radioactively-labelled ATII for use in a variety of applications."}
{"id": "PMID:239154", "title": "Synthesis and characteristics of the enantiomers of the cyclic metabonate of methadone.", "content": "2-Ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (II), a cyclic metabonate of methadone was synthesized from methadone (I) and methadone-N-oxide (III). M-Chloroperbenzoic acid was used to oxidatively demethylate I while sulphur dioxide reductively demethylated III to give II. The importance of these syntheses lies in the fact that there is no attack on the asymmetric carbon atom in I or III, thus providing direct methods of obtaining the optical isomers of II.", "contents": "Synthesis and characteristics of the enantiomers of the cyclic metabonate of methadone. 2-Ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (II), a cyclic metabonate of methadone was synthesized from methadone (I) and methadone-N-oxide (III). M-Chloroperbenzoic acid was used to oxidatively demethylate I while sulphur dioxide reductively demethylated III to give II. The importance of these syntheses lies in the fact that there is no attack on the asymmetric carbon atom in I or III, thus providing direct methods of obtaining the optical isomers of II."}
{"id": "PMID:239155", "title": "The interaction of aminoalkylaminoanthraquinones with deoxyribonucleic acid.", "content": "A series of aminoalkylaminoanthraquinones have been prepared as potential intercalating agents. The binding to DNA of these compounds and the known intercalating drugs chloroquine, lucanthone, daunorubicin and doxorubicin has been characterized by spectrophotometric titration. The association constant for the interaction with DNA has been determined for each compound from a Scatchard plot. The compounds synthesized had association constants between 0-5 and 4-2 times 10(6) compared with 0-93, 0-90, 3-10 and 2-49 times 10(6) for chloroquine, lucanthone, daunorubicin and doxorubicin respectively.", "contents": "The interaction of aminoalkylaminoanthraquinones with deoxyribonucleic acid. A series of aminoalkylaminoanthraquinones have been prepared as potential intercalating agents. The binding to DNA of these compounds and the known intercalating drugs chloroquine, lucanthone, daunorubicin and doxorubicin has been characterized by spectrophotometric titration. The association constant for the interaction with DNA has been determined for each compound from a Scatchard plot. The compounds synthesized had association constants between 0-5 and 4-2 times 10(6) compared with 0-93, 0-90, 3-10 and 2-49 times 10(6) for chloroquine, lucanthone, daunorubicin and doxorubicin respectively."}
{"id": "PMID:239156", "title": "The effect of mucin on the bioavailability of tetracycline from the gastrointestinal tract; in vivo, in vitro correlations.", "content": "The bioavailability of tetracycline in the presence and absence of a porcine gastric mucin dispersion (1% W/V) has been studied by in vivo perfusion of the rat small intestine, the rat everted gut, a diffusion cell technique and the Sartorius Absorption Simulator Apparatus. In the presence of the mucin preparation an approximate 50% reduction in the numerical values of each of the parameters used to measure the tetracycline movement across the membrane was found. The physiological significance of each technique and the methods themselves are discussed. Interaction of tetracycline with the porcine gastric mucin preparation is considered in relation to the molecular structure of mucus. The results suggest the drug is bound in some way, as yet undefined, to the mucin macromolecule.", "contents": "The effect of mucin on the bioavailability of tetracycline from the gastrointestinal tract; in vivo, in vitro correlations. The bioavailability of tetracycline in the presence and absence of a porcine gastric mucin dispersion (1% W/V) has been studied by in vivo perfusion of the rat small intestine, the rat everted gut, a diffusion cell technique and the Sartorius Absorption Simulator Apparatus. In the presence of the mucin preparation an approximate 50% reduction in the numerical values of each of the parameters used to measure the tetracycline movement across the membrane was found. The physiological significance of each technique and the methods themselves are discussed. Interaction of tetracycline with the porcine gastric mucin preparation is considered in relation to the molecular structure of mucus. The results suggest the drug is bound in some way, as yet undefined, to the mucin macromolecule."}
{"id": "PMID:239157", "title": "A comparison of solute migration in a test granulation dried by fluidization and other methods.", "content": "The intragranular migration of sodium chloride in granules made by the wet massing of heavy kaolin B.P. with salt solution has been studied in batches dried by fluidization and a vacuum tumbling method. The larger granules from the fluidized batch exhibited considerable intragranular variation with the outer crust containing over twice the average salt concentration. Solute loss from this layer by abrasion on prolonged fluidization was slight but the dust eluted from the dryer had a salt content above average. Analysis of sieved fractions of the dust showed that this enrichment was concentrated in the fine material passing a 53 mum mesh. The vacuum dried granules had less migration and were less resistant to crushing than those dried by fluidization. The dust produced had a salt content only slightly greater than the average composition and the overall solute content of the sized fractions were all close to this average. The same system was used to study intergranular migration in a fixed bed when the granules were dried by infrared radiation, by microwave radiation, by convection from air and in a vacuum. The greatest migration occurred in samples dried by infrared radiation and the maximum solute concentration was near the middle of the bed. The air dried granules had less migration and the maximum concentration was in the surface layer. The granules dried in a vacuum and by microwave radiation were fairly uniform in composition throughout the bed. The above results are explained on the basis of the capillary theory of drying together with the modifying influence of the drying method on the probable heat and mass transfer rates.", "contents": "A comparison of solute migration in a test granulation dried by fluidization and other methods. The intragranular migration of sodium chloride in granules made by the wet massing of heavy kaolin B.P. with salt solution has been studied in batches dried by fluidization and a vacuum tumbling method. The larger granules from the fluidized batch exhibited considerable intragranular variation with the outer crust containing over twice the average salt concentration. Solute loss from this layer by abrasion on prolonged fluidization was slight but the dust eluted from the dryer had a salt content above average. Analysis of sieved fractions of the dust showed that this enrichment was concentrated in the fine material passing a 53 mum mesh. The vacuum dried granules had less migration and were less resistant to crushing than those dried by fluidization. The dust produced had a salt content only slightly greater than the average composition and the overall solute content of the sized fractions were all close to this average. The same system was used to study intergranular migration in a fixed bed when the granules were dried by infrared radiation, by microwave radiation, by convection from air and in a vacuum. The greatest migration occurred in samples dried by infrared radiation and the maximum solute concentration was near the middle of the bed. The air dried granules had less migration and the maximum concentration was in the surface layer. The granules dried in a vacuum and by microwave radiation were fairly uniform in composition throughout the bed. The above results are explained on the basis of the capillary theory of drying together with the modifying influence of the drying method on the probable heat and mass transfer rates."}
{"id": "PMID:239169", "title": "Dopamine receptor blockade and the neuroleptics, a crystallographic study.", "content": "The X-ray structures of 12 drugs of the tricyclic class having varying pharmacological profiles have been examined in detail in an attempt to rationalize the known structure-activity relations of neuroleptic drugs with respect to their ability to block dopamine receptors in the brain. Further evidence is presented in support of the theory that the neuroleptics are able to block dopamine receptors because of a conformational complementarity between certain portions of these drugs and dopamine.", "contents": "Dopamine receptor blockade and the neuroleptics, a crystallographic study. The X-ray structures of 12 drugs of the tricyclic class having varying pharmacological profiles have been examined in detail in an attempt to rationalize the known structure-activity relations of neuroleptic drugs with respect to their ability to block dopamine receptors in the brain. Further evidence is presented in support of the theory that the neuroleptics are able to block dopamine receptors because of a conformational complementarity between certain portions of these drugs and dopamine."}
{"id": "PMID:239170", "title": "The evidence of the release of prostaglandin-like material from rabbit kidney and guinea-pig lung by (minus)-trans-delta9-tetrahydrocannabinol.", "content": "Injection of (minus)-trans-delta9-tetrahydrocannabinol (THC) through the renal artery caused a decrease in perfusion pressure and an increase in urine produced by the isolated perfused rabbit kidney. Both effects of THC are inhibited by the prior addition of aspirin to the perfusion medium. THC also induced a dose-dependent increase in perfusion pressure on the isolated perfused lung of guinea-pig and the effluent from the lung produced a contraction on the isolated continuously superfused rat stomach fundus strip. These effects are prevented by the pretreatment of the lung with aspirin which inhibits the production of prostaglandins (PG) and SC 19220 which inhibits the pharmacological effects of PG.", "contents": "The evidence of the release of prostaglandin-like material from rabbit kidney and guinea-pig lung by (minus)-trans-delta9-tetrahydrocannabinol. Injection of (minus)-trans-delta9-tetrahydrocannabinol (THC) through the renal artery caused a decrease in perfusion pressure and an increase in urine produced by the isolated perfused rabbit kidney. Both effects of THC are inhibited by the prior addition of aspirin to the perfusion medium. THC also induced a dose-dependent increase in perfusion pressure on the isolated perfused lung of guinea-pig and the effluent from the lung produced a contraction on the isolated continuously superfused rat stomach fundus strip. These effects are prevented by the pretreatment of the lung with aspirin which inhibits the production of prostaglandins (PG) and SC 19220 which inhibits the pharmacological effects of PG."}
{"id": "PMID:239171", "title": "An improved implantation pellet for rapid induction of morphine dependence in mice.", "content": "A new type of morphine implantation pellet for the rapid induction of physical dependence in mice can be prepared by absorbing 7 mg morphine sulphate onto molecular sieves Type 4A (BDH). The small cylindrical pellets can be implanted subcutaneously without trauma and the need for anaesthesia, and are easily removed at any time from the animals. The peak of physical dependence is reached 24 h after implantation, and mortality is negligible. Withdrawal symptoms can be precipitated by intraperitoneal injection of naloxone, without removal of the pellet, and up to 70% of a group of mice show the characteristic urge to jump off a raised platform. This type of pellet has definite advantages over some other sustained-release preparations used in studies on morphine addiction in small animals.", "contents": "An improved implantation pellet for rapid induction of morphine dependence in mice. A new type of morphine implantation pellet for the rapid induction of physical dependence in mice can be prepared by absorbing 7 mg morphine sulphate onto molecular sieves Type 4A (BDH). The small cylindrical pellets can be implanted subcutaneously without trauma and the need for anaesthesia, and are easily removed at any time from the animals. The peak of physical dependence is reached 24 h after implantation, and mortality is negligible. Withdrawal symptoms can be precipitated by intraperitoneal injection of naloxone, without removal of the pellet, and up to 70% of a group of mice show the characteristic urge to jump off a raised platform. This type of pellet has definite advantages over some other sustained-release preparations used in studies on morphine addiction in small animals."}
{"id": "PMID:239172", "title": "The vascular changes after ephedrine tachyphylaxis.", "content": "The changes elicited after ephedrine tachyphylaxis in the dog femoral and rabbit aortic strips isolated from the untreated and ephedrine pre-treated animals have been studied. In untreated strips, ephedrine exhibited dose-dependent contractions which were blocked by phenoxybenzamine. These contractile responses to ephedrine were reduced after pre-treatment with ephedrine in vivo. In rabbit aortic strips previously contracted with noradrenaline or KCL, ephedrine induced dose-dependent relaxations at high concentrations, which were not affected by propranolol. These relaxation responses were likewise diminished after ephedrine. Dose-related contractile responses to noradrenaline were potentiated at low concentrations and depressed at high concentrations after ephedrine whereas those to adrenaline were inhibited over the entire agonist range. Responses to KCL were not affected. These reductions in the responses to noradrenaline and adrenaline after treatment with ephedrine in vivo were inhibited by icreased calcium2+ concentration. From the results, it can be presumed that the observed changes in vascular responsiveness may be partially involved in the development of ephedrine tachyphylaxis.", "contents": "The vascular changes after ephedrine tachyphylaxis. The changes elicited after ephedrine tachyphylaxis in the dog femoral and rabbit aortic strips isolated from the untreated and ephedrine pre-treated animals have been studied. In untreated strips, ephedrine exhibited dose-dependent contractions which were blocked by phenoxybenzamine. These contractile responses to ephedrine were reduced after pre-treatment with ephedrine in vivo. In rabbit aortic strips previously contracted with noradrenaline or KCL, ephedrine induced dose-dependent relaxations at high concentrations, which were not affected by propranolol. These relaxation responses were likewise diminished after ephedrine. Dose-related contractile responses to noradrenaline were potentiated at low concentrations and depressed at high concentrations after ephedrine whereas those to adrenaline were inhibited over the entire agonist range. Responses to KCL were not affected. These reductions in the responses to noradrenaline and adrenaline after treatment with ephedrine in vivo were inhibited by icreased calcium2+ concentration. From the results, it can be presumed that the observed changes in vascular responsiveness may be partially involved in the development of ephedrine tachyphylaxis."}
{"id": "PMID:239173", "title": "Chemical reactions involved in penicillin allergy: kinetics and mechanism of penicillin aminolysis.", "content": "In view of the fundamental importance of the reaction of penicillins with amino groups of proteins to the penicillin allergy, the aminolysis of benzylpenicillin by various amines was kinetically investigated. The formation rate constants, kamide, of benzylpenicilloylamides were determined at 35 degrees, 45 degrees and 60 degrees (mu equals 0.5), and found to obey the general rate law: kamide equals k1[amine] + k2[amine H+] [amine] + k3[amine]2 + k4[amine]aoh. All of the amines exhibited the unassisted nucleophilic rate constant, k1. The relative importance of the other kinetic terms depends on the basicity and the chemical structure of amines. The reaction mechanism of penicillin aminolysis was discussed. Bronsted relations for k1, k2 and k3, except for hydrazines, were satisfactory.", "contents": "Chemical reactions involved in penicillin allergy: kinetics and mechanism of penicillin aminolysis. In view of the fundamental importance of the reaction of penicillins with amino groups of proteins to the penicillin allergy, the aminolysis of benzylpenicillin by various amines was kinetically investigated. The formation rate constants, kamide, of benzylpenicilloylamides were determined at 35 degrees, 45 degrees and 60 degrees (mu equals 0.5), and found to obey the general rate law: kamide equals k1[amine] + k2[amine H+] [amine] + k3[amine]2 + k4[amine]aoh. All of the amines exhibited the unassisted nucleophilic rate constant, k1. The relative importance of the other kinetic terms depends on the basicity and the chemical structure of amines. The reaction mechanism of penicillin aminolysis was discussed. Bronsted relations for k1, k2 and k3, except for hydrazines, were satisfactory."}
{"id": "PMID:239174", "title": "Trialkylsily moieties as potential pharmacokinetic modifying groups for aminoalchohols.", "content": "Water soluble derivatives of the aminoalcohols methylephedrine, ephedrine and norephedrine have been synthesized to contain various trialkyl silyl groups attached to the hydroxyl group of the aminoalcohol hydrochloride. Variation of the alkyl substituents on the silyl group produces a wide variety of derivatives possessing differing lipid solubilities and rates of hydrolysis to the parent aminoalcohol.", "contents": "Trialkylsily moieties as potential pharmacokinetic modifying groups for aminoalchohols. Water soluble derivatives of the aminoalcohols methylephedrine, ephedrine and norephedrine have been synthesized to contain various trialkyl silyl groups attached to the hydroxyl group of the aminoalcohol hydrochloride. Variation of the alkyl substituents on the silyl group produces a wide variety of derivatives possessing differing lipid solubilities and rates of hydrolysis to the parent aminoalcohol."}
{"id": "PMID:239175", "title": "Dissolution and bioavailability of the anhydrate and trihydrate forms of ampicillin.", "content": "The solubilities and intrinsic dissolution rates of ampicillin anhydrate and trihydrate in distilled water and dilute hydrochloric acid at 37 degrees have been measured. The dissolution rates of these materials from loose filled hard gelatin capsules were determined and the in vivo bioavailabilities of the compounds compared. Small differences in the in vitro behaviour of the anhydrate and trihydrate forms were recorded but the in vivo availability of the two compounds was the same.", "contents": "Dissolution and bioavailability of the anhydrate and trihydrate forms of ampicillin. The solubilities and intrinsic dissolution rates of ampicillin anhydrate and trihydrate in distilled water and dilute hydrochloric acid at 37 degrees have been measured. The dissolution rates of these materials from loose filled hard gelatin capsules were determined and the in vivo bioavailabilities of the compounds compared. Small differences in the in vitro behaviour of the anhydrate and trihydrate forms were recorded but the in vivo availability of the two compounds was the same."}
{"id": "PMID:239176", "title": "The percutaneous absorption of phenolic compounds: the effect of vehicles on the penetration of phenol.", "content": "The effects of interactions between drug and skin, drug and vehicle, and vehicle and skin on the overall penetration rate of a drug through the skin may be evaluated by comparison of penetration rates through excised skin and an inert reference membrane such as polyethylene. Dimethyl sulphoxide, dimethyl formamide, ethanol and water increase the permeability of the skin but because of reduced thermodynamic activities in the vehicles low penetration rates are observed.", "contents": "The percutaneous absorption of phenolic compounds: the effect of vehicles on the penetration of phenol. The effects of interactions between drug and skin, drug and vehicle, and vehicle and skin on the overall penetration rate of a drug through the skin may be evaluated by comparison of penetration rates through excised skin and an inert reference membrane such as polyethylene. Dimethyl sulphoxide, dimethyl formamide, ethanol and water increase the permeability of the skin but because of reduced thermodynamic activities in the vehicles low penetration rates are observed."}
{"id": "PMID:239188", "title": "Development and evaluation of a dexamethasone timed-release aerosol formulation.", "content": "Dexamethasone microcapcules were prepared and in vitro parameters were determined by sieve analysis which yielded materials retained on Nos. 80-, 100-, 200-, and 270-mesh sieves. Release rate and direct total determinations indicated that some measure of timed release appeared in all four sieve samples. The pH-release rate profiles of the microcapsules indicated that dissoution was pH independent. Colloidal silica and isopropyl myristate formulations provided the best suspending characteristics of all aerosol formulations evaluated. Delivery rate, pressure, and evacuation testing demonstrated the usability and functionality of the aerosol. An evaluation was made on the effect on urinary excretion levels of 17-hydroxycorticosteroid when a physical admixture of the drug and timed-release microcapsules were sprayed on rabbits. The significantly higher 17-hydroxycorticosteroid levels obtained in urine of animals treated with the admixture after 1 day may have been attributed to both an immediate suppression of the endogenous steroid and the \"spilling over\" of excess dexamethasone. A significant difference also was found at the 90% confidence level among the 24, 48, and 72-hr 17-hydroxycorticosteroid levels in the admixture and the microcapsules, which substantiated the delayed effect of the latter.", "contents": "Development and evaluation of a dexamethasone timed-release aerosol formulation. Dexamethasone microcapcules were prepared and in vitro parameters were determined by sieve analysis which yielded materials retained on Nos. 80-, 100-, 200-, and 270-mesh sieves. Release rate and direct total determinations indicated that some measure of timed release appeared in all four sieve samples. The pH-release rate profiles of the microcapsules indicated that dissoution was pH independent. Colloidal silica and isopropyl myristate formulations provided the best suspending characteristics of all aerosol formulations evaluated. Delivery rate, pressure, and evacuation testing demonstrated the usability and functionality of the aerosol. An evaluation was made on the effect on urinary excretion levels of 17-hydroxycorticosteroid when a physical admixture of the drug and timed-release microcapsules were sprayed on rabbits. The significantly higher 17-hydroxycorticosteroid levels obtained in urine of animals treated with the admixture after 1 day may have been attributed to both an immediate suppression of the endogenous steroid and the \"spilling over\" of excess dexamethasone. A significant difference also was found at the 90% confidence level among the 24, 48, and 72-hr 17-hydroxycorticosteroid levels in the admixture and the microcapsules, which substantiated the delayed effect of the latter."}
{"id": "PMID:239189", "title": "Effect of flavoring oils on preservative concentrations in oral liquid dosage forms.", "content": "The partitioning of methyl-, ethyl-, propyl-, and butylparabens into flavoring oils from aqueous systems was studied. The partitioning is dependent on the concentration of the flavoring oil, the pH of the aqueous medium, and the nature and concentration of additives to the aqueous medium.", "contents": "Effect of flavoring oils on preservative concentrations in oral liquid dosage forms. The partitioning of methyl-, ethyl-, propyl-, and butylparabens into flavoring oils from aqueous systems was studied. The partitioning is dependent on the concentration of the flavoring oil, the pH of the aqueous medium, and the nature and concentration of additives to the aqueous medium."}
{"id": "PMID:239190", "title": "Transformation of 2,2'-anhydro-1-beta-D-arabinofuranosylcytosine induced by hydrogen peroxide.", "content": "2,2'-Anhydro-1-beta-D-arabinofuranosylcytosine (I) is a more potent and less toxic antineoplastic agent than is cytarabine (1-beta-D-arabinofuranosylcytosine) (II). The anhydronucleoside (I) was found to be readily transformed by hydrogen peroxide into 2,2'-anhydro-5-hydroxy-1-beta-D-arabinofuranosylcytosine (III) by treatment with 0.025 M hydrogen peroxide at a neutral and slightly basic pH range (pH 6-9) and at room temperature. It was converted into non-UV-absorbing substance(s) by hydrogen peroxide at an alkaline pH (pH 11). Since hydrogen peroxide is produced by redox reactions in all living cells, it may be responsible for the alteration of I. Such transformations by hydrogen peroxide were not observed with cytarabine.", "contents": "Transformation of 2,2'-anhydro-1-beta-D-arabinofuranosylcytosine induced by hydrogen peroxide. 2,2'-Anhydro-1-beta-D-arabinofuranosylcytosine (I) is a more potent and less toxic antineoplastic agent than is cytarabine (1-beta-D-arabinofuranosylcytosine) (II). The anhydronucleoside (I) was found to be readily transformed by hydrogen peroxide into 2,2'-anhydro-5-hydroxy-1-beta-D-arabinofuranosylcytosine (III) by treatment with 0.025 M hydrogen peroxide at a neutral and slightly basic pH range (pH 6-9) and at room temperature. It was converted into non-UV-absorbing substance(s) by hydrogen peroxide at an alkaline pH (pH 11). Since hydrogen peroxide is produced by redox reactions in all living cells, it may be responsible for the alteration of I. Such transformations by hydrogen peroxide were not observed with cytarabine."}
{"id": "PMID:239191", "title": "Drug-biomolecule interactions: interactions of mononucleotides and polybasic amino acids.", "content": "Histones and ribosomal proteins are basic proteins that participate in gene regulation and protein synthesis, respectively. How these proteins interact with nucleic acids is not yet clear, although specificities in these interactions have been observed. Study of the interaction of mononucleotides with basic polyamino acids is one approach to understanding such interactions. The results of studies with the mononucleotides can help elucidate the normal molecular processes in biological systems and also shed light on some effects of drugs, such as puromycin and tubericidin, that are nucleotide derivatives. A review of studies on the interaction of mononucleotides and basic polyamino acids such as polylysine and polyarginine is presented. In addition, a short review of the self-associative properties of mononucleotides is given. Studies of the mononucleotide-polyamino acid interaction have involved a wide variety of techniques including equilibrium dialysis, NMR, optical rotatory dispersion, circular dichroism, and precipitate analysis.", "contents": "Drug-biomolecule interactions: interactions of mononucleotides and polybasic amino acids. Histones and ribosomal proteins are basic proteins that participate in gene regulation and protein synthesis, respectively. How these proteins interact with nucleic acids is not yet clear, although specificities in these interactions have been observed. Study of the interaction of mononucleotides with basic polyamino acids is one approach to understanding such interactions. The results of studies with the mononucleotides can help elucidate the normal molecular processes in biological systems and also shed light on some effects of drugs, such as puromycin and tubericidin, that are nucleotide derivatives. A review of studies on the interaction of mononucleotides and basic polyamino acids such as polylysine and polyarginine is presented. In addition, a short review of the self-associative properties of mononucleotides is given. Studies of the mononucleotide-polyamino acid interaction have involved a wide variety of techniques including equilibrium dialysis, NMR, optical rotatory dispersion, circular dichroism, and precipitate analysis."}
{"id": "PMID:239192", "title": "Drug-biomolecule interactions: mechanism of ligand interactions with carbonic anhydrase studied by magnetic resonance relaxation and rapid reaction methods.", "content": "Kinetcs of interaction between the metalloenzyme carbonic anhydrase and either monovalent anions or aromatic sulfonamides were examined by three distinct fast reaction techniques: stopped flow, equilibrium perturbation, and magentic resonance relaxation. By correlating spectroscopic data on conformational and ionization equilibria of the complex and free species with the reaction kinetics, a relatively complete description of the mechanism can be presented. A proton-dependent equilibrium between two coordination forms of the free enzyme can be demonstrated spectroscopically. Anions selectively combine with the form predominating at low pH. For a series of carboxylate ligands, formate and substituted acetates, anion association is found to be three orders of magnitude greater than similar ligand substitution processes known in inorganic chemistry. For sulfonamide association, the attacking species are the form of carbonic anhydrase predominating at high pH and the neutral sulfonamide. Combination involving the neutral species is followed by loss of a proton to form the sulfonamido anion in the stabilized complex. This obligate proton transfer offers a probable explanation for the unique specificity of sulfonamides in inhibiting this enzyme. The anionic sulfonamido moiety can be shown to resemble closely a transition intermediate in the catalytic step of substrate hydration.", "contents": "Drug-biomolecule interactions: mechanism of ligand interactions with carbonic anhydrase studied by magnetic resonance relaxation and rapid reaction methods. Kinetcs of interaction between the metalloenzyme carbonic anhydrase and either monovalent anions or aromatic sulfonamides were examined by three distinct fast reaction techniques: stopped flow, equilibrium perturbation, and magentic resonance relaxation. By correlating spectroscopic data on conformational and ionization equilibria of the complex and free species with the reaction kinetics, a relatively complete description of the mechanism can be presented. A proton-dependent equilibrium between two coordination forms of the free enzyme can be demonstrated spectroscopically. Anions selectively combine with the form predominating at low pH. For a series of carboxylate ligands, formate and substituted acetates, anion association is found to be three orders of magnitude greater than similar ligand substitution processes known in inorganic chemistry. For sulfonamide association, the attacking species are the form of carbonic anhydrase predominating at high pH and the neutral sulfonamide. Combination involving the neutral species is followed by loss of a proton to form the sulfonamido anion in the stabilized complex. This obligate proton transfer offers a probable explanation for the unique specificity of sulfonamides in inhibiting this enzyme. The anionic sulfonamido moiety can be shown to resemble closely a transition intermediate in the catalytic step of substrate hydration."}
{"id": "PMID:239193", "title": "Drug-biomolecule interactions: proton magnetic resonance studies of complex formation between bovine neurophysins and oxytocin at molecular level.", "content": "Proton magnetic resonance spectroscopy was used to monitor individual amino acid residues in bovine neurophysin, in the nonapeptide hormone oxytocin, and in the complex formed between them. For neurophysin I alone, a normal titration curve for the C-2 proton resonance of the lone histidine residue was obtained with an apparent ionization constant of 6.9 addition of oxytocin to a solution of neurophysin I at pH 6.5 resulted in several changes in the spectrum. The effect on the histidine C-2 proton resonance signal indicated a slow exchange process between two states, probably representing a conformational change in the protein. The apparent pK of the histidine residue in the hormonal complex was shifted to 6.7, indicating a slightly more positive (less electron dense) environment for the histidine residue. Resonances of the single tyrosine residue of oxytocin were observed to broaden significantly, but not to shift appreciably, on the addition of neurophysin II. These observations may indicate involvement of the tyrosyl residue of oxytocin in the hormone-\"carrier protein\" interaction.", "contents": "Drug-biomolecule interactions: proton magnetic resonance studies of complex formation between bovine neurophysins and oxytocin at molecular level. Proton magnetic resonance spectroscopy was used to monitor individual amino acid residues in bovine neurophysin, in the nonapeptide hormone oxytocin, and in the complex formed between them. For neurophysin I alone, a normal titration curve for the C-2 proton resonance of the lone histidine residue was obtained with an apparent ionization constant of 6.9 addition of oxytocin to a solution of neurophysin I at pH 6.5 resulted in several changes in the spectrum. The effect on the histidine C-2 proton resonance signal indicated a slow exchange process between two states, probably representing a conformational change in the protein. The apparent pK of the histidine residue in the hormonal complex was shifted to 6.7, indicating a slightly more positive (less electron dense) environment for the histidine residue. Resonances of the single tyrosine residue of oxytocin were observed to broaden significantly, but not to shift appreciably, on the addition of neurophysin II. These observations may indicate involvement of the tyrosyl residue of oxytocin in the hormone-\"carrier protein\" interaction."}
{"id": "PMID:239194", "title": "Drug-biomolecule interactions: interaction of gentamicin with lipid monomolecular films.", "content": "The interaction of gentamicin with monomolecular films of a series of biologically important lipids spread on an aqueous buffered subphase was studied. The surface pressure, pi, of these films was determined by the Wilhelmy plate method as a function of surface area, A, and pi-A curves were constructed. Changes in the pi-A characteristics in the presence of gentamicin were used as a measure of antibiotic-film interaction. No interaction was observed between gentamicin and films of cholesterol, egg lecithin, dipalmitoyl lecithin, phosphatidyl ethanolamine, stearyl alcohol, and bovine ceramides at all pH values studied. Stearic acid films showed no interaction with gentamicin at pH 5. At pH 7 and 8, a small increase in pressure (approximately 3 dynes/cm) was noted. A dramatic increase in surface pressure was observed in the presence of stearyl aldehyde films ranging from approximately 9 dynes/cm at pH 7,2 to 23 dynes/cm at pH 8.4. This effect was attributed to a Schiff-base reaction between the nonprotonated primary amino groups on the gentamicin molecule and the stearyl aldehyde. Further evidence was reported by the fact that the addition of glucose (which has been reported to participate in Schiff-base formation with amines) to the subphase inhibited the stearyl aldehyde-gentamicin interaction. Sucrose did not show a corresponding effect. The addition of sodium bisulfite, which reacts with aldehydes to form alpha-hydroxysulfonic acid, also inhibited the gentamicin-stearyl aldehyde interaction. It is postulated that Schiff-base formation is a step in the in vivo transport of gentamicin across the membrane of sensitive organisms.", "contents": "Drug-biomolecule interactions: interaction of gentamicin with lipid monomolecular films. The interaction of gentamicin with monomolecular films of a series of biologically important lipids spread on an aqueous buffered subphase was studied. The surface pressure, pi, of these films was determined by the Wilhelmy plate method as a function of surface area, A, and pi-A curves were constructed. Changes in the pi-A characteristics in the presence of gentamicin were used as a measure of antibiotic-film interaction. No interaction was observed between gentamicin and films of cholesterol, egg lecithin, dipalmitoyl lecithin, phosphatidyl ethanolamine, stearyl alcohol, and bovine ceramides at all pH values studied. Stearic acid films showed no interaction with gentamicin at pH 5. At pH 7 and 8, a small increase in pressure (approximately 3 dynes/cm) was noted. A dramatic increase in surface pressure was observed in the presence of stearyl aldehyde films ranging from approximately 9 dynes/cm at pH 7,2 to 23 dynes/cm at pH 8.4. This effect was attributed to a Schiff-base reaction between the nonprotonated primary amino groups on the gentamicin molecule and the stearyl aldehyde. Further evidence was reported by the fact that the addition of glucose (which has been reported to participate in Schiff-base formation with amines) to the subphase inhibited the stearyl aldehyde-gentamicin interaction. Sucrose did not show a corresponding effect. The addition of sodium bisulfite, which reacts with aldehydes to form alpha-hydroxysulfonic acid, also inhibited the gentamicin-stearyl aldehyde interaction. It is postulated that Schiff-base formation is a step in the in vivo transport of gentamicin across the membrane of sensitive organisms."}
{"id": "PMID:239195", "title": "Drug-biomolecule interactions: bioelectrometric study of the mechanism of carbachol interactions with the cornea and its relation to miotic activity.", "content": "The augmentation of carbachol miotic activity attributable to enhanced transcorneal absorption, which results from the action of cationic adjuvants included in ophthalmic vehicles, suggested a study of carbachol-corneal tissue interaction as a further step toward understanding the phenomenon. The present study was performed in vivo using an innocuous electrometric technique. A fixed charge density of the corneal epithelial surface versus carbachol concentration profile was obtained from the electrometric results; it revealed three distinct concentration regions defined by precipitous decreases of fixed charge over extremely small concentration ranges. This anomalous behavior is attributed to cooperative alterations in the binding affinities of fixed anionic sites on the tissue surface, which result in an all-or-none release of protons and/or other nicrocations. The unmasked anionic sites become reoccupied with carbachol except in the last region where the reoccupation by carbachol is competitive with other cations in the solution in contact with the surface. This behavior, postulated on the basis of the construction of a carbachol-tissue binding isotherm from which thermodynamic interaction affinities were computed, was corroborated by the observed dependency of the duration of miotic activity on carbachol concentration. Allosteric interactions between anionic binding sites, which are mediated through electron inductive and electrostatic field effects and likely involve a cooperative alteration in tissue water structure, are implicated as underlying the observed phenomena.", "contents": "Drug-biomolecule interactions: bioelectrometric study of the mechanism of carbachol interactions with the cornea and its relation to miotic activity. The augmentation of carbachol miotic activity attributable to enhanced transcorneal absorption, which results from the action of cationic adjuvants included in ophthalmic vehicles, suggested a study of carbachol-corneal tissue interaction as a further step toward understanding the phenomenon. The present study was performed in vivo using an innocuous electrometric technique. A fixed charge density of the corneal epithelial surface versus carbachol concentration profile was obtained from the electrometric results; it revealed three distinct concentration regions defined by precipitous decreases of fixed charge over extremely small concentration ranges. This anomalous behavior is attributed to cooperative alterations in the binding affinities of fixed anionic sites on the tissue surface, which result in an all-or-none release of protons and/or other nicrocations. The unmasked anionic sites become reoccupied with carbachol except in the last region where the reoccupation by carbachol is competitive with other cations in the solution in contact with the surface. This behavior, postulated on the basis of the construction of a carbachol-tissue binding isotherm from which thermodynamic interaction affinities were computed, was corroborated by the observed dependency of the duration of miotic activity on carbachol concentration. Allosteric interactions between anionic binding sites, which are mediated through electron inductive and electrostatic field effects and likely involve a cooperative alteration in tissue water structure, are implicated as underlying the observed phenomena."}
{"id": "PMID:239196", "title": "Drug-biomolecule interactions: drug toxicity and vitamin coenzyme depletion.", "content": "Thirteen pyridine compounds, phenylbutazone, and three salicylates were studied for their effects upon the turnover of 7-14C-nicotinamide dinucleotides in the mouse. The compounds were administered at equitoxic doses (LD25) to 7-14C-nicotinic acid- (niacin) pretreated mice, and the induced excretion of urinary-14C was analyzed in terms of total 14C and percentage of total 14C as known metabolites of nicotinic acid. Of the 17 compounds, 12 afforded significant alterations in the total 14C excreted and five of these caused alterations in the disposition of the 7-14C-nicotinamide endogenously liberated from the 7-14C-nicotinamide adenine dinucleotide pool. Comparative depletions of 14C from brain, lungs, liver, and kidneys were studied with 10 of the pyridine compounds. Several tissues were found to be the sources of the urinary-14C, with the lungs being the most accessible source. Some compounds had effects at doses less than the LD25's, as shown by increased hexobarbital sleeping time in acute experiments with rats. These pyridine compounds were initially considered to act at the level of the nicotinamide dinucleotides in the normal biosynthetic pathway (nicotinic acid site) and/or at the level of glycohydrolase (nicotinamide site). In view of the inclusion of nicotinic acid, nicotinamide, salicylic acid, and phenylbutazone in this correlation between toxicity and 7-14C-nicotinamide mobilization, it is not necessary that the formation of compounds analogous to the nicotinamide dinucleotides plays a significant role in the toxic manifestations of the nicotinamide analogs. The displacement of 7-14C-nicotinamide dinucleotides from their corresponding apoenzymes with subsequent metabolism of the dinucleotides could explain the noted increased 7-14C-nicotinamide dinucleotide turnover and depletion which led to the toxic effects.", "contents": "Drug-biomolecule interactions: drug toxicity and vitamin coenzyme depletion. Thirteen pyridine compounds, phenylbutazone, and three salicylates were studied for their effects upon the turnover of 7-14C-nicotinamide dinucleotides in the mouse. The compounds were administered at equitoxic doses (LD25) to 7-14C-nicotinic acid- (niacin) pretreated mice, and the induced excretion of urinary-14C was analyzed in terms of total 14C and percentage of total 14C as known metabolites of nicotinic acid. Of the 17 compounds, 12 afforded significant alterations in the total 14C excreted and five of these caused alterations in the disposition of the 7-14C-nicotinamide endogenously liberated from the 7-14C-nicotinamide adenine dinucleotide pool. Comparative depletions of 14C from brain, lungs, liver, and kidneys were studied with 10 of the pyridine compounds. Several tissues were found to be the sources of the urinary-14C, with the lungs being the most accessible source. Some compounds had effects at doses less than the LD25's, as shown by increased hexobarbital sleeping time in acute experiments with rats. These pyridine compounds were initially considered to act at the level of the nicotinamide dinucleotides in the normal biosynthetic pathway (nicotinic acid site) and/or at the level of glycohydrolase (nicotinamide site). In view of the inclusion of nicotinic acid, nicotinamide, salicylic acid, and phenylbutazone in this correlation between toxicity and 7-14C-nicotinamide mobilization, it is not necessary that the formation of compounds analogous to the nicotinamide dinucleotides plays a significant role in the toxic manifestations of the nicotinamide analogs. The displacement of 7-14C-nicotinamide dinucleotides from their corresponding apoenzymes with subsequent metabolism of the dinucleotides could explain the noted increased 7-14C-nicotinamide dinucleotide turnover and depletion which led to the toxic effects."}
{"id": "PMID:239197", "title": "Lidocaine hydrochloride absorption from a subcutaneous site.", "content": "Subcutaneous disappearance of lidocaine hydrochloride was followed as a function of time using a specially designed \"closed\" subcutaneous absorption cell affixed to anesthetized rats. Unbuffered, stirred lidocaine hydrochloride solutions in cells open to the atmosphere were previously shown to increase in pH with time because of carbon dioxide loss. The closed cell was designed to prevent this loss, but pH shifts still occurred, making the derivation of a simple pharmacokinetic absorption model impossible. Because the pH of the solution shifted to higher pH values, the data suggest that precipitation of lidocaine base may have occurred in some experiments.", "contents": "Lidocaine hydrochloride absorption from a subcutaneous site. Subcutaneous disappearance of lidocaine hydrochloride was followed as a function of time using a specially designed \"closed\" subcutaneous absorption cell affixed to anesthetized rats. Unbuffered, stirred lidocaine hydrochloride solutions in cells open to the atmosphere were previously shown to increase in pH with time because of carbon dioxide loss. The closed cell was designed to prevent this loss, but pH shifts still occurred, making the derivation of a simple pharmacokinetic absorption model impossible. Because the pH of the solution shifted to higher pH values, the data suggest that precipitation of lidocaine base may have occurred in some experiments."}
{"id": "PMID:239198", "title": "Fluorometric assay of bethanidine in plasma.", "content": "A fluorometric method for determining bethanidine in blood plasma is described. The bethanidine is extracted into chloroform, a drug-dye complex with eosin Y is formed, and the fluorescence is measured (excitation, 535 nm; fluorescence, 560 nm). The assay detects 0.02 muM bethanidine (4 ng/ml) in plasma. The relative fluorescence of several body constituents and antihypertensive drugs is negligible. The plasma levels of bethanidine in four hypertensive patients receiving this drug were measured.", "contents": "Fluorometric assay of bethanidine in plasma. A fluorometric method for determining bethanidine in blood plasma is described. The bethanidine is extracted into chloroform, a drug-dye complex with eosin Y is formed, and the fluorescence is measured (excitation, 535 nm; fluorescence, 560 nm). The assay detects 0.02 muM bethanidine (4 ng/ml) in plasma. The relative fluorescence of several body constituents and antihypertensive drugs is negligible. The plasma levels of bethanidine in four hypertensive patients receiving this drug were measured."}
{"id": "PMID:239199", "title": "Automated system for analytical microbiology V: calibration lines for antibiotics.", "content": "The accuracy of an automated system for the microbiological assay of antibiotics was increased by improvement attendant to connection to an on-line computer. The system was used to investigate the suitability of four forms of interpolation formulas by assaying for chlortetracycline and erythromycin. The calibration lines were prepared as point-to-point straight-line approximations and as cubic equations. Cubic equations through four calibration points were preferred. Since the automated system was a four-channel instrument, a separate response line was prepared for each channel. Combining the four response lines into one could substantially degrade the accuracy and precision of assays. A new general equation relating the response of the test organism to concentrations of active materials was used to account for factors in addition to the antibiotic upon the dose-response line. Some of these factors were: diluents, growth substances, relative proportions of mixed antibiotics, pH and buffer capacities of the sample solution and assay broth, salts, and organic compounds in samples and not in standard solutions. The equation was used to show under what conditions the dose-response lines of mixtures and single-component antibiotics could be the same. It could also account for the nonspecific nature of turbidimetric assays. The equation showed assay biases to be caused not by differences in composition of antibiotics in standards and samples but by differences in other substances affecting growth of the test organism. A new dose-response line applicable to assays using Klebsiella pneumoniae was described.", "contents": "Automated system for analytical microbiology V: calibration lines for antibiotics. The accuracy of an automated system for the microbiological assay of antibiotics was increased by improvement attendant to connection to an on-line computer. The system was used to investigate the suitability of four forms of interpolation formulas by assaying for chlortetracycline and erythromycin. The calibration lines were prepared as point-to-point straight-line approximations and as cubic equations. Cubic equations through four calibration points were preferred. Since the automated system was a four-channel instrument, a separate response line was prepared for each channel. Combining the four response lines into one could substantially degrade the accuracy and precision of assays. A new general equation relating the response of the test organism to concentrations of active materials was used to account for factors in addition to the antibiotic upon the dose-response line. Some of these factors were: diluents, growth substances, relative proportions of mixed antibiotics, pH and buffer capacities of the sample solution and assay broth, salts, and organic compounds in samples and not in standard solutions. The equation was used to show under what conditions the dose-response lines of mixtures and single-component antibiotics could be the same. It could also account for the nonspecific nature of turbidimetric assays. The equation showed assay biases to be caused not by differences in composition of antibiotics in standards and samples but by differences in other substances affecting growth of the test organism. A new dose-response line applicable to assays using Klebsiella pneumoniae was described."}
{"id": "PMID:239200", "title": "Ultracentrifugal study of effect of sodium chloride on micelle size of fusidate sodium.", "content": "Apparent micellar molecular weights were determined with the antibiotic fusidate sodium by ultracentrifugation in varying counterion concentrations (Na+). The effects of buffer salts, pH, sodium chloride concentration, and drug concentration were studied. The results strongly support the concept of the formation of primary micelles composed of five monomer units, followed by aggregation of the pentomers into larger micelles as salt concentration increases.", "contents": "Ultracentrifugal study of effect of sodium chloride on micelle size of fusidate sodium. Apparent micellar molecular weights were determined with the antibiotic fusidate sodium by ultracentrifugation in varying counterion concentrations (Na+). The effects of buffer salts, pH, sodium chloride concentration, and drug concentration were studied. The results strongly support the concept of the formation of primary micelles composed of five monomer units, followed by aggregation of the pentomers into larger micelles as salt concentration increases."}
{"id": "PMID:239201", "title": "Synthesis of potential adrenergic blocking agents: 2-substituted aminomethylnaphthol(2,3-b)-1,4-dioxans.", "content": "Eleven 2-substituted aminomethylnaphtho(2,3-b)-1,4-dioxans were synthesized. The nucleophilic displacement of 2-tosyloxymethylnaphtho(2,3-b)-1,4-dioxan by appropriate amines was carried out using dimethyl sulfoxide as the solvent. Preliminary pharmacological evaluation revealed a potentiation of norepinephrine at low doses and a noncompetitive antagonism at high doses in the rat vas deferens and a dose-related hypotensive action of short duration in the anesthetized rat.", "contents": "Synthesis of potential adrenergic blocking agents: 2-substituted aminomethylnaphthol(2,3-b)-1,4-dioxans. Eleven 2-substituted aminomethylnaphtho(2,3-b)-1,4-dioxans were synthesized. The nucleophilic displacement of 2-tosyloxymethylnaphtho(2,3-b)-1,4-dioxan by appropriate amines was carried out using dimethyl sulfoxide as the solvent. Preliminary pharmacological evaluation revealed a potentiation of norepinephrine at low doses and a noncompetitive antagonism at high doses in the rat vas deferens and a dose-related hypotensive action of short duration in the anesthetized rat."}
{"id": "PMID:239203", "title": "Liquid chromatography in pharmaceutical analysis III: separation of diuretic-antihypertensive mixtures.", "content": "High-pressure liquid chromatography was used to optimize the resolution of therapeutic agents commonly found in antihypertensive preparations. Seven widely prescribed drugs were investigated. The compounds were chromatographed on reversed-phase octadecyltrichlorosilane (C18) or diphenyldichlorosilane (phenyl) columns, using mixtures of acetonitrile or absolute methanol and distilled water buffered with ammonium acetate, ammonium chloride, or ammonium carbonate. By calculating approximate resolution values, the separation of selected drug mixtures can be predicted.", "contents": "Liquid chromatography in pharmaceutical analysis III: separation of diuretic-antihypertensive mixtures. High-pressure liquid chromatography was used to optimize the resolution of therapeutic agents commonly found in antihypertensive preparations. Seven widely prescribed drugs were investigated. The compounds were chromatographed on reversed-phase octadecyltrichlorosilane (C18) or diphenyldichlorosilane (phenyl) columns, using mixtures of acetonitrile or absolute methanol and distilled water buffered with ammonium acetate, ammonium chloride, or ammonium carbonate. By calculating approximate resolution values, the separation of selected drug mixtures can be predicted."}
{"id": "PMID:239204", "title": "Rapid fluorometric determination of procainamide hydrochloride dosage forms.", "content": "A fluorometric procedure for procainamide hydrochloride was developed, and it offers improvements in ease, speed, and sensitivity over the official method. The new procedure is based on the reaction with fluorescamine in aqueous medium at pH 7.5 to form a fluorophore, with activation and emission wavelengths of 400 and 485 nm, respectively. The fluorescence is linear (r = 0.999) over the 0. 04-1 mug/ml concentration range and is stable for at least 2 hr. Recovery data appeared to be accurate, quantitative, and reproducible. The overall recovery was 99.8% with a standard deviation of +/-1.14 (n = 5). The method was successfully applied to commercially available dosage forms.", "contents": "Rapid fluorometric determination of procainamide hydrochloride dosage forms. A fluorometric procedure for procainamide hydrochloride was developed, and it offers improvements in ease, speed, and sensitivity over the official method. The new procedure is based on the reaction with fluorescamine in aqueous medium at pH 7.5 to form a fluorophore, with activation and emission wavelengths of 400 and 485 nm, respectively. The fluorescence is linear (r = 0.999) over the 0. 04-1 mug/ml concentration range and is stable for at least 2 hr. Recovery data appeared to be accurate, quantitative, and reproducible. The overall recovery was 99.8% with a standard deviation of +/-1.14 (n = 5). The method was successfully applied to commercially available dosage forms."}
{"id": "PMID:239205", "title": "Synthesis and pharmacological activity of 5-substituted 2-(N,N-dialkylaminoethyl)amino- and 2-N-methylpiperazinyl-1,3,4-thiadiazoles.", "content": "5-Substituted 2-amino-1,3,4-thiadiazoles were transformed to their corresponding 2-bromo derivatives. The reaction of the 5-substituted 2-bromo-1,3,4-thiadiazoles with N,N-dialkylaminoethylamines or N-methylpiperazine afforded the corresponding amino-1,3,4-thiadiazole derivatives. All prepared compounds displayed antihistaminic, anticholinergic, and norepinephrine-potentiating activities.", "contents": "Synthesis and pharmacological activity of 5-substituted 2-(N,N-dialkylaminoethyl)amino- and 2-N-methylpiperazinyl-1,3,4-thiadiazoles. 5-Substituted 2-amino-1,3,4-thiadiazoles were transformed to their corresponding 2-bromo derivatives. The reaction of the 5-substituted 2-bromo-1,3,4-thiadiazoles with N,N-dialkylaminoethylamines or N-methylpiperazine afforded the corresponding amino-1,3,4-thiadiazole derivatives. All prepared compounds displayed antihistaminic, anticholinergic, and norepinephrine-potentiating activities."}
{"id": "PMID:239206", "title": "Interaction of substituted benzoic acids with polysorbate 20 micelles.", "content": "Equilibrium solubilities of a series of substituted benzoic acids in different concentrations of polysorbate 20 at controlled pH were measured. The maintenance of pH was achieved using a pH-stat assembly. A linear relationship was found between the amount of benzoic acid solubilized and surfactant concentration. As solubilizate polarity increased, the amount solubilized also increased. Solubility data were analyzed, and the interaction between solubilizate molecules and micelles was calculated in terms of partition coefficients of ionized and unionized molecules between aqueous and micellar phases. A linear relationship between pi values (log partition coefficients) of functional groups and aqueous-micellar partition coefficient was found.", "contents": "Interaction of substituted benzoic acids with polysorbate 20 micelles. Equilibrium solubilities of a series of substituted benzoic acids in different concentrations of polysorbate 20 at controlled pH were measured. The maintenance of pH was achieved using a pH-stat assembly. A linear relationship was found between the amount of benzoic acid solubilized and surfactant concentration. As solubilizate polarity increased, the amount solubilized also increased. Solubility data were analyzed, and the interaction between solubilizate molecules and micelles was calculated in terms of partition coefficients of ionized and unionized molecules between aqueous and micellar phases. A linear relationship between pi values (log partition coefficients) of functional groups and aqueous-micellar partition coefficient was found."}
{"id": "PMID:239207", "title": "Confirmation of iminoacridan structure of singly protonated 9-aminoacridine.", "content": "The occurrence of the second absorption band of singly protonated 9-aminoacridine, which arises from an acridinium ring-localized transition, at anomalously short wavelength indicates the disruption of the aromaticity of the central ring of the singly charged cation. The shifting of the two longest wavelength absorption bands and the fluorescence band of 10-methyl-9-aminoacridine monocation, a model of singly protonated 9-aminoacridine which is constrained to dissociate from the exocyclic nitrogen atom, to shorter wavelengths, upon dissociation, indicates the imine-like nature of the 10-methyl derivative. Thes observations support the conclusion that the predominant site of positive charge in singly protonated 9-aminoacridine is the exocyclic nitrogen atom, even though the heterocyclic nitrogen atom is the site of protonation of the neutral molecule.", "contents": "Confirmation of iminoacridan structure of singly protonated 9-aminoacridine. The occurrence of the second absorption band of singly protonated 9-aminoacridine, which arises from an acridinium ring-localized transition, at anomalously short wavelength indicates the disruption of the aromaticity of the central ring of the singly charged cation. The shifting of the two longest wavelength absorption bands and the fluorescence band of 10-methyl-9-aminoacridine monocation, a model of singly protonated 9-aminoacridine which is constrained to dissociate from the exocyclic nitrogen atom, to shorter wavelengths, upon dissociation, indicates the imine-like nature of the 10-methyl derivative. Thes observations support the conclusion that the predominant site of positive charge in singly protonated 9-aminoacridine is the exocyclic nitrogen atom, even though the heterocyclic nitrogen atom is the site of protonation of the neutral molecule."}
{"id": "PMID:239208", "title": "High-pressure liquid chromatographic analysis of triflubazam and its metabolites in human and animal blood and urine.", "content": "A high-pressure liquid chromatographic method is described for analyzing triflubazam [1-methyl-5-phenyl-7-trifluoromethyl-1H-1,5-benzodiazepine-2,4(3H,5H)-dione] and its primary metabolites in blood and urine. Adsorption chromatography, using pellicular silica gel as the stationary phase and dioxane-isooctane as the mobile phase, permitted rapid sample analysis. After extraction of blood and urine samples with toluene, quantitation is achieved using liquid chromatography with an internal standard. The method is sensitive above 50 ng/ml of triflubazam and its known metabolites. Recoveries for all compounds from blood or urine averaged above 95 percent. The specificity of the method was established by collecting samples separated by liquid chromatography and characterizing them by mass spectrometry. Human and animal data are presented to illustrate the utility of the method.", "contents": "High-pressure liquid chromatographic analysis of triflubazam and its metabolites in human and animal blood and urine. A high-pressure liquid chromatographic method is described for analyzing triflubazam [1-methyl-5-phenyl-7-trifluoromethyl-1H-1,5-benzodiazepine-2,4(3H,5H)-dione] and its primary metabolites in blood and urine. Adsorption chromatography, using pellicular silica gel as the stationary phase and dioxane-isooctane as the mobile phase, permitted rapid sample analysis. After extraction of blood and urine samples with toluene, quantitation is achieved using liquid chromatography with an internal standard. The method is sensitive above 50 ng/ml of triflubazam and its known metabolites. Recoveries for all compounds from blood or urine averaged above 95 percent. The specificity of the method was established by collecting samples separated by liquid chromatography and characterizing them by mass spectrometry. Human and animal data are presented to illustrate the utility of the method."}
{"id": "PMID:239209", "title": "Effect of self-association on rate of penicillin G degradation in concentrated aqueous solutions.", "content": "The apparent rate of degradation of penicillin G potassium micellar solutions of 500,000 units/ml, a concentration commonly encountered in vials reconstituted for storage in the refrigerator, was investigated and compared to that of nonmicellar solutions of 8000 units/ml at 25 degrees, ionic strength of 1.1 M, and pH range from 5.0 to 9.5. In the micellar solutions the apparent rate of the H+-catalyzed degradation was increased twofold but that of water- and OH minus-catalyzed hydrolysis was decreased two- to three-fold. Consequently, the pH-rate profile of the micellar solutions was shifted to higher pH values and the pH of minimum degradation was found to be at 7.0 compared to 6.5 for the nonmicellar solution of the same ionic strength. Compared at their respective pH-rate profile minima, micellar penicillin G is 2.5 times as stable as the nonmicellar solution under the conditions of constant pH and ionic strength.", "contents": "Effect of self-association on rate of penicillin G degradation in concentrated aqueous solutions. The apparent rate of degradation of penicillin G potassium micellar solutions of 500,000 units/ml, a concentration commonly encountered in vials reconstituted for storage in the refrigerator, was investigated and compared to that of nonmicellar solutions of 8000 units/ml at 25 degrees, ionic strength of 1.1 M, and pH range from 5.0 to 9.5. In the micellar solutions the apparent rate of the H+-catalyzed degradation was increased twofold but that of water- and OH minus-catalyzed hydrolysis was decreased two- to three-fold. Consequently, the pH-rate profile of the micellar solutions was shifted to higher pH values and the pH of minimum degradation was found to be at 7.0 compared to 6.5 for the nonmicellar solution of the same ionic strength. Compared at their respective pH-rate profile minima, micellar penicillin G is 2.5 times as stable as the nonmicellar solution under the conditions of constant pH and ionic strength."}
{"id": "PMID:239210", "title": "Nonisothermal kinetic studies III: rapid nonisothermal-isothermal method for stability prediction.", "content": "A continuous nonisothermal-isothermal method for stability prediction was developed. The approach yields all necessary parameters for prediction, including reaction order. The experimental procedure involves changing the temperature of the samples being studied until degradation is rapid enough to proceed at a convenient isothermal rate for a sufficient number of half-lives with adequate analytical sensitivity so that the reaction order can be unambiguously determined. The analytical information obtained during the nonisothermal and isothermal portions of the experiment is utilized without curve matching in calculating the activation energy and determining the reaction order, reaction rate, and stability prediction at any desired temperature. Model experiments include the acid-catalyzed hydrolysis of acetylcholine bromide and the inversion of sucrose.", "contents": "Nonisothermal kinetic studies III: rapid nonisothermal-isothermal method for stability prediction. A continuous nonisothermal-isothermal method for stability prediction was developed. The approach yields all necessary parameters for prediction, including reaction order. The experimental procedure involves changing the temperature of the samples being studied until degradation is rapid enough to proceed at a convenient isothermal rate for a sufficient number of half-lives with adequate analytical sensitivity so that the reaction order can be unambiguously determined. The analytical information obtained during the nonisothermal and isothermal portions of the experiment is utilized without curve matching in calculating the activation energy and determining the reaction order, reaction rate, and stability prediction at any desired temperature. Model experiments include the acid-catalyzed hydrolysis of acetylcholine bromide and the inversion of sucrose."}
{"id": "PMID:239211", "title": "Liquid chromatography in pharmaceutical analysis IV: determination of antispasmodic mixtures.", "content": "Parameters associated with the separation of antianxiety-antispasmodic agents were investigated using high-pressure liquid chromatography. Eight widely prescribed drugs were studied. The compounds were chromatographed on reversed-phase octadecyltrichlorosilane (C18) or diphenyldichlorosilane (phenyl) columns, using mixtures of absolute methanol and distilled water buffered with ammonium dihydrogen phosphate, ammonium acid phosphate, or ammonium carbonate. A mixture of phenobarbital-propantheline bromide was selected to demonstrate the utility of the separation and quantification method. The mixture was chromatographed on a phenyl column, using absolute methanol-aqueous 1 percent ammonium dihydrogen phosphate (60:40) (pH 5.85) at a flow rate of 1.4 ml/min. Each determination can be achieved in approximately 15 min with an accuracy of 1-2 percent.", "contents": "Liquid chromatography in pharmaceutical analysis IV: determination of antispasmodic mixtures. Parameters associated with the separation of antianxiety-antispasmodic agents were investigated using high-pressure liquid chromatography. Eight widely prescribed drugs were studied. The compounds were chromatographed on reversed-phase octadecyltrichlorosilane (C18) or diphenyldichlorosilane (phenyl) columns, using mixtures of absolute methanol and distilled water buffered with ammonium dihydrogen phosphate, ammonium acid phosphate, or ammonium carbonate. A mixture of phenobarbital-propantheline bromide was selected to demonstrate the utility of the separation and quantification method. The mixture was chromatographed on a phenyl column, using absolute methanol-aqueous 1 percent ammonium dihydrogen phosphate (60:40) (pH 5.85) at a flow rate of 1.4 ml/min. Each determination can be achieved in approximately 15 min with an accuracy of 1-2 percent."}
{"id": "PMID:239212", "title": "Colorimetric determination of peptide antibiotics: in-process assay of cyclic octapeptidic antibiotics in fermentation broths.", "content": "A spectrophotometric method is presented for monitoring the biosynthesis of a new complex of cyclic octapeptidic antibiotics in fermentation broths. The method is based on the extraction of antibiotic from alkaline broth with butanol. An ion-pair, formed between the octapeptides and bromthymol blue, is extracted into chloroform from a solution buffered to pH 7.5. The absorbance of the colored solution is measured at 420 nm. Results are in good agreement with those obtained by microbiological assay. The method is also applicable to other peptidic antibiotics such as polymyxin B and gramicidin.", "contents": "Colorimetric determination of peptide antibiotics: in-process assay of cyclic octapeptidic antibiotics in fermentation broths. A spectrophotometric method is presented for monitoring the biosynthesis of a new complex of cyclic octapeptidic antibiotics in fermentation broths. The method is based on the extraction of antibiotic from alkaline broth with butanol. An ion-pair, formed between the octapeptides and bromthymol blue, is extracted into chloroform from a solution buffered to pH 7.5. The absorbance of the colored solution is measured at 420 nm. Results are in good agreement with those obtained by microbiological assay. The method is also applicable to other peptidic antibiotics such as polymyxin B and gramicidin."}
{"id": "PMID:239213", "title": "The effects of chronic ganglion blockade and chronic cholinesterase inhibition on the sensitivity of rabbit stomach muscularis to cholinergic and adrenergic agonists.", "content": "The EC50 values, KA values and efficacies (e) of selected agonists have been determined in strips of stomach muscularis from control, chlorisondamine-pretreated and O, O-diethyl S[2(ethylthio)ethyl]phosphodithioate (disulfoton)-pretreated rabbits. Strips from chlorisondamine-pretreated animals were supersensitive to carbachol but normosensitive to phenylephrine; the e but the KA of carbachol was affected by this treatment. The KB of atropine was unchanged. Strips from animals treated with disulfoton were subsensitive to phenylephrine but normosensitive to amidephrine and carbachol; both the e and KA of phenylephrine appeared to be elevated by this pretreatment. The KB of phentolamine remained unchanged. These results indicate that the chlorisondamine-induced supersensitivity is the result of a change beyond the level of the cholinergic receptors. In contradistinction, the subsensitivity to phenylephrine after disulfoton pretreatment may result at least in part, from a qualitative change in the alpha adrenergic receptors in the stomach muscularis.", "contents": "The effects of chronic ganglion blockade and chronic cholinesterase inhibition on the sensitivity of rabbit stomach muscularis to cholinergic and adrenergic agonists. The EC50 values, KA values and efficacies (e) of selected agonists have been determined in strips of stomach muscularis from control, chlorisondamine-pretreated and O, O-diethyl S[2(ethylthio)ethyl]phosphodithioate (disulfoton)-pretreated rabbits. Strips from chlorisondamine-pretreated animals were supersensitive to carbachol but normosensitive to phenylephrine; the e but the KA of carbachol was affected by this treatment. The KB of atropine was unchanged. Strips from animals treated with disulfoton were subsensitive to phenylephrine but normosensitive to amidephrine and carbachol; both the e and KA of phenylephrine appeared to be elevated by this pretreatment. The KB of phentolamine remained unchanged. These results indicate that the chlorisondamine-induced supersensitivity is the result of a change beyond the level of the cholinergic receptors. In contradistinction, the subsensitivity to phenylephrine after disulfoton pretreatment may result at least in part, from a qualitative change in the alpha adrenergic receptors in the stomach muscularis."}
{"id": "PMID:239214", "title": "Release of norepinephrine and dopamine-beta-hydroxylase by nerve stimulation. V. Enhanced release associated with a granular effect of a benzoquinolizine derivative with reserpine-like properties.", "content": "A reserpine-like agent, 2-hydroxy-2-ethyl-3-isobutyl-9,10-dimethoxy-1,2,3,4,6,7,-hexa-hydro-11b-H-benzo[a]quinolizine (BQZ), at concentrations that do not inhibit phosphodiesterase activity, produces a marked increase in the outflow of 3-H-dihydroxyphenyl-ethyleneglycol from the isolated, perfused cat slpeen prelabeled with 3-H-norepinephrine (3-H-NE). The increased intraneuronal levels of catechols probably account for the inhibition of the conversion of 1-minus14C-L-tyrosine to 1-minus14C-L-dopa which is observed in the presence of the drug. In addition, in the presence of 0.9 muM BQZ, there is a 2.5- to 3-fold increase in the nerve stimulation-mediated overflow  of NE, 3-H-NE, total 3-H and dopamine-beta-hydroxylase activity. A highly significant positive correlation was observed between the increase in the spontaneous release of 3-H and the enhanced exocytotic release of transmitter by nerve stimulation. These results suggest that either a primary alteration of the storage granule membrane or the subsequent enhanced intraneuronal levels of NE or NE metabolites may be responsible for the enhanced exocytotic release by nerve stimulation. In the presence of 0.9 muM BQZ, addition of 3 muM cocaine produces an increase in the nerve stimulation-mediated overflow of NE and an inhibition of the formation of 3-H-dihydroxyphenylethyleneglycol. In addition, there is a 20 to 30% decrease in the overflow of 3-H and dopamine-beta-hydroxylase activity and a marked delay in the outflow of the enzyme elicited by nerve stimulation. These results suggested that, in the presence of BQZ, a large fraction of the NE released during nerve stimulation is recaptured into the nerve terminals where it is subsequently metabolized to 3-H-dihydroxyphenylethyleneglycol. The enhanced exocytotic release of NE, the extensive presynaptic metabolism of the recaptured transmitter subsequent to release by nerve stimulation, and inhibition of norepinephrine synthesis all appear to contribute to the accelerated depletion of tissue NE which is observed when the splenic nerves are stimulated in the presence of 0.9 muM BQZ. These results provide an explanation for the accelerated depletion of tissue NE in animals treated with reserpine-like compounds when the sympathetic innervation is intact.", "contents": "Release of norepinephrine and dopamine-beta-hydroxylase by nerve stimulation. V. Enhanced release associated with a granular effect of a benzoquinolizine derivative with reserpine-like properties. A reserpine-like agent, 2-hydroxy-2-ethyl-3-isobutyl-9,10-dimethoxy-1,2,3,4,6,7,-hexa-hydro-11b-H-benzo[a]quinolizine (BQZ), at concentrations that do not inhibit phosphodiesterase activity, produces a marked increase in the outflow of 3-H-dihydroxyphenyl-ethyleneglycol from the isolated, perfused cat slpeen prelabeled with 3-H-norepinephrine (3-H-NE). The increased intraneuronal levels of catechols probably account for the inhibition of the conversion of 1-minus14C-L-tyrosine to 1-minus14C-L-dopa which is observed in the presence of the drug. In addition, in the presence of 0.9 muM BQZ, there is a 2.5- to 3-fold increase in the nerve stimulation-mediated overflow  of NE, 3-H-NE, total 3-H and dopamine-beta-hydroxylase activity. A highly significant positive correlation was observed between the increase in the spontaneous release of 3-H and the enhanced exocytotic release of transmitter by nerve stimulation. These results suggest that either a primary alteration of the storage granule membrane or the subsequent enhanced intraneuronal levels of NE or NE metabolites may be responsible for the enhanced exocytotic release by nerve stimulation. In the presence of 0.9 muM BQZ, addition of 3 muM cocaine produces an increase in the nerve stimulation-mediated overflow of NE and an inhibition of the formation of 3-H-dihydroxyphenylethyleneglycol. In addition, there is a 20 to 30% decrease in the overflow of 3-H and dopamine-beta-hydroxylase activity and a marked delay in the outflow of the enzyme elicited by nerve stimulation. These results suggested that, in the presence of BQZ, a large fraction of the NE released during nerve stimulation is recaptured into the nerve terminals where it is subsequently metabolized to 3-H-dihydroxyphenylethyleneglycol. The enhanced exocytotic release of NE, the extensive presynaptic metabolism of the recaptured transmitter subsequent to release by nerve stimulation, and inhibition of norepinephrine synthesis all appear to contribute to the accelerated depletion of tissue NE which is observed when the splenic nerves are stimulated in the presence of 0.9 muM BQZ. These results provide an explanation for the accelerated depletion of tissue NE in animals treated with reserpine-like compounds when the sympathetic innervation is intact."}
{"id": "PMID:239215", "title": "Effects of reserpine on activities and amounts of tyrosine hydroxylase and dopamine-beta-hydroxylase in catecholamine neuronal systems in rat brain.", "content": "Reserpine (10 mg/kp i.p.) increased the activities of the enzymes tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase, but not dopa decarboxylase, 2- to 3-fold in the nucleus locus ceruleus of rat brain. The TH response was dose-dependent, reached a maximum by 48 hours and recovered by 3 weeks. The increased activities of TH and dopamine-beta-hydroylase were shown by immunotitration with specific antibodies to each enzyme to be due entirely to increased accumulation of specific enzyme protein. At a time when the reserpine-elicited accumulation of TH was increased 300% in the locus ceruleus, activity of the enzyme only increased 20% in hypothalamus and not at all in substantia nigra or caudate nucleus. Reserpine increased the accumulation of TH, primarily in the cell bodies and to a far less degree in the terminals of neurons of locus ceruleus but not in dopaminergic neurons of the nigrostriatal system. The time course of enzyme accumulation parallels that of depletion of monoamines in brain.", "contents": "Effects of reserpine on activities and amounts of tyrosine hydroxylase and dopamine-beta-hydroxylase in catecholamine neuronal systems in rat brain. Reserpine (10 mg/kp i.p.) increased the activities of the enzymes tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase, but not dopa decarboxylase, 2- to 3-fold in the nucleus locus ceruleus of rat brain. The TH response was dose-dependent, reached a maximum by 48 hours and recovered by 3 weeks. The increased activities of TH and dopamine-beta-hydroylase were shown by immunotitration with specific antibodies to each enzyme to be due entirely to increased accumulation of specific enzyme protein. At a time when the reserpine-elicited accumulation of TH was increased 300% in the locus ceruleus, activity of the enzyme only increased 20% in hypothalamus and not at all in substantia nigra or caudate nucleus. Reserpine increased the accumulation of TH, primarily in the cell bodies and to a far less degree in the terminals of neurons of locus ceruleus but not in dopaminergic neurons of the nigrostriatal system. The time course of enzyme accumulation parallels that of depletion of monoamines in brain."}
{"id": "PMID:239216", "title": "Effects of ethanol on neurotransmitter release by rat brain cortical.", "content": "Using a double label technique to preload rat brain cortex slices with different radioactive neurotransmitters (or precursor choline), we have studied the effects of ethanol on the electrically stimulated release of these transmitters. Ethanol inhibited the release of these transmitters, acetylcholine being the most sensitive and occurring at concentrations compatible with moderate to severe intoxication in the rat (IC50 equals 0.17 M). The order of sensitivity to ethanol was acetylcholine greater than serotonin greater than dopamine greater than norepinephrine greater than glutamate greater gamma-aminobutyric acid. Two higher alcohols and two barbiturates were also shown to have a greater inhibitory effect on the stimulated release of acetylcholine than of norepinephrine. The concentrations of all the drugs tested required for 50% inhibition of release of acetylcholine and norepinephrine correlated well with their lipid solubility when corrected for their molecular volumes. The effect of tetrodotoxin and of ouabain on neurotransmitter release was also studied. A comparison of the effects of these two drugs with those of ethanol suggests that the effect of ethanol is consistent with an inhibition of the action potential by this drug, although a specific effect of ethanol on the excitation-coupling process at the synapse cannot by discarded.", "contents": "Effects of ethanol on neurotransmitter release by rat brain cortical. Using a double label technique to preload rat brain cortex slices with different radioactive neurotransmitters (or precursor choline), we have studied the effects of ethanol on the electrically stimulated release of these transmitters. Ethanol inhibited the release of these transmitters, acetylcholine being the most sensitive and occurring at concentrations compatible with moderate to severe intoxication in the rat (IC50 equals 0.17 M). The order of sensitivity to ethanol was acetylcholine greater than serotonin greater than dopamine greater than norepinephrine greater than glutamate greater gamma-aminobutyric acid. Two higher alcohols and two barbiturates were also shown to have a greater inhibitory effect on the stimulated release of acetylcholine than of norepinephrine. The concentrations of all the drugs tested required for 50% inhibition of release of acetylcholine and norepinephrine correlated well with their lipid solubility when corrected for their molecular volumes. The effect of tetrodotoxin and of ouabain on neurotransmitter release was also studied. A comparison of the effects of these two drugs with those of ethanol suggests that the effect of ethanol is consistent with an inhibition of the action potential by this drug, although a specific effect of ethanol on the excitation-coupling process at the synapse cannot by discarded."}
{"id": "PMID:239217", "title": "Effect of hypoxemia on responses to norepinephrine and angiotensin in coronary and muscular vessels.", "content": "The purpose of this study was to determine the relative effects of acute hypoxemia on constrictor responses to norepinephrine and angiotensin in two vascular beds, the coronary and skeletal muscle. The left circumflex coronary and gracilis muscle arteries of anesthetized dogs were perfused at constant flow. Practolol or propranolol was administered to block indirect myocardial effects of norepinephrine on coronary resistance. When Po2 of arterial blood perfusing the coronary and muscle beds was reduced from 101 to 44 mm while systemic Pco2 remained normal, constrictor responses to both norepinephrine and angiotensin were inhibited in coronary vessels but not in muscle vessels. When local Po2 was reduced to 27 mm Hg, inhibition of responses was again observed in the coronary circulation with both drugs; in the muscle, responses to angiotensin but not to norepinephrine were depressed significantly. Since intracoronary infusion of adenosine increased, rather than inhibited, vasoconstrictor responses to angiotensin, it is unlikely that release of adenosine during hypoxemia accounts for inhibition of vasoconstriction in the coronary circulation. Indomethacin did not alter the inhibition of coronary vasoconstrictor responses to angiotensin during hypoxemia, which suggests that releease of prostglandins during htpoxemia is not the primary mechanism for inhibition of coronary vascular responses. When contractions in the gracilis muscle were produced by electrical stimulation, vasconstrictor responses to norepinnephrine were inhibited during hypoxemia. We conclude that depression of constrictor responses by hypoxemia is more pronounced in the coronay circulation than in resting muscle, but when muscle is contracting, vasoconstrictor responses are impaired during hypoxemia.", "contents": "Effect of hypoxemia on responses to norepinephrine and angiotensin in coronary and muscular vessels. The purpose of this study was to determine the relative effects of acute hypoxemia on constrictor responses to norepinephrine and angiotensin in two vascular beds, the coronary and skeletal muscle. The left circumflex coronary and gracilis muscle arteries of anesthetized dogs were perfused at constant flow. Practolol or propranolol was administered to block indirect myocardial effects of norepinephrine on coronary resistance. When Po2 of arterial blood perfusing the coronary and muscle beds was reduced from 101 to 44 mm while systemic Pco2 remained normal, constrictor responses to both norepinephrine and angiotensin were inhibited in coronary vessels but not in muscle vessels. When local Po2 was reduced to 27 mm Hg, inhibition of responses was again observed in the coronary circulation with both drugs; in the muscle, responses to angiotensin but not to norepinephrine were depressed significantly. Since intracoronary infusion of adenosine increased, rather than inhibited, vasoconstrictor responses to angiotensin, it is unlikely that release of adenosine during hypoxemia accounts for inhibition of vasoconstriction in the coronary circulation. Indomethacin did not alter the inhibition of coronary vasoconstrictor responses to angiotensin during hypoxemia, which suggests that releease of prostglandins during htpoxemia is not the primary mechanism for inhibition of coronary vascular responses. When contractions in the gracilis muscle were produced by electrical stimulation, vasconstrictor responses to norepinnephrine were inhibited during hypoxemia. We conclude that depression of constrictor responses by hypoxemia is more pronounced in the coronay circulation than in resting muscle, but when muscle is contracting, vasoconstrictor responses are impaired during hypoxemia."}
{"id": "PMID:239218", "title": "Digitalis toxicity during acute hypoxia in intact conscious dogs.", "content": "Intact, conscious dogs were studied under normal and hypobaric conditions to assess the influence of acute hypoxia on the ability of the animals to tolerate ouabain. Animals were made acutely hypoxic by exposure to hypobaric conditions in a chamber maintained at 446 mm Hg. The ability of the dogs to tolerate ouabain was determined by administering intravenously 7.5 mug/kg of the drug as a loading dose followed by infusion at a rate of 3.0 mug/kg/min to an end point consisting of the development of ventricular or atrioventricular junctional tachycardia. Eight dogs, each acting as its own control, were studied under normoxic and acutely hypoxic conditions. During hypoxia, mean arteriol pO2 decreased to 39 plus or minus 1 (S.E.) mm Hg from 80 plus or minus 1 mm Hg at sea level (P less than .001). The cumulative toxic dose of ouabain was modestly but significantly less (P less than .05) during acute hypoxia (71.7 plus or minus 4.3 mug/kg) compared with normoxic (79.2 plus or minus 4.1 mug/kg) conditions. In these experiments a marked hyperventilation response to ouabain was observed just before onset of toxicity which resulted in a pronounced rise in mean arterial pH (normoxia: 7.39 plus or minus 0.01 to 7.72 plus or minus 0.01; hypoxia: 7.48 plus or minus 0.01 to 7.71 plus or minus 0.04) and fall in pCO2 (normoxia: 41 plus or minus 1 to 14 plus or minus 1 mm Hg; hopoxia: 34 plus or minus 1 to 16 plus or minus 2 mm Hg). Ouabain-induced increases in systemic arterial pressure were comparable in normal and acutely hypoxic animals. Thus, acute hypoxia in unanesthetized dogs exposed to hypobaric conditions results in a decrease of only 10% in the ouabain dose required to produce cardiac arrhythmias, and toxic doses of ouabain produce a striking respiratory alkalosis.", "contents": "Digitalis toxicity during acute hypoxia in intact conscious dogs. Intact, conscious dogs were studied under normal and hypobaric conditions to assess the influence of acute hypoxia on the ability of the animals to tolerate ouabain. Animals were made acutely hypoxic by exposure to hypobaric conditions in a chamber maintained at 446 mm Hg. The ability of the dogs to tolerate ouabain was determined by administering intravenously 7.5 mug/kg of the drug as a loading dose followed by infusion at a rate of 3.0 mug/kg/min to an end point consisting of the development of ventricular or atrioventricular junctional tachycardia. Eight dogs, each acting as its own control, were studied under normoxic and acutely hypoxic conditions. During hypoxia, mean arteriol pO2 decreased to 39 plus or minus 1 (S.E.) mm Hg from 80 plus or minus 1 mm Hg at sea level (P less than .001). The cumulative toxic dose of ouabain was modestly but significantly less (P less than .05) during acute hypoxia (71.7 plus or minus 4.3 mug/kg) compared with normoxic (79.2 plus or minus 4.1 mug/kg) conditions. In these experiments a marked hyperventilation response to ouabain was observed just before onset of toxicity which resulted in a pronounced rise in mean arterial pH (normoxia: 7.39 plus or minus 0.01 to 7.72 plus or minus 0.01; hypoxia: 7.48 plus or minus 0.01 to 7.71 plus or minus 0.04) and fall in pCO2 (normoxia: 41 plus or minus 1 to 14 plus or minus 1 mm Hg; hopoxia: 34 plus or minus 1 to 16 plus or minus 2 mm Hg). Ouabain-induced increases in systemic arterial pressure were comparable in normal and acutely hypoxic animals. Thus, acute hypoxia in unanesthetized dogs exposed to hypobaric conditions results in a decrease of only 10% in the ouabain dose required to produce cardiac arrhythmias, and toxic doses of ouabain produce a striking respiratory alkalosis."}
{"id": "PMID:239219", "title": "Receptor binding and pharmacological activity of opiates in the guinea-pig intestine.", "content": "A comparison was made between the affinities of a wide range of opiate agonists, mixed agonist-antagonists and antagonists for opiate receptor binding sites in the guniea-pig intestine longitudinal muscle and myenteric plexus preparation, and their pharmacological potency in influencing the electrically induced contraction of this in vitro functional system. The relative affinities of drugs and the degree of stereospecificity for intestinal binding sites are closely similar to these properties in the brain. Receptor binding correlates extremely well with pharmacological potency, both for agonists and antagonists, indicating that binding involves pharmacologically relevant opiate receptors. Pharmacological activity correlates best with receptor binding assayed in the presence of sodium.", "contents": "Receptor binding and pharmacological activity of opiates in the guinea-pig intestine. A comparison was made between the affinities of a wide range of opiate agonists, mixed agonist-antagonists and antagonists for opiate receptor binding sites in the guniea-pig intestine longitudinal muscle and myenteric plexus preparation, and their pharmacological potency in influencing the electrically induced contraction of this in vitro functional system. The relative affinities of drugs and the degree of stereospecificity for intestinal binding sites are closely similar to these properties in the brain. Receptor binding correlates extremely well with pharmacological potency, both for agonists and antagonists, indicating that binding involves pharmacologically relevant opiate receptors. Pharmacological activity correlates best with receptor binding assayed in the presence of sodium."}
{"id": "PMID:239220", "title": "Postnatal elevation of brain tyrosine hydroxylase activity, without concurrent increases in steady-state catecholamine levels, resulting from dl-alpha-methylparatyrosine administration during embryonic development.", "content": "Increased specific activity of tyrosine hydroxylase (TH) in the brains of embryonic and 29-day-old chickens results from exposure to reserpine during the early stages of embryogenesis. We have also reported significant increases in the steady-state concentrations of catecholamines (CAs) in the brains of these 29-day-old chickens, suggesting permanent alterations in the control mechanisms during a critical period of development. The specificity of embryonic CA depletion in the above findings was examined usind dl-alpha-methyl-para-tyrosine (AMPT) as a depleting agent. AMPT, injected in varying doses into the yolk sac of fertilized chicken eggs prior to incubation, caused embryonic CA depletion by day 10 of embryogenesis but repletion had occurred by 20 days of embryogenesis. TH activity in whole brain and brain parts was elevated in a dose-related fashion at 29 days postnatally by AMPT. However, no changes in steady-state CA levels in whole brain were observed at this time after AMPT. Differences in the responses to reserpine and AMPT are discussed with respect to their pharmacological actions. The data support the contention that early embryonic CA depletion can result in long-term increases in TH activity postnatally, but steady-state levels of product need not necessarily be altered.", "contents": "Postnatal elevation of brain tyrosine hydroxylase activity, without concurrent increases in steady-state catecholamine levels, resulting from dl-alpha-methylparatyrosine administration during embryonic development. Increased specific activity of tyrosine hydroxylase (TH) in the brains of embryonic and 29-day-old chickens results from exposure to reserpine during the early stages of embryogenesis. We have also reported significant increases in the steady-state concentrations of catecholamines (CAs) in the brains of these 29-day-old chickens, suggesting permanent alterations in the control mechanisms during a critical period of development. The specificity of embryonic CA depletion in the above findings was examined usind dl-alpha-methyl-para-tyrosine (AMPT) as a depleting agent. AMPT, injected in varying doses into the yolk sac of fertilized chicken eggs prior to incubation, caused embryonic CA depletion by day 10 of embryogenesis but repletion had occurred by 20 days of embryogenesis. TH activity in whole brain and brain parts was elevated in a dose-related fashion at 29 days postnatally by AMPT. However, no changes in steady-state CA levels in whole brain were observed at this time after AMPT. Differences in the responses to reserpine and AMPT are discussed with respect to their pharmacological actions. The data support the contention that early embryonic CA depletion can result in long-term increases in TH activity postnatally, but steady-state levels of product need not necessarily be altered."}
{"id": "PMID:239221", "title": "Effect of thioridazine, clozapine and other antipsychotics on the kinetic state of tyrosine hydroxylase and on the turnover rate of dopamine in striatum and nucleus accumbens.", "content": "In rats, a single injection of antipsychotic drugs produced a transitory change in the kinetic state of tyrosine hydroxylase (TH) in striatum and nucleus accumbens. The affinity of TH for 2-amino-4-hydoxy-6,7-dimethyl-5,6,7,8-tetrahydropterine (DMPH4) and the Vmax with respect ot tyrosine were increased. The relative potencies of anti-psychotics to change the kinetics of TH in striatum and nucleus accumbens when injected into rats were measured in the presence of 0.4 mM DMPH4. The doses of methiothepin, pimozide and halopridol which increased the affinity for DMPH4 of striatal TH were lower than those required to produce a similar change in nucleus accumbens. In contrast, thioridazine and clozapine were more effective in nucleus accumbens than in striatum. Chlorpromazine was equally active in these two tissues. Haloperidol increased the turnover rate of dopamine in striatum with doses that are relatively smaller than those required in the nucleus accumbens. Clozapine was more active in increasing turnover rate of dopamine in nucleus accumbens; the activity of chlorpromazine in these two tissues was equal. These results suggest that antipsychotics with high incidence of extrapyramidal side effects affect the nigrostriatal dopaminergic pathway selectively.", "contents": "Effect of thioridazine, clozapine and other antipsychotics on the kinetic state of tyrosine hydroxylase and on the turnover rate of dopamine in striatum and nucleus accumbens. In rats, a single injection of antipsychotic drugs produced a transitory change in the kinetic state of tyrosine hydroxylase (TH) in striatum and nucleus accumbens. The affinity of TH for 2-amino-4-hydoxy-6,7-dimethyl-5,6,7,8-tetrahydropterine (DMPH4) and the Vmax with respect ot tyrosine were increased. The relative potencies of anti-psychotics to change the kinetics of TH in striatum and nucleus accumbens when injected into rats were measured in the presence of 0.4 mM DMPH4. The doses of methiothepin, pimozide and halopridol which increased the affinity for DMPH4 of striatal TH were lower than those required to produce a similar change in nucleus accumbens. In contrast, thioridazine and clozapine were more effective in nucleus accumbens than in striatum. Chlorpromazine was equally active in these two tissues. Haloperidol increased the turnover rate of dopamine in striatum with doses that are relatively smaller than those required in the nucleus accumbens. Clozapine was more active in increasing turnover rate of dopamine in nucleus accumbens; the activity of chlorpromazine in these two tissues was equal. These results suggest that antipsychotics with high incidence of extrapyramidal side effects affect the nigrostriatal dopaminergic pathway selectively."}
{"id": "PMID:239222", "title": "The activity of tyrosine hydroxylase in intact adrenergic neurons of the mouse vas deferens.", "content": "A procedure is described for measuring the activity of tyrosine hydroxylase in the intact adrenergic neurons of the mouse vas deferens. In this procedure, the L-dopa-1-14C which is formed from L-tyrosine-1-14C by the action of tyrosine hydroxylase is selectively and quantitatively decarboxylated by endogenous aromatic-L-amino acid decarboxylase. Although considerable tyrosine hydroxylase activity can be demonstrated with the intact mouse vas deferens in the absence of exogenous tetrahydropterin cofactor, the addition of 2-amino-4-hydroxy-6,7-dimethyltetrahydropteridine results in increased activity. Exogenous norepinephrine inhibits the activity of tyrosine hydroxylase in the intact mouse vas deferens and this inhibitory effect is competitively antagonized by 2-amino-4-hydroxy-6,7-dimethyltetrahydropteridine. When the vesicular catecholamine uptake mechanism is blocked by treatment of mice with 5 mg/kg of reserpine 24 hours prior to sacrifice, the activity of tyrosine hydroxylase in intact vas deferens is reduced and the inhibitory effect of exogenous norepinephrine is enhanced. Inhibition of monoamine oxidase with 0.15 mM pargyline does not affect the activity of tyrosine hydroxylase in the intact mouse vas deferens when the vesicular catecholamine uptake mechanism is intact but has a pronounced inhibitory effect following reserpine treatment. These observations lend further support to the conclusion that the activity of tyrosine hydroxylase in the intact adrenergic neuron is inversely related to the catecholamine concentration within an extravesicular pool. They also suggest that the catecholamines tend to accumulate within this extravesicular pool and thus become accessible to the action of monoamine oxidase when the vesicular uptake mechanism is inactivated or when the vesicular stores are filled to capacity.", "contents": "The activity of tyrosine hydroxylase in intact adrenergic neurons of the mouse vas deferens. A procedure is described for measuring the activity of tyrosine hydroxylase in the intact adrenergic neurons of the mouse vas deferens. In this procedure, the L-dopa-1-14C which is formed from L-tyrosine-1-14C by the action of tyrosine hydroxylase is selectively and quantitatively decarboxylated by endogenous aromatic-L-amino acid decarboxylase. Although considerable tyrosine hydroxylase activity can be demonstrated with the intact mouse vas deferens in the absence of exogenous tetrahydropterin cofactor, the addition of 2-amino-4-hydroxy-6,7-dimethyltetrahydropteridine results in increased activity. Exogenous norepinephrine inhibits the activity of tyrosine hydroxylase in the intact mouse vas deferens and this inhibitory effect is competitively antagonized by 2-amino-4-hydroxy-6,7-dimethyltetrahydropteridine. When the vesicular catecholamine uptake mechanism is blocked by treatment of mice with 5 mg/kg of reserpine 24 hours prior to sacrifice, the activity of tyrosine hydroxylase in intact vas deferens is reduced and the inhibitory effect of exogenous norepinephrine is enhanced. Inhibition of monoamine oxidase with 0.15 mM pargyline does not affect the activity of tyrosine hydroxylase in the intact mouse vas deferens when the vesicular catecholamine uptake mechanism is intact but has a pronounced inhibitory effect following reserpine treatment. These observations lend further support to the conclusion that the activity of tyrosine hydroxylase in the intact adrenergic neuron is inversely related to the catecholamine concentration within an extravesicular pool. They also suggest that the catecholamines tend to accumulate within this extravesicular pool and thus become accessible to the action of monoamine oxidase when the vesicular uptake mechanism is inactivated or when the vesicular stores are filled to capacity."}
{"id": "PMID:239223", "title": "The absence of renal bicarbonate reabsorption maxima during carbonic anhydrase inhibition.", "content": "Present studies were performed to examine the effect of carbonic anhydrase inhibition on bicarbonate reabsorption under experimental conditions where extracellular fluid volume expansion was minimized. The data showed no tubular maximum for bicarbonate reabsorption in the normal state or after carbonic anhydrase inhibition. The data support a model which assumes that the bicarbonate reabsorption is accomplished by two processes. One process is independent of protonation from H+ secretion into the tubule and probably involves reabsorption of bicarbonate ion as such. This process has an unlimited capacity for reabsorption of bicarbonate. The contribution of this process increases with an increase in plasma bicarbonate. The second process is dependent on protonation, through the intracellular hydration of carbon dioxide. The relative contribution, through the intracellular hydration of carbon dioxide. The relative contribution of this process is normally about 33% and decreases with increased plasma bicarbonate.", "contents": "The absence of renal bicarbonate reabsorption maxima during carbonic anhydrase inhibition. Present studies were performed to examine the effect of carbonic anhydrase inhibition on bicarbonate reabsorption under experimental conditions where extracellular fluid volume expansion was minimized. The data showed no tubular maximum for bicarbonate reabsorption in the normal state or after carbonic anhydrase inhibition. The data support a model which assumes that the bicarbonate reabsorption is accomplished by two processes. One process is independent of protonation from H+ secretion into the tubule and probably involves reabsorption of bicarbonate ion as such. This process has an unlimited capacity for reabsorption of bicarbonate. The contribution of this process increases with an increase in plasma bicarbonate. The second process is dependent on protonation, through the intracellular hydration of carbon dioxide. The relative contribution, through the intracellular hydration of carbon dioxide. The relative contribution of this process is normally about 33% and decreases with increased plasma bicarbonate."}
{"id": "PMID:239224", "title": "Molecular mechanisms in the actions of morphine and viminol (R2) on rat striatum.", "content": "Analgesic doses of morphine and viminol R2 increase the turnover rate of dopamine (DA) in rat striatum but fail to increase the striatal concentration of adenosine 3',5'-monophosphate (cAMP) or the affinity of tyrosine hydroxylase (TH) for the pteridine cofactor. When morphine is added to striatal homogenates, it changes neither the basal activity of adenylate cyclase nor the enzyme activation by DA. Similarly to morphine, haloperidol enhances the turnover rate of striatal DA, but unlike morphine it increases the affinity of TH for the pteridine cofactor and blocks the in vitro activation of striatal adenylacte cyclase by DA. Morphine (52 mumol/kg i.p.), viminol R2 (7 mumol/kg i.p.) or haloperidol (2.6 mumol/kg i.p.) fails to increase the striatal cAMP contrations. However (+)-amphetamine (4.8 mumol/kg i.p.) increases DA turnover rate and the striatal cAMP content, but, in doses up to 12.8 mumol/kg i.p., it fails to change the affinity of TH for the pteridine cofactor. This study shows that although (+)-amphetamine, haloperidol and morphine increase the turnover rate of striatal DA each drug possesses a specific profile in its action on molecular mechanisms that control the function of striatal dopaminergic synapses.", "contents": "Molecular mechanisms in the actions of morphine and viminol (R2) on rat striatum. Analgesic doses of morphine and viminol R2 increase the turnover rate of dopamine (DA) in rat striatum but fail to increase the striatal concentration of adenosine 3',5'-monophosphate (cAMP) or the affinity of tyrosine hydroxylase (TH) for the pteridine cofactor. When morphine is added to striatal homogenates, it changes neither the basal activity of adenylate cyclase nor the enzyme activation by DA. Similarly to morphine, haloperidol enhances the turnover rate of striatal DA, but unlike morphine it increases the affinity of TH for the pteridine cofactor and blocks the in vitro activation of striatal adenylacte cyclase by DA. Morphine (52 mumol/kg i.p.), viminol R2 (7 mumol/kg i.p.) or haloperidol (2.6 mumol/kg i.p.) fails to increase the striatal cAMP contrations. However (+)-amphetamine (4.8 mumol/kg i.p.) increases DA turnover rate and the striatal cAMP content, but, in doses up to 12.8 mumol/kg i.p., it fails to change the affinity of TH for the pteridine cofactor. This study shows that although (+)-amphetamine, haloperidol and morphine increase the turnover rate of striatal DA each drug possesses a specific profile in its action on molecular mechanisms that control the function of striatal dopaminergic synapses."}
{"id": "PMID:239225", "title": "Modification by lithium of transmitter release at the neuromuscular junction of the frog.", "content": "Complete or partial replacement of Na+ by Li+ resulted in a progressively developing increase in the amplitude and quantal content of end-plate potentials of the frog neuromuscular junction. Analysis of frequency facilitation curves and estimations of the binomial parameters of release indicate that Li+ caused an increase in the probability of transmitter release. Li+ also caused a time dependent increase in the frequency of miniature end-plate potentials. The responsiveness of the miniature end-plate potentials to Li+ was depressed by elevated Ca++ and enhanced by elevated K+. Collectively, the effects of Li+ on transmitter release can be attributed to the accumulation by the nerve terminals of Li+ resulting on an increased level of intracellular Ca++.", "contents": "Modification by lithium of transmitter release at the neuromuscular junction of the frog. Complete or partial replacement of Na+ by Li+ resulted in a progressively developing increase in the amplitude and quantal content of end-plate potentials of the frog neuromuscular junction. Analysis of frequency facilitation curves and estimations of the binomial parameters of release indicate that Li+ caused an increase in the probability of transmitter release. Li+ also caused a time dependent increase in the frequency of miniature end-plate potentials. The responsiveness of the miniature end-plate potentials to Li+ was depressed by elevated Ca++ and enhanced by elevated K+. Collectively, the effects of Li+ on transmitter release can be attributed to the accumulation by the nerve terminals of Li+ resulting on an increased level of intracellular Ca++."}
{"id": "PMID:239226", "title": "The effects of maternal hypercapnia on foetal oxygenation and uterine blood flow in the pig.", "content": "1. The purpose of this investigation was to determine the effects of maternal hyperoxaemia and hypercapnia on the uterine vascular bed and foetal oxygenation in the large white sow at 80-90 days gestation. 2. When maternal hyperoxaemia was induced with 100% oxygen, there was a highly significant rise in the maternal arterial oxygen tension, but no other significant blood gas or vascular changes were observed. 3. When mild maternal hypercapnia was superimposed on maternal hyperoxaemia (oxygen plus 6% carbon dioxide), the oxygen tension and saturation of both the maternal uterine venous and foetal umbilical venous bloods were found when severe hypercapnia was induced (oxygen plus 50% carbon dioxide) but in this case all blood samples showed dramatic changes in PCO2 and pH. These changes were accompanied by an increase in the systemic blood pressure and uterine blood flow, and a decrease in uterine vascular resistance. 4. When mild hypercapnia was induced without hyperoxaemia (air plus 5% carbon dioxide) significant increases were recorded in the oxygen tension and saturation of uterine venous and foetal umbilical venous bloods. Systemic and uterine vascular resistance fell. 5. It was concluded that the increased foetal oxygen tension during maternal hypercapnia was the result of the increased uterine blood flow and greater mass delivery of oxygen to the placenta, so that once the oxygen requirements of the placental tissues themselves were exceeded there would be an increased oxygen gradient at the site of gas exchange. 6. Carbon dioxide concentration in arterial blood plays an important role in determining blood flow through the pregnant uterus in the sow.", "contents": "The effects of maternal hypercapnia on foetal oxygenation and uterine blood flow in the pig. 1. The purpose of this investigation was to determine the effects of maternal hyperoxaemia and hypercapnia on the uterine vascular bed and foetal oxygenation in the large white sow at 80-90 days gestation. 2. When maternal hyperoxaemia was induced with 100% oxygen, there was a highly significant rise in the maternal arterial oxygen tension, but no other significant blood gas or vascular changes were observed. 3. When mild maternal hypercapnia was superimposed on maternal hyperoxaemia (oxygen plus 6% carbon dioxide), the oxygen tension and saturation of both the maternal uterine venous and foetal umbilical venous bloods were found when severe hypercapnia was induced (oxygen plus 50% carbon dioxide) but in this case all blood samples showed dramatic changes in PCO2 and pH. These changes were accompanied by an increase in the systemic blood pressure and uterine blood flow, and a decrease in uterine vascular resistance. 4. When mild hypercapnia was induced without hyperoxaemia (air plus 5% carbon dioxide) significant increases were recorded in the oxygen tension and saturation of uterine venous and foetal umbilical venous bloods. Systemic and uterine vascular resistance fell. 5. It was concluded that the increased foetal oxygen tension during maternal hypercapnia was the result of the increased uterine blood flow and greater mass delivery of oxygen to the placenta, so that once the oxygen requirements of the placental tissues themselves were exceeded there would be an increased oxygen gradient at the site of gas exchange. 6. Carbon dioxide concentration in arterial blood plays an important role in determining blood flow through the pregnant uterus in the sow."}
{"id": "PMID:239228", "title": "Intracellular pH and distribution of weak acids across cell membranes. A study of D- and L-lactate and of DMO in rat diaphragm.", "content": "1. The steady-state distribution ratios of D- and L-lactate between fibre water and external fluid were measured in 'intact' rat hemidiaphragm preparations exposed for 2-5 hr to a variety of solutions of normal ionic strength and osmolarity. The studies were designed to minimize the effects, on these distributions, of conversion of lactate and of generation of lactic acid by the muscle. 2. At D-lactate concentrations between 2.3 and 118 mM, at normal pH and PCO2, the D-lactate distribution ratio, obtained from the distribution of [2-(3)H]D-lactate was independent of concentration; it averaged 0.349. As the concentration of D-lactate was reduced below 2.3 mM, its distribution ratio progressively fell to less than 0.1. 3. Radiochromatograms of extracts of incubated muscle showed that the tritium label was not attached to substances other than lactate. 4. At L-lactate concentrations of 59 and 108 mM, at normal pH and PCO2, the average L-lactate distribution ratios, obtained by enzymatic analysis, were respectively 0.395 and 0392. 5. At 19-89 mM D-lactate, depolarizing the muscle fibres by high K(49-127 mM), at normal pH, PCO2, and [K]0[Cl]0 product, only slightly affected the D-lactate distribution ratio which averaged 0.405. 6. The D-lactate distribution ratio and intracellular pH (pHi), obtained with the DMO method (5,5-dimethyl-2,4-oxazolidinedione), were measured in thirty sets of studies after exposure of the muscle to solutions buffered to pH values ranging between 5.99 and 8.13, and containing 18.5-118 mM D-lactate and 6-129 mM-K. 7. The relation between the distribution ratios of D-lactate ([TL]i/[TL]O) and of H ions ([Ho/[H]i) in these studies could be expressed by [TL]i/[T]O = 0.646 [H]o/[H]i+0.056. 8. It was concluded that it is predominantly the undissociated lactic acid molecules, rather than the much more numerous lactate ions, which permeate the fibre membrane; and that the steady-state lactate distribution ratio is determined by the transmembrane pH gradient, and not by membrane potential. 9. The expression of the steady-state lactate distribution ratio as function of relative membrane permeabilities of lactic acid molecule and lactate ion, membrane voltage, and internal and external H ion concentrations indicates that a finite permeability to the ion, three or four orders of magnitude less than that to the molecule, is compatible with the experimental data. When both ion and molecule of any weak acid are permeable, they act as a carrier system for the movement of protons down their electrochemical gradient. 10. Near-maintenance of pHi in the face of high fibre D-lactate (19-44 mM) and DMO (8-42 mM) indicates stimulation of proton extrusion by acid loans. 11. This extrusion is insensitive to ouabain, as judged from the lack of effect of the drug of pHi with acid loading.", "contents": "Intracellular pH and distribution of weak acids across cell membranes. A study of D- and L-lactate and of DMO in rat diaphragm. 1. The steady-state distribution ratios of D- and L-lactate between fibre water and external fluid were measured in 'intact' rat hemidiaphragm preparations exposed for 2-5 hr to a variety of solutions of normal ionic strength and osmolarity. The studies were designed to minimize the effects, on these distributions, of conversion of lactate and of generation of lactic acid by the muscle. 2. At D-lactate concentrations between 2.3 and 118 mM, at normal pH and PCO2, the D-lactate distribution ratio, obtained from the distribution of [2-(3)H]D-lactate was independent of concentration; it averaged 0.349. As the concentration of D-lactate was reduced below 2.3 mM, its distribution ratio progressively fell to less than 0.1. 3. Radiochromatograms of extracts of incubated muscle showed that the tritium label was not attached to substances other than lactate. 4. At L-lactate concentrations of 59 and 108 mM, at normal pH and PCO2, the average L-lactate distribution ratios, obtained by enzymatic analysis, were respectively 0.395 and 0392. 5. At 19-89 mM D-lactate, depolarizing the muscle fibres by high K(49-127 mM), at normal pH, PCO2, and [K]0[Cl]0 product, only slightly affected the D-lactate distribution ratio which averaged 0.405. 6. The D-lactate distribution ratio and intracellular pH (pHi), obtained with the DMO method (5,5-dimethyl-2,4-oxazolidinedione), were measured in thirty sets of studies after exposure of the muscle to solutions buffered to pH values ranging between 5.99 and 8.13, and containing 18.5-118 mM D-lactate and 6-129 mM-K. 7. The relation between the distribution ratios of D-lactate ([TL]i/[TL]O) and of H ions ([Ho/[H]i) in these studies could be expressed by [TL]i/[T]O = 0.646 [H]o/[H]i+0.056. 8. It was concluded that it is predominantly the undissociated lactic acid molecules, rather than the much more numerous lactate ions, which permeate the fibre membrane; and that the steady-state lactate distribution ratio is determined by the transmembrane pH gradient, and not by membrane potential. 9. The expression of the steady-state lactate distribution ratio as function of relative membrane permeabilities of lactic acid molecule and lactate ion, membrane voltage, and internal and external H ion concentrations indicates that a finite permeability to the ion, three or four orders of magnitude less than that to the molecule, is compatible with the experimental data. When both ion and molecule of any weak acid are permeable, they act as a carrier system for the movement of protons down their electrochemical gradient. 10. Near-maintenance of pHi in the face of high fibre D-lactate (19-44 mM) and DMO (8-42 mM) indicates stimulation of proton extrusion by acid loans. 11. This extrusion is insensitive to ouabain, as judged from the lack of effect of the drug of pHi with acid loading."}
{"id": "PMID:239229", "title": "A branched-chain amino acid aminotransferase from the rumen ciliate genus Entodinium.", "content": "A branched-chain amino acid aminotransferase was extracted from rumen ciliates of the genus Entodinium and was partially purified by Sephadex G-200, DEAE-cellulose and DEAE-Sephasex A-50 column chromatography. The purified enzyme was active only with leucine, isoleucine and valine, and required pyridoxal phosphate as cofactor. The amino acids competed with each other as substrates. The enzyme had optimal activity at pH 6.0 in phosphate buffer. The Km values for the substrates and cofactor are as follows: 1.66 for leucine; 0.90 for isoleucine; 0.79 for valine; 0.29 mM for alpha-ketoglutarate; and 0.1 muM for pyridoxal phosphate. Enzyme activity was inhibited by rho-chloromercuribenzoate and HgCl2. Gel filtration indicated the enzyme to have a molecular weight of 34,000.", "contents": "A branched-chain amino acid aminotransferase from the rumen ciliate genus Entodinium. A branched-chain amino acid aminotransferase was extracted from rumen ciliates of the genus Entodinium and was partially purified by Sephadex G-200, DEAE-cellulose and DEAE-Sephasex A-50 column chromatography. The purified enzyme was active only with leucine, isoleucine and valine, and required pyridoxal phosphate as cofactor. The amino acids competed with each other as substrates. The enzyme had optimal activity at pH 6.0 in phosphate buffer. The Km values for the substrates and cofactor are as follows: 1.66 for leucine; 0.90 for isoleucine; 0.79 for valine; 0.29 mM for alpha-ketoglutarate; and 0.1 muM for pyridoxal phosphate. Enzyme activity was inhibited by rho-chloromercuribenzoate and HgCl2. Gel filtration indicated the enzyme to have a molecular weight of 34,000."}
{"id": "PMID:239231", "title": "Mixed IgM-IgG cryoglobulinemia terminating in polyarteritis nodosa.", "content": "A case of mixed IgM-IgG cryoglobulinemia and polyarteritis nodosa is described. The patient exhibited non-deforming arthritis, Raynaud's phenomena, cutaneous vasculitis, and a sensory neuropathy.. The terminal phase of the illness was characterized by hypertension and retroperitoneal hemorrhage, with widespread large vessel arteritis. The isolated cryoprecipitate contained IgM, IgG, and C3 and possessed rheumatoid factor activity. Mild reduction in serum complement (CH50 and C3) was noted on one occasion. The evidence that these cryoprecipitable proteins may be acting as immune complexes and contributing to the arterial lesions is reviewed.", "contents": "Mixed IgM-IgG cryoglobulinemia terminating in polyarteritis nodosa. A case of mixed IgM-IgG cryoglobulinemia and polyarteritis nodosa is described. The patient exhibited non-deforming arthritis, Raynaud's phenomena, cutaneous vasculitis, and a sensory neuropathy.. The terminal phase of the illness was characterized by hypertension and retroperitoneal hemorrhage, with widespread large vessel arteritis. The isolated cryoprecipitate contained IgM, IgG, and C3 and possessed rheumatoid factor activity. Mild reduction in serum complement (CH50 and C3) was noted on one occasion. The evidence that these cryoprecipitable proteins may be acting as immune complexes and contributing to the arterial lesions is reviewed."}
{"id": "PMID:239232", "title": "Synthesis and biological evaluation of some 10-substituted 2,3-dihydroimidazo[2,1-b]quinazolin-5(10H)-ones, a new class of bronchodilators.", "content": "On treatment of N-substituted isatoic anhydrides with 2-methylmercaptoimidazolines, 10-substituted imidazo[2,1-b]quinazolin-5(10H)-ones are obtained. Several members of this class exhibited pronounced broncholytic activity. The structure-activity relationships (based on results obtained in the guinea pig histamine aerosol test) of these nonsympathomimetic bronchodilators are discussed. In addition, the detailed pharmacological evaluation of two analogs found to be five to ten times more active than theophyline as bronchodilators without having central nervous system or cardiovascular side effects is described.", "contents": "Synthesis and biological evaluation of some 10-substituted 2,3-dihydroimidazo[2,1-b]quinazolin-5(10H)-ones, a new class of bronchodilators. On treatment of N-substituted isatoic anhydrides with 2-methylmercaptoimidazolines, 10-substituted imidazo[2,1-b]quinazolin-5(10H)-ones are obtained. Several members of this class exhibited pronounced broncholytic activity. The structure-activity relationships (based on results obtained in the guinea pig histamine aerosol test) of these nonsympathomimetic bronchodilators are discussed. In addition, the detailed pharmacological evaluation of two analogs found to be five to ten times more active than theophyline as bronchodilators without having central nervous system or cardiovascular side effects is described."}
{"id": "PMID:239233", "title": "Synthesis and biological evaluation of fragmented derivatives of tetrahydroisoquinolines. 2. Trimetoquinol studies.", "content": "The synthesis of N-(3',4',5'-trimethoxyphenylethyl)-3,4-dihydroxyphenylethylamine (2) and 1-(3,4,5-trimethoxybenzyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (1) is presented. Comparative pharmacological effects of the optical isomers of 1 and compound 2 are reported in guinea pig atria, rat adipose tissue, guinea pig trachea, and guinea pig aortic strip preparations. In the beta-adrenoreceptor preparations, (-)-1 was shown to be more potent than (+)-1 or 2. Racemic 1 and 2 were shown to have equal alpha-antagonist properties in the inhibition of norepinephrine-induced contractions of guinea pig aorta.", "contents": "Synthesis and biological evaluation of fragmented derivatives of tetrahydroisoquinolines. 2. Trimetoquinol studies. The synthesis of N-(3',4',5'-trimethoxyphenylethyl)-3,4-dihydroxyphenylethylamine (2) and 1-(3,4,5-trimethoxybenzyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (1) is presented. Comparative pharmacological effects of the optical isomers of 1 and compound 2 are reported in guinea pig atria, rat adipose tissue, guinea pig trachea, and guinea pig aortic strip preparations. In the beta-adrenoreceptor preparations, (-)-1 was shown to be more potent than (+)-1 or 2. Racemic 1 and 2 were shown to have equal alpha-antagonist properties in the inhibition of norepinephrine-induced contractions of guinea pig aorta."}
{"id": "PMID:239234", "title": "3-Substituted 2-formylquinoxaline 1,4-dioxides.", "content": "The methylnitrone of 3-methyl-1,4-dioxidoquinoxaline-2-carboxaldehyde (1) has been exceptional antibacterial activity in vivo. Derivatives of 3-hydroxymethyl-1,4-dioxidoquinoxaline-2-carboxaldehyde and 3-acetoxymethyl-1,4-dioxidoquinoxaline-2-carboxaldehyde were prepared. Several of these compounds were found to be antibacterial agents of the same order of activity as I.", "contents": "3-Substituted 2-formylquinoxaline 1,4-dioxides. The methylnitrone of 3-methyl-1,4-dioxidoquinoxaline-2-carboxaldehyde (1) has been exceptional antibacterial activity in vivo. Derivatives of 3-hydroxymethyl-1,4-dioxidoquinoxaline-2-carboxaldehyde and 3-acetoxymethyl-1,4-dioxidoquinoxaline-2-carboxaldehyde were prepared. Several of these compounds were found to be antibacterial agents of the same order of activity as I."}
{"id": "PMID:239235", "title": "Microelectrometric titration measurement of the pKa's and partition and drug distribution coefficients of narcotics and narcotic antagonists and their pH and temperature dependence.", "content": "The pKa's, partition coefficients, and drug distribution coefficients (apparent partition coefficients) have been investigated for a number of narcotics and, where possible, for their congener narcotic antagonists.  These studies were carried out by a microelectrometric titration technique as a function of temperature and pH.  This method enables one to determine not only the dissociation constants to deconvolute overlapping pKa's, but also to determine the solubilities of oil-water distribution of these various drugs.  The drug distribution coefficients displayed marked sensitivity to pH at values which span the range of attainable human physiological pH values.  This has significant pharmacological implications for proper choice and scaling of drug dosages under various clinical situations.  The partition coefficients and drug distribution coefficients were noticeably different at 20 degrees (where such measurements are customarily made) than at 37 degrees (body temperature).  Furthermore, various drugs exhibit very nonequivalent increases in drug distribution coefficients with increasing temperature, ranginf from 21% for morephine to 200% for naltrexone.  This nonregularity indicates that it will not be valid to extrapolate by any constant factor the measurements made at lower temperatures.  Even the true partition coefficients increase with temperature from 20 degrees to 37 degrees.  There is more of a difference in the drug distribution coefficients for naloxone and naltrexone than might have been expected from the similarities in their structures with naltrexone being significantly less lipophilic than naloxone.  This would imply that this would lead to naloxone having a more rapid onset for antagonist activity and likewise a shorter duration of action than naltrexone.", "contents": "Microelectrometric titration measurement of the pKa's and partition and drug distribution coefficients of narcotics and narcotic antagonists and their pH and temperature dependence. The pKa's, partition coefficients, and drug distribution coefficients (apparent partition coefficients) have been investigated for a number of narcotics and, where possible, for their congener narcotic antagonists.  These studies were carried out by a microelectrometric titration technique as a function of temperature and pH.  This method enables one to determine not only the dissociation constants to deconvolute overlapping pKa's, but also to determine the solubilities of oil-water distribution of these various drugs.  The drug distribution coefficients displayed marked sensitivity to pH at values which span the range of attainable human physiological pH values.  This has significant pharmacological implications for proper choice and scaling of drug dosages under various clinical situations.  The partition coefficients and drug distribution coefficients were noticeably different at 20 degrees (where such measurements are customarily made) than at 37 degrees (body temperature).  Furthermore, various drugs exhibit very nonequivalent increases in drug distribution coefficients with increasing temperature, ranginf from 21% for morephine to 200% for naltrexone.  This nonregularity indicates that it will not be valid to extrapolate by any constant factor the measurements made at lower temperatures.  Even the true partition coefficients increase with temperature from 20 degrees to 37 degrees.  There is more of a difference in the drug distribution coefficients for naloxone and naltrexone than might have been expected from the similarities in their structures with naltrexone being significantly less lipophilic than naloxone.  This would imply that this would lead to naloxone having a more rapid onset for antagonist activity and likewise a shorter duration of action than naltrexone."}
{"id": "PMID:239236", "title": "Synthesis and biological activity of spin-labeled analogs of biotin, hexamethonium, decamethonium, dichlorisoproterenol, and propranolol.", "content": "Spin-labeled analogs of biotin (vitamin H), hexamethonium, decamethonium, dichlorisoproterenol, propranolol, and primaquine containing the nitroxide free radical have been synthesized and tested for biological activity. The four spin-labeled analogs of biotin, 4-biotinamido-2,2,6,6-tetramethyl-1-piperidinyloxy (IV), 3-biotinamido-2,2,5,5-tetramethyl-1-pyrrolidinyloxy (V), 3-biotinamidomethyl-2,2,5,5-tetramethyl-1-pyrrolidinyloxy (VI), and 4-(biotinylglycyl)amino-2,2,6,6-tetramethyl-1-piperidinyloxy (VII), all interacted with avidin, a specific biotin binding protein found in raw egg white, at the same sites as did biotin itself. An unsymmetrical decamethonium spin label (XVIII) in which one of the quaternary methyl groups had been replaced by the 4-(2,2,6,6-tetramethyl-1-piperidinyloxy) moiety was 13 times more potent as an inhibitor of Torpedo californica acetylcholinesterase than the parent drug. The symmetrical decamethonium (XVI) and hexamethonium (XIV) spin labels were 18 and 1.8 times as active as decamethonium in the same assay system. The substitution of the 4-(2,2,6,6-tetramethyl-1-piperidinyloxy) group for the isopropyl groups of beta-adrenergic blocking drugs dichlorisoproterenol and propranolol, to give spin labels XXI and XXII, caused a 45 and 54% reduction, respectively, in the ability of these compounds to inhibit the isoproterenol-stimulated activity of rat fat cell membranes. Finally, modification of primaquine by the introduction of the 4-(2,2,6,6-tetramethyl-1-piperidinyloxy) substituent into the amino group of the butyl side chain completely abolished the ability of the drug to bind to nuclei acids. These results suggest that the incorporation of the nitroxide group into drug molecules may be a useful approach to the synthesis of more specific spin labels for biological systems, such as egg white avidin, acetylcholinesterase, and the beta-adrenergic receptor.", "contents": "Synthesis and biological activity of spin-labeled analogs of biotin, hexamethonium, decamethonium, dichlorisoproterenol, and propranolol. Spin-labeled analogs of biotin (vitamin H), hexamethonium, decamethonium, dichlorisoproterenol, propranolol, and primaquine containing the nitroxide free radical have been synthesized and tested for biological activity. The four spin-labeled analogs of biotin, 4-biotinamido-2,2,6,6-tetramethyl-1-piperidinyloxy (IV), 3-biotinamido-2,2,5,5-tetramethyl-1-pyrrolidinyloxy (V), 3-biotinamidomethyl-2,2,5,5-tetramethyl-1-pyrrolidinyloxy (VI), and 4-(biotinylglycyl)amino-2,2,6,6-tetramethyl-1-piperidinyloxy (VII), all interacted with avidin, a specific biotin binding protein found in raw egg white, at the same sites as did biotin itself. An unsymmetrical decamethonium spin label (XVIII) in which one of the quaternary methyl groups had been replaced by the 4-(2,2,6,6-tetramethyl-1-piperidinyloxy) moiety was 13 times more potent as an inhibitor of Torpedo californica acetylcholinesterase than the parent drug. The symmetrical decamethonium (XVI) and hexamethonium (XIV) spin labels were 18 and 1.8 times as active as decamethonium in the same assay system. The substitution of the 4-(2,2,6,6-tetramethyl-1-piperidinyloxy) group for the isopropyl groups of beta-adrenergic blocking drugs dichlorisoproterenol and propranolol, to give spin labels XXI and XXII, caused a 45 and 54% reduction, respectively, in the ability of these compounds to inhibit the isoproterenol-stimulated activity of rat fat cell membranes. Finally, modification of primaquine by the introduction of the 4-(2,2,6,6-tetramethyl-1-piperidinyloxy) substituent into the amino group of the butyl side chain completely abolished the ability of the drug to bind to nuclei acids. These results suggest that the incorporation of the nitroxide group into drug molecules may be a useful approach to the synthesis of more specific spin labels for biological systems, such as egg white avidin, acetylcholinesterase, and the beta-adrenergic receptor."}
{"id": "PMID:239238", "title": "Adrenergic agents. 3. Synthesis and adrenergic activity of some catecholamine analogs bearing a substituted sulfonyl or sulfonylalkyl group in the meta position.", "content": "The m-phenolic group of catecholamine beta-adrenergic agonists may be replaced by various functionalities capable of undergoing H bonding. Considerable latitude in the nature of the OH simulating group is permissible with retention of activity; however, the most extensively studied analogs are ones in which a mobile proton is attached to an O or N atom. In a search for new selective bronchodilators a series of catecholamine analogs bearing a substituted sulfonyl or sulfonylalkyl group in the meta position (i.e., groups in which the mobile H is attached to a C atom) was examined. These compounds were studied for beta-adrenergic agonist activity in vitro by measuring their ability to relax tracheal smooth muscle and to increase the rate of spontaneously beating right atria of guinea pigs. Adrenergic activity was influenced by the nature of the alkylene bridge between the sulfonyl and aromatic groups, branching of the ethanolamine side chain, stereochemistry, and substitution of the sulfonyl and amino groups. Beta-adrenergic blockage was noted for some compounds having the sulfonyl attached directly to the ring. Greatest beta-adrenergic agonist potency and tissue selectivity was observed with a m-MeSO2CH2 substituent. One of these compounds, alpha-[[(1,1-dimethylethyl)amino]methyl]-4-hydroxy-3-[(methylsulfonyl)methyl]benzenemethanol hydrochloride (sulfonterol hydrochloride, USAN), was studied more extensively in animals and is presently being examined for bronchodilator activity in man.", "contents": "Adrenergic agents. 3. Synthesis and adrenergic activity of some catecholamine analogs bearing a substituted sulfonyl or sulfonylalkyl group in the meta position. The m-phenolic group of catecholamine beta-adrenergic agonists may be replaced by various functionalities capable of undergoing H bonding. Considerable latitude in the nature of the OH simulating group is permissible with retention of activity; however, the most extensively studied analogs are ones in which a mobile proton is attached to an O or N atom. In a search for new selective bronchodilators a series of catecholamine analogs bearing a substituted sulfonyl or sulfonylalkyl group in the meta position (i.e., groups in which the mobile H is attached to a C atom) was examined. These compounds were studied for beta-adrenergic agonist activity in vitro by measuring their ability to relax tracheal smooth muscle and to increase the rate of spontaneously beating right atria of guinea pigs. Adrenergic activity was influenced by the nature of the alkylene bridge between the sulfonyl and aromatic groups, branching of the ethanolamine side chain, stereochemistry, and substitution of the sulfonyl and amino groups. Beta-adrenergic blockage was noted for some compounds having the sulfonyl attached directly to the ring. Greatest beta-adrenergic agonist potency and tissue selectivity was observed with a m-MeSO2CH2 substituent. One of these compounds, alpha-[[(1,1-dimethylethyl)amino]methyl]-4-hydroxy-3-[(methylsulfonyl)methyl]benzenemethanol hydrochloride (sulfonterol hydrochloride, USAN), was studied more extensively in animals and is presently being examined for bronchodilator activity in man."}
{"id": "PMID:239251", "title": "The use of fresh blood in the treatment of critically injured patients.", "content": "Initial transfusion needs aremet by type-specific rather than low titer O-negative blood. When the patient's problem approaches the magnitude of exchange transfusion (5 to 10 units) in less than 4 hours, platelet transfusion to treat dilutional thrombocytopenia is administered. Fresh frozen plasma is administered to provide clotting factors. When five units have been exceeded, platelet, pro-thrombin, and partial thromboplastin are measured. A blood clot is checked for clotting, retraction, and lysis. These tests screen platelet quantity and the intrinsic and extrinsic clotting system. Administered blood is warmed in a water bath or heating coil. Blood gas analysis (pH, pO2, and pCO2) is performed every five units to allow for precise administration of bicarbonate. The electrocardiogram is used to monitor potassium and calcium abnormalities. Hyperkalemia is seldom a problem. Hypocalcemia may be present transiently and is treated with calcium choride. Component therapy is the standard recommended practice. Fresh blood is recommended for the patient who has had an acute exchange transfusion and continues to require large quantities of blood. Fresh blood obviates the need for combining components and allows one transfusion unit to address itself to the multiple needs of the patient.", "contents": "The use of fresh blood in the treatment of critically injured patients. Initial transfusion needs aremet by type-specific rather than low titer O-negative blood. When the patient's problem approaches the magnitude of exchange transfusion (5 to 10 units) in less than 4 hours, platelet transfusion to treat dilutional thrombocytopenia is administered. Fresh frozen plasma is administered to provide clotting factors. When five units have been exceeded, platelet, pro-thrombin, and partial thromboplastin are measured. A blood clot is checked for clotting, retraction, and lysis. These tests screen platelet quantity and the intrinsic and extrinsic clotting system. Administered blood is warmed in a water bath or heating coil. Blood gas analysis (pH, pO2, and pCO2) is performed every five units to allow for precise administration of bicarbonate. The electrocardiogram is used to monitor potassium and calcium abnormalities. Hyperkalemia is seldom a problem. Hypocalcemia may be present transiently and is treated with calcium choride. Component therapy is the standard recommended practice. Fresh blood is recommended for the patient who has had an acute exchange transfusion and continues to require large quantities of blood. Fresh blood obviates the need for combining components and allows one transfusion unit to address itself to the multiple needs of the patient."}
{"id": "PMID:239253", "title": "Spontaneous rupture of the kidney secondary to polyarteritis nodosa.", "content": "Spontaneous rupture of the kidney occurs rarely. Among the known causes polyarteritis nodosa is uncommon with less than 50 cases reported. Diagnosis is difficult to make with certainty. Our case concerns a 38-year-old man whose symptoms originally simulated acute renal colic. Nephrectomy was done. A brief review of the pertinent literature, diagnosis and management is presented.", "contents": "Spontaneous rupture of the kidney secondary to polyarteritis nodosa. Spontaneous rupture of the kidney occurs rarely. Among the known causes polyarteritis nodosa is uncommon with less than 50 cases reported. Diagnosis is difficult to make with certainty. Our case concerns a 38-year-old man whose symptoms originally simulated acute renal colic. Nephrectomy was done. A brief review of the pertinent literature, diagnosis and management is presented."}
{"id": "PMID:239254", "title": "The digestive tract of the whiteback griffon vulture and its role in disease transmission among wild ungulates.", "content": "The digestive tract of the whiteback vulture (Gyps africanus) is described. Some disease organisms were fed to a captive bird to discover if they could survive passage through the tract, and the role of these scavenging birds in the spread of diseases among wild ungulates is discussed.", "contents": "The digestive tract of the whiteback griffon vulture and its role in disease transmission among wild ungulates. The digestive tract of the whiteback vulture (Gyps africanus) is described. Some disease organisms were fed to a captive bird to discover if they could survive passage through the tract, and the role of these scavenging birds in the spread of diseases among wild ungulates is discussed."}
{"id": "PMID:239255", "title": "Chronic shedding tularemia nephritis in rodents: possible relation to occurrence of Francisella tularensis in lotic waters.", "content": "Contamination of streams by Francisella tularensis, a fastidious pathogen, was discovered by Miller in Russia. Subsequently that contamination was found to be the source of extensive human outbreaks, and to occur as well in North America. Circumstantial evidence supports a hypothesis that infected voles are responsible for the contamination, but when freshly isolated F. tularensis palaearctica is inoculated parenterally, only acute illness and death result whereas long-term contamination of streams would seem to demand a more chronic process. Laboratory studies have demonstrated that voles have an apparent predilection to tularemic nephritis when partially immunized before parenteral infection, but also when naive voles are infected orally. Associated chronic bacteriuria would seem to fulfill requirements for protracted contamination of watersheds.", "contents": "Chronic shedding tularemia nephritis in rodents: possible relation to occurrence of Francisella tularensis in lotic waters. Contamination of streams by Francisella tularensis, a fastidious pathogen, was discovered by Miller in Russia. Subsequently that contamination was found to be the source of extensive human outbreaks, and to occur as well in North America. Circumstantial evidence supports a hypothesis that infected voles are responsible for the contamination, but when freshly isolated F. tularensis palaearctica is inoculated parenterally, only acute illness and death result whereas long-term contamination of streams would seem to demand a more chronic process. Laboratory studies have demonstrated that voles have an apparent predilection to tularemic nephritis when partially immunized before parenteral infection, but also when naive voles are infected orally. Associated chronic bacteriuria would seem to fulfill requirements for protracted contamination of watersheds."}
{"id": "PMID:239258", "title": "The diagnostic value of sputum culture in acute pneumonia.", "content": "In a prospective study of patients with acute pneumonia, the results of bacteriologic analysis of sputum, transtracheal aspirate (TA), and bronchial aspirate (BA) were compared. Streptococcus pneumoniae was grown from all three sources as the predominant organism in 13 of 16 cases; the remaining three patients had nonbacterial lung disease. These data support the traditional concept that culture of the sputum is highly reliable in providing a correct diagnosis in acute pneumonia.", "contents": "The diagnostic value of sputum culture in acute pneumonia. In a prospective study of patients with acute pneumonia, the results of bacteriologic analysis of sputum, transtracheal aspirate (TA), and bronchial aspirate (BA) were compared. Streptococcus pneumoniae was grown from all three sources as the predominant organism in 13 of 16 cases; the remaining three patients had nonbacterial lung disease. These data support the traditional concept that culture of the sputum is highly reliable in providing a correct diagnosis in acute pneumonia."}
{"id": "PMID:239260", "title": "Biochemical evaluation of sympathetic nerve tone in essential hypertension.", "content": "The concentration of plasma catecholamines (CA), serum dopamine beta-hydoxylase (DBH) activity and plasma renin activity (PRA) were simultaneously measured in 55 patients with essential hypertension (EH). Further the enzyme activities of CA biosynthesis in human vas deferens excised at elective vasectomy were related with the blood pressure, plasma CA, serum DBH of 57 men at the time of vasectomy. Total plasma CA and norepinephrine (NE) were increased in 28 and 35% of patients with benign EH, respectively. Total plasma CA were also increased in 45% of men with elevated blood pressure prior to vasectomy. Total plasma CA were correlated with diastolic blood pressure in EH (p less than 0.01). Further, in men with normal and raised blood pressure prior to vasectomy, there was a significant correlation of total plasma CA with systolic and diastolic blood pressure (p less than 0.01). Total plasma CA were correlated with PRA in patients with EH (r=0.497, p less than 0.001). Capacity for NE biosynthesis, vas deferens tyrosine hydroxylase (TYH) activity and dopa decarboxylase (DDC) activity were increased in men with raised blood pressure. There was a direct correlation of total plasma CA with the activities of TYH and DDC (r=0.46, and 0.54, p less than 0.005). Increased sympathetic nerve tonicity associated with increased neurotransmitter biosynthesis may be an important factor responsible for blood pressure elevation in men prior to vasectomy and in others with EH. The some patients with EH may have a renin-catecholamine relationship and both pressor systems may be linked to be a pathogenic factor for the elevation of blood pressure.", "contents": "Biochemical evaluation of sympathetic nerve tone in essential hypertension. The concentration of plasma catecholamines (CA), serum dopamine beta-hydoxylase (DBH) activity and plasma renin activity (PRA) were simultaneously measured in 55 patients with essential hypertension (EH). Further the enzyme activities of CA biosynthesis in human vas deferens excised at elective vasectomy were related with the blood pressure, plasma CA, serum DBH of 57 men at the time of vasectomy. Total plasma CA and norepinephrine (NE) were increased in 28 and 35% of patients with benign EH, respectively. Total plasma CA were also increased in 45% of men with elevated blood pressure prior to vasectomy. Total plasma CA were correlated with diastolic blood pressure in EH (p less than 0.01). Further, in men with normal and raised blood pressure prior to vasectomy, there was a significant correlation of total plasma CA with systolic and diastolic blood pressure (p less than 0.01). Total plasma CA were correlated with PRA in patients with EH (r=0.497, p less than 0.001). Capacity for NE biosynthesis, vas deferens tyrosine hydroxylase (TYH) activity and dopa decarboxylase (DDC) activity were increased in men with raised blood pressure. There was a direct correlation of total plasma CA with the activities of TYH and DDC (r=0.46, and 0.54, p less than 0.005). Increased sympathetic nerve tonicity associated with increased neurotransmitter biosynthesis may be an important factor responsible for blood pressure elevation in men prior to vasectomy and in others with EH. The some patients with EH may have a renin-catecholamine relationship and both pressor systems may be linked to be a pathogenic factor for the elevation of blood pressure."}
{"id": "PMID:239263", "title": "[Clinical effects of lividomycin on respiratory tract infections, primarily wet cases of bronchiectasis (author's transl)].", "content": "Patients with various respiratory infections, primarily wet cases of bronchiectasis, were treated with lividomycin (LVDM)  at a dose of 1 g/day for about a week. The results obtained are as follows: 1. Of the 15 patients with refractory bronchiectasis who had previously been treated with various other antibiotics, 11 patients (73.3%) responded to LVDM. Although there was no patient who responded to LVDM excellently, good cures were achieved in 5 pateints and fair cures in 6 patients. 2. In bronchiectasis patients having infections in association with pulmonary tuberculosis (mixed infections), LVDM did not show any remarkable effects, excepting that fair cures were achieved in 3 patients. 3. In the 7 patients with acute bronchopneumonia, excellent, good and fair cures were achieved in 1, 5 and 1 patient, respectively. Although LVDM was effective in all of the patients with the said infection, the number of the patients responded excellently was meager and the onset of action seemed to be somewhat slow. 4. In one patient with lobar pneumonia, LVDM was not effective. 5. The MIC values of LVDM for clinically isolated various organisms are summarized below: Pseudomonas aeruginosa 50 mcg/ml, Klebsiella pneumoniae 3.13 to 6.25 mcg/ml, Haemophilis influenzae 1.56 to 6.25 mcg/ml, Diplococcus pneumoniae 50 mcg/ml, alpha-Streptococcus 50 to 100 mcg/ml, beta-Streptococcus 100 mcg/ml, and Staphylococcus aureus 1.56 mcg/ml. 6. In spite of the fact that a majority of the patients participated in this study were the aged, LVDM's side effects were limited to an increase of BUN (one patient) and eruption (one patient). Any noticeable changes in hepatic and renal function, hearing acuity, etc. were not observed. As indicated above, LVDM was effective against, respiratory infections as well as infections of the urinary tract on which a considerable number of research has already been reported. Thus, it is considered to be worthwhile to use LVDM for the treatment of respiratory infections.", "contents": "[Clinical effects of lividomycin on respiratory tract infections, primarily wet cases of bronchiectasis (author's transl)]. Patients with various respiratory infections, primarily wet cases of bronchiectasis, were treated with lividomycin (LVDM)  at a dose of 1 g/day for about a week. The results obtained are as follows: 1. Of the 15 patients with refractory bronchiectasis who had previously been treated with various other antibiotics, 11 patients (73.3%) responded to LVDM. Although there was no patient who responded to LVDM excellently, good cures were achieved in 5 pateints and fair cures in 6 patients. 2. In bronchiectasis patients having infections in association with pulmonary tuberculosis (mixed infections), LVDM did not show any remarkable effects, excepting that fair cures were achieved in 3 patients. 3. In the 7 patients with acute bronchopneumonia, excellent, good and fair cures were achieved in 1, 5 and 1 patient, respectively. Although LVDM was effective in all of the patients with the said infection, the number of the patients responded excellently was meager and the onset of action seemed to be somewhat slow. 4. In one patient with lobar pneumonia, LVDM was not effective. 5. The MIC values of LVDM for clinically isolated various organisms are summarized below: Pseudomonas aeruginosa 50 mcg/ml, Klebsiella pneumoniae 3.13 to 6.25 mcg/ml, Haemophilis influenzae 1.56 to 6.25 mcg/ml, Diplococcus pneumoniae 50 mcg/ml, alpha-Streptococcus 50 to 100 mcg/ml, beta-Streptococcus 100 mcg/ml, and Staphylococcus aureus 1.56 mcg/ml. 6. In spite of the fact that a majority of the patients participated in this study were the aged, LVDM's side effects were limited to an increase of BUN (one patient) and eruption (one patient). Any noticeable changes in hepatic and renal function, hearing acuity, etc. were not observed. As indicated above, LVDM was effective against, respiratory infections as well as infections of the urinary tract on which a considerable number of research has already been reported. Thus, it is considered to be worthwhile to use LVDM for the treatment of respiratory infections."}
{"id": "PMID:239265", "title": "Effects of prostaglandin E2 on the electrical property of the pregnant mouse myometrium.", "content": "At any stage of gestation, low concentrations of PGE2 increased that frequency and number of spikes in a train discharge without any marked change of the membrane potential. An increased concentration depolarized the membrane and produced continuous spike generation. A further increase in concentration of PGE2 produced a depolarization block of spike generation. The sensitivity of the myometrium to PGE2 was markedly increased during the progress of gestation so that at the late stage of gestation, the sensitivity was more than 100 times greater than at the early stage. The longitudinal muscle showed a higher sensitivity to PGE2 than the circular muscle. However, both muscles showed a similar sensitivity to oxytocin. In the longitudinal muscle, desensitization to PGE2 occurred more quickly than to oxytocin. When PGE2 produced a slight depolarization of the membrane, the membrane resistance was increased. However, when the membrane potential was displaced to the control level by applying a hyperpolarizing current, the membrane resistance was slightly reduced. Displacement of the membrane potential to the level before drug application restored spike generation. However, the membrane resistance was still reduced. In Na-deficient Locke solution or in Ca-free Mg-Locke solution, the depolarization induced by PGE2 was suppressed but not suppressed by, in K-deficient Locke solution.", "contents": "Effects of prostaglandin E2 on the electrical property of the pregnant mouse myometrium. At any stage of gestation, low concentrations of PGE2 increased that frequency and number of spikes in a train discharge without any marked change of the membrane potential. An increased concentration depolarized the membrane and produced continuous spike generation. A further increase in concentration of PGE2 produced a depolarization block of spike generation. The sensitivity of the myometrium to PGE2 was markedly increased during the progress of gestation so that at the late stage of gestation, the sensitivity was more than 100 times greater than at the early stage. The longitudinal muscle showed a higher sensitivity to PGE2 than the circular muscle. However, both muscles showed a similar sensitivity to oxytocin. In the longitudinal muscle, desensitization to PGE2 occurred more quickly than to oxytocin. When PGE2 produced a slight depolarization of the membrane, the membrane resistance was increased. However, when the membrane potential was displaced to the control level by applying a hyperpolarizing current, the membrane resistance was slightly reduced. Displacement of the membrane potential to the level before drug application restored spike generation. However, the membrane resistance was still reduced. In Na-deficient Locke solution or in Ca-free Mg-Locke solution, the depolarization induced by PGE2 was suppressed but not suppressed by, in K-deficient Locke solution."}
{"id": "PMID:239266", "title": "An intermediate in the photolytic process of extracted squid rhodopsin.", "content": "To clarify the formation process of acid metarhodopsin in the cephalopod rhodopsin cycle, changes in the difference spectrum of squid (Todarodes pacificus) rhodopsin in acid (pH 5.7, or pH 6.1) and alkaline (pH 10.2) solutions were studied at various temperatures by applying the flash photolytic technique. An intermediate with an absorption maximum at about 475 nm was transformed from lumirhodopsin prior to the formation of acid metarhodopsin independently of the pH of the solution. In alkaline solution, some of the converted acid metarhodopsins were then transformed to alkaline metarhodopsins. The conversion of lumirhodopsin to acid metarhodopsin seemed to be a first-order chain reaction.", "contents": "An intermediate in the photolytic process of extracted squid rhodopsin. To clarify the formation process of acid metarhodopsin in the cephalopod rhodopsin cycle, changes in the difference spectrum of squid (Todarodes pacificus) rhodopsin in acid (pH 5.7, or pH 6.1) and alkaline (pH 10.2) solutions were studied at various temperatures by applying the flash photolytic technique. An intermediate with an absorption maximum at about 475 nm was transformed from lumirhodopsin prior to the formation of acid metarhodopsin independently of the pH of the solution. In alkaline solution, some of the converted acid metarhodopsins were then transformed to alkaline metarhodopsins. The conversion of lumirhodopsin to acid metarhodopsin seemed to be a first-order chain reaction."}
{"id": "PMID:239267", "title": "Effects of beta-adrenergic receptor blocking agents on blood pressure in conscious hypertensive rats.", "content": "The effects of beta-adrenergic receptor blocking agents administered i.v. on the blood pressure in conscious spontaneously hypertensive rats (SHR), renal hypertensive rats (RHR) and normotensive Wistar strain rats (NR) were studied. dl-Propranolol and dl-YB-2, 1 mg/kg i.v., caused a sustained rise in blood pressure in SHR and RHR. The maximum response of each beta-blocking agent after phentolamine, 10 mg/kg i.v., in SHR and RHR was significantly larger than that in NR. The potency ratio for the hypertensive activities of the 1- and d-isomers of propranolol and YB-2 was similar to the ratio of their beta-blocking activities. The pressor effects of the beta-blocking agents after phentolamine were significantly inhibited by adrenalectomy, reserpinization and pretreatment with hexamethonium. The results suggest that the pressor effect of the beta-blocking agents may be due to their beta-blocking activities and the unmasking of alpha-receptor activities of the blood vessels. Furthermore, the greater pressor effect of the agents observed in hypertensive rats is attributed to a greater activity of the sympathetic nervous system in these rats as compared to normotensive rats.", "contents": "Effects of beta-adrenergic receptor blocking agents on blood pressure in conscious hypertensive rats. The effects of beta-adrenergic receptor blocking agents administered i.v. on the blood pressure in conscious spontaneously hypertensive rats (SHR), renal hypertensive rats (RHR) and normotensive Wistar strain rats (NR) were studied. dl-Propranolol and dl-YB-2, 1 mg/kg i.v., caused a sustained rise in blood pressure in SHR and RHR. The maximum response of each beta-blocking agent after phentolamine, 10 mg/kg i.v., in SHR and RHR was significantly larger than that in NR. The potency ratio for the hypertensive activities of the 1- and d-isomers of propranolol and YB-2 was similar to the ratio of their beta-blocking activities. The pressor effects of the beta-blocking agents after phentolamine were significantly inhibited by adrenalectomy, reserpinization and pretreatment with hexamethonium. The results suggest that the pressor effect of the beta-blocking agents may be due to their beta-blocking activities and the unmasking of alpha-receptor activities of the blood vessels. Furthermore, the greater pressor effect of the agents observed in hypertensive rats is attributed to a greater activity of the sympathetic nervous system in these rats as compared to normotensive rats."}
{"id": "PMID:239269", "title": "[Electric counter shock therapy as a rehabilitation stage for patients with surgically treated acquired heart diseases].", "content": "A total of 910 case-reports on electropulse treatment of fibrillation arrhythmia are analyzed in the light of rehabilitating patients operated upon for acquired heart diseases. Experience has shown that re-establishment and retention of the sinus rhythm is of decisive importance in the restitution of physical activity and capacity for work. However, investigations have confirmed that the electropulse therapy helps achieve but good immediate results, whereas the remote ones remain unsatisfactory. The problem of stabilizing the rhythm still awaits its solution. The application of agents blocking the beta-adrenoreceptors has but insignificantly reduced the incidence of recurrent episodes of auricular fibrillation.", "contents": "[Electric counter shock therapy as a rehabilitation stage for patients with surgically treated acquired heart diseases]. A total of 910 case-reports on electropulse treatment of fibrillation arrhythmia are analyzed in the light of rehabilitating patients operated upon for acquired heart diseases. Experience has shown that re-establishment and retention of the sinus rhythm is of decisive importance in the restitution of physical activity and capacity for work. However, investigations have confirmed that the electropulse therapy helps achieve but good immediate results, whereas the remote ones remain unsatisfactory. The problem of stabilizing the rhythm still awaits its solution. The application of agents blocking the beta-adrenoreceptors has but insignificantly reduced the incidence of recurrent episodes of auricular fibrillation."}
{"id": "PMID:239270", "title": "[Some characteristics of the state of the sympatho-adrenal system in various hemodynamic variants of hypertension].", "content": "In 40 patients with umcomplicated hypertension their general haemodynamics was compared with the excretion of catecholamines and their metabolites. On the initial stage of the disease the hormonal link was found to prevail over the mediator one; the decreasing excretion of bound catecholamines after the administration of Isuprel indicates that a disbalance between the secretion and inactivation of catecholamines develops as early as on this stage of the disease. Later, in resistance hypertension the administration if Isuprel resulted in an increased excretion of free noradrenalin, which is interpreted as a sign of increased reactivity of this link; no such reaction is noted in ejection hypertension. A study of all these links of the sympathoadrenal system is important for the understanding of the pathogenesis of hypertension and for the choice of this therapy.", "contents": "[Some characteristics of the state of the sympatho-adrenal system in various hemodynamic variants of hypertension]. In 40 patients with umcomplicated hypertension their general haemodynamics was compared with the excretion of catecholamines and their metabolites. On the initial stage of the disease the hormonal link was found to prevail over the mediator one; the decreasing excretion of bound catecholamines after the administration of Isuprel indicates that a disbalance between the secretion and inactivation of catecholamines develops as early as on this stage of the disease. Later, in resistance hypertension the administration if Isuprel resulted in an increased excretion of free noradrenalin, which is interpreted as a sign of increased reactivity of this link; no such reaction is noted in ejection hypertension. A study of all these links of the sympathoadrenal system is important for the understanding of the pathogenesis of hypertension and for the choice of this therapy."}
{"id": "PMID:239275", "title": "On the physiological functions of teichoic acids.", "content": "The choline-containing teichoic acids of pneumococci can be modified by biosynthetic replacement of the choline residues with certain structural analogues, such as ethanolamine (EA) or the N-monomethyl-(MEA) and N-dimethyl-(DEA) amino derivatives of ethanolamine. Cells containing such analogues in their teichoic acids develop pleiomorphic alterations in several physiological properties, which include resistance to detergent-induced lysis and inhibition of cell separation (chain formation). We report here the results of physiological studies on the mechanism of these two phenomena. Our results are summarized in the following: (a) Pneumococci grown on various amino alcohols produce cell walls of identical amino sugar and amino acid composition. (b) Both choline- and EA-containing teichoic acids seem to follow the same conservative pattern of segregation during growth and cell division.(c)Lysis sensitivity of pneumococci requires the juxtaposition oflysissensitive (choline-containing) cell walls and endogenous autolysin at the cell wall growth zone. (d) Upon readdition of choline to ethanolamine-containing cells, lysis sensitivity and catalytically active (C-type) autolysin reappear in the bacteria with the same kinetics. (e) The chains of EA-grown pneumococci contain fully compartmentalized cells and normal cross walls.", "contents": "On the physiological functions of teichoic acids. The choline-containing teichoic acids of pneumococci can be modified by biosynthetic replacement of the choline residues with certain structural analogues, such as ethanolamine (EA) or the N-monomethyl-(MEA) and N-dimethyl-(DEA) amino derivatives of ethanolamine. Cells containing such analogues in their teichoic acids develop pleiomorphic alterations in several physiological properties, which include resistance to detergent-induced lysis and inhibition of cell separation (chain formation). We report here the results of physiological studies on the mechanism of these two phenomena. Our results are summarized in the following: (a) Pneumococci grown on various amino alcohols produce cell walls of identical amino sugar and amino acid composition. (b) Both choline- and EA-containing teichoic acids seem to follow the same conservative pattern of segregation during growth and cell division.(c)Lysis sensitivity of pneumococci requires the juxtaposition oflysissensitive (choline-containing) cell walls and endogenous autolysin at the cell wall growth zone. (d) Upon readdition of choline to ethanolamine-containing cells, lysis sensitivity and catalytically active (C-type) autolysin reappear in the bacteria with the same kinetics. (e) The chains of EA-grown pneumococci contain fully compartmentalized cells and normal cross walls."}
{"id": "PMID:239276", "title": "Alcoholic head trauma triad.", "content": "An initial description of the alcoholic head trauma triad (fatty liver, acute pneumonia and acute subdural hematoma) is presented. The basic nosological features and pathophysiological interrelationships are discussed and areas for further study delineated.", "contents": "Alcoholic head trauma triad. An initial description of the alcoholic head trauma triad (fatty liver, acute pneumonia and acute subdural hematoma) is presented. The basic nosological features and pathophysiological interrelationships are discussed and areas for further study delineated."}
{"id": "PMID:239277", "title": "Hormonal responses in ethanol-induced hypoglycemia.", "content": "Seven patients with clinical alcoholic hypoglycemia showed suppressed pretreatment plasma insulin levels and raised concentrations of somatotropin, hydrocortisone and pancreatic glucagon. A prolonged intravenous glucose infusion failed to elicit adequate insulin output and marked hyperglycemia supervened.", "contents": "Hormonal responses in ethanol-induced hypoglycemia. Seven patients with clinical alcoholic hypoglycemia showed suppressed pretreatment plasma insulin levels and raised concentrations of somatotropin, hydrocortisone and pancreatic glucagon. A prolonged intravenous glucose infusion failed to elicit adequate insulin output and marked hyperglycemia supervened."}
{"id": "PMID:239278", "title": "Disulfiram implantation in alcoholism treatment. A review.", "content": "The literature pertaining to the use of implanted disulfiram as a therapeutic modality in the treatment of alcoholism is reviewed.", "contents": "Disulfiram implantation in alcoholism treatment. A review. The literature pertaining to the use of implanted disulfiram as a therapeutic modality in the treatment of alcoholism is reviewed."}
{"id": "PMID:239279", "title": "Autonomic functioning in alcoholics. A study of heart rate and skin conductance.", "content": "Heart rate and skin conductance levels and variability were measured in alcoholics and nonalcoholics during a demanding neuropsychological task. Alcoholics without possible brain damage had a more variable heart rate and were more highly aroused. In the alcoholics with possible brain damage a negative correlation between heart rate variability and performance decrement and an inverse relationship between heart rate and skin conductance variability were found.", "contents": "Autonomic functioning in alcoholics. A study of heart rate and skin conductance. Heart rate and skin conductance levels and variability were measured in alcoholics and nonalcoholics during a demanding neuropsychological task. Alcoholics without possible brain damage had a more variable heart rate and were more highly aroused. In the alcoholics with possible brain damage a negative correlation between heart rate variability and performance decrement and an inverse relationship between heart rate and skin conductance variability were found."}
{"id": "PMID:239280", "title": "Plasma alcohol, smoking, hormone concentrations and self-reported aggression. A study in a social-drinking situation.", "content": "Plasma alcohol concentrations and the number of cigarettes smoked by men during social-drinking situations were significantly related to change in testosterone levels. Age, height, plasma alcohol and smoking were related to self-reports of prior assault and verbal aggression. Agression was not related to testosterone concentration.", "contents": "Plasma alcohol, smoking, hormone concentrations and self-reported aggression. A study in a social-drinking situation. Plasma alcohol concentrations and the number of cigarettes smoked by men during social-drinking situations were significantly related to change in testosterone levels. Age, height, plasma alcohol and smoking were related to self-reports of prior assault and verbal aggression. Agression was not related to testosterone concentration."}
{"id": "PMID:239281", "title": "The influence of alcohol and tobacco on the components of choice reaction time.", "content": "In smokers a low dose of alcohol slightly improved decision time on a choice reaction-time task and in combination with tobacco resulted in significant improvement compared with placebo conditions. In nonsmokers decision time deteriorated significantly after a moderate dose of alcohol but not in smokers. The results are attributed to the stimulant action of a smoking dose of nicotine interacting with low levels of alcohol.", "contents": "The influence of alcohol and tobacco on the components of choice reaction time. In smokers a low dose of alcohol slightly improved decision time on a choice reaction-time task and in combination with tobacco resulted in significant improvement compared with placebo conditions. In nonsmokers decision time deteriorated significantly after a moderate dose of alcohol but not in smokers. The results are attributed to the stimulant action of a smoking dose of nicotine interacting with low levels of alcohol."}
{"id": "PMID:239282", "title": "The politics of prohibition on Namoluk Atoll.", "content": "The drinking patterns and the attempt to institute prohibition during 1969-71 on Namoluk Atoll, in the Eastern Caroline Islands, are described. The question of prohibition became a symbol of an intergenerational struggle for political power, which was eventually won by the younger antiprohibitionists.", "contents": "The politics of prohibition on Namoluk Atoll. The drinking patterns and the attempt to institute prohibition during 1969-71 on Namoluk Atoll, in the Eastern Caroline Islands, are described. The question of prohibition became a symbol of an intergenerational struggle for political power, which was eventually won by the younger antiprohibitionists."}
{"id": "PMID:239283", "title": "Sardines and other fried fish. The consumption of alcoholic beverages on a Micronesian island.", "content": "Drinking parties are an integral aspect of life on Etal Island, despite official sanctions against them. The parties help to preserve certain traditional community values and provide an outlet for tension caused by political and social change.", "contents": "Sardines and other fried fish. The consumption of alcoholic beverages on a Micronesian island. Drinking parties are an integral aspect of life on Etal Island, despite official sanctions against them. The parties help to preserve certain traditional community values and provide an outlet for tension caused by political and social change."}
{"id": "PMID:239284", "title": "Physicians and alcoholics. Factors affecting attitudes of family-practice residents toward alcoholics.", "content": "Family-practice residents rated alcoholics as weaker, sicker and more hopeless and aimless than average persons on an adjective semantic differential, and diabetics as sicker than average persons. The implications for the diagnosis and treatment of alcoholism are discussed.", "contents": "Physicians and alcoholics. Factors affecting attitudes of family-practice residents toward alcoholics. Family-practice residents rated alcoholics as weaker, sicker and more hopeless and aimless than average persons on an adjective semantic differential, and diabetics as sicker than average persons. The implications for the diagnosis and treatment of alcoholism are discussed."}
{"id": "PMID:239285", "title": "Determinants of marital happiness and unhappiness rated by alcoholics and their wives.", "content": "Alcoholic husbands and their wives generally agreed that the major aspects of marital happiness dealt with the quality of interpersonal relations. \"Undesirable vices (excessive gambling, drinking, etc.)\" ranked first as contributing to marital unhappiness while their absence was ranked 27.5 by the husbands and 9.5 by the wives as contributing to marital happiness. The elimination of undesirable habits may resolve much marital misery but it does not necessarily follow that as unhappiness decreases happiness will increase.", "contents": "Determinants of marital happiness and unhappiness rated by alcoholics and their wives. Alcoholic husbands and their wives generally agreed that the major aspects of marital happiness dealt with the quality of interpersonal relations. \"Undesirable vices (excessive gambling, drinking, etc.)\" ranked first as contributing to marital unhappiness while their absence was ranked 27.5 by the husbands and 9.5 by the wives as contributing to marital happiness. The elimination of undesirable habits may resolve much marital misery but it does not necessarily follow that as unhappiness decreases happiness will increase."}
{"id": "PMID:239286", "title": "Application of MMPI alcoholism scales to older alcoholics and problem drinkers.", "content": "The MacAndrew and Holmes alcoholism scales differentiated older domiciled alcoholics and residents with disciplinary problems related to problem drinking from nonalcoholics. It is suggested that the scales can identify older problem drinkers along similar dimensions as alcoholics and that they might be applied to studying problem drinkrs who have as yet not received diagnoses of alcoholism.", "contents": "Application of MMPI alcoholism scales to older alcoholics and problem drinkers. The MacAndrew and Holmes alcoholism scales differentiated older domiciled alcoholics and residents with disciplinary problems related to problem drinking from nonalcoholics. It is suggested that the scales can identify older problem drinkers along similar dimensions as alcoholics and that they might be applied to studying problem drinkrs who have as yet not received diagnoses of alcoholism."}
{"id": "PMID:239287", "title": "Emotionality in offspring of rats fed alcohol while nursing.", "content": "Lactating dams were given liquid diets containing ethanol and their pair-fed controls identical diets with isocaloric sucrose instead of ethanol. The female offspring of mothers given ethanol were more emotionally reactive than were the female offspring of control dams.", "contents": "Emotionality in offspring of rats fed alcohol while nursing. Lactating dams were given liquid diets containing ethanol and their pair-fed controls identical diets with isocaloric sucrose instead of ethanol. The female offspring of mothers given ethanol were more emotionally reactive than were the female offspring of control dams."}
{"id": "PMID:239288", "title": "Patient-treatment interactions among alcoholics.", "content": "The ratins of the different aspects of an alcoholism treatment program by patients before discharge revealed differences in views of the program that were related to differences in personality.", "contents": "Patient-treatment interactions among alcoholics. The ratins of the different aspects of an alcoholism treatment program by patients before discharge revealed differences in views of the program that were related to differences in personality."}
{"id": "PMID:239289", "title": "A further failure to replicate an effect of oral anesthesia on alcohol consumption by rats.", "content": "Oral anesthesia by lidocaine has been reported to increase alcohol consumption in food-restricted rats by a substantial degree. Described herein is a second unsuccessful attempt to replicate the finding.", "contents": "A further failure to replicate an effect of oral anesthesia on alcohol consumption by rats. Oral anesthesia by lidocaine has been reported to increase alcohol consumption in food-restricted rats by a substantial degree. Described herein is a second unsuccessful attempt to replicate the finding."}
{"id": "PMID:239290", "title": "Some correlates of Al-Anon group membership.", "content": "A husband's membership in A.A. was related to greater marital happiness, superior ability as a father and less severe drinking problems.", "contents": "Some correlates of Al-Anon group membership. A husband's membership in A.A. was related to greater marital happiness, superior ability as a father and less severe drinking problems."}
{"id": "PMID:239291", "title": "Revascularization of the right coronary artery by retrograde perfusion of the mammary artery. An experimental study.", "content": "Although the internal mammary artery bypass seems an ideal coronary bypass vessel, it has not usually been possible to use this vessel to bypass distal lesions in the right coronary circulation. In this experiment, the right internal mammary artery was utilized in retrograde fashion to evaluate this anatomically more suitable vessel as a bypass graft to the occluded right coronary artery in the dog. Reversal of acute myocardial ischemia was demonstrated by mapping epicardial ST-segment elevation and measuring surface pH. Preliminary long-term experiments have also demonstrated patency and perfusion of the distal right coronary artery by this method.", "contents": "Revascularization of the right coronary artery by retrograde perfusion of the mammary artery. An experimental study. Although the internal mammary artery bypass seems an ideal coronary bypass vessel, it has not usually been possible to use this vessel to bypass distal lesions in the right coronary circulation. In this experiment, the right internal mammary artery was utilized in retrograde fashion to evaluate this anatomically more suitable vessel as a bypass graft to the occluded right coronary artery in the dog. Reversal of acute myocardial ischemia was demonstrated by mapping epicardial ST-segment elevation and measuring surface pH. Preliminary long-term experiments have also demonstrated patency and perfusion of the distal right coronary artery by this method."}
{"id": "PMID:239292", "title": "Oxygen dissociation after transfusion of blood stored in ACD or CPD solution.", "content": "In 20 patients undergoing open-heart surgery, 2,3-diphosphoglycerate (2,3-DPG) concentrations, oxygen affinity of hemoglobin (Po2 at half saturation of hemoglobin with oxygen [P50]), hemoglobin concentration, and pH were measured repeatedly. Measurements were made before and at various times after open-heart surgery and replacement of blood loss with blood stored in acid-citrate-dextrose (ACD) or citrate-phosphate-dextrose (CPD) solutions for less than 72 hours (10 cases per group). Infusion of ACD blood caused P50 and 2,3-DPG concentration to decrease significantly after the operation. The infusion of blood stored in CPD did not significantly increase the oxygen affinity. No significant changes in hemoglobin concentration or pH were observed immediately after the operation in either group. To compensate for the increased oxygen affinity, there must be a rise in cardiac output or more likely a decrease in venous Po2. The transfusion of CPD blood, therefore, is more favorable in terms of oxygen supply, particularly in patients who have had cardiac surgery.", "contents": "Oxygen dissociation after transfusion of blood stored in ACD or CPD solution. In 20 patients undergoing open-heart surgery, 2,3-diphosphoglycerate (2,3-DPG) concentrations, oxygen affinity of hemoglobin (Po2 at half saturation of hemoglobin with oxygen [P50]), hemoglobin concentration, and pH were measured repeatedly. Measurements were made before and at various times after open-heart surgery and replacement of blood loss with blood stored in acid-citrate-dextrose (ACD) or citrate-phosphate-dextrose (CPD) solutions for less than 72 hours (10 cases per group). Infusion of ACD blood caused P50 and 2,3-DPG concentration to decrease significantly after the operation. The infusion of blood stored in CPD did not significantly increase the oxygen affinity. No significant changes in hemoglobin concentration or pH were observed immediately after the operation in either group. To compensate for the increased oxygen affinity, there must be a rise in cardiac output or more likely a decrease in venous Po2. The transfusion of CPD blood, therefore, is more favorable in terms of oxygen supply, particularly in patients who have had cardiac surgery."}
{"id": "PMID:239293", "title": "The fate of internal mammary arterial implants and bypass conduits for myocardial revascularization. Experimental angiographic, histologic, and ultrastructural observations.", "content": "Experimental angiographic, histologic, and ultrastructural observations were obtained from dogs to determine the fate of internal mammary artery (IMA) implants and aorta-coronary bypass (ACB) conduits in the 3 month postoperative period. Angiographic implant patency and evidence of implants forming collaterals with the coronary circulation did not accurately reflect anatomic luminal narrowing. Subendothelial fibrocellular proliferation similar to that described in saphenous vein grafts occurred with regularity in all IMA implants and ACB conduits. The intimal changes were much more severe in the IMA implants as compared to the ACB conduits: There was 25 to 95 per cent liminal narrowing in the IMA implants, whereas the ACB conduits rarely showed greater than 25 per cent luminal narrowing. Both reduced flow and surgical trauma appeared to be influential determining factors of the intimal proliferative process, whereas devascularization alone seemed less important.", "contents": "The fate of internal mammary arterial implants and bypass conduits for myocardial revascularization. Experimental angiographic, histologic, and ultrastructural observations. Experimental angiographic, histologic, and ultrastructural observations were obtained from dogs to determine the fate of internal mammary artery (IMA) implants and aorta-coronary bypass (ACB) conduits in the 3 month postoperative period. Angiographic implant patency and evidence of implants forming collaterals with the coronary circulation did not accurately reflect anatomic luminal narrowing. Subendothelial fibrocellular proliferation similar to that described in saphenous vein grafts occurred with regularity in all IMA implants and ACB conduits. The intimal changes were much more severe in the IMA implants as compared to the ACB conduits: There was 25 to 95 per cent liminal narrowing in the IMA implants, whereas the ACB conduits rarely showed greater than 25 per cent luminal narrowing. Both reduced flow and surgical trauma appeared to be influential determining factors of the intimal proliferative process, whereas devascularization alone seemed less important."}
{"id": "PMID:239294", "title": "Reversal of pulmonary circulation.", "content": "The preliminary results and the technique of total reversal of the pulmonary circulation (RPC) are presented. Total RPC is technically feasible and not incompatible with life. It affords a new experimental model for in vivo study of pulmonary pathophysiology. The influence of this reversal on blood oxygenation, on pulmonary vascular resistance, and on established pulmonary hypertension, as well as its reaction to hypoxia and acidosis, needs further investigation. RPC may have clinical implications in essential pulmonary hypertension and congenital pulmonary vascular anomalies.", "contents": "Reversal of pulmonary circulation. The preliminary results and the technique of total reversal of the pulmonary circulation (RPC) are presented. Total RPC is technically feasible and not incompatible with life. It affords a new experimental model for in vivo study of pulmonary pathophysiology. The influence of this reversal on blood oxygenation, on pulmonary vascular resistance, and on established pulmonary hypertension, as well as its reaction to hypoxia and acidosis, needs further investigation. RPC may have clinical implications in essential pulmonary hypertension and congenital pulmonary vascular anomalies."}
{"id": "PMID:239295", "title": "The influence of pulsatile perfusion on oxygen uptake by the isolated canine hind limb.", "content": "The possible advantages of pulsatile over continuous blood flow have intrigued cardiac surgeons for years. This issue may have clinical significance for moderate to long cardiopulmonary bypass procedures. In spite of aggressive investigation, this problem remains controversial. A system permitting perfusion of an isolated canine hind limb with constant flow, Pao2, Paco2, oxygen delivery, temperature, and pHa but variable stroke volume was established. Under stable conditions, oxygen uptake by the limb was constant over a wide range of stroke volumes. Regression equations relating oxygen uptake to stroke volume were calculated and found to have a near zero slope. When the hydrogen ion concentration of the blood perfusing tissue is held constant, the oxygen consumption of that tissue is independent of the pulsatile nature of the perfusing blood.", "contents": "The influence of pulsatile perfusion on oxygen uptake by the isolated canine hind limb. The possible advantages of pulsatile over continuous blood flow have intrigued cardiac surgeons for years. This issue may have clinical significance for moderate to long cardiopulmonary bypass procedures. In spite of aggressive investigation, this problem remains controversial. A system permitting perfusion of an isolated canine hind limb with constant flow, Pao2, Paco2, oxygen delivery, temperature, and pHa but variable stroke volume was established. Under stable conditions, oxygen uptake by the limb was constant over a wide range of stroke volumes. Regression equations relating oxygen uptake to stroke volume were calculated and found to have a near zero slope. When the hydrogen ion concentration of the blood perfusing tissue is held constant, the oxygen consumption of that tissue is independent of the pulsatile nature of the perfusing blood."}
{"id": "PMID:239296", "title": "Aorta-coronary bypass grafting with the internal mammary artery: clinical experience in 70 patients.", "content": "Clincal and angiographic results in 70 patients who received free internal mammary artery (IMA) grafts are reviewed. One postoperative death occurred, but it was not related to the free IMA technique. Forty-seven patients underwent postoperative arteriography. The average interval between operation and catheterization was 10.7 months, and the patency rate for 49 free IMA grafts was 89.8 per cent. Of the 29 patients who recieved free IMA grafts as the only revascularization procedure, 21 patients (80 per cent) progressed to Functional Class I and only 5 patients did not have improvement in their functional status.", "contents": "Aorta-coronary bypass grafting with the internal mammary artery: clinical experience in 70 patients. Clincal and angiographic results in 70 patients who received free internal mammary artery (IMA) grafts are reviewed. One postoperative death occurred, but it was not related to the free IMA technique. Forty-seven patients underwent postoperative arteriography. The average interval between operation and catheterization was 10.7 months, and the patency rate for 49 free IMA grafts was 89.8 per cent. Of the 29 patients who recieved free IMA grafts as the only revascularization procedure, 21 patients (80 per cent) progressed to Functional Class I and only 5 patients did not have improvement in their functional status."}
{"id": "PMID:239302", "title": "[The application of interference contrast microscopy in biology (author's transl)].", "content": "Like phase contrast, Nomarski interference contrast microscopy can be used to examine unstained specimens in biology and medicine. The properties of both contrast enhancement techniques are illustrated by various examples. The phase contrast method is especially suited for thin specimens with small differences in refractive index, whereas the interference contrast method supplies good results even of thick specimens. Interference contrast is a valuable supplement to the phase contrast method, and expands the application of microscopy in biology", "contents": "[The application of interference contrast microscopy in biology (author's transl)]. Like phase contrast, Nomarski interference contrast microscopy can be used to examine unstained specimens in biology and medicine. The properties of both contrast enhancement techniques are illustrated by various examples. The phase contrast method is especially suited for thin specimens with small differences in refractive index, whereas the interference contrast method supplies good results even of thick specimens. Interference contrast is a valuable supplement to the phase contrast method, and expands the application of microscopy in biology"}
{"id": "PMID:239305", "title": "ipecacuanha-ipecauanha.", "content": "A survey was conducted among patients attending the casualty department of the Adelaide Children's Hospital to find the length of time which elapsed between the ingestion of a potentially toxic substance and the institution of measures to evacuate the stomach contents. This paper demonstrates that there is often an undue delay before effective treatment is instituted. To overcome this delay, the administration of syrup of ipecacuanha in the home as a first-aid measure in the management of accidental poisoning is advocated.", "contents": "ipecacuanha-ipecauanha. A survey was conducted among patients attending the casualty department of the Adelaide Children's Hospital to find the length of time which elapsed between the ingestion of a potentially toxic substance and the institution of measures to evacuate the stomach contents. This paper demonstrates that there is often an undue delay before effective treatment is instituted. To overcome this delay, the administration of syrup of ipecacuanha in the home as a first-aid measure in the management of accidental poisoning is advocated."}
{"id": "PMID:239307", "title": "Suicide in Brisbane, 1956 to 1973: the drug-death epidemic.", "content": "A study of suicide in Brisbane between the years 1956 and 1973 reveals that there was a sharp rise in the incidence of deaths from barbiturate overdosage, which reached a peak in the mid 1960s. Since then there has been a steady decline in suicide rates from drug overdose and a smaller fall in the rate of other forms of suicide. The decline in the incidence of deaths from carbon monoxide poisoning since 1967 may be due to the use of non-toxic domestic gas. The frequent association between barbiturate suicides and previous ingestion of alcohol indicates the danger of the practice and the probability that many of the victims had major drinking problems. An examination of suicide deaths and the prescribing of barbiturates, benzodiazepines and antidepressant drugs between 1962 and 1973 suggests that the fall in suicide rates was due to the better recognition and treatment of depressive illnesses and to the introduction of the safer benzodiazepines in place of barbiturates. The study indicates that placing restrictions on non-violent methods of suicide does not necessarily result in an increase in suicides from violence.", "contents": "Suicide in Brisbane, 1956 to 1973: the drug-death epidemic. A study of suicide in Brisbane between the years 1956 and 1973 reveals that there was a sharp rise in the incidence of deaths from barbiturate overdosage, which reached a peak in the mid 1960s. Since then there has been a steady decline in suicide rates from drug overdose and a smaller fall in the rate of other forms of suicide. The decline in the incidence of deaths from carbon monoxide poisoning since 1967 may be due to the use of non-toxic domestic gas. The frequent association between barbiturate suicides and previous ingestion of alcohol indicates the danger of the practice and the probability that many of the victims had major drinking problems. An examination of suicide deaths and the prescribing of barbiturates, benzodiazepines and antidepressant drugs between 1962 and 1973 suggests that the fall in suicide rates was due to the better recognition and treatment of depressive illnesses and to the introduction of the safer benzodiazepines in place of barbiturates. The study indicates that placing restrictions on non-violent methods of suicide does not necessarily result in an increase in suicides from violence."}
{"id": "PMID:239310", "title": "[Isoenzymes of alaninarylamidase and gamma-glutamyl-transpeptidase in intrahepatic and extra-hepatic cholostasis (author's transl)].", "content": "In 43 patients with intrahepatic and extrahepatic cholostasis alaninarylamidase (AAP) and gamma-glutamyl-transpeptidase (GGTP) in serum were measured and the isoenzymes were determined in agar-gelectrophoresis. The isoenzyme-fraction 2 (in alpha-2-globulin running) of AAP was significant higher in the group of extra-hepatic cholostasis than in the group of intrahepatic cholostasis. Practical importance of the findings is diminished by large variation coefficients of the results. The importance of isoenzymes of GGTP for differentiation of cholostasis is not large. A special low quotient of two anodic isoenzymes of GGTP (fraction running with alpha-1-globulin  to fraction running with beta-globulin) indicates probably a neoplasm of pancreatobiliary tract if there is a high level of total serum-GGTP.", "contents": "[Isoenzymes of alaninarylamidase and gamma-glutamyl-transpeptidase in intrahepatic and extra-hepatic cholostasis (author's transl)]. In 43 patients with intrahepatic and extrahepatic cholostasis alaninarylamidase (AAP) and gamma-glutamyl-transpeptidase (GGTP) in serum were measured and the isoenzymes were determined in agar-gelectrophoresis. The isoenzyme-fraction 2 (in alpha-2-globulin running) of AAP was significant higher in the group of extra-hepatic cholostasis than in the group of intrahepatic cholostasis. Practical importance of the findings is diminished by large variation coefficients of the results. The importance of isoenzymes of GGTP for differentiation of cholostasis is not large. A special low quotient of two anodic isoenzymes of GGTP (fraction running with alpha-1-globulin  to fraction running with beta-globulin) indicates probably a neoplasm of pancreatobiliary tract if there is a high level of total serum-GGTP."}
{"id": "PMID:239334", "title": "The steady state activity of succinate dehydrogenase in the presence of opposing effectors.II. Reductive activation of succinate dehydrogenase in presence of oxaloacetate.", "content": "The extent of the deactivation of the mitochondrial succinate dehydrogenase by oxaloacetate is a function of the redox state of the enzyme. Oxidized enzyme is deactivated by much lower concentrations of oxaloacetate than those needed to deactivate reduced enzyme. An accurate method for measuring this relationship is the redox titration of the enzymic activity of succinate dehydrogenase, carried out in the presence of oxaloacetate. For each concentration of oxaloacetate a different redox titration curve was reported with the apparent mid-potential decreasing with increasing oxaloacetate. These results are compatible with a model which proposes that both oxidized and reduced enzymes can form the catalytically non-active complex with oxaloacetate, but that the complex formed the the oxidized enzyme is more stable than that formed by the reduced enzyme. When the oxaloacetate concentration is low, reduction of the enzyme will lower the fraction of the succinate dehydrogenase-oxaloacetate complex, a reaction which we observe as reductive activation of the enzyme. If this experiment is repeated in the presence of high concentration of oxaloacetate, no activation of the enzyme takes place, but the low stability of the reduced enzyme oxaloacetate complex is revealed by the rapid exchange of the enzyme-bound oxaloacetate with the free ligand. The rate of this exchange is extremely slow at high positive potential and becomes faster upon lowering of the poise potential. The reductive activation of the succinate dehydrogenase is regarded as a two step reaction. In the first step the reduced non-active complex releases the oxaloacetate and in the second step the active form of the enzyme is evolved. These two steps can be observed experimentally; Reductive activation at a redox potential higher than the mid-potential of the oxaloacetate-malate couple (minus 166 mV) is characterized by Ea = 18 Kca/mole, the final equilibrium level of activation decreases upon lowering of the temperature. Reduction activation of the enzyme at minus 240 mV is a very rapid reaction which goes to completion at all temperatures tested and has an activation energy of 12.5 Kcal/mole. The mechanism of the reductive activation and its possible role in the regulation of succinate dehydrogenase in the mitochondria is discussed.", "contents": "The steady state activity of succinate dehydrogenase in the presence of opposing effectors.II. Reductive activation of succinate dehydrogenase in presence of oxaloacetate. The extent of the deactivation of the mitochondrial succinate dehydrogenase by oxaloacetate is a function of the redox state of the enzyme. Oxidized enzyme is deactivated by much lower concentrations of oxaloacetate than those needed to deactivate reduced enzyme. An accurate method for measuring this relationship is the redox titration of the enzymic activity of succinate dehydrogenase, carried out in the presence of oxaloacetate. For each concentration of oxaloacetate a different redox titration curve was reported with the apparent mid-potential decreasing with increasing oxaloacetate. These results are compatible with a model which proposes that both oxidized and reduced enzymes can form the catalytically non-active complex with oxaloacetate, but that the complex formed the the oxidized enzyme is more stable than that formed by the reduced enzyme. When the oxaloacetate concentration is low, reduction of the enzyme will lower the fraction of the succinate dehydrogenase-oxaloacetate complex, a reaction which we observe as reductive activation of the enzyme. If this experiment is repeated in the presence of high concentration of oxaloacetate, no activation of the enzyme takes place, but the low stability of the reduced enzyme oxaloacetate complex is revealed by the rapid exchange of the enzyme-bound oxaloacetate with the free ligand. The rate of this exchange is extremely slow at high positive potential and becomes faster upon lowering of the poise potential. The reductive activation of the succinate dehydrogenase is regarded as a two step reaction. In the first step the reduced non-active complex releases the oxaloacetate and in the second step the active form of the enzyme is evolved. These two steps can be observed experimentally; Reductive activation at a redox potential higher than the mid-potential of the oxaloacetate-malate couple (minus 166 mV) is characterized by Ea = 18 Kca/mole, the final equilibrium level of activation decreases upon lowering of the temperature. Reduction activation of the enzyme at minus 240 mV is a very rapid reaction which goes to completion at all temperatures tested and has an activation energy of 12.5 Kcal/mole. The mechanism of the reductive activation and its possible role in the regulation of succinate dehydrogenase in the mitochondria is discussed."}
{"id": "PMID:239336", "title": "Vasodilator therapy of idiopathic lactic acidosis.", "content": "Afterload reduction with sodium nitroprusside was performed in a patient with idiopathic lactic acidosis in whom sodium bicarbonate therapy had precipitated pulmonary edema. The drug reduced mean pulmonary-artery wedge pressure from 28 to 12 mm Hg, accompanied by a modest rise in left ventricular stroke work index from 33 to 43 g-m per square meter. Concomitantly, there was dramatic resolution of the metabolic acidemia, the arterial pH rising from 7.19 to 7.61, arterial carbon dioxide tension from 13 to 26 mm Hg, and bicarbonate content from 6 to 28 mEq per liter, and the anion gap falling from 32 to 11 mEq per liter. Metabolic improvement occurred despite a fall in cardiac output from 5.5 to 4.8 liters per minute. These findings support the concept that regional vasoconstriction plays a part in idiopathic lactic acidosis, and suggests that vasodilators may be an effective form of therapy for this almost uniformly fatal disorder.", "contents": "Vasodilator therapy of idiopathic lactic acidosis. Afterload reduction with sodium nitroprusside was performed in a patient with idiopathic lactic acidosis in whom sodium bicarbonate therapy had precipitated pulmonary edema. The drug reduced mean pulmonary-artery wedge pressure from 28 to 12 mm Hg, accompanied by a modest rise in left ventricular stroke work index from 33 to 43 g-m per square meter. Concomitantly, there was dramatic resolution of the metabolic acidemia, the arterial pH rising from 7.19 to 7.61, arterial carbon dioxide tension from 13 to 26 mm Hg, and bicarbonate content from 6 to 28 mEq per liter, and the anion gap falling from 32 to 11 mEq per liter. Metabolic improvement occurred despite a fall in cardiac output from 5.5 to 4.8 liters per minute. These findings support the concept that regional vasoconstriction plays a part in idiopathic lactic acidosis, and suggests that vasodilators may be an effective form of therapy for this almost uniformly fatal disorder."}
{"id": "PMID:239338", "title": "Financial impact of physician assistants on medical practice.", "content": "A study of revenues generated and expenses incurred by 12 physician assistants (MEDEX) who had held salaried positions for at least one year was conducted to determine their financial impact on primary-care practices. Daily charge logs were used to make annual estimates of MEDEX-generated revenues. One method of estimating annual revenues produced a mean of $28,190 per year, and a second method yielded a figure of $30,210 per year. Financial statements were used in two different ways to estimate annual expenses related to the employment of the MEDEX. One procedure indicated average costs of employment were $15,900, and the other $20,100. Ten of the 12 practices in the study experienced substantial gains of estimated revenue over expenses ascribed to the activities of the MEDEX.", "contents": "Financial impact of physician assistants on medical practice. A study of revenues generated and expenses incurred by 12 physician assistants (MEDEX) who had held salaried positions for at least one year was conducted to determine their financial impact on primary-care practices. Daily charge logs were used to make annual estimates of MEDEX-generated revenues. One method of estimating annual revenues produced a mean of $28,190 per year, and a second method yielded a figure of $30,210 per year. Financial statements were used in two different ways to estimate annual expenses related to the employment of the MEDEX. One procedure indicated average costs of employment were $15,900, and the other $20,100. Ten of the 12 practices in the study experienced substantial gains of estimated revenue over expenses ascribed to the activities of the MEDEX."}
{"id": "PMID:239342", "title": "Defect in pyridine nucleotide dependent superoxide production by a particulate fraction from the cranulocytes of patients with chronic granulomatous disease.", "content": "Particulate fractions from normal human granulocytes preactivated with opsonized zymosan were found to catalyze superoxide production in the presence of reduced pyridine nucleotides. Similar preparations from three patients with X-linked chronic granulomatous disease produced no detectable superoxide. The failure to produce superoxide was not due to an inhibitor, since cell-free preparations from the patients' granulocytes had no effect on superoxide production by normal particles. Particles from the mothers of two of the patients produced superoxide at diminished rates; superoxide production by particles from the third mother was normal. These findings suggest that chronic granulomatous disease represents either a defect in a pyridine nucleotide-dependent superoxide-forming oxidase or a lesion in the apparatus responsible for activating the oxidase.", "contents": "Defect in pyridine nucleotide dependent superoxide production by a particulate fraction from the cranulocytes of patients with chronic granulomatous disease. Particulate fractions from normal human granulocytes preactivated with opsonized zymosan were found to catalyze superoxide production in the presence of reduced pyridine nucleotides. Similar preparations from three patients with X-linked chronic granulomatous disease produced no detectable superoxide. The failure to produce superoxide was not due to an inhibitor, since cell-free preparations from the patients' granulocytes had no effect on superoxide production by normal particles. Particles from the mothers of two of the patients produced superoxide at diminished rates; superoxide production by particles from the third mother was normal. These findings suggest that chronic granulomatous disease represents either a defect in a pyridine nucleotide-dependent superoxide-forming oxidase or a lesion in the apparatus responsible for activating the oxidase."}
{"id": "PMID:239343", "title": "A practical chromogenic procedure for the detection of homozygotes and heterozygous carriers of Niemann-Pick disease.", "content": "Niemann-Pick disease is caused by a deficiency of sphingomyelinase in organs and tissues. Determinations of sphingomyelinase activity had required the use of sphingomyelin labeled with radiocarbon or radiohydrogen. These materials are expensive, and their use is restricted to laboratories with radioactive counting facilities. An analogue of sphingomyelin, 2-hexadecanoylamino-4-nitrophenylphosphorylcholine, was synthesized. This substance is hydrolyzed by highly purified sphingomyelinase, and by sphingomyelinease in extracts of human liver tissue, cultured skin fibroblasts, cultured amniotic cells and washed leukocyte preparations. Extracts of tissues and cells from patients with Niemann-Pick disease Type A do not hydrolyze this compound, whereas heterozygotes and patients with Niemann-Pick disease Type C have an intermediate level of hydrolytic activity. Thus, the analogue is a reliable chromogenic reagent for the diagnosis of patients with Niemann-Pick disease and the detection of heterozygous carriers of the Niemann-Pick trait.", "contents": "A practical chromogenic procedure for the detection of homozygotes and heterozygous carriers of Niemann-Pick disease. Niemann-Pick disease is caused by a deficiency of sphingomyelinase in organs and tissues. Determinations of sphingomyelinase activity had required the use of sphingomyelin labeled with radiocarbon or radiohydrogen. These materials are expensive, and their use is restricted to laboratories with radioactive counting facilities. An analogue of sphingomyelin, 2-hexadecanoylamino-4-nitrophenylphosphorylcholine, was synthesized. This substance is hydrolyzed by highly purified sphingomyelinase, and by sphingomyelinease in extracts of human liver tissue, cultured skin fibroblasts, cultured amniotic cells and washed leukocyte preparations. Extracts of tissues and cells from patients with Niemann-Pick disease Type A do not hydrolyze this compound, whereas heterozygotes and patients with Niemann-Pick disease Type C have an intermediate level of hydrolytic activity. Thus, the analogue is a reliable chromogenic reagent for the diagnosis of patients with Niemann-Pick disease and the detection of heterozygous carriers of the Niemann-Pick trait."}
{"id": "PMID:239344", "title": "Prenatal therapy of a patient with vitamin-B12-responsive methylmalonic acidemia.", "content": "Methylmalonic acidemia due to deficient synthesis of 5'-deoxyadenosylcobalamin was discovered in a mid-term fetus by culture of amniotic-fluid cells. Elevated concentrations of methylmalonic acid were also found in amniotic fluid and maternal urine. Treatment during the last nine weeks of gestation with large doses of vitamin B12 given to the mother reversed the increasing maternal excretion of methylmalonic acid, which was 23 mug per milligram of creatinine at 31 weeks' gestation. Just before delivery, the mother was excreting 5 mug, two to three times normal. At birth the methylmalonic acid content of the baby's urine (67 mug per milligram of creatinine) and serum (2.0 mug per milliliter) was only moderately elevated, and serum vitamin B12 concentration was very high. Acid levels rose in serum and urine in response to oral protein loading, but subsided after vitamin B12 administration. The infant is developing normally on a restricted protein diet alone at present. Prenatal therapy of methylmalonic acidemia is possible with large amount of vitamin B12 administered to the mother.", "contents": "Prenatal therapy of a patient with vitamin-B12-responsive methylmalonic acidemia. Methylmalonic acidemia due to deficient synthesis of 5'-deoxyadenosylcobalamin was discovered in a mid-term fetus by culture of amniotic-fluid cells. Elevated concentrations of methylmalonic acid were also found in amniotic fluid and maternal urine. Treatment during the last nine weeks of gestation with large doses of vitamin B12 given to the mother reversed the increasing maternal excretion of methylmalonic acid, which was 23 mug per milligram of creatinine at 31 weeks' gestation. Just before delivery, the mother was excreting 5 mug, two to three times normal. At birth the methylmalonic acid content of the baby's urine (67 mug per milligram of creatinine) and serum (2.0 mug per milliliter) was only moderately elevated, and serum vitamin B12 concentration was very high. Acid levels rose in serum and urine in response to oral protein loading, but subsided after vitamin B12 administration. The infant is developing normally on a restricted protein diet alone at present. Prenatal therapy of methylmalonic acidemia is possible with large amount of vitamin B12 administered to the mother."}
{"id": "PMID:239345", "title": "Decreased serum salicylate concentrations in children with rheumatic fever treated with antacid.", "content": "To determine if the common practice of giving antacids to patients on salicylate therapy has an effect on serum salicylate concentrations, we gave a widely used antacid, aluminum and magnesium hydroxide, and aspirin concomitantly to three children with rheumatic fever.  Urinary pH increased appreciably, and serum salicylate concentrations decreased by 30 to 70 per cent.  In five healthy adult volunteers concomitant administration of antacid had no effect on the bioavailability of aspirin.  Pharmacokinetic analysis revealed that the antacid-induced decrease of serum salicylate concentrations was due to increased renal clearance of salicylate caused by the rise in urinalry pH.", "contents": "Decreased serum salicylate concentrations in children with rheumatic fever treated with antacid. To determine if the common practice of giving antacids to patients on salicylate therapy has an effect on serum salicylate concentrations, we gave a widely used antacid, aluminum and magnesium hydroxide, and aspirin concomitantly to three children with rheumatic fever.  Urinary pH increased appreciably, and serum salicylate concentrations decreased by 30 to 70 per cent.  In five healthy adult volunteers concomitant administration of antacid had no effect on the bioavailability of aspirin.  Pharmacokinetic analysis revealed that the antacid-induced decrease of serum salicylate concentrations was due to increased renal clearance of salicylate caused by the rise in urinalry pH."}
{"id": "PMID:239346", "title": "Inhibition of gastric acid secretion by cimetidine in patients with duodenal ulcer.", "content": "Cimetidine, a non-thiourea-containing H2-receptor antagonist, was studied in seven patients with duodenal ulcer.  Oral doses of 100, 200, and 300 mg were tested.  Each dose significantly inhibited basal and meal-stimulated secretion.  After 300 mg, basal acid secretion was essentially zero for at least five hours.  The meal-stimulated three-hour acid output after the 300-mg dose was reduced by 67%. Cimetidine, 300 mg, decreased meal-stimulated acid secretion significantly more than an optimal effective dose of propantheline bromide (P less than 0.05). Inhibition of meal-stimualted gastric acid secretion showed a significant relation to peak blood cimetidine concentration (r is equal to 0.76, P less than 0.01).  Cimetidine did not affect meal-stimulated gastrin release.  No toxicity was observed after serial doses given during these tests.  Cimetidine may be useful in treatment of acid-peptic diseases provided no important toxicity appears on chronic testing.", "contents": "Inhibition of gastric acid secretion by cimetidine in patients with duodenal ulcer. Cimetidine, a non-thiourea-containing H2-receptor antagonist, was studied in seven patients with duodenal ulcer.  Oral doses of 100, 200, and 300 mg were tested.  Each dose significantly inhibited basal and meal-stimulated secretion.  After 300 mg, basal acid secretion was essentially zero for at least five hours.  The meal-stimulated three-hour acid output after the 300-mg dose was reduced by 67%. Cimetidine, 300 mg, decreased meal-stimulated acid secretion significantly more than an optimal effective dose of propantheline bromide (P less than 0.05). Inhibition of meal-stimualted gastric acid secretion showed a significant relation to peak blood cimetidine concentration (r is equal to 0.76, P less than 0.01).  Cimetidine did not affect meal-stimulated gastrin release.  No toxicity was observed after serial doses given during these tests.  Cimetidine may be useful in treatment of acid-peptic diseases provided no important toxicity appears on chronic testing."}
{"id": "PMID:239347", "title": "Foam-stability test on gastric aspirate and the diagnosis of respiratory-distress syndrome.", "content": "Gastric aspirate, collected from 79 infants within 30 minutes of birth, was subjected to the foam-stability test. The lecithin/sphingomyelin ratio was determined in 27. The results were compared with the incidence of respiratory-distress syndrome as determined independently by different investigators. Of the 59 infants with a positive foam-stability test on gastric aspirate, three had transient respiratory distress, and one the respiratory-distress syndrome; 17 of 22 had lecithin/sphingomyelin ratios greater than 2.0. Of nine infants who had intermediate test results, three were normal, four had transient respiratory distress, and two had the respiratory-distress syndrome. In all the 11 infants with negative foam-stability tests the respiratory-distress syndrome developed. The three gastric aspirates tested in this group had lecithin/sphingomyelin ratios of less than 1.5. These data indicate that the foam-stability test on gastric aspirate is a reliable index of fetal lung maturity in infants whose amniotic fluid is not available.", "contents": "Foam-stability test on gastric aspirate and the diagnosis of respiratory-distress syndrome. Gastric aspirate, collected from 79 infants within 30 minutes of birth, was subjected to the foam-stability test. The lecithin/sphingomyelin ratio was determined in 27. The results were compared with the incidence of respiratory-distress syndrome as determined independently by different investigators. Of the 59 infants with a positive foam-stability test on gastric aspirate, three had transient respiratory distress, and one the respiratory-distress syndrome; 17 of 22 had lecithin/sphingomyelin ratios greater than 2.0. Of nine infants who had intermediate test results, three were normal, four had transient respiratory distress, and two had the respiratory-distress syndrome. In all the 11 infants with negative foam-stability tests the respiratory-distress syndrome developed. The three gastric aspirates tested in this group had lecithin/sphingomyelin ratios of less than 1.5. These data indicate that the foam-stability test on gastric aspirate is a reliable index of fetal lung maturity in infants whose amniotic fluid is not available."}
{"id": "PMID:239349", "title": "Inhibition of growth of Aspergillus flavus and Trichoderma viride by peanut embryos.", "content": "Growth of Aspergillus flavus and Trichoderma viride on agar media was inhibited around embryos of green peanut seeds but not around embryos of cured seeds, intact peanut seeds, or testae. Both fungi were able to colonize intact seeds and testae. Substances inhibitory to A. flavus and T. viride were extracted with acetone from cotyledons of freshly harvested peanut seeds. Four compounds inhibitory to A. flavus were detected in crude acetone extracts. Three of the compounds demonstrated properties of phenolics. Results of this study suggest that inhibitory compounds in peanut cotyledons may play a role in protecting the peanut embryo from fungal infection.", "contents": "Inhibition of growth of Aspergillus flavus and Trichoderma viride by peanut embryos. Growth of Aspergillus flavus and Trichoderma viride on agar media was inhibited around embryos of green peanut seeds but not around embryos of cured seeds, intact peanut seeds, or testae. Both fungi were able to colonize intact seeds and testae. Substances inhibitory to A. flavus and T. viride were extracted with acetone from cotyledons of freshly harvested peanut seeds. Four compounds inhibitory to A. flavus were detected in crude acetone extracts. Three of the compounds demonstrated properties of phenolics. Results of this study suggest that inhibitory compounds in peanut cotyledons may play a role in protecting the peanut embryo from fungal infection."}
{"id": "PMID:239354", "title": "Relations between the effects of histamine, pheniramin and metiamide on spontaneous motility and the formation of cyclic AMP in the isolated rat uterus.", "content": "Histamine (5 X 10(-6) to 10(-3) M) depressed the spontaneous motility of the isolated rat uterus in a dose-dependent manner. Under these conditions uterine cyclic AMP was raised up to 92%. Both effects, uterine relaxation and cyclic AMP accumulation after 2 min could be inhibited dose dependently by the H2-antihistaminic compound metiamide (1.7 X 10(-6) M to 1.7 X 10(-4) M). By contrast, the H1-antagonist pheniramin (4.4 X 10(-5) M) was ineffective. It was concluded that the histamine-induced inhibition of rat uterine motility is mediated by cyclic AMP which is formed in response to stimulation of H2-histaminergic receptors.", "contents": "Relations between the effects of histamine, pheniramin and metiamide on spontaneous motility and the formation of cyclic AMP in the isolated rat uterus. Histamine (5 X 10(-6) to 10(-3) M) depressed the spontaneous motility of the isolated rat uterus in a dose-dependent manner. Under these conditions uterine cyclic AMP was raised up to 92%. Both effects, uterine relaxation and cyclic AMP accumulation after 2 min could be inhibited dose dependently by the H2-antihistaminic compound metiamide (1.7 X 10(-6) M to 1.7 X 10(-4) M). By contrast, the H1-antagonist pheniramin (4.4 X 10(-5) M) was ineffective. It was concluded that the histamine-induced inhibition of rat uterine motility is mediated by cyclic AMP which is formed in response to stimulation of H2-histaminergic receptors."}
{"id": "PMID:239355", "title": "[Influence of pH and calcium of the environment on the electrical activity of an isolated muscle spindle].", "content": "The effects of external pH and Ca concentration were studied as applied to the receptor potential and impulse response of isolated frog muscle spindles. With a decrease in pH the amplitude and duration of the hyperpolarizing phase of the receptor potential increased, and the amplitude of the depolarizing phase decreased. The background firing anc evoked impulse activity decreased. An increase in pH decreased the amplitude and duration of the hyperpolarizing phase of the receptor potential; The background firing initially grew, then decreased up to 30-50 per cent of the standard. An increase in external Ca concentration increased the background firing in an alkaline medium and reduced the firing when pH was neutral or acid. The results are discussed in connection with possible alterations in the rate of the active (electrogenic) and passive transport of the Na and Ca ions", "contents": "[Influence of pH and calcium of the environment on the electrical activity of an isolated muscle spindle]. The effects of external pH and Ca concentration were studied as applied to the receptor potential and impulse response of isolated frog muscle spindles. With a decrease in pH the amplitude and duration of the hyperpolarizing phase of the receptor potential increased, and the amplitude of the depolarizing phase decreased. The background firing anc evoked impulse activity decreased. An increase in pH decreased the amplitude and duration of the hyperpolarizing phase of the receptor potential; The background firing initially grew, then decreased up to 30-50 per cent of the standard. An increase in external Ca concentration increased the background firing in an alkaline medium and reduced the firing when pH was neutral or acid. The results are discussed in connection with possible alterations in the rate of the active (electrogenic) and passive transport of the Na and Ca ions"}
{"id": "PMID:239356", "title": "Fluid removal with negative-pressure hydrostatic ultrafiltration using a partial vacuum.", "content": "Removal of excessive fluid with a negative-pressure hydrostatic ultrafiltration technique using a partial vacuum was performed successfully in eight patients. The technique appears to be a satisfactory means of fluid removal.", "contents": "Fluid removal with negative-pressure hydrostatic ultrafiltration using a partial vacuum. Removal of excessive fluid with a negative-pressure hydrostatic ultrafiltration technique using a partial vacuum was performed successfully in eight patients. The technique appears to be a satisfactory means of fluid removal."}
{"id": "PMID:239357", "title": "Incomplete renal tubular acidosis: some clinical and physiological features.", "content": "17 patients with recurrent calcium-containing renal calculi were studied using the short NH4Cl test and one subject with 'incomplete renal tubular acidosis' was identified. In retrospect the only clue to this diagnosis was a fasting, morning urine pH exceeding 6.0 units. Fasting morning urine pH, which is usually less than 6.0 in subjects who acidify normally, is proposed as a simple screening test for 'incomplete RTA'. Modified high dose NH4Cl tests and Na2SO4 tests were performed in this subject and other patients with either complete or incomplete distal renal tubular acidosis. These studies suggest that the ability to lower urine pH is impaired less with the incomplete than with the complete form of the disease.", "contents": "Incomplete renal tubular acidosis: some clinical and physiological features. 17 patients with recurrent calcium-containing renal calculi were studied using the short NH4Cl test and one subject with 'incomplete renal tubular acidosis' was identified. In retrospect the only clue to this diagnosis was a fasting, morning urine pH exceeding 6.0 units. Fasting morning urine pH, which is usually less than 6.0 in subjects who acidify normally, is proposed as a simple screening test for 'incomplete RTA'. Modified high dose NH4Cl tests and Na2SO4 tests were performed in this subject and other patients with either complete or incomplete distal renal tubular acidosis. These studies suggest that the ability to lower urine pH is impaired less with the incomplete than with the complete form of the disease."}
{"id": "PMID:239358", "title": "Effect of correction of metabolic acidosis on bone mineralisation rates in patients with renal osteomalacia.", "content": "The role of metabolic acidosis in the genesis of renal osteomalacia was investigated by studying bone mineralisation and resorption rates with a combined isotope and balance technique in six patients, before and after the administration of alkali. Correction of blood pH was achieved in five cases and was associated with a significant rise in the bone mineralisation rates and a significant positive trend in the calcium balances. It is suggested that acidosis contributes to the pathogenesis of osteomalacia in renal failure by slowing skeletal mineralisation, possibly by inhibiting bone alkaline phosphatase.", "contents": "Effect of correction of metabolic acidosis on bone mineralisation rates in patients with renal osteomalacia. The role of metabolic acidosis in the genesis of renal osteomalacia was investigated by studying bone mineralisation and resorption rates with a combined isotope and balance technique in six patients, before and after the administration of alkali. Correction of blood pH was achieved in five cases and was associated with a significant rise in the bone mineralisation rates and a significant positive trend in the calcium balances. It is suggested that acidosis contributes to the pathogenesis of osteomalacia in renal failure by slowing skeletal mineralisation, possibly by inhibiting bone alkaline phosphatase."}
{"id": "PMID:239368", "title": "The significance of histamine H1 and H2 receptors on the carotid vascular bed in the dog.", "content": "Intra-arterial histamine produced a dose-dependent increase in common carotid blood flow due to an active vasodilation. A supramaximal dose of mepyramine (H1-blocker) only partially suppressed the effects of lower doses of histamine without influencing those of its higher amounts. Both metiamide and burimamide (H2-blockers) effectively antagonized the mepyramine-resistant carotid vasodilator responses to histamine. The results permit us to conclude that two distinctly different types of histaminergic receptors (H1 and H2) are present in the carotid vascular bed and both of these receptor types are equally important in subserving histamine vasodilation. This fact may explain why, despite incriminating evidence for a pathophysiologic role of histamine, the usual antihistaminic agents are rather ineffective in migrainous headaches. It is suggested that the use of both types of antihistaminic agents concurrently may provide a new approach to the treatment of migrainous headaches, particularly cluster-type headaches.", "contents": "The significance of histamine H1 and H2 receptors on the carotid vascular bed in the dog. Intra-arterial histamine produced a dose-dependent increase in common carotid blood flow due to an active vasodilation. A supramaximal dose of mepyramine (H1-blocker) only partially suppressed the effects of lower doses of histamine without influencing those of its higher amounts. Both metiamide and burimamide (H2-blockers) effectively antagonized the mepyramine-resistant carotid vasodilator responses to histamine. The results permit us to conclude that two distinctly different types of histaminergic receptors (H1 and H2) are present in the carotid vascular bed and both of these receptor types are equally important in subserving histamine vasodilation. This fact may explain why, despite incriminating evidence for a pathophysiologic role of histamine, the usual antihistaminic agents are rather ineffective in migrainous headaches. It is suggested that the use of both types of antihistaminic agents concurrently may provide a new approach to the treatment of migrainous headaches, particularly cluster-type headaches."}
{"id": "PMID:239369", "title": "Gynecologic implications of Burkitt's tumor.", "content": "We have described what we believe to be the first patient with Burkitt's tumor of the ovary to be reported in the gynecological literature. We have also reviewed the remainder of the medical literature in regard to pathology, incidence, epidemiology and clinical characteristics.", "contents": "Gynecologic implications of Burkitt's tumor. We have described what we believe to be the first patient with Burkitt's tumor of the ovary to be reported in the gynecological literature. We have also reviewed the remainder of the medical literature in regard to pathology, incidence, epidemiology and clinical characteristics."}
{"id": "PMID:239371", "title": "Computer assessed fetal heart rate patterns and fetal scalp pH. A preliminary study.", "content": "From the beginning of biophysical and biochemical monitoring of the fetus during labor, a continuing attempt has been made to determine if a reliable correlation exists between these measurements and the well-being of the fetus. If such a correlation did indeed exist, the combined use of the two approaches would permit efficient, relatively simple fetal monitoring. This preliminary report describes the use of computer processed fetal heart rate patterns to predict fetal scalp blood pH. Initial results show a 90% overall accuracy in predictions; when corrected for some of the bias of retrospective predictions, the accuracy is 91% for high pH and 72% for low pH.", "contents": "Computer assessed fetal heart rate patterns and fetal scalp pH. A preliminary study. From the beginning of biophysical and biochemical monitoring of the fetus during labor, a continuing attempt has been made to determine if a reliable correlation exists between these measurements and the well-being of the fetus. If such a correlation did indeed exist, the combined use of the two approaches would permit efficient, relatively simple fetal monitoring. This preliminary report describes the use of computer processed fetal heart rate patterns to predict fetal scalp blood pH. Initial results show a 90% overall accuracy in predictions; when corrected for some of the bias of retrospective predictions, the accuracy is 91% for high pH and 72% for low pH."}
{"id": "PMID:239372", "title": "Maternal and fetal hemodynamic effects of diazoxide.", "content": "Effects of diazoxide on systemic and uterine hemodynamics as well as on fetal circulation and blood respiratory gases were investigated in chronically instrumented pregnant sheep. Diazoxide was administered intravenously either to the ewe or directly to the fetus in doses calculated on the basis of body weight. Transfer of drug across placenta was also investigated. Results showed that: a) when injected into the mother, there was consistent hypotensive effect with increased cardiac output and decreased systemic vascular resistance; uterine blood flow might not change or might decrease slightly with moderate hypotension; when maternal systemic arterial pressure fell to critical closing pressure level, uterine flow decreased significantly; but despite these maternal changes, the fetal circulatory functions were not significantly altered; b) when injected into the fetus in doses up to 15 mg/kg, diazoxide failed to alter fetal circulation appreciably; c) diazoxide crossed the placenta when injected intoeither mother or fetus according to a definite gradient; fetal levels were always lower than maternal levels because of rapid loss of the drug by the fetus; d) moderate maternal and fetal hyperglycemia occurred after drug administration.", "contents": "Maternal and fetal hemodynamic effects of diazoxide. Effects of diazoxide on systemic and uterine hemodynamics as well as on fetal circulation and blood respiratory gases were investigated in chronically instrumented pregnant sheep. Diazoxide was administered intravenously either to the ewe or directly to the fetus in doses calculated on the basis of body weight. Transfer of drug across placenta was also investigated. Results showed that: a) when injected into the mother, there was consistent hypotensive effect with increased cardiac output and decreased systemic vascular resistance; uterine blood flow might not change or might decrease slightly with moderate hypotension; when maternal systemic arterial pressure fell to critical closing pressure level, uterine flow decreased significantly; but despite these maternal changes, the fetal circulatory functions were not significantly altered; b) when injected into the fetus in doses up to 15 mg/kg, diazoxide failed to alter fetal circulation appreciably; c) diazoxide crossed the placenta when injected intoeither mother or fetus according to a definite gradient; fetal levels were always lower than maternal levels because of rapid loss of the drug by the fetus; d) moderate maternal and fetal hyperglycemia occurred after drug administration."}
{"id": "PMID:239374", "title": "Experiments of the origins of optical activity.", "content": "Two recent reports claim that (1) aqueous L-aspartic acid polymerizes faster than D-Asp in the presence of kaolin at 90 degrees, and (2) L-phenylalanine is adsorbed by kaolin more extensively than D-Phe at pH 4(the reverse  being true at pH2). The novelty of these observations and their potential significance for the origin of optical activity has prompted us to duplicate these experiments using more sensitive methods. L- and D, L-Asp in 0.01 M solution were incubated with kaolin at 90 degrees for 8 days. Careful examination of the aqueous residues from such experiments failed to demonstrate any preferential polymerization of L-Asp over D-Asp, or indeed any significant gross polymerization of Asp at all. In other experiments 0.001 M solutions of  D, L-Phe at pH 6 and pH 2 were stirred with large excesses of kaolin for 24 hr, and the aqueous extracts from these mixtures were examined for gross adsorption using the amino acid analyzer. No significant gross adsorption was noted. We then looked for asymmetric adsorption in the aqueous residues using optical rotatory dispersion, gas chromatography and thin layer chromatography. By none of these analytical criteria could we find any evidence whatsoever for the preferential adsorption of D- versus L-Phe from either pH 6 or pH 2 solutions. Finally, in experiments bearing on the origin of optical activity by parity violation during beta-decay, we have irradiated solid samples of D-, L- and D,L-leucine in a 61700 Ci Sr-90 source at Oak Ridge National Lab. for 1.34 yr (total dose: 4.2 x 10(8) rad). Gas chromatographic examination of the (appropriately derivitized) recovered samples showed that the L-Leu was 16.7% decomposed, the D-Leu 11.4% and theD,L-Leu 13.8% decomposed. The recovered D,L-Leu sample had a gas-chromatographically determined enantiomeric composition of 50.8% D-leu and 49.2% L-Leu. These data, though very close to experimental error, may indicate a slight preferential radiolysis of L-Leu compared to D-Leu by the Bremsstrahlung from Sr-90 beta-decay. These high intensity irradiation experiments are being continued on a prolonged basis in order to reach more definitive conclusions.", "contents": "Experiments of the origins of optical activity. Two recent reports claim that (1) aqueous L-aspartic acid polymerizes faster than D-Asp in the presence of kaolin at 90 degrees, and (2) L-phenylalanine is adsorbed by kaolin more extensively than D-Phe at pH 4(the reverse  being true at pH2). The novelty of these observations and their potential significance for the origin of optical activity has prompted us to duplicate these experiments using more sensitive methods. L- and D, L-Asp in 0.01 M solution were incubated with kaolin at 90 degrees for 8 days. Careful examination of the aqueous residues from such experiments failed to demonstrate any preferential polymerization of L-Asp over D-Asp, or indeed any significant gross polymerization of Asp at all. In other experiments 0.001 M solutions of  D, L-Phe at pH 6 and pH 2 were stirred with large excesses of kaolin for 24 hr, and the aqueous extracts from these mixtures were examined for gross adsorption using the amino acid analyzer. No significant gross adsorption was noted. We then looked for asymmetric adsorption in the aqueous residues using optical rotatory dispersion, gas chromatography and thin layer chromatography. By none of these analytical criteria could we find any evidence whatsoever for the preferential adsorption of D- versus L-Phe from either pH 6 or pH 2 solutions. Finally, in experiments bearing on the origin of optical activity by parity violation during beta-decay, we have irradiated solid samples of D-, L- and D,L-leucine in a 61700 Ci Sr-90 source at Oak Ridge National Lab. for 1.34 yr (total dose: 4.2 x 10(8) rad). Gas chromatographic examination of the (appropriately derivitized) recovered samples showed that the L-Leu was 16.7% decomposed, the D-Leu 11.4% and theD,L-Leu 13.8% decomposed. The recovered D,L-Leu sample had a gas-chromatographically determined enantiomeric composition of 50.8% D-leu and 49.2% L-Leu. These data, though very close to experimental error, may indicate a slight preferential radiolysis of L-Leu compared to D-Leu by the Bremsstrahlung from Sr-90 beta-decay. These high intensity irradiation experiments are being continued on a prolonged basis in order to reach more definitive conclusions."}
{"id": "PMID:239378", "title": "[Study of individual variations of the composition of human parotid saliva collected under stimulation].", "content": "Human parotid saliva was studied for its qualitative and quantitative composition; alpha-amylase activity, immunoglobulin A and composition were investigated and showed significant variations from one individual sample to another. The same phenomenon was observed with the inorganic components: CA, P, K, Mg, Na, Cl. The influence of the frequency and length of collection of parotid saliva is discussed.", "contents": "[Study of individual variations of the composition of human parotid saliva collected under stimulation]. Human parotid saliva was studied for its qualitative and quantitative composition; alpha-amylase activity, immunoglobulin A and composition were investigated and showed significant variations from one individual sample to another. The same phenomenon was observed with the inorganic components: CA, P, K, Mg, Na, Cl. The influence of the frequency and length of collection of parotid saliva is discussed."}
{"id": "PMID:239379", "title": "An outbreak of acute hemorrhagic conjunctivitis in Yugoslavia in 1973.", "content": "An outbreak of approximately 200 cases of acute hemorrhagic conjunctivitis is described in Prekmurje, a northern province in Yugoslavia. The epidemic was caused by enterovirus type 70, serologically identical with the causative agents of similar outbreaks in London and Japan. The origin of the outbreak could not be elucidated but a link was seen between this case and a small outbreak in Veenendaal in the Netherlands.", "contents": "An outbreak of acute hemorrhagic conjunctivitis in Yugoslavia in 1973. An outbreak of approximately 200 cases of acute hemorrhagic conjunctivitis is described in Prekmurje, a northern province in Yugoslavia. The epidemic was caused by enterovirus type 70, serologically identical with the causative agents of similar outbreaks in London and Japan. The origin of the outbreak could not be elucidated but a link was seen between this case and a small outbreak in Veenendaal in the Netherlands."}
{"id": "PMID:239375", "title": "Coacervate-like microspheres from lysine-rich proteinoid.", "content": "Microspheres form isothermally from lysine-rich proteinoid when the ionic strength of the solution is increased with NaCl or other salts. Studies with different monovalent anions and with polymers of different amino acid composition indicate that charge neutralization and hydrophobic bonding contribute to microsphere formation. The particles also form in sea water, especially if heated or made slightly alkaline. The microspheres differ from those made from acidic proteinoid but resemble coacervate droplets in some ways (isothermal formation, limited stability, stabilization by quinone, uptake of dyes). Because the constituent lysine-rich proteinoid is of simulated prebiotic origin, the study is interpreted to add emphasis to and suggest an evolutionary continuity for coacervation phenomena.", "contents": "Coacervate-like microspheres from lysine-rich proteinoid. Microspheres form isothermally from lysine-rich proteinoid when the ionic strength of the solution is increased with NaCl or other salts. Studies with different monovalent anions and with polymers of different amino acid composition indicate that charge neutralization and hydrophobic bonding contribute to microsphere formation. The particles also form in sea water, especially if heated or made slightly alkaline. The microspheres differ from those made from acidic proteinoid but resemble coacervate droplets in some ways (isothermal formation, limited stability, stabilization by quinone, uptake of dyes). Because the constituent lysine-rich proteinoid is of simulated prebiotic origin, the study is interpreted to add emphasis to and suggest an evolutionary continuity for coacervation phenomena."}
{"id": "PMID:239373", "title": "Conditions of occurrence for primeval processes of transphosphorylations.", "content": "Model reactions of the phosphate group transfer through hydrolysis-condensation processes without enzymic catalysts are studied in dilute aqueous solutions. Tripolyphosphate and acetylphosphate are used as energy and phosphate donors to perform syntheses of pyrophosphate. Results are discussed in terms of the variation versus pH of the overall standard free enthalpy change.", "contents": "Conditions of occurrence for primeval processes of transphosphorylations. Model reactions of the phosphate group transfer through hydrolysis-condensation processes without enzymic catalysts are studied in dilute aqueous solutions. Tripolyphosphate and acetylphosphate are used as energy and phosphate donors to perform syntheses of pyrophosphate. Results are discussed in terms of the variation versus pH of the overall standard free enthalpy change."}
{"id": "PMID:239376", "title": "Some physical parameters controlling cell size during the evolution of the procaryons.", "content": "Possible factors controlling cell size during the evolution of unicellular organisms have been examined. It has been shown that considerations of osmotic and membrane pressure eqilibria will predict minimal cell sizes which are in good agreement with those found in present day microorganisms. It has also been shown that the possibility of random proton 'noise' would not be a limiting factor for even the smallest organisms or structures. Maximum cell size would be governed by the requirements of diffusion and transport within the cell.", "contents": "Some physical parameters controlling cell size during the evolution of the procaryons. Possible factors controlling cell size during the evolution of unicellular organisms have been examined. It has been shown that considerations of osmotic and membrane pressure eqilibria will predict minimal cell sizes which are in good agreement with those found in present day microorganisms. It has also been shown that the possibility of random proton 'noise' would not be a limiting factor for even the smallest organisms or structures. Maximum cell size would be governed by the requirements of diffusion and transport within the cell."}
{"id": "PMID:239381", "title": "Studies on cystic fibrosis using isoelectric focusing. I. An assay for detection of cystic fibrosis homozygotes and heterozygote carriers from serum.", "content": "We have developed a standardized biophysical assay for the rapid detection of individuals homozygous or heterozygous for cystic fibrosis (C/F). The assay employs isoelectric focusing in thin layer polyacrylamide gels to analyze microliter quantities of whole serum for the presence of a C/F factor protein and for deletions in a group of proteins called proteins B, C, and D (Fig, 1). A pH 5-10 gradient is used (Fig. 2) and each sample is screened using a serum volume which contains 300 micrograms immunoglobulin G (IgG). Individuals homozygous or heterozygous for C/F are distinguished from normal unaffected individuals on the basis of the presence of a C/F factor protein band (Table 1). Heterozygous carriers for C/F are distinguished from C/F homozygotes 75 percent of the time, on the basis of a deletion in either band B, C, or D (Table 2). On the basis of screening 65 patients with cystic fibrosis, 61 heterozygous carriers for C/F, and 105 normal control subjects, it was concluded that no obvious correlation existed between either sex, age, or severity of the disease in the individual C/F patient, and the absolute presence or absence of the C/F factor. In addition, no correlation existed between sex or age and the presence of the C/F factor or deletions in proteins B, C, and D in the individual heterozygous carrier for C/F or normal control subjects. Analysis of serum samples from 68 patients with a variety of other diseases, many with clinical symptoms resembling those seen in the patient with cystic fibrosis (Table 3), indicated that the C/F factor protein described in this study appears to be diagnostic for C/F genotypes, with the possible exception of patients with certain types of leukemia.", "contents": "Studies on cystic fibrosis using isoelectric focusing. I. An assay for detection of cystic fibrosis homozygotes and heterozygote carriers from serum. We have developed a standardized biophysical assay for the rapid detection of individuals homozygous or heterozygous for cystic fibrosis (C/F). The assay employs isoelectric focusing in thin layer polyacrylamide gels to analyze microliter quantities of whole serum for the presence of a C/F factor protein and for deletions in a group of proteins called proteins B, C, and D (Fig, 1). A pH 5-10 gradient is used (Fig. 2) and each sample is screened using a serum volume which contains 300 micrograms immunoglobulin G (IgG). Individuals homozygous or heterozygous for C/F are distinguished from normal unaffected individuals on the basis of the presence of a C/F factor protein band (Table 1). Heterozygous carriers for C/F are distinguished from C/F homozygotes 75 percent of the time, on the basis of a deletion in either band B, C, or D (Table 2). On the basis of screening 65 patients with cystic fibrosis, 61 heterozygous carriers for C/F, and 105 normal control subjects, it was concluded that no obvious correlation existed between either sex, age, or severity of the disease in the individual C/F patient, and the absolute presence or absence of the C/F factor. In addition, no correlation existed between sex or age and the presence of the C/F factor or deletions in proteins B, C, and D in the individual heterozygous carrier for C/F or normal control subjects. Analysis of serum samples from 68 patients with a variety of other diseases, many with clinical symptoms resembling those seen in the patient with cystic fibrosis (Table 3), indicated that the C/F factor protein described in this study appears to be diagnostic for C/F genotypes, with the possible exception of patients with certain types of leukemia."}
{"id": "PMID:239382", "title": "Studies of methylmalonyl coenzyme A carbonylmutase activity in methylmalonic acidemia. I. Correlation of clinical, hepatic, and fibroblast data.", "content": "Methylmalonyl-CoA carbonylmutase (mutase) activity was measured in fibroblast extracts from 15 patients with methylmalonic acidemia and in extracts of postmortem tissues from 6 of these children. Propionate oxidation and synthesis of 5-deoxyadenosylcobalamin (AdoCbl, the vitamin B12 coenzyme that is part of the mutase holoenzyme) were measured in intact fibroblasts. Mutase activity was low in the absence of added AdoCbl in fibroblast extracts from both control subjects and patients. When the assay included supplemental AdoCbl, mutase activity increased in the control subjects (to 24.0 pmol succinate/mg protein/min) and in extracts from eight of the patients (20.8 pmol/mg protein/min), but showed almost no change in extracts from the other seven patients (0.16 pmol/mg protein/min). We have defined the eight fibroblast lines that showed normal mutase activity in the presence of AdoCbl as \"responsive lines\" and the other seven lines as \"nonresponsive.\" In the liver or kidney extracts of postmortem tissues, mutase activity responded to AdoCbl supplementation if fibroblast mutase activity from that patient had responded, and failed to respond if fibroblast activity failed to respond. Mean propionate oxidation in intact fibroblasts was much higher in control lines than in either responsive or nonresponsive lines (0.728 vs 0.097 vs 0.080 nmol CO2/10(6) cells/hr, respectively). AdoCbl synthesis was normal (0.27 pg AdoCbl/mg cells wet weight) in nonresponsive fibroblasts but was undetectable (less than 0.005 pg/mg cells) in the responsive lines. Thus, the deficiency of mutase activity in responsive fibroblast lines is due to the failure to synthesize significant amounts of AdoCbl, whereas the deficiency in nonresponsive lines is due to some other abnormality, presumably a defect in the mutase apoenzyme.", "contents": "Studies of methylmalonyl coenzyme A carbonylmutase activity in methylmalonic acidemia. I. Correlation of clinical, hepatic, and fibroblast data. Methylmalonyl-CoA carbonylmutase (mutase) activity was measured in fibroblast extracts from 15 patients with methylmalonic acidemia and in extracts of postmortem tissues from 6 of these children. Propionate oxidation and synthesis of 5-deoxyadenosylcobalamin (AdoCbl, the vitamin B12 coenzyme that is part of the mutase holoenzyme) were measured in intact fibroblasts. Mutase activity was low in the absence of added AdoCbl in fibroblast extracts from both control subjects and patients. When the assay included supplemental AdoCbl, mutase activity increased in the control subjects (to 24.0 pmol succinate/mg protein/min) and in extracts from eight of the patients (20.8 pmol/mg protein/min), but showed almost no change in extracts from the other seven patients (0.16 pmol/mg protein/min). We have defined the eight fibroblast lines that showed normal mutase activity in the presence of AdoCbl as \"responsive lines\" and the other seven lines as \"nonresponsive.\" In the liver or kidney extracts of postmortem tissues, mutase activity responded to AdoCbl supplementation if fibroblast mutase activity from that patient had responded, and failed to respond if fibroblast activity failed to respond. Mean propionate oxidation in intact fibroblasts was much higher in control lines than in either responsive or nonresponsive lines (0.728 vs 0.097 vs 0.080 nmol CO2/10(6) cells/hr, respectively). AdoCbl synthesis was normal (0.27 pg AdoCbl/mg cells wet weight) in nonresponsive fibroblasts but was undetectable (less than 0.005 pg/mg cells) in the responsive lines. Thus, the deficiency of mutase activity in responsive fibroblast lines is due to the failure to synthesize significant amounts of AdoCbl, whereas the deficiency in nonresponsive lines is due to some other abnormality, presumably a defect in the mutase apoenzyme."}
{"id": "PMID:239384", "title": "Ccomparison of cisternal and lumbar cerebrospinal fluid pH in high altitude natives.", "content": "Samples of cisternal or lumbar cerebrospinal fluid were obtained from 20 young male volunteers born and living at high altitude (3500 to 4800 m). The pH, carbon dioxide and oxygen tensions, and bicarbonate concentration were measured and compared with those in the arterial and jugular venous blood. A consistent difference between the two CSF compartments was noted, particularly a lower pH (0.05), a higher PCO2 (7 Torr), and a lower PO2 (7 Torr) at the lumbar site. Mean bicarbonate concentration was not significantly different at the two sites. The main factor is PCO2, which controls the pH variation. These differences were more marked in high-altitude natives than in man at sea level. The existence of a consistent inhomogeneity of CSF acid-base content emphasizes the inaccuracy of using lumbar CSF pH to estimate the ECF pH as regulator of pulmonary ventilation and determinant of cerebral blood flow.", "contents": "Ccomparison of cisternal and lumbar cerebrospinal fluid pH in high altitude natives. Samples of cisternal or lumbar cerebrospinal fluid were obtained from 20 young male volunteers born and living at high altitude (3500 to 4800 m). The pH, carbon dioxide and oxygen tensions, and bicarbonate concentration were measured and compared with those in the arterial and jugular venous blood. A consistent difference between the two CSF compartments was noted, particularly a lower pH (0.05), a higher PCO2 (7 Torr), and a lower PO2 (7 Torr) at the lumbar site. Mean bicarbonate concentration was not significantly different at the two sites. The main factor is PCO2, which controls the pH variation. These differences were more marked in high-altitude natives than in man at sea level. The existence of a consistent inhomogeneity of CSF acid-base content emphasizes the inaccuracy of using lumbar CSF pH to estimate the ECF pH as regulator of pulmonary ventilation and determinant of cerebral blood flow."}
{"id": "PMID:239385", "title": "Lactic acid permeation rate in working gastrocnemii of dogs during metabolic alkalosis and acidosis.", "content": "In isolated, blood perfused, supramaximally stimulated, isotonically working gastrocnemii of dogs lactic acid (LA) output and O2-consumption (V O2) were measured according to the Fick principle. Simultaneously concentration of muscle tissue was determined at rest and at different times during exercise. In one series of experiments metabolic alkalosis was induced by infusions of THAM of Na bicarbonate. As a result arterial pH increased to about 7.5 and standard [HCO3-1] to 31-35 mmol per 1. In another group of experiments metabolic acidosis was induced by HCl infusions. In these experiments pH decreased to 7.0-7.1 and standard [HO301] to 8-11 mmol per 1. During the first 3-4 min after the onset of exercise LA concentration of muscle tissue rose to 18-19 mumol per g wet weight in both series of experiments. During acidosis the highest average values for LA release from the muscle were about 1.1 mumoles per g per minute. During alkalosis LA permeation rate was nearly three times as high. As a consequence of increased rate of permeation, LA concentration of muscle tissue decreased more rapidly in alkalosis than in acidosis. In both series of experiments work per time and VO2 were practically equal during the first 5-6 min of exercise. Thereafter work per time and VO2 decreased more rapidly in acidosis than in alkalosis, a result which probably is due to higher LA concentration in muscle at this time in acidosis. It is concluded that LA permeation rate across muscle cell membrane is increased by high extracellular HCO3- concentration in combination with low H+ activity and vice versa.", "contents": "Lactic acid permeation rate in working gastrocnemii of dogs during metabolic alkalosis and acidosis. In isolated, blood perfused, supramaximally stimulated, isotonically working gastrocnemii of dogs lactic acid (LA) output and O2-consumption (V O2) were measured according to the Fick principle. Simultaneously concentration of muscle tissue was determined at rest and at different times during exercise. In one series of experiments metabolic alkalosis was induced by infusions of THAM of Na bicarbonate. As a result arterial pH increased to about 7.5 and standard [HCO3-1] to 31-35 mmol per 1. In another group of experiments metabolic acidosis was induced by HCl infusions. In these experiments pH decreased to 7.0-7.1 and standard [HO301] to 8-11 mmol per 1. During the first 3-4 min after the onset of exercise LA concentration of muscle tissue rose to 18-19 mumol per g wet weight in both series of experiments. During acidosis the highest average values for LA release from the muscle were about 1.1 mumoles per g per minute. During alkalosis LA permeation rate was nearly three times as high. As a consequence of increased rate of permeation, LA concentration of muscle tissue decreased more rapidly in alkalosis than in acidosis. In both series of experiments work per time and VO2 were practically equal during the first 5-6 min of exercise. Thereafter work per time and VO2 decreased more rapidly in acidosis than in alkalosis, a result which probably is due to higher LA concentration in muscle at this time in acidosis. It is concluded that LA permeation rate across muscle cell membrane is increased by high extracellular HCO3- concentration in combination with low H+ activity and vice versa."}
{"id": "PMID:239386", "title": "Renin measurement in blood collected from the efferent arteriole of the kidney of the rat.", "content": "Plasma renin could be detected in 16 nl of rat plasma by incubating at 50 degrees C, pH 6.2 with 20 mul of a rat renin substrate. In 60 nl samples it could be estimated and differences in concentration of 20% could be detected. Plasma renin concentration was measured in blood from the superficial efferent arterioles of a rat's kidney. The concentration of renin in different efferent arterioles of the same rat were similar. The renin concentration of efferent arteriolar blood was 361 plus or (-1)89 (S.D.) ng Al ml minus 1 (blood) hour (-1) which was not different from the renin concentration of simultaneously taken femoral artery blood (340 +/- 217). Plasma concentration can be measured in efferent arteriolar blood and will allow the control of renin secretion to be studied.", "contents": "Renin measurement in blood collected from the efferent arteriole of the kidney of the rat. Plasma renin could be detected in 16 nl of rat plasma by incubating at 50 degrees C, pH 6.2 with 20 mul of a rat renin substrate. In 60 nl samples it could be estimated and differences in concentration of 20% could be detected. Plasma renin concentration was measured in blood from the superficial efferent arterioles of a rat's kidney. The concentration of renin in different efferent arterioles of the same rat were similar. The renin concentration of efferent arteriolar blood was 361 plus or (-1)89 (S.D.) ng Al ml minus 1 (blood) hour (-1) which was not different from the renin concentration of simultaneously taken femoral artery blood (340 +/- 217). Plasma concentration can be measured in efferent arteriolar blood and will allow the control of renin secretion to be studied."}
{"id": "PMID:239387", "title": "Remote-controlled device for sampling arterial blood in unrestrained animals.", "content": "A device is described that allows remote-controlled sampling of arterial blood in unrestrained animals. An artery and a vein are dissected in local anesthesia and connected by a plastic catheter, the sampling catheter. The flow of arterial blood in this artificial shunt can be blocked by kinking the sampling catheter by a remote-controlled device. The blood thus trapped in the sampling catheter, of 0.45 ml volume is analyzed for PO2, PCO2, and pH using electrodes. The technique has been used in ducks and hens but can be applied to other vertebrate classes and to species of smaller body size.", "contents": "Remote-controlled device for sampling arterial blood in unrestrained animals. A device is described that allows remote-controlled sampling of arterial blood in unrestrained animals. An artery and a vein are dissected in local anesthesia and connected by a plastic catheter, the sampling catheter. The flow of arterial blood in this artificial shunt can be blocked by kinking the sampling catheter by a remote-controlled device. The blood thus trapped in the sampling catheter, of 0.45 ml volume is analyzed for PO2, PCO2, and pH using electrodes. The technique has been used in ducks and hens but can be applied to other vertebrate classes and to species of smaller body size."}
{"id": "PMID:239388", "title": "Microperfusion study of the kinetics of reabsorption of cycloleucine in early and late segments of the proximal convolution of the rat nephron.", "content": "The proximal tubular reabsorptive capacity for the non-metabolizable amino acid, cycloleucine, was studied in the rat nephron by stationary microperfusion. Tubular reabsorptive rates were greatest near the glomerulus and declined progressively along the convolution. A kinetic analysis of cycloleucine reabsorption in terms of luminal concentration revealed that this reduced transport rate was associated with an increase in the half-saturation constant of the kinetic curve, rather than a decrease in the maximum transport capacity. Since our previous findings with the metabolizable amino acid, -L-histidine, were identical we can conclude that this decline in reabsorption of neutral amino acids as a function of distance along the convolution is an intrinsic property of the transport system and is not related to tubule cell amino acid metabolism. The transport curves for cycloleucine absorption did not give a simple Michaelis-Menten relation but rather followed a course suggesting that more than one transport system might be involved.", "contents": "Microperfusion study of the kinetics of reabsorption of cycloleucine in early and late segments of the proximal convolution of the rat nephron. The proximal tubular reabsorptive capacity for the non-metabolizable amino acid, cycloleucine, was studied in the rat nephron by stationary microperfusion. Tubular reabsorptive rates were greatest near the glomerulus and declined progressively along the convolution. A kinetic analysis of cycloleucine reabsorption in terms of luminal concentration revealed that this reduced transport rate was associated with an increase in the half-saturation constant of the kinetic curve, rather than a decrease in the maximum transport capacity. Since our previous findings with the metabolizable amino acid, -L-histidine, were identical we can conclude that this decline in reabsorption of neutral amino acids as a function of distance along the convolution is an intrinsic property of the transport system and is not related to tubule cell amino acid metabolism. The transport curves for cycloleucine absorption did not give a simple Michaelis-Menten relation but rather followed a course suggesting that more than one transport system might be involved."}
{"id": "PMID:239390", "title": "Studies on deoxyribonucleases from Saccharomyces cerevisiae. Characterization of two endonuclease activities with a preference for double-stranded DNA.", "content": "Two new endonuclease activities, endonuclease B and endonuclease C, obtained from yeast nuclear preparations have been separated and partially characterized. Endonuclease B has a primary requirement for Mn2+ which cannot be replaced by Mg2+ or Ca2+, and makes single-strand scissions in double-stranded DNA. Endonculease C is activated by either Mn2+ or Mg2+, and makes single-strand scissions with Mg2+, while with Mn2+, scissions are made which result in double-strand breaks. Neither enzyme is active on denatured DNA, and both are inhibited by yeast RNA. Both enzymes exhibit pH optima at pH 5.0 and PH 7.2, and leave 5'-phosphoryl termini.", "contents": "Studies on deoxyribonucleases from Saccharomyces cerevisiae. Characterization of two endonuclease activities with a preference for double-stranded DNA. Two new endonuclease activities, endonuclease B and endonuclease C, obtained from yeast nuclear preparations have been separated and partially characterized. Endonuclease B has a primary requirement for Mn2+ which cannot be replaced by Mg2+ or Ca2+, and makes single-strand scissions in double-stranded DNA. Endonculease C is activated by either Mn2+ or Mg2+, and makes single-strand scissions with Mg2+, while with Mn2+, scissions are made which result in double-strand breaks. Neither enzyme is active on denatured DNA, and both are inhibited by yeast RNA. Both enzymes exhibit pH optima at pH 5.0 and PH 7.2, and leave 5'-phosphoryl termini."}
{"id": "PMID:239391", "title": "Interaction of Mg2+ ions with nucleoside triphosphates by phosphorus magnetic resonance spectroscopy.", "content": "The interaction of Mg2+ with nucleoside triphosphates: ATP, GTP, CTP and UTP has been studied by phosphorus magnetic resonance spectroscopy in aqueous solution. The results show that these four nucleotides behave similarly. Purine and Purimidine bases have almost no effect on the phosphate groups even in the N7 pK region of ATP and GTP. The Mg2+ ion binds not to the alpha and alpha but only to the beta phosphate group. The fixation is stronger at neutral pH than at acid pH.", "contents": "Interaction of Mg2+ ions with nucleoside triphosphates by phosphorus magnetic resonance spectroscopy. The interaction of Mg2+ with nucleoside triphosphates: ATP, GTP, CTP and UTP has been studied by phosphorus magnetic resonance spectroscopy in aqueous solution. The results show that these four nucleotides behave similarly. Purine and Purimidine bases have almost no effect on the phosphate groups even in the N7 pK region of ATP and GTP. The Mg2+ ion binds not to the alpha and alpha but only to the beta phosphate group. The fixation is stronger at neutral pH than at acid pH."}
{"id": "PMID:239392", "title": "Nucleoside 5'-phosphordiamidates, synthesis and some properties.", "content": "A simple way of preparing nucleoside 5'-phosphordiamidate is described. The procedure is based on the ammonolysis of nucleoside 5'-phosphordichloridates by dilute aqueous ammonium hydroxide. The behaviour of nucleoside phosphordiamidates under acidic and alkaline conditions is also reported. Alkaline hydrolysis results in the formation of the parent nucleoside, whereas one amide group can be removed selectively by mild acid hydrolysis. This property of nucleoside phosphordiamidates served as a basis for the elaboration of a simple synthesis of nucleoside phosphoramidates starting from nucleosides.", "contents": "Nucleoside 5'-phosphordiamidates, synthesis and some properties. A simple way of preparing nucleoside 5'-phosphordiamidate is described. The procedure is based on the ammonolysis of nucleoside 5'-phosphordichloridates by dilute aqueous ammonium hydroxide. The behaviour of nucleoside phosphordiamidates under acidic and alkaline conditions is also reported. Alkaline hydrolysis results in the formation of the parent nucleoside, whereas one amide group can be removed selectively by mild acid hydrolysis. This property of nucleoside phosphordiamidates served as a basis for the elaboration of a simple synthesis of nucleoside phosphoramidates starting from nucleosides."}
{"id": "PMID:239395", "title": "Effect of disulfiram and sodium diethyldithiocarbamate on tyrosine and dopamine-beta-hydroxylases activities in rat brain and heart.", "content": "Tyrosine hydroxylase and dopamine (DA)-beta-hydroxylase activities in rat brain and heart after disulfiram (DS) or diethyldithiocarbamate (DDC) administration have been determined in vitro and in vivo. DS and DDC in vitro stronger inhibit DA-beta-hydroxylase than tyrosine hydroxylase activity. 50% inhibition of tyrosine hydroxylase activity needed about twice higher concentrations of DS and DDC than the same inhibition of DA-beta-hydroxylase. Inhibition of the above enzymes in the in vivo experiments was DS or DDC dose dependent.", "contents": "Effect of disulfiram and sodium diethyldithiocarbamate on tyrosine and dopamine-beta-hydroxylases activities in rat brain and heart. Tyrosine hydroxylase and dopamine (DA)-beta-hydroxylase activities in rat brain and heart after disulfiram (DS) or diethyldithiocarbamate (DDC) administration have been determined in vitro and in vivo. DS and DDC in vitro stronger inhibit DA-beta-hydroxylase than tyrosine hydroxylase activity. 50% inhibition of tyrosine hydroxylase activity needed about twice higher concentrations of DS and DDC than the same inhibition of DA-beta-hydroxylase. Inhibition of the above enzymes in the in vivo experiments was DS or DDC dose dependent."}
{"id": "PMID:239396", "title": "Dependence of tyrosine and dopamine-beta-hydroxylases activities on disulfiram and diethyldithiocarbamate level in guinea pig brain and heart.", "content": "Tyrosine hydroxylase and dopamine-(DA)-beta-hydroxylase acitvities in guinea pig brain and heart were determined at various time after disulfiram (DS) and sodium diethyldithiocarbamate (DDC) injections. In the same tissues DS and DDC levels were measured. The linear relationship between the above enzymes activities and the levels of DDC in brain and heart has been found. The inactivation of the both enzymes is dependent on DDC content in tissues.", "contents": "Dependence of tyrosine and dopamine-beta-hydroxylases activities on disulfiram and diethyldithiocarbamate level in guinea pig brain and heart. Tyrosine hydroxylase and dopamine-(DA)-beta-hydroxylase acitvities in guinea pig brain and heart were determined at various time after disulfiram (DS) and sodium diethyldithiocarbamate (DDC) injections. In the same tissues DS and DDC levels were measured. The linear relationship between the above enzymes activities and the levels of DDC in brain and heart has been found. The inactivation of the both enzymes is dependent on DDC content in tissues."}
{"id": "PMID:239397", "title": "The central action of drugs affecting beta-adrenergic receptor. IV. The influence of intraventricularly administered drugs affecting beta-adrenergic receptor on blood pressure in rats.", "content": "Isoprenaline, propranolol, alprenol and sotalol administered intraventricularly (ivc) to anaesthetized rats induce hypotension. Propanolol and alprenolol given ivc to rats pretreated with isoprenaline increase blood pressure up to the values equal to those, previous to isoprenaline administration; another isoprenaline dose acts slightly hypotensively.", "contents": "The central action of drugs affecting beta-adrenergic receptor. IV. The influence of intraventricularly administered drugs affecting beta-adrenergic receptor on blood pressure in rats. Isoprenaline, propranolol, alprenol and sotalol administered intraventricularly (ivc) to anaesthetized rats induce hypotension. Propanolol and alprenolol given ivc to rats pretreated with isoprenaline increase blood pressure up to the values equal to those, previous to isoprenaline administration; another isoprenaline dose acts slightly hypotensively."}
{"id": "PMID:239400", "title": "Purification of rabbit liver guanine aminohydrolase.", "content": "Rabbit liver guanine aminohydrolase has been purified 1250-fold by utilization of an affinity chromatographic separation on 9-(p-aminoethoxyphenyl) guanine-Sepharose with 50% recovery of activity. Polyacrylamide gel electrophoresis of the purified preparations revealed several protein bans which corresponded to regions of enzyme activity measured on gels which had been run under the same conditons. Gel concentration studies of the protein migration rate showed that the protein bans differed in molecular size. The minimum molecular weight was 100,000 from gel permeation chromatography studies. The pH optimum was near pH 8 and the Km, with guanine as substrate was 5.6 x 10-6 M. The latter values are in close agreement with partially purified preparations described in the literature.", "contents": "Purification of rabbit liver guanine aminohydrolase. Rabbit liver guanine aminohydrolase has been purified 1250-fold by utilization of an affinity chromatographic separation on 9-(p-aminoethoxyphenyl) guanine-Sepharose with 50% recovery of activity. Polyacrylamide gel electrophoresis of the purified preparations revealed several protein bans which corresponded to regions of enzyme activity measured on gels which had been run under the same conditons. Gel concentration studies of the protein migration rate showed that the protein bans differed in molecular size. The minimum molecular weight was 100,000 from gel permeation chromatography studies. The pH optimum was near pH 8 and the Km, with guanine as substrate was 5.6 x 10-6 M. The latter values are in close agreement with partially purified preparations described in the literature."}
{"id": "PMID:239398", "title": "1-Haloacylpiperazines.", "content": "By direct acylation of piperazine with halogenocarboxylic acid chlorides in acid medium, the hydrochlorides of 1-haloacylpiperazines were obtained.", "contents": "1-Haloacylpiperazines. By direct acylation of piperazine with halogenocarboxylic acid chlorides in acid medium, the hydrochlorides of 1-haloacylpiperazines were obtained."}
{"id": "PMID:239401", "title": "Lipoteichoic acid: a specific inhibitor of autolysin activity in Pneumococcus.", "content": "The choline-containing pneumococcal lipoteichoic acid (Forssman antigen) is a powerful inhibitor of the homologous autolytic enzyme, an N-acetylmuramyl-L-alanine amidase (EC 3.5.1.28, MUCOPEPTIDE AMIDOHYDROLASE). Low concentrations of deoxycholate can reverse the inhibition. Wall teichoic acid preparations are inactive at several hundred-fold higher concentrations. Activation of an inactive form of autolysin by in vitro incubation with choline-containing cell walls is also inhibited by lipoteichoic acid. Addition of lipoteichoic acid to the growth medium of pneumococcal cultures causes chain formation, resistance to stationary phase lysis, and penicillin tolerance. It is suggested that a physiological role of lipoteichoic acids may be in the in vivo control of autolysin activity.", "contents": "Lipoteichoic acid: a specific inhibitor of autolysin activity in Pneumococcus. The choline-containing pneumococcal lipoteichoic acid (Forssman antigen) is a powerful inhibitor of the homologous autolytic enzyme, an N-acetylmuramyl-L-alanine amidase (EC 3.5.1.28, MUCOPEPTIDE AMIDOHYDROLASE). Low concentrations of deoxycholate can reverse the inhibition. Wall teichoic acid preparations are inactive at several hundred-fold higher concentrations. Activation of an inactive form of autolysin by in vitro incubation with choline-containing cell walls is also inhibited by lipoteichoic acid. Addition of lipoteichoic acid to the growth medium of pneumococcal cultures causes chain formation, resistance to stationary phase lysis, and penicillin tolerance. It is suggested that a physiological role of lipoteichoic acids may be in the in vivo control of autolysin activity."}
{"id": "PMID:239402", "title": "Separation of two responses to auxin by means of cytokinin inhibition.", "content": "A continuous growth apparatus was used to measure the effect of cytokinin on auxin-induced elongation. The soybean hypocotyl segments elicited a bi-phasic response to auxin that appeared to be two overlapping responses. The first response, which began 12 min after auxin addition, was not inhibited by cytokinin, even after long preincubation in cytokinin, but the second response to auxin, which began about 30 min after auxin addition, was completely inhibited by cytokinin. Such overlapping reactions are shown, depending on the amount of overlap, to yield a variety of summation reactions, many of which resemble rate-time curves that have been previously reported. We have shown that the transient first phase of auxin-induced elongation is very similar to acid-activated growth, while the second phase is long lasting and very likely identical to the long-term response to auxin, as extensively studied in Avena, soybean, and other elongating cells.", "contents": "Separation of two responses to auxin by means of cytokinin inhibition. A continuous growth apparatus was used to measure the effect of cytokinin on auxin-induced elongation. The soybean hypocotyl segments elicited a bi-phasic response to auxin that appeared to be two overlapping responses. The first response, which began 12 min after auxin addition, was not inhibited by cytokinin, even after long preincubation in cytokinin, but the second response to auxin, which began about 30 min after auxin addition, was completely inhibited by cytokinin. Such overlapping reactions are shown, depending on the amount of overlap, to yield a variety of summation reactions, many of which resemble rate-time curves that have been previously reported. We have shown that the transient first phase of auxin-induced elongation is very similar to acid-activated growth, while the second phase is long lasting and very likely identical to the long-term response to auxin, as extensively studied in Avena, soybean, and other elongating cells."}
{"id": "PMID:239403", "title": "Phenothiazine drugs: structure-activity relationships explained by a conformation that mimics dopamine.", "content": "The antischizophrenic activity of phenothiazine drugs and their tendency to elicit extrapyramidal symptoms are thought to involve blockade of synaptic dopamine receptors in the brain. Space filling molecular models show how favorable Van der Waal's interactions between the side chain amino of phenothiazines and the 2-substituent on ring A can promote a conformation mimicking dopamine. These Van der Waal's attractive forces can expain (i) the greater potency of drugs with trifluoromethyl rather than chlorine as a 2-substituent; (ii) the enhanced activity of phenothiazines with piperazine instead of alkylamino side chains; (iii) the increased potency associated with hydroxyethylpiperazines as contrasted to piperazine side chains; (iv) the greater potency of cis rather than trans thioxanthenes; and (v) the crucial location of the ring A substituent at carbon no. 2. Potential energy calculations support the observations with molecular models and suggest an active conformation for the phenothiazines.", "contents": "Phenothiazine drugs: structure-activity relationships explained by a conformation that mimics dopamine. The antischizophrenic activity of phenothiazine drugs and their tendency to elicit extrapyramidal symptoms are thought to involve blockade of synaptic dopamine receptors in the brain. Space filling molecular models show how favorable Van der Waal's interactions between the side chain amino of phenothiazines and the 2-substituent on ring A can promote a conformation mimicking dopamine. These Van der Waal's attractive forces can expain (i) the greater potency of drugs with trifluoromethyl rather than chlorine as a 2-substituent; (ii) the enhanced activity of phenothiazines with piperazine instead of alkylamino side chains; (iii) the increased potency associated with hydroxyethylpiperazines as contrasted to piperazine side chains; (iv) the greater potency of cis rather than trans thioxanthenes; and (v) the crucial location of the ring A substituent at carbon no. 2. Potential energy calculations support the observations with molecular models and suggest an active conformation for the phenothiazines."}
{"id": "PMID:239404", "title": "Increased particulate and decreased soluble guanylate cyclase activity in regenerating liver, fetal liver, and hepatoma.", "content": "We determined the activities of soluble and particulate guanylate cyclase [GTP pyrophosphatelyase (cyclizing); ?EC 4.6.1.2] IN REGENERATING RAT LIVER, FETAL AND NEONATAL RAT LIVER, AND HEPATOMA. TIn these tissues we found increased particulate and decreased soluble enzyme activities compared to normal adult rat liver. The particulate activity increased 12 hr after partial hepatectomy, reached maximal activity at 48 hr, and then declined. The soluble enzyme activity decreased within 8 hr and continued to decline. The activity of homogenates did not change. Guanylate cyclase activity was increased in plasma membrane and microsome fractions from regenerating liver. The increase in particulate activity was prevented with cycloheximide. Decreased soluble and increased particulate enzyme activities were found in fetal liver. After birth the soluble activity increased and the particulate activity decreased. Seven to 14 days after birth the activities of soluble and particulate fractions were similar to those of adult rat liver. In hepatoma 3924A, the activity of particulate guanylate cyclase was 9-fold greater and that of the soluble enzyme was 50% that of normal liver. These studies suggest that guanylate cyclase activity and its subcellular distribution may be related to liver growth through some unknown mechanism.", "contents": "Increased particulate and decreased soluble guanylate cyclase activity in regenerating liver, fetal liver, and hepatoma. We determined the activities of soluble and particulate guanylate cyclase [GTP pyrophosphatelyase (cyclizing); ?EC 4.6.1.2] IN REGENERATING RAT LIVER, FETAL AND NEONATAL RAT LIVER, AND HEPATOMA. TIn these tissues we found increased particulate and decreased soluble enzyme activities compared to normal adult rat liver. The particulate activity increased 12 hr after partial hepatectomy, reached maximal activity at 48 hr, and then declined. The soluble enzyme activity decreased within 8 hr and continued to decline. The activity of homogenates did not change. Guanylate cyclase activity was increased in plasma membrane and microsome fractions from regenerating liver. The increase in particulate activity was prevented with cycloheximide. Decreased soluble and increased particulate enzyme activities were found in fetal liver. After birth the soluble activity increased and the particulate activity decreased. Seven to 14 days after birth the activities of soluble and particulate fractions were similar to those of adult rat liver. In hepatoma 3924A, the activity of particulate guanylate cyclase was 9-fold greater and that of the soluble enzyme was 50% that of normal liver. These studies suggest that guanylate cyclase activity and its subcellular distribution may be related to liver growth through some unknown mechanism."}
{"id": "PMID:239405", "title": "Cell surface changes accompanying viral transformation: N-acetylneuraminic acid ectotransferase system activity.", "content": "The activity of the sialyl ectotransferase system of normal chick embryo fibroblasts (CEF) and chick embryo fibroblasts transformed with the Schmidt-Ruppin strain of Rous sarcoma virus (SR-RSV) have been compared. Neuraminidase treatment of the intact cells increased the sialyl ectotransferase system activity of control and transformed cells two to three times. The ectotransferase system activity increased as the pH was decreased from 7.8 to 6.0. The temperature optimum for both systems was 40 degrees C. Approximately 60% of the 14C-sialic acid incorporated at pH 6.5 or above could be removed with neuraminidase. The activity of the transformed cell system with or without neuraminidase treatment was more stimulated by addition of Mn2+ ions, particularly above pH 7.0. This difference in ion sensitivity indicates that a different cell surface phenomenon is being studied after transformation.", "contents": "Cell surface changes accompanying viral transformation: N-acetylneuraminic acid ectotransferase system activity. The activity of the sialyl ectotransferase system of normal chick embryo fibroblasts (CEF) and chick embryo fibroblasts transformed with the Schmidt-Ruppin strain of Rous sarcoma virus (SR-RSV) have been compared. Neuraminidase treatment of the intact cells increased the sialyl ectotransferase system activity of control and transformed cells two to three times. The ectotransferase system activity increased as the pH was decreased from 7.8 to 6.0. The temperature optimum for both systems was 40 degrees C. Approximately 60% of the 14C-sialic acid incorporated at pH 6.5 or above could be removed with neuraminidase. The activity of the transformed cell system with or without neuraminidase treatment was more stimulated by addition of Mn2+ ions, particularly above pH 7.0. This difference in ion sensitivity indicates that a different cell surface phenomenon is being studied after transformation."}
{"id": "PMID:239409", "title": "Studies of properties and potential applications of some soluble salts of cellulose acetate phthalate. Part 1: rheological behavior and aging effect.", "content": "Rheological behaviour for solutions of the sodium, ammonium, and triethanolamie salts of cellulose acetate phthalate was studied. The comparative resistance to microbial growth and to changes in pH values exhibited by these solutions on storage was also investigated. The results indicated that the viscosities of these solutions were temperature and concentration dependent and that increasing the rate of shear produced only a slight increase of viscosity. Solutions of ammonium and the triethanolamine salts did not support any apparent microbial growth during storage at room temperature of three weeks, but the sodium salt appeared to suffer from microbial contamination. However, the use of a mixture of 0.15% methylparaben and 0.05% propylparaben prevented such contamination. The pH values of all the slat solutions studied appeared to decrease on storage.", "contents": "Studies of properties and potential applications of some soluble salts of cellulose acetate phthalate. Part 1: rheological behavior and aging effect. Rheological behaviour for solutions of the sodium, ammonium, and triethanolamie salts of cellulose acetate phthalate was studied. The comparative resistance to microbial growth and to changes in pH values exhibited by these solutions on storage was also investigated. The results indicated that the viscosities of these solutions were temperature and concentration dependent and that increasing the rate of shear produced only a slight increase of viscosity. Solutions of ammonium and the triethanolamine salts did not support any apparent microbial growth during storage at room temperature of three weeks, but the sodium salt appeared to suffer from microbial contamination. However, the use of a mixture of 0.15% methylparaben and 0.05% propylparaben prevented such contamination. The pH values of all the slat solutions studied appeared to decrease on storage."}
{"id": "PMID:239411", "title": "Factors effecting drug release from inert matrices. Part 1: effects of surfactants on the release of quinine sulfate.", "content": "Dissolution rate studies of quinine sulfate from polyamide matrices, in simulated gastric and intestinal fluids, are carried out in the presence of hexadecyltrimethylammonium bromide, sodium lauryl sulfate and polyoxyethylene (50) stearate surfactants. The results obtained show that dissolution rate is dependent upon the pH of the disolution media and the type and concentration of surfactant. The solubilization effect of surfactants is also examined and the findings are discussed.", "contents": "Factors effecting drug release from inert matrices. Part 1: effects of surfactants on the release of quinine sulfate. Dissolution rate studies of quinine sulfate from polyamide matrices, in simulated gastric and intestinal fluids, are carried out in the presence of hexadecyltrimethylammonium bromide, sodium lauryl sulfate and polyoxyethylene (50) stearate surfactants. The results obtained show that dissolution rate is dependent upon the pH of the disolution media and the type and concentration of surfactant. The solubilization effect of surfactants is also examined and the findings are discussed."}
{"id": "PMID:239412", "title": "Characterization of the rabbit detrusor response to histamine through pharmacologic antagonism.", "content": "The various effects of histamine on smooth muscles and other tissues are thought to be mediated by two pharmacologically distinct receptors, H1 and H2 types. These receptors are defined in terms of thier susceptibility to blockade by pyrilamine (type H1) or burimamide (type H2). In this study selective antagonism of the spasmodic effects of histamine on isolated strips of rabbit detrusor has shown that the response is mediated by H1 receptors, with no evidence of H2 activity. The p-A2 of the pyrilaminehistamine antagonism is 9.3. The histamine response is susceptible to muscarinic blockade (atropine and propantheline) but not to nicotinic blockade (hexamethonium). Adrenergic blocking agents propranolol (10 minus 4 M) and phenoxybenzamine (10 minus 8 M) do antagonize the contractile response, but this does not appear to be indicative of adrenergic mediation.", "contents": "Characterization of the rabbit detrusor response to histamine through pharmacologic antagonism. The various effects of histamine on smooth muscles and other tissues are thought to be mediated by two pharmacologically distinct receptors, H1 and H2 types. These receptors are defined in terms of thier susceptibility to blockade by pyrilamine (type H1) or burimamide (type H2). In this study selective antagonism of the spasmodic effects of histamine on isolated strips of rabbit detrusor has shown that the response is mediated by H1 receptors, with no evidence of H2 activity. The p-A2 of the pyrilaminehistamine antagonism is 9.3. The histamine response is susceptible to muscarinic blockade (atropine and propantheline) but not to nicotinic blockade (hexamethonium). Adrenergic blocking agents propranolol (10 minus 4 M) and phenoxybenzamine (10 minus 8 M) do antagonize the contractile response, but this does not appear to be indicative of adrenergic mediation."}
{"id": "PMID:239413", "title": "Effect of release of endogenous gastrin on myoelectrical and mechanical activity of isolated canine stomach.", "content": "The myoelectrical and mechanical activities of the totally isolated, canine stomachs were recorded using five sets of bipolar silver-wire electrodes and one strain gauge. Stomachs were perfused extracorporeally with the blood of living supporting dogs which served as oxygenators and dialysers. Each supporting dog had a permanent antral pouch, accessible for the purpose of irrigation. To suppress the release of endogenous gastrin, this antral pouch and the antrum of the ex vivo stomach were irrigated with acid (pH 3). To induce the release of gastrin, one or both antra were irrigated with 0.2-percent acetylcholine or with 1 M glycine. To compare the action of endogenous gastrin with exogenous gastrin-like peptide, pentagastrin was infused into the gastric artery in doses of 4 mug/h and 8 mug/h. Control recordings were done during the acid irrigation. Endogenous gastrin released from antra by acetylcholine or glycine caused identical changes in the recordings as exogenous pentagastrin. There was a marked increase in the frequency of electrical control activity and of gastric contractions recorded as increased mechanical response. The results indicate that the ex vivo stomach can be used for study of the effect of endogenous gastrin musculature activity under the experimental conditions described.", "contents": "Effect of release of endogenous gastrin on myoelectrical and mechanical activity of isolated canine stomach. The myoelectrical and mechanical activities of the totally isolated, canine stomachs were recorded using five sets of bipolar silver-wire electrodes and one strain gauge. Stomachs were perfused extracorporeally with the blood of living supporting dogs which served as oxygenators and dialysers. Each supporting dog had a permanent antral pouch, accessible for the purpose of irrigation. To suppress the release of endogenous gastrin, this antral pouch and the antrum of the ex vivo stomach were irrigated with acid (pH 3). To induce the release of gastrin, one or both antra were irrigated with 0.2-percent acetylcholine or with 1 M glycine. To compare the action of endogenous gastrin with exogenous gastrin-like peptide, pentagastrin was infused into the gastric artery in doses of 4 mug/h and 8 mug/h. Control recordings were done during the acid irrigation. Endogenous gastrin released from antra by acetylcholine or glycine caused identical changes in the recordings as exogenous pentagastrin. There was a marked increase in the frequency of electrical control activity and of gastric contractions recorded as increased mechanical response. The results indicate that the ex vivo stomach can be used for study of the effect of endogenous gastrin musculature activity under the experimental conditions described."}
{"id": "PMID:239414", "title": "Evaluation of a new oral beta2-adrenoceptor stimulant bronchodilator, terbutaline.", "content": "A double-blind crossover comparison was made of the effect of orally administered terbutaline (a new adrenergic drug with major action on beta2-receptors), ephedrine, and placebo in 15 patients with obstructive airways disease. Serial determination of ventilatory tests, arterial gas tensions, arterial blood pressure, ECG, blood chemistries, and urinalysis were made before and after administration of the tested drug. Terbutaline (5 mg) was found to be an effective bronchodilator with minimal side effects and an earlier onset and longer duration of action than ephedrine (25 mg).", "contents": "Evaluation of a new oral beta2-adrenoceptor stimulant bronchodilator, terbutaline. A double-blind crossover comparison was made of the effect of orally administered terbutaline (a new adrenergic drug with major action on beta2-receptors), ephedrine, and placebo in 15 patients with obstructive airways disease. Serial determination of ventilatory tests, arterial gas tensions, arterial blood pressure, ECG, blood chemistries, and urinalysis were made before and after administration of the tested drug. Terbutaline (5 mg) was found to be an effective bronchodilator with minimal side effects and an earlier onset and longer duration of action than ephedrine (25 mg)."}
{"id": "PMID:239415", "title": "Network analysis of dendritic fields of pyramidal cells in neocortex and Purkinje cells in the cerebellum of the rat.", "content": "The connectivity within the dendritic array of Purkinje cells in the cerebellum and pyramidal cells of the neocortex of the rat, stained by the Golgi-Cox method, has been quantified by the method of network analysis. Connectivity was characterized either by applying the system of Strahler ordering, which assigns a relative order of magnitude to each branch of the arborescence or by the identification of unique topological branching patterns within the tree. The former method has been used to define the entire dendritic array of the Purkinje cell and the apical system of neocortical pyramids. It has been shown that the relation between the numbers of branches of successive Strahler order in Purkinje cells form an inverse geometric series in which the highest order is unity and the ratio between successive orders approximates to 3. On the other hand, the apical dendrites of neocortical pyramids exhibit two bifurcation ratios, i.e. a ratio of 3 between low orders and a ratio of 4 between higher orders. A computer simulation technique was used to generate networks of a size comparable with the Purkinje cell networks and grown according to two hypotheses namely, a 'terminal growth model' in which additional segments were added randomly to the terminal branches only and a 'segmental growth model' in which additional segments were added randomly to any branch within the array including terminal branches. Subsequent ordering of the simulated trees revealed that the relation between the numbers of successive orders for networks generated according to the 'segmental model' tended towards an inverse geometric series with a ratio of 4 and that generated according to the 'terminal model' tended towards a ratio of 3. This result showed that the dendritic tree of Purkinje cells grow in a manner indistinguishable from a system adding branches to random terminal segments and that neocortical apical dendrites add their collateral branches to random segments of the apical shaft but that the collateral branches themselves grow by random terminal branching. The possibility that such conclusions may be influenced by loss of branches incurred by either a failure of impregnation, by sectioning, or by environmental influences was investigated by means of a computer technique...", "contents": "Network analysis of dendritic fields of pyramidal cells in neocortex and Purkinje cells in the cerebellum of the rat. The connectivity within the dendritic array of Purkinje cells in the cerebellum and pyramidal cells of the neocortex of the rat, stained by the Golgi-Cox method, has been quantified by the method of network analysis. Connectivity was characterized either by applying the system of Strahler ordering, which assigns a relative order of magnitude to each branch of the arborescence or by the identification of unique topological branching patterns within the tree. The former method has been used to define the entire dendritic array of the Purkinje cell and the apical system of neocortical pyramids. It has been shown that the relation between the numbers of branches of successive Strahler order in Purkinje cells form an inverse geometric series in which the highest order is unity and the ratio between successive orders approximates to 3. On the other hand, the apical dendrites of neocortical pyramids exhibit two bifurcation ratios, i.e. a ratio of 3 between low orders and a ratio of 4 between higher orders. A computer simulation technique was used to generate networks of a size comparable with the Purkinje cell networks and grown according to two hypotheses namely, a 'terminal growth model' in which additional segments were added randomly to the terminal branches only and a 'segmental growth model' in which additional segments were added randomly to any branch within the array including terminal branches. Subsequent ordering of the simulated trees revealed that the relation between the numbers of successive orders for networks generated according to the 'segmental model' tended towards an inverse geometric series with a ratio of 4 and that generated according to the 'terminal model' tended towards a ratio of 3. This result showed that the dendritic tree of Purkinje cells grow in a manner indistinguishable from a system adding branches to random terminal segments and that neocortical apical dendrites add their collateral branches to random segments of the apical shaft but that the collateral branches themselves grow by random terminal branching. The possibility that such conclusions may be influenced by loss of branches incurred by either a failure of impregnation, by sectioning, or by environmental influences was investigated by means of a computer technique..."}
{"id": "PMID:239416", "title": "The behavioural final common path.", "content": "In this paper it is argued that any model of the motivational (i.e. reversible) processes governing the behaviour of an animal can be represented by means of isoclines in a multidimensional 'causal-factor space'. The argument is axiomatic, based upon the two prime assumptions: that (1) it is always possible to classify the behavioural repertoire of a species in such a way that the classes are mutually exclusive in the sense that the members of different classes cannot occur simultaneously, and (2) these incompatible actions are uniquely determined by a particular set of causal factors. The isoclines join all points in the space which present a given 'degree of competitiveness' of a particular 'candidate' for overt behavioural expression. The competition between candidates is an inevitable consequence of the fact that animals cannot 'do more than one thing at a time', and is envisaged as taking place in the behavioural final common path. An empirical method of determining the motivational state (i.e. point in causal-factor space) is outlined. This is a 'relative' method, independent of the arbitrary calibration of the axes of the causal-factor space. It is shown that an arbitrary scale of measurement along any two axes of the causal-factor space is all that is necessary for empirical determination of the shape of a motivational isocline. Experiments in which this method has been applied to the measurement of hunger and thirst in doves are outlined, and the results are discussed in terms of their implications for motivation theory in general.", "contents": "The behavioural final common path. In this paper it is argued that any model of the motivational (i.e. reversible) processes governing the behaviour of an animal can be represented by means of isoclines in a multidimensional 'causal-factor space'. The argument is axiomatic, based upon the two prime assumptions: that (1) it is always possible to classify the behavioural repertoire of a species in such a way that the classes are mutually exclusive in the sense that the members of different classes cannot occur simultaneously, and (2) these incompatible actions are uniquely determined by a particular set of causal factors. The isoclines join all points in the space which present a given 'degree of competitiveness' of a particular 'candidate' for overt behavioural expression. The competition between candidates is an inevitable consequence of the fact that animals cannot 'do more than one thing at a time', and is envisaged as taking place in the behavioural final common path. An empirical method of determining the motivational state (i.e. point in causal-factor space) is outlined. This is a 'relative' method, independent of the arbitrary calibration of the axes of the causal-factor space. It is shown that an arbitrary scale of measurement along any two axes of the causal-factor space is all that is necessary for empirical determination of the shape of a motivational isocline. Experiments in which this method has been applied to the measurement of hunger and thirst in doves are outlined, and the results are discussed in terms of their implications for motivation theory in general."}
{"id": "PMID:239417", "title": "Composition and structure of the pericellular environment. Physiological function and chemical composition of pericellular proteoglycan (an evolutionary view).", "content": "Connective tissue cells exist in a meshwork of insoluble fibres, the interstices of which are filled with soluble, high molecular mass, anionic material of a predominantly carbohydrate nature. The interactions of fibres with the interfibrillar material are central to the discussion of connective tissue physiology. As with all soluble polymers, the interfibrillar polyanion tends to \"swell' and the tangled mass of chains offers considerable resistance to penetration by the large insoluble fibres. The consequent pressure to \"inflate' the fibrous network is important in giving elasticity to cartilage, transparency to cornea, etc. Branched structures (of proteoglycans) and straight-chain forms (of hyaluronate) are compared for their ability to fulfil these functions. Apart from their physical (\"non-specific') roles proteoglycans and glycosaminoglycans are able to interact physicochemically with, for example, collagen in ways which show considerable specificity, and which presumably are important in the laying down of the fibrous network as well as in maintaining its mechanical integrity. It is proposed that the role played by radiation, particularly as mediated via the hydrated electron (eaq) was dominant in the pre- and post-biotic evolution of pericellular environments.", "contents": "Composition and structure of the pericellular environment. Physiological function and chemical composition of pericellular proteoglycan (an evolutionary view). Connective tissue cells exist in a meshwork of insoluble fibres, the interstices of which are filled with soluble, high molecular mass, anionic material of a predominantly carbohydrate nature. The interactions of fibres with the interfibrillar material are central to the discussion of connective tissue physiology. As with all soluble polymers, the interfibrillar polyanion tends to \"swell' and the tangled mass of chains offers considerable resistance to penetration by the large insoluble fibres. The consequent pressure to \"inflate' the fibrous network is important in giving elasticity to cartilage, transparency to cornea, etc. Branched structures (of proteoglycans) and straight-chain forms (of hyaluronate) are compared for their ability to fulfil these functions. Apart from their physical (\"non-specific') roles proteoglycans and glycosaminoglycans are able to interact physicochemically with, for example, collagen in ways which show considerable specificity, and which presumably are important in the laying down of the fibrous network as well as in maintaining its mechanical integrity. It is proposed that the role played by radiation, particularly as mediated via the hydrated electron (eaq) was dominant in the pre- and post-biotic evolution of pericellular environments."}
{"id": "PMID:239418", "title": "Structural and histochemical aspects of the pericellular environment in cartilage.", "content": "Mature cartilage contains pericellular regions of matrix of fine texture, consisting of filamentous material and granules containing proteoglycan. Intercellular matrix contains collagen fibres with structural elements resembling those of the pericellular regions in the spaces between the fibres. Membrane bound bodies may be present at the margin of the pericellular region. Histochemically, chondroitin sulphate is found in the pericellular region in all zones but keratan sulphate is similarly stainable only in the deep zones of ageing cartilage.", "contents": "Structural and histochemical aspects of the pericellular environment in cartilage. Mature cartilage contains pericellular regions of matrix of fine texture, consisting of filamentous material and granules containing proteoglycan. Intercellular matrix contains collagen fibres with structural elements resembling those of the pericellular regions in the spaces between the fibres. Membrane bound bodies may be present at the margin of the pericellular region. Histochemically, chondroitin sulphate is found in the pericellular region in all zones but keratan sulphate is similarly stainable only in the deep zones of ageing cartilage."}
{"id": "PMID:239419", "title": "Connective tissue cells, cell proliferation and synthesis of extracellular matrix-a review.", "content": "The ubiquitous connective tissues contain a wide range of cells including fibroblasts, osteoblasts and chondroblasts. Recently it has been demonstrated that another principal cell of the connective tissue is the smooth muscle cell in several organ systems. These have been shown to be responsible for the synthesis of the connective tissue matrix components of the uterine myometrium and of the arterial system, including collagen, both elastic fibre proteins and glycosaminoglycan. Microtubule inhibitors such as colchicine and vinblastine, and iron chelators such as alpha,alpha -dipyridyl have been used to study their morphologic and chemical effects on collagen synthesis and secretion. Colchicine produces an increase in large Golgi-associated vacuoles, which sometimes contain material reminiscent of aggregates of collagen macromolecules. Vinblastine produces alterations in the endoplasmic reticulum cisternae similar to alterations seen in ascorbic acid deficiency, and alpha,alpha-dipyridyl increases the frequency of regions in cells, interpretable as potential sites of communication of rough endoplasmic reticulum cisternae with the cell surface. Ferritin conjugated anti-procallagen sera were used to localize procollagen in cells and demonstrated procollagen not only in the cisternae of rough endoplasmic reticulum but in all of the elements of the Golgi complex as well. The studies reported in this review have shown that in cell culture arterial smooth muscle will produce not only the microfibrillar protein of the elastic fibre but soluble and/or insoluble elastin as well. Recent studies on serum factors responsible for the proliferation of connective tissue cells have demonstrated that at least one of the principal factors responsible for fibroblast and/or smooth muscle cell proliferation in culture is derived from thrombocytes. Medium containing serum derived from cell-free plasma lacks most of this proliferative effect which can be reinstated when platelets are present during recalcification to form serum. This effect is due to the platelet release reaction as shown by combining supernatant factors derived from platelets exposed to purified thrombin to cell-free, plasma derived serum. Studies with macrophages have also suggested that phagocytic macrophages release factor(s) into a cell culture medium that may also participate in stimulating fibroblasts to proliferate in vitro. The means by which these factors stimulate fibroblast proliferation and connective tissue synthesis remains to be elucidated.", "contents": "Connective tissue cells, cell proliferation and synthesis of extracellular matrix-a review. The ubiquitous connective tissues contain a wide range of cells including fibroblasts, osteoblasts and chondroblasts. Recently it has been demonstrated that another principal cell of the connective tissue is the smooth muscle cell in several organ systems. These have been shown to be responsible for the synthesis of the connective tissue matrix components of the uterine myometrium and of the arterial system, including collagen, both elastic fibre proteins and glycosaminoglycan. Microtubule inhibitors such as colchicine and vinblastine, and iron chelators such as alpha,alpha -dipyridyl have been used to study their morphologic and chemical effects on collagen synthesis and secretion. Colchicine produces an increase in large Golgi-associated vacuoles, which sometimes contain material reminiscent of aggregates of collagen macromolecules. Vinblastine produces alterations in the endoplasmic reticulum cisternae similar to alterations seen in ascorbic acid deficiency, and alpha,alpha-dipyridyl increases the frequency of regions in cells, interpretable as potential sites of communication of rough endoplasmic reticulum cisternae with the cell surface. Ferritin conjugated anti-procallagen sera were used to localize procollagen in cells and demonstrated procollagen not only in the cisternae of rough endoplasmic reticulum but in all of the elements of the Golgi complex as well. The studies reported in this review have shown that in cell culture arterial smooth muscle will produce not only the microfibrillar protein of the elastic fibre but soluble and/or insoluble elastin as well. Recent studies on serum factors responsible for the proliferation of connective tissue cells have demonstrated that at least one of the principal factors responsible for fibroblast and/or smooth muscle cell proliferation in culture is derived from thrombocytes. Medium containing serum derived from cell-free plasma lacks most of this proliferative effect which can be reinstated when platelets are present during recalcification to form serum. This effect is due to the platelet release reaction as shown by combining supernatant factors derived from platelets exposed to purified thrombin to cell-free, plasma derived serum. Studies with macrophages have also suggested that phagocytic macrophages release factor(s) into a cell culture medium that may also participate in stimulating fibroblasts to proliferate in vitro. The means by which these factors stimulate fibroblast proliferation and connective tissue synthesis remains to be elucidated."}
{"id": "PMID:239420", "title": "Measurement of pH and ionic composition of pericellular sites.", "content": "The development of ion selective microelectrodes has made it possible to measure the normal steady state in the pericellular environment together with ion fluxes in response to physiological or pathological disturbances. Combined intracellular and extracellular measurements indicate that there is a considerable range of ability between various types of cells in the efficiency with which they can tolerate changes in pericellular conditions. Macrophages are extremely tolerant while cells of the cerebral cortex require a very finely controlled local environment. Combination of ion selective probes with microelectrodes which measure substrate and oxygen availability extend the information which can be obtained about ionic composition of cellular environment and the factors which are important in its homostasis.", "contents": "Measurement of pH and ionic composition of pericellular sites. The development of ion selective microelectrodes has made it possible to measure the normal steady state in the pericellular environment together with ion fluxes in response to physiological or pathological disturbances. Combined intracellular and extracellular measurements indicate that there is a considerable range of ability between various types of cells in the efficiency with which they can tolerate changes in pericellular conditions. Macrophages are extremely tolerant while cells of the cerebral cortex require a very finely controlled local environment. Combination of ion selective probes with microelectrodes which measure substrate and oxygen availability extend the information which can be obtained about ionic composition of cellular environment and the factors which are important in its homostasis."}
{"id": "PMID:239421", "title": "Electrostatic interactions at the plasma membrane.", "content": "Hydrogen-ion titration has been used to detect the presence of charged groups on the human red-cell plasma membrane. The findings are discussed in terms of the effect of the local environment on electrostatic interactions between the charged groups.", "contents": "Electrostatic interactions at the plasma membrane. Hydrogen-ion titration has been used to detect the presence of charged groups on the human red-cell plasma membrane. The findings are discussed in terms of the effect of the local environment on electrostatic interactions between the charged groups."}
{"id": "PMID:239423", "title": "Influence of the cells on the pericellular environment. The effect of hyaluronic acid on proteoglycan synthesis and secretion by chondrocytes of adult cartilage.", "content": "The chondrocyte is a specialized cell that synthesizes proteoglycans of a type found only in cartilage and nucleus pulposus. These proteoglycans are distinct in forming multiple aggregates of unique structure in which hyaluronic acid provides a central chain to which many proteoglycan molecules are bound at one end only. Chondrocytes were isolated from adult cartilage and used in suspension culture to test the effect of compounds in the medium on the synthesis of proteoglycans. Hyaluronic acid alone, among a number of compounds extracted from or analogous to those in cartilage, reduced the incorporation of [35S] sulphate into macromolecular material. Oligosaccharides of hyaluronic acid of the size of decasaccharides and above also had this effect but hyaluronic acid already bound to proteoglycan did not. The proportion of total labelled material associated with the cells increased at the expense of that in the medium. Treatment of the cells with trypsin abolished the effect of hyaluronic acid but treatment with chondroitinase did not. It is suggested that hyaluronic acid interacts with proteoglycans at the cell surface by a specific mechanism similar to that involved in proteoglycan aggregation, as a result of which the secretion and synthesis of proteoglycans is reduced.", "contents": "Influence of the cells on the pericellular environment. The effect of hyaluronic acid on proteoglycan synthesis and secretion by chondrocytes of adult cartilage. The chondrocyte is a specialized cell that synthesizes proteoglycans of a type found only in cartilage and nucleus pulposus. These proteoglycans are distinct in forming multiple aggregates of unique structure in which hyaluronic acid provides a central chain to which many proteoglycan molecules are bound at one end only. Chondrocytes were isolated from adult cartilage and used in suspension culture to test the effect of compounds in the medium on the synthesis of proteoglycans. Hyaluronic acid alone, among a number of compounds extracted from or analogous to those in cartilage, reduced the incorporation of [35S] sulphate into macromolecular material. Oligosaccharides of hyaluronic acid of the size of decasaccharides and above also had this effect but hyaluronic acid already bound to proteoglycan did not. The proportion of total labelled material associated with the cells increased at the expense of that in the medium. Treatment of the cells with trypsin abolished the effect of hyaluronic acid but treatment with chondroitinase did not. It is suggested that hyaluronic acid interacts with proteoglycans at the cell surface by a specific mechanism similar to that involved in proteoglycan aggregation, as a result of which the secretion and synthesis of proteoglycans is reduced."}
{"id": "PMID:239424", "title": "Glycosaminoglycan turn-over in articular cartilage.", "content": "Glycosaminoglycan turn-over has been studied both in vivo and in vitro, by using sodium [35S]sulphate as a precursor. The in vivo experiments were performed on rabbits and dogs, taking special care to monitor the 35S radioactivity in the serum throughout the experiment and to measure the radioactivity due to unincorporated inorganic [35S]sulphate in cartilage at the end of each experiment, in addition to that due to incorporated sulphate. The inorganic sulphate content of the serum was also determined as well as the distribution coefficient for the inorganic sulphate ion between cartilage and serum. From this information it was possible to calculate accurately the rate of sulphate uptake by cartilage in vivo and hence the turn-over rate. Experiments were then performed in vitro on cartilage from rabbits and dogs and the in vivo and in vitro results were compared. A very good agreement was obtained between the two sets of results. Studies were then carried out under exactly the same in vitro conditions on human articular cartilage and it was thus possible to obtain a turn-over rate for the latter which one could trust was close to the actual in vivo value. The mean half-lives thus obtained varied from 45 days for the young rabbit to 150 days for the adult dog and 800 days for the human femoral head. In human cartilage there were considerable variations in turn-over rate within a single joint as a function of depth below the surface, and between different joints. Thus, while the mean half-life for the human femoral head is 800 days, that for the femoral condyle is 300 days. Cartilage from osteoarthrosic femoral heads did not appear to differ much with respect to sulphate uptake from the normal specimens although the turn-over rates were somewhat higher.", "contents": "Glycosaminoglycan turn-over in articular cartilage. Glycosaminoglycan turn-over has been studied both in vivo and in vitro, by using sodium [35S]sulphate as a precursor. The in vivo experiments were performed on rabbits and dogs, taking special care to monitor the 35S radioactivity in the serum throughout the experiment and to measure the radioactivity due to unincorporated inorganic [35S]sulphate in cartilage at the end of each experiment, in addition to that due to incorporated sulphate. The inorganic sulphate content of the serum was also determined as well as the distribution coefficient for the inorganic sulphate ion between cartilage and serum. From this information it was possible to calculate accurately the rate of sulphate uptake by cartilage in vivo and hence the turn-over rate. Experiments were then performed in vitro on cartilage from rabbits and dogs and the in vivo and in vitro results were compared. A very good agreement was obtained between the two sets of results. Studies were then carried out under exactly the same in vitro conditions on human articular cartilage and it was thus possible to obtain a turn-over rate for the latter which one could trust was close to the actual in vivo value. The mean half-lives thus obtained varied from 45 days for the young rabbit to 150 days for the adult dog and 800 days for the human femoral head. In human cartilage there were considerable variations in turn-over rate within a single joint as a function of depth below the surface, and between different joints. Thus, while the mean half-life for the human femoral head is 800 days, that for the femoral condyle is 300 days. Cartilage from osteoarthrosic femoral heads did not appear to differ much with respect to sulphate uptake from the normal specimens although the turn-over rates were somewhat higher."}
{"id": "PMID:239425", "title": "The secretion of enzymes into the pericellular environment.", "content": "Connective tissue cells are capable of both synthesizing and degrading the macromolecular components of the extracellular matrix. The degradation of proteoglycan and collagen has been shown to be associated with the extracellular release of proteolytic enzymes, some of which are of lysosomal origin. The identity in carilage of two previously unrecognized proteases, capable of proteoglycan breakdown (CPGases), has recently been achieved by the use of a new assay for proteoglycan degradation. These enzymes have been shown to be synthesized and released in response to vitamin A. The third proteoglycan degrading enzyme of connective tissue cells, cathepsin D, has been located in the pericellular environment by trapping with specific antibody and the pattern of release studied in organ culture, experimental arthritis and in human rheumatoid tissues. The secretion of this enzyme and possibly also of the other CPGases is thought to be of importance in the local (pericellular) turnover of matrix macromolecules and, in association with collagenase, to be the cause of the excessive degradation in the pannus erosion of articular cartilage in rheumatoid arthritis.", "contents": "The secretion of enzymes into the pericellular environment. Connective tissue cells are capable of both synthesizing and degrading the macromolecular components of the extracellular matrix. The degradation of proteoglycan and collagen has been shown to be associated with the extracellular release of proteolytic enzymes, some of which are of lysosomal origin. The identity in carilage of two previously unrecognized proteases, capable of proteoglycan breakdown (CPGases), has recently been achieved by the use of a new assay for proteoglycan degradation. These enzymes have been shown to be synthesized and released in response to vitamin A. The third proteoglycan degrading enzyme of connective tissue cells, cathepsin D, has been located in the pericellular environment by trapping with specific antibody and the pattern of release studied in organ culture, experimental arthritis and in human rheumatoid tissues. The secretion of this enzyme and possibly also of the other CPGases is thought to be of importance in the local (pericellular) turnover of matrix macromolecules and, in association with collagenase, to be the cause of the excessive degradation in the pannus erosion of articular cartilage in rheumatoid arthritis."}
{"id": "PMID:239426", "title": "Influence of the pericellular environment on the cells. The role of mucopolysaccharides in the protection of cartilage cells against immune reactions.", "content": "Problems related to rheumatoid arthritis have been investigated by a group at Cambridge using the organ culture technique. Since auto-allergic reactions may be concerned in the chronicity of the disease, the effects of reactive complement-sufficient antisera (AS+C') on embryonic and post-foetal cartilage were examined. The cartilaginous limb bone rudiments enlarged to several times their original volume in control medium, but in the presence of AS+C' they gradually disintegrated, owing to the breakdown of the cartilage matrix; only the superficial cells of the enveloping soft connective tissue were killed, however. Provided breakdown had not advanced too far, the effects of AS+C' were reversible. It was not clear how AS+C' produced these changes, since cartilage matrix is impermeable to molecules as large as the immunoglobulins. To find whether there was a difference in permeability between embryonic and post-foetal cartilage, similar experiments were made on the articular cartilage of young pigs. AS+C' had no effect on pure articular cartilage, and it was shown immunohistochemically that IgG did not penetrate beyond the most superficial layer of cartilage. When, however, the explant was associated with soft connective tissue either as invading marrow or as an adjacent explant of synovium, the cartilage matrix was depleted of proteoglycan; IgG antibodies then entered the cartilage and reacted with the chondrocytes. After a lapse of 8-10 days, collagen also began to break down. If the degradation of collagen was not too extensive, the changes were reversible. Pure cartilage was depleted of proteoglycan by trypsinization and then cultivated in AS+C'. All the chondrocytes reacted with the IgG antibodies. The peripheral cells were killed, but those in the interior survived and rapidly secreted pericellular capsules rich in proteoglycan, which shielded them from further contact with antibodies. In other experiments, pure cartilage was associated with a synovial explant and cultivated in AS+C' for 10 days; this caused severe depletion of the matrix. The synovial tissue was then removed and the isolated cartilage cultured for a further 10 days in either AS+C' or control medium. If mainly proteoglycan had been lost during the primary culture period, breakdown did not continue in AS+C', and sometimes a little new matrix was regenerated, though less than in control medium; if, however, the collagen had been extensively degraded, breakdown continued even in control medium. It is suggested that in both the embryonic and post-foetal cartilage, degradation of the cartilage matrix was due to the enzymatic activity of the associated soft connective tissue which caused a loss first of proteoglycan, which enabled antibodies to reach the chondrocytes, and then of collagen. The possible relevance of these results to the pathogenesis of rheumatoid arthritis is discussed.", "contents": "Influence of the pericellular environment on the cells. The role of mucopolysaccharides in the protection of cartilage cells against immune reactions. Problems related to rheumatoid arthritis have been investigated by a group at Cambridge using the organ culture technique. Since auto-allergic reactions may be concerned in the chronicity of the disease, the effects of reactive complement-sufficient antisera (AS+C') on embryonic and post-foetal cartilage were examined. The cartilaginous limb bone rudiments enlarged to several times their original volume in control medium, but in the presence of AS+C' they gradually disintegrated, owing to the breakdown of the cartilage matrix; only the superficial cells of the enveloping soft connective tissue were killed, however. Provided breakdown had not advanced too far, the effects of AS+C' were reversible. It was not clear how AS+C' produced these changes, since cartilage matrix is impermeable to molecules as large as the immunoglobulins. To find whether there was a difference in permeability between embryonic and post-foetal cartilage, similar experiments were made on the articular cartilage of young pigs. AS+C' had no effect on pure articular cartilage, and it was shown immunohistochemically that IgG did not penetrate beyond the most superficial layer of cartilage. When, however, the explant was associated with soft connective tissue either as invading marrow or as an adjacent explant of synovium, the cartilage matrix was depleted of proteoglycan; IgG antibodies then entered the cartilage and reacted with the chondrocytes. After a lapse of 8-10 days, collagen also began to break down. If the degradation of collagen was not too extensive, the changes were reversible. Pure cartilage was depleted of proteoglycan by trypsinization and then cultivated in AS+C'. All the chondrocytes reacted with the IgG antibodies. The peripheral cells were killed, but those in the interior survived and rapidly secreted pericellular capsules rich in proteoglycan, which shielded them from further contact with antibodies. In other experiments, pure cartilage was associated with a synovial explant and cultivated in AS+C' for 10 days; this caused severe depletion of the matrix. The synovial tissue was then removed and the isolated cartilage cultured for a further 10 days in either AS+C' or control medium. If mainly proteoglycan had been lost during the primary culture period, breakdown did not continue in AS+C', and sometimes a little new matrix was regenerated, though less than in control medium; if, however, the collagen had been extensively degraded, breakdown continued even in control medium. It is suggested that in both the embryonic and post-foetal cartilage, degradation of the cartilage matrix was due to the enzymatic activity of the associated soft connective tissue which caused a loss first of proteoglycan, which enabled antibodies to reach the chondrocytes, and then of collagen. The possible relevance of these results to the pathogenesis of rheumatoid arthritis is discussed."}
{"id": "PMID:239427", "title": "The existence during gestation of an immunological buffer zone at the interface between maternal and foetal tissues.", "content": "In mammalian pregnancy the trophoblast normally constitutes an uninterrupted boundary of foetal tissue in immediate contact with maternal tissue, including blood in some species, and is the decisive immunological barrier to rejection of the foetus as an allograft. The ability of the trophoblast to function as a barrier evidently results from its capacity to resist immunological attack by either alloantibody or alloimmune cells and to prevent immunocompetent cells from reaching and damaging the foetus but, as yet, there is no general agreement regarding the means by which it exercises these functions. In view of the dramatic hormonal changes that occur during pregnancy and the undisputed involvement of trophoblast in these endocrine events, the possibility exists of an interaction between the hormones of pregnancy and the immunological phenomena. The present account furnishes evidence that endocrine activity at the maternal surface of the trophoblast, the presumptive site of the immunological frontier between foetus and mother, may be a factor in its local survival at implantation. The placental hormones so far known that are capable of blocking the antigen receptor sites of the mother's lymphocytes and thus preventing the latter from reacting with the foetal antigens are the glycoprotein, human chorionic gonadotrophin (HCG) and the polypeptide hormone, human chorionic somatomammotrophin (HCS) or human placental lactogen (HPL), both of which are specific to the human placenta. The origin of these hormones, their spatial distribution and their probable interaction with placental steroid hormones are discussed. It is argued that the place of highest concentration of these hormones is on the surface of the syncytial microvilli and the adjacent caviolae of the apical plasma membrane, as well as on the surfaces of the persisting cytotrophoblastic cells of the basal plate (cytotrophoblastic shell), the cell islands and the septa-precisely where the immunological challenge of the foetal allograft to the maternal host occurs. An explanation is offered for the continuing production of the voluminous quantities of these hormones during human pregnancy.", "contents": "The existence during gestation of an immunological buffer zone at the interface between maternal and foetal tissues. In mammalian pregnancy the trophoblast normally constitutes an uninterrupted boundary of foetal tissue in immediate contact with maternal tissue, including blood in some species, and is the decisive immunological barrier to rejection of the foetus as an allograft. The ability of the trophoblast to function as a barrier evidently results from its capacity to resist immunological attack by either alloantibody or alloimmune cells and to prevent immunocompetent cells from reaching and damaging the foetus but, as yet, there is no general agreement regarding the means by which it exercises these functions. In view of the dramatic hormonal changes that occur during pregnancy and the undisputed involvement of trophoblast in these endocrine events, the possibility exists of an interaction between the hormones of pregnancy and the immunological phenomena. The present account furnishes evidence that endocrine activity at the maternal surface of the trophoblast, the presumptive site of the immunological frontier between foetus and mother, may be a factor in its local survival at implantation. The placental hormones so far known that are capable of blocking the antigen receptor sites of the mother's lymphocytes and thus preventing the latter from reacting with the foetal antigens are the glycoprotein, human chorionic gonadotrophin (HCG) and the polypeptide hormone, human chorionic somatomammotrophin (HCS) or human placental lactogen (HPL), both of which are specific to the human placenta. The origin of these hormones, their spatial distribution and their probable interaction with placental steroid hormones are discussed. It is argued that the place of highest concentration of these hormones is on the surface of the syncytial microvilli and the adjacent caviolae of the apical plasma membrane, as well as on the surfaces of the persisting cytotrophoblastic cells of the basal plate (cytotrophoblastic shell), the cell islands and the septa-precisely where the immunological challenge of the foetal allograft to the maternal host occurs. An explanation is offered for the continuing production of the voluminous quantities of these hormones during human pregnancy."}
{"id": "PMID:239428", "title": "The relation between connective tissue cells and intercellular substances, including basement membranes.", "content": "Basement membranes are distributed widely in the body forming an extracellular matrix for epithelial and endothelial cells. The collagenous and glycoprotein constituents of basement membranes are synthesized by these two cell types. Disturbance of the interactions between basement membranes and their associated epithelial and endothelial cells can lead to the pathological changes seen in diseases involving basement membranes. These changes are illustrated here by reference to glomerulonephritis induced by the deposition of immune complexes in the glomerulus of the kidney, and chronic inflammatory changes occurring in the lung after inhalation of asbestos. In these diseases basement membrane changes can occur in several ways. Hydrolytic enzymes released from inflammatory cells degrade basement membranes while other constituents by epithelial and endothelial cells. Alternatively the physical separation of epithelial and endothelial cells from their basement membrances by space-occupying substances such as immune complexes can interfere with feedback mechanisms leading to synthesis of basement membrane constituents and cell proliferation. Studies of these pathological changes at a cellular level should shed new light on the ways in which cells interact with their pericellular environment.", "contents": "The relation between connective tissue cells and intercellular substances, including basement membranes. Basement membranes are distributed widely in the body forming an extracellular matrix for epithelial and endothelial cells. The collagenous and glycoprotein constituents of basement membranes are synthesized by these two cell types. Disturbance of the interactions between basement membranes and their associated epithelial and endothelial cells can lead to the pathological changes seen in diseases involving basement membranes. These changes are illustrated here by reference to glomerulonephritis induced by the deposition of immune complexes in the glomerulus of the kidney, and chronic inflammatory changes occurring in the lung after inhalation of asbestos. In these diseases basement membrane changes can occur in several ways. Hydrolytic enzymes released from inflammatory cells degrade basement membranes while other constituents by epithelial and endothelial cells. Alternatively the physical separation of epithelial and endothelial cells from their basement membrances by space-occupying substances such as immune complexes can interfere with feedback mechanisms leading to synthesis of basement membrane constituents and cell proliferation. Studies of these pathological changes at a cellular level should shed new light on the ways in which cells interact with their pericellular environment."}
{"id": "PMID:239429", "title": "A possible model for cell-cell recognition via surface macromolecules.", "content": "Alternative possibilities for the establishment of the proper cell distribution during embryogenesis are summarized at the beginning, followed by an assessment of the examples known so far where cell-cell recognition is known to be mediated via cell surface components. In the second part the species-specific recognition process which occurs during the sorting-out of dissociated sponge cells is analysed since it may serve as a possible model for cell-cell recognition in higher animals. Three possible mechanisms for the establishment of proper cell distribution are considered. These include, first, chemotaxis: secondly, guidance of cell or cell sheet  movement by extracellular matrix or by surrounding cells and thirdly, random movement followed by recognition at the final point of destination. Recognition is necessary for both of the two latter processes, i.e. for cell guidance as well as for locking the cells into their final position after random movement. Two basically different recognition mechanisms should be distinguished from each other. On the one hand cells may recognize each other with the help of macromolecules situated in or just outside of the plasmamembrane which fit to each other like enzymes and substrates or antibodies and antigens. On the other hand, cells may exchange information by exchanging cytoplasmatic components via vesicles or gap junctions. The species-specific aggregation of dissociated sponge cells is considered to be a possible model for cell-cell recognition in higher animals. A proteoglycan-like intercellular macromolecule called aggregation factor seems to mediate recognition of a given species of cells in the reaggregation process of dissociated cells. The data available at the present time suggest that a monovalent surface macromolecule (baseplate) may mediate the recognition process probably by recognizing the carbohydrate side chains of the multivalent proteoglycan aggregation factor. A cell-free system was devised to mimic this aggregation process. Addition of aggregation factor to baseplate-coated sepharose beads of approximately the size of the original sponge cells has essentially the same characteristics as the cellular system. Macromolecule-coded surface information for the recognition between cells has not been established during the embryogenesis of higher animals and remains an interesting challenge.", "contents": "A possible model for cell-cell recognition via surface macromolecules. Alternative possibilities for the establishment of the proper cell distribution during embryogenesis are summarized at the beginning, followed by an assessment of the examples known so far where cell-cell recognition is known to be mediated via cell surface components. In the second part the species-specific recognition process which occurs during the sorting-out of dissociated sponge cells is analysed since it may serve as a possible model for cell-cell recognition in higher animals. Three possible mechanisms for the establishment of proper cell distribution are considered. These include, first, chemotaxis: secondly, guidance of cell or cell sheet  movement by extracellular matrix or by surrounding cells and thirdly, random movement followed by recognition at the final point of destination. Recognition is necessary for both of the two latter processes, i.e. for cell guidance as well as for locking the cells into their final position after random movement. Two basically different recognition mechanisms should be distinguished from each other. On the one hand cells may recognize each other with the help of macromolecules situated in or just outside of the plasmamembrane which fit to each other like enzymes and substrates or antibodies and antigens. On the other hand, cells may exchange information by exchanging cytoplasmatic components via vesicles or gap junctions. The species-specific aggregation of dissociated sponge cells is considered to be a possible model for cell-cell recognition in higher animals. A proteoglycan-like intercellular macromolecule called aggregation factor seems to mediate recognition of a given species of cells in the reaggregation process of dissociated cells. The data available at the present time suggest that a monovalent surface macromolecule (baseplate) may mediate the recognition process probably by recognizing the carbohydrate side chains of the multivalent proteoglycan aggregation factor. A cell-free system was devised to mimic this aggregation process. Addition of aggregation factor to baseplate-coated sepharose beads of approximately the size of the original sponge cells has essentially the same characteristics as the cellular system. Macromolecule-coded surface information for the recognition between cells has not been established during the embryogenesis of higher animals and remains an interesting challenge."}
{"id": "PMID:239430", "title": "Role of the cell surface in selection during transport of proteins from mother to foetus and newly born.", "content": "The transport of immunoglobulins from mother to foetus and newly born mammal involves selective events which are independent of molecular size, related to immunoglobulin class, structure, and species of origin, and involve considerable protein degradation. Such events are briefly described as background information to a discussion of how selection of proteins might take place during transport across the cellular barriers concerned, namely the yolk sac splanchnopleur, chorio-allantoic placenta, and small intesting. Until recently the Brambell hypothesis has been the most favoured explanation. This implies that selection occurs intracellularly, within endodermal cells of the yolk sac splanchnopleur and small intestine, and within the syncytiotrophoblast of the chorio-allantoic placenta, of certain species. It also suggests that specific receptors are present which give attached proteins protection from degradation when the vesicles containing them fuse with lysosomes; such protected proteins are then liberated from the vesicle by exocytosis. This hypothesis is examined in the light of what is now known about the mechanism of uptake and transport of proteins by the endodermal cells and syncytiotrophoblast. It is suggested that rather than being an intracellular event, involving protection from proteolytic degradation, selection takes place at the cell surface. Evidence is presented, some direct and some circumstantial, that proteins may be selectively endocytosed by coated micropinocytotic vesicles, and non-selectively endocytosed through a complex apical canalicular system leading to macropinocytotic vesicle formation. In the small intesting of the suckling rat these two processes appear to be segregated, selective uptake occurring in the proximal half and non-selective uptake occurring in the distal half. In the endodermal cells of the rabbit yolk sac splanchnopleur, and by implication in the syncytiotrophoblast of man and monkey, it is suggested that both selective, and non-selective, uptake of protein occurs. Non-selective uptake into macropinocytotic vesicles is regarded as an event leading to complete degradation of all contained protein and functioning so as to supply the foetus and newly born mammal with essential amino acids. Selective uptake into coated micropinocytotic vesicles is regarded as an event leading to the transport of immunoglobulins across the cell without any contact with lysosomes, and functioning so as to supply the newly born mammal with protection against invasive organism. Specific receptors are still required but only for the initial uptake and segregation of proteins into coated micropinocytotic vesicles. The role which the glycocalyx might have in such selective binding of proteins is considered and possible difficulties in characterization of specific receptors brought to light in view of the likely overwhelming need for non-specific binding to effect non-selective uptake.", "contents": "Role of the cell surface in selection during transport of proteins from mother to foetus and newly born. The transport of immunoglobulins from mother to foetus and newly born mammal involves selective events which are independent of molecular size, related to immunoglobulin class, structure, and species of origin, and involve considerable protein degradation. Such events are briefly described as background information to a discussion of how selection of proteins might take place during transport across the cellular barriers concerned, namely the yolk sac splanchnopleur, chorio-allantoic placenta, and small intesting. Until recently the Brambell hypothesis has been the most favoured explanation. This implies that selection occurs intracellularly, within endodermal cells of the yolk sac splanchnopleur and small intestine, and within the syncytiotrophoblast of the chorio-allantoic placenta, of certain species. It also suggests that specific receptors are present which give attached proteins protection from degradation when the vesicles containing them fuse with lysosomes; such protected proteins are then liberated from the vesicle by exocytosis. This hypothesis is examined in the light of what is now known about the mechanism of uptake and transport of proteins by the endodermal cells and syncytiotrophoblast. It is suggested that rather than being an intracellular event, involving protection from proteolytic degradation, selection takes place at the cell surface. Evidence is presented, some direct and some circumstantial, that proteins may be selectively endocytosed by coated micropinocytotic vesicles, and non-selectively endocytosed through a complex apical canalicular system leading to macropinocytotic vesicle formation. In the small intesting of the suckling rat these two processes appear to be segregated, selective uptake occurring in the proximal half and non-selective uptake occurring in the distal half. In the endodermal cells of the rabbit yolk sac splanchnopleur, and by implication in the syncytiotrophoblast of man and monkey, it is suggested that both selective, and non-selective, uptake of protein occurs. Non-selective uptake into macropinocytotic vesicles is regarded as an event leading to complete degradation of all contained protein and functioning so as to supply the foetus and newly born mammal with essential amino acids. Selective uptake into coated micropinocytotic vesicles is regarded as an event leading to the transport of immunoglobulins across the cell without any contact with lysosomes, and functioning so as to supply the newly born mammal with protection against invasive organism. Specific receptors are still required but only for the initial uptake and segregation of proteins into coated micropinocytotic vesicles. The role which the glycocalyx might have in such selective binding of proteins is considered and possible difficulties in characterization of specific receptors brought to light in view of the likely overwhelming need for non-specific binding to effect non-selective uptake."}
{"id": "PMID:239431", "title": "Inhibition of adenosine 3',5'-monophosphate phosphodiesterase by nicotinamide and its homologues in vitro.", "content": "Inhibition of cAMP phosphodiesterase from rat liver by nicotinamide and its homologues was studied. Among the several compounds tested, such agents as nicotinamide, N2-ethylnicotinamide, N2-methylnicotinamide, N,N-diethylnicotinamide, 3-acetylpyridine, methylnicotinate, and ethylnicotinate showed potent inhibition of cAMP phosphodiesterase, with an over 90% inhibition by 5 mM ethylnicotinate when cAMP was used as substrate at a 0.48 x 10(-7) M concentration. A comparison of the inhibitory curves of theophylline, papaverine, and ethylnicotinate on enzyme activity showed them to be approximately coincident. Furthermore, the plots with abscissa of equal increments per concentration of ethylnicotinate in the presence of theophylline or papaverine coincided with that in the absence of these agents.", "contents": "Inhibition of adenosine 3',5'-monophosphate phosphodiesterase by nicotinamide and its homologues in vitro. Inhibition of cAMP phosphodiesterase from rat liver by nicotinamide and its homologues was studied. Among the several compounds tested, such agents as nicotinamide, N2-ethylnicotinamide, N2-methylnicotinamide, N,N-diethylnicotinamide, 3-acetylpyridine, methylnicotinate, and ethylnicotinate showed potent inhibition of cAMP phosphodiesterase, with an over 90% inhibition by 5 mM ethylnicotinate when cAMP was used as substrate at a 0.48 x 10(-7) M concentration. A comparison of the inhibitory curves of theophylline, papaverine, and ethylnicotinate on enzyme activity showed them to be approximately coincident. Furthermore, the plots with abscissa of equal increments per concentration of ethylnicotinate in the presence of theophylline or papaverine coincided with that in the absence of these agents."}
{"id": "PMID:239432", "title": "Fractures of the mandible. A review of 909 cases.", "content": "During a 5-year period, 909 fractures of the mandible were treated by the Department of Plastic Surgery at Groote Schuur Hospital in Cape Town. A simple technique based on Gilmer wiring was evolved to deal with those fractures where sufficient teeth were present. This technique is extremely simple and proved efficacious.", "contents": "Fractures of the mandible. A review of 909 cases. During a 5-year period, 909 fractures of the mandible were treated by the Department of Plastic Surgery at Groote Schuur Hospital in Cape Town. A simple technique based on Gilmer wiring was evolved to deal with those fractures where sufficient teeth were present. This technique is extremely simple and proved efficacious."}
{"id": "PMID:239441", "title": "Neurotransmitter content of mouse brain after inactivation by microwave heating.", "content": "Mice were sacrificed by either microwave inactivation of brain enzymes or by cervical dislocation. The norepinephrine, serotonin, 5-hydroxyindoleacetic acid and homovanillic acid content of the brains of the irradiated animals was significantly greater than that of the conventionally sacrificed controls.", "contents": "Neurotransmitter content of mouse brain after inactivation by microwave heating. Mice were sacrificed by either microwave inactivation of brain enzymes or by cervical dislocation. The norepinephrine, serotonin, 5-hydroxyindoleacetic acid and homovanillic acid content of the brains of the irradiated animals was significantly greater than that of the conventionally sacrificed controls."}
{"id": "PMID:239442", "title": "Benzodiazepine-induced suppression of estrous cycles in C57BL/6J mice.", "content": "Female C57BL/6J mice fed diets containing diazepam, chlordiazepoxide, oxazepam, prazepam, flurazepam, or nitrazepam exhibited significant decreases in the frequency of vaginal estrus.", "contents": "Benzodiazepine-induced suppression of estrous cycles in C57BL/6J mice. Female C57BL/6J mice fed diets containing diazepam, chlordiazepoxide, oxazepam, prazepam, flurazepam, or nitrazepam exhibited significant decreases in the frequency of vaginal estrus."}
{"id": "PMID:239443", "title": "A comparison of the inductive effects of phenobarbital, methaqualone, and methyprylon on hepatic mixed function oxidase enzymes in the rat.", "content": "The effects of equal doses of three sedative-hypnotics, phenobarbital, methaqualone, and methyprylon, on the hepatic mixed function oxidase enzymes of the rat were investigated and compared. After 5 days of pretreatment, phenobarbital and methyprylon significantly increased aminopyrine demethylation, aniline hydroxylation, and cytochrome P-450 content in hepatic microsomes. Methaqualone pretreatment only increased hepatic aminopyrine demethylase activity and wet liver weights. After 29 days of pretreatment, phenobarbital significantly increases aminopyrine demethylase, aniline hydroxylase activity, liver weight and cytochrome P-450 content. Methaqualone only produced a significant increase in wet liver weight.", "contents": "A comparison of the inductive effects of phenobarbital, methaqualone, and methyprylon on hepatic mixed function oxidase enzymes in the rat. The effects of equal doses of three sedative-hypnotics, phenobarbital, methaqualone, and methyprylon, on the hepatic mixed function oxidase enzymes of the rat were investigated and compared. After 5 days of pretreatment, phenobarbital and methyprylon significantly increased aminopyrine demethylation, aniline hydroxylation, and cytochrome P-450 content in hepatic microsomes. Methaqualone pretreatment only increased hepatic aminopyrine demethylase activity and wet liver weights. After 29 days of pretreatment, phenobarbital significantly increases aminopyrine demethylase, aniline hydroxylase activity, liver weight and cytochrome P-450 content. Methaqualone only produced a significant increase in wet liver weight."}
{"id": "PMID:239444", "title": "Binding of tritiated dehydroretronecine to macromolecules.", "content": "In vivo and in vitro experiments have shown that the pyrrolizidine alkaloid metabolite dehydroretronecine binds readily to macromolecules. In the in vivo experiment there was a preferential binding of dehydroretronecine to the gastric mucosa. Further extraction of the mucosa revealed a large percentage of the 3H was bound to the protein fraction and to a much lesser extent to DNA and RNA. The influence of pH on the binding of dehydroretronecine was substantiated in the in vitro experiment. Dehydroretronecine bound to calf thymus DNA and bovine serum albumin most readily under acidic conditions. These data suggest a direct correlation of the levels of dehydroretronecine binding to cellular macromolecules with the lesions that develop in affected organs.", "contents": "Binding of tritiated dehydroretronecine to macromolecules. In vivo and in vitro experiments have shown that the pyrrolizidine alkaloid metabolite dehydroretronecine binds readily to macromolecules. In the in vivo experiment there was a preferential binding of dehydroretronecine to the gastric mucosa. Further extraction of the mucosa revealed a large percentage of the 3H was bound to the protein fraction and to a much lesser extent to DNA and RNA. The influence of pH on the binding of dehydroretronecine was substantiated in the in vitro experiment. Dehydroretronecine bound to calf thymus DNA and bovine serum albumin most readily under acidic conditions. These data suggest a direct correlation of the levels of dehydroretronecine binding to cellular macromolecules with the lesions that develop in affected organs."}
{"id": "PMID:239445", "title": "Effect of cromolyn sodium and of daily exposure to compound 48/80 on experimental asthma.", "content": "Guinea pigs were exposed to aerosols of histamine or the mast cell degranulating and histamine releasing substance 48/80. Cromolyn sodium aerosols prevented 48/80 induced asthma but did not influence histamine induced broncho-constriction. 48/80 given daily for 5 days resulted in marked decrease in susceptibility to 48/80, possibly because of depletion of histamine and other active substances. There was no change in histamine sensitivity. After 3 days of rest, normal susceptibility to 48/80 returned.", "contents": "Effect of cromolyn sodium and of daily exposure to compound 48/80 on experimental asthma. Guinea pigs were exposed to aerosols of histamine or the mast cell degranulating and histamine releasing substance 48/80. Cromolyn sodium aerosols prevented 48/80 induced asthma but did not influence histamine induced broncho-constriction. 48/80 given daily for 5 days resulted in marked decrease in susceptibility to 48/80, possibly because of depletion of histamine and other active substances. There was no change in histamine sensitivity. After 3 days of rest, normal susceptibility to 48/80 returned."}
{"id": "PMID:239446", "title": "Some factors influencing colicin activity between pathogenic and commensal Escherichia coli from the pig.", "content": "Commensal strains of Escherichia coli derived from pigs had a broad spectrum of in vitro colicin acitivity against pathogenic serotypes. Of eight pathogenic serotypes tested, only three were colicinogenic and were active against relatively few commensal strains. Colicin activity was influenced by temperature, pH and oxygen tension as well as by the availability of certain nutrients and the presence of trypsin. Lack of colicin activity in intestinal supernatant fluid was ascribed to the concentration of trypsin present. It was concluded that colicins are unlikely to influence the dominance of pathogenic Escherichia coli serotypes in the pig's intestine, except possibly in the colon and rectum where the concentration of trypsin is low.", "contents": "Some factors influencing colicin activity between pathogenic and commensal Escherichia coli from the pig. Commensal strains of Escherichia coli derived from pigs had a broad spectrum of in vitro colicin acitivity against pathogenic serotypes. Of eight pathogenic serotypes tested, only three were colicinogenic and were active against relatively few commensal strains. Colicin activity was influenced by temperature, pH and oxygen tension as well as by the availability of certain nutrients and the presence of trypsin. Lack of colicin activity in intestinal supernatant fluid was ascribed to the concentration of trypsin present. It was concluded that colicins are unlikely to influence the dominance of pathogenic Escherichia coli serotypes in the pig's intestine, except possibly in the colon and rectum where the concentration of trypsin is low."}
{"id": "PMID:239447", "title": "Effect of carbacholine and urecholine on pentagastrin-stimulated gastric secretion in healthy subjects.", "content": "Dose-response studies of pentagastrin-stimulated gastric secretion were performed in 6 healthy volunteers. On different days pentagastrin was given in doses of 0.15, 1.5, and 15 mug/kg/hr either alone or in combination with carbacholine, 2 mug/kg/hr, or urecholine, 60 mug/kg/hr. Carbacholine and urecholine increased acid and pepsin secretion evoked by the lowest dose of pentagastrin while there was no augmentation at the highest dose. The dose of pentagastrin required to elicit half maximal acid output (Km) tended to decrease by simultaneous infusion of carbacholine or urecholine, suggesting that the cholinomimetics increased the sensitivity of the parietal cells to pentagastrin stimulation. Km for pentagastrin alone was higher than previously found in unoperated duodenal ulcer patients.", "contents": "Effect of carbacholine and urecholine on pentagastrin-stimulated gastric secretion in healthy subjects. Dose-response studies of pentagastrin-stimulated gastric secretion were performed in 6 healthy volunteers. On different days pentagastrin was given in doses of 0.15, 1.5, and 15 mug/kg/hr either alone or in combination with carbacholine, 2 mug/kg/hr, or urecholine, 60 mug/kg/hr. Carbacholine and urecholine increased acid and pepsin secretion evoked by the lowest dose of pentagastrin while there was no augmentation at the highest dose. The dose of pentagastrin required to elicit half maximal acid output (Km) tended to decrease by simultaneous infusion of carbacholine or urecholine, suggesting that the cholinomimetics increased the sensitivity of the parietal cells to pentagastrin stimulation. Km for pentagastrin alone was higher than previously found in unoperated duodenal ulcer patients."}
{"id": "PMID:239448", "title": "Gastro-oesophageal acid reflux. Method for 12-hour continuous recording of oesophageal pH with analysis of records.", "content": "Description of method for continuous recording of oesophageal pH and automatic, electronic analysis of records. Stability of apparatus has been tested over 12 hours in the laboratory with different buffer solutions and gastric secretions with and without bile, and on 36 patients with oesophageal disorders. Drift of apparatus max. 0.2 pH units. The analyser, dividing the pH range into arbitrary intervals, performs a rapid and reliable analysis of single examinations from variable criteria. The temporal distribution of pH values into the intervals is expressed in percentages of the total time of recording. Reliability of the analyser was tested by analysis of a simulated pH curve on which changes in amplitude corresponded to the most rapid changes seen in practice. Deviation below one per cent. Repeated analyses of the same records showed a coefficient of variation for the various analytical interval to be 10-0.01 per cent. The method allows recording of the number of reflux episodes, duration of each episode and total duration of pH within chosen limits.", "contents": "Gastro-oesophageal acid reflux. Method for 12-hour continuous recording of oesophageal pH with analysis of records. Description of method for continuous recording of oesophageal pH and automatic, electronic analysis of records. Stability of apparatus has been tested over 12 hours in the laboratory with different buffer solutions and gastric secretions with and without bile, and on 36 patients with oesophageal disorders. Drift of apparatus max. 0.2 pH units. The analyser, dividing the pH range into arbitrary intervals, performs a rapid and reliable analysis of single examinations from variable criteria. The temporal distribution of pH values into the intervals is expressed in percentages of the total time of recording. Reliability of the analyser was tested by analysis of a simulated pH curve on which changes in amplitude corresponded to the most rapid changes seen in practice. Deviation below one per cent. Repeated analyses of the same records showed a coefficient of variation for the various analytical interval to be 10-0.01 per cent. The method allows recording of the number of reflux episodes, duration of each episode and total duration of pH within chosen limits."}
{"id": "PMID:239449", "title": "The stability of human pepsins in stored gastric juice.", "content": "The effect of storage at -20 degrees C and +2 degrees C on the pepsins of human gastric juice was assessed by quantitative assay and agar gel electrophoresis. Quantitative assays showed no significant loss of peptic activity at either temperature over periods of storage up to 3 weeks, and no correlation between change in peptic activity and the acidity of the gastric juice, although raising the pH of the gastric juice above pH 2 with buffers gave improved stability over gastric juice mixed with buffer of lower pH. At low pH, the addition of bovine serum albumin gave improved stability. Agar gel electrophoresis showed that the pepsins were all stable at -20 degrees C for several days or several weeks, but alterations occurred in the pepsin molecules after several months.", "contents": "The stability of human pepsins in stored gastric juice. The effect of storage at -20 degrees C and +2 degrees C on the pepsins of human gastric juice was assessed by quantitative assay and agar gel electrophoresis. Quantitative assays showed no significant loss of peptic activity at either temperature over periods of storage up to 3 weeks, and no correlation between change in peptic activity and the acidity of the gastric juice, although raising the pH of the gastric juice above pH 2 with buffers gave improved stability over gastric juice mixed with buffer of lower pH. At low pH, the addition of bovine serum albumin gave improved stability. Agar gel electrophoresis showed that the pepsins were all stable at -20 degrees C for several days or several weeks, but alterations occurred in the pepsin molecules after several months."}
{"id": "PMID:239450", "title": "Hydrogen ion, pepsin and bile acid binding properties of hydrotalcite.", "content": "The hydrogen ion, pepsin and bile acid binding properties of hydrotalcite (Altacite) were investigated in human gastric juice both in vitro and in vivo. Hydrotalcite is an efficient antacid in vivo and between pH 2,5 and 3,5 it binds and inactivates pepsin in vitro. The results in one case suggest that this also occurs in vivo. Hydrotalcite is capable of removing substantial amounts of bile acids from bile-containing gastric juice in vivo. The findings indicate that hydrotalcite could be a useful agent in the treatment of both gastric and duodenal ulcers.", "contents": "Hydrogen ion, pepsin and bile acid binding properties of hydrotalcite. The hydrogen ion, pepsin and bile acid binding properties of hydrotalcite (Altacite) were investigated in human gastric juice both in vitro and in vivo. Hydrotalcite is an efficient antacid in vivo and between pH 2,5 and 3,5 it binds and inactivates pepsin in vitro. The results in one case suggest that this also occurs in vivo. Hydrotalcite is capable of removing substantial amounts of bile acids from bile-containing gastric juice in vivo. The findings indicate that hydrotalcite could be a useful agent in the treatment of both gastric and duodenal ulcers."}
{"id": "PMID:239451", "title": "Alfathesin for anaesthetic induction at caesarean section.", "content": "Anaesthesia was induced with Alfathesin (60 - 70 mul/kg) in 50 healthy mothers undergoing elective Caesarean section. Anaesthesia was maintained with nitrous oxide, oxygen, muscle relaxants and controlled ventilation. The mothers were tilted laterally throughout the operation. Blood gas studies done on the mothers before induction and at delivery, revealed a mild respiratory alkalosis associated with a moderate degree of metabolic acidosis, which appeared to increase during anaesthesia. Umbilical cord blood gas analyses indicated a mild degree of fetal respiratory acidosis (mean pCO2 Uv 45,3", "contents": "Alfathesin for anaesthetic induction at caesarean section. Anaesthesia was induced with Alfathesin (60 - 70 mul/kg) in 50 healthy mothers undergoing elective Caesarean section. Anaesthesia was maintained with nitrous oxide, oxygen, muscle relaxants and controlled ventilation. The mothers were tilted laterally throughout the operation. Blood gas studies done on the mothers before induction and at delivery, revealed a mild respiratory alkalosis associated with a moderate degree of metabolic acidosis, which appeared to increase during anaesthesia. Umbilical cord blood gas analyses indicated a mild degree of fetal respiratory acidosis (mean pCO2 Uv 45,3"}
{"id": "PMID:239452", "title": "Indications for intubation in laryngotracheobronchitis in black children.", "content": "Fifty-eight children with laryngotracheobronchitis (LTB) were studied. Many were malnourished, or in the post-measles state, or had some lower respiratory tract or cardiac involvement. In these patients, factors helpful in assessing the need for relief of airway obstruction by tracheal intubation have been evaluated. A set of indications for intubation, which includes clinical and arterial blood gas features of LTB is suggested. Cognisance of complications of disease, where present, has also been taken. If cyanosis or muscular hypotonia or unawareness is present, intubation is urgently needed. When two of the following occur together, the need for intubation has arisen: (a) pulse rate greater than 170/min and respiratory rate greater than 55/min; (b) paCO2 greater than 37 mmHg; (c) paO2 less than 50 mmHg; and (d) a complication (cardiac failure or severe lower respiratory tract infection).", "contents": "Indications for intubation in laryngotracheobronchitis in black children. Fifty-eight children with laryngotracheobronchitis (LTB) were studied. Many were malnourished, or in the post-measles state, or had some lower respiratory tract or cardiac involvement. In these patients, factors helpful in assessing the need for relief of airway obstruction by tracheal intubation have been evaluated. A set of indications for intubation, which includes clinical and arterial blood gas features of LTB is suggested. Cognisance of complications of disease, where present, has also been taken. If cyanosis or muscular hypotonia or unawareness is present, intubation is urgently needed. When two of the following occur together, the need for intubation has arisen: (a) pulse rate greater than 170/min and respiratory rate greater than 55/min; (b) paCO2 greater than 37 mmHg; (c) paO2 less than 50 mmHg; and (d) a complication (cardiac failure or severe lower respiratory tract infection)."}
{"id": "PMID:239454", "title": "Fanconi's syndrome in an adult.  A case history.", "content": "A case of the Fanconi syndrome in an adult presenting with life-threatening hypokalaemia is described.  Amino-aciduria, glycosuria, high phosphate and uric acid clearances with reduced plasma levels of these two substances, reduced urinary concentrating power and abnormal urinary potassium loss with a systemic acidosis, were the essential biochemical abnormalities.  Osteomalacia was shown by a radiological bone survey.", "contents": "Fanconi's syndrome in an adult.  A case history. A case of the Fanconi syndrome in an adult presenting with life-threatening hypokalaemia is described.  Amino-aciduria, glycosuria, high phosphate and uric acid clearances with reduced plasma levels of these two substances, reduced urinary concentrating power and abnormal urinary potassium loss with a systemic acidosis, were the essential biochemical abnormalities.  Osteomalacia was shown by a radiological bone survey."}
{"id": "PMID:239455", "title": "The respiratory effects of tilidine hydrochloride.", "content": "A standard 50-mg dose of tilidine hydrochloride (Valoron) was administered to 20 patients in the postoperative phase of open-heart surgery. No significant change in respiratory status, as measured by arterial blood gas analysis, was demonstrated with this dosage.", "contents": "The respiratory effects of tilidine hydrochloride. A standard 50-mg dose of tilidine hydrochloride (Valoron) was administered to 20 patients in the postoperative phase of open-heart surgery. No significant change in respiratory status, as measured by arterial blood gas analysis, was demonstrated with this dosage."}
{"id": "PMID:239456", "title": "Propanidid for anaesthetic induction at Caesarean section.", "content": "In 50 healthy mothers scheduled for elective Caesarean section, anaesthesia was induced with propanidid (7 mg/kg body weight). Thereafter, ventilation was controlled with nitrous oxide, oxygen and muscle relaxants. A further dose of propanidid (1 mg/kg body weight) was administered 3 minutes after the initial injection of this drug, as a means of preventing maternal awareness during equilibration with the anaesthetic gas mixture. The acid-base status of the mothers before the induction of anaesthesia, and at delivery, revealed a mild degree of respiratory alkalosis with a compensatory metabolic acidosis. Umbilical cord blood gas results indicated the presence of significant fetal acidosis, both respiratory (mean pCO2 Uv 46,3 torr (SD 11,3) and Ua 54,3 torr (SD 12,0)), and metabolic (mean base excess Uv-9 mEq/l (SD 4,2) and Ua-11,8 mEq/l, (SD 5,0)) in origin. The average umbilical cord blood oxygen tensions were Uv 25,9 torr (SD 10), and Ua 15,4 torr (SD 8,5); mean maternal to fetal base-excess gradients were Ma-Uv 4,1 mEq/l (SD 2,8) and Ma-Ua 6,5 mEq/l (SD 3,5). Five mothers (10%) offered convincing evidence of factual recall during surgery, and 3 of these were aware of pain. Nausea and vomiting occurred in 5 patients and in 4 there were clinical signs of postoperative chest infection. The degree of fetal biochemical asphyxia, and the incidence of maternal awareness during surgery, were significantly greater than previously reported when thiopentone was used for the induction of anaesthesia for Caesarean section. The results obtained are discussed, and the conclusion is drawn that propanidid for anaesthesia appears to offer no advantage over thiopentone in obstetric practice.", "contents": "Propanidid for anaesthetic induction at Caesarean section. In 50 healthy mothers scheduled for elective Caesarean section, anaesthesia was induced with propanidid (7 mg/kg body weight). Thereafter, ventilation was controlled with nitrous oxide, oxygen and muscle relaxants. A further dose of propanidid (1 mg/kg body weight) was administered 3 minutes after the initial injection of this drug, as a means of preventing maternal awareness during equilibration with the anaesthetic gas mixture. The acid-base status of the mothers before the induction of anaesthesia, and at delivery, revealed a mild degree of respiratory alkalosis with a compensatory metabolic acidosis. Umbilical cord blood gas results indicated the presence of significant fetal acidosis, both respiratory (mean pCO2 Uv 46,3 torr (SD 11,3) and Ua 54,3 torr (SD 12,0)), and metabolic (mean base excess Uv-9 mEq/l (SD 4,2) and Ua-11,8 mEq/l, (SD 5,0)) in origin. The average umbilical cord blood oxygen tensions were Uv 25,9 torr (SD 10), and Ua 15,4 torr (SD 8,5); mean maternal to fetal base-excess gradients were Ma-Uv 4,1 mEq/l (SD 2,8) and Ma-Ua 6,5 mEq/l (SD 3,5). Five mothers (10%) offered convincing evidence of factual recall during surgery, and 3 of these were aware of pain. Nausea and vomiting occurred in 5 patients and in 4 there were clinical signs of postoperative chest infection. The degree of fetal biochemical asphyxia, and the incidence of maternal awareness during surgery, were significantly greater than previously reported when thiopentone was used for the induction of anaesthesia for Caesarean section. The results obtained are discussed, and the conclusion is drawn that propanidid for anaesthesia appears to offer no advantage over thiopentone in obstetric practice."}
{"id": "PMID:239457", "title": "Hemodynamic effects of intra-arterial infusions of catecholamines on the canine gastric circulation.", "content": "The effects of intra-arterial infusions of epinephrine, norepinephrine, and isoproterenol upon right and left gastric blood flow were studied in anesthetized dogs. Blood flow was measured electromagnetically before and after adrenergic blockade. Infusion of epinephrine (0.05 mug Kg.(-1) min.(-1)) resulted in vasoconstriction (-50 +/- 6 ml. min.(-1)) with autoregulatory escape in the right gastric artery (RGA) and constriction (-41 +/- 8 ml. min.(-1)) followed by significant dilation (+ 56 +/- 10 ml. min.(-1)) in the left gastric artery (LGA). Alpha adrenergic blockade with phenoxybenzamine produced only a dilator response in both RGA and LGA to epinephrine infusion and beta adrenergic blockade resulted in a constrictor response with no autoregulatory escape. Norepinephrine infusions produced a constrictor response of similar magnitude as epinephrine but with little evidence of autoregulatory escape in either RGA and LGA. Alpha adrenergic blockade significantly attenuated this response in both circulations. Isoproterenol is a dilator in both circulations and its response is attenuated only by beta adrenergic blockade. This study demonstrates that the canine stomach has two regionally distinct circulations with the fundus and body exhibiting a greater dilator response than the antrum and pylorus.", "contents": "Hemodynamic effects of intra-arterial infusions of catecholamines on the canine gastric circulation. The effects of intra-arterial infusions of epinephrine, norepinephrine, and isoproterenol upon right and left gastric blood flow were studied in anesthetized dogs. Blood flow was measured electromagnetically before and after adrenergic blockade. Infusion of epinephrine (0.05 mug Kg.(-1) min.(-1)) resulted in vasoconstriction (-50 +/- 6 ml. min.(-1)) with autoregulatory escape in the right gastric artery (RGA) and constriction (-41 +/- 8 ml. min.(-1)) followed by significant dilation (+ 56 +/- 10 ml. min.(-1)) in the left gastric artery (LGA). Alpha adrenergic blockade with phenoxybenzamine produced only a dilator response in both RGA and LGA to epinephrine infusion and beta adrenergic blockade resulted in a constrictor response with no autoregulatory escape. Norepinephrine infusions produced a constrictor response of similar magnitude as epinephrine but with little evidence of autoregulatory escape in either RGA and LGA. Alpha adrenergic blockade significantly attenuated this response in both circulations. Isoproterenol is a dilator in both circulations and its response is attenuated only by beta adrenergic blockade. This study demonstrates that the canine stomach has two regionally distinct circulations with the fundus and body exhibiting a greater dilator response than the antrum and pylorus."}
{"id": "PMID:239458", "title": "Light scattering changes of edetic acid-treated, washed rat platelets: effect of adenosine diphosphate and calcium ion in relation to chilling.", "content": "The effe-ts of adenosine diphosphate (ADP) and Ca2+ on platelet morphology were studied in edetic acid (EDTA)-treated, washed platelets of rat by means of light scattering measurement at right angles. ADP caused a transient change of light scattering, which was independent of concentration above 5 muM and of pH between 4 and 10. When the platelets were pretreated with ADP or chilled persistently, Ca2+ also caused another transient change of light scattering. The effect of Ca2+ was abolsihed at pH below 6.5. The velocity of both ADP- and Ca2+-induced response was dependnet on temperature, and the magnitude was reduced by metabolic inhibitors and SH-blocking agents. Adenosine triphosphate (ATP) competitively inhibited the ADP-induced response, but not the Ca2+-induced one. The response to Ca2+ of the control and chilled platelets was compared by scanning electron microgram. Apparent similarity of the effect of chilling on membrane structure to that of ADP was suggested.", "contents": "Light scattering changes of edetic acid-treated, washed rat platelets: effect of adenosine diphosphate and calcium ion in relation to chilling. The effe-ts of adenosine diphosphate (ADP) and Ca2+ on platelet morphology were studied in edetic acid (EDTA)-treated, washed platelets of rat by means of light scattering measurement at right angles. ADP caused a transient change of light scattering, which was independent of concentration above 5 muM and of pH between 4 and 10. When the platelets were pretreated with ADP or chilled persistently, Ca2+ also caused another transient change of light scattering. The effect of Ca2+ was abolsihed at pH below 6.5. The velocity of both ADP- and Ca2+-induced response was dependnet on temperature, and the magnitude was reduced by metabolic inhibitors and SH-blocking agents. Adenosine triphosphate (ATP) competitively inhibited the ADP-induced response, but not the Ca2+-induced one. The response to Ca2+ of the control and chilled platelets was compared by scanning electron microgram. Apparent similarity of the effect of chilling on membrane structure to that of ADP was suggested."}
{"id": "PMID:239459", "title": "The effect of human platelets on lipolytic activity in plasma.", "content": "A method for assay of lipolytic activity in platelet-poor plasma (PPP), platelet-rich plasma (PRP) and washed human platelets is presented. The lipolytic activity in PRP was about twice the activity in PPP. A significant correlation between lipolysis in platelets and platelet number was established. Molar sodium chloride strongly inhibited lipolytic activity in platelets and a washing procedure did not significantly change the lipolysis. The results indicate that a lipoprotein lipase is bound to human platelets and may play a role in metabolism of triglyceride in platelets.", "contents": "The effect of human platelets on lipolytic activity in plasma. A method for assay of lipolytic activity in platelet-poor plasma (PPP), platelet-rich plasma (PRP) and washed human platelets is presented. The lipolytic activity in PRP was about twice the activity in PPP. A significant correlation between lipolysis in platelets and platelet number was established. Molar sodium chloride strongly inhibited lipolytic activity in platelets and a washing procedure did not significantly change the lipolysis. The results indicate that a lipoprotein lipase is bound to human platelets and may play a role in metabolism of triglyceride in platelets."}
{"id": "PMID:239460", "title": "The activation of human factor IX.", "content": "The activation of factor IX purified from human plasma has been studied. Factor XIa and kallikrein separately activated factor IX to factor IXa. In both cases factor IXa had an apparent molecular wight of about 42-45000 in sodium dodecyl sulphate-polyacrylamide disc gel electrophoresis compared with a molecular weight of about 70000 for the native factor IX. The activation by XIa required Ca2+-ions, wherease Ca2+-in and factor VII or Russell's-viper venom alone did not activate factor IX. Trypsin activated and plasmin inactivated factor IX.", "contents": "The activation of human factor IX. The activation of factor IX purified from human plasma has been studied. Factor XIa and kallikrein separately activated factor IX to factor IXa. In both cases factor IXa had an apparent molecular wight of about 42-45000 in sodium dodecyl sulphate-polyacrylamide disc gel electrophoresis compared with a molecular weight of about 70000 for the native factor IX. The activation by XIa required Ca2+-ions, wherease Ca2+-in and factor VII or Russell's-viper venom alone did not activate factor IX. Trypsin activated and plasmin inactivated factor IX."}
{"id": "PMID:239468", "title": "Studies on stereospecific reduction of acetoacetyl CoA and crotonyl CoA in lactating rabbit mammary glands.", "content": "Stereospecificity as well as the dependency on reduced pyridine nucleotides of the enzymatic reduction of acetoacetyl CoA and crotonyl CoA in lactating rabbit mammary glands are reported. In the reduction of both acetoacetyl CoA and crotonyl CoA as substrates the tritium from NADP3H was stereospecifically incorporated into the beta-position of n-butyric acid. The reaction of acetoacetyl CoA reduction was much more dependent on NADH while the reduction of crotonyl CoA was rather more dependent on NADPH. There was no difference between the dependencies on NADH and NADPH in the reduction of 2-hexenyl CoA.", "contents": "Studies on stereospecific reduction of acetoacetyl CoA and crotonyl CoA in lactating rabbit mammary glands. Stereospecificity as well as the dependency on reduced pyridine nucleotides of the enzymatic reduction of acetoacetyl CoA and crotonyl CoA in lactating rabbit mammary glands are reported. In the reduction of both acetoacetyl CoA and crotonyl CoA as substrates the tritium from NADP3H was stereospecifically incorporated into the beta-position of n-butyric acid. The reaction of acetoacetyl CoA reduction was much more dependent on NADH while the reduction of crotonyl CoA was rather more dependent on NADPH. There was no difference between the dependencies on NADH and NADPH in the reduction of 2-hexenyl CoA."}
{"id": "PMID:239470", "title": "Radiation effects on rat testes. VIII. Kinetic properties of hydrolases following partial body gamma irradiation of rats.", "content": "Kinetic properties such as Michaelis constant (Km), maximum velocity (Vmax), temperature coefficient (Q10) and energy of activation (Ea) for hydrolysis of adenosine-5'-phosphate at pH 9.5 and sodium pyrophosphate at pH 8.35 by normal and radiated testes supernatants have been described. Kinetic parameters are related to respective phosphohydrolases (phosphatases). (1) Km values for 5'nucleotidase and inorganic pyrophosphatase of normal testis were determined as 1.25 X 10(-3)M and 0.81 X 10(-3)M respectively; (II) Vmax correspond to 318 mug P/15 min and 430 mug P/15 min for 100 mg tissue respectively; (III) Q10 for 5 nucleotidase is 1.7 and for inorganic pyrophosphatase is 4.2 at a temperature 10-30degreesC; (IV) Ea for hydrolysis of AMP and sodium pyrophosphate were calculated by Arrhenius plots as 17000 and 9000 cal/mol. (V) Km values for irradiated enzymes are similar to the control values suggesting that the binding capacities of these enzymes with their substrates remain unaffected after radiation; (VI) Vmax for radiated enzymes correspond to a value of 500 mug P/100 mg tissue/15 min for 5'nucleotidase and 118 mug P/100 mug tissue/15 min for inorganic pyrophosphatase; (VII) 110 for 5'nucleotidase is 2.2 and inorganic pyrophosphatase 1.16 at 10-30degreesC; (VIII) Ea for irradiated 5'nucleotidase is comparable to those of normal rats whereas for inorganic pyrophosphatase Ea is moderately declined. The observed changes have been related to the different types of metabolic activity in germinal and nongerminal cells of testes.", "contents": "Radiation effects on rat testes. VIII. Kinetic properties of hydrolases following partial body gamma irradiation of rats. Kinetic properties such as Michaelis constant (Km), maximum velocity (Vmax), temperature coefficient (Q10) and energy of activation (Ea) for hydrolysis of adenosine-5'-phosphate at pH 9.5 and sodium pyrophosphate at pH 8.35 by normal and radiated testes supernatants have been described. Kinetic parameters are related to respective phosphohydrolases (phosphatases). (1) Km values for 5'nucleotidase and inorganic pyrophosphatase of normal testis were determined as 1.25 X 10(-3)M and 0.81 X 10(-3)M respectively; (II) Vmax correspond to 318 mug P/15 min and 430 mug P/15 min for 100 mg tissue respectively; (III) Q10 for 5 nucleotidase is 1.7 and for inorganic pyrophosphatase is 4.2 at a temperature 10-30degreesC; (IV) Ea for hydrolysis of AMP and sodium pyrophosphate were calculated by Arrhenius plots as 17000 and 9000 cal/mol. (V) Km values for irradiated enzymes are similar to the control values suggesting that the binding capacities of these enzymes with their substrates remain unaffected after radiation; (VI) Vmax for radiated enzymes correspond to a value of 500 mug P/100 mg tissue/15 min for 5'nucleotidase and 118 mug P/100 mug tissue/15 min for inorganic pyrophosphatase; (VII) 110 for 5'nucleotidase is 2.2 and inorganic pyrophosphatase 1.16 at 10-30degreesC; (VIII) Ea for irradiated 5'nucleotidase is comparable to those of normal rats whereas for inorganic pyrophosphatase Ea is moderately declined. The observed changes have been related to the different types of metabolic activity in germinal and nongerminal cells of testes."}
{"id": "PMID:239473", "title": "Long-term survival of cardiac allografts in lethally irradiated rats repopulated with host-type hemopoietic cells.", "content": "To test the hypothesis that hemopoietic cells within a tissue graft are responsible for its immunogenicity, two experimental protocols were followed. LEW hearts were grafted into (LEW X BN)F-1 host rats and LEW or F-1 lymphocytes were injected into the apex of the grafted heart. The LEW but not the F-1 cells induced a local reaction, apparently because the circulating F-1 cells were the necessary immunogens. The second protocol took advantage of the knowledge that lethally irradiated LEW rats were able to reject WF Ag-B-incompatible hemopoietic cells (but not tissue allografts) within a few days. LEW rats were lethally irradiated and grafted with WF hearts on day 0. A mixture of LEW marrow, thymus, spleen and lymph node cells, or marrow cells only were infused either on day 0 or day 2. Cardiac allografts in hosts repopulated with the mixture of lymphoid cells survived a mean of 11.3 days in hosts infused on day 0, but survived indefinitely if the lymphoid cells were infused on day 2. The 2-day interval also prolonged the survival of allografts in rats infused with only marrow cells. The long-term recipients, without any further treatment, rejected WF skin grafts as first-set reactions 1 year later but did not reject second WF cardiac allografts. Lymphoid cells from long-term recipients imparied the rejection of WF cardiac allografts by LEW host rats. The lack of rejection of the original cardiac allograft supported the hypothesis tested. Certain hemopoietic cells responsible for the immunogenicity of cardiac allografts were probably eliminated in the 2-day interval at least in part by host effector cells capable of rejecting allogeneic hemopoietic cells. However, the mechanism of long-term \"unresponsiveness\" to WF hearts could have been caused by loss of accessory cells during the 2-day interval followed by infusion of immunocompetent cells. Skin rejections in these recipients may have been attributable to reactions against skin differentiation-specific antigens.", "contents": "Long-term survival of cardiac allografts in lethally irradiated rats repopulated with host-type hemopoietic cells. To test the hypothesis that hemopoietic cells within a tissue graft are responsible for its immunogenicity, two experimental protocols were followed. LEW hearts were grafted into (LEW X BN)F-1 host rats and LEW or F-1 lymphocytes were injected into the apex of the grafted heart. The LEW but not the F-1 cells induced a local reaction, apparently because the circulating F-1 cells were the necessary immunogens. The second protocol took advantage of the knowledge that lethally irradiated LEW rats were able to reject WF Ag-B-incompatible hemopoietic cells (but not tissue allografts) within a few days. LEW rats were lethally irradiated and grafted with WF hearts on day 0. A mixture of LEW marrow, thymus, spleen and lymph node cells, or marrow cells only were infused either on day 0 or day 2. Cardiac allografts in hosts repopulated with the mixture of lymphoid cells survived a mean of 11.3 days in hosts infused on day 0, but survived indefinitely if the lymphoid cells were infused on day 2. The 2-day interval also prolonged the survival of allografts in rats infused with only marrow cells. The long-term recipients, without any further treatment, rejected WF skin grafts as first-set reactions 1 year later but did not reject second WF cardiac allografts. Lymphoid cells from long-term recipients imparied the rejection of WF cardiac allografts by LEW host rats. The lack of rejection of the original cardiac allograft supported the hypothesis tested. Certain hemopoietic cells responsible for the immunogenicity of cardiac allografts were probably eliminated in the 2-day interval at least in part by host effector cells capable of rejecting allogeneic hemopoietic cells. However, the mechanism of long-term \"unresponsiveness\" to WF hearts could have been caused by loss of accessory cells during the 2-day interval followed by infusion of immunocompetent cells. Skin rejections in these recipients may have been attributable to reactions against skin differentiation-specific antigens."}
{"id": "PMID:239471", "title": "The role of the peripheral sympathetic nervous system in cerebral blood flow autoregulation.", "content": "The effect of chronic, unilateral superior cervical ganglionectomy on cerebral blood flow and blood flow autoregulaiton to changes in perfusion pressure was examined in seven phencyclidine anesthetized monkeys. Ten to 14 days prior to the experiments Doppler ultrasonic flow transducers were placed on both carotid arteries after ligation of the external carotid branches and removal of one superior cervical ganglion. Autoregulation was tested by exsanguination and metaraminol infusion with the monkeys inspiring from air, 9% and 12% carbon dioxide in air. Immediately following experimentation the cerebral vessels were examined for the presence of noradrenergic fibers. The results of the study demonstrate that: (1) superior cervical ganglionectomy produces a significant reduction in the noradrenergic innervation of ipsilateral extraparenchymal arteries: (2) the peripheral sympathetic nervous system contrivutes to overall cerebral vascular resistance primarily by affecting resistance in extraparenchymal arteries; and (3) as a result, it determines the contribution of the extraparenchymal arteries to overall cerebral blood flow autoregulation.", "contents": "The role of the peripheral sympathetic nervous system in cerebral blood flow autoregulation. The effect of chronic, unilateral superior cervical ganglionectomy on cerebral blood flow and blood flow autoregulaiton to changes in perfusion pressure was examined in seven phencyclidine anesthetized monkeys. Ten to 14 days prior to the experiments Doppler ultrasonic flow transducers were placed on both carotid arteries after ligation of the external carotid branches and removal of one superior cervical ganglion. Autoregulation was tested by exsanguination and metaraminol infusion with the monkeys inspiring from air, 9% and 12% carbon dioxide in air. Immediately following experimentation the cerebral vessels were examined for the presence of noradrenergic fibers. The results of the study demonstrate that: (1) superior cervical ganglionectomy produces a significant reduction in the noradrenergic innervation of ipsilateral extraparenchymal arteries: (2) the peripheral sympathetic nervous system contrivutes to overall cerebral vascular resistance primarily by affecting resistance in extraparenchymal arteries; and (3) as a result, it determines the contribution of the extraparenchymal arteries to overall cerebral blood flow autoregulation."}
{"id": "PMID:239474", "title": "Purification and characterization of guinea pig lymphotoxin produced by lymph node cells stimulated by phytohemagglutinin.", "content": "Guinea pig lymphotoxin (LT) produced by stimulation of lymph node cells with Phaseolus vulgaris phytohemagglutinin was purified approximately 1,000-fold in specific activity by ammonium sulfate fractionation, DEAE-Sephadex column chromatography, and gel filtration on Sephadex G-100. The properties of LT tested at the various stages of purification revealed that the LT was a heat-sensitive, protease-sensitive proteinaceous substance, and its approximate molecular weight was estimated to be 50,000 by means of gel filtration. The most purified fraction (Fr. D) was found to be devoid of the activities of migration inhibitory and mitogenic factors, clearly indicating that these activities are mediated by different substances.", "contents": "Purification and characterization of guinea pig lymphotoxin produced by lymph node cells stimulated by phytohemagglutinin. Guinea pig lymphotoxin (LT) produced by stimulation of lymph node cells with Phaseolus vulgaris phytohemagglutinin was purified approximately 1,000-fold in specific activity by ammonium sulfate fractionation, DEAE-Sephadex column chromatography, and gel filtration on Sephadex G-100. The properties of LT tested at the various stages of purification revealed that the LT was a heat-sensitive, protease-sensitive proteinaceous substance, and its approximate molecular weight was estimated to be 50,000 by means of gel filtration. The most purified fraction (Fr. D) was found to be devoid of the activities of migration inhibitory and mitogenic factors, clearly indicating that these activities are mediated by different substances."}
{"id": "PMID:239475", "title": "Depression of cellular immune response during syngeneic pregnancy as measured by the graft-versus-host reaction.", "content": "The cellular immune response during the course of intrastrain pregnancies was evaluated in primiparous and multiparous BALB/c females by the graft-versus-host (GVH) activity of the splenic and lymph nodal lymphocytes. Splenic lymphocytes of both primiparous and multiparous pregnant mice had a GVH activity lower than that of the virgin mice. This immune deficit was more evident in multiparous than in primiparous females and occurred at the 6th day and during the last week of pregnancy. A similar although less pronounced phenomenon was found when lymph nodes instead of spleen of multiparous females were used at the source of cells in GVH reaction. The immune deficit was less marked when spleen and lymph node cells of pregnant mice were compared with similar cells of pseudopregnant females. Incubation of virgin BALB/c spleen lymphocytes in the serum of multiparous pregnant mice as compared to normal virgin serum caused a reduction of the GVH activity; incubation of the cells in pseudopregnant serum also inhibited the immune response, but to a lesser extent than the incubation in multiparous sera.", "contents": "Depression of cellular immune response during syngeneic pregnancy as measured by the graft-versus-host reaction. The cellular immune response during the course of intrastrain pregnancies was evaluated in primiparous and multiparous BALB/c females by the graft-versus-host (GVH) activity of the splenic and lymph nodal lymphocytes. Splenic lymphocytes of both primiparous and multiparous pregnant mice had a GVH activity lower than that of the virgin mice. This immune deficit was more evident in multiparous than in primiparous females and occurred at the 6th day and during the last week of pregnancy. A similar although less pronounced phenomenon was found when lymph nodes instead of spleen of multiparous females were used at the source of cells in GVH reaction. The immune deficit was less marked when spleen and lymph node cells of pregnant mice were compared with similar cells of pseudopregnant females. Incubation of virgin BALB/c spleen lymphocytes in the serum of multiparous pregnant mice as compared to normal virgin serum caused a reduction of the GVH activity; incubation of the cells in pseudopregnant serum also inhibited the immune response, but to a lesser extent than the incubation in multiparous sera."}
{"id": "PMID:239472", "title": "Pial microcirculation in subarachnoid hemorrhage.", "content": "Microsurgical and microscopic methods were employed in guinea pigs to expose, observe, and measure response characteristics of cerebral cortical pial microvessels and microcirculation to traumatic and nontraumatic experimental subarachnoid hemorrhage. Bleeding produced by vascular micropuncture was associated with a 44.3% arteriolar constriction. Topical application of homologous blood alone produced a 33.2% vasoconstriction. Observed microcirculatory flow characteristics subsequent to such microvascular changes were consistent with those known to be associated with cerebral cortical infarction. These changes could be prevented or reversed by topical application of the alpha adrenergic blocker, phenoxybenzamine. Topical pretreatment with the beta adrenergic blocker, propranolol, prevented blood-induced spasm, but did not reverse such spasm once it had been established. A chemo-mechanical mechanism is suggested as underlying the vasoconstriction association with rupture of pial microvessels. It is thought that consideration of such microvascular characteristics, in conjunction with those known to be associated with larger intracranial vessels, adds to current knowledge of the pathophysiology of subarachnoid hemorrhage and may be extrapolated to bear future clinical import.", "contents": "Pial microcirculation in subarachnoid hemorrhage. Microsurgical and microscopic methods were employed in guinea pigs to expose, observe, and measure response characteristics of cerebral cortical pial microvessels and microcirculation to traumatic and nontraumatic experimental subarachnoid hemorrhage. Bleeding produced by vascular micropuncture was associated with a 44.3% arteriolar constriction. Topical application of homologous blood alone produced a 33.2% vasoconstriction. Observed microcirculatory flow characteristics subsequent to such microvascular changes were consistent with those known to be associated with cerebral cortical infarction. These changes could be prevented or reversed by topical application of the alpha adrenergic blocker, phenoxybenzamine. Topical pretreatment with the beta adrenergic blocker, propranolol, prevented blood-induced spasm, but did not reverse such spasm once it had been established. A chemo-mechanical mechanism is suggested as underlying the vasoconstriction association with rupture of pial microvessels. It is thought that consideration of such microvascular characteristics, in conjunction with those known to be associated with larger intracranial vessels, adds to current knowledge of the pathophysiology of subarachnoid hemorrhage and may be extrapolated to bear future clinical import."}
{"id": "PMID:239480", "title": "The case against a viral aetiology in feline urolithiasis.", "content": "Efforts have been made to endorse the thory of a viral aetiology for the feline urolithiasis syndrome (FUS) in the male cat. The presence of virus in the urine of three cases could not be confirned nor could the condition be transmitted by intra vesicular inoculation of urine from four affected cats into the bladders of normal cats. Following these negative findings work was done on SPF cats and a survey made of the incidence of urethral obstruction in six SPF cat units in England. No cases were reported from four of these units over a two-year period. Five cases occurred in the other two SPF units, three of which were associated with feeding an expanded dry cat food. There is, thus, no direct evidence that viral agents are involved in the aetiology of FUS.", "contents": "The case against a viral aetiology in feline urolithiasis. Efforts have been made to endorse the thory of a viral aetiology for the feline urolithiasis syndrome (FUS) in the male cat. The presence of virus in the urine of three cases could not be confirned nor could the condition be transmitted by intra vesicular inoculation of urine from four affected cats into the bladders of normal cats. Following these negative findings work was done on SPF cats and a survey made of the incidence of urethral obstruction in six SPF cat units in England. No cases were reported from four of these units over a two-year period. Five cases occurred in the other two SPF units, three of which were associated with feeding an expanded dry cat food. There is, thus, no direct evidence that viral agents are involved in the aetiology of FUS."}
{"id": "PMID:239485", "title": "The effects of sulphydryl reagents on the binding and mixed function oxidation of hexobarbital in rat hepatic microsomes.", "content": "1. The effects of the sulphydryl reagents p-chloromercuribenzoate, N-ethylmaleimide and iodoacetamide on the binding spectrum, oxygen consumption and formation of a suspected substrate-cytochrome P-450-oxygen complex for hexobarbital in rat liver microsomes were investigated. 2. The oxygen consumption caused by hexobarbital oxidation was inhibited non-competitively by all three agents, with 50% inhibition at 4 times 10(-5) M for p-chloromercuribenzoate, 3-7 times 10(-4) M for N-ethylmaleimide and 1-9 times 10(-3) M for iodoacetamide. Cysteamine protected and at least partially reversed this inhibition. 3. p-chloromercuribenzoate inhibited the formation of the cytochrome P-450-substrate-oxygen complex, while N-ethylmaleimide and iodoacetamide also inhibited the formation of this complex but to a lesser extent. The p-chloromercuribenzoate inhibition was protected against and reversed by cysteamine. 4. p-Chloromercuribenzoate and N-ethylmaleimide caused a 50% reduction in the magnitude of the hexobarbital-induced binding spectrum, and this was paralleled by the conversion of cytochrome P-450 to cytochrome P-420. Cysteamine protected against this effect but could not reverse it. Iodoacetamide had no effect on the binding spectrum of hexobarbital and failed to convert cytochrome P-450 to cytochrome P-420. 5. Points of attack within the reaction sequence of drug oxidation are tentatively ascribed to the sulphydryl reagents used in this study.", "contents": "The effects of sulphydryl reagents on the binding and mixed function oxidation of hexobarbital in rat hepatic microsomes. 1. The effects of the sulphydryl reagents p-chloromercuribenzoate, N-ethylmaleimide and iodoacetamide on the binding spectrum, oxygen consumption and formation of a suspected substrate-cytochrome P-450-oxygen complex for hexobarbital in rat liver microsomes were investigated. 2. The oxygen consumption caused by hexobarbital oxidation was inhibited non-competitively by all three agents, with 50% inhibition at 4 times 10(-5) M for p-chloromercuribenzoate, 3-7 times 10(-4) M for N-ethylmaleimide and 1-9 times 10(-3) M for iodoacetamide. Cysteamine protected and at least partially reversed this inhibition. 3. p-chloromercuribenzoate inhibited the formation of the cytochrome P-450-substrate-oxygen complex, while N-ethylmaleimide and iodoacetamide also inhibited the formation of this complex but to a lesser extent. The p-chloromercuribenzoate inhibition was protected against and reversed by cysteamine. 4. p-Chloromercuribenzoate and N-ethylmaleimide caused a 50% reduction in the magnitude of the hexobarbital-induced binding spectrum, and this was paralleled by the conversion of cytochrome P-450 to cytochrome P-420. Cysteamine protected against this effect but could not reverse it. Iodoacetamide had no effect on the binding spectrum of hexobarbital and failed to convert cytochrome P-450 to cytochrome P-420. 5. Points of attack within the reaction sequence of drug oxidation are tentatively ascribed to the sulphydryl reagents used in this study."}
{"id": "PMID:239486", "title": "Enzymic reduction of aromatic hydrocarbon epoxides by the microsomal fraction of rat liver.", "content": "1. The oxidation of aromatic hydrocarbons to arene oxides and the reduction of these oxides to the parent hydrocarbons are both catalysed by enzymes in the microsomal fraction of rat liver. A suggested name for the enzyme concerned in the reduction of these epoxides is 'epoxide reductase'. 2. 'Epoxide reductase' is NADPH-dependent and is inhibited by oxygen. 3. Preliminary investigations suggest that the enzyme is specific for both 'K-region' and 'non-K-region' arene oxides.", "contents": "Enzymic reduction of aromatic hydrocarbon epoxides by the microsomal fraction of rat liver. 1. The oxidation of aromatic hydrocarbons to arene oxides and the reduction of these oxides to the parent hydrocarbons are both catalysed by enzymes in the microsomal fraction of rat liver. A suggested name for the enzyme concerned in the reduction of these epoxides is 'epoxide reductase'. 2. 'Epoxide reductase' is NADPH-dependent and is inhibited by oxygen. 3. Preliminary investigations suggest that the enzyme is specific for both 'K-region' and 'non-K-region' arene oxides."}
{"id": "PMID:239487", "title": "Electron transport systems of lung microsomes and their physiological functions. Enzymic hydroxylation of aniline and steroids.", "content": "1. The hydroxylation of aniline by rabbit lung microsomes to rho-aminophenol required oxygen and NADPH, and was inhibited by menadione, ferricytochrome c and carbon monoxide. 2. NADH was a less effective electron donor than NADPH in this reaction, but its addition significantly increased the yield of rho-aminophenol formed in the presence of NADPH. 3. 4,16-Androstadien-3-one and 3beta-hydroxy-5-androsten-17-one were also metabolized by lung microsomes to the same products as are formed by hepatic microsomes.", "contents": "Electron transport systems of lung microsomes and their physiological functions. Enzymic hydroxylation of aniline and steroids. 1. The hydroxylation of aniline by rabbit lung microsomes to rho-aminophenol required oxygen and NADPH, and was inhibited by menadione, ferricytochrome c and carbon monoxide. 2. NADH was a less effective electron donor than NADPH in this reaction, but its addition significantly increased the yield of rho-aminophenol formed in the presence of NADPH. 3. 4,16-Androstadien-3-one and 3beta-hydroxy-5-androsten-17-one were also metabolized by lung microsomes to the same products as are formed by hepatic microsomes."}
{"id": "PMID:239483", "title": "[Effect of the characteristics of various alimentary stimuli and changes in the pH of the duodenal content on the acid-forming function of the stomach].", "content": "In chronic experiments on dogs the effect of introduction of a non-buffered acid gastric juice into the duodenum or/and of drawing outside the bile via a fistula in the common bile duct on theproduction of hydrochloric acid in innervated ventricles (pouches) was studied. The induced pH shifts in the duodenum were checked every 15 minutes in the duodenal chyme samples. In tests involving meat feeding the reduced pH of the duodenal contents acted not only as an inhibitor of the gastric secretion, but much more as its stimulator. Infusion of the juice into the duodenum, or/and elimination of the bile tended to drastically reduce the inhibitory effect of the fat on the acid-formation in the stomach, this being due to inactivation of the pancreated lipase with HCl and to a defective micellar stage of the intraintestinal transformation of fat. This gives ground to assume that the entrance of acid non-buffered gastric juice into the intestine during transtubal feeding of patients with peptic ulcer is counter-productive in this method of treatment. The application of hyposecretory agents concurrent with the tubal feeding is warranted.", "contents": "[Effect of the characteristics of various alimentary stimuli and changes in the pH of the duodenal content on the acid-forming function of the stomach]. In chronic experiments on dogs the effect of introduction of a non-buffered acid gastric juice into the duodenum or/and of drawing outside the bile via a fistula in the common bile duct on theproduction of hydrochloric acid in innervated ventricles (pouches) was studied. The induced pH shifts in the duodenum were checked every 15 minutes in the duodenal chyme samples. In tests involving meat feeding the reduced pH of the duodenal contents acted not only as an inhibitor of the gastric secretion, but much more as its stimulator. Infusion of the juice into the duodenum, or/and elimination of the bile tended to drastically reduce the inhibitory effect of the fat on the acid-formation in the stomach, this being due to inactivation of the pancreated lipase with HCl and to a defective micellar stage of the intraintestinal transformation of fat. This gives ground to assume that the entrance of acid non-buffered gastric juice into the intestine during transtubal feeding of patients with peptic ulcer is counter-productive in this method of treatment. The application of hyposecretory agents concurrent with the tubal feeding is warranted."}
{"id": "PMID:239488", "title": "The partial purification and properties of a human erythrocyte 4-nitroacetophenone reductase.", "content": "1. A soluble enzyme which catalyses the NADPH-dependent reduction of 4-nitroacetophenone to 4-nitrophenylmethylcarbinol has been partially purified from human erythrocytes. 2.inter-individual or intra-individual differences in the enzymic activity were small except for very low activity observed in one subject with glucose 6-phosphate dehydrogenase deficiency resulting in decreased levels of NADPH. 3. The enzyme was inactivated above 50 degrees or on storage at 4 degrees for longer than 24 h. The pH optimum was between 7-0-8-0. 4. the enzyme has been differentiated from NADPH-methaemoglobin reductase, NADPH-cytochrome c reductase, glutathione reductase, alpha,beta-unsaturated ketone reductase and aromatic alpha-keto acid reductase activities, but similarities exist between this enzyme and a rabbit kidney cortex aromatic aldehyde/ketone reductase.", "contents": "The partial purification and properties of a human erythrocyte 4-nitroacetophenone reductase. 1. A soluble enzyme which catalyses the NADPH-dependent reduction of 4-nitroacetophenone to 4-nitrophenylmethylcarbinol has been partially purified from human erythrocytes. 2.inter-individual or intra-individual differences in the enzymic activity were small except for very low activity observed in one subject with glucose 6-phosphate dehydrogenase deficiency resulting in decreased levels of NADPH. 3. The enzyme was inactivated above 50 degrees or on storage at 4 degrees for longer than 24 h. The pH optimum was between 7-0-8-0. 4. the enzyme has been differentiated from NADPH-methaemoglobin reductase, NADPH-cytochrome c reductase, glutathione reductase, alpha,beta-unsaturated ketone reductase and aromatic alpha-keto acid reductase activities, but similarities exist between this enzyme and a rabbit kidney cortex aromatic aldehyde/ketone reductase."}
{"id": "PMID:239489", "title": "The metabolism of foreign compounds in the cestode, Moniezia expansa, and the nematode, Ascaris lumbricoides var suum.", "content": "1. The ability of the cestode Moniezia expansa and the nematode Ascaris lumbricoides var suum to metabolize foreign compounds has been assessed. 2. Both species were unable to oxidase aldrin, aniline, biphenyl, butylbenzene and nitrobenzene or to demethylate aminopyrine, and 4-nitroanisole. 3. M. expansa and A. lumbricoides var suum readily induced 4-nitroanisole, nitrobenzene, 4-nitrobenzoic acid and 4-nitrophenol to the corresponding amines. Azobenzene, dimethylaminoazobenzene, and 1,2-dimethyl-4-(4-carboxyphenylazo)-5-hydroxybenzene were also reduced. 4. Hydrolysis of esters, acetanilide, acetylsalicylic acid, aryl sulphates and aryl phosphates took place readily. However, beta-glucuronides were not hydrolysed. 5. The following reactions were not detected in either species: phosphate, sulphate, beta-glucuronide or beta-glycoside conjugation of phenolic compounds; acetylation of amino compounds, or the formation of glycine conjugates with 4-aminobenzoic acid or benzoic acid. 6. Male nematodes showed a higher rate of drug metabolism than female nematodes.", "contents": "The metabolism of foreign compounds in the cestode, Moniezia expansa, and the nematode, Ascaris lumbricoides var suum. 1. The ability of the cestode Moniezia expansa and the nematode Ascaris lumbricoides var suum to metabolize foreign compounds has been assessed. 2. Both species were unable to oxidase aldrin, aniline, biphenyl, butylbenzene and nitrobenzene or to demethylate aminopyrine, and 4-nitroanisole. 3. M. expansa and A. lumbricoides var suum readily induced 4-nitroanisole, nitrobenzene, 4-nitrobenzoic acid and 4-nitrophenol to the corresponding amines. Azobenzene, dimethylaminoazobenzene, and 1,2-dimethyl-4-(4-carboxyphenylazo)-5-hydroxybenzene were also reduced. 4. Hydrolysis of esters, acetanilide, acetylsalicylic acid, aryl sulphates and aryl phosphates took place readily. However, beta-glucuronides were not hydrolysed. 5. The following reactions were not detected in either species: phosphate, sulphate, beta-glucuronide or beta-glycoside conjugation of phenolic compounds; acetylation of amino compounds, or the formation of glycine conjugates with 4-aminobenzoic acid or benzoic acid. 6. Male nematodes showed a higher rate of drug metabolism than female nematodes."}
{"id": "PMID:239490", "title": "4-Nitrobenzoic acid reductase of the nematode Ascaris lumbricoides var suum. Localization of the enzyme and optimum assay conditions.", "content": "1. Reduction of 4-nitrobenzoic acid by the nematode Ascaris lumbricoides var suum occurred in the intestinal brush border cells. Cuticle, mesenchyme fluid and reproductive tissue showed no activity. 2. 4-Nitrobenzoic acid reductase was in the supernatant fraction after centrifugation of intestinal homogenates at 75 000 g for 2 h. 3. The enzyme required as cofactors NADH2, a low molecular weight thiol such as glutathione or cysteine and a divalent metal ion such as Mn++ or Cu++. The reduction  was not catalysed by NADPH2. 4. Reduction was not inhibited by O2 or CO. Optimum pH of the reaction was about 6.5.", "contents": "4-Nitrobenzoic acid reductase of the nematode Ascaris lumbricoides var suum. Localization of the enzyme and optimum assay conditions. 1. Reduction of 4-nitrobenzoic acid by the nematode Ascaris lumbricoides var suum occurred in the intestinal brush border cells. Cuticle, mesenchyme fluid and reproductive tissue showed no activity. 2. 4-Nitrobenzoic acid reductase was in the supernatant fraction after centrifugation of intestinal homogenates at 75 000 g for 2 h. 3. The enzyme required as cofactors NADH2, a low molecular weight thiol such as glutathione or cysteine and a divalent metal ion such as Mn++ or Cu++. The reduction  was not catalysed by NADPH2. 4. Reduction was not inhibited by O2 or CO. Optimum pH of the reaction was about 6.5."}
{"id": "PMID:239491", "title": "Glutathione conjugates as metabolites of benz[a]anthracene.", "content": "1. [3H]Benz[a]anthracene is converted into water-soluble metabolites by microsomal plus soluble fractions of rat-liver in the presence of NADPH and glutathione. Chromatography on Sephadex G25 gave four radioactive peaks; the first contained hydrocarbon or hydrocarbon derivatives bound to soluble protein while the other three peaks contained glutathione conjugates of hydrocarbon metabolites. 2. Conjugates formed when either of the benz[a]anthracene metabolites, 5,6-dihydro-5,6-dihydroxybenz[a]anthracene or 8,9-dihydro-8,9-dihydroxybenz[a]anthracene, were similarly incubated were probably S-(5,6,8,9-tetrahydro-5,6,9-trihydroxybenz[a]anthracen-8-yl)glutathione and S-(5,6,8,9-tetrahydro-6,8,9-trihydroxybena[a]anthracen-5-yl)glutathione respectively. The corresponding peak obtained in the metabolism of benz[a]anthracene probably contains a mixture of these two isomers. 3. The third peak contained the conjugate, S-(5,6-dihydro-l-hydroxybenz-[a]anthracen-k-yl)glutathione, also formed by the conjugation of the \"K-region\" epoxide of benz[a]anthracene with glutathione. This was not formed in the metabolism of the dihydrodiols. 4. The fourth peak contained a new type of conjugate that is probably S-(8,9,10,11-tetrahydro-8,9,10-trihydroxybenz[a]anthracen-11-yl)glutathione. This conjugate is chromatographically similar to a product obtained from incubation of the 8,9-dihydrodiol, and is probably formed by microsomal oxidation of the 10,11-bond of the dihydrodiol, followed by conjugation of the resulting diol-epoxide with glutathione.", "contents": "Glutathione conjugates as metabolites of benz[a]anthracene. 1. [3H]Benz[a]anthracene is converted into water-soluble metabolites by microsomal plus soluble fractions of rat-liver in the presence of NADPH and glutathione. Chromatography on Sephadex G25 gave four radioactive peaks; the first contained hydrocarbon or hydrocarbon derivatives bound to soluble protein while the other three peaks contained glutathione conjugates of hydrocarbon metabolites. 2. Conjugates formed when either of the benz[a]anthracene metabolites, 5,6-dihydro-5,6-dihydroxybenz[a]anthracene or 8,9-dihydro-8,9-dihydroxybenz[a]anthracene, were similarly incubated were probably S-(5,6,8,9-tetrahydro-5,6,9-trihydroxybenz[a]anthracen-8-yl)glutathione and S-(5,6,8,9-tetrahydro-6,8,9-trihydroxybena[a]anthracen-5-yl)glutathione respectively. The corresponding peak obtained in the metabolism of benz[a]anthracene probably contains a mixture of these two isomers. 3. The third peak contained the conjugate, S-(5,6-dihydro-l-hydroxybenz-[a]anthracen-k-yl)glutathione, also formed by the conjugation of the \"K-region\" epoxide of benz[a]anthracene with glutathione. This was not formed in the metabolism of the dihydrodiols. 4. The fourth peak contained a new type of conjugate that is probably S-(8,9,10,11-tetrahydro-8,9,10-trihydroxybenz[a]anthracen-11-yl)glutathione. This conjugate is chromatographically similar to a product obtained from incubation of the 8,9-dihydrodiol, and is probably formed by microsomal oxidation of the 10,11-bond of the dihydrodiol, followed by conjugation of the resulting diol-epoxide with glutathione."}
{"id": "PMID:239492", "title": "Biochemically aberrant Salmonella enteritidis ser. newington from human sources in Connecticut.", "content": "Three isolates of a lactose-fermenting, xylose-negative variety of Salmonella enteritidis ser. newington, identical in biochemical and serological reactions and in the antibiogram, were recovered from three patients in different areas of Connecticut in January 1974. Hydrogen sulfide production was not visible in Salmonella-Shigella agar, in triple sugar iron agar, and in Kligler iron agar but was noticed in lysine iron agar and on XLD agar, among others. The amount of fermentable carbohydrates present was found to correlate with failure to show hydrogen sulfide production (pH effect). In contrast to lactose-fermenting Salmonella strains reported by other authors, we could not elicit a direct transfer of the lac(+) character at frequencies above 10(-6). An epidemiological follow-up remained unsuccessful. Recommendations for the recognition of similar strains are presented.", "contents": "Biochemically aberrant Salmonella enteritidis ser. newington from human sources in Connecticut. Three isolates of a lactose-fermenting, xylose-negative variety of Salmonella enteritidis ser. newington, identical in biochemical and serological reactions and in the antibiogram, were recovered from three patients in different areas of Connecticut in January 1974. Hydrogen sulfide production was not visible in Salmonella-Shigella agar, in triple sugar iron agar, and in Kligler iron agar but was noticed in lysine iron agar and on XLD agar, among others. The amount of fermentable carbohydrates present was found to correlate with failure to show hydrogen sulfide production (pH effect). In contrast to lactose-fermenting Salmonella strains reported by other authors, we could not elicit a direct transfer of the lac(+) character at frequencies above 10(-6). An epidemiological follow-up remained unsuccessful. Recommendations for the recognition of similar strains are presented."}
{"id": "PMID:239493", "title": "[Danger of fetal acidosis in vaginal delivery from breech presentation (author's transl)].", "content": "On the basis of our own experience and the literature the risk of acidosis, which corresponds to the risk of asphyxia, during vaginal delivery of breech presentations is examined. Compared with delivery of vertex presentation it is 3-10 times greater. The risk of acidosis does not depend on the duration of pregnancy and only a little on the parity of the mother. Even with carefully selective indication for primary Caesarean section it cannot be reduced below the high level. Typically there is acute compression of the cord at the end of the first or later stages of labor. Even with intensive intra-partum care it cannot safely be predicted with sufficient certainty. As a criterion of the efficiency of modern obstetrics the impact of acidosis in umbilical blood and its increase in breech presentation is discussed. Only systematic Caesaren section before or early in labor will lower the risk to that of vertex  presentation. This is done and recommended by the authors. Links between acdosis in umbilical blood and permanent cerebral damage are probable but by no means certain and their importance in unknown. Selective  indication for Caesarean section which has to be made generously, represents an acceptable alternative.", "contents": "[Danger of fetal acidosis in vaginal delivery from breech presentation (author's transl)]. On the basis of our own experience and the literature the risk of acidosis, which corresponds to the risk of asphyxia, during vaginal delivery of breech presentations is examined. Compared with delivery of vertex presentation it is 3-10 times greater. The risk of acidosis does not depend on the duration of pregnancy and only a little on the parity of the mother. Even with carefully selective indication for primary Caesarean section it cannot be reduced below the high level. Typically there is acute compression of the cord at the end of the first or later stages of labor. Even with intensive intra-partum care it cannot safely be predicted with sufficient certainty. As a criterion of the efficiency of modern obstetrics the impact of acidosis in umbilical blood and its increase in breech presentation is discussed. Only systematic Caesaren section before or early in labor will lower the risk to that of vertex  presentation. This is done and recommended by the authors. Links between acdosis in umbilical blood and permanent cerebral damage are probable but by no means certain and their importance in unknown. Selective  indication for Caesarean section which has to be made generously, represents an acceptable alternative."}
{"id": "PMID:239494", "title": "[Hypoxia and acidosis--morbidity (author's transl)].", "content": "A critical study based on 3291 analyses of blood from the umbilical cord, and the consequences. In routine analyses acidosis (pH 7.10) was found in 2.03%. This percentage is considered too high. Protracted labor carries special risks. Conventional and intensive care supervision, when risks are foreseen, are often ineffective, since 48.8% of acidoses were recognized only post partum. More general intensive observation with internal cardiotocography and microinvestigations of blood appears to be the only way in which the frequency of acidosis could be decisively reduced.", "contents": "[Hypoxia and acidosis--morbidity (author's transl)]. A critical study based on 3291 analyses of blood from the umbilical cord, and the consequences. In routine analyses acidosis (pH 7.10) was found in 2.03%. This percentage is considered too high. Protracted labor carries special risks. Conventional and intensive care supervision, when risks are foreseen, are often ineffective, since 48.8% of acidoses were recognized only post partum. More general intensive observation with internal cardiotocography and microinvestigations of blood appears to be the only way in which the frequency of acidosis could be decisively reduced."}
{"id": "PMID:239495", "title": "[The action of prostaglandin E2-induced pains on the metabolic and clotting systems of mother and child during birth (author's transl)].", "content": "11 pregnancies at term were terminated by dilatation of the uterine cervix, low amniotomy, and by intravenous administration of PGE2. The average infusion time was 4 hours 20 minutes, and the average total dose of PGE2 amounted to 0.2 mg. Parameters of acid-base changes, carbohydrate and energic state changes, gas metabolism, and changes in coagulation and fibrinolysis in mother and in fetus were analysed during labor and after birth. Labor activity and fetal cardiac action were monitored cardiotocographically. Checked against 50 uncomplicated spontaneous deliveries, we have found no disadvantageous changes in the parameters investigated.", "contents": "[The action of prostaglandin E2-induced pains on the metabolic and clotting systems of mother and child during birth (author's transl)]. 11 pregnancies at term were terminated by dilatation of the uterine cervix, low amniotomy, and by intravenous administration of PGE2. The average infusion time was 4 hours 20 minutes, and the average total dose of PGE2 amounted to 0.2 mg. Parameters of acid-base changes, carbohydrate and energic state changes, gas metabolism, and changes in coagulation and fibrinolysis in mother and in fetus were analysed during labor and after birth. Labor activity and fetal cardiac action were monitored cardiotocographically. Checked against 50 uncomplicated spontaneous deliveries, we have found no disadvantageous changes in the parameters investigated."}
{"id": "PMID:239496", "title": "[Addition of gentamicine to polymethyl methacrylate for therapy of infectious bone diseases. Expeimental in vivo tests].", "content": "In experimental  in vivo tests the therapeutic effect of Gentamicin added to Palacos is detected in a standardized osteomyelitic infection caused by Staph. aureus haemolyticus. The number of germ populations is reduced significantly by the antibiotic which is released in a microbiologically active concentration. On the other hand the number of germ populations in control trials (without adding an antibiotic) is remaining on a high level. During the time of the tests the appearance of other bacterial is registrated.", "contents": "[Addition of gentamicine to polymethyl methacrylate for therapy of infectious bone diseases. Expeimental in vivo tests]. In experimental  in vivo tests the therapeutic effect of Gentamicin added to Palacos is detected in a standardized osteomyelitic infection caused by Staph. aureus haemolyticus. The number of germ populations is reduced significantly by the antibiotic which is released in a microbiologically active concentration. On the other hand the number of germ populations in control trials (without adding an antibiotic) is remaining on a high level. During the time of the tests the appearance of other bacterial is registrated."}
{"id": "PMID:239500", "title": "[Tissue compatiblity of stomatologic materials in cell cultures].", "content": "The paper contains results of investigations on the suitability of cell cultures for biological testing of soluble substances from dental cements and their components. The preparation of the specimens as well as the elution process are described. Furthermore the culture system of cell populations in vitro and representative biological parameters are reported.", "contents": "[Tissue compatiblity of stomatologic materials in cell cultures]. The paper contains results of investigations on the suitability of cell cultures for biological testing of soluble substances from dental cements and their components. The preparation of the specimens as well as the elution process are described. Furthermore the culture system of cell populations in vitro and representative biological parameters are reported."}
{"id": "PMID:239502", "title": "[Biolgical problems of a manmade small lake (author's transl)].", "content": "In connection with an intensive hygienic supervision of public bathing facilities and the attempts to draw up a law on bathing hygiene, the lack of contamination standards for small lakes available to the public for bathing was particularly conspicuous. In addition to the current chemical and bacteriological routine examinations, a small bathing lake with a surface area of 3000 square metres containing about 7000 m3 of water and which has been in existence for over 10 years was objected to extensive biological investigations during the months July to September. The results of the analysis show a relatively constant hydrogen ion concentration (pH 8.2), small variations in electrolytic conductivity and 8 German degrees of hardness. The mean phosphourus level was 60 mug/L. the orthophosphate levels ranged between 5.2 and 18.5 mug/L. Oxygen saturation during the entire summer months was more than 100%. Altogether, 49 different kinds of phytoplankton- and 12 kinds of zooplancton-organisms were identified. The total biological mass of phytoplancton organisms was between 8.5 and 16 mg fresh weight per litre, bacterial biomass varied between 4.5 and 9.5 mg/l. Particularly striking for summer conditions was the high proportion of Cyclotella- and Synedra species among the phytoplancton mass, while the algal-bloom producing Microcystis flos aquae attained a maximum proportion of 15%. In spite of the great variety of its forms, green algae were present in small numbers only. The comparison of the described findings with the trophic-systems of HUTCHINSON, NYGAARD and RAWSON indicated an eutrophic type of lake; classification according to the types of the various saprobic systems of NAUMANN, KOLKWITZ and LIEBMANN yielded a predominantly beta-mesosaprobic type of lake. The investigations described show, however, that this is probably a lake rich in nutrients, but that there is a relatively stable biological equilibrium and that, consequently, there is no further threat of progressive eutrophism. Special hygienic parameters, contamination due to visitors and phytoplancton production will be reported in a second communication.", "contents": "[Biolgical problems of a manmade small lake (author's transl)]. In connection with an intensive hygienic supervision of public bathing facilities and the attempts to draw up a law on bathing hygiene, the lack of contamination standards for small lakes available to the public for bathing was particularly conspicuous. In addition to the current chemical and bacteriological routine examinations, a small bathing lake with a surface area of 3000 square metres containing about 7000 m3 of water and which has been in existence for over 10 years was objected to extensive biological investigations during the months July to September. The results of the analysis show a relatively constant hydrogen ion concentration (pH 8.2), small variations in electrolytic conductivity and 8 German degrees of hardness. The mean phosphourus level was 60 mug/L. the orthophosphate levels ranged between 5.2 and 18.5 mug/L. Oxygen saturation during the entire summer months was more than 100%. Altogether, 49 different kinds of phytoplankton- and 12 kinds of zooplancton-organisms were identified. The total biological mass of phytoplancton organisms was between 8.5 and 16 mg fresh weight per litre, bacterial biomass varied between 4.5 and 9.5 mg/l. Particularly striking for summer conditions was the high proportion of Cyclotella- and Synedra species among the phytoplancton mass, while the algal-bloom producing Microcystis flos aquae attained a maximum proportion of 15%. In spite of the great variety of its forms, green algae were present in small numbers only. The comparison of the described findings with the trophic-systems of HUTCHINSON, NYGAARD and RAWSON indicated an eutrophic type of lake; classification according to the types of the various saprobic systems of NAUMANN, KOLKWITZ and LIEBMANN yielded a predominantly beta-mesosaprobic type of lake. The investigations described show, however, that this is probably a lake rich in nutrients, but that there is a relatively stable biological equilibrium and that, consequently, there is no further threat of progressive eutrophism. Special hygienic parameters, contamination due to visitors and phytoplancton production will be reported in a second communication."}
{"id": "PMID:239503", "title": "[Randomised investigations of some Tyrolean swimming pools for the presence of Trichomonas vaginalis and pathogenic fungi (author's transl)].", "content": "Trichomonads were not demonstrated either microscopically or by culture in water samples from 15 public open air swimming pools in the Tyrol. On the other hand, a small number of pathogenic fungi (Candida albicans, Trichophyton mentagrophytes, Tr. verrucosum) were cultured from pool water with a free chlorine content of less than 0.35 mg/l (DPD 1). Dermatophytes could also be demonstrated by cultures of the coatings on the surfaces of tiles in the showers, and of pool surrounding-and cabin tract floors. (Candida albicans, Trichophyton mentagrophytes, Epidermophyton floccosum, Scopulariopsis brevicaulis).", "contents": "[Randomised investigations of some Tyrolean swimming pools for the presence of Trichomonas vaginalis and pathogenic fungi (author's transl)]. Trichomonads were not demonstrated either microscopically or by culture in water samples from 15 public open air swimming pools in the Tyrol. On the other hand, a small number of pathogenic fungi (Candida albicans, Trichophyton mentagrophytes, Tr. verrucosum) were cultured from pool water with a free chlorine content of less than 0.35 mg/l (DPD 1). Dermatophytes could also be demonstrated by cultures of the coatings on the surfaces of tiles in the showers, and of pool surrounding-and cabin tract floors. (Candida albicans, Trichophyton mentagrophytes, Epidermophyton floccosum, Scopulariopsis brevicaulis)."}
{"id": "PMID:239505", "title": "[Isolation of the causative agent of tularemia from Siberian lemmings in Eastern Taymyr].", "content": "The authors present the results of bacteriological and serological study for tularemia of 498 lemmings caught in Taimyr. Positive results were revealed in 4 out of 98 sera examined in the indirect hemagglutination test. In carrying out 67 biological tests on albino mice there were isolated for the first time in the Soviet Union 6 cultures of the causative agent of tularemia from the spleen of lemmings. By morphological, cultural and virulent properties the cultures obtained failed to differ from those isolated in other regions of the Soviet Union, and, consequently, we referred to the holoarctic race. Thus, it was established by the authors (both serologically and bacteriologically) that there existed tundra foci of tularemia.", "contents": "[Isolation of the causative agent of tularemia from Siberian lemmings in Eastern Taymyr]. The authors present the results of bacteriological and serological study for tularemia of 498 lemmings caught in Taimyr. Positive results were revealed in 4 out of 98 sera examined in the indirect hemagglutination test. In carrying out 67 biological tests on albino mice there were isolated for the first time in the Soviet Union 6 cultures of the causative agent of tularemia from the spleen of lemmings. By morphological, cultural and virulent properties the cultures obtained failed to differ from those isolated in other regions of the Soviet Union, and, consequently, we referred to the holoarctic race. Thus, it was established by the authors (both serologically and bacteriologically) that there existed tundra foci of tularemia."}
{"id": "PMID:239506", "title": "[Development of new types of chemical vaccine for prevention of intestinal infections and problems of their qualitative evaluation. III. Comparative study of immunologic characteristics of experimental antigenic preparations].", "content": "As a result of comparative study of the immunological properties and antigenic activity of thyphoid, paratyphoid A and B and Sonne and Flexner dysentery antigenic preparations obtained by various methods there was revealed a decreased toxicity of the experimental preparations of the Tashkent and Leningrad Institute of Vaccines and Sera (in comparison with the tryptic antigens) and a considerable advantages of the experimental thyphoid and paratyphoid antigenic preparations by their capacity to induce the H-antibody formation in the presence of the O-antigenic activity. The preparations of the Moscow Institute of Vaccines and Sera had increased toxicity. The detected advantages of the experimental antigenic preparations of the Tashkent and Leningrad Institute of Vaccines and Sera permitted to recommend the method used in their making to obtain new chemical vaccines against the intestinal infections.", "contents": "[Development of new types of chemical vaccine for prevention of intestinal infections and problems of their qualitative evaluation. III. Comparative study of immunologic characteristics of experimental antigenic preparations]. As a result of comparative study of the immunological properties and antigenic activity of thyphoid, paratyphoid A and B and Sonne and Flexner dysentery antigenic preparations obtained by various methods there was revealed a decreased toxicity of the experimental preparations of the Tashkent and Leningrad Institute of Vaccines and Sera (in comparison with the tryptic antigens) and a considerable advantages of the experimental thyphoid and paratyphoid antigenic preparations by their capacity to induce the H-antibody formation in the presence of the O-antigenic activity. The preparations of the Moscow Institute of Vaccines and Sera had increased toxicity. The detected advantages of the experimental antigenic preparations of the Tashkent and Leningrad Institute of Vaccines and Sera permitted to recommend the method used in their making to obtain new chemical vaccines against the intestinal infections."}
{"id": "PMID:239507", "title": "[Pathomorphological and immunofluorescent studies of smallpox vaccine neurotropism].", "content": "Experiments were conducted on guinea pigs sensitized with the AK C-vaccine components. In intracardiac injection with smallpox vaccine there was shown a possibility of development of marked hemodynamic disturbances, of the inflammatory-dystrophic processes of irreversibel character, with a subsequent neuronophagia and demyelinization. Injection of smallpox vaccine into the circulation of intact guinea pigs was accompanied by development in the nervous system of insignificant circulatory disturbances and of the inflammatory dystrophic phenomena of reversible character. A method of immunofluorescence was used and the antigen of the vaccine virus was revealed in the neurons of the brain and the spinal cord of the sensitized and intact animals. Marked hemodynamic and insignificant inflammatory-dystrophic processes were revealed in the nervous system of a child which died of the post-vaccinal encephalitis; an antigen of the smallpox virus was found by the immunofluorescent method in the nerve cells and the vessels in various portions of the nervous system.", "contents": "[Pathomorphological and immunofluorescent studies of smallpox vaccine neurotropism]. Experiments were conducted on guinea pigs sensitized with the AK C-vaccine components. In intracardiac injection with smallpox vaccine there was shown a possibility of development of marked hemodynamic disturbances, of the inflammatory-dystrophic processes of irreversibel character, with a subsequent neuronophagia and demyelinization. Injection of smallpox vaccine into the circulation of intact guinea pigs was accompanied by development in the nervous system of insignificant circulatory disturbances and of the inflammatory dystrophic phenomena of reversible character. A method of immunofluorescence was used and the antigen of the vaccine virus was revealed in the neurons of the brain and the spinal cord of the sensitized and intact animals. Marked hemodynamic and insignificant inflammatory-dystrophic processes were revealed in the nervous system of a child which died of the post-vaccinal encephalitis; an antigen of the smallpox virus was found by the immunofluorescent method in the nerve cells and the vessels in various portions of the nervous system."}
{"id": "PMID:239508", "title": "Complexes of derivatives of 1-nitro-9-aminoacridine with DNA.", "content": "Substituted 1-nitro-9-aminoacridine derivatives were shown to inhibit RNA and to a lesser extent protein synthesis in cultured human cells. Complex formation between the compounds studied and DNA were considered to be responsible for their cytostatic action. Two types of complexes differing in their binding forces were found. The biological activity of the studied compounds seems not to be dependent on the existence of a positive charge on the acridine ring.", "contents": "Complexes of derivatives of 1-nitro-9-aminoacridine with DNA. Substituted 1-nitro-9-aminoacridine derivatives were shown to inhibit RNA and to a lesser extent protein synthesis in cultured human cells. Complex formation between the compounds studied and DNA were considered to be responsible for their cytostatic action. Two types of complexes differing in their binding forces were found. The biological activity of the studied compounds seems not to be dependent on the existence of a positive charge on the acridine ring."}
{"id": "PMID:239509", "title": "Synthesis and properties on some 2-, 4- and 5-aminopyrimidines. Effect of -NH2 and ortho-C methylation on protolytic equilibria and electronic absorption spectra.", "content": "A number of new 2-, 4- and 5-aminopyrimidines with sterical hindrance to the amino group rotation were synthesized. The pKa values and u.v. absorption spectra of the aminopyrimidines were measured in order to elucidate the conformation of the amino group depending on the place of substitution.", "contents": "Synthesis and properties on some 2-, 4- and 5-aminopyrimidines. Effect of -NH2 and ortho-C methylation on protolytic equilibria and electronic absorption spectra. A number of new 2-, 4- and 5-aminopyrimidines with sterical hindrance to the amino group rotation were synthesized. The pKa values and u.v. absorption spectra of the aminopyrimidines were measured in order to elucidate the conformation of the amino group depending on the place of substitution."}
{"id": "PMID:239510", "title": "Tyrosine aminotransferase in frog liver.", "content": "1. In frog liver, tyrosine aminotransferase is located mainly in cytoplasm. The enzyme is an anionic protein of mol. wt. 115 000 daltons, specific toward 2-oxoglutarate. The enzyme separates on ion-exchange chromatography into two active forms. 2. Administration of triiodotyronine in vivo induces the activity of the enzyme. Epinephrine and glucagon have no effect, and cAMP and insulin repress this activity by about 70%. 3. Triiodotyronine stimulates incorporation of [14C]leucine into protein, and the amount of the enzyme in the nacent polysome-bound protein is considerably increased.", "contents": "Tyrosine aminotransferase in frog liver. 1. In frog liver, tyrosine aminotransferase is located mainly in cytoplasm. The enzyme is an anionic protein of mol. wt. 115 000 daltons, specific toward 2-oxoglutarate. The enzyme separates on ion-exchange chromatography into two active forms. 2. Administration of triiodotyronine in vivo induces the activity of the enzyme. Epinephrine and glucagon have no effect, and cAMP and insulin repress this activity by about 70%. 3. Triiodotyronine stimulates incorporation of [14C]leucine into protein, and the amount of the enzyme in the nacent polysome-bound protein is considerably increased."}
{"id": "PMID:239511", "title": "Radiation-induced aldehydes in collagen.", "content": "Aldehydes present in native and irradiated (30 krad) collagen were separated from its enzymic degradation products using molecular-sieve chromatography on Bio-Gel P-2 column. From the absorption spectra of N-methylbenzothiazolone hydrazone derivatives it was concluded that two out of five of the aldehydes separated from the irradiated collagen, were identical with those present in control collagen. The possible origin of three other aldehydes is discussed.", "contents": "Radiation-induced aldehydes in collagen. Aldehydes present in native and irradiated (30 krad) collagen were separated from its enzymic degradation products using molecular-sieve chromatography on Bio-Gel P-2 column. From the absorption spectra of N-methylbenzothiazolone hydrazone derivatives it was concluded that two out of five of the aldehydes separated from the irradiated collagen, were identical with those present in control collagen. The possible origin of three other aldehydes is discussed."}
{"id": "PMID:239512", "title": "Isolation and properties of poly(A)-containing RNA from the cytoplasm of rat liver cells.", "content": "1. The described technique for preparative isolation of poly(A)-containing RNA by complexing with poly(U)-cellulose and elution at 45 degrees C, is simple, reproducible, and the poly(U)-cellulose preparation is suitable for repeated use. 2. The poly(A)-containing RNA isolated from the poly(U)-cellulose complex is still contaminated by ribosomal RNA which can be removed by recomplexing. The purified preparation is heterogeneous on polyacrylamide-gel electrophoresis and is located over the region from 5-6S to 28S. Poly(A) segments of cytoplasmic RNA show heterogeneous size distribution. 3. In acidic medium, the poly(A) segments form ordered double-stranded structure. 4. The rapid labelling of rat liver and fibroblast cytoplasmic poly(A)-containing RNAs and their base composition resemble closely the corresponding properties of mRNA.", "contents": "Isolation and properties of poly(A)-containing RNA from the cytoplasm of rat liver cells. 1. The described technique for preparative isolation of poly(A)-containing RNA by complexing with poly(U)-cellulose and elution at 45 degrees C, is simple, reproducible, and the poly(U)-cellulose preparation is suitable for repeated use. 2. The poly(A)-containing RNA isolated from the poly(U)-cellulose complex is still contaminated by ribosomal RNA which can be removed by recomplexing. The purified preparation is heterogeneous on polyacrylamide-gel electrophoresis and is located over the region from 5-6S to 28S. Poly(A) segments of cytoplasmic RNA show heterogeneous size distribution. 3. In acidic medium, the poly(A) segments form ordered double-stranded structure. 4. The rapid labelling of rat liver and fibroblast cytoplasmic poly(A)-containing RNAs and their base composition resemble closely the corresponding properties of mRNA."}
{"id": "PMID:239513", "title": "Changes of the oxidative phosphorylation in mitchondria of rat skeletal muscle following strenous exercise.", "content": "The rate of oxygen consumption of mitochondria from rat muscles at pH 7.4 is elevated by 1-lactate. The respiratory control ratio and the ADP/O-ratio are decreased under these conditions. Acidification to pH 6.5 in the absence of 1-lactate does not change the interpreted mitochondrial functions. The experimental data are discussed as a partial uncoupling effect of 1-lactate on the oxidative phosphorylation. Similar changes in those mitochondrial functions are found after short-time intensive swimming exercise of rats. These variations might be a reason for the sometimes described reduced aerobic performance after intensive work.", "contents": "Changes of the oxidative phosphorylation in mitchondria of rat skeletal muscle following strenous exercise. The rate of oxygen consumption of mitochondria from rat muscles at pH 7.4 is elevated by 1-lactate. The respiratory control ratio and the ADP/O-ratio are decreased under these conditions. Acidification to pH 6.5 in the absence of 1-lactate does not change the interpreted mitochondrial functions. The experimental data are discussed as a partial uncoupling effect of 1-lactate on the oxidative phosphorylation. Similar changes in those mitochondrial functions are found after short-time intensive swimming exercise of rats. These variations might be a reason for the sometimes described reduced aerobic performance after intensive work."}
{"id": "PMID:239514", "title": "Redox metabolism of glutathione in the red blood cell.", "content": "A theoretical study of the biochemical and clinical aspects of the reduction-oxidation metabolism of glutathione in the mature red blood cell is presented. A summarizing survey of the literature data has led to the formulation of a mathematical model which comprises the kinetic properties of the enzymes partaking in the hexose monophosphate pathway (HMP) and the oxidation of NADPH and GSH. The model takes the form of a system of differential equations describing the motion of metabolites in one cell. The interactions between metabolites ane enzymes, in particular between glutathione and the SH-dependent enzymes of glucose phosphorylation and HMP have been included into the model...", "contents": "Redox metabolism of glutathione in the red blood cell. A theoretical study of the biochemical and clinical aspects of the reduction-oxidation metabolism of glutathione in the mature red blood cell is presented. A summarizing survey of the literature data has led to the formulation of a mathematical model which comprises the kinetic properties of the enzymes partaking in the hexose monophosphate pathway (HMP) and the oxidation of NADPH and GSH. The model takes the form of a system of differential equations describing the motion of metabolites in one cell. The interactions between metabolites ane enzymes, in particular between glutathione and the SH-dependent enzymes of glucose phosphorylation and HMP have been included into the model..."}
{"id": "PMID:239515", "title": "[Phosphatidylcholine transfer between liposomes and mitochondria. Testing system for the study of specific phospholipid exchange].", "content": "A system consisting of liposomes and mitochondria for studying the exchange of specific phospholipids is described. The liposomes were prepared from phosphatidylcholine labelled with 14C-palmitic acid. The transfer of liposomes to the mitochondria is specifically stimulated 2- to 3fold by the pH 5.1 supernatant, and proceeds in a linear fashion for 90 min.", "contents": "[Phosphatidylcholine transfer between liposomes and mitochondria. Testing system for the study of specific phospholipid exchange]. A system consisting of liposomes and mitochondria for studying the exchange of specific phospholipids is described. The liposomes were prepared from phosphatidylcholine labelled with 14C-palmitic acid. The transfer of liposomes to the mitochondria is specifically stimulated 2- to 3fold by the pH 5.1 supernatant, and proceeds in a linear fashion for 90 min."}
{"id": "PMID:239516", "title": "Specific receptors for prolactin in the ovary.", "content": "A role of prolactin (PRL) in ovarian function has been suggested in several species, but not unequivocally established except in the rat. We, therefore, examined the presence of specific receptor for PRL in ovaries of rat, cow, and human. Human PRL (hPRL) labelled with 125I by the lactoperoxidase method was shown to be capable of specific binding to rat mammary tissue homogenate. Human, cow, and rat ovarian homogenates and/or partially purified plasma membranes were also shown to specifically bind 125I-hPRL. Binding was a saturable phenomenon and was dependent on receptor protein concentration. Optimal binding was observed at pH 7.0 and 37 degrees C. Binding was reversibly inhibited by exposure of membranes to pH 10.0 and irreversibly destroyed by exposure to pH 3.0. Bound 125I-hPRL was displaceable by unlabelled human, ovine, and bovine PRL but not by FSH or LH. However, human chorionic somatomammotrophin (hCS) and hGH showed some competition with 125I-hPRL. Number of binding sites/mg protein was lowest (0.8 x 10(-12)M) during metoestrus and increased during dioestrus (11 x 10(-12)M) reaching the maximum number at  pro-oestrus (24.6 x 10(-12)M). These results demonstrate that presence of specific PRL receptor in the ovaries and are consistent with a role of PRL at the ovarian level.", "contents": "Specific receptors for prolactin in the ovary. A role of prolactin (PRL) in ovarian function has been suggested in several species, but not unequivocally established except in the rat. We, therefore, examined the presence of specific receptor for PRL in ovaries of rat, cow, and human. Human PRL (hPRL) labelled with 125I by the lactoperoxidase method was shown to be capable of specific binding to rat mammary tissue homogenate. Human, cow, and rat ovarian homogenates and/or partially purified plasma membranes were also shown to specifically bind 125I-hPRL. Binding was a saturable phenomenon and was dependent on receptor protein concentration. Optimal binding was observed at pH 7.0 and 37 degrees C. Binding was reversibly inhibited by exposure of membranes to pH 10.0 and irreversibly destroyed by exposure to pH 3.0. Bound 125I-hPRL was displaceable by unlabelled human, ovine, and bovine PRL but not by FSH or LH. However, human chorionic somatomammotrophin (hCS) and hGH showed some competition with 125I-hPRL. Number of binding sites/mg protein was lowest (0.8 x 10(-12)M) during metoestrus and increased during dioestrus (11 x 10(-12)M) reaching the maximum number at  pro-oestrus (24.6 x 10(-12)M). These results demonstrate that presence of specific PRL receptor in the ovaries and are consistent with a role of PRL at the ovarian level."}
{"id": "PMID:239517", "title": "A new antihistamine hc20-511 compared with dimetinden (fenistil retard) in the treatment of chronic urticaria and other pruritic dermatoses.", "content": "The new antihistamine, HC20-511 (Sandoz), was compared with Dimetinden (Fenistil retard) in a single-blind comparative study in 42 patients with dermatoses, 28 of whom suffered from chronic urticaria. HC20-511 had a better effect, especially in chronic urticaria, where pruritus, erythema and papules quickly disappeared. The effect appeared somewhat faster than and lasted as long as that of Dimetinden, although HC20-511 is not a retard-preparation unlike the Dimetinden preparation used for comparison. HC20-511 also caused less side effects.", "contents": "A new antihistamine hc20-511 compared with dimetinden (fenistil retard) in the treatment of chronic urticaria and other pruritic dermatoses. The new antihistamine, HC20-511 (Sandoz), was compared with Dimetinden (Fenistil retard) in a single-blind comparative study in 42 patients with dermatoses, 28 of whom suffered from chronic urticaria. HC20-511 had a better effect, especially in chronic urticaria, where pruritus, erythema and papules quickly disappeared. The effect appeared somewhat faster than and lasted as long as that of Dimetinden, although HC20-511 is not a retard-preparation unlike the Dimetinden preparation used for comparison. HC20-511 also caused less side effects."}
{"id": "PMID:239518", "title": "Effect of pH, temperature and incubation period on the study of intrinsic innervation of various organs by thiocholine technique in certain vertebrates.", "content": "The adrenergic fibres can be demonstrated if the optimal time and temperature are maintained. The cholinergic fibres were demonstrated at pH 5.2, incubation period l4h and temperature 37 degrees C. To ascertain the cholinesterase activity in tongue, heart, lung(birds, mammals and reptiles), gizzard and proventriculus (birds) and penis (rat and embryo of squirrel), pH 4.9, 16h incubation and temperature 37 degrees C, were quite suitable. It was possible to demonstrate the intrinsic innervation in tongue, lung, heart (mammals, birds and reptiles), gizzard and proventriculus (birds) and penis (rat and embryo of squirrel), at pH 5.2, 20h incubation and temperature 40 degrees C.", "contents": "Effect of pH, temperature and incubation period on the study of intrinsic innervation of various organs by thiocholine technique in certain vertebrates. The adrenergic fibres can be demonstrated if the optimal time and temperature are maintained. The cholinergic fibres were demonstrated at pH 5.2, incubation period l4h and temperature 37 degrees C. To ascertain the cholinesterase activity in tongue, heart, lung(birds, mammals and reptiles), gizzard and proventriculus (birds) and penis (rat and embryo of squirrel), pH 4.9, 16h incubation and temperature 37 degrees C, were quite suitable. It was possible to demonstrate the intrinsic innervation in tongue, lung, heart (mammals, birds and reptiles), gizzard and proventriculus (birds) and penis (rat and embryo of squirrel), at pH 5.2, 20h incubation and temperature 40 degrees C."}
{"id": "PMID:239519", "title": "Ventricular fluid lactate, pyruvate, bicarbonate and ph in unconscious brain-injured patients subjected to controlled ventilation.", "content": "In 35 unconscious patients suffering from traumatic brain injury and subjected to controlled hyperventilation within 12 hours of the acute trauma, we measured continuously the intraventricular pressure (IVP), ventricular fluid lactate, pyruvate, L/P ratio, pH and bicarbonate during the first 4 posttraumatic days, and related the findings to the clinical course. In patients in whom the follow-up study did not reveal severe mental impairment or dementia, the ventricular fluid lactate never exceeded 4 mmol/litre. In this group, the IVP level never exceeded 40 mmHg/hour, and the mean pressure/day never exceeded 20 mmHg. In half of the patients in whom dementia, vegetative survival or death occurred, ventricular fluid lactate exceeded 4 mmol/litre; the IVP level/hour exceeded 40 mmHg in two of 23 patients, and the mean pressure/day exceeded 20 mmHg in nine of 23 patients. The prognostic value of pyruvate was of less importance, although a significant increase in patients with a poor outcome was seen. No prognostic conclusions could be drawn from ventricular fluid, L/P ratio, pH and bicarbonate.", "contents": "Ventricular fluid lactate, pyruvate, bicarbonate and ph in unconscious brain-injured patients subjected to controlled ventilation. In 35 unconscious patients suffering from traumatic brain injury and subjected to controlled hyperventilation within 12 hours of the acute trauma, we measured continuously the intraventricular pressure (IVP), ventricular fluid lactate, pyruvate, L/P ratio, pH and bicarbonate during the first 4 posttraumatic days, and related the findings to the clinical course. In patients in whom the follow-up study did not reveal severe mental impairment or dementia, the ventricular fluid lactate never exceeded 4 mmol/litre. In this group, the IVP level never exceeded 40 mmHg/hour, and the mean pressure/day never exceeded 20 mmHg. In half of the patients in whom dementia, vegetative survival or death occurred, ventricular fluid lactate exceeded 4 mmol/litre; the IVP level/hour exceeded 40 mmHg in two of 23 patients, and the mean pressure/day exceeded 20 mmHg in nine of 23 patients. The prognostic value of pyruvate was of less importance, although a significant increase in patients with a poor outcome was seen. No prognostic conclusions could be drawn from ventricular fluid, L/P ratio, pH and bicarbonate."}
{"id": "PMID:239520", "title": "The influence of changes in the environment on twitching motility.", "content": "By examining medium composition and cultural conditions quantitatively it was possible to define conditions suitable to bring twitching motility about. Such conditions include the use of freshly poured, relatively thick and only slightly dried plates of a dilute medium in which the agar concentration is not too high. Incubation should take place in a humid atmosphere. In fact, everything points to the humidity as a factor of the utmost importance. Using strains of Acinetobacter calcoaceticus, it was found that a pH value of the medium adjusted to 9.0 enhances twitching motility. Spreading growth was not produced if agarose was applied instead of ordinary agars. Twitching motility was inhibited by a number of different chlorides, potassium nitrate, Tween 80 and sodium taurocholate. Possible interpretations of these observations are discussed.", "contents": "The influence of changes in the environment on twitching motility. By examining medium composition and cultural conditions quantitatively it was possible to define conditions suitable to bring twitching motility about. Such conditions include the use of freshly poured, relatively thick and only slightly dried plates of a dilute medium in which the agar concentration is not too high. Incubation should take place in a humid atmosphere. In fact, everything points to the humidity as a factor of the utmost importance. Using strains of Acinetobacter calcoaceticus, it was found that a pH value of the medium adjusted to 9.0 enhances twitching motility. Spreading growth was not produced if agarose was applied instead of ordinary agars. Twitching motility was inhibited by a number of different chlorides, potassium nitrate, Tween 80 and sodium taurocholate. Possible interpretations of these observations are discussed."}
{"id": "PMID:239521", "title": "Boric acid tolerant Vibrio cholerae: biological and physical properties.", "content": "Two boric acid tolerant variants were developed by passage in boric acid containing media from a mouse virulent parent Vibrio cholerae strain. The variants were stable, exhibited increased acid resistance, were less virulent to mice, but protected against challenge with the mouse virulent parent strain.", "contents": "Boric acid tolerant Vibrio cholerae: biological and physical properties. Two boric acid tolerant variants were developed by passage in boric acid containing media from a mouse virulent parent Vibrio cholerae strain. The variants were stable, exhibited increased acid resistance, were less virulent to mice, but protected against challenge with the mouse virulent parent strain."}
{"id": "PMID:239522", "title": "Airway effects of slow reacting substance, prostaglandin F2alpha and histamine in the guinea-pig.", "content": "SRS, PGF2chi, and histamine were administered intravenously or as aerosols to artifically ventilated guinea-pigs in order to asses their capacity to affect tracheal insufflation pressure measured by means of Konzett-R\u00f6ssler technique, Independently of route of administration all three compounds increased tracheal insufflation pressure, SRS being the most potent one. Bilateral cervical vagotomy did not alter the effect. Relative to histamine SRS and PGF2chi were considerably more active by aerosol administration than by intranvenous injection. The aerosols had little or no effect on systemic blood pressure. On intravenous injection, histamine decreased and SRS and PGF2chi increased arterial blood pressure in a dose-dependent fashion. The airway effects of histamine were correlated to those on blood pressure whereas with SRS and PGF2chi this was not seen when the blood pressure effects were marked. Preadministration of adrenaline or isoprenaline as aerosols antagonized the increase in insufflation pressure, but not the effects on blood pressure, produced by intravenously injected histamine or PGF2chi. It is concluded that SRS, PGF2chi and histamine on intravenous or aerosol adminstration increase tracheal insufflation pressure in the guinea-pig mainly by an action on airway tone. The data emphasize that SRS is a potent bronchoconstricting agent, possibly of pathophysiological significance in guinea-pig anaphylaxis.", "contents": "Airway effects of slow reacting substance, prostaglandin F2alpha and histamine in the guinea-pig. SRS, PGF2chi, and histamine were administered intravenously or as aerosols to artifically ventilated guinea-pigs in order to asses their capacity to affect tracheal insufflation pressure measured by means of Konzett-R\u00f6ssler technique, Independently of route of administration all three compounds increased tracheal insufflation pressure, SRS being the most potent one. Bilateral cervical vagotomy did not alter the effect. Relative to histamine SRS and PGF2chi were considerably more active by aerosol administration than by intranvenous injection. The aerosols had little or no effect on systemic blood pressure. On intravenous injection, histamine decreased and SRS and PGF2chi increased arterial blood pressure in a dose-dependent fashion. The airway effects of histamine were correlated to those on blood pressure whereas with SRS and PGF2chi this was not seen when the blood pressure effects were marked. Preadministration of adrenaline or isoprenaline as aerosols antagonized the increase in insufflation pressure, but not the effects on blood pressure, produced by intravenously injected histamine or PGF2chi. It is concluded that SRS, PGF2chi and histamine on intravenous or aerosol adminstration increase tracheal insufflation pressure in the guinea-pig mainly by an action on airway tone. The data emphasize that SRS is a potent bronchoconstricting agent, possibly of pathophysiological significance in guinea-pig anaphylaxis."}
{"id": "PMID:239523", "title": "Transcapillary fluid movements in sympathectomized intestine and skin during hemorrhagic hypotension.", "content": "Net transcapilary fluid exchange in skin tissue (paw) and small intestine was observed during a 90 min period of hemorrhagic hypotension at 50 mm Hg in the cat. Reflex fluid transfer was prevented by regional sympathectomy and chi-adrenergic blockade. Early in hemorrhage, fluid absorption from the extravascular space occurred in both tissues, apparently caused by osmosis. The process was thus co-ordinated in time with a positive arterio-venous osmolar difference, in turn caused by a marked arterial hypersomolality. Experimetnal arterial hyperosomolality of similar magnitude, created by i.v. infusion of hypertonic glucose in non-bled animals, led to transcapillary fluid absorption in both intestine and skin and at rates similar to those in bleeding. Regional hypotsionen per se caused no fluid absorption. Later in hemorrhage (greater than 30 min), plasma fluid moved into the extravascular space both in skin and intestine, apparently due to a gradual increase of cappilary hydrostatic pressure. It is concluded that the arterial hypersomolality during bleeding can cause transcapillary fluid absorption in intestinal and skin tissues, as previously shown for skeletal muscle (J\u00e4rhult 1973). The hemodynamic significance of this process for plasma volume regulation in hemorrhage is, however, much greater in skeletal muscle than in intestine and skin, mainly due to the much larger total mass of the muscle tissue.", "contents": "Transcapillary fluid movements in sympathectomized intestine and skin during hemorrhagic hypotension. Net transcapilary fluid exchange in skin tissue (paw) and small intestine was observed during a 90 min period of hemorrhagic hypotension at 50 mm Hg in the cat. Reflex fluid transfer was prevented by regional sympathectomy and chi-adrenergic blockade. Early in hemorrhage, fluid absorption from the extravascular space occurred in both tissues, apparently caused by osmosis. The process was thus co-ordinated in time with a positive arterio-venous osmolar difference, in turn caused by a marked arterial hypersomolality. Experimetnal arterial hyperosomolality of similar magnitude, created by i.v. infusion of hypertonic glucose in non-bled animals, led to transcapillary fluid absorption in both intestine and skin and at rates similar to those in bleeding. Regional hypotsionen per se caused no fluid absorption. Later in hemorrhage (greater than 30 min), plasma fluid moved into the extravascular space both in skin and intestine, apparently due to a gradual increase of cappilary hydrostatic pressure. It is concluded that the arterial hypersomolality during bleeding can cause transcapillary fluid absorption in intestinal and skin tissues, as previously shown for skeletal muscle (J\u00e4rhult 1973). The hemodynamic significance of this process for plasma volume regulation in hemorrhage is, however, much greater in skeletal muscle than in intestine and skin, mainly due to the much larger total mass of the muscle tissue."}
{"id": "PMID:239524", "title": "Membrane potential and conductance during pinocytosis induced in Amoeba proteus with alkali metal ions.", "content": "An investigation of the relationship between the polarized state of the membrane and the onset and the intensity of pinocytosis was made in Amoeba proteus. Membrane potential and input resistance was in all instances found to decrease in approximate proportion to the number of channels when pinocytosis was induced by a variety of alkali metal ions at varying pH. Channels began to appear when the membrane was depolarized to -30 mV by the inducer of pinocytosis. With all inducers the maximum pinocytosis was encountered at membrane potentials close to zero. No positive potentials were recorded when the chloride salts of the inducing cations were used. At high concentrations of alkali ions a transient increase of the chloride permeability caused short-lasting hyperolarizations of the membrane. Inhibition of pinocytosis by Ca++ was accompanied by an increase of input resistance and membrane potential. The selectivity of the membrane to different alkali metal ions observed as changes in pinocytosis intensity, membrane potential and input resistance was found to vary with the concentration of the inducer and with the Ca++ concentration of the extracellular solution. Displacement of membrane bound Ca++ appeared to decrease the field strength of charged groups in the membrane altering its selectivity among alkali cations. The formation of pinocytotic channels is suggested to require translocation of Ca++ from the membrane into the cell and would therefore be closely related to the electrical properties of the amoeba.", "contents": "Membrane potential and conductance during pinocytosis induced in Amoeba proteus with alkali metal ions. An investigation of the relationship between the polarized state of the membrane and the onset and the intensity of pinocytosis was made in Amoeba proteus. Membrane potential and input resistance was in all instances found to decrease in approximate proportion to the number of channels when pinocytosis was induced by a variety of alkali metal ions at varying pH. Channels began to appear when the membrane was depolarized to -30 mV by the inducer of pinocytosis. With all inducers the maximum pinocytosis was encountered at membrane potentials close to zero. No positive potentials were recorded when the chloride salts of the inducing cations were used. At high concentrations of alkali ions a transient increase of the chloride permeability caused short-lasting hyperolarizations of the membrane. Inhibition of pinocytosis by Ca++ was accompanied by an increase of input resistance and membrane potential. The selectivity of the membrane to different alkali metal ions observed as changes in pinocytosis intensity, membrane potential and input resistance was found to vary with the concentration of the inducer and with the Ca++ concentration of the extracellular solution. Displacement of membrane bound Ca++ appeared to decrease the field strength of charged groups in the membrane altering its selectivity among alkali cations. The formation of pinocytotic channels is suggested to require translocation of Ca++ from the membrane into the cell and would therefore be closely related to the electrical properties of the amoeba."}
{"id": "PMID:239526", "title": "The blood oxygen transport system. A numerical simulation of capillary-tissue respiratory gas exchange.", "content": "A theoretical model of the process of respiratory gas exchange between capillary and tissue is described, with special reference to the importance of variations in blood properties. The volume of tissue supplied with oxygen from a single vessel, as a function of the blood flowrate (u), hematocrit (h), and 2,3 diphosphoglycerate concentration (DPG), is calculated from a solution to the set of equations governing species distributions in the blood and tissue. The results, which are presented in the form of crossplots of the three blood parameters (u, h, and DPG) at a constant oxygen supply rate, show the possible significance of in vivo variations in the oxygen affinity of hemoglobin as a compensatory mechanism. Of further physiological interest is the sharp increase in venous erythrocyte pH in response to decreases in hematocrit, once the hematocrit is below a certain level. These results, and those relating DPG to hematocrit at constant O2 supply, are consistent with experimental observations of elevated DPG and pH levels in anemic individualts, and the dependence of erythrocyte DPG concentration upon pH.", "contents": "The blood oxygen transport system. A numerical simulation of capillary-tissue respiratory gas exchange. A theoretical model of the process of respiratory gas exchange between capillary and tissue is described, with special reference to the importance of variations in blood properties. The volume of tissue supplied with oxygen from a single vessel, as a function of the blood flowrate (u), hematocrit (h), and 2,3 diphosphoglycerate concentration (DPG), is calculated from a solution to the set of equations governing species distributions in the blood and tissue. The results, which are presented in the form of crossplots of the three blood parameters (u, h, and DPG) at a constant oxygen supply rate, show the possible significance of in vivo variations in the oxygen affinity of hemoglobin as a compensatory mechanism. Of further physiological interest is the sharp increase in venous erythrocyte pH in response to decreases in hematocrit, once the hematocrit is below a certain level. These results, and those relating DPG to hematocrit at constant O2 supply, are consistent with experimental observations of elevated DPG and pH levels in anemic individualts, and the dependence of erythrocyte DPG concentration upon pH."}
{"id": "PMID:239527", "title": "The problem of tissue oxygenation in diabetes mellitus. I. Its relation to the early functional changes in the microcirculation of diabetic subjects.", "content": "The underlying cause leading to the reversible functional changes in the microcirculation of insulin-dependent diabetic subjects early during the disease prior to any clinical signs of retinopathy and nephropathy (functional microangiopathy) is discussed. It is suggested that the initial microvascular dilation observed in diabetics is due to an autoregulatory response to relative tissue hypoxia providing an increased tissue perfusion in order to improve tissue oxygen delivery. Supporting evidence for this suggestion is derived from the findings that diabetics simultaneously may show increased tissue oxygen consumption and decreased ability of the circulating blood to release oxygen to the tissues. The latter defect is likely to be caused by two interrelated factors: 1. an increased proportion of haemoglobin A1c with high oxygen affinity, and 2. difficulties of maintaining a sufficiently high concentration of plasma inorganic phosphate in order to provide an optimal 2,3-diphosphoglycerate (2,3-DPG) content in the erythrocytes. The basal oxygen demand of diabetics may fluctuate even within a few hours dependent upon the state of metabolic control and is increased at times of poor regulation. Hence, diabetics may suffer from innumerable cellular hypoxic injuries, which during the first years of the disease are counteracted in the microcirculation by an autoregulatory response. These microvascular reactions associated with increased plasma permeation may over the years be of major importance for the development of the degenerative microangiopathy in diabetes.", "contents": "The problem of tissue oxygenation in diabetes mellitus. I. Its relation to the early functional changes in the microcirculation of diabetic subjects. The underlying cause leading to the reversible functional changes in the microcirculation of insulin-dependent diabetic subjects early during the disease prior to any clinical signs of retinopathy and nephropathy (functional microangiopathy) is discussed. It is suggested that the initial microvascular dilation observed in diabetics is due to an autoregulatory response to relative tissue hypoxia providing an increased tissue perfusion in order to improve tissue oxygen delivery. Supporting evidence for this suggestion is derived from the findings that diabetics simultaneously may show increased tissue oxygen consumption and decreased ability of the circulating blood to release oxygen to the tissues. The latter defect is likely to be caused by two interrelated factors: 1. an increased proportion of haemoglobin A1c with high oxygen affinity, and 2. difficulties of maintaining a sufficiently high concentration of plasma inorganic phosphate in order to provide an optimal 2,3-diphosphoglycerate (2,3-DPG) content in the erythrocytes. The basal oxygen demand of diabetics may fluctuate even within a few hours dependent upon the state of metabolic control and is increased at times of poor regulation. Hence, diabetics may suffer from innumerable cellular hypoxic injuries, which during the first years of the disease are counteracted in the microcirculation by an autoregulatory response. These microvascular reactions associated with increased plasma permeation may over the years be of major importance for the development of the degenerative microangiopathy in diabetes."}
{"id": "PMID:239528", "title": "The problem of tissue oxygenation in diabetes mellitus.", "content": "In order to study the determining factors for oxygen transport the oxyhaemoglobin dissociation curve (ODC), red cell 2,3-diphosphoglycerate (2,3-DPG), and plasma inorganic phosphate were estimated in insulin-requiring juvenile and adult diabetics in various conditions of metabolic control. 2,3-DPG has been shown to vary much more in diabetics than in normals, depending upon the state of metabolic control. These fluctuations of 2,3-DPG are mediated by variations in plasma inorganic phosphate as indicated by a close correlation. While 2,3-DPG was markedly decreased in diabetic ketoacidosis, it tended to be increased in ambulatory, non-acidotic patients. Since in the non-acidotic patients the oxygen-carrying capacity, i.e. the haemoglobin concentration was simultaneously elevated, these findings suggest the presence of relative tissue hypoxia in diabetes. Both in non-acidotic and in ketoacidotic patients there was a strong correlation between the amount of 2,3-DPG and the P50 at actual pH as an experssion of the oxygen affinity of haemoglobin. In order to guarantee an optimal erythrocyte oxygen release in diabetics the content of red cell 2,3-DPG and plasma inorganic phosphate should be higher than normal.", "contents": "The problem of tissue oxygenation in diabetes mellitus. In order to study the determining factors for oxygen transport the oxyhaemoglobin dissociation curve (ODC), red cell 2,3-diphosphoglycerate (2,3-DPG), and plasma inorganic phosphate were estimated in insulin-requiring juvenile and adult diabetics in various conditions of metabolic control. 2,3-DPG has been shown to vary much more in diabetics than in normals, depending upon the state of metabolic control. These fluctuations of 2,3-DPG are mediated by variations in plasma inorganic phosphate as indicated by a close correlation. While 2,3-DPG was markedly decreased in diabetic ketoacidosis, it tended to be increased in ambulatory, non-acidotic patients. Since in the non-acidotic patients the oxygen-carrying capacity, i.e. the haemoglobin concentration was simultaneously elevated, these findings suggest the presence of relative tissue hypoxia in diabetes. Both in non-acidotic and in ketoacidotic patients there was a strong correlation between the amount of 2,3-DPG and the P50 at actual pH as an experssion of the oxygen affinity of haemoglobin. In order to guarantee an optimal erythrocyte oxygen release in diabetics the content of red cell 2,3-DPG and plasma inorganic phosphate should be higher than normal."}
{"id": "PMID:239529", "title": "In vivo and in vitro phosphorylation of DNA-binding proteins from Escherichia coli.", "content": "A deoxyribonucleoprotein (DNP) complex has been isolated from Escherichia coli cells by chromatography on Sephadex G-200. The DNP complex contains phosphoproteins and the content of phosphorus bound to the DNP protein is 3 times higher than in cytoplasmic proteins not bound to DNA. These results have been confirmed by in vivo (32-P-KH2PO4) and in vitro (32-P-ATP) phosphorylation of E. coli DNA-binding proteins isolated by chromatography on DNA--cellulose.", "contents": "In vivo and in vitro phosphorylation of DNA-binding proteins from Escherichia coli. A deoxyribonucleoprotein (DNP) complex has been isolated from Escherichia coli cells by chromatography on Sephadex G-200. The DNP complex contains phosphoproteins and the content of phosphorus bound to the DNP protein is 3 times higher than in cytoplasmic proteins not bound to DNA. These results have been confirmed by in vivo (32-P-KH2PO4) and in vitro (32-P-ATP) phosphorylation of E. coli DNA-binding proteins isolated by chromatography on DNA--cellulose."}
{"id": "PMID:239535", "title": "Self-association, conformation and binding equilibria of concanavalin A.", "content": "The discovery of distinct intact and fragmented forms of Con A, together with the observation that Con A self-associates near neutrality raises questions that may be important when interpreting experiments concerned with the biological actions of the protein. Do intact and fragmented units have the same affinity for carbohydrate? Do intact and fragmented units differ in conformation? Are all dimeric units of a homologous type or do hybrid dimers consisting of one intact and one fragmented unit also exist? Can all dimeric types self-associate to the tetramer form? Do dimer and tetramer species differ in their affinity for carbohydrate? These questions have been made amenable to investigation by the development of a method which separates intact and fragmented species under conditions which do not cause time-dependent or irreversible changes in protein conformation. It is found that intact dimeric units preferentially associate to the tetramer form. Under appropriate conditions of pH and ionic strength, dimer and tetramer species, and therefore fragmented and intact forms, can be separated by chromatography on Bio Gel P-100. Hybrid dimers are not present in appreciable amounts. Both types of homologous dimers (intact and fragmented) have similar affinity for carbohydrate, but dimer and tetramer species show significant differences. The results of near UV circular dichroism studies indicate that fragmented units possess slightly different conformation than intact units. An ionization-linked conformational transition in Con A does not appear to be linked directly with the self-association of the protein between pH 5 and 7. Ligand-induced changes in the conformation of Con A are now being examined in detail. Pflumm et al. (1971) have shown that occupation of the sugar binding site of Con A results in a perturbation of conformation as revealed by near UV circular dichroism measurements. The perturbation is relatively small and does not result in more than 1-2% increase in the rotational relaxation time (Shinitzky et al., 1973). On the other hand, removal of metal ions causes a hydrodynamic change sufficient to increase the frictional coefficient and to decrease the sedimentation coefficient (S20, w) from 3.98 S to 3.78 S. Differences between the native and the apoprotein conformation are now being examined using fluorescence polarization and the hydrophobic fluorescent probe 1-anilinonaphthalene-8-sulfonate.", "contents": "Self-association, conformation and binding equilibria of concanavalin A. The discovery of distinct intact and fragmented forms of Con A, together with the observation that Con A self-associates near neutrality raises questions that may be important when interpreting experiments concerned with the biological actions of the protein. Do intact and fragmented units have the same affinity for carbohydrate? Do intact and fragmented units differ in conformation? Are all dimeric units of a homologous type or do hybrid dimers consisting of one intact and one fragmented unit also exist? Can all dimeric types self-associate to the tetramer form? Do dimer and tetramer species differ in their affinity for carbohydrate? These questions have been made amenable to investigation by the development of a method which separates intact and fragmented species under conditions which do not cause time-dependent or irreversible changes in protein conformation. It is found that intact dimeric units preferentially associate to the tetramer form. Under appropriate conditions of pH and ionic strength, dimer and tetramer species, and therefore fragmented and intact forms, can be separated by chromatography on Bio Gel P-100. Hybrid dimers are not present in appreciable amounts. Both types of homologous dimers (intact and fragmented) have similar affinity for carbohydrate, but dimer and tetramer species show significant differences. The results of near UV circular dichroism studies indicate that fragmented units possess slightly different conformation than intact units. An ionization-linked conformational transition in Con A does not appear to be linked directly with the self-association of the protein between pH 5 and 7. Ligand-induced changes in the conformation of Con A are now being examined in detail. Pflumm et al. (1971) have shown that occupation of the sugar binding site of Con A results in a perturbation of conformation as revealed by near UV circular dichroism measurements. The perturbation is relatively small and does not result in more than 1-2% increase in the rotational relaxation time (Shinitzky et al., 1973). On the other hand, removal of metal ions causes a hydrodynamic change sufficient to increase the frictional coefficient and to decrease the sedimentation coefficient (S20, w) from 3.98 S to 3.78 S. Differences between the native and the apoprotein conformation are now being examined using fluorescence polarization and the hydrophobic fluorescent probe 1-anilinonaphthalene-8-sulfonate."}
{"id": "PMID:239536", "title": "Studies on the interaction of concanavalin A with glycoproteins.", "content": "Lectins (phytohaemagglutinin) are known to have the unique property of binding with certain specific sugars, polysaccharides and glycoproteins. Although the kinetics of interaction between lectins and sugar have been extensively studied, the binding characteristics of the lectins with various glycoproteins are not well understood. In this laboratory a systematic study has been initiated in relation to the interaction of lectins with glycoproteins. Concanavalin A is known to bind alpha-glucosides, mannosides and biopolymers having these sugar configurations. A galactose binding protein from caster bean has been purified to homogeneity and was found to contain mannose. This lectin was used as the source of glycoprotein for studying its interaction with concanavalin A. This study showed that the interaction is temperature dependent and the dissociation is time and alpha-methyl glucoside concentration dependent. This has led to speculate a model for cell-lectin interaction. Using concanavalin A it has been shown that all the lysosomal enzymes from brain studied were glycoprotein in nature. Moreover, using Sepharose-bound concanavalin A it has been possible to devise a method by which these lysosomal enzymes could be purified considerably. With the knowledge that the interaction between lectin and glycoprotein is not only dependent on the specific sugar present in the glycoprotein, but also on the nature of the glycoprotein it was possible to develop a novel method for immobilizing various glycoprotein enzymes, such as arylsulphatase A, hyaluronidase and glucose oxidase.", "contents": "Studies on the interaction of concanavalin A with glycoproteins. Lectins (phytohaemagglutinin) are known to have the unique property of binding with certain specific sugars, polysaccharides and glycoproteins. Although the kinetics of interaction between lectins and sugar have been extensively studied, the binding characteristics of the lectins with various glycoproteins are not well understood. In this laboratory a systematic study has been initiated in relation to the interaction of lectins with glycoproteins. Concanavalin A is known to bind alpha-glucosides, mannosides and biopolymers having these sugar configurations. A galactose binding protein from caster bean has been purified to homogeneity and was found to contain mannose. This lectin was used as the source of glycoprotein for studying its interaction with concanavalin A. This study showed that the interaction is temperature dependent and the dissociation is time and alpha-methyl glucoside concentration dependent. This has led to speculate a model for cell-lectin interaction. Using concanavalin A it has been shown that all the lysosomal enzymes from brain studied were glycoprotein in nature. Moreover, using Sepharose-bound concanavalin A it has been possible to devise a method by which these lysosomal enzymes could be purified considerably. With the knowledge that the interaction between lectin and glycoprotein is not only dependent on the specific sugar present in the glycoprotein, but also on the nature of the glycoprotein it was possible to develop a novel method for immobilizing various glycoprotein enzymes, such as arylsulphatase A, hyaluronidase and glucose oxidase."}
{"id": "PMID:239537", "title": "An anlysis of the optical titrations of the 430 and 455 NM chromophores of ethyl isocyanide complexes of mammalian hepatic cytochrome P-450.", "content": "A computational method is presented from which one may calculate the pK for the spectral changes of the 430 and 455 mm chromophores of ethyl isocyanide complexes of rabbit and rat liver microsomal cytochrome P-450. For the rat liver protein from control or phenobarital-treated animals, the pK for the loss of the 430 nm absorption is approximately equal to the pK for the gain of the 455 nm absorption, confirming that the two chromophores are in pH equilibrium with one another. For a soluble preparation in which the chromophores exhibit the pH equilbrium property, this equilbrium is also maintained even after the addition of ethyl isocyanide. It is concluded that the appearance of a 430 nm absorption after the addition ethyl isocyanide to reduced cytochrome P-450 does not necessarily represent conversion of the protein to cytochrome P-420.", "contents": "An anlysis of the optical titrations of the 430 and 455 NM chromophores of ethyl isocyanide complexes of mammalian hepatic cytochrome P-450. A computational method is presented from which one may calculate the pK for the spectral changes of the 430 and 455 mm chromophores of ethyl isocyanide complexes of rabbit and rat liver microsomal cytochrome P-450. For the rat liver protein from control or phenobarital-treated animals, the pK for the loss of the 430 nm absorption is approximately equal to the pK for the gain of the 455 nm absorption, confirming that the two chromophores are in pH equilibrium with one another. For a soluble preparation in which the chromophores exhibit the pH equilbrium property, this equilbrium is also maintained even after the addition of ethyl isocyanide. It is concluded that the appearance of a 430 nm absorption after the addition ethyl isocyanide to reduced cytochrome P-450 does not necessarily represent conversion of the protein to cytochrome P-420."}
{"id": "PMID:239540", "title": "Mixed function oxidation and intermediary metabolism: metabolic interdependencies in the liver.", "content": "Both hepatic lipogenesis from glucose and gluconeogenesis from lactate are inhibited by substrates for mixed function oxidation such as aminopyrine. These effects are inducible with phenobarbital pretreatment and absent with a demethylated product of aminopyrine metabolism, aminophenylpyrazolone. The data indicate that an interaction between biosynthesis and drug metabolism occurs in the intact liver cell. In the case of lipogenesis, direct competition for cytosolic NADPH occurs, whereas in the case of gluconeogenesisi, enhanced drug metabolism diverts key intermediates, e.g., malate from glucose synthesis toward NADPH generation. Furthermore, rates of mixed function oxidation were modified following perturbations of intermediary metabolism, e.g., fasting, addition of substrates for glucose synthesis, inhibition of energy metabolism, etc. The data support the hypothesis that in the presence of sufficiently high concentrations of substrate and oxygen, the rate-limiting step for mixed function oxidation in the intact cell is supply of NADPH.", "contents": "Mixed function oxidation and intermediary metabolism: metabolic interdependencies in the liver. Both hepatic lipogenesis from glucose and gluconeogenesis from lactate are inhibited by substrates for mixed function oxidation such as aminopyrine. These effects are inducible with phenobarbital pretreatment and absent with a demethylated product of aminopyrine metabolism, aminophenylpyrazolone. The data indicate that an interaction between biosynthesis and drug metabolism occurs in the intact liver cell. In the case of lipogenesis, direct competition for cytosolic NADPH occurs, whereas in the case of gluconeogenesisi, enhanced drug metabolism diverts key intermediates, e.g., malate from glucose synthesis toward NADPH generation. Furthermore, rates of mixed function oxidation were modified following perturbations of intermediary metabolism, e.g., fasting, addition of substrates for glucose synthesis, inhibition of energy metabolism, etc. The data support the hypothesis that in the presence of sufficiently high concentrations of substrate and oxygen, the rate-limiting step for mixed function oxidation in the intact cell is supply of NADPH."}
{"id": "PMID:239546", "title": "Comparison of methods to study enzyme induction in man.", "content": "A combination of several in vivo parameters has been applied in male healthy volunteers to test the suitability of these parameters to indicate enzyme induction in man: Urinary excretion of D-glucaric acid and 6 beta-hydroxycortisol, activity of serum gamma-glut amyltranspeptidase, and pharmacokinetics of aminopyrine respond significantly to phenobarbital treatment. Glucaric acid excretion is enhanced about 7-fold. Its response to induction overcomes the large individual and inter-individual variations which exist in the untreated state for glucaric acid excretion and the other parameters applied, as well. Total body clearance of aminopyrine as obtained after an oral test dose increases more than twofold from 251 to 551 ml/min upon phenobarbital treatment. This arises from increases in both the elimination constant and the apparent volume of distribution, as well. Urinary excretion of aminoantipyrine during 24 hr is about doubled, whereas the elimination of acetyl-aminotipyrine is not much affected. 6 beta-hydroxycortisol excretion in urine and activity of serum gamma-glutamyltranspeptidase are significantly augmented to about 150% of control values. Half life times of phenobarbital measured after termination of treatment are in normal range, suggesting no self-induction of phenobarbital metabolism. Because of the complexity of drug metabolizing enzymes only a combination of different parameters reliably indicates alterations in this enzyme system by inducing agents.", "contents": "Comparison of methods to study enzyme induction in man. A combination of several in vivo parameters has been applied in male healthy volunteers to test the suitability of these parameters to indicate enzyme induction in man: Urinary excretion of D-glucaric acid and 6 beta-hydroxycortisol, activity of serum gamma-glut amyltranspeptidase, and pharmacokinetics of aminopyrine respond significantly to phenobarbital treatment. Glucaric acid excretion is enhanced about 7-fold. Its response to induction overcomes the large individual and inter-individual variations which exist in the untreated state for glucaric acid excretion and the other parameters applied, as well. Total body clearance of aminopyrine as obtained after an oral test dose increases more than twofold from 251 to 551 ml/min upon phenobarbital treatment. This arises from increases in both the elimination constant and the apparent volume of distribution, as well. Urinary excretion of aminoantipyrine during 24 hr is about doubled, whereas the elimination of acetyl-aminotipyrine is not much affected. 6 beta-hydroxycortisol excretion in urine and activity of serum gamma-glutamyltranspeptidase are significantly augmented to about 150% of control values. Half life times of phenobarbital measured after termination of treatment are in normal range, suggesting no self-induction of phenobarbital metabolism. Because of the complexity of drug metabolizing enzymes only a combination of different parameters reliably indicates alterations in this enzyme system by inducing agents."}
{"id": "PMID:239549", "title": "[Study of Brazilian agricultural workers. A medico-socio-psychological study].", "content": "The general state of health of native Brazilian agricultural workers - a total of 750 people from 3 different plantations in the States of Paran\u00e1 and Saso Paulo - was examined. The main interest of this study war centred on infectious and parasitic diseases, nutritional conditions as well as social, intellectual factors. Apart from the high number of cases of helminthiasis, amounting to 80%, the general state of health of the examined subjects was found to be good - indeed better than that of a hypothetical, comparable group of Europeans. Except for the Chagas' disease, by which 5% of the test subjects were afflicted, infectious diseases posed no serious problems. There was no case of malnutrition. The relatively lower intellectual level can not be attributed to any heriditary factor, and could definitely be improved by proper schooling. Corrective measures: Chagas: Since brick houses have replaced the wooden ones for several years, new infections are unlikely. Helminthiasis: In addition to the anthelminthic treatment, sanitary prophylactic measures should be taken. Social-intellectual factors: The following points should be emphasized: elementary schooling on the plantations; teaching at intermediary level; sewing and cooking courses; general hygience.", "contents": "[Study of Brazilian agricultural workers. A medico-socio-psychological study]. The general state of health of native Brazilian agricultural workers - a total of 750 people from 3 different plantations in the States of Paran\u00e1 and Saso Paulo - was examined. The main interest of this study war centred on infectious and parasitic diseases, nutritional conditions as well as social, intellectual factors. Apart from the high number of cases of helminthiasis, amounting to 80%, the general state of health of the examined subjects was found to be good - indeed better than that of a hypothetical, comparable group of Europeans. Except for the Chagas' disease, by which 5% of the test subjects were afflicted, infectious diseases posed no serious problems. There was no case of malnutrition. The relatively lower intellectual level can not be attributed to any heriditary factor, and could definitely be improved by proper schooling. Corrective measures: Chagas: Since brick houses have replaced the wooden ones for several years, new infections are unlikely. Helminthiasis: In addition to the anthelminthic treatment, sanitary prophylactic measures should be taken. Social-intellectual factors: The following points should be emphasized: elementary schooling on the plantations; teaching at intermediary level; sewing and cooking courses; general hygience."}
{"id": "PMID:239550", "title": "[Simple method for obtaining Toxocara canis antigen for the indirect immunofluorescence technic].", "content": "A simple method for the preparation of Toxocara canis antigen for the indirect immunofluorescent test is described: Embryonated Toxocara eggs are treated for 12 hours at room temperature with a 1:1 mixture of 2% NaHO and sodium hypochlorite (NaClO) solution with a concentration of 2% free chlorine in order to remove the outer layers of the egg shells. The larvae which are still enclosed in the lipid membrane are freed by mild ultrasonic treatment. Thereafter, the suspension of larvae is washed and purified in a modified Baermann apparatus. In this way large numbers of larvae in pure suspension were gained and used for the production of frozen sections for the indirect immunofluorescent test. Rabbits and mice experimentally infected with embryonated Toxocara canis eggs showed a positive serological reaction (titers between 1/10 to 1/320) in this test with Toxocara larvae as antigen, while in uninfected control animals no antibodies could be detected. The larval antigen exhibited only a weak cross reaction with sera of animals infected with Ascaris suum eggs.", "contents": "[Simple method for obtaining Toxocara canis antigen for the indirect immunofluorescence technic]. A simple method for the preparation of Toxocara canis antigen for the indirect immunofluorescent test is described: Embryonated Toxocara eggs are treated for 12 hours at room temperature with a 1:1 mixture of 2% NaHO and sodium hypochlorite (NaClO) solution with a concentration of 2% free chlorine in order to remove the outer layers of the egg shells. The larvae which are still enclosed in the lipid membrane are freed by mild ultrasonic treatment. Thereafter, the suspension of larvae is washed and purified in a modified Baermann apparatus. In this way large numbers of larvae in pure suspension were gained and used for the production of frozen sections for the indirect immunofluorescent test. Rabbits and mice experimentally infected with embryonated Toxocara canis eggs showed a positive serological reaction (titers between 1/10 to 1/320) in this test with Toxocara larvae as antigen, while in uninfected control animals no antibodies could be detected. The larval antigen exhibited only a weak cross reaction with sera of animals infected with Ascaris suum eggs."}
{"id": "PMID:239551", "title": "The esterase patterns in the ovaries and the embryonated eggs of Aedes aegypti L.", "content": "The esterases of Aedes aegypti were studied in the ovary before and during a gonotrophic cycle and also in fully embryonated eggs by means of disc electrophoresis. During oogenesis no significacant changes can be observed besides a marked increase in the total esterase activity. A different esterase pattern is found in eggs after embryogenesis. The electrophoretic mobility of some esterase bands is highly increased in the ovary compared to other organs. One esterase fraction in the ovary and two in the fertilized egg were identified as acetylcholinesterases. All other enzymes are carboxylesterases.  The results are compared to those of previous authors and are discussed in view of possible functions of esterases during reproduction.", "contents": "The esterase patterns in the ovaries and the embryonated eggs of Aedes aegypti L. The esterases of Aedes aegypti were studied in the ovary before and during a gonotrophic cycle and also in fully embryonated eggs by means of disc electrophoresis. During oogenesis no significacant changes can be observed besides a marked increase in the total esterase activity. A different esterase pattern is found in eggs after embryogenesis. The electrophoretic mobility of some esterase bands is highly increased in the ovary compared to other organs. One esterase fraction in the ovary and two in the fertilized egg were identified as acetylcholinesterases. All other enzymes are carboxylesterases.  The results are compared to those of previous authors and are discussed in view of possible functions of esterases during reproduction."}
{"id": "PMID:239552", "title": "Trypanosomes and experimental trypanosomaisis in East African bats.", "content": "Using the haematocrit centrifuge technique, four hundred and twenty-seven bats from East Africa were examined for trypanosome infections. Approximately 21% of the bats were found to be infected. The infection rate varied from zero to 73.3%. No trypanosome was found in fruit-eating bats (Megachiroptera). Three species of trypanosomes were found in insect-eating bats (Microchiroptera), none of the trypanosome was infective to mice or rats. The trypanosomes encountered in the survey were Trypanosoma (Schizotrypanum) vespertilionis, T. (Megatrypanum) heybergi, and T. (M). mpapuense. New descriptions based on abundant materials are given for each of the species. Trypanosoma rhodesiense and T. brucei produced a much more chronic infection in insect-eating bats (Tadarida condylura) than in mice. Since it is known that some species of Glossina feed on bats, we raised the possibility of insect-eating bats as potential reservoirs of these trypanosomes. In experiments fruit-eating bats seem to be much more susceptible to T. brucei than the insect-eating bats. T. vivax is not infective to bats.", "contents": "Trypanosomes and experimental trypanosomaisis in East African bats. Using the haematocrit centrifuge technique, four hundred and twenty-seven bats from East Africa were examined for trypanosome infections. Approximately 21% of the bats were found to be infected. The infection rate varied from zero to 73.3%. No trypanosome was found in fruit-eating bats (Megachiroptera). Three species of trypanosomes were found in insect-eating bats (Microchiroptera), none of the trypanosome was infective to mice or rats. The trypanosomes encountered in the survey were Trypanosoma (Schizotrypanum) vespertilionis, T. (Megatrypanum) heybergi, and T. (M). mpapuense. New descriptions based on abundant materials are given for each of the species. Trypanosoma rhodesiense and T. brucei produced a much more chronic infection in insect-eating bats (Tadarida condylura) than in mice. Since it is known that some species of Glossina feed on bats, we raised the possibility of insect-eating bats as potential reservoirs of these trypanosomes. In experiments fruit-eating bats seem to be much more susceptible to T. brucei than the insect-eating bats. T. vivax is not infective to bats."}
{"id": "PMID:239555", "title": "The effect of purine and pyrimidine analogues and virazole on adenovirus replication.", "content": "The multiplication of adenovirus 19 in HeLa cells was inhibited by various purine and pyrimidine analogues and by virazole.  The formation of infectious virus and of capsid proteins (haemagglutin, group-specific complement-fixing antigen) was inhibited to the same degree, while the viral cytopathic effect (CPE) was not inhibited.  The reversibility of the inhibition after removal of the substances was more complete for purine than for pyrimidine analogues.  The inhibition was counteracted by simulataneous addition of the corresponding nucleosides.  Adenosine was more effected than guanosine against purine analogues; both were partially effective against virazole, but none of them against arabinofuranosyladenine.  The time-dependence of inhibition, the ensuing eclipse period after removal of the inhibitors, and the successive application of two inhibitors led to the conclusion that most of them affect the viral multiplication mainly by inhibition of DNA synthesis.  Azacytidine inhibits the synthesis of structural proteins as well.", "contents": "The effect of purine and pyrimidine analogues and virazole on adenovirus replication. The multiplication of adenovirus 19 in HeLa cells was inhibited by various purine and pyrimidine analogues and by virazole.  The formation of infectious virus and of capsid proteins (haemagglutin, group-specific complement-fixing antigen) was inhibited to the same degree, while the viral cytopathic effect (CPE) was not inhibited.  The reversibility of the inhibition after removal of the substances was more complete for purine than for pyrimidine analogues.  The inhibition was counteracted by simulataneous addition of the corresponding nucleosides.  Adenosine was more effected than guanosine against purine analogues; both were partially effective against virazole, but none of them against arabinofuranosyladenine.  The time-dependence of inhibition, the ensuing eclipse period after removal of the inhibitors, and the successive application of two inhibitors led to the conclusion that most of them affect the viral multiplication mainly by inhibition of DNA synthesis.  Azacytidine inhibits the synthesis of structural proteins as well."}
{"id": "PMID:239556", "title": "Two mechanisms of interferon production by leukocytes from immunized animals.", "content": "Leukocytes from animals immunized against measles were treated with different doses of interferon and 5-fluorouracil. Under the influence of virus-inducer, two mechanisms of interferon production were realized in the leukocytes: early after immunization (1 day), pre-existing interferon was released; subsequently (4 days) de novo interferon production was started. Interferons induced in cultures of leukocytes from animals at 1 and 4 days after immunization were shown to differ in some physico-chemical properties.", "contents": "Two mechanisms of interferon production by leukocytes from immunized animals. Leukocytes from animals immunized against measles were treated with different doses of interferon and 5-fluorouracil. Under the influence of virus-inducer, two mechanisms of interferon production were realized in the leukocytes: early after immunization (1 day), pre-existing interferon was released; subsequently (4 days) de novo interferon production was started. Interferons induced in cultures of leukocytes from animals at 1 and 4 days after immunization were shown to differ in some physico-chemical properties."}
{"id": "PMID:239557", "title": "Double-stranded complex of polyguanylic and polycytidylic acids and its antiviral activity in tissue culture.", "content": "The antiviral activity and conditions of formation of the most active double-stranded complexes of synthetic homopolynucleotides, polyriboguanylic and polyribocytidylic acids, were studied on the model of primary trypsinized chick embryo cells and RNA-containing viruses. The (poly G).(poly C) complex was very active against the viruses tested; their replication in cell cultures was inhibited completely. The antiviral activity of the (poly G).(poly C) complex increased markedly in the presence of diethylaminoethyl- (DEAE-) dextran. After treatment with 1 mug/ml of (poly G). (poly C) for 1 hour in the presence of 100 mug/ml DEAE-dextran, the cell sheet remained protected for 5-7 days. Preparations of (poly G).(poly C) obtained under optimal conditions were as active as (poly I).(poly C) complexes and exceeded them markedly in the level of the therapeutic index which under the present experimental conditions was 5-10 times 10(3) for (poly G).(poly C). Highly purified homopolymers with sufficiently high molecular weight must be used for production of active and stable (poly G).(poly C) complexes.", "contents": "Double-stranded complex of polyguanylic and polycytidylic acids and its antiviral activity in tissue culture. The antiviral activity and conditions of formation of the most active double-stranded complexes of synthetic homopolynucleotides, polyriboguanylic and polyribocytidylic acids, were studied on the model of primary trypsinized chick embryo cells and RNA-containing viruses. The (poly G).(poly C) complex was very active against the viruses tested; their replication in cell cultures was inhibited completely. The antiviral activity of the (poly G).(poly C) complex increased markedly in the presence of diethylaminoethyl- (DEAE-) dextran. After treatment with 1 mug/ml of (poly G). (poly C) for 1 hour in the presence of 100 mug/ml DEAE-dextran, the cell sheet remained protected for 5-7 days. Preparations of (poly G).(poly C) obtained under optimal conditions were as active as (poly I).(poly C) complexes and exceeded them markedly in the level of the therapeutic index which under the present experimental conditions was 5-10 times 10(3) for (poly G).(poly C). Highly purified homopolymers with sufficiently high molecular weight must be used for production of active and stable (poly G).(poly C) complexes."}
{"id": "PMID:239558", "title": "Neuraminidase activity of influenza virus-infected cells: localization and properties.", "content": "Infection of chick embryo cell (CEC) cultures with influenza virus results in the appearance of neuraminidase activity lost by the cells as a result of cultivation.  Neuraminidase activity is associated mainly with the lysomal cell fraction.  Different distribution of neuraminidase activity in lysosomes with various densities, different reaction to sodium ethylene diamine tetracetate (EDTA) and differenct optimal pH suggest that at early stages of viral infection the cell enzyme is activated and by the 7th hour of infection viral neuraminidase is synthesized.", "contents": "Neuraminidase activity of influenza virus-infected cells: localization and properties. Infection of chick embryo cell (CEC) cultures with influenza virus results in the appearance of neuraminidase activity lost by the cells as a result of cultivation.  Neuraminidase activity is associated mainly with the lysomal cell fraction.  Different distribution of neuraminidase activity in lysosomes with various densities, different reaction to sodium ethylene diamine tetracetate (EDTA) and differenct optimal pH suggest that at early stages of viral infection the cell enzyme is activated and by the 7th hour of infection viral neuraminidase is synthesized."}
{"id": "PMID:239559", "title": "Biophysical properties of coronavirus strain OC 43.", "content": "Coronavirus OC 43 from suckling mouse brains was subjected to sucrose density gradient centrifugation.  Maxima of complement fixing (CF) activities occurred in the ribosomal (density 1.14) and mitochondrial (density 1.19) fraction which contained incomplete, damaged virus particles.  The haemagglutinating (HA) activity was associated with the microsomal soluble protein fraction displayed no antigenic activity.  The isolated purified virus proved to be very unstable.", "contents": "Biophysical properties of coronavirus strain OC 43. Coronavirus OC 43 from suckling mouse brains was subjected to sucrose density gradient centrifugation.  Maxima of complement fixing (CF) activities occurred in the ribosomal (density 1.14) and mitochondrial (density 1.19) fraction which contained incomplete, damaged virus particles.  The haemagglutinating (HA) activity was associated with the microsomal soluble protein fraction displayed no antigenic activity.  The isolated purified virus proved to be very unstable."}
{"id": "PMID:239560", "title": "Further virological and clinical investigations on the attenuated E5\"14\" virus from the tick-borne excephalitis complex.", "content": "A total of 22 persons, given a single intramuscular dose of 3.1 times 10(6) newborn mouse ic LD50/ml of the E5\"14\" virus (stored for 26 months at 4 degrees C in lyophilized state), were subjected to rigorous clinical, clinical-laboratory and virological investigations. Clinical observations and laboratory tests (blood and cerebrospinal fluid cytology and biochemistry) revealed no ill-effects or deviations attributable to the immunization procedure. After administration of the immunizing dose, no viraemia was detected and specific seroconversions from negativity to positivity were found after 9 weeks in 73-82% of the subjects, using different tick-borne encephalitis (western subtype) viruses in the virus neutralization experiments. The results obtained seem to give increased confidence in the further use of this attenuated virus clone with strictly defined characteristics.", "contents": "Further virological and clinical investigations on the attenuated E5\"14\" virus from the tick-borne excephalitis complex. A total of 22 persons, given a single intramuscular dose of 3.1 times 10(6) newborn mouse ic LD50/ml of the E5\"14\" virus (stored for 26 months at 4 degrees C in lyophilized state), were subjected to rigorous clinical, clinical-laboratory and virological investigations. Clinical observations and laboratory tests (blood and cerebrospinal fluid cytology and biochemistry) revealed no ill-effects or deviations attributable to the immunization procedure. After administration of the immunizing dose, no viraemia was detected and specific seroconversions from negativity to positivity were found after 9 weeks in 73-82% of the subjects, using different tick-borne encephalitis (western subtype) viruses in the virus neutralization experiments. The results obtained seem to give increased confidence in the further use of this attenuated virus clone with strictly defined characteristics."}
{"id": "PMID:239561", "title": "A modified plaque method for arboviruses on plastic panels.", "content": "Autoclavable culture media containing an increased (10---15-fold)concentration of succinate buffer permit a comparitively long-term cultivation of cells in free gas exchange with the atmosphere.  Based on them, an economical technique of plaque titration of arboviruses on plastic panels with methylcellulose overlay was developed.  With seven arboviruses of three different groups and three cell lines (CV-1, PS and PK), the method proved sufficiently sensitive as compared with titrations in mice or tube cell cultures and suitable for plaque reduction tests.", "contents": "A modified plaque method for arboviruses on plastic panels. Autoclavable culture media containing an increased (10---15-fold)concentration of succinate buffer permit a comparitively long-term cultivation of cells in free gas exchange with the atmosphere.  Based on them, an economical technique of plaque titration of arboviruses on plastic panels with methylcellulose overlay was developed.  With seven arboviruses of three different groups and three cell lines (CV-1, PS and PK), the method proved sufficiently sensitive as compared with titrations in mice or tube cell cultures and suitable for plaque reduction tests."}
{"id": "PMID:239562", "title": "Morphology of A/WSN influenza virus-infected chick embryo cells.", "content": "A/WSN (H0N1) influenza virus-infected chick embryo cells (CEC) attained a swollen central region 4 hours post infection (p.i.), different from the elongated uninfected cell. From 6 hours p.i. of CEC an increasing number of approximately 100-120 nm, round protrusions were observed by scanning and transmission electron microscopy on the cell membrane, which was smooth on the uninfected cell. At 48 hours p.i. a great number of protrusions were observed on the cell; in addition, there were a number of holes or invaginations in the membranes of the infected cells indicating cell destruction.", "contents": "Morphology of A/WSN influenza virus-infected chick embryo cells. A/WSN (H0N1) influenza virus-infected chick embryo cells (CEC) attained a swollen central region 4 hours post infection (p.i.), different from the elongated uninfected cell. From 6 hours p.i. of CEC an increasing number of approximately 100-120 nm, round protrusions were observed by scanning and transmission electron microscopy on the cell membrane, which was smooth on the uninfected cell. At 48 hours p.i. a great number of protrusions were observed on the cell; in addition, there were a number of holes or invaginations in the membranes of the infected cells indicating cell destruction."}
{"id": "PMID:239563", "title": "Interferon-hyporesponsiveness in mice in connection with dose interval and site of administration of Newcastle disease virus. Reflexion in serum complement levels.", "content": "Intraperitoneal administration of Newcastle disease virus (NDV) resulted in enhanced serum levels of complement not accompanied by an increase of interferon levels, when measured at 24 hours' intervals. On the other hand, intravenous injection of NDV caused a drop of complement levels of short duration with an accompanying increase of interferon levels. Hyporeactivity to induction of serum interferon could not be achieved by intraperitoneal administration of NDV, but an incomplete hyporeactivity could be achieved by intravenous administration of NDV. It might be assumed that production of interferon in mice occurs in different separated compartments depending on the route of inoculation of the inducer.", "contents": "Interferon-hyporesponsiveness in mice in connection with dose interval and site of administration of Newcastle disease virus. Reflexion in serum complement levels. Intraperitoneal administration of Newcastle disease virus (NDV) resulted in enhanced serum levels of complement not accompanied by an increase of interferon levels, when measured at 24 hours' intervals. On the other hand, intravenous injection of NDV caused a drop of complement levels of short duration with an accompanying increase of interferon levels. Hyporeactivity to induction of serum interferon could not be achieved by intraperitoneal administration of NDV, but an incomplete hyporeactivity could be achieved by intravenous administration of NDV. It might be assumed that production of interferon in mice occurs in different separated compartments depending on the route of inoculation of the inducer."}
{"id": "PMID:239564", "title": "Isolation and identification of group B arboviruses from the blood of birds captured in Czechoslovakia.", "content": "Three West Nile (WN) virus strains were isolated from the blood of birds (Tringa ochropus, Vanellus vanellus and Streptopenia turtur) captured in south Slovakia.  One strain of tick-borne encephalitis (TE) virus was isolated from the blood of Tringa ochropus captured in south Moravia.", "contents": "Isolation and identification of group B arboviruses from the blood of birds captured in Czechoslovakia. Three West Nile (WN) virus strains were isolated from the blood of birds (Tringa ochropus, Vanellus vanellus and Streptopenia turtur) captured in south Slovakia.  One strain of tick-borne encephalitis (TE) virus was isolated from the blood of Tringa ochropus captured in south Moravia."}
{"id": "PMID:239565", "title": "Antibody to lymphocytic choriomeningitis virus in children with congenital hydrocephalus.", "content": "Antibody to lymphocytic choriomeningitis (LCM) virus was found by the indirect immunofluorescence (IF) technique in high titres in 9 out of 28 children with congenital hydrocephalus and in moderate titres in 6 mothers of these seropositive children.  It is suggested that LCM virus or a closely related virus infecting the foetus in utero may play a role in the aetiopathogenesis of some cases of congenital hydrocephalus.", "contents": "Antibody to lymphocytic choriomeningitis virus in children with congenital hydrocephalus. Antibody to lymphocytic choriomeningitis (LCM) virus was found by the indirect immunofluorescence (IF) technique in high titres in 9 out of 28 children with congenital hydrocephalus and in moderate titres in 6 mothers of these seropositive children.  It is suggested that LCM virus or a closely related virus infecting the foetus in utero may play a role in the aetiopathogenesis of some cases of congenital hydrocephalus."}
{"id": "PMID:239570", "title": "Interaction of plasma membranes with influenza virus. V. Changes in creatine phosphokinase activity.", "content": "A decrease in creatine phosphokinase (CPK) activity was observed in plasma membranes (PM) treated with native A/WSN influenza virus but not in PM treated with heat-inactivated virus. The decrease in CPK activity depended on the amount of virus added to PM, on the pH of the medium and on the quality of the isolated PM. It was evident already after 10 minutes of incubation at 37 degrees C. The possible mechanism of the inhibition of the CPK activity and the relation to changes in adenosine triphosphatase (ATPase) activity and to fusion are discussed.", "contents": "Interaction of plasma membranes with influenza virus. V. Changes in creatine phosphokinase activity. A decrease in creatine phosphokinase (CPK) activity was observed in plasma membranes (PM) treated with native A/WSN influenza virus but not in PM treated with heat-inactivated virus. The decrease in CPK activity depended on the amount of virus added to PM, on the pH of the medium and on the quality of the isolated PM. It was evident already after 10 minutes of incubation at 37 degrees C. The possible mechanism of the inhibition of the CPK activity and the relation to changes in adenosine triphosphatase (ATPase) activity and to fusion are discussed."}
{"id": "PMID:239571", "title": "Excision of bromodeoxyuridine from T4-DNA by an antimutator polymerase of T4 phage.", "content": "With gene-43 (DNA polymerase)-ts-mutants of T4 phage, L98 (mutator) and CB121 (antimutator), and the T4 wild type, double labelling of DNA was carried out with (H3)-bromodeoxyuridine (BUdR) and (C14)-thymidine (TdR). Experiments on (C14) TdR for DNA synthesis measurement in the presence of BUdR offered evidence of the ability of the CB121 mutant to excise BUdR from the DNA. This effect took place only at increased temperature. As distinct from DNA synthesis of the host, all T4 phages used preferred TdR rather than BUdR for net synthesis.", "contents": "Excision of bromodeoxyuridine from T4-DNA by an antimutator polymerase of T4 phage. With gene-43 (DNA polymerase)-ts-mutants of T4 phage, L98 (mutator) and CB121 (antimutator), and the T4 wild type, double labelling of DNA was carried out with (H3)-bromodeoxyuridine (BUdR) and (C14)-thymidine (TdR). Experiments on (C14) TdR for DNA synthesis measurement in the presence of BUdR offered evidence of the ability of the CB121 mutant to excise BUdR from the DNA. This effect took place only at increased temperature. As distinct from DNA synthesis of the host, all T4 phages used preferred TdR rather than BUdR for net synthesis."}
{"id": "PMID:239572", "title": "Adenosine triphosphate phosphoydrolase activity associated with purified parainfluenza type 3 virions.", "content": "An adenosine triphosphate phosphohydrolase associated with purified parainfluenza type 3 virions has been characterized. It hydrolyzed ATP to ADP and AMP when activated with Mg-2+ ions. Using Ca-2+ the production of ADP was inhibited but not that of AMP. Neither K+ NOR Na+ ions were required for the expression of maximal activity. Ouabain had no inhibitory effect on enzyme activity even at 10-3M. After exposure of virus preparations to Tween 20, enzyme activity was not affected. A linear relationship between enzyme activity and concentration of virus was observed.", "contents": "Adenosine triphosphate phosphoydrolase activity associated with purified parainfluenza type 3 virions. An adenosine triphosphate phosphohydrolase associated with purified parainfluenza type 3 virions has been characterized. It hydrolyzed ATP to ADP and AMP when activated with Mg-2+ ions. Using Ca-2+ the production of ADP was inhibited but not that of AMP. Neither K+ NOR Na+ ions were required for the expression of maximal activity. Ouabain had no inhibitory effect on enzyme activity even at 10-3M. After exposure of virus preparations to Tween 20, enzyme activity was not affected. A linear relationship between enzyme activity and concentration of virus was observed."}
{"id": "PMID:239573", "title": "Purification of influenza viruses on wide-pore glass columns.", "content": "Influenza viruses of different serotypes were purified by gel filtration on wide-pore glass. The virus thus purfied retained completely its haemagglutinating activity and infectivity, and by one purification cycle at least 99% of ballast proteins were removed.", "contents": "Purification of influenza viruses on wide-pore glass columns. Influenza viruses of different serotypes were purified by gel filtration on wide-pore glass. The virus thus purfied retained completely its haemagglutinating activity and infectivity, and by one purification cycle at least 99% of ballast proteins were removed."}
{"id": "PMID:239574", "title": "Properties of the cholera phage PL 163/10.", "content": "Vibrio cholerae phage PL 163/10, belonging to Mukherjee's group I, gave clear plaques with surrounding halos of overall diameters varying between 1 to 4 mm when plated on a lawn of host V. cholerae OGAWA 154. It was fairly stable in the PH range 6-11. Its thermal inactivation was characterised by half lives of 39, 12, 4.5 and 1.0 minutes at 55, 60, 65 and 70 degree C respectively. The thermodynamic parameters deltaH, deltaF and deltaS were determined at these temperatures. The phange was resistant in vitro to sodium deoxycholate, trytrypsin, chloroform, robonuclease, deoxyribonuclease, Tris, Tris + EDTA, Tris + lysozyme and phosphate buffer but rapidly inactivated by sodium lauryl sulfate. Adsorption of this phage was biphasic. Intracelllular growth of the PL 163/10 phage was characterised by an eclipse period of 13 minutes, latent period of 31 minutes, rise period of 29 minutes and an average burst size of about 10 PFU/cell. This phage possessed a hexagonal head 106 plus or minus 18 x x 740 plus or minus 27 A without any tail structure.", "contents": "Properties of the cholera phage PL 163/10. Vibrio cholerae phage PL 163/10, belonging to Mukherjee's group I, gave clear plaques with surrounding halos of overall diameters varying between 1 to 4 mm when plated on a lawn of host V. cholerae OGAWA 154. It was fairly stable in the PH range 6-11. Its thermal inactivation was characterised by half lives of 39, 12, 4.5 and 1.0 minutes at 55, 60, 65 and 70 degree C respectively. The thermodynamic parameters deltaH, deltaF and deltaS were determined at these temperatures. The phange was resistant in vitro to sodium deoxycholate, trytrypsin, chloroform, robonuclease, deoxyribonuclease, Tris, Tris + EDTA, Tris + lysozyme and phosphate buffer but rapidly inactivated by sodium lauryl sulfate. Adsorption of this phage was biphasic. Intracelllular growth of the PL 163/10 phage was characterised by an eclipse period of 13 minutes, latent period of 31 minutes, rise period of 29 minutes and an average burst size of about 10 PFU/cell. This phage possessed a hexagonal head 106 plus or minus 18 x x 740 plus or minus 27 A without any tail structure."}
{"id": "PMID:239575", "title": "Cytogenetic study of the continuous RH cell line and its clones with a different susceptibility to measles virus.", "content": "A comparative karyological study was carried out on the RH continuous line of human embryo kidney cells and its 3 clones differing in their sensitivity to the cytopathic effect (CPE) of vaccine measles virus (L-16 strain). The clonal variants studied were shown to have different karyotypes and their sensitivities to be genetically determined. There was a correlation between the rate of appearance and the pattern of the CPE and the percentage of cells in which a set of 33 chromosomes and a high level of polyploidy were combined.", "contents": "Cytogenetic study of the continuous RH cell line and its clones with a different susceptibility to measles virus. A comparative karyological study was carried out on the RH continuous line of human embryo kidney cells and its 3 clones differing in their sensitivity to the cytopathic effect (CPE) of vaccine measles virus (L-16 strain). The clonal variants studied were shown to have different karyotypes and their sensitivities to be genetically determined. There was a correlation between the rate of appearance and the pattern of the CPE and the percentage of cells in which a set of 33 chromosomes and a high level of polyploidy were combined."}
{"id": "PMID:239576", "title": "A live vaccine against tick-borne encephalitis: integrated studies. I. Basic properties and behaviour of the E5 \"14\" Clone (Langat virus).", "content": "The course of plaque segregation from the Langat E5 strain of the E5 \"14\" clone is described. The virus, displaying an ic+ sc s plus or minus t e u s character, reproduced at 35 and 37, but not at 39 degree C. In subcutaneously (sc) inoculated monkeys, viraemia lasted for 2--4 days without detectable central nervous system (CNS) involvement. In sc inoculated 8--10 g mice, the infection was manifested only by a transient trace viraemia, but caused a marked resistance against challenge with virulent tick-borne encephalitis (TE) viruses, protection indices being 5.7--6.7. Pathogenetic investigations in challenged, live virus-immunized mice showed no signs of a marked productive infection except of a booster effect.", "contents": "A live vaccine against tick-borne encephalitis: integrated studies. I. Basic properties and behaviour of the E5 \"14\" Clone (Langat virus). The course of plaque segregation from the Langat E5 strain of the E5 \"14\" clone is described. The virus, displaying an ic+ sc s plus or minus t e u s character, reproduced at 35 and 37, but not at 39 degree C. In subcutaneously (sc) inoculated monkeys, viraemia lasted for 2--4 days without detectable central nervous system (CNS) involvement. In sc inoculated 8--10 g mice, the infection was manifested only by a transient trace viraemia, but caused a marked resistance against challenge with virulent tick-borne encephalitis (TE) viruses, protection indices being 5.7--6.7. Pathogenetic investigations in challenged, live virus-immunized mice showed no signs of a marked productive infection except of a booster effect."}
{"id": "PMID:239577", "title": "A live vaccine against tick-borne encephalitis; integrated studies, H. Histopathology of mice peripherally immunized with E5 \"14\" virus and challenged with virulent virus.", "content": "Histopathological changes in the central nervous and lymphoid systems were semiquantitatively analyzed in subadult mice (M) peripherally immunized with the live, highly attenuated E5 \"14\" virus from the tick-born encephalitis (TE) complex and in immunized M subjected to virulent challenge. The E5 \"14\" clone possesses an exceedingly restricted neuroinvasivity. A study of the sc marker, refined and extended by microscopic examinations seems to present a more relevant approach for comparative investigations on TE virus virulence. Morphological findings in immunized M given immunosuppressive doses of cyclophosphamide (CPA) suggest that the high efficiency of live vaccines may be related to the prolonged antigenic stimulation.", "contents": "A live vaccine against tick-borne encephalitis; integrated studies, H. Histopathology of mice peripherally immunized with E5 \"14\" virus and challenged with virulent virus. Histopathological changes in the central nervous and lymphoid systems were semiquantitatively analyzed in subadult mice (M) peripherally immunized with the live, highly attenuated E5 \"14\" virus from the tick-born encephalitis (TE) complex and in immunized M subjected to virulent challenge. The E5 \"14\" clone possesses an exceedingly restricted neuroinvasivity. A study of the sc marker, refined and extended by microscopic examinations seems to present a more relevant approach for comparative investigations on TE virus virulence. Morphological findings in immunized M given immunosuppressive doses of cyclophosphamide (CPA) suggest that the high efficiency of live vaccines may be related to the prolonged antigenic stimulation."}
{"id": "PMID:239578", "title": "A live vaccine against tick-born encephalitis: integrated studies. III. Response of man to a single dose of the E5 \"14\" clone (Langat virus).", "content": "The clinical and immunological events in volunteers following administration of 5 and 6 dex newborn mouse intracerebral LD5O (NmicLD5O) of the E5 \"14\" virus clone, segregated from the Langat TP21 E5 strain (tick-borne encephalitis-TE-complex) and propagated in 7 days old SPF chick embryos, are reported. The experimental vaccine, containing the cloned virus, carrying a set of genetic markers of an ic(+) sc s(+/-) t e u (s) N character, caused in volunteers no clinically recognizable effects, but elicited an immune response in them, as determined in PS-cell culture neutralization tests with various TE (western and eastern subtype) strains. In all vaccines, given the virus intramuscularly, seroconversions from negativity to positivity were observed, with antibody titres ranging from 4-128. The parenteral virus administration was superior to the oral route.", "contents": "A live vaccine against tick-born encephalitis: integrated studies. III. Response of man to a single dose of the E5 \"14\" clone (Langat virus). The clinical and immunological events in volunteers following administration of 5 and 6 dex newborn mouse intracerebral LD5O (NmicLD5O) of the E5 \"14\" virus clone, segregated from the Langat TP21 E5 strain (tick-borne encephalitis-TE-complex) and propagated in 7 days old SPF chick embryos, are reported. The experimental vaccine, containing the cloned virus, carrying a set of genetic markers of an ic(+) sc s(+/-) t e u (s) N character, caused in volunteers no clinically recognizable effects, but elicited an immune response in them, as determined in PS-cell culture neutralization tests with various TE (western and eastern subtype) strains. In all vaccines, given the virus intramuscularly, seroconversions from negativity to positivity were observed, with antibody titres ranging from 4-128. The parenteral virus administration was superior to the oral route."}
{"id": "PMID:239579", "title": "Passive immunity against Jun\u00edn virus in mice.", "content": "Passive immunity, naturally acquired from immune mothers or artificially induced by the administration of homologous hyperimmune serum, conferred on suckling mice a high degree of resistance against infection with Jun\u00edn virus. Maternal antibodies in the circulating blood of the young were not detectable in the first days after birth, but rised rapidly from the 8th to the 20th day of lactation. By cross-foster nursing experiments it was shown that the greater part of the transmission of passive immunity occurred after birth, although there was transmission of a significant, though small part, before birth. The virus passage from mothers to offspring was excluded, since Jun\u00edn virus was not recovered from brains, livers, spleens and kidneys of uninfected young, born from infected mothers.", "contents": "Passive immunity against Jun\u00edn virus in mice. Passive immunity, naturally acquired from immune mothers or artificially induced by the administration of homologous hyperimmune serum, conferred on suckling mice a high degree of resistance against infection with Jun\u00edn virus. Maternal antibodies in the circulating blood of the young were not detectable in the first days after birth, but rised rapidly from the 8th to the 20th day of lactation. By cross-foster nursing experiments it was shown that the greater part of the transmission of passive immunity occurred after birth, although there was transmission of a significant, though small part, before birth. The virus passage from mothers to offspring was excluded, since Jun\u00edn virus was not recovered from brains, livers, spleens and kidneys of uninfected young, born from infected mothers."}
{"id": "PMID:239580", "title": "The presence of interferon and type A immunoglobulins in the nasopharyngeal secretions of volunteers immunized with an inactivated influenza vaccine.", "content": "The presence of interferon and type A immunoglobulins (IgA) was followed up in the nasopharyngeal washings collected from volunteers immunized intranasally with an inactivated influenza vaccine [strain A/Rom 1/73 (H3N2)]. Interferon was detected 24 hours after vaccine administration, its incidence being similar to that in the course of acute infection. Intranasal administration of inactivated influenza vaccine stimulated the production of secretory IgA in 3 of 10 samples collected 12 days after vaccination. At the same time, IgA were found in 4 samples collected before vaccination, and inhibited in certain cases the stimulation of interferon synthesis. The practical importance of the route of influenza vaccine administration is discussed.", "contents": "The presence of interferon and type A immunoglobulins in the nasopharyngeal secretions of volunteers immunized with an inactivated influenza vaccine. The presence of interferon and type A immunoglobulins (IgA) was followed up in the nasopharyngeal washings collected from volunteers immunized intranasally with an inactivated influenza vaccine [strain A/Rom 1/73 (H3N2)]. Interferon was detected 24 hours after vaccine administration, its incidence being similar to that in the course of acute infection. Intranasal administration of inactivated influenza vaccine stimulated the production of secretory IgA in 3 of 10 samples collected 12 days after vaccination. At the same time, IgA were found in 4 samples collected before vaccination, and inhibited in certain cases the stimulation of interferon synthesis. The practical importance of the route of influenza vaccine administration is discussed."}
{"id": "PMID:239581", "title": "Erythrocyte-sensitizing substance from Rickettsia Canadia.", "content": "Erythrocyte-sensitizing substance (ESS) extracted from Rickettsia canada reacted with homologous sera as well as with sera containing antibodies against Rickettsia prowazeki, but did not react with sera containing antibodies against Rickettsia conori or Coxiella burneti. This finding confirms the antigenic relatedness of R. canada to the typhus rickettsiae group.", "contents": "Erythrocyte-sensitizing substance from Rickettsia Canadia. Erythrocyte-sensitizing substance (ESS) extracted from Rickettsia canada reacted with homologous sera as well as with sera containing antibodies against Rickettsia prowazeki, but did not react with sera containing antibodies against Rickettsia conori or Coxiella burneti. This finding confirms the antigenic relatedness of R. canada to the typhus rickettsiae group."}
{"id": "PMID:239586", "title": "Mechanisms of variability of vertebrate virus populations.", "content": "A number of factors favouring the persistence and accumulation of mutant virus particles are active in virus populations with a complicated genetic structure. The latter circumstance permits to apply the concept of genetic load to these virus populations. Complication of the genetic structure permits a virus population to make a qualitative leap in the struggle for existence.", "contents": "Mechanisms of variability of vertebrate virus populations. A number of factors favouring the persistence and accumulation of mutant virus particles are active in virus populations with a complicated genetic structure. The latter circumstance permits to apply the concept of genetic load to these virus populations. Complication of the genetic structure permits a virus population to make a qualitative leap in the struggle for existence."}
{"id": "PMID:239588", "title": "Alterations in myocardial hydrogen ion concentration after temporary coronary occlusion: a sign of irreversible cell damage.", "content": "Alterations of hydrogen ion (H+) concentration in the myocardium of 60 cats were determined before release of coronary ligation of 30, 45, 60, 90 or 180 minutes' duration, or 5, 30 and 90 minutes after release of the occlusion, by pressing pH indicator paper on unfixed frozen heart sections. The H+ concentration had clearly increased (pH less than 6.0) in a transmural extension in the left ventricle before release of the coronary ligature. This elevated H+ concentration persisted some time in the subendocardial region despite release of the coronary occlusion, thus proving that the so-called no reflow phenomenon exists in involved myocardium after temporary coronary occlusion. A diminished H+ concentration (pH 7.4) was found in the border zone between the acid-reacting area and the normal muscle when the coronary occlusion lasted 180 minutes before release of the ligature or 30 minutes after release of the occlusion when the previous period of temporary occlusion had been longer than 30 minutes. Although areas manifesting an acid reaction vanished or diminished in size after release of coronary occlusion, the extent of alkaline-reacting zones showed no reduction in size, and muscle cell necrosis developed in these alkaline-reacting areas. It is assumed therefore that an alkaline reaction of the myocardium is an early sign of irreversible muscle cell damage.", "contents": "Alterations in myocardial hydrogen ion concentration after temporary coronary occlusion: a sign of irreversible cell damage. Alterations of hydrogen ion (H+) concentration in the myocardium of 60 cats were determined before release of coronary ligation of 30, 45, 60, 90 or 180 minutes' duration, or 5, 30 and 90 minutes after release of the occlusion, by pressing pH indicator paper on unfixed frozen heart sections. The H+ concentration had clearly increased (pH less than 6.0) in a transmural extension in the left ventricle before release of the coronary ligature. This elevated H+ concentration persisted some time in the subendocardial region despite release of the coronary occlusion, thus proving that the so-called no reflow phenomenon exists in involved myocardium after temporary coronary occlusion. A diminished H+ concentration (pH 7.4) was found in the border zone between the acid-reacting area and the normal muscle when the coronary occlusion lasted 180 minutes before release of the ligature or 30 minutes after release of the occlusion when the previous period of temporary occlusion had been longer than 30 minutes. Although areas manifesting an acid reaction vanished or diminished in size after release of coronary occlusion, the extent of alkaline-reacting zones showed no reduction in size, and muscle cell necrosis developed in these alkaline-reacting areas. It is assumed therefore that an alkaline reaction of the myocardium is an early sign of irreversible muscle cell damage."}
{"id": "PMID:239589", "title": "Comparison of several activated partial thromboplastin time methods.", "content": "Activated partial thromboplastin times (APTT's) performed with a semi-automated electrical-conductivity type of clot timer on plasmas from patients with hepatic disease and intravascular coagulation, and on warfarin or heparin therapy, were significantly lower than when done on the same plasmas with either a manual optical method or an automated optical-endpoint instrument. Results of APTT's done on normal plasmas by the three methods were not significantly different. Substitution of different activator-phospholipid reagents resulted in some variability in results, but these differences were less than those between the different done with both the electrical clot timer and the automated optical instrument on prepared plasmas containing 5.0 or 1.0% of factor II, V, VIII, IX, OR X revealed shorter times with the electrical clot timer only in the case of factor II- and factor V-deficient plasmas. APTT's done on normal plasmas to which 0.1 or 0.3 units per ml. of heparin had been added vitro also were shorter with the electrical clot itmer than the automatic optical instrument. Prothrombin times done on normal and abnormal control plasmas and on a series of plasmas from patients on warfarin therapy showed no significant difference between the two methods.", "contents": "Comparison of several activated partial thromboplastin time methods. Activated partial thromboplastin times (APTT's) performed with a semi-automated electrical-conductivity type of clot timer on plasmas from patients with hepatic disease and intravascular coagulation, and on warfarin or heparin therapy, were significantly lower than when done on the same plasmas with either a manual optical method or an automated optical-endpoint instrument. Results of APTT's done on normal plasmas by the three methods were not significantly different. Substitution of different activator-phospholipid reagents resulted in some variability in results, but these differences were less than those between the different done with both the electrical clot timer and the automated optical instrument on prepared plasmas containing 5.0 or 1.0% of factor II, V, VIII, IX, OR X revealed shorter times with the electrical clot timer only in the case of factor II- and factor V-deficient plasmas. APTT's done on normal plasmas to which 0.1 or 0.3 units per ml. of heparin had been added vitro also were shorter with the electrical clot itmer than the automatic optical instrument. Prothrombin times done on normal and abnormal control plasmas and on a series of plasmas from patients on warfarin therapy showed no significant difference between the two methods."}
{"id": "PMID:239591", "title": "The \"otitis-prone\" condition.", "content": "We studied the incidence of exudative otitis media in 488 patients followed up from birth. Forty-nine percent (240) of the patients had their initial episode of otitis media in the first year of life and only 12% (56) in the second year of life. Thereafter, the incidence decreased steadily. Patients having six or more episodes of otitis media before age 6 were termed \"otitis prone\". Fifty-seven such patients were observed and this condition was found to be significantly related to the onset of otitis media in the first year of life and to the pneumococcal cause of the initial episode.", "contents": "The \"otitis-prone\" condition. We studied the incidence of exudative otitis media in 488 patients followed up from birth. Forty-nine percent (240) of the patients had their initial episode of otitis media in the first year of life and only 12% (56) in the second year of life. Thereafter, the incidence decreased steadily. Patients having six or more episodes of otitis media before age 6 were termed \"otitis prone\". Fifty-seven such patients were observed and this condition was found to be significantly related to the onset of otitis media in the first year of life and to the pneumococcal cause of the initial episode."}
{"id": "PMID:239592", "title": "The adverse effect of chocolate on lower esophageal sphincter pressure.", "content": "Decreased lower esophageal sphincter (LES) pressure after ingestion of chocolate has been previously noted. We have further evaluated the effect of chocolate on the known ability of gastric alkalinization or bethanechol to increase LES tone. 9 normal subjects were studied using an infused open-tip recording system. Pressure was monitored for a 15-min basal period, and for 60 min after ingestion of 120 ml of chocolate syrup either alone or with the concurrent administration of commercial antacid, oral bethanechol, or subcutaneous bethanechol. After chocolate ingestion, mean basal LES pressure of 14.6 +/- 1.1 (+/-SEM) mm Hg decreased significantly (P less than 0.01) to 7.9 +/- 1.3 mm Hg. An identical LES response occurred when antacid was given with the chocolate dose. Oral bethanechol (25 mg) and chocolate together resulted in lesser decreases in LES pressure. Subcutaneous bethanechol (5 mg) and chocolate produced significant increases (P less than 0.05) in sphincter pressure, although of lesser magnitude than reported with bethanechol alone. These results indicate that the adverse effect of chocolate on the LES is not reversed by gastric alkalinization and suggest that bethanechol in sufficient dose may overcome chocolate-induced decreases in LES pressure.", "contents": "The adverse effect of chocolate on lower esophageal sphincter pressure. Decreased lower esophageal sphincter (LES) pressure after ingestion of chocolate has been previously noted. We have further evaluated the effect of chocolate on the known ability of gastric alkalinization or bethanechol to increase LES tone. 9 normal subjects were studied using an infused open-tip recording system. Pressure was monitored for a 15-min basal period, and for 60 min after ingestion of 120 ml of chocolate syrup either alone or with the concurrent administration of commercial antacid, oral bethanechol, or subcutaneous bethanechol. After chocolate ingestion, mean basal LES pressure of 14.6 +/- 1.1 (+/-SEM) mm Hg decreased significantly (P less than 0.01) to 7.9 +/- 1.3 mm Hg. An identical LES response occurred when antacid was given with the chocolate dose. Oral bethanechol (25 mg) and chocolate together resulted in lesser decreases in LES pressure. Subcutaneous bethanechol (5 mg) and chocolate produced significant increases (P less than 0.05) in sphincter pressure, although of lesser magnitude than reported with bethanechol alone. These results indicate that the adverse effect of chocolate on the LES is not reversed by gastric alkalinization and suggest that bethanechol in sufficient dose may overcome chocolate-induced decreases in LES pressure."}
{"id": "PMID:239593", "title": "Report and characterization of a new variant, EB, of human red cell acid phosphatase.", "content": "A new variant phenotype of human red cell acid phosphatase, designated EB, was discovered in a male during a survey of blood donors from Copenhagen, Denmark. Electrophoretically, the variant revealed the two isozymes corresponding to the B type as well as two fast moving anodic isozymes. The enzyme activity and thermostability were found to be higher than in any earlier reported type. Isoelectric focusing of the variant type indicated that the isoelectric point of the variant enzyme is lower than in the common types.", "contents": "Report and characterization of a new variant, EB, of human red cell acid phosphatase. A new variant phenotype of human red cell acid phosphatase, designated EB, was discovered in a male during a survey of blood donors from Copenhagen, Denmark. Electrophoretically, the variant revealed the two isozymes corresponding to the B type as well as two fast moving anodic isozymes. The enzyme activity and thermostability were found to be higher than in any earlier reported type. Isoelectric focusing of the variant type indicated that the isoelectric point of the variant enzyme is lower than in the common types."}
{"id": "PMID:239594", "title": "Intropin (dopamine hydrochloride) intravenous admixture compatibility. Part 1: stability with common intravenous fluids.", "content": "The stability of dopamine hydrochloride (Intropin) in several large-volume parenteral solutions was studied. Admixtures of dopamine were assayed by colorimetric and chromatographic procedures. Admixtures (800 mug dopamine per ml) in the following intravenous fluids in glass bottles at pH 6.85 or below were found to be chemically and physically stable for at least 48 hours at room temperature: dextrose 5%, dextrose 5% and sodium chloride 0.9%, 5% dextrose in 0.45% sodium chloride, dextrose 5% in lactated Ringer's solution, lactated Ringer's injection, 0.9% sodium chloride, 1/6 molar sodium lactate, and 20% mannitol. The admixture of dopamine in 5% dextrose was stable for a minimum of seven days at 5 C. A 5% dextrose-dopamine admixture in a polyvinylchloride bag was stable for at least 24 hours at room temperature. The admixture of dopamine in 5% sodium bicarbonate solution produced an unstable solution of pH 8.20. A chemical and physical change (development of a pink color) was observed in this admixture. It is recommended that dopamine not be added to 5% sodium bicarbonate solution or any alkaline intravenous solution.", "contents": "Intropin (dopamine hydrochloride) intravenous admixture compatibility. Part 1: stability with common intravenous fluids. The stability of dopamine hydrochloride (Intropin) in several large-volume parenteral solutions was studied. Admixtures of dopamine were assayed by colorimetric and chromatographic procedures. Admixtures (800 mug dopamine per ml) in the following intravenous fluids in glass bottles at pH 6.85 or below were found to be chemically and physically stable for at least 48 hours at room temperature: dextrose 5%, dextrose 5% and sodium chloride 0.9%, 5% dextrose in 0.45% sodium chloride, dextrose 5% in lactated Ringer's solution, lactated Ringer's injection, 0.9% sodium chloride, 1/6 molar sodium lactate, and 20% mannitol. The admixture of dopamine in 5% dextrose was stable for a minimum of seven days at 5 C. A 5% dextrose-dopamine admixture in a polyvinylchloride bag was stable for at least 24 hours at room temperature. The admixture of dopamine in 5% sodium bicarbonate solution produced an unstable solution of pH 8.20. A chemical and physical change (development of a pink color) was observed in this admixture. It is recommended that dopamine not be added to 5% sodium bicarbonate solution or any alkaline intravenous solution."}
{"id": "PMID:239595", "title": "Evaluation of a hospital controlled substances distribution system.", "content": "The distribution and control system for controlled drugs at a 500-bed hospital was evaluated. The time requirements of the system for pharmacy and nursing, the drug control procedures used, and the income and expenses of the system were evaluated. It was concluded that the system appears to offer full accountability, but it makes a heavy time demand on pharmacy and nursing. Time requirements could be reduced through a computerized system or by use of a certificate of disposition form that incorporates a charge voucher.", "contents": "Evaluation of a hospital controlled substances distribution system. The distribution and control system for controlled drugs at a 500-bed hospital was evaluated. The time requirements of the system for pharmacy and nursing, the drug control procedures used, and the income and expenses of the system were evaluated. It was concluded that the system appears to offer full accountability, but it makes a heavy time demand on pharmacy and nursing. Time requirements could be reduced through a computerized system or by use of a certificate of disposition form that incorporates a charge voucher."}
{"id": "PMID:239596", "title": "Drug diffusion and bioavailability: tetracycline metallic chelation.", "content": "The effects of chelation on the in vitro diffusion rate of tetracycline at variable pH values and concentrations was studied. A two-compartment diffusion cell using a semipermeable cellophane membrane was used to determine diffusion rates. Tetracycline in solution was mixed with aluminum, magnesium, copper, calcium and cobalt ions and analyzed by ultraviolet spectrophotometry. Diffusion rates were determined at pH 1, 5.5 and 8. Tetracycline chelate formation is pH-dependent. The diffusion rate of tetracycline chelates is concentration-dependent and is reduced even if the chelate is water soluble.", "contents": "Drug diffusion and bioavailability: tetracycline metallic chelation. The effects of chelation on the in vitro diffusion rate of tetracycline at variable pH values and concentrations was studied. A two-compartment diffusion cell using a semipermeable cellophane membrane was used to determine diffusion rates. Tetracycline in solution was mixed with aluminum, magnesium, copper, calcium and cobalt ions and analyzed by ultraviolet spectrophotometry. Diffusion rates were determined at pH 1, 5.5 and 8. Tetracycline chelate formation is pH-dependent. The diffusion rate of tetracycline chelates is concentration-dependent and is reduced even if the chelate is water soluble."}
{"id": "PMID:239597", "title": "Evaluation of bacteriological transport systems.", "content": "Seven commercially manufactured bacteriological transport systems, including Culturette, Trans-Cul (with Stuart and Amies), Handiswab, Securline (with Amies and Amies without charcoal) and Culture Caddy, were evaluated to determine whether these systems were capable of maintaining the viability and constant numbers of mixtures of hardy, fastidious and anaerobic organisms over 72 hours at 25C and 4C. The results of the study indicated that if specimens are maintained in transport systems at 25C they should be cultured at four hours to minimize loss of viability and to assure accurate quantitation. No one transport system excelled over the other for maintenance of cultures at room temperature. Most organisms survived well in all of the transport systems for 72 hours when refrigerated.", "contents": "Evaluation of bacteriological transport systems. Seven commercially manufactured bacteriological transport systems, including Culturette, Trans-Cul (with Stuart and Amies), Handiswab, Securline (with Amies and Amies without charcoal) and Culture Caddy, were evaluated to determine whether these systems were capable of maintaining the viability and constant numbers of mixtures of hardy, fastidious and anaerobic organisms over 72 hours at 25C and 4C. The results of the study indicated that if specimens are maintained in transport systems at 25C they should be cultured at four hours to minimize loss of viability and to assure accurate quantitation. No one transport system excelled over the other for maintenance of cultures at room temperature. Most organisms survived well in all of the transport systems for 72 hours when refrigerated."}
{"id": "PMID:239598", "title": "Prolonged fetal bradycardia with recovery--its significance and outcome.", "content": "bradycardia lasting more than 21/2 minutes with a decrease in FHR of more than 30 b.p.m. were observed in the course of 15 monitored labors. The mean fetal pH during the 20 minutes following the bradycardia (early recovery) was significantly less than the mean pH obtained 30 minutes or more after the bradycardia (late recovery). Various types of periodic heart rate changes were observed during the early recovery period but few persisted into late recovery. Vaginal delivery occurred in 13 of 15 patients. Two cesarean sections were performed for indications unrelated to the prolonged bradycardia. The 5 minute Apgar score of all 15 neonates was 7 or greater.", "contents": "Prolonged fetal bradycardia with recovery--its significance and outcome. bradycardia lasting more than 21/2 minutes with a decrease in FHR of more than 30 b.p.m. were observed in the course of 15 monitored labors. The mean fetal pH during the 20 minutes following the bradycardia (early recovery) was significantly less than the mean pH obtained 30 minutes or more after the bradycardia (late recovery). Various types of periodic heart rate changes were observed during the early recovery period but few persisted into late recovery. Vaginal delivery occurred in 13 of 15 patients. Two cesarean sections were performed for indications unrelated to the prolonged bradycardia. The 5 minute Apgar score of all 15 neonates was 7 or greater."}
{"id": "PMID:239599", "title": "Renal excretion of N'1-methylnicotinamide in the rat.", "content": "The renal excretion of N'1-methylnicotinamide (NMN) was studied in the rat.  Renal clearance experiments clearly demonstrated that: 1) NMN is secreted; 2)a tubularmaximum (Tm), 7 mumol/min per kg, could be reached; and 3)NMN secretion is inhibitedby a competitive inhibitor, mepiperphenidol.  In free-flow micropuncture experiments, animals were infused with plasma concentrations of NMN ABOVE Tm; the TF/P NMNto TF/P inblin ratio for proximal and distal samples was 2.34 and 2.28, respectively, indicating that NMN is secreted in the proximal tubules and is not secreted orreabsorbed in the distal tubules.  This finding was further confirmed by intratubularmicroinjections of ['14C]NMN into rats.  In diuretic animals approxiamately 10%of the NMN injected into early proximal tubules was reabsorbed, but no reabsorption could be detected after distal injections.  The nondiuretic animals showed no significant reabsorption of NMN.  It was concluded that NMN transport is a carrier-mediated process and that reabsorption, if it occurs, plays only a minor role.", "contents": "Renal excretion of N'1-methylnicotinamide in the rat. The renal excretion of N'1-methylnicotinamide (NMN) was studied in the rat.  Renal clearance experiments clearly demonstrated that: 1) NMN is secreted; 2)a tubularmaximum (Tm), 7 mumol/min per kg, could be reached; and 3)NMN secretion is inhibitedby a competitive inhibitor, mepiperphenidol.  In free-flow micropuncture experiments, animals were infused with plasma concentrations of NMN ABOVE Tm; the TF/P NMNto TF/P inblin ratio for proximal and distal samples was 2.34 and 2.28, respectively, indicating that NMN is secreted in the proximal tubules and is not secreted orreabsorbed in the distal tubules.  This finding was further confirmed by intratubularmicroinjections of ['14C]NMN into rats.  In diuretic animals approxiamately 10%of the NMN injected into early proximal tubules was reabsorbed, but no reabsorption could be detected after distal injections.  The nondiuretic animals showed no significant reabsorption of NMN.  It was concluded that NMN transport is a carrier-mediated process and that reabsorption, if it occurs, plays only a minor role."}
{"id": "PMID:239600", "title": "Peritubular pH and PCO'2 in renal tubular acidification.", "content": "The influence of peritubular capillary pH and PCO'2 on renal tubular acidification was studied in rats by luminal and peritubular perfusion techniques.  Luminal stopped-flow microperfusions were carried out with bicarbonate or alkaline phosphate solutions and luminal pH continuously measured by antimony micorelectrodes.  Peritubular calpillary microperfusions were carried out with mammalian Ringer solution kept at different pH and PCO'2.  The acidification process was assessed in terms of 1)maximal pH differences, 2)rates of pH change, and 3)rates of bicarbinate reabsorption or H'+ ion secretion.  During peritubular perfusions at physiological pH and PCO'2 tubular  acidifying capacity was maintained at near-normal levels.  Perfusingcapillaries at high pH and low PCO'2, especially with bicarbonate Ringer, acidification was markedly depressed; it was moderately reduced at a peritubular pH of 5.6.  At a capillary pH of 7.4, acidification was similiar at low and physiological PCO'2and enhanced at elevated PCO'2.  Systemic respiratory acidosis enhanced acidification in the proximal tubule, but reduced it in distal segments.", "contents": "Peritubular pH and PCO'2 in renal tubular acidification. The influence of peritubular capillary pH and PCO'2 on renal tubular acidification was studied in rats by luminal and peritubular perfusion techniques.  Luminal stopped-flow microperfusions were carried out with bicarbonate or alkaline phosphate solutions and luminal pH continuously measured by antimony micorelectrodes.  Peritubular calpillary microperfusions were carried out with mammalian Ringer solution kept at different pH and PCO'2.  The acidification process was assessed in terms of 1)maximal pH differences, 2)rates of pH change, and 3)rates of bicarbinate reabsorption or H'+ ion secretion.  During peritubular perfusions at physiological pH and PCO'2 tubular  acidifying capacity was maintained at near-normal levels.  Perfusingcapillaries at high pH and low PCO'2, especially with bicarbonate Ringer, acidification was markedly depressed; it was moderately reduced at a peritubular pH of 5.6.  At a capillary pH of 7.4, acidification was similiar at low and physiological PCO'2and enhanced at elevated PCO'2.  Systemic respiratory acidosis enhanced acidification in the proximal tubule, but reduced it in distal segments."}
{"id": "PMID:239601", "title": "Phospholipase A2 in experimental hypertension.", "content": "An assay method has been developed to measure phospholipase A2 (PLA2) in ratserum and to study the possible role of this enzyme in experimental hypertension.  Experiments with rat serum following 48 h of bilateral nephrectomy indicated a decrease inPLA2 activity, suggesting that kidneys might be playing an important role in regulating serum PLA2 activity and that kidneys might be a source of this enzyme.  Experiments with renal hypertensive rats, spontaneously hypertensive rats, and rats receiving a low-salt diet demonstrated that a decrease in PLA2 activity was found only in those conditions in which elevated plasma renin activity was accompanied by elevated blood pressure.  When elevated plasma renin activity was not accompanied by elevated blood pressure, serum PLA2 activity was unchanged.  These observations represent the first biochemical separation between conditions of elevated plasma renin activity without an increase in blood pressure and conditions of elevated plasma renin activity with an increasein blood pressure.", "contents": "Phospholipase A2 in experimental hypertension. An assay method has been developed to measure phospholipase A2 (PLA2) in ratserum and to study the possible role of this enzyme in experimental hypertension.  Experiments with rat serum following 48 h of bilateral nephrectomy indicated a decrease inPLA2 activity, suggesting that kidneys might be playing an important role in regulating serum PLA2 activity and that kidneys might be a source of this enzyme.  Experiments with renal hypertensive rats, spontaneously hypertensive rats, and rats receiving a low-salt diet demonstrated that a decrease in PLA2 activity was found only in those conditions in which elevated plasma renin activity was accompanied by elevated blood pressure.  When elevated plasma renin activity was not accompanied by elevated blood pressure, serum PLA2 activity was unchanged.  These observations represent the first biochemical separation between conditions of elevated plasma renin activity without an increase in blood pressure and conditions of elevated plasma renin activity with an increasein blood pressure."}
{"id": "PMID:239602", "title": "Effect of hyperventilation on dynamics of cerebral energy metabolism.", "content": "Hypocapnia of moderate and extreme degree (Paco2 21.1 and 13.5 torr, respectively)was induced by hyperventilation in rats subjected to the closed system of Lowry inorder to evaluate the effects on utilization rate of cerebral energy metabolites.  The tissue levels of high-energy phosphates and calculated intracellular pH did not change, whereas glucose, pyruvate, and lactate increased significantly.  The La/Pyratio and NADH/NAD-+ RATIO BOTH INCREASED IN PROPORTION TO THE DEGREE OF HYPOCAPNIA. Utilization rates of glucose, glycogen, and ATP were all significantly reduced by hypocapnia, whereas the utilization rate of phosphocreatine was increased.  The rate oftotal high-energy phosphate use was also diminished in proportion to the degree of hypocapnia.  The constant value of the energy charge (0.94 plus or minus 0.01) indicates that the energy production rate might also be reduced by hyperventilation; thus the intermediate metabolics and substrates increased.  It is concluded that extreme hypocapnia reduces the rate of cerebral energy metabolism significantly.", "contents": "Effect of hyperventilation on dynamics of cerebral energy metabolism. Hypocapnia of moderate and extreme degree (Paco2 21.1 and 13.5 torr, respectively)was induced by hyperventilation in rats subjected to the closed system of Lowry inorder to evaluate the effects on utilization rate of cerebral energy metabolites.  The tissue levels of high-energy phosphates and calculated intracellular pH did not change, whereas glucose, pyruvate, and lactate increased significantly.  The La/Pyratio and NADH/NAD-+ RATIO BOTH INCREASED IN PROPORTION TO THE DEGREE OF HYPOCAPNIA. Utilization rates of glucose, glycogen, and ATP were all significantly reduced by hypocapnia, whereas the utilization rate of phosphocreatine was increased.  The rate oftotal high-energy phosphate use was also diminished in proportion to the degree of hypocapnia.  The constant value of the energy charge (0.94 plus or minus 0.01) indicates that the energy production rate might also be reduced by hyperventilation; thus the intermediate metabolics and substrates increased.  It is concluded that extreme hypocapnia reduces the rate of cerebral energy metabolism significantly."}
{"id": "PMID:239603", "title": "Patterns of Plasmodium vivax recurrence in a high-incidence coastal area of El Salvador, C. A.", "content": "During field studies carried out in 1971, 1972 and 1973 in a highly malarious coastal area of El Salvador, it was possible to collect information on the patterns of Plasmodium vivax parasite occurrence in a large number of infected individuals. In most of the persons who had experienced a malaria attack during the high transmission period in June, July, August and September, renewed activity occurred 5 to 8 months later, during the low transmission season the next year. Subsequent activity in these same cases occurred after intervals of about 4 to 9 weeks in duration. On epidemiologic grounds, and on the basis of the life patterns of the El Salvador P. vivax strains demonstrated in previous studies in volunteers, this renewal of activity probably represents the occurrence of relapses rather than new infections. This pattern is similar to the \"temperature zone\" strains of P. vivax, where initial relapses occur after prolonged periods, followed by subsequent relapses after much shorter intervals of inactivity. This type of relapse pattern in a tropical area may enhance the survival of the parasite through a prolonged period of vector inactivity, such as the long dry season experienced in El Salvador.", "contents": "Patterns of Plasmodium vivax recurrence in a high-incidence coastal area of El Salvador, C. A. During field studies carried out in 1971, 1972 and 1973 in a highly malarious coastal area of El Salvador, it was possible to collect information on the patterns of Plasmodium vivax parasite occurrence in a large number of infected individuals. In most of the persons who had experienced a malaria attack during the high transmission period in June, July, August and September, renewed activity occurred 5 to 8 months later, during the low transmission season the next year. Subsequent activity in these same cases occurred after intervals of about 4 to 9 weeks in duration. On epidemiologic grounds, and on the basis of the life patterns of the El Salvador P. vivax strains demonstrated in previous studies in volunteers, this renewal of activity probably represents the occurrence of relapses rather than new infections. This pattern is similar to the \"temperature zone\" strains of P. vivax, where initial relapses occur after prolonged periods, followed by subsequent relapses after much shorter intervals of inactivity. This type of relapse pattern in a tropical area may enhance the survival of the parasite through a prolonged period of vector inactivity, such as the long dry season experienced in El Salvador."}
{"id": "PMID:239604", "title": "California encephalitis virus prevalence throughout the Yukon Territory, 1971-1974.", "content": "California encephalitis (CE) virus (snowshoe hare subtype) was isolated from 1 of 38 pools comprising 970 unengorged female Aedes canadensis mosquitoes and from 3 of 152 pools containing 5,676 A. communis mosquitoes which were collected in the Yukon Territory, Canada between latitudes 61 and 66 degrees N during June and July 1974. During four summers 1971 through 1974, this virus was recovered from 26 of 648 pools derived from 30,686 mosquitoes of 4 species. Isolation of CE virus from 1 of 109 pools of Aedes sp. larvae collected during May 1974 suggests maintenance of this virus over winter by transovarial transfer. Infectivity has been maintained in Culiseta inornata mosquitoes which were held continuously at 32 degrees F for 138 days. Neutralizing antibodies to CE virus were detected in 705 of 4,913 (14%) mammals collected during summers 1971 through 1974, including 430 of 1,076 (40%) snowshoe hares (Lepus americanus), 266 of 3,610 (7%) ground squirrels (Citellus undulatus) and 9 of 227 (4%) red squirrels (Tamiasciurus hudsonicus).", "contents": "California encephalitis virus prevalence throughout the Yukon Territory, 1971-1974. California encephalitis (CE) virus (snowshoe hare subtype) was isolated from 1 of 38 pools comprising 970 unengorged female Aedes canadensis mosquitoes and from 3 of 152 pools containing 5,676 A. communis mosquitoes which were collected in the Yukon Territory, Canada between latitudes 61 and 66 degrees N during June and July 1974. During four summers 1971 through 1974, this virus was recovered from 26 of 648 pools derived from 30,686 mosquitoes of 4 species. Isolation of CE virus from 1 of 109 pools of Aedes sp. larvae collected during May 1974 suggests maintenance of this virus over winter by transovarial transfer. Infectivity has been maintained in Culiseta inornata mosquitoes which were held continuously at 32 degrees F for 138 days. Neutralizing antibodies to CE virus were detected in 705 of 4,913 (14%) mammals collected during summers 1971 through 1974, including 430 of 1,076 (40%) snowshoe hares (Lepus americanus), 266 of 3,610 (7%) ground squirrels (Citellus undulatus) and 9 of 227 (4%) red squirrels (Tamiasciurus hudsonicus)."}
{"id": "PMID:239605", "title": "Nephrotic syndrome in Schistosomiasis mansoni complicated by chronic salmonellosis.", "content": "Thirteen patients with concomitant chronic salmonellosis and schistosomiasis and with the nephrotic syndrome were studied. Of the seven patients' sera examined, all had markedly low complement C3 and near normal C4 levels. This indirectly suggests an active role of Salmonella endotoxin in the etiology of the nephrosis.", "contents": "Nephrotic syndrome in Schistosomiasis mansoni complicated by chronic salmonellosis. Thirteen patients with concomitant chronic salmonellosis and schistosomiasis and with the nephrotic syndrome were studied. Of the seven patients' sera examined, all had markedly low complement C3 and near normal C4 levels. This indirectly suggests an active role of Salmonella endotoxin in the etiology of the nephrosis."}
{"id": "PMID:239607", "title": "[Delayed healings of the epithelium of the cornea due to soft lenssolutions].", "content": "Six different soft lens solution have been tested to investigate their effect on the healing process of a corneal erosion, experimentally scratched in rabbit-cornea. Healing delays have been observed in every cases; also by three medicaments which are used for \"dry\" eyes. The latter ones should never have  a conjunctival application. Theexplanation of those  healing delays is given by the concentration properties of HEMA-lenses for disinfectants. The admixtures of soft lens solutions like buffers and liquid polymerscause and additive effect on retardment of coeneal regeneration.", "contents": "[Delayed healings of the epithelium of the cornea due to soft lenssolutions]. Six different soft lens solution have been tested to investigate their effect on the healing process of a corneal erosion, experimentally scratched in rabbit-cornea. Healing delays have been observed in every cases; also by three medicaments which are used for \"dry\" eyes. The latter ones should never have  a conjunctival application. Theexplanation of those  healing delays is given by the concentration properties of HEMA-lenses for disinfectants. The admixtures of soft lens solutions like buffers and liquid polymerscause and additive effect on retardment of coeneal regeneration."}
{"id": "PMID:239608", "title": "A paradoxical action of minute doses of nondepolarizing muscle relaxants in anaesthetized man.", "content": "The administration of minute doses of all currently available nondepolarizing muscle relaxants result in an increase in contractile force of the skeletal muscles. This surprising finding has been obtained by means of mechanograms of the hand muscles after electrical stimulation of the ulnar nerve (100-200 volts, 0.3 msec, 0.2 Hz). Higher doses produce a decrease in contractile force and a paralysis of the skiltalmuscles. The paradoxical action of muscle relaxants can be explained by repetitive firing of the muscle action potential as has been demonstrated in the phrenic nerve-diaphragm preparation with tubocurarine and gallamine.", "contents": "A paradoxical action of minute doses of nondepolarizing muscle relaxants in anaesthetized man. The administration of minute doses of all currently available nondepolarizing muscle relaxants result in an increase in contractile force of the skeletal muscles. This surprising finding has been obtained by means of mechanograms of the hand muscles after electrical stimulation of the ulnar nerve (100-200 volts, 0.3 msec, 0.2 Hz). Higher doses produce a decrease in contractile force and a paralysis of the skiltalmuscles. The paradoxical action of muscle relaxants can be explained by repetitive firing of the muscle action potential as has been demonstrated in the phrenic nerve-diaphragm preparation with tubocurarine and gallamine."}
{"id": "PMID:239609", "title": "The effect of artifical ventilation and dehydrobenzperidol on the development of early changes in the respiratory system in dogs with Mendelson's syndrome.", "content": "The experiments were carried out to observe certain functional changes in the respiratory system which develop in the early stage of aspiration pneumonia and to study the possibility of influencing these changes by application of artificial ventilation (IPPB) and/or administration of dehydrobenzperidol. The experiments were carried out on 32 mongrel dogs divided into 4 groups. Experimental Mendelson's syndrome was produced by instilling, during anaesthesia, hydrochloric acid solution of pH 1.5 in a dose of 4 ml/kg into the tracheobronchial tree. Immediately after anaesthesia and then 10 times at intervals of one hour after HCl instillation the following determinations were done: mean blood pressure, CVP, haematocrit, PO2 and PCO2 in arterial and mixed venous blood, and minute artifical ventilation. The veno-arterial blood shunt in the lungs, alveolo-arterial difference of oxygen partial pressure and the effective compliance were also determined. The chemical damage to the lungs by acid caused condensation of blood and a fall in CVP. These changes were due to fluid escape from the vessels especially in the pulmonary vascular tree. Disturbances in pulmonary gas exchange were a result of deficient ventilation of lung areas damaged primarily by acid and suffering secondarily from developing disturbances in pulmonary blood flow. Dehydrobenzperidol in a dose of 1 mg/kg applied as the only treatment in Mendelson's syndrome had the same favourable effect on pulmonary changes as controlled IPPB. The combination of controlled artificial ventilation and intravenous dehydrobenzperidol decreased the disturbances in pulmonary gas exchange in Mendelson's syndrome. This was possible because both factors exert a benficial effect on ventilation and perfusion preventing the development of oedema and atelectasis.", "contents": "The effect of artifical ventilation and dehydrobenzperidol on the development of early changes in the respiratory system in dogs with Mendelson's syndrome. The experiments were carried out to observe certain functional changes in the respiratory system which develop in the early stage of aspiration pneumonia and to study the possibility of influencing these changes by application of artificial ventilation (IPPB) and/or administration of dehydrobenzperidol. The experiments were carried out on 32 mongrel dogs divided into 4 groups. Experimental Mendelson's syndrome was produced by instilling, during anaesthesia, hydrochloric acid solution of pH 1.5 in a dose of 4 ml/kg into the tracheobronchial tree. Immediately after anaesthesia and then 10 times at intervals of one hour after HCl instillation the following determinations were done: mean blood pressure, CVP, haematocrit, PO2 and PCO2 in arterial and mixed venous blood, and minute artifical ventilation. The veno-arterial blood shunt in the lungs, alveolo-arterial difference of oxygen partial pressure and the effective compliance were also determined. The chemical damage to the lungs by acid caused condensation of blood and a fall in CVP. These changes were due to fluid escape from the vessels especially in the pulmonary vascular tree. Disturbances in pulmonary gas exchange were a result of deficient ventilation of lung areas damaged primarily by acid and suffering secondarily from developing disturbances in pulmonary blood flow. Dehydrobenzperidol in a dose of 1 mg/kg applied as the only treatment in Mendelson's syndrome had the same favourable effect on pulmonary changes as controlled IPPB. The combination of controlled artificial ventilation and intravenous dehydrobenzperidol decreased the disturbances in pulmonary gas exchange in Mendelson's syndrome. This was possible because both factors exert a benficial effect on ventilation and perfusion preventing the development of oedema and atelectasis."}
{"id": "PMID:239610", "title": "Comparison of controlled respiration by the manual technique and with a respirator during general anaesthesia for abdominal operations.", "content": "These studies investigating the difference between controlled respiration performed by manual technique and controlled respiration applied by means of a respirator during general anaesthesia, and assessing the influence of these methods on the immediate post-operative condition of the patient were carried out on 75 patients during abdominal operations. Gasometric tests in arterial blood were performed before premedication, at intervals of 30 min from the beginning of operation, and 10 min. after the removal of the endotracheal tube. Controlled respiration with a respirator is a more favourable method of pulmonary ventilation during general anaesthesia given for a long-lasting surgical operation. The manual technique of controlled respiration leads to respiratory alkalosis. The best results were obtained using a respirator with inspiratory volume of 10 ml/kg and respiratory frequency 10/min., which ensured normocapnia. It was observed that oxygenation of arterial blood was reduced postoperatively in all patients but the value of PaO2 was the lowest in patients on manual controlled respiration. Disturbances in acid-base balance and oxygenation had an unfavourable effect and delayed the regaining of consciousness.", "contents": "Comparison of controlled respiration by the manual technique and with a respirator during general anaesthesia for abdominal operations. These studies investigating the difference between controlled respiration performed by manual technique and controlled respiration applied by means of a respirator during general anaesthesia, and assessing the influence of these methods on the immediate post-operative condition of the patient were carried out on 75 patients during abdominal operations. Gasometric tests in arterial blood were performed before premedication, at intervals of 30 min from the beginning of operation, and 10 min. after the removal of the endotracheal tube. Controlled respiration with a respirator is a more favourable method of pulmonary ventilation during general anaesthesia given for a long-lasting surgical operation. The manual technique of controlled respiration leads to respiratory alkalosis. The best results were obtained using a respirator with inspiratory volume of 10 ml/kg and respiratory frequency 10/min., which ensured normocapnia. It was observed that oxygenation of arterial blood was reduced postoperatively in all patients but the value of PaO2 was the lowest in patients on manual controlled respiration. Disturbances in acid-base balance and oxygenation had an unfavourable effect and delayed the regaining of consciousness."}
{"id": "PMID:239615", "title": "Influence of mare uterine tubal fluids on the metabolism of stallion sperm.", "content": "Three experiments were conducted on the metabolism of stallion sperm. In experiment 1, whole and washed sperm were incubated under aerobic and anaerobic enviroments and analyzed before and after controlled incubation for motility, pH, lactic acid, glucose, fructose, and O2 comsumption. In experiment 2, whole and washed sperm were incubated aerobically and anaerobically with and without uterine tubal fluids. Experiment 3 was the same as experiment 2, except added substrates of glucose and lactic acid were studied. The same examinations were made in experiments 2 and 3 as for experiment 1. Motility decreased significantly during incubation for all treatments, with the greatest decrease occurring for whole semen where only trace amounts of substrate (fructose) were present. Exogenous glucose plus uterine tubal fluid maintained sperm motility better than did added lactate. However, sperm respiration rates were highest when exogenous lactate was the only substrate in the incubation medium. The mean pH values for gel-free stallion semen at the start of controlled aerobic and anaerobic incubation were 7.08 and 7.34. Lactic acid accummulation for 1 hour increased from 0.05 mg to 0.09 mg/10(9) sperm when uterine tubal fluid was added to the incubation medium. Washed spermatozoa incubated in 0.03 M glucose plus uterine tubal fluid utilized less glucose than did sperm incubated in the glucose medium. These results, along with the increased oxygen utilization (ZO2) values produced by adding uterine tubal fluid to the incubation mediums, might indicate utilization of a uterine tubal substrate. Added uterine tubal fluid resulted in increased ZO2 values (expressed in mul of O2 utilized by 10(8) sperm in 1 hour at 37 C) for whole semen from 10.45 to 12.63. Washed spermatozoa also respired at a significantly greater rate than whole sperm. Respiration rates were greater for sperm incubated with 0.01 M lactic acid than for any other substrate or experiment.", "contents": "Influence of mare uterine tubal fluids on the metabolism of stallion sperm. Three experiments were conducted on the metabolism of stallion sperm. In experiment 1, whole and washed sperm were incubated under aerobic and anaerobic enviroments and analyzed before and after controlled incubation for motility, pH, lactic acid, glucose, fructose, and O2 comsumption. In experiment 2, whole and washed sperm were incubated aerobically and anaerobically with and without uterine tubal fluids. Experiment 3 was the same as experiment 2, except added substrates of glucose and lactic acid were studied. The same examinations were made in experiments 2 and 3 as for experiment 1. Motility decreased significantly during incubation for all treatments, with the greatest decrease occurring for whole semen where only trace amounts of substrate (fructose) were present. Exogenous glucose plus uterine tubal fluid maintained sperm motility better than did added lactate. However, sperm respiration rates were highest when exogenous lactate was the only substrate in the incubation medium. The mean pH values for gel-free stallion semen at the start of controlled aerobic and anaerobic incubation were 7.08 and 7.34. Lactic acid accummulation for 1 hour increased from 0.05 mg to 0.09 mg/10(9) sperm when uterine tubal fluid was added to the incubation medium. Washed spermatozoa incubated in 0.03 M glucose plus uterine tubal fluid utilized less glucose than did sperm incubated in the glucose medium. These results, along with the increased oxygen utilization (ZO2) values produced by adding uterine tubal fluid to the incubation mediums, might indicate utilization of a uterine tubal substrate. Added uterine tubal fluid resulted in increased ZO2 values (expressed in mul of O2 utilized by 10(8) sperm in 1 hour at 37 C) for whole semen from 10.45 to 12.63. Washed spermatozoa also respired at a significantly greater rate than whole sperm. Respiration rates were greater for sperm incubated with 0.01 M lactic acid than for any other substrate or experiment."}
{"id": "PMID:239618", "title": "[Alterations of renal function in pyelonephritis (author's transl)].", "content": "Renal function was investigated in a group of ten patients aged two months to eleven years, with chronic or recurrent urinary tract infection caused by different malformations of the urinary tract. The following tests were performed: endogenous creatinine clearance, maximal urinary concentrating ability, urinary acidification, maximal urinary diluting ability, free water clearance, index of fractional distal sodium delivery and index of distal tubular reabsorption of sodium. It is concluded that the follow-up of glomerular function by means of creatinine clearance and of tubular function by means of maximal concentrating ability consitute the most sensible way to detect renal functional impairment in children with chronic or recurrent pyelonephritis.", "contents": "[Alterations of renal function in pyelonephritis (author's transl)]. Renal function was investigated in a group of ten patients aged two months to eleven years, with chronic or recurrent urinary tract infection caused by different malformations of the urinary tract. The following tests were performed: endogenous creatinine clearance, maximal urinary concentrating ability, urinary acidification, maximal urinary diluting ability, free water clearance, index of fractional distal sodium delivery and index of distal tubular reabsorption of sodium. It is concluded that the follow-up of glomerular function by means of creatinine clearance and of tubular function by means of maximal concentrating ability consitute the most sensible way to detect renal functional impairment in children with chronic or recurrent pyelonephritis."}
{"id": "PMID:239621", "title": "Recurrent wound sinuses after cholecystectomy for salmonella paratyphi.", "content": "Several cases in which Salmonella, spread by the haematogenous route, produced localised inflammation have previously been described in the literature. The infecting of an operation wound through direct contamination by Salmonella has earlier been reported only once, in connection with appendectomy. The present case report describes a case in which recurrent sinuses infected by Salmonella were formed in the operative wound.", "contents": "Recurrent wound sinuses after cholecystectomy for salmonella paratyphi. Several cases in which Salmonella, spread by the haematogenous route, produced localised inflammation have previously been described in the literature. The infecting of an operation wound through direct contamination by Salmonella has earlier been reported only once, in connection with appendectomy. The present case report describes a case in which recurrent sinuses infected by Salmonella were formed in the operative wound."}
{"id": "PMID:239622", "title": "The effect of drug therapy without volume replacement in experimental traumatic shock. Part I. Phenoxybenzamine and dopamine.", "content": "The effect of phenoxybenzamine and dopamine on the respiratory and metabolic changes in experimental traumatic shock was examined in 45 rabbits. Phenoxybenzamine caused a more effective release of the peripheral vasoconstriction than dopamine. The effect of these drugs without similar restoration of blood volume was unfavourable. This should be borne in mind when the use of these drugs is meditated in clinical work.", "contents": "The effect of drug therapy without volume replacement in experimental traumatic shock. Part I. Phenoxybenzamine and dopamine. The effect of phenoxybenzamine and dopamine on the respiratory and metabolic changes in experimental traumatic shock was examined in 45 rabbits. Phenoxybenzamine caused a more effective release of the peripheral vasoconstriction than dopamine. The effect of these drugs without similar restoration of blood volume was unfavourable. This should be borne in mind when the use of these drugs is meditated in clinical work."}
{"id": "PMID:239623", "title": "The effect of drug therapy without volume restoration in experimental traumatic shock. Part II. Pethidine.", "content": "Different opinions seem to exist as to the use of analgesies in the treatment of trauma patients. For this reason we investigated experimentally the effect of pethidine in traumatic shock. Pethidine was administrated to eight of sixteen anaesthetized rabbits with lower limb injuries. The effect of pethidine was unfavourable. This was due to the effect of the drug on circulation and not on respiration.", "contents": "The effect of drug therapy without volume restoration in experimental traumatic shock. Part II. Pethidine. Different opinions seem to exist as to the use of analgesies in the treatment of trauma patients. For this reason we investigated experimentally the effect of pethidine in traumatic shock. Pethidine was administrated to eight of sixteen anaesthetized rabbits with lower limb injuries. The effect of pethidine was unfavourable. This was due to the effect of the drug on circulation and not on respiration."}
{"id": "PMID:239619", "title": "[Asparagine metabolism in mycobacteria. II. -- Asparagine hydrolysis and aspartohydroxamic acid formation and hydrolysis catalysed by M. fortuitum, M. phlei and BCG asparaginases (author's transl)].", "content": "Crude extracts of BCG, M. fortuitum and M. phlei, hydrolyse asparagine (I) and L-beta-asparthohydroxamic acid (III), and catalyse the synthesis of aspartohydroxamic acid from asparagine and hydroxylamine (II). The ratio between these enzymatic activities (I:II and I:III) presents a certain stability during the different steps of purification of these mycobacteria asparaginases. In particular, M. fortuitum asparaginase has been purified 90 to 130-fold, with recovery of approximately 10%. Only the fractions of supernatants which have an asparaginase activity catalyse the formation of aspartohydroxamate from asparagine and hydroxylamine. Some differences between the asparaginases of these strains are described. Particularaly, in comparison to reaction I, their abilities to catalyse reactions II and III vary noticeably from one asparaginase to an other. The asparaginase of BCG catalyses very slightly in the reactions II and III and is more specific of L-asparagine hydrolysis than are the asparaginases of M. fortuitum and of M. phlei. Furthermore, in the case of M. phlei, p-chloromercuribenzoate (pCMB) inhibits very stronly the reactions I and III and slightly reaction II, whereas conversely, for M. fortuitum, pCMB does not inhibit reactions I and III but strongly inhibits reaction II. In the case of BCG, these three reactions are not inhibited by pCMB. Moreover, the asparaginases from these strains are more or less sensitive to the ionic strength of the buffer used.", "contents": "[Asparagine metabolism in mycobacteria. II. -- Asparagine hydrolysis and aspartohydroxamic acid formation and hydrolysis catalysed by M. fortuitum, M. phlei and BCG asparaginases (author's transl)]. Crude extracts of BCG, M. fortuitum and M. phlei, hydrolyse asparagine (I) and L-beta-asparthohydroxamic acid (III), and catalyse the synthesis of aspartohydroxamic acid from asparagine and hydroxylamine (II). The ratio between these enzymatic activities (I:II and I:III) presents a certain stability during the different steps of purification of these mycobacteria asparaginases. In particular, M. fortuitum asparaginase has been purified 90 to 130-fold, with recovery of approximately 10%. Only the fractions of supernatants which have an asparaginase activity catalyse the formation of aspartohydroxamate from asparagine and hydroxylamine. Some differences between the asparaginases of these strains are described. Particularaly, in comparison to reaction I, their abilities to catalyse reactions II and III vary noticeably from one asparaginase to an other. The asparaginase of BCG catalyses very slightly in the reactions II and III and is more specific of L-asparagine hydrolysis than are the asparaginases of M. fortuitum and of M. phlei. Furthermore, in the case of M. phlei, p-chloromercuribenzoate (pCMB) inhibits very stronly the reactions I and III and slightly reaction II, whereas conversely, for M. fortuitum, pCMB does not inhibit reactions I and III but strongly inhibits reaction II. In the case of BCG, these three reactions are not inhibited by pCMB. Moreover, the asparaginases from these strains are more or less sensitive to the ionic strength of the buffer used."}
{"id": "PMID:239624", "title": "The effect of drug therapy without volume restoration in experimental traumatic shock. Part III. Glucocorticoid.", "content": "The effects of methylprednisolone in connexion with a standardized trauma was studied on 30 rabbits. The treatment with glucocorticoid accentuated the hemodilution due to the trauma. Intensified lactacidosis was also demonstrated.", "contents": "The effect of drug therapy without volume restoration in experimental traumatic shock. Part III. Glucocorticoid. The effects of methylprednisolone in connexion with a standardized trauma was studied on 30 rabbits. The treatment with glucocorticoid accentuated the hemodilution due to the trauma. Intensified lactacidosis was also demonstrated."}
{"id": "PMID:239620", "title": "[Remarks on ethanol oxidation by an \"Acetobacter xylinum\" microbial electrode (author's transl)].", "content": "A \"microbial electrode\" for ethanol assay has been designed using combination of an oxygen probe and cellulosic pellicle of Acetobacter xylinum. Assay is feasible with an ethanol concentration below 0.4 mM on a pH range of 2,5-7. The formation of acetic acid leds to a competitive inhibition of ethanol oxidation as observed with free cells. Pellicle stability at room temperature is good over a ten hours period. At 4 degrees C, film preservation is quite satisfactory over a ten days storage period. The author compares the ethanol oxidation kinetics observed, using both cellulosic pellicles and free cells of A. xylinum.", "contents": "[Remarks on ethanol oxidation by an \"Acetobacter xylinum\" microbial electrode (author's transl)]. A \"microbial electrode\" for ethanol assay has been designed using combination of an oxygen probe and cellulosic pellicle of Acetobacter xylinum. Assay is feasible with an ethanol concentration below 0.4 mM on a pH range of 2,5-7. The formation of acetic acid leds to a competitive inhibition of ethanol oxidation as observed with free cells. Pellicle stability at room temperature is good over a ten hours period. At 4 degrees C, film preservation is quite satisfactory over a ten days storage period. The author compares the ethanol oxidation kinetics observed, using both cellulosic pellicles and free cells of A. xylinum."}
{"id": "PMID:239625", "title": "An inducible beta-lactamase in a strain of Escherichia coli.", "content": "The production of beta-lactamase (penicillin/cephalosporin beta-lactam amidohydrolase, E.C.3.5.2.6) was found to be inducible in a clinically isolated strain of Escherichia coli. This is the first report of an inducible beta-lactamase in E. coli. The optimal concentration of inducer was 400 mug/ml of ml of benzylpenicillin, or 800 mug/ml of 6-aminopenicillanic acid. About fiftyfold induction was achieved. Maximum induction took ninety minutes from the time of adding the inducer. Induction was abolished by the presence of chloramphenicol(10 mug/ml). The enzyme has a molecular wieght of 23,000, and is inhibited by rho-chloromercuribenzoate and by iodine. It is active against a wide range of substrates, including cephaloridine and cloxacillin.", "contents": "An inducible beta-lactamase in a strain of Escherichia coli. The production of beta-lactamase (penicillin/cephalosporin beta-lactam amidohydrolase, E.C.3.5.2.6) was found to be inducible in a clinically isolated strain of Escherichia coli. This is the first report of an inducible beta-lactamase in E. coli. The optimal concentration of inducer was 400 mug/ml of ml of benzylpenicillin, or 800 mug/ml of 6-aminopenicillanic acid. About fiftyfold induction was achieved. Maximum induction took ninety minutes from the time of adding the inducer. Induction was abolished by the presence of chloramphenicol(10 mug/ml). The enzyme has a molecular wieght of 23,000, and is inhibited by rho-chloromercuribenzoate and by iodine. It is active against a wide range of substrates, including cephaloridine and cloxacillin."}
{"id": "PMID:239626", "title": "A novel inducible formaldehyde dehyrogenase of Pseudomonas sp. (RJ1).", "content": "A novel, pyridine-nucleotide-independent, inducible formaldehyde dehydrogenase acitivity was detected in cells of Pseudomonas sp. (RJ1) propagated on methylamine and oxalated. The pH optimum of the dehydrogenase was 7.0. Dichlorophenol-indophenol or potassium ferricyanide served as an electron acceptor. The rate of reduction of these electron acceptors was shown to be stimulated by phenazine methosulfate. The dehydrogenase was inhibited by parahydroxymercuric benzoate and iodoacetamide. This inhibition suggests that the enzyme contains sulfhydryl groups. The stoichiometry of the reaction in terms of oxygen uptake to formate formation was 0.5, which agrees with the theoretical value.", "contents": "A novel inducible formaldehyde dehyrogenase of Pseudomonas sp. (RJ1). A novel, pyridine-nucleotide-independent, inducible formaldehyde dehydrogenase acitivity was detected in cells of Pseudomonas sp. (RJ1) propagated on methylamine and oxalated. The pH optimum of the dehydrogenase was 7.0. Dichlorophenol-indophenol or potassium ferricyanide served as an electron acceptor. The rate of reduction of these electron acceptors was shown to be stimulated by phenazine methosulfate. The dehydrogenase was inhibited by parahydroxymercuric benzoate and iodoacetamide. This inhibition suggests that the enzyme contains sulfhydryl groups. The stoichiometry of the reaction in terms of oxygen uptake to formate formation was 0.5, which agrees with the theoretical value."}
{"id": "PMID:239627", "title": "The occurrence of killer character in yeasts of various genera.", "content": "Species of 7 of the 28 yeast genera in the National Collection of Yeast Cultures exhibited killing activity against Saccharomyces cerevisiae. The highest incidence of killer yeasts was found in the genus Hansenula (12 of the 29 strains examined). Saccharomyces, the best represented genus in the Collection, showed a low incidence of killer activity and many of the killer strains are hybrids with a common S. cerevisiae parent. The activities of culture filtrates of the 59 killer yeast isolated responded differently to pH and four types of response were recognised.", "contents": "The occurrence of killer character in yeasts of various genera. Species of 7 of the 28 yeast genera in the National Collection of Yeast Cultures exhibited killing activity against Saccharomyces cerevisiae. The highest incidence of killer yeasts was found in the genus Hansenula (12 of the 29 strains examined). Saccharomyces, the best represented genus in the Collection, showed a low incidence of killer activity and many of the killer strains are hybrids with a common S. cerevisiae parent. The activities of culture filtrates of the 59 killer yeast isolated responded differently to pH and four types of response were recognised."}
{"id": "PMID:239628", "title": "Properties of D-xylose isomerase from Streptomyces albus.", "content": "A partially purified D-xylose isomerase has been isolated from cells of Streptomyces albus NRRL 5778 and some of its properties have been determined. D-Glucose, D-xylose, D-ribose, L-arabinose, and L-rhamnose served as substrates for the enzyme with respective Km values of 86, 93, 350, 153, and 312 mM and Vmax values measuring 1.23, 2.9, 2.63, 0.153, and 0.048 mumol min per mg of protein. The hexose D-allose was also isomerized. The enzyme was strongly activated by 1.0 mM Mg2+ but only partially activated by 1.0 mM Co2+. The respective Km values for Mg2+ and Co2+ were 0.3 and 0.003 mM. Mg2+ and Co2+ appear to have separate binding sites on the isomerase. These cations also protect the enzyme from thermal denaturation and from D-sorbitol inhibition. The optimum temperature for ketose formation was 70 to 80 C at pH values ranging from 7 to 9. D-Sorbitol acts as a competitive inhibitor with a Ki of 5.5 mM against D-glucose, D-xylose, and D-ribose. Induction experiments, Mg2+ activation, and D-sorbitol inhibition indicated that a single enzyme (D-xylose isomerase) was responsible for the isomerization of the pentoses, methyl pentose, and glucose.", "contents": "Properties of D-xylose isomerase from Streptomyces albus. A partially purified D-xylose isomerase has been isolated from cells of Streptomyces albus NRRL 5778 and some of its properties have been determined. D-Glucose, D-xylose, D-ribose, L-arabinose, and L-rhamnose served as substrates for the enzyme with respective Km values of 86, 93, 350, 153, and 312 mM and Vmax values measuring 1.23, 2.9, 2.63, 0.153, and 0.048 mumol min per mg of protein. The hexose D-allose was also isomerized. The enzyme was strongly activated by 1.0 mM Mg2+ but only partially activated by 1.0 mM Co2+. The respective Km values for Mg2+ and Co2+ were 0.3 and 0.003 mM. Mg2+ and Co2+ appear to have separate binding sites on the isomerase. These cations also protect the enzyme from thermal denaturation and from D-sorbitol inhibition. The optimum temperature for ketose formation was 70 to 80 C at pH values ranging from 7 to 9. D-Sorbitol acts as a competitive inhibitor with a Ki of 5.5 mM against D-glucose, D-xylose, and D-ribose. Induction experiments, Mg2+ activation, and D-sorbitol inhibition indicated that a single enzyme (D-xylose isomerase) was responsible for the isomerization of the pentoses, methyl pentose, and glucose."}
{"id": "PMID:239629", "title": "Death of Staphylococcus aureus in liquid whole egg near pH 8.", "content": "Incubating and shaking Staphylococcus aureus in liquid whole egg causes a decline in viability. During the period of agitation, the natural pH of the egg rises from about 7.2 to between 8.0 and 8.2 as a result of a loss of carbon dioxide. However, if the pH of the egg is prevented from rising, either by not shaking or by addition of a buffer, S. aureus will grow. The cause of death is traced to the presence of lysozyme of egg white. Interestingly, the action of lysozyme is not attributable to its bacterial lytic property but, instead, to the basicity of the lysozyme molecule. This conclusion is supported by the fact that the lytic property of lysozyme is known to have its optimal activity near neutrality and by the finding that protamine sulfate, a nonenzymatic basic polypeptide, also caused death of S. aureus at pH 8.0 but not at 7.0. It was postulated that the rise in pH renders the bacterial cells more negatively charged, so that in the presence of positively charged molecules like lysozyme or protamine sulfate a complex is formed, agglutinating the cells.", "contents": "Death of Staphylococcus aureus in liquid whole egg near pH 8. Incubating and shaking Staphylococcus aureus in liquid whole egg causes a decline in viability. During the period of agitation, the natural pH of the egg rises from about 7.2 to between 8.0 and 8.2 as a result of a loss of carbon dioxide. However, if the pH of the egg is prevented from rising, either by not shaking or by addition of a buffer, S. aureus will grow. The cause of death is traced to the presence of lysozyme of egg white. Interestingly, the action of lysozyme is not attributable to its bacterial lytic property but, instead, to the basicity of the lysozyme molecule. This conclusion is supported by the fact that the lytic property of lysozyme is known to have its optimal activity near neutrality and by the finding that protamine sulfate, a nonenzymatic basic polypeptide, also caused death of S. aureus at pH 8.0 but not at 7.0. It was postulated that the rise in pH renders the bacterial cells more negatively charged, so that in the presence of positively charged molecules like lysozyme or protamine sulfate a complex is formed, agglutinating the cells."}
{"id": "PMID:239630", "title": "Degradation of ethylenediaminetetraacetic acid by mictobial populations from an aerated lagoon.", "content": "The ferric chelate of ethylenediaminetetraacetic acid (EDTA) was biologically degraded by a mixed population of microorganisms present in an aerated lagoon receiving this chemical in its feed. As determined radiorespirometrically, 28% of the acetate-2-C and 30% of the ethylene position of the ammonium ferric chelate of [14C]EDTA was recovered as 14CO2 after 5 days. In a separate experiment using gas liquid chromatography and the sodium ferric chelate, as much as 89% disappearance of EDTA (0.1% wt/vol) was observed during a similar time period. Optimum 14CO2 evolution was observed at a pH value between 7 and 8 and at room temperature. Degradation of NH4Fe-[2-14C]EDTA was stimulated by the addition of either unlabeled NaFe-EDTA, nitrilotriacetic acid or ethylenediamine, and inhibited by the addition of a variety of different sugars and amino acids. Consistent with the biological nature of this degradation, little or no 14CO2 evolution was observed after heat treatment of the microorganisms at 100 C for 10 min, or after the addition of antibiotics to the incubation mixtures. Gas-liquid chromatography and mass spectral analyses were performed to demonstrate EDTA disappearance and to identify possible intermediates of EDTA degradation.", "contents": "Degradation of ethylenediaminetetraacetic acid by mictobial populations from an aerated lagoon. The ferric chelate of ethylenediaminetetraacetic acid (EDTA) was biologically degraded by a mixed population of microorganisms present in an aerated lagoon receiving this chemical in its feed. As determined radiorespirometrically, 28% of the acetate-2-C and 30% of the ethylene position of the ammonium ferric chelate of [14C]EDTA was recovered as 14CO2 after 5 days. In a separate experiment using gas liquid chromatography and the sodium ferric chelate, as much as 89% disappearance of EDTA (0.1% wt/vol) was observed during a similar time period. Optimum 14CO2 evolution was observed at a pH value between 7 and 8 and at room temperature. Degradation of NH4Fe-[2-14C]EDTA was stimulated by the addition of either unlabeled NaFe-EDTA, nitrilotriacetic acid or ethylenediamine, and inhibited by the addition of a variety of different sugars and amino acids. Consistent with the biological nature of this degradation, little or no 14CO2 evolution was observed after heat treatment of the microorganisms at 100 C for 10 min, or after the addition of antibiotics to the incubation mixtures. Gas-liquid chromatography and mass spectral analyses were performed to demonstrate EDTA disappearance and to identify possible intermediates of EDTA degradation."}
{"id": "PMID:239631", "title": "Method for detecting small numbers of Vibrio cholerae in very polluted substrates.", "content": "A method is presented for the indirect detection of Vibrio cholerae by the multiplication of two specific bacteriophages: phiH74/64 for El-Tor vibrios, and phage group IV (Mukerjee) for classical vibrios. The product to be examined is seeded in alkaline tryptone water for enrichment, as in the classical method, and is then incubated for 6 h at 37 C. Thereafter, a loopful is transferred to each of two nutrient broth (pH 9) tubes. One of these receives a drop of phage phiH74/64; the other receives a drop of phage group IV. The stock phages are diluted so as to contain about 3,800 plaque-forming units in one drop; this is the maximum amount which, when added to 10 ml of broth, will not be detected in a loopful of 1 mm diameter. The tubes containing phage phiH74/64 are incubated at 42 C; those with phage group IV are incubated at 37 C. After 18 h the cultures are killed by agitation with chloroform, and a 1-mm loopful is deposited on a layer seeded with the detector strains: Makassar 757 for El-Tor phage and V. cholerae 154 for classical cholera phage. After 4 to 5 h at 37 C, lysis appears on the spot areas if there has been phage multiplication in the respective broth tubes. With experimentally contaminated sewage water, vegetables, or stools, 1 to 10 cholera vibrios were detected in every sample. In rare cases, false-positive results were obtained by multiplication of the phage on non-cholera vibrios.", "contents": "Method for detecting small numbers of Vibrio cholerae in very polluted substrates. A method is presented for the indirect detection of Vibrio cholerae by the multiplication of two specific bacteriophages: phiH74/64 for El-Tor vibrios, and phage group IV (Mukerjee) for classical vibrios. The product to be examined is seeded in alkaline tryptone water for enrichment, as in the classical method, and is then incubated for 6 h at 37 C. Thereafter, a loopful is transferred to each of two nutrient broth (pH 9) tubes. One of these receives a drop of phage phiH74/64; the other receives a drop of phage group IV. The stock phages are diluted so as to contain about 3,800 plaque-forming units in one drop; this is the maximum amount which, when added to 10 ml of broth, will not be detected in a loopful of 1 mm diameter. The tubes containing phage phiH74/64 are incubated at 42 C; those with phage group IV are incubated at 37 C. After 18 h the cultures are killed by agitation with chloroform, and a 1-mm loopful is deposited on a layer seeded with the detector strains: Makassar 757 for El-Tor phage and V. cholerae 154 for classical cholera phage. After 4 to 5 h at 37 C, lysis appears on the spot areas if there has been phage multiplication in the respective broth tubes. With experimentally contaminated sewage water, vegetables, or stools, 1 to 10 cholera vibrios were detected in every sample. In rare cases, false-positive results were obtained by multiplication of the phage on non-cholera vibrios."}
{"id": "PMID:239632", "title": "Influence of colloidal iron on the respiration of a species of the genus Acinetobacter.", "content": "Washed suspensions of Acinetobacter sp. isolated from water caused the precipitation of iron from a suspension of colloidal ferric iron at pH 6.0 and 7.6. Iron-encrusted cells of the bacterium formed large aggregates. The amount of iron removed from the colloidal preparation in the form of aggregates was from 21 to 52% at pH 7.6 and 49% an pH 6.0 by the bacterial cells. Endogenous respiration rates of the iron-encrusted cells were from 32 to 72% lower than the rates for unencrusted cells. Respiration rates, measured polarographically in the presence of glucose, were also greatly reduced by the coating of iron on the cells.", "contents": "Influence of colloidal iron on the respiration of a species of the genus Acinetobacter. Washed suspensions of Acinetobacter sp. isolated from water caused the precipitation of iron from a suspension of colloidal ferric iron at pH 6.0 and 7.6. Iron-encrusted cells of the bacterium formed large aggregates. The amount of iron removed from the colloidal preparation in the form of aggregates was from 21 to 52% at pH 7.6 and 49% an pH 6.0 by the bacterial cells. Endogenous respiration rates of the iron-encrusted cells were from 32 to 72% lower than the rates for unencrusted cells. Respiration rates, measured polarographically in the presence of glucose, were also greatly reduced by the coating of iron on the cells."}
{"id": "PMID:239643", "title": "Epidermal nicotinamide adenine dinucleotides in psoriasis and neurodermatitis (lichen simplex hypertrophicus).", "content": "Epidermal nicotinamide adenine dinucleotides were measured in subcorneal and basal epidermal layers in patients with psoriasis and neurodermatitis and in healthy controls. Lowry's microtechniques utilizing enzymatic cycling were used. The total NAD content in these groups was except for the involved psoriatic skin about 1.1 mmoles/kg dry weight. Between 40 and 50% of this content consisted of the reduced form. In the involved psoriatic skin the total NAD content was increased to 1.5 mmoles/kg, this increase being mainly due to a rise in NAD+. There was no difference in NAD content between epidermal layers in the various groups studied. The total NADP content was near 0.15 mmoles/kg in healthy controls and in patients with neurodermatitis. The subcorneal layers contained 10% more of the dinucleotide than the basal layers, but in the two layers the reduced form amounted to about 80% of the total. In both non-involved and involved skin of the psoriatic patients the total NADP content was significantly increased above the control level, by up to 20% in the former and up to 65% in the latter. In the two layers studied the NADP+ content was increased by about 75% in both non-involved and involved areas. In contrast, the NADPH content rose only in the basal layers of the lesion, by 55%. The increased levels of NADP+ and NADPH found in psoriasis might suggest an accelerated or differently conducted NADPH dependent biosynthesis in this disease.", "contents": "Epidermal nicotinamide adenine dinucleotides in psoriasis and neurodermatitis (lichen simplex hypertrophicus). Epidermal nicotinamide adenine dinucleotides were measured in subcorneal and basal epidermal layers in patients with psoriasis and neurodermatitis and in healthy controls. Lowry's microtechniques utilizing enzymatic cycling were used. The total NAD content in these groups was except for the involved psoriatic skin about 1.1 mmoles/kg dry weight. Between 40 and 50% of this content consisted of the reduced form. In the involved psoriatic skin the total NAD content was increased to 1.5 mmoles/kg, this increase being mainly due to a rise in NAD+. There was no difference in NAD content between epidermal layers in the various groups studied. The total NADP content was near 0.15 mmoles/kg in healthy controls and in patients with neurodermatitis. The subcorneal layers contained 10% more of the dinucleotide than the basal layers, but in the two layers the reduced form amounted to about 80% of the total. In both non-involved and involved skin of the psoriatic patients the total NADP content was significantly increased above the control level, by up to 20% in the former and up to 65% in the latter. In the two layers studied the NADP+ content was increased by about 75% in both non-involved and involved areas. In contrast, the NADPH content rose only in the basal layers of the lesion, by 55%. The increased levels of NADP+ and NADPH found in psoriasis might suggest an accelerated or differently conducted NADPH dependent biosynthesis in this disease."}
{"id": "PMID:239644", "title": "Epidermal nicotinamide adenine dinucleotides in psoriasis during treatment with dithranol.", "content": "Epidermal nicotinamide adenine dinucleotides were measured in subcorneal and basal epidermal layers in patients with psoriasis and in healthy controls during a 2-week period in which they were treated once a day with 0.15% dithranol in white petrolatum. Lowry's microtechniques utilizing enzymatic cycling were used. In the controls the total NAD contents decreased 25% during the treatment period. The total NADP content did not change, nor did the proportions of NADH and NADPH. In the psoriatic patients effects of the treatment were seen only in the epidermis of the lesions. Both the total NAD and NADP displayed an initial increase on the second day, followed by a steady decrease to the levels found in the non-involved skin. During the first week of treatment parakeratosis was still evident in the lesions. In spite of variation in the total NAD contents during this period, a significant reduction of the percentage of NADH was found. Concomitant with the appearance of an orthokeratotic horny layer, both NAD+ and NADH returned to normal. The percentage contribution of NADPH did not change during these events.", "contents": "Epidermal nicotinamide adenine dinucleotides in psoriasis during treatment with dithranol. Epidermal nicotinamide adenine dinucleotides were measured in subcorneal and basal epidermal layers in patients with psoriasis and in healthy controls during a 2-week period in which they were treated once a day with 0.15% dithranol in white petrolatum. Lowry's microtechniques utilizing enzymatic cycling were used. In the controls the total NAD contents decreased 25% during the treatment period. The total NADP content did not change, nor did the proportions of NADH and NADPH. In the psoriatic patients effects of the treatment were seen only in the epidermis of the lesions. Both the total NAD and NADP displayed an initial increase on the second day, followed by a steady decrease to the levels found in the non-involved skin. During the first week of treatment parakeratosis was still evident in the lesions. In spite of variation in the total NAD contents during this period, a significant reduction of the percentage of NADH was found. Concomitant with the appearance of an orthokeratotic horny layer, both NAD+ and NADH returned to normal. The percentage contribution of NADPH did not change during these events."}
{"id": "PMID:239645", "title": "Malaria studies in vitro. IV: Chloroquine resistance and the intracellular pH of erythrocytes parasitised with Plasmodium berghei.", "content": "The erythrocytic stages of strains of plasmodia sensitive to chloroquine (CQ) concentrate some three to six times more drug than CQ-resistant strains. A simple, but so far untested hypothesis is that the intracellular pH of drug resistant strains is higher than that for sensitive strains. This would result in a reduced accumulation of any weakly basic drug molecule (e.g. CQ) which is capable of passive diffusion through the cellular membran. The mean intracellular pH of erythrocytes parasitised with either CQ-sensitive or CQ-resistant strains of P. berghei was determined, therefore, from the distribution of 14C-5, 5-dimethyloxazolidine-2,4-dione between intra- and extracellular aqueous phases. The results obtained showed that over the range 6-8--7-2 the intracellular pH is governed directly by the extracellular pH and that the intracellular pH of CQ-sensitive parasites is slightly above that for resistant ones, neither being greatly different from that for uninfected erythrocytes. There was no evidence, therefore, to support, the suggested hypothesis. Elimination of this possibility adds weight to the opinion that changes in drug sensitivity of these plasmodia are the result of changes in the properties of drug-binding sites.", "contents": "Malaria studies in vitro. IV: Chloroquine resistance and the intracellular pH of erythrocytes parasitised with Plasmodium berghei. The erythrocytic stages of strains of plasmodia sensitive to chloroquine (CQ) concentrate some three to six times more drug than CQ-resistant strains. A simple, but so far untested hypothesis is that the intracellular pH of drug resistant strains is higher than that for sensitive strains. This would result in a reduced accumulation of any weakly basic drug molecule (e.g. CQ) which is capable of passive diffusion through the cellular membran. The mean intracellular pH of erythrocytes parasitised with either CQ-sensitive or CQ-resistant strains of P. berghei was determined, therefore, from the distribution of 14C-5, 5-dimethyloxazolidine-2,4-dione between intra- and extracellular aqueous phases. The results obtained showed that over the range 6-8--7-2 the intracellular pH is governed directly by the extracellular pH and that the intracellular pH of CQ-sensitive parasites is slightly above that for resistant ones, neither being greatly different from that for uninfected erythrocytes. There was no evidence, therefore, to support, the suggested hypothesis. Elimination of this possibility adds weight to the opinion that changes in drug sensitivity of these plasmodia are the result of changes in the properties of drug-binding sites."}
{"id": "PMID:239646", "title": "[Concomitant variations in the weight of adrenals and uremia during kidney provocation by high doses of glafenine].", "content": "High doses of glafenine given orally to rats induced renal tubular changes and simultaneously raised not only blood urea concentrations but also adrenal volume and weight. These modifications were transient and dose-dependent. Blood urea and adrenal weight returned to normal at the same time. Treated rats showed no alteration in serum K+, Na+, Cl-, uric acid, glucose and cholesterol and only a slight decrease in serum transaminase levels. An indirect relationship between renal lesions and adrenals hypertrophy induced by flafenine may exist.", "contents": "[Concomitant variations in the weight of adrenals and uremia during kidney provocation by high doses of glafenine]. High doses of glafenine given orally to rats induced renal tubular changes and simultaneously raised not only blood urea concentrations but also adrenal volume and weight. These modifications were transient and dose-dependent. Blood urea and adrenal weight returned to normal at the same time. Treated rats showed no alteration in serum K+, Na+, Cl-, uric acid, glucose and cholesterol and only a slight decrease in serum transaminase levels. An indirect relationship between renal lesions and adrenals hypertrophy induced by flafenine may exist."}
{"id": "PMID:239647", "title": "Sympathetic component of the pressor response to angiotensin II in the pithed rat after pretreatment with disulfiram.", "content": "Pressor responses to angiotensin II in the pithed rat were unaffected or slightly increased by procedures such as reserpine pretreatment, alpha and beta adrenoceptor blocking agents or bethanidine which inhibit the sympathetic system. Disulfiram-induced inhibition of angiotensin II pressor responses was unaffected by pretreatment with either alpha-adrenoceptor blockers or bethanidine. Pretreatment with disulfiram prevented infusions of angiotensin II from increasing the responses to spinal sympathetic outflow stimulation. After inhibition of pressor responses to angiotensin II by disulfiram the responses were restored by infusions of noradrenaline, or alpha-methyldopa. The restored responses, unlike control responses, were inhibited by phentolamine. The results suggest that angiotensin II facilitates neuronal release of noradrenaline and that this effect is revealed most clearly when post-synaptic angiotensin II receptors are blocked.", "contents": "Sympathetic component of the pressor response to angiotensin II in the pithed rat after pretreatment with disulfiram. Pressor responses to angiotensin II in the pithed rat were unaffected or slightly increased by procedures such as reserpine pretreatment, alpha and beta adrenoceptor blocking agents or bethanidine which inhibit the sympathetic system. Disulfiram-induced inhibition of angiotensin II pressor responses was unaffected by pretreatment with either alpha-adrenoceptor blockers or bethanidine. Pretreatment with disulfiram prevented infusions of angiotensin II from increasing the responses to spinal sympathetic outflow stimulation. After inhibition of pressor responses to angiotensin II by disulfiram the responses were restored by infusions of noradrenaline, or alpha-methyldopa. The restored responses, unlike control responses, were inhibited by phentolamine. The results suggest that angiotensin II facilitates neuronal release of noradrenaline and that this effect is revealed most clearly when post-synaptic angiotensin II receptors are blocked."}
{"id": "PMID:239648", "title": "Biologically active substances in oak gall extracts. Part 1: Isolation and chemical identification of a substance exerting antihistamine-like activity (KC-18).", "content": "The previously reported antihistamine-like activity of partially purified oak gall extracts has been confirmed. Isolation of the active principle was achieved through the use of organic solvent extractions and column chromatographic (Sephadex LH-20 and silica gel) procedures. Preliminary investigation on the structure of this chemically pure substance using mass spectrometry, thin layer chromatography, base hydrolysis and electrophoresis indicated that it is most probably an ester of piperonylic acid. KC-18, given intraperitoneally in doses of 4 mg/kg to guinea pigs 5 hours prior to an exposure to a 0.15 per cent histamine aerosol, significantly reduced the bronchoconstrictor effect of histamine.", "contents": "Biologically active substances in oak gall extracts. Part 1: Isolation and chemical identification of a substance exerting antihistamine-like activity (KC-18). The previously reported antihistamine-like activity of partially purified oak gall extracts has been confirmed. Isolation of the active principle was achieved through the use of organic solvent extractions and column chromatographic (Sephadex LH-20 and silica gel) procedures. Preliminary investigation on the structure of this chemically pure substance using mass spectrometry, thin layer chromatography, base hydrolysis and electrophoresis indicated that it is most probably an ester of piperonylic acid. KC-18, given intraperitoneally in doses of 4 mg/kg to guinea pigs 5 hours prior to an exposure to a 0.15 per cent histamine aerosol, significantly reduced the bronchoconstrictor effect of histamine."}
{"id": "PMID:239649", "title": "Biologically active substances in oak gall extracts. Part 11. The antihistamine-like activity of a substance (KC-18) isolated from oak gall extracts.", "content": "The effects of the newly isolated antihistamine (KC-18) from the Hungarian oak gall extracts on some actions of histamine have been investigated. Intraperitoneally administered KC-18 into guinea pigs and cats in doses of 2.5-16 mg/kg exerted a significant dose-related inhibition of histamine-induced bronchoconstriction, increase in capillary permeability and hypotension. In guinea pigs, actively sensitized with ovalbumin, 4 mg/kg KC-18 administered intraperitoneally prevented the development of anaphylactic shock following antigenic challenge. Histamine-induced gastric acid secretion in the rat was also dose-relatedly reduced by the intravenous administraton of 72 and 120 mg/kg KC-18. However, KC-18 in doses up to 100 mug/ml did not modify the histamine-induced contraction of the isolated guinea pig ileum.", "contents": "Biologically active substances in oak gall extracts. Part 11. The antihistamine-like activity of a substance (KC-18) isolated from oak gall extracts. The effects of the newly isolated antihistamine (KC-18) from the Hungarian oak gall extracts on some actions of histamine have been investigated. Intraperitoneally administered KC-18 into guinea pigs and cats in doses of 2.5-16 mg/kg exerted a significant dose-related inhibition of histamine-induced bronchoconstriction, increase in capillary permeability and hypotension. In guinea pigs, actively sensitized with ovalbumin, 4 mg/kg KC-18 administered intraperitoneally prevented the development of anaphylactic shock following antigenic challenge. Histamine-induced gastric acid secretion in the rat was also dose-relatedly reduced by the intravenous administraton of 72 and 120 mg/kg KC-18. However, KC-18 in doses up to 100 mug/ml did not modify the histamine-induced contraction of the isolated guinea pig ileum."}
{"id": "PMID:239650", "title": "Effects of drugs and sympathetic nerve stimuation  on retrograde coronary blood flow in dogs with experimental coronary occlusion.", "content": "Effects of nitroglycerin, dipyridamole, adenosine, reactive hyperemia, propranolol, norepinephrine and sympathetic nerve stimulation on retrograde coronary blood flow were investigated in dogs with experimental coronary occlusion. The retrograde blood flow (RF), pressure and conductance of the occluded left anterior descending coronary artery were measured and compared with the flow (CF), pressure and conductance of the non-occluded circumflex artery. The RF increased during sympathetic nerve stimulation and after the administration of nitroglycerin and norepinephrine, while it decreased during reactive hyperemia and following injection of dipyridamole, adenosine and propranolol. The RF/CF ratio was increased by nitroglycerin and propranolol, whereas it was lowered by dipyridamole and adenosine. The results suggest that nitroglycerin and propranolol may produce a redistribution of myocardial blood flow and that the collateral vessels are little influenced by sympathetic nerve stimulation.", "contents": "Effects of drugs and sympathetic nerve stimuation  on retrograde coronary blood flow in dogs with experimental coronary occlusion. Effects of nitroglycerin, dipyridamole, adenosine, reactive hyperemia, propranolol, norepinephrine and sympathetic nerve stimulation on retrograde coronary blood flow were investigated in dogs with experimental coronary occlusion. The retrograde blood flow (RF), pressure and conductance of the occluded left anterior descending coronary artery were measured and compared with the flow (CF), pressure and conductance of the non-occluded circumflex artery. The RF increased during sympathetic nerve stimulation and after the administration of nitroglycerin and norepinephrine, while it decreased during reactive hyperemia and following injection of dipyridamole, adenosine and propranolol. The RF/CF ratio was increased by nitroglycerin and propranolol, whereas it was lowered by dipyridamole and adenosine. The results suggest that nitroglycerin and propranolol may produce a redistribution of myocardial blood flow and that the collateral vessels are little influenced by sympathetic nerve stimulation."}
{"id": "PMID:239651", "title": "Antihistaminic action of (--)-trans-delta 9-tetrahydrocannabinol.", "content": "THC has an antagonistic effect against histamine on the isolated perfused guinea-pig lung and rabbit kidney. This antagonism seems to be a competitive one at the concentrations used and interacts with histamine at H1-receptors. THC also antagonizes the effect of acetylcholine, PGE2, angiotensis II and histamine in the isolated continuously superfused guinea-pig ileum by a non-competitive manner. The antagonism between THC and histamine on the isolated superfused rabbit aortic strips was found to be highly specific, since 100% relaxation was obtained when the muscle contracted by histamine but not by the equipotent doses of angiotensin II and noradrenaline. THC also causes a significant increase in survival time of guinea-pigs when the animals were exposed to histamine aerosol. These results indicate a specific antagonism of THC against histamine in the preparations used in this investigation.", "contents": "Antihistaminic action of (--)-trans-delta 9-tetrahydrocannabinol. THC has an antagonistic effect against histamine on the isolated perfused guinea-pig lung and rabbit kidney. This antagonism seems to be a competitive one at the concentrations used and interacts with histamine at H1-receptors. THC also antagonizes the effect of acetylcholine, PGE2, angiotensis II and histamine in the isolated continuously superfused guinea-pig ileum by a non-competitive manner. The antagonism between THC and histamine on the isolated superfused rabbit aortic strips was found to be highly specific, since 100% relaxation was obtained when the muscle contracted by histamine but not by the equipotent doses of angiotensin II and noradrenaline. THC also causes a significant increase in survival time of guinea-pigs when the animals were exposed to histamine aerosol. These results indicate a specific antagonism of THC against histamine in the preparations used in this investigation."}
{"id": "PMID:239652", "title": "[Peptic ulcer and insular carcinoma of the pancreas with hepatic metastasis (Zollinger-Ellison syndrome)].", "content": "A Zollinger-Ellison syndrome case is reported. During arteriography and surgical treatment islet cell carcinoma of the pancreas with metastasis to the liver was found. After surgery, patient has presented several periods of hypoglicemia. Hence it was speculated that this type of neoplasm might have double endocrine function.", "contents": "[Peptic ulcer and insular carcinoma of the pancreas with hepatic metastasis (Zollinger-Ellison syndrome)]. A Zollinger-Ellison syndrome case is reported. During arteriography and surgical treatment islet cell carcinoma of the pancreas with metastasis to the liver was found. After surgery, patient has presented several periods of hypoglicemia. Hence it was speculated that this type of neoplasm might have double endocrine function."}
{"id": "PMID:239653", "title": "Utilization of methanol by rhodospirillaceae.", "content": "Enrichment culture of organisms growing anaerobically in the light in methanol-bicarbonate medium resulted in isolation of strains of Rhodopseudomonas gelatinosa and Rhodopseudomonas acidophila. The pH optimum for growth on methanol for all strains tested was approximately one unit higher than for growth on carbon sources containing more than one carbon atom. At the appropriate pH, 17 strains of Rhodospirillaceae out of 39 in a culture collection grew anaerobically in the light on methanol-bicarbonate. Rhodopseudomonas acidophia strain 10050 showed the most abundant growth and was studied in more detail. Its growth on methanol was stimulated by yeast extract or vitamin-free casamino acids. The organism grew on methanol-bicarbonate, methanol-formate or formate alone as the sole carbon sources. No growth was observed on methylamine or fomaldehyde. In the presence of excess bicarbonate a maximum yield of 98 g cell material from 100 g methanol was obtained. Ribulose diphosphate carboxylase was present in the methanol-bicarbonate-grown organism at six times the specific activity of that in the succinate-grown organism.", "contents": "Utilization of methanol by rhodospirillaceae. Enrichment culture of organisms growing anaerobically in the light in methanol-bicarbonate medium resulted in isolation of strains of Rhodopseudomonas gelatinosa and Rhodopseudomonas acidophila. The pH optimum for growth on methanol for all strains tested was approximately one unit higher than for growth on carbon sources containing more than one carbon atom. At the appropriate pH, 17 strains of Rhodospirillaceae out of 39 in a culture collection grew anaerobically in the light on methanol-bicarbonate. Rhodopseudomonas acidophia strain 10050 showed the most abundant growth and was studied in more detail. Its growth on methanol was stimulated by yeast extract or vitamin-free casamino acids. The organism grew on methanol-bicarbonate, methanol-formate or formate alone as the sole carbon sources. No growth was observed on methylamine or fomaldehyde. In the presence of excess bicarbonate a maximum yield of 98 g cell material from 100 g methanol was obtained. Ribulose diphosphate carboxylase was present in the methanol-bicarbonate-grown organism at six times the specific activity of that in the succinate-grown organism."}
{"id": "PMID:239654", "title": "Study of the regulation of oxidation and CO2 assimilation in intact Nitrobacter winogradskyi cells.", "content": "1. Changes of the adenine nucleotides in resting and growing Nitrobacter winogradskyi cells were measured in connection with regulating processes during nitrite oxidation and endogenous respiration. 2. After the addition of nitrite to endogenously respiring cells the ATP pool increased strongly during the first 60 sec at the expense of the ADP pool. At this point the energy charge was approx. 0.55. After the first 90 sec the ATP pool dropped, oscillating, to a lower level. The CO2 assimilation began at this point. 3. Under a nitrogen atmosphere the AMP pool increased and the ATP pool decreased. With a value of approx. 0.17 the energy charge was extremely low. When oxygen was added the Nitrobacter cells began to oxidize stored NADH. The ATP pool increased in a few seconds whereas the AMP pool decreased. The P/O ratio of endogenously respiring cells equaled 0.6 under these conditions. 4. During the changeover from anaerobic to aerobic conditions and in the presence of nitrite the nitrite oxidation and CO2 assimilation, opposed to aerobic conditions, were inhibited at first after the nitrite addition. The changeover of the respiratory chain enzymes from a reduced to an oxidized charge and the ATP increase were delayed in comparison with experiments without nitrite. According to these findings the endogenous respiration must be almost nil while nitrite oxidizing cells are growing.", "contents": "Study of the regulation of oxidation and CO2 assimilation in intact Nitrobacter winogradskyi cells. 1. Changes of the adenine nucleotides in resting and growing Nitrobacter winogradskyi cells were measured in connection with regulating processes during nitrite oxidation and endogenous respiration. 2. After the addition of nitrite to endogenously respiring cells the ATP pool increased strongly during the first 60 sec at the expense of the ADP pool. At this point the energy charge was approx. 0.55. After the first 90 sec the ATP pool dropped, oscillating, to a lower level. The CO2 assimilation began at this point. 3. Under a nitrogen atmosphere the AMP pool increased and the ATP pool decreased. With a value of approx. 0.17 the energy charge was extremely low. When oxygen was added the Nitrobacter cells began to oxidize stored NADH. The ATP pool increased in a few seconds whereas the AMP pool decreased. The P/O ratio of endogenously respiring cells equaled 0.6 under these conditions. 4. During the changeover from anaerobic to aerobic conditions and in the presence of nitrite the nitrite oxidation and CO2 assimilation, opposed to aerobic conditions, were inhibited at first after the nitrite addition. The changeover of the respiratory chain enzymes from a reduced to an oxidized charge and the ATP increase were delayed in comparison with experiments without nitrite. According to these findings the endogenous respiration must be almost nil while nitrite oxidizing cells are growing."}
{"id": "PMID:239655", "title": "Comparative biochemistry of alpha-glucan-utilization in Pseudomonas amyloderamosa and Pseudomonas saccharophila: physiological significance of variations in the pathway.", "content": "Growth patterns on and utilization of various alpha-glucans were investigated in Pseudomonas amyloderamosa and P. saccharophila. Maltose, maltodextrins (average chain length 7 glycosyl units) and glycogen supported excellent growth of both organisms and were extensively metabolized, although glycogen utilization in P. saccharophila was preceded by a prolonged lag phase. P. amyloderamosa produced limited growth on amylopectin and the carbohydrate was only partly degraded. It seemed likely that many of the unit chains liberated from amylopectin had a length exceeding the substrate range accepted by the maltodextrin permease (transport) system. A correlation was established between the pH of the medium and the utilization of glycogen and amylopectin for growth in P. amyloderamosa. The carbohydrates were at least partly utilizable at pH 6.0, whereas they could not support any growth at pH 6.5. Most likely, the lack of growth at the higher pH reflected the low activity of isolamylase at this pH. The enzyme patterns of maltodextrin catabolism in the two bacteria were established. Intracellularly, maltodextrin phosphorylase and 4-alpha-glucanotransferase occurred in both. Degradation of extracellular alpha-glucans was mediated by a mainly intracellular isoamylase in P. amyloderamosa, whereas P. saccharophila possessed an extracellular alpha-amylase and a firmly cell-bound pullulanase.", "contents": "Comparative biochemistry of alpha-glucan-utilization in Pseudomonas amyloderamosa and Pseudomonas saccharophila: physiological significance of variations in the pathway. Growth patterns on and utilization of various alpha-glucans were investigated in Pseudomonas amyloderamosa and P. saccharophila. Maltose, maltodextrins (average chain length 7 glycosyl units) and glycogen supported excellent growth of both organisms and were extensively metabolized, although glycogen utilization in P. saccharophila was preceded by a prolonged lag phase. P. amyloderamosa produced limited growth on amylopectin and the carbohydrate was only partly degraded. It seemed likely that many of the unit chains liberated from amylopectin had a length exceeding the substrate range accepted by the maltodextrin permease (transport) system. A correlation was established between the pH of the medium and the utilization of glycogen and amylopectin for growth in P. amyloderamosa. The carbohydrates were at least partly utilizable at pH 6.0, whereas they could not support any growth at pH 6.5. Most likely, the lack of growth at the higher pH reflected the low activity of isolamylase at this pH. The enzyme patterns of maltodextrin catabolism in the two bacteria were established. Intracellularly, maltodextrin phosphorylase and 4-alpha-glucanotransferase occurred in both. Degradation of extracellular alpha-glucans was mediated by a mainly intracellular isoamylase in P. amyloderamosa, whereas P. saccharophila possessed an extracellular alpha-amylase and a firmly cell-bound pullulanase."}
{"id": "PMID:239656", "title": "Enzymatic analysis of the pathways of glucose catabolism and gluconeogenesis in Pseudomonas citronellolis.", "content": "Extracts of Pseudomonas citronellolis cells grown on glucose or gluconate possessed all the enzymes of the Entner-Doudoroff pathway. Gluconokinase and either or both 6-phosphogluconate dehydratase and KDPG aldolase were induced by growth on these substrates. Glucose and gluconate dehydrogenases and 6-phosphofructokinase were not detected. Thus catabolism of glucose proceeds via an inducible Entner-Doudoroff pathway. Metabolism of glyceraldehyde 3-phosphate apparently proceeded via glyceraldehyde 3-phosphate dehydrogenase, phosphoglycerate kinase, phosphoglycerate mutase, enolase and pyruvate kinase. These same enzymes plus triose phosphate isomerase were present in lactate-grown cells indicating that synthesis of triose phosphates from gluconeogenic substrates also occurs via this pathway. Extracts of lactate grown-cells possessed fructose diphosphatase and phosphohexoisomerase but apparently lacked fructose diphosphate aldolase thus indicating either the presence of an aldolase with unusual properties or requirements or an alternative pathway for the conversion of triose phosphate to fructose disphosphate. Cells contained two species of glyceraldehyde 3-phosphate dehydrogenase, one an NAD-dependent enzyme which predominated when the organism was grown on glycolytic substrates and the other, an NADP-dependent enzyme which predominated when the organism was grown on gluconeogenic substrates.", "contents": "Enzymatic analysis of the pathways of glucose catabolism and gluconeogenesis in Pseudomonas citronellolis. Extracts of Pseudomonas citronellolis cells grown on glucose or gluconate possessed all the enzymes of the Entner-Doudoroff pathway. Gluconokinase and either or both 6-phosphogluconate dehydratase and KDPG aldolase were induced by growth on these substrates. Glucose and gluconate dehydrogenases and 6-phosphofructokinase were not detected. Thus catabolism of glucose proceeds via an inducible Entner-Doudoroff pathway. Metabolism of glyceraldehyde 3-phosphate apparently proceeded via glyceraldehyde 3-phosphate dehydrogenase, phosphoglycerate kinase, phosphoglycerate mutase, enolase and pyruvate kinase. These same enzymes plus triose phosphate isomerase were present in lactate-grown cells indicating that synthesis of triose phosphates from gluconeogenic substrates also occurs via this pathway. Extracts of lactate grown-cells possessed fructose diphosphatase and phosphohexoisomerase but apparently lacked fructose diphosphate aldolase thus indicating either the presence of an aldolase with unusual properties or requirements or an alternative pathway for the conversion of triose phosphate to fructose disphosphate. Cells contained two species of glyceraldehyde 3-phosphate dehydrogenase, one an NAD-dependent enzyme which predominated when the organism was grown on glycolytic substrates and the other, an NADP-dependent enzyme which predominated when the organism was grown on gluconeogenic substrates."}
{"id": "PMID:239657", "title": "Aromatic amino acid biosynthesis in Alcaligenes eutrophus H16. I. Properties and regulation of 3-deoxy-d-arabino heptulosonate 7-phosphate synthase.", "content": "Properties and regulation of 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase (DAHP-synthase), EC4.1.2.15, from Alcaligenes eutrophus H16 were investigated. DAHP synthase was unstable during manipulations such as dialysis, dilution, ammonium sulfate fractionation, chromatography on DEAE-cellulose or Sephadex G-200. For kinetic measurements Sephadex G-25 treated crude extracts were used. The enzyme was not affected by thiol reagents, EDTA or divalent metal ions. The activation energy, deltaH, amounted to 16100 cal/mole. Between pH 7.2 and pH 8.2 there was little change of enzyme activity. The Km-values for the two substrates were found to be 0.043 mM phosphoenolpyruvate and 0.055 mM erythrose-4-phosphate. DAHP-synthase was inhibited by 0.5 mM phenylalanine for 60% and by 0.5 mM tyrosine for 20%. In the presence of both amino acids cumulative inhibition occurred amounting to about 70%. No other amino acid exerted inhibitory effects. A repression of DAHP-synthase by the aromatic amino acids was not observed. Some other strains of hydrogen bacteria were included in this study. The DAHP synthase from strain 12/60/X and Corynebacterium autotrophicum 7C was unregulated. The enzyme from strain 33/X was subject to retro-tyrosine inhibition and from strain 3/2, H1 and H20 were subject to cumulative inhibition.", "contents": "Aromatic amino acid biosynthesis in Alcaligenes eutrophus H16. I. Properties and regulation of 3-deoxy-d-arabino heptulosonate 7-phosphate synthase. Properties and regulation of 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase (DAHP-synthase), EC4.1.2.15, from Alcaligenes eutrophus H16 were investigated. DAHP synthase was unstable during manipulations such as dialysis, dilution, ammonium sulfate fractionation, chromatography on DEAE-cellulose or Sephadex G-200. For kinetic measurements Sephadex G-25 treated crude extracts were used. The enzyme was not affected by thiol reagents, EDTA or divalent metal ions. The activation energy, deltaH, amounted to 16100 cal/mole. Between pH 7.2 and pH 8.2 there was little change of enzyme activity. The Km-values for the two substrates were found to be 0.043 mM phosphoenolpyruvate and 0.055 mM erythrose-4-phosphate. DAHP-synthase was inhibited by 0.5 mM phenylalanine for 60% and by 0.5 mM tyrosine for 20%. In the presence of both amino acids cumulative inhibition occurred amounting to about 70%. No other amino acid exerted inhibitory effects. A repression of DAHP-synthase by the aromatic amino acids was not observed. Some other strains of hydrogen bacteria were included in this study. The DAHP synthase from strain 12/60/X and Corynebacterium autotrophicum 7C was unregulated. The enzyme from strain 33/X was subject to retro-tyrosine inhibition and from strain 3/2, H1 and H20 were subject to cumulative inhibition."}
{"id": "PMID:239658", "title": "Nitrate reductase of Dunaliella parva: electron donor specificity and heat activation.", "content": "Nitrate reductase of the salt tolerant alga Dunaliella parva, in contrast to that of most green algae, can use NADPH as well as NADH as electron donor. Extracts of cells contained various amounts of latent nitrate reductase. The latent enzyme could be activated at 45 degrees C but only in the presence of flavine adenine dinucleotide. The heat activated enzyme did not require flavine adenine dinucleotide for activity and was fully active with NADH, NADPH or reduced flavine mononucleotide as electron donors.", "contents": "Nitrate reductase of Dunaliella parva: electron donor specificity and heat activation. Nitrate reductase of the salt tolerant alga Dunaliella parva, in contrast to that of most green algae, can use NADPH as well as NADH as electron donor. Extracts of cells contained various amounts of latent nitrate reductase. The latent enzyme could be activated at 45 degrees C but only in the presence of flavine adenine dinucleotide. The heat activated enzyme did not require flavine adenine dinucleotide for activity and was fully active with NADH, NADPH or reduced flavine mononucleotide as electron donors."}
{"id": "PMID:239659", "title": "The mechanism of swarming of Vibrio alginolyticus.", "content": "Factors leading to swarming of Vibrio alginolyticus cells on solid media were studied.  Polar flagellated rods from liquid medium develop into small colonies on solid medium.  Byproducts, accumulating in the colony area, induce at certain critical concentrations, the formation of peritrichous flagella and development of long heavily flagellated filaments which swarm away form the high by-product concentrations.  Several types of nonswarming mutants were isolated, among them, mutants which lack the capacity to form swarming-inducing pyproducts, but can be induced to swarm by byproducts of other mutants incapable of swarming.  Different compounds could replace the natural metabolic byproducts; at very low concentration these compounds induce peritrichous flagella and swarming in some of the nonswarming mutants mentioned above.  The natural metabolic byproducts accumulating in yeast-extract-peptone medium are suggested to be volatile acids belonging to the valine and isoleucine pathway.  Wild-type V. alginolyticus cells cannot swarm on certain substrates but its mutants, able to swarm on many substrates in minimal media, are easily selected.", "contents": "The mechanism of swarming of Vibrio alginolyticus. Factors leading to swarming of Vibrio alginolyticus cells on solid media were studied.  Polar flagellated rods from liquid medium develop into small colonies on solid medium.  Byproducts, accumulating in the colony area, induce at certain critical concentrations, the formation of peritrichous flagella and development of long heavily flagellated filaments which swarm away form the high by-product concentrations.  Several types of nonswarming mutants were isolated, among them, mutants which lack the capacity to form swarming-inducing pyproducts, but can be induced to swarm by byproducts of other mutants incapable of swarming.  Different compounds could replace the natural metabolic byproducts; at very low concentration these compounds induce peritrichous flagella and swarming in some of the nonswarming mutants mentioned above.  The natural metabolic byproducts accumulating in yeast-extract-peptone medium are suggested to be volatile acids belonging to the valine and isoleucine pathway.  Wild-type V. alginolyticus cells cannot swarm on certain substrates but its mutants, able to swarm on many substrates in minimal media, are easily selected."}
{"id": "PMID:239660", "title": "Ammonium uptake by nitrogen fixing bacteria I. Azotobacter vinelandii.", "content": "Both the changes in the activities of nitrogenase, glutamine synthetase and glutamate dehydrogenase and in the extracellular and intracellular NH4+ concentrations were investigated during the transition from an NH4+ free medium to one containing NH4+ ions for a continuous culture of Azotobacter vinelandii. If added in amounts causing 80-100% repression of nitrogenase, ammonium acetate, lactate and phosphate are absorbed completely, whereas chloride, sulfate and citrate are only taken up to about 80%. After about 1-2 hrs the NH4+ remaining in the medium is absorbed too, indicating the induction or activation of a new NH4+ transport system. One of the new permeases allows the uptake of citrate in the presence of sucrose. Addition of inorganic NH4+ level leads to a reversible rise in the glutamine synthetase activity which is not prevented by chloramphenicol, and to a reversible decrease in nitrogenase activity. During these measurements glutamate dehydrogenase activity remains close to zero. The intracellular NH4+ level of about 0.6 mM does not change when extracellular NH4+ is taken up and repression of nitrogenase starts.", "contents": "Ammonium uptake by nitrogen fixing bacteria I. Azotobacter vinelandii. Both the changes in the activities of nitrogenase, glutamine synthetase and glutamate dehydrogenase and in the extracellular and intracellular NH4+ concentrations were investigated during the transition from an NH4+ free medium to one containing NH4+ ions for a continuous culture of Azotobacter vinelandii. If added in amounts causing 80-100% repression of nitrogenase, ammonium acetate, lactate and phosphate are absorbed completely, whereas chloride, sulfate and citrate are only taken up to about 80%. After about 1-2 hrs the NH4+ remaining in the medium is absorbed too, indicating the induction or activation of a new NH4+ transport system. One of the new permeases allows the uptake of citrate in the presence of sucrose. Addition of inorganic NH4+ level leads to a reversible rise in the glutamine synthetase activity which is not prevented by chloramphenicol, and to a reversible decrease in nitrogenase activity. During these measurements glutamate dehydrogenase activity remains close to zero. The intracellular NH4+ level of about 0.6 mM does not change when extracellular NH4+ is taken up and repression of nitrogenase starts."}
{"id": "PMID:239661", "title": "Comparative study on hydrolases in five species of Ochromonas (chrysomonadina).", "content": "Acid phosphatase and beta-glucosidase were shown to be present in five species of Ochromonas grown in organic media (O. danica, O. malhanesis, O. munuta, O. sociabilis and Ochromonas sp. 933/4). Acid phosphatase was found to have a pH optimum at 4.0 in O. danica, and at 5.1 in the four other species. No alkaline phosphatase was found in any of the above mentioned species. Beta-glucosidase in the species studied has a pH optimum at 4.6. Low alpha-glucosidase activity was found only in O. danica. Acid phosphatase in all the five species shows an increase in activity during the logarithmic phase of growth and a decrease during the early stationary phase. Beta-glucosidase shows a similar behavior only in O. danica.", "contents": "Comparative study on hydrolases in five species of Ochromonas (chrysomonadina). Acid phosphatase and beta-glucosidase were shown to be present in five species of Ochromonas grown in organic media (O. danica, O. malhanesis, O. munuta, O. sociabilis and Ochromonas sp. 933/4). Acid phosphatase was found to have a pH optimum at 4.0 in O. danica, and at 5.1 in the four other species. No alkaline phosphatase was found in any of the above mentioned species. Beta-glucosidase in the species studied has a pH optimum at 4.6. Low alpha-glucosidase activity was found only in O. danica. Acid phosphatase in all the five species shows an increase in activity during the logarithmic phase of growth and a decrease during the early stationary phase. Beta-glucosidase shows a similar behavior only in O. danica."}
{"id": "PMID:239662", "title": "Thioridazine stimulates prolactin secretion in man.", "content": "Thioridazine, unlike most other effective antipsychotic drugs, appears to be only a weak dopamine antagonist in various regions of the brain. We decided to test, indirectly, thioridazine's effects on another brain dopaminergic system, the tuberoinfundibular tract, which regulates prolactin secretion by stimulating hypothalamic secretion of prolactin-inhibiting factor. Chlorpromazine and several other phenothiazines have been shown to stimulate prolactin secretion. Five healthy men ingested 50 mg of chlorpromazine concentrate on one occasion, and 50 mg of thioridazine concentrate on another. Both drugs noticeably stimulated prolactin secretion within two hours. It is concluded that thioridazine is a potent dopamine antagonist in the tuberoinfundibular system, and it is suggested that this system's regulation of prolactin secretion may provide a useful method for studying antipsychotic drug effects in man.", "contents": "Thioridazine stimulates prolactin secretion in man. Thioridazine, unlike most other effective antipsychotic drugs, appears to be only a weak dopamine antagonist in various regions of the brain. We decided to test, indirectly, thioridazine's effects on another brain dopaminergic system, the tuberoinfundibular tract, which regulates prolactin secretion by stimulating hypothalamic secretion of prolactin-inhibiting factor. Chlorpromazine and several other phenothiazines have been shown to stimulate prolactin secretion. Five healthy men ingested 50 mg of chlorpromazine concentrate on one occasion, and 50 mg of thioridazine concentrate on another. Both drugs noticeably stimulated prolactin secretion within two hours. It is concluded that thioridazine is a potent dopamine antagonist in the tuberoinfundibular system, and it is suggested that this system's regulation of prolactin secretion may provide a useful method for studying antipsychotic drug effects in man."}
{"id": "PMID:239663", "title": "The long-acting phenothiazines.", "content": "Injected intramuscularly, the enanthane and decanoate esters of the phenothiazine fluphenazine are an effective treatment of the disordered behavior and thinking of schizophrenia. The decanoate preparation is not only slightly longer-acting but also has a smaller incidence of side-effects that the enanthate. The major adverse effect of these medications is the high frequency of extrapyramidal system disturbance. Since the 50% rate of failure of schizophrenic outpatients to take prescribed oral medications decreases treatment failure to about 20% with the use of long-acting injectable phenothiazines, this route of administration offers an advantage in patient management particularly applicable to community mental health systems. Moreover, parenteral administration of long-acting fluphenazine may be useful for patients who do not attain effective serum levels with medication taken orally because of metabolic or absorption difficulties.", "contents": "The long-acting phenothiazines. Injected intramuscularly, the enanthane and decanoate esters of the phenothiazine fluphenazine are an effective treatment of the disordered behavior and thinking of schizophrenia. The decanoate preparation is not only slightly longer-acting but also has a smaller incidence of side-effects that the enanthate. The major adverse effect of these medications is the high frequency of extrapyramidal system disturbance. Since the 50% rate of failure of schizophrenic outpatients to take prescribed oral medications decreases treatment failure to about 20% with the use of long-acting injectable phenothiazines, this route of administration offers an advantage in patient management particularly applicable to community mental health systems. Moreover, parenteral administration of long-acting fluphenazine may be useful for patients who do not attain effective serum levels with medication taken orally because of metabolic or absorption difficulties."}
{"id": "PMID:239664", "title": "Butaperazine pharmacokinetics. Effect of dosage regimen on steady state blood levels.", "content": "Experimental evidence showed that a higher whole blood steady state drug plasma level was achieved when a patient was given medication three times a day compared to the same total daily dose once a day. In addition, evidence indicated possible enzyme induction by butaperazine in one patient. We have demonstrated that the general stochastic theory developed to investigate the pharmacokinetics of lithium carbonate \"in vivo\" has more general applicability in that it applies also to butaperazine, and facilitates interpretation of findings (without blood level data) in one other drug study.", "contents": "Butaperazine pharmacokinetics. Effect of dosage regimen on steady state blood levels. Experimental evidence showed that a higher whole blood steady state drug plasma level was achieved when a patient was given medication three times a day compared to the same total daily dose once a day. In addition, evidence indicated possible enzyme induction by butaperazine in one patient. We have demonstrated that the general stochastic theory developed to investigate the pharmacokinetics of lithium carbonate \"in vivo\" has more general applicability in that it applies also to butaperazine, and facilitates interpretation of findings (without blood level data) in one other drug study."}
{"id": "PMID:239665", "title": "Feedback of true heart rate during exposure in vivo.", "content": "Ten women with specific chronic animal phobias were treated by graded exposure in vivo in two to four two-hour treatment sessions. Sessions were divided into four balanced half-hour epochs, half with visual feedback of true heart rate plus instructions to lower heart rate during approach to phobic stimulus. All patients improved significantly from the start to end of sessions on heart rate and on subjective anxiety. Feedback of heart rate plus instructions to lower it substantially reduced heart rate during epochs of feedback, compared to non-feedback epochs without instructions, but this effect did not generalize to skin conductance or to subjective anxiety in our short-term experiment.", "contents": "Feedback of true heart rate during exposure in vivo. Ten women with specific chronic animal phobias were treated by graded exposure in vivo in two to four two-hour treatment sessions. Sessions were divided into four balanced half-hour epochs, half with visual feedback of true heart rate plus instructions to lower heart rate during approach to phobic stimulus. All patients improved significantly from the start to end of sessions on heart rate and on subjective anxiety. Feedback of heart rate plus instructions to lower it substantially reduced heart rate during epochs of feedback, compared to non-feedback epochs without instructions, but this effect did not generalize to skin conductance or to subjective anxiety in our short-term experiment."}
{"id": "PMID:239666", "title": "Comparative studies of psychotherapies.  Is it true that \"everywon has one and all must have prizes\"?", "content": "Tallies were made of outcomes of all resonably controlled comparisons of psychotherapies with each other and with other treatments.  For comparisons of psychotherapy with each other, most studies found insignificant differences in proportions of patients who improved (though most patients benefited).  This \"tie score effect\" did not apply to psychotherapies vs psychopharmacotherapies compared singly-psychotherapies did better.  Combined treatments often did better than single treatments.  Among the comparisons, only two specially beneficial matches between type of patient and type of treatment were found.  Our explanations for the usual tie score effect emphasize the common components among psychotherapies, especially the helping relationship with a therapist.  However, we believe the research does not justify the conclusion that we should randomly assign patients to treatments-research results are usually based on amount of improvement; \"amount\" may not disclose differences in quality of improvement from each treatment.", "contents": "Comparative studies of psychotherapies.  Is it true that \"everywon has one and all must have prizes\"? Tallies were made of outcomes of all resonably controlled comparisons of psychotherapies with each other and with other treatments.  For comparisons of psychotherapy with each other, most studies found insignificant differences in proportions of patients who improved (though most patients benefited).  This \"tie score effect\" did not apply to psychotherapies vs psychopharmacotherapies compared singly-psychotherapies did better.  Combined treatments often did better than single treatments.  Among the comparisons, only two specially beneficial matches between type of patient and type of treatment were found.  Our explanations for the usual tie score effect emphasize the common components among psychotherapies, especially the helping relationship with a therapist.  However, we believe the research does not justify the conclusion that we should randomly assign patients to treatments-research results are usually based on amount of improvement; \"amount\" may not disclose differences in quality of improvement from each treatment."}
{"id": "PMID:239667", "title": "[Constraints matrix for the concept of new cancerostatics with activation in optimally superacidulated carcinomatous tissue (author's transl)].", "content": "Maintained immunoreaction -- an essential factor for the prospects of healing in any type of cancer therapy -- can be warranted on principle by developing cancerostatics with substantially increased selectivity. One way to approach this goal is the synthesis of functionally masked cancerostatics the active form of which is released only in optimally superacidulated carcinomatous tissue. Used as a key element for such a liberation is a enzyme contained in the cancer cells in its highly concentrated free form. The activity curve of this enzyme must have a pronounced optimum in a span of pH equal 5 to 6. Bonding the active form of, say, an alkylizing molecular group may be glycosidic by nature. Finally, a model is outlined which duly considers the various pharmaco-kinetic aspects.", "contents": "[Constraints matrix for the concept of new cancerostatics with activation in optimally superacidulated carcinomatous tissue (author's transl)]. Maintained immunoreaction -- an essential factor for the prospects of healing in any type of cancer therapy -- can be warranted on principle by developing cancerostatics with substantially increased selectivity. One way to approach this goal is the synthesis of functionally masked cancerostatics the active form of which is released only in optimally superacidulated carcinomatous tissue. Used as a key element for such a liberation is a enzyme contained in the cancer cells in its highly concentrated free form. The activity curve of this enzyme must have a pronounced optimum in a span of pH equal 5 to 6. Bonding the active form of, say, an alkylizing molecular group may be glycosidic by nature. Finally, a model is outlined which duly considers the various pharmaco-kinetic aspects."}
{"id": "PMID:239668", "title": "Hyperkalemic periodic paralysis. Effects of potassium, exercise, glucose, and acetazolamide on blood chemistry.", "content": "Effects of strenous exercise, followed by rest, and of potassium administration on blood chemistry values were studied in two patients with hyperkalemic periodic paralysis and in normal volunteers. These procedures produced attacks of flaccid paralysis that occurred concomitantly with rapid rises in serum potassium concentrations and decreases in blood glucose and inorganic phosphate levels. With the exception of the serum potassium level which rose following exercise and potassium administration, there were no changes in the blood chemistry values of the normal volunteers. During the induced attacks of paralysis, the expired breath of the patients had a very strong odor of ketosis. Results of subsequent glucose tolerance tests were abnormal. Following 24 hour administration of acetazolamide, the studies were repeated. The drug appeared to cause lesser effects of stimuli on serum potassium levels and a stabilizing effect on blood glucose levels.", "contents": "Hyperkalemic periodic paralysis. Effects of potassium, exercise, glucose, and acetazolamide on blood chemistry. Effects of strenous exercise, followed by rest, and of potassium administration on blood chemistry values were studied in two patients with hyperkalemic periodic paralysis and in normal volunteers. These procedures produced attacks of flaccid paralysis that occurred concomitantly with rapid rises in serum potassium concentrations and decreases in blood glucose and inorganic phosphate levels. With the exception of the serum potassium level which rose following exercise and potassium administration, there were no changes in the blood chemistry values of the normal volunteers. During the induced attacks of paralysis, the expired breath of the patients had a very strong odor of ketosis. Results of subsequent glucose tolerance tests were abnormal. Following 24 hour administration of acetazolamide, the studies were repeated. The drug appeared to cause lesser effects of stimuli on serum potassium levels and a stabilizing effect on blood glucose levels."}
{"id": "PMID:239670", "title": "Intraocular irrigating solutions. Their effect on the corneal endothelium.", "content": "The effects of several intraocular irrigating solutions on the corneal endothelium of rabbit and monkey corneas were evaluated, utilizing a specular microscope perfusion system with both scanning and transmission electron microscopy. Corneas perfused with 0.9% sterile isotonic physiological saline swell at a rate of 60mum to 90mum/hr; endothelial cells separate from each other and show extensive degenerative changes. Corneas perfused with lactated Ringer solution swell at a rate of 37mum to 40mum/hr, and the endothelial cells show slower, but progressive degeneration. Corneas perfused with balanced salt solution swell at 24mum to 31mum/hr, and degenerative changes become severe only after two hours. Corneas perfused with Ringer solution containing bicarbonate, reduced glutathione, and adenosine do not increase in thickness, and there is minimal deterioration of endothelial ultrastructure for periods of up to six hours.", "contents": "Intraocular irrigating solutions. Their effect on the corneal endothelium. The effects of several intraocular irrigating solutions on the corneal endothelium of rabbit and monkey corneas were evaluated, utilizing a specular microscope perfusion system with both scanning and transmission electron microscopy. Corneas perfused with 0.9% sterile isotonic physiological saline swell at a rate of 60mum to 90mum/hr; endothelial cells separate from each other and show extensive degenerative changes. Corneas perfused with lactated Ringer solution swell at a rate of 37mum to 40mum/hr, and the endothelial cells show slower, but progressive degeneration. Corneas perfused with balanced salt solution swell at 24mum to 31mum/hr, and degenerative changes become severe only after two hours. Corneas perfused with Ringer solution containing bicarbonate, reduced glutathione, and adenosine do not increase in thickness, and there is minimal deterioration of endothelial ultrastructure for periods of up to six hours."}
{"id": "PMID:239671", "title": "The applied surgical anatomy of the peritoneal fascia of the groin and the \"secondary\" internal inguinal ring.", "content": "The preperitoneal fascia of the groin is distinct from the transversalis fascia, although often mistaken for it. This distinction, and other special features of this fascia in the inguen, are more readily appreciated in the course of the preperitoneal approach than by the conventional transinguinal approach. Certain features of this fascia which are of practical surgical significance are emphasized, especially those concerning operations for hernias, hydroceles, or undescended testes in infancy and childhood. These special features include the preperitoneal fascial ring or secondary internal ring, which appears to have been confused in the past with the transversalis fascial opening or internal ring proper. Other features concerning the relative merits of the preperitoneal approach to groin hernias as opposed to the conventional transinguinal approach are discussed.", "contents": "The applied surgical anatomy of the peritoneal fascia of the groin and the \"secondary\" internal inguinal ring. The preperitoneal fascia of the groin is distinct from the transversalis fascia, although often mistaken for it. This distinction, and other special features of this fascia in the inguen, are more readily appreciated in the course of the preperitoneal approach than by the conventional transinguinal approach. Certain features of this fascia which are of practical surgical significance are emphasized, especially those concerning operations for hernias, hydroceles, or undescended testes in infancy and childhood. These special features include the preperitoneal fascial ring or secondary internal ring, which appears to have been confused in the past with the transversalis fascial opening or internal ring proper. Other features concerning the relative merits of the preperitoneal approach to groin hernias as opposed to the conventional transinguinal approach are discussed."}
{"id": "PMID:239672", "title": "The effects of cosmic particle radiation on pocket mice aboard Apollo XVII: IV. engineering aspects of the experiment and results of animal tests.", "content": "A closed passive system independent of support from the spacecraft or its crew was developed to house five pocket mice for their flight on Apollo XVII. The reaction of potassium superoxide with carbon dioxide and water vapor to produce oxygen provided a habitable atmosphere within the experiment package. The performance of the system and the ability of the mice to survive the key preflight tests gave reasonable assurance that to mice would also withstand the Apollo flight.", "contents": "The effects of cosmic particle radiation on pocket mice aboard Apollo XVII: IV. engineering aspects of the experiment and results of animal tests. A closed passive system independent of support from the spacecraft or its crew was developed to house five pocket mice for their flight on Apollo XVII. The reaction of potassium superoxide with carbon dioxide and water vapor to produce oxygen provided a habitable atmosphere within the experiment package. The performance of the system and the ability of the mice to survive the key preflight tests gave reasonable assurance that to mice would also withstand the Apollo flight."}
{"id": "PMID:239676", "title": "Interactions of urdine diphosphate glucose dehydrogenase with the inhibitor urdine diphosphate xylose.", "content": "1. UDP-xylose and UDP-glucose both bind to UDP-glucose dehydrogenase in the absence of NAD+, causing an enhancement of protein fluorescence. 2. The binding of UDP-xylose is pH-dependent, tighter binding being observed at pH8.2 than at pH8.7. 3. At low protein concentrations sigmiodal profiles of fluorescence enhancement are obtained on titration of the enzyme with UDP-xylose. As the protein concentration is increased the titration profiles become progressively more hypebolic in shape. 4. The markedly different titration profiles obtained on titrating enzyme and the enzyme-NAD+ complex with UDP-xylose suggests a conformational difference between these two species 5. NAD+ lowere the apparent affinity of the enzyme for UDP-xylose. 6. There is no change in the apparent moleculare weight of UDP-glucose dehydrogenase on binging UDP-xylose. 7. Protein modification by either diethyl pyrocarbonate or 5, 5'-dithiobis-(2-nitrobenzoate) does not \"desensitize\" the enzyme with respect to the inhibition by UDP-xylose. 8. UDP-xylose lowers the affinity of the enzyme for NADG. 9. It is suggested that UDP-xylose is acting as a substrate analogue of UDP-glucose and causes protein-conformational changes on binding to the enzyme.", "contents": "Interactions of urdine diphosphate glucose dehydrogenase with the inhibitor urdine diphosphate xylose. 1. UDP-xylose and UDP-glucose both bind to UDP-glucose dehydrogenase in the absence of NAD+, causing an enhancement of protein fluorescence. 2. The binding of UDP-xylose is pH-dependent, tighter binding being observed at pH8.2 than at pH8.7. 3. At low protein concentrations sigmiodal profiles of fluorescence enhancement are obtained on titration of the enzyme with UDP-xylose. As the protein concentration is increased the titration profiles become progressively more hypebolic in shape. 4. The markedly different titration profiles obtained on titrating enzyme and the enzyme-NAD+ complex with UDP-xylose suggests a conformational difference between these two species 5. NAD+ lowere the apparent affinity of the enzyme for UDP-xylose. 6. There is no change in the apparent moleculare weight of UDP-glucose dehydrogenase on binging UDP-xylose. 7. Protein modification by either diethyl pyrocarbonate or 5, 5'-dithiobis-(2-nitrobenzoate) does not \"desensitize\" the enzyme with respect to the inhibition by UDP-xylose. 8. UDP-xylose lowers the affinity of the enzyme for NADG. 9. It is suggested that UDP-xylose is acting as a substrate analogue of UDP-glucose and causes protein-conformational changes on binding to the enzyme."}
{"id": "PMID:239677", "title": "Properties of catechol O-methyltransferases from brain and liver of rat and human.", "content": "Kinetic and electrophoretic properties of catechol O-methyltransferases (EC 2.1.1.6) from brain and liver were studied. The enzyme of either rat or human tissues exhibited a single molecular form when subjected to electrophoresis at pH7.9. At pH9 a second, apparently oxidized, form was detected. Isoelectric-focusing experiments also indicated only one enzyme form, which was identical from extracts of brain and liver of each species (pI = 5.2 for rat, 5.5 for human). Similarities between brain and liver catechol O-methyltransferase of a given species were also demonstrated by kinetic parameters, meta/para ratios of products, and inhibitor potencies. Human catechol O-methyltransferase exhibited lower Km values than did the rat enzyme for S-adenosyl-L-methionine, dopamine and dihydroxybenzoic acid. Adrenochrome inhibited both rat and human enzyme. It was concluded (1) that only a single enzyme form could be demonstrated in the physiological pH region; (2) that catechol O-methyltransferase of brain could not be distinguished from the liver enzyme of the same species; and (3) that species differences exist between the enzymes of rat and human tissues.", "contents": "Properties of catechol O-methyltransferases from brain and liver of rat and human. Kinetic and electrophoretic properties of catechol O-methyltransferases (EC 2.1.1.6) from brain and liver were studied. The enzyme of either rat or human tissues exhibited a single molecular form when subjected to electrophoresis at pH7.9. At pH9 a second, apparently oxidized, form was detected. Isoelectric-focusing experiments also indicated only one enzyme form, which was identical from extracts of brain and liver of each species (pI = 5.2 for rat, 5.5 for human). Similarities between brain and liver catechol O-methyltransferase of a given species were also demonstrated by kinetic parameters, meta/para ratios of products, and inhibitor potencies. Human catechol O-methyltransferase exhibited lower Km values than did the rat enzyme for S-adenosyl-L-methionine, dopamine and dihydroxybenzoic acid. Adrenochrome inhibited both rat and human enzyme. It was concluded (1) that only a single enzyme form could be demonstrated in the physiological pH region; (2) that catechol O-methyltransferase of brain could not be distinguished from the liver enzyme of the same species; and (3) that species differences exist between the enzymes of rat and human tissues."}
{"id": "PMID:239678", "title": "Molecular charcteristics of chicken kidney arginase.", "content": "Chicken kidney contains two arginases with different sedimentation coefficients and substrate specificity. The ligher of these arginases, which hydrolyses only L-arginine, has been purified about 3000-fold. Like the \"ureotelic\" arginase, developed in chicken liver after starvation, it displays many of the properties of the arginase of the \"ureotelic\" species. This seems to exclude the possibility that ureotelism and uricotelism are characterized by a specific type of arginases. Both liver and kidney arginases are located in the mitochondrial matrix. The rate of hydrolysis of arginine thus not only depends on the arginase activity but also on the rate of transport of arginine into the matrix. This last process therefore is of regulatory significance.", "contents": "Molecular charcteristics of chicken kidney arginase. Chicken kidney contains two arginases with different sedimentation coefficients and substrate specificity. The ligher of these arginases, which hydrolyses only L-arginine, has been purified about 3000-fold. Like the \"ureotelic\" arginase, developed in chicken liver after starvation, it displays many of the properties of the arginase of the \"ureotelic\" species. This seems to exclude the possibility that ureotelism and uricotelism are characterized by a specific type of arginases. Both liver and kidney arginases are located in the mitochondrial matrix. The rate of hydrolysis of arginine thus not only depends on the arginase activity but also on the rate of transport of arginine into the matrix. This last process therefore is of regulatory significance."}
{"id": "PMID:239679", "title": "Characterization of a plasmin-digest fragment of rabbit immunoglobulin gamma that binds antigen and complement.", "content": "Rabbit immunoglobulin gamma (IgG) was digested with plasmin after being left for 15 min at pH2.5, 30 degrees C followed by a rapid increase in the pH to 7. The fragment antigen and complement binding (Facb) was isolated and characterized chemically and biologically. Sequence studies showed that the C-terminal quarter of the heavy chain had been removed, the split occurring at a lysine-alanine bond in the sequence Thr-Ile-Ser-Lys-Ala-Arg. The fragment Facb retained the capacity to precipitate with antigen and the precipitate caused activation of the first component of complement of the same order as that of acid-treated IgG. Both Facb and acid-treated IgG showed a fall in complement fixation relative to the native molecule of 30-40%.", "contents": "Characterization of a plasmin-digest fragment of rabbit immunoglobulin gamma that binds antigen and complement. Rabbit immunoglobulin gamma (IgG) was digested with plasmin after being left for 15 min at pH2.5, 30 degrees C followed by a rapid increase in the pH to 7. The fragment antigen and complement binding (Facb) was isolated and characterized chemically and biologically. Sequence studies showed that the C-terminal quarter of the heavy chain had been removed, the split occurring at a lysine-alanine bond in the sequence Thr-Ile-Ser-Lys-Ala-Arg. The fragment Facb retained the capacity to precipitate with antigen and the precipitate caused activation of the first component of complement of the same order as that of acid-treated IgG. Both Facb and acid-treated IgG showed a fall in complement fixation relative to the native molecule of 30-40%."}
{"id": "PMID:239680", "title": "Deoxyribonucleic acid polymerases of BHK-21/C13 cells. Partial purification and characterization of the enzymes.", "content": "DNA polymerase from BHK-21/C13 cells were separated into two species, DNA polymerase I corresponding to the heterogeneous enzyme with sedimentation coefficient of 6-8S, and DNA polymerase II, corresponding to the enzyme with sedimentation coefficient of 3.3S. DNA polymerase I was purified 114-fold and DNA polymerase II 154-fold by a simple extraction procedure followed by column chromatography on phosphocellulose and gel filtration through Sephadex G-100. The purified enzymes differed markedly in respect of pH optimum, stimulation and inhibition by K+, Km for the deoxyribonucleoside 5'-triphosphates, stability to heating at 45 degrees C, and inhibition by N-ethylmaleimide. The preferred primer-template for both enzymes was \"activated\" DNA (DNA submitted to limited degradation by pancreatic deoxyribonuclease); native or thermally denatured DNA templates were relatively very poorly copied. When certain synthetic templates were tested, substantial differences were revealed between the two enzymes. Poly[d(A-T)] was poorly used by polymerase I but was superior to \"activated\" DNA for polymerase II. Poly[d(A)]-oligo[d(pT)10] was used efficiently by polymerase I but not by polymerase II. Poly(A)-oligo[d(pT)10] was not an effective primer-template although polymerase I could use it to a limited extent when Mn2+ replaced Mg2+ in the polymerase reaction and when the temperature of incubation was lowered from 37 degrees to 30 degrees C. When only one or two or three triphosphates were supplied in the reaction mixture, the activity of polymerase I was more severly diminished than that of polymerase II.", "contents": "Deoxyribonucleic acid polymerases of BHK-21/C13 cells. Partial purification and characterization of the enzymes. DNA polymerase from BHK-21/C13 cells were separated into two species, DNA polymerase I corresponding to the heterogeneous enzyme with sedimentation coefficient of 6-8S, and DNA polymerase II, corresponding to the enzyme with sedimentation coefficient of 3.3S. DNA polymerase I was purified 114-fold and DNA polymerase II 154-fold by a simple extraction procedure followed by column chromatography on phosphocellulose and gel filtration through Sephadex G-100. The purified enzymes differed markedly in respect of pH optimum, stimulation and inhibition by K+, Km for the deoxyribonucleoside 5'-triphosphates, stability to heating at 45 degrees C, and inhibition by N-ethylmaleimide. The preferred primer-template for both enzymes was \"activated\" DNA (DNA submitted to limited degradation by pancreatic deoxyribonuclease); native or thermally denatured DNA templates were relatively very poorly copied. When certain synthetic templates were tested, substantial differences were revealed between the two enzymes. Poly[d(A-T)] was poorly used by polymerase I but was superior to \"activated\" DNA for polymerase II. Poly[d(A)]-oligo[d(pT)10] was used efficiently by polymerase I but not by polymerase II. Poly(A)-oligo[d(pT)10] was not an effective primer-template although polymerase I could use it to a limited extent when Mn2+ replaced Mg2+ in the polymerase reaction and when the temperature of incubation was lowered from 37 degrees to 30 degrees C. When only one or two or three triphosphates were supplied in the reaction mixture, the activity of polymerase I was more severly diminished than that of polymerase II."}
{"id": "PMID:239681", "title": "The electrophoretic mobilities of 5-dimethylaminoaphthalene-1-suphonyl-glycopeptides and their relation molecular weight.", "content": "The relationship between the electrophoretic mobility at pH2.1 of dansyl-glycopeptides of known composition and their molecular weight is shown to conform with a model equation previously derived for peptides. A dansyl-glycopeptide prepared from hen's-egg ovotransferrin is degraded sequentially with two glycosidases. The molecular weight of each glycopeptide intermediate formed is determined from its electrophoretic mobility. From successive molecular-weight changes, the number and type of sugar residues lost from the parent glycopeptide can be decided and the probable composition of each intermediate determined. The notion that the method has considerable application and would permit analysis of very small quantities of glycopeptides is discussed.", "contents": "The electrophoretic mobilities of 5-dimethylaminoaphthalene-1-suphonyl-glycopeptides and their relation molecular weight. The relationship between the electrophoretic mobility at pH2.1 of dansyl-glycopeptides of known composition and their molecular weight is shown to conform with a model equation previously derived for peptides. A dansyl-glycopeptide prepared from hen's-egg ovotransferrin is degraded sequentially with two glycosidases. The molecular weight of each glycopeptide intermediate formed is determined from its electrophoretic mobility. From successive molecular-weight changes, the number and type of sugar residues lost from the parent glycopeptide can be decided and the probable composition of each intermediate determined. The notion that the method has considerable application and would permit analysis of very small quantities of glycopeptides is discussed."}
{"id": "PMID:239682", "title": "Isolation and characterization of acidic structural glycoproteins in pulmonary tissues.", "content": "1. Extraction of the pleural and parenchymal regions of bovine lungs with salt and organic solvents gave powders that contained glycoproteins in addition to collagen and elastin. The contents of these glycoproteins (g/100 of powder) was 4% in pleura and 15.5% in parenchyma. 2. Attempts were made to purify these glycoproteins fromboth tissues by various methods. 3. Both tissues contained heterogeneous mixtures that were similar solubilities, had similar amino acid and carbohydrate compostions. 4. The compostions of the pulmonary glycoproteins resembled those isolated from other connective tissues by other workers.", "contents": "Isolation and characterization of acidic structural glycoproteins in pulmonary tissues. 1. Extraction of the pleural and parenchymal regions of bovine lungs with salt and organic solvents gave powders that contained glycoproteins in addition to collagen and elastin. The contents of these glycoproteins (g/100 of powder) was 4% in pleura and 15.5% in parenchyma. 2. Attempts were made to purify these glycoproteins fromboth tissues by various methods. 3. Both tissues contained heterogeneous mixtures that were similar solubilities, had similar amino acid and carbohydrate compostions. 4. The compostions of the pulmonary glycoproteins resembled those isolated from other connective tissues by other workers."}
{"id": "PMID:239683", "title": "The purification of fructose 1,6-diphosphatase from ox liver and its activation by ethylenediaminetetra-acetate.", "content": "1.A procedure for the purification of ox liver fructose 1,6-kiphosphatase is described. A number of criteria indicate that the enzyme was not subjected to any significant degree of proteolytic attack during the purification. 2. The molecular weight, amino acid composition and subunit molecular weight are reported. 3. The activation by EDTA was shown to be due to the chelation heavy metals rather than by a more complex interaction with the enzyme as had previously been suggested.", "contents": "The purification of fructose 1,6-diphosphatase from ox liver and its activation by ethylenediaminetetra-acetate. 1.A procedure for the purification of ox liver fructose 1,6-kiphosphatase is described. A number of criteria indicate that the enzyme was not subjected to any significant degree of proteolytic attack during the purification. 2. The molecular weight, amino acid composition and subunit molecular weight are reported. 3. The activation by EDTA was shown to be due to the chelation heavy metals rather than by a more complex interaction with the enzyme as had previously been suggested."}
{"id": "PMID:239684", "title": "Oxidation of polymines by diamine oxidase from human seminal plasma.", "content": "1. Diamine oxidase [amine-oxygen oxidoreductase (deaminating)(pyridoxal-containing), EC 1.4.3.6] was purified from human seminal plasma more than 1,700-fold. The enzyme appeared to be homogeneous on polyacrylamide-gel electrophoresis at two different pH values. 2. The general properties of the enzyme were comparable with those described for other diamine oxidases from different mammalian sources. The molecular weight of the enzyme was calculated to be about 182,000. 3. The enzyme had highest affinity for diamines, but polyamines spermidine and spermine were also degraded at concentrations that can be considered physiological in human semen. 3. The possible degradation of spermine by diamine oxidase in human semen in vivo may give rise to the formation of cytotoxic aldehydes that conceivably can influence the motility and survival of the spermatozoa.", "contents": "Oxidation of polymines by diamine oxidase from human seminal plasma. 1. Diamine oxidase [amine-oxygen oxidoreductase (deaminating)(pyridoxal-containing), EC 1.4.3.6] was purified from human seminal plasma more than 1,700-fold. The enzyme appeared to be homogeneous on polyacrylamide-gel electrophoresis at two different pH values. 2. The general properties of the enzyme were comparable with those described for other diamine oxidases from different mammalian sources. The molecular weight of the enzyme was calculated to be about 182,000. 3. The enzyme had highest affinity for diamines, but polyamines spermidine and spermine were also degraded at concentrations that can be considered physiological in human semen. 3. The possible degradation of spermine by diamine oxidase in human semen in vivo may give rise to the formation of cytotoxic aldehydes that conceivably can influence the motility and survival of the spermatozoa."}
{"id": "PMID:239685", "title": "The sialic acid content and isoelectric point of human kininogen.", "content": "The sialic acid content of highly purified human kininogen was found to be about 8.6 mol/mol(mol.wt. 50,000). The isoelectric point (pH 4.9 +/- 0.2) is much higher than that of bovine low-molecular-weight kininogen, but is close to that expected from the amino acid and sialic acid analyses.", "contents": "The sialic acid content and isoelectric point of human kininogen. The sialic acid content of highly purified human kininogen was found to be about 8.6 mol/mol(mol.wt. 50,000). The isoelectric point (pH 4.9 +/- 0.2) is much higher than that of bovine low-molecular-weight kininogen, but is close to that expected from the amino acid and sialic acid analyses."}
{"id": "PMID:239686", "title": "Protein kinase and phosphatases from human polymorphonuclear leucoytes.", "content": "Purified preparations of human polymorphonuclear leucocytes contain a protein kinase in the cytosol which is stimulated by cyclic AMP and cyclic IMP but not by other cyclic nucleotides. The holoenzyme had a molecular weight of 66000 estimated by gel filtration; when it was incubated with histone or cyclic AMP, it dissociated into two smaller subunits of molecular weight 45000 and 30000; the former remained cyclic AMP-sensitive, whereas the latter had become independent of added cyclic AMP. By means of substrate-affinity chromatography on histone-Sepharose 4B, cyclic [3H5AMP-binding activity (regulatory or R subunit) could be resolved into two peaks of enzyme activity, one again independent of added cyclic AMP, with a molecular weight of 30000 (catalytic or C subunit). Also by means of substrate-affinity chromatography it was possible to resolve 'specific' polymorphonuclear leukocyte histone phosphatases from 'non-specific' phosphomonesterases capable of dephosphorylating histone previously phosphorylated by the protein kinase. Specific histone phosphatase displayed greatest affinity for histone-Sepharose 4B, followed by acid p-nitrophenyl phosphatase, and the unretained acid beta-glucerophosphatase. Polymorphonuclear leucocyte histone phosphatase, purified approx. 40-fold, was further resolved from the other phosphatases by gel filtration on Sephadex G-150 from which it was eluted with apparent molecular weights of 45000 and 18700. The apparent Km values for dephosphorylation of histone are 4.3 X 10-6M and 3.6 X 10-6M. Most (69%) of cytoplasmic histone phosphatase was found in the cell sap, whereas 20% remained tightly associated with polymorphonuclear leucocyte lysosomes from which it could not be solubilized by treatments (Triton X-100, freeze-thawing) that released approx. 70% of lysosomal beta-glucuronidase or acid phosphatases. Although both soluble and particulate enzymes required 5-10 mM-Mn2 for maximal activation, and showed a pH maximum of 6.5-7.0, only the particulate enzyme was partly inhibited by ammonium molybdate. Polymorphonuclear leucocyte histone phosphatases were neither inhibited nor stimulated by those cyclic nucleotides that greatly stimulate the protein kinase of the same subcellular fraction", "contents": "Protein kinase and phosphatases from human polymorphonuclear leucoytes. Purified preparations of human polymorphonuclear leucocytes contain a protein kinase in the cytosol which is stimulated by cyclic AMP and cyclic IMP but not by other cyclic nucleotides. The holoenzyme had a molecular weight of 66000 estimated by gel filtration; when it was incubated with histone or cyclic AMP, it dissociated into two smaller subunits of molecular weight 45000 and 30000; the former remained cyclic AMP-sensitive, whereas the latter had become independent of added cyclic AMP. By means of substrate-affinity chromatography on histone-Sepharose 4B, cyclic [3H5AMP-binding activity (regulatory or R subunit) could be resolved into two peaks of enzyme activity, one again independent of added cyclic AMP, with a molecular weight of 30000 (catalytic or C subunit). Also by means of substrate-affinity chromatography it was possible to resolve 'specific' polymorphonuclear leukocyte histone phosphatases from 'non-specific' phosphomonesterases capable of dephosphorylating histone previously phosphorylated by the protein kinase. Specific histone phosphatase displayed greatest affinity for histone-Sepharose 4B, followed by acid p-nitrophenyl phosphatase, and the unretained acid beta-glucerophosphatase. Polymorphonuclear leucocyte histone phosphatase, purified approx. 40-fold, was further resolved from the other phosphatases by gel filtration on Sephadex G-150 from which it was eluted with apparent molecular weights of 45000 and 18700. The apparent Km values for dephosphorylation of histone are 4.3 X 10-6M and 3.6 X 10-6M. Most (69%) of cytoplasmic histone phosphatase was found in the cell sap, whereas 20% remained tightly associated with polymorphonuclear leucocyte lysosomes from which it could not be solubilized by treatments (Triton X-100, freeze-thawing) that released approx. 70% of lysosomal beta-glucuronidase or acid phosphatases. Although both soluble and particulate enzymes required 5-10 mM-Mn2 for maximal activation, and showed a pH maximum of 6.5-7.0, only the particulate enzyme was partly inhibited by ammonium molybdate. Polymorphonuclear leucocyte histone phosphatases were neither inhibited nor stimulated by those cyclic nucleotides that greatly stimulate the protein kinase of the same subcellular fraction"}
{"id": "PMID:239687", "title": "Evolutionary variation between a monomer and a dimer arginine kinase. Purification of the enzyme from Holothuria forskali and a comparison of some properties with that from Homarus vulgaris.", "content": "1. A purification procedure for the dimeric arginine kinase of the sea cucumber Holothuria forskali is described. 2. The enzyme has a mean molecular weight of 77250 and is composed of two equal, dissociable subunits. 3. It also shows co-operativity between substrate binding at one catalytic site to a much greater extent than the nomomeric lobster arginine kinase for which such co-operativity could not be detected unambiguously. The constants for substrate binding are reported assuming that the enzyme follows rapid-equilibrium random kinetics. From a comparison with other species, the development of co-operativity between the nucleotide- and guanidine-binding sites on one subunit is suggested to have occurred more than once in the evolution of the phosphagen kinases and is not dependent on subunit aggregation. 4. Both enzymes show similar pH profiles for thermal inactivation at 22 degrees C and have very similar stabilities. Above 40 degrees C the dimeric enzyme is much more stable than the monomer. Rate constants for heat inactivation and Arrhenius activation energies are reported. 5. The dimeric enzyme is also more stable to urea inactivation. Substrates and argininic acid all improve the stability of both enzymes. The effects of individual substrates are more distincitive with the dimeric enzymes and increase its stability to an extent that makes it about as stable as dogfish creatine kinase. In the physiological range dimerization does not seem to confer any particular advantage with respect to stability over the monomer form.", "contents": "Evolutionary variation between a monomer and a dimer arginine kinase. Purification of the enzyme from Holothuria forskali and a comparison of some properties with that from Homarus vulgaris. 1. A purification procedure for the dimeric arginine kinase of the sea cucumber Holothuria forskali is described. 2. The enzyme has a mean molecular weight of 77250 and is composed of two equal, dissociable subunits. 3. It also shows co-operativity between substrate binding at one catalytic site to a much greater extent than the nomomeric lobster arginine kinase for which such co-operativity could not be detected unambiguously. The constants for substrate binding are reported assuming that the enzyme follows rapid-equilibrium random kinetics. From a comparison with other species, the development of co-operativity between the nucleotide- and guanidine-binding sites on one subunit is suggested to have occurred more than once in the evolution of the phosphagen kinases and is not dependent on subunit aggregation. 4. Both enzymes show similar pH profiles for thermal inactivation at 22 degrees C and have very similar stabilities. Above 40 degrees C the dimeric enzyme is much more stable than the monomer. Rate constants for heat inactivation and Arrhenius activation energies are reported. 5. The dimeric enzyme is also more stable to urea inactivation. Substrates and argininic acid all improve the stability of both enzymes. The effects of individual substrates are more distincitive with the dimeric enzymes and increase its stability to an extent that makes it about as stable as dogfish creatine kinase. In the physiological range dimerization does not seem to confer any particular advantage with respect to stability over the monomer form."}
{"id": "PMID:239688", "title": "Acetyl-Coenzyme A carboxylase. Role of the prosthetic group in enzyme polymerization.", "content": "Apo-(acetyl-CoA carboxylase) completely free from the holoenzyme was prepared from biotin-deficient rat adipose tissue by using affinity chromatography. The apoenzyme does not aggregate under conditions favouring the transition of the holoenzyme to the polymeric form. Such transition is possible after the conversion of the apoenzyme into the holoenzyme in vitro, thus demonstrating the requirement of the prosthetic biotinyl group for enzyme activation.", "contents": "Acetyl-Coenzyme A carboxylase. Role of the prosthetic group in enzyme polymerization. Apo-(acetyl-CoA carboxylase) completely free from the holoenzyme was prepared from biotin-deficient rat adipose tissue by using affinity chromatography. The apoenzyme does not aggregate under conditions favouring the transition of the holoenzyme to the polymeric form. Such transition is possible after the conversion of the apoenzyme into the holoenzyme in vitro, thus demonstrating the requirement of the prosthetic biotinyl group for enzyme activation."}
{"id": "PMID:239689", "title": "Purification and properties of the pyruvate kinase of sturgeon muscle.", "content": "Pyruvate kinase was purified from sturgeon muscle in yeilds comparable with those obtained from the muscles of other species. In contrast with mammalian muscle pyruvate kinase the enzyme from sturgeon muscle gives a sigmoidal velocity curve with respect to phosphoenolpuruvate saturation, is activated by fructose 1.6-diphosphate, and is inhibited by bivalent copper ions. In these respects it is similar to the enzyme isolated from mammalian liver. The degree of interaction between phosphoenolpyruvate-binding sites is dependent on temperature.", "contents": "Purification and properties of the pyruvate kinase of sturgeon muscle. Pyruvate kinase was purified from sturgeon muscle in yeilds comparable with those obtained from the muscles of other species. In contrast with mammalian muscle pyruvate kinase the enzyme from sturgeon muscle gives a sigmoidal velocity curve with respect to phosphoenolpuruvate saturation, is activated by fructose 1.6-diphosphate, and is inhibited by bivalent copper ions. In these respects it is similar to the enzyme isolated from mammalian liver. The degree of interaction between phosphoenolpyruvate-binding sites is dependent on temperature."}
{"id": "PMID:239690", "title": "Metal-dependent proteinase of the lens. Assay, purification and properties of the bovine enzyme.", "content": "1. Two new assay methods were developed for the lens proteinase. In both, the substrate was alpha2-crystallin (a major lens protein); in the first method, the products were detected by reaction with trinitrobenzenesulphonate in the presence of SO32-, whereas in the second method, 3H-labelled substrate was used, and the products were detected as radioactivity soluble in trichloroacetic acid. 2. The neutral proteinase from bovine lens was partially purified by extraction of the lens at pH5.0 and column chromatography on hydroxyapatite and Sepharose 6B gel. 3. The purified enzyme had no detectable activity against haemoglobin, azo-casein or gamma-crystallin under optimum conditions for alpha2-crystallin. 4. The enzyme showed greatest activity and stability at pH7.5. It was reversibly inhibited by EDTA and 1,10-phenanthroline, and activated by Ca2+ and Mg2+. 5. Molecular weights obtained for the enzyme by chromatography on Sepharose 6B were approx. 500,000 in buffer of I = 0.02, and 250,000 at I = 1.02. 6. The properties of the purified lens proteinase are such as to suggest that this enzyme could account for the entire endopeptidase activity of the lens.", "contents": "Metal-dependent proteinase of the lens. Assay, purification and properties of the bovine enzyme. 1. Two new assay methods were developed for the lens proteinase. In both, the substrate was alpha2-crystallin (a major lens protein); in the first method, the products were detected by reaction with trinitrobenzenesulphonate in the presence of SO32-, whereas in the second method, 3H-labelled substrate was used, and the products were detected as radioactivity soluble in trichloroacetic acid. 2. The neutral proteinase from bovine lens was partially purified by extraction of the lens at pH5.0 and column chromatography on hydroxyapatite and Sepharose 6B gel. 3. The purified enzyme had no detectable activity against haemoglobin, azo-casein or gamma-crystallin under optimum conditions for alpha2-crystallin. 4. The enzyme showed greatest activity and stability at pH7.5. It was reversibly inhibited by EDTA and 1,10-phenanthroline, and activated by Ca2+ and Mg2+. 5. Molecular weights obtained for the enzyme by chromatography on Sepharose 6B were approx. 500,000 in buffer of I = 0.02, and 250,000 at I = 1.02. 6. The properties of the purified lens proteinase are such as to suggest that this enzyme could account for the entire endopeptidase activity of the lens."}
{"id": "PMID:239691", "title": "The microbial metabolism of C1 compounds. The cytochromes of Pseudomaonas AM1.", "content": "Pseudomonas AM1 contains cytochromes a, b and c and more than one CO-binding pigment (cytochrome a3, cytochrome c and possibly a cytochrome o). The soluble cytochrome c has been purified; its isoelectric point is low and its molecular weight is 20000. This cytochrome is reduced in whole bacteria by all oxidizable substrates at rates determined by the primary dehydrogenases. A mutant lacking cytochrome c oxidizes all substrates except methanol, ethanol and methylamine; these no longer support growth. The role of cytochrome c in electron transport in Pseudomonas AM1 is discussed.", "contents": "The microbial metabolism of C1 compounds. The cytochromes of Pseudomaonas AM1. Pseudomonas AM1 contains cytochromes a, b and c and more than one CO-binding pigment (cytochrome a3, cytochrome c and possibly a cytochrome o). The soluble cytochrome c has been purified; its isoelectric point is low and its molecular weight is 20000. This cytochrome is reduced in whole bacteria by all oxidizable substrates at rates determined by the primary dehydrogenases. A mutant lacking cytochrome c oxidizes all substrates except methanol, ethanol and methylamine; these no longer support growth. The role of cytochrome c in electron transport in Pseudomonas AM1 is discussed."}
{"id": "PMID:239692", "title": "The activities and intracellular distribution of nicotinamide-adenine dinucleotide phosphate-malate dehydrogenase, phosphoenolpyruvate carboxykinase and pyruvate carboxylase in rat, guinea-pig and rabbit tissues.", "content": "1. Measurements are presented of the activity and intracellular distribution of phosphoenolypruvate carboxykinase, pyruvate carboxylase and NADP-malate dehydrogenase in rat, guinea-pig and rabbit liver and kidney cortex, together with previously obtained measurements of these enzymes in adipose tissue. 2. In all three tissues pyruvate carboxylase activity was greatest in the rat and lowest in the rabbit. 3. Guinea pig and rabbit were very similar to each other with respect to the extramitochondrial-mitochondrial distribution of phosphoenolpyruvate carboxykinase in all three tissues. 4. NADP-malate dehydrogenase was present in all three tissues in the rat, present in kidney cortex and adipose tissue in the guinea pig and absent from all tissues examines in the rabbit.", "contents": "The activities and intracellular distribution of nicotinamide-adenine dinucleotide phosphate-malate dehydrogenase, phosphoenolpyruvate carboxykinase and pyruvate carboxylase in rat, guinea-pig and rabbit tissues. 1. Measurements are presented of the activity and intracellular distribution of phosphoenolypruvate carboxykinase, pyruvate carboxylase and NADP-malate dehydrogenase in rat, guinea-pig and rabbit liver and kidney cortex, together with previously obtained measurements of these enzymes in adipose tissue. 2. In all three tissues pyruvate carboxylase activity was greatest in the rat and lowest in the rabbit. 3. Guinea pig and rabbit were very similar to each other with respect to the extramitochondrial-mitochondrial distribution of phosphoenolpyruvate carboxykinase in all three tissues. 4. NADP-malate dehydrogenase was present in all three tissues in the rat, present in kidney cortex and adipose tissue in the guinea pig and absent from all tissues examines in the rabbit."}
{"id": "PMID:239693", "title": "The dependence on vitamin E and selenium of drug demethylation in rat liver microsomal fractions.", "content": "1. The effects of vitamin E deficiency, and of vitamin E and selenium deficiency, on rat liver microsomal aminopyrine demethylase activity were investigated. It was found that, over a wide range of substrate concentrations, the enzyme activity in preparations from deficient animals was significantly lower than that in controls. 2. Addition of antioxidants in vitro, either to the homogenization or to the assay media, was without significant effect on the depressed enzyme activity. Castration and alteration in dietary protein concentration were also without effect. The rate of oxidation of NADPH was however, lower in preparations from deficient animals. 3. Lineweaver-Burk plots of the reciprocal of enzyme activity and substrate concentration showed a higher Km value in preparations from vitamin E-deficient animals, irrespective of whether selenium was present; the Vmax. was unaffected. These parameters were unchanged when antioxidants were added in vitro. Induction with phenobarbitone and 3-methylcholanthrene showed large changes in Km value which, for preparations from vitamin E-deficient animals, was higher than that for corresponding controls. 4. Examination of the synergism between NADH and NADPH as donors of reducing equivalents for aminopyrine demethylation showed that vitamin E and selenium were only minimally involved in the phenomenon. However, both the initial rate and the extent of demethylation were significantly lower in vitamin E- and selenium-deficient preparations and both nutrients were required for the restoration of full activity. 5. The significance of these results is discussed in the light of our working hypothesis.", "contents": "The dependence on vitamin E and selenium of drug demethylation in rat liver microsomal fractions. 1. The effects of vitamin E deficiency, and of vitamin E and selenium deficiency, on rat liver microsomal aminopyrine demethylase activity were investigated. It was found that, over a wide range of substrate concentrations, the enzyme activity in preparations from deficient animals was significantly lower than that in controls. 2. Addition of antioxidants in vitro, either to the homogenization or to the assay media, was without significant effect on the depressed enzyme activity. Castration and alteration in dietary protein concentration were also without effect. The rate of oxidation of NADPH was however, lower in preparations from deficient animals. 3. Lineweaver-Burk plots of the reciprocal of enzyme activity and substrate concentration showed a higher Km value in preparations from vitamin E-deficient animals, irrespective of whether selenium was present; the Vmax. was unaffected. These parameters were unchanged when antioxidants were added in vitro. Induction with phenobarbitone and 3-methylcholanthrene showed large changes in Km value which, for preparations from vitamin E-deficient animals, was higher than that for corresponding controls. 4. Examination of the synergism between NADH and NADPH as donors of reducing equivalents for aminopyrine demethylation showed that vitamin E and selenium were only minimally involved in the phenomenon. However, both the initial rate and the extent of demethylation were significantly lower in vitamin E- and selenium-deficient preparations and both nutrients were required for the restoration of full activity. 5. The significance of these results is discussed in the light of our working hypothesis."}
{"id": "PMID:239694", "title": "Incorporation of L-[1-14C]leucine into protein by liver postmitochondrial supernatant: opposing effects of preincubated nicotinamide-adenine dinucleotide phosphate and 4-dimethylamino-3'-methylazobenzene.", "content": "Combination of preincubated drug-metabolizing medium containing NADP+ with a cell-free protein-synthesizing system resulted in marked stimulation of incorporation of L-[1-14C]leucine into protein. Addition of 4-dimethylamino-3'-methylazobenzene, present and previously preincubated in the drug-metabolizing medium, decreased this effect.", "contents": "Incorporation of L-[1-14C]leucine into protein by liver postmitochondrial supernatant: opposing effects of preincubated nicotinamide-adenine dinucleotide phosphate and 4-dimethylamino-3'-methylazobenzene. Combination of preincubated drug-metabolizing medium containing NADP+ with a cell-free protein-synthesizing system resulted in marked stimulation of incorporation of L-[1-14C]leucine into protein. Addition of 4-dimethylamino-3'-methylazobenzene, present and previously preincubated in the drug-metabolizing medium, decreased this effect."}
{"id": "PMID:239695", "title": "Purification and heterogeneity of inorganic pyrophosphatase of pig scapula cartilage.", "content": "Inorganic pyrophosphatase (pyrophosphate phosphohydrolase; EC 3.6.1.1) was purified from pig scapula cartilage by fractionation with N-cetylpyridinium chloride and (NH4)2SO4, followed by ion-exchange and gel-filtration chromatography. Enzyme preparations of high purity were obtained, with specific activities (100-400 units/mg) higher than those previously described for mammalian pyrophosphatases. The enzyme activity could be separated into several subfractions on ion-exchange columns.", "contents": "Purification and heterogeneity of inorganic pyrophosphatase of pig scapula cartilage. Inorganic pyrophosphatase (pyrophosphate phosphohydrolase; EC 3.6.1.1) was purified from pig scapula cartilage by fractionation with N-cetylpyridinium chloride and (NH4)2SO4, followed by ion-exchange and gel-filtration chromatography. Enzyme preparations of high purity were obtained, with specific activities (100-400 units/mg) higher than those previously described for mammalian pyrophosphatases. The enzyme activity could be separated into several subfractions on ion-exchange columns."}
{"id": "PMID:239696", "title": "Properties of inorganic pyrophosphatase of pig scapula cartilage.", "content": "The properties of a highly purified inorganic pyrophosphatase (pyrophosphate phosphohydrolase; EC 3.6.1.1) from pig scapula cartilage were studied. The enzyme had a molecular weight of 66 000 and a pH optimum of 7-8. It was markedly activated by magnesium, but not, or only to a much smaller degree, by other metal ions. PP1 was the only substrate found and had a Km value of 11 muM. The enzyme was not inhibited by phosphate and other inhibitors of alkaline phosphatase such as CN- minus, amino acids and theophylline; it was slightly inhibited by tartrate, formaldehyde and ammonium molybdate and strongly inhibited by F- minus, Ca2+ and other metal ions. The properties of the enzyme in the presence of concentrations of PP1 present in plasma (3.5 muM) were similar to those found at higher (2 mM) concentrations of PP1. The diphosphonates ethane-1-hydroxy-1,1-diphosphonate and dichloromethylenediphosphonate inhibited the enzyme in the presence of low PP1 concentrations. The characteristics of this enzyme are therefore similar to pyrophosphatases from other sources, such as from yeast and erythrocytes, and do not support a specific role of this enzyme in the calcification process.", "contents": "Properties of inorganic pyrophosphatase of pig scapula cartilage. The properties of a highly purified inorganic pyrophosphatase (pyrophosphate phosphohydrolase; EC 3.6.1.1) from pig scapula cartilage were studied. The enzyme had a molecular weight of 66 000 and a pH optimum of 7-8. It was markedly activated by magnesium, but not, or only to a much smaller degree, by other metal ions. PP1 was the only substrate found and had a Km value of 11 muM. The enzyme was not inhibited by phosphate and other inhibitors of alkaline phosphatase such as CN- minus, amino acids and theophylline; it was slightly inhibited by tartrate, formaldehyde and ammonium molybdate and strongly inhibited by F- minus, Ca2+ and other metal ions. The properties of the enzyme in the presence of concentrations of PP1 present in plasma (3.5 muM) were similar to those found at higher (2 mM) concentrations of PP1. The diphosphonates ethane-1-hydroxy-1,1-diphosphonate and dichloromethylenediphosphonate inhibited the enzyme in the presence of low PP1 concentrations. The characteristics of this enzyme are therefore similar to pyrophosphatases from other sources, such as from yeast and erythrocytes, and do not support a specific role of this enzyme in the calcification process."}
{"id": "PMID:239697", "title": "Poly(adenosine diphosphate ribose) polymerase in Physarum polycephalum.", "content": "1. The isolated nuclei of the slime mould Physarum polycephalum contain an enzyme that will incorporated [adenine-3H] NAD+ into an acid-insoluble product, which is shown to be poly(ADP-ribose). 2. This incorporation has an optimum pH of 8.2 and a temperature optimum below 10degreesC. 3. Optimum stimulation is given by 15 mM-Mg2+. 4. 2-Mercaptoethanol or dithiothreitol also stimulates the incorporation, the latter at an optimum concentration of about 1 mM. 5. Under optimum conditions the Km value for the reaction is 0.28 mM at 15degreesC. Nicotinamide inhibits the incorporation with a Ki of 5.7 muM. 6. Exogenous DNA stimulates the incorporation by about 100%. 7. Preincubation of the nuclei with deoxyribonuclease, but not with ribonuclease, almost completely inactivates the incorporation of NAD+. 8. The enzyme is unstable at both 0degrees and 15degreesC in the absence of dithiothreitol. The presence of dithiothreitol at a concentration of 1 mM stabilizes the enzyme at both these temperatures. 9. The activity of this enzyme per nucleus was shown in three separate experiments to fall by about one-half in early S phase and then to rise to its pre-mitotic value after about 3 h, that is in late S phase. 10. The possible physiological function of this enzyme system is discussed.", "contents": "Poly(adenosine diphosphate ribose) polymerase in Physarum polycephalum. 1. The isolated nuclei of the slime mould Physarum polycephalum contain an enzyme that will incorporated [adenine-3H] NAD+ into an acid-insoluble product, which is shown to be poly(ADP-ribose). 2. This incorporation has an optimum pH of 8.2 and a temperature optimum below 10degreesC. 3. Optimum stimulation is given by 15 mM-Mg2+. 4. 2-Mercaptoethanol or dithiothreitol also stimulates the incorporation, the latter at an optimum concentration of about 1 mM. 5. Under optimum conditions the Km value for the reaction is 0.28 mM at 15degreesC. Nicotinamide inhibits the incorporation with a Ki of 5.7 muM. 6. Exogenous DNA stimulates the incorporation by about 100%. 7. Preincubation of the nuclei with deoxyribonuclease, but not with ribonuclease, almost completely inactivates the incorporation of NAD+. 8. The enzyme is unstable at both 0degrees and 15degreesC in the absence of dithiothreitol. The presence of dithiothreitol at a concentration of 1 mM stabilizes the enzyme at both these temperatures. 9. The activity of this enzyme per nucleus was shown in three separate experiments to fall by about one-half in early S phase and then to rise to its pre-mitotic value after about 3 h, that is in late S phase. 10. The possible physiological function of this enzyme system is discussed."}
{"id": "PMID:239698", "title": "Transamidase kinetics. Amide formation in the enzymic reactions of thiol esters with amines.", "content": "1. Beta-Phenylpropionylthiocholine and N-(5-aminopentyl)-5-dimethylaminonaphthalene-1-sulphonamide (dansylcadaverine) serve as a pair of water-soluble (pH7.5) model substrates for transamidating enzymes. Amide formation could be followed directly through fluorescence measurements by monitoring the continuous extraction of the water-soluble coupling product, N-(beta-phenylpropionyl)dansylcadaverine, into n-heptane. By this procedure, the steady-state kinetics of glutamine-lysine endo-gamma-glutamyltransferase from human plasma (fibrinoligase, thrombin- and Ca2+-activated blood coagulation Factor XII) and from guinea-pig liver (liver transglutaminase) were investigated at 25 degrees C. 2. With beta-phenylpropionylthiocholine as the varied substrate, Lineweaver-Burk plots with various concentrations of dansylcadaverine intercept on the horizontal axis, suggesting that formation of the acyl-enzyme is rate limiting. 3. On the basis of functional normality of active sites, kcat. values of 1.8 s(-1) and 0.9 s(-1) were obtained for the plasma and liver gamma-glutamyltransferase respectively. The two enzymes show identical affinities for the first substrate, beta-phenylpropionylthiocholine, with Ka 4 times 10(-4) M. 4. Utilization of the second substrate, dansylcadaverine, appears to be an order of magnitude more efficient with the liver enzyme. 5. N-(5-Amino-3-thiapentyl)-5-dimethylaminonaphthalene-1-sulphonamide (dansylthiacadaverine) could be used instead of dansylcadaverine in the fluorescent kinetic system. 6. Competitive inhibition by a non-fluorescent amine substrate histamine was also evaluated.", "contents": "Transamidase kinetics. Amide formation in the enzymic reactions of thiol esters with amines. 1. Beta-Phenylpropionylthiocholine and N-(5-aminopentyl)-5-dimethylaminonaphthalene-1-sulphonamide (dansylcadaverine) serve as a pair of water-soluble (pH7.5) model substrates for transamidating enzymes. Amide formation could be followed directly through fluorescence measurements by monitoring the continuous extraction of the water-soluble coupling product, N-(beta-phenylpropionyl)dansylcadaverine, into n-heptane. By this procedure, the steady-state kinetics of glutamine-lysine endo-gamma-glutamyltransferase from human plasma (fibrinoligase, thrombin- and Ca2+-activated blood coagulation Factor XII) and from guinea-pig liver (liver transglutaminase) were investigated at 25 degrees C. 2. With beta-phenylpropionylthiocholine as the varied substrate, Lineweaver-Burk plots with various concentrations of dansylcadaverine intercept on the horizontal axis, suggesting that formation of the acyl-enzyme is rate limiting. 3. On the basis of functional normality of active sites, kcat. values of 1.8 s(-1) and 0.9 s(-1) were obtained for the plasma and liver gamma-glutamyltransferase respectively. The two enzymes show identical affinities for the first substrate, beta-phenylpropionylthiocholine, with Ka 4 times 10(-4) M. 4. Utilization of the second substrate, dansylcadaverine, appears to be an order of magnitude more efficient with the liver enzyme. 5. N-(5-Amino-3-thiapentyl)-5-dimethylaminonaphthalene-1-sulphonamide (dansylthiacadaverine) could be used instead of dansylcadaverine in the fluorescent kinetic system. 6. Competitive inhibition by a non-fluorescent amine substrate histamine was also evaluated."}
{"id": "PMID:239699", "title": "Subcellular localization and properties of mouse adrenal C19-steroid 5beta-reductase.", "content": "The localization and some characteristics of mouse adrenal C19-steroid 5 beta-reductase were determined by the incubation of subcellular fractions of mouse adrenal tissue with [7 alpha-3H]androst-4-ene-3,17-dione. This enzyme was present only in the soluble fraction and was NADPH-dependent, although a small activity in the presence of NADH was also detected. The soluble fraction also contained 3alpha-, 3beta- and a small amount of 17 beta-hydroxy steroid dehydrogenase. These and other steroid-metabolizing enzymes present in the remaining subcelluar fractions are also described briefly. To measure 5 beta-androstane-3,17-dione production by the mouse adrenal soluble fraction, all 5 beta products first had to be oxidized to 5 beta-androstane-3,17-dione, and the recovery of radio-activity between the substrate androst-4-ene-3,17-dione and product 5 beta-androstane-3,17-dione of 96.1 +/-3.2% validated this technique. C19-steroid 5 beta-reductase has a pH optimum of 6.5 and at low substrate concentrations the Km and Vmax. for 5 beta reduction of [7 alpha-3H]androst-4-ene-ene-3,17-dione was 2.22 times 10(-6) \"/- 0.48 times 10(-6) M and 450+/- 53 pmol/min per mg of protein respectively. At high substrate concentration, inhibition of the reaction occurred, which was shown to be due to increasing product concentration.", "contents": "Subcellular localization and properties of mouse adrenal C19-steroid 5beta-reductase. The localization and some characteristics of mouse adrenal C19-steroid 5 beta-reductase were determined by the incubation of subcellular fractions of mouse adrenal tissue with [7 alpha-3H]androst-4-ene-3,17-dione. This enzyme was present only in the soluble fraction and was NADPH-dependent, although a small activity in the presence of NADH was also detected. The soluble fraction also contained 3alpha-, 3beta- and a small amount of 17 beta-hydroxy steroid dehydrogenase. These and other steroid-metabolizing enzymes present in the remaining subcelluar fractions are also described briefly. To measure 5 beta-androstane-3,17-dione production by the mouse adrenal soluble fraction, all 5 beta products first had to be oxidized to 5 beta-androstane-3,17-dione, and the recovery of radio-activity between the substrate androst-4-ene-3,17-dione and product 5 beta-androstane-3,17-dione of 96.1 +/-3.2% validated this technique. C19-steroid 5 beta-reductase has a pH optimum of 6.5 and at low substrate concentrations the Km and Vmax. for 5 beta reduction of [7 alpha-3H]androst-4-ene-ene-3,17-dione was 2.22 times 10(-6) \"/- 0.48 times 10(-6) M and 450+/- 53 pmol/min per mg of protein respectively. At high substrate concentration, inhibition of the reaction occurred, which was shown to be due to increasing product concentration."}
{"id": "PMID:239700", "title": "A comparative study of some kinetic and spectral properties of guanidinated and native cytochrome c.", "content": "An investigation of the spectral and some kinetic properties of a chemically modified cytochrome c is presented. The kinetics of reduction by chromous ion and ascorbate are shown to be unchanged from that of the native molecule, as are the kinetics of NO binding. The effects of pH on the visible spectrum are discussed in terms of a possible change in the pattern of co-ordination of the molecule with changing pH.", "contents": "A comparative study of some kinetic and spectral properties of guanidinated and native cytochrome c. An investigation of the spectral and some kinetic properties of a chemically modified cytochrome c is presented. The kinetics of reduction by chromous ion and ascorbate are shown to be unchanged from that of the native molecule, as are the kinetics of NO binding. The effects of pH on the visible spectrum are discussed in terms of a possible change in the pattern of co-ordination of the molecule with changing pH."}
{"id": "PMID:239701", "title": "A deactivating conformational change induced by reduced nicotinamide-adenine dinucleotide phosphate in a Neurospora glutamate dehydrogenase.", "content": "Stopped-flow fluorescence techniques have been used to observe the formation of the binary comples of E-NADPH. At pH 7.5 there is a protein conformational change after the formation of the binary complex. This conformational change can be detected by a decrease in the fluorescence intensity of the complex at 350 nm and by an increase in its fluorescence intensity at 450 nm.", "contents": "A deactivating conformational change induced by reduced nicotinamide-adenine dinucleotide phosphate in a Neurospora glutamate dehydrogenase. Stopped-flow fluorescence techniques have been used to observe the formation of the binary comples of E-NADPH. At pH 7.5 there is a protein conformational change after the formation of the binary complex. This conformational change can be detected by a decrease in the fluorescence intensity of the complex at 350 nm and by an increase in its fluorescence intensity at 450 nm."}
{"id": "PMID:239702", "title": "Aspergillus oryzae acid proteinase. Purification and properties, and formation of pi-chymotrypsin.", "content": "An acid proteinase from Aspergillus oryzae was isolated from a commercial powder by successive (NH4)2SO4 fractionation, acetone precipitation, and ion-exchange chromatography on phosphate- and DEAE-cellulose columns. The purified enzyme was found to be homogeneous by ultracentrifuge-sedimentation analysis (S20, W equal 3.63S), but electrofocusing in polyacrylamide gels and electrophoresis at pH 3.2 revealed that it consists of two very closely migrating bands. No difference in the amino acid composition and enzymic activities of the two partially separated bands could be detected, and it was concluded that the acid proteinase exists in two molecular forms. The enzyme activates bovine trypsinogen and chymotrypsinogen at pH 3.5 (the kappacat. and Km values at 35degrees C are 11.3S- minus 1, 0.10mM and 1.14S- minus 1, 0.18mM respectively). It hydrolyses the Phe-Phe bond of the synthetic pepsin substrates Z-His-Phe-Phe-OEt (kappacat. equal 1.65S- minus 1, Km equal 0.640mM at pH 3.5, 30degrees C) and Z-Ala-Ala-Phe-Phe-OPy4Pr (kappacat. equal 0.37S- minus 1, Km equal 0.037 mM at pH2.9, 39degrees C), where Z represents benzyloxycarbonyl and OPy4Pr represents 3-(4-pyridyl)-propyl 1-ester. Activation of bovine chymotrypsinogen results from the cleavage of the Arg(15)-Ile(16) bond in the zymogen. No other cleavages were observed. The use of A. oryzae proteinase provides a simple tool for the production of pi-chymotrypsin in good yield and purity.", "contents": "Aspergillus oryzae acid proteinase. Purification and properties, and formation of pi-chymotrypsin. An acid proteinase from Aspergillus oryzae was isolated from a commercial powder by successive (NH4)2SO4 fractionation, acetone precipitation, and ion-exchange chromatography on phosphate- and DEAE-cellulose columns. The purified enzyme was found to be homogeneous by ultracentrifuge-sedimentation analysis (S20, W equal 3.63S), but electrofocusing in polyacrylamide gels and electrophoresis at pH 3.2 revealed that it consists of two very closely migrating bands. No difference in the amino acid composition and enzymic activities of the two partially separated bands could be detected, and it was concluded that the acid proteinase exists in two molecular forms. The enzyme activates bovine trypsinogen and chymotrypsinogen at pH 3.5 (the kappacat. and Km values at 35degrees C are 11.3S- minus 1, 0.10mM and 1.14S- minus 1, 0.18mM respectively). It hydrolyses the Phe-Phe bond of the synthetic pepsin substrates Z-His-Phe-Phe-OEt (kappacat. equal 1.65S- minus 1, Km equal 0.640mM at pH 3.5, 30degrees C) and Z-Ala-Ala-Phe-Phe-OPy4Pr (kappacat. equal 0.37S- minus 1, Km equal 0.037 mM at pH2.9, 39degrees C), where Z represents benzyloxycarbonyl and OPy4Pr represents 3-(4-pyridyl)-propyl 1-ester. Activation of bovine chymotrypsinogen results from the cleavage of the Arg(15)-Ile(16) bond in the zymogen. No other cleavages were observed. The use of A. oryzae proteinase provides a simple tool for the production of pi-chymotrypsin in good yield and purity."}
{"id": "PMID:239703", "title": "Physical-chemical properties of C-phycocyanin isolated from an acido-thermophilic eukaryote, Cyanidium caldarium.", "content": "C-Phycocyanin from an acido-thermophilic eukaryotic alga, Cyanidium caldarium, was characterized with respect to subunit structure, absorption spectrum and fluorescence properties and was found to be similar to C-phycocyanins from mesophilic sources. The pH-dependence of fluorescence polarization and the changes in sedimentation velocity as a function of pH, concentration and temperature indicate the presence of extremely large amounts of unusually stable 19S aggregates. It was not possible to disaggregate this phycocyanin completely to monomer under normal conditions. The amino acid composition is similar to that of phycocyanins from other thermophilic and halophilic sources. The isoelectric point of this C-phycocyanin was 5.11, an unusually high value. The properties of this C-phycocyanin suggest an increase in protein stability as its mode of adaptation to the environmental stress of high temperature.", "contents": "Physical-chemical properties of C-phycocyanin isolated from an acido-thermophilic eukaryote, Cyanidium caldarium. C-Phycocyanin from an acido-thermophilic eukaryotic alga, Cyanidium caldarium, was characterized with respect to subunit structure, absorption spectrum and fluorescence properties and was found to be similar to C-phycocyanins from mesophilic sources. The pH-dependence of fluorescence polarization and the changes in sedimentation velocity as a function of pH, concentration and temperature indicate the presence of extremely large amounts of unusually stable 19S aggregates. It was not possible to disaggregate this phycocyanin completely to monomer under normal conditions. The amino acid composition is similar to that of phycocyanins from other thermophilic and halophilic sources. The isoelectric point of this C-phycocyanin was 5.11, an unusually high value. The properties of this C-phycocyanin suggest an increase in protein stability as its mode of adaptation to the environmental stress of high temperature."}
{"id": "PMID:239704", "title": "Chemical modification of amino groups and guanidino groups of trypsin. Preparation of stable and soluble derivatives.", "content": "1. Isoionic chemical modification of amino groups of trypsin (EC 3.4.21.4) was studied for the purpose of obtaining a well-defined modified trypsin with minimum changes in physicochemical properties and with sufficient stability at neutral pH. Acetamidination with methyl acetimidate hydrochloride proceeded very rapidly at pH9.8 and 5degrees C and all 14 epsilon-amino groups were modified in 2h. The reaction was limited to epsilon-amino groups. The alpha-amino group of N-terminal isoleucine was modified only by repeated reactions in the presence of 5.5 M-guanidine or 8 M-urea. 2. The epsilon-acetamidinated derivative of beta-trypsin retained enzymic activity at values comparable with those of native enzyme tested with alpha-N-benzoyl-L-arginine ethyl ester and alpha-N-benzoyl-L-arginine p-nitroanilide as substrates; it also showed substrate activation comparable with that of native enzyme. The acetamidination of alpha-trypsin resulted in approx. 50% decrease in its esterolytic activity. 3. The epsilon-acetamidinated beta-trypsin was very stable at pH8 and 25degrees C in the absence of Ca2+. The activity of 0.04% (W/V) enzyme solution remained practically unchanged for 10h, and after 24h 90% of the activity was still retained. Possible autolytic cleavage of peptide bonds of acetamidinated enzymes was followed by N-terminal analysis by using automated Edman degradation. Only the Arg(105)-Val(106) bond was found to be cleaved to an appreciable extent. Thus beta-trypsin can be stabilized simply by complete acetamidination of epsilon-amino groups without modifying guanidino groups of arginine residues. Acetamidinated alpha-trypsin was unstable, but its inactivation at a neutral pH could not be attributed to the cleavage of a single specific peptide bond. 4. The acetamidination of the alpha-amino group of the N-terminal isoleucine results in the inactivation of esterolytic activity. However, this enzyme retained the ability to react with p-nitrophenyl p'-guanidinobenzoate. 5. It was concluded that acetamidination of beta-trypsin is a convenient method for preparing a well-defined stable and soluble trypsin derivative without appreciable change in its physical properties.", "contents": "Chemical modification of amino groups and guanidino groups of trypsin. Preparation of stable and soluble derivatives. 1. Isoionic chemical modification of amino groups of trypsin (EC 3.4.21.4) was studied for the purpose of obtaining a well-defined modified trypsin with minimum changes in physicochemical properties and with sufficient stability at neutral pH. Acetamidination with methyl acetimidate hydrochloride proceeded very rapidly at pH9.8 and 5degrees C and all 14 epsilon-amino groups were modified in 2h. The reaction was limited to epsilon-amino groups. The alpha-amino group of N-terminal isoleucine was modified only by repeated reactions in the presence of 5.5 M-guanidine or 8 M-urea. 2. The epsilon-acetamidinated derivative of beta-trypsin retained enzymic activity at values comparable with those of native enzyme tested with alpha-N-benzoyl-L-arginine ethyl ester and alpha-N-benzoyl-L-arginine p-nitroanilide as substrates; it also showed substrate activation comparable with that of native enzyme. The acetamidination of alpha-trypsin resulted in approx. 50% decrease in its esterolytic activity. 3. The epsilon-acetamidinated beta-trypsin was very stable at pH8 and 25degrees C in the absence of Ca2+. The activity of 0.04% (W/V) enzyme solution remained practically unchanged for 10h, and after 24h 90% of the activity was still retained. Possible autolytic cleavage of peptide bonds of acetamidinated enzymes was followed by N-terminal analysis by using automated Edman degradation. Only the Arg(105)-Val(106) bond was found to be cleaved to an appreciable extent. Thus beta-trypsin can be stabilized simply by complete acetamidination of epsilon-amino groups without modifying guanidino groups of arginine residues. Acetamidinated alpha-trypsin was unstable, but its inactivation at a neutral pH could not be attributed to the cleavage of a single specific peptide bond. 4. The acetamidination of the alpha-amino group of the N-terminal isoleucine results in the inactivation of esterolytic activity. However, this enzyme retained the ability to react with p-nitrophenyl p'-guanidinobenzoate. 5. It was concluded that acetamidination of beta-trypsin is a convenient method for preparing a well-defined stable and soluble trypsin derivative without appreciable change in its physical properties."}
{"id": "PMID:239705", "title": "The formation of oligoglucans linked to lipid during synthesis of beta-glucan by characterized membrane fractions isolated from peas.", "content": "Membrane fractions were obtained from peas roots by using a method that permitted the isolation of a fraction rich in relatively intact dictyosome stacks. No chemical fixatives were used. The method involved incubation of the roots with cellulase, followed by gentle homogenization and sucrose-density-gradient fractionation of the homogenate. The fractions were characterized by electron microscopy. All fractions were enzymically active in incorporating glucose from UDP-glucose into water-insoluble glycolipids containing both single glucose residues and glucose oligosaccharides. Some or all of the linkages of glucose to lipid were through phosphate esters. A substance containing glucose oligosaccharides attached to or very strongly adsorbed on to protein was also formed. The membrane fractions also incorporated glucose from UDP-glucose into alkali-soluble and alkali-insoluble beta-glucans, which like the oligosaccharides contained beta(1leads to 3) and beta-(1leads to4) linkages. The distribution of the enzymic activities and the chemical properties of the lipid-linked and protein-linked oligosaccharides suggest that they may be intermediates in beta-glucan synthesis. The synthetic activity is associated with smooth-membrane vesicles which may be derived from the plasma membrane.", "contents": "The formation of oligoglucans linked to lipid during synthesis of beta-glucan by characterized membrane fractions isolated from peas. Membrane fractions were obtained from peas roots by using a method that permitted the isolation of a fraction rich in relatively intact dictyosome stacks. No chemical fixatives were used. The method involved incubation of the roots with cellulase, followed by gentle homogenization and sucrose-density-gradient fractionation of the homogenate. The fractions were characterized by electron microscopy. All fractions were enzymically active in incorporating glucose from UDP-glucose into water-insoluble glycolipids containing both single glucose residues and glucose oligosaccharides. Some or all of the linkages of glucose to lipid were through phosphate esters. A substance containing glucose oligosaccharides attached to or very strongly adsorbed on to protein was also formed. The membrane fractions also incorporated glucose from UDP-glucose into alkali-soluble and alkali-insoluble beta-glucans, which like the oligosaccharides contained beta(1leads to 3) and beta-(1leads to4) linkages. The distribution of the enzymic activities and the chemical properties of the lipid-linked and protein-linked oligosaccharides suggest that they may be intermediates in beta-glucan synthesis. The synthetic activity is associated with smooth-membrane vesicles which may be derived from the plasma membrane."}
{"id": "PMID:239706", "title": "The effects of halothane on hepatic microsomal electron transfer.", "content": "1. The effects of halothane (CF3CHBrCl), a volatile anaesthetic agent, on electron transfer in isolated rat liver microsomal preparations were examined. 2. At halothane concentrations achieved in tissues during clinical anaesthesia (1-2mM), halothane shifts the redox equilibrium of microsomal cytochrome b5 in the presence of NADPH towards the oxidized form. Halothane accelerates stoicheiometric consumption of NADPH and O2, increases the rate of reoxidation of NADH-reduced microsomal ferrocytochrom b5, but does not affect NADPH- or NADH-cytochrome c reductase activity. The enhanced microsomal electron flow seen in the presence of halothane is not diminished by CO nor is it increased by pretreatment of the animals with phenobarbital. 3. The effects of halothane are maximum in microsomal preparations isolated from animals fed on a high-carbohydrate diet to induce stearate desaturase activity. Changes in microsomal electron transfer caused by halothane are in all cases abolished by low concentrations (1-2mM) of cyanide. Microsomal stearate desaturase activity is unaffected by halothane. 4. The first-order rate constant for oxidation of membrane-bound ferrocytochrome b5 in the absence of added substrate (k1 equals 1.5 times 10(-3)A-1) is similar to that for autoxidation of purified ferrocytochrome b5(k1 equals 7 times 10(-3)S-1) the rate of autoxidation of soluble ferrocytochrome b5 is unaffected by halothane. 5. It is concluded that the effects of halothane on microsomal electron transfer are not related to cytochrome P-450 linked metabolism but rather arise from the interaction of halothane with the cyanide-sensitive factor of the stearate desaturase pathway.", "contents": "The effects of halothane on hepatic microsomal electron transfer. 1. The effects of halothane (CF3CHBrCl), a volatile anaesthetic agent, on electron transfer in isolated rat liver microsomal preparations were examined. 2. At halothane concentrations achieved in tissues during clinical anaesthesia (1-2mM), halothane shifts the redox equilibrium of microsomal cytochrome b5 in the presence of NADPH towards the oxidized form. Halothane accelerates stoicheiometric consumption of NADPH and O2, increases the rate of reoxidation of NADH-reduced microsomal ferrocytochrom b5, but does not affect NADPH- or NADH-cytochrome c reductase activity. The enhanced microsomal electron flow seen in the presence of halothane is not diminished by CO nor is it increased by pretreatment of the animals with phenobarbital. 3. The effects of halothane are maximum in microsomal preparations isolated from animals fed on a high-carbohydrate diet to induce stearate desaturase activity. Changes in microsomal electron transfer caused by halothane are in all cases abolished by low concentrations (1-2mM) of cyanide. Microsomal stearate desaturase activity is unaffected by halothane. 4. The first-order rate constant for oxidation of membrane-bound ferrocytochrome b5 in the absence of added substrate (k1 equals 1.5 times 10(-3)A-1) is similar to that for autoxidation of purified ferrocytochrome b5(k1 equals 7 times 10(-3)S-1) the rate of autoxidation of soluble ferrocytochrome b5 is unaffected by halothane. 5. It is concluded that the effects of halothane on microsomal electron transfer are not related to cytochrome P-450 linked metabolism but rather arise from the interaction of halothane with the cyanide-sensitive factor of the stearate desaturase pathway."}
{"id": "PMID:239707", "title": "The stimulation by transmitter substances and putative transmitter substances of the net activity of phospholipase A2 of synaptic membranes of cortex of guinea-pig brain.", "content": "1. The distribution of the hydrolyses of phosphatidylcholine by phospholipase A2 and phospholipase A1, and the hydrolysis of lysophosphatidylcholine by lysophospholipase, in subcellular and subsynaptosomal fractions of cerebral cortices of guinea-pig brain, was determined. 2. Noradrenaline stimulated hydrolysis by phospholipase A2 in whole synaptosomes, synaptic membranes and fractions containing synaptic vesicles. 3. Stimulation of hydrolysis by phospholipase A2 in synaptic membranes by noradrenaline was enhanced by CaCl2, and by a mixture of ATP and MgCl2. The optimum concentration of CaCl2, in the presence of ATP and MgCl2, for stimulation by 10 muM-noradrenaline was in the range 1-10muM. The optimum concentration for ATP-2MgCl2 in the presence of 1 muM-CaCl2 was in the range 0.1-1mM. 4. Hydrolysis by phospholipase A2 of synaptic membranes was also stimulated by acetylcholine, carbamoylcholine, 5-hydroxytryptamine, dopamine (3,4-dihydroxyphenethylamine), histamine, psi-aminobutyric acid, glutamic acid and aspartic acid. With appropriate concentrations of cofactors, sigmoidal dose-response curves were obtained, half-maximum stimulations being obtained with concentrations of stimulant in the range 0.1-1muM. 5. Taurine also stimulated hydrolysis of phosphatidylcholine by phospholipase A2. There were only slight stimulations with methylamine, ethylenediamine or spermidine. No stimulation was obtained with glucagon.", "contents": "The stimulation by transmitter substances and putative transmitter substances of the net activity of phospholipase A2 of synaptic membranes of cortex of guinea-pig brain. 1. The distribution of the hydrolyses of phosphatidylcholine by phospholipase A2 and phospholipase A1, and the hydrolysis of lysophosphatidylcholine by lysophospholipase, in subcellular and subsynaptosomal fractions of cerebral cortices of guinea-pig brain, was determined. 2. Noradrenaline stimulated hydrolysis by phospholipase A2 in whole synaptosomes, synaptic membranes and fractions containing synaptic vesicles. 3. Stimulation of hydrolysis by phospholipase A2 in synaptic membranes by noradrenaline was enhanced by CaCl2, and by a mixture of ATP and MgCl2. The optimum concentration of CaCl2, in the presence of ATP and MgCl2, for stimulation by 10 muM-noradrenaline was in the range 1-10muM. The optimum concentration for ATP-2MgCl2 in the presence of 1 muM-CaCl2 was in the range 0.1-1mM. 4. Hydrolysis by phospholipase A2 of synaptic membranes was also stimulated by acetylcholine, carbamoylcholine, 5-hydroxytryptamine, dopamine (3,4-dihydroxyphenethylamine), histamine, psi-aminobutyric acid, glutamic acid and aspartic acid. With appropriate concentrations of cofactors, sigmoidal dose-response curves were obtained, half-maximum stimulations being obtained with concentrations of stimulant in the range 0.1-1muM. 5. Taurine also stimulated hydrolysis of phosphatidylcholine by phospholipase A2. There were only slight stimulations with methylamine, ethylenediamine or spermidine. No stimulation was obtained with glucagon."}
{"id": "PMID:239708", "title": "The formation of mono-N-acetylhexosamine derivatives of dolichol diphosphate by pig liver microsomal fractions.", "content": "Incubation of pig liver microsomal preparations with UDP-N[U-14C]acetylglucosamine yields a 14C-labelled lipid. The requirement for Mn2+, the pH optimum, time-dependence and the reversibility by UMP of the transferase are reported. Evidence is presented in favour of the lipid being a mixture of dolichol diphosphate N-[14C]acetylglucosamine and dolichol diphosphate N-[14C]acetylmannosamine. Available data suggest that the epimerization takes place while the hexosamine is bound in this lipid-soluble form. The N-acetylmannosamine appeared not be be released into the medium. The subfractionation of the microsomal fraction to separate transferase activity from membrane-bound beta-N-acetylglucosaminidase activity is also reported.", "contents": "The formation of mono-N-acetylhexosamine derivatives of dolichol diphosphate by pig liver microsomal fractions. Incubation of pig liver microsomal preparations with UDP-N[U-14C]acetylglucosamine yields a 14C-labelled lipid. The requirement for Mn2+, the pH optimum, time-dependence and the reversibility by UMP of the transferase are reported. Evidence is presented in favour of the lipid being a mixture of dolichol diphosphate N-[14C]acetylglucosamine and dolichol diphosphate N-[14C]acetylmannosamine. Available data suggest that the epimerization takes place while the hexosamine is bound in this lipid-soluble form. The N-acetylmannosamine appeared not be be released into the medium. The subfractionation of the microsomal fraction to separate transferase activity from membrane-bound beta-N-acetylglucosaminidase activity is also reported."}
{"id": "PMID:239728", "title": "[Effect of reserpine on the potency of alpha receptor blockers].", "content": "The influence of rather low doses of reserpine (0.125--2.0 mg/kg) on the pressor effect of noradrenaline (NA) was studied in pithed rats. In addition it was investigated whether the blocking activity of alpha-sympathicolytic agents is influenced by pretreatment with reserpine. 24 h after injection of these doses of reserpine this drug only increased the pressor effect of lower doses of NA without shifting the dose-response curve to the left. As a rule in rats pretreated with reserpine the affinity of alpha-blocking agents (derivatives of phenylethylamine and phenoxyethylamine) to alpha-adrenoceptors is not considerably altered. Only two phenylethylamine derivates substituted with a p-hydroxy group possessed considerably higher blocking activity in reserpine pretreated animals than in rats not pretreated. The increase in sensitivity of blood vessels against low doses of NA (250 pg and 1 ng) observed in rats pretreated with reserpine is abolished even by alpha-blocking substances with low affinity to alpha-adrenoceptors.", "contents": "[Effect of reserpine on the potency of alpha receptor blockers]. The influence of rather low doses of reserpine (0.125--2.0 mg/kg) on the pressor effect of noradrenaline (NA) was studied in pithed rats. In addition it was investigated whether the blocking activity of alpha-sympathicolytic agents is influenced by pretreatment with reserpine. 24 h after injection of these doses of reserpine this drug only increased the pressor effect of lower doses of NA without shifting the dose-response curve to the left. As a rule in rats pretreated with reserpine the affinity of alpha-blocking agents (derivatives of phenylethylamine and phenoxyethylamine) to alpha-adrenoceptors is not considerably altered. Only two phenylethylamine derivates substituted with a p-hydroxy group possessed considerably higher blocking activity in reserpine pretreated animals than in rats not pretreated. The increase in sensitivity of blood vessels against low doses of NA (250 pg and 1 ng) observed in rats pretreated with reserpine is abolished even by alpha-blocking substances with low affinity to alpha-adrenoceptors."}
{"id": "PMID:239729", "title": "[Bromine concentration in urine following uptake of therapeutic and suicidal doses of carbromal].", "content": "The bromine concentration in urine after ingestion of therapeutic and suicidal doses of bromodiethylacetylcarbamide (carbromal) is described. Connections with the renal elimination of sodium and chlorine are described and discussed.", "contents": "[Bromine concentration in urine following uptake of therapeutic and suicidal doses of carbromal]. The bromine concentration in urine after ingestion of therapeutic and suicidal doses of bromodiethylacetylcarbamide (carbromal) is described. Connections with the renal elimination of sodium and chlorine are described and discussed."}
{"id": "PMID:239725", "title": "Identification of neutral proteases in human neutrophil granules that degrade articular cartilage proteoglycan.", "content": "Human polymorphonuclear neutrophil (PMN) granule extract (25 mug of protein) released 60 percent of the available 35SO4 from labeled rabbit articular cartilage in 0.5 hour at neutral pH. N-acetyl-L-alanyl-L-alanyl-L-prolyl-L-alanine choloromethyl ketone (NAcAAPACK), a specific elastase inhibitor, was only minimally effective against whole granule extract, and N-alpha-tosyl-L-lysine chloromethyl ketone, which inhibits trypsin but not elastase, was completely ineffective. Preparative disc-gel electrophoresis of PMN granule extract revealed two separate regions with independent activity against 35SO4-labeled cartilage. One region contained elastases and when tested alone, was completely inhibited by NAcAAPACK. The other contained lysozyme and two esterases active against N-acetyl-L-phenylalanine-alpha-naphthol. Purified lysozyme proved inactive, suggesting that the chymotrypsin-like esterases were responsible for proteoglycan degradation by this region of the gel.", "contents": "Identification of neutral proteases in human neutrophil granules that degrade articular cartilage proteoglycan. Human polymorphonuclear neutrophil (PMN) granule extract (25 mug of protein) released 60 percent of the available 35SO4 from labeled rabbit articular cartilage in 0.5 hour at neutral pH. N-acetyl-L-alanyl-L-alanyl-L-prolyl-L-alanine choloromethyl ketone (NAcAAPACK), a specific elastase inhibitor, was only minimally effective against whole granule extract, and N-alpha-tosyl-L-lysine chloromethyl ketone, which inhibits trypsin but not elastase, was completely ineffective. Preparative disc-gel electrophoresis of PMN granule extract revealed two separate regions with independent activity against 35SO4-labeled cartilage. One region contained elastases and when tested alone, was completely inhibited by NAcAAPACK. The other contained lysozyme and two esterases active against N-acetyl-L-phenylalanine-alpha-naphthol. Purified lysozyme proved inactive, suggesting that the chymotrypsin-like esterases were responsible for proteoglycan degradation by this region of the gel."}
{"id": "PMID:239730", "title": "[Model for the continuous determination of cell metabolism].", "content": "Using the isolated heart of guinea pigs according to the method of Langendorff a new model to study the metabolism of the myocardium is described. In one modification the heart is perfused by continuous flow of Ringer-Locke-solution, and the effluent is discarded. In the other modification the effluent is used for recirculation after saturation with oxygen. The advantage of this method is the possibility to measure oxygen consumption and production of acid metabolites by using pH-electrodes in the perfusion medium before and behind the heart. For measurement, the blood micro system and the acid-base analyzer is used. Many drugs and several unknown compounds have been examined for their influence on heart metabolism and could be classified as either stimulatory, inhibitory or ineffective. It is possible to study dose-response curves of these compounds to compare various compounds and to examine the cumulative or duration effects of combinations. The site of action of a compound and thus the mode of action can be examined as was demonstrated for alpha- and beta-blockers. Perfusion of the heart with glucose-free solution permits measurement of the effect of various energy sources for intensity and duration of effect. The well-known capacity of the heart to use lipids as an energy source could be demonstrated. When a pharmacologically active compound is added to the perfusion medium, glucose consumption, production of lactic acid and of other metabolites can be determined. The results obtained in the isolated heart were confirmed by corresponding tests in the intact animal. The model is highly sensitive to several classes of drugs. In some instances amounts of less than 1 mug can be determined.", "contents": "[Model for the continuous determination of cell metabolism]. Using the isolated heart of guinea pigs according to the method of Langendorff a new model to study the metabolism of the myocardium is described. In one modification the heart is perfused by continuous flow of Ringer-Locke-solution, and the effluent is discarded. In the other modification the effluent is used for recirculation after saturation with oxygen. The advantage of this method is the possibility to measure oxygen consumption and production of acid metabolites by using pH-electrodes in the perfusion medium before and behind the heart. For measurement, the blood micro system and the acid-base analyzer is used. Many drugs and several unknown compounds have been examined for their influence on heart metabolism and could be classified as either stimulatory, inhibitory or ineffective. It is possible to study dose-response curves of these compounds to compare various compounds and to examine the cumulative or duration effects of combinations. The site of action of a compound and thus the mode of action can be examined as was demonstrated for alpha- and beta-blockers. Perfusion of the heart with glucose-free solution permits measurement of the effect of various energy sources for intensity and duration of effect. The well-known capacity of the heart to use lipids as an energy source could be demonstrated. When a pharmacologically active compound is added to the perfusion medium, glucose consumption, production of lactic acid and of other metabolites can be determined. The results obtained in the isolated heart were confirmed by corresponding tests in the intact animal. The model is highly sensitive to several classes of drugs. In some instances amounts of less than 1 mug can be determined."}
{"id": "PMID:239731", "title": "The synthesis and pharmacology of a novel benzodiazepine derivative, 1-(beta-methylsulfonylethyl)-5-(o-fluorophenyl)-7-chloro-1,3-dihydro-2H-1,4-benzodiazepin-2-one (ID-622).", "content": "The pharmacological profiles of a new benzodiazepine derivative, 1-(beta-methylsulfonylethyl)-5-(o-fluorophenyl)-7-chloro-1,3-dihydro-2H-1,4-benzodiazepin-2-one (ID-622), were shown. In anti-convulsant test, ID-622 was more potent than diazepam and medazepam when tested with pentylenetetrazol or bemegride, but was less potent than diazepam tested with strychnine or MES in mice. Taming effects of ID-622 were more potent than diazepam in both electroshock- and isolation-induced fighting mice tests, but were less potent in both septal rats and O.B. rats tests. ID-622 had only a weak influence on the spontaneous locomotor activity, and did not cause the righting reflex loss. In EEG, ID-622 increased fast activity and depressed hippocampal I-waves and amygdala after-discharge in cats. Acute toxicity of ID-622 was very low.", "contents": "The synthesis and pharmacology of a novel benzodiazepine derivative, 1-(beta-methylsulfonylethyl)-5-(o-fluorophenyl)-7-chloro-1,3-dihydro-2H-1,4-benzodiazepin-2-one (ID-622). The pharmacological profiles of a new benzodiazepine derivative, 1-(beta-methylsulfonylethyl)-5-(o-fluorophenyl)-7-chloro-1,3-dihydro-2H-1,4-benzodiazepin-2-one (ID-622), were shown. In anti-convulsant test, ID-622 was more potent than diazepam and medazepam when tested with pentylenetetrazol or bemegride, but was less potent than diazepam tested with strychnine or MES in mice. Taming effects of ID-622 were more potent than diazepam in both electroshock- and isolation-induced fighting mice tests, but were less potent in both septal rats and O.B. rats tests. ID-622 had only a weak influence on the spontaneous locomotor activity, and did not cause the righting reflex loss. In EEG, ID-622 increased fast activity and depressed hippocampal I-waves and amygdala after-discharge in cats. Acute toxicity of ID-622 was very low."}
{"id": "PMID:239732", "title": "Chemico-pharmacological studies on saponins of Panax ginseng C. A. Meyer. II. Pharmacological part.", "content": "The pharmacological properties of seven pure saponins isolated from Panax ginseng C. A. Meyer were studied. 1. The ginseng saponins showed weak toxicities in mice. Especially, Rg1, Rf and Rb 1, which contained glucose as a sugar component, were weaker in their toxicities than the rest, which contained arabinose and/or rhamnose. It was also noted that the saponins containing protopanaxadiol as sapogenin were more toxic than those containing protopanaxatriol. 2. All the saponins diminished ACh-induced contraction of the isolated ileum of the guinea pig. On the other hand high concentrations of Rb 2 caused contraction of the ileum by itself. 3. All of the saponins induced a decrease in heart rate and showed biphasic actions on the blood pressure in rats, while they little affected respiration. They caused blood pressure fall preceded by slight rise. Among them, Rg 1 showed the most prominent action and it produced a blood pressure rise with doses of 30 to 100 mg/kg. The pressor as well as depressor action was not influenced by the pretreatment with any of atropine, diphenhydramine, phentolamine and propranolol. 4. Rg 1 and Re showed vasodilator action in dogs, the potencies of which were 1/20 and 1/50 of that of papaverine, respectively. Rc and Rb 2 showed very weak vasodilator actions but Rb 1 did not. 5. Among the 7 saponins, Rd, Re and Rb 2 showed more potent hemolytic actions than those of the rest and the potencies were proportional to their toxicities. 6. Whereas single administration of Rf, Re and Rd significantly suppressed the conditioned avoidance response, repeated administration of them caused facilitation of the response. On the other hand, Rb 2 always showed very weak suppressant action. 7. Rg 1, Rf, Re and Rd significantly suppressed the fighting of mice induced by foot shock, while Rb 1, Rb 2 and Re little affected the fighting. 8. All the saponins showed antifatigue action. They markedly increased the movement after compulsory gait and the action was consistent and independent of their action on the movement before compulsory gait. 9. The saponins showed moderate depressant actions on the EEG and the behavior in cats. They were qualitatively similar in their actions, although Rg 1, Re and Rb 2 were more potent than the rest. They also suppressed EEG arousal response induced by electrical stimulation of the mid brain in cats.", "contents": "Chemico-pharmacological studies on saponins of Panax ginseng C. A. Meyer. II. Pharmacological part. The pharmacological properties of seven pure saponins isolated from Panax ginseng C. A. Meyer were studied. 1. The ginseng saponins showed weak toxicities in mice. Especially, Rg1, Rf and Rb 1, which contained glucose as a sugar component, were weaker in their toxicities than the rest, which contained arabinose and/or rhamnose. It was also noted that the saponins containing protopanaxadiol as sapogenin were more toxic than those containing protopanaxatriol. 2. All the saponins diminished ACh-induced contraction of the isolated ileum of the guinea pig. On the other hand high concentrations of Rb 2 caused contraction of the ileum by itself. 3. All of the saponins induced a decrease in heart rate and showed biphasic actions on the blood pressure in rats, while they little affected respiration. They caused blood pressure fall preceded by slight rise. Among them, Rg 1 showed the most prominent action and it produced a blood pressure rise with doses of 30 to 100 mg/kg. The pressor as well as depressor action was not influenced by the pretreatment with any of atropine, diphenhydramine, phentolamine and propranolol. 4. Rg 1 and Re showed vasodilator action in dogs, the potencies of which were 1/20 and 1/50 of that of papaverine, respectively. Rc and Rb 2 showed very weak vasodilator actions but Rb 1 did not. 5. Among the 7 saponins, Rd, Re and Rb 2 showed more potent hemolytic actions than those of the rest and the potencies were proportional to their toxicities. 6. Whereas single administration of Rf, Re and Rd significantly suppressed the conditioned avoidance response, repeated administration of them caused facilitation of the response. On the other hand, Rb 2 always showed very weak suppressant action. 7. Rg 1, Rf, Re and Rd significantly suppressed the fighting of mice induced by foot shock, while Rb 1, Rb 2 and Re little affected the fighting. 8. All the saponins showed antifatigue action. They markedly increased the movement after compulsory gait and the action was consistent and independent of their action on the movement before compulsory gait. 9. The saponins showed moderate depressant actions on the EEG and the behavior in cats. They were qualitatively similar in their actions, although Rg 1, Re and Rb 2 were more potent than the rest. They also suppressed EEG arousal response induced by electrical stimulation of the mid brain in cats."}
{"id": "PMID:239733", "title": "Pharmacological properties of n1-piperonyl-n4-3,7,11-trimethyl-2,6,10-dodecatrienyl-piperazine, a new non-anticholinergic gastric antisecretory agent.", "content": "The special and general pharmacology of N1-piperonyl-N4-3,7,11-trimethyl-2,6,10-dodecatrienylpiperazine (U-27) is reported. According to the results of the animal experiments the compound turned out to be a well tolerated gastric antisecretory drug devoid of anticholinergic activity. The compound was able to prevent hypersecretion induced by pylorus ligature in rat and guinea pig. Its duration of action was remarkable and no tolerance occurred after a repeated treatment. The compound displayed also an interesting activity on several experimental ulcers.", "contents": "Pharmacological properties of n1-piperonyl-n4-3,7,11-trimethyl-2,6,10-dodecatrienyl-piperazine, a new non-anticholinergic gastric antisecretory agent. The special and general pharmacology of N1-piperonyl-N4-3,7,11-trimethyl-2,6,10-dodecatrienylpiperazine (U-27) is reported. According to the results of the animal experiments the compound turned out to be a well tolerated gastric antisecretory drug devoid of anticholinergic activity. The compound was able to prevent hypersecretion induced by pylorus ligature in rat and guinea pig. Its duration of action was remarkable and no tolerance occurred after a repeated treatment. The compound displayed also an interesting activity on several experimental ulcers."}
{"id": "PMID:239734", "title": "[Stability of amphetaminil. 2. In vivo studies].", "content": "The metabolism of radioactively labelled alpha-phenyl-alpha-N-(beta-phenyl-isopropyl)-aminoacetonitrile (amphetaminil, AN 1-R) (tritium-labelled in the amphetamine-part, 14C-labelled in the benzaldehyde-part of the molecule) in the rat was examined. In the body amphetaminil is cleft very quickly into the original compounds of its chemical synthesis (amphetamine, benzaldehyde and hydrocyanic acid) independent of the mode of application (i.p. or oral). Blood: In the interval from 5-90 min after application of amphetaminil only 1-2 percent of the total radioactivity are received from amphetaminil. The main part of the tritium- and 14C-radioactivity is distributed among amphetamine, p-OH-amphetamineglucuronide and hippuric acid. Brain: In the brain only a minimum amount of amphetaminil can be present, if any. The share of amphetamine of the total activity amounts to more than 90 percent. Adipose tissue: In the adipose tissue the ratio of the two isotopes of the substances extracted at pH 5 is almost equal to that of the administered amphetaminil. It seems that the substance is enriched there because of its pronounced lipophilia. After i.p. application the concentration is about 12 times higher than after oral application. Urine: In the urine there could be detected amphetamine, p-OH-amphetamineglucuronide and hippuric acid but no amphetaminil.", "contents": "[Stability of amphetaminil. 2. In vivo studies]. The metabolism of radioactively labelled alpha-phenyl-alpha-N-(beta-phenyl-isopropyl)-aminoacetonitrile (amphetaminil, AN 1-R) (tritium-labelled in the amphetamine-part, 14C-labelled in the benzaldehyde-part of the molecule) in the rat was examined. In the body amphetaminil is cleft very quickly into the original compounds of its chemical synthesis (amphetamine, benzaldehyde and hydrocyanic acid) independent of the mode of application (i.p. or oral). Blood: In the interval from 5-90 min after application of amphetaminil only 1-2 percent of the total radioactivity are received from amphetaminil. The main part of the tritium- and 14C-radioactivity is distributed among amphetamine, p-OH-amphetamineglucuronide and hippuric acid. Brain: In the brain only a minimum amount of amphetaminil can be present, if any. The share of amphetamine of the total activity amounts to more than 90 percent. Adipose tissue: In the adipose tissue the ratio of the two isotopes of the substances extracted at pH 5 is almost equal to that of the administered amphetaminil. It seems that the substance is enriched there because of its pronounced lipophilia. After i.p. application the concentration is about 12 times higher than after oral application. Urine: In the urine there could be detected amphetamine, p-OH-amphetamineglucuronide and hippuric acid but no amphetaminil."}
{"id": "PMID:239735", "title": "The contribution of serum enzymes and carcinoembryonic antigen to the early diagnosis of metastatic colorectal cancer.", "content": "The evolution of metastatic colorectal cancer in patients who have had surgical treatment for a primary lesion was studied in relation the progressive changes in the blood levels of carcinembryonic antigen (CEA), to gamma glutamyl transpeptidase (GGT) and routine liver function tests (LFTs). Involvement of the liver could ofter be reliably predicted many weeks in advance of clinical diagnosis while metastases to other sites were less likely to be detected early by this test. The association of the extent of disease with the patterns of biochemical changes is discussed with reference to several illustrative examples.", "contents": "The contribution of serum enzymes and carcinoembryonic antigen to the early diagnosis of metastatic colorectal cancer. The evolution of metastatic colorectal cancer in patients who have had surgical treatment for a primary lesion was studied in relation the progressive changes in the blood levels of carcinembryonic antigen (CEA), to gamma glutamyl transpeptidase (GGT) and routine liver function tests (LFTs). Involvement of the liver could ofter be reliably predicted many weeks in advance of clinical diagnosis while metastases to other sites were less likely to be detected early by this test. The association of the extent of disease with the patterns of biochemical changes is discussed with reference to several illustrative examples."}
{"id": "PMID:239736", "title": "Extraction and preliminary characterization of a human bronchogenic carcinoma antigen.", "content": "Saline extracts of human bronchogenic tumours, soluble in 50% saturated ammonium sulphate and also fractions from Sephadex G-200 chromatography were used to raise antisera in rabbits. After absorbing the antisera with normal tissue extracts, direct Ouchterlony tests were performed against tumour (adenocarcinomata and squamous cell carcinomata) and normal extracts. A precipitin reaction was given with all 11 tumour extracts tested at a concentration of 5 mg/ml whereas all the 9 normal lung control extracts did not react at concentrations up to 100 mg/ml. The possibility that this reaction could be related to histocompatibility differences between individuals is ruled out by the fact that in two cases tumour and normal tissue were obtained from the same patient. These studies and also precipitin-inhibition experiments have confirmed the existence of antigen associated with bronchial carcinomata and have shown that, although the antigen or a cross-reacting antigen is present in normal lung tissue, the amounts are small in comparison with the amounts extracted from tumour. Antigenic activity was contained in a single absorbance peak when fractionated by Sephadex G-200 chromatography and its elution volume indicated a molecular weight of approximately 4-0 times 10(4)D. Further purification was achieved using isotachophoresis. Preliminary characterization of the antigen has shown it to be stable at pH 4-5, resistant to heating at 50 degrees C for 30 min, to migrate on immunoelectrophoresis with a cationic mobility at PH 8-5 and to be immunologically distinct from carcinoembryonic antigen.", "contents": "Extraction and preliminary characterization of a human bronchogenic carcinoma antigen. Saline extracts of human bronchogenic tumours, soluble in 50% saturated ammonium sulphate and also fractions from Sephadex G-200 chromatography were used to raise antisera in rabbits. After absorbing the antisera with normal tissue extracts, direct Ouchterlony tests were performed against tumour (adenocarcinomata and squamous cell carcinomata) and normal extracts. A precipitin reaction was given with all 11 tumour extracts tested at a concentration of 5 mg/ml whereas all the 9 normal lung control extracts did not react at concentrations up to 100 mg/ml. The possibility that this reaction could be related to histocompatibility differences between individuals is ruled out by the fact that in two cases tumour and normal tissue were obtained from the same patient. These studies and also precipitin-inhibition experiments have confirmed the existence of antigen associated with bronchial carcinomata and have shown that, although the antigen or a cross-reacting antigen is present in normal lung tissue, the amounts are small in comparison with the amounts extracted from tumour. Antigenic activity was contained in a single absorbance peak when fractionated by Sephadex G-200 chromatography and its elution volume indicated a molecular weight of approximately 4-0 times 10(4)D. Further purification was achieved using isotachophoresis. Preliminary characterization of the antigen has shown it to be stable at pH 4-5, resistant to heating at 50 degrees C for 30 min, to migrate on immunoelectrophoresis with a cationic mobility at PH 8-5 and to be immunologically distinct from carcinoembryonic antigen."}
{"id": "PMID:239738", "title": "Solar urticaria. A case with possible increase of skin mast cells.", "content": "A case of solar urticaria is described showing: (I) Action spectra for late erythema (MED), late swelling and wealing with one peak of sensitivity for erythema and wealing at 405 nm.  (2) No signs of porphyria. (3) Possibly increased skin mast cells. (4) Short-lived post-irradiation fibrin deposition. (5) Haemolysis. (6) Apparent suppression of urticaria with the antihistamine Incidal.", "contents": "Solar urticaria. A case with possible increase of skin mast cells. A case of solar urticaria is described showing: (I) Action spectra for late erythema (MED), late swelling and wealing with one peak of sensitivity for erythema and wealing at 405 nm.  (2) No signs of porphyria. (3) Possibly increased skin mast cells. (4) Short-lived post-irradiation fibrin deposition. (5) Haemolysis. (6) Apparent suppression of urticaria with the antihistamine Incidal."}
{"id": "PMID:239739", "title": "The bacteriological ecosystem of the skin of children in an African tropical envirovment (Tanzania).", "content": "Using a standardized method for sampling, the aerobic microbial flora of the skin of ninety-five children in Dar es Salaam, Tanzania, was studied qualitatively and quantitatively. The subjects comprised three groups; group A, thirty-seven normal infants (below the age of 1 year); group B, twenty-nine infants with various bacterial skin lesions; and group C, twenty-nine nursery school children between 4-5 and 7 years. The following observations were made: (I) The quantitative results indicated; (a) great variation between individuals, which was more marked among the females; (b) lower bacterial counts in infants than in older children; (c) counts were not affected by the presence of infection or state of cleanliness; (d) there were some differences between females and males and between different ethnic groups. (2) Qualitatively, the types of organisms isolated were similar to those reported elsewhere. There were differences in carrier rates of many organisms but these were most striking with Staphylococcus aureus and Staph. albus. It is concluded that there are great differences in carrier rates between persons in a tropical African environment and those studied elsewhere. These difference may be due to environmental, geographical or ethnic factors. Such observations call for more studies in this area to establish the normal flora.", "contents": "The bacteriological ecosystem of the skin of children in an African tropical envirovment (Tanzania). Using a standardized method for sampling, the aerobic microbial flora of the skin of ninety-five children in Dar es Salaam, Tanzania, was studied qualitatively and quantitatively. The subjects comprised three groups; group A, thirty-seven normal infants (below the age of 1 year); group B, twenty-nine infants with various bacterial skin lesions; and group C, twenty-nine nursery school children between 4-5 and 7 years. The following observations were made: (I) The quantitative results indicated; (a) great variation between individuals, which was more marked among the females; (b) lower bacterial counts in infants than in older children; (c) counts were not affected by the presence of infection or state of cleanliness; (d) there were some differences between females and males and between different ethnic groups. (2) Qualitatively, the types of organisms isolated were similar to those reported elsewhere. There were differences in carrier rates of many organisms but these were most striking with Staphylococcus aureus and Staph. albus. It is concluded that there are great differences in carrier rates between persons in a tropical African environment and those studied elsewhere. These difference may be due to environmental, geographical or ethnic factors. Such observations call for more studies in this area to establish the normal flora."}
{"id": "PMID:239740", "title": "Hydrolysis of plant cuticle by plant pathogens. Properties of cutinase I, cutinase II, and a nonspecific esterase isolated from Fusarium solani pisi.", "content": "The properties of the homogeneous cutinase I, cutinase II, and the nonspecific esterase isolated from the extracellular fluid of cutin-grown Fusarium solani F. pisi (R.E. Purdy and P.E. Kolattukudy (1975), Biochemistry, preceding paper in this issue) were investigated. Using tritiated apple cutin as substrate, the two cutinases showed similar substrate concentration dependence, protein concentration dependence, time course profiles, and pH dependence profiles with optimum near 10.0. Using unlabeled cutin, the rate of dihydroxyhexadecanoic acid release from apple fruit cutin by cutinase I was determined to be 4.4 mumol per min per mg. The cutinases hydrolyzed methyl hexadecanoate, cyclohexyl hexadecanoate, and to a much lesser extent hexadecyl hexadecanoate but not 9-hexadecanoyloxyheptadecane, cholesteryl hexadecanoate, or hexadecyl cinnamate. The extent of hydrolysis of these model substrates by cutinase I was at least three times that by cutinase II. The nonspecific esterase hydrolyzed all of the above esters except hexadecyl cinnamate, and did so to a much greater extent than did the cutinases. None of the enzymes hydrolyzed alpha- or beta-glucosides of p-nitrophenol. p-Nitrophenyl esters of fatty acids from C2 through C18 were used as substrates and V's and Kms were determined...", "contents": "Hydrolysis of plant cuticle by plant pathogens. Properties of cutinase I, cutinase II, and a nonspecific esterase isolated from Fusarium solani pisi. The properties of the homogeneous cutinase I, cutinase II, and the nonspecific esterase isolated from the extracellular fluid of cutin-grown Fusarium solani F. pisi (R.E. Purdy and P.E. Kolattukudy (1975), Biochemistry, preceding paper in this issue) were investigated. Using tritiated apple cutin as substrate, the two cutinases showed similar substrate concentration dependence, protein concentration dependence, time course profiles, and pH dependence profiles with optimum near 10.0. Using unlabeled cutin, the rate of dihydroxyhexadecanoic acid release from apple fruit cutin by cutinase I was determined to be 4.4 mumol per min per mg. The cutinases hydrolyzed methyl hexadecanoate, cyclohexyl hexadecanoate, and to a much lesser extent hexadecyl hexadecanoate but not 9-hexadecanoyloxyheptadecane, cholesteryl hexadecanoate, or hexadecyl cinnamate. The extent of hydrolysis of these model substrates by cutinase I was at least three times that by cutinase II. The nonspecific esterase hydrolyzed all of the above esters except hexadecyl cinnamate, and did so to a much greater extent than did the cutinases. None of the enzymes hydrolyzed alpha- or beta-glucosides of p-nitrophenol. p-Nitrophenyl esters of fatty acids from C2 through C18 were used as substrates and V's and Kms were determined..."}
{"id": "PMID:239741", "title": "Studies on deoxyribonucleases from Haemophilus influenzae on DNA agarose affinity chromatography. Two-step purification of ATP-dependent deoxyribonuclease.", "content": "In a first part of this report, purification and characterization of several nucleased from lysates of Haemophilus influenzae are described. The enzymes bind to DNA with agarose columns and are removed by elution with phosphate buffer. Among the considered enzymes, the exonucleases 1 and 3, and endonuclease, a DNA polymerase and a restriction enzyme were recovered mixed by raising the phosphate concentration from 0.1 to 0.3 M, while the ATP-dependent DNAase recovered well purified, by raising the phosphate concentration to 0.45 M. After a rechromatography, on a second DNA with agarose column, of the peak of the ATP-dependent DNAase, the specific activity tested with 3H-labeled DNA was 125 units/mg of protein, representing a 300-fold purification of the original crude extract. In a second part, we have investigated the inactivation, at various pH, of transforming DNA of Haemophilus influenzae wild strain Rd with the different eluted fractions of the column, in order to determine the importance of contamination with other enzymatic activities, and also in order to confirm the nature of theisolated enzymes with a biological method. Finally, with enzymatic extracts of mutant strain Rd com minus 56, a strain which integrates shorter than normal pieces of DNA and which is suspected to possess and \"activated specific endonuclease\" able to recognize even small conformational modifications in paired structures, we tried to detect this activity on artificially constructed heteroduplex regions in DNA.", "contents": "Studies on deoxyribonucleases from Haemophilus influenzae on DNA agarose affinity chromatography. Two-step purification of ATP-dependent deoxyribonuclease. In a first part of this report, purification and characterization of several nucleased from lysates of Haemophilus influenzae are described. The enzymes bind to DNA with agarose columns and are removed by elution with phosphate buffer. Among the considered enzymes, the exonucleases 1 and 3, and endonuclease, a DNA polymerase and a restriction enzyme were recovered mixed by raising the phosphate concentration from 0.1 to 0.3 M, while the ATP-dependent DNAase recovered well purified, by raising the phosphate concentration to 0.45 M. After a rechromatography, on a second DNA with agarose column, of the peak of the ATP-dependent DNAase, the specific activity tested with 3H-labeled DNA was 125 units/mg of protein, representing a 300-fold purification of the original crude extract. In a second part, we have investigated the inactivation, at various pH, of transforming DNA of Haemophilus influenzae wild strain Rd with the different eluted fractions of the column, in order to determine the importance of contamination with other enzymatic activities, and also in order to confirm the nature of theisolated enzymes with a biological method. Finally, with enzymatic extracts of mutant strain Rd com minus 56, a strain which integrates shorter than normal pieces of DNA and which is suspected to possess and \"activated specific endonuclease\" able to recognize even small conformational modifications in paired structures, we tried to detect this activity on artificially constructed heteroduplex regions in DNA."}
{"id": "PMID:239742", "title": "Affinity labeling of the ribonucleic acid component adjacent to the peptidyl recognition center of peptidyl transferase in Escherichia coli ribosomes.", "content": "N-Iodacetylphenylalanyl-tRNA was used as an affinity label for localizing the RNA components intimately related to the peptidyl transferase activity of Escherichia coli ribosomesmthis analogue could specifically alkylate a unique nucleotide chain of 23-S RNA. The alkylation was strongly enhanced by poly(U), and was dependent on the presence of both 50- and 30-S subunits; Chloramphenicol inhibited the reaction, wheras blasticidin S stimulated it. The alkylated RNA base was found to be adenine. The nucleotide chain attacked by N-iodoacetylphenylalanyl-tRNA seemed to be localized at or near to the peptidyl recognition center of peptidyl transferase.", "contents": "Affinity labeling of the ribonucleic acid component adjacent to the peptidyl recognition center of peptidyl transferase in Escherichia coli ribosomes. N-Iodacetylphenylalanyl-tRNA was used as an affinity label for localizing the RNA components intimately related to the peptidyl transferase activity of Escherichia coli ribosomesmthis analogue could specifically alkylate a unique nucleotide chain of 23-S RNA. The alkylation was strongly enhanced by poly(U), and was dependent on the presence of both 50- and 30-S subunits; Chloramphenicol inhibited the reaction, wheras blasticidin S stimulated it. The alkylated RNA base was found to be adenine. The nucleotide chain attacked by N-iodoacetylphenylalanyl-tRNA seemed to be localized at or near to the peptidyl recognition center of peptidyl transferase."}
{"id": "PMID:239743", "title": "ATPase and GTPase activities associated with the 5-S RNA-protein complex of Escherichia coli ribosomes.", "content": "Specific 5-S RNA-protein complexes were reconstituted from Escherichia coli 5-S RNA and 50-S ribosomal proteins. These complexes consist of 5-S RNA and two major proteins, namely E-L18 and E-L25. Analysis for enzymatic activities shows that ATP and GTP are hydrolyzed and that this hydrolysis is independent of elongation factors.", "contents": "ATPase and GTPase activities associated with the 5-S RNA-protein complex of Escherichia coli ribosomes. Specific 5-S RNA-protein complexes were reconstituted from Escherichia coli 5-S RNA and 50-S ribosomal proteins. These complexes consist of 5-S RNA and two major proteins, namely E-L18 and E-L25. Analysis for enzymatic activities shows that ATP and GTP are hydrolyzed and that this hydrolysis is independent of elongation factors."}
{"id": "PMID:239744", "title": "Alkali-induced reduction of the beta-cytochromes in purified complex III from beef heart mitochondria.", "content": "Approx. 40-50% of the cytochrome b in purified Complex III is reduced by ascorbate plus N,N,N',N'-tetramethyl-p-phenylenediamine or phenazine methosulfate at neutral pH. The remaining cytochrome b, including cytochrome b-565, is reduced by increasing the pH. The apparent pK for this reduction is between pH 10 and 11, and is more than two pH units higher than a similar alkali-induced transition in Mg-ATP particles. Alkali-induced reduction of cytochrome b occurs concomitantly with the exposure of hydrophobic tyrosine and tryptophan residues to a more hydrophilic environment. The relationship of these findings to the presence of a substrate accessibility barrier in Complex III is discussed.", "contents": "Alkali-induced reduction of the beta-cytochromes in purified complex III from beef heart mitochondria. Approx. 40-50% of the cytochrome b in purified Complex III is reduced by ascorbate plus N,N,N',N'-tetramethyl-p-phenylenediamine or phenazine methosulfate at neutral pH. The remaining cytochrome b, including cytochrome b-565, is reduced by increasing the pH. The apparent pK for this reduction is between pH 10 and 11, and is more than two pH units higher than a similar alkali-induced transition in Mg-ATP particles. Alkali-induced reduction of cytochrome b occurs concomitantly with the exposure of hydrophobic tyrosine and tryptophan residues to a more hydrophilic environment. The relationship of these findings to the presence of a substrate accessibility barrier in Complex III is discussed."}
{"id": "PMID:239745", "title": "Regulation of glucose-6-phosphate dehydrogenase in spinach chloroplasts by ribulose 1,5-diphosphate and NADPH/NADP+ ratios.", "content": "The activity of glucose-6-phosphate dehydrogenase (EC 1.1.1.49) FROM SPINACH CHLOROPLASTS IS STRONGLY REGULATED BY THE RATIO OF NADPH/NADP+, with the extent of this regulation controlled by the concentration of ribulose 1,5-diphosphate. Other metabolites of the reductive pentose phosphate cycle are far less effective in mediating the regulation of the enzyme activity by NADPH/NADP+ ratio. With a ratio of NADPH/NADP+ of 2, and a concentration of ribulose 1,5-diphosphate of 0.6 mM, the activity of the enzyme is completely inhibited. This level of ribulose 1,5-diphosphate is well within the concentration range which has been reported for unicellular green algae photosynthesizing in vivo. Ratios of NADPH/NADP+ of 2.0 have been measured for isolated spinach chloroplasts in the light and under physiological conditions. Since ribulose 1,5-diphosphate is a metabolite unique to the reductive pentose phosphate cycle and inhibits glucose-6-phosphate dehydrogenase in the presence of NADPH/NADP+ ratios found in chloroplasts in the light, it is proposed that regulation of the oxidative pentose phosphate cycle is accomplished in vivo by the levels of ribulose 1,5-diphosphate, NADPH, and NADP+. It already has been shown that several key reactions of the reductive pentose phosphate cycle in chloroplasts are regulated by levels of NADPH/NADP+ or other electron-carrying cofactors, and at least one key-regulated step, the carboxylation reaction is strongly affected by 6-phosphogluconate, the metabolic unique to the oxidative pentose phosphate cycle. Thus there is an interesting inverse regulation system in chloroplasts, in which reduced/oxidized coenzymes provide a general regulatory mechanism. The reductive cycle is activated at high NADPH/NADP+ ratios where the oxidative cycle is inhibited, and ribulose 1,5-diphosphate and 6-phosphogluconate provide further control of the cycles, each regulating the cycle in which it is not a metabolite.", "contents": "Regulation of glucose-6-phosphate dehydrogenase in spinach chloroplasts by ribulose 1,5-diphosphate and NADPH/NADP+ ratios. The activity of glucose-6-phosphate dehydrogenase (EC 1.1.1.49) FROM SPINACH CHLOROPLASTS IS STRONGLY REGULATED BY THE RATIO OF NADPH/NADP+, with the extent of this regulation controlled by the concentration of ribulose 1,5-diphosphate. Other metabolites of the reductive pentose phosphate cycle are far less effective in mediating the regulation of the enzyme activity by NADPH/NADP+ ratio. With a ratio of NADPH/NADP+ of 2, and a concentration of ribulose 1,5-diphosphate of 0.6 mM, the activity of the enzyme is completely inhibited. This level of ribulose 1,5-diphosphate is well within the concentration range which has been reported for unicellular green algae photosynthesizing in vivo. Ratios of NADPH/NADP+ of 2.0 have been measured for isolated spinach chloroplasts in the light and under physiological conditions. Since ribulose 1,5-diphosphate is a metabolite unique to the reductive pentose phosphate cycle and inhibits glucose-6-phosphate dehydrogenase in the presence of NADPH/NADP+ ratios found in chloroplasts in the light, it is proposed that regulation of the oxidative pentose phosphate cycle is accomplished in vivo by the levels of ribulose 1,5-diphosphate, NADPH, and NADP+. It already has been shown that several key reactions of the reductive pentose phosphate cycle in chloroplasts are regulated by levels of NADPH/NADP+ or other electron-carrying cofactors, and at least one key-regulated step, the carboxylation reaction is strongly affected by 6-phosphogluconate, the metabolic unique to the oxidative pentose phosphate cycle. Thus there is an interesting inverse regulation system in chloroplasts, in which reduced/oxidized coenzymes provide a general regulatory mechanism. The reductive cycle is activated at high NADPH/NADP+ ratios where the oxidative cycle is inhibited, and ribulose 1,5-diphosphate and 6-phosphogluconate provide further control of the cycles, each regulating the cycle in which it is not a metabolite."}
{"id": "PMID:239746", "title": "The role of pH in the regulation of carbon fixation in the chloroplast stroma. Studies on CO2 fixation in the light and dark.", "content": "1. The pH in the stroma and in the thylakoid space has been measured in a number of chloroplast preparations in the dark and in the light at 20 degrees C. Illumination causes a decrease of the pH in the thylakoid space by 1.5 and an increase of the pH in the stroma by almost 1 pH unit. 2. CO2 fixation is shown to be strongly dependent on the pH in the stroma. The pH optimum was 8.1, with almost zero activity below pH 7.3.Phosphoglycerate reduction, which is a partial reaction of CO2 fixation, shows very little pH dependency. 3. Low concentrations of the uncoupler m-chlorocarbonylcyanide phenylhydrazone (CCCP) inhibit CO2 fixation without affecting phosphoglycerate reduction. This  inhibition of CO2 fixation appears to be caused by reversal of light induced alkalisation in the stroma by CCCP. 4. Methylamine has a very different effect compared to CCCP. Increasing concentrations of methylamine inhibit CO2 fixation and phosphoglycerate reduction to the same extent. The light induced alkalisation of the stroma appears not to be significantly inhibited by methylamine, but the protons in the thylakoid space are neutralized. The inhibition of CO2 fixation by higher concentrations of methylamine is explained by an inhibition of photophosphorylation. It appears that methylamine does not abolish proton transport. 5. It is shown that intact chloroplasts are able to fix CO2 in the dark, yielding 3-phosphoglycerate. This requires the addition of dihydroxyacetone phosphate as precursor of ribulosemonophosphate and also to supply ATP, and the addition of oxaloacetate for reoxidation of the NADPH in the stroma. 6. Dark CO2 fixation in the presence of dihydroxyacetone phosphate and oxaloacetate has the same pH dependency as CO2 fixation in the light. This demonstrates that CO2 fixation in the dark is not possible, unless the pH in the medium is artificially raised to pH 8.8.", "contents": "The role of pH in the regulation of carbon fixation in the chloroplast stroma. Studies on CO2 fixation in the light and dark. 1. The pH in the stroma and in the thylakoid space has been measured in a number of chloroplast preparations in the dark and in the light at 20 degrees C. Illumination causes a decrease of the pH in the thylakoid space by 1.5 and an increase of the pH in the stroma by almost 1 pH unit. 2. CO2 fixation is shown to be strongly dependent on the pH in the stroma. The pH optimum was 8.1, with almost zero activity below pH 7.3.Phosphoglycerate reduction, which is a partial reaction of CO2 fixation, shows very little pH dependency. 3. Low concentrations of the uncoupler m-chlorocarbonylcyanide phenylhydrazone (CCCP) inhibit CO2 fixation without affecting phosphoglycerate reduction. This  inhibition of CO2 fixation appears to be caused by reversal of light induced alkalisation in the stroma by CCCP. 4. Methylamine has a very different effect compared to CCCP. Increasing concentrations of methylamine inhibit CO2 fixation and phosphoglycerate reduction to the same extent. The light induced alkalisation of the stroma appears not to be significantly inhibited by methylamine, but the protons in the thylakoid space are neutralized. The inhibition of CO2 fixation by higher concentrations of methylamine is explained by an inhibition of photophosphorylation. It appears that methylamine does not abolish proton transport. 5. It is shown that intact chloroplasts are able to fix CO2 in the dark, yielding 3-phosphoglycerate. This requires the addition of dihydroxyacetone phosphate as precursor of ribulosemonophosphate and also to supply ATP, and the addition of oxaloacetate for reoxidation of the NADPH in the stroma. 6. Dark CO2 fixation in the presence of dihydroxyacetone phosphate and oxaloacetate has the same pH dependency as CO2 fixation in the light. This demonstrates that CO2 fixation in the dark is not possible, unless the pH in the medium is artificially raised to pH 8.8."}
{"id": "PMID:239747", "title": "Affinity chromatography of enzyme cofactors: the separation of NAD on immobilised dehydrogenase colums.", "content": "1. Alcohol dehydrogenase (EC 1.1.1.1.) has been immobilised to aminoethyl-cellulose by glutaraldehyde, to DEAE-cellulose by an s-triazine derivative and to agarose using CNBr. Lactate dehydrogenase has been immobilised to the latter two supports. 2. Their use for affinity chromatography of NAD was compared and alcohol dehydrogenase immobilised to CNBr-activated agarose chosen for detailed study due to the efficient coupling of applied enzyme and the specific nature of binding. 3. The efficiency of coupling of alcohol dehydrogenase dropped from 94.5 to 72.2% when the applied load was increased from 18 to 54 mg/g activated agarose. Activity relative to free enzyme fell from 21 to 11%. The binding of NAD was maximal between pH 5.5 and 6. With the lowest loading of enzyme, NAD binding fell from 450 to 320 mug/g support when the linear flow rate was increased from 0.84 to 3.95 cm/min. 4. NAD was completely separated from a mixture with ATP, ADP and AMP. Separation from NMN and hydrolysed RNA and DNA was evidently possible. Immobilised alcohol dehydrogenase used for 34 binding experiments over a period of weeks maintained 60% of its original enzyme activity. 5. The method was applied to yeast NAD following mechanical disruption of yeast, clarification and either ultrafiltration or hollow-fibre dialysis to permit separate purification of macromolecules and nucleotides.", "contents": "Affinity chromatography of enzyme cofactors: the separation of NAD on immobilised dehydrogenase colums. 1. Alcohol dehydrogenase (EC 1.1.1.1.) has been immobilised to aminoethyl-cellulose by glutaraldehyde, to DEAE-cellulose by an s-triazine derivative and to agarose using CNBr. Lactate dehydrogenase has been immobilised to the latter two supports. 2. Their use for affinity chromatography of NAD was compared and alcohol dehydrogenase immobilised to CNBr-activated agarose chosen for detailed study due to the efficient coupling of applied enzyme and the specific nature of binding. 3. The efficiency of coupling of alcohol dehydrogenase dropped from 94.5 to 72.2% when the applied load was increased from 18 to 54 mg/g activated agarose. Activity relative to free enzyme fell from 21 to 11%. The binding of NAD was maximal between pH 5.5 and 6. With the lowest loading of enzyme, NAD binding fell from 450 to 320 mug/g support when the linear flow rate was increased from 0.84 to 3.95 cm/min. 4. NAD was completely separated from a mixture with ATP, ADP and AMP. Separation from NMN and hydrolysed RNA and DNA was evidently possible. Immobilised alcohol dehydrogenase used for 34 binding experiments over a period of weeks maintained 60% of its original enzyme activity. 5. The method was applied to yeast NAD following mechanical disruption of yeast, clarification and either ultrafiltration or hollow-fibre dialysis to permit separate purification of macromolecules and nucleotides."}
{"id": "PMID:239748", "title": "Partial purification and properties of thiamine pyrophosphokinase from pig brain.", "content": "Pig brain thiamine pyrophosphokinase (ATP: thiamine pyrophosphotransferase, EC 2.7.6.2) was purified 260-fold over extracts of brain acetone powder. A direct, radiometric assay was used to follow the purification. By isoelectric focusing, the purified enzyme appeared to have an isoionic point of approx. pH 4.2, but these preparations were still not homogeneous by disc-gel electrophoresis nor by analytical ultracentrifugation. The purified enzyme has a broad pH optimum extending from pH 8.3 to 9.3 in 0.028 M phosphate/glycylglycine buffers. For optimal enzymatic activity, the ratio of magnesium to ATP must be fixed at 0.6, which suggests that for this ATP-pyrophosphoryl transfer reaction, the enzymatically preferred reactant may be Mg(ATP)6-/2. A preliminary study of the kinetics of the reaction reveals that the enzyme may function via a partial \"ping-pong\" mechanism; on this basis, dissociation constants for ATPt and for thiamine were evaluated. Pyrithiamine, butylthiamine, ethylthiamine, and oxythiamine appeared to be competitive inhibitors with respect to thiamine as the variable substrate, and their inhibitor dissociation constants were calculated. The relatively poor affinity of oxythiamine to the enzyme emphasizes the 4-amino group in the pyrimidine ring as one of the specificity requirements for thiamine pyrophosphokinase. Preliminary values for the apparent equilibrium coefficient of the thiamine pyrophosphokinase-catalyzed reaction, in terms of total species, has been approximated at several initial concentrations of reactants: e.g. K'eq,app = (see article) 9.66 - 10(-3) M; and [Th]initial - 1 - 10(-6) and 2 - 10(-6) M, respectively, where TDP, Th, t and eq represent thiamine diphosphate, thiamine, total concentration and equilibrium concentration, respectively.", "contents": "Partial purification and properties of thiamine pyrophosphokinase from pig brain. Pig brain thiamine pyrophosphokinase (ATP: thiamine pyrophosphotransferase, EC 2.7.6.2) was purified 260-fold over extracts of brain acetone powder. A direct, radiometric assay was used to follow the purification. By isoelectric focusing, the purified enzyme appeared to have an isoionic point of approx. pH 4.2, but these preparations were still not homogeneous by disc-gel electrophoresis nor by analytical ultracentrifugation. The purified enzyme has a broad pH optimum extending from pH 8.3 to 9.3 in 0.028 M phosphate/glycylglycine buffers. For optimal enzymatic activity, the ratio of magnesium to ATP must be fixed at 0.6, which suggests that for this ATP-pyrophosphoryl transfer reaction, the enzymatically preferred reactant may be Mg(ATP)6-/2. A preliminary study of the kinetics of the reaction reveals that the enzyme may function via a partial \"ping-pong\" mechanism; on this basis, dissociation constants for ATPt and for thiamine were evaluated. Pyrithiamine, butylthiamine, ethylthiamine, and oxythiamine appeared to be competitive inhibitors with respect to thiamine as the variable substrate, and their inhibitor dissociation constants were calculated. The relatively poor affinity of oxythiamine to the enzyme emphasizes the 4-amino group in the pyrimidine ring as one of the specificity requirements for thiamine pyrophosphokinase. Preliminary values for the apparent equilibrium coefficient of the thiamine pyrophosphokinase-catalyzed reaction, in terms of total species, has been approximated at several initial concentrations of reactants: e.g. K'eq,app = (see article) 9.66 - 10(-3) M; and [Th]initial - 1 - 10(-6) and 2 - 10(-6) M, respectively, where TDP, Th, t and eq represent thiamine diphosphate, thiamine, total concentration and equilibrium concentration, respectively."}
{"id": "PMID:239749", "title": "Interaction of transition metal ions with ribonuclease A. II. The selective effects of Mn2+, Zn2+, Cd2+ and Hg2+ on the histidine magnetic resonance.", "content": "Zn2+, Cd2+ and Hg2+ inhibit ribonuclease but Mn2+ does not except at very high concentrations. By high resolution NMR one can detect in the pH range 5-8 the C-2 protons of histidines 105, 12, and 119. The inhibiting ions produce large shifts of the resonance of His-12 but not of His-105. On the other hand Mn2+ broadens the C-2 proton of His-105 much more than it does those of His-12 and 119. The selective shifts suggest that the mechanism of inhibition is binding at or near the active site of which His-12 and 119 are a part. The selective broadening is a consequence of binding of the Mn2+ to a site very far from the active site but closer to His-105.", "contents": "Interaction of transition metal ions with ribonuclease A. II. The selective effects of Mn2+, Zn2+, Cd2+ and Hg2+ on the histidine magnetic resonance. Zn2+, Cd2+ and Hg2+ inhibit ribonuclease but Mn2+ does not except at very high concentrations. By high resolution NMR one can detect in the pH range 5-8 the C-2 protons of histidines 105, 12, and 119. The inhibiting ions produce large shifts of the resonance of His-12 but not of His-105. On the other hand Mn2+ broadens the C-2 proton of His-105 much more than it does those of His-12 and 119. The selective shifts suggest that the mechanism of inhibition is binding at or near the active site of which His-12 and 119 are a part. The selective broadening is a consequence of binding of the Mn2+ to a site very far from the active site but closer to His-105."}
{"id": "PMID:239750", "title": "Neurospora crassa invertase. A study of amino acids at the active center.", "content": "1. The effects on Neurospora crassa invertase (beta-D-fructofuranoside fructohydrolase, EC 3.2.1.26) of a variety of group specific reagnets and other potential inhibitors were determined during a search for an irreversible inhibitor of the enzyme. Aniline, pyridoxal, enzyme substrate and products did not inactivate invertase under reducing conditions. Bromoacetic acid, iodoacetic acid, iodoacetamide, p-chloromercuribenzoate, hydroxylamine and 2-hydroxy-5-nitrobenzyl bromide were also ineffective. Iodine was the only reagent which irreversibly inhibited invertase. 2. Invertase was rapidly inactivated by low concentrations of iodine, indicating specific inhibition. However, the enzyme could not be protected from this inactivation by substrate. It was not reactivated by mercaptoethanol or cysteine. 3. Experiments on the uptake of radioactive iodine demonstrated that invertase is not iodinated under the conditions of iodine inactivation. 4. The sedimentation (S20,w) value of invertase was not altered by iodine inactivation. One-dimensional electrophoresis and finger-printing of tryptic digests revealed no differences between iodine treated and untreated invertase. There was no loss of carbohydrate from this glycoprotein during iodine inactivation. 5. Standard amino acid analyses of iodine-inactivated invertase showed some loss of tyrosine and a trace amount of methionine sulfone. Attempts to demonstrate oxidation of methionine to the sulfone, through modification of the procedure for preparation of samples for analysis, were unsuccessful. However, oxidation of half-cystine was indicated and further loss of tyrosine noted. A hypothesis is advanced that half-cystine is oxidized by iodine to a normally unstable oxidation state which is maintained and protected by its protein invironment and that loss of tyrosine may be an artifact caused by the presence of this residue during acid hydrolysis.", "contents": "Neurospora crassa invertase. A study of amino acids at the active center. 1. The effects on Neurospora crassa invertase (beta-D-fructofuranoside fructohydrolase, EC 3.2.1.26) of a variety of group specific reagnets and other potential inhibitors were determined during a search for an irreversible inhibitor of the enzyme. Aniline, pyridoxal, enzyme substrate and products did not inactivate invertase under reducing conditions. Bromoacetic acid, iodoacetic acid, iodoacetamide, p-chloromercuribenzoate, hydroxylamine and 2-hydroxy-5-nitrobenzyl bromide were also ineffective. Iodine was the only reagent which irreversibly inhibited invertase. 2. Invertase was rapidly inactivated by low concentrations of iodine, indicating specific inhibition. However, the enzyme could not be protected from this inactivation by substrate. It was not reactivated by mercaptoethanol or cysteine. 3. Experiments on the uptake of radioactive iodine demonstrated that invertase is not iodinated under the conditions of iodine inactivation. 4. The sedimentation (S20,w) value of invertase was not altered by iodine inactivation. One-dimensional electrophoresis and finger-printing of tryptic digests revealed no differences between iodine treated and untreated invertase. There was no loss of carbohydrate from this glycoprotein during iodine inactivation. 5. Standard amino acid analyses of iodine-inactivated invertase showed some loss of tyrosine and a trace amount of methionine sulfone. Attempts to demonstrate oxidation of methionine to the sulfone, through modification of the procedure for preparation of samples for analysis, were unsuccessful. However, oxidation of half-cystine was indicated and further loss of tyrosine noted. A hypothesis is advanced that half-cystine is oxidized by iodine to a normally unstable oxidation state which is maintained and protected by its protein invironment and that loss of tyrosine may be an artifact caused by the presence of this residue during acid hydrolysis."}
{"id": "PMID:239751", "title": "Action of crystalline acid carboxypeptidase from Penicillium janthinellum.", "content": "Acid carboxypeptidase (EC 3.4.12.-) crystallized from culture filtrate of Penicillium janthinellum has been investigated for its use in carboxy-terminal sequence determination of Z-Gly-Pro-Leu-Gly, Z-Gly-Pro-Leu-Gly-Pro, angiotensin I, native lysozyme, native ribonuclease T1, and reduced S-carboxy-methyl-lysozyme. The examination indicated that proline and glycine were liberated from Z-Gly-Pro-Leu-Gly-Pro. At high enzyme concentration, the enzyme catalyzed complete sequential release of amino acids from the carboxy-terminal leucine to the amino-terminal aspartic acid of angiotensin I. The enzyme released the carboxy-terminal leucine from native lysozyme, however, no release of the threonine from native ribonuclease T1 was observed after a prolonged period of incubation with the enzyme. The sequence of the first nine carboxy-terminal residues of denatured lysozyme, leucine, arginine, S-carboxymethyl-cysteine, glycine, arginine, isoleucine, tryptophane, alanine, and glutamine, could be deduced unequivocally from a time release plot of an incubation mixture with the enzyme.", "contents": "Action of crystalline acid carboxypeptidase from Penicillium janthinellum. Acid carboxypeptidase (EC 3.4.12.-) crystallized from culture filtrate of Penicillium janthinellum has been investigated for its use in carboxy-terminal sequence determination of Z-Gly-Pro-Leu-Gly, Z-Gly-Pro-Leu-Gly-Pro, angiotensin I, native lysozyme, native ribonuclease T1, and reduced S-carboxy-methyl-lysozyme. The examination indicated that proline and glycine were liberated from Z-Gly-Pro-Leu-Gly-Pro. At high enzyme concentration, the enzyme catalyzed complete sequential release of amino acids from the carboxy-terminal leucine to the amino-terminal aspartic acid of angiotensin I. The enzyme released the carboxy-terminal leucine from native lysozyme, however, no release of the threonine from native ribonuclease T1 was observed after a prolonged period of incubation with the enzyme. The sequence of the first nine carboxy-terminal residues of denatured lysozyme, leucine, arginine, S-carboxymethyl-cysteine, glycine, arginine, isoleucine, tryptophane, alanine, and glutamine, could be deduced unequivocally from a time release plot of an incubation mixture with the enzyme."}
{"id": "PMID:239752", "title": "Purification of granulocyte neutral protease from human blood and rheumatoid synovial fluid.", "content": "The neutral protease activity of human synovial fluid cells, like that of peripheral blood leucocytes, is located in a granule fraction. It can be solubilised by various agents but only 1 M neutral salts do so without inactivation. Salt-solubilised neutral protease has been purified (300 X) from synovial fluid cells; like preparations obtained in the same way (600 X purified) from peripheral blood leucocytes, it has a broad pH profile of activity (pH 7--10.5) and in this, as well as in substrate specificity and sensitivity to activators and inhibitors, it behaves as a serine-histidine type protease similar to elastase (EC 3.4.21.11). The product showed two major components on polyacrylamide gel electrophoresis. Collagenase or chymotrypsin-like activity were not detected.", "contents": "Purification of granulocyte neutral protease from human blood and rheumatoid synovial fluid. The neutral protease activity of human synovial fluid cells, like that of peripheral blood leucocytes, is located in a granule fraction. It can be solubilised by various agents but only 1 M neutral salts do so without inactivation. Salt-solubilised neutral protease has been purified (300 X) from synovial fluid cells; like preparations obtained in the same way (600 X purified) from peripheral blood leucocytes, it has a broad pH profile of activity (pH 7--10.5) and in this, as well as in substrate specificity and sensitivity to activators and inhibitors, it behaves as a serine-histidine type protease similar to elastase (EC 3.4.21.11). The product showed two major components on polyacrylamide gel electrophoresis. Collagenase or chymotrypsin-like activity were not detected."}
{"id": "PMID:239753", "title": "pH effects in plasmin-catalysed hydrolysis of alpha-N-benzoyl-L-arginine compounds.", "content": "The steady-state kinetics of plasmin (EC 3.4.21.7) catalysed reactions with some alpha-N-benzoyl-L-arginine compounds is investigated in the pH range 5.8--9.0. The results are interpreted in terms of a three-step mechanism, which involves enzyme-substrate complex formation, followed by acylation and deacylation of the enzyme. Alpha-N-Benzoyl-L-arginine methyl ester and ethyl ester show the same pH behaviour. The kinetic parameter kc/Km is influenced by two groups with pK values of 6.5 and 8.4, respectively. kc is affected only by the group with pK equal to 6.5 and Km only by the group with pK equal to 8.4. It is suggested that the group with pK equal to 6.5 is the 1-chloro-3-tosyl-amido-7-amino-2-heptanone-sensitive histidine residue in the active site and that the group with pK equal to 8.4 is perhaps the alpha-amino group of the N-terminus in analogy to trypsin and chymotrypsin. alpha-N-Benzoyl-L-arginine amide is not hydrolysed by plasmin, but proves to be a competitive inhibitor, Ki = 12.8 +/- 1.8 mM, pH = 7.8. Also the product alpha-N-benzoyl-L-arginine is a competitive inhibitor, Ki = 26 +/- 3.1 mM, pH = 7.8. Estimates of individual rate constants are compared with similar trypsin data.", "contents": "pH effects in plasmin-catalysed hydrolysis of alpha-N-benzoyl-L-arginine compounds. The steady-state kinetics of plasmin (EC 3.4.21.7) catalysed reactions with some alpha-N-benzoyl-L-arginine compounds is investigated in the pH range 5.8--9.0. The results are interpreted in terms of a three-step mechanism, which involves enzyme-substrate complex formation, followed by acylation and deacylation of the enzyme. Alpha-N-Benzoyl-L-arginine methyl ester and ethyl ester show the same pH behaviour. The kinetic parameter kc/Km is influenced by two groups with pK values of 6.5 and 8.4, respectively. kc is affected only by the group with pK equal to 6.5 and Km only by the group with pK equal to 8.4. It is suggested that the group with pK equal to 6.5 is the 1-chloro-3-tosyl-amido-7-amino-2-heptanone-sensitive histidine residue in the active site and that the group with pK equal to 8.4 is perhaps the alpha-amino group of the N-terminus in analogy to trypsin and chymotrypsin. alpha-N-Benzoyl-L-arginine amide is not hydrolysed by plasmin, but proves to be a competitive inhibitor, Ki = 12.8 +/- 1.8 mM, pH = 7.8. Also the product alpha-N-benzoyl-L-arginine is a competitive inhibitor, Ki = 26 +/- 3.1 mM, pH = 7.8. Estimates of individual rate constants are compared with similar trypsin data."}
{"id": "PMID:239754", "title": "pH gradient across the lysosomal membrane generated by selective cation permeability and Donnan equilibrium.", "content": "The pH within isolated Triton WR 1339-filled rat liver lysosomes was determined by measuring the distribution of [14C]methylamine between the intra- and extralysosomal space. The intralysosomal pH was found to be approximately one pH unit lower than that of the surrounding medium. Increasing the extralysosomal cation concentration lowered the pH gradient by a cation exchange indicating the presence of a Donnan equilibrium. The lysosomal membrane was found to be significantly more permeable to protons than to other cations. The relative mobility of cations through the lysosomal membrane is H+ greater than Cs+ greater than Rb+ greater than K greater than Na+ greater than Li+ greater than Mg2+, Ca2+. The presented data suggest that the acidity within isolated Triton WR 1339-filled lysosomes is maintained by: (1) a Donnan equilibrium resulting from the intralysosomal accumulation of nondiffusible anions and (2) a selective permeability of the lysosomal membrane to cations.", "contents": "pH gradient across the lysosomal membrane generated by selective cation permeability and Donnan equilibrium. The pH within isolated Triton WR 1339-filled rat liver lysosomes was determined by measuring the distribution of [14C]methylamine between the intra- and extralysosomal space. The intralysosomal pH was found to be approximately one pH unit lower than that of the surrounding medium. Increasing the extralysosomal cation concentration lowered the pH gradient by a cation exchange indicating the presence of a Donnan equilibrium. The lysosomal membrane was found to be significantly more permeable to protons than to other cations. The relative mobility of cations through the lysosomal membrane is H+ greater than Cs+ greater than Rb+ greater than K greater than Na+ greater than Li+ greater than Mg2+, Ca2+. The presented data suggest that the acidity within isolated Triton WR 1339-filled lysosomes is maintained by: (1) a Donnan equilibrium resulting from the intralysosomal accumulation of nondiffusible anions and (2) a selective permeability of the lysosomal membrane to cations."}
{"id": "PMID:239755", "title": "The binding of fd gene-5 protein to single-stranded nucleic acid.", "content": "The gene-5 protein of the fd filamentous bacterial virus binds to single-stranded DNA over a pH range of 2-10.3. Binding to fd DNA is several hundred-fold stronger than to bacteriophage R17 RNA or to DNA tetranucleotides.", "contents": "The binding of fd gene-5 protein to single-stranded nucleic acid. The gene-5 protein of the fd filamentous bacterial virus binds to single-stranded DNA over a pH range of 2-10.3. Binding to fd DNA is several hundred-fold stronger than to bacteriophage R17 RNA or to DNA tetranucleotides."}
{"id": "PMID:239756", "title": "Quantitative separation of nucleotides on mercurated dextran.", "content": "Dextran gels of varying porosites (Sephadex G series) were chemically modified so as to contain covalently bound monofunctional mercury. Mercurated Sephadex of the porosity G-25 was then used to fractionate mixtures of mono- and dinucleotides into the constituent components. Separation is based on the affinity of the nitrogen binding sites of the purine and pyrimidine derivatives for organomercurial Hg+. Thus, a mixture composed of the four mononucleotides Cyd-5'-P, Ado-3'-P, Guo-2'(3')-P, dThd-5'-P and of the four dinucleotides Cyd-P-Cyd, Ado-P-Ado, Guo-P-Urd, and Urd-P-Urd could be separated into eight well-resolved fractions by using a combination Tris-bicarbonate/carbonate buffer system of increasing pH as an eluent. Complete separation was also achieved when a mixture of Ado 3:5'-P, Ado 5'-P, Ado-5'-PP, and Ado-5'-PPP was fractionated on mercurated Sephadex G-25. Again, Tris-bicarbonate/carbonate buffer served as an eluent. Lastly, fractionation can also be performed at a constant pH by offering other suitable ligands, for instance Cl-, that will compete with nucleotides for monofunctional Hg+. The fractionation behavior of mercurated Sephadex G-25 can be fully understood on the basis of the complexing properties of monofunctional Hg+. This has been shown by calculating the net retention volume ratios of several nucleotides with the help of the known interaction parameters of corresponding nucleosides with CH3 HgOH and by comparing the predicted ratios with the experimentally measured ones. Finally, the acid-base properties of mercurated Sephadex G-25 as well as its affinity for chloride and iodide ions have been determined. The data agree quite well with those known for CH3 HgOH.", "contents": "Quantitative separation of nucleotides on mercurated dextran. Dextran gels of varying porosites (Sephadex G series) were chemically modified so as to contain covalently bound monofunctional mercury. Mercurated Sephadex of the porosity G-25 was then used to fractionate mixtures of mono- and dinucleotides into the constituent components. Separation is based on the affinity of the nitrogen binding sites of the purine and pyrimidine derivatives for organomercurial Hg+. Thus, a mixture composed of the four mononucleotides Cyd-5'-P, Ado-3'-P, Guo-2'(3')-P, dThd-5'-P and of the four dinucleotides Cyd-P-Cyd, Ado-P-Ado, Guo-P-Urd, and Urd-P-Urd could be separated into eight well-resolved fractions by using a combination Tris-bicarbonate/carbonate buffer system of increasing pH as an eluent. Complete separation was also achieved when a mixture of Ado 3:5'-P, Ado 5'-P, Ado-5'-PP, and Ado-5'-PPP was fractionated on mercurated Sephadex G-25. Again, Tris-bicarbonate/carbonate buffer served as an eluent. Lastly, fractionation can also be performed at a constant pH by offering other suitable ligands, for instance Cl-, that will compete with nucleotides for monofunctional Hg+. The fractionation behavior of mercurated Sephadex G-25 can be fully understood on the basis of the complexing properties of monofunctional Hg+. This has been shown by calculating the net retention volume ratios of several nucleotides with the help of the known interaction parameters of corresponding nucleosides with CH3 HgOH and by comparing the predicted ratios with the experimentally measured ones. Finally, the acid-base properties of mercurated Sephadex G-25 as well as its affinity for chloride and iodide ions have been determined. The data agree quite well with those known for CH3 HgOH."}
{"id": "PMID:239762", "title": "Cardiac output measurement with a simplified thermodilution technique. Comparison with the Fick method.", "content": "A simplified thermodilution technique for cardiac output measurement is compared with the Fick method in dogs, over a wide range of cardiac output values. The reproducibility of the method is satisfactory (differences less than 10 per cent for 95 per cent of the measurements). The overall correlation factor (r = 0.97) is highly significant for cardiac outputs ranging from 750 to 7,500 ml.mn(-1). The influence of hematocrit (when lower than 30%) and of the injection site of indicator are discussed. Present experiments confirm that the use of pre-set factors allow for the thermal loss inside the catheter does not obviate the accuracy of thermodilution method for cardiac output measurements. The slope of the regression line is very close to 1. Lack of fit to linearity is tested and is found not significant throughout the explored range. This technique should therefore have extensive clinical applications.", "contents": "Cardiac output measurement with a simplified thermodilution technique. Comparison with the Fick method. A simplified thermodilution technique for cardiac output measurement is compared with the Fick method in dogs, over a wide range of cardiac output values. The reproducibility of the method is satisfactory (differences less than 10 per cent for 95 per cent of the measurements). The overall correlation factor (r = 0.97) is highly significant for cardiac outputs ranging from 750 to 7,500 ml.mn(-1). The influence of hematocrit (when lower than 30%) and of the injection site of indicator are discussed. Present experiments confirm that the use of pre-set factors allow for the thermal loss inside the catheter does not obviate the accuracy of thermodilution method for cardiac output measurements. The slope of the regression line is very close to 1. Lack of fit to linearity is tested and is found not significant throughout the explored range. This technique should therefore have extensive clinical applications."}
{"id": "PMID:239774", "title": "Nonlinear regression methods in design of experiments and mathematical modelling. Applications to the analysis of the steady-state kinetics of glutathione reductase.", "content": "A branching reaction pathway involving a ping pong and a sequential loop has been proposed for glutathione reductase (Biochem. Biophys. Res. Commun. 53 (1973) 1151). In the present investigation nonlinear regression methods have been applied in the fitting of rate equations to experimental data to test the validity of the model proposed and to discriminate between alternative mathematical models (cf. FEBS Lett. 26 (1972) 252). In the best rate law, some of the parameters were numerically redundant. Therefore, a feature-wise analysis of the rate equation was carried out by varying one substrate concentration at a time. The overall strategy used was a cyclic procedure involving: experimentation - analysis of data - modelling - design of experiments - new experimentation etc. Consideration was given to the experimental error structure and to the importance of weighting in the regression analysis. In the design of experiments for discrimination between rival models, a previously defined discrimination function was used. The results of the analysis support the branching reaction scheme proposed for glutathione reductase.", "contents": "Nonlinear regression methods in design of experiments and mathematical modelling. Applications to the analysis of the steady-state kinetics of glutathione reductase. A branching reaction pathway involving a ping pong and a sequential loop has been proposed for glutathione reductase (Biochem. Biophys. Res. Commun. 53 (1973) 1151). In the present investigation nonlinear regression methods have been applied in the fitting of rate equations to experimental data to test the validity of the model proposed and to discriminate between alternative mathematical models (cf. FEBS Lett. 26 (1972) 252). In the best rate law, some of the parameters were numerically redundant. Therefore, a feature-wise analysis of the rate equation was carried out by varying one substrate concentration at a time. The overall strategy used was a cyclic procedure involving: experimentation - analysis of data - modelling - design of experiments - new experimentation etc. Consideration was given to the experimental error structure and to the importance of weighting in the regression analysis. In the design of experiments for discrimination between rival models, a previously defined discrimination function was used. The results of the analysis support the branching reaction scheme proposed for glutathione reductase."}
{"id": "PMID:239775", "title": "Energetics of abiogenic chemical systems.", "content": "After recalling the energy consumption necessary to produce the main categories of biochemicals from the equilibrium state of an hydrogenated atmosphere, the primary processes by which energy can be absorbed in a mixture of methane and ammonia in the presence of aqueous solutions are defined. From the very first excitations, unsaturated products are formed. In fact, this formation of atmospheric precursors is the primordial state of a photochemically induced redox dismutation. The evolution of solutions obtained from the dissolution of these atmospheric precursors in aqueous media is described from experimental data and analysed on energetic grounds. The relaxation of energy accumulated in such solutions involves non enzymic archetypes of the main categories of metabolic processes; in particular some unsaturated atmospheric precursors must be looked upon as primordial representatives of biochemical dehydrating agents. Absorption of light energy in the solutions obtained from the evolution of precursors happens near the visible range and should govern their further evolution. In fact, biochemicals which were previously detected as products of model experiments are not present in these solutions. They were probably obtained during analytical procedures from products of the evolution of atmospheric precursors which are unstable against decreases of pH. Cyclic autocatalytic effects must be involved in the further evolution of the models of the first aqueous solutions. Their possible role in the appearance of optical dissymmetry is emphasized on theoretical grounds.", "contents": "Energetics of abiogenic chemical systems. After recalling the energy consumption necessary to produce the main categories of biochemicals from the equilibrium state of an hydrogenated atmosphere, the primary processes by which energy can be absorbed in a mixture of methane and ammonia in the presence of aqueous solutions are defined. From the very first excitations, unsaturated products are formed. In fact, this formation of atmospheric precursors is the primordial state of a photochemically induced redox dismutation. The evolution of solutions obtained from the dissolution of these atmospheric precursors in aqueous media is described from experimental data and analysed on energetic grounds. The relaxation of energy accumulated in such solutions involves non enzymic archetypes of the main categories of metabolic processes; in particular some unsaturated atmospheric precursors must be looked upon as primordial representatives of biochemical dehydrating agents. Absorption of light energy in the solutions obtained from the evolution of precursors happens near the visible range and should govern their further evolution. In fact, biochemicals which were previously detected as products of model experiments are not present in these solutions. They were probably obtained during analytical procedures from products of the evolution of atmospheric precursors which are unstable against decreases of pH. Cyclic autocatalytic effects must be involved in the further evolution of the models of the first aqueous solutions. Their possible role in the appearance of optical dissymmetry is emphasized on theoretical grounds."}
{"id": "PMID:239777", "title": "Endogenous oscillations in pathways of energy transduction as related to circadian rhythmicity and photoperiodic control.", "content": "Evidence is presented for endogenous rhythmicity in energy transducing sequences of cellular metabolism which result in a circadian rhythm in adenylate \"energy charge\" and redox state (NADPH/NADP). From phase dependent photocontrol of enzymatic activity and pyridine nucleotide pool-size levels it is concluded that light - via photoreceptor(s) of photoperiodic control - modulates energy flow under conditions where overall energy transduction displays a circadian rhythm. The results are discussed in relation to temporal organization of development in general.", "contents": "Endogenous oscillations in pathways of energy transduction as related to circadian rhythmicity and photoperiodic control. Evidence is presented for endogenous rhythmicity in energy transducing sequences of cellular metabolism which result in a circadian rhythm in adenylate \"energy charge\" and redox state (NADPH/NADP). From phase dependent photocontrol of enzymatic activity and pyridine nucleotide pool-size levels it is concluded that light - via photoreceptor(s) of photoperiodic control - modulates energy flow under conditions where overall energy transduction displays a circadian rhythm. The results are discussed in relation to temporal organization of development in general."}
{"id": "PMID:239781", "title": "Influence on clinical practice of routine intra-partum fetal monitoring.", "content": "An attempt has been made to monitor by continuous fetal heart rate according all women admitted in labour. Altogether 85% of the 1070 patients delivered at one hospital were monitored in 1973 and 92% in 1974. Perinatal mortality fell significantly from levels in preceding years to 15-8 and 11-7 per 1000 births, respectively, in 1973 and 1974. The fall was primarily due to the elimination of intra-partum stillbirths and a significant reduction in neonatal mortality. The incidence of caesarean sections also fell from 9-7% in 1973 to 5-8% in 1974. All patients should be monitored because it is impossible to predict reliably intra-partum fetal distress from maternal \"high-risk\" factors present before the onset of labour.", "contents": "Influence on clinical practice of routine intra-partum fetal monitoring. An attempt has been made to monitor by continuous fetal heart rate according all women admitted in labour. Altogether 85% of the 1070 patients delivered at one hospital were monitored in 1973 and 92% in 1974. Perinatal mortality fell significantly from levels in preceding years to 15-8 and 11-7 per 1000 births, respectively, in 1973 and 1974. The fall was primarily due to the elimination of intra-partum stillbirths and a significant reduction in neonatal mortality. The incidence of caesarean sections also fell from 9-7% in 1973 to 5-8% in 1974. All patients should be monitored because it is impossible to predict reliably intra-partum fetal distress from maternal \"high-risk\" factors present before the onset of labour."}
{"id": "PMID:239782", "title": "Diagnosis of dyspepsia from data collected by a physician's assistant.", "content": "This paper presents a study of the diagnosis of \"dyspepsia\" in 154 patients based on data collected at their initial outpatient attendance via an interview with a non-medically qualified physician's assistant. The reactions of patients to this type of interview were favourable, and the data recorded were as reliable as those recorded by clinicians. We conclude (1) that the data recorded by the physician's assistant are valuable diagnostically; (2) where these cannot be collected by a qualified physician, this task may be delegated to a non-medically qualified person; but (3) this interview should augment and not replace the traditional clinical interview.", "contents": "Diagnosis of dyspepsia from data collected by a physician's assistant. This paper presents a study of the diagnosis of \"dyspepsia\" in 154 patients based on data collected at their initial outpatient attendance via an interview with a non-medically qualified physician's assistant. The reactions of patients to this type of interview were favourable, and the data recorded were as reliable as those recorded by clinicians. We conclude (1) that the data recorded by the physician's assistant are valuable diagnostically; (2) where these cannot be collected by a qualified physician, this task may be delegated to a non-medically qualified person; but (3) this interview should augment and not replace the traditional clinical interview."}
{"id": "PMID:239780", "title": "[Hemoglobin oxygen transport during experimental acute hypercapnia (author's transl)].", "content": "The effects on hemoglobin oxygen transport of acute respiratory acidosis have been studied in dogs inhaling a gaseous mixture with 12% CO2 (O2 21%) for two to five hours. In a first series of experiments, it was shown that the shape of the oxyhemoglobin dissociation curve (ODC) was not modified by severe acidosis (pH congruent to 7) lasting for two and a half hours. The Hill number (N equals 2.6) did not change significantly. The aim of the second experimental series was to stuey the Bohr effect and the hemoglobin oxygen affinity (P50). The control value for the respiratory Bohr coefficient (B) was --0.54; neither after two hours (--0.52), nor after five hours of hypercapnia (--0.55) was it significantly modified. The P50 expressed at arterial pH was much increased in acidosis (congruent to 45 torr); when expressed at standard p/ 7.4, it was slightly but significantly decreased (congruent to 1 torr) at the fifth hour. At the same time there was a decrease (p smaller than 0.05) in the erythrocyte 2,3-DPG approaching 15 p. cent; on the other hand the ATP concentration did not change significantly. No significant individual correlation was found between P50(7.4), 2,3-DPG and mean hemoglobin corpuscular concentration. These results suggest that during severe respiratory acidosis neither a change in the shape of ODC, nor a change in Bohr effect do affect the hemoglobin oxygen transport. The main characteristic remains the decrease in oxygen affinity of hemoglobin, due to the erythrocyte [H+] increase induced by hypercapnia ; this phenomenon is observed as long as the 2,3-DPG decrease stays moderate.", "contents": "[Hemoglobin oxygen transport during experimental acute hypercapnia (author's transl)]. The effects on hemoglobin oxygen transport of acute respiratory acidosis have been studied in dogs inhaling a gaseous mixture with 12% CO2 (O2 21%) for two to five hours. In a first series of experiments, it was shown that the shape of the oxyhemoglobin dissociation curve (ODC) was not modified by severe acidosis (pH congruent to 7) lasting for two and a half hours. The Hill number (N equals 2.6) did not change significantly. The aim of the second experimental series was to stuey the Bohr effect and the hemoglobin oxygen affinity (P50). The control value for the respiratory Bohr coefficient (B) was --0.54; neither after two hours (--0.52), nor after five hours of hypercapnia (--0.55) was it significantly modified. The P50 expressed at arterial pH was much increased in acidosis (congruent to 45 torr); when expressed at standard p/ 7.4, it was slightly but significantly decreased (congruent to 1 torr) at the fifth hour. At the same time there was a decrease (p smaller than 0.05) in the erythrocyte 2,3-DPG approaching 15 p. cent; on the other hand the ATP concentration did not change significantly. No significant individual correlation was found between P50(7.4), 2,3-DPG and mean hemoglobin corpuscular concentration. These results suggest that during severe respiratory acidosis neither a change in the shape of ODC, nor a change in Bohr effect do affect the hemoglobin oxygen transport. The main characteristic remains the decrease in oxygen affinity of hemoglobin, due to the erythrocyte [H+] increase induced by hypercapnia ; this phenomenon is observed as long as the 2,3-DPG decrease stays moderate."}
{"id": "PMID:239784", "title": "Stereospecific binding of D-lysergic acid diethylamide (LSD) to brain membranes: relationship to serotonin receptors.", "content": "D-[3H]LSD binds saturably, reversibly, and with a high affinity (KD = 10 nM) to rat brain membranes. The association and dissociation rates of binding are temperature dependent and fastest at 37 degrees C. Binding is enriched in crude microsomal (P3) membranes. D-[3H]LSD binding is stereospecific as L-LSD, the psychotropically inactive enatiomer, is 1000 times weaker than D-LSD as a displacing agent. The potencies of other LSD analogues parallel their psychotropic activity with the exception of 2-bromo-LSD (psychotropically inactive) which is as potent as D-LSD in displacing bound D-[3H]LSD. Serotonin is the only putative neurotransmitter with affinity (ED50 = 3 muM) for the LSD binding site, and psychotropically active alkylindoleamines are also potent displacing agents. Destruction of presynaptic serotonin neuronal elements by lesioning the midbrain raphe nuclei does not chang the affinity or maximum number of detectable in vitro D-[3H]LSD bindind sites. The regional distribution in monkey brain of D-[3H]LSD binding and high affinity [3h]serotonin uptake, a marker for pre-synaptic serotonin nerve terminal density, shows some correlation. The most notable exceptions are cerebral cortical areas which are highest in D-[3H]LSD binding and only intermediate in [3h]serotonin uptake. Our evidence suggests that D-[3H]LSD binds to post-synaptic serotonin receptors.", "contents": "Stereospecific binding of D-lysergic acid diethylamide (LSD) to brain membranes: relationship to serotonin receptors. D-[3H]LSD binds saturably, reversibly, and with a high affinity (KD = 10 nM) to rat brain membranes. The association and dissociation rates of binding are temperature dependent and fastest at 37 degrees C. Binding is enriched in crude microsomal (P3) membranes. D-[3H]LSD binding is stereospecific as L-LSD, the psychotropically inactive enatiomer, is 1000 times weaker than D-LSD as a displacing agent. The potencies of other LSD analogues parallel their psychotropic activity with the exception of 2-bromo-LSD (psychotropically inactive) which is as potent as D-LSD in displacing bound D-[3H]LSD. Serotonin is the only putative neurotransmitter with affinity (ED50 = 3 muM) for the LSD binding site, and psychotropically active alkylindoleamines are also potent displacing agents. Destruction of presynaptic serotonin neuronal elements by lesioning the midbrain raphe nuclei does not chang the affinity or maximum number of detectable in vitro D-[3H]LSD bindind sites. The regional distribution in monkey brain of D-[3H]LSD binding and high affinity [3h]serotonin uptake, a marker for pre-synaptic serotonin nerve terminal density, shows some correlation. The most notable exceptions are cerebral cortical areas which are highest in D-[3H]LSD binding and only intermediate in [3h]serotonin uptake. Our evidence suggests that D-[3H]LSD binds to post-synaptic serotonin receptors."}
{"id": "PMID:239786", "title": "Studies of suspected neurotransmitters in the vestibuloocular pathways.", "content": "Isolated fresh cat trochlear and oculomotor nuclei, which contain the axon terminals of inhibitory neurons whose cell bodies are in the superior vestibular nucleus (SVN), actively synthesize and store [3H]GABA, [14C]acetylcholine, [3H]dopamine and [3H]tyramine from labeled precursors of these compounds. Twelve to 14 days following lesions of the ipsilateral superior vestibular nucleus or its efferent pathway to the oculomotor and trochlear nuclei, at a time when there is extensive degeneration of superior vestibular nucleus axon terminals in these nuclei, the synthesis and storage of GABA in the ipsilateral trochlear nucleus is markedly reduced compared to that in the contralateral trochlear nucleus; the synthesis of acetylcholine, dopamine and tyramine is not measurably affected. The oculomotor nuclei, which unlike the trochlear nuclei receive a heavy bilateral projection from the SVN, show no asymmetric decrease after SVN lesions in their ability to synthesize any of the compounds tested. The data support the identity of GABA as an inhibitory transmitter in the superior vestibular nucleus-trochlear nucleus pathway.", "contents": "Studies of suspected neurotransmitters in the vestibuloocular pathways. Isolated fresh cat trochlear and oculomotor nuclei, which contain the axon terminals of inhibitory neurons whose cell bodies are in the superior vestibular nucleus (SVN), actively synthesize and store [3H]GABA, [14C]acetylcholine, [3H]dopamine and [3H]tyramine from labeled precursors of these compounds. Twelve to 14 days following lesions of the ipsilateral superior vestibular nucleus or its efferent pathway to the oculomotor and trochlear nuclei, at a time when there is extensive degeneration of superior vestibular nucleus axon terminals in these nuclei, the synthesis and storage of GABA in the ipsilateral trochlear nucleus is markedly reduced compared to that in the contralateral trochlear nucleus; the synthesis of acetylcholine, dopamine and tyramine is not measurably affected. The oculomotor nuclei, which unlike the trochlear nuclei receive a heavy bilateral projection from the SVN, show no asymmetric decrease after SVN lesions in their ability to synthesize any of the compounds tested. The data support the identity of GABA as an inhibitory transmitter in the superior vestibular nucleus-trochlear nucleus pathway."}
{"id": "PMID:239787", "title": "Precipitation of calcium phosphates from electrolyte solutions.  III. Radiometric studies of the kinetics of precipitation and aging of calcium phosphates.", "content": "Precipitation and precipitate transformation in the system sodium phosphate (pre-adjusted to pH 7.4)--calcium chloride (25 degrees) was studied by means of radiometric analysis using 45Ca and 32P as tracers.  Changes in the pH and the total concentrations of calcium and phosphate were followed during solid phase formation and the data were used to calculate composition changes of the precipitates and their supernatants.  In all investigated systems two-step precipitation was observed, the precursor being more basic than the secondary precipitate.  The composition of the latter was mostly within the range of the composition of octacalcium phosphate.  The course of further chemical changes was dependent on the pH established during secondary precipitation.  The heterogeneous exchange of the radionuclides between the solid phase and their supernatant solutions was also followed as a function of time.  The results indicate that recrystallization through the mother liquid accompanied by composition changes is the dominant mechanism of equilibrium of the solid phases.", "contents": "Precipitation of calcium phosphates from electrolyte solutions.  III. Radiometric studies of the kinetics of precipitation and aging of calcium phosphates. Precipitation and precipitate transformation in the system sodium phosphate (pre-adjusted to pH 7.4)--calcium chloride (25 degrees) was studied by means of radiometric analysis using 45Ca and 32P as tracers.  Changes in the pH and the total concentrations of calcium and phosphate were followed during solid phase formation and the data were used to calculate composition changes of the precipitates and their supernatants.  In all investigated systems two-step precipitation was observed, the precursor being more basic than the secondary precipitate.  The composition of the latter was mostly within the range of the composition of octacalcium phosphate.  The course of further chemical changes was dependent on the pH established during secondary precipitation.  The heterogeneous exchange of the radionuclides between the solid phase and their supernatant solutions was also followed as a function of time.  The results indicate that recrystallization through the mother liquid accompanied by composition changes is the dominant mechanism of equilibrium of the solid phases."}
{"id": "PMID:239788", "title": "Studies on tyrosine hydroxylase in neuroblastoma in relation to urinary levels of catecholamine metabolites.", "content": "Tyrosine hydroxylase (TH) activity has been determined in 22 neuroblastoma tumors from 15 patients, in 1 pheochromocytoma, 20 adrenal glands, 10 other tumors and organs, and 4 specimens of sera. The enzyme activity was found only in the neural crest tumors and adrenal glands, but the levels were too low to be detected in the other tumors and in normal liver and kidney tissues. The average specific activity (mean +/- SE) of TH in 23 neural crest tumors was 0.559 +/- 0.101; in 20 adrenal glands was 0.418 +/- 0.124 nmol/mg protein/minute. In 13 patients with neuroblastoma and 1 patient with pheochromocytoma, both TH levels in the primary tumors and urinary excretion of vanillylmandelic acid (VMA) and homovanillic acid (HVA) were studied. The urinary excretion of VMA by 10 of 13 neuroblastoma patients and by the patient with pheochromocytoma was significantly to markedly elevated above normal levels; excretion of HVA by 12 of 13 neuroblastoma patients was similarly elevated. These results indicate that tyrosine hydroxylase, an enzyme specifically located in the adrenal medulla and monoaminergic neurons, is also present in neuroblastoma, a malignant tumor of similar embryologic origin, and in pheochromocytoma. Not only can TH activity in these tumors be demonstrated in vitro, but the elevated urinary excretion of VMA and/or HVA by the majority of patients with these tumors also indicates TH activity of the tumors in vivo.", "contents": "Studies on tyrosine hydroxylase in neuroblastoma in relation to urinary levels of catecholamine metabolites. Tyrosine hydroxylase (TH) activity has been determined in 22 neuroblastoma tumors from 15 patients, in 1 pheochromocytoma, 20 adrenal glands, 10 other tumors and organs, and 4 specimens of sera. The enzyme activity was found only in the neural crest tumors and adrenal glands, but the levels were too low to be detected in the other tumors and in normal liver and kidney tissues. The average specific activity (mean +/- SE) of TH in 23 neural crest tumors was 0.559 +/- 0.101; in 20 adrenal glands was 0.418 +/- 0.124 nmol/mg protein/minute. In 13 patients with neuroblastoma and 1 patient with pheochromocytoma, both TH levels in the primary tumors and urinary excretion of vanillylmandelic acid (VMA) and homovanillic acid (HVA) were studied. The urinary excretion of VMA by 10 of 13 neuroblastoma patients and by the patient with pheochromocytoma was significantly to markedly elevated above normal levels; excretion of HVA by 12 of 13 neuroblastoma patients was similarly elevated. These results indicate that tyrosine hydroxylase, an enzyme specifically located in the adrenal medulla and monoaminergic neurons, is also present in neuroblastoma, a malignant tumor of similar embryologic origin, and in pheochromocytoma. Not only can TH activity in these tumors be demonstrated in vitro, but the elevated urinary excretion of VMA and/or HVA by the majority of patients with these tumors also indicates TH activity of the tumors in vivo."}
{"id": "PMID:239795", "title": "[The polyphosphate synthetase of Saccharomyces cerevisiae].", "content": "The polyphosphate-synthetase, isolated from a homogenate of phosphate starved cells, catalyses the synthesis of linear polyphosphates from orthophosphate. It is localized in the membrane fraction which deposits between 400 and 1000 X g; its optimal pH is 7.1; its KM toward orthophosphate is 4.0 X 10(-4) M; ATP stimulates the reaction. The enzyme synthezises especially polyphosphates with short chain length.", "contents": "[The polyphosphate synthetase of Saccharomyces cerevisiae]. The polyphosphate-synthetase, isolated from a homogenate of phosphate starved cells, catalyses the synthesis of linear polyphosphates from orthophosphate. It is localized in the membrane fraction which deposits between 400 and 1000 X g; its optimal pH is 7.1; its KM toward orthophosphate is 4.0 X 10(-4) M; ATP stimulates the reaction. The enzyme synthezises especially polyphosphates with short chain length."}
{"id": "PMID:239796", "title": "[Effect of hypercapnia on the acid base states of the blood in the crab Carcinus maenas (L.) (Crustacea-Decapoda)].", "content": "When the crab Carcinus maenas respires in hypercapnic water, a respiratory acidosis occurs, which is progressively compensated by a rise of the blood bicarbonate concentration. The CO2 partial pressure in the blood increases in proportion to the change in ambient CO2 partial pressure. Therefore, the regulation of the acid-base status depends mainly on non-respiratory adjustments of the blood bicarbonate concentrations.", "contents": "[Effect of hypercapnia on the acid base states of the blood in the crab Carcinus maenas (L.) (Crustacea-Decapoda)]. When the crab Carcinus maenas respires in hypercapnic water, a respiratory acidosis occurs, which is progressively compensated by a rise of the blood bicarbonate concentration. The CO2 partial pressure in the blood increases in proportion to the change in ambient CO2 partial pressure. Therefore, the regulation of the acid-base status depends mainly on non-respiratory adjustments of the blood bicarbonate concentrations."}
{"id": "PMID:239797", "title": "[The effect of irradiation conditions on the radioinduced acidity of solid phase glucose].", "content": "Radioinduced acidity in solid state glucose is studied as a function of irradiation conditions (dose, dose rate, temperature, atmosphere composition), glucose characteristics (physical structure, water content) and post-irradiation treatments (presence of gas in dissolving water, storage).", "contents": "[The effect of irradiation conditions on the radioinduced acidity of solid phase glucose]. Radioinduced acidity in solid state glucose is studied as a function of irradiation conditions (dose, dose rate, temperature, atmosphere composition), glucose characteristics (physical structure, water content) and post-irradiation treatments (presence of gas in dissolving water, storage)."}
{"id": "PMID:239798", "title": "Glycoside inotropy in the absence of an increase in potassium efflux in the rabbit heart.", "content": "The inotropic effect of 1.25 times 10(-6)M acetylstrophanthidin (ACS) and the influx and efflux of labeled potassium (42K+) were studied in the arterially perfused rabbit interventricular septum under control conditions and during respiratory acidosis. An increase in the CO2 content of the gas mixture with which the modified Ringer's solution  was equilibrated from 5 to 30% reduced the perfusate pH from 7.37 to 6.66. The increment in developed tension in the presence of ACS was 3.0 +/- 0.2 g (n equals 10) under control conditions, but it was greater, 7.1 +/- 0.9 g (N equals 9) during acidosis (P less than less than 0.001). The net K+ loss due to an increase in K+ efflux was 1.8 +/- 0.2 mmoles/kg wet weight in control experiments but only 0.1 +/- 0.1 mmoles/kg net weight under acidotic conitions (P less than less than 0.001); in seven of nine experiments in respiratory acidosis, no increase in K+ efflux occurred despite a marked positive inotropy. In three septums, K+ influx was reduced by ACS during respiratory acidosis. These results demonstrate that during acidosis ACS inhibits sodium-potassium adenosinetriphosphatase (Na+-K+ ATPase) and causes an inotropic effect but does not increase K+ efflux. K+ efflux cannot be linked to calcium (Ca2+) influx or regarded as the controlling factor of glycoside-induced inotropy. The results give further support to the proposal that digitalis-induced inotropy is secondary to an enhancement of a Na+-Ca2+ exchange system.", "contents": "Glycoside inotropy in the absence of an increase in potassium efflux in the rabbit heart. The inotropic effect of 1.25 times 10(-6)M acetylstrophanthidin (ACS) and the influx and efflux of labeled potassium (42K+) were studied in the arterially perfused rabbit interventricular septum under control conditions and during respiratory acidosis. An increase in the CO2 content of the gas mixture with which the modified Ringer's solution  was equilibrated from 5 to 30% reduced the perfusate pH from 7.37 to 6.66. The increment in developed tension in the presence of ACS was 3.0 +/- 0.2 g (n equals 10) under control conditions, but it was greater, 7.1 +/- 0.9 g (N equals 9) during acidosis (P less than less than 0.001). The net K+ loss due to an increase in K+ efflux was 1.8 +/- 0.2 mmoles/kg wet weight in control experiments but only 0.1 +/- 0.1 mmoles/kg net weight under acidotic conitions (P less than less than 0.001); in seven of nine experiments in respiratory acidosis, no increase in K+ efflux occurred despite a marked positive inotropy. In three septums, K+ influx was reduced by ACS during respiratory acidosis. These results demonstrate that during acidosis ACS inhibits sodium-potassium adenosinetriphosphatase (Na+-K+ ATPase) and causes an inotropic effect but does not increase K+ efflux. K+ efflux cannot be linked to calcium (Ca2+) influx or regarded as the controlling factor of glycoside-induced inotropy. The results give further support to the proposal that digitalis-induced inotropy is secondary to an enhancement of a Na+-Ca2+ exchange system."}
{"id": "PMID:239799", "title": "Noninvasive assessment of aorta-coronary saphenous vein bypass graft patency using directional Doppler.", "content": "Noninvasive monitoring of patency of aorta-coronary bypass grafts can be achieved with reasonable accuracy using the continuous wave directional Doppler and a pencil probe. The character of the graphic record and the auditory signal generated by the flow through these new vessels perfusing the myocardium are distinctive because of both the pattern of flow and also the fixed and relatively immobile position of these grafts in the anterior mediastinum. A total of 226 aorta-coronary bypass grafts were monitored in the first postoperative week: 82 to the right coronary artery (RCA), 90 to the left anterior descending (LAD), and 56 to the circumflex and lateral ventricular branches. Interpretation of patency in these latter vessels was consistently unreliable and was abandoned early in the study. This unreliability was probably due to their short superficial course and their juxtaposition to the aorta and the pulmonary artery. In contrast, flow through grafts to the RCA and the LAD could be established in approximately 90%. Of 82 grafts to the RCA, flow could not be detected in four (5%) and was doubtful in two (2%). In 90 grafts to the LAD, no flow was observed in four (4%) and was doubtful in five (6%). Comparing noninvasive Doppler results with angiography in 34 grafts, no false negatives were found, but there were two or 10% false positives. Flow characteristics in a functioning internal mammary implant were also found to be quite different from those in an intact opposite mammary artery. This form of monitoring requires some practice and experience but is quick, cheap and noninvasive. It offers an acceptable degree of accuracy in monitoring aorta-coronary bypass grafts to the RCA and the LAD when the conduits are in the anterior mediastinum.", "contents": "Noninvasive assessment of aorta-coronary saphenous vein bypass graft patency using directional Doppler. Noninvasive monitoring of patency of aorta-coronary bypass grafts can be achieved with reasonable accuracy using the continuous wave directional Doppler and a pencil probe. The character of the graphic record and the auditory signal generated by the flow through these new vessels perfusing the myocardium are distinctive because of both the pattern of flow and also the fixed and relatively immobile position of these grafts in the anterior mediastinum. A total of 226 aorta-coronary bypass grafts were monitored in the first postoperative week: 82 to the right coronary artery (RCA), 90 to the left anterior descending (LAD), and 56 to the circumflex and lateral ventricular branches. Interpretation of patency in these latter vessels was consistently unreliable and was abandoned early in the study. This unreliability was probably due to their short superficial course and their juxtaposition to the aorta and the pulmonary artery. In contrast, flow through grafts to the RCA and the LAD could be established in approximately 90%. Of 82 grafts to the RCA, flow could not be detected in four (5%) and was doubtful in two (2%). In 90 grafts to the LAD, no flow was observed in four (4%) and was doubtful in five (6%). Comparing noninvasive Doppler results with angiography in 34 grafts, no false negatives were found, but there were two or 10% false positives. Flow characteristics in a functioning internal mammary implant were also found to be quite different from those in an intact opposite mammary artery. This form of monitoring requires some practice and experience but is quick, cheap and noninvasive. It offers an acceptable degree of accuracy in monitoring aorta-coronary bypass grafts to the RCA and the LAD when the conduits are in the anterior mediastinum."}
{"id": "PMID:239800", "title": "Blood flow and vasoactive drug effects in internal mammary and venous bypass grafts.", "content": "Cardiac output and pressure-flow measurements were made in left internal mammary artery-to-left anterior descending coronary artery grafts and left subclavian artery-to-left circumflex coronary artery vein grafts after proximal coronary artery ligation. Similar measurements were also made in left internal mammary artery-to-left anterior descending coronary artery grafts and aortocoronary saphenous vein grafts in patients with coronary artery disease. Hemodynamic parameters and graft blood flows were measured during control baseline conditions and after pharmacological interventions using isoproterenol, phenylephrine, and epinephrine in random order. Blood flow through vein grafts and internal mammary artery grafts was similar under basal conditions and increased similarly with each of these vasoactive agents. Other hemodynamic parameters changed variably with the various pharmacological agents used. There was no close correlation between mammary artery or vein graft blood flow and arterial mean pressure and cardiac output over the wide range observed with the different drugs was associated with either an increase in perfusion pressure or a decrease in coronary vascular resistance. If the percentage increase in coronary blood flow above the basal control value in response to pharmacological stress is considered as a reflection of coronary vascular reserve, these studies suggest that coronary vascular reserve in patients with coronary artery disease is less than that of the normal dog heart.", "contents": "Blood flow and vasoactive drug effects in internal mammary and venous bypass grafts. Cardiac output and pressure-flow measurements were made in left internal mammary artery-to-left anterior descending coronary artery grafts and left subclavian artery-to-left circumflex coronary artery vein grafts after proximal coronary artery ligation. Similar measurements were also made in left internal mammary artery-to-left anterior descending coronary artery grafts and aortocoronary saphenous vein grafts in patients with coronary artery disease. Hemodynamic parameters and graft blood flows were measured during control baseline conditions and after pharmacological interventions using isoproterenol, phenylephrine, and epinephrine in random order. Blood flow through vein grafts and internal mammary artery grafts was similar under basal conditions and increased similarly with each of these vasoactive agents. Other hemodynamic parameters changed variably with the various pharmacological agents used. There was no close correlation between mammary artery or vein graft blood flow and arterial mean pressure and cardiac output over the wide range observed with the different drugs was associated with either an increase in perfusion pressure or a decrease in coronary vascular resistance. If the percentage increase in coronary blood flow above the basal control value in response to pharmacological stress is considered as a reflection of coronary vascular reserve, these studies suggest that coronary vascular reserve in patients with coronary artery disease is less than that of the normal dog heart."}
{"id": "PMID:239801", "title": "The effect of vagus nerve stimulation upon vulnerability of the canine ventricle: role of sympathetic-parasympathetic interactions.", "content": "The effect of vagus nerve stimulation (VNS) upon ventricular vulnerability was studied in 30 mongrel dogs subjected to varying levels of adrenergic stimulation. Vulnerability was assessed both by determining the minimum current required to produce ventricular fibrillation (VF threshold) and by plotting VF threshold throughout the vulnerable period (VF zone). Chloralose-anesthetized animals were studied by means of sequential pulses applied to the apex of the right ventricular endocardium. Testing was carried out in closed-chest dogs, in open-chest dogs with and without left stellate ganglion stimulation (LSGS), and in open- and closed-chest dogs pretreated with propranolol. In the absence of adrenergic stimulation. VNS was without significant effect on either the VF threshold or the VF zone under closed- or open-chest conditions. During LSGS, however, VNS was associated with a 93 +/- 22% (mean +/- SE) increase in VF threshold (P less than 0.01) and constriction of the VF zone. Vagus nerve stimulation combined with LSGS raised VF threshold to the control value, but not beyond. After beta-adrenergic blockade with propranolol, VNS was without effect on VF threshold in either open- or closed-chest animals. It is concluded that augmented sympathetic tone is a precondition for a VNS-induced elevation in VF threshold. The vagal effect is indirect and is expressed by opposing the effects of heightened adrenergic tone on ventricular vulnerability.", "contents": "The effect of vagus nerve stimulation upon vulnerability of the canine ventricle: role of sympathetic-parasympathetic interactions. The effect of vagus nerve stimulation (VNS) upon ventricular vulnerability was studied in 30 mongrel dogs subjected to varying levels of adrenergic stimulation. Vulnerability was assessed both by determining the minimum current required to produce ventricular fibrillation (VF threshold) and by plotting VF threshold throughout the vulnerable period (VF zone). Chloralose-anesthetized animals were studied by means of sequential pulses applied to the apex of the right ventricular endocardium. Testing was carried out in closed-chest dogs, in open-chest dogs with and without left stellate ganglion stimulation (LSGS), and in open- and closed-chest dogs pretreated with propranolol. In the absence of adrenergic stimulation. VNS was without significant effect on either the VF threshold or the VF zone under closed- or open-chest conditions. During LSGS, however, VNS was associated with a 93 +/- 22% (mean +/- SE) increase in VF threshold (P less than 0.01) and constriction of the VF zone. Vagus nerve stimulation combined with LSGS raised VF threshold to the control value, but not beyond. After beta-adrenergic blockade with propranolol, VNS was without effect on VF threshold in either open- or closed-chest animals. It is concluded that augmented sympathetic tone is a precondition for a VNS-induced elevation in VF threshold. The vagal effect is indirect and is expressed by opposing the effects of heightened adrenergic tone on ventricular vulnerability."}
{"id": "PMID:239802", "title": "Lack of significant effect of L(+)-glutamate on serum gamma-glutamyltransferase activity determined in the presence of glycylglycine.", "content": "No increase in gamma-glutamyltransferase activity determined in human sera at 25, 30, or 37 degrees C could be demonstrated when L(+)-glutamate, 10 to 5000 mumol/liter, was incorporated into reaction media containing glycylglycine, 40 mmol/liter.", "contents": "Lack of significant effect of L(+)-glutamate on serum gamma-glutamyltransferase activity determined in the presence of glycylglycine. No increase in gamma-glutamyltransferase activity determined in human sera at 25, 30, or 37 degrees C could be demonstrated when L(+)-glutamate, 10 to 5000 mumol/liter, was incorporated into reaction media containing glycylglycine, 40 mmol/liter."}
{"id": "PMID:239803", "title": "Ultraviolet spectrophotometry of theophylline in plasma in the presence of barbiturates.", "content": "Ultraviolet spectrophotometry is widely used for the analysis of theophylline in blood, for purposes of monitoring therapy, and for pharmacokinetic studies. Phenobarbital, a component of common oral theophylline preparations, interferes with assays now in use. The modification of the method of Schack and Waxler [J. Pharmacol. Exp. Ther. 97, 283 (1949)] presented in this paper eliminates barbiturate interference. After solvent extraction and back extraction into NaOH, the pH of the alkaline solution is adjusted from pH 13 to 10 before spectrophotometric measurement. This shifts the barbiturate absorption maximum from 255 to 240 nm, permitting accurate analysis of theophylline, the spectrum of which is unaffected by the pH change.", "contents": "Ultraviolet spectrophotometry of theophylline in plasma in the presence of barbiturates. Ultraviolet spectrophotometry is widely used for the analysis of theophylline in blood, for purposes of monitoring therapy, and for pharmacokinetic studies. Phenobarbital, a component of common oral theophylline preparations, interferes with assays now in use. The modification of the method of Schack and Waxler [J. Pharmacol. Exp. Ther. 97, 283 (1949)] presented in this paper eliminates barbiturate interference. After solvent extraction and back extraction into NaOH, the pH of the alkaline solution is adjusted from pH 13 to 10 before spectrophotometric measurement. This shifts the barbiturate absorption maximum from 255 to 240 nm, permitting accurate analysis of theophylline, the spectrum of which is unaffected by the pH change."}
{"id": "PMID:239805", "title": "A successful new primary health care provider in the newborn nursery.", "content": "The mothers' acceptance of the Child Health Associate (\"CHA\") as a qualified health professional and the documentation of CHA's clinical abilities to provide broad-based health care for normal infants attest to their capabilities to function as primary health care providers in a newborn nursery. In \"low-risk\" nursery settings, where other capable health professionals may not be available, the CHA can assume primary and direct responsibility for the care of the normal newborn infant.", "contents": "A successful new primary health care provider in the newborn nursery. The mothers' acceptance of the Child Health Associate (\"CHA\") as a qualified health professional and the documentation of CHA's clinical abilities to provide broad-based health care for normal infants attest to their capabilities to function as primary health care providers in a newborn nursery. In \"low-risk\" nursery settings, where other capable health professionals may not be available, the CHA can assume primary and direct responsibility for the care of the normal newborn infant."}
{"id": "PMID:239806", "title": "Normal cardiac output during beta blockade with timolol in hypertensive patients.", "content": "Data published by this laboratory indicated that the beta adrenergic blocking drugs timolol and propranolol exerted equivalent beta blocking and antihypertensive actions in patients with mild essential hypertension, but that whereas cardiac output fell acutely with both drugs, it returned to normal after 5 wk of treatment with timolol, but remained depressed after propranolol. This preliminary observation needed further confirmation in a larger series of patients. In this study, 11 patients with initial diastolic blood pressures between 90 and 125 mm Hg were given timolol for 5 wk. Hemodynamic measurements were made before and at the end of treatment. Mean heart rate fell from 76.8 to 64.3 bpm (p less than 0.001), and blood pressure was reduced from 179.4/99 mm Hg to 167.4/93.3 mm Hg (less than 0.02). Cardiac  output averaged 6.29 L/min before timolol, and fell to 5.95 L/min (NS) after treatment. Stroke volume increased significantly, while total peripheral resistance was unchanged. These results confirm our earlier observations that timolol is an effective beta adrenergic blocking drug with antihypertensive action that does not reduce cardiac output significantly when given chronically. This drug merits further evaluation in other cardiovascular disorders since it may have advantages over other beta adrenergic blocking drugs.", "contents": "Normal cardiac output during beta blockade with timolol in hypertensive patients. Data published by this laboratory indicated that the beta adrenergic blocking drugs timolol and propranolol exerted equivalent beta blocking and antihypertensive actions in patients with mild essential hypertension, but that whereas cardiac output fell acutely with both drugs, it returned to normal after 5 wk of treatment with timolol, but remained depressed after propranolol. This preliminary observation needed further confirmation in a larger series of patients. In this study, 11 patients with initial diastolic blood pressures between 90 and 125 mm Hg were given timolol for 5 wk. Hemodynamic measurements were made before and at the end of treatment. Mean heart rate fell from 76.8 to 64.3 bpm (p less than 0.001), and blood pressure was reduced from 179.4/99 mm Hg to 167.4/93.3 mm Hg (less than 0.02). Cardiac  output averaged 6.29 L/min before timolol, and fell to 5.95 L/min (NS) after treatment. Stroke volume increased significantly, while total peripheral resistance was unchanged. These results confirm our earlier observations that timolol is an effective beta adrenergic blocking drug with antihypertensive action that does not reduce cardiac output significantly when given chronically. This drug merits further evaluation in other cardiovascular disorders since it may have advantages over other beta adrenergic blocking drugs."}
{"id": "PMID:239807", "title": "Respiratory effects of lorazepam, pentobarbital, and pentazocine.", "content": "The respiratory effects of a new benzodiazepine, lorazepam, were compared to those of pentobarbital and pentazocine.  Pentobarbital, 50 and 150 mg, produced respiratory depression, as did pentazocine, 30 mg intramuscularly.  Lorazepam at 1.33 and 4 mg intramuscularly produced none.", "contents": "Respiratory effects of lorazepam, pentobarbital, and pentazocine. The respiratory effects of a new benzodiazepine, lorazepam, were compared to those of pentobarbital and pentazocine.  Pentobarbital, 50 and 150 mg, produced respiratory depression, as did pentazocine, 30 mg intramuscularly.  Lorazepam at 1.33 and 4 mg intramuscularly produced none."}
{"id": "PMID:239836", "title": "Activity of doxycycline against respiratory pathogens.", "content": "149 patients were admitted from the Brussels area to the multi-centre Pan European trial of doxycycline in respiratory tract infections. Of these, 40 satisfied the strict criteria for detailed bacteriological study with positive culture of a known pathogen before treatment and bacteriological follow-up after treatment. The pathogens were beta-haemolytic streptococcus, group A (29 cases), pneumococcus (6 cases) and Haemophilus influenzae (6 cases); in one case, the pneumococcus and H. influenzae were present together. The results of doxycycline therapy were excellent, this included both its in vivo and in vitro activity; only one strain of pneumococcus proved resistant.", "contents": "Activity of doxycycline against respiratory pathogens. 149 patients were admitted from the Brussels area to the multi-centre Pan European trial of doxycycline in respiratory tract infections. Of these, 40 satisfied the strict criteria for detailed bacteriological study with positive culture of a known pathogen before treatment and bacteriological follow-up after treatment. The pathogens were beta-haemolytic streptococcus, group A (29 cases), pneumococcus (6 cases) and Haemophilus influenzae (6 cases); in one case, the pneumococcus and H. influenzae were present together. The results of doxycycline therapy were excellent, this included both its in vivo and in vitro activity; only one strain of pneumococcus proved resistant."}
{"id": "PMID:239837", "title": "Doxycycline in respiratory tract infections. A review of a multi-centre trial.", "content": "A total of 256 patients were admitted in Germany into a Pan-European multi centre trial of doxycycline in the treatment of infections of the respiratory tract. The diagnoses showed a preponderance of lower respiratory tract infections compared with other European countries, due largely to the fact that the participating physicians were pulmonary or internal medicine specialists. Doxycycline was given in a dose of 200 mg initially followed by 100 mg daily for 5-10 days (only the occasional patient varied from this regimen). Side-effects were uncommon (2.5-3.5%) and affected only the gastrointestinal tract. Four patients had to change antibiotic therapy, not because of side-effects but because of possible bacterial resistance in these patients. The results were comparable with those from the rest of Europe: 88% of patients had a good or very good response. Nine patients were treated for longer than 14 days and only eight patients did not show improvement.", "contents": "Doxycycline in respiratory tract infections. A review of a multi-centre trial. A total of 256 patients were admitted in Germany into a Pan-European multi centre trial of doxycycline in the treatment of infections of the respiratory tract. The diagnoses showed a preponderance of lower respiratory tract infections compared with other European countries, due largely to the fact that the participating physicians were pulmonary or internal medicine specialists. Doxycycline was given in a dose of 200 mg initially followed by 100 mg daily for 5-10 days (only the occasional patient varied from this regimen). Side-effects were uncommon (2.5-3.5%) and affected only the gastrointestinal tract. Four patients had to change antibiotic therapy, not because of side-effects but because of possible bacterial resistance in these patients. The results were comparable with those from the rest of Europe: 88% of patients had a good or very good response. Nine patients were treated for longer than 14 days and only eight patients did not show improvement."}
{"id": "PMID:239843", "title": "[Symptoms and clinical features of panarteritis nodosa (author's transl)].", "content": "Panarteritis nodosa was diagnosed in five patients, two of whom died shortly thereafter, while three are followed now up to four years. Clinical and biochemical findings will give the first diagnostic pointer to panarteritis nodosa, while the only proof can be by biopsy of the affected organ. Prognosis varies and must be assessed cautiously in the individual case. Type, extent and number of organs involved are of decisive role prognostically. An allergic-hyperergic reaction of the vessels walls is thought to be the cause. Corticosteroids and immunosuppressives may be used therapeutically. The neuromuscular form of panarteritis responds quite well to this form of medication, but prognosis depends on whether there is also visceral involvement.", "contents": "[Symptoms and clinical features of panarteritis nodosa (author's transl)]. Panarteritis nodosa was diagnosed in five patients, two of whom died shortly thereafter, while three are followed now up to four years. Clinical and biochemical findings will give the first diagnostic pointer to panarteritis nodosa, while the only proof can be by biopsy of the affected organ. Prognosis varies and must be assessed cautiously in the individual case. Type, extent and number of organs involved are of decisive role prognostically. An allergic-hyperergic reaction of the vessels walls is thought to be the cause. Corticosteroids and immunosuppressives may be used therapeutically. The neuromuscular form of panarteritis responds quite well to this form of medication, but prognosis depends on whether there is also visceral involvement."}
{"id": "PMID:239844", "title": "An assay for erythropoietin in vitro at the milliunit level.", "content": "A method is described for the assay of erythropoietin using primary cultures of adult rat bone marrow cells. Either total labeled iron uptake by the cells or hematin synthesis from labeled iron may be used as the measure of erythropoietin action. The method is useful in the range 0.001 to 0.010 U, where the log response is linear with the log dose, and can be carried out in 2 working days. This method has the disadvantage of detecting asialoerythropoietin which has no activity in vivo.", "contents": "An assay for erythropoietin in vitro at the milliunit level. A method is described for the assay of erythropoietin using primary cultures of adult rat bone marrow cells. Either total labeled iron uptake by the cells or hematin synthesis from labeled iron may be used as the measure of erythropoietin action. The method is useful in the range 0.001 to 0.010 U, where the log response is linear with the log dose, and can be carried out in 2 working days. This method has the disadvantage of detecting asialoerythropoietin which has no activity in vivo."}
{"id": "PMID:239845", "title": "Beta2-adrenergic stimulation of thyroid hormone secretion.", "content": "The influence on thyroid hormone secretion of the nonselective beta-adrenergic stimulant isoproterenol (IPNE), of a selective beta1-adrenergic stimulant, 1-isopropylamino-3-(2-thiazoloxy)-2-propanol (ITP), and of a selective beta2-adrenergic stimulant, terbutaline, was investigated in mice. A combination of light microscopy (colloid droplet formation) and bioassay (blood radioiodine--BRI--measurements) was used. IPNE and terbutaline induced formation of colloid droplets and increased BRI levels, whereas ITP was ineffective. The responses to IPNE and terbutaline were abolished or reduced by pretreatment with L-propranolol, but were not inhibited for pretreatment with D-propranolol or phentolamine. The results indicate that secretion of thyroid hormone can be induced through the mediation of beta2-adrenergic receptors.", "contents": "Beta2-adrenergic stimulation of thyroid hormone secretion. The influence on thyroid hormone secretion of the nonselective beta-adrenergic stimulant isoproterenol (IPNE), of a selective beta1-adrenergic stimulant, 1-isopropylamino-3-(2-thiazoloxy)-2-propanol (ITP), and of a selective beta2-adrenergic stimulant, terbutaline, was investigated in mice. A combination of light microscopy (colloid droplet formation) and bioassay (blood radioiodine--BRI--measurements) was used. IPNE and terbutaline induced formation of colloid droplets and increased BRI levels, whereas ITP was ineffective. The responses to IPNE and terbutaline were abolished or reduced by pretreatment with L-propranolol, but were not inhibited for pretreatment with D-propranolol or phentolamine. The results indicate that secretion of thyroid hormone can be induced through the mediation of beta2-adrenergic receptors."}
{"id": "PMID:239846", "title": "Influence of the neuroleptanalgesic combination of etorphine and acepromazine on the horse: blood gases and acid-base balance.", "content": "Respiratory function and acid-base variables were studied in Welsh Mountain ponies before and at predetermined times after the intravenous injection of Immobilon and Revivon.A marked depression of respiratory rate was accompanied by large reductions in arterial blood oxygen tension and saturation and the development of a mild respiratory acidosis following the injection of Immobilon. It was concluded that at least three factors contributed to the hypoxic hypoxia produced by Immobilon; the posture of lateral recumbency, the decrease in respiratory rate and the laboured character of the respiration. Arterial oxygen and carbon dioxide tensions returned towards control levels soon after administering Revivon. Mixed venous oxygen tensions were little affected by either Immobilon or Revivon,  and mixed venous carbon dioxide tensions were increased to smaller degrees that those of arterial blood. Haemoglobin was increased initially by Immobilon, had returned to the control level by 30 min and fell below the control following the administration of Revivon.", "contents": "Influence of the neuroleptanalgesic combination of etorphine and acepromazine on the horse: blood gases and acid-base balance. Respiratory function and acid-base variables were studied in Welsh Mountain ponies before and at predetermined times after the intravenous injection of Immobilon and Revivon.A marked depression of respiratory rate was accompanied by large reductions in arterial blood oxygen tension and saturation and the development of a mild respiratory acidosis following the injection of Immobilon. It was concluded that at least three factors contributed to the hypoxic hypoxia produced by Immobilon; the posture of lateral recumbency, the decrease in respiratory rate and the laboured character of the respiration. Arterial oxygen and carbon dioxide tensions returned towards control levels soon after administering Revivon. Mixed venous oxygen tensions were little affected by either Immobilon or Revivon,  and mixed venous carbon dioxide tensions were increased to smaller degrees that those of arterial blood. Haemoglobin was increased initially by Immobilon, had returned to the control level by 30 min and fell below the control following the administration of Revivon."}
{"id": "PMID:239853", "title": "Hematopoietic differentiative properties of murine spleen implanted in the omenta of irradiated and nonirradiated hosts.", "content": "Whole body irradiation of the recipients of syngeneic splenic implants into the omentum greatly enchances hematopoiesis and permits survial of and repopulation by stem cells of donor origin. Donor hematopioetic stem cells do not survive in spleen implants of the nonirradiated host; irradiated hosts were therfore used in the bulk of the experiments. Differentiation in the implants of splenic fragments is predominantly erythrocytic at 10 days and shifts to predominantly granulocytic differentiation at 21 days. Suspensions of spleen cells injected into the ometntum are predominantly granulocytopioetic at 10 days. The differntiation in fragments of spleen depleted of stem cells by irradtion, seeded with bone marrow cells and implanted into the omentum results in mixed erythocytic and granulocytic hematopoiesis, with granulocytic predominance. Lymphocytic cells appeared late in the implants of irrdiated recipients even at a time of prolific lymphocytopoiesis in the host's own spleens. The cause of the delay in the implants is not clear. The data are consisent with the concept that differntiation of hematopioetic stem cells is influenced by the stromal cells of the parent organ. The erythrocytic inductive capacity of the stromal cells may be lost by mechanical disruption or modified by irraidation or a prolonged period of implantation.", "contents": "Hematopoietic differentiative properties of murine spleen implanted in the omenta of irradiated and nonirradiated hosts. Whole body irradiation of the recipients of syngeneic splenic implants into the omentum greatly enchances hematopoiesis and permits survial of and repopulation by stem cells of donor origin. Donor hematopioetic stem cells do not survive in spleen implants of the nonirradiated host; irradiated hosts were therfore used in the bulk of the experiments. Differentiation in the implants of splenic fragments is predominantly erythrocytic at 10 days and shifts to predominantly granulocytic differentiation at 21 days. Suspensions of spleen cells injected into the ometntum are predominantly granulocytopioetic at 10 days. The differntiation in fragments of spleen depleted of stem cells by irradtion, seeded with bone marrow cells and implanted into the omentum results in mixed erythocytic and granulocytic hematopoiesis, with granulocytic predominance. Lymphocytic cells appeared late in the implants of irrdiated recipients even at a time of prolific lymphocytopoiesis in the host's own spleens. The cause of the delay in the implants is not clear. The data are consisent with the concept that differntiation of hematopioetic stem cells is influenced by the stromal cells of the parent organ. The erythrocytic inductive capacity of the stromal cells may be lost by mechanical disruption or modified by irraidation or a prolonged period of implantation."}
{"id": "PMID:239854", "title": "Evaluation of biologic activity of ferric chloride-treated endotoxin in mice.", "content": "Endotoxin (lipopolysaccharide, LPS) treated with ferric chloride was tested for its potential as a non-toxic agent for enhancement of non-specific host resistance. A 1 mg dose of untreated endotoxin, injected i.p. into mice, resulted in 100 per cent mortality, whereas the same amount of chemically-treated endotoxin resulted in less than 35 per cent lethality. The radio-protective potential of the treated endotoxin was similar to that of untreated endotoxin, as 70 per cent of each group of mice tested with either substance survived a dose of 850 rad x-ray. Irradiated mice, challenged 8 days after 850 rad x-irradiation, died when injected with 25 mug of either untreated or treated endotoxin. Antibiotic decontamination of the intestinal tract of host animals reduced the possibility of toxicity from endogenous endotoxin after challenge. This treatment resulted in 100 per cent survival from a 25 mug challenge at 8 days post-irradiation. The ferric chloride-treated proved to be a more effective B-lymphocyte mitogen. At a dose of 100 mug, treated endotoxin resulted in a 50 per cent greater mitogenic stimulation of B-lymphocytes as compared with that found after exposure to untreated endotoxin. Several lines of evidence support the contention that tolerance to untreated endotoxin was induced by repeated injections of either endotoxin preparation 1) 100 per cent of all endotoxin-tolerant mice survived a 1 mg challenge dose of untreated endotoxin, 2) there was a reduced mitotic response of splenic B-lymphocytes after re-exposure with untreated endotoxin as compared with that observed for cells derived from saline-treated mice, and 3) all antibiotic decontaminated mice engrafted with spleen cells from mice made tolerant to either endotoxin preparation survive graft-versus-host disease. In conclusion, based on survival data from normal mice, ferric chloride-treated endotoxin is safer to use than normal endotoxin. Also, treated endotoxin can elicit biologic responses similar in magnitude to those found after injection of mice with untreated endotoxin.", "contents": "Evaluation of biologic activity of ferric chloride-treated endotoxin in mice. Endotoxin (lipopolysaccharide, LPS) treated with ferric chloride was tested for its potential as a non-toxic agent for enhancement of non-specific host resistance. A 1 mg dose of untreated endotoxin, injected i.p. into mice, resulted in 100 per cent mortality, whereas the same amount of chemically-treated endotoxin resulted in less than 35 per cent lethality. The radio-protective potential of the treated endotoxin was similar to that of untreated endotoxin, as 70 per cent of each group of mice tested with either substance survived a dose of 850 rad x-ray. Irradiated mice, challenged 8 days after 850 rad x-irradiation, died when injected with 25 mug of either untreated or treated endotoxin. Antibiotic decontamination of the intestinal tract of host animals reduced the possibility of toxicity from endogenous endotoxin after challenge. This treatment resulted in 100 per cent survival from a 25 mug challenge at 8 days post-irradiation. The ferric chloride-treated proved to be a more effective B-lymphocyte mitogen. At a dose of 100 mug, treated endotoxin resulted in a 50 per cent greater mitogenic stimulation of B-lymphocytes as compared with that found after exposure to untreated endotoxin. Several lines of evidence support the contention that tolerance to untreated endotoxin was induced by repeated injections of either endotoxin preparation 1) 100 per cent of all endotoxin-tolerant mice survived a 1 mg challenge dose of untreated endotoxin, 2) there was a reduced mitotic response of splenic B-lymphocytes after re-exposure with untreated endotoxin as compared with that observed for cells derived from saline-treated mice, and 3) all antibiotic decontaminated mice engrafted with spleen cells from mice made tolerant to either endotoxin preparation survive graft-versus-host disease. In conclusion, based on survival data from normal mice, ferric chloride-treated endotoxin is safer to use than normal endotoxin. Also, treated endotoxin can elicit biologic responses similar in magnitude to those found after injection of mice with untreated endotoxin."}
{"id": "PMID:239857", "title": "Gastric secretion during anaesthesia and its inhibition by metiamide and other drugs.", "content": "The histamine H2-receptor antagonist, metiamide, inhibits the acid gastric secretion produced by chloralose-urethane anaesthesia in dogs carrying gastric cannulae chronically. This secretion is also prevented by atropine and hexamethonium. \"Spontaneous\" gastric secretion of vagal origin in conscious dogs is also blocked by metiamide.", "contents": "Gastric secretion during anaesthesia and its inhibition by metiamide and other drugs. The histamine H2-receptor antagonist, metiamide, inhibits the acid gastric secretion produced by chloralose-urethane anaesthesia in dogs carrying gastric cannulae chronically. This secretion is also prevented by atropine and hexamethonium. \"Spontaneous\" gastric secretion of vagal origin in conscious dogs is also blocked by metiamide."}
{"id": "PMID:239858", "title": "Uterine secretion during the sexual cycle in the rat and its capacity to disperse corona cells in vitro.", "content": "It was found that closure of the uterus disturbed the first 2 cycles after the operation; thereafter the normal cycle was resumed. The quantity of uterine fluid was increased at pro-oestrus and oestrus and reduced at met-oestrus and di-oestrus. Slight inverse changes in viscosity were observed. There was no significant difference in the pH. The corona-cell dispersing factor seems to be an oestrogen-dependent constituent of uterine secretion.", "contents": "Uterine secretion during the sexual cycle in the rat and its capacity to disperse corona cells in vitro. It was found that closure of the uterus disturbed the first 2 cycles after the operation; thereafter the normal cycle was resumed. The quantity of uterine fluid was increased at pro-oestrus and oestrus and reduced at met-oestrus and di-oestrus. Slight inverse changes in viscosity were observed. There was no significant difference in the pH. The corona-cell dispersing factor seems to be an oestrogen-dependent constituent of uterine secretion."}
{"id": "PMID:239871", "title": "[A study on the determination method of cyclic AMP in urine by competitive protein binding assay (author's transl)].", "content": "The determination method of c-AMP in urine by competitive protein binding assay using the Boehringer Mannheim Laboratory kit was investigated and the results obtained were as follows. 1) Since the angle of the inclination of the standard curve was large, the present method could be used for the determination of c-AMP in concentrations of from 0 to 20p moles. 2) The optimal condition of the binding reaction was for 100 minutes of reaction time at pH 4.0 and 4 degrees C. 3) The specificities of binding protein to the other nucleotides were 0 to adenosine, 0.4 to AMP, 0.3 to ADP, 0.4 to ATP and 0.6 to c-GMP respectively when the specificity to c-AMP was chosen as 100. 4) The optimal volume of cold phosphate buffer solution needed for washing to separate binding c-AMP by filtration method using a millipore filter was 5 approximately 15 ml. 5) The precision of the present method by double determination was 0 arrroximately +/- 11.1% with average of +/-5.6% in c.v. 6) The recovery rate of the added c-AMP by the present method was 78.6 approximately 105.6% with average of 90.1%. 7) Correlation between the determination values of c-AMP of the same samples with the present method and radioimmunosasay (Schwarzman Laboratory Kit) was satisfactorily high with 0.890 in coefficient of correlation, and the determination values by the present method were significantly higher (p less than 0.05) than those by radioimmunoassay. 8) C-AMP in urine was stable for at least one month when the urine was kept frozen. It is conclusively considered from the above results that this competitive protein binding assay is a method to determine c-AMP in urine with excellent accuracy and sensitivity and that this method is useful for clinical test.", "contents": "[A study on the determination method of cyclic AMP in urine by competitive protein binding assay (author's transl)]. The determination method of c-AMP in urine by competitive protein binding assay using the Boehringer Mannheim Laboratory kit was investigated and the results obtained were as follows. 1) Since the angle of the inclination of the standard curve was large, the present method could be used for the determination of c-AMP in concentrations of from 0 to 20p moles. 2) The optimal condition of the binding reaction was for 100 minutes of reaction time at pH 4.0 and 4 degrees C. 3) The specificities of binding protein to the other nucleotides were 0 to adenosine, 0.4 to AMP, 0.3 to ADP, 0.4 to ATP and 0.6 to c-GMP respectively when the specificity to c-AMP was chosen as 100. 4) The optimal volume of cold phosphate buffer solution needed for washing to separate binding c-AMP by filtration method using a millipore filter was 5 approximately 15 ml. 5) The precision of the present method by double determination was 0 arrroximately +/- 11.1% with average of +/-5.6% in c.v. 6) The recovery rate of the added c-AMP by the present method was 78.6 approximately 105.6% with average of 90.1%. 7) Correlation between the determination values of c-AMP of the same samples with the present method and radioimmunosasay (Schwarzman Laboratory Kit) was satisfactorily high with 0.890 in coefficient of correlation, and the determination values by the present method were significantly higher (p less than 0.05) than those by radioimmunoassay. 8) C-AMP in urine was stable for at least one month when the urine was kept frozen. It is conclusively considered from the above results that this competitive protein binding assay is a method to determine c-AMP in urine with excellent accuracy and sensitivity and that this method is useful for clinical test."}
{"id": "PMID:239872", "title": "Effect of phenformin on gluconeogenesis from lactate and intracellular pH in the isolated perfused guinea pig liver.", "content": "Gluconeogenesis from lactate and hepatic cell pH (pHi) were measured in the isolated perfused livers of starved guinea pigs in the presence and absence of phenformin (phenethylbiguanide). The observed decrease in lactate consumption and glucose output in the presence of phenformin was associated with a fall in pHi. The fall in glucose output observed was considerably greater than accountable for by the decrease in lactate consumption. A possible mechanism for the pathogenesis of clinical lactic acidosis due to phenformin therapy is suggested.", "contents": "Effect of phenformin on gluconeogenesis from lactate and intracellular pH in the isolated perfused guinea pig liver. Gluconeogenesis from lactate and hepatic cell pH (pHi) were measured in the isolated perfused livers of starved guinea pigs in the presence and absence of phenformin (phenethylbiguanide). The observed decrease in lactate consumption and glucose output in the presence of phenformin was associated with a fall in pHi. The fall in glucose output observed was considerably greater than accountable for by the decrease in lactate consumption. A possible mechanism for the pathogenesis of clinical lactic acidosis due to phenformin therapy is suggested."}
{"id": "PMID:239881", "title": "Generation of free radicals of quinone group-containing anti-cancer chemicals in NADPH-microsome system as evidenced by initiation of sulfite oxidation.", "content": "The prerequisit of reduction for activation of Mitomycin-C and unstability of its reduced form suggested investigation of the possible formation of free radicals (semiquinone forms) of a series of quinone-containing anticancer chemicals in vitro. The ability of rat-liver microsomes to initiate sulfite oxidation in the presence of NADPH was markedly enhanced by the addition of these chemicals. This strongly suggests that these chemicals participated in the process in the form of reactive free radicals. The reaction was specific for NADPH. Carbazilquinone was unique among others in that NADH can replace NADPH and its higher ability to initiate sulfite oxidation. Microsomes from Ehrlich ascites and AH-109A hepatoma cells were also effective, though to a lesser extent than those from rat liver on a protein basis. Generation of free radicals, though their biological significance is not clear at present, may be deemed an inherent chemical property of these chemicals.", "contents": "Generation of free radicals of quinone group-containing anti-cancer chemicals in NADPH-microsome system as evidenced by initiation of sulfite oxidation. The prerequisit of reduction for activation of Mitomycin-C and unstability of its reduced form suggested investigation of the possible formation of free radicals (semiquinone forms) of a series of quinone-containing anticancer chemicals in vitro. The ability of rat-liver microsomes to initiate sulfite oxidation in the presence of NADPH was markedly enhanced by the addition of these chemicals. This strongly suggests that these chemicals participated in the process in the form of reactive free radicals. The reaction was specific for NADPH. Carbazilquinone was unique among others in that NADH can replace NADPH and its higher ability to initiate sulfite oxidation. Microsomes from Ehrlich ascites and AH-109A hepatoma cells were also effective, though to a lesser extent than those from rat liver on a protein basis. Generation of free radicals, though their biological significance is not clear at present, may be deemed an inherent chemical property of these chemicals."}
{"id": "PMID:239882", "title": "Comparison of gastric mucosal blood flow as determined by aminopyrine clearance and gamma-labeled microspheres.", "content": "Gastric mucosal blood flow was simultaneously determined by aminopyrine clearance and gamma-labeled microspheres (15 +/- 5 mu in diameter) in anesthetized dogs prepared with a chambered segment of stomach greater curvature. Paired flow measurements were made in 11 dogs (n = 28) secreting in response to intravenous histamine (1mug per kg per min), in 11 (n = 21) nonsecreting dogs given intravenous isoproterenol (0.5 or 1.0 mug per kg per min), and in 9 (n = 10) dogs given no drugs to stimulate secretion or blood flow (resting dogs). Eight additional injections were done in dogs receiving various combinations of isoproterenol and histamine. Isotonic HCl was maintained on the mucosal surface during all experiments. Regression analysis demonstrated a highly significant linear correlation between clearance and microsphere-measured flow in the histamine (P less than 0.001, r = 0.96) and isoproterenol (P less than 0.001, r = 0.78) experiments, with clearance averaging 83% of microsphere flow during histamine stimulation but only 25% during isoproterenol. The relationship between clearance and microsphere flow was not significantly different for the resting and isoproterenol experiments. Mucosal perfusion measured by microspheres was about 5 times the resting value for both histamine and isoproterenol-stimulated dogs. Perfusion calculated from aminopyrine clearance averaged 46, 38, and 90% of the microsphere value in the resting, isoproterenol, and histamine experiments, respectively. Pooled data from secreting dogs demonstrated a fairly constant ratio of microsphere-measured flow to clearance (1.25 +/- 0.06 mean +/- SEM), regardless of the secretory rate. Our results indicate that aminopyrine clearance reflects only a small fraction of mucosal blood flow in the nonsecreting stomach, even in the presence of exogenous acid.", "contents": "Comparison of gastric mucosal blood flow as determined by aminopyrine clearance and gamma-labeled microspheres. Gastric mucosal blood flow was simultaneously determined by aminopyrine clearance and gamma-labeled microspheres (15 +/- 5 mu in diameter) in anesthetized dogs prepared with a chambered segment of stomach greater curvature. Paired flow measurements were made in 11 dogs (n = 28) secreting in response to intravenous histamine (1mug per kg per min), in 11 (n = 21) nonsecreting dogs given intravenous isoproterenol (0.5 or 1.0 mug per kg per min), and in 9 (n = 10) dogs given no drugs to stimulate secretion or blood flow (resting dogs). Eight additional injections were done in dogs receiving various combinations of isoproterenol and histamine. Isotonic HCl was maintained on the mucosal surface during all experiments. Regression analysis demonstrated a highly significant linear correlation between clearance and microsphere-measured flow in the histamine (P less than 0.001, r = 0.96) and isoproterenol (P less than 0.001, r = 0.78) experiments, with clearance averaging 83% of microsphere flow during histamine stimulation but only 25% during isoproterenol. The relationship between clearance and microsphere flow was not significantly different for the resting and isoproterenol experiments. Mucosal perfusion measured by microspheres was about 5 times the resting value for both histamine and isoproterenol-stimulated dogs. Perfusion calculated from aminopyrine clearance averaged 46, 38, and 90% of the microsphere value in the resting, isoproterenol, and histamine experiments, respectively. Pooled data from secreting dogs demonstrated a fairly constant ratio of microsphere-measured flow to clearance (1.25 +/- 0.06 mean +/- SEM), regardless of the secretory rate. Our results indicate that aminopyrine clearance reflects only a small fraction of mucosal blood flow in the nonsecreting stomach, even in the presence of exogenous acid."}
{"id": "PMID:239883", "title": "Chemicals bathing the oxyntic gland area stimulate acid secretion in dog.", "content": "Release of gastrin is the only recognized mechanism by which chemicals in the stomach stimulate acid secretion. We report here that dietary components coming in contact only with oxyntic gland mucosa stimulate near maximal acid secretion through a local, H-sensitive mechanism that does not involve gastrin. In 4 dogs with gastric fistula and Heidenhain pouch (HP), 10% liver extract, 10% peptone, 0.4 M glycine, or Tris buffer, as control, was instilled into the HP in volumes of 40, 80, or 160 ml every 30 min. Instilled solutions were adjusted to pH 8.0 and HP acid secretion was measured by titrating a sample of the fluid recovered from the HP back to pH 8.0 with 0.2 M NaOH. Instillation of liver extract into the HP stimulated acid secretion from the HP but caused no change in serum gastrin and no change in acid secretion from the gastric fistula. The maximal response to liver extract occurred with the largest volume instilled and was 80% of the maximal response to histamine and 188% of the maximal response to pentagastrin. Expressed as per cent of maximal response to histamine, the maximal response to Tris buffer was 8%, to peptone 44%, and to glycine 14%. Intact bovine serum albumin gave no response, but after digestion by pepsin it stimulated acid secretion moderately. At pH 2.0, liver extract caused no stimulation of acid secretion. The pH threshold was about 2.5, and at pH 4.5 acid secretion was 55% of the response at pH 8.0. The response to liver extract at pH 8.0 was only minimally decreased by topical lidocaine or by intravenous atropine or metiamide. Since atropine and metiamide almost totally abolish the acid response to food in the main stomach, but do not inhibit secretion of acid evoked by instilling liver extract into the HP, there is reason to doubt whether this new mechanism operates under physiological conditions.", "contents": "Chemicals bathing the oxyntic gland area stimulate acid secretion in dog. Release of gastrin is the only recognized mechanism by which chemicals in the stomach stimulate acid secretion. We report here that dietary components coming in contact only with oxyntic gland mucosa stimulate near maximal acid secretion through a local, H-sensitive mechanism that does not involve gastrin. In 4 dogs with gastric fistula and Heidenhain pouch (HP), 10% liver extract, 10% peptone, 0.4 M glycine, or Tris buffer, as control, was instilled into the HP in volumes of 40, 80, or 160 ml every 30 min. Instilled solutions were adjusted to pH 8.0 and HP acid secretion was measured by titrating a sample of the fluid recovered from the HP back to pH 8.0 with 0.2 M NaOH. Instillation of liver extract into the HP stimulated acid secretion from the HP but caused no change in serum gastrin and no change in acid secretion from the gastric fistula. The maximal response to liver extract occurred with the largest volume instilled and was 80% of the maximal response to histamine and 188% of the maximal response to pentagastrin. Expressed as per cent of maximal response to histamine, the maximal response to Tris buffer was 8%, to peptone 44%, and to glycine 14%. Intact bovine serum albumin gave no response, but after digestion by pepsin it stimulated acid secretion moderately. At pH 2.0, liver extract caused no stimulation of acid secretion. The pH threshold was about 2.5, and at pH 4.5 acid secretion was 55% of the response at pH 8.0. The response to liver extract at pH 8.0 was only minimally decreased by topical lidocaine or by intravenous atropine or metiamide. Since atropine and metiamide almost totally abolish the acid response to food in the main stomach, but do not inhibit secretion of acid evoked by instilling liver extract into the HP, there is reason to doubt whether this new mechanism operates under physiological conditions."}
{"id": "PMID:239886", "title": "Distribution of Cryptococcus neoformans in a pigeon habitat.", "content": "Samples of pigeon droppings were taken from 7 sites in a church tower contaminated with C. neoformans, and the distribution patterns of the fungus were studied. From various sites, 0 to 3 x 10(5) viable C. neoformans particles were recovered per one gram of dry excreta. The factors causing the different density of C. neoformans population in the habitat were: uric acid share of the total nitrogen, creatinine content, sunlight and probably pH. Chemical composition of the substrate is the primary factor in the distribution of C. neoformans in droppings.", "contents": "Distribution of Cryptococcus neoformans in a pigeon habitat. Samples of pigeon droppings were taken from 7 sites in a church tower contaminated with C. neoformans, and the distribution patterns of the fungus were studied. From various sites, 0 to 3 x 10(5) viable C. neoformans particles were recovered per one gram of dry excreta. The factors causing the different density of C. neoformans population in the habitat were: uric acid share of the total nitrogen, creatinine content, sunlight and probably pH. Chemical composition of the substrate is the primary factor in the distribution of C. neoformans in droppings."}
{"id": "PMID:239887", "title": "[Pharmacological action of [ethyl p(6-guanidinohexanoyloxy)benzoate] methanesulfonate (FOY)].", "content": "General pharmacological effects of [Ethyl p-(6-guanidinohexanoyloxy)benzoate] methanesulfonate (FOY), a new antiproteolytic agent, were studied and the following results were obtained. Acute administration of large doses of FOY in conscious dogs and rabbits caused a decrease in spontaneous motility, ataxia, cyanosis, collapse, mydriasis, and respiratory paralysis. The agent had no effect on the central nervous system and exhibited hypotensive effects in dogs in doses of more than 1 mg/kg. Hypotensive responses were not inhibited by treatment with atropine or hexamethonium. FOY had no effects on ECG in the rabbit at doses of less than 30 mg/kg and at doses from 10(-6) to 10(-4)g/ml, distinctly reduced the amplitude of the spontaneous and rhythmic contractions of the isolated rabbit ileum, guinea-pig ileum and rat uterus preparation. The contractile response to nerve stimulation, noradrenaline and barium was suppressed in isolated guinea-pig vas deferens. FOY had no effects on the twitch response of gastrocnemius muscle to sciatic nerve stimulation in rats. The drug caused local irritant effects in rabbits and rats.", "contents": "[Pharmacological action of [ethyl p(6-guanidinohexanoyloxy)benzoate] methanesulfonate (FOY)]. General pharmacological effects of [Ethyl p-(6-guanidinohexanoyloxy)benzoate] methanesulfonate (FOY), a new antiproteolytic agent, were studied and the following results were obtained. Acute administration of large doses of FOY in conscious dogs and rabbits caused a decrease in spontaneous motility, ataxia, cyanosis, collapse, mydriasis, and respiratory paralysis. The agent had no effect on the central nervous system and exhibited hypotensive effects in dogs in doses of more than 1 mg/kg. Hypotensive responses were not inhibited by treatment with atropine or hexamethonium. FOY had no effects on ECG in the rabbit at doses of less than 30 mg/kg and at doses from 10(-6) to 10(-4)g/ml, distinctly reduced the amplitude of the spontaneous and rhythmic contractions of the isolated rabbit ileum, guinea-pig ileum and rat uterus preparation. The contractile response to nerve stimulation, noradrenaline and barium was suppressed in isolated guinea-pig vas deferens. FOY had no effects on the twitch response of gastrocnemius muscle to sciatic nerve stimulation in rats. The drug caused local irritant effects in rabbits and rats."}
{"id": "PMID:239890", "title": "The activator of cerebroside sulphatase. Purification from human liver and identification as a protein.", "content": "1) A heat-stable activator of human sulphatase A (cerebroside sulphatase) was purified from human liver. It is required for the enzymatic degradation of cerebroside sulphates (sulphatides) in buffers (ionic strength greater than or equal 0.2) with osmolarity in the physiological range. 2) The purification steps involve extraction, acetone precipitation, heat treatment, isoelectric focusing and gel filtration. 3) Based on the definition of a specific activator unit, the purification of the final preparation was approximately 2000-fold over the acetone precipitation and several thousand-fold in the overall procedure. 4) The purified activator migrated as a single protein band when subjected to gel electrophoresis. Its effect was abolished after treatement with pronase E. The apparent molecular weight as determined by gel filtration was 21 500 +/- 1500; the isoelectric point was 4.3. 5) The activating effect of this protein factor and of taurodeoxycholate on cerebroside sulphatase activity was compared on a weight and molar basis.", "contents": "The activator of cerebroside sulphatase. Purification from human liver and identification as a protein. 1) A heat-stable activator of human sulphatase A (cerebroside sulphatase) was purified from human liver. It is required for the enzymatic degradation of cerebroside sulphates (sulphatides) in buffers (ionic strength greater than or equal 0.2) with osmolarity in the physiological range. 2) The purification steps involve extraction, acetone precipitation, heat treatment, isoelectric focusing and gel filtration. 3) Based on the definition of a specific activator unit, the purification of the final preparation was approximately 2000-fold over the acetone precipitation and several thousand-fold in the overall procedure. 4) The purified activator migrated as a single protein band when subjected to gel electrophoresis. Its effect was abolished after treatement with pronase E. The apparent molecular weight as determined by gel filtration was 21 500 +/- 1500; the isoelectric point was 4.3. 5) The activating effect of this protein factor and of taurodeoxycholate on cerebroside sulphatase activity was compared on a weight and molar basis."}
{"id": "PMID:239907", "title": "Clinical and physiological assessment of chlorazepate, diazepam and placebo in anxious neurotics.", "content": "A 28-day double-blind assessment of chlorazepate dipotassium, diazepam and placebo was done on 30 outpatient neurotics with a primary symptom of anxiety. Acute, sub-acute and more chronic effects of the drug were assessed after 3 hours, 14 days and 28 days of drug administration. A battery of psychiatric ratings as well as physiological and psychophysiological assessments were done at each period. The psychometric assessments showed a trend for diazepam to be the most anxiolytic of the three drugs, followed by chlorazepate and then placebo. These measurements did not reach uniform statistically significant differences. Psychological measurements demonstrated the same trends, but some of these reached statistically significant levels. These parameters also indicate a slightly different mode of action of the two drugs at equimolecular doses. Diazepam would depress baseline and stimulation arousal, whereas chlorazepate would decrease baseline CNS arousal, but facilitate CNS response upon stimulation.", "contents": "Clinical and physiological assessment of chlorazepate, diazepam and placebo in anxious neurotics. A 28-day double-blind assessment of chlorazepate dipotassium, diazepam and placebo was done on 30 outpatient neurotics with a primary symptom of anxiety. Acute, sub-acute and more chronic effects of the drug were assessed after 3 hours, 14 days and 28 days of drug administration. A battery of psychiatric ratings as well as physiological and psychophysiological assessments were done at each period. The psychometric assessments showed a trend for diazepam to be the most anxiolytic of the three drugs, followed by chlorazepate and then placebo. These measurements did not reach uniform statistically significant differences. Psychological measurements demonstrated the same trends, but some of these reached statistically significant levels. These parameters also indicate a slightly different mode of action of the two drugs at equimolecular doses. Diazepam would depress baseline and stimulation arousal, whereas chlorazepate would decrease baseline CNS arousal, but facilitate CNS response upon stimulation."}
{"id": "PMID:239908", "title": "Amantadine in drug-induced extrapyramidal signs: a comparative study.", "content": "In our non-blind comparative study, amantadine was as effective as the standard medications, benztropine and ethopropazine, in controlling drug-induced extrapyramidal signs. However, statistically significant improvement was noted a week after all the three medications. In addition, extrapyramidal signs were not completely controlled in most patients even after weeks, even though substantial improvement was noted. This indicates the limitations of the currently available antiparkinsonian medications. Amantadine produced least side effects. Therefore, it may be particulary useful in patients who may not tolerate antiparkinsonian medication with anticholinergic properties. Our clinical finding that two patients with depression improved was rather interesting and needs further exploration. In summary, anamtadine is a valuable addition to our armamentarium of antiparkinsonian drugs. The drug compared favourably with other standard medications. The problem of dissipation of the therapeutic effects over time was not studied in our trial.", "contents": "Amantadine in drug-induced extrapyramidal signs: a comparative study. In our non-blind comparative study, amantadine was as effective as the standard medications, benztropine and ethopropazine, in controlling drug-induced extrapyramidal signs. However, statistically significant improvement was noted a week after all the three medications. In addition, extrapyramidal signs were not completely controlled in most patients even after weeks, even though substantial improvement was noted. This indicates the limitations of the currently available antiparkinsonian medications. Amantadine produced least side effects. Therefore, it may be particulary useful in patients who may not tolerate antiparkinsonian medication with anticholinergic properties. Our clinical finding that two patients with depression improved was rather interesting and needs further exploration. In summary, anamtadine is a valuable addition to our armamentarium of antiparkinsonian drugs. The drug compared favourably with other standard medications. The problem of dissipation of the therapeutic effects over time was not studied in our trial."}
{"id": "PMID:239905", "title": "Spasmolytic activity of two synthetic anilide local anaesthetics.", "content": "Two basic anilides EA-7 and EA-8 were investigated for their antispasmodic activity against a variety of spasmogens on different tissues from different species of animals and comparison was made with lignocaine. EA-8 was found to be the most potent in this respect, followed by EA-7 and lignocaine. The antispasmodic potency does not correspond to their local anaesthetic potency. This suggests a direct depressant effect on tissues.", "contents": "Spasmolytic activity of two synthetic anilide local anaesthetics. Two basic anilides EA-7 and EA-8 were investigated for their antispasmodic activity against a variety of spasmogens on different tissues from different species of animals and comparison was made with lignocaine. EA-8 was found to be the most potent in this respect, followed by EA-7 and lignocaine. The antispasmodic potency does not correspond to their local anaesthetic potency. This suggests a direct depressant effect on tissues."}
{"id": "PMID:239911", "title": "Study by PMR spectroscopy and gel chromatography of the unfolding of substituted kerateines in 8 M urea.", "content": "Various S-substituted derivatives of the reduced low sulphur and high proteins from wool have been prepared in which the substituted group is hydrogen, carboxymethyl, carboxethyl, methyl, carbamidomethyl, cyanoethyl and aminoethyl. The proton magnetic resonance (PMR) spectra and gel filtration chromatography of these proteins have been examined in 8 M urea solution as a function of pH in order to determine conditions under which the proteins occur as random coils in solution with no evidence for the occurrence of non-covalent interactions. The PMR method described in an earlier paper (1) provides an easier and much more sensitive method for the observation of non-covalent interactions in random coil proteins than does the measurement of elution volumes in gel chromatography. The results obtained by both methods are consistent and show that the widest range of pH for which unfolding occurs in 8 M urea is obtained with the S-carboxymethyl, S-carboxyethyl, S-methyl and S-carbamidomethyl derivatives.", "contents": "Study by PMR spectroscopy and gel chromatography of the unfolding of substituted kerateines in 8 M urea. Various S-substituted derivatives of the reduced low sulphur and high proteins from wool have been prepared in which the substituted group is hydrogen, carboxymethyl, carboxethyl, methyl, carbamidomethyl, cyanoethyl and aminoethyl. The proton magnetic resonance (PMR) spectra and gel filtration chromatography of these proteins have been examined in 8 M urea solution as a function of pH in order to determine conditions under which the proteins occur as random coils in solution with no evidence for the occurrence of non-covalent interactions. The PMR method described in an earlier paper (1) provides an easier and much more sensitive method for the observation of non-covalent interactions in random coil proteins than does the measurement of elution volumes in gel chromatography. The results obtained by both methods are consistent and show that the widest range of pH for which unfolding occurs in 8 M urea is obtained with the S-carboxymethyl, S-carboxyethyl, S-methyl and S-carbamidomethyl derivatives."}
{"id": "PMID:239912", "title": "Properties and immunochemical reactivities of carboxy-modified human serum albumin.", "content": "Seven carboxy modified and four amino modified derivatives of human serum albumin have been prepared and studied by optical rotatory dispersion measurements, gel filtration, immunoelectrophoresis, immunodiffusion and by use of an ammonium sulphate technique. It is found that carboxy groups are of major importance for the maintenance of the structure and function of human serum albumin, and that carboxy modification has a much more profound effect than amino modification has to the same relative extent.", "contents": "Properties and immunochemical reactivities of carboxy-modified human serum albumin. Seven carboxy modified and four amino modified derivatives of human serum albumin have been prepared and studied by optical rotatory dispersion measurements, gel filtration, immunoelectrophoresis, immunodiffusion and by use of an ammonium sulphate technique. It is found that carboxy groups are of major importance for the maintenance of the structure and function of human serum albumin, and that carboxy modification has a much more profound effect than amino modification has to the same relative extent."}
{"id": "PMID:239913", "title": "The role of testicular conflicts in a countertransference reaction.", "content": "A case is presented in which a patient's presenting symptoms of impotence and a pervasive inhibition of productivity are dynamically related to a cryptorchild condition which was discovered and treated during childhood. The importance of the cryptorchid condition and its relationship to the patient's later psychopathology are examined. However, it is the therapist's reaction to the clinical material that is the paricular focus of his paper. The therapist obtained the history of cryptorchism in the fifth month of treatment, and then subsequently repressed this data. In addition, a persistent countertransference reaction developed that threatened to disrupt the treatment relationship. In reviewing the course of the therapy, it was possible to determine that the therapist's repression of the patient's cryptorchism and his subsequent countertransference response were directly related to his own repressed testicular conflicts. The implications regarding the existence of similar conflicts in other therapists are discussed.", "contents": "The role of testicular conflicts in a countertransference reaction. A case is presented in which a patient's presenting symptoms of impotence and a pervasive inhibition of productivity are dynamically related to a cryptorchild condition which was discovered and treated during childhood. The importance of the cryptorchid condition and its relationship to the patient's later psychopathology are examined. However, it is the therapist's reaction to the clinical material that is the paricular focus of his paper. The therapist obtained the history of cryptorchism in the fifth month of treatment, and then subsequently repressed this data. In addition, a persistent countertransference reaction developed that threatened to disrupt the treatment relationship. In reviewing the course of the therapy, it was possible to determine that the therapist's repression of the patient's cryptorchism and his subsequent countertransference response were directly related to his own repressed testicular conflicts. The implications regarding the existence of similar conflicts in other therapists are discussed."}
{"id": "PMID:239914", "title": "Local graft versus host reactions within the anterior chamber of the eye: the formation of corneal endothelial pocks.", "content": "Introduction into the rabbit's anterior chamber of lymphoid cells sensitized to the histocompatibility antigens of the recipient leads to the development of an intraocular graft versus host reaction. This takes the form of a more-or-less severe uveitis, and the production of small focal areas of endothelial cell destruction on the posterior surface of the cornea. In the milder responses, these present as discrete pocks on the endothelial layer, which heal rapidly. In the more severe reactions, the foci of endothelial destruction may be so numerous as to overlap, resulting in complete immunologic destruction of the entire endothelium. The dose-response relationships in this experimental system are discussed, as are its uses as a model for the study of the mechanism of endothelial damage during the course of specific corneal graft rejection.", "contents": "Local graft versus host reactions within the anterior chamber of the eye: the formation of corneal endothelial pocks. Introduction into the rabbit's anterior chamber of lymphoid cells sensitized to the histocompatibility antigens of the recipient leads to the development of an intraocular graft versus host reaction. This takes the form of a more-or-less severe uveitis, and the production of small focal areas of endothelial cell destruction on the posterior surface of the cornea. In the milder responses, these present as discrete pocks on the endothelial layer, which heal rapidly. In the more severe reactions, the foci of endothelial destruction may be so numerous as to overlap, resulting in complete immunologic destruction of the entire endothelium. The dose-response relationships in this experimental system are discussed, as are its uses as a model for the study of the mechanism of endothelial damage during the course of specific corneal graft rejection."}
{"id": "PMID:239916", "title": "Prenatal metachromatic leukodystrophy.", "content": "In a family with a metachromatic leukodystrophy patient, two further pregnancies at risk were monitored by amnion cell culture. In one case, a normal baby was predicted and born. In the other case, a prenatal deficiency of arylsulfatase A was found. The diagnosis of metachromatic leukodystrophy was confirmed biochemically in various organs of the fetus by the deficiency of arylsulfatase A. The residual enzyme activity was shown to have an abnormal pH optimum and an increased heat stability. Ultrastructural studies revealed lipid storage in the myelinating nervous system and in the liver. For the interpretation of morphological results, it was indispensable to analyze an age-matched control fetus.", "contents": "Prenatal metachromatic leukodystrophy. In a family with a metachromatic leukodystrophy patient, two further pregnancies at risk were monitored by amnion cell culture. In one case, a normal baby was predicted and born. In the other case, a prenatal deficiency of arylsulfatase A was found. The diagnosis of metachromatic leukodystrophy was confirmed biochemically in various organs of the fetus by the deficiency of arylsulfatase A. The residual enzyme activity was shown to have an abnormal pH optimum and an increased heat stability. Ultrastructural studies revealed lipid storage in the myelinating nervous system and in the liver. For the interpretation of morphological results, it was indispensable to analyze an age-matched control fetus."}
{"id": "PMID:239917", "title": "Comparative inhibitory activity of BL-S640 and two other cephalosporins.", "content": "In vitro antibacterial activity of BL-S640 was compared to that of cephalothin and cephalexin against Gram-negative and Gram-positive bacteria isolated from clinical specimens. BL-S640 demonstrated the best activity on nearly all microbial species studied, except for Haemophilus influenzae and Diplococcus pneumoniae against which cephalothin was slightly more active.", "contents": "Comparative inhibitory activity of BL-S640 and two other cephalosporins. In vitro antibacterial activity of BL-S640 was compared to that of cephalothin and cephalexin against Gram-negative and Gram-positive bacteria isolated from clinical specimens. BL-S640 demonstrated the best activity on nearly all microbial species studied, except for Haemophilus influenzae and Diplococcus pneumoniae against which cephalothin was slightly more active."}
{"id": "PMID:239918", "title": "Semiautomated analysis of ergonovine maleate or methylergonovine maleate tablets and injections by colorimetric or fluorometric systems.", "content": "Two semiautomated analytical systems have been developed to determine ergonovine and methylergonovine maleate in single tablets and injections. The active ingredient is dissolved in a tartrate buffer. In the fluorometric method the stream is automatically diluted with tartrate buffer and excited with ultraviolet light; the resulting fluorescence is measured and recorded. In the colorimetric method, the stream is automatically made basic with sodium hydroxide and extracted with n-butanol. The extract is mixed with p-dimethylaminobenzaldehyde reagent. After reaction, the solution is mixed with sodium nitrite solution, and the developed color is measured at 550 nm. Recoveries of 100% were obtained from spiked placebos. Standard deviations for powdered tablet and injection samples ranged from 0.63 to 1.24%. Comparisons with the USP XVIII methods are presented.", "contents": "Semiautomated analysis of ergonovine maleate or methylergonovine maleate tablets and injections by colorimetric or fluorometric systems. Two semiautomated analytical systems have been developed to determine ergonovine and methylergonovine maleate in single tablets and injections. The active ingredient is dissolved in a tartrate buffer. In the fluorometric method the stream is automatically diluted with tartrate buffer and excited with ultraviolet light; the resulting fluorescence is measured and recorded. In the colorimetric method, the stream is automatically made basic with sodium hydroxide and extracted with n-butanol. The extract is mixed with p-dimethylaminobenzaldehyde reagent. After reaction, the solution is mixed with sodium nitrite solution, and the developed color is measured at 550 nm. Recoveries of 100% were obtained from spiked placebos. Standard deviations for powdered tablet and injection samples ranged from 0.63 to 1.24%. Comparisons with the USP XVIII methods are presented."}
{"id": "PMID:239915", "title": "Human erythrocyte glucose 6-phosphate dehydrogenase. Influence of coenzyme derivatives on thermostability and kinetic properties.", "content": "A number of derivatives of NADP(H) were tested with respect to their effectiveness in interacting with tetrameric glucose 6-phosphate dehydrogenase (G6PD) retaining only the fraction of \"structural\" coenzyme (4 moles NADP). Interaction was probed by two parameters: a) increased thermostability of G6PD activity, measured as the difference in the corresponding transition temperature (Tm) of samples containing and lacking the NADP derivatives, respectively; b) competitive inhibition toward NADP, expressed a Ki values. Protection afforded by the various effectors against thermal denaturation decreased in the following order: NADPH, NADP, PADP-ribose, adenosine 2',5'-P2. Other NADP derivatives, including 2',3' cyclic NADP, NMN, NMNH, nicotinamide, adenosine 2'-P, were uneffective in respect to this property. The kinetically measured affinity was the greatest for NADPH and decreased progressively for the following effectors: PADP-ribose, NADP, NMNH, PADP-glycolaldehyde, adenosine 2',5'-P2, PADP-ribitol, adenosine 2'-P. Nicotinamide and NMN were uneffective on NADP binding. These data show that the adenosine moiety of NADP is more critically involved than the nicotinamide portion in the interaction with human G6PD.", "contents": "Human erythrocyte glucose 6-phosphate dehydrogenase. Influence of coenzyme derivatives on thermostability and kinetic properties. A number of derivatives of NADP(H) were tested with respect to their effectiveness in interacting with tetrameric glucose 6-phosphate dehydrogenase (G6PD) retaining only the fraction of \"structural\" coenzyme (4 moles NADP). Interaction was probed by two parameters: a) increased thermostability of G6PD activity, measured as the difference in the corresponding transition temperature (Tm) of samples containing and lacking the NADP derivatives, respectively; b) competitive inhibition toward NADP, expressed a Ki values. Protection afforded by the various effectors against thermal denaturation decreased in the following order: NADPH, NADP, PADP-ribose, adenosine 2',5'-P2. Other NADP derivatives, including 2',3' cyclic NADP, NMN, NMNH, nicotinamide, adenosine 2'-P, were uneffective in respect to this property. The kinetically measured affinity was the greatest for NADPH and decreased progressively for the following effectors: PADP-ribose, NADP, NMNH, PADP-glycolaldehyde, adenosine 2',5'-P2, PADP-ribitol, adenosine 2'-P. Nicotinamide and NMN were uneffective on NADP binding. These data show that the adenosine moiety of NADP is more critically involved than the nicotinamide portion in the interaction with human G6PD."}
{"id": "PMID:239919", "title": "Soluble and membrane-bound aspartate-binding activities in Salmonella typhimurium.", "content": "The specificities of the soluble and membrane aspartate-binding activities were compared with each other and with the specificity of aspartate chemotaxis and were found to be distinct. The soluble aspartate-binding protein was purified to homogeneity and had a molecular weight of 30,000. The dissociation constant was 10(-6) M for aspartate, and the protein bound glutamate, cysteic acid, and 2-amino-3-phosphonopropionate. Aspartate transport was inhibited by cysteic acid.", "contents": "Soluble and membrane-bound aspartate-binding activities in Salmonella typhimurium. The specificities of the soluble and membrane aspartate-binding activities were compared with each other and with the specificity of aspartate chemotaxis and were found to be distinct. The soluble aspartate-binding protein was purified to homogeneity and had a molecular weight of 30,000. The dissociation constant was 10(-6) M for aspartate, and the protein bound glutamate, cysteic acid, and 2-amino-3-phosphonopropionate. Aspartate transport was inhibited by cysteic acid."}
{"id": "PMID:239920", "title": "Regulation of breakdown and synthesis of L-glutamate decarboxylase in Clostridium perfringens.", "content": "L-Glutamate decarboxylase (GAD) activity of Clostridium perfringens (ATCC 8009) cells grown in various culture conditions was investigated. Remarkable variations of GAD level occur during the growth cycle in thioglycollate broth. These changes are affected by the pH of the culture medium. Addition of alkali to the culture media results in decrease of cell GAD activity, whereas increase of enzyme level occurs only in cells growing in unbuffered media. The results indicate that the mechanism regulating the GAD levels is sensitive to the changes of pH (or buffering substances) rather than to the steady pH values. Neither repression by glucose nor induction by L-glutamate was observed. Moreover, high concentrations of the free amino acid substrate in the culture media considerably decrease cell GAD activity, owing to the buffering effect of the amino acid. The molecular mechanism supporting the variations of GAD activity during the growth cycle of the cells were investigated and tentatively related to the structural and functional properties of the pure enzyme. It is shown that the drop of GAD activity during the lag phase is due to protein breakdown. Evidence is presented suggesting a control of protein degradation by its quaternary structure. Data are also reported supporting de novo synthesis of GAD during the late logarithmic phase of cell growth. Finally, the possible role of GAD as part of the pH regulation system of C. perfringens cells is discussed in relation both to physiologic conditions of the bacterial cell and to the molecular mechanisms regulating the GAD activity in vivo.", "contents": "Regulation of breakdown and synthesis of L-glutamate decarboxylase in Clostridium perfringens. L-Glutamate decarboxylase (GAD) activity of Clostridium perfringens (ATCC 8009) cells grown in various culture conditions was investigated. Remarkable variations of GAD level occur during the growth cycle in thioglycollate broth. These changes are affected by the pH of the culture medium. Addition of alkali to the culture media results in decrease of cell GAD activity, whereas increase of enzyme level occurs only in cells growing in unbuffered media. The results indicate that the mechanism regulating the GAD levels is sensitive to the changes of pH (or buffering substances) rather than to the steady pH values. Neither repression by glucose nor induction by L-glutamate was observed. Moreover, high concentrations of the free amino acid substrate in the culture media considerably decrease cell GAD activity, owing to the buffering effect of the amino acid. The molecular mechanism supporting the variations of GAD activity during the growth cycle of the cells were investigated and tentatively related to the structural and functional properties of the pure enzyme. It is shown that the drop of GAD activity during the lag phase is due to protein breakdown. Evidence is presented suggesting a control of protein degradation by its quaternary structure. Data are also reported supporting de novo synthesis of GAD during the late logarithmic phase of cell growth. Finally, the possible role of GAD as part of the pH regulation system of C. perfringens cells is discussed in relation both to physiologic conditions of the bacterial cell and to the molecular mechanisms regulating the GAD activity in vivo."}
{"id": "PMID:239921", "title": "Physiological and biochemical role of the butanediol pathway in Aerobacter (Enterobacter) aerogenes.", "content": "Aerobacter (Enterobacter) aerogenes wild type and three mutants deficient in the formation of acetoin and 2,3-butanediol were grown in a glucose minimal medium. Culture densities, pH, and diacetyl, acetoin, and 2,3-butanediol levels were recorded. The pH in wild-type cultures dropped from 7.0 to 5.8, remained constant while acetoin and 2,3-butanediol were formed, and increased to pH 6.5 after exhaustion of the carbon source. More 2,3-butanediol than acetoin was formed initially, but after glucose exhaustion reoxidation to acetoin occurred. The three mutants differed from the wild type in yielding acid cultures (pH below 4.5). The wild type and one of the mutants were grown exponentially under aerobic and anaerobic conditions with the pH fixed at 7.0, 5.8, and 5.0, respectively. Growth rates decreased with decreasing pH values. Aerobically, this effect was weak, and the two strains were affected to the same degree. Under anaerobic conditions, the growth rates were markedly inhibited at a low pH, and the mutant was slightly more affected than the wild type. Levels of alcohol dehydrogenase were low under all conditions, indicating that the enzyme plays no role during exponential growth. The levels of diacetyl (acetoin) reductase, lactate dehydrogenase, and phosphotransacetylase were independent of the pH during aerobic growth of the two strains. Under anaerobic conditions, the formation of diacetyl (acetoin) reductase was pH dependent, with much higher levels of the enzyme at pH 5.0 than at pH 7.0. Lactate dehydrogenase and phosphotransacetylase revealed the same pattern of pH-dependent formation in the mutant, but not in the wild type.", "contents": "Physiological and biochemical role of the butanediol pathway in Aerobacter (Enterobacter) aerogenes. Aerobacter (Enterobacter) aerogenes wild type and three mutants deficient in the formation of acetoin and 2,3-butanediol were grown in a glucose minimal medium. Culture densities, pH, and diacetyl, acetoin, and 2,3-butanediol levels were recorded. The pH in wild-type cultures dropped from 7.0 to 5.8, remained constant while acetoin and 2,3-butanediol were formed, and increased to pH 6.5 after exhaustion of the carbon source. More 2,3-butanediol than acetoin was formed initially, but after glucose exhaustion reoxidation to acetoin occurred. The three mutants differed from the wild type in yielding acid cultures (pH below 4.5). The wild type and one of the mutants were grown exponentially under aerobic and anaerobic conditions with the pH fixed at 7.0, 5.8, and 5.0, respectively. Growth rates decreased with decreasing pH values. Aerobically, this effect was weak, and the two strains were affected to the same degree. Under anaerobic conditions, the growth rates were markedly inhibited at a low pH, and the mutant was slightly more affected than the wild type. Levels of alcohol dehydrogenase were low under all conditions, indicating that the enzyme plays no role during exponential growth. The levels of diacetyl (acetoin) reductase, lactate dehydrogenase, and phosphotransacetylase were independent of the pH during aerobic growth of the two strains. Under anaerobic conditions, the formation of diacetyl (acetoin) reductase was pH dependent, with much higher levels of the enzyme at pH 5.0 than at pH 7.0. Lactate dehydrogenase and phosphotransacetylase revealed the same pattern of pH-dependent formation in the mutant, but not in the wild type."}
{"id": "PMID:239922", "title": "p-Aminobenzoate-p-aminobenzoate.", "content": "p-Aminobenzoate (PABA) synthase from Bacillus subtilis is an aggregate composed of two nonidentical subunits and has the following properties. (i) In crude extracts this enzyme catalyzes the formation of PABA in the presence of chorismate and either glutamine (amidotransferase) or ammonia (aminase). The amidotransferase activity is about 5- to 10-fold higher than the aminase activity and is stable for at least 1 week when frozen at -70 C. (II) Although no divalent cation requirement could be demonstrated with crude extracts, 2 mM ethylene-diaminetetraacetic acid completely inhibits both activities. (iii) After ammonium sulfate fractionation both the aminase and amidotransferase activities require Mg2+ and guanosine in addition to the substrates indicated above for optimal activity. The guanosine requirement can be replaced by guanosine 5'-monophosphate, guanosine 5'-diphosphate, and guanosine 5'-triphosphate but not by guanine, adenosine 5'-triphosphate, uridine 5'-triphosphate, cytidine 5'-triphosphate, thymidine 5'-triphosphate, inorganic phosphate, and phosphoribosylpyrophosphate. Furthermore, at a pH above 7.4 or below 6.4 activity is rapidly lost a 4 C, or -60 C. (IV) The enzyme is composed of two non-identical subunits, designated subunit A and subunit X. Subunit A has an estimated molecular weight of 31,000, whereas subunit X has an estimated molecular weight of 19,000. Subunit A has aminase activity but no amidotransferase activity; a mutation at the pabA locus results in the loss of PABA synthase activity. Subunit X, which is also a component of the anthranilate synthase complex, has no PABA synthase activity itself but complexes with subunit A to give an AX aggregate that can use glutamine as a substrate. (v) The molecular weight of the AX complex has been estimated at 50,000, suggesting a 1:1 ratio of subunits. (vi) The enzyme is readily associated and dissociated.", "contents": "p-Aminobenzoate-p-aminobenzoate. p-Aminobenzoate (PABA) synthase from Bacillus subtilis is an aggregate composed of two nonidentical subunits and has the following properties. (i) In crude extracts this enzyme catalyzes the formation of PABA in the presence of chorismate and either glutamine (amidotransferase) or ammonia (aminase). The amidotransferase activity is about 5- to 10-fold higher than the aminase activity and is stable for at least 1 week when frozen at -70 C. (II) Although no divalent cation requirement could be demonstrated with crude extracts, 2 mM ethylene-diaminetetraacetic acid completely inhibits both activities. (iii) After ammonium sulfate fractionation both the aminase and amidotransferase activities require Mg2+ and guanosine in addition to the substrates indicated above for optimal activity. The guanosine requirement can be replaced by guanosine 5'-monophosphate, guanosine 5'-diphosphate, and guanosine 5'-triphosphate but not by guanine, adenosine 5'-triphosphate, uridine 5'-triphosphate, cytidine 5'-triphosphate, thymidine 5'-triphosphate, inorganic phosphate, and phosphoribosylpyrophosphate. Furthermore, at a pH above 7.4 or below 6.4 activity is rapidly lost a 4 C, or -60 C. (IV) The enzyme is composed of two non-identical subunits, designated subunit A and subunit X. Subunit A has an estimated molecular weight of 31,000, whereas subunit X has an estimated molecular weight of 19,000. Subunit A has aminase activity but no amidotransferase activity; a mutation at the pabA locus results in the loss of PABA synthase activity. Subunit X, which is also a component of the anthranilate synthase complex, has no PABA synthase activity itself but complexes with subunit A to give an AX aggregate that can use glutamine as a substrate. (v) The molecular weight of the AX complex has been estimated at 50,000, suggesting a 1:1 ratio of subunits. (vi) The enzyme is readily associated and dissociated."}
{"id": "PMID:239923", "title": "Localization of acid phosphatase in protoplasts from Saccharomyces cerevisiae.", "content": "The localization of acid phosphatase (EC 3.1.3.2) in secreting protoplasts prepared from Saccharomyces cerevisiae is reported for the first time. Using a Gomori technique we were able to show acid phosphatase at those organelles in the protoplasts which are generally involved in the processes of biosynthesis and secretion of glycoproteins in eukaryotic cells.", "contents": "Localization of acid phosphatase in protoplasts from Saccharomyces cerevisiae. The localization of acid phosphatase (EC 3.1.3.2) in secreting protoplasts prepared from Saccharomyces cerevisiae is reported for the first time. Using a Gomori technique we were able to show acid phosphatase at those organelles in the protoplasts which are generally involved in the processes of biosynthesis and secretion of glycoproteins in eukaryotic cells."}
{"id": "PMID:239924", "title": "Derepressed levels of glutamate synthase and glutamine synthetase in Escherichia coli mutants altered in glutamyl-transfer ribonucleic acid synthetase.", "content": "The levels of glutamate synthase and of glutamine synthetase are both derepressed 10-fold in strain JP1449 of Escherichia coli carrying a thermosensitive mutation in the glutamyl-transfer ribonucleic acid (tRNA) synthetase and growing exponentially but at a reduced rate at a partially restrictive temperature, compared with the levels in strain AB347 isogenic with strain JP1449 except for this thermosensitive mutation and the marker aro. These two enzymes catalyze one of the two pathways for glutamate biosynthesis in E. coli, the other being defined by the glutamate dehydrogenase. We observed a correlation between the percentage of charged tRNAGlu and the level of glutamate synthase in various mutants reported to have an altered glutamyl-tRNA synthetase activity. These results suggest that a glutamyl-tRNA might be involved in the repression of the biosynthesis of the glutamate synthase and of the glutamine synthetase and would couple the regulation of the biosynthesis of these two enzymes, which can work in tandem to synthesize glutamate when the ammonia concentration is low in E. coli but whose structural genes are quite distant from each other. No derepression of the level of the glutamate dehydrogenase was observed in mutant strain JP1449 under the conditions where the levels of the glutamine synthetase and of the glutamate synthase were derepressed. This result indicates that the two pathways for glutamate biosynthesis in E. coli are under different regulatory controls. The glutamate has been reported to be probably the key regulatory element of the biosynthesis of the glutamate dehydrogenase. Our results indicate that the cell has chosen the level of glutamyl-tRNA as a more sensitive probe to regulate the biosynthesis of the enzymes of the other pathway, which must be energized at a low ammonia concentration.", "contents": "Derepressed levels of glutamate synthase and glutamine synthetase in Escherichia coli mutants altered in glutamyl-transfer ribonucleic acid synthetase. The levels of glutamate synthase and of glutamine synthetase are both derepressed 10-fold in strain JP1449 of Escherichia coli carrying a thermosensitive mutation in the glutamyl-transfer ribonucleic acid (tRNA) synthetase and growing exponentially but at a reduced rate at a partially restrictive temperature, compared with the levels in strain AB347 isogenic with strain JP1449 except for this thermosensitive mutation and the marker aro. These two enzymes catalyze one of the two pathways for glutamate biosynthesis in E. coli, the other being defined by the glutamate dehydrogenase. We observed a correlation between the percentage of charged tRNAGlu and the level of glutamate synthase in various mutants reported to have an altered glutamyl-tRNA synthetase activity. These results suggest that a glutamyl-tRNA might be involved in the repression of the biosynthesis of the glutamate synthase and of the glutamine synthetase and would couple the regulation of the biosynthesis of these two enzymes, which can work in tandem to synthesize glutamate when the ammonia concentration is low in E. coli but whose structural genes are quite distant from each other. No derepression of the level of the glutamate dehydrogenase was observed in mutant strain JP1449 under the conditions where the levels of the glutamine synthetase and of the glutamate synthase were derepressed. This result indicates that the two pathways for glutamate biosynthesis in E. coli are under different regulatory controls. The glutamate has been reported to be probably the key regulatory element of the biosynthesis of the glutamate dehydrogenase. Our results indicate that the cell has chosen the level of glutamyl-tRNA as a more sensitive probe to regulate the biosynthesis of the enzymes of the other pathway, which must be energized at a low ammonia concentration."}
{"id": "PMID:239925", "title": "L-asparagine uptake in Escherichia coli.", "content": "The uptake of L-asparagine by Escherichia coli K-12 is characterized by two kinetic components with apparent Km values of 3.5 muM and 80 muM. The 3.5 muM Km system displays a maximum velocity of 1.1 nmol/min per mg of protein, which is a low value when compared with derepressed levels of other amino acid transport systems but is relatively specific for L-asparagine. Compounds providing effective competition for L-asparagine uptake were 4-carbon analogues of the L-isomer with alterations at the beta-amide position, i.e., 5-diazo-4-oxo-L-norvaline (Ki = 4.6 muM), beta-hydroxyamyl-L-aspartic acid (Ki = 10 muM), and L-aspartic acid (Ki = 50 muM). Asparagine uptake is energy dependent and is inhibited by a number of metabolic inhibitors. In a derived strain of E. coli deficient in cytoplasmic asparaginase activity asparagine can be accumulated several-fold above the apparent biosynthetic pool of the amino acid and 100-fold above the external medium. The high affinity system is repressed by culture of cells with L-asparagine supplements in excess of 1 mM and is suggested to be necessary for growth of E. coli asparagine auxotrophs with lower supplement concentrations.", "contents": "L-asparagine uptake in Escherichia coli. The uptake of L-asparagine by Escherichia coli K-12 is characterized by two kinetic components with apparent Km values of 3.5 muM and 80 muM. The 3.5 muM Km system displays a maximum velocity of 1.1 nmol/min per mg of protein, which is a low value when compared with derepressed levels of other amino acid transport systems but is relatively specific for L-asparagine. Compounds providing effective competition for L-asparagine uptake were 4-carbon analogues of the L-isomer with alterations at the beta-amide position, i.e., 5-diazo-4-oxo-L-norvaline (Ki = 4.6 muM), beta-hydroxyamyl-L-aspartic acid (Ki = 10 muM), and L-aspartic acid (Ki = 50 muM). Asparagine uptake is energy dependent and is inhibited by a number of metabolic inhibitors. In a derived strain of E. coli deficient in cytoplasmic asparaginase activity asparagine can be accumulated several-fold above the apparent biosynthetic pool of the amino acid and 100-fold above the external medium. The high affinity system is repressed by culture of cells with L-asparagine supplements in excess of 1 mM and is suggested to be necessary for growth of E. coli asparagine auxotrophs with lower supplement concentrations."}
{"id": "PMID:239926", "title": "Properties of a membrane-bound cardiolipin synthetase from Lactobacillus plantarum.", "content": "Cardiolipin (CL) synthetase of Lactobacillus plantarum 17-5 catalyzed the stoichiometric conversion of 2 mol of phosphatidylglycerol to 1 mol of CL. The enzyme activity was linear with time for 30 min at 37 C and with protein concentration between 20 and 200 mug of protein per ml. The enzyme was membrane associated, had a pH optimum of 5.1 in phosphate buffer, and was not stimulated by Mg2+, and the activity was not affected by the addition of ethylenediaminetetraacetic acid, cytidine diphosphate diglyceride, or cytidine triphosphate. The reaction was inhibited about 95% by Triton X-100 (0.5% final concentration) and by CL, the end product of the reaction. The activity of this enzyme was studied as a function of growth. The CL synthetase specific activity was highest during the early and midexponential growth phases, as was the cellular content of CL. The results demonstrate a correlation between enzyme-specific activity and lipid content of the cells.", "contents": "Properties of a membrane-bound cardiolipin synthetase from Lactobacillus plantarum. Cardiolipin (CL) synthetase of Lactobacillus plantarum 17-5 catalyzed the stoichiometric conversion of 2 mol of phosphatidylglycerol to 1 mol of CL. The enzyme activity was linear with time for 30 min at 37 C and with protein concentration between 20 and 200 mug of protein per ml. The enzyme was membrane associated, had a pH optimum of 5.1 in phosphate buffer, and was not stimulated by Mg2+, and the activity was not affected by the addition of ethylenediaminetetraacetic acid, cytidine diphosphate diglyceride, or cytidine triphosphate. The reaction was inhibited about 95% by Triton X-100 (0.5% final concentration) and by CL, the end product of the reaction. The activity of this enzyme was studied as a function of growth. The CL synthetase specific activity was highest during the early and midexponential growth phases, as was the cellular content of CL. The results demonstrate a correlation between enzyme-specific activity and lipid content of the cells."}
{"id": "PMID:239927", "title": "Regulation of glutaminase levels in Escherichia coli.", "content": "Nitrogenous metabolites, cyclic adenosine 3':5'-monophosphate (cAMP), and the stage of culture growth all influence the levels of glutaminase A in Escherichia coli, but no variables in culture conditions alter the levels of glutaminase B. Growth of E. coli on culture media containing glucose and excess ammonia results in a rise in the level of glutaminase A as the cultures enter stationary phase; this rise is abolished by ammonia limitation. cAMP or glycerol reduce the level of glutaminase A. In mutants deficient in cAMP receptor protein, glutaminase A levels are unchanged by cAMP, but they are still susceptible to regulation by ammonia. We consider glutaminase B to be a constitutive enzyme, since its levels appear independent of nutritional conditions.", "contents": "Regulation of glutaminase levels in Escherichia coli. Nitrogenous metabolites, cyclic adenosine 3':5'-monophosphate (cAMP), and the stage of culture growth all influence the levels of glutaminase A in Escherichia coli, but no variables in culture conditions alter the levels of glutaminase B. Growth of E. coli on culture media containing glucose and excess ammonia results in a rise in the level of glutaminase A as the cultures enter stationary phase; this rise is abolished by ammonia limitation. cAMP or glycerol reduce the level of glutaminase A. In mutants deficient in cAMP receptor protein, glutaminase A levels are unchanged by cAMP, but they are still susceptible to regulation by ammonia. We consider glutaminase B to be a constitutive enzyme, since its levels appear independent of nutritional conditions."}
{"id": "PMID:239928", "title": "Glucose-forming amylase in human urine.", "content": "This paper describes the isolation and study of glucose-forming amylase existing in human urine as a normal component. After removing alpha-amylase [EC 3.2.1.1] by adsorption onto raw starch, urine was treated with DEAE-cellulose and Bio Gel P-150, and three fractionated proteins (F-1, F-2, and F-3), isolated in a homogeneous state by gel filtration, were shown to display glucose-formine amylase activity. They all hydrolyzed starch and glycogen, releasing glucose as the sole product, and also hydrolyzed maltose. However, their molecular weights, as estimated by gel filtration, isoelectric points, stabilities, and several enzymatic properties were different. The implications of the results are discussed.", "contents": "Glucose-forming amylase in human urine. This paper describes the isolation and study of glucose-forming amylase existing in human urine as a normal component. After removing alpha-amylase [EC 3.2.1.1] by adsorption onto raw starch, urine was treated with DEAE-cellulose and Bio Gel P-150, and three fractionated proteins (F-1, F-2, and F-3), isolated in a homogeneous state by gel filtration, were shown to display glucose-formine amylase activity. They all hydrolyzed starch and glycogen, releasing glucose as the sole product, and also hydrolyzed maltose. However, their molecular weights, as estimated by gel filtration, isoelectric points, stabilities, and several enzymatic properties were different. The implications of the results are discussed."}
{"id": "PMID:239929", "title": "O-acetylserine and O-acetylhomoserine sulfhydrylase of yeast; studies with methionine auxotrophs.", "content": "The nutritional requirements of three yeast mutants, previously shown to possess low O-acetyl-L-serine (OAS) and O-acetyl-L-homoserine (OAH) sulfhydrylase activities, were reinvestigated. It was thus found that one mutant (strain No. 16), previously identified as a homocysteine auxotroph, is in fact a double mutant requiring both cysteine and OAH. In agreement with the previous assignment, the other two strains (strains No. 13 and 17) were shown to be true cysteine auxotrophs. These results can best be explained by assuming the cystathionine pathway to be the main route of homocysteine synthesis in this organism. It was further found that extracts of the three mutants contain genetically modified OAS-OAH sulfhydrylases with much reduced catalytic activities. Modified sulfhydrylase was partially purified from strain No. 16 by the same procedure as for the wild-type enzyme. Both OAS and OAH sulfhydrylase activities of the mutant enzyme were copurified and behaved identically on polyacrylamide gel electrophoresis. The enzymatic and physicochemical properties of the purified mutant enzyme were shown to be very similar to those of the wild-type enzyme, except that the catalytic activities of the former were only 3-5% of those of the latter, and that the ratio of OAH sulfhydrylase to OAS sulfhydrylase activity was somewhat lower in the former than in the latter.", "contents": "O-acetylserine and O-acetylhomoserine sulfhydrylase of yeast; studies with methionine auxotrophs. The nutritional requirements of three yeast mutants, previously shown to possess low O-acetyl-L-serine (OAS) and O-acetyl-L-homoserine (OAH) sulfhydrylase activities, were reinvestigated. It was thus found that one mutant (strain No. 16), previously identified as a homocysteine auxotroph, is in fact a double mutant requiring both cysteine and OAH. In agreement with the previous assignment, the other two strains (strains No. 13 and 17) were shown to be true cysteine auxotrophs. These results can best be explained by assuming the cystathionine pathway to be the main route of homocysteine synthesis in this organism. It was further found that extracts of the three mutants contain genetically modified OAS-OAH sulfhydrylases with much reduced catalytic activities. Modified sulfhydrylase was partially purified from strain No. 16 by the same procedure as for the wild-type enzyme. Both OAS and OAH sulfhydrylase activities of the mutant enzyme were copurified and behaved identically on polyacrylamide gel electrophoresis. The enzymatic and physicochemical properties of the purified mutant enzyme were shown to be very similar to those of the wild-type enzyme, except that the catalytic activities of the former were only 3-5% of those of the latter, and that the ratio of OAH sulfhydrylase to OAS sulfhydrylase activity was somewhat lower in the former than in the latter."}
{"id": "PMID:239930", "title": "Reduced nicotinamide adenine dinucleotide phosphate-dependent lipid peroxidation by beef heart submitochondrial particles.", "content": "Electron transport particles (ETP) prepared from beef heart mitochondria formed malondialdehyde by NADPH-dependent lipid peroixidation in the presence of ferric ions and ADP or ATP. The reaction was inhibited by MnCl2, EDTA, or radical scavengers, but was not inhibited by p-hydroxymercuribenzoate (PHMB) or respiratory chain inhibitors. The oxidation of NADPH and oxygen consumption by ETP were activated by the addition of ferric ions and APT, and inhibited by inhibitors of lipid peroxidation. This peroxidation system was apparently different from those of liver microsomes and mitochondria as regards the effect of PHMB, optimal pH and the concentration of NADPH for half-maximal reaction velocity.", "contents": "Reduced nicotinamide adenine dinucleotide phosphate-dependent lipid peroxidation by beef heart submitochondrial particles. Electron transport particles (ETP) prepared from beef heart mitochondria formed malondialdehyde by NADPH-dependent lipid peroixidation in the presence of ferric ions and ADP or ATP. The reaction was inhibited by MnCl2, EDTA, or radical scavengers, but was not inhibited by p-hydroxymercuribenzoate (PHMB) or respiratory chain inhibitors. The oxidation of NADPH and oxygen consumption by ETP were activated by the addition of ferric ions and APT, and inhibited by inhibitors of lipid peroxidation. This peroxidation system was apparently different from those of liver microsomes and mitochondria as regards the effect of PHMB, optimal pH and the concentration of NADPH for half-maximal reaction velocity."}
{"id": "PMID:239931", "title": "Studies on the state of tyrosyl residues in a ribonuclease from seminal vesicles.", "content": "In order to study the state of tyrosyl residues in a ribouuclease from bovine semina vesicles [EC 3.1.4.22, RNase Vs1] several lines of experiments were carried out. Spectrophotometric titration of RNase Vs1 indicated that two out of 8 tyrosine residues were titrated very easily and their apparent pKa values were about 9.8. Next, about 4 residues were titrated at pH up to 13.5. The remaining 2 residues were titrated time-dependently at pH 13.5. In 8 M urea, about 6 tyrosine residues were titrated with apparent pK4 values of about 11.2 and about 2 residues were titrated time-dependently at pH 13.5. Acetylation of RNase Vs1 with N-acetylimidazole was studied at pH 7.5. In aqueous solution, about 1.1-3.5 tyrosine residues were acetylated, depending on the experimental conditions, and in 8 M urea, 5.3 tyrosine residues were modified. RNase Vs1 was nitrated with tetranitromethane at pH 7.5. In aqueous solution, about 2.5 tyrosine residues were nitrated very easily; the enzymatic activity of the modified enzymes was 130-200% of that of the native enzyme. In 8 M urea, the reactivity of the tyrosine residues increased and about 4-5.5 residues were modified. The results of chemical modification and spectrophotometric titration indicated that about two tyrosine residues in RNase Vs1 were exposed to the solvent and were more reactive to various reagents, and 3-4 tyrosine residues were less reactive. The final 2 residues were not accessible to the reagent even in the presence of urea, but were titraten at pH 13.5. The solvent perturbation difference spectrum using ethylene glycol as a perturbant indicated that about 4 tyrosine residues were perturbed. When the pH of the enzyme solution was changed from 7.0 to 1.0, the change in optical density of RNase Vs1 due to denaturation blue shift was about 1,600 at 287nm. The optical density change at 287 nm of native RNase Vs1 on exposure to 8 M urea and 6 M guanidine-HCl indicated that the environments of 2-3 and 4 tyrosine residues were changed by the addition of the denaturants, urea and guanidine-HCl, respectively. In RNase Vs1 having about four nitrotyrosine residues, the two most inaccessible tyrosine residues remained resistant to titration with alkali. On adding nucleotide, nitrated RNase Vs1 gave a difference spectrum in the ultraviolet region but not in 320-460 nm region, where nitrotyrosine residues absorb light. This may indicate that tyrosine residues located relatively near the surface of the molecule are not perturbed directly by nucleotide binding.", "contents": "Studies on the state of tyrosyl residues in a ribonuclease from seminal vesicles. In order to study the state of tyrosyl residues in a ribouuclease from bovine semina vesicles [EC 3.1.4.22, RNase Vs1] several lines of experiments were carried out. Spectrophotometric titration of RNase Vs1 indicated that two out of 8 tyrosine residues were titrated very easily and their apparent pKa values were about 9.8. Next, about 4 residues were titrated at pH up to 13.5. The remaining 2 residues were titrated time-dependently at pH 13.5. In 8 M urea, about 6 tyrosine residues were titrated with apparent pK4 values of about 11.2 and about 2 residues were titrated time-dependently at pH 13.5. Acetylation of RNase Vs1 with N-acetylimidazole was studied at pH 7.5. In aqueous solution, about 1.1-3.5 tyrosine residues were acetylated, depending on the experimental conditions, and in 8 M urea, 5.3 tyrosine residues were modified. RNase Vs1 was nitrated with tetranitromethane at pH 7.5. In aqueous solution, about 2.5 tyrosine residues were nitrated very easily; the enzymatic activity of the modified enzymes was 130-200% of that of the native enzyme. In 8 M urea, the reactivity of the tyrosine residues increased and about 4-5.5 residues were modified. The results of chemical modification and spectrophotometric titration indicated that about two tyrosine residues in RNase Vs1 were exposed to the solvent and were more reactive to various reagents, and 3-4 tyrosine residues were less reactive. The final 2 residues were not accessible to the reagent even in the presence of urea, but were titraten at pH 13.5. The solvent perturbation difference spectrum using ethylene glycol as a perturbant indicated that about 4 tyrosine residues were perturbed. When the pH of the enzyme solution was changed from 7.0 to 1.0, the change in optical density of RNase Vs1 due to denaturation blue shift was about 1,600 at 287nm. The optical density change at 287 nm of native RNase Vs1 on exposure to 8 M urea and 6 M guanidine-HCl indicated that the environments of 2-3 and 4 tyrosine residues were changed by the addition of the denaturants, urea and guanidine-HCl, respectively. In RNase Vs1 having about four nitrotyrosine residues, the two most inaccessible tyrosine residues remained resistant to titration with alkali. On adding nucleotide, nitrated RNase Vs1 gave a difference spectrum in the ultraviolet region but not in 320-460 nm region, where nitrotyrosine residues absorb light. This may indicate that tyrosine residues located relatively near the surface of the molecule are not perturbed directly by nucleotide binding."}
{"id": "PMID:239932", "title": "Purification and properties of a new ribonuclease from Aspergillus saitoi.", "content": "From a commercial digestive produced from Aspergillus saitoi, a ribonuclease [EC 3.1.4.23] having a molecular weight of 12,500 has been isolated in addition to the RNase reported previously, which had a molecular weight of 38,000. The enzyme was found to be homogeneous by chromatography on DEAE-cellulose, disc electrophoresis on polyacrylamide gel, and ultracentrifugation. The NH2-terminal amino acid was identified as glutamic acid. The amino acid composition indicated the presence of about 13 tyrosyl residues, 3 histidyl residues, and 2 half-cystine residues. The pH optimum of the RNase was 4.5, using RNA as a substrate. The enzyme was stable on heating at 70 degrees for 5 min from pH 2 to 10. It hydrolysed RNA completely to mononucleotides via 2', 3'-cyclic nucleotides. The rates of release of nucleotides and 2', 3'-cyclic nucleotides were in the order: guanylic acid is greater than adenylic acid is greater than cytidylic acid is greater than uridylic acid.", "contents": "Purification and properties of a new ribonuclease from Aspergillus saitoi. From a commercial digestive produced from Aspergillus saitoi, a ribonuclease [EC 3.1.4.23] having a molecular weight of 12,500 has been isolated in addition to the RNase reported previously, which had a molecular weight of 38,000. The enzyme was found to be homogeneous by chromatography on DEAE-cellulose, disc electrophoresis on polyacrylamide gel, and ultracentrifugation. The NH2-terminal amino acid was identified as glutamic acid. The amino acid composition indicated the presence of about 13 tyrosyl residues, 3 histidyl residues, and 2 half-cystine residues. The pH optimum of the RNase was 4.5, using RNA as a substrate. The enzyme was stable on heating at 70 degrees for 5 min from pH 2 to 10. It hydrolysed RNA completely to mononucleotides via 2', 3'-cyclic nucleotides. The rates of release of nucleotides and 2', 3'-cyclic nucleotides were in the order: guanylic acid is greater than adenylic acid is greater than cytidylic acid is greater than uridylic acid."}
{"id": "PMID:239933", "title": "Change in effective pH of salt solutions on freezing, as evidenced by altered reactivities of heme alpha towards carbonyl reagents.", "content": "Addition of NaHSO3 or HCN to the formyl group of heme alpha was greatly accelerated by freezing reaction mixtures prepared in aq. Na2CO3, and freezing resulted in characteristic color and spectral changes of the solutions. Similar changes were observed on decreasing the pH of alkaline reaction mixtures with HCl at room temperature, indicating that the effective pH of certain salt solutions is greatly lowered by freezing. The reactivity of the formyl group changed depending on the redox state of the heme iron and the species of ligand.", "contents": "Change in effective pH of salt solutions on freezing, as evidenced by altered reactivities of heme alpha towards carbonyl reagents. Addition of NaHSO3 or HCN to the formyl group of heme alpha was greatly accelerated by freezing reaction mixtures prepared in aq. Na2CO3, and freezing resulted in characteristic color and spectral changes of the solutions. Similar changes were observed on decreasing the pH of alkaline reaction mixtures with HCl at room temperature, indicating that the effective pH of certain salt solutions is greatly lowered by freezing. The reactivity of the formyl group changed depending on the redox state of the heme iron and the species of ligand."}
{"id": "PMID:239934", "title": "Proteolytic degradation of hemoglobin-haptoglobin complex by lysosomal enzymes from rat liver.", "content": "The catabolic degradation of hemoglobin and of its complex with haptoglobin by lysosomal enzymes from rat liver was studied with special emphasis on the action of cathepsins D and E. The digestion of free hemoglobin can be mainly attributed to the action of cathepsin D [EC 3.4.23.5], while the digestion of the complex in the pH rand 2-3 is due more to the action of cathepsin E than that of cathepsin D. The enzymic activities of both cathepsins were strongly inhibited by pepstatin, and 4M urea inactivated cathepsin E. Measurements of the peroxidase activity and optical rotatory dispersion of the hemoglobin-haptoglobin complex showed that the complex suffered rapid denaturation below pH 2.9.", "contents": "Proteolytic degradation of hemoglobin-haptoglobin complex by lysosomal enzymes from rat liver. The catabolic degradation of hemoglobin and of its complex with haptoglobin by lysosomal enzymes from rat liver was studied with special emphasis on the action of cathepsins D and E. The digestion of free hemoglobin can be mainly attributed to the action of cathepsin D [EC 3.4.23.5], while the digestion of the complex in the pH rand 2-3 is due more to the action of cathepsin E than that of cathepsin D. The enzymic activities of both cathepsins were strongly inhibited by pepstatin, and 4M urea inactivated cathepsin E. Measurements of the peroxidase activity and optical rotatory dispersion of the hemoglobin-haptoglobin complex showed that the complex suffered rapid denaturation below pH 2.9."}
{"id": "PMID:239935", "title": "Photooxidation of histidine and tryptophan residues of papain in the presence of methylene blue.", "content": "Papain [EC 3.4.22.2] was photooxidized using methylene blue as a sensitizer. The photooxidzed enzyme lost its caseinolytic activity and had significantly decreased histidine and tryptophan contents. The tyrosine content was the same before and after the photooxidation. The SH content of the photooxidized enzyme, as determined after reduction with dithiothreitol, was also unchanged. The loss of histidine was always slower than the loss of enzymatic activity, being less than one residue per molecule even when the enzymatic activity was completely lost. However, the inactivation and the oxidation of a histidine residue were pH-dependent in a similar fashion in the pH range of 5.0-8.0, the pH profiles conforming to theoretical titration curves with apparent pKa values of 6.6 and 6.7, respectively. The fact that the ionization of a histidine residue in papain has a normal imidazole pKa value is entirely in accord with the finding for stem bromelain [EC 3.4.22.4] (Murachi, T., Tsudzuki, T., & Okumura, K. (1975) Biochemistry 14, 249-255), and is of great significance in relation to the mechanism of catalysis by these enzymes.", "contents": "Photooxidation of histidine and tryptophan residues of papain in the presence of methylene blue. Papain [EC 3.4.22.2] was photooxidized using methylene blue as a sensitizer. The photooxidzed enzyme lost its caseinolytic activity and had significantly decreased histidine and tryptophan contents. The tyrosine content was the same before and after the photooxidation. The SH content of the photooxidized enzyme, as determined after reduction with dithiothreitol, was also unchanged. The loss of histidine was always slower than the loss of enzymatic activity, being less than one residue per molecule even when the enzymatic activity was completely lost. However, the inactivation and the oxidation of a histidine residue were pH-dependent in a similar fashion in the pH range of 5.0-8.0, the pH profiles conforming to theoretical titration curves with apparent pKa values of 6.6 and 6.7, respectively. The fact that the ionization of a histidine residue in papain has a normal imidazole pKa value is entirely in accord with the finding for stem bromelain [EC 3.4.22.4] (Murachi, T., Tsudzuki, T., & Okumura, K. (1975) Biochemistry 14, 249-255), and is of great significance in relation to the mechanism of catalysis by these enzymes."}
{"id": "PMID:239936", "title": "The pH jump study of enzyme proteins. I. Liquefying alpha-amylase from Bacillus subtilis.", "content": "Rapid conformational changes due to pH jump were studied kinetically at 25 degrees mainly by the stopped-flow method using liquefying alpha-amylase from Bacillus subtilis [EC 3.2.1-.1, liquefying]. First, the conformational change due to a pH jump produced by mixing with alkali was monitored as a function of time at 245 nm through the ionization of phenolic hydroxyl groups of tyrosine residues which were originally buried and finally become exposed due to the pH jump. Three distinct phases of conformational change were clearly recognized by this method by varying the final pH values. Each phase involved the exposure of an essentially definite number of tyrosine residues, whose rate constant was crucially dependent on pH. Second, these phases of conformational change were subjected to examination in terms of the optical rotation change at 411 nm and the reversibility upon reverse pH jump with respect to conformational reconstitution, as observed through the protonation ofphenolic hydroxyl groups of ionized tyrosine residues and the enzyme activity. The first phase, which occurs above pH 12.5, involves no change in the optical rotation and is reversible as observed by the above two monitoring methods. In contrast, the other two phases, which are observed above pH 12.7, are accompanied by an optical rotation change and no appreciable reversibility was detected by these methods.", "contents": "The pH jump study of enzyme proteins. I. Liquefying alpha-amylase from Bacillus subtilis. Rapid conformational changes due to pH jump were studied kinetically at 25 degrees mainly by the stopped-flow method using liquefying alpha-amylase from Bacillus subtilis [EC 3.2.1-.1, liquefying]. First, the conformational change due to a pH jump produced by mixing with alkali was monitored as a function of time at 245 nm through the ionization of phenolic hydroxyl groups of tyrosine residues which were originally buried and finally become exposed due to the pH jump. Three distinct phases of conformational change were clearly recognized by this method by varying the final pH values. Each phase involved the exposure of an essentially definite number of tyrosine residues, whose rate constant was crucially dependent on pH. Second, these phases of conformational change were subjected to examination in terms of the optical rotation change at 411 nm and the reversibility upon reverse pH jump with respect to conformational reconstitution, as observed through the protonation ofphenolic hydroxyl groups of ionized tyrosine residues and the enzyme activity. The first phase, which occurs above pH 12.5, involves no change in the optical rotation and is reversible as observed by the above two monitoring methods. In contrast, the other two phases, which are observed above pH 12.7, are accompanied by an optical rotation change and no appreciable reversibility was detected by these methods."}
{"id": "PMID:239937", "title": "Myosin from molluscan abalone, Haliotis discus. Isolation and enzymatic properties.", "content": "Actomyosin was extracted from smooth muscle of molluscan abalone with 0.1 M PPit pH 6.4. Myosin was separated from the actomyosin by centrifugation at 100,000 X g in the presence of 5 mM ATP and 10 mM MgCl2. Myosin in the supernatant was further purified by gel filtration on a Sepharose 4B column. Paramyosin contamination of the actomyosin preparation interfered with the isolation of myosin and complete removal of actin and paramyosin from the myosin has not been accomplished. The myosin appeared to consist of a single f-chain and a single g-chain, as examined by SDS-disc electrophoresis in 8 or 13.7% acrylamide gel. The ATPase [EC 3.6.1.3] activity of this myosin in 0.5 M KCL at neutral pH and at 0 degrees was rather unstable and decreased by 10-20% per day. The effects of rho-chloromercuribenzoate and EDTA on the ATPase activity were similar to those observed with other smooth muscle myosin but the dependence upon pH or KCL concentration was different.", "contents": "Myosin from molluscan abalone, Haliotis discus. Isolation and enzymatic properties. Actomyosin was extracted from smooth muscle of molluscan abalone with 0.1 M PPit pH 6.4. Myosin was separated from the actomyosin by centrifugation at 100,000 X g in the presence of 5 mM ATP and 10 mM MgCl2. Myosin in the supernatant was further purified by gel filtration on a Sepharose 4B column. Paramyosin contamination of the actomyosin preparation interfered with the isolation of myosin and complete removal of actin and paramyosin from the myosin has not been accomplished. The myosin appeared to consist of a single f-chain and a single g-chain, as examined by SDS-disc electrophoresis in 8 or 13.7% acrylamide gel. The ATPase [EC 3.6.1.3] activity of this myosin in 0.5 M KCL at neutral pH and at 0 degrees was rather unstable and decreased by 10-20% per day. The effects of rho-chloromercuribenzoate and EDTA on the ATPase activity were similar to those observed with other smooth muscle myosin but the dependence upon pH or KCL concentration was different."}
{"id": "PMID:239938", "title": "Binding of substrate analogues to hen egg-white lysozyme with 2-nitrophenylsulfenylated tryptophan 62.", "content": "The pH dependence of the extrinsic circular dichroic (CD) band at 375 nm of hen egg-white lysozyme [EC 3.2.1.17] in which Trp 62 had selectively 2-nitrophenylsulfenylated (NPS-lysozyme) was studied. This pH dependence was interpreted in terms of the participation of Glu 35 (pK 6.2), Asp 101 (pK 4.6), and Asp 66 (pK1.5). The fact that the ionization of Glu 35 affects the extrinsic CD band of the NPS chromophore attached to Trp 62 confirms the presence of a relation between the state of Trp 62 and the ionization state of one of the catalytic groups, Glu 35, in hen lysozyme, as proposed by Ikeda and Hamaguchi (J. Biochem., 74, 221-230 (1973)). The pH dependence of the binding constants of the dimer and trimer of N-acetylglucosamine (GlcNAc) and the beta-methyl glycoside of GlcNAc (beta-methyl-GlcNAc) to NPS-lysozyme were studied by measuring the changes in the extrinsic CD band. The changes in the CD spectrum on the binding of (GlcNAc)3 and (GlcNAc)2 were very similar to each other but were different from that on the binding of beta-methyl-GlcNAc. However, beta-methyl-GlcNAc competitively inhibited the binding of (GlcNAc)2 to NPS-lysozyme. The binding constants of the three saccharides to NPS-lysozyme were much smaller than those for intact lysozyme. The pH dependence of the binding constants of (GlcNAc)2 and (GlcNAc)3 were interpreted in terms of the participation of Glu 35 (pK 6.2), Asp 52 (pK 3.3), Asp 101 (pK 4.6), and Asp 66 (pK 1.5). These pK values are very similar to those for intact lysozyme, as determined by Kuramitsu et al. (J. Biochem., 76, 671-683 (1974); 77, 291-301 (1975). Comparison of the binding constants of Mn2qnd Co2'ons to the catalytic carboxyls of NPS-lysozyme with those to intact lysozyme also indicated that the catalytic site of NPS-lysozyme is scarcely affected by this modification. When (GlcNAc)2 or (GlcNAc)3 is bound to NPS-lysozyme, pK shifts of Glu 35, Asp 101, and Asp 66 occurred in the same directions as for intact lysozyme. In addition, a pK shift of Asp 52, which has not been observed for intact lysozyme, occurred. The participation of Asp 52 was also observed in the binding of beta-methyl-GlcNAc. However, the binding of the monomer to NPS-lysozyme produced no significant pK shifts of Glu 35 and Asp 101, in contrast to the situation for intact lysozyme. These facts indicate a small difference in the binding orientation of the saccharides between the modified and intact lysozymes.", "contents": "Binding of substrate analogues to hen egg-white lysozyme with 2-nitrophenylsulfenylated tryptophan 62. The pH dependence of the extrinsic circular dichroic (CD) band at 375 nm of hen egg-white lysozyme [EC 3.2.1.17] in which Trp 62 had selectively 2-nitrophenylsulfenylated (NPS-lysozyme) was studied. This pH dependence was interpreted in terms of the participation of Glu 35 (pK 6.2), Asp 101 (pK 4.6), and Asp 66 (pK1.5). The fact that the ionization of Glu 35 affects the extrinsic CD band of the NPS chromophore attached to Trp 62 confirms the presence of a relation between the state of Trp 62 and the ionization state of one of the catalytic groups, Glu 35, in hen lysozyme, as proposed by Ikeda and Hamaguchi (J. Biochem., 74, 221-230 (1973)). The pH dependence of the binding constants of the dimer and trimer of N-acetylglucosamine (GlcNAc) and the beta-methyl glycoside of GlcNAc (beta-methyl-GlcNAc) to NPS-lysozyme were studied by measuring the changes in the extrinsic CD band. The changes in the CD spectrum on the binding of (GlcNAc)3 and (GlcNAc)2 were very similar to each other but were different from that on the binding of beta-methyl-GlcNAc. However, beta-methyl-GlcNAc competitively inhibited the binding of (GlcNAc)2 to NPS-lysozyme. The binding constants of the three saccharides to NPS-lysozyme were much smaller than those for intact lysozyme. The pH dependence of the binding constants of (GlcNAc)2 and (GlcNAc)3 were interpreted in terms of the participation of Glu 35 (pK 6.2), Asp 52 (pK 3.3), Asp 101 (pK 4.6), and Asp 66 (pK 1.5). These pK values are very similar to those for intact lysozyme, as determined by Kuramitsu et al. (J. Biochem., 76, 671-683 (1974); 77, 291-301 (1975). Comparison of the binding constants of Mn2qnd Co2'ons to the catalytic carboxyls of NPS-lysozyme with those to intact lysozyme also indicated that the catalytic site of NPS-lysozyme is scarcely affected by this modification. When (GlcNAc)2 or (GlcNAc)3 is bound to NPS-lysozyme, pK shifts of Glu 35, Asp 101, and Asp 66 occurred in the same directions as for intact lysozyme. In addition, a pK shift of Asp 52, which has not been observed for intact lysozyme, occurred. The participation of Asp 52 was also observed in the binding of beta-methyl-GlcNAc. However, the binding of the monomer to NPS-lysozyme produced no significant pK shifts of Glu 35 and Asp 101, in contrast to the situation for intact lysozyme. These facts indicate a small difference in the binding orientation of the saccharides between the modified and intact lysozymes."}
{"id": "PMID:239939", "title": "L-fucose metabolism in mammals. Kinetic studies on pork liver 2-keto-3-deoxy-L-fuconate:NAD+ oxidoreductase.", "content": "Pork liver 2-keto-3-deoxy-L-fuconate:NAD+ oxidoreductase has been shown to convert 2-keto-3-deoxy-L-fuconate to a 6-carbon acid tentatively identified as 2,4(or 5)-diketo-5(or 4)-monohydroxyhexanoate. The enzyme has a pH optimum of 10. 5 or higher. It is stabilized by dithiothereitol and inhibited by p-hydroxymercuribenzoate and heavy metals (Ag+, Hg2+, Co2+, Cd2+, Pb2+, Zn2+, and Cu2+), suggesting the presence of a functionally essential sulfhydryl group; pre-treatment of enzyme with NAD+ prevents inhibition by p-hydrocymercuribenzoate and heavy metals indicating that this sulfhydryl group may be near the NAD+ binding site. The enzyme has an absolute requirement for NAD+; NADP+ is an ineffective coenzyme. Several lines of evidence indicate that the same enzyme acts on both 2-keto-3-deocy-L-fuconate and 2-keto-3-deoxy-D-arabonate; thus, the pure enzyme acts on both substrates, the two substrates have very similar kinetic parameters (Km values are: 2-keto-3-deocy-L-fuconate, 0.20 mM; 2-keto-3-deoxy-D-arabonate, 0.25 mM; NAD+ for either substrate, 0.22 to 0.25 mM), the two substrates show identical pH and temperature profiles and the two substrates compete for common enzyme active sites. A large number of other sugars and sugar acids, including several 2-keto-3-deoxyaldonates, were ineffective as substrates. The dehydrogenase was also found in calf, beef, lamb, mouse, and rat liver. These studies when considered together with previous studies on the metabolism of L-fucose in pork liver indicate the presence of a soluble enzyme pathway capable of converting L-fucose to 2,4(or 5)-diketo-5(or 4)-monohydroxyhexanoate; this pathway can also convert D-arabinose, and probably L-galactose, to the analogous derivatives (diketomonohydroxypentanoate and diketodihydroxyhexanoate, respectively.", "contents": "L-fucose metabolism in mammals. Kinetic studies on pork liver 2-keto-3-deoxy-L-fuconate:NAD+ oxidoreductase. Pork liver 2-keto-3-deoxy-L-fuconate:NAD+ oxidoreductase has been shown to convert 2-keto-3-deoxy-L-fuconate to a 6-carbon acid tentatively identified as 2,4(or 5)-diketo-5(or 4)-monohydroxyhexanoate. The enzyme has a pH optimum of 10. 5 or higher. It is stabilized by dithiothereitol and inhibited by p-hydroxymercuribenzoate and heavy metals (Ag+, Hg2+, Co2+, Cd2+, Pb2+, Zn2+, and Cu2+), suggesting the presence of a functionally essential sulfhydryl group; pre-treatment of enzyme with NAD+ prevents inhibition by p-hydrocymercuribenzoate and heavy metals indicating that this sulfhydryl group may be near the NAD+ binding site. The enzyme has an absolute requirement for NAD+; NADP+ is an ineffective coenzyme. Several lines of evidence indicate that the same enzyme acts on both 2-keto-3-deocy-L-fuconate and 2-keto-3-deoxy-D-arabonate; thus, the pure enzyme acts on both substrates, the two substrates have very similar kinetic parameters (Km values are: 2-keto-3-deocy-L-fuconate, 0.20 mM; 2-keto-3-deoxy-D-arabonate, 0.25 mM; NAD+ for either substrate, 0.22 to 0.25 mM), the two substrates show identical pH and temperature profiles and the two substrates compete for common enzyme active sites. A large number of other sugars and sugar acids, including several 2-keto-3-deoxyaldonates, were ineffective as substrates. The dehydrogenase was also found in calf, beef, lamb, mouse, and rat liver. These studies when considered together with previous studies on the metabolism of L-fucose in pork liver indicate the presence of a soluble enzyme pathway capable of converting L-fucose to 2,4(or 5)-diketo-5(or 4)-monohydroxyhexanoate; this pathway can also convert D-arabinose, and probably L-galactose, to the analogous derivatives (diketomonohydroxypentanoate and diketodihydroxyhexanoate, respectively."}
{"id": "PMID:239940", "title": "pH dependence of the cooperative interactions and conformation of tryptophan oxygenase.", "content": "Allosteric interactions in the cupro-heme enzyme tryptophan oxygenase (EC 1.13.11.11) of Pseudomonas acidovorans are shown to be pH-dependent. Increasing the assay pH from 6.0 to 8.0 progressively desensitizes the enzyme from both homotropic and heterotropic ligand interactions. This pH-dependent reversible transition has a pK of 6.2. Hill coefficients for the substrate L-tryptophan of 2.0 and 1.4 were measured at pH 6.0 and pH 7.0, respectively. In attempting to identify the enzymatic residue (or residues) responsible for these pH-dependent effects, the enzyme was observed to be irreversibly inactivated by photoinduced oxidation in the presence of the sensitizer, methylene blue. The photoinactivated enzyme showed a loss of one-half its Soret (405 nm) absorption which accompanied the loss of one-half its heme and histidine contents. This first order photoinduced inactivation was pH-dependent and corresponded to a requirement for a protonated species with a pK of 6.2. These results suggest that histidine residues may be involved in the catalytic function and in mediating cooperative interactions of tryptophan oxygenase. Absolute and difference sedimentation velocity analyses indicate that the molecule undergoes a conformational transition when the pH is decreased from pH 8.0 to pH 6.0. This conformational alteration, measured as a 3.9% increase in S20, w can be regarded as an equivalent decrease in the frictional coefficient. If, a more or less spherical shape to the molecule is assumed, then, the 3.9% decrease in the frictional coefficient between pH 8.0 and 6.0 corresponds to a 12% decrease in apparent hydrodynamic volume of the enzyme. Thus, protonation of an enzymatic moiety, possibly histidine, determines both the conformational and functional interactions between enzymatic sites.", "contents": "pH dependence of the cooperative interactions and conformation of tryptophan oxygenase. Allosteric interactions in the cupro-heme enzyme tryptophan oxygenase (EC 1.13.11.11) of Pseudomonas acidovorans are shown to be pH-dependent. Increasing the assay pH from 6.0 to 8.0 progressively desensitizes the enzyme from both homotropic and heterotropic ligand interactions. This pH-dependent reversible transition has a pK of 6.2. Hill coefficients for the substrate L-tryptophan of 2.0 and 1.4 were measured at pH 6.0 and pH 7.0, respectively. In attempting to identify the enzymatic residue (or residues) responsible for these pH-dependent effects, the enzyme was observed to be irreversibly inactivated by photoinduced oxidation in the presence of the sensitizer, methylene blue. The photoinactivated enzyme showed a loss of one-half its Soret (405 nm) absorption which accompanied the loss of one-half its heme and histidine contents. This first order photoinduced inactivation was pH-dependent and corresponded to a requirement for a protonated species with a pK of 6.2. These results suggest that histidine residues may be involved in the catalytic function and in mediating cooperative interactions of tryptophan oxygenase. Absolute and difference sedimentation velocity analyses indicate that the molecule undergoes a conformational transition when the pH is decreased from pH 8.0 to pH 6.0. This conformational alteration, measured as a 3.9% increase in S20, w can be regarded as an equivalent decrease in the frictional coefficient. If, a more or less spherical shape to the molecule is assumed, then, the 3.9% decrease in the frictional coefficient between pH 8.0 and 6.0 corresponds to a 12% decrease in apparent hydrodynamic volume of the enzyme. Thus, protonation of an enzymatic moiety, possibly histidine, determines both the conformational and functional interactions between enzymatic sites."}
{"id": "PMID:239941", "title": "Guanylate cyclase in Escherichia coli. Purification and properties.", "content": "Guanylate cyclase has been purified from extracts of Escherichia coli. After a 1000-fold purification, the enzyme contains only minor contaminants as judged by disc gel electrophoresis. The Km for GTP is approximately 7 times 10(-5) M and the optimal pH is 8.0. More activity is observed with Mn2+ than with Mg2+, and maximal activity is observed at 0.14 mM Mn2+ and 1.4 mM Mg2+. Based on its behavior on Sephadex G-100, the molecular weight of E. coli guanylate cyclase is about 30,000. Disc gel electrophoretic analysis indicates that the enzyme consists of a single polypeptide chain. Guanylate cyclase does not form 3':5'-AMP from ATP, and therefore, is distinct from adenylate cyclase.", "contents": "Guanylate cyclase in Escherichia coli. Purification and properties. Guanylate cyclase has been purified from extracts of Escherichia coli. After a 1000-fold purification, the enzyme contains only minor contaminants as judged by disc gel electrophoresis. The Km for GTP is approximately 7 times 10(-5) M and the optimal pH is 8.0. More activity is observed with Mn2+ than with Mg2+, and maximal activity is observed at 0.14 mM Mn2+ and 1.4 mM Mg2+. Based on its behavior on Sephadex G-100, the molecular weight of E. coli guanylate cyclase is about 30,000. Disc gel electrophoretic analysis indicates that the enzyme consists of a single polypeptide chain. Guanylate cyclase does not form 3':5'-AMP from ATP, and therefore, is distinct from adenylate cyclase."}
{"id": "PMID:239942", "title": "Cascade control of Escherichia coli glutamine synthetase. Properties of the PII regulatory protein and the uridylyltransferase-uridylyl-removing enzyme.", "content": "The PII regulatory protein of Escherichia coli glutamine synthetase exists in two interconvertible forms: a uridylylated form (PIID) which promotes the deadenylylation of glutamine synthetase and an unmodified form (PIIA) which promotes the adenylylation of glutamine synthetase (Mangum, J.H., Magni, G., and Stadtman, E.R. (1973) Arch. Biochem. Biophys. 158, 514-525). PII has been purified to homogeneity. Its molecular weight is 44,000. The protein is composed of four subunits, each with a molecular weight of approximately 11,000. The subunits are identical as judged by: (a) the homogeneity of the subunits in sodium dodecyl sulfate, 8 M urea, and 6 M guanidine HCl; (b) the minimal molecular weight calculated from the amino acid composition; and (c) the isolation of only two tryptic peptides containing tyrosine (there are 8 tyrosyl residues per 44,000 molecular species). Following iodination of PIIA and PIID with 125I in the presence of chloramine-T, tryptic digestion yields two radioactive peptides from PIIA and only one from PIID. Since a tyrosine with a substituted hydroxyl group cannot be iodinated, this result indicates that 1 tyrosyl residue in each subunit is modified by the covalent attachment of UMP. This conclusion is supported also by the fact that treatment of PIID with snake venom phosphodiesterase results in the release of covalently bound UMP and the stoichiometric appearance of phenolate ion (pH 13) as measured by ultraviolet absorption spectroscopy. The enzyme activities (uridylyl-removing) responsible for removal and (uridylytransferase) responsible for attachment of UMP to PII have been partially purified. These activities co-purify through a variety of procedures, including hydrophobic chromatography, and are stabilized by high ionic strength buffers. Whereas Mn2+ alone supports only uridylyl-removing activity, ATP, alpha-ketoglutarate, and Mg2+ support both uridylyl-removing and uridylyltransferase activities.", "contents": "Cascade control of Escherichia coli glutamine synthetase. Properties of the PII regulatory protein and the uridylyltransferase-uridylyl-removing enzyme. The PII regulatory protein of Escherichia coli glutamine synthetase exists in two interconvertible forms: a uridylylated form (PIID) which promotes the deadenylylation of glutamine synthetase and an unmodified form (PIIA) which promotes the adenylylation of glutamine synthetase (Mangum, J.H., Magni, G., and Stadtman, E.R. (1973) Arch. Biochem. Biophys. 158, 514-525). PII has been purified to homogeneity. Its molecular weight is 44,000. The protein is composed of four subunits, each with a molecular weight of approximately 11,000. The subunits are identical as judged by: (a) the homogeneity of the subunits in sodium dodecyl sulfate, 8 M urea, and 6 M guanidine HCl; (b) the minimal molecular weight calculated from the amino acid composition; and (c) the isolation of only two tryptic peptides containing tyrosine (there are 8 tyrosyl residues per 44,000 molecular species). Following iodination of PIIA and PIID with 125I in the presence of chloramine-T, tryptic digestion yields two radioactive peptides from PIIA and only one from PIID. Since a tyrosine with a substituted hydroxyl group cannot be iodinated, this result indicates that 1 tyrosyl residue in each subunit is modified by the covalent attachment of UMP. This conclusion is supported also by the fact that treatment of PIID with snake venom phosphodiesterase results in the release of covalently bound UMP and the stoichiometric appearance of phenolate ion (pH 13) as measured by ultraviolet absorption spectroscopy. The enzyme activities (uridylyl-removing) responsible for removal and (uridylytransferase) responsible for attachment of UMP to PII have been partially purified. These activities co-purify through a variety of procedures, including hydrophobic chromatography, and are stabilized by high ionic strength buffers. Whereas Mn2+ alone supports only uridylyl-removing activity, ATP, alpha-ketoglutarate, and Mg2+ support both uridylyl-removing and uridylyltransferase activities."}
{"id": "PMID:239943", "title": "Hemoglobin Abruzzo (beta143 (H21) His replaced by Arg). Consequences of altering the 2,3-diphosphoglycerate binding site.", "content": "Hemoglobin Abruzzo is an abnormal human hemoglobin with a substitution at a residue known to be involved in the binding of 2,3-diphosphoglyceric acid. It has increased oxygen affinity and reduced heme-heme interaction in the absence of organic or inorganic phosphate cofactors. In inorganic phosphate buffers the Bohr effect and heme-heme interaction are normal, but the oxygen affinity remains higher than that of hemoglobin A. CO combination in inorganic phosphate is more strongly autocatalytic than in normal hemoglobin and a slower rate of oxygen dissociation is observed. Although many of the functional differences of this variant may be attributed to the high oxygen affinity of the mutant beta chains, the interactions between subunits are also affected by the histidine to arginine substitution at beta143. Stripped hemoglobin Abruzzo appears to be significantly more dissociated than hemoglobin A. Kinetic studies indicate that interaction with organic or inorganic phosphates decreases its subunit dissociation. In all of the functional properties examined, hemoglobin Abruzzo is more sensitive to the allosteric influence of organic and inorganic anions than is hemoglobin A.", "contents": "Hemoglobin Abruzzo (beta143 (H21) His replaced by Arg). Consequences of altering the 2,3-diphosphoglycerate binding site. Hemoglobin Abruzzo is an abnormal human hemoglobin with a substitution at a residue known to be involved in the binding of 2,3-diphosphoglyceric acid. It has increased oxygen affinity and reduced heme-heme interaction in the absence of organic or inorganic phosphate cofactors. In inorganic phosphate buffers the Bohr effect and heme-heme interaction are normal, but the oxygen affinity remains higher than that of hemoglobin A. CO combination in inorganic phosphate is more strongly autocatalytic than in normal hemoglobin and a slower rate of oxygen dissociation is observed. Although many of the functional differences of this variant may be attributed to the high oxygen affinity of the mutant beta chains, the interactions between subunits are also affected by the histidine to arginine substitution at beta143. Stripped hemoglobin Abruzzo appears to be significantly more dissociated than hemoglobin A. Kinetic studies indicate that interaction with organic or inorganic phosphates decreases its subunit dissociation. In all of the functional properties examined, hemoglobin Abruzzo is more sensitive to the allosteric influence of organic and inorganic anions than is hemoglobin A."}
{"id": "PMID:239944", "title": "Transient state kinetic studies of proton liberation by myosin and subfragment 1.", "content": "Myosin and subfragment 1 give a maximum burst size of 0.25 to 0.30 protons per active site at pH 8 with ATP, alpha,beta-methylene-ATP, ADP, and adenylyl imidodiphosphate as substrates. The proton is derived from a change in conformation of the enzyme-substrate complex since it is produced by substrates which are not hydrolyzed. The rate constants for the binding of ATP and the proton release step in 0.1 M, 0.5 M, and 1.0 M KCl have been determined by analysis of the concentration dependence of the apparent rate. (see article)", "contents": "Transient state kinetic studies of proton liberation by myosin and subfragment 1. Myosin and subfragment 1 give a maximum burst size of 0.25 to 0.30 protons per active site at pH 8 with ATP, alpha,beta-methylene-ATP, ADP, and adenylyl imidodiphosphate as substrates. The proton is derived from a change in conformation of the enzyme-substrate complex since it is produced by substrates which are not hydrolyzed. The rate constants for the binding of ATP and the proton release step in 0.1 M, 0.5 M, and 1.0 M KCl have been determined by analysis of the concentration dependence of the apparent rate. (see article)"}
{"id": "PMID:239945", "title": "Alpha-methylisocitrate. A selective inhibitor of TPN-linked isocitrate dehydrogenase from bovine heart and rat liver.", "content": "Alpha-Methylisocitrate (3-hydroxy-1,2,3-butanetricarboxylate) is a potent inhibitor, competitive with isocitrate (1-hydroxy-1,2,3-propanetricarboxylate), of the TPN-linked isocitrate dehydrogenase from bovine heart and rat liver; it does not inhibit the DPN-specific enzyme from these tissues. In the presence of magnesium ion, values of Kis for DL-alpha-methylisocitrate for purified bovine heart enzyme, rat liver cytosol, and rat liver mitochondrial extract were in the range of 0.1 muM to 0.3 muM. This compared to values of apparent Km for DL-isocitrate for the same tissue preparations of 14 muM to 20 muM. One of the DL isomer pairs of alpha-methylisocitrate was inactive; the observations suggest that it is threo-alpha-methylisocitrate which inhibits TPN-linked isocitrate dehydrogenase. A method of synthesis of DL-threo-alpha-methylisocitric lactone (2-methyl-5-oxo-2,3-furandicarboxylic acid) from dimethyl trans-epoxymethylsuccinate and dimethylmalonate is described.", "contents": "Alpha-methylisocitrate. A selective inhibitor of TPN-linked isocitrate dehydrogenase from bovine heart and rat liver. Alpha-Methylisocitrate (3-hydroxy-1,2,3-butanetricarboxylate) is a potent inhibitor, competitive with isocitrate (1-hydroxy-1,2,3-propanetricarboxylate), of the TPN-linked isocitrate dehydrogenase from bovine heart and rat liver; it does not inhibit the DPN-specific enzyme from these tissues. In the presence of magnesium ion, values of Kis for DL-alpha-methylisocitrate for purified bovine heart enzyme, rat liver cytosol, and rat liver mitochondrial extract were in the range of 0.1 muM to 0.3 muM. This compared to values of apparent Km for DL-isocitrate for the same tissue preparations of 14 muM to 20 muM. One of the DL isomer pairs of alpha-methylisocitrate was inactive; the observations suggest that it is threo-alpha-methylisocitrate which inhibits TPN-linked isocitrate dehydrogenase. A method of synthesis of DL-threo-alpha-methylisocitric lactone (2-methyl-5-oxo-2,3-furandicarboxylic acid) from dimethyl trans-epoxymethylsuccinate and dimethylmalonate is described."}
{"id": "PMID:239946", "title": "Nicotinamide adenine dinucleotide phosphate-specific glutamate dehydrogenase of Neurospora. III. Inactivation by nitration of a tyrosine residue involved in coenzyme binding.", "content": "Neurospora glutamate dehydrogenase (NADP-specific) is rapidly inactivated upon reaction with tetranitromethane. This inactivation is completely prevented by the presence of coenzyme (NADP) or nicotinamide mononucleotide (NMN) but not by substrate. NADH, or 2'-monophosphoadenosine-5'-diphosphoribose. Amino acid analysis indicates that the primary effect of modification is nitration of a single residue of tyrosine per polypeptide chain. We have identified the reactive tyrosine by isolation of a single, uniquely labeled peptide after hydrolysis with trypsin followed by cleavage with cyanogen bromide. The modified residue proved to be tyrosine-168 in the linear sequence. This residue is not present in the part of the sequence that had been previously implicated as involved in the binding of the adenylate portion of the coenzyme. Both NMN and 2-monophosphoadenosine-5'-diphosphoribose act as competitive inhibitors of NADP in the oxidation of glutamate with Ki values of 4.65 x 10(-4) M and 4.30 x 10(-4) M, respectively. Thus, the specific protection afforded by NADP and NMN, but not by 2'-monophosphoadenosine-5'-diphosphoribose, indicates that tyrosine-168 is involved in binding the nicotinamide portion of the coenzyme.", "contents": "Nicotinamide adenine dinucleotide phosphate-specific glutamate dehydrogenase of Neurospora. III. Inactivation by nitration of a tyrosine residue involved in coenzyme binding. Neurospora glutamate dehydrogenase (NADP-specific) is rapidly inactivated upon reaction with tetranitromethane. This inactivation is completely prevented by the presence of coenzyme (NADP) or nicotinamide mononucleotide (NMN) but not by substrate. NADH, or 2'-monophosphoadenosine-5'-diphosphoribose. Amino acid analysis indicates that the primary effect of modification is nitration of a single residue of tyrosine per polypeptide chain. We have identified the reactive tyrosine by isolation of a single, uniquely labeled peptide after hydrolysis with trypsin followed by cleavage with cyanogen bromide. The modified residue proved to be tyrosine-168 in the linear sequence. This residue is not present in the part of the sequence that had been previously implicated as involved in the binding of the adenylate portion of the coenzyme. Both NMN and 2-monophosphoadenosine-5'-diphosphoribose act as competitive inhibitors of NADP in the oxidation of glutamate with Ki values of 4.65 x 10(-4) M and 4.30 x 10(-4) M, respectively. Thus, the specific protection afforded by NADP and NMN, but not by 2'-monophosphoadenosine-5'-diphosphoribose, indicates that tyrosine-168 is involved in binding the nicotinamide portion of the coenzyme."}
{"id": "PMID:239947", "title": "Molecular aspects of the inactivation of tryptophanyl transfer ribonucleic acid synthetase by N-ethylmaleimide.", "content": "The tryptic maps of tryptophanyl-tRNA synthetase from beef pancreas show that the 8 cysteinyl residues of the enzyme subunit are located, 2 by 2, on four different peptides. The kinetics of the incorporation of radioactivity from N-[ethyl-14C]ethylmaleimide into these peptides are compared in this paper with the kinetics of the changes of the catalytic properties of the enzyme occurring during alkylation. This comparison allows the identification of (a) the peptide carrying the cysteinyl residues located on the surface of the molecule, (b) the peptide carrying the deeply buried residues unmasked by the dissociation of the subunits, and (c) the peptide carrying the --SH group located in the vicinity of the binding site of tryptophan. The fourth peptide is shown to have a great sensitivity to pH with respect to the reactivity of its cysteinyl residues toward N-ethylmaleimide. The same unusual pH dependence is found for the rate of quenching of the intrinsic fluorescence of the protein during the alkylation, suggesting a strong sensitivity of the conformation of tryptophanyl-tRNA synthetase to pH in the range of 7 to 9.", "contents": "Molecular aspects of the inactivation of tryptophanyl transfer ribonucleic acid synthetase by N-ethylmaleimide. The tryptic maps of tryptophanyl-tRNA synthetase from beef pancreas show that the 8 cysteinyl residues of the enzyme subunit are located, 2 by 2, on four different peptides. The kinetics of the incorporation of radioactivity from N-[ethyl-14C]ethylmaleimide into these peptides are compared in this paper with the kinetics of the changes of the catalytic properties of the enzyme occurring during alkylation. This comparison allows the identification of (a) the peptide carrying the cysteinyl residues located on the surface of the molecule, (b) the peptide carrying the deeply buried residues unmasked by the dissociation of the subunits, and (c) the peptide carrying the --SH group located in the vicinity of the binding site of tryptophan. The fourth peptide is shown to have a great sensitivity to pH with respect to the reactivity of its cysteinyl residues toward N-ethylmaleimide. The same unusual pH dependence is found for the rate of quenching of the intrinsic fluorescence of the protein during the alkylation, suggesting a strong sensitivity of the conformation of tryptophanyl-tRNA synthetase to pH in the range of 7 to 9."}
{"id": "PMID:239948", "title": "5-Oxo-L-prolinase (L-pyroglutamate hydrolase). Purification and catalytic properties.", "content": "5-Oxo-L-prolinase, an enzyme that catalyzes the conversion of 5-oxo-L-proline (L-pyroglutamate; L-2-pyrrolidone-5-carboxylate) to L-glutamate coupled with the cleavage of ATP to ADP and Pi, has been purified about 1600-fold from rat kidney. Purification was carried out in the presence of 5-oxo-L-proline which protects the enzyme under a variety of conditions. An estimate of the molecular weight (about 325,000) was made by gel filtration on Sephadex G-200. K+ (or NH4+) and Mg2+ were required for activity. GTP, ITP, CTP, and UTP were much less active than ATP; dATP was 43% as active as ATP. ADP inhibited and addition of pyruvate kinase and phosphoenolpyruvate activated the reaction. The enzyme, which is protected during storage by dithiothreitol, is inhibited by p-hydroxymercuribenzoate, N-ethylmaleimide, and iodoacetamide. The apparent Km values for 5-oxo-L-proline and ATP are, respectively, 0.05 and 0.17 mM. The pH profile indicates a broad range of activity from about pH 5.5 to pH 11.2 with apparent maxima at about pH 7 and pH 9.7. The formation of Pi and glutamate was equimolar over a wide pH range. When the enzyme was incubated with ATP, Mg2+, K+, and L-2-imidazolidone-4-carboxylate or L-dihydroorotate, cleavage of ATP to ADP and Pi occurred, but no cleavage of the imino acid substrates was observed; when the enzyme was incubated under these conditions with 2-piperidone-6-carboxylate, 4-oxy-5-oxoproline, and 3-oxy-5-oxoproline, the corresponding dicarboxylic amino acids were formed, but the molar ratio of Pi to amino acid formation was significantly greater than unity.", "contents": "5-Oxo-L-prolinase (L-pyroglutamate hydrolase). Purification and catalytic properties. 5-Oxo-L-prolinase, an enzyme that catalyzes the conversion of 5-oxo-L-proline (L-pyroglutamate; L-2-pyrrolidone-5-carboxylate) to L-glutamate coupled with the cleavage of ATP to ADP and Pi, has been purified about 1600-fold from rat kidney. Purification was carried out in the presence of 5-oxo-L-proline which protects the enzyme under a variety of conditions. An estimate of the molecular weight (about 325,000) was made by gel filtration on Sephadex G-200. K+ (or NH4+) and Mg2+ were required for activity. GTP, ITP, CTP, and UTP were much less active than ATP; dATP was 43% as active as ATP. ADP inhibited and addition of pyruvate kinase and phosphoenolpyruvate activated the reaction. The enzyme, which is protected during storage by dithiothreitol, is inhibited by p-hydroxymercuribenzoate, N-ethylmaleimide, and iodoacetamide. The apparent Km values for 5-oxo-L-proline and ATP are, respectively, 0.05 and 0.17 mM. The pH profile indicates a broad range of activity from about pH 5.5 to pH 11.2 with apparent maxima at about pH 7 and pH 9.7. The formation of Pi and glutamate was equimolar over a wide pH range. When the enzyme was incubated with ATP, Mg2+, K+, and L-2-imidazolidone-4-carboxylate or L-dihydroorotate, cleavage of ATP to ADP and Pi occurred, but no cleavage of the imino acid substrates was observed; when the enzyme was incubated under these conditions with 2-piperidone-6-carboxylate, 4-oxy-5-oxoproline, and 3-oxy-5-oxoproline, the corresponding dicarboxylic amino acids were formed, but the molar ratio of Pi to amino acid formation was significantly greater than unity."}
{"id": "PMID:239949", "title": "Isolation and characterization of jack bean beta-galactosidase.", "content": "A simple procedure has been devised to isolate beta-galactosidase from jack bean meal. The final preparation gives one major protein banc in disc gel electrophoresis. The substrate specificity of this enzyme toward some natural oligosaccharides, glycoproteins, and sphingoglycolipids has been examined in detail. Among three isomers of N-acetyllactosamine, Galbeta1leads to4GlcNAc; while Galbeta1leads to3GlcNAc was hydrolyzed very slowly. This property can be used to distinguish the galactose linkage in asialo-GM1 (Galbeta1leads to3GalNAcbeta1leads to4Galbeta1leads to4Glcleads toCer) and that in lacto-N-neotetraosylceramide (Galbeta1leads to4GlcNAcbeta1leads to 3Galbeta1leads to4Glcleads toCer). For hydrolyzing glycolipids, the effect of sodium taurodeoxycholate and sodium taurochenodeoxycholate on the rate of hydrolysis was carefully examined. This enzyme hydrolyzes lactosylceramide and asialo-GM1 faster than GM1. These results suggest that in addition to the type and linkage of the penultimate sugar unit, the sugar unit at the distal position of the saccharide chain also affects the hydrolysis rate. It also readily liberates 80% D-galactosyl units from asialo alpha1-acid glycoprotein. Escherichia coli beta-galactosidase on the other hand cannot hydrolyze asialo-alpha1-acid glycoprotein, lactosylceramide, GM1, asialo-GM1, and lacto-N-neotetraosylceramide. The molecular weight of this enzyme is about 75,000 and the isoelectric point is pH 8.0. With p-nitrophenyl beta-D-galactopyranoside as substrate, optimal activity occurs at pH 2.8 with glycine-HCl buffer and at pH 3.5 with citrate-phosphate buffer. With lactose as substrate, the pH optimum in these two buffers are 2.8 and 4.0, respectively. Km values for p-nitrophenyl beta-D-galactopyranoside, o-nitrophenyl beta-D-galactopyranoside and lactose are 0.51 mM, 0.63 mM, and 12.23 mM, respectively. Many inhibitors for this enzyme including inorganic ions, monosaccharides, and glycosides are investigated. In contrast to E. coli beta-galactosidase, jack bean beta-galactosidase is not inhibited by p-aminophenyl thio-beta-D-galactopyranoside.", "contents": "Isolation and characterization of jack bean beta-galactosidase. A simple procedure has been devised to isolate beta-galactosidase from jack bean meal. The final preparation gives one major protein banc in disc gel electrophoresis. The substrate specificity of this enzyme toward some natural oligosaccharides, glycoproteins, and sphingoglycolipids has been examined in detail. Among three isomers of N-acetyllactosamine, Galbeta1leads to4GlcNAc; while Galbeta1leads to3GlcNAc was hydrolyzed very slowly. This property can be used to distinguish the galactose linkage in asialo-GM1 (Galbeta1leads to3GalNAcbeta1leads to4Galbeta1leads to4Glcleads toCer) and that in lacto-N-neotetraosylceramide (Galbeta1leads to4GlcNAcbeta1leads to 3Galbeta1leads to4Glcleads toCer). For hydrolyzing glycolipids, the effect of sodium taurodeoxycholate and sodium taurochenodeoxycholate on the rate of hydrolysis was carefully examined. This enzyme hydrolyzes lactosylceramide and asialo-GM1 faster than GM1. These results suggest that in addition to the type and linkage of the penultimate sugar unit, the sugar unit at the distal position of the saccharide chain also affects the hydrolysis rate. It also readily liberates 80% D-galactosyl units from asialo alpha1-acid glycoprotein. Escherichia coli beta-galactosidase on the other hand cannot hydrolyze asialo-alpha1-acid glycoprotein, lactosylceramide, GM1, asialo-GM1, and lacto-N-neotetraosylceramide. The molecular weight of this enzyme is about 75,000 and the isoelectric point is pH 8.0. With p-nitrophenyl beta-D-galactopyranoside as substrate, optimal activity occurs at pH 2.8 with glycine-HCl buffer and at pH 3.5 with citrate-phosphate buffer. With lactose as substrate, the pH optimum in these two buffers are 2.8 and 4.0, respectively. Km values for p-nitrophenyl beta-D-galactopyranoside, o-nitrophenyl beta-D-galactopyranoside and lactose are 0.51 mM, 0.63 mM, and 12.23 mM, respectively. Many inhibitors for this enzyme including inorganic ions, monosaccharides, and glycosides are investigated. In contrast to E. coli beta-galactosidase, jack bean beta-galactosidase is not inhibited by p-aminophenyl thio-beta-D-galactopyranoside."}
{"id": "PMID:239950", "title": "Liver cytosol corticosteroid binder IB, a new binding protein.", "content": "A new binding protein named corticosteroid Binder IB elutes just after ligandin in DEAE-Sephadex chromatograms. It has been partially purified to about 2500-fold over cytosol proteins. Calculation of the number of steroid binding sites, assuming one site per molecule of Binder IB fraction after DEAE-Sephadex chromatography, suggests a concentration of the binding protein of about 0.0004% of cytosol proteins. Its pI value is judged to be 7.5 to 8 from it elution position on DEAE-Sephadex chromatograms. IB has an apparent molecular weight of 30,500 +/- 10% by gel filtration and a Stokes radius of 20 A. Binder IB binds radioactive dexamethasone, cortisol, and corticosterone in vitro with estimated KD values of 1, 13, and 25 nM, respectively. Saturation curves are abnormal, showing two phases. The saturation curves within the physiological range of concentrations of steroid are abnormal and suggestive of cooperativity. The second phase, at concentrations of glucocortidoids above saturation and physiological levels, shows extensive binding. After fractionation from other steroid binding proteins, the specificity of binding from competition studies in vitro is dexamethasone greater than or equal to cortisol = corticosterone = estradiol-17beta greater than or equal to deoxycorticosterone = dihydrotestosterone greater than aldosterone = cortexolone greater than testosterone. Other steroids tested are less efficient ligands. The binding is probably noncovalent, but strong; and the complex becomes more dissociable as purification proceeds, suggesting a conformational change in the protein. Storage and rebinding with steroid are possible throughout the purification process, although extensive ligand dissociation and denaturation of the protein occur after the final purification step. Binding in vitro is temperature-sensitive and binding is sharply pH dependent with an optimum at 7.5. The ligand is the unmetabolized steroid as judged by extraction of steroid-IB complex with methylene chloride  and subsequent thin layer chromatography. The physiological function of this protein is unknown at present and purification fo the major corticosteroid hormone receptor to homogeneity may be required before the function of Binder IB is fully understood.", "contents": "Liver cytosol corticosteroid binder IB, a new binding protein. A new binding protein named corticosteroid Binder IB elutes just after ligandin in DEAE-Sephadex chromatograms. It has been partially purified to about 2500-fold over cytosol proteins. Calculation of the number of steroid binding sites, assuming one site per molecule of Binder IB fraction after DEAE-Sephadex chromatography, suggests a concentration of the binding protein of about 0.0004% of cytosol proteins. Its pI value is judged to be 7.5 to 8 from it elution position on DEAE-Sephadex chromatograms. IB has an apparent molecular weight of 30,500 +/- 10% by gel filtration and a Stokes radius of 20 A. Binder IB binds radioactive dexamethasone, cortisol, and corticosterone in vitro with estimated KD values of 1, 13, and 25 nM, respectively. Saturation curves are abnormal, showing two phases. The saturation curves within the physiological range of concentrations of steroid are abnormal and suggestive of cooperativity. The second phase, at concentrations of glucocortidoids above saturation and physiological levels, shows extensive binding. After fractionation from other steroid binding proteins, the specificity of binding from competition studies in vitro is dexamethasone greater than or equal to cortisol = corticosterone = estradiol-17beta greater than or equal to deoxycorticosterone = dihydrotestosterone greater than aldosterone = cortexolone greater than testosterone. Other steroids tested are less efficient ligands. The binding is probably noncovalent, but strong; and the complex becomes more dissociable as purification proceeds, suggesting a conformational change in the protein. Storage and rebinding with steroid are possible throughout the purification process, although extensive ligand dissociation and denaturation of the protein occur after the final purification step. Binding in vitro is temperature-sensitive and binding is sharply pH dependent with an optimum at 7.5. The ligand is the unmetabolized steroid as judged by extraction of steroid-IB complex with methylene chloride  and subsequent thin layer chromatography. The physiological function of this protein is unknown at present and purification fo the major corticosteroid hormone receptor to homogeneity may be required before the function of Binder IB is fully understood."}
{"id": "PMID:239951", "title": "Pyridoxal 5'-phosphate, a fluorescent probe in the active site of aspartate transcarbamylase.", "content": "Pyridoxal-P reacts specifically with a single lysine residue at the active site of Escherichia coli aspartate transcarbamylase (Greenwell, P., Jewett, S. L., and Stark, G. R. (1973) J. Biol. Chem. 248, 5994-6001). Reduction of the Schiff base with sodium borohydride, succinylation of the remaining lysine residues, and digestion with trypsin result in formation of a single pyridoxyl peptide, which was purified to homogeneity after chromatography on DEAE-cellulose, treatment with alkaline phosphatase, and rechromatography. Amino acid composition and the results of limited sequential degradation showed that this peptide corresponds to residues 62 to 98 in the sequence of Konigsberg and co-workers, and contains 2 residues of lysine (Henderson, L., Roy, D., Martin, D., and Konigsberg, W., personal communication). By similar isolation, a second peptide was obtained from unsuccinylated catalytic subunit, containing only the pyridoxylated lysine, which corresponds to Lys-80. Derivatives of catalytic subunit containing an average of either one, two, or three pyridoxamine-P moieties per trimer have been prepared by reduction. These species, which retain catalytic activity in proportion to their unmodified active sites, were recombined with regulatory subunit to prepare partially modified derivatives of native aspartate transcarbamylase. At pH 8, fluorescence emission bands were observed at 340 nm, due to aromatic amino acids in the protein, and at 395 nm, due to the pyridoxamine-P moiety. Upon excitation at 280 nm energy transfer from protein to pyridoxamine-P was approximately 15%. The properties of the probe were used to study changes accompanying the binding of substrates and inhibitors. The effects of CTP and ATP were small. With the transition state analog N-(phosphonacetyl)-L-aspartate (PALA) or the substrate carbamyl-P, two types of response were observed. Derivatives of catalytic subunit and native enzyme which contain some unmodified sites and hence retain partial catalytic activity gave large increases in fluorescence at 395 nm. However, fully modified inactive derivatives gave much smaller increases. A derivative of native enzyme containing one triply modified and one unmodified catalytic subunit behaved like the other partially modified species. These results indicate that there is communication among the active sites of different catalytic trimers in modified native enzyme, as well as among active sites within the same modified catalytic trimer. The increases in fluorescence result from a red shift of the absorption maximum of the pyridoxamine-P moiety from 315 to 325 nm, which increases the absorbance at the excitation wavelength for fluorescence. At pH 7, the absorption spectrum is already shifted and, consequently, the binding of PALA and carbamyl-P has little effect on the fluorescence. Therefore, the binding of these compounds at pH 8.0 must cause a structural change in the protein, which in turn causes protonation of a group in the modified active sites, altering the spectral properties.", "contents": "Pyridoxal 5'-phosphate, a fluorescent probe in the active site of aspartate transcarbamylase. Pyridoxal-P reacts specifically with a single lysine residue at the active site of Escherichia coli aspartate transcarbamylase (Greenwell, P., Jewett, S. L., and Stark, G. R. (1973) J. Biol. Chem. 248, 5994-6001). Reduction of the Schiff base with sodium borohydride, succinylation of the remaining lysine residues, and digestion with trypsin result in formation of a single pyridoxyl peptide, which was purified to homogeneity after chromatography on DEAE-cellulose, treatment with alkaline phosphatase, and rechromatography. Amino acid composition and the results of limited sequential degradation showed that this peptide corresponds to residues 62 to 98 in the sequence of Konigsberg and co-workers, and contains 2 residues of lysine (Henderson, L., Roy, D., Martin, D., and Konigsberg, W., personal communication). By similar isolation, a second peptide was obtained from unsuccinylated catalytic subunit, containing only the pyridoxylated lysine, which corresponds to Lys-80. Derivatives of catalytic subunit containing an average of either one, two, or three pyridoxamine-P moieties per trimer have been prepared by reduction. These species, which retain catalytic activity in proportion to their unmodified active sites, were recombined with regulatory subunit to prepare partially modified derivatives of native aspartate transcarbamylase. At pH 8, fluorescence emission bands were observed at 340 nm, due to aromatic amino acids in the protein, and at 395 nm, due to the pyridoxamine-P moiety. Upon excitation at 280 nm energy transfer from protein to pyridoxamine-P was approximately 15%. The properties of the probe were used to study changes accompanying the binding of substrates and inhibitors. The effects of CTP and ATP were small. With the transition state analog N-(phosphonacetyl)-L-aspartate (PALA) or the substrate carbamyl-P, two types of response were observed. Derivatives of catalytic subunit and native enzyme which contain some unmodified sites and hence retain partial catalytic activity gave large increases in fluorescence at 395 nm. However, fully modified inactive derivatives gave much smaller increases. A derivative of native enzyme containing one triply modified and one unmodified catalytic subunit behaved like the other partially modified species. These results indicate that there is communication among the active sites of different catalytic trimers in modified native enzyme, as well as among active sites within the same modified catalytic trimer. The increases in fluorescence result from a red shift of the absorption maximum of the pyridoxamine-P moiety from 315 to 325 nm, which increases the absorbance at the excitation wavelength for fluorescence. At pH 7, the absorption spectrum is already shifted and, consequently, the binding of PALA and carbamyl-P has little effect on the fluorescence. Therefore, the binding of these compounds at pH 8.0 must cause a structural change in the protein, which in turn causes protonation of a group in the modified active sites, altering the spectral properties."}
{"id": "PMID:239952", "title": "Hemoglobin Richmond. Subunit dissociation and oxygen equilibrium properties.", "content": "In hemoglobin Richmond (beta102 leads to Lys), amino acid substitution has occurred at the same site as the mutation in hemoglobin Kansas (beta102 Asn leads to Thr), a variant with very low oxygen affinity. Although hemoglobin Richmond has been shown to have increased tetramer-dimer dissociation, its oxygen affinity has been inferred to be normal from studies on hemolysates of carriers. We have isolated hemoglobin Richmond and have further studied its properties. We confirm that the oxygen affinity of pure hemoglobin Richmond under conditions similar to those found in vivo is normal. However, the Bohr effect of the variant hemoglobin is markedly abnormal. Its oxygen affinity is low at high pH and high at low pH, relative to hemoglobin A. The tetramer-dimer equilibrium displays a strong pH dependence such that protons promote dissociation. A model is presented in which the structural change in hemoglobin Richmond results in low oxygen affinity, like hemoglobin Kansas. However, the close linkage between tetramer-dimer dissociation and proton concentration seen with hemoglobin Richmond results in normal oxygen affinity at intracellular pH and hemoglobin concentration, and carriers display no hematological abnormalities.", "contents": "Hemoglobin Richmond. Subunit dissociation and oxygen equilibrium properties. In hemoglobin Richmond (beta102 leads to Lys), amino acid substitution has occurred at the same site as the mutation in hemoglobin Kansas (beta102 Asn leads to Thr), a variant with very low oxygen affinity. Although hemoglobin Richmond has been shown to have increased tetramer-dimer dissociation, its oxygen affinity has been inferred to be normal from studies on hemolysates of carriers. We have isolated hemoglobin Richmond and have further studied its properties. We confirm that the oxygen affinity of pure hemoglobin Richmond under conditions similar to those found in vivo is normal. However, the Bohr effect of the variant hemoglobin is markedly abnormal. Its oxygen affinity is low at high pH and high at low pH, relative to hemoglobin A. The tetramer-dimer equilibrium displays a strong pH dependence such that protons promote dissociation. A model is presented in which the structural change in hemoglobin Richmond results in low oxygen affinity, like hemoglobin Kansas. However, the close linkage between tetramer-dimer dissociation and proton concentration seen with hemoglobin Richmond results in normal oxygen affinity at intracellular pH and hemoglobin concentration, and carriers display no hematological abnormalities."}
{"id": "PMID:239953", "title": "Proton magnetic resonance spectra or porcine muscle adenylate kinase and substrate complexes.", "content": "Porcine muscle adenylate kinase with a molecular weight of 22,000 has 2 histidine, 5 phenylalanine, 7 tyrosine, and no tryptophan residues. The effect of pH, substrate, and the paramagnetic manganous ion on the proton magnetic resonance spectrum of the enzyme, particularly the aromatic region, has been investigated at 220 MHz. The well resolved C2 proton peaks of the 2 histidine residues have been individually assigned to His-36 and His-189 by comparison with the spectrum of the carp muscle enzyme which has only one C2 proton peak and only 1 histidine residue, 36. The chemical shift of the peak designated C2-H of His-36 in the porcine enzyme has a normal titration curve with a pKalpha = 6.3 but the peak for His-189 is not titratable in the pH range 5.8 to 8.1. The pKalpha of the single His-36 of the carp enzyme is similar to that of His-36 of the porcine enzyme. Changes in pH, particularly at low pH, also affect the chemical shifts of the tyrosine residues. Occupation of either the monophosphate site by AMP or the triphosphate site by ATP or GTP causes a downfield shift of the C2-H of His-36, and the equilibrium mixture causes an even greater shift, but no shift in the C2-H of His-189. The substrates also induce changes in the chemical shifts in the phenylalanine-tyrosine region of the spectrum. Tentative assignments of the highest and lowest field peaks in this region have been made based on the three-dimensional structure determined by x-ray crystallography. On the basis of these assignments, it is concluded that Phe-183 is unperturbed by substrate binding but that Tyr-153 or -154 at the hinge of the molecule, are perturbed. The C2-H of adenine and C8-H of adenine or guanine of the bound substrates were also observed; those of AMP are unperturbed but C2-H of ATO is shifted downfield and the C8-H of ATP and GTP are shifted upfield. The paramagnetic manganous ion had no effect on the spectrum at Mn(II) to enzyme ratios below 1:10; above this ratio, a general broadening was observed...", "contents": "Proton magnetic resonance spectra or porcine muscle adenylate kinase and substrate complexes. Porcine muscle adenylate kinase with a molecular weight of 22,000 has 2 histidine, 5 phenylalanine, 7 tyrosine, and no tryptophan residues. The effect of pH, substrate, and the paramagnetic manganous ion on the proton magnetic resonance spectrum of the enzyme, particularly the aromatic region, has been investigated at 220 MHz. The well resolved C2 proton peaks of the 2 histidine residues have been individually assigned to His-36 and His-189 by comparison with the spectrum of the carp muscle enzyme which has only one C2 proton peak and only 1 histidine residue, 36. The chemical shift of the peak designated C2-H of His-36 in the porcine enzyme has a normal titration curve with a pKalpha = 6.3 but the peak for His-189 is not titratable in the pH range 5.8 to 8.1. The pKalpha of the single His-36 of the carp enzyme is similar to that of His-36 of the porcine enzyme. Changes in pH, particularly at low pH, also affect the chemical shifts of the tyrosine residues. Occupation of either the monophosphate site by AMP or the triphosphate site by ATP or GTP causes a downfield shift of the C2-H of His-36, and the equilibrium mixture causes an even greater shift, but no shift in the C2-H of His-189. The substrates also induce changes in the chemical shifts in the phenylalanine-tyrosine region of the spectrum. Tentative assignments of the highest and lowest field peaks in this region have been made based on the three-dimensional structure determined by x-ray crystallography. On the basis of these assignments, it is concluded that Phe-183 is unperturbed by substrate binding but that Tyr-153 or -154 at the hinge of the molecule, are perturbed. The C2-H of adenine and C8-H of adenine or guanine of the bound substrates were also observed; those of AMP are unperturbed but C2-H of ATO is shifted downfield and the C8-H of ATP and GTP are shifted upfield. The paramagnetic manganous ion had no effect on the spectrum at Mn(II) to enzyme ratios below 1:10; above this ratio, a general broadening was observed..."}
{"id": "PMID:239958", "title": "A gas-liquid chromatographic method for the determination of naltrexone and beta-naltrexol in human urine.", "content": "A rapid quantitative method was developed to assay in urine naltrexone and its major urinary metabolite, beta-naltrexol. Following solvent extraction and elimination of interfering materials, the weakly basic drug, its metabolite and the internal standard (etorphine) were silylated and analyzed by gas-liquid chromatography. As little as 0.02 mug/ml of naltrexone and beta-naltrexol was detectable using a hydrogen flame ionization detector. Twenty-four-hour urine samples were analyzed from three subjects taking 180 mg naltrexone daily. The major urinary excretion product was beta-naltrexol which accounted for 48.6% of the administered dose. Only 5% of the administered dose excreted in the urine was naltrexone. Beta-naltrexol was excreted 70% as free drug and 30% conjugated while naltrexone was 90% conjugated.", "contents": "A gas-liquid chromatographic method for the determination of naltrexone and beta-naltrexol in human urine. A rapid quantitative method was developed to assay in urine naltrexone and its major urinary metabolite, beta-naltrexol. Following solvent extraction and elimination of interfering materials, the weakly basic drug, its metabolite and the internal standard (etorphine) were silylated and analyzed by gas-liquid chromatography. As little as 0.02 mug/ml of naltrexone and beta-naltrexol was detectable using a hydrogen flame ionization detector. Twenty-four-hour urine samples were analyzed from three subjects taking 180 mg naltrexone daily. The major urinary excretion product was beta-naltrexol which accounted for 48.6% of the administered dose. Only 5% of the administered dose excreted in the urine was naltrexone. Beta-naltrexol was excreted 70% as free drug and 30% conjugated while naltrexone was 90% conjugated."}
{"id": "PMID:239959", "title": "High-pressure liquid chromatography of drugs. An evaluation of an octadecylsilane stationary phase.", "content": "The performance of a commonly used high-pressure liquid chromatographic stationary phase, octadecylsilane, has been evaluated for 30 compounds selected as representative of a wide variety of drug substances. Chromatographic behavior is found to be highly predictable on the basis of pKa and partition coefficient, and the stationary phase should be especially valuable for the separation of acidic and neutral drugs. For basic drugs, however, the column efficiency is poor, detracting from the overall usefulness.", "contents": "High-pressure liquid chromatography of drugs. An evaluation of an octadecylsilane stationary phase. The performance of a commonly used high-pressure liquid chromatographic stationary phase, octadecylsilane, has been evaluated for 30 compounds selected as representative of a wide variety of drug substances. Chromatographic behavior is found to be highly predictable on the basis of pKa and partition coefficient, and the stationary phase should be especially valuable for the separation of acidic and neutral drugs. For basic drugs, however, the column efficiency is poor, detracting from the overall usefulness."}
{"id": "PMID:239962", "title": "Determination of nanogram amounts of primary aromatic amines and nitro compounds in blood and plasma.", "content": "A rapid and highly sensitive method, based on the direct fluorimetric scanning of thin-layer chromatograms, is described for the quantitative determination of flunitrazepam and its main metabolites in human blood or plasma. This method is generally applicable to aromatic nitro compounds that are reducible with tin(II) chloride. In particular, it is possible to determine primary amines in nanogram amounts. Fluorescamine is used as a regent to produce fluorescent derivatives. The method is suitable for pharmacokinetic studies of flunitrazepam and its main metabolites in human blood and plasma.", "contents": "Determination of nanogram amounts of primary aromatic amines and nitro compounds in blood and plasma. A rapid and highly sensitive method, based on the direct fluorimetric scanning of thin-layer chromatograms, is described for the quantitative determination of flunitrazepam and its main metabolites in human blood or plasma. This method is generally applicable to aromatic nitro compounds that are reducible with tin(II) chloride. In particular, it is possible to determine primary amines in nanogram amounts. Fluorescamine is used as a regent to produce fluorescent derivatives. The method is suitable for pharmacokinetic studies of flunitrazepam and its main metabolites in human blood and plasma."}
{"id": "PMID:239963", "title": "Suppression by thyrotropin-releasing hormone (TRH) of human growth hormone release induced by L-dopa.", "content": "Oral administration of L-dopa (600 mg) significantly raised plasma human growth hormone (hGH) in 6 of 7 normal subjects examined. This L-dopa induced hGH release was significantly suppressed by the intravenous infusion of 1 mg of thyrotropin-releasing hormone (TRH). TRH administration alone had no significant effect on plasma hGH. In contrast, plasma human prolactin (hPRL) consistently increased following TRH infusion. L-dopa significantly lowered basal plasma hPRL levels and also significantly blunted TRH-induced hPRL release. These results suggest that TRH plays an inhibitory role in the regulation of hGH secretion in normal subjects, whereas it stimulates hPRL release.", "contents": "Suppression by thyrotropin-releasing hormone (TRH) of human growth hormone release induced by L-dopa. Oral administration of L-dopa (600 mg) significantly raised plasma human growth hormone (hGH) in 6 of 7 normal subjects examined. This L-dopa induced hGH release was significantly suppressed by the intravenous infusion of 1 mg of thyrotropin-releasing hormone (TRH). TRH administration alone had no significant effect on plasma hGH. In contrast, plasma human prolactin (hPRL) consistently increased following TRH infusion. L-dopa significantly lowered basal plasma hPRL levels and also significantly blunted TRH-induced hPRL release. These results suggest that TRH plays an inhibitory role in the regulation of hGH secretion in normal subjects, whereas it stimulates hPRL release."}
{"id": "PMID:239964", "title": "Studies of the human testis. VII. Conversion of pregnenolone to progesterone.", "content": "Delta5-3beta-Hydroxysteroid dehydrogenase (EC.1.1.1.145) and steroid delta-isomerase (EC.5.3.3.1) were extracted from frozen human testicular tissue and co-precipitated by addition of ammonium sulfate. The activities of both enzymes were localized in the 0-40% (NH4)2SO4 fraction. The enzyme preparation catalyzed conversion of pregnenolone, 17alpha-hydroxypregnenolone, dehydroepiandrosterone, and androstenediol to the corresponding delta4-3-oxosteroid. Since isomerization appeared not to be the rate-limiting step of the overall reaction, measurement of activity of delta5-3beta-hydroxysteroid dehydrogenase was related to the amount of delta4-3-oxosteroid produced from the corresponding delta5-3beta-hydroxysteroid. Delta5-3beta-Hydroxysteroid dehydrogenase required NAD for maximal activity. The Michaelis constants (Km) for NAD were 50 muM, 33 muM and 14 muM, respectively for the dehydrogenation of pregnenolone, 17alpha-hydroxypregnenolone, androstenediol and dehydroepiandrosterone. Km values for each substrate were: pregnenolone 10 muM, 17alpha-hydroxypregnenolone and dehydroepiandrosterone 2.5 muM and androstenediol 3.0 muM. Human testicular delta5-3beta-hydroxysteroid dehydrogenase was inhibited by most of the steroids procued by the testis. The following steroids acted as competitive inhibitors with pregnenolone: 17alpha-hydroxypregenolone (Ki = 1.3 muM), androstenediol (Ki = 2.4 muM), dehydroepiandrosterone (Ki = 0.74 muM), 20alpha-dihydroprogesterone (Ki = 1.1 muM) estrone (Ki = 0.33 muM) and estradiol-17beta (Ki = 0.87 muM). 17alpha-Hydroxyprogesterone, testosterone and androstenedione showed mixed-type inhibition of the enzyme for pregnenolone. Progesterone and NADH were noncompetitive inhibitors of the enzyme for pregnenolone. Ki values, with respect to prenenolone, were 7.4 muM for progesterone and 150 muM for NADH. NADH, however, acted competitively with NAD and Ki value was 30 muM.", "contents": "Studies of the human testis. VII. Conversion of pregnenolone to progesterone. Delta5-3beta-Hydroxysteroid dehydrogenase (EC.1.1.1.145) and steroid delta-isomerase (EC.5.3.3.1) were extracted from frozen human testicular tissue and co-precipitated by addition of ammonium sulfate. The activities of both enzymes were localized in the 0-40% (NH4)2SO4 fraction. The enzyme preparation catalyzed conversion of pregnenolone, 17alpha-hydroxypregnenolone, dehydroepiandrosterone, and androstenediol to the corresponding delta4-3-oxosteroid. Since isomerization appeared not to be the rate-limiting step of the overall reaction, measurement of activity of delta5-3beta-hydroxysteroid dehydrogenase was related to the amount of delta4-3-oxosteroid produced from the corresponding delta5-3beta-hydroxysteroid. Delta5-3beta-Hydroxysteroid dehydrogenase required NAD for maximal activity. The Michaelis constants (Km) for NAD were 50 muM, 33 muM and 14 muM, respectively for the dehydrogenation of pregnenolone, 17alpha-hydroxypregnenolone, androstenediol and dehydroepiandrosterone. Km values for each substrate were: pregnenolone 10 muM, 17alpha-hydroxypregnenolone and dehydroepiandrosterone 2.5 muM and androstenediol 3.0 muM. Human testicular delta5-3beta-hydroxysteroid dehydrogenase was inhibited by most of the steroids procued by the testis. The following steroids acted as competitive inhibitors with pregnenolone: 17alpha-hydroxypregenolone (Ki = 1.3 muM), androstenediol (Ki = 2.4 muM), dehydroepiandrosterone (Ki = 0.74 muM), 20alpha-dihydroprogesterone (Ki = 1.1 muM) estrone (Ki = 0.33 muM) and estradiol-17beta (Ki = 0.87 muM). 17alpha-Hydroxyprogesterone, testosterone and androstenedione showed mixed-type inhibition of the enzyme for pregnenolone. Progesterone and NADH were noncompetitive inhibitors of the enzyme for pregnenolone. Ki values, with respect to prenenolone, were 7.4 muM for progesterone and 150 muM for NADH. NADH, however, acted competitively with NAD and Ki value was 30 muM."}
{"id": "PMID:239965", "title": "Antileukotactic properties of tumor cells.", "content": "A chemotactic factor inactivator (CFI) has been found in extracts of Walker and Novikoff tumor cells maintained in rats. The CFI directly inactivates the bacterial chemotactic factor as well as the leukotactic activity (fro both neutrophils and monocytes) associated with C3 and C5 fragments and with culture fluids of lectin-stimulated lymphoid cells. The inactivation of the bacterial chemotactic factor is temperature and pH dependent. Subcellular fractionation procedures indicate that CFI is largely associated with the microsomal and cytosol fractions of tumor cells. CFI activity is also found in rat neutrophils, alveolar macrophages, and in extracts of liver, spleen, and kidney from normal animals. CFI derived from normal tissues also directly inactivates the bacterial chemotactic factor and has the ability to inactivate chemotactic activity associated with C3 and C5 fragments. A feature of the tumor-associated CFI is its presence in ascitic fluids of animals bearing tumor cells and the relative absence of any CFI activity in acute inflammatory exudates. The finding of the tumor-associated CFI may explain, at least in part, the tendency of malignant tumor cells to suppress cellular inflammatory reactions.", "contents": "Antileukotactic properties of tumor cells. A chemotactic factor inactivator (CFI) has been found in extracts of Walker and Novikoff tumor cells maintained in rats. The CFI directly inactivates the bacterial chemotactic factor as well as the leukotactic activity (fro both neutrophils and monocytes) associated with C3 and C5 fragments and with culture fluids of lectin-stimulated lymphoid cells. The inactivation of the bacterial chemotactic factor is temperature and pH dependent. Subcellular fractionation procedures indicate that CFI is largely associated with the microsomal and cytosol fractions of tumor cells. CFI activity is also found in rat neutrophils, alveolar macrophages, and in extracts of liver, spleen, and kidney from normal animals. CFI derived from normal tissues also directly inactivates the bacterial chemotactic factor and has the ability to inactivate chemotactic activity associated with C3 and C5 fragments. A feature of the tumor-associated CFI is its presence in ascitic fluids of animals bearing tumor cells and the relative absence of any CFI activity in acute inflammatory exudates. The finding of the tumor-associated CFI may explain, at least in part, the tendency of malignant tumor cells to suppress cellular inflammatory reactions."}
{"id": "PMID:239966", "title": "Selective beta-1 receptor blockade with oral practolol in man. A dose-related phenomenon.", "content": "The purpose of this study was to test the hypothesis that oral administration of a low dose of practolol in man produces selective beta-1 receptor blockade, whereas oral administration of a high dose blocks both beta-1 and beta-2 receptors. Normal men were studied 2-4 h after a single oral dose of practolol (1.5 or 12 mg/kg) and after placebo. Effects on beta-1 receptors were studied by measuring heart rate responses to exercise. Effects on beta-2 receptors were tested by measuring forearm vascular responses to brachial arterial infusions of isoproterenol. Neither dose of practolol altered base-line heart rate, forearm vascular resistance, and arterial pressure, Both low and high doses significantly attenuated heart rate responses to exercise. Forearm vasodilator responses to isoproterenol were attenuated by the high dose, but not the low dose, of practolol. Serum concentrations of practolol 2 h after administration of the drug and at the time of the studies of forearm vascular responses averaged 0.5+/-0.1 (SE) and 5.9+/-1.0 mug/ml for low and high doses of practolol, respectively. The results indicate that the phenomenon of selective beta-1 receptor blockade in man is related to the dose and serum concentration of practolol selectively block beta-1 receptors; a high dose and serum concentrations block both beta-1 and beta-2 receptors.", "contents": "Selective beta-1 receptor blockade with oral practolol in man. A dose-related phenomenon. The purpose of this study was to test the hypothesis that oral administration of a low dose of practolol in man produces selective beta-1 receptor blockade, whereas oral administration of a high dose blocks both beta-1 and beta-2 receptors. Normal men were studied 2-4 h after a single oral dose of practolol (1.5 or 12 mg/kg) and after placebo. Effects on beta-1 receptors were studied by measuring heart rate responses to exercise. Effects on beta-2 receptors were tested by measuring forearm vascular responses to brachial arterial infusions of isoproterenol. Neither dose of practolol altered base-line heart rate, forearm vascular resistance, and arterial pressure, Both low and high doses significantly attenuated heart rate responses to exercise. Forearm vasodilator responses to isoproterenol were attenuated by the high dose, but not the low dose, of practolol. Serum concentrations of practolol 2 h after administration of the drug and at the time of the studies of forearm vascular responses averaged 0.5+/-0.1 (SE) and 5.9+/-1.0 mug/ml for low and high doses of practolol, respectively. The results indicate that the phenomenon of selective beta-1 receptor blockade in man is related to the dose and serum concentration of practolol selectively block beta-1 receptors; a high dose and serum concentrations block both beta-1 and beta-2 receptors."}
{"id": "PMID:239967", "title": "Sickling times of individual erythrocytes at zero Po2.", "content": "A rapid-reaction parallel-plate flow channel was used to study the kinetics of erythrocyte sickling upon sudden deoxygenation with sodium dithionite. The erythrocytes were recorded on 16-mm film or video tape and visually tracked in time. Sickling was identified by morphologic criteria. At the flow rate used in these studies, the rate of sickling was a reaction-limited process. There was no loss of cellular deformability or membrane flicker before the onset of sickling. Typical sickling times for sickle (SS) cells and trait (AS) cells at room temperature in isotonic buffer were 2.0 and 70 s, respectively. Increasing the buffer osmolality resulted in shorter sickling times and under hypotonic conditions the time required for sickling was prolonged. Between pH 6.4 and 7.0 there was little change in the time required for 50% of the originally discoidal cells to sickle (t50); whereas a marked increase in t50 occurred between pH 7.4 and 7.6. Whole populations of AS and SS erythrocytes were separated into three fractions after centrifugation. The t50 of the fractions progressively decreased from top to bottom, which paralleled an increase in mean corpuscular hemoglobin concentration (MCHC). The t50 decreased as the temperature was increased from 13 degrees to 34 degrees C. This temperature effect was more pronounced for cells that had osmotically induced reductions in MCHC. A two-step process for erythrocyte sickling is proposed: an initial lag phase, during which there is little or no change in internal viscosity, followed by a rapid phase of cellular deformation. The lag phase is altered by changes in MCHC, pH, and temperature.", "contents": "Sickling times of individual erythrocytes at zero Po2. A rapid-reaction parallel-plate flow channel was used to study the kinetics of erythrocyte sickling upon sudden deoxygenation with sodium dithionite. The erythrocytes were recorded on 16-mm film or video tape and visually tracked in time. Sickling was identified by morphologic criteria. At the flow rate used in these studies, the rate of sickling was a reaction-limited process. There was no loss of cellular deformability or membrane flicker before the onset of sickling. Typical sickling times for sickle (SS) cells and trait (AS) cells at room temperature in isotonic buffer were 2.0 and 70 s, respectively. Increasing the buffer osmolality resulted in shorter sickling times and under hypotonic conditions the time required for sickling was prolonged. Between pH 6.4 and 7.0 there was little change in the time required for 50% of the originally discoidal cells to sickle (t50); whereas a marked increase in t50 occurred between pH 7.4 and 7.6. Whole populations of AS and SS erythrocytes were separated into three fractions after centrifugation. The t50 of the fractions progressively decreased from top to bottom, which paralleled an increase in mean corpuscular hemoglobin concentration (MCHC). The t50 decreased as the temperature was increased from 13 degrees to 34 degrees C. This temperature effect was more pronounced for cells that had osmotically induced reductions in MCHC. A two-step process for erythrocyte sickling is proposed: an initial lag phase, during which there is little or no change in internal viscosity, followed by a rapid phase of cellular deformation. The lag phase is altered by changes in MCHC, pH, and temperature."}
{"id": "PMID:239968", "title": "Pyridine nucleotide-dependent superoxide production by a cell-free system from human granulocytes.", "content": "Using an assay that measured superoxide dismutase-inhibitable nitro blue tetrazolium reduction, we studied superoxide (O2-) production by a cell-free system from human granulocytes. At 40 muM NADPH and a protein concentration of 0.12 mg/ml, lysates prepared from human granulocytes formed O2- at a rate of 18. 4 +/- 4.6 SE nmol/ml reaction mixture per donor, but not with glucose-6-phosphate, 6-phosphogluconate, glyceraldehyde-3-phosphate, sodium lactate, glutathione, or ascorbic acid. The Km's for NADPH and NADH were 8.6 +/- 4.6 muM and 0.83 +/- 0.30 mM, respectively, suggesting that NADPH is the physiological electron donor in this system. O2- production was not inhibited by 1mM KCN. The rate of O2- production by the cell-free system was comparable to the rate of O2-production by an equivalent quantity of intact granulocytes incubated under similar conditions. O2- production by lysates from granulocytes preincubated with serum under conditions previously shown to stimulate O2- production in the intact cells was no different than its production by lysates from unstimulated cells. O2- production at 0.2 mM and 0.02 mM NADPH by lysates from the granulocytes of two patients with chronic granulomatous disease was similar to O2- production by control lysates. This finding was interpreted in terms of the possibility that the metabolic lesion in chronic granulomatous disease may lie outside the oxygen-metabolizing enzyme system of the granulocyte, or alternatively, that the granulocytes may contain two O2- - forming enzymes, one of which is inactive in chronic granulomatous disease.", "contents": "Pyridine nucleotide-dependent superoxide production by a cell-free system from human granulocytes. Using an assay that measured superoxide dismutase-inhibitable nitro blue tetrazolium reduction, we studied superoxide (O2-) production by a cell-free system from human granulocytes. At 40 muM NADPH and a protein concentration of 0.12 mg/ml, lysates prepared from human granulocytes formed O2- at a rate of 18. 4 +/- 4.6 SE nmol/ml reaction mixture per donor, but not with glucose-6-phosphate, 6-phosphogluconate, glyceraldehyde-3-phosphate, sodium lactate, glutathione, or ascorbic acid. The Km's for NADPH and NADH were 8.6 +/- 4.6 muM and 0.83 +/- 0.30 mM, respectively, suggesting that NADPH is the physiological electron donor in this system. O2- production was not inhibited by 1mM KCN. The rate of O2- production by the cell-free system was comparable to the rate of O2-production by an equivalent quantity of intact granulocytes incubated under similar conditions. O2- production by lysates from granulocytes preincubated with serum under conditions previously shown to stimulate O2- production in the intact cells was no different than its production by lysates from unstimulated cells. O2- production at 0.2 mM and 0.02 mM NADPH by lysates from the granulocytes of two patients with chronic granulomatous disease was similar to O2- production by control lysates. This finding was interpreted in terms of the possibility that the metabolic lesion in chronic granulomatous disease may lie outside the oxygen-metabolizing enzyme system of the granulocyte, or alternatively, that the granulocytes may contain two O2- - forming enzymes, one of which is inactive in chronic granulomatous disease."}
{"id": "PMID:239969", "title": "Corticosteroids increase superoxide anion production by rat liver microsomes.", "content": "Superoxide anion production by liver microsomes from intact, adrenalectomized, and cortisoltreated adrenalectomized rats has been determined. The amount formed was roughly proportionate to the amount of cortisol given, and a similar response was seen in the activity of NADPH-cytochrome c reductase. The amount of measurable superoxide anion was markedly reduced by the addition of superoxide dismutase. The increased production of this potent free radical with cortisol therapy suggests that its formation may contribute to some of the harmful effects of corticosteroids given in more than physiologic amounts.", "contents": "Corticosteroids increase superoxide anion production by rat liver microsomes. Superoxide anion production by liver microsomes from intact, adrenalectomized, and cortisoltreated adrenalectomized rats has been determined. The amount formed was roughly proportionate to the amount of cortisol given, and a similar response was seen in the activity of NADPH-cytochrome c reductase. The amount of measurable superoxide anion was markedly reduced by the addition of superoxide dismutase. The increased production of this potent free radical with cortisol therapy suggests that its formation may contribute to some of the harmful effects of corticosteroids given in more than physiologic amounts."}
{"id": "PMID:239970", "title": "Pneumococcus-induced serotonin release from human platelets. Identification of the participating plasma/serum factor as immunoglobulin.", "content": "Pneumococcus-induced serotonin release from human platelets is greatly facilitated by a factor present in normal human plasma and serum. We have identified this factor as immunoglobulin by: (a) removing if from plasma and serum with solid phase antiFab antibody; (b) demonstrating its absence from the serum of an individual with severe immunoglobulin deficiency; and, (c) showing its presence in IgG preparations isolated from normal individuals. Evidence suggesting that the release reaction is triggered by pneumococcal antigen-antibody complexes rather than by nonimmune interaction of immunoglobulin with pneumococcus includes: (a) the failure of isolated IgG myeloma proteins to support release; (b) a lack of correlation between IgG concentration and \"releasing factor activity\" in normal human sera; (c) the identification of a normal serum that supports release by types II and III pneumococci but not type VII; and, (d) the ability of most normal sera to support release by pneumococca serotypes II and VII, though these types have not shown nonimmune reactivity with the Fc portion of the IgG molecule. The ability of antibodies present in normal serum to support pneumococcus-induced serotonin release suggests that the thrombocytopenia seen in pneumococcal infection may at least in part be caused by pneumococcal antigen-antibody complexes.", "contents": "Pneumococcus-induced serotonin release from human platelets. Identification of the participating plasma/serum factor as immunoglobulin. Pneumococcus-induced serotonin release from human platelets is greatly facilitated by a factor present in normal human plasma and serum. We have identified this factor as immunoglobulin by: (a) removing if from plasma and serum with solid phase antiFab antibody; (b) demonstrating its absence from the serum of an individual with severe immunoglobulin deficiency; and, (c) showing its presence in IgG preparations isolated from normal individuals. Evidence suggesting that the release reaction is triggered by pneumococcal antigen-antibody complexes rather than by nonimmune interaction of immunoglobulin with pneumococcus includes: (a) the failure of isolated IgG myeloma proteins to support release; (b) a lack of correlation between IgG concentration and \"releasing factor activity\" in normal human sera; (c) the identification of a normal serum that supports release by types II and III pneumococci but not type VII; and, (d) the ability of most normal sera to support release by pneumococca serotypes II and VII, though these types have not shown nonimmune reactivity with the Fc portion of the IgG molecule. The ability of antibodies present in normal serum to support pneumococcus-induced serotonin release suggests that the thrombocytopenia seen in pneumococcal infection may at least in part be caused by pneumococcal antigen-antibody complexes."}
{"id": "PMID:239974", "title": "Thermodynamic solubility product of human tooth enamel: powdered sample.", "content": "Solubility of human dental enamel in H3PO4 was studied in the pH range of 4.5 to 7.6. Thermodynamic solubility of the enamel mineral was calculated in terms of the ion activity product, (Ca2+)5(PO43-)3(OH-), for hydroxyapatite. The solubility product varied from 7.2 times 10(-53) to 6.4 times 10(-58) mol9 liter-9 depending on the cumulative amount of the dissolution of the solid in a series of repetitive sequences of solubility experiments.", "contents": "Thermodynamic solubility product of human tooth enamel: powdered sample. Solubility of human dental enamel in H3PO4 was studied in the pH range of 4.5 to 7.6. Thermodynamic solubility of the enamel mineral was calculated in terms of the ion activity product, (Ca2+)5(PO43-)3(OH-), for hydroxyapatite. The solubility product varied from 7.2 times 10(-53) to 6.4 times 10(-58) mol9 liter-9 depending on the cumulative amount of the dissolution of the solid in a series of repetitive sequences of solubility experiments."}
{"id": "PMID:239975", "title": "Effect of alpha, alpha'-dipyridyl on the basement membrane of tooth germs in vitro.", "content": "Dipyridyl inhibits the morphogenesis of tooth germs, but the germs recover when transferred to control medium. In this study, the effect of dipyridyl on basement membrane was investigated in vitro. The basal lamina was always present, but the subjacent collagen fibrils disappeared in the presence of dipyridyl and reappeared during recovery in control medium.", "contents": "Effect of alpha, alpha'-dipyridyl on the basement membrane of tooth germs in vitro. Dipyridyl inhibits the morphogenesis of tooth germs, but the germs recover when transferred to control medium. In this study, the effect of dipyridyl on basement membrane was investigated in vitro. The basal lamina was always present, but the subjacent collagen fibrils disappeared in the presence of dipyridyl and reappeared during recovery in control medium."}
{"id": "PMID:239976", "title": "Some properties of uridine 5'-diphosphogalactose: N-acetylglucosamine galactosyltransferase in human parotid saliva.", "content": "Uridine 5'-diphospho (UDP)-galactose: N-acetylglucosamine galactosyltransferase was separated from human parotid saliva and partially purified. The optimum pH of the enzyme was 7.5. The enzyme required a specific acceptor, and its activity was activated by manganese and magnesium ions.", "contents": "Some properties of uridine 5'-diphosphogalactose: N-acetylglucosamine galactosyltransferase in human parotid saliva. Uridine 5'-diphospho (UDP)-galactose: N-acetylglucosamine galactosyltransferase was separated from human parotid saliva and partially purified. The optimum pH of the enzyme was 7.5. The enzyme required a specific acceptor, and its activity was activated by manganese and magnesium ions."}
{"id": "PMID:239989", "title": "Purification and biochemical characterization of rat skin cathepsin D.", "content": "The hemoglobin-hydrolyzing, acidic proteinase activity of rat skin was purified by using ammonium sulfate precipitation. Sephadex G-100 gel column chromatography, acid treatment, and DEAE-cellulose column chromatography, giving a purification coefficient of 182. The pH optimum, molecular size, substrate specificity, as well as inhibitor and activator sensitivity of the enzyme preparation, corresponded closely to those of cathepsin D. The enzyme activity was separated from cathepsin B1. The present status of the knowledge of skin cathespins is reviewed.", "contents": "Purification and biochemical characterization of rat skin cathepsin D. The hemoglobin-hydrolyzing, acidic proteinase activity of rat skin was purified by using ammonium sulfate precipitation. Sephadex G-100 gel column chromatography, acid treatment, and DEAE-cellulose column chromatography, giving a purification coefficient of 182. The pH optimum, molecular size, substrate specificity, as well as inhibitor and activator sensitivity of the enzyme preparation, corresponded closely to those of cathepsin D. The enzyme activity was separated from cathepsin B1. The present status of the knowledge of skin cathespins is reviewed."}
{"id": "PMID:239990", "title": "Enterotoxigenic intestinal bacteria in tropical sprue. III. Preliminary characterization of Klebsiella pneumoniae enterotoxin.", "content": "Cell-free broth filtrates of a strain of Klebsiella pneumoniae serotype 5 retained their capacity to induce fluid secretion in the rabbit ileal loop model after heating (100 C for 30 min), acid treatment (pH 4.4), and dialysis through viscose tubing. Sequential passage of an acetone precipitate of the broth filtrate through Diaflo membranes yielded an active fraction in the UM 2, but not the UM 10, retentate; this observation indicates that the molecular weight of the enterotoxin is in the range of 1,000-10,000. Klebsiella pneumoniae enterotoxin thus resembles the heat-stable enterotoxin of Escherichia coli in a number of respects.", "contents": "Enterotoxigenic intestinal bacteria in tropical sprue. III. Preliminary characterization of Klebsiella pneumoniae enterotoxin. Cell-free broth filtrates of a strain of Klebsiella pneumoniae serotype 5 retained their capacity to induce fluid secretion in the rabbit ileal loop model after heating (100 C for 30 min), acid treatment (pH 4.4), and dialysis through viscose tubing. Sequential passage of an acetone precipitate of the broth filtrate through Diaflo membranes yielded an active fraction in the UM 2, but not the UM 10, retentate; this observation indicates that the molecular weight of the enterotoxin is in the range of 1,000-10,000. Klebsiella pneumoniae enterotoxin thus resembles the heat-stable enterotoxin of Escherichia coli in a number of respects."}
{"id": "PMID:239991", "title": "The effects of Staphylococcus aureus and Klebsiella pneumoniae peritonitis in mice exposed to normal and hypoxic conditions on red cell oxygen transport function.", "content": "Normal mice exposed to 10% oxygen concentration developed a slight but statistically significant decrease in blood pH and a slight statistically insignificant decrease in red cell 2,3-DPG. Mice that were infected intraperitoneally with Staphylococcus aureus or Klebsiella pneumoniae and exposed to 20% oxygen developed acidosis, hemoconcentration, and decreased red cell 2,3-DPG levels. When mice with acute bacterial peritonitis were exposed to 10% oxygen concentration they likewise developed significant acidosis and hemoconcentration, but their reduction in red cell 2,3-DPG was not as great as that in the similarly infected mice exposed to 20% oxygen concentration.", "contents": "The effects of Staphylococcus aureus and Klebsiella pneumoniae peritonitis in mice exposed to normal and hypoxic conditions on red cell oxygen transport function. Normal mice exposed to 10% oxygen concentration developed a slight but statistically significant decrease in blood pH and a slight statistically insignificant decrease in red cell 2,3-DPG. Mice that were infected intraperitoneally with Staphylococcus aureus or Klebsiella pneumoniae and exposed to 20% oxygen developed acidosis, hemoconcentration, and decreased red cell 2,3-DPG levels. When mice with acute bacterial peritonitis were exposed to 10% oxygen concentration they likewise developed significant acidosis and hemoconcentration, but their reduction in red cell 2,3-DPG was not as great as that in the similarly infected mice exposed to 20% oxygen concentration."}
{"id": "PMID:239992", "title": "Renin and arterial pressure in perfused dog kidneys.", "content": "20 isolated dog kidneys were perfused in vitro at 37 degrees C during 6h in a closed circuit system with a Roller pump maintaining a pulsatile flow with a constant output. The perfusate electrolyte concentrations were kept constant. In 12 experiments where a hemodiluted standardized perfusion fluid was used, a significant (0.01 greater than p greater than 0.001) correlation (r = 0.798) was found in the beginning of the experiments between the mean arterial pressure expressed in mm Hg (y) and the renin level, expressed in log U/1 (x): y = 57.0+76.8x. In 4 other experiments, phenoxybenzamine added to the perfusion fluid decreased the arterial pressure but did not prevent the rise of the renin level. In 4 other experiments where the perfusion fluid did not contain blood, renin level and arterial pressure increased, whereas in the experiments using a circuit without a kidney, the renin level did not rise. The possible role of the renin-angiotensin system in causing increased renal vascular resistance during in vitro kidney perfusions is discussed.", "contents": "Renin and arterial pressure in perfused dog kidneys. 20 isolated dog kidneys were perfused in vitro at 37 degrees C during 6h in a closed circuit system with a Roller pump maintaining a pulsatile flow with a constant output. The perfusate electrolyte concentrations were kept constant. In 12 experiments where a hemodiluted standardized perfusion fluid was used, a significant (0.01 greater than p greater than 0.001) correlation (r = 0.798) was found in the beginning of the experiments between the mean arterial pressure expressed in mm Hg (y) and the renin level, expressed in log U/1 (x): y = 57.0+76.8x. In 4 other experiments, phenoxybenzamine added to the perfusion fluid decreased the arterial pressure but did not prevent the rise of the renin level. In 4 other experiments where the perfusion fluid did not contain blood, renin level and arterial pressure increased, whereas in the experiments using a circuit without a kidney, the renin level did not rise. The possible role of the renin-angiotensin system in causing increased renal vascular resistance during in vitro kidney perfusions is discussed."}
{"id": "PMID:239994", "title": "Use of L-rhamnose to study irreversible adsorption of bacteriophage PL-1 to a strain of Lactobacillus casei.", "content": "L-rhamnose has been found to be useful to investigate the process of irreversible adsorption of PL-I phage to its host bacterium, Lactobacillus casei ATCC27092. L-rhamnose inhibited phage adsorption to cells without inactivating free phages. Adsorption inhibition was correlated with the concentrations of L-rhamnose. The inhibitory effect of L-rhamnose on phage adsorption was of a competitive nature against host cells. Among other saccharides tested, L-fucose, L-mannose and D-ribose showed a slight degree of adsorption-inhibiting activity. In early stages of phage adsorption in a tris-maleate buffer, where the binding of phages to cells was still reversible, addition of L-rhamnose resulted in the partial desorption of phages from the cells to which they had adsorbed. However, the number of infective phages desorbed by L-rhamnose treatment gradually fell off as incubation continued, showing that the phages became firmly bound to the cells. Therefore, it is possible to determine the number of phages irreversibly adsorbed to cells by using this desorption technique with L-rhamnose. The process of irreversible phage adsorption, that is, the formation of phage-cell complexes from which no more infective phages could be desorbed, was dependent on temperature and strongly inhibited at 0 degrees C.", "contents": "Use of L-rhamnose to study irreversible adsorption of bacteriophage PL-1 to a strain of Lactobacillus casei. L-rhamnose has been found to be useful to investigate the process of irreversible adsorption of PL-I phage to its host bacterium, Lactobacillus casei ATCC27092. L-rhamnose inhibited phage adsorption to cells without inactivating free phages. Adsorption inhibition was correlated with the concentrations of L-rhamnose. The inhibitory effect of L-rhamnose on phage adsorption was of a competitive nature against host cells. Among other saccharides tested, L-fucose, L-mannose and D-ribose showed a slight degree of adsorption-inhibiting activity. In early stages of phage adsorption in a tris-maleate buffer, where the binding of phages to cells was still reversible, addition of L-rhamnose resulted in the partial desorption of phages from the cells to which they had adsorbed. However, the number of infective phages desorbed by L-rhamnose treatment gradually fell off as incubation continued, showing that the phages became firmly bound to the cells. Therefore, it is possible to determine the number of phages irreversibly adsorbed to cells by using this desorption technique with L-rhamnose. The process of irreversible phage adsorption, that is, the formation of phage-cell complexes from which no more infective phages could be desorbed, was dependent on temperature and strongly inhibited at 0 degrees C."}
{"id": "PMID:239999", "title": "Manipulation of neurotransmitters by acupuncture (?) (A preliminary communication).", "content": "Varying reactions of the vegetative nerve system to various point combinations (for example: vomiting, dizziness, diarrhea, urge to urinate, fatigue or drowsiness, headache), especially to the needling of Tai Chong (Li 3), induced us to perform biochemical studies before and after acupuncture treatment. A group of children and a group of adults were studied. The material studied was urine and blood; from the children, urine only. The following were determined in the urine: indolacetic acid, 5-hydroxy-indol-3-acetic acid, homovanillic acid, and vanillic-mandelic acid; in the blood, tyrosine and tryptophan (free and bound). Individual points with wide influence (He Gu = LI 4; Zu San Li = St 36; Tai Chong = Li 3) and their combination with generally effective points were tested. The needling of Tai Chong especially showed a clear increase in indolamine metabolism. Isolated increases in metabolites of catecholamine metabolism could be correlated with the patient's increased physical activity after acupuncture. Noteworthy is the observation that no significant chemical reactions were evident if local reactions to the needling no longer appeared at the end of a series of acupuncture treatments.", "contents": "Manipulation of neurotransmitters by acupuncture (?) (A preliminary communication). Varying reactions of the vegetative nerve system to various point combinations (for example: vomiting, dizziness, diarrhea, urge to urinate, fatigue or drowsiness, headache), especially to the needling of Tai Chong (Li 3), induced us to perform biochemical studies before and after acupuncture treatment. A group of children and a group of adults were studied. The material studied was urine and blood; from the children, urine only. The following were determined in the urine: indolacetic acid, 5-hydroxy-indol-3-acetic acid, homovanillic acid, and vanillic-mandelic acid; in the blood, tyrosine and tryptophan (free and bound). Individual points with wide influence (He Gu = LI 4; Zu San Li = St 36; Tai Chong = Li 3) and their combination with generally effective points were tested. The needling of Tai Chong especially showed a clear increase in indolamine metabolism. Isolated increases in metabolites of catecholamine metabolism could be correlated with the patient's increased physical activity after acupuncture. Noteworthy is the observation that no significant chemical reactions were evident if local reactions to the needling no longer appeared at the end of a series of acupuncture treatments."}
{"id": "PMID:240009", "title": "Sites of organic acid production and pattern of digesta movement in the gastrointestinal tract of geese.", "content": "Sixteen geese were used to assess the movement of fluid and particulate digesta through their gastrointestinal tracts and to determine the diurnal variation in organic acid levels for the various segments of the tract. Fluid (polyethylene glycol and chronium-labeled ethylenediaminetetraacetic acid) and particulate markers (2 and 5 mm long) were administered with the meal. Animals were killed at given intervals after the administration of markers. The gastrointestinal tract was divided into nine segments for measurement of markers, pH, volatile fatty acids (VFA), and lactic acid contents. The data indicated a rapid evacuation of fluid marker from the foregut (crop, ventriculus, and proventriculus), while particulate markers were retained for extended periods of time. Retention of fluid marker was observed only within the cecum. Retrograde movement of particulate marker was demonstrated from the duodenum to ventriculus and proventriculus. Retrograde movement of fluid marker was observed from the cloaca to the colon, cecum, and distal third of the small intestine. However, particulate marker showed no retrograde movement in these segments of tract. Highest VFA levels were observed in the cecum. Retention of digesta and production of VFA within the colon were less than those noted for the dog, pig and pony. Lactic acid comprised less than 10% of the organic acids present in the gastrointestinal tract and were at their highest levels in the proximal and mid small intestine.", "contents": "Sites of organic acid production and pattern of digesta movement in the gastrointestinal tract of geese. Sixteen geese were used to assess the movement of fluid and particulate digesta through their gastrointestinal tracts and to determine the diurnal variation in organic acid levels for the various segments of the tract. Fluid (polyethylene glycol and chronium-labeled ethylenediaminetetraacetic acid) and particulate markers (2 and 5 mm long) were administered with the meal. Animals were killed at given intervals after the administration of markers. The gastrointestinal tract was divided into nine segments for measurement of markers, pH, volatile fatty acids (VFA), and lactic acid contents. The data indicated a rapid evacuation of fluid marker from the foregut (crop, ventriculus, and proventriculus), while particulate markers were retained for extended periods of time. Retention of fluid marker was observed only within the cecum. Retrograde movement of particulate marker was demonstrated from the duodenum to ventriculus and proventriculus. Retrograde movement of fluid marker was observed from the cloaca to the colon, cecum, and distal third of the small intestine. However, particulate marker showed no retrograde movement in these segments of tract. Highest VFA levels were observed in the cecum. Retention of digesta and production of VFA within the colon were less than those noted for the dog, pig and pony. Lactic acid comprised less than 10% of the organic acids present in the gastrointestinal tract and were at their highest levels in the proximal and mid small intestine."}
{"id": "PMID:240010", "title": "Effects of undernutrition and protein malnutrition on brain chemistry of rats.", "content": "The present study was undertaken to assess the effects of different degrees of nutritional restrictions during fetal life, suckling, and after weaning on the chemical composition of the brain. At 42 days of age, the rats were killed, and the brains were processed for analyses. The rats exposed to severe protein malnutrition after weaning had lower brain weights than those on controls. The brain seems to be resistant to the effects of moderate protein malnutrition imposed during suckling or after weaning. Thus, the brain is either resistant to the effects of mild nutritional deficiency imposed during suckling, or brain composition is very responsive to nutritional rehabilitation initiated after weaning. The effects of severe undernutrition during suckling were not, however, reversed when adequate nutrition was initiated after weaning. The suckling period seems to be critical during development, as the process of myelination was lowered and the levels of electrolytes were irreversibly disturbed. The brains of the rats born to the mothers protein malnourished during gestation were not significantly different from those of controls. The brain seems to be either preferentially protected from the effects of malnutrition imposed during fetal development, or the brain component are very responsive to nutritional rehabilitation initiated immediately after birth. It is suggested that the mother's nutritional status during gestation does not significantly affect the development of the brain. When the young were born to and nursed by protein-malnourished mothers, the growth and the maturation of the brain in such animals were similar to those in rats moderately undernourished during suckling. Growth and maturation of the brain are affected by a lowered level of protein in the diet. Moderate undernutrition imposed during suckling is not important, but the effect is maximum when undernutrition is severe during this period. The suckling period is therefore, comparatively more critical during development.", "contents": "Effects of undernutrition and protein malnutrition on brain chemistry of rats. The present study was undertaken to assess the effects of different degrees of nutritional restrictions during fetal life, suckling, and after weaning on the chemical composition of the brain. At 42 days of age, the rats were killed, and the brains were processed for analyses. The rats exposed to severe protein malnutrition after weaning had lower brain weights than those on controls. The brain seems to be resistant to the effects of moderate protein malnutrition imposed during suckling or after weaning. Thus, the brain is either resistant to the effects of mild nutritional deficiency imposed during suckling, or brain composition is very responsive to nutritional rehabilitation initiated after weaning. The effects of severe undernutrition during suckling were not, however, reversed when adequate nutrition was initiated after weaning. The suckling period seems to be critical during development, as the process of myelination was lowered and the levels of electrolytes were irreversibly disturbed. The brains of the rats born to the mothers protein malnourished during gestation were not significantly different from those of controls. The brain seems to be either preferentially protected from the effects of malnutrition imposed during fetal development, or the brain component are very responsive to nutritional rehabilitation initiated immediately after birth. It is suggested that the mother's nutritional status during gestation does not significantly affect the development of the brain. When the young were born to and nursed by protein-malnourished mothers, the growth and the maturation of the brain in such animals were similar to those in rats moderately undernourished during suckling. Growth and maturation of the brain are affected by a lowered level of protein in the diet. Moderate undernutrition imposed during suckling is not important, but the effect is maximum when undernutrition is severe during this period. The suckling period is therefore, comparatively more critical during development."}
{"id": "PMID:240011", "title": "Effects of early undernutrition and subsequent refeeding on alkaline ribonuclease activity of rat cerebrum and liver.", "content": "The effect of undernutrition and subsequent rehabilitation on free and total alkaline ribonuclease activity (RNase) of cerebrum and liver was studied in 14- and 21-day-old rats. Free RNase activity was higher in both organs at 14 and 21 days of age. However, at day 21 the difference was statistically significant only in liver. Total RNase activity was not changed by undernutrition in cerebrum and was reduced in liver. Nutritional rehabilitation returned both free and total RNase activities to control levels in liver but had no apparent effect on cerebrum. The elevation of free RNase seems to be secondary to a reduced concentration of inhibitor protein and not to de novo synthesis of RNase.", "contents": "Effects of early undernutrition and subsequent refeeding on alkaline ribonuclease activity of rat cerebrum and liver. The effect of undernutrition and subsequent rehabilitation on free and total alkaline ribonuclease activity (RNase) of cerebrum and liver was studied in 14- and 21-day-old rats. Free RNase activity was higher in both organs at 14 and 21 days of age. However, at day 21 the difference was statistically significant only in liver. Total RNase activity was not changed by undernutrition in cerebrum and was reduced in liver. Nutritional rehabilitation returned both free and total RNase activities to control levels in liver but had no apparent effect on cerebrum. The elevation of free RNase seems to be secondary to a reduced concentration of inhibitor protein and not to de novo synthesis of RNase."}
{"id": "PMID:240012", "title": "Demonstration of a specific metabolic effect of dietary disaccharides in the rat.", "content": "Male Wistar rats were starved and refed diets containing either 40% carbohydrate as monosaccharides (glucose, fructose, invert sugar) or disaccharides (maltose, sucrose), or 42.2% carbohydrate as glucose. Induction of various liver enzymes and changes in total liver lipid levels by the different dietary sugars were studied. Liver enzymes measured included glucose-6-phosphate dehydrogenase (g6pd), 6-phosphogluconate dehydrogenase (6PGD), malic enzyme (ME), phosphofructokinase (PFK), L-alpha-glycerol phosphate dehydrogenase (LalphaGPD), pyruvate kinase (PK), citrate cleavage enzyme (CCE), acetyl CoA carboxylase (AcCoAC), and fatty acid synthetase (FAS). The responses in enzyme activity to diets containing glucose or invert sugar were used as the basal response. Enzyme responses to refeeding the carbohydrate diets fell into three categories: (1) enzyme activity increased both by the disaccharide configuration of the carbohydrate and by fructose (G6PD, PK, CCE, AcCoAC, FAS); (2) enzyme activity increased only by the disaccharide configuration of the carbohydrate (6PGD, ME); and (3) enzyme activity increased only by fructose (PFK, LalphaGPD). Total liver lipid level was increased both by the disaccharide configuration of the carbohydrate and by fructose. Refeeding diets containing equal molar amounts of glucose or maltose did not abolish the disaccharide effect. The data indicate that the disaccharide configuration of maltose and sucrose may have an effect at the gastrointestinal level, which causes an increased induction of certain enzymes in the liver.", "contents": "Demonstration of a specific metabolic effect of dietary disaccharides in the rat. Male Wistar rats were starved and refed diets containing either 40% carbohydrate as monosaccharides (glucose, fructose, invert sugar) or disaccharides (maltose, sucrose), or 42.2% carbohydrate as glucose. Induction of various liver enzymes and changes in total liver lipid levels by the different dietary sugars were studied. Liver enzymes measured included glucose-6-phosphate dehydrogenase (g6pd), 6-phosphogluconate dehydrogenase (6PGD), malic enzyme (ME), phosphofructokinase (PFK), L-alpha-glycerol phosphate dehydrogenase (LalphaGPD), pyruvate kinase (PK), citrate cleavage enzyme (CCE), acetyl CoA carboxylase (AcCoAC), and fatty acid synthetase (FAS). The responses in enzyme activity to diets containing glucose or invert sugar were used as the basal response. Enzyme responses to refeeding the carbohydrate diets fell into three categories: (1) enzyme activity increased both by the disaccharide configuration of the carbohydrate and by fructose (G6PD, PK, CCE, AcCoAC, FAS); (2) enzyme activity increased only by the disaccharide configuration of the carbohydrate (6PGD, ME); and (3) enzyme activity increased only by fructose (PFK, LalphaGPD). Total liver lipid level was increased both by the disaccharide configuration of the carbohydrate and by fructose. Refeeding diets containing equal molar amounts of glucose or maltose did not abolish the disaccharide effect. The data indicate that the disaccharide configuration of maltose and sucrose may have an effect at the gastrointestinal level, which causes an increased induction of certain enzymes in the liver."}
{"id": "PMID:240014", "title": "Early versus delayed initiation of continuous negative pressure in infants with hyaline membrane disease.", "content": "Twenty-three infants with HMD of similar severity, who were less than 24 hours of age and who were breathing spontaneously, were divided by random numbers into early and delayed CNP groups. The infants who were treated with CNP before their PaO2 was less than 50 mm Hg while breathing 70% oxygen experienced a significantly greater increase in PaO2 in response to the initiation of CNP, required less time with O2 therapy, required no mechanical ventilation, and had fewer complications. Based on these results, it is suggested that CNP be initiated in infants with HMD, who are less than 24 hours of age and are breathing spontaneously, before the PaO2 becomes less than 50 mm Hg on 70% O2.", "contents": "Early versus delayed initiation of continuous negative pressure in infants with hyaline membrane disease. Twenty-three infants with HMD of similar severity, who were less than 24 hours of age and who were breathing spontaneously, were divided by random numbers into early and delayed CNP groups. The infants who were treated with CNP before their PaO2 was less than 50 mm Hg while breathing 70% oxygen experienced a significantly greater increase in PaO2 in response to the initiation of CNP, required less time with O2 therapy, required no mechanical ventilation, and had fewer complications. Based on these results, it is suggested that CNP be initiated in infants with HMD, who are less than 24 hours of age and are breathing spontaneously, before the PaO2 becomes less than 50 mm Hg on 70% O2."}
{"id": "PMID:240017", "title": "Enhancement of the antitumor effect of 1,3-bis(2-chloroethyl)-1-nitrosourea by various psychotropic drugs in combination with caffeine.", "content": "Certain psychotropic drugs when combined with caffeine significantly enhanced the antitumor effect of 1,3-bis(2-chloroethyl)-1-nitrosourea in murine leukemia L1210. Enhancement required that all three drugs be given together and optimal results were obtained when the psychotropic drug was given 6 hours before 1,3-bis(2-chloroethyl)-1-nitrosourea and caffeine. Thus, 1,3-bis(2-chloroethyl)-1-nitrosourea alone or with caffeine resulted in 5% cures. Addition of chlorpromazine increased the cure rate to 51% while prochlorperazine gave 30% cures. Chlordiazepoxide produced 39% cures while the dibenzazepine compounds studied were ineffective. For the phenothiazine, benzodiazepine and dibenzazepine compounds studied, tentative conclusions could be drawn on the relationship of chemical structure to enhancing activity. For phenothiazines, the substituent in the R2 position of the phenothiazine ring determined activity to a greater extent than did the substituent in the R1 position. For the benzodiazepine compounds, chlordiazepoxide was superior to diazepam. Although the mechanism of action of psychotropic drugs in this system is unknown, these preliminary results suggest the possibility of a change transfer reaction between the free radical form of the psychotropic drug and one or more intracellular constituents.", "contents": "Enhancement of the antitumor effect of 1,3-bis(2-chloroethyl)-1-nitrosourea by various psychotropic drugs in combination with caffeine. Certain psychotropic drugs when combined with caffeine significantly enhanced the antitumor effect of 1,3-bis(2-chloroethyl)-1-nitrosourea in murine leukemia L1210. Enhancement required that all three drugs be given together and optimal results were obtained when the psychotropic drug was given 6 hours before 1,3-bis(2-chloroethyl)-1-nitrosourea and caffeine. Thus, 1,3-bis(2-chloroethyl)-1-nitrosourea alone or with caffeine resulted in 5% cures. Addition of chlorpromazine increased the cure rate to 51% while prochlorperazine gave 30% cures. Chlordiazepoxide produced 39% cures while the dibenzazepine compounds studied were ineffective. For the phenothiazine, benzodiazepine and dibenzazepine compounds studied, tentative conclusions could be drawn on the relationship of chemical structure to enhancing activity. For phenothiazines, the substituent in the R2 position of the phenothiazine ring determined activity to a greater extent than did the substituent in the R1 position. For the benzodiazepine compounds, chlordiazepoxide was superior to diazepam. Although the mechanism of action of psychotropic drugs in this system is unknown, these preliminary results suggest the possibility of a change transfer reaction between the free radical form of the psychotropic drug and one or more intracellular constituents."}
{"id": "PMID:240018", "title": "Site of action and active form of procaine in squid giant axons.", "content": "The active form of procaine and its, site of action on the nerve membrane have been studied in intact and internally perfused squid giant axons. Voltage clamp techniques were employed to measure the masimum values for peak sodium conductance and for steady-state potassium conductance as an index of activity. Changes in internal pH between 7 and 8 do not influence the blocking potency of procaine applied internally. This result, when compared to theoretical curves, is only compatible with the notion that the charged form of procaine present inside is the active form. If one momentarily arrests internal perfusion during an experiment in which procaine is being applied externally, the conductance block is significantly potentiated. When procaine is applied simultaneously to both external and internal phases, most of the block can be reversed by washing out the inside at a time when the outside is still being perfused with procaine. If one reverses this procedure, very little recovery is noted with removal of procaine from the external phase. The rate of recovery from the procaine blockage is much faster in internally perfused axons. These three observations support the notion that procaine acts from inside the nerve membranes. It is concluded that procaine, as other lidocaine derivatives studied previously, acts from the internal nerve membrane surface in the charged form.", "contents": "Site of action and active form of procaine in squid giant axons. The active form of procaine and its, site of action on the nerve membrane have been studied in intact and internally perfused squid giant axons. Voltage clamp techniques were employed to measure the masimum values for peak sodium conductance and for steady-state potassium conductance as an index of activity. Changes in internal pH between 7 and 8 do not influence the blocking potency of procaine applied internally. This result, when compared to theoretical curves, is only compatible with the notion that the charged form of procaine present inside is the active form. If one momentarily arrests internal perfusion during an experiment in which procaine is being applied externally, the conductance block is significantly potentiated. When procaine is applied simultaneously to both external and internal phases, most of the block can be reversed by washing out the inside at a time when the outside is still being perfused with procaine. If one reverses this procedure, very little recovery is noted with removal of procaine from the external phase. The rate of recovery from the procaine blockage is much faster in internally perfused axons. These three observations support the notion that procaine acts from inside the nerve membranes. It is concluded that procaine, as other lidocaine derivatives studied previously, acts from the internal nerve membrane surface in the charged form."}
{"id": "PMID:240019", "title": "On the use of functional antagonism to estimate dissociation constants for beta adrenergic receptor agonists in isolated guinea-pig trachea.", "content": "In guinea-pig trachea, the maximum degree of relaxation that can be elicited by beta adrenergic receptor agonists depends upon the degree of contraction of the smooth muscle induced by cholinergic agonists. In these studies, it is shown that increasing concentrations of carbamylcholine (carbachol) result in a shift to the right of the dose-response curves to (-)-isoproterenol and (-)-soterenol and a reduction of the maximum degree of relaxation produced by these agonists relative to that produced by papaverine. Soterenol is demonstrated to be a partial agonist relative to isoproterenol since its maximum response is reduced to a greater extent by carbachol and it displaces the carbachol dose-response curves to the right less than does isoproterenol. The data were used to calculate, by three different theoretical models of drug-receptor interactions, a dissociation constant (KA) for soterenol. All values obtained were within 2-fold differences. The range of KA values for soterenol was from 5.4 to 9.6 times 10(-8) M. These values are about 100 times larger than the ED50 value for soterenol obtained in the absence of carbachol. The KA value estimated for (-)-isoproterenol (about 3 times 10(-8) M) by one of the models is also around 100 times larger than its ED50 value. This demonstrates further that ED50 values are unreliable indicators of the affinities of agonists for receptors.", "contents": "On the use of functional antagonism to estimate dissociation constants for beta adrenergic receptor agonists in isolated guinea-pig trachea. In guinea-pig trachea, the maximum degree of relaxation that can be elicited by beta adrenergic receptor agonists depends upon the degree of contraction of the smooth muscle induced by cholinergic agonists. In these studies, it is shown that increasing concentrations of carbamylcholine (carbachol) result in a shift to the right of the dose-response curves to (-)-isoproterenol and (-)-soterenol and a reduction of the maximum degree of relaxation produced by these agonists relative to that produced by papaverine. Soterenol is demonstrated to be a partial agonist relative to isoproterenol since its maximum response is reduced to a greater extent by carbachol and it displaces the carbachol dose-response curves to the right less than does isoproterenol. The data were used to calculate, by three different theoretical models of drug-receptor interactions, a dissociation constant (KA) for soterenol. All values obtained were within 2-fold differences. The range of KA values for soterenol was from 5.4 to 9.6 times 10(-8) M. These values are about 100 times larger than the ED50 value for soterenol obtained in the absence of carbachol. The KA value estimated for (-)-isoproterenol (about 3 times 10(-8) M) by one of the models is also around 100 times larger than its ED50 value. This demonstrates further that ED50 values are unreliable indicators of the affinities of agonists for receptors."}
{"id": "PMID:240020", "title": "Distribution of chlorpromazine in the gastrointestinal tract of the rat and its effect on absorptive function.", "content": "The distribution of [14C]chlorpromazine was studied in segments of the gastrointestinal tract of the rat after an oral dose of 20 mg/kg (1-2 muc). The total radioactivity in the gastrointestinal tract was, respectively, 43.2 +/- 3.6, 28.9 +/- 2.2 and 14.1 +/- 1.1 (mean +/- S.E. percent administered dose) at 2, 6 and 24 hours after dosing. The maximum observed total radioactivity in the different segments occurred at different times after dosing. The percentage of total radioactivity present in each tissue as unchanged [14C]chlorpromazine decreased with time in all the tissues. At all time points, this parameter also showed a consistent pattern: % stomach greater than % duodenum greater than % jejunum greater than % ileum. The effect of chronic administration of [14C]chlorpromazine on intestinal absorptive function was studied by the everted sac technique. Mucosal transport of L-[14C]methionine was significantly inhibited (24.4% of control), but no effect on transport of D-[14C]xylose was observed.", "contents": "Distribution of chlorpromazine in the gastrointestinal tract of the rat and its effect on absorptive function. The distribution of [14C]chlorpromazine was studied in segments of the gastrointestinal tract of the rat after an oral dose of 20 mg/kg (1-2 muc). The total radioactivity in the gastrointestinal tract was, respectively, 43.2 +/- 3.6, 28.9 +/- 2.2 and 14.1 +/- 1.1 (mean +/- S.E. percent administered dose) at 2, 6 and 24 hours after dosing. The maximum observed total radioactivity in the different segments occurred at different times after dosing. The percentage of total radioactivity present in each tissue as unchanged [14C]chlorpromazine decreased with time in all the tissues. At all time points, this parameter also showed a consistent pattern: % stomach greater than % duodenum greater than % jejunum greater than % ileum. The effect of chronic administration of [14C]chlorpromazine on intestinal absorptive function was studied by the everted sac technique. Mucosal transport of L-[14C]methionine was significantly inhibited (24.4% of control), but no effect on transport of D-[14C]xylose was observed."}
{"id": "PMID:240022", "title": "Estimation of testosterone and androstenedione in the plasma and testes of cryptorchid offspring of mice treated with oestradiol during pregnancy.", "content": "The injection of pregnant mice with 5 mg oestradiol dipropionate induced a high proportion of bilateral cryptorchidism in the male offspring. The ectopic testes were reduced in size and occupied one of three different positions in the abdomen: pararenal, paravesicular or inguinal. The seminal vesicles were found to be similarly reduced in size whereas the adrenals and pituitaries appeared to be unaffected. The total content of testosterone was reduced in the pararenally placed gonads but was not significantly different from that of the controls when the testes were in the inguinal region. The content of androstenedione was not significantly altered. The concentration of both hormones, however, was increased in all cases. Plasma testosterone levels were lower in all the offspring of treated mothers, especially in those with high ectopia.", "contents": "Estimation of testosterone and androstenedione in the plasma and testes of cryptorchid offspring of mice treated with oestradiol during pregnancy. The injection of pregnant mice with 5 mg oestradiol dipropionate induced a high proportion of bilateral cryptorchidism in the male offspring. The ectopic testes were reduced in size and occupied one of three different positions in the abdomen: pararenal, paravesicular or inguinal. The seminal vesicles were found to be similarly reduced in size whereas the adrenals and pituitaries appeared to be unaffected. The total content of testosterone was reduced in the pararenally placed gonads but was not significantly different from that of the controls when the testes were in the inguinal region. The content of androstenedione was not significantly altered. The concentration of both hormones, however, was increased in all cases. Plasma testosterone levels were lower in all the offspring of treated mothers, especially in those with high ectopia."}
{"id": "PMID:240023", "title": "Potential histamine H2-receptor antagonists. 2. N-alpha-Guanylhistamine.", "content": "The agonist molecule, histamine, has been used as a starting point for the design of potential H2-receptor antagonists. Converting the side-chain amino group into a guanidine yielded the first histamine H2-receptor antagonist, Nalpha-guanylhistamine. Antagonism of H2 receptors was demonstrated by the inhibition of histamine-stimulated gastric acid secretion in the rat at high dose levels (approximate ID50 800 MUmol/kg, iv) and by the inhibition of histamine-stimulated tachycardia of guinea-pig right atrium (pA2 equals 3.9). Guanylhistamine behaves as a partial agonist at histamine H2 receptors.", "contents": "Potential histamine H2-receptor antagonists. 2. N-alpha-Guanylhistamine. The agonist molecule, histamine, has been used as a starting point for the design of potential H2-receptor antagonists. Converting the side-chain amino group into a guanidine yielded the first histamine H2-receptor antagonist, Nalpha-guanylhistamine. Antagonism of H2 receptors was demonstrated by the inhibition of histamine-stimulated gastric acid secretion in the rat at high dose levels (approximate ID50 800 MUmol/kg, iv) and by the inhibition of histamine-stimulated tachycardia of guinea-pig right atrium (pA2 equals 3.9). Guanylhistamine behaves as a partial agonist at histamine H2 receptors."}
{"id": "PMID:240024", "title": "Potential inhibitors of L-asparagine biosynthesis. 3. Aromatic sulfonyl fluoride analogs of L-asparagine and L-glutamine.", "content": "The N-[p-(fluorosulfonyl)benzyl] derivatives of L-asparagine and L-glutamine (1a,b) were synthesized as potential inhibitors of L-asparagine synthetase (ASase). Condensation of p-(fluorosulfonyl)benzylamine (2) with the suitably protected amino acid in the presence of dicyclohexylcarbodiimide, followed by deblocking, afforded 1a and 1b. Derivatives 1a and 1b at 10 mM inhibit ASase isolated from Novikoff hepatoma (rats) by 60 and 46%, respectively. Preliminary results on inhibition of Jensen sarcoma (L-asparaginase sensitive) and JA-1 sarcoma (L-asparaginase resistant) tissue cultures by 0.3 mM 1a (139,90%) and 1b (101, 103%), respectively, are discussed.", "contents": "Potential inhibitors of L-asparagine biosynthesis. 3. Aromatic sulfonyl fluoride analogs of L-asparagine and L-glutamine. The N-[p-(fluorosulfonyl)benzyl] derivatives of L-asparagine and L-glutamine (1a,b) were synthesized as potential inhibitors of L-asparagine synthetase (ASase). Condensation of p-(fluorosulfonyl)benzylamine (2) with the suitably protected amino acid in the presence of dicyclohexylcarbodiimide, followed by deblocking, afforded 1a and 1b. Derivatives 1a and 1b at 10 mM inhibit ASase isolated from Novikoff hepatoma (rats) by 60 and 46%, respectively. Preliminary results on inhibition of Jensen sarcoma (L-asparaginase sensitive) and JA-1 sarcoma (L-asparaginase resistant) tissue cultures by 0.3 mM 1a (139,90%) and 1b (101, 103%), respectively, are discussed."}
{"id": "PMID:240025", "title": "Chemical differentiation of histamine H1- and H2-receptor agonists.", "content": "Histamine exists predominantly as the NT-H tautomer of the monocation (IIa) at a physiological pH of 7.4 and structure-activity studies indicate that this tautomer is likely to be the pharmacologically active species for both H1 and H2 receptors. Effective H2-receptor agonists appear to require a prototropic tautomeric system whereas H1-receptor agonists do not need to be tautomeric. This identifies a chemical difference in the receptor requirements which provides the basis for obtaining selective histamine H1-receptor agonists. Thus 2-(2-aminoethyl)thiazole and 2-(2-aminoethyl)pyridine are nontautomeric and are highly selective agonists for histamine H1 receptors (H1:H2 ca. 90:1 and 30:1, respectively). In conjunction with the selective H2-receptor agonist, 4-methylhistamine, they are of great value for studying the pharmacology of histamine receptors.", "contents": "Chemical differentiation of histamine H1- and H2-receptor agonists. Histamine exists predominantly as the NT-H tautomer of the monocation (IIa) at a physiological pH of 7.4 and structure-activity studies indicate that this tautomer is likely to be the pharmacologically active species for both H1 and H2 receptors. Effective H2-receptor agonists appear to require a prototropic tautomeric system whereas H1-receptor agonists do not need to be tautomeric. This identifies a chemical difference in the receptor requirements which provides the basis for obtaining selective histamine H1-receptor agonists. Thus 2-(2-aminoethyl)thiazole and 2-(2-aminoethyl)pyridine are nontautomeric and are highly selective agonists for histamine H1 receptors (H1:H2 ca. 90:1 and 30:1, respectively). In conjunction with the selective H2-receptor agonist, 4-methylhistamine, they are of great value for studying the pharmacology of histamine receptors."}
{"id": "PMID:240032", "title": "Calcium ion-dependent phosphorylation of human erythrocyte membranes.", "content": "Calcium ions promote the rapid transfer of the terminal phosphate of ATP to a protein of human erythrocyte membranes. The concentration of Ca2+ for half-maximal effect is 7 muM. At nonlimiting ATP concentrations the level of 32P incorporated by the membranes is independent of the presence or absence of Mg2+. The number of phosphorylating sites in a single erythrocyte membrane is about 700. The influence of pH on the rate of hydrolysis of the bound phosphate and its rapid release on exposure to hydroxylamine are both consistent with an acylphosphate bond. The phosphate in the protein undergoes rapid turnover. Enzymatic splitting of the phosphate is stimulated by Mg2+ but not by Ca2+. It is proposed that Mg2+ accelerates the splitting of the phosphate by favoring the conversion of the phosphoprotein from a state of low reactivity to a state of high reactivity towards water. The reactions described probably are intermediate steps in the hydrolysis of ATP catalyzed by the Ca2+-dependent ATPase of human erythrocyte membranes.", "contents": "Calcium ion-dependent phosphorylation of human erythrocyte membranes. Calcium ions promote the rapid transfer of the terminal phosphate of ATP to a protein of human erythrocyte membranes. The concentration of Ca2+ for half-maximal effect is 7 muM. At nonlimiting ATP concentrations the level of 32P incorporated by the membranes is independent of the presence or absence of Mg2+. The number of phosphorylating sites in a single erythrocyte membrane is about 700. The influence of pH on the rate of hydrolysis of the bound phosphate and its rapid release on exposure to hydroxylamine are both consistent with an acylphosphate bond. The phosphate in the protein undergoes rapid turnover. Enzymatic splitting of the phosphate is stimulated by Mg2+ but not by Ca2+. It is proposed that Mg2+ accelerates the splitting of the phosphate by favoring the conversion of the phosphoprotein from a state of low reactivity to a state of high reactivity towards water. The reactions described probably are intermediate steps in the hydrolysis of ATP catalyzed by the Ca2+-dependent ATPase of human erythrocyte membranes."}
{"id": "PMID:240033", "title": "Loss of marrow allograft resistance in mice with transplanted methylcholanthrene-induced sarcomas.", "content": "To determine if the effector cells responsible for allogeneic marrow stem cell rejections were suppressed in mice with tumors, C57BL/6 (B6) mice were inoculated with 3-methylcholanthrene (MCA)-induced sarcoma cells. When the tumor reached 2.0--2.5 cm in diameter, these mice and control B6 and (BALB/c times A)F1 (CAF1) uninoculated animals were irradiated and given BALB/c marrow cells in the first of a two-step \"stem cell rescue\" experiment. Four days later, spleen cells of the primary hosts were reinoculated into irradiated CAF1 secondary hosts compatible with BALB/c marrow cells and immunized against B6 antigens. Splenic uptake (percent) of 125I-5-iodo-2'-deoxyuridine 5 days after spleen cell regrafting was used as a measure of cell proliferation and reflected growth of the stem cells in the primary hosts. BALB/c stem cells grew as well in B6 mice with tumors as in CAF1 primary hosts but were rejected by B6 controls. Seeding efficiency of BALB/c stem cells 6 hours after infusion of marrow cells and growth of syngeneic B6 stem cells were enhanced twofold in spleens of tumor-bearing B6 mice. To exclude the possibility that enhanced seeding resulted in greater survival of allogeneic stem cells, more DBA/2 marrow cells were infused into control B6 primary hosts than into tumor-bearing B6 and control DBA/2 mice. Control B6 mice resisted growth of even 7.5 times 10(6) DBA/2 marrow cells, whereas B6 tumor bearers allowed growth of 2.5 times 10(6) cells. No \"suppressor cells\" capable of inhibiting marrow cell allograft reactions were detected in spleens of tumor-bearing mice. Thus transplanted syngeneic MCA-induced sarcomas abrogated the ability of mice to reject allogeneic marrow stem cells.", "contents": "Loss of marrow allograft resistance in mice with transplanted methylcholanthrene-induced sarcomas. To determine if the effector cells responsible for allogeneic marrow stem cell rejections were suppressed in mice with tumors, C57BL/6 (B6) mice were inoculated with 3-methylcholanthrene (MCA)-induced sarcoma cells. When the tumor reached 2.0--2.5 cm in diameter, these mice and control B6 and (BALB/c times A)F1 (CAF1) uninoculated animals were irradiated and given BALB/c marrow cells in the first of a two-step \"stem cell rescue\" experiment. Four days later, spleen cells of the primary hosts were reinoculated into irradiated CAF1 secondary hosts compatible with BALB/c marrow cells and immunized against B6 antigens. Splenic uptake (percent) of 125I-5-iodo-2'-deoxyuridine 5 days after spleen cell regrafting was used as a measure of cell proliferation and reflected growth of the stem cells in the primary hosts. BALB/c stem cells grew as well in B6 mice with tumors as in CAF1 primary hosts but were rejected by B6 controls. Seeding efficiency of BALB/c stem cells 6 hours after infusion of marrow cells and growth of syngeneic B6 stem cells were enhanced twofold in spleens of tumor-bearing B6 mice. To exclude the possibility that enhanced seeding resulted in greater survival of allogeneic stem cells, more DBA/2 marrow cells were infused into control B6 primary hosts than into tumor-bearing B6 and control DBA/2 mice. Control B6 mice resisted growth of even 7.5 times 10(6) DBA/2 marrow cells, whereas B6 tumor bearers allowed growth of 2.5 times 10(6) cells. No \"suppressor cells\" capable of inhibiting marrow cell allograft reactions were detected in spleens of tumor-bearing mice. Thus transplanted syngeneic MCA-induced sarcomas abrogated the ability of mice to reject allogeneic marrow stem cells."}
{"id": "PMID:240035", "title": "Influence of allogeneic effect on 7,12-dimethylbenz(alpha)anthracene carcinogenesis in mice.", "content": "Charles River mice either untreated or treated at birth with 7,12-dimethylbenz]alpha[anthracene (DMBA) were given allogeneic spleen cells from adult C57BL/Cas donors. These spleen cells were given as a single injection to mice at birth or at 7 or 14 days of age. Allogeneic treatment of mice at birth significantly increased the incidence of DMBA-induced lymphomas and shortened the latency period of the tumors. The incidence of subcutaneous tumors was moderately increased in DMBA-treated mice given grafts of allogeneic cells at 7 days of age. Lung tumors appeared to be decreased in the group given DMBA at birth and allogeneic cells 14 days later. Treatment with only allogeneic cells gave results essentially similar to those observed in untreated controls.", "contents": "Influence of allogeneic effect on 7,12-dimethylbenz(alpha)anthracene carcinogenesis in mice. Charles River mice either untreated or treated at birth with 7,12-dimethylbenz]alpha[anthracene (DMBA) were given allogeneic spleen cells from adult C57BL/Cas donors. These spleen cells were given as a single injection to mice at birth or at 7 or 14 days of age. Allogeneic treatment of mice at birth significantly increased the incidence of DMBA-induced lymphomas and shortened the latency period of the tumors. The incidence of subcutaneous tumors was moderately increased in DMBA-treated mice given grafts of allogeneic cells at 7 days of age. Lung tumors appeared to be decreased in the group given DMBA at birth and allogeneic cells 14 days later. Treatment with only allogeneic cells gave results essentially similar to those observed in untreated controls."}
{"id": "PMID:240036", "title": "Utilization of supervised physician's assistants in emergency room coverage in a small rural community hospital.", "content": "A study has been made of an initial 2-year experience in a 90-bed rural community hospital where emergency room primary coverage has been provided by Physician's Assistants under supervision of specialists in the field of general surgery, pediatrics, and internal medicine. Emphasis has been placed on a rigidly supervised program as well as physician supervision and availability on a patient-call basis. This supervision may take the form of immediate availability of the physician to the emergency room, telephone consultation or, in minor illnesses and injuries, continued review of the record of each individual patient seen by the Physician's Assistant. A review of the most recent 2-month ER-OPD experience showed that in a small rural hospital, a majority (62%) of the patients had an illness or injury of a minor, nonserious degree which could be handled primarily by a Physician's Assistant. This has led to emergency room care which has been judged by the patients, the emergency-room nurses, and the supervising physicians to be more efficient and prompt than had been previously provided, yet not reduced in quality. The program described was developed by physicians active in private practice working with the Physician's Assistants and RN's in the ER-OPD. The physicians' time spent in teaching, supervision and development of written policy was great, and, at times, threatened the continuation of the program. A fulltime physician in the hospital could better initiate the program of teaching, supervision, formulating written procedures, and establishing policies with different specialist.", "contents": "Utilization of supervised physician's assistants in emergency room coverage in a small rural community hospital. A study has been made of an initial 2-year experience in a 90-bed rural community hospital where emergency room primary coverage has been provided by Physician's Assistants under supervision of specialists in the field of general surgery, pediatrics, and internal medicine. Emphasis has been placed on a rigidly supervised program as well as physician supervision and availability on a patient-call basis. This supervision may take the form of immediate availability of the physician to the emergency room, telephone consultation or, in minor illnesses and injuries, continued review of the record of each individual patient seen by the Physician's Assistant. A review of the most recent 2-month ER-OPD experience showed that in a small rural hospital, a majority (62%) of the patients had an illness or injury of a minor, nonserious degree which could be handled primarily by a Physician's Assistant. This has led to emergency room care which has been judged by the patients, the emergency-room nurses, and the supervising physicians to be more efficient and prompt than had been previously provided, yet not reduced in quality. The program described was developed by physicians active in private practice working with the Physician's Assistants and RN's in the ER-OPD. The physicians' time spent in teaching, supervision and development of written policy was great, and, at times, threatened the continuation of the program. A fulltime physician in the hospital could better initiate the program of teaching, supervision, formulating written procedures, and establishing policies with different specialist."}
{"id": "PMID:240037", "title": "Polyacrylamide gel electrophoresis of intact bacteriophage T4D particles.", "content": "A method for the electrophoresis of intact bacteriophage T4D particles through polyacrylamide gels has been developed. It was found that phage particles will migrate through dilute polyacrylamide gels (less than 2.1%) in the presence of a low concentration of MgCl2. As few as 5 x 10(9) phage particles can be seen directly as a light-scattering band during the course of electrophoresis. The band can also be detected by scanning gels at 260 to 265 nm or by eluting viable phage particles from gel slices. A new mutant (eph1) has been identified on the basis of its decreased electrophoretic mobility compared with that of the wild type; mutant particles migrated 14% slower than the wild type particles at pH 8.3 and 35% slower at pH 5.0. The isoelectric points of both the wild type and eph1 mutant were found to be between pH 4.0 and 5.0. Particles of T4 with different head lengths were also studied. Petite particles (heads 20% shorter than normal) migrated at the same rate as normal-size particles. Giant particles, heterogenous with respect to head length (two to nine times normal), migrated faster than normal-size particles as a diffuse band. This diffuseness was due to separation within the band of particles having mobilities ranging from 8 to 35% faster than those of normal-size particles. These observations extend the useful range of polyacrylamide gel electrophoresis to include much larger particles than have previously been studied, including most viruses.", "contents": "Polyacrylamide gel electrophoresis of intact bacteriophage T4D particles. A method for the electrophoresis of intact bacteriophage T4D particles through polyacrylamide gels has been developed. It was found that phage particles will migrate through dilute polyacrylamide gels (less than 2.1%) in the presence of a low concentration of MgCl2. As few as 5 x 10(9) phage particles can be seen directly as a light-scattering band during the course of electrophoresis. The band can also be detected by scanning gels at 260 to 265 nm or by eluting viable phage particles from gel slices. A new mutant (eph1) has been identified on the basis of its decreased electrophoretic mobility compared with that of the wild type; mutant particles migrated 14% slower than the wild type particles at pH 8.3 and 35% slower at pH 5.0. The isoelectric points of both the wild type and eph1 mutant were found to be between pH 4.0 and 5.0. Particles of T4 with different head lengths were also studied. Petite particles (heads 20% shorter than normal) migrated at the same rate as normal-size particles. Giant particles, heterogenous with respect to head length (two to nine times normal), migrated faster than normal-size particles as a diffuse band. This diffuseness was due to separation within the band of particles having mobilities ranging from 8 to 35% faster than those of normal-size particles. These observations extend the useful range of polyacrylamide gel electrophoresis to include much larger particles than have previously been studied, including most viruses."}
{"id": "PMID:240038", "title": "Studies of introital colonization in women with recurrent urinary infections. I. The role of vaginal pH.", "content": "The pH of the vaginal introitus was compared to quantitative cultures of the introital mucosa (Escherichia coli, Proteus mirabilis and Streptococcus faecalis) in 800 samples. Introital carriage of more than 100 bacteria per ml. was significantly greater at pH of more than 4.4 (p less than 0.005) when compared to mucosal pH of less than or equal to 4.4.", "contents": "Studies of introital colonization in women with recurrent urinary infections. I. The role of vaginal pH. The pH of the vaginal introitus was compared to quantitative cultures of the introital mucosa (Escherichia coli, Proteus mirabilis and Streptococcus faecalis) in 800 samples. Introital carriage of more than 100 bacteria per ml. was significantly greater at pH of more than 4.4 (p less than 0.005) when compared to mucosal pH of less than or equal to 4.4."}
{"id": "PMID:240039", "title": "Studies of introital colonization in women with recurrent urinary infections. II. A comparison of growth in normal vaginal fluid of common versus uncommon serogroups of Escherichia coli.", "content": "Vaginal fluid collected from volunteers who denied a history of urinary infections was bactericidal to Escherichia coli at pH 4.0. When the pH was increased to 6.5 with sodium hydroxide, the same vaginal fluids supported bacterial growth. If vaginal fluid was adjusted at pH increments between 4.0 and 5.0, and inoculated with common and uncommon serogroups of Escherichia coli, the uncommon O-groups that never cause urinary infections were significantly (p less than 0.005) more inhibited by the lower vaginal pH than were the common O-groups of Escherichia coli.", "contents": "Studies of introital colonization in women with recurrent urinary infections. II. A comparison of growth in normal vaginal fluid of common versus uncommon serogroups of Escherichia coli. Vaginal fluid collected from volunteers who denied a history of urinary infections was bactericidal to Escherichia coli at pH 4.0. When the pH was increased to 6.5 with sodium hydroxide, the same vaginal fluids supported bacterial growth. If vaginal fluid was adjusted at pH increments between 4.0 and 5.0, and inoculated with common and uncommon serogroups of Escherichia coli, the uncommon O-groups that never cause urinary infections were significantly (p less than 0.005) more inhibited by the lower vaginal pH than were the common O-groups of Escherichia coli."}
{"id": "PMID:240040", "title": "Studies of introital colonization in women with recurrent urinary infections. III. Vaginal glycogen concentrations.", "content": "The concentration of glycogen in vaginal fluid was measured in 37 samples from 6 volunteers without urinary infections and in 96 samples from 12 patients with recurrent urinary infections. The mean glycogen concentrations, 440 mug. per ml. from the controls and 564 mug. per ml. from the patients, were not statistically different (p more than 0.05). Although an introital pH more than or equal to 4.4 was associated with low concentrations of glycogen in vaginal fluid, a pH less than 4.4 was found with high and low glycogen concentration. Sodium concentration was statistically higher in vaginal fluid from patients compared to controls (p less than 0.01) while potassium concentration was the same in both groups.", "contents": "Studies of introital colonization in women with recurrent urinary infections. III. Vaginal glycogen concentrations. The concentration of glycogen in vaginal fluid was measured in 37 samples from 6 volunteers without urinary infections and in 96 samples from 12 patients with recurrent urinary infections. The mean glycogen concentrations, 440 mug. per ml. from the controls and 564 mug. per ml. from the patients, were not statistically different (p more than 0.05). Although an introital pH more than or equal to 4.4 was associated with low concentrations of glycogen in vaginal fluid, a pH less than 4.4 was found with high and low glycogen concentration. Sodium concentration was statistically higher in vaginal fluid from patients compared to controls (p less than 0.01) while potassium concentration was the same in both groups."}
{"id": "PMID:240041", "title": "Tissue invasion by unnamed marine vibrios.", "content": "Vibrio parahaemolyticus is an extremely common organism of major importance as a cause of gastroenteritis, but not common as a cause of tissue infection. Of three patients who had serious localized tissue infections, one died because of an unnamed marine Vibrio infection. Vibrios are easily isolated, although their final speciation is quite difficult in view of their unsettled taxonomic position. It is hoped that agreement can be reached as to bacteriologic genealogy; perhaps then the specific pathogenic manifestations will be clarified. The clinician should consider the possibility of this pathogen in any patient with a wound related to saltwater or seafood.", "contents": "Tissue invasion by unnamed marine vibrios. Vibrio parahaemolyticus is an extremely common organism of major importance as a cause of gastroenteritis, but not common as a cause of tissue infection. Of three patients who had serious localized tissue infections, one died because of an unnamed marine Vibrio infection. Vibrios are easily isolated, although their final speciation is quite difficult in view of their unsettled taxonomic position. It is hoped that agreement can be reached as to bacteriologic genealogy; perhaps then the specific pathogenic manifestations will be clarified. The clinician should consider the possibility of this pathogen in any patient with a wound related to saltwater or seafood."}
{"id": "PMID:240045", "title": "Long-term prognosis of renovascular hypertension: comparative study in operated and non-operated patients.", "content": "Long-term prognosis of renovascular hypertension has been studied in 56 patients. Twenty-nine patients underwent surgical treatment and 27 patients were not operated upon for various reason. Initial severity of hypertension in the operated group was nearly comparable to that of the non-operated group. Average of observation periods in each group is 5.8 and 5.9 years respectively, and the longest follow-up period has been up to 12 years. Hypertension cured or improved in 25 cases of the operated group. Antihypertensive therapy was effective in 7 of the medically treated patients. During the entire observation periods, 2 cases of the operated and 10 cases of the non-operated group died. Seven deaths of the non-operated group seemed to be causally related to hypertension. It is concluded that long-term prognosis of operated patients is significantly improved as compared with that of patients whose renovascular hypertension could not be treated surgically. Prevelence of aortitis (Takayasu's disease) as a cause of renovascular hypertension is a particular problem in our series because extensive and complicated renovascular lesions may make surgical intervention difficult in some patients.", "contents": "Long-term prognosis of renovascular hypertension: comparative study in operated and non-operated patients. Long-term prognosis of renovascular hypertension has been studied in 56 patients. Twenty-nine patients underwent surgical treatment and 27 patients were not operated upon for various reason. Initial severity of hypertension in the operated group was nearly comparable to that of the non-operated group. Average of observation periods in each group is 5.8 and 5.9 years respectively, and the longest follow-up period has been up to 12 years. Hypertension cured or improved in 25 cases of the operated group. Antihypertensive therapy was effective in 7 of the medically treated patients. During the entire observation periods, 2 cases of the operated and 10 cases of the non-operated group died. Seven deaths of the non-operated group seemed to be causally related to hypertension. It is concluded that long-term prognosis of operated patients is significantly improved as compared with that of patients whose renovascular hypertension could not be treated surgically. Prevelence of aortitis (Takayasu's disease) as a cause of renovascular hypertension is a particular problem in our series because extensive and complicated renovascular lesions may make surgical intervention difficult in some patients."}
{"id": "PMID:240047", "title": "[Comparison of the antibacterial activity of amikacin (BB-K8) with other aminoglycosides against pathogens recently isolated from clinical materials (author's transl) ].", "content": "We determined the antibacterial activity of amikacin against 1,277 strains of pathogenic bacteria isolated from clinical materials during 1974, including beta hemolytic streptococci, pneumococci, enterococci, Staphylococcus aureus, Staph. epidermidis, Escherichia coli, Klebsiella, Enterobacter, Citrobacter, Serratia, Proteus morganii and Pseudomonas aeruginosa, and compared the minimum inhibitory concentration (MIC) of this drug with gentamicin, dibekacin, tobramycin and kanamycin. 1)Antibacterial activity of amikacin against beta hemolytic streptococci, pneumococci and enterococci was as weak as the other four aminoglycosides, but against Staph. aureus, Staph. epidermidis, various groups of Enterobacteriaceae and Pseudomonas aeruginosa showed amikacin the good antibacterial activity as gentamicin, dibedacin and tobramycin, and also showed the good activity against kanamycin resistant strains. 2) Amikacin has the similar antibacterial spectrum as gentamicin, dibekacin or tobramycin, but its antibacterial activity is generally weakest among these four drugs. 3) On many strains tested the cross resistance is observed between amikacin and one of gentamicin, dibekacin and tobramycin, but several strains of Proteus morganii and Pseudomonas aeruginosa which have rather large MIC against gentamicin, dibekacin or tobramycin showed rather small MIC against amikacin.", "contents": "[Comparison of the antibacterial activity of amikacin (BB-K8) with other aminoglycosides against pathogens recently isolated from clinical materials (author's transl) ]. We determined the antibacterial activity of amikacin against 1,277 strains of pathogenic bacteria isolated from clinical materials during 1974, including beta hemolytic streptococci, pneumococci, enterococci, Staphylococcus aureus, Staph. epidermidis, Escherichia coli, Klebsiella, Enterobacter, Citrobacter, Serratia, Proteus morganii and Pseudomonas aeruginosa, and compared the minimum inhibitory concentration (MIC) of this drug with gentamicin, dibekacin, tobramycin and kanamycin. 1)Antibacterial activity of amikacin against beta hemolytic streptococci, pneumococci and enterococci was as weak as the other four aminoglycosides, but against Staph. aureus, Staph. epidermidis, various groups of Enterobacteriaceae and Pseudomonas aeruginosa showed amikacin the good antibacterial activity as gentamicin, dibedacin and tobramycin, and also showed the good activity against kanamycin resistant strains. 2) Amikacin has the similar antibacterial spectrum as gentamicin, dibekacin or tobramycin, but its antibacterial activity is generally weakest among these four drugs. 3) On many strains tested the cross resistance is observed between amikacin and one of gentamicin, dibekacin and tobramycin, but several strains of Proteus morganii and Pseudomonas aeruginosa which have rather large MIC against gentamicin, dibekacin or tobramycin showed rather small MIC against amikacin."}
{"id": "PMID:240048", "title": "[Chemotherapy of purulent meningitis in children (author's transl)].", "content": "Purulent meningitis in patients admitted to the pediatric department of Kyoto University Hospital and affiliated institutions from 1951 through 1973 were studied with emphasis on the kinds of the causative organisms and the susceptibility of these organisms to antibiotics. The findings in this study have served to help select antibiotics most likely to be effective against this disease. The overall incidence of purulent meningitis was 0.68%. This figure decreased little throughout the period. As for the frequency of causative organisms, Neisseria meningitidis led the list, and Diplococcus pneumoniae ranked just behind. Haemophilus influenzae was rare. The frequency of N. meningitidis, however, decreased sharply in spite of the essentially unchanged overall incidence of this disease. The probable reason for the poor prognosis of this disease in spite of the remarkable strides in chemotherapy is the decreased frequency of N. meningitidis and the inversely increased organisms that are resistant to usual chemotherapy. The therapeutic effectiveness of cefazolin against this disease was studied in 15 children including eight newborns and four infants. The daily per kg bodyweight dose was 50 mg or less in four, 50 approximately 100 mg in five, and more than 100 mg in the remaining six. The route of administration was either intramuscular or intravenous. No deaths occurred. The rate of effectiveness was as high as 80%. Residual symptoms were recorded in six and, in as many as five of them, the cause was a-tributable to the delayed detection of the disease. Neither side effects nor aberrent laboratory findings attributable to large doses of cefazolin were recorded. Diffusibility of cefazolin into the CSF was studied in nine subjects. The CSF concentration of this antibiotic was shown to be somewhat lower than that of ampicillin or cephaloridine and to account on an average for 13% of the mean peak serum level. This relatively low diffusibility will be offset by its high serum concentration and safe large-dose therapy. These findings have clearly shown that the therapeutic effectiveness of cefazolin is as high as that of ampicillin, and that this excellent effectiveness holds true even when the causative organism happens to be Escherichia coli, Klebsiella, etc. that are resistant to ampicillin. The authors have furthermore scrutinized much literature on the frequency of the causative organisms, emergence of resistant strains, and the diffusibility of antibiotics into the CSF, and arrived at the conclusion that cefazolin is a promising antibiotic of choice for the treatment of purulent meningitis in newborn. The daily dose is preferably 150 mg/kg or more given in three divided intravenous doses. Meanwhile ampicillin proved to be useful as the antibiotic of choice for the treatment of purulent meningitis in infants and children.", "contents": "[Chemotherapy of purulent meningitis in children (author's transl)]. Purulent meningitis in patients admitted to the pediatric department of Kyoto University Hospital and affiliated institutions from 1951 through 1973 were studied with emphasis on the kinds of the causative organisms and the susceptibility of these organisms to antibiotics. The findings in this study have served to help select antibiotics most likely to be effective against this disease. The overall incidence of purulent meningitis was 0.68%. This figure decreased little throughout the period. As for the frequency of causative organisms, Neisseria meningitidis led the list, and Diplococcus pneumoniae ranked just behind. Haemophilus influenzae was rare. The frequency of N. meningitidis, however, decreased sharply in spite of the essentially unchanged overall incidence of this disease. The probable reason for the poor prognosis of this disease in spite of the remarkable strides in chemotherapy is the decreased frequency of N. meningitidis and the inversely increased organisms that are resistant to usual chemotherapy. The therapeutic effectiveness of cefazolin against this disease was studied in 15 children including eight newborns and four infants. The daily per kg bodyweight dose was 50 mg or less in four, 50 approximately 100 mg in five, and more than 100 mg in the remaining six. The route of administration was either intramuscular or intravenous. No deaths occurred. The rate of effectiveness was as high as 80%. Residual symptoms were recorded in six and, in as many as five of them, the cause was a-tributable to the delayed detection of the disease. Neither side effects nor aberrent laboratory findings attributable to large doses of cefazolin were recorded. Diffusibility of cefazolin into the CSF was studied in nine subjects. The CSF concentration of this antibiotic was shown to be somewhat lower than that of ampicillin or cephaloridine and to account on an average for 13% of the mean peak serum level. This relatively low diffusibility will be offset by its high serum concentration and safe large-dose therapy. These findings have clearly shown that the therapeutic effectiveness of cefazolin is as high as that of ampicillin, and that this excellent effectiveness holds true even when the causative organism happens to be Escherichia coli, Klebsiella, etc. that are resistant to ampicillin. The authors have furthermore scrutinized much literature on the frequency of the causative organisms, emergence of resistant strains, and the diffusibility of antibiotics into the CSF, and arrived at the conclusion that cefazolin is a promising antibiotic of choice for the treatment of purulent meningitis in newborn. The daily dose is preferably 150 mg/kg or more given in three divided intravenous doses. Meanwhile ampicillin proved to be useful as the antibiotic of choice for the treatment of purulent meningitis in infants and children."}
{"id": "PMID:240049", "title": "A study on the rehabilitation of ischemic heart disease patients. The heart rate, beta-receptor blocking agents and strength-duration relationship of exercise.", "content": "Exercise tests with bicycle ergometer were performed in 9 normals and 54 patients with ischemic heart disease (IHD), in order to evaluate the heart rate (HR) as a parameter for determining the physical working capacity and controlling the daily activities, and to observe the circulatory and metabolic effects of beta-blockers and moreover to study the strength-duration relationship of exertion. The following results were obtained and discussed: 1. Reliable correlation between heart rate and O2 consumption during all phases of exercise, including the recovery period (R = 0.60-0.87, p less than 0.001) and parallelism of heart rate and pressure rate product allows the heart rate to be used as a parameter for myocardial O2 demand and ST-T changes. It is reasonable to evaluate the exercise effect by the net increment of heart rate during and after exercise, and to utilize the increment of heart rate in the recovery period for the evaluation of physical fitness and adaptability. 2. Similar to other studies made on beta-blockers, in this study too, the agents including K\u00f6 1366 suppressed the exercise responses of heart rate (p less than 0.01), the product of heart rate and blood pressure (p less than 0.01), and O2 consumption (p less than 0.01). But a relatively slow recovery of O2 consumption from the peak response towards pre-exercise level and a higher O2 pulse in the early recovery period was observed after beta-blocker medication. 3. Capillary (ear lobe) pH decreased and recovered in correlation with the strength of exertion. This corresponded with the response of other factors such as ST-T, heart rate, pressure-rate product, and O2 consumption, showing that the exercise strength was one of the more dominant factors to determine allowable work load for ischemic heart disease patients. 4. Recovery of pH was delayed after medication with K\u00f6 1366 (p less than 0.01).", "contents": "A study on the rehabilitation of ischemic heart disease patients. The heart rate, beta-receptor blocking agents and strength-duration relationship of exercise. Exercise tests with bicycle ergometer were performed in 9 normals and 54 patients with ischemic heart disease (IHD), in order to evaluate the heart rate (HR) as a parameter for determining the physical working capacity and controlling the daily activities, and to observe the circulatory and metabolic effects of beta-blockers and moreover to study the strength-duration relationship of exertion. The following results were obtained and discussed: 1. Reliable correlation between heart rate and O2 consumption during all phases of exercise, including the recovery period (R = 0.60-0.87, p less than 0.001) and parallelism of heart rate and pressure rate product allows the heart rate to be used as a parameter for myocardial O2 demand and ST-T changes. It is reasonable to evaluate the exercise effect by the net increment of heart rate during and after exercise, and to utilize the increment of heart rate in the recovery period for the evaluation of physical fitness and adaptability. 2. Similar to other studies made on beta-blockers, in this study too, the agents including K\u00f6 1366 suppressed the exercise responses of heart rate (p less than 0.01), the product of heart rate and blood pressure (p less than 0.01), and O2 consumption (p less than 0.01). But a relatively slow recovery of O2 consumption from the peak response towards pre-exercise level and a higher O2 pulse in the early recovery period was observed after beta-blocker medication. 3. Capillary (ear lobe) pH decreased and recovered in correlation with the strength of exertion. This corresponded with the response of other factors such as ST-T, heart rate, pressure-rate product, and O2 consumption, showing that the exercise strength was one of the more dominant factors to determine allowable work load for ischemic heart disease patients. 4. Recovery of pH was delayed after medication with K\u00f6 1366 (p less than 0.01)."}
{"id": "PMID:240050", "title": "Effects of beta blockers on cardiac function and myocardial oxygen consumption in the isolated supported heart preparation of the dog.", "content": "Effects of 2 different types of beta blockers, CS-359 and practolol, on mechanical performance and myocardial oxygen consumption (MVO2) in the isovolumic contraction of the isolated, blood-perfused canine heart with a support dog were studied. Two dose levels of the beta blockers were given intravenously to the support dog, one of which was enough to produce a significant beta adrenergic blocking action and other of which was a higher dose to reveal a direct depressant action on the isolated heart. CS-359 in the lower dose produced significant decreases in heart rate (HR), peak ventricular systolic pressure (peak VSP), and peak dp/dt while practolol caused no change in these parameters. The HR of the support dog was significantly decreased to the same degree in the lower dose of respective blocker. In the higher dose CS-359 decreased all parameters more definitely whereas practolol diminished peak VSP and peak dp/dt but did not significantly HR. MVO2 was decreased dose-relatedly by CS-359, but not affected significantly by practolol. From the analysis of relationships of MVO2 to peak VSP and HR in the isolated heart it is concluded that the effective reduction in MVO2 by CS-359 resulted mainly from a reduction in the peak VSP in the lower dose and additional decrease in HR in the higher dose of CS-359.", "contents": "Effects of beta blockers on cardiac function and myocardial oxygen consumption in the isolated supported heart preparation of the dog. Effects of 2 different types of beta blockers, CS-359 and practolol, on mechanical performance and myocardial oxygen consumption (MVO2) in the isovolumic contraction of the isolated, blood-perfused canine heart with a support dog were studied. Two dose levels of the beta blockers were given intravenously to the support dog, one of which was enough to produce a significant beta adrenergic blocking action and other of which was a higher dose to reveal a direct depressant action on the isolated heart. CS-359 in the lower dose produced significant decreases in heart rate (HR), peak ventricular systolic pressure (peak VSP), and peak dp/dt while practolol caused no change in these parameters. The HR of the support dog was significantly decreased to the same degree in the lower dose of respective blocker. In the higher dose CS-359 decreased all parameters more definitely whereas practolol diminished peak VSP and peak dp/dt but did not significantly HR. MVO2 was decreased dose-relatedly by CS-359, but not affected significantly by practolol. From the analysis of relationships of MVO2 to peak VSP and HR in the isolated heart it is concluded that the effective reduction in MVO2 by CS-359 resulted mainly from a reduction in the peak VSP in the lower dose and additional decrease in HR in the higher dose of CS-359."}
{"id": "PMID:240054", "title": "Effect of starvation on renal metabolism in the rat.", "content": "The effects of starvation on the acid-base status of the rat and on the glucoeogenic and ammoniagenic capacity of rat renal-cortical slices were examined.  Starvation for 48 or 72 hr did not affect acid-base status, and urinary ammonia production did not change.  Kidney cortical slices from starved as compared to fed rats showed increased gluconeogenic capacity when incubated with the substrated pyruvate, succinate, fumarate, malate, 2-oxyoglutarate, glutamine and glutamate.  Renal cortical tissue from starved rats also had increased activity of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase.  Renal cortical slices from starved rats did not differ from those from fed rats in the ability to produce ammonia from glutamine or glutamate, nor was there any difference inhe activity of glutaminase between these groups.  These results show that renal gluconeogenic capacity is increased in starved rats in the absence of systemic acidosis, and starvation does not lead to an increase in urinary ammonia excretion or renal ammoniagenic capacity.", "contents": "Effect of starvation on renal metabolism in the rat. The effects of starvation on the acid-base status of the rat and on the glucoeogenic and ammoniagenic capacity of rat renal-cortical slices were examined.  Starvation for 48 or 72 hr did not affect acid-base status, and urinary ammonia production did not change.  Kidney cortical slices from starved as compared to fed rats showed increased gluconeogenic capacity when incubated with the substrated pyruvate, succinate, fumarate, malate, 2-oxyoglutarate, glutamine and glutamate.  Renal cortical tissue from starved rats also had increased activity of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase.  Renal cortical slices from starved rats did not differ from those from fed rats in the ability to produce ammonia from glutamine or glutamate, nor was there any difference inhe activity of glutaminase between these groups.  These results show that renal gluconeogenic capacity is increased in starved rats in the absence of systemic acidosis, and starvation does not lead to an increase in urinary ammonia excretion or renal ammoniagenic capacity."}
{"id": "PMID:240055", "title": "Effects of nephron reduction and dietary protein content on renal ammoniagenesis in the rat.", "content": "Urinary ammonium excretion, in vitro ammoniagenesis and the activities of renal cortical phosphate-dependent glutaminase (PDG) and glutamic dehydrogenase (GLDH) were measured in rats with a reduced renal mass. Following contralateral nephrectomy, ammonium excretion per nephron, ammonia production and the activities of PDG and GLDH were all increased significantly in remnant kidneys of rats fed high protein diets. In rats fed low protein diets, although PDG activity increased, GLDH activity and ammonia production and excretion did not increase in remnant kidneys following contralateral nephrectomy. Ammonia production and excretion were greater in rats fed high than low protein diets, a difference that was corrected by the addition of mineral acid to the diets of low protein-fed rats. Acid supplementation to the low protein group did not result in enhanced ammonia production or GLDH activity following a reduction in renal mass. The data indicate that the increased rate of ammoniagenesis which occurs following nephron reduction is markedly influenced by dietary protein content. A lack of enhanced GLDH activity may underlie the lack of increased ammonia production of low protein-fed rats following nephron reduction.", "contents": "Effects of nephron reduction and dietary protein content on renal ammoniagenesis in the rat. Urinary ammonium excretion, in vitro ammoniagenesis and the activities of renal cortical phosphate-dependent glutaminase (PDG) and glutamic dehydrogenase (GLDH) were measured in rats with a reduced renal mass. Following contralateral nephrectomy, ammonium excretion per nephron, ammonia production and the activities of PDG and GLDH were all increased significantly in remnant kidneys of rats fed high protein diets. In rats fed low protein diets, although PDG activity increased, GLDH activity and ammonia production and excretion did not increase in remnant kidneys following contralateral nephrectomy. Ammonia production and excretion were greater in rats fed high than low protein diets, a difference that was corrected by the addition of mineral acid to the diets of low protein-fed rats. Acid supplementation to the low protein group did not result in enhanced ammonia production or GLDH activity following a reduction in renal mass. The data indicate that the increased rate of ammoniagenesis which occurs following nephron reduction is markedly influenced by dietary protein content. A lack of enhanced GLDH activity may underlie the lack of increased ammonia production of low protein-fed rats following nephron reduction."}
{"id": "PMID:240057", "title": "Renal secretion of diphosphonates in rats.", "content": "Diphosphonates, characterized by a P--C--P bond, are relatively new experimental drugs used for the treatment of myositis ossificans, dental calculus, nephrolithiasis and Paget's disease. These compounds are not metabolized and the fraction which is not taken up by the skeleton is excreted unchanged in the urine. In the present study, the renal clearances of two 14C-labelled diphosphonates, disodium ethane-1-hydroxy-1,1-diphosphonate (CEHDP) and disodium dichloromethylene diphosphonate (CC12MDP) have been measured in conscious rats. The clearances have been found to be higher than the glomerular filtration rate (GFR), Cdiphosphonate/GFR being about 1.5. This observation indicates net tubular secretion of both drugs. High plasma concentration of EHDP or Cl2MDP significantly depressed CEHDP, whereas CEHDP was not influenced by varying urine pH, by infusing NH4Cl or NaHCO3, or by simultaneous administration of high doses of para-aminohippurate (PAH), probenecid, N-methylnicotinamide or Ca-EDTA. High plasma concentration of inorganic phosphate depressed CEHDP and also depressed the in vitro ultrafiltrability of EHDP. In conclusion, these results provide evidence of an active renal transport of diphosphonates which appears distinct from the mechanisms handling organic acids, organic bases and EDTA in the rat kidney.", "contents": "Renal secretion of diphosphonates in rats. Diphosphonates, characterized by a P--C--P bond, are relatively new experimental drugs used for the treatment of myositis ossificans, dental calculus, nephrolithiasis and Paget's disease. These compounds are not metabolized and the fraction which is not taken up by the skeleton is excreted unchanged in the urine. In the present study, the renal clearances of two 14C-labelled diphosphonates, disodium ethane-1-hydroxy-1,1-diphosphonate (CEHDP) and disodium dichloromethylene diphosphonate (CC12MDP) have been measured in conscious rats. The clearances have been found to be higher than the glomerular filtration rate (GFR), Cdiphosphonate/GFR being about 1.5. This observation indicates net tubular secretion of both drugs. High plasma concentration of EHDP or Cl2MDP significantly depressed CEHDP, whereas CEHDP was not influenced by varying urine pH, by infusing NH4Cl or NaHCO3, or by simultaneous administration of high doses of para-aminohippurate (PAH), probenecid, N-methylnicotinamide or Ca-EDTA. High plasma concentration of inorganic phosphate depressed CEHDP and also depressed the in vitro ultrafiltrability of EHDP. In conclusion, these results provide evidence of an active renal transport of diphosphonates which appears distinct from the mechanisms handling organic acids, organic bases and EDTA in the rat kidney."}
{"id": "PMID:240063", "title": "[New views on the significance and treatment of undescended testis (author's transl)].", "content": "Undescended testis is of clinical importance because there are increased risks of milignancy and torsion and disturbances of fertility and psychosexual development. New quantitative morphologic investigations show that human prepubertal testicular maturation does not occur in phases but is continuous. This made it necessary to investigate afresh the causes of disturbance of fertility and the treatment of indescended testis. Our own investigations show that damage to the germ epithelium need not be congenital but may develop because of its ectopy. If, in dogs, a testis is placed into the abdomen, not only this but also the normally placed testis in the scrotum is damaged. The diameter of the tubules and their surfaces as well as the numbers of pachtenous primary spermatocytes are significantly reduced both in the displaced and the normally placed testis. Nuclear surfaces and density of the cells involved in spermatogenesis differ from those in the controls. The findings support the plea for early hormonal or surgical treatment in order to prevent later disturbances of fertility.", "contents": "[New views on the significance and treatment of undescended testis (author's transl)]. Undescended testis is of clinical importance because there are increased risks of milignancy and torsion and disturbances of fertility and psychosexual development. New quantitative morphologic investigations show that human prepubertal testicular maturation does not occur in phases but is continuous. This made it necessary to investigate afresh the causes of disturbance of fertility and the treatment of indescended testis. Our own investigations show that damage to the germ epithelium need not be congenital but may develop because of its ectopy. If, in dogs, a testis is placed into the abdomen, not only this but also the normally placed testis in the scrotum is damaged. The diameter of the tubules and their surfaces as well as the numbers of pachtenous primary spermatocytes are significantly reduced both in the displaced and the normally placed testis. Nuclear surfaces and density of the cells involved in spermatogenesis differ from those in the controls. The findings support the plea for early hormonal or surgical treatment in order to prevent later disturbances of fertility."}
{"id": "PMID:240064", "title": "Neuroleptanalgesic drug combinations in the anaesthetic management of small laboratory animals.", "content": "Trials of different drug combinations for use in rabbits, guinea-pigs, rats, hamsters and mice are described in detail and experience over a 5-year period evaluated. Combinations of fentanyl citrate, fluanisone and diazepam provided exceptionally good anaesthesia in each species and were considered superior to other injectable agents.", "contents": "Neuroleptanalgesic drug combinations in the anaesthetic management of small laboratory animals. Trials of different drug combinations for use in rabbits, guinea-pigs, rats, hamsters and mice are described in detail and experience over a 5-year period evaluated. Combinations of fentanyl citrate, fluanisone and diazepam provided exceptionally good anaesthesia in each species and were considered superior to other injectable agents."}
{"id": "PMID:240065", "title": "Women alcoholics. A review of social and psychological studies.", "content": "Research on social-history variables, personality characteristics, social roles and role confusion, and possible treatment methods for women alcoholics is reviewed. Suggestions for additional studies involving factors motivating drinking in women, theories of personality, new treatment methods, and differentiation between subgroups of women alcoholics are discussed.", "contents": "Women alcoholics. A review of social and psychological studies. Research on social-history variables, personality characteristics, social roles and role confusion, and possible treatment methods for women alcoholics is reviewed. Suggestions for additional studies involving factors motivating drinking in women, theories of personality, new treatment methods, and differentiation between subgroups of women alcoholics are discussed."}
{"id": "PMID:240066", "title": "Dimensions of psychopathology among alcoholic patients.", "content": "Responses of hospitalized alcoholics to the Minnesota Multiphasic Personality Inventory and the Differential Personality Inventory were intercorrelated and factor analyzed. Considerable heterogeneity of psychopathology within the sample was found.", "contents": "Dimensions of psychopathology among alcoholic patients. Responses of hospitalized alcoholics to the Minnesota Multiphasic Personality Inventory and the Differential Personality Inventory were intercorrelated and factor analyzed. Considerable heterogeneity of psychopathology within the sample was found."}
{"id": "PMID:240067", "title": "Psychological test results at three stages of inpatient alcoholism treatment.", "content": "Improvement in intellectual, perceptual-motor and personality functioning was observed in men alcoholics after 30 and 60 days of treatment. On the basis of results with the Minnesota Multiphasic Personality Inventory, four consistent personality clusters were identified.", "contents": "Psychological test results at three stages of inpatient alcoholism treatment. Improvement in intellectual, perceptual-motor and personality functioning was observed in men alcoholics after 30 and 60 days of treatment. On the basis of results with the Minnesota Multiphasic Personality Inventory, four consistent personality clusters were identified."}
{"id": "PMID:240068", "title": "Alcoholism and schizophrenia: the search for perspectives. A review.", "content": "The historical search for meaningful relationships between alcoholism and schizophrenia is reviewed. The results are considered inconclusive and further lines of research are suggested.", "contents": "Alcoholism and schizophrenia: the search for perspectives. A review. The historical search for meaningful relationships between alcoholism and schizophrenia is reviewed. The results are considered inconclusive and further lines of research are suggested."}
{"id": "PMID:240069", "title": "Relationships between specific drinking problems in early adulthood and middle age. An exploratory 20-year follow-up study.", "content": "Specific drinking problems were remeasured in a panel study after a 20-year interval. The nature of the problems at both measurement points is assessed and the associations between them explored.", "contents": "Relationships between specific drinking problems in early adulthood and middle age. An exploratory 20-year follow-up study. Specific drinking problems were remeasured in a panel study after a 20-year interval. The nature of the problems at both measurement points is assessed and the associations between them explored."}
{"id": "PMID:240070", "title": "Drinking behavior and \"alcoholism\".", "content": "Drinking is viewed as a functional behavior, an active response to environmental conditions, and excessive drinking as a compromise behavior resulting from ineffectiveness in mediating goals and resolving problems.", "contents": "Drinking behavior and \"alcoholism\". Drinking is viewed as a functional behavior, an active response to environmental conditions, and excessive drinking as a compromise behavior resulting from ineffectiveness in mediating goals and resolving problems."}
{"id": "PMID:240071", "title": "Alcohol consumption and personal resources. A general hypothesis and some implications.", "content": "A general hypothesis is formulated in which alcohol consumption is largely determined by the resources available for drinking, the activities competing for those resources, and the costs associated with drinking in the context of a particular social status. Implications in terms of drinking patterns of occupational subgroups, longitudinal changes in alcohol consumption, and vulnerability to the development of pathological drinking are suggested.", "contents": "Alcohol consumption and personal resources. A general hypothesis and some implications. A general hypothesis is formulated in which alcohol consumption is largely determined by the resources available for drinking, the activities competing for those resources, and the costs associated with drinking in the context of a particular social status. Implications in terms of drinking patterns of occupational subgroups, longitudinal changes in alcohol consumption, and vulnerability to the development of pathological drinking are suggested."}
{"id": "PMID:240072", "title": "Mixed models of alcoholism. Definitions, etiology, treatment and prognosis in health education textbooks.", "content": "The information on alcoholism presented in college-level health education textbooks was compared with eight models of alcoholism. No model was cited consistently; diverse knowledge bases, models of alcoholism and moral views were implicit in the texts. The utility of the models is also discussed.", "contents": "Mixed models of alcoholism. Definitions, etiology, treatment and prognosis in health education textbooks. The information on alcoholism presented in college-level health education textbooks was compared with eight models of alcoholism. No model was cited consistently; diverse knowledge bases, models of alcoholism and moral views were implicit in the texts. The utility of the models is also discussed."}
{"id": "PMID:240073", "title": "Training paraprofessionals in the treatment of alcoholism. Effects on knowledge, attitudes and therapeutic techniques.", "content": "Participation in a training program for paraprofessional alcoholism counselors increased the trainees' knowledge of alcoholism, modified their attitudes toward alcoholism and affected their therapeutic techniques.", "contents": "Training paraprofessionals in the treatment of alcoholism. Effects on knowledge, attitudes and therapeutic techniques. Participation in a training program for paraprofessional alcoholism counselors increased the trainees' knowledge of alcoholism, modified their attitudes toward alcoholism and affected their therapeutic techniques."}
{"id": "PMID:240074", "title": "Physicians and alcoholics. The effect of medical training on attitudes toward alcoholics.", "content": "The over-all ratings assigned by first- and second-year medical students and housestaff (residents and interns) to alcoholics on a 16-adjectivee bipolar semantic differential measure differed significantly. Mean ratings by the housestaff were lowest and the ratings by the second-year students were lower than those of the first-year students on 5 of the 6 adjective pairs on which the groups differed significantly.", "contents": "Physicians and alcoholics. The effect of medical training on attitudes toward alcoholics. The over-all ratings assigned by first- and second-year medical students and housestaff (residents and interns) to alcoholics on a 16-adjectivee bipolar semantic differential measure differed significantly. Mean ratings by the housestaff were lowest and the ratings by the second-year students were lower than those of the first-year students on 5 of the 6 adjective pairs on which the groups differed significantly."}
{"id": "PMID:240075", "title": "Drinking-driving behavior of young men in relation to accidents.", "content": "To determine the role of drinking in the accidents of young men, data were examined from a representative survey sample of 1670 young men in south-eastern Michigan and from official accident statistics of 4 states. By age 20 over half the sampled men drank at least once weekly and drove at least once monthly after drinking. Alcohol was involved in 3-8% of all crashes of 20-year-olds. The highest accident rates without alcohol involvement occurred at ages 18-20, whereas the most alcohol-involved accidents occured at ages 22-24.", "contents": "Drinking-driving behavior of young men in relation to accidents. To determine the role of drinking in the accidents of young men, data were examined from a representative survey sample of 1670 young men in south-eastern Michigan and from official accident statistics of 4 states. By age 20 over half the sampled men drank at least once weekly and drove at least once monthly after drinking. Alcohol was involved in 3-8% of all crashes of 20-year-olds. The highest accident rates without alcohol involvement occurred at ages 18-20, whereas the most alcohol-involved accidents occured at ages 22-24."}
{"id": "PMID:240076", "title": "Cross-fostering of DBA and C57Bl mice. Increase in voluntary consumption of alcohol by DBA weanlings.", "content": "Weanling mice of the alcohol-avoiding DBA strain cross-fostered to mothers of the alcohol-selecting C57Bl strain drank twice as much alcohol as did nonfostered DBA mice. In contrast, C57Bl mice cross-fostered to DBA mothers drank the same amount of alcohol as did nonfostered C57Bl mice. Differences in maternal behavior seem to be responsible for differences in alcohol selection by weanlings.", "contents": "Cross-fostering of DBA and C57Bl mice. Increase in voluntary consumption of alcohol by DBA weanlings. Weanling mice of the alcohol-avoiding DBA strain cross-fostered to mothers of the alcohol-selecting C57Bl strain drank twice as much alcohol as did nonfostered DBA mice. In contrast, C57Bl mice cross-fostered to DBA mothers drank the same amount of alcohol as did nonfostered C57Bl mice. Differences in maternal behavior seem to be responsible for differences in alcohol selection by weanlings."}
{"id": "PMID:240077", "title": "Drinking patterns of institutionalized and noninstitutionalized Wyoming youth.", "content": "The drinking attitudes and patterns among institutionalized and noninstitutionalized Wyoming youth were examined. The majority appeared generally to support a norm of approval of drinking but those institutionalized for antisocial behavior were more likely to drink often, to become drunk and to have gotten into trouble with parents or the police because of drinking.", "contents": "Drinking patterns of institutionalized and noninstitutionalized Wyoming youth. The drinking attitudes and patterns among institutionalized and noninstitutionalized Wyoming youth were examined. The majority appeared generally to support a norm of approval of drinking but those institutionalized for antisocial behavior were more likely to drink often, to become drunk and to have gotten into trouble with parents or the police because of drinking."}
{"id": "PMID:240078", "title": "An intake group in the alcoholism outpatient clinic.", "content": "At an outpatient clinic, alcoholics who attended group meetings dealing with basic communication skills during the admission process missed fewer appointments and more often completed the process than did alcoholics who did not attend the meetings.", "contents": "An intake group in the alcoholism outpatient clinic. At an outpatient clinic, alcoholics who attended group meetings dealing with basic communication skills during the admission process missed fewer appointments and more often completed the process than did alcoholics who did not attend the meetings."}
{"id": "PMID:240079", "title": "Transplantation models using the regional lymph node.", "content": "Several transplantation models, using the regional lymph node, to study the transplantation reaction in strictly defined and simple conditions were devised. Lymphoid cells were transplanted to inbred rats and mice at the sites drained by one regional lymph node; the experimental design was chosen so as to permit theoretically a one-way reaction, either the host-versus-graft (HVG) or the graft-versus-host (GVH) reaction. The changes in the lymph nodes draining the site of cell injection (weight increase, histology, lymphocyte activation) were very similar in both transplantation reactions. They were ascribed to a humoral mediator released upon the contact of lymphoid cells from two genetically different individuals. The direct demonstration of a mediator which is capable of activating the regional lymph node in vivo introduces some new aspects into the process of sensitization after transplantation.", "contents": "Transplantation models using the regional lymph node. Several transplantation models, using the regional lymph node, to study the transplantation reaction in strictly defined and simple conditions were devised. Lymphoid cells were transplanted to inbred rats and mice at the sites drained by one regional lymph node; the experimental design was chosen so as to permit theoretically a one-way reaction, either the host-versus-graft (HVG) or the graft-versus-host (GVH) reaction. The changes in the lymph nodes draining the site of cell injection (weight increase, histology, lymphocyte activation) were very similar in both transplantation reactions. They were ascribed to a humoral mediator released upon the contact of lymphoid cells from two genetically different individuals. The direct demonstration of a mediator which is capable of activating the regional lymph node in vivo introduces some new aspects into the process of sensitization after transplantation."}
{"id": "PMID:240080", "title": "[Restoration of articular movement after injury using the Volkov-Oganesian appliance].", "content": "Volkov-Oganiesian's apparatus takes over the whole statical and dynamical load and releases the articulation completely. The apparatus fills the gap created between the articular surfaces both in statical and dynamical respect, it eliminates the friction and overcomes also the effect of the reflex muscular contracture. In the same time it eliminates also the superfluous muscular movements, since the apparatus is fixed firmly to the bone, and the exact centring of the articular ends (being of extreme importance in the surgical treatment of the luxation and subluxation) promotes the formation of the newly developed articular surfaces.", "contents": "[Restoration of articular movement after injury using the Volkov-Oganesian appliance]. Volkov-Oganiesian's apparatus takes over the whole statical and dynamical load and releases the articulation completely. The apparatus fills the gap created between the articular surfaces both in statical and dynamical respect, it eliminates the friction and overcomes also the effect of the reflex muscular contracture. In the same time it eliminates also the superfluous muscular movements, since the apparatus is fixed firmly to the bone, and the exact centring of the articular ends (being of extreme importance in the surgical treatment of the luxation and subluxation) promotes the formation of the newly developed articular surfaces."}
{"id": "PMID:240081", "title": "[Infection in bone surgery].", "content": "After surgical interventions carried out in the bone different occurrence of infections in various institutes has been observed, - the infections are in general more infrequent in the specialized institutes and departments. In the authors' opinion, - besides the general asepsis the special conditions of work and the working tools play important role in the prevention of infections. In the indication of surgical intervention in the bone the surgeon must have self-criticism, - this may lead to the reduction of infections. Several data have shown that all interventions are not allowed everywhere and always.", "contents": "[Infection in bone surgery]. After surgical interventions carried out in the bone different occurrence of infections in various institutes has been observed, - the infections are in general more infrequent in the specialized institutes and departments. In the authors' opinion, - besides the general asepsis the special conditions of work and the working tools play important role in the prevention of infections. In the indication of surgical intervention in the bone the surgeon must have self-criticism, - this may lead to the reduction of infections. Several data have shown that all interventions are not allowed everywhere and always."}
{"id": "PMID:240082", "title": "[Primary excision of burn wounds].", "content": "After the clarification of the pathophysiology of the shock suffered in burns and after working out the successful shock therapy -, as well as after the surgical removal of the necrosed tissues and the introduction of the up-to-date dermoplasty the prognosis of the thermic trauma has undergone fundamental change. The tangential and laminal excision - that is the removal of the necrosed areas with dermatological knife - has been introduced in 1968. Ater the review of the secondary surgical interventions the new method, its advantages and limits, as well as their experiences are discussed by the authors. This method has elevated the primary care of the burns to the level of the therapy of the mechanical wounds and it has allowed the application of Friedrich's principle also in the surgical treatment of the thermic trauma. The proportion of the contractures decreased considerably, - and this may be considered as a great progress, even in the case that the mortality of the severe burns could not be reduced in greater degree. The institution and the use of the tangential excision is already of beneficial effect.", "contents": "[Primary excision of burn wounds]. After the clarification of the pathophysiology of the shock suffered in burns and after working out the successful shock therapy -, as well as after the surgical removal of the necrosed tissues and the introduction of the up-to-date dermoplasty the prognosis of the thermic trauma has undergone fundamental change. The tangential and laminal excision - that is the removal of the necrosed areas with dermatological knife - has been introduced in 1968. Ater the review of the secondary surgical interventions the new method, its advantages and limits, as well as their experiences are discussed by the authors. This method has elevated the primary care of the burns to the level of the therapy of the mechanical wounds and it has allowed the application of Friedrich's principle also in the surgical treatment of the thermic trauma. The proportion of the contractures decreased considerably, - and this may be considered as a great progress, even in the case that the mortality of the severe burns could not be reduced in greater degree. The institution and the use of the tangential excision is already of beneficial effect."}
{"id": "PMID:240083", "title": "[Results of panastragal arthrodesis performed on basis of different indications].", "content": "The indications of pantalar arthrodeses - performed in 21 years - and their results are discussed. In the authors' opinion, the compression arthrodessis carried out in one sitting is the method of choice.", "contents": "[Results of panastragal arthrodesis performed on basis of different indications]. The indications of pantalar arthrodeses - performed in 21 years - and their results are discussed. In the authors' opinion, the compression arthrodessis carried out in one sitting is the method of choice."}
{"id": "PMID:240084", "title": "[Possibilities of treatment of arthrogryposis].", "content": "The results of the treatment of 90 patients with arthrogryposis are resumed. The possibilities of the conservative treatment are discussed and on the basis of their experiences and the data of the literature the details of the surgical technique are given for each articulation. Besides conservative therapy 86 different surgical interventions have been performed on 21 patients. The treatment necessitates utmost care and good collaboration is necessary between the doctor and the patient, or the patients relatives, resp. The therapeutical program yields often after several years satisfactory result.", "contents": "[Possibilities of treatment of arthrogryposis]. The results of the treatment of 90 patients with arthrogryposis are resumed. The possibilities of the conservative treatment are discussed and on the basis of their experiences and the data of the literature the details of the surgical technique are given for each articulation. Besides conservative therapy 86 different surgical interventions have been performed on 21 patients. The treatment necessitates utmost care and good collaboration is necessary between the doctor and the patient, or the patients relatives, resp. The therapeutical program yields often after several years satisfactory result."}
{"id": "PMID:240085", "title": "[Fenestrated rib fracture, a disease entity?].", "content": "The problems of the paradoxical respiration - observed in the case of fenestrated rib fracture - are discussed by the authors. On the basis of the data of the literature and of 348 own cases with covered rib fracture, as well as on the basis of the course and the clinical analysis of the lesion the authors refuse to admit the role of the \"pendelluft\" and of the mediastinal flutter in the development of circulatory and respiratory disorders occurring in the case of fenestrated rib fractures. In the authors' opinion, there are only quantitative differences between the consequences of the various rib fractures. The thoracal lesion is considered by the authors as functional unity. The treatment is always prescribed according to the degree of the functional disorder and also the classification of the injured patients is to be made on this basis.", "contents": "[Fenestrated rib fracture, a disease entity?]. The problems of the paradoxical respiration - observed in the case of fenestrated rib fracture - are discussed by the authors. On the basis of the data of the literature and of 348 own cases with covered rib fracture, as well as on the basis of the course and the clinical analysis of the lesion the authors refuse to admit the role of the \"pendelluft\" and of the mediastinal flutter in the development of circulatory and respiratory disorders occurring in the case of fenestrated rib fractures. In the authors' opinion, there are only quantitative differences between the consequences of the various rib fractures. The thoracal lesion is considered by the authors as functional unity. The treatment is always prescribed according to the degree of the functional disorder and also the classification of the injured patients is to be made on this basis."}
{"id": "PMID:240086", "title": "[Positive contrast arthrography in the diagnosis of ligament lesions in the upper ankle joint].", "content": "There are a great number of open questions in the diagnosis and the management of ligament lesions of the ankle joint. On the basis of the data of the literature and the author's experiences the advantages of the contrast arthrography of the ankle-joint may be resumed in the following: 1. No narcosis is necessary. 2. More exact determination of the site of the lesion is possible. 3. Therefore proper treatment may be chosen. 4. The incidental technical errors are more easily to be verified. (Paraarticular administration of the contrast medium is immediately demonstrable, whereas faulty observance of the prescriprions becomes not always evident from the roentgenogram). 5. No comparative roentgenograms are necessary. 6. The X-ray staff is not exposed to X-ray radiation.", "contents": "[Positive contrast arthrography in the diagnosis of ligament lesions in the upper ankle joint]. There are a great number of open questions in the diagnosis and the management of ligament lesions of the ankle joint. On the basis of the data of the literature and the author's experiences the advantages of the contrast arthrography of the ankle-joint may be resumed in the following: 1. No narcosis is necessary. 2. More exact determination of the site of the lesion is possible. 3. Therefore proper treatment may be chosen. 4. The incidental technical errors are more easily to be verified. (Paraarticular administration of the contrast medium is immediately demonstrable, whereas faulty observance of the prescriprions becomes not always evident from the roentgenogram). 5. No comparative roentgenograms are necessary. 6. The X-ray staff is not exposed to X-ray radiation."}
{"id": "PMID:240087", "title": "[Supplying patients with orthopedic shoes after panastragal arthrodesis].", "content": "After the arthrodesis of the upper and lower articulations and of the Chopart's articulations (panastragal arthrodesis) the foot's functions undergoes a change, which may be substituted only with properly constructed orthopaedic shoes. Partly the foot's function - altered in consequence of the intervention - and partly the considerations to be respected at the preparation of the orthopaedic shoes are discussed in the paper.", "contents": "[Supplying patients with orthopedic shoes after panastragal arthrodesis]. After the arthrodesis of the upper and lower articulations and of the Chopart's articulations (panastragal arthrodesis) the foot's functions undergoes a change, which may be substituted only with properly constructed orthopaedic shoes. Partly the foot's function - altered in consequence of the intervention - and partly the considerations to be respected at the preparation of the orthopaedic shoes are discussed in the paper."}
{"id": "PMID:240088", "title": "[Experience with artificial hibernation of patients with severe craniocerebral injuries].", "content": "The artificial hibernation (hypothermia) of patients with severe cranio-cerebral lesion is discussed. The authors' experiences have shown that re-establishment of the normothermia reduces considerably the symptoms of the neurovegetative syndrome, thus it contributes to the improvement of the prognosis and in many cases it assures the patient's survival. Artificial hibernation is an important task during the intensive therapy of patients with cranio-cerebral lesions.", "contents": "[Experience with artificial hibernation of patients with severe craniocerebral injuries]. The artificial hibernation (hypothermia) of patients with severe cranio-cerebral lesion is discussed. The authors' experiences have shown that re-establishment of the normothermia reduces considerably the symptoms of the neurovegetative syndrome, thus it contributes to the improvement of the prognosis and in many cases it assures the patient's survival. Artificial hibernation is an important task during the intensive therapy of patients with cranio-cerebral lesions."}
{"id": "PMID:240089", "title": "[Experience with the treatment of longitudinal oblique and spiral fractures of the leg by Goetze's percutaneous cerclage].", "content": "After the short review of the literary data in respect of Goetze's percutaneous cerclage 25 cases are presented: in all cases satisfactory functional results have been obtained. With proper use this method is useful for the treatment of long oblique and spiral fractures of the leg, if suitable technical equipment is available.", "contents": "[Experience with the treatment of longitudinal oblique and spiral fractures of the leg by Goetze's percutaneous cerclage]. After the short review of the literary data in respect of Goetze's percutaneous cerclage 25 cases are presented: in all cases satisfactory functional results have been obtained. With proper use this method is useful for the treatment of long oblique and spiral fractures of the leg, if suitable technical equipment is available."}
{"id": "PMID:240090", "title": "[Organization of the management of burns in mass disasters].", "content": "In war-time or in the case of other mass casualties we are compelled to have recourse to a compromise between the great number of the injured individuals and the possibilities of their management. This compromise, however, should not become distorted to an inevitable concession to our medical principles. The care of mass casualties - resulting also from burns - is an integrant area of up-to-date medicine, requiring full responsibility. It is our sublime obligation to study and to teach this discipline.", "contents": "[Organization of the management of burns in mass disasters]. In war-time or in the case of other mass casualties we are compelled to have recourse to a compromise between the great number of the injured individuals and the possibilities of their management. This compromise, however, should not become distorted to an inevitable concession to our medical principles. The care of mass casualties - resulting also from burns - is an integrant area of up-to-date medicine, requiring full responsibility. It is our sublime obligation to study and to teach this discipline."}
{"id": "PMID:240091", "title": "[Accidental immobilization of the proximal joint of the index finger].", "content": "In connexion with one case a rare clinical picture is described by the authors. The stoppage of movement observed in young individuals in the MP articulation of the forefinger occurs under the effect of trauma, - under normal articular conditions, - on strongly flexed finger, under the effect of powerful ulnar duction.", "contents": "[Accidental immobilization of the proximal joint of the index finger]. In connexion with one case a rare clinical picture is described by the authors. The stoppage of movement observed in young individuals in the MP articulation of the forefinger occurs under the effect of trauma, - under normal articular conditions, - on strongly flexed finger, under the effect of powerful ulnar duction."}
{"id": "PMID:240093", "title": "The heart and hyperthyroidism. Use of beta-adrenergic blocking drugs.", "content": "Many of the manifestations of hyperthyroidism are secondary to increased adrenergic activity. In recent years the beta adrenergic blocking drugs, as represented by d,1-propranolol, have become the agents of choice for ameliorating the adrenergic signs and symptoms of hyperthyroidism. Propranolol improves the tachycardia, tremor, restlessness, anxiety, and myopathy.", "contents": "The heart and hyperthyroidism. Use of beta-adrenergic blocking drugs. Many of the manifestations of hyperthyroidism are secondary to increased adrenergic activity. In recent years the beta adrenergic blocking drugs, as represented by d,1-propranolol, have become the agents of choice for ameliorating the adrenergic signs and symptoms of hyperthyroidism. Propranolol improves the tachycardia, tremor, restlessness, anxiety, and myopathy."}
{"id": "PMID:240102", "title": "Purification and characterization of a Streptomyces albus endo-N-acetylmuramidase lytic for group A and other beta haemolytic streptococci.", "content": "The purification and characterization of the streptolytic exo-enzyme from the Maxted-McCarty strain of Streptomyces albus is described. This enzyme was shown to be an endo-N-acetylmuramidase with a molecular weight of 10 to 12,000 and optimal activity at pH 8 and 45 degrees C. The enzyme is lytic for streptococci of various groups, Micrococcus lysodeikticus, Staphylococcus aureus, as well as Escherichia coli. It closely resembles the F1 endo-N-acetylmuramidase described by Ghuysen et al. (1966) except for small differences in the products of lysis of streptococcal cell walls and the resistance of Escherichia coli to lysis by the F1 enzyme. Lysates of group A and A variant streptococcal cell walls prepared with purified Streptomyces albus muramidase contained serologically active M protein and C carbohydrate-peptidoglycan complexes. The chemical and immunological characteristics of these enzymmatic products of streptococcal cell walls are reported and their utility as immunologic reagents is described.", "contents": "Purification and characterization of a Streptomyces albus endo-N-acetylmuramidase lytic for group A and other beta haemolytic streptococci. The purification and characterization of the streptolytic exo-enzyme from the Maxted-McCarty strain of Streptomyces albus is described. This enzyme was shown to be an endo-N-acetylmuramidase with a molecular weight of 10 to 12,000 and optimal activity at pH 8 and 45 degrees C. The enzyme is lytic for streptococci of various groups, Micrococcus lysodeikticus, Staphylococcus aureus, as well as Escherichia coli. It closely resembles the F1 endo-N-acetylmuramidase described by Ghuysen et al. (1966) except for small differences in the products of lysis of streptococcal cell walls and the resistance of Escherichia coli to lysis by the F1 enzyme. Lysates of group A and A variant streptococcal cell walls prepared with purified Streptomyces albus muramidase contained serologically active M protein and C carbohydrate-peptidoglycan complexes. The chemical and immunological characteristics of these enzymmatic products of streptococcal cell walls are reported and their utility as immunologic reagents is described."}
{"id": "PMID:240103", "title": "Cholesterol metabolism by Mycobacterium.", "content": "Cholesterol metabolism by Mycobacterium species ATCC Number 19652 was studied in defined media. Whole cells were found to take up 91% of the total cholesterol when incubated five days at 34 degrees C in media of pH 6.8-7.4. Uptake of cholesterol by whole cells could be significantly inhibited by 2,4-dinitrophenol and dicyclohexylcarbodiimide. Growth media supernates as well as isolated microbial cell walls were found to contain cholesterol hydrolysing activity. This activity was extractable by Triton X-100 and appeared to have a molecular weight of approximately 100-200,000.", "contents": "Cholesterol metabolism by Mycobacterium. Cholesterol metabolism by Mycobacterium species ATCC Number 19652 was studied in defined media. Whole cells were found to take up 91% of the total cholesterol when incubated five days at 34 degrees C in media of pH 6.8-7.4. Uptake of cholesterol by whole cells could be significantly inhibited by 2,4-dinitrophenol and dicyclohexylcarbodiimide. Growth media supernates as well as isolated microbial cell walls were found to contain cholesterol hydrolysing activity. This activity was extractable by Triton X-100 and appeared to have a molecular weight of approximately 100-200,000."}
{"id": "PMID:240104", "title": "[Change in the indices of direct count of bacteria in cultures and pond water at different pH].", "content": "Experiments were carried out with the pure cultures of Pseudomonas fluorescens and Bacillus subtilis, and with pond water. The adjustment of pH of the culture or water to 8.8--9.0 facilitates the direct count of the microorganisms, and makes the results more accurate.", "contents": "[Change in the indices of direct count of bacteria in cultures and pond water at different pH]. Experiments were carried out with the pure cultures of Pseudomonas fluorescens and Bacillus subtilis, and with pond water. The adjustment of pH of the culture or water to 8.8--9.0 facilitates the direct count of the microorganisms, and makes the results more accurate."}
{"id": "PMID:240105", "title": "[Factors influencing the biosynthesis of beta-galactosidase in Alternaria tenuis].", "content": "The effect of pH, carbon sources, and some organic substances on the biosynthesis of beta-galactosidase was studied in Alternaria tenuis on a defined medium that had been optimized by the method of mathematical planning of experiments. Optimal conditions for the production of the enzyme and its liberation into the cultural broth were maintained by adding 2 per cent soya flour to the medium and 0.1 M phosphate-citrate buffer pH 3.0. The production of the enzyme was increased by 3 to 4 times. The biosynthesis of beta-galactosidase by Alternaria tenuis is of an induced nature.", "contents": "[Factors influencing the biosynthesis of beta-galactosidase in Alternaria tenuis]. The effect of pH, carbon sources, and some organic substances on the biosynthesis of beta-galactosidase was studied in Alternaria tenuis on a defined medium that had been optimized by the method of mathematical planning of experiments. Optimal conditions for the production of the enzyme and its liberation into the cultural broth were maintained by adding 2 per cent soya flour to the medium and 0.1 M phosphate-citrate buffer pH 3.0. The production of the enzyme was increased by 3 to 4 times. The biosynthesis of beta-galactosidase by Alternaria tenuis is of an induced nature."}
{"id": "PMID:240106", "title": "[Characteristics of a Mycobacterium mucosum culture oxidizing cholic acid].", "content": "Some physiologo-morphological and biochemical characteristics were studied with the culture of Mycobacterium mucosum 1210 which can assimilate cholic acid as a sole source of carbon. This culture is capable of spontaneous variability. Four variants of the culture were obtained which possessed different rates of the transformation of cholic acid. The variant which formed slimy colonies of pale-yellow colour was the most active. Some morphological modifications of the cells were investigated in the course of cultivation, such as the size, shape and formation of the capsules. Various growth media were tested, and the optimal values of pH were selected.", "contents": "[Characteristics of a Mycobacterium mucosum culture oxidizing cholic acid]. Some physiologo-morphological and biochemical characteristics were studied with the culture of Mycobacterium mucosum 1210 which can assimilate cholic acid as a sole source of carbon. This culture is capable of spontaneous variability. Four variants of the culture were obtained which possessed different rates of the transformation of cholic acid. The variant which formed slimy colonies of pale-yellow colour was the most active. Some morphological modifications of the cells were investigated in the course of cultivation, such as the size, shape and formation of the capsules. Various growth media were tested, and the optimal values of pH were selected."}
{"id": "PMID:240107", "title": "[Effect of low pH values on the chemical composition of a chemostat culture of Bacillus megaterium].", "content": "Inhibition of the growth of Bacillus megaterium was studied in the conditions of chemostat. Inhibition of the growth by hydrogen ions had almost no effect on the content of DNA, RNA, protein and polysaccharides, but the protein-synthesizing activity of RNA changed. The content of polyphosphates, of high and low molecular weight, depended on pH; the relationship was of a non-linear character. The total content of lipids increased with the concentration of hydrogen ions.", "contents": "[Effect of low pH values on the chemical composition of a chemostat culture of Bacillus megaterium]. Inhibition of the growth of Bacillus megaterium was studied in the conditions of chemostat. Inhibition of the growth by hydrogen ions had almost no effect on the content of DNA, RNA, protein and polysaccharides, but the protein-synthesizing activity of RNA changed. The content of polyphosphates, of high and low molecular weight, depended on pH; the relationship was of a non-linear character. The total content of lipids increased with the concentration of hydrogen ions."}
{"id": "PMID:240112", "title": "Changing concepts in the management of hypertension.", "content": "Experience in a hypertension clinic attended by 591 patients over a 13-year period has shown marked changes in the pattern of use of hypotensive agents. Thiazides have been used throughout the period in almost all cases. Methyldopa was used for most patients for almost a decade. Since 1967 there has been a steady increase in the use of beta adrenergic blocking agents, and these are now used for over 60% of patients attending the clinic. Combination beta adrenergic blocking agents with peripheral vasilodators such as hydrallazine and prazosin have provided a very effective means of controlling the blood pressure in moderate and severe hypertension. Prazosin, a new peripheral vasodilator, has been used in the treatment of 295 patients. In most cases it has been used in combination with a thiazide diuretic and beta adrenergic blocking agent. Open studies have demonstrated that this is an effective hypot  .ensive agent. Side effects are few and are counteracted by combination with a beta adrenergic blocking agent. Prazosin and hydrallazine are being compared in double-blind studies.", "contents": "Changing concepts in the management of hypertension. Experience in a hypertension clinic attended by 591 patients over a 13-year period has shown marked changes in the pattern of use of hypotensive agents. Thiazides have been used throughout the period in almost all cases. Methyldopa was used for most patients for almost a decade. Since 1967 there has been a steady increase in the use of beta adrenergic blocking agents, and these are now used for over 60% of patients attending the clinic. Combination beta adrenergic blocking agents with peripheral vasilodators such as hydrallazine and prazosin have provided a very effective means of controlling the blood pressure in moderate and severe hypertension. Prazosin, a new peripheral vasodilator, has been used in the treatment of 295 patients. In most cases it has been used in combination with a thiazide diuretic and beta adrenergic blocking agent. Open studies have demonstrated that this is an effective hypot  .ensive agent. Side effects are few and are counteracted by combination with a beta adrenergic blocking agent. Prazosin and hydrallazine are being compared in double-blind studies."}
{"id": "PMID:240108", "title": "[Comparative characteristics of the ability to coagulate milk in different representatives of the order Actinomycetales].", "content": "The ability to clot milk was studied among 482 cultures of Actinomycetales. The highest activity was manifested by thermophilic actinomycetes, the next come globisporous, white, and gray groups of the genus Actinomyces. Cultures belonging to the genera Mycobacterium and Mycococcus did not clot milk. The ability to clot milk can be used as an additional taxonomic index while studying ray fungi.", "contents": "[Comparative characteristics of the ability to coagulate milk in different representatives of the order Actinomycetales]. The ability to clot milk was studied among 482 cultures of Actinomycetales. The highest activity was manifested by thermophilic actinomycetes, the next come globisporous, white, and gray groups of the genus Actinomyces. Cultures belonging to the genera Mycobacterium and Mycococcus did not clot milk. The ability to clot milk can be used as an additional taxonomic index while studying ray fungi."}
{"id": "PMID:240121", "title": "A tw0-component ribonucleotidyl transferase from E. coli.", "content": "Some properties of an enzyme designated as a two component ribonucleotidyl transferase from E. coli are presented. The enzyme in the presence of magnesium ions catalyzes the synthesis of polyribonucleotide chains using all four nucleoside triphosphates as substrates. The enzyme consists of two components; component A in the presence of Mg2+ catalyzes the synthesis of homo- and heteropolymers using ATP, CTP and UTP but not GTP as substrates. Component B itself does not catalyze any synthesis at all, but its addition to component A affects this component in two ways: quantitatively- the activity of component A considerably increases, and qualitatively- both components together are capable of catalyzing the synthesis of polyribonucleotides consisting of all four ribonucleotides.", "contents": "A tw0-component ribonucleotidyl transferase from E. coli. Some properties of an enzyme designated as a two component ribonucleotidyl transferase from E. coli are presented. The enzyme in the presence of magnesium ions catalyzes the synthesis of polyribonucleotide chains using all four nucleoside triphosphates as substrates. The enzyme consists of two components; component A in the presence of Mg2+ catalyzes the synthesis of homo- and heteropolymers using ATP, CTP and UTP but not GTP as substrates. Component B itself does not catalyze any synthesis at all, but its addition to component A affects this component in two ways: quantitatively- the activity of component A considerably increases, and qualitatively- both components together are capable of catalyzing the synthesis of polyribonucleotides consisting of all four ribonucleotides."}
{"id": "PMID:240122", "title": "Interaction between membrane properties and proteins synthesis in reticulocytes - a two step inhibition of protein synthesis by valinomycin.", "content": "In this work we consider the differential effect of Valinomycin used at different concentrations both on the protein synthesis of reticulocytes and on 42K exchange. We demonstrate that there is a two step action of this antibiotic. At 10(-6)M and below the drug has no effect on the 42K exchange, but it stops, however reversibly, protein synthesis. At 10(-5)M the drug has a very sharp action on the 42K exchange and stops protein synthesis in an irreversible way. Ribosomal population checked by two ways, sucrose gradient and direct counting on E.M. sections shows that at low concentrations of Valinomycin (10(-8)M to 10(-6)M) there is no breakdown of the polysomes which can be detected by either one of these methods. On the contrary, after short incubation with 10(-5)M of Valinomycin the breakdown of ribosomes is very clear, as evidenced by sucrose gradient analysis. By direct ribosomes clusters counting on E.M. sections this breakdown is seen only after long incubation.", "contents": "Interaction between membrane properties and proteins synthesis in reticulocytes - a two step inhibition of protein synthesis by valinomycin. In this work we consider the differential effect of Valinomycin used at different concentrations both on the protein synthesis of reticulocytes and on 42K exchange. We demonstrate that there is a two step action of this antibiotic. At 10(-6)M and below the drug has no effect on the 42K exchange, but it stops, however reversibly, protein synthesis. At 10(-5)M the drug has a very sharp action on the 42K exchange and stops protein synthesis in an irreversible way. Ribosomal population checked by two ways, sucrose gradient and direct counting on E.M. sections shows that at low concentrations of Valinomycin (10(-8)M to 10(-6)M) there is no breakdown of the polysomes which can be detected by either one of these methods. On the contrary, after short incubation with 10(-5)M of Valinomycin the breakdown of ribosomes is very clear, as evidenced by sucrose gradient analysis. By direct ribosomes clusters counting on E.M. sections this breakdown is seen only after long incubation."}
{"id": "PMID:240128", "title": "\"In vivo\" release of endogenous neurotransmitters in cat limbic regions: effect of chlorpromazine and of electrical stimulation.", "content": "The effect of chlorpromazine (10 mg/kg i.v.) on the spontaneous release of endogenous dopamine (DA), noradrenaline (NA) and acetylcholine (ACh) within limbic areas perfused by means of the push-pull cannula was investigated in the gallamine-immobilized cat. Chlorpromazine increased the liberation of DA and NA in the nucleus accumbens septi, indicating blockade of the amine receptors. However, the drug did not change the output of ACh from this nucleus nor from ventral and dorsal hippocampal formations which receive a cholinergic input from the septum as indicated by several published findings and by the increased liberation of ACh after electrical stimulation of the homolateral nucleus medialis septi. These results seem to exclude that cholinergic neurons of some limbic areas mediate the effect of the blockade of DA (and of NA) receptors which is possibly involved in the antipsychotic action of neuroleptic drugs.", "contents": "\"In vivo\" release of endogenous neurotransmitters in cat limbic regions: effect of chlorpromazine and of electrical stimulation. The effect of chlorpromazine (10 mg/kg i.v.) on the spontaneous release of endogenous dopamine (DA), noradrenaline (NA) and acetylcholine (ACh) within limbic areas perfused by means of the push-pull cannula was investigated in the gallamine-immobilized cat. Chlorpromazine increased the liberation of DA and NA in the nucleus accumbens septi, indicating blockade of the amine receptors. However, the drug did not change the output of ACh from this nucleus nor from ventral and dorsal hippocampal formations which receive a cholinergic input from the septum as indicated by several published findings and by the increased liberation of ACh after electrical stimulation of the homolateral nucleus medialis septi. These results seem to exclude that cholinergic neurons of some limbic areas mediate the effect of the blockade of DA (and of NA) receptors which is possibly involved in the antipsychotic action of neuroleptic drugs."}
{"id": "PMID:240129", "title": "Inhibition of striatal dopamine synthesis in rats injected chronically with neuroleptics in their early life.", "content": "3H-dopamine synthesis from L-3,5-3H-tyrosine was reduced in striatal slices of 40 days old rats treated during their early life with neuroleptics. Animals were first injected intra-utero with thioproperazine (5 mg/kg) or with the palmitic ester of pipotiazine (32 mg/kg); the thioproperazine-treated rats were then injected every day from day 1 to day 37; the animals injected with the long acting neuroleptic were injected once more with the drug on day 15 after birth.", "contents": "Inhibition of striatal dopamine synthesis in rats injected chronically with neuroleptics in their early life. 3H-dopamine synthesis from L-3,5-3H-tyrosine was reduced in striatal slices of 40 days old rats treated during their early life with neuroleptics. Animals were first injected intra-utero with thioproperazine (5 mg/kg) or with the palmitic ester of pipotiazine (32 mg/kg); the thioproperazine-treated rats were then injected every day from day 1 to day 37; the animals injected with the long acting neuroleptic were injected once more with the drug on day 15 after birth."}
{"id": "PMID:240130", "title": "Hydrophobic interactions responsible for unspecific binding of morphine-like drugs.", "content": "The unspecific binding of four narcotic analgesics 3H-dihydromorphine, 14C-morphine, 3H-etorphine and 3H-fentanyl to human albumin, human plasma, rabbit plasma and several tissue homogenates from rabbits was investigated using equilibrium dialysis and ultrafiltration. At a drug concentration of 10(-7) M in human plasma, dihydromorphine is bound to an extent of 14%, morphine to 23%, etorphine to 88% and fentanyl to 70%. These differences in binding are due to different degrees of hydrophobic interaction between the drugs investigated and the plasma or tissue components. The hydrophobic interactions are due to the unionized form of the drugs. The ionized form is bound to a negligible extent with all four compounds, possibly in part by ionic mechanism. Binding increased with increasing ionic strength of the protein solution, with raising temperature between 0 degrees C and 37 degrees C and with increasing pH values of the protein solution, features which are characteristic of hydrophobic interactions. Scatchard plots of the binding data, from which the total binding constants nk were derived, indicated high concentrations of binding sites compared with drug concentrations found analgesically effective in vivo.", "contents": "Hydrophobic interactions responsible for unspecific binding of morphine-like drugs. The unspecific binding of four narcotic analgesics 3H-dihydromorphine, 14C-morphine, 3H-etorphine and 3H-fentanyl to human albumin, human plasma, rabbit plasma and several tissue homogenates from rabbits was investigated using equilibrium dialysis and ultrafiltration. At a drug concentration of 10(-7) M in human plasma, dihydromorphine is bound to an extent of 14%, morphine to 23%, etorphine to 88% and fentanyl to 70%. These differences in binding are due to different degrees of hydrophobic interaction between the drugs investigated and the plasma or tissue components. The hydrophobic interactions are due to the unionized form of the drugs. The ionized form is bound to a negligible extent with all four compounds, possibly in part by ionic mechanism. Binding increased with increasing ionic strength of the protein solution, with raising temperature between 0 degrees C and 37 degrees C and with increasing pH values of the protein solution, features which are characteristic of hydrophobic interactions. Scatchard plots of the binding data, from which the total binding constants nk were derived, indicated high concentrations of binding sites compared with drug concentrations found analgesically effective in vivo."}
{"id": "PMID:240131", "title": "Antagonism by d-amphetamine of learning deficits in rats induced by exposure to antipsychotic drugs during early postnatal life.", "content": "The acquisition of a conditioned avoidance response (CAR) was investigated in rats of nursing mothers given pimozide 0.5 mg/kg on days 1, 2, 3, 4, 5, 6, and 7 after delivery. Four weeks after birth, the male litter-mates were tested for CAR acquisition in a two-way avoidance situation or for correct CAR acquisition in a brightness discrimination situation. Offspring of mothers treated with pimozide were markedly inferior in the CAR acquisition in both behavioural situations as compared to those of mothers given glucose. The administration of d-amphetamine 15 min prior to the training session specifically counteracted the behavioural impairment obtained in the offspring of pimozide-treated mothers. The results obtained in the present investigation lend further support to the contention that the behavioural deficits in offspring of nursing mothers treated with neuroleptic agents are due to a developmental disturbance in central catecholamine neurones.", "contents": "Antagonism by d-amphetamine of learning deficits in rats induced by exposure to antipsychotic drugs during early postnatal life. The acquisition of a conditioned avoidance response (CAR) was investigated in rats of nursing mothers given pimozide 0.5 mg/kg on days 1, 2, 3, 4, 5, 6, and 7 after delivery. Four weeks after birth, the male litter-mates were tested for CAR acquisition in a two-way avoidance situation or for correct CAR acquisition in a brightness discrimination situation. Offspring of mothers treated with pimozide were markedly inferior in the CAR acquisition in both behavioural situations as compared to those of mothers given glucose. The administration of d-amphetamine 15 min prior to the training session specifically counteracted the behavioural impairment obtained in the offspring of pimozide-treated mothers. The results obtained in the present investigation lend further support to the contention that the behavioural deficits in offspring of nursing mothers treated with neuroleptic agents are due to a developmental disturbance in central catecholamine neurones."}
{"id": "PMID:240132", "title": "Selectivity for catecholamines of presynaptic alpha-receptors involved in feedback control of sympathetic neurotransmitter secretion in guinea-pig vas deferens.", "content": "The aim of the study was to quantitatively compare the relative affinities of noradrenaline, adrenaline, dopamine and isoprenaline for the, probably neural, receptors mediating feedback control of sympathetic neurotransmitter secretion. The experiments were carried out in isolated superfused field stimulated guinea-pig vas deferens, in which the noradrenaline stores had been labelled by preincubation with tritiated (-)-noradrenaline. Desipramine and normetanephrine were added to prevent rebinding of transmitter. Exogenous noradrenaline was found to cause a dose-dependent and reversible depression of the secretion of tracer noradrenaline evoked by field stimulation. Since the depressing effect was not affected by a ten-fold rise in the desipramine concentration, it seems likely that it was not due to uptake and preferential secretion of unlabelled exogenous noradrenaline, but was truly due to depression of the secretory mechanism. Adrenaline was significantly more potent than noradrenaline, as inhibitor of the secretion of tracer transmitter, while dopamine, at the same molar concentration, was without effect. The beta-agonist isoprenaline did not depress, but rather tended to enhance, the secretion of tracer noradrenaline. It is concluded that the receptors controlling the secretion of noradrenaline from the sympathetic nerves of guinea-pig vas deferens quantitatively-with regard to sensitivity-as well as qualitatively-with regard to order of preference for different catecholamines-resemble the \"classical\" alpha-receptors of e.g. smooth muscle in the same tissue.", "contents": "Selectivity for catecholamines of presynaptic alpha-receptors involved in feedback control of sympathetic neurotransmitter secretion in guinea-pig vas deferens. The aim of the study was to quantitatively compare the relative affinities of noradrenaline, adrenaline, dopamine and isoprenaline for the, probably neural, receptors mediating feedback control of sympathetic neurotransmitter secretion. The experiments were carried out in isolated superfused field stimulated guinea-pig vas deferens, in which the noradrenaline stores had been labelled by preincubation with tritiated (-)-noradrenaline. Desipramine and normetanephrine were added to prevent rebinding of transmitter. Exogenous noradrenaline was found to cause a dose-dependent and reversible depression of the secretion of tracer noradrenaline evoked by field stimulation. Since the depressing effect was not affected by a ten-fold rise in the desipramine concentration, it seems likely that it was not due to uptake and preferential secretion of unlabelled exogenous noradrenaline, but was truly due to depression of the secretory mechanism. Adrenaline was significantly more potent than noradrenaline, as inhibitor of the secretion of tracer transmitter, while dopamine, at the same molar concentration, was without effect. The beta-agonist isoprenaline did not depress, but rather tended to enhance, the secretion of tracer noradrenaline. It is concluded that the receptors controlling the secretion of noradrenaline from the sympathetic nerves of guinea-pig vas deferens quantitatively-with regard to sensitivity-as well as qualitatively-with regard to order of preference for different catecholamines-resemble the \"classical\" alpha-receptors of e.g. smooth muscle in the same tissue."}
{"id": "PMID:240133", "title": "Tyrosine hydroxylase: allosteric activation induced by stimulation of central noradrenergic neurons.", "content": "Electrical stimulation of the rat locus coeruleus cases about a 300% increase in the activity of the tyrosine hydroxylase prepared from the hippocampus on the stimulated side and assayed in the presence of subsaturating concentrations of tyrosine and pteridine cofactor. Addition of calcium or cAMP to soluble preparations of tyrosine hydroxylase isolated from the hippocampus produces a similar activation of tyrosine hydroxylase. The activation of tyrosine hydroxylase produced by calcium is reversed by addition of the calcium chelator, EGTA, while the activation produced by cAMP addition or by electrical stimulation of the locus coeruleus is unaffected by addition of EGTA to the assay medium. The activation of tyrosine hydroxylase produced by electrical stimulation or by addition of calcium or cAMP to the assay medium appears to be mediated in part by alterations in the kinetic properties of the enzyme. All treatment causes the enzyme to have an increased affinity for substrate and pteridine cofactor and a decreased affinity for the endproduct inhibitor, norepinephrine. These results are suggestive that the activation of tyrosine hydroxylase which occurs during periods of increased impulse flow in noradrenergic neurons may be initiated by alterations in calcium fluxes or by changes in the steady state levels of cAMP which accompany neuronal depolarization.", "contents": "Tyrosine hydroxylase: allosteric activation induced by stimulation of central noradrenergic neurons. Electrical stimulation of the rat locus coeruleus cases about a 300% increase in the activity of the tyrosine hydroxylase prepared from the hippocampus on the stimulated side and assayed in the presence of subsaturating concentrations of tyrosine and pteridine cofactor. Addition of calcium or cAMP to soluble preparations of tyrosine hydroxylase isolated from the hippocampus produces a similar activation of tyrosine hydroxylase. The activation of tyrosine hydroxylase produced by calcium is reversed by addition of the calcium chelator, EGTA, while the activation produced by cAMP addition or by electrical stimulation of the locus coeruleus is unaffected by addition of EGTA to the assay medium. The activation of tyrosine hydroxylase produced by electrical stimulation or by addition of calcium or cAMP to the assay medium appears to be mediated in part by alterations in the kinetic properties of the enzyme. All treatment causes the enzyme to have an increased affinity for substrate and pteridine cofactor and a decreased affinity for the endproduct inhibitor, norepinephrine. These results are suggestive that the activation of tyrosine hydroxylase which occurs during periods of increased impulse flow in noradrenergic neurons may be initiated by alterations in calcium fluxes or by changes in the steady state levels of cAMP which accompany neuronal depolarization."}
{"id": "PMID:240134", "title": "Evidence for an involvement of GABA in the mediation of the cerebellar cGMP decrease and the anticonvulsant action diazepam.", "content": "Subcutaneous injections of isoniazid or picrotoxin increase the cerebellar content of 3',5'-cyclic guanosine monophosphate (cGMP) without changing the 3',5'-cyclic adenosine monophosphate cAMP. This increase was dose dependent and the threshold for the cGMP increase was lower than that for convulsions. In cerebellum the increase of cGMP content elicited by isoniazid but not that caused by picrotoxin was paralleled by a decrease of GABA content. Diazepam doses starting from 1.74  mumol/kg intraperitoneally produced a dose dependent decrease of cerebellar cGMP concentration without changing cAMP or GABA content. Smaller doses of diazepam (0.5 mumol/kg i.p.)failed to decrease the basal cerebellar content of cGMP. However, this dose of diazepam antagonized the increase of cGMP produced by isoniazid but not that produced by picrotoxin. Higher doses of diazepam were necessary to block the increase of cerebellar cGMP elicited by picrotoxin. Low doses of diazepam (0.14 mumol/kg) antagonized the convulsions in 50% of the rats injected with 3.3 mmol/kg of isoniazid. The doses of diazepam required to block picrotoxin, pentylenetetrazol or strychnine convulsions were 7, 25 and 40 times higher than those required to block isoniazid convulsions, respectively. Desmethyldiazepam, chloridiazepoxide, oxazepam were also several times more potent in antagonizing isoniazid than picrotoxin, pentylenetetrazol, or strychnine convulsions. In contrast, barbiturates were equipotent against all the convulsants studied. These experiments suggest that diazepam may act in the CNS either by altering the disposition of endogenous GABA or by mimicking the action of GABA at specific synaptic receptors.", "contents": "Evidence for an involvement of GABA in the mediation of the cerebellar cGMP decrease and the anticonvulsant action diazepam. Subcutaneous injections of isoniazid or picrotoxin increase the cerebellar content of 3',5'-cyclic guanosine monophosphate (cGMP) without changing the 3',5'-cyclic adenosine monophosphate cAMP. This increase was dose dependent and the threshold for the cGMP increase was lower than that for convulsions. In cerebellum the increase of cGMP content elicited by isoniazid but not that caused by picrotoxin was paralleled by a decrease of GABA content. Diazepam doses starting from 1.74  mumol/kg intraperitoneally produced a dose dependent decrease of cerebellar cGMP concentration without changing cAMP or GABA content. Smaller doses of diazepam (0.5 mumol/kg i.p.)failed to decrease the basal cerebellar content of cGMP. However, this dose of diazepam antagonized the increase of cGMP produced by isoniazid but not that produced by picrotoxin. Higher doses of diazepam were necessary to block the increase of cerebellar cGMP elicited by picrotoxin. Low doses of diazepam (0.14 mumol/kg) antagonized the convulsions in 50% of the rats injected with 3.3 mmol/kg of isoniazid. The doses of diazepam required to block picrotoxin, pentylenetetrazol or strychnine convulsions were 7, 25 and 40 times higher than those required to block isoniazid convulsions, respectively. Desmethyldiazepam, chloridiazepoxide, oxazepam were also several times more potent in antagonizing isoniazid than picrotoxin, pentylenetetrazol, or strychnine convulsions. In contrast, barbiturates were equipotent against all the convulsants studied. These experiments suggest that diazepam may act in the CNS either by altering the disposition of endogenous GABA or by mimicking the action of GABA at specific synaptic receptors."}
{"id": "PMID:240135", "title": "The beta-adrenergic receptor-adenyl-cyclase system of rat reticulocytes: effects of adrenergic stimulants and inhibitors.", "content": "Non-nucleated red blood cells from rats contain adenyl cyclase, the activity of which is predominantly localized in the reticulocytes. Basal enzyme activities in membrane preparations from reticulocyte-rich blood (pretreatment of rats with acetyl-phenylhydrazide: about 60% reticuloytes) are about 5 times higher than in preparations from reticulocyte-poor blood (untreated animals: 2-3% reticulocytes). The enzyme activities are stimulated 10-fold by sodium fluoride (10(-2)M) and 6 to 8-fold by isoprenaline (10(-4)M). Adenyl cyclase activities in membrane preparations from reticulocyte-rich and reticulocyte-poor blood can be ascribed to identical enzymes since identical apparent Km (ATP; 3 times 10(-4)M, Ka (isoprenaline; 3 times 10(-6)M) and Ki (propranolol vs. isoprenaline; 3 times 10(-7)M) values were obtained in both preparations. Besides NaF, only phenylethanolamine derivatives with beta-adrenergic receptor stimulant properties were effective as stimulators of adenyl cyclase activity. The affinities (apparent Ka values) of the investigated compounds decreased in the order isoprenaline--hexoprenaline--fenoterol--salbutamol--adrenaline--terbutalin--noradrenaline--phenylephrine. For maximal intrinsic activity, the catechol structure was essential; the relative intrinsic activities of resorcinol derivatives did not exceed 0.6. The isoprenaline-stimulated adenyl cyclase activities in erythrocyte membrane preparations were competitively inhibited by beta-adrenergic blocking drugs, the affinities (apparent Ki values) decreasing in the order prindolol--penbutolol--propranolol--practolol. The dextrorotatory enantiomers of penbutolol and propranolol were 1/100 to 1/200 as active as the resp. levorotatory enantiomers. From experiments with alpha-adrenergic agonists (e.g. phenylephrine) and antagonists (e.g. phentolamine), it is concluded that alpha-adrenergic receptors do not interfere with the beta-adrenergically-mediated cAMP formation in these particular membranes. A variety of hormones and drugs known to stimulate denyl cyclase activities in various tissues, e. g. ACTH, glucagon, STH, erythropoietin, prostaglandin E1 etc. did not affect adenyl cyclase activity in reticulocyte-rich erythrocyte membrane preparations. In contrast to adenyl cyclase activity, phosphodiesterase activities in erythrocyte membrane and cytoplasmic fractions were only twice as high in reticulocyte-rich as in reticulocyte-poor preparations. From the experiments described, it is obvious that the adenyl cyclase of the rat reticulocyte is subject to monovalent-hormonal, i.e. beta-sympathomimetic stimulation. Moreover, the premature red blood cell provides a useful model for quantitative studies of the interaction of drugs with the beta-adrenergic receptor.", "contents": "The beta-adrenergic receptor-adenyl-cyclase system of rat reticulocytes: effects of adrenergic stimulants and inhibitors. Non-nucleated red blood cells from rats contain adenyl cyclase, the activity of which is predominantly localized in the reticulocytes. Basal enzyme activities in membrane preparations from reticulocyte-rich blood (pretreatment of rats with acetyl-phenylhydrazide: about 60% reticuloytes) are about 5 times higher than in preparations from reticulocyte-poor blood (untreated animals: 2-3% reticulocytes). The enzyme activities are stimulated 10-fold by sodium fluoride (10(-2)M) and 6 to 8-fold by isoprenaline (10(-4)M). Adenyl cyclase activities in membrane preparations from reticulocyte-rich and reticulocyte-poor blood can be ascribed to identical enzymes since identical apparent Km (ATP; 3 times 10(-4)M, Ka (isoprenaline; 3 times 10(-6)M) and Ki (propranolol vs. isoprenaline; 3 times 10(-7)M) values were obtained in both preparations. Besides NaF, only phenylethanolamine derivatives with beta-adrenergic receptor stimulant properties were effective as stimulators of adenyl cyclase activity. The affinities (apparent Ka values) of the investigated compounds decreased in the order isoprenaline--hexoprenaline--fenoterol--salbutamol--adrenaline--terbutalin--noradrenaline--phenylephrine. For maximal intrinsic activity, the catechol structure was essential; the relative intrinsic activities of resorcinol derivatives did not exceed 0.6. The isoprenaline-stimulated adenyl cyclase activities in erythrocyte membrane preparations were competitively inhibited by beta-adrenergic blocking drugs, the affinities (apparent Ki values) decreasing in the order prindolol--penbutolol--propranolol--practolol. The dextrorotatory enantiomers of penbutolol and propranolol were 1/100 to 1/200 as active as the resp. levorotatory enantiomers. From experiments with alpha-adrenergic agonists (e.g. phenylephrine) and antagonists (e.g. phentolamine), it is concluded that alpha-adrenergic receptors do not interfere with the beta-adrenergically-mediated cAMP formation in these particular membranes. A variety of hormones and drugs known to stimulate denyl cyclase activities in various tissues, e. g. ACTH, glucagon, STH, erythropoietin, prostaglandin E1 etc. did not affect adenyl cyclase activity in reticulocyte-rich erythrocyte membrane preparations. In contrast to adenyl cyclase activity, phosphodiesterase activities in erythrocyte membrane and cytoplasmic fractions were only twice as high in reticulocyte-rich as in reticulocyte-poor preparations. From the experiments described, it is obvious that the adenyl cyclase of the rat reticulocyte is subject to monovalent-hormonal, i.e. beta-sympathomimetic stimulation. Moreover, the premature red blood cell provides a useful model for quantitative studies of the interaction of drugs with the beta-adrenergic receptor."}
{"id": "PMID:240136", "title": "Acute and subacute effects of neuroleptics dopamine synthesis and release in the rat striatum.", "content": "The effects of acute and subacute treatments with moderate doses of thioproperazine and haloperidol on dopamine synthesis and release have been examined in rat striatal slices. Synthesis and release of dopamine were determined by measuring the rate of formation of 3H-H2O during the conversion of L3,5-3H-tyrosine into 3H-Dopa and the accumulation of newly synthesized 3H-dopamine in striatal slices and their incubating medium. Possible effects of the treatments on tyrosine striatal levels or tyrosine specific activity were also investigated. Dopamine synthesis rate was markedly accelerated 2.5 hrs after the acute injection of thioproperazine, but was equal to control levels 24 hrs later. The effects of thioproperazine and haloperidol were thus determined 2.5 and 24 hrs after an acute injection and following the last injection of a repeated daily treatment of 11 days. Dopamine synthesis and release were still markedly increased 2.5 hrs after the last injection of the subacute neuroleptic treatments when compared to controls, but these effects were less pronounced than those observed 2.5 hrs after an acute injection of either drug. Conversely, dopamine synthesis and release were significantly decreased 24 hrs after the last injection of the subacute neuroleptic treatments when compared to controls. Two hypotheses are proposed to explain the changes in dopamine synthesis induced by repeated treatments with neurolptics.", "contents": "Acute and subacute effects of neuroleptics dopamine synthesis and release in the rat striatum. The effects of acute and subacute treatments with moderate doses of thioproperazine and haloperidol on dopamine synthesis and release have been examined in rat striatal slices. Synthesis and release of dopamine were determined by measuring the rate of formation of 3H-H2O during the conversion of L3,5-3H-tyrosine into 3H-Dopa and the accumulation of newly synthesized 3H-dopamine in striatal slices and their incubating medium. Possible effects of the treatments on tyrosine striatal levels or tyrosine specific activity were also investigated. Dopamine synthesis rate was markedly accelerated 2.5 hrs after the acute injection of thioproperazine, but was equal to control levels 24 hrs later. The effects of thioproperazine and haloperidol were thus determined 2.5 and 24 hrs after an acute injection and following the last injection of a repeated daily treatment of 11 days. Dopamine synthesis and release were still markedly increased 2.5 hrs after the last injection of the subacute neuroleptic treatments when compared to controls, but these effects were less pronounced than those observed 2.5 hrs after an acute injection of either drug. Conversely, dopamine synthesis and release were significantly decreased 24 hrs after the last injection of the subacute neuroleptic treatments when compared to controls. Two hypotheses are proposed to explain the changes in dopamine synthesis induced by repeated treatments with neurolptics."}
{"id": "PMID:240140", "title": "[4-allyloxy-3-chlorophenyl-acetic acid (alclofenac) in the treatment of painful arthroses in the aged. Double-blind controlled clinical trial].", "content": "The antiarthrosic effectiveness with respect to spontaneous pain upon movement and pressure, of alclofenac (4-allyloxy-3-chlorophenyl-acetic acid) was tested in a homogeneous group of elderly patients and compared with orally administered indomethacin. The research was carried out in strictly controlled, double-blind experimental conditions. The results obtained suggest that 500 mg of the new anti-inflammatory analgesic have the same action as 25 mg of indomethacin but with a lower incidence of the side effects common to all anti-inflammatory substances. Thanks to its good tolerability and high effectiveness, the new drug should be of considerable utility in the treatment of arthrosis in the elderly and in painful, inflammatory complications.", "contents": "[4-allyloxy-3-chlorophenyl-acetic acid (alclofenac) in the treatment of painful arthroses in the aged. Double-blind controlled clinical trial]. The antiarthrosic effectiveness with respect to spontaneous pain upon movement and pressure, of alclofenac (4-allyloxy-3-chlorophenyl-acetic acid) was tested in a homogeneous group of elderly patients and compared with orally administered indomethacin. The research was carried out in strictly controlled, double-blind experimental conditions. The results obtained suggest that 500 mg of the new anti-inflammatory analgesic have the same action as 25 mg of indomethacin but with a lower incidence of the side effects common to all anti-inflammatory substances. Thanks to its good tolerability and high effectiveness, the new drug should be of considerable utility in the treatment of arthrosis in the elderly and in painful, inflammatory complications."}
{"id": "PMID:240141", "title": "[Study of the tolerability and effectiveness of a new sleep-inducing preparation].", "content": "Flurazepam hydrochloride was experimented on 43 patients aged 33-83 yr with various forms of insomnia over a period of 4 to 23 days (mean 11.66). There were no changes in the laboratory data and gastroenteric tolerance was also excellent. Chi-square analysis showed that both the quantity and quality of sleep were significantly improved (P less than 0,001). There was no evidence of assuefaction or withdrawal symptoms.", "contents": "[Study of the tolerability and effectiveness of a new sleep-inducing preparation]. Flurazepam hydrochloride was experimented on 43 patients aged 33-83 yr with various forms of insomnia over a period of 4 to 23 days (mean 11.66). There were no changes in the laboratory data and gastroenteric tolerance was also excellent. Chi-square analysis showed that both the quantity and quality of sleep were significantly improved (P less than 0,001). There was no evidence of assuefaction or withdrawal symptoms."}
{"id": "PMID:240142", "title": "Successful management of severe aortocaval compression in twin pregnancy.", "content": "In a patient with severe aortocaval compression, simultaneous brachial and femoral blood pressure measurements demonstrated the need for a 30 degrees left-down tilt to avoid significant obstruction of the vessels. When emergency cesarean section became necessary, proper positioning of the patient was readily accomplished.", "contents": "Successful management of severe aortocaval compression in twin pregnancy. In a patient with severe aortocaval compression, simultaneous brachial and femoral blood pressure measurements demonstrated the need for a 30 degrees left-down tilt to avoid significant obstruction of the vessels. When emergency cesarean section became necessary, proper positioning of the patient was readily accomplished."}
{"id": "PMID:240144", "title": "Acute neonatal nonketotic hyperglycinemia: normal propionate and methylmalonate metabolism.", "content": "Propionyl-CoA carboxylase and combined methylmalonyl-CoA (MMA-CoA) racemase and -mutase activities were studied in liver and fibroblasts of two patients with the acute neonatal form of nonketotic hyperglycemia. In all experiments, these enzyme activities studied in tissues of the patients were within the range of healthy control subjects, whereas no propionyl-CoA carboxylase activity was measurable in the fibroblasts of a patient with propionic acidemia. Subcellular fractionation of liver and fibroblasts indicated that the normal amounts of MMA-CoA found after incubation of whole tissue homogenate were formed by propionyl-CoA carboxylase, a mitochondrial enzyme, and not be acetyl-CoA carboxylase, which theoretically could also be involved in the carboxylation of propionyl-CoA. From the above data as well as from clinical and biochemical observations in three patients, it was concluded that there exists a true nonketotic hyperglycinemia which is not related etiologically to the different disorders of the ketotic hyperglycinemia syndrome. True nonketotic hyperglycinemia is not associated with ketoacidosis even after loading with propionate- and MMA precursors. It must be distinguished by exclusion from mild forms of the ketotic hyperglycinemia syndrome which may present clinically as hyperglycinemia without ketosis.", "contents": "Acute neonatal nonketotic hyperglycinemia: normal propionate and methylmalonate metabolism. Propionyl-CoA carboxylase and combined methylmalonyl-CoA (MMA-CoA) racemase and -mutase activities were studied in liver and fibroblasts of two patients with the acute neonatal form of nonketotic hyperglycemia. In all experiments, these enzyme activities studied in tissues of the patients were within the range of healthy control subjects, whereas no propionyl-CoA carboxylase activity was measurable in the fibroblasts of a patient with propionic acidemia. Subcellular fractionation of liver and fibroblasts indicated that the normal amounts of MMA-CoA found after incubation of whole tissue homogenate were formed by propionyl-CoA carboxylase, a mitochondrial enzyme, and not be acetyl-CoA carboxylase, which theoretically could also be involved in the carboxylation of propionyl-CoA. From the above data as well as from clinical and biochemical observations in three patients, it was concluded that there exists a true nonketotic hyperglycinemia which is not related etiologically to the different disorders of the ketotic hyperglycinemia syndrome. True nonketotic hyperglycinemia is not associated with ketoacidosis even after loading with propionate- and MMA precursors. It must be distinguished by exclusion from mild forms of the ketotic hyperglycinemia syndrome which may present clinically as hyperglycinemia without ketosis."}
{"id": "PMID:240147", "title": "Early growth and development in low-birthweight infants following treatment in an intensive care nursery.", "content": "Sixty-seven appropriate-for-date infants with gestations less than 33 weeks were followed for 12 months after their term dates. All had been born after September 1970. None received hypercaloric alimentation as neonates. Growth from the expected date of delivery was compared with that of 24 normal full-term infants and with accepted growth standards. The boys did not differ from the controls or the standard in mean weight, length, and head circumference, in weight and height indices, or in velocity of weight and linear growth. The girls had a slower velocity of weight growth for the first six months and had significantly lower weight indices at 12 months than did their controls. Velocity of linear growth, height indices, and mean length and head circumference for the girls were similar to those of the control standards. Gross central nervous system defects occurred in 22.5% of the boys but in none of the girls. More than one half of the abnormalities were hydrocephaly. The mean post-conceptional developmental quotient was 110 for the girls and 108 for the boys.", "contents": "Early growth and development in low-birthweight infants following treatment in an intensive care nursery. Sixty-seven appropriate-for-date infants with gestations less than 33 weeks were followed for 12 months after their term dates. All had been born after September 1970. None received hypercaloric alimentation as neonates. Growth from the expected date of delivery was compared with that of 24 normal full-term infants and with accepted growth standards. The boys did not differ from the controls or the standard in mean weight, length, and head circumference, in weight and height indices, or in velocity of weight and linear growth. The girls had a slower velocity of weight growth for the first six months and had significantly lower weight indices at 12 months than did their controls. Velocity of linear growth, height indices, and mean length and head circumference for the girls were similar to those of the control standards. Gross central nervous system defects occurred in 22.5% of the boys but in none of the girls. More than one half of the abnormalities were hydrocephaly. The mean post-conceptional developmental quotient was 110 for the girls and 108 for the boys."}
{"id": "PMID:240148", "title": "Assisted ventilation in infants with meconium aspiration syndrome.", "content": "In a retrospective analysis of infants born with meconium staining over an 18-month period at Cook County Hospital, 32 infants met two of the three criteria for the diagnosis of meconium aspiration syndrome: (1) history of meconium in the oropharynx or trachea; (2) clinical evidence of respiratory distress; and (3) x-ray evidence of aspiration pneumonia. Seventeen infants developed respiratory failure; nine of these infants died. One infant without respiratory failure died of sepsis. Analysis of sequential arterial blood pH and gas tension showed that nonsurviving infants had persistently high PCO2 and A-a gradient in spite of initiation of assisted ventilation. These changes seem to be related to severe right-to-left shunting and ventilation perfusion abnormalities. The data further suggest that asphyxia and acidosis occur well before the infant is born and that intrapartum monitoring to recognize fetal asphyxia may help in improving morbidity and mortality from meconium aspiration syndrome.", "contents": "Assisted ventilation in infants with meconium aspiration syndrome. In a retrospective analysis of infants born with meconium staining over an 18-month period at Cook County Hospital, 32 infants met two of the three criteria for the diagnosis of meconium aspiration syndrome: (1) history of meconium in the oropharynx or trachea; (2) clinical evidence of respiratory distress; and (3) x-ray evidence of aspiration pneumonia. Seventeen infants developed respiratory failure; nine of these infants died. One infant without respiratory failure died of sepsis. Analysis of sequential arterial blood pH and gas tension showed that nonsurviving infants had persistently high PCO2 and A-a gradient in spite of initiation of assisted ventilation. These changes seem to be related to severe right-to-left shunting and ventilation perfusion abnormalities. The data further suggest that asphyxia and acidosis occur well before the infant is born and that intrapartum monitoring to recognize fetal asphyxia may help in improving morbidity and mortality from meconium aspiration syndrome."}
{"id": "PMID:240149", "title": "Medex: a time-motion study.", "content": "Six Medex working with family practitioners were followed by an observer for a total of 18 days to gain an objective profile of how Medex spent their workday. Medex on the average spent 30% of their time with office patients and saw 38% of all office patients. Medex saw between 25% and 100% of all pediatric office patients and spent on the average 37% of their office patient time with pediatric patients. On the average, Medex saw 8 pediatric and 11 adult office patients per day. Well-child examinations, the largest pediatric diagnostic category, accounted for 30% of Medex pediatric office patient time. Minor surgery accounted for the second largest portion of pediatric office patient time (21%) while respiratory illness ranked third (11%). In view of the increasing role family practitioners and their assistants will undoubtedly play in the provision of child health care, pediatricians are urged to work closely with family physicians in developing and implementing health care services for children.", "contents": "Medex: a time-motion study. Six Medex working with family practitioners were followed by an observer for a total of 18 days to gain an objective profile of how Medex spent their workday. Medex on the average spent 30% of their time with office patients and saw 38% of all office patients. Medex saw between 25% and 100% of all pediatric office patients and spent on the average 37% of their office patient time with pediatric patients. On the average, Medex saw 8 pediatric and 11 adult office patients per day. Well-child examinations, the largest pediatric diagnostic category, accounted for 30% of Medex pediatric office patient time. Minor surgery accounted for the second largest portion of pediatric office patient time (21%) while respiratory illness ranked third (11%). In view of the increasing role family practitioners and their assistants will undoubtedly play in the provision of child health care, pediatricians are urged to work closely with family physicians in developing and implementing health care services for children."}
{"id": "PMID:240152", "title": "[Treatment of bone marrow aplasia by allogenic bone marrow grafts].", "content": "Three patients with severe aplastic anemia were treated by bone marrow transplantation using the method described by Santos and Thomas. Two of the patients, both successfully grafted have survived for more than 5 and 6 months respectively. Chimerism was proved by cytogenetic analysis and erythrocytic phenotypes. In one case, a severe graft versus host reaction was cured with ATG and prednisone. Graft rejection in the third case was related to the immunisation caused by many previous transfusions. Although bone marrow grafting is limited by the necessity of using a matched sibling as donor, its success this far is very encouraging and represents a new hope for the treatment of aplastic anemia.", "contents": "[Treatment of bone marrow aplasia by allogenic bone marrow grafts]. Three patients with severe aplastic anemia were treated by bone marrow transplantation using the method described by Santos and Thomas. Two of the patients, both successfully grafted have survived for more than 5 and 6 months respectively. Chimerism was proved by cytogenetic analysis and erythrocytic phenotypes. In one case, a severe graft versus host reaction was cured with ATG and prednisone. Graft rejection in the third case was related to the immunisation caused by many previous transfusions. Although bone marrow grafting is limited by the necessity of using a matched sibling as donor, its success this far is very encouraging and represents a new hope for the treatment of aplastic anemia."}
{"id": "PMID:240153", "title": "[Post-hepatitic aplasia treated by grafts of allogenic bone marrow. Remission for more than 2 years. Persistance of a total hematopoietic chimera. Graft versus host reaction].", "content": "A successfull bone marrow transplant was achieved in a case of post hepatitic aplastic anemia after cyclophosphamide immunosuppression. Caryotype analysis, erythrocytic phenotype and IgG Gm allotype demonstrated evidence of complete chimerism. Anti-thymocyte serum undoubtly was able to suppress a life threatening episode of graft versus host reaction. Severe long lasting skin lesions are now persisting 2 years after the graft.", "contents": "[Post-hepatitic aplasia treated by grafts of allogenic bone marrow. Remission for more than 2 years. Persistance of a total hematopoietic chimera. Graft versus host reaction]. A successfull bone marrow transplant was achieved in a case of post hepatitic aplastic anemia after cyclophosphamide immunosuppression. Caryotype analysis, erythrocytic phenotype and IgG Gm allotype demonstrated evidence of complete chimerism. Anti-thymocyte serum undoubtly was able to suppress a life threatening episode of graft versus host reaction. Severe long lasting skin lesions are now persisting 2 years after the graft."}
{"id": "PMID:240157", "title": "The spectrum of systemic vasculitis: a classification to aid diagnosis.", "content": "Determining the cause of systemic vasculitis can be facilitated by a clinicopathologic classification of the syndrome. The considerations in differential diagnosis include periarteritis nodosa, leukocytoclastic angiitis (hypersensitivity angiitis, Schonlein-Henoch purpura, other disease-associated vasculitis), Wegener's granulomatosis, allergic granulomatosis (granulomatous angiitis), and giant cell arteritis.", "contents": "The spectrum of systemic vasculitis: a classification to aid diagnosis. Determining the cause of systemic vasculitis can be facilitated by a clinicopathologic classification of the syndrome. The considerations in differential diagnosis include periarteritis nodosa, leukocytoclastic angiitis (hypersensitivity angiitis, Schonlein-Henoch purpura, other disease-associated vasculitis), Wegener's granulomatosis, allergic granulomatosis (granulomatous angiitis), and giant cell arteritis."}
{"id": "PMID:240158", "title": "Respiratory problems complicating burn injury: recognition, assessment, and treatment.", "content": "Postburn pulmonary injury is a common and frequently overlooked concomitant of burn injury. The lesion may be secondary to direct damage to the respiratory apparatus from the inhalation of smoke or of toxic or superheated chemicals or from mechanical mechanisms or it may be secondary to indirect damage from hypovolemia, shock, central nervous system disturbances, or drug usage. Therapy comprises establishment of a clear airway and administration of humidity and oxygen in amounts appropriate to maintain adequate blood oxygen tension and pH. Sequential monitoring of oxygen and pH status is required. The diagnosis of postburn pulmonary injury is made on clinical grounds, and sequential management of the patient, closely supported by laboratory studies, is essential. Surface decompression of the thorax, antibiotics given systemically, and sequentially increasing respiratory support (with later de-escalation) may be needed.", "contents": "Respiratory problems complicating burn injury: recognition, assessment, and treatment. Postburn pulmonary injury is a common and frequently overlooked concomitant of burn injury. The lesion may be secondary to direct damage to the respiratory apparatus from the inhalation of smoke or of toxic or superheated chemicals or from mechanical mechanisms or it may be secondary to indirect damage from hypovolemia, shock, central nervous system disturbances, or drug usage. Therapy comprises establishment of a clear airway and administration of humidity and oxygen in amounts appropriate to maintain adequate blood oxygen tension and pH. Sequential monitoring of oxygen and pH status is required. The diagnosis of postburn pulmonary injury is made on clinical grounds, and sequential management of the patient, closely supported by laboratory studies, is essential. Surface decompression of the thorax, antibiotics given systemically, and sequentially increasing respiratory support (with later de-escalation) may be needed."}
{"id": "PMID:240159", "title": "Lipid biosynthesis in the chick. A consideration of site of synthesis, influence of diet and possible regulatory mechanisms.", "content": "Studies in vitro and with intact chicks support the view that liver is the major site of lipid biosynthesis in the chicken. Adipose tissue is relatively unimportant as a site of fatty acid biosynthesis in this species although it does have the ability to esterify fatty acids to triglycerides. The available evidence, therefore, suggests that in the chicken, and presumably other avian species, fatty acids are synthesized in liver and are transported as triglycerides in the plasma low-density lipoproteins to the adipose tissue for storage. Fasting, even for short periods of time, markedly depresses the capacity for hepatic lipogenesis in the chick. Food restriction for 2 hr. depresses hepatic lipogenesis by about 90% and refeeding for 1 hr./or/the intravenous administration of glucose or fructose restores the lipogenic capacity. Feeding diets high in fat or protein cannot be adequately explained on the basis of the reduction of dietary carbohydrate which accompanies increased dietary protein or fat levels. Dietary fat and protein appear to exert their effects on hepatic lipid synthesis by different mechanisms. The depression in hepatic fatty acid synthesis brought about by fasting or fat-feeding is accompanied, and probably preceded, by an increased plasma free fatty acid level. Under these conditions hepatic fatty-acyl CoA levels increase while free CoA levels are reduced. Long-chain acyl CoA derivatives are capable of inhibiting acetyl CoA carboxylase activity as well as citrate transport. The reduced availability of free CoA may limit the citrate cleavage reaction. Dietary alterations influence the hepatic lactate-pyruvate ratio of chicks, however the changes observed are not always consistent with the changes observed in rat liver. Chicks fed high-protein diets have a decreased hepatic lactate/pyruvate ratio indicative of a more oxidized cytoplasmic environment. This change in redox state may be associated with control of fatty acid synthesis in chicks fed high-protein diets. Thyroxine and glucagon affect hepatic fatty acid synthesis in the chick, however insulin appears to play a lesser role.", "contents": "Lipid biosynthesis in the chick. A consideration of site of synthesis, influence of diet and possible regulatory mechanisms. Studies in vitro and with intact chicks support the view that liver is the major site of lipid biosynthesis in the chicken. Adipose tissue is relatively unimportant as a site of fatty acid biosynthesis in this species although it does have the ability to esterify fatty acids to triglycerides. The available evidence, therefore, suggests that in the chicken, and presumably other avian species, fatty acids are synthesized in liver and are transported as triglycerides in the plasma low-density lipoproteins to the adipose tissue for storage. Fasting, even for short periods of time, markedly depresses the capacity for hepatic lipogenesis in the chick. Food restriction for 2 hr. depresses hepatic lipogenesis by about 90% and refeeding for 1 hr./or/the intravenous administration of glucose or fructose restores the lipogenic capacity. Feeding diets high in fat or protein cannot be adequately explained on the basis of the reduction of dietary carbohydrate which accompanies increased dietary protein or fat levels. Dietary fat and protein appear to exert their effects on hepatic lipid synthesis by different mechanisms. The depression in hepatic fatty acid synthesis brought about by fasting or fat-feeding is accompanied, and probably preceded, by an increased plasma free fatty acid level. Under these conditions hepatic fatty-acyl CoA levels increase while free CoA levels are reduced. Long-chain acyl CoA derivatives are capable of inhibiting acetyl CoA carboxylase activity as well as citrate transport. The reduced availability of free CoA may limit the citrate cleavage reaction. Dietary alterations influence the hepatic lactate-pyruvate ratio of chicks, however the changes observed are not always consistent with the changes observed in rat liver. Chicks fed high-protein diets have a decreased hepatic lactate/pyruvate ratio indicative of a more oxidized cytoplasmic environment. This change in redox state may be associated with control of fatty acid synthesis in chicks fed high-protein diets. Thyroxine and glucagon affect hepatic fatty acid synthesis in the chick, however insulin appears to play a lesser role."}
{"id": "PMID:240160", "title": "Radical mechanisms for 1,5-dihydroflavin reduction of carbonyl compounds.", "content": "A discussion of the expected mechanism of radical reduction of carbonyl compounds by dihydroflavin as it relates to the structure of the carbonyl compound is provided. Factors which must be taken into account are the free energies of formation of the radical anions (CR2O), THE ACIDITY OF THE CONJUGATE ACID OF THE CARBONYL FUNCTION (R2C negative charge OH), and the stability of the carbanion species of the product [(-)CR2(OH)]. It is proposed that in those instances where the product alcohol can flavin radical to CR2O or CR2OH occurs, otherwise H transfer is the terminal step for dihydroflavin reductions. The free energy of formation of the radical species CH2OH obtained by acid-catalyzed electron transfer from dihydroflavin (Fred) to formaldehyde is shown to be less than the experimentally determined free energy of activation (increment F is not equal to exp) for the reduction of formaldehyde by dihydroflavin (i.e., Fred plus CH2O leads to Fox plus CH2OH). Therefore, the radical pair composed of dihydroflavin radical species serve as an intermediate in the reduction. Our proposed mechanism is: Fred plus CH2O ka[H3O] forms k-a[H2O] Frad CH2OH leads to kc Fox plus CH3OH. The value of kaah/k-a has been obtained from the calculated standard potential Eo' for Fred plus CH2O plus H forms Frad plus CH2OH. Assuming ka to represent a two-step process (i.e., Fred plus CH2O plus H k'a forms k'-a Fred plus CH2OH kb forms k-b Frad CH2OH, where ka equals (k'akb)/(k'-ak-b), the value of k'-a will equal 10-10 M-minus 1 sec-minus 1 and kb 10-9 M-minus 1 sec-minus 1. From k'a/k'-a and kb there can be computed the expected value of increment F is not equal to calc as a function of pH. Comparison of increment F is not equal to calc to increment F is not equal to exp reveals that increment F is not equal to calc varies from increment F is not equal to exp by only about 2kcal mol-minus 1 (8.4 kJ mol-minus 1) between pH 5 and 9. Similar considerations establish that radical intermediates should serve eminently well in dihydroflavin reduction of ethyl pyruvate, pyruvic acid, etc. In these cases, 1 e transfer should compete with H transfer to yield the carbanions as the immediate products. Similar comparisons suggest that dihydronicotinamide reduction proceeds via RPyH plus C negative charge O forms RPyH plus C-0minus +H forms -H RPyH plus C-OH forms RPy plus HC-OH.", "contents": "Radical mechanisms for 1,5-dihydroflavin reduction of carbonyl compounds. A discussion of the expected mechanism of radical reduction of carbonyl compounds by dihydroflavin as it relates to the structure of the carbonyl compound is provided. Factors which must be taken into account are the free energies of formation of the radical anions (CR2O), THE ACIDITY OF THE CONJUGATE ACID OF THE CARBONYL FUNCTION (R2C negative charge OH), and the stability of the carbanion species of the product [(-)CR2(OH)]. It is proposed that in those instances where the product alcohol can flavin radical to CR2O or CR2OH occurs, otherwise H transfer is the terminal step for dihydroflavin reductions. The free energy of formation of the radical species CH2OH obtained by acid-catalyzed electron transfer from dihydroflavin (Fred) to formaldehyde is shown to be less than the experimentally determined free energy of activation (increment F is not equal to exp) for the reduction of formaldehyde by dihydroflavin (i.e., Fred plus CH2O leads to Fox plus CH2OH). Therefore, the radical pair composed of dihydroflavin radical species serve as an intermediate in the reduction. Our proposed mechanism is: Fred plus CH2O ka[H3O] forms k-a[H2O] Frad CH2OH leads to kc Fox plus CH3OH. The value of kaah/k-a has been obtained from the calculated standard potential Eo' for Fred plus CH2O plus H forms Frad plus CH2OH. Assuming ka to represent a two-step process (i.e., Fred plus CH2O plus H k'a forms k'-a Fred plus CH2OH kb forms k-b Frad CH2OH, where ka equals (k'akb)/(k'-ak-b), the value of k'-a will equal 10-10 M-minus 1 sec-minus 1 and kb 10-9 M-minus 1 sec-minus 1. From k'a/k'-a and kb there can be computed the expected value of increment F is not equal to calc as a function of pH. Comparison of increment F is not equal to calc to increment F is not equal to exp reveals that increment F is not equal to calc varies from increment F is not equal to exp by only about 2kcal mol-minus 1 (8.4 kJ mol-minus 1) between pH 5 and 9. Similar considerations establish that radical intermediates should serve eminently well in dihydroflavin reduction of ethyl pyruvate, pyruvic acid, etc. In these cases, 1 e transfer should compete with H transfer to yield the carbanions as the immediate products. Similar comparisons suggest that dihydronicotinamide reduction proceeds via RPyH plus C negative charge O forms RPyH plus C-0minus +H forms -H RPyH plus C-OH forms RPy plus HC-OH."}
{"id": "PMID:240174", "title": "Studies on the stability of injectable solutions of some phenothiazines. Part 1: Effects of pH and buffer systems.", "content": "The stability of phenothiazines is affected by the pH-value of the solution. At the pH-values of maximum stability, triflupromazine hydrochloride and chlorpromazine hydrochloride are more stable than promazine hydrochloride. The stability of chlorpromazine hydrochloride in the S\u00f6rensen's phosphate buffer is slightly higher than that in the McIlvaine's citric acid-phosphate buffer system. On the other hand, the stbility of promazine hydrochloride and triflupromazine hydrochloride in the latter buffer system is slightly higher than that in the former one.", "contents": "Studies on the stability of injectable solutions of some phenothiazines. Part 1: Effects of pH and buffer systems. The stability of phenothiazines is affected by the pH-value of the solution. At the pH-values of maximum stability, triflupromazine hydrochloride and chlorpromazine hydrochloride are more stable than promazine hydrochloride. The stability of chlorpromazine hydrochloride in the S\u00f6rensen's phosphate buffer is slightly higher than that in the McIlvaine's citric acid-phosphate buffer system. On the other hand, the stbility of promazine hydrochloride and triflupromazine hydrochloride in the latter buffer system is slightly higher than that in the former one."}
{"id": "PMID:240175", "title": "Studies on the stability of injectable solutions of some phenothiazines. Part 2: Effect of chelating agents and antioxidants.", "content": "Chelating agents (disodium EDTA, DTPA, HEDTA and NTA) exhibit a stabilizing action towards phenothiazines to different extents. This could be correlated to the stability constants of their metal chelates as well as to the dependency of these constants on the pH-value of the solution. Antioxidants (sodium bisulphite, sodium dithionite, and sodium metabisulphite) also exert a stabilizing effect which could be correlated--in the first place--to the pH-value of the solution. The sulphur content of the antioxidant might also be relevant to such an effect.", "contents": "Studies on the stability of injectable solutions of some phenothiazines. Part 2: Effect of chelating agents and antioxidants. Chelating agents (disodium EDTA, DTPA, HEDTA and NTA) exhibit a stabilizing action towards phenothiazines to different extents. This could be correlated to the stability constants of their metal chelates as well as to the dependency of these constants on the pH-value of the solution. Antioxidants (sodium bisulphite, sodium dithionite, and sodium metabisulphite) also exert a stabilizing effect which could be correlated--in the first place--to the pH-value of the solution. The sulphur content of the antioxidant might also be relevant to such an effect."}
{"id": "PMID:240178", "title": "The alpha-chain-termination mutants and their relation to the alpha-thalassaemias.", "content": "The structure, synthesis, genetic transmission, clinical associations and distribution of the elongated alpha-chain haemoglobin variants has been described. The data indicate that the most likely molecular basis for these common abnormal haemoglobins is a single base substitution in the alpha-chain termination codon. Because these variants are produced inefficiently they give rise to the clinical picture of alpha-thalassaemia. When these findings are taken together with recent work regarding the molecular basis for other forms of alpha-thalassaemia it is possible to build up a fairly complete picture of the molecular pathology of the alpha-thalassaemias.", "contents": "The alpha-chain-termination mutants and their relation to the alpha-thalassaemias. The structure, synthesis, genetic transmission, clinical associations and distribution of the elongated alpha-chain haemoglobin variants has been described. The data indicate that the most likely molecular basis for these common abnormal haemoglobins is a single base substitution in the alpha-chain termination codon. Because these variants are produced inefficiently they give rise to the clinical picture of alpha-thalassaemia. When these findings are taken together with recent work regarding the molecular basis for other forms of alpha-thalassaemia it is possible to build up a fairly complete picture of the molecular pathology of the alpha-thalassaemias."}
{"id": "PMID:240179", "title": "Correlation between plasma levels of prolactin and chlorpromazine in psychiatric patients.", "content": "Plasma levels of chlorpromazine (CPZ) and prolactin were measured repeatedly in 14 psychiatric patients throughout CPZ treatment.  Mean prolactin level was elevated in 11 subjects (all six women and five of eight men).  Mean plasma prolactin correlated significantly with mean plasma CPZ but not with the dose of the drug.  Only patients with mean plasma prolactin above 35 ng/ml developed Parkinsonian side-effects.", "contents": "Correlation between plasma levels of prolactin and chlorpromazine in psychiatric patients. Plasma levels of chlorpromazine (CPZ) and prolactin were measured repeatedly in 14 psychiatric patients throughout CPZ treatment.  Mean prolactin level was elevated in 11 subjects (all six women and five of eight men).  Mean plasma prolactin correlated significantly with mean plasma CPZ but not with the dose of the drug.  Only patients with mean plasma prolactin above 35 ng/ml developed Parkinsonian side-effects."}
{"id": "PMID:240180", "title": "Auditory signal detectability and facilitation of simple reaction time in psychiatric patients and non-patients.", "content": "Patients diagnosed on the basis of structured interviews as having affective psychoses were less sensitive in detecting the presence of a transient auditory signal than were schizophrenic patients or non-patients. Patients with affective psychoses also benefited more (their reaction time was more reduced) than the other two groups from the presence of a second auditory transient.", "contents": "Auditory signal detectability and facilitation of simple reaction time in psychiatric patients and non-patients. Patients diagnosed on the basis of structured interviews as having affective psychoses were less sensitive in detecting the presence of a transient auditory signal than were schizophrenic patients or non-patients. Patients with affective psychoses also benefited more (their reaction time was more reduced) than the other two groups from the presence of a second auditory transient."}
{"id": "PMID:240181", "title": "Dopaminergic mediation of the interoceptive cue produced by d-amphetamine in rats.", "content": "After rats were trained to differentiate between the effects of d-amphetamine and saline in a state-dependent task, pretreatment with the tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine, significantly decreased amphetamine discrimination. Pretreatment with the dopamine-beta-hydroxylase inhibitor, disulfiram, or with the tryptophan hydroxylase inhibitor, p-chloro-phenylalanine, was observed to have no effect on the rats' ability to discriminate d-amphetamine. Administration of haloperidol, a selective dopamine receptor blocker, completely abolished the amphetamine discrimination, whereas alpha- and beta-adrenergic receptor blockade had no effect. Apomorphine, a dopamine receptor stimulant, produced amphetamine-like responses and this was, likewise, abolished by pretreatment with haloperidol. These data suggest that dopaminergic systems mediate the interoceptive cue produced by d-amphetamine in rats, and these results are discussed in relation to possible dopamine mediation of amphetamine psychosis and paranoid schizophrenia.", "contents": "Dopaminergic mediation of the interoceptive cue produced by d-amphetamine in rats. After rats were trained to differentiate between the effects of d-amphetamine and saline in a state-dependent task, pretreatment with the tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine, significantly decreased amphetamine discrimination. Pretreatment with the dopamine-beta-hydroxylase inhibitor, disulfiram, or with the tryptophan hydroxylase inhibitor, p-chloro-phenylalanine, was observed to have no effect on the rats' ability to discriminate d-amphetamine. Administration of haloperidol, a selective dopamine receptor blocker, completely abolished the amphetamine discrimination, whereas alpha- and beta-adrenergic receptor blockade had no effect. Apomorphine, a dopamine receptor stimulant, produced amphetamine-like responses and this was, likewise, abolished by pretreatment with haloperidol. These data suggest that dopaminergic systems mediate the interoceptive cue produced by d-amphetamine in rats, and these results are discussed in relation to possible dopamine mediation of amphetamine psychosis and paranoid schizophrenia."}
{"id": "PMID:240182", "title": "Differential effects of heart rate modification training on college students, older males, and patients with ischemic heart disease.", "content": "Seventy male subjects participated in a six session study of feedback-mediated heart rate modification. Three groups of subjects were compared: (1) college students, (2) patients with ischemic heart disease, and (3) healthy males, age-matched to the patients. The groups did not differ in heart rate during rest or in response to a perceptual-motor tracking task. However, the college students produced significantly larger changes in cardiac rate than the other two groups when instructed to modify heart rate (speed or slow) and provided with exteroceptive feedback. The patients showed the poorest overall feedback performance. These differences between groups were greater for speeding than for the slowing task. Relationships were explored between feedback performance and resting heart and respiration rate, drug regime, and personality questionnaires. The results were consistent with the hypothesis that interdependence between psychological stimuli and cardiovascular events is reduced in heart disease.", "contents": "Differential effects of heart rate modification training on college students, older males, and patients with ischemic heart disease. Seventy male subjects participated in a six session study of feedback-mediated heart rate modification. Three groups of subjects were compared: (1) college students, (2) patients with ischemic heart disease, and (3) healthy males, age-matched to the patients. The groups did not differ in heart rate during rest or in response to a perceptual-motor tracking task. However, the college students produced significantly larger changes in cardiac rate than the other two groups when instructed to modify heart rate (speed or slow) and provided with exteroceptive feedback. The patients showed the poorest overall feedback performance. These differences between groups were greater for speeding than for the slowing task. Relationships were explored between feedback performance and resting heart and respiration rate, drug regime, and personality questionnaires. The results were consistent with the hypothesis that interdependence between psychological stimuli and cardiovascular events is reduced in heart disease."}
{"id": "PMID:240188", "title": "Work in progress. Occurence of phospholipase A1 and A2 in human decidua.", "content": "Phospholipase A2, an enzyme which may regulate the formation of polyunsaturated fatty acids utilized for prostaglandin synthesis, was found to have significant higher activity in decidual than in myometrial tissue. The major part of phospholipase A2 in the decidua had an acid pH optimum, which indicates that most of the enzyme is stored in the lysosomes of this tissue. These findings, together with previous observations, lend further support to the view that lysosomal phospholipase A2 released within decidual cells might be a trigger of abortion and parturition.", "contents": "Work in progress. Occurence of phospholipase A1 and A2 in human decidua. Phospholipase A2, an enzyme which may regulate the formation of polyunsaturated fatty acids utilized for prostaglandin synthesis, was found to have significant higher activity in decidual than in myometrial tissue. The major part of phospholipase A2 in the decidua had an acid pH optimum, which indicates that most of the enzyme is stored in the lysosomes of this tissue. These findings, together with previous observations, lend further support to the view that lysosomal phospholipase A2 released within decidual cells might be a trigger of abortion and parturition."}
{"id": "PMID:240189", "title": "Studies on closure of the ductus arteriosus. X. In vivo effect of prostaglandin.", "content": "The effect of prostaglandins F2alpha, E1 and of 7-oxa-13-prostynoic acid on the newborn rabbit ductus can be studied using the whole-body freezing technique. PGF2alpha and PGE1 were able to re-open the closing ductus arteriosus in adequately oxygenated animals. PGF2alpha administration was accompanied by a strong physical reaction in the rat but less in the rabbit. PGE1 had sedative effects in both animals. A prostaglandin antagonist, 7-oxa-13-prostynoic acid had no effect on normal ductal closure nor did it counteract the effects of PGF2alpha and PGE1. The role of prostaglandins in homeostasis during the fetal and newborn period may be to modify ductal tone.", "contents": "Studies on closure of the ductus arteriosus. X. In vivo effect of prostaglandin. The effect of prostaglandins F2alpha, E1 and of 7-oxa-13-prostynoic acid on the newborn rabbit ductus can be studied using the whole-body freezing technique. PGF2alpha and PGE1 were able to re-open the closing ductus arteriosus in adequately oxygenated animals. PGF2alpha administration was accompanied by a strong physical reaction in the rat but less in the rabbit. PGE1 had sedative effects in both animals. A prostaglandin antagonist, 7-oxa-13-prostynoic acid had no effect on normal ductal closure nor did it counteract the effects of PGF2alpha and PGE1. The role of prostaglandins in homeostasis during the fetal and newborn period may be to modify ductal tone."}
{"id": "PMID:240190", "title": "Prostaglandin synthetase activity from human rheumatoid synovial tissue and its inhibition by non-steroidal anti-inflammatory drugs.", "content": "1. Prostaglandin synthetase activity was found in a microsomal fraction from human rheumatoid synovia. 2. The microsomes produced PGE2 and a small amount of PGF2 when incubated with arachidonic acid. 3. The pH optimum of the enzyme from this source was similar to that found with microsomal preparations from rabbit renal medullae and bovine seminal vesicles. 4. The enzyme was inhibited in vitro by the non-steroidal anti-inflammatory drugs flurbiprofen, indomethacin and aspirin in the same rank order of potency as prostaglandin synthetase from other tissues.", "contents": "Prostaglandin synthetase activity from human rheumatoid synovial tissue and its inhibition by non-steroidal anti-inflammatory drugs. 1. Prostaglandin synthetase activity was found in a microsomal fraction from human rheumatoid synovia. 2. The microsomes produced PGE2 and a small amount of PGF2 when incubated with arachidonic acid. 3. The pH optimum of the enzyme from this source was similar to that found with microsomal preparations from rabbit renal medullae and bovine seminal vesicles. 4. The enzyme was inhibited in vitro by the non-steroidal anti-inflammatory drugs flurbiprofen, indomethacin and aspirin in the same rank order of potency as prostaglandin synthetase from other tissues."}
{"id": "PMID:240193", "title": "[Purification and properties of guinea pig liver ornithine transcarbamylase].", "content": "Ornithine transcarbamylase, the enzyme which catalyzes the formation of citrulline from ornithine and carbamoylphosphate, has been purified from guinea pig liver. By the procedure indicated in the present paper a 200 fold purification of the enzyme has been achieved. Using both the purified fraction and the crude extract, a parallel determination of some physicochemical properties has been carried out. The pH of maximal activity of OTC was 7.8 for both preparations. The maximal stability of the enzyme with respect of pH showed a plateau over the range of pH 7 to 9.5 in the purified fraction, whereas the crude extract exhibited a major stability which lay between pH and 10. Both OTC preparations showed similar behavior regarding thermal stability, the enzyme being still active at a 50 degrees C temperature. The values of the apparent Km's proved to be 4.4 mM for the substrate ornithine and 5 mM for carbamoylphosphate.", "contents": "[Purification and properties of guinea pig liver ornithine transcarbamylase]. Ornithine transcarbamylase, the enzyme which catalyzes the formation of citrulline from ornithine and carbamoylphosphate, has been purified from guinea pig liver. By the procedure indicated in the present paper a 200 fold purification of the enzyme has been achieved. Using both the purified fraction and the crude extract, a parallel determination of some physicochemical properties has been carried out. The pH of maximal activity of OTC was 7.8 for both preparations. The maximal stability of the enzyme with respect of pH showed a plateau over the range of pH 7 to 9.5 in the purified fraction, whereas the crude extract exhibited a major stability which lay between pH and 10. Both OTC preparations showed similar behavior regarding thermal stability, the enzyme being still active at a 50 degrees C temperature. The values of the apparent Km's proved to be 4.4 mM for the substrate ornithine and 5 mM for carbamoylphosphate."}
{"id": "PMID:240194", "title": "A comparison of some methods for determining oxygen dissociation curves of fish blood.", "content": "A brief description is given of four different methods for determining the oxygen dissociation curve of trout blood at pH 7.8 and 15 degrees C. A comparison of the results obtained indicates that the methods give similar results, especially when used by experienced workers. The relative advantages and disadvantages of the methods for determination of some O2-carrying parameters of fish blood are discussed.", "contents": "A comparison of some methods for determining oxygen dissociation curves of fish blood. A brief description is given of four different methods for determining the oxygen dissociation curve of trout blood at pH 7.8 and 15 degrees C. A comparison of the results obtained indicates that the methods give similar results, especially when used by experienced workers. The relative advantages and disadvantages of the methods for determination of some O2-carrying parameters of fish blood are discussed."}
{"id": "PMID:240199", "title": "[Physiopathology of hepatitis B virus infection].", "content": "Hepatitis B associated antigen (HB-Ag) may be observed in the serum in subjects either apparently healthy or exhibiting a number of disease symptoms. Its incidence among the Geneva voluntary blood donors is 0.48% with 54% exhibiting the surface antigen ad and 34% ay. While the HB-Ag positive blood donors appeared clinically healthy, minor pathology was found in the majority of them (thrombocytopenia, histological evidence of inflammatory foci, of persistent hepatitis and of chronic aggressive hepatitis). In 82 patients suffering from hepatitis B the same ad-ay type distribution of the HB-Ag has been found. In 11 out of 31 patients increased Clq binding suggests the presence of circulating complexes. Diminutions in the level of complement components also indicates participation of complement in the formation of immunocomplexes. In 2 out of 3 patients with Hb-Ag positive polyarteritis nodosa, the Clq binding test was also positive. The pathophysiologic implications of hepatitis B infection are discussed in connection with the authors and other findings. It appears that the main defense mechanism leading to elimination of the viruses within the hepatocytes lies in cell mediated immunity. Hepatitis would then represent the side reaction of this defense mechanism. Antibodies are probably useful in preventing the virus from entering the cell, but also in the course of the cell mediated defense mechanism (elimination of viral material liberated during the T-cell hepatocellular interaction). Immune complexes may be operative in certain extrahepatic manifestations such as arthralgia. Polyarteritis nodosa may result from local antibody interaction with antigen fixed within arterial walls.", "contents": "[Physiopathology of hepatitis B virus infection]. Hepatitis B associated antigen (HB-Ag) may be observed in the serum in subjects either apparently healthy or exhibiting a number of disease symptoms. Its incidence among the Geneva voluntary blood donors is 0.48% with 54% exhibiting the surface antigen ad and 34% ay. While the HB-Ag positive blood donors appeared clinically healthy, minor pathology was found in the majority of them (thrombocytopenia, histological evidence of inflammatory foci, of persistent hepatitis and of chronic aggressive hepatitis). In 82 patients suffering from hepatitis B the same ad-ay type distribution of the HB-Ag has been found. In 11 out of 31 patients increased Clq binding suggests the presence of circulating complexes. Diminutions in the level of complement components also indicates participation of complement in the formation of immunocomplexes. In 2 out of 3 patients with Hb-Ag positive polyarteritis nodosa, the Clq binding test was also positive. The pathophysiologic implications of hepatitis B infection are discussed in connection with the authors and other findings. It appears that the main defense mechanism leading to elimination of the viruses within the hepatocytes lies in cell mediated immunity. Hepatitis would then represent the side reaction of this defense mechanism. Antibodies are probably useful in preventing the virus from entering the cell, but also in the course of the cell mediated defense mechanism (elimination of viral material liberated during the T-cell hepatocellular interaction). Immune complexes may be operative in certain extrahepatic manifestations such as arthralgia. Polyarteritis nodosa may result from local antibody interaction with antigen fixed within arterial walls."}
{"id": "PMID:240201", "title": "[Acquired ulcero-mutilating acropathies in adults. Critical study of 150 personal cases].", "content": "The authors review critically a series of cases, followed up by the authors, of acrodynia and trophic ulcers occurring either in alcoholics (119 cases) or in diabetics (28 cases), who were also often alcoholic as well. The symptoms were similar in both groups. However, the poor nutrition was generally more market in the alcoholics. The trophic disorders were very similar, together with the sensory disorders. However, the deep sensitivity was less rarely involved in diabetics. Above all, the study of the rate of conduction of the motor nerve fibers showed axonal involvement in alcoholics and segmental demyelinisation in diabetics. The treatment was mainly dietary, together with proper hygiene and immobilisation of the foot.", "contents": "[Acquired ulcero-mutilating acropathies in adults. Critical study of 150 personal cases]. The authors review critically a series of cases, followed up by the authors, of acrodynia and trophic ulcers occurring either in alcoholics (119 cases) or in diabetics (28 cases), who were also often alcoholic as well. The symptoms were similar in both groups. However, the poor nutrition was generally more market in the alcoholics. The trophic disorders were very similar, together with the sensory disorders. However, the deep sensitivity was less rarely involved in diabetics. Above all, the study of the rate of conduction of the motor nerve fibers showed axonal involvement in alcoholics and segmental demyelinisation in diabetics. The treatment was mainly dietary, together with proper hygiene and immobilisation of the foot."}
{"id": "PMID:240203", "title": "Renal artery stenosis--then and now.", "content": "Diagnostic approaches evolve steadily. Selective renal arteriography and determination of renal vein renins have replaced differential clearances and translumbar aortography. The hydrated intravenous pyelogram remains helpful in assessing physiologic significance and complements both aortography and renin determinations. Except for young patients, medical treatment rather than surgical management usually is preferred.", "contents": "Renal artery stenosis--then and now. Diagnostic approaches evolve steadily. Selective renal arteriography and determination of renal vein renins have replaced differential clearances and translumbar aortography. The hydrated intravenous pyelogram remains helpful in assessing physiologic significance and complements both aortography and renin determinations. Except for young patients, medical treatment rather than surgical management usually is preferred."}
{"id": "PMID:240205", "title": "The use of lorazepam as a soporific and for premedication.", "content": "An open study, in which 48 patients scheduled for elective surgery received either 1,25 mg or 2,5 mg of lorazepam (orally) as a soporific the night before surgery and as premedication immediately prior to surgery, revealed that lorazepam produced a good night's rest and a desirable calm immediately prior to surgery. Vital signs remained stable throughout the operative procedure, and vomiting and other reactions were virtually absent.", "contents": "The use of lorazepam as a soporific and for premedication. An open study, in which 48 patients scheduled for elective surgery received either 1,25 mg or 2,5 mg of lorazepam (orally) as a soporific the night before surgery and as premedication immediately prior to surgery, revealed that lorazepam produced a good night's rest and a desirable calm immediately prior to surgery. Vital signs remained stable throughout the operative procedure, and vomiting and other reactions were virtually absent."}
{"id": "PMID:240206", "title": "Bicarbonate excretion in kwashiorkor.", "content": "Children with kwashiorkor have an impairment of bicarbonate excretion which may result in the inappropriate production of acid urine in the presence of systemic alkalosis. This defect has resolved after 2 weeks of treatment.", "contents": "Bicarbonate excretion in kwashiorkor. Children with kwashiorkor have an impairment of bicarbonate excretion which may result in the inappropriate production of acid urine in the presence of systemic alkalosis. This defect has resolved after 2 weeks of treatment."}
{"id": "PMID:240207", "title": "Hepatitis B (surface) antigen in mothers and their infants.", "content": "Hepatitis B (surface) antigen (HBSAg) was found in the serum of 8 out of 4 245 women attending the antenatal clinic of the Queen Victoria Maternity Hospital Seven (0, 16%) were asymptomatic carriers of the antigen, while the eigth suffered from polyarteritis nodosa. Seven of the 8 babies born to these mothers were followed-up over periods of up to 18 months, and 1 has become a chronic carrier of HBSAg. The antigen was not detected in the colostrum (breast milk) of the 6 positive mothers tested, but it was present in amniotic fluid, placenta and cord blood of some of the mother-infant couples. The possible routes of transmission of the hepatitis B virus from mother to baby are discussed in the light of these findings. No cases of acute virus B hepatitis occurred in the latter months of pregnancy nor in the puerperium, among 4 088 women delivered at the hospital during this period.", "contents": "Hepatitis B (surface) antigen in mothers and their infants. Hepatitis B (surface) antigen (HBSAg) was found in the serum of 8 out of 4 245 women attending the antenatal clinic of the Queen Victoria Maternity Hospital Seven (0, 16%) were asymptomatic carriers of the antigen, while the eigth suffered from polyarteritis nodosa. Seven of the 8 babies born to these mothers were followed-up over periods of up to 18 months, and 1 has become a chronic carrier of HBSAg. The antigen was not detected in the colostrum (breast milk) of the 6 positive mothers tested, but it was present in amniotic fluid, placenta and cord blood of some of the mother-infant couples. The possible routes of transmission of the hepatitis B virus from mother to baby are discussed in the light of these findings. No cases of acute virus B hepatitis occurred in the latter months of pregnancy nor in the puerperium, among 4 088 women delivered at the hospital during this period."}
{"id": "PMID:240208", "title": "Resistance of the Candida albicans filamentous cycle to environmental change.", "content": "The filamentous growth cycle in C. albicans was resistant to changes in environment brought about either by the serial transfer of growing cells to fresh nutrients or by sudden changes of temperature after the first h of growth. In further experiments older culture filtrates, exhausted of their ability to induce mycelial growth, were reactivated by addition of fresh nutrients or water. The data provided evidence against the existence of both a mycelial stimulatory and inhibitory compound in the growth medium. It is concluded that although the environment initially dictates what proportion of blastospores are committed to filamentation it has no further effect on the process.", "contents": "Resistance of the Candida albicans filamentous cycle to environmental change. The filamentous growth cycle in C. albicans was resistant to changes in environment brought about either by the serial transfer of growing cells to fresh nutrients or by sudden changes of temperature after the first h of growth. In further experiments older culture filtrates, exhausted of their ability to induce mycelial growth, were reactivated by addition of fresh nutrients or water. The data provided evidence against the existence of both a mycelial stimulatory and inhibitory compound in the growth medium. It is concluded that although the environment initially dictates what proportion of blastospores are committed to filamentation it has no further effect on the process."}
{"id": "PMID:240209", "title": "Operative technique in myocardial revascularization.", "content": "This article necessarily deals exclusively with vein and artery bypass grafts. The venous autograft remains the most versatile operation and data thus far compiled verify its reliability. We advocate normotensive, normothermic perfusion and recommend the interrupted suture technique for most anastomoses. Our guidelines for IMA grafting indicate its applicability for most anterolateral wall vessels, except for unstable emergency patients and those with a large left ventricular mass. We emphasize that the technical details are far more important than the steps involved in coronary artery operations. The operative techniques described and discussed herein are deceptively simple, and direct coronary artery surgery often appears uncomplicated to the inexperienced observerer. However, one should not attempt myocardial revascularization without the benefit of high quality cinecoronary arteriograms. An organized and experienced operative team is mandatory and, above all, the procedure itself must not be an endurance contest between surgeon and patient. Expeditious revascularization produces less morbidity and better overall results.", "contents": "Operative technique in myocardial revascularization. This article necessarily deals exclusively with vein and artery bypass grafts. The venous autograft remains the most versatile operation and data thus far compiled verify its reliability. We advocate normotensive, normothermic perfusion and recommend the interrupted suture technique for most anastomoses. Our guidelines for IMA grafting indicate its applicability for most anterolateral wall vessels, except for unstable emergency patients and those with a large left ventricular mass. We emphasize that the technical details are far more important than the steps involved in coronary artery operations. The operative techniques described and discussed herein are deceptively simple, and direct coronary artery surgery often appears uncomplicated to the inexperienced observerer. However, one should not attempt myocardial revascularization without the benefit of high quality cinecoronary arteriograms. An organized and experienced operative team is mandatory and, above all, the procedure itself must not be an endurance contest between surgeon and patient. Expeditious revascularization produces less morbidity and better overall results."}
{"id": "PMID:240211", "title": "Effects and distribution of acute fat embolism in spontaneously breathing dogs using radioactive carbon triolein.", "content": "The acute effects of a triolein infusion in dogs were secondary to the mechanical effects of this neutral fat which was distributed in the pulmonary and systemic vascular tree of all organs without inflammatory change. Hypoxia developed immediately and became progressively worse as the infusion was continued. Pulmonary hypertension developed during the fat infusion without pneumonia, congestive heart failure or pulmonary edema. There was a slow leak of 14C triolein into the systemic circulation rather than a rapid shower, and this radioactive fat was recirculated between the pulmonary and systemic vasculature. Seventy-six per cent of the 14C triolein was retained in the lungs. Terminally, the dogs had a respiratory arrest without cardiac decompensation, cardiac arrest or pulmonary edema; cerebral fat embolism in addition to severe hypoxia appears to be the cause.", "contents": "Effects and distribution of acute fat embolism in spontaneously breathing dogs using radioactive carbon triolein. The acute effects of a triolein infusion in dogs were secondary to the mechanical effects of this neutral fat which was distributed in the pulmonary and systemic vascular tree of all organs without inflammatory change. Hypoxia developed immediately and became progressively worse as the infusion was continued. Pulmonary hypertension developed during the fat infusion without pneumonia, congestive heart failure or pulmonary edema. There was a slow leak of 14C triolein into the systemic circulation rather than a rapid shower, and this radioactive fat was recirculated between the pulmonary and systemic vasculature. Seventy-six per cent of the 14C triolein was retained in the lungs. Terminally, the dogs had a respiratory arrest without cardiac decompensation, cardiac arrest or pulmonary edema; cerebral fat embolism in addition to severe hypoxia appears to be the cause."}
{"id": "PMID:240213", "title": "Cryptorchism and related defects in dogs: epidemiologic comparisons with man.", "content": "In a study of 1266 dogs with cryptorchism from a large clinic/hospital series 8 breeds were found to be at excess risk of the defect and 3 breeds at significantly low risk. Review of the medical histories revealed that hip dysplasia, patellar dislocation, defects of the penis and prepuce, and umbilical hernia were excessively associated with cryptorchism. Testicular tumors were diagnosed 10.9 times more commonly among cryptorchid dogs. The epidemiologic features of canine cryptorchism were compared with those in man. Cryptorchid dogs could be used as models for etiologic research.", "contents": "Cryptorchism and related defects in dogs: epidemiologic comparisons with man. In a study of 1266 dogs with cryptorchism from a large clinic/hospital series 8 breeds were found to be at excess risk of the defect and 3 breeds at significantly low risk. Review of the medical histories revealed that hip dysplasia, patellar dislocation, defects of the penis and prepuce, and umbilical hernia were excessively associated with cryptorchism. Testicular tumors were diagnosed 10.9 times more commonly among cryptorchid dogs. The epidemiologic features of canine cryptorchism were compared with those in man. Cryptorchid dogs could be used as models for etiologic research."}
{"id": "PMID:240214", "title": "Physiological effects of hypoxia and trypan blue in 17-day chick embryos.", "content": "Seventeen-day chick embryos were divided into 5 groups and treated as follows: (1) untreated, (2) yolk-sac injected with 0.1 ml of saturated trypan blue solution solution in sterile saline, (3) saline, (4) hypoxia, i.e., 10.5% oxygen, and (5) hypoxia plus trypan blue. After 5 h  hypoxia-treated embryos had an increased mortality rate, severe hypoglycemia, reduced blood pH, elevated plasma potassium, and reduced CO2 content. Trypan blue treatment induced few deaths and few physiological imbalances. Hypoxia plus trypan blue was without synergistic effects and had effects that did not differ significantly from hypoxia alone. This lack of response of 17-day chick embryos to high doses of trypan blue may be related to a marked decline in oxygen consumption by the yolk at this age.", "contents": "Physiological effects of hypoxia and trypan blue in 17-day chick embryos. Seventeen-day chick embryos were divided into 5 groups and treated as follows: (1) untreated, (2) yolk-sac injected with 0.1 ml of saturated trypan blue solution solution in sterile saline, (3) saline, (4) hypoxia, i.e., 10.5% oxygen, and (5) hypoxia plus trypan blue. After 5 h  hypoxia-treated embryos had an increased mortality rate, severe hypoglycemia, reduced blood pH, elevated plasma potassium, and reduced CO2 content. Trypan blue treatment induced few deaths and few physiological imbalances. Hypoxia plus trypan blue was without synergistic effects and had effects that did not differ significantly from hypoxia alone. This lack of response of 17-day chick embryos to high doses of trypan blue may be related to a marked decline in oxygen consumption by the yolk at this age."}
{"id": "PMID:240220", "title": "[The protein distribution in  the postischemic edema of dogs in reference to pathogenesis (author's transl)].", "content": "A postischemic edema in hind limbs of dogs occurred after a 5 hours tourniquet ischemia. The protein distribution of edematous liquid, serum and lymph has been investigated by immunoelectrophoretic analysis. Using different identification reactions it could be demonstrated, that edematous liquid only differs from serum because of additional appearance of fibrinogen, so corresponding qualitatively and in so far estimated quantitatively to serum plasma. In connection with the osmotic pressure factors and postischemic hyperemia, as they have been demonstrated up to now, the severe changes of permeability seem to be a main factor in pathogenesis of postischemic edemas.", "contents": "[The protein distribution in  the postischemic edema of dogs in reference to pathogenesis (author's transl)]. A postischemic edema in hind limbs of dogs occurred after a 5 hours tourniquet ischemia. The protein distribution of edematous liquid, serum and lymph has been investigated by immunoelectrophoretic analysis. Using different identification reactions it could be demonstrated, that edematous liquid only differs from serum because of additional appearance of fibrinogen, so corresponding qualitatively and in so far estimated quantitatively to serum plasma. In connection with the osmotic pressure factors and postischemic hyperemia, as they have been demonstrated up to now, the severe changes of permeability seem to be a main factor in pathogenesis of postischemic edemas."}
{"id": "PMID:240221", "title": "[Comparison of tolerance to ischemia in human and animal myocardium during various forms of induced cardiac arrest (author's transl)].", "content": "In a total of 16 patients the tissue pH was determined on myocardium both during surgery and on isolated samples. Cardiac arrest was induced by hypothermal infusion cardioplegia and external cooling. In the isolated human myocardium section pH values were continuously determined at 15 degrees C. Parallel to these measurements samples were taken for electron microscopic examinations. In this way the pH limit under which the human myocardium cannot be revived could be visualized by additional morphologic examination. These results and those from the intrasurgical measurements with a fixed heart muscle surface probe were compared with each other and with results from animal experiments.", "contents": "[Comparison of tolerance to ischemia in human and animal myocardium during various forms of induced cardiac arrest (author's transl)]. In a total of 16 patients the tissue pH was determined on myocardium both during surgery and on isolated samples. Cardiac arrest was induced by hypothermal infusion cardioplegia and external cooling. In the isolated human myocardium section pH values were continuously determined at 15 degrees C. Parallel to these measurements samples were taken for electron microscopic examinations. In this way the pH limit under which the human myocardium cannot be revived could be visualized by additional morphologic examination. These results and those from the intrasurgical measurements with a fixed heart muscle surface probe were compared with each other and with results from animal experiments."}
{"id": "PMID:240224", "title": "Modification of hybrid responsiveness in the local graft-versus-host reaction by injection of parental lymphocytes.", "content": "The local graft-versus-host reaction in F1 hybrid rats, assayed by popliteal lymph node enlargement, is specifically depressed by pretreating the host with parental lymphocytes. The conditions for demonstrating specific depression are injection of a small dose of parental lymphocytes and assay 7 days later. Pretreatment with cells from thymus and bone marrow is ineffective, as is pretreatment with purified B lymphocytes. The structures which stimulate the suppressed response of F1 hybrids are not present on parental B lymphocytes.", "contents": "Modification of hybrid responsiveness in the local graft-versus-host reaction by injection of parental lymphocytes. The local graft-versus-host reaction in F1 hybrid rats, assayed by popliteal lymph node enlargement, is specifically depressed by pretreating the host with parental lymphocytes. The conditions for demonstrating specific depression are injection of a small dose of parental lymphocytes and assay 7 days later. Pretreatment with cells from thymus and bone marrow is ineffective, as is pretreatment with purified B lymphocytes. The structures which stimulate the suppressed response of F1 hybrids are not present on parental B lymphocytes."}
{"id": "PMID:240233", "title": "[Cryopreservation of hemopoietic stem cells (author's transl)].", "content": "The CFU-S potential of mouse bone marrow, the transplantation capacity of autologous and allogeneic monkey bone marrow and the CFU-C potential of human bone marrow can be cryopreserved without loss of viability. It is critical for an optimal stem cell recovery to avoid an osmotic shock after thawing. The intracellular cryoprotectives glycerol and DMSO which provide a high osmotic pressure should be removed from the thawed cells by a slow stepwise dilution procedure.", "contents": "[Cryopreservation of hemopoietic stem cells (author's transl)]. The CFU-S potential of mouse bone marrow, the transplantation capacity of autologous and allogeneic monkey bone marrow and the CFU-C potential of human bone marrow can be cryopreserved without loss of viability. It is critical for an optimal stem cell recovery to avoid an osmotic shock after thawing. The intracellular cryoprotectives glycerol and DMSO which provide a high osmotic pressure should be removed from the thawed cells by a slow stepwise dilution procedure."}
{"id": "PMID:240234", "title": "Induction of neurogenic tumors by nitrosotrialkylureas in rats.", "content": "Four nitrosotrialkylureas were each fed to groups of 15 male and 15 female Sprague-Dawley rats for 50 weeks in drinking water at the same molar concentration. Tumors of nervous origin arose after treatment with nitrosotrimethylurea (3/30), notrosotriethylurea (7/30), nitrosomethyldiethylurea (23/30), and nitrosoethyldimethylurea (8/30). A comparison of the relative stabilities of the four nitrosoureas in aqueous solution at various pH's showed no correlation with the tumorigenicities of the compounds.", "contents": "Induction of neurogenic tumors by nitrosotrialkylureas in rats. Four nitrosotrialkylureas were each fed to groups of 15 male and 15 female Sprague-Dawley rats for 50 weeks in drinking water at the same molar concentration. Tumors of nervous origin arose after treatment with nitrosotrimethylurea (3/30), notrosotriethylurea (7/30), nitrosomethyldiethylurea (23/30), and nitrosoethyldimethylurea (8/30). A comparison of the relative stabilities of the four nitrosoureas in aqueous solution at various pH's showed no correlation with the tumorigenicities of the compounds."}
{"id": "PMID:240235", "title": "[Oxygen transport in the blood of children with congenital heart defects].", "content": "In 55 children with congenital heart defects (aged 6 months and older), hematocrit, hemoglobin concentration, acid-base status, oxygen pressure, oxygen saturation, and 2,3-DPG content of erythrocytes were determined in blood taken from the vena cava superior. The data were correlated with each other as well as with parameters obtained during cardiac catheterization. Whereas an increased hematocrit was seen only at a difference in arteriovenous oxygen saturation of more than 30%, or a central venous saturation below 65%, a close correlation between 2,3-DPG concentration in erythrocytes and these parameters was obtained already in the normal range (r = 0.79, and r = 0.78, respectively). A relatively close correlation was also found between 2,3-DPG concentration and half-maximal oxygen saturation pressure (T50 value; r equals 0.73), and the T50 values and the central venous oxygen saturation (r equals 0.61), respectively. Because of the shift to the right of the O2-binding curve the functional oxygen transport capacity was increased by an average 15% in children with acyanotic heart defects (mean T50 value of 31.6 mm Hg), and by 40% in children with cyanotic heart defects (mean T50 value of 34.6 mm Hg), as compared to healthy children (mean T50 value of 28.1 mm Hg). A marked influence on the position of the O2-binding curve and hence on oxygen release of the blood in the periphery is therefore exerted by the 2,3-DPG concentration, whose effect was about twice that of the Bohr effect in the pH range measured.", "contents": "[Oxygen transport in the blood of children with congenital heart defects]. In 55 children with congenital heart defects (aged 6 months and older), hematocrit, hemoglobin concentration, acid-base status, oxygen pressure, oxygen saturation, and 2,3-DPG content of erythrocytes were determined in blood taken from the vena cava superior. The data were correlated with each other as well as with parameters obtained during cardiac catheterization. Whereas an increased hematocrit was seen only at a difference in arteriovenous oxygen saturation of more than 30%, or a central venous saturation below 65%, a close correlation between 2,3-DPG concentration in erythrocytes and these parameters was obtained already in the normal range (r = 0.79, and r = 0.78, respectively). A relatively close correlation was also found between 2,3-DPG concentration and half-maximal oxygen saturation pressure (T50 value; r equals 0.73), and the T50 values and the central venous oxygen saturation (r equals 0.61), respectively. Because of the shift to the right of the O2-binding curve the functional oxygen transport capacity was increased by an average 15% in children with acyanotic heart defects (mean T50 value of 31.6 mm Hg), and by 40% in children with cyanotic heart defects (mean T50 value of 34.6 mm Hg), as compared to healthy children (mean T50 value of 28.1 mm Hg). A marked influence on the position of the O2-binding curve and hence on oxygen release of the blood in the periphery is therefore exerted by the 2,3-DPG concentration, whose effect was about twice that of the Bohr effect in the pH range measured."}
{"id": "PMID:240231", "title": "[Identification of a group A arbovirus isolated in the Far East].", "content": "Strains Nos. 296 and 260 isolated from Aedes vexans and Culex pipiens mosquitoes in the USSR Far East in 1971 and 1973, respectively, were identified. The size of the viruses was found to be about 50 nm. Both strains were pathogenic for 2--3-day-old and 3--4-week-old mice by the intracerebral, subcutaneous and intraperitoneal routes, agglutinated goose red blood cells at the optimal pH 6.0. The strains were identical to each other and by their antigenic structure were classified as Semliki Forest virus.", "contents": "[Identification of a group A arbovirus isolated in the Far East]. Strains Nos. 296 and 260 isolated from Aedes vexans and Culex pipiens mosquitoes in the USSR Far East in 1971 and 1973, respectively, were identified. The size of the viruses was found to be about 50 nm. Both strains were pathogenic for 2--3-day-old and 3--4-week-old mice by the intracerebral, subcutaneous and intraperitoneal routes, agglutinated goose red blood cells at the optimal pH 6.0. The strains were identical to each other and by their antigenic structure were classified as Semliki Forest virus."}
{"id": "PMID:240236", "title": "[Effect of potassium-magnesium aspartate on hemodynamics and myocardial metabolism of coronary disease patient during beta receptor stimulation].", "content": "2 series of patients with angiographically proven coronary artery disease were studied under the influence of an infusion of a beta-receptor stimulating drug (heptaminole) and of kalium-magnesium-aspartate (KMA) in high (series: I: 1000 mg of heptaminole in 25 min) and low doses (series II: 200 mg of heptaminole in 25 min) of beta-receptor stimulation. The results confirm the finding that high dose beta-receptor stimulation in patients with severe coronary artery disease results in failure of the contractile mechanism of the heart with the beta-receptor angina. However, administration of KMA simultaneously with the beta-receptor stimulator seems to be able to prevent the expected decrease of lactate extraction and results in no change in lactate AVD in series I and even in an 11% increase in lactate AVD in series II. Experimental data concerning the biochemical effects of KMA suggest that its ability to provide adequate amounts of oxaloacetone and hence to improve the function of the bricarbonic acid cycle seems to be of special importance. For this action to become relevant in coronary artery disease a situation would have to be postulated, in which an additional limiting factor of oxydative metabolism would be an inadequate supply of Krebs-cycle intermediates.", "contents": "[Effect of potassium-magnesium aspartate on hemodynamics and myocardial metabolism of coronary disease patient during beta receptor stimulation]. 2 series of patients with angiographically proven coronary artery disease were studied under the influence of an infusion of a beta-receptor stimulating drug (heptaminole) and of kalium-magnesium-aspartate (KMA) in high (series: I: 1000 mg of heptaminole in 25 min) and low doses (series II: 200 mg of heptaminole in 25 min) of beta-receptor stimulation. The results confirm the finding that high dose beta-receptor stimulation in patients with severe coronary artery disease results in failure of the contractile mechanism of the heart with the beta-receptor angina. However, administration of KMA simultaneously with the beta-receptor stimulator seems to be able to prevent the expected decrease of lactate extraction and results in no change in lactate AVD in series I and even in an 11% increase in lactate AVD in series II. Experimental data concerning the biochemical effects of KMA suggest that its ability to provide adequate amounts of oxaloacetone and hence to improve the function of the bricarbonic acid cycle seems to be of special importance. For this action to become relevant in coronary artery disease a situation would have to be postulated, in which an additional limiting factor of oxydative metabolism would be an inadequate supply of Krebs-cycle intermediates."}
{"id": "PMID:240237", "title": "The effect of an antiserum to plastocyanin on various chloroplast preparations.", "content": "A monospecific antiserum to tobacco plastocyanin agglutinates stroma-free swellable chloroplasts from wild type tobacco, (Nicotiana tobacum var. John William's Broadleaf) from the tobacco aurea mutant Su/su2, (Nicotiana tabacum var. Su/su2) from Antirrhinum majus and spinach (Spinacia oleracea). In this condition the antiserum inhibits linear photosynthetic electron flow in tobacco and spinach chloroplasts. This inhibition of electron transport as well as the agglutination are not observed if the chloroplasts have been sonicated prior to antiserum addition. This is due to the fact that plastocyanin is removed by ultasonication. The antiserum stimulates a number of photophosphorylation reactions in tobacco chloroplasts. This stimulation is always larger in the aurea mutant chloroplasts from yellow leaf patches of a variegated tobacco mutant (N. tabacum, var. NC 95) than in the green type chloroplasts. The stimulation appears to be a consequence of the inhibition of linear electron transport. The antiserum does not affect PMS-mediated cyclic photophosphorylation in tobacco chloroplasts from the wild type whereas the reaction appears stimulated in the tobacco mutant chloroplasts. However, menadione-mediated cyclic photophosphorylation is inhibited upon addition of the antiserum. The same is true for noncyclic photophosphorylation coupled to electron transport in the aerobic system diaminodurene/ascorbate leads to methylviologen in the presence of N-tetraphenyl-p-phenylenediamine in spinach chlorplasts. If the lamellar system of Antirrhinum and spinach has lost is swellability neither agglutination nor inhibition of electron transport is observed. However, also in this state antibodies to plastocyanin are specifically adsorbed onto the surface to the thylakoid membrane. This state which is characterized by a morphologically well preserved lamellar system is realized in chloroplast preparations from Antirrhinum and spinach and is termed stroma-freed chloroplasts. In both states of the molecular structure of the thylakoid membrane, plastocyanin is located in the outer surface of the thylakoid. However, it cannot be excluded that functioning plastocyanin is also located in the interior of the thylakoid membrane.", "contents": "The effect of an antiserum to plastocyanin on various chloroplast preparations. A monospecific antiserum to tobacco plastocyanin agglutinates stroma-free swellable chloroplasts from wild type tobacco, (Nicotiana tobacum var. John William's Broadleaf) from the tobacco aurea mutant Su/su2, (Nicotiana tabacum var. Su/su2) from Antirrhinum majus and spinach (Spinacia oleracea). In this condition the antiserum inhibits linear photosynthetic electron flow in tobacco and spinach chloroplasts. This inhibition of electron transport as well as the agglutination are not observed if the chloroplasts have been sonicated prior to antiserum addition. This is due to the fact that plastocyanin is removed by ultasonication. The antiserum stimulates a number of photophosphorylation reactions in tobacco chloroplasts. This stimulation is always larger in the aurea mutant chloroplasts from yellow leaf patches of a variegated tobacco mutant (N. tabacum, var. NC 95) than in the green type chloroplasts. The stimulation appears to be a consequence of the inhibition of linear electron transport. The antiserum does not affect PMS-mediated cyclic photophosphorylation in tobacco chloroplasts from the wild type whereas the reaction appears stimulated in the tobacco mutant chloroplasts. However, menadione-mediated cyclic photophosphorylation is inhibited upon addition of the antiserum. The same is true for noncyclic photophosphorylation coupled to electron transport in the aerobic system diaminodurene/ascorbate leads to methylviologen in the presence of N-tetraphenyl-p-phenylenediamine in spinach chlorplasts. If the lamellar system of Antirrhinum and spinach has lost is swellability neither agglutination nor inhibition of electron transport is observed. However, also in this state antibodies to plastocyanin are specifically adsorbed onto the surface to the thylakoid membrane. This state which is characterized by a morphologically well preserved lamellar system is realized in chloroplast preparations from Antirrhinum and spinach and is termed stroma-freed chloroplasts. In both states of the molecular structure of the thylakoid membrane, plastocyanin is located in the outer surface of the thylakoid. However, it cannot be excluded that functioning plastocyanin is also located in the interior of the thylakoid membrane."}
{"id": "PMID:240238", "title": "[The importance of the substrate for the induction of tyrosine-alpha-ketoglutarate-transaminase in RLC-cells (author's transl)].", "content": "1. Dexamethasone phosphate causes approximately a threefold increase of the tyrosine-alpha-ketoglutarate transaminase in the culture of RLC cells. 2. The induction of the enzyme depends on the presence of L-tyrosine. Omission of L-leucine or L-tryptophan, respectively, has no effect. 3. Omission of L-tyrosine influences the activity of the lactate dehydrogenase and malate dehydrogenase not at all and that of the glucose-6-phosphate-dehydrogenase only to a small extent. 4. In the absense of L-tyrosine an superinduction takes also place by actinomycin.", "contents": "[The importance of the substrate for the induction of tyrosine-alpha-ketoglutarate-transaminase in RLC-cells (author's transl)]. 1. Dexamethasone phosphate causes approximately a threefold increase of the tyrosine-alpha-ketoglutarate transaminase in the culture of RLC cells. 2. The induction of the enzyme depends on the presence of L-tyrosine. Omission of L-leucine or L-tryptophan, respectively, has no effect. 3. Omission of L-tyrosine influences the activity of the lactate dehydrogenase and malate dehydrogenase not at all and that of the glucose-6-phosphate-dehydrogenase only to a small extent. 4. In the absense of L-tyrosine an superinduction takes also place by actinomycin."}
{"id": "PMID:240243", "title": "[Investigations of the influence of pH on the oxidative degradation of glucose by E. coli (biochemical glucose demand) (author's transl)].", "content": "The oxidative degradation of glucose by E. coli was studied in the Warburg manometer. The pH of the medium was established in these studies at values between 5.5 and 8.0. Analysis of the reaction kinetics by plotting time/consumption curves shows that three consecutive reactions can be distinguished as the substrate is eliminated from the medium: An adaptation phase which is generally relatively brief is followed by two reactions, of which the first proceeds more rapidly or more slowly than reaction 3, depending on pH. The important feature in reactions 1 and 2 is that the oxygen demand is evidently independent of the initial concentration of substrate. In spite of these differences, if the reaction is regarded as a whole, there are no relations involving significant dependence on pH of medium. Neither the substrate-specific biochemical oxygen demand nor the reaction time necessary for catabolism show statistically significant dependence within the range of pH examined. It can be assumed therefore that E. coli possesses a regulation mechanism which compensates for unfavourable environmental conditions. The division of substrate catabolism into constituent reactions, combined with a change in concentration of pacemaker enzyme and a \"competitive inhibition\" may be of significance in this regulations.", "contents": "[Investigations of the influence of pH on the oxidative degradation of glucose by E. coli (biochemical glucose demand) (author's transl)]. The oxidative degradation of glucose by E. coli was studied in the Warburg manometer. The pH of the medium was established in these studies at values between 5.5 and 8.0. Analysis of the reaction kinetics by plotting time/consumption curves shows that three consecutive reactions can be distinguished as the substrate is eliminated from the medium: An adaptation phase which is generally relatively brief is followed by two reactions, of which the first proceeds more rapidly or more slowly than reaction 3, depending on pH. The important feature in reactions 1 and 2 is that the oxygen demand is evidently independent of the initial concentration of substrate. In spite of these differences, if the reaction is regarded as a whole, there are no relations involving significant dependence on pH of medium. Neither the substrate-specific biochemical oxygen demand nor the reaction time necessary for catabolism show statistically significant dependence within the range of pH examined. It can be assumed therefore that E. coli possesses a regulation mechanism which compensates for unfavourable environmental conditions. The division of substrate catabolism into constituent reactions, combined with a change in concentration of pacemaker enzyme and a \"competitive inhibition\" may be of significance in this regulations."}
{"id": "PMID:240245", "title": "Acid-base relationship between mother and fetus in gestosis (pre-eclampsia) and in pregnant women with a labile blood pressure.", "content": "Simultaneous blood microsamples were taken from the maternal ear and uterine cervix and the fetus of healthy pregnant women, those with labile hypertension, and those with severe gestosis (pre-eclampsia). The po2, pH, BE and pco2 were studied. The fetuses showed no signs of asphyxia. The differences in BE values between the women withe gestosis and their fetuses were significantly greater than in the cases of healthy pregnancy. No differences were seen between healthy and gestotic gravida groups in po2, pH and pco2 values. This favours the opinion that in gestosis of the mother the fetus has a tendency to metabolic acidosis, which apparently places it in a poorer position than the fetuses of healthy mothers, should acute asphyxia occur. At the time of study the po2 of the fetuses of gravidas with a labile blood pressure was lower than that of fetuses of healthy gravidas.", "contents": "Acid-base relationship between mother and fetus in gestosis (pre-eclampsia) and in pregnant women with a labile blood pressure. Simultaneous blood microsamples were taken from the maternal ear and uterine cervix and the fetus of healthy pregnant women, those with labile hypertension, and those with severe gestosis (pre-eclampsia). The po2, pH, BE and pco2 were studied. The fetuses showed no signs of asphyxia. The differences in BE values between the women withe gestosis and their fetuses were significantly greater than in the cases of healthy pregnancy. No differences were seen between healthy and gestotic gravida groups in po2, pH and pco2 values. This favours the opinion that in gestosis of the mother the fetus has a tendency to metabolic acidosis, which apparently places it in a poorer position than the fetuses of healthy mothers, should acute asphyxia occur. At the time of study the po2 of the fetuses of gravidas with a labile blood pressure was lower than that of fetuses of healthy gravidas."}
{"id": "PMID:240250", "title": "Respiration and acid-base balance of blood after diffuse experimental brain injury.", "content": "Diffuse brain injury in rabbits was caused by injecting olive oil and saline into one internal carotid artery. In this report, the fourth of a series, the effects of this experimental brain injury on respiration and acid-base balance of blood are analyzed. The animals that withstood the injury best were those that had a lower pre-traumatic pCO2; the animals that suffered a rise in intracranial pressure and succumbed to the injury quickly did so in spite of pronounced hyperventilation after the injury. Arterial pCO2 immediately before the injury was the only significant prognostic factor in this analysis. Respiratory rate only dropped immediately before respiratory arrest and death. The findings concerning pCO2 tally with results after experimental ligation of a cerebral artery, but less so with results after other types of experimental brain injury. This emphasizes again that conclusions drawn from one type of brain injury must not be extrapolated to other types.", "contents": "Respiration and acid-base balance of blood after diffuse experimental brain injury. Diffuse brain injury in rabbits was caused by injecting olive oil and saline into one internal carotid artery. In this report, the fourth of a series, the effects of this experimental brain injury on respiration and acid-base balance of blood are analyzed. The animals that withstood the injury best were those that had a lower pre-traumatic pCO2; the animals that suffered a rise in intracranial pressure and succumbed to the injury quickly did so in spite of pronounced hyperventilation after the injury. Arterial pCO2 immediately before the injury was the only significant prognostic factor in this analysis. Respiratory rate only dropped immediately before respiratory arrest and death. The findings concerning pCO2 tally with results after experimental ligation of a cerebral artery, but less so with results after other types of experimental brain injury. This emphasizes again that conclusions drawn from one type of brain injury must not be extrapolated to other types."}
{"id": "PMID:240252", "title": "Sympatho-adrenal development in perinatally addicted rats.", "content": "Chronic morphine administration in adult rats results in neurogenic secretion of adrenal catecholamines and compensatory increases in basal catecholamine levels, in activities of catecholamine biosynthetic enzymes and in the number of storage vesicles in the tissue. Perinatally addicted developing rats demonstrated changes completely different from those seen in adults; catecholamine levels and dopamine beta-hydroxylase activity were reduced compared to controlscsnnofinduction of tyrosine hydroxylase was observed. The time course of adrenomedullary maturation was delayed throuth the first 10-20 days of age, with reduced numbers of storage vesicles and larger proportions of partially filled vesicles. On exposure to morphine, continued until weaning, perinatally addicted rats did not display any of the changes in catecholamine synthesis or uptake seen in adult rats. The differences between adults and developing rats can be partly explained by the absence of functional innervation of the neonatal adrenal medulla.", "contents": "Sympatho-adrenal development in perinatally addicted rats. Chronic morphine administration in adult rats results in neurogenic secretion of adrenal catecholamines and compensatory increases in basal catecholamine levels, in activities of catecholamine biosynthetic enzymes and in the number of storage vesicles in the tissue. Perinatally addicted developing rats demonstrated changes completely different from those seen in adults; catecholamine levels and dopamine beta-hydroxylase activity were reduced compared to controlscsnnofinduction of tyrosine hydroxylase was observed. The time course of adrenomedullary maturation was delayed throuth the first 10-20 days of age, with reduced numbers of storage vesicles and larger proportions of partially filled vesicles. On exposure to morphine, continued until weaning, perinatally addicted rats did not display any of the changes in catecholamine synthesis or uptake seen in adult rats. The differences between adults and developing rats can be partly explained by the absence of functional innervation of the neonatal adrenal medulla."}
{"id": "PMID:240257", "title": "Pathogen transmission in relation to feeding and digestion by haematophagous Arthropods.", "content": "The blood feeding habit, especially among opportunist feeders such as tabanids and Stomoxys is known to result in transmission of diseases for which the vectors are not the obligate or alternate hosts. Thus, mechanical transmission of trypanosomes such as T. vivax can occur in cattle herds outside tsetse fly areas where tabanids are actively feeding. In the case of Yaws, mechanical transmission of the spirochaetes by eye flies (Hippelates pallipes) in the West Indies is thought to be most likely. The spirochaetes remain motile in the pharynx and oesophageal diverticula for several hours but are apparently immobilised in the midgut (Kumm & Turner, 1936). There is apparently no development ofspirochaetes in the fly. They have been shown to pass through houseflies, but in mechanical transmission, biochemical transformation or adaptation of the pathogen is not implied. Virus transmission is common among arthropods and transovarial transmission to succeeding generations is frequent in mites and ticks. Although Yellow Fever virus is not transovarially transmitted by its vector Aedes aegypti, the mosquito only becomes infective some time after ingesting an infected blood meal (Chandler, 1955). Thus, metabolic or biochemical changes or adaptations in the virus or in the vector are in some way implicated, as they must also be in transovarially transmitted viruses. However, the causal relationships between virus infectivity and vector physiology are poorly understood. As with virus infections, those disease organisms possessing a cyclical host/vector relationship will possess a variable infectivity potential which is not necessarily related to the abundance of any of the organisms in the cycle. Clearly, feeding behavior and host preferences of the vector are important in determining the rate and extent of disease transmission, and such parameters can be quantified in epidemiological studies. However, a complete understanding of the factors concerned in cyclical disease transmission also depends on a knowledge of the physiology of the organisms involved, and particularly of the interdependence of their physiologies. The subject is vast, and it is proposed to illustrate the problems involved and the progress made, by reference largely to trypanosome transmission by tsetse flies (Glossina spp.).", "contents": "Pathogen transmission in relation to feeding and digestion by haematophagous Arthropods. The blood feeding habit, especially among opportunist feeders such as tabanids and Stomoxys is known to result in transmission of diseases for which the vectors are not the obligate or alternate hosts. Thus, mechanical transmission of trypanosomes such as T. vivax can occur in cattle herds outside tsetse fly areas where tabanids are actively feeding. In the case of Yaws, mechanical transmission of the spirochaetes by eye flies (Hippelates pallipes) in the West Indies is thought to be most likely. The spirochaetes remain motile in the pharynx and oesophageal diverticula for several hours but are apparently immobilised in the midgut (Kumm & Turner, 1936). There is apparently no development ofspirochaetes in the fly. They have been shown to pass through houseflies, but in mechanical transmission, biochemical transformation or adaptation of the pathogen is not implied. Virus transmission is common among arthropods and transovarial transmission to succeeding generations is frequent in mites and ticks. Although Yellow Fever virus is not transovarially transmitted by its vector Aedes aegypti, the mosquito only becomes infective some time after ingesting an infected blood meal (Chandler, 1955). Thus, metabolic or biochemical changes or adaptations in the virus or in the vector are in some way implicated, as they must also be in transovarially transmitted viruses. However, the causal relationships between virus infectivity and vector physiology are poorly understood. As with virus infections, those disease organisms possessing a cyclical host/vector relationship will possess a variable infectivity potential which is not necessarily related to the abundance of any of the organisms in the cycle. Clearly, feeding behavior and host preferences of the vector are important in determining the rate and extent of disease transmission, and such parameters can be quantified in epidemiological studies. However, a complete understanding of the factors concerned in cyclical disease transmission also depends on a knowledge of the physiology of the organisms involved, and particularly of the interdependence of their physiologies. The subject is vast, and it is proposed to illustrate the problems involved and the progress made, by reference largely to trypanosome transmission by tsetse flies (Glossina spp.)."}
{"id": "PMID:240258", "title": "Skin-piercing blood-sucking moths I: ecological and ethological studies on Calpe eustrigata (Lepid., noctuidae).", "content": "The Noctuid Calpe [Calyptral] eustrigata Hmps. was reported as a skin-piercing blood-sucking moth for the first time in Malaya (B\u00e4nziger, 1968) and is so far the only lepidopteran proved to suck blood by means of a piercing act. A few field observations and the description of the piercing behaviour of caged moths were given. Apart from a taxonomic study of the genus Calpe (Berio, 1956), a single record (B\u00fcttiker, 1969) and some notes on the moth's proboscis and possible evolutionary pathway (B\u00e4nziger, 1970, 1971, 1972) to our knowledge no other data have been published on the moth after its description as a new species (Hampson, 1926). The life cycle is completely unknown. From the scanty museum specimens available, it appears that the species inhabits South and Southeast Asia. A closely related, though less rare species, the fruit-piercing C. thalictri Bkh., has been used for a detailed study of the piercing mechanism likely to be adopted by Calpe (B\u00e4nziger, 1970); the feeding turned out to be as unusual as the feeding habits. Little or nothing is known about other Calpe species. C. eustrigata is not the only adult lepidopterous parasite of mammals. Lachryphagous (\"eye-frequenting\") moths feed as \"marginal\" parasites upon eye-secretions of ungulates, elephants and occasionally man (Shannon, 1928; Reid, 1954; B\u00fcttiker, 1964, 1967; B\u00e4nziger, 1966). Arcyophora species and the eulachryphagous Noctuid Lobocraspis graseifusa Hmps. which apparently feeds exclusively upon eye discharges, are suspected as vectors of eye diseases (Guilbride et al., 1959, B\u00fcttiker, 1964; B\u00e4nziger, 1972). While no lachryphagous moth is able to suck blood by a piercing act, there are a number of facultative lachryphagous moths which lick up the blood freely present at wounds, or that excreted anally by mosquitoes (B\u00e4nziger, 1969, 1972). Because of the scientific interest in C. eustrigata, research has been carried out to investigate different biological aspects of the species in Malaysia, Thailand. Laos and Indonesia (May 1971-May 1973). The first account presented here will be continued with a paper (in prep.) on the piercing mechanism and soon, it is hoped, with more information on the physiology, life cycle and medical importance of the moth.", "contents": "Skin-piercing blood-sucking moths I: ecological and ethological studies on Calpe eustrigata (Lepid., noctuidae). The Noctuid Calpe [Calyptral] eustrigata Hmps. was reported as a skin-piercing blood-sucking moth for the first time in Malaya (B\u00e4nziger, 1968) and is so far the only lepidopteran proved to suck blood by means of a piercing act. A few field observations and the description of the piercing behaviour of caged moths were given. Apart from a taxonomic study of the genus Calpe (Berio, 1956), a single record (B\u00fcttiker, 1969) and some notes on the moth's proboscis and possible evolutionary pathway (B\u00e4nziger, 1970, 1971, 1972) to our knowledge no other data have been published on the moth after its description as a new species (Hampson, 1926). The life cycle is completely unknown. From the scanty museum specimens available, it appears that the species inhabits South and Southeast Asia. A closely related, though less rare species, the fruit-piercing C. thalictri Bkh., has been used for a detailed study of the piercing mechanism likely to be adopted by Calpe (B\u00e4nziger, 1970); the feeding turned out to be as unusual as the feeding habits. Little or nothing is known about other Calpe species. C. eustrigata is not the only adult lepidopterous parasite of mammals. Lachryphagous (\"eye-frequenting\") moths feed as \"marginal\" parasites upon eye-secretions of ungulates, elephants and occasionally man (Shannon, 1928; Reid, 1954; B\u00fcttiker, 1964, 1967; B\u00e4nziger, 1966). Arcyophora species and the eulachryphagous Noctuid Lobocraspis graseifusa Hmps. which apparently feeds exclusively upon eye discharges, are suspected as vectors of eye diseases (Guilbride et al., 1959, B\u00fcttiker, 1964; B\u00e4nziger, 1972). While no lachryphagous moth is able to suck blood by a piercing act, there are a number of facultative lachryphagous moths which lick up the blood freely present at wounds, or that excreted anally by mosquitoes (B\u00e4nziger, 1969, 1972). Because of the scientific interest in C. eustrigata, research has been carried out to investigate different biological aspects of the species in Malaysia, Thailand. Laos and Indonesia (May 1971-May 1973). The first account presented here will be continued with a paper (in prep.) on the piercing mechanism and soon, it is hoped, with more information on the physiology, life cycle and medical importance of the moth."}
{"id": "PMID:240259", "title": "Haemolytic activity in the blood clot of Aedes aegypti.", "content": "In the present study it was demonstrated that mosquito blood clots contain a haemolytic principle which achieves haemolysis of washed erythrocytes in an isotonic medium. Proteinases are thought to play a role in this process. No final proof could be given for the existence of phospholipase activity although some results suggest the presence of this group of enzymes.", "contents": "Haemolytic activity in the blood clot of Aedes aegypti. In the present study it was demonstrated that mosquito blood clots contain a haemolytic principle which achieves haemolysis of washed erythrocytes in an isotonic medium. Proteinases are thought to play a role in this process. No final proof could be given for the existence of phospholipase activity although some results suggest the presence of this group of enzymes."}
{"id": "PMID:240260", "title": "Effects of carbon dioxide anaesthetic on Glossina.", "content": "Exposure of 2 day old virgin females of Glossina fuscipes fuscipes, G. pallidipes, G. brevipalpis, and G. morsitans centralis to carbon dioxide anaesthesia for 15 sec has the effect of suppressing their subsequent insemination frequency. This insemination-inhibitory effect of the gas is more pronounced in G. f. fuscipes and G. pallidipes than in G. brevipalpis and G. m. centralis. In G.f. fuscipes the adverse effect on insemination persists, albeit to a lesser degree, at least up to 72 hr. Carbon dioxide anaesthesia also reduces the insemination capability of G.f. fuscipes males; this effect, however, is less marked than in females. Exposure of wild non-teneral G.f. fuscipes, G. pallidipes, G. brevipalpis, and 3 day old G.m. centralis to the gas for 30 min causes some mortality during anaesthesia, which increases with increasing exposure period. G. m. centralis is most tolerant to the lethal effect of the gas within the 10-90 min exposure periods. Wild females of G.f. fuscipes and G. pallidipes seem to be more sensitive to carbon dioxide in this report than males. In view of these adverse effects produced by carbon dioxide anaesthesia, its use on tsetse is not to be recommended.", "contents": "Effects of carbon dioxide anaesthetic on Glossina. Exposure of 2 day old virgin females of Glossina fuscipes fuscipes, G. pallidipes, G. brevipalpis, and G. morsitans centralis to carbon dioxide anaesthesia for 15 sec has the effect of suppressing their subsequent insemination frequency. This insemination-inhibitory effect of the gas is more pronounced in G. f. fuscipes and G. pallidipes than in G. brevipalpis and G. m. centralis. In G.f. fuscipes the adverse effect on insemination persists, albeit to a lesser degree, at least up to 72 hr. Carbon dioxide anaesthesia also reduces the insemination capability of G.f. fuscipes males; this effect, however, is less marked than in females. Exposure of wild non-teneral G.f. fuscipes, G. pallidipes, G. brevipalpis, and 3 day old G.m. centralis to the gas for 30 min causes some mortality during anaesthesia, which increases with increasing exposure period. G. m. centralis is most tolerant to the lethal effect of the gas within the 10-90 min exposure periods. Wild females of G.f. fuscipes and G. pallidipes seem to be more sensitive to carbon dioxide in this report than males. In view of these adverse effects produced by carbon dioxide anaesthesia, its use on tsetse is not to be recommended."}
{"id": "PMID:240265", "title": "Comparative systemic and regional hemodynamic effects of dopamine and dobutamine.", "content": "Dopamine and dobutamine are sympathomimetic amines with divergent peripheral vascular actions. The renal, mesenteric, and femoral vascular and total systemic hemodynamic effects of these amines were compared in pentobarbital-anesthetized dogs. Both agents increased myocardial contractility. Infusion rates of dopamine greater than 5 mug per kilogram per minute increased mean aortic pressure. Dobutamine increased mean aortic pressure. Dobutamine in creased the systolic pressure but did not alter mean aortic pressure. Dobutamine increased cardiac output more than dopamine. Dopamine infusions up to 10 mug per kilogram per minute increased renal and mesenteric blood flow and decreased vascular resistance. Dobutamine had negligible effects on the renal or mesenteric blood flow but produced dose-related increases in femoral blood flow. Dopamine did not significantly alter femoral hemodynamics. These results more clearly define the systemic and regional vascular hemodynamic effects of these agents.", "contents": "Comparative systemic and regional hemodynamic effects of dopamine and dobutamine. Dopamine and dobutamine are sympathomimetic amines with divergent peripheral vascular actions. The renal, mesenteric, and femoral vascular and total systemic hemodynamic effects of these amines were compared in pentobarbital-anesthetized dogs. Both agents increased myocardial contractility. Infusion rates of dopamine greater than 5 mug per kilogram per minute increased mean aortic pressure. Dobutamine increased mean aortic pressure. Dobutamine in creased the systolic pressure but did not alter mean aortic pressure. Dobutamine increased cardiac output more than dopamine. Dopamine infusions up to 10 mug per kilogram per minute increased renal and mesenteric blood flow and decreased vascular resistance. Dobutamine had negligible effects on the renal or mesenteric blood flow but produced dose-related increases in femoral blood flow. Dopamine did not significantly alter femoral hemodynamics. These results more clearly define the systemic and regional vascular hemodynamic effects of these agents."}
{"id": "PMID:240266", "title": "Paroxysmal hypertension in aortitis syndrome.", "content": "Three patients with aortitis syndrome ehibited paroxysmal hypertension which seemed to result from baroreceptor dysfunction. All of the patients had signs of active inflammation of aortitis syndrome and stenotic carotid and subclavian arteries. During the attacks, the blood pressure rose to at least 230 mm. Hg systolic and the heart rate exceeded 100. However, with prolonged administration of steroid hormones, the attacks ceased. In two patients with dilated thoracic aortas and aortic regurgitation, the attacks of paroxysmal hypertension occurred without apparent precipitating factors and were followed by anginal pain with marked ST depression. The sympathicotonic state resulting from the disturbance of the baroreceptors was considered to be responsible for the attacks. In another patient, the attacks occurred in the course of treatment with a steroid hormone and were provoked only by voluntary micturition. This post-micturition hypertension was presumed to be an expression of abnormal overshooting following a fall in blood pressure after voiding.", "contents": "Paroxysmal hypertension in aortitis syndrome. Three patients with aortitis syndrome ehibited paroxysmal hypertension which seemed to result from baroreceptor dysfunction. All of the patients had signs of active inflammation of aortitis syndrome and stenotic carotid and subclavian arteries. During the attacks, the blood pressure rose to at least 230 mm. Hg systolic and the heart rate exceeded 100. However, with prolonged administration of steroid hormones, the attacks ceased. In two patients with dilated thoracic aortas and aortic regurgitation, the attacks of paroxysmal hypertension occurred without apparent precipitating factors and were followed by anginal pain with marked ST depression. The sympathicotonic state resulting from the disturbance of the baroreceptors was considered to be responsible for the attacks. In another patient, the attacks occurred in the course of treatment with a steroid hormone and were provoked only by voluntary micturition. This post-micturition hypertension was presumed to be an expression of abnormal overshooting following a fall in blood pressure after voiding."}
{"id": "PMID:240269", "title": "Serum gamma-glutamyl transpeptidase. Evaluation in screening of hospitalized patients.", "content": "Evaluation in screening of hospitalized patients. Am J Clin Pathol 64: 311-314, 1975. The specificity of the serum gamma-glutamyl transpepidase (GGT) was evaluated by its determination in 1,040 unselected adult inpatients. GGT was elevated in 139 (13.4%) patients, but was only rarely elevated in the absence of elevation of other enzymes in the routine chemistry profile. Of the elevations, 32.4% occurred in patients with primary hepatobiliary disease. An elevated serum GGT is a strong indicator of hepatobiliary dysfunction. However, proper interpretation of a serum GGT elevation requires correlation with clinical data and other tests.", "contents": "Serum gamma-glutamyl transpeptidase. Evaluation in screening of hospitalized patients. Evaluation in screening of hospitalized patients. Am J Clin Pathol 64: 311-314, 1975. The specificity of the serum gamma-glutamyl transpepidase (GGT) was evaluated by its determination in 1,040 unselected adult inpatients. GGT was elevated in 139 (13.4%) patients, but was only rarely elevated in the absence of elevation of other enzymes in the routine chemistry profile. Of the elevations, 32.4% occurred in patients with primary hepatobiliary disease. An elevated serum GGT is a strong indicator of hepatobiliary dysfunction. However, proper interpretation of a serum GGT elevation requires correlation with clinical data and other tests."}
{"id": "PMID:240270", "title": "Further identification of a D/E translocation.", "content": "An infant previously reported to have psychomotor retardation and multiple congenital anomalies including hypotonia, failure to thrive, peculiar facies, low-set ears, micrognathia, and cryptorchidism in association with monosomy due to a D/E (13-15/17-18) translocation has been reexamined. Further cytogenetic studies, using fluorescent techniques, indicate the translocation involves chromosomes 15 and 17. Only two other patients with partial monosomy due to grossly similar D/E translocations have been reported. On reexamination, the translocation in one has recently been found to involve chromosomes 15 and 18 and that in the other has not been further defined.", "contents": "Further identification of a D/E translocation. An infant previously reported to have psychomotor retardation and multiple congenital anomalies including hypotonia, failure to thrive, peculiar facies, low-set ears, micrognathia, and cryptorchidism in association with monosomy due to a D/E (13-15/17-18) translocation has been reexamined. Further cytogenetic studies, using fluorescent techniques, indicate the translocation involves chromosomes 15 and 17. Only two other patients with partial monosomy due to grossly similar D/E translocations have been reported. On reexamination, the translocation in one has recently been found to involve chromosomes 15 and 18 and that in the other has not been further defined."}
{"id": "PMID:240271", "title": "Characterization of Hex S, the major residual beta hexosaminidase activity in type O Gm2 gangliosidosis (Sandhoff-Jatzkewitz disease).", "content": "Hex S, the major residual beta hexosaminidase activity present in tissues, fluids, and cultured skin fibroblasts of patients with type 0 GM2 gangliosidosis, was isolated and characterized biochemically and immunologically. when appropriate tissue homogenates were tested by electrophoresis on cellulose acetate gels, hex S as well as hex C, the corresponding minor beta hexosaminidase component found in normal visceral tissues, migrated with greater anodic mobilities than hex A. However, a small but reproducible electrophoretic difference was observed between partially purified hex S and hex C components. Hex S and hex C had slightly higher apparent molecular weights than those of hex A or hex G; no major differences were found between hex S and hex A in thermostability, pH optimum, or kinetic properties. Hex S, like hex C from placenta, reacted with an antiserum directed towards the unique antigenic determinants alpha of hex A, indicating that hex S, hex C, and hex A share a common antigenic determinant. No reactivity of hex S was detected with an antiserum directed toward the common antigenic determinant beta of hex A and hex B. These results suggest that further biochemical and immunologic characterization of hex S and elucidation of its relationships with hex A, hex B, and hex C may significantly contribute to the understanding of the molecular defects in the GM2 gangliosidoses.", "contents": "Characterization of Hex S, the major residual beta hexosaminidase activity in type O Gm2 gangliosidosis (Sandhoff-Jatzkewitz disease). Hex S, the major residual beta hexosaminidase activity present in tissues, fluids, and cultured skin fibroblasts of patients with type 0 GM2 gangliosidosis, was isolated and characterized biochemically and immunologically. when appropriate tissue homogenates were tested by electrophoresis on cellulose acetate gels, hex S as well as hex C, the corresponding minor beta hexosaminidase component found in normal visceral tissues, migrated with greater anodic mobilities than hex A. However, a small but reproducible electrophoretic difference was observed between partially purified hex S and hex C components. Hex S and hex C had slightly higher apparent molecular weights than those of hex A or hex G; no major differences were found between hex S and hex A in thermostability, pH optimum, or kinetic properties. Hex S, like hex C from placenta, reacted with an antiserum directed towards the unique antigenic determinants alpha of hex A, indicating that hex S, hex C, and hex A share a common antigenic determinant. No reactivity of hex S was detected with an antiserum directed toward the common antigenic determinant beta of hex A and hex B. These results suggest that further biochemical and immunologic characterization of hex S and elucidation of its relationships with hex A, hex B, and hex C may significantly contribute to the understanding of the molecular defects in the GM2 gangliosidoses."}
{"id": "PMID:240276", "title": "The role of cytolysin in pneumococcal ocular infection.", "content": "A highly purified preparation of pneumococcal cytolysin was responsible for the corneal damage that ensued upon intra-corneal injection of crude cell extract into the rabbit eye. The lysin may produce this pathologic finding by effecting activation or release of corneal degradative enzymes.", "contents": "The role of cytolysin in pneumococcal ocular infection. A highly purified preparation of pneumococcal cytolysin was responsible for the corneal damage that ensued upon intra-corneal injection of crude cell extract into the rabbit eye. The lysin may produce this pathologic finding by effecting activation or release of corneal degradative enzymes."}
{"id": "PMID:240277", "title": "Cardiac and respiratory effects of digitalis during chronic hypoxia in intact conscious dogs.", "content": "The arrhythmogenic and respiratory effects of ouabain during chronic hypoxia were studied in 10 unanesthetized dogs in a hypobaric chamber (446 mmHg) following 7-19 (mean 14.7) days of continuous exposure at this altitude. Another 15 dogs studied at sea level comprised the normoxic control group. In both groups, a 7.5-mug/kg loading dose of ouabain was followed by infusion of ouabain at 3.0 mug/kg per min to ECG evidence of toxicity. Mean arterial Po2 was 46 +/- 5 mmHg in chronically hypoxic dogs as compared to 86 +/- 7 mmHg in normoxic animals (P less than 0.001). Mean hematocrit was 54 +/- 1% in hypoxic and 43 +/- 2% in normoxic groups (P less than 0.001). In five dogs studied first at sea level and subsequently under conditions of chronic hypoxia, mean maximum left ventricular dP/dt and peak (dP/dt)P-1 were unchanged. Marked hyperventilation during ouabain infusion was observed. In normoxic dogs mean arterial pH rose from 7.43 +/- 0.05 to 7.70 +/- 0.02 U, and Pco2 fell from 41 +/- 4 to 15 +/- 1 mmHg during ouabain administration (P less than 0.001). Similar changes were observed in hypoxic dogs. There was no significant difference in the mean toxic dose of ouabain in chronically hypoxic (71 +/- 11 mug/kg) versus normoxic (78 +/- 12 mug/kg) animals. Thus, in contrast to acute hypoxia, chronic hypoxia in unanesthetized dogs was not associated with a significant reduction in the dose of ouabain required to produce toxic arrhythmias. Chronic hypoxia was also not associated with alterations in left ventricular performance.", "contents": "Cardiac and respiratory effects of digitalis during chronic hypoxia in intact conscious dogs. The arrhythmogenic and respiratory effects of ouabain during chronic hypoxia were studied in 10 unanesthetized dogs in a hypobaric chamber (446 mmHg) following 7-19 (mean 14.7) days of continuous exposure at this altitude. Another 15 dogs studied at sea level comprised the normoxic control group. In both groups, a 7.5-mug/kg loading dose of ouabain was followed by infusion of ouabain at 3.0 mug/kg per min to ECG evidence of toxicity. Mean arterial Po2 was 46 +/- 5 mmHg in chronically hypoxic dogs as compared to 86 +/- 7 mmHg in normoxic animals (P less than 0.001). Mean hematocrit was 54 +/- 1% in hypoxic and 43 +/- 2% in normoxic groups (P less than 0.001). In five dogs studied first at sea level and subsequently under conditions of chronic hypoxia, mean maximum left ventricular dP/dt and peak (dP/dt)P-1 were unchanged. Marked hyperventilation during ouabain infusion was observed. In normoxic dogs mean arterial pH rose from 7.43 +/- 0.05 to 7.70 +/- 0.02 U, and Pco2 fell from 41 +/- 4 to 15 +/- 1 mmHg during ouabain administration (P less than 0.001). Similar changes were observed in hypoxic dogs. There was no significant difference in the mean toxic dose of ouabain in chronically hypoxic (71 +/- 11 mug/kg) versus normoxic (78 +/- 12 mug/kg) animals. Thus, in contrast to acute hypoxia, chronic hypoxia in unanesthetized dogs was not associated with a significant reduction in the dose of ouabain required to produce toxic arrhythmias. Chronic hypoxia was also not associated with alterations in left ventricular performance."}
{"id": "PMID:240278", "title": "Hemodynamics and blood flow distribution following prolonged circulation at 5 degrees C.", "content": "Circulation was maintained in profoundly hypothermic dogs for 8 h at temperatures below 10 degrees C. During cooling to 5 degrees C cardiac output and blood pressure decreased and peripheral resistance rose. Thereafter, circulatory dynamics remained relatively stable over the next 6 h with a gradual decline in blood pressure. The proportion of blood flow to the heart and brain increased with cooling and remained elevated throughout the hypothermia period. Despite continued circulation, pulmonary edema developed after 5-7 h and the dogs were nonviable when rewarmed.", "contents": "Hemodynamics and blood flow distribution following prolonged circulation at 5 degrees C. Circulation was maintained in profoundly hypothermic dogs for 8 h at temperatures below 10 degrees C. During cooling to 5 degrees C cardiac output and blood pressure decreased and peripheral resistance rose. Thereafter, circulatory dynamics remained relatively stable over the next 6 h with a gradual decline in blood pressure. The proportion of blood flow to the heart and brain increased with cooling and remained elevated throughout the hypothermia period. Despite continued circulation, pulmonary edema developed after 5-7 h and the dogs were nonviable when rewarmed."}
{"id": "PMID:240279", "title": "Spinal autonomic afferents in elicitation of tachycardia in volume infusion in the dog.", "content": "Intravenous infusion of blood (36 ml/kg body wt) elicited tachycardia in artificially ventilated anesthetized dogs with intact autonomic innervation and in dogs with cardiac beta-receptor blockade. In contrast, infusion elicited bradycardia in dogs with section of the spinal cord at C6-C7, and in dogs with combined spinal section and cardiac beta-receptor blockade. The control heart rate was less than or equal to 110 beats/min in all the animals. The presence of infusion-induced tachycardia in dogs with beta-receptor blockade, i.e., dogs in which cardiac sympathetic efferents were blocked, and its absence in dogs with combined spinal section and beta-receptor blockade, i.e., dogs in which spinal autonomic afferents plus cardiac sympathetic efferents were blocked, may be the result of an additional interruption of spinal autonomic afferents by spinal section. It is concluded that tachycardia elicited by infusion may be partly due to a reflex with its afferent pathway in the spinal cord and its efferent pathway in the vagus nerves.", "contents": "Spinal autonomic afferents in elicitation of tachycardia in volume infusion in the dog. Intravenous infusion of blood (36 ml/kg body wt) elicited tachycardia in artificially ventilated anesthetized dogs with intact autonomic innervation and in dogs with cardiac beta-receptor blockade. In contrast, infusion elicited bradycardia in dogs with section of the spinal cord at C6-C7, and in dogs with combined spinal section and cardiac beta-receptor blockade. The control heart rate was less than or equal to 110 beats/min in all the animals. The presence of infusion-induced tachycardia in dogs with beta-receptor blockade, i.e., dogs in which cardiac sympathetic efferents were blocked, and its absence in dogs with combined spinal section and beta-receptor blockade, i.e., dogs in which spinal autonomic afferents plus cardiac sympathetic efferents were blocked, may be the result of an additional interruption of spinal autonomic afferents by spinal section. It is concluded that tachycardia elicited by infusion may be partly due to a reflex with its afferent pathway in the spinal cord and its efferent pathway in the vagus nerves."}
{"id": "PMID:240280", "title": "Inotropic responses to digoxin during hypoxia and autonomic blockade.", "content": "Inotropic responses to digoxin (0.08 mg/kg) were studied in dogs and compared with responses during hypoxemia and autonomic blockade. Changes in left ventricular contractility (VC) were assessed by constructing function curves relating left ventricular (dP/dt)max and stroke volume to end-diastolic pressure. Augmentation of VC was observed 20 min after digoxin infusion and continued to increase until termination of the experiment after 60 min. In animals subjected to autonomic blockade with practolol, TEAC, and atropine, the increases in VC after digoxin were substantially greater. Equally large increases occurred in blocked dogs during sustained hypoxia (Pao2 = 28 mmHg). However, in animals without blockade there was a progressive fall in VC during hypoxia despite digoxin infusion, although less than in those not given digoxin. Serum digoxin levels were measured by radioimmunoassay and did not differ significantly in blocked compared to unblocked dogs or in hypoxic compared to nonhypoxic animals. These findings indicate that digoxin protects the heart from the decrease in myocardial contractility which occurs during extended hypoxia. This protective effect is more pronounced in animals deprived of autonomic function, possibly reflecting the elimination of reflex sympathetic withdrawal ordinarily induced by digitalis.", "contents": "Inotropic responses to digoxin during hypoxia and autonomic blockade. Inotropic responses to digoxin (0.08 mg/kg) were studied in dogs and compared with responses during hypoxemia and autonomic blockade. Changes in left ventricular contractility (VC) were assessed by constructing function curves relating left ventricular (dP/dt)max and stroke volume to end-diastolic pressure. Augmentation of VC was observed 20 min after digoxin infusion and continued to increase until termination of the experiment after 60 min. In animals subjected to autonomic blockade with practolol, TEAC, and atropine, the increases in VC after digoxin were substantially greater. Equally large increases occurred in blocked dogs during sustained hypoxia (Pao2 = 28 mmHg). However, in animals without blockade there was a progressive fall in VC during hypoxia despite digoxin infusion, although less than in those not given digoxin. Serum digoxin levels were measured by radioimmunoassay and did not differ significantly in blocked compared to unblocked dogs or in hypoxic compared to nonhypoxic animals. These findings indicate that digoxin protects the heart from the decrease in myocardial contractility which occurs during extended hypoxia. This protective effect is more pronounced in animals deprived of autonomic function, possibly reflecting the elimination of reflex sympathetic withdrawal ordinarily induced by digitalis."}
{"id": "PMID:240281", "title": "Oxygen-linked CO2 transport in sheep blood.", "content": "We have analyzed oxygen-linked carbamate formation in sheep hemoglobin B by measuring a) the effect of CO2 on oxygen affinity and Bohr effect in red cell suspensions and dilute (1.3 mM Hb4) and concentrated (5 mM Hb4) hemoglobin solutions at 37 degrees C and b) CO2 binding curves of deoxygenated and oxygenated whole blood and hemoglobin solutions, respectively, at the same temperature. In the presence of CO2 both the Bohr effect and oxygen affinity were significantly lower in 1.3-mM Hb4 solutions than in either red cell suspensions or 5-mM Hb4 solutions, while in the absence of  CO2 Bohr effect and oxygen affinity did not differ significantly in those preparations. Likewise, the fraction of oxygen-linked carbamate obtained from CO2 binding curves was found to be higher in 1.3-mM Hb4 (0.156 M HbCO2/M HbO2) solutions than in 5-mM Hb4 solutions (0.12 M HbCO2/M HbO2) at pH 7.2. We conclude that hemoglobin concentration affects formation of oxygen-linked carbamate. Total oxygen-linked CO2 in sheep whole blood amounted to 0.18 M CO2/M O2 of which 70% is oxygen-linked carbamate. Assuming a respiratory quotient of 0.85, the contribution of oxygen-linked CO2 to carbon dioxide exchange in sheep blood was computed to be 21%.", "contents": "Oxygen-linked CO2 transport in sheep blood. We have analyzed oxygen-linked carbamate formation in sheep hemoglobin B by measuring a) the effect of CO2 on oxygen affinity and Bohr effect in red cell suspensions and dilute (1.3 mM Hb4) and concentrated (5 mM Hb4) hemoglobin solutions at 37 degrees C and b) CO2 binding curves of deoxygenated and oxygenated whole blood and hemoglobin solutions, respectively, at the same temperature. In the presence of CO2 both the Bohr effect and oxygen affinity were significantly lower in 1.3-mM Hb4 solutions than in either red cell suspensions or 5-mM Hb4 solutions, while in the absence of  CO2 Bohr effect and oxygen affinity did not differ significantly in those preparations. Likewise, the fraction of oxygen-linked carbamate obtained from CO2 binding curves was found to be higher in 1.3-mM Hb4 (0.156 M HbCO2/M HbO2) solutions than in 5-mM Hb4 solutions (0.12 M HbCO2/M HbO2) at pH 7.2. We conclude that hemoglobin concentration affects formation of oxygen-linked carbamate. Total oxygen-linked CO2 in sheep whole blood amounted to 0.18 M CO2/M O2 of which 70% is oxygen-linked carbamate. Assuming a respiratory quotient of 0.85, the contribution of oxygen-linked CO2 to carbon dioxide exchange in sheep blood was computed to be 21%."}
{"id": "PMID:240282", "title": "Effect of norepinephrine on myocardial intracellular hydrogen ion concentration.", "content": "The effect of norepinephrine (NE) on the intracellular hydrogen ion concentration [H+]i of isolated rat hearts perfused with a modified Krebs-Henseleit solution (SHS) was determined. The [H+]i was calculated with the [14C]-dimethyloxazolidinedione method. Respiratory or metabolic acidosis was produced by equilibrating the KHS with 20% C02 or decreasing the [HC03-] of the KHS, respectively. Three types of experiments were carried out: 1) beta blockade--MJ 1999 (Sotalol) was added to the KHS; 2) control--no pharmacological treatment; and 3) NE-norepinephrine was added to the KHS. The effective CO2 buffer values (delta[HC03-]i/deltapHi) during respiratory acidosis were: beta blockade, 11; control, 35; and NE, 84. The production of metabolic acidosis resulted in the following [H+]i changes: beta blockade, 52 mM; control, 60 nM; and NE 7 nM. These results suggest that NE markedly attenuates the changes in [H+]i accompanying respiratory and metabolic acidosis and may account in part for previous observations that the effective C02 buffer value of cardiac muscle in vivo is greater than that in vitro.", "contents": "Effect of norepinephrine on myocardial intracellular hydrogen ion concentration. The effect of norepinephrine (NE) on the intracellular hydrogen ion concentration [H+]i of isolated rat hearts perfused with a modified Krebs-Henseleit solution (SHS) was determined. The [H+]i was calculated with the [14C]-dimethyloxazolidinedione method. Respiratory or metabolic acidosis was produced by equilibrating the KHS with 20% C02 or decreasing the [HC03-] of the KHS, respectively. Three types of experiments were carried out: 1) beta blockade--MJ 1999 (Sotalol) was added to the KHS; 2) control--no pharmacological treatment; and 3) NE-norepinephrine was added to the KHS. The effective CO2 buffer values (delta[HC03-]i/deltapHi) during respiratory acidosis were: beta blockade, 11; control, 35; and NE, 84. The production of metabolic acidosis resulted in the following [H+]i changes: beta blockade, 52 mM; control, 60 nM; and NE 7 nM. These results suggest that NE markedly attenuates the changes in [H+]i accompanying respiratory and metabolic acidosis and may account in part for previous observations that the effective C02 buffer value of cardiac muscle in vivo is greater than that in vitro."}
{"id": "PMID:240283", "title": "Increased cardiac contractility in acute uremia: interrelationships with hypertension.", "content": "To study the effects of acute uremia on the inotropic state of the rat heart, we subjected rats to bilateral nephrectomy and studied their hearts in the open chest 24 h later. Uremic rats had significantly higher systolic blood pressure than sham-operated animals. Left ventricular systolic pressure and maximum dP/dt, both during ejection and isovolumic contrations, were higher for any given end-diastolic pressure in hearts of uremic rats than in sham-operated animals. This difference in performance charcteristics was not abolished by doses of propranolol that blocked the heart rate response to isoproterenol. The administration of phenoxybenzamine during the 24 h of uremia abolished the blood pressure rise in uremic rats, but the increased contractile state persisted. Treatment of sham-operated animals with methoxamine to produce the same course of blood pressure as observed in uremic rats was also associated with an increased inotropic state. These results indicate that in the rat, acute uremia is associated with an increased inotropic state that is not mediated by beta-adrenergic mechanisms. The systolic hypertension of acute uremia is not the major cause of the increased contractility, although systolic hypertension without uremia can mimic the performance characteristics found in hearts of uremic rats.", "contents": "Increased cardiac contractility in acute uremia: interrelationships with hypertension. To study the effects of acute uremia on the inotropic state of the rat heart, we subjected rats to bilateral nephrectomy and studied their hearts in the open chest 24 h later. Uremic rats had significantly higher systolic blood pressure than sham-operated animals. Left ventricular systolic pressure and maximum dP/dt, both during ejection and isovolumic contrations, were higher for any given end-diastolic pressure in hearts of uremic rats than in sham-operated animals. This difference in performance charcteristics was not abolished by doses of propranolol that blocked the heart rate response to isoproterenol. The administration of phenoxybenzamine during the 24 h of uremia abolished the blood pressure rise in uremic rats, but the increased contractile state persisted. Treatment of sham-operated animals with methoxamine to produce the same course of blood pressure as observed in uremic rats was also associated with an increased inotropic state. These results indicate that in the rat, acute uremia is associated with an increased inotropic state that is not mediated by beta-adrenergic mechanisms. The systolic hypertension of acute uremia is not the major cause of the increased contractility, although systolic hypertension without uremia can mimic the performance characteristics found in hearts of uremic rats."}
{"id": "PMID:240284", "title": "Blood oxygen affinity and alveolar ventilation in relation in body weight in mammals.", "content": "The validity of the concept relating blood oxygen affinity and alveolar ventilation to body weight in homeothermic mammals was reexamined with blood pH used as the fixed variable. Blood Po2 at 50% saturation at pH 7.4 (P50(7.4)) and PCO2 of oxygenated blood at pH 7.4 (PCO2(7.4)) from a variety of homeothermic mammals were determined at 37 degrees C by in vitro equilibration techniques. In some species, arterial PCO2, PO2, and pH were also measured. PCO2(7.4), which was similar to arterial PCO2, showed a correlation coefficient of +0.33 with body weight over the range of 28-100,000 g and +0.90 among the species under 200 g. P50(7.4) values, which ranged from 26.0 to 38.7 mmHg for all the species, were not well correlated (r = -0.43) with body weight. For the small mammals (less than 200 g) the correlation coefficient was -0.91. In vivo P50 at the body temperature and arterial pH, although different from P50(7.4), showed a similar correlation with body weight. The lack of valid generalization suggests that body weight is only one of the composite factors that influence O2 transport systems.", "contents": "Blood oxygen affinity and alveolar ventilation in relation in body weight in mammals. The validity of the concept relating blood oxygen affinity and alveolar ventilation to body weight in homeothermic mammals was reexamined with blood pH used as the fixed variable. Blood Po2 at 50% saturation at pH 7.4 (P50(7.4)) and PCO2 of oxygenated blood at pH 7.4 (PCO2(7.4)) from a variety of homeothermic mammals were determined at 37 degrees C by in vitro equilibration techniques. In some species, arterial PCO2, PO2, and pH were also measured. PCO2(7.4), which was similar to arterial PCO2, showed a correlation coefficient of +0.33 with body weight over the range of 28-100,000 g and +0.90 among the species under 200 g. P50(7.4) values, which ranged from 26.0 to 38.7 mmHg for all the species, were not well correlated (r = -0.43) with body weight. For the small mammals (less than 200 g) the correlation coefficient was -0.91. In vivo P50 at the body temperature and arterial pH, although different from P50(7.4), showed a similar correlation with body weight. The lack of valid generalization suggests that body weight is only one of the composite factors that influence O2 transport systems."}
{"id": "PMID:240288", "title": "[Quantitative determination of aqueous humor proteins by electroimmodiffusion in an antiserum containing agarosegel (author's transl)].", "content": "An exact quantitation of aqueous humor proteins within a few hours can be attained by an modification of the quantitative estimation of the proteins by electrophoresis in agarose gel established by Laurell. The aqueous humor proteins form long immunoprecipitations in agargel. The length of the precipitats is proportional to the concentration. By determination of albumin, coeruloplasmin and transferrin the application can be pointed out.", "contents": "[Quantitative determination of aqueous humor proteins by electroimmodiffusion in an antiserum containing agarosegel (author's transl)]. An exact quantitation of aqueous humor proteins within a few hours can be attained by an modification of the quantitative estimation of the proteins by electrophoresis in agarose gel established by Laurell. The aqueous humor proteins form long immunoprecipitations in agargel. The length of the precipitats is proportional to the concentration. By determination of albumin, coeruloplasmin and transferrin the application can be pointed out."}
{"id": "PMID:240298", "title": "Low plasma ionized calcium and response to calcium therapy in critically ill man.", "content": "Marked lowering of plasma ionized calcium concentrations [Ca++] occurred in eight patients (2 days to 54 years old) who required extensive pharmacologic support of the circulation. [Ca++]'s ranged from 0.21 to 0.53 mM. Only one patient survived. The hypocalcemia occurred in the absence of massive transfusion of citrated whole blood or well after such transfusions had been discontinued. These abnormally low concentrations of ionized calcium were not readily corrected by intravenous administration of calcium salts in doses generally recommended. The process responsible for inadequate hemodynamic function appeared to be associated with a severe disturbance in calcium metabolism. Contribution of the latter to the severity of hemodynamic deterioration is unclear, and little benefit from intravenous calcium therapy was found. In two patients, normal [Ca++] could not be restored by administration of CaCl2 alone, but [Ca++] rose to normal following continued calcium replacement therapy in conjunction with increased isoproterenol infusion. There was no predictable relationship between total and ionized plasma calcium concentrations. Thus, measurement of total calcium provided no indication of the level of the biologically active moiety. [Ca++] was low with both normal and low plasma pH values. The data suggest that a very high infusion rate of CaCl2 may required to restore [Ca++] to normal and that hypocalcemia occurring during low-flow states often cannot be corrected by calcium therapy alone. It is recommended that calcium replacement therapy be undertaken only with close monitoring of [Ca++].", "contents": "Low plasma ionized calcium and response to calcium therapy in critically ill man. Marked lowering of plasma ionized calcium concentrations [Ca++] occurred in eight patients (2 days to 54 years old) who required extensive pharmacologic support of the circulation. [Ca++]'s ranged from 0.21 to 0.53 mM. Only one patient survived. The hypocalcemia occurred in the absence of massive transfusion of citrated whole blood or well after such transfusions had been discontinued. These abnormally low concentrations of ionized calcium were not readily corrected by intravenous administration of calcium salts in doses generally recommended. The process responsible for inadequate hemodynamic function appeared to be associated with a severe disturbance in calcium metabolism. Contribution of the latter to the severity of hemodynamic deterioration is unclear, and little benefit from intravenous calcium therapy was found. In two patients, normal [Ca++] could not be restored by administration of CaCl2 alone, but [Ca++] rose to normal following continued calcium replacement therapy in conjunction with increased isoproterenol infusion. There was no predictable relationship between total and ionized plasma calcium concentrations. Thus, measurement of total calcium provided no indication of the level of the biologically active moiety. [Ca++] was low with both normal and low plasma pH values. The data suggest that a very high infusion rate of CaCl2 may required to restore [Ca++] to normal and that hypocalcemia occurring during low-flow states often cannot be corrected by calcium therapy alone. It is recommended that calcium replacement therapy be undertaken only with close monitoring of [Ca++]."}
{"id": "PMID:240301", "title": "The effect of local anesthetic, lidocaine, on guinea pig trachealis muscle in vitro.", "content": "The effect of lidocaine was studied in guinea pig trachealis muscle by dose-response reversal and protection of agonist-induced contractures in a superfusion system. Lidocaine reversed histamine, acetylcholine, and depolarizing hypertonic potassium contractures with the median effective doses of 2.8, 6.0, and 3.2 mg. Lidocaine presuperfusion shifted in a nonparallel fashion (P less than 0.05) the dose-response of histamine, acetylcholine, depolarizing potassium, and supramaximal electrical stimulation by contact electrodes. Pretreatment with 7 x 10(-6) M atropine did not modify lidocaine's inhibition of the hypertonic potassium contractions. These findings and the decrease in maximal response indicated noncompetitive antagonism. In contrast to isoproterenol, the action of lidocaine was not influenced by beta-blockade induced by superfusate propranolol, 1.0 mug per ml (P = 0.2). Lidocaine's effect on trachealis smooth muscle was facilitated by a decrease in hydrogen ion activity from pH 6.71 to 7.90, consistent with enhanced penetration of the free base. Low bolus dose lidocaine-induced contractures were noted in many studies. The potency of isoproterenol in comparison to lidocaine, as indexed by median effective doses, was 10(5) greater for reversal of histamine contractures and 10(4) greater for acetylcholine. The data were consistent with a nonspecific, reversible antagonism on the smooth muscle cell and may involve an effect on calcium activity.", "contents": "The effect of local anesthetic, lidocaine, on guinea pig trachealis muscle in vitro. The effect of lidocaine was studied in guinea pig trachealis muscle by dose-response reversal and protection of agonist-induced contractures in a superfusion system. Lidocaine reversed histamine, acetylcholine, and depolarizing hypertonic potassium contractures with the median effective doses of 2.8, 6.0, and 3.2 mg. Lidocaine presuperfusion shifted in a nonparallel fashion (P less than 0.05) the dose-response of histamine, acetylcholine, depolarizing potassium, and supramaximal electrical stimulation by contact electrodes. Pretreatment with 7 x 10(-6) M atropine did not modify lidocaine's inhibition of the hypertonic potassium contractions. These findings and the decrease in maximal response indicated noncompetitive antagonism. In contrast to isoproterenol, the action of lidocaine was not influenced by beta-blockade induced by superfusate propranolol, 1.0 mug per ml (P = 0.2). Lidocaine's effect on trachealis smooth muscle was facilitated by a decrease in hydrogen ion activity from pH 6.71 to 7.90, consistent with enhanced penetration of the free base. Low bolus dose lidocaine-induced contractures were noted in many studies. The potency of isoproterenol in comparison to lidocaine, as indexed by median effective doses, was 10(5) greater for reversal of histamine contractures and 10(4) greater for acetylcholine. The data were consistent with a nonspecific, reversible antagonism on the smooth muscle cell and may involve an effect on calcium activity."}
{"id": "PMID:240308", "title": "Association of enteroviruses with natural and artificially introduced colloidal solids in water and infectivity of solids-associated virions.", "content": "Encephalomyocarditis viruses adsorb to introducted organic and inorganic solids in water over a wide range of pH and with various concentrations and species of metal cations. Visible flocculation of solids was not a prerequisite for significant virus association. Virus adsorption to natural solids in various types of natural waters was significant but variable. Clay-adsorbed virus retained its infectivity in tissue culture monolayers. These solids-associated viruses also retained infectivity in mice.", "contents": "Association of enteroviruses with natural and artificially introduced colloidal solids in water and infectivity of solids-associated virions. Encephalomyocarditis viruses adsorb to introducted organic and inorganic solids in water over a wide range of pH and with various concentrations and species of metal cations. Visible flocculation of solids was not a prerequisite for significant virus association. Virus adsorption to natural solids in various types of natural waters was significant but variable. Clay-adsorbed virus retained its infectivity in tissue culture monolayers. These solids-associated viruses also retained infectivity in mice."}
{"id": "PMID:240310", "title": "Chemostat culture of Escherichia coli K-12 limited by the activity of alkaline phosphatase.", "content": "The growth-limiting reaction of a chemostat culture of Escherichia coli K-12 was the hydrolysis of beta-glycerophosphate by alkaline phosphatase. The culture was buffered at pH 5.2 where alkaline phosphatase was unable to supply phosphate to the cell at a rate sufficient to sustain the maximum rate of growth. Alkaline phosphatase activity in this system is discussed in terms of the so-called Flip-Flop mechanism.", "contents": "Chemostat culture of Escherichia coli K-12 limited by the activity of alkaline phosphatase. The growth-limiting reaction of a chemostat culture of Escherichia coli K-12 was the hydrolysis of beta-glycerophosphate by alkaline phosphatase. The culture was buffered at pH 5.2 where alkaline phosphatase was unable to supply phosphate to the cell at a rate sufficient to sustain the maximum rate of growth. Alkaline phosphatase activity in this system is discussed in terms of the so-called Flip-Flop mechanism."}
{"id": "PMID:240309", "title": "Transformation of morphine by resting cells and cell-free systems of Arthrobacter sp.", "content": "Morphine can be transformed into 14-hydroxymorphine and a related unidentified material by resting cells of an Arthrobacter species. Cell-free extracts containing the transforming enzyme(s) have been obtained. O2, Fe2+, and reduced nicotinamide adenine dinucleotide stimulate the transformation.", "contents": "Transformation of morphine by resting cells and cell-free systems of Arthrobacter sp. Morphine can be transformed into 14-hydroxymorphine and a related unidentified material by resting cells of an Arthrobacter species. Cell-free extracts containing the transforming enzyme(s) have been obtained. O2, Fe2+, and reduced nicotinamide adenine dinucleotide stimulate the transformation."}
{"id": "PMID:240311", "title": "Derivation of high enterotoxin B-producing mutants of Staphylococcus aureus from the parent strains.", "content": "Certain pH-sensitive (membrane) mutants of Staphylococcus aureus, strains 14458 and 778, produce significantly more type-B enterotoxin (SEB) than the parent type. Some carbohydrate mutants (car) from these parent strains also are superior to the parent in SEB formation. By isolating car mutants from high-SEB-producing membrane mutants, it is possible to derive a double mutant producing from six to 50 times as much SEB as the parent type. Inversion of the sequence by isolating pH-sensitive mutants from car mutants does not yield clones with strikingly higher SEB production than the parent strain. The successful isolation sequence (pH-sensitive mutant first and car mutants derived from it) is relatively simple and virtually assures detection of a truly high-SEB-producing clone. The total number of clones whose direct assay for SEB formation is necessary for detection of a high-producing mutant is on the order of 50 to 60.", "contents": "Derivation of high enterotoxin B-producing mutants of Staphylococcus aureus from the parent strains. Certain pH-sensitive (membrane) mutants of Staphylococcus aureus, strains 14458 and 778, produce significantly more type-B enterotoxin (SEB) than the parent type. Some carbohydrate mutants (car) from these parent strains also are superior to the parent in SEB formation. By isolating car mutants from high-SEB-producing membrane mutants, it is possible to derive a double mutant producing from six to 50 times as much SEB as the parent type. Inversion of the sequence by isolating pH-sensitive mutants from car mutants does not yield clones with strikingly higher SEB production than the parent strain. The successful isolation sequence (pH-sensitive mutant first and car mutants derived from it) is relatively simple and virtually assures detection of a truly high-SEB-producing clone. The total number of clones whose direct assay for SEB formation is necessary for detection of a high-producing mutant is on the order of 50 to 60."}
{"id": "PMID:240307", "title": "[Development in mosquitoes of 3 filaria of the South American lizards of the genus Oswaldofilaria].", "content": "The development of O. petersi, O. belemensis and O. spinosa is similar to that of O. bacillaris: the larvae are in the adipose tissue of various mosquitoes; the infective stages are characterized by the longitudinal salient ridges of the cuticule, the long tail ended by two lappets, the well-developed glandular oesophagus; the female genital anlage lies in the anterior half part of the body, but is not very far from the median line. This character opposes these species to the other viviparous Filariae and stresses the originality of the Oswaldofilariinar.", "contents": "[Development in mosquitoes of 3 filaria of the South American lizards of the genus Oswaldofilaria]. The development of O. petersi, O. belemensis and O. spinosa is similar to that of O. bacillaris: the larvae are in the adipose tissue of various mosquitoes; the infective stages are characterized by the longitudinal salient ridges of the cuticule, the long tail ended by two lappets, the well-developed glandular oesophagus; the female genital anlage lies in the anterior half part of the body, but is not very far from the median line. This character opposes these species to the other viviparous Filariae and stresses the originality of the Oswaldofilariinar."}
{"id": "PMID:240328", "title": "Extraction of lead from printed matter at physiological values of pH.", "content": "In an in vitro laboratory study of the extractability of lead in printed matter it was found that dangerous quantities of lead, up to 200 mug, could be extracted from \"small\" pieces of printed paper at pH values in the range of human gastric fluid. Lead was not extracted at pH values in the range of human saliva. Children who chew printed matter may not be in danger of absorbing lead, but the pica-prone child who swallows printed material may be at risk of absorbing excessive amounts of this toxic metal. The use of printing inks containing high-lead levels should be discouraged.", "contents": "Extraction of lead from printed matter at physiological values of pH. In an in vitro laboratory study of the extractability of lead in printed matter it was found that dangerous quantities of lead, up to 200 mug, could be extracted from \"small\" pieces of printed paper at pH values in the range of human gastric fluid. Lead was not extracted at pH values in the range of human saliva. Children who chew printed matter may not be in danger of absorbing lead, but the pica-prone child who swallows printed material may be at risk of absorbing excessive amounts of this toxic metal. The use of printing inks containing high-lead levels should be discouraged."}
{"id": "PMID:240329", "title": "Sepsis, resuscitated hemorrhagic shock and \"shock lung:\" An experimental correlation.", "content": "Dogs were submitted to hermorrhagic shock, resuscitated shock and resuscitated shock plus a pulmonary bacterial insult. Pulmonary familure was absent in dogs submitted only to shock or to shock and its resuscitation. The addition of usually sub-lethal amounts of micro-organisms to the shock-resuscitated lung caused rapid death from pulmonary failure. Pulmonary failure was demonstrated by increased lung weight, hypoxemia, decreased compliance and a hemorrhagic destruction of lung tissue. These findings strongly support recent concepts of an infective genesis of \"shock lung\" in man.", "contents": "Sepsis, resuscitated hemorrhagic shock and \"shock lung:\" An experimental correlation. Dogs were submitted to hermorrhagic shock, resuscitated shock and resuscitated shock plus a pulmonary bacterial insult. Pulmonary familure was absent in dogs submitted only to shock or to shock and its resuscitation. The addition of usually sub-lethal amounts of micro-organisms to the shock-resuscitated lung caused rapid death from pulmonary failure. Pulmonary failure was demonstrated by increased lung weight, hypoxemia, decreased compliance and a hemorrhagic destruction of lung tissue. These findings strongly support recent concepts of an infective genesis of \"shock lung\" in man."}
{"id": "PMID:240330", "title": "The use of Forane anesthesia for surface-induced deep hypothermia.", "content": "The effects of Forane anesthesia for deep surface hypothermia with 30 minutes of total circulatory occlusion were evaluated. With 100% O2 6 of 7 dogs developed motor disorders postoperatively, while 3 of 5 with 98% O2/2% CO2 and none with 95% O2/5% CO2 developed motor disorders. Cooling was uneventful except for 1 episode of ventricular fibrillation in the 5% CO2 group at 23 degrees C. Resuscitation was easy, but the early rewarming period was characterized by repeated episodes of ventricular fibrillation and delayed recovery of cardiac function, especially in the 100% O2 group. Blood lactate levels remained low during cooling and gradually increased during rewarming in all groups, with the highest levels in the 100% O2 group and the lowest in the 5% CO2 group. It is concluded that Forane can be used for surface hypothermia with 30 minutes' circulatory occlusion when administered in 95% O2/5% CO2. A Comparison of these results with previously reported series indicates that Forane is inferior to ether but may be superior to halothane for surface hypothermia.", "contents": "The use of Forane anesthesia for surface-induced deep hypothermia. The effects of Forane anesthesia for deep surface hypothermia with 30 minutes of total circulatory occlusion were evaluated. With 100% O2 6 of 7 dogs developed motor disorders postoperatively, while 3 of 5 with 98% O2/2% CO2 and none with 95% O2/5% CO2 developed motor disorders. Cooling was uneventful except for 1 episode of ventricular fibrillation in the 5% CO2 group at 23 degrees C. Resuscitation was easy, but the early rewarming period was characterized by repeated episodes of ventricular fibrillation and delayed recovery of cardiac function, especially in the 100% O2 group. Blood lactate levels remained low during cooling and gradually increased during rewarming in all groups, with the highest levels in the 100% O2 group and the lowest in the 5% CO2 group. It is concluded that Forane can be used for surface hypothermia with 30 minutes' circulatory occlusion when administered in 95% O2/5% CO2. A Comparison of these results with previously reported series indicates that Forane is inferior to ether but may be superior to halothane for surface hypothermia."}
{"id": "PMID:240331", "title": "A critical study on RO-4-1284 antagonism in mice.", "content": "Ro-4-1284 is found to produce ptosis, hypothermia, sedation and miosis in mice, and the antagonsim to these symptoms is investigated. The study reports the differential effects of various pharmacologically distinct classes of compounds. The relevance of this type of experiments to possible antidepressant drug activity is discussed.", "contents": "A critical study on RO-4-1284 antagonism in mice. Ro-4-1284 is found to produce ptosis, hypothermia, sedation and miosis in mice, and the antagonsim to these symptoms is investigated. The study reports the differential effects of various pharmacologically distinct classes of compounds. The relevance of this type of experiments to possible antidepressant drug activity is discussed."}
{"id": "PMID:240332", "title": "Effects of chlordiazepoxide, CNS stimulants and their combinations on avoidance behaviour in mice.", "content": "Various central stimulant drugs were tested in mice subjected to five daily 100-trial avoidance sessions in the shuttle-box. Facilitation of avoidance responding was observed following i.p. administration of metamphetamine and cocaine, but not following methlyphenidate, caffeine, pentetrazole and strychnine. Some favourable effects were obtained by combining the above stimulant drugs with cholrdiazepoxide. Advantages in the combination with chlordiazepoxide were particularly evident in the case of methamphetamine.", "contents": "Effects of chlordiazepoxide, CNS stimulants and their combinations on avoidance behaviour in mice. Various central stimulant drugs were tested in mice subjected to five daily 100-trial avoidance sessions in the shuttle-box. Facilitation of avoidance responding was observed following i.p. administration of metamphetamine and cocaine, but not following methlyphenidate, caffeine, pentetrazole and strychnine. Some favourable effects were obtained by combining the above stimulant drugs with cholrdiazepoxide. Advantages in the combination with chlordiazepoxide were particularly evident in the case of methamphetamine."}
{"id": "PMID:240333", "title": "[Age dependence and stimulation of renal excretion of trishydroxymethylaminomethane (Tham)].", "content": "In rats of different age (5 to 240 days old) the renal excretion of Trishydroxymethylaminomethane (THAM) was studied. In 5 and in 240 days old rats the renal excretion of THAM was slower than in rats of other age groups. Stimulation of diuresis by i.p. injection of mannitol, thiazide or by oral water load resulted in an increase in THAM excretion in 5 and in 240 days old rats. The renal excretion of THAM was also increased by repeated administration of THAM in all age groups, except in new born rats. Possible mechanisms of action are discussed.", "contents": "[Age dependence and stimulation of renal excretion of trishydroxymethylaminomethane (Tham)]. In rats of different age (5 to 240 days old) the renal excretion of Trishydroxymethylaminomethane (THAM) was studied. In 5 and in 240 days old rats the renal excretion of THAM was slower than in rats of other age groups. Stimulation of diuresis by i.p. injection of mannitol, thiazide or by oral water load resulted in an increase in THAM excretion in 5 and in 240 days old rats. The renal excretion of THAM was also increased by repeated administration of THAM in all age groups, except in new born rats. Possible mechanisms of action are discussed."}
{"id": "PMID:240334", "title": "Should tonometry screening be done by technicians instead of physicians?", "content": "A random sample of 768 clinic patients 40 years or older were screened by a technician utilizing Schlotz tonometry. All patients with an intraocular pressure of 20 mm Hg or more were referred for ophthalmological evaluation. The prevalence of frank glaucoma and suspected glaucoma in this infirm population was 1.8% and 2.5%, respectively. The cost of detecting frank or suspected glaucoma decreased in the second half of the study due to a decrease in the number of false-positive tests. These findings suggest that all clinic patients 40 years or older should be screened for glaucoma. Because many internists are reluctant to screen for glaucoma and because there are large number of false-positive tests by those who do tonometry episodically, we suggest that technicians do glaucoma screening.", "contents": "Should tonometry screening be done by technicians instead of physicians? A random sample of 768 clinic patients 40 years or older were screened by a technician utilizing Schlotz tonometry. All patients with an intraocular pressure of 20 mm Hg or more were referred for ophthalmological evaluation. The prevalence of frank glaucoma and suspected glaucoma in this infirm population was 1.8% and 2.5%, respectively. The cost of detecting frank or suspected glaucoma decreased in the second half of the study due to a decrease in the number of false-positive tests. These findings suggest that all clinic patients 40 years or older should be screened for glaucoma. Because many internists are reluctant to screen for glaucoma and because there are large number of false-positive tests by those who do tonometry episodically, we suggest that technicians do glaucoma screening."}
{"id": "PMID:240335", "title": "[Kinetics of the proteolytic activity of intact human spermatozoa].", "content": "Seminal plasma free intact human washed spermatozoa have hydrolytic activity on N-benzoil-D-L-arginine-naftilamide (BANA). Kinetic activities of this enzymatic activity are similar to those described for acrosine. Therefore, it is likely that it would be the same enzyme. BANA- hydrolytic activity might be liberated to the medium by incubation of pH lower than 4.0 and reincorporates to the membrane after adjustment of the medium to alkaline pH. pH- dependant enzyme liberation curve is similar to titration curve of sialic acid attached to the membrane. Attachment of the enzyme to the spermatic membrane diminishes its specific activity. However, if spermatozoa are previously treated with neuraminidase, its membrane afinity is inhibited. It is thought that this enzyme in the spermatozoon is present as protein ionically bound to the membrane and that sialic acid participates in this union. It is postulated that drastic treatments such as the use of ultrasound or detergents produce redistribution of specific proteins.", "contents": "[Kinetics of the proteolytic activity of intact human spermatozoa]. Seminal plasma free intact human washed spermatozoa have hydrolytic activity on N-benzoil-D-L-arginine-naftilamide (BANA). Kinetic activities of this enzymatic activity are similar to those described for acrosine. Therefore, it is likely that it would be the same enzyme. BANA- hydrolytic activity might be liberated to the medium by incubation of pH lower than 4.0 and reincorporates to the membrane after adjustment of the medium to alkaline pH. pH- dependant enzyme liberation curve is similar to titration curve of sialic acid attached to the membrane. Attachment of the enzyme to the spermatic membrane diminishes its specific activity. However, if spermatozoa are previously treated with neuraminidase, its membrane afinity is inhibited. It is thought that this enzyme in the spermatozoon is present as protein ionically bound to the membrane and that sialic acid participates in this union. It is postulated that drastic treatments such as the use of ultrasound or detergents produce redistribution of specific proteins."}
{"id": "PMID:240336", "title": "Kinetics and properties of beta-ketothiolase from Clostridium pasteurianum.", "content": "1. Beta-Ketothiolase of Clostridium pasteurianum was purified 130-fold by ammonium sulphate fractionation and by column chromatography using DEAE-Sephadex A-50 and hydroxylapatite. Subjected to gel electrophoresis beta-ketothiolase revealed two distinct bands; by isoelectric focusing two enzymes with isoelectric points at pH 4.5 and 7.6 were separated. As established by sucrose density gradient centrifugation the molecular weight of both enzymes was found to be 158000. 2. The condensation reaction was measured by a coupled optical test using beta-hydroxybutyryl-CoA dehydrogenase as auxiliary enzyme and either acetyl-CoA or free coenzyme A plus acetyl-phosphate and phosphotransacetylase (regenerating system) or acetyl-CoA plus regenerating system as substrates. Beta-Ketothiolase from C. pasteurianum used only 20% of the chemically synthesized acetyl-CoA; the enzyme from Alcaligenes eutrophus H 16 used 25%. When the regenerating system was added the condensation reaction continued. The enzyme from C. pasteurianum was inactivated by free coenzyme A, while the enzyme from A. eutrophus was inhibited. When acetyl-CoA was added as the substrate the initial velocity determination was impeded by the lack of linearity. With acetyl-CoA as the substrate the Km-value was found to be 2.5 mM acetyl-CoA. If free CoASH (or acetyl-CoA) plus regenerating system was added the Km was 0.44 mM (0.42 mM) acetyl-CoA. 3. The beta-ketothiolase activity was measured in the direction of acetoacetyl-CoA cleavage by an optical assay following the decrease of the enol and chelate form of acetoacetyl-CoA by absorption measurement at 305 nm. The activity was maximal at 24 nM MgCl2. The apparent Km values for acetoacetyl-CoA were 0.133 mM and 0.105 mM with 0.065 and 0.016 mM CoASH, respectively. The Km-values as calculated for only the keto form of acetoacetyl-CoA were 0.0471 and 0.0372 mM, respectively. The cleavage reaction was inhibited by high acetoacetyl-CoA concentrations; the inihibition was partially relieved by CoASH. In the range of low concentrations of acetoacetyl-CoA only a slight inhibition by CoASH was observed. The Km for CoASH was found to be 0.0288 and 0.0189 mM with 0.09 and 0.045 mM acetoacetyl-CoA, respectively. High concentrations of CoASH exerted an inhibitory effect on the cleavage reaction. With respect to enzyme kinetics and sensitivity to inhibitors and metabolites the beta-ketothiolases of C. pasteurianum and A. eutrophus were rather similar.", "contents": "Kinetics and properties of beta-ketothiolase from Clostridium pasteurianum. 1. Beta-Ketothiolase of Clostridium pasteurianum was purified 130-fold by ammonium sulphate fractionation and by column chromatography using DEAE-Sephadex A-50 and hydroxylapatite. Subjected to gel electrophoresis beta-ketothiolase revealed two distinct bands; by isoelectric focusing two enzymes with isoelectric points at pH 4.5 and 7.6 were separated. As established by sucrose density gradient centrifugation the molecular weight of both enzymes was found to be 158000. 2. The condensation reaction was measured by a coupled optical test using beta-hydroxybutyryl-CoA dehydrogenase as auxiliary enzyme and either acetyl-CoA or free coenzyme A plus acetyl-phosphate and phosphotransacetylase (regenerating system) or acetyl-CoA plus regenerating system as substrates. Beta-Ketothiolase from C. pasteurianum used only 20% of the chemically synthesized acetyl-CoA; the enzyme from Alcaligenes eutrophus H 16 used 25%. When the regenerating system was added the condensation reaction continued. The enzyme from C. pasteurianum was inactivated by free coenzyme A, while the enzyme from A. eutrophus was inhibited. When acetyl-CoA was added as the substrate the initial velocity determination was impeded by the lack of linearity. With acetyl-CoA as the substrate the Km-value was found to be 2.5 mM acetyl-CoA. If free CoASH (or acetyl-CoA) plus regenerating system was added the Km was 0.44 mM (0.42 mM) acetyl-CoA. 3. The beta-ketothiolase activity was measured in the direction of acetoacetyl-CoA cleavage by an optical assay following the decrease of the enol and chelate form of acetoacetyl-CoA by absorption measurement at 305 nm. The activity was maximal at 24 nM MgCl2. The apparent Km values for acetoacetyl-CoA were 0.133 mM and 0.105 mM with 0.065 and 0.016 mM CoASH, respectively. The Km-values as calculated for only the keto form of acetoacetyl-CoA were 0.0471 and 0.0372 mM, respectively. The cleavage reaction was inhibited by high acetoacetyl-CoA concentrations; the inihibition was partially relieved by CoASH. In the range of low concentrations of acetoacetyl-CoA only a slight inhibition by CoASH was observed. The Km for CoASH was found to be 0.0288 and 0.0189 mM with 0.09 and 0.045 mM acetoacetyl-CoA, respectively. High concentrations of CoASH exerted an inhibitory effect on the cleavage reaction. With respect to enzyme kinetics and sensitivity to inhibitors and metabolites the beta-ketothiolases of C. pasteurianum and A. eutrophus were rather similar."}
{"id": "PMID:240337", "title": "[Neurologic manifestations following pertussis vaccination].", "content": "Twenty cases of acute neurological complications occuring within 7 days of pertussis immunization are reported. Convulsions were present in every case and status epilepticus was observed in five infants. In only 4 cases were neurological or epileptic sequelae lacking. The clustering of neurological complications in the 24 hours following immunization is not consistent with the hypothesis of a mere temporal coincidence. However, the mechanism and incidence of post-immunization encephalopathies remains obscure and epidemiological studies are in order.", "contents": "[Neurologic manifestations following pertussis vaccination]. Twenty cases of acute neurological complications occuring within 7 days of pertussis immunization are reported. Convulsions were present in every case and status epilepticus was observed in five infants. In only 4 cases were neurological or epileptic sequelae lacking. The clustering of neurological complications in the 24 hours following immunization is not consistent with the hypothesis of a mere temporal coincidence. However, the mechanism and incidence of post-immunization encephalopathies remains obscure and epidemiological studies are in order."}
{"id": "PMID:240343", "title": "Malakoplakia. Defect in digestion of phagocytized material due to impaired vacuolar acidification?", "content": "On the basis of light and electron microscopical findings in a case of malakoplakia of urinary bladder, (1) we concur with others that malakoplakia is a hyperplastic accumulation of histiocytes, and that the formation of Michaelis-Gutmann bodies is associated with incomplete digestion of phagocytized cell debris; (2) we hypothesize that digestion within phagolysosomes is impaired because of deficient acidification; and (3) we suggest that the defect in acidification in some cases may be related to treatment with drugs that affect the mechanism of phagocytic vacuolar acidification.", "contents": "Malakoplakia. Defect in digestion of phagocytized material due to impaired vacuolar acidification? On the basis of light and electron microscopical findings in a case of malakoplakia of urinary bladder, (1) we concur with others that malakoplakia is a hyperplastic accumulation of histiocytes, and that the formation of Michaelis-Gutmann bodies is associated with incomplete digestion of phagocytized cell debris; (2) we hypothesize that digestion within phagolysosomes is impaired because of deficient acidification; and (3) we suggest that the defect in acidification in some cases may be related to treatment with drugs that affect the mechanism of phagocytic vacuolar acidification."}
{"id": "PMID:240345", "title": "Replantation of avulsed teeth. A review.", "content": "Time is a critical factor in successful replantation. The avulsed tooth is simply washed and replaced immediately. Where contamination with soil occurs anti-tetanus prophylaxis is given and some form of splinting is necessary for 3-4 weeks. Endodontic therapy is performed prior to replacement if there is a delay of more than two hours and where apex formation is complete it should be commenced within 10 days. Calcium hydroxide is useful as a root canal dressing and in controlling resorption. The value of immediate replacement and treatment should be publicised.", "contents": "Replantation of avulsed teeth. A review. Time is a critical factor in successful replantation. The avulsed tooth is simply washed and replaced immediately. Where contamination with soil occurs anti-tetanus prophylaxis is given and some form of splinting is necessary for 3-4 weeks. Endodontic therapy is performed prior to replacement if there is a delay of more than two hours and where apex formation is complete it should be commenced within 10 days. Calcium hydroxide is useful as a root canal dressing and in controlling resorption. The value of immediate replacement and treatment should be publicised."}
{"id": "PMID:240346", "title": "Resolution of proteases in the keratinolytic larvae of the webbing clothes moth.", "content": "The proteases of the larvae of the webbing clothes moth, Tineola bisselliella, were investigated because of this organism's phylogenetic rank as a member of the lower invertebrates, its unique position as one of the relatively few organisms that can digest keratin and its importance as a serious fabric pest. Both the number and nature of different proteolytic enzymes present were investigated and the various activities partially fractionated by ammonium sulphate precipitation and chromatography on DEAE-cellulose and Sephadex G200 columns. A complex mixture of peptidases and proteinases has been found in extracts of whole larvae and has been shown to be associated with the larval digestive tract. The proteinases include metal-chelator-sensitive proteinases (metalloproteinases) and serine proteinases but no SH-proteinases or acid proteinases. The serine proteinases include both trypsin-like and chymotrypsin-like activities. Four major and three minor anionic trypsin-like enzymes and a single major cationic trypsin-like enzyme have been detected. Only a single anionic chymotrypsin-like enzyme appears to be present. The trypsin-like enzymes are unaffected by the naturally occurring proteinase inhibitors, chicken ovomucoid, soybean trypsin inhibitor and lima bean trypsin inhibitor, while the chymotrypsin-like enzyme is inhibited by soybean trypsin inhibitor only. The enzymes resemble the serine proteinases from microorganisms in their pH stability. The peptidases include both aminopeptidase and carboxypeptidase activities and both are present in multiple forms. Sixteen aminopeptidase bands have been detected and all are present in individual larvae. They are not inhibited completely by reagents specific for any of the common active sites, and have different specificity requirements. Two carboxypeptidases have been detected on acrylamide gels and have been completely separated on DEAE-cellulose. No evidence could be found for the existence of any of these proteases as inactive precursors.", "contents": "Resolution of proteases in the keratinolytic larvae of the webbing clothes moth. The proteases of the larvae of the webbing clothes moth, Tineola bisselliella, were investigated because of this organism's phylogenetic rank as a member of the lower invertebrates, its unique position as one of the relatively few organisms that can digest keratin and its importance as a serious fabric pest. Both the number and nature of different proteolytic enzymes present were investigated and the various activities partially fractionated by ammonium sulphate precipitation and chromatography on DEAE-cellulose and Sephadex G200 columns. A complex mixture of peptidases and proteinases has been found in extracts of whole larvae and has been shown to be associated with the larval digestive tract. The proteinases include metal-chelator-sensitive proteinases (metalloproteinases) and serine proteinases but no SH-proteinases or acid proteinases. The serine proteinases include both trypsin-like and chymotrypsin-like activities. Four major and three minor anionic trypsin-like enzymes and a single major cationic trypsin-like enzyme have been detected. Only a single anionic chymotrypsin-like enzyme appears to be present. The trypsin-like enzymes are unaffected by the naturally occurring proteinase inhibitors, chicken ovomucoid, soybean trypsin inhibitor and lima bean trypsin inhibitor, while the chymotrypsin-like enzyme is inhibited by soybean trypsin inhibitor only. The enzymes resemble the serine proteinases from microorganisms in their pH stability. The peptidases include both aminopeptidase and carboxypeptidase activities and both are present in multiple forms. Sixteen aminopeptidase bands have been detected and all are present in individual larvae. They are not inhibited completely by reagents specific for any of the common active sites, and have different specificity requirements. Two carboxypeptidases have been detected on acrylamide gels and have been completely separated on DEAE-cellulose. No evidence could be found for the existence of any of these proteases as inactive precursors."}
{"id": "PMID:240347", "title": "The rectal administration of lactulose.", "content": "A lactulose colonic washout (pH 4.5) was administered to six male patients with portal systemic encephalopathy.  Estimation of blood ammonia levels and electroencephalography were performed before and after each treatment.  Five patients recorded a significant fall in blood ammonia level as a result of lactulose therapy (P less than .025).  In the sixth subject, an enema with buffered physiological saline, pH 4.5, induced a fall in ammonia which was not increased by subsequent lactulose solution. Improvement in the electroencephalogram was recorded in all periods where a lactulose colonic washout produced a  fall in blood ammonia level.", "contents": "The rectal administration of lactulose. A lactulose colonic washout (pH 4.5) was administered to six male patients with portal systemic encephalopathy.  Estimation of blood ammonia levels and electroencephalography were performed before and after each treatment.  Five patients recorded a significant fall in blood ammonia level as a result of lactulose therapy (P less than .025).  In the sixth subject, an enema with buffered physiological saline, pH 4.5, induced a fall in ammonia which was not increased by subsequent lactulose solution. Improvement in the electroencephalogram was recorded in all periods where a lactulose colonic washout produced a  fall in blood ammonia level."}
{"id": "PMID:240349", "title": "Volatile organic components in the Skylab 4 spacecraft atmosphere.", "content": "The volatile organic components in the spacecraft cabin atmosphere of Skylab 4 were trapped on a solid adsorbent at various times during the mission. In post-flight analyses, more than 300 compounds in concentrations from less than 1 ppb up to 8000 ppb could be detected by high-resolution gas chromatography. In the samples of the 11th, 47th, and 77th day of the mission, approximately 100 components in the molecular weight range of 58 to 592 were identified by mass spectrometry. Besides components known from other environments, such as alkanes, alkenes, and alkylated aromatic hydrocarbons, components typical for the human metabolism such as ketones and alcohols were found. Other typical components in the spacecraft atmosphere are fluorocarbons (freons) and various silicone compounds, mostly normal and cyclic methylsiloxanes.", "contents": "Volatile organic components in the Skylab 4 spacecraft atmosphere. The volatile organic components in the spacecraft cabin atmosphere of Skylab 4 were trapped on a solid adsorbent at various times during the mission. In post-flight analyses, more than 300 compounds in concentrations from less than 1 ppb up to 8000 ppb could be detected by high-resolution gas chromatography. In the samples of the 11th, 47th, and 77th day of the mission, approximately 100 components in the molecular weight range of 58 to 592 were identified by mass spectrometry. Besides components known from other environments, such as alkanes, alkenes, and alkylated aromatic hydrocarbons, components typical for the human metabolism such as ketones and alcohols were found. Other typical components in the spacecraft atmosphere are fluorocarbons (freons) and various silicone compounds, mostly normal and cyclic methylsiloxanes."}
{"id": "PMID:240353", "title": "Autoaggressive reactions and leukemia virus infections: interrelated events in their pathogenesis.", "content": "Leukemia viruses can be activated from within murine hosts by immunological reactions against foreign histocompatibility antigens both during graft versus host reactions (GVHR) and host versus graft reactions (HVGR). Presence of both lymphocyte-mediated graft rejection reactions and immuno suppression appears necessary for maximal virus activation and replication in vitro, although viruses can be activated by mixed lymphocyte reactions (MLR) alone in vitro. During HVGR, viruses are first detectable in lymph nodes draining the graft site, and later reach maximal titers in the spleen. Mice infected with murine leukemia virus (MuLV) as neonates or carrying MuLV secondary to milk transmission (carriers) also develop complex autoaggressive responses. By a sensitive in vitro microcytotoxicity assay, neoplastic or pre-neoplastic thymocytes from carrier mice were found to react vigorously against normal uninfected syngeneic embryonic fibroblasts, whereas they reacted much less vigorously with similarly prepared but MuLV-infected fibroblasts. Thymocytes from uninfected animals did not react with infected or uninfected fibroblasts. Peripheral lymphocytes from carriers reacted against MuLV infected fibroblasts, but not against uninfected fibroblasts, a pattern indistinguishable from deliberately-immunized mice. It is proposed that responses analogous to GVHR are also important in the pathogenesis of leukemia following exogenous leukemia virus infection.", "contents": "Autoaggressive reactions and leukemia virus infections: interrelated events in their pathogenesis. Leukemia viruses can be activated from within murine hosts by immunological reactions against foreign histocompatibility antigens both during graft versus host reactions (GVHR) and host versus graft reactions (HVGR). Presence of both lymphocyte-mediated graft rejection reactions and immuno suppression appears necessary for maximal virus activation and replication in vitro, although viruses can be activated by mixed lymphocyte reactions (MLR) alone in vitro. During HVGR, viruses are first detectable in lymph nodes draining the graft site, and later reach maximal titers in the spleen. Mice infected with murine leukemia virus (MuLV) as neonates or carrying MuLV secondary to milk transmission (carriers) also develop complex autoaggressive responses. By a sensitive in vitro microcytotoxicity assay, neoplastic or pre-neoplastic thymocytes from carrier mice were found to react vigorously against normal uninfected syngeneic embryonic fibroblasts, whereas they reacted much less vigorously with similarly prepared but MuLV-infected fibroblasts. Thymocytes from uninfected animals did not react with infected or uninfected fibroblasts. Peripheral lymphocytes from carriers reacted against MuLV infected fibroblasts, but not against uninfected fibroblasts, a pattern indistinguishable from deliberately-immunized mice. It is proposed that responses analogous to GVHR are also important in the pathogenesis of leukemia following exogenous leukemia virus infection."}
{"id": "PMID:240366", "title": "[Interactions of some parasympatholytics and structurally similar drugs with bovine serum albumin].", "content": "The interactions of the parasympatholytic drugs adiphenin, adiphenin H and propanthelin and the structurally related compounds, diphenhydramine, D-propoxyphene and methadone with bovine serum albumin (BSA) are studied by equilibrium dialysis and ultracentrifugation. The results show that BSA has a few binding sites (n less than 10) for the mentioned drugs. The association between the compounds under study and BSA are relatively weak. The binding constants are in the range of 10(3) l/Mol.", "contents": "[Interactions of some parasympatholytics and structurally similar drugs with bovine serum albumin]. The interactions of the parasympatholytic drugs adiphenin, adiphenin H and propanthelin and the structurally related compounds, diphenhydramine, D-propoxyphene and methadone with bovine serum albumin (BSA) are studied by equilibrium dialysis and ultracentrifugation. The results show that BSA has a few binding sites (n less than 10) for the mentioned drugs. The association between the compounds under study and BSA are relatively weak. The binding constants are in the range of 10(3) l/Mol."}
{"id": "PMID:240367", "title": "[Pharmacokinetic aspects of tumor tissue impairment by cancerostatics. Ways for the intensification of the induced attack in the multiple step cancer therapy. CMT-Selectine].", "content": "After discussion of the causes of natural selectivity of cancerostatics it is pointed out that, thanks to recent advances in cell kinetics (cycle-adequate selection of cancerostatics) combined with microtopography of substrate supply in the intercapillary region of cancer tissue, chemotherapeutic treatment of cancer is developing into a theoretically founded and modifiable therapy. Within the nexus of closely related problems it is especially the studies on pharmacokinetics of cancerostatics that still are in arreals. The discussed course of such an investigation basis oe the carticularly of cancer tissue, i.e., the often inadequate vascularization parameters that deteriorate even further with growing tumor size. -- The given valance equation for a change in the concentration of a cancerostatic in tumor tissue has been evaluated using, for an example, a substance from the alkylating group whose mass number approximately coindices with that of cyclophosphamide in its active form. As far as the better vascularized cancer tissue farther from the capillaries are concerned (e.g. early stages of tumors and metastases) the effective dose only drops from 1 to about 0.7. In poorly vacularized cancer tissue, on the other hand, the respective effective dose is reduced from 1 to approx. 0.25. Unfortunately, however, this drop in effective dose takes place exactly in a location where the most resistant fractions of tumor cells are to be found. A feasible way out this crucial dilemma inherent in the chemotherapy of cancer is to combine a substance of low mass numer that causes a pronounced long-term stimulation of body own defence (e.g. our BA 1, and N-(2-cyanoethylene)-urea) with a cancerostatic like CMT-selectine that -- in optimally hyperacidified cancer tissues -- reaches its active form only at a reduced pH so that (contrary to normal cancerostatics) stimulation of the body-own defence caused by the first mentioned substance is not impaired.", "contents": "[Pharmacokinetic aspects of tumor tissue impairment by cancerostatics. Ways for the intensification of the induced attack in the multiple step cancer therapy. CMT-Selectine]. After discussion of the causes of natural selectivity of cancerostatics it is pointed out that, thanks to recent advances in cell kinetics (cycle-adequate selection of cancerostatics) combined with microtopography of substrate supply in the intercapillary region of cancer tissue, chemotherapeutic treatment of cancer is developing into a theoretically founded and modifiable therapy. Within the nexus of closely related problems it is especially the studies on pharmacokinetics of cancerostatics that still are in arreals. The discussed course of such an investigation basis oe the carticularly of cancer tissue, i.e., the often inadequate vascularization parameters that deteriorate even further with growing tumor size. -- The given valance equation for a change in the concentration of a cancerostatic in tumor tissue has been evaluated using, for an example, a substance from the alkylating group whose mass number approximately coindices with that of cyclophosphamide in its active form. As far as the better vascularized cancer tissue farther from the capillaries are concerned (e.g. early stages of tumors and metastases) the effective dose only drops from 1 to about 0.7. In poorly vacularized cancer tissue, on the other hand, the respective effective dose is reduced from 1 to approx. 0.25. Unfortunately, however, this drop in effective dose takes place exactly in a location where the most resistant fractions of tumor cells are to be found. A feasible way out this crucial dilemma inherent in the chemotherapy of cancer is to combine a substance of low mass numer that causes a pronounced long-term stimulation of body own defence (e.g. our BA 1, and N-(2-cyanoethylene)-urea) with a cancerostatic like CMT-selectine that -- in optimally hyperacidified cancer tissues -- reaches its active form only at a reduced pH so that (contrary to normal cancerostatics) stimulation of the body-own defence caused by the first mentioned substance is not impaired."}
{"id": "PMID:240368", "title": "[Blood circulation, oxygen pressure and pH of the cerebral cortex under the influence of bencyclane].", "content": "The effect of N-[3-(1-benzyl-cycloheptyl-oxy)-propyl]-N,N-dimethyl-amine (bencyclan-hydrogenfumarate, Fludilat\u00bf on the cerebral vascular system was studied by means of the following methods: 1. In pigs regional cerebral cortical blood flow was continuously recorded with a heat conduction device, cortical pH with a glass electode in which the flat measuring surface and the reference were close together. Cortical pO2 was recorded with a multiwire platinum electrode. Systemic arterial blood pressure was monitored by means of a Statham transducer. 2. In a second series in cats the perivascular space of small pial arteries or arterioles was perfused with cerebro-spinal fluid (CSF) to which bencyclan had been added. The perfusion was performed by means of micropipettes. Local cortical blood flow increased slightly for some minutes after slow infusion of 1--3 mg/kg bencyclan. Rapid injection caused initially a significant decrease in arterial blood pressure, which was accompanied by a transient decrease in CBF and in cortical pH. After the return of the arterial blood pressure to its initial value, CBF increased. Cortical pO2 and cortical pH returned to initial values. After slow infusion of the substance the pH variation was usually very slight or it was missed completely. Perivascular microperfusion wtih CSF containing bencyclan caused dilatation of those pial sections which were in contact with the drug. High concentration of the drug caused stronger dilatations than did low concentrations. It is concluded that the substance causes dilatations of the cerebral vessels and that this dilatation occurs also during constant perivascular pH.", "contents": "[Blood circulation, oxygen pressure and pH of the cerebral cortex under the influence of bencyclane]. The effect of N-[3-(1-benzyl-cycloheptyl-oxy)-propyl]-N,N-dimethyl-amine (bencyclan-hydrogenfumarate, Fludilat\u00bf on the cerebral vascular system was studied by means of the following methods: 1. In pigs regional cerebral cortical blood flow was continuously recorded with a heat conduction device, cortical pH with a glass electode in which the flat measuring surface and the reference were close together. Cortical pO2 was recorded with a multiwire platinum electrode. Systemic arterial blood pressure was monitored by means of a Statham transducer. 2. In a second series in cats the perivascular space of small pial arteries or arterioles was perfused with cerebro-spinal fluid (CSF) to which bencyclan had been added. The perfusion was performed by means of micropipettes. Local cortical blood flow increased slightly for some minutes after slow infusion of 1--3 mg/kg bencyclan. Rapid injection caused initially a significant decrease in arterial blood pressure, which was accompanied by a transient decrease in CBF and in cortical pH. After the return of the arterial blood pressure to its initial value, CBF increased. Cortical pO2 and cortical pH returned to initial values. After slow infusion of the substance the pH variation was usually very slight or it was missed completely. Perivascular microperfusion wtih CSF containing bencyclan caused dilatation of those pial sections which were in contact with the drug. High concentration of the drug caused stronger dilatations than did low concentrations. It is concluded that the substance causes dilatations of the cerebral vessels and that this dilatation occurs also during constant perivascular pH."}
{"id": "PMID:240369", "title": "Toxicological and pharmacological investigations of pinazepam (7-chloro-1-propargyl-5-phenyl-3H-1,4-benzodiazepin-2-one): a new psychotherapeutic agent.", "content": "The pharmacological and toxicological properties of 7-chloro-1-propargyl-5-phenyl-3H-1,4-benzodiazepin-2-one (pinazepam) were investigated and compared with those of diazepam. In mouse and rat acute toxicity, in rat motor coordination and in rat metrazol convulsion tests pinazepam was compared with oxazepam too. Pinazepam, which is characterized by the presence of a propargylic side chain, showed a lower toxicity, hypnotic activity and muscular-relaxant activity than diazepam. Pinazepam and diazepam showed, however, similar activity in reducing aggressive behaviour in mice, stimulating the exploratory behaviour in rats and in potentiating hexobarbital narcosis. No clear-cut differences were observed in the anticonvulsant properties of the two drugs when tested against metrazol, strychnine and electroshock induced seizures. Pinazepam differs from diazepam for its longer duration of action. The main metabolic product found in the urine of rats and dogs treated with pinazepam was oxazepam.", "contents": "Toxicological and pharmacological investigations of pinazepam (7-chloro-1-propargyl-5-phenyl-3H-1,4-benzodiazepin-2-one): a new psychotherapeutic agent. The pharmacological and toxicological properties of 7-chloro-1-propargyl-5-phenyl-3H-1,4-benzodiazepin-2-one (pinazepam) were investigated and compared with those of diazepam. In mouse and rat acute toxicity, in rat motor coordination and in rat metrazol convulsion tests pinazepam was compared with oxazepam too. Pinazepam, which is characterized by the presence of a propargylic side chain, showed a lower toxicity, hypnotic activity and muscular-relaxant activity than diazepam. Pinazepam and diazepam showed, however, similar activity in reducing aggressive behaviour in mice, stimulating the exploratory behaviour in rats and in potentiating hexobarbital narcosis. No clear-cut differences were observed in the anticonvulsant properties of the two drugs when tested against metrazol, strychnine and electroshock induced seizures. Pinazepam differs from diazepam for its longer duration of action. The main metabolic product found in the urine of rats and dogs treated with pinazepam was oxazepam."}
{"id": "PMID:240370", "title": "The history of controlled hypotension.", "content": "As the physiology of deliberate hypotension has been unravelled, and as each new pharmacological agent has become available which either depresses or blocks peripheral vascular tone, depresses myocardial performance, or interferes with the conducting tissues within the myocardium, its possible incorporation into the armamentarium of the anaesthetist who offers induced hypotension has been considered. The result has been a sequence of variations in technique of characteristically recognizable vintage. No matter how the condition of induced hypotension is produced, there is usually vasodilatation, and the characteristic disturbance in physiology is of a loss of postural reactivity in the cardiovascular system. Important lessons have been learned concerning the management of shock states. Though it is difficult to evaluate the morbidity of deliberate induced hypotension, and terms such as \"physiological trespass\" have been used by its antagonists, it would appear that a well-considered and skilfully managed controlled hypotension is no more of a physiological trespass than anaesthesia, nor indeed than the trespass of the surgeon's knife itself.", "contents": "The history of controlled hypotension. As the physiology of deliberate hypotension has been unravelled, and as each new pharmacological agent has become available which either depresses or blocks peripheral vascular tone, depresses myocardial performance, or interferes with the conducting tissues within the myocardium, its possible incorporation into the armamentarium of the anaesthetist who offers induced hypotension has been considered. The result has been a sequence of variations in technique of characteristically recognizable vintage. No matter how the condition of induced hypotension is produced, there is usually vasodilatation, and the characteristic disturbance in physiology is of a loss of postural reactivity in the cardiovascular system. Important lessons have been learned concerning the management of shock states. Though it is difficult to evaluate the morbidity of deliberate induced hypotension, and terms such as \"physiological trespass\" have been used by its antagonists, it would appear that a well-considered and skilfully managed controlled hypotension is no more of a physiological trespass than anaesthesia, nor indeed than the trespass of the surgeon's knife itself."}
{"id": "PMID:240374", "title": "An evaluation of Na+, C1- and pH ion-specific electrodes in the study of the electrolyte contents of epidermal transudate and sweat.", "content": "Ion-specific electrode detectors have been used to measure electrolytes in various biological fluids, including sweat. As part of a study of skin barrier function, we have used such electrodes to detect the presence of sodium, chloride and hydrogen (pH) in the transepidermal water loss. This paper describes the effects of cellophane tape stripping (of human forearm epidermis in vivo) on surface electrolyte concentrations, in parallel with observations on transepidermal water loss and galvanic skin resistance.", "contents": "An evaluation of Na+, C1- and pH ion-specific electrodes in the study of the electrolyte contents of epidermal transudate and sweat. Ion-specific electrode detectors have been used to measure electrolytes in various biological fluids, including sweat. As part of a study of skin barrier function, we have used such electrodes to detect the presence of sodium, chloride and hydrogen (pH) in the transepidermal water loss. This paper describes the effects of cellophane tape stripping (of human forearm epidermis in vivo) on surface electrolyte concentrations, in parallel with observations on transepidermal water loss and galvanic skin resistance."}
{"id": "PMID:240378", "title": "Ocular hypotensive effect of atenolol (Tenormin, I.C.I.). A new beta-adrenergic blocker.", "content": "Atenolol (Tenormin or I.C.I. 66082) is a new beta-adrenergic blocking drug, unique in being cardio-selective and in having no intrinsic sympathomimetic or membrane activity. In a controlled double-blind study, a single 50 mg oral dose produced a significant fall in ocular tension for about 7 hours in five patients with definite or suspected glaucoma. The average maximum fall was 35 per cent of the initial pressure; it occurred at 5 hours after oral ingestion. Accordingly neither intrinsic sympathomimetic nor membrane activity can account for all the ocular hypotensive effect of beta blockers in humans. The practical implications for treatment of glaucoma require longer-term investigations some of which are in progress.", "contents": "Ocular hypotensive effect of atenolol (Tenormin, I.C.I.). A new beta-adrenergic blocker. Atenolol (Tenormin or I.C.I. 66082) is a new beta-adrenergic blocking drug, unique in being cardio-selective and in having no intrinsic sympathomimetic or membrane activity. In a controlled double-blind study, a single 50 mg oral dose produced a significant fall in ocular tension for about 7 hours in five patients with definite or suspected glaucoma. The average maximum fall was 35 per cent of the initial pressure; it occurred at 5 hours after oral ingestion. Accordingly neither intrinsic sympathomimetic nor membrane activity can account for all the ocular hypotensive effect of beta blockers in humans. The practical implications for treatment of glaucoma require longer-term investigations some of which are in progress."}
{"id": "PMID:240379", "title": "Effects of dietary hydrochloric acid on voluntary food intake and metabolism of sheep in relation to the use of mineral acids as silage additives.", "content": "1. In Expt I, a pelleted grass-meal diet was supplemented with hydrochloric acid, added to the grass pellets before feeding, at five levels from 0 to 628 mmol/kg dry matter (DM). Each diet was offered ad lib. for 21 d to five sheep in a 5 x 5 Latin-square design. 2. Voluntary food intake decreased rectilinearly with increasing HCl supplementation (P less than 0.001), to 42% of the control value for sheep on the high-HCl diet. The decrease in food intake was related both to dietary pH and to the extent of metabolic acidosis induced by the HCl treatment. Although the pH of rumen fluid decreased slightly with increasing HCl supplementation, effects of the HCl treatment on volatile fatty acid concentrations in rumen fluid were not significant (P greater than 0.05). 3. In Expt 2, palatability and metabolic effects of dietary HCl were studied by comparing its effect when mixed into the pelleted grass meal before feeding, with and without a supplement of an equivalent amount of sodium bicarbonate given intraruminally, or when HCl was given intraruminally while the sheep consumed pelleted grass meal alone. Each of the three treatments was given at two levels of HCl, 280 and 560 mmol/kg DM. At each level of dietary HCl supplementation, the three treatments and the control diet (pelleted grass meal alone) were each given to four sheep, in a Latin-square design, for 11 d. 4. At the low level of supplementation, HCl, when mixed into the pelleted grass meal, reduced food intake by 17%, this effect was not altered by NaHCO3 supplementation, but when HCl was given intraruminally food intake was not reduced. At the high level of HCl supplementation, food intake was reduced by about 40% by each method of HCl supplementation; and NaHCO3 supplementation did not appreciably alter the effect of HCl on food intake, but prevented metabolic acidosis associated with the HCl treatments. Food intakes for the low-HCl treatments were significantly higher than those for the high-HCl treatments (P less than 0.01) and the level of dietary HCl x treatment interaction was also significant (P less than 0.01). DM digestibility, and the pH and volatile fatty acid concentrations of rumen fluid were not significantly affected by the different treatments. 5. It is concluded that at a low level of HCl supplementation the adverse effects of dietary HCl on voluntary food intake of sheep is determined by palatability associated with low dietary pH, whereas at a high level of HCl supplementation the effect is determined by palatability and by a metabolic response.", "contents": "Effects of dietary hydrochloric acid on voluntary food intake and metabolism of sheep in relation to the use of mineral acids as silage additives. 1. In Expt I, a pelleted grass-meal diet was supplemented with hydrochloric acid, added to the grass pellets before feeding, at five levels from 0 to 628 mmol/kg dry matter (DM). Each diet was offered ad lib. for 21 d to five sheep in a 5 x 5 Latin-square design. 2. Voluntary food intake decreased rectilinearly with increasing HCl supplementation (P less than 0.001), to 42% of the control value for sheep on the high-HCl diet. The decrease in food intake was related both to dietary pH and to the extent of metabolic acidosis induced by the HCl treatment. Although the pH of rumen fluid decreased slightly with increasing HCl supplementation, effects of the HCl treatment on volatile fatty acid concentrations in rumen fluid were not significant (P greater than 0.05). 3. In Expt 2, palatability and metabolic effects of dietary HCl were studied by comparing its effect when mixed into the pelleted grass meal before feeding, with and without a supplement of an equivalent amount of sodium bicarbonate given intraruminally, or when HCl was given intraruminally while the sheep consumed pelleted grass meal alone. Each of the three treatments was given at two levels of HCl, 280 and 560 mmol/kg DM. At each level of dietary HCl supplementation, the three treatments and the control diet (pelleted grass meal alone) were each given to four sheep, in a Latin-square design, for 11 d. 4. At the low level of supplementation, HCl, when mixed into the pelleted grass meal, reduced food intake by 17%, this effect was not altered by NaHCO3 supplementation, but when HCl was given intraruminally food intake was not reduced. At the high level of HCl supplementation, food intake was reduced by about 40% by each method of HCl supplementation; and NaHCO3 supplementation did not appreciably alter the effect of HCl on food intake, but prevented metabolic acidosis associated with the HCl treatments. Food intakes for the low-HCl treatments were significantly higher than those for the high-HCl treatments (P less than 0.01) and the level of dietary HCl x treatment interaction was also significant (P less than 0.01). DM digestibility, and the pH and volatile fatty acid concentrations of rumen fluid were not significantly affected by the different treatments. 5. It is concluded that at a low level of HCl supplementation the adverse effects of dietary HCl on voluntary food intake of sheep is determined by palatability associated with low dietary pH, whereas at a high level of HCl supplementation the effect is determined by palatability and by a metabolic response."}
{"id": "PMID:240380", "title": "A study of the effectiveness of calcined magnesite as a neutralizing agent for hydrochloric acid in the diet of sheep.", "content": "1. Five experimental diets were offered ad lib. for 21 d to five sheep in a 5 x 5 Latin-square design experiment as follows: pelleted grass meal alone (control); pelleted grass meal plus hydrochloric acid (470 mmol/kg dry matter (OM); pelleted grass meal plus 470 mmol HCl/kg DM and either an equivalent amount of calcined magnesite (MgO) (235 mmol/kg DM) or twice the amount (470 mmol MgO/kg DM); pelleted grass meal plus 470 mmol MgO/kg DM. 2. MgO supplementation partly prevented the reduction in food intake caused by HCl, being more effective at the low than at the high level. When fed alone, the high level of MgO had a slight adverse effect on food intake. 3. There was no significant treatment effect on either the pH or volatile fatty acid concentrations of rumen fluid. MgO supplementation was only slightly effective in preventing the metabolic acidosis caused by HCl supplementation, as indicated by blood and urine acid-base measurements. 4. With the MgO-supplemented diets, values for the faecal and urinary excretion of magnesium were approximately 70 and 10% respectively of Mg intake and were not significantly affected by HCl supplementation. For rumen fluid, the water-soluble Mg concentration as a percentage of the total Mg concentration was similar for each treatment, approximately 90%. For faeces, the corresponding value was also similar for each treatment, approximately 30%. 5. MgO supplementation altered the effect of dietary HCl on faecal calcium excretion and on the balance of Ca, but did not alter its effect on urinary Ca excretion. 6. It is concluded that the beneficial effect of MgO supplementation on the intake of the HCl-treated diet was related more to its influence on dietary pH than on conditions in the rumen or the acid-base balance of the sheep.", "contents": "A study of the effectiveness of calcined magnesite as a neutralizing agent for hydrochloric acid in the diet of sheep. 1. Five experimental diets were offered ad lib. for 21 d to five sheep in a 5 x 5 Latin-square design experiment as follows: pelleted grass meal alone (control); pelleted grass meal plus hydrochloric acid (470 mmol/kg dry matter (OM); pelleted grass meal plus 470 mmol HCl/kg DM and either an equivalent amount of calcined magnesite (MgO) (235 mmol/kg DM) or twice the amount (470 mmol MgO/kg DM); pelleted grass meal plus 470 mmol MgO/kg DM. 2. MgO supplementation partly prevented the reduction in food intake caused by HCl, being more effective at the low than at the high level. When fed alone, the high level of MgO had a slight adverse effect on food intake. 3. There was no significant treatment effect on either the pH or volatile fatty acid concentrations of rumen fluid. MgO supplementation was only slightly effective in preventing the metabolic acidosis caused by HCl supplementation, as indicated by blood and urine acid-base measurements. 4. With the MgO-supplemented diets, values for the faecal and urinary excretion of magnesium were approximately 70 and 10% respectively of Mg intake and were not significantly affected by HCl supplementation. For rumen fluid, the water-soluble Mg concentration as a percentage of the total Mg concentration was similar for each treatment, approximately 90%. For faeces, the corresponding value was also similar for each treatment, approximately 30%. 5. MgO supplementation altered the effect of dietary HCl on faecal calcium excretion and on the balance of Ca, but did not alter its effect on urinary Ca excretion. 6. It is concluded that the beneficial effect of MgO supplementation on the intake of the HCl-treated diet was related more to its influence on dietary pH than on conditions in the rumen or the acid-base balance of the sheep."}
{"id": "PMID:240381", "title": "Cobalt-cytochrome c. II. Magnetic resonance spectra and conformational transitions.", "content": "Between pH approximately 4 and 10 cobaltocytochrome c (Cocyt-c) gives an electron paramagnetic resonance (EPR) spectrum with g parallel = 2.035, g the perpendicular = 2.223, CoA PARALLEL = 61.4 G, CoA the perpendicular = 49.8 G, NA parallel = 15.3 G, and NA THE PERPENDICULAR = 12.5 G. Comparisons with the EPR spectra of deoxycobaltomyoglobin, deoxycobaltohemoglobin, and model compounds and together with other evidence showed cobaltocytochrome c to have Met-80 and His-18 as its axial ligands. The protons of these ligands are seen as resonances shifted by the ring-current field of the porphyrin in the 300-MHZ 1H nuclear magnetic resonance (NMR) spectra of cobalticytochrome c (Cocyt-c+). The methyl and gamma-methylene protons of Met-80 in this molecule occupy positions with respect to heme c which are somewhat different from those in ferrocytochrome c. The 1H NMR spectra also showed that the methyl groups of Leu-32, Ile-75, Thr-63, thioether bridges, and the porphyrin ring in the cobalt protein are in the same state as in native enzyme; the same is also true for Tyr-59, His-26, and His-33 and also possibly Tyr-67, Tyr-74, and Phe-82. Above pH 11, Cocyt-c is converted to a five-coordinated form having g parallel = 2.026, g the perpendicular = 2.325, CoA parallel = 80 G, CoA the perpendicular approximately 10 G, NA parallel = 17.5 G, and NA the perpendicular not resolved. Below pH 1.0 the EPR spectrum of Cocyt-c is also five-coordinated with g parallel = 2.014, g the perpendicular = 2.359, CoA parallel = 93.8 G, and CoA the perpendicular = 38.8 G. The axial ligands in the alkaline and the acidic forms of Cocyt-c are His-18 and Met-80, respectively. New prominent proton resonance peaks are observed in cobalt-cytochrome c which are either absent or weak in native cytochrome c. These are situated at 3.0, 1.7, and 1.44 ppm, attributable, respectively, to the epsilon-CH2, DELTA-CH2 + beta-CH2, and gamma-CH2 of lysyl residues in random-coil-peptides. From the areas of these peaks, it is estimated that one-two lysyl residues in Cocyt-c have been modified; four-five lysyl residues in Cocyt-c+ have been modified. These alterations of surface charged groups are probably responsible for the lowered reactivity of Cocyt-c with cytochrome oxidase and the lack of reactivity of Cocyt-c+ with several cytochrome reductase systems.", "contents": "Cobalt-cytochrome c. II. Magnetic resonance spectra and conformational transitions. Between pH approximately 4 and 10 cobaltocytochrome c (Cocyt-c) gives an electron paramagnetic resonance (EPR) spectrum with g parallel = 2.035, g the perpendicular = 2.223, CoA PARALLEL = 61.4 G, CoA the perpendicular = 49.8 G, NA parallel = 15.3 G, and NA THE PERPENDICULAR = 12.5 G. Comparisons with the EPR spectra of deoxycobaltomyoglobin, deoxycobaltohemoglobin, and model compounds and together with other evidence showed cobaltocytochrome c to have Met-80 and His-18 as its axial ligands. The protons of these ligands are seen as resonances shifted by the ring-current field of the porphyrin in the 300-MHZ 1H nuclear magnetic resonance (NMR) spectra of cobalticytochrome c (Cocyt-c+). The methyl and gamma-methylene protons of Met-80 in this molecule occupy positions with respect to heme c which are somewhat different from those in ferrocytochrome c. The 1H NMR spectra also showed that the methyl groups of Leu-32, Ile-75, Thr-63, thioether bridges, and the porphyrin ring in the cobalt protein are in the same state as in native enzyme; the same is also true for Tyr-59, His-26, and His-33 and also possibly Tyr-67, Tyr-74, and Phe-82. Above pH 11, Cocyt-c is converted to a five-coordinated form having g parallel = 2.026, g the perpendicular = 2.325, CoA parallel = 80 G, CoA the perpendicular approximately 10 G, NA parallel = 17.5 G, and NA the perpendicular not resolved. Below pH 1.0 the EPR spectrum of Cocyt-c is also five-coordinated with g parallel = 2.014, g the perpendicular = 2.359, CoA parallel = 93.8 G, and CoA the perpendicular = 38.8 G. The axial ligands in the alkaline and the acidic forms of Cocyt-c are His-18 and Met-80, respectively. New prominent proton resonance peaks are observed in cobalt-cytochrome c which are either absent or weak in native cytochrome c. These are situated at 3.0, 1.7, and 1.44 ppm, attributable, respectively, to the epsilon-CH2, DELTA-CH2 + beta-CH2, and gamma-CH2 of lysyl residues in random-coil-peptides. From the areas of these peaks, it is estimated that one-two lysyl residues in Cocyt-c have been modified; four-five lysyl residues in Cocyt-c+ have been modified. These alterations of surface charged groups are probably responsible for the lowered reactivity of Cocyt-c with cytochrome oxidase and the lack of reactivity of Cocyt-c+ with several cytochrome reductase systems."}
{"id": "PMID:240382", "title": "Correlation proton magnetic resonance studies at 250 MHz of bovine pancreatic ribonuclease. I. Reinvestigation of the histidine peak assignments.", "content": "The deuterium exchange kinetics of the C(2) protons of the four histidine residues of native bovine pancreatic ribonuclease A have been followed at pH 6.5 and 8.0 by proton magnetic resonance spectroscopy (1H NMR). Comparison of the order of exchange of the histidine peaks with tritium exchange rates into individual histidine residues [Ohe, M., Matsuo, H., Sakiyama, F., and Narita, K. (1974), J. Biochem. (Tokyo) 75, 1197] supports the previous assignment of histidine NMR peaks H(1) and H(4) to histidine-105 and histidine-48 but requires reassignment of peaks H(2) and H(3) to histidine-119 and histidine-12, respectively. Ribonuclease A samples having differentially deuterated histidines have been used to verify the existence of crossover points in the histidine proton magnetic resonance titration curves and to observe the discontinuous titration curve of histidine-48. Proton magnetic resonance peaks have been assigned to the C(4) protons of the four histidine residues of ribonuclease A on the basis of their unit proton areas and by matching their titration shifts with the more readily visible C(2)-H peaks of the histidines. The pK' values derived from the C(4)-H data agree, within experimental limits, with those derived from C(2)-H data. The C(4)-H peaks were assigned to histidine-12, -48, -105, and -119 of ribonuclease A on the basis of their pH dependence, pK' values, shifts of their pK' values in the presence of inhibitor cytidine 3'-phosphate, and by comparison with the assignments of the histidine C(2)-H peaks above.", "contents": "Correlation proton magnetic resonance studies at 250 MHz of bovine pancreatic ribonuclease. I. Reinvestigation of the histidine peak assignments. The deuterium exchange kinetics of the C(2) protons of the four histidine residues of native bovine pancreatic ribonuclease A have been followed at pH 6.5 and 8.0 by proton magnetic resonance spectroscopy (1H NMR). Comparison of the order of exchange of the histidine peaks with tritium exchange rates into individual histidine residues [Ohe, M., Matsuo, H., Sakiyama, F., and Narita, K. (1974), J. Biochem. (Tokyo) 75, 1197] supports the previous assignment of histidine NMR peaks H(1) and H(4) to histidine-105 and histidine-48 but requires reassignment of peaks H(2) and H(3) to histidine-119 and histidine-12, respectively. Ribonuclease A samples having differentially deuterated histidines have been used to verify the existence of crossover points in the histidine proton magnetic resonance titration curves and to observe the discontinuous titration curve of histidine-48. Proton magnetic resonance peaks have been assigned to the C(4) protons of the four histidine residues of ribonuclease A on the basis of their unit proton areas and by matching their titration shifts with the more readily visible C(2)-H peaks of the histidines. The pK' values derived from the C(4)-H data agree, within experimental limits, with those derived from C(2)-H data. The C(4)-H peaks were assigned to histidine-12, -48, -105, and -119 of ribonuclease A on the basis of their pH dependence, pK' values, shifts of their pK' values in the presence of inhibitor cytidine 3'-phosphate, and by comparison with the assignments of the histidine C(2)-H peaks above."}
{"id": "PMID:240383", "title": "Correlation proton magnetic resonance studies at 250 MHz of bovine pancreatic ribonuclease. III. Mutual electrostatic interaction between histidine residues 12 and 119.", "content": "The two adjacent active site histidine residues of bovine pancreatic ribonuclease A (histidine-12 and -119) yield proton magnetic resonance titration curves having Hill coefficients significantly less than unity (0.7 and 0.8, respectively). Three models postulating interactions with other titrating groups in the molecule have been used to approximate these anomalous experimental titration curves. Very good agreement with the data was obtained with models postulating mutual electrostatic interaction between histidine-12 and -119. The additional low pH perturbation of the chemical shift of the C(2)-H peak (but not the C(4)-H peak) of histidine-12 is attributed to a local conformational change with a pHmid of about 3.5.", "contents": "Correlation proton magnetic resonance studies at 250 MHz of bovine pancreatic ribonuclease. III. Mutual electrostatic interaction between histidine residues 12 and 119. The two adjacent active site histidine residues of bovine pancreatic ribonuclease A (histidine-12 and -119) yield proton magnetic resonance titration curves having Hill coefficients significantly less than unity (0.7 and 0.8, respectively). Three models postulating interactions with other titrating groups in the molecule have been used to approximate these anomalous experimental titration curves. Very good agreement with the data was obtained with models postulating mutual electrostatic interaction between histidine-12 and -119. The additional low pH perturbation of the chemical shift of the C(2)-H peak (but not the C(4)-H peak) of histidine-12 is attributed to a local conformational change with a pHmid of about 3.5."}
{"id": "PMID:240384", "title": "Limited hydrolysis of bovine plasma albumin at neutral and alkaline pH catalyzed by associated proteinases.", "content": "Proteinase contaminants in some plasma albumin samples have previously been shown to produce cleavage of the albumin molecule at acid pH. The F conformer, existing at pH 3.8, is cleaved near erisidue number 400 to yield a large N-terminal fragment of approximately 46,000 daltons. No cleavage was found at pH above approximately 4.4. It is shown in this paper that the proteinase contaminants are active over a broad pH range from 2.5 to 11.4 provided conditions are such as to induce some breakdown of the native conformation of the albumin molecule. Addition of Tris-borate buffer (0.1 M) at pH 7.5-9 is sufficient to permit cleavage. At pH near 9 this occurs predominantly 42,000 and 27,000 daltons. Near neutral pH substantial cleavage occurs in 4-8 M urea solution or in the presence of sodium dodecyl sulfate (AD110 complex). Under these conditions there are two large fragments (42,000 and 47,000 daltons) and essentially two small ones (20,000-27,000 daltons). Under conditions where there is no cleavage at 38-40 degrees, substantial cleavage results at 50-65 degrees but enzyme inactivation also occurs toward the top of this range. The alkaline activity is inhibited by soybean trypsin inhibitor but not by pepstatin; the reverse is true of the low pH activity. Cleavage at neutral or alkaline pH under the various conditions occurs primarily at X-Leu bonds while the low pH activity was already shown to occur at X-Phe. These facts suggest the presence of at least two enzymes. There is surprisingly little pH dependence over the range 7.5-9 in any of the media examined, even though albumin is known to undergo a significant conformational change in this range, the N leads to B transition. This transition is thought to be essentially a tertiary change with little loss of helix content. It is suggested that loss of native secondary structure, especially uncoiling of helical regions, is crucial to permit attack by these enzymes.", "contents": "Limited hydrolysis of bovine plasma albumin at neutral and alkaline pH catalyzed by associated proteinases. Proteinase contaminants in some plasma albumin samples have previously been shown to produce cleavage of the albumin molecule at acid pH. The F conformer, existing at pH 3.8, is cleaved near erisidue number 400 to yield a large N-terminal fragment of approximately 46,000 daltons. No cleavage was found at pH above approximately 4.4. It is shown in this paper that the proteinase contaminants are active over a broad pH range from 2.5 to 11.4 provided conditions are such as to induce some breakdown of the native conformation of the albumin molecule. Addition of Tris-borate buffer (0.1 M) at pH 7.5-9 is sufficient to permit cleavage. At pH near 9 this occurs predominantly 42,000 and 27,000 daltons. Near neutral pH substantial cleavage occurs in 4-8 M urea solution or in the presence of sodium dodecyl sulfate (AD110 complex). Under these conditions there are two large fragments (42,000 and 47,000 daltons) and essentially two small ones (20,000-27,000 daltons). Under conditions where there is no cleavage at 38-40 degrees, substantial cleavage results at 50-65 degrees but enzyme inactivation also occurs toward the top of this range. The alkaline activity is inhibited by soybean trypsin inhibitor but not by pepstatin; the reverse is true of the low pH activity. Cleavage at neutral or alkaline pH under the various conditions occurs primarily at X-Leu bonds while the low pH activity was already shown to occur at X-Phe. These facts suggest the presence of at least two enzymes. There is surprisingly little pH dependence over the range 7.5-9 in any of the media examined, even though albumin is known to undergo a significant conformational change in this range, the N leads to B transition. This transition is thought to be essentially a tertiary change with little loss of helix content. It is suggested that loss of native secondary structure, especially uncoiling of helical regions, is crucial to permit attack by these enzymes."}
{"id": "PMID:240385", "title": "Kinetic investigation of unfolding and partial refolding of a crab satellite (dA-dT)n.", "content": "Crab (dA-dT)n was isolated from the testes of Cancer borealis by a procedure involving separation of DNA and segregation of the satellite fraction by Hg2+ binding/Cs2SO4 density gradient ultracentrifugation. The titration of crab (dA-dT)n samples at 10 degrees indicated a sharp absorbance change at pH 11.98 in agreement with the pHm value observed for synthetic poly(dA-dT) under identical conditions. The reversal of the titration, however, resulted only in about 50% recovery of the original absorbance (at 260 nm) in marked contrast to the complete reversibility of the synthetic material. pH-jump experiments were carried out for the purpose of characterizing the rates and mechanisms of conformational transitions brought about by changes in the solution environment. It was found that the disintegration of the putative native structure of crab (dA-dT)n starts with a very fast reaction (occurring within the 6-msec deadtime of the instrument and comprising 65% of the total absorbance change) and it is completed via a slower first-order reaction (k = 66 sec minus 1). It is postulated that the first process is due to the rapid untwisting of end regions and, perhaps, some short hairpin-like helical branches present on the macromolecules. The second reaction is believed to be the end-to-end type unwinding of the double-helical backbone of crab (dA-dT)n. In the presence of low concentration (3 mug/ml) of Hg2+ ions the overall rate of disintegration process decreased drastically. pH jumps from pH values above pHm to values below were used to study the rates of absorbance changes corresponding to the refolding of the strands of denatured crab (DA-dT)n. A concentration independent process consisting of two phases was observed. The first phase was a gradual nonexponential process spanning the first second of the reaction, and the other, a very slow first-order process characterized by the rate constant value of 0.053 sec minus 1. It is proposed that the first part of the process (involving about 24% of nucleotide residues) is an intramolecular formation of helical hairpins (frequently interrupted by mismatching bases) and the second part is a manifestation of some association of the extant unpaired bases during the folding of the branched structure. Refolded crab (dA-dT)n samples when subjected again to pH greater than pHm in the stopped-flow apparatus displayed not the disintegration pattern of the native crab (dA-dT)n but rather that of synthetic poly(dA-dT. The marked facility of crab (dA-dT)n macromolecules for rapid conformational transitions induced by slight changes in the solution environment might be relevant to the biological function of this DNA.", "contents": "Kinetic investigation of unfolding and partial refolding of a crab satellite (dA-dT)n. Crab (dA-dT)n was isolated from the testes of Cancer borealis by a procedure involving separation of DNA and segregation of the satellite fraction by Hg2+ binding/Cs2SO4 density gradient ultracentrifugation. The titration of crab (dA-dT)n samples at 10 degrees indicated a sharp absorbance change at pH 11.98 in agreement with the pHm value observed for synthetic poly(dA-dT) under identical conditions. The reversal of the titration, however, resulted only in about 50% recovery of the original absorbance (at 260 nm) in marked contrast to the complete reversibility of the synthetic material. pH-jump experiments were carried out for the purpose of characterizing the rates and mechanisms of conformational transitions brought about by changes in the solution environment. It was found that the disintegration of the putative native structure of crab (dA-dT)n starts with a very fast reaction (occurring within the 6-msec deadtime of the instrument and comprising 65% of the total absorbance change) and it is completed via a slower first-order reaction (k = 66 sec minus 1). It is postulated that the first process is due to the rapid untwisting of end regions and, perhaps, some short hairpin-like helical branches present on the macromolecules. The second reaction is believed to be the end-to-end type unwinding of the double-helical backbone of crab (dA-dT)n. In the presence of low concentration (3 mug/ml) of Hg2+ ions the overall rate of disintegration process decreased drastically. pH jumps from pH values above pHm to values below were used to study the rates of absorbance changes corresponding to the refolding of the strands of denatured crab (DA-dT)n. A concentration independent process consisting of two phases was observed. The first phase was a gradual nonexponential process spanning the first second of the reaction, and the other, a very slow first-order process characterized by the rate constant value of 0.053 sec minus 1. It is proposed that the first part of the process (involving about 24% of nucleotide residues) is an intramolecular formation of helical hairpins (frequently interrupted by mismatching bases) and the second part is a manifestation of some association of the extant unpaired bases during the folding of the branched structure. Refolded crab (dA-dT)n samples when subjected again to pH greater than pHm in the stopped-flow apparatus displayed not the disintegration pattern of the native crab (dA-dT)n but rather that of synthetic poly(dA-dT. The marked facility of crab (dA-dT)n macromolecules for rapid conformational transitions induced by slight changes in the solution environment might be relevant to the biological function of this DNA."}
{"id": "PMID:240386", "title": "Model studies for molybdenum enzymes. The reduction of cytochrome c by molybdenum(V)-cysteine complexes.", "content": "The reduction of ferricytochrome c by two molybdenum(V)-cysteine complexes has been investigated as a model for electron transfer in the molybdenum enzymes sulfite oxidase and nitrate reductase. The reduction by the dioxo-bridged Mo(V)-cysteine complex, di-mu-oxo-bis-[oxo(L-cysteinato)molybdate(V)] (I), is relatively slow and its rate is first order in cyt cIII and zero order in I (k = (1.09 +/- 0.10) times 10(-3) sec minus 1, pH 7.5, 20 degrees). The reduction by the monoxo-bridged complex, mu-oxo-bis[oxodihydroxo(L-cysteinato)molybdate(V)] (II), is extremely rapid and its rate is first order in both reactants (k = (2.6 +/- 0.7) times 10(7) M minus 1 sec minus 1, pH 7.0, 25 degrees). Above pH 7.5, the reduction by II follows biphasic kinetics due to the fast reduction of a low pH form of cyt cIII and a slower reduction of a high pH form (at pH 10.0, 25 degrees, k = 2.9 times 10(6) M minus 1 sec minus 1 for the low pH form and k = 7.2 times 10(4) M minus 1 sec minus 1 for the high pH form). Reaction mechanisms for reductions by both I and II are proposed and the biological implications of the results, both for sulfite oxidase and mechanisms of electron transfer to cytochrome c, are discussed.", "contents": "Model studies for molybdenum enzymes. The reduction of cytochrome c by molybdenum(V)-cysteine complexes. The reduction of ferricytochrome c by two molybdenum(V)-cysteine complexes has been investigated as a model for electron transfer in the molybdenum enzymes sulfite oxidase and nitrate reductase. The reduction by the dioxo-bridged Mo(V)-cysteine complex, di-mu-oxo-bis-[oxo(L-cysteinato)molybdate(V)] (I), is relatively slow and its rate is first order in cyt cIII and zero order in I (k = (1.09 +/- 0.10) times 10(-3) sec minus 1, pH 7.5, 20 degrees). The reduction by the monoxo-bridged complex, mu-oxo-bis[oxodihydroxo(L-cysteinato)molybdate(V)] (II), is extremely rapid and its rate is first order in both reactants (k = (2.6 +/- 0.7) times 10(7) M minus 1 sec minus 1, pH 7.0, 25 degrees). Above pH 7.5, the reduction by II follows biphasic kinetics due to the fast reduction of a low pH form of cyt cIII and a slower reduction of a high pH form (at pH 10.0, 25 degrees, k = 2.9 times 10(6) M minus 1 sec minus 1 for the low pH form and k = 7.2 times 10(4) M minus 1 sec minus 1 for the high pH form). Reaction mechanisms for reductions by both I and II are proposed and the biological implications of the results, both for sulfite oxidase and mechanisms of electron transfer to cytochrome c, are discussed."}
{"id": "PMID:240387", "title": "Effects of pH and thiols on the kinetics of yeast glyoxalase I. An evaluation of the random pathway mechanism.", "content": "The disproportionation of alpha-ketoaldehydes, catalyzed by yeast glyoxalase I, has been reported to involve a random pathway mechanism where one branch utilizes the hemimercaptal of glutathione and the alpha-ketoaldehyde in a one-substrate pathway, and the other branch utilizes first glutathione and then the alpha-ketoaldehyde in an ordered two-substrate pathway. The relative importance of the two pathways has been evaluated at 5 degrees in the pH range 3-7, using methylglyoxal and phenylglyoxal as representative aliphatic and aromatic alpha-ketoaldehydes, by comparing initial rates of hemimercaptal formation in the absence of enzyme with initial rates of product formation in the presence of high enzyme concentrations. If the enzyme is not added last, the initial rates of product formation are the same as the initial rates of adduct formation even under conditions where it could be shown that dehydration of the hydrated alpha-ketoaldehyde is not entirely rate determining. If the enzyme is added after hemimercaptal formation, there is a \"burst\" of product formation equivalent to the amount of hemimercaptal, followed by a slower reaction, consistent with the one-substrate pathway. Additional support for this pathway was obtained from a study of the effects of added thiol reagents on the \"burst\" kinetics. The broad specificity of yeast glyoxalase I for both aliphatic and aromatic alpha-ketoaldehydes, reflected in Vmax values which are insensitive to the nature of the alpha-ketoaldehyde drops abruptly if the side chain of the alpha-ketoaldehyde is sterically crowded. The hemimercaptal of tert-butylglyoxal has a Vmax 300-fold smaller than Vmax for methylglyoxal; 2,4,6-trimethylphenylglyoxal is essentially inactive as a substrate even though the closely related compound 2,4-dimethylphenylglyoxal is a normal substrate. Analysis of the Vmax and Km (or Ki) values of these alpha-ketoaldehydes suggests that sterically crowded side chains affect both enzyme-substrate formation and the catalytic reaction.", "contents": "Effects of pH and thiols on the kinetics of yeast glyoxalase I. An evaluation of the random pathway mechanism. The disproportionation of alpha-ketoaldehydes, catalyzed by yeast glyoxalase I, has been reported to involve a random pathway mechanism where one branch utilizes the hemimercaptal of glutathione and the alpha-ketoaldehyde in a one-substrate pathway, and the other branch utilizes first glutathione and then the alpha-ketoaldehyde in an ordered two-substrate pathway. The relative importance of the two pathways has been evaluated at 5 degrees in the pH range 3-7, using methylglyoxal and phenylglyoxal as representative aliphatic and aromatic alpha-ketoaldehydes, by comparing initial rates of hemimercaptal formation in the absence of enzyme with initial rates of product formation in the presence of high enzyme concentrations. If the enzyme is not added last, the initial rates of product formation are the same as the initial rates of adduct formation even under conditions where it could be shown that dehydration of the hydrated alpha-ketoaldehyde is not entirely rate determining. If the enzyme is added after hemimercaptal formation, there is a \"burst\" of product formation equivalent to the amount of hemimercaptal, followed by a slower reaction, consistent with the one-substrate pathway. Additional support for this pathway was obtained from a study of the effects of added thiol reagents on the \"burst\" kinetics. The broad specificity of yeast glyoxalase I for both aliphatic and aromatic alpha-ketoaldehydes, reflected in Vmax values which are insensitive to the nature of the alpha-ketoaldehyde drops abruptly if the side chain of the alpha-ketoaldehyde is sterically crowded. The hemimercaptal of tert-butylglyoxal has a Vmax 300-fold smaller than Vmax for methylglyoxal; 2,4,6-trimethylphenylglyoxal is essentially inactive as a substrate even though the closely related compound 2,4-dimethylphenylglyoxal is a normal substrate. Analysis of the Vmax and Km (or Ki) values of these alpha-ketoaldehydes suggests that sterically crowded side chains affect both enzyme-substrate formation and the catalytic reaction."}
{"id": "PMID:240388", "title": "Biodegradative ornithine decarboxylase of Escherichia coli. Purification, properties, and pyridoxal 5'-phosphate binding site.", "content": "The biodegradative ornithine decarboxylase of Escherichia coli has been purified to apparent homogeneity. At its pH optimum (pH 7.0), the enzyme exists as a dimer of 160,000 molecular weight. Aggregation of the dimer was promoted by lower pH values. The enzyme requires pyridoxal 5'-phosphate for activity. The coenzyme appears to be bound in Schiff base linkage as suggested by spectral studies and inhibition by NaBH4. The following sequence was determined for the coenzyme binding site: Val-His-(epsilon-Pxy)Lys-Gln-Gln-Ala-Gly-Gln. The properties of this enzyme are compared with the other biodegradative amino acid decarboxylases that have been isolated from E. coli.", "contents": "Biodegradative ornithine decarboxylase of Escherichia coli. Purification, properties, and pyridoxal 5'-phosphate binding site. The biodegradative ornithine decarboxylase of Escherichia coli has been purified to apparent homogeneity. At its pH optimum (pH 7.0), the enzyme exists as a dimer of 160,000 molecular weight. Aggregation of the dimer was promoted by lower pH values. The enzyme requires pyridoxal 5'-phosphate for activity. The coenzyme appears to be bound in Schiff base linkage as suggested by spectral studies and inhibition by NaBH4. The following sequence was determined for the coenzyme binding site: Val-His-(epsilon-Pxy)Lys-Gln-Gln-Ala-Gly-Gln. The properties of this enzyme are compared with the other biodegradative amino acid decarboxylases that have been isolated from E. coli."}
{"id": "PMID:240389", "title": "Reversible reaction of cyanate with a reactive sulfhydryl group at the glutamine binding site of carbamyl phosphate synthetase.", "content": "Carbamyl phosphate synthetase from Escherichia coli reacts stoichiometrically (one to one) with [14C]cyanate to give a 14C-labeled complex which can be isolated by gel filtration. The formation of the complex is prevented if L-glutamine is present or if the enzyme is first reacted with 2-amino-4-oxo-5-chloropentanoic acid, a chloro ketone analog of glutamine which has been shown to react with a specific SH group in the glutamine binding site. The rate of complex formation is increased by ADP and decreased by ATP and HCO3-. The isolated complex is inactive with respect to glutamine-dependent synthetase activity. However, the reaction of cyanate with the enzyme is reversible. The rate of dissociation of the isolated complex is not affected by pH (over the pH range 6-10), is greatly increased by ATP and HCO3-, and is decreased by ADP. The allosteric effectors ornithine and UMP have no effect on either the rate of formation or the rate of dissociation of the complex; however, the apparent affinity of the enzyme for ATP is decreased by UMP and increased by ornithine. The site of reaction of cyanate with carbamyl phosphate synthetase, which is composed of a light and a heavy subunit, is with an SH group in the light subunit to give an S-carbamylcysteine residue. The binding of L-[14C]glutamine to the enzyme and the inhibition of glutamine-dependent synthetase activity by the chloroketone analog are both prevented by the presence of cyanate. The reaction with cyanate is considered to be with the same essential SH group which is located in the glutamine binding site and is alkylated by 2-amino-4-oxo-5-chloropentanoic acid. The bicarbonate-dependent effects of ATP suggest that formation of the activated carbon dioxide intermediate is accompanied by changes in the heavy subunit which functionally alter the properties of the glutamine binding site on the light subunit. The allosteric effects of ornithine and UMP are probably not related to this intersubunit interaction.", "contents": "Reversible reaction of cyanate with a reactive sulfhydryl group at the glutamine binding site of carbamyl phosphate synthetase. Carbamyl phosphate synthetase from Escherichia coli reacts stoichiometrically (one to one) with [14C]cyanate to give a 14C-labeled complex which can be isolated by gel filtration. The formation of the complex is prevented if L-glutamine is present or if the enzyme is first reacted with 2-amino-4-oxo-5-chloropentanoic acid, a chloro ketone analog of glutamine which has been shown to react with a specific SH group in the glutamine binding site. The rate of complex formation is increased by ADP and decreased by ATP and HCO3-. The isolated complex is inactive with respect to glutamine-dependent synthetase activity. However, the reaction of cyanate with the enzyme is reversible. The rate of dissociation of the isolated complex is not affected by pH (over the pH range 6-10), is greatly increased by ATP and HCO3-, and is decreased by ADP. The allosteric effectors ornithine and UMP have no effect on either the rate of formation or the rate of dissociation of the complex; however, the apparent affinity of the enzyme for ATP is decreased by UMP and increased by ornithine. The site of reaction of cyanate with carbamyl phosphate synthetase, which is composed of a light and a heavy subunit, is with an SH group in the light subunit to give an S-carbamylcysteine residue. The binding of L-[14C]glutamine to the enzyme and the inhibition of glutamine-dependent synthetase activity by the chloroketone analog are both prevented by the presence of cyanate. The reaction with cyanate is considered to be with the same essential SH group which is located in the glutamine binding site and is alkylated by 2-amino-4-oxo-5-chloropentanoic acid. The bicarbonate-dependent effects of ATP suggest that formation of the activated carbon dioxide intermediate is accompanied by changes in the heavy subunit which functionally alter the properties of the glutamine binding site on the light subunit. The allosteric effects of ornithine and UMP are probably not related to this intersubunit interaction."}
{"id": "PMID:240390", "title": "Isolation and characterization of papaya peptidase A from commercial chymopapain.", "content": "Chromatography on a column of SP-Sephadex shows that commercial chymopapain contains three components with proteolytic activity. Each behaves as a single protein upon rechromatography and electrophoresis on polyacrylamide gels. The major component, which represents 31% of the activity applied to the column and is the most basic protein, was identified as papaya peptidase A. This enzyme has no methionine and isoleucine on its N-terminus. Its molecular weight is about 24,000 as determined by sodium dodecyl sulfate polyacrylamide electrophoresis and sedimentation equilibrium centrifugation. Its fluorescence emission as a function of pH resembles that for unactivated papain. Reduction is required for full activity, and in general it is less active than papain against substrates such as casein, N-benzoyl-L-arginine ethyl ester, N-tosyl-L-arginine methyl ester, N-benzoyl-L-arginineamide, and N-benzoyl-DL-arginine p-nitroanilide. Of the other components isolated from crude chymopapain, the more acidic enzyme contains 20% of the activity applied to the column, has a molecular weight of about 25,000, and N-terminal residues of tyrosine and glutamic acid. The other enzyme represents 26% of the initial activity, has a molecular weight of about 28,000 and tyrosine on its N-terminus. Both proteins have a single residue of methionine per molecule. The more acidic component resembles chymopapain A, and the other enzyme is similar to chymopapain B.", "contents": "Isolation and characterization of papaya peptidase A from commercial chymopapain. Chromatography on a column of SP-Sephadex shows that commercial chymopapain contains three components with proteolytic activity. Each behaves as a single protein upon rechromatography and electrophoresis on polyacrylamide gels. The major component, which represents 31% of the activity applied to the column and is the most basic protein, was identified as papaya peptidase A. This enzyme has no methionine and isoleucine on its N-terminus. Its molecular weight is about 24,000 as determined by sodium dodecyl sulfate polyacrylamide electrophoresis and sedimentation equilibrium centrifugation. Its fluorescence emission as a function of pH resembles that for unactivated papain. Reduction is required for full activity, and in general it is less active than papain against substrates such as casein, N-benzoyl-L-arginine ethyl ester, N-tosyl-L-arginine methyl ester, N-benzoyl-L-arginineamide, and N-benzoyl-DL-arginine p-nitroanilide. Of the other components isolated from crude chymopapain, the more acidic enzyme contains 20% of the activity applied to the column, has a molecular weight of about 25,000, and N-terminal residues of tyrosine and glutamic acid. The other enzyme represents 26% of the initial activity, has a molecular weight of about 28,000 and tyrosine on its N-terminus. Both proteins have a single residue of methionine per molecule. The more acidic component resembles chymopapain A, and the other enzyme is similar to chymopapain B."}
{"id": "PMID:240391", "title": "Correlation proton magnetic resonance studies at 250 MHz of bovine pancreatic ribonuclease. II. pH and inhibitor-induced conformational transitions affecting histidine-48 and one tyrosine residue of ribonuclease A.", "content": "The microenvironment of histidine-48 of bovine pancreatic ribonuclease A was investigated by proton magnetic resonance spectroscopy (1H NMR) using partially deuterated enzyme in which resolution of the C(2)-H resonance of histidine-48 was simplified. The NMR titration curves at 100 and 250 MHz of histidine-48 of ribonuclease A are discontinuous both for the enzyme alone in 0.3 M chloride and for its complex with cytidine 3'-phosphate. This suggests that titration of histidine-48 occurs only as the result of a slow conformational transition. The sum of the peaks corresponding to histidine-48 in the acid-stable and base-stable forms of the enzyme is less than one proton in the transition region, which indicates that there exists at least one intermediate conformational form of the enzyme. The transition from the acid-stable form to an intermediate form has a pHmid of 5.6, and the transition from an intermediate form to the base-stable form has a pHmid of 6.9. In ribonuclease S and in ribonuclease A in the presence of 0.3 M acetate, the titration curve of histidine-48 is continuous, and the area of the peak is uniform throughout the titration. Proton NMR difference spectra at 100 and 250 MHz reveal a pH-induced conformational change with a pHmid of 5.7 that affects the chemical shift of a single tyrosine residue. This conformational transition is absent in ribonuclease S and is altered in ribonuclease A by the presence of either acetate or cytidine 3'-monophosphate. It is postulated that the same conformational transition is responsible for both the tyrosine perturbation and the disappearance of the histidine-48 peak observed in the acid-stable form of the enzyme. It is proposed that the perturbed tyrosine is tyrosine-25. The transition with pHmid 5.6 is attributed to dissociation of aspartic acid-14, and the transition with pHmid 6.9 is assigned to dissociation of histidine-48. A peak in the aromatic region that moves upfield on addition of the competitive inhibitor cytidine 3'-monophosphate is assigned to a tyrosine, and evidence is presented that this tyrosine is tyrosine-25. Inhibitor binding appears to induce a conformational change in the histidine-48/tyrosine-25 region which is remote from the active site.", "contents": "Correlation proton magnetic resonance studies at 250 MHz of bovine pancreatic ribonuclease. II. pH and inhibitor-induced conformational transitions affecting histidine-48 and one tyrosine residue of ribonuclease A. The microenvironment of histidine-48 of bovine pancreatic ribonuclease A was investigated by proton magnetic resonance spectroscopy (1H NMR) using partially deuterated enzyme in which resolution of the C(2)-H resonance of histidine-48 was simplified. The NMR titration curves at 100 and 250 MHz of histidine-48 of ribonuclease A are discontinuous both for the enzyme alone in 0.3 M chloride and for its complex with cytidine 3'-phosphate. This suggests that titration of histidine-48 occurs only as the result of a slow conformational transition. The sum of the peaks corresponding to histidine-48 in the acid-stable and base-stable forms of the enzyme is less than one proton in the transition region, which indicates that there exists at least one intermediate conformational form of the enzyme. The transition from the acid-stable form to an intermediate form has a pHmid of 5.6, and the transition from an intermediate form to the base-stable form has a pHmid of 6.9. In ribonuclease S and in ribonuclease A in the presence of 0.3 M acetate, the titration curve of histidine-48 is continuous, and the area of the peak is uniform throughout the titration. Proton NMR difference spectra at 100 and 250 MHz reveal a pH-induced conformational change with a pHmid of 5.7 that affects the chemical shift of a single tyrosine residue. This conformational transition is absent in ribonuclease S and is altered in ribonuclease A by the presence of either acetate or cytidine 3'-monophosphate. It is postulated that the same conformational transition is responsible for both the tyrosine perturbation and the disappearance of the histidine-48 peak observed in the acid-stable form of the enzyme. It is proposed that the perturbed tyrosine is tyrosine-25. The transition with pHmid 5.6 is attributed to dissociation of aspartic acid-14, and the transition with pHmid 6.9 is assigned to dissociation of histidine-48. A peak in the aromatic region that moves upfield on addition of the competitive inhibitor cytidine 3'-monophosphate is assigned to a tyrosine, and evidence is presented that this tyrosine is tyrosine-25. Inhibitor binding appears to induce a conformational change in the histidine-48/tyrosine-25 region which is remote from the active site."}
{"id": "PMID:240392", "title": "The self-association of the reduced ApoA-II apoprotein from the human high density lipoprotein complex.", "content": "The molecular properties of the single linear chain form of human apoA-II, i.e., Cm apoA-II, have been evaluated by circular dichroism, polarization of fluorescence, difference absorption, and sedimentation equilibrium. The self-association of Cm apoA-II to a dimer resembles closely that of apoA-II though the free energy change is somewhat smaller. The dimerization of Cm apoA-II is accompanied by major changes in secondary and tertiary structure. The apoA-II molecule, therefore, represents a molecular association where the intramolecular structure is strongly dependent on the quaternary structure.", "contents": "The self-association of the reduced ApoA-II apoprotein from the human high density lipoprotein complex. The molecular properties of the single linear chain form of human apoA-II, i.e., Cm apoA-II, have been evaluated by circular dichroism, polarization of fluorescence, difference absorption, and sedimentation equilibrium. The self-association of Cm apoA-II to a dimer resembles closely that of apoA-II though the free energy change is somewhat smaller. The dimerization of Cm apoA-II is accompanied by major changes in secondary and tertiary structure. The apoA-II molecule, therefore, represents a molecular association where the intramolecular structure is strongly dependent on the quaternary structure."}
{"id": "PMID:240393", "title": "Relation between redox potentials and rate constants in reactions coupled with the system oxygen-superoxide.", "content": "Univalent oxidation-reduction reactions coupled with the oxygen-superoxide system were investigated in the reactions shown in eq 3 and 8, where Q and Q.- stand for p-benzoquinone and p-benzosemiquinone, respectively. From kinetic experiments the following rate constants were obtained at pH 7.0:k3 = 4.5 x 10(4) M-1 sec-1 and k8 = 3 x 10(-2) M-1 sec-1. With known values of k-3 and k-8, and of E0' for the systems Q-Q.- (0.10 V) and Cyt c3+ - Cyt c2+ (0.255 V), the calculated values of E0(O2-O2.-) were found to lie in the range between -0.27 and -0.33 V.", "contents": "Relation between redox potentials and rate constants in reactions coupled with the system oxygen-superoxide. Univalent oxidation-reduction reactions coupled with the oxygen-superoxide system were investigated in the reactions shown in eq 3 and 8, where Q and Q.- stand for p-benzoquinone and p-benzosemiquinone, respectively. From kinetic experiments the following rate constants were obtained at pH 7.0:k3 = 4.5 x 10(4) M-1 sec-1 and k8 = 3 x 10(-2) M-1 sec-1. With known values of k-3 and k-8, and of E0' for the systems Q-Q.- (0.10 V) and Cyt c3+ - Cyt c2+ (0.255 V), the calculated values of E0(O2-O2.-) were found to lie in the range between -0.27 and -0.33 V."}
{"id": "PMID:240394", "title": "Complete tyrosine assignments in the high field 1H nuclear magnetic resonance spectrum of the bovine pancreatic trypsin inhibitor.", "content": "The low-field portions of the 250-MHz 1H nuclear magnetic resonance (NMR) specra of native and chemically modified bovine basic pancreatic trypsin inhibitor (BPTI) have been studied as a function of pH over the range pH 5-13. Resonances associated with the 16 protons of the aromatic rings of the four BPTI tyrosines have been located and assigned to specific tyrosyl residues. Titrations of pH yielded pK's for tyrosines-10, -21, -23, and -35 of 10.4, 11.0, 11.7, and 11.1, respectively. The resonances associated with the nitrotyrosine-10 protons of mononitrated BPTI and the nitrotyrosine-10 and -21 protons of dinitrated BPTI have been similarly located, assigned and titrated yielding pK's for nitrotyrosine-10 and -21 of 6.6 and 6.4, respectively. The high-field NMR spectrum indicates that the aromatic ring of tyrosine-35 rotates less than 160 times per second at 25 degrees for pH's in the range 5-9.", "contents": "Complete tyrosine assignments in the high field 1H nuclear magnetic resonance spectrum of the bovine pancreatic trypsin inhibitor. The low-field portions of the 250-MHz 1H nuclear magnetic resonance (NMR) specra of native and chemically modified bovine basic pancreatic trypsin inhibitor (BPTI) have been studied as a function of pH over the range pH 5-13. Resonances associated with the 16 protons of the aromatic rings of the four BPTI tyrosines have been located and assigned to specific tyrosyl residues. Titrations of pH yielded pK's for tyrosines-10, -21, -23, and -35 of 10.4, 11.0, 11.7, and 11.1, respectively. The resonances associated with the nitrotyrosine-10 protons of mononitrated BPTI and the nitrotyrosine-10 and -21 protons of dinitrated BPTI have been similarly located, assigned and titrated yielding pK's for nitrotyrosine-10 and -21 of 6.6 and 6.4, respectively. The high-field NMR spectrum indicates that the aromatic ring of tyrosine-35 rotates less than 160 times per second at 25 degrees for pH's in the range 5-9."}
{"id": "PMID:240395", "title": "Competitive inhibitors of renin. Inhibitors effective at physiological pH.", "content": "Previously we reported the development of competitive inhibitors of renin effective at pH 5.5 (Poulsen, K., Burton, J., and Haber, E. (1973), Biochemistry 12, 3877). At physiologic pH (7.5), the inhibitory constants (Ki) increased and solubility decreased to the point that inhibition could not be demonstrated with these peptides. Modification of the octapeptide sequence, His-Pro-Phe-His-Leu-Leu-Val-Tyr, either by addition of serinol to the carboxyl terminus or by replacement of valine-7 with an isosteric threonyl residue failed to yield peptides active at pH 7.5. Attachment of polyproline sequences to the amino terminus increased solubility from threefold to tenfold and decreased Ki so that competitive inhibition was demonstrable at physiologic pH. In addition, if leucine-6 was replaced in these peptides with a phenylalanyl or tyrosyl residue, Ki decreased (3-12 muM) to give effective competitive inhibitors at physiologic pH in both buffer and in plasma.", "contents": "Competitive inhibitors of renin. Inhibitors effective at physiological pH. Previously we reported the development of competitive inhibitors of renin effective at pH 5.5 (Poulsen, K., Burton, J., and Haber, E. (1973), Biochemistry 12, 3877). At physiologic pH (7.5), the inhibitory constants (Ki) increased and solubility decreased to the point that inhibition could not be demonstrated with these peptides. Modification of the octapeptide sequence, His-Pro-Phe-His-Leu-Leu-Val-Tyr, either by addition of serinol to the carboxyl terminus or by replacement of valine-7 with an isosteric threonyl residue failed to yield peptides active at pH 7.5. Attachment of polyproline sequences to the amino terminus increased solubility from threefold to tenfold and decreased Ki so that competitive inhibition was demonstrable at physiologic pH. In addition, if leucine-6 was replaced in these peptides with a phenylalanyl or tyrosyl residue, Ki decreased (3-12 muM) to give effective competitive inhibitors at physiologic pH in both buffer and in plasma."}
{"id": "PMID:240396", "title": "Circular dichroism of holo- and apoprotocatechuate 3,4-dioxygenase from Pseudomonas aeruginosa.", "content": "Circular dichroism studies have been carried out on both apo- and holoprotocatechuate 3,4-dioxygenase from Pseudomonas aeruginosa, in the absence and presence of competitive inhibitors, protocatechualdehyde and 4-nitrocatechol. The apo- and holoenzyme showed identical spectra in the ultraviolet region between 200 and 250 nm (peptide back bone region), but the low intensity negative bands at 330 and 480 nm of the holoenzyme were completely absent in the apoenzyme. On the side chain region, the positive ellipticity peaks of the holoenzyme change into a lower intensity and broader band indicating the participation of aromatic amino acid residues in the primary binding of iron ion. Under anaerobic conditions, spectral changes were evident in the side chain region for the binary complexes of both the holo- and the apoenzyme with protocatechuate. The presence of iron in the holoenzyme results in an increase in positive ellipticity between 290 and 320 nm. Either with or without the iron, the enzyme protein binds protocatechuate and has a greater positive circular dichroism increase at 240-260 nm. CD difference spectra indicate that the modes of binding to form the binary complexes of holo- or apoenzyme with either substrates or competitive inhibitors are different. The bound iron ion stimulates binding. Spectral changes of the holoenzyme in the aromatic region were also observed in different pH environments of lower enzymatic activity. It is still not established whether these aromatic residues play an active or passive role in the binding of iron and/or substrates and inhibitors.", "contents": "Circular dichroism of holo- and apoprotocatechuate 3,4-dioxygenase from Pseudomonas aeruginosa. Circular dichroism studies have been carried out on both apo- and holoprotocatechuate 3,4-dioxygenase from Pseudomonas aeruginosa, in the absence and presence of competitive inhibitors, protocatechualdehyde and 4-nitrocatechol. The apo- and holoenzyme showed identical spectra in the ultraviolet region between 200 and 250 nm (peptide back bone region), but the low intensity negative bands at 330 and 480 nm of the holoenzyme were completely absent in the apoenzyme. On the side chain region, the positive ellipticity peaks of the holoenzyme change into a lower intensity and broader band indicating the participation of aromatic amino acid residues in the primary binding of iron ion. Under anaerobic conditions, spectral changes were evident in the side chain region for the binary complexes of both the holo- and the apoenzyme with protocatechuate. The presence of iron in the holoenzyme results in an increase in positive ellipticity between 290 and 320 nm. Either with or without the iron, the enzyme protein binds protocatechuate and has a greater positive circular dichroism increase at 240-260 nm. CD difference spectra indicate that the modes of binding to form the binary complexes of holo- or apoenzyme with either substrates or competitive inhibitors are different. The bound iron ion stimulates binding. Spectral changes of the holoenzyme in the aromatic region were also observed in different pH environments of lower enzymatic activity. It is still not established whether these aromatic residues play an active or passive role in the binding of iron and/or substrates and inhibitors."}
{"id": "PMID:240397", "title": "Enolase catalyzed beta,gamma-alpha,beta isomerization of 2-phospho-3-butenoic acid to (Z)-phosphoenol-alpha-ketobutyrate.", "content": "2-Phospho-3-butenoic acid was synthesized and found to be a substrate for both yeast and rabbit muscle enolase (EC 4.2.1.11). Enolase catalyzes the isomerization of 2-phospho-3-butenoic acid to (Z)-phosphoenol-alpha-ketobutyrate, a beta,gamma-alpha,beta isomerization. Nuclear magnetic resonance studies on the product indicate only one isomer is formed. This reaction provides indirect evidence in further support of a carbanion intermediate for the enolase reaction. 2-Phospho-3-butenoic acid is also a good competitive inhibitor of both yeast and rabbit muscle pyruvate kinase (EC 2.7.1.40).", "contents": "Enolase catalyzed beta,gamma-alpha,beta isomerization of 2-phospho-3-butenoic acid to (Z)-phosphoenol-alpha-ketobutyrate. 2-Phospho-3-butenoic acid was synthesized and found to be a substrate for both yeast and rabbit muscle enolase (EC 4.2.1.11). Enolase catalyzes the isomerization of 2-phospho-3-butenoic acid to (Z)-phosphoenol-alpha-ketobutyrate, a beta,gamma-alpha,beta isomerization. Nuclear magnetic resonance studies on the product indicate only one isomer is formed. This reaction provides indirect evidence in further support of a carbanion intermediate for the enolase reaction. 2-Phospho-3-butenoic acid is also a good competitive inhibitor of both yeast and rabbit muscle pyruvate kinase (EC 2.7.1.40)."}
{"id": "PMID:240398", "title": "Methylation and ethylation of uridylic acid and thymidylic acid. Reactivity of the ring and phosphate as a function of pH and alkyl group.", "content": "At pH 6.8 in aqueous solution (4 hr, 22 degrees), all methylating agents tested, i.e., dimethyl sulfate, methyl methanesulfonate, and methylnitrosourea, react with both the N-3 of the ring and the phosphate of UMP and dTMP. Although the extent of reaction varies from 17 to 76%, the ratio of phosphate/ring methylation is approximately 4. Both the 3-methyl nucleotides and methyl ester of 3-methyl nucleotides are identified, as well as the methyl esters of unmodified UMP and dTMP. At pH 8.2 the extent of total methylation is similar but reactivity of the N-3 is increased and that of the phosphate decreased so that the phosphate/ring ratio is approximately 1. At pH 6 almost all reaction is with the phosphate group. Uridine, under the same conditions, is methylated at pH 6.8 to form 15% 3-methyluridine and, at pH 8.2, the N-3 of uridine and thymidine is methylated to about 50%. Neither uridine nor UMP forms detectable ribose methyl products at any of these pH's. The comparable ethylating agents (diethyl sulfate, ethyl methanesulfonate, and ethylnitrosourea) are less reactive and the total ethylation of UMP or dTMP is about 1/5 that of methylation. There is little ethylation of the N-3 but the phosphate is alkylated to a relatively high extent so that the phosphate/base ratio at pH 6.8 is 10-23, and at pH 8.2 the ratio is 5-8. The fact that ethylating agents have a greater affinity than methylating agents for alkylating phosphates is proposed as the basis for the previously reported analytical data in which ethylating agents, acting on DNA or RNA at neutrality, form more phosphotriesters than the analogous methylating agents.", "contents": "Methylation and ethylation of uridylic acid and thymidylic acid. Reactivity of the ring and phosphate as a function of pH and alkyl group. At pH 6.8 in aqueous solution (4 hr, 22 degrees), all methylating agents tested, i.e., dimethyl sulfate, methyl methanesulfonate, and methylnitrosourea, react with both the N-3 of the ring and the phosphate of UMP and dTMP. Although the extent of reaction varies from 17 to 76%, the ratio of phosphate/ring methylation is approximately 4. Both the 3-methyl nucleotides and methyl ester of 3-methyl nucleotides are identified, as well as the methyl esters of unmodified UMP and dTMP. At pH 8.2 the extent of total methylation is similar but reactivity of the N-3 is increased and that of the phosphate decreased so that the phosphate/ring ratio is approximately 1. At pH 6 almost all reaction is with the phosphate group. Uridine, under the same conditions, is methylated at pH 6.8 to form 15% 3-methyluridine and, at pH 8.2, the N-3 of uridine and thymidine is methylated to about 50%. Neither uridine nor UMP forms detectable ribose methyl products at any of these pH's. The comparable ethylating agents (diethyl sulfate, ethyl methanesulfonate, and ethylnitrosourea) are less reactive and the total ethylation of UMP or dTMP is about 1/5 that of methylation. There is little ethylation of the N-3 but the phosphate is alkylated to a relatively high extent so that the phosphate/base ratio at pH 6.8 is 10-23, and at pH 8.2 the ratio is 5-8. The fact that ethylating agents have a greater affinity than methylating agents for alkylating phosphates is proposed as the basis for the previously reported analytical data in which ethylating agents, acting on DNA or RNA at neutrality, form more phosphotriesters than the analogous methylating agents."}
{"id": "PMID:240399", "title": "DNA-dependent protein methylase activity in bull seminal plasma.", "content": "The existence of a DNA-dependent protein methylase activity without any concomitant DNA methylase activity was demonstrated in bull seminal plasma. The enzyme utilized S-adenosyl-L-methionine as a methyl donor, and endogenous seminal plasma protein as the substrate. There was no demonstrable enzyme activity when the seminal plasma was preheated at 100 degrees for 10 min, or when the enzyme reaction mixture was incubated at 4 degrees. The protein methylase required a heterologous DNA source, had optimal activity at pH 8.1, and was enhanced in the presence of Mg2+, NH4+, and reduced glutathione. After the methylated protein product was separated from DNA by extraction with 0.2 M HCl, the incorporated radioactivity was shown to be totally solubilized by incubating the protein either with Pronase or 1 M NaOH, while RNase and DNase had no effect. Approximately 70% of the enzymatically synthesized amino acids in the protein product were tentatively identified as O-methylated amino acid ethers by virtue of their elution from a Dowex 50 H+ column with 0.2 M pyridine, and their stability to acid and base hydrolysis. The partially purified methylated product was shown by Sephadex G-50 chromatography to consist of three distinct radioactive proteins with molecular weights of approximately 21,000, 15,000, and 10,000.", "contents": "DNA-dependent protein methylase activity in bull seminal plasma. The existence of a DNA-dependent protein methylase activity without any concomitant DNA methylase activity was demonstrated in bull seminal plasma. The enzyme utilized S-adenosyl-L-methionine as a methyl donor, and endogenous seminal plasma protein as the substrate. There was no demonstrable enzyme activity when the seminal plasma was preheated at 100 degrees for 10 min, or when the enzyme reaction mixture was incubated at 4 degrees. The protein methylase required a heterologous DNA source, had optimal activity at pH 8.1, and was enhanced in the presence of Mg2+, NH4+, and reduced glutathione. After the methylated protein product was separated from DNA by extraction with 0.2 M HCl, the incorporated radioactivity was shown to be totally solubilized by incubating the protein either with Pronase or 1 M NaOH, while RNase and DNase had no effect. Approximately 70% of the enzymatically synthesized amino acids in the protein product were tentatively identified as O-methylated amino acid ethers by virtue of their elution from a Dowex 50 H+ column with 0.2 M pyridine, and their stability to acid and base hydrolysis. The partially purified methylated product was shown by Sephadex G-50 chromatography to consist of three distinct radioactive proteins with molecular weights of approximately 21,000, 15,000, and 10,000."}
{"id": "PMID:240400", "title": "The possible relationship between a membrane conformational change and photosystem II dependent hydrogen ion accumulation and adenosine 5'-triphosphate synthesis.", "content": "Data are presented which suggest that photosystem II dependent hydrogen ion accumulation and ATP synthesis can occur only after the lamellar membranes have undergone a conformational change. This membrane conformational change is detected by the electron transport dependent incorporation of diazonium benzene[35S]sulfonate into membrane components. Previously it was established that electron flux from the photosystem II primary acceptor to plastoquinone is a necessary event for the occurrence of the diazonium-detected conformational change. These studies indicate that the release of hydrogen ions during photosystem II oxidation of the primary reductant is also a necessary event for the diazonium-detected conformational change. When iodide were substituted for water (or other proton-releasing donors) as the primary reductant of system II the conformational change did not occur even though a substantial rate of electron flow from the primary acceptor to plastoquinone occurred.", "contents": "The possible relationship between a membrane conformational change and photosystem II dependent hydrogen ion accumulation and adenosine 5'-triphosphate synthesis. Data are presented which suggest that photosystem II dependent hydrogen ion accumulation and ATP synthesis can occur only after the lamellar membranes have undergone a conformational change. This membrane conformational change is detected by the electron transport dependent incorporation of diazonium benzene[35S]sulfonate into membrane components. Previously it was established that electron flux from the photosystem II primary acceptor to plastoquinone is a necessary event for the occurrence of the diazonium-detected conformational change. These studies indicate that the release of hydrogen ions during photosystem II oxidation of the primary reductant is also a necessary event for the diazonium-detected conformational change. When iodide were substituted for water (or other proton-releasing donors) as the primary reductant of system II the conformational change did not occur even though a substantial rate of electron flow from the primary acceptor to plastoquinone occurred."}
{"id": "PMID:240401", "title": "Conformational studies on the beta subunits of human hemoglobin and their arginyl-COOH peptides.", "content": "The beta subunits of hemoglobin upon alkylation of the cysteinyl residues with iodoacetamide showed a sedimentation velocity with an S20w, near 1.8 as for monomeric subunits. They reacted with alpha chains to give a tetrameric hemoglobin with a sedimentation constant near 4.4. Their CD spectrum was indistinguishable from that of untreated beta chains below 270 nm, otherwise they showed some deviation that became pronounced in the Soret region, where the optical activity of the alkylated subunits was definitely lower than that of the native subunits. Upon removal of the heme the apo-beta subunits showed a decreased optical activity in the far-uv region of the spectrum indicating a substantial loss of helical content. Their sedimentation behavior was consistent with the presence of large aggregates, which dissociates into monomers upon reconstitution with cyanoheme. The apo-beta subunits could be renatured from 6 M guanidine hydrochloride. They showed a stoichiometric reaction with heme in the molar ratio 1:1. Upon reconstitution with the heme their optical activity became similar to that of the native beta chains in the far-uv region of the spectrum, but remained lower in the near-uv and Soret regions. After acylation of the lysyl residues with citraconic anhydride the apo-beta subunits were digested with trypsin and the arginyl-COOH peptides beta(1-30), beta(31-40), beta(41-104), and beta(105-146) were separated by gel chromatography. With the exception of the peptide beta/105-146), which was insoluble at neutral pH, the sedimentation behavior of the other peptides showed the presence of small polymers. The sedimentation behavior of the peptide beta(31-40) was not tested. The percentage of alpha helix, beta conformation, and of random coil (or unordered structure) of the various proteins and peptides was measured fitting their CD spectra in the far-uv region with the parameter published by Y.H. Chen et al. ((1974), Biochemistry 13, 3350) and by N. Greenfield and G.D. Fasman ((1969), Biochemistry 8, 4108). In this way the helical content of the native and reconstituted alkylated beta subunits appeared to be near 76%, a value very near to that present in the same subunits in the hemoglobin crystal. The helical content of the apo-beta subunits in 0.04 M borate buffer at pH 9.6 decreased to a value near 45%. The helical content of the isolated peptides in electrolyte solutions was in any case near 10% indicating an almost complete loss of the structure that they have in the hemoglobin crystal. Cyanoheme reacted with the peptide beta(41-104), however, the reaction was not stoichiometric indicating a low affinity of the heme for the peptide. With the exception of the peptide beta(31-104), all of the other peptides recovered some of their helical structure when dissolved in 50% methanol. Notably also the apo-beta subunits did so suggesting that the loss of structure upon the removal of the heme could be in part due to the exposure of the heme pocket to water.", "contents": "Conformational studies on the beta subunits of human hemoglobin and their arginyl-COOH peptides. The beta subunits of hemoglobin upon alkylation of the cysteinyl residues with iodoacetamide showed a sedimentation velocity with an S20w, near 1.8 as for monomeric subunits. They reacted with alpha chains to give a tetrameric hemoglobin with a sedimentation constant near 4.4. Their CD spectrum was indistinguishable from that of untreated beta chains below 270 nm, otherwise they showed some deviation that became pronounced in the Soret region, where the optical activity of the alkylated subunits was definitely lower than that of the native subunits. Upon removal of the heme the apo-beta subunits showed a decreased optical activity in the far-uv region of the spectrum indicating a substantial loss of helical content. Their sedimentation behavior was consistent with the presence of large aggregates, which dissociates into monomers upon reconstitution with cyanoheme. The apo-beta subunits could be renatured from 6 M guanidine hydrochloride. They showed a stoichiometric reaction with heme in the molar ratio 1:1. Upon reconstitution with the heme their optical activity became similar to that of the native beta chains in the far-uv region of the spectrum, but remained lower in the near-uv and Soret regions. After acylation of the lysyl residues with citraconic anhydride the apo-beta subunits were digested with trypsin and the arginyl-COOH peptides beta(1-30), beta(31-40), beta(41-104), and beta(105-146) were separated by gel chromatography. With the exception of the peptide beta/105-146), which was insoluble at neutral pH, the sedimentation behavior of the other peptides showed the presence of small polymers. The sedimentation behavior of the peptide beta(31-40) was not tested. The percentage of alpha helix, beta conformation, and of random coil (or unordered structure) of the various proteins and peptides was measured fitting their CD spectra in the far-uv region with the parameter published by Y.H. Chen et al. ((1974), Biochemistry 13, 3350) and by N. Greenfield and G.D. Fasman ((1969), Biochemistry 8, 4108). In this way the helical content of the native and reconstituted alkylated beta subunits appeared to be near 76%, a value very near to that present in the same subunits in the hemoglobin crystal. The helical content of the apo-beta subunits in 0.04 M borate buffer at pH 9.6 decreased to a value near 45%. The helical content of the isolated peptides in electrolyte solutions was in any case near 10% indicating an almost complete loss of the structure that they have in the hemoglobin crystal. Cyanoheme reacted with the peptide beta(41-104), however, the reaction was not stoichiometric indicating a low affinity of the heme for the peptide. With the exception of the peptide beta(31-104), all of the other peptides recovered some of their helical structure when dissolved in 50% methanol. Notably also the apo-beta subunits did so suggesting that the loss of structure upon the removal of the heme could be in part due to the exposure of the heme pocket to water."}
{"id": "PMID:240402", "title": "Purification and properties of an anti-B hemagglutinin produced by Streptomyces sp.", "content": "An anti-B hemagglutinin was purified to homogeneity from the culture filtrate of a strain of Streptomyces sp. by affinity chromatography. The Streptomyces hemagglutinin was adsorbed to insolubilized gum arabic and eluted with 1 M NaCl containing 1 M D-galactose. The purified hemagglutinin is thought to be homogeneous judging from sodium dodecyl sulfate-polyacrylamide gel electrophoresis at pH 7.2, disc gel electrophoresis at pH 4.3, isoelectric focusing, and ultracentrifugation. The molecular weight was estimated to be 11,000 from results of gel filtration in 6 M guanidine hydrochloride (Gdn-HCl), sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and sedimentation equilibrium analysis. The amino acid analyses revealed that the hemagglutinin contained large amounts of alanine, glycine, and valine, 47% of the total amino acid residues, and no phenylalanine. Carbohydrate analysis demonstrated that the hemagglutinin might not be a glycoprotein. The circular dichroic (CD) spectrum of the protein is quite different from those of usual proteins in having a large positive peak at 226 nm (theta = 10,000) and a negative band at 212 nm (theta =-2600). The hemagglutinin showed a typical precipitation curve with gum arabic, and agglutinated human blood group B erythrocytes 256 times as strongly as A or O erythrocytes. These activities were not affected by pH (from 4 to 12). The anti-B activity was further confirmed by serological tests. The hemagglutination-inhibition studies indicated that D-galactose was inhibitory, but alpha-D-galactosides were not necessarily better inhibitors than beta-D-galactosides. L-Rhamnose was the best inhibitor among the monosaccharides tested, and L-arabinose and D-fucose were also inhibitory.", "contents": "Purification and properties of an anti-B hemagglutinin produced by Streptomyces sp. An anti-B hemagglutinin was purified to homogeneity from the culture filtrate of a strain of Streptomyces sp. by affinity chromatography. The Streptomyces hemagglutinin was adsorbed to insolubilized gum arabic and eluted with 1 M NaCl containing 1 M D-galactose. The purified hemagglutinin is thought to be homogeneous judging from sodium dodecyl sulfate-polyacrylamide gel electrophoresis at pH 7.2, disc gel electrophoresis at pH 4.3, isoelectric focusing, and ultracentrifugation. The molecular weight was estimated to be 11,000 from results of gel filtration in 6 M guanidine hydrochloride (Gdn-HCl), sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and sedimentation equilibrium analysis. The amino acid analyses revealed that the hemagglutinin contained large amounts of alanine, glycine, and valine, 47% of the total amino acid residues, and no phenylalanine. Carbohydrate analysis demonstrated that the hemagglutinin might not be a glycoprotein. The circular dichroic (CD) spectrum of the protein is quite different from those of usual proteins in having a large positive peak at 226 nm (theta = 10,000) and a negative band at 212 nm (theta =-2600). The hemagglutinin showed a typical precipitation curve with gum arabic, and agglutinated human blood group B erythrocytes 256 times as strongly as A or O erythrocytes. These activities were not affected by pH (from 4 to 12). The anti-B activity was further confirmed by serological tests. The hemagglutination-inhibition studies indicated that D-galactose was inhibitory, but alpha-D-galactosides were not necessarily better inhibitors than beta-D-galactosides. L-Rhamnose was the best inhibitor among the monosaccharides tested, and L-arabinose and D-fucose were also inhibitory."}
{"id": "PMID:240403", "title": "Chemical accessibility of tyrosyl and lysyl residues in turnip yellow mosaic virus capsids.", "content": "The chemical accessibility of tyrosyl residues in TYMV capsids was studied by spectrophotometric titration and with the nitrating agent tetranitromethane. That of the lysyl residues was probed with trinitrobenzenesulfonate. Attempts to test their accessibility in virions were also made. Since some of these reactions were accompanied by structural changes, degradation of the particles were monitored with ultracentrifugation and light-scattering measurements. Alkaline titration of TYMV capsids induced ionization of two of the three tyrosyl residues per subunit at pH 11.3, but the third tyrosyl ionized with an apparent pK of 12.65, concomitantly with the degradation of the capsids. Reaction with tetranitromethane suggested that one tyrosyl residue per subunit can easily be nitrated and initiates degradation, after which the remaining residues also react. In intact capsids, five out of seven lysyl residues per subunit reacted readily with trinitrobenzenesulfonate. The other two lysyl residues were trinitrophenylated only after degradation of the capsids. On the other hand, all seven lysyl residues per subunit were easily trinitrophenylated in virions, during which reaction the virions disintegrated. The demonstrated  chemical inaccessibility of specific numbers of tyrosyl and lysyl residues in TYMV capsids and the observed structural consequences to the capsids when the residues were made to react are consistent with previously published properties of the cysteinyl and tryptophanyl residues. The findings suggest that in the capsid the central region of the TYMV polypeptide chain is buried and might represent a site of contact between neighboring subunits.", "contents": "Chemical accessibility of tyrosyl and lysyl residues in turnip yellow mosaic virus capsids. The chemical accessibility of tyrosyl residues in TYMV capsids was studied by spectrophotometric titration and with the nitrating agent tetranitromethane. That of the lysyl residues was probed with trinitrobenzenesulfonate. Attempts to test their accessibility in virions were also made. Since some of these reactions were accompanied by structural changes, degradation of the particles were monitored with ultracentrifugation and light-scattering measurements. Alkaline titration of TYMV capsids induced ionization of two of the three tyrosyl residues per subunit at pH 11.3, but the third tyrosyl ionized with an apparent pK of 12.65, concomitantly with the degradation of the capsids. Reaction with tetranitromethane suggested that one tyrosyl residue per subunit can easily be nitrated and initiates degradation, after which the remaining residues also react. In intact capsids, five out of seven lysyl residues per subunit reacted readily with trinitrobenzenesulfonate. The other two lysyl residues were trinitrophenylated only after degradation of the capsids. On the other hand, all seven lysyl residues per subunit were easily trinitrophenylated in virions, during which reaction the virions disintegrated. The demonstrated  chemical inaccessibility of specific numbers of tyrosyl and lysyl residues in TYMV capsids and the observed structural consequences to the capsids when the residues were made to react are consistent with previously published properties of the cysteinyl and tryptophanyl residues. The findings suggest that in the capsid the central region of the TYMV polypeptide chain is buried and might represent a site of contact between neighboring subunits."}
{"id": "PMID:240404", "title": "Bovine brain adenosine 3',5'-monophosphate dependent protein kinase. Mechanism of regulatory subunit inhibition of the catalytic subunit.", "content": "Adenosine 3',5'-monophosphate (cAMP) dependent protein kinase (EC 2.7.1.37) catalyzes the phosphorylation of serine and threonine residues of a number of proteins according to the following chemical equation: ATP + protein leads to phosphoprotein + ADP. The DEAE-cellulose peak II holoenzyme from bovine brain, which is composed of regulatory and catalytic subunits, is resistant to ethoxyformic anhydride inactivation. After adding cAMP, the protein kinase becomes susceptible to ethoxyformic anhydride inhibition. Ethoxyformic anhydride (2mM) inhibits the enzyme 50% (5 min, pH 6.5, 30 degrees) in the presence of 10 muM cAMP, but less than 5% in its absence. The substrate, Mg2+-ATP, protects against inactivation suggesting that inhibition is associated with modification of the active site. Addition of regulatory subunit or Mg2+-ATP to the isolated catalytic subunit also prevents ethoxyformic anhydride inactivation. These results suggest that the regulatory subunit shields the active site of the catalytic subunit thereby inhibiting it. In contrast to the bovine brain or muscle DEAE-cellulose peak II holoenzyme, the bovine muscle peak I holoenzyme is susceptible to ethoxyformic anhydride inactivation in the absence of cAMP.", "contents": "Bovine brain adenosine 3',5'-monophosphate dependent protein kinase. Mechanism of regulatory subunit inhibition of the catalytic subunit. Adenosine 3',5'-monophosphate (cAMP) dependent protein kinase (EC 2.7.1.37) catalyzes the phosphorylation of serine and threonine residues of a number of proteins according to the following chemical equation: ATP + protein leads to phosphoprotein + ADP. The DEAE-cellulose peak II holoenzyme from bovine brain, which is composed of regulatory and catalytic subunits, is resistant to ethoxyformic anhydride inactivation. After adding cAMP, the protein kinase becomes susceptible to ethoxyformic anhydride inhibition. Ethoxyformic anhydride (2mM) inhibits the enzyme 50% (5 min, pH 6.5, 30 degrees) in the presence of 10 muM cAMP, but less than 5% in its absence. The substrate, Mg2+-ATP, protects against inactivation suggesting that inhibition is associated with modification of the active site. Addition of regulatory subunit or Mg2+-ATP to the isolated catalytic subunit also prevents ethoxyformic anhydride inactivation. These results suggest that the regulatory subunit shields the active site of the catalytic subunit thereby inhibiting it. In contrast to the bovine brain or muscle DEAE-cellulose peak II holoenzyme, the bovine muscle peak I holoenzyme is susceptible to ethoxyformic anhydride inactivation in the absence of cAMP."}
{"id": "PMID:240405", "title": "On the role of sulfhydryl groups in the structure and function of the Azotobacter vinelandii RNA polymerase.", "content": "Exposure of sulfhydryl groups as indicated by titration kinetics is decreased under conditions where RNA polymerase exists as a dimer or higher aggregate (low salt), in the presence of Mn2+, or when bound to d(A-T). Incubation of phenylmercurisulfonate with RNA polymerase above pH 9.0 results in loss of d(A-T) binding ability. Poly(U) binding is more sensitive to sulfhydryl modification and is lost as pH's above 8.0. The presence of 4 mM Mn2+ has an obvious effect in stabilizing the polymerase-poly(U) complex when incubated with 10 muM phenylmercurisulfonate + 1 M urea. Incubation of the enzyme with the mercurial and urea results in disaggregation to subprotomeric forms and release of the alpha subunit. Similar treatment in the presence of 4 mM MnSO4 stabilizes the protomeric structure of the enzyme. During chain elongation the enzyme exists as a ternary d(A-T)n-enzyme-r(U-A)n complex in which the bound d(A-T)n is refractory to the destabilizing effect of the mercurial; however, further phosphodiester bond formation is inhibited. The results are defined in terms of a role which reflects the involvement of polymerase sulfhydryl groups in the various conformations necessary for subunit-subunit interaction, tight template binding and catalytic activity.", "contents": "On the role of sulfhydryl groups in the structure and function of the Azotobacter vinelandii RNA polymerase. Exposure of sulfhydryl groups as indicated by titration kinetics is decreased under conditions where RNA polymerase exists as a dimer or higher aggregate (low salt), in the presence of Mn2+, or when bound to d(A-T). Incubation of phenylmercurisulfonate with RNA polymerase above pH 9.0 results in loss of d(A-T) binding ability. Poly(U) binding is more sensitive to sulfhydryl modification and is lost as pH's above 8.0. The presence of 4 mM Mn2+ has an obvious effect in stabilizing the polymerase-poly(U) complex when incubated with 10 muM phenylmercurisulfonate + 1 M urea. Incubation of the enzyme with the mercurial and urea results in disaggregation to subprotomeric forms and release of the alpha subunit. Similar treatment in the presence of 4 mM MnSO4 stabilizes the protomeric structure of the enzyme. During chain elongation the enzyme exists as a ternary d(A-T)n-enzyme-r(U-A)n complex in which the bound d(A-T)n is refractory to the destabilizing effect of the mercurial; however, further phosphodiester bond formation is inhibited. The results are defined in terms of a role which reflects the involvement of polymerase sulfhydryl groups in the various conformations necessary for subunit-subunit interaction, tight template binding and catalytic activity."}
{"id": "PMID:240406", "title": "Nuclear magnetic resonance studies of residual structure in thermally unfolded ribonuclease A.", "content": "A proton nuclear magnetic resonance study of the four histidine residues of thermally unfolded ribonuclease A has provided evidence that two of the residues are in regions of residual structure, whereas the other two are freely exposed to solvent. Histidine-48 and, tentatively, histidine-105 occupy an environment at 69 degrees characterized by residual structure and display a pK value of 5.75 and a spin-lattice relaxation time of about 0.8 sec at pH 5.5. Histidine-12 and, tentatively, histidine-119 are in an environment at 69 degrees which is freely accessible to solvent and show a pK value of 5.96 and a spin-lattice relaxation time of about 1.1 sec at pH 5.5.", "contents": "Nuclear magnetic resonance studies of residual structure in thermally unfolded ribonuclease A. A proton nuclear magnetic resonance study of the four histidine residues of thermally unfolded ribonuclease A has provided evidence that two of the residues are in regions of residual structure, whereas the other two are freely exposed to solvent. Histidine-48 and, tentatively, histidine-105 occupy an environment at 69 degrees characterized by residual structure and display a pK value of 5.75 and a spin-lattice relaxation time of about 0.8 sec at pH 5.5. Histidine-12 and, tentatively, histidine-119 are in an environment at 69 degrees which is freely accessible to solvent and show a pK value of 5.96 and a spin-lattice relaxation time of about 1.1 sec at pH 5.5."}
{"id": "PMID:240407", "title": "Affinity labeling of catechol O-methyltransferase by N-haloacetyl derivatives of 3,5-dimethoxy-4-hydroxyphenylethylamine and 3,4-dimethoxy-5-hydroxyphenylethylamine. Kinetics of inactivation.", "content": "In an attempt to elucidate the relationship between the chemical structure and the catalytic function of catechol O-methyltransferase (COMT), several classes of affinity labeling reagents have been synthesized and their interaction with COMT has been studied. Earlier studies have shown that various N-haloacetyl derivatives of 3,5-dimethoxy-4-hydroxyphenylethylamine were effective affinity labeling reagents for this enzyme. In this report we have shown that N-haloacetyl derivatives of the isomeric 3,4-dimethoxy-5-hydroxyphenylethylamine also rapidly and irreversibly inactivate COMT ant they satisfy many of the criteria established for affinity labeling reagents. This latter group of agents appear to modify a nucleophilic residue at the active site of COMT different from that modified by the 3,5-dimethoxy-4-hydroxyphenylethylamine series. Evidence to support this conclusion has been obtained by comparing the kinetics of COMT inactivation and the substrate protection profiles for these two classes of affinity labeling reagents.", "contents": "Affinity labeling of catechol O-methyltransferase by N-haloacetyl derivatives of 3,5-dimethoxy-4-hydroxyphenylethylamine and 3,4-dimethoxy-5-hydroxyphenylethylamine. Kinetics of inactivation. In an attempt to elucidate the relationship between the chemical structure and the catalytic function of catechol O-methyltransferase (COMT), several classes of affinity labeling reagents have been synthesized and their interaction with COMT has been studied. Earlier studies have shown that various N-haloacetyl derivatives of 3,5-dimethoxy-4-hydroxyphenylethylamine were effective affinity labeling reagents for this enzyme. In this report we have shown that N-haloacetyl derivatives of the isomeric 3,4-dimethoxy-5-hydroxyphenylethylamine also rapidly and irreversibly inactivate COMT ant they satisfy many of the criteria established for affinity labeling reagents. This latter group of agents appear to modify a nucleophilic residue at the active site of COMT different from that modified by the 3,5-dimethoxy-4-hydroxyphenylethylamine series. Evidence to support this conclusion has been obtained by comparing the kinetics of COMT inactivation and the substrate protection profiles for these two classes of affinity labeling reagents."}
{"id": "PMID:240408", "title": "Some properties of mitochondrial glutathione.", "content": "1. The presence of GSH in rat liver mitochondria is confirmed. GSH diffuses from the suspended particles in the presence of phosphate but respiratory inhibitors inhibit the diffusion. 2. GSH is oxidised in situ by oxidants including t-butyl hydroperoxide. The products formed include GSSG and GSS-protein mixed disulphides. The oxidation occurs at lower oxidant concentrations if phosphate or oxaloacetate are also present. Respiratory inhibitors abolish their effect. 3. With phosphate, the GSSG produced is found chiefly outside the mitochondria whereas with oxaloacetate, it is found chiefly inside. 4. The GSSG formed by the oxidation is reduced by Krebs-cycle acids with the exception of the ketoacids. Exogenous GSSG is reduced by these substrates only after lysis. Intact particles, however, catalyse the reduction of GSSG by either NADH2 or NADPH2.", "contents": "Some properties of mitochondrial glutathione. 1. The presence of GSH in rat liver mitochondria is confirmed. GSH diffuses from the suspended particles in the presence of phosphate but respiratory inhibitors inhibit the diffusion. 2. GSH is oxidised in situ by oxidants including t-butyl hydroperoxide. The products formed include GSSG and GSS-protein mixed disulphides. The oxidation occurs at lower oxidant concentrations if phosphate or oxaloacetate are also present. Respiratory inhibitors abolish their effect. 3. With phosphate, the GSSG produced is found chiefly outside the mitochondria whereas with oxaloacetate, it is found chiefly inside. 4. The GSSG formed by the oxidation is reduced by Krebs-cycle acids with the exception of the ketoacids. Exogenous GSSG is reduced by these substrates only after lysis. Intact particles, however, catalyse the reduction of GSSG by either NADH2 or NADPH2."}
{"id": "PMID:240409", "title": "Studies on the binding of 1-anilino-8-naphthalene sulfonate to very low density and high density himan serum lipoproteins.", "content": "Very low density and high density lipoproteins have been isolated from human plasma and their interaction with 1-anilin0-8-naphthalene sulfonate has been studied under different conditions of pH and added salt. Intrinsic fluorescence of bound 1-anilino-8-naphthalene sulfonate was higher for high density lipoproteins then for very low density lipoproteins, but was unaffected by salt in both systems. Binding of 1-anilino-8-naphthalene sulfonate by both these lipoproteins was saturable and was higher in the presence of added NaCl or CaCl2, Ca2+ having a greater effect than Na+ in enhancing fluorescence. The binding data were analyzed by Scatchard plots; the number of binding sites and the affinity of 1-anilino-8-naphthalene sulfonate for the site increased with increasing salt concentration. Fluorescence pH curves were similar to those published for phospholipids. From these and previous observations it is suggested that the phospholipids probably represent the major binding sites for 1-anilino-8-naphthalene sulfonate.", "contents": "Studies on the binding of 1-anilino-8-naphthalene sulfonate to very low density and high density himan serum lipoproteins. Very low density and high density lipoproteins have been isolated from human plasma and their interaction with 1-anilin0-8-naphthalene sulfonate has been studied under different conditions of pH and added salt. Intrinsic fluorescence of bound 1-anilino-8-naphthalene sulfonate was higher for high density lipoproteins then for very low density lipoproteins, but was unaffected by salt in both systems. Binding of 1-anilino-8-naphthalene sulfonate by both these lipoproteins was saturable and was higher in the presence of added NaCl or CaCl2, Ca2+ having a greater effect than Na+ in enhancing fluorescence. The binding data were analyzed by Scatchard plots; the number of binding sites and the affinity of 1-anilino-8-naphthalene sulfonate for the site increased with increasing salt concentration. Fluorescence pH curves were similar to those published for phospholipids. From these and previous observations it is suggested that the phospholipids probably represent the major binding sites for 1-anilino-8-naphthalene sulfonate."}
{"id": "PMID:240410", "title": "Stimulation and inhibition of pancreatic phospholipase A2 by local anesthetics as a result of their interaction with the substrate.", "content": "1. At low concentrations the local anesthetic dibucaine stimulates hydrolysis by pancreatic phospholipase A2 of phospholipids extracted from rat liver mitochondria or microsomes, whereas at higher concentrations it inhibits. The action of this enzyme towards membrane-bound substrates is barely influenced by low, but inhibited by high concentrations of dibucaine. 2. Butacaine, which is a weaker anesthetic, stimulates hydrolysis of extracted phospholipids and inhibits that of membrane-bound substrates, both actions being concentration dependent. 3. The inhibitory potency of dibucaine is several times higher in NaCl than in sucrose solutions and strongly increases with decreasing pH. Neither one of these two effects is the result of a change in binding efficiency of the anesthetic to the substrates. 4. Extracted total membrane lipids bind considerably less anesthetic than an equivalent amount of native membrane. Liver phosphatidylethanolamine is more effective in binding of dibucaine than liver phosphatidylcholine. 5. Binding of dibucaine to the phospholipase, as studied by equilibrium dialysis is at the lower level of detectability. According to the same method dibucaine is unable to displace 45Ca2+ bound to the enzyme. 6. These results are interpreted as to support the view that local anesthetics interfere with pancreatic phospholipase activity by means of interaction with the substrate rather than with the enzyme.", "contents": "Stimulation and inhibition of pancreatic phospholipase A2 by local anesthetics as a result of their interaction with the substrate. 1. At low concentrations the local anesthetic dibucaine stimulates hydrolysis by pancreatic phospholipase A2 of phospholipids extracted from rat liver mitochondria or microsomes, whereas at higher concentrations it inhibits. The action of this enzyme towards membrane-bound substrates is barely influenced by low, but inhibited by high concentrations of dibucaine. 2. Butacaine, which is a weaker anesthetic, stimulates hydrolysis of extracted phospholipids and inhibits that of membrane-bound substrates, both actions being concentration dependent. 3. The inhibitory potency of dibucaine is several times higher in NaCl than in sucrose solutions and strongly increases with decreasing pH. Neither one of these two effects is the result of a change in binding efficiency of the anesthetic to the substrates. 4. Extracted total membrane lipids bind considerably less anesthetic than an equivalent amount of native membrane. Liver phosphatidylethanolamine is more effective in binding of dibucaine than liver phosphatidylcholine. 5. Binding of dibucaine to the phospholipase, as studied by equilibrium dialysis is at the lower level of detectability. According to the same method dibucaine is unable to displace 45Ca2+ bound to the enzyme. 6. These results are interpreted as to support the view that local anesthetics interfere with pancreatic phospholipase activity by means of interaction with the substrate rather than with the enzyme."}
{"id": "PMID:240411", "title": "Control of ketogenesis from amino acids. III. In vitro and in vivo studies on ketone body formation lipogenesis and oxidation of tyrosine by rats.", "content": "Ketone body formation from tyrosine was studied in rat liver in vitro with special references to the activities of tyrosine aminotransferse (EC 2.6.1.5)  and p-hydroxyphenylpyruvate hydroxylase (EC 1.14.2.2). Liver was obtained from rats which had been given a high protein diet or cortisol to induce various levels of tyrosine aminotransferase. The enzyme activities of the preparations were plotted against the amounts of ketone body formed from tyrosine. It was found that over a low range of tyrosine aminotransferase activities, activity was proportional to the amount of ketone body formed. However, above this range, ketone body formation ceased to increase and p-hydroxyphenylpyruvate started to accumulate. This inhibition of ketone body formation and accumulation of the p-hydroxyphenylpyruvate could be prevented by addition of ascorbate. These results suggest that the primary factor regulating metabolism of tyrosine in vitro is tyrosine aminotransferase and when the activity of this is high so that it is no longer rate limiting, p-hydroxyphenylpyruvate hydroxylase becomes the rat limiting step because its activity is inhibited by the accumulation of p-hydroxyphenylpyruvate. For in vivo studies rats were given a high protein diet or cortisol to induce various levels of tyrosine aminotransferase and then injected with a tracer dose of [U- or 1- 14C]tyrosine. Then their respiratory 14CO2 and the incorporation of 14C into total lipids of liver were measured. The amounts of radioactivity in CO2 and lipids were found to be proportional to the tyrosine aminotransferase activity and were not affected by the free tyrosine concentration in the liver. After injection of [U- 14C]acetate the radioactivities in CO2 and lipids were not proportional to the tyrosine aminotransferase activity. These results indicate that the enzyme activity also regulates tyrosine metabolism in vivo. In vivo studied gave no evidence of the participation of p-hydroxyphenylpyruvate hydroxylase in regulation of tyrosine metabolism.", "contents": "Control of ketogenesis from amino acids. III. In vitro and in vivo studies on ketone body formation lipogenesis and oxidation of tyrosine by rats. Ketone body formation from tyrosine was studied in rat liver in vitro with special references to the activities of tyrosine aminotransferse (EC 2.6.1.5)  and p-hydroxyphenylpyruvate hydroxylase (EC 1.14.2.2). Liver was obtained from rats which had been given a high protein diet or cortisol to induce various levels of tyrosine aminotransferase. The enzyme activities of the preparations were plotted against the amounts of ketone body formed from tyrosine. It was found that over a low range of tyrosine aminotransferase activities, activity was proportional to the amount of ketone body formed. However, above this range, ketone body formation ceased to increase and p-hydroxyphenylpyruvate started to accumulate. This inhibition of ketone body formation and accumulation of the p-hydroxyphenylpyruvate could be prevented by addition of ascorbate. These results suggest that the primary factor regulating metabolism of tyrosine in vitro is tyrosine aminotransferase and when the activity of this is high so that it is no longer rate limiting, p-hydroxyphenylpyruvate hydroxylase becomes the rat limiting step because its activity is inhibited by the accumulation of p-hydroxyphenylpyruvate. For in vivo studies rats were given a high protein diet or cortisol to induce various levels of tyrosine aminotransferase and then injected with a tracer dose of [U- or 1- 14C]tyrosine. Then their respiratory 14CO2 and the incorporation of 14C into total lipids of liver were measured. The amounts of radioactivity in CO2 and lipids were found to be proportional to the tyrosine aminotransferase activity and were not affected by the free tyrosine concentration in the liver. After injection of [U- 14C]acetate the radioactivities in CO2 and lipids were not proportional to the tyrosine aminotransferase activity. These results indicate that the enzyme activity also regulates tyrosine metabolism in vivo. In vivo studied gave no evidence of the participation of p-hydroxyphenylpyruvate hydroxylase in regulation of tyrosine metabolism."}
{"id": "PMID:240412", "title": "13C-nuclear magnetic resonance studies of 85% 13C-enriched amino acids and small peptides. pH effects on the chemical shifts, coupling constants, kinetics of cis-trans isomerisation and conformation aspects.", "content": "The 13C chemical shifts of several 85% 13C-enriched amino acids and small peptides were studied as a function of pH. The results show that the chemical shifts of carbon atoms of ionizable groups vary significantly within the zone of their pK. Generally with the pH GOING FROM 7 to 1 all the deltaC are shifted more or less upfield with the exception of the carbonyl group carbon of the second last residue which is shifted slightly downfield. This suggests the formation of an hydrogen bond at acid pH involving in a seven-membered ring the C=O in question and the COOH terminal. The percentage of cis and trans conformers of glycyl-L-proline and glycyl-L-prolylglycine were studied as a function of pH. The trans form is always preponderant whatever the pH. The accessibility of the carbonyl group to protonation of the proline residue strongly influences the cis-trans equilibrium. Thus, with the pH varying from 7 to 1, the trans isomer changes from 61 to 85% for glycyl-L-proline and only from 77 to 80% for glycyl-L-prolylglycine. The proton NMR studies underline the important differences existing between the two molecular forms of glycyl-L-proline. The cis conformation is characterized with regard to the trans form by the non-equivalence of the alpha-protons of the glycine residue, by a lower pK(1) and by a larger deltadeltaHalpha of the proline residue as a function of pH. These results could suggest an end-to-end interaction in the cis form of the glycyl-L-proline molecule. The 13C-13C coupling constants were also studied as a function of pH. The results show that J(Co-Calpha) of a C-terminal residue, varying from 5 to 6 Hz and reflecting thhe pK of the carboxylate group, is a linear function of delta(Co) and delta(Calpha) as in the case of the amino acids. The total variation of the electron density of those two carbons in an amino acid is approximately 40% weaker than in a C-terminal residue. The charge distribution along the Calpha-C(o) bond, however, is practically the same in both cases. Finally the ratios of the conversion rate constants of the two isomers cis-trans of glycyl-proline were calculated at different pH values; the relations between the isomer percentages and delta(Co), delta(Calpha) on the one hand and the J(Co-Calpha) on the other were established.", "contents": "13C-nuclear magnetic resonance studies of 85% 13C-enriched amino acids and small peptides. pH effects on the chemical shifts, coupling constants, kinetics of cis-trans isomerisation and conformation aspects. The 13C chemical shifts of several 85% 13C-enriched amino acids and small peptides were studied as a function of pH. The results show that the chemical shifts of carbon atoms of ionizable groups vary significantly within the zone of their pK. Generally with the pH GOING FROM 7 to 1 all the deltaC are shifted more or less upfield with the exception of the carbonyl group carbon of the second last residue which is shifted slightly downfield. This suggests the formation of an hydrogen bond at acid pH involving in a seven-membered ring the C=O in question and the COOH terminal. The percentage of cis and trans conformers of glycyl-L-proline and glycyl-L-prolylglycine were studied as a function of pH. The trans form is always preponderant whatever the pH. The accessibility of the carbonyl group to protonation of the proline residue strongly influences the cis-trans equilibrium. Thus, with the pH varying from 7 to 1, the trans isomer changes from 61 to 85% for glycyl-L-proline and only from 77 to 80% for glycyl-L-prolylglycine. The proton NMR studies underline the important differences existing between the two molecular forms of glycyl-L-proline. The cis conformation is characterized with regard to the trans form by the non-equivalence of the alpha-protons of the glycine residue, by a lower pK(1) and by a larger deltadeltaHalpha of the proline residue as a function of pH. These results could suggest an end-to-end interaction in the cis form of the glycyl-L-proline molecule. The 13C-13C coupling constants were also studied as a function of pH. The results show that J(Co-Calpha) of a C-terminal residue, varying from 5 to 6 Hz and reflecting thhe pK of the carboxylate group, is a linear function of delta(Co) and delta(Calpha) as in the case of the amino acids. The total variation of the electron density of those two carbons in an amino acid is approximately 40% weaker than in a C-terminal residue. The charge distribution along the Calpha-C(o) bond, however, is practically the same in both cases. Finally the ratios of the conversion rate constants of the two isomers cis-trans of glycyl-proline were calculated at different pH values; the relations between the isomer percentages and delta(Co), delta(Calpha) on the one hand and the J(Co-Calpha) on the other were established."}
{"id": "PMID:240413", "title": "Induction of multiple forms of tyrosine aminotransferase by amino acid mixtures of different compositions.", "content": "Hepatic tyrosine aminotransferase (EC 2.6.1.5) was induced in rats by intubation of amino acid mixtures (complete or tryptophan-free). Enzyme activity was increased 4-fold by the complete mixture and 8-fold by the tryptophan-free mixture. The enzyme was analyzed by chromatography on CM-Sephadex. Chromatographic patterns were characteristic of the type of inducer rather than of the chronology of the induction cycle: after induction by the complete amino acid mixture the three forms of the enzyme were equally increased whereas after induction by the tryptophan-free mixture Form I was preferentially increased.", "contents": "Induction of multiple forms of tyrosine aminotransferase by amino acid mixtures of different compositions. Hepatic tyrosine aminotransferase (EC 2.6.1.5) was induced in rats by intubation of amino acid mixtures (complete or tryptophan-free). Enzyme activity was increased 4-fold by the complete mixture and 8-fold by the tryptophan-free mixture. The enzyme was analyzed by chromatography on CM-Sephadex. Chromatographic patterns were characteristic of the type of inducer rather than of the chronology of the induction cycle: after induction by the complete amino acid mixture the three forms of the enzyme were equally increased whereas after induction by the tryptophan-free mixture Form I was preferentially increased."}
{"id": "PMID:240414", "title": "Membrane-bound potassium and magnesium ion-stimulated inorganic pyrophosphatase from roots and cotyledons of sugar beet (Beta vulgaris L).", "content": "1. The 25 000-30 000 X g fraction from sugar beet leaf or roots contains, together with (Na+ plus K+)-activated ATPase, also K+-stimulated inorganic pyrophosphatase. 2. This inorganic pyrophosphatase is also stimulated by Rb+ and to a lesser degree by Li+ and Na+. 3. Na+ is at the same time an inhibitor to the K+-stimulation of the inorganic pyrophosphatase. 4. No signs of synergism for (Na+ plus K+) were found. 5. Optimum pH was at about 8.5.", "contents": "Membrane-bound potassium and magnesium ion-stimulated inorganic pyrophosphatase from roots and cotyledons of sugar beet (Beta vulgaris L). 1. The 25 000-30 000 X g fraction from sugar beet leaf or roots contains, together with (Na+ plus K+)-activated ATPase, also K+-stimulated inorganic pyrophosphatase. 2. This inorganic pyrophosphatase is also stimulated by Rb+ and to a lesser degree by Li+ and Na+. 3. Na+ is at the same time an inhibitor to the K+-stimulation of the inorganic pyrophosphatase. 4. No signs of synergism for (Na+ plus K+) were found. 5. Optimum pH was at about 8.5."}
{"id": "PMID:240415", "title": "Purification of hog renin by affinity chromatography using the synthetic competitive inhibitor (D-Leu6)octapeptide.", "content": "The renin substrate analog His-Pro-Phe-His-Leu-D-Leu-Val-Tyr ([D-Leu6]-octapeptide) acts as a potent inhibitor of renin because of the D-amino acid substitution at the cleavage site. This inhibitor was coupled to CNBr-activated Sepharose 4B to yield a support for affinity chromatography. Hog renin with a specific activity of 1.2 Goldblatt units/mg was in one step purified 195-fold to a final specific activity of 234 Goldblatt units/mg. Application of a pH gradient from 5.0 to 7.5 to the support was found to be the most successful elution program, probably because the [D-Leu6]-octapeptide is not an inhibitor for renin at neutral pH.", "contents": "Purification of hog renin by affinity chromatography using the synthetic competitive inhibitor (D-Leu6)octapeptide. The renin substrate analog His-Pro-Phe-His-Leu-D-Leu-Val-Tyr ([D-Leu6]-octapeptide) acts as a potent inhibitor of renin because of the D-amino acid substitution at the cleavage site. This inhibitor was coupled to CNBr-activated Sepharose 4B to yield a support for affinity chromatography. Hog renin with a specific activity of 1.2 Goldblatt units/mg was in one step purified 195-fold to a final specific activity of 234 Goldblatt units/mg. Application of a pH gradient from 5.0 to 7.5 to the support was found to be the most successful elution program, probably because the [D-Leu6]-octapeptide is not an inhibitor for renin at neutral pH."}
{"id": "PMID:240416", "title": "Assignment of the imidazole ring nitrogen protons of histidine 48 in the proton NMR spectrum of ribonuclease A in water solution.", "content": "Several exchangeable resonances, designated a, b, c and d are observed in the 11-14 ppm (from 2,2-dimethyl-2-silapentane-5-sulfonate) region of the proton spectrum of ribonuclease A in water solution. We describe a number of lines of evidence suggesting the assignment of peaks b and c to the N1 and N3 protons of His 48, which occupies an interior position in the protein remote from the active site. This evidence includes the observation that the binding of Cu(II) and 3'-CMP (cytidine 3'-monophosphate) has no effect on these resonances. Further evidence includes pH titration data showing a pKa of approx. 2 for these protons, solvent exchange rates in the native state and with disulfide bridges IV-V and III-VIII cleaved, the observation of the carboxymethylated enzymes CM-His12-RNAase A and CM-His119-RNAase A, and of the modified enzymes Des(1-21)-RNAase A (S-protein) and Des(119-124)-RNAase A.", "contents": "Assignment of the imidazole ring nitrogen protons of histidine 48 in the proton NMR spectrum of ribonuclease A in water solution. Several exchangeable resonances, designated a, b, c and d are observed in the 11-14 ppm (from 2,2-dimethyl-2-silapentane-5-sulfonate) region of the proton spectrum of ribonuclease A in water solution. We describe a number of lines of evidence suggesting the assignment of peaks b and c to the N1 and N3 protons of His 48, which occupies an interior position in the protein remote from the active site. This evidence includes the observation that the binding of Cu(II) and 3'-CMP (cytidine 3'-monophosphate) has no effect on these resonances. Further evidence includes pH titration data showing a pKa of approx. 2 for these protons, solvent exchange rates in the native state and with disulfide bridges IV-V and III-VIII cleaved, the observation of the carboxymethylated enzymes CM-His12-RNAase A and CM-His119-RNAase A, and of the modified enzymes Des(1-21)-RNAase A (S-protein) and Des(119-124)-RNAase A."}
{"id": "PMID:240417", "title": "Plasmic degradation of bovine fibrinogen and non-crosslinked fibrins in solution and in gel form.", "content": "1. Analysis of degradation processes of bovine fibrinogen by bovine plasmin using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and a study on the mode of changes of the properties related to clotting of digestion products as a function of time were performed. Gross features and patterns very similar to those which had been reported with human fibrinogen-plasmin systems were obtained. 2. Based on the molecular size of the degradation products and the mode of appearance and disappearance of the degradation products, the processes could tentatively be divided into three stages: stage 1, where fibrinogen (mol. wt 370 000) was degraded to produce fragments X1 (330 000) and X2 (290 000); stage 2, fragment X2 was degraded with appearance of Y (210 000) and D1 (140 000); stage 3, appearance of fragments D1, D2 (110 000), and D3 (100 000) sequentially and E (68 000) with concomitant disappearance of Y. 3. A microseparation method, which is a combination of dansylation and sodium dodecylsulfate-polyacrylamide gel electrophoresis, was devised to analyze the events of stage 1 in detail, and a molecular model for the process was proposed. 4. The plasmic degradation processes of bovine non-cross-linked fibrins in solution and in gel form were compared with that of fibrinogen and it was found that the state of the substrates, fibrins, could cause differences in the degradation patterns. With the former substrate, essentially the same sodium dodecyl sulfate-polyacrylamide gel electrophoretic patterns as those with fibrinogen were obtained. With the latter substrate, however, a distinct difference in the mode of degradation of beta chains was observed.", "contents": "Plasmic degradation of bovine fibrinogen and non-crosslinked fibrins in solution and in gel form. 1. Analysis of degradation processes of bovine fibrinogen by bovine plasmin using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and a study on the mode of changes of the properties related to clotting of digestion products as a function of time were performed. Gross features and patterns very similar to those which had been reported with human fibrinogen-plasmin systems were obtained. 2. Based on the molecular size of the degradation products and the mode of appearance and disappearance of the degradation products, the processes could tentatively be divided into three stages: stage 1, where fibrinogen (mol. wt 370 000) was degraded to produce fragments X1 (330 000) and X2 (290 000); stage 2, fragment X2 was degraded with appearance of Y (210 000) and D1 (140 000); stage 3, appearance of fragments D1, D2 (110 000), and D3 (100 000) sequentially and E (68 000) with concomitant disappearance of Y. 3. A microseparation method, which is a combination of dansylation and sodium dodecylsulfate-polyacrylamide gel electrophoresis, was devised to analyze the events of stage 1 in detail, and a molecular model for the process was proposed. 4. The plasmic degradation processes of bovine non-cross-linked fibrins in solution and in gel form were compared with that of fibrinogen and it was found that the state of the substrates, fibrins, could cause differences in the degradation patterns. With the former substrate, essentially the same sodium dodecyl sulfate-polyacrylamide gel electrophoretic patterns as those with fibrinogen were obtained. With the latter substrate, however, a distinct difference in the mode of degradation of beta chains was observed."}
{"id": "PMID:240418", "title": "Hemoglobin Cochin-Port-Royal: consequences of the replacement of the beta chain C-terminal by an arginine.", "content": "Hemoglobin Cochin Port-Royal beta 146 (HC3) His yields Arg is the second example in which the beta C-terminal residue is replaced. Owing to the known importance of His beta 146 in the co-operative effects of hemoglobin, the functional properties of this variant were carefully studied. It had a normal Hill coefficient but a reduced alkaline Bohr effect. However, the reduction in Bohr effect is less than the halving predicted from previous mutants and modified hemoglobins.", "contents": "Hemoglobin Cochin-Port-Royal: consequences of the replacement of the beta chain C-terminal by an arginine. Hemoglobin Cochin Port-Royal beta 146 (HC3) His yields Arg is the second example in which the beta C-terminal residue is replaced. Owing to the known importance of His beta 146 in the co-operative effects of hemoglobin, the functional properties of this variant were carefully studied. It had a normal Hill coefficient but a reduced alkaline Bohr effect. However, the reduction in Bohr effect is less than the halving predicted from previous mutants and modified hemoglobins."}
{"id": "PMID:240419", "title": "The thiol group of bovine serum albumin. High reactivity at acidic pH as measured by the reaction with 2,2'-dipyridyl disulphide.", "content": "The reaction between 2,2'-dipyridyl disulphide and the thiol group in bovine serum albumin has been studied at pH 1.1-7.9. At pH 5.5-7.9 the reaction rate was second order in dipyridyl disulphide and thiolate ion, as expected for an aliphatic thiol compound. Below pH 5.5 the reaction rate increased and became maximum at pH 2.6. The observed rate constant (110 M-1-s-1) was comparable with that at pH 6.6, although the thiolate ion concentration should be 10(4) times less at the lower pH. The increase in reactivity seemed to be correlated with the conformational change in serum albumin at pH 3.6-4.0. Increased nucleophilicity due to interaction with some suitable functional group might explain the high reactivity of the SH group at acidic pH.", "contents": "The thiol group of bovine serum albumin. High reactivity at acidic pH as measured by the reaction with 2,2'-dipyridyl disulphide. The reaction between 2,2'-dipyridyl disulphide and the thiol group in bovine serum albumin has been studied at pH 1.1-7.9. At pH 5.5-7.9 the reaction rate was second order in dipyridyl disulphide and thiolate ion, as expected for an aliphatic thiol compound. Below pH 5.5 the reaction rate increased and became maximum at pH 2.6. The observed rate constant (110 M-1-s-1) was comparable with that at pH 6.6, although the thiolate ion concentration should be 10(4) times less at the lower pH. The increase in reactivity seemed to be correlated with the conformational change in serum albumin at pH 3.6-4.0. Increased nucleophilicity due to interaction with some suitable functional group might explain the high reactivity of the SH group at acidic pH."}
{"id": "PMID:240420", "title": "Inactivation of biologically active DNA by gamma-ray-induced superoxide radicals and their dismutation products singlet molecular oxygen and hydrogen peroxide.", "content": "Since superoxide radicals are involved in many metabolically important as well as in some other, detrimental cellular processes, the reactivity of gamma-ray-induced superoxide radicals and its dismutation products singlet molecular oxygen and hydrogen peroxide with DNA have been studied. Superoxide dismutase which removes superoxide radicals and inhibits the formation of singlet oxygen in the solution protects the biologically active replicative form of DNA (from bacteriophage theta X174) against inactivation by ionizing radiation. Catalase which removes hydrogen peroxide also protects the DNA. Attempts with various chemical sources of singlet oxygen to determine whether this species inactivates DNA did not give an unequivocal answer. It is concluded from the presented experiments that a combination of the protonated form of the superoxide radical (HO-2) and H2O2 do inactivate DNA.", "contents": "Inactivation of biologically active DNA by gamma-ray-induced superoxide radicals and their dismutation products singlet molecular oxygen and hydrogen peroxide. Since superoxide radicals are involved in many metabolically important as well as in some other, detrimental cellular processes, the reactivity of gamma-ray-induced superoxide radicals and its dismutation products singlet molecular oxygen and hydrogen peroxide with DNA have been studied. Superoxide dismutase which removes superoxide radicals and inhibits the formation of singlet oxygen in the solution protects the biologically active replicative form of DNA (from bacteriophage theta X174) against inactivation by ionizing radiation. Catalase which removes hydrogen peroxide also protects the DNA. Attempts with various chemical sources of singlet oxygen to determine whether this species inactivates DNA did not give an unequivocal answer. It is concluded from the presented experiments that a combination of the protonated form of the superoxide radical (HO-2) and H2O2 do inactivate DNA."}
{"id": "PMID:240421", "title": "Differentiation and characterization of the cytoplasmic and nuclear deoxyribonucleic acid polymerases from baby hamster kidney cells.", "content": "Distinct DNA polymerase activities have been found in the cytoplasmic and nuclear fractions of a baby hamster kidney cell line. They were separated by chromatography on DEAE-cellulose and partially purified by ammonium sulfate fractionation, DNA - cellulose and linear sucrose gradients. The cytoplasmic DNA polymerase exhibited an S-coefficient of 6.95 S in 0.15 M NaCl and its activity was highly sensitive to inhibition by N-ethylmaleimide and elevated temperatures, regardless of the presence of DNA template or other cofactors. It was stimulated by monovalent salts in the order of NH4 Cl greater than KCl greater than NaCl greater than CsCl greater than LiCl (inhibitory). The DNA polymerase extracted from nuclei sedimented with an S-value of 3.47 S, was resistant to inactivation by N-ethylmaleimide, and maximally stimulated by NaCl, while also being inhibited by LiCl. For optimal activity, both DNA polymerase activities required a divalent cation, with MgCl2 being more effective than MnCl2. Although the optimal pH values for the two enzyme activities differed slightly, glycine - NaOH buffer induced an alkaline shift of 1.5 pH units in the optimum of both enzymes. This was accompanied by an increase in the effectiveness of MnCl2 relative to MgCl2 for the cytoplasmic DNA polymerase.", "contents": "Differentiation and characterization of the cytoplasmic and nuclear deoxyribonucleic acid polymerases from baby hamster kidney cells. Distinct DNA polymerase activities have been found in the cytoplasmic and nuclear fractions of a baby hamster kidney cell line. They were separated by chromatography on DEAE-cellulose and partially purified by ammonium sulfate fractionation, DNA - cellulose and linear sucrose gradients. The cytoplasmic DNA polymerase exhibited an S-coefficient of 6.95 S in 0.15 M NaCl and its activity was highly sensitive to inhibition by N-ethylmaleimide and elevated temperatures, regardless of the presence of DNA template or other cofactors. It was stimulated by monovalent salts in the order of NH4 Cl greater than KCl greater than NaCl greater than CsCl greater than LiCl (inhibitory). The DNA polymerase extracted from nuclei sedimented with an S-value of 3.47 S, was resistant to inactivation by N-ethylmaleimide, and maximally stimulated by NaCl, while also being inhibited by LiCl. For optimal activity, both DNA polymerase activities required a divalent cation, with MgCl2 being more effective than MnCl2. Although the optimal pH values for the two enzyme activities differed slightly, glycine - NaOH buffer induced an alkaline shift of 1.5 pH units in the optimum of both enzymes. This was accompanied by an increase in the effectiveness of MnCl2 relative to MgCl2 for the cytoplasmic DNA polymerase."}
{"id": "PMID:240422", "title": "Cyclic nucleotide phosphodiesterase in silkworm. Developmental change of cyclic AMP and cyclic GMP phosphodiesterases.", "content": "Changes in theactivities of two cyclic AMP phosphodiesterases (II and III, EC 3.1.4.17) and cyclic GMP phosphodiesterase during development were studied in silkworm, Bombyx mori. The developmental patterns of the activities of the two cyclic AMP phosphodiesterases were similar to each other, but they differed distinctly from that of cyclic GMP phosphodiesterase. The ratios of cyclic GMP phosphodiesterase/cyclic AMP phosphodiesterase III were constant in larva, but changed greatly and rapidly before pupation.", "contents": "Cyclic nucleotide phosphodiesterase in silkworm. Developmental change of cyclic AMP and cyclic GMP phosphodiesterases. Changes in theactivities of two cyclic AMP phosphodiesterases (II and III, EC 3.1.4.17) and cyclic GMP phosphodiesterase during development were studied in silkworm, Bombyx mori. The developmental patterns of the activities of the two cyclic AMP phosphodiesterases were similar to each other, but they differed distinctly from that of cyclic GMP phosphodiesterase. The ratios of cyclic GMP phosphodiesterase/cyclic AMP phosphodiesterase III were constant in larva, but changed greatly and rapidly before pupation."}
{"id": "PMID:240423", "title": "Purification, properties and glycoprotein nature of arylsulfatase A from sheep brain.", "content": "A simple and rapid method for the purification of arylsulfatase A (EC 3.1.6.1) from sheep brain has been developed. This includes the concanavalin A-Sepharose affinity chromatography and the pH-dependent polymerization and depolymerization of the enzyme. By these methods a homogeneous enzyme was obtained and the enzyme was purified 7180-fold. Sheep brain arylsulfatase A has been shown to be a glycoprotein containing 25% neutral sugar and 0.5% sialic acid. The constituent neutral sugars were identified as glucose and mannose.", "contents": "Purification, properties and glycoprotein nature of arylsulfatase A from sheep brain. A simple and rapid method for the purification of arylsulfatase A (EC 3.1.6.1) from sheep brain has been developed. This includes the concanavalin A-Sepharose affinity chromatography and the pH-dependent polymerization and depolymerization of the enzyme. By these methods a homogeneous enzyme was obtained and the enzyme was purified 7180-fold. Sheep brain arylsulfatase A has been shown to be a glycoprotein containing 25% neutral sugar and 0.5% sialic acid. The constituent neutral sugars were identified as glucose and mannose."}
{"id": "PMID:240424", "title": "Purification and properties of alpha,alpha-trehalase from the mucosa of rat small intestine.", "content": "ALPHA,ALPHA-Trehalase (EC 3.2.1.28, alpha,alpha-trehalose glucohydrolase) was solubilized from the microvillous membrane of the intestinal mucosa of rats with Triton X-100 and butanol. It was purified 6350-fold by gel filtration on Sephadex G-150 and chromatography on DE-52 and hydroxyapatite. The purified enzyme, with a specific activity of about 127 units per mg of protein, showed almost a single band of protein and activity on polyacrylamide gel electrophoresis. Its molecular weight was estimated to be 96 000 on Sephadex G-150 and 90 000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Its pH optimum was 5.5-5.7 and its Km value for trehalose was 5.4 mM. Its activity was inhibited 30 and 100% by 1 mM p-chloromercuribenzoate and 0.1 mM HgCl2, respectively and 30% by 1 mM MgCl2. Moreover, its activity was inhibited completely by 10 mM tris(hydroxymethyl)aminomethane and about 60% by 10 mM sucrose and cellobiose. The enzyme showed a high specificity for trehalose.", "contents": "Purification and properties of alpha,alpha-trehalase from the mucosa of rat small intestine. ALPHA,ALPHA-Trehalase (EC 3.2.1.28, alpha,alpha-trehalose glucohydrolase) was solubilized from the microvillous membrane of the intestinal mucosa of rats with Triton X-100 and butanol. It was purified 6350-fold by gel filtration on Sephadex G-150 and chromatography on DE-52 and hydroxyapatite. The purified enzyme, with a specific activity of about 127 units per mg of protein, showed almost a single band of protein and activity on polyacrylamide gel electrophoresis. Its molecular weight was estimated to be 96 000 on Sephadex G-150 and 90 000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Its pH optimum was 5.5-5.7 and its Km value for trehalose was 5.4 mM. Its activity was inhibited 30 and 100% by 1 mM p-chloromercuribenzoate and 0.1 mM HgCl2, respectively and 30% by 1 mM MgCl2. Moreover, its activity was inhibited completely by 10 mM tris(hydroxymethyl)aminomethane and about 60% by 10 mM sucrose and cellobiose. The enzyme showed a high specificity for trehalose."}
{"id": "PMID:240425", "title": "Intestinal surface peptide hydrolases: identification and characterization of three enzymes from rat brush border.", "content": "Peptide hydrolases were solubilized from rat small intestinal brush border by papain and separated by Sephadex G-200 chromatography, velocity gradient ultracentrifugation and polyacrylamide disc electrophoresis and designated according to approximate molecular size from sedimentation studies. Peptidases I (apparent Mr 230 000) and II (apparent Mr 160 000) are oligopeptidases with maximum specificity for tripeptides with identical pH optima (7.5) and similar apparent Km with L-Leu-Gly (I, 0.60 MM; II, 0.76 mM). L-Leucyl-beta-naphthylamide is a competitive inhibitor of both enzymes. Concentration of peptidase II produced partial conversion to peptidase I on polyacrylamide disc electrophoresis. The third peptide hydrolase (III, Mr 120 000) is a dipeptidase with pH optimum 8.5 and apparent Km for L-Leu-Gly of 0.65 mM. These peptide hydrolases were inhibited appreciably (37-59%) by 0.2 M glycine/NaOH, Tris - HCl or Tris - glycine buffers. EDTA (5 mM) completely inhibited these enzymes but all activity was restored by dialysis against buffer without divalent ions. Subsequent addition of Mg2+, Mn2+, Co2+ or Zn2+ (1-2 mM) inhibited peptidases I and II variably (4-81%) depending upon the substrate and buffer used. In contrast peptidase III was activated slightly by metal ions (5-20%). These peptide hydrolases are strategically located at the intestinal lumen-cell interface and possess biochemical characteristics making them ideally suited to play a pivotal role in the final stage of protein digestion.", "contents": "Intestinal surface peptide hydrolases: identification and characterization of three enzymes from rat brush border. Peptide hydrolases were solubilized from rat small intestinal brush border by papain and separated by Sephadex G-200 chromatography, velocity gradient ultracentrifugation and polyacrylamide disc electrophoresis and designated according to approximate molecular size from sedimentation studies. Peptidases I (apparent Mr 230 000) and II (apparent Mr 160 000) are oligopeptidases with maximum specificity for tripeptides with identical pH optima (7.5) and similar apparent Km with L-Leu-Gly (I, 0.60 MM; II, 0.76 mM). L-Leucyl-beta-naphthylamide is a competitive inhibitor of both enzymes. Concentration of peptidase II produced partial conversion to peptidase I on polyacrylamide disc electrophoresis. The third peptide hydrolase (III, Mr 120 000) is a dipeptidase with pH optimum 8.5 and apparent Km for L-Leu-Gly of 0.65 mM. These peptide hydrolases were inhibited appreciably (37-59%) by 0.2 M glycine/NaOH, Tris - HCl or Tris - glycine buffers. EDTA (5 mM) completely inhibited these enzymes but all activity was restored by dialysis against buffer without divalent ions. Subsequent addition of Mg2+, Mn2+, Co2+ or Zn2+ (1-2 mM) inhibited peptidases I and II variably (4-81%) depending upon the substrate and buffer used. In contrast peptidase III was activated slightly by metal ions (5-20%). These peptide hydrolases are strategically located at the intestinal lumen-cell interface and possess biochemical characteristics making them ideally suited to play a pivotal role in the final stage of protein digestion."}
{"id": "PMID:240426", "title": "Macrophage esterase: identification, purification and properties of a chymotrypsin-like esterase from lung that hydrolyses and transfers nonpolar amino acid esters.", "content": "A chymotrypsin-like esterase was purified from beef lung. This lysosomal enzyme, not previously characterized, seemed to be composed of two or more forms with molecular weights of about 52 000. It hydrolysed N-benzoyl-DL-phenylalanine beta-naphthol ester at acid and neutral pH; it polymerized L-phenylalanine methyl ester(Phe-OMe) at neutral pH; and it transferred the Phe-residue from Phe-OMe to hydroxylamine at neutral pH. Phenylmethanesulfonyl fluoride, an inhibitor of hydrolytic enzymes with serine in their catalytic site, inhibited this enzyme, but pepstatin, the cathepsin D (EC 3.4.4.23) inhibitor, did not. Sulfhydryl reagents were not required for activity. Macrophages, especially pulmonary alveolar macrophages, were a rich source of this esterase, so it is likely that the enzyme purified from lung came from its macrophages. The esterase hydrolysed and transferred monoamino acid esters, especially those of the aromatic type. Cathepsin C, the dipeptidyl peptide hydrolase (EC 3.4.14.1), acted only on dipeptide esters and amides. Pancreatic chymotrypsin acted on both monoamino acid and dipeptide esters. The chymotrypsin-like esterase did not hydrolyse hemoglobin, casein, or plasma albumin. Thus its proteolytic activity, if present, must be limited to specific substrates, as yet unknown.", "contents": "Macrophage esterase: identification, purification and properties of a chymotrypsin-like esterase from lung that hydrolyses and transfers nonpolar amino acid esters. A chymotrypsin-like esterase was purified from beef lung. This lysosomal enzyme, not previously characterized, seemed to be composed of two or more forms with molecular weights of about 52 000. It hydrolysed N-benzoyl-DL-phenylalanine beta-naphthol ester at acid and neutral pH; it polymerized L-phenylalanine methyl ester(Phe-OMe) at neutral pH; and it transferred the Phe-residue from Phe-OMe to hydroxylamine at neutral pH. Phenylmethanesulfonyl fluoride, an inhibitor of hydrolytic enzymes with serine in their catalytic site, inhibited this enzyme, but pepstatin, the cathepsin D (EC 3.4.4.23) inhibitor, did not. Sulfhydryl reagents were not required for activity. Macrophages, especially pulmonary alveolar macrophages, were a rich source of this esterase, so it is likely that the enzyme purified from lung came from its macrophages. The esterase hydrolysed and transferred monoamino acid esters, especially those of the aromatic type. Cathepsin C, the dipeptidyl peptide hydrolase (EC 3.4.14.1), acted only on dipeptide esters and amides. Pancreatic chymotrypsin acted on both monoamino acid and dipeptide esters. The chymotrypsin-like esterase did not hydrolyse hemoglobin, casein, or plasma albumin. Thus its proteolytic activity, if present, must be limited to specific substrates, as yet unknown."}
{"id": "PMID:240427", "title": "Pepsin immobilized by covalent fixation to hydroxyalkyl methacrylate gels: preparation and characterization.", "content": "Insoluble active derivatives of pepsin (EC 3.4.23.1) were prepared by covalent binding of this enzyme to hydroxyalkyl methacrylate gels modified with 1,6-diaminohexane or epsilon-aminocaproic acid in an acid medium by means of water-soluble carbodiimide. The amount of attached enzyme, its proteolytic activity, pH activity curves of the preparations obtained and the time and pH dependence of their stability were determined.", "contents": "Pepsin immobilized by covalent fixation to hydroxyalkyl methacrylate gels: preparation and characterization. Insoluble active derivatives of pepsin (EC 3.4.23.1) were prepared by covalent binding of this enzyme to hydroxyalkyl methacrylate gels modified with 1,6-diaminohexane or epsilon-aminocaproic acid in an acid medium by means of water-soluble carbodiimide. The amount of attached enzyme, its proteolytic activity, pH activity curves of the preparations obtained and the time and pH dependence of their stability were determined."}
{"id": "PMID:240428", "title": "Studies of homogeneous \"biosynthetic\" L-threonine dehydratase from Escherichia coli K-12. Some kinetic properties and molecular multiplicity.", "content": "\"Biosynthetic\" L-threonine dehydratase (EC 4.2.1.16) was purified to a homogeneous state with 29% yield of total activity from Escherichia coli K-12. The homogeneity of the enzyme was shown by polyacrylamide gel disc electrophoresis in the presence of dodecyl sulphate. The enzyme consisted of equal subunits having a molecular weight of about 57 000. The polyacrylamide gel disc electrophoresis has shown that the native enzyme consisted of a set of oligomeric forms. The multiplicity of molecular organization of the enzyme was reflected in complicated kinetic behaviour: at pH greater than 9 on the plots of initial reaction rate (v) versus initial substrate concentration ([S]o) there were four inflexion points (two intermediate plateaux), the position and deepness of which depended on enzyme concentration. At pH 8.3 on the v versus [S]o plots appeared two inflexion points (one intermediate plateu), the position of which practically did not depend on enzyme concentration in the reaction mixture, but strongly depended on the enzyme concentration in the stock solution. Repeated polyacrylamide gel disc electrophoresis of several oligomeric forms, isolated by the first electrophoresis, has shown that the oligomeric forms underwent a slow polymerization. It was suggested that \"biosynthetic\" L-threonine dehydratase from E. coli K-12 is a set of multiple oligomeric forms, having different kinetic parameters. Probably, each form of the enzyme has a \"simple\" kinetics characterized by hyperbolic or sigmoidal shape of v versus [S]o plots. The rate of equilibrium installation between the oligomeric forms was small in comparison with the enzyme reaction velocity, that lead to the complex kinetic curves, appearing as a result of summing up of the kinetics inherent to theindividual forms.", "contents": "Studies of homogeneous \"biosynthetic\" L-threonine dehydratase from Escherichia coli K-12. Some kinetic properties and molecular multiplicity. \"Biosynthetic\" L-threonine dehydratase (EC 4.2.1.16) was purified to a homogeneous state with 29% yield of total activity from Escherichia coli K-12. The homogeneity of the enzyme was shown by polyacrylamide gel disc electrophoresis in the presence of dodecyl sulphate. The enzyme consisted of equal subunits having a molecular weight of about 57 000. The polyacrylamide gel disc electrophoresis has shown that the native enzyme consisted of a set of oligomeric forms. The multiplicity of molecular organization of the enzyme was reflected in complicated kinetic behaviour: at pH greater than 9 on the plots of initial reaction rate (v) versus initial substrate concentration ([S]o) there were four inflexion points (two intermediate plateaux), the position and deepness of which depended on enzyme concentration. At pH 8.3 on the v versus [S]o plots appeared two inflexion points (one intermediate plateu), the position of which practically did not depend on enzyme concentration in the reaction mixture, but strongly depended on the enzyme concentration in the stock solution. Repeated polyacrylamide gel disc electrophoresis of several oligomeric forms, isolated by the first electrophoresis, has shown that the oligomeric forms underwent a slow polymerization. It was suggested that \"biosynthetic\" L-threonine dehydratase from E. coli K-12 is a set of multiple oligomeric forms, having different kinetic parameters. Probably, each form of the enzyme has a \"simple\" kinetics characterized by hyperbolic or sigmoidal shape of v versus [S]o plots. The rate of equilibrium installation between the oligomeric forms was small in comparison with the enzyme reaction velocity, that lead to the complex kinetic curves, appearing as a result of summing up of the kinetics inherent to theindividual forms."}
{"id": "PMID:240429", "title": "Studies on aspartase. II. Role of sulfhydryl groups in aspartase from Escherichia coli.", "content": "Aspartase (L-aspartate ammonia-lyase, EC 4.3.1.1) of Escherichia coli W contains 38 half-cystine residues per tetrameric enzyme molecule. Two sulfhydryl groups were modified with N-ethylmaleimide or 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) per subunit, while 8.3 sulfhydryl groups were titrated with p-mercuribenzoic acid. In the presence of 4 M guanidine - HCl, 8.6 sulfhydryl groups reacted with DTNB per subunit. Aspartase was inactivated by various sulfhydryl reagents following pseudo-first-order kinetics. Upon modification of one sulfhydryl group per subunit with N-Ethylmaleimide, 85% of the original activity was lost; a complete inactivation was attained concomitant with the modification of two sulfhydryl groups. These results indicate that one or two sulfhydryl groups are essential for enzyme activity. L-Aspartate and DL-erythro-beta-hydroxyaspartate markedly protected the enzyme against N-ethylmaleimide-inactivation. Only the compounds having an amino group at the alpha-position exhibited protection, indicating that the amino group of the substrate contributes to the protection of sulfhydryl groups of the enzyme. Examination of enzymatic properties after N-ethylmaleimide modification revealed that 5-fold increase in the Km value for L-aspartate and a shift of the optimum pH for the activity towards acidic pH were brought about by the modification, while neither dissociation into subunits nor aggregation occurred. These results indicate that the influence of the sulfhydryl group modification is restricted to the active site or its vicinity of the enzyme.", "contents": "Studies on aspartase. II. Role of sulfhydryl groups in aspartase from Escherichia coli. Aspartase (L-aspartate ammonia-lyase, EC 4.3.1.1) of Escherichia coli W contains 38 half-cystine residues per tetrameric enzyme molecule. Two sulfhydryl groups were modified with N-ethylmaleimide or 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) per subunit, while 8.3 sulfhydryl groups were titrated with p-mercuribenzoic acid. In the presence of 4 M guanidine - HCl, 8.6 sulfhydryl groups reacted with DTNB per subunit. Aspartase was inactivated by various sulfhydryl reagents following pseudo-first-order kinetics. Upon modification of one sulfhydryl group per subunit with N-Ethylmaleimide, 85% of the original activity was lost; a complete inactivation was attained concomitant with the modification of two sulfhydryl groups. These results indicate that one or two sulfhydryl groups are essential for enzyme activity. L-Aspartate and DL-erythro-beta-hydroxyaspartate markedly protected the enzyme against N-ethylmaleimide-inactivation. Only the compounds having an amino group at the alpha-position exhibited protection, indicating that the amino group of the substrate contributes to the protection of sulfhydryl groups of the enzyme. Examination of enzymatic properties after N-ethylmaleimide modification revealed that 5-fold increase in the Km value for L-aspartate and a shift of the optimum pH for the activity towards acidic pH were brought about by the modification, while neither dissociation into subunits nor aggregation occurred. These results indicate that the influence of the sulfhydryl group modification is restricted to the active site or its vicinity of the enzyme."}
{"id": "PMID:240430", "title": "Circular dichroism studies of dihydrofolate reductase from a methotrexate-resistant strain of Escherichia coli B, MB 1428: ternary complexes.", "content": "Circular dichroism has been used to monitor the binding of pyridine nucleotide cofactors to enzyme-folate analog complexes of dihydrofolate reductase from Escherichia coli B (MB 1428). The enzyme binds one molar equivalent of many folate analogs and two molar equivalents of several pyridine nucleotide cofactors. The apo-enzyme has very low optical activity. The binding of folate analogs including folate, dihydrofolate, methotrexate, trimethoprim and pyrimethamine induce large Cotton effects. Pyridine nucleotides when bound to the enzyme-folate analog complexes also induce new optically active bands; all the effects being due to the first molar equivalent of cofactor bound. NADPH and NADP+ induce very similar bands when bound to the enzyme-methotrexate complex suggesting that the geometry of the complexes formed are very similar. The oxidized and reduced cofactor likewise have similar effects on the enzyme-folate complex. However, NADPH and NADP+ addition to both the enzyme-trimethoprim and enzyme-pyrimethamine complexes have significantly different effects on the circular dichroism spectra, suggesting that the inhibitors which are less homologous to the natural dihydrofolate substrate allow more conformational freedom in the enzyme-inhibitor-cofactor complex. In most cases the prior binding of the folate analog greatly increases the binding of the first molar equivalent of cofactor so that at concentrations of approx. 5-20 muM the binding appears stoichiometric. Pyrimethamine is an exception in that it apparently has no effect on the binding of NADPH to the enzyme.", "contents": "Circular dichroism studies of dihydrofolate reductase from a methotrexate-resistant strain of Escherichia coli B, MB 1428: ternary complexes. Circular dichroism has been used to monitor the binding of pyridine nucleotide cofactors to enzyme-folate analog complexes of dihydrofolate reductase from Escherichia coli B (MB 1428). The enzyme binds one molar equivalent of many folate analogs and two molar equivalents of several pyridine nucleotide cofactors. The apo-enzyme has very low optical activity. The binding of folate analogs including folate, dihydrofolate, methotrexate, trimethoprim and pyrimethamine induce large Cotton effects. Pyridine nucleotides when bound to the enzyme-folate analog complexes also induce new optically active bands; all the effects being due to the first molar equivalent of cofactor bound. NADPH and NADP+ induce very similar bands when bound to the enzyme-methotrexate complex suggesting that the geometry of the complexes formed are very similar. The oxidized and reduced cofactor likewise have similar effects on the enzyme-folate complex. However, NADPH and NADP+ addition to both the enzyme-trimethoprim and enzyme-pyrimethamine complexes have significantly different effects on the circular dichroism spectra, suggesting that the inhibitors which are less homologous to the natural dihydrofolate substrate allow more conformational freedom in the enzyme-inhibitor-cofactor complex. In most cases the prior binding of the folate analog greatly increases the binding of the first molar equivalent of cofactor so that at concentrations of approx. 5-20 muM the binding appears stoichiometric. Pyrimethamine is an exception in that it apparently has no effect on the binding of NADPH to the enzyme."}
{"id": "PMID:240431", "title": "Isolation of an N-acetyl-DL-phenylalanine beta-naphthyl esterase from rabbit peritoneal polymorphonuclear leukocytes.", "content": "An N-acetyl-DL-phenylalanine beta-naphthyl esterase has been purified 26-fold from rabbit peritoneal polymorphonuclear leukocytes. The purified enzyme was inhibited by 10(-7) M p-nitrophenylethyl-5-chloropentylphosphonate. The apparent Km for hydrolysis of N-acetyl-DL-phenylalanine beta-naphthyl ester is 71 muM. Optimal reaction rates were observed at pH 6-8. No divalent cation requirement for the activation of the enzyme activity was observed. The esterase activity was neither inhibited nor stimulated by bacterial factor, complement component C5a, guanosine 3',5'-monophosphate (cyclic GMP) and adenosine 3',5'-monophosphate (cyclic AMP) which are attractants or repellents for polymorphonuclear leukocytes. High chemotactic activity was observed in the partially purified fraction of the enzyme. The chemotactic activity, like the enzyme activity, was completely inhibited by 10(-7) M phosphonate.", "contents": "Isolation of an N-acetyl-DL-phenylalanine beta-naphthyl esterase from rabbit peritoneal polymorphonuclear leukocytes. An N-acetyl-DL-phenylalanine beta-naphthyl esterase has been purified 26-fold from rabbit peritoneal polymorphonuclear leukocytes. The purified enzyme was inhibited by 10(-7) M p-nitrophenylethyl-5-chloropentylphosphonate. The apparent Km for hydrolysis of N-acetyl-DL-phenylalanine beta-naphthyl ester is 71 muM. Optimal reaction rates were observed at pH 6-8. No divalent cation requirement for the activation of the enzyme activity was observed. The esterase activity was neither inhibited nor stimulated by bacterial factor, complement component C5a, guanosine 3',5'-monophosphate (cyclic GMP) and adenosine 3',5'-monophosphate (cyclic AMP) which are attractants or repellents for polymorphonuclear leukocytes. High chemotactic activity was observed in the partially purified fraction of the enzyme. The chemotactic activity, like the enzyme activity, was completely inhibited by 10(-7) M phosphonate."}
{"id": "PMID:240432", "title": "Metabolic responses of perfused rat livers to alpha- and beta-adrenergic agonists, glucagon and cyclic AMP.", "content": "1. The mechanism of action of glucagon and epinephrine was studied in perfused rat livers. Hormone-induced transitions from one metabolic steady state to another were followed in a non-recirculating perfusion system. Glucose and lactate production rates, oxygen uptake and K+ redistribution were measured. 2. Glucagon (3 nM), cyclic AMP (0.2 mM) and epinephrine (0.5 muM) had similar effects on K+ concentrations in the perfusate. Glycogenolysis responded more rapidly and O2 uptake was enhanced to a larger extent with epinephrine than with the other agents. alpha- and beta-receptor responses were differentiated by the use of phenylephrine (0.5 muM), isoproterenol (0.5 muM) and adrenergic blocking agents (phentolamine and beta-blocker Ro 3-4787 at 0.1 mM). 3. alpha-receptors mediated an activation of glucose production that was very rapid and was paralleled by a transient decrease of K+ concentrations in the effluent from the liver, lactate production rose gradually. Respiration was also enhanced, but fell again as lactate production increased. 4. beta-receptor stimulation was followed by an increase of glucose production that was less drastic and was paralleled by a K+ release, lactate production and respiration were only slightly enhanced. beta stimulation and glucagon both resulted in an inhibition of the alpha-adrenergic effect on lactate release and simultaneously increased O2 uptake. 5. We concluded that in perfused rat livers alpha- as well as beta-adrenergic receptor stimulation resulted in an activation of glycogenolysis, possibly by two different mechanisms.", "contents": "Metabolic responses of perfused rat livers to alpha- and beta-adrenergic agonists, glucagon and cyclic AMP. 1. The mechanism of action of glucagon and epinephrine was studied in perfused rat livers. Hormone-induced transitions from one metabolic steady state to another were followed in a non-recirculating perfusion system. Glucose and lactate production rates, oxygen uptake and K+ redistribution were measured. 2. Glucagon (3 nM), cyclic AMP (0.2 mM) and epinephrine (0.5 muM) had similar effects on K+ concentrations in the perfusate. Glycogenolysis responded more rapidly and O2 uptake was enhanced to a larger extent with epinephrine than with the other agents. alpha- and beta-receptor responses were differentiated by the use of phenylephrine (0.5 muM), isoproterenol (0.5 muM) and adrenergic blocking agents (phentolamine and beta-blocker Ro 3-4787 at 0.1 mM). 3. alpha-receptors mediated an activation of glucose production that was very rapid and was paralleled by a transient decrease of K+ concentrations in the effluent from the liver, lactate production rose gradually. Respiration was also enhanced, but fell again as lactate production increased. 4. beta-receptor stimulation was followed by an increase of glucose production that was less drastic and was paralleled by a K+ release, lactate production and respiration were only slightly enhanced. beta stimulation and glucagon both resulted in an inhibition of the alpha-adrenergic effect on lactate release and simultaneously increased O2 uptake. 5. We concluded that in perfused rat livers alpha- as well as beta-adrenergic receptor stimulation resulted in an activation of glycogenolysis, possibly by two different mechanisms."}
{"id": "PMID:240433", "title": "An NMR investigation of electron transfer in the copper-protein, plastocyanin.", "content": "1. The proton NMR spectra of oxidised and reduced French bean plastocyanin have been recorded on a 270 MHz pulsed spctrometer. 2. The spectrum of a mixture containing the protein in the paramagnetic Cu(II) and diamagnetic Cu(I) states is a superposition of the separate spectra. When ferrirate spectra. 3. The results show that self-exchange between Cu(II)- and Cu(I)-plastocyanin is slow on the NMR time scale (kex less than 2-10(4) M-1-s-1 at 50 degrees C), and that electron transfer in the presence of ferricyanide is rapid (k greater than 1-10(5) M-1-s-1).", "contents": "An NMR investigation of electron transfer in the copper-protein, plastocyanin. 1. The proton NMR spectra of oxidised and reduced French bean plastocyanin have been recorded on a 270 MHz pulsed spctrometer. 2. The spectrum of a mixture containing the protein in the paramagnetic Cu(II) and diamagnetic Cu(I) states is a superposition of the separate spectra. When ferrirate spectra. 3. The results show that self-exchange between Cu(II)- and Cu(I)-plastocyanin is slow on the NMR time scale (kex less than 2-10(4) M-1-s-1 at 50 degrees C), and that electron transfer in the presence of ferricyanide is rapid (k greater than 1-10(5) M-1-s-1)."}
{"id": "PMID:240435", "title": "Studies on the charge transfer band in high spin state of ferric myoglobin and hemoglobin by low temperature optical and magnetic circular dichroism spectroscopy.", "content": "The behavior of charge transfer band, appearing at 600-650 nm in ferric high spin derivatives of myoglobin and hemoglobin, was studied under various conditions by low temperature optical and magnetic circular dichroism spectroscopy. Optical absorption spectra have demonstrated that: (1) The charge transfer band at 630 nm of myoglobin (Fe3+)-H2O (pH 7.0) at room temperature split into three bands, 627 nm, 645 nm and 664 nm (shoulder) at 77 degrees K, whereas that of hemoglobin (Fe3+)-H2O showed no splitting. (2) By lowering the pH value from 7.5 to 4.3 this splitting in myoglobin was observed to disappear only in the presence of a small amount of phosphate ion, accompanying a midpoint at pH 6.7 +/- 0.1. This does not originate from the released hemin. (3) Hemin (pH 7.55) showed no splitting of the charge transfer band at 77 degrees K. (4) This splitting depended on the species of 6th ligand. For myoglobin-F- the splitting could scarcely be observed, whereas the proton-donating ligands such as HCOOH and CH3OH exhibit the splitting as well as H2O. Magnetic circular dichroism spectra have demonstrated that: (5) The charge transfer band at 600-500 nm indicated Faraday A term and B term. (6) A negative B term band was observed at 650 nm for myoglobin-H2O in the glassic solvent of potassium glycerophosphate-glycerol, whereas it was not observed for hemoglobin-H2O. Several discussions were performed on the origin of splitting of the charge transfer band in myoglobin-H2O. It is now concluded that the hydrogen bond between the 6th ligand and the distal histidine contributes to the splitting of the charge transfer band around 630 nm for myoglobin Fe3+)-H2O at low temperature and that disappearance of the splitting at low pH is originated from the presence of phosphate ion.", "contents": "Studies on the charge transfer band in high spin state of ferric myoglobin and hemoglobin by low temperature optical and magnetic circular dichroism spectroscopy. The behavior of charge transfer band, appearing at 600-650 nm in ferric high spin derivatives of myoglobin and hemoglobin, was studied under various conditions by low temperature optical and magnetic circular dichroism spectroscopy. Optical absorption spectra have demonstrated that: (1) The charge transfer band at 630 nm of myoglobin (Fe3+)-H2O (pH 7.0) at room temperature split into three bands, 627 nm, 645 nm and 664 nm (shoulder) at 77 degrees K, whereas that of hemoglobin (Fe3+)-H2O showed no splitting. (2) By lowering the pH value from 7.5 to 4.3 this splitting in myoglobin was observed to disappear only in the presence of a small amount of phosphate ion, accompanying a midpoint at pH 6.7 +/- 0.1. This does not originate from the released hemin. (3) Hemin (pH 7.55) showed no splitting of the charge transfer band at 77 degrees K. (4) This splitting depended on the species of 6th ligand. For myoglobin-F- the splitting could scarcely be observed, whereas the proton-donating ligands such as HCOOH and CH3OH exhibit the splitting as well as H2O. Magnetic circular dichroism spectra have demonstrated that: (5) The charge transfer band at 600-500 nm indicated Faraday A term and B term. (6) A negative B term band was observed at 650 nm for myoglobin-H2O in the glassic solvent of potassium glycerophosphate-glycerol, whereas it was not observed for hemoglobin-H2O. Several discussions were performed on the origin of splitting of the charge transfer band in myoglobin-H2O. It is now concluded that the hydrogen bond between the 6th ligand and the distal histidine contributes to the splitting of the charge transfer band around 630 nm for myoglobin Fe3+)-H2O at low temperature and that disappearance of the splitting at low pH is originated from the presence of phosphate ion."}
{"id": "PMID:240436", "title": "Magnetic susceptibility measurements of deoxygenated hemoglobins and isolated chains.", "content": "Static magnetic susceptibility measurements have been performed in a wide temperature range (4.5-300 degrees K) on ligquid/frozen solutions of deoxygenated human hemoglobin and its isolated chains. The effects of buffer, pH, dielectric constant and phosphate have been investigated. Measurements have been done also on human fetal chains, on des-Arg and SucNEt-des-Arg hemoglobins. In all the proteins under study of the Fe2+ is the high spin state (S=2). At room temperature the magnetic moments lie in range 4.90 (theoretical spin-only value) to 5.45 Bohr magnetons. Local differences between the iron sites are revealed by the low temperature measurements. A mechanism is proposed to explain the effect of phosphate binding on the magnetic susceptibility.", "contents": "Magnetic susceptibility measurements of deoxygenated hemoglobins and isolated chains. Static magnetic susceptibility measurements have been performed in a wide temperature range (4.5-300 degrees K) on ligquid/frozen solutions of deoxygenated human hemoglobin and its isolated chains. The effects of buffer, pH, dielectric constant and phosphate have been investigated. Measurements have been done also on human fetal chains, on des-Arg and SucNEt-des-Arg hemoglobins. In all the proteins under study of the Fe2+ is the high spin state (S=2). At room temperature the magnetic moments lie in range 4.90 (theoretical spin-only value) to 5.45 Bohr magnetons. Local differences between the iron sites are revealed by the low temperature measurements. A mechanism is proposed to explain the effect of phosphate binding on the magnetic susceptibility."}
{"id": "PMID:240438", "title": "Hydrogen ion titration of lysozyme in alcohol-water solutions.", "content": "H+ titration curves of hen egg-white lysozyme were obtained at 0.15 I in the presence of small amounts (less than 15%) of methanol, ethanol and n-propanol. The acidity constants of two groups (whose pK values in water are, respectively, 42 and 3.5) are increased in water-alcohol mixtures in comparison to water. From the evaluation of these constants as a function of alcohol concentration and hydrocarbon chain length, it is suggested that these alcohols interact specifically with lysozyme. As pK values of 4.2 and 3.5 in water are generally assigned to Asp-101 and Asp-52 respectively, it seems that interaction occurs within the active site of the enzyme.", "contents": "Hydrogen ion titration of lysozyme in alcohol-water solutions. H+ titration curves of hen egg-white lysozyme were obtained at 0.15 I in the presence of small amounts (less than 15%) of methanol, ethanol and n-propanol. The acidity constants of two groups (whose pK values in water are, respectively, 42 and 3.5) are increased in water-alcohol mixtures in comparison to water. From the evaluation of these constants as a function of alcohol concentration and hydrocarbon chain length, it is suggested that these alcohols interact specifically with lysozyme. As pK values of 4.2 and 3.5 in water are generally assigned to Asp-101 and Asp-52 respectively, it seems that interaction occurs within the active site of the enzyme."}
{"id": "PMID:240439", "title": "Some features of hydrogen (ion) secretion by the frog skin.", "content": "We have studied the movements of H+ from the in vitro frog skin into the outside solution because it has been suggested that the movement of sodium from the outside solution into the skin may result from the forced exchange of Na+ by H+. Our main observations can be summarized as follows: (a) Hydrogen moves from the skin into the outside solution at a rate of 0.04 muequiv-cm-2-h-1 while Na+ influx had a value of 0.49 muequiv-cm-2-h-1. (b) The rate of H+ secretion is not significantly affected by substituting the Na+ in the outside solution by K+ nor by inhibiting Na+ influx with amiloride (5-10(-5) M). (c) Acetazolamide (5-10(-3) M) blocked H+ secretion without altering the potential difference across the skin. (d) The rate of H+ production is not underestimated because it may have been neutralized by HCO3- secreted into the outside solution in exchange for Cl-. Substituting all the Cl- by SO4(2-) in the outside solutions does not result in an increase in the rate of H+ production. (e) The steady-state rate of H+ secretion is not affected by large changes in electrochemical potential gradients for H+. Neither abolishing the potential difference across the skin nor a 10-fold change in H+ concentration in the outside solution affected significantly the steady-state rate of H+ secretion. (f) The H+ secretion was abolished by the metabolic inhibitors dinitrophenol (1-10(-4) M) and Antimycin A (1.5-10(-6) M) which also markedly reduced the potential difference across the skin. Observations (a), (b), and (c) suggest that H+ and Na+ movements across the outer border of the isolated frog skin are not coupled. The ratio of Na+ to H+ movements is very different from unity and Na+ movements can be abolished without any effects on H+ secretion and conversely H+ movements can be abolished without interruption of Na+ uptake. A second conclusion suggested by these results is that the H+ secretion does not result from movement of H+ following its electrochemical potential gradient since that rate of secretion is not affected by marked changes in either potential or [H+]. Furthermore, the effects of metabolic inhibitors suggest that H+ secretion requires the expenditure of energy by the cell.", "contents": "Some features of hydrogen (ion) secretion by the frog skin. We have studied the movements of H+ from the in vitro frog skin into the outside solution because it has been suggested that the movement of sodium from the outside solution into the skin may result from the forced exchange of Na+ by H+. Our main observations can be summarized as follows: (a) Hydrogen moves from the skin into the outside solution at a rate of 0.04 muequiv-cm-2-h-1 while Na+ influx had a value of 0.49 muequiv-cm-2-h-1. (b) The rate of H+ secretion is not significantly affected by substituting the Na+ in the outside solution by K+ nor by inhibiting Na+ influx with amiloride (5-10(-5) M). (c) Acetazolamide (5-10(-3) M) blocked H+ secretion without altering the potential difference across the skin. (d) The rate of H+ production is not underestimated because it may have been neutralized by HCO3- secreted into the outside solution in exchange for Cl-. Substituting all the Cl- by SO4(2-) in the outside solutions does not result in an increase in the rate of H+ production. (e) The steady-state rate of H+ secretion is not affected by large changes in electrochemical potential gradients for H+. Neither abolishing the potential difference across the skin nor a 10-fold change in H+ concentration in the outside solution affected significantly the steady-state rate of H+ secretion. (f) The H+ secretion was abolished by the metabolic inhibitors dinitrophenol (1-10(-4) M) and Antimycin A (1.5-10(-6) M) which also markedly reduced the potential difference across the skin. Observations (a), (b), and (c) suggest that H+ and Na+ movements across the outer border of the isolated frog skin are not coupled. The ratio of Na+ to H+ movements is very different from unity and Na+ movements can be abolished without any effects on H+ secretion and conversely H+ movements can be abolished without interruption of Na+ uptake. A second conclusion suggested by these results is that the H+ secretion does not result from movement of H+ following its electrochemical potential gradient since that rate of secretion is not affected by marked changes in either potential or [H+]. Furthermore, the effects of metabolic inhibitors suggest that H+ secretion requires the expenditure of energy by the cell."}
{"id": "PMID:240440", "title": "Effect of changes in feeding schedule on the diurnal rhythms and daily activity levels of intestinal brush border enzymes and transport systems.", "content": "The activities of rat intestinal enzymes, sucrase, lactase, maltase, trehalase, gamma-glutamyltransferase, leucylnaphthylamide-hydrolyzing activity, and the transport system for glucose follow diurnal rhythms on ad libitum and restricted feeding regimes. In response to 6 days of restricted feeding, food available between 1400 and 1800 Eastern Standard Time, all rhythms shifted in time and the daily levels of activities were changed. Alkaline phosphatase activity followed a diurnal rhythm only in restricted fed animals. In restricted fed rats several activity patterns were observed, some with short periods of maximum activity, 3 h or less, and some with plateaus of maximum activity, 5-9 h long. In respect to the time of day of the synchronizer, sucrase peaked before feeding, glucose transport peaked during feeding, alkaline phosphatase peaked after feeding, and the other enzymes had higher levels of activity before, during and after feeding. The effect of restricted feeding on the daily activity levels were: a decrease in leucylnaphthylamide-hydrolyzing activity, no change in alkaline phosphatase, and increases in the others. These enzyme and transport systems exhibit a large amount of individual regulation or control as reflected by the lack of a uniform activity pattern and response to the synchronizer, and the variation in direction and magnitude of the adaptations to restricted feeding.", "contents": "Effect of changes in feeding schedule on the diurnal rhythms and daily activity levels of intestinal brush border enzymes and transport systems. The activities of rat intestinal enzymes, sucrase, lactase, maltase, trehalase, gamma-glutamyltransferase, leucylnaphthylamide-hydrolyzing activity, and the transport system for glucose follow diurnal rhythms on ad libitum and restricted feeding regimes. In response to 6 days of restricted feeding, food available between 1400 and 1800 Eastern Standard Time, all rhythms shifted in time and the daily levels of activities were changed. Alkaline phosphatase activity followed a diurnal rhythm only in restricted fed animals. In restricted fed rats several activity patterns were observed, some with short periods of maximum activity, 3 h or less, and some with plateaus of maximum activity, 5-9 h long. In respect to the time of day of the synchronizer, sucrase peaked before feeding, glucose transport peaked during feeding, alkaline phosphatase peaked after feeding, and the other enzymes had higher levels of activity before, during and after feeding. The effect of restricted feeding on the daily activity levels were: a decrease in leucylnaphthylamide-hydrolyzing activity, no change in alkaline phosphatase, and increases in the others. These enzyme and transport systems exhibit a large amount of individual regulation or control as reflected by the lack of a uniform activity pattern and response to the synchronizer, and the variation in direction and magnitude of the adaptations to restricted feeding."}
{"id": "PMID:240441", "title": "Requirement of galactolipids for photosystem I activity in lyophilized spinach chloroplasts.", "content": "1. The effect of monogalactosyl diacylglycerol and digalactosyl diacylglycerol on reconstitution of Photosystem I activity in heptane-extracted and galactolipase-treated spinach chloroplasts was investigated. 2. Both galactolipids, in a molar ratio with chlorophyll of 2.5, partially restored Photosystem I activity in heptane-extracted chloroplasts. An addition of saturating amounts of plastocyanin caused complete reactivation of Photosystem I. 3. Similarly, with galactolipase-treated chloroplasts, both galactolipids partially restored Phostosystem I activity and additional amounts of plastocyanin were required for complete reactivation. 4. The action of galactolipids on partial reconstitution of Photosystem I supports the suggestion of their structural role in the restoration of thylakoid membranes.", "contents": "Requirement of galactolipids for photosystem I activity in lyophilized spinach chloroplasts. 1. The effect of monogalactosyl diacylglycerol and digalactosyl diacylglycerol on reconstitution of Photosystem I activity in heptane-extracted and galactolipase-treated spinach chloroplasts was investigated. 2. Both galactolipids, in a molar ratio with chlorophyll of 2.5, partially restored Photosystem I activity in heptane-extracted chloroplasts. An addition of saturating amounts of plastocyanin caused complete reactivation of Photosystem I. 3. Similarly, with galactolipase-treated chloroplasts, both galactolipids partially restored Phostosystem I activity and additional amounts of plastocyanin were required for complete reactivation. 4. The action of galactolipids on partial reconstitution of Photosystem I supports the suggestion of their structural role in the restoration of thylakoid membranes."}
{"id": "PMID:240442", "title": "Vanadium compounds and ferrocyanide as ionic redox agents in photosynthesis.", "content": "The effect of such ionic redox agents as ferrocyanide and several vanadium compounds was determined on photosynthetic reactions of spinach chloroplasts. It was found that: 1. Vanadyl sulfate like ferrocyanide in moderately high concentrations (0.03 M) donates electrons to Photosystem II. 2. Decavanadate in the presence of 2,5-dibromothymoquinone accepts electrons in Photosystem II. 3. In the absence of a block between the two photosystems, decavanadate accepts electrons in Photosystem I in the vicinity of plastocyanin or beyond. 4. Vanadite and ferrocyanide in high concentrations (0.32 M) donate electrons to Photosystem I. 5. On the basis of chelator inhibition and polyoxyethylene sorbitan monolaureate treatment, the vanadite oxidation site is located near plastocyanin while the ferrocyanide site is between plastocyanin and P-700.", "contents": "Vanadium compounds and ferrocyanide as ionic redox agents in photosynthesis. The effect of such ionic redox agents as ferrocyanide and several vanadium compounds was determined on photosynthetic reactions of spinach chloroplasts. It was found that: 1. Vanadyl sulfate like ferrocyanide in moderately high concentrations (0.03 M) donates electrons to Photosystem II. 2. Decavanadate in the presence of 2,5-dibromothymoquinone accepts electrons in Photosystem II. 3. In the absence of a block between the two photosystems, decavanadate accepts electrons in Photosystem I in the vicinity of plastocyanin or beyond. 4. Vanadite and ferrocyanide in high concentrations (0.32 M) donate electrons to Photosystem I. 5. On the basis of chelator inhibition and polyoxyethylene sorbitan monolaureate treatment, the vanadite oxidation site is located near plastocyanin while the ferrocyanide site is between plastocyanin and P-700."}
{"id": "PMID:240443", "title": "Isolation and properties of Escherichia coli ATPase mutants with altered divalent metal specificity for ATP hydrolysis.", "content": "A method was devised for isolation of large numbers of energy-transducing ATPase (coupling factor) mutants based on a modification of the procedure of Hong and Ames (Hong, J. and Ames, B. N. (1971) Proc. Natl. Acad. Sci. U.S. 68, 3158-3162) for localized mutagenesis of any small region of the bacterial chromosome using transducing phages. The principle of this procedure is to mutate P1-transducing phage particles carrying the ATPase genes (Unc (uncoupled) DNA) using the strong chemical mutagen hydroxylamine. By transducing ilv- auxotrophs, a marker closely linked to Unc, to prototrophs, mutated Unc DNA can be introduced into the chromosome. We have used this method in conjunction with suitable selection procedures to isolate about 90 Unc- strains which have been classified by physiological, genetic, and biochemical criteria into three different phenotypes (Unc A, B, D). Mutants of the Unc D phenotype which were studied in detail were found to have the following properties: (1) aerobic growth yields on glucose are considerably lower than the wild type; growth occurs on glucose under anaerobic conditions; (2) Unc D lesions map near the ilv operon; (3) O2 uptake is comparable to the rate of wild type; (4) vesicles catalyze respiratory-dependent transhydrogenation, but show very low levels of Ca2+ ATP-dependent transhydrogenation; Mg2+ is ineffective; (5) oxidative phosphorylation is almost completely blocked irrespective of which metal ion is used; (6) the specific activity of ATPase is only about 20% of the wild type: (7) purified ATPase was found to have a marked specificity for Ca2+ as a divalent metal for ATP hydrolysis. A summary of properties of the new Unc mutants is discussed.", "contents": "Isolation and properties of Escherichia coli ATPase mutants with altered divalent metal specificity for ATP hydrolysis. A method was devised for isolation of large numbers of energy-transducing ATPase (coupling factor) mutants based on a modification of the procedure of Hong and Ames (Hong, J. and Ames, B. N. (1971) Proc. Natl. Acad. Sci. U.S. 68, 3158-3162) for localized mutagenesis of any small region of the bacterial chromosome using transducing phages. The principle of this procedure is to mutate P1-transducing phage particles carrying the ATPase genes (Unc (uncoupled) DNA) using the strong chemical mutagen hydroxylamine. By transducing ilv- auxotrophs, a marker closely linked to Unc, to prototrophs, mutated Unc DNA can be introduced into the chromosome. We have used this method in conjunction with suitable selection procedures to isolate about 90 Unc- strains which have been classified by physiological, genetic, and biochemical criteria into three different phenotypes (Unc A, B, D). Mutants of the Unc D phenotype which were studied in detail were found to have the following properties: (1) aerobic growth yields on glucose are considerably lower than the wild type; growth occurs on glucose under anaerobic conditions; (2) Unc D lesions map near the ilv operon; (3) O2 uptake is comparable to the rate of wild type; (4) vesicles catalyze respiratory-dependent transhydrogenation, but show very low levels of Ca2+ ATP-dependent transhydrogenation; Mg2+ is ineffective; (5) oxidative phosphorylation is almost completely blocked irrespective of which metal ion is used; (6) the specific activity of ATPase is only about 20% of the wild type: (7) purified ATPase was found to have a marked specificity for Ca2+ as a divalent metal for ATP hydrolysis. A summary of properties of the new Unc mutants is discussed."}
{"id": "PMID:240444", "title": "Electrical potential changes, H+ translocation and phosphorylation induced by short flash excitation in Rhodopseudomonas sphaeroides chromatophores.", "content": "1. The basal decay of the carotenoid shift of chromatophores from photosynthetic bacteria following short flash excitation is approximately biphasic. The decay indicates the dissipation of the transmembrane electrical potential. 2. The H+ efflux following rapid H+ binding after a flash, measured from the colour change of added cresol red, shows very similar kinetics to the carotenoid shift decay suggesting that the dissipation of the electric potential decay is a consequence of the H+ efflux. 3. The electric potential decay is stimulated when the chromatophore suspension is supplemented with ADP and Pi (in either the presence or absence of antimycin A). 4. The stimulated electric potential decay by ADP and Pi has a similar pH dependence to that of phosphorylation in continuous light. 5. The stimulation of the electric potential decay by ADP and Pi is reversed, by aurovertin, an antibiotic which inhibits phosphorylation. 6. The stimulation of the electric potential decay by ADP+Pi is also reversed by the inhibitors oligomycin and venturicidin. These inhibitors, but not aurovertin, also inhibit the fast phase of the decay under non-phosphorylating conditions. 7. Valinomycin accelerates the overall rate of decay of the electric potential, inhibits the ADP and Pi stimulated electric potential decay, and inhibits the flash-induced phosphorylation. The decay rate of the H+ efflux however, is slower in the presence of this ionophore. 8. Nigericin-type ionophores accelerate the overall decay rate of the H+ efflux and inhibit the ADP and Pi stimulated electric potential decay. The basal rate of the electric potential decay is unaffected by treatment with these ionophores. 9. When a coupling factor associated with the chromatophore ATPase is removed from the membrane, both the stimulation of the electric potential decay by ADP and Pi and ADP phosphorylation are inhibtied. Both reactions are completely restored after reconstitution with the crude coupling factor extract. The basal electric potential decay rate is not affected by the removal of coupling factor.", "contents": "Electrical potential changes, H+ translocation and phosphorylation induced by short flash excitation in Rhodopseudomonas sphaeroides chromatophores. 1. The basal decay of the carotenoid shift of chromatophores from photosynthetic bacteria following short flash excitation is approximately biphasic. The decay indicates the dissipation of the transmembrane electrical potential. 2. The H+ efflux following rapid H+ binding after a flash, measured from the colour change of added cresol red, shows very similar kinetics to the carotenoid shift decay suggesting that the dissipation of the electric potential decay is a consequence of the H+ efflux. 3. The electric potential decay is stimulated when the chromatophore suspension is supplemented with ADP and Pi (in either the presence or absence of antimycin A). 4. The stimulated electric potential decay by ADP and Pi has a similar pH dependence to that of phosphorylation in continuous light. 5. The stimulation of the electric potential decay by ADP and Pi is reversed, by aurovertin, an antibiotic which inhibits phosphorylation. 6. The stimulation of the electric potential decay by ADP+Pi is also reversed by the inhibitors oligomycin and venturicidin. These inhibitors, but not aurovertin, also inhibit the fast phase of the decay under non-phosphorylating conditions. 7. Valinomycin accelerates the overall rate of decay of the electric potential, inhibits the ADP and Pi stimulated electric potential decay, and inhibits the flash-induced phosphorylation. The decay rate of the H+ efflux however, is slower in the presence of this ionophore. 8. Nigericin-type ionophores accelerate the overall decay rate of the H+ efflux and inhibit the ADP and Pi stimulated electric potential decay. The basal rate of the electric potential decay is unaffected by treatment with these ionophores. 9. When a coupling factor associated with the chromatophore ATPase is removed from the membrane, both the stimulation of the electric potential decay by ADP and Pi and ADP phosphorylation are inhibtied. Both reactions are completely restored after reconstitution with the crude coupling factor extract. The basal electric potential decay rate is not affected by the removal of coupling factor."}
{"id": "PMID:240445", "title": "The extent of the stimulated electrical potential decay under phosphorylating conditions and the H+/ATP ratio in Rhodopseudomonas sphaeroides chromatophores following short flash excitation.", "content": "1. In chromatophores from Rps. sphaeroides, the stimulation by ADP and Pi of the electric potential decay indicated by the carotenoid shift is greater than the stimulation of the decay of pH change indicated by the colour change of added cresol red under similar conditions. This difference is attributed to H+ consumption during the synthesis of ATP. The ratio of H+ translocated across the membrane to ATP synthesized was estimated to be approximately 1.7 H+/ATP. 2. The stimulation of the electrical potential decay by ADP and Pi was found to be a constant fraction (10%) of the total decay when the flash intensity was varied. No 'critical' or 'threshold' potential was observed. 3. The stimulated electrical potential decay after a second flash, given within a few seconds of the first, was related to the amplitude of the electrical potential produced by the second flash (10%) but neither to the dark time between the flashes, nor to the total extent of the electrical potential above the dark level. These results are consistent with two hypotheses (a) the chromatophores are a mixed population of vesicles, only a small fraction (10%) of which possess an active ATP  synthesizing system (b) the activity of the ATP synthesizing system, though driven by a proton motive force, is controlled by electron transport processess. If alternative (a) is correct then the overall single turnover flash yield of 1 ATP per 1470 bacteriochlorophyll measured in (1) would mean that the yield of the active vesicles is approximately 10 ATP per 1470 bacteriochlorophyll or 30 ATP per vesicle. 4. The stimulation of the electrical potential decay by ADP and Pi is approximately 40% less in antimycin-treated chromatophores. It is shown that this is probably a consequence of antimycin-inhibited H+-release on the inside of the chromatophore vesicles following a flash.", "contents": "The extent of the stimulated electrical potential decay under phosphorylating conditions and the H+/ATP ratio in Rhodopseudomonas sphaeroides chromatophores following short flash excitation. 1. In chromatophores from Rps. sphaeroides, the stimulation by ADP and Pi of the electric potential decay indicated by the carotenoid shift is greater than the stimulation of the decay of pH change indicated by the colour change of added cresol red under similar conditions. This difference is attributed to H+ consumption during the synthesis of ATP. The ratio of H+ translocated across the membrane to ATP synthesized was estimated to be approximately 1.7 H+/ATP. 2. The stimulation of the electrical potential decay by ADP and Pi was found to be a constant fraction (10%) of the total decay when the flash intensity was varied. No 'critical' or 'threshold' potential was observed. 3. The stimulated electrical potential decay after a second flash, given within a few seconds of the first, was related to the amplitude of the electrical potential produced by the second flash (10%) but neither to the dark time between the flashes, nor to the total extent of the electrical potential above the dark level. These results are consistent with two hypotheses (a) the chromatophores are a mixed population of vesicles, only a small fraction (10%) of which possess an active ATP  synthesizing system (b) the activity of the ATP synthesizing system, though driven by a proton motive force, is controlled by electron transport processess. If alternative (a) is correct then the overall single turnover flash yield of 1 ATP per 1470 bacteriochlorophyll measured in (1) would mean that the yield of the active vesicles is approximately 10 ATP per 1470 bacteriochlorophyll or 30 ATP per vesicle. 4. The stimulation of the electrical potential decay by ADP and Pi is approximately 40% less in antimycin-treated chromatophores. It is shown that this is probably a consequence of antimycin-inhibited H+-release on the inside of the chromatophore vesicles following a flash."}
{"id": "PMID:240447", "title": "Systemic and pulmonary hemodynamic responses to adrenergic and cholinergic agonists during fetal development.", "content": "Systemic and pulmonary hemodynamic responses to adrenergic and cholinergic agonists were investigated in fetal lambs between 60 days and term gestation. The cardiovascular response to these agents increases with fetal age, and the increase is related to maturation of the effector system rather than the vascular receptors. The fetal pulmonary vascular bed and the ductus arteriosus are the primary components responding to acetylcholine; the systemic response is secondary to the occuring in the lung. Both fetal systemic and pulmonary vascular beds are under alpha-adrenergic control whereas the fetal heart is under beta-adrenergic control.", "contents": "Systemic and pulmonary hemodynamic responses to adrenergic and cholinergic agonists during fetal development. Systemic and pulmonary hemodynamic responses to adrenergic and cholinergic agonists were investigated in fetal lambs between 60 days and term gestation. The cardiovascular response to these agents increases with fetal age, and the increase is related to maturation of the effector system rather than the vascular receptors. The fetal pulmonary vascular bed and the ductus arteriosus are the primary components responding to acetylcholine; the systemic response is secondary to the occuring in the lung. Both fetal systemic and pulmonary vascular beds are under alpha-adrenergic control whereas the fetal heart is under beta-adrenergic control."}
{"id": "PMID:240448", "title": "Cortisol treatment of neonatal rats: effects on enzymes in kidney, liver and heart.", "content": "Cortisol treatment of neonatal rats did not have permanent effects on the levels of 2-7 enzymes in heart, kidney, brain, and liver, even though some exhibited abnormally high concentrations during the first 1 or 2 weeks. An injection of cortisol at birth evoked premature rises of glucose-6-phosphatase (G6P-ase) in kidney, of soluble and particulate aspartate aminotransferase (AAT) in kidney and heart and of soluble AAT in liver. These enzymes (with the exception of soluble AAT in the female) did not respond to cortisol in adult rats. The significance of the varying effects of cortisol is discussed in relation to previously studied developmental enzyme formations.", "contents": "Cortisol treatment of neonatal rats: effects on enzymes in kidney, liver and heart. Cortisol treatment of neonatal rats did not have permanent effects on the levels of 2-7 enzymes in heart, kidney, brain, and liver, even though some exhibited abnormally high concentrations during the first 1 or 2 weeks. An injection of cortisol at birth evoked premature rises of glucose-6-phosphatase (G6P-ase) in kidney, of soluble and particulate aspartate aminotransferase (AAT) in kidney and heart and of soluble AAT in liver. These enzymes (with the exception of soluble AAT in the female) did not respond to cortisol in adult rats. The significance of the varying effects of cortisol is discussed in relation to previously studied developmental enzyme formations."}
{"id": "PMID:240449", "title": "Pharmacotherapy in early infantile autism.", "content": "An up-to-date review of drug treatment in psychoses of early childhood is presented. At the present time, of all biological interventions in these developmental disorders, drug treatment alone remains a valuable addition or an essential treatment modality of the total treatment. Experience has shown that a therapeutically effective potent drug can make the autistic child more amenable to other therapies, including special education. However, knowledge is lacking about the effect of various psychoactive agents on cognition in this patient population as well as their influence on growth, weight, endocrine systems, and organs. Drugs currently in use treat symptoms, not diseases. A great need for classification in this area persists. The same symptoms may be caused by a variety of etiologic factors, and autism may or may not be the earliest expression of childhood schizophrenia. It is suggested that clinical distinctions be correlated or even improved by certain biochemical, neuroendocrine, and physiological criteria; this also may be of considerable value in predicting whether a child can benefit from a specific drug.", "contents": "Pharmacotherapy in early infantile autism. An up-to-date review of drug treatment in psychoses of early childhood is presented. At the present time, of all biological interventions in these developmental disorders, drug treatment alone remains a valuable addition or an essential treatment modality of the total treatment. Experience has shown that a therapeutically effective potent drug can make the autistic child more amenable to other therapies, including special education. However, knowledge is lacking about the effect of various psychoactive agents on cognition in this patient population as well as their influence on growth, weight, endocrine systems, and organs. Drugs currently in use treat symptoms, not diseases. A great need for classification in this area persists. The same symptoms may be caused by a variety of etiologic factors, and autism may or may not be the earliest expression of childhood schizophrenia. It is suggested that clinical distinctions be correlated or even improved by certain biochemical, neuroendocrine, and physiological criteria; this also may be of considerable value in predicting whether a child can benefit from a specific drug."}
{"id": "PMID:240452", "title": "Biochemical, morphological and hybrid studies in hyperprolinemic mice.", "content": "Hyperprolinemia, hyperprolinuria and hydroxyprolinuria were observed in PRO/Re mice. Hepatic proline oxidase activity in PRO/Re mice was markedly deficient. It was demonstrated that the deficiency of proline oxidase activity was not due to the presence of an inhibitor. The mutant enzyme in PRO/Re showed no difference in heat stability but had a poor affinity for the substrate, L-proline as compared to normal enzymes. There was no significant proteinuria or hematuria in PRO/Re mice. Their serum protein and blood urea nitrogen were normal. Morphologic studies by light and electron microscopy demonstrated no abnormality in the renal tissues of PRO/Re up to 6 months of age, suggesting that hyperprolinemia did not cause renal damage. Pedigree studies showed that F1 generation (PRO/Re x CD 1) had approximately 50 percent of normal proline oxidase activity and significantly higher plasma proline. The distribution of hepatic proline oxidase activity in F2 GENERATION (F1 x F1) was characteristic of an autosomal recessive trait.", "contents": "Biochemical, morphological and hybrid studies in hyperprolinemic mice. Hyperprolinemia, hyperprolinuria and hydroxyprolinuria were observed in PRO/Re mice. Hepatic proline oxidase activity in PRO/Re mice was markedly deficient. It was demonstrated that the deficiency of proline oxidase activity was not due to the presence of an inhibitor. The mutant enzyme in PRO/Re showed no difference in heat stability but had a poor affinity for the substrate, L-proline as compared to normal enzymes. There was no significant proteinuria or hematuria in PRO/Re mice. Their serum protein and blood urea nitrogen were normal. Morphologic studies by light and electron microscopy demonstrated no abnormality in the renal tissues of PRO/Re up to 6 months of age, suggesting that hyperprolinemia did not cause renal damage. Pedigree studies showed that F1 generation (PRO/Re x CD 1) had approximately 50 percent of normal proline oxidase activity and significantly higher plasma proline. The distribution of hepatic proline oxidase activity in F2 GENERATION (F1 x F1) was characteristic of an autosomal recessive trait."}
{"id": "PMID:240454", "title": "Fluorescence and stopped-flow studies on the N in equilibrium F transition of serumalbumin.", "content": "In order to characterize the isomerization of serumalbumin in the acidic pH-range equilibrium and kinetic measurements of the intrinsic fluorescence of bovine serumalbumin and human serumalbumin were performed. Additional experiments with modified bovine serumalbumin made use of substituted 1.9 benzoxanthene dyes as SH-specific extrinsic fluorophores. The intrinsic fluorescence (lambda exc = 275 nm) shows a pH-dependent shift of the maximum of fluorescence emissions which correlates with the N in equilibrium F isomerization. This and the acid expansion at pH less than 3.5 is indicated by the pH-dependence of the fluorescence intensity at 350 nm. While tyrosine fluorescence is increased in all steps of the transition, tryptophane fluorescence is decreased in a different way for BSA (2 trp/molecule) and HSA (1 trp/molecule), the latter showing the N in equilibrium F transition only. Combining the tryptophan fluorescence data with the results from the SH-specific modification of BSA the conclusion may be drawn that the tryptophan residues in BSA and the SH-group belong to different domains of the molecule. Stopped-flow experiments prove the N in equilibrium F' and the F' in equilibrium F transitions to be separable along the time axis, the relaxation times being in the range between 40-50 and 300-600 msec respectively. For the \"expansion\" the kinetic constants critically depend on the initial pH conditions of the solutions. The backward reaction F leads to N seems to be a multistep isomerization process which is characterized by relaxation times greater than 1 sec.", "contents": "Fluorescence and stopped-flow studies on the N in equilibrium F transition of serumalbumin. In order to characterize the isomerization of serumalbumin in the acidic pH-range equilibrium and kinetic measurements of the intrinsic fluorescence of bovine serumalbumin and human serumalbumin were performed. Additional experiments with modified bovine serumalbumin made use of substituted 1.9 benzoxanthene dyes as SH-specific extrinsic fluorophores. The intrinsic fluorescence (lambda exc = 275 nm) shows a pH-dependent shift of the maximum of fluorescence emissions which correlates with the N in equilibrium F isomerization. This and the acid expansion at pH less than 3.5 is indicated by the pH-dependence of the fluorescence intensity at 350 nm. While tyrosine fluorescence is increased in all steps of the transition, tryptophane fluorescence is decreased in a different way for BSA (2 trp/molecule) and HSA (1 trp/molecule), the latter showing the N in equilibrium F transition only. Combining the tryptophan fluorescence data with the results from the SH-specific modification of BSA the conclusion may be drawn that the tryptophan residues in BSA and the SH-group belong to different domains of the molecule. Stopped-flow experiments prove the N in equilibrium F' and the F' in equilibrium F transitions to be separable along the time axis, the relaxation times being in the range between 40-50 and 300-600 msec respectively. For the \"expansion\" the kinetic constants critically depend on the initial pH conditions of the solutions. The backward reaction F leads to N seems to be a multistep isomerization process which is characterized by relaxation times greater than 1 sec."}
{"id": "PMID:240470", "title": "[Correlation of splenomegaly and blood picture changes in graft vs host reaction of the mouse].", "content": "The early phase of graft-versus-host-reaction is characterized by a rapid decline of lymphocytes in the peripheral blood, with a minimum between days 9 and 11, and return to normal until day 20 after spleen cell grafting. Erythrocytes and hematocrit do not change during this period. There is no causal correlation between splenomegaly and lymphopenia. Lymphopenia provides a criterium for experimental graft-versusu-host-reaction equivalent to the spleen-index.", "contents": "[Correlation of splenomegaly and blood picture changes in graft vs host reaction of the mouse]. The early phase of graft-versus-host-reaction is characterized by a rapid decline of lymphocytes in the peripheral blood, with a minimum between days 9 and 11, and return to normal until day 20 after spleen cell grafting. Erythrocytes and hematocrit do not change during this period. There is no causal correlation between splenomegaly and lymphopenia. Lymphopenia provides a criterium for experimental graft-versusu-host-reaction equivalent to the spleen-index."}
{"id": "PMID:240472", "title": "The effects of tetraphenylboron on spontaneous transmitter release at the frog neuromuscular junction.", "content": "1 The effects of tetraphenylboron (TPB) on spontaneous transmitter release were studied in the frog sartorius muscle preparation. 2 TPB (0.001-1 mM) produced a time-dependent increase in miniature endplate potential (m.e.p.p.) activity that was not sustained. TPB (0.1 mM) produced similar effects on m.e.p.p. frequency in normal Ringer solutions, in the absence of Ca2+ or Cl- and in the presence of excess Ca2+ and of tetrodotoxin. The effect of TPB (0.01 mM) was reduced but not abolished in the absence of Ca2+. 3 As m.e.p.p. frequency fell from its peak level in TPB (0.04 mM) m.e.p.p. amplitude was reduced. The reduction of m.e.p.p. amplitude was not prevented by choline (30-300 muM). 4 When m.e.p.p. activity fell below the noise level in the presence of TPB (0.1 mM), lanthanum (0.5 mM) was ineffective in promoting measurable m.e.p.p. activity. 5 The effects of TPB were slowly reversible by washing. 6 The results indicate that TPB acts to reduce the nerve terminal stores of acetylcholine, probably by a combination of rapid release and concomitant inhibition of transmitter storage.", "contents": "The effects of tetraphenylboron on spontaneous transmitter release at the frog neuromuscular junction. 1 The effects of tetraphenylboron (TPB) on spontaneous transmitter release were studied in the frog sartorius muscle preparation. 2 TPB (0.001-1 mM) produced a time-dependent increase in miniature endplate potential (m.e.p.p.) activity that was not sustained. TPB (0.1 mM) produced similar effects on m.e.p.p. frequency in normal Ringer solutions, in the absence of Ca2+ or Cl- and in the presence of excess Ca2+ and of tetrodotoxin. The effect of TPB (0.01 mM) was reduced but not abolished in the absence of Ca2+. 3 As m.e.p.p. frequency fell from its peak level in TPB (0.04 mM) m.e.p.p. amplitude was reduced. The reduction of m.e.p.p. amplitude was not prevented by choline (30-300 muM). 4 When m.e.p.p. activity fell below the noise level in the presence of TPB (0.1 mM), lanthanum (0.5 mM) was ineffective in promoting measurable m.e.p.p. activity. 5 The effects of TPB were slowly reversible by washing. 6 The results indicate that TPB acts to reduce the nerve terminal stores of acetylcholine, probably by a combination of rapid release and concomitant inhibition of transmitter storage."}
{"id": "PMID:240473", "title": "Renal tubular transport of paracetamol and its conjugates in the dog.", "content": "1 The renal tubular transport of paracetamol and its conjugates was investigated with renal clearance and stop flow studies in the dog. Paracetamol is sparingly bound to plasma proteins and therefore undergoes glomerular filtration. It is reabosrbed in the renal tubules by simple diffusion. 2 The conjugates of paracetamol, the sulphate and the glucuronide, both undergo glomerular filtration being weakly protein bound. At low concentrations in plasma both compounds are secreted by an active transport process. At higher concentrations both compounds are reabsorbed. Clearances are not dependent on urinary pH or flow rate. It is concluded that reabsorption is not a passive process but that there is an active bidirectional transport of the conjugates. 3 Net tubular secretion of the sulphate, but not the glucuronide, conjugate was inhibited by the administration of probenecid.", "contents": "Renal tubular transport of paracetamol and its conjugates in the dog. 1 The renal tubular transport of paracetamol and its conjugates was investigated with renal clearance and stop flow studies in the dog. Paracetamol is sparingly bound to plasma proteins and therefore undergoes glomerular filtration. It is reabosrbed in the renal tubules by simple diffusion. 2 The conjugates of paracetamol, the sulphate and the glucuronide, both undergo glomerular filtration being weakly protein bound. At low concentrations in plasma both compounds are secreted by an active transport process. At higher concentrations both compounds are reabsorbed. Clearances are not dependent on urinary pH or flow rate. It is concluded that reabsorption is not a passive process but that there is an active bidirectional transport of the conjugates. 3 Net tubular secretion of the sulphate, but not the glucuronide, conjugate was inhibited by the administration of probenecid."}
{"id": "PMID:240474", "title": "A quantitative microiontophoretic analysis of the responses of central neurones to noradrenaline: interactions with cobalt, manganese, verapamil and dichloroisoprenaline.", "content": "1. A new experimental procedure has been devised for the study of pharmacological antagonism in the central nervous sytem using automated microiontophoresis to deliver pulses of agonists and computer-generated histograms to quantify the neuronal response. The system allows study of potential antagonists having direct depressant effects and also of neurones with irregular or slow discharge rates. 2. The histogram analysis reveals the necessity for regular, periodic delivery of agonists during the assessment of agonist-antagonist interactions. Without regular repetitive delivery, many agonists, such as noradrenaline, exhibit an apparent but artifactual decrease in inhibitory potency after an interruption of agonist pulses. Examples of this phenomenon are shown, using cerebellar Punkinje cells and cerebral cortical neurones in rats anaesthetized with halothane. 3. Preliminary results with these computer-generated drug response histograms revealed manganese, cobalt, and verapamil to be generally ineffective as antagonists of noradrenaline, despite their direct depressant effects. 4. Conversely, dichloroisoprenaline (DCI), a beta-adrenoceptor antagonist, was effective in blocking noradrenaline-induced depressions of firing in the cerebral cortex at doses which caused over 50% decrease in spontaneous discharge.", "contents": "A quantitative microiontophoretic analysis of the responses of central neurones to noradrenaline: interactions with cobalt, manganese, verapamil and dichloroisoprenaline. 1. A new experimental procedure has been devised for the study of pharmacological antagonism in the central nervous sytem using automated microiontophoresis to deliver pulses of agonists and computer-generated histograms to quantify the neuronal response. The system allows study of potential antagonists having direct depressant effects and also of neurones with irregular or slow discharge rates. 2. The histogram analysis reveals the necessity for regular, periodic delivery of agonists during the assessment of agonist-antagonist interactions. Without regular repetitive delivery, many agonists, such as noradrenaline, exhibit an apparent but artifactual decrease in inhibitory potency after an interruption of agonist pulses. Examples of this phenomenon are shown, using cerebellar Punkinje cells and cerebral cortical neurones in rats anaesthetized with halothane. 3. Preliminary results with these computer-generated drug response histograms revealed manganese, cobalt, and verapamil to be generally ineffective as antagonists of noradrenaline, despite their direct depressant effects. 4. Conversely, dichloroisoprenaline (DCI), a beta-adrenoceptor antagonist, was effective in blocking noradrenaline-induced depressions of firing in the cerebral cortex at doses which caused over 50% decrease in spontaneous discharge."}
{"id": "PMID:240475", "title": "Effects of narcotic analgesic drugs on the cyclic adenosine 3',5'-monophosphate-adenylate cyclase system in rat brain.", "content": "1. The concentrations of cyclic adenosine 3',5'-monophosphate (cyclic AMP), measured in discrete brain areas removed from rats killed by microwave irradiation, rose transiently in most areas after the administration of morphine. The most pronounced changes, however, were found 2 h after doses of either 10 or 60 mg/kg morphine when cyclic AMP levels declined significantly in the hypothalamus, medulla and cerebellum. In morphine-tolerant rat brains there were no decreases in cyclic AMP levels. 2. Basal adenylate cyclase activity in crude nerve-ending fractions from discrete areas of rat brain was unaffected by the addition of active analgesic agonists, antagonists or inactive isomers to the assay medium in vitro, except for a nonspecific inhibition at drug concentrations of 1 mM. 3. The acute administration of morphine or levorphanol, but not dextrorphan produced transient increases in basal cyclase activity of crude nerve-ending preparations from midbrain and striatum. In morphine-tolerant rats, these changes in basal adenylate cyclase activity were no longer seen.", "contents": "Effects of narcotic analgesic drugs on the cyclic adenosine 3',5'-monophosphate-adenylate cyclase system in rat brain. 1. The concentrations of cyclic adenosine 3',5'-monophosphate (cyclic AMP), measured in discrete brain areas removed from rats killed by microwave irradiation, rose transiently in most areas after the administration of morphine. The most pronounced changes, however, were found 2 h after doses of either 10 or 60 mg/kg morphine when cyclic AMP levels declined significantly in the hypothalamus, medulla and cerebellum. In morphine-tolerant rat brains there were no decreases in cyclic AMP levels. 2. Basal adenylate cyclase activity in crude nerve-ending fractions from discrete areas of rat brain was unaffected by the addition of active analgesic agonists, antagonists or inactive isomers to the assay medium in vitro, except for a nonspecific inhibition at drug concentrations of 1 mM. 3. The acute administration of morphine or levorphanol, but not dextrorphan produced transient increases in basal cyclase activity of crude nerve-ending preparations from midbrain and striatum. In morphine-tolerant rats, these changes in basal adenylate cyclase activity were no longer seen."}
{"id": "PMID:240476", "title": "Displacement by metiamide of the dose-response curves to pentagastrin and methacholine in the conscious rat.", "content": "1. The effect of a specific histamine H2-receptor antagonist, metiamide, on the acid dose-response curves for pentagastrin or methacholine was studied in rats provided with Heidenhain pouches. 2. Metiamide induced a shift to the right of the dose-response curve to pentagastrin and lowered the maximal secretion. 3. In contrast, metiamide only increased the ED50 for methacholine but did not alter the calculated maximal response. 4. The effect of metiamide on pentagastrin and methacholine-induced secretion is in agreement with the previously suggested difference in the part played by mucosal histamine in the mode of action of the two stimulatory agents.", "contents": "Displacement by metiamide of the dose-response curves to pentagastrin and methacholine in the conscious rat. 1. The effect of a specific histamine H2-receptor antagonist, metiamide, on the acid dose-response curves for pentagastrin or methacholine was studied in rats provided with Heidenhain pouches. 2. Metiamide induced a shift to the right of the dose-response curve to pentagastrin and lowered the maximal secretion. 3. In contrast, metiamide only increased the ED50 for methacholine but did not alter the calculated maximal response. 4. The effect of metiamide on pentagastrin and methacholine-induced secretion is in agreement with the previously suggested difference in the part played by mucosal histamine in the mode of action of the two stimulatory agents."}
{"id": "PMID:240477", "title": "The effect of heparin and of acid-citrate-dextrose solution on screen filtration pressure of blood in experimental hypotension.", "content": "Anticoagulation with heparin may not always adequately protect an ischaemic vascular bed. A screen filtration device has been employed to study the in vitro actions of acid-citrate-dextrose (ACD) and heparin on blood from the dog in haemorrhagic shock. With both anticoagulants, blood obtained during shock caused greater filter obstruction than blood taken before shock. However, the increased obstruction was nearly four times greater with heparinized blood than with acid-citrate-dextrose blood. These findings suggest that the anticoagulant action of heparin may be markedly diminished in low blood flow states.", "contents": "The effect of heparin and of acid-citrate-dextrose solution on screen filtration pressure of blood in experimental hypotension. Anticoagulation with heparin may not always adequately protect an ischaemic vascular bed. A screen filtration device has been employed to study the in vitro actions of acid-citrate-dextrose (ACD) and heparin on blood from the dog in haemorrhagic shock. With both anticoagulants, blood obtained during shock caused greater filter obstruction than blood taken before shock. However, the increased obstruction was nearly four times greater with heparinized blood than with acid-citrate-dextrose blood. These findings suggest that the anticoagulant action of heparin may be markedly diminished in low blood flow states."}
{"id": "PMID:240479", "title": "Reassessment of failed beta-blocker treatment in angina pectoris by peak-exercise heart rate measurements.", "content": "Twenty-one patients with angina pectoris were treated with adrenergic beta-receptor antagonists. Previously the resting heart rate had been used as a guide to treatment, a reduction in the rate to 55-60 beats/min without symptomatic improvement indicating failure of medical treatment. These patients were re-evaluated before coronary arteriography using the peak-exercise heart rate as an index of adrenergic beta-receptor antagonism. The dose of beta-blocking drugs was increased to produce a peak-exercise heart rate of less than 100 beats/min or a consistent rate of 100-125 beats/min which would not lessen in spite of progressive dose increments. The resting heart rate was ignored. On these criteria 15 patients previously considered to have responded inadequately to beta-blockade responded satisfactorily and were therefore removed from the waiting list for coronary arteriography. They all remained well up to two years later. Six patients failed to respond and had coronary arteriography with a view to surgical treatment. Reliance on the resting heart rate as the index of optimum adrenergic beta-receptor antagonism is likely to lead to premature or unnecessary referral for surgery; the failure of beta-blockade in the treatment of angina pectoris can be determined simply and accurately by using peak-exercise heart rate.", "contents": "Reassessment of failed beta-blocker treatment in angina pectoris by peak-exercise heart rate measurements. Twenty-one patients with angina pectoris were treated with adrenergic beta-receptor antagonists. Previously the resting heart rate had been used as a guide to treatment, a reduction in the rate to 55-60 beats/min without symptomatic improvement indicating failure of medical treatment. These patients were re-evaluated before coronary arteriography using the peak-exercise heart rate as an index of adrenergic beta-receptor antagonism. The dose of beta-blocking drugs was increased to produce a peak-exercise heart rate of less than 100 beats/min or a consistent rate of 100-125 beats/min which would not lessen in spite of progressive dose increments. The resting heart rate was ignored. On these criteria 15 patients previously considered to have responded inadequately to beta-blockade responded satisfactorily and were therefore removed from the waiting list for coronary arteriography. They all remained well up to two years later. Six patients failed to respond and had coronary arteriography with a view to surgical treatment. Reliance on the resting heart rate as the index of optimum adrenergic beta-receptor antagonism is likely to lead to premature or unnecessary referral for surgery; the failure of beta-blockade in the treatment of angina pectoris can be determined simply and accurately by using peak-exercise heart rate."}
{"id": "PMID:240480", "title": "Criteria of fitness for anaesthesia in patients with chronic obstructive lung disease.", "content": "Twelve patients with severe chronic obstructive lung disease undergoing 15 operations were assessed with preoperative lung function tests and blood gas estimations. Their operative and postoperative course was followed. There were no deaths or serious complications. Patients fell into three groups: those with low respiratory capacity but normal blood gases, who required no special respiratory treatment apart from physiotherapy and antibiotics; those with hypoxaemia but normal arterial carbon dioxide pressure, who needed more prolonged oxygen treatment after operation; and those with hypoxaemia and hypercapnia, who needed postoperative ventilatory support. While forced expiratory volume in one second (FEV) is a good screening test in preoperative assessment it should be supplemented by arterial blood gas estimations in patients with an FEV of less than 1 litre.", "contents": "Criteria of fitness for anaesthesia in patients with chronic obstructive lung disease. Twelve patients with severe chronic obstructive lung disease undergoing 15 operations were assessed with preoperative lung function tests and blood gas estimations. Their operative and postoperative course was followed. There were no deaths or serious complications. Patients fell into three groups: those with low respiratory capacity but normal blood gases, who required no special respiratory treatment apart from physiotherapy and antibiotics; those with hypoxaemia but normal arterial carbon dioxide pressure, who needed more prolonged oxygen treatment after operation; and those with hypoxaemia and hypercapnia, who needed postoperative ventilatory support. While forced expiratory volume in one second (FEV) is a good screening test in preoperative assessment it should be supplemented by arterial blood gas estimations in patients with an FEV of less than 1 litre."}
{"id": "PMID:240481", "title": "Improvement in prognosis of myocardial infarction by long-term beta-adrenoreceptor blockade using practolol. A multicentre international study.", "content": "In a large-scale double-blind controlled trial of practolol (200 mg twice daily) in the long-term prophylactic treatment of 3038 patients recovering from acute myocardial infarction treatment was started one to four weeks after the acute attack. The trial was originally planned to include 4000 patients treated for at least a year but had to be terminated prematurely because of the serious oculocutaneous and peritoneal reactions reported elsewhere. Nevertheless, important findings, probably applicable to other beta-adrenoreceptor antagonists, have emerged in relation to mortality and morbidity. (1) The practolol-treated group showed a significant reduction in overall mortality and in sudden deaths; (2) there was a highly significant reduction in \"all cardiac events\"; (3) the reduction in overall mortality was virtually confined to patients whose original pre-entry infarcts were sited anteriorly; (4) the protective effect of practolol was most evident in those patients with pre-entry anterior infarcts whose blood pressures at entry were below the mean for the trial as a whole; (5) there were highly significant group differences in favour of the drug relating to the incidence of angina pectoris and cardiac arrhythmias, and to the numbers of patients who had to be withdrawn from the trial because of these conditions; (6) significantly more patients were withdrawn from the treatment group because of suspected adverse reactions. It is concluded that practolol used in the long-term treatment of patients who have survived the acute phase of myocardial infarction reduces the death rate when the original infarct is sited anteriorly. It is postulated that the favourable results of the trial were due to beta-adrenoreceptor blockade rather than to some other property specific to practolol itself. Since practolol produces severe side effects in long-term use it is recommended that an alternative beta-adrenoreceptor blocking agent should be used.", "contents": "Improvement in prognosis of myocardial infarction by long-term beta-adrenoreceptor blockade using practolol. A multicentre international study. In a large-scale double-blind controlled trial of practolol (200 mg twice daily) in the long-term prophylactic treatment of 3038 patients recovering from acute myocardial infarction treatment was started one to four weeks after the acute attack. The trial was originally planned to include 4000 patients treated for at least a year but had to be terminated prematurely because of the serious oculocutaneous and peritoneal reactions reported elsewhere. Nevertheless, important findings, probably applicable to other beta-adrenoreceptor antagonists, have emerged in relation to mortality and morbidity. (1) The practolol-treated group showed a significant reduction in overall mortality and in sudden deaths; (2) there was a highly significant reduction in \"all cardiac events\"; (3) the reduction in overall mortality was virtually confined to patients whose original pre-entry infarcts were sited anteriorly; (4) the protective effect of practolol was most evident in those patients with pre-entry anterior infarcts whose blood pressures at entry were below the mean for the trial as a whole; (5) there were highly significant group differences in favour of the drug relating to the incidence of angina pectoris and cardiac arrhythmias, and to the numbers of patients who had to be withdrawn from the trial because of these conditions; (6) significantly more patients were withdrawn from the treatment group because of suspected adverse reactions. It is concluded that practolol used in the long-term treatment of patients who have survived the acute phase of myocardial infarction reduces the death rate when the original infarct is sited anteriorly. It is postulated that the favourable results of the trial were due to beta-adrenoreceptor blockade rather than to some other property specific to practolol itself. Since practolol produces severe side effects in long-term use it is recommended that an alternative beta-adrenoreceptor blocking agent should be used."}
{"id": "PMID:240484", "title": "Reversible changes in the accumulation and activities of tyrosine hydroxylase and dopamine-beta-hydroxylase in neurons of nucleus locus coeruleus during the retrograde reaction.", "content": "To examine the biochemical events associated with the retrograde reaction in central noradrenergic neurons, changes in the activities of several enzymes subserving the metabolism of catecholamines, including tyrosine hydroxylase (TH),dopamine-beta-hydroxylase (DBH), DOPA decarboxylase (DDC), and monoamine oxidase (MAO), were measured in the nucleus locus coeruleus of rat brain following transection of the ascending axons from neurons in this nucleus by electrolytic lesions of the posterolateral hypothalamus. Such lesions produced a triphasic response in the activities of TH and DBH consisting of: (a) an increase to approximately 150 percent of control during the first 48 h followed by (b) a reduction reaching 60 percent of control by day 14, and (c) a full recovery of activity by day 21-28. In contrast, the activities of DDC and MAO, enzymes non-specific for catecholamine neurons, were unchanged. Immunochemical titration with specific antibodies to TH and DBH demonstrated that the fall in enzyme activity was entirely attributable to reduced accumulation of specific enzyme protein and not inhibition of pre-existing enzyme molecules. There was no reduction in the number of neurons in the nucleus locus coeruleus as a consequence of the lesion. We conclude that a reduction in the accumulation of specific enzymes subserving transmitter biosynthesis characterizes a reversible retrograde reaction of central noradrenergic neurons. The coincidence of the time course of reduced enzyme accumulation with regenerative sprouting from damaged noradrenergic axons and also the absence of classical signs of chromatolysis in locus coeruleus neurons following comparable lesions suggest that, first, during the retrograde reaction there may be a reordering of priorities governing accumulation of specific proteins favoring accumulation of those required for reconstitution of cellular processes by sprouting at the expense of proteins utilized in the synthesis of neurotransmitters, and second, some intrinsic neurons of the CNS may undergo reversible biochemical changes of a retrograde reaction in the absence of the classical morphological appearance of chromatolysis.", "contents": "Reversible changes in the accumulation and activities of tyrosine hydroxylase and dopamine-beta-hydroxylase in neurons of nucleus locus coeruleus during the retrograde reaction. To examine the biochemical events associated with the retrograde reaction in central noradrenergic neurons, changes in the activities of several enzymes subserving the metabolism of catecholamines, including tyrosine hydroxylase (TH),dopamine-beta-hydroxylase (DBH), DOPA decarboxylase (DDC), and monoamine oxidase (MAO), were measured in the nucleus locus coeruleus of rat brain following transection of the ascending axons from neurons in this nucleus by electrolytic lesions of the posterolateral hypothalamus. Such lesions produced a triphasic response in the activities of TH and DBH consisting of: (a) an increase to approximately 150 percent of control during the first 48 h followed by (b) a reduction reaching 60 percent of control by day 14, and (c) a full recovery of activity by day 21-28. In contrast, the activities of DDC and MAO, enzymes non-specific for catecholamine neurons, were unchanged. Immunochemical titration with specific antibodies to TH and DBH demonstrated that the fall in enzyme activity was entirely attributable to reduced accumulation of specific enzyme protein and not inhibition of pre-existing enzyme molecules. There was no reduction in the number of neurons in the nucleus locus coeruleus as a consequence of the lesion. We conclude that a reduction in the accumulation of specific enzymes subserving transmitter biosynthesis characterizes a reversible retrograde reaction of central noradrenergic neurons. The coincidence of the time course of reduced enzyme accumulation with regenerative sprouting from damaged noradrenergic axons and also the absence of classical signs of chromatolysis in locus coeruleus neurons following comparable lesions suggest that, first, during the retrograde reaction there may be a reordering of priorities governing accumulation of specific proteins favoring accumulation of those required for reconstitution of cellular processes by sprouting at the expense of proteins utilized in the synthesis of neurotransmitters, and second, some intrinsic neurons of the CNS may undergo reversible biochemical changes of a retrograde reaction in the absence of the classical morphological appearance of chromatolysis."}
{"id": "PMID:240485", "title": "Localized catecholamine storage associated with granules in murine neuroblastoma cells.", "content": "Catecholamine storage was examined in cultures of the murine neuroblastoma cell line, N-TD6, using histofluorescence, electron microscopic, isotopic and radioautographic criteria. This line was originally derived from uncloned, C1300 tumor cells by selection in tyrosine deficient medium. N-TD6 cells possess both tyrosine hydroxylase (tyrosine-3-monooxygenase, EC 1.14.16.2) and dopamine beta-hydroxylase (dopamine beta-monooxygenase, EC 1.14.17.1) activities. When examined for paraformaldehyde-induced histofluorescence, a small percentage of cells in the population show intense catecholamine fluorescence, often localized within discrete regions of the cellular processes. Electron microscopic examination of these cells reveals both electron lucent vesicles and more frequent, electron dense granules, 50-70 nm and 100-300 nm in diameter, respectively. The distribution of these granules and vesicles varies, but they appear most numerous near the cell surface, along processes and within process endings. By labeling cells with [3H]dopamine and then allowing the cells to release unbound label in the presence of unlabeled dopamine, the localization of catecholamine stores was visualized by radioautographic techniques. While a variety of intracellular distribution of radioactivity were observed, the most prominent concentrations were found in the processes and their terminals; no labeled material was retained when reserpine was present during uptake. The topographic coincidence of granules, catecholamine fluorescence and [3H]dopamine retention in these neuroblastoma cells suggests that catecholamines are stored within these granules in a manner analogous to that observed in normal adrenergic neurons.", "contents": "Localized catecholamine storage associated with granules in murine neuroblastoma cells. Catecholamine storage was examined in cultures of the murine neuroblastoma cell line, N-TD6, using histofluorescence, electron microscopic, isotopic and radioautographic criteria. This line was originally derived from uncloned, C1300 tumor cells by selection in tyrosine deficient medium. N-TD6 cells possess both tyrosine hydroxylase (tyrosine-3-monooxygenase, EC 1.14.16.2) and dopamine beta-hydroxylase (dopamine beta-monooxygenase, EC 1.14.17.1) activities. When examined for paraformaldehyde-induced histofluorescence, a small percentage of cells in the population show intense catecholamine fluorescence, often localized within discrete regions of the cellular processes. Electron microscopic examination of these cells reveals both electron lucent vesicles and more frequent, electron dense granules, 50-70 nm and 100-300 nm in diameter, respectively. The distribution of these granules and vesicles varies, but they appear most numerous near the cell surface, along processes and within process endings. By labeling cells with [3H]dopamine and then allowing the cells to release unbound label in the presence of unlabeled dopamine, the localization of catecholamine stores was visualized by radioautographic techniques. While a variety of intracellular distribution of radioactivity were observed, the most prominent concentrations were found in the processes and their terminals; no labeled material was retained when reserpine was present during uptake. The topographic coincidence of granules, catecholamine fluorescence and [3H]dopamine retention in these neuroblastoma cells suggests that catecholamines are stored within these granules in a manner analogous to that observed in normal adrenergic neurons."}
{"id": "PMID:240491", "title": "A difference in sensitivity to alpha-adrenergic agonists exhibited by detrusor and bladder neck of rabbit.", "content": "In cumulative dose-response studies, strips from bladder neck of rabbit were significantly more sensitive to stimulation with noradrenaline, phenylephrine, and methoxamine than were strips from detrusor. There was no difference between the two regions in sensitivity to isoprenaline or carbachol. From the known characteristics of these agents, it seemed unlikely that metabolic destruction or uptake could account for the different sensitivities seen. Also, neither normetanephrine nor desmethylimipramine could alter significantly the potency of noradrenaline in either area of the bladder. It seems likely that the difference in sensitivity to alpha-adrenoceptor stimulation in the bladder neck and detrusor is due to factors at the receptor level.", "contents": "A difference in sensitivity to alpha-adrenergic agonists exhibited by detrusor and bladder neck of rabbit. In cumulative dose-response studies, strips from bladder neck of rabbit were significantly more sensitive to stimulation with noradrenaline, phenylephrine, and methoxamine than were strips from detrusor. There was no difference between the two regions in sensitivity to isoprenaline or carbachol. From the known characteristics of these agents, it seemed unlikely that metabolic destruction or uptake could account for the different sensitivities seen. Also, neither normetanephrine nor desmethylimipramine could alter significantly the potency of noradrenaline in either area of the bladder. It seems likely that the difference in sensitivity to alpha-adrenoceptor stimulation in the bladder neck and detrusor is due to factors at the receptor level."}
{"id": "PMID:240492", "title": "Early effects of aminonucleoside on enzymes in the Golgi apparatus of rat liver.", "content": "Rats were injected with a single intravenous dose of aminonucleoside (AMN) and sacrificed 1-48 h later. The activity of several enzymes was assayed in the Golgi apparatus isolated from the liver. Galactosyltransferase activity showed little changes after the AMN, but both acid (EC 3.1.3.2) and alkaline phosphatase (EC 3.1.3.1) activities increased within the first hour and reached control levels only 5-24 h later. Thiamine pyrophosphatase and arylsulfatase A (EC 3.1.6.1) activities also increased and stayed at higher levels for the duration of the experiment. Arylsulfatase B (EC 3.1.6.1) activity decreased shortly after the AMN but later increased to above control levels. These findings support earlier results in which liver ultrastructural and biochemical changes were observed early before renal lesions and proteinuria.", "contents": "Early effects of aminonucleoside on enzymes in the Golgi apparatus of rat liver. Rats were injected with a single intravenous dose of aminonucleoside (AMN) and sacrificed 1-48 h later. The activity of several enzymes was assayed in the Golgi apparatus isolated from the liver. Galactosyltransferase activity showed little changes after the AMN, but both acid (EC 3.1.3.2) and alkaline phosphatase (EC 3.1.3.1) activities increased within the first hour and reached control levels only 5-24 h later. Thiamine pyrophosphatase and arylsulfatase A (EC 3.1.6.1) activities also increased and stayed at higher levels for the duration of the experiment. Arylsulfatase B (EC 3.1.6.1) activity decreased shortly after the AMN but later increased to above control levels. These findings support earlier results in which liver ultrastructural and biochemical changes were observed early before renal lesions and proteinuria."}
{"id": "PMID:240493", "title": "Regional cerebral blood flow of the rat in acute carbon monoxide intoxication.", "content": "The effect of carbon monoxide (CO) on the regional cerebral blood flow was studied by exposing lightly anesthetized rats for 30 min to 0.5, 1.0, 1.5, and 2.0% CO gas mixtures. Cortical cerebral blood flow (CBF) increases of near 200%, 300%, and 400% control were observed at 0.5, 1.0, and 1.5% CO, respectively; whereas at 2.0% CO a reversal of the CBF increase was observed with values declining to near 300% control. The CBF response of subcortical, cerebellar, and brain stem areas was quantitatively similar to that of cortex, indicating that the CBF changes in CO intoxication are general. The decrease in CBF at 2.0% CO was related to significant decreases in arterial CO2 tension. Comparison of the CBF data to previous metabolic results in CO poisoning suggests that the CBF increases are a principal factor in the maintenance of an intact energy state in CO poisoning.", "contents": "Regional cerebral blood flow of the rat in acute carbon monoxide intoxication. The effect of carbon monoxide (CO) on the regional cerebral blood flow was studied by exposing lightly anesthetized rats for 30 min to 0.5, 1.0, 1.5, and 2.0% CO gas mixtures. Cortical cerebral blood flow (CBF) increases of near 200%, 300%, and 400% control were observed at 0.5, 1.0, and 1.5% CO, respectively; whereas at 2.0% CO a reversal of the CBF increase was observed with values declining to near 300% control. The CBF response of subcortical, cerebellar, and brain stem areas was quantitatively similar to that of cortex, indicating that the CBF changes in CO intoxication are general. The decrease in CBF at 2.0% CO was related to significant decreases in arterial CO2 tension. Comparison of the CBF data to previous metabolic results in CO poisoning suggests that the CBF increases are a principal factor in the maintenance of an intact energy state in CO poisoning."}
{"id": "PMID:240494", "title": "The mode of spontaneous transmitter release at the insect neuromuscular junction.", "content": "The time intervals between miniature excitatory postsynaptic potentials and the counts of them in the cockroach, Periplaneta americana, were analyzed, using a computer program to test for properties of a Poisson process. The miniature potentials occurred basically in random manner at this neuromuscular junction. Although the distribution of the potentials did not fit the criteria for a Poisson process when the muscle fiber exhibited the short burst of high-frequency discharges, it was suggested that the primary process of such a distribution is Poisson, which is occasionally contaminated by the burst phase of the release rates.", "contents": "The mode of spontaneous transmitter release at the insect neuromuscular junction. The time intervals between miniature excitatory postsynaptic potentials and the counts of them in the cockroach, Periplaneta americana, were analyzed, using a computer program to test for properties of a Poisson process. The miniature potentials occurred basically in random manner at this neuromuscular junction. Although the distribution of the potentials did not fit the criteria for a Poisson process when the muscle fiber exhibited the short burst of high-frequency discharges, it was suggested that the primary process of such a distribution is Poisson, which is occasionally contaminated by the burst phase of the release rates."}
{"id": "PMID:240495", "title": "A modifier mutation affecting utilization of mannitol in pneumococcus.", "content": "The altered growth of a pneumococcal mutant containing marker M, which confers ability to utilize mannitol, and a modifier gene is reported. The modifier gene is closely linked to the M gene and imposes a requirement for growth in 0.4% glucose before growth in mannitol medium. The tentative position of the M gene of pneumococcus is ery-r str-r M sul-rd.", "contents": "A modifier mutation affecting utilization of mannitol in pneumococcus. The altered growth of a pneumococcal mutant containing marker M, which confers ability to utilize mannitol, and a modifier gene is reported. The modifier gene is closely linked to the M gene and imposes a requirement for growth in 0.4% glucose before growth in mannitol medium. The tentative position of the M gene of pneumococcus is ery-r str-r M sul-rd."}
{"id": "PMID:240496", "title": "Biochemical changes during sporulation of Bacillus stearothermophilus.", "content": "The process of sporulation was studied in Bacillus stearothermophilus. A medium is described that supports good growth and sporulation of the organism. In this medium, which contains glucose, salts, and amino acids, acetate starts to accumulate before any of the glucose is catabolized. Enzymes of the tricarboxylic acid cycle are present at all times during growth and sporulation and are found in dormant spores. As the glucose in the culture is consumed, acetate rapidly increases and the pH of the medium drops. The acetate rapidly disappears during sporulation and the pH rises. Dipicolinic acid appears during sporulation and several key-enzyme activities fluctuate in a characteristic pattern.", "contents": "Biochemical changes during sporulation of Bacillus stearothermophilus. The process of sporulation was studied in Bacillus stearothermophilus. A medium is described that supports good growth and sporulation of the organism. In this medium, which contains glucose, salts, and amino acids, acetate starts to accumulate before any of the glucose is catabolized. Enzymes of the tricarboxylic acid cycle are present at all times during growth and sporulation and are found in dormant spores. As the glucose in the culture is consumed, acetate rapidly increases and the pH of the medium drops. The acetate rapidly disappears during sporulation and the pH rises. Dipicolinic acid appears during sporulation and several key-enzyme activities fluctuate in a characteristic pattern."}
{"id": "PMID:240497", "title": "Influence of albumin on rubella virus hemagglutination and the hemagglutination-inhibition test.", "content": "The HEPES-saline-albumin-gelatin (HSAG) diluent found optimal for agglutination of fowl erythrocytes by rubella virus antigen is also optimal for agglutination of trypsin-treated human group O cells. Albumins from different commercial sources, however, can have varying inhibitory effects on rubella hemagglutination titers. This can have a significant effect on the hemagglutination-inhibition test since antibody titers measured by this procedure are related to the amount of antigen used.", "contents": "Influence of albumin on rubella virus hemagglutination and the hemagglutination-inhibition test. The HEPES-saline-albumin-gelatin (HSAG) diluent found optimal for agglutination of fowl erythrocytes by rubella virus antigen is also optimal for agglutination of trypsin-treated human group O cells. Albumins from different commercial sources, however, can have varying inhibitory effects on rubella hemagglutination titers. This can have a significant effect on the hemagglutination-inhibition test since antibody titers measured by this procedure are related to the amount of antigen used."}
{"id": "PMID:240498", "title": "The development of an increased rate of Cl- uptake in the ascomycete Neocosmospora vasinfecta.", "content": "Freshly harvested mycelium of the filamentous ascomycete Neocosmospora vasinfecta accumulated C1- against a concentration gradient by a process probably requiring the expenditure of metabolic energy. When mycelium, washed free of growth medium, was incubated in deionized water or tris (hydroxymethyl) aminomethane sulfate at pH 7.5 for 4 h and then transferred to K36C1 solutions, the C1- uptake rate was, on the average, 3.77 +/- 0.26 (+/-SE, N = 20) times the uptake rate exhibited by freshly harvested mycelium. This development of an increased rate of Cl- uptake could be blocked by the presence of an inhibitor of ribonucleic acid synthesis (azaguanine) or of protein synthesis (cycloheximide, fluorophenylalanine, or puromycin). The combined presence of glucose and a potassium salt in the preincubation solution virtually arrested the development of enhanced Cl- uptake. The rate of Cl- uptake by freshly harvested mycelium did not vary greatly with the age of the culture on harvest but the ability to develop an increased rate declined with age. The fact that it is possible to obtain mycelium possessing widely different capacities for Cl- uptake should assist in biochemical characterization of the Cl- uptake system.", "contents": "The development of an increased rate of Cl- uptake in the ascomycete Neocosmospora vasinfecta. Freshly harvested mycelium of the filamentous ascomycete Neocosmospora vasinfecta accumulated C1- against a concentration gradient by a process probably requiring the expenditure of metabolic energy. When mycelium, washed free of growth medium, was incubated in deionized water or tris (hydroxymethyl) aminomethane sulfate at pH 7.5 for 4 h and then transferred to K36C1 solutions, the C1- uptake rate was, on the average, 3.77 +/- 0.26 (+/-SE, N = 20) times the uptake rate exhibited by freshly harvested mycelium. This development of an increased rate of Cl- uptake could be blocked by the presence of an inhibitor of ribonucleic acid synthesis (azaguanine) or of protein synthesis (cycloheximide, fluorophenylalanine, or puromycin). The combined presence of glucose and a potassium salt in the preincubation solution virtually arrested the development of enhanced Cl- uptake. The rate of Cl- uptake by freshly harvested mycelium did not vary greatly with the age of the culture on harvest but the ability to develop an increased rate declined with age. The fact that it is possible to obtain mycelium possessing widely different capacities for Cl- uptake should assist in biochemical characterization of the Cl- uptake system."}
{"id": "PMID:240499", "title": "Biological characteristics of an enterotoxin produced by Bacillus cereus.", "content": "An enterotoxin synthesized during exponential growth by Bacillus cereus produces fluid accumulation in rabbit ileal loops, alters vascular permeability in the skin of rabbits, and kills mice when injected intravenously. All activities are eluted simultaneously from a Sephadex G-75 column and are distinct from the hemolysin and egg yolk turbidity factor of B. cereus. The enterotoxin is a true exotoxin. It interacts with intestinal receptor sites in a highly transient manner in the ileal loop system. Rabbit immune serum produced against the culture fluids from one strain of B. cereus neutralized the three biological activities in all other strains tested except strain B-6-ac for which none of the activities were neutralized. Enterotoxin proved to be unstable under a wide variety of conditions; ionic strength was especially critical. Enterotoxin was most stable in a pH range of 5.0 to 10.0, but lost activity rapidly outside this range. Alkylation provided some protection of enterotoxin activity in crude preparations but failed to protect activity during purification procedures. It did not appear to affect critically the enterotoxin molecule itself, since elution profiles on Sephadex G-75 chromatography were unchanged after alkylation.", "contents": "Biological characteristics of an enterotoxin produced by Bacillus cereus. An enterotoxin synthesized during exponential growth by Bacillus cereus produces fluid accumulation in rabbit ileal loops, alters vascular permeability in the skin of rabbits, and kills mice when injected intravenously. All activities are eluted simultaneously from a Sephadex G-75 column and are distinct from the hemolysin and egg yolk turbidity factor of B. cereus. The enterotoxin is a true exotoxin. It interacts with intestinal receptor sites in a highly transient manner in the ileal loop system. Rabbit immune serum produced against the culture fluids from one strain of B. cereus neutralized the three biological activities in all other strains tested except strain B-6-ac for which none of the activities were neutralized. Enterotoxin proved to be unstable under a wide variety of conditions; ionic strength was especially critical. Enterotoxin was most stable in a pH range of 5.0 to 10.0, but lost activity rapidly outside this range. Alkylation provided some protection of enterotoxin activity in crude preparations but failed to protect activity during purification procedures. It did not appear to affect critically the enterotoxin molecule itself, since elution profiles on Sephadex G-75 chromatography were unchanged after alkylation."}
{"id": "PMID:240500", "title": "A microplaque reduction assay for human and mouse interferon.", "content": "A microplaque reduction assay for human and mouse interferons is described, using plastic disposable multicompartmental plates with flat-bottomed wells of 6 mm in diameter. The procedure is rapid and reproducible and lends itself to a considerable degree of automation. Its potential application in other areas of virology, such as rapid screening of samples for virus content or assay of neutralizing antibodies, is also discussed.", "contents": "A microplaque reduction assay for human and mouse interferon. A microplaque reduction assay for human and mouse interferons is described, using plastic disposable multicompartmental plates with flat-bottomed wells of 6 mm in diameter. The procedure is rapid and reproducible and lends itself to a considerable degree of automation. Its potential application in other areas of virology, such as rapid screening of samples for virus content or assay of neutralizing antibodies, is also discussed."}
{"id": "PMID:240501", "title": "Assembly of the enveloped bacteriophage phi 6 in environments which perturb the host cell membranes.", "content": "The effects of known membrane-perturbing agents (pH, Na+, Ca2+, and a small lipid-soluble molecule) on the enveloped bacteriophage phi 6 host cell system were investigated at the levels of cellular growth, virus assembly and stability, and the physical and chemical properties of host cell membranes. Spin-label probes of cellular membranes indicate that growth in high levels of Na+ or the small spherical hydrophobic molecule adamantanone results in membranes having increased \"fluidity,\" while growth in high levels of Ca2+ results in slightly greater rigidity of the membranes. In addition, the phospholipid composition of the cellular membranes is dependent on the NaCl concentration in the growth medium. None of these membrane alterations, however, prevent the production of infectious phi 6 virus particles.", "contents": "Assembly of the enveloped bacteriophage phi 6 in environments which perturb the host cell membranes. The effects of known membrane-perturbing agents (pH, Na+, Ca2+, and a small lipid-soluble molecule) on the enveloped bacteriophage phi 6 host cell system were investigated at the levels of cellular growth, virus assembly and stability, and the physical and chemical properties of host cell membranes. Spin-label probes of cellular membranes indicate that growth in high levels of Na+ or the small spherical hydrophobic molecule adamantanone results in membranes having increased \"fluidity,\" while growth in high levels of Ca2+ results in slightly greater rigidity of the membranes. In addition, the phospholipid composition of the cellular membranes is dependent on the NaCl concentration in the growth medium. None of these membrane alterations, however, prevent the production of infectious phi 6 virus particles."}
{"id": "PMID:240503", "title": "Role of cyclic AMP in differentiation of human neuroblastoma cells in culture.", "content": "The inhibitors of cyclic AMP phosphodiesterase (papaverine and 4-(-3-butoxy-4-methoxybenzyl)-2-imidazolidinone), serum-free medium, and x irradiation caused cell death and neurite formation in human neuroblastoma cells in culture (IMR-32), whereas theophylline was ineffective. Prostaglandin (PG) E1, N6O'2-dibutyryl adenosine 3',5'-cyclic monophosphate (dbcAMP) induced neurites without causing cell lethality. Inhibitors of phosphodiesterase and PGE1 increased the intracellular level of cAMP by about 2- and 4-fold respectively, whereas serum-free medium and x irradiation did not. The combination of PGE1 and phosphodiesterase inhibitor was more effective in causing morphological differentiation and in increasing the cAMP level than the individual agent. Sodium butyrate induced cell death and neurites, probably in part by increasing the cAMP level. cAMP, guanosine 3',5'-cyclic monophosphate, and adenosine had no detectable effect on the growth or morphology of neuroblastoma cells in culture. Adenosine 5'-monophosphate produced cell death without causing neurite formation. DbcAMP, and to a much lesser degree, sodium butyrate increased the tyrosine hydroxylase activity.", "contents": "Role of cyclic AMP in differentiation of human neuroblastoma cells in culture. The inhibitors of cyclic AMP phosphodiesterase (papaverine and 4-(-3-butoxy-4-methoxybenzyl)-2-imidazolidinone), serum-free medium, and x irradiation caused cell death and neurite formation in human neuroblastoma cells in culture (IMR-32), whereas theophylline was ineffective. Prostaglandin (PG) E1, N6O'2-dibutyryl adenosine 3',5'-cyclic monophosphate (dbcAMP) induced neurites without causing cell lethality. Inhibitors of phosphodiesterase and PGE1 increased the intracellular level of cAMP by about 2- and 4-fold respectively, whereas serum-free medium and x irradiation did not. The combination of PGE1 and phosphodiesterase inhibitor was more effective in causing morphological differentiation and in increasing the cAMP level than the individual agent. Sodium butyrate induced cell death and neurites, probably in part by increasing the cAMP level. cAMP, guanosine 3',5'-cyclic monophosphate, and adenosine had no detectable effect on the growth or morphology of neuroblastoma cells in culture. Adenosine 5'-monophosphate produced cell death without causing neurite formation. DbcAMP, and to a much lesser degree, sodium butyrate increased the tyrosine hydroxylase activity."}
{"id": "PMID:240505", "title": "Glutamine production by the isolated perfused rat heart during ammonium chloride perfusion.", "content": "Myocardial levels of ammonia, glutamate, and glutamine and the release of glutamate and glutamine were studied in the isolated perfused rat heart during perfusion with ammonium chloride, epinephrine, and conditions of anoxia or ischaemia. Perfusion for 15 min with effective ammonium chloride concentrations of 0.53, 0.71, and 2.06 mmol/l resulted in glutamine production of 1.34, 0.95, and 4.41 mmol with 15 min-1/200 dry weight compatible with the presence of glutamine synthetase in rat myocardium. Myocardial ammonium content was unchanged by perfusion with 0.53 and 0.71 mmol/l ammonium chloride, but was increased by 1.36 mumol with 15 min-1/200 mg dry weight by perfusion with 2.06 mmol/l ammonium chloride. Increased myocardial contents of ammonia and glutamine were not accompanied by depression of left ventricular pressure. Perfusion with epinephrine (0.20 mug/ml) resulted in an increased myocardial content of glutamine. Anoxia or ischaemia resulted in no changes in ammonia content, and no changes in glutamine or glutamate production. The net release of glutamine into the perfusate was about 10 times the net release of glutamate.", "contents": "Glutamine production by the isolated perfused rat heart during ammonium chloride perfusion. Myocardial levels of ammonia, glutamate, and glutamine and the release of glutamate and glutamine were studied in the isolated perfused rat heart during perfusion with ammonium chloride, epinephrine, and conditions of anoxia or ischaemia. Perfusion for 15 min with effective ammonium chloride concentrations of 0.53, 0.71, and 2.06 mmol/l resulted in glutamine production of 1.34, 0.95, and 4.41 mmol with 15 min-1/200 dry weight compatible with the presence of glutamine synthetase in rat myocardium. Myocardial ammonium content was unchanged by perfusion with 0.53 and 0.71 mmol/l ammonium chloride, but was increased by 1.36 mumol with 15 min-1/200 mg dry weight by perfusion with 2.06 mmol/l ammonium chloride. Increased myocardial contents of ammonia and glutamine were not accompanied by depression of left ventricular pressure. Perfusion with epinephrine (0.20 mug/ml) resulted in an increased myocardial content of glutamine. Anoxia or ischaemia resulted in no changes in ammonia content, and no changes in glutamine or glutamate production. The net release of glutamine into the perfusate was about 10 times the net release of glutamate."}
{"id": "PMID:240507", "title": "Endocytosis and multivesicular body formation in rabbit luteal cells during pseudopregnancy.", "content": "Horseradish peroxidase (HRP) was injected directly into the corpora lutea of rabbits on different days of pseudopregnancy. Young luteal cells have also been incubated \"in vitro\" in a medium containing horseradish peroxidase. In the \"in vivo\" experiments the 5 to 9 days old luteal cells take up far more horseradish peroxidase than the older ones (14-20 days). Different types of endocytic vacuoles, MvB's and also some DB's are already peroxidase positive shortly (15-20 min) after injection of the tracer. In the \"in vitro\" experiments the cells are more heavily loaded. The normal morphology of pale, dense and terminal MvB's is also described and staining with PTA at low pH provides further information on changes occurring in the MvB's. The various findings on multivesicular bodies are compared and two possible pathways for endocytic vacuoles are proposed: one to DB's the other to MvB's. The related phenomena of the uptake of material and the internalization of plasma membrane are discussed in the light of the possible function of endocytosis in luteal cells.", "contents": "Endocytosis and multivesicular body formation in rabbit luteal cells during pseudopregnancy. Horseradish peroxidase (HRP) was injected directly into the corpora lutea of rabbits on different days of pseudopregnancy. Young luteal cells have also been incubated \"in vitro\" in a medium containing horseradish peroxidase. In the \"in vivo\" experiments the 5 to 9 days old luteal cells take up far more horseradish peroxidase than the older ones (14-20 days). Different types of endocytic vacuoles, MvB's and also some DB's are already peroxidase positive shortly (15-20 min) after injection of the tracer. In the \"in vitro\" experiments the cells are more heavily loaded. The normal morphology of pale, dense and terminal MvB's is also described and staining with PTA at low pH provides further information on changes occurring in the MvB's. The various findings on multivesicular bodies are compared and two possible pathways for endocytic vacuoles are proposed: one to DB's the other to MvB's. The related phenomena of the uptake of material and the internalization of plasma membrane are discussed in the light of the possible function of endocytosis in luteal cells."}
{"id": "PMID:240509", "title": "[Specificity of action of phospholipases of rat intestinal mucosa].", "content": "The total homogenate of rat intestine is devoid of C or D phospholipase activity. At pH 6,5 in the presence of phosphatidylcholines, it exhibits a B phospholipase activity and in the presence of exogen lysophosphatidylcholines an A1 lysophospholipase activity. At pH 8,5 the intestinal mucous membrane of a rat shows an isolated A2 phospholipase activity.", "contents": "[Specificity of action of phospholipases of rat intestinal mucosa]. The total homogenate of rat intestine is devoid of C or D phospholipase activity. At pH 6,5 in the presence of phosphatidylcholines, it exhibits a B phospholipase activity and in the presence of exogen lysophosphatidylcholines an A1 lysophospholipase activity. At pH 8,5 the intestinal mucous membrane of a rat shows an isolated A2 phospholipase activity."}
{"id": "PMID:240512", "title": "Acidification of plasma by the red cell due to radiographic contrast materials.", "content": "The effect of water-soluble radiographic contrast material on pH when added to blood in clinical dosages in vitro or when used in vivo for diagnostic purposes was examined. Contrast material caused a reduction of blood pH. The mechanism of this occurence was found to be the balancing of the negative charge of intracellular organic anions by the extracellular anionic contrast material molecules. The normal negative potential of about 10 mV across the red cell membrane was reduced, nullified, or reversed depending on the concentration of contrast material added to blood. As the inside of the cell became more positive with respect to the outside, protons were, in effect, repelled into plasma, although the apparent exodus of protons occurs by the generation and outward diffusion of carbon dioxide. Since the acidemia is dependent on rehydration of carbon dioxide in plasma, a reaction measured in seconds, the site of injection and transit time of dye will contribute to the pH of the plasma during passage through a regional capillary bed. We speculate that an alteration in membrane potential and/or the acute acidemia may contribute to the adverse effects of contrast material, particularly on tissues dependent on membrane electrical rhythmicity such as the myocardium.", "contents": "Acidification of plasma by the red cell due to radiographic contrast materials. The effect of water-soluble radiographic contrast material on pH when added to blood in clinical dosages in vitro or when used in vivo for diagnostic purposes was examined. Contrast material caused a reduction of blood pH. The mechanism of this occurence was found to be the balancing of the negative charge of intracellular organic anions by the extracellular anionic contrast material molecules. The normal negative potential of about 10 mV across the red cell membrane was reduced, nullified, or reversed depending on the concentration of contrast material added to blood. As the inside of the cell became more positive with respect to the outside, protons were, in effect, repelled into plasma, although the apparent exodus of protons occurs by the generation and outward diffusion of carbon dioxide. Since the acidemia is dependent on rehydration of carbon dioxide in plasma, a reaction measured in seconds, the site of injection and transit time of dye will contribute to the pH of the plasma during passage through a regional capillary bed. We speculate that an alteration in membrane potential and/or the acute acidemia may contribute to the adverse effects of contrast material, particularly on tissues dependent on membrane electrical rhythmicity such as the myocardium."}
{"id": "PMID:240513", "title": "Effects of buffers on aspartate aminotransferase activity and association of the enzyme with pyridoxal phosphate.", "content": "Using purified enzymes of human origin and patients' sera, we examined factors influencing the in vitro association of pyridoxal phosphate with aspartate aminotransferase (EC 2.6.1.1). The rate of association was markedly retarded by phosphate buffer in comparison with tris(hydroxymethyl)aminomethane or six other buffers. Pyridoxal phosphate at an incubation concentration of 130 mumol/liter reactivated the entire apoenzyme portion of an apoenzyme/holoenzyme mixture within 5 min in tris(hydroxymethyl)aminomethane; in contrast, less than 20% was associated during 15 min in phosphate. Activity measured in tris(hydroxymethyl)aminomethane-buffer without exogenous pyridoxal phosphate was 4% greater than that in phosphate and was slightly increased by increasing the pH of the assay mixture from 7.5 to 8.0. Aspartate in the incubation medium did not retard the stimulation in tris(hydroxymethyl)aminomethane buffer. While the magnitude of stimulation varied greatly among sera, a consistent mean stimulation of 30% for groups of sera with normal activities was found when asparate at 125 mmol/liter, 2-oxoglutarate at 6.7 mmol/liter and tris(hydroxymethyl)aminomethane at 90 mmol/liter were used, an increase over the 16% with phosphate buffer [Clin. Chem. 19, 92 (1973)]. Absorbance spectra suggest pyridoxal phosphate exists as the Schiff base of tris(hydroxymethyl)aminomethane or aspartate, or both, under conditions of assay incubation (without addition of  2-oxoglutarate). Nonenzymatic catalysis of the reaction by pyridoxal phosphate alone or a formation of a protein/pyridoxal phosphate adduct was discounted with use of a D-asparate substrates.", "contents": "Effects of buffers on aspartate aminotransferase activity and association of the enzyme with pyridoxal phosphate. Using purified enzymes of human origin and patients' sera, we examined factors influencing the in vitro association of pyridoxal phosphate with aspartate aminotransferase (EC 2.6.1.1). The rate of association was markedly retarded by phosphate buffer in comparison with tris(hydroxymethyl)aminomethane or six other buffers. Pyridoxal phosphate at an incubation concentration of 130 mumol/liter reactivated the entire apoenzyme portion of an apoenzyme/holoenzyme mixture within 5 min in tris(hydroxymethyl)aminomethane; in contrast, less than 20% was associated during 15 min in phosphate. Activity measured in tris(hydroxymethyl)aminomethane-buffer without exogenous pyridoxal phosphate was 4% greater than that in phosphate and was slightly increased by increasing the pH of the assay mixture from 7.5 to 8.0. Aspartate in the incubation medium did not retard the stimulation in tris(hydroxymethyl)aminomethane buffer. While the magnitude of stimulation varied greatly among sera, a consistent mean stimulation of 30% for groups of sera with normal activities was found when asparate at 125 mmol/liter, 2-oxoglutarate at 6.7 mmol/liter and tris(hydroxymethyl)aminomethane at 90 mmol/liter were used, an increase over the 16% with phosphate buffer [Clin. Chem. 19, 92 (1973)]. Absorbance spectra suggest pyridoxal phosphate exists as the Schiff base of tris(hydroxymethyl)aminomethane or aspartate, or both, under conditions of assay incubation (without addition of  2-oxoglutarate). Nonenzymatic catalysis of the reaction by pyridoxal phosphate alone or a formation of a protein/pyridoxal phosphate adduct was discounted with use of a D-asparate substrates."}
{"id": "PMID:240514", "title": "Fluorometric enzymatic determination of total cholesterol in serum.", "content": "We describe a fluorometric enzymatic method for determining total serum cholesterol, based on hydrolysis of cholesterol esters to free cholesterol by cholesterol ester hydrolase (EC 3.1.1.13). The free cholesterol formed, as well as that initially present, is then oxidized by cholesterol oxidase (EC 1.1.3.6) to cholest-4-en-3-one with simultaneous production of hydrogen peroxide. The latter catalytically oxidizes homovanillic acid in the presence of peroxidase (EC 1.11.1.7) to form the highly fluorescent 2,2'-dihydroxy-3,3'-dimethoxy-biphenyl-5,5'-diacetic acid. A calibration curve is constructed from data on a series of standard cholesterol solutions vs. the corresponding fluorescence change (deltaf/5 min). This curve is linear up to 4.0 g of total serum cholesterol per liter of serum. The method is specific, precise, accurate, rapid, and simple, and results correlate well with those obtained by both the Liebermann-Burchard procedure and the colorimetric enzymatic method (correlation coefficients, 0.984 and 0.981, respectively).", "contents": "Fluorometric enzymatic determination of total cholesterol in serum. We describe a fluorometric enzymatic method for determining total serum cholesterol, based on hydrolysis of cholesterol esters to free cholesterol by cholesterol ester hydrolase (EC 3.1.1.13). The free cholesterol formed, as well as that initially present, is then oxidized by cholesterol oxidase (EC 1.1.3.6) to cholest-4-en-3-one with simultaneous production of hydrogen peroxide. The latter catalytically oxidizes homovanillic acid in the presence of peroxidase (EC 1.11.1.7) to form the highly fluorescent 2,2'-dihydroxy-3,3'-dimethoxy-biphenyl-5,5'-diacetic acid. A calibration curve is constructed from data on a series of standard cholesterol solutions vs. the corresponding fluorescence change (deltaf/5 min). This curve is linear up to 4.0 g of total serum cholesterol per liter of serum. The method is specific, precise, accurate, rapid, and simple, and results correlate well with those obtained by both the Liebermann-Burchard procedure and the colorimetric enzymatic method (correlation coefficients, 0.984 and 0.981, respectively)."}
{"id": "PMID:240515", "title": "Reaction-rate assay of serum sorbitol dehydrogenase activity of 37 degrees C.", "content": "The sorbitol dehydrogenase (EC 1.1.1.14) activity of human serum and liver was investigated at 37 degrees C. Various buffers were examined but tris(hydroxymethyl)aminomethane HCI in a final concentration of 90 mmol/liter (pH 6.6, at 37 degrees C) was the one with which activity was the greatest. The enzyme is inhibited by its substrate, D-fructose, and activity was greatest with a substrate concentration (in the final assay mixture) of 500 mmol/liter and an NADH concentration of 247 mumol/liter. The specimen volume was 100 mul. The enzyme from liver and serum was shown to have similar Km values and activation energies, and we conclude that the liver enzyme was unchanged on passing into the extrahepatic space. Normal values for this assay are 0--2.6 U/liter (2.5 and 97.5 percentiles).", "contents": "Reaction-rate assay of serum sorbitol dehydrogenase activity of 37 degrees C. The sorbitol dehydrogenase (EC 1.1.1.14) activity of human serum and liver was investigated at 37 degrees C. Various buffers were examined but tris(hydroxymethyl)aminomethane HCI in a final concentration of 90 mmol/liter (pH 6.6, at 37 degrees C) was the one with which activity was the greatest. The enzyme is inhibited by its substrate, D-fructose, and activity was greatest with a substrate concentration (in the final assay mixture) of 500 mmol/liter and an NADH concentration of 247 mumol/liter. The specimen volume was 100 mul. The enzyme from liver and serum was shown to have similar Km values and activation energies, and we conclude that the liver enzyme was unchanged on passing into the extrahepatic space. Normal values for this assay are 0--2.6 U/liter (2.5 and 97.5 percentiles)."}
{"id": "PMID:240516", "title": "Simple, sensitive method for measuring plasmin and plasminogen activity in plasma.", "content": "We describe a sensitive, simple, and rapid method for measuring plasmin and plasminogen in plasma, with fibrinogen as substrate. The assay can be done within 1 h. Plasma is diluted 20-fold with buffer and 0.1 ml (5 mul of original plasma) is incubated for 5 min at 37 degrees C, with or without 400 units of streptokinase. Then 2.0 ml of fibrinogen solution is added, the mixture again incubated (37 degrees C, 5 min), and the reaction stopped. The amount of tyrosine liberated from the fibrinogen is measured and is related to activity. This method is suitable for routine clinical work if the same batch of fibrinogen is used.", "contents": "Simple, sensitive method for measuring plasmin and plasminogen activity in plasma. We describe a sensitive, simple, and rapid method for measuring plasmin and plasminogen in plasma, with fibrinogen as substrate. The assay can be done within 1 h. Plasma is diluted 20-fold with buffer and 0.1 ml (5 mul of original plasma) is incubated for 5 min at 37 degrees C, with or without 400 units of streptokinase. Then 2.0 ml of fibrinogen solution is added, the mixture again incubated (37 degrees C, 5 min), and the reaction stopped. The amount of tyrosine liberated from the fibrinogen is measured and is related to activity. This method is suitable for routine clinical work if the same batch of fibrinogen is used."}
{"id": "PMID:240511", "title": "[Autoxidation rate increase of linoleic acid in the presence of tocopherol in aqueous medium ; study of the transformation of tocopherol].", "content": "Linoleic acid in aqueous emulsion is spontaneously autoxidized and product hydroperoxides. In vitro the autoxidation of the cis-9, cis-12, octadecadienoic acid with DL-alpha-tocopherol, both emulsified in water, shows an important increase of the hydroperoxides. During this time the tocopherol quickly disappears.", "contents": "[Autoxidation rate increase of linoleic acid in the presence of tocopherol in aqueous medium ; study of the transformation of tocopherol]. Linoleic acid in aqueous emulsion is spontaneously autoxidized and product hydroperoxides. In vitro the autoxidation of the cis-9, cis-12, octadecadienoic acid with DL-alpha-tocopherol, both emulsified in water, shows an important increase of the hydroperoxides. During this time the tocopherol quickly disappears."}
{"id": "PMID:240517", "title": "The heterogeneity of the serum activity of gamma-glutamyl transpeptidase in hepatobiliary diseases as studied by agarose gel electrophoresis.", "content": "Using electrophoresis on agarose gel, the serum activity of gamma-GT in various hepatobiliary diseases has been separated into several electrophoretic fractions. Predominance of activity was always found in fractions corresponding to either alpha1-, alpha2- or beta-globulins. The predominant activity fractions have been related to the various disease states and to the zymogram patterns of gamma-GT found in bile and tissue homogenates of liver, bile duct and pancreas. Bile disclosed activity in the beta-region, tissue homogenates of liver mostly in the alpha1- and alpha2- areas, bile dict showed very faint activity in the alpha1- position, while extracts of pancreas revealed activity in the regions of alpha2, alpha2-beta and beta-gamma. In serum, dominance of alpha1-activity was found in all cases associated with alcoholism and alcoholic cirrhosis, this activity also appeared as the most frequent dominant one in biliary obstruction. Predominance of alpha2 and/or the beta-fraction in most cases occurred associated with malignant processes involving liver and/or pancreas.", "contents": "The heterogeneity of the serum activity of gamma-glutamyl transpeptidase in hepatobiliary diseases as studied by agarose gel electrophoresis. Using electrophoresis on agarose gel, the serum activity of gamma-GT in various hepatobiliary diseases has been separated into several electrophoretic fractions. Predominance of activity was always found in fractions corresponding to either alpha1-, alpha2- or beta-globulins. The predominant activity fractions have been related to the various disease states and to the zymogram patterns of gamma-GT found in bile and tissue homogenates of liver, bile duct and pancreas. Bile disclosed activity in the beta-region, tissue homogenates of liver mostly in the alpha1- and alpha2- areas, bile dict showed very faint activity in the alpha1- position, while extracts of pancreas revealed activity in the regions of alpha2, alpha2-beta and beta-gamma. In serum, dominance of alpha1-activity was found in all cases associated with alcoholism and alcoholic cirrhosis, this activity also appeared as the most frequent dominant one in biliary obstruction. Predominance of alpha2 and/or the beta-fraction in most cases occurred associated with malignant processes involving liver and/or pancreas."}
{"id": "PMID:240518", "title": "Rapid fluorimetric determination of 5-fluorocytosine in serum.", "content": "A rapid fluorimetric procedure for the determination of the fungicide 5-fluorocytosine in serum is described. The method is high in precision (S.D. 1.6 mug/ml at 50 mug/ml) and specificity and can be performed in 60-90 minutes. The results obtained for samples from six patients showed excellent agreement with those obtained by traditional microbiological methods.", "contents": "Rapid fluorimetric determination of 5-fluorocytosine in serum. A rapid fluorimetric procedure for the determination of the fungicide 5-fluorocytosine in serum is described. The method is high in precision (S.D. 1.6 mug/ml at 50 mug/ml) and specificity and can be performed in 60-90 minutes. The results obtained for samples from six patients showed excellent agreement with those obtained by traditional microbiological methods."}
{"id": "PMID:240519", "title": "A new method for the assay of aminoacylase: elaboration of a fixed-incubation method for routine measurements.", "content": "A simple method suitable for routine determinations of aminoacylase (EC 3.5.1.14) in serum and tissue homogenates is described. It is based on the formation of red charge-transfer complexes from p-benzoquinone and amino acids liberated by cleavage of acylamino acids. Optimal substrates are trifluoroacetyl-L-methionine and chloroacetyl-L-methionine, the first being rapidly hydrolyzed by pancreatic tissue, the latter by liver and kidney homogenates. Sera preferentially split the chloroacetyl compound. Optimal conditions for the assay of serum activity are: 18-20 mm9l/l substrate concentration, 50 mmol/l phosphate buffer pH 6.0, no additives.", "contents": "A new method for the assay of aminoacylase: elaboration of a fixed-incubation method for routine measurements. A simple method suitable for routine determinations of aminoacylase (EC 3.5.1.14) in serum and tissue homogenates is described. It is based on the formation of red charge-transfer complexes from p-benzoquinone and amino acids liberated by cleavage of acylamino acids. Optimal substrates are trifluoroacetyl-L-methionine and chloroacetyl-L-methionine, the first being rapidly hydrolyzed by pancreatic tissue, the latter by liver and kidney homogenates. Sera preferentially split the chloroacetyl compound. Optimal conditions for the assay of serum activity are: 18-20 mm9l/l substrate concentration, 50 mmol/l phosphate buffer pH 6.0, no additives."}
{"id": "PMID:240520", "title": "Isoelectrofocusing in acetate membrane: the method and application.", "content": "Acetate membrane as a new medium for isoelectrofocusing was used in this study. The acetate membrane was specially produced for isoelectrofocusing, and contains a surface active agent. The ampholine solution system and isoelectric condition for this purpose are described. Polymorphic traits as alpha1-antitrypsin in human serum and 6-phosphogluconate dehydrogenase (6-PGD) in human erythrocyte could be identified by this method. The isoelectric patterns and the isoelectric points of these proteins were demonstrated on the acetate membrane.", "contents": "Isoelectrofocusing in acetate membrane: the method and application. Acetate membrane as a new medium for isoelectrofocusing was used in this study. The acetate membrane was specially produced for isoelectrofocusing, and contains a surface active agent. The ampholine solution system and isoelectric condition for this purpose are described. Polymorphic traits as alpha1-antitrypsin in human serum and 6-phosphogluconate dehydrogenase (6-PGD) in human erythrocyte could be identified by this method. The isoelectric patterns and the isoelectric points of these proteins were demonstrated on the acetate membrane."}
{"id": "PMID:240521", "title": "Quantitative measurement of adenosine deaminase from human erythrocytes.", "content": "Methods for measuring enzymatic activity of adenosine deaminase from human erythrocytes were examined and compared with each other. Determination of ADA by the method in which adenosine is converted into inosine with uric acid as the final product by the action of nucleoside phosphorylase and xanthine oxidase appears to yield the most reliable results. In the recommended assay saponin is used for lysis of erythrocytes when testing adenosine deaminase activity in red blood cells. Storage of erythrocyte samples is optimal at +4 degrees C; storage at room temperature or at -20 degrees C leads to loss of adenosine deaminase activity.", "contents": "Quantitative measurement of adenosine deaminase from human erythrocytes. Methods for measuring enzymatic activity of adenosine deaminase from human erythrocytes were examined and compared with each other. Determination of ADA by the method in which adenosine is converted into inosine with uric acid as the final product by the action of nucleoside phosphorylase and xanthine oxidase appears to yield the most reliable results. In the recommended assay saponin is used for lysis of erythrocytes when testing adenosine deaminase activity in red blood cells. Storage of erythrocyte samples is optimal at +4 degrees C; storage at room temperature or at -20 degrees C leads to loss of adenosine deaminase activity."}
{"id": "PMID:240522", "title": "An immunochemical method for the selective measurement of two triglyceride lipases in human postheparin plasma.", "content": "A new method for the selective measurement of postheparin plasma lipoprotein lipase and hepatic lipase is described and validated. The activity of lipoprotein lipase is determined at 0.1 M NaCl after removal of hepatic lipase by specific antiserum, and the hepatic lipase is assayed in a medium containing 1.0 M NaCl but no additional serum. The optimal conditions for the determination of the two postheparin plasma triglyceride hydrolases were shown to be similar to those described for the purified enzymes. The new assay methods are simple, accurate and highly specific for the two lipase activities. VLDL and LDL do not interfere with the measurement, making the methods suitable for studies of patients with various hyperlipidemias. More than 90% of the total triglyceride hydrolase activity in postheparin plasma is precipitated with antisera raised against purified human postheparin plasma hepatic lipase and bovine milk lipoprotein lipase. The time and dose dependence of the two postheparin plasma lipase responses differ. For optimal activity of both enzymes, plasma taken 15 minutes after intravenous administration of 100 I.U./kg of heparin, should be used. The activity of postheparin plasma lipoprotein lipase and hepatic lipase in 12 young, healthy males is reported.", "contents": "An immunochemical method for the selective measurement of two triglyceride lipases in human postheparin plasma. A new method for the selective measurement of postheparin plasma lipoprotein lipase and hepatic lipase is described and validated. The activity of lipoprotein lipase is determined at 0.1 M NaCl after removal of hepatic lipase by specific antiserum, and the hepatic lipase is assayed in a medium containing 1.0 M NaCl but no additional serum. The optimal conditions for the determination of the two postheparin plasma triglyceride hydrolases were shown to be similar to those described for the purified enzymes. The new assay methods are simple, accurate and highly specific for the two lipase activities. VLDL and LDL do not interfere with the measurement, making the methods suitable for studies of patients with various hyperlipidemias. More than 90% of the total triglyceride hydrolase activity in postheparin plasma is precipitated with antisera raised against purified human postheparin plasma hepatic lipase and bovine milk lipoprotein lipase. The time and dose dependence of the two postheparin plasma lipase responses differ. For optimal activity of both enzymes, plasma taken 15 minutes after intravenous administration of 100 I.U./kg of heparin, should be used. The activity of postheparin plasma lipoprotein lipase and hepatic lipase in 12 young, healthy males is reported."}
{"id": "PMID:240523", "title": "A rapid method for the determination of deoxycytidylate deaminase activity in pregnancy serum.", "content": "A method is described for determining the activity of deoxycytidylate deaminase in serum. The ammonia liberated from deoxycytidine monophosphate has been specifically determined by enzymatic amination of alpha-ketoglutarate using glutamate dehydrogenase. The concurrent oxidation of NADH2 at 340 nm was proportional to the ammonia liberated from deoxycytidine monophosphate. Using the technique described, a result would be available to the clinician in under 4.5 h. The \"normal activity\" for deoxycytidine deaminase in normal male, female and pregnancy sera has been determined.", "contents": "A rapid method for the determination of deoxycytidylate deaminase activity in pregnancy serum. A method is described for determining the activity of deoxycytidylate deaminase in serum. The ammonia liberated from deoxycytidine monophosphate has been specifically determined by enzymatic amination of alpha-ketoglutarate using glutamate dehydrogenase. The concurrent oxidation of NADH2 at 340 nm was proportional to the ammonia liberated from deoxycytidine monophosphate. Using the technique described, a result would be available to the clinician in under 4.5 h. The \"normal activity\" for deoxycytidine deaminase in normal male, female and pregnancy sera has been determined."}
{"id": "PMID:240524", "title": "Studies on the carrier state in X-linked recessive (Duchenne) muscular dystrophy.", "content": "Observations in 12 normal women and 12 female carriers of X-linked recessive Duchenne muscular dystrophy (DMD), of whom 4 had symptoms and 8 had none, were compared between all 4 groups and with those in 2 DMD boys, one active and one crippled. Carrier symptoms were readily ascertained by systematic examination. Measurement of both lower legs in all 24 women showed neither calf enlargement nor asymmetry in carriers beyond normal variation. Two DMD carrier daughters were noted of the same DMD carrier mother but by different fathers. Whole body counting showed the biological half-life of previously administered 86Rb to be much reduced in DMD, but no differences were found between normal women and any group of carriers. The test is thus valueless for carrier detection, and reasons are given why it should be so. Simultaneous measurement of total body K+, with subsequent determination by isotope dilution of total body water as 3H2O space and extracellular water as NH4 82Br space, showed increased intracellular water and reduced intracellular K+ concentration in all carriers, as if due to osmotic causes, with actual loss of muscle mass and slight diminution of serum K+ in the 4 symptomatic carriers only. Because of diurnal and other variations, the means and standard deviations for six serum enzymes from six fortnightly assays in all subjects were used to measure precise individual status. Their coefficients of variation were abnormal only in symptomatic carriers and ambulant DMD, easily overtexed by even accustomed exertion. This is shown to support previous propositions on the pathogenesis of DMD and the escape of muscle cell content into the circulation.", "contents": "Studies on the carrier state in X-linked recessive (Duchenne) muscular dystrophy. Observations in 12 normal women and 12 female carriers of X-linked recessive Duchenne muscular dystrophy (DMD), of whom 4 had symptoms and 8 had none, were compared between all 4 groups and with those in 2 DMD boys, one active and one crippled. Carrier symptoms were readily ascertained by systematic examination. Measurement of both lower legs in all 24 women showed neither calf enlargement nor asymmetry in carriers beyond normal variation. Two DMD carrier daughters were noted of the same DMD carrier mother but by different fathers. Whole body counting showed the biological half-life of previously administered 86Rb to be much reduced in DMD, but no differences were found between normal women and any group of carriers. The test is thus valueless for carrier detection, and reasons are given why it should be so. Simultaneous measurement of total body K+, with subsequent determination by isotope dilution of total body water as 3H2O space and extracellular water as NH4 82Br space, showed increased intracellular water and reduced intracellular K+ concentration in all carriers, as if due to osmotic causes, with actual loss of muscle mass and slight diminution of serum K+ in the 4 symptomatic carriers only. Because of diurnal and other variations, the means and standard deviations for six serum enzymes from six fortnightly assays in all subjects were used to measure precise individual status. Their coefficients of variation were abnormal only in symptomatic carriers and ambulant DMD, easily overtexed by even accustomed exertion. This is shown to support previous propositions on the pathogenesis of DMD and the escape of muscle cell content into the circulation."}
{"id": "PMID:240525", "title": "Failure of adrenergic alpha and beta receptor blockade to elevate the TSH and prolactin response to TRH in hyperthyroidism.", "content": "The effects of adrenergic alpha and beta receptor blockade on the thyrotrophin and prolactin responses to TRH were studied in groups of hyperthyroid patients who received either oral propranolol and phenoxybenzamine or intravenous propranolol and rogitine. The flat TSH and prolactin responses to TRH in the untreated hyperthyroid patients were not altered by oral or intravenous adrenergic alpha and beta receptor blockade suggesting that catecholamines do not play a major role in the feedback suppression of TSH and prolactin in hyperthyroidism.", "contents": "Failure of adrenergic alpha and beta receptor blockade to elevate the TSH and prolactin response to TRH in hyperthyroidism. The effects of adrenergic alpha and beta receptor blockade on the thyrotrophin and prolactin responses to TRH were studied in groups of hyperthyroid patients who received either oral propranolol and phenoxybenzamine or intravenous propranolol and rogitine. The flat TSH and prolactin responses to TRH in the untreated hyperthyroid patients were not altered by oral or intravenous adrenergic alpha and beta receptor blockade suggesting that catecholamines do not play a major role in the feedback suppression of TSH and prolactin in hyperthyroidism."}
{"id": "PMID:240526", "title": "Optimum pH for nuclear sex identification using quinacrine.", "content": "Preparations of quinacrine stained interphase nuclei from buccal smears and hair root sheaths were mounted in MacIlvaine's buffer at various pH's in an attempt to obtain optimum differentiation of X- and Y-chromatin. Relatively high pH (5-8) was associated with intense nuclear fluorescence. Background nuclear fluorescence decreased with lower pH's (2-4), revealing distinct granules. X-chromatin is best differentiated against this decreased background, while positive identification of Y-chromatin is more certain in the absence of confusing granules. Hence optimum pH for X-chromatin screening in quinacrine stained preparations is approximately 3.0, that for Y-chromatin screening 5.5.", "contents": "Optimum pH for nuclear sex identification using quinacrine. Preparations of quinacrine stained interphase nuclei from buccal smears and hair root sheaths were mounted in MacIlvaine's buffer at various pH's in an attempt to obtain optimum differentiation of X- and Y-chromatin. Relatively high pH (5-8) was associated with intense nuclear fluorescence. Background nuclear fluorescence decreased with lower pH's (2-4), revealing distinct granules. X-chromatin is best differentiated against this decreased background, while positive identification of Y-chromatin is more certain in the absence of confusing granules. Hence optimum pH for X-chromatin screening in quinacrine stained preparations is approximately 3.0, that for Y-chromatin screening 5.5."}
{"id": "PMID:240527", "title": "A diploid-triploid human mosaic with cytogenetic evidence of double fertilization.", "content": "The karyotype 46,XX/69,XXY was found in a 13-year-old mentally subnormal patient with club feet, strabismus, eunuchoid habitus, small penis, midscrotal urethrovaginal opening, small descended left testis, and small undescended right testis; no ovarian tissue could be found at laparotomy. Triploid:diploid cell ratios were 60:40 and 4:96 in skin fibroblasts and curculating lymphocytes, respectively. In the triploid line, two of the no. 13 chromosomes had unusually large satellites and one of the no. 22 chromosomes had a brightly fluorescent zone on its short arms. The patient's father was heterozygous for both these autosomal markers; the mother carried neither marker. This, together with the single Y, indicated that the extra haploid set was derived from the father. Of several possible mechanisms, we favor the suggestion that double fertilization occurred; one sperm nucleus immediately fused with the egg nucleus producing the diploid line; the second sperm nucleus was incorporated later into one of the two cells resulting from the first division of the zygote, producing the triploid line.", "contents": "A diploid-triploid human mosaic with cytogenetic evidence of double fertilization. The karyotype 46,XX/69,XXY was found in a 13-year-old mentally subnormal patient with club feet, strabismus, eunuchoid habitus, small penis, midscrotal urethrovaginal opening, small descended left testis, and small undescended right testis; no ovarian tissue could be found at laparotomy. Triploid:diploid cell ratios were 60:40 and 4:96 in skin fibroblasts and curculating lymphocytes, respectively. In the triploid line, two of the no. 13 chromosomes had unusually large satellites and one of the no. 22 chromosomes had a brightly fluorescent zone on its short arms. The patient's father was heterozygous for both these autosomal markers; the mother carried neither marker. This, together with the single Y, indicated that the extra haploid set was derived from the father. Of several possible mechanisms, we favor the suggestion that double fertilization occurred; one sperm nucleus immediately fused with the egg nucleus producing the diploid line; the second sperm nucleus was incorporated later into one of the two cells resulting from the first division of the zygote, producing the triploid line."}
{"id": "PMID:240529", "title": "Effectiveness of hypnotic drugs with prolonged use: flurazepam and pentobarbital.", "content": "This study represents the first attempt to rigorously evaluate the effectiveness of hypnotic drugs under conditions of prolonged use. Flurazepam, 30 mg, and pentobarbital, 100 mg, were separately evaluated in identical 47-night sleep laboratory drug evaluation studies on insomniac subjects, which included 4 weeks of drug administration. Flurazepam was found to be effective in inducing and maintaining sleep over all treatment conditions. With long-term use, only a slight loss of effectiveness was suggested. Flurazepam also produced a moderate decrease in REM sleep and marked decrease in eye movement density and stage 4 sleep with short- and intermediate-term use. While the decreases in both REM sleep and eye movement density lessened with long-term use, stage 4 sleep remained markedly suppressed. No rebound was noted in any of these parameters after withdrawal. Pentobarbital was found to be effective in inducing and maintaining sleep only with short-term drug administration. This strongly suggests that it is of limited value for insomniac patients who require nightly medication beyond short-term use. Pentobarbital caused a minimal decrease in REM sleep with short- and intermediate-term administration, and slight rebound following withdrawal. Stages 3 and 4 sleep were decreased with short-term use and increased above baseline levels after withdrawal.", "contents": "Effectiveness of hypnotic drugs with prolonged use: flurazepam and pentobarbital. This study represents the first attempt to rigorously evaluate the effectiveness of hypnotic drugs under conditions of prolonged use. Flurazepam, 30 mg, and pentobarbital, 100 mg, were separately evaluated in identical 47-night sleep laboratory drug evaluation studies on insomniac subjects, which included 4 weeks of drug administration. Flurazepam was found to be effective in inducing and maintaining sleep over all treatment conditions. With long-term use, only a slight loss of effectiveness was suggested. Flurazepam also produced a moderate decrease in REM sleep and marked decrease in eye movement density and stage 4 sleep with short- and intermediate-term use. While the decreases in both REM sleep and eye movement density lessened with long-term use, stage 4 sleep remained markedly suppressed. No rebound was noted in any of these parameters after withdrawal. Pentobarbital was found to be effective in inducing and maintaining sleep only with short-term drug administration. This strongly suggests that it is of limited value for insomniac patients who require nightly medication beyond short-term use. Pentobarbital caused a minimal decrease in REM sleep with short- and intermediate-term administration, and slight rebound following withdrawal. Stages 3 and 4 sleep were decreased with short-term use and increased above baseline levels after withdrawal."}
{"id": "PMID:240530", "title": "Studies on the nature of complexes formed by copper with human alimentary secretions and their influence on copper absorption in the rat.", "content": "1. Human gastrointestinal secretions formed soluble copper complexes when labelled in vitro with 64Cu. 2. Copper-binding substances of low molecular weight were demonstrated in the saliva, gastric juice and secretin-stimulated duodenal aspirate of nomal subjects by dialysis and gel-chromatography studies. 3. The nature of the copper complexes formed by secretions obtained from patients with Wilson's disease was similar to that oc complexes formed by secretions of normal subjects. 4. Bile contained a copper-binding fraction of high molecular weight which was more concentrated in gall-bladder than hepatic bile. Between pH 5 and pH 8, this component had a greater binding affinity EDTA at a concentration of 10 mmol/1. 5. Absorption of 64Cu from 64Cu-labelled saliva, gastric juice or L-histidine solution (100 mmol/1) administered intraduodenally into groups of rats was similar to that observed in a control series given [Cu]cupric acetate in sodium chloride solution. In contrast, the absorption of 64Cu from labelled hepatic and gall-bladder bile was significantly reduced. 6. The results suggest that dietary copper forms soluble complexes with the alimentary secretions and that these complexes influence absorption of the metal according to their molecular size. The net uptake of ingested copper from the gut lumen ms, low-molecular-weight ligands in the alimentary secretions and a macromolecular copper-binding complex of bile.", "contents": "Studies on the nature of complexes formed by copper with human alimentary secretions and their influence on copper absorption in the rat. 1. Human gastrointestinal secretions formed soluble copper complexes when labelled in vitro with 64Cu. 2. Copper-binding substances of low molecular weight were demonstrated in the saliva, gastric juice and secretin-stimulated duodenal aspirate of nomal subjects by dialysis and gel-chromatography studies. 3. The nature of the copper complexes formed by secretions obtained from patients with Wilson's disease was similar to that oc complexes formed by secretions of normal subjects. 4. Bile contained a copper-binding fraction of high molecular weight which was more concentrated in gall-bladder than hepatic bile. Between pH 5 and pH 8, this component had a greater binding affinity EDTA at a concentration of 10 mmol/1. 5. Absorption of 64Cu from 64Cu-labelled saliva, gastric juice or L-histidine solution (100 mmol/1) administered intraduodenally into groups of rats was similar to that observed in a control series given [Cu]cupric acetate in sodium chloride solution. In contrast, the absorption of 64Cu from labelled hepatic and gall-bladder bile was significantly reduced. 6. The results suggest that dietary copper forms soluble complexes with the alimentary secretions and that these complexes influence absorption of the metal according to their molecular size. The net uptake of ingested copper from the gut lumen ms, low-molecular-weight ligands in the alimentary secretions and a macromolecular copper-binding complex of bile."}
{"id": "PMID:240644", "title": "Effect of ionic strength and pH on the properties of purified bovine testicular hyaluronidase.", "content": "Studies on the effect of pH and ionic strength upon the activity of purified bovine testicular hyaluronidase have shown that the pH optimum for the hydrolysis of hyaluronic acid occurs at 5.2 in the presence of, and at 6.0 in the absence of NaCl. Hydrolytic activity towards various mucopolysaccharide and hyaluronate octasaccharide substrates was dependent upon the presence of strong electrolyte (LiCl, NaCl, KCl, CsCl, NaNO3 and Na2SO4), maximum activity being obtained at electrolyte strengths of 0.2. Identical weights of sulphated and unsulphated mucopolysaccharides were hydrolysed at similar rates under optimal conditions, except that double chains of chondroitin 4-sulphate were hydrolysed at twice the rate of the other polysaccharides. Hydrolytic activity towards hyaluronate hexasaccharide was favoured at pH values below 5.2 whereas transglycosylation activity was favoured at higher pH. Hyaluronate tetrasaccharide was neither a substrate for the hydrolytic or transglycosylation activity, nor was it an inhibitor of the enzymic hydrolysis of hyaluronic acid. No conformational change in hyaluronic acid was detected by CD-spectroscopy in the presence of varying concentrations of salt and the collective results suggest that the salt effect is exerted on the enzyme rather than on the substrate.", "contents": "Effect of ionic strength and pH on the properties of purified bovine testicular hyaluronidase. Studies on the effect of pH and ionic strength upon the activity of purified bovine testicular hyaluronidase have shown that the pH optimum for the hydrolysis of hyaluronic acid occurs at 5.2 in the presence of, and at 6.0 in the absence of NaCl. Hydrolytic activity towards various mucopolysaccharide and hyaluronate octasaccharide substrates was dependent upon the presence of strong electrolyte (LiCl, NaCl, KCl, CsCl, NaNO3 and Na2SO4), maximum activity being obtained at electrolyte strengths of 0.2. Identical weights of sulphated and unsulphated mucopolysaccharides were hydrolysed at similar rates under optimal conditions, except that double chains of chondroitin 4-sulphate were hydrolysed at twice the rate of the other polysaccharides. Hydrolytic activity towards hyaluronate hexasaccharide was favoured at pH values below 5.2 whereas transglycosylation activity was favoured at higher pH. Hyaluronate tetrasaccharide was neither a substrate for the hydrolytic or transglycosylation activity, nor was it an inhibitor of the enzymic hydrolysis of hyaluronic acid. No conformational change in hyaluronic acid was detected by CD-spectroscopy in the presence of varying concentrations of salt and the collective results suggest that the salt effect is exerted on the enzyme rather than on the substrate."}
{"id": "PMID:240645", "title": "Lysyl oxidase deficiency in Ehlers-Danlos syndrome type V.", "content": "Two maternal cousins affected by the X-linked form of Ehlers-Danlos syndrome have been observed. Both had congenital heart disease, \"floppy valve syndrome\", hernias, short stature, stretchable skin and moderate joint hypermobility. Both excreted normal amounts of urinary glycosaminoglycans, almost entirely represented by dermatan sulfate, whose degradation appeared to be inadequate. They also excreted large amounts of hydroxylysine glycosides and L-valyl-proline, considered to be products of degradation of collagen and elastin, respectively. Cultured skin fibroblasts of the propositus synthesized excessively soluble collagen and had a low lysyl oxidase activity. These findings suggest that the increased degradation of structural proteins may be secondary to the defective cross-linking processes caused by the enzymic defect. Addition of (+) catechin, a flavonoid, to the propositus's cultured fibroblasts decreased the abnormal solubility of their collagen.", "contents": "Lysyl oxidase deficiency in Ehlers-Danlos syndrome type V. Two maternal cousins affected by the X-linked form of Ehlers-Danlos syndrome have been observed. Both had congenital heart disease, \"floppy valve syndrome\", hernias, short stature, stretchable skin and moderate joint hypermobility. Both excreted normal amounts of urinary glycosaminoglycans, almost entirely represented by dermatan sulfate, whose degradation appeared to be inadequate. They also excreted large amounts of hydroxylysine glycosides and L-valyl-proline, considered to be products of degradation of collagen and elastin, respectively. Cultured skin fibroblasts of the propositus synthesized excessively soluble collagen and had a low lysyl oxidase activity. These findings suggest that the increased degradation of structural proteins may be secondary to the defective cross-linking processes caused by the enzymic defect. Addition of (+) catechin, a flavonoid, to the propositus's cultured fibroblasts decreased the abnormal solubility of their collagen."}
{"id": "PMID:240646", "title": "Concerted action of beta-glucuronidase and beta-acetylglucosaminidase on hyaluronodextrins.", "content": "A kinetic analysis of the stepwise alternating action of beta-glucuronidase and beta-acetylglucosaminidase on oligosaccharides and dextrins derived from hyaluronic acid was undertaken, for better definition of the contribution of this process to hyaluronate catabolism. Production of monosaccharide from larger dextrins by action of either enzyme is powerfully inhibited by electrolyts. In the study, as in mammalian tissues, beta-glucuronidase is present in excess so that the concentration of beta-acetylglucosaminidase is rate controlling in the action on dextrin substrates. For this action, Vmax shows limited variation with ionic strength or molecular weight of substrate. At ionic strength 0.03, but not 0.18, Km decreases some 100-fold for increase of molecular weight from 2,000 to 15,000. It is specifically this decrease in Km that accounts for the prominent electrolyte inhibition observed with larger dextrins. The extremely low values of Km are attributed to multiple ionic enzyme-substrate interactions at sites remote from the catalytic center. The previously reported stimulation by electrolyte of the action of beta-glucuronidase and beta-acetylglucosaminidase on aryl glycosides, studied briefly, is apparently unrelated to the electrolyte effects seen with dextrins. The catabolic contribution of beta-glucuronidase and beta-acetylglucosaminidase appears to be restricted to hydrolysis of the smaller oligosaccharides produced by action of hyaluronidase, since, for any reasonable assumptions regarding cellular environment, the extent of their action on polymeric hyaluronate or larger dextrins must be limited.", "contents": "Concerted action of beta-glucuronidase and beta-acetylglucosaminidase on hyaluronodextrins. A kinetic analysis of the stepwise alternating action of beta-glucuronidase and beta-acetylglucosaminidase on oligosaccharides and dextrins derived from hyaluronic acid was undertaken, for better definition of the contribution of this process to hyaluronate catabolism. Production of monosaccharide from larger dextrins by action of either enzyme is powerfully inhibited by electrolyts. In the study, as in mammalian tissues, beta-glucuronidase is present in excess so that the concentration of beta-acetylglucosaminidase is rate controlling in the action on dextrin substrates. For this action, Vmax shows limited variation with ionic strength or molecular weight of substrate. At ionic strength 0.03, but not 0.18, Km decreases some 100-fold for increase of molecular weight from 2,000 to 15,000. It is specifically this decrease in Km that accounts for the prominent electrolyte inhibition observed with larger dextrins. The extremely low values of Km are attributed to multiple ionic enzyme-substrate interactions at sites remote from the catalytic center. The previously reported stimulation by electrolyte of the action of beta-glucuronidase and beta-acetylglucosaminidase on aryl glycosides, studied briefly, is apparently unrelated to the electrolyte effects seen with dextrins. The catabolic contribution of beta-glucuronidase and beta-acetylglucosaminidase appears to be restricted to hydrolysis of the smaller oligosaccharides produced by action of hyaluronidase, since, for any reasonable assumptions regarding cellular environment, the extent of their action on polymeric hyaluronate or larger dextrins must be limited."}
{"id": "PMID:240647", "title": "Denaturation of collagen fibers in NaI, NaCl and water of different pH values as studied by differential scanning calorimetric measurements.", "content": "Microcalorimetric measurements of rat tail tendon collagen in different aqueous media show the following behavior of denaturation temperature (Td) and of denaturation enthalpy (deltaHd): H+ and OH- ions lower Td significantly beyond pH 4...11. Addition of salts (0.15 M) generally lowers Td in the range between pH 5 and 10, I- being more effective than Cl- at pH greater than i.p. However, in the region of pH less than i.p., I- raises Td to values above those of Cl- and even those of water. The value of deltaHd was found to be insensitive to pH over the pH range of 4...11. Hence the lowering of Td is assumed firstly to be due to a (ionic) disorganization of the water contacting the polypeptide chains and secondly to their mutual electrostatic repulsion. The appearance of deltaHd is thought mainly to be due to a rupture of interchain bonds.", "contents": "Denaturation of collagen fibers in NaI, NaCl and water of different pH values as studied by differential scanning calorimetric measurements. Microcalorimetric measurements of rat tail tendon collagen in different aqueous media show the following behavior of denaturation temperature (Td) and of denaturation enthalpy (deltaHd): H+ and OH- ions lower Td significantly beyond pH 4...11. Addition of salts (0.15 M) generally lowers Td in the range between pH 5 and 10, I- being more effective than Cl- at pH greater than i.p. However, in the region of pH less than i.p., I- raises Td to values above those of Cl- and even those of water. The value of deltaHd was found to be insensitive to pH over the pH range of 4...11. Hence the lowering of Td is assumed firstly to be due to a (ionic) disorganization of the water contacting the polypeptide chains and secondly to their mutual electrostatic repulsion. The appearance of deltaHd is thought mainly to be due to a rupture of interchain bonds."}
{"id": "PMID:240652", "title": "Effects of chronic administration of bromazepam on its blood level profile and on the hepatic microsomal drug-metabolizing enzymes in the rat.", "content": "After oral administration of bromazepam, 50 mg/kg/day for 14-28 days to rats, the rate of elimination of the unchanged drug from the blood increased by 20-40%, as determined from the half-lives of the blood decay curves during the first 4 hr after administration of an oral or intravenous test dose of bromazepam. During the chronic administration, the liver weight increased 30-40%, with concomitant enlargement of the liver. The hepatomegaly was associated with elevation of microsomal drug-metabolizing enzyme activities, including that responsible for the oxidation of bromazepam itself. Spectral characteristics of the isolated microsomes indicated that the manner by which bromazepam caused the elevation (induction) of the enzyme activities was of the \"phenobarbital type\" rather than the \"methylcholanthrene type.\" Since certain steps of bromazepam metabolism take place in the liver, it appears reasonable to assume that the increase in the elimination rate found after chronic administration may depend upon the enhanced drug-metabolizing activities in the liver. The hepatomegaly and the associated elevation of enzyme activities returned to the normal states within 7 days after withdrawal of the drug. Neither the increase in the elimination rate nor the enzyme induction was observed with doses lower than 5 mg/kg.", "contents": "Effects of chronic administration of bromazepam on its blood level profile and on the hepatic microsomal drug-metabolizing enzymes in the rat. After oral administration of bromazepam, 50 mg/kg/day for 14-28 days to rats, the rate of elimination of the unchanged drug from the blood increased by 20-40%, as determined from the half-lives of the blood decay curves during the first 4 hr after administration of an oral or intravenous test dose of bromazepam. During the chronic administration, the liver weight increased 30-40%, with concomitant enlargement of the liver. The hepatomegaly was associated with elevation of microsomal drug-metabolizing enzyme activities, including that responsible for the oxidation of bromazepam itself. Spectral characteristics of the isolated microsomes indicated that the manner by which bromazepam caused the elevation (induction) of the enzyme activities was of the \"phenobarbital type\" rather than the \"methylcholanthrene type.\" Since certain steps of bromazepam metabolism take place in the liver, it appears reasonable to assume that the increase in the elimination rate found after chronic administration may depend upon the enhanced drug-metabolizing activities in the liver. The hepatomegaly and the associated elevation of enzyme activities returned to the normal states within 7 days after withdrawal of the drug. Neither the increase in the elimination rate nor the enzyme induction was observed with doses lower than 5 mg/kg."}
{"id": "PMID:240653", "title": "Inherent specificities of purified cytochromes P-450 and P-448 toward biphenyl hydroxylation and ethoxyresorufin deethylation.", "content": "Liver microsomes from 3-methylcholanthrene-pretreated Long-Evans rats catalyzed the 2- and the 4-hydroxylation of biphenyl and the O-deethylation of ethoxyresorufin, sustained by either NADPH or cumene hydroperoxide. In contrast, the liver microsomes from corn oil- or phenobarbital-pretreated rats catalyzed the NADPH- or cumene hydroperoxide-sustained 4-hydroxylation of biphenyl, but the rates of 2-hydroxylation or ethoxyresorufin deethylation were negligible. A monooxygenase system reconstituted with partially purified NADPH-cytochrome  c reductase and cytochrome P-448 catalyzed NADPH-supported biphenyl 2- and 4-hydroxylation and ethoxyresorufin deethylation. A monooxygenase system reconstituted with the reductase and cytochrome P-450 catalyzed NADPH-supported biphenyl 4-hydroxylation but exhibited negligible 2-hydroxylation or ethoxyresorufin deethylation activites. Solubilized cytochrome P-448 catalyzed biphenyl 2- and 4-hydroxylation and ethoxyresorufin deethylation sustained by cumene hydroperoxide in the absence of both NADPH and NADPH-cytochrome c reductase, whereas solubilized cytochrome P-450, under the same conditions, catalyzed only biphenyl 4-hydroxylation. It is concluded that the patterns of biphenyl hydroxylation and ethoxyresorufin deethylation observed with live- microsomes from untreated or inducer-treated rats are due largely to the inherent enzymic specificities of their cytochromes P-450 and P-448.", "contents": "Inherent specificities of purified cytochromes P-450 and P-448 toward biphenyl hydroxylation and ethoxyresorufin deethylation. Liver microsomes from 3-methylcholanthrene-pretreated Long-Evans rats catalyzed the 2- and the 4-hydroxylation of biphenyl and the O-deethylation of ethoxyresorufin, sustained by either NADPH or cumene hydroperoxide. In contrast, the liver microsomes from corn oil- or phenobarbital-pretreated rats catalyzed the NADPH- or cumene hydroperoxide-sustained 4-hydroxylation of biphenyl, but the rates of 2-hydroxylation or ethoxyresorufin deethylation were negligible. A monooxygenase system reconstituted with partially purified NADPH-cytochrome  c reductase and cytochrome P-448 catalyzed NADPH-supported biphenyl 2- and 4-hydroxylation and ethoxyresorufin deethylation. A monooxygenase system reconstituted with the reductase and cytochrome P-450 catalyzed NADPH-supported biphenyl 4-hydroxylation but exhibited negligible 2-hydroxylation or ethoxyresorufin deethylation activites. Solubilized cytochrome P-448 catalyzed biphenyl 2- and 4-hydroxylation and ethoxyresorufin deethylation sustained by cumene hydroperoxide in the absence of both NADPH and NADPH-cytochrome c reductase, whereas solubilized cytochrome P-450, under the same conditions, catalyzed only biphenyl 4-hydroxylation. It is concluded that the patterns of biphenyl hydroxylation and ethoxyresorufin deethylation observed with live- microsomes from untreated or inducer-treated rats are due largely to the inherent enzymic specificities of their cytochromes P-450 and P-448."}
{"id": "PMID:240654", "title": "Effect of pregnancy or treatment with cetain steroids on N,N-dimethylaniline demethylation and N-oxidation by rabbit liver or lung microsomes.", "content": "Rates of lung microsomal dimethylaniline (DMA) demethylation and N-oxidation as well as cytochrome P-450 concentrations from 20- and 28-day pregnant rabbits were observed to be as much as 2 times the values measured in lung microsomes from adult female nonpregnant rabbits. These increases were not seen in lung microsomes from 10-day pregnant rabbits, and only small increases were observed in lung microsomes from 15-day pregnant rabbits. In contrast, no differences were seen in hepatic microsomal DMA demethylase or N-oxidase activities at any stage of pregnancy. An attempt was made to correlate high plasma concentrations of steroids during pregnancy with the elevated enzyme activities observed in lung microsomes. Adult nonpregnant rabbits were treated with a variety of steroids, the concentrations of which have been shown to increase in plasma during late pregnancy. No effect on lung or liver microsomal DMA metabolism was observed when rabbits were treated with testosterone propionate. However, after animal pretreatment with the glucocorticoids, dexamethasone and hydrocortisone, there was a 40-60% increase in DMA demethylase and N-oxidase activities in liver and lung microsomes from adult male and nonpregnant female rabbits. Following pretreatment of adult female nonpregnant rabbits with the mineralocorticoid, deoxycorticosterone, an increase of 50% in rats of microsomal DMA metabolism in lung but not in liver was observed.", "contents": "Effect of pregnancy or treatment with cetain steroids on N,N-dimethylaniline demethylation and N-oxidation by rabbit liver or lung microsomes. Rates of lung microsomal dimethylaniline (DMA) demethylation and N-oxidation as well as cytochrome P-450 concentrations from 20- and 28-day pregnant rabbits were observed to be as much as 2 times the values measured in lung microsomes from adult female nonpregnant rabbits. These increases were not seen in lung microsomes from 10-day pregnant rabbits, and only small increases were observed in lung microsomes from 15-day pregnant rabbits. In contrast, no differences were seen in hepatic microsomal DMA demethylase or N-oxidase activities at any stage of pregnancy. An attempt was made to correlate high plasma concentrations of steroids during pregnancy with the elevated enzyme activities observed in lung microsomes. Adult nonpregnant rabbits were treated with a variety of steroids, the concentrations of which have been shown to increase in plasma during late pregnancy. No effect on lung or liver microsomal DMA metabolism was observed when rabbits were treated with testosterone propionate. However, after animal pretreatment with the glucocorticoids, dexamethasone and hydrocortisone, there was a 40-60% increase in DMA demethylase and N-oxidase activities in liver and lung microsomes from adult male and nonpregnant female rabbits. Following pretreatment of adult female nonpregnant rabbits with the mineralocorticoid, deoxycorticosterone, an increase of 50% in rats of microsomal DMA metabolism in lung but not in liver was observed."}
{"id": "PMID:240657", "title": "Sequestration of neostigmine and metabolites by perfused rat liver.", "content": "Isolated rat livers were perfused with 0.9 to 18 mumol of 14C-neostigmine (NEO) or 14C-(3-hydroxyphenyl)trimethylammonium (HPTMA). Within 30 min. 30-90% of the administered doses were sequestered by the liver. The initial extraction rate was equivalent to about 15% of the perfusion rate. There was no evidence for saturation of the rate or the extent of sequestration of NEO or HPTMA over the dosage range examined. The amount of radioactivity in the liver remained relatively constant for several hours while NEO was converted to HPTMA and its glucuronide (G-HPTMA), plus small amounts of other metabolites. HPTMA rapidly appeared in the perfusate, but there was about an hour lag in the appearance of G-HPTMA. The concentrations of NEO and major metabolites were generally higher in the liver than in the perfusate.", "contents": "Sequestration of neostigmine and metabolites by perfused rat liver. Isolated rat livers were perfused with 0.9 to 18 mumol of 14C-neostigmine (NEO) or 14C-(3-hydroxyphenyl)trimethylammonium (HPTMA). Within 30 min. 30-90% of the administered doses were sequestered by the liver. The initial extraction rate was equivalent to about 15% of the perfusion rate. There was no evidence for saturation of the rate or the extent of sequestration of NEO or HPTMA over the dosage range examined. The amount of radioactivity in the liver remained relatively constant for several hours while NEO was converted to HPTMA and its glucuronide (G-HPTMA), plus small amounts of other metabolites. HPTMA rapidly appeared in the perfusate, but there was about an hour lag in the appearance of G-HPTMA. The concentrations of NEO and major metabolites were generally higher in the liver than in the perfusate."}
{"id": "PMID:240658", "title": "Metabolism of tolmetin in rat, monkey, and man.", "content": "5-p-Carboxybenzoyl-1-methylpyrrole-2-acetic acid has been identified in the rat, monkey, and man as the major urinary metabolite of tolmetin, a new nonsteroidal anti-inflammatory agent. Conjugation of tolmetin, a major mode of disposition in man and monkey, was not observed in the rat.", "contents": "Metabolism of tolmetin in rat, monkey, and man. 5-p-Carboxybenzoyl-1-methylpyrrole-2-acetic acid has been identified in the rat, monkey, and man as the major urinary metabolite of tolmetin, a new nonsteroidal anti-inflammatory agent. Conjugation of tolmetin, a major mode of disposition in man and monkey, was not observed in the rat."}
{"id": "PMID:240655", "title": "Comparison of in vitro drug metabolism by lung, liver, and kidney of several common laboratory species.", "content": "Comparative studies of in vitro drug metabolism by hepatic and extrahepatic tissues have been complicated by the use of a single experimental tissue, few animal species, and variable experimental conditions. In an attempt to minimize these complications, liver, lung and kidney from rat, mouse, rabbit, hamster, and guinea pig were assayed for standard microsomal and soluble fraction enzymes involved in drug biotransformation. For all species, liver was the most active organ. Kidney and lung activities were usually 15%-40% of those found in liver, with kidney slightly more active than lung. No single species demonstrated total superiority in its drug-metabolizing ability, although hamster showed a large number of instances of greatest activity. The rat was a surprisingly poor representative of drug-metabolizing ability; it was superior to the other four species in less than 25% of the instances studied. All species appeared to N-demethylate aminopyrine equally except for high pulmonary and nearly absent renal activities in rabbit and high hepatic activity in hamster. Rat had the lowest level of cytochrome P-450 and low activity of NADPH-cytochrome c reductase. UDP-glucuronyltransferase activity toward the acceptors p-nitrophenol and o-aminophenol was higher in hamster and rabbit than other species. Guinea pig appeared to have the most active soluble fraction enzymes. Mouse lung and kidney had glutathione S-aryltransferase activities 10-fold greater than any other species and comparable to liver activity from rabbit and hamster.", "contents": "Comparison of in vitro drug metabolism by lung, liver, and kidney of several common laboratory species. Comparative studies of in vitro drug metabolism by hepatic and extrahepatic tissues have been complicated by the use of a single experimental tissue, few animal species, and variable experimental conditions. In an attempt to minimize these complications, liver, lung and kidney from rat, mouse, rabbit, hamster, and guinea pig were assayed for standard microsomal and soluble fraction enzymes involved in drug biotransformation. For all species, liver was the most active organ. Kidney and lung activities were usually 15%-40% of those found in liver, with kidney slightly more active than lung. No single species demonstrated total superiority in its drug-metabolizing ability, although hamster showed a large number of instances of greatest activity. The rat was a surprisingly poor representative of drug-metabolizing ability; it was superior to the other four species in less than 25% of the instances studied. All species appeared to N-demethylate aminopyrine equally except for high pulmonary and nearly absent renal activities in rabbit and high hepatic activity in hamster. Rat had the lowest level of cytochrome P-450 and low activity of NADPH-cytochrome c reductase. UDP-glucuronyltransferase activity toward the acceptors p-nitrophenol and o-aminophenol was higher in hamster and rabbit than other species. Guinea pig appeared to have the most active soluble fraction enzymes. Mouse lung and kidney had glutathione S-aryltransferase activities 10-fold greater than any other species and comparable to liver activity from rabbit and hamster."}
{"id": "PMID:240659", "title": "Metabolism of methaqualone by the epoxide-diol pathway in man and the rat.", "content": "The metabolism of methaqualone (2-methyl-3-o-tolyl-4(3H)-quinazolinone) has been studied in man and the rat using gas phase analytical methods. Seven new metabolites formed by the epoxide-diol pathway were detected in human urine after methaqualone administration. Five of these compounds were characterized as dihydrodiols and two as hydroxydihydrodiols. The seven dihydrodiol metabolites were present in the nonhydrolyzed fraction isolated from urine. After intraperitoneal administration of methaqualone to the rat (40 mg/kg) the major monohydroxyl metabolites of the drug in hydrolyzed urine were identified as 2-methyl-3-(2'-hydroxymethylphenyl)-4(3H)-quinazolinone (I) and 2-hydroxymethyl-3-o-tolyl-4(3H)-quinazolinone (II). Two dihydroxyl metabolites were also present, but only trace amounts of a dihydrodiol were detected. The major monohydroxyl metabolites of methaqualone detected in human urine after enzymic hydrolysis were I, II, 2-methyl-3-(3'-hydroxy-2'-methylphenyl)-4(3H)-quinazolinone (III), and 2-methyl-3-(4'-hydroxy-2'-methylphenyl)-4(3H)-quinazolinone (IV). Hydroxylation of the tolyl moiety of methaqualone probably occurs by way of an epoxide intermediate. The phenols, III and IV, may be formed from an epoxide or from the dihydrodiol(s) by enzymic or nonenzymic reactions. The results obtained suggest that epoxidation of methaqualone represents a major pathway of metabolism in the human.", "contents": "Metabolism of methaqualone by the epoxide-diol pathway in man and the rat. The metabolism of methaqualone (2-methyl-3-o-tolyl-4(3H)-quinazolinone) has been studied in man and the rat using gas phase analytical methods. Seven new metabolites formed by the epoxide-diol pathway were detected in human urine after methaqualone administration. Five of these compounds were characterized as dihydrodiols and two as hydroxydihydrodiols. The seven dihydrodiol metabolites were present in the nonhydrolyzed fraction isolated from urine. After intraperitoneal administration of methaqualone to the rat (40 mg/kg) the major monohydroxyl metabolites of the drug in hydrolyzed urine were identified as 2-methyl-3-(2'-hydroxymethylphenyl)-4(3H)-quinazolinone (I) and 2-hydroxymethyl-3-o-tolyl-4(3H)-quinazolinone (II). Two dihydroxyl metabolites were also present, but only trace amounts of a dihydrodiol were detected. The major monohydroxyl metabolites of methaqualone detected in human urine after enzymic hydrolysis were I, II, 2-methyl-3-(3'-hydroxy-2'-methylphenyl)-4(3H)-quinazolinone (III), and 2-methyl-3-(4'-hydroxy-2'-methylphenyl)-4(3H)-quinazolinone (IV). Hydroxylation of the tolyl moiety of methaqualone probably occurs by way of an epoxide intermediate. The phenols, III and IV, may be formed from an epoxide or from the dihydrodiol(s) by enzymic or nonenzymic reactions. The results obtained suggest that epoxidation of methaqualone represents a major pathway of metabolism in the human."}
{"id": "PMID:240656", "title": "Interaction of aromatic nitro compounds with reduced hepatic microsomal cytochrome P-450.", "content": "Aromatic nitro compounds interact with sodium dithionite-reduced microsomes to generate difference spectra characterized by a maximum at 400 nm and minima at 440 and 528 nm. Spectral binding constants of approximately 1 mM were calculated for ferrohemochromes in which nitrobenzene, p-nitrobenzoate, 2-nitrofluorene, and 2-nitronaphthalene served as ligands. Nitro binding affinity was increased approximately 3-fold by pretreatment of animals with phenobarbital (KS congruent to 0.3 mM). The interaction of nitro compounds with reduced microsomes from 3-methylcholanthrene-pretreated animals, however, failed to give discernable difference spectra. There is apparent mutual inhibition of binding of carbon monoxide, metyrapone, and nitro compounds with reduced cytochrome P-450, since addition of metyrapone or carbon monoxide to reference and sample cuvettes does not alter qualitative aspects of the nitro binding spectra, but only its magnitude. From the relative KS values, it is concluded that metyrapone and carbon monoxide interact with reduced cytochrome P-450 more tenaciously than nitro compounds.", "contents": "Interaction of aromatic nitro compounds with reduced hepatic microsomal cytochrome P-450. Aromatic nitro compounds interact with sodium dithionite-reduced microsomes to generate difference spectra characterized by a maximum at 400 nm and minima at 440 and 528 nm. Spectral binding constants of approximately 1 mM were calculated for ferrohemochromes in which nitrobenzene, p-nitrobenzoate, 2-nitrofluorene, and 2-nitronaphthalene served as ligands. Nitro binding affinity was increased approximately 3-fold by pretreatment of animals with phenobarbital (KS congruent to 0.3 mM). The interaction of nitro compounds with reduced microsomes from 3-methylcholanthrene-pretreated animals, however, failed to give discernable difference spectra. There is apparent mutual inhibition of binding of carbon monoxide, metyrapone, and nitro compounds with reduced cytochrome P-450, since addition of metyrapone or carbon monoxide to reference and sample cuvettes does not alter qualitative aspects of the nitro binding spectra, but only its magnitude. From the relative KS values, it is concluded that metyrapone and carbon monoxide interact with reduced cytochrome P-450 more tenaciously than nitro compounds."}
{"id": "PMID:240665", "title": "[The significance of lipoprotein X in the diagnosis of obstructive jaundice: comparison with other biochemical tests (author's transl)].", "content": "The reliability of lipoprotein-X demonstration in the diagnosis of obstructive jaundice was tested in 660 patients (1105 samples) and compared with other biochemical studies. Groups of 100 patients each with morphologically proven liver or biliary-tract disease were analyzed in order to determine the frequency with which the demonstration of lipoprotein X and biliary stasis coincided. There was no direct connection between hepatitis B antigen and lipoprotein X. Total cholesterol concentration provided no help in the differential diagnosis of jaundice, although in a series of cases with and without obstruction the mean concentrations differed significantly. Intra- and extrahepatic causes of jaundice and their aetiology could not be clarified merely by demonstrating the presence or absence of lipoprotein X. Nonetheless, it is a simple and safe method for proving biliary stasis.", "contents": "[The significance of lipoprotein X in the diagnosis of obstructive jaundice: comparison with other biochemical tests (author's transl)]. The reliability of lipoprotein-X demonstration in the diagnosis of obstructive jaundice was tested in 660 patients (1105 samples) and compared with other biochemical studies. Groups of 100 patients each with morphologically proven liver or biliary-tract disease were analyzed in order to determine the frequency with which the demonstration of lipoprotein X and biliary stasis coincided. There was no direct connection between hepatitis B antigen and lipoprotein X. Total cholesterol concentration provided no help in the differential diagnosis of jaundice, although in a series of cases with and without obstruction the mean concentrations differed significantly. Intra- and extrahepatic causes of jaundice and their aetiology could not be clarified merely by demonstrating the presence or absence of lipoprotein X. Nonetheless, it is a simple and safe method for proving biliary stasis."}
{"id": "PMID:240662", "title": "Pharmacologic studies of cyclocytidine and arabinosylcytosine in dogs.", "content": "Cyclocytidine (cyclo-C) and arabinosylcytosine (ara-C) were compared as to distribution and metabolism in dogs after administration by the intravenous, subcutaneous, intramuscular, and oral routes. After cyclo-C, two metabolites were found in the plasma and urine--a hydrolytic product, ara-C, and its deaminated product, arabinosyluracil (ara-U). The urinary excretion of cyclo-C is rapid; Five hours after parenteral administration, 60% of the given drug is excreted; 45% as cyclo-C, 10% as ara-C, and about 5% as ara-U. In contrast, after similar injections of ara-C, 45% of the drug is excreted; 33% as ara-C and 12% as ara-U. When compared with those in human and mouse tissues, the deoxycytidine deaminase levels in dog tissues are extremely low. This agrees with the finding of low ara-U levels in dog plasma and urine after administering cyclo-C or ara-C. Regardless whether cyclo-C or ara-C is injected, the plasma decay curve of the resultant ara-C is biphasic, with calculated half-lives of 40 min and 2-2.5 hr. However, if ara-C is given, the plasma ara-C peak level is higher. Higher ara-C levels are also maintained throughout the measured 5 hr. There are no differences in pharmacologic disposition after iv, sc, or im administration of ara-C. This is also true for cyclo-C. These findings suggest that for both drugs, the above routes of administration may be equally effective. Neither cyclo-C nor ara-C is well absorbed after oral administration, and the drug concentration in the plasma is too low to be measurable. Whether the dog is fasted overnight or fed, the drug is excreted slowly. In 5 hr. no more than 3% is excreted, and by 12 hr. only 10% is excreted.", "contents": "Pharmacologic studies of cyclocytidine and arabinosylcytosine in dogs. Cyclocytidine (cyclo-C) and arabinosylcytosine (ara-C) were compared as to distribution and metabolism in dogs after administration by the intravenous, subcutaneous, intramuscular, and oral routes. After cyclo-C, two metabolites were found in the plasma and urine--a hydrolytic product, ara-C, and its deaminated product, arabinosyluracil (ara-U). The urinary excretion of cyclo-C is rapid; Five hours after parenteral administration, 60% of the given drug is excreted; 45% as cyclo-C, 10% as ara-C, and about 5% as ara-U. In contrast, after similar injections of ara-C, 45% of the drug is excreted; 33% as ara-C and 12% as ara-U. When compared with those in human and mouse tissues, the deoxycytidine deaminase levels in dog tissues are extremely low. This agrees with the finding of low ara-U levels in dog plasma and urine after administering cyclo-C or ara-C. Regardless whether cyclo-C or ara-C is injected, the plasma decay curve of the resultant ara-C is biphasic, with calculated half-lives of 40 min and 2-2.5 hr. However, if ara-C is given, the plasma ara-C peak level is higher. Higher ara-C levels are also maintained throughout the measured 5 hr. There are no differences in pharmacologic disposition after iv, sc, or im administration of ara-C. This is also true for cyclo-C. These findings suggest that for both drugs, the above routes of administration may be equally effective. Neither cyclo-C nor ara-C is well absorbed after oral administration, and the drug concentration in the plasma is too low to be measurable. Whether the dog is fasted overnight or fed, the drug is excreted slowly. In 5 hr. no more than 3% is excreted, and by 12 hr. only 10% is excreted."}
{"id": "PMID:240663", "title": "The use of zonal ultracentrifugation in the investigation of the binding of delta9-tetrahydrocannabinol by plasma lipoproteins.", "content": "The major classes of lipoprotein, very low density, low density, and high density, as well as the lipoprotein-free protein were isolated from plasma by rate-zonal centrifugation. Fractionation of plasma after the addition of delta9-tetrahydrocannabinol (THC) showed that over 60% of the drug is associated with the lipoprotein; the remainder of the drug appears to be bound by albumin. In human plasma the low density lipoprotein is the major lipoprotein; in rat plasma the very low density and high density lipoproteins predominate. The distribution of THC in the lipoprotein reflected this species difference. In both species the distribution of THC among the lipoproteins appears to be related to their content of neutral lipid or total lipid rather than that of phospholipid or protein. Fractionation of plasma after the addition of estradiol, imipramine, prostaglandin E2, digitoxin, or dicumarol demonstrated that the lipoproteins contribute little to their binding. Thus, even among lipid-soluble compounds, the binding of THC in plasma is unusual.", "contents": "The use of zonal ultracentrifugation in the investigation of the binding of delta9-tetrahydrocannabinol by plasma lipoproteins. The major classes of lipoprotein, very low density, low density, and high density, as well as the lipoprotein-free protein were isolated from plasma by rate-zonal centrifugation. Fractionation of plasma after the addition of delta9-tetrahydrocannabinol (THC) showed that over 60% of the drug is associated with the lipoprotein; the remainder of the drug appears to be bound by albumin. In human plasma the low density lipoprotein is the major lipoprotein; in rat plasma the very low density and high density lipoproteins predominate. The distribution of THC in the lipoprotein reflected this species difference. In both species the distribution of THC among the lipoproteins appears to be related to their content of neutral lipid or total lipid rather than that of phospholipid or protein. Fractionation of plasma after the addition of estradiol, imipramine, prostaglandin E2, digitoxin, or dicumarol demonstrated that the lipoproteins contribute little to their binding. Thus, even among lipid-soluble compounds, the binding of THC in plasma is unusual."}
{"id": "PMID:240660", "title": "Further studies on medazepam metabolism in the rat.", "content": "Previous studies with 9000g supernatant fractions of rat liver revealed that the 1,4-benzodiazepine, medazepam, was converted to N-desmethyldiazepam by a series of reactions including hydroxylation, N-demethylation, and dehydrogenation. The present study was designed to determine if the pathway via diazepam as intermediate, which is one of three possible pathways, is the major route in vivo in the rat for N-desmethyldiazepam formation from medazepam. Measurement of the levels of labeled drug and metabolites in blood, brain, lung, heart, and muscle 5 min after the oral administration of approximately equivalent doses of [14C]medazepam hydrochloride, [14C]diazepam, or N-desmethyl[14C]medazepam revealed that each drug was both rapidly absorbed and oxidatively metabolized in the rat. At 1 hr. the tissue levels of labeled N-desmethyldiazepam were highest after N-desmethyl-[14C]medazepam, intermediate after [14C]medazepam hydrochloride and lowest after [14C]diazepam. These results indicated that in the formation of N-desmethyldiazepam from medazepam in the rat there is a substantial preference for the pathway via N-desmethylmedazepam over that in which diazepam is an intermediate. From consideration of the limited data available, it is suggested that this same preference in pathways may also hold true in humans.", "contents": "Further studies on medazepam metabolism in the rat. Previous studies with 9000g supernatant fractions of rat liver revealed that the 1,4-benzodiazepine, medazepam, was converted to N-desmethyldiazepam by a series of reactions including hydroxylation, N-demethylation, and dehydrogenation. The present study was designed to determine if the pathway via diazepam as intermediate, which is one of three possible pathways, is the major route in vivo in the rat for N-desmethyldiazepam formation from medazepam. Measurement of the levels of labeled drug and metabolites in blood, brain, lung, heart, and muscle 5 min after the oral administration of approximately equivalent doses of [14C]medazepam hydrochloride, [14C]diazepam, or N-desmethyl[14C]medazepam revealed that each drug was both rapidly absorbed and oxidatively metabolized in the rat. At 1 hr. the tissue levels of labeled N-desmethyldiazepam were highest after N-desmethyl-[14C]medazepam, intermediate after [14C]medazepam hydrochloride and lowest after [14C]diazepam. These results indicated that in the formation of N-desmethyldiazepam from medazepam in the rat there is a substantial preference for the pathway via N-desmethylmedazepam over that in which diazepam is an intermediate. From consideration of the limited data available, it is suggested that this same preference in pathways may also hold true in humans."}
{"id": "PMID:240669", "title": "[Gerontological and geriatric problems in stomatology. 1: Effects of age related physical changes on prosthetic therapy].", "content": "Morphological changes in the mouth due to age, e.g. changes in the oral mucosa, the blood supply of the lower jaw, and the nervous system, make variations of prosthetical therapy necessary. By means of a classification of old-age patients, the significance of such variations for the prosthetical treatment of partially edentulous jaws is demonstrated.", "contents": "[Gerontological and geriatric problems in stomatology. 1: Effects of age related physical changes on prosthetic therapy]. Morphological changes in the mouth due to age, e.g. changes in the oral mucosa, the blood supply of the lower jaw, and the nervous system, make variations of prosthetical therapy necessary. By means of a classification of old-age patients, the significance of such variations for the prosthetical treatment of partially edentulous jaws is demonstrated."}
{"id": "PMID:240661", "title": "The disposition of ftorafur in rats after intravenous administration.", "content": "The excretion, distribution, and metabolism of ftorafur was studied in rats following a single intravenous injection of radioactively labeled drug. Approximately 55% of the administered radioactivity was excreted as 14CO2, while 23% was eliminated via the urinary route in 24 hr. Less than 2% was excreted in the feces. The major excretory product found in the urine was unmetabolized ftorafur. However, the proportions of radioactively labeled metabolites such as 5-fluorouracil and urea increased with time after injection. The half-life of ftorafur in plasma was estimated to be approximately 5 hr. The drug was fairly evenly distributed to liver, small intestine, spleen, kidney, and brain. Highest initial concentrations were found in the liver, which also retained more drug for a longer period than the other tissues. The liver was also found to contain the highest initial proportions of 5-fluorouracil and its metabolites. The results obtained are consistent with the suggestion that ftorafur may be a depot form of 5-fluorouracil and that the liver may be the primary site at which the latter drug is released in vivo.", "contents": "The disposition of ftorafur in rats after intravenous administration. The excretion, distribution, and metabolism of ftorafur was studied in rats following a single intravenous injection of radioactively labeled drug. Approximately 55% of the administered radioactivity was excreted as 14CO2, while 23% was eliminated via the urinary route in 24 hr. Less than 2% was excreted in the feces. The major excretory product found in the urine was unmetabolized ftorafur. However, the proportions of radioactively labeled metabolites such as 5-fluorouracil and urea increased with time after injection. The half-life of ftorafur in plasma was estimated to be approximately 5 hr. The drug was fairly evenly distributed to liver, small intestine, spleen, kidney, and brain. Highest initial concentrations were found in the liver, which also retained more drug for a longer period than the other tissues. The liver was also found to contain the highest initial proportions of 5-fluorouracil and its metabolites. The results obtained are consistent with the suggestion that ftorafur may be a depot form of 5-fluorouracil and that the liver may be the primary site at which the latter drug is released in vivo."}
{"id": "PMID:240670", "title": "[Comparative in vitro study on cellular reactions to soluble components of EBA and phosphate cement].", "content": "While the eluate of EBA cement does not have any toxic effect on the cell populations, the cells are noticeably damaged by the pH-corrected eluate of freshly mixed phosphate cement. Comparison between the cellular reaction to eluates and the solubility of the cements shows that the toxic effect is not a priori dependent on the composition of the material, but on the degree of dissolution which is primarily determined by the environment and the mixture ratio. The solutions of cement powder do not have any irritating effect on the cultivated cells. However, due to its content of eugenol, the EBA cement fluid solved in a considerably weaker concentration in the culture medium than the phosphate cement fluid damages the cells to such an extent that they die.", "contents": "[Comparative in vitro study on cellular reactions to soluble components of EBA and phosphate cement]. While the eluate of EBA cement does not have any toxic effect on the cell populations, the cells are noticeably damaged by the pH-corrected eluate of freshly mixed phosphate cement. Comparison between the cellular reaction to eluates and the solubility of the cements shows that the toxic effect is not a priori dependent on the composition of the material, but on the degree of dissolution which is primarily determined by the environment and the mixture ratio. The solutions of cement powder do not have any irritating effect on the cultivated cells. However, due to its content of eugenol, the EBA cement fluid solved in a considerably weaker concentration in the culture medium than the phosphate cement fluid damages the cells to such an extent that they die."}
{"id": "PMID:240671", "title": "[Action of delta 9 tetrahydrocannabinol on the central cardiovascular regulation : mechanism and localization].", "content": "Delta9-tetrahydrocannabinol (30-300 mug.kg-1 i.v.) induced in cats and dogs a decrease in blood pressure and heart rate. This decrease appears to be centrally mediated. In fact, the splanchnic and cardiac discharges were reduced in intact animals as well as in debuffered cats ruling out a reflexly mediated action. The mechanism of this central decrease in the sympathetic tone appears to be different from the mechanism of the reduction induced by clonidine or by narcotic analgesics agents. In fact, piperoxan (1 mg.kg-1 i.v.), an alpha adrenoceptor blocking agent, antagonized or reversed the centrally mediated reduction in the sympathetic tone induced by clonidine or L-dopa, but did not change the effects of narcotic analgesic agents and of delta9-tetrahydrocannabinol. Naloxone (30 mug.kg-1 i.v.) prevented or reversed the cardiovascular effects of fentanyl and the reduction in splanchnic discharges induced by this agent, but no change was found after naloxone in the effects of clonidine or delta9-tetrahydrocannabinol. The pressor response to high frequency stimulation of the medulla oblongata was abolished by small doses of delta9-tetrahydrocannabinol. This agent did not reduce the pressor response to stimulation of the posterior hypothalamus induced by supramaximal stimulation and did not alter the hypertensive effect induced by stimulation of the cervical spinal cord. Medulla oblogata appears therefore to be the main site of action.", "contents": "[Action of delta 9 tetrahydrocannabinol on the central cardiovascular regulation : mechanism and localization]. Delta9-tetrahydrocannabinol (30-300 mug.kg-1 i.v.) induced in cats and dogs a decrease in blood pressure and heart rate. This decrease appears to be centrally mediated. In fact, the splanchnic and cardiac discharges were reduced in intact animals as well as in debuffered cats ruling out a reflexly mediated action. The mechanism of this central decrease in the sympathetic tone appears to be different from the mechanism of the reduction induced by clonidine or by narcotic analgesics agents. In fact, piperoxan (1 mg.kg-1 i.v.), an alpha adrenoceptor blocking agent, antagonized or reversed the centrally mediated reduction in the sympathetic tone induced by clonidine or L-dopa, but did not change the effects of narcotic analgesic agents and of delta9-tetrahydrocannabinol. Naloxone (30 mug.kg-1 i.v.) prevented or reversed the cardiovascular effects of fentanyl and the reduction in splanchnic discharges induced by this agent, but no change was found after naloxone in the effects of clonidine or delta9-tetrahydrocannabinol. The pressor response to high frequency stimulation of the medulla oblongata was abolished by small doses of delta9-tetrahydrocannabinol. This agent did not reduce the pressor response to stimulation of the posterior hypothalamus induced by supramaximal stimulation and did not alter the hypertensive effect induced by stimulation of the cervical spinal cord. Medulla oblogata appears therefore to be the main site of action."}
{"id": "PMID:240672", "title": "[Prolonged-action drugs in psychiatric therapeutics : gaps and needs].", "content": "The most accomplished model in this type of therapy is presently that of the long-acting neuroleptic (L.A.N.). Some target-symptoms are privileged : schizophrenic inertia (piportil or flupentixol derivatives), delusions (fluphenazine derivatives). But on the other hand, a sedative action has not been considered as benefic in long-acting drugs, and we're still in need of an L.A.N. whose hallucinolytic action would favourably compared with haloperidol. In the field of antidepressants, improvements appear as necessary. It is highly desirable to find compounds whose action would be really powerful, whose duration of action would last more than 24 or 48 hours ; the compound being administred either as an embonate or intra-muscularly in an attempt to limit the risks of suicide. Researches are being conducted : 1) to obtain long-acting antiparkinsonian correctors ; 2) to find out some form of lithium salts which, after one administration, would allow a stable nycthemeral lithiemy.", "contents": "[Prolonged-action drugs in psychiatric therapeutics : gaps and needs]. The most accomplished model in this type of therapy is presently that of the long-acting neuroleptic (L.A.N.). Some target-symptoms are privileged : schizophrenic inertia (piportil or flupentixol derivatives), delusions (fluphenazine derivatives). But on the other hand, a sedative action has not been considered as benefic in long-acting drugs, and we're still in need of an L.A.N. whose hallucinolytic action would favourably compared with haloperidol. In the field of antidepressants, improvements appear as necessary. It is highly desirable to find compounds whose action would be really powerful, whose duration of action would last more than 24 or 48 hours ; the compound being administred either as an embonate or intra-muscularly in an attempt to limit the risks of suicide. Researches are being conducted : 1) to obtain long-acting antiparkinsonian correctors ; 2) to find out some form of lithium salts which, after one administration, would allow a stable nycthemeral lithiemy."}
{"id": "PMID:240673", "title": "Extraction and partial purification of prolactin-release stimulating factor in bovine hypothalami.", "content": "Partial purification of prolactin-release stimulating factor (PRF) was performed by Sephadex G-25 gel filtration of bovine hypothalamic extracts. PRF activity was evaluated on the basis of the measurement of immunoreactive prolactin released from the isolated rat hemipituitary in vitro. PRF activity was found in the fractions with Kav=0-0.49 and prolactin-release inhibiting activity was also detected in the fractions with Kav=0.69-0.89. The dose-response relationship was established between the partially purified PRF and its activity. The elution position of the partially purified PRF preceded that of TRH on Sephadex G-25. TRH at the dose of 100 nM stimulated the release of TSH in vitro, but not the release of prolactin. These results may indicate that there exists PRF with a relatively high molecular weight in the bovine hypothalamus.", "contents": "Extraction and partial purification of prolactin-release stimulating factor in bovine hypothalami. Partial purification of prolactin-release stimulating factor (PRF) was performed by Sephadex G-25 gel filtration of bovine hypothalamic extracts. PRF activity was evaluated on the basis of the measurement of immunoreactive prolactin released from the isolated rat hemipituitary in vitro. PRF activity was found in the fractions with Kav=0-0.49 and prolactin-release inhibiting activity was also detected in the fractions with Kav=0.69-0.89. The dose-response relationship was established between the partially purified PRF and its activity. The elution position of the partially purified PRF preceded that of TRH on Sephadex G-25. TRH at the dose of 100 nM stimulated the release of TSH in vitro, but not the release of prolactin. These results may indicate that there exists PRF with a relatively high molecular weight in the bovine hypothalamus."}
{"id": "PMID:240674", "title": "Effects of crude oil on the feeding behaviour of the zoanthid Palythoa variabilis.", "content": "Palythoa variabilis (Duerden 1898) has a well-coordinated, sterotyped feeding response similar to that described for other zoanthids. The feeding reaction can be elicited by the heterocyclic amino acid proline and by some of its analogs. The addition of an OH group (hydroxyproline) or of a glycyl group (prolylglycine) annuls the activity of the proline molecule. Substitutions (thiazolidine-4-carboxylic acid) or additions (glycylproline) to the amino group do not alter the effectivity of the activator. The size of the ring can be altered within certain limits (azetidine-2-carbocylic acid and pipecolic acid) without affecting the activity of the molecule. Feeding reactions culminating with ingestion can be elicited by Marine Diesel and Bunker-C oils. Exposure to oil affects the ability of polyps to discriminate between inert and chemically active particles for 3 to 5 days; responses to proline are not altered for at least 3 days following the exposure, but become slower and are present in fewer polyps after that period. Oil is retained in the coelenteron for several days following exposure and is periodically released in the form of timy droplets.", "contents": "Effects of crude oil on the feeding behaviour of the zoanthid Palythoa variabilis. Palythoa variabilis (Duerden 1898) has a well-coordinated, sterotyped feeding response similar to that described for other zoanthids. The feeding reaction can be elicited by the heterocyclic amino acid proline and by some of its analogs. The addition of an OH group (hydroxyproline) or of a glycyl group (prolylglycine) annuls the activity of the proline molecule. Substitutions (thiazolidine-4-carboxylic acid) or additions (glycylproline) to the amino group do not alter the effectivity of the activator. The size of the ring can be altered within certain limits (azetidine-2-carbocylic acid and pipecolic acid) without affecting the activity of the molecule. Feeding reactions culminating with ingestion can be elicited by Marine Diesel and Bunker-C oils. Exposure to oil affects the ability of polyps to discriminate between inert and chemically active particles for 3 to 5 days; responses to proline are not altered for at least 3 days following the exposure, but become slower and are present in fewer polyps after that period. Oil is retained in the coelenteron for several days following exposure and is periodically released in the form of timy droplets."}
{"id": "PMID:240675", "title": "Adenosine deaminase in chicken-egg yolk and its relation to homologous enzymes in liver and plasma of the adult hen.", "content": "Chicken egg yolk contains an adenosine deaminase that was investigated after purifying about 500 times. It has a pH optimum at 6.5, aKm of 6.6 times 10(-5) mol/l and an approximate molecular weight of 14000; higher molecular forms could not be detected. It was compared with the adenosine deaminases of chicken liver and blood plasma. From this comparison it is evident that this protein has undergone certain changes during the successive events leading to its final structure (secretion by the liver, transport through blood plasma to the oocytes and development of the egg): a common subunit with an approximate molecular weight of 15000 may be the basis of the physiological diversifications. Substrate specificity of the purified extracts extends to cytidine and guanosine also, although certain observations point to different enzymes being involved. Deoxyadenosine is also deaminated. Cu2+, Zn2+, and Pb2+ are inhibiting and free -SH seems essential for activity.", "contents": "Adenosine deaminase in chicken-egg yolk and its relation to homologous enzymes in liver and plasma of the adult hen. Chicken egg yolk contains an adenosine deaminase that was investigated after purifying about 500 times. It has a pH optimum at 6.5, aKm of 6.6 times 10(-5) mol/l and an approximate molecular weight of 14000; higher molecular forms could not be detected. It was compared with the adenosine deaminases of chicken liver and blood plasma. From this comparison it is evident that this protein has undergone certain changes during the successive events leading to its final structure (secretion by the liver, transport through blood plasma to the oocytes and development of the egg): a common subunit with an approximate molecular weight of 15000 may be the basis of the physiological diversifications. Substrate specificity of the purified extracts extends to cytidine and guanosine also, although certain observations point to different enzymes being involved. Deoxyadenosine is also deaminated. Cu2+, Zn2+, and Pb2+ are inhibiting and free -SH seems essential for activity."}
{"id": "PMID:240676", "title": "Relation between structure and function in some partially synthetic ribonucleases S'. Enzymic and spectroscopic investigation on [Orn10, Asn14]-RNase S' and 1epsilon, 7epsilon, 10delta-triguanidino-[Orn10, Asn14]-RNase S'.", "content": "Some analogues have been prepared of S-peptide, the peptide obtained together with S-protein from subtilisn-modified beef pancreatic R Nase A. The syntheses are described of [Orn10, Asn14]-S-peptide and 1epsilon, 7epsilon, 10delta-triguanidino-[Orn10, Asn14]-S-peptide. The S-peptide analogues are able to activate S-protein at the level of the parent [Orn10]-S-peptide and 1epsilon, 7epsilon-diguanidino-S-peptide respectively, although at high peptide-to-protein molar ratios. After their recombination with S-protein the buried character of Tyr-25 was restored, as judged from difference absorption and circular dichroism spectra in the near-ultraviolet region. These findings indicate that the asparaginyl residue is a possible naturally occurring substituent in the R Nase A sequences whose state of amidation in position 14 has not yet been defined.", "contents": "Relation between structure and function in some partially synthetic ribonucleases S'. Enzymic and spectroscopic investigation on [Orn10, Asn14]-RNase S' and 1epsilon, 7epsilon, 10delta-triguanidino-[Orn10, Asn14]-RNase S'. Some analogues have been prepared of S-peptide, the peptide obtained together with S-protein from subtilisn-modified beef pancreatic R Nase A. The syntheses are described of [Orn10, Asn14]-S-peptide and 1epsilon, 7epsilon, 10delta-triguanidino-[Orn10, Asn14]-S-peptide. The S-peptide analogues are able to activate S-protein at the level of the parent [Orn10]-S-peptide and 1epsilon, 7epsilon-diguanidino-S-peptide respectively, although at high peptide-to-protein molar ratios. After their recombination with S-protein the buried character of Tyr-25 was restored, as judged from difference absorption and circular dichroism spectra in the near-ultraviolet region. These findings indicate that the asparaginyl residue is a possible naturally occurring substituent in the R Nase A sequences whose state of amidation in position 14 has not yet been defined."}
{"id": "PMID:240677", "title": "Quantitative analysis of mixed association between different protein molecules. Physico-chemical and enzymatic properties of rat-liver glutamate dehydrogenase.", "content": "The theoretical and experimental analysis of a reversible association-dissociation equilibrium between different proteins (mixed association) is described. The experiments were performed with glutamate dehydrogenases from beef and rat liver. These enzymes are different, especially with respect to their association behavior. The association constant of rat liver glutamate dehydrogenase has been determined by light-scattering measurements. Its value (1.3 x 10(-4) M(-1)) is much lower than that of the beef liver enzyme, but the difference in the free association energy is only 30%. Association between these two enzymes is observed, also employing light-scattering experiments. Theoretical curves for mixed associating systems have been calculated and by comparison with these curves the mixed association constant could be determined. Since the free association energy of the mixed association is very near to the arithmetic mean between the values for the pure enzymes, the association interactions appear to be additive. The model of an open association with a virial coefficient is also true for the rat enzyme and the mixed association. The ultracentrifuge data are also explained by the same model and yield a similar value for the mixed association constant. Differences in the enzyme kinetics are small, but a somewhat reduced lifetime of the ternary complexes with the coenzymes and with subs-rates or GTP can be concluded for the rat liver enzyme. The circular dichroism measurements indicate no significant difference in the dissociation constants of the nucleotides, but the different amplitudes of the ellipticity indicate small differences in the electrical environment of the active center.", "contents": "Quantitative analysis of mixed association between different protein molecules. Physico-chemical and enzymatic properties of rat-liver glutamate dehydrogenase. The theoretical and experimental analysis of a reversible association-dissociation equilibrium between different proteins (mixed association) is described. The experiments were performed with glutamate dehydrogenases from beef and rat liver. These enzymes are different, especially with respect to their association behavior. The association constant of rat liver glutamate dehydrogenase has been determined by light-scattering measurements. Its value (1.3 x 10(-4) M(-1)) is much lower than that of the beef liver enzyme, but the difference in the free association energy is only 30%. Association between these two enzymes is observed, also employing light-scattering experiments. Theoretical curves for mixed associating systems have been calculated and by comparison with these curves the mixed association constant could be determined. Since the free association energy of the mixed association is very near to the arithmetic mean between the values for the pure enzymes, the association interactions appear to be additive. The model of an open association with a virial coefficient is also true for the rat enzyme and the mixed association. The ultracentrifuge data are also explained by the same model and yield a similar value for the mixed association constant. Differences in the enzyme kinetics are small, but a somewhat reduced lifetime of the ternary complexes with the coenzymes and with subs-rates or GTP can be concluded for the rat liver enzyme. The circular dichroism measurements indicate no significant difference in the dissociation constants of the nucleotides, but the different amplitudes of the ellipticity indicate small differences in the electrical environment of the active center."}
{"id": "PMID:240678", "title": "Studies of glutamate dehydrogenase: analysis of functional areas and functional groups.", "content": "1. It is shown by limited tryptic digestion of beef liver glutamate dehydrogenase under native conditions that the amino terminus of the polypeptide chain is located at the surface of the molecule. End-group analysis after trypsin treatment yields aspartic acid as the new N-terminal amino acid while the C-terminal threonine remains unchanged. 2. NADH, especially in the presence of 2-oxoglutarate, protects the enzyme against tryptic degradation. In the absence of the coenzyme, glutamate dehydrogenase is rapidly inactivated. 3. The regulatory effects of ADP and GTP are only slightly altered by trypsin. A small shift of the pH dependence of the activation by ADP is observed. 4. The quaternary structure of the unimer of the enzyme is not affected by limited tryptic digestion indicating that the N-terminal part of the polypeptide chain is not located in the contact domains between the polypeptide  chains. The association of the hexamer to large associated particles is reduced but not abolished. 5. It is shown by treatment of the enzyme with iodo[2(-14)C]acetic acid as well as with Ellman's reagent that the six - SH groups of the polypeptide chain are buried and not accessible to these reagents in phosphate buffer. In Tris buffer they become exposed and react in the order 89, 55, 197, 115, 270, 319. This together with the result that in Tris buffer the rat of inactivation caused by trypsin is higher than in phosphate buffer indicates that Tris buffer changes drastically the properties of the enzyme. 6. Cross-linking of the enzyme molecule with bifunctional reagents and subsequent dodecylsulfate-polyacrylamide electrophoresis shows that the six identical polypeptide chains are arranged in two groups of three. 7. The implications of these results for the tertiary and quaternary structure of beef liver glutamate dehydrogenase are discussed.", "contents": "Studies of glutamate dehydrogenase: analysis of functional areas and functional groups. 1. It is shown by limited tryptic digestion of beef liver glutamate dehydrogenase under native conditions that the amino terminus of the polypeptide chain is located at the surface of the molecule. End-group analysis after trypsin treatment yields aspartic acid as the new N-terminal amino acid while the C-terminal threonine remains unchanged. 2. NADH, especially in the presence of 2-oxoglutarate, protects the enzyme against tryptic degradation. In the absence of the coenzyme, glutamate dehydrogenase is rapidly inactivated. 3. The regulatory effects of ADP and GTP are only slightly altered by trypsin. A small shift of the pH dependence of the activation by ADP is observed. 4. The quaternary structure of the unimer of the enzyme is not affected by limited tryptic digestion indicating that the N-terminal part of the polypeptide chain is not located in the contact domains between the polypeptide  chains. The association of the hexamer to large associated particles is reduced but not abolished. 5. It is shown by treatment of the enzyme with iodo[2(-14)C]acetic acid as well as with Ellman's reagent that the six - SH groups of the polypeptide chain are buried and not accessible to these reagents in phosphate buffer. In Tris buffer they become exposed and react in the order 89, 55, 197, 115, 270, 319. This together with the result that in Tris buffer the rat of inactivation caused by trypsin is higher than in phosphate buffer indicates that Tris buffer changes drastically the properties of the enzyme. 6. Cross-linking of the enzyme molecule with bifunctional reagents and subsequent dodecylsulfate-polyacrylamide electrophoresis shows that the six identical polypeptide chains are arranged in two groups of three. 7. The implications of these results for the tertiary and quaternary structure of beef liver glutamate dehydrogenase are discussed."}
{"id": "PMID:240679", "title": "Bacterial respiration-linked proton translocation and its relationship to respiratory-chain composition.", "content": "1. The relationship between chain composition and the efficiency of respiration-linked proton translocation was studied in nine bacterial species of widely differing taxonomic and ecological status. 2. All the bacteria investigated contained respiratory chain dehydrogenases, ubiquinone and/or menaquinone, cytochrome b and cytochrome oxidase aa3 and/or o. In addition, some of these organisms also contained pyridine nucleotide transhydrogenase and/or cytochrome c. 3. leads to H+/O ratios of whole cell suspensions oxidising endogenous substrates were in the approximate range 4-8 mol H+ translocated per g-atom oxygen consumed. It was concluded from the observed leads to H+/O ratios of cells loaded with specific substrates that proton-translocating loops 1 and 2 were present in all of the organisms investigated, but that loops 0 and 3 were dependent upon the presence of pyridine nucleotide transhydrogenase and cytochrome c respectively. 4. The wide range in energy conservation efficiency which was observed in these organisms is discussed in relation to their respiratory chain composition and natural habitat.", "contents": "Bacterial respiration-linked proton translocation and its relationship to respiratory-chain composition. 1. The relationship between chain composition and the efficiency of respiration-linked proton translocation was studied in nine bacterial species of widely differing taxonomic and ecological status. 2. All the bacteria investigated contained respiratory chain dehydrogenases, ubiquinone and/or menaquinone, cytochrome b and cytochrome oxidase aa3 and/or o. In addition, some of these organisms also contained pyridine nucleotide transhydrogenase and/or cytochrome c. 3. leads to H+/O ratios of whole cell suspensions oxidising endogenous substrates were in the approximate range 4-8 mol H+ translocated per g-atom oxygen consumed. It was concluded from the observed leads to H+/O ratios of cells loaded with specific substrates that proton-translocating loops 1 and 2 were present in all of the organisms investigated, but that loops 0 and 3 were dependent upon the presence of pyridine nucleotide transhydrogenase and cytochrome c respectively. 4. The wide range in energy conservation efficiency which was observed in these organisms is discussed in relation to their respiratory chain composition and natural habitat."}
{"id": "PMID:240680", "title": "Synthesis and hydrolysis by pepsin and trypsin of a cyclic hexapeptide containing lysine and phenylalanine.", "content": "1. A cyclic hexapeptide, cyclo(-Gly2-Phe2-Gly-Lys-), and the corresponding open-chain hexapeptides, Gly2-Phe2-Gly-Lys and Phe-Gly-Lys-Gly2-Phe, have been synthesized and their susceptibilities to the hydrolytic action of pepsin and trypsin were determined. 2. The cyclic peptide was hydrolyzed slowly by trypsin to a hexapeptide Gly2-Phe2-Gly-Lys, the value of the Michaelis constant for this reaction being Km equals 0.00022 M. 3. The cyclic peptide was not cleaved by pepsin at all, but Gly2-Phe2-Gly-Lys was hydrolyzed rapidly at a Phe-Phe bond; Km equals 0.0091 M. 4. The cyclic peptide inhibits the hydrolysis of Gly2-Phe2-Gly-Lys by pepsin in a linear non-competitive manner, the value of the inhibition constant being Ki equals 0.004 M.", "contents": "Synthesis and hydrolysis by pepsin and trypsin of a cyclic hexapeptide containing lysine and phenylalanine. 1. A cyclic hexapeptide, cyclo(-Gly2-Phe2-Gly-Lys-), and the corresponding open-chain hexapeptides, Gly2-Phe2-Gly-Lys and Phe-Gly-Lys-Gly2-Phe, have been synthesized and their susceptibilities to the hydrolytic action of pepsin and trypsin were determined. 2. The cyclic peptide was hydrolyzed slowly by trypsin to a hexapeptide Gly2-Phe2-Gly-Lys, the value of the Michaelis constant for this reaction being Km equals 0.00022 M. 3. The cyclic peptide was not cleaved by pepsin at all, but Gly2-Phe2-Gly-Lys was hydrolyzed rapidly at a Phe-Phe bond; Km equals 0.0091 M. 4. The cyclic peptide inhibits the hydrolysis of Gly2-Phe2-Gly-Lys by pepsin in a linear non-competitive manner, the value of the inhibition constant being Ki equals 0.004 M."}
{"id": "PMID:240681", "title": "The plant aminoacyl-tRNA synthetases. Purification and characterization of valyl-tRNA, tryptophanyl-tRNA and seryl-tRNA synthetases from yellow-lupin seeds.", "content": "Valyl-tRNA, tryptophanyl-tRNA, and seryl-tRNA synthetases from yellow lupin seeds Lupinus luteus were purified to homogeneity by ammonium sulfate fractionation, hydrophobic chromatography on aminohexyl-Sepharose column and affinity chromatography on tRNA-Sepharose column. Valyl-tRNA synthetase consists of one polypeptide chain of molecular weight 125000 as judged by Sephadex G-200 gel filtration and dodecylsulfate-polyacrylamide gel electrophoresis in the presence of reducing agent. Seryl-tRNA synthetase, Mr equals 110000, is composed of two 55000-Mr subunits. Tryptophanyl-tRNA synthetase exhibits molecular weight of 200000 on Sephadex G-200 and 37000 in dodecylsulfate-polyacrylamide gel electrophoresis. This indicates that tryptophanyl-tRNA synthetase consists of several subunits (probably four). Since the seryl-tRNA synthetase exhibits the same mobility on dodecylsulfate-polyacrylamide gels both in the presence and absence of reducing agent it is concluded that there is no covalent bond(s) between the subunits of the enzyme. There is also no covalent bond(s) between the subunits of tryptophanyl-tRNA synthetase. Effect of anti-sulfhydryl reagents, monovalent salts, pH and different buffers on activity of the three synthetases is described. Kinetic constants for the substrates of the synthetases are also given. dATP is a substrate for seryl-tRNA synthetase but not for valyl-tRNA and tryptophanyl-tRNA synthetases.", "contents": "The plant aminoacyl-tRNA synthetases. Purification and characterization of valyl-tRNA, tryptophanyl-tRNA and seryl-tRNA synthetases from yellow-lupin seeds. Valyl-tRNA, tryptophanyl-tRNA, and seryl-tRNA synthetases from yellow lupin seeds Lupinus luteus were purified to homogeneity by ammonium sulfate fractionation, hydrophobic chromatography on aminohexyl-Sepharose column and affinity chromatography on tRNA-Sepharose column. Valyl-tRNA synthetase consists of one polypeptide chain of molecular weight 125000 as judged by Sephadex G-200 gel filtration and dodecylsulfate-polyacrylamide gel electrophoresis in the presence of reducing agent. Seryl-tRNA synthetase, Mr equals 110000, is composed of two 55000-Mr subunits. Tryptophanyl-tRNA synthetase exhibits molecular weight of 200000 on Sephadex G-200 and 37000 in dodecylsulfate-polyacrylamide gel electrophoresis. This indicates that tryptophanyl-tRNA synthetase consists of several subunits (probably four). Since the seryl-tRNA synthetase exhibits the same mobility on dodecylsulfate-polyacrylamide gels both in the presence and absence of reducing agent it is concluded that there is no covalent bond(s) between the subunits of the enzyme. There is also no covalent bond(s) between the subunits of tryptophanyl-tRNA synthetase. Effect of anti-sulfhydryl reagents, monovalent salts, pH and different buffers on activity of the three synthetases is described. Kinetic constants for the substrates of the synthetases are also given. dATP is a substrate for seryl-tRNA synthetase but not for valyl-tRNA and tryptophanyl-tRNA synthetases."}
{"id": "PMID:240682", "title": "Isoenzymes of p-coumarate: CoA ligase from cell suspension cultures of Glycine max.", "content": "Two isoenzymes of p-coumarate: CoA ligase were isolated from cell suspension cultures of soybean (Glycine max L., var. Mandarin). Separation and partial purification of the enzymes were achieved by precipitation with MnCl2 and (NH4)2SO4, and column chromatography on DEAE-cellulose, Sephadex G-100 and hydroxyapatite. The isoenzymes had approximately the same molecular weight, but differed significantly with respect to their substrate specificity, their inhibition constants for AMP, their dependence on pH and ionic strength for optimum activity, and their fractionation pattern during the purification procedure or upon analytical disc-gel electrophoresis. Both coumarate: CoA ligases were specific for the activation of various substituted cinnamic acids. Of the cinnamic acids tested, ferulic, sinapic, 5-hydroxyferulic, p-coumaric, and caffeic acids were the substrates with the lowest apparent Km values (on all the order of 1 to 4 x 10(-5) M) for isoenzyme 1. The lowest apparent Km values (from about 1 to 9 x 10(-5) M) for isoenzyme 2 were obtained for caffeic, p-coumaric, m-coumaric, and o-coumaric acids. Sinapic acid and several methoxycinnamic acids were efficient substrates of isoenzyme 1 but were not activated at all by isoenzyme 2. The possible roles of the two p-coumarate: CoA ligase isoenzymes in the phenylpropanoid metabolism of the cell cultures are discussed.", "contents": "Isoenzymes of p-coumarate: CoA ligase from cell suspension cultures of Glycine max. Two isoenzymes of p-coumarate: CoA ligase were isolated from cell suspension cultures of soybean (Glycine max L., var. Mandarin). Separation and partial purification of the enzymes were achieved by precipitation with MnCl2 and (NH4)2SO4, and column chromatography on DEAE-cellulose, Sephadex G-100 and hydroxyapatite. The isoenzymes had approximately the same molecular weight, but differed significantly with respect to their substrate specificity, their inhibition constants for AMP, their dependence on pH and ionic strength for optimum activity, and their fractionation pattern during the purification procedure or upon analytical disc-gel electrophoresis. Both coumarate: CoA ligases were specific for the activation of various substituted cinnamic acids. Of the cinnamic acids tested, ferulic, sinapic, 5-hydroxyferulic, p-coumaric, and caffeic acids were the substrates with the lowest apparent Km values (on all the order of 1 to 4 x 10(-5) M) for isoenzyme 1. The lowest apparent Km values (from about 1 to 9 x 10(-5) M) for isoenzyme 2 were obtained for caffeic, p-coumaric, m-coumaric, and o-coumaric acids. Sinapic acid and several methoxycinnamic acids were efficient substrates of isoenzyme 1 but were not activated at all by isoenzyme 2. The possible roles of the two p-coumarate: CoA ligase isoenzymes in the phenylpropanoid metabolism of the cell cultures are discussed."}
{"id": "PMID:240683", "title": "Fractionation of horseradish peroxidase by preparative isoelectric focusing, gel chromatography and ion-exchange chromatography.", "content": "Horseradish peroxidase has been fractionated by preparative isoelectric focusing in a density gradient and in a layer of granulated gel using pH-3-10 and narrow-pH-range carrier ampholytes at different total enzyme loads. The resolution of peroxidase isoenzymes in preparative-layer isoelectric focusing was comparable to that obtained by analytical thin-layer isoelectric focusing. Isoelectrically homogeneous isoenzymes could be isolated with good recovery in a single fractionation step. Despite the excellent separation of the individual isoenzymes by isoelectric focusing in gel layers, an effective purification, indicated by the absorbance ratio A403mn/A278nm, could not be achieved by focusing applied as a single step. By different fractionation sequences combining gel chromatography, ion-exchange chromatography, and isoelectric focusing, individual isoenzymes with a high purity and homogeneous with respect to their size and charge properties have been isolated.", "contents": "Fractionation of horseradish peroxidase by preparative isoelectric focusing, gel chromatography and ion-exchange chromatography. Horseradish peroxidase has been fractionated by preparative isoelectric focusing in a density gradient and in a layer of granulated gel using pH-3-10 and narrow-pH-range carrier ampholytes at different total enzyme loads. The resolution of peroxidase isoenzymes in preparative-layer isoelectric focusing was comparable to that obtained by analytical thin-layer isoelectric focusing. Isoelectrically homogeneous isoenzymes could be isolated with good recovery in a single fractionation step. Despite the excellent separation of the individual isoenzymes by isoelectric focusing in gel layers, an effective purification, indicated by the absorbance ratio A403mn/A278nm, could not be achieved by focusing applied as a single step. By different fractionation sequences combining gel chromatography, ion-exchange chromatography, and isoelectric focusing, individual isoenzymes with a high purity and homogeneous with respect to their size and charge properties have been isolated."}
{"id": "PMID:240684", "title": "N-acetylglutamate 5-phosphotransferase of Pseudomonas aeruginosa. Catalytic and regulatory properties.", "content": "Some kinetic properties of N-acetylglutamate 5-phosphotransferase (ATP: N-acetyl-L-glutamate 5-phosphotransferase EC 2.7.2.8) purified approx. 2000-fold from Pseudomonas aeruginosa have been studied. The enzyme required Mg2+ for activity. Mn2+, Zn2+, Co2+, and Ca2+, in this order, could replace Mg2+ partially. The substrate specificity was narrow: N-carbamoyl-L-glutamate and N-formyl-L-glutamate were phosphorylated, but at a lower rate than N-acetyl-L-glutamate; N-propionyl-L-glutamate was almost inactive as a substrate. dATP, but neither GTP nor ITP, could be used instead of ATP. The enzyme had a broad pH optimum from pH 6.5 to 9. Feedback inhibition by L-arginine was markedly dependent on pH. Above pH 9 no inhibition was observed. L-Citrulline was three times less potent an inhibitor than L-arginine. The enzyme showed Michaelis-Menten kinetics, even at low concentration of the second substrate. The apparent Km was 2 mM for N-acetyl-L-glutamate (at 10 mM ATP) and approx. 3 mM for ATP (at 40 mM N-acetyl-L-glutamate). In the presence of L-arginine the rate-concentration curves for N-acetyl-L-glutamate became signoidal, while no cooperativity was detected for ATP. A method was developed allowing the determination of N-acetyl-L-glutamate in the nanomolar range by means of purified enzyme.", "contents": "N-acetylglutamate 5-phosphotransferase of Pseudomonas aeruginosa. Catalytic and regulatory properties. Some kinetic properties of N-acetylglutamate 5-phosphotransferase (ATP: N-acetyl-L-glutamate 5-phosphotransferase EC 2.7.2.8) purified approx. 2000-fold from Pseudomonas aeruginosa have been studied. The enzyme required Mg2+ for activity. Mn2+, Zn2+, Co2+, and Ca2+, in this order, could replace Mg2+ partially. The substrate specificity was narrow: N-carbamoyl-L-glutamate and N-formyl-L-glutamate were phosphorylated, but at a lower rate than N-acetyl-L-glutamate; N-propionyl-L-glutamate was almost inactive as a substrate. dATP, but neither GTP nor ITP, could be used instead of ATP. The enzyme had a broad pH optimum from pH 6.5 to 9. Feedback inhibition by L-arginine was markedly dependent on pH. Above pH 9 no inhibition was observed. L-Citrulline was three times less potent an inhibitor than L-arginine. The enzyme showed Michaelis-Menten kinetics, even at low concentration of the second substrate. The apparent Km was 2 mM for N-acetyl-L-glutamate (at 10 mM ATP) and approx. 3 mM for ATP (at 40 mM N-acetyl-L-glutamate). In the presence of L-arginine the rate-concentration curves for N-acetyl-L-glutamate became signoidal, while no cooperativity was detected for ATP. A method was developed allowing the determination of N-acetyl-L-glutamate in the nanomolar range by means of purified enzyme."}
{"id": "PMID:240685", "title": "The stimulation of liver phosphorylase b by AMP, fluoride and sulfate. A technical note on the specific determination of the a and b forms of liver glycogen phosphorylase.", "content": "1. The activity of liver phosphorylase b from several mammalian species has been studied. The enzyme from rat or mouse has a higher activity than the rabbit enzyme, which is itself more active than pig liver phosphorylase b. 2 The activity of liver phosphorylase b is influenced by anions and by AMP, and these effects are influenced by pH. Fluoride, which is currently added to the assay mixture of phosphorylase a in crude preparations, is about as active as sulfate as a stimulator of phosphorylase b. 3. When assayed at pH 6.1 and in the presence of 0.15 M NaF, the activity of rat liver phosphorylase b reaches 25% of that of the a enzyme; if 1 mM AMP is also present, this value rises to 50%. 4. Methods are described that allow the determination of liver phosphorylase a without interference of b, and the determination of total phosphorylase (a+b) in rat liver.", "contents": "The stimulation of liver phosphorylase b by AMP, fluoride and sulfate. A technical note on the specific determination of the a and b forms of liver glycogen phosphorylase. 1. The activity of liver phosphorylase b from several mammalian species has been studied. The enzyme from rat or mouse has a higher activity than the rabbit enzyme, which is itself more active than pig liver phosphorylase b. 2 The activity of liver phosphorylase b is influenced by anions and by AMP, and these effects are influenced by pH. Fluoride, which is currently added to the assay mixture of phosphorylase a in crude preparations, is about as active as sulfate as a stimulator of phosphorylase b. 3. When assayed at pH 6.1 and in the presence of 0.15 M NaF, the activity of rat liver phosphorylase b reaches 25% of that of the a enzyme; if 1 mM AMP is also present, this value rises to 50%. 4. Methods are described that allow the determination of liver phosphorylase a without interference of b, and the determination of total phosphorylase (a+b) in rat liver."}
{"id": "PMID:240686", "title": "Acetyl-coenzyme-A carboxylase in cultured hepatocytes. Effects of exogenous fatty acids on the content, synthesis and degradation of the enzyme.", "content": "Studies were made on the content, synthesis and degradation of acetyl-coenzyme-A carboxylase in JTC-25 - P3 cells, hepatocytes which can be maintained in a protein-free and lipid-free chemically defined medium. The addition of corn oil or fatty acid to the medium resulted in a decrease in the activity level of the enzyme without impairing the viability of cells. All the fatty acids tested exhibited this effect, although linoleic acid and oleic acid were more effective than palmitic acid, stearic acid and arachidonic acid. Immunochemical titration and Ouchterlony double-diffusion analysis indicated that the decrease in the activity level of the enzyme observed in cells incubated in medium supplemented with fatty acid can be ascribed to a reduction of the quantity of the enzyme. Isotopic leucine incorporation studies with the use of immunochemical techniques demonstrated that this reduction of the enzyme content is due to a decrease in the rate of synthesis of the enzyme. The rate of degradation of the enzyme was essentially unaffected, the half-life being 25 and 28 h, respectively, in cells incubated in the presence and absence of fatty acid. It was shown that most of the isotopic fatty acid added to the medium was incorporated into cellular phospholipids, while a very small portion of it was recovered in triglyceride and nonesterified fatty acid.", "contents": "Acetyl-coenzyme-A carboxylase in cultured hepatocytes. Effects of exogenous fatty acids on the content, synthesis and degradation of the enzyme. Studies were made on the content, synthesis and degradation of acetyl-coenzyme-A carboxylase in JTC-25 - P3 cells, hepatocytes which can be maintained in a protein-free and lipid-free chemically defined medium. The addition of corn oil or fatty acid to the medium resulted in a decrease in the activity level of the enzyme without impairing the viability of cells. All the fatty acids tested exhibited this effect, although linoleic acid and oleic acid were more effective than palmitic acid, stearic acid and arachidonic acid. Immunochemical titration and Ouchterlony double-diffusion analysis indicated that the decrease in the activity level of the enzyme observed in cells incubated in medium supplemented with fatty acid can be ascribed to a reduction of the quantity of the enzyme. Isotopic leucine incorporation studies with the use of immunochemical techniques demonstrated that this reduction of the enzyme content is due to a decrease in the rate of synthesis of the enzyme. The rate of degradation of the enzyme was essentially unaffected, the half-life being 25 and 28 h, respectively, in cells incubated in the presence and absence of fatty acid. It was shown that most of the isotopic fatty acid added to the medium was incorporated into cellular phospholipids, while a very small portion of it was recovered in triglyceride and nonesterified fatty acid."}
{"id": "PMID:240687", "title": "Spectroscopic evidence for the formation of a 4-keto intermediate in the UDP-apiose/UDP-xylose synthase reaction.", "content": "Uridine diphospho-D-glucose (UDP-Glc) and UDP-methyl-D-glucuronate (UDP-GlcUAMe) have been shown to be competitive inhibitors for the UDP-apiose/udp-xylose synthase from cell suspension cultures of parsley. The apparent Ki values for these substrate analogues were of the same order of magnitude as the apparent Km value for the substrate UDP-D-glucuronic acid (UDP-GlcUA). The difference spectrum of the incubation mixture containing UDP-GlcUA, NAD+ and the highly purified enzyme showed a transient absorption with a maximum at 292 nm which disappeared upon addition of sodium hydroxide. The incubation with UDP-Glc or UDP-GlcUAMe also showed and NAD+-dependent absorption at 292 nm. However, in these cases a strong enhancement of the absorption at alkaline pH and a shift of the absorption maximum to longer wavelength were observed. Upon addition of 0-phenylenediamine to the enzyme incubation with UDP-Glc or UDP-GlcUAe a strong absorption with a maximum at respectively 335 and 315 nm appeared. The results show the transient formation of a 4-keto derivatives in the synthase reaction with the normal substrate UDP-GlcUA. The substrate analogues UDP-Glc and UDP-GlcUAMe can also be oxidized at C-4 by the enzyme in the presence of NAD+ to stable 4-keto derivatives which give rise to a strong absorption at alkaline pH or after reaction with o-phenylenediamine.", "contents": "Spectroscopic evidence for the formation of a 4-keto intermediate in the UDP-apiose/UDP-xylose synthase reaction. Uridine diphospho-D-glucose (UDP-Glc) and UDP-methyl-D-glucuronate (UDP-GlcUAMe) have been shown to be competitive inhibitors for the UDP-apiose/udp-xylose synthase from cell suspension cultures of parsley. The apparent Ki values for these substrate analogues were of the same order of magnitude as the apparent Km value for the substrate UDP-D-glucuronic acid (UDP-GlcUA). The difference spectrum of the incubation mixture containing UDP-GlcUA, NAD+ and the highly purified enzyme showed a transient absorption with a maximum at 292 nm which disappeared upon addition of sodium hydroxide. The incubation with UDP-Glc or UDP-GlcUAMe also showed and NAD+-dependent absorption at 292 nm. However, in these cases a strong enhancement of the absorption at alkaline pH and a shift of the absorption maximum to longer wavelength were observed. Upon addition of 0-phenylenediamine to the enzyme incubation with UDP-Glc or UDP-GlcUAe a strong absorption with a maximum at respectively 335 and 315 nm appeared. The results show the transient formation of a 4-keto derivatives in the synthase reaction with the normal substrate UDP-GlcUA. The substrate analogues UDP-Glc and UDP-GlcUAMe can also be oxidized at C-4 by the enzyme in the presence of NAD+ to stable 4-keto derivatives which give rise to a strong absorption at alkaline pH or after reaction with o-phenylenediamine."}
{"id": "PMID:240688", "title": "On the interaction of esters and peptides with carboxypeptidase B.", "content": "The specificity of porcine carboxypeptidase B towards basic and non-basic substrates was studied by employing several esters of phenyllactate. The structure of these depsipeptides complement exactly those of the corresponding phenylalanyl oligopeptide substrates. These non-basic ester-peptide pairs as well as the basic ester-peptide pair of arginyl derivatives, permits the direct comparison of the pH dependencies of the kinetic constants for the hydrolysis of those substrates by carboxypeptidase B. The data is interpreted in terms of three specific ionizing groups located at the active site of the enzyme. The mode and extent of inhibition of the hydrolysis of a specific substrate by another substrate was characterized kinetically. These results are discussed in relation to a proposed model for esterolytic and proteolytic action of carboxypeptidase B.", "contents": "On the interaction of esters and peptides with carboxypeptidase B. The specificity of porcine carboxypeptidase B towards basic and non-basic substrates was studied by employing several esters of phenyllactate. The structure of these depsipeptides complement exactly those of the corresponding phenylalanyl oligopeptide substrates. These non-basic ester-peptide pairs as well as the basic ester-peptide pair of arginyl derivatives, permits the direct comparison of the pH dependencies of the kinetic constants for the hydrolysis of those substrates by carboxypeptidase B. The data is interpreted in terms of three specific ionizing groups located at the active site of the enzyme. The mode and extent of inhibition of the hydrolysis of a specific substrate by another substrate was characterized kinetically. These results are discussed in relation to a proposed model for esterolytic and proteolytic action of carboxypeptidase B."}
{"id": "PMID:240689", "title": "The active species of 'CO2' utilized by reduced ferredoxin:CO2 oxidoreductase from Clostridium pasteurianum.", "content": "Reduced ferredoxin:CO2 oxidoreductase (CO2 reductase) from Clostridium pasteurianum catalyzes the reduction of 'CO2' to formate with reduced ferredoxin, an isotopic exchange between 'CO2' and formate in the absence of ferredoxin, and the oxidation of formate to 'CO2' with oxidized ferredoxin. The active species of 'CO2', i.e. CO2 or HCO3 (H2CO3), utilized by the enzyme was determined. The method employed for the species identification was that of Copper et al. (1968). Both 'CO2' reduction to formate and the exchange reaction were studied. Data were obtained which are compatible with those expected if CO2 is the active species. The V and the dissociation constant Ks of the enzyme - CO2 complex in dependence of pH were determined from initial velocity studies of the exchange reaction. V was found to be only slightly affected by pH between 5.5 and 7.5. Ks was markedly dependent on pH; the constant increased with decreasing pH from 0.2 mM at pH 7.5 to 3 mM at pH 5.5.", "contents": "The active species of 'CO2' utilized by reduced ferredoxin:CO2 oxidoreductase from Clostridium pasteurianum. Reduced ferredoxin:CO2 oxidoreductase (CO2 reductase) from Clostridium pasteurianum catalyzes the reduction of 'CO2' to formate with reduced ferredoxin, an isotopic exchange between 'CO2' and formate in the absence of ferredoxin, and the oxidation of formate to 'CO2' with oxidized ferredoxin. The active species of 'CO2', i.e. CO2 or HCO3 (H2CO3), utilized by the enzyme was determined. The method employed for the species identification was that of Copper et al. (1968). Both 'CO2' reduction to formate and the exchange reaction were studied. Data were obtained which are compatible with those expected if CO2 is the active species. The V and the dissociation constant Ks of the enzyme - CO2 complex in dependence of pH were determined from initial velocity studies of the exchange reaction. V was found to be only slightly affected by pH between 5.5 and 7.5. Ks was markedly dependent on pH; the constant increased with decreasing pH from 0.2 mM at pH 7.5 to 3 mM at pH 5.5."}
{"id": "PMID:240690", "title": "Change of cytochrome c structure during development of the mouse.", "content": "The structure of cytochrome c during mouse development is investigated. For this purpose the amino acid sequence of cytochrome c of the adult mouse had to be determined. The structure of cytochrome c of adult differentiated mouse cells differs in two amino acid residues from the known amino acid sequence of rabbit cytochrome c. No indication of different forms of cytochrome c in the adult differentiated cells was obtained. The structure of cytochrome c from 11.5-day-old mouse embryos is identical with that of adult mouse tissues. Since germ cells after meiotic division are the immediate precursors of a new individual, the structure of cytochrome c from sperm-containing mice testes was investigated. By means of chromatography of the cytochrome c and of peptide maps and amino acid analyses of its tryptic peptides, it is shown that mouse testis contains two isocytochromes c in about equal amount. The structure of one of these two isocytochromes c is identical with the structure of the adult-type cytochrome c of mouse. The testis-specific cytochrome c, which is assumed to be located in the sperm cells, differs in 13 of its 104 amino acid residues from the adult-type cytochrome c. From comparison of the primary and the spatial structures of the adult-type and the sperm-type isocytochromes c with the known structures of cytochrome c of more than 65 different species it is concluded that the duplication of the cytochrome c structural gene, causing the existence of the two ontogenetic-specific isocytochromes c in mouse, has occurred early in the evolution of eucaryotes.", "contents": "Change of cytochrome c structure during development of the mouse. The structure of cytochrome c during mouse development is investigated. For this purpose the amino acid sequence of cytochrome c of the adult mouse had to be determined. The structure of cytochrome c of adult differentiated mouse cells differs in two amino acid residues from the known amino acid sequence of rabbit cytochrome c. No indication of different forms of cytochrome c in the adult differentiated cells was obtained. The structure of cytochrome c from 11.5-day-old mouse embryos is identical with that of adult mouse tissues. Since germ cells after meiotic division are the immediate precursors of a new individual, the structure of cytochrome c from sperm-containing mice testes was investigated. By means of chromatography of the cytochrome c and of peptide maps and amino acid analyses of its tryptic peptides, it is shown that mouse testis contains two isocytochromes c in about equal amount. The structure of one of these two isocytochromes c is identical with the structure of the adult-type cytochrome c of mouse. The testis-specific cytochrome c, which is assumed to be located in the sperm cells, differs in 13 of its 104 amino acid residues from the adult-type cytochrome c. From comparison of the primary and the spatial structures of the adult-type and the sperm-type isocytochromes c with the known structures of cytochrome c of more than 65 different species it is concluded that the duplication of the cytochrome c structural gene, causing the existence of the two ontogenetic-specific isocytochromes c in mouse, has occurred early in the evolution of eucaryotes."}
{"id": "PMID:240691", "title": "Association of glyceraldehyde-3-phosphate dehydrogenase with the particulate fraction of chicken skeletal muscle.", "content": "When chicken breast muscle was homogenized in water, approximately 86% of the glyceraldehyde-3-phosphate dehydrogenase was associated with the particulate fraction. The enzyme was solubilized by increasing pH with a very marked increase in the pH range of 6.9 to 7.1. At low ionic strength (about 0.015), approximately 50% of the enzyme is solubilized at pH 7.5 and above. Increasing ionic strength also led to increased solubilization. In addition, there was a specific cation effect with Ca2+ greater than Mg2+ greater than K+ greater than Na+ at a constant ionic strength. Glyceraldehyde 3-phosphate and 2,3-bisphosphoglycerate were effective in partially solubilizing the enzyme. Solubilized glyceraldehyde-3-phosphate dehydrogenase can rebind to the particulate fraction of the homogenized muscle. The soluble form of the enzyme has a higher V and a higher Km (glyceraldehyde-3-phosphate) than the enzyme bound to the particulate fraction.", "contents": "Association of glyceraldehyde-3-phosphate dehydrogenase with the particulate fraction of chicken skeletal muscle. When chicken breast muscle was homogenized in water, approximately 86% of the glyceraldehyde-3-phosphate dehydrogenase was associated with the particulate fraction. The enzyme was solubilized by increasing pH with a very marked increase in the pH range of 6.9 to 7.1. At low ionic strength (about 0.015), approximately 50% of the enzyme is solubilized at pH 7.5 and above. Increasing ionic strength also led to increased solubilization. In addition, there was a specific cation effect with Ca2+ greater than Mg2+ greater than K+ greater than Na+ at a constant ionic strength. Glyceraldehyde 3-phosphate and 2,3-bisphosphoglycerate were effective in partially solubilizing the enzyme. Solubilized glyceraldehyde-3-phosphate dehydrogenase can rebind to the particulate fraction of the homogenized muscle. The soluble form of the enzyme has a higher V and a higher Km (glyceraldehyde-3-phosphate) than the enzyme bound to the particulate fraction."}
{"id": "PMID:240692", "title": "Affinity chromatography on immobilised nucleotides. Some applications to the purification of thermophilic dehydrogenases and kinases.", "content": "The effect of pH and temperature on the capacity and binding of Bacillus stearothermophilus, alcohol dehydrogenase and phosphofructokinase to N6-(6-aminohexyl)-5'-AMP-Sepharose has been examined. Specific elution from the substituted AMP-Sepharose was examined using a variety of cofactors, fragments of cofactors and substrates. A purification scheme for each enzyme on the substituted AMP-Sepharose using nucleotides and gradients of pH and salt is presented. Interestingly, elevated temperature increased the affinity of both enzymes for N6-(6-aminohexyl)-5'-AMP-Sepharose, however, the Michaelis constant for nucleotide determined at various temperatures remained constant. The effect of pH and salt concentration on the binding of B. stearothermophilus glyceraldehyde-3-phosphate dehydrogenase to 6-aminohexanoyl-NAD+-Sepharose was also examined; raising the pH above 7.5 lowers the capacity of the matrix and the effect of a range of ammonium sulphate concentrations on the adsorption of the enzyme was examined. A specific purification of glyceraldehyde-3-phosphate dehydrogenase from partially purified extracts of this organism was achieved.", "contents": "Affinity chromatography on immobilised nucleotides. Some applications to the purification of thermophilic dehydrogenases and kinases. The effect of pH and temperature on the capacity and binding of Bacillus stearothermophilus, alcohol dehydrogenase and phosphofructokinase to N6-(6-aminohexyl)-5'-AMP-Sepharose has been examined. Specific elution from the substituted AMP-Sepharose was examined using a variety of cofactors, fragments of cofactors and substrates. A purification scheme for each enzyme on the substituted AMP-Sepharose using nucleotides and gradients of pH and salt is presented. Interestingly, elevated temperature increased the affinity of both enzymes for N6-(6-aminohexyl)-5'-AMP-Sepharose, however, the Michaelis constant for nucleotide determined at various temperatures remained constant. The effect of pH and salt concentration on the binding of B. stearothermophilus glyceraldehyde-3-phosphate dehydrogenase to 6-aminohexanoyl-NAD+-Sepharose was also examined; raising the pH above 7.5 lowers the capacity of the matrix and the effect of a range of ammonium sulphate concentrations on the adsorption of the enzyme was examined. A specific purification of glyceraldehyde-3-phosphate dehydrogenase from partially purified extracts of this organism was achieved."}
{"id": "PMID:240693", "title": "Crystalline L-histidine ammonia-lyase of Achromobacter liquidum. Crystallization and enzymic properties.", "content": "Crystalline L-histidine ammonia-lyase of Achromobacter liquidum was prepared with a 24% recovery of the activity. The specific activity of the pure enzyme (63 mumol of urocanic acid min-1 mg-1) is similar to those so far reported for the enzyme from other sources. The purified enzyme appeared to be homogeneous by analytical disc electrophoresis and isoelectric focusing (pI = 4.95). The molecular weight determined by Sephadex G-200 gel filtration is 200000. The optimum pH is 8.2, and the optimum temperature is 50 degrees C. The enzyme showed strict specificity to L-histidine (Km = 3.6 mM). Several histidine derivatives are not susceptible to the enzyme but do inhibit the enzyme activity competitively; the most effective inhibitors are L-histidine methyl ester (Ki = 3.66 mM) and beta-imidazole lactic acid (Ki = 3.84 mM). L-Histidine  hydrazide (Ki = 36 mM) and imidazole (Ki = 6 mM) noncompetitively inhibited the enzyme EDTA markedly inhibited enzyme activity and this inhibition were reversed by divalent metal ions such as Mn2+, Co2+ Zn2+, Ni2+, Mg2+, and Ca2+. These results suggest that the presence of divalent metal ions is necessary for the catalytic activity of histidine ammonia-lyase. Sodium borohydride and hydrogen peroxide inhibited the enzyme activity.", "contents": "Crystalline L-histidine ammonia-lyase of Achromobacter liquidum. Crystallization and enzymic properties. Crystalline L-histidine ammonia-lyase of Achromobacter liquidum was prepared with a 24% recovery of the activity. The specific activity of the pure enzyme (63 mumol of urocanic acid min-1 mg-1) is similar to those so far reported for the enzyme from other sources. The purified enzyme appeared to be homogeneous by analytical disc electrophoresis and isoelectric focusing (pI = 4.95). The molecular weight determined by Sephadex G-200 gel filtration is 200000. The optimum pH is 8.2, and the optimum temperature is 50 degrees C. The enzyme showed strict specificity to L-histidine (Km = 3.6 mM). Several histidine derivatives are not susceptible to the enzyme but do inhibit the enzyme activity competitively; the most effective inhibitors are L-histidine methyl ester (Ki = 3.66 mM) and beta-imidazole lactic acid (Ki = 3.84 mM). L-Histidine  hydrazide (Ki = 36 mM) and imidazole (Ki = 6 mM) noncompetitively inhibited the enzyme EDTA markedly inhibited enzyme activity and this inhibition were reversed by divalent metal ions such as Mn2+, Co2+ Zn2+, Ni2+, Mg2+, and Ca2+. These results suggest that the presence of divalent metal ions is necessary for the catalytic activity of histidine ammonia-lyase. Sodium borohydride and hydrogen peroxide inhibited the enzyme activity."}
{"id": "PMID:240694", "title": "D-alanine carboxypeptidase activity of Micrococcus lysodeikticus released into the protoplasting medium.", "content": "Conversion of whole cells of Micrococcus lysodeikticus to protoplasts allowed the release of a soluble form of a D-alanine carboxypeptidase into the protoplasting medium. The enzyme cleaves the terminal D-alanine from the radioactively labelled UDP-N-acetylmuramyl-pentapeptide containing L-lysine as the diamino acid. However, the enzyme is only minimally active in this fraction so that it had to be enriched and partially purified before its properties could be studied. Chromatography on carboxymethyl-Sephadex removed the lysozyme used in the protoplasting of the cells. The material which was unadsorbed to the column was applied to an affinity chromatography column of Ampicillin-Sepharose. Most of the contaminating protein was washed from the column while the D-alanine carboxypeptidase adhered to the resin and could be eluted with 0.5 M Tris-HCl buffer pH 8.6. Some of the properties of the enzymic activity were studied using this preparation. The enzyme was activated by Mg2+ ions with a broad optimum from 15--35 mM. It was maximally active when NaCl at a concentrations of 0.06--0.08 M was added to the assay, and the pH curve was biphasic with an alkaline optimum. The Km for substrate was found to be 0.118 mM. Enzymic activity was completely inhibited by low concentrations of Ampicillin and penicillin G.", "contents": "D-alanine carboxypeptidase activity of Micrococcus lysodeikticus released into the protoplasting medium. Conversion of whole cells of Micrococcus lysodeikticus to protoplasts allowed the release of a soluble form of a D-alanine carboxypeptidase into the protoplasting medium. The enzyme cleaves the terminal D-alanine from the radioactively labelled UDP-N-acetylmuramyl-pentapeptide containing L-lysine as the diamino acid. However, the enzyme is only minimally active in this fraction so that it had to be enriched and partially purified before its properties could be studied. Chromatography on carboxymethyl-Sephadex removed the lysozyme used in the protoplasting of the cells. The material which was unadsorbed to the column was applied to an affinity chromatography column of Ampicillin-Sepharose. Most of the contaminating protein was washed from the column while the D-alanine carboxypeptidase adhered to the resin and could be eluted with 0.5 M Tris-HCl buffer pH 8.6. Some of the properties of the enzymic activity were studied using this preparation. The enzyme was activated by Mg2+ ions with a broad optimum from 15--35 mM. It was maximally active when NaCl at a concentrations of 0.06--0.08 M was added to the assay, and the pH curve was biphasic with an alkaline optimum. The Km for substrate was found to be 0.118 mM. Enzymic activity was completely inhibited by low concentrations of Ampicillin and penicillin G."}
{"id": "PMID:240695", "title": "Protein kinase of bacteriophage T7. 2. Properties, enzyme synthesis in vitro and regulation of enzyme synthesis and activity in vivo.", "content": "Protein kinase, which was isolated from cells infected with T7, is indeed a viral gene product. This is shown by DNA-dependent synthesis in vitro. The protein kinase transfers phosphate from ATP to seryl or threonyl residues in protein. The enzyme has only a relative requirement for magnesium ions, but is only active at low ionic strength. The best substrate is lysozyme. T7 protein kinase activity is not stimulated by cyclic 3':5'-AMP and/or cyclic 3':5'-GMP. The T7 protein kinase carries -- SH groups essential for activity. There is indication that the enzyme phosphorylates itself and causes self inactivation, which may explain the fast disappearance of enzyme activity in vivo. Bacteriophage T3 also induces a protein kinase which is similar to the T7-induced enzyme in all respects tested.", "contents": "Protein kinase of bacteriophage T7. 2. Properties, enzyme synthesis in vitro and regulation of enzyme synthesis and activity in vivo. Protein kinase, which was isolated from cells infected with T7, is indeed a viral gene product. This is shown by DNA-dependent synthesis in vitro. The protein kinase transfers phosphate from ATP to seryl or threonyl residues in protein. The enzyme has only a relative requirement for magnesium ions, but is only active at low ionic strength. The best substrate is lysozyme. T7 protein kinase activity is not stimulated by cyclic 3':5'-AMP and/or cyclic 3':5'-GMP. The T7 protein kinase carries -- SH groups essential for activity. There is indication that the enzyme phosphorylates itself and causes self inactivation, which may explain the fast disappearance of enzyme activity in vivo. Bacteriophage T3 also induces a protein kinase which is similar to the T7-induced enzyme in all respects tested."}
{"id": "PMID:240696", "title": "A pathway of chitosan formation in Mucor rouxii. Enzymatic deacetylation of chitin.", "content": "1. An enzyme that catalyzes hydrolysis of acetamido groups of chitin derivatives was found in the supernatant fraction of Mucor rouxii. 2. Partially O-hydroxyethylated chitin (glycol chitin) was used as a substrate in the purification and characterization of this enzyme. A 140-fold purification was obtained by means of ammonium sulfate fractionation followed by chromatography on carboxymethylcellulose and DEAE-cellulose. 3. The enzyme releases about 30% of the acetyl groups of glycol chitin, giving a product with a decreased sensitivity to lysozyme. The enzyme also deacetylates chitin and N-acetylchitooligoses, whereas it is inactive toward bacterial cell wall peptidoglycan, N-acetylated heparin, a polymer of N-acetylgalactosamine, di-N-acetylchitobiose and monomeric N-acetylglucosamine derivatives. 4. This enzyme shows a pH optimum of 5.5. The Km value for glycol chitin is 0.87 g/l or 2.6 mM with respect to monosaccharide residues. 5. The occurrence of this enzyme accounts for the formation of chitosan in fungi.", "contents": "A pathway of chitosan formation in Mucor rouxii. Enzymatic deacetylation of chitin. 1. An enzyme that catalyzes hydrolysis of acetamido groups of chitin derivatives was found in the supernatant fraction of Mucor rouxii. 2. Partially O-hydroxyethylated chitin (glycol chitin) was used as a substrate in the purification and characterization of this enzyme. A 140-fold purification was obtained by means of ammonium sulfate fractionation followed by chromatography on carboxymethylcellulose and DEAE-cellulose. 3. The enzyme releases about 30% of the acetyl groups of glycol chitin, giving a product with a decreased sensitivity to lysozyme. The enzyme also deacetylates chitin and N-acetylchitooligoses, whereas it is inactive toward bacterial cell wall peptidoglycan, N-acetylated heparin, a polymer of N-acetylgalactosamine, di-N-acetylchitobiose and monomeric N-acetylglucosamine derivatives. 4. This enzyme shows a pH optimum of 5.5. The Km value for glycol chitin is 0.87 g/l or 2.6 mM with respect to monosaccharide residues. 5. The occurrence of this enzyme accounts for the formation of chitosan in fungi."}
{"id": "PMID:240697", "title": "Amino-acid sequence of the peptide segment liberated during activation of prochymosin (prorennin).", "content": "By conversion of prochymosin into active chymosin and N-terminal segment of 42 amino acid residues is liberated. In one activation experiment this segment was recovered in two peptides; in a second experiment the activation segment was cleaved into three peptides. The primary structures of the peptides have been determined. Overlaps between these peptides and between the activation segment and the active enzyme have been obtained from peptides produced by tryptic digestion of denatured prochymosin. Comparison of the amino acid sequences of the activation segments from bovine prochymosin, bovine pepsinogen and porcine pepsinogen shows considerable homology.", "contents": "Amino-acid sequence of the peptide segment liberated during activation of prochymosin (prorennin). By conversion of prochymosin into active chymosin and N-terminal segment of 42 amino acid residues is liberated. In one activation experiment this segment was recovered in two peptides; in a second experiment the activation segment was cleaved into three peptides. The primary structures of the peptides have been determined. Overlaps between these peptides and between the activation segment and the active enzyme have been obtained from peptides produced by tryptic digestion of denatured prochymosin. Comparison of the amino acid sequences of the activation segments from bovine prochymosin, bovine pepsinogen and porcine pepsinogen shows considerable homology."}
{"id": "PMID:240698", "title": "Solubilization and characterization of phosphoprotein phosphatase(s) from bovine corpus-luteum plasma membranes.", "content": "Plasma membrane fractions I and II isolated from bovine corpus luteum contain phosphoprotein phosphatases. Enzyme activities associated with both membrane fractions showed pH optima in the neutral range and were most active with phosphoprotamine as the exogenous substrate. The enzyme activity was partially inhibited by Co2+, Zn2+ and Fe2+. Dithioerythritol, glutathione (reduced) and 2-mercaptoethanol stimulated the enzyme activity, whereas N-ethylmaleimide and N-phenylmaleimide were inhibitory. Similarly, various cyclic nucleotides and nuclsoside triphosphates also inhibited phosphoprotein phosphatase activities. The phosphatase activity was also observed with endogenous phosphorylated membrane proteins as substrate. The endogenous phosphorylation of membranes was rapid and attained a maximal level after 15--20 min of incubation. Initially endogenous dephosphorylation was also very rapid, but did not reach completion. In addition to phosphoprotein phosphatase, membrane preparations also possessed very active cyclic-AMP-dependent protein kinase activity. Phosphoprotein phosphatase activity from plasma membranes was solubilized by ionic and nonionic detergents. Optimal solubilization was achieved with 0.1% sodium deoxycholate. Sucrose density gradient centrifugation of deoxycholate-solubilized fraction I and fraction II membranes resolved phosphoprotein phosphatase activity into two species with apparent sedimentation coefficients of 6.7 S (Mr 130000) and 4.8 S (Mr 90000). Cyclic-AMPstimulated protein kinase activity sedimented as a broad peak with a sedimentation coefficient of 5.5 S (Mr 110000).", "contents": "Solubilization and characterization of phosphoprotein phosphatase(s) from bovine corpus-luteum plasma membranes. Plasma membrane fractions I and II isolated from bovine corpus luteum contain phosphoprotein phosphatases. Enzyme activities associated with both membrane fractions showed pH optima in the neutral range and were most active with phosphoprotamine as the exogenous substrate. The enzyme activity was partially inhibited by Co2+, Zn2+ and Fe2+. Dithioerythritol, glutathione (reduced) and 2-mercaptoethanol stimulated the enzyme activity, whereas N-ethylmaleimide and N-phenylmaleimide were inhibitory. Similarly, various cyclic nucleotides and nuclsoside triphosphates also inhibited phosphoprotein phosphatase activities. The phosphatase activity was also observed with endogenous phosphorylated membrane proteins as substrate. The endogenous phosphorylation of membranes was rapid and attained a maximal level after 15--20 min of incubation. Initially endogenous dephosphorylation was also very rapid, but did not reach completion. In addition to phosphoprotein phosphatase, membrane preparations also possessed very active cyclic-AMP-dependent protein kinase activity. Phosphoprotein phosphatase activity from plasma membranes was solubilized by ionic and nonionic detergents. Optimal solubilization was achieved with 0.1% sodium deoxycholate. Sucrose density gradient centrifugation of deoxycholate-solubilized fraction I and fraction II membranes resolved phosphoprotein phosphatase activity into two species with apparent sedimentation coefficients of 6.7 S (Mr 130000) and 4.8 S (Mr 90000). Cyclic-AMPstimulated protein kinase activity sedimented as a broad peak with a sedimentation coefficient of 5.5 S (Mr 110000)."}
{"id": "PMID:240699", "title": "A kinetic study of mitochondrial calcium transport.", "content": "This report describes a kinetic analysis of energy-linked Ca2+ transport in rat liver mitochondria, in which a ruthenium red/EGTA [ethanedioxy-bis(ethylamine)-tetraacetic acid] quenching technique has been used to measure rates of 45Ca2+ transport. Accurately known concentrations of free 45Ca2+ were generated with Ca2+/nitrilotriacetic acids buffers for the determination of substrate/velocity relationships. The results show that the initial velocity of transport is a sigmoidal function of Ca2+ concentration (Hill coefficient = 1.7), the Km being 4 muM Ca4 at 0 degrees C and pH 7.4. These values for the Hill coefficient and the Km remain constant in the presence of up to 2 mM phosphate, but with 10 mM acetate both parameters are increased slightly. Both permeant acids increase the maximum velocity to an extent dependent on their concentration. The Ca2+-binding site(s) of the carrier contains a group ionizing at pH approximately 7.5 at 0 degrees C, which is functional in the dissociated state. The stimulatory effect of permeant acids is ascribed to their facilitating the release of Ca2+ from the carrier to the internal phase, an interpretation which is strengthened by the lack of effect of the permeant anion SCN- on Ca2+ transport. Studies on the time-course of Ca2+ uptake and of EFTA-induced Ca2+ efflux from pre-loaded mitochondria demonstrate the reversibility of the carrier in respiring mitochondria and the extent to which this property is influenced by permeant acids. These data are accommodated in a carrier mechanism based on electrophoretic transport of Ca2+ bound to pairs of interacting acidic sites.", "contents": "A kinetic study of mitochondrial calcium transport. This report describes a kinetic analysis of energy-linked Ca2+ transport in rat liver mitochondria, in which a ruthenium red/EGTA [ethanedioxy-bis(ethylamine)-tetraacetic acid] quenching technique has been used to measure rates of 45Ca2+ transport. Accurately known concentrations of free 45Ca2+ were generated with Ca2+/nitrilotriacetic acids buffers for the determination of substrate/velocity relationships. The results show that the initial velocity of transport is a sigmoidal function of Ca2+ concentration (Hill coefficient = 1.7), the Km being 4 muM Ca4 at 0 degrees C and pH 7.4. These values for the Hill coefficient and the Km remain constant in the presence of up to 2 mM phosphate, but with 10 mM acetate both parameters are increased slightly. Both permeant acids increase the maximum velocity to an extent dependent on their concentration. The Ca2+-binding site(s) of the carrier contains a group ionizing at pH approximately 7.5 at 0 degrees C, which is functional in the dissociated state. The stimulatory effect of permeant acids is ascribed to their facilitating the release of Ca2+ from the carrier to the internal phase, an interpretation which is strengthened by the lack of effect of the permeant anion SCN- on Ca2+ transport. Studies on the time-course of Ca2+ uptake and of EFTA-induced Ca2+ efflux from pre-loaded mitochondria demonstrate the reversibility of the carrier in respiring mitochondria and the extent to which this property is influenced by permeant acids. These data are accommodated in a carrier mechanism based on electrophoretic transport of Ca2+ bound to pairs of interacting acidic sites."}
{"id": "PMID:240700", "title": "Induction potential for glyoxylate cycle enzymes during the cell cycle of Euglena gracilis.", "content": "In light/dark synchronized cultures of Euglena gracilis Klebs Z the enzymes malate synthase, isocitrate lyase and acetate thiokinase were induced upon addition of acetate at all stages of the cell cycle. Cycloheximide and p-fluorophenylalanine inhibited the development of enzyme activity, showing that induction was dependent on protein synthesis. The maximum rate of induction for all three enzymes was constant for much of the cell cycle but doubles in a single step during the period of DNA replication. Although these data indicate that enzyme potential was regulated by gene dosage and that the structural gene for each enzyme was continuously available for transcription during the cell-cycle it was not possible by using inhibitors of RNA synthesis, to demonstrate concurrent transcription during enzyme induction.", "contents": "Induction potential for glyoxylate cycle enzymes during the cell cycle of Euglena gracilis. In light/dark synchronized cultures of Euglena gracilis Klebs Z the enzymes malate synthase, isocitrate lyase and acetate thiokinase were induced upon addition of acetate at all stages of the cell cycle. Cycloheximide and p-fluorophenylalanine inhibited the development of enzyme activity, showing that induction was dependent on protein synthesis. The maximum rate of induction for all three enzymes was constant for much of the cell cycle but doubles in a single step during the period of DNA replication. Although these data indicate that enzyme potential was regulated by gene dosage and that the structural gene for each enzyme was continuously available for transcription during the cell-cycle it was not possible by using inhibitors of RNA synthesis, to demonstrate concurrent transcription during enzyme induction."}
{"id": "PMID:240701", "title": "Uptake of taurocholic acid into isolated rat-liver cells.", "content": "Binding and transport characteristics for uptake of taurocholic acid by isolated rat liver cells were studied. 1. An adsorption of taurocholate to the cell surface is terminated in less than 15 s. A Ks of 0.55 mM and a total binding capacity of 3.8 nmol/mg cell protein is determined. 2. The rate of uptake of taurocholate follows Michaelis-Menten kinetics with Km = 19 muM and V = 1.7 nmol/mg protein min. 3. There is a broad pH optimum for uptake between pH 6.5 -- 8.0. 4. The activation energy amounts to 29 kcal/mol. At high taurocholate concentration an unusual upward bend is observed in the Arrhenius plot. 5. Taurocholate uptake is competitively inhibited by taurochenodeoxycholate (Ki = 9 muM). It is noncompetitively inhibited by bromosulfophthalein (Ki = 3 muM). 6. At physiological taurocholate concentrations a 200-fold intracellular accumulation of taurocholate is observed. 7. Uptake is inhibited by about 75% by either antimycin A, carbonylcyanide m-chlorophenyl-hydrazone, ouabain. 8. Replacement of extracellular Na+ by either K+ or sucrose results in a 75% decrease of uptake. 9. It is concluded that taurocholate uptake is a carrier-mediated process, and suggested that the energy for intracellular accumulation is made available by cotransport of Na+.", "contents": "Uptake of taurocholic acid into isolated rat-liver cells. Binding and transport characteristics for uptake of taurocholic acid by isolated rat liver cells were studied. 1. An adsorption of taurocholate to the cell surface is terminated in less than 15 s. A Ks of 0.55 mM and a total binding capacity of 3.8 nmol/mg cell protein is determined. 2. The rate of uptake of taurocholate follows Michaelis-Menten kinetics with Km = 19 muM and V = 1.7 nmol/mg protein min. 3. There is a broad pH optimum for uptake between pH 6.5 -- 8.0. 4. The activation energy amounts to 29 kcal/mol. At high taurocholate concentration an unusual upward bend is observed in the Arrhenius plot. 5. Taurocholate uptake is competitively inhibited by taurochenodeoxycholate (Ki = 9 muM). It is noncompetitively inhibited by bromosulfophthalein (Ki = 3 muM). 6. At physiological taurocholate concentrations a 200-fold intracellular accumulation of taurocholate is observed. 7. Uptake is inhibited by about 75% by either antimycin A, carbonylcyanide m-chlorophenyl-hydrazone, ouabain. 8. Replacement of extracellular Na+ by either K+ or sucrose results in a 75% decrease of uptake. 9. It is concluded that taurocholate uptake is a carrier-mediated process, and suggested that the energy for intracellular accumulation is made available by cotransport of Na+."}
{"id": "PMID:240702", "title": "Purification of arginases from human-leukemic lymphocytes and granulocytes: study of their physicochemical and kinetic properties.", "content": "Arginase has been isolated from granulocytes of a patient with chronic myelocytic leukemia and from lymphocytes of a patient with chronic lymphocytic leukemia and both enzymes have been purified to apparent homogeneity. The purification procedure employed acetone extraction, ammonium sulfate precipitation, DEAE-cellulose and CM-Sephadex chromatography and gel filtration on Bio-Gel A 1.5m. Both enzymes appear to be metalloenzymes, and to have molecular weights of about 120 000. Studies with the dissociated enzymes suggest that the subunit molecular weight is about 37 000, in agreement with a tetrameric aggregate structure of the native enzymes. Human leukemic granulocyte and lymphocyte arginases are strongly basic proteins with pI values between 9.25 and 9.35. Their free -SH groups enabled them to be linked to organomercurial-agarose. The kinetic properties estimated for both enzymes showed an optimum pH of 8.5, and an optimal MnCl2 concentration of 0.01 M. The Km for L-arginine is 2.7-3.1 mM and L-ornithine exhibits a mixed type of inhibition, with a Ki of 15.5-15.7 mM.", "contents": "Purification of arginases from human-leukemic lymphocytes and granulocytes: study of their physicochemical and kinetic properties. Arginase has been isolated from granulocytes of a patient with chronic myelocytic leukemia and from lymphocytes of a patient with chronic lymphocytic leukemia and both enzymes have been purified to apparent homogeneity. The purification procedure employed acetone extraction, ammonium sulfate precipitation, DEAE-cellulose and CM-Sephadex chromatography and gel filtration on Bio-Gel A 1.5m. Both enzymes appear to be metalloenzymes, and to have molecular weights of about 120 000. Studies with the dissociated enzymes suggest that the subunit molecular weight is about 37 000, in agreement with a tetrameric aggregate structure of the native enzymes. Human leukemic granulocyte and lymphocyte arginases are strongly basic proteins with pI values between 9.25 and 9.35. Their free -SH groups enabled them to be linked to organomercurial-agarose. The kinetic properties estimated for both enzymes showed an optimum pH of 8.5, and an optimal MnCl2 concentration of 0.01 M. The Km for L-arginine is 2.7-3.1 mM and L-ornithine exhibits a mixed type of inhibition, with a Ki of 15.5-15.7 mM."}
{"id": "PMID:240703", "title": "The self-association of chicken-erythrocyte histones.", "content": "The self-association of the separate histone fractions isolated from chicken erythrocytes has been studied in solution at a number of different pH values and ionic strengths. The apparent molecular weights of the histones were determined over a range of macromolecular concentrations using the techniques of osmotic pressure and sedimentation equilibrium. Histone F2c (H5) did not associate under any of the conditions investigated whereas the other histone fractions all appeared to undergo self-association forming dimers, dimers of dimers, etc. The degree of association increased with the pH and ionic strength of the medium. The tendency to aggregate increased in the order; histone F2c (H5) (non-aggregating), histone F2b (H2B), histone F2a2 (H2A), histone F3 (H3), histone F2a1 (H4) (highly aggregating). In the case of histone F2a2 (H2A) at pH 3.0 and ionic strength 0.1, the apparent weight-average molecular weight was determined at a number of macromolecular concentrations at five different temperatures. The self-association was analysed according to the method of Adams (published by Beckman Instruments Inc. in 1967) and shown to be a monomer-dimer-tetramer equilibrium. The association constants were evaluated at each of the temperatures studied and from their variation with temperature the values of the enthalpy and entropy of association were calculated. The intermolecular association was characterised by only a small change in enthalpy but a large, positive, change in entropy. This suggests that the association of histones at acid pH is due to hydrophobic interactions between the relatively uncharged segments of like polypeptide chains.", "contents": "The self-association of chicken-erythrocyte histones. The self-association of the separate histone fractions isolated from chicken erythrocytes has been studied in solution at a number of different pH values and ionic strengths. The apparent molecular weights of the histones were determined over a range of macromolecular concentrations using the techniques of osmotic pressure and sedimentation equilibrium. Histone F2c (H5) did not associate under any of the conditions investigated whereas the other histone fractions all appeared to undergo self-association forming dimers, dimers of dimers, etc. The degree of association increased with the pH and ionic strength of the medium. The tendency to aggregate increased in the order; histone F2c (H5) (non-aggregating), histone F2b (H2B), histone F2a2 (H2A), histone F3 (H3), histone F2a1 (H4) (highly aggregating). In the case of histone F2a2 (H2A) at pH 3.0 and ionic strength 0.1, the apparent weight-average molecular weight was determined at a number of macromolecular concentrations at five different temperatures. The self-association was analysed according to the method of Adams (published by Beckman Instruments Inc. in 1967) and shown to be a monomer-dimer-tetramer equilibrium. The association constants were evaluated at each of the temperatures studied and from their variation with temperature the values of the enthalpy and entropy of association were calculated. The intermolecular association was characterised by only a small change in enthalpy but a large, positive, change in entropy. This suggests that the association of histones at acid pH is due to hydrophobic interactions between the relatively uncharged segments of like polypeptide chains."}
{"id": "PMID:240704", "title": "Metabolism of aromatic compounds by fungi. Kinetic properties and mechanism of 3-carboxy-cis,cis-muconate cyclase from Aspergillus niger.", "content": "A preliminary investigation of the kinetic properties of 3-carboxy-cis,cis-muconate cyclase (EC 5.5.1.5) has been performed. The initial velocity of the reaction was shown to be proportional to the concentration of the enzyme in the assay system adopted and the apparent Km was found to be 57 muM at pH 6.0 and 30 degrees C but at concentrations exceeding 70 muM, substrate inhibition was apparent. At pH 6.0 the Ki for the substrate was 0.45 mM. Plots of V and Km against pH showed inflexions at pH 5.3 and pH 6.4. The enzyme was inhibited by a variety of inorganic anions and by a number of dicarboxylic and tricarboxylic acids. The degree of inhibition exerted by these acids was found to be proportional to the proximity of their carboxyl groups, the cis configuration being a more effective inhibitor than the trans configuration. As inhibition was competitive in each case, the presence of an anion-sensitive substrate-binding site has been postulated. The cis-cis, cis-trans and trans-trans isomers of muconate, 3-chloromuconate and 3-carboxy-cis-trans-muconate, close analogues of natural substrate but not attacked by the enzyme, were also found to be competitive inhibitors. The variation in pKi with pH was determined in the case of cis,cis-muconate and cis-aconitate, both of which gave curves suggesting the importance of a group with a pKa of approximately 6.4 responsible for increasing the inhibition of the enzyme. Modification by ethoxyformic anhydride and the kinetics of Rose-Bengal-sensitized photo-oxidation suggested the participation of a histidine residue in the catalytic reaction. These results are discussed in the light of recent work on enzymes catalysing analogous reactions; a likely reaction mechanism has been proposed.", "contents": "Metabolism of aromatic compounds by fungi. Kinetic properties and mechanism of 3-carboxy-cis,cis-muconate cyclase from Aspergillus niger. A preliminary investigation of the kinetic properties of 3-carboxy-cis,cis-muconate cyclase (EC 5.5.1.5) has been performed. The initial velocity of the reaction was shown to be proportional to the concentration of the enzyme in the assay system adopted and the apparent Km was found to be 57 muM at pH 6.0 and 30 degrees C but at concentrations exceeding 70 muM, substrate inhibition was apparent. At pH 6.0 the Ki for the substrate was 0.45 mM. Plots of V and Km against pH showed inflexions at pH 5.3 and pH 6.4. The enzyme was inhibited by a variety of inorganic anions and by a number of dicarboxylic and tricarboxylic acids. The degree of inhibition exerted by these acids was found to be proportional to the proximity of their carboxyl groups, the cis configuration being a more effective inhibitor than the trans configuration. As inhibition was competitive in each case, the presence of an anion-sensitive substrate-binding site has been postulated. The cis-cis, cis-trans and trans-trans isomers of muconate, 3-chloromuconate and 3-carboxy-cis-trans-muconate, close analogues of natural substrate but not attacked by the enzyme, were also found to be competitive inhibitors. The variation in pKi with pH was determined in the case of cis,cis-muconate and cis-aconitate, both of which gave curves suggesting the importance of a group with a pKa of approximately 6.4 responsible for increasing the inhibition of the enzyme. Modification by ethoxyformic anhydride and the kinetics of Rose-Bengal-sensitized photo-oxidation suggested the participation of a histidine residue in the catalytic reaction. These results are discussed in the light of recent work on enzymes catalysing analogous reactions; a likely reaction mechanism has been proposed."}
{"id": "PMID:240705", "title": "Enzymic synthesis of an aromatic ring from acetate units. Partial purification and some properties of flavanone synthase from cell-suspension cultures of Petroselinum hortense.", "content": "Flavanone synthase was isolated and purified about 300-fold from fermenter-grown, light-induced cell suspension cultures of Petroselinum hortense. The enzyme catalyzed the formation of the flavanone naringenin from p-coumaroyl-CoA and malonyl-CoA. Trapping experiments with an enzyme preparation, which was free of chalcone isomerase activity, revealed that in fact the flavanone and not the isomeric chalcone was the immediate product of the synthase reaction. Thus the enzyme is not a chalcone synthase as previously assumed. No coafactors were required for flavanone synthase activity. The enzyme was strongly inhibited by the two reaction products naringenin and CoASH, by the antibiotic cerulenin, by acetyl-CoA, and by several compounds reacting with sulfhydryl groups. Optimal enzyme activity was found at pH 8.0, at 30 degrees C, and at an ionic strength of 0.1--0.3 M potassium phosphate. EDTA, Mg2+, Ca2+, or Fe2+ at concentrations of about 0.7 muM did not affect the enzyme activity. Apparent molecular weights of approx. 120 000, 50 000, and 70 000, respectively, were determined for flavanone synthase and two metabolically related enzymes, chalcone isomerase and malonyl-CoA: flavonoid glycoside malonyl transferase. The partially purified flavanone synthase efficiently catalyzed the formation of malonyl pantetheine from malonyl-CoA and pantetheine. This malonyl transferase activity, and a general similarity with the condensation steps involved in the mechanisms of fatty acid and 6-methylsalicylic acid synthesis from \"acetate units\", are the basis for a hypothetical scheme which is proposed for the sequence of reactions catalyzed by the multifunctional flavanone synthase.", "contents": "Enzymic synthesis of an aromatic ring from acetate units. Partial purification and some properties of flavanone synthase from cell-suspension cultures of Petroselinum hortense. Flavanone synthase was isolated and purified about 300-fold from fermenter-grown, light-induced cell suspension cultures of Petroselinum hortense. The enzyme catalyzed the formation of the flavanone naringenin from p-coumaroyl-CoA and malonyl-CoA. Trapping experiments with an enzyme preparation, which was free of chalcone isomerase activity, revealed that in fact the flavanone and not the isomeric chalcone was the immediate product of the synthase reaction. Thus the enzyme is not a chalcone synthase as previously assumed. No coafactors were required for flavanone synthase activity. The enzyme was strongly inhibited by the two reaction products naringenin and CoASH, by the antibiotic cerulenin, by acetyl-CoA, and by several compounds reacting with sulfhydryl groups. Optimal enzyme activity was found at pH 8.0, at 30 degrees C, and at an ionic strength of 0.1--0.3 M potassium phosphate. EDTA, Mg2+, Ca2+, or Fe2+ at concentrations of about 0.7 muM did not affect the enzyme activity. Apparent molecular weights of approx. 120 000, 50 000, and 70 000, respectively, were determined for flavanone synthase and two metabolically related enzymes, chalcone isomerase and malonyl-CoA: flavonoid glycoside malonyl transferase. The partially purified flavanone synthase efficiently catalyzed the formation of malonyl pantetheine from malonyl-CoA and pantetheine. This malonyl transferase activity, and a general similarity with the condensation steps involved in the mechanisms of fatty acid and 6-methylsalicylic acid synthesis from \"acetate units\", are the basis for a hypothetical scheme which is proposed for the sequence of reactions catalyzed by the multifunctional flavanone synthase."}
{"id": "PMID:240706", "title": "Proteolytic enzymes of Neurospora crassa. Purification and some properties of five intracellular proteinases.", "content": "Five intracellular proteolytic enzymes from Neurospora crassa were isolated and partially characterized: an acidic and an alkaline endopeptidase, one carboxypeptidase and two aminopeptidases. All these proteinases were purified from the same crude extract to homogenity by heat treatment, precipitation with ammonium sulfate, chromatography on DEAE-cellulose, CM-cellulose, DEAE-Sephadex, hydroxyapatite and by gel filtration. The acid proteinase hydrolysed acid-denatured haemoglobin at pH 3.0. The alkaline proteinase and the carboxypeptidase are serine proteinases that require a sulfhydryl group for activity. The aminopeptidases are both metallo-proteinases; one posseses broad specifity to the B-chain of oxidized insulin, the other posseses only narrow specifity and can only split the N-terminal basic amino acids of peptides.", "contents": "Proteolytic enzymes of Neurospora crassa. Purification and some properties of five intracellular proteinases. Five intracellular proteolytic enzymes from Neurospora crassa were isolated and partially characterized: an acidic and an alkaline endopeptidase, one carboxypeptidase and two aminopeptidases. All these proteinases were purified from the same crude extract to homogenity by heat treatment, precipitation with ammonium sulfate, chromatography on DEAE-cellulose, CM-cellulose, DEAE-Sephadex, hydroxyapatite and by gel filtration. The acid proteinase hydrolysed acid-denatured haemoglobin at pH 3.0. The alkaline proteinase and the carboxypeptidase are serine proteinases that require a sulfhydryl group for activity. The aminopeptidases are both metallo-proteinases; one posseses broad specifity to the B-chain of oxidized insulin, the other posseses only narrow specifity and can only split the N-terminal basic amino acids of peptides."}
{"id": "PMID:240707", "title": "Ribonucleotide reductase from Escherichia coli: demonstration of a highly active form of the enzyme.", "content": "Ribonucleotide reductase from Escherichia coli consists of two nonidentical subunits, proteins B1 and B2. The activity of the enzyme in crude extracts prepared from mechanically disrupted bacteria is very low. Enzyme activity is stimulated 5 to 10-fold by addition of an excess of either subunit. Concentrated extracts from cells lysed gently on Cellophane discs (Schaller et al.) contained 10 to 20-fold higher activity than extracts from mechanically disrupted cells. This activity was not further stimulated by either B1 or B2. The system is suitable for complementation tests for the analysis of temperature-sensitive mutants affecting the ribonucleotide reductase system. Concentrated high-speed supernatants from E. coli treated with lysozyme (Wickner et al.) also contained a high ribonucleotide reductase activity, which was stimulated slightly or not at all by addition of B1 and B2. This active form of the enzyme was unstable and could not be purified. The results suggest that the intracellular form of the enzyme consists of a tight complex of proteins B1 and B2, possibly stabilized by other intracellular structures.", "contents": "Ribonucleotide reductase from Escherichia coli: demonstration of a highly active form of the enzyme. Ribonucleotide reductase from Escherichia coli consists of two nonidentical subunits, proteins B1 and B2. The activity of the enzyme in crude extracts prepared from mechanically disrupted bacteria is very low. Enzyme activity is stimulated 5 to 10-fold by addition of an excess of either subunit. Concentrated extracts from cells lysed gently on Cellophane discs (Schaller et al.) contained 10 to 20-fold higher activity than extracts from mechanically disrupted cells. This activity was not further stimulated by either B1 or B2. The system is suitable for complementation tests for the analysis of temperature-sensitive mutants affecting the ribonucleotide reductase system. Concentrated high-speed supernatants from E. coli treated with lysozyme (Wickner et al.) also contained a high ribonucleotide reductase activity, which was stimulated slightly or not at all by addition of B1 and B2. This active form of the enzyme was unstable and could not be purified. The results suggest that the intracellular form of the enzyme consists of a tight complex of proteins B1 and B2, possibly stabilized by other intracellular structures."}
{"id": "PMID:240708", "title": "The catalytic activity and penicillin sensitivity in the liquid and frozen states of membrane-bound and detergent-solubilised transpeptidase of Streptomyces R61.", "content": "The Km, app. values of the membrane-bound transpeptidase of Streptomyces R61 for the donor Ac2-L-Lys-D-Ala-D-Ala and the acceptor Gly-Gly are not affected by temperature variations when the reaction mixtures are incubated in liquid suspensions. At -5 degrees C, the incubation can be carried out either in the liquid or in the frozen state. The enzyme is active in the latter state. In the frozen state, the Km, app. value for the acceptor remains unchanged but there is a 3-fold increase in the maximum velocity, a 10-fold decrease of the Km, app. value for the donor and a 10-fold increase of the benzylpenicillin concentration required to inhibit the enzyme activity by 50% (ID50 value). Temperatures of -35 degrees C or below are required to completely inhibit the membrane-bound enzyme in the frozen state. Cetyltrimethylammonium bromide extracts the transpeptidase both from the isolated membranes and, with a much higher yield, from the intact mycelium. The extracted enzyme is not active in the frozen state, requires detergent for activity, has decreased Km, app. values for both donor and acceptor, exhibits the same sensitivity to benzylpenicillin and cephalosporin C as the membrane-bound transpeptidase (in liquid suspensions) and, like this latter enzyme, has no DD-carboxypeptidase activity. The detergent-extracted transpeptidase penetrates gels of Sephadex-100 and is not sedimented at 200 000 X g.", "contents": "The catalytic activity and penicillin sensitivity in the liquid and frozen states of membrane-bound and detergent-solubilised transpeptidase of Streptomyces R61. The Km, app. values of the membrane-bound transpeptidase of Streptomyces R61 for the donor Ac2-L-Lys-D-Ala-D-Ala and the acceptor Gly-Gly are not affected by temperature variations when the reaction mixtures are incubated in liquid suspensions. At -5 degrees C, the incubation can be carried out either in the liquid or in the frozen state. The enzyme is active in the latter state. In the frozen state, the Km, app. value for the acceptor remains unchanged but there is a 3-fold increase in the maximum velocity, a 10-fold decrease of the Km, app. value for the donor and a 10-fold increase of the benzylpenicillin concentration required to inhibit the enzyme activity by 50% (ID50 value). Temperatures of -35 degrees C or below are required to completely inhibit the membrane-bound enzyme in the frozen state. Cetyltrimethylammonium bromide extracts the transpeptidase both from the isolated membranes and, with a much higher yield, from the intact mycelium. The extracted enzyme is not active in the frozen state, requires detergent for activity, has decreased Km, app. values for both donor and acceptor, exhibits the same sensitivity to benzylpenicillin and cephalosporin C as the membrane-bound transpeptidase (in liquid suspensions) and, like this latter enzyme, has no DD-carboxypeptidase activity. The detergent-extracted transpeptidase penetrates gels of Sephadex-100 and is not sedimented at 200 000 X g."}
{"id": "PMID:240709", "title": "Hydrogen-exchange study of the conformational stability of human carbonic-anhydrase B and its metallocomplexes.", "content": "In the range of pH 4.6--8.8, 25 degrees C, the apoenzyme of carbonic anhydrase B shows no evidence of any gross conformational changes, as studied by the hydrogen-deuterium exchange method. At pH 4.6 the addition of Co(II), Cd(II) or Mn(II) to the apoenzyme results in a destabilization of the native protein conformation, but in the range of pH 5.5--8.8 these metal ions, and Zn(II), slightly increase the conformational stability of the protein, in so far as they reduce the probability phi of solvent exposure of the peptide groups. In comparison with other proteins studied, native carbonic anhydrase is characterized by a rather compact conformation; for half of the peptide groups the probability of solvent exposure is less than 10(-4), corresponding to changes in standard free energy larger than 5.5 kcal mol-1 (23 kJ mol-1) following the conformational transitions by which these groups are exposed to the solvent.", "contents": "Hydrogen-exchange study of the conformational stability of human carbonic-anhydrase B and its metallocomplexes. In the range of pH 4.6--8.8, 25 degrees C, the apoenzyme of carbonic anhydrase B shows no evidence of any gross conformational changes, as studied by the hydrogen-deuterium exchange method. At pH 4.6 the addition of Co(II), Cd(II) or Mn(II) to the apoenzyme results in a destabilization of the native protein conformation, but in the range of pH 5.5--8.8 these metal ions, and Zn(II), slightly increase the conformational stability of the protein, in so far as they reduce the probability phi of solvent exposure of the peptide groups. In comparison with other proteins studied, native carbonic anhydrase is characterized by a rather compact conformation; for half of the peptide groups the probability of solvent exposure is less than 10(-4), corresponding to changes in standard free energy larger than 5.5 kcal mol-1 (23 kJ mol-1) following the conformational transitions by which these groups are exposed to the solvent."}
{"id": "PMID:240710", "title": "Occurrence and properties of a prostaglandin F2alpha receptor in bovine corpora lutea.", "content": "Prostaglandin F2alpha was specifically bound by a particulate fraction from bovine corpora lutea. The rate constants for the association (7.5 X 10(3) M-1 S-1) and dissociation (2.1 X 10-4 S-1) reactions gave a dissociation constant of 2.8 X 10(-8) M which is similar to that determined from a Scatchard plot of binding data at equilibrium (5 X 10(-8) M). The receptor was stable for several hours at 23 degrees C but was rapidly destroyed at 37 degrees C. The pH optimum for the binding reaction was 6.3. The receptor had high specificity for prostaglandin F2alpha and had much lower affinities for other prostaglandins. Luteinizing and follicle-stimulating hormones had no effect on the prostaglandin F2alpha-receptor interaction.", "contents": "Occurrence and properties of a prostaglandin F2alpha receptor in bovine corpora lutea. Prostaglandin F2alpha was specifically bound by a particulate fraction from bovine corpora lutea. The rate constants for the association (7.5 X 10(3) M-1 S-1) and dissociation (2.1 X 10-4 S-1) reactions gave a dissociation constant of 2.8 X 10(-8) M which is similar to that determined from a Scatchard plot of binding data at equilibrium (5 X 10(-8) M). The receptor was stable for several hours at 23 degrees C but was rapidly destroyed at 37 degrees C. The pH optimum for the binding reaction was 6.3. The receptor had high specificity for prostaglandin F2alpha and had much lower affinities for other prostaglandins. Luteinizing and follicle-stimulating hormones had no effect on the prostaglandin F2alpha-receptor interaction."}
{"id": "PMID:240711", "title": "Temperature-induced transitions in the conformation of intermediates in the hydrolytic cycle of myosin.", "content": "The conformations of the transitory intermediates of the myosin ATPase occurring during the hydrolytic cycle, enzyme without ligand, enzyme-substrate complex and two different forms of enzyme-product complex, have been characterized in terms of numbers and classes of reactive thiol groups based on incorporation of radioactively labeled alkylation reagent. The techniques employed allowed this to be done under steady-state conditions in the presence of high ligand concentrations on intact myosin from rabbit fast skeletal muscles at low ionic strength where the protein is in the gel state as it is in muscle. The binding of a divalent cation (Mg2+ or Ca2+) nucleotide complex exposes thiol-1 as well as thiol-2 groups. The long-lived ATPase intermediate occurring at temperatures above 10 degrees C adopts the same conformation with Mg2+ and Ca2+ ions. This intermediate does not protect the thiol-1 and thiol-2 groups but exposes a number of thiol-3 groups which seem to be located distant from the active site. The conformation of the intermediate prevailing in the presence of ATP changes with lowering temperature below 10 degrees C and is identical with that found in the presence of ADP at 0 degree C indicating a change in the rate-limiting step of the hydrolytic cycle. In the absence of divalent cations no such temperature-dependent change in conformation was observed. Evaluation of the activation entropies shows that the structure of the long-lived intermediate occurring above 10 degrees C in the presence of Mg2+ ions goes through a transformation from low to high order at around 20 degrees C. In the case of the monovalent-cation-stimulated ATPase a constant activation energy of around 70 kJ/mol, typical of many enzyme reactions, was found over the entire temperature range from 0--35 degrees C.", "contents": "Temperature-induced transitions in the conformation of intermediates in the hydrolytic cycle of myosin. The conformations of the transitory intermediates of the myosin ATPase occurring during the hydrolytic cycle, enzyme without ligand, enzyme-substrate complex and two different forms of enzyme-product complex, have been characterized in terms of numbers and classes of reactive thiol groups based on incorporation of radioactively labeled alkylation reagent. The techniques employed allowed this to be done under steady-state conditions in the presence of high ligand concentrations on intact myosin from rabbit fast skeletal muscles at low ionic strength where the protein is in the gel state as it is in muscle. The binding of a divalent cation (Mg2+ or Ca2+) nucleotide complex exposes thiol-1 as well as thiol-2 groups. The long-lived ATPase intermediate occurring at temperatures above 10 degrees C adopts the same conformation with Mg2+ and Ca2+ ions. This intermediate does not protect the thiol-1 and thiol-2 groups but exposes a number of thiol-3 groups which seem to be located distant from the active site. The conformation of the intermediate prevailing in the presence of ATP changes with lowering temperature below 10 degrees C and is identical with that found in the presence of ADP at 0 degree C indicating a change in the rate-limiting step of the hydrolytic cycle. In the absence of divalent cations no such temperature-dependent change in conformation was observed. Evaluation of the activation entropies shows that the structure of the long-lived intermediate occurring above 10 degrees C in the presence of Mg2+ ions goes through a transformation from low to high order at around 20 degrees C. In the case of the monovalent-cation-stimulated ATPase a constant activation energy of around 70 kJ/mol, typical of many enzyme reactions, was found over the entire temperature range from 0--35 degrees C."}
{"id": "PMID:240712", "title": "Specificity of the glutamine-binding site involved in the reguation of glutamine-synthetase activity in hepatoma tissue-culture cells.", "content": "Glutamine accelerates the degradation of glutamine synthetase in hepatoma tissue culture cells. Compounds structurally related to glutamine were tested for their ability to mimic or antagonize this effect of glutamine. 6-Diazo-5-oxo-L-norleucine, like glutamine depressed the activity of glutamine synthetase in hepatoma tissue culture cells. L-Methionine sulfone, albizzine, L-methionine sulfoxide, L-gamma-glutamyl hydrazide and gamma-N-methyl-L-glutamine (listed in order of decreasing potency) were antagonists which prevented the effect of glutamine on glutamine synthetase activity. These antagonists had little effect on glutamine transport or protein synthesis of hepatoma tissue culture cells and their effects were reversible. The effects of compounds on gluatmine synthetase activity in cell-free extracts of the cells were examined. Diazo-oxonorleucine and albizzine inhibited neither the transferase nor the synthetase activity of glutamine synthetase. This observation is interpreted to mean that the glutamine-binding site involved in the regulation of glutamine synthetase activity of hepatoma tissue culture cells is not the active site of the enzyme.", "contents": "Specificity of the glutamine-binding site involved in the reguation of glutamine-synthetase activity in hepatoma tissue-culture cells. Glutamine accelerates the degradation of glutamine synthetase in hepatoma tissue culture cells. Compounds structurally related to glutamine were tested for their ability to mimic or antagonize this effect of glutamine. 6-Diazo-5-oxo-L-norleucine, like glutamine depressed the activity of glutamine synthetase in hepatoma tissue culture cells. L-Methionine sulfone, albizzine, L-methionine sulfoxide, L-gamma-glutamyl hydrazide and gamma-N-methyl-L-glutamine (listed in order of decreasing potency) were antagonists which prevented the effect of glutamine on glutamine synthetase activity. These antagonists had little effect on glutamine transport or protein synthesis of hepatoma tissue culture cells and their effects were reversible. The effects of compounds on gluatmine synthetase activity in cell-free extracts of the cells were examined. Diazo-oxonorleucine and albizzine inhibited neither the transferase nor the synthetase activity of glutamine synthetase. This observation is interpreted to mean that the glutamine-binding site involved in the regulation of glutamine synthetase activity of hepatoma tissue culture cells is not the active site of the enzyme."}
{"id": "PMID:240713", "title": "Circular-dichroic spectra of vasopressin analogues and their cyclic fragments.", "content": "The circular dichroic spectra of [Arg8]vasopressin, [Mpr1, Arg8]vasopressin, [Mpr1, D-Arg8]-vasopressin, pressinamide, deaminopressinamide, tocinamide, deaminotocinamide, [Leu4, D-Arg8]-vasotocin, [Mpr1, Leu4, D-Arg8]vasotocin and [Phe2, Lys8]vasopressin have been studied. All these substances showed a characteristic positive dichroic band at about 225 nm due to the presence of tyrosine in sequence position 2. The intensity of this band was affected by interactions between the tyrosine side-chain and other structural elements in the molecule, such as the Na-amino group, the side-chain of phenylalanine in position 3 and the linear C-terminal peptide. Analysis of the response of this band to structural modifications of the molecule and change in the solvent (particularly comparing neutral aqueous solutions with hexafluoroacetone solutions) allowed some conformational conclusions. The linear C-terminal tripeptide is probably situated over the cyclic portion of the molecule both in vasopressin and oxytocin substances. Its steric interaction with the tyrosine side-chain seems to be particularly efficient in molecules containing D-arginine in position 8. In the vasopressin series the stacking interaction of neighbouring aromatic amino acid residues furthermore limits the conformational freedom of the tyrosine side-chain and also probably distorts the dihedral angles of residues 1-3 in comparison with oxytocin. The interactions of phenylalanine and arginine with tyrosine relatively decrease the conformational effects of the primary amino group. Consequently the local conformation of vasopressin in the region of the tyrosine residue is more rigid and less sensitive to changes in medium than that of oxytocin. The circular dichroic spectra did not show any basic conformational differences in the backbone peptide chain of oxytocin and vasopressin substances. A weak negative disulphide band at about 290 nm could be observed in the spectra of both series of substances.", "contents": "Circular-dichroic spectra of vasopressin analogues and their cyclic fragments. The circular dichroic spectra of [Arg8]vasopressin, [Mpr1, Arg8]vasopressin, [Mpr1, D-Arg8]-vasopressin, pressinamide, deaminopressinamide, tocinamide, deaminotocinamide, [Leu4, D-Arg8]-vasotocin, [Mpr1, Leu4, D-Arg8]vasotocin and [Phe2, Lys8]vasopressin have been studied. All these substances showed a characteristic positive dichroic band at about 225 nm due to the presence of tyrosine in sequence position 2. The intensity of this band was affected by interactions between the tyrosine side-chain and other structural elements in the molecule, such as the Na-amino group, the side-chain of phenylalanine in position 3 and the linear C-terminal peptide. Analysis of the response of this band to structural modifications of the molecule and change in the solvent (particularly comparing neutral aqueous solutions with hexafluoroacetone solutions) allowed some conformational conclusions. The linear C-terminal tripeptide is probably situated over the cyclic portion of the molecule both in vasopressin and oxytocin substances. Its steric interaction with the tyrosine side-chain seems to be particularly efficient in molecules containing D-arginine in position 8. In the vasopressin series the stacking interaction of neighbouring aromatic amino acid residues furthermore limits the conformational freedom of the tyrosine side-chain and also probably distorts the dihedral angles of residues 1-3 in comparison with oxytocin. The interactions of phenylalanine and arginine with tyrosine relatively decrease the conformational effects of the primary amino group. Consequently the local conformation of vasopressin in the region of the tyrosine residue is more rigid and less sensitive to changes in medium than that of oxytocin. The circular dichroic spectra did not show any basic conformational differences in the backbone peptide chain of oxytocin and vasopressin substances. A weak negative disulphide band at about 290 nm could be observed in the spectra of both series of substances."}
{"id": "PMID:240714", "title": "NAD(P)+ analogues: tools for the investigation of the active site of oestradiol 17beta-dehydrogenase from human placenta.", "content": "Oestradiol-17beta:NAD+ 17-oxidoreductase from human placenta can accept coenzyme analogues of NAD+ and NADP+ where the amide group is replaced by methyl ketone, nitrile or thioamide. The inhibition with analogues of NAD+ has been studied. The presence of a substituent at C-3 of the pyridinium ring is necessary for the binding. The inhibition by C-4 methylated analogues is very poor, and the effect of a methyl group at C-5 depends on the substituent at C-3. The 1,4,5,6-tetrahydronicotinamide adenine dinucleotide is a competitive inhibitor. Nicotinamide 8-bromoadenine dinucleotide and nicotinamide 8-thioadenine dinucleotide are efficient hydrogen acceptors.", "contents": "NAD(P)+ analogues: tools for the investigation of the active site of oestradiol 17beta-dehydrogenase from human placenta. Oestradiol-17beta:NAD+ 17-oxidoreductase from human placenta can accept coenzyme analogues of NAD+ and NADP+ where the amide group is replaced by methyl ketone, nitrile or thioamide. The inhibition with analogues of NAD+ has been studied. The presence of a substituent at C-3 of the pyridinium ring is necessary for the binding. The inhibition by C-4 methylated analogues is very poor, and the effect of a methyl group at C-5 depends on the substituent at C-3. The 1,4,5,6-tetrahydronicotinamide adenine dinucleotide is a competitive inhibitor. Nicotinamide 8-bromoadenine dinucleotide and nicotinamide 8-thioadenine dinucleotide are efficient hydrogen acceptors."}
{"id": "PMID:240715", "title": "Intracellular distribution of neutral proteinases and inhibitors in pig leucocytes. Isolation of two inhibitors of neutral proteinases.", "content": "Granule and post-granular-supernatant fractions were obtained from pig leucocyte cells by differential centrifugation in 0.34 M sucrose. Granule extract possesses proteinase activity at acid and at neutral pH. Three groups of neutral and a group of acid proteinases were isolated from granule extracts by chromatography on DEAE-cellulose. In the first group are present elastase-like and plasminogen-activator proteinases, that are inhibited by diisopropylphosphorofluoridate, alpha1-antitrypsin, intracellular leucocyte inhibitor and partly with p-aminomethylbenzoic acid and Trasylol. The second group of neutral proteinases is unstable under the conditions of isolation used the third group of neutral proteinases comprises collagenases that are inhibited by ethylenediamine tetraacetic acid disodium salt, alpha1-antitrypsin and leucocyte inhibitor. The acid proteinases are inhibited only with pepstatin, up to 90%. In the post-granular supernatant was found the acid proteinase activity towards hemoglobin and casein, and non-stable neutral proteolytic activity towards bovine serum albumin and serum gamma globulin. In the post-granular supernatant also the inhibitors of neutral proteinases were found. By gel filtration on Sephadex G-100 and ion-exchange chromatography on CM-cellulose two inhibitors of neutral proteinases were isolated. The majority of the inhibitor capacity (about 80%) of post-granular supernatant was eluted together with ovalbumin (Mr 43000) and the remainder with cytochrome c (12300). These inhibitors inhibit the granule neutral proteinases, acting on all substrates used, but do not inhibit granule acid proteinase. Inhibition effects of post-granular-supernatant inhibitors on trypsin and chymotrypsin were obtained only when bovine serum albumin was used as substrate. Inhibitors of post-granular supernatant are stable at pH 6-8, but unstable in the pH rnage 2-5 and are thermolabile.", "contents": "Intracellular distribution of neutral proteinases and inhibitors in pig leucocytes. Isolation of two inhibitors of neutral proteinases. Granule and post-granular-supernatant fractions were obtained from pig leucocyte cells by differential centrifugation in 0.34 M sucrose. Granule extract possesses proteinase activity at acid and at neutral pH. Three groups of neutral and a group of acid proteinases were isolated from granule extracts by chromatography on DEAE-cellulose. In the first group are present elastase-like and plasminogen-activator proteinases, that are inhibited by diisopropylphosphorofluoridate, alpha1-antitrypsin, intracellular leucocyte inhibitor and partly with p-aminomethylbenzoic acid and Trasylol. The second group of neutral proteinases is unstable under the conditions of isolation used the third group of neutral proteinases comprises collagenases that are inhibited by ethylenediamine tetraacetic acid disodium salt, alpha1-antitrypsin and leucocyte inhibitor. The acid proteinases are inhibited only with pepstatin, up to 90%. In the post-granular supernatant was found the acid proteinase activity towards hemoglobin and casein, and non-stable neutral proteolytic activity towards bovine serum albumin and serum gamma globulin. In the post-granular supernatant also the inhibitors of neutral proteinases were found. By gel filtration on Sephadex G-100 and ion-exchange chromatography on CM-cellulose two inhibitors of neutral proteinases were isolated. The majority of the inhibitor capacity (about 80%) of post-granular supernatant was eluted together with ovalbumin (Mr 43000) and the remainder with cytochrome c (12300). These inhibitors inhibit the granule neutral proteinases, acting on all substrates used, but do not inhibit granule acid proteinase. Inhibition effects of post-granular-supernatant inhibitors on trypsin and chymotrypsin were obtained only when bovine serum albumin was used as substrate. Inhibitors of post-granular supernatant are stable at pH 6-8, but unstable in the pH rnage 2-5 and are thermolabile."}
{"id": "PMID:240716", "title": "Quantitative determination of the conformation of ATP in aqueous solution using the lanthanide cations as nuclear-magnetic-resonance probes.", "content": "Chemical shift perturbations of the eight 1H resonances and of the three 31P resonances in the nuclear magnetic resonance spectra of ATP in 2H2O, pH 6.0, have been induced by specifically bound lanthanide cations Ln3+ (Ln = Pr, Nd, Eu, Yb). After separation of contact (through bond) perturbations the resultant through-space shifts, which are found to have axial symmetry, are used in an analysis of the conformation of the Ln3+ -ATP complex. A computer program was used to search for the conformations of the molecule which fit the nuclear magnetic resonance data. The \"best\" solutions obtained represent a small closely interrelated family of conformations. Effects of the cation Gd3+ on the longitudinal relaxation rates of five of the protons of ATP were also measured and used to confirm the conformational family. One of these conformations corresponds closely to one of the crystal structure forms, with an anti arrangement of the base-ribose unit and and a right-hand helical phosphate chain folded towards the adenine part of the molecule. The lanthanide ion binds predominantly to the beta and gamma phosphates and does not interact with the purine ring, these two centres being separated by at least one water molecule.", "contents": "Quantitative determination of the conformation of ATP in aqueous solution using the lanthanide cations as nuclear-magnetic-resonance probes. Chemical shift perturbations of the eight 1H resonances and of the three 31P resonances in the nuclear magnetic resonance spectra of ATP in 2H2O, pH 6.0, have been induced by specifically bound lanthanide cations Ln3+ (Ln = Pr, Nd, Eu, Yb). After separation of contact (through bond) perturbations the resultant through-space shifts, which are found to have axial symmetry, are used in an analysis of the conformation of the Ln3+ -ATP complex. A computer program was used to search for the conformations of the molecule which fit the nuclear magnetic resonance data. The \"best\" solutions obtained represent a small closely interrelated family of conformations. Effects of the cation Gd3+ on the longitudinal relaxation rates of five of the protons of ATP were also measured and used to confirm the conformational family. One of these conformations corresponds closely to one of the crystal structure forms, with an anti arrangement of the base-ribose unit and and a right-hand helical phosphate chain folded towards the adenine part of the molecule. The lanthanide ion binds predominantly to the beta and gamma phosphates and does not interact with the purine ring, these two centres being separated by at least one water molecule."}
{"id": "PMID:240717", "title": "Acetyl-coenzyme-A carboxylase from rat liver. Subunit structure and proteolytic modification.", "content": "The subunit structure of rat liver acetyl-coenzyme-A carboxylase has been studied by polyacrylamide gel electrophoresis in the presence of dodecylsulfate. A number of individual preparations of the enzyme purified by the same procedures exhibited three different types of electrophoretic patterns as follows: first, a single slow-moving protein bands (Mr 230000); secondly, two adjacent fast-moving protein band (M4 124000 and 118 000); finally, all three protein bands. With the use of the [14C]biotin-labelled enzyme, the biotinyl prosthetic group was shown to be associated with the polypeptide of 230000 Mr as well as with that of 124000 Mr, but not with the polypeptide of 118000 Mr. Studies were next made with the labelled enzyme to examine the possibility that the two light polypeptides might have been formed by proteolytic modification of the heavy polypeptide during the procedures used for the purification of the enzyme. Treatment of the enzyme with trypsin or chymotrypsin resulted in cleavage of the heavy polypeptide into two nonidentical polypeptides with molecular weights of approximately 120000. Incubation of the enzyme with proteases derived from rat liver converted the heavy polypeptide into lighter polypeptides of 80000-130000 Mr. Acetyl-CoA carboxylase isolated from crude rat liver extracts by means of immunoprecipitation with specific antibody invariably showed only the heavy polypeptide. The biotin content of the enzyme was found to be 1 mol per 237000 g protein. These results indicate that rat liver acetyl-CoA carboxylase, unlike bacterial and plant biotin enzymes, has only one kind of subunit, which has a molecular weight of 230000 and contains one molecular of biotin. Thus, the mammalian enzyme exhibits a highly integrated subunit structure.", "contents": "Acetyl-coenzyme-A carboxylase from rat liver. Subunit structure and proteolytic modification. The subunit structure of rat liver acetyl-coenzyme-A carboxylase has been studied by polyacrylamide gel electrophoresis in the presence of dodecylsulfate. A number of individual preparations of the enzyme purified by the same procedures exhibited three different types of electrophoretic patterns as follows: first, a single slow-moving protein bands (Mr 230000); secondly, two adjacent fast-moving protein band (M4 124000 and 118 000); finally, all three protein bands. With the use of the [14C]biotin-labelled enzyme, the biotinyl prosthetic group was shown to be associated with the polypeptide of 230000 Mr as well as with that of 124000 Mr, but not with the polypeptide of 118000 Mr. Studies were next made with the labelled enzyme to examine the possibility that the two light polypeptides might have been formed by proteolytic modification of the heavy polypeptide during the procedures used for the purification of the enzyme. Treatment of the enzyme with trypsin or chymotrypsin resulted in cleavage of the heavy polypeptide into two nonidentical polypeptides with molecular weights of approximately 120000. Incubation of the enzyme with proteases derived from rat liver converted the heavy polypeptide into lighter polypeptides of 80000-130000 Mr. Acetyl-CoA carboxylase isolated from crude rat liver extracts by means of immunoprecipitation with specific antibody invariably showed only the heavy polypeptide. The biotin content of the enzyme was found to be 1 mol per 237000 g protein. These results indicate that rat liver acetyl-CoA carboxylase, unlike bacterial and plant biotin enzymes, has only one kind of subunit, which has a molecular weight of 230000 and contains one molecular of biotin. Thus, the mammalian enzyme exhibits a highly integrated subunit structure."}
{"id": "PMID:240718", "title": "Hepatic nucleases. 1. Methods for the specific determination and characterization in rat liver.", "content": "With a view to the study of the subcellular localization of nucleases, methods ensuring the homogenates. The ribonuclease activity of rat liver is due to the three enzymes with different pH optimun. For acid ribonuclease (pH optimun 5.3), it is possible to avoid interference from the other ribonucleases by performing the incubation at pH 5. Neutral ribonuclease (pH optimum 7.6) is differentiated by relying on its sensitivity to the natural inhibitor from the supernatant of liver homogenate. Comparison of activities before and after pretreatment at 50 degrees C in acid medium permits the specific measurement of alkaline ribonuclease (pH optimum 8.8). The optimal conditions for the determination in liver homogenates of two deoxyribonucleases and of an enzyme acting on polyriboadenylate are also described. The activity of these various nucleases is compared and some of their properties are investigated.", "contents": "Hepatic nucleases. 1. Methods for the specific determination and characterization in rat liver. With a view to the study of the subcellular localization of nucleases, methods ensuring the homogenates. The ribonuclease activity of rat liver is due to the three enzymes with different pH optimun. For acid ribonuclease (pH optimun 5.3), it is possible to avoid interference from the other ribonucleases by performing the incubation at pH 5. Neutral ribonuclease (pH optimum 7.6) is differentiated by relying on its sensitivity to the natural inhibitor from the supernatant of liver homogenate. Comparison of activities before and after pretreatment at 50 degrees C in acid medium permits the specific measurement of alkaline ribonuclease (pH optimum 8.8). The optimal conditions for the determination in liver homogenates of two deoxyribonucleases and of an enzyme acting on polyriboadenylate are also described. The activity of these various nucleases is compared and some of their properties are investigated."}
{"id": "PMID:240719", "title": "Hepatic nuclease. 2. Association of polyadenylase, alkaline ribonuclease and deoxyribonuclease with rat-liver mitochondria.", "content": "Six types of nuclease activities were found to be concentrated in the large granule fraction isolated from rat liver homogenastes by differential centrifugation. Analysis by density equilibration shows that three nucleases are associated with mitochondria: an alkaline ribonulcease (pH optimum 8.8), an alkaline deoxyribonuclease (pH optimum 7.6) and an enzyme acting on polyriboadenylate (pH optimum 7.5). When the outer mitochondrial membrane is ruptured in hypotonic medium, the three mitochondrial nucleases are partially solubilized. Solubilization is however obtained by addition of KCL to the suspension medium. It is concluded that mitochondrial nucleases are localized in the intermembrane space but that an adsorption to the outer face of the inner mitochondrial membrane occurs in sucrose 0.25 M. The mitochondrial localization of alkaline ribonuclease, alkaline deoxyribonuclease and polyadenylate accounts for at least 80% of the activity of liver homogenate; nevertheless, an excess of these enzymes is present in the microsomal fraction. Although no definite conculusion can be reached for the significance of this observation, it is shown by density equilibration analysis that these nuclease are not associated either with ribosomes or with the membranes which are the major component of the microsomal fraction.", "contents": "Hepatic nuclease. 2. Association of polyadenylase, alkaline ribonuclease and deoxyribonuclease with rat-liver mitochondria. Six types of nuclease activities were found to be concentrated in the large granule fraction isolated from rat liver homogenastes by differential centrifugation. Analysis by density equilibration shows that three nucleases are associated with mitochondria: an alkaline ribonulcease (pH optimum 8.8), an alkaline deoxyribonuclease (pH optimum 7.6) and an enzyme acting on polyriboadenylate (pH optimum 7.5). When the outer mitochondrial membrane is ruptured in hypotonic medium, the three mitochondrial nucleases are partially solubilized. Solubilization is however obtained by addition of KCL to the suspension medium. It is concluded that mitochondrial nucleases are localized in the intermembrane space but that an adsorption to the outer face of the inner mitochondrial membrane occurs in sucrose 0.25 M. The mitochondrial localization of alkaline ribonuclease, alkaline deoxyribonuclease and polyadenylate accounts for at least 80% of the activity of liver homogenate; nevertheless, an excess of these enzymes is present in the microsomal fraction. Although no definite conculusion can be reached for the significance of this observation, it is shown by density equilibration analysis that these nuclease are not associated either with ribosomes or with the membranes which are the major component of the microsomal fraction."}
{"id": "PMID:240720", "title": "A 4-methoxybenzoate O-demethylase from Pseudomonas putida. A new type of monooxygenase system.", "content": "A strain of Pseudomonas putida grown on 4-methoxybenzoate as sole carbon source contains an enzyme system for the O-demethylation of this substrate. The enzyme system is purifiable and can be separated into two components: an NADH-dependent reductase and an iron-containing and acid-labile-sulfur-containing monooxygenase. The reductase, of molecular weight 42000 and containing two chromophores, an FMN and an iron-sulfur complex (EPR at g = 1.95), reduces both one-electron and two-electron acceptors (i.e., ferricyanide, 2,6-dichloroindophenol, cytochrome c, and cytochrome b5) at an optimum pH of 8.0. Increasing ionic strength affects these activities differently. The absolute spectrum of the oxidized displays distinct absorption peaks at 409 and 463 nm and a small shoulder between 538 and 554 nm. Treatment with dithionite or NADH reduces the absorbance throughout the visible range, yielding a spectrum with small maxima at 402 and 538 nm. Spectroscopic characteristics of the reductase indicate a tight coupling between its two chromophores. The iron-containing and acid-labile-sulfur-containing monooxygenase, which has a molecular weight of about 120000, contains an iron-sulfur chromophore with an EPR signal at g = 1.90. This protein is a dimer whose subunits each have a molecular weight of about 50000 and are perhaps identical. The optical absorption properties are somewhat unusual. In contrast to other iron-sulfur proteins, there is no significant peak near 415 nm in the absorption spectrum of the oxidized protein, but rather one at 455 nm. The presence of the substrate 4-methoxybenzoate increases both the NADH-dependent reductase. Hydroxylation can be achieved by the monooxygenase also in absence of the reductase with artifical reductants. This enzyme opens a new group of oxygenases within the classification scheme, i.e., iron-containing and labile-sulfur-containing monooxygenases. From the reported data, a scheme for the interaction of the isolated pigments and their relationship to various acceptors is proposed.", "contents": "A 4-methoxybenzoate O-demethylase from Pseudomonas putida. A new type of monooxygenase system. A strain of Pseudomonas putida grown on 4-methoxybenzoate as sole carbon source contains an enzyme system for the O-demethylation of this substrate. The enzyme system is purifiable and can be separated into two components: an NADH-dependent reductase and an iron-containing and acid-labile-sulfur-containing monooxygenase. The reductase, of molecular weight 42000 and containing two chromophores, an FMN and an iron-sulfur complex (EPR at g = 1.95), reduces both one-electron and two-electron acceptors (i.e., ferricyanide, 2,6-dichloroindophenol, cytochrome c, and cytochrome b5) at an optimum pH of 8.0. Increasing ionic strength affects these activities differently. The absolute spectrum of the oxidized displays distinct absorption peaks at 409 and 463 nm and a small shoulder between 538 and 554 nm. Treatment with dithionite or NADH reduces the absorbance throughout the visible range, yielding a spectrum with small maxima at 402 and 538 nm. Spectroscopic characteristics of the reductase indicate a tight coupling between its two chromophores. The iron-containing and acid-labile-sulfur-containing monooxygenase, which has a molecular weight of about 120000, contains an iron-sulfur chromophore with an EPR signal at g = 1.90. This protein is a dimer whose subunits each have a molecular weight of about 50000 and are perhaps identical. The optical absorption properties are somewhat unusual. In contrast to other iron-sulfur proteins, there is no significant peak near 415 nm in the absorption spectrum of the oxidized protein, but rather one at 455 nm. The presence of the substrate 4-methoxybenzoate increases both the NADH-dependent reductase. Hydroxylation can be achieved by the monooxygenase also in absence of the reductase with artifical reductants. This enzyme opens a new group of oxygenases within the classification scheme, i.e., iron-containing and labile-sulfur-containing monooxygenases. From the reported data, a scheme for the interaction of the isolated pigments and their relationship to various acceptors is proposed."}
{"id": "PMID:240721", "title": "Intramolecular addition of the riboflavin side chain. Anion-catalyzed neutral photochemistry.", "content": "The presence of higher (greater than 0.2 M) concentrations of divalent anions A2- (hydrogenphosphate, sulfate) is found to accelerate as well as to change entirely the course of riboflavin photolysis: instead of 10-dealkylation to yield lumichrome, intramolecular addition of the 2'-hydroxyl group is found to occur at the peri-position C(9). The reaction is analogous to the \"photohydration\" of the flavin nucleus in the cationic state as described by Sch\u00f6llnhammer and Hemmerich [Eur. J. Biochem. (1974) 44, 561-577]. The final product of the new addition reaction arises from autoxidation of a dihydroflavin intermediate and exhibits the structure. It is thus representative for a new class of flavins (\"cyclo-dehydroflavins\"). Earlier reports on \"anomalous\" flavin photodegradation products absorbing around 410 nm [Holmstr\u00f6m (1964) Ark. Kem. 22, 281; Massey and Atherton (1962) J. Biol. Chem 237, 2965] are readily explained. The reaction is found to depend strictly on the presence of a nucleophilic function in the N(10)-side chain, e.g. N(10)-CH2-C(OH)RR' or even N(10)-(CH2)2-SO3-. Quenching experiments suggest that the new reaction occurs via the singlet state 1FLox while the normal photolysis is mediated by the triplet 3Flox. The new photoaddition is though to occur via a Flavin-A2- complex which creates sterically favorable conditions for C(9)/O(2'alpha)-interaction.", "contents": "Intramolecular addition of the riboflavin side chain. Anion-catalyzed neutral photochemistry. The presence of higher (greater than 0.2 M) concentrations of divalent anions A2- (hydrogenphosphate, sulfate) is found to accelerate as well as to change entirely the course of riboflavin photolysis: instead of 10-dealkylation to yield lumichrome, intramolecular addition of the 2'-hydroxyl group is found to occur at the peri-position C(9). The reaction is analogous to the \"photohydration\" of the flavin nucleus in the cationic state as described by Sch\u00f6llnhammer and Hemmerich [Eur. J. Biochem. (1974) 44, 561-577]. The final product of the new addition reaction arises from autoxidation of a dihydroflavin intermediate and exhibits the structure. It is thus representative for a new class of flavins (\"cyclo-dehydroflavins\"). Earlier reports on \"anomalous\" flavin photodegradation products absorbing around 410 nm [Holmstr\u00f6m (1964) Ark. Kem. 22, 281; Massey and Atherton (1962) J. Biol. Chem 237, 2965] are readily explained. The reaction is found to depend strictly on the presence of a nucleophilic function in the N(10)-side chain, e.g. N(10)-CH2-C(OH)RR' or even N(10)-(CH2)2-SO3-. Quenching experiments suggest that the new reaction occurs via the singlet state 1FLox while the normal photolysis is mediated by the triplet 3Flox. The new photoaddition is though to occur via a Flavin-A2- complex which creates sterically favorable conditions for C(9)/O(2'alpha)-interaction."}
{"id": "PMID:240722", "title": "Binding studies of NADPH to NADP-specific L-glutamate dehydrogenase from Saccharomyces cerevisiae.", "content": "Optical characteristics of enzyme-reduced coenzyme complexes of yeast NADP-specific glutamate dehydrogenase have been investigated in the presence and absence of product (L-glutamate) and in the presence or absence of phosphate. The phosphate effect, pointed out in a previous work, is found again: inorganic phosphate (Pi) destabilizes the binary complex (E - NADPH), the dissociation constant of which is equal to 14 muM, a value much higher than that determined in Tris-HCl buffer: Kd = 0.9 muM. Concerning the role of phosphate some assumptions are drawn up with respect to a similar behaviour of Pi toward yeast glutamate dehydrogenase and ADP toward the beef liver enzyme. In the same way, L-glutamate induces a stabilization of the binary complex; this latter effect is unchanged in the presence of phosphate, yet it is less marked than in the case of beef liver glutamate dehydrogenase. Protein fluorescence, nucleotide fluorescence and circular dichroism measurements allowed the determination of three identical and independent NADPH binding sites per hexameric active unit. In analogy with beef liver enzyme, it seems that yeast glutamate dehydrogenase is a good model to study anticooperativity in ligand binding.", "contents": "Binding studies of NADPH to NADP-specific L-glutamate dehydrogenase from Saccharomyces cerevisiae. Optical characteristics of enzyme-reduced coenzyme complexes of yeast NADP-specific glutamate dehydrogenase have been investigated in the presence and absence of product (L-glutamate) and in the presence or absence of phosphate. The phosphate effect, pointed out in a previous work, is found again: inorganic phosphate (Pi) destabilizes the binary complex (E - NADPH), the dissociation constant of which is equal to 14 muM, a value much higher than that determined in Tris-HCl buffer: Kd = 0.9 muM. Concerning the role of phosphate some assumptions are drawn up with respect to a similar behaviour of Pi toward yeast glutamate dehydrogenase and ADP toward the beef liver enzyme. In the same way, L-glutamate induces a stabilization of the binary complex; this latter effect is unchanged in the presence of phosphate, yet it is less marked than in the case of beef liver glutamate dehydrogenase. Protein fluorescence, nucleotide fluorescence and circular dichroism measurements allowed the determination of three identical and independent NADPH binding sites per hexameric active unit. In analogy with beef liver enzyme, it seems that yeast glutamate dehydrogenase is a good model to study anticooperativity in ligand binding."}
{"id": "PMID:240723", "title": "Cellulases from Sporocytophaga myxococcoides. Purification and Properties.", "content": "Two extracellular cellulases active on carboxymethylcellulose have been isolated from the culture supernatant of Sporocytophaga myxococcoides by a series of gel-filtration and ion-exchange chromatography steps. Cellulase II, being present in highest amount, had a molecular weight determined by gel electrophoresis of 52000, pI 4.75 and a relatively broad pH optimum (5.5--7.5). Cellulase I had a molecular weight of 46000. pI was 7.5 and the pH optimum 6.5--7.5. Both cellulases had a very low carbohydrate content, possibly present as impurities. They had fairly similar amino acid compositions. The specific acitivity of cellulase I was about 6 times higher than that of cellulase II. Both cellulases acted as endoglucanases. A cell-associated cellulase, present in amounts corresponding to about 10% of total activity, was partly purified. It showed similarities with cellulase II.", "contents": "Cellulases from Sporocytophaga myxococcoides. Purification and Properties. Two extracellular cellulases active on carboxymethylcellulose have been isolated from the culture supernatant of Sporocytophaga myxococcoides by a series of gel-filtration and ion-exchange chromatography steps. Cellulase II, being present in highest amount, had a molecular weight determined by gel electrophoresis of 52000, pI 4.75 and a relatively broad pH optimum (5.5--7.5). Cellulase I had a molecular weight of 46000. pI was 7.5 and the pH optimum 6.5--7.5. Both cellulases had a very low carbohydrate content, possibly present as impurities. They had fairly similar amino acid compositions. The specific acitivity of cellulase I was about 6 times higher than that of cellulase II. Both cellulases acted as endoglucanases. A cell-associated cellulase, present in amounts corresponding to about 10% of total activity, was partly purified. It showed similarities with cellulase II."}
{"id": "PMID:240724", "title": "The kinetics of the exchange of G-actin-bound 1: N6-ethenoadenosine 5'-triphosphate with ATP as followed by fluorescence.", "content": "1: N6-Ethenoadenosine 5'-triphosphate (epsilonATP), a fluorescent analog of ATP, binds to monomeric actin with a binding constant which is only about 5 times smaller than that of ATP. The spectroscopic changes which occur when epsilonATP binds to actin are studied and used to monitor the kinetics of nucleotide exchange. The first-order rate constant which is measured at a large excess of ATP over epsilonATP strongly depends on the ATP and Ca+ concentrations. This finding is explained by a mechanism in which the nucleotide dissociates much more easily from Ca2+-free than from Ca2+-bound actin. Of special interest is the temperature dependence of the dissociation rate constant. The Arrhenius plot shows a sharp bend near 24 degrees C.", "contents": "The kinetics of the exchange of G-actin-bound 1: N6-ethenoadenosine 5'-triphosphate with ATP as followed by fluorescence. 1: N6-Ethenoadenosine 5'-triphosphate (epsilonATP), a fluorescent analog of ATP, binds to monomeric actin with a binding constant which is only about 5 times smaller than that of ATP. The spectroscopic changes which occur when epsilonATP binds to actin are studied and used to monitor the kinetics of nucleotide exchange. The first-order rate constant which is measured at a large excess of ATP over epsilonATP strongly depends on the ATP and Ca+ concentrations. This finding is explained by a mechanism in which the nucleotide dissociates much more easily from Ca2+-free than from Ca2+-bound actin. Of special interest is the temperature dependence of the dissociation rate constant. The Arrhenius plot shows a sharp bend near 24 degrees C."}
{"id": "PMID:240725", "title": "Beta-Glucosidases from Cicer arietinum L. Purification and Properties of isoflavone-7-O-glucoside-specific beta-glucosidases.", "content": "Beta-Glucosidases specific for isoflavone 7-O-glucosides have been isolated from garbanzo plants, Cicer arietinum L. These aryl-beta-glucohydrolases occur in the different organs of the plant as multiple molecular forms. The major isoenzymes of the roots, the leaves and the hypocotyl were purified to electrophoretic homogeneity. When subjected to isoelectric focussing in polyac rylamide gels the electrophoretically homogeneous glucohydrolases were found to consist of one or two major and several minor enzymically active molecular species. In roots the beta-glucohydrolase isoenzymes constitute a considerable portion of the extractable protein, so that purification to an electrophoretically homogeneous form is easily attainable. All beta-glucosidases analyzed possess molecular weights in the range of 125 000 (ultracentrifugation) to 135 000 (Sephadex G-200) and contain two subunits of molecular weight near 68 000. The pH optimum for enzymic activity is 7--7.5 with a second optimum of 4.5--5. The isoelectric points of the various species range between pH 5.9 AND 7.1. Staining for glycoprotein was positive. Kinetic analysis demonstrated a pronounced specificity of the enzymes for aromatic substrates with glucose as the sugar moiety. alpha-Glucosides as well as disaccharides were not hydrolyzed at all. Isoflavone 7-O-glucosides are the most favoured substrates with a Km of 2 x 10(-5) M, while the Km with aromatic glucosides (i.e. salicin, 4-nitrophenyl glucoside) are 100 times larger. In addition the beta-glucosidases show a pronounced specificity for glucose in the 7-position of the flavonoid nucleus. Using isoflavone aglycones as substrates glucose transferase activity was also demonstrable. The beta-glucohydrolase activity is strongly inhibited by Hg2plus. This inhibition is partially reversible and preferentially influences the Km values of the enzymes compared to V. Agplus, glucono-1,5-lactone, ethyleneglycol monomethyl ether and glycerol are only weakly inhibitory, while glucose, p-chloromercuribenzoate and Cu2plus are without effect.", "contents": "Beta-Glucosidases from Cicer arietinum L. Purification and Properties of isoflavone-7-O-glucoside-specific beta-glucosidases. Beta-Glucosidases specific for isoflavone 7-O-glucosides have been isolated from garbanzo plants, Cicer arietinum L. These aryl-beta-glucohydrolases occur in the different organs of the plant as multiple molecular forms. The major isoenzymes of the roots, the leaves and the hypocotyl were purified to electrophoretic homogeneity. When subjected to isoelectric focussing in polyac rylamide gels the electrophoretically homogeneous glucohydrolases were found to consist of one or two major and several minor enzymically active molecular species. In roots the beta-glucohydrolase isoenzymes constitute a considerable portion of the extractable protein, so that purification to an electrophoretically homogeneous form is easily attainable. All beta-glucosidases analyzed possess molecular weights in the range of 125 000 (ultracentrifugation) to 135 000 (Sephadex G-200) and contain two subunits of molecular weight near 68 000. The pH optimum for enzymic activity is 7--7.5 with a second optimum of 4.5--5. The isoelectric points of the various species range between pH 5.9 AND 7.1. Staining for glycoprotein was positive. Kinetic analysis demonstrated a pronounced specificity of the enzymes for aromatic substrates with glucose as the sugar moiety. alpha-Glucosides as well as disaccharides were not hydrolyzed at all. Isoflavone 7-O-glucosides are the most favoured substrates with a Km of 2 x 10(-5) M, while the Km with aromatic glucosides (i.e. salicin, 4-nitrophenyl glucoside) are 100 times larger. In addition the beta-glucosidases show a pronounced specificity for glucose in the 7-position of the flavonoid nucleus. Using isoflavone aglycones as substrates glucose transferase activity was also demonstrable. The beta-glucohydrolase activity is strongly inhibited by Hg2plus. This inhibition is partially reversible and preferentially influences the Km values of the enzymes compared to V. Agplus, glucono-1,5-lactone, ethyleneglycol monomethyl ether and glycerol are only weakly inhibitory, while glucose, p-chloromercuribenzoate and Cu2plus are without effect."}
{"id": "PMID:240726", "title": "The mechanism of the halothane-dependent efflux of calcium from rat-liver mitochondria.", "content": "The halothane-dependent, calcium-induced loss of respiratory control in rat liver mitochondria [1, 2] is Mg2plus -dependent and is accompanied by an enhanced mitochondrial swelling. It is suggested that this swelling reflects an increase in calcium activity in the matrix space, due to a decrease in binding of the accumulated cation. This change in the partition of intramitochondrial calcium is correlated with an inhibition by halothane of energy-independent, calcium-induced swelling. The enhanced swelling associated with the active accumulation of calcium in the presence of halothane does not lead to a marked increase in permeability to other ions. Nevertheless, under conditions of energised calcium uptake, and in the presence of Mg2plus, a halothane-dependent, ruthenium red-insensitive efflux of calcium is observed. This is consistent with the proposed halothane-dependent increase in the matrix activity of accumulated Ca2plus. It is suggested that this mechanism accounts for the previously postulated [2] futile cycle of calcium uptake and release induced by halothane in rat liver mitochondria.", "contents": "The mechanism of the halothane-dependent efflux of calcium from rat-liver mitochondria. The halothane-dependent, calcium-induced loss of respiratory control in rat liver mitochondria [1, 2] is Mg2plus -dependent and is accompanied by an enhanced mitochondrial swelling. It is suggested that this swelling reflects an increase in calcium activity in the matrix space, due to a decrease in binding of the accumulated cation. This change in the partition of intramitochondrial calcium is correlated with an inhibition by halothane of energy-independent, calcium-induced swelling. The enhanced swelling associated with the active accumulation of calcium in the presence of halothane does not lead to a marked increase in permeability to other ions. Nevertheless, under conditions of energised calcium uptake, and in the presence of Mg2plus, a halothane-dependent, ruthenium red-insensitive efflux of calcium is observed. This is consistent with the proposed halothane-dependent increase in the matrix activity of accumulated Ca2plus. It is suggested that this mechanism accounts for the previously postulated [2] futile cycle of calcium uptake and release induced by halothane in rat liver mitochondria."}
{"id": "PMID:240727", "title": "Bulbocapnine's ability to antagonize the adrenergic inhibitory action of dopamine and analogs.", "content": "Dopamine in the presence of cocaine, 5,6-dihydroxy-2-dimethylaminotetralin (M-7), apomorphine and N,N-dimethyldopamine produced dose dependent inhibition on the heart rate increase due to stimulation of the right cardioaccelerator postganglionic nerves. Inhibitory actions of these compounds were antagonized by bulbocapnine. Also bulbocapnine antagonized the blood pressure increase due to N,N-dimethyldopamine but did not antagonize the pressor response of dopamine.", "contents": "Bulbocapnine's ability to antagonize the adrenergic inhibitory action of dopamine and analogs. Dopamine in the presence of cocaine, 5,6-dihydroxy-2-dimethylaminotetralin (M-7), apomorphine and N,N-dimethyldopamine produced dose dependent inhibition on the heart rate increase due to stimulation of the right cardioaccelerator postganglionic nerves. Inhibitory actions of these compounds were antagonized by bulbocapnine. Also bulbocapnine antagonized the blood pressure increase due to N,N-dimethyldopamine but did not antagonize the pressor response of dopamine."}
{"id": "PMID:240728", "title": "Effects of clonidine and BS 100-141 on the EEG sleep pattern in rats.", "content": "The effects of the peripheral and central alpha-adrenoceptor stimulant and antihypertensive agents clonidine and BS 100-141 (N-amidino-2[2,6-dichlorophenyl]acetamide - HCl) on EEG sleep patterns in rats and on blood pressure in pithed rats have been investigated. Whereas both compounds abolished paradoxical sleep (PS), clonidine, in contrast to BS 100-141, markedly increased the sleeping time. Both drugs caused a dose-dependent increase in the blood pressure of pithed rats. The pressor action was abolished by the alpha-adrenoceptor blocking agent phentolamine, but was not influenced by reserpine, indicating a direct stimulation of vascular alpha-adrenoceptors by both drugs. It is suggested that sedation or sleep induction by adrenergic drugs cannot be explained exclusively by an action on central alpha-adrenoceptors. Rather, the findings suggest that such an action may be involved in the modulation of PS.", "contents": "Effects of clonidine and BS 100-141 on the EEG sleep pattern in rats. The effects of the peripheral and central alpha-adrenoceptor stimulant and antihypertensive agents clonidine and BS 100-141 (N-amidino-2[2,6-dichlorophenyl]acetamide - HCl) on EEG sleep patterns in rats and on blood pressure in pithed rats have been investigated. Whereas both compounds abolished paradoxical sleep (PS), clonidine, in contrast to BS 100-141, markedly increased the sleeping time. Both drugs caused a dose-dependent increase in the blood pressure of pithed rats. The pressor action was abolished by the alpha-adrenoceptor blocking agent phentolamine, but was not influenced by reserpine, indicating a direct stimulation of vascular alpha-adrenoceptors by both drugs. It is suggested that sedation or sleep induction by adrenergic drugs cannot be explained exclusively by an action on central alpha-adrenoceptors. Rather, the findings suggest that such an action may be involved in the modulation of PS."}
{"id": "PMID:240729", "title": "Effects of adrenergic drugs on sheep oviduct motility.", "content": "Recordings of electrical activity of the oviduct in conscious ewes fitted with an extracellular multi-electrode assembly confirm the presence of alpha- and beta-adrenergic receptors in both the ampullary and isthmic portions. Regional differences in response to noradrenaline and isoprenaline were observed particularly during oestrus. In all cases the lowest threshold of sensitivity was exhibited by the isthmic portion of the oviduct.", "contents": "Effects of adrenergic drugs on sheep oviduct motility. Recordings of electrical activity of the oviduct in conscious ewes fitted with an extracellular multi-electrode assembly confirm the presence of alpha- and beta-adrenergic receptors in both the ampullary and isthmic portions. Regional differences in response to noradrenaline and isoprenaline were observed particularly during oestrus. In all cases the lowest threshold of sensitivity was exhibited by the isthmic portion of the oviduct."}
{"id": "PMID:240730", "title": "Potent alpha-adrenoceptor action of soterenol on vascular and other smooth muscle.", "content": "Treatment with soterenol (0.3-300 mug/kg, i.v.) increased the mean arterial blood pressure and decreased heart rate in rabbits. Soterenol caused a dose-dependent contraction of rabbit aorta and portal vein, guinea-pig vas deferens and cat nicitating membrane which was inhibited by phentolamine. Other beta-agonists such as isoproterenol, salbutamol and terbutaline did not exhibit similar effects. Soterenol had potent stimulant action on the alpha-receptor of the smooth muscle.", "contents": "Potent alpha-adrenoceptor action of soterenol on vascular and other smooth muscle. Treatment with soterenol (0.3-300 mug/kg, i.v.) increased the mean arterial blood pressure and decreased heart rate in rabbits. Soterenol caused a dose-dependent contraction of rabbit aorta and portal vein, guinea-pig vas deferens and cat nicitating membrane which was inhibited by phentolamine. Other beta-agonists such as isoproterenol, salbutamol and terbutaline did not exhibit similar effects. Soterenol had potent stimulant action on the alpha-receptor of the smooth muscle."}
{"id": "PMID:240731", "title": "Apomorphine-like effect of an aminotetralin on the linguomandibular reflex of the cat.", "content": "Low doses of 5,6-dihydroxy-2-dimethylaminotetralin (M-7) produced inhibition of the linguomandibular reflex in the cat. This inhibition was similar to that produced by apomorphine and was blocked by haloperidol, bulbocapnine or chlorpromazine. M-7 also had a brief but marked hypertensive effect. Gradual bradycardia also developed. These results indicate that M-7 inhibits the linguomandibular reflex by interaction at dopamine receptors, or 'apomorphine' receptors.", "contents": "Apomorphine-like effect of an aminotetralin on the linguomandibular reflex of the cat. Low doses of 5,6-dihydroxy-2-dimethylaminotetralin (M-7) produced inhibition of the linguomandibular reflex in the cat. This inhibition was similar to that produced by apomorphine and was blocked by haloperidol, bulbocapnine or chlorpromazine. M-7 also had a brief but marked hypertensive effect. Gradual bradycardia also developed. These results indicate that M-7 inhibits the linguomandibular reflex by interaction at dopamine receptors, or 'apomorphine' receptors."}
{"id": "PMID:240732", "title": "Alterations in graft--ersus-host reactivity and peripheral leukocytes in mice after erythropoietin treatment.", "content": "Treatment of mice on four consecutive days with either erythropoietin (EP) or rabbit antimouse thymocyte serum (ATS) resulted in a significant reduction in antigenic reactivity of spleen cells as measured by the Simonsen assay. In normal animals, treatment with either EP or ATS resulted in lymphopenia and in most instances a neutrophilia and a variable monocytopenia. Similar alterations in these cell types were recorded for polycythemic mice subsequent to treatment with either EP or ATS. These data plus histologic analyses support the idea that there is an inverse relationship between the cells committed to differentiate along the lymphoid cell line and the cells committed to differentiate along myeloid cell lines. Further, the data are consistent with the \"carrying capacity\" concept regarding the stem cell microenvironment and support the monophyletic theory.", "contents": "Alterations in graft--ersus-host reactivity and peripheral leukocytes in mice after erythropoietin treatment. Treatment of mice on four consecutive days with either erythropoietin (EP) or rabbit antimouse thymocyte serum (ATS) resulted in a significant reduction in antigenic reactivity of spleen cells as measured by the Simonsen assay. In normal animals, treatment with either EP or ATS resulted in lymphopenia and in most instances a neutrophilia and a variable monocytopenia. Similar alterations in these cell types were recorded for polycythemic mice subsequent to treatment with either EP or ATS. These data plus histologic analyses support the idea that there is an inverse relationship between the cells committed to differentiate along the lymphoid cell line and the cells committed to differentiate along myeloid cell lines. Further, the data are consistent with the \"carrying capacity\" concept regarding the stem cell microenvironment and support the monophyletic theory."}
{"id": "PMID:240734", "title": "Presence of a specific uridine 5'-monophosphate pyrophosphorylase in baker's yeast.", "content": "Uridine 5'-monophosphate pyrophosphorylase was found to be present in baker's yeast. The enzyme preparation, purified about 30-fold, shows a strict specificity toward uracil and requires Mg++ for its activity.", "contents": "Presence of a specific uridine 5'-monophosphate pyrophosphorylase in baker's yeast. Uridine 5'-monophosphate pyrophosphorylase was found to be present in baker's yeast. The enzyme preparation, purified about 30-fold, shows a strict specificity toward uracil and requires Mg++ for its activity."}
{"id": "PMID:240736", "title": "Chemical excitability of axons: excitatory and inhibititory effects of putative neurotransmitters and modulators on frog sciatic nerves.", "content": "The microiontophoretic administration of putative neuromodulators (acetylcholine, norepinephrine, dopamine, 2-phenylethylamine, tryptamine, histamine) triggered firing or inhibited on-going activity in isolated frog sciatic nerves.", "contents": "Chemical excitability of axons: excitatory and inhibititory effects of putative neurotransmitters and modulators on frog sciatic nerves. The microiontophoretic administration of putative neuromodulators (acetylcholine, norepinephrine, dopamine, 2-phenylethylamine, tryptamine, histamine) triggered firing or inhibited on-going activity in isolated frog sciatic nerves."}
{"id": "PMID:240738", "title": "[Some new derivatives of aromatic oximes with beta-blocking activity].", "content": "Because of the great importance assumed by beta-blocking agents in recent years, some new derivatives of aromatic oxime ethers, in the syn form, have been synthesized, having the following general structure: The above compounds were obtained by two different methods designed to demonstrate their structure. The results of some pharmacological tests are also reported, in order to give an indication of the real activity of the new compounds synthesized.", "contents": "[Some new derivatives of aromatic oximes with beta-blocking activity]. Because of the great importance assumed by beta-blocking agents in recent years, some new derivatives of aromatic oxime ethers, in the syn form, have been synthesized, having the following general structure: The above compounds were obtained by two different methods designed to demonstrate their structure. The results of some pharmacological tests are also reported, in order to give an indication of the real activity of the new compounds synthesized."}
{"id": "PMID:240741", "title": "Metabolic factors in peripheral circulatory regulation.", "content": "The old and recent literature bearing on the role of metabolic factors in exercise hyperemia has been reviewed. Two general conclusions have gradually emerged over the years. First, no one factor is by itself a sufficient explanation for the hyperemia. Second, the contributions of the various factors appear to change with time of exercise. While additional temporal studies are needed to firmly establish more specific conclusions, those now available suggest that factors related to skeletal muscle cell depolarization initiate the hyperemia while factors related to oxygen consumption in excess of oxygen delivery contribute more to the maintenance of the hyperemia. For example, the potassium that leaves the skeletal muscle cell on depolarization appears to contribute more to the initiation of the hyperemia than to its maintenance. Hydrogen, on the other hand, appears to have little to do with initiation but may contribute to maintenance, at least with grades of exercise that reduce cellular oxygen tension. The picture that emerges from the review seems to be one of multiple factors acting in concert with a changing temporal pattern.", "contents": "Metabolic factors in peripheral circulatory regulation. The old and recent literature bearing on the role of metabolic factors in exercise hyperemia has been reviewed. Two general conclusions have gradually emerged over the years. First, no one factor is by itself a sufficient explanation for the hyperemia. Second, the contributions of the various factors appear to change with time of exercise. While additional temporal studies are needed to firmly establish more specific conclusions, those now available suggest that factors related to skeletal muscle cell depolarization initiate the hyperemia while factors related to oxygen consumption in excess of oxygen delivery contribute more to the maintenance of the hyperemia. For example, the potassium that leaves the skeletal muscle cell on depolarization appears to contribute more to the initiation of the hyperemia than to its maintenance. Hydrogen, on the other hand, appears to have little to do with initiation but may contribute to maintenance, at least with grades of exercise that reduce cellular oxygen tension. The picture that emerges from the review seems to be one of multiple factors acting in concert with a changing temporal pattern."}
{"id": "PMID:240742", "title": "Differences in hepatic and metabolic changes after acute and chronic alcohol consumption.", "content": "Hepatic metabolism of ethanol to acetaldehyde by the alcohol dehydrogenase pathway is associated with the generation of reducing equivalents as NADH. Conversely, reducing equivalents are consumed when ethanol oxidation is catalyzed by the NADPH dependent microsomal ethanol oxidizing system. Since the major fraction of ethanol metabolism proceeds via alcohol dehydrogenase and since the oxidation of acetaldehyde also generates NADH, an excess of reducing equivalents is produced. This explains a variety of effects following acute ethanol administration, including hyperlactacidemia, hyperuricemia, enhanced lipogenesis and depressed lipid oxidation. To the extent that ethanol is oxidized by the alternate microsomal ethanol oxidizing system pathway, it slows the metabolism of other microsomal substrates. Following chronic ethanol consumption, adaptive microsomal changes prevail, which include enhanced ethanol and drug metabolism, and increased lipoprotein production. Severe hepatic lesions (alcoholic hepatitis and cirrhosis) develop after prolonged ethanol consumption in baboons. These injurious alterations are not prevented by nutritionally adequate diets and can therefore be ascribed to ethanol rather than to dietary inadequacy.", "contents": "Differences in hepatic and metabolic changes after acute and chronic alcohol consumption. Hepatic metabolism of ethanol to acetaldehyde by the alcohol dehydrogenase pathway is associated with the generation of reducing equivalents as NADH. Conversely, reducing equivalents are consumed when ethanol oxidation is catalyzed by the NADPH dependent microsomal ethanol oxidizing system. Since the major fraction of ethanol metabolism proceeds via alcohol dehydrogenase and since the oxidation of acetaldehyde also generates NADH, an excess of reducing equivalents is produced. This explains a variety of effects following acute ethanol administration, including hyperlactacidemia, hyperuricemia, enhanced lipogenesis and depressed lipid oxidation. To the extent that ethanol is oxidized by the alternate microsomal ethanol oxidizing system pathway, it slows the metabolism of other microsomal substrates. Following chronic ethanol consumption, adaptive microsomal changes prevail, which include enhanced ethanol and drug metabolism, and increased lipoprotein production. Severe hepatic lesions (alcoholic hepatitis and cirrhosis) develop after prolonged ethanol consumption in baboons. These injurious alterations are not prevented by nutritionally adequate diets and can therefore be ascribed to ethanol rather than to dietary inadequacy."}
{"id": "PMID:240743", "title": "Significant pathways of hepatic ethanol metabolism.", "content": "Rat liver microsomes oxidized ethanol two to three times faster than propanol when incubated with either an NADPH- or an H2O2-generating system. In addition, solubilized, purified microsomal subfractions were found to contain protein with an electrophoretic mobility identical to rat liver catalase on SDS polyacrylamide gels, suggesting that the separation of catalase from cytochrome P-450 and other microsomal components may not be feasible. These data support the postulate that catalase is responsible for NADPH-dependent microsomal ethanol oxidation. Direct read-out techniques for pyridine nucleotides, the catalase-H2O2 complex, and cytochrome P-450 were utilized to evaluate the specificity of inhibitors of alcohol dehydrogenase (4-methylpyrazole; 4 mM) and catalase (aminotriazole; 1.0 g/kg) qualitatively in perfused rat livers. 4-Methylpyrazole and aminotriazole are specific inhibitors for alcohol dehydrogenase and catalase, respectively, under these conditions. Neither inhibitor nor a combination of them altered the mixed function oxygen of p-nitroanisole to p-nitrophenol as observed by oxygen uptake and product formation. When ethanol utilization was measured over the concentration range 20-80 mM in perfused liver, a concentration dependence was observed. At low concentrations of ethanol, ethanol oxidation was almost totally abolished by 4-methylpyrazole; however, the contribution of 4-methylpyrazole-insensitive ethanol uptake increased as a function of ethanol concentration. At 80 mM ethanol, ethanol utilization was nearly 50% methylpyrazole-insensitive. This portion of ethanol oxidation, however, was abolished by aminotriazole. The data indicate that alcohol dehydrogenase and catalase-H2O2 are responsible for hepatic ethanol oxidation. At low ethanol concentrations (less than 20 mM), alcohol dehydrogenase is predominant; however, at higher ethanol concentrations (up to 80 mM), the contribution of catalase-H2O2 to overall ethanol utilization is significant. No evidence that the endoplasmic reticulum is involved in ethanol metabolism in the perfused liver emerged from these studies.", "contents": "Significant pathways of hepatic ethanol metabolism. Rat liver microsomes oxidized ethanol two to three times faster than propanol when incubated with either an NADPH- or an H2O2-generating system. In addition, solubilized, purified microsomal subfractions were found to contain protein with an electrophoretic mobility identical to rat liver catalase on SDS polyacrylamide gels, suggesting that the separation of catalase from cytochrome P-450 and other microsomal components may not be feasible. These data support the postulate that catalase is responsible for NADPH-dependent microsomal ethanol oxidation. Direct read-out techniques for pyridine nucleotides, the catalase-H2O2 complex, and cytochrome P-450 were utilized to evaluate the specificity of inhibitors of alcohol dehydrogenase (4-methylpyrazole; 4 mM) and catalase (aminotriazole; 1.0 g/kg) qualitatively in perfused rat livers. 4-Methylpyrazole and aminotriazole are specific inhibitors for alcohol dehydrogenase and catalase, respectively, under these conditions. Neither inhibitor nor a combination of them altered the mixed function oxygen of p-nitroanisole to p-nitrophenol as observed by oxygen uptake and product formation. When ethanol utilization was measured over the concentration range 20-80 mM in perfused liver, a concentration dependence was observed. At low concentrations of ethanol, ethanol oxidation was almost totally abolished by 4-methylpyrazole; however, the contribution of 4-methylpyrazole-insensitive ethanol uptake increased as a function of ethanol concentration. At 80 mM ethanol, ethanol utilization was nearly 50% methylpyrazole-insensitive. This portion of ethanol oxidation, however, was abolished by aminotriazole. The data indicate that alcohol dehydrogenase and catalase-H2O2 are responsible for hepatic ethanol oxidation. At low ethanol concentrations (less than 20 mM), alcohol dehydrogenase is predominant; however, at higher ethanol concentrations (up to 80 mM), the contribution of catalase-H2O2 to overall ethanol utilization is significant. No evidence that the endoplasmic reticulum is involved in ethanol metabolism in the perfused liver emerged from these studies."}
{"id": "PMID:240756", "title": "Action of metiamide on the lower esophageal sphincter.", "content": "The action of metiamide, an H2 antagonist, was tested for its effect upon lower esophageal sphincter (LES) function in the anesthetized opossum. Intravenous infusions of metiamide gave a dose-related increase in LES pressure. A maximum increase in pressure of 17 mm Hg was attained at 2.0 mg per kg-hr of metiamide. This dose of metiamide abolished acid secretion in response to gastrin I, but augmented the maximal LES response to this hormone. Studies in vitro showed that metiamide augmented the maximal LES muscle responses to gastrin I or histamine but had no effect on other agonist responses. Metiamide alone did not alter LES muscle tension. An inhibitory response to gastrin I or histamine could be demonstrated in the presence of atropine or diphenhydramine, respectively, on muscle which had first been depolarized with KCl. These inhibitory responses were antagonized by metiamide. These studies indicate that metiamide: (a) increases LES pressure; (b) selectively augments LES muscle excitatory responses to gastrin I or histamine; and (c) selectively antagonizes inhibitory muscle responses to histamine or gastrin I.", "contents": "Action of metiamide on the lower esophageal sphincter. The action of metiamide, an H2 antagonist, was tested for its effect upon lower esophageal sphincter (LES) function in the anesthetized opossum. Intravenous infusions of metiamide gave a dose-related increase in LES pressure. A maximum increase in pressure of 17 mm Hg was attained at 2.0 mg per kg-hr of metiamide. This dose of metiamide abolished acid secretion in response to gastrin I, but augmented the maximal LES response to this hormone. Studies in vitro showed that metiamide augmented the maximal LES muscle responses to gastrin I or histamine but had no effect on other agonist responses. Metiamide alone did not alter LES muscle tension. An inhibitory response to gastrin I or histamine could be demonstrated in the presence of atropine or diphenhydramine, respectively, on muscle which had first been depolarized with KCl. These inhibitory responses were antagonized by metiamide. These studies indicate that metiamide: (a) increases LES pressure; (b) selectively augments LES muscle excitatory responses to gastrin I or histamine; and (c) selectively antagonizes inhibitory muscle responses to histamine or gastrin I."}
{"id": "PMID:240757", "title": "Fate of ingested hepatitis B antigen in blood-sucking insects.", "content": "The fate of ingested hepatitis B antigen (HBsAg) in two mosquito species and two Hemiptera species was compared with the rate of blood meal digestion by these insects. In both mosquito species HBsAg was detected by radioimmunoassay for only a few hours after ingestion, disappearing well before the time of blood meal digestion. Production of a protease by the mosquito midgut may have been responsible for destruction of the antigen. In contrast, in the bedbug HBsAg remained detectable throughout a 5-week testing period. Moreover, titers rose during the last week, when blood meal digestion was complete, suggesting possible replication of the antigen. At no time was antigen detected in eggs or feces of any species tested, but juvenile bedbugs fed HBsAg when in the fourth or fifth instar stage still contained antigen after molting. These studies suggest that bedbugs may potentially be a more dangerous source of hepatitis B transmission than mosquitoes.", "contents": "Fate of ingested hepatitis B antigen in blood-sucking insects. The fate of ingested hepatitis B antigen (HBsAg) in two mosquito species and two Hemiptera species was compared with the rate of blood meal digestion by these insects. In both mosquito species HBsAg was detected by radioimmunoassay for only a few hours after ingestion, disappearing well before the time of blood meal digestion. Production of a protease by the mosquito midgut may have been responsible for destruction of the antigen. In contrast, in the bedbug HBsAg remained detectable throughout a 5-week testing period. Moreover, titers rose during the last week, when blood meal digestion was complete, suggesting possible replication of the antigen. At no time was antigen detected in eggs or feces of any species tested, but juvenile bedbugs fed HBsAg when in the fourth or fifth instar stage still contained antigen after molting. These studies suggest that bedbugs may potentially be a more dangerous source of hepatitis B transmission than mosquitoes."}
{"id": "PMID:240760", "title": "Production of alkaloids and differentiation in a submerged culture of Claviceps purpurea (Fr.) Tul.", "content": "The submerged culture of the Claviceps purpurea strain studied was polymorphous. In the process of alkaloid synthesis, cytodifferentiation preceded biochemical differentiation. The onset of the alkaloid phase was characterized by: predominance of chlamydospores in the culture, the presence of vegetative cells with reduced or arrested proliferation, maximum acetylCoA carboxylase activity, the maximum amount of total fatty acids, an over-average cell pool tryptophan level and minimum tryptophan synthetase activity. Intracellular ricinoleic acid was an indicator of differentiation of the culture towards alkaloid formation and also of alkaloid synthesis. The cytodifferentiation period in the initial phases of fermentation, when the cell has several alternative possibilities of development, is regarded as the most sensitive sector of the regulatory mechanisms of alkaloid formation.", "contents": "Production of alkaloids and differentiation in a submerged culture of Claviceps purpurea (Fr.) Tul. The submerged culture of the Claviceps purpurea strain studied was polymorphous. In the process of alkaloid synthesis, cytodifferentiation preceded biochemical differentiation. The onset of the alkaloid phase was characterized by: predominance of chlamydospores in the culture, the presence of vegetative cells with reduced or arrested proliferation, maximum acetylCoA carboxylase activity, the maximum amount of total fatty acids, an over-average cell pool tryptophan level and minimum tryptophan synthetase activity. Intracellular ricinoleic acid was an indicator of differentiation of the culture towards alkaloid formation and also of alkaloid synthesis. The cytodifferentiation period in the initial phases of fermentation, when the cell has several alternative possibilities of development, is regarded as the most sensitive sector of the regulatory mechanisms of alkaloid formation."}
{"id": "PMID:240761", "title": "Effect of boseimycin on some enzyme systems of Bacillus subtilis.", "content": "The effect of boseimycin on the in vitro activity and in vivo synthesis of alkaline phosphatase, aconitase and lactate, isocitrate, glutamate and alanine dehydrogenases was studied in Bacillus subtilis. At a subinhibitory concentration, synthesis of glutamate dehydrogenase was stimulated but alkaline phosphatase, lactate dehydrogenase and aconitase synthesis was inhibited. On the contrary, boseimycin inhibited slightly the activity of lactate dehydrogenase in cell-free extracts. Glutamate dehydrogenase and aconitase activities were not affected.", "contents": "Effect of boseimycin on some enzyme systems of Bacillus subtilis. The effect of boseimycin on the in vitro activity and in vivo synthesis of alkaline phosphatase, aconitase and lactate, isocitrate, glutamate and alanine dehydrogenases was studied in Bacillus subtilis. At a subinhibitory concentration, synthesis of glutamate dehydrogenase was stimulated but alkaline phosphatase, lactate dehydrogenase and aconitase synthesis was inhibited. On the contrary, boseimycin inhibited slightly the activity of lactate dehydrogenase in cell-free extracts. Glutamate dehydrogenase and aconitase activities were not affected."}
{"id": "PMID:240762", "title": "Regulation of biosynthesis of secondary metabolites. XVII. Purification and properties of malate dehydrogenase (decarboxylating) in Streptomyces aureofaciens.", "content": "The process of isolation and purification of malate dehydrogenase (decarboxylating) (EC 1.1.1.40) from the mycelium of the actinomycete Streptomyces aureofaciens has been worked out. The enzyme was purified 35 fold. The kinetic characters of the purified enzyme are very similar to the figures for malate dehydrogenase (decarboxylating) from other sources. Km for L-malate = 2.1 X 10(-3)M, Km for NADP = 4.6 X 10(-5)M (at pH 7.4). The reaction requires metal divalent ions, Mn2+ being more effective than Mg2+. The enzyme reaches its maximal activity at pH 8.75.", "contents": "Regulation of biosynthesis of secondary metabolites. XVII. Purification and properties of malate dehydrogenase (decarboxylating) in Streptomyces aureofaciens. The process of isolation and purification of malate dehydrogenase (decarboxylating) (EC 1.1.1.40) from the mycelium of the actinomycete Streptomyces aureofaciens has been worked out. The enzyme was purified 35 fold. The kinetic characters of the purified enzyme are very similar to the figures for malate dehydrogenase (decarboxylating) from other sources. Km for L-malate = 2.1 X 10(-3)M, Km for NADP = 4.6 X 10(-5)M (at pH 7.4). The reaction requires metal divalent ions, Mn2+ being more effective than Mg2+. The enzyme reaches its maximal activity at pH 8.75."}
{"id": "PMID:240763", "title": "Protease activity in cells of Bacillus megaterium during derepression.", "content": "A proteolytic activity hydrolyzing denatured proteins of Bacillus megaterium labelled with 35S or 14C amino acids was detected in cells of the asporogenic strain of Bacillus megaterium. The substrate is hydrolyzed by the enzyme or enzymes at optimum pH around 7, their activity being almost completely inhibited by EDTA and o-phenanthroline. PMSF, the inhibitor of serine proteases, is slightly inhibitory. Gel filtration on a Sephadex column separated the protease activity to two or three fractions. The protease activity in cells with the repressed synthesis of protease corresponds to 5-20 mug of substrate degraded per hour by 1 mg of protein at 37 degrees C. It increases five to ten-fold during the derepression. When the intracellular protease activity increases the extracellular enzyme begins to be excreted into the medium. The intracellular protease activity rapidly decreases after the addition of chloramphenicol or of a mixture of amino acids to the derepressed culture. Half or even more of the protease activity is released from the cells during their conversion to protoplasts by means of lysozyme. This \"periplasmic\" activity remains mostly in the supernatant also after mesosomes have been centrifuged down from the periplasm. A portion of the activity bound in protoplasts sediments together with membrane fraction after their lysis.", "contents": "Protease activity in cells of Bacillus megaterium during derepression. A proteolytic activity hydrolyzing denatured proteins of Bacillus megaterium labelled with 35S or 14C amino acids was detected in cells of the asporogenic strain of Bacillus megaterium. The substrate is hydrolyzed by the enzyme or enzymes at optimum pH around 7, their activity being almost completely inhibited by EDTA and o-phenanthroline. PMSF, the inhibitor of serine proteases, is slightly inhibitory. Gel filtration on a Sephadex column separated the protease activity to two or three fractions. The protease activity in cells with the repressed synthesis of protease corresponds to 5-20 mug of substrate degraded per hour by 1 mg of protein at 37 degrees C. It increases five to ten-fold during the derepression. When the intracellular protease activity increases the extracellular enzyme begins to be excreted into the medium. The intracellular protease activity rapidly decreases after the addition of chloramphenicol or of a mixture of amino acids to the derepressed culture. Half or even more of the protease activity is released from the cells during their conversion to protoplasts by means of lysozyme. This \"periplasmic\" activity remains mostly in the supernatant also after mesosomes have been centrifuged down from the periplasm. A portion of the activity bound in protoplasts sediments together with membrane fraction after their lysis."}
{"id": "PMID:240764", "title": "Studies on methanol - oxidizing yeast. III. Enzyme.", "content": "Oxidation of methanol, formaldehyde and formic acid was studied in cells and cell-free extract of the yeast Candida boidinii No. 11Bh. Methanol oxidase, an enzyme oxidizing methanol to formaldehyde, was formed inducibly after the addition of methanol to yeast cells. The oxidation of methanol by cell-free extract was dependent on the presence of oxygen and independent of any addition of nicotine-amide nucleotides. Temperature optimum for the oxidation of methanol to formaldehyde was 35 degrees C, pH optimum was 8.5. The Km for methanol was 0.8mM. The cell-free extract exhibited a broad substrate specificity towards primary alcohols (C1--C6). The activity of methanol oxidase was not inhibited by 1mM KCN, EDTA or monoiodoacetic acid. The strongest inhibitory action was exerted by p-chloromercuribenzoate. Both the cells and the cell-free extract contained catalase which participated in the oxidation of methanol to formaldehyde; the enzyme was constitutively formed by the yeast. The pH optimum for the degradation of H2O2 was in the same range as the optimum for methanol oxidation, viz. at 8.5. Catalase was more resistant to high pH than methanol oxidase. The cell-free extract contained also GSH-dependent NAD-formaldehyde dehydrogenase with Km = 0.29mM and NAD-formate dehydrogenase with Km = 55mM.", "contents": "Studies on methanol - oxidizing yeast. III. Enzyme. Oxidation of methanol, formaldehyde and formic acid was studied in cells and cell-free extract of the yeast Candida boidinii No. 11Bh. Methanol oxidase, an enzyme oxidizing methanol to formaldehyde, was formed inducibly after the addition of methanol to yeast cells. The oxidation of methanol by cell-free extract was dependent on the presence of oxygen and independent of any addition of nicotine-amide nucleotides. Temperature optimum for the oxidation of methanol to formaldehyde was 35 degrees C, pH optimum was 8.5. The Km for methanol was 0.8mM. The cell-free extract exhibited a broad substrate specificity towards primary alcohols (C1--C6). The activity of methanol oxidase was not inhibited by 1mM KCN, EDTA or monoiodoacetic acid. The strongest inhibitory action was exerted by p-chloromercuribenzoate. Both the cells and the cell-free extract contained catalase which participated in the oxidation of methanol to formaldehyde; the enzyme was constitutively formed by the yeast. The pH optimum for the degradation of H2O2 was in the same range as the optimum for methanol oxidation, viz. at 8.5. Catalase was more resistant to high pH than methanol oxidase. The cell-free extract contained also GSH-dependent NAD-formaldehyde dehydrogenase with Km = 0.29mM and NAD-formate dehydrogenase with Km = 55mM."}
{"id": "PMID:240765", "title": "Transport of acyclic polyols in Saccharomyces cerevisiae.", "content": "Acyclic polyols (erythritol, xylitol, ribitol, D-arabinitol, mannitol, sorbitol and galactitol) are not metabolized by Saccharomyces cerevisiae. They are taken up by a fast non-active process, reaching 40-70% distribution referred to total cell water. The uptake is insensitive to temperature, pH (between 4 and 8), 2,4-dinitrophenol and uranyl ions. Its initial rate rises linearly with concentration from 10(-5)M to 1M. The process resembles simple diffusion through large pores or the trapping of the whole solution on the surface. Protoplasts behave like whole cells in this respect. Only erythritol shows a second type of uptake which is inhibitor-insensitive but temperature-dependent.", "contents": "Transport of acyclic polyols in Saccharomyces cerevisiae. Acyclic polyols (erythritol, xylitol, ribitol, D-arabinitol, mannitol, sorbitol and galactitol) are not metabolized by Saccharomyces cerevisiae. They are taken up by a fast non-active process, reaching 40-70% distribution referred to total cell water. The uptake is insensitive to temperature, pH (between 4 and 8), 2,4-dinitrophenol and uranyl ions. Its initial rate rises linearly with concentration from 10(-5)M to 1M. The process resembles simple diffusion through large pores or the trapping of the whole solution on the surface. Protoplasts behave like whole cells in this respect. Only erythritol shows a second type of uptake which is inhibitor-insensitive but temperature-dependent."}
{"id": "PMID:240766", "title": "[Studies on the reaction mechanism of a ribonuclease II from Aspergillus oryzae (author's transl)].", "content": "Ribonuclease T2 was isolated from an Aspergillus oryzae extract. In order to define the substrate specificity, the hydrolysis of a series of 2',3'-cyclic nucleotides was measured semiquantitatively. Modifications in all positions of the bases are tolerated, as long as the base stays in the anti conformation or has a chance to return to it; bulky substituents at N-3 of the pyrimidine base lower the rate. So far the conclusion seems justified that the enzyme does not react with the substrates by specific bonds to the base, but rather by hydrophobic binding. The conformation specificity and the pH dependence of the activity support this hypothesis. The pH optima with substrates which may be positively or negatively charged are shifted to pH values at which the substrates are uncharged. This strongly indicates a hydrophobic type of interaction between base and enzyme. From the pH dependence of the kinetic parameters Km and k+2, an enzyme group with a pK of 7 (probably histidine) can be postulated. This group should interact in the protonated form with the phosphate anion. Another B.HB-system (probably two carboxylate groups) seems to be involved in the catalysis step, performing the base catalysis at the 2'-OH group and the proton catalysis at the phosphate oxygen simultaneously.", "contents": "[Studies on the reaction mechanism of a ribonuclease II from Aspergillus oryzae (author's transl)]. Ribonuclease T2 was isolated from an Aspergillus oryzae extract. In order to define the substrate specificity, the hydrolysis of a series of 2',3'-cyclic nucleotides was measured semiquantitatively. Modifications in all positions of the bases are tolerated, as long as the base stays in the anti conformation or has a chance to return to it; bulky substituents at N-3 of the pyrimidine base lower the rate. So far the conclusion seems justified that the enzyme does not react with the substrates by specific bonds to the base, but rather by hydrophobic binding. The conformation specificity and the pH dependence of the activity support this hypothesis. The pH optima with substrates which may be positively or negatively charged are shifted to pH values at which the substrates are uncharged. This strongly indicates a hydrophobic type of interaction between base and enzyme. From the pH dependence of the kinetic parameters Km and k+2, an enzyme group with a pK of 7 (probably histidine) can be postulated. This group should interact in the protonated form with the phosphate anion. Another B.HB-system (probably two carboxylate groups) seems to be involved in the catalysis step, performing the base catalysis at the 2'-OH group and the proton catalysis at the phosphate oxygen simultaneously."}
{"id": "PMID:240767", "title": "Studies on a 2,3-diaminopropionate: ammonia-lyase from a Pseudomonad.", "content": "2,3-Diaminopropionate:ammonia-lyase, an induced enzyme in a Pseudomonas isolate, has been purified 40-fold and found to be homogeneous by disc gel electrophoresis and by ultracentrifugation. Some of its properties have been studied. The optimum pH and temperature for activity are 8 and 40 degrees C, respectively. The enzyme shows a high degree of substrate specificity, acting only on 2,3-diaminopropionate; the D-isomer is only one-eighth as effective as the L-form. L-Homoserine and DL-cystathionine are not substrates, and 3-cyanolalanine does not inhibit its activity. It is a pyridoxal phosphate enzyme which requires free enzyme sulphhydryls for activity. The Km values for L-2,3-diaminopropionate and pyridoxal phosphate are 1mM and 25 muM, respectively. The molecular weight of the enzyme is about 80 000 as determined by gel filtration. On treatment with 0.5M urea or guanidine by hydrochloride, the enzyme dissociates into inactive subunits with an approximate molecular weight of 45 000. One mole of the active enzyme binds one mole of pyridoxal phosphate. The bacterial enzyme seems to be quite different in many of its properties from the rat liver enzyme which also exhibits the substrate specificity of cystathionine gamma-lyase.", "contents": "Studies on a 2,3-diaminopropionate: ammonia-lyase from a Pseudomonad. 2,3-Diaminopropionate:ammonia-lyase, an induced enzyme in a Pseudomonas isolate, has been purified 40-fold and found to be homogeneous by disc gel electrophoresis and by ultracentrifugation. Some of its properties have been studied. The optimum pH and temperature for activity are 8 and 40 degrees C, respectively. The enzyme shows a high degree of substrate specificity, acting only on 2,3-diaminopropionate; the D-isomer is only one-eighth as effective as the L-form. L-Homoserine and DL-cystathionine are not substrates, and 3-cyanolalanine does not inhibit its activity. It is a pyridoxal phosphate enzyme which requires free enzyme sulphhydryls for activity. The Km values for L-2,3-diaminopropionate and pyridoxal phosphate are 1mM and 25 muM, respectively. The molecular weight of the enzyme is about 80 000 as determined by gel filtration. On treatment with 0.5M urea or guanidine by hydrochloride, the enzyme dissociates into inactive subunits with an approximate molecular weight of 45 000. One mole of the active enzyme binds one mole of pyridoxal phosphate. The bacterial enzyme seems to be quite different in many of its properties from the rat liver enzyme which also exhibits the substrate specificity of cystathionine gamma-lyase."}
{"id": "PMID:240768", "title": "Subcellular distribution and properties of kynurenine pyruvate transaminase in rat kidney.", "content": "Kynurenine transaminase activity in rat kidney was found in both the mitochondrial and supernatant fractions. These fractions contained (a) kynurenine pyruvate transaminase, which showed a preference for pyruvate as amino acceptor, and had a pH optimum between 8.0 and 8.5, and (b) kynurenine 2-oxoglutarate transaminase, with a preference for 2-oxoglutarate and a pH optimum between 6.0 and 6.5. The apparent Km value of the former enzyme for L-kynurenine was much lower than that of the latter enzyme.", "contents": "Subcellular distribution and properties of kynurenine pyruvate transaminase in rat kidney. Kynurenine transaminase activity in rat kidney was found in both the mitochondrial and supernatant fractions. These fractions contained (a) kynurenine pyruvate transaminase, which showed a preference for pyruvate as amino acceptor, and had a pH optimum between 8.0 and 8.5, and (b) kynurenine 2-oxoglutarate transaminase, with a preference for 2-oxoglutarate and a pH optimum between 6.0 and 6.5. The apparent Km value of the former enzyme for L-kynurenine was much lower than that of the latter enzyme."}
{"id": "PMID:240769", "title": "[Glucosidases specific for the cyanogenic glucoside triglochinin. Purification and characterization of beta-glucosidases from Alocasia macrorrhiza Schott].", "content": "beta-Glucosidases have been isolated from Alocasia macrorrhiza plants. The enzymes are highly specific for the hydrolysis of the cyanogenic glucoside triglochinin endogenous to this plant. Upon chromatography of protein extracts on cation exchange resins and Sephadex G-200, separation into various enzymatically active bands was observed. The main fractions possess molecular weights of approximately 310000 and 105 000, as shown by preparative ultracentrifugation in a linear saccharose gradient. The beta-glucosidases are composed of subunits (molecular weight 55 000 to 60 000), as revealed by sodium dodecylsulfate gel electrophoresis. The result of alkaline disc electrophoresis and isoelectric focusing in polyacrylamide gel suggest that the beta-glucosidase fraction with molecular weight 105 000 is a dissociation product of the 310 000 molecular-weight species. The isoelectric points of the various beta-glocusidase bands, obtained by isoelectric focusing, vary between pH 4.5 and 5.0. The beta-glucosidases show a pronounced specificity for triglochinin. The Km for this substrate (3 times 10(-5) M) is 50 to 100-fold lower than for all other substrates hydrolyzed. Of the other cyanogenic glycosides, only those with an aromatic aglycone, (S)-configuration at the asymmetric carbon atom of the aglycone and glucose as sugar moiety were hydrolyzed to a measurable extent. The pH optimum of the enzyme reaction is 5.5, the temperature optimum around 50 degrees C. Cu2 ions and glucono-1,5-lactone inhibit beta-glucosidase activity approximately 50% at a concentration of 5 times 10(-4) M, while Hg2,Ag and p-chloromercuribenzoate show the same percent inhibition at 5 times 10(-7) M. Lipophilic solvents (ethanol, ethylene glycol monomethylether) activate the beta-glucosidase activity, preferentially by influencing the V values of the enzymes.", "contents": "[Glucosidases specific for the cyanogenic glucoside triglochinin. Purification and characterization of beta-glucosidases from Alocasia macrorrhiza Schott]. beta-Glucosidases have been isolated from Alocasia macrorrhiza plants. The enzymes are highly specific for the hydrolysis of the cyanogenic glucoside triglochinin endogenous to this plant. Upon chromatography of protein extracts on cation exchange resins and Sephadex G-200, separation into various enzymatically active bands was observed. The main fractions possess molecular weights of approximately 310000 and 105 000, as shown by preparative ultracentrifugation in a linear saccharose gradient. The beta-glucosidases are composed of subunits (molecular weight 55 000 to 60 000), as revealed by sodium dodecylsulfate gel electrophoresis. The result of alkaline disc electrophoresis and isoelectric focusing in polyacrylamide gel suggest that the beta-glucosidase fraction with molecular weight 105 000 is a dissociation product of the 310 000 molecular-weight species. The isoelectric points of the various beta-glocusidase bands, obtained by isoelectric focusing, vary between pH 4.5 and 5.0. The beta-glucosidases show a pronounced specificity for triglochinin. The Km for this substrate (3 times 10(-5) M) is 50 to 100-fold lower than for all other substrates hydrolyzed. Of the other cyanogenic glycosides, only those with an aromatic aglycone, (S)-configuration at the asymmetric carbon atom of the aglycone and glucose as sugar moiety were hydrolyzed to a measurable extent. The pH optimum of the enzyme reaction is 5.5, the temperature optimum around 50 degrees C. Cu2 ions and glucono-1,5-lactone inhibit beta-glucosidase activity approximately 50% at a concentration of 5 times 10(-4) M, while Hg2,Ag and p-chloromercuribenzoate show the same percent inhibition at 5 times 10(-7) M. Lipophilic solvents (ethanol, ethylene glycol monomethylether) activate the beta-glucosidase activity, preferentially by influencing the V values of the enzymes."}
{"id": "PMID:240770", "title": "Kinetic studies on microsomal glucose dehydrogenase in rat liver.", "content": "Glucose dehydrogenase from rat liver microsomes was found to react not only with glucose as a substrate but also with glucose 6-phosphate, 2-deoxyglucose 6-phosphate and galactose 6-phosphate. The relative maximum activity of this enzyme was 29% for glucose 6-phosphate, 99% for 2-deoxyglucose 6-phosphate, and 25% for galactose 6-phosphate, compared with 100% for glucose with NADP. The enzyme could utilize either NAD or NADP as a coenzyme. Using polyacrylamide gradient gel electrophoresis, we were able to detect several enzymatically active bands by incubation of the gels in a tetrazolium assay mixture. Each band had different Km values for the substrates (3.0 x 10(-5)M glucose 6-phosphate with NADP to 2.4M glucose with NAD) and for coenzymes (1.3 x 10(-6)M NAD with galactose 6-phosphate to 5.9 x 10(-5)M NAD with glucose). Though glucose 6-phosphate and galactose 6-phosphate reacted with glucose dehydrogenase, they inhibited the reaction of this enzyme only when either glucose or 2-deoxyglucose 6-phosphate was used as a substrate. The Ki values for glucose 6-phosphate with glucose as substrate were 4.0 x 10(-6)M with NAD, and 8.4 x 10(-6)M with NADP; for galactose 6-phosphate they were 6.7 x10(-6)M with NAD and 6.0 x 10(-6)M with NADP. The Ki values for glucose 6-phosphate with 2-deoxyglucose 6-phosphate as substrate were 6.3 x 10(-6)M with NAD and 8.9 x 10(-6)M with NADP; and for galactose 6-phosphate, 8.0 x 10(-6)M with NAD and 3.5 x 10(-6)M with NADP. Both NADH and NADPH inhibited glucose dehydrogenase when the corresponding oxidized coenzymes were used (Ki values: 8.0 x 10(-5)M by NADH and 9.1 x 10(-5)M by NADPH), while only NADPH inhibited cytoplasmic glucose 6-phosphate dehydrogenase (Ki: 2.4 x 10(-5)M). The results indicate that glucose dehydrogenase cannot directly oxidize glucose in vivo, but it might play a similar role to glucose 6-phosphate dehydrogenase. The differences in the kinetics of glucose dehydrogenase and glucose 6-phosphate dehydrogenase show that glucose 6-phosphate and galactose 6-phosphate could be metabolized in quite different ways in the microsomes and cytoplasm of rat liver.", "contents": "Kinetic studies on microsomal glucose dehydrogenase in rat liver. Glucose dehydrogenase from rat liver microsomes was found to react not only with glucose as a substrate but also with glucose 6-phosphate, 2-deoxyglucose 6-phosphate and galactose 6-phosphate. The relative maximum activity of this enzyme was 29% for glucose 6-phosphate, 99% for 2-deoxyglucose 6-phosphate, and 25% for galactose 6-phosphate, compared with 100% for glucose with NADP. The enzyme could utilize either NAD or NADP as a coenzyme. Using polyacrylamide gradient gel electrophoresis, we were able to detect several enzymatically active bands by incubation of the gels in a tetrazolium assay mixture. Each band had different Km values for the substrates (3.0 x 10(-5)M glucose 6-phosphate with NADP to 2.4M glucose with NAD) and for coenzymes (1.3 x 10(-6)M NAD with galactose 6-phosphate to 5.9 x 10(-5)M NAD with glucose). Though glucose 6-phosphate and galactose 6-phosphate reacted with glucose dehydrogenase, they inhibited the reaction of this enzyme only when either glucose or 2-deoxyglucose 6-phosphate was used as a substrate. The Ki values for glucose 6-phosphate with glucose as substrate were 4.0 x 10(-6)M with NAD, and 8.4 x 10(-6)M with NADP; for galactose 6-phosphate they were 6.7 x10(-6)M with NAD and 6.0 x 10(-6)M with NADP. The Ki values for glucose 6-phosphate with 2-deoxyglucose 6-phosphate as substrate were 6.3 x 10(-6)M with NAD and 8.9 x 10(-6)M with NADP; and for galactose 6-phosphate, 8.0 x 10(-6)M with NAD and 3.5 x 10(-6)M with NADP. Both NADH and NADPH inhibited glucose dehydrogenase when the corresponding oxidized coenzymes were used (Ki values: 8.0 x 10(-5)M by NADH and 9.1 x 10(-5)M by NADPH), while only NADPH inhibited cytoplasmic glucose 6-phosphate dehydrogenase (Ki: 2.4 x 10(-5)M). The results indicate that glucose dehydrogenase cannot directly oxidize glucose in vivo, but it might play a similar role to glucose 6-phosphate dehydrogenase. The differences in the kinetics of glucose dehydrogenase and glucose 6-phosphate dehydrogenase show that glucose 6-phosphate and galactose 6-phosphate could be metabolized in quite different ways in the microsomes and cytoplasm of rat liver."}
{"id": "PMID:240771", "title": "[B-chain shortening of matrix-bound insulin by pepsin, I:Preparation and properties of bovine des-pentapeptide(B26-30) insulin (suthor's transl)].", "content": "Insulin was adsorbed to a strongly acidic ion exchanger and incubated with pepsin. The digestion of the matrix-bound insulin was found to be restricted to the cleavage of the peptide bond between phenylalanine-B25 and tyrosine-B26. Factionation of the reaction products was achieved by gel filtrationon Sephadex G-50 at pH 8 where des-pentapeptide(B26-30)-insulin does not aggregate. Another way to purify this compound was ion-exchange chromatography, which was easy due to the loss of one positive charge on the modified insulin. Crystallization could be achieved in a phenol-containing buffer. Des-pentapeptide(B26-30)-insulin was found to be molecularly uniform by electrophoresis at pH 2.2 and 8.6, thin-layer chromatography, performic acid oxidation, end group analysis and amino acid analysis. The CD-spectrum indicated conformational changes compared to insulin. The biological activity was considerably reduced: fat cell assay 20%, blood sugar depression 30%.", "contents": "[B-chain shortening of matrix-bound insulin by pepsin, I:Preparation and properties of bovine des-pentapeptide(B26-30) insulin (suthor's transl)]. Insulin was adsorbed to a strongly acidic ion exchanger and incubated with pepsin. The digestion of the matrix-bound insulin was found to be restricted to the cleavage of the peptide bond between phenylalanine-B25 and tyrosine-B26. Factionation of the reaction products was achieved by gel filtrationon Sephadex G-50 at pH 8 where des-pentapeptide(B26-30)-insulin does not aggregate. Another way to purify this compound was ion-exchange chromatography, which was easy due to the loss of one positive charge on the modified insulin. Crystallization could be achieved in a phenol-containing buffer. Des-pentapeptide(B26-30)-insulin was found to be molecularly uniform by electrophoresis at pH 2.2 and 8.6, thin-layer chromatography, performic acid oxidation, end group analysis and amino acid analysis. The CD-spectrum indicated conformational changes compared to insulin. The biological activity was considerably reduced: fat cell assay 20%, blood sugar depression 30%."}
{"id": "PMID:240775", "title": "Glucose phosphate isomerase deficiency with hereditary hemolytic anemia in a Spanish family: clinical and familial studies.", "content": "A new case of glucose phosphate isomerase deficiency associated with cogenital nonspherocytic hemolytic anemia is described in a 12-year-old girl of Spanish origin. The parents exhibited erythrocyte glucose phosphate isomerase activity between 50 and 60% of normal. The enzyme of the propositus had normal Michaelis-Menten constants both for F-6-P and G-6-P, but abnormal pH optimum and decreased heat stability at 48 degrees C. On starch-gel electrophoresis the father's enzyme was normal but the mother's showed a cathodic migrating band in addition to the normal one. The enzyme from the propositus exhibited only one band with cathodal mobility of 116% of the main band found in normal subjects. It is postulated that the propositus is double heterozygous for two abnormal alleles, and the mother contributes a mutant allele with abnormal electrophoretic mobility and thermolability at 48 degrees C whereas the father contributes an allele without enzymatic activity.", "contents": "Glucose phosphate isomerase deficiency with hereditary hemolytic anemia in a Spanish family: clinical and familial studies. A new case of glucose phosphate isomerase deficiency associated with cogenital nonspherocytic hemolytic anemia is described in a 12-year-old girl of Spanish origin. The parents exhibited erythrocyte glucose phosphate isomerase activity between 50 and 60% of normal. The enzyme of the propositus had normal Michaelis-Menten constants both for F-6-P and G-6-P, but abnormal pH optimum and decreased heat stability at 48 degrees C. On starch-gel electrophoresis the father's enzyme was normal but the mother's showed a cathodic migrating band in addition to the normal one. The enzyme from the propositus exhibited only one band with cathodal mobility of 116% of the main band found in normal subjects. It is postulated that the propositus is double heterozygous for two abnormal alleles, and the mother contributes a mutant allele with abnormal electrophoretic mobility and thermolability at 48 degrees C whereas the father contributes an allele without enzymatic activity."}
{"id": "PMID:240777", "title": "Inability of thymus cells from newborn donors to restore transplantation immunity in athymic mice.", "content": "Passive transfer of thymus cells from congenic donors to athymic mice reconstitutes the recipient's capacity to reject allogeneic skin grafts, provided the donor is immunologically mature and the number of thymus cells from the adult donor is high enough. Passive transfer of thymus cells from adult allogeneic donors induces a mild to severe graft-versus-host disease and the grafts are retained until death. These results are interpreted on the basis of recent findings on the endocrine conditions of congenitally athymic mice and on the previous data on the hormone dependence of thymus cells to acquire immunocompetence. It is proposed that a normal host environment is a prerequisite for the thymus-derived cells to perform in cell-mediated immune reactions.", "contents": "Inability of thymus cells from newborn donors to restore transplantation immunity in athymic mice. Passive transfer of thymus cells from congenic donors to athymic mice reconstitutes the recipient's capacity to reject allogeneic skin grafts, provided the donor is immunologically mature and the number of thymus cells from the adult donor is high enough. Passive transfer of thymus cells from adult allogeneic donors induces a mild to severe graft-versus-host disease and the grafts are retained until death. These results are interpreted on the basis of recent findings on the endocrine conditions of congenitally athymic mice and on the previous data on the hormone dependence of thymus cells to acquire immunocompetence. It is proposed that a normal host environment is a prerequisite for the thymus-derived cells to perform in cell-mediated immune reactions."}
{"id": "PMID:240778", "title": "Variation in internal polysaccharide synthesis among Streptococcus mutans strains.", "content": "Five strains, representative of Streptococcus mutans genetic group III antigenic group d, synthesized and degraded less intracellular polysaccharide (IPS) then 17 strains representative of other S. mutans groups. The strains that synthesize IPS degraded it rapidly. The production of acid  in titratable amounts from endogenous IPS was usually complete within 1 h. IPS synthesis in S. mutans increased abruptly at culture glucose concentrations between 0.2 and 0.5% and was quantitated as both iodine-and glucose oxidase-positive material in cell hyrolysates. IPS degradation was measured by acid production in a pH-stat maintained at 7. The existence within group III d of a strain recently shown to be cariogenic in experimental animals suggest that IPS may not be a prerequisite for virulence in these cariogenic bacteria.", "contents": "Variation in internal polysaccharide synthesis among Streptococcus mutans strains. Five strains, representative of Streptococcus mutans genetic group III antigenic group d, synthesized and degraded less intracellular polysaccharide (IPS) then 17 strains representative of other S. mutans groups. The strains that synthesize IPS degraded it rapidly. The production of acid  in titratable amounts from endogenous IPS was usually complete within 1 h. IPS synthesis in S. mutans increased abruptly at culture glucose concentrations between 0.2 and 0.5% and was quantitated as both iodine-and glucose oxidase-positive material in cell hyrolysates. IPS degradation was measured by acid production in a pH-stat maintained at 7. The existence within group III d of a strain recently shown to be cariogenic in experimental animals suggest that IPS may not be a prerequisite for virulence in these cariogenic bacteria."}
{"id": "PMID:240779", "title": "Characterization of a dextranase produced by an oral strain of Actinomyces israelii.", "content": "A dextranase-producing, gram-positive, anaerobic, rod-shaped bacterium isolated from human dental plaque was identified as Actinomyces israeli. Although the extracellular dextranase (EC 3.2.1.11) formed by this microbe appeared to be constitutively produced, the bacterium did not utilize the reaction products as a carbon source during growth. A striking feature of the dextranase was the formation of two distinct groups of oligosaccharide end products. The two groups presumably correspond to the limit dextran and the released reaction product which appeared to be cleaved from the end(s) of larger dextran molecules. Low levels of dextranase activity were measured by [3H]NaBH4 reduction and alcohol fixation of the large, tritiated end products on filter paper disks. Of the carbohydrate substrates tested, only alpha-1,6-linked glucans were cleaved. The enzyme did not exhibit any metal ion requirements, and its pH optimum was 6.3. It is suggested that the A. israelii dextranase may function as a regulatory factor during extracellular in vivo glucan synthesis from sucrose by various plaque microbes.", "contents": "Characterization of a dextranase produced by an oral strain of Actinomyces israelii. A dextranase-producing, gram-positive, anaerobic, rod-shaped bacterium isolated from human dental plaque was identified as Actinomyces israeli. Although the extracellular dextranase (EC 3.2.1.11) formed by this microbe appeared to be constitutively produced, the bacterium did not utilize the reaction products as a carbon source during growth. A striking feature of the dextranase was the formation of two distinct groups of oligosaccharide end products. The two groups presumably correspond to the limit dextran and the released reaction product which appeared to be cleaved from the end(s) of larger dextran molecules. Low levels of dextranase activity were measured by [3H]NaBH4 reduction and alcohol fixation of the large, tritiated end products on filter paper disks. Of the carbohydrate substrates tested, only alpha-1,6-linked glucans were cleaved. The enzyme did not exhibit any metal ion requirements, and its pH optimum was 6.3. It is suggested that the A. israelii dextranase may function as a regulatory factor during extracellular in vivo glucan synthesis from sucrose by various plaque microbes."}
{"id": "PMID:240776", "title": "Optimal conditions for the fusion of lymphoid cell lines.", "content": "A series of hydrolytic enzymes were compared with lysolecithin, glycerol monooleate, and inactivated Sendai virus for their ability to bring about the fusion of several human and mouse lymphoid cell lines. The agents were tried alone and in various combinations, and a variety of incubation conditions were tested to determine those optimal for fusion. Sendai virus was found to produce the best results with the mouse lymphoid cells; lysolecithin plus glycerol monooleate was slightly superior with the human lymphoid cells. A mixture of hyaluronidase plus collagenase produced low (2 to 6%), but significant, fusion of the human lymphoid cells; both the human and mouse lymphoid cell lines were found to contain relatively high amounts of prolyl hydroxylase, the enzyme which forms collagen from protocollagen. The maximum fusion obtained with the human cells was 16%; with a mouse plasmacytoma line, the maximum was 7.5%; and with a mouse leukemic line derived from L5178Y, the maximum was 60%.", "contents": "Optimal conditions for the fusion of lymphoid cell lines. A series of hydrolytic enzymes were compared with lysolecithin, glycerol monooleate, and inactivated Sendai virus for their ability to bring about the fusion of several human and mouse lymphoid cell lines. The agents were tried alone and in various combinations, and a variety of incubation conditions were tested to determine those optimal for fusion. Sendai virus was found to produce the best results with the mouse lymphoid cells; lysolecithin plus glycerol monooleate was slightly superior with the human lymphoid cells. A mixture of hyaluronidase plus collagenase produced low (2 to 6%), but significant, fusion of the human lymphoid cells; both the human and mouse lymphoid cell lines were found to contain relatively high amounts of prolyl hydroxylase, the enzyme which forms collagen from protocollagen. The maximum fusion obtained with the human cells was 16%; with a mouse plasmacytoma line, the maximum was 7.5%; and with a mouse leukemic line derived from L5178Y, the maximum was 60%."}
{"id": "PMID:240780", "title": "The relative potencies and beta2-selectivities of intravenous rimiterol, salbutamol and isoprenaline in asthmatic patients.", "content": "The bronchodilating efficacy and the degree of beta2-selectivity of rimiterol, salbutamol and isoprenaline were determined in seven asthmatic patients. Rimiterol, 0.5 (high dose) and 0.05 mug/kg/min (low dose), salbutamol, 0.3 and 0.03 mug/kg/min, isoprenaline, 0.05 and 0.005 mug/kg/min, and placebo were administered by a single intravenous injection over 6 minutes in a double-blind trial. Airway resistance, heart rate, blood pressure and skeletal muscle tremor were measured before and at various times for 2 hours after each injection. The high doses of rimiterol (37%), salbutamol (37%) and isoprenaline (32%) produced immediate and effective bronchodilatation. The duration of action of rimiterol and isoprenaline was similar and shorter than that of salbutamol. For these ventilatory responses there were heart rate increases of 32, 20 and 40 beats/min for rimiterol, salbutamol and isoprenaline, respectively. The three drugs produced similar increases in pulse pressure and tremor. Dose-responses were obtained for each drug with all parameters measured and significant differences at various times found. Isoprenaline was approximately 8 and 5 times as potent as rimiterol and salbutamol, respectively, in bronchodilator action, when equimolar doses were compared. Similarly, isoprenaline was approximately 16 and 12 times as potent in increasing the heart rate as rimiterol and salbutamol, respectively. For an equal bronchodilator action, isoprenaline increased the heart rate 2 and 2.5 times more than rimiterol and salbutamol, respectively. Rimiterol is an effective, short-acting bronchodilator, with similar beta2-selectivity to salbutamol, when administered intravenously to asthmatic patients. The relative potencies and degrees of beta2-selectivity of these drugs depend partly on their route of administration.", "contents": "The relative potencies and beta2-selectivities of intravenous rimiterol, salbutamol and isoprenaline in asthmatic patients. The bronchodilating efficacy and the degree of beta2-selectivity of rimiterol, salbutamol and isoprenaline were determined in seven asthmatic patients. Rimiterol, 0.5 (high dose) and 0.05 mug/kg/min (low dose), salbutamol, 0.3 and 0.03 mug/kg/min, isoprenaline, 0.05 and 0.005 mug/kg/min, and placebo were administered by a single intravenous injection over 6 minutes in a double-blind trial. Airway resistance, heart rate, blood pressure and skeletal muscle tremor were measured before and at various times for 2 hours after each injection. The high doses of rimiterol (37%), salbutamol (37%) and isoprenaline (32%) produced immediate and effective bronchodilatation. The duration of action of rimiterol and isoprenaline was similar and shorter than that of salbutamol. For these ventilatory responses there were heart rate increases of 32, 20 and 40 beats/min for rimiterol, salbutamol and isoprenaline, respectively. The three drugs produced similar increases in pulse pressure and tremor. Dose-responses were obtained for each drug with all parameters measured and significant differences at various times found. Isoprenaline was approximately 8 and 5 times as potent as rimiterol and salbutamol, respectively, in bronchodilator action, when equimolar doses were compared. Similarly, isoprenaline was approximately 16 and 12 times as potent in increasing the heart rate as rimiterol and salbutamol, respectively. For an equal bronchodilator action, isoprenaline increased the heart rate 2 and 2.5 times more than rimiterol and salbutamol, respectively. Rimiterol is an effective, short-acting bronchodilator, with similar beta2-selectivity to salbutamol, when administered intravenously to asthmatic patients. The relative potencies and degrees of beta2-selectivity of these drugs depend partly on their route of administration."}
{"id": "PMID:240782", "title": "Inhibition of phenytoin metabolism by other drugs used in epilepsy.", "content": "Phenytoin metabolism is saturable within its normal therapeutic range and, therefore, small changes in the activity of the enzyme can lead to marked changes in serum phenytoin concentrations. The anticonvulsant drugs sulthiame and pheneturide both inhibit the metabolism of phenytoin. The mechanism of this interaction appears to be different for these two drugs. Nortriptyline produces a small increase in serum phenytoin concentrations, but this is unlikely to be of clinical importance. Case reports suggest that both chlorpromazine and chloramphenicol inhibit phenytoin metabolism to a significant degree.", "contents": "Inhibition of phenytoin metabolism by other drugs used in epilepsy. Phenytoin metabolism is saturable within its normal therapeutic range and, therefore, small changes in the activity of the enzyme can lead to marked changes in serum phenytoin concentrations. The anticonvulsant drugs sulthiame and pheneturide both inhibit the metabolism of phenytoin. The mechanism of this interaction appears to be different for these two drugs. Nortriptyline produces a small increase in serum phenytoin concentrations, but this is unlikely to be of clinical importance. Case reports suggest that both chlorpromazine and chloramphenicol inhibit phenytoin metabolism to a significant degree."}
{"id": "PMID:240783", "title": "A comparative study of the activity of beta-adrenoceptor antagonists in man.", "content": "1. In healthy subjects the plasma concentration of unchanged drug, heart rate response to excerise and attenuation of isoprenaline tachycardia were maximal at one hour after ingestion of a range of doses of propranolol, oxprenolol, practolol, tolamolol, atenolol and metoprolol. 2. There was a within-drug relationship between plasma concentration of unchanged drug and the attenuation of exercise and iosprenaline tachycardia. There was no similar between-drug relationship. 3. There was a similar exponential relationship between oral dose and reduction of exercise tachycardia for all six drugs. 4. The linear relationship between oral dose and antagonism of infused isoprenaline was significantly greater for oxprenolol and propranolol than for the other four drugs. 5. \"Cardioselective\" activity was the only ancillary pharmacological property which differentiated the activity of these drugs in normal subjects.", "contents": "A comparative study of the activity of beta-adrenoceptor antagonists in man. 1. In healthy subjects the plasma concentration of unchanged drug, heart rate response to excerise and attenuation of isoprenaline tachycardia were maximal at one hour after ingestion of a range of doses of propranolol, oxprenolol, practolol, tolamolol, atenolol and metoprolol. 2. There was a within-drug relationship between plasma concentration of unchanged drug and the attenuation of exercise and iosprenaline tachycardia. There was no similar between-drug relationship. 3. There was a similar exponential relationship between oral dose and reduction of exercise tachycardia for all six drugs. 4. The linear relationship between oral dose and antagonism of infused isoprenaline was significantly greater for oxprenolol and propranolol than for the other four drugs. 5. \"Cardioselective\" activity was the only ancillary pharmacological property which differentiated the activity of these drugs in normal subjects."}
{"id": "PMID:240784", "title": "Alteration of hemodynamics, blood gases and lung morphology in bromocarbamide intoxication (animal experiments).", "content": "The reaction to animals in bromocarbamide intoxication with respect to blood pressure, resistance in the systemic and pulmonary circulation, cardiac output and arterial blood gas values is presented and discussed in reference to morphological changes in the lung. The animals die due to peripheral  circulatory failure if paralysis of respiration is prevented by means of artificial ventilation. The observed morphological lung changes are not the cause of death.", "contents": "Alteration of hemodynamics, blood gases and lung morphology in bromocarbamide intoxication (animal experiments). The reaction to animals in bromocarbamide intoxication with respect to blood pressure, resistance in the systemic and pulmonary circulation, cardiac output and arterial blood gas values is presented and discussed in reference to morphological changes in the lung. The animals die due to peripheral  circulatory failure if paralysis of respiration is prevented by means of artificial ventilation. The observed morphological lung changes are not the cause of death."}
{"id": "PMID:240785", "title": "Folic acid conjugase from Plasma. I. Partial purification and properties.", "content": "Human plasma conjugase was partially purified by ammonium sulphate and DEAE-cellulose column fractionation. The pH optimum was found to be 4.5. The enzyme followed normal Michaelis-Menten Kinetics. The Km value was found to be 1.4 x 10(-7)M for folylheptaglutatmate assuming this compound to be the predominant form of folate in yeast extract. The enzyme required sulfhydryl compounds for full activity. Differential microbiological assay of the conjugase reaction product using L. casei and S. faecalis as the test organisms revealed that during the initial stage of the reaction considerable portion of the reaction product was at polyglutamyl stage. On prolonged incubation polyglutamates decreased due to further hydrolysis of the gamma-glutamyl residues. The plasma conjugase activity of different species of animals showed wide variations. Goat, dog and rabbit plasma had neglibible activity while monkey, guinea pig and chick plasma had moderate activity. Bovine plasma had low activity while rat plasma had high activity. The plasma conjugase activity of normal Indian adults ranged from 400 to 900 units per ml, and there was no significant sex difference. The values obtained are considerably higher than those reported in literature.", "contents": "Folic acid conjugase from Plasma. I. Partial purification and properties. Human plasma conjugase was partially purified by ammonium sulphate and DEAE-cellulose column fractionation. The pH optimum was found to be 4.5. The enzyme followed normal Michaelis-Menten Kinetics. The Km value was found to be 1.4 x 10(-7)M for folylheptaglutatmate assuming this compound to be the predominant form of folate in yeast extract. The enzyme required sulfhydryl compounds for full activity. Differential microbiological assay of the conjugase reaction product using L. casei and S. faecalis as the test organisms revealed that during the initial stage of the reaction considerable portion of the reaction product was at polyglutamyl stage. On prolonged incubation polyglutamates decreased due to further hydrolysis of the gamma-glutamyl residues. The plasma conjugase activity of different species of animals showed wide variations. Goat, dog and rabbit plasma had neglibible activity while monkey, guinea pig and chick plasma had moderate activity. Bovine plasma had low activity while rat plasma had high activity. The plasma conjugase activity of normal Indian adults ranged from 400 to 900 units per ml, and there was no significant sex difference. The values obtained are considerably higher than those reported in literature."}
{"id": "PMID:240786", "title": "Folic acid conjugase from plasma. II. Studies on the source of the enzyme in blood.", "content": "Following the administration of carbon tetrachloride to rats, the liver conjugase level decreased with 4 hours and continued to be low till 24 hours. Plasma conjugase did not change till 6 hours after administration, but at 24 hours showed a significant increase. Histological examination of the livers revealed liver damage even by 6 hours following carbon tetrachloride administration. However, centrilobular liver cell necrosis could be seen only in the livers of animals killed after 24 hours following carbon tetrachloride administration. The properties of plasma and liver conjugases were similar. The pH optimum of the conjugase in the plasma obtained at 24 hours after carbon tetrachloride administration was 4.5 which is the same as that of the liver conjugase and the Km values were also almost the same. Both the enzymes were stimulated by thiol compounds. The inverse relationship between liver and plasma conjugase activities following carbon tetrachloride administration suggested that liver is probably the source of plasma conjugase.", "contents": "Folic acid conjugase from plasma. II. Studies on the source of the enzyme in blood. Following the administration of carbon tetrachloride to rats, the liver conjugase level decreased with 4 hours and continued to be low till 24 hours. Plasma conjugase did not change till 6 hours after administration, but at 24 hours showed a significant increase. Histological examination of the livers revealed liver damage even by 6 hours following carbon tetrachloride administration. However, centrilobular liver cell necrosis could be seen only in the livers of animals killed after 24 hours following carbon tetrachloride administration. The properties of plasma and liver conjugases were similar. The pH optimum of the conjugase in the plasma obtained at 24 hours after carbon tetrachloride administration was 4.5 which is the same as that of the liver conjugase and the Km values were also almost the same. Both the enzymes were stimulated by thiol compounds. The inverse relationship between liver and plasma conjugase activities following carbon tetrachloride administration suggested that liver is probably the source of plasma conjugase."}
{"id": "PMID:240787", "title": "Gamma-glutamyl transpeptidase as an aid in the diagnosis of liver metastases.", "content": "Serum gamma-glutamyl transpeptidase (GGTP) activity was examined in 79 patients. Of these, 49 had diverse malignant tumors, some of which had metastasized to the liver, and 18 had benign diseases of the liver, gallbladder and bile ducts. Enzyme activity increased significantly in all but two patients in whom liver metastases were found. All but one of the patients with malignant tumors, but without liver metastases, showed normal GGTP activity. GGTP activity was elevated in all cases of jaundice. In the absence of jaundice, elevated GGTP activity is suggestive of the presence of liver metastases.", "contents": "Gamma-glutamyl transpeptidase as an aid in the diagnosis of liver metastases. Serum gamma-glutamyl transpeptidase (GGTP) activity was examined in 79 patients. Of these, 49 had diverse malignant tumors, some of which had metastasized to the liver, and 18 had benign diseases of the liver, gallbladder and bile ducts. Enzyme activity increased significantly in all but two patients in whom liver metastases were found. All but one of the patients with malignant tumors, but without liver metastases, showed normal GGTP activity. GGTP activity was elevated in all cases of jaundice. In the absence of jaundice, elevated GGTP activity is suggestive of the presence of liver metastases."}
{"id": "PMID:240788", "title": "[Physiology of the free-skin transplant].", "content": "The publications on the physiology of the free full thickness skin autograft are reported with special reference to the newer ones as a synopsis of literature. Emphasis is placed upon the interesting findings on plastic surgery and especially upon the operative treatment of alopecia.", "contents": "[Physiology of the free-skin transplant]. The publications on the physiology of the free full thickness skin autograft are reported with special reference to the newer ones as a synopsis of literature. Emphasis is placed upon the interesting findings on plastic surgery and especially upon the operative treatment of alopecia."}
{"id": "PMID:240789", "title": "Antibiograms of pathogenic bacteria isolated from laboratory animals.", "content": "Study of antibiotic sensitivity patterns of 178 bacterial isolants from laboratory animals revealed that these bacteria in general were sensitive to many commonly used antibiotics; however, there were notable exceptions. This report presents current antibiotic sensitivity patterns of most gram-negative and gram-positive bacterial pathogens common to laboratory animals.", "contents": "Antibiograms of pathogenic bacteria isolated from laboratory animals. Study of antibiotic sensitivity patterns of 178 bacterial isolants from laboratory animals revealed that these bacteria in general were sensitive to many commonly used antibiotics; however, there were notable exceptions. This report presents current antibiotic sensitivity patterns of most gram-negative and gram-positive bacterial pathogens common to laboratory animals."}
{"id": "PMID:240790", "title": "Studies on lankacidin-group (T-2636) antibiotics. X. Microbial conversion of lankacidin-group antibiotics.", "content": "Lankacidin C, a component of lankacidin-group (T-2636) antibiotics, was esterified to lankacidin C 8-butyrate in the presence of methyl butyrate by culture broth and by cell-free extract of Bacillus megaterium IFO 12108. In addition, methyl isobutyrate, methyl valerate and methyl isovalerate served as acyl donors for the esterification, and lankacidin C 8-isobutyrate, lankacidin C 8-valerate and lankacidin C 8-isovalerate were formed respectively. Lankacidin C 8, 14-dibutyrate was hydrolyzed to lankacidin C 14-butyrate by the same organism.", "contents": "Studies on lankacidin-group (T-2636) antibiotics. X. Microbial conversion of lankacidin-group antibiotics. Lankacidin C, a component of lankacidin-group (T-2636) antibiotics, was esterified to lankacidin C 8-butyrate in the presence of methyl butyrate by culture broth and by cell-free extract of Bacillus megaterium IFO 12108. In addition, methyl isobutyrate, methyl valerate and methyl isovalerate served as acyl donors for the esterification, and lankacidin C 8-isobutyrate, lankacidin C 8-valerate and lankacidin C 8-isovalerate were formed respectively. Lankacidin C 8, 14-dibutyrate was hydrolyzed to lankacidin C 14-butyrate by the same organism."}
{"id": "PMID:240795", "title": "Nonperipheral chemoreceptor stimulation of ventilation by cyanide.", "content": "To assess the ventilatory responses elicited by changes of tissue hypoxia, sodium cyanide (0.12 mg/kg-min for 10 min) was infused into the upper abdominal aorta of anesthetized dogs. These infusions produced decreases in oxygen consumption, increases in arterial lactate concentration, and increases in arterial lactate/pyruvate ratio. Coincident with these metabolic changes of hypoxia, minute ventilation (VE) increased 228 +/- SE 36% and arterial PCO2 decreased 21 +/- SE 2 mmHg; therefore, pH increased both in arterial blood in and cisternal cerebrospinal fluid. Following infusion of cyanide into the abdominal aorta, small quantities of cyanide (48 +/- SE 14 mumol/liter) appeared in carotid arterial blood. To evaluate the possibility that the observed increases in VE were due to stimulation of peripheral arterial chemoreceptors by the recirculating cyanide, the carotid and aortic chemoreceptors were denervated in four dogs. Nonetheless, after intra-aortic infusion of sodium cyanide (1.2 mg/kg), ventilation in these chemodenervated animals again increased considerably (154 +/- SE 36%). In order to explore the possibility that cyanide infusion can stimulate ventilation by an extracranial mechanism, heads of vagotomized dogs (including the carotid bodies) were perfused entirely by donor dogs. The intra-aortic infusion of sodium cyanide (0.9 mg/kg) into these head-perfused animals still caused large increases in VE (163 +/- SE 19%). It is concluded that intra-aortic cyanide infusions stimulate VE by an extracranial mechanism other than the carotid and aortic chemoreceptors.", "contents": "Nonperipheral chemoreceptor stimulation of ventilation by cyanide. To assess the ventilatory responses elicited by changes of tissue hypoxia, sodium cyanide (0.12 mg/kg-min for 10 min) was infused into the upper abdominal aorta of anesthetized dogs. These infusions produced decreases in oxygen consumption, increases in arterial lactate concentration, and increases in arterial lactate/pyruvate ratio. Coincident with these metabolic changes of hypoxia, minute ventilation (VE) increased 228 +/- SE 36% and arterial PCO2 decreased 21 +/- SE 2 mmHg; therefore, pH increased both in arterial blood in and cisternal cerebrospinal fluid. Following infusion of cyanide into the abdominal aorta, small quantities of cyanide (48 +/- SE 14 mumol/liter) appeared in carotid arterial blood. To evaluate the possibility that the observed increases in VE were due to stimulation of peripheral arterial chemoreceptors by the recirculating cyanide, the carotid and aortic chemoreceptors were denervated in four dogs. Nonetheless, after intra-aortic infusion of sodium cyanide (1.2 mg/kg), ventilation in these chemodenervated animals again increased considerably (154 +/- SE 36%). In order to explore the possibility that cyanide infusion can stimulate ventilation by an extracranial mechanism, heads of vagotomized dogs (including the carotid bodies) were perfused entirely by donor dogs. The intra-aortic infusion of sodium cyanide (0.9 mg/kg) into these head-perfused animals still caused large increases in VE (163 +/- SE 19%). It is concluded that intra-aortic cyanide infusions stimulate VE by an extracranial mechanism other than the carotid and aortic chemoreceptors."}
{"id": "PMID:240796", "title": "Adaptation of brain monoamine synthesis to hypoxia in the rat.", "content": "Oxygen is a substrate in the synthesis of the neurotransmitters, norepinephrine, dopamine, and serotonin. Changes in environmental oxygen appear to cause corresponding alterations in brain monoamine synthesis in vivo. The effect of chronic hypoxia was studied by exposing rats to 10% oxygen for up to 36 h. Brain monoamine synthesis, estimated in vivo, decreased initially and then returned to control levels, despite continued exposure to 10% oxygen. During this apparent adaptation to hypoxia, there were no changes in the concentration of brain serotonin, norepinephrine, dopamine, or tryptophan, while brain tryosine increased after 24 h of exposure. Tyrosine hydroxylase activity in vitro was not altered by the exposure to 10% oxygen. Evidence of hypoxic adaptation in these rats, a rightward shift of their hemoglobin dissociation curves, was found after 24 h of exposure. The adaptation of brain monoamine synthesis to hypoxia appeared to correlate with adaptive changes in brain tissue oxygen rather than any change in the intraneuronal regulation of amine synthesis.", "contents": "Adaptation of brain monoamine synthesis to hypoxia in the rat. Oxygen is a substrate in the synthesis of the neurotransmitters, norepinephrine, dopamine, and serotonin. Changes in environmental oxygen appear to cause corresponding alterations in brain monoamine synthesis in vivo. The effect of chronic hypoxia was studied by exposing rats to 10% oxygen for up to 36 h. Brain monoamine synthesis, estimated in vivo, decreased initially and then returned to control levels, despite continued exposure to 10% oxygen. During this apparent adaptation to hypoxia, there were no changes in the concentration of brain serotonin, norepinephrine, dopamine, or tryptophan, while brain tryosine increased after 24 h of exposure. Tyrosine hydroxylase activity in vitro was not altered by the exposure to 10% oxygen. Evidence of hypoxic adaptation in these rats, a rightward shift of their hemoglobin dissociation curves, was found after 24 h of exposure. The adaptation of brain monoamine synthesis to hypoxia appeared to correlate with adaptive changes in brain tissue oxygen rather than any change in the intraneuronal regulation of amine synthesis."}
{"id": "PMID:240797", "title": "Ventilatory interaction between hypoxia and [H+] at chemoreceptors of man.", "content": "By measuring ventilation during isocapnic progressive hypoxia, peripheral chemoreceptor sensitivity to acute hypoxia (deltaV40) was measured in five normal young men under four sets of conditions: 1) at sea level at the subject's resting PCO2, 2) at sea level with PCO2 5 Torr above resting PCO2, 3) after 24 h at a simulated altitude of 4,267 m (PB = 447 Torr) at the subject's resting PCO2 measured during acute hyperoxia, and 4) after 24 h at high altitude, with PCO2 elevated to the subject's sea-level resting PCO2. With this experimental design, we were able to systematically vary the PCO2 and [H+] at the peripheral and central chemoreceptors of man. When mean pHa was decreased from 7.424 to 7.377 without significant change in PACO2, the mean deltaV40 increased from 18.0 to 55.9 1/min. Conversely, when mean PACO2 was altered between 33.8 and 41.6 Torr with pHa held relatively constant, the mean deltaV40 did not change. This suggests that it is the H+ and not CO2 which interacts with hypoxia in stimulating the ventilation of man. An additional finding was that the intrinsic sensitivity of the peripheral chemoreceptors to acute hypoxia did not change during 24 h of acclimatization to high altitude.", "contents": "Ventilatory interaction between hypoxia and [H+] at chemoreceptors of man. By measuring ventilation during isocapnic progressive hypoxia, peripheral chemoreceptor sensitivity to acute hypoxia (deltaV40) was measured in five normal young men under four sets of conditions: 1) at sea level at the subject's resting PCO2, 2) at sea level with PCO2 5 Torr above resting PCO2, 3) after 24 h at a simulated altitude of 4,267 m (PB = 447 Torr) at the subject's resting PCO2 measured during acute hyperoxia, and 4) after 24 h at high altitude, with PCO2 elevated to the subject's sea-level resting PCO2. With this experimental design, we were able to systematically vary the PCO2 and [H+] at the peripheral and central chemoreceptors of man. When mean pHa was decreased from 7.424 to 7.377 without significant change in PACO2, the mean deltaV40 increased from 18.0 to 55.9 1/min. Conversely, when mean PACO2 was altered between 33.8 and 41.6 Torr with pHa held relatively constant, the mean deltaV40 did not change. This suggests that it is the H+ and not CO2 which interacts with hypoxia in stimulating the ventilation of man. An additional finding was that the intrinsic sensitivity of the peripheral chemoreceptors to acute hypoxia did not change during 24 h of acclimatization to high altitude."}
{"id": "PMID:240798", "title": "Hypothermia and rewarming induced by surface and He-O2 inhalate temperature control.", "content": "Hypothermia and rewarming were induced by a combination of temperature-controlled surface and inhalate methods in rabbits. To facilitate respiratory heat exchange, inhalate-respiratory tract temperature and humidity gradients and thermal conductivity were increased. In addition, the upper respiratory tract was bypassed by an endotracheal tube. To aid in maintaining satisfactory circulatory dynamics, hypercapnia and hypoxia were induced. The combined surface and inhalate method produced a markedly more effective rate of cooling than surface temperature-controlled method alone. Animals survived core temperatures as low as 20.9 degrees C with no complications. The noninvasive simplicity of this method suggests its potential applicability in many clinical situations.", "contents": "Hypothermia and rewarming induced by surface and He-O2 inhalate temperature control. Hypothermia and rewarming were induced by a combination of temperature-controlled surface and inhalate methods in rabbits. To facilitate respiratory heat exchange, inhalate-respiratory tract temperature and humidity gradients and thermal conductivity were increased. In addition, the upper respiratory tract was bypassed by an endotracheal tube. To aid in maintaining satisfactory circulatory dynamics, hypercapnia and hypoxia were induced. The combined surface and inhalate method produced a markedly more effective rate of cooling than surface temperature-controlled method alone. Animals survived core temperatures as low as 20.9 degrees C with no complications. The noninvasive simplicity of this method suggests its potential applicability in many clinical situations."}
{"id": "PMID:240799", "title": "Effect of carotid body resection on ventilatory and acid-base control during exercise.", "content": "To investigate the role of the carotid bodies in exercise hyperpnea and acid-base control, normal and carotid body-resected subjects (CBR) were studied during constant-load and incremental exercise. There was no significant difference in the first-breath ventilatory responses to exercise between the groups; some subjects in each reproducibly exhibited abrupt responses. The subsequent change in Ve toward steady state was slower in the CBR group. The steady-state ventilatory responses were the same in both groups at work rates below the anaerobic threshold (AT). However, above the AT, the hyperpnea was less marked in the CBR group. Ve and acid-base measurements revealed that the CBR group failed to hyperventilate in response to the metabolic acidosis of either constant-load or incremental exercise. We conclude that the carotid bodies 1) are not responsible for the initial exercise hyperpnea, 2) do affect the time course of Ve to its steady state, and 3) are responsible for the respiratory compensation for the metabolic acidosis of exercise.", "contents": "Effect of carotid body resection on ventilatory and acid-base control during exercise. To investigate the role of the carotid bodies in exercise hyperpnea and acid-base control, normal and carotid body-resected subjects (CBR) were studied during constant-load and incremental exercise. There was no significant difference in the first-breath ventilatory responses to exercise between the groups; some subjects in each reproducibly exhibited abrupt responses. The subsequent change in Ve toward steady state was slower in the CBR group. The steady-state ventilatory responses were the same in both groups at work rates below the anaerobic threshold (AT). However, above the AT, the hyperpnea was less marked in the CBR group. Ve and acid-base measurements revealed that the CBR group failed to hyperventilate in response to the metabolic acidosis of either constant-load or incremental exercise. We conclude that the carotid bodies 1) are not responsible for the initial exercise hyperpnea, 2) do affect the time course of Ve to its steady state, and 3) are responsible for the respiratory compensation for the metabolic acidosis of exercise."}
{"id": "PMID:240800", "title": "Gas-blood PCO2 gradients during avian gas exchange.", "content": "The avian respiratory system is a crosscurrent gas exchange system. One of the aspects of this type of gas exchange system is that end-expired PCO2 is greater than arterial PCO2, the highest possible value being equal to mixed venous PCO2. We made steady-state measurements of arterial, mixed venous, and end-expired PCO2 in anesthetized, spontaneously breathing chickens during inhalation of room air or 4-8% CO2. We found end-expired PCO2 to be higher than both arterial and mixed venous PCO2, the sign of the differences being such as to oppose passive diffusion. The observation that end-expired PCO2 was higher than arterial PCO2 can be explained on the basis of crosscurrent gas exchange. However, the observation that end-expired PCO2 exceeded mixed venous PCO2 must be accounted for by some other mechanism. The positive end-expired to mixed venous PCO2 gradients can be explained if it is postulated that the charged membrane mechanism suggested by Gurtner et al. (Respiration Physiol. 7: 173-187, 1969) is present in the avian lung.", "contents": "Gas-blood PCO2 gradients during avian gas exchange. The avian respiratory system is a crosscurrent gas exchange system. One of the aspects of this type of gas exchange system is that end-expired PCO2 is greater than arterial PCO2, the highest possible value being equal to mixed venous PCO2. We made steady-state measurements of arterial, mixed venous, and end-expired PCO2 in anesthetized, spontaneously breathing chickens during inhalation of room air or 4-8% CO2. We found end-expired PCO2 to be higher than both arterial and mixed venous PCO2, the sign of the differences being such as to oppose passive diffusion. The observation that end-expired PCO2 was higher than arterial PCO2 can be explained on the basis of crosscurrent gas exchange. However, the observation that end-expired PCO2 exceeded mixed venous PCO2 must be accounted for by some other mechanism. The positive end-expired to mixed venous PCO2 gradients can be explained if it is postulated that the charged membrane mechanism suggested by Gurtner et al. (Respiration Physiol. 7: 173-187, 1969) is present in the avian lung."}
{"id": "PMID:240801", "title": "Awake baboon's ventilatory response to venous and inhaled CO2 loading.", "content": "Steady-state ventilatory responses to CO2 in trained awake baboons were studied to determine the response to a venous CO2 load. CO2 was loaded either directly into the venous blood through an arteriovenous shunt or by addition to the inhaled air. The two modes of loading were adjusted to produce the same increase in minute volume. Minute volume, tidal volume respiratory frequency, end-tidal PCO2, PaCO2, and pHa were measured. PaCO2 and PETCO2 increased the same amount during the two modes of CO2 loading; thus, the response to changes in arterial PCO2, deltaVE/deltaPaCO2, was the same. I conclude that the ventilatory response to venous CO2 loading occurs only through the change in mean arterial PCO2 and thus it is unlikely that there are any important venous CO2 receptors.", "contents": "Awake baboon's ventilatory response to venous and inhaled CO2 loading. Steady-state ventilatory responses to CO2 in trained awake baboons were studied to determine the response to a venous CO2 load. CO2 was loaded either directly into the venous blood through an arteriovenous shunt or by addition to the inhaled air. The two modes of loading were adjusted to produce the same increase in minute volume. Minute volume, tidal volume respiratory frequency, end-tidal PCO2, PaCO2, and pHa were measured. PaCO2 and PETCO2 increased the same amount during the two modes of CO2 loading; thus, the response to changes in arterial PCO2, deltaVE/deltaPaCO2, was the same. I conclude that the ventilatory response to venous CO2 loading occurs only through the change in mean arterial PCO2 and thus it is unlikely that there are any important venous CO2 receptors."}
{"id": "PMID:240802", "title": "Mucociliary tracheal transport rates in man.", "content": "A new method for measuring mucociliary tracheal transport rates (MTTR's) is described. An aqueous aerosol containing albumin microspheres labeled with 99mTc was inhaled in such a manner that it was deposited in local concentrations in the large airways. These boli of microspheres were transported up the trachea and their MTTR's measured using a gamma camera. MTTR's were measured in 42 healthy nonsmoking adults (32 men and 10 women, mean age 28 yr). The mean MTTR's appeared to be log normally distributed with a geometric mean of 3.6 mm/min and a coefficient of variation of 75%. The MTTR's of men and women were similar. Each individual's short-term coefficient of variation was 25%. Twenty-two repeat studies 1 wk to 15 mo apart showed the variation within individuals was less than between individuals. The parasympatholytic drug, atropine (0.6 mg iv) decreased MTTR's for at least 3 h. Inhalation of the sympathomimetic drug, Th1165a increased MTTR's. Chronic and acute smoking did not appreciably change the MTTR'S.", "contents": "Mucociliary tracheal transport rates in man. A new method for measuring mucociliary tracheal transport rates (MTTR's) is described. An aqueous aerosol containing albumin microspheres labeled with 99mTc was inhaled in such a manner that it was deposited in local concentrations in the large airways. These boli of microspheres were transported up the trachea and their MTTR's measured using a gamma camera. MTTR's were measured in 42 healthy nonsmoking adults (32 men and 10 women, mean age 28 yr). The mean MTTR's appeared to be log normally distributed with a geometric mean of 3.6 mm/min and a coefficient of variation of 75%. The MTTR's of men and women were similar. Each individual's short-term coefficient of variation was 25%. Twenty-two repeat studies 1 wk to 15 mo apart showed the variation within individuals was less than between individuals. The parasympatholytic drug, atropine (0.6 mg iv) decreased MTTR's for at least 3 h. Inhalation of the sympathomimetic drug, Th1165a increased MTTR's. Chronic and acute smoking did not appreciably change the MTTR'S."}
{"id": "PMID:240803", "title": "Site of initial glycosylation of mannoproteins from Saccharomyces cerevisiae.", "content": "The cellular site of initial glycosylation of proteins from Saccharomyces cerevisiae has been studied. Short pulses of [U-14C]mannose label the ribosomal fraction of the yeast. Most of the label was associated with polysomes; monosomes contained only a small amount of radioactivity. All of the radioactivity present in the polysomal fraction was accounted by mannose and smaller amounts of glucose and glucosamine. Puromycin treatment detached more than 50% of the radioactivity from the polysomes; treatment of polysomes at pH 10.0 also caused the release of radioactivity. These results indicate that initial sugar binding occurs while the nascent polypeptide chains are still growing on the ribosomes. When the cells were preincubated with 2-deoxy-D-glucose, incorporation of [U-14C]mannose into the polysomes and the cell wall was inhibited, whereas its incorporation into membrane fractions was unimpaired. It was concluded that 2-deoxy-D-glucose inhibited the synthesis of glycoproteins by interference with the initial glycosylation steps at the ribosomal level.", "contents": "Site of initial glycosylation of mannoproteins from Saccharomyces cerevisiae. The cellular site of initial glycosylation of proteins from Saccharomyces cerevisiae has been studied. Short pulses of [U-14C]mannose label the ribosomal fraction of the yeast. Most of the label was associated with polysomes; monosomes contained only a small amount of radioactivity. All of the radioactivity present in the polysomal fraction was accounted by mannose and smaller amounts of glucose and glucosamine. Puromycin treatment detached more than 50% of the radioactivity from the polysomes; treatment of polysomes at pH 10.0 also caused the release of radioactivity. These results indicate that initial sugar binding occurs while the nascent polypeptide chains are still growing on the ribosomes. When the cells were preincubated with 2-deoxy-D-glucose, incorporation of [U-14C]mannose into the polysomes and the cell wall was inhibited, whereas its incorporation into membrane fractions was unimpaired. It was concluded that 2-deoxy-D-glucose inhibited the synthesis of glycoproteins by interference with the initial glycosylation steps at the ribosomal level."}
{"id": "PMID:240804", "title": "Regulation of the ammonia assimilatory enzymes in Salmonella typhimurium.", "content": "The regulation of glutamate dehydrogenase (EC 1.4.1.4), glutamine synthetase (EC 6.3.1.2), and glutamate synthase (EC 2.6.1.53) was examined for cultures of Salmonella typhimurium grown with various nitrogen and amino acid sources. In contrast to the regulatory pattern observed in Klebsiella aerogenes, the glutamate dehydrogenase levels of S. typhimurium do not decrease when glutamine synthetase is derepressed during growth with limiting ammonia. Thus, it appears that the S. typhimurium glutamine synthetase does not regulate the synthesis of glutamate dehydrogenase as reported for K. aerogenes. The glutamate dehydrogenase activity does increase, however, during growth of a glutamate auxotroph with glutamate as a limiting amino acid source. The regulation of glutamate synthase levels is complex with the enzyme activity decreasing during growth with glutamate as a nitrogen source, and during growth of auxotrophs with either glutamine or glutamate as limiting amino acids.", "contents": "Regulation of the ammonia assimilatory enzymes in Salmonella typhimurium. The regulation of glutamate dehydrogenase (EC 1.4.1.4), glutamine synthetase (EC 6.3.1.2), and glutamate synthase (EC 2.6.1.53) was examined for cultures of Salmonella typhimurium grown with various nitrogen and amino acid sources. In contrast to the regulatory pattern observed in Klebsiella aerogenes, the glutamate dehydrogenase levels of S. typhimurium do not decrease when glutamine synthetase is derepressed during growth with limiting ammonia. Thus, it appears that the S. typhimurium glutamine synthetase does not regulate the synthesis of glutamate dehydrogenase as reported for K. aerogenes. The glutamate dehydrogenase activity does increase, however, during growth of a glutamate auxotroph with glutamate as a limiting amino acid source. The regulation of glutamate synthase levels is complex with the enzyme activity decreasing during growth with glutamate as a nitrogen source, and during growth of auxotrophs with either glutamine or glutamate as limiting amino acids."}
{"id": "PMID:240805", "title": "Maltose metabolism of Pseudomonas fluorescens.", "content": "Pseudomonas fluorescens W uses maltose exclusively by hydrolyzing it to glucose via an inducible alpha-glucosidase (alpha-D-glucoside glucohydrolase, EC 3.2.1.20). No evidence for phosphorolytic cleavage or oxidation to maltobionic acid was found in this organism. The alpha-glucosidase was totally intracellular and was most active at pH of 7.0. Induction occurred when cells were incubated with maltotriose or maltose. Induction was rapid and easily detectable within the first 5 min after the addition of the inducer. Glucose and its derivatives did not repress induction. Cells growing on DL-alanine or succinate plus maltose exhibited lower levels of alpha-glucosidase than those grown on maltose alone or maltose plus glucose. Induction required both messenger ribonucleic acid and protein synthesis.", "contents": "Maltose metabolism of Pseudomonas fluorescens. Pseudomonas fluorescens W uses maltose exclusively by hydrolyzing it to glucose via an inducible alpha-glucosidase (alpha-D-glucoside glucohydrolase, EC 3.2.1.20). No evidence for phosphorolytic cleavage or oxidation to maltobionic acid was found in this organism. The alpha-glucosidase was totally intracellular and was most active at pH of 7.0. Induction occurred when cells were incubated with maltotriose or maltose. Induction was rapid and easily detectable within the first 5 min after the addition of the inducer. Glucose and its derivatives did not repress induction. Cells growing on DL-alanine or succinate plus maltose exhibited lower levels of alpha-glucosidase than those grown on maltose alone or maltose plus glucose. Induction required both messenger ribonucleic acid and protein synthesis."}
{"id": "PMID:240806", "title": "Inhibition of amino acid transport by ammonium ion in Saccharomyces cerevisiae.", "content": "The rate of transport of L-amino acids by Saccharomyces cerevisiae epsilon 1278b increased with time in response to nitrogen starvation. This increase could be prevented by the addition of ammonium sulfate or cycloheximide. A slow time-dependent loss of transport activity was observed when ammonium sulfate (or ammonium sulfate plus cycloheximide) was added to cells after 3 h of nitrogen starvation. This loss of activity was not observed in the presence of cycloheximide alone. In a mutant yeast strain which lacks the nicotinamide adenine dinucleotide phosphate-dependent (anabolic) glutamate dehydrogenase, no significant decrease in amino acid transport was observed when ammonium sulfate was added to nitrogen-starved cells. A double mutant, which lacks the nicotinamide adenine dinucleotide phosphate-dependent enzyme and in addition has a depressed level of the nicotinamide adenine dinucleotide-dependent (catabolic) glutamate dehydrogenase, shows the same sensitivity to ammonium ion as the wild-type strain. These data suggest that the inhibition of amino acid transport by ammonium ion results from the uptake of this metabolite into the cell and its subsequent incorporation into the alpha-amino groups of glutamate and other amino acids.", "contents": "Inhibition of amino acid transport by ammonium ion in Saccharomyces cerevisiae. The rate of transport of L-amino acids by Saccharomyces cerevisiae epsilon 1278b increased with time in response to nitrogen starvation. This increase could be prevented by the addition of ammonium sulfate or cycloheximide. A slow time-dependent loss of transport activity was observed when ammonium sulfate (or ammonium sulfate plus cycloheximide) was added to cells after 3 h of nitrogen starvation. This loss of activity was not observed in the presence of cycloheximide alone. In a mutant yeast strain which lacks the nicotinamide adenine dinucleotide phosphate-dependent (anabolic) glutamate dehydrogenase, no significant decrease in amino acid transport was observed when ammonium sulfate was added to nitrogen-starved cells. A double mutant, which lacks the nicotinamide adenine dinucleotide phosphate-dependent enzyme and in addition has a depressed level of the nicotinamide adenine dinucleotide-dependent (catabolic) glutamate dehydrogenase, shows the same sensitivity to ammonium ion as the wild-type strain. These data suggest that the inhibition of amino acid transport by ammonium ion results from the uptake of this metabolite into the cell and its subsequent incorporation into the alpha-amino groups of glutamate and other amino acids."}
{"id": "PMID:240807", "title": "Soluble macromolecular complexes involving bacterial teichoic acids.", "content": "Cell wall and membrane teichoic acids from several bacteria formed soluble complexes with polysaccharides and bovine plasma in alkyl alcohol solutions. Polysaccharides which contain different monomeric units and anomeric configurations complexed with the teichoic acids, suggesting that the interaction is relatively nonspecific. Teichoic acids complexed glycogen or bovine plasma albumin in 50 to 97% ethanol solutions. The macromolecular association between teichoic acids and polysaccharides or proteins was independent of teichoic acid size over a threefold molecular weight range. Glycerol phosphates or an acid hydrolysate of teichoic acid would not complex to either glycogen or bovine plasma albumin in ethanol. The optimal interaction between glycogen and the Bacillus subtilis lipoteichoic acid occurred between pH 4.5 and 8.2. The ability of teichoic acids to bind polysaccharides and proteins in moderate dielectric constant solvents suggests that these polymers may serve as complexing agents for hydrophilic molecules found in membranes.", "contents": "Soluble macromolecular complexes involving bacterial teichoic acids. Cell wall and membrane teichoic acids from several bacteria formed soluble complexes with polysaccharides and bovine plasma in alkyl alcohol solutions. Polysaccharides which contain different monomeric units and anomeric configurations complexed with the teichoic acids, suggesting that the interaction is relatively nonspecific. Teichoic acids complexed glycogen or bovine plasma albumin in 50 to 97% ethanol solutions. The macromolecular association between teichoic acids and polysaccharides or proteins was independent of teichoic acid size over a threefold molecular weight range. Glycerol phosphates or an acid hydrolysate of teichoic acid would not complex to either glycogen or bovine plasma albumin in ethanol. The optimal interaction between glycogen and the Bacillus subtilis lipoteichoic acid occurred between pH 4.5 and 8.2. The ability of teichoic acids to bind polysaccharides and proteins in moderate dielectric constant solvents suggests that these polymers may serve as complexing agents for hydrophilic molecules found in membranes."}
{"id": "PMID:240808", "title": "Aminopeptidases of Bacillus subtilis.", "content": "Three enzymes with L- and one enzyme with D-aminopeptidase (EC 3.4.11; alpha-aminoacyl peptide hydrolase) activity have been separated from each other and partially purified from Bacillus subtilis 168 W.T., distinguished with respect to their molecular weights and catalytic properties, and studied in relation to the physiology of this bacterium. One L-aminopeptidase, designated aminopeptidase I, has a molecular weight of 210,000 +/- 20,000, is produced early in growth, and hydrolyzes L-alanyl-beta-naphthylamide most rapidly. Another, designated aminopeptidase II, molecular weight 67,000 +/- 10,000, is also produced early in growth and hydrolyzes L-lysyl-beta-naphthylamide most rapidly. A third, aminopeptidase III, molecular weight 228,000 +/- 20,000, is produced predominantly in early stationary phase and most efficiently utilizes L-alpha-aspartyl-beta-naphthylamide as substrate. The synthesis of aminopeptidase III in early stationary phase suggests that selective catabolism of peptides occurs at this time, perhaps related to the cessation of growth or the onset of early sporulation-associated events. A D-aminopeptidase which hydrolyzes the carboxyl-blocked dipeptide D-alanyl-D-alanyl-beta-naphthylamide (as well as D-alanyl-beta-naphthylamide and D-alanyl-D-alanyl-D-alanine) has also been identified, separated from aminopeptidase II, and purified 170-fold. D-Aminopeptidase, molecular weight 220,000 +/- 20,000, is localized predominantly in the cell wall and periplasm of the organism. This evidence and the variation of the activity during the growth cycle suggest an important function in cell wall or peptide antibiotic metabolism.", "contents": "Aminopeptidases of Bacillus subtilis. Three enzymes with L- and one enzyme with D-aminopeptidase (EC 3.4.11; alpha-aminoacyl peptide hydrolase) activity have been separated from each other and partially purified from Bacillus subtilis 168 W.T., distinguished with respect to their molecular weights and catalytic properties, and studied in relation to the physiology of this bacterium. One L-aminopeptidase, designated aminopeptidase I, has a molecular weight of 210,000 +/- 20,000, is produced early in growth, and hydrolyzes L-alanyl-beta-naphthylamide most rapidly. Another, designated aminopeptidase II, molecular weight 67,000 +/- 10,000, is also produced early in growth and hydrolyzes L-lysyl-beta-naphthylamide most rapidly. A third, aminopeptidase III, molecular weight 228,000 +/- 20,000, is produced predominantly in early stationary phase and most efficiently utilizes L-alpha-aspartyl-beta-naphthylamide as substrate. The synthesis of aminopeptidase III in early stationary phase suggests that selective catabolism of peptides occurs at this time, perhaps related to the cessation of growth or the onset of early sporulation-associated events. A D-aminopeptidase which hydrolyzes the carboxyl-blocked dipeptide D-alanyl-D-alanyl-beta-naphthylamide (as well as D-alanyl-beta-naphthylamide and D-alanyl-D-alanyl-D-alanine) has also been identified, separated from aminopeptidase II, and purified 170-fold. D-Aminopeptidase, molecular weight 220,000 +/- 20,000, is localized predominantly in the cell wall and periplasm of the organism. This evidence and the variation of the activity during the growth cycle suggest an important function in cell wall or peptide antibiotic metabolism."}
{"id": "PMID:240809", "title": "Membrane-mediated killing of Saccharomyces cerevisiae by glycoproteins from Torulopsis glabrata.", "content": "Cell-free supernatants from cultures of Torulopsis glabrata contained glycoprotein toxins that killed sensitive and killer strains of Saccharomyces cerevisiae with single-hit kinetics. Growing S. cerevisiae treated with the toxins showed a leakage of cellular potassium, partial dissipation of the adenosine triphosphate pool, and a coordinate shutdown of macromolecular synthesis. These pool efflux-stimulating toxins have been partially purified and at least three toxic glycoproteins have been separated. Pool efflux-stimulating toxin activity was stable from pH 3 through 7, though killing was maximal close to pH 4.", "contents": "Membrane-mediated killing of Saccharomyces cerevisiae by glycoproteins from Torulopsis glabrata. Cell-free supernatants from cultures of Torulopsis glabrata contained glycoprotein toxins that killed sensitive and killer strains of Saccharomyces cerevisiae with single-hit kinetics. Growing S. cerevisiae treated with the toxins showed a leakage of cellular potassium, partial dissipation of the adenosine triphosphate pool, and a coordinate shutdown of macromolecular synthesis. These pool efflux-stimulating toxins have been partially purified and at least three toxic glycoproteins have been separated. Pool efflux-stimulating toxin activity was stable from pH 3 through 7, though killing was maximal close to pH 4."}
{"id": "PMID:240810", "title": "Glucose-6-phosphate-dependent pyruvate kinase in Streptococcus mutans.", "content": "Pyruvate kinase of Streptococcus mutans JC 2 had an absolute and specific requirement for glucose-6-phosphate. Inorganic phosphate was a strong inhibitor. The enzyme required K+ or NH4+ and Mg2+ or Mn2+. S. mutans FIL and E 49, Streptococcus bovis ATCC 9809, and Streptococcus salivarius ATCC 13419 had also glucose-6-phosphate-dependent pyruvate kinases, whereas Streptococcus sanguis NCTC 10904 had an enzyme activated by fructose-1,6-diphosphate.", "contents": "Glucose-6-phosphate-dependent pyruvate kinase in Streptococcus mutans. Pyruvate kinase of Streptococcus mutans JC 2 had an absolute and specific requirement for glucose-6-phosphate. Inorganic phosphate was a strong inhibitor. The enzyme required K+ or NH4+ and Mg2+ or Mn2+. S. mutans FIL and E 49, Streptococcus bovis ATCC 9809, and Streptococcus salivarius ATCC 13419 had also glucose-6-phosphate-dependent pyruvate kinases, whereas Streptococcus sanguis NCTC 10904 had an enzyme activated by fructose-1,6-diphosphate."}
{"id": "PMID:240811", "title": "Properties of the nicotinamide adenine dinucleotide phosphate-specific isocitrate dehydrogenase from Blastocladiella emersonii.", "content": "The nicotinamide adenine dinucleotide phosphate (NADP)-specific isocitrate dehydrogenase from Blastocladiella emersonii was purified. The enzyme was very unstable. Satisfactory stability was obtained in the presence of 0.2% ovalbumin. The enzyme had a molecular weight of about 100,000. It did not exhibit homotropic cooperativity for any of it substrates and was not affected by the allosteric modifiers citrate and adenosine monophosphate, diphosphate, and tri-phosphate. The substrate saturation studies showed both intercept and slope effects in Lineweaver-Burk plots. The Km values for isocitrate and NADP were found to be 20 and 10 muM, respectively. The product inhibition pattern was compatible with a random sequential reaction mechanism. The enzyme catalyzed the oxidative decarboxylation of isocitrate about six times better than the reductive carboxylation of alpha-ketoglutarate. The enzyme was inhibited by glyoxylate plus oxalacetate. Assays conducted in the presence of low Mg2+ concentrations exhibited a lag. This lag could be abolished by the addition of reduced NADP to the assay mixture.", "contents": "Properties of the nicotinamide adenine dinucleotide phosphate-specific isocitrate dehydrogenase from Blastocladiella emersonii. The nicotinamide adenine dinucleotide phosphate (NADP)-specific isocitrate dehydrogenase from Blastocladiella emersonii was purified. The enzyme was very unstable. Satisfactory stability was obtained in the presence of 0.2% ovalbumin. The enzyme had a molecular weight of about 100,000. It did not exhibit homotropic cooperativity for any of it substrates and was not affected by the allosteric modifiers citrate and adenosine monophosphate, diphosphate, and tri-phosphate. The substrate saturation studies showed both intercept and slope effects in Lineweaver-Burk plots. The Km values for isocitrate and NADP were found to be 20 and 10 muM, respectively. The product inhibition pattern was compatible with a random sequential reaction mechanism. The enzyme catalyzed the oxidative decarboxylation of isocitrate about six times better than the reductive carboxylation of alpha-ketoglutarate. The enzyme was inhibited by glyoxylate plus oxalacetate. Assays conducted in the presence of low Mg2+ concentrations exhibited a lag. This lag could be abolished by the addition of reduced NADP to the assay mixture."}
{"id": "PMID:240812", "title": "Conversion of Escherichia coli cell-produced metabolic energy into electric form.", "content": "The formation of membrane potential in energized E. coli cells has been investigated by means of ionic penetrants. The fluxes of anions and cations in opposite directions have been observed: anions moved out and cations moved into the cells. The energy-linked uptake of cations was stoichiometrically coupled with the outflow of H+ ions from the cells. The value of a membrane potential in the energized cells calculated from a distribution of permanent cations was in the range of -140 mV (inside minus). The uptake of penetrating cations by deenergized cells has been observed following the non-enzymatic generation of a membrane potential. The influx of synthetic and natural (lactose) penetrants collapsed the non-enzymatic membrane potential. The effect of lactose was sensitive to N-ethyl maleimide. These results are in favour of the conception that in the energized E. coli cells an energy-linked H+-pump generates a membrane potential which is a driving force for the transport of synthetic and some natural penetrants.", "contents": "Conversion of Escherichia coli cell-produced metabolic energy into electric form. The formation of membrane potential in energized E. coli cells has been investigated by means of ionic penetrants. The fluxes of anions and cations in opposite directions have been observed: anions moved out and cations moved into the cells. The energy-linked uptake of cations was stoichiometrically coupled with the outflow of H+ ions from the cells. The value of a membrane potential in the energized cells calculated from a distribution of permanent cations was in the range of -140 mV (inside minus). The uptake of penetrating cations by deenergized cells has been observed following the non-enzymatic generation of a membrane potential. The influx of synthetic and natural (lactose) penetrants collapsed the non-enzymatic membrane potential. The effect of lactose was sensitive to N-ethyl maleimide. These results are in favour of the conception that in the energized E. coli cells an energy-linked H+-pump generates a membrane potential which is a driving force for the transport of synthetic and some natural penetrants."}
{"id": "PMID:240813", "title": "Change of mitochondrial buffering capacity induced by propranolol.", "content": "Propranolol is able to increase the amount of the titratable groups of mitochondrial membranes. This effect occurs with sonicated particles and with liposomes, too. The phenomenon is only seen in the presence of salt solutions, not in sucrose. Propranolol increases the fluorescence of anilino-naphthalene sulphonate (ANS) in mitochondrial suspensions. The increase is counteracted by increasing concentrations of potassium chloride. It is suggested that the increase of the titratable groups results from a decrease of the aggregation of the phospholipids of the membranes. At the same time the environment of the bound ANS molecules is more hydrophobic in sucrose than in potassium chloride. The amount of the buffering groups and the hydrophilicity are in direct and the amount of the buffering groups and the fluorescence of ANS in inverse correlation.", "contents": "Change of mitochondrial buffering capacity induced by propranolol. Propranolol is able to increase the amount of the titratable groups of mitochondrial membranes. This effect occurs with sonicated particles and with liposomes, too. The phenomenon is only seen in the presence of salt solutions, not in sucrose. Propranolol increases the fluorescence of anilino-naphthalene sulphonate (ANS) in mitochondrial suspensions. The increase is counteracted by increasing concentrations of potassium chloride. It is suggested that the increase of the titratable groups results from a decrease of the aggregation of the phospholipids of the membranes. At the same time the environment of the bound ANS molecules is more hydrophobic in sucrose than in potassium chloride. The amount of the buffering groups and the hydrophilicity are in direct and the amount of the buffering groups and the fluorescence of ANS in inverse correlation."}
{"id": "PMID:240814", "title": "Human liver alpha-L-fucosidase. Purification, characterization, and immunochemical studies.", "content": "Human liver alpha-L-fucosidase has been purified 6300-fold to apparent homogeneity with 66% yield by a two-step affinity chromatographic procedure utilizing agarose epsilon-aminocaproyl-fucosamine. Isoelectric focusing revealed that all six isoelectric forms of the enzyme were purified. Polyacrylamide gel electrophoresis of the purified alpha-L-fucosidase demonstrated the presence of six bands of protein which all contained fucosidase activity. The purified enzyme preparation was found to contain only trace amounts of seven glycosidases. Quantitative amino acid analysis was performed on the purified fucosidase. Preliminary carbohydrate analysis indicated that only about 1% of the molecule is carbohydrate. Gel filtration on Sepharose 4B indicated an approximate molecular weight for alpha-L-fucosidase of 175,000 +/- 18,000. High speed sedimentation equilibrium yielded a molecular weight of 230,000 +/- 10,000. Sodium dodecyl sulfate polyacrylamide gels indicated the presence of a single subunit of molecular weight, 50,100 +/- 2,500. The enzyme had a pH optimum of 4.6 with a suggested second optimum of 6.5. Apparent Michaelis constants and maximal velocities were determined on the purified enzyme with respect to the 4-methylumbelliferyl and the p-nitrophenyl substrates and were found to be 0.22 mM and 14.1 mumol/mg of protein/min and 0.43 mM and 19.6 mumol/mg of protein/min, respectively. Several salts had little or no effect on fucosidase activity although Ag+ and Hg2+ completely inactivated the enzyme. Antibodies made against the purified fucosidase were dound to be monospecific against crude human liver supernatant fluids and the pure antigen. No cross-reacting material was detected in the crude liver supernatant fluid from a patient who died with fucosidosis.", "contents": "Human liver alpha-L-fucosidase. Purification, characterization, and immunochemical studies. Human liver alpha-L-fucosidase has been purified 6300-fold to apparent homogeneity with 66% yield by a two-step affinity chromatographic procedure utilizing agarose epsilon-aminocaproyl-fucosamine. Isoelectric focusing revealed that all six isoelectric forms of the enzyme were purified. Polyacrylamide gel electrophoresis of the purified alpha-L-fucosidase demonstrated the presence of six bands of protein which all contained fucosidase activity. The purified enzyme preparation was found to contain only trace amounts of seven glycosidases. Quantitative amino acid analysis was performed on the purified fucosidase. Preliminary carbohydrate analysis indicated that only about 1% of the molecule is carbohydrate. Gel filtration on Sepharose 4B indicated an approximate molecular weight for alpha-L-fucosidase of 175,000 +/- 18,000. High speed sedimentation equilibrium yielded a molecular weight of 230,000 +/- 10,000. Sodium dodecyl sulfate polyacrylamide gels indicated the presence of a single subunit of molecular weight, 50,100 +/- 2,500. The enzyme had a pH optimum of 4.6 with a suggested second optimum of 6.5. Apparent Michaelis constants and maximal velocities were determined on the purified enzyme with respect to the 4-methylumbelliferyl and the p-nitrophenyl substrates and were found to be 0.22 mM and 14.1 mumol/mg of protein/min and 0.43 mM and 19.6 mumol/mg of protein/min, respectively. Several salts had little or no effect on fucosidase activity although Ag+ and Hg2+ completely inactivated the enzyme. Antibodies made against the purified fucosidase were dound to be monospecific against crude human liver supernatant fluids and the pure antigen. No cross-reacting material was detected in the crude liver supernatant fluid from a patient who died with fucosidosis."}
{"id": "PMID:240815", "title": "Mechanism of the reductive activation of succinate dehydrogenase.", "content": "When succinate dehydrogenase contains oxalacetate in firmly bound form, activity cannof the enzyme results in dissociation of oxalacetate and activation of the enzyme. The course of reductive titrations appears the same whether or not the enzyme contains oxalacetate, and complete reduction as monitored by bleaching of chromophoric groups requires the incorporation of 6 to 7 reducing equivalents in either case. The stoichiometry is that expected from the non-heme iron and flavin content of the enzyme. Activation of the enzyme during reductive titrations occurs predominantly with the incorporation of the second pair of electrons, while determination of activation levels at various poised potentials shows that the group involved is reduced with the uptake of 2 H+ and 2 e-. These characteristics are consistent with titration of the flavin moiety rather than non-heme iron groups. Thus it appears that activation is concurrent with the reduction of flavin to the hydroquinone form. From the measured half-reduction potential for activation, that of the flavin in an oxalacetate-free enzyme has been estimated at -90 to -60 mv at pH 7.", "contents": "Mechanism of the reductive activation of succinate dehydrogenase. When succinate dehydrogenase contains oxalacetate in firmly bound form, activity cannof the enzyme results in dissociation of oxalacetate and activation of the enzyme. The course of reductive titrations appears the same whether or not the enzyme contains oxalacetate, and complete reduction as monitored by bleaching of chromophoric groups requires the incorporation of 6 to 7 reducing equivalents in either case. The stoichiometry is that expected from the non-heme iron and flavin content of the enzyme. Activation of the enzyme during reductive titrations occurs predominantly with the incorporation of the second pair of electrons, while determination of activation levels at various poised potentials shows that the group involved is reduced with the uptake of 2 H+ and 2 e-. These characteristics are consistent with titration of the flavin moiety rather than non-heme iron groups. Thus it appears that activation is concurrent with the reduction of flavin to the hydroquinone form. From the measured half-reduction potential for activation, that of the flavin in an oxalacetate-free enzyme has been estimated at -90 to -60 mv at pH 7."}
{"id": "PMID:240816", "title": "Mutants of Escherichia coli defective in membrane phospholipid synthesis. Properties of wild type and Km defective sn-glycerol-3-phosphate acyltransferase activities.", "content": "The sn-glycerol-3-phosphate (glycerol-P) acyltransferase, the first enzyme of membrane phospholipid synthesis in Escherichia coli, was investigated in a wild type and a mutant strain defective in this activity. The mutant strain, selected as a glycerol-P auxotroph, was previously shown to contain a glycerol-P acyltransferase activity with an apparent Km for glycerol-P 10 times higher than that of its parent or revertants. The membranous mutant glycerol-P acyltransferase but did not appear to be thermolabile in vivo. Revertants no longer requiring glycerol-P for growth, showed glycerol-P acyltransferase activity with thermolability properties similar to the wild type. The second phospholipid biosynthetic enzyme, 1-acylglycerol-P acyltransferase, was not thermolabile in membranes containing a thermolabile glycerol-P acyltransferase activity. The pH optimum for the mutant acyltransferase was over 1 pH unit higher than that of the parental activity. Further, the mutant and wild type glycerol-P acyltransferase differed in their response to magnesium chloride and potassium chloride. The palmitoyl-CoA dependence of the wild type and mutant glycerol-P acyltransferase activities were different. The mutant glycerol-P acyltransferase activity was inhibited greater than 90% by Triton X-100 under conditions where the wild type activity was not affected. These experiments provide novel information about the wild type glycerol-P acyltransferase activity of E. coli and provide six additional lines of evidence for the mutant character of the glycerol-P acyltransferase in the mutant strains.", "contents": "Mutants of Escherichia coli defective in membrane phospholipid synthesis. Properties of wild type and Km defective sn-glycerol-3-phosphate acyltransferase activities. The sn-glycerol-3-phosphate (glycerol-P) acyltransferase, the first enzyme of membrane phospholipid synthesis in Escherichia coli, was investigated in a wild type and a mutant strain defective in this activity. The mutant strain, selected as a glycerol-P auxotroph, was previously shown to contain a glycerol-P acyltransferase activity with an apparent Km for glycerol-P 10 times higher than that of its parent or revertants. The membranous mutant glycerol-P acyltransferase but did not appear to be thermolabile in vivo. Revertants no longer requiring glycerol-P for growth, showed glycerol-P acyltransferase activity with thermolability properties similar to the wild type. The second phospholipid biosynthetic enzyme, 1-acylglycerol-P acyltransferase, was not thermolabile in membranes containing a thermolabile glycerol-P acyltransferase activity. The pH optimum for the mutant acyltransferase was over 1 pH unit higher than that of the parental activity. Further, the mutant and wild type glycerol-P acyltransferase differed in their response to magnesium chloride and potassium chloride. The palmitoyl-CoA dependence of the wild type and mutant glycerol-P acyltransferase activities were different. The mutant glycerol-P acyltransferase activity was inhibited greater than 90% by Triton X-100 under conditions where the wild type activity was not affected. These experiments provide novel information about the wild type glycerol-P acyltransferase activity of E. coli and provide six additional lines of evidence for the mutant character of the glycerol-P acyltransferase in the mutant strains."}
{"id": "PMID:240817", "title": "Mutants of Escherichia coli defective in membrane phospholipid synthesis. Phenotypic suppression of sn-glycerol-3-phosphate acyltransferase Km mutants by loss of feedback inhibition of the biosynthetic sn-glycerol-3-phosphate dehydrogenase.", "content": "Revertants of Escherichia coli mutants defective in the first enzyme of membrane phospholipid synthesis, sn-glycerol-3-phosphate (glycerol-P) acyltransferase, were investigated. These glycerol-P acyltransferase mutants, selected as glycerol-P auxotrophs, contained membranous glycerol-P acyltransferase activity with an apparent Km for glycerol-P 10 times higher than the parental activity. The glycerol-P acyltransferase activity was also more thermolabile in vitro than the parental activity. Most revertants no longer requiring glycerol-P for growth regained glycerol-P acyltransferase activity of normal thermolability and apparent Km for glycerol-P. However, two novel revertants were isolated which retained an abnormal glycerol-P acyltransferase activity. The glycerol-P dehydrogenase activities of these novel revertants were about 20-fold less sensitive to feedback inhibition by glycerol-P. The feedback-resistant glycerol-P dehydrogenase co-transduced with gpsA, the structural gene for the glycerol-P dehydrogenase. Further transduction experiments demonstrated that the feedback resistant glycerol-P dehydrogenase phenotypically suppressed the glycerol-P acyltransferase Km lesion. The existence of the class of glycerol-P auxotrophs which owe their phenotype to the glycerol-P acyltransferase Km lesion therefore depends on the feedback regulation of glycerol-P synthesis in E. coli.", "contents": "Mutants of Escherichia coli defective in membrane phospholipid synthesis. Phenotypic suppression of sn-glycerol-3-phosphate acyltransferase Km mutants by loss of feedback inhibition of the biosynthetic sn-glycerol-3-phosphate dehydrogenase. Revertants of Escherichia coli mutants defective in the first enzyme of membrane phospholipid synthesis, sn-glycerol-3-phosphate (glycerol-P) acyltransferase, were investigated. These glycerol-P acyltransferase mutants, selected as glycerol-P auxotrophs, contained membranous glycerol-P acyltransferase activity with an apparent Km for glycerol-P 10 times higher than the parental activity. The glycerol-P acyltransferase activity was also more thermolabile in vitro than the parental activity. Most revertants no longer requiring glycerol-P for growth regained glycerol-P acyltransferase activity of normal thermolability and apparent Km for glycerol-P. However, two novel revertants were isolated which retained an abnormal glycerol-P acyltransferase activity. The glycerol-P dehydrogenase activities of these novel revertants were about 20-fold less sensitive to feedback inhibition by glycerol-P. The feedback-resistant glycerol-P dehydrogenase co-transduced with gpsA, the structural gene for the glycerol-P dehydrogenase. Further transduction experiments demonstrated that the feedback resistant glycerol-P dehydrogenase phenotypically suppressed the glycerol-P acyltransferase Km lesion. The existence of the class of glycerol-P auxotrophs which owe their phenotype to the glycerol-P acyltransferase Km lesion therefore depends on the feedback regulation of glycerol-P synthesis in E. coli."}
{"id": "PMID:240818", "title": "Stoichiometry of 4-methyl sterol oxidase of rat liver microsomes.", "content": "The stoichiometry of 4-methyl sterol oxidase has been investigated by concurrent assays of rates of oxygen consumption, oxidation of reduced pyridine nucleotide, and formation of steroid 4alpha-oic acid, which is the oxidized product of attack of 4-methyl sterol precursors of cholesterol. The basal, steroid-independent rates of oxidation of alpha-NADH and alpha-NADH-dependent oxygen consumption by rat liver microsomes are about 10 to 15% of the rates observed with beta-NADH. Thus, alpha-NADH is substituted for beta-NADH; alpha-NADH oxidation is observed spectrophotometrically. The slow rate of oxygen consumption is measured accurately with a galvanic oxygen electrode that is attached to an offset amplifier. For maximal velocity, 4alpha-hydroxymethyl-5alpha-cholest-7-en-3beta-ol is the steroid substrate, and oxidase activity is induced 2-fold with a dietary bile acid sequestrant. Under these conditions, accurate measurements are obtained for substrate-dependent increments, which are equal to or greater than basal, substrate-independent rates. For each equivalent of hydroxymethyl group oxidized to carboxylic acid, 2 eq each of oxygen and alpha-NADH are consumed. Thus, the stoichiometry is consistent with that expected for two sequential attacks of the 4alpha-hydroxymethyl group by an external mixed function oxidase. In addition to establishing the stoichiometry of the 4-methyl sterol oxidase, the results further demonstrate that the steroidal 4alpha-carboxylic acid is formed from the hydroxymethyl intermediate by catalysis of a mixed function oxidase rather than dehydrogenases.", "contents": "Stoichiometry of 4-methyl sterol oxidase of rat liver microsomes. The stoichiometry of 4-methyl sterol oxidase has been investigated by concurrent assays of rates of oxygen consumption, oxidation of reduced pyridine nucleotide, and formation of steroid 4alpha-oic acid, which is the oxidized product of attack of 4-methyl sterol precursors of cholesterol. The basal, steroid-independent rates of oxidation of alpha-NADH and alpha-NADH-dependent oxygen consumption by rat liver microsomes are about 10 to 15% of the rates observed with beta-NADH. Thus, alpha-NADH is substituted for beta-NADH; alpha-NADH oxidation is observed spectrophotometrically. The slow rate of oxygen consumption is measured accurately with a galvanic oxygen electrode that is attached to an offset amplifier. For maximal velocity, 4alpha-hydroxymethyl-5alpha-cholest-7-en-3beta-ol is the steroid substrate, and oxidase activity is induced 2-fold with a dietary bile acid sequestrant. Under these conditions, accurate measurements are obtained for substrate-dependent increments, which are equal to or greater than basal, substrate-independent rates. For each equivalent of hydroxymethyl group oxidized to carboxylic acid, 2 eq each of oxygen and alpha-NADH are consumed. Thus, the stoichiometry is consistent with that expected for two sequential attacks of the 4alpha-hydroxymethyl group by an external mixed function oxidase. In addition to establishing the stoichiometry of the 4-methyl sterol oxidase, the results further demonstrate that the steroidal 4alpha-carboxylic acid is formed from the hydroxymethyl intermediate by catalysis of a mixed function oxidase rather than dehydrogenases."}
{"id": "PMID:240819", "title": "Diminished 5alpha-reductase activity in extracts of fibroblasts cultured from patients with familial incomplete male pseudohermaphroditism, type 2.", "content": "The activity of 5alpha-reductase, the enzyme that converts testosterone to dihydrotestosterone, has been assessed in cell-free extracts of fibroblasts grown from foreskin, labia majora, scrotum, and nongenital skin from control subjects, from patients with developmental defects of the urogenital system, drom two subjects with the type 2 form of familial incomplete male pseudohermaphroditism and from individuals with other forms of hereditary male pseudohermaphoditism. Enzyme activity was shown to be maximal in the pH range of 5 to 6. Substrate specificity studies indicated that the enzyme so assayed is the 5alpha-reductase previously characterized in human foreskin. The activity of the enzyme was low in normal fibroblasts grown from nongenital skin and high in most fibroblasts grown from genital skin. 5alpha-Reductase activity in extracts of foreskin fibroblasts from two subjects with the type 2 disorder was undetectable at pH 5.5. Activity in comparable fibroblast extracts from most patients with other forms of hereditary male pseudohermaphroditism was easily measurable.", "contents": "Diminished 5alpha-reductase activity in extracts of fibroblasts cultured from patients with familial incomplete male pseudohermaphroditism, type 2. The activity of 5alpha-reductase, the enzyme that converts testosterone to dihydrotestosterone, has been assessed in cell-free extracts of fibroblasts grown from foreskin, labia majora, scrotum, and nongenital skin from control subjects, from patients with developmental defects of the urogenital system, drom two subjects with the type 2 form of familial incomplete male pseudohermaphroditism and from individuals with other forms of hereditary male pseudohermaphoditism. Enzyme activity was shown to be maximal in the pH range of 5 to 6. Substrate specificity studies indicated that the enzyme so assayed is the 5alpha-reductase previously characterized in human foreskin. The activity of the enzyme was low in normal fibroblasts grown from nongenital skin and high in most fibroblasts grown from genital skin. 5alpha-Reductase activity in extracts of foreskin fibroblasts from two subjects with the type 2 disorder was undetectable at pH 5.5. Activity in comparable fibroblast extracts from most patients with other forms of hereditary male pseudohermaphroditism was easily measurable."}
{"id": "PMID:240820", "title": "Structural states and transitions of carp hemoglobin.", "content": "The wide ligand affinity range previously observed for carp hemoglobin is bounded at both extremes by regions of constant affinity. Within these regions, pH, organic phosphates, and the extent of ligand binding have no effect on the measured affinity and the cooperativity of ligand binding is greatly reduced or absent. The rates of CO recombination to fully and partially unliganded carp hemoglobin, under various organic phosphate and pH conditions, are shown to reflect this behavior. Constant kinetic rates are seen to directly correspond to the regions of constant affinity. Therefore, these are taken to be single protein conformations, one of high and one of low ligand affinity. In the simplest view, these conformations represent the R and T states of a two-state model, and most of the properties of carp hemoglobin are explained quite well within this framework. Increases in either hydrogen or phosphate ion concentrations favor the stabilization of the low affinity structure of even fully liganded carp hemoglobin. We have studied the structural transition from high to low affinity by monitoring the absorption spectra of carp hemoglobins at constant pH as a function of organic phosphate concentration. We find that different spectra are induced in both carp methemoglobin and cyanomethemoglobin by inositol hexaphosphate addition. Furthermore, the dependence of the magnitude of the spectral changes on pH and organic phosphate concentration is the close agreement with that predicted from studies of the ligand binding properties of the molecule.", "contents": "Structural states and transitions of carp hemoglobin. The wide ligand affinity range previously observed for carp hemoglobin is bounded at both extremes by regions of constant affinity. Within these regions, pH, organic phosphates, and the extent of ligand binding have no effect on the measured affinity and the cooperativity of ligand binding is greatly reduced or absent. The rates of CO recombination to fully and partially unliganded carp hemoglobin, under various organic phosphate and pH conditions, are shown to reflect this behavior. Constant kinetic rates are seen to directly correspond to the regions of constant affinity. Therefore, these are taken to be single protein conformations, one of high and one of low ligand affinity. In the simplest view, these conformations represent the R and T states of a two-state model, and most of the properties of carp hemoglobin are explained quite well within this framework. Increases in either hydrogen or phosphate ion concentrations favor the stabilization of the low affinity structure of even fully liganded carp hemoglobin. We have studied the structural transition from high to low affinity by monitoring the absorption spectra of carp hemoglobins at constant pH as a function of organic phosphate concentration. We find that different spectra are induced in both carp methemoglobin and cyanomethemoglobin by inositol hexaphosphate addition. Furthermore, the dependence of the magnitude of the spectral changes on pH and organic phosphate concentration is the close agreement with that predicted from studies of the ligand binding properties of the molecule."}
{"id": "PMID:240821", "title": "The enediolate analogue 5-phosphoarabinonate as a mechanistic probe for phosphoglucose isomerase.", "content": "A stable analogue has been prepared of the enediolate anion believed to occur transiently in the reaction of phosphoglucose isomerase. This compound, 5-phosphoarabinonate, is the strongest known competitive inhibitor of the enzyme (Ki = 3 times 10(-7) M below pH 7). A distinctive pH dependence of binding, also found for two other aldonic acid omega-phosphates, 6-phosphogluconate and 4-phosphoerythronate, involves pertubation of a pKa from 7.0 in the free enzyme to 9.0 in the enzyme-inhibitor complex. This perturbation may reflect a catalytically advantageous increase in basicity which occurs around the transition state of the normal enzymatic reaction.", "contents": "The enediolate analogue 5-phosphoarabinonate as a mechanistic probe for phosphoglucose isomerase. A stable analogue has been prepared of the enediolate anion believed to occur transiently in the reaction of phosphoglucose isomerase. This compound, 5-phosphoarabinonate, is the strongest known competitive inhibitor of the enzyme (Ki = 3 times 10(-7) M below pH 7). A distinctive pH dependence of binding, also found for two other aldonic acid omega-phosphates, 6-phosphogluconate and 4-phosphoerythronate, involves pertubation of a pKa from 7.0 in the free enzyme to 9.0 in the enzyme-inhibitor complex. This perturbation may reflect a catalytically advantageous increase in basicity which occurs around the transition state of the normal enzymatic reaction."}
{"id": "PMID:240822", "title": "Mechanistic implications of the pH independence of inhibition of phosphoglucose isomerase by neutral sugar phosphates.", "content": "In contrast to the strongly pH-dependent inhibition of phosphoglucose isomerase by substrate analogues with a free carboxyl group, inhibition of this enzyme by neutral sugar phosphates is essentially invariant between pH 7 and 9. Competitive inhibition constants for glucitol 6-phosphate (40 muM), arabinose 5-phosphate (50 muM), and erythritol 4-phosphate (100 muM) were found to be of the same order of magnitude as that reported previously for substrate binding constants (50 to 240 muM). The unique exception is erythrose 4-phosphate whose Ki (0.7 muM, independent of pH) reflects a tightness of binding similar to that found at pH values near or below neutrality for the transition state analogue 5-phosphorarabinonate. The pH independence of inhibition by erythrose 4-phosphate and other neutral sugar phosphates may reflect a mode and locus of binding to phosphoglucose isomerase different from that of the aldonate inhibitors.", "contents": "Mechanistic implications of the pH independence of inhibition of phosphoglucose isomerase by neutral sugar phosphates. In contrast to the strongly pH-dependent inhibition of phosphoglucose isomerase by substrate analogues with a free carboxyl group, inhibition of this enzyme by neutral sugar phosphates is essentially invariant between pH 7 and 9. Competitive inhibition constants for glucitol 6-phosphate (40 muM), arabinose 5-phosphate (50 muM), and erythritol 4-phosphate (100 muM) were found to be of the same order of magnitude as that reported previously for substrate binding constants (50 to 240 muM). The unique exception is erythrose 4-phosphate whose Ki (0.7 muM, independent of pH) reflects a tightness of binding similar to that found at pH values near or below neutrality for the transition state analogue 5-phosphorarabinonate. The pH independence of inhibition by erythrose 4-phosphate and other neutral sugar phosphates may reflect a mode and locus of binding to phosphoglucose isomerase different from that of the aldonate inhibitors."}
{"id": "PMID:240823", "title": "Some properties of mammalian cardiac cytochrome c1.", "content": "Investigations into the nature of the axial heme ligands, the strength of the heme crevice, the reactivity with cyanide, and the ascorbate reducibility of cytochrome c1 were performed to explore structure-function relationships of cytochrome c1. The existence of an absorbance band at 690 nm, which was quenched by raising the pH with a pK of 9.2 corresponding to a low spin-low transition, suggested that a methionine residue probably functioned as one of the axial heme iron ligands in this cytochrome. Spectral titrations of cytochrome c1 in the low pH range showed a markedly elevated pK for the low spin-high spin transition relative to cytochrome c. Denaturation studies with urea, the absence of any reaction with cyanide, and the evidence from other lines would appear to indicate that the heme group of cytochrome c1 was reduced by ascorbate at approximately 5% of the rate of reduction of cytochrome c but this rate dramatically increased with increasing pH concomitant with the disappearance of the 690 nm absorbance band. Circular dichroic spectra substantiated that elevated pH produced conformational changes localized to the heme crevice and probably also the regions containing aromatic residues. The enhanced rate of ascorbate reduction was perhaps a consequence of the increased accessibility of the heme iron to ascorbate. Major unfolding of the protein in 8 M urea, however, completely abolished the ascorbate reducibility of cytochrome c1. The buried nature of the heme group of cytochrome c1 would probably preclude transfer of an electron from cytochrome c1 to cytochrome c through a direct Fe-Fe or a heme-heme interaction. This poses an important question concerning the mechanism of this electron transfer between these two cytochromes not only in mitochondria but also in solution.", "contents": "Some properties of mammalian cardiac cytochrome c1. Investigations into the nature of the axial heme ligands, the strength of the heme crevice, the reactivity with cyanide, and the ascorbate reducibility of cytochrome c1 were performed to explore structure-function relationships of cytochrome c1. The existence of an absorbance band at 690 nm, which was quenched by raising the pH with a pK of 9.2 corresponding to a low spin-low transition, suggested that a methionine residue probably functioned as one of the axial heme iron ligands in this cytochrome. Spectral titrations of cytochrome c1 in the low pH range showed a markedly elevated pK for the low spin-high spin transition relative to cytochrome c. Denaturation studies with urea, the absence of any reaction with cyanide, and the evidence from other lines would appear to indicate that the heme group of cytochrome c1 was reduced by ascorbate at approximately 5% of the rate of reduction of cytochrome c but this rate dramatically increased with increasing pH concomitant with the disappearance of the 690 nm absorbance band. Circular dichroic spectra substantiated that elevated pH produced conformational changes localized to the heme crevice and probably also the regions containing aromatic residues. The enhanced rate of ascorbate reduction was perhaps a consequence of the increased accessibility of the heme iron to ascorbate. Major unfolding of the protein in 8 M urea, however, completely abolished the ascorbate reducibility of cytochrome c1. The buried nature of the heme group of cytochrome c1 would probably preclude transfer of an electron from cytochrome c1 to cytochrome c through a direct Fe-Fe or a heme-heme interaction. This poses an important question concerning the mechanism of this electron transfer between these two cytochromes not only in mitochondria but also in solution."}
{"id": "PMID:240824", "title": "A novel oligoribonuclease of Escherichia coli. I. Isolation and properties.", "content": "A new ribonuclease has been isolated from Escherichia coli. The enzyme is present in the 100,000 times g supernatant fraction and has been purified over 200-fold. Studies of the enzyme reveal that: 1. The enzyme shows a marked preference for oligoribonucleotides; indeed, the reaction rate is inversely proportional to the chain length of the substrate. The enzyme does not attack polynucleotides even at high concentrations of enzyme and has no detectable DNase activity. 2. The enzyme is stimulated strongly by Mn2+, less strongly by Mg2+, and not at all by Ca2+ and monovalent cations. 3. The enzyme is purified free of RNase I, RNase II, RNase III, polynucleotide phosphorylase, and other known ribonucleases of E. coli. The enzyme displays identical properties when isolated from mutants of E. coli that are deficient in the above ribonucleases. 4. The enzyme has a marked thermostability, a point of further distinction from RNase II.", "contents": "A novel oligoribonuclease of Escherichia coli. I. Isolation and properties. A new ribonuclease has been isolated from Escherichia coli. The enzyme is present in the 100,000 times g supernatant fraction and has been purified over 200-fold. Studies of the enzyme reveal that: 1. The enzyme shows a marked preference for oligoribonucleotides; indeed, the reaction rate is inversely proportional to the chain length of the substrate. The enzyme does not attack polynucleotides even at high concentrations of enzyme and has no detectable DNase activity. 2. The enzyme is stimulated strongly by Mn2+, less strongly by Mg2+, and not at all by Ca2+ and monovalent cations. 3. The enzyme is purified free of RNase I, RNase II, RNase III, polynucleotide phosphorylase, and other known ribonucleases of E. coli. The enzyme displays identical properties when isolated from mutants of E. coli that are deficient in the above ribonucleases. 4. The enzyme has a marked thermostability, a point of further distinction from RNase II."}
{"id": "PMID:240825", "title": "Use of N-benzoyl-L-tyrosine thiobenzyl ester as a protease substrate. Hydrolysis by alpha-chymotrypsin and subtilisin BPN.", "content": "In the course of searching for specific chromogenic substrates which might be useful in screening for protease-deficient mutants of Bacillus subtilis, we have developed a method for the synthesis of N-benzoyl-L-tyrosine thiobenzyl ester (BzTyrSBzl) in good yield. Spontaneous base hydrolysis of this thiol ester is low, but several serine proteases hydrolyze it readily. Spectrophotometric measurement of the hydrolysis of the ester in the presence of 5,5'-dithiobis(2-nitrobenzoic acid) provides a continuous assay for chymotrypsin as sensitive as any assay reported in the literature. Serine proteases which hydrolyze this substrate may be detected in polyacrylamide disc gels by incubation in the presence of nitro blue tetrazolium. Apparent Km values of 0.02 and 7 mM and kcat values of 37 S-1 and 126 S-1 were observed for the hydrolysis of BzTyrSBzl by alpha-chymotrypsin and subtilisin BPN', respectively. Additionally, 5 mM indole was observed to behave as a strict competitive inhibitor of the alpha-chymotrypsin-catalyzed hydrolysis of BzTyrSBzl but was observed to increase the maximal rate of hydrolysis of p-nitrophenyl acetate by alpha-chymotrypsin by 30%, as previously described. These data, the published data of other workers, and results from studies with molecular models of trypsin and subtilisin BPN' are used as the basis for describing more fully a secondary hydrophobic binding pocket on alpha-chymotrypsin. The pocket is immediately adjacent to the active site serine and is tentatively suggested to be composed of 4 aliphatic side chain residues and 2 glycine residues.", "contents": "Use of N-benzoyl-L-tyrosine thiobenzyl ester as a protease substrate. Hydrolysis by alpha-chymotrypsin and subtilisin BPN. In the course of searching for specific chromogenic substrates which might be useful in screening for protease-deficient mutants of Bacillus subtilis, we have developed a method for the synthesis of N-benzoyl-L-tyrosine thiobenzyl ester (BzTyrSBzl) in good yield. Spontaneous base hydrolysis of this thiol ester is low, but several serine proteases hydrolyze it readily. Spectrophotometric measurement of the hydrolysis of the ester in the presence of 5,5'-dithiobis(2-nitrobenzoic acid) provides a continuous assay for chymotrypsin as sensitive as any assay reported in the literature. Serine proteases which hydrolyze this substrate may be detected in polyacrylamide disc gels by incubation in the presence of nitro blue tetrazolium. Apparent Km values of 0.02 and 7 mM and kcat values of 37 S-1 and 126 S-1 were observed for the hydrolysis of BzTyrSBzl by alpha-chymotrypsin and subtilisin BPN', respectively. Additionally, 5 mM indole was observed to behave as a strict competitive inhibitor of the alpha-chymotrypsin-catalyzed hydrolysis of BzTyrSBzl but was observed to increase the maximal rate of hydrolysis of p-nitrophenyl acetate by alpha-chymotrypsin by 30%, as previously described. These data, the published data of other workers, and results from studies with molecular models of trypsin and subtilisin BPN' are used as the basis for describing more fully a secondary hydrophobic binding pocket on alpha-chymotrypsin. The pocket is immediately adjacent to the active site serine and is tentatively suggested to be composed of 4 aliphatic side chain residues and 2 glycine residues."}
{"id": "PMID:240826", "title": "Studies with GMP synthetase from Ehrlich ascites cells. Purification, properties, and interactions with nucleotide analogs.", "content": "GMP synthetase has been purified 57-fold from Ehrlich ascites cells. The enzyme was found to be stable and to have an approximate molecular weight of 85,000 (determined by gel filtration). Its activity was stimulated by dithiothreitol and inhibited by 2-mercaptoethanol, p-chloromercuribenzoate, and hydroxylamine. Both ammonia and glutamine could serve as amino group donors. While none of the 10 triphosphate purine and pyrimidine nucleotides studied were able to substitute for ATP as the energy donor for the reaction, all of these compounds were able to bind to the ATP site. The Ki values for CTP, beta-D-arabinofuranosyl-ATP, and 1-N6-ethenoATP were slightly lower than the Km of ATP (0.28 mM). Six monophosphate nucleotides were aminated by this enzyme. Listed in order of their substrate efficiency (Vmax/Km), they are: xanthosine 5'-phosphate(XMP) (28,000); 2'-dXMP (1,200); 8-azaXMP (320); 6-thioXMP (200); beta-D-arabinofuranosyl-XMP (72); 1-ribosyloxipurinol 5'-phosphate (0.5). 6-ThioXMP was a strong alternative substrate inhibitor with a Ki of 5 muM. The aminated products of the reaction (four studied) were competitive inhibitors with respect to XMP.", "contents": "Studies with GMP synthetase from Ehrlich ascites cells. Purification, properties, and interactions with nucleotide analogs. GMP synthetase has been purified 57-fold from Ehrlich ascites cells. The enzyme was found to be stable and to have an approximate molecular weight of 85,000 (determined by gel filtration). Its activity was stimulated by dithiothreitol and inhibited by 2-mercaptoethanol, p-chloromercuribenzoate, and hydroxylamine. Both ammonia and glutamine could serve as amino group donors. While none of the 10 triphosphate purine and pyrimidine nucleotides studied were able to substitute for ATP as the energy donor for the reaction, all of these compounds were able to bind to the ATP site. The Ki values for CTP, beta-D-arabinofuranosyl-ATP, and 1-N6-ethenoATP were slightly lower than the Km of ATP (0.28 mM). Six monophosphate nucleotides were aminated by this enzyme. Listed in order of their substrate efficiency (Vmax/Km), they are: xanthosine 5'-phosphate(XMP) (28,000); 2'-dXMP (1,200); 8-azaXMP (320); 6-thioXMP (200); beta-D-arabinofuranosyl-XMP (72); 1-ribosyloxipurinol 5'-phosphate (0.5). 6-ThioXMP was a strong alternative substrate inhibitor with a Ki of 5 muM. The aminated products of the reaction (four studied) were competitive inhibitors with respect to XMP."}
{"id": "PMID:240827", "title": "Hepatic microsomal alcohol-oxidizing system. Affinity for methanol, ethanol, propanol, and butanol.", "content": "Oxidation of methanol, ethanol, propanol, and butanol by the microsomal fraction of rat liver homogenate is described. This microsomal alcohol-oxidizing system is dependent on NADPH and molecular oxygen and is partially inhibited by CO, features which are common for microsomal drug-metabolizing enzymes. The activity of the microsomal alcohol-oxidizing system could be dissociated from the alcohol peroxidation via catalase-H2O2 by differences in substrate specificity, since higher aliphatic alcohols react only with the microsomal system, but not with catalase-H2O2. Following solubilization of microsomes by ultrasonication and treatment with deoxycholate, the activity of the microsomal alcohol-oxidizing system was separated from contaminating catalase by DEAE-cellulose column chromatography, ruling out an obligatory involvement of catalase-H2O2 in the activity of the NADPH-dependent microsomal alcohol-oxidizing system. In intact hepatic microsomes, the catalase inhibitor sodium azide slightly decreased the oxidation of methanol and ethanol, but not that of propanol and butanol, indicating a facultative role of contaminating catalase in the microsomal oxidation of lower aliphatic alcohols only. It is suggested that the microsomal alcohol-oxidizing system accounts, at least in part, for that fraction of hepatic alcohol metabolism which is independent of the pathway involving alcohol dehydrogenase activity.", "contents": "Hepatic microsomal alcohol-oxidizing system. Affinity for methanol, ethanol, propanol, and butanol. Oxidation of methanol, ethanol, propanol, and butanol by the microsomal fraction of rat liver homogenate is described. This microsomal alcohol-oxidizing system is dependent on NADPH and molecular oxygen and is partially inhibited by CO, features which are common for microsomal drug-metabolizing enzymes. The activity of the microsomal alcohol-oxidizing system could be dissociated from the alcohol peroxidation via catalase-H2O2 by differences in substrate specificity, since higher aliphatic alcohols react only with the microsomal system, but not with catalase-H2O2. Following solubilization of microsomes by ultrasonication and treatment with deoxycholate, the activity of the microsomal alcohol-oxidizing system was separated from contaminating catalase by DEAE-cellulose column chromatography, ruling out an obligatory involvement of catalase-H2O2 in the activity of the NADPH-dependent microsomal alcohol-oxidizing system. In intact hepatic microsomes, the catalase inhibitor sodium azide slightly decreased the oxidation of methanol and ethanol, but not that of propanol and butanol, indicating a facultative role of contaminating catalase in the microsomal oxidation of lower aliphatic alcohols only. It is suggested that the microsomal alcohol-oxidizing system accounts, at least in part, for that fraction of hepatic alcohol metabolism which is independent of the pathway involving alcohol dehydrogenase activity."}
{"id": "PMID:240828", "title": "Nuclear magnetic resonance titration curves of histidine ring protons. The effect of temperature on ribonuclease A.", "content": "The ionization constants of 3 of the histidine residues of ribonuclease A have beenobtained at 5 temperatures from the nuclear magnetic resonance titration curves of the imidazole C2 proton resonances. Thermodynamic parameters derived from the ionization constants indicate that histidine residues 105 and 119 are fairly well exposed to solvent, while histidine residue 12 is in a somewhat more restricted environment. Measurements of the low pH inflection present in the titration curve of histidine-12 yield a large negative entropy value, indicating that the group givine rise to this inflection is also buried.", "contents": "Nuclear magnetic resonance titration curves of histidine ring protons. The effect of temperature on ribonuclease A. The ionization constants of 3 of the histidine residues of ribonuclease A have beenobtained at 5 temperatures from the nuclear magnetic resonance titration curves of the imidazole C2 proton resonances. Thermodynamic parameters derived from the ionization constants indicate that histidine residues 105 and 119 are fairly well exposed to solvent, while histidine residue 12 is in a somewhat more restricted environment. Measurements of the low pH inflection present in the titration curve of histidine-12 yield a large negative entropy value, indicating that the group givine rise to this inflection is also buried."}
{"id": "PMID:240829", "title": "Nuclear magnetic resonance titration curves of histidine ring protons. Human metmyoglobin and the effects of azide on human, horse, and sperm whale metmyoglobins.", "content": "Four titrating histidine ring C2 and C4 proton resonances are observed in 220 MHz proton NMR spectra of human metmyoglobin as a function of pH. Values of ionization constants determined from the NMR titration data using an equation describing a simple proton association-dissociation equilibrium are curves (1) 6.6, (2) 7.0, (3) 5.8, and (4) 7.4. Four histidine residues have also been found to be solvent-accessible in human metmyoglobin by carboxymethylation studies (Harris, C.M., and Hill, R.L. (1969) J. Biol. Chem. 244, 2195-2203). Two of the titration curves (3 and 4) deviate significantly from the chemical shift values normally observed for histidine C2 proton resonances. Curve 3, with a low pKa, is shifted downfield at high values of pH and also exhibits a second minor inflection with a pKa value of 8.8. On the other hand, the high pKa curve, 4, is shifted upfield at all values of pH. The characteristics of the NMR titration curves with the lowest and highest pKa values (3 and4) are very similar to curves observed previously with sperm whale and horse metmyoglobins (Cohen, J.S., Hagenmaier, H., Pollard, H., and Schechter, A.N. (1972) J. Mol. Biol. 71, 513-519). These results indicate that the histidine residues from which these curves are derived have unusual and characteristic environments in this series of homologous proteins. The NMR spectra of all three metmyoglobins are changed extensively as a result of azide ion binding, indicating conformational changes affecting the environments of several imidazole side chains. The presence of azide ion causes a selective downfield chemical shift for the low pKa curve and a selective upfield chemical shift for the high pKa curve in all three proteins. Azide also abolishes the second inflection seen in the low pKa curve at high pH. In addition to these effects, the presence of azide ion permits the observation of two additional titrating proton resonances for all three metmyoglobins. Increasing the azide to protein ratio at several fixed values of pH yields results which show that a slow exchange process is occurring with each of the metmyoglobins. In the azide titration studies the maximum changes in the NMR spectra occurred at approximately equimolar concentrations. The NMR results for these proteins in the absence and presence of azide ion are related to x-ray crystallographic studies of sperm whale metmyoglobin and the known alkylation properties of the histidine residues. Tentative assignments of the titrating resonances observed are suggested.", "contents": "Nuclear magnetic resonance titration curves of histidine ring protons. Human metmyoglobin and the effects of azide on human, horse, and sperm whale metmyoglobins. Four titrating histidine ring C2 and C4 proton resonances are observed in 220 MHz proton NMR spectra of human metmyoglobin as a function of pH. Values of ionization constants determined from the NMR titration data using an equation describing a simple proton association-dissociation equilibrium are curves (1) 6.6, (2) 7.0, (3) 5.8, and (4) 7.4. Four histidine residues have also been found to be solvent-accessible in human metmyoglobin by carboxymethylation studies (Harris, C.M., and Hill, R.L. (1969) J. Biol. Chem. 244, 2195-2203). Two of the titration curves (3 and 4) deviate significantly from the chemical shift values normally observed for histidine C2 proton resonances. Curve 3, with a low pKa, is shifted downfield at high values of pH and also exhibits a second minor inflection with a pKa value of 8.8. On the other hand, the high pKa curve, 4, is shifted upfield at all values of pH. The characteristics of the NMR titration curves with the lowest and highest pKa values (3 and4) are very similar to curves observed previously with sperm whale and horse metmyoglobins (Cohen, J.S., Hagenmaier, H., Pollard, H., and Schechter, A.N. (1972) J. Mol. Biol. 71, 513-519). These results indicate that the histidine residues from which these curves are derived have unusual and characteristic environments in this series of homologous proteins. The NMR spectra of all three metmyoglobins are changed extensively as a result of azide ion binding, indicating conformational changes affecting the environments of several imidazole side chains. The presence of azide ion causes a selective downfield chemical shift for the low pKa curve and a selective upfield chemical shift for the high pKa curve in all three proteins. Azide also abolishes the second inflection seen in the low pKa curve at high pH. In addition to these effects, the presence of azide ion permits the observation of two additional titrating proton resonances for all three metmyoglobins. Increasing the azide to protein ratio at several fixed values of pH yields results which show that a slow exchange process is occurring with each of the metmyoglobins. In the azide titration studies the maximum changes in the NMR spectra occurred at approximately equimolar concentrations. The NMR results for these proteins in the absence and presence of azide ion are related to x-ray crystallographic studies of sperm whale metmyoglobin and the known alkylation properties of the histidine residues. Tentative assignments of the titrating resonances observed are suggested."}
{"id": "PMID:240830", "title": "Mechanism of action of bovine testicular hyaluronidase. Mapping of the active site.", "content": "The reactions of purified, homogeneous bovine testicular hyaluronidase have been studied with radioactively labeled oligomers of hyalobiuronic acid, (GlcUA-GlcNAc)n, as substrates and acceptors. Transglycosylation occurs by transfer of a glycosyl residue with retention of configuration from a leaving group to an acceptor. On the basis of detailed examination of cleavage and transglycosylation patterns for the trimer; comparison of trimer, tetramer, and polymer as substrates; comparison of acceptors; equilibrium binding; and other data, it is proposed that the enzyme's active site consists of five subsites for hyalobiuronate residues. In the terminology of Schechter, I., and Berger, A. ((1966) Biochemistry 5, 3371), these are s2-s1-s' 2-s3, where the reducing terminus is to the right, and cleavage occurs between s1 and s' 1. It is proposed that subsite s'2 has a high affinity for a substrate residue, while s1 and s'1 have low substrate affinity, and s2 and s' 3 are intermediate in affinity. This proposal is seen to have mechanistic implications. The reactions of several substrates show similar bell-shaped pH dependences, with optima in the region of pH 5 to 5.5.", "contents": "Mechanism of action of bovine testicular hyaluronidase. Mapping of the active site. The reactions of purified, homogeneous bovine testicular hyaluronidase have been studied with radioactively labeled oligomers of hyalobiuronic acid, (GlcUA-GlcNAc)n, as substrates and acceptors. Transglycosylation occurs by transfer of a glycosyl residue with retention of configuration from a leaving group to an acceptor. On the basis of detailed examination of cleavage and transglycosylation patterns for the trimer; comparison of trimer, tetramer, and polymer as substrates; comparison of acceptors; equilibrium binding; and other data, it is proposed that the enzyme's active site consists of five subsites for hyalobiuronate residues. In the terminology of Schechter, I., and Berger, A. ((1966) Biochemistry 5, 3371), these are s2-s1-s' 2-s3, where the reducing terminus is to the right, and cleavage occurs between s1 and s' 1. It is proposed that subsite s'2 has a high affinity for a substrate residue, while s1 and s'1 have low substrate affinity, and s2 and s' 3 are intermediate in affinity. This proposal is seen to have mechanistic implications. The reactions of several substrates show similar bell-shaped pH dependences, with optima in the region of pH 5 to 5.5."}
{"id": "PMID:240831", "title": "Nicotinamide adenine dinucleotide glycohydrolase from rat liver nuclei. Isolation and characterization of a new enzyme.", "content": "A new type of nicotinamide adenine dinucleotide glycohydrolase (NADase) has been isolated from rat liver nuclei. When partially purified chromatin is passed through a Sephadex G-200 column in the presence of 1 M NaCl, enzyme activities catalyzing the liberation of nicotinamide from NAD elute in two peaks. One, which appears in the void volume fraction, hydrolyzes the nicotinamide-ribose linkage of NAD to produce nicotinamide and ADP-ribose in stoichiometric amounts. This activity is not inhibited by 5 mM nicotinamide. The other, which elutes much later, catalyzes the formation of poly(ADP-ribose) from NAD and is completely inhibited by 5 mM nicotinamide. The former, NADase, is DNase-insensitive and thermostable, has a pH optimum of 6.5 to 7, a Km for NAD of 28 muM, and a Ki for nicotinamide of 80 mM, and hydrolyzes NADP as well as NAD. The latter, poly(ADP-ribose) synthetase, is sensitive to DNase treatment and heat labile, has a pH optimum of 8 to 8.5, a Km for NAD of 250 muM and a Ki for nicotinamide of 0.5 mM and is strictly specific for NAD. Further, the former NADase is shown to lack transglycosidase activity, which has been documented to be a general property of NADases derived from animal tissues. These results indicate that the NAD-hydrolyzing enzyme newly isolated from nuclei is a novel type of mammalian NADase which catalyzes the hydrolytic cleavage of the nicotinamide-ribose linkage of NAD.", "contents": "Nicotinamide adenine dinucleotide glycohydrolase from rat liver nuclei. Isolation and characterization of a new enzyme. A new type of nicotinamide adenine dinucleotide glycohydrolase (NADase) has been isolated from rat liver nuclei. When partially purified chromatin is passed through a Sephadex G-200 column in the presence of 1 M NaCl, enzyme activities catalyzing the liberation of nicotinamide from NAD elute in two peaks. One, which appears in the void volume fraction, hydrolyzes the nicotinamide-ribose linkage of NAD to produce nicotinamide and ADP-ribose in stoichiometric amounts. This activity is not inhibited by 5 mM nicotinamide. The other, which elutes much later, catalyzes the formation of poly(ADP-ribose) from NAD and is completely inhibited by 5 mM nicotinamide. The former, NADase, is DNase-insensitive and thermostable, has a pH optimum of 6.5 to 7, a Km for NAD of 28 muM, and a Ki for nicotinamide of 80 mM, and hydrolyzes NADP as well as NAD. The latter, poly(ADP-ribose) synthetase, is sensitive to DNase treatment and heat labile, has a pH optimum of 8 to 8.5, a Km for NAD of 250 muM and a Ki for nicotinamide of 0.5 mM and is strictly specific for NAD. Further, the former NADase is shown to lack transglycosidase activity, which has been documented to be a general property of NADases derived from animal tissues. These results indicate that the NAD-hydrolyzing enzyme newly isolated from nuclei is a novel type of mammalian NADase which catalyzes the hydrolytic cleavage of the nicotinamide-ribose linkage of NAD."}
{"id": "PMID:240832", "title": "Kinetic and binding studies of Mn (II) and fructose 1,6-bisphosphate with rabbit liver hexosebisphosphatase.", "content": "The separate interaction of the substrate fructose 1,6-bisphosphate and a metal ion cofactor Mn2+ with neutral hexosebisphosphatase has been studied under equilibrium conditions at pH 7.5 with gel filtration and electron paramagnetic resonance measurements, respectively. Binding data for both ligands to the enzyme yielded nonlinear Scatchard plots that analyze in terms of four negatively cooperative binding sites per enzyme tetramer. Graphical estimates of the binding constants were refined by a computer searching procedure and nonlinear least squares analysis. These results are qualitatively similar to those obtained from binding studies involving teh alkaline enzyme, a modified form of hexosebisphosphatase whose pH optimum is in the alkaline pH region. Both forms of the enzyme enhance the proton relaxation rate of water protons by a factor of approximately 7 to 8 at 24 MHz, demonstrating similar metal ion environments. Teh activator Co(III)-EDTA did not affect Mn2+ binding to the neutral enzyme. In the presence of (alpha + beta)methyl-D-fructofuranoside 1,6-bisphosphate, however, two sets--each containing four Mn2+ binding sites--were observed per enzyme tetramer with loss of the negatively cooperative interaction. These results are viewed in terms of four noncatalytic and four catalytic Mn2+ binding sites. Parallel kinetic investigations were conducted on the neutral enzyme to determine specific activity as a function of Mn2+ and fructose 1,6-bisphosphate concentration. A pro-equilibrium sequential pathway model involving Mn2+-enzyme and the Mn2+-fructose 1,6-bisphosphate complex both as substrate and as an allosteric inhibitor satisfactorily fit the kinetic observations. All possible enzyme species were computed from the determined binding constants and grouped according to the number of moles of Mn2+-fructose 1,6-bisphosphate complex bound to the Mn2+-enzyme, and individual rate constants were calculated. The testing of other models and their failure to describe the kinetic observations are discussed.", "contents": "Kinetic and binding studies of Mn (II) and fructose 1,6-bisphosphate with rabbit liver hexosebisphosphatase. The separate interaction of the substrate fructose 1,6-bisphosphate and a metal ion cofactor Mn2+ with neutral hexosebisphosphatase has been studied under equilibrium conditions at pH 7.5 with gel filtration and electron paramagnetic resonance measurements, respectively. Binding data for both ligands to the enzyme yielded nonlinear Scatchard plots that analyze in terms of four negatively cooperative binding sites per enzyme tetramer. Graphical estimates of the binding constants were refined by a computer searching procedure and nonlinear least squares analysis. These results are qualitatively similar to those obtained from binding studies involving teh alkaline enzyme, a modified form of hexosebisphosphatase whose pH optimum is in the alkaline pH region. Both forms of the enzyme enhance the proton relaxation rate of water protons by a factor of approximately 7 to 8 at 24 MHz, demonstrating similar metal ion environments. Teh activator Co(III)-EDTA did not affect Mn2+ binding to the neutral enzyme. In the presence of (alpha + beta)methyl-D-fructofuranoside 1,6-bisphosphate, however, two sets--each containing four Mn2+ binding sites--were observed per enzyme tetramer with loss of the negatively cooperative interaction. These results are viewed in terms of four noncatalytic and four catalytic Mn2+ binding sites. Parallel kinetic investigations were conducted on the neutral enzyme to determine specific activity as a function of Mn2+ and fructose 1,6-bisphosphate concentration. A pro-equilibrium sequential pathway model involving Mn2+-enzyme and the Mn2+-fructose 1,6-bisphosphate complex both as substrate and as an allosteric inhibitor satisfactorily fit the kinetic observations. All possible enzyme species were computed from the determined binding constants and grouped according to the number of moles of Mn2+-fructose 1,6-bisphosphate complex bound to the Mn2+-enzyme, and individual rate constants were calculated. The testing of other models and their failure to describe the kinetic observations are discussed."}
{"id": "PMID:240833", "title": "Acidic protease from human seminal plasma. Purification and some properties of active enzyme and of proenzyme.", "content": "A procedure to purify to homogeneity the active form as well as the proenzyme form of the acidic protease of human seminal plasma is described. This involved precipitation with ammonium sulfate, chromatography on diethylaminoethylcellulose, Sephadex G-200, and Sephadex G-100. The molecular weights of the active form and of the proenzyme were determined by electrophoresis and gel filtration to be 35,000 and 42,000, respectively. The proenzyme was more stable than the active form in alkaline solution and can be converted into the active enzyme under acidic conditions. The active form of the acidic protease can hydrolyze hemoglobin, N,N'-dimethylcasein, N-acetyl-L-phenylalanyl-L-diiodotyrosine, and N-benzyloxycarbonyl-L-glutamyl-L-phenylalanine, but cannot hydrolyze bovine serum albumin, ovalbumin, N-benzyloxycarbonyl-L-glutamyl-L-tyrosine. The active form was also inhibited by p-bromophenacyl bromide and 1,2-epoxy-3-(p-nitrophenoxy)propane.", "contents": "Acidic protease from human seminal plasma. Purification and some properties of active enzyme and of proenzyme. A procedure to purify to homogeneity the active form as well as the proenzyme form of the acidic protease of human seminal plasma is described. This involved precipitation with ammonium sulfate, chromatography on diethylaminoethylcellulose, Sephadex G-200, and Sephadex G-100. The molecular weights of the active form and of the proenzyme were determined by electrophoresis and gel filtration to be 35,000 and 42,000, respectively. The proenzyme was more stable than the active form in alkaline solution and can be converted into the active enzyme under acidic conditions. The active form of the acidic protease can hydrolyze hemoglobin, N,N'-dimethylcasein, N-acetyl-L-phenylalanyl-L-diiodotyrosine, and N-benzyloxycarbonyl-L-glutamyl-L-phenylalanine, but cannot hydrolyze bovine serum albumin, ovalbumin, N-benzyloxycarbonyl-L-glutamyl-L-tyrosine. The active form was also inhibited by p-bromophenacyl bromide and 1,2-epoxy-3-(p-nitrophenoxy)propane."}
{"id": "PMID:240834", "title": "Biosynthesis of bacterial glycogen. Kinetic studies of a glucose-1-phosphate adenylyltransferase (EC 2.7.7.27) from a glycogen-deficient mutant of Escherichia coli B.", "content": "An Escherichia coli B mutant, SG14, accumulates glycogen at 28% the rate observed for the parent E. coli B strain. The glycogen accumulated in the mutant is similar to the glycogen isolated from the parent strain with respect to alpha- and beta-amylosis, chain length determination, and I2-complex absorption spectra. The SG14 mutant contains normal glycogen synthase and branching enzyme activity but has an ADP-glucose pyrophosphorylase with altered kinetic and allosteric properties. The mutant enzyme has been partially purified and requires a 12-fold higher concentration of fructose-P2 or a 26 fold higher concentration of pyridoxal-P than the parent type enzyme for 50% of maximal allosteric activation. TPNH, an effective activator of the E. coli B enzyme, does not activate the SG14 ADP-glucose pyrophosphorylase. Other studies show that for the SG14 enzyme the concentrations of ATP and Mg2+ in the synthesis direction and the concentrations of ADP-glucose and PPi in the pyrophosphorolysis direction required to give 50% of maximal activity are 3- to 6-fold higher than those observed for the parent E. coli B ADP-glucose pyrophosphorylase. The Km for alpha-glucose-1-P at saturating to half-saturating concentrations of the activator, fructose-P2, are about the same for both enzymes. However, in the presence of no activator, the concentration of glucose-1-P required for half-maximal activity is about 1.8-fold higher for the SG14 enzyme. Thus SG14 ADP-glucose pyrophosphorylase has lower affinity for its substrates than does the parent enzyme. Previously the SG14 enzyme had been shown to be less sensitive to inhibition by 5'-AMP than the E. coli B enzyme. This ensensitivity to inhibition renders the SG14 enzyme less responsive to energy charge than the E. coli B ADP-glucose pyrophosphorylase. On the basis of the above results and taking into account the reported concentrations of fructose-P2, of pyridoxal-P, and of the adenine nucleotide pool and its energy charge in E. coli strains, it is concluded that furctose-P2 is the important physiological allosteric activator of E. coli ADP-glucose pyrophosphorylase. Furthermore, the 1.7-fold increased rate of accumulation of glycogen observed when E. coli B or SG14 shifts from exponential phase to stationary phase of growth in nitrogen-limiting media can be accounted for by the 2.4-fold increase of the levels of the glycogen biosynthetic enzymes, glycogen synthase, and ADP-glucose pyrophosphorylase. Thus both allosteric regulation of the ADP-glucose pyrophosphorylase as well as the genetic regulation of the biosynthesis of the glycogen biosynthetic enzymes are involved in the regulation of glycogen accumulation in E. coli B.", "contents": "Biosynthesis of bacterial glycogen. Kinetic studies of a glucose-1-phosphate adenylyltransferase (EC 2.7.7.27) from a glycogen-deficient mutant of Escherichia coli B. An Escherichia coli B mutant, SG14, accumulates glycogen at 28% the rate observed for the parent E. coli B strain. The glycogen accumulated in the mutant is similar to the glycogen isolated from the parent strain with respect to alpha- and beta-amylosis, chain length determination, and I2-complex absorption spectra. The SG14 mutant contains normal glycogen synthase and branching enzyme activity but has an ADP-glucose pyrophosphorylase with altered kinetic and allosteric properties. The mutant enzyme has been partially purified and requires a 12-fold higher concentration of fructose-P2 or a 26 fold higher concentration of pyridoxal-P than the parent type enzyme for 50% of maximal allosteric activation. TPNH, an effective activator of the E. coli B enzyme, does not activate the SG14 ADP-glucose pyrophosphorylase. Other studies show that for the SG14 enzyme the concentrations of ATP and Mg2+ in the synthesis direction and the concentrations of ADP-glucose and PPi in the pyrophosphorolysis direction required to give 50% of maximal activity are 3- to 6-fold higher than those observed for the parent E. coli B ADP-glucose pyrophosphorylase. The Km for alpha-glucose-1-P at saturating to half-saturating concentrations of the activator, fructose-P2, are about the same for both enzymes. However, in the presence of no activator, the concentration of glucose-1-P required for half-maximal activity is about 1.8-fold higher for the SG14 enzyme. Thus SG14 ADP-glucose pyrophosphorylase has lower affinity for its substrates than does the parent enzyme. Previously the SG14 enzyme had been shown to be less sensitive to inhibition by 5'-AMP than the E. coli B enzyme. This ensensitivity to inhibition renders the SG14 enzyme less responsive to energy charge than the E. coli B ADP-glucose pyrophosphorylase. On the basis of the above results and taking into account the reported concentrations of fructose-P2, of pyridoxal-P, and of the adenine nucleotide pool and its energy charge in E. coli strains, it is concluded that furctose-P2 is the important physiological allosteric activator of E. coli ADP-glucose pyrophosphorylase. Furthermore, the 1.7-fold increased rate of accumulation of glycogen observed when E. coli B or SG14 shifts from exponential phase to stationary phase of growth in nitrogen-limiting media can be accounted for by the 2.4-fold increase of the levels of the glycogen biosynthetic enzymes, glycogen synthase, and ADP-glucose pyrophosphorylase. Thus both allosteric regulation of the ADP-glucose pyrophosphorylase as well as the genetic regulation of the biosynthesis of the glycogen biosynthetic enzymes are involved in the regulation of glycogen accumulation in E. coli B."}
{"id": "PMID:240835", "title": "Metal ion binding in triclinic lysozyme.", "content": "The binding sites of Mn2+, Co2+, and Gd3+ have been determined in triclinic lysozyme at pH 4.5 to 4.6. Mn2+ and Co2+ bind a site approximately 2.5 A from 1 of the oxygen atoms of the Glu-35 chain. The occupancy of the Mn2+ site is 0.22, corresponding to 1 bound ion for each 4.6 protein molecules. The occupancy of the Co2+ site is much lower, about 0.048. Gd3+ appears to be bound at two sites, the main one 2.5 A from an oxygen atom of the Glu-35 side chain, the other 3.1 A from an oxygen atom of the Asp-52 chain. The occupancy of both Gd3+ sites is low, 0.036 and 0.016, the latter being so low that the presence of the ion at this site is in doubt. The binding site of Mn2+ in the di(N-acetylglucosamine)-lysozyme complex has also been determined. It does not differ significantly from the Mn2+ binding site in the native protein, but the occupancy is lower, 0.16.", "contents": "Metal ion binding in triclinic lysozyme. The binding sites of Mn2+, Co2+, and Gd3+ have been determined in triclinic lysozyme at pH 4.5 to 4.6. Mn2+ and Co2+ bind a site approximately 2.5 A from 1 of the oxygen atoms of the Glu-35 chain. The occupancy of the Mn2+ site is 0.22, corresponding to 1 bound ion for each 4.6 protein molecules. The occupancy of the Co2+ site is much lower, about 0.048. Gd3+ appears to be bound at two sites, the main one 2.5 A from an oxygen atom of the Glu-35 side chain, the other 3.1 A from an oxygen atom of the Asp-52 chain. The occupancy of both Gd3+ sites is low, 0.036 and 0.016, the latter being so low that the presence of the ion at this site is in doubt. The binding site of Mn2+ in the di(N-acetylglucosamine)-lysozyme complex has also been determined. It does not differ significantly from the Mn2+ binding site in the native protein, but the occupancy is lower, 0.16."}
{"id": "PMID:240836", "title": "Characterization of an active transport system for calcium in inverted membrane vesicles of Escherichia coli.", "content": "The energy-dependent uptake of calcium by inverted membrane vesicles of Escherichia coli was investigated. Methods for preparation and storage of the vesicles were devised to allow for the maximal activity and stability of the calcium transport system. The pH and temperature optima for the reaction were observed to occur at pH 8.0 AND 30 DEGREES, RESPECTIVELY. The eft was found that the extent of the reaction depended on the presence of phosphate or oxalate. Phosphate was found to enter the vesicles at a rate slower than that of calcium. A Ca2+:Pi ratio of approximately 1.5 was found, suggesting formation of Ca3(PO4)2. Monovalent cations stimulated calcium uptake, with the order of effectiveness being K+ is greater than Na+ is greater than Li+ is greater than NH4+. Inhibition was found with certain divalent cations, but these also inhibited the electron transport chain. Of the divalent cations examined only Mg2+ and Sr2+ inhibited calcium transport without a corresponding inhibition of respiration. Calcium transport exhibited biphasic Kinetics, with a low affinity system and a high affinity system. The low affinity system showed a Km of 0.34 mM and a Vmax of 85 nmol/min/mg of protein. The kinetic constants of the high affinity system were 4.5 muM and 2 nmol/min/mg of protein. The energy for calcium transport could be derived from the electron transport chain by oxidation of NADH, D-lactate, and succinate, in order of their effectiveness. Respiration-driven calcium transport was inhibited by inhibitors of the electron transport chain and by uncouplers of oxidative phosphorylation. ATP could also be used to supply enerty for calcium transport. The ATP-driven reaction was inhibited by inhibitors of the Mg2+ATPase and by an antiserum prepared against that protein, demonstrating that that enzyme is involved in the utilization of ATP for active transport in inverted vesicles.", "contents": "Characterization of an active transport system for calcium in inverted membrane vesicles of Escherichia coli. The energy-dependent uptake of calcium by inverted membrane vesicles of Escherichia coli was investigated. Methods for preparation and storage of the vesicles were devised to allow for the maximal activity and stability of the calcium transport system. The pH and temperature optima for the reaction were observed to occur at pH 8.0 AND 30 DEGREES, RESPECTIVELY. The eft was found that the extent of the reaction depended on the presence of phosphate or oxalate. Phosphate was found to enter the vesicles at a rate slower than that of calcium. A Ca2+:Pi ratio of approximately 1.5 was found, suggesting formation of Ca3(PO4)2. Monovalent cations stimulated calcium uptake, with the order of effectiveness being K+ is greater than Na+ is greater than Li+ is greater than NH4+. Inhibition was found with certain divalent cations, but these also inhibited the electron transport chain. Of the divalent cations examined only Mg2+ and Sr2+ inhibited calcium transport without a corresponding inhibition of respiration. Calcium transport exhibited biphasic Kinetics, with a low affinity system and a high affinity system. The low affinity system showed a Km of 0.34 mM and a Vmax of 85 nmol/min/mg of protein. The kinetic constants of the high affinity system were 4.5 muM and 2 nmol/min/mg of protein. The energy for calcium transport could be derived from the electron transport chain by oxidation of NADH, D-lactate, and succinate, in order of their effectiveness. Respiration-driven calcium transport was inhibited by inhibitors of the electron transport chain and by uncouplers of oxidative phosphorylation. ATP could also be used to supply enerty for calcium transport. The ATP-driven reaction was inhibited by inhibitors of the Mg2+ATPase and by an antiserum prepared against that protein, demonstrating that that enzyme is involved in the utilization of ATP for active transport in inverted vesicles."}
{"id": "PMID:240837", "title": "Alkyl isocyanates as active site-directed inactivators of guinea pig liver transglutaminase.", "content": "Alkyl isocyanates are effective inactivators of guinea pig liver transglutaminase. Based on the specificity of the reaction the protection against inactivation by glutamine substrate, and the essential nature of calcium for the inactivation reaction, it is concluded that these reagents act as amide substrate analogs and, thus function in an active site-specific manner. Support for the contention that inactivation results from alkyl thiocarbamate ester formation through the single active site sulfhydryl group of the enzyme is (a) the loss of one free--SH group and the incorporation of 1 mol of reagent/mol of enzyme in the reaction, (b) similarity in chemical properties of the inactive enzyme derivative formed to those previously reported for another alkyl thiocarbamoylenzyme and an alkyl thiocarbamoylcysteine derivative, and (c) the finding that labeled peptides from digests of [methyl-14C]thiocarbamoyltransglutaminase and those from digests of iodoacetamide-inactivated enzyme occupy similar positions on peptide maps. Transglutaminase was found to be inactivated neither by urethan anlogs of its active ester substrates nor by urea analogs of its amide substrates. It is concluded on the basis of these findings that inactive carbamoylenzyme derivatives are formed only by direct addition of the transglutaminase active--SH group to the isocyanate C--N double bond, and not, like several serine active site enzymes, by nucleophilic displacement with urethan analogs of substrate, or by nucleophilic displacement with urea analogs of substrate.", "contents": "Alkyl isocyanates as active site-directed inactivators of guinea pig liver transglutaminase. Alkyl isocyanates are effective inactivators of guinea pig liver transglutaminase. Based on the specificity of the reaction the protection against inactivation by glutamine substrate, and the essential nature of calcium for the inactivation reaction, it is concluded that these reagents act as amide substrate analogs and, thus function in an active site-specific manner. Support for the contention that inactivation results from alkyl thiocarbamate ester formation through the single active site sulfhydryl group of the enzyme is (a) the loss of one free--SH group and the incorporation of 1 mol of reagent/mol of enzyme in the reaction, (b) similarity in chemical properties of the inactive enzyme derivative formed to those previously reported for another alkyl thiocarbamoylenzyme and an alkyl thiocarbamoylcysteine derivative, and (c) the finding that labeled peptides from digests of [methyl-14C]thiocarbamoyltransglutaminase and those from digests of iodoacetamide-inactivated enzyme occupy similar positions on peptide maps. Transglutaminase was found to be inactivated neither by urethan anlogs of its active ester substrates nor by urea analogs of its amide substrates. It is concluded on the basis of these findings that inactive carbamoylenzyme derivatives are formed only by direct addition of the transglutaminase active--SH group to the isocyanate C--N double bond, and not, like several serine active site enzymes, by nucleophilic displacement with urethan analogs of substrate, or by nucleophilic displacement with urea analogs of substrate."}
{"id": "PMID:240838", "title": "Nonequivalent binding sites in cystathionase. Nanosecond and steady fluorescence studies.", "content": "The analogs P-pyridoxyl-L-alanine and P-pyridoxyl-L-homoserine bind to the apoprotein of the enzyme cystathionase and inhibit the reactivation of enzymatic activity after addition of pyridoxyl-5-P. The binding of the inhibitors was monitored by measuring the fluorescence emitted by the P-pyridoxyl moiety at 395 nm (excitation 325 nm). The fluorometric titration results indicate the presence of nonequivalent binding sites in the apoprotein. A model based on two classes of independent binding sites fits the fluorometric data reasonably well. The presence of nonequivalent fluorescent sites in reduced cystathionase was also detected by nanosecond spectroscopy. In contrast to the model compound P-pyridoxyl-epsilon-lysine (tau equals 2.6 ns), the P-pyridoxyl residues of cystathionase display multiexponential fluorescence decay. Two fluorescence lifetimes (tau2 equals 4.1 ns and tau2 equals 15 ns) fit the deconvoluted decay results obtained by pulse fluorimetry. It is proposed that the P-pyridoxyl chromophores of reduced cystathionase have different environments.", "contents": "Nonequivalent binding sites in cystathionase. Nanosecond and steady fluorescence studies. The analogs P-pyridoxyl-L-alanine and P-pyridoxyl-L-homoserine bind to the apoprotein of the enzyme cystathionase and inhibit the reactivation of enzymatic activity after addition of pyridoxyl-5-P. The binding of the inhibitors was monitored by measuring the fluorescence emitted by the P-pyridoxyl moiety at 395 nm (excitation 325 nm). The fluorometric titration results indicate the presence of nonequivalent binding sites in the apoprotein. A model based on two classes of independent binding sites fits the fluorometric data reasonably well. The presence of nonequivalent fluorescent sites in reduced cystathionase was also detected by nanosecond spectroscopy. In contrast to the model compound P-pyridoxyl-epsilon-lysine (tau equals 2.6 ns), the P-pyridoxyl residues of cystathionase display multiexponential fluorescence decay. Two fluorescence lifetimes (tau2 equals 4.1 ns and tau2 equals 15 ns) fit the deconvoluted decay results obtained by pulse fluorimetry. It is proposed that the P-pyridoxyl chromophores of reduced cystathionase have different environments."}
{"id": "PMID:240839", "title": "Protease II from Escherichia coli. Purification and characterization.", "content": "We have previously demonstrated the existence of two types of endopeptidase in Escherichia coli. A purification procedure is described for one of these, designated protease II. It has been purified about 13,500-fold with a recovery of 24%. The isolated enzyme appears homogeneous by electrophoresis and gel filtration. Its molecular weight is estimated by three different methods to be about 58,000. Its optimal pH is around 8. Protease II activity is unaffected by chelating agents and sulfhydryl reagents. Amidase and proteolytic activities are stimulated by calcium ion, which decreases the enzyme stability. Like pancreatic trypsin, this endopeptidase catalyses the hydrolysis of alpha-amino-substituted lysine and arginine esters. It appears distinct from the previously isolated protease I, which is a chymotrypsin-like enzyme. The apparent Michaelis constant for hydrolysis of N-benzoyl-L-arginine ethyl ester is 4.7 X 10(-4) M. The esterase activity is inhibited by diisopryopylphosphorofluoridate (Ki(app) equals 2.7 X 10(-3) M) and tosyl lysine chloromethyl ketone (Ki(app) equals 1.8 X 10(-5) M), indicating that serine and histidine residues may be present in the active site. However, protease II is insensitive to phenylmethanesulfonyl fluoride and several natural trypsin inhibitors. Its amidase and esterase activities are competitively inhibited by free arginine and aromatic amidines. The proteolytic activity measured on axocasein is very low. In contrast to trypsin, protease II is without effect on native beta-galactosidase. It easily degrades aspartokinase I and III. Nevertheless both enzymes are resistant to proteolysis in the presence of their respective allosteric effectors. These results provide further evidence that such differences in protease susceptibility can be related to the conformational state of the substrate. The possible implication of structural changes in the mechanism of preferential proteolysis in vivo, is discussed.", "contents": "Protease II from Escherichia coli. Purification and characterization. We have previously demonstrated the existence of two types of endopeptidase in Escherichia coli. A purification procedure is described for one of these, designated protease II. It has been purified about 13,500-fold with a recovery of 24%. The isolated enzyme appears homogeneous by electrophoresis and gel filtration. Its molecular weight is estimated by three different methods to be about 58,000. Its optimal pH is around 8. Protease II activity is unaffected by chelating agents and sulfhydryl reagents. Amidase and proteolytic activities are stimulated by calcium ion, which decreases the enzyme stability. Like pancreatic trypsin, this endopeptidase catalyses the hydrolysis of alpha-amino-substituted lysine and arginine esters. It appears distinct from the previously isolated protease I, which is a chymotrypsin-like enzyme. The apparent Michaelis constant for hydrolysis of N-benzoyl-L-arginine ethyl ester is 4.7 X 10(-4) M. The esterase activity is inhibited by diisopryopylphosphorofluoridate (Ki(app) equals 2.7 X 10(-3) M) and tosyl lysine chloromethyl ketone (Ki(app) equals 1.8 X 10(-5) M), indicating that serine and histidine residues may be present in the active site. However, protease II is insensitive to phenylmethanesulfonyl fluoride and several natural trypsin inhibitors. Its amidase and esterase activities are competitively inhibited by free arginine and aromatic amidines. The proteolytic activity measured on axocasein is very low. In contrast to trypsin, protease II is without effect on native beta-galactosidase. It easily degrades aspartokinase I and III. Nevertheless both enzymes are resistant to proteolysis in the presence of their respective allosteric effectors. These results provide further evidence that such differences in protease susceptibility can be related to the conformational state of the substrate. The possible implication of structural changes in the mechanism of preferential proteolysis in vivo, is discussed."}
{"id": "PMID:240840", "title": "Reversible autophosphorylation of a cyclic 3':5'-AMP-dependent protein kinase from bovine cardiac muscle.", "content": "Purified cyclic adenosine 3':5'-monophosphate (cAMP)-dependent protein kinase of bovine cardiac muscles catalyzes the incorporation of 2 mol of 32P from [gamma-32P]ATP to seryl residues in its cAMP-binding protein. The reaction appears to be catalyzed by the protein kinase itself rather than by a protein kinase kinase and is enhanced by cAMP and by the addition of polyarginine. Phosphorylation of the purified enzyme facilitates its dissociation by cAMP (Erlichman, J., Rosenfeld, R., and Rosen, O.M. (1974) J. Biol. Chem. 249, 5000-5003) but does not affect cAMP binding. At equilibrium, 2 mol of cAMP are bound to both the phospho- and dephospho-enzymes. Phosphorylation of protein kinase is reversible. Upon addition of ADP and Mg2+, phosphate is transferred from the protein to ADP, and ATP is formed. The reverse reaction is optimal at pH 5.5 unlike the forward reaction which has a broad, more alkaline pH activity optimum. It is activated by polyarginine and dependent upon the addition of cAMP to a much greater degree than the forward reaction. The data suggest that the catalytic subunit of protein kinase catalyzes the forward and reverse reactions but do not exclude the possibility that the holoenzyme may also be active. Autophosphorylation by protein kinase and dephosphorylation by phosphrprotein phosphatases of by reverals of the autophosphorylation reaction may regulate the sensitivity of certain protein kinases to activation by cAMP in vivo.", "contents": "Reversible autophosphorylation of a cyclic 3':5'-AMP-dependent protein kinase from bovine cardiac muscle. Purified cyclic adenosine 3':5'-monophosphate (cAMP)-dependent protein kinase of bovine cardiac muscles catalyzes the incorporation of 2 mol of 32P from [gamma-32P]ATP to seryl residues in its cAMP-binding protein. The reaction appears to be catalyzed by the protein kinase itself rather than by a protein kinase kinase and is enhanced by cAMP and by the addition of polyarginine. Phosphorylation of the purified enzyme facilitates its dissociation by cAMP (Erlichman, J., Rosenfeld, R., and Rosen, O.M. (1974) J. Biol. Chem. 249, 5000-5003) but does not affect cAMP binding. At equilibrium, 2 mol of cAMP are bound to both the phospho- and dephospho-enzymes. Phosphorylation of protein kinase is reversible. Upon addition of ADP and Mg2+, phosphate is transferred from the protein to ADP, and ATP is formed. The reverse reaction is optimal at pH 5.5 unlike the forward reaction which has a broad, more alkaline pH activity optimum. It is activated by polyarginine and dependent upon the addition of cAMP to a much greater degree than the forward reaction. The data suggest that the catalytic subunit of protein kinase catalyzes the forward and reverse reactions but do not exclude the possibility that the holoenzyme may also be active. Autophosphorylation by protein kinase and dephosphorylation by phosphrprotein phosphatases of by reverals of the autophosphorylation reaction may regulate the sensitivity of certain protein kinases to activation by cAMP in vivo."}
{"id": "PMID:240841", "title": "Guanylate cyclase from the rat renal medulla. Physical properties and comparison with adenylate cyclase.", "content": "Guanylate cyclase from the rat renal medulla is found in both the soluble and particulate fractions of the cell. Sucrose density gradient centrifugation and gel filtration in H2O and D2O indicate that the enzyme from the soluble cell fraction has the following properties: S20w, 6.3 S; Stokes radius, 54 A; partial specific volume, 0.75 ml/g; mass, 154,000 daltons; f/fo, 1.4; axial ratio (prolate ellipsoid), 7. The addition of 0.1% Lubrol PX to this fraction activates the enzyme and changes thartial specific volume, 0.74 ml/g; mass, 148,000 daltons; f/fo, 1.6; axial ratio (prolate ellipsoid), 11. These findings show that detergent activates the enzyme by changing its conformation and not simply by dispersing nonsedimentable membrane fragments. The dimensions of this guanylate cyclase in detergent are very similar to those of detergent-solubilized adenylate cyclase from the same tissue (Neer, E.J. (1974) J. Biol. Chem. 249, 6527-6531). Guanylate cyclase can be solubilized from the particulate cell fraction with 1% Lubrol PX but has properties quite different from those of the guanylate cyclase in the soluble cell fraction. It is a large aggregate with a value of S20,w of about 10 S, Stokes radius of 65 A, and a mass of approximately 300,000 daltons. However, the peaks of guanylate cyclase activity in column effluents and sucrose density gradients are very broad indicating a mixture of different size proteins. The conditions used to solubilize guanylate cyclase from the particulate fraction also solubilize adenylate cyclase, and the two activities can be separated on the same sucrose gradient. Studies of this sort require a rapid, accurate guanylate cyclase assay. We have developed an assay for guanylate cyclase activity which meets these criteria by adapting the competitive protein binding assay for guanosine cyclic 3':5' monophosphate originally described by Murad et al. (Murad, F., Manganiello, V., and Vaughn, M. (1971) Proc. Natl. Acad. Sci. U.S.A. 68, 736-739).", "contents": "Guanylate cyclase from the rat renal medulla. Physical properties and comparison with adenylate cyclase. Guanylate cyclase from the rat renal medulla is found in both the soluble and particulate fractions of the cell. Sucrose density gradient centrifugation and gel filtration in H2O and D2O indicate that the enzyme from the soluble cell fraction has the following properties: S20w, 6.3 S; Stokes radius, 54 A; partial specific volume, 0.75 ml/g; mass, 154,000 daltons; f/fo, 1.4; axial ratio (prolate ellipsoid), 7. The addition of 0.1% Lubrol PX to this fraction activates the enzyme and changes thartial specific volume, 0.74 ml/g; mass, 148,000 daltons; f/fo, 1.6; axial ratio (prolate ellipsoid), 11. These findings show that detergent activates the enzyme by changing its conformation and not simply by dispersing nonsedimentable membrane fragments. The dimensions of this guanylate cyclase in detergent are very similar to those of detergent-solubilized adenylate cyclase from the same tissue (Neer, E.J. (1974) J. Biol. Chem. 249, 6527-6531). Guanylate cyclase can be solubilized from the particulate cell fraction with 1% Lubrol PX but has properties quite different from those of the guanylate cyclase in the soluble cell fraction. It is a large aggregate with a value of S20,w of about 10 S, Stokes radius of 65 A, and a mass of approximately 300,000 daltons. However, the peaks of guanylate cyclase activity in column effluents and sucrose density gradients are very broad indicating a mixture of different size proteins. The conditions used to solubilize guanylate cyclase from the particulate fraction also solubilize adenylate cyclase, and the two activities can be separated on the same sucrose gradient. Studies of this sort require a rapid, accurate guanylate cyclase assay. We have developed an assay for guanylate cyclase activity which meets these criteria by adapting the competitive protein binding assay for guanosine cyclic 3':5' monophosphate originally described by Murad et al. (Murad, F., Manganiello, V., and Vaughn, M. (1971) Proc. Natl. Acad. Sci. U.S.A. 68, 736-739)."}
{"id": "PMID:240842", "title": "A highly stable adenosine triphosphatase from a thermophillie bacterium. Purification, properties, and reconstitution.", "content": "1. A highly stable ATPase (TF1) was purified to a monodispersed state from the membranes of a thermophilic bacterium PS3. Its molecular weight was 380,000, and it was composed of five subunits alpha, beta, gamma, sigma', and sigma with molecular weights of 56,000, 53,000, 32,000, 15,500, and 11,000, respectively. 2. TF1 was stable against dissociating agents such as 5.5 M urea and 4.0 M LiCl, organic solvents, such as 60% acetone, heavy metals, and detergents. Low concentrations of all these agents stimulated its activity at 60 degrees. 3. TF1 was not cold-labile and showed a maximal activity at 70 degrees. Its CD spectrum revealed that its conformation changed between 81 and 96 degrees, and that its contents of alpha helices and beta structures were 27.3 and 12.8%, respectively, at 75 degrees. 4. TF1 was completely dissociated by treatment with dodecyl sulfate at 60 degrees and then with 7.1 M urea. The dissociated TF1 was reconstituted by treatment with Dowex 1-X2, and then dialysis. 5. [3H]Acetyl-TF1 bound to TF1-depleted membranes. TF1 only catalyzed 32Pi-ATP exchange and showed sensitivity to inhibitors of energy transfer when bound to the membranes. 6. A hydrophobic membrance component (TFo) was isolated which rendered TF1 sensitive to inhibitors of energy transfer. It was composed of three subunits (with molecular weights of 19,000, 13,500, and 5,400) and P-lipids.", "contents": "A highly stable adenosine triphosphatase from a thermophillie bacterium. Purification, properties, and reconstitution. 1. A highly stable ATPase (TF1) was purified to a monodispersed state from the membranes of a thermophilic bacterium PS3. Its molecular weight was 380,000, and it was composed of five subunits alpha, beta, gamma, sigma', and sigma with molecular weights of 56,000, 53,000, 32,000, 15,500, and 11,000, respectively. 2. TF1 was stable against dissociating agents such as 5.5 M urea and 4.0 M LiCl, organic solvents, such as 60% acetone, heavy metals, and detergents. Low concentrations of all these agents stimulated its activity at 60 degrees. 3. TF1 was not cold-labile and showed a maximal activity at 70 degrees. Its CD spectrum revealed that its conformation changed between 81 and 96 degrees, and that its contents of alpha helices and beta structures were 27.3 and 12.8%, respectively, at 75 degrees. 4. TF1 was completely dissociated by treatment with dodecyl sulfate at 60 degrees and then with 7.1 M urea. The dissociated TF1 was reconstituted by treatment with Dowex 1-X2, and then dialysis. 5. [3H]Acetyl-TF1 bound to TF1-depleted membranes. TF1 only catalyzed 32Pi-ATP exchange and showed sensitivity to inhibitors of energy transfer when bound to the membranes. 6. A hydrophobic membrance component (TFo) was isolated which rendered TF1 sensitive to inhibitors of energy transfer. It was composed of three subunits (with molecular weights of 19,000, 13,500, and 5,400) and P-lipids."}
{"id": "PMID:240843", "title": "Purification and properties of a dicyclohexylcarbodiimide-sensitive adenosine triphosphatase from a thermophilic bacterium.", "content": "1. A stable ATPase complex with sensitivity to dicyclohexylcarbodiimide (TFo-F1) was purified from the membranes of the thermophilic aerobic bacterium PS3, by ion exchange chromatography in the presence of Triton X-100. 2. The ATPase of TFo-F1 was maximal at 70 degrees at pH 8.6 and was stable after monomerization in 4 M urea and 0.5% Triton X-100 at 25 degrees. The activity was dependent on Mg2+, Co2+, or Mn2+, and it became insensitive to dicyclohexylcarbodiimide when Ca2+ or Cd2+ was added instead. 3. TFo-F1 required P-lipids of this bacterium contained branched fatty acyl groups but no unsaturated groups and were stable against oxidation and heat. 4. Studies by electron microscopy, gel electrophoresis, and use of anti-ATPase antibody and [3H]acetyl-ATPase indicated that the TFo-F1 complex was composed of an ATPase moiety (TF1, five different subunits) and a hydrophobic moiety (TFo, three different subunits. TFo conferred TF1 with sensitivity to dicyclohexylcarbodiimide. 5. Vesicles catalyzing 32Pi-ATP exchange and ATP-driven enhancement of fluorescence of anilinonaphthalene sulfonate were reconstituted by dialyzing pure TFo-F1 and P-lipids together, and were active even at 50-75 degrees. The vesicles reconstituted from TFo-F1 and bacterial P-lipids were more stable than those reconstituted from TFo-F1 and soybean P-lipids.", "contents": "Purification and properties of a dicyclohexylcarbodiimide-sensitive adenosine triphosphatase from a thermophilic bacterium. 1. A stable ATPase complex with sensitivity to dicyclohexylcarbodiimide (TFo-F1) was purified from the membranes of the thermophilic aerobic bacterium PS3, by ion exchange chromatography in the presence of Triton X-100. 2. The ATPase of TFo-F1 was maximal at 70 degrees at pH 8.6 and was stable after monomerization in 4 M urea and 0.5% Triton X-100 at 25 degrees. The activity was dependent on Mg2+, Co2+, or Mn2+, and it became insensitive to dicyclohexylcarbodiimide when Ca2+ or Cd2+ was added instead. 3. TFo-F1 required P-lipids of this bacterium contained branched fatty acyl groups but no unsaturated groups and were stable against oxidation and heat. 4. Studies by electron microscopy, gel electrophoresis, and use of anti-ATPase antibody and [3H]acetyl-ATPase indicated that the TFo-F1 complex was composed of an ATPase moiety (TF1, five different subunits) and a hydrophobic moiety (TFo, three different subunits. TFo conferred TF1 with sensitivity to dicyclohexylcarbodiimide. 5. Vesicles catalyzing 32Pi-ATP exchange and ATP-driven enhancement of fluorescence of anilinonaphthalene sulfonate were reconstituted by dialyzing pure TFo-F1 and P-lipids together, and were active even at 50-75 degrees. The vesicles reconstituted from TFo-F1 and bacterial P-lipids were more stable than those reconstituted from TFo-F1 and soybean P-lipids."}
{"id": "PMID:240844", "title": "Glucagon stimulation of mitochondrial respiration.", "content": "Acute glucagon treatment of intact rats has been found to cause a stimulation of hepatic mitochondrial respiration as measured by monitoring oxygen uptake polarographically. Rates of State 3 respiration with several NAD-linked substrates and succinate were increased significantly after hormonal treatment and isolation of mitochondria. This stimulation cannot be ascribed to a partial uncoupling effect since State 4 respiration as measured by monitoring oxygen uptake polarographically. Rates of State 3 respiration with either slightly increased or unchanged. Furthermore, rates of uncoupled respiration with these substrates were also stimulated after hormonal treatment. On the other hand, respiratory rates (State 3, 4, and uncoupled) with ascorbate-N,N,N',N'-tetramethyl-p-phenylenediamine as substrate were unaffected by glucagon treatment. The hormonally stimulated rates of respiration produced a corresponding increase in the rate of generation of high energy state as indicated in measurements of Ca2+ uptake by isolated mitochondria. Rates of Ca2+ uptake were monitored by two methods: measurement of initial rates of proton ejection following CaCl2 additions and measurement of disappearance of Ca2+ from the suspension medium using murexide as indicator in a dual wavelength spectrophotometer. A significant stimulation in the initial rate of succinate-dependent Ca2+ uptake was noted after glucagon treatment of animals and isolation of hepatic mitochondria. No effect of the hormonal treatment was seen on the extent of Ca2+ uptake or the stoichiometry of H+ ejected per Ca2+ taken up. That the hormonal effect on Ca2+ transport is at the level of the substrate-induced generation of high energy state is indicated by the observation that no effect of glucagon treatment is seen on ATP-dependent Ca2+ uptake. Glucagon-induced changes in the activities of substrate-metabolizing enzymes are considered unlikely for the following reasons: (a) previously published data showed a lack of a hormonal effect on pyruvate-metabolizing enzymes and (b) data in this study showing no effect of glucagon treatment on the activity of NAD-malate dehydrogenase as measured in mitochondrial lysates. All of these observations are consistent with either an activation of mitochondrial substrate transport and/or a stimulation of mitochondrial electron transport by glucagon treatment. Regardless of the exact mechanism involved, the effect of the hormonal treatment is to produce an increase in ATP synthetic and ion-pumping capability during a period of increased energy demand, i.e. increased gluconeogenesis.", "contents": "Glucagon stimulation of mitochondrial respiration. Acute glucagon treatment of intact rats has been found to cause a stimulation of hepatic mitochondrial respiration as measured by monitoring oxygen uptake polarographically. Rates of State 3 respiration with several NAD-linked substrates and succinate were increased significantly after hormonal treatment and isolation of mitochondria. This stimulation cannot be ascribed to a partial uncoupling effect since State 4 respiration as measured by monitoring oxygen uptake polarographically. Rates of State 3 respiration with either slightly increased or unchanged. Furthermore, rates of uncoupled respiration with these substrates were also stimulated after hormonal treatment. On the other hand, respiratory rates (State 3, 4, and uncoupled) with ascorbate-N,N,N',N'-tetramethyl-p-phenylenediamine as substrate were unaffected by glucagon treatment. The hormonally stimulated rates of respiration produced a corresponding increase in the rate of generation of high energy state as indicated in measurements of Ca2+ uptake by isolated mitochondria. Rates of Ca2+ uptake were monitored by two methods: measurement of initial rates of proton ejection following CaCl2 additions and measurement of disappearance of Ca2+ from the suspension medium using murexide as indicator in a dual wavelength spectrophotometer. A significant stimulation in the initial rate of succinate-dependent Ca2+ uptake was noted after glucagon treatment of animals and isolation of hepatic mitochondria. No effect of the hormonal treatment was seen on the extent of Ca2+ uptake or the stoichiometry of H+ ejected per Ca2+ taken up. That the hormonal effect on Ca2+ transport is at the level of the substrate-induced generation of high energy state is indicated by the observation that no effect of glucagon treatment is seen on ATP-dependent Ca2+ uptake. Glucagon-induced changes in the activities of substrate-metabolizing enzymes are considered unlikely for the following reasons: (a) previously published data showed a lack of a hormonal effect on pyruvate-metabolizing enzymes and (b) data in this study showing no effect of glucagon treatment on the activity of NAD-malate dehydrogenase as measured in mitochondrial lysates. All of these observations are consistent with either an activation of mitochondrial substrate transport and/or a stimulation of mitochondrial electron transport by glucagon treatment. Regardless of the exact mechanism involved, the effect of the hormonal treatment is to produce an increase in ATP synthetic and ion-pumping capability during a period of increased energy demand, i.e. increased gluconeogenesis."}
{"id": "PMID:240845", "title": "Nuclear DNA polymerases and the HeLa cell cycle.", "content": "Purified nuclei of HeLa S3 cells contain two DNA-dependent DNA polymerases that have distinct physical and enzymatic properties. We have investigated the variations in their activity during the cell cycle of a synchronized culture. Cells were synchronized by a double thymidine block, harvested at various phases of the cycle, and the two DNA polymerases were purified partially by DEAE-cellulose and phosphocellulose chromatography. The activity of DNA polymerase I (low molecular weight, N-ethylmaleimide-insensitive) remains essentially constant throughout the cycle. The activity of DNA polymerase II (high molecular weight, N-ethylmaleimide-sensitive), however, increases during G1 to mid-S and declines, 7- to 10-fold between late-S and G2. Addition of cycloheximide (60 mug/ml) to cultures 12 hours after the release from thymidine block abolishes the rise in the activity of DNA polymerase II. Cycloheximide also reduced the activity of DNA polymerase I by 60%. Addition of hydroxyurea (1mM) at 1 hour after release has no effect on the activity of either enzyme. We conclude that in HeLa cells, DNA polymerase I and II are distinct enzymes, that DNA polymerase II probably functions in DNA replication and is probably induced in response to stimuli for DNA biosynthesis.", "contents": "Nuclear DNA polymerases and the HeLa cell cycle. Purified nuclei of HeLa S3 cells contain two DNA-dependent DNA polymerases that have distinct physical and enzymatic properties. We have investigated the variations in their activity during the cell cycle of a synchronized culture. Cells were synchronized by a double thymidine block, harvested at various phases of the cycle, and the two DNA polymerases were purified partially by DEAE-cellulose and phosphocellulose chromatography. The activity of DNA polymerase I (low molecular weight, N-ethylmaleimide-insensitive) remains essentially constant throughout the cycle. The activity of DNA polymerase II (high molecular weight, N-ethylmaleimide-sensitive), however, increases during G1 to mid-S and declines, 7- to 10-fold between late-S and G2. Addition of cycloheximide (60 mug/ml) to cultures 12 hours after the release from thymidine block abolishes the rise in the activity of DNA polymerase II. Cycloheximide also reduced the activity of DNA polymerase I by 60%. Addition of hydroxyurea (1mM) at 1 hour after release has no effect on the activity of either enzyme. We conclude that in HeLa cells, DNA polymerase I and II are distinct enzymes, that DNA polymerase II probably functions in DNA replication and is probably induced in response to stimuli for DNA biosynthesis."}
{"id": "PMID:240846", "title": "Characteristics of a pyrimidine-specific 5'-nucleotidase in human erythrocytes.", "content": "A 5'-nucleotidase with unique specificity has been identified in the soluble fraction of normal human erythrocytes. It mediates the hydrolytic dephosphorylation of pyrimidine 5'-ribosemonophosphates but is catalytically ineffective with purine nucleotides or with the 2'-, 3'-, or cyclic isomers of pyrimidine nucleotides. Activities at 37 degrees in dialyzed hemolysates of nromal human erythrocytes averaged 7.3 and 6.2 mumol of Pi liberated per hour per g of hemoglobin for the substrates UMP and CMP, respectively. Activity with TMP as substrate was approximately one-half as much as with UMP or CMP. Apparent Michaelis constants were 0.33 mM UMP, 0.15 mM CMP, and 1.0 mM TMP. Magnesium was required for optimal activity, and this cation could not be replaced by Mn2+. Maximum activity was obtained between pH 7.0 and 7.5 with rapid decreases in more alkaline media and moderate decreases with acidification. The enzyme was quite sensitive to heat and was strongly inhibited by AMP, by some purine bases, and by both purine and pyrimidine nucleosides. Divalent cations of heavy metals were also strongly inhibitory, as were agents active against sulfhydryl groups. The presence of substrates and/or 2-mercaptoethanol provided considerable protection against some of these deleterious agents and conditions. Pyrimidine 5'-nucleotidase activity in hemolysates was clearly distinguishable from erythrocyte acid phosphatase and from leukocyte and serum alkaline phosphatases and nucleotidases.", "contents": "Characteristics of a pyrimidine-specific 5'-nucleotidase in human erythrocytes. A 5'-nucleotidase with unique specificity has been identified in the soluble fraction of normal human erythrocytes. It mediates the hydrolytic dephosphorylation of pyrimidine 5'-ribosemonophosphates but is catalytically ineffective with purine nucleotides or with the 2'-, 3'-, or cyclic isomers of pyrimidine nucleotides. Activities at 37 degrees in dialyzed hemolysates of nromal human erythrocytes averaged 7.3 and 6.2 mumol of Pi liberated per hour per g of hemoglobin for the substrates UMP and CMP, respectively. Activity with TMP as substrate was approximately one-half as much as with UMP or CMP. Apparent Michaelis constants were 0.33 mM UMP, 0.15 mM CMP, and 1.0 mM TMP. Magnesium was required for optimal activity, and this cation could not be replaced by Mn2+. Maximum activity was obtained between pH 7.0 and 7.5 with rapid decreases in more alkaline media and moderate decreases with acidification. The enzyme was quite sensitive to heat and was strongly inhibited by AMP, by some purine bases, and by both purine and pyrimidine nucleosides. Divalent cations of heavy metals were also strongly inhibitory, as were agents active against sulfhydryl groups. The presence of substrates and/or 2-mercaptoethanol provided considerable protection against some of these deleterious agents and conditions. Pyrimidine 5'-nucleotidase activity in hemolysates was clearly distinguishable from erythrocyte acid phosphatase and from leukocyte and serum alkaline phosphatases and nucleotidases."}
{"id": "PMID:240847", "title": "Subcellular distribution and properties of progesterone (delta4-steroid) 5alpha-reductase in rat medial basal hypothalamus.", "content": "The subcellular distribution and properties of rat hypothalamic progesterone 5 alpha-reductase, which accelerates the conversion of progesterone to 5 alpha-pregnane-3,20-dione, have been investigated by utilizing 3H-labeled substrate and a reverse isotopic dilution assay system. The enxymic activity was associated primarily with a cell debris-membranes fraction deribed from the 100 x g pellet. This fraction contained mainly membrane-like particulates and was free of nuclei. Little or no activity was associated with the purified nuclei. The hypothalamic 5 alpha-reductase was stimulated by NADPH but not by NADH. The reaction proceeded optimally over a pH range of 6.0 to 7.2 and at a temperaturhe substrate specificity of the enzyme for other delta 4-3-ketosteroids and the ability of these steroids to inhibit the 5 alpha reduction of [1,2-3H]progesterone as well as the effect of 17 beta-estradiol were also studied. 20 alpha-hydroxypregn-4-en-3-one was more reactive that progesterone, while testosterone was the least reactive. The estimated Km for 20 alpha-hydroxypregn-4-en-3-one was 8.6 +/- 1.9 x 10(-7) M, and for testosterone, 1.6 +/- 1.4 x 10(-5) M. The inhibition studies indicate that 20 alpha-hydroxypregn-4-en-3-one and 17 beta-estradiol are competitive and noncompetitive inhibitors, respectively, of the 5 alpha reduction of progesterone with Ki of 6.0 +/- 3.0 x 10(-8) M for 20 alpha-hydroxypregn-4-en-3-one and Kii (intercept inhibition constant) of 2.6 +/- 0.7 x 10(-5) M and Kis (slope inhibition constant) of 3.6 +/- 0.6 x 10(-5) M for 17 beta-estradiol. Testosterone is a poor competitive inhibitor of the reaction.", "contents": "Subcellular distribution and properties of progesterone (delta4-steroid) 5alpha-reductase in rat medial basal hypothalamus. The subcellular distribution and properties of rat hypothalamic progesterone 5 alpha-reductase, which accelerates the conversion of progesterone to 5 alpha-pregnane-3,20-dione, have been investigated by utilizing 3H-labeled substrate and a reverse isotopic dilution assay system. The enxymic activity was associated primarily with a cell debris-membranes fraction deribed from the 100 x g pellet. This fraction contained mainly membrane-like particulates and was free of nuclei. Little or no activity was associated with the purified nuclei. The hypothalamic 5 alpha-reductase was stimulated by NADPH but not by NADH. The reaction proceeded optimally over a pH range of 6.0 to 7.2 and at a temperaturhe substrate specificity of the enzyme for other delta 4-3-ketosteroids and the ability of these steroids to inhibit the 5 alpha reduction of [1,2-3H]progesterone as well as the effect of 17 beta-estradiol were also studied. 20 alpha-hydroxypregn-4-en-3-one was more reactive that progesterone, while testosterone was the least reactive. The estimated Km for 20 alpha-hydroxypregn-4-en-3-one was 8.6 +/- 1.9 x 10(-7) M, and for testosterone, 1.6 +/- 1.4 x 10(-5) M. The inhibition studies indicate that 20 alpha-hydroxypregn-4-en-3-one and 17 beta-estradiol are competitive and noncompetitive inhibitors, respectively, of the 5 alpha reduction of progesterone with Ki of 6.0 +/- 3.0 x 10(-8) M for 20 alpha-hydroxypregn-4-en-3-one and Kii (intercept inhibition constant) of 2.6 +/- 0.7 x 10(-5) M and Kis (slope inhibition constant) of 3.6 +/- 0.6 x 10(-5) M for 17 beta-estradiol. Testosterone is a poor competitive inhibitor of the reaction."}
{"id": "PMID:240848", "title": "Activation of guanylate cyclase from rat liver and other tissues by sodium azide.", "content": "Sodium azide, hydroxylamine, and phenylhydrazine at concentrations of 1 mM increased the activity of soluble guanylate cyclase from rat liver 2- to 20-fold. The increased accumulation of guanosine 3':5'-monophosphate in reaction mixtures with sodium azide was not due to altered levels of substrate, GTP, or altered hydrolysis of guanosine 3':5'-monophosphate by cyclic nucleotide phosphodiesterase. The activation of guanylate cyclase was dependent upon NaN3 concentration and temperature; preincubation prevented the time lag of activation observed during incubation. The concentration of NaN3 that resulted in half-maximal activation was 0.04 mM. Sodium azide increased the apparent Km for GTP from 35 to 113 muM. With NaN3 activation the enzyme was less dependent upon the concentration of free Mn2+. Activation of enzyme by NaN3 was irreversible with dilution or dialysis of reaction mixtures. The slopes of Arrhenius plots were altered with sodium azide-activated enzyme, while gel filtration of the enzyme on Sepharose 4B was unaltered by NaN3 treatment. Triton X-100 increased the activity of the enzyme, and in the presence of Triton X-100 the activation by NaN3 was not observed. Trypsin treatment decreased both basal guanylate cyclase activity and the responsiveness to NaN3. Phospholipase A, phospholipase C, and neuraminidase increased basal activity but had little effect on the responsiveness to NaN3. Both soluble and particulate guanylate cyclase from liver and kidney were stimulated with NaN3. The particulate enzyme from cerebral cortex and cerebellum was also activated with NaN3, whereas the soluble enzyme from these tissues was not. Little or no effect of NaN3 was observed with preparations from lung, heart, and several other tissues. The lack of an effect with NaN3 on soluble GUANYLATE Cyclase from heart was probably due to the presence of an inhibitor of NaN3 activation in heart preparations. The effect of NaN3 was decreased or absent when soluble guanylate cyclase from liver was purified or stored at -20degrees. The activation of guanylate cyclase by NaN3 is complex and may be the result of the nucleophilic agent acting on the enzyme directly or what may be more likely on some other factor in liver preparations.", "contents": "Activation of guanylate cyclase from rat liver and other tissues by sodium azide. Sodium azide, hydroxylamine, and phenylhydrazine at concentrations of 1 mM increased the activity of soluble guanylate cyclase from rat liver 2- to 20-fold. The increased accumulation of guanosine 3':5'-monophosphate in reaction mixtures with sodium azide was not due to altered levels of substrate, GTP, or altered hydrolysis of guanosine 3':5'-monophosphate by cyclic nucleotide phosphodiesterase. The activation of guanylate cyclase was dependent upon NaN3 concentration and temperature; preincubation prevented the time lag of activation observed during incubation. The concentration of NaN3 that resulted in half-maximal activation was 0.04 mM. Sodium azide increased the apparent Km for GTP from 35 to 113 muM. With NaN3 activation the enzyme was less dependent upon the concentration of free Mn2+. Activation of enzyme by NaN3 was irreversible with dilution or dialysis of reaction mixtures. The slopes of Arrhenius plots were altered with sodium azide-activated enzyme, while gel filtration of the enzyme on Sepharose 4B was unaltered by NaN3 treatment. Triton X-100 increased the activity of the enzyme, and in the presence of Triton X-100 the activation by NaN3 was not observed. Trypsin treatment decreased both basal guanylate cyclase activity and the responsiveness to NaN3. Phospholipase A, phospholipase C, and neuraminidase increased basal activity but had little effect on the responsiveness to NaN3. Both soluble and particulate guanylate cyclase from liver and kidney were stimulated with NaN3. The particulate enzyme from cerebral cortex and cerebellum was also activated with NaN3, whereas the soluble enzyme from these tissues was not. Little or no effect of NaN3 was observed with preparations from lung, heart, and several other tissues. The lack of an effect with NaN3 on soluble GUANYLATE Cyclase from heart was probably due to the presence of an inhibitor of NaN3 activation in heart preparations. The effect of NaN3 was decreased or absent when soluble guanylate cyclase from liver was purified or stored at -20degrees. The activation of guanylate cyclase by NaN3 is complex and may be the result of the nucleophilic agent acting on the enzyme directly or what may be more likely on some other factor in liver preparations."}
{"id": "PMID:240849", "title": "Purification and properties of phaseolamin, an inhibitor of alpha-amylase, from the kidney bean, Phaseolus vulgaris.", "content": "Kidney beans, Phaseolus vulgaris, contain a proteinaceous inhibitor of alpha-amylase, which we have named phaseolamin. The inhibitor has been purified to homogeneity by conventional protein fractionation methods involving heat treatment, dialysis, and chromatography on DEAE-cellulose, Sephadex G-100, and CM-cellulose. Phaseolamin is specific for animal alpha-amylases, having no activity towards the corresponding plant, bacterial, and fungal enzymes, or any other hydrolytic enzyme tested. Optimal inhibitory activity is expressed during preincubation of enzyme and inhibitor at pH 5.5 and 37 degrees. Substrate prevents inhibition. Measurement of the stoichiometry on inhibition showed that a 1:1 complex of alpha-amylase and inhibitor is formed. Complex formation was demonstrated by chromatography on Sephadex G-100. The phaseolamin-amylase complex is dissociated at low pH values, apparently as a result of destruction of the enzyme; the complex cannot be dissociated by other conditions unfavorable for inhibition (low temperature or high pH). Phaseolamin inhibits hog pancreatic alpha-amylase in a noncompetitive manner.", "contents": "Purification and properties of phaseolamin, an inhibitor of alpha-amylase, from the kidney bean, Phaseolus vulgaris. Kidney beans, Phaseolus vulgaris, contain a proteinaceous inhibitor of alpha-amylase, which we have named phaseolamin. The inhibitor has been purified to homogeneity by conventional protein fractionation methods involving heat treatment, dialysis, and chromatography on DEAE-cellulose, Sephadex G-100, and CM-cellulose. Phaseolamin is specific for animal alpha-amylases, having no activity towards the corresponding plant, bacterial, and fungal enzymes, or any other hydrolytic enzyme tested. Optimal inhibitory activity is expressed during preincubation of enzyme and inhibitor at pH 5.5 and 37 degrees. Substrate prevents inhibition. Measurement of the stoichiometry on inhibition showed that a 1:1 complex of alpha-amylase and inhibitor is formed. Complex formation was demonstrated by chromatography on Sephadex G-100. The phaseolamin-amylase complex is dissociated at low pH values, apparently as a result of destruction of the enzyme; the complex cannot be dissociated by other conditions unfavorable for inhibition (low temperature or high pH). Phaseolamin inhibits hog pancreatic alpha-amylase in a noncompetitive manner."}
{"id": "PMID:240850", "title": "Purification and properties of rabbit liver phosphorylase phosphatase.", "content": "A procedure for the purification of rabbit liver phosphorylase phosphatase is described. The specific activity of the preparation is 2,100 units/mg of protein, representing a 25,000-fold purification. During the initial steps of the purification a large activation of enzyme activity was observed. The molecular weight of the purified enzyme was estimated by Sephadex G-75 chromatography to be 35,000, and by sucrose density ultracentrifugation to be 34,000 (2.9 S). On Na dodecyl-SO4 polyacrylamide disc gel electrophoresis a single component with a molecular weight of 34,000 was observed. The pH optimum is 6.9 to 7.4, and the Km for rabbit muscle phosphorylase alpha is 2 muM. The same procedure is also applicable to the extensive purification of phosphorylase phosphatase from rabbit muscle.", "contents": "Purification and properties of rabbit liver phosphorylase phosphatase. A procedure for the purification of rabbit liver phosphorylase phosphatase is described. The specific activity of the preparation is 2,100 units/mg of protein, representing a 25,000-fold purification. During the initial steps of the purification a large activation of enzyme activity was observed. The molecular weight of the purified enzyme was estimated by Sephadex G-75 chromatography to be 35,000, and by sucrose density ultracentrifugation to be 34,000 (2.9 S). On Na dodecyl-SO4 polyacrylamide disc gel electrophoresis a single component with a molecular weight of 34,000 was observed. The pH optimum is 6.9 to 7.4, and the Km for rabbit muscle phosphorylase alpha is 2 muM. The same procedure is also applicable to the extensive purification of phosphorylase phosphatase from rabbit muscle."}
{"id": "PMID:240851", "title": "Purification, crystallization, and properties of D-ribose isomerase from Mycobacterium smegmatis.", "content": "D-Ribose isomerase, which catalyzes the conversion of D-ribose to D-ribulose, was purified from extracts of Mycobacterium smegmatis grown on D-ribose. The purified enzyme crystalized as hexagonal plates from a 44% solution of ammonium sulfate. The enzyme was homogenous by disc gel electrophoresis and ultracentrifugal analysis. The molecular weight of the enzyme was between 145,000 and 174,000 by sedimentation equilibrium analysis. Its sedimentation constant of 8.7 S indicates it is globular. On the basis of sodium dodecyl sulfate gel electrophoresis in the presence of Mn2+, the enzyme is probably composed of 4 identical subunits of molecular weight about 42,000 to 44,000. The enzyme was specific for sugars having the same configuration as D-ribose at carbon atoms 1 to 3. Thus, the enzyme could also utilize L-lyxose, D-allose, and L-rhamnose as substrates. The Km for D-ribose was 4 mM and for L-lyxose it was 5.3 mM. The enzyme required a divalent cation for activity with optimum activity being shown with Mn2+. the Km for the various cations was as follows: Mn2+, 1 times 10(-7) M, Co2+, 4 times 10(-7) M, and Mg2+, 1.8 times 10(-5) M. The pH optimum for the enzyme was 7.5 to 8.5. Polyols did not inhibit the enzyme to any great extent. The product of the reaction was identified as D-ribulose by thin layer chromatography and by preparation of the O-nitrophenylhydrazone derivative.", "contents": "Purification, crystallization, and properties of D-ribose isomerase from Mycobacterium smegmatis. D-Ribose isomerase, which catalyzes the conversion of D-ribose to D-ribulose, was purified from extracts of Mycobacterium smegmatis grown on D-ribose. The purified enzyme crystalized as hexagonal plates from a 44% solution of ammonium sulfate. The enzyme was homogenous by disc gel electrophoresis and ultracentrifugal analysis. The molecular weight of the enzyme was between 145,000 and 174,000 by sedimentation equilibrium analysis. Its sedimentation constant of 8.7 S indicates it is globular. On the basis of sodium dodecyl sulfate gel electrophoresis in the presence of Mn2+, the enzyme is probably composed of 4 identical subunits of molecular weight about 42,000 to 44,000. The enzyme was specific for sugars having the same configuration as D-ribose at carbon atoms 1 to 3. Thus, the enzyme could also utilize L-lyxose, D-allose, and L-rhamnose as substrates. The Km for D-ribose was 4 mM and for L-lyxose it was 5.3 mM. The enzyme required a divalent cation for activity with optimum activity being shown with Mn2+. the Km for the various cations was as follows: Mn2+, 1 times 10(-7) M, Co2+, 4 times 10(-7) M, and Mg2+, 1.8 times 10(-5) M. The pH optimum for the enzyme was 7.5 to 8.5. Polyols did not inhibit the enzyme to any great extent. The product of the reaction was identified as D-ribulose by thin layer chromatography and by preparation of the O-nitrophenylhydrazone derivative."}
{"id": "PMID:240852", "title": "Characterization of the pyridoxal 5'-phosphate and pyridoxamine 5'-phosphate hydrolase activity in rat liver. Identity with alkaline phosphatase.", "content": "The tissue content of pyridoxal 5'-phosphate is controlled principally by the protein binding of this coenzyme and its hydrolysis by a cellular phosphatase. The present study identifies this enzyme and its intracellular location in rat liver. Pyridoxal-P is not hydrolyzed by the acid phosphatase of intact lysosomes. At pH 7.4 and 9.0, the subcellular distribution of pyridoxal-P phosphatase activity is similar to the for p-nitrophenyl-P, and the major portion of both activities is found in the plasma membrane fraction. The ratio of specific activities for pyridoxal-P and p-nitrophenyl-P hydrolysis remains relatively constant during the isolation of plasma membranes. These activities also behave concordantly with respect to pH rate profile, pH-Km profile, and response to chelating agents, Zn2+, Mg2+, and inhibitors. Kinetic studies indicate that pyridoxal-P binds to same enzyme sites as beta-glycerophosphate and phosphorylcholine. The data strongly favor alkaline phosphatase as the enzyme which functions in the control of pyridoxal-P and pyridoxamine-P metabolism in rat liver. Alkaline phosphatase was solubilized from isolated plasma membranes. The kinetic properties of the enzyme are not markedly altered by its dissociation from the membrane matrix. However, there are significant differences in its behavior toward Mg2+ which suggest a structural role for Mg2+ in liver alkaline phosphatase.", "contents": "Characterization of the pyridoxal 5'-phosphate and pyridoxamine 5'-phosphate hydrolase activity in rat liver. Identity with alkaline phosphatase. The tissue content of pyridoxal 5'-phosphate is controlled principally by the protein binding of this coenzyme and its hydrolysis by a cellular phosphatase. The present study identifies this enzyme and its intracellular location in rat liver. Pyridoxal-P is not hydrolyzed by the acid phosphatase of intact lysosomes. At pH 7.4 and 9.0, the subcellular distribution of pyridoxal-P phosphatase activity is similar to the for p-nitrophenyl-P, and the major portion of both activities is found in the plasma membrane fraction. The ratio of specific activities for pyridoxal-P and p-nitrophenyl-P hydrolysis remains relatively constant during the isolation of plasma membranes. These activities also behave concordantly with respect to pH rate profile, pH-Km profile, and response to chelating agents, Zn2+, Mg2+, and inhibitors. Kinetic studies indicate that pyridoxal-P binds to same enzyme sites as beta-glycerophosphate and phosphorylcholine. The data strongly favor alkaline phosphatase as the enzyme which functions in the control of pyridoxal-P and pyridoxamine-P metabolism in rat liver. Alkaline phosphatase was solubilized from isolated plasma membranes. The kinetic properties of the enzyme are not markedly altered by its dissociation from the membrane matrix. However, there are significant differences in its behavior toward Mg2+ which suggest a structural role for Mg2+ in liver alkaline phosphatase."}
{"id": "PMID:240853", "title": "Nuclear deoxyribonucleic acid polymerases of liver.", "content": "Hepatic nuclei that are isolated in aquenous solutions of low ionic strength or glycerol contain all or nearly all the nonmitochondrial DNA polymerase activity of the cell. The presence of polymerase activity in the cytoplasm is due to extraction of nuclear enzymes by buffer and inorganic salts. Even with low ionic strength solutions, some leaching of nuclear enzymes occurs if the concentration of liver in the homogenizing medium is greater than 10%. As defined by sucrose gradient analysis, the normal adult rat liver nucleus contains mainly or entirely a single species of DNA polymerase (3.2 S) whereas the regenerating nucleus after 70% hepatectomy has an additional enzyme (7.1 S). The total activity of regenerating nuclei is about twice the normal value. The increase resides in the 7.1 S activity. The 7.1 S DNA polymerase had been purified partially from regenerating liver nuclei (isolated in low ionic strength solutions) and cytosol (prepared under conditions of nuclear enzyme extraction). The properties of the activity from the two sources are indistinguishable. A mixture of albumin and spermidine enhances by several-fold the activities of the 3.2 S and 7.1 S DNA polymerases. In the presence of spermidine, but not in its absence, the activity of the 7.1 S DNA polymerase is strictly proportional to the amount of the enzyme preparation.", "contents": "Nuclear deoxyribonucleic acid polymerases of liver. Hepatic nuclei that are isolated in aquenous solutions of low ionic strength or glycerol contain all or nearly all the nonmitochondrial DNA polymerase activity of the cell. The presence of polymerase activity in the cytoplasm is due to extraction of nuclear enzymes by buffer and inorganic salts. Even with low ionic strength solutions, some leaching of nuclear enzymes occurs if the concentration of liver in the homogenizing medium is greater than 10%. As defined by sucrose gradient analysis, the normal adult rat liver nucleus contains mainly or entirely a single species of DNA polymerase (3.2 S) whereas the regenerating nucleus after 70% hepatectomy has an additional enzyme (7.1 S). The total activity of regenerating nuclei is about twice the normal value. The increase resides in the 7.1 S activity. The 7.1 S DNA polymerase had been purified partially from regenerating liver nuclei (isolated in low ionic strength solutions) and cytosol (prepared under conditions of nuclear enzyme extraction). The properties of the activity from the two sources are indistinguishable. A mixture of albumin and spermidine enhances by several-fold the activities of the 3.2 S and 7.1 S DNA polymerases. In the presence of spermidine, but not in its absence, the activity of the 7.1 S DNA polymerase is strictly proportional to the amount of the enzyme preparation."}
{"id": "PMID:240854", "title": "Biosynthesis of cholic acid in rat liver. 24-Hydroxylation of 3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholestanoic acid.", "content": "Conversion of 3alpha, 7alpha, 12alpha-trihydroxy-5beta-[7beta-3H]cholestanoic acid into 3alpha, 7alpha, 12alpha, 24-tetrahydroxy-5beta-cholestanoic acid in rat liver was catalyzed either by the mitochondrial fraction fortified with the 100,000 times g supernatant fluid or the microsomal fraction fortified with 100,000 times g supernatant fluid and ATP. The microsomal system was more active than the mitochondrial system. With the microsomal system the rate of reaction was considerably faster with free 3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholestanoic acid as substrate than with the corresponding coenzyme A ester. Addition of coenzyme A inhibited the activity. Addition of cofactors other than ATP and coenzyme A did not markedly influence the reaction. The 100,000 times g supernatant fluid could be substituted with a protein fraction obtained by ammonium sulfate precipitation and Sephadex chromatography of the 100,000 times g supernatant fluid. The reaction was not catalyzed by a mixed function oxidase since there was no incorporation of 18O into the product when the reaction was performed in an atmosphere containing 18O2. On the other hand, oxygen may be obligatory since there was almost complete inhibition when the reaction was performed in an atmosphere consisting of nitrogen. Carbon monoxide did not inhibit the reaction. One atom of deuterium was incorporated into the product when the reaction was performed in a medium containing deuterated water. It was concluded that microsomal 24-hydroxylation of 3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholestanoic acid involves the combined action of a desaturase and a hydratase. The reaction catalyzed by the hydratase appears to be stereospecific since the 24alpha epimer of 3alpha, 7alpha,12alpha-trihydroxy-5beta-cholestanoic acid was the predominant product. In contrast to the microsomal system, the mitochondrial system was not stimulated by the addition of ATP and was not inhibited by coenzyme A. The coenzyme A ester of 3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholestanoic acid was 24-hydroxylated more efficiently than the free acid.", "contents": "Biosynthesis of cholic acid in rat liver. 24-Hydroxylation of 3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholestanoic acid. Conversion of 3alpha, 7alpha, 12alpha-trihydroxy-5beta-[7beta-3H]cholestanoic acid into 3alpha, 7alpha, 12alpha, 24-tetrahydroxy-5beta-cholestanoic acid in rat liver was catalyzed either by the mitochondrial fraction fortified with the 100,000 times g supernatant fluid or the microsomal fraction fortified with 100,000 times g supernatant fluid and ATP. The microsomal system was more active than the mitochondrial system. With the microsomal system the rate of reaction was considerably faster with free 3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholestanoic acid as substrate than with the corresponding coenzyme A ester. Addition of coenzyme A inhibited the activity. Addition of cofactors other than ATP and coenzyme A did not markedly influence the reaction. The 100,000 times g supernatant fluid could be substituted with a protein fraction obtained by ammonium sulfate precipitation and Sephadex chromatography of the 100,000 times g supernatant fluid. The reaction was not catalyzed by a mixed function oxidase since there was no incorporation of 18O into the product when the reaction was performed in an atmosphere containing 18O2. On the other hand, oxygen may be obligatory since there was almost complete inhibition when the reaction was performed in an atmosphere consisting of nitrogen. Carbon monoxide did not inhibit the reaction. One atom of deuterium was incorporated into the product when the reaction was performed in a medium containing deuterated water. It was concluded that microsomal 24-hydroxylation of 3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholestanoic acid involves the combined action of a desaturase and a hydratase. The reaction catalyzed by the hydratase appears to be stereospecific since the 24alpha epimer of 3alpha, 7alpha,12alpha-trihydroxy-5beta-cholestanoic acid was the predominant product. In contrast to the microsomal system, the mitochondrial system was not stimulated by the addition of ATP and was not inhibited by coenzyme A. The coenzyme A ester of 3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholestanoic acid was 24-hydroxylated more efficiently than the free acid."}
{"id": "PMID:240855", "title": "Self-association of lysozyme. Thermochemical measurements: effect of chemical modification of Trp-62, Trp-108, and Glu-35.", "content": "Heats of dilution and of saccharide binding for hen egg white lysozyme have been measured at 30 degrees, 0.1 ionic strength, and pH 7 over the range 3 to 95 mg of protein/ml. The concentration dependence of the apparent relative molar enthalpy of lysozyme derived from these results gives the thermodynamic parameters for the formation of an intermolecular contact in an indefinite (head-to-tail) self-association process as delta G 0 = -3.9 kcal/mol, delta H 0 = -6.4 kcal/mol, and delta S 0 = -8,3 e.u. Oxindolealanine-62-lysozyme does not undergo self-association reactions that can be detected calorimetrically. This derivative reacts with native lysozyme to form hybrid polymeric species with free energy and enthalpy of interaction similar to those for the polymers of native lysozyme. These results are consistent with the intermolecular contact in the self-assocaition of lysozyme being asymmetric (head-to-tail). The heat of dilution of the derivative of lysozyme in which Glu-35 is blocked as the ester with oxindolealanine-108 is like that observed for native lysozyme in acid solution and is independent of pH. The concentration difference spectrum that develops through self-association is of the shape expected for introduction of an indole chromophore into a charge-free region of the intermolecular contact. The foregoing results indicate that Glu-35 and Trp-62 are part of the contact, that perturbation of Trp-108 does not make a principle contribution to the concentration difference spectrum, and that no acid group other than Glu-35 is perturbed by self-association. There is a small change in the heat of (GlcNAc)3 binding over the range 0.005 to 0.034 M saccharide. These data give the value of -1 kcal/mol for the enthalpy change for formation of the 2:1 saccharide-enzyme complex (ES2) from ES and S.", "contents": "Self-association of lysozyme. Thermochemical measurements: effect of chemical modification of Trp-62, Trp-108, and Glu-35. Heats of dilution and of saccharide binding for hen egg white lysozyme have been measured at 30 degrees, 0.1 ionic strength, and pH 7 over the range 3 to 95 mg of protein/ml. The concentration dependence of the apparent relative molar enthalpy of lysozyme derived from these results gives the thermodynamic parameters for the formation of an intermolecular contact in an indefinite (head-to-tail) self-association process as delta G 0 = -3.9 kcal/mol, delta H 0 = -6.4 kcal/mol, and delta S 0 = -8,3 e.u. Oxindolealanine-62-lysozyme does not undergo self-association reactions that can be detected calorimetrically. This derivative reacts with native lysozyme to form hybrid polymeric species with free energy and enthalpy of interaction similar to those for the polymers of native lysozyme. These results are consistent with the intermolecular contact in the self-assocaition of lysozyme being asymmetric (head-to-tail). The heat of dilution of the derivative of lysozyme in which Glu-35 is blocked as the ester with oxindolealanine-108 is like that observed for native lysozyme in acid solution and is independent of pH. The concentration difference spectrum that develops through self-association is of the shape expected for introduction of an indole chromophore into a charge-free region of the intermolecular contact. The foregoing results indicate that Glu-35 and Trp-62 are part of the contact, that perturbation of Trp-108 does not make a principle contribution to the concentration difference spectrum, and that no acid group other than Glu-35 is perturbed by self-association. There is a small change in the heat of (GlcNAc)3 binding over the range 0.005 to 0.034 M saccharide. These data give the value of -1 kcal/mol for the enthalpy change for formation of the 2:1 saccharide-enzyme complex (ES2) from ES and S."}
{"id": "PMID:240856", "title": "Turkey egg white lysozyme. Free energy, enthalpy, and steady state kinetics of reaction with N-acetylglucosamine oligosaccharides.", "content": "Equilibrium and calorimetric studies of substrate binding to turkey egg white (TEW) lysozyme were carried out at 30degrees as a function of pH (2 to 9) and ligand size (monosaccharide to hexasaccharide of N-acetylglucosamine). Steady state kinetic measurements using the N-acetylglucosamine hexasaccharide were carried out as a function of pH (2 to 9) and temperature (20-60degrees). These experiments allow comparison of the properties of TEW lysozyme with those of the hen egg white (HEW) enzyme reported previously (Banerjee, S. K., Holler, E., Hess, G. P., and Rupley, J. A. (1975) J. Biol. Chem. 250, 4355-4367, and references therein). The free energies and enthalpies of oligosaccharide binding are the same for TEW and HEW lysozymes at pH 2 but are less negative for TEW lysozyme at pH 5. The pH dependence of the binding of (GlcNAc)3 and higher oligomers to TEW lysozyme is like that for the binding of beta-methyl-N-acetylglucosaminide to TEW lysozyme. These data indicate that oligosaccharide ligands bind identically with HEW and TEW lysozymes, except for the interactions of residue 101, which is aspartic acid in the HEW protein and glycine in the TEW protein (Larue, J. N., and Speck, J. C., Jr. (1970) J. Biol. Chem. 245, 1985-1991). The pH dependence of kcat is described by apparent pK values of 3.9 and 6.8 and a maximum value of kcat of 0.135 s-1. A value of 21.0 kcal/mol was calculated for deltaH from the temperature dependence of kcat. These values and the dependence of the transglycosylation reaction on acceptor concentration are within experimental error the same as those for HEW lysozyme. The more acid pK seen in the pH rate profile reflects the ionization of Asp-52 in the lysozyme-(GlcNAc)6 complex. The pK of Asp-52 in the free protein is 0.3 pK unit lower. The essential identity of the active sites of the HEW and TEW enzymes, except for the Asp-101 interactions, allows estimation of the thermodynamic properties associated with formation of the two hydrogen bonds between Asp-101 and substrate as deltaG0 = -1.2 kcal/mol, DeltaH0 = -3.6 kcal/mol, and deltaS0 = -7.9 e.u.", "contents": "Turkey egg white lysozyme. Free energy, enthalpy, and steady state kinetics of reaction with N-acetylglucosamine oligosaccharides. Equilibrium and calorimetric studies of substrate binding to turkey egg white (TEW) lysozyme were carried out at 30degrees as a function of pH (2 to 9) and ligand size (monosaccharide to hexasaccharide of N-acetylglucosamine). Steady state kinetic measurements using the N-acetylglucosamine hexasaccharide were carried out as a function of pH (2 to 9) and temperature (20-60degrees). These experiments allow comparison of the properties of TEW lysozyme with those of the hen egg white (HEW) enzyme reported previously (Banerjee, S. K., Holler, E., Hess, G. P., and Rupley, J. A. (1975) J. Biol. Chem. 250, 4355-4367, and references therein). The free energies and enthalpies of oligosaccharide binding are the same for TEW and HEW lysozymes at pH 2 but are less negative for TEW lysozyme at pH 5. The pH dependence of the binding of (GlcNAc)3 and higher oligomers to TEW lysozyme is like that for the binding of beta-methyl-N-acetylglucosaminide to TEW lysozyme. These data indicate that oligosaccharide ligands bind identically with HEW and TEW lysozymes, except for the interactions of residue 101, which is aspartic acid in the HEW protein and glycine in the TEW protein (Larue, J. N., and Speck, J. C., Jr. (1970) J. Biol. Chem. 245, 1985-1991). The pH dependence of kcat is described by apparent pK values of 3.9 and 6.8 and a maximum value of kcat of 0.135 s-1. A value of 21.0 kcal/mol was calculated for deltaH from the temperature dependence of kcat. These values and the dependence of the transglycosylation reaction on acceptor concentration are within experimental error the same as those for HEW lysozyme. The more acid pK seen in the pH rate profile reflects the ionization of Asp-52 in the lysozyme-(GlcNAc)6 complex. The pK of Asp-52 in the free protein is 0.3 pK unit lower. The essential identity of the active sites of the HEW and TEW enzymes, except for the Asp-101 interactions, allows estimation of the thermodynamic properties associated with formation of the two hydrogen bonds between Asp-101 and substrate as deltaG0 = -1.2 kcal/mol, DeltaH0 = -3.6 kcal/mol, and deltaS0 = -7.9 e.u."}
{"id": "PMID:240857", "title": "Optical properties of lysozyme. pH and saccharide binding difference spectra.", "content": "Difference spectra associated with changes in pH and with binding of saccharides have been recorded for hen egg white (HEW) lysozyme, turkey egg white (TEW) lysozyme, and for the derivatives of the hen protein in which Tre-62 or Trp-108 had been oxidized specifically to oxindolealanine to give the Oxa-62 or Oxa-108-proteins. Identical pH difference spectra were obtained for HEW, TEW, and Oxa-62-lysozymes. Oxidation of Trp-108 is reflected in both the high and low pH (pH 7 versus 5 and pH 2 versus 5) difference spectra. The magnitude of the low pH difference spectrum is enhanced by binding of saccharide for HEW and Oxa-62-lysozymes but not for TEW lysozyme. The shapes and magnitudes of saccharide binding difference spectra are affected by oxidation of residues 62 or 108. These results can be interpreted in terms of the perturbations responsible for the lysozyme difference spectra. The pH 7 versus 5 difference spectrum results from perturbation by Glu-35 of Trp-108 and another tryptophan, probably Trp-63. Perturbation of Trp-108 and one or more other tryptophan residues by several carboxylate groups is responsible for the low pH difference spectra of the unliganded HEW and TEW lysozyme molecules. Perturbation of Trp-108 makes a principal contribution to the saccharide-binding difference spectrum. Perturbation of the Oxa-108 chromophore by ionization of Glu-35 or by saccharide binding produces absorbance changes in the 250 to 265 nm region.", "contents": "Optical properties of lysozyme. pH and saccharide binding difference spectra. Difference spectra associated with changes in pH and with binding of saccharides have been recorded for hen egg white (HEW) lysozyme, turkey egg white (TEW) lysozyme, and for the derivatives of the hen protein in which Tre-62 or Trp-108 had been oxidized specifically to oxindolealanine to give the Oxa-62 or Oxa-108-proteins. Identical pH difference spectra were obtained for HEW, TEW, and Oxa-62-lysozymes. Oxidation of Trp-108 is reflected in both the high and low pH (pH 7 versus 5 and pH 2 versus 5) difference spectra. The magnitude of the low pH difference spectrum is enhanced by binding of saccharide for HEW and Oxa-62-lysozymes but not for TEW lysozyme. The shapes and magnitudes of saccharide binding difference spectra are affected by oxidation of residues 62 or 108. These results can be interpreted in terms of the perturbations responsible for the lysozyme difference spectra. The pH 7 versus 5 difference spectrum results from perturbation by Glu-35 of Trp-108 and another tryptophan, probably Trp-63. Perturbation of Trp-108 and one or more other tryptophan residues by several carboxylate groups is responsible for the low pH difference spectra of the unliganded HEW and TEW lysozyme molecules. Perturbation of Trp-108 makes a principal contribution to the saccharide-binding difference spectrum. Perturbation of the Oxa-108 chromophore by ionization of Glu-35 or by saccharide binding produces absorbance changes in the 250 to 265 nm region."}
{"id": "PMID:240858", "title": "Liver microsomal expoxide hydrase. Solubilization, purification, and characterization.", "content": "Epoxide hydrase was solubilized from liver microsomes of phenobarbital-treated rats by treatment with cholate and purified to apparent homogeneity by ammonium sulfate fractionation and column chromatography in the presence of the nonionic detergent Emulgen 911 on DEAE-cellulose and hydroxylapatite. The purified enzyme preparation had a single major band with a molecular weight of 53,000 to 54,000 on polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Other studies indicated that in the absence of sodium dodecyl sulfate, purified epoxide hydrase exists as high molecular weight aggregates. The preparation was essentially free of heme and flavin, but still contained small amounts of lipids and Emulgen 911.", "contents": "Liver microsomal expoxide hydrase. Solubilization, purification, and characterization. Epoxide hydrase was solubilized from liver microsomes of phenobarbital-treated rats by treatment with cholate and purified to apparent homogeneity by ammonium sulfate fractionation and column chromatography in the presence of the nonionic detergent Emulgen 911 on DEAE-cellulose and hydroxylapatite. The purified enzyme preparation had a single major band with a molecular weight of 53,000 to 54,000 on polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Other studies indicated that in the absence of sodium dodecyl sulfate, purified epoxide hydrase exists as high molecular weight aggregates. The preparation was essentially free of heme and flavin, but still contained small amounts of lipids and Emulgen 911."}
{"id": "PMID:240859", "title": "Evidence for biased bidirectional polymerization of actin filaments using heavy meromyosin prepared by an improved method.", "content": "Isolated actin filaments decorated with HMM can grow by addition of actin monomers to either end, although there is a bias toward addition at the end which is normally attached to the Z line in striated muscle.", "contents": "Evidence for biased bidirectional polymerization of actin filaments using heavy meromyosin prepared by an improved method. Isolated actin filaments decorated with HMM can grow by addition of actin monomers to either end, although there is a bias toward addition at the end which is normally attached to the Z line in striated muscle."}
{"id": "PMID:240860", "title": "Interaction of phospholipid vesicles with cultured mammalial cells. I. Characteristics of uptake.", "content": "The interaction of monolayer cultures of Chinese hamster V79 cells with artificially generated, unilamellar lipid vesicles (approximately 500 A diameter) was examined. Vesicles prepared from a variety of natural and synthetic radiolabeled phosphatidyl cholines (lecithins) were incubated with V79 cells bathed in a simple balanced salt solution. After incubation, the cells were analyzed for exogenous lipid incorporation. Large quantities (approximately 10(8) molecules/cell/h) of lecithin became cell associated without affecting cell viability. The effects of pH, charged lipids, and the influence of the vesicle lipid phase transition on the uptake process were examined. Glutaraldehyde fixation of cells before vesicle treatment, or incubation in the presence of metabolic inhibitors, failed to reduce the lecithin uptake by more than 25-50%, suggesting that the lipid uptake is largely energy independent. Cells in sparse culture took up about ten times more lipid than dense cultures. Prolonged incubation (greater than 15 h) of sparse cell cultures with lecithin vesicles resulted in significant cell death while no deleterious effect was found in dense cultures, or with 1:1 lecithin/cholesterol vesicles. When vesicle-treated cells were homogenized and fractionated, about 20-30% of the exogenous lipid was found in the plasma membrane fraction, with the remainder being distributed into intracellular fractions. Electron microscope radioautography further demonstrated that most of the internalized lipid was present in the cytoplasm, with little in the nucleus. These results are discussed in terms of possible modification of cell behavior by lipid vesicle treatment.", "contents": "Interaction of phospholipid vesicles with cultured mammalial cells. I. Characteristics of uptake. The interaction of monolayer cultures of Chinese hamster V79 cells with artificially generated, unilamellar lipid vesicles (approximately 500 A diameter) was examined. Vesicles prepared from a variety of natural and synthetic radiolabeled phosphatidyl cholines (lecithins) were incubated with V79 cells bathed in a simple balanced salt solution. After incubation, the cells were analyzed for exogenous lipid incorporation. Large quantities (approximately 10(8) molecules/cell/h) of lecithin became cell associated without affecting cell viability. The effects of pH, charged lipids, and the influence of the vesicle lipid phase transition on the uptake process were examined. Glutaraldehyde fixation of cells before vesicle treatment, or incubation in the presence of metabolic inhibitors, failed to reduce the lecithin uptake by more than 25-50%, suggesting that the lipid uptake is largely energy independent. Cells in sparse culture took up about ten times more lipid than dense cultures. Prolonged incubation (greater than 15 h) of sparse cell cultures with lecithin vesicles resulted in significant cell death while no deleterious effect was found in dense cultures, or with 1:1 lecithin/cholesterol vesicles. When vesicle-treated cells were homogenized and fractionated, about 20-30% of the exogenous lipid was found in the plasma membrane fraction, with the remainder being distributed into intracellular fractions. Electron microscope radioautography further demonstrated that most of the internalized lipid was present in the cytoplasm, with little in the nucleus. These results are discussed in terms of possible modification of cell behavior by lipid vesicle treatment."}
{"id": "PMID:240861", "title": "Human platelet myosin. II. In vitro assembly and structure of myosin filaments.", "content": "We have used electron microscopy and solubility measurements to investigate the assembly and structure of purified human platelet myosin and myosin rod into filaments. In buffers with ionic strengths of less than 0.3 M, platelet myosin forms filaments which are remarkable for their small size, being only 320 nm long and 10-11 nm wide in the center of the bare zone. The dimensions of these filaments are not affected greatly by variation of the pH between 7 and 8, variation of the ionic strength between 0.05 and 0.2 M, the presence or absence of 1 mM Mg++ or ATP, or variation of the myosin concentration between 0.05 and 0.7 mg/ml. In 1 mM Ca++ and at pH 6.5 the filaments grow slightly larger. More than 90% of purified platelet myosin molecules assemble into filaments in 0.1 M KC1 at pH 7. Purified preparations of the tail fragment of platelet myosin also form filaments. These filaments are slightly larger than myosin filaments formed under the same conditions, indicating that the size of the myosin filaments may be influenced by some interaction between the head and tail portions of myosin molecules. Calculations based on the size and shape of the myosin filaments, the dimensions of the myosin molecule and analysis of the bare zone reveal that the synthetic platelet myosin filaments consists of 28 myosin molecules arranged in a bipolar array with the heads of two myosin molecules projecting from the backbone of the filament at 14-15 nm intervals. The heads appear to be loosely attached to the backbone by a flexible portion of the myosin tail. Given the concentration of myosin in platelets and the number of myosin molecules per filament, very few of these thin myosin filaments should be present in a thin section of a platelet, even if all of the myosin molecules are aggregated into filaments.", "contents": "Human platelet myosin. II. In vitro assembly and structure of myosin filaments. We have used electron microscopy and solubility measurements to investigate the assembly and structure of purified human platelet myosin and myosin rod into filaments. In buffers with ionic strengths of less than 0.3 M, platelet myosin forms filaments which are remarkable for their small size, being only 320 nm long and 10-11 nm wide in the center of the bare zone. The dimensions of these filaments are not affected greatly by variation of the pH between 7 and 8, variation of the ionic strength between 0.05 and 0.2 M, the presence or absence of 1 mM Mg++ or ATP, or variation of the myosin concentration between 0.05 and 0.7 mg/ml. In 1 mM Ca++ and at pH 6.5 the filaments grow slightly larger. More than 90% of purified platelet myosin molecules assemble into filaments in 0.1 M KC1 at pH 7. Purified preparations of the tail fragment of platelet myosin also form filaments. These filaments are slightly larger than myosin filaments formed under the same conditions, indicating that the size of the myosin filaments may be influenced by some interaction between the head and tail portions of myosin molecules. Calculations based on the size and shape of the myosin filaments, the dimensions of the myosin molecule and analysis of the bare zone reveal that the synthetic platelet myosin filaments consists of 28 myosin molecules arranged in a bipolar array with the heads of two myosin molecules projecting from the backbone of the filament at 14-15 nm intervals. The heads appear to be loosely attached to the backbone by a flexible portion of the myosin tail. Given the concentration of myosin in platelets and the number of myosin molecules per filament, very few of these thin myosin filaments should be present in a thin section of a platelet, even if all of the myosin molecules are aggregated into filaments."}
{"id": "PMID:240862", "title": "The effects of metabolic inhibitors on the synthesis of inducible tyrosine aminotransferase in cultured hepatoma cells.", "content": "The effects of actinomycin-D and 3'-deoxyadenosine (cordycepin) on the steroid-mediated induction of tyrosine aminotransferase (TAT) synthesis have been reexamined in view of recent reports that the primary inhibitory action of these compounds may affect synthesis of proteins as well as RNA. The present results confirm that cordycepin blocks the steroid-mediated induction of TAT in rat hepatoma cells (HTC), but unlike actinomycin-D, cordycepin neither increases nor maintains the levels of TAT found in HTC cells preinduced with dexamethasone. Indeed, cordycepin added to preinduced cells, either in the presence or absence of steroid, causes a prompt decline in TAT activity. These data also confirm that both actinomycin-D and cordycepin have an early inhibitory effect on protein synthesis, but the cordycepin effect is observed sooner and the extent of inhibition is greater. When actinomycin-D and cordycepin are added simultaneously to preinduced cells with the steroid removed, the actinomycin-td produced maintenance of preinduced levels of TAT persists. Also, the inhibition of protein synthesis in cultures with both inhibitors approaches that for the cells treated with actinomycin-D alone instead of cordycepin alone. These data suggest that cordycepin inhibits TAT synthesis in preinduced cells by its inhibition of protein synthesis, and this inhibitory effect of cordycepin is blocked by actinomycin-D. It is possible that actinomycin-D does this by preventing the incorporation of cordycepin into RNA. However, regardless of the correctness of this speculation, the multiple effects of cordycepin indicate that this inhibitor cannot be used either to prove or rule out the post-transcriptional model for regulation of gene expression. Also, this requirement that protein synthesis must continue in order to maintain pre-induced levels of TAT is inconsistent with the assumption that the maintenance of these induced TAT levels by actinomycin-D is due to inhibition of TAT degradation.", "contents": "The effects of metabolic inhibitors on the synthesis of inducible tyrosine aminotransferase in cultured hepatoma cells. The effects of actinomycin-D and 3'-deoxyadenosine (cordycepin) on the steroid-mediated induction of tyrosine aminotransferase (TAT) synthesis have been reexamined in view of recent reports that the primary inhibitory action of these compounds may affect synthesis of proteins as well as RNA. The present results confirm that cordycepin blocks the steroid-mediated induction of TAT in rat hepatoma cells (HTC), but unlike actinomycin-D, cordycepin neither increases nor maintains the levels of TAT found in HTC cells preinduced with dexamethasone. Indeed, cordycepin added to preinduced cells, either in the presence or absence of steroid, causes a prompt decline in TAT activity. These data also confirm that both actinomycin-D and cordycepin have an early inhibitory effect on protein synthesis, but the cordycepin effect is observed sooner and the extent of inhibition is greater. When actinomycin-D and cordycepin are added simultaneously to preinduced cells with the steroid removed, the actinomycin-td produced maintenance of preinduced levels of TAT persists. Also, the inhibition of protein synthesis in cultures with both inhibitors approaches that for the cells treated with actinomycin-D alone instead of cordycepin alone. These data suggest that cordycepin inhibits TAT synthesis in preinduced cells by its inhibition of protein synthesis, and this inhibitory effect of cordycepin is blocked by actinomycin-D. It is possible that actinomycin-D does this by preventing the incorporation of cordycepin into RNA. However, regardless of the correctness of this speculation, the multiple effects of cordycepin indicate that this inhibitor cannot be used either to prove or rule out the post-transcriptional model for regulation of gene expression. Also, this requirement that protein synthesis must continue in order to maintain pre-induced levels of TAT is inconsistent with the assumption that the maintenance of these induced TAT levels by actinomycin-D is due to inhibition of TAT degradation."}
{"id": "PMID:240863", "title": "Early cellular responses to diverse growth stimuli independent of protein and RNA synthesis.", "content": "Serum, elevated pH, excess Zn++, 9,10 dimethyl-1,2 dibenzanthracene (DMBA) and insulin accelerate the progress of growth-inhibited chick embryo cells into the S-period of DNA synthesis. A comparative study was made of their capacity to elicit other cellular responses within two hours after their application. All the agents studied stimulated the uptake of the glucose analogue 2-deoxy-D-glucose (2-dGlc). Elevated pH elicited a more striking increase than the other agents in the uptake of the amino acid analogue alpha-amino isobutyric acid (AIB). The application of subtoxic concentrations of Zn++ or DMBA did not stimulate the uptake of uridine by cells nor its incorporation into RNA when tested at 2 hours. However, it was found that the stimulation of uridine utilization did occur but was delayed several hours. Similarly, the accelerated onset of DNA synthesis was also delayed for several hours by these agents. Insulin acted like serum in stimulating the utilization of 2-dGlc, AIB and uridine. Serum and DMBA were particularly effective in stimulating the utilization of choline. It was concluded that the utilization of 2-dGlc, uridine and thymidine are affected similarly by all the agents, but that there may be differential effects in the utilization of AIB and choline. The inhibition of RNA synthesis by actinomycin D did not prevent the relative stimulation of 2-dGlc, AIB and choline utilization by serum and pH treatment. The inhibition of protein synthesis by cycloheximide did not prevent the relative stimulation of 2-dGlc and choline utilization by serum and pH treatment. It partially blocked the increased uptake of AIB and had erratic effects on the utilization of uridine. It was concluded that neither RNA nor protein synthesis is required for some, if not all, the early responses to growth stimuli measured here. The inhibited cell appears to be a poised system which carries out a programmed array of reactions characteristic of the cell type following perturbation by a variety of unrelated agents. In vivo specificity is provided by the physiological reagents available (i.e., hormones) and their capacity to interact with different cell types.", "contents": "Early cellular responses to diverse growth stimuli independent of protein and RNA synthesis. Serum, elevated pH, excess Zn++, 9,10 dimethyl-1,2 dibenzanthracene (DMBA) and insulin accelerate the progress of growth-inhibited chick embryo cells into the S-period of DNA synthesis. A comparative study was made of their capacity to elicit other cellular responses within two hours after their application. All the agents studied stimulated the uptake of the glucose analogue 2-deoxy-D-glucose (2-dGlc). Elevated pH elicited a more striking increase than the other agents in the uptake of the amino acid analogue alpha-amino isobutyric acid (AIB). The application of subtoxic concentrations of Zn++ or DMBA did not stimulate the uptake of uridine by cells nor its incorporation into RNA when tested at 2 hours. However, it was found that the stimulation of uridine utilization did occur but was delayed several hours. Similarly, the accelerated onset of DNA synthesis was also delayed for several hours by these agents. Insulin acted like serum in stimulating the utilization of 2-dGlc, AIB and uridine. Serum and DMBA were particularly effective in stimulating the utilization of choline. It was concluded that the utilization of 2-dGlc, uridine and thymidine are affected similarly by all the agents, but that there may be differential effects in the utilization of AIB and choline. The inhibition of RNA synthesis by actinomycin D did not prevent the relative stimulation of 2-dGlc, AIB and choline utilization by serum and pH treatment. The inhibition of protein synthesis by cycloheximide did not prevent the relative stimulation of 2-dGlc and choline utilization by serum and pH treatment. It partially blocked the increased uptake of AIB and had erratic effects on the utilization of uridine. It was concluded that neither RNA nor protein synthesis is required for some, if not all, the early responses to growth stimuli measured here. The inhibited cell appears to be a poised system which carries out a programmed array of reactions characteristic of the cell type following perturbation by a variety of unrelated agents. In vivo specificity is provided by the physiological reagents available (i.e., hormones) and their capacity to interact with different cell types."}
{"id": "PMID:240864", "title": "Glutamine synthetase activity in WI-38 cells.", "content": "In the presence of complete growth media (Eagle's MEM), human diploid WI-38 cells have a low level of glutamine synthetase activity. The activity could be increased by depriving the cells of exogenous glutamine; addition of hydrocortisone to either glutamine-deficient or complete medium had no effect on the acitivty of the enzyme. Cell growth ceased under conditions that enhanced glutamine synthetase activity, and hydrocortisone could not reverse this inhibition.", "contents": "Glutamine synthetase activity in WI-38 cells. In the presence of complete growth media (Eagle's MEM), human diploid WI-38 cells have a low level of glutamine synthetase activity. The activity could be increased by depriving the cells of exogenous glutamine; addition of hydrocortisone to either glutamine-deficient or complete medium had no effect on the acitivty of the enzyme. Cell growth ceased under conditions that enhanced glutamine synthetase activity, and hydrocortisone could not reverse this inhibition."}
{"id": "PMID:240865", "title": "Circus movement in dissociated embryonic cells of a teleost, Oryzias latipes.", "content": "The dissociated early embryonic cells of the fresh water fish, Oryzias latipes, protrude hyaline lobopodia, which tend to rotate around the cell circumference in a propagating wave. Cells from late blastula or gastrula continuously show this \"circus movement\", while most cells up to early blastula are rounded. The linear velocity of the lobopodium was estimated by means of time-lapse cinemicrography. The velocity increases slightly as cell diameter increases. The effects of pH, temperature and osmotic pressure of the immersion media on the movement were also quantitatively investigated. Cells become rounded and do not form lobopodial blebs when immersed in media below pH 5. The velocity is reduced by decreasing temperature, but the movement continues even at 5 degrees C. Cells placed in hypertonic salt solutions become crenated and do not continuously demonstrate the circus movement.", "contents": "Circus movement in dissociated embryonic cells of a teleost, Oryzias latipes. The dissociated early embryonic cells of the fresh water fish, Oryzias latipes, protrude hyaline lobopodia, which tend to rotate around the cell circumference in a propagating wave. Cells from late blastula or gastrula continuously show this \"circus movement\", while most cells up to early blastula are rounded. The linear velocity of the lobopodium was estimated by means of time-lapse cinemicrography. The velocity increases slightly as cell diameter increases. The effects of pH, temperature and osmotic pressure of the immersion media on the movement were also quantitatively investigated. Cells become rounded and do not form lobopodial blebs when immersed in media below pH 5. The velocity is reduced by decreasing temperature, but the movement continues even at 5 degrees C. Cells placed in hypertonic salt solutions become crenated and do not continuously demonstrate the circus movement."}
{"id": "PMID:240866", "title": "[Postoperative ileus. Measurement of the changes in intragastric pressure immediately after abdominal operations (practical deductions)].", "content": "During the post-operative period, there is no intestinal paralysis, but simply a transient disorder of motility, the duration and intensity of which are different in the stomach, small intestine and colon. The asynchronism between regularisation of motor activity of the small intestine, which is almost immediate, and that of the colon, which occurs later, is responsible for the clinical picture usually noted. In the light of these new findings, the author analyses the various factors liable to modify the course of post-operative and attempts to suggest appropriate management of the immediate post-operative period.", "contents": "[Postoperative ileus. Measurement of the changes in intragastric pressure immediately after abdominal operations (practical deductions)]. During the post-operative period, there is no intestinal paralysis, but simply a transient disorder of motility, the duration and intensity of which are different in the stomach, small intestine and colon. The asynchronism between regularisation of motor activity of the small intestine, which is almost immediate, and that of the colon, which occurs later, is responsible for the clinical picture usually noted. In the light of these new findings, the author analyses the various factors liable to modify the course of post-operative and attempts to suggest appropriate management of the immediate post-operative period."}
{"id": "PMID:240867", "title": "Progesterone metabolism in normal human endometrium during the menstrual cycle and in endometrial carcinoma.", "content": "Different subcellular fractions (purity checked by electron microscopy and respective marker enzymes) were incubated with 0.1 muCi 14C-progesterone (10 muM) in 0.15 M phosphate buffer at pH 7.4 and 37 C under air for varying periods of time in the presence of NAD(P)H (500 muM). By the preparation of chromic acid oxidation products and acetates, thin-layer chromatography, and crystallisation to constant specific activity, the following metabolites were identified: 20alpha-hydroxypregn-4-en-3-one, 20alpha-hydroxy-5alpha-pregnan-3-one, 20alpha-hydroxy-5beta-pregnan-3-one, 5alpha-pregnane-3,20-dione, and 5beta-pregnane-3,20-dione, indicating the presence of a 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) and 5alpha- and 5beta-reductases. Most of the 20alpha-HSD activity was located in mitochondria (associated mainly with outer membranes) and microsomes. Purified nuclei and cytosol contained 1/6 to 1/18 of the activity of mitochondria and microsomes, respectively. SUBFRACTIONS OF ENDOMETRIAL CELLS ONLY CONTAINED EITHER 5ALPHA- OR 5BETA-REDUCTASE ACTIVITY. 5alpha-reductase activity was mainly associated with microsomes, 5beta-reductase activity was found only in the cytosol. While in normal endometrium specific enzyme activities in subcellular fractions depended on the phase of the cycle, in endometrial carcinoma it depended on the degree of tumour differentiation. The highest values of 5alpha-reductase activity were found in the early proliferative phase. 20alpha-HSD activity was highest in the middle of the secretory phase. The specific activity of the 5alpha-reductase increased with decreasing differentiation of the tumour while the specific activity of the 20alpha-HSD decreased. Kinetic parameters (Km-values, coenzyme requirements and maximum velocities) were determined. The Km-value for progesterone of the 20alpha-HSD in proliferative endometrium was significantly higher than in secretory endometrium, while the Km-values of the 5alpha- and 5beta-reductases were considerably lower during the proliferative than secretory phase.", "contents": "Progesterone metabolism in normal human endometrium during the menstrual cycle and in endometrial carcinoma. Different subcellular fractions (purity checked by electron microscopy and respective marker enzymes) were incubated with 0.1 muCi 14C-progesterone (10 muM) in 0.15 M phosphate buffer at pH 7.4 and 37 C under air for varying periods of time in the presence of NAD(P)H (500 muM). By the preparation of chromic acid oxidation products and acetates, thin-layer chromatography, and crystallisation to constant specific activity, the following metabolites were identified: 20alpha-hydroxypregn-4-en-3-one, 20alpha-hydroxy-5alpha-pregnan-3-one, 20alpha-hydroxy-5beta-pregnan-3-one, 5alpha-pregnane-3,20-dione, and 5beta-pregnane-3,20-dione, indicating the presence of a 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) and 5alpha- and 5beta-reductases. Most of the 20alpha-HSD activity was located in mitochondria (associated mainly with outer membranes) and microsomes. Purified nuclei and cytosol contained 1/6 to 1/18 of the activity of mitochondria and microsomes, respectively. SUBFRACTIONS OF ENDOMETRIAL CELLS ONLY CONTAINED EITHER 5ALPHA- OR 5BETA-REDUCTASE ACTIVITY. 5alpha-reductase activity was mainly associated with microsomes, 5beta-reductase activity was found only in the cytosol. While in normal endometrium specific enzyme activities in subcellular fractions depended on the phase of the cycle, in endometrial carcinoma it depended on the degree of tumour differentiation. The highest values of 5alpha-reductase activity were found in the early proliferative phase. 20alpha-HSD activity was highest in the middle of the secretory phase. The specific activity of the 5alpha-reductase increased with decreasing differentiation of the tumour while the specific activity of the 20alpha-HSD decreased. Kinetic parameters (Km-values, coenzyme requirements and maximum velocities) were determined. The Km-value for progesterone of the 20alpha-HSD in proliferative endometrium was significantly higher than in secretory endometrium, while the Km-values of the 5alpha- and 5beta-reductases were considerably lower during the proliferative than secretory phase."}
{"id": "PMID:240868", "title": "Practical aerobic membrane filtration blood culture technique: development of procedure.", "content": "The advantages of a membrane filter system for blood culturing have been realized for many years. Lysing of the blood prior to filtration is a convenient way to proceed, but previously described lysing procedures result in loss of certain organisms, particularly gram-negative bacilli. Four concentrations of Triton X-100 and sodium carbonate were studied in vitro, and their lysing and antibacterial properties were observed. A solution of 0.08% Na2CO3 and 0.005% Triton X-100 was found to have the least antibacterial effect and gave consistently good lysis and filtration times (under 3 min). An 8.3-ml amount of blood added to 190 ml of this concentration of lysing solution, filtered through three 47-mm membrane filters (0.45-mum pore size), led to recovery of 85% or more of various aerobic and facultative organisms in studies of artificially seeded blood.", "contents": "Practical aerobic membrane filtration blood culture technique: development of procedure. The advantages of a membrane filter system for blood culturing have been realized for many years. Lysing of the blood prior to filtration is a convenient way to proceed, but previously described lysing procedures result in loss of certain organisms, particularly gram-negative bacilli. Four concentrations of Triton X-100 and sodium carbonate were studied in vitro, and their lysing and antibacterial properties were observed. A solution of 0.08% Na2CO3 and 0.005% Triton X-100 was found to have the least antibacterial effect and gave consistently good lysis and filtration times (under 3 min). An 8.3-ml amount of blood added to 190 ml of this concentration of lysing solution, filtered through three 47-mm membrane filters (0.45-mum pore size), led to recovery of 85% or more of various aerobic and facultative organisms in studies of artificially seeded blood."}
{"id": "PMID:240869", "title": "Comparison of recovery rates of various organisms from clinical hypertonic blood cultures by using various concentrations of sodium polyanethol sulfonate.", "content": "By using parallel culture techniques, the recovery rates of a wide spectrum of organisms encountered in hypertonic clinical blood cultures was determined from four different blood culture bottles. Each bottle was identical except for the amount of sodium polyanethol sulfonate (SPS) present. Flasks A, B, C, and D contained SPS in final concentrations of 0.025, 0.05, 0.075, and 0%, respectively. Of 144 patients found to have clinically relevant organisms in their blood cultures, 127 had positive A flasks, 144 had positive B flasks, 140 had positive C flasks, and 110 had positive D flasks. There was no significant difference in the time required to obtain organism recovery from the A, B, or C flasks; however, the time required to obtain organism recovery from the D flask was considerably longer, ranging up to 5 days in many cases. Of the various organisms recovered, 3 of 7 strains of anaerobic streptococci and 1 of 28 strains of Streptococcus pneumoniae appeared to be inhibited by SPS when the concentration was 0.075%. In no case was an organism recovered from either the A or D flask but not from the B flask, indicating that a concentration of 0.05% SPS in hypertonic media does not inhibit the growth of a wide spectrum of organisms in clinical blood cultures.", "contents": "Comparison of recovery rates of various organisms from clinical hypertonic blood cultures by using various concentrations of sodium polyanethol sulfonate. By using parallel culture techniques, the recovery rates of a wide spectrum of organisms encountered in hypertonic clinical blood cultures was determined from four different blood culture bottles. Each bottle was identical except for the amount of sodium polyanethol sulfonate (SPS) present. Flasks A, B, C, and D contained SPS in final concentrations of 0.025, 0.05, 0.075, and 0%, respectively. Of 144 patients found to have clinically relevant organisms in their blood cultures, 127 had positive A flasks, 144 had positive B flasks, 140 had positive C flasks, and 110 had positive D flasks. There was no significant difference in the time required to obtain organism recovery from the A, B, or C flasks; however, the time required to obtain organism recovery from the D flask was considerably longer, ranging up to 5 days in many cases. Of the various organisms recovered, 3 of 7 strains of anaerobic streptococci and 1 of 28 strains of Streptococcus pneumoniae appeared to be inhibited by SPS when the concentration was 0.075%. In no case was an organism recovered from either the A or D flask but not from the B flask, indicating that a concentration of 0.05% SPS in hypertonic media does not inhibit the growth of a wide spectrum of organisms in clinical blood cultures."}
{"id": "PMID:240870", "title": "Survival of anaerobic and aerobic bacteria on cotton swabs in three transport systems.", "content": "The capacity of aerobic and anaerobic bacteria to survive on cotton swabs placed into a dry gassed-out CO2-filled tube (DGT),  dry sterile aerobic tube (DAT), and a tube containing a modified Stuarts' transport medium (MST), was assessed. Pseudomonas aeruginosa increased in numbers by 2 and 3 logs when stored in MST and DAT, respectively. The viability of P. aeruginosa, although retarded when compared to MSA and DAT, was not adversely affected by the CO2 environment in the DGT. The MST maintained relatively constant numbers of Streptococcus pyogenes during the 48-h storage period. The DAT and the DGT were unable to maintain the viability of S. pyogenes. Staphylococcus aureus, when stored in a DGT, DAT, or MST, was maintained in relatively constant numbers throughout the entire storage period. Of the four anaerobic bacteria evaluated (Bacteroides fragilis ssp. thetaiotaomicron, Bacteroides melaninogenicus ssp. asaccharolyticus, Fusobacterium nucleatum, and Peptostreptococcus anaerobius), only B. fragilis ssp. thetaiotamicron survived the 48-h storage period in the DGT. Under these test conditions the DGT did not adequately maintain the viability of the majority of anaerobic bacteria tested (when held on cotton swabs). However, the MST did maintain the viability of all species tested for at least the first 2 h of storage.", "contents": "Survival of anaerobic and aerobic bacteria on cotton swabs in three transport systems. The capacity of aerobic and anaerobic bacteria to survive on cotton swabs placed into a dry gassed-out CO2-filled tube (DGT),  dry sterile aerobic tube (DAT), and a tube containing a modified Stuarts' transport medium (MST), was assessed. Pseudomonas aeruginosa increased in numbers by 2 and 3 logs when stored in MST and DAT, respectively. The viability of P. aeruginosa, although retarded when compared to MSA and DAT, was not adversely affected by the CO2 environment in the DGT. The MST maintained relatively constant numbers of Streptococcus pyogenes during the 48-h storage period. The DAT and the DGT were unable to maintain the viability of S. pyogenes. Staphylococcus aureus, when stored in a DGT, DAT, or MST, was maintained in relatively constant numbers throughout the entire storage period. Of the four anaerobic bacteria evaluated (Bacteroides fragilis ssp. thetaiotaomicron, Bacteroides melaninogenicus ssp. asaccharolyticus, Fusobacterium nucleatum, and Peptostreptococcus anaerobius), only B. fragilis ssp. thetaiotamicron survived the 48-h storage period in the DGT. Under these test conditions the DGT did not adequately maintain the viability of the majority of anaerobic bacteria tested (when held on cotton swabs). However, the MST did maintain the viability of all species tested for at least the first 2 h of storage."}
{"id": "PMID:240871", "title": "Application of counterimmunoelectrophoresis in the identification of Streptococcus pneumoniae in clinical isolates.", "content": "The use of counterimmunoelectrophoresis (CIE) as a diagnostic tool in infectious diseases is becoming more widespread. This study was undertaken to determine the possible use of CIE in the more rapid identification of Streptococcus pneumoniae in clinical isolates. Typing sera were obtained from the Statens Seruminstitut, Denmark. Sixty-seven out of 68 pneumococcal isolates that were optochin sensitive and bile soluble were typed by CIE. One isolate was nontypable even after mouse passage. An additional three isolates that were optochin resistant were considered to be pneumococci on the basis of the bile solubility test and their typability by CIE. Seventy-seven alpha-streptococci were tested for the presence of cross-reacting capsular antigens. Fifty-three alpha-streptococci showed no cross-reactions using the omniserum. Precipitin bands were obtained with the omniserum with 10 of the isolates, but these did not react with type-specific antisera. However, 14 isolates did react with the type-specific pneumococcal antisera. The sensitivity of the test was increased by sonicating whole-cell suspensions before electrophoresis was carried out. Mueller-Hinton broths were inoculated with presumptive pneumococcal colonies that formed the predominant or only colony type on primary blood agar plates. These cultures required a 4-h incubation period with an initial inoculum of 10(6) viable organisms/ml before a precipitin band could be detected. Precipitin bands were observed in 54 out of 56 (97%) broth cultures of pneumococci that had been incubated for 4 h at 37 C. These data suggest that CIE could be a useful tool in the identification of S. pneumoniae isolated from clinical specimens.", "contents": "Application of counterimmunoelectrophoresis in the identification of Streptococcus pneumoniae in clinical isolates. The use of counterimmunoelectrophoresis (CIE) as a diagnostic tool in infectious diseases is becoming more widespread. This study was undertaken to determine the possible use of CIE in the more rapid identification of Streptococcus pneumoniae in clinical isolates. Typing sera were obtained from the Statens Seruminstitut, Denmark. Sixty-seven out of 68 pneumococcal isolates that were optochin sensitive and bile soluble were typed by CIE. One isolate was nontypable even after mouse passage. An additional three isolates that were optochin resistant were considered to be pneumococci on the basis of the bile solubility test and their typability by CIE. Seventy-seven alpha-streptococci were tested for the presence of cross-reacting capsular antigens. Fifty-three alpha-streptococci showed no cross-reactions using the omniserum. Precipitin bands were obtained with the omniserum with 10 of the isolates, but these did not react with type-specific antisera. However, 14 isolates did react with the type-specific pneumococcal antisera. The sensitivity of the test was increased by sonicating whole-cell suspensions before electrophoresis was carried out. Mueller-Hinton broths were inoculated with presumptive pneumococcal colonies that formed the predominant or only colony type on primary blood agar plates. These cultures required a 4-h incubation period with an initial inoculum of 10(6) viable organisms/ml before a precipitin band could be detected. Precipitin bands were observed in 54 out of 56 (97%) broth cultures of pneumococci that had been incubated for 4 h at 37 C. These data suggest that CIE could be a useful tool in the identification of S. pneumoniae isolated from clinical specimens."}
{"id": "PMID:240872", "title": "Dopaminergic neurons in the nematode Caenorhabditis elegans.", "content": "Dopamine is the putative transmitter of eight neurons in the hermaphrodite form of the nematode Caenorhabditis elegans. These include the cephalic and deirid neurons, which are believed to be mechanosensory. The male has an additional six dopaminergic neurons in the tail. Mutants have been selected which have defects in the formaldehyde induced fluorescence and lack dopamine to varying degrees, but they are not insensitive to touch. The dopaminergic neurons of C. elegans are compared with the homologous neurons in Ascaris lumbricoides.", "contents": "Dopaminergic neurons in the nematode Caenorhabditis elegans. Dopamine is the putative transmitter of eight neurons in the hermaphrodite form of the nematode Caenorhabditis elegans. These include the cephalic and deirid neurons, which are believed to be mechanosensory. The male has an additional six dopaminergic neurons in the tail. Mutants have been selected which have defects in the formaldehyde induced fluorescence and lack dopamine to varying degrees, but they are not insensitive to touch. The dopaminergic neurons of C. elegans are compared with the homologous neurons in Ascaris lumbricoides."}
{"id": "PMID:240873", "title": "Ontogeny of monoamine neurons in the locus coeruleus, raphe nuclei and substantia nigra of the rat. II. Synaptogenesis.", "content": "Synaptogenesis was studied in the monoamine (MA) cell groups locus coeruleus (LC), dorsal and medial raphe nuclei (RN) and substantia nigra, zona compacta (SN) between day 18 of gestation and postnatal day 60 using ethanolic phosphotungstic acid (E-PTA) to visualize synaptic profiles. Nuclear area, and cellular packing density (inversely proportional to area of neuropil) were also determined. As determined using the E-PTA method, synaptogenesis begins in the neuropil of the SN first, on or before 18 days of gestation, and in the LC and RN at 19 days. Synaptogenesis on MA cell perikarya is first observed in the SN, on or before 18 days, and in the LC and RN at 20 days. The onset of somatic synaptogenesis coincides with the beginning of nuclear growth and development of the neuropil (decrease in cellular packing density) in all MA cell areas, raising the possibility of common factors in the initiation of these processes. Nonsynaptic contacts precede the appearance of synaptic profiles both in the neuropil and on the somata of the MA cells of the LC, RN and SN, and may represent precursors of mature synapses or desmosome-like contacts. Somatosomatic nonsynaptic contacts occur only prenatally between adjacent MA neurons in the LC, RN and SN. Although some synaptogenesis occurs prenatally in these MA cell groups (indiciating that these parts of the MA circuitry may be functional before birth), most of this synaptogenesis occurs postnatally and continues into adulthood. Since such synaptogenesis does not begin until 2-4 days prior to birth, whereas these neurons and their processes exhibit MA fluorescence as early as 12-14 days of gestation, they apparently are capable of synthesizing transmitter and proliferating terminals before they themselves are innervated.", "contents": "Ontogeny of monoamine neurons in the locus coeruleus, raphe nuclei and substantia nigra of the rat. II. Synaptogenesis. Synaptogenesis was studied in the monoamine (MA) cell groups locus coeruleus (LC), dorsal and medial raphe nuclei (RN) and substantia nigra, zona compacta (SN) between day 18 of gestation and postnatal day 60 using ethanolic phosphotungstic acid (E-PTA) to visualize synaptic profiles. Nuclear area, and cellular packing density (inversely proportional to area of neuropil) were also determined. As determined using the E-PTA method, synaptogenesis begins in the neuropil of the SN first, on or before 18 days of gestation, and in the LC and RN at 19 days. Synaptogenesis on MA cell perikarya is first observed in the SN, on or before 18 days, and in the LC and RN at 20 days. The onset of somatic synaptogenesis coincides with the beginning of nuclear growth and development of the neuropil (decrease in cellular packing density) in all MA cell areas, raising the possibility of common factors in the initiation of these processes. Nonsynaptic contacts precede the appearance of synaptic profiles both in the neuropil and on the somata of the MA cells of the LC, RN and SN, and may represent precursors of mature synapses or desmosome-like contacts. Somatosomatic nonsynaptic contacts occur only prenatally between adjacent MA neurons in the LC, RN and SN. Although some synaptogenesis occurs prenatally in these MA cell groups (indiciating that these parts of the MA circuitry may be functional before birth), most of this synaptogenesis occurs postnatally and continues into adulthood. Since such synaptogenesis does not begin until 2-4 days prior to birth, whereas these neurons and their processes exhibit MA fluorescence as early as 12-14 days of gestation, they apparently are capable of synthesizing transmitter and proliferating terminals before they themselves are innervated."}
{"id": "PMID:240874", "title": "Tonic immobility in chickens: possible involvement of monoamines.", "content": "Tonic immobility in chickens was affected by a variety of drugs that act on monoaminergic systems. Compounds that enhanced the duration of tonic immobility were d-LSD, BOL-148, pargyline, and iproniazid; 5-hydroxytryptophan, p-CPA, and atropine had no effect. Injections of serotonin depressed response duration. A suggestive parallel was noted between the results of the present study and those of previous work reporting drug-induced suppression of raphe electrical activity. The data appear to implicate monoamines, especially serotonin, in the mediation of behavioral activation and suppression.", "contents": "Tonic immobility in chickens: possible involvement of monoamines. Tonic immobility in chickens was affected by a variety of drugs that act on monoaminergic systems. Compounds that enhanced the duration of tonic immobility were d-LSD, BOL-148, pargyline, and iproniazid; 5-hydroxytryptophan, p-CPA, and atropine had no effect. Injections of serotonin depressed response duration. A suggestive parallel was noted between the results of the present study and those of previous work reporting drug-induced suppression of raphe electrical activity. The data appear to implicate monoamines, especially serotonin, in the mediation of behavioral activation and suppression."}
{"id": "PMID:240875", "title": "Effect of age of habit on susceptibility to cycloheximide-induced amnesia in mice.", "content": "The amnesic effects of cycloheximide (CYC) on habits of different ages were investigated in a food-motivated, discrimination-reversal task. Groups of C57BL/6J mice were injected 30 min before training or immediately, 3 days, 6 days, or 9 days after training. Retention was tested 24 hr after CYC treatment. The usual amnesic effect of CYC occurred in animals injected before training. No amnesia was apparent in groups injected immediately, 3 days, or 9 days after training. However, a reliable and reproducible amnesia occurred in the group injected 6 days after training. This amnesia could be reversed by pretest treatment with a monoamine oxidase inhibitor, pheniprazine. Pheniprazine, given 7 days after training, also enhanced retrieval of memory in saline-injected mice.", "contents": "Effect of age of habit on susceptibility to cycloheximide-induced amnesia in mice. The amnesic effects of cycloheximide (CYC) on habits of different ages were investigated in a food-motivated, discrimination-reversal task. Groups of C57BL/6J mice were injected 30 min before training or immediately, 3 days, 6 days, or 9 days after training. Retention was tested 24 hr after CYC treatment. The usual amnesic effect of CYC occurred in animals injected before training. No amnesia was apparent in groups injected immediately, 3 days, or 9 days after training. However, a reliable and reproducible amnesia occurred in the group injected 6 days after training. This amnesia could be reversed by pretest treatment with a monoamine oxidase inhibitor, pheniprazine. Pheniprazine, given 7 days after training, also enhanced retrieval of memory in saline-injected mice."}
{"id": "PMID:240876", "title": "Selective autonomic blockade of conditioned and unconditioned cardiovascular changes in  rhesus monkeys (Macaca mulatta).", "content": "Changes in heart rate and in systolic and diastolic blood pressures were examined in eight rhesus monkeys during six sessions of differential classical conditioning. The conditioned stimuli consisted of tones differing in frequency and the unconditioned stimuli consisted of tail shock. Both the conditioned responses (CRS) and unconditioned responses (UCRs) consisted of increases in heart rate and in systolic and diastolic pressures, but blood pressure CRs sometimes occurred in the absence of heart rate CRs. Graded doses of the selective blocking agents propranolol, phentolamine, and atropine methylnitrate were systemically administered to four of the monkeys prior to additional conditioning sessions. The results suggested that the CRs and UCRs were mediated by both sympathetic and parasympathetic influences.", "contents": "Selective autonomic blockade of conditioned and unconditioned cardiovascular changes in  rhesus monkeys (Macaca mulatta). Changes in heart rate and in systolic and diastolic blood pressures were examined in eight rhesus monkeys during six sessions of differential classical conditioning. The conditioned stimuli consisted of tones differing in frequency and the unconditioned stimuli consisted of tail shock. Both the conditioned responses (CRS) and unconditioned responses (UCRs) consisted of increases in heart rate and in systolic and diastolic pressures, but blood pressure CRs sometimes occurred in the absence of heart rate CRs. Graded doses of the selective blocking agents propranolol, phentolamine, and atropine methylnitrate were systemically administered to four of the monkeys prior to additional conditioning sessions. The results suggested that the CRs and UCRs were mediated by both sympathetic and parasympathetic influences."}
{"id": "PMID:240877", "title": "Neglect and abuse of children: historical aspects, identification, and management.", "content": "The dentist's role primarily involves awareness of the problem of maltreatment, a method of approach to identify and report suspected cases, the documentation of the injuries or neglect which have been observed, and follow-up of any orofacial injuries. Orofacial trauma is present in up to one half of the reported cases of child abuse and consists of bruises, burns, lacerations, and fractures of teeth and jaws. Further studies in the dental field are needed to delineate the types and incidences of orofacial injuries and their relationship to child abuse. Dentists and all professionals must work together, if adequate services are to be provided to protect children and rehabilitate families.", "contents": "Neglect and abuse of children: historical aspects, identification, and management. The dentist's role primarily involves awareness of the problem of maltreatment, a method of approach to identify and report suspected cases, the documentation of the injuries or neglect which have been observed, and follow-up of any orofacial injuries. Orofacial trauma is present in up to one half of the reported cases of child abuse and consists of bruises, burns, lacerations, and fractures of teeth and jaws. Further studies in the dental field are needed to delineate the types and incidences of orofacial injuries and their relationship to child abuse. Dentists and all professionals must work together, if adequate services are to be provided to protect children and rehabilitate families."}
{"id": "PMID:240882", "title": "Nicotinamide adenine dinucleotide phosphate-converting enzymes and adenosine triphosphate citrate lyase in some tissues and organs of New Zealand obese mice with special reference to the enzyme pattern of the pancreatic islets.", "content": "In order to obtain a quantitative estimate of the capacity of the pancreatic islets for provision of cytoplasmic acetyl-coenzyme A and for the turnover of nicotinamide adenine dinucleotide phosphate and its reduced form (NADP+/NADPH), the following enzymes were assayed in islets taken from New Zealand Obese mice: adenosine triphosphate citrate lyase (EC 4.1.3.8), malate dehydrogenase (decarboxylating) (NADP+) (EC 1.1.1.40), glutathione reductase (EC 1.6.4.2) and isocitrate dehydrogenase (NADP+) (EC 1.1.1.42). In addition, the activity of isocitrate dehydrogenase (NAD+) (EC 1.1.1.41) was determined. For comparative purposes the activities in exocrine pancreas, liver, heart muscle, kidney cortex and skeletal muscle were also determined. Specimens of pancreatic islets and the other tissues were microdissected from freeze-dried sections. In comparison with the other tissues, adenosine triphosphate citrate lyase was particularly active in the islets. The NADP+/NAPH-converting enzymes had activities, which suggested a rapid turnover of the islet NADP+/NADPH pool.", "contents": "Nicotinamide adenine dinucleotide phosphate-converting enzymes and adenosine triphosphate citrate lyase in some tissues and organs of New Zealand obese mice with special reference to the enzyme pattern of the pancreatic islets. In order to obtain a quantitative estimate of the capacity of the pancreatic islets for provision of cytoplasmic acetyl-coenzyme A and for the turnover of nicotinamide adenine dinucleotide phosphate and its reduced form (NADP+/NADPH), the following enzymes were assayed in islets taken from New Zealand Obese mice: adenosine triphosphate citrate lyase (EC 4.1.3.8), malate dehydrogenase (decarboxylating) (NADP+) (EC 1.1.1.40), glutathione reductase (EC 1.6.4.2) and isocitrate dehydrogenase (NADP+) (EC 1.1.1.42). In addition, the activity of isocitrate dehydrogenase (NAD+) (EC 1.1.1.41) was determined. For comparative purposes the activities in exocrine pancreas, liver, heart muscle, kidney cortex and skeletal muscle were also determined. Specimens of pancreatic islets and the other tissues were microdissected from freeze-dried sections. In comparison with the other tissues, adenosine triphosphate citrate lyase was particularly active in the islets. The NADP+/NAPH-converting enzymes had activities, which suggested a rapid turnover of the islet NADP+/NADPH pool."}
{"id": "PMID:240883", "title": "Analysis of an HL-A antiserum by iso-electric focusing.", "content": "An anti-HL-A 3 antiserum with cross-reacting activity for HL-A 1 and HL-A 11 was subjected to isoelectric focusing over a pH 5-8 gradient. The cytotoxic activity of the serum focused into three distinct peaks, one at the basic end of the gradient, one between pH 6 and pH 7 and one at the acidic end. The first and second peaks reacted with HL-A 3 positive cells and HL-A 3 negative cells positive for cross-reacting antigens. The third peak reacted only with HL-A 3 positive cells.", "contents": "Analysis of an HL-A antiserum by iso-electric focusing. An anti-HL-A 3 antiserum with cross-reacting activity for HL-A 1 and HL-A 11 was subjected to isoelectric focusing over a pH 5-8 gradient. The cytotoxic activity of the serum focused into three distinct peaks, one at the basic end of the gradient, one between pH 6 and pH 7 and one at the acidic end. The first and second peaks reacted with HL-A 3 positive cells and HL-A 3 negative cells positive for cross-reacting antigens. The third peak reacted only with HL-A 3 positive cells."}
{"id": "PMID:240884", "title": "Interaction of C3b, B, and D in the alternative pathway of complement activation.", "content": "The interaction of ZXd2, an insoluble intermediate of the alternative pathway on zymosan (Z5), with factor B and the enzyme D proceeds in a two-step reaction: 1) B binds in the presence of Mg++ to ZXd2 to form the intermediate ZXd2B, 2) B bound to ZXd2 is subsequently activated enzymatically by D to yield the complex ZXd2B which cleaves C3. Evidence was obtained that C3b, which is present on ZXd2, is required for ZXd2B formation. Studies of the functional role of C3b for ZXd2B formation revealed that C3b is involved in the first reaction step i.e., binding of B to ZXd2 to yield ZXd2B. Formation of ZXd2B is inhibited by pretreatment of ZXd2 with either anti-C3 Fab or with C3b-INA. Low ionic strength of about 2 mS was found to favor the interaction of the C3b with B. Mg++ concentrations from 1 to 31 mM as well as variation of pH in the range from 6.2 to 8.5 did not greatly influence the reaction of B with ZXd2. For the enzymatic activation of B only C3b on ZXd2 and factor D are required. This is concluded from the finding that fluid phase C3b is sufficient for the activation of B in the presence of D. This does not exclude the fact that other proteins present on ZXd2 may help to stabilize the intermediate ZXd2B or the enzymatically active complex AXd2B, or both of them.", "contents": "Interaction of C3b, B, and D in the alternative pathway of complement activation. The interaction of ZXd2, an insoluble intermediate of the alternative pathway on zymosan (Z5), with factor B and the enzyme D proceeds in a two-step reaction: 1) B binds in the presence of Mg++ to ZXd2 to form the intermediate ZXd2B, 2) B bound to ZXd2 is subsequently activated enzymatically by D to yield the complex ZXd2B which cleaves C3. Evidence was obtained that C3b, which is present on ZXd2, is required for ZXd2B formation. Studies of the functional role of C3b for ZXd2B formation revealed that C3b is involved in the first reaction step i.e., binding of B to ZXd2 to yield ZXd2B. Formation of ZXd2B is inhibited by pretreatment of ZXd2 with either anti-C3 Fab or with C3b-INA. Low ionic strength of about 2 mS was found to favor the interaction of the C3b with B. Mg++ concentrations from 1 to 31 mM as well as variation of pH in the range from 6.2 to 8.5 did not greatly influence the reaction of B with ZXd2. For the enzymatic activation of B only C3b on ZXd2 and factor D are required. This is concluded from the finding that fluid phase C3b is sufficient for the activation of B in the presence of D. This does not exclude the fact that other proteins present on ZXd2 may help to stabilize the intermediate ZXd2B or the enzymatically active complex AXd2B, or both of them."}
{"id": "PMID:240885", "title": "The influence of foster nursing on the survival and immunologic competence of mice and rats.", "content": "A series of experiments were undertaken in mice and rats to confirm the report that foster nursing rats of one strain, on mothers of a different strain, can influence their survival and immunologic competence as a consequence of their receiving a significant number of immunologically competent leukocytes via the milk. These experiments have included foster nursing mice and rats, either immediately after birth, or when 25 to 36 hr old, on H-2 incompatible and Ag-B compatible and incompatible mothers, respectively, and challenging them with ear skin grafts of the same genotype as their surrogate mother. They also have included fostering animals rendered tolerant of their surrogate mother's transplantation antigens. In no instance was any evidence obtained that foster nursing can prejudice the survival or influence the immunologic competence of mice or rats.", "contents": "The influence of foster nursing on the survival and immunologic competence of mice and rats. A series of experiments were undertaken in mice and rats to confirm the report that foster nursing rats of one strain, on mothers of a different strain, can influence their survival and immunologic competence as a consequence of their receiving a significant number of immunologically competent leukocytes via the milk. These experiments have included foster nursing mice and rats, either immediately after birth, or when 25 to 36 hr old, on H-2 incompatible and Ag-B compatible and incompatible mothers, respectively, and challenging them with ear skin grafts of the same genotype as their surrogate mother. They also have included fostering animals rendered tolerant of their surrogate mother's transplantation antigens. In no instance was any evidence obtained that foster nursing can prejudice the survival or influence the immunologic competence of mice or rats."}
{"id": "PMID:240886", "title": "Specific partial depletion of graft-vs-host activity by incubation and centrifugation of mouse spleen cells on allogeneic spleen cell monolayers.", "content": "Spleen cells (from BALB/c mice immunized with the C57BL/6 lymphoma EL4, or from non-immune BALB/c) were incubated on monolayers of [C57BL/6 times BALB/cF1 (B6CF1) spleen cells on polylysine-coated polystyrene Petri plate, for 1/2 hr or for 1 hr at 37 degrees C followed by centrifugation of the monolayers for 5 min at 70 times G to 110 times G at 34 to 37 degrees C. Control monolayers were BALB/c spleen cells. As measured by the Simonsen spleen weight assay in neonatal mice, graft-vs-host (GVH) activity was partially depleted in cell populations nonadherent to B6CF1 monolayers. Residual GVH activity of these nonadherent cells was about half that of cells incubated on the control syngeneic monolayers (the mean of eight experiments was 49% +/- 11% S.D.). Two or three consecutive cycles of incubation and centrifugation did not significantly diminish the residual GVH activity, suggesting that spleen cells with GVH activity are heterogeneous with respect to binding to allogeneic target cells under the above conditions. Cell populations nonadherent to third-part [A times AL]F1 monolayers retained full activity, and cell populations partially depleted of GVH activity in B6CF1 neonates had full activity in third-party [BALB/c times AL]F1 neonates.", "contents": "Specific partial depletion of graft-vs-host activity by incubation and centrifugation of mouse spleen cells on allogeneic spleen cell monolayers. Spleen cells (from BALB/c mice immunized with the C57BL/6 lymphoma EL4, or from non-immune BALB/c) were incubated on monolayers of [C57BL/6 times BALB/cF1 (B6CF1) spleen cells on polylysine-coated polystyrene Petri plate, for 1/2 hr or for 1 hr at 37 degrees C followed by centrifugation of the monolayers for 5 min at 70 times G to 110 times G at 34 to 37 degrees C. Control monolayers were BALB/c spleen cells. As measured by the Simonsen spleen weight assay in neonatal mice, graft-vs-host (GVH) activity was partially depleted in cell populations nonadherent to B6CF1 monolayers. Residual GVH activity of these nonadherent cells was about half that of cells incubated on the control syngeneic monolayers (the mean of eight experiments was 49% +/- 11% S.D.). Two or three consecutive cycles of incubation and centrifugation did not significantly diminish the residual GVH activity, suggesting that spleen cells with GVH activity are heterogeneous with respect to binding to allogeneic target cells under the above conditions. Cell populations nonadherent to third-part [A times AL]F1 monolayers retained full activity, and cell populations partially depleted of GVH activity in B6CF1 neonates had full activity in third-party [BALB/c times AL]F1 neonates."}
{"id": "PMID:240887", "title": "Studies of surface immunoglobulins on human B lymphocytes. I. Dissociation of cell-bound immunoglobulins with acid pH or at 37 degrees C.", "content": "Lymphocyte preparations isolated from the human peripheral blood were exposed to different acid pH or incubated at 37 degrees C and the presence of immunoglobulin (Ig) on the cell surface was examined by immunofluorescence (IF) tests. Subsequently, such treated cells were incubated in the autologous serum or in the purified IgG, IgA or IgM proteins and their ability to bind each class of Ig was examined. The results showed that IgG molecules dissociated from large proportions of IgG-positive cells upon exposure to pH 4 at 1 degrees C for 1 min or upon incubation at 37 degrees C for 20 min. The cells from which IgG had been dissociated could again combine with IgG, whereupon the number of positive cells increased, being restored to the number of equivalent to or higher than those before acid or 37 degrees C treatment. These results indicated that the treatment could elute the cell-bound IgG present on the cell and that the receptor sites were not degraded by the treatment and could combine with IgG. These cell-bound IgG were observed not only on the monocytes, but also on the small lymphocytes. It was also found that certain proportions of mononuclear cells carried the cell-bound IgA that could be dissociated with acid pH or 37 degrees C. No cell-bound IgM was observed on any mononuclear cells. Microscopic observations before and after acid or 37 degrees C treatment revealed that the staining distribution of the cell-bound IgG and IgA on the cell was granular, appearing as a discontinuous fluorescence ring and forming multiple aggregates but no typical polar caps on warming. In contrast, IgG, IgA, and IgM stable to acid or 37 degrees C treatment were found on the lymphocytes but not on the monocytes, and their staining distribution was uniformaly diffuse, appearing as a continuous ring and forming a typical cap on warming. Exposure of the cells to pH 4 or 37 degrees C could also elute the cell-bound IgG passively adsorbed to the human lymphoid cells in a culture, but did not affect the intrinsic S.Ig on the lymphoid cells in a culture or on the lymphoma cells. These results indicate that the exposure of the cells to acid pH or to 37 degrees C may enable us to detect unfailingly S.Ig lymphocytes by removing the cell-bound IgG and IgA present on the monocytes and/or lymphocytes. Thus, an average value of approximately 10% was obtained for the S.Ig lymphocyte in the lymphocyte preparations from 11 healthy individuals. In addition, the results provided the evidence that, even in normal peripheral blood lymphocytes, there may be a population of B lymphocytes which lack the S.Ig but carry the cell-bound Ig.", "contents": "Studies of surface immunoglobulins on human B lymphocytes. I. Dissociation of cell-bound immunoglobulins with acid pH or at 37 degrees C. Lymphocyte preparations isolated from the human peripheral blood were exposed to different acid pH or incubated at 37 degrees C and the presence of immunoglobulin (Ig) on the cell surface was examined by immunofluorescence (IF) tests. Subsequently, such treated cells were incubated in the autologous serum or in the purified IgG, IgA or IgM proteins and their ability to bind each class of Ig was examined. The results showed that IgG molecules dissociated from large proportions of IgG-positive cells upon exposure to pH 4 at 1 degrees C for 1 min or upon incubation at 37 degrees C for 20 min. The cells from which IgG had been dissociated could again combine with IgG, whereupon the number of positive cells increased, being restored to the number of equivalent to or higher than those before acid or 37 degrees C treatment. These results indicated that the treatment could elute the cell-bound IgG present on the cell and that the receptor sites were not degraded by the treatment and could combine with IgG. These cell-bound IgG were observed not only on the monocytes, but also on the small lymphocytes. It was also found that certain proportions of mononuclear cells carried the cell-bound IgA that could be dissociated with acid pH or 37 degrees C. No cell-bound IgM was observed on any mononuclear cells. Microscopic observations before and after acid or 37 degrees C treatment revealed that the staining distribution of the cell-bound IgG and IgA on the cell was granular, appearing as a discontinuous fluorescence ring and forming multiple aggregates but no typical polar caps on warming. In contrast, IgG, IgA, and IgM stable to acid or 37 degrees C treatment were found on the lymphocytes but not on the monocytes, and their staining distribution was uniformaly diffuse, appearing as a continuous ring and forming a typical cap on warming. Exposure of the cells to pH 4 or 37 degrees C could also elute the cell-bound IgG passively adsorbed to the human lymphoid cells in a culture, but did not affect the intrinsic S.Ig on the lymphoid cells in a culture or on the lymphoma cells. These results indicate that the exposure of the cells to acid pH or to 37 degrees C may enable us to detect unfailingly S.Ig lymphocytes by removing the cell-bound IgG and IgA present on the monocytes and/or lymphocytes. Thus, an average value of approximately 10% was obtained for the S.Ig lymphocyte in the lymphocyte preparations from 11 healthy individuals. In addition, the results provided the evidence that, even in normal peripheral blood lymphocytes, there may be a population of B lymphocytes which lack the S.Ig but carry the cell-bound Ig."}
{"id": "PMID:240888", "title": "Secondary IgG responses to type III pneumococcal polysaccharide. I. Kinetics and antigen requirements.", "content": "Mice primed with a thymus- (T)3 dependent form of Type III pneumococcal polysaccharide (S3), i.e., S3 coupled to sheep or horse erythrocytes (S3-RBC), produce S3-specific IgG antibody after secondary challenge with either the T-dependent (S3-RBC) or T-independent (S3) form of the antigen. The potential to produce IgG antibody after challenge with S3-RBC appears earlier after priming than the potential to produce IgG after challenge with S3, suggesting that different \"memory\" cells may be involved in the two responses. The \"memory\" cells were shown to be S3-specific since S3 had to be present on the carrier in order for priming to occur and carrier specificity was not required for elicitation of the secondary response by S3-RBC.", "contents": "Secondary IgG responses to type III pneumococcal polysaccharide. I. Kinetics and antigen requirements. Mice primed with a thymus- (T)3 dependent form of Type III pneumococcal polysaccharide (S3), i.e., S3 coupled to sheep or horse erythrocytes (S3-RBC), produce S3-specific IgG antibody after secondary challenge with either the T-dependent (S3-RBC) or T-independent (S3) form of the antigen. The potential to produce IgG antibody after challenge with S3-RBC appears earlier after priming than the potential to produce IgG after challenge with S3, suggesting that different \"memory\" cells may be involved in the two responses. The \"memory\" cells were shown to be S3-specific since S3 had to be present on the carrier in order for priming to occur and carrier specificity was not required for elicitation of the secondary response by S3-RBC."}
{"id": "PMID:240889", "title": "7S class-restricted hapten-specific paralysis by injection of thymus-independent hapten-carrier conjugate.", "content": "The shift from IgM anti-hapten antibody production to IgG anti-hapten antibody production, subsequent to challenge with a T-dependent conjugate, is inhibited in mice by preimmunization with the T-independent DNP-LE conjugate. The results suggest that DNP on levan triggers off 19A T-independent anti-hapten precursors and paralyzes 7S T-dependent anti-hapten precursors.", "contents": "7S class-restricted hapten-specific paralysis by injection of thymus-independent hapten-carrier conjugate. The shift from IgM anti-hapten antibody production to IgG anti-hapten antibody production, subsequent to challenge with a T-dependent conjugate, is inhibited in mice by preimmunization with the T-independent DNP-LE conjugate. The results suggest that DNP on levan triggers off 19A T-independent anti-hapten precursors and paralyzes 7S T-dependent anti-hapten precursors."}
{"id": "PMID:240890", "title": "The elaboration of leukotactic mediators during the interaction between parental-type lymphocytes and F1 hybrid cells.", "content": "Mixed leukocyte cultures consisting of white blood cells from (Lewis times BN) F1 hybrids and Lewis parents produced monocyte chemotactic factor. Elaboration of this material preceded incorporation of 3H-thymidine. Local graft vs host (GVH) reactions were induced by subcapsular injection of parental thoracic duct cells into F1 hybrids. Homogenates from these kidneys, but not from kidneys injected with syngeneic thoracic duct cells, contained monocyte chemotactic factor. Little or no neutrophil chemotactic factor was present. Ultracentrifugal analysis of the monocyte chemotactic factor indicated a distribution similar to that found previously in culture fluids of lymphoid cells stimulated by soluble antigens. Differential counts of inflammatory cells extracted in suspension form from kidneys undergoing a GVH reaction indicated the majority of cells to be lymphocytic in type, but with a significant proportion of monocytes. Virtually no neutrophils were present. These findings indicate that a monocyte chemotactic factor is produced by cultures of parental leukocytes stimulated by semiallogeneic cells and that a similar factor appears in GVH reactions in the rat kidney. This chemotactic factor may be relevant to the character of the cellular exudates.", "contents": "The elaboration of leukotactic mediators during the interaction between parental-type lymphocytes and F1 hybrid cells. Mixed leukocyte cultures consisting of white blood cells from (Lewis times BN) F1 hybrids and Lewis parents produced monocyte chemotactic factor. Elaboration of this material preceded incorporation of 3H-thymidine. Local graft vs host (GVH) reactions were induced by subcapsular injection of parental thoracic duct cells into F1 hybrids. Homogenates from these kidneys, but not from kidneys injected with syngeneic thoracic duct cells, contained monocyte chemotactic factor. Little or no neutrophil chemotactic factor was present. Ultracentrifugal analysis of the monocyte chemotactic factor indicated a distribution similar to that found previously in culture fluids of lymphoid cells stimulated by soluble antigens. Differential counts of inflammatory cells extracted in suspension form from kidneys undergoing a GVH reaction indicated the majority of cells to be lymphocytic in type, but with a significant proportion of monocytes. Virtually no neutrophils were present. These findings indicate that a monocyte chemotactic factor is produced by cultures of parental leukocytes stimulated by semiallogeneic cells and that a similar factor appears in GVH reactions in the rat kidney. This chemotactic factor may be relevant to the character of the cellular exudates."}
{"id": "PMID:240891", "title": "Immunosuppression of normal lymphoid cells by serum from mice undergoing chronic graft-vs-host disease.", "content": "Spleen cells from F1 mice undergoing chronic graft-vs-host (GVH) reaction, induced by injection of parental cells, were shown to be immunosuppressed since their in vitro responses to the mitogens concanavalin A (Con A) and bacterial lipopolysaccharide (LPS) were substantially lower than control animals. Serum, from mice undergoing GVH, when cultured in vitro with normal spleen cells was immunosuppressive. The proliferation response to Con A and allogeneic cells of normal syngeneic, allogeneic, and parental spleen cells was 90% suppressed when serum from mice undergoing chronic GVH was added in comparison to the addition of serum from untreated F1 mice. Similarly, the in vitro antibody response to a T-dependent antigen was impaired; however, the antibody response to a T-independent antigen was not impaired. These results indicate that T cell functions are more sensitive than are B cell functions to immunosuppressive factors in the serum of mice undergoing GVH.", "contents": "Immunosuppression of normal lymphoid cells by serum from mice undergoing chronic graft-vs-host disease. Spleen cells from F1 mice undergoing chronic graft-vs-host (GVH) reaction, induced by injection of parental cells, were shown to be immunosuppressed since their in vitro responses to the mitogens concanavalin A (Con A) and bacterial lipopolysaccharide (LPS) were substantially lower than control animals. Serum, from mice undergoing GVH, when cultured in vitro with normal spleen cells was immunosuppressive. The proliferation response to Con A and allogeneic cells of normal syngeneic, allogeneic, and parental spleen cells was 90% suppressed when serum from mice undergoing chronic GVH was added in comparison to the addition of serum from untreated F1 mice. Similarly, the in vitro antibody response to a T-dependent antigen was impaired; however, the antibody response to a T-independent antigen was not impaired. These results indicate that T cell functions are more sensitive than are B cell functions to immunosuppressive factors in the serum of mice undergoing GVH."}
{"id": "PMID:240892", "title": "The interdomain disulfide bond of a homogeneous rabbit pneumococcal antibody light chain.", "content": "Rabbit light chain 3315, prepared from a homogeneous antipneumococcal antibody, was subjected to hydrolysis by pepsin without prior reduction and alkylation of the intrachain disulfide bonds. Gel filtration of the hydrolysate on Sephadex G-10, G-15, and G-25 and ion exchange chromatography on SP-Sephadex yielded several disulfide bridge peptides. These were fully reduced and alkulated and sequenced by Edman degradation. The peptides were located in the light chain sequence determined in independent studies from our laboratory. The half-cystine residues in this KB rabbit chain are located at positions 23, 80, 88, 134, 171, 194, and 214. The extra disulfide bridge extends between residues 80 and 171, thus joining the variable and constant domains. This is consistent with x-ray diffraction crystallographic studies showing that the corresponding residues in human light chains are separated by a distance compatible with disulfide bond formation.", "contents": "The interdomain disulfide bond of a homogeneous rabbit pneumococcal antibody light chain. Rabbit light chain 3315, prepared from a homogeneous antipneumococcal antibody, was subjected to hydrolysis by pepsin without prior reduction and alkylation of the intrachain disulfide bonds. Gel filtration of the hydrolysate on Sephadex G-10, G-15, and G-25 and ion exchange chromatography on SP-Sephadex yielded several disulfide bridge peptides. These were fully reduced and alkulated and sequenced by Edman degradation. The peptides were located in the light chain sequence determined in independent studies from our laboratory. The half-cystine residues in this KB rabbit chain are located at positions 23, 80, 88, 134, 171, 194, and 214. The extra disulfide bridge extends between residues 80 and 171, thus joining the variable and constant domains. This is consistent with x-ray diffraction crystallographic studies showing that the corresponding residues in human light chains are separated by a distance compatible with disulfide bond formation."}
{"id": "PMID:240893", "title": "Age-related changes in cell-mediated immunity in BALB/C mice.", "content": "The effect of increasing age on various tests of cell-mediated immunity was investigated in BALB/c mice both in vitro and in vivo with four different assay systems. The following results were obtained. 1) In contact sensitivity to DNFB, old mice (age 60 to 80 weeks) showed no differences in sensitization when compared to young adult mice (age 8 to 12 weeks). (In contrast, old NZB/W mice showed impaired contact sensitization when compared with young NZB/W MICE.)2) Unlike the reaction in contact sensitivity, cells from old BALB/c mice were defective in eliciting a graft-vs-host reaction. This was true also when a partially purified population of T cells was transferred. 3) In the mixed lymphocyte reaction, cells from old mice were as efficient or better than cells from young adult BALB/c mice in responding to or stimulating allogeneic cells. 4) Responses to PHA and Con A (Both T cell mitogens) were greatly reduced when old cells were cultured as compared with cells from young adult mice. Thus, we have found that within the same batch of mice, increasing age was associated with increased capabilities in some measures of cell-mediated immunologic function and decreased capabilities in other measures of the same.", "contents": "Age-related changes in cell-mediated immunity in BALB/C mice. The effect of increasing age on various tests of cell-mediated immunity was investigated in BALB/c mice both in vitro and in vivo with four different assay systems. The following results were obtained. 1) In contact sensitivity to DNFB, old mice (age 60 to 80 weeks) showed no differences in sensitization when compared to young adult mice (age 8 to 12 weeks). (In contrast, old NZB/W mice showed impaired contact sensitization when compared with young NZB/W MICE.)2) Unlike the reaction in contact sensitivity, cells from old BALB/c mice were defective in eliciting a graft-vs-host reaction. This was true also when a partially purified population of T cells was transferred. 3) In the mixed lymphocyte reaction, cells from old mice were as efficient or better than cells from young adult BALB/c mice in responding to or stimulating allogeneic cells. 4) Responses to PHA and Con A (Both T cell mitogens) were greatly reduced when old cells were cultured as compared with cells from young adult mice. Thus, we have found that within the same batch of mice, increasing age was associated with increased capabilities in some measures of cell-mediated immunologic function and decreased capabilities in other measures of the same."}
{"id": "PMID:240895", "title": "Correlation between mosquito repellent protection time and insensible water loss from the skin.", "content": "Insensible water loss and  mosquito repellent protection time have been found to be relatively characteristic of any given individual. In a population having a biologic distribution of repellent protection period against mosquitoes, an inverse linear correlation was observed between repellent duration and insensible water loss. Doubling of insensible water loss was associated with a 20% decrease in repellent duration. Repellent penetration or evaporation but not attractiveness to mosquitoes are explanations for the observed relationship.", "contents": "Correlation between mosquito repellent protection time and insensible water loss from the skin. Insensible water loss and  mosquito repellent protection time have been found to be relatively characteristic of any given individual. In a population having a biologic distribution of repellent protection period against mosquitoes, an inverse linear correlation was observed between repellent duration and insensible water loss. Doubling of insensible water loss was associated with a 20% decrease in repellent duration. Repellent penetration or evaporation but not attractiveness to mosquitoes are explanations for the observed relationship."}
{"id": "PMID:240898", "title": "Incubation studies on human red cells utilizing glucose or inosine under various conditions.", "content": "Human red cells were incubated at pH 8.2 and 30 mM phosphate concentration with glucose, glucose plus methylene blue, or inosine. In 16 normal subjects, the lactate production rate (LPR) from glucose alone was 92.2 +/- 7.5 mumoles per minute per liter red blood cell. With methylene blue added, the mean LPR was 118.5 +/- 7.4 per cent of control glucose values. With inosine as substrate the mean LPR was 68.5 +/- 6.0 per cent of that from glucose. Lactate/glucose ratios averaged 1.36, presumably because of accumulation of intermediates under conditions of high pH and Pi. Patients with various kinds of anemias had LPR's from glucose that were usually markedly higher than normal, but the LPR's from inosine were generally about 2/3 of those from glucose. The LPR's of the anemic patients correlated with their degree of reticulocytosis and several patients with pyruvate kinase (PK) deficiency showed normal LPR if the red cell population age was ignored, byt marked depression when compared to expected LPR for degree of reticulocytosis. The LPR from glucose of red cells of G6PD-deficient subjects was decreased (not increased) by methylene blue. Methylene blue, while stimulating the pentose phosphate pathway, also mediated some oxidation of NADH, thus complicating the stoichiometry of the overall system. In addition, the results suggested that the dye may have attacked -SH groups on some enzymes. In normal red cells, the lower LPR from inosine than from glucose was explained as due to consumption of ATP for hexose utilization (thus generating more ADP for the triose reactions). In confirmation, when red cells were incubated without substrate to deplete their ATP-, and enhance their ADP-, levels, the LPR from inosine exceeded that from glucose. Fluoride and iodoacetate affected LPR from glucose more than from inosine, suggesting the necessity of adequate ATP levels in hexose utilization. Overall glycolysis in the red cell is seen as the resultant of a network of metabolic reactions in which ADP and ATP levels are important control parameters.", "contents": "Incubation studies on human red cells utilizing glucose or inosine under various conditions. Human red cells were incubated at pH 8.2 and 30 mM phosphate concentration with glucose, glucose plus methylene blue, or inosine. In 16 normal subjects, the lactate production rate (LPR) from glucose alone was 92.2 +/- 7.5 mumoles per minute per liter red blood cell. With methylene blue added, the mean LPR was 118.5 +/- 7.4 per cent of control glucose values. With inosine as substrate the mean LPR was 68.5 +/- 6.0 per cent of that from glucose. Lactate/glucose ratios averaged 1.36, presumably because of accumulation of intermediates under conditions of high pH and Pi. Patients with various kinds of anemias had LPR's from glucose that were usually markedly higher than normal, but the LPR's from inosine were generally about 2/3 of those from glucose. The LPR's of the anemic patients correlated with their degree of reticulocytosis and several patients with pyruvate kinase (PK) deficiency showed normal LPR if the red cell population age was ignored, byt marked depression when compared to expected LPR for degree of reticulocytosis. The LPR from glucose of red cells of G6PD-deficient subjects was decreased (not increased) by methylene blue. Methylene blue, while stimulating the pentose phosphate pathway, also mediated some oxidation of NADH, thus complicating the stoichiometry of the overall system. In addition, the results suggested that the dye may have attacked -SH groups on some enzymes. In normal red cells, the lower LPR from inosine than from glucose was explained as due to consumption of ATP for hexose utilization (thus generating more ADP for the triose reactions). In confirmation, when red cells were incubated without substrate to deplete their ATP-, and enhance their ADP-, levels, the LPR from inosine exceeded that from glucose. Fluoride and iodoacetate affected LPR from glucose more than from inosine, suggesting the necessity of adequate ATP levels in hexose utilization. Overall glycolysis in the red cell is seen as the resultant of a network of metabolic reactions in which ADP and ATP levels are important control parameters."}
{"id": "PMID:240899", "title": "Synthesis of ethanolamine phosphoglycerides by human platelets.", "content": "Platelet homogenates contain an ethanolaminephosphotransferase (EC 2.7.8.1) that catalyzes the synthesis of ethanolamine phosphoglycerides from cytidine-5'-diphosphate ethanolamine and 1-radyl-2-acyl-sn-glycerols. The enzyme is particulate-bound and requires Mn2+ and bile salts for optimal activity. The apparent Km of the enzyme for cytidine-5'-diphosphate ethanolamine is 1.6 X 10(-5) M when the concentration of 1,2-diacyl-sn-glycerols is 8.8 X 10(-4) M. The pH optimum is 8.5 in Tris-HCl or glycine-NaOH buffer. The activity of the enzyme in platelets from normal subjects is 0.24-0.34 nmole/min/mg of protein.", "contents": "Synthesis of ethanolamine phosphoglycerides by human platelets. Platelet homogenates contain an ethanolaminephosphotransferase (EC 2.7.8.1) that catalyzes the synthesis of ethanolamine phosphoglycerides from cytidine-5'-diphosphate ethanolamine and 1-radyl-2-acyl-sn-glycerols. The enzyme is particulate-bound and requires Mn2+ and bile salts for optimal activity. The apparent Km of the enzyme for cytidine-5'-diphosphate ethanolamine is 1.6 X 10(-5) M when the concentration of 1,2-diacyl-sn-glycerols is 8.8 X 10(-4) M. The pH optimum is 8.5 in Tris-HCl or glycine-NaOH buffer. The activity of the enzyme in platelets from normal subjects is 0.24-0.34 nmole/min/mg of protein."}
{"id": "PMID:240900", "title": "Levels of luteinizing hormone, follicle-stimulating hormone, testosterone and dihydrotestosterone in the circulation of sexually maturing intact male rats and after orchidectomy and experimental bilateral cryptorchidism.", "content": "Plasma concentrations of LH, FSH, testosterone and dihydrotestosterone (DHT) have been measured in normal sexually maturing male rats from the age of 16-90 days. Between 16 and 25 days plasma testosterone levels were low, but rose suddenly on day 26. A similar increment occurred at the same time in plasma DHT levels, but this steroid reached its peak concentration later than testosterone. Plasma LH levels rose steadily from day 25 onwards, reaching their highest values on day 30. A marked increase in FSH levels was found on day 16, and a peak was reached on day 33 followed by a decline to a level characteristic of the adult. In addition, plasma levels of all these hormones were estimated in the male animals at various stages of development after orchidectomy and cryptorchidism. Four days after operation, the plasma levels of LH and FSH in the orchidectomized animals reached higher levels than those found in the intact animals, indicating the existence of a dynamic feedback relationship before puberty between gonadal steroids and pituitary gonadotrophic secretion. However, results from the experimental bilaterally cryptochid animals, suggested that the gonadal steriod-gonadotrophic feedback relationship could not be the only factor initiating puberty.", "contents": "Levels of luteinizing hormone, follicle-stimulating hormone, testosterone and dihydrotestosterone in the circulation of sexually maturing intact male rats and after orchidectomy and experimental bilateral cryptorchidism. Plasma concentrations of LH, FSH, testosterone and dihydrotestosterone (DHT) have been measured in normal sexually maturing male rats from the age of 16-90 days. Between 16 and 25 days plasma testosterone levels were low, but rose suddenly on day 26. A similar increment occurred at the same time in plasma DHT levels, but this steroid reached its peak concentration later than testosterone. Plasma LH levels rose steadily from day 25 onwards, reaching their highest values on day 30. A marked increase in FSH levels was found on day 16, and a peak was reached on day 33 followed by a decline to a level characteristic of the adult. In addition, plasma levels of all these hormones were estimated in the male animals at various stages of development after orchidectomy and cryptorchidism. Four days after operation, the plasma levels of LH and FSH in the orchidectomized animals reached higher levels than those found in the intact animals, indicating the existence of a dynamic feedback relationship before puberty between gonadal steroids and pituitary gonadotrophic secretion. However, results from the experimental bilaterally cryptochid animals, suggested that the gonadal steriod-gonadotrophic feedback relationship could not be the only factor initiating puberty."}
{"id": "PMID:240901", "title": "[Differentiation of haemopoietic tissues from embryos and adults injected into irradiated chickens (author's transl)].", "content": "Irradiated chicken are injected with haemopoietic tissues from adult or 11-day-old embryos. Development of stem cells gives rise to well-defined erythrocytic colonies on the surface of the tibial marrow. Erythropoietic production appears to be similar from adult marrow and embryonic blood stem cells; production from injected vitelline stem cells seems to be between 3 and 4 times higher than that of adult marrow stem cells. Results are discussed on the basis of two hypotheses: -existence of an extramedullary erythropoietic site in the host after vitelline cells grafting; -development of vitelline stem cells in the host marrow with kinetic patterns different from those of grafted adult marrow or embryonic blood stem cells. Anyway, the 11-day-old embryo appears to contain at least two types of blood stem cells with distinctive properties. Developmental origin, relationship and future of these different stem cells remain to be analysed.", "contents": "[Differentiation of haemopoietic tissues from embryos and adults injected into irradiated chickens (author's transl)]. Irradiated chicken are injected with haemopoietic tissues from adult or 11-day-old embryos. Development of stem cells gives rise to well-defined erythrocytic colonies on the surface of the tibial marrow. Erythropoietic production appears to be similar from adult marrow and embryonic blood stem cells; production from injected vitelline stem cells seems to be between 3 and 4 times higher than that of adult marrow stem cells. Results are discussed on the basis of two hypotheses: -existence of an extramedullary erythropoietic site in the host after vitelline cells grafting; -development of vitelline stem cells in the host marrow with kinetic patterns different from those of grafted adult marrow or embryonic blood stem cells. Anyway, the 11-day-old embryo appears to contain at least two types of blood stem cells with distinctive properties. Developmental origin, relationship and future of these different stem cells remain to be analysed."}
{"id": "PMID:240902", "title": "Positional information and pattern regulation in hydra: enzyme profiles.", "content": "Certain key enzymes of alternative pathways of glucose metabolism, of amino acid metabolism and of redox systems have been measured in hydra and this profile compared with mammalian differentiated tissues with a view to locating pathways of specific importance in hydra. There was a marked constant proportionality in the major part of the enzymes investigated, the profile suggested a metabolic pattern geared to utilization of amino acids as a carbon source for biosynthesis and energy production and to the production and conservation of pyruvate. The importance of conversion to ionized forms was noted. The most notable specific proportion changes were the exceptionally low lactate dehydrogenase, malic enzyme and the relatively high citrate synthase. The proximal-distal gradients in hydra were examined and these gradients suggested a switch to a more anaerobic type of metabolism and an elevation of the pentose phosphate pathway as the basal region was approached. Measurements of the formation of 14CO2 from specifically labelled glucose provided additional evidence for the functional activity and polarity of the pentose phosphate pathway in hydra. The effect of oligomycin, which can reverse polarity in hydra, had a significant effect on gradients of enzymes eliminating all except that observed for G6P dehydrogenase. The profile suggested a movement towards a more anaerobic type of metabolism, in keeping with the known biochemical action of this inhibitor. It is suggested that redox states and/or phosphorylation states may be featured in the positional information of cells in hydra.", "contents": "Positional information and pattern regulation in hydra: enzyme profiles. Certain key enzymes of alternative pathways of glucose metabolism, of amino acid metabolism and of redox systems have been measured in hydra and this profile compared with mammalian differentiated tissues with a view to locating pathways of specific importance in hydra. There was a marked constant proportionality in the major part of the enzymes investigated, the profile suggested a metabolic pattern geared to utilization of amino acids as a carbon source for biosynthesis and energy production and to the production and conservation of pyruvate. The importance of conversion to ionized forms was noted. The most notable specific proportion changes were the exceptionally low lactate dehydrogenase, malic enzyme and the relatively high citrate synthase. The proximal-distal gradients in hydra were examined and these gradients suggested a switch to a more anaerobic type of metabolism and an elevation of the pentose phosphate pathway as the basal region was approached. Measurements of the formation of 14CO2 from specifically labelled glucose provided additional evidence for the functional activity and polarity of the pentose phosphate pathway in hydra. The effect of oligomycin, which can reverse polarity in hydra, had a significant effect on gradients of enzymes eliminating all except that observed for G6P dehydrogenase. The profile suggested a movement towards a more anaerobic type of metabolism, in keeping with the known biochemical action of this inhibitor. It is suggested that redox states and/or phosphorylation states may be featured in the positional information of cells in hydra."}
{"id": "PMID:240903", "title": "Xenopus laevis cement gland as an experimental model for embryonic differentiation. I. In vitro stimulation of differentiation by ammonium chloride.", "content": "Ectoblastic cells explanted from the animal pole of young Xenopus laevis gastrulae have been cultured in vitro. When these cells were cultured for five days in standard salt solutions they formed atypical epidermis. When they were first submitted for 6 h to Holtfreter solution containing ammonium chloride and then transferred for five days in standard Barth's solution they underwent differentiation into typical cement gland tissue. The optimum concentration of ammonium chloride was 10 mM. Below and above this concentration the resulting cement glands had a smaller volume. The optimum duration for the initial stimulation with 10 mM ammonium chloride in Holtfreter solution was 6 h. Shorter stimulation times produced only small cement glands. Longer initial incubations in ammonium chloride resulted in progressive dissociation of the explants. To obtain the best differentiation into cement gland it appeared that the pH of the ammonium chloride solution should be between 7-5 and 7-7. When the stimulation is performed under these optimum conditions the cement gland measured after five days of culture accounts for 80-90 percent of the explanted tissue. This means that all or almost all of the competent superficial layer of the ectoblastic cells underwent differentiation into cement gland. No other differentiated tissue was observed in the explants. The cement gland is a very simple organ containing only one single cell type. The gland obtained under the described in vitro conditions is therefore proposed as an experimental model for biochemical studies on early embryonic differentiation.", "contents": "Xenopus laevis cement gland as an experimental model for embryonic differentiation. I. In vitro stimulation of differentiation by ammonium chloride. Ectoblastic cells explanted from the animal pole of young Xenopus laevis gastrulae have been cultured in vitro. When these cells were cultured for five days in standard salt solutions they formed atypical epidermis. When they were first submitted for 6 h to Holtfreter solution containing ammonium chloride and then transferred for five days in standard Barth's solution they underwent differentiation into typical cement gland tissue. The optimum concentration of ammonium chloride was 10 mM. Below and above this concentration the resulting cement glands had a smaller volume. The optimum duration for the initial stimulation with 10 mM ammonium chloride in Holtfreter solution was 6 h. Shorter stimulation times produced only small cement glands. Longer initial incubations in ammonium chloride resulted in progressive dissociation of the explants. To obtain the best differentiation into cement gland it appeared that the pH of the ammonium chloride solution should be between 7-5 and 7-7. When the stimulation is performed under these optimum conditions the cement gland measured after five days of culture accounts for 80-90 percent of the explanted tissue. This means that all or almost all of the competent superficial layer of the ectoblastic cells underwent differentiation into cement gland. No other differentiated tissue was observed in the explants. The cement gland is a very simple organ containing only one single cell type. The gland obtained under the described in vitro conditions is therefore proposed as an experimental model for biochemical studies on early embryonic differentiation."}
{"id": "PMID:240904", "title": "The function of hemocyanin in respiration of the blue crab Callinectes sapidus.", "content": "Blood PO2 in the blue crab Callinectes sapidus, a very active species of tropical origin, is lower at 22 degrees C than that of larger crabs in colder waters. These low oxygen levels permit its hemocyanin to be highly oxygenated at the gill, and to deliver almost half of its oxygen to the tissues in resting animals. Sustained muscular activity results in conspicuous decreases in blood PO2, pH and hemocyanin oxygenation. Although the venous reserve is fully utilized, hemocyanin oxygenation at the gill decreases so much that there is no change in its total quantitative function. The large Bohr shift becomes functional during activity, but its quantitative importance is not clear.", "contents": "The function of hemocyanin in respiration of the blue crab Callinectes sapidus. Blood PO2 in the blue crab Callinectes sapidus, a very active species of tropical origin, is lower at 22 degrees C than that of larger crabs in colder waters. These low oxygen levels permit its hemocyanin to be highly oxygenated at the gill, and to deliver almost half of its oxygen to the tissues in resting animals. Sustained muscular activity results in conspicuous decreases in blood PO2, pH and hemocyanin oxygenation. Although the venous reserve is fully utilized, hemocyanin oxygenation at the gill decreases so much that there is no change in its total quantitative function. The large Bohr shift becomes functional during activity, but its quantitative importance is not clear."}
{"id": "PMID:240905", "title": "The influence of environmental salinity on hemocyanin function in the blue crab, Callinectes sapidus.", "content": "The effects of inorganic ions and of the hydrogen ion on oxygen-binding properties of most respiratory pigments are opposite. The addition of salt to the medium increases oxygen affinities, and the addition of H+ decreases oxygen affinities of crustacean hemocyanins. These oxygenation properties, as observed in vitro, suggest that the oxygen-transport system must adapt to ionic changes in the blood. In fact, decreases in the salt concentration of the blood of estaurine blue crabs are accompanied by increases in pH, probably resulting from the input of ammonia produced in deamination of the intracellular pool of free amino acids as the cells conform to osmotic changes in body fluids. The result is a stability of hemocyanin function until the blood becomes very dilute. As the acclimation salinity is reduced from 35 to 15 o/ooo, the ionic effects on respiratory transport are balanced and there is no change in total oxygen uptake. At 5 o/ooo salinity, however, the higher blood pH is manifested in an elevation of the total oxygen concentration of prebranchial blood, probably because the Bohr shift is no longer opposed by a critical level of salt in the blood. Under these conditions the role of hemocyanin in aerobic respiration is reduced at high environmental oxygen levels, but it may be enhanced in hypoxic uaters.", "contents": "The influence of environmental salinity on hemocyanin function in the blue crab, Callinectes sapidus. The effects of inorganic ions and of the hydrogen ion on oxygen-binding properties of most respiratory pigments are opposite. The addition of salt to the medium increases oxygen affinities, and the addition of H+ decreases oxygen affinities of crustacean hemocyanins. These oxygenation properties, as observed in vitro, suggest that the oxygen-transport system must adapt to ionic changes in the blood. In fact, decreases in the salt concentration of the blood of estaurine blue crabs are accompanied by increases in pH, probably resulting from the input of ammonia produced in deamination of the intracellular pool of free amino acids as the cells conform to osmotic changes in body fluids. The result is a stability of hemocyanin function until the blood becomes very dilute. As the acclimation salinity is reduced from 35 to 15 o/ooo, the ionic effects on respiratory transport are balanced and there is no change in total oxygen uptake. At 5 o/ooo salinity, however, the higher blood pH is manifested in an elevation of the total oxygen concentration of prebranchial blood, probably because the Bohr shift is no longer opposed by a critical level of salt in the blood. Under these conditions the role of hemocyanin in aerobic respiration is reduced at high environmental oxygen levels, but it may be enhanced in hypoxic uaters."}
{"id": "PMID:240906", "title": "Voltage clamp analysis of two inward current mechanisms in the egg cell membrane of a starfish.", "content": "Ionic mechanisms of excitation were studied in the immature egg cell membrane of a starfish, Mediaster aequalis, by analyzing membrane currents during voltage clamp. The cell membrane shows two different inward current mechanisms. One is activated at a membrane potential of -55 approximately -50 mV and the other at -7 approximately -6 mV. They are referred to as channels I and II, respectively. A similar difference is also found in the membrane potential of half inactivation. Currents of the two channels can, therefore, be separated by selective inactivation. The currents of both channels depend on Ca++ (Sr++ or Ba++) but only the current of channel I depends on Na+. The time-course of current differs significantly between the two channels when compared at the same membrane potential. The relationship between the membrane current and the concentration of the permeant ions is also different between the two channels. The result suggests that channel II is a more saturable system. The sensitivity of the current to blocking cations such as Co++ or Mg++ is substantially greater in channel II than in channel I. Currents of both channels depend on the external pH with an apparent pK of 5.6. They are insensitive to 3 muM tetrodotoxin (TTX) but are eliminated totally by 7.3 mM procaine. The properties of channel II are similar to those of the Ca channel found in various adult tissues. The properties of channel I differ, however, from those of either the typical Ca or Na channels. Although the current of the channel depends on the external Na the amplitude of the Na current decreases not only with the Na concentration but also with the Ca concentration. No selectivity is found among Li+, Na+, Rb+, and Cs+. The experimental result suggests that Na+ does not carry current but modifies the current carried by Ca in channel I.", "contents": "Voltage clamp analysis of two inward current mechanisms in the egg cell membrane of a starfish. Ionic mechanisms of excitation were studied in the immature egg cell membrane of a starfish, Mediaster aequalis, by analyzing membrane currents during voltage clamp. The cell membrane shows two different inward current mechanisms. One is activated at a membrane potential of -55 approximately -50 mV and the other at -7 approximately -6 mV. They are referred to as channels I and II, respectively. A similar difference is also found in the membrane potential of half inactivation. Currents of the two channels can, therefore, be separated by selective inactivation. The currents of both channels depend on Ca++ (Sr++ or Ba++) but only the current of channel I depends on Na+. The time-course of current differs significantly between the two channels when compared at the same membrane potential. The relationship between the membrane current and the concentration of the permeant ions is also different between the two channels. The result suggests that channel II is a more saturable system. The sensitivity of the current to blocking cations such as Co++ or Mg++ is substantially greater in channel II than in channel I. Currents of both channels depend on the external pH with an apparent pK of 5.6. They are insensitive to 3 muM tetrodotoxin (TTX) but are eliminated totally by 7.3 mM procaine. The properties of channel II are similar to those of the Ca channel found in various adult tissues. The properties of channel I differ, however, from those of either the typical Ca or Na channels. Although the current of the channel depends on the external Na the amplitude of the Na current decreases not only with the Na concentration but also with the Ca concentration. No selectivity is found among Li+, Na+, Rb+, and Cs+. The experimental result suggests that Na+ does not carry current but modifies the current carried by Ca in channel I."}
{"id": "PMID:240907", "title": "Microspectrophotometry of rhodopsin and metarhodopsin in the moth Galleria.", "content": "Fresh, frozen sections of the photoreceptor layer of the compound eye of the moth Galleria have been examined by microspectrophotometry, using 4 times 8 mum measuring beams that sampled from approximately two to four rhabdoms. The principal visual pigment absorbs maximally at 510 nm (P510), and on irradiation is converted to a thermally stable, pH-insensitive metarhodopsin with lambda max at 484 nm (M484) and a 43% increase in molar extinction coefficient. Subsequently, short wavelength irradiation of the metarhodopsin photoregenerates some P510, but the absence of an isosbestic point the cycle of spectral changes is consistent with the presence of smaller amounts of violet-or ultraviolet-sensitive visual pigment(s) that also are converted to a blue-absorbing metarhodopsin. Difference spectra for both P510 and M484 were measured, using hydroxylamine. The 484-nm metarhodopsin is reversibly converted to a form with lambda max at 363 nm by high concentrations of glycerol. Dark regeneration of rhodopsin in vivo after several minutes exposure of thoroughly dark-adapted animals to full sunlight requires several days.", "contents": "Microspectrophotometry of rhodopsin and metarhodopsin in the moth Galleria. Fresh, frozen sections of the photoreceptor layer of the compound eye of the moth Galleria have been examined by microspectrophotometry, using 4 times 8 mum measuring beams that sampled from approximately two to four rhabdoms. The principal visual pigment absorbs maximally at 510 nm (P510), and on irradiation is converted to a thermally stable, pH-insensitive metarhodopsin with lambda max at 484 nm (M484) and a 43% increase in molar extinction coefficient. Subsequently, short wavelength irradiation of the metarhodopsin photoregenerates some P510, but the absence of an isosbestic point the cycle of spectral changes is consistent with the presence of smaller amounts of violet-or ultraviolet-sensitive visual pigment(s) that also are converted to a blue-absorbing metarhodopsin. Difference spectra for both P510 and M484 were measured, using hydroxylamine. The 484-nm metarhodopsin is reversibly converted to a form with lambda max at 363 nm by high concentrations of glycerol. Dark regeneration of rhodopsin in vivo after several minutes exposure of thoroughly dark-adapted animals to full sunlight requires several days."}
{"id": "PMID:240909", "title": "Synthesis of yeast wall glucan.", "content": "Saccharomyces cerevisiae was treated with a mixture of toluene and ethanol to make it permeable to small molecules. This treatment unmasked a glucan synthetase activity which was assayed with UDP-[U-14C]glucose. About 60% of the polymer formed was beta-(I leads to 3)glucan. No labelled lipids were detected. The 14C incorporated was recovered in a particulate membrane preparation isolated by differential centrifugation. When the particles themselves were assayed for glucosyl transfer activity none was found. The toluene-treated preparations also catalysed the transfer of mannosyl residues from GDP-mannose to polymeric materials by a process independent of glucosyl transfer.", "contents": "Synthesis of yeast wall glucan. Saccharomyces cerevisiae was treated with a mixture of toluene and ethanol to make it permeable to small molecules. This treatment unmasked a glucan synthetase activity which was assayed with UDP-[U-14C]glucose. About 60% of the polymer formed was beta-(I leads to 3)glucan. No labelled lipids were detected. The 14C incorporated was recovered in a particulate membrane preparation isolated by differential centrifugation. When the particles themselves were assayed for glucosyl transfer activity none was found. The toluene-treated preparations also catalysed the transfer of mannosyl residues from GDP-mannose to polymeric materials by a process independent of glucosyl transfer."}
{"id": "PMID:240912", "title": "The effects of drugs on psychiatric patients' performance on the Halstead-Reitan neuropsychological test battery.", "content": "The relationship between the type and amount of psychotropic drug ingestion was evaluated for 184 psychiatric patients using a complex battery of cognitive-sensory-motor tests (Halstead-Reitan). The total patients' group included 68 psychotic patients who were being treated with either phenothiazines or \"another drug,\" and 80 neurotically depressed patients who were taking either no drugs, phenothiazines, minor tranquilizers, tricyclic antidepressants, or sedatives. Little, if any, effect was noted in terms of psychological test performance when individual drug types were combined and considered in terms of dosage. However, upon a more specific analysis of the data, several suggestive trends occurred, demonstrating that individual drugs have variable effects and that some age groupings are more sensitive to drug effects than other groupings. As these trends were a result of a secondary analysis, further investigation was recommended in order to delineate the variables involved. For the present, this investigation has demonstrated the important influence of age and drug type variables upon patient neuropsychological test performance.", "contents": "The effects of drugs on psychiatric patients' performance on the Halstead-Reitan neuropsychological test battery. The relationship between the type and amount of psychotropic drug ingestion was evaluated for 184 psychiatric patients using a complex battery of cognitive-sensory-motor tests (Halstead-Reitan). The total patients' group included 68 psychotic patients who were being treated with either phenothiazines or \"another drug,\" and 80 neurotically depressed patients who were taking either no drugs, phenothiazines, minor tranquilizers, tricyclic antidepressants, or sedatives. Little, if any, effect was noted in terms of psychological test performance when individual drug types were combined and considered in terms of dosage. However, upon a more specific analysis of the data, several suggestive trends occurred, demonstrating that individual drugs have variable effects and that some age groupings are more sensitive to drug effects than other groupings. As these trends were a result of a secondary analysis, further investigation was recommended in order to delineate the variables involved. For the present, this investigation has demonstrated the important influence of age and drug type variables upon patient neuropsychological test performance."}
{"id": "PMID:240913", "title": "Lack of effect of increased pineal serotonin content on H3-tryptophan uptake.", "content": "Major increases in the serotonin concentrations of rat pineal organs were produced by administering Catron, a monoamine oxidase inhibitor, prior to autopsy, or by preincubating the glands with serotonin (3X10-4M). These increases had no effect on pineal uptake of H3-tryptophan, the amino acid precursor for serotonin. These observations provide further evidence that the control of serotonin synthesis involves an important \"open-loop\" component.", "contents": "Lack of effect of increased pineal serotonin content on H3-tryptophan uptake. Major increases in the serotonin concentrations of rat pineal organs were produced by administering Catron, a monoamine oxidase inhibitor, prior to autopsy, or by preincubating the glands with serotonin (3X10-4M). These increases had no effect on pineal uptake of H3-tryptophan, the amino acid precursor for serotonin. These observations provide further evidence that the control of serotonin synthesis involves an important \"open-loop\" component."}
{"id": "PMID:240914", "title": "Splenogonadal fusion-a rare congenital anomaly demonstrated by 99Tc-sulfur colloid imaging: case report.", "content": "A case report illustrating the value of spleen scanning in the diagnosis of a rare anomaly characterized by fusion of the spleen and left testis is described. This malformation results from faulty organogenesis during the fifth to the eighth week of fetal development. Only 65 cases have been reported in the world literature. In most instances, the anomaly is recognized as an incidental finding at autopsy or at surgical exploration of the abdomen. In 20% of cases the anomaly is associated with osseous malformations such as peromelia, ectromelia, micrognathia, and talipes.", "contents": "Splenogonadal fusion-a rare congenital anomaly demonstrated by 99Tc-sulfur colloid imaging: case report. A case report illustrating the value of spleen scanning in the diagnosis of a rare anomaly characterized by fusion of the spleen and left testis is described. This malformation results from faulty organogenesis during the fifth to the eighth week of fetal development. Only 65 cases have been reported in the world literature. In most instances, the anomaly is recognized as an incidental finding at autopsy or at surgical exploration of the abdomen. In 20% of cases the anomaly is associated with osseous malformations such as peromelia, ectromelia, micrognathia, and talipes."}
{"id": "PMID:240915", "title": "Technetium 99m-pyridoxylideneglutamate: a new hepatobiliary radiopharmaceutical. I. Experimental aspects.", "content": "The labeling of pyridoxal and the pyridoxylidene derivative of glutamic acid with 99mTc has been achieved by a simple autoclaving procedure. Technetium-99-m-pyridoxylideneglutamate (99mTc-PG) shows marked biliary excretion with accumulation of radioactivity in the gallbladder and intestines of experimental animals. This compound has been extensively investigated with a view to its application in the diagnosis of biliary disorders in man by scintigraphy. Both scintigraphic and quantitative distribution studies showed that 99mTc-PG passed rapidly through the mouse liver with progressive accumulation in the gallbladder, allowing visualization of this organ within 10 min of injection. In 30 min over 40% of the injected dose was excreted into the intestine with an equivalent amount appearing in the urine; however, renal activity remained low. Scintigraphic studies in dogs showed results similar to those obtained in mice. Studies of the toxicity in three animal species indicated a wide margin of safety for 99mTc-PG in the dose proposed for diagnostic purposes in humans.", "contents": "Technetium 99m-pyridoxylideneglutamate: a new hepatobiliary radiopharmaceutical. I. Experimental aspects. The labeling of pyridoxal and the pyridoxylidene derivative of glutamic acid with 99mTc has been achieved by a simple autoclaving procedure. Technetium-99-m-pyridoxylideneglutamate (99mTc-PG) shows marked biliary excretion with accumulation of radioactivity in the gallbladder and intestines of experimental animals. This compound has been extensively investigated with a view to its application in the diagnosis of biliary disorders in man by scintigraphy. Both scintigraphic and quantitative distribution studies showed that 99mTc-PG passed rapidly through the mouse liver with progressive accumulation in the gallbladder, allowing visualization of this organ within 10 min of injection. In 30 min over 40% of the injected dose was excreted into the intestine with an equivalent amount appearing in the urine; however, renal activity remained low. Scintigraphic studies in dogs showed results similar to those obtained in mice. Studies of the toxicity in three animal species indicated a wide margin of safety for 99mTc-PG in the dose proposed for diagnostic purposes in humans."}
{"id": "PMID:240916", "title": "Highly iodinated fibrinogen: a new thrombus-localizing agent.", "content": "We have examined radioiodinated fibrinogen prepared at high levels of iodination as an agent for improved in vivo thrombus detection. Fibrinogen containing 25, 50, and 100 atoms of iodine per molecule is prepared by an electrolytic procedure and is compared with conventional radiolabeled fibrinogen (less than 0.5 iodine atom per molecule) prepared by the iodine monochloride method. The level of iodination has little effect on the isotopic clottability of the product, but its degree of aggregation and its rate of blood clearance in experimental animals is strongly dependent on iodination level. Isotopic thrombus: blood ratios obtained in recently induced thrombi with the 25 atom per molecule preparation average about 50:1, twice as high as the ratios obtained with conventionally labeled fibrinogen.", "contents": "Highly iodinated fibrinogen: a new thrombus-localizing agent. We have examined radioiodinated fibrinogen prepared at high levels of iodination as an agent for improved in vivo thrombus detection. Fibrinogen containing 25, 50, and 100 atoms of iodine per molecule is prepared by an electrolytic procedure and is compared with conventional radiolabeled fibrinogen (less than 0.5 iodine atom per molecule) prepared by the iodine monochloride method. The level of iodination has little effect on the isotopic clottability of the product, but its degree of aggregation and its rate of blood clearance in experimental animals is strongly dependent on iodination level. Isotopic thrombus: blood ratios obtained in recently induced thrombi with the 25 atom per molecule preparation average about 50:1, twice as high as the ratios obtained with conventionally labeled fibrinogen."}
{"id": "PMID:240923", "title": "Prophylaxis against hypocalcemia in low-birth-weight infants requiring bicarbonate infusion.", "content": "Forty-eight low-birth-weight infants with varying degrees of respiratory distress were studied with respect to serum calcium concentration and urinary calcium excretion. Serum calcium decreased over the 24-hour study period in infants who did not receive calcium infusion. The decrease was greater in those receiving bicarbonate therapy for acidosis. Continuous calcium infusion at 1 mg/kg/hr sustained relatively normal serum calcium concentration, even in those infants who required bicarbonate. Since the changes in estimated extracellular calcium could not be accounted for by urinary excretion, a shift of calcium into bone was postulated.", "contents": "Prophylaxis against hypocalcemia in low-birth-weight infants requiring bicarbonate infusion. Forty-eight low-birth-weight infants with varying degrees of respiratory distress were studied with respect to serum calcium concentration and urinary calcium excretion. Serum calcium decreased over the 24-hour study period in infants who did not receive calcium infusion. The decrease was greater in those receiving bicarbonate therapy for acidosis. Continuous calcium infusion at 1 mg/kg/hr sustained relatively normal serum calcium concentration, even in those infants who required bicarbonate. Since the changes in estimated extracellular calcium could not be accounted for by urinary excretion, a shift of calcium into bone was postulated."}
{"id": "PMID:240926", "title": "The amplitude and the time course of the end-plate current at various pH levels in the frog sartorius muscle.", "content": "1. The amplitude and the time course of the end-plate current are dependent on the pH of the bathing solution. 2. When pH is changed from 5.4 to 9.4 the amplitude of the end-plate current is increased and its decay is speeded up. 3. The change in the amplitude seems to be a result of a variation of quantal content. 4. The change in the time course of the end-plate current is explained by assuming that the rate constants which determine the dissociation of the receptor-mediator complex are affected by a change in pH. 5. This speculation is supported by the finding that the effect of membrane potential on amplitude and time course of the end-plate current are dependent on pH of the bathing solution.", "contents": "The amplitude and the time course of the end-plate current at various pH levels in the frog sartorius muscle. 1. The amplitude and the time course of the end-plate current are dependent on the pH of the bathing solution. 2. When pH is changed from 5.4 to 9.4 the amplitude of the end-plate current is increased and its decay is speeded up. 3. The change in the amplitude seems to be a result of a variation of quantal content. 4. The change in the time course of the end-plate current is explained by assuming that the rate constants which determine the dissociation of the receptor-mediator complex are affected by a change in pH. 5. This speculation is supported by the finding that the effect of membrane potential on amplitude and time course of the end-plate current are dependent on pH of the bathing solution."}
{"id": "PMID:240927", "title": "The movement of potassium ions during electrical activity, and the kinetics of the recovery process, in the non-myelinated fibres of the garfish olfactory nerve.", "content": "1. An electrophysiological study was made with the sucrose gap of the compound action potential of the non-myelinated fibres of the garfish olfactory nerve at temperatures between 8 and 22 degrees C. The efflux of 42K with stimulation, and the post-tetanic hyperpolarization following a period of repetitive stimulation, were also studied. 2. At 22 degrees C the compound action potential (at zero conduction distance) reached its peak in about 5 msec and lasted about 12 msec; the conduction velocity was 19.4 cm/sec. The corresponding extrapolated values at 0 degrees C were: time to peak, 16 msec; duration, 37 msec; conduction velocity, 4.2 cm/sec. 3. The rate constant for resting potassium efflux (kr) was 0.0108 min-1 at 22 degrees C and 0.00489 min-1 at 0 degrees C. 4. The extra fractional loss of potassium with stimulation (ks) was 2.02 x 10(-4) impulse-1 at 22 degrees C and 4.41 x 10(-4) impulse-1 at 0 degrees C. 5. Raising the external potassium concentration, or addition of ouabain (1 mM), raised the resting rate of efflux of potassium. 6. The post-tetanic hyperpolarization, which reflects the electrogenic extrusion of sodium ions, indicated a rate constant for active sodium efflux at 22 degrees C of 0.47 min=1. 7. The rate constant was decreased by a 10 degrees C fall in temperature by a factor of 1.73. 8. Increasing the external potassium concentration increased the rate constant, apparently by potassium combining with some site with an equilibrium dissociation constant of 1.2 mMM. 9. The rate constant was decreased slightly in acidic solutions and increased slightly in alkaline solutions. 10. 14C-labelled ouabain was found to bind to the garfish olfactory nerve with an equilibrium dissociation constant of about 0.5 muM. The maximum saturable binding capacity, 22.3 p-mole/mg dry, suggests that there are about 350 sodium pumping sites per square micron membrane.", "contents": "The movement of potassium ions during electrical activity, and the kinetics of the recovery process, in the non-myelinated fibres of the garfish olfactory nerve. 1. An electrophysiological study was made with the sucrose gap of the compound action potential of the non-myelinated fibres of the garfish olfactory nerve at temperatures between 8 and 22 degrees C. The efflux of 42K with stimulation, and the post-tetanic hyperpolarization following a period of repetitive stimulation, were also studied. 2. At 22 degrees C the compound action potential (at zero conduction distance) reached its peak in about 5 msec and lasted about 12 msec; the conduction velocity was 19.4 cm/sec. The corresponding extrapolated values at 0 degrees C were: time to peak, 16 msec; duration, 37 msec; conduction velocity, 4.2 cm/sec. 3. The rate constant for resting potassium efflux (kr) was 0.0108 min-1 at 22 degrees C and 0.00489 min-1 at 0 degrees C. 4. The extra fractional loss of potassium with stimulation (ks) was 2.02 x 10(-4) impulse-1 at 22 degrees C and 4.41 x 10(-4) impulse-1 at 0 degrees C. 5. Raising the external potassium concentration, or addition of ouabain (1 mM), raised the resting rate of efflux of potassium. 6. The post-tetanic hyperpolarization, which reflects the electrogenic extrusion of sodium ions, indicated a rate constant for active sodium efflux at 22 degrees C of 0.47 min=1. 7. The rate constant was decreased by a 10 degrees C fall in temperature by a factor of 1.73. 8. Increasing the external potassium concentration increased the rate constant, apparently by potassium combining with some site with an equilibrium dissociation constant of 1.2 mMM. 9. The rate constant was decreased slightly in acidic solutions and increased slightly in alkaline solutions. 10. 14C-labelled ouabain was found to bind to the garfish olfactory nerve with an equilibrium dissociation constant of about 0.5 muM. The maximum saturable binding capacity, 22.3 p-mole/mg dry, suggests that there are about 350 sodium pumping sites per square micron membrane."}
{"id": "PMID:240928", "title": "Binomial analysis of quantal transmitter release at glycerol treated frog neuromuscular junctions.", "content": "1. Transmitter release was analysed at frog neuromuscular junctions pre-treated with 400 mM glycerol Ringer. In the absence of added drugs, end-plate potentials (e.p.p.s) and miniature e.p.p.s (m.e.p.p.s) could be recorded at selected junctions. 2. E.p.p.s were unusually large and calculations of quantal content indicated a high level of release. Also recorded were anomalous action potentials resembling e.p.p.s but these could be distinguished using a summation test. 3. Plots of coefficient of variation of e.p.p.s (0-5 Hz stimulation) versus direct quantal content (M1) showed a marked deviation from Poisson expectations with high M1. Analysis of these results with amplitude-frequency histograms showed a progressively better fit to binomial predictions with increasing M1. 4. The use of binomial statistics allowed direct calculations of the mean probability of release (p) and the readily available store (n). Increasing Ca/Mg caused increases in both n and p. 5. Plots of M1 vs. Ca/Mg showed a power relationship of 3.58. Maximum m.e.p.p. amplitude occurred at control Ca/Mg. Both results were consistent with studies in muscles not treated with glycerol and indicated that glycerol treatment caused no major alterations pre- or post-junctionally. 6. Estimates of quantum size using Poisson assumptions showed an over-all increase when stimulus frequency was raised, indicating a shift from binomial to a Poisson distribution. 7. The combined findings demonstrate that the glycerol treated preparation can be used to examine the release process during high output. Such release conforms to binomial statistics and allows direct determinations of the parameters n and p.", "contents": "Binomial analysis of quantal transmitter release at glycerol treated frog neuromuscular junctions. 1. Transmitter release was analysed at frog neuromuscular junctions pre-treated with 400 mM glycerol Ringer. In the absence of added drugs, end-plate potentials (e.p.p.s) and miniature e.p.p.s (m.e.p.p.s) could be recorded at selected junctions. 2. E.p.p.s were unusually large and calculations of quantal content indicated a high level of release. Also recorded were anomalous action potentials resembling e.p.p.s but these could be distinguished using a summation test. 3. Plots of coefficient of variation of e.p.p.s (0-5 Hz stimulation) versus direct quantal content (M1) showed a marked deviation from Poisson expectations with high M1. Analysis of these results with amplitude-frequency histograms showed a progressively better fit to binomial predictions with increasing M1. 4. The use of binomial statistics allowed direct calculations of the mean probability of release (p) and the readily available store (n). Increasing Ca/Mg caused increases in both n and p. 5. Plots of M1 vs. Ca/Mg showed a power relationship of 3.58. Maximum m.e.p.p. amplitude occurred at control Ca/Mg. Both results were consistent with studies in muscles not treated with glycerol and indicated that glycerol treatment caused no major alterations pre- or post-junctionally. 6. Estimates of quantum size using Poisson assumptions showed an over-all increase when stimulus frequency was raised, indicating a shift from binomial to a Poisson distribution. 7. The combined findings demonstrate that the glycerol treated preparation can be used to examine the release process during high output. Such release conforms to binomial statistics and allows direct determinations of the parameters n and p."}
{"id": "PMID:240929", "title": "Chloride transport in human red cells.", "content": "1. The chloride equilibrium flux (chloride self-exchange) was determined by measuring the rate of 36Cl efflux from radioactively labelled human red cells. The cellular chloride concentration was varied between 5 and 700 mM by the nystatin technique (Cass & Dalmark, 1973). The chloride transport capacity was not affected by the nystatin technique. 2. The chloride equilibrium flux showed saturation kinetics in the pH range between 6-2 and 9-2 (0 degrees C). The chloride transport decreased at chloride concentrations higher than those which  gave the maximum transport. 3. The apparent half-saturation constant, (K1/2), depended on the pH and whether the chloride transport was perceived as a function of the chloride concentration in the medium or in the cell water. The (K1/2)m increased and the (K1/2)c decreased with increasing pH. The dependence of the chloride transport on the chloride concentration was described by Michaelis-Menten kinetics at pH 7-2, but at values of pH outside pH 7-8 S-shaped or steeper graphs were observed. 4. The chloride equilibrium flux varied with the pH at constant chloride concentration in the medium (pH 5-7-9-5). The transport had a bell-shaped pH dependence at chloride concentrations below 200 mM. At chloride concentrations between 300 and 600 mM the chloride transport increased with increasing pH to reach a plateau around pH 8. The position of the acidic branches of the pH graphs was independent of the chloride concentration (25-600 mM), but the position of the alkaline branches moved towards higher values of pH with increasing chloride concentration (5-150 mM). Thus, the position of the pH optimum increased with increasing chloride concentration. The chloride transport at low pH values was a function of the inverse second power of the hydrogen ion concentration. The pK of the groups which caused the inhibition was approximately 6 and independent of the temperature (0-18 degrees C). 5. The chloride equilibrium flux as a function of chloride concentration, pH, and temperature could be described by a transport model with a mobile, positively charged, chloride binding carrier with a single chloride dissociation constant of 33 mM, a transport capacity of 900 m-mole/3 x 10(13) cells.min (pH 7-2, 0 degrees C), and an Arrhenius activation energy of 30 kcal/mole. The pH dependence of the transport of inorganic monovalent and divalent anions is discussed in relation to the suggested model.", "contents": "Chloride transport in human red cells. 1. The chloride equilibrium flux (chloride self-exchange) was determined by measuring the rate of 36Cl efflux from radioactively labelled human red cells. The cellular chloride concentration was varied between 5 and 700 mM by the nystatin technique (Cass & Dalmark, 1973). The chloride transport capacity was not affected by the nystatin technique. 2. The chloride equilibrium flux showed saturation kinetics in the pH range between 6-2 and 9-2 (0 degrees C). The chloride transport decreased at chloride concentrations higher than those which  gave the maximum transport. 3. The apparent half-saturation constant, (K1/2), depended on the pH and whether the chloride transport was perceived as a function of the chloride concentration in the medium or in the cell water. The (K1/2)m increased and the (K1/2)c decreased with increasing pH. The dependence of the chloride transport on the chloride concentration was described by Michaelis-Menten kinetics at pH 7-2, but at values of pH outside pH 7-8 S-shaped or steeper graphs were observed. 4. The chloride equilibrium flux varied with the pH at constant chloride concentration in the medium (pH 5-7-9-5). The transport had a bell-shaped pH dependence at chloride concentrations below 200 mM. At chloride concentrations between 300 and 600 mM the chloride transport increased with increasing pH to reach a plateau around pH 8. The position of the acidic branches of the pH graphs was independent of the chloride concentration (25-600 mM), but the position of the alkaline branches moved towards higher values of pH with increasing chloride concentration (5-150 mM). Thus, the position of the pH optimum increased with increasing chloride concentration. The chloride transport at low pH values was a function of the inverse second power of the hydrogen ion concentration. The pK of the groups which caused the inhibition was approximately 6 and independent of the temperature (0-18 degrees C). 5. The chloride equilibrium flux as a function of chloride concentration, pH, and temperature could be described by a transport model with a mobile, positively charged, chloride binding carrier with a single chloride dissociation constant of 33 mM, a transport capacity of 900 m-mole/3 x 10(13) cells.min (pH 7-2, 0 degrees C), and an Arrhenius activation energy of 30 kcal/mole. The pH dependence of the transport of inorganic monovalent and divalent anions is discussed in relation to the suggested model."}
{"id": "PMID:240930", "title": "Chloride and water distribution in human red cells.", "content": "1. The influence of the pH and the temperature on the cellular chloride and water content was investigated in human red cells, the cellular KC1 concentrations of which varied between 10 and 600 mM. The compositions of the media (10-600 mM-KC1, 1 mM-NaC1, 27 mM sucrose) at each single KC1 concentration were constant at the different values of the pH and the temperature. 2. The variation of the cellular KC1 concentration was obtained by washing the cells with KC1 salt solutions containing nystatin...", "contents": "Chloride and water distribution in human red cells. 1. The influence of the pH and the temperature on the cellular chloride and water content was investigated in human red cells, the cellular KC1 concentrations of which varied between 10 and 600 mM. The compositions of the media (10-600 mM-KC1, 1 mM-NaC1, 27 mM sucrose) at each single KC1 concentration were constant at the different values of the pH and the temperature. 2. The variation of the cellular KC1 concentration was obtained by washing the cells with KC1 salt solutions containing nystatin..."}
{"id": "PMID:240931", "title": "Uptake of 5-methyltetrahydrofolic acid by the rat jejunum.", "content": "1. Everted sacs of rat jejunum were used to study the transport of 5-methyltetrahydrofolic acid at various concentrations and at different pHs. 2. The transport of 5-methyltetrahydrofolic acid appeared to be linear with increasing incubation time at a 5-methyltetrahydrofolic acid concentration of 10(-5) M in the incubating medium. Tissue uptake was much higher than serosal uptake. 3. At 'zero' concentration gradient of 5-methyltetrahydrofolic acid, the transport from mucosal to serosal sides was negligible but tissue uptake was appreciable. 4. Reducing the incubation temperature from 37 to 27 degrees C gave a Q10 value of 1-8. 5. The characteristics of 5-methyltetrahydrofolic acid uptake suggested a non-saturable transport mechanism. 6. Studies were also carried out with isolated mucosal epithelial cells at different incubation times and at different pH values. 7. The over-all results suggest that 5-methyltetrahydrofolic acid transport is most likely a passive diffusion of its zwitterion and also a solvent drag with water flow. 8. The 5-methyltetrahydrofolic acid may be converted to its zwitterion in an acid microclimate at the surface of the intestinal absorbing cell.", "contents": "Uptake of 5-methyltetrahydrofolic acid by the rat jejunum. 1. Everted sacs of rat jejunum were used to study the transport of 5-methyltetrahydrofolic acid at various concentrations and at different pHs. 2. The transport of 5-methyltetrahydrofolic acid appeared to be linear with increasing incubation time at a 5-methyltetrahydrofolic acid concentration of 10(-5) M in the incubating medium. Tissue uptake was much higher than serosal uptake. 3. At 'zero' concentration gradient of 5-methyltetrahydrofolic acid, the transport from mucosal to serosal sides was negligible but tissue uptake was appreciable. 4. Reducing the incubation temperature from 37 to 27 degrees C gave a Q10 value of 1-8. 5. The characteristics of 5-methyltetrahydrofolic acid uptake suggested a non-saturable transport mechanism. 6. Studies were also carried out with isolated mucosal epithelial cells at different incubation times and at different pH values. 7. The over-all results suggest that 5-methyltetrahydrofolic acid transport is most likely a passive diffusion of its zwitterion and also a solvent drag with water flow. 8. The 5-methyltetrahydrofolic acid may be converted to its zwitterion in an acid microclimate at the surface of the intestinal absorbing cell."}
{"id": "PMID:240932", "title": "Tonic release of transmitter at the neuromuscular junction of the crab.", "content": "1. Synaptic transmission was studied at the neuromuscular junction of the crab Ocypoda cursor, using conventional electrophysiological technique. 2. It was found that fibres of the extensor muscle and those composing the internal layer of the closer muscle have only post-synaptic inhibition (S fibres) while the fibres at the external layer of the closer muscle have in addition presynaptic inhibition (R fibres). 3. In S fibres, addition of GABA reduces input membrane resistance (Rm) and e.p.s.p. amplitude approximately to the same degree. The effect shows desensitization. In R type fibres, GABA reduces the e.p.s.p. much more than expected from changes in Rm. The post-synaptic effect of GABA on Rm shows desensitization, while the presynaptic effect does not show desensitization. 4. In about 50 percent of the cases, after desensitization occurred, Rm increased by about 10-30 percent above the control. Similar increase in Rm occurred after application of picrotoxin. These results suggest that initially the membrane resistance was lower due to tonic release of inhibitory transmitter. 5. The Q10 of Rm was found to vary between 2 and 3. In Ca2+ free media, Cl- free media, or in picrotoxin the Q10 is about 1-3. 6. In R fibres, addition of picrotoxin increased the amplitude of the e.p.s.p. by 30-60 percent above the expected increase due to changes in Rm. 7. In S fibres the mean slope of log e.p.s.p. vs. log [Ca2+] was found to be 1-63, while in R fibres the slope was 0-93. These results suggest the presence of tonic release of the inhibitory transmitter which acts both post-synaptically and presynaptically.", "contents": "Tonic release of transmitter at the neuromuscular junction of the crab. 1. Synaptic transmission was studied at the neuromuscular junction of the crab Ocypoda cursor, using conventional electrophysiological technique. 2. It was found that fibres of the extensor muscle and those composing the internal layer of the closer muscle have only post-synaptic inhibition (S fibres) while the fibres at the external layer of the closer muscle have in addition presynaptic inhibition (R fibres). 3. In S fibres, addition of GABA reduces input membrane resistance (Rm) and e.p.s.p. amplitude approximately to the same degree. The effect shows desensitization. In R type fibres, GABA reduces the e.p.s.p. much more than expected from changes in Rm. The post-synaptic effect of GABA on Rm shows desensitization, while the presynaptic effect does not show desensitization. 4. In about 50 percent of the cases, after desensitization occurred, Rm increased by about 10-30 percent above the control. Similar increase in Rm occurred after application of picrotoxin. These results suggest that initially the membrane resistance was lower due to tonic release of inhibitory transmitter. 5. The Q10 of Rm was found to vary between 2 and 3. In Ca2+ free media, Cl- free media, or in picrotoxin the Q10 is about 1-3. 6. In R fibres, addition of picrotoxin increased the amplitude of the e.p.s.p. by 30-60 percent above the expected increase due to changes in Rm. 7. In S fibres the mean slope of log e.p.s.p. vs. log [Ca2+] was found to be 1-63, while in R fibres the slope was 0-93. These results suggest the presence of tonic release of the inhibitory transmitter which acts both post-synaptically and presynaptically."}
{"id": "PMID:240933", "title": "Adrenergic influences on the electrical potential across the colonic mucosa of the rabbit.", "content": "1. An investigation was undertaken of the role of adrenergic influences on the transient change in colonic potential difference (p.d.) induced by handling in the rabbit. 2. P.d. was increased from 9-5 +/- 0-5 to 27-05 +/- 1-94 mV during a 2 hr period of handling and wrapping. Atropine and alpha-adrenergic block during this 2 hr period did not alter the magnitude of the response and the response in adrenalectomized animals was not significantly different from that of normal animals. 3. 'Total' adrenergic block and selective beta-adrenergic block abolished the change in p.d. with handling and infusion of an alpha-receptor agonist during the 2 hr period significantly reduced the response. 4. The changes in colonic p.d. with handling were greatly increased by the infusion of a beta-receptor agonist during the 2 hr test period. 5. The results indicate that the change in colonic p.d. with handling is a direct effect of the autonomic nervous system mediated via beta-receptors and that the changes were not related to the effects of circulating catecholamines or to changes in aldosterone production.", "contents": "Adrenergic influences on the electrical potential across the colonic mucosa of the rabbit. 1. An investigation was undertaken of the role of adrenergic influences on the transient change in colonic potential difference (p.d.) induced by handling in the rabbit. 2. P.d. was increased from 9-5 +/- 0-5 to 27-05 +/- 1-94 mV during a 2 hr period of handling and wrapping. Atropine and alpha-adrenergic block during this 2 hr period did not alter the magnitude of the response and the response in adrenalectomized animals was not significantly different from that of normal animals. 3. 'Total' adrenergic block and selective beta-adrenergic block abolished the change in p.d. with handling and infusion of an alpha-receptor agonist during the 2 hr period significantly reduced the response. 4. The changes in colonic p.d. with handling were greatly increased by the infusion of a beta-receptor agonist during the 2 hr test period. 5. The results indicate that the change in colonic p.d. with handling is a direct effect of the autonomic nervous system mediated via beta-receptors and that the changes were not related to the effects of circulating catecholamines or to changes in aldosterone production."}
{"id": "PMID:240934", "title": "The relative importance of central nervous catecholaminergic and cholinergic mechanisms in drinking in response to antiotensin and other thirst stimuli.", "content": "1. Intracranial or subcutaneous doses of atropine or atropine methyl nitrate that were fully effective at preventing drinking in response to intracranial carbachol did not block angiotensin-induced drinking. 2. The nicotinic antagonist dihydro-beta-erythroidine given intracranially affected neither angiotensin- nor carbachol-induced drinking. 3. The dopaminergic antagonists haloperidol and spiroperidol injected intracranially blocked angiotensin-induced drinking but did not affect carbachol-induced drinking. 4. Angiotensin- and carbachol-induced drinking were unaffected by alpha- or beta-adrenergic antagonists except at toxic doses. 5. Destruction of catecholaminergic neurones with 6-hydroxydopamine markedly reduced angiotensin-induced drinking, but had relatively little effect on carbachol-induced drinking. 6. Intracranial haloperidol reduced the amount of water drunk in response to overnight deprivation of water, but did not affect feeding in response to overnight starvation or to intracranial noradrenaline. 7. Drinking following overnight water deprivation was unaffected by intracranial alpha- or beta-adrenergic antagonists. 8. Preventing dopaminergic transmission with intracranial haloperidol decreased the water to food ratio of the rat's intake after overnight starvation, whereas increasing the dopamine levels with the combination of FLA-63 and L-DOPA increased the ratio. 9. Intraventricular dopamine in large amounts caused the water-replete rat to drink. 10. It is concluded that among the many functions of dopaminergic systems in the brain is a role in the control of water intake, and that these systems participate in an important way in drinking in response to angiotensin.", "contents": "The relative importance of central nervous catecholaminergic and cholinergic mechanisms in drinking in response to antiotensin and other thirst stimuli. 1. Intracranial or subcutaneous doses of atropine or atropine methyl nitrate that were fully effective at preventing drinking in response to intracranial carbachol did not block angiotensin-induced drinking. 2. The nicotinic antagonist dihydro-beta-erythroidine given intracranially affected neither angiotensin- nor carbachol-induced drinking. 3. The dopaminergic antagonists haloperidol and spiroperidol injected intracranially blocked angiotensin-induced drinking but did not affect carbachol-induced drinking. 4. Angiotensin- and carbachol-induced drinking were unaffected by alpha- or beta-adrenergic antagonists except at toxic doses. 5. Destruction of catecholaminergic neurones with 6-hydroxydopamine markedly reduced angiotensin-induced drinking, but had relatively little effect on carbachol-induced drinking. 6. Intracranial haloperidol reduced the amount of water drunk in response to overnight deprivation of water, but did not affect feeding in response to overnight starvation or to intracranial noradrenaline. 7. Drinking following overnight water deprivation was unaffected by intracranial alpha- or beta-adrenergic antagonists. 8. Preventing dopaminergic transmission with intracranial haloperidol decreased the water to food ratio of the rat's intake after overnight starvation, whereas increasing the dopamine levels with the combination of FLA-63 and L-DOPA increased the ratio. 9. Intraventricular dopamine in large amounts caused the water-replete rat to drink. 10. It is concluded that among the many functions of dopaminergic systems in the brain is a role in the control of water intake, and that these systems participate in an important way in drinking in response to angiotensin."}
{"id": "PMID:240935", "title": "Ionic dependence of luteinizing-hormone-induced steroidogenesis in the rabbit ovary.", "content": "1. Investigations were made into the influence of the ionic environment on the steroidogenic response of the rabbit ovary to luteinizing hormone (LH). 2. Removal of Ca2+ from the medium was without effect on the response to LH. A similar result was obtained in Ca2+-free medium containing EGTA. 3. A tenfold increase in [Ca2+]o to 25.6 mM, or the addition of La3+ or Eu3+ (0.25 mM) to medium containing the normal concentration of Ca2+, caused a marked inhibition of the response to LH. 4. Removal of Na+ from the medium, and replacement by choline, had no effect on the response to LH. Replacement of Na+ by Li+ inhibited the response to the hormone strongly, but the addition of 4 mM-Li+ to normal medium was without effect. 5. Removal of K+ from the medium inhibited LH-induced steroidogenesis, whereas a twentyfold increase in [K+]o to 100 mM had no effect. The response to LH was also unaffected by the absence of Cl-. 6. Ouabain (10(-4) M) inhbited the response to LH, but nupercaine (10(-4) M) was without effect. 7. The inhibitory effect of ouabain was reversed by the addition of 2 mM-NADP+ to the medium. In contrast, the inhibitory effect of Eu3+ persisted in the NADP+-rich medium. 8. It is suggested that the intracellular ratio of Na+ or Li+) to K+ is important for the expression of the steroidogenic response of the ovary to LH. Altered concentrations of these ions might affect the formation or availability of NADP+. The inhibitory effects of high [Ca2+]o and lanthanide ions, however, are probably due to inhibition of hormone-stimulated adenyl cyclase.", "contents": "Ionic dependence of luteinizing-hormone-induced steroidogenesis in the rabbit ovary. 1. Investigations were made into the influence of the ionic environment on the steroidogenic response of the rabbit ovary to luteinizing hormone (LH). 2. Removal of Ca2+ from the medium was without effect on the response to LH. A similar result was obtained in Ca2+-free medium containing EGTA. 3. A tenfold increase in [Ca2+]o to 25.6 mM, or the addition of La3+ or Eu3+ (0.25 mM) to medium containing the normal concentration of Ca2+, caused a marked inhibition of the response to LH. 4. Removal of Na+ from the medium, and replacement by choline, had no effect on the response to LH. Replacement of Na+ by Li+ inhibited the response to the hormone strongly, but the addition of 4 mM-Li+ to normal medium was without effect. 5. Removal of K+ from the medium inhibited LH-induced steroidogenesis, whereas a twentyfold increase in [K+]o to 100 mM had no effect. The response to LH was also unaffected by the absence of Cl-. 6. Ouabain (10(-4) M) inhbited the response to LH, but nupercaine (10(-4) M) was without effect. 7. The inhibitory effect of ouabain was reversed by the addition of 2 mM-NADP+ to the medium. In contrast, the inhibitory effect of Eu3+ persisted in the NADP+-rich medium. 8. It is suggested that the intracellular ratio of Na+ or Li+) to K+ is important for the expression of the steroidogenic response of the ovary to LH. Altered concentrations of these ions might affect the formation or availability of NADP+. The inhibitory effects of high [Ca2+]o and lanthanide ions, however, are probably due to inhibition of hormone-stimulated adenyl cyclase."}
{"id": "PMID:240936", "title": "The team; new roles for nurses in general practice--a lesson from America.", "content": "IN NORTH AMERICA ATTEMPTS HAVE BEEN MADE TO COUNTERACT THE SHORTAGE OF DOCTORS BY TRAINING ANCILLARIES: the physician's assistant (P.A.) and the family nurse practitioner (FNP). Though physician assistants may give rise to interpersonal difficulties within practices the concept of the family nurse practitioner has much application in Britain. The possibility of employing family nurse practitioners in British general practice is discussed particularly with regard to the help they might give in diagnosis, in psycho-social counselling and follow-up.", "contents": "The team; new roles for nurses in general practice--a lesson from America. IN NORTH AMERICA ATTEMPTS HAVE BEEN MADE TO COUNTERACT THE SHORTAGE OF DOCTORS BY TRAINING ANCILLARIES: the physician's assistant (P.A.) and the family nurse practitioner (FNP). Though physician assistants may give rise to interpersonal difficulties within practices the concept of the family nurse practitioner has much application in Britain. The possibility of employing family nurse practitioners in British general practice is discussed particularly with regard to the help they might give in diagnosis, in psycho-social counselling and follow-up."}
{"id": "PMID:240938", "title": "Alkylating analogs of bradykinin.", "content": "Three analogs of bradykinin have been synthesized which bear a bromoacetyl function on the alpha-amino group or on an anilinic amino group at position 5 or 8. It was hoped that one or more of these analogs might act as an irreversible bradykinin antagonist or as a long-acting converting enzyme inhibitor. Although none of the analogs exhibited the desired pharmacological properties, the methods described for the synthesis and characterization of peptides bearing anilinic bromoacetyl groups are of potential utility in the development of antagonists of other tyrosine--or phenylalanine--containing peptides.", "contents": "Alkylating analogs of bradykinin. Three analogs of bradykinin have been synthesized which bear a bromoacetyl function on the alpha-amino group or on an anilinic amino group at position 5 or 8. It was hoped that one or more of these analogs might act as an irreversible bradykinin antagonist or as a long-acting converting enzyme inhibitor. Although none of the analogs exhibited the desired pharmacological properties, the methods described for the synthesis and characterization of peptides bearing anilinic bromoacetyl groups are of potential utility in the development of antagonists of other tyrosine--or phenylalanine--containing peptides."}
{"id": "PMID:240939", "title": "Nonclassical nicotine antagonists.", "content": "A series of \"nonclassical\" nicotine antagonists was synthesized and compared to the \"classical\" nicotine antagonist, hexamethonium, by means of the isolated guinea pig atria preparation. 2 was found to be the most potent, followed by hexamethonium and the other antagonists. With the exception of 5, the bisquaternary compounds 1-3 and 7-9 were found to be more potent than the monoquaternary compounds 4, 6, and 10-12. Within a series of compounds (1-6 or 7-12), those compounds possessing two phenyl rings proved to be more potent than those possessing one or three phenyl rings. These and other aspects of the structure-activity relationship of this class of compounds are discussed.", "contents": "Nonclassical nicotine antagonists. A series of \"nonclassical\" nicotine antagonists was synthesized and compared to the \"classical\" nicotine antagonist, hexamethonium, by means of the isolated guinea pig atria preparation. 2 was found to be the most potent, followed by hexamethonium and the other antagonists. With the exception of 5, the bisquaternary compounds 1-3 and 7-9 were found to be more potent than the monoquaternary compounds 4, 6, and 10-12. Within a series of compounds (1-6 or 7-12), those compounds possessing two phenyl rings proved to be more potent than those possessing one or three phenyl rings. These and other aspects of the structure-activity relationship of this class of compounds are discussed."}
{"id": "PMID:240940", "title": "Synthesis and antibacterial properties of methylsulfinyl and methylsulfonyl analongs of some nitrofurans.", "content": "The sulfoxides 5-methylsulfinyl-2-furaldehyde semicarbazone (2) and 1-[(5-methylsulfinyl-2-fufurylidene)amino]hydantoin (3) as well as the sulfones 1-[(5-methylsulfonyl-2-furfurylidene)animo]hydantoin (1) and 1-(5-methylsulfonly-2-furyl)-2-(6-amino-3-p-ridazyl)ethylene hydrochloride (4) have been prepared and tested for antibacterial activity against a number of gram-negative and gram-positive organisms. The compounds are much less active than the corresponding 5-nitrofuran derivatives, possibly because their reduction potentials are too negative for them to interfere with reductive enzyme systems within the bacteria.", "contents": "Synthesis and antibacterial properties of methylsulfinyl and methylsulfonyl analongs of some nitrofurans. The sulfoxides 5-methylsulfinyl-2-furaldehyde semicarbazone (2) and 1-[(5-methylsulfinyl-2-fufurylidene)amino]hydantoin (3) as well as the sulfones 1-[(5-methylsulfonyl-2-furfurylidene)animo]hydantoin (1) and 1-(5-methylsulfonly-2-furyl)-2-(6-amino-3-p-ridazyl)ethylene hydrochloride (4) have been prepared and tested for antibacterial activity against a number of gram-negative and gram-positive organisms. The compounds are much less active than the corresponding 5-nitrofuran derivatives, possibly because their reduction potentials are too negative for them to interfere with reductive enzyme systems within the bacteria."}
{"id": "PMID:240941", "title": "Complement-dependent and complement-independent interactions between Mycoplasma hominis and antibodies in vitro.", "content": "Several in vitro reactions between a strain of M. hominis (no. 4195) and homologous antiserum have been delineated and compared. One complement-dependent and four complement-independent activities of antibody have been studied. The complement-dependent activity was mycoplasmacidal and was inhibited by the presence of arginine in the test medium. The complement-independent antibody-mediated reactions were not mycoplasmacidal and were four in number: (a) agglutination, which was manifested in buffered saline after incubation for 24-48 h at 36 degrees C, and in which the end-points were dependent upon the concentration of antigen; (b) metabolic inhibition, in which antiserum added to liquid growth medium produced slowing of the rate at which the pH rises during growth; (c) agglutination during growth, which occurred in liquid growth medium after the addition of antiserum and coincided with, but generally preceded, metabolic inhibition; and (d) inhibition of multiplication in which high concentrations of antiserum led to inhibition of multiplication or metabolic activity, with persistence of viable mycoplasmas, under otherwise favourable conditions of growth. The end-points for each of the above methods of detecting antibody are not identical.", "contents": "Complement-dependent and complement-independent interactions between Mycoplasma hominis and antibodies in vitro. Several in vitro reactions between a strain of M. hominis (no. 4195) and homologous antiserum have been delineated and compared. One complement-dependent and four complement-independent activities of antibody have been studied. The complement-dependent activity was mycoplasmacidal and was inhibited by the presence of arginine in the test medium. The complement-independent antibody-mediated reactions were not mycoplasmacidal and were four in number: (a) agglutination, which was manifested in buffered saline after incubation for 24-48 h at 36 degrees C, and in which the end-points were dependent upon the concentration of antigen; (b) metabolic inhibition, in which antiserum added to liquid growth medium produced slowing of the rate at which the pH rises during growth; (c) agglutination during growth, which occurred in liquid growth medium after the addition of antiserum and coincided with, but generally preceded, metabolic inhibition; and (d) inhibition of multiplication in which high concentrations of antiserum led to inhibition of multiplication or metabolic activity, with persistence of viable mycoplasmas, under otherwise favourable conditions of growth. The end-points for each of the above methods of detecting antibody are not identical."}
{"id": "PMID:240948", "title": "Cephalexin monohydrate suspension. Treatment of otitis media.", "content": "Cephalexin monohydrate suspension was used in the treatment of 97 children with otitis media. Pretreatment middle-ear exudate specimens in pure or mixed culture yielded Diplococcus pneumoniae in 47 cases, Haemophilus influenzae in 26, Neisseria catarrhalis in 20, group A beta-hemolytic streptococci in 13, and Staphylococcus aureus in one. The usual dosage was 100 mg/kg/day given orally in divided doses for 10 to 12 days. After 48 hours of treatment, follow-up cultures showed that therapy had been successful in 90 children; 81 remained clinically and bacteriologically free of disease for at least three weeks following therapy. Of the seven children for whom therapy failed, H influenzae persisted in five and D pneumoniae in two. Acceptance of the drug was entirely satisfactory with no important side effects encountered.", "contents": "Cephalexin monohydrate suspension. Treatment of otitis media. Cephalexin monohydrate suspension was used in the treatment of 97 children with otitis media. Pretreatment middle-ear exudate specimens in pure or mixed culture yielded Diplococcus pneumoniae in 47 cases, Haemophilus influenzae in 26, Neisseria catarrhalis in 20, group A beta-hemolytic streptococci in 13, and Staphylococcus aureus in one. The usual dosage was 100 mg/kg/day given orally in divided doses for 10 to 12 days. After 48 hours of treatment, follow-up cultures showed that therapy had been successful in 90 children; 81 remained clinically and bacteriologically free of disease for at least three weeks following therapy. Of the seven children for whom therapy failed, H influenzae persisted in five and D pneumoniae in two. Acceptance of the drug was entirely satisfactory with no important side effects encountered."}
{"id": "PMID:240949", "title": "Employment of MEDEX graduates and trainees. Five-year progress report for the United States.", "content": "The MEDEX approach to the training and deployment of physician extenders is described and contrasted with other physician-extender training models, and results of a survey of 277 MEDEX graduates and 207 trainees are presented. Practically all MEDEX graduates and trainees are employed in full-time practice and are working with fee-for-service family physicians in the rural areas of the United States, which suggests that the strategy used to place Medex practitioners into communities requiring additional health services has been successful.", "contents": "Employment of MEDEX graduates and trainees. Five-year progress report for the United States. The MEDEX approach to the training and deployment of physician extenders is described and contrasted with other physician-extender training models, and results of a survey of 277 MEDEX graduates and 207 trainees are presented. Practically all MEDEX graduates and trainees are employed in full-time practice and are working with fee-for-service family physicians in the rural areas of the United States, which suggests that the strategy used to place Medex practitioners into communities requiring additional health services has been successful."}
{"id": "PMID:240951", "title": "Juvenile temporal arteritis. Biopsy study of four cases.", "content": "Two young adults (aged 21 and 22 years) and two children (aged 7 and 8 years) complained of an unsightly, soft, painless unilateral nodule in the temporal region, ranging from 0.5 to 1.5 cm in diameter, clinically diagnosed as lipoma, sebaceous cyst, or dermoid cyst. In each instance, the patient had no evidence of systemic disease or history of trauma, and the nodule was excised for cosmetic reasons. Histologic examination of the lesions showed non-giant-cell granulomatous inflammation of the temporal arteries with intimal proliferation and microaneurysmal disruption of the media. Whether the lesions represent a juvenile form of temporal arteritis, an unusual form of localized polyarteritis nodosa, or Kimura disease (subcutaneous angiolymphoid hyperplasia with eosinophilia) remains conjectural.", "contents": "Juvenile temporal arteritis. Biopsy study of four cases. Two young adults (aged 21 and 22 years) and two children (aged 7 and 8 years) complained of an unsightly, soft, painless unilateral nodule in the temporal region, ranging from 0.5 to 1.5 cm in diameter, clinically diagnosed as lipoma, sebaceous cyst, or dermoid cyst. In each instance, the patient had no evidence of systemic disease or history of trauma, and the nodule was excised for cosmetic reasons. Histologic examination of the lesions showed non-giant-cell granulomatous inflammation of the temporal arteries with intimal proliferation and microaneurysmal disruption of the media. Whether the lesions represent a juvenile form of temporal arteritis, an unusual form of localized polyarteritis nodosa, or Kimura disease (subcutaneous angiolymphoid hyperplasia with eosinophilia) remains conjectural."}
{"id": "PMID:240955", "title": "[Agar tube method for the bioassay of antibiotics (author's transl)].", "content": "A simplified bioassay system for antibiotics has been presented. Glass tubes with open ends and pits are filled with agar medium containing test microbes by immersing vertically into the agar medium while it is warm. These agar tubes are inserted in test solutions and incubated. The growth-inhibitory zones appear in respective tubes due to upward diffusion of the antibiotic. The heights of such zones from the bottom of agar tubes are measured.", "contents": "[Agar tube method for the bioassay of antibiotics (author's transl)]. A simplified bioassay system for antibiotics has been presented. Glass tubes with open ends and pits are filled with agar medium containing test microbes by immersing vertically into the agar medium while it is warm. These agar tubes are inserted in test solutions and incubated. The growth-inhibitory zones appear in respective tubes due to upward diffusion of the antibiotic. The heights of such zones from the bottom of agar tubes are measured."}
{"id": "PMID:240959", "title": "An alpha adrenergic mechanism in the ascending reticular activating system.", "content": "The effect of electrical stimulation of the mesencephalic reticular formation (MRF) on the pyramidal tract (PT) response to cortical stimulation in adult rats was examined with and without alpha adrenergic blocking agents and other chemicals, applied intravenously, intraperitoneally or topically to the exposed cerebral cortex. 1. By MRF stimulation, the initial component of the PT response (D wave) was not significantly altered but the later component (I waves) was initially facilitated and subsequently inhibited. 2. Intravenously applied alpha adrenergic blocking agents, phentolamine and phenoxybenzamine consistently blocked reticulo-cortical inhibition. The reticulo-cortical facilitation was significantly reduced by phentolamine but the effect of phenoxybenazmine was not consistent on this mechanism. Neither the PT response nor the effect of MRF stimulation on it was affected by propranolol or atropine. 3. Phentolamine or phenoxybenazmine, topically applied to the cortical surface, blocked the reticulo-cortical inhibition but did not alter the reticulo-cortical facilitation. 4. A monoamine oxidase inhibitor, iproniazid (i.p.), significantly potentiated the reticulo-cortical inhibition but the effect on the reticulocortical facilitation was not statistically significant. 5. These results suggest that the reticular inhibitory effect on the motor cortical activity is mediated through an alpha adrenergic mechanism and the receptor site is distributed in the cerebral cortex.", "contents": "An alpha adrenergic mechanism in the ascending reticular activating system. The effect of electrical stimulation of the mesencephalic reticular formation (MRF) on the pyramidal tract (PT) response to cortical stimulation in adult rats was examined with and without alpha adrenergic blocking agents and other chemicals, applied intravenously, intraperitoneally or topically to the exposed cerebral cortex. 1. By MRF stimulation, the initial component of the PT response (D wave) was not significantly altered but the later component (I waves) was initially facilitated and subsequently inhibited. 2. Intravenously applied alpha adrenergic blocking agents, phentolamine and phenoxybenzamine consistently blocked reticulo-cortical inhibition. The reticulo-cortical facilitation was significantly reduced by phentolamine but the effect of phenoxybenazmine was not consistent on this mechanism. Neither the PT response nor the effect of MRF stimulation on it was affected by propranolol or atropine. 3. Phentolamine or phenoxybenazmine, topically applied to the cortical surface, blocked the reticulo-cortical inhibition but did not alter the reticulo-cortical facilitation. 4. A monoamine oxidase inhibitor, iproniazid (i.p.), significantly potentiated the reticulo-cortical inhibition but the effect on the reticulocortical facilitation was not statistically significant. 5. These results suggest that the reticular inhibitory effect on the motor cortical activity is mediated through an alpha adrenergic mechanism and the receptor site is distributed in the cerebral cortex."}
{"id": "PMID:240960", "title": "[Fat-emulsions and acid-base balance in neonates of low weight at birth (author's transl)].", "content": "The influence of a single intravenous infusion of triglycerides (1 g triglyceride per kg body weight) on the acid base equilibrium was investigated in 16 newborn infants with low birth weight during the first days of age. No changes of pH, PCO2 and standard bicarbonate, base excess, buffer base and actuelle bicarbonate, respectively, were observed. Fat emulsions can be used, therefore, without hazards in the parenteral feeding of newborn infants.", "contents": "[Fat-emulsions and acid-base balance in neonates of low weight at birth (author's transl)]. The influence of a single intravenous infusion of triglycerides (1 g triglyceride per kg body weight) on the acid base equilibrium was investigated in 16 newborn infants with low birth weight during the first days of age. No changes of pH, PCO2 and standard bicarbonate, base excess, buffer base and actuelle bicarbonate, respectively, were observed. Fat emulsions can be used, therefore, without hazards in the parenteral feeding of newborn infants."}
{"id": "PMID:240962", "title": "[A method for quantitative dertermination of 20-keto steroids in urine during the use of a 3 alpha-, 20 beta-hydroxysteroid: NAD oxidoreductase (author's transl)].", "content": "A method is described for the quantitative determination of 20-ketosteroids in urine during the application of a 3alpha, 20beta-hydroxysteroid: NAD oxidoreductase. In the presence of NADH H+ the enzyme catalyses in an \"equimolar\" developing reaction the reduction of 20-keto groups of C-21 steroids giving 20 beta-alcohols. The measurable NADH H+ consumption is a measure for the quantity of those 20-ketosteroids present in the reaction mixture. The 3alpha-hydroxysteroid: NAD oxidoreductase activity of the enzyme does not influence the specificity of the method to determine the 20-ketosteroids because,-under the present extraction and purification conditions-those 3alpha-hydroxy-5alpha-androstan derivatives are not reaching the reaction mixture of determination. The demands towards the criterions of reliability (correctness and exactitude) come to be fulfilled by this method.", "contents": "[A method for quantitative dertermination of 20-keto steroids in urine during the use of a 3 alpha-, 20 beta-hydroxysteroid: NAD oxidoreductase (author's transl)]. A method is described for the quantitative determination of 20-ketosteroids in urine during the application of a 3alpha, 20beta-hydroxysteroid: NAD oxidoreductase. In the presence of NADH H+ the enzyme catalyses in an \"equimolar\" developing reaction the reduction of 20-keto groups of C-21 steroids giving 20 beta-alcohols. The measurable NADH H+ consumption is a measure for the quantity of those 20-ketosteroids present in the reaction mixture. The 3alpha-hydroxysteroid: NAD oxidoreductase activity of the enzyme does not influence the specificity of the method to determine the 20-ketosteroids because,-under the present extraction and purification conditions-those 3alpha-hydroxy-5alpha-androstan derivatives are not reaching the reaction mixture of determination. The demands towards the criterions of reliability (correctness and exactitude) come to be fulfilled by this method."}
{"id": "PMID:240961", "title": "[The role of cyclic adenosine 3':5'-monophosphate as \"second messenger\" in gastric acids secretion (author's transl)].", "content": "The criteria to determine whether cyclic adenosine 3':5'-monophosphate (cyclic AMP) is or is not involved in a particular hormone response require to look for positive qualitive, quantitative and temporal correlations between the effects of the hormone on cyclic AMP levels and the physiological response. These requirements have been shown to be fulfilled in histamine and pentagastrin-stimulated gastric acid secretion of the frog (Necturus maculosus) and the rat. In dog and man, however, the available evidence does not support a role for cyclic AMP in the gastric secretory process; it remains a challenge for future research whether in those species cyclic guanosine 3':5'-monophosphate acts as an intracellular substitute for cyclic AMP.", "contents": "[The role of cyclic adenosine 3':5'-monophosphate as \"second messenger\" in gastric acids secretion (author's transl)]. The criteria to determine whether cyclic adenosine 3':5'-monophosphate (cyclic AMP) is or is not involved in a particular hormone response require to look for positive qualitive, quantitative and temporal correlations between the effects of the hormone on cyclic AMP levels and the physiological response. These requirements have been shown to be fulfilled in histamine and pentagastrin-stimulated gastric acid secretion of the frog (Necturus maculosus) and the rat. In dog and man, however, the available evidence does not support a role for cyclic AMP in the gastric secretory process; it remains a challenge for future research whether in those species cyclic guanosine 3':5'-monophosphate acts as an intracellular substitute for cyclic AMP."}
{"id": "PMID:240967", "title": "Changes in ethanol consumption by C3H and CF1 mice with age.", "content": "Water or a 3% alcohol solution was offered for 4 weeks to groups of male C3H mice initially aged 3, 13, 20 and 60 weeks, and to male CF1 mice from age 10 weeks until they died. Differences in the consumption depended on age and the rate at which response patterns to the solution develop.", "contents": "Changes in ethanol consumption by C3H and CF1 mice with age. Water or a 3% alcohol solution was offered for 4 weeks to groups of male C3H mice initially aged 3, 13, 20 and 60 weeks, and to male CF1 mice from age 10 weeks until they died. Differences in the consumption depended on age and the rate at which response patterns to the solution develop."}
{"id": "PMID:240968", "title": "Voluntary consumption of alcohol by baboons. Effects of flavor, concentration and temperature of solution.", "content": "Nonrestrained, group-housed baboons drank the greatest amounts of alcohol when it was presented as a 10% to 20% solution in cold fruit juice.", "contents": "Voluntary consumption of alcohol by baboons. Effects of flavor, concentration and temperature of solution. Nonrestrained, group-housed baboons drank the greatest amounts of alcohol when it was presented as a 10% to 20% solution in cold fruit juice."}
{"id": "PMID:240969", "title": "Effects of long-term administration of alcoholic beverages on the kidney, heart, skeletal muscle and pancreas of rats. A histological study.", "content": "No pathological changes in the pancreas, kidneys or skeletal muscle were found in rats maintained for 8 to 9 months with a diet in which alcohol made up 50% of the total calories. An increase of the dietary fat content to 38% did not cause any fatty infiltration of the myocardium.", "contents": "Effects of long-term administration of alcoholic beverages on the kidney, heart, skeletal muscle and pancreas of rats. A histological study. No pathological changes in the pancreas, kidneys or skeletal muscle were found in rats maintained for 8 to 9 months with a diet in which alcohol made up 50% of the total calories. An increase of the dietary fat content to 38% did not cause any fatty infiltration of the myocardium."}
{"id": "PMID:240970", "title": "Social control of drinking among the Aztec Indians of Mesoamerica.", "content": "In the Aztec culture of pre-Columbian Mexico the rules for the use of alcoholic beverages were clearly defined and strictly enforced. Drinking was permitted only on religious occasions and the amount drunk was restricted.", "contents": "Social control of drinking among the Aztec Indians of Mesoamerica. In the Aztec culture of pre-Columbian Mexico the rules for the use of alcoholic beverages were clearly defined and strictly enforced. Drinking was permitted only on religious occasions and the amount drunk was restricted."}
{"id": "PMID:240971", "title": "Measurement and interpretation of drinking behavior. I. On measuring patterns of alcohol consumption. II. Relationships between drinking behavior and social adjustment in a sample of problem drinkers.", "content": "Different systems for measuring drinking behavior were reviewed and compared. A revised system based on volume and pattern was devised, and its utility in predicting social adjustment was tested.", "contents": "Measurement and interpretation of drinking behavior. I. On measuring patterns of alcohol consumption. II. Relationships between drinking behavior and social adjustment in a sample of problem drinkers. Different systems for measuring drinking behavior were reviewed and compared. A revised system based on volume and pattern was devised, and its utility in predicting social adjustment was tested."}
{"id": "PMID:240972", "title": "Situations related to drinking alcohol. A factor analysis of questionnaire responses.", "content": "Problem and nonproblem drinkers indicated on a questionnaire the degree to which they used alcohol in certain situations. The responses were factor analyzed and seven factor scales were developed. It is suggested that the questionnaire could be used as an initial diagnostic step leading to specific treatment alternatives.", "contents": "Situations related to drinking alcohol. A factor analysis of questionnaire responses. Problem and nonproblem drinkers indicated on a questionnaire the degree to which they used alcohol in certain situations. The responses were factor analyzed and seven factor scales were developed. It is suggested that the questionnaire could be used as an initial diagnostic step leading to specific treatment alternatives."}
{"id": "PMID:240973", "title": "The predisposition toward alcohol-related interpersonal aggression in men.", "content": "Men social drinkers participated in experimental \"parties' which were videotaped and coded for instances of interpersonal aggression. Participants with a history of arguments and other aggressive acts and low scores on measures of socialization, self-control and responsibility demonstrated interpersonal aggression after heavy drinking.", "contents": "The predisposition toward alcohol-related interpersonal aggression in men. Men social drinkers participated in experimental \"parties' which were videotaped and coded for instances of interpersonal aggression. Participants with a history of arguments and other aggressive acts and low scores on measures of socialization, self-control and responsibility demonstrated interpersonal aggression after heavy drinking."}
{"id": "PMID:240974", "title": "Collision behavior of young drivers. Impact of the change in the age of majority.", "content": "A comparison of the number of collisions experienced by young male drivers in London, Ontario, before and after the reduction in the legal age for drinking and purchasing alcoholic beverages from 21 to 18, indicated that the change in the law led to an increase in the collision involvement of young drivers.", "contents": "Collision behavior of young drivers. Impact of the change in the age of majority. A comparison of the number of collisions experienced by young male drivers in London, Ontario, before and after the reduction in the legal age for drinking and purchasing alcoholic beverages from 21 to 18, indicated that the change in the law led to an increase in the collision involvement of young drivers."}
{"id": "PMID:240975", "title": "Death in young alcoholics.", "content": "Homicide, accidents and heart disease were the leading causes of death among young alcoholics treated at an outpatient alcoholism clinic over a 3-year period. Ways of preventing early death in alcoholics are suggested.", "contents": "Death in young alcoholics. Homicide, accidents and heart disease were the leading causes of death among young alcoholics treated at an outpatient alcoholism clinic over a 3-year period. Ways of preventing early death in alcoholics are suggested."}
{"id": "PMID:240976", "title": "Use of the MMPI in predicting completion and evaluating changes in a long-term alcoholism treatment program.", "content": "Veterans admitted to a 90-day alcoholism treatment program were administered the MMPI, and those who completed the program were retested before discharge. Completers differed significantly from noncompleters on the Pd scale. Although responses on most MMPI scales indicated improvement after treatment, those on the MacAndrew Alcoholism Scale were not affected. Neither the MacAndrew nor the Unitary Alcoholism Factor differentiated between completers and noncompleters.", "contents": "Use of the MMPI in predicting completion and evaluating changes in a long-term alcoholism treatment program. Veterans admitted to a 90-day alcoholism treatment program were administered the MMPI, and those who completed the program were retested before discharge. Completers differed significantly from noncompleters on the Pd scale. Although responses on most MMPI scales indicated improvement after treatment, those on the MacAndrew Alcoholism Scale were not affected. Neither the MacAndrew nor the Unitary Alcoholism Factor differentiated between completers and noncompleters."}
{"id": "PMID:240977", "title": "Changes in construing and outcome of group therapy for alcoholism.", "content": "Consistent changes in the way they construed their drinking problem were found in alcoholics who completed an inpatient group therapy program. Patients who showed most change in construal were the ones most likely to relapse.", "contents": "Changes in construing and outcome of group therapy for alcoholism. Consistent changes in the way they construed their drinking problem were found in alcoholics who completed an inpatient group therapy program. Patients who showed most change in construal were the ones most likely to relapse."}
{"id": "PMID:240978", "title": "Self-reported coping behavior of wives of alcoholics and its association with drinking outcome.", "content": "The frequency of the use of coping behavior by wives of alcoholics was found to be related to their husband's drinking outcome. In general, a high frequency of coping behavior was associated with a poor outcome, but some components of coping behavior were more likely than others to be linked with a poor prognosis.", "contents": "Self-reported coping behavior of wives of alcoholics and its association with drinking outcome. The frequency of the use of coping behavior by wives of alcoholics was found to be related to their husband's drinking outcome. In general, a high frequency of coping behavior was associated with a poor outcome, but some components of coping behavior were more likely than others to be linked with a poor prognosis."}
{"id": "PMID:240979", "title": "Effects of discontinuity of medication on the results of a double-blind drug study in outpatient alcoholics.", "content": "When the analysis of results of a double-blind drug study included outpatient alcoholics who missed clinic visits no differences were found between drug and placebo groups. When only patients who took adequate levels of medication were considered, the drug group fared significantly better than the placebo group.", "contents": "Effects of discontinuity of medication on the results of a double-blind drug study in outpatient alcoholics. When the analysis of results of a double-blind drug study included outpatient alcoholics who missed clinic visits no differences were found between drug and placebo groups. When only patients who took adequate levels of medication were considered, the drug group fared significantly better than the placebo group."}
{"id": "PMID:240980", "title": "Effects of crowding on alcohol consumption by rats.", "content": "Rats housed eight to a cage consumed significantly more 10% ethanol mixed with milk than did rats housed individually.", "contents": "Effects of crowding on alcohol consumption by rats. Rats housed eight to a cage consumed significantly more 10% ethanol mixed with milk than did rats housed individually."}
{"id": "PMID:240981", "title": "Comparison of outcome in a 9-day and 30-day alcoholism treatment program.", "content": "At 3 and 6 months after discharge no differences in abstinence rates were found between patients who completed a 9-day inpatient alcoholism treatment program and those who participated in a 21-day treatment program.", "contents": "Comparison of outcome in a 9-day and 30-day alcoholism treatment program. At 3 and 6 months after discharge no differences in abstinence rates were found between patients who completed a 9-day inpatient alcoholism treatment program and those who participated in a 21-day treatment program."}
{"id": "PMID:240982", "title": "Evidence that revascularization by ventricular-internal mammary artery implants increases longevity. Twenty-four year, nine month follow-up.", "content": "Revascularization of the heart is a means of relieving symptoms of coronary artery disease--such as angina, fatigue, and dyspnea. The question of whether revascularization prolongs the life of the patient has been debated. My colleagues and I have reviewed our years of experience with patients treated by implantation of internal mammary arteries into the ventricles. We have compared our series with other groups of patients treated medically. Our conclusion is that revascularization via internal mammary artery implants does increase longevity.", "contents": "Evidence that revascularization by ventricular-internal mammary artery implants increases longevity. Twenty-four year, nine month follow-up. Revascularization of the heart is a means of relieving symptoms of coronary artery disease--such as angina, fatigue, and dyspnea. The question of whether revascularization prolongs the life of the patient has been debated. My colleagues and I have reviewed our years of experience with patients treated by implantation of internal mammary arteries into the ventricles. We have compared our series with other groups of patients treated medically. Our conclusion is that revascularization via internal mammary artery implants does increase longevity."}
{"id": "PMID:240983", "title": "Myocardial scintigraphy. Post-Vineberg study.", "content": "In order to assess myocardial perfusion of Vineberg implants, tracer particles (99mCc and 131I-MAA) were injected into the internal mammary implants of 7 patients (6 years after the operation) after selective contrast visualization. The myocardial perfusion images were correlated with the internal mammary arteriographic findings. Of those patients with patent implants with communication, the myocardial scintigrams demonstrated even distribution of radioactive particles reflecting myocardial perfusion at the capillary or precapillary bed.", "contents": "Myocardial scintigraphy. Post-Vineberg study. In order to assess myocardial perfusion of Vineberg implants, tracer particles (99mCc and 131I-MAA) were injected into the internal mammary implants of 7 patients (6 years after the operation) after selective contrast visualization. The myocardial perfusion images were correlated with the internal mammary arteriographic findings. Of those patients with patent implants with communication, the myocardial scintigrams demonstrated even distribution of radioactive particles reflecting myocardial perfusion at the capillary or precapillary bed."}
{"id": "PMID:240984", "title": "Selection of coronary bypass. Anatomic, physiological, and angiographic considerations of vein and mammary artery grafts.", "content": "Results of direct coronary revascularization with 511 grafts in 213 patients from 1971 to 1974 are reviewed. To improve an early saphenous vein graft (SVG) patency of 84 per cent in the first 85 patients, we have used internal mammary artery grafts (IMAG), when possible, since January, 1973. In 1973 to 1974, 15 patients had SVG's only (36 grafts) and 113 received one or two IMAG's with or without additional SVG's (total 282 grafts); in 26 we used a crossed double IMAG. Forty-seven of 48 patients with unstable angina survived and did well. Flows in SVG's and IMAG's were comparable. Flows in right IMAG's to diagonal or marginal vessels were higher than in right IMAG's to right or left anterior descending (LAD) vessels. In 12 patients with both SVG and IMAG, there was no difference in flow response of either graft to vasoactive drugs. Survival, functional, and patency results with IMAG's were as good as or better than results with SVG's. We conclude that IMAG's yield higher patency and comparable flow rates to SVG's and should be used when the IMA approximates the recipient artery in size and when a high pulsatile free flow is measured from the end of the graft. IMAG's are also safe and feasible for unstable angina.", "contents": "Selection of coronary bypass. Anatomic, physiological, and angiographic considerations of vein and mammary artery grafts. Results of direct coronary revascularization with 511 grafts in 213 patients from 1971 to 1974 are reviewed. To improve an early saphenous vein graft (SVG) patency of 84 per cent in the first 85 patients, we have used internal mammary artery grafts (IMAG), when possible, since January, 1973. In 1973 to 1974, 15 patients had SVG's only (36 grafts) and 113 received one or two IMAG's with or without additional SVG's (total 282 grafts); in 26 we used a crossed double IMAG. Forty-seven of 48 patients with unstable angina survived and did well. Flows in SVG's and IMAG's were comparable. Flows in right IMAG's to diagonal or marginal vessels were higher than in right IMAG's to right or left anterior descending (LAD) vessels. In 12 patients with both SVG and IMAG, there was no difference in flow response of either graft to vasoactive drugs. Survival, functional, and patency results with IMAG's were as good as or better than results with SVG's. We conclude that IMAG's yield higher patency and comparable flow rates to SVG's and should be used when the IMA approximates the recipient artery in size and when a high pulsatile free flow is measured from the end of the graft. IMAG's are also safe and feasible for unstable angina."}
{"id": "PMID:240985", "title": "Myocardial injury and bypass grafting. Value of serum enzymes in diagnosis.", "content": "To clarify the value of serum enzymes in the detection of intraoperative and postoperative myocardial injury associated with coronary artery bypass grafting, we evaluated 70 consecutive patients (151 grafts). We used electrocardiograms and serial determinations of serum levels: serum glutamic oxaloacetic transaminase (SGOT), creatinine phosphokinase (CPK), lactic dehydrogenase (LDH), and LDH isoenzymes on Days zero, 1, 3, 5, 7, and 10. Patency of all grafts 1 week postoperatively was 92 per cent. Fourteen patients (20 per cent) had ECG evidence of acute myocardial infarction (AMI) or ischemia lasting longer than 48 hours. This incidence of AMI was attendant with no deaths or discernible changes in postoperative ventriculography. LDH-1 (cardiac fraction) was elevated in all patients with myocardial injury. Late elevation of LDH-1 occurred in 2 patients at the time of postoperative catheterization, 1 of whom had negative findings on ECG. Diagnostic correlation was not observed with total LDH, CPK, or SGOT. Predisposing factors to AMI included preinfarction angina (4 of 14 patients), occluded grafts (4 of 14), and a bypass time greater than 120 minutes.", "contents": "Myocardial injury and bypass grafting. Value of serum enzymes in diagnosis. To clarify the value of serum enzymes in the detection of intraoperative and postoperative myocardial injury associated with coronary artery bypass grafting, we evaluated 70 consecutive patients (151 grafts). We used electrocardiograms and serial determinations of serum levels: serum glutamic oxaloacetic transaminase (SGOT), creatinine phosphokinase (CPK), lactic dehydrogenase (LDH), and LDH isoenzymes on Days zero, 1, 3, 5, 7, and 10. Patency of all grafts 1 week postoperatively was 92 per cent. Fourteen patients (20 per cent) had ECG evidence of acute myocardial infarction (AMI) or ischemia lasting longer than 48 hours. This incidence of AMI was attendant with no deaths or discernible changes in postoperative ventriculography. LDH-1 (cardiac fraction) was elevated in all patients with myocardial injury. Late elevation of LDH-1 occurred in 2 patients at the time of postoperative catheterization, 1 of whom had negative findings on ECG. Diagnostic correlation was not observed with total LDH, CPK, or SGOT. Predisposing factors to AMI included preinfarction angina (4 of 14 patients), occluded grafts (4 of 14), and a bypass time greater than 120 minutes."}
{"id": "PMID:240986", "title": "Manual coronary endarterectomy. Clinical experience in 315 patients.", "content": "From July, 1970, to December, 1973, manual endarterectomies were performed on 330 coronary arteries in 315 patients. The procedures were performed on either an elective or nonelective basis. The over-all hospital mortality rate was 1.27 per cent. Postoperative myocardial infarction occurred in 4.8 per cent of these patients. Postoperative catheterization was performed on 186 endarterectomized arteries; the average time of postoperative catheterization was 13.1 months after surgery. The over-all patency rate was 76.3 per cent. This experience suggests that endarterectomy is a safe and useful adjunct to saphenous vein bypass grafting procedures when used in a restricted fashion as detailed in this presentation.", "contents": "Manual coronary endarterectomy. Clinical experience in 315 patients. From July, 1970, to December, 1973, manual endarterectomies were performed on 330 coronary arteries in 315 patients. The procedures were performed on either an elective or nonelective basis. The over-all hospital mortality rate was 1.27 per cent. Postoperative myocardial infarction occurred in 4.8 per cent of these patients. Postoperative catheterization was performed on 186 endarterectomized arteries; the average time of postoperative catheterization was 13.1 months after surgery. The over-all patency rate was 76.3 per cent. This experience suggests that endarterectomy is a safe and useful adjunct to saphenous vein bypass grafting procedures when used in a restricted fashion as detailed in this presentation."}
{"id": "PMID:240987", "title": "Helix-coil stability constants for the naturally occurring amino acids in water. IX. Glutamic acid parameters from random poly(hydroxybutylglutamine-co-L-glutamic acid).", "content": "The synthesis and characterization of water-soluble random copolymers containing L-glutamic acid with N5-(4-hydroxybutyl)-L-glutamine and the thermally induced helix-coil transitions of these copolymers in water and in 0.1 N KCl are described. The incorporation of L-glutamic acid was found to increase the helix content of the polymer at low pH and to decrease it at high pH even though the presence of 0.1 N KCl effectively eliminated the difference between the electrostatic free energies of the helix and the coil. The Zimm-Bragg parameters sigma and s for the helix-coil transition in poly(L-glutamic acid) in water and in 0.1 N KCl were deduced from an analysis of the melting curves of the copolymers in the manner described in earlier papers. The synthesis of N-acetyl-N'-methylglutamic acid amide and its titration, as well as that of the copolymers and poly(L-glutamic acid), in 0.1 N KCl are described.", "contents": "Helix-coil stability constants for the naturally occurring amino acids in water. IX. Glutamic acid parameters from random poly(hydroxybutylglutamine-co-L-glutamic acid). The synthesis and characterization of water-soluble random copolymers containing L-glutamic acid with N5-(4-hydroxybutyl)-L-glutamine and the thermally induced helix-coil transitions of these copolymers in water and in 0.1 N KCl are described. The incorporation of L-glutamic acid was found to increase the helix content of the polymer at low pH and to decrease it at high pH even though the presence of 0.1 N KCl effectively eliminated the difference between the electrostatic free energies of the helix and the coil. The Zimm-Bragg parameters sigma and s for the helix-coil transition in poly(L-glutamic acid) in water and in 0.1 N KCl were deduced from an analysis of the melting curves of the copolymers in the manner described in earlier papers. The synthesis of N-acetyl-N'-methylglutamic acid amide and its titration, as well as that of the copolymers and poly(L-glutamic acid), in 0.1 N KCl are described."}
{"id": "PMID:241001", "title": "[Role of ferredoxin in the metabolism of hydrogen by Rhodospirillum rubrum].", "content": "Ferredoxin was purified after isolation from the cells of Rhodospirillum rubrum grown under photoheterotrophic conditions; A385/A280 in the absorption spectrum was not less than 0.53; the molecular weight was ca. 7700; E0' (pH 7.0)--430 mv. Ferredoxin was easily reduced in the presence of dithionite and provided a high rate of NADP reduction by pea chloroplasts. The extracts of R. rubrum containing ferredoxin or the extracts, to which it was added, reduced NAD in the presence of hydrogen and evolved H2 in the presence of NAD(P)H. ATP or light were required for the evolution of H2 from NAD(P)H.", "contents": "[Role of ferredoxin in the metabolism of hydrogen by Rhodospirillum rubrum]. Ferredoxin was purified after isolation from the cells of Rhodospirillum rubrum grown under photoheterotrophic conditions; A385/A280 in the absorption spectrum was not less than 0.53; the molecular weight was ca. 7700; E0' (pH 7.0)--430 mv. Ferredoxin was easily reduced in the presence of dithionite and provided a high rate of NADP reduction by pea chloroplasts. The extracts of R. rubrum containing ferredoxin or the extracts, to which it was added, reduced NAD in the presence of hydrogen and evolved H2 in the presence of NAD(P)H. ATP or light were required for the evolution of H2 from NAD(P)H."}
{"id": "PMID:241006", "title": "[Oral administration of an acidiferous drug and its effect on carbohydrate metabolism of maturity-onset-diabetics treated by oral hypoglycaemic agents].", "content": "Subacidity or anacidity may lower glucose-tolerance in elder diabetics. 65 Patients, who showed not sufficient effect of oral hypoglycaemic agents, got an acidiferous drug. Diabetes could be ameliorated significantly. Some results are contrary to itself. In 8 patients our hypothesis came true in all points. Further investigations are necessary.", "contents": "[Oral administration of an acidiferous drug and its effect on carbohydrate metabolism of maturity-onset-diabetics treated by oral hypoglycaemic agents]. Subacidity or anacidity may lower glucose-tolerance in elder diabetics. 65 Patients, who showed not sufficient effect of oral hypoglycaemic agents, got an acidiferous drug. Diabetes could be ameliorated significantly. Some results are contrary to itself. In 8 patients our hypothesis came true in all points. Further investigations are necessary."}
{"id": "PMID:241002", "title": "[Distribution of pyrimidine blocks in the DNA of Brevibacterium linens, Arthrobacter globiformis, Nocardia corallina and Nocardia rubra].", "content": "The nucleotide composition and the frequency of pyrimidine blocks were studied in DNA of the following bacteria: Brevibacterium linens (Weignamm, 1910) Breed, 1953; Arthrobacter globiformis (Conn, 1928) Conn et Dimmick, 1947; Nocardia corallina (Bergey et al., 1923) Waksman et Henrici, 1948; Nocardia rubra (Krassilnikov, 1949) Waksman et Henrici, 1948. These organisms are classed by some microbiologists as mycobacteria (the Mycobacteriaceae family) while other authors regard them as representatives of three families belonging to two orders. About 60 percent of all pyrimidines in DNA of these bacteria are found in the sequences pur-pyr-pur and pur-pyr-pyr-pur, the number of dipyrimidines being higher than the amount of monopyrimidine nucleotides. The content of dipyrimidine nucleotides in DNA of Nocardia corallina and Nocardia rubra is higher (16.8 mole %) than the content of dipyrimidine blocks in DNA of Brevibacterium linens and Arthrobacter globiformis, in which the quantity of dipyrimidines is almost the same (13.9 and 14.4 mole %). A new characteristic, the selected mean value, is suggested to evaluate differences in the distribution of pyrimidines in DNA.", "contents": "[Distribution of pyrimidine blocks in the DNA of Brevibacterium linens, Arthrobacter globiformis, Nocardia corallina and Nocardia rubra]. The nucleotide composition and the frequency of pyrimidine blocks were studied in DNA of the following bacteria: Brevibacterium linens (Weignamm, 1910) Breed, 1953; Arthrobacter globiformis (Conn, 1928) Conn et Dimmick, 1947; Nocardia corallina (Bergey et al., 1923) Waksman et Henrici, 1948; Nocardia rubra (Krassilnikov, 1949) Waksman et Henrici, 1948. These organisms are classed by some microbiologists as mycobacteria (the Mycobacteriaceae family) while other authors regard them as representatives of three families belonging to two orders. About 60 percent of all pyrimidines in DNA of these bacteria are found in the sequences pur-pyr-pur and pur-pyr-pyr-pur, the number of dipyrimidines being higher than the amount of monopyrimidine nucleotides. The content of dipyrimidine nucleotides in DNA of Nocardia corallina and Nocardia rubra is higher (16.8 mole %) than the content of dipyrimidine blocks in DNA of Brevibacterium linens and Arthrobacter globiformis, in which the quantity of dipyrimidines is almost the same (13.9 and 14.4 mole %). A new characteristic, the selected mean value, is suggested to evaluate differences in the distribution of pyrimidines in DNA."}
{"id": "PMID:241003", "title": "[Ribonucleotide reductase in Propionibacterium shermani].", "content": "The cell-free extract of Propionibacterium shermanii was found to contain B12-dependent ribonucleotide reductase. The extract of the cells grown under the conditions of the inhibited synthesis of vitamin B12 reduces ribonucleotides with the participation of B12-independent enzyme. The synthesis of B12-dependent apoenzyme of ribonucleotide reductase is partially maintained under these conditions. Both enzymes reduce preferably ribonucleoside diphosphates. The reducing agent of nucleotides in vitro is lipoic acid or dithiothreitol, in the B12-dependent pathway, and NADPH and thioredoxin, in the B12-independent pathway. Only B12-independent ribonucleotide reductase requires Mg2+ ions. Vitamin B12 in the coenzyme form inhibits the activity of B12-independent enzyme.", "contents": "[Ribonucleotide reductase in Propionibacterium shermani]. The cell-free extract of Propionibacterium shermanii was found to contain B12-dependent ribonucleotide reductase. The extract of the cells grown under the conditions of the inhibited synthesis of vitamin B12 reduces ribonucleotides with the participation of B12-independent enzyme. The synthesis of B12-dependent apoenzyme of ribonucleotide reductase is partially maintained under these conditions. Both enzymes reduce preferably ribonucleoside diphosphates. The reducing agent of nucleotides in vitro is lipoic acid or dithiothreitol, in the B12-dependent pathway, and NADPH and thioredoxin, in the B12-independent pathway. Only B12-independent ribonucleotide reductase requires Mg2+ ions. Vitamin B12 in the coenzyme form inhibits the activity of B12-independent enzyme."}
{"id": "PMID:241004", "title": "[Effect of hydrogen ions on the morphology and ultrastructure of Bacillus megaterium].", "content": "The morphology and ultrastructure of the cells of Bacillus megaterium depend on the concentration of hydrogen ions in the medium which affect, first of all, the function of division. The changes induced by hydrogen ions are temporary and disappear when the cells are put under normal conditions of growth. The \"acid-resistant\" strain of Bac. megaterium remains viable at a very high concentration of hydrogen ions (pH=4.2) and, though its morphology changes drastically, no essential damages are found, i.e. the cells become adapted to new conditions. The changes are reversible.", "contents": "[Effect of hydrogen ions on the morphology and ultrastructure of Bacillus megaterium]. The morphology and ultrastructure of the cells of Bacillus megaterium depend on the concentration of hydrogen ions in the medium which affect, first of all, the function of division. The changes induced by hydrogen ions are temporary and disappear when the cells are put under normal conditions of growth. The \"acid-resistant\" strain of Bac. megaterium remains viable at a very high concentration of hydrogen ions (pH=4.2) and, though its morphology changes drastically, no essential damages are found, i.e. the cells become adapted to new conditions. The changes are reversible."}
{"id": "PMID:241010", "title": "Energy metabolism of isolated rat thymus cells.", "content": "The energy metabolism of rat thymus cells has been investigated using preparations of isolated cells obtained by mechanical treatment of whole organs. The addition of glycolytic substrates such as glucose, pyruvate and lactate stimulates the endogenous respiration of these cells by 50%. On the other hand, succinate, glutamate and malate do not produce any effect. Oligomycin (10 mug/ml) inhibits both endogenous and glucose stimulated respiration by about 40%; 2, 4-DNP (50 muM) increases by 100% glucose induced respiration. The results obtained by using mitochondrial and glycolytic inhibitors as well as aminoxyacetic acid (AOA) and following pyridine nucleotides redox changes, support the idea that in thymus cells glucose is able to induce a great enhancement of O2 consumption both by raising the level of endogenous pyruvate and feeding the mitochondrial respiratory chain with cytosolic reducing equivalents, through an active malate-aspartate shuttle. Thymus cells exhibit a high Pasteur effect (74%). Both AOA and 2,4 DNP are able to stimulate aerobic lactate accumulation by 200% and 100% respectively, indicating that either the redox or phosphate potential do influence the rate of aerobic glycolysis in isolated thymus cells. Similar experiments are also reported on other cells with well known biochemical characteristics.", "contents": "Energy metabolism of isolated rat thymus cells. The energy metabolism of rat thymus cells has been investigated using preparations of isolated cells obtained by mechanical treatment of whole organs. The addition of glycolytic substrates such as glucose, pyruvate and lactate stimulates the endogenous respiration of these cells by 50%. On the other hand, succinate, glutamate and malate do not produce any effect. Oligomycin (10 mug/ml) inhibits both endogenous and glucose stimulated respiration by about 40%; 2, 4-DNP (50 muM) increases by 100% glucose induced respiration. The results obtained by using mitochondrial and glycolytic inhibitors as well as aminoxyacetic acid (AOA) and following pyridine nucleotides redox changes, support the idea that in thymus cells glucose is able to induce a great enhancement of O2 consumption both by raising the level of endogenous pyruvate and feeding the mitochondrial respiratory chain with cytosolic reducing equivalents, through an active malate-aspartate shuttle. Thymus cells exhibit a high Pasteur effect (74%). Both AOA and 2,4 DNP are able to stimulate aerobic lactate accumulation by 200% and 100% respectively, indicating that either the redox or phosphate potential do influence the rate of aerobic glycolysis in isolated thymus cells. Similar experiments are also reported on other cells with well known biochemical characteristics."}
{"id": "PMID:241011", "title": "Fatty acid hydroxylation in rat kidney cortex microsomes.", "content": "Rat kidney microsomes have been found to catalyze the hydroxylation of medium-chained fatty acids to the omega- and (omego-1)-hydroxy derivatives. This reaction, which requires NADPH and molecular oxygen, is a function of monooxygenase system present in the kidney microsomes, containing NADPH-cytochrome c reductase and cytochrome P-450K. NADH is about half as effective as an electron donor as NADPH and there is an additive effect in the presence of both nucleotides. Cytochrome P-450K absorbs light maximally at 452-3 nm, when it is reduced and bound to carbon monoxide. The extinction coefficient of this complex is 91 mM(-1) cm(-1). Electrons from NADPH are transferred to cytochrome P-450K via the NADPH-cytochrome c reductase. The reduction rate of cytochrome P-450K is stimulated by added fatty acids and the reduction kinetics reveal the presence of endogenous substrates bound to cytochrome P-450K. Both cytochrome P-450K concentration and fatty acid hydroxylation activity in kidney microsomes are increased by starvation. On the other hand, phenobarbital treatment of the rats has no effect on either the hemoprotein or the overall hydroxylation reaction and 3,4-benzpyrene administration induces a new species of cytochrome P-450K not involved in fatty acid hydroxylation. Cytochrome P-450K shows, in contrast to liver P-450, high substrate specificity. The only substances forming enzyme-substrate complexes with cytochrome P-450K are the medium-chained fatty acids and certain derivatives of these acids. The chemical requirements for substrate binding include a carbon chain of medium length and at the end of the chain a carbonyl group and a free electron pair on a neighbouring atom. The distance between the binding site for the carbonyl group and the active oxygen is suggested to be in the order of 16 A. This distance fixes the ratio of omega- and (omega-1)-hydroxylated products formed from a certain fatty acid by the single species of cytochrome P-450K involved. The membrane microenvironment seems also to be of importance for the substrate specificity of cytochrome P-450K, since removal of the cytochrome from the membrane lowers its binding specificity to some extent. A comparison between the liver and kidney cytochrome P-450 systems suggests that the kidney cytochrome P-450K system is specialized for fatty acid hydroxylation.", "contents": "Fatty acid hydroxylation in rat kidney cortex microsomes. Rat kidney microsomes have been found to catalyze the hydroxylation of medium-chained fatty acids to the omega- and (omego-1)-hydroxy derivatives. This reaction, which requires NADPH and molecular oxygen, is a function of monooxygenase system present in the kidney microsomes, containing NADPH-cytochrome c reductase and cytochrome P-450K. NADH is about half as effective as an electron donor as NADPH and there is an additive effect in the presence of both nucleotides. Cytochrome P-450K absorbs light maximally at 452-3 nm, when it is reduced and bound to carbon monoxide. The extinction coefficient of this complex is 91 mM(-1) cm(-1). Electrons from NADPH are transferred to cytochrome P-450K via the NADPH-cytochrome c reductase. The reduction rate of cytochrome P-450K is stimulated by added fatty acids and the reduction kinetics reveal the presence of endogenous substrates bound to cytochrome P-450K. Both cytochrome P-450K concentration and fatty acid hydroxylation activity in kidney microsomes are increased by starvation. On the other hand, phenobarbital treatment of the rats has no effect on either the hemoprotein or the overall hydroxylation reaction and 3,4-benzpyrene administration induces a new species of cytochrome P-450K not involved in fatty acid hydroxylation. Cytochrome P-450K shows, in contrast to liver P-450, high substrate specificity. The only substances forming enzyme-substrate complexes with cytochrome P-450K are the medium-chained fatty acids and certain derivatives of these acids. The chemical requirements for substrate binding include a carbon chain of medium length and at the end of the chain a carbonyl group and a free electron pair on a neighbouring atom. The distance between the binding site for the carbonyl group and the active oxygen is suggested to be in the order of 16 A. This distance fixes the ratio of omega- and (omega-1)-hydroxylated products formed from a certain fatty acid by the single species of cytochrome P-450K involved. The membrane microenvironment seems also to be of importance for the substrate specificity of cytochrome P-450K, since removal of the cytochrome from the membrane lowers its binding specificity to some extent. A comparison between the liver and kidney cytochrome P-450 systems suggests that the kidney cytochrome P-450K system is specialized for fatty acid hydroxylation."}
{"id": "PMID:241012", "title": "Studies of 3-aminopyridine adenine dinucleotide phosphate.", "content": "3-Aminopyridine adenine dinucleotide phosphate (AADP) was prepared from NADP and 3-amino-pyridine through the pig brain NADase-catalyzed pyridine base exchange reaction. The purified dinucleotide was chemically characterized and spectral properties of the compound were determined. The importance of the application of AADP in studies of NADP-requiring biochemical processes was indicated by the demonstration of AADP as an effective inhibitor of five NADP-requiring enzymes, by the demonstration of the fluorescence enhancement on the binding of AADP to yeast glucose-6-phosphate dehydrogenase when glucose-6-phosphate is present, and by the functioning of AADP as a fluorimetric substrate for snake venom nucleotide pyrophosphatase.", "contents": "Studies of 3-aminopyridine adenine dinucleotide phosphate. 3-Aminopyridine adenine dinucleotide phosphate (AADP) was prepared from NADP and 3-amino-pyridine through the pig brain NADase-catalyzed pyridine base exchange reaction. The purified dinucleotide was chemically characterized and spectral properties of the compound were determined. The importance of the application of AADP in studies of NADP-requiring biochemical processes was indicated by the demonstration of AADP as an effective inhibitor of five NADP-requiring enzymes, by the demonstration of the fluorescence enhancement on the binding of AADP to yeast glucose-6-phosphate dehydrogenase when glucose-6-phosphate is present, and by the functioning of AADP as a fluorimetric substrate for snake venom nucleotide pyrophosphatase."}
{"id": "PMID:241013", "title": "[Tuberous sclerosis as cause of neuropathological symptoms allegedly due to smallpox vaccination (author's transl)].", "content": "Following smallpox vaccination a patient presented with neuropathological symptoms, the real cause of which was tuberous sclerosis, a congenital disease.", "contents": "[Tuberous sclerosis as cause of neuropathological symptoms allegedly due to smallpox vaccination (author's transl)]. Following smallpox vaccination a patient presented with neuropathological symptoms, the real cause of which was tuberous sclerosis, a congenital disease."}
{"id": "PMID:241014", "title": "[The medicinal treatment of anxiety in alcoholism in the withdrawal stage (author's transl)].", "content": "The benzodiazepine preparation Camazepam was tested for its anxiolytic activity and found to be effective. It differs from preparations which have already been in use for a long time, especially by the lack of any hypnotic and muscle relaxant effects. In the clinical trial it was also free from side effects so far as they could be detected by the usual routine investigations of the technical laboratory.", "contents": "[The medicinal treatment of anxiety in alcoholism in the withdrawal stage (author's transl)]. The benzodiazepine preparation Camazepam was tested for its anxiolytic activity and found to be effective. It differs from preparations which have already been in use for a long time, especially by the lack of any hypnotic and muscle relaxant effects. In the clinical trial it was also free from side effects so far as they could be detected by the usual routine investigations of the technical laboratory."}
{"id": "PMID:241018", "title": "Cerebrospinal-fluid acid base and electrolyte changes resulting from cerebral anoxia in man.", "content": "To study metabolic changes in the central nervous system after profound anoxia, we measured changes in cisternal and lumbar cerebrospinal fluid. Acid-base values and electrolyte concentrations were determined in cisternal and lumbar fluid from 12 severely anoxic patients (cardiac arrest), and from 15 within 24 hours after cardiac resuscitation. In the severely anoxia patients the normal cisternal-lumbar pH gradient was reversed, cisternal fluid was more acid (pH 6.815 vs. 6.953), and cisternal potassium concentration was twice that of lumbar (6.7 vs 3.5 mEq per liter). These findings indicate that during anoxia potassium and hydrogen ion flow from brain cells into the brain extracellular fluid, and that acute changes are reflected more accurately by cisternal than by lumbar fluid. In resuscitated patients cisternal fluid was normal, and normal cisternal-lumbar differences were found; thus, the normal milieu of brain cells is rapidly reestablished after resuscitation.", "contents": "Cerebrospinal-fluid acid base and electrolyte changes resulting from cerebral anoxia in man. To study metabolic changes in the central nervous system after profound anoxia, we measured changes in cisternal and lumbar cerebrospinal fluid. Acid-base values and electrolyte concentrations were determined in cisternal and lumbar fluid from 12 severely anoxic patients (cardiac arrest), and from 15 within 24 hours after cardiac resuscitation. In the severely anoxia patients the normal cisternal-lumbar pH gradient was reversed, cisternal fluid was more acid (pH 6.815 vs. 6.953), and cisternal potassium concentration was twice that of lumbar (6.7 vs 3.5 mEq per liter). These findings indicate that during anoxia potassium and hydrogen ion flow from brain cells into the brain extracellular fluid, and that acute changes are reflected more accurately by cisternal than by lumbar fluid. In resuscitated patients cisternal fluid was normal, and normal cisternal-lumbar differences were found; thus, the normal milieu of brain cells is rapidly reestablished after resuscitation."}
{"id": "PMID:241024", "title": "Effect of hypophysectomy on cAMP changes in rat adrenal medulla evoked by catecholamines and carbamylcholine.", "content": "It was the aim of this study to investigate the mechanisms responsible for changes in 3',5'-cyclic adenosine monophosphate (cAMP) in the rat adrenal medulla occuring after administration of carbamylcholine, histamine, ACTH and various phenylethylamines. Carbamylcholine, ACTH, histamine, noradrenaline and dopamine produced marked (500-900%) increases in adrenal cAMP which were very similar in both adrenal cortex and medulla both with respect to time-course and relative extent. Interestingly isoprenaline and adrenaline did not influence cAMP levels even at excessively high doses. In all cases studied transsection of the splanchnic fibers supplying the adrenals reduced the increase in medullary cAMP by not more than 25--30%, suggesting that cAMP levels in the adrenal medulla are predominantly regulated by non-neuronal mechanisms. This assumption was strongly supported by the observation that hypophysectomy completely abolished the 500--600% increase in cAMP produced by 50 mumol/kg of dopamine and reduced the 700% increase resulting from 4.4 mumol/kg of carbamylcholine to 70%. In spite of the marked increase in cAMP produced by single and repeated doses of dopamine in the adrenal medulla there was no subsequent induction of tyrosine hydroxylase (TH). Moreover carbamylcholine (8.2 mumol/kg) evoked TH induction only in innervated adrenals whereas after denervation, in spite of the large (+ 500%) and prolonged (more than 90 min) increase in cAMP, no TH induction could be observed. It is concluded that adrenal medullary cAMP is predominantly regulated by the pituitary gland via the adrenal cortex and only to a much smaller extent--if at all--by direct cholinergic mechanisms, which are responsible for the initiation of TH induction.", "contents": "Effect of hypophysectomy on cAMP changes in rat adrenal medulla evoked by catecholamines and carbamylcholine. It was the aim of this study to investigate the mechanisms responsible for changes in 3',5'-cyclic adenosine monophosphate (cAMP) in the rat adrenal medulla occuring after administration of carbamylcholine, histamine, ACTH and various phenylethylamines. Carbamylcholine, ACTH, histamine, noradrenaline and dopamine produced marked (500-900%) increases in adrenal cAMP which were very similar in both adrenal cortex and medulla both with respect to time-course and relative extent. Interestingly isoprenaline and adrenaline did not influence cAMP levels even at excessively high doses. In all cases studied transsection of the splanchnic fibers supplying the adrenals reduced the increase in medullary cAMP by not more than 25--30%, suggesting that cAMP levels in the adrenal medulla are predominantly regulated by non-neuronal mechanisms. This assumption was strongly supported by the observation that hypophysectomy completely abolished the 500--600% increase in cAMP produced by 50 mumol/kg of dopamine and reduced the 700% increase resulting from 4.4 mumol/kg of carbamylcholine to 70%. In spite of the marked increase in cAMP produced by single and repeated doses of dopamine in the adrenal medulla there was no subsequent induction of tyrosine hydroxylase (TH). Moreover carbamylcholine (8.2 mumol/kg) evoked TH induction only in innervated adrenals whereas after denervation, in spite of the large (+ 500%) and prolonged (more than 90 min) increase in cAMP, no TH induction could be observed. It is concluded that adrenal medullary cAMP is predominantly regulated by the pituitary gland via the adrenal cortex and only to a much smaller extent--if at all--by direct cholinergic mechanisms, which are responsible for the initiation of TH induction."}
{"id": "PMID:241025", "title": "Effect of bulbocapnine as a peripheral dopamine receptor antagonists in the anesthetized cat.", "content": "We have found bulbocapnine to be an effective, apparently competitive inhibitor of dopamine depressor responses in the anesthetized, phenoxybenzamine-treated cat. The duration of action of the compound as a dopaminergic antagonist exceeded 3 hrs after an intravenous dose of 8 mg/kg. In the same preparation, however bulbocapnine did not at all inhibit the depressor responses to acetylcholine, histamine and isoproterenol, indicating a selectivity of action. Although administration of a high dose of propranolol (2 mg/kg, i.v.) did not alter the response of the alpha-receptor blocked cat to dopamine, the subsequent infusion of bulbocapnine remained effective. These results suggest that dopamine is acting as a blood pressure depressor agent via a unique receptor mechanism.", "contents": "Effect of bulbocapnine as a peripheral dopamine receptor antagonists in the anesthetized cat. We have found bulbocapnine to be an effective, apparently competitive inhibitor of dopamine depressor responses in the anesthetized, phenoxybenzamine-treated cat. The duration of action of the compound as a dopaminergic antagonist exceeded 3 hrs after an intravenous dose of 8 mg/kg. In the same preparation, however bulbocapnine did not at all inhibit the depressor responses to acetylcholine, histamine and isoproterenol, indicating a selectivity of action. Although administration of a high dose of propranolol (2 mg/kg, i.v.) did not alter the response of the alpha-receptor blocked cat to dopamine, the subsequent infusion of bulbocapnine remained effective. These results suggest that dopamine is acting as a blood pressure depressor agent via a unique receptor mechanism."}
{"id": "PMID:241029", "title": "The effect of pre- and postnatal undernutrition on the development of the cerebellar cortex in the rat. II. Histochemical observations.", "content": "The effect of pre- and postnatal undernutrition on the neuronal enzymatic maturation of the neocerebellar hemispheral lobules VI b, VI c and VII (according to Larsell 1952) was studied. Postnatally oxidative enzyme histochemistry (LDH, SDH, NADH, NADPH, G6PDH) revealed a delayed enzymatic development in the cerebellum between days 8 and 22, as an effect of pre- and postnatal undernutrition. In the Purkinje cell apical cone a delayed increase in enzyme activities could be seen at days 8 to 11 as well as a delayed decrease in Purkinje cell perikaryal enzyme activities at days 11 to 14 post-partum. The retarded enzymatic development seemed to parallel the retarded morphological development (cf. Sima & Persson 1975).", "contents": "The effect of pre- and postnatal undernutrition on the development of the cerebellar cortex in the rat. II. Histochemical observations. The effect of pre- and postnatal undernutrition on the neuronal enzymatic maturation of the neocerebellar hemispheral lobules VI b, VI c and VII (according to Larsell 1952) was studied. Postnatally oxidative enzyme histochemistry (LDH, SDH, NADH, NADPH, G6PDH) revealed a delayed enzymatic development in the cerebellum between days 8 and 22, as an effect of pre- and postnatal undernutrition. In the Purkinje cell apical cone a delayed increase in enzyme activities could be seen at days 8 to 11 as well as a delayed decrease in Purkinje cell perikaryal enzyme activities at days 11 to 14 post-partum. The retarded enzymatic development seemed to parallel the retarded morphological development (cf. Sima & Persson 1975)."}
{"id": "PMID:241031", "title": "Effects of stress on catecholamines and tyrosine hydroxylase activity of individual hypothalamic nuclei.", "content": "The effects of acute stress on norepinephrine (NE) and dopamine (DA) concentrations and of repeated stress on tyrosine hydroxylase (TH) activity were measured in individual hypothalamic nuclei and other rat brain regions. A microdissection technique and radioisotopic enzymatic assays enables these studies to be performed. NE and DA concentrations were reduced and TH activity increased selectively in the arcuate nucleus. These results suggest that the arcuate nucleus may be selectively involved in the stress response and support the hypothesis that catecholamines in the medial basal hypothalamus mediate certain of the neuroendocrine changes observed in stress.", "contents": "Effects of stress on catecholamines and tyrosine hydroxylase activity of individual hypothalamic nuclei. The effects of acute stress on norepinephrine (NE) and dopamine (DA) concentrations and of repeated stress on tyrosine hydroxylase (TH) activity were measured in individual hypothalamic nuclei and other rat brain regions. A microdissection technique and radioisotopic enzymatic assays enables these studies to be performed. NE and DA concentrations were reduced and TH activity increased selectively in the arcuate nucleus. These results suggest that the arcuate nucleus may be selectively involved in the stress response and support the hypothesis that catecholamines in the medial basal hypothalamus mediate certain of the neuroendocrine changes observed in stress."}
{"id": "PMID:241034", "title": "[Gamma glutamly transpeptidase in chronic anicteric hepatopathies].", "content": "Serum levels of gammaGT were determined in 51 patients suffering from bioptically verified chronic anictereric liber disease. GammaGT proved to be much more sensitive than the other enzymes studied and presented a significant increase particularly in cases of steatosis and chronic \"alcoholic\" liver disease with a markedly steatosic character.", "contents": "[Gamma glutamly transpeptidase in chronic anicteric hepatopathies]. Serum levels of gammaGT were determined in 51 patients suffering from bioptically verified chronic anictereric liber disease. GammaGT proved to be much more sensitive than the other enzymes studied and presented a significant increase particularly in cases of steatosis and chronic \"alcoholic\" liver disease with a markedly steatosic character."}
{"id": "PMID:241035", "title": "Utilization of dietary calcium by iron-deficient rats.", "content": "Iron deficiency causes cytological and enzymic changes in the gastrointestinal mucosa of animals and man that can be expected to impair the digestion and absorption of other nutrients. In experiment 1, healthy, weanling, female rats were grouped into pair-mates and pair-fed either an iron-deficient or an iron-supplemented diet for 19 weeks. In experiment 2, iron-deficient offspring reared by iron-deficient females were grouped into pair-mates and pair-fed either an iron-deficient or an iron-supplemented diet for 15 weeks. In experiment 1, apparent absorption of calcium was significantly depressed in week 9 (p less than 0.001) and slightly depressed in weeks 10 and 11. In experiment 2, the apparent absorption of calcium was significantly (p less than 0.001) depressed in weeks 6, 13, and 14. Absorption was not measured in other weeks in these experiments. The concentrations of calcium and magnesium were consistently higher in the fecal dry matter of the iron deficient rats in both experiments. It was concluded that any defects in digestion and absorption by the iron-deficient rats was confined primarily to the mineral nutrients because in both experiments apparent absorption of dry matter was consistently higher in these animals compared to their iron-supplemented pair-mates.", "contents": "Utilization of dietary calcium by iron-deficient rats. Iron deficiency causes cytological and enzymic changes in the gastrointestinal mucosa of animals and man that can be expected to impair the digestion and absorption of other nutrients. In experiment 1, healthy, weanling, female rats were grouped into pair-mates and pair-fed either an iron-deficient or an iron-supplemented diet for 19 weeks. In experiment 2, iron-deficient offspring reared by iron-deficient females were grouped into pair-mates and pair-fed either an iron-deficient or an iron-supplemented diet for 15 weeks. In experiment 1, apparent absorption of calcium was significantly depressed in week 9 (p less than 0.001) and slightly depressed in weeks 10 and 11. In experiment 2, the apparent absorption of calcium was significantly (p less than 0.001) depressed in weeks 6, 13, and 14. Absorption was not measured in other weeks in these experiments. The concentrations of calcium and magnesium were consistently higher in the fecal dry matter of the iron deficient rats in both experiments. It was concluded that any defects in digestion and absorption by the iron-deficient rats was confined primarily to the mineral nutrients because in both experiments apparent absorption of dry matter was consistently higher in these animals compared to their iron-supplemented pair-mates."}
{"id": "PMID:241036", "title": "Correlation of fetal heart rate-uterine contraction patterns with fetal scalp blood pH.", "content": "The significance of fetal heart rate-uterine contraction (FHR-UC) monitoring as a means of predicting the condition of the fetus during labor was studied by correlating 460 fetal pH determinations obtained from 216 patients with the analysis of the 20-minute FHR-UC record preceding the fetal scalp blood sample. Both qualitative and quantitative analyses of the FHR-UC record were performed. The results indicate a less than 10% chance of fetal pH less than or equal to 7.250 with an normal baseline FHR and no periodic changes or with periodic accelerations, early decelerations, and uncomplicated baseline bradycardia or tachycardia. Variable or delayed decelerations with a total surface area (TSA) of 1-100 for the 20-min period were associated with a fetal pH less than or equal to 7.250 in 23 and 34% of cases, respectively. Variable or delayed decelerations with a TSA greater than 100 had a 35 or 47% chance of fetal pH less than or equall to 7.250. It is concluded that FHR-UC monitoring can be used to screen the innocuous from the ominous periodic change but that fetal scalp blood pH must be obtained to identify accurately the true from the false-positive ominous pattern.", "contents": "Correlation of fetal heart rate-uterine contraction patterns with fetal scalp blood pH. The significance of fetal heart rate-uterine contraction (FHR-UC) monitoring as a means of predicting the condition of the fetus during labor was studied by correlating 460 fetal pH determinations obtained from 216 patients with the analysis of the 20-minute FHR-UC record preceding the fetal scalp blood sample. Both qualitative and quantitative analyses of the FHR-UC record were performed. The results indicate a less than 10% chance of fetal pH less than or equal to 7.250 with an normal baseline FHR and no periodic changes or with periodic accelerations, early decelerations, and uncomplicated baseline bradycardia or tachycardia. Variable or delayed decelerations with a total surface area (TSA) of 1-100 for the 20-min period were associated with a fetal pH less than or equal to 7.250 in 23 and 34% of cases, respectively. Variable or delayed decelerations with a TSA greater than 100 had a 35 or 47% chance of fetal pH less than or equall to 7.250. It is concluded that FHR-UC monitoring can be used to screen the innocuous from the ominous periodic change but that fetal scalp blood pH must be obtained to identify accurately the true from the false-positive ominous pattern."}
{"id": "PMID:241038", "title": "Puncture wounds of the foot.", "content": "Serious complications occurred in 29 of 887 children with puncture wounds of the feet treated over a four-year period at the Dr. Charles A. Janeway Child Health Centre. Osteomyelitis in one of the small bones of the foot was the commonest complication and occurred when a cartilaginous surface (physeal plate or articular cartilage) had been violated. Although systemic signs of osteomyelitis frequently are absent, this infectious process is refractory to medical management. The combined surgical and medical management of this complication is outlined. Management of puncture wounds in the emergency room should include a thorough history concisely recorded, tetanus prophylaxis, and cleansing, debridement, and probing of the wound. Antimicrobial agents are not routinely required but should be reserved for patients presenting late with cellulitis or an established infection. A semisynthetic penicillinase-penicillin appears to be the agent of choice until the results of microbiologic studies are available.", "contents": "Puncture wounds of the foot. Serious complications occurred in 29 of 887 children with puncture wounds of the feet treated over a four-year period at the Dr. Charles A. Janeway Child Health Centre. Osteomyelitis in one of the small bones of the foot was the commonest complication and occurred when a cartilaginous surface (physeal plate or articular cartilage) had been violated. Although systemic signs of osteomyelitis frequently are absent, this infectious process is refractory to medical management. The combined surgical and medical management of this complication is outlined. Management of puncture wounds in the emergency room should include a thorough history concisely recorded, tetanus prophylaxis, and cleansing, debridement, and probing of the wound. Antimicrobial agents are not routinely required but should be reserved for patients presenting late with cellulitis or an established infection. A semisynthetic penicillinase-penicillin appears to be the agent of choice until the results of microbiologic studies are available."}
{"id": "PMID:241040", "title": "Factors affecting surface changes in intact cercariae and cercarial bodies of Schistosoma mansoni.", "content": "The effect of different incubation media and of temperature on the induction of water sensitivity has been investigated in intact and tailless Schistosoma mansoni cercariae. Removal of the cercarial tail by vortex stirring and elevation of the temperature of the medium from 27 to 37 degrees C resulted in the rapid onset of permeability changes in the larvae. The rate of change was greater in water than in TC-199 or Hanks' BSS media. Lowering the pH of the medium or increasing the concentration of Ca2+ ions decreased the rate of permeability change: raising the pH of the medium or the addition of 10(-5) M EDTA enhanced the rate. Raising the temperature of the medium also increased the rate of permeability change in intact cercariae although the rates obtained varied with the different media tested, being greatest in TC-199. It is concluded that both temperature elevation and loss of the cercarial tail influence the onset and rate of permeability changes in cercarial bodies during the transformation to schistosomula.", "contents": "Factors affecting surface changes in intact cercariae and cercarial bodies of Schistosoma mansoni. The effect of different incubation media and of temperature on the induction of water sensitivity has been investigated in intact and tailless Schistosoma mansoni cercariae. Removal of the cercarial tail by vortex stirring and elevation of the temperature of the medium from 27 to 37 degrees C resulted in the rapid onset of permeability changes in the larvae. The rate of change was greater in water than in TC-199 or Hanks' BSS media. Lowering the pH of the medium or increasing the concentration of Ca2+ ions decreased the rate of permeability change: raising the pH of the medium or the addition of 10(-5) M EDTA enhanced the rate. Raising the temperature of the medium also increased the rate of permeability change in intact cercariae although the rates obtained varied with the different media tested, being greatest in TC-199. It is concluded that both temperature elevation and loss of the cercarial tail influence the onset and rate of permeability changes in cercarial bodies during the transformation to schistosomula."}
{"id": "PMID:241041", "title": "[S\u00e9zary's syndrome].", "content": "In S\u00e9zary's syndrome (SS), cutaneous manifestations are associated with an abnormal mononuclear cell in the blood. Clinically, the differential diagnosis with Mycosis fungoides is impossible. However, some of the symptoms are more in favor of SS, such as leonin face, palm and sole hyperkeratosis and changes in pigmentation. The diagnosis of SS rests upon the identification on ordinary blood smears of a lymphocytic cell, the size of which is variable and which exhibits a grooved, folded and lobulated nucleus. This cell is negative for both esterases and peroxydases. It is not a monocyte. Large cells have big nuclei with tetraploid DNA values, whereas small variants have near diploid values. Chromosome analysis may reveal near hypertetraploid, hyper or hypodiploid counts. Marker chromosomes have been seen which could be common to all types. However, many cases are known in which the karyotype was normal. In addition, there are cases in which chromosome analysis was impossible due to poor responses of the S\u00e9zary cells to PHA. As regards surface markers, there is general agreement that S\u00e9zary's cells are non-B lymphocytes. In some cases, the cells had both T markers (antigen and E-rosettes), whereas in others, only one (antigen) was expressed. In still other cases, the abnormal blood cell had neither B nor T markers. In at least one case, the cells had both B and T surface receptors. The diversity of the S\u00e9zary's cell would be explained by the immunologic pressure exerted upon skin lymphocytes by the epidermis due to a change in the antigenicity of this tissue in relation to ageing or to the presence of exogenous chemicals, or to physically induced mutations. Recent studies from this laboratory, using autoradiography after incorporation of tritiated thymidine, have shown labelled lymphocytes in the skin of three out of four cases of SS. These results suggest that cutaneous manifestations in SS, as well as in Mycosis fungoides, are comparable to a chronic Graft-Versus-Host reaction (GVH).", "contents": "[S\u00e9zary's syndrome]. In S\u00e9zary's syndrome (SS), cutaneous manifestations are associated with an abnormal mononuclear cell in the blood. Clinically, the differential diagnosis with Mycosis fungoides is impossible. However, some of the symptoms are more in favor of SS, such as leonin face, palm and sole hyperkeratosis and changes in pigmentation. The diagnosis of SS rests upon the identification on ordinary blood smears of a lymphocytic cell, the size of which is variable and which exhibits a grooved, folded and lobulated nucleus. This cell is negative for both esterases and peroxydases. It is not a monocyte. Large cells have big nuclei with tetraploid DNA values, whereas small variants have near diploid values. Chromosome analysis may reveal near hypertetraploid, hyper or hypodiploid counts. Marker chromosomes have been seen which could be common to all types. However, many cases are known in which the karyotype was normal. In addition, there are cases in which chromosome analysis was impossible due to poor responses of the S\u00e9zary cells to PHA. As regards surface markers, there is general agreement that S\u00e9zary's cells are non-B lymphocytes. In some cases, the cells had both T markers (antigen and E-rosettes), whereas in others, only one (antigen) was expressed. In still other cases, the abnormal blood cell had neither B nor T markers. In at least one case, the cells had both B and T surface receptors. The diversity of the S\u00e9zary's cell would be explained by the immunologic pressure exerted upon skin lymphocytes by the epidermis due to a change in the antigenicity of this tissue in relation to ageing or to the presence of exogenous chemicals, or to physically induced mutations. Recent studies from this laboratory, using autoradiography after incorporation of tritiated thymidine, have shown labelled lymphocytes in the skin of three out of four cases of SS. These results suggest that cutaneous manifestations in SS, as well as in Mycosis fungoides, are comparable to a chronic Graft-Versus-Host reaction (GVH)."}
{"id": "PMID:241042", "title": "Study of renal functions by repeated constant infusion of radiotracers before and after initiation of therapy in hypertension or in diabetes mellitus.", "content": "Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were simultaneously measured by obtaining an isotopic steady state during a continuous infusion of 125I orthoiodohippurate (OIHA). A good correlation was found between the clearances of Ioth (y) and of inulin or polyfructosan (x) : y = 1.18 X (x) + 8.43 (r = 0.96; P less than 0.001) and between the clearances of OIHA (y') and of PAH (x') : y' = 0.62 X (x') + 21.2 (r = 0.93; P less than 0.001). When renal functions were impaired the use of Ioth was not convenient since the infusion time necessary to reach a radioactive plateau was longer than 3 hours. On the contrary, excellent results were obtained by using OIHA. In this case, the main advantages were the absence of urine collection and the rapid obtention of an isotopic equilibrium. The repeated determination of renal clearances in hypertensive or diabetic patients appears to be useful in the study of changes induced by antihypertensive drugs or insulin. Clearances were slightly improved by clonidine, claimed to be useful in hypertension associated with chronic renal failure. GFR and ERPF were rapidly increased by insure on the metabolic and hemodynamic changes induced by insulin than on the return to normal of glomerular basement membrane permeability.", "contents": "Study of renal functions by repeated constant infusion of radiotracers before and after initiation of therapy in hypertension or in diabetes mellitus. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were simultaneously measured by obtaining an isotopic steady state during a continuous infusion of 125I orthoiodohippurate (OIHA). A good correlation was found between the clearances of Ioth (y) and of inulin or polyfructosan (x) : y = 1.18 X (x) + 8.43 (r = 0.96; P less than 0.001) and between the clearances of OIHA (y') and of PAH (x') : y' = 0.62 X (x') + 21.2 (r = 0.93; P less than 0.001). When renal functions were impaired the use of Ioth was not convenient since the infusion time necessary to reach a radioactive plateau was longer than 3 hours. On the contrary, excellent results were obtained by using OIHA. In this case, the main advantages were the absence of urine collection and the rapid obtention of an isotopic equilibrium. The repeated determination of renal clearances in hypertensive or diabetic patients appears to be useful in the study of changes induced by antihypertensive drugs or insulin. Clearances were slightly improved by clonidine, claimed to be useful in hypertension associated with chronic renal failure. GFR and ERPF were rapidly increased by insure on the metabolic and hemodynamic changes induced by insulin than on the return to normal of glomerular basement membrane permeability."}
{"id": "PMID:241043", "title": "[Study of the criteria of evaluation of the exercise capacity of the chronic hemodialyzed subject].", "content": "Direct measurement methods (or the forecast related to indirect measurements) of the maximal oxygen uptake are reviewed. 15 patients suffering from renal failure, performed a total of 28 exercises. One can draw the conclusion that the maximum VO2 is inferior in these subjects to the values usually determined in normal healthy subjects of the same age. This decrease can be significantly correlated with the haematocrit. Comparison between direct measurement methods of the maximal oxygen uptake and indirect methods allowing its forecast from the heart rate, shows that only direct methods are to be used in these patients.", "contents": "[Study of the criteria of evaluation of the exercise capacity of the chronic hemodialyzed subject]. Direct measurement methods (or the forecast related to indirect measurements) of the maximal oxygen uptake are reviewed. 15 patients suffering from renal failure, performed a total of 28 exercises. One can draw the conclusion that the maximum VO2 is inferior in these subjects to the values usually determined in normal healthy subjects of the same age. This decrease can be significantly correlated with the haematocrit. Comparison between direct measurement methods of the maximal oxygen uptake and indirect methods allowing its forecast from the heart rate, shows that only direct methods are to be used in these patients."}
{"id": "PMID:241044", "title": "[Quantitative study of multimolecular forms of serum gamma glutamyl transferase by polyacrylamide gel electrophoresis].", "content": "The quantitative distribution of the multimolecular forms of serum gamma-glutamyl-transferase is studied in 286 sera by acrylamide gel electrophoresis, incubation, coloration in situ, photography, slide reading and integration. In 43 normal sera, the fast fraction represents 66% of the total activity; the ratio of the mean fast fraction to the medium and slow fraction was 2. During pregnancy (53 cases), in cord blood (54 cases), in hepatic cytolysis or cholestasis (55 cases), and in secondary liver carcinoma (21 cases), this ratio is considerably lower, demonstrating the predominance of medium and slow fractions. A similar decrease in the ratio, with predominance of the medium and slow fractions was seen in 22 cases of advanced cancer without metastases in the liver.", "contents": "[Quantitative study of multimolecular forms of serum gamma glutamyl transferase by polyacrylamide gel electrophoresis]. The quantitative distribution of the multimolecular forms of serum gamma-glutamyl-transferase is studied in 286 sera by acrylamide gel electrophoresis, incubation, coloration in situ, photography, slide reading and integration. In 43 normal sera, the fast fraction represents 66% of the total activity; the ratio of the mean fast fraction to the medium and slow fraction was 2. During pregnancy (53 cases), in cord blood (54 cases), in hepatic cytolysis or cholestasis (55 cases), and in secondary liver carcinoma (21 cases), this ratio is considerably lower, demonstrating the predominance of medium and slow fractions. A similar decrease in the ratio, with predominance of the medium and slow fractions was seen in 22 cases of advanced cancer without metastases in the liver."}
{"id": "PMID:241048", "title": "Hemophilus and pneumococcal peritonitis in children with the nephrotic syndrome.", "content": "Two children are reported whose nephrotic syndrome was complicated by peritonitis due to H. influenzae type b. In Pittsburgh, the leading organism for peritonitis in nephrosis remains D. pneumoniae with a disproportionately high incidence in black children. Although H. influenzae is a rare cause of this complication, it should be considered along with the other previously recognized etiological bacterial agents.", "contents": "Hemophilus and pneumococcal peritonitis in children with the nephrotic syndrome. Two children are reported whose nephrotic syndrome was complicated by peritonitis due to H. influenzae type b. In Pittsburgh, the leading organism for peritonitis in nephrosis remains D. pneumoniae with a disproportionately high incidence in black children. Although H. influenzae is a rare cause of this complication, it should be considered along with the other previously recognized etiological bacterial agents."}
{"id": "PMID:241050", "title": "Susceptibility to interference effects in short-term memory of normal and retarded readers.", "content": "The short-term memory for serial order of third and fourth grade normal and retarded readres (Ns = 13) was studied. Six pictures of common objects were spatially presented and subjects were required to reconstruct the sequence. On the first six trials, the same pictures were repeatedly presented in different sequences. On the seventh trial, a new set of stimuli was introduced. Analysis of short-term memory over trials showed that normal and retarded readers were similar on Trial 1 but the performance of retarded readers deteriorated more over trials than the performance of normal readers. Short-term memory of both groups improved on Trial 7. The results indicate a greater susceptibility to interference in the short-term memory of retarded readers.", "contents": "Susceptibility to interference effects in short-term memory of normal and retarded readers. The short-term memory for serial order of third and fourth grade normal and retarded readres (Ns = 13) was studied. Six pictures of common objects were spatially presented and subjects were required to reconstruct the sequence. On the first six trials, the same pictures were repeatedly presented in different sequences. On the seventh trial, a new set of stimuli was introduced. Analysis of short-term memory over trials showed that normal and retarded readers were similar on Trial 1 but the performance of retarded readers deteriorated more over trials than the performance of normal readers. Short-term memory of both groups improved on Trial 7. The results indicate a greater susceptibility to interference in the short-term memory of retarded readers."}
{"id": "PMID:241051", "title": "Effects of pH and ionic strength on the potassium system in the internally perfused giant barnacle muscle fibre.", "content": "Membrane potentials in single barnacle muscle fibres of Megabalanus psittacus, internally perfused with 200 mM K-acetate (KAc) solution of pH 7.5 were in the range --53 to --60 mV. These were followed as a function of pH of the external chloride saline. Decrease of pH of the Cl-saline from 8.5 to 3.5 hyperpolarized the membrane reversibly by about 8 mV. On further decrease of pH to 3.0, a transient hyperpolarization (from --60 to --65 mV) followed by a sudden and irreversible drop of potential to --40 mV was observed. Replacement of the external Cl-saline by acetate saline in the pH range 8.5 to 6.5 had no effect on the membrane potential. Further decrease of pH to 5.0 brought about an irreversible reduction of membrane potential. For fibres bathing in Cl- or Ac-saline at pH 7.5 when the internal pH was changed to 5.5, a transient hyperpolarization in Cl-saline and a sustained hyperpolarization in Ac-saline were observed. Further studies of membrane potential changing the concentration of external K, keeping the concentration of Cl or Ac constant, and changing the concentration of Cl or Ac, keeping the concentration of K constant, at different internal and external pHs showed that as the pH was reduced the membrane became more permeable to anions, Cl being more permeable than Ac. Experiments in which the membrane potential was controlled showed that when the internal pH of 200 mM KAc solution was reduced from 7.5 to 6.5 or raised to 8.5, the changes in outward K currents at various depolarizations were negligible. However, when the pH was reduced to 5.5 or 5.0, there was a progressive decrease in the outward K currents. The leakage currents in all these cases were relatively small. Use of high ionic strength solution of 580 mM KAc internally protected the K system in that when the pH was lowered the depression of the outward K current was smaller than that observed at a corresponding pH when the internal solution was 200 mM KAc. Use of low ionic strength solution of 50 mM KAc had the opposite effect. The results have been explained in terms of the ion exchange theory by postulating that the membrane has fixed amphoteric groups.", "contents": "Effects of pH and ionic strength on the potassium system in the internally perfused giant barnacle muscle fibre. Membrane potentials in single barnacle muscle fibres of Megabalanus psittacus, internally perfused with 200 mM K-acetate (KAc) solution of pH 7.5 were in the range --53 to --60 mV. These were followed as a function of pH of the external chloride saline. Decrease of pH of the Cl-saline from 8.5 to 3.5 hyperpolarized the membrane reversibly by about 8 mV. On further decrease of pH to 3.0, a transient hyperpolarization (from --60 to --65 mV) followed by a sudden and irreversible drop of potential to --40 mV was observed. Replacement of the external Cl-saline by acetate saline in the pH range 8.5 to 6.5 had no effect on the membrane potential. Further decrease of pH to 5.0 brought about an irreversible reduction of membrane potential. For fibres bathing in Cl- or Ac-saline at pH 7.5 when the internal pH was changed to 5.5, a transient hyperpolarization in Cl-saline and a sustained hyperpolarization in Ac-saline were observed. Further studies of membrane potential changing the concentration of external K, keeping the concentration of Cl or Ac constant, and changing the concentration of Cl or Ac, keeping the concentration of K constant, at different internal and external pHs showed that as the pH was reduced the membrane became more permeable to anions, Cl being more permeable than Ac. Experiments in which the membrane potential was controlled showed that when the internal pH of 200 mM KAc solution was reduced from 7.5 to 6.5 or raised to 8.5, the changes in outward K currents at various depolarizations were negligible. However, when the pH was reduced to 5.5 or 5.0, there was a progressive decrease in the outward K currents. The leakage currents in all these cases were relatively small. Use of high ionic strength solution of 580 mM KAc internally protected the K system in that when the pH was lowered the depression of the outward K current was smaller than that observed at a corresponding pH when the internal solution was 200 mM KAc. Use of low ionic strength solution of 50 mM KAc had the opposite effect. The results have been explained in terms of the ion exchange theory by postulating that the membrane has fixed amphoteric groups."}
{"id": "PMID:241052", "title": "Calculation of O2 saturation and of the oxyhemoglobin dissociation curve for different species, using a new programmable pocket calculator.", "content": "The degree of O2 saturation and different data of acid-base status are determined from pO2, pH, and pCO2 values bya programmable pocket calculator. Since the operating program should be usable for different species and also in the range of very low O2 saturations, obviously the usual Hill equation for calculating the oxygen dissociation curve of hemoglobin is not applicable; the same is true is some cases for the Adair equation. Thus a 3-fold subdivision of the dissociation curve was undertaken and programmed. Suitable programs for several species could be established despite the limited number of program steps in the new calculator, giving systematic deviations in calculated O2 saturations of less than or equal to +/- 0.9 saturation precent over the full range of dissociation curves. A reverse procedure for calculation of pO2 from saturation is added. In situations where pCO2 or base excess are not known or only estimated, limits of the arising error are stated. In the acid-base program 7 parameters are evaluated partially using empirical formulae derived from nomograms. The programmable pocket calculator offers advantages of small size, economy, and independence of line voltage compared to much more spacious units and a precision equal or superior to nomograms.", "contents": "Calculation of O2 saturation and of the oxyhemoglobin dissociation curve for different species, using a new programmable pocket calculator. The degree of O2 saturation and different data of acid-base status are determined from pO2, pH, and pCO2 values bya programmable pocket calculator. Since the operating program should be usable for different species and also in the range of very low O2 saturations, obviously the usual Hill equation for calculating the oxygen dissociation curve of hemoglobin is not applicable; the same is true is some cases for the Adair equation. Thus a 3-fold subdivision of the dissociation curve was undertaken and programmed. Suitable programs for several species could be established despite the limited number of program steps in the new calculator, giving systematic deviations in calculated O2 saturations of less than or equal to +/- 0.9 saturation precent over the full range of dissociation curves. A reverse procedure for calculation of pO2 from saturation is added. In situations where pCO2 or base excess are not known or only estimated, limits of the arising error are stated. In the acid-base program 7 parameters are evaluated partially using empirical formulae derived from nomograms. The programmable pocket calculator offers advantages of small size, economy, and independence of line voltage compared to much more spacious units and a precision equal or superior to nomograms."}
{"id": "PMID:241053", "title": "The rates of saxitoxin action and of saxitoxin-tetrodotoxin interaction at the node of Ranvier.", "content": "Voltage clamp experiments were done on single nodes of Ranvier of Rana esculenta. Equilibrium effects were obtained from INa-V curves, the rates of action from changes in INa on changing solutions during repetitive depolarizing pulses. 2. Saxitoxin (STX) exclusively and reversibly blocked Na channels, the effect being fully described by a one-to-one reaction between STX and a receptor at the channel with an equilibrium dissociation constant, Ks, of 1.4 nM; the mean offset rate constant k2s, was 1.76 X 10(-2) sec-1 (16 +/- 1 degree C;pH 7.2), 1.7 times the value for tetrodotoxin (TTX). 3. At pH 5.6, K2S WAs increased by a factor of 1.33 while the equilibrium STX effects was decreased in a way suggesting competition between STX and protons. 4. After pretreatment of nodes with 3.1 nM TTX the extra block on adding 9.0 nM STX as well as its relief on taking out STX of the TTX-STX mixture revealed transients in the time course of receptor occupation. 5. These non-monotonic time courses are incompatible with the idea of two independent blocking sites (for STX and TTX) per channel but could be quantitatively fitted by analog-computed curves assuming competition between STX and TTX for the same site.", "contents": "The rates of saxitoxin action and of saxitoxin-tetrodotoxin interaction at the node of Ranvier. Voltage clamp experiments were done on single nodes of Ranvier of Rana esculenta. Equilibrium effects were obtained from INa-V curves, the rates of action from changes in INa on changing solutions during repetitive depolarizing pulses. 2. Saxitoxin (STX) exclusively and reversibly blocked Na channels, the effect being fully described by a one-to-one reaction between STX and a receptor at the channel with an equilibrium dissociation constant, Ks, of 1.4 nM; the mean offset rate constant k2s, was 1.76 X 10(-2) sec-1 (16 +/- 1 degree C;pH 7.2), 1.7 times the value for tetrodotoxin (TTX). 3. At pH 5.6, K2S WAs increased by a factor of 1.33 while the equilibrium STX effects was decreased in a way suggesting competition between STX and protons. 4. After pretreatment of nodes with 3.1 nM TTX the extra block on adding 9.0 nM STX as well as its relief on taking out STX of the TTX-STX mixture revealed transients in the time course of receptor occupation. 5. These non-monotonic time courses are incompatible with the idea of two independent blocking sites (for STX and TTX) per channel but could be quantitatively fitted by analog-computed curves assuming competition between STX and TTX for the same site."}
{"id": "PMID:241055", "title": "[Biological diagnosis of Zollinger-Ellison syndrome in the context of a polyendocrine adenomatosis].", "content": "The diagnostic features of Zollinger-Ellison syndrome (ZES) in patients with type I poly-endocrine adenomatosis with a gastrinoma are analysed on the basis of 11 cases. Both from a clinical (frequency of ulcer disease and of diarrhoea) and biological standpoint (hypersecretion of gastric acid, hypergastrinaemia, or results of secretin stimulation test), the characteristics of ZES are not different whether a gastrinoma is present alone or in association with involvement of other endocrine glands. However the signs may be either masked by changes related to another endocrine disorder or appear late. They should therefore be sought routinely in all patients with an endocrine disorder which might fall into the context of a type I poly-endocrine adenomatosis. The sole difficulty is the interpretation of gastric acid hypersecretion and/or hypergastrinaemia in a patient with hyperparathyroidism. In this latter case, such abnormalities are not necessarily due to ZES and may disappear after removal of the parathyroid adenoma.", "contents": "[Biological diagnosis of Zollinger-Ellison syndrome in the context of a polyendocrine adenomatosis]. The diagnostic features of Zollinger-Ellison syndrome (ZES) in patients with type I poly-endocrine adenomatosis with a gastrinoma are analysed on the basis of 11 cases. Both from a clinical (frequency of ulcer disease and of diarrhoea) and biological standpoint (hypersecretion of gastric acid, hypergastrinaemia, or results of secretin stimulation test), the characteristics of ZES are not different whether a gastrinoma is present alone or in association with involvement of other endocrine glands. However the signs may be either masked by changes related to another endocrine disorder or appear late. They should therefore be sought routinely in all patients with an endocrine disorder which might fall into the context of a type I poly-endocrine adenomatosis. The sole difficulty is the interpretation of gastric acid hypersecretion and/or hypergastrinaemia in a patient with hyperparathyroidism. In this latter case, such abnormalities are not necessarily due to ZES and may disappear after removal of the parathyroid adenoma."}
{"id": "PMID:241061", "title": "The photochemistry of purine components of nucleic acids. I. The efficiency of photolysis of adenine and guanine derivatives in aqueous solution.", "content": "It has been shown that the quantum yield of the photochemical conversion of adenine and the corresponding nucleosides and nucleoside 5'-phosphates in liquid (pH 5.6 and 2.0) and frozen aqueous solutions do not exceed 10(-4). The quantum yield of the photoconversion of guanine-containing nucleosides and nucleoside 5'-phosphates in liquid aqueous solution (pH 5.6) after removal of oxygen by passing through nitrogen and in the frozen state do not exceed 0.3 x 10(-4). The quantum yield in oxygen-containing liquid aqueous solutions increase to 0.3 x 10(-3), i.e. to values commensurate with the quantum yield of pyrimidine photolysis.", "contents": "The photochemistry of purine components of nucleic acids. I. The efficiency of photolysis of adenine and guanine derivatives in aqueous solution. It has been shown that the quantum yield of the photochemical conversion of adenine and the corresponding nucleosides and nucleoside 5'-phosphates in liquid (pH 5.6 and 2.0) and frozen aqueous solutions do not exceed 10(-4). The quantum yield of the photoconversion of guanine-containing nucleosides and nucleoside 5'-phosphates in liquid aqueous solution (pH 5.6) after removal of oxygen by passing through nitrogen and in the frozen state do not exceed 0.3 x 10(-4). The quantum yield in oxygen-containing liquid aqueous solutions increase to 0.3 x 10(-3), i.e. to values commensurate with the quantum yield of pyrimidine photolysis."}
{"id": "PMID:241062", "title": "Complex formation between nuclear RNA and mitochondrial proteins.", "content": "Specific proteins are present in mitochondria that are capable of forming complexes with nuclear RNA. Complex formation is time and temperature dependent and requires optimal conditions of Mg2+, K+ and H+ concentrations. The complexes are stable towards most denaturing agents and their component nucleic acids and proteins are resistant to nucleolysis and proteolysis respectively.", "contents": "Complex formation between nuclear RNA and mitochondrial proteins. Specific proteins are present in mitochondria that are capable of forming complexes with nuclear RNA. Complex formation is time and temperature dependent and requires optimal conditions of Mg2+, K+ and H+ concentrations. The complexes are stable towards most denaturing agents and their component nucleic acids and proteins are resistant to nucleolysis and proteolysis respectively."}
{"id": "PMID:241060", "title": "[Adsorption properties of Beidellite (author's transl)].", "content": "The beidellite is both an activator and an adsorbing agent for certain clotting factors: at low concentration (1 p. 1 000), factors XII and VII of human plasma are activated. At a concentration of 10 p. 1 000, the fibrinogen is totally adsorbed, leaving in the supernatant most of the VIII. At alpha 20 p. 1 000 concentrations, most of factor II remains unabsorbed, the remaining plasma being devoided of other clotting factors except minute amounts of factors XI and XII. Contrarely to bentonite, which has similar properties, beidellite does not absorb water and does not modify the pH. Beidellite is therefore a very useful agent for selective adsorption of clotting factors.", "contents": "[Adsorption properties of Beidellite (author's transl)]. The beidellite is both an activator and an adsorbing agent for certain clotting factors: at low concentration (1 p. 1 000), factors XII and VII of human plasma are activated. At a concentration of 10 p. 1 000, the fibrinogen is totally adsorbed, leaving in the supernatant most of the VIII. At alpha 20 p. 1 000 concentrations, most of factor II remains unabsorbed, the remaining plasma being devoided of other clotting factors except minute amounts of factors XI and XII. Contrarely to bentonite, which has similar properties, beidellite does not absorb water and does not modify the pH. Beidellite is therefore a very useful agent for selective adsorption of clotting factors."}
{"id": "PMID:241069", "title": "Blood parameters in Leucocytozoon smithi infected poults fed clopidol.", "content": "Poults naturally infected with L. smithi demonstrated a significant (P less than 0.01) decrease in arterial PO2 (mm. Hg) during the second and third weeks after exposure to black fly bites. Poults fed Clopidol (0.0125%) during the exposure period and subsequent experimental periods showed very little parasitemia and no significant reduction in arterial PO2.", "contents": "Blood parameters in Leucocytozoon smithi infected poults fed clopidol. Poults naturally infected with L. smithi demonstrated a significant (P less than 0.01) decrease in arterial PO2 (mm. Hg) during the second and third weeks after exposure to black fly bites. Poults fed Clopidol (0.0125%) during the exposure period and subsequent experimental periods showed very little parasitemia and no significant reduction in arterial PO2."}
{"id": "PMID:241067", "title": "The pharmacology of new ethylenediamine derivatives (ROM-126, ROM-131, MK-142) with antiarrhythmic action. Part I. General pharmacological properties.", "content": "Mentioned compounds, studied on several species of animals, decrease blood pressure and the heart rate, modify catecholamine-induced effects, show properties characteristic for the beta-receptor blocking agents. The stated differences being due mainly to the power of their action. These compounds possess also spasmolytic and locally anaesthetic action of various degrees. Only ROM-131 has antihistamine action.", "contents": "The pharmacology of new ethylenediamine derivatives (ROM-126, ROM-131, MK-142) with antiarrhythmic action. Part I. General pharmacological properties. Mentioned compounds, studied on several species of animals, decrease blood pressure and the heart rate, modify catecholamine-induced effects, show properties characteristic for the beta-receptor blocking agents. The stated differences being due mainly to the power of their action. These compounds possess also spasmolytic and locally anaesthetic action of various degrees. Only ROM-131 has antihistamine action."}
{"id": "PMID:241074", "title": "Extraction of Renilla-type luciferin from the calcium-activated photoproteins aequorin, mnemiopsin, and berovin.", "content": "Photoproteins, which emit light in an oxygen-independent intramolecular reaction initiated by calcium ions, have been isolated from several bioluminescent organisms, including the hydrozoan jellyfish Aequorea and the ctenophore Mnemiopsis. The system of a related anthozoan coelenterate, the sea pansy Renilla reniformis, however, is oxygen dependent, requiring two organic components, luciferin and luciferase. Previously published indirect evidence indicates that photoproteins may contain a Renilla-type luciferin. We have now extracted in high yield a Renilla-type luciferin from three photoproteins, aequorin (45% yield), mnemiopsin (98% yield), and berovin (85% yield). Photoprotein luciferin, released from the holoprotein by mercaptoethanol treatment and separated from apo-photoprotein by gel filtration, no longer responds to calcium but now requires luciferase and O2 for light production. Photoprotein luciferin is identical to Renilla luciferin with respect to reaction kinetics and bioluminescence spectral distribution. In view of these results, the generally accepted hypothesis that the photoprotein chromophore is a protein-stabilized hydroperoxide of luciferin must be modified. We believe, instead, that the chromophore is free luciferin and that oxygen is bound as an oxygenated derivative of an amino-acid side chain of the protein. We propose the general term \"coelenterate luciferin\" to describe the light-producing chromophore from all bioluminescent coelenterates and ctenophores.", "contents": "Extraction of Renilla-type luciferin from the calcium-activated photoproteins aequorin, mnemiopsin, and berovin. Photoproteins, which emit light in an oxygen-independent intramolecular reaction initiated by calcium ions, have been isolated from several bioluminescent organisms, including the hydrozoan jellyfish Aequorea and the ctenophore Mnemiopsis. The system of a related anthozoan coelenterate, the sea pansy Renilla reniformis, however, is oxygen dependent, requiring two organic components, luciferin and luciferase. Previously published indirect evidence indicates that photoproteins may contain a Renilla-type luciferin. We have now extracted in high yield a Renilla-type luciferin from three photoproteins, aequorin (45% yield), mnemiopsin (98% yield), and berovin (85% yield). Photoprotein luciferin, released from the holoprotein by mercaptoethanol treatment and separated from apo-photoprotein by gel filtration, no longer responds to calcium but now requires luciferase and O2 for light production. Photoprotein luciferin is identical to Renilla luciferin with respect to reaction kinetics and bioluminescence spectral distribution. In view of these results, the generally accepted hypothesis that the photoprotein chromophore is a protein-stabilized hydroperoxide of luciferin must be modified. We believe, instead, that the chromophore is free luciferin and that oxygen is bound as an oxygenated derivative of an amino-acid side chain of the protein. We propose the general term \"coelenterate luciferin\" to describe the light-producing chromophore from all bioluminescent coelenterates and ctenophores."}
{"id": "PMID:241075", "title": "Crosslinking and labeling of membrane proteins by transglutaminase-catalyzed reactions.", "content": "Transglutaminase enzymes catalyze for the formation of epsilon(gamma-glutamyl)lysyl crosslinks, or the substitution of a variety of primary amines for the amide function of protein-bound glutaminyl residues. These enzymes should therefore be useful in crosslinking the proteins of membranes and in attaching a variety of chemical probes and labels to these proteins. This usefulness is demonstrated in experiments with the enzyme liver transglutaminase and the membranes with the enzyme liver transglutaminase and the membranes of mouse erythrocytes and of rabbit skeletal muscle sarcoplasmic reticulum.", "contents": "Crosslinking and labeling of membrane proteins by transglutaminase-catalyzed reactions. Transglutaminase enzymes catalyze for the formation of epsilon(gamma-glutamyl)lysyl crosslinks, or the substitution of a variety of primary amines for the amide function of protein-bound glutaminyl residues. These enzymes should therefore be useful in crosslinking the proteins of membranes and in attaching a variety of chemical probes and labels to these proteins. This usefulness is demonstrated in experiments with the enzyme liver transglutaminase and the membranes with the enzyme liver transglutaminase and the membranes of mouse erythrocytes and of rabbit skeletal muscle sarcoplasmic reticulum."}
{"id": "PMID:241076", "title": "Functional arginyl residues as ATP binding sites of glutamine synthetase and carbamyl phosphate synthetase.", "content": "The reaction of phenylglyoxal with two enzymes in which ATP plays a complex role has been studied. Both ovine brain glutamine synthetase and Escherichia coli carbamyl phosphate synthetase [carbamoyl-phosphate synthase (glutamine); ATP:carbamate phosphotransferase (dephosphorylating, amido-transferring); EC 2.7.2.9]were inactivated by phenylglyoxal. The specificity of this reagent for arginyl residues of the two proteins was confirmed by amino acid analysis. ATP, but not the other substrates, protected these enzymes against inactivation by phenylglyoxal. Carbamyl phosphate synthetase was also protected by IMP and ornithine, positive allosteric effectors that alter the enzymatic activity be increasing the affinity for ATP. UMP, a negative allosteric effector that decreases the affinity for ATP, did not protect against inactivation. Differential labeling experiments with [14C]phenylglyoxal showed that the number of arginyl residues protected by ATP corresponded quite well to the known number of ATP catalytic sites for each protein. These data indicate that arginyl residues at the active sites of glutamine synthetase and carbamyl phosphate synthetase are involved in the binding of ATP. This phenylglyoxal inactivation study also provided information about the mechanistic role of ATP in the two synthetases. The data obtained on glutamine synthetase support the theory that ATP is attached to the enzyme as a portion of the catalytic site, and that its presence is essential for the binding of glutamate and glutamine. The data obtained on carbamyl phosphate synthetase are consistent with the previous proposal that carbonyl phosphate is an intermediate in the ATP-dependent activation of bicarbonate by this enzyme. It is also of interest that, with both glutamine synthetase and carbamyl phosphate synthetase, only a small portion of the total arginyl population of these enzymes reacted with phenylglyoxal. A summary of previous studies on the modification of enzyme arginyl residues is presented.", "contents": "Functional arginyl residues as ATP binding sites of glutamine synthetase and carbamyl phosphate synthetase. The reaction of phenylglyoxal with two enzymes in which ATP plays a complex role has been studied. Both ovine brain glutamine synthetase and Escherichia coli carbamyl phosphate synthetase [carbamoyl-phosphate synthase (glutamine); ATP:carbamate phosphotransferase (dephosphorylating, amido-transferring); EC 2.7.2.9]were inactivated by phenylglyoxal. The specificity of this reagent for arginyl residues of the two proteins was confirmed by amino acid analysis. ATP, but not the other substrates, protected these enzymes against inactivation by phenylglyoxal. Carbamyl phosphate synthetase was also protected by IMP and ornithine, positive allosteric effectors that alter the enzymatic activity be increasing the affinity for ATP. UMP, a negative allosteric effector that decreases the affinity for ATP, did not protect against inactivation. Differential labeling experiments with [14C]phenylglyoxal showed that the number of arginyl residues protected by ATP corresponded quite well to the known number of ATP catalytic sites for each protein. These data indicate that arginyl residues at the active sites of glutamine synthetase and carbamyl phosphate synthetase are involved in the binding of ATP. This phenylglyoxal inactivation study also provided information about the mechanistic role of ATP in the two synthetases. The data obtained on glutamine synthetase support the theory that ATP is attached to the enzyme as a portion of the catalytic site, and that its presence is essential for the binding of glutamate and glutamine. The data obtained on carbamyl phosphate synthetase are consistent with the previous proposal that carbonyl phosphate is an intermediate in the ATP-dependent activation of bicarbonate by this enzyme. It is also of interest that, with both glutamine synthetase and carbamyl phosphate synthetase, only a small portion of the total arginyl population of these enzymes reacted with phenylglyoxal. A summary of previous studies on the modification of enzyme arginyl residues is presented."}
{"id": "PMID:241077", "title": "An octamer of histones in chromatin and free in solution.", "content": "Crosslinking with dimethyl suberimidate reveals a chain of histone octamers in chromatin. The octamer can be isolated free in solution at high ionic strength and pH. The identification of dimers formed by crosslinking reveals two or more contacts of each histone with others within the octamer. The molecular weight (110,000) and pattern of dissociation of the octamer are compatible with the composition (F2A1)2(F3)2(F2A2)2(F2B)2.", "contents": "An octamer of histones in chromatin and free in solution. Crosslinking with dimethyl suberimidate reveals a chain of histone octamers in chromatin. The octamer can be isolated free in solution at high ionic strength and pH. The identification of dimers formed by crosslinking reveals two or more contacts of each histone with others within the octamer. The molecular weight (110,000) and pattern of dissociation of the octamer are compatible with the composition (F2A1)2(F3)2(F2A2)2(F2B)2."}
{"id": "PMID:241078", "title": "Influence of alterations in meal frequency on lipogenesis and body fat content in the rat.", "content": "Rats were allowed to eat only 2 hr per day (meal-fed) or were fed ad libitum (nibbler) for 12 wk; another group of animals was meal-fed for 3 wk and then fed ad libitum (converted I) while the fourth group of rats (converted II) was meal-fed for 3 wk, allowed to nibble for the next 3 wk, meal-fed from the 6th to 9th wk and then returned to ad libitum feeding for the last 3 wk. Body fat gain and food efficiency was increased in converted I rats. The lipogenic capacity of adipose tissue from meal-fed rats was greater than observen meal-fed rats were reverted to ad libitum feeding whereas lipogenic activity increased rapidly when ad libitum fed rats were switched to meal-feeding.", "contents": "Influence of alterations in meal frequency on lipogenesis and body fat content in the rat. Rats were allowed to eat only 2 hr per day (meal-fed) or were fed ad libitum (nibbler) for 12 wk; another group of animals was meal-fed for 3 wk and then fed ad libitum (converted I) while the fourth group of rats (converted II) was meal-fed for 3 wk, allowed to nibble for the next 3 wk, meal-fed from the 6th to 9th wk and then returned to ad libitum feeding for the last 3 wk. Body fat gain and food efficiency was increased in converted I rats. The lipogenic capacity of adipose tissue from meal-fed rats was greater than observen meal-fed rats were reverted to ad libitum feeding whereas lipogenic activity increased rapidly when ad libitum fed rats were switched to meal-feeding."}
{"id": "PMID:241079", "title": "Methodological studies on the uptake of zinc by 3T3 cells.", "content": "In the present work, experiments were conducted on the uptake of zinc by 3T3 cells. (1) The percent Zn uptake gradually decreased with addition of increasing amount of zinc (0.05-8.4 mug). (2) With the increase of the incubation period from 2 to 16 hr, Zn uptake by nearly confluent cells increases gradually; however, confluent cells which are newly replated show a distinct cyclic increase in the Zn uptake after 2, 6, and 10 hr. (3) The amino acids of DMM and serum decrease Zn uptake. (4) Histidine at a molar excess of 1:50, 1:500, and 1:5000 reduces Zn uptake in comparison to a treatment with 65Zn-Zn-L-hist2 at a molar ratio of 1:5. (5) When zinc is added in the form of different Zn compounds, at a molar ratio of 1:2 or 1:1 (Zn:ligand), EDTA decreases the Zn uptake markedly. A small influence was shown also by albumin and histidine; however, other amino and organic acids at a molar ratio of 1:2 did not alter Zn uptake significantly.", "contents": "Methodological studies on the uptake of zinc by 3T3 cells. In the present work, experiments were conducted on the uptake of zinc by 3T3 cells. (1) The percent Zn uptake gradually decreased with addition of increasing amount of zinc (0.05-8.4 mug). (2) With the increase of the incubation period from 2 to 16 hr, Zn uptake by nearly confluent cells increases gradually; however, confluent cells which are newly replated show a distinct cyclic increase in the Zn uptake after 2, 6, and 10 hr. (3) The amino acids of DMM and serum decrease Zn uptake. (4) Histidine at a molar excess of 1:50, 1:500, and 1:5000 reduces Zn uptake in comparison to a treatment with 65Zn-Zn-L-hist2 at a molar ratio of 1:5. (5) When zinc is added in the form of different Zn compounds, at a molar ratio of 1:2 or 1:1 (Zn:ligand), EDTA decreases the Zn uptake markedly. A small influence was shown also by albumin and histidine; however, other amino and organic acids at a molar ratio of 1:2 did not alter Zn uptake significantly."}
{"id": "PMID:241080", "title": "Sodium urate accelerates precipitation of calcium oxalate in vitro.", "content": "Precipitation of calcium oxalate crystals from a metastable solution can be detected within 10 min if crystalline sodium urate is added at a solid to liquid ratio of 0.1 mM or more. Without urate, precipitation begins after 50 min. Uric acid is not effective. Pyrophosphate inhibits the effects of sodium urate.", "contents": "Sodium urate accelerates precipitation of calcium oxalate in vitro. Precipitation of calcium oxalate crystals from a metastable solution can be detected within 10 min if crystalline sodium urate is added at a solid to liquid ratio of 0.1 mM or more. Without urate, precipitation begins after 50 min. Uric acid is not effective. Pyrophosphate inhibits the effects of sodium urate."}
{"id": "PMID:241081", "title": "Heterogeneous nucleation of calcium oxalate by seeds of monosodium urate.", "content": "Seeds of monosodium urate caused heterogeneous nucleation of calcium oxalate at pH 5.7 and 6.7, and of calcium phosphate at pH 5.3, 5.7, and 6.7 from metastably supersaturated solutions in vitro. Seeds of uric acid had a small or no effect. The results could account for the formation of calcium stones among patients with hyperuricosuria and normocalciuria.", "contents": "Heterogeneous nucleation of calcium oxalate by seeds of monosodium urate. Seeds of monosodium urate caused heterogeneous nucleation of calcium oxalate at pH 5.7 and 6.7, and of calcium phosphate at pH 5.3, 5.7, and 6.7 from metastably supersaturated solutions in vitro. Seeds of uric acid had a small or no effect. The results could account for the formation of calcium stones among patients with hyperuricosuria and normocalciuria."}
{"id": "PMID:241082", "title": "Effects of ganglionic and beta-adrenergic blockade on cardiovascular responses to the bisenoic prostaglandins and their precursor arachidonic acid.", "content": "Arachidonic acid (AA) 300 mug/kg, and PGE2, 5 mug/kg consistently produced a decrease in systemic arterial pressure in anesthetized dogs. PGF2alpha, 5 mug/kg, produced a pressor response. All three compounds increased myocardial contractile force, but the magnitude of the change following AA was less prominent. After ganglionic blockade, the depressor response to AA and PGE2 persisted and the pressor response to PGF2alpha was augmented. Myocardial contractile force did not increase following AA in ganglion-blocked animals indicating that the cardiac responses observed before hexamethonium were mediated by the baroreceptor reflexes. A much larger dose of AA (900 mug/kg) resulted in a small positive inotropic effect on the heart. This possibly represents a direct cardiac effect of AA, or may be indicative of increased biosynthesis of an intermediate endoperoxide, or PGE2 and PGF2alpha. Both PGE2 and PGF2alpha have a direct positive inotropic effect on the heart. The persist cardiac effects of PGE2 and PGF2 after beta-adrenergic blockade suggests that these compounds may not interact with the beta-receptors of the myocardium.", "contents": "Effects of ganglionic and beta-adrenergic blockade on cardiovascular responses to the bisenoic prostaglandins and their precursor arachidonic acid. Arachidonic acid (AA) 300 mug/kg, and PGE2, 5 mug/kg consistently produced a decrease in systemic arterial pressure in anesthetized dogs. PGF2alpha, 5 mug/kg, produced a pressor response. All three compounds increased myocardial contractile force, but the magnitude of the change following AA was less prominent. After ganglionic blockade, the depressor response to AA and PGE2 persisted and the pressor response to PGF2alpha was augmented. Myocardial contractile force did not increase following AA in ganglion-blocked animals indicating that the cardiac responses observed before hexamethonium were mediated by the baroreceptor reflexes. A much larger dose of AA (900 mug/kg) resulted in a small positive inotropic effect on the heart. This possibly represents a direct cardiac effect of AA, or may be indicative of increased biosynthesis of an intermediate endoperoxide, or PGE2 and PGF2alpha. Both PGE2 and PGF2alpha have a direct positive inotropic effect on the heart. The persist cardiac effects of PGE2 and PGF2 after beta-adrenergic blockade suggests that these compounds may not interact with the beta-receptors of the myocardium."}
{"id": "PMID:241083", "title": "Hemodynamic effects of procainamide and quinidine and the influence of beta-blockade before and after experimental myocardial infarction.", "content": "The use of antiarrhythmie drugs in combination has been limited because of possible side effects secondary to myocardial depression in the acute myocardial infarction patient. Therefore, we investigated in intact dogs (group I) the hemodynamic interaction of propranolol plus procainamide (subgroup A) or quinidine (subgroup B) and in dogs after experimental myocardial infarction produced by coronary artery ligation (group II). Infusion of procainamide (30 mg/kg over 5 min) in animals of group IA produced a significant (P less than 0.05) decrease of 30% in mean aortic pressure, a decrease of 40% in left ventricular dp/dt and 29% in cardiac output. When procainamide was reinfuse after propranolol (1 mg/kg), its hemodynamic effects were not significantly different from those observed before propranolol in both groups IA and IIA. Infusion of quinidine (10 mg/kg over 5 min) in animals of group IB (intact dogs) also produced significant decreases of 24% in mean aortic pressure and 38% in dp/dt while cardiac output was unchanged. However, these hemodynamic changes were seen only after beta-blockade and were significantly different from those obtained before propranolol, where heart rate increased by 14%, dp/dt by 30%, and cardiac output by 35%. These changes occurred despite a similar reduction in mean aortic pressure. This drug combination produced similar response in animals after coronary artery ligation (group IIB). In conclusion, we feel that the administration of propranolol does not prevent the depressive circulatory effects of procainamide. The combined use of quinidine and propranolol also has a negative circulatory effect although not as marked as the effects observed after procainamide with propranolol.", "contents": "Hemodynamic effects of procainamide and quinidine and the influence of beta-blockade before and after experimental myocardial infarction. The use of antiarrhythmie drugs in combination has been limited because of possible side effects secondary to myocardial depression in the acute myocardial infarction patient. Therefore, we investigated in intact dogs (group I) the hemodynamic interaction of propranolol plus procainamide (subgroup A) or quinidine (subgroup B) and in dogs after experimental myocardial infarction produced by coronary artery ligation (group II). Infusion of procainamide (30 mg/kg over 5 min) in animals of group IA produced a significant (P less than 0.05) decrease of 30% in mean aortic pressure, a decrease of 40% in left ventricular dp/dt and 29% in cardiac output. When procainamide was reinfuse after propranolol (1 mg/kg), its hemodynamic effects were not significantly different from those observed before propranolol in both groups IA and IIA. Infusion of quinidine (10 mg/kg over 5 min) in animals of group IB (intact dogs) also produced significant decreases of 24% in mean aortic pressure and 38% in dp/dt while cardiac output was unchanged. However, these hemodynamic changes were seen only after beta-blockade and were significantly different from those obtained before propranolol, where heart rate increased by 14%, dp/dt by 30%, and cardiac output by 35%. These changes occurred despite a similar reduction in mean aortic pressure. This drug combination produced similar response in animals after coronary artery ligation (group IIB). In conclusion, we feel that the administration of propranolol does not prevent the depressive circulatory effects of procainamide. The combined use of quinidine and propranolol also has a negative circulatory effect although not as marked as the effects observed after procainamide with propranolol."}
{"id": "PMID:241084", "title": "Organ-specific DNA damage induced in mice by the organotropic carcinogens 4-nitroquinoline 1-oxide and dimethylnitrosamine.", "content": "The extent of DNA fragmentation induced in lung, kidney, and liver of mice injected with the chemical carcinogens 4-nitroquinoline 1-oxide (4NQO), dimethylnitrosamine (DMN) and the noncarcinogenic 4-aminoquinoline 1-oxide (4AQO) was estimated by the alkaline sucrose gradient technique. A floating of minced lung tissue pieces in the alkaline lysing solution on top of the gradients afforded a gentle method of lung DNA extraction. This technique minimized mechanical shearing of lung DNA and permitted comparisons to be made with liver and kidney DNA sedimentation patterns. The extent of DNA damage induced by 4NQO followed the order: lung, kidney, liver, while that induced by DMN followed the order: liver, kidney, lung. The sites of greatest DNA damage appeared to correlate with sites of high levels of DNA repair synthesis and the sites of tumor induction. No DNA damage was induced by the noncarcinogenic 4-aminoquinoline 1-oxide (4AQO).", "contents": "Organ-specific DNA damage induced in mice by the organotropic carcinogens 4-nitroquinoline 1-oxide and dimethylnitrosamine. The extent of DNA fragmentation induced in lung, kidney, and liver of mice injected with the chemical carcinogens 4-nitroquinoline 1-oxide (4NQO), dimethylnitrosamine (DMN) and the noncarcinogenic 4-aminoquinoline 1-oxide (4AQO) was estimated by the alkaline sucrose gradient technique. A floating of minced lung tissue pieces in the alkaline lysing solution on top of the gradients afforded a gentle method of lung DNA extraction. This technique minimized mechanical shearing of lung DNA and permitted comparisons to be made with liver and kidney DNA sedimentation patterns. The extent of DNA damage induced by 4NQO followed the order: lung, kidney, liver, while that induced by DMN followed the order: liver, kidney, lung. The sites of greatest DNA damage appeared to correlate with sites of high levels of DNA repair synthesis and the sites of tumor induction. No DNA damage was induced by the noncarcinogenic 4-aminoquinoline 1-oxide (4AQO)."}
{"id": "PMID:241085", "title": "Oxidation-reduction potentials in the cecal contents of rats and mice.", "content": "The oxidation-reduction potential (ORP) in the cecal contents of conventional rats, germ-free mice, and mice with a Colonization Resistance Factor flora (CRF-mice) was investigated. By using animals that were anaesthetized for a longer period of time, we attempted to eliminate the disturbing influence of oxygen. In addition, measurements were made under anaerobic conditions. For the rats, the ORP values reached a more or less constant level after about 30 min following the insertion of the electrodes. The mean ORP at that time was -458 mV (SD = 45 mV). The mean ORP values for the mice showed a more gradual reduction than was found in the rats. The curves leveled off at about 100 min following the insertion of the electrodes. The mean ORP values 100 min after electrode insertion were: germ-free mice, + 3 mV (SD = 39 mV); CRF-mice, -554 mV (SD = 29 mV). In rats, the ORP value decreased after death; no decrease was observed in mice. No difference was found in the values obtained when measuring under anaerobic or aerobic conditions after death.", "contents": "Oxidation-reduction potentials in the cecal contents of rats and mice. The oxidation-reduction potential (ORP) in the cecal contents of conventional rats, germ-free mice, and mice with a Colonization Resistance Factor flora (CRF-mice) was investigated. By using animals that were anaesthetized for a longer period of time, we attempted to eliminate the disturbing influence of oxygen. In addition, measurements were made under anaerobic conditions. For the rats, the ORP values reached a more or less constant level after about 30 min following the insertion of the electrodes. The mean ORP at that time was -458 mV (SD = 45 mV). The mean ORP values for the mice showed a more gradual reduction than was found in the rats. The curves leveled off at about 100 min following the insertion of the electrodes. The mean ORP values 100 min after electrode insertion were: germ-free mice, + 3 mV (SD = 39 mV); CRF-mice, -554 mV (SD = 29 mV). In rats, the ORP value decreased after death; no decrease was observed in mice. No difference was found in the values obtained when measuring under anaerobic or aerobic conditions after death."}
{"id": "PMID:241091", "title": "Application of Gran's potentiometric method in pharmaceutical analysis.", "content": "Because of weak acid-base properties, many pharmaceuticals cannot be determined by the convenient neutralization titrimetric method. It is shown that such substances can be precisely analyzed by applying the graphic pH-potentiometric method of Gran. Some water-soluble and insoluble pharmaceuticals, which usually are analyzed in nonaqueous solvents, have been determined precisely in water solution by this method. The latter is also applied successfully to the analysis of mixtures and impurities in pharmaceuticals.", "contents": "Application of Gran's potentiometric method in pharmaceutical analysis. Because of weak acid-base properties, many pharmaceuticals cannot be determined by the convenient neutralization titrimetric method. It is shown that such substances can be precisely analyzed by applying the graphic pH-potentiometric method of Gran. Some water-soluble and insoluble pharmaceuticals, which usually are analyzed in nonaqueous solvents, have been determined precisely in water solution by this method. The latter is also applied successfully to the analysis of mixtures and impurities in pharmaceuticals."}
{"id": "PMID:241093", "title": "Factors related to the cariogenic potential of breakfast cereals.", "content": "Reported is a series of studies in which several breakfast cereals were tested for the following properties: sugar retained by, and plaque formed on, extracted teeth that chewed the cereals: ability of the cereals to induce acid formation when incubated with saliva and to neutralize acids when mixed with water: and, as a summary, ability to induce caries formation under mouth-simulation conditions. It was found that the cariogenic potential of the cereals tested is not dependent upon their sugar content, their retentiveness on the teeth, the amount of sugar retained by the teeth, or the amount of plaque formation they induced on the teeth. The only parameter that related well with the carcinogenic potential of the cereals was their buffering (or acid-neutralizing) ability: the greater the buffering, the lesser the carcinogenic potential. These results, which were confirmed in independent animal studies, case some doubts upon the role traditionally attributed to sugars in caries formation. At least they caution against generalizations and point out other factors that should be studied before a thorough understanding of the factors determining the cariogenicity of foods can be gained.", "contents": "Factors related to the cariogenic potential of breakfast cereals. Reported is a series of studies in which several breakfast cereals were tested for the following properties: sugar retained by, and plaque formed on, extracted teeth that chewed the cereals: ability of the cereals to induce acid formation when incubated with saliva and to neutralize acids when mixed with water: and, as a summary, ability to induce caries formation under mouth-simulation conditions. It was found that the cariogenic potential of the cereals tested is not dependent upon their sugar content, their retentiveness on the teeth, the amount of sugar retained by the teeth, or the amount of plaque formation they induced on the teeth. The only parameter that related well with the carcinogenic potential of the cereals was their buffering (or acid-neutralizing) ability: the greater the buffering, the lesser the carcinogenic potential. These results, which were confirmed in independent animal studies, case some doubts upon the role traditionally attributed to sugars in caries formation. At least they caution against generalizations and point out other factors that should be studied before a thorough understanding of the factors determining the cariogenicity of foods can be gained."}
{"id": "PMID:241097", "title": "Prostaglandin-E2-9-ketoreductase in rabbit kidney.", "content": "The 100,000 xg supernatant of rabbit kidney contains a prostaglandin-E2-9-ketoreductase which has an obligatory requirement for NADPH. This enzyme is localised in the renal cortex and is able to quantitatively convert PGE2 to PGF2alpha. A broad pH profile was evident with an optimum at pH 7 with 5. Kinetic studies indicated a Km of 3 with 2 x 10-4M PGE2. The isoelectric point was at pH 5 with 65 and the molecular weight, as estimated by gel filtration, was 21,800. These values differ from those obtained with enzyme from monkey brain tissue and suggest a tissue specificity of PGE2-9-ketoreductase. By combining isoelectric focussing techniques with sephadex filtration considerable purification of the renal enzyme was achieved.", "contents": "Prostaglandin-E2-9-ketoreductase in rabbit kidney. The 100,000 xg supernatant of rabbit kidney contains a prostaglandin-E2-9-ketoreductase which has an obligatory requirement for NADPH. This enzyme is localised in the renal cortex and is able to quantitatively convert PGE2 to PGF2alpha. A broad pH profile was evident with an optimum at pH 7 with 5. Kinetic studies indicated a Km of 3 with 2 x 10-4M PGE2. The isoelectric point was at pH 5 with 65 and the molecular weight, as estimated by gel filtration, was 21,800. These values differ from those obtained with enzyme from monkey brain tissue and suggest a tissue specificity of PGE2-9-ketoreductase. By combining isoelectric focussing techniques with sephadex filtration considerable purification of the renal enzyme was achieved."}
{"id": "PMID:241098", "title": "Interactions of adrenergic stimulants and blockers on self-stimulation behavior in rats.", "content": "Self-stimulation behavior in rats was facilitated by two adrenergic stimulants, amphetamine (0.5 or 1 mg/kg, intraperitoneal, i.p., or 100 mug, intracerebroventricular, i.c.v.) and cocaine (5 mg/kg, i.p.). Three alpha-adrenergic blockers (phenoxybenzamine, dibenamine, phentolamine) and a beta-adrenergic blocker (propranolol) decreased self-stimulation responding at 100 mug i.c.v. doses, but showed very little effect at small i.p. doses. Pretreatment with alpha- and beta-adrenergic blockers (i.c.v.) also decreased amphetamine-facilitated responding. The effects of amphetamine or cocaine (i.p.) were not significantly altered by these blockers at the doses used. The depressant effects of the alpha- and beta-adrenergic blockers on self-stimulation behavior appear to be nonspecific with respect to the type of adrenergic receptors.", "contents": "Interactions of adrenergic stimulants and blockers on self-stimulation behavior in rats. Self-stimulation behavior in rats was facilitated by two adrenergic stimulants, amphetamine (0.5 or 1 mg/kg, intraperitoneal, i.p., or 100 mug, intracerebroventricular, i.c.v.) and cocaine (5 mg/kg, i.p.). Three alpha-adrenergic blockers (phenoxybenzamine, dibenamine, phentolamine) and a beta-adrenergic blocker (propranolol) decreased self-stimulation responding at 100 mug i.c.v. doses, but showed very little effect at small i.p. doses. Pretreatment with alpha- and beta-adrenergic blockers (i.c.v.) also decreased amphetamine-facilitated responding. The effects of amphetamine or cocaine (i.p.) were not significantly altered by these blockers at the doses used. The depressant effects of the alpha- and beta-adrenergic blockers on self-stimulation behavior appear to be nonspecific with respect to the type of adrenergic receptors."}
{"id": "PMID:241099", "title": "The effect of various doses of minor tranquilizers on plasma corticosteroids in stressed rats.", "content": "Minor tranquilizers have been shown to be specific inhibitors of the elevation of plasma corticosteroid levels in rats subjected to mild stress. The inability of several anxiolytic compounds to show activity at high doses prompted an investigation of the effect on corticosteroid levels of these drugs over a wider dosage range. It was found that at high doses, the drugs themselves cause an elevation of corticosteroid levels masking the blocking of the stress-induced elevations. It was discovered that upon sub-chronic administration, the drug-induced elevation diminishes while the ability to inhibit stress-induced elevation persists. Finally, an extensive dose response curve for phenobarbital demonstrated a variety of responses, depending upon the dose; an antistress effect at low dose, a relatively ineffective dose range from 50-100 mg/kg, and a corticosteroid lowering effect at anesthetic doses. The lack of effect of moderately high doses has been explained through their depressant side effects, which in themselves are stressful to the animal.", "contents": "The effect of various doses of minor tranquilizers on plasma corticosteroids in stressed rats. Minor tranquilizers have been shown to be specific inhibitors of the elevation of plasma corticosteroid levels in rats subjected to mild stress. The inability of several anxiolytic compounds to show activity at high doses prompted an investigation of the effect on corticosteroid levels of these drugs over a wider dosage range. It was found that at high doses, the drugs themselves cause an elevation of corticosteroid levels masking the blocking of the stress-induced elevations. It was discovered that upon sub-chronic administration, the drug-induced elevation diminishes while the ability to inhibit stress-induced elevation persists. Finally, an extensive dose response curve for phenobarbital demonstrated a variety of responses, depending upon the dose; an antistress effect at low dose, a relatively ineffective dose range from 50-100 mg/kg, and a corticosteroid lowering effect at anesthetic doses. The lack of effect of moderately high doses has been explained through their depressant side effects, which in themselves are stressful to the animal."}
{"id": "PMID:241100", "title": "Interaction of psychoactive drugs with the Mg+2 requiring ATPase associated with isolated synaptic vesicles.", "content": "A large series of CNS active drugs have been tested for their possible effect on the Mg+2 dependent ATPase associated with isolated synaptic vesicles. Antipsychotic agents and cocaine showed inhibition, of a non-competitive type. The implications of this finding for a synaptic theory of psychosis are discussed.", "contents": "Interaction of psychoactive drugs with the Mg+2 requiring ATPase associated with isolated synaptic vesicles. A large series of CNS active drugs have been tested for their possible effect on the Mg+2 dependent ATPase associated with isolated synaptic vesicles. Antipsychotic agents and cocaine showed inhibition, of a non-competitive type. The implications of this finding for a synaptic theory of psychosis are discussed."}
{"id": "PMID:241101", "title": "Inhibitory effect of anti-obesity drugs on NADH dehydrogenase of mouse heart homogenates.", "content": "Propylhexedrine and chlorphentermine inhibit the activity of NADH cytochrome c reductase but to a lesser extent than fenfluramine. Diethylpropion and phendimetrazine have little effect.", "contents": "Inhibitory effect of anti-obesity drugs on NADH dehydrogenase of mouse heart homogenates. Propylhexedrine and chlorphentermine inhibit the activity of NADH cytochrome c reductase but to a lesser extent than fenfluramine. Diethylpropion and phendimetrazine have little effect."}
{"id": "PMID:241102", "title": "Antagonism of fenoterol against beta-blocking drugs bunitrolol and practolol in asthmatics.", "content": "In 4 X 10 young white male histamine-sensitive asthmatics without bronchitis or emphysema, the antagonism of fenoterol (40 mug) to bunitrolol (2.5 and 5 mg) or practolol (20 and 30 mg) was tested in an open comparative trial. Pulse frequency and several physiological parameters were determined before and after histamine challenge test, after injection of beta-blocking drug and after injection of fenotrolol. All groups were found to be equally sensitive to histamine. Bunitrolol and practolol were found to have no influence on histamine effect. It was also found that bunitrolol in the dosages tested is a much more potent beta-blocking drug in the bronchi compared to practolol in the dosages tested were equivalent. beta-Blockade of practolol (20 or 30 mg) could completely be antagonized by 40 mug fenoterol; this dosage was not sufficient to antagonize 2.5 or 5 mg bunitrolol.", "contents": "Antagonism of fenoterol against beta-blocking drugs bunitrolol and practolol in asthmatics. In 4 X 10 young white male histamine-sensitive asthmatics without bronchitis or emphysema, the antagonism of fenoterol (40 mug) to bunitrolol (2.5 and 5 mg) or practolol (20 and 30 mg) was tested in an open comparative trial. Pulse frequency and several physiological parameters were determined before and after histamine challenge test, after injection of beta-blocking drug and after injection of fenotrolol. All groups were found to be equally sensitive to histamine. Bunitrolol and practolol were found to have no influence on histamine effect. It was also found that bunitrolol in the dosages tested is a much more potent beta-blocking drug in the bronchi compared to practolol in the dosages tested were equivalent. beta-Blockade of practolol (20 or 30 mg) could completely be antagonized by 40 mug fenoterol; this dosage was not sufficient to antagonize 2.5 or 5 mg bunitrolol."}
{"id": "PMID:241103", "title": "A fish in extreme alkalinity.", "content": "Tilapia grahami (Boulenger), a small cichlid fish, inhabits extremely alkaline water where the total CO2 concentration exceeds 200 meq.L(-1), osmolality is about 600 mosm.L(-1), pH ranges between 9.6 and 10.5 and temperature may be 43 degrees C. Venous blood drawn anaerobically by heart puncture had pH values as high as 8.4 at 35 degrees C. A 10-15-fold bicarbonate concentration gradient exists across the gills of Tilapia. It is suggested that the uniquely high and variable blood pH results when blood in the gills are exposed to water in which free CO2 can hardly exist. Blood CO2 must be correspondingly low resulting in pH values hitherto unknown to occur in vertebrates.", "contents": "A fish in extreme alkalinity. Tilapia grahami (Boulenger), a small cichlid fish, inhabits extremely alkaline water where the total CO2 concentration exceeds 200 meq.L(-1), osmolality is about 600 mosm.L(-1), pH ranges between 9.6 and 10.5 and temperature may be 43 degrees C. Venous blood drawn anaerobically by heart puncture had pH values as high as 8.4 at 35 degrees C. A 10-15-fold bicarbonate concentration gradient exists across the gills of Tilapia. It is suggested that the uniquely high and variable blood pH results when blood in the gills are exposed to water in which free CO2 can hardly exist. Blood CO2 must be correspondingly low resulting in pH values hitherto unknown to occur in vertebrates."}
{"id": "PMID:241104", "title": "Factors controlling the in vitro and in vivo oxygen affinity of the hemocyanin in the crab Carcinus maenas (L.).", "content": "The oxygen affinity of the hemocyanin of the crab Carcinus maenas was studied in vitro by measuring the O2 partial pressure at 50% saturation, P50, at various conditions of pH, temperature and salt concentration. At alkaline pH, the hemocyanin exhibits a normal Bohr effect, inverted below pH=pH0=6.9 at 15 degrees C. A rise of temperature provokes an increase of both P50 and pH0. Within the physiological range, only Ca++ and Mg++ ions influence the oxygen affinity. Both ions decrease P50, and Mg++ increases the Bohr factor, deltalogP50/deltapH. The variations of P50 due to changes of pH, temperature (degrees C) and Ca++ and Mg++ concentrations (mEq-L-1) are satisfactorily described by the empirical quantitative expressions: see article. Long-term temperature adaptation of the animals results in changes of the parameter k' which appears to be dependent on the concentration of an unidentified dialysable substance in blood. As temperature rises, this phenomenon limits the in vivo increase of P50 induced by both the intrinsic temperature effect and the decrease of in vivo blood pH. When external salinity decreases, lower blood Ca++ and Mg++ concentrations entail an increase of P50, but without changes of k', an effect compensated for in vivo by an increase of the blood pH. The observations suggest that the functional oxygen affinity of the pigment is physiologically regulated to ensure an adequate oxygen transport by the blood in quite varied conditions of temperature and salinity.", "contents": "Factors controlling the in vitro and in vivo oxygen affinity of the hemocyanin in the crab Carcinus maenas (L.). The oxygen affinity of the hemocyanin of the crab Carcinus maenas was studied in vitro by measuring the O2 partial pressure at 50% saturation, P50, at various conditions of pH, temperature and salt concentration. At alkaline pH, the hemocyanin exhibits a normal Bohr effect, inverted below pH=pH0=6.9 at 15 degrees C. A rise of temperature provokes an increase of both P50 and pH0. Within the physiological range, only Ca++ and Mg++ ions influence the oxygen affinity. Both ions decrease P50, and Mg++ increases the Bohr factor, deltalogP50/deltapH. The variations of P50 due to changes of pH, temperature (degrees C) and Ca++ and Mg++ concentrations (mEq-L-1) are satisfactorily described by the empirical quantitative expressions: see article. Long-term temperature adaptation of the animals results in changes of the parameter k' which appears to be dependent on the concentration of an unidentified dialysable substance in blood. As temperature rises, this phenomenon limits the in vivo increase of P50 induced by both the intrinsic temperature effect and the decrease of in vivo blood pH. When external salinity decreases, lower blood Ca++ and Mg++ concentrations entail an increase of P50, but without changes of k', an effect compensated for in vivo by an increase of the blood pH. The observations suggest that the functional oxygen affinity of the pigment is physiologically regulated to ensure an adequate oxygen transport by the blood in quite varied conditions of temperature and salinity."}
{"id": "PMID:241105", "title": "Blood and CSF acid-base changes, and rate of ventilatory acclimatization of awake dogs to 3,550 m.", "content": "Awake, intact dogs trained to wear a respiratory mask were studied in a hypobaric chamber at 140 m and at various stages of a 4-week exposure to 3,550 m. Resting ventilation, pulmonary gas exchanges, arterial blood gases and pH, acid-base status of the cisternal fluid (CSF) and ventilatory responses to transient O2 inhalation were measured. Attention is focussed on the time course of ventilatory acclimatization to altitude, characterized by hyperventilation with hypocapnia and a consequent increase of arterial Po2. (1) 75 percent of the increment in pulmonary ventilation due to hypoxia was achieved in 30 minutes; (2) the further increase, 25 percent of the total hyperventilation, was complete after 3 hr, with a corresponding Pco2 drop and pH increase in blood and CSF, and an increase in Pao2; (3) the secondary increase in ventilation, beyond the acute exposure period, was not related to return of [H+] in CSF towards control value; (4) the large transient decrease of ventilation following brief oxygen inhalation demonstrated a strong arterial chemoreflex drive in acclimatized animals. The extremely rapid ventilatory acclimatization to moderately high altitude in normal dogs appears to be mediated not by CSF hydrogen ion concentration but by a strong chemoreflex drive of ventilation.", "contents": "Blood and CSF acid-base changes, and rate of ventilatory acclimatization of awake dogs to 3,550 m. Awake, intact dogs trained to wear a respiratory mask were studied in a hypobaric chamber at 140 m and at various stages of a 4-week exposure to 3,550 m. Resting ventilation, pulmonary gas exchanges, arterial blood gases and pH, acid-base status of the cisternal fluid (CSF) and ventilatory responses to transient O2 inhalation were measured. Attention is focussed on the time course of ventilatory acclimatization to altitude, characterized by hyperventilation with hypocapnia and a consequent increase of arterial Po2. (1) 75 percent of the increment in pulmonary ventilation due to hypoxia was achieved in 30 minutes; (2) the further increase, 25 percent of the total hyperventilation, was complete after 3 hr, with a corresponding Pco2 drop and pH increase in blood and CSF, and an increase in Pao2; (3) the secondary increase in ventilation, beyond the acute exposure period, was not related to return of [H+] in CSF towards control value; (4) the large transient decrease of ventilation following brief oxygen inhalation demonstrated a strong arterial chemoreflex drive in acclimatized animals. The extremely rapid ventilatory acclimatization to moderately high altitude in normal dogs appears to be mediated not by CSF hydrogen ion concentration but by a strong chemoreflex drive of ventilation."}
{"id": "PMID:241106", "title": "Electrochemical improvement of the performance of PO2 electrodes.", "content": "Rotating ring-disc electrode studies have indicated that relatively large quantities of hydrogen peroxide ion, HO2-, are produced when oxygen is reduced at a platinum or gold polarographic electrode surface. The electrochemical reduction processes are improved and the quantity of HO2- is reduced by using alkaline buffer electrolytes (pH 10 to 11) and by polarising the electrode at voltages more negative than -0.9 V. The presence of HO2- in the electrolyte has been shown to be the cause of excessively long time response in both blood-gas and respiratory polarographic PO2 electrodes; electrode alinearity on micro-blood-gas PO2 electrodes has also been shown to be due to the absence of a plateau on the polarogram of electrodes when used with conventional electrolytes. The use of a high pH buffer and high negative voltage results in a long, flat plateau and a marked improvement in both electrode linearity and response time. This two-fold improvement in electrode performance holds true for both platinum and gold polarographic respiratory gas and blood-gas PO2 electrodes.", "contents": "Electrochemical improvement of the performance of PO2 electrodes. Rotating ring-disc electrode studies have indicated that relatively large quantities of hydrogen peroxide ion, HO2-, are produced when oxygen is reduced at a platinum or gold polarographic electrode surface. The electrochemical reduction processes are improved and the quantity of HO2- is reduced by using alkaline buffer electrolytes (pH 10 to 11) and by polarising the electrode at voltages more negative than -0.9 V. The presence of HO2- in the electrolyte has been shown to be the cause of excessively long time response in both blood-gas and respiratory polarographic PO2 electrodes; electrode alinearity on micro-blood-gas PO2 electrodes has also been shown to be due to the absence of a plateau on the polarogram of electrodes when used with conventional electrolytes. The use of a high pH buffer and high negative voltage results in a long, flat plateau and a marked improvement in both electrode linearity and response time. This two-fold improvement in electrode performance holds true for both platinum and gold polarographic respiratory gas and blood-gas PO2 electrodes."}
{"id": "PMID:241107", "title": "Cerebrospinal fluid alkalosis during high-altitude sojourn in unanesthetized ponies.", "content": "Unanesthetized adult female ponies were studied near sea level (250 m) and during sojourns to 3400 m (N=6) and 4300 m (N=7) altitude. The pH, PCO2, and PO2 of arterial blood and pH and PCO2 of cerebrospinal fluid (CSF) were measured under conditions of acute (1 hr) and chronic (1-45 days) hypoxia. Cerebrospinal fluid was sampled from the cisterna magna of the awake pony and arterial blood withdrawn from an indwelling arterial catheter. In both groups of animals, PaCO2 decreased slightly after 1 hr of hypoxia (delta PaCO2= - 0.6 mm Hg at 3400 m; - 3.9 mm Hg at 4300 m), decreased further after 1-5 days at high altitude (delta PaCO2= - 7.2 mm Hg at 3400 m; - 12.3 mm Hg at 4300 m) and then increased significantly after 6 days of chronic hypoxia (delta PaCO2= + 4.1 mm Hg at 3400 m; + 4.7 mm Hg at 4300 m). Although PaO2 decreased markedly during acute hypoxia, subsequent changes in PaCO2 at high altitude did not alter PaO2 from that observed during acute hypoxia (PaO2=52 mm Hg at 3400 m; 41 mm Hg at 4300 m). The pH of CSF increased during acute hypoxia (delta pH= + 0.013 unit at 3400 m; + 0.033 unit at 4300 m) and became more alkaline after 1-2 days at high altitude (delta pH= + 0.031 unit at 3400 m; + 0.064 unit at 4300 m). At 4300 m, CSF pH remained alkaline to control values throughout sojourn. Under these conditions of chronic hypocapnic hypoxia, CSF pH was imperfectly regulated and regulated in a magnitude equal to (3400 m) or less than (4300 m) arterial blood. Furthermore, the similarity of relative changes in CSF [HCO3-] and arterial [HCO3-] during chronic hypoxia may indicate a passive regulation of CSF [HCO3-] rather than local 'CSF-specific' mechanisms as previously proposed.", "contents": "Cerebrospinal fluid alkalosis during high-altitude sojourn in unanesthetized ponies. Unanesthetized adult female ponies were studied near sea level (250 m) and during sojourns to 3400 m (N=6) and 4300 m (N=7) altitude. The pH, PCO2, and PO2 of arterial blood and pH and PCO2 of cerebrospinal fluid (CSF) were measured under conditions of acute (1 hr) and chronic (1-45 days) hypoxia. Cerebrospinal fluid was sampled from the cisterna magna of the awake pony and arterial blood withdrawn from an indwelling arterial catheter. In both groups of animals, PaCO2 decreased slightly after 1 hr of hypoxia (delta PaCO2= - 0.6 mm Hg at 3400 m; - 3.9 mm Hg at 4300 m), decreased further after 1-5 days at high altitude (delta PaCO2= - 7.2 mm Hg at 3400 m; - 12.3 mm Hg at 4300 m) and then increased significantly after 6 days of chronic hypoxia (delta PaCO2= + 4.1 mm Hg at 3400 m; + 4.7 mm Hg at 4300 m). Although PaO2 decreased markedly during acute hypoxia, subsequent changes in PaCO2 at high altitude did not alter PaO2 from that observed during acute hypoxia (PaO2=52 mm Hg at 3400 m; 41 mm Hg at 4300 m). The pH of CSF increased during acute hypoxia (delta pH= + 0.013 unit at 3400 m; + 0.033 unit at 4300 m) and became more alkaline after 1-2 days at high altitude (delta pH= + 0.031 unit at 3400 m; + 0.064 unit at 4300 m). At 4300 m, CSF pH remained alkaline to control values throughout sojourn. Under these conditions of chronic hypocapnic hypoxia, CSF pH was imperfectly regulated and regulated in a magnitude equal to (3400 m) or less than (4300 m) arterial blood. Furthermore, the similarity of relative changes in CSF [HCO3-] and arterial [HCO3-] during chronic hypoxia may indicate a passive regulation of CSF [HCO3-] rather than local 'CSF-specific' mechanisms as previously proposed."}
{"id": "PMID:241115", "title": "pH changes in dental plaque caused by sweetened, iron-containing liquid medicine.", "content": "Five commercially available liquid iron medicines and a 5% aqueous sucrose solution were tested in a randomized cross-over study with six subjects at intervals of 3-4 d. The pH in plaque was measured in minute samples taken 5 min before and 5, 10, 20, and 40 min after oral intake of 10-ml volumes of the test solutions. The iron-containing medicines differed with respecto to pH (2.8-7.0), buffer capacity, viscosity, and iron content; two contained sorbitol (28 and 42%) and three sucrose (9, 17, and 47%). As expected, all sucrose-containing preparations produced a significant decrease in pH while no appreciable pH changes followed those with sorbitol. The pH readings after 5 min were affected by the sucrose content rather than the initial pH of the solutions. The decrease in pH was of shorter duration after exposure to the sucrose-containing iron medicines than after the 50% aqueous sucrose solution.", "contents": "pH changes in dental plaque caused by sweetened, iron-containing liquid medicine. Five commercially available liquid iron medicines and a 5% aqueous sucrose solution were tested in a randomized cross-over study with six subjects at intervals of 3-4 d. The pH in plaque was measured in minute samples taken 5 min before and 5, 10, 20, and 40 min after oral intake of 10-ml volumes of the test solutions. The iron-containing medicines differed with respecto to pH (2.8-7.0), buffer capacity, viscosity, and iron content; two contained sorbitol (28 and 42%) and three sucrose (9, 17, and 47%). As expected, all sucrose-containing preparations produced a significant decrease in pH while no appreciable pH changes followed those with sorbitol. The pH readings after 5 min were affected by the sucrose content rather than the initial pH of the solutions. The decrease in pH was of shorter duration after exposure to the sucrose-containing iron medicines than after the 50% aqueous sucrose solution."}
{"id": "PMID:241116", "title": "Reduced capacity to produce specific 'effector' cells after injection of CBA mice with C3H cells.", "content": "Lymphocytes from mice of strain CBA are strongly MLC-responsive to lymphocytes from the H-2-compatible but M-antigen-incompatible strain C3H. This strong reactivity disappears after infusion of CBA mice with C3H lymphocytes. This study shows that the host-versus-graft reactivity (swelling of local lymph node after antigen injection) is specifically reduced after injection of CBA mice with C3H times CBA spleen cells. However, lymphocytes from such mice showed a specifically increased GVH reactivity (inhibition of erythroid cell growth) compared with lymphocytes from unimmunized mice. Lymphocytes from normal CBA mice showed a high proliferative rate in the spleens of irradiated C3H times CBA mice. Such 'educated' cells showed strongly increased specific GVH reactivity. Lymphocytes from CBA mice previously injected with C3H times CBA cells showed reduced capacity to proliferate when injected into irradiated C3H times CBA hybrids and a poor capacity to develop new 'effector' cells reactive against C3H times CBA bone marrow target cells. The results indicate that the presence of specifically 'MLC-responsive' lymphocytes in a lymphoid cell population is a prerequisite  of its production of 'effector' cells able to respond in this GVH assay.", "contents": "Reduced capacity to produce specific 'effector' cells after injection of CBA mice with C3H cells. Lymphocytes from mice of strain CBA are strongly MLC-responsive to lymphocytes from the H-2-compatible but M-antigen-incompatible strain C3H. This strong reactivity disappears after infusion of CBA mice with C3H lymphocytes. This study shows that the host-versus-graft reactivity (swelling of local lymph node after antigen injection) is specifically reduced after injection of CBA mice with C3H times CBA spleen cells. However, lymphocytes from such mice showed a specifically increased GVH reactivity (inhibition of erythroid cell growth) compared with lymphocytes from unimmunized mice. Lymphocytes from normal CBA mice showed a high proliferative rate in the spleens of irradiated C3H times CBA mice. Such 'educated' cells showed strongly increased specific GVH reactivity. Lymphocytes from CBA mice previously injected with C3H times CBA cells showed reduced capacity to proliferate when injected into irradiated C3H times CBA hybrids and a poor capacity to develop new 'effector' cells reactive against C3H times CBA bone marrow target cells. The results indicate that the presence of specifically 'MLC-responsive' lymphocytes in a lymphoid cell population is a prerequisite  of its production of 'effector' cells able to respond in this GVH assay."}
{"id": "PMID:241117", "title": "Immunoelectroosmophoresis (IEOP) for detection of bacterial antigens in cerebrospinal fluid.", "content": "365 cerebrospinal fluid specimens from 259 patients were tested by the immunoelectroosmophoretic (IEOP) method to detect bacterial antigens. 25 patients had bacterial meningitis. The bacterial agent was identified by IEOP in 16 of 21 cases with aetiological agents detectable with the antisera employed. No false positive reactions occurred. The test gave true negative results in 340 instances. The rapidity, simplicity, sensitivity, reliability and low cost are emphasized.", "contents": "Immunoelectroosmophoresis (IEOP) for detection of bacterial antigens in cerebrospinal fluid. 365 cerebrospinal fluid specimens from 259 patients were tested by the immunoelectroosmophoretic (IEOP) method to detect bacterial antigens. 25 patients had bacterial meningitis. The bacterial agent was identified by IEOP in 16 of 21 cases with aetiological agents detectable with the antisera employed. No false positive reactions occurred. The test gave true negative results in 340 instances. The rapidity, simplicity, sensitivity, reliability and low cost are emphasized."}
{"id": "PMID:241118", "title": "Meningitis developing during cephalothin therapy of septicaemia.", "content": "A 63-year-old woman developed pneumococcal meningitis during cephalothin treatment for pneumococcal septicaemia. The poor penetration of this antibiotic over the blood-brain barrier makes it unsuitable for the therapy of meningitis. If cephalothin is used in other serious infections, the patient should be closely observed for the development of meningitis.", "contents": "Meningitis developing during cephalothin therapy of septicaemia. A 63-year-old woman developed pneumococcal meningitis during cephalothin treatment for pneumococcal septicaemia. The poor penetration of this antibiotic over the blood-brain barrier makes it unsuitable for the therapy of meningitis. If cephalothin is used in other serious infections, the patient should be closely observed for the development of meningitis."}
{"id": "PMID:241119", "title": "Erythromycin stearate in acute maxillary sinusitis.", "content": "76 patients with acute maxillary sinusitis were treated with oral erythromycin stearate (500 mg twice or 3 times a day for 10 days). The mean concentration of erythromycin in the sinus secretion after 3-5 days' treatment was 0.6 mug/ml with the lower dosage and 1.3 mug/ml with the higher. The concentration of erythromycin in the sinus secretion was, on the average, 10-20 times higher than the minimum inhibitory concentration (MIC) for group A streptococci and pneumococci, and reached MIC values for 15-30% of 100 examined strains of Haemophilus influenzae. 81% of the patients given the smaller and 94% of those given the larger dose improved or recovered. Radiological improvement was demonstrated in both groups. The infections with H. influenzae tended to respond somewhat less to the treatment than those with pneumococci. Comparisons of the roentgen findings and the findings at aspiration showed good agreement. An extra projection taken with the patient recumbent and the affected side downwards gave no information above that obtained from the routine projections. The large dose caused side effects more often (in 17/41 patients) than the smaller one (4/35 patients). In 10 patients treatment was discontinued because of side effects; 8 of them had received the larger dose.", "contents": "Erythromycin stearate in acute maxillary sinusitis. 76 patients with acute maxillary sinusitis were treated with oral erythromycin stearate (500 mg twice or 3 times a day for 10 days). The mean concentration of erythromycin in the sinus secretion after 3-5 days' treatment was 0.6 mug/ml with the lower dosage and 1.3 mug/ml with the higher. The concentration of erythromycin in the sinus secretion was, on the average, 10-20 times higher than the minimum inhibitory concentration (MIC) for group A streptococci and pneumococci, and reached MIC values for 15-30% of 100 examined strains of Haemophilus influenzae. 81% of the patients given the smaller and 94% of those given the larger dose improved or recovered. Radiological improvement was demonstrated in both groups. The infections with H. influenzae tended to respond somewhat less to the treatment than those with pneumococci. Comparisons of the roentgen findings and the findings at aspiration showed good agreement. An extra projection taken with the patient recumbent and the affected side downwards gave no information above that obtained from the routine projections. The large dose caused side effects more often (in 17/41 patients) than the smaller one (4/35 patients). In 10 patients treatment was discontinued because of side effects; 8 of them had received the larger dose."}
{"id": "PMID:241121", "title": "Neurotransmitters increase cyclic nucleotides in postganglionic neurons: immunocytochemical demonstration.", "content": "Dopamine increases adenosine 3',5'-monophosphate (cyclic AMP) but not guanosine 3',5'-monophosphate (cyclic GMP) in slices of bovine sympathetic ganglion; this increase is localized to the postganglionic neurons. Conversely, acetylcholine increases cyclic GMP but not cycle AMP in the ganglion; this increase also occurs within postganglionic neurons. Thus, different neurotransmitters can selectively alter cyclic nucleotide levels within the same neuronal population.", "contents": "Neurotransmitters increase cyclic nucleotides in postganglionic neurons: immunocytochemical demonstration. Dopamine increases adenosine 3',5'-monophosphate (cyclic AMP) but not guanosine 3',5'-monophosphate (cyclic GMP) in slices of bovine sympathetic ganglion; this increase is localized to the postganglionic neurons. Conversely, acetylcholine increases cyclic GMP but not cycle AMP in the ganglion; this increase also occurs within postganglionic neurons. Thus, different neurotransmitters can selectively alter cyclic nucleotide levels within the same neuronal population."}
{"id": "PMID:241124", "title": "Effect of anesthetics on the heart.", "content": "In man, high doses of the \"group 1\" inhalation anesthetics (diethylether, cyclopropane, and fluroxene) produce relatively minor depression of ventricular function, although it is possible to depress the heart if the dose is great enough. The \"group 2\" drugs (halothane, methoxyflurane, etc.) produce dose-related depression in cardiac function, but reasonable caridac outputs and blood pressure can be maintained at light anethetic levels. Much the same can also be said for the intravenous barbiturates and other hypnotics. If ventilation is supported and hypovolemia avoided, large doses of the narcotic analgesics appear to produce minimal cardiac effects. The only intravenous drug which stimulates the heart is the dissociative anesthetic ketamine, and this is probably an autonomic, reflex phenomenon (as with group 1 inhalation anesthetics). Regional anesthesia and the neuromuscular blocking drugs appear to have relatively little effect on ventricular function. Most of the work in man on the effect of anesthetics has been in healthy patients or volunteers. The effects on patients with severe heart or other systemic disease may well be different. In fact, low concentrations of fluroxene have been shown to produce significant depression of stroke volume in patients with aortic vavular disease in contrast to the effects on healthy volunteers. All potent central nervous system depressant drugs possess the potential for significant cardiac depression. If such depression is undersirable in a particular patient, the only safe way to administer anesthesia is by careful titration of the dose against the best measurement of cardiac function which is available. At the present time, this would mean measuring at least direct arterial pressure, central venous pressure, and a continuous electrocardiogram. The optimal management would prpbably include recording systolic time intervals, pulmonary capillary wedge pressure, and some measure of cardiac output as well. All the skill and pharmacologic knowledge available connot substitute for vigilant monitoring and carful tiration of drug dose in the clinical situation.", "contents": "Effect of anesthetics on the heart. In man, high doses of the \"group 1\" inhalation anesthetics (diethylether, cyclopropane, and fluroxene) produce relatively minor depression of ventricular function, although it is possible to depress the heart if the dose is great enough. The \"group 2\" drugs (halothane, methoxyflurane, etc.) produce dose-related depression in cardiac function, but reasonable caridac outputs and blood pressure can be maintained at light anethetic levels. Much the same can also be said for the intravenous barbiturates and other hypnotics. If ventilation is supported and hypovolemia avoided, large doses of the narcotic analgesics appear to produce minimal cardiac effects. The only intravenous drug which stimulates the heart is the dissociative anesthetic ketamine, and this is probably an autonomic, reflex phenomenon (as with group 1 inhalation anesthetics). Regional anesthesia and the neuromuscular blocking drugs appear to have relatively little effect on ventricular function. Most of the work in man on the effect of anesthetics has been in healthy patients or volunteers. The effects on patients with severe heart or other systemic disease may well be different. In fact, low concentrations of fluroxene have been shown to produce significant depression of stroke volume in patients with aortic vavular disease in contrast to the effects on healthy volunteers. All potent central nervous system depressant drugs possess the potential for significant cardiac depression. If such depression is undersirable in a particular patient, the only safe way to administer anesthesia is by careful titration of the dose against the best measurement of cardiac function which is available. At the present time, this would mean measuring at least direct arterial pressure, central venous pressure, and a continuous electrocardiogram. The optimal management would prpbably include recording systolic time intervals, pulmonary capillary wedge pressure, and some measure of cardiac output as well. All the skill and pharmacologic knowledge available connot substitute for vigilant monitoring and carful tiration of drug dose in the clinical situation."}
{"id": "PMID:241130", "title": "[Occurrence, diagnosis and course of chronic hepatitis in weaned lambs of a flock of Texel sheep (author's transl)].", "content": "A disease of weaned lambs is described, which is attributable to chronic hepatitis marked by impaired secretion of cholephils in the acute or early stage and by inadequate growth due to persistent dysfunction of the liver during the subsequent or chronic stage. Regardless of its duration, the disease may be diagnosed in the living animal by determining the SDH and gammaGT activity levels, the total serum protein, the serum iron concentration and the serum iron-binding capacity.", "contents": "[Occurrence, diagnosis and course of chronic hepatitis in weaned lambs of a flock of Texel sheep (author's transl)]. A disease of weaned lambs is described, which is attributable to chronic hepatitis marked by impaired secretion of cholephils in the acute or early stage and by inadequate growth due to persistent dysfunction of the liver during the subsequent or chronic stage. Regardless of its duration, the disease may be diagnosed in the living animal by determining the SDH and gammaGT activity levels, the total serum protein, the serum iron concentration and the serum iron-binding capacity."}
{"id": "PMID:241131", "title": "[The use of analgesic and antiphlogistic agents in small animals (author's transl)].", "content": "The metabolism of many analgesic and antiphlogistic agents in dogs and cats differs markedly from that in man or other animals. When the known data on the subject are borne in mind, potentially toxic agents such as acetosal, phenylbutazone, ibuprofen and indomethacin may be used without much risk in various indications. It is pointed out that double-blind studies on the clincal effectiveness in patients unfortunately have not yet become available.", "contents": "[The use of analgesic and antiphlogistic agents in small animals (author's transl)]. The metabolism of many analgesic and antiphlogistic agents in dogs and cats differs markedly from that in man or other animals. When the known data on the subject are borne in mind, potentially toxic agents such as acetosal, phenylbutazone, ibuprofen and indomethacin may be used without much risk in various indications. It is pointed out that double-blind studies on the clincal effectiveness in patients unfortunately have not yet become available."}
{"id": "PMID:241136", "title": "Hydro-proteolytic activity in rat's pancreas after irradiation.", "content": "Investigations were carried out on the problem of hydrolytic ability of rat's pancreas 24 h after whole body irradiation with the single dose of 800 R and after fractionated irradiation (5 x 150 R). Besides kallikrein, enzymes of intracellular digestion (B-glucuronidase, acid phosphatase, cathepsin) and enzymes of intraluminal digestion (amylase, lipase) were chosed for examination. It was stated, that single irradiation evokes rather moderate changes in the activity of examined enzymes causing increase of catheptic and lipolytic activity and decrease in amylase activity accompanied by sharp increase of kallikrein activity in the tissue. Mechanical obstruction of biliopancreatic duct renders trend to decrease of enzymatic activity in almost all enzymes of irradiated group. After fractionated irradiation the general increase of hydroproteolytic activity (with one exception of pancreatic amylase) was stated.", "contents": "Hydro-proteolytic activity in rat's pancreas after irradiation. Investigations were carried out on the problem of hydrolytic ability of rat's pancreas 24 h after whole body irradiation with the single dose of 800 R and after fractionated irradiation (5 x 150 R). Besides kallikrein, enzymes of intracellular digestion (B-glucuronidase, acid phosphatase, cathepsin) and enzymes of intraluminal digestion (amylase, lipase) were chosed for examination. It was stated, that single irradiation evokes rather moderate changes in the activity of examined enzymes causing increase of catheptic and lipolytic activity and decrease in amylase activity accompanied by sharp increase of kallikrein activity in the tissue. Mechanical obstruction of biliopancreatic duct renders trend to decrease of enzymatic activity in almost all enzymes of irradiated group. After fractionated irradiation the general increase of hydroproteolytic activity (with one exception of pancreatic amylase) was stated."}
{"id": "PMID:241137", "title": "Radiation effects on rat testes. IX. Studies on oxidative enzymes after partial body gamma irradiation.", "content": "Oxidative enzymes in the rat testes have been studied after gamma irradiation. The role of these enzymes in relation to spermatogenesis and steroidogenesis after radiation injury to testis has been discussed. Loss of succinic dehydrogenase and sorbitol dehydrogenase reflects the losts of germ cell population. Malic enzyme and malic dehydrogenase seem to the related to the deficiency of steroid hormones, whereas increase in glucose-6-phosphate dehydrogenase and NADP isocitric dehydrogenase is due to secondary stimulation of pituitary.", "contents": "Radiation effects on rat testes. IX. Studies on oxidative enzymes after partial body gamma irradiation. Oxidative enzymes in the rat testes have been studied after gamma irradiation. The role of these enzymes in relation to spermatogenesis and steroidogenesis after radiation injury to testis has been discussed. Loss of succinic dehydrogenase and sorbitol dehydrogenase reflects the losts of germ cell population. Malic enzyme and malic dehydrogenase seem to the related to the deficiency of steroid hormones, whereas increase in glucose-6-phosphate dehydrogenase and NADP isocitric dehydrogenase is due to secondary stimulation of pituitary."}
{"id": "PMID:241138", "title": "24xi-Methylcholestane-3beta, 5alpha, 6beta, 12beta, 25-pentol 25-monoacetate, a novel polyoxygenated marine sterol.", "content": "24xi--Methylcholestane-3beta, 5alpha, 6beta, 12beta, 25-pentol 25-monoacetate has been isolated from an Alyconarian and its structure was established in part through extensive high resolution mass spectral and nmr studies and partly through the nonidentity of one of its degradation products with 24xi-methylcholestane-3beta, 5alpha, 6beta, 12alpha-tetrol synthesized from deoxycholic acid.", "contents": "24xi-Methylcholestane-3beta, 5alpha, 6beta, 12beta, 25-pentol 25-monoacetate, a novel polyoxygenated marine sterol. 24xi--Methylcholestane-3beta, 5alpha, 6beta, 12beta, 25-pentol 25-monoacetate has been isolated from an Alyconarian and its structure was established in part through extensive high resolution mass spectral and nmr studies and partly through the nonidentity of one of its degradation products with 24xi-methylcholestane-3beta, 5alpha, 6beta, 12alpha-tetrol synthesized from deoxycholic acid."}
{"id": "PMID:241143", "title": "Bone marrow transplantation in the busulfan-treated rat. I. Effect of cyclophosphamide and rabbit antirat thymocyte serum as immunosuppression.", "content": "It was previously shown that lethal doses of busulfan (BU) were not immunosuppressive in the rat. In the present studies the effect of rabbit antirat thymocyte serum (RARTS) and cyclophosphamide (CY) as immunosuppressive preparation for marrow allografts in the rat given supralethal doses of BU was investigated. Lewis or LBNF rats were given RARTS for 4-12 consecutive daily doses. They were given a supralethal dose of BU in addition on the last day of RARTS administration. Ag-B-incompatible (ACI). Ag-B-compatible (F344), or syngeneic marrow was infused 24 hr later. In general, RARTS was not toxic to the marrow graft and permitted engraftment of Ag-B-incompatible and compatible marrow. All animals given Ag-B-incompatible marrow and Ag-B-compatible marrow that survived to day 21 were shown to be chimeric, but all those with incompatible marrow subsequently died from severe graft-versus-host disease (GVHD). In other experiments Lewis or LBNF1 rats were given Ag-B-incompatible (ACI) and compatible (F344) marrow after a supralethal dose of BU and single graded doses of CY. Doses of CY as low as 25-50 mg/kg provided sufficient immunosuppression to allow allogeneic engraftment. Transient chimerism was seen up to doses of 100 mg/kg of CY. Permanent chimerism was seen with doses of CY from 150 to 250 mg/kg. The incidence of lethal GVHD increased in parallel with the percentage of animals that were demonstrated to be chimeric. Mild but transient GVHD was seen with Ag-B-compatible marrow given to Lewis rats.", "contents": "Bone marrow transplantation in the busulfan-treated rat. I. Effect of cyclophosphamide and rabbit antirat thymocyte serum as immunosuppression. It was previously shown that lethal doses of busulfan (BU) were not immunosuppressive in the rat. In the present studies the effect of rabbit antirat thymocyte serum (RARTS) and cyclophosphamide (CY) as immunosuppressive preparation for marrow allografts in the rat given supralethal doses of BU was investigated. Lewis or LBNF rats were given RARTS for 4-12 consecutive daily doses. They were given a supralethal dose of BU in addition on the last day of RARTS administration. Ag-B-incompatible (ACI). Ag-B-compatible (F344), or syngeneic marrow was infused 24 hr later. In general, RARTS was not toxic to the marrow graft and permitted engraftment of Ag-B-incompatible and compatible marrow. All animals given Ag-B-incompatible marrow and Ag-B-compatible marrow that survived to day 21 were shown to be chimeric, but all those with incompatible marrow subsequently died from severe graft-versus-host disease (GVHD). In other experiments Lewis or LBNF1 rats were given Ag-B-incompatible (ACI) and compatible (F344) marrow after a supralethal dose of BU and single graded doses of CY. Doses of CY as low as 25-50 mg/kg provided sufficient immunosuppression to allow allogeneic engraftment. Transient chimerism was seen up to doses of 100 mg/kg of CY. Permanent chimerism was seen with doses of CY from 150 to 250 mg/kg. The incidence of lethal GVHD increased in parallel with the percentage of animals that were demonstrated to be chimeric. Mild but transient GVHD was seen with Ag-B-compatible marrow given to Lewis rats."}
{"id": "PMID:241144", "title": "Chimaerism of immunocompetent cells in allogeneic bone marrow-reconstituted lethally irradiated chickens.", "content": "Injection of parental bone marrow cells into 12-day-old lethally irradiated F1 hybrid chickens resulted in chimaerism of donor-type graft-versus-host (GVH)-reactive cells and suppression of antisheep red blood cell antibody response. These manifestations of a chronic graft-versus-host reaction were prevented by pretreatment of the donor marrow with specific anti-T cell globulin. In some chimaeras donor-type GVH-reactive cells developed gradually from T cells precursors of donor origin. Transplantation of spleen and marrow cells from sheep red blood cell-primed F1 hybrid donors into lethally irradiated parental recipients resulted in the loss of memory potential within 1-2 weeks of transfer, whereas donor-type IgG allotype synthesis was preserved. Injection of goat antichicken thymocyte serum to recipients 1 day before reconstitution enabled the antibody response of memory cells at 1-2 weeks, although it failed to prevent their rejection by 8-9 weeeks after transplantation. Split chimaerism of donor-type GVH-reactive cells was demonstrated in chickens which had previously rejected the B cells derived from the same graft.", "contents": "Chimaerism of immunocompetent cells in allogeneic bone marrow-reconstituted lethally irradiated chickens. Injection of parental bone marrow cells into 12-day-old lethally irradiated F1 hybrid chickens resulted in chimaerism of donor-type graft-versus-host (GVH)-reactive cells and suppression of antisheep red blood cell antibody response. These manifestations of a chronic graft-versus-host reaction were prevented by pretreatment of the donor marrow with specific anti-T cell globulin. In some chimaeras donor-type GVH-reactive cells developed gradually from T cells precursors of donor origin. Transplantation of spleen and marrow cells from sheep red blood cell-primed F1 hybrid donors into lethally irradiated parental recipients resulted in the loss of memory potential within 1-2 weeks of transfer, whereas donor-type IgG allotype synthesis was preserved. Injection of goat antichicken thymocyte serum to recipients 1 day before reconstitution enabled the antibody response of memory cells at 1-2 weeks, although it failed to prevent their rejection by 8-9 weeeks after transplantation. Split chimaerism of donor-type GVH-reactive cells was demonstrated in chickens which had previously rejected the B cells derived from the same graft."}
{"id": "PMID:241145", "title": "Some aspects of HB Ag in hepatitis in Sri Lanka.", "content": "Twenty-four out of 72 sera from patients with acute viral hepatitis were positive for HB Ag. HB Ag positive males were more severely ill than HB Ag positive females. The sera of four patients with active chronic hepatitis were negative for HB Ag. Thirteen sera of HB Ag positive cases were tested for anti-nuclear factor, all with negative results. In all four patients with active chronic hepatitis anti-nuclear factor was positive. There was a high incidence of latex fixation reactivity in the HB Ag positive cases (9 out of 13). Arbovirus antibodies were detected in 16 out of 18 HB Ag positive cases and in 19 out of 27 HB Ag negative cases of acture viral hepatitis. Fifty percent of these HB Ag positive cases had titers suggestive of recent infection as against 33% of the HB Ag negative cases. The arbovirus antibody titers were determined in four out of six HB Ag positive cases that did not give a history of parenteral injections and in everyone of them the titers were suggestive of a recent arbovirus infection.", "contents": "Some aspects of HB Ag in hepatitis in Sri Lanka. Twenty-four out of 72 sera from patients with acute viral hepatitis were positive for HB Ag. HB Ag positive males were more severely ill than HB Ag positive females. The sera of four patients with active chronic hepatitis were negative for HB Ag. Thirteen sera of HB Ag positive cases were tested for anti-nuclear factor, all with negative results. In all four patients with active chronic hepatitis anti-nuclear factor was positive. There was a high incidence of latex fixation reactivity in the HB Ag positive cases (9 out of 13). Arbovirus antibodies were detected in 16 out of 18 HB Ag positive cases and in 19 out of 27 HB Ag negative cases of acture viral hepatitis. Fifty percent of these HB Ag positive cases had titers suggestive of recent infection as against 33% of the HB Ag negative cases. The arbovirus antibody titers were determined in four out of six HB Ag positive cases that did not give a history of parenteral injections and in everyone of them the titers were suggestive of a recent arbovirus infection."}
{"id": "PMID:241146", "title": "[Study of the mutagenic activity of mazheptil].", "content": "Mutagenic activity of the psychotropid drug--majeptil was studied. Majeptil does not induce gene mutations on Salmonella typhimurium and chromosomal aberrations in mice bone marrow cells in vivo. It is shown that majeptil increase the level of chromosome aberrations in the culture of human peripheral blood lymphocytes. It is also active in the dominant lethal test on mice.", "contents": "[Study of the mutagenic activity of mazheptil]. Mutagenic activity of the psychotropid drug--majeptil was studied. Majeptil does not induce gene mutations on Salmonella typhimurium and chromosomal aberrations in mice bone marrow cells in vivo. It is shown that majeptil increase the level of chromosome aberrations in the culture of human peripheral blood lymphocytes. It is also active in the dominant lethal test on mice."}
{"id": "PMID:241154", "title": "Measurement of substrate-induced oxygen uptake during microsomal drug oxidation using a gold micro-electrode.", "content": "1. A resin-coated gold micro-electrode has been used for polarographic determination of oxygen concentration in liver microsomal suspensions from phenobarbital-pretreated rats. 2. The rate of oxygen uptake on addition of an NADPH-regenerating system and the rate after addition of various substrates of the mixed function oxidase system were measured. The rate of oxygen uptake was faster in the presence of substrate than in the presence of NADPH alone. 3. Kinetic constants (Km and V max) for biphenyl, hexobarbital, ethylmorphine, naphthalene and SKF 525-A measured by this technique compare favourably with those obtained either by measurements of NADPH oxidation, or chemical measurements of substrate disappearance or product formation. 4. The practical applications of the gold electrode to drug metabolism studies are discussed.", "contents": "Measurement of substrate-induced oxygen uptake during microsomal drug oxidation using a gold micro-electrode. 1. A resin-coated gold micro-electrode has been used for polarographic determination of oxygen concentration in liver microsomal suspensions from phenobarbital-pretreated rats. 2. The rate of oxygen uptake on addition of an NADPH-regenerating system and the rate after addition of various substrates of the mixed function oxidase system were measured. The rate of oxygen uptake was faster in the presence of substrate than in the presence of NADPH alone. 3. Kinetic constants (Km and V max) for biphenyl, hexobarbital, ethylmorphine, naphthalene and SKF 525-A measured by this technique compare favourably with those obtained either by measurements of NADPH oxidation, or chemical measurements of substrate disappearance or product formation. 4. The practical applications of the gold electrode to drug metabolism studies are discussed."}
{"id": "PMID:241155", "title": "The metabolism of N-ethyl-N-methylaniline by rabbit liver microsomes: the measurement of metabolites by gas-liquid chromatography.", "content": "1. A method for the determination of N-ethyl-N-methylaniline and its metabolites by g.l.c. is described. 2. Following incubation in N-ethyl-N-methylaniline with rabbit liver microsomes for 60 min, over 95% of the substrate was accounted for as unchanged compound or metabolites. 3. N-Ethyl-N-methylaniline is metabolized in vitro by rabbit tissues mainly by N-oxidation and N-demethylation and to a lesser extent by N-deethylation and di-dealkylation. 4. Both major routes of metabolism were observed in homogenates prepared from rabbit liver and lung; in addition N-oxidation occurred in kidney and bladder tissue homogenates.", "contents": "The metabolism of N-ethyl-N-methylaniline by rabbit liver microsomes: the measurement of metabolites by gas-liquid chromatography. 1. A method for the determination of N-ethyl-N-methylaniline and its metabolites by g.l.c. is described. 2. Following incubation in N-ethyl-N-methylaniline with rabbit liver microsomes for 60 min, over 95% of the substrate was accounted for as unchanged compound or metabolites. 3. N-Ethyl-N-methylaniline is metabolized in vitro by rabbit tissues mainly by N-oxidation and N-demethylation and to a lesser extent by N-deethylation and di-dealkylation. 4. Both major routes of metabolism were observed in homogenates prepared from rabbit liver and lung; in addition N-oxidation occurred in kidney and bladder tissue homogenates."}
{"id": "PMID:241156", "title": "The differentiation of N-oxidation and N-dealkylation of N-ethyl-N-methylaniline by rabbit liver microsomes as distinct metabolic routes.", "content": "1. N-Oxidation and N-dealkylation were shown to be separate routes of metabolism for N-ethyl-N-methylaniline. 2. N-Dealkylation, but not N-oxidation, is enhanced when NADH is present in addition to the NADPH-regenerating cofactors. 3. Some inhibitors, e.g. p-chloromercuribenzoate, inhibit N-dealkylation to a very much greater extent than they do N-oxidation. 4. N-Dealkylation is affected more by 'ageing' of the microsomal preparation or by the presence of bile salts, than is N-oxidation. 5. N-Oxidation followed by N-O-alpha-carbon migration of oxygen is only implicated to a very minor extent in the N-dealkylation process.", "contents": "The differentiation of N-oxidation and N-dealkylation of N-ethyl-N-methylaniline by rabbit liver microsomes as distinct metabolic routes. 1. N-Oxidation and N-dealkylation were shown to be separate routes of metabolism for N-ethyl-N-methylaniline. 2. N-Dealkylation, but not N-oxidation, is enhanced when NADH is present in addition to the NADPH-regenerating cofactors. 3. Some inhibitors, e.g. p-chloromercuribenzoate, inhibit N-dealkylation to a very much greater extent than they do N-oxidation. 4. N-Dealkylation is affected more by 'ageing' of the microsomal preparation or by the presence of bile salts, than is N-oxidation. 5. N-Oxidation followed by N-O-alpha-carbon migration of oxygen is only implicated to a very minor extent in the N-dealkylation process."}
{"id": "PMID:241157", "title": "Enzymic N-acetylation of 2,4-toluenediamine by liver cytosols from various species.", "content": "1. 2,4-Toluenediamine was incubated with liver cytosol from various species, or cytosol from various tissues of the hamster or rabbit, in the presence of [1-14C]acetyl-CoA. N-Acetylation occurred selectively at the p-amino group of 2,4-toluenediamine and to a much lesser extent on the o-amino group. 2. In hamsters and rabbits the highest N-acetyltransferase activity was present in the liver cytosol, followed by kidney intestinal mucosa and lung cytosols. 3. Hamster liver cytosol had the greatest activity followed by liver cytosols from guinea-pig, rabbit, mouse and rat. With human liver cytosol only a trace of an N-acetyl derivative of 2,4-toluenediamine was found while dog liver cytosol showed no activity. 4. N-Acetyltransferase activity was maximal at pH 7-5 in mouse, pH 6-0 in rat and man, and pH 7-0 in rabbit liver cytosols. 5. There was a slight difference in the levels of N-acetyltransferases in males and females; the female mouse had more enzyme activity than the male, but the male rat had more enzyme activity than the female.", "contents": "Enzymic N-acetylation of 2,4-toluenediamine by liver cytosols from various species. 1. 2,4-Toluenediamine was incubated with liver cytosol from various species, or cytosol from various tissues of the hamster or rabbit, in the presence of [1-14C]acetyl-CoA. N-Acetylation occurred selectively at the p-amino group of 2,4-toluenediamine and to a much lesser extent on the o-amino group. 2. In hamsters and rabbits the highest N-acetyltransferase activity was present in the liver cytosol, followed by kidney intestinal mucosa and lung cytosols. 3. Hamster liver cytosol had the greatest activity followed by liver cytosols from guinea-pig, rabbit, mouse and rat. With human liver cytosol only a trace of an N-acetyl derivative of 2,4-toluenediamine was found while dog liver cytosol showed no activity. 4. N-Acetyltransferase activity was maximal at pH 7-5 in mouse, pH 6-0 in rat and man, and pH 7-0 in rabbit liver cytosols. 5. There was a slight difference in the levels of N-acetyltransferases in males and females; the female mouse had more enzyme activity than the male, but the male rat had more enzyme activity than the female."}
{"id": "PMID:241158", "title": "Properties of benzpyrene hydroxylase from human liver and comparison with the rat, rabbit and guinea-pig enzymes.", "content": "1. Benzpyrene hydroxylase of human liver biopsies and of livers from four inbred rat strains and from a non-inbred Sprague-Dawley rat strain, rabbit and guinea-pig was studied. 2. The human liver benzpyrene hydroxylase was similar to that of laboratory animals with respect to cofactor requirements, NADPH and O2, microsomal localization and inhibition by CO and N2. 3. Kinetic analysis of human adult benzpyrene hydroxylase indicated the presence of two enzymes, whereas human foetal liver contained only one enzyme hydroxylating 3,4-benzpyrene. Michaelis constants of human liver benzpyrene hydroxylase were slightly higher than Km values of animal liver enzymes. 4. Benzpyrene hydroxylase activity in human liver showed no sex difference, was enhanced by cigarette smoking and was decreased in patients with liver damage. 5. Variation of benzpyrene hydroxylase activity in human liver samples was about 6-fold in the 'control' group and 16-fold when all patients were considered. Variation of benzpyrene hydroxylase activity in inbred rat strains was less than 60% between different individuals and in the non-inbred rat, rabbit and guinea-pig the variation was 2- to 3-fold or less.", "contents": "Properties of benzpyrene hydroxylase from human liver and comparison with the rat, rabbit and guinea-pig enzymes. 1. Benzpyrene hydroxylase of human liver biopsies and of livers from four inbred rat strains and from a non-inbred Sprague-Dawley rat strain, rabbit and guinea-pig was studied. 2. The human liver benzpyrene hydroxylase was similar to that of laboratory animals with respect to cofactor requirements, NADPH and O2, microsomal localization and inhibition by CO and N2. 3. Kinetic analysis of human adult benzpyrene hydroxylase indicated the presence of two enzymes, whereas human foetal liver contained only one enzyme hydroxylating 3,4-benzpyrene. Michaelis constants of human liver benzpyrene hydroxylase were slightly higher than Km values of animal liver enzymes. 4. Benzpyrene hydroxylase activity in human liver showed no sex difference, was enhanced by cigarette smoking and was decreased in patients with liver damage. 5. Variation of benzpyrene hydroxylase activity in human liver samples was about 6-fold in the 'control' group and 16-fold when all patients were considered. Variation of benzpyrene hydroxylase activity in inbred rat strains was less than 60% between different individuals and in the non-inbred rat, rabbit and guinea-pig the variation was 2- to 3-fold or less."}
{"id": "PMID:241159", "title": "[Precursor formation and biosynthesis of the macrolide antibiotic a 6599 (turimycin) by streptomyces hygroscopicus JA 6599].", "content": "The possible role of some metabolic systems producing acetyl-CoA, and methylmalonyl-CoA as initial precursors in the biosynthesis of the macrolide antibiotic A 6599 by Streptomyces hygroscopicus JA 6599 was studied. The activities of pyruvate decarboxylase exceeded in two higher producing strains about twofold those found in the mycelium of a lower producing one suggesting that in this organism an enhanced production of acetyl-CoA should be one of the prerequisites necessary for an improved antibiotic biosynthesis. No clear interrelationship was established, however, between the biosynthesis of the secondary metabolite A 6599 on the one hand and the acetate and propionate kinase content on the other hand. In S. hygroscopicus JA 6599 the carboxylation of acetyl-CoA or propionyl-CoA seems to be the major pathway giving malonyl-CoA or methylmalonyl-CoA, respectively. Thus, the activities of acetyl-CoA and propionyl-CoA carboxylases corresponded with both the levels of antibiotic production in several strains and with variations observed in the specific antibiotic production rate during the cultivation. Some other pathways synthesizing these precursors, e.g. via oxaloacetate, are assumed to be negligible since even in the mycelium of the lower producing strain increased activities of phosphoenolpyruvate carboxylase were present.", "contents": "[Precursor formation and biosynthesis of the macrolide antibiotic a 6599 (turimycin) by streptomyces hygroscopicus JA 6599]. The possible role of some metabolic systems producing acetyl-CoA, and methylmalonyl-CoA as initial precursors in the biosynthesis of the macrolide antibiotic A 6599 by Streptomyces hygroscopicus JA 6599 was studied. The activities of pyruvate decarboxylase exceeded in two higher producing strains about twofold those found in the mycelium of a lower producing one suggesting that in this organism an enhanced production of acetyl-CoA should be one of the prerequisites necessary for an improved antibiotic biosynthesis. No clear interrelationship was established, however, between the biosynthesis of the secondary metabolite A 6599 on the one hand and the acetate and propionate kinase content on the other hand. In S. hygroscopicus JA 6599 the carboxylation of acetyl-CoA or propionyl-CoA seems to be the major pathway giving malonyl-CoA or methylmalonyl-CoA, respectively. Thus, the activities of acetyl-CoA and propionyl-CoA carboxylases corresponded with both the levels of antibiotic production in several strains and with variations observed in the specific antibiotic production rate during the cultivation. Some other pathways synthesizing these precursors, e.g. via oxaloacetate, are assumed to be negligible since even in the mycelium of the lower producing strain increased activities of phosphoenolpyruvate carboxylase were present."}
{"id": "PMID:241163", "title": "[Perinatal mortality and asphyxia in premature babies (author's transl)].", "content": "The aim of the present investigation was to study the influence of O2-ventilation, blind buffer therapy with Na-bicarbonate, late cord clamping and infusion of low molculare weight dextran on morbidity of Respiratory-Distress-Syndrom (RDS) and mortality during the first week in infants with a birthweight of 2500 g and less. The charts of 536 infants were studied. There were 481 life birth and 55 stillbirth (10.2%). In 185 infants the pH and Base-excess in the umbilical arterial blood was meassured. The infants born in 1969--1971 were compaired with them born in 1972--1973. In 52% of the \"premature infants\" the pH was 7.25 U and lower and in 90% of the Base-Excess was --4.5 meq/l and more. The perinatal mortality (PM) was 30% and 13% (P less than 0.01) resp. There was a correlation to the birthweight. The decrease of the PM was related to the fall in mortality of infant during the first week: 21% and 4% resp. Here too, there was a correlation to birthweight and gestational age. The morbidity in RDS: 20.6% and 10.0% (P less than 0.01) and mortality following RDS: 79.3% and 35.0% resp. (P less than 0.01) was also low in 1972--1973. The results permit us to conclude that it is of great importance to correct fetal acidosis immediately after birth to prevent irreversible alterations in the lung. It could also be of value to encrease cardiac output and lungperfusion by late cord clamping and injection of dextran 40. The other procedures belong to standard managment in handling an asphyxiated fetus.", "contents": "[Perinatal mortality and asphyxia in premature babies (author's transl)]. The aim of the present investigation was to study the influence of O2-ventilation, blind buffer therapy with Na-bicarbonate, late cord clamping and infusion of low molculare weight dextran on morbidity of Respiratory-Distress-Syndrom (RDS) and mortality during the first week in infants with a birthweight of 2500 g and less. The charts of 536 infants were studied. There were 481 life birth and 55 stillbirth (10.2%). In 185 infants the pH and Base-excess in the umbilical arterial blood was meassured. The infants born in 1969--1971 were compaired with them born in 1972--1973. In 52% of the \"premature infants\" the pH was 7.25 U and lower and in 90% of the Base-Excess was --4.5 meq/l and more. The perinatal mortality (PM) was 30% and 13% (P less than 0.01) resp. There was a correlation to the birthweight. The decrease of the PM was related to the fall in mortality of infant during the first week: 21% and 4% resp. Here too, there was a correlation to birthweight and gestational age. The morbidity in RDS: 20.6% and 10.0% (P less than 0.01) and mortality following RDS: 79.3% and 35.0% resp. (P less than 0.01) was also low in 1972--1973. The results permit us to conclude that it is of great importance to correct fetal acidosis immediately after birth to prevent irreversible alterations in the lung. It could also be of value to encrease cardiac output and lungperfusion by late cord clamping and injection of dextran 40. The other procedures belong to standard managment in handling an asphyxiated fetus."}
{"id": "PMID:241164", "title": "[The acidity and peptic activity of gastric juice in healthy children and in children suffering from cystic fibrosis (author's transl)].", "content": "The acid concentration and quantity, the pH and the peptic activity of the gastric juice were measured after stimulation with pentagastrin in 10 children with cystic fibrosis between the ages 2 and 12 years and in 20 healthy children of the same age group. Furthermore, the basal, maximal and peak volume outputs (BVO, MVO and PVO), the basal, maximal and peak acid outputs (BAO, MAO and PAO) and the basal, maximal and peak pepsin output (BPO, MPO and PPO) were determined. The statistical calculations were carried out with the help of partial hierarchical analysis of variance, comparison of regression curves, simple analysis of covariance and the t test. After stimulation with pentagastrin, the volume of the gastric juice, the acid quantity and the peptic activity were found to be dependent on age in healthy children as well as in children with cystic fibrosis. The maximal volume of secretion in children with cystic fibrosis is less than that of healthy children; however, the acid quantity and peptic activity show no significant difference in both groups. The volume of the gastric juice, acid quantity and peptic activity in basal and stimulated secretions, expressed in kilograms per body weight or surface area in square meters, are independent of age and show no significant difference between the two groups. In the two groups the curves for the three parameters differ significantly from one to another. There is a significant shift in the time course of the curves that depict the acid secretion and peptic activity. Contrary to the accepted views, the acid and enzyme secretions are not closely interrelated. Based on the acidity and peptic activity, the digestive capacity of the stomach is the same for healthy children and children with cystic fibrosis. In contrast to the pancreas, there is no impairment in the exocrine function of the stomach. The gastric secretions of children with cystic fibrosis are not completely the same as in healthy children.", "contents": "[The acidity and peptic activity of gastric juice in healthy children and in children suffering from cystic fibrosis (author's transl)]. The acid concentration and quantity, the pH and the peptic activity of the gastric juice were measured after stimulation with pentagastrin in 10 children with cystic fibrosis between the ages 2 and 12 years and in 20 healthy children of the same age group. Furthermore, the basal, maximal and peak volume outputs (BVO, MVO and PVO), the basal, maximal and peak acid outputs (BAO, MAO and PAO) and the basal, maximal and peak pepsin output (BPO, MPO and PPO) were determined. The statistical calculations were carried out with the help of partial hierarchical analysis of variance, comparison of regression curves, simple analysis of covariance and the t test. After stimulation with pentagastrin, the volume of the gastric juice, the acid quantity and the peptic activity were found to be dependent on age in healthy children as well as in children with cystic fibrosis. The maximal volume of secretion in children with cystic fibrosis is less than that of healthy children; however, the acid quantity and peptic activity show no significant difference in both groups. The volume of the gastric juice, acid quantity and peptic activity in basal and stimulated secretions, expressed in kilograms per body weight or surface area in square meters, are independent of age and show no significant difference between the two groups. In the two groups the curves for the three parameters differ significantly from one to another. There is a significant shift in the time course of the curves that depict the acid secretion and peptic activity. Contrary to the accepted views, the acid and enzyme secretions are not closely interrelated. Based on the acidity and peptic activity, the digestive capacity of the stomach is the same for healthy children and children with cystic fibrosis. In contrast to the pancreas, there is no impairment in the exocrine function of the stomach. The gastric secretions of children with cystic fibrosis are not completely the same as in healthy children."}
{"id": "PMID:241165", "title": "Studies on the specificities of various anti-H reagents.", "content": "Four different eel serum samples and the lectins Cytisus sessilifolius and Evonymus europaeus were examined for their capacities to react with a number of preparations which show O(H) blood group-like activity. Some similarities and major differences between the anti-H reagents were observed in experiments where the \"H-like\" activities of invertebrate extracts and blood group substances were compared. A comparison of the reactivities of eel sera, catfish anti-H sera and 4 anti-H lectins with a number of different \"H-like\" preparations is summarized. Data obtained from preliminary sugar analyses of preparations isolated from 5 different invertebrate species studied is presented.", "contents": "Studies on the specificities of various anti-H reagents. Four different eel serum samples and the lectins Cytisus sessilifolius and Evonymus europaeus were examined for their capacities to react with a number of preparations which show O(H) blood group-like activity. Some similarities and major differences between the anti-H reagents were observed in experiments where the \"H-like\" activities of invertebrate extracts and blood group substances were compared. A comparison of the reactivities of eel sera, catfish anti-H sera and 4 anti-H lectins with a number of different \"H-like\" preparations is summarized. Data obtained from preliminary sugar analyses of preparations isolated from 5 different invertebrate species studied is presented."}
{"id": "PMID:241166", "title": "The immunochemistry of (L-Ala-D-Glu-L-Lys-D-Ala-Gly)n: II. Rabbit antibodies of restricted heterogeneity.", "content": "A rabbit antiserum of restricted specificity elicited by the sequential polypeptide, (L-Ala-D-Glu-L-Lys-D-Ala-Gly)n, was purified by column chromatography using Sepharose 4B to which the inhibitor, Gly-L-Ala-D-Glu-Gly, was covalently attached. Approximately 95% of the antibody activity was retained on the immunoabsorbant. After elution, the purified antibody was shown by electrofocusing in a sucrose gradient to be of restricted heterogeneity. The entire antibody fraction was contained within the pH range of 6.9-8.9. The normal immunoglobulin pool from this rabbit, on the other hand, was found by electrofocusing to be distributed throughout the pH range studied (3.6-9.2).", "contents": "The immunochemistry of (L-Ala-D-Glu-L-Lys-D-Ala-Gly)n: II. Rabbit antibodies of restricted heterogeneity. A rabbit antiserum of restricted specificity elicited by the sequential polypeptide, (L-Ala-D-Glu-L-Lys-D-Ala-Gly)n, was purified by column chromatography using Sepharose 4B to which the inhibitor, Gly-L-Ala-D-Glu-Gly, was covalently attached. Approximately 95% of the antibody activity was retained on the immunoabsorbant. After elution, the purified antibody was shown by electrofocusing in a sucrose gradient to be of restricted heterogeneity. The entire antibody fraction was contained within the pH range of 6.9-8.9. The normal immunoglobulin pool from this rabbit, on the other hand, was found by electrofocusing to be distributed throughout the pH range studied (3.6-9.2)."}
{"id": "PMID:241167", "title": "Low molecular weight water-soluble peptidoglycans as adjuvants and immunostimulants.", "content": "The tetrasaccharide-heptapeptide (TH), when injected with mineral oil, exerted a strong adjuvant effect. It stimulated B and T cells, but did not increase the phagocytic activity of the reticulo-endothelial system. While BCG exerted significant preventive effect on the growth of sarcoma 180, leucosarcomatosis an EHRLICH ascitic tumor, TH, at the doses used, was devoid of such activity.", "contents": "Low molecular weight water-soluble peptidoglycans as adjuvants and immunostimulants. The tetrasaccharide-heptapeptide (TH), when injected with mineral oil, exerted a strong adjuvant effect. It stimulated B and T cells, but did not increase the phagocytic activity of the reticulo-endothelial system. While BCG exerted significant preventive effect on the growth of sarcoma 180, leucosarcomatosis an EHRLICH ascitic tumor, TH, at the doses used, was devoid of such activity."}
{"id": "PMID:241168", "title": "[A ferredoxin-linked sulfite reductase from Spinacia oleracea (author's transl)].", "content": "A sulfite reductase from spinach has been purified 125 fold. Throughout all stages of purification the reduction of sulfite has been found dependent on ferredoxin. Reduced ferredoxin has been provided either by photosynthetic reduction in isolated, broken chloroplasts or by NADPH via the ferredoxin-NADP-oxidoreductase. During the purification procedure ferredoxin as electrondonor has been replaced by reduced methylviologen.", "contents": "[A ferredoxin-linked sulfite reductase from Spinacia oleracea (author's transl)]. A sulfite reductase from spinach has been purified 125 fold. Throughout all stages of purification the reduction of sulfite has been found dependent on ferredoxin. Reduced ferredoxin has been provided either by photosynthetic reduction in isolated, broken chloroplasts or by NADPH via the ferredoxin-NADP-oxidoreductase. During the purification procedure ferredoxin as electrondonor has been replaced by reduced methylviologen."}
{"id": "PMID:241169", "title": "[Michaelis constants of neuraminidases of pathogenic and apathogenic microorganisms (author's transl)].", "content": "The Km-values of neuraminidases from different pathogenic and apathogenic microorganisms have been determined on low and high molecular substrates. The substrate specificity and the affinity to the different types of substrates in relation to the pathogenicity of the microorganisms are discussed.", "contents": "[Michaelis constants of neuraminidases of pathogenic and apathogenic microorganisms (author's transl)]. The Km-values of neuraminidases from different pathogenic and apathogenic microorganisms have been determined on low and high molecular substrates. The substrate specificity and the affinity to the different types of substrates in relation to the pathogenicity of the microorganisms are discussed."}
{"id": "PMID:241170", "title": "Determination of the isotope effect of the enzymatic oxidation of (R)Carnitine by displacement of the equilibrium via mass action.", "content": "An isotope effect of the dehydrogenation of (R) Carnitine [(R) 3-hydroxy-4-trimethylaminobutyric acid hydrochloride] catalyzed by (R) carnitine dehydrogenase [(R) carnitine: NAD oxidoreductase E.C. 1.1.1.108] from Pseudomonas aeruginosa was measured at different temperatures. It was found that k1H/k3H does not vary greatly with changes of temperature. The value of 3 for k1H/k3H measured at small initial conversions strongly indicated that the rate limiting step of the oxidation of (R) carnitine is the cleavage of the C-H bond at C3.", "contents": "Determination of the isotope effect of the enzymatic oxidation of (R)Carnitine by displacement of the equilibrium via mass action. An isotope effect of the dehydrogenation of (R) Carnitine [(R) 3-hydroxy-4-trimethylaminobutyric acid hydrochloride] catalyzed by (R) carnitine dehydrogenase [(R) carnitine: NAD oxidoreductase E.C. 1.1.1.108] from Pseudomonas aeruginosa was measured at different temperatures. It was found that k1H/k3H does not vary greatly with changes of temperature. The value of 3 for k1H/k3H measured at small initial conversions strongly indicated that the rate limiting step of the oxidation of (R) carnitine is the cleavage of the C-H bond at C3."}
{"id": "PMID:241172", "title": "Reaction of glutathione with conjugated carbonyls.", "content": "1. GSH reacts with conjugated carbonyls according to the equation: GSH+R-CH=CH-COR in equilibrium R-CH(SG)-CH2-COR. The forward reaction follows second order, the reverse reaction first order kinetics. It is assumed that this reaction reflects best the ability of conjugated carbonyls to inactivate SH groups in biological systems. 2. The rate of forward reaction increases with pH approx. parallel with alphaSH. Besides OH- ions also proton donors (e.g. buffers) increase the rate. The catalytic effect of pH and buffer is interpreted in view of the reaction mechanism. 3. The equilibrium constants as well as the rate constants for forward (k1) and reverse reaction show an extreme variation depending on the carbonyl structure. Acrolein and methyl vinyl ketone (k1 = 120 and 32 mol-1 sec-1, resp.) react more rapidly than any other carbonyl to give very stable adducts (half-lives for reverse reaction 4.6 and 60.7 days, resp). Somewhat less reactive are 4-hydroxy-2-alkenals and 4-ketopentenoic acid (k1 between 1 and 3 mol-1 sec-1), but they also form very stable adducts showing half-lives between 3.4 and 19 days. All other carbonyl studied react either very slowly (e.g. citral, ethly crotonate, mesityl oxide, acrylic acid) or form very labile adducts (crotonal, pentenal, hexenal, 3-methyl-butenone). Comparing biological activities of conjugated carbonyls their reactivity towards HS (k1) and the stability of the adducts must be considered.", "contents": "Reaction of glutathione with conjugated carbonyls. 1. GSH reacts with conjugated carbonyls according to the equation: GSH+R-CH=CH-COR in equilibrium R-CH(SG)-CH2-COR. The forward reaction follows second order, the reverse reaction first order kinetics. It is assumed that this reaction reflects best the ability of conjugated carbonyls to inactivate SH groups in biological systems. 2. The rate of forward reaction increases with pH approx. parallel with alphaSH. Besides OH- ions also proton donors (e.g. buffers) increase the rate. The catalytic effect of pH and buffer is interpreted in view of the reaction mechanism. 3. The equilibrium constants as well as the rate constants for forward (k1) and reverse reaction show an extreme variation depending on the carbonyl structure. Acrolein and methyl vinyl ketone (k1 = 120 and 32 mol-1 sec-1, resp.) react more rapidly than any other carbonyl to give very stable adducts (half-lives for reverse reaction 4.6 and 60.7 days, resp). Somewhat less reactive are 4-hydroxy-2-alkenals and 4-ketopentenoic acid (k1 between 1 and 3 mol-1 sec-1), but they also form very stable adducts showing half-lives between 3.4 and 19 days. All other carbonyl studied react either very slowly (e.g. citral, ethly crotonate, mesityl oxide, acrylic acid) or form very labile adducts (crotonal, pentenal, hexenal, 3-methyl-butenone). Comparing biological activities of conjugated carbonyls their reactivity towards HS (k1) and the stability of the adducts must be considered."}
{"id": "PMID:241171", "title": "[Gas chromatographic mass spectrometric analysis of neurtral and acid oligosaccharides from human milk as their trimethylsilyl derivatives (author's transl)].", "content": "Gas chromatography and the 20 eV mass spectra of the human milk oligosaccharides fucosido-galactose, fucosido-lactose, di-fucosido-lactose, 3'-N-acetylneuraminyl-lactose, 6'-N-acetylneuraminyl-lactose and of N-acetyllactosamine as pertrimethylsilyl (TMS) ethers are described. The gas chromatographic separation of the L-fucose containing oligosaccharides was performed on Silicone SE 30. The sialic acid containing sugars were separated on DEXSIL 300. The correlations between oligosaccharide structures and mass spectrometric fragmentation patterns are discussed.", "contents": "[Gas chromatographic mass spectrometric analysis of neurtral and acid oligosaccharides from human milk as their trimethylsilyl derivatives (author's transl)]. Gas chromatography and the 20 eV mass spectra of the human milk oligosaccharides fucosido-galactose, fucosido-lactose, di-fucosido-lactose, 3'-N-acetylneuraminyl-lactose, 6'-N-acetylneuraminyl-lactose and of N-acetyllactosamine as pertrimethylsilyl (TMS) ethers are described. The gas chromatographic separation of the L-fucose containing oligosaccharides was performed on Silicone SE 30. The sialic acid containing sugars were separated on DEXSIL 300. The correlations between oligosaccharide structures and mass spectrometric fragmentation patterns are discussed."}
{"id": "PMID:241173", "title": "[Dissociation and reassociation of poliovirus. I. Effect of urea on the virion].", "content": "Poliovirus is dissociated by urea in the presence of mercaptoethanol or dithiothreitol into RNA and protein(s). Differences exist in the sensitivity of poliovirus type I, II or III toward these agents. The decrease in infectivity titer of the virion is in the range of 10(9). After appropriate dissociation no infectious virions are found in urea-treated poliovirus concentrates. The released viral RNA is infectious. Its infectivity (1 times 10(6) PFU/mug RNA) is comparable to that of phenol extracted RNA. Therefore, urea dissociation is a fast and reliable method for the preparation of infectious poliovirus RNA even at the microliter scale. The dissociation of poliovirus is dependent upon the concentration, temperature and pH. The decrease in virion infectivity is time dependent. It is preceded by a lag phase of different lengths for poliovirus type I, II or III. During the lag phase the virion undergoes configurational changes without losing infectivity. From the observed hyperchromic effect is it obvious that the secondary structure of the RNA inside the virion breaks down, giving rise to expanded forms of poliovirus particles. After the lag phase the RNA is released and the empty capsid dissociated into the appropriate polypeptides.", "contents": "[Dissociation and reassociation of poliovirus. I. Effect of urea on the virion]. Poliovirus is dissociated by urea in the presence of mercaptoethanol or dithiothreitol into RNA and protein(s). Differences exist in the sensitivity of poliovirus type I, II or III toward these agents. The decrease in infectivity titer of the virion is in the range of 10(9). After appropriate dissociation no infectious virions are found in urea-treated poliovirus concentrates. The released viral RNA is infectious. Its infectivity (1 times 10(6) PFU/mug RNA) is comparable to that of phenol extracted RNA. Therefore, urea dissociation is a fast and reliable method for the preparation of infectious poliovirus RNA even at the microliter scale. The dissociation of poliovirus is dependent upon the concentration, temperature and pH. The decrease in virion infectivity is time dependent. It is preceded by a lag phase of different lengths for poliovirus type I, II or III. During the lag phase the virion undergoes configurational changes without losing infectivity. From the observed hyperchromic effect is it obvious that the secondary structure of the RNA inside the virion breaks down, giving rise to expanded forms of poliovirus particles. After the lag phase the RNA is released and the empty capsid dissociated into the appropriate polypeptides."}
{"id": "PMID:241178", "title": "[Synthetic medium for testing of susceptibility. II. Susceptibility of bacteria to sulphonamides (author's transl)].", "content": "A comparative study of 9 media for testing the susceptibility of bacteria to 7 sulphonamides has been carried out. The evaluated culture-media included 4 \"Mueller Hinton\" media (MH), 4 others based on the formula of the \"Diagnostic Sensitivity Test\" agar base (D.S.T.) and a \"Synthetic Medium\" (SM) which has been developed in our laboratory. MH and D.S.T. culture-media have been supplied by 4 manufacturing companies in Europe and USA. A total number of 21 bacterial cultures have been employed. The included species belong to the gram negative genera Citrobacter, Escherichia, Klebsiella, Proteus, Salmonella, Serratia and Shigella, and to the gram positive genus Streptococcus. Sulphafurazole, sulphasomidine, sulphamethoxazole, sulphamethoxypyridazine, sulphadimethoxine, sulphaphenazole and sulphamethoxydiazine have been investigated. SM proved to be clearly superior to the other 8 culture-media mentioned above. Just one MH afforded good results. The 3 other MH and 2 D.S.T. media were not quite satisfactory. The two remaining D.S.T. media were unsuitable. Moreover, the activity of the tested sulphonamides was not equally high against the concerned bacteria. The author discussed the significance of the inoculum-size and of competitive and noncompetitive sulphonamide-antagonists in commercial culture-media and the difficulties they raise by the interpretation of the results.", "contents": "[Synthetic medium for testing of susceptibility. II. Susceptibility of bacteria to sulphonamides (author's transl)]. A comparative study of 9 media for testing the susceptibility of bacteria to 7 sulphonamides has been carried out. The evaluated culture-media included 4 \"Mueller Hinton\" media (MH), 4 others based on the formula of the \"Diagnostic Sensitivity Test\" agar base (D.S.T.) and a \"Synthetic Medium\" (SM) which has been developed in our laboratory. MH and D.S.T. culture-media have been supplied by 4 manufacturing companies in Europe and USA. A total number of 21 bacterial cultures have been employed. The included species belong to the gram negative genera Citrobacter, Escherichia, Klebsiella, Proteus, Salmonella, Serratia and Shigella, and to the gram positive genus Streptococcus. Sulphafurazole, sulphasomidine, sulphamethoxazole, sulphamethoxypyridazine, sulphadimethoxine, sulphaphenazole and sulphamethoxydiazine have been investigated. SM proved to be clearly superior to the other 8 culture-media mentioned above. Just one MH afforded good results. The 3 other MH and 2 D.S.T. media were not quite satisfactory. The two remaining D.S.T. media were unsuitable. Moreover, the activity of the tested sulphonamides was not equally high against the concerned bacteria. The author discussed the significance of the inoculum-size and of competitive and noncompetitive sulphonamide-antagonists in commercial culture-media and the difficulties they raise by the interpretation of the results."}
{"id": "PMID:241174", "title": "[Long-term toxicity of benorylate].", "content": "A long term study was carried out to determine the possible toxic effects of therapeutic doses of a suspension of benorilate on bone marrow, liver and kidneys in 33 patients with rheumatoid arthritis. 14 were male and 19 femal patients. 11 of the male and 14 of the female patients presented a positive rheumatoid factor. The duration of the treatment was first limited to 6 months. In 20 of the 33 patients duration of treatment was extended to 7 and 91/2 months. Three patients interrupted treatment after respectively 2, 3 and 5 months. Benorilate was given in a daily dosage varying from 6-8-12 g (as a suspension containing 40% benorilate). The following parameters were used to determine the effect of the drug on bone marrow: Hemoglobin, erythrocyte count, leucocyte count, thrombocyte count. Tests were done at regular intervals to determine a possible toxic effect on the kidney: urea nitrogen, uric acid, creatinine and urineanalysis were performed at regular intervals. To determine any possible hepatic toxicity, SGOT, SGPT, alkaline phosphatase and prothrombin time were done at regular intervals. On the basis of the laboratory results, no toxicity could be demonstrated in bone marrow, liver and kidneys when benorilate was given in therapeutic doses for the treatment of rheumatoid arthritis. Rare temporary abnormal laboratory values are not statistically significant and can be considered part of systemic involvement secondary to rheumatoid arthritis. The combination of the two active substances of benorilate decreases to a minimum on the one hand the above mentioned side effects and on the other potentiates the therapeutic and especially the analgetic effect. After resorption, the preparation is hydrolized in the plasma to acetylic salicylic acid and paracetamol. The hydrolysis takes place in the gastrointestinal tract which probably explains why the drug is so well tolerated.", "contents": "[Long-term toxicity of benorylate]. A long term study was carried out to determine the possible toxic effects of therapeutic doses of a suspension of benorilate on bone marrow, liver and kidneys in 33 patients with rheumatoid arthritis. 14 were male and 19 femal patients. 11 of the male and 14 of the female patients presented a positive rheumatoid factor. The duration of the treatment was first limited to 6 months. In 20 of the 33 patients duration of treatment was extended to 7 and 91/2 months. Three patients interrupted treatment after respectively 2, 3 and 5 months. Benorilate was given in a daily dosage varying from 6-8-12 g (as a suspension containing 40% benorilate). The following parameters were used to determine the effect of the drug on bone marrow: Hemoglobin, erythrocyte count, leucocyte count, thrombocyte count. Tests were done at regular intervals to determine a possible toxic effect on the kidney: urea nitrogen, uric acid, creatinine and urineanalysis were performed at regular intervals. To determine any possible hepatic toxicity, SGOT, SGPT, alkaline phosphatase and prothrombin time were done at regular intervals. On the basis of the laboratory results, no toxicity could be demonstrated in bone marrow, liver and kidneys when benorilate was given in therapeutic doses for the treatment of rheumatoid arthritis. Rare temporary abnormal laboratory values are not statistically significant and can be considered part of systemic involvement secondary to rheumatoid arthritis. The combination of the two active substances of benorilate decreases to a minimum on the one hand the above mentioned side effects and on the other potentiates the therapeutic and especially the analgetic effect. After resorption, the preparation is hydrolized in the plasma to acetylic salicylic acid and paracetamol. The hydrolysis takes place in the gastrointestinal tract which probably explains why the drug is so well tolerated."}
{"id": "PMID:241179", "title": "[Toxin production by enteropathogenic colibacilli in adult persons (author's transl)].", "content": "Culture filtrates of enteropathogenic strains of E. coli from adult patients with cholera-like diarrhoea produced a rhythm-disturbing effect when injected into isolated sacklets of rabbit ileum. This action was shown to be medium-dependant. It could not be elicited by cultures grown in synthetic medium. Meat extract cultures gave variable results, but the gut movements could be irritated regularly when cultures were grown in a casamino acids - yeast extract medium (table, figure). This activity which was not associated with non-pathogenic strains appeared in the beginning of the stationary phase of growth. The factor responsible for the dysrhythmic effect could be precipitated by ammonium sulphate, was dialysable, withstood boiling for 10 minutes (figure) and treatment with trypsin, chymotrypsin and pancreatin. Antisera prepared against culture filtrates of strain 10407 containing agglutinating and vascular permeability neutralizing antibodies did not neutralize the gut irritating effect efficiently. We conclude that the factor of our assay system is perhaps closely related to the heat-stable enterotoxin described by other authors concerned by E. coli enterotoxins.", "contents": "[Toxin production by enteropathogenic colibacilli in adult persons (author's transl)]. Culture filtrates of enteropathogenic strains of E. coli from adult patients with cholera-like diarrhoea produced a rhythm-disturbing effect when injected into isolated sacklets of rabbit ileum. This action was shown to be medium-dependant. It could not be elicited by cultures grown in synthetic medium. Meat extract cultures gave variable results, but the gut movements could be irritated regularly when cultures were grown in a casamino acids - yeast extract medium (table, figure). This activity which was not associated with non-pathogenic strains appeared in the beginning of the stationary phase of growth. The factor responsible for the dysrhythmic effect could be precipitated by ammonium sulphate, was dialysable, withstood boiling for 10 minutes (figure) and treatment with trypsin, chymotrypsin and pancreatin. Antisera prepared against culture filtrates of strain 10407 containing agglutinating and vascular permeability neutralizing antibodies did not neutralize the gut irritating effect efficiently. We conclude that the factor of our assay system is perhaps closely related to the heat-stable enterotoxin described by other authors concerned by E. coli enterotoxins."}
{"id": "PMID:241180", "title": "[Toxigenesis of Clostridium novyi type A. 2. Communication: Extraction alpha-toxin from the cells by hypertonic buffers (author's transl)].", "content": "Great amounts of alpha-toxin produced by Cl. novyi type A and accumulated within the cell can be extracted by 0,2M sodium citrate buffer (pH 7,7) during the course of 2 to 5 days at 37 degrees C. Physiological saline, 0,1 M sodium citrate buffer (pH 7,7) and 0,05 to 0,2 M EDTA-buffers (pH 7,7) were not effective for complete extraction. During the process of extraction the lattice like structure of the peripheral part of the Cl. novyi cell wall was partially destroyed. The lattice is supposed to be a diffusion barrier for the toxin and may be regarded as one reason for the toxin accumulation in Cl. novyi.", "contents": "[Toxigenesis of Clostridium novyi type A. 2. Communication: Extraction alpha-toxin from the cells by hypertonic buffers (author's transl)]. Great amounts of alpha-toxin produced by Cl. novyi type A and accumulated within the cell can be extracted by 0,2M sodium citrate buffer (pH 7,7) during the course of 2 to 5 days at 37 degrees C. Physiological saline, 0,1 M sodium citrate buffer (pH 7,7) and 0,05 to 0,2 M EDTA-buffers (pH 7,7) were not effective for complete extraction. During the process of extraction the lattice like structure of the peripheral part of the Cl. novyi cell wall was partially destroyed. The lattice is supposed to be a diffusion barrier for the toxin and may be regarded as one reason for the toxin accumulation in Cl. novyi."}
{"id": "PMID:241181", "title": "[Practical considerations on treatment with antipsychotic preparations].", "content": "On the basis of a study of several hundred patients using the method of a double blind control the author showed the possibility of a successful maintenance treatment using intermittent dosage schedules with a marked reduction in the administration of antiparkinsonic agents. It is also demonstrated that patients under the age of 40 currently hospitalized less than 10 years on high doses of chlorpromazine in addition to showing generalized symptom reduction showed significant improvement in areas of social adjustment.", "contents": "[Practical considerations on treatment with antipsychotic preparations]. On the basis of a study of several hundred patients using the method of a double blind control the author showed the possibility of a successful maintenance treatment using intermittent dosage schedules with a marked reduction in the administration of antiparkinsonic agents. It is also demonstrated that patients under the age of 40 currently hospitalized less than 10 years on high doses of chlorpromazine in addition to showing generalized symptom reduction showed significant improvement in areas of social adjustment."}
{"id": "PMID:241182", "title": "[Rational utilization of the major tranquilizers].", "content": "The author examined a group of drug-free patients who during the subsequent period of I month received chlorpromazine. These patients were studied for the chlorpromazine content in the blood, pupilzise, handwriting test, EEG and mental state. The level of chlorpromasine was maximal in the first 2 weeks and then declined. Changes in the peripheral autonomic measures correlated with those in the plasma levels and with an increased liver hydrozylation. Changes in the central measures were inconsistent. A 3-week treatment with phenobarbitone and antiparkinsonic drugs accelerated the metabolism of chlorpromazine. An increased metabolism of chlorpromazine in the intestine and liver may be the cause of the patients' resistanec to chlorpromazine therapy.", "contents": "[Rational utilization of the major tranquilizers]. The author examined a group of drug-free patients who during the subsequent period of I month received chlorpromazine. These patients were studied for the chlorpromazine content in the blood, pupilzise, handwriting test, EEG and mental state. The level of chlorpromasine was maximal in the first 2 weeks and then declined. Changes in the peripheral autonomic measures correlated with those in the plasma levels and with an increased liver hydrozylation. Changes in the central measures were inconsistent. A 3-week treatment with phenobarbitone and antiparkinsonic drugs accelerated the metabolism of chlorpromazine. An increased metabolism of chlorpromazine in the intestine and liver may be the cause of the patients' resistanec to chlorpromazine therapy."}
{"id": "PMID:241183", "title": "Fluorescence of tyrosine residues in the basic trypsin inhibitor from bovine lungs.", "content": "Fluorescence of 0.02 - 2% water solutions of basic trypsin inhibitor in the temperature range of 5 - 80 degrees C at pH 2.6 and 7.7 has been investigated and changes of the relative emission at 302.5 and 307.5 nm analysed. The observed fluorescent effects were ascribed to individual tyrosine residues in the protein molecule. The temperature-dependent changes of spectra were discussed in terms of possible influence of molecular aggregation in solution at higher protein concentrations.", "contents": "Fluorescence of tyrosine residues in the basic trypsin inhibitor from bovine lungs. Fluorescence of 0.02 - 2% water solutions of basic trypsin inhibitor in the temperature range of 5 - 80 degrees C at pH 2.6 and 7.7 has been investigated and changes of the relative emission at 302.5 and 307.5 nm analysed. The observed fluorescent effects were ascribed to individual tyrosine residues in the protein molecule. The temperature-dependent changes of spectra were discussed in terms of possible influence of molecular aggregation in solution at higher protein concentrations."}
{"id": "PMID:241184", "title": "[Microcalorimetric determination of thermochemical parameters of the phosphofructokinase reaction].", "content": "A calorimetric procedure for determining deltaH, deltaG, deltaS and Keq of a bimolecular reaction with two or more products is described. By using this method the thermodynamic parameters of the phosphofructokinase reaction are determined. At pH 7.0 and 25 degrees C a reaction enthalpy of-6.96kcal/mole was found after correction for the neutralization enthalpy of the buffer and of the enthalpy difference of the magnesium complexes of ATP and ADP, respectively. The free energy of the phosphofructokinase reaction has been found under these conditions to be -3.96kcal/mole.", "contents": "[Microcalorimetric determination of thermochemical parameters of the phosphofructokinase reaction]. A calorimetric procedure for determining deltaH, deltaG, deltaS and Keq of a bimolecular reaction with two or more products is described. By using this method the thermodynamic parameters of the phosphofructokinase reaction are determined. At pH 7.0 and 25 degrees C a reaction enthalpy of-6.96kcal/mole was found after correction for the neutralization enthalpy of the buffer and of the enthalpy difference of the magnesium complexes of ATP and ADP, respectively. The free energy of the phosphofructokinase reaction has been found under these conditions to be -3.96kcal/mole."}
{"id": "PMID:241185", "title": "[Studies on bradykinin-binding cell fractions. 1. Characterization of kininase activity of the microsomal and membrane fraction from the rat uterus].", "content": "In the membrane fraction of rat uterus, kinin-destroying activity was found and characterized as kininase II by means of several kininase inhibitors. It could be shown that sudies of bradykinin-receptor interactions requires the use of kininase inhibitors like phenanthroline or the use of a stable bradykinin analogue like [8-erythro-alpha-amino-beta-phenylbutyric acid]-bradykinin.", "contents": "[Studies on bradykinin-binding cell fractions. 1. Characterization of kininase activity of the microsomal and membrane fraction from the rat uterus]. In the membrane fraction of rat uterus, kinin-destroying activity was found and characterized as kininase II by means of several kininase inhibitors. It could be shown that sudies of bradykinin-receptor interactions requires the use of kininase inhibitors like phenanthroline or the use of a stable bradykinin analogue like [8-erythro-alpha-amino-beta-phenylbutyric acid]-bradykinin."}
{"id": "PMID:241186", "title": "Studies on 17 beta-hydroxysteroid dehydrogenase in human endometrium and endometrial carcinoma. III. Partial purification and characterization of the microsomal enzyme.", "content": "Microsomal 17 beta-hydroxysteroid dehydrogenase obtained from the human secretory endometrium (17 beta-HSD) was solubilized with triton X-100. A 4-fold purification was achieved by ammonium sulphate precipitation and isoelectric focusing. In the presence of glycerol the partially purified enzyme was stable at 4 degrees C for at least 48 h. Using crude microsomes, the conversion of oestradiol to oestrone was linear with time and with the concentration of protein. The optimum temperature was approximately 40 degrees C and the optimum pH 9.4. For the reduction of oestrone the optimum pH was 6.5. With NAD, oestradiol was oxidized approximately three times more rapidly than with NADP. Km-values for oestradiol were nearly the same in endometrial carcinoma and in proliferative and secretory endometrium (i.e. approximately 3 X 10(-6) M). The maximal velocity was highest in secretory endometrium. Testosterone and androstenedione could also serve as substrates but they were interconverted more slowly than oestradiol and oestrone. Sulphhydryl groups were shown to be essential for catalysis.", "contents": "Studies on 17 beta-hydroxysteroid dehydrogenase in human endometrium and endometrial carcinoma. III. Partial purification and characterization of the microsomal enzyme. Microsomal 17 beta-hydroxysteroid dehydrogenase obtained from the human secretory endometrium (17 beta-HSD) was solubilized with triton X-100. A 4-fold purification was achieved by ammonium sulphate precipitation and isoelectric focusing. In the presence of glycerol the partially purified enzyme was stable at 4 degrees C for at least 48 h. Using crude microsomes, the conversion of oestradiol to oestrone was linear with time and with the concentration of protein. The optimum temperature was approximately 40 degrees C and the optimum pH 9.4. For the reduction of oestrone the optimum pH was 6.5. With NAD, oestradiol was oxidized approximately three times more rapidly than with NADP. Km-values for oestradiol were nearly the same in endometrial carcinoma and in proliferative and secretory endometrium (i.e. approximately 3 X 10(-6) M). The maximal velocity was highest in secretory endometrium. Testosterone and androstenedione could also serve as substrates but they were interconverted more slowly than oestradiol and oestrone. Sulphhydryl groups were shown to be essential for catalysis."}
{"id": "PMID:241187", "title": "Evaluation of a new method for the intragastric titration of gastric juice.", "content": "A new method for the intragastric titration of hydrochloric acid with a pH sensitive telemetric antimone electrode connected via a receiver to an electronic trigger, which regulates a pump for the inflow of 1 M KHCO3 solution, was evaluated in 22 achlorhydric patients by a series of intragastric instillations of 0.1 N HCl. In vitro this procedure presented a high precision (r = 0.99). Under in vivo conditions a significant correlationship (r = 0.84, p = 0.001) between the input of hydrochloric acid and bicarbonate in a range from 1.4 to 16.7 mEq/30 min could be established in non-operated subjects. The average coefficient of variation was 34%. In subjects with partial gastrectomy (Billroth II) overtitration of 100% (y = 2.1 x -1.7, r = 0.78, p = 0.001) was recorded, suggesting an increased loss of bicarbonate related to the accelerated gastric evacuation.", "contents": "Evaluation of a new method for the intragastric titration of gastric juice. A new method for the intragastric titration of hydrochloric acid with a pH sensitive telemetric antimone electrode connected via a receiver to an electronic trigger, which regulates a pump for the inflow of 1 M KHCO3 solution, was evaluated in 22 achlorhydric patients by a series of intragastric instillations of 0.1 N HCl. In vitro this procedure presented a high precision (r = 0.99). Under in vivo conditions a significant correlationship (r = 0.84, p = 0.001) between the input of hydrochloric acid and bicarbonate in a range from 1.4 to 16.7 mEq/30 min could be established in non-operated subjects. The average coefficient of variation was 34%. In subjects with partial gastrectomy (Billroth II) overtitration of 100% (y = 2.1 x -1.7, r = 0.78, p = 0.001) was recorded, suggesting an increased loss of bicarbonate related to the accelerated gastric evacuation."}
{"id": "PMID:241188", "title": "[Histochemical evidence of aminotransferases. II. Localization of aminotransferases in the medulla spinalis and metencephalon of the rat (author's transl)].", "content": "The cytochemical and topochemical localization of 10 aminotransferases have been studied in a serial slices through the spinal cord, medulla oblongata, pons and cerebellum of the rat. In the gray matter a high enzyme activity was observed. The reaction product was localized in the cells and the surrounding neuropil. The cell nuclei were found negativ. In some nuclei aminotransferase activity was higher in the neurons than in the neuropil. In the other nuclei there were no recognizable differences in staining intensity between the neurons and the neuropil. The nerve cells of spinal cord and reticular formation, nuclei n. hypoglossi and n. facialis, nucl. vestibularis lateralis and the Purkinje cells exhibited particularly high aminotransferase activity.", "contents": "[Histochemical evidence of aminotransferases. II. Localization of aminotransferases in the medulla spinalis and metencephalon of the rat (author's transl)]. The cytochemical and topochemical localization of 10 aminotransferases have been studied in a serial slices through the spinal cord, medulla oblongata, pons and cerebellum of the rat. In the gray matter a high enzyme activity was observed. The reaction product was localized in the cells and the surrounding neuropil. The cell nuclei were found negativ. In some nuclei aminotransferase activity was higher in the neurons than in the neuropil. In the other nuclei there were no recognizable differences in staining intensity between the neurons and the neuropil. The nerve cells of spinal cord and reticular formation, nuclei n. hypoglossi and n. facialis, nucl. vestibularis lateralis and the Purkinje cells exhibited particularly high aminotransferase activity."}
{"id": "PMID:241189", "title": "[The mucous secretion anisotropy of the sublingual gland of the guinea-pig by means of topo-optical histochemical reaction (author's transl)].", "content": "The authors study the mucous secretion of sublingual gland of the guinea-pig by means of topo-optical histochemical reactions with polarized light. They show a \"paracristalline\" organization of glucidic and protidic portion of these macromolecules. The results are discussed and compared with those of the literature.", "contents": "[The mucous secretion anisotropy of the sublingual gland of the guinea-pig by means of topo-optical histochemical reaction (author's transl)]. The authors study the mucous secretion of sublingual gland of the guinea-pig by means of topo-optical histochemical reactions with polarized light. They show a \"paracristalline\" organization of glucidic and protidic portion of these macromolecules. The results are discussed and compared with those of the literature."}
{"id": "PMID:241190", "title": "[Histochemical investigations in the experimental unilateral cryptorchism of the dog after HCG-treatment (author's transl)].", "content": "The behavior of various enzymes in the orthotopic and dystopic dog testis was examined under the conditions of experimental unilateral cryptorchism after HCG-treatment over a period of 3 months. The following findings could be obtained: 1. Under the HCG-application the orthotopic impuberal testis there was a change of behavior of the enzyme in the tubuli and Leydig-cells in comparison with test animals. A loss of LDH of the epithelium of the tubuli can be avoided through HCG-treatment. 2. In the dystopic testis of the impuberal animal, HCG cannot avoid this loss of LDH in the epithelium of the tubuli. In the Leydig cell complexes the Glucose-6-Phosphate-Dehydrogenase shows an increase of activity. 3. In the Leydig cell complexes of the impuberal testis an apparent loss of LDH is noticeable in the epithelium of the tubuli, while the non-specific esterase, SDH and the Glucose-6-Phosphate Dehydrogenase increases in activity. The activity of the Leydig cell complexes shows the expected stimulation. The present results prove that under a large dose of HCG-treatment can lead to different changes in the enzymes of the orthotopic testis of dogs.", "contents": "[Histochemical investigations in the experimental unilateral cryptorchism of the dog after HCG-treatment (author's transl)]. The behavior of various enzymes in the orthotopic and dystopic dog testis was examined under the conditions of experimental unilateral cryptorchism after HCG-treatment over a period of 3 months. The following findings could be obtained: 1. Under the HCG-application the orthotopic impuberal testis there was a change of behavior of the enzyme in the tubuli and Leydig-cells in comparison with test animals. A loss of LDH of the epithelium of the tubuli can be avoided through HCG-treatment. 2. In the dystopic testis of the impuberal animal, HCG cannot avoid this loss of LDH in the epithelium of the tubuli. In the Leydig cell complexes the Glucose-6-Phosphate-Dehydrogenase shows an increase of activity. 3. In the Leydig cell complexes of the impuberal testis an apparent loss of LDH is noticeable in the epithelium of the tubuli, while the non-specific esterase, SDH and the Glucose-6-Phosphate Dehydrogenase increases in activity. The activity of the Leydig cell complexes shows the expected stimulation. The present results prove that under a large dose of HCG-treatment can lead to different changes in the enzymes of the orthotopic testis of dogs."}
{"id": "PMID:241191", "title": "Relationship between pycnotic indec Qp as a result of oxygen supply and similar indices as a result of in vitro offer of cytochrome c and NADP in psychiatry.", "content": "The authors follow up on their previous studies of morphological changes in the properties of white blood cells represented by the oxygen pycnotic index Qp in patients with the schizophrenic syndrome. Several years of research made it obvious to them that this index remains generally unaffected by drugs administered during the treatment although the patient does show a pronounced clinical change. They decided to substitute the offer of oxygen by adding a supply of cytochrome c and NADP, i.e. by substances that give a boost to the oxidoreduction processes within the cell. They found the pycnotic quotient, based on cytochrome c, and - to an even greater degree - the NADP-based quotient to be more responsive to differences in the seriousness of the disease than the oxygen quotient.", "contents": "Relationship between pycnotic indec Qp as a result of oxygen supply and similar indices as a result of in vitro offer of cytochrome c and NADP in psychiatry. The authors follow up on their previous studies of morphological changes in the properties of white blood cells represented by the oxygen pycnotic index Qp in patients with the schizophrenic syndrome. Several years of research made it obvious to them that this index remains generally unaffected by drugs administered during the treatment although the patient does show a pronounced clinical change. They decided to substitute the offer of oxygen by adding a supply of cytochrome c and NADP, i.e. by substances that give a boost to the oxidoreduction processes within the cell. They found the pycnotic quotient, based on cytochrome c, and - to an even greater degree - the NADP-based quotient to be more responsive to differences in the seriousness of the disease than the oxygen quotient."}
{"id": "PMID:241192", "title": "Cardiovascular effects of benzquinamide in man.", "content": "Benzquinamide HCl, a new antiemetic agent, was studied in twelve healthy volunteers. Each subject received intravenously both benzquinamide (0.7 mg/kg) and placebo in a randomized, double-blind crossover manner. Cardiac output and arterial pressure, arterial blood gases, respiration (tidal volume and rate), and oxygen consumption were measured twice before drug administration and at 5, 10, 20 and 30 min after injection. Intra-arterial pressure increased significantly (P less than 0.005) at 5 min (12.6%) and 10 min (8.6%) following benzquinamide. Likewise, peripheral vascular resistance increased significantly (P less than 0.005) at 5 min (14.3%) and 10 min (8.8%) post-injection. Cardiac output, stroke volume and heart rate remained essentially unchanged. A significant increase (P less than 0.025) in respiratory rate was observed at 10 min (8.7%) and 20 min (12.6%) following benzquinamide. Values for the arterial Po2, Pco2, and pH showed no significant changes. It is considered that the effect of benzquinamide in increasing intra-arterial pressure is due to the increased peripheral vascular resistance.", "contents": "Cardiovascular effects of benzquinamide in man. Benzquinamide HCl, a new antiemetic agent, was studied in twelve healthy volunteers. Each subject received intravenously both benzquinamide (0.7 mg/kg) and placebo in a randomized, double-blind crossover manner. Cardiac output and arterial pressure, arterial blood gases, respiration (tidal volume and rate), and oxygen consumption were measured twice before drug administration and at 5, 10, 20 and 30 min after injection. Intra-arterial pressure increased significantly (P less than 0.005) at 5 min (12.6%) and 10 min (8.6%) following benzquinamide. Likewise, peripheral vascular resistance increased significantly (P less than 0.005) at 5 min (14.3%) and 10 min (8.8%) post-injection. Cardiac output, stroke volume and heart rate remained essentially unchanged. A significant increase (P less than 0.025) in respiratory rate was observed at 10 min (8.7%) and 20 min (12.6%) following benzquinamide. Values for the arterial Po2, Pco2, and pH showed no significant changes. It is considered that the effect of benzquinamide in increasing intra-arterial pressure is due to the increased peripheral vascular resistance."}
{"id": "PMID:241193", "title": "Effects of hypothermia and hyperthermia on brain energy metabolism.", "content": "The influence of elevated and reduced body temperatures upon the metabolic state of the brain was evaluated from the tissue concentrations of phosphocreatine (PCr) ATP, ADP and AMP and from the concentrations of glucose, lactate and pyruvate in immobilized and artificially ventilated rats anesthetized with 70% N2O. The results were compared to the results obtained in normothermic animals. It was found that rats with body temperatures of 32 degrees and 22 degrees C had the same brain tissue concentrations of high energy phosphates and the same adenylate energy charge as the controls, but hypothermia led to a progressive decrease of both cerebral and arterial lactate and pyruvate concentrations. A metabolic acidosis but no excess lactate appeared in the blood. At a body temperature of 42 degrees C, the metabolic pattern in the brain agreed with a state of hypoxia at a time when there was no sign of substrate depletion. Arterial blood showed excess lactate which may indicate an inadequacy of the oxygen supply also to other tissues.", "contents": "Effects of hypothermia and hyperthermia on brain energy metabolism. The influence of elevated and reduced body temperatures upon the metabolic state of the brain was evaluated from the tissue concentrations of phosphocreatine (PCr) ATP, ADP and AMP and from the concentrations of glucose, lactate and pyruvate in immobilized and artificially ventilated rats anesthetized with 70% N2O. The results were compared to the results obtained in normothermic animals. It was found that rats with body temperatures of 32 degrees and 22 degrees C had the same brain tissue concentrations of high energy phosphates and the same adenylate energy charge as the controls, but hypothermia led to a progressive decrease of both cerebral and arterial lactate and pyruvate concentrations. A metabolic acidosis but no excess lactate appeared in the blood. At a body temperature of 42 degrees C, the metabolic pattern in the brain agreed with a state of hypoxia at a time when there was no sign of substrate depletion. Arterial blood showed excess lactate which may indicate an inadequacy of the oxygen supply also to other tissues."}
{"id": "PMID:241194", "title": "Pulmonary and circulatory reactions during total hip replacement surgery.", "content": "The pulmonary and circulatory reactions to insertion of the acetabular and of the femoral prosthesis were studied during total hip replacement surgery in 22 patients with osteoarthrosis. The patients were given lumbar epidural analgesia and were divided into two groups. One group of 15 awake patients breathed air spontaneously (group A). The other group of seven patinets received additional anaesthesia with controlled ventilation with air (group B). This permitted an evaluation of the influence of the ventilatory pattern on the pulmonary and circulatory reactions to the surgical events. The greatest alterations were observed following impaction of the femoral prosthesis. This event caused the following statistically significant changes in both groups: An increase in total pulmonary venous admixture (from a mean value of 6.8 to 12.2% in group A and from 8.2 to 10.5% in group B) and a decrease in arterial oxygen tension (group A: 80.3 to 71.5 mmHg; group B: 82.6 to 76.9 mmHg); an increase in pulmonary vascular resistance (group A: 122 to 155 dyn -s- cm-5; group B: 129 to 164 dyn -s- cm-5) and an increase in mean pulmonary arterial pressure (group A: 17.3 to 19.0 mmHg; group B: 21.8 to 24.4 mmHg). Furtheremore, within the first 2 min after impaction a distinct transient rise in mean pulmonary arterial pressure by 2-4 mmHg was noted in a few patients, and in many patients the mean systemic arterial pressure decreased by 5 mmHg or more. No significant changes were found in cardiac output, pulmonary capillary wedge pressure, oxygen uptake, mixed venous oxygen tension, acid-base values, ratio of total dead space to tidal volume, or total airway resistance. The above findings indicate a tendency to pulmonary vascular and peripheral airway constriction leading to transient ventilation/perfusion disturbances and a decrease in arterial oxygen tension, and peripheral vasodilatation leading to a transient decrease in systemic arterial pressure.", "contents": "Pulmonary and circulatory reactions during total hip replacement surgery. The pulmonary and circulatory reactions to insertion of the acetabular and of the femoral prosthesis were studied during total hip replacement surgery in 22 patients with osteoarthrosis. The patients were given lumbar epidural analgesia and were divided into two groups. One group of 15 awake patients breathed air spontaneously (group A). The other group of seven patinets received additional anaesthesia with controlled ventilation with air (group B). This permitted an evaluation of the influence of the ventilatory pattern on the pulmonary and circulatory reactions to the surgical events. The greatest alterations were observed following impaction of the femoral prosthesis. This event caused the following statistically significant changes in both groups: An increase in total pulmonary venous admixture (from a mean value of 6.8 to 12.2% in group A and from 8.2 to 10.5% in group B) and a decrease in arterial oxygen tension (group A: 80.3 to 71.5 mmHg; group B: 82.6 to 76.9 mmHg); an increase in pulmonary vascular resistance (group A: 122 to 155 dyn -s- cm-5; group B: 129 to 164 dyn -s- cm-5) and an increase in mean pulmonary arterial pressure (group A: 17.3 to 19.0 mmHg; group B: 21.8 to 24.4 mmHg). Furtheremore, within the first 2 min after impaction a distinct transient rise in mean pulmonary arterial pressure by 2-4 mmHg was noted in a few patients, and in many patients the mean systemic arterial pressure decreased by 5 mmHg or more. No significant changes were found in cardiac output, pulmonary capillary wedge pressure, oxygen uptake, mixed venous oxygen tension, acid-base values, ratio of total dead space to tidal volume, or total airway resistance. The above findings indicate a tendency to pulmonary vascular and peripheral airway constriction leading to transient ventilation/perfusion disturbances and a decrease in arterial oxygen tension, and peripheral vasodilatation leading to a transient decrease in systemic arterial pressure."}
{"id": "PMID:241195", "title": "The effect of controlled halothane anaesthesia on splanchnic oxygen consumption in the dog.", "content": "The influence of halothane ansesthesia on splanchnic oxygen flow and oxygen uptake was studied in seven dogs. Mean oxygen supply to the liver and the portally-drained tissues decreased significantly to 44% and 53% of control values, respectively, while mena oxygen consumption diminished insignificantly to 68% and 82% of control values, respectively. There was a fall in the oxygen flow/oxygen consumption ratio in all animals following halothane. The relatively unimpaired oxygen uptake, in spite of a diminished oxygen supply, led to an increased extraction of oxygen by the tissues. Some factors affecting oxygen utilisation during halothane anaesthesia are discussed.", "contents": "The effect of controlled halothane anaesthesia on splanchnic oxygen consumption in the dog. The influence of halothane ansesthesia on splanchnic oxygen flow and oxygen uptake was studied in seven dogs. Mean oxygen supply to the liver and the portally-drained tissues decreased significantly to 44% and 53% of control values, respectively, while mena oxygen consumption diminished insignificantly to 68% and 82% of control values, respectively. There was a fall in the oxygen flow/oxygen consumption ratio in all animals following halothane. The relatively unimpaired oxygen uptake, in spite of a diminished oxygen supply, led to an increased extraction of oxygen by the tissues. Some factors affecting oxygen utilisation during halothane anaesthesia are discussed."}
{"id": "PMID:241197", "title": "Etidocaine in intercostal nerve block for pain relief after thoracotomy; a comparison with bupivacaine.", "content": "For pain relief after thoracotomy, intercostal nerve block with etidocaine 1% and bupivacaine 0.5%, both containing adrenaline 5 mug/ml, was used. Duration of skin analgesia for sharp pain was around 11 hours for both solutions. Post-operative pain was noted 6 and 5 hours after injection for etidocaine and bupivacaine respectively. No pathological changes in acid-base balance or ventilation were observed. Peak expiratory flow decreased to 35-40% of the pre-operative values and remained at this level for about 12 hours. Arterial and venous blood levels of the local anaesthetics were low and no signs of toxicity were noted. All patients experienced a certain pain relief from the blocks. Because of shoulder pain in some patients intercostal nerve block alone does not seem to be a perfect post-operative method for pain relief after thoracotomies.", "contents": "Etidocaine in intercostal nerve block for pain relief after thoracotomy; a comparison with bupivacaine. For pain relief after thoracotomy, intercostal nerve block with etidocaine 1% and bupivacaine 0.5%, both containing adrenaline 5 mug/ml, was used. Duration of skin analgesia for sharp pain was around 11 hours for both solutions. Post-operative pain was noted 6 and 5 hours after injection for etidocaine and bupivacaine respectively. No pathological changes in acid-base balance or ventilation were observed. Peak expiratory flow decreased to 35-40% of the pre-operative values and remained at this level for about 12 hours. Arterial and venous blood levels of the local anaesthetics were low and no signs of toxicity were noted. All patients experienced a certain pain relief from the blocks. Because of shoulder pain in some patients intercostal nerve block alone does not seem to be a perfect post-operative method for pain relief after thoracotomies."}
{"id": "PMID:241200", "title": "Bacterial flora in relation to cataract extraction. I. Material, methods and preoperative flora.", "content": "The conjunctival flora of 499 patients was studied the day before cataract extraction, no antibiotics or chemotherapeutical agents had been used before admission. Staphylococcus albus was by far the most common micro-organism (95.4%), followed by corynebacteria (44%), Staphylococcus aureus (14.9%), gram-negative bacilli (7.8%) and pneumo-streptococci (4.4%). Corynebacteria was isolated more frequently in the presence of S. albus, while S. aureus and gram-negative bacilli were found more frequently in the absence of S. albus. No relationship could be demonstrated between the occurrence of pneumo-streptococci and S. albus. The flora of the nose and skin of the face were studied and compared with the conjunctival flora, and a similarity could be observed. Furthermore, strains of S. aureus isolated at the same time from the two or three regions, in most cases, showed the same bacterio-phage type complex. The conjunctival flora was further correlated with sex, age, season, and number of polymorphonuclear neutrophils recovered from the conjunctival fluid. The incidence of corynebacteria and gram-negative bacilli was found to be higher in males, while corynebacteria was the only organism to show seasonal variation, i.e. was isolated more frequently in the second and third quarters of the year. No correlation could be found between age or number of neutrophils.", "contents": "Bacterial flora in relation to cataract extraction. I. Material, methods and preoperative flora. The conjunctival flora of 499 patients was studied the day before cataract extraction, no antibiotics or chemotherapeutical agents had been used before admission. Staphylococcus albus was by far the most common micro-organism (95.4%), followed by corynebacteria (44%), Staphylococcus aureus (14.9%), gram-negative bacilli (7.8%) and pneumo-streptococci (4.4%). Corynebacteria was isolated more frequently in the presence of S. albus, while S. aureus and gram-negative bacilli were found more frequently in the absence of S. albus. No relationship could be demonstrated between the occurrence of pneumo-streptococci and S. albus. The flora of the nose and skin of the face were studied and compared with the conjunctival flora, and a similarity could be observed. Furthermore, strains of S. aureus isolated at the same time from the two or three regions, in most cases, showed the same bacterio-phage type complex. The conjunctival flora was further correlated with sex, age, season, and number of polymorphonuclear neutrophils recovered from the conjunctival fluid. The incidence of corynebacteria and gram-negative bacilli was found to be higher in males, while corynebacteria was the only organism to show seasonal variation, i.e. was isolated more frequently in the second and third quarters of the year. No correlation could be found between age or number of neutrophils."}
{"id": "PMID:241201", "title": "Bacterial flora in relation to cataract extraction. II. Peroperative flora.", "content": "The peroperative flora of 499 patients undergoing cataract extraction was studied with local bacterial cultures taken at the beginning and end of surgery and compared with the preoperative flora examined previously (Fahmy et al. 1975 b) on admission the day prior to surgery. The local application of a single dose of oxytetracycline - polymyxin B, approximately 18 hours before surgery, significantly reduced the incidence of bacteria at the time of surgery. However, 92% of the conjunctivas examined immediately before operation proved to harbour one or more kinds of microorganisms. Futhermore, 61% of the wound sites were found to be contaminated with bacteria at the conclusion of surgery. The reasons are discussed. The origin of Staphylococcus aureus isolated peroperatively from the conjunctiva and wound site was studied. The great majority of strains could be traced to the patient's own conjunctiva preoperatively. In a few cases S. aureus was traced to the patient's own nose, skin of face or to the surgeon's nose. The air of the wards and operating theatre as well as the hands and gloves of surgeons and assistant nurses apparently did not play any role as a source of S. aureus infection.", "contents": "Bacterial flora in relation to cataract extraction. II. Peroperative flora. The peroperative flora of 499 patients undergoing cataract extraction was studied with local bacterial cultures taken at the beginning and end of surgery and compared with the preoperative flora examined previously (Fahmy et al. 1975 b) on admission the day prior to surgery. The local application of a single dose of oxytetracycline - polymyxin B, approximately 18 hours before surgery, significantly reduced the incidence of bacteria at the time of surgery. However, 92% of the conjunctivas examined immediately before operation proved to harbour one or more kinds of microorganisms. Futhermore, 61% of the wound sites were found to be contaminated with bacteria at the conclusion of surgery. The reasons are discussed. The origin of Staphylococcus aureus isolated peroperatively from the conjunctiva and wound site was studied. The great majority of strains could be traced to the patient's own conjunctiva preoperatively. In a few cases S. aureus was traced to the patient's own nose, skin of face or to the surgeon's nose. The air of the wards and operating theatre as well as the hands and gloves of surgeons and assistant nurses apparently did not play any role as a source of S. aureus infection."}
{"id": "PMID:241202", "title": "Histochemical demonstration of an LNA-splitting enzyme in the cerebellum of the rat. A aminopeptidase-like reaction localized selectively in the granular layer with acid pH optimum.", "content": "Histochemical investigations of leucine aminopeptidase using LNA (L-leucyl-beta-napthylamide) as a substrate reveals a marked enzyme activity selectively localized to the granular layer with inconspicuous reaction in the stratum moleculare and the Purkinje cells in the rat cerebellum. The LNA-splitting enzyme differs from the well-known leucine aminopeptidase (LAP) by its optimum at pH 5.5. The necessary long incubation period used in the present study, and its focal precipitation of the enzyme reaction product in the same place, like acid phosphatases, in the granular layer, suggest a lysosomal localization. The functional role of the LNA-splitting enzyme has been discussed; it is considered that it is involved not only in the protein transformation for synaptic function, but may perhaps also play an important pathogenic role in necrosis, atrophy or even autolysis.", "contents": "Histochemical demonstration of an LNA-splitting enzyme in the cerebellum of the rat. A aminopeptidase-like reaction localized selectively in the granular layer with acid pH optimum. Histochemical investigations of leucine aminopeptidase using LNA (L-leucyl-beta-napthylamide) as a substrate reveals a marked enzyme activity selectively localized to the granular layer with inconspicuous reaction in the stratum moleculare and the Purkinje cells in the rat cerebellum. The LNA-splitting enzyme differs from the well-known leucine aminopeptidase (LAP) by its optimum at pH 5.5. The necessary long incubation period used in the present study, and its focal precipitation of the enzyme reaction product in the same place, like acid phosphatases, in the granular layer, suggest a lysosomal localization. The functional role of the LNA-splitting enzyme has been discussed; it is considered that it is involved not only in the protein transformation for synaptic function, but may perhaps also play an important pathogenic role in necrosis, atrophy or even autolysis."}
{"id": "PMID:241203", "title": "On histochemical enzyme changes in association with canalicular activity of alkaline phosphatase in human liver.", "content": "56 human liver biopsy specimens with insignificant or no histological changes, but with abnormally strong canalicular alkaline phosphatase activity, were studied histochemically for other enzyme changes. In comparison with normal specimens, more extensive and increased canalicular activity of gamma-glutamyl transferase, and increase of canalicular leucine aminopeptidase, was found, while the sinusoidal activity of the latter enzyme was decreased. Staining for adenosine triphosphatase regularly desclosed the normal pattern of sinusoidal and canalicular activity. The lysosomal enzymes, acid phosphatase and beta-glucuronidase, stained more intensely than ordinarily, while the reactions for enzymes present in the cytosol (lactic dehydrogenase), in the mitochondria (succinic dehydrogenase, imonoamine oxidase) and in the endoplasmic reticulum (glucose-6-phosphatase) were normal.", "contents": "On histochemical enzyme changes in association with canalicular activity of alkaline phosphatase in human liver. 56 human liver biopsy specimens with insignificant or no histological changes, but with abnormally strong canalicular alkaline phosphatase activity, were studied histochemically for other enzyme changes. In comparison with normal specimens, more extensive and increased canalicular activity of gamma-glutamyl transferase, and increase of canalicular leucine aminopeptidase, was found, while the sinusoidal activity of the latter enzyme was decreased. Staining for adenosine triphosphatase regularly desclosed the normal pattern of sinusoidal and canalicular activity. The lysosomal enzymes, acid phosphatase and beta-glucuronidase, stained more intensely than ordinarily, while the reactions for enzymes present in the cytosol (lactic dehydrogenase), in the mitochondria (succinic dehydrogenase, imonoamine oxidase) and in the endoplasmic reticulum (glucose-6-phosphatase) were normal."}
{"id": "PMID:241206", "title": "The effect of Ca++, Mg++ and H+ on the capillary permeability of the rete mirabile of the eel, Anguilla vulgaris L.", "content": "The effects of EDTA, and of varying pH on the capillary permeability in the rete mirabile have been investigated: EDTA had to be added to the perfusate in excess to the total content of Ca++ and Mg++ in plasma in order to elicit changes in the permeability. When exposed to sufficient amounts of EDTA, the capillary permeability to hydrophilic molecules increased several fold whereas the permeability to THO and lipid-soluble molecules remained unchanged. The increase in the permeability to high-molecular dextrans was delayed. When the EDTA-effect was maximal the mutual relationship between the permeabilities of THO and the lipid-insoluble molecules became close to the ratio between the corresponding free diffusion coefficients in water. During exposure to EDTA the content of K+ and Na+ of the rete tissue (mostly endothelial cells) became very similar to that of plasma. Similar effects were obtained when the rete was perfused with plasma having a pH below 4 or above 9. The EDTA-effect was reversible during its initial stage. Perfusions with plasma in which Ca and Mg had been removed by dialysis at pH 3.5 were performed. When an EDTA-effect had been induced with this type of perfusates, it could be reversed by addition of equimolar amounts of either Ca++ or Mg++. This indicates Ca++ and Mg++ to be equally important in order to assure normal permeability properties of the capillary membrane.", "contents": "The effect of Ca++, Mg++ and H+ on the capillary permeability of the rete mirabile of the eel, Anguilla vulgaris L. The effects of EDTA, and of varying pH on the capillary permeability in the rete mirabile have been investigated: EDTA had to be added to the perfusate in excess to the total content of Ca++ and Mg++ in plasma in order to elicit changes in the permeability. When exposed to sufficient amounts of EDTA, the capillary permeability to hydrophilic molecules increased several fold whereas the permeability to THO and lipid-soluble molecules remained unchanged. The increase in the permeability to high-molecular dextrans was delayed. When the EDTA-effect was maximal the mutual relationship between the permeabilities of THO and the lipid-insoluble molecules became close to the ratio between the corresponding free diffusion coefficients in water. During exposure to EDTA the content of K+ and Na+ of the rete tissue (mostly endothelial cells) became very similar to that of plasma. Similar effects were obtained when the rete was perfused with plasma having a pH below 4 or above 9. The EDTA-effect was reversible during its initial stage. Perfusions with plasma in which Ca and Mg had been removed by dialysis at pH 3.5 were performed. When an EDTA-effect had been induced with this type of perfusates, it could be reversed by addition of equimolar amounts of either Ca++ or Mg++. This indicates Ca++ and Mg++ to be equally important in order to assure normal permeability properties of the capillary membrane."}
{"id": "PMID:241207", "title": "Cardiovascular responses to changes in carotid sinus transmural pressure in man.", "content": "To study the relative importance of cardiac and peripheral effector mechanisms in the carotid sinus baro-reflex in man cardiovascular responses to equal changes of the carotid sinus transmural pressure (Ptm) in either direction of the normal were recorded and compared in eight physically well-trained young male volunteers. In both the supine and the 70 degrees head-up position, a decrease in Ptm produced a more potent reflex response of the systemic arterial pressure than did a similar increase in Ptm. Whereas the arterial pressure response to increased Ptm was due solely to a reduction in vascular resistance, a significant increase in cardiac output contributed to the more potent pressor response to a decrease in Ptm and thus to the predominantly antihypotensive properties that characterize the carotid sinus baroreceptor control system in man. However, since combined beta-adrenergic and parasympathetic blockade abolished the effect of reduced Ptm on cardiac output without greatly impairing the blood pressure response, it is concluded that adjustments in cardiac output are not of critical importance in the buffering function of the carotid sinus baroreceptors. Autonomic cardiac blockade exaggerated the fall in cardiac output on head-up tilt, the arterial pressure remaining unaffected due to a compensatory increase in systemic vascular resistance.", "contents": "Cardiovascular responses to changes in carotid sinus transmural pressure in man. To study the relative importance of cardiac and peripheral effector mechanisms in the carotid sinus baro-reflex in man cardiovascular responses to equal changes of the carotid sinus transmural pressure (Ptm) in either direction of the normal were recorded and compared in eight physically well-trained young male volunteers. In both the supine and the 70 degrees head-up position, a decrease in Ptm produced a more potent reflex response of the systemic arterial pressure than did a similar increase in Ptm. Whereas the arterial pressure response to increased Ptm was due solely to a reduction in vascular resistance, a significant increase in cardiac output contributed to the more potent pressor response to a decrease in Ptm and thus to the predominantly antihypotensive properties that characterize the carotid sinus baroreceptor control system in man. However, since combined beta-adrenergic and parasympathetic blockade abolished the effect of reduced Ptm on cardiac output without greatly impairing the blood pressure response, it is concluded that adjustments in cardiac output are not of critical importance in the buffering function of the carotid sinus baroreceptors. Autonomic cardiac blockade exaggerated the fall in cardiac output on head-up tilt, the arterial pressure remaining unaffected due to a compensatory increase in systemic vascular resistance."}
{"id": "PMID:241208", "title": "Stimulation of adrenergic nerve fibres to the urinary bladder of the rat.", "content": "The contraction of the rat detrusor muscle caused by electrical stimulation of the hypogastric or pelvic nerves was followed by relaxation when the nerves were stimulated for a short period. The relaxation was more pronounced when the initial contraction was reduced by atropine. It was found to be mediated by adrenergic fibres acting on inhibitory beta2-receptors. Stimulation of the hypogastric or pelvic nerves at high frequencies increased the contractile response probably via adrenergic fibres activating excitatory alpha-receptors.", "contents": "Stimulation of adrenergic nerve fibres to the urinary bladder of the rat. The contraction of the rat detrusor muscle caused by electrical stimulation of the hypogastric or pelvic nerves was followed by relaxation when the nerves were stimulated for a short period. The relaxation was more pronounced when the initial contraction was reduced by atropine. It was found to be mediated by adrenergic fibres acting on inhibitory beta2-receptors. Stimulation of the hypogastric or pelvic nerves at high frequencies increased the contractile response probably via adrenergic fibres activating excitatory alpha-receptors."}
{"id": "PMID:241209", "title": "Potentiation by prostaglandins e1, e2, and f2alpha of the contraction response to transmural stimulation in the bovine iris sphincter muscle.", "content": "The contraction response to transmural stimulation in the bovine iris sphincter muscle was abolished by atropine but was left virtually unchanged by hexamethonium, and by adrenergic neuron and receptor blockers, indicating activation of postganglionic cholinergic nerve fibres. Low doses of prostaglandins e1, e2 and F2alpha (0.1-5.3 ng/ml) consistently and apparently in a dose-dependent manner enhanced the contraction response to transmural stimulation. Prostaglandins E1 and E2 were equipotent while F2alpha was at least 10 times less active. Within the same dose range the prostaglandins also enhanced the contraction response to exogenous acetylcholine, indicating that part of the enhancing effect of the prostaglandins on neuromuscular transmission was due to a postjunctional action. A spontaneous increase in tone of the preparation commonly occurred about 1 h after the beginning of the experiment. SC 19220, a potent antagonist of prostaglandin action, reduced the tone and the contraction responses as well as the enhancing effect of the prostaglandins. It is concluded that prostaglandins might serve the function of controlling neuroeffector transmission and muscular tone in the sphincter muscle of the bovine iris.", "contents": "Potentiation by prostaglandins e1, e2, and f2alpha of the contraction response to transmural stimulation in the bovine iris sphincter muscle. The contraction response to transmural stimulation in the bovine iris sphincter muscle was abolished by atropine but was left virtually unchanged by hexamethonium, and by adrenergic neuron and receptor blockers, indicating activation of postganglionic cholinergic nerve fibres. Low doses of prostaglandins e1, e2 and F2alpha (0.1-5.3 ng/ml) consistently and apparently in a dose-dependent manner enhanced the contraction response to transmural stimulation. Prostaglandins E1 and E2 were equipotent while F2alpha was at least 10 times less active. Within the same dose range the prostaglandins also enhanced the contraction response to exogenous acetylcholine, indicating that part of the enhancing effect of the prostaglandins on neuromuscular transmission was due to a postjunctional action. A spontaneous increase in tone of the preparation commonly occurred about 1 h after the beginning of the experiment. SC 19220, a potent antagonist of prostaglandin action, reduced the tone and the contraction responses as well as the enhancing effect of the prostaglandins. It is concluded that prostaglandins might serve the function of controlling neuroeffector transmission and muscular tone in the sphincter muscle of the bovine iris."}
{"id": "PMID:241210", "title": "Influence of amino acids, thiourea and hydroquinone on cellulolytic activity in some Fusarium strains.", "content": "Studies were carried out on the influence of various amino acids: cysteine, cystine, methionine, alanine, serine, tryptophan, and of thiourea and hydroquinone on the activity of cellulase synthesized by four strains of Fusarium. It follows from the results obtained that the addition of amino acids, thiourea or hydroquinone to the culture media stimulates or inhibits the activity of the enzyme studied. The effect of this action depended both on the compound and the strain studied.", "contents": "Influence of amino acids, thiourea and hydroquinone on cellulolytic activity in some Fusarium strains. Studies were carried out on the influence of various amino acids: cysteine, cystine, methionine, alanine, serine, tryptophan, and of thiourea and hydroquinone on the activity of cellulase synthesized by four strains of Fusarium. It follows from the results obtained that the addition of amino acids, thiourea or hydroquinone to the culture media stimulates or inhibits the activity of the enzyme studied. The effect of this action depended both on the compound and the strain studied."}
{"id": "PMID:241211", "title": "The influence of glucose on simazine decomposition.", "content": "Glucose added to soil and to the culture medium of Penicillium citrinum stimulated simazine decomposition. Differences in the rate of simazine decomposition depended on the dose of glucose. Both in soil and in the medium the rate of simazine decomposition was connected with the intensity of development of microorganisms.", "contents": "The influence of glucose on simazine decomposition. Glucose added to soil and to the culture medium of Penicillium citrinum stimulated simazine decomposition. Differences in the rate of simazine decomposition depended on the dose of glucose. Both in soil and in the medium the rate of simazine decomposition was connected with the intensity of development of microorganisms."}
{"id": "PMID:241212", "title": "Effect of the concentration of available carbon compounds on the microbial reduction of sulphates.", "content": "A change of the concentration of available carbon compounds in the reaction medium affecting the carbon to sulphur ratio (C/S) affects the reduction degree of sulphates. The time interval between the initial and the log phase of the process (to) also varies depending on the concentration of carbon compounds. It was demonstrated that optimal reduction conditions for the strain Desulfovibrio desulphuricans used exist in media of C/S = 1.84 +/- 0.2. Kinetic data for the reduction process are presented.", "contents": "Effect of the concentration of available carbon compounds on the microbial reduction of sulphates. A change of the concentration of available carbon compounds in the reaction medium affecting the carbon to sulphur ratio (C/S) affects the reduction degree of sulphates. The time interval between the initial and the log phase of the process (to) also varies depending on the concentration of carbon compounds. It was demonstrated that optimal reduction conditions for the strain Desulfovibrio desulphuricans used exist in media of C/S = 1.84 +/- 0.2. Kinetic data for the reduction process are presented."}
{"id": "PMID:241214", "title": "Effect of chronic alcohol consumption on ethanol and acetaldehyde metabolism.", "content": "Hepatic metabolism of ethanol to acetaldehyde by the alcohol dehydrogenase (ADH) pathway is associated with the generation of reducing equivalents as NADH. Conversely, reducing equivalents are consumed when ethanol oxidation is catalyzed by the NADPH dependent microsomal ethanol oxidizing system (MEOS). Since the major fraction of ethanol metabolism proceeds via ADH and since the oxidation of acetaldehyde also generates NADH, an excess of reducing equivalents is produced. This explains a variety of effects following acute ethanol administration, including hyperlactacidemia, hyperuricemia, enhanced lipogenesis and depressed lipid oxidation. To the extent that ethanol is oxidized by the alternate MEOS pathway, it slows the metabolism of other microsomal substrates. Following chronic ethanol consumption, adaptive microsomal changes prevail, which include enhanced ethanol and drug metabolism, and increased lipoprotein production. Eventually, injury develops with alterations of the rough endoplasmic reticulum and structural and functional abnormalities of the mitochondria.", "contents": "Effect of chronic alcohol consumption on ethanol and acetaldehyde metabolism. Hepatic metabolism of ethanol to acetaldehyde by the alcohol dehydrogenase (ADH) pathway is associated with the generation of reducing equivalents as NADH. Conversely, reducing equivalents are consumed when ethanol oxidation is catalyzed by the NADPH dependent microsomal ethanol oxidizing system (MEOS). Since the major fraction of ethanol metabolism proceeds via ADH and since the oxidation of acetaldehyde also generates NADH, an excess of reducing equivalents is produced. This explains a variety of effects following acute ethanol administration, including hyperlactacidemia, hyperuricemia, enhanced lipogenesis and depressed lipid oxidation. To the extent that ethanol is oxidized by the alternate MEOS pathway, it slows the metabolism of other microsomal substrates. Following chronic ethanol consumption, adaptive microsomal changes prevail, which include enhanced ethanol and drug metabolism, and increased lipoprotein production. Eventually, injury develops with alterations of the rough endoplasmic reticulum and structural and functional abnormalities of the mitochondria."}
{"id": "PMID:241218", "title": "Phosphopyridoxal complexes with histamine and histidine. (2) The influence of presumed complex on histidine decarboxylase activity in rat gastric mucosa.", "content": "It was found that in vitro, histidine and histamine form a complex compound with pyridoxal-5'-phosphate (PLP). The purpose of the present experiments was to find whether formation of this complex can influence histidine decarboxylase activity. It was found that excess PLP inhibits rat's gastric mucosa histidine decarboxylase activity in vitro. The inhibitory action of PLP depends on the histidine concentration and is independent on the amount of crude enzyme preparation. The histidine-PLP complex did not influence enzyme activity. The possible mechanisms of the inhibitory action of PLP on histidine decarboxylase activity are discussed.", "contents": "Phosphopyridoxal complexes with histamine and histidine. (2) The influence of presumed complex on histidine decarboxylase activity in rat gastric mucosa. It was found that in vitro, histidine and histamine form a complex compound with pyridoxal-5'-phosphate (PLP). The purpose of the present experiments was to find whether formation of this complex can influence histidine decarboxylase activity. It was found that excess PLP inhibits rat's gastric mucosa histidine decarboxylase activity in vitro. The inhibitory action of PLP depends on the histidine concentration and is independent on the amount of crude enzyme preparation. The histidine-PLP complex did not influence enzyme activity. The possible mechanisms of the inhibitory action of PLP on histidine decarboxylase activity are discussed."}
{"id": "PMID:241219", "title": "Phosphopyridoxal complexes with histamine and histidine. (3) The influence of presumed complex on activity of rat intestinal histaminase.", "content": "Histamine in high concentration inhibits the rat intestinal histaminase (diamine oxidase E.C. 1.4.3.6.). The apparent Km is approximately 4.2 X 10(-5) M. This inhibition can be reversed by an addition of PLP. It was also found that excess of PLP inhibits enzyme activity. It is competitive inhibition. Histamine and other amines which were associated with enzyme inhibition form spectrophotometricaly demonstrable complex with PLP. The possible mechanism of the inhibitory action of PLP and complex with histamine and other amines on rat intestinal histaminase activity are discussed.", "contents": "Phosphopyridoxal complexes with histamine and histidine. (3) The influence of presumed complex on activity of rat intestinal histaminase. Histamine in high concentration inhibits the rat intestinal histaminase (diamine oxidase E.C. 1.4.3.6.). The apparent Km is approximately 4.2 X 10(-5) M. This inhibition can be reversed by an addition of PLP. It was also found that excess of PLP inhibits enzyme activity. It is competitive inhibition. Histamine and other amines which were associated with enzyme inhibition form spectrophotometricaly demonstrable complex with PLP. The possible mechanism of the inhibitory action of PLP and complex with histamine and other amines on rat intestinal histaminase activity are discussed."}
{"id": "PMID:241223", "title": "Purification and separation of enveloped and unenveloped herpes simplex virus particles.", "content": "Enveloped and unenveloped forms of herpes simplex virus (HSV) occurring in infected rabbit lung (ZP line) cells were purified by differential and discontinuous Ficoll density gradient centrifugation. Then the viral particles were separated in a sucrose-D2O density gradient. In the course of the procedures, both virus preparations were freed of Mg2+-dependent Na+ plus K+-stimulated adenosine triphosphatase (ATPase), 5'-nucleotidase, and glucose-6-phosphatase activities. However, Mg2+ -activated ATPase was shown to be firmly associated with purified virions. The recovery of infectious virus was 50-60 percent. The specific infectivities (TCID50/mg protein) of the purified enveloped and unenveloped viral particles were 1-2 times 10(10) and 2-5 times 10(6), respectively. The infectivity of the unenveloped viral particles was discussed.", "contents": "Purification and separation of enveloped and unenveloped herpes simplex virus particles. Enveloped and unenveloped forms of herpes simplex virus (HSV) occurring in infected rabbit lung (ZP line) cells were purified by differential and discontinuous Ficoll density gradient centrifugation. Then the viral particles were separated in a sucrose-D2O density gradient. In the course of the procedures, both virus preparations were freed of Mg2+-dependent Na+ plus K+-stimulated adenosine triphosphatase (ATPase), 5'-nucleotidase, and glucose-6-phosphatase activities. However, Mg2+ -activated ATPase was shown to be firmly associated with purified virions. The recovery of infectious virus was 50-60 percent. The specific infectivities (TCID50/mg protein) of the purified enveloped and unenveloped viral particles were 1-2 times 10(10) and 2-5 times 10(6), respectively. The infectivity of the unenveloped viral particles was discussed."}
{"id": "PMID:241224", "title": "Heterogeneity of A/Singapore/1/57 (H2N2) influenza virus.", "content": "The population of A/Singapore/1/57 (H2N2) influenza virus was found to contain two types of infectious particle. \"Normal\" virions with a diameter from 100-130 nm, a buoyant density in sucrose of 1.21 g/cm3 and a sedimentation coefficient 770 S represented about 90 percent of the population. In addition, a considerable amount of larger particles (up to 1000 nm) with a buoyant density in sucrose of 1.18 g/cm3 and a sedimentation coefficient of over 1000 S were present.", "contents": "Heterogeneity of A/Singapore/1/57 (H2N2) influenza virus. The population of A/Singapore/1/57 (H2N2) influenza virus was found to contain two types of infectious particle. \"Normal\" virions with a diameter from 100-130 nm, a buoyant density in sucrose of 1.21 g/cm3 and a sedimentation coefficient 770 S represented about 90 percent of the population. In addition, a considerable amount of larger particles (up to 1000 nm) with a buoyant density in sucrose of 1.18 g/cm3 and a sedimentation coefficient of over 1000 S were present."}
{"id": "PMID:241225", "title": "Reproduction in unadapted and adapted cells at 40 degrees C of herpes simplex virus type 1 and type 2 strains.", "content": "Differences in the reproduction of infectious virus in unadapted and adapted rabbit lung cells at 40 degrees C were observed among 8 strains of herpes simplex virus (HSV) type 1 and 6 strains of HSV type 2. The adapted cells represented a permissive system for some strains of both types at supraoptimal temperature. Reproduction of HSV type 2 was not demonstrated in unadapted cells at 40 degrees C. Strains of HSV type 1 reproduced to different titres in unadapted cells grown at 40 degrees C.", "contents": "Reproduction in unadapted and adapted cells at 40 degrees C of herpes simplex virus type 1 and type 2 strains. Differences in the reproduction of infectious virus in unadapted and adapted rabbit lung cells at 40 degrees C were observed among 8 strains of herpes simplex virus (HSV) type 1 and 6 strains of HSV type 2. The adapted cells represented a permissive system for some strains of both types at supraoptimal temperature. Reproduction of HSV type 2 was not demonstrated in unadapted cells at 40 degrees C. Strains of HSV type 1 reproduced to different titres in unadapted cells grown at 40 degrees C."}
{"id": "PMID:241226", "title": "Marek's disease virus (Kekava strain) replication in chickens, chick embryos and cell cultures.", "content": "In the course of 12 passages of Marek's disease virus (MDV) strain Kekava (MDV-Kekava) in chickens, the morbidity varied greatly (from 23 to 50 percent). MDV-Kekava produced plaques in cultures of chick embryo kidney and adult chicken kidney cells and chick embryo fibroblasts (CEF). The virus adaptation to the cultures was very slow. MDV-Kekava induced the formation of pocks on the chorioallantoic membranes (CAM) of chick embryos but the proportion of embryos with CAM lesions did not exceed 24 percent. Serial passaging of the virus in chick embryos beyond the 5th passage was unsuccessful. The results of virus isolation in chickens, cell cultures and chick embryos indicate the possibility of a long-term latent virus carrier state in chickens without development of tumours.", "contents": "Marek's disease virus (Kekava strain) replication in chickens, chick embryos and cell cultures. In the course of 12 passages of Marek's disease virus (MDV) strain Kekava (MDV-Kekava) in chickens, the morbidity varied greatly (from 23 to 50 percent). MDV-Kekava produced plaques in cultures of chick embryo kidney and adult chicken kidney cells and chick embryo fibroblasts (CEF). The virus adaptation to the cultures was very slow. MDV-Kekava induced the formation of pocks on the chorioallantoic membranes (CAM) of chick embryos but the proportion of embryos with CAM lesions did not exceed 24 percent. Serial passaging of the virus in chick embryos beyond the 5th passage was unsuccessful. The results of virus isolation in chickens, cell cultures and chick embryos indicate the possibility of a long-term latent virus carrier state in chickens without development of tumours."}
{"id": "PMID:241227", "title": "The mutagenic effect of measles virus on cell cultures of different origin.", "content": "Differences between strains of measles virus in their mutagenic effect on cells of different animals and man were found. The mutagenic activity of measles virus strains was species-specific. In the process of spontaneous transformation the sensitivity of cells to the mutagen changed.", "contents": "The mutagenic effect of measles virus on cell cultures of different origin. Differences between strains of measles virus in their mutagenic effect on cells of different animals and man were found. The mutagenic activity of measles virus strains was species-specific. In the process of spontaneous transformation the sensitivity of cells to the mutagen changed."}
{"id": "PMID:241228", "title": "Morphological differences in the central nervous system and organs of monkeys inoculated intracerebrally with virulent and attenuated strains of mumps virus.", "content": "The degree of attenuation of mumps virus was studied in intracerebrally inoculated Macaca mulatta monkeys. The virulent Leningrad-3 strain and its attenuated variant as well as the attenuated Sophia-6 strain were used. The nature of pathological alterations in the neurons pointed to neurotropism of only the virulent strain. Morphological changes caused by attenuated and virulent strains in the brain structures, in the epithelium and glandular structures of the salivary glands differed considerably and may be used as a kind of markers of neurovirulence and the degree of attenuation of mumps virus strains.", "contents": "Morphological differences in the central nervous system and organs of monkeys inoculated intracerebrally with virulent and attenuated strains of mumps virus. The degree of attenuation of mumps virus was studied in intracerebrally inoculated Macaca mulatta monkeys. The virulent Leningrad-3 strain and its attenuated variant as well as the attenuated Sophia-6 strain were used. The nature of pathological alterations in the neurons pointed to neurotropism of only the virulent strain. Morphological changes caused by attenuated and virulent strains in the brain structures, in the epithelium and glandular structures of the salivary glands differed considerably and may be used as a kind of markers of neurovirulence and the degree of attenuation of mumps virus strains."}
{"id": "PMID:241229", "title": "Streptovirudins -- new antibiotics with antiviral activity. The antiviral spectrum and inhibition of Newcastle disease virus in cell cultures.", "content": "Streptovirudins are new antibiotics isolated as a mixture of several structurally related compounds from fermentations of Streptomyces griseoflavus (Krainsky) Waksman et Henrici var. thuringensis JA 10124. They possess antiviral activity against RNA and DNA viruses cultivated in chick embryo cells, namely Sindbis, fowl plague, Newcastle disease (NDV), pseudorabies, vaccinia and sheep abortion viruses. The naturally formed streptovirudin complex, in concentrations of 20-2.5 mug/ml inhibited the viral cytopathic effect and caused 100 percent plaque reduction. Mengo, Coxsackie B1-B5, ECHO 30 and 33, and polio (wild and attenuated types 1, 2, and 3) viruses grown in FL cells were not sensitive in the agar-diffusion plaque-inhibition test. The antibiotics failed to show a direct virucidal effect on the NDV virion itself or to influence virus adsorption and penetration processes. Addition of streptovirudin complex during a one-step growth cycle of NDV from 0-4 hours after virus adsorption resulted in complete suppression of virus yield. The antibiotic complex consists of two main groups: I - A1, B1, C1, D1, E1 and II - A2, B2, C2, D2, E2, each of which possess antiviral activity.", "contents": "Streptovirudins -- new antibiotics with antiviral activity. The antiviral spectrum and inhibition of Newcastle disease virus in cell cultures. Streptovirudins are new antibiotics isolated as a mixture of several structurally related compounds from fermentations of Streptomyces griseoflavus (Krainsky) Waksman et Henrici var. thuringensis JA 10124. They possess antiviral activity against RNA and DNA viruses cultivated in chick embryo cells, namely Sindbis, fowl plague, Newcastle disease (NDV), pseudorabies, vaccinia and sheep abortion viruses. The naturally formed streptovirudin complex, in concentrations of 20-2.5 mug/ml inhibited the viral cytopathic effect and caused 100 percent plaque reduction. Mengo, Coxsackie B1-B5, ECHO 30 and 33, and polio (wild and attenuated types 1, 2, and 3) viruses grown in FL cells were not sensitive in the agar-diffusion plaque-inhibition test. The antibiotics failed to show a direct virucidal effect on the NDV virion itself or to influence virus adsorption and penetration processes. Addition of streptovirudin complex during a one-step growth cycle of NDV from 0-4 hours after virus adsorption resulted in complete suppression of virus yield. The antibiotic complex consists of two main groups: I - A1, B1, C1, D1, E1 and II - A2, B2, C2, D2, E2, each of which possess antiviral activity."}
{"id": "PMID:241230", "title": "Selection for plaque variants of two California group arboviruses (Jamestown canyon and La Crosse) by passage in natural vertebrate hosts.", "content": "The plaque size and distribution of prototype La Crosse (LAC) and Jamestown Canyon (JC) viruses were investigated in Vero cell cultures. The effect of serial passage of the viruses in their natural vertebrate hosts - the chipmunk and grey squirrel for LAC and the white-tailed deer for JC virus - was studied. Prototype JC virus was predominately a pinpoint plaque type (about 0.3 mm in diameter). A large plaque variant (about 1.0 mm in diameter), which was only 1 percent of prototype JC virus, increased to over 80 percent of the resultant virus after one passage in white-tailed deer. The large plaque type (about 1.0 mm in diameter) also predominated in JC isolates from mosquitoes, biting flies, and a white-tailed deer in Wisconsin. Prototype LAC virus consisted of a variety of plaque sizes, ranging in diameter from 0.3 mm to 3.0 mm. Passage through chipmunks increased the mean plaque diameter almost twofold, whereas passage in the grey squirrel resulted in a more uniform small plaque population practically eliminating the largest plaques. Preliminary results suggest that the resultant viruses are antigenically different. If these selective processes occur in nature, they man explain how four serologically related California group arboviruses with distinct vector-host cycles in nature could have evolved and have sympatric distribution.", "contents": "Selection for plaque variants of two California group arboviruses (Jamestown canyon and La Crosse) by passage in natural vertebrate hosts. The plaque size and distribution of prototype La Crosse (LAC) and Jamestown Canyon (JC) viruses were investigated in Vero cell cultures. The effect of serial passage of the viruses in their natural vertebrate hosts - the chipmunk and grey squirrel for LAC and the white-tailed deer for JC virus - was studied. Prototype JC virus was predominately a pinpoint plaque type (about 0.3 mm in diameter). A large plaque variant (about 1.0 mm in diameter), which was only 1 percent of prototype JC virus, increased to over 80 percent of the resultant virus after one passage in white-tailed deer. The large plaque type (about 1.0 mm in diameter) also predominated in JC isolates from mosquitoes, biting flies, and a white-tailed deer in Wisconsin. Prototype LAC virus consisted of a variety of plaque sizes, ranging in diameter from 0.3 mm to 3.0 mm. Passage through chipmunks increased the mean plaque diameter almost twofold, whereas passage in the grey squirrel resulted in a more uniform small plaque population practically eliminating the largest plaques. Preliminary results suggest that the resultant viruses are antigenically different. If these selective processes occur in nature, they man explain how four serologically related California group arboviruses with distinct vector-host cycles in nature could have evolved and have sympatric distribution."}
{"id": "PMID:241231", "title": "Growth of Tahyna virus at low temperatures.", "content": "Replication of two Tahyna virus strains in the Aedes albopictus mosquito cell line was studied in the temperature range from 6 to 28 degrees C. The virus grew in this temperature range; its replication rate was related to the temperature of incubation. At lower temperatures the virus titres increased more slowly and did not reach as high maximum values as at higher temperatures. Short increase in incubation temperature resulted in a short increase in the titre of virus previously incubated at 10 degrees C, but not of virus previously incubated at 15 degrees C. At 10 and 15 degrees C, the released virus was demonstrated for more than 300 days past infection (p.i.).", "contents": "Growth of Tahyna virus at low temperatures. Replication of two Tahyna virus strains in the Aedes albopictus mosquito cell line was studied in the temperature range from 6 to 28 degrees C. The virus grew in this temperature range; its replication rate was related to the temperature of incubation. At lower temperatures the virus titres increased more slowly and did not reach as high maximum values as at higher temperatures. Short increase in incubation temperature resulted in a short increase in the titre of virus previously incubated at 10 degrees C, but not of virus previously incubated at 15 degrees C. At 10 and 15 degrees C, the released virus was demonstrated for more than 300 days past infection (p.i.)."}
{"id": "PMID:241232", "title": "Influence of early passages on the character of freshly isolated strains of Tahyna virus.", "content": "The plaque size, thermostability, virulence, and average lethal time of uncloned freshly isolated strains of Tahyna virus were studied in the course of 3 passages in suckling mice. All of the 10 strains were in the 1st passage thermostable (indices 4 degrees/50 degrees C less than 1.0 log10) and highly virulent (indices ic/sc less than 1.0 log10). They differed significantly in plaque size only. The effect of 3 passages in suckling mice was manifested by titre increase and plaque size reduction. The differences in thermostability and virulence were too small as to be distinctly significant, but at least they indicated the heterogeneity of the strains. The variability in behaviour of uncloned strains and significance of changes observed during passages are discussed.", "contents": "Influence of early passages on the character of freshly isolated strains of Tahyna virus. The plaque size, thermostability, virulence, and average lethal time of uncloned freshly isolated strains of Tahyna virus were studied in the course of 3 passages in suckling mice. All of the 10 strains were in the 1st passage thermostable (indices 4 degrees/50 degrees C less than 1.0 log10) and highly virulent (indices ic/sc less than 1.0 log10). They differed significantly in plaque size only. The effect of 3 passages in suckling mice was manifested by titre increase and plaque size reduction. The differences in thermostability and virulence were too small as to be distinctly significant, but at least they indicated the heterogeneity of the strains. The variability in behaviour of uncloned strains and significance of changes observed during passages are discussed."}
{"id": "PMID:241233", "title": "Experiences with the adaptation of crimean hemorrhagic fever virus to the CV-1 monkey cell line.", "content": "Of several cell lines tested, the CV-1 monkey cell line proved to be the most suitable system for propagation of Crimean hemorrhagic fever (CHF) virus. Two CHF strains could be adapted to this cell line by serial passaging. The viral progeny from these passages was specifically cytocidal and produced plaques in CV-1 cells, which could be used in serological diagnosis of CHF. After adaptation of CHF virus to CV-1 cells, the rate of virus synthesis was more rapid, but the yield of virus produced by these cells did not substantially increase. Data reported on cultivation of CHF-Congo viruses are discussed in comparison with the present findings.", "contents": "Experiences with the adaptation of crimean hemorrhagic fever virus to the CV-1 monkey cell line. Of several cell lines tested, the CV-1 monkey cell line proved to be the most suitable system for propagation of Crimean hemorrhagic fever (CHF) virus. Two CHF strains could be adapted to this cell line by serial passaging. The viral progeny from these passages was specifically cytocidal and produced plaques in CV-1 cells, which could be used in serological diagnosis of CHF. After adaptation of CHF virus to CV-1 cells, the rate of virus synthesis was more rapid, but the yield of virus produced by these cells did not substantially increase. Data reported on cultivation of CHF-Congo viruses are discussed in comparison with the present findings."}
{"id": "PMID:241234", "title": "Virus neutralizing antibodies to arboviruses in birds of the order Anseriformes in Czechoslovakia.", "content": "Sera from birds of the order Anseriformes in Czechoslovakia were examined for virus neutralizing (VN) antibodies to arboviruses. VN antibodies to Sindbis, Calovo and Tahyna viruses were found in 15, 5 and 6 out of 106 greylag goose (Anser anser) sera. Out of 38 ducks, 6 mallards (Anas platyrhynchos) and 1 garganey (Anas querquedula) contained VN antibodies to Sindbis virus, 6 mallards to Calovo virus, 4 mallards and 1 garganey to Tahyna virus, 2 mallards and 1 garganey to tick-borne encephalitis (TE) virus and 1 mallard to West Nile (WN) virus.", "contents": "Virus neutralizing antibodies to arboviruses in birds of the order Anseriformes in Czechoslovakia. Sera from birds of the order Anseriformes in Czechoslovakia were examined for virus neutralizing (VN) antibodies to arboviruses. VN antibodies to Sindbis, Calovo and Tahyna viruses were found in 15, 5 and 6 out of 106 greylag goose (Anser anser) sera. Out of 38 ducks, 6 mallards (Anas platyrhynchos) and 1 garganey (Anas querquedula) contained VN antibodies to Sindbis virus, 6 mallards to Calovo virus, 4 mallards and 1 garganey to Tahyna virus, 2 mallards and 1 garganey to tick-borne encephalitis (TE) virus and 1 mallard to West Nile (WN) virus."}
{"id": "PMID:241235", "title": "Development of sensitive methods for detection of latent Kilham virus infection of rats.", "content": "The developed system of procedures, including preliminary selection of rats according to the presence of 19 S antibody in the blood serum, and the use of the most sensitive methods has increased considerably the incidence of detection of Kilham virus (KV) in organs of latently infected rats. To isolate and establish KV strains from the organs of rats in which the specific antigen was detected by immunofluorescence, at least 5-9 passages in rat embryo cell cultures or in newborn Syrian hamsters were required.", "contents": "Development of sensitive methods for detection of latent Kilham virus infection of rats. The developed system of procedures, including preliminary selection of rats according to the presence of 19 S antibody in the blood serum, and the use of the most sensitive methods has increased considerably the incidence of detection of Kilham virus (KV) in organs of latently infected rats. To isolate and establish KV strains from the organs of rats in which the specific antigen was detected by immunofluorescence, at least 5-9 passages in rat embryo cell cultures or in newborn Syrian hamsters were required."}
{"id": "PMID:241236", "title": "Phase II to phase I conversion of Coxiella burneti in immunosuppressed mice.", "content": "Coxiella burneti strains 48 and Nine Mile, serologically in phase II, changed their antigenic properties and virulence for guinea pigs and mice upon passaging in immunosuppressed mice. Conversion to phase I of these strains in a system lacking antibody response throws doubt on the importance of specific antibodies in phase variation of C. burneti.", "contents": "Phase II to phase I conversion of Coxiella burneti in immunosuppressed mice. Coxiella burneti strains 48 and Nine Mile, serologically in phase II, changed their antigenic properties and virulence for guinea pigs and mice upon passaging in immunosuppressed mice. Conversion to phase I of these strains in a system lacking antibody response throws doubt on the importance of specific antibodies in phase variation of C. burneti."}
{"id": "PMID:241237", "title": "Morphological methods of Kilham virus detection.", "content": "Morphological investigations on organs from Kilham virus (KV)-infected Syrian hamsters revealed acute glomerulonephritis with a clear-cut haemorrhagic syndrome. No pathological changes were found in internal organs from KV-infected rats.", "contents": "Morphological methods of Kilham virus detection. Morphological investigations on organs from Kilham virus (KV)-infected Syrian hamsters revealed acute glomerulonephritis with a clear-cut haemorrhagic syndrome. No pathological changes were found in internal organs from KV-infected rats."}
{"id": "PMID:241239", "title": "Electron microscopic demonstration of Crimean hemorrhagic fever virus in CV-1 cells.", "content": "Crimean hemorrhagic fever (CHF) virus was detected by electron microscopy in ultrathin sections of CV-1 cells. The virus particles appeared spherical or oval and occurred both intra- and extracellularly. Based on their size and density of their contents, two types of virions, probably representing different phases of the reproduction cycle of CHF virus, could be distinguished.", "contents": "Electron microscopic demonstration of Crimean hemorrhagic fever virus in CV-1 cells. Crimean hemorrhagic fever (CHF) virus was detected by electron microscopy in ultrathin sections of CV-1 cells. The virus particles appeared spherical or oval and occurred both intra- and extracellularly. Based on their size and density of their contents, two types of virions, probably representing different phases of the reproduction cycle of CHF virus, could be distinguished."}
{"id": "PMID:241240", "title": "Characteristics of Sendai virus RNA transcriptive complex formed in the cytoplasm of infected ascites cells.", "content": "Virus-specific structures with sedimentation coefficients of 250-300, 200 and 150 S were isolated from the polysome fraction of Sendai virus-infected Ahrlich ascitic carcinoma cells treated with cycloheximide, at early stages of infection (1.5 to 2 hours after inoculation). All these 3 types of structure contained both parental and newly synthesized viral RNA. RNA extracted from these structures consisted of 2 components sedimenting in sucrose density gradients in the zones of 50-70 and 35-40 S. Both components contained parental and newly synthesized RNA and were partially resistant to ribonuclease. RNA extracted from rapidly sedimenting structures (250-300 S) contained mainly the 50-70 S component; RNA recovered from 200 S structures contained the 35-40 S component. By analogy with reported data, the isolated forms of RNA have been characterized as transcriptive intermediates.", "contents": "Characteristics of Sendai virus RNA transcriptive complex formed in the cytoplasm of infected ascites cells. Virus-specific structures with sedimentation coefficients of 250-300, 200 and 150 S were isolated from the polysome fraction of Sendai virus-infected Ahrlich ascitic carcinoma cells treated with cycloheximide, at early stages of infection (1.5 to 2 hours after inoculation). All these 3 types of structure contained both parental and newly synthesized viral RNA. RNA extracted from these structures consisted of 2 components sedimenting in sucrose density gradients in the zones of 50-70 and 35-40 S. Both components contained parental and newly synthesized RNA and were partially resistant to ribonuclease. RNA extracted from rapidly sedimenting structures (250-300 S) contained mainly the 50-70 S component; RNA recovered from 200 S structures contained the 35-40 S component. By analogy with reported data, the isolated forms of RNA have been characterized as transcriptive intermediates."}
{"id": "PMID:241241", "title": "Purification of togavirus haemagglutinins by chromatography on controlled pore glass.", "content": "Purified preparations of haemagglutinins from Sindbis, West Nile and tick-borne encephalitis (TBE) viruses could be obtained from infected mouse brains by alkaline extraction, precipitation with protamine and chromatography on polyethylene glycol-coated controlled pore glass with 242 A pore diameter.", "contents": "Purification of togavirus haemagglutinins by chromatography on controlled pore glass. Purified preparations of haemagglutinins from Sindbis, West Nile and tick-borne encephalitis (TBE) viruses could be obtained from infected mouse brains by alkaline extraction, precipitation with protamine and chromatography on polyethylene glycol-coated controlled pore glass with 242 A pore diameter."}
{"id": "PMID:241242", "title": "The effect of temperature and urea on virulent and attenuated strains of pseudoabies virus.", "content": "Out of 10 virulent strains of pseudorabies virus (PRV), 9 proved to be resistant and 3 out of 4 attenuated strains were sensitive to the temperature of 53 degrees C. No differences were found between attenuated and virulent strains of PRV in their rate of inactivation of 2 M urea; its inactivating effect was enhanced by increasing the temperature. The t (effect of temperature) and u (effect of urea) markers proved unsuitable for a sufficient characterization of PRV strains.", "contents": "The effect of temperature and urea on virulent and attenuated strains of pseudoabies virus. Out of 10 virulent strains of pseudorabies virus (PRV), 9 proved to be resistant and 3 out of 4 attenuated strains were sensitive to the temperature of 53 degrees C. No differences were found between attenuated and virulent strains of PRV in their rate of inactivation of 2 M urea; its inactivating effect was enhanced by increasing the temperature. The t (effect of temperature) and u (effect of urea) markers proved unsuitable for a sufficient characterization of PRV strains."}
{"id": "PMID:241243", "title": "Physico-chemical characteristics of interferons induced by human adenovirus in chick fibroblasts and leucocytes.", "content": "The physico-chemical characteristics of interferons with different anti-viral activities produced in chick fibroblast cells and leucocytes in response to the human adenovirus type 12 were investigated. The molecular weights of interferons produced by chick fibroblasts and leucocytes were similar: the main anti-viral activity was found at 27000 and 32000 and a low-titered shoulder at 28000 and 23000 respectively. Under our experimental conditions no oligomeric structure of interferons could be detected. The isoelectric pattern of leucocyte interferon was slightly different from that of the fibroblast interferon.", "contents": "Physico-chemical characteristics of interferons induced by human adenovirus in chick fibroblasts and leucocytes. The physico-chemical characteristics of interferons with different anti-viral activities produced in chick fibroblast cells and leucocytes in response to the human adenovirus type 12 were investigated. The molecular weights of interferons produced by chick fibroblasts and leucocytes were similar: the main anti-viral activity was found at 27000 and 32000 and a low-titered shoulder at 28000 and 23000 respectively. Under our experimental conditions no oligomeric structure of interferons could be detected. The isoelectric pattern of leucocyte interferon was slightly different from that of the fibroblast interferon."}
{"id": "PMID:241244", "title": "Herpesvirus-induced availability of host DNA to exogenous endonuclease.", "content": "Deoxyribonuclease I penetrates herpesvirus-infected L cells and degrades host DNA without interfering with viral multiplication. The DNA of uninfected control monolayers of L cells, disrupted by scraping, is similarly attacked. In contrast, undisturbed L cells are not affected. This suggests that altered cell membrane permeability allows the nuclease to enter the cell, thereby permitting access of exogenous deoxyribonuclease to cellular DNA.", "contents": "Herpesvirus-induced availability of host DNA to exogenous endonuclease. Deoxyribonuclease I penetrates herpesvirus-infected L cells and degrades host DNA without interfering with viral multiplication. The DNA of uninfected control monolayers of L cells, disrupted by scraping, is similarly attacked. In contrast, undisturbed L cells are not affected. This suggests that altered cell membrane permeability allows the nuclease to enter the cell, thereby permitting access of exogenous deoxyribonuclease to cellular DNA."}
{"id": "PMID:241245", "title": "Polymorphism of human blood groups and incidence of influenza A/Hong Kong (H3N2).", "content": "During three epidemics of influenza A/Hong Kong (H3N2) and experimentally in vaccines, the relation between influenza infection and ABo, Rh and MN blood groups was studied. Examinations of 2760 patients with laboratory-confirmed diagnosis of influenza and 749 persons vaccinated with live influenza vaccine showed that individuals of blood groups O and B were susceptible to influenza 1.67 and 1.20 times more, respectively, than individuals of blood group A. The difference in incidence was most manifested in first attacks and decreased in subsequent epidemics. The increased incidence in individuals of blood groups O and B as compared to those of blood group A was not associated with factors of specific (antibody) and nonspecific (interferon) resistance to influenza but was related to a greater capacity of leukocytes from these individuals to adsorb the virus. No relation between blood groups Ph and MN and incidence of influenza A/Hong Kong (H3N2) was established.", "contents": "Polymorphism of human blood groups and incidence of influenza A/Hong Kong (H3N2). During three epidemics of influenza A/Hong Kong (H3N2) and experimentally in vaccines, the relation between influenza infection and ABo, Rh and MN blood groups was studied. Examinations of 2760 patients with laboratory-confirmed diagnosis of influenza and 749 persons vaccinated with live influenza vaccine showed that individuals of blood groups O and B were susceptible to influenza 1.67 and 1.20 times more, respectively, than individuals of blood group A. The difference in incidence was most manifested in first attacks and decreased in subsequent epidemics. The increased incidence in individuals of blood groups O and B as compared to those of blood group A was not associated with factors of specific (antibody) and nonspecific (interferon) resistance to influenza but was related to a greater capacity of leukocytes from these individuals to adsorb the virus. No relation between blood groups Ph and MN and incidence of influenza A/Hong Kong (H3N2) was established."}
{"id": "PMID:241246", "title": "Diagnosis of rhinovirus-infections by virological and immunofluorescent methods.", "content": "In January--May, 1971, detection of rhinoviurs infections among ambulatory patients with respiratory diseases in Moscow was carried out in parallel by virological and immunofluorescent methods. Rhinovirus infections were virologically confirmed in 13% out of 238 patients. By the indirect immunofluorescence technique, rhinovirus antigens of serotype 17 were detected in 2.2% out of 220 patients, of type 1B in 4.3% out of 183 patients, of type 48 in 5.6% out of 123 patients and of type 7 in 4.6% out of 86 patients. The use of immunofluorescence supplemented the results of virological examinations and increase the effectiveness of aetiological diagnosis of rhinovirus infections.", "contents": "Diagnosis of rhinovirus-infections by virological and immunofluorescent methods. In January--May, 1971, detection of rhinoviurs infections among ambulatory patients with respiratory diseases in Moscow was carried out in parallel by virological and immunofluorescent methods. Rhinovirus infections were virologically confirmed in 13% out of 238 patients. By the indirect immunofluorescence technique, rhinovirus antigens of serotype 17 were detected in 2.2% out of 220 patients, of type 1B in 4.3% out of 183 patients, of type 48 in 5.6% out of 123 patients and of type 7 in 4.6% out of 86 patients. The use of immunofluorescence supplemented the results of virological examinations and increase the effectiveness of aetiological diagnosis of rhinovirus infections."}
{"id": "PMID:241247", "title": "Phagocytosis of Coxiella burneti by macrophages.", "content": "Live or killed purified phase I and phase II Coxiella burneti organisms were phagocytized to a similar extent by mouse or guinea pig peritoneal macrophages and polymorphonuclear leukocytes (PMN); phase II was much more susceptible to phagocytosis than phase I. Phagocytosis of phase I was enhanced only by immune sera containing phase I antibodies. Increased in vivo phagocytosis of phase I organisms by macrophages from animals immunized with live phase I C. burneti was lost following their in vitro cultivation and washing.", "contents": "Phagocytosis of Coxiella burneti by macrophages. Live or killed purified phase I and phase II Coxiella burneti organisms were phagocytized to a similar extent by mouse or guinea pig peritoneal macrophages and polymorphonuclear leukocytes (PMN); phase II was much more susceptible to phagocytosis than phase I. Phagocytosis of phase I was enhanced only by immune sera containing phase I antibodies. Increased in vivo phagocytosis of phase I organisms by macrophages from animals immunized with live phase I C. burneti was lost following their in vitro cultivation and washing."}
{"id": "PMID:241248", "title": "Use of duck embryo cell cultures for the study of arbovirus reproduction.", "content": "Duck embryo cell (DEC) cultures were used for the study of arbovirus reproduction. High sensitivity of DEC cultures to Japanese encephalitis, West Nile, Tyuleniy, Sakhalin and Baku viruses was established. DEC cultures are recommended for investigation of arbovirus reproduction.", "contents": "Use of duck embryo cell cultures for the study of arbovirus reproduction. Duck embryo cell (DEC) cultures were used for the study of arbovirus reproduction. High sensitivity of DEC cultures to Japanese encephalitis, West Nile, Tyuleniy, Sakhalin and Baku viruses was established. DEC cultures are recommended for investigation of arbovirus reproduction."}
{"id": "PMID:241250", "title": "Some properties of clover blotch virus.", "content": "Clover blotch virus (CBV) was purified by differential centrifugation or precipitation with polyethylene glycol 6000 or 20000. Analytical centrifugation of purified CBV preparations revealed 2 components, the proportions of the lighter (96 S) nad heavier (112 S) being 88 and 12%, respectively. RNA isolated from purified CBV represented a micture of several RNA species of different molecular weight and its infectivity was by about 2 log units lower than that of the original nucleoprotein. CBV virions are isometric with a diameter of 28 nm. CBV is tentatively included into the Cucumovirus group.", "contents": "Some properties of clover blotch virus. Clover blotch virus (CBV) was purified by differential centrifugation or precipitation with polyethylene glycol 6000 or 20000. Analytical centrifugation of purified CBV preparations revealed 2 components, the proportions of the lighter (96 S) nad heavier (112 S) being 88 and 12%, respectively. RNA isolated from purified CBV represented a micture of several RNA species of different molecular weight and its infectivity was by about 2 log units lower than that of the original nucleoprotein. CBV virions are isometric with a diameter of 28 nm. CBV is tentatively included into the Cucumovirus group."}
{"id": "PMID:241251", "title": "Isolation of spotted fever group and Wolbachia-like agents from field-collected materials by means of plaque formation in mammalian and mosquito cells.", "content": "Three isolations from ticks (Dermacentor occidentalis) of a rickettsia of the spotted fever group and 5 isolations from chipmunk (Eutamias rugicaudus) blood of a Wolbachia-like agent were obtained from plaques formed in Singh's Aedes albopictus (mosquito) and Vero (African green monkey kidney) cell cultures. These organisms could not be isolated by injection of the infected ticks or blood into embryonated chicken eggs, guinea pigs, or voles (Microtus pennsylvanicus), but fluid cultures of Grace's Antheraea eucalypti (moth1 and Singh's A. albopictus cells inoculated with the bloods yielded the Wolbachia-like agent.", "contents": "Isolation of spotted fever group and Wolbachia-like agents from field-collected materials by means of plaque formation in mammalian and mosquito cells. Three isolations from ticks (Dermacentor occidentalis) of a rickettsia of the spotted fever group and 5 isolations from chipmunk (Eutamias rugicaudus) blood of a Wolbachia-like agent were obtained from plaques formed in Singh's Aedes albopictus (mosquito) and Vero (African green monkey kidney) cell cultures. These organisms could not be isolated by injection of the infected ticks or blood into embryonated chicken eggs, guinea pigs, or voles (Microtus pennsylvanicus), but fluid cultures of Grace's Antheraea eucalypti (moth1 and Singh's A. albopictus cells inoculated with the bloods yielded the Wolbachia-like agent."}
{"id": "PMID:241254", "title": "A rapid method for the determination of fluoride in vegetation.", "content": "An analytical procedure for the determination of fluroide in vegetation has been developed to aid in environmental studies. The method involves leaching the vegetation with a hot solution of strong base and then determining the fluoride in an acidified solution directly with a fluoride selective ion electrode.", "contents": "A rapid method for the determination of fluoride in vegetation. An analytical procedure for the determination of fluroide in vegetation has been developed to aid in environmental studies. The method involves leaching the vegetation with a hot solution of strong base and then determining the fluoride in an acidified solution directly with a fluoride selective ion electrode."}
{"id": "PMID:241255", "title": "Removal of cyanoacrylate vapor from work spaces by activated carbon.", "content": "The purpose of this research program was to evaluate several gas sorbents for methyl-2-cyanoacrylate vapor collection efficiency and service life in portable, recirculating room air filters. Two acid carbons were found to be effective and are recommended for further evaluation under actual field conditions.", "contents": "Removal of cyanoacrylate vapor from work spaces by activated carbon. The purpose of this research program was to evaluate several gas sorbents for methyl-2-cyanoacrylate vapor collection efficiency and service life in portable, recirculating room air filters. Two acid carbons were found to be effective and are recommended for further evaluation under actual field conditions."}
{"id": "PMID:241257", "title": "Thin layer chromatographic identification of phenothiazines in urine specimens.", "content": "Two newly developed, thin layer chromatographic (TLC) solvent systems are presented to separate and identify commonly used phenothiazines in the presence of other drugs in urine specimens. These solvent systems are 1) ethyl acetate: n-butanol: concentrated ammonium hydroxide (89:10:1.5) and 2) ethyl acetate: O-dichlorobenzene: concentrated ammonium hydroxide (90:9:1.4). The phenothiazines are identified on the TLC plates both by Rf values and by colors produced with ethanolic sulfuric acid and palladium chloride sprays. With this method 0.025 mug/ml levels of unchanged phenothiazines can be detected in urine specimens.", "contents": "Thin layer chromatographic identification of phenothiazines in urine specimens. Two newly developed, thin layer chromatographic (TLC) solvent systems are presented to separate and identify commonly used phenothiazines in the presence of other drugs in urine specimens. These solvent systems are 1) ethyl acetate: n-butanol: concentrated ammonium hydroxide (89:10:1.5) and 2) ethyl acetate: O-dichlorobenzene: concentrated ammonium hydroxide (90:9:1.4). The phenothiazines are identified on the TLC plates both by Rf values and by colors produced with ethanolic sulfuric acid and palladium chloride sprays. With this method 0.025 mug/ml levels of unchanged phenothiazines can be detected in urine specimens."}
{"id": "PMID:241258", "title": "The effect of increased maternal PaO2 upon the fetus during labor.", "content": "The effect of increased maternal PaO2 upon the fetus during labor was studied in 36 subhuman primates. The animals were divided into two groups, one in which the fetus was not asphyxiated and showed no evidence of fetal distress (Group I) and another in which the fetus was acidotic, hypoxic, and exhibited the pattern of late deceleration of the heart rate (Group II). One hundred per cent oxygen was administered to the mothers for a period of 30 minutes. Elevation of maternal PaO2 to 430 mm. Hg increased fetal oxygen levels in Group I. and in most instances in Group II, without significant changes in the acid-base state. In Group II, maternal hyperoxemia also abolished or reduced the frequency of late deceleration of the fetal heart in most animals but had little or no effect on fetal blood pressure. Termination of high-concentration oxygen to the mother resulted in a fall in maternal and fetal oxygen levels to their original values and the reappearance of late fetal heart decelerations. Thus, administration of high-concentration oxygen to the mother for the treatment of fetal distress may be of some benefit. The problems of fetal acidosis and hypotension are not cured, however, and may still progress if there is placental insufficiency or cord compression. Therefore, this treatment should be regarded as a temporary supportive measure only.", "contents": "The effect of increased maternal PaO2 upon the fetus during labor. The effect of increased maternal PaO2 upon the fetus during labor was studied in 36 subhuman primates. The animals were divided into two groups, one in which the fetus was not asphyxiated and showed no evidence of fetal distress (Group I) and another in which the fetus was acidotic, hypoxic, and exhibited the pattern of late deceleration of the heart rate (Group II). One hundred per cent oxygen was administered to the mothers for a period of 30 minutes. Elevation of maternal PaO2 to 430 mm. Hg increased fetal oxygen levels in Group I. and in most instances in Group II, without significant changes in the acid-base state. In Group II, maternal hyperoxemia also abolished or reduced the frequency of late deceleration of the fetal heart in most animals but had little or no effect on fetal blood pressure. Termination of high-concentration oxygen to the mother resulted in a fall in maternal and fetal oxygen levels to their original values and the reappearance of late fetal heart decelerations. Thus, administration of high-concentration oxygen to the mother for the treatment of fetal distress may be of some benefit. The problems of fetal acidosis and hypotension are not cured, however, and may still progress if there is placental insufficiency or cord compression. Therefore, this treatment should be regarded as a temporary supportive measure only."}
{"id": "PMID:241259", "title": "Pharmacologic control of uterine contractility. In vitro human and in vivo monkey studies.", "content": "The exact cause and mechanism of the onset of labor are unknown but the theories are many. There is considerable evidence that prostaglandins are potent stimulants of uterine activity and may play a role in the onset of labor. Prostaglandin release may be the natural mediator of uterine contractions during labor. A group of anti-inflammatory compounds (aspirin-like compounds) that inhibit prostaglandin synthesis include indomethacin and fenoprofen. Inhibition of prostaglandin production is a reasonable approach to inhibiting premature labor. An excised muscle strip technique was used as a screening procedure for pharmacologic depression of human uterine activity in vitro, testing isoxsuprine, mesuprine, Alupent, ritodrine, indomethacin, and fenoprofen. The prostaglandin antagonists indomethacin and fenoprofen exhibited marked depressant activity. These drugs were further tested in an in vivo rhesus monkey preparation measuring uterine activity, maternal blood pressure, uterine blood flow, fetal heart rate, fetal blood pressure, and blood gases. Fenoprofen is effective in reducing uterine contractility without serious maternal or fetal side effects and shows promise as a clinically effective agent for pharmacologic control of premature labor.", "contents": "Pharmacologic control of uterine contractility. In vitro human and in vivo monkey studies. The exact cause and mechanism of the onset of labor are unknown but the theories are many. There is considerable evidence that prostaglandins are potent stimulants of uterine activity and may play a role in the onset of labor. Prostaglandin release may be the natural mediator of uterine contractions during labor. A group of anti-inflammatory compounds (aspirin-like compounds) that inhibit prostaglandin synthesis include indomethacin and fenoprofen. Inhibition of prostaglandin production is a reasonable approach to inhibiting premature labor. An excised muscle strip technique was used as a screening procedure for pharmacologic depression of human uterine activity in vitro, testing isoxsuprine, mesuprine, Alupent, ritodrine, indomethacin, and fenoprofen. The prostaglandin antagonists indomethacin and fenoprofen exhibited marked depressant activity. These drugs were further tested in an in vivo rhesus monkey preparation measuring uterine activity, maternal blood pressure, uterine blood flow, fetal heart rate, fetal blood pressure, and blood gases. Fenoprofen is effective in reducing uterine contractility without serious maternal or fetal side effects and shows promise as a clinically effective agent for pharmacologic control of premature labor."}
{"id": "PMID:241260", "title": "Secondary ocular bacterial infection in hypovitaminosis a xerophthalmia.", "content": "Extraocular bacterial culture was performed in 100 patients with hypovitaminosis A xerophthalmia. There was corneal ulceration in 29 cases and corneal perforation in 22 cases. Eighty-six percent of the patients harbored frankly pathogenic bacteria (46 patients) and potentially pathogenic bacteria (40 patients). All but two patients with either cornal ulceration or perforation harbored potentially pathogenic or frankly pathogenic bacteria. Pseudomonas aeruginosa, Diplococcus pneumoniae, and Moraxella species were isolated in 37% (19 patients) of cases with corneal ulceration and perforation. I cultured P. aeruginosa from 36% (eight patients) of cases with corneal perforation. The many ocular secondary bacterial infections in the early stages of xerophthalmia seem to suggest that bacterial action plays a major role in causing the corneal ulceration and perforation in hypovitaminosis A xerophthalmia.", "contents": "Secondary ocular bacterial infection in hypovitaminosis a xerophthalmia. Extraocular bacterial culture was performed in 100 patients with hypovitaminosis A xerophthalmia. There was corneal ulceration in 29 cases and corneal perforation in 22 cases. Eighty-six percent of the patients harbored frankly pathogenic bacteria (46 patients) and potentially pathogenic bacteria (40 patients). All but two patients with either cornal ulceration or perforation harbored potentially pathogenic or frankly pathogenic bacteria. Pseudomonas aeruginosa, Diplococcus pneumoniae, and Moraxella species were isolated in 37% (19 patients) of cases with corneal ulceration and perforation. I cultured P. aeruginosa from 36% (eight patients) of cases with corneal perforation. The many ocular secondary bacterial infections in the early stages of xerophthalmia seem to suggest that bacterial action plays a major role in causing the corneal ulceration and perforation in hypovitaminosis A xerophthalmia."}
{"id": "PMID:241261", "title": "Hepatotoxicity of vinyl chloride and 1,1-dichloroethylene. Role of mixed function oxidase system.", "content": "Vinyl chloride, an occupational carcinogen, produces acute liver injury in rats pretreated with phenobarbital or Aroclor 1254. Injury appears related to morphologic changes in the endoplasmic reticulum. The degree of injury, as indicated by elevation of serum enzymes derived from the liver, correlates with the magnitude of induction of cytochrome P-450 and its reduction by NADPH. Hepatic injury following 1,1-dichloroethylene exposure differs strikingly from that caused by vinyl chloride and appears to involve plasma membranes, mitochondria, and chromatin and spares endoplasmic reticulum. Induction of cytochrome P-450 appears to protect against 1,1-dichloroethylene but not vinyl chloride.", "contents": "Hepatotoxicity of vinyl chloride and 1,1-dichloroethylene. Role of mixed function oxidase system. Vinyl chloride, an occupational carcinogen, produces acute liver injury in rats pretreated with phenobarbital or Aroclor 1254. Injury appears related to morphologic changes in the endoplasmic reticulum. The degree of injury, as indicated by elevation of serum enzymes derived from the liver, correlates with the magnitude of induction of cytochrome P-450 and its reduction by NADPH. Hepatic injury following 1,1-dichloroethylene exposure differs strikingly from that caused by vinyl chloride and appears to involve plasma membranes, mitochondria, and chromatin and spares endoplasmic reticulum. Induction of cytochrome P-450 appears to protect against 1,1-dichloroethylene but not vinyl chloride."}
{"id": "PMID:241263", "title": "[Blood-pressure regulating drugs and intraocular pressure in animal experiments (author's transl)].", "content": "Electromanometric measurements of blood pressure and intraocular pressure, carried out in rabbits after the intravenous administration of Norphen, Peripherin, Sympatol, Hydergin, Tropodil, Complamin, Euphyllin and Vasculat showed that the changes in the pressure curves were largely in the same sense. Apart from a \"passive\" correlation of the intraocular pressure with the blood pressure, the local effects of pharmaceuticals administered are also discussed. The results obtained provide both general medicine and ophthalmology with insights into the mode of action of drugs, some of which are frequently administered. In addition, they serve both to provide information on the desirable curative effects of the drugs and to help prevent damage being done to the organ of sight.", "contents": "[Blood-pressure regulating drugs and intraocular pressure in animal experiments (author's transl)]. Electromanometric measurements of blood pressure and intraocular pressure, carried out in rabbits after the intravenous administration of Norphen, Peripherin, Sympatol, Hydergin, Tropodil, Complamin, Euphyllin and Vasculat showed that the changes in the pressure curves were largely in the same sense. Apart from a \"passive\" correlation of the intraocular pressure with the blood pressure, the local effects of pharmaceuticals administered are also discussed. The results obtained provide both general medicine and ophthalmology with insights into the mode of action of drugs, some of which are frequently administered. In addition, they serve both to provide information on the desirable curative effects of the drugs and to help prevent damage being done to the organ of sight."}
{"id": "PMID:241264", "title": "Hyperventilation in neurosurgery.", "content": "An outline of the nature and varieties of hyperventilation is presented together with a discussion on the role of artificial hyperventilation in the management of neurosurgical patients. Attention is called to the value of gasometric investigations in the ventricular cerebrospinal fluid for evaluation of disturbances in pH of the intracranial environment and possible effectiveness of hyperventilation. The results of our measurements of cerebrospinal fluid pressure are presented in 21 cases of supratentorial cerebral tumours in which controlled ventilation with hyperventilation was conducted. In 19 cases, the cerebrospinal fluid pressure fell by a mean of 44.3% with a simultaneous fall of PaCO2 by 29.3%. In the conclusions the authors stress the role of hyperventilation in the lowering of raised cerebrospinal fluid pressure and prevention of cerebral oedema.", "contents": "Hyperventilation in neurosurgery. An outline of the nature and varieties of hyperventilation is presented together with a discussion on the role of artificial hyperventilation in the management of neurosurgical patients. Attention is called to the value of gasometric investigations in the ventricular cerebrospinal fluid for evaluation of disturbances in pH of the intracranial environment and possible effectiveness of hyperventilation. The results of our measurements of cerebrospinal fluid pressure are presented in 21 cases of supratentorial cerebral tumours in which controlled ventilation with hyperventilation was conducted. In 19 cases, the cerebrospinal fluid pressure fell by a mean of 44.3% with a simultaneous fall of PaCO2 by 29.3%. In the conclusions the authors stress the role of hyperventilation in the lowering of raised cerebrospinal fluid pressure and prevention of cerebral oedema."}
{"id": "PMID:241267", "title": "Reversal of lorazepam delirium by physostigmine.", "content": "Two adult patients suffered postoperative delirium following administration of lorazepam, a new benzodiazepine sedative. Physostigmine was found effective in reversing all untoward central nervous system effects.", "contents": "Reversal of lorazepam delirium by physostigmine. Two adult patients suffered postoperative delirium following administration of lorazepam, a new benzodiazepine sedative. Physostigmine was found effective in reversing all untoward central nervous system effects."}
{"id": "PMID:241271", "title": "[Cardiovascular effects of Rohypnol used as an agent to induce anesthesia].", "content": "The study involved 34 surgical patients in whom anaesthesia was induced by the intravenous injection of an average dose of 2.5 mg of flunitrazepam (Rohypnol or Ro-5-4200). The induction of anaesthetic sleep was obtained in 50 to 60 seconds and the duration of the anaesthetic effect 15 to 20 minutes. The patients continued to show hypnosedative effects for several hours postoperatively. The cardiovascular parameters studied - radial BP, ECG and pulmonary arterial pressure - were recorded directly whilst cardiac output was measured by thermodilution using a Swan-Ganz catheter. The decrease in systolic and diastolic pressures in relation to pre-anaesthetic values was 21 p. 100 and 16 p. 100 respectively, whilst pulmonary artery pressure fell by 13 p. 100. Cardiac output fell in a non-significant fashion and the same applied to systolic ejection volume for a given constant heart rate. There was a significant (18 p. 100) decrease in total peripheral resistance but alterations in central venous pressure were negligeable. The decrease in peripheral vascular and pulmonary artery resistances suggest that the product has a peripheral circulatory action and it is possible to correct the alterations seen.", "contents": "[Cardiovascular effects of Rohypnol used as an agent to induce anesthesia]. The study involved 34 surgical patients in whom anaesthesia was induced by the intravenous injection of an average dose of 2.5 mg of flunitrazepam (Rohypnol or Ro-5-4200). The induction of anaesthetic sleep was obtained in 50 to 60 seconds and the duration of the anaesthetic effect 15 to 20 minutes. The patients continued to show hypnosedative effects for several hours postoperatively. The cardiovascular parameters studied - radial BP, ECG and pulmonary arterial pressure - were recorded directly whilst cardiac output was measured by thermodilution using a Swan-Ganz catheter. The decrease in systolic and diastolic pressures in relation to pre-anaesthetic values was 21 p. 100 and 16 p. 100 respectively, whilst pulmonary artery pressure fell by 13 p. 100. Cardiac output fell in a non-significant fashion and the same applied to systolic ejection volume for a given constant heart rate. There was a significant (18 p. 100) decrease in total peripheral resistance but alterations in central venous pressure were negligeable. The decrease in peripheral vascular and pulmonary artery resistances suggest that the product has a peripheral circulatory action and it is possible to correct the alterations seen."}
{"id": "PMID:241272", "title": "[Comparative study of post-anesthesia awakening and behavior following alfatesine and pentothal].", "content": "A study of behaviour during the awakening of subjects which had been anaesthetized with a single dose of Alfatesine or of Pentothal was undertaken. This comparison between two anaesthetic drugs offers the opportunity to make, firstly, a critical analysis of the methods of exploration of anaesthetic awakening which are habitually used. An attempt at the definition of this period and a review of the literature on the subject are given, as well as the possible approaches to this period, insisting principally on psychomotor tests. A list of variables which enter into consideration in this type of study completes the account of the methodology. Next, the procedure for the experimental study properly speaking is given. Seven psychomotor tests were chosen, completed by a clinical study. The timetable, the anaesthetic conditions and the process of collecting the information are explained. The clinical results and the results obtained from the tests show extensive perturbations of behaviour lasting for up to one-and-a-half hours following the injection of one or the other product. However, the intensity and the duration of the disturbances recorded are definitely greater with Pentothal. In addition, the state of anxiety before operation could be shown objectively through certain tests. A study of this type poses a certain number of problems and perspectives which are envisaged.", "contents": "[Comparative study of post-anesthesia awakening and behavior following alfatesine and pentothal]. A study of behaviour during the awakening of subjects which had been anaesthetized with a single dose of Alfatesine or of Pentothal was undertaken. This comparison between two anaesthetic drugs offers the opportunity to make, firstly, a critical analysis of the methods of exploration of anaesthetic awakening which are habitually used. An attempt at the definition of this period and a review of the literature on the subject are given, as well as the possible approaches to this period, insisting principally on psychomotor tests. A list of variables which enter into consideration in this type of study completes the account of the methodology. Next, the procedure for the experimental study properly speaking is given. Seven psychomotor tests were chosen, completed by a clinical study. The timetable, the anaesthetic conditions and the process of collecting the information are explained. The clinical results and the results obtained from the tests show extensive perturbations of behaviour lasting for up to one-and-a-half hours following the injection of one or the other product. However, the intensity and the duration of the disturbances recorded are definitely greater with Pentothal. In addition, the state of anxiety before operation could be shown objectively through certain tests. A study of this type poses a certain number of problems and perspectives which are envisaged."}
{"id": "PMID:241273", "title": "[Intrathoracic gas effusions of iatrogenic origin in neonatal reanimation].", "content": "Intra-thoracic gaseous collections, pneumodiastinum and pneumothorax, have become more common since the use of positive expiratory pressure, either with spontaneous ventilation or in association with artificial ventilation. In our experience, the occurence rate of such collections has increased from 7 p. 100 in 1970 to 19 p. 100 in 1974, related to the use of continuous positive pressure of long duration in the treatment of idiopathic respiratory distress or hyaline membrane disease. These gaseous collections were initially associated with a high mortality (50 p. 100) which is now practically nil. Improved knowledge of the clinical and radiological signs and the insertion of thoracic drains in the presence of the slightest doubt represent the explanation of this reduced mortality.", "contents": "[Intrathoracic gas effusions of iatrogenic origin in neonatal reanimation]. Intra-thoracic gaseous collections, pneumodiastinum and pneumothorax, have become more common since the use of positive expiratory pressure, either with spontaneous ventilation or in association with artificial ventilation. In our experience, the occurence rate of such collections has increased from 7 p. 100 in 1970 to 19 p. 100 in 1974, related to the use of continuous positive pressure of long duration in the treatment of idiopathic respiratory distress or hyaline membrane disease. These gaseous collections were initially associated with a high mortality (50 p. 100) which is now practically nil. Improved knowledge of the clinical and radiological signs and the insertion of thoracic drains in the presence of the slightest doubt represent the explanation of this reduced mortality."}
{"id": "PMID:241274", "title": "[Perforation of the cervical esophagus during tracheal intubation. Apropos of a personal case].", "content": "On the occasion of a personal case of perforation of the cervical oesophagus by laborious tracheal intubation which had necessitated the use of a rigid stilet, we found seven similar cases in the literature since 1971 which can be added to the 16 collected by DUBOST in 1971. We analyse the etiological circumstances, the clinical picture the course and action taken in these eight cases. From this we draw practical conclusions which are imperative during anesthesia.", "contents": "[Perforation of the cervical esophagus during tracheal intubation. Apropos of a personal case]. On the occasion of a personal case of perforation of the cervical oesophagus by laborious tracheal intubation which had necessitated the use of a rigid stilet, we found seven similar cases in the literature since 1971 which can be added to the 16 collected by DUBOST in 1971. We analyse the etiological circumstances, the clinical picture the course and action taken in these eight cases. From this we draw practical conclusions which are imperative during anesthesia."}
{"id": "PMID:241275", "title": "[Evaluation of 1200 venous catheterizations in reanimation].", "content": "The authors present a series of 1247 venous catheterizations during resuscitation, the latter being carried out under particularly strict aseptic conditions. This series contains especially: - 364 internal jugular catheterizations; - 223 subclavian catheterizations; - 130 femoral catheterizations. The total number of days of infusion is 6300, of which 3,619 were of prolonged parenteral feeding. 79.5 p. 100 of the catheters cultured proved to be sterile; in the case of those cultures which were positive, 6.5 p. 100 were due to pathogenic organisms, 13.9 p. 100 were due to saprophytes. On the whole, 7 septicemies of venous origin (0.56 p. 100 of all of the catheterizations) were observed. The d\u00e9tailed study of each route shows that the frequency of cultures of pathogen positive catheters is practically the same in all cases. On the other hand, the frequency of cultures of catheters positive with saprophytes is evidently higher for the internal jugular vein; this being particularly true in the male where the role of the beard as a contaminating factor is evoked. The importance of asepsis in the procedure of putting venous catheters in place and in their maintenance seems to be welle demonstrated by the results presented.", "contents": "[Evaluation of 1200 venous catheterizations in reanimation]. The authors present a series of 1247 venous catheterizations during resuscitation, the latter being carried out under particularly strict aseptic conditions. This series contains especially: - 364 internal jugular catheterizations; - 223 subclavian catheterizations; - 130 femoral catheterizations. The total number of days of infusion is 6300, of which 3,619 were of prolonged parenteral feeding. 79.5 p. 100 of the catheters cultured proved to be sterile; in the case of those cultures which were positive, 6.5 p. 100 were due to pathogenic organisms, 13.9 p. 100 were due to saprophytes. On the whole, 7 septicemies of venous origin (0.56 p. 100 of all of the catheterizations) were observed. The d\u00e9tailed study of each route shows that the frequency of cultures of pathogen positive catheters is practically the same in all cases. On the other hand, the frequency of cultures of catheters positive with saprophytes is evidently higher for the internal jugular vein; this being particularly true in the male where the role of the beard as a contaminating factor is evoked. The importance of asepsis in the procedure of putting venous catheters in place and in their maintenance seems to be welle demonstrated by the results presented."}
{"id": "PMID:241280", "title": "[Automatic dosage of uric acid by urate oxydase. Comparison with Praetorius' methods].", "content": "The authors describe an automatic method of estimation of uric acid based on the colour obtained in the presence of Gaiac resin and peroxidase, and the hydrogen peroxide produced by the action of urate oxidase on uric acid.", "contents": "[Automatic dosage of uric acid by urate oxydase. Comparison with Praetorius' methods]. The authors describe an automatic method of estimation of uric acid based on the colour obtained in the presence of Gaiac resin and peroxidase, and the hydrogen peroxide produced by the action of urate oxidase on uric acid."}
{"id": "PMID:241276", "title": "[Value of Soludactone in cardiac surgery in adults].", "content": "The use of potassium canrenoate (Soludactone) in the post-operative period in 31 patients who had undergone open-heart surgery, in comparison with a control batch of patients, led to a more rapid and easier regression of myocardial hyperexcitability, the maintenance of kaliemia at values near normal, a reduction in kaliuresis, a rapid elevation of the urinary Na/K ratio and the maintenance of satisfactory diuresis. But the majority of these effects appear progressively during the first 3 days of treatment, so potassium canrenoate should be prescribed 3 days before the intervention so that the beneficial effects may be manifested from the day of the intervention itself.", "contents": "[Value of Soludactone in cardiac surgery in adults]. The use of potassium canrenoate (Soludactone) in the post-operative period in 31 patients who had undergone open-heart surgery, in comparison with a control batch of patients, led to a more rapid and easier regression of myocardial hyperexcitability, the maintenance of kaliemia at values near normal, a reduction in kaliuresis, a rapid elevation of the urinary Na/K ratio and the maintenance of satisfactory diuresis. But the majority of these effects appear progressively during the first 3 days of treatment, so potassium canrenoate should be prescribed 3 days before the intervention so that the beneficial effects may be manifested from the day of the intervention itself."}
{"id": "PMID:241277", "title": "[Auricular adynamia due to hyperkalemia].", "content": "Auricular asystoly (A.A.) was the electrocardiographic pattern of 6 patients admitted for electrolytic disorders secondary to either renal failure or inadequate treatment. A rapid increase of blood potassium was the unique commun abnormality found to explain the dysrhytmia. Bradycardia (between 25 and 55 beats/mn) was present in each case with or without clinical symptoms. Temporary prophylactic pace maker insertion was performed in 4/7 patients. Recovery appeared after dialysis treatment in 6 cases, medical treatment in one, sinus rhythm being present in 6 and chronic atrial fibrillation in one. Prognosis of A.A. due to hyperkaliemia is good when hydroelectrolytic disorders are rapidly corrected. Follow up of blood electrolytes and electrocardiogram must be regular to prevent reccurencies.", "contents": "[Auricular adynamia due to hyperkalemia]. Auricular asystoly (A.A.) was the electrocardiographic pattern of 6 patients admitted for electrolytic disorders secondary to either renal failure or inadequate treatment. A rapid increase of blood potassium was the unique commun abnormality found to explain the dysrhytmia. Bradycardia (between 25 and 55 beats/mn) was present in each case with or without clinical symptoms. Temporary prophylactic pace maker insertion was performed in 4/7 patients. Recovery appeared after dialysis treatment in 6 cases, medical treatment in one, sinus rhythm being present in 6 and chronic atrial fibrillation in one. Prognosis of A.A. due to hyperkaliemia is good when hydroelectrolytic disorders are rapidly corrected. Follow up of blood electrolytes and electrocardiogram must be regular to prevent reccurencies."}
{"id": "PMID:241279", "title": "[Measurement of differences in oxygen between arteries and veins. Application to the study of cerebral metabolism].", "content": "The cerebral metabolic exploration requires a precises measurement of the arterio-venous differences and this, for each metabolite. As far as oxygen is concerned, there are many techniques to measure the blood contents (CaO2 - CvO2). Direct methods give accurate results but their high technicality makes it difficult to adapt them to the increasing medical demand. The authors report the principle and the technique of the indirect method based upon the measurement of the total hemoglobin concentration and the saturation in oxygen. They recall the possible causes of errors, the main of which - induced by an insufficient homogenization of the sample - is (by the way) to be found in both groups of methods although to a lesser degree in the indirect method. Therefore, the latter, that all normally equipped laboratories can carry into practice, seems quite adapted to the \"hospital demand\" and its validity confirmed by an experience that now belongs to the past.", "contents": "[Measurement of differences in oxygen between arteries and veins. Application to the study of cerebral metabolism]. The cerebral metabolic exploration requires a precises measurement of the arterio-venous differences and this, for each metabolite. As far as oxygen is concerned, there are many techniques to measure the blood contents (CaO2 - CvO2). Direct methods give accurate results but their high technicality makes it difficult to adapt them to the increasing medical demand. The authors report the principle and the technique of the indirect method based upon the measurement of the total hemoglobin concentration and the saturation in oxygen. They recall the possible causes of errors, the main of which - induced by an insufficient homogenization of the sample - is (by the way) to be found in both groups of methods although to a lesser degree in the indirect method. Therefore, the latter, that all normally equipped laboratories can carry into practice, seems quite adapted to the \"hospital demand\" and its validity confirmed by an experience that now belongs to the past."}
{"id": "PMID:241283", "title": "The defined antigen substrate spheres (DASS) system and some of its applications.", "content": "A quantitative immunofluorescent technique based on the covalent coupling of protein to Sepharose beads, the so-called defined antigen substrate spheres (DASS) system is described, and the main technical aspects are discussed. The method proved to be reproducible and has a lower detection limit equivalent to the amount of antigen, present per bead, that can bind 1 pg fluorescent labeled antibody. The DASS system has many applications, and some of them are discussed, such as the quantitation of antibodies and antigens with Sepharose-coupled antigens or antibodies. Not only antigen-antibody interactions but also any reaction that results in a stable complex can be studied, provided antisera against one of the constituents are available. An example is given by the complement fixation to Sepharose-coupled IgG. For the quantitation of hydrophobic antigens, hydrophobic Sepharise can be used.", "contents": "The defined antigen substrate spheres (DASS) system and some of its applications. A quantitative immunofluorescent technique based on the covalent coupling of protein to Sepharose beads, the so-called defined antigen substrate spheres (DASS) system is described, and the main technical aspects are discussed. The method proved to be reproducible and has a lower detection limit equivalent to the amount of antigen, present per bead, that can bind 1 pg fluorescent labeled antibody. The DASS system has many applications, and some of them are discussed, such as the quantitation of antibodies and antigens with Sepharose-coupled antigens or antibodies. Not only antigen-antibody interactions but also any reaction that results in a stable complex can be studied, provided antisera against one of the constituents are available. An example is given by the complement fixation to Sepharose-coupled IgG. For the quantitation of hydrophobic antigens, hydrophobic Sepharise can be used."}
{"id": "PMID:241285", "title": "[Possibility of the intrauterine sensitization to benzylpenicillin and ampicillin in Syrian hamsters].", "content": "Immunization of Syrian female hamsters with benzylpenicillin and ampicillin resulted in positive skin reactions of the retarded type and decreased titers of the blood antihistamine factor (AHF) in a part of the posterity. Penicillin allergy was in particular observed in the posterity of the female hamsters immunited before the pregnancy. The state of allergy to penicillins was found in the posterity of the female hamsters with both the positive and negative skin reactions on immunization during the 2nd half of the pregnancy.", "contents": "[Possibility of the intrauterine sensitization to benzylpenicillin and ampicillin in Syrian hamsters]. Immunization of Syrian female hamsters with benzylpenicillin and ampicillin resulted in positive skin reactions of the retarded type and decreased titers of the blood antihistamine factor (AHF) in a part of the posterity. Penicillin allergy was in particular observed in the posterity of the female hamsters immunited before the pregnancy. The state of allergy to penicillins was found in the posterity of the female hamsters with both the positive and negative skin reactions on immunization during the 2nd half of the pregnancy."}
{"id": "PMID:241286", "title": "Biochemical properties of a penicillin beta-lactamase mediated by R factor from Bordetella bronchiseptica.", "content": "The beta-lactamase specified by an R(te16) plasmid in Bordetella bronchiseptica was purified 200-fold by carboxymethyl-Sephadex column chromatography and electrofocusing. The enzyme has a molecular weight of 46,000 +/- 3,000 and an isoelectric point of 8.3 and was highly active against phenethicillin, oxacillin, and propicillin. The enzyme activity was inhibited by sodium chloride but not by ferrous ion. The maximal enzyme activity to benzylpenicillin was observed at pH 7.0 to 7.5 and at 40 C. It is concluded that this enzyme is different from the R-mediated beta-lactamases, i.e., the type I and type II beta-lactamases which have been classified in previous papers.", "contents": "Biochemical properties of a penicillin beta-lactamase mediated by R factor from Bordetella bronchiseptica. The beta-lactamase specified by an R(te16) plasmid in Bordetella bronchiseptica was purified 200-fold by carboxymethyl-Sephadex column chromatography and electrofocusing. The enzyme has a molecular weight of 46,000 +/- 3,000 and an isoelectric point of 8.3 and was highly active against phenethicillin, oxacillin, and propicillin. The enzyme activity was inhibited by sodium chloride but not by ferrous ion. The maximal enzyme activity to benzylpenicillin was observed at pH 7.0 to 7.5 and at 40 C. It is concluded that this enzyme is different from the R-mediated beta-lactamases, i.e., the type I and type II beta-lactamases which have been classified in previous papers."}
{"id": "PMID:241287", "title": "Mecillinam (FL 1060), a 6beta-amidinopenicillanic acid derivative: in vitro evaluation.", "content": "Mecillinam (formerly called FL 1060), a novel 6beta-amidinopenicillanic acid derivative, showed markedly higher activity than ampicillin against clinical isolates of Enterobacteriaceae. The mode of action of mecillinam is different from that of ampicillin and consequently no intrinsic cross-resistance between the two antibiotics was observed. Mecillinam is inactivated by beta-lactamases but is generally more stable than ampicillin; thus an apparent cross-resistance exists for strong beta-lactamase producers. The protein binding was low and the activity was relatively independent of pH between 5.5 and 8.0. Slow-growing, insensitive variants of Escherichia coli could be selected but these were not stable. The frequency of insensitive variants was affected by the sodium chloride concentration in the medium.", "contents": "Mecillinam (FL 1060), a 6beta-amidinopenicillanic acid derivative: in vitro evaluation. Mecillinam (formerly called FL 1060), a novel 6beta-amidinopenicillanic acid derivative, showed markedly higher activity than ampicillin against clinical isolates of Enterobacteriaceae. The mode of action of mecillinam is different from that of ampicillin and consequently no intrinsic cross-resistance between the two antibiotics was observed. Mecillinam is inactivated by beta-lactamases but is generally more stable than ampicillin; thus an apparent cross-resistance exists for strong beta-lactamase producers. The protein binding was low and the activity was relatively independent of pH between 5.5 and 8.0. Slow-growing, insensitive variants of Escherichia coli could be selected but these were not stable. The frequency of insensitive variants was affected by the sodium chloride concentration in the medium."}
{"id": "PMID:241288", "title": "Preparation and properties of a cephalosporin acetylesterase adsorbed onto bentonite.", "content": "A cephalosporin acetylesterase produced by Bacillus subtilis was immobilized by adsorption onto bentonite. The immobilized enzyme (E(I)) and the soluble enzyme (E(S)) exhibited Michaelis-Menton kinetics with 7-aminocephalosporanic acid (7-ACA): K(m) = 2.8 x 10(-3) M and K(m) = 3.2 x 10(-3) M, respectively. Similar kinetics were observed with 7-(thiophene-2-acetamido)cephalosporanic acid (cephalothin), but the K(m) value measured with E(I) (3.7 x 10(-3) M) was less than one-half that measured with this substrate and E(S). The reduction in K(m) value was correlated with the ability of bentonite to adsorb cephalothin. The reaction products, acetate and deacetyl-7-ACA, were weak competitive inhibitors of E(S) and E(I). The K(i) values for E(I) were 5.0 x 10(-2) M for acetate and 3.6 x 10(-2) M for deacetyl-7-ACA. Similar values were measured with E(S) and these substrates. E(I) retained about 80% of its initial activity after 3 weeks of storage in solution at 25 C. However, the enzyme dissociated from the bentonite particles during the deacetylation reaction. This dissociation was minimized by cross-linking E(I) with glutaraldehyde or bis-dimethyladipimidate, or by adding Al(OH)(3) to the suspension. With the latter addition, E(I) was stabilized so that it could be reused nine times before one-half of the initial activity was lost.", "contents": "Preparation and properties of a cephalosporin acetylesterase adsorbed onto bentonite. A cephalosporin acetylesterase produced by Bacillus subtilis was immobilized by adsorption onto bentonite. The immobilized enzyme (E(I)) and the soluble enzyme (E(S)) exhibited Michaelis-Menton kinetics with 7-aminocephalosporanic acid (7-ACA): K(m) = 2.8 x 10(-3) M and K(m) = 3.2 x 10(-3) M, respectively. Similar kinetics were observed with 7-(thiophene-2-acetamido)cephalosporanic acid (cephalothin), but the K(m) value measured with E(I) (3.7 x 10(-3) M) was less than one-half that measured with this substrate and E(S). The reduction in K(m) value was correlated with the ability of bentonite to adsorb cephalothin. The reaction products, acetate and deacetyl-7-ACA, were weak competitive inhibitors of E(S) and E(I). The K(i) values for E(I) were 5.0 x 10(-2) M for acetate and 3.6 x 10(-2) M for deacetyl-7-ACA. Similar values were measured with E(S) and these substrates. E(I) retained about 80% of its initial activity after 3 weeks of storage in solution at 25 C. However, the enzyme dissociated from the bentonite particles during the deacetylation reaction. This dissociation was minimized by cross-linking E(I) with glutaraldehyde or bis-dimethyladipimidate, or by adding Al(OH)(3) to the suspension. With the latter addition, E(I) was stabilized so that it could be reused nine times before one-half of the initial activity was lost."}
{"id": "PMID:241289", "title": "Biosynthesis of mycophenolic acid: purification and characterization of S-adenosyl-L-methionine: demethylmycophenolic acid O-methyltransferase.", "content": "The final step in the biosynthesis of mycophenolic acid involves the transfer of a methyl group from S-adenosylmethionine to demethylmycophenolic acid. The enzyme, S-adenosylmethionine:demethylmycophenolic acid O-methyltransferase, was isolated from Penicillium stoloniferum and purified 2,700-fold by ammonium sulfate fractionation and diethylaminoethyl-cellulose and Sephadex G-200 chromatography. Maximum enzyme activity was achieved at pH 7.5 and a temperature of 27 to 28 C. The apparent K(m) for demethylmycophenolic acid was 3.1 x 10(-6) M. The enzyme preparation was 50% inactivated when exposed to 33 C for 15 min. Mycophenolic acid, homocystine, S-adenosyl-homocysteine, ethanol, and Mg(2+) inhibited the methyltransferase. This enzyme appears to be subject to end product inhibition which may regulate the synthesis of mycophenolic acid. The methyltransferase activity was highest during the early phases of the fermentation.", "contents": "Biosynthesis of mycophenolic acid: purification and characterization of S-adenosyl-L-methionine: demethylmycophenolic acid O-methyltransferase. The final step in the biosynthesis of mycophenolic acid involves the transfer of a methyl group from S-adenosylmethionine to demethylmycophenolic acid. The enzyme, S-adenosylmethionine:demethylmycophenolic acid O-methyltransferase, was isolated from Penicillium stoloniferum and purified 2,700-fold by ammonium sulfate fractionation and diethylaminoethyl-cellulose and Sephadex G-200 chromatography. Maximum enzyme activity was achieved at pH 7.5 and a temperature of 27 to 28 C. The apparent K(m) for demethylmycophenolic acid was 3.1 x 10(-6) M. The enzyme preparation was 50% inactivated when exposed to 33 C for 15 min. Mycophenolic acid, homocystine, S-adenosyl-homocysteine, ethanol, and Mg(2+) inhibited the methyltransferase. This enzyme appears to be subject to end product inhibition which may regulate the synthesis of mycophenolic acid. The methyltransferase activity was highest during the early phases of the fermentation."}
{"id": "PMID:241290", "title": "Metalloprotease from Bacillus thuringiensis.", "content": "Bacillus thuringiensis var. kurstaki was shown to produce an extracellular, metal chelator-sensitive protease during the early stages of sporulation. Protease production in nutrient broth was dependent upon supplementation with Mn2+ or Ca2. The addition of Ca24 was required for enzyme stabilization...", "contents": "Metalloprotease from Bacillus thuringiensis. Bacillus thuringiensis var. kurstaki was shown to produce an extracellular, metal chelator-sensitive protease during the early stages of sporulation. Protease production in nutrient broth was dependent upon supplementation with Mn2+ or Ca2. The addition of Ca24 was required for enzyme stabilization..."}
{"id": "PMID:241291", "title": "Influence of wine composition on the heat resistance of potential spoilage organisms.", "content": "Pasteurization studies were conducted on 29 yeast and five lactic acid bacteria. In general the yeasts were more heat resistant in wine than were the bacteria. The one exception was a strain of Lactobacillus fructivorans that gave an average D-value of 1.7 min at 60 C. Alcohol was the wine constituent that had the greatest effect on resistance; D-values for all test species were inversely related to the ethanol concentration. The response of organisms to other factors such as pH, sugar, and sulfur dioxide varied with the species.", "contents": "Influence of wine composition on the heat resistance of potential spoilage organisms. Pasteurization studies were conducted on 29 yeast and five lactic acid bacteria. In general the yeasts were more heat resistant in wine than were the bacteria. The one exception was a strain of Lactobacillus fructivorans that gave an average D-value of 1.7 min at 60 C. Alcohol was the wine constituent that had the greatest effect on resistance; D-values for all test species were inversely related to the ethanol concentration. The response of organisms to other factors such as pH, sugar, and sulfur dioxide varied with the species."}
{"id": "PMID:241292", "title": "Physical properties and kinetic behavior of a cephalosporin acetylesterase produced by Bacillus subtilis.", "content": "An esterase that deacetylates cephalosporins was recovered from the supernatant of a Bacillus subtilis culture. It was partially purified by ammonium sulfate fractionation and ultrafiltration. The enzyme had a temperature optimum between 40 and 50 C and a pH optimum of 7.0. The molecular weight was estimated by gel filtration to be 190,000. The enzyme was very stable and retained greater than 80% of its activity after storage in solution at 25 C for 1 month. The esterase exhibited Michaelis-Menton kinetics with the substrates 7-aminocephalosporanic acid (7-ACA) and 7-(thiophene-2-acetamido)cephalosporanic acid (cephalothin); the K(m) values were 2.8 X 10(-3) and 8.3 X 10(-3) M, respectively. The products of 7-ACA deacetylation were weak competitive inhibitors, and a K(i) value of 5.0 X 10(-2) M was determined for acetate and of 3.6 X 10-2 M for deacetyl-7-ACA. Weak product inhibition did not prevent the deacetylation reaction from going to completion. A 5-mg/ml solution of partially purified esterase completely hydrolyzed (greater than 99.5%) a 24-mg/ml solution of 7-ACA in 3 h. Because of the kinetic properties and excellent stability, this enzyme may be useful in an immobilized form to prepare large quantities of deacetylated cephalosporin derivatives.", "contents": "Physical properties and kinetic behavior of a cephalosporin acetylesterase produced by Bacillus subtilis. An esterase that deacetylates cephalosporins was recovered from the supernatant of a Bacillus subtilis culture. It was partially purified by ammonium sulfate fractionation and ultrafiltration. The enzyme had a temperature optimum between 40 and 50 C and a pH optimum of 7.0. The molecular weight was estimated by gel filtration to be 190,000. The enzyme was very stable and retained greater than 80% of its activity after storage in solution at 25 C for 1 month. The esterase exhibited Michaelis-Menton kinetics with the substrates 7-aminocephalosporanic acid (7-ACA) and 7-(thiophene-2-acetamido)cephalosporanic acid (cephalothin); the K(m) values were 2.8 X 10(-3) and 8.3 X 10(-3) M, respectively. The products of 7-ACA deacetylation were weak competitive inhibitors, and a K(i) value of 5.0 X 10(-2) M was determined for acetate and of 3.6 X 10-2 M for deacetyl-7-ACA. Weak product inhibition did not prevent the deacetylation reaction from going to completion. A 5-mg/ml solution of partially purified esterase completely hydrolyzed (greater than 99.5%) a 24-mg/ml solution of 7-ACA in 3 h. Because of the kinetic properties and excellent stability, this enzyme may be useful in an immobilized form to prepare large quantities of deacetylated cephalosporin derivatives."}
{"id": "PMID:241301", "title": "Bisulfite induced lipid oxidation.", "content": "Bisulfite (0.5 to 10 millimolar) initiates oxidation of lipids in aqueous emulsions of corn oil in a dose-dependent manner as measured by reaction with thiobarbituric acid. The reaction is effectively quenched by the antioxidant, 2,6-dit-butyl-4-hydroxymethyl phenol as well as by Mn+2 (10(-5)-10(-3)M). The latter observation is in disagreement with that reported by others and suggests that in case of lipids an alternative mechanism exists for the initiation of reactive species.", "contents": "Bisulfite induced lipid oxidation. Bisulfite (0.5 to 10 millimolar) initiates oxidation of lipids in aqueous emulsions of corn oil in a dose-dependent manner as measured by reaction with thiobarbituric acid. The reaction is effectively quenched by the antioxidant, 2,6-dit-butyl-4-hydroxymethyl phenol as well as by Mn+2 (10(-5)-10(-3)M). The latter observation is in disagreement with that reported by others and suggests that in case of lipids an alternative mechanism exists for the initiation of reactive species."}
{"id": "PMID:241302", "title": "Ectopic apudocarcinomas and associated endocrine hyperplasias of the foregut.", "content": "Foregut endocrine polypeptide-secreting APUD cells (Amine-Precursor-Uptake and Decarboxylation), in their embryologic migration from neural crest to foregut may become \"arrested\" in the mesoderm or in other ectopic locations. They may become hyperplastic, adenomatous or malignant. Eight illustrative patients are reported. One patient had \"pancreatic hyperparathyroidism\" with hypercalcemic crises, pancreatic apudocarcinoma, normal parathyroids, biologically active parathormone, but inert immunochemically to the usual parathyroid antisera. Two had gastrin-secreting malignancies in the mesoderm. Remission after excision, but eventual recurrence of the syndrome due to islet cell hyperplasia required total gastrectomy. One patient had a gastric corpus apudocarcinoma found prospectively with hypergastrinemia which required excision of the tumor. One patient had acromegaly with hypergastrinemia and antral gastrinosis treated by pituitary irradiation,  One patient had the antral or intermediary type of the Zollinger-Ellison syndrome with moderate hypergastrinemia, duodenal ulcer and antral gastrinosis, treated by vagotomy and antrectomy. One patient had hyperparathyroidism with antral gastrinosis, treated by parathyroidectomy. One patient had malignant Zollinger-Ellison syndrome and developed associated thyroid parafollicular cell hyperplasia and parathyroid chief cell hyperplasia, treated by total gastrectomy and multiple endocrine excisions. These investigative observations demonstrate ectopic loci and associated hyperplasias which support the concept of migration and bizarre potentiality of polypeptide-secreting cells of the foregut.", "contents": "Ectopic apudocarcinomas and associated endocrine hyperplasias of the foregut. Foregut endocrine polypeptide-secreting APUD cells (Amine-Precursor-Uptake and Decarboxylation), in their embryologic migration from neural crest to foregut may become \"arrested\" in the mesoderm or in other ectopic locations. They may become hyperplastic, adenomatous or malignant. Eight illustrative patients are reported. One patient had \"pancreatic hyperparathyroidism\" with hypercalcemic crises, pancreatic apudocarcinoma, normal parathyroids, biologically active parathormone, but inert immunochemically to the usual parathyroid antisera. Two had gastrin-secreting malignancies in the mesoderm. Remission after excision, but eventual recurrence of the syndrome due to islet cell hyperplasia required total gastrectomy. One patient had a gastric corpus apudocarcinoma found prospectively with hypergastrinemia which required excision of the tumor. One patient had acromegaly with hypergastrinemia and antral gastrinosis treated by pituitary irradiation,  One patient had the antral or intermediary type of the Zollinger-Ellison syndrome with moderate hypergastrinemia, duodenal ulcer and antral gastrinosis, treated by vagotomy and antrectomy. One patient had hyperparathyroidism with antral gastrinosis, treated by parathyroidectomy. One patient had malignant Zollinger-Ellison syndrome and developed associated thyroid parafollicular cell hyperplasia and parathyroid chief cell hyperplasia, treated by total gastrectomy and multiple endocrine excisions. These investigative observations demonstrate ectopic loci and associated hyperplasias which support the concept of migration and bizarre potentiality of polypeptide-secreting cells of the foregut."}
{"id": "PMID:241303", "title": "A study of the effect of d-amphetamine on the toxicity, analgesic potency and swimming impairment caused by potent analgesics in mice.", "content": "The addition of d-amphetamine to morphine has been reported to result in an increase of analgesic potency in experimental animals and man, but no data on the toxicity of such combinations are available. This study is intended to provide systematic information on the toxicity, analgesic potency and degree of physical impairment (swimming endurance) of a combination of 12 mg morphine sulfate with 10 mg d-amphetamine HCl per ml which is now under clinical investigation. Mice were used as experimental subjects. Meperidine, methadone and pentazocine were substituted for morphine using clinically equally analgesic doses and keeping the d-amphetamine amount constant. The toxicity of all analgesics especially that of morphine was enhanced in the combination, least so in the case of meperidine. The degree of increase of analgesic power by the addition of d-amphetamine was greatest with morphine and quantitatively in satisfactory agreement with present clinical experiences. However, the relationship between the increases of toxicity and of analgesia is not necessarily most favorable for this drug. For the other three analgesics increases in toxicity and analgesia were more in line, meperidine showing the best ratio. Swimming endurance was decreased with full analgesic doses of all four compounds. The presence of d-amphetamine tended to reverse this depression. The data were analyzed in relation to their possible predictive value for the use of such combinations in man for the therapeutic dose range and in the event of overdosage.", "contents": "A study of the effect of d-amphetamine on the toxicity, analgesic potency and swimming impairment caused by potent analgesics in mice. The addition of d-amphetamine to morphine has been reported to result in an increase of analgesic potency in experimental animals and man, but no data on the toxicity of such combinations are available. This study is intended to provide systematic information on the toxicity, analgesic potency and degree of physical impairment (swimming endurance) of a combination of 12 mg morphine sulfate with 10 mg d-amphetamine HCl per ml which is now under clinical investigation. Mice were used as experimental subjects. Meperidine, methadone and pentazocine were substituted for morphine using clinically equally analgesic doses and keeping the d-amphetamine amount constant. The toxicity of all analgesics especially that of morphine was enhanced in the combination, least so in the case of meperidine. The degree of increase of analgesic power by the addition of d-amphetamine was greatest with morphine and quantitatively in satisfactory agreement with present clinical experiences. However, the relationship between the increases of toxicity and of analgesia is not necessarily most favorable for this drug. For the other three analgesics increases in toxicity and analgesia were more in line, meperidine showing the best ratio. Swimming endurance was decreased with full analgesic doses of all four compounds. The presence of d-amphetamine tended to reverse this depression. The data were analyzed in relation to their possible predictive value for the use of such combinations in man for the therapeutic dose range and in the event of overdosage."}
{"id": "PMID:241304", "title": "[The calorigenic effect of glucagon].", "content": "The calorigenic action of glucagon was studied in several species by measuring its effect on the oxygen comsumption. The calorigenic effect was most pronounced in the quail and also evident in young adult rats of two different strains but not in mice and guinea pigs. The influence of various drugs on the calorigenic effect of glucagon was investigated in rats. Ganglionic blocking agents (hexamethonium, mecamylamine, chlorisondamine) as well as adrenergic blocking drugs (propranolol, butoxamine, phentolamine) greatly reduced the glucagon-induced calorigenesis but after pretreatment with reserpine, guanethidine or chemical sympathectomy with 6-hydroxydopamine the calorigenic effect of glucagon was exaggerated. It was somewhat diminished by nicotinic acid but not by chlorpromazine or lithium and potentiated by cocaine but not by theophylline.--These results are not indicative for an involvement of adenly cyclase--cyclic AMP--system in glucagon-induced calorigenesis but they are compatible with the assumption that the hormone enhances the metabolic rate by releasing catecholamines from the adrenal medulla.", "contents": "[The calorigenic effect of glucagon]. The calorigenic action of glucagon was studied in several species by measuring its effect on the oxygen comsumption. The calorigenic effect was most pronounced in the quail and also evident in young adult rats of two different strains but not in mice and guinea pigs. The influence of various drugs on the calorigenic effect of glucagon was investigated in rats. Ganglionic blocking agents (hexamethonium, mecamylamine, chlorisondamine) as well as adrenergic blocking drugs (propranolol, butoxamine, phentolamine) greatly reduced the glucagon-induced calorigenesis but after pretreatment with reserpine, guanethidine or chemical sympathectomy with 6-hydroxydopamine the calorigenic effect of glucagon was exaggerated. It was somewhat diminished by nicotinic acid but not by chlorpromazine or lithium and potentiated by cocaine but not by theophylline.--These results are not indicative for an involvement of adenly cyclase--cyclic AMP--system in glucagon-induced calorigenesis but they are compatible with the assumption that the hormone enhances the metabolic rate by releasing catecholamines from the adrenal medulla."}
{"id": "PMID:241306", "title": "Anxiety in schizophrenia. The responses to chlordiazepoxide in an intensive design study.", "content": "Six anxious schizophrenic patients who were maintained with phenothiazines participated in a double-blind intensive design study of chlordiazepoxide and placebo for 12 weeks or longer. There were substantial differences between patients in their responses to chlordiazepoxide: two patients experienced significant and conspicuous relief of distress and reduction of typical schizophrenic symptoms. In another patient the differences, although statistically significant, were clinically less striking. In the three remaining patients no differences were observed between responses to the two treatments except that one patient was more depressed with chlordiazepoxide than with placebo. The findings suggest that there are at least two kinds of anxiety in schizophrenia. A few anxious schizophrenic patients apparently benefit more from a combination of a phenothiazine with chlordiazepoxide than from a phenothiazine alone.", "contents": "Anxiety in schizophrenia. The responses to chlordiazepoxide in an intensive design study. Six anxious schizophrenic patients who were maintained with phenothiazines participated in a double-blind intensive design study of chlordiazepoxide and placebo for 12 weeks or longer. There were substantial differences between patients in their responses to chlordiazepoxide: two patients experienced significant and conspicuous relief of distress and reduction of typical schizophrenic symptoms. In another patient the differences, although statistically significant, were clinically less striking. In the three remaining patients no differences were observed between responses to the two treatments except that one patient was more depressed with chlordiazepoxide than with placebo. The findings suggest that there are at least two kinds of anxiety in schizophrenia. A few anxious schizophrenic patients apparently benefit more from a combination of a phenothiazine with chlordiazepoxide than from a phenothiazine alone."}
{"id": "PMID:241307", "title": "Behavioral Effects of Reducing the Daily Frequency of Phenothiazine Administration.", "content": "After an 11-day base line of behavioral observations, 24 chronic female schizophrenics were assigned to two groups matched for alertness. In the first treatment phase, the administration of phenothiazine medication of one group was switched from a multiple-dose schedule (three to four times per day) to a single daily administration, while the total dosage per day was held constant. The second group continued on a multiple administration schedule for 11 days and then was switched to a single daily dosage. A multivariate analysis of variance showed that there was no overall effect (positive or negative) due to the schedule change; however, preplanned t tests showed transitory decreases in nonfunctional behavior. The results are discussed in terms of implications for the administration of phenothiazines and the experimental analysis of drug effects.", "contents": "Behavioral Effects of Reducing the Daily Frequency of Phenothiazine Administration. After an 11-day base line of behavioral observations, 24 chronic female schizophrenics were assigned to two groups matched for alertness. In the first treatment phase, the administration of phenothiazine medication of one group was switched from a multiple-dose schedule (three to four times per day) to a single daily administration, while the total dosage per day was held constant. The second group continued on a multiple administration schedule for 11 days and then was switched to a single daily dosage. A multivariate analysis of variance showed that there was no overall effect (positive or negative) due to the schedule change; however, preplanned t tests showed transitory decreases in nonfunctional behavior. The results are discussed in terms of implications for the administration of phenothiazines and the experimental analysis of drug effects."}
{"id": "PMID:241308", "title": "The basis for amine hypotheses in affective disorders. A critical evaluation.", "content": "A leading hypothesis concerning a biological basis of the affective disorders is that altered metabolism of brain amines may underlie the cause or pathophysiology of these conditions. Features of affective illnesses supporting biological hypotheses include the somatic symptoms, diurnal rhythm, and apparent \"endogenicity\" of many severe depressions, and evidence of a genetic basis of manic-depressive illness. Development and preclinical study of medical therapies for the disorders substantially supported a relationship between mood-disturbances and neutrotransmitters and stimulated considerable advances in the physiology and pharmacology of central synaptic neurotransmission. Unfortunately, studies of amine metabolism in patients have not provided consistent support for the amine hypotheses. Moreover, these hypotheses have not led to a coherent biological theory of abnormal behavior, to an objective basis for differential diagnosis, or to the rational development of treatments more effective or safer than those known.", "contents": "The basis for amine hypotheses in affective disorders. A critical evaluation. A leading hypothesis concerning a biological basis of the affective disorders is that altered metabolism of brain amines may underlie the cause or pathophysiology of these conditions. Features of affective illnesses supporting biological hypotheses include the somatic symptoms, diurnal rhythm, and apparent \"endogenicity\" of many severe depressions, and evidence of a genetic basis of manic-depressive illness. Development and preclinical study of medical therapies for the disorders substantially supported a relationship between mood-disturbances and neutrotransmitters and stimulated considerable advances in the physiology and pharmacology of central synaptic neurotransmission. Unfortunately, studies of amine metabolism in patients have not provided consistent support for the amine hypotheses. Moreover, these hypotheses have not led to a coherent biological theory of abnormal behavior, to an objective basis for differential diagnosis, or to the rational development of treatments more effective or safer than those known."}
{"id": "PMID:241305", "title": "[Benign neurologic accident following anti-rabies vaccination. Unforeseen clinical and biological aspects].", "content": "A minor and benign encephalitogenic reactions was observed in the days following administration of suckling mouse brain anti-rabies vaccine. The syndrome appeared at the 18th day of the treatment, undertaken according to Gamet and Atanasiu's shortened treatment schedule. Recovery occured without sequellae after 5 days of corticosteroid therapy. Compared to the reports of the literature, the benignity of the central nervous system involvement was unexpected. Three immunological problems are stressed out: the presence of sheep anti-red blood cells antibodies after antirabies vaccines; the presence of antismooth muscle antibodies; a previous BCG vaccination one month before antirabies treatment might play an adjuvant participation.", "contents": "[Benign neurologic accident following anti-rabies vaccination. Unforeseen clinical and biological aspects]. A minor and benign encephalitogenic reactions was observed in the days following administration of suckling mouse brain anti-rabies vaccine. The syndrome appeared at the 18th day of the treatment, undertaken according to Gamet and Atanasiu's shortened treatment schedule. Recovery occured without sequellae after 5 days of corticosteroid therapy. Compared to the reports of the literature, the benignity of the central nervous system involvement was unexpected. Three immunological problems are stressed out: the presence of sheep anti-red blood cells antibodies after antirabies vaccines; the presence of antismooth muscle antibodies; a previous BCG vaccination one month before antirabies treatment might play an adjuvant participation."}
{"id": "PMID:241310", "title": "Antigenic comparison of swine influenza virus isolates.", "content": "Cross hemagglutination inhibition (HI) and neuraminidase inhibition (NI) tests demonstrated strong antigenic relationship between A/Swine/Wisconsin/1/73 (SW/73) and A/Swine/Shope/15/31 (SW/31) influenza viruses. An eigthyone fold purification of virus was achieved by adsorption and elution followed by differential ultracentrifugation and sedimentation through linear sucrose gradient. Radioimmunoassay using purified 125I labeled viral antigens revealed antigenic variation between the two virus isolates. Neuraminidase of both viruses had pH optima between 6.5 and 7.0, and SW/31 enzyme was relatively more heat stable than SW/73.", "contents": "Antigenic comparison of swine influenza virus isolates. Cross hemagglutination inhibition (HI) and neuraminidase inhibition (NI) tests demonstrated strong antigenic relationship between A/Swine/Wisconsin/1/73 (SW/73) and A/Swine/Shope/15/31 (SW/31) influenza viruses. An eigthyone fold purification of virus was achieved by adsorption and elution followed by differential ultracentrifugation and sedimentation through linear sucrose gradient. Radioimmunoassay using purified 125I labeled viral antigens revealed antigenic variation between the two virus isolates. Neuraminidase of both viruses had pH optima between 6.5 and 7.0, and SW/31 enzyme was relatively more heat stable than SW/73."}
{"id": "PMID:241312", "title": "The isolation of aggregates of spectrin from bovine erythrocyte membranes.", "content": "Aggregated states of spectrin from bovine erythrocyte membranes can be detected in sedimentation velocity experiments. These aggregates have been isolated by means of gel filtration on columns of 4% agarose. They appear to be stable over a wide range of pH and ionic strength, although they are dissociated by sodium dodecyl sulphate. Sedimentation equilibrium measurements yielded values of 960 000 and 480 000 for the molecular weights of the major aggregates, corresponding to a tetramer and dimer, respectively. The presence of different aggregated states in spectrin preparations may explain the wide variation in the reported physical properties of spectrin.", "contents": "The isolation of aggregates of spectrin from bovine erythrocyte membranes. Aggregated states of spectrin from bovine erythrocyte membranes can be detected in sedimentation velocity experiments. These aggregates have been isolated by means of gel filtration on columns of 4% agarose. They appear to be stable over a wide range of pH and ionic strength, although they are dissociated by sodium dodecyl sulphate. Sedimentation equilibrium measurements yielded values of 960 000 and 480 000 for the molecular weights of the major aggregates, corresponding to a tetramer and dimer, respectively. The presence of different aggregated states in spectrin preparations may explain the wide variation in the reported physical properties of spectrin."}
{"id": "PMID:241313", "title": "Pyridine nucleosidase in bull semen. II. Biochemical properties.", "content": "It is most likely a single enzyme (NAD+ nucleosidase) present in semen from most bulls which hydrolyses the ribosyl pyridinium bond in both NAD and NADP. This conclusion is based on the following results: (i) each of 12 semen samples containing nucleosidase activity hydrolysed NAD at the same rate as NADP (r = 0.99); (ii) other untreated semen samples from different bulls which did not hydrolyse NAD were also inactive against NADP; (iii) enzyme denaturation produced by preliminary heating of semen filtrates for 15 min at varied temperatures or by heating at 55 degrees C for varied time intervals caused similar reductions in the rates of NAD and NADP hydrolysis; and (iv) nicotinamide inhibited enzyme activity to the same degree using either NAD or NADP as the substrate.", "contents": "Pyridine nucleosidase in bull semen. II. Biochemical properties. It is most likely a single enzyme (NAD+ nucleosidase) present in semen from most bulls which hydrolyses the ribosyl pyridinium bond in both NAD and NADP. This conclusion is based on the following results: (i) each of 12 semen samples containing nucleosidase activity hydrolysed NAD at the same rate as NADP (r = 0.99); (ii) other untreated semen samples from different bulls which did not hydrolyse NAD were also inactive against NADP; (iii) enzyme denaturation produced by preliminary heating of semen filtrates for 15 min at varied temperatures or by heating at 55 degrees C for varied time intervals caused similar reductions in the rates of NAD and NADP hydrolysis; and (iv) nicotinamide inhibited enzyme activity to the same degree using either NAD or NADP as the substrate."}
{"id": "PMID:241314", "title": "Analysis of gases and pH of blood at altitude.", "content": "The accuracy of a system for measuring pH and gas in blood in a changing-altitude environment was studied. No problems were encountered when arterial blood was measured, provided the instrument was properly calibrated. Failure to calibrate to the correct altitude settings caused major variations in measuring oxygen levels in blood. Standard gases used for calibrating were measured at altitude without recalibrating the system; approximately 80% of the oxygen and 90% of the carbon dioxide partial-pressure values were within 3 mm Hg of their expected value. More deviation occurred for Po2 values as the altitude increased. Frequently, the Po2 electrode malfunctioned, particularly above 8000 ft (2438 m). The Corning Blood Gas System, which was used in this study, was capable of making accurate determinations of gas in blood if properly operated and calibrated to specific altitude levels.", "contents": "Analysis of gases and pH of blood at altitude. The accuracy of a system for measuring pH and gas in blood in a changing-altitude environment was studied. No problems were encountered when arterial blood was measured, provided the instrument was properly calibrated. Failure to calibrate to the correct altitude settings caused major variations in measuring oxygen levels in blood. Standard gases used for calibrating were measured at altitude without recalibrating the system; approximately 80% of the oxygen and 90% of the carbon dioxide partial-pressure values were within 3 mm Hg of their expected value. More deviation occurred for Po2 values as the altitude increased. Frequently, the Po2 electrode malfunctioned, particularly above 8000 ft (2438 m). The Corning Blood Gas System, which was used in this study, was capable of making accurate determinations of gas in blood if properly operated and calibrated to specific altitude levels."}
{"id": "PMID:241319", "title": "Comparison of the amino acid sequences of the variable domains of two homogeneous rabbit antibodies to type III pneumococcal polysaccharide.", "content": "The amino acid sequences of the V (variable) regions of the H (heavy) and L (light) chains derived from rabbit antibody K-25, specific for type III pneumococci, were determined; this is the second homogeneous rabbit antibody besides antibody BS-5 whose complete sequence of the V domain has been established (Jaton, 1974d). The V regions of L chains BS-5 and K-25 (both of allotype b4) differ from each other by 19 amino acid residues; 11 of these 19 substitutions are located within the three hypervariable sections of the V region. On the basis of seven amino acid differences within the N-terminal 28 positions, it is suggested that L chain K-25 belongs to a different subgroup of rabbit K chains and L chain BS-5. H chain K-25 (allotype a2) differs from another H chain of the same allotype by one amino acid substitution within the N-terminal 70 positions in addition to interchanges occurring in the first two hypervariable sections. H chain K-25 was compared with H chain BS-5 (allotype a1) and with the known V-region rabbit sequences. Allotype-related differences between a1, a2 and a3 chains appear to occur within the N-terminal 16 positions and possibly in scattered positions throughout the V-region. In the hypervariable positions, variability between the two antibodies is remarkably more pronounced within the third hypervariable section of both H and L chains than within the first two.", "contents": "Comparison of the amino acid sequences of the variable domains of two homogeneous rabbit antibodies to type III pneumococcal polysaccharide. The amino acid sequences of the V (variable) regions of the H (heavy) and L (light) chains derived from rabbit antibody K-25, specific for type III pneumococci, were determined; this is the second homogeneous rabbit antibody besides antibody BS-5 whose complete sequence of the V domain has been established (Jaton, 1974d). The V regions of L chains BS-5 and K-25 (both of allotype b4) differ from each other by 19 amino acid residues; 11 of these 19 substitutions are located within the three hypervariable sections of the V region. On the basis of seven amino acid differences within the N-terminal 28 positions, it is suggested that L chain K-25 belongs to a different subgroup of rabbit K chains and L chain BS-5. H chain K-25 (allotype a2) differs from another H chain of the same allotype by one amino acid substitution within the N-terminal 70 positions in addition to interchanges occurring in the first two hypervariable sections. H chain K-25 was compared with H chain BS-5 (allotype a1) and with the known V-region rabbit sequences. Allotype-related differences between a1, a2 and a3 chains appear to occur within the N-terminal 16 positions and possibly in scattered positions throughout the V-region. In the hypervariable positions, variability between the two antibodies is remarkably more pronounced within the third hypervariable section of both H and L chains than within the first two."}
{"id": "PMID:241320", "title": "The preparation and some properties of mammalian cytochrome c modified with 2-hydroxy-5-nitrobenzyl bromide.", "content": "2-Hydroxy-5-nitrobenzyl bromide reacts with horse heart cytochrome c at acid pH to yield a chemically modified protein. Chromatography of the protein on CM-cellulose allows separation of a single chemically modified species. This species is shown by gel chromatography to be monomeric, and isoelectric focusing shows the pI to be lowered from 10.5 to 9.8 on introduction of the reagent molecule. The changes observed in the u.v. region of the spectrum are consistent with the introduction of a single residue of the reagent, and the normal fluorescence of tryptophan is lost. The chemically modified protein exhibits marked changes in its functional properties as compared with native cytochrome c. Unlike the native monomer, the modified cytochrome c has a pH-dependent spectrum which is typical of a high-spin species in the alpha/beta region at low pH, changing to a low-spin species with an apparent pK of 7.5. The modified protein is autoxidizable and the ferrous form binds CO at neutral pH with an affinity constant of 2.6 X 10(5)M-1. The ferrous form of the modified cytochrome c binds CN- at pH 10.0 with an affinity constant of 3.5 X 10(2)M-1. The modified cytochrome c was incapable of restoring the electron-transfer activity to mitochondria depleted of cytochrome c.", "contents": "The preparation and some properties of mammalian cytochrome c modified with 2-hydroxy-5-nitrobenzyl bromide. 2-Hydroxy-5-nitrobenzyl bromide reacts with horse heart cytochrome c at acid pH to yield a chemically modified protein. Chromatography of the protein on CM-cellulose allows separation of a single chemically modified species. This species is shown by gel chromatography to be monomeric, and isoelectric focusing shows the pI to be lowered from 10.5 to 9.8 on introduction of the reagent molecule. The changes observed in the u.v. region of the spectrum are consistent with the introduction of a single residue of the reagent, and the normal fluorescence of tryptophan is lost. The chemically modified protein exhibits marked changes in its functional properties as compared with native cytochrome c. Unlike the native monomer, the modified cytochrome c has a pH-dependent spectrum which is typical of a high-spin species in the alpha/beta region at low pH, changing to a low-spin species with an apparent pK of 7.5. The modified protein is autoxidizable and the ferrous form binds CO at neutral pH with an affinity constant of 2.6 X 10(5)M-1. The ferrous form of the modified cytochrome c binds CN- at pH 10.0 with an affinity constant of 3.5 X 10(2)M-1. The modified cytochrome c was incapable of restoring the electron-transfer activity to mitochondria depleted of cytochrome c."}
{"id": "PMID:241321", "title": "Ethylenediamine-NN'-tetra-acetate-dependent amino acid-stimulated inactivation of mouse ovarian alkaline phosphatase activity.", "content": "1. Preincubation of partially purified preparations of mouse ovarian alkaline phosphatase in the presence of both EDTA and glycine at alkaline pH resulted in a pronounced inactivation of alkaline phosphatase activity. Inactivation did not occur on preincubation with EDTA or glycine alone. 2. The rate of inactivation was first-order with respect to the concentration of enzyme, and was independent of EDTA concentration above a threshold value. 3. The process was pH-dependent with a pK at 9.85, and inactivation was not dependent on the stereochemistry of the amino acid. A free alpha-amino group and a free carboxyl group at a specific spatial separation were essential for inactivation. 4. Inactivation involved the formation of an enzyme--metal ion--amino acid complex, the amount formed being dependent on both the nature and concentration of the amino acid. This complex then decayed to a derivative that was then acted on by EDTA, yielding an inactive form of the enzyme.", "contents": "Ethylenediamine-NN'-tetra-acetate-dependent amino acid-stimulated inactivation of mouse ovarian alkaline phosphatase activity. 1. Preincubation of partially purified preparations of mouse ovarian alkaline phosphatase in the presence of both EDTA and glycine at alkaline pH resulted in a pronounced inactivation of alkaline phosphatase activity. Inactivation did not occur on preincubation with EDTA or glycine alone. 2. The rate of inactivation was first-order with respect to the concentration of enzyme, and was independent of EDTA concentration above a threshold value. 3. The process was pH-dependent with a pK at 9.85, and inactivation was not dependent on the stereochemistry of the amino acid. A free alpha-amino group and a free carboxyl group at a specific spatial separation were essential for inactivation. 4. Inactivation involved the formation of an enzyme--metal ion--amino acid complex, the amount formed being dependent on both the nature and concentration of the amino acid. This complex then decayed to a derivative that was then acted on by EDTA, yielding an inactive form of the enzyme."}
{"id": "PMID:241322", "title": "Acetylation of S-substituted cysteines by a rat liver and kidney microsomal N-acetyltransferase.", "content": "1. An acetyl-CoA--S-substituted cysteine N-acetyltransferase in rat liver and kidney preparations was investigated, by using an assay involving incubations with S-benzyl-L-cysteine and [l-14C]acetyl-CoA and extraction of the radioactive product with ethyl acetate. 2. The enzyme was associated with the microsomal fraction and could not be solubilized. Metal ions, EDTA and detergents did not significantly affect the enzyme activity. p-Chloromercuribenzoate and N-ethylmaleimide inhibited the enzyme. 3. Other S-substituted cysteines were acetylated at about the same rate as S-benzyl-L-cysteine. Acetylation of cysteine itself and of methionine, ethionine and tryptophan could be detected but was much slower. Acetylation of aspartic acid, glycine, phenylalanine and serine could not be detected. Palmitoyl-CoA was not a substrate. 4. The enzyme is presumably responsible for the acetylation step of mercapturic acid synthesis; a more physiological function is not yet known, except that the enzyme may be involved in acetylation of those amino acids which occur in elevated amounts in some disorders of amino acid metabolism.", "contents": "Acetylation of S-substituted cysteines by a rat liver and kidney microsomal N-acetyltransferase. 1. An acetyl-CoA--S-substituted cysteine N-acetyltransferase in rat liver and kidney preparations was investigated, by using an assay involving incubations with S-benzyl-L-cysteine and [l-14C]acetyl-CoA and extraction of the radioactive product with ethyl acetate. 2. The enzyme was associated with the microsomal fraction and could not be solubilized. Metal ions, EDTA and detergents did not significantly affect the enzyme activity. p-Chloromercuribenzoate and N-ethylmaleimide inhibited the enzyme. 3. Other S-substituted cysteines were acetylated at about the same rate as S-benzyl-L-cysteine. Acetylation of cysteine itself and of methionine, ethionine and tryptophan could be detected but was much slower. Acetylation of aspartic acid, glycine, phenylalanine and serine could not be detected. Palmitoyl-CoA was not a substrate. 4. The enzyme is presumably responsible for the acetylation step of mercapturic acid synthesis; a more physiological function is not yet known, except that the enzyme may be involved in acetylation of those amino acids which occur in elevated amounts in some disorders of amino acid metabolism."}
{"id": "PMID:241323", "title": "A study of the pH- and temperature-dependence of the reactions of yeast alcohol dehydrogenase with ethanol, acetaldehyde and butyraldehyde as substrates.", "content": "The kinetics of ethanol oxidation by NAD+, and acetaldehyde and butyraldehyde reduction by NADH, catalysed by yeast alcohol dehydrogenase, were studied in the pH range 4.9--9.9 at 25 degrees C and in the temperature range 14.8--43.5 degrees C at pH 7.05. The kinetics of reduction of acetaldehyde by [4A-2H]NADH at pH 7.05 and pH 8.9 at 25 degrees C were also studied. The results of the kinetic experiments indicate that the mechanism of catalysis, previously proposed on the basis of studies at pH 7.05 and 25 degrees C (Dickinson & Monger, 1973), applies over the wide range of conditions now tested. Values of some of the initial-rate parameters obtained were used to deduce information about the pH- and temperature-dependence of the specific rates of combination of enzyme and coenzymes and of the dissociation of the enzyme--coenzyme compounds. Primary and secondary plots of initial-rate data are deposited as Supplementary Publication SUP 50043 (20 pages) with the British Library (Lending Division), Boston Spa, Wetherby, Yorks. LS23 7BQ, U.K., from whom copies may be obtained under the terms indicated in Biochem. J. (1975) 145, 5.", "contents": "A study of the pH- and temperature-dependence of the reactions of yeast alcohol dehydrogenase with ethanol, acetaldehyde and butyraldehyde as substrates. The kinetics of ethanol oxidation by NAD+, and acetaldehyde and butyraldehyde reduction by NADH, catalysed by yeast alcohol dehydrogenase, were studied in the pH range 4.9--9.9 at 25 degrees C and in the temperature range 14.8--43.5 degrees C at pH 7.05. The kinetics of reduction of acetaldehyde by [4A-2H]NADH at pH 7.05 and pH 8.9 at 25 degrees C were also studied. The results of the kinetic experiments indicate that the mechanism of catalysis, previously proposed on the basis of studies at pH 7.05 and 25 degrees C (Dickinson & Monger, 1973), applies over the wide range of conditions now tested. Values of some of the initial-rate parameters obtained were used to deduce information about the pH- and temperature-dependence of the specific rates of combination of enzyme and coenzymes and of the dissociation of the enzyme--coenzyme compounds. Primary and secondary plots of initial-rate data are deposited as Supplementary Publication SUP 50043 (20 pages) with the British Library (Lending Division), Boston Spa, Wetherby, Yorks. LS23 7BQ, U.K., from whom copies may be obtained under the terms indicated in Biochem. J. (1975) 145, 5."}
{"id": "PMID:241324", "title": "The purification and properties of L-histidine--2-oxoglutarate aminotransferase from Pseudomonas testosteroni.", "content": "1. Inducible L-histidine--2-oxoglutarate aminotransferase was purified some 170-fold from extracts of Pseudomonas testosteroni. 2. The preparation showed only one major component after electrophoresis on polyacrylamide gels, though additional minor bands were observed when samples concentrated on a DEAE-cellulose column were used. 3. The molecular weight of the enzyme was found to be approx. 70000 by chromatography on Sephadex G-200. 4. The purification scheme produced enzyme that was inactive in the absence of pyridoxal 5'-phosphate. 5. The equilibrium constant for the reaction L-histidine+2-oxoglutarate equilibrium  imidazolylpyruvate+L-glutamate was 0.49. 6. The reaction mechanism was Ping Pong. 7. The enzyme was shown to have only low activity towards aromatic amino acids and was highly specific for 2-oxoglutarate.", "contents": "The purification and properties of L-histidine--2-oxoglutarate aminotransferase from Pseudomonas testosteroni. 1. Inducible L-histidine--2-oxoglutarate aminotransferase was purified some 170-fold from extracts of Pseudomonas testosteroni. 2. The preparation showed only one major component after electrophoresis on polyacrylamide gels, though additional minor bands were observed when samples concentrated on a DEAE-cellulose column were used. 3. The molecular weight of the enzyme was found to be approx. 70000 by chromatography on Sephadex G-200. 4. The purification scheme produced enzyme that was inactive in the absence of pyridoxal 5'-phosphate. 5. The equilibrium constant for the reaction L-histidine+2-oxoglutarate equilibrium  imidazolylpyruvate+L-glutamate was 0.49. 6. The reaction mechanism was Ping Pong. 7. The enzyme was shown to have only low activity towards aromatic amino acids and was highly specific for 2-oxoglutarate."}
{"id": "PMID:241325", "title": "Ligand binding to ferrocytochrome c at high pH.", "content": "Ferrocytochrome c has been shown to bind two molecules of CO at pH 14. The second CO is thought to be bound only when the cytochrome c molecule is denatured, and once bound appears to be spectrally silent. Insolubilization of native cytochrome c prevents the binding of the second CO molecule. A scheme is proposed to explain these observations based on evidence from static titrations and flash-photolysis experiments, use of carboxymethyl cytochrome c and insoluble cytochrome c, and use of cyanide instead of CO as a ligand.", "contents": "Ligand binding to ferrocytochrome c at high pH. Ferrocytochrome c has been shown to bind two molecules of CO at pH 14. The second CO is thought to be bound only when the cytochrome c molecule is denatured, and once bound appears to be spectrally silent. Insolubilization of native cytochrome c prevents the binding of the second CO molecule. A scheme is proposed to explain these observations based on evidence from static titrations and flash-photolysis experiments, use of carboxymethyl cytochrome c and insoluble cytochrome c, and use of cyanide instead of CO as a ligand."}
{"id": "PMID:241326", "title": "A study of the kinetics of iron and copper binding to hen ovotransferrin.", "content": "The kinetics of iron and copper binding to hen's-egg apo-ovotransferrin were studied by using citrate chelates of these metals at pH9.3 in borate buffer in the presence of bicarbonate. The kinetics of the absorbance change associated with the formation of the final product show a fast process, which is pseudo-first-order, where the reagents are in excess with respect to the protein, and the citrate concentration is higher than 25mM. At lower citrate concentration, the progress curves are clearly biphasic. There is marked dependence of the rate of the reaction on bicarbonate concentration, which may be interpreted as a displacement reaction of the ligand-metal-protein ternary complex. The kinetics have been interpreted in the framework of a reaction scheme which involves bimolecular reaction of a metal chelate to the protein and subsequent colour development by displacement of the chelator by bicarbonate. The pH-dependence of this reaction supports the belief that tyrosine residues are involved in the process of iron-binding. The overall similarity of kinetics for iron and copper binding, notwithstanding their different co-ordination preferences, suggests that the process of metal-binding or chromophore development for the two metal complexes must be similar.", "contents": "A study of the kinetics of iron and copper binding to hen ovotransferrin. The kinetics of iron and copper binding to hen's-egg apo-ovotransferrin were studied by using citrate chelates of these metals at pH9.3 in borate buffer in the presence of bicarbonate. The kinetics of the absorbance change associated with the formation of the final product show a fast process, which is pseudo-first-order, where the reagents are in excess with respect to the protein, and the citrate concentration is higher than 25mM. At lower citrate concentration, the progress curves are clearly biphasic. There is marked dependence of the rate of the reaction on bicarbonate concentration, which may be interpreted as a displacement reaction of the ligand-metal-protein ternary complex. The kinetics have been interpreted in the framework of a reaction scheme which involves bimolecular reaction of a metal chelate to the protein and subsequent colour development by displacement of the chelator by bicarbonate. The pH-dependence of this reaction supports the belief that tyrosine residues are involved in the process of iron-binding. The overall similarity of kinetics for iron and copper binding, notwithstanding their different co-ordination preferences, suggests that the process of metal-binding or chromophore development for the two metal complexes must be similar."}
{"id": "PMID:241327", "title": "Properties of the histidine residues of indole-chymotrypsin. Implications for the activation process and catalytic mechanism.", "content": "The use of a linear free-energy relationship shows that both histidine residues of alpha-chymotrypsin and chymotrypsinogen are super-reactive toward 1-fluoro-2,4-dinitrobenzene. The binding of indole to the specificity site of alpha-chymotrypsin causes both histidine residues to become less reactive. On the basis of these results and those from X-ray-crystallographic studies, the following conclusions are made. (1) The super-reactivity of the catalytic-site histidine-57 is due to charge transfer from aspartic acid-102 by means of hydrogen bonding. (2) The aspartic acid-102-histidine-57-serine-195 'charge-relay' system is not complete in the zymogen or native enzyme and only on binding of a suitable substrate or ligand to the specificity site of the enzyme is the charge transfer to serine-195 completed. (3) The lack of substantial enzymic activity in the zymogen is due to the absence of a completed specificity site, and therefore it cannot bind suitable substrates or ligands to induce completion of the charge-relay system.", "contents": "Properties of the histidine residues of indole-chymotrypsin. Implications for the activation process and catalytic mechanism. The use of a linear free-energy relationship shows that both histidine residues of alpha-chymotrypsin and chymotrypsinogen are super-reactive toward 1-fluoro-2,4-dinitrobenzene. The binding of indole to the specificity site of alpha-chymotrypsin causes both histidine residues to become less reactive. On the basis of these results and those from X-ray-crystallographic studies, the following conclusions are made. (1) The super-reactivity of the catalytic-site histidine-57 is due to charge transfer from aspartic acid-102 by means of hydrogen bonding. (2) The aspartic acid-102-histidine-57-serine-195 'charge-relay' system is not complete in the zymogen or native enzyme and only on binding of a suitable substrate or ligand to the specificity site of the enzyme is the charge transfer to serine-195 completed. (3) The lack of substantial enzymic activity in the zymogen is due to the absence of a completed specificity site, and therefore it cannot bind suitable substrates or ligands to induce completion of the charge-relay system."}
{"id": "PMID:241328", "title": "Preparation of polyribosome aminoacyl-transfer ribonucleic acid from the muscle of chick embryos.", "content": "A procedure for preparing polyribosome aminoacyl-tRNA free from contamination by supernatant aminoacyl-tRNA and free amino acids is described. Important features of the procedure are the use of acidic buffers to help protect the amino acid-tRNA linkage and the inclusion of sodium dodecyl sulphate, to inhibit ribonuclease activity. The specific radioactivity of polyribosome aminoacyl-tRNA is high within 30s and reaches a maximum in 2 1/2 min, well ahead of polyribosome peptides which, as described by Herrmann et al. (1971), attain maximum specific radioactivity in about 10 min.", "contents": "Preparation of polyribosome aminoacyl-transfer ribonucleic acid from the muscle of chick embryos. A procedure for preparing polyribosome aminoacyl-tRNA free from contamination by supernatant aminoacyl-tRNA and free amino acids is described. Important features of the procedure are the use of acidic buffers to help protect the amino acid-tRNA linkage and the inclusion of sodium dodecyl sulphate, to inhibit ribonuclease activity. The specific radioactivity of polyribosome aminoacyl-tRNA is high within 30s and reaches a maximum in 2 1/2 min, well ahead of polyribosome peptides which, as described by Herrmann et al. (1971), attain maximum specific radioactivity in about 10 min."}
{"id": "PMID:241329", "title": "Purification and properties of S-alkyl-L-cysteine lyase from seedlings of Acacia farnesiana Willd.", "content": "1. An S-alkyl-L-cysteine lyase (EC 4.4.1.6) was purified to apparent homogeneity from extracts of acetone-dried powders of the hypocotyls of etiolated 5-day-old seedlings of Acacia farnesiana Willd. 2. The enzyme catalyses a beta-elimination reaction and will utilize both the thioether and sulphoxide form of the substrate. 3. There is a braod specificity with regard to the alkyl substituent, but cystathionine is utilized very poorly. 4. The pH optimum is 7.8 and the Km value for the probable natural substrate L-djenkolate is 0.3 mM. 5. Both sodium dodecyl sulphate-polyacrylamide-gel electrophoresis and ultracentirfugal analysis give a molecular weight of about 144000. 6. One mol of pyridoxal phosphate is bound/mol of enzyme. 7. The energy of activation with L-djenkolate as the substrate is 53.1 kJ/mol. 8. The enzyme has a partial specific volume of 0.56 and S20,w 7.26S.", "contents": "Purification and properties of S-alkyl-L-cysteine lyase from seedlings of Acacia farnesiana Willd. 1. An S-alkyl-L-cysteine lyase (EC 4.4.1.6) was purified to apparent homogeneity from extracts of acetone-dried powders of the hypocotyls of etiolated 5-day-old seedlings of Acacia farnesiana Willd. 2. The enzyme catalyses a beta-elimination reaction and will utilize both the thioether and sulphoxide form of the substrate. 3. There is a braod specificity with regard to the alkyl substituent, but cystathionine is utilized very poorly. 4. The pH optimum is 7.8 and the Km value for the probable natural substrate L-djenkolate is 0.3 mM. 5. Both sodium dodecyl sulphate-polyacrylamide-gel electrophoresis and ultracentirfugal analysis give a molecular weight of about 144000. 6. One mol of pyridoxal phosphate is bound/mol of enzyme. 7. The energy of activation with L-djenkolate as the substrate is 53.1 kJ/mol. 8. The enzyme has a partial specific volume of 0.56 and S20,w 7.26S."}
{"id": "PMID:241330", "title": "Selective inhibition of cholesterol synthesis by cell-free preparations of rat liver by using inhibitors of cytoplasmic acetoacetyl-coenzyme A thiolase.", "content": "Cytoplasmic acetoacetyl-CoA thiolase (acetyl-CoA C-acetyltransferase, EC 2.3.1.9) was partially purified from rat liver. The enzyme was irreversibly inactivated by 4-bromocrotonyl-CoA, but-3-ynoyl-CoA, pent-3-ynoyl-CoA and dec-3-ynoyl-CoA. In the case of the alk-3-ynoyl-CoA esters the potency as alkylating agents of acetoacetyl-CoA thiolase decreased with increased chain length of the alk-3-ynoyl moiety. Advantage was taken of the specific action of alk-3-ynoyl-CoA esters on acetoacetyl-CoA thiolase to show that in a postmitochondrial fraction from rat liver they are effective inhibitors of cholesterol synthesis from sodium [2-14C]acetate under conditions when mevalonate conversion into cholesterol and fatty acid synthesis are unafffected. Short-chain alk-3-ynoic acids have little effect on sterol synthesis, although dec-3-ynoic acid is an effective inhibitor owing to its conversion into the CoA ester by the microsomal fatty acyl-CoA synthetase.", "contents": "Selective inhibition of cholesterol synthesis by cell-free preparations of rat liver by using inhibitors of cytoplasmic acetoacetyl-coenzyme A thiolase. Cytoplasmic acetoacetyl-CoA thiolase (acetyl-CoA C-acetyltransferase, EC 2.3.1.9) was partially purified from rat liver. The enzyme was irreversibly inactivated by 4-bromocrotonyl-CoA, but-3-ynoyl-CoA, pent-3-ynoyl-CoA and dec-3-ynoyl-CoA. In the case of the alk-3-ynoyl-CoA esters the potency as alkylating agents of acetoacetyl-CoA thiolase decreased with increased chain length of the alk-3-ynoyl moiety. Advantage was taken of the specific action of alk-3-ynoyl-CoA esters on acetoacetyl-CoA thiolase to show that in a postmitochondrial fraction from rat liver they are effective inhibitors of cholesterol synthesis from sodium [2-14C]acetate under conditions when mevalonate conversion into cholesterol and fatty acid synthesis are unafffected. Short-chain alk-3-ynoic acids have little effect on sterol synthesis, although dec-3-ynoic acid is an effective inhibitor owing to its conversion into the CoA ester by the microsomal fatty acyl-CoA synthetase."}
{"id": "PMID:241331", "title": "pH-dependence of 13C chemical shifts and 13C,H coupling constants in imidazole and L-histidine.", "content": "The pH-dependence of selected 13C chemical shifts reflects the state of ionization of the imidazole ring in both imidazole and L-histidine. Titration of the amino and carboxyl groups of histidine also perturbs the shifts. The coupling constants 1J (13C(2),H) and 1J (13C(5),H) for both compounds also vary with pH, but in L-histidine these constants are relatively insensitive to the titration of groups outside the imidazole ring.", "contents": "pH-dependence of 13C chemical shifts and 13C,H coupling constants in imidazole and L-histidine. The pH-dependence of selected 13C chemical shifts reflects the state of ionization of the imidazole ring in both imidazole and L-histidine. Titration of the amino and carboxyl groups of histidine also perturbs the shifts. The coupling constants 1J (13C(2),H) and 1J (13C(5),H) for both compounds also vary with pH, but in L-histidine these constants are relatively insensitive to the titration of groups outside the imidazole ring."}
{"id": "PMID:241332", "title": "Hydrodynamic changes accompanying the loss of metal ions from concanavalin A.", "content": "The hydrodynamic changes which accompany the dissociation of metal ions, from concanavalin A at acid pH are a result of charge effects rather than of dissociation of metal ions as such. Measurements of the rotational relaxation time are discussed in terms of the hydration of the protein and its polymeric heterogeneity.", "contents": "Hydrodynamic changes accompanying the loss of metal ions from concanavalin A. The hydrodynamic changes which accompany the dissociation of metal ions, from concanavalin A at acid pH are a result of charge effects rather than of dissociation of metal ions as such. Measurements of the rotational relaxation time are discussed in terms of the hydration of the protein and its polymeric heterogeneity."}
{"id": "PMID:241333", "title": "Higher-plant cyclic nucleotide phosphodiesterases. Resolution, partial purification and properties of three phosphodiesterases from potato tuber.", "content": "1. Three phosphodiesterases that are capable of hydrolysing 3':5'-cyclic nucleotides were purified from potato tubers. 2. The phosphodiesterases were fractionated by (NH4)2SO4 precipitation and CM-cellulose chromatography. The phosphodiesterases were resolved from each other and further purified by gel filtration in high- and low-ionic-strength conditions. 3. All three enzymes lacked significant nucleotidase activity. 4. Enzymes I and II had mol. wts. 240,000 and 80,000 respectively, determined by gel filtration, whereas enzyme III showed anomalous behaviour on gel filtration, behaving as a high- or low-molecular-weight protein in high- or low-ionic-strength buffers respectively. 5. All enzymes hydrolysed 2':3'-cyclic nucleotides as well as 3':5'-cyclic nucleotides. The enzymes also had nucleotide pyrophosphatase activity, hydrolysing NAD+ and UDP-glucose to various extents. Enzymes I and II hydrolyse cyclic nucleotides at a greater rate than NAD+, whereas enzyme III hydrolyses NAD+ at a much greater rate than cyclic nucleotides. All three enzymes hydrolysed the artificial substrate bis-(p-nitro-phenyl) phosphate. 6. The enzymes do not require the addition of bivalent cations for activity. 7. Both enzymes I and II have optimum activity at pH6 with 3':5'-cyclic AMP and bis-(p-nitrophenyl) phosphate as substrates. The products of 3':5'-cyclic AMP hydrolysis were 3'-AMP and 5'-AMP, the ratio of the two products being different for each enzyme and varying with pH. 8. Theophylline inhibits enzymes I and II slightly, but other methyl xanthines have little effect. Enzymes I and II were competitively inhibited by many nucleotides containing phosphomonoester and phosphodiester bonds, as well as by Pi. 9. The possible significance of these phosphodiesterases in cyclic nucleotide metabolism in higher plants is discussed.", "contents": "Higher-plant cyclic nucleotide phosphodiesterases. Resolution, partial purification and properties of three phosphodiesterases from potato tuber. 1. Three phosphodiesterases that are capable of hydrolysing 3':5'-cyclic nucleotides were purified from potato tubers. 2. The phosphodiesterases were fractionated by (NH4)2SO4 precipitation and CM-cellulose chromatography. The phosphodiesterases were resolved from each other and further purified by gel filtration in high- and low-ionic-strength conditions. 3. All three enzymes lacked significant nucleotidase activity. 4. Enzymes I and II had mol. wts. 240,000 and 80,000 respectively, determined by gel filtration, whereas enzyme III showed anomalous behaviour on gel filtration, behaving as a high- or low-molecular-weight protein in high- or low-ionic-strength buffers respectively. 5. All enzymes hydrolysed 2':3'-cyclic nucleotides as well as 3':5'-cyclic nucleotides. The enzymes also had nucleotide pyrophosphatase activity, hydrolysing NAD+ and UDP-glucose to various extents. Enzymes I and II hydrolyse cyclic nucleotides at a greater rate than NAD+, whereas enzyme III hydrolyses NAD+ at a much greater rate than cyclic nucleotides. All three enzymes hydrolysed the artificial substrate bis-(p-nitro-phenyl) phosphate. 6. The enzymes do not require the addition of bivalent cations for activity. 7. Both enzymes I and II have optimum activity at pH6 with 3':5'-cyclic AMP and bis-(p-nitrophenyl) phosphate as substrates. The products of 3':5'-cyclic AMP hydrolysis were 3'-AMP and 5'-AMP, the ratio of the two products being different for each enzyme and varying with pH. 8. Theophylline inhibits enzymes I and II slightly, but other methyl xanthines have little effect. Enzymes I and II were competitively inhibited by many nucleotides containing phosphomonoester and phosphodiester bonds, as well as by Pi. 9. The possible significance of these phosphodiesterases in cyclic nucleotide metabolism in higher plants is discussed."}
{"id": "PMID:241334", "title": "Unidirectional inhibition and activation of \"malic' enzyme of Solanum tuberosum by meso-tartrate.", "content": "A kinetic study of \"malic' enzyme (EC 1.1.1.40) from potato suggests that the mechanism is Ordered Bi Ter with NADP+ binding before malate, and NADPH binding before pyruvate and HCO3-. The analysis is complicated by the non-linearity that occurs in some of the plots. meso-Tartrate is shown to inhibit the oxidative decarboxylation of malate but to activate the reductive carboxylation of pyruvate. To explain these unidirectional effects it is suggested that the control site of \"malic' enzyme binds organic acids (including meso-tartrate) which activate the enzyme. meso-Tartrate, however, competes with malate for the active site and thus inhibits the oxidative decarboxylation of malate. Because meso-tartrate does not compete effectively with pyruvate for enzyme-NADPH, its binding at the control site leads to a stimulation of the carboxylation of pyruvate. A similar explanation is advanced for the observation that malic acid stimulates its own synthesis.", "contents": "Unidirectional inhibition and activation of \"malic' enzyme of Solanum tuberosum by meso-tartrate. A kinetic study of \"malic' enzyme (EC 1.1.1.40) from potato suggests that the mechanism is Ordered Bi Ter with NADP+ binding before malate, and NADPH binding before pyruvate and HCO3-. The analysis is complicated by the non-linearity that occurs in some of the plots. meso-Tartrate is shown to inhibit the oxidative decarboxylation of malate but to activate the reductive carboxylation of pyruvate. To explain these unidirectional effects it is suggested that the control site of \"malic' enzyme binds organic acids (including meso-tartrate) which activate the enzyme. meso-Tartrate, however, competes with malate for the active site and thus inhibits the oxidative decarboxylation of malate. Because meso-tartrate does not compete effectively with pyruvate for enzyme-NADPH, its binding at the control site leads to a stimulation of the carboxylation of pyruvate. A similar explanation is advanced for the observation that malic acid stimulates its own synthesis."}
{"id": "PMID:241335", "title": "Affinity chromatography of immobilized actin and myosin.", "content": "Actin and myosin were immobilized by coupling them to agarose matrices. Both immobilized G-actin and immobilized myosin retain most of the properties of the proteins in free solution and are reliable over long periods of time. Sepharose-F-actin, under the conditions used in this study, has proved unstable and variable in its properties. Sepharose-G-actin columns were used to bind heavy meromyosin and myosin subfragment 1 specifically and reversibly. The interaction involved is sensitive to variation in ionic strength, such that myosin itself is not retained by the columns at the high salt concentration required for its complete solubilization. Myosin, rendered soluble at low ionic strength by polyalanylation, will interact successfully with the immobilized actin. The latter can distinguish between active and inactive fractions of the proteolytic and polyalanyl myosin derivatives, and was used in the preparation of these molecules. The complexes formed between the myosin derivatives and Sepharose-G-actin can be dissociated by low concentrations of ATP, ADP and pyrophosphate in both the presence and the absence of Mg2+. The G-actin columns were used to evaluate the results of chemical modifications of myosin subfragments on their interactions with actin. F-Actin in free solution is bound specifically and reversibly to columns of insolubilized myosin. Thus, with elution by either ATP or pyrophosphate, actin has been purified in one step from extracts of acetone-dried muscle powder.", "contents": "Affinity chromatography of immobilized actin and myosin. Actin and myosin were immobilized by coupling them to agarose matrices. Both immobilized G-actin and immobilized myosin retain most of the properties of the proteins in free solution and are reliable over long periods of time. Sepharose-F-actin, under the conditions used in this study, has proved unstable and variable in its properties. Sepharose-G-actin columns were used to bind heavy meromyosin and myosin subfragment 1 specifically and reversibly. The interaction involved is sensitive to variation in ionic strength, such that myosin itself is not retained by the columns at the high salt concentration required for its complete solubilization. Myosin, rendered soluble at low ionic strength by polyalanylation, will interact successfully with the immobilized actin. The latter can distinguish between active and inactive fractions of the proteolytic and polyalanyl myosin derivatives, and was used in the preparation of these molecules. The complexes formed between the myosin derivatives and Sepharose-G-actin can be dissociated by low concentrations of ATP, ADP and pyrophosphate in both the presence and the absence of Mg2+. The G-actin columns were used to evaluate the results of chemical modifications of myosin subfragments on their interactions with actin. F-Actin in free solution is bound specifically and reversibly to columns of insolubilized myosin. Thus, with elution by either ATP or pyrophosphate, actin has been purified in one step from extracts of acetone-dried muscle powder."}
{"id": "PMID:241336", "title": "Effect of environmental stress of low pressure on tyrosine aminotransferase and phenylalanine 4-hydroxylase activities in the rat.", "content": "1. Tyrosine aminotransferase activity in the liver increased about fourfold after 9h, on exposure of rats to stress of low pressure. 2. The phenylalanine hydroxylase activity increased about 60% on exposure for 24h or more. 3. An environmental pressure decrease of about 0.033 MN/m2 is needed to increase the activity of tyrosine aminotransferase. 4. Adrenalectomy completely abolished the increase in activity of tyrosine aminotransferase obtained on exposure to low pressure. 5. Treatment with cycloheximide or actinomycin D prevented the increase in activity of tyrosine aminotransferase. 6. Treatment with cycloheximide at the early part of exposure to stress prevented the increase in activity of phenylalanine hydroxylase obtained after 24h.", "contents": "Effect of environmental stress of low pressure on tyrosine aminotransferase and phenylalanine 4-hydroxylase activities in the rat. 1. Tyrosine aminotransferase activity in the liver increased about fourfold after 9h, on exposure of rats to stress of low pressure. 2. The phenylalanine hydroxylase activity increased about 60% on exposure for 24h or more. 3. An environmental pressure decrease of about 0.033 MN/m2 is needed to increase the activity of tyrosine aminotransferase. 4. Adrenalectomy completely abolished the increase in activity of tyrosine aminotransferase obtained on exposure to low pressure. 5. Treatment with cycloheximide or actinomycin D prevented the increase in activity of tyrosine aminotransferase. 6. Treatment with cycloheximide at the early part of exposure to stress prevented the increase in activity of phenylalanine hydroxylase obtained after 24h."}
{"id": "PMID:241352", "title": "A study of the effects of propranolol and/or K 1366 on the distribution of Rb86 clearance in the canine heart under selective coronary hypotension.", "content": "Effects of beta-blockers o-[2-hydroxy-3-(tert.-butylamino)-propoxy]-benzonitrile (K\u00f6 136 1366) and propranolol, on regional Rb86 clearance in the dog myocardium under selective coronary hypotension were investigated. Selective coronary hypotension of the left circumflex artery below 50 mmHg significantly decreased the Rb86 clearance and its I/O ratio of the involved myocardium. K\u00f6 1366 and propranolol had a general trend to decrease the regional Rb86 clearance in the non-ischaemic region and to increase it in the ischaemic region when compared with that of the control group. Therefore, the gradient of regional Rb86 clearance between the non-ischaemic and ischaemic region may decrease. However, these changes were not statistically significant. Although both K\u00f6 1366 and propranolol groups demonstrated similar haemodynamic changes, a reduction in heart rate was larger with propranolol infusion than with K\u00f6 1366. On the contrary, a decreasing rate in systemic arterial blood pressure was marked with K\u00f6 1366. Epicardial ECG ST elevation was reduced after propranolol infusion, not after saline or KO 1366 infusion.", "contents": "A study of the effects of propranolol and/or K 1366 on the distribution of Rb86 clearance in the canine heart under selective coronary hypotension. Effects of beta-blockers o-[2-hydroxy-3-(tert.-butylamino)-propoxy]-benzonitrile (K\u00f6 136 1366) and propranolol, on regional Rb86 clearance in the dog myocardium under selective coronary hypotension were investigated. Selective coronary hypotension of the left circumflex artery below 50 mmHg significantly decreased the Rb86 clearance and its I/O ratio of the involved myocardium. K\u00f6 1366 and propranolol had a general trend to decrease the regional Rb86 clearance in the non-ischaemic region and to increase it in the ischaemic region when compared with that of the control group. Therefore, the gradient of regional Rb86 clearance between the non-ischaemic and ischaemic region may decrease. However, these changes were not statistically significant. Although both K\u00f6 1366 and propranolol groups demonstrated similar haemodynamic changes, a reduction in heart rate was larger with propranolol infusion than with K\u00f6 1366. On the contrary, a decreasing rate in systemic arterial blood pressure was marked with K\u00f6 1366. Epicardial ECG ST elevation was reduced after propranolol infusion, not after saline or KO 1366 infusion."}
{"id": "PMID:241353", "title": "[Studies on the binding of some parasympatholytics to bovine serum albumin/measurement of relaxation times (author's transl)].", "content": "The interactions of the parasympatholytic drugs adiphenin, adiphenin H and propantheline and the structurally related compounds diphenhydramine, D-propoxyphene and methadone with bovine serum albumin (BSA) are studied by means of 1H-NMR-spectroscopy. The relaxation rates of essential protons or proton groups of the bound ligands are obtained by a plot of the observed relaxation rates, which are determined from the alterations of the line widths in the presence of BSA, versus the biopolymer concentration. From the stabilization factors R thus obtained it can be concluded that there exist defined but relatively weak associations between these drugs and BSA; both the hydrophobic aryl moieties and the ionized amino groups are involved in these interactions.", "contents": "[Studies on the binding of some parasympatholytics to bovine serum albumin/measurement of relaxation times (author's transl)]. The interactions of the parasympatholytic drugs adiphenin, adiphenin H and propantheline and the structurally related compounds diphenhydramine, D-propoxyphene and methadone with bovine serum albumin (BSA) are studied by means of 1H-NMR-spectroscopy. The relaxation rates of essential protons or proton groups of the bound ligands are obtained by a plot of the observed relaxation rates, which are determined from the alterations of the line widths in the presence of BSA, versus the biopolymer concentration. From the stabilization factors R thus obtained it can be concluded that there exist defined but relatively weak associations between these drugs and BSA; both the hydrophobic aryl moieties and the ionized amino groups are involved in these interactions."}
{"id": "PMID:241354", "title": "Determination of bromazepam in plasma with an internal standard by gas-liquid chromatography.", "content": "A gaschromatographic assay method is described for the determination of Ro 5-3350 (bromazepam) using Ro 5-4547 (methylbromazepam) as internal standard. After alkaline ether extraction the bromazepam and methylbromazepam obtained from sulfuric acid reextraction are hydrolyzed to ABBP and to MABBP, respectively. After neutralization, the bromo-pyridine-benzophenones are extracted with ether and dissolved in hexane after evaporation of the ether. Under the described gaschromatographic conditions it was found that MABBP and ABBP have retention times of 10.5 and 12.5 min, respectively. The limit of sensitivity is situated at 5 ng/ml of plasma. The specificity is satisfactory since the metabolite which might have interfered (hydroxy-3-bromazepam) appears only at very low concentrations in the blood. The linearity of the calibration curve was confirmed for plasma concentrations up to 100 ng/ml.", "contents": "Determination of bromazepam in plasma with an internal standard by gas-liquid chromatography. A gaschromatographic assay method is described for the determination of Ro 5-3350 (bromazepam) using Ro 5-4547 (methylbromazepam) as internal standard. After alkaline ether extraction the bromazepam and methylbromazepam obtained from sulfuric acid reextraction are hydrolyzed to ABBP and to MABBP, respectively. After neutralization, the bromo-pyridine-benzophenones are extracted with ether and dissolved in hexane after evaporation of the ether. Under the described gaschromatographic conditions it was found that MABBP and ABBP have retention times of 10.5 and 12.5 min, respectively. The limit of sensitivity is situated at 5 ng/ml of plasma. The specificity is satisfactory since the metabolite which might have interfered (hydroxy-3-bromazepam) appears only at very low concentrations in the blood. The linearity of the calibration curve was confirmed for plasma concentrations up to 100 ng/ml."}
{"id": "PMID:241355", "title": "Interaction of homopyrimidazole derivatives with biopolymers. I. Binding of MZ 144, a new potent analgesic to human serum albumin.", "content": "The binding of 1,6-dimethyl-3-carbethoxy-4-oxo-6,7,8,9-tetrahydro-homopyrimidazolium-methyl-sulfate (MZ 144, Probon) to human serum albumin (HSA) has been studied in vitro. The measurements have been performed mostly by means of the classical equilibrium dialysis method. Initially several controls were run to estimate the binding of drug to Visking membrane, time required for equilibrium and to check the stability of the drug at different pH. In addition binding was studied spectrophotometrically, essentially following the method of Klotz. Treatment of binding data was based on the equation developed by Scatchard. The data obtained do not fit the single-site binding equation but could be resolved by a computer program into two sets of binding sites. At pH 7,35,4 degrees C and using a 1% HSA solution values found for binding parameters were: N1 = 0.4359, k1 = 4077 M(-1), N2 = 1.17, k2 = 424 M(-1). Protein binding is considered to have a strong effect on drug distribution only if the affinity constant for the drug, k, has a value greater than 1 times 10(4). The HSA-MZ 144 interaction is temperature dependent and pH dependent.  The percentage bound as a function of total drug concentration was calculated at pH 4.96, 7.35 and 8.5; a considerable increase was observed at pH 8.5.", "contents": "Interaction of homopyrimidazole derivatives with biopolymers. I. Binding of MZ 144, a new potent analgesic to human serum albumin. The binding of 1,6-dimethyl-3-carbethoxy-4-oxo-6,7,8,9-tetrahydro-homopyrimidazolium-methyl-sulfate (MZ 144, Probon) to human serum albumin (HSA) has been studied in vitro. The measurements have been performed mostly by means of the classical equilibrium dialysis method. Initially several controls were run to estimate the binding of drug to Visking membrane, time required for equilibrium and to check the stability of the drug at different pH. In addition binding was studied spectrophotometrically, essentially following the method of Klotz. Treatment of binding data was based on the equation developed by Scatchard. The data obtained do not fit the single-site binding equation but could be resolved by a computer program into two sets of binding sites. At pH 7,35,4 degrees C and using a 1% HSA solution values found for binding parameters were: N1 = 0.4359, k1 = 4077 M(-1), N2 = 1.17, k2 = 424 M(-1). Protein binding is considered to have a strong effect on drug distribution only if the affinity constant for the drug, k, has a value greater than 1 times 10(4). The HSA-MZ 144 interaction is temperature dependent and pH dependent.  The percentage bound as a function of total drug concentration was calculated at pH 4.96, 7.35 and 8.5; a considerable increase was observed at pH 8.5."}
{"id": "PMID:241356", "title": "Pharmacological studies of 1-(o-chlorophenyl)-2-tert.-butylaminoethanol (C-78), a new bonchodilator.", "content": "The bronchodilating effects and other related pharmacological properties of 1-(o-chlorophenyl)-2-tert.-butylaminoethanol-hydrochloride (C-78) were studied in comparison with those of isoproterenol, salbutamol and clorprenaline. C-78 was found to produce a bronchodilating effect 2--10 times stronger and considerably weaker than clorprenaline and isoproterenol, respectively. However, the bronchodilating effect of C-78 was sustained more than 10 times as long as those of isoproterenol and sulbutamol and, especially on oral administration, it was much more potent. The bronchodilating effect of C-78 seems to be due to excitation of the adrenergic beta-receptor, and was antagonized by propranolol. The positive chronotropic and inotropic effects of C-78 on an isolated atrial preparation were less than 1/1000 as potent as those of isoproterenol. C-78 also decreased the tone of smooth muscle, such as the uterus, but its affinity for the bronchial muscle is much higher than for the uterus. C-78 showed strong anti-anaphylactic action and strongly promoted the tracheal ciliary movement. Anitussive effect was also demonstrated, though this was inferior to that of codeine, however, there was no influence on bronchosecretion.", "contents": "Pharmacological studies of 1-(o-chlorophenyl)-2-tert.-butylaminoethanol (C-78), a new bonchodilator. The bronchodilating effects and other related pharmacological properties of 1-(o-chlorophenyl)-2-tert.-butylaminoethanol-hydrochloride (C-78) were studied in comparison with those of isoproterenol, salbutamol and clorprenaline. C-78 was found to produce a bronchodilating effect 2--10 times stronger and considerably weaker than clorprenaline and isoproterenol, respectively. However, the bronchodilating effect of C-78 was sustained more than 10 times as long as those of isoproterenol and sulbutamol and, especially on oral administration, it was much more potent. The bronchodilating effect of C-78 seems to be due to excitation of the adrenergic beta-receptor, and was antagonized by propranolol. The positive chronotropic and inotropic effects of C-78 on an isolated atrial preparation were less than 1/1000 as potent as those of isoproterenol. C-78 also decreased the tone of smooth muscle, such as the uterus, but its affinity for the bronchial muscle is much higher than for the uterus. C-78 showed strong anti-anaphylactic action and strongly promoted the tracheal ciliary movement. Anitussive effect was also demonstrated, though this was inferior to that of codeine, however, there was no influence on bronchosecretion."}
{"id": "PMID:241357", "title": "Pharmacokinetics of a new beta-adrenoceptor blocking agent, LF 17-895, in man.", "content": "The pharmacokinetics of a new potent beta-adrenoceptor blocking drug, bis-4-(2-hydroxy-3-isopropylamino-propoxy)-2-methyl indole sulphate (LF 17-895), have been studied in 5 volunteers after single oral (10 mg) and intravenous (4 mg) doses in a cross-over design. Following oral administration adsorption was rapid with peak plasma concentrations recorded after 3 h. Following the intravenous dose a biphasic decline of the plasma level curve was observed. The half-life of plasma elimination during beta-phase was 4.6 +/- 0.7 (p.o.) and 4.7 +/- 0.3 (i.v.) h, respectively. Absorption of the drug was 88.3 +/- 9.6% comparing the areas under the curve. 28.4 +/- 2.2% of the dose given i.v. was excreted in urine unchanged. When the pharmacokinetic data obtained with LF 17-895 were compared with those of pindolol, which differs only in lacking one methyl group in position 2 at the indole ring, only minor differences were seen: absorption of pindolol as well as plasma elimination were slightly faster.", "contents": "Pharmacokinetics of a new beta-adrenoceptor blocking agent, LF 17-895, in man. The pharmacokinetics of a new potent beta-adrenoceptor blocking drug, bis-4-(2-hydroxy-3-isopropylamino-propoxy)-2-methyl indole sulphate (LF 17-895), have been studied in 5 volunteers after single oral (10 mg) and intravenous (4 mg) doses in a cross-over design. Following oral administration adsorption was rapid with peak plasma concentrations recorded after 3 h. Following the intravenous dose a biphasic decline of the plasma level curve was observed. The half-life of plasma elimination during beta-phase was 4.6 +/- 0.7 (p.o.) and 4.7 +/- 0.3 (i.v.) h, respectively. Absorption of the drug was 88.3 +/- 9.6% comparing the areas under the curve. 28.4 +/- 2.2% of the dose given i.v. was excreted in urine unchanged. When the pharmacokinetic data obtained with LF 17-895 were compared with those of pindolol, which differs only in lacking one methyl group in position 2 at the indole ring, only minor differences were seen: absorption of pindolol as well as plasma elimination were slightly faster."}
{"id": "PMID:241358", "title": "[Possibilities of detecting and differentiating central nervous effects of drugs in animal experiments with special consideration of behavioral-pharmacologic methods].", "content": "Animal experimental methods suitable for the assessment of actions of drugs of the central nervous system are described with special reference to behavioral actions. The value of those methods for the prediction of central nervous actions of drugs in man are discussed.", "contents": "[Possibilities of detecting and differentiating central nervous effects of drugs in animal experiments with special consideration of behavioral-pharmacologic methods]. Animal experimental methods suitable for the assessment of actions of drugs of the central nervous system are described with special reference to behavioral actions. The value of those methods for the prediction of central nervous actions of drugs in man are discussed."}
{"id": "PMID:241360", "title": "Staphylococcal micrococcins. II. Isolation, purification and identification.", "content": "Seven strains belonging to the Micrococcaceae family and excreting substances with antibiotic activity, were grown in submerged cultures on technical scale for isolation, purification and identification of biologically active compounds. Two basic substances were isolated and classified to the micrococcin antibiotics family. The naturally occurring mixture of micrococcin M1 and M3 was called micrococcin M. This antibiotic has the formula C48H50O11N12S6 and a molecular weight of about 1160, melting point 221--224 degrees C, and optical rotation [a]20/D = + 66.6. Other antibiotically active substances produced by seven investigated strains were identified as micrococcin M or as separate compounds. Comparison with previously described micrococcin and micrococcin P has been made.", "contents": "Staphylococcal micrococcins. II. Isolation, purification and identification. Seven strains belonging to the Micrococcaceae family and excreting substances with antibiotic activity, were grown in submerged cultures on technical scale for isolation, purification and identification of biologically active compounds. Two basic substances were isolated and classified to the micrococcin antibiotics family. The naturally occurring mixture of micrococcin M1 and M3 was called micrococcin M. This antibiotic has the formula C48H50O11N12S6 and a molecular weight of about 1160, melting point 221--224 degrees C, and optical rotation [a]20/D = + 66.6. Other antibiotically active substances produced by seven investigated strains were identified as micrococcin M or as separate compounds. Comparison with previously described micrococcin and micrococcin P has been made."}
{"id": "PMID:241361", "title": "The action of some triphenylmethane dyes on yeast and erythrocyte membranes.", "content": "The action of a series of triphenylmethane dyes on the membranes of two different cell types, yeast cells and erythrocytes, have been studied. The action of the dyes on yeast cells resembles the action of other positively charged bactericides. The sequence of the activity in the dye series is completely different for yeast cells and erythrocytes. Pararosaniline and crystal violet are much more active than malachite green and brilliant green on yeast cells, whereas the reverse sequence of activities applies in erythrocytes. The carbinol form of the dyes plays an important role as regards dye interaction with erythrocytes. Transition of the dye into the carbinol form is in water extremely slow, but is greatly accelerated in the presence of an organic phase, at least for malachite green and brilliant green, but not for crystal violet and pararosaniline. This explains the different action of the two categories of dyes on erythrocytes. Experiments with pure carbinol also support the hypothesis.", "contents": "The action of some triphenylmethane dyes on yeast and erythrocyte membranes. The action of a series of triphenylmethane dyes on the membranes of two different cell types, yeast cells and erythrocytes, have been studied. The action of the dyes on yeast cells resembles the action of other positively charged bactericides. The sequence of the activity in the dye series is completely different for yeast cells and erythrocytes. Pararosaniline and crystal violet are much more active than malachite green and brilliant green on yeast cells, whereas the reverse sequence of activities applies in erythrocytes. The carbinol form of the dyes plays an important role as regards dye interaction with erythrocytes. Transition of the dye into the carbinol form is in water extremely slow, but is greatly accelerated in the presence of an organic phase, at least for malachite green and brilliant green, but not for crystal violet and pararosaniline. This explains the different action of the two categories of dyes on erythrocytes. Experiments with pure carbinol also support the hypothesis."}
{"id": "PMID:241362", "title": "[Development of an oral retard preparation of verapamil and absorption study in the anesthetized dog].", "content": "1. An oral retard preparation of verapamil (Isoptin retard) is described. The sustained release of the active compound from verapamil retard is obtained by mixing and pressing verapamil hydrochloride with sodium alginate. The proportion of active compound and physiologically indifferent additive may range between 1:1 and 1:2. 2. The determination of the in vitro release according to the half-change method shows that verapamil is completely released from the retard preparation only after 6 to 7 h; with conventional drag\u00e9es more than 90% of the compound is dissolved already after 10 min. 3. In artificial gastric and intestinal juice (pH 1.4 and 7.5) similar times of release are found. 4. The in vitro results are supported by tests on the intestinal absorption in the anesthetized dog. In a ligated duodenum section verapamil is, 3 to 8 h after application, markedly more slowly released and absorbed from the retard preparation than from conventional drag\u00e9es.", "contents": "[Development of an oral retard preparation of verapamil and absorption study in the anesthetized dog]. 1. An oral retard preparation of verapamil (Isoptin retard) is described. The sustained release of the active compound from verapamil retard is obtained by mixing and pressing verapamil hydrochloride with sodium alginate. The proportion of active compound and physiologically indifferent additive may range between 1:1 and 1:2. 2. The determination of the in vitro release according to the half-change method shows that verapamil is completely released from the retard preparation only after 6 to 7 h; with conventional drag\u00e9es more than 90% of the compound is dissolved already after 10 min. 3. In artificial gastric and intestinal juice (pH 1.4 and 7.5) similar times of release are found. 4. The in vitro results are supported by tests on the intestinal absorption in the anesthetized dog. In a ligated duodenum section verapamil is, 3 to 8 h after application, markedly more slowly released and absorbed from the retard preparation than from conventional drag\u00e9es."}
{"id": "PMID:241363", "title": "Drug effects on myocardial 45Ca uptake in conscious rats.", "content": "The myocardial content of 45Ca++ in conscious rats is increased by single s.c. injections of sympathomimetics. A dose dependent inhibition of this effect is achieved by simultaneous administration of calcium antagonists or beta-receptor blocking agents. The myocardial 45Ca++ content of conscious rats is increased by i.v. administration of dibutyrylcycloadenosinemonophosphate (DBcAMP). The effect of the cyclic nucleotide is suppressed only by a calcium antagonist but not by a beta-receptor blocker. The following conclusions may be drawn: 1. Calcium antagonists and beta-sympatholytics have different sites of action in the heart. 2. The lack of DBcAMP-antagonism of the beta-sympatholytics permits a simple discrimination between both types of substances. After pretreatment with sympathomimetics for 7 days (0.3 mg/kg isoprenaline s.c.), neither high doses of isoprenaline nor doses of DBcAMP and aminophylline increased the myocardial 45Ca content in rats. This effect only lasted briefly (for about two weeks); the site of its action is so far unknown.", "contents": "Drug effects on myocardial 45Ca uptake in conscious rats. The myocardial content of 45Ca++ in conscious rats is increased by single s.c. injections of sympathomimetics. A dose dependent inhibition of this effect is achieved by simultaneous administration of calcium antagonists or beta-receptor blocking agents. The myocardial 45Ca++ content of conscious rats is increased by i.v. administration of dibutyrylcycloadenosinemonophosphate (DBcAMP). The effect of the cyclic nucleotide is suppressed only by a calcium antagonist but not by a beta-receptor blocker. The following conclusions may be drawn: 1. Calcium antagonists and beta-sympatholytics have different sites of action in the heart. 2. The lack of DBcAMP-antagonism of the beta-sympatholytics permits a simple discrimination between both types of substances. After pretreatment with sympathomimetics for 7 days (0.3 mg/kg isoprenaline s.c.), neither high doses of isoprenaline nor doses of DBcAMP and aminophylline increased the myocardial 45Ca content in rats. This effect only lasted briefly (for about two weeks); the site of its action is so far unknown."}
{"id": "PMID:241364", "title": "Sedative-hypnotic properties of a new benzodiazepine in comparison with flurazepam. Pharmacological and clinical findings.", "content": "The sedative-hypnotic effects of a new benzodiazepine, 1-(2-hydroxyethyl)-3-hydroxy-7-chloro-1,3-dihydro-5-(o-fluorophenyl)-2H-1,4-benzodiazepin-2-one (SAS 643), were compared with those of flurazepam in mice and rats as well as in a double-blind clinical trial. It was found that SAS 643 has a potency 2--4 times greater than that of flurazepam while it is about one half less toxic than the latter drug. The results of the clinical trial confirm the greater activity of SAS 643 and indicate that the new benzodiazepine causes a significantly less amount of hangover than flurazepam.", "contents": "Sedative-hypnotic properties of a new benzodiazepine in comparison with flurazepam. Pharmacological and clinical findings. The sedative-hypnotic effects of a new benzodiazepine, 1-(2-hydroxyethyl)-3-hydroxy-7-chloro-1,3-dihydro-5-(o-fluorophenyl)-2H-1,4-benzodiazepin-2-one (SAS 643), were compared with those of flurazepam in mice and rats as well as in a double-blind clinical trial. It was found that SAS 643 has a potency 2--4 times greater than that of flurazepam while it is about one half less toxic than the latter drug. The results of the clinical trial confirm the greater activity of SAS 643 and indicate that the new benzodiazepine causes a significantly less amount of hangover than flurazepam."}
{"id": "PMID:241365", "title": "[Comparison of the haemodynamic effects in man of the beta-adrenergic blocking substances K\u00f6 1366 and practolol (author's transl)].", "content": "In 21 healthy male persons haemodynamic changes (heart rate, end-diastolic pulmonary artery pressure, training condition of heart, a so-called index of heart sufficiency and arterial blood pressure) at rest and during dynamic exercise were compared respectively before and after i.v. injection of 0.0375 mg/kg of the beta-adrenergic blocking drug K+5Ao 1366 [O-(2-hydroxy-3-(tert. butylamino)-propoxy)-benzonitril-hydrochloride], of 0.3 mg/kg practolol [4-(2-hydroxy-3-isopropylaminopropoxy)-acetanilide] and a placebo. According to the analysed parameters K\u00f6 1366 has an essentially better beta-adrenergic blocking potency than practolol. Neither of the two substances has a negative inotropic effect or influences the arterial blood pressure.", "contents": "[Comparison of the haemodynamic effects in man of the beta-adrenergic blocking substances K\u00f6 1366 and practolol (author's transl)]. In 21 healthy male persons haemodynamic changes (heart rate, end-diastolic pulmonary artery pressure, training condition of heart, a so-called index of heart sufficiency and arterial blood pressure) at rest and during dynamic exercise were compared respectively before and after i.v. injection of 0.0375 mg/kg of the beta-adrenergic blocking drug K+5Ao 1366 [O-(2-hydroxy-3-(tert. butylamino)-propoxy)-benzonitril-hydrochloride], of 0.3 mg/kg practolol [4-(2-hydroxy-3-isopropylaminopropoxy)-acetanilide] and a placebo. According to the analysed parameters K\u00f6 1366 has an essentially better beta-adrenergic blocking potency than practolol. Neither of the two substances has a negative inotropic effect or influences the arterial blood pressure."}
{"id": "PMID:241366", "title": "The effect of diazepam, flunitrazepam and droperidol with an analgesic on blood pressure and heart rate in man.", "content": "The effects of i.v. diazepam (0.3 mg/kg), droperidol (5 mg) and a new benzodiazepine, 5-(a-fluorophenyl)-1,3-dihydro-1-methyl-7-nitro-2H-1,4-benzodiazepin-2-one (flunitrazepam, Ro 5-4200) (0.03 mg/kg) on blood pressure and heart rate was studied in 62 healthy volunteer students. Observations were made after each drug alone, after diazepam and flunitrazepam each combined with pethidine (1 mg/kg), and after droperidol combined with fentanyl (0.2 mg). The doses of the benzodiazepines were halved in those subjects given pethidine but the dose of droperidol was the same with and without fentanyl. The blood pressure was measured by auscultation and the heart rate by counting the radial pulse. The systolic and diastolic blood pressure was regularly decreased by not more than 20 and 11 mmHg, respectively. Changes in the heart rate were slight. Flunitrazepam did not have greater effects than diazepam or droperidol through the combination of flunitrazepam and pethidine seemed to induce a greater fall in systolic blood pressure than did the combination of diazepam and pethidine. None of the changes observed was clinically significant.", "contents": "The effect of diazepam, flunitrazepam and droperidol with an analgesic on blood pressure and heart rate in man. The effects of i.v. diazepam (0.3 mg/kg), droperidol (5 mg) and a new benzodiazepine, 5-(a-fluorophenyl)-1,3-dihydro-1-methyl-7-nitro-2H-1,4-benzodiazepin-2-one (flunitrazepam, Ro 5-4200) (0.03 mg/kg) on blood pressure and heart rate was studied in 62 healthy volunteer students. Observations were made after each drug alone, after diazepam and flunitrazepam each combined with pethidine (1 mg/kg), and after droperidol combined with fentanyl (0.2 mg). The doses of the benzodiazepines were halved in those subjects given pethidine but the dose of droperidol was the same with and without fentanyl. The blood pressure was measured by auscultation and the heart rate by counting the radial pulse. The systolic and diastolic blood pressure was regularly decreased by not more than 20 and 11 mmHg, respectively. Changes in the heart rate were slight. Flunitrazepam did not have greater effects than diazepam or droperidol through the combination of flunitrazepam and pethidine seemed to induce a greater fall in systolic blood pressure than did the combination of diazepam and pethidine. None of the changes observed was clinically significant."}
{"id": "PMID:241370", "title": "Phospholipase A and lysophospholipase activity of the epidermis.", "content": "Phospholipase A and lysophospholipase activities have been demonstrated in cow snout epidermis. The phospholipase A activity was dependent on Ca2+ ions and the pH for optimum activity was between 6-1 and 7-4.", "contents": "Phospholipase A and lysophospholipase activity of the epidermis. Phospholipase A and lysophospholipase activities have been demonstrated in cow snout epidermis. The phospholipase A activity was dependent on Ca2+ ions and the pH for optimum activity was between 6-1 and 7-4."}
{"id": "PMID:241371", "title": "Use of propranolol in dysfunctional labour.", "content": "Labour pains associated with fear and anxiety increase the blood level of catecholamines. This in turn causes dysfunctional labour due to the weak uterine contractions which follow stimulation of uterine adrenergic beta receptors. Intravenous propranolol was administered to ten primigravidae with typical dysfunctional labour. This was shortly followed by normal uterine activity and delivery without any significant maternal or fetal complications. To the best of our knowledge this is the first attempt to treat dysfunctional labour by the intravenous administration of a beta-blocking agent, and our preliminary results are encouraging.", "contents": "Use of propranolol in dysfunctional labour. Labour pains associated with fear and anxiety increase the blood level of catecholamines. This in turn causes dysfunctional labour due to the weak uterine contractions which follow stimulation of uterine adrenergic beta receptors. Intravenous propranolol was administered to ten primigravidae with typical dysfunctional labour. This was shortly followed by normal uterine activity and delivery without any significant maternal or fetal complications. To the best of our knowledge this is the first attempt to treat dysfunctional labour by the intravenous administration of a beta-blocking agent, and our preliminary results are encouraging."}
{"id": "PMID:241372", "title": "Localization of the structural change induced in tRNA fMET (Escherichia coli) by acidic pH.", "content": "We have compared the molecular mechanism of thermal unfolding for native tRNA fMet (Escherichia coli) and the denatured species produced by annealing at pH 4.3. Relaxation kinetic measurements reveal that the transitions assigned to melting of TphiC, anticodon, and acceptor stem helices at neutral pH remain essentially unaltered at pH 4.3, but the transition corresponding to coupled melting of tertiary structure and dihydrouridine helix is greatly affected. The Tm of this region is more than 20 degrees higher at pH 4.3 and it has a larger enthalpy formation than in the native state. The transition dynamics are also considerably changed. In contrast to the native structure, tRNA fMet1 and tRNA fMet3 have similar tertiary structure stabilities at pH 4.3. We conclude that the structural difference between native and acid-denatured forms is localized in the tertiary structure-dihydrouridine helix cooperative interaction region of the molecule.", "contents": "Localization of the structural change induced in tRNA fMET (Escherichia coli) by acidic pH. We have compared the molecular mechanism of thermal unfolding for native tRNA fMet (Escherichia coli) and the denatured species produced by annealing at pH 4.3. Relaxation kinetic measurements reveal that the transitions assigned to melting of TphiC, anticodon, and acceptor stem helices at neutral pH remain essentially unaltered at pH 4.3, but the transition corresponding to coupled melting of tertiary structure and dihydrouridine helix is greatly affected. The Tm of this region is more than 20 degrees higher at pH 4.3 and it has a larger enthalpy formation than in the native state. The transition dynamics are also considerably changed. In contrast to the native structure, tRNA fMet1 and tRNA fMet3 have similar tertiary structure stabilities at pH 4.3. We conclude that the structural difference between native and acid-denatured forms is localized in the tertiary structure-dihydrouridine helix cooperative interaction region of the molecule."}
{"id": "PMID:241373", "title": "Determination of secondary structure in rabbit globin messenger RNA by thermal denaturation.", "content": "The secondary structure of highly purified globin messenger RNA has been investigated by alkaline hydrolysis, nuclease digestion, and thermal denaturation. The thermal denaturation properties of globin messenger have been compared to poly(U), poly (A), and a synthetic random sequence RNA copolymer. From these studies it is concluded that globin mRNA contains considerable secondary structure and that the amount of helical structure is greater than that which occurs with a random sequence polyribonucleotide. Globin mRNA contains, by comparison to the secondary structures of native DNA, tRNAs, or 18S rRNA, helices with involve 55-62% of the bases or 58-68% if a correction is made for the 3'-terminal poly(A) segment. The helices of globin mRNA appear to be unique as differences in the NaCl stabilization of this RNA have been noted when compared to other naturally ooccurring and synthetic RNAs. Comparison of the hyperchromicity maxima, obtained at 260 and 280 nm for globin mRNA and 18S rRNA, indicates that the helices of the two RNAs contain similar numbers of G-C base pairs. Differential analysis of NaCl stabilization curves indicate three discrete thermally denaturable helix types in globin mRNA.", "contents": "Determination of secondary structure in rabbit globin messenger RNA by thermal denaturation. The secondary structure of highly purified globin messenger RNA has been investigated by alkaline hydrolysis, nuclease digestion, and thermal denaturation. The thermal denaturation properties of globin messenger have been compared to poly(U), poly (A), and a synthetic random sequence RNA copolymer. From these studies it is concluded that globin mRNA contains considerable secondary structure and that the amount of helical structure is greater than that which occurs with a random sequence polyribonucleotide. Globin mRNA contains, by comparison to the secondary structures of native DNA, tRNAs, or 18S rRNA, helices with involve 55-62% of the bases or 58-68% if a correction is made for the 3'-terminal poly(A) segment. The helices of globin mRNA appear to be unique as differences in the NaCl stabilization of this RNA have been noted when compared to other naturally ooccurring and synthetic RNAs. Comparison of the hyperchromicity maxima, obtained at 260 and 280 nm for globin mRNA and 18S rRNA, indicates that the helices of the two RNAs contain similar numbers of G-C base pairs. Differential analysis of NaCl stabilization curves indicate three discrete thermally denaturable helix types in globin mRNA."}
{"id": "PMID:241374", "title": "DNA synthesis in isolated HeLa cell nuclei. Optimalization of the system and characterization of the product.", "content": "DNA replication in isolated nuclei from synchronized HeLa cells has been studied in an effort to optimalize the system and characterize the product. The synthesis was highly dependent on the four deoxyribonucleoside triphosphates, ATP, and Mg2+. Optimum pH was about 7.8. The system was further stimulated by monovalent ions with NH4Cl and  Tris-HCl (each 65 mM) being the most effective. The four ribonucleoside triphosphates and glycerol gave a slight but very reproducible and additive stimulation. Low concentrations of spermine and spermidine (0.2-1.5 X 10(-4) M) were also slightly stimulatory (10-15%) whereas higher concentrations were inhibitory. The reaction product was DNase sensitive, and banded at 1.699 g/ml in neutral CsCl together with bulk HeLa nuclear DNA. When studied by neutral CsCl and alkaline Cs2SO4 gradients, the incorporation of [3H]TTP was mainly (more than 85%) due to further elongation of strands initiated in vivo as evidenced by BrdUrd labeling.", "contents": "DNA synthesis in isolated HeLa cell nuclei. Optimalization of the system and characterization of the product. DNA replication in isolated nuclei from synchronized HeLa cells has been studied in an effort to optimalize the system and characterize the product. The synthesis was highly dependent on the four deoxyribonucleoside triphosphates, ATP, and Mg2+. Optimum pH was about 7.8. The system was further stimulated by monovalent ions with NH4Cl and  Tris-HCl (each 65 mM) being the most effective. The four ribonucleoside triphosphates and glycerol gave a slight but very reproducible and additive stimulation. Low concentrations of spermine and spermidine (0.2-1.5 X 10(-4) M) were also slightly stimulatory (10-15%) whereas higher concentrations were inhibitory. The reaction product was DNase sensitive, and banded at 1.699 g/ml in neutral CsCl together with bulk HeLa nuclear DNA. When studied by neutral CsCl and alkaline Cs2SO4 gradients, the incorporation of [3H]TTP was mainly (more than 85%) due to further elongation of strands initiated in vivo as evidenced by BrdUrd labeling."}
{"id": "PMID:241375", "title": "DNA synthesis in isolated HeLa cell nuclei. Evidence for in vitro initiation of synthesis of small pieces of DNA and their subsequent ligation.", "content": "Optimum conditions for a DNA synthesizing system based on isolated nuclei have been described (Krokan, H., Bjorklid, E., and Prydz, H. (1975), Biochemistry, preceding paper in this issue) [3H]TTP-labeled nascent DNA produced during very short pulses was analyzed by centrifugation in alkaline sucrose gradients. More than 80% of the radioactivity appeared in 2-4S pieces (primary DNA pieces). It would therefore seem that the synthesis of DNA is discontinuous both in the 5' leads to 3' and in the 3' leads to 5' directions. The size of the primary DNA pieces increases from 2-4 S up to 14 S with increasing pulse length. Evidence is presented that this increase is not caused by ligation between 2-4S primary pieces. Pulse-chase experiments showed that in this nuclear system primary pieces were ligated to a product generally larger than 30 S. Evidence is also given for the initiation of primary DNA pieces in vitro.", "contents": "DNA synthesis in isolated HeLa cell nuclei. Evidence for in vitro initiation of synthesis of small pieces of DNA and their subsequent ligation. Optimum conditions for a DNA synthesizing system based on isolated nuclei have been described (Krokan, H., Bjorklid, E., and Prydz, H. (1975), Biochemistry, preceding paper in this issue) [3H]TTP-labeled nascent DNA produced during very short pulses was analyzed by centrifugation in alkaline sucrose gradients. More than 80% of the radioactivity appeared in 2-4S pieces (primary DNA pieces). It would therefore seem that the synthesis of DNA is discontinuous both in the 5' leads to 3' and in the 3' leads to 5' directions. The size of the primary DNA pieces increases from 2-4 S up to 14 S with increasing pulse length. Evidence is presented that this increase is not caused by ligation between 2-4S primary pieces. Pulse-chase experiments showed that in this nuclear system primary pieces were ligated to a product generally larger than 30 S. Evidence is also given for the initiation of primary DNA pieces in vitro."}
{"id": "PMID:241376", "title": "Enzymatic activity of the second component of complement.", "content": "Isolated C2 and C2i preparations were able to hydrolyze a number of synthetic esters containing basic amino acids, among which N-alpha-acetylglycyl-L-lysine methyl ester (AcGlyLysOMe) was most susceptible. The cleaving activity was a property of the C2 molecule, since it correlated with the presence of C2 on analyses of C2 preparations by ultracentrifugation in sucrose gradients, filtration through Sephadex G-200 columns, and on electrophoresis in acrylamide gels. Furthermore, acrylamide gel electrophoretic studies showed a shift in hydrolytic activity from the position occupied by C2 to that characteristic of C2i after incubation of C2 with C1s. The action was enzymatically mediated as evidenced by a bell-shaped pH activity curve, a linear dependence on C2 concentration, and the presence of Michaelis-Menten kinetics. The Michaelis constant for cleavage of AcGlyLysOMe by C2 was 1.8 X 10(-2) mol. Cleavage of C2 by C1s increased C2 enzymatic activity, yet chemical oxidation of the molecule, although enhancing hemolytic acitivity, failed to increase C2 hydrolytic activity. The observed enzymatic activity of C2 was found to be relevant to the function of C2 in the C42 complex, since AcGlyLysOMe competitively inhibited the C42 mediated cleavage of C3 in free solution and the C42 dependent binding of C3 to cells.", "contents": "Enzymatic activity of the second component of complement. Isolated C2 and C2i preparations were able to hydrolyze a number of synthetic esters containing basic amino acids, among which N-alpha-acetylglycyl-L-lysine methyl ester (AcGlyLysOMe) was most susceptible. The cleaving activity was a property of the C2 molecule, since it correlated with the presence of C2 on analyses of C2 preparations by ultracentrifugation in sucrose gradients, filtration through Sephadex G-200 columns, and on electrophoresis in acrylamide gels. Furthermore, acrylamide gel electrophoretic studies showed a shift in hydrolytic activity from the position occupied by C2 to that characteristic of C2i after incubation of C2 with C1s. The action was enzymatically mediated as evidenced by a bell-shaped pH activity curve, a linear dependence on C2 concentration, and the presence of Michaelis-Menten kinetics. The Michaelis constant for cleavage of AcGlyLysOMe by C2 was 1.8 X 10(-2) mol. Cleavage of C2 by C1s increased C2 enzymatic activity, yet chemical oxidation of the molecule, although enhancing hemolytic acitivity, failed to increase C2 hydrolytic activity. The observed enzymatic activity of C2 was found to be relevant to the function of C2 in the C42 complex, since AcGlyLysOMe competitively inhibited the C42 mediated cleavage of C3 in free solution and the C42 dependent binding of C3 to cells."}
{"id": "PMID:241377", "title": "Segments of paramyosin formed by cleavage at sites of cysteine residues.", "content": "The helical muscle protein beta-paramyosin of 200,000 was treated by the general method of G. R. Jacobson et al. (1973), J. Biol. Chem. 248, 6583) for cleavage of the polypeptide chain at the site of Cys residues. The protein cleaved into two segments: CCF-1 of 140,000 daltons and CCF-2 of 60,000 daltons. The two segments were separated and some properties were compared. Circular dichroism measurements indicated that CCF-1 was completely helical and that CCF-2 was 85% in the alpha-helical form. The molecular size, resistance to pepsin digestion, stability to heat and urea, and solubility of CCF-1 were all similar to corresponding properties of a pepsin-resistant segment PPC-1 described earlier (Cowgill, R. W. (1972), Biochemistry 11, 4532). By contrast, the properties of CCF-2 were distinctly different. It was concluded that the CCF-1 segment, like the PPC-1 segment, arose from the N-terminal two-thirds of the paramyosin molecule. The CCF-2 segment from the C-terminal one-third of paramyosin had limited solubility at neutral pH that matched the low solubility of paramyosin. It was concluded that the CCF-2 region is responsible for the self-aggregating tendency of paramyosin at neutral pH and low ionic strength.", "contents": "Segments of paramyosin formed by cleavage at sites of cysteine residues. The helical muscle protein beta-paramyosin of 200,000 was treated by the general method of G. R. Jacobson et al. (1973), J. Biol. Chem. 248, 6583) for cleavage of the polypeptide chain at the site of Cys residues. The protein cleaved into two segments: CCF-1 of 140,000 daltons and CCF-2 of 60,000 daltons. The two segments were separated and some properties were compared. Circular dichroism measurements indicated that CCF-1 was completely helical and that CCF-2 was 85% in the alpha-helical form. The molecular size, resistance to pepsin digestion, stability to heat and urea, and solubility of CCF-1 were all similar to corresponding properties of a pepsin-resistant segment PPC-1 described earlier (Cowgill, R. W. (1972), Biochemistry 11, 4532). By contrast, the properties of CCF-2 were distinctly different. It was concluded that the CCF-1 segment, like the PPC-1 segment, arose from the N-terminal two-thirds of the paramyosin molecule. The CCF-2 segment from the C-terminal one-third of paramyosin had limited solubility at neutral pH that matched the low solubility of paramyosin. It was concluded that the CCF-2 region is responsible for the self-aggregating tendency of paramyosin at neutral pH and low ionic strength."}
{"id": "PMID:241378", "title": "Gel filtration studies of oxyhemerythrin. I. Effects of pH on the association-dissociation equilibria.", "content": "The pH dependency of the dissociation of oxyhemerythrin has been studied by frontal gel chromatography on Sephadex G-75. The extent of dissociation is markedly pH dependent increasing below pH 6.0 and above pH 8.8. In addition, the nature of the dissociation reaction undergoes dramatic change with pH. Below pH 6.4 the rate of equilibration between species is slow relative to their time of passage through the column and they are thus resolved on chromatography. Above pH 6.6 the rate of equilibration is rapid and the various forms of hemerythrin are not resolved on migration through the column. Below pH 7.4 the dissociation is an all-or-none process with no detectable intermediates. Above pH 8.0 several intermediate species can be detected. Values for Keq and deltaG degrees are presented for various forms of oxyhemerythrin at the several pH's studied.", "contents": "Gel filtration studies of oxyhemerythrin. I. Effects of pH on the association-dissociation equilibria. The pH dependency of the dissociation of oxyhemerythrin has been studied by frontal gel chromatography on Sephadex G-75. The extent of dissociation is markedly pH dependent increasing below pH 6.0 and above pH 8.8. In addition, the nature of the dissociation reaction undergoes dramatic change with pH. Below pH 6.4 the rate of equilibration between species is slow relative to their time of passage through the column and they are thus resolved on chromatography. Above pH 6.6 the rate of equilibration is rapid and the various forms of hemerythrin are not resolved on migration through the column. Below pH 7.4 the dissociation is an all-or-none process with no detectable intermediates. Above pH 8.0 several intermediate species can be detected. Values for Keq and deltaG degrees are presented for various forms of oxyhemerythrin at the several pH's studied."}
{"id": "PMID:241379", "title": "Gel filtration studies on oxyhemerythrin. II. Effect of temperature and ionic strength on the association-dissociation equilibria.", "content": "The effects of temperature and ionic strength on the association of oxyhemerythrin have been studied. deltaH degrees and deltaS degrees for association at pH 7.0 are -2.6 kcal and +16.5 eu per mol of monomer. These values suggest that solvent adjacent to the surface of the protein undergoes rearrangement on association. Increasing ionic strength is observed to promote dissociation while decreasing the rate of attainment of equilibrium between monomers and octamers. Qualitatively similar results are observed on lowering the pH from 7.0 to 4.8, thereby linking the effects of increasing ionic strength to those of protonation of specific amino acid residues at the subunit contacts of hemerythrin. The apparent enthalpy of ionization of the amino acid residue controlling dissociation at acidic pH was found to be -1.9 to +2.1 kcal/mol. These values are consistent with a carboxyl group.", "contents": "Gel filtration studies on oxyhemerythrin. II. Effect of temperature and ionic strength on the association-dissociation equilibria. The effects of temperature and ionic strength on the association of oxyhemerythrin have been studied. deltaH degrees and deltaS degrees for association at pH 7.0 are -2.6 kcal and +16.5 eu per mol of monomer. These values suggest that solvent adjacent to the surface of the protein undergoes rearrangement on association. Increasing ionic strength is observed to promote dissociation while decreasing the rate of attainment of equilibrium between monomers and octamers. Qualitatively similar results are observed on lowering the pH from 7.0 to 4.8, thereby linking the effects of increasing ionic strength to those of protonation of specific amino acid residues at the subunit contacts of hemerythrin. The apparent enthalpy of ionization of the amino acid residue controlling dissociation at acidic pH was found to be -1.9 to +2.1 kcal/mol. These values are consistent with a carboxyl group."}
{"id": "PMID:241380", "title": "Pyridoxal 5'-phosphate and analogs as probes of coenzyme-protein interaction in Baccillus alvei tryptophanase.", "content": "Trytophanase from Bacillus alvei was resolved from its coenzyme, pyridoxal phosphate, by treatment with cysteine followed by column chromatography. Spectrophotometric titration of apoenzyme with pyridoxal-P showed 1 mol of pyridoxal-P bound per 52,000 g of enzyme. Kinetic analysis of coenzyme binding showed hyperbolic activation curves with a Km of 1.6 muM. Pyridoxal-P was used as a natural active site probe in spectrophotometric studies to distinguish differences in the active center of holotryptophanase and reconstituted enzyme that were not apparent by other techniques. The pKa for holotryptophanase is 7.9 while the pKa for reconstituted apoenzyme is 8.4. Apotryptophanase binds 2-nor, 2'-methyl, 2'-hydroxy, 6-methyl, and N-oxide pyridoxal-P to form analog enzymes distinguishable on the basis of absorption spectra and relative activity in catalyzing both the alpha, beta-elimination and beta-replacement reactions of tryptophanase. Apoenzyme also binds pyridoxal but pyridoxal analog enzyme is not active.", "contents": "Pyridoxal 5'-phosphate and analogs as probes of coenzyme-protein interaction in Baccillus alvei tryptophanase. Trytophanase from Bacillus alvei was resolved from its coenzyme, pyridoxal phosphate, by treatment with cysteine followed by column chromatography. Spectrophotometric titration of apoenzyme with pyridoxal-P showed 1 mol of pyridoxal-P bound per 52,000 g of enzyme. Kinetic analysis of coenzyme binding showed hyperbolic activation curves with a Km of 1.6 muM. Pyridoxal-P was used as a natural active site probe in spectrophotometric studies to distinguish differences in the active center of holotryptophanase and reconstituted enzyme that were not apparent by other techniques. The pKa for holotryptophanase is 7.9 while the pKa for reconstituted apoenzyme is 8.4. Apotryptophanase binds 2-nor, 2'-methyl, 2'-hydroxy, 6-methyl, and N-oxide pyridoxal-P to form analog enzymes distinguishable on the basis of absorption spectra and relative activity in catalyzing both the alpha, beta-elimination and beta-replacement reactions of tryptophanase. Apoenzyme also binds pyridoxal but pyridoxal analog enzyme is not active."}
{"id": "PMID:241381", "title": "Structural role of pyridoxal 5'-phosphate, pyridoxal 5'-phosphate analogs, and other agents in the association of subunits of Bacillus alvei apotryptophanase.", "content": "Bacillus alvei apotryptophanase readily dissociates at low protein concentration and sediments at 5.7 S (dimer) in 0.01 M potassium phosphate (pH 7.8) from 9 to 33 degrees. With temperature held constant at 9 degrees, increasing the potassium, sodium, or ammonium phosphate buffer concentration increases the sedimentation value to 8.0 S. Increasing the monovalent cation concentration alone does not have the effect. Imidazole and pyridoxal compete with phosphate, preventing the effect. Raising the temperature to 26 degrees in the presence of high concentrations of potassium phosphate increases the sedimentation constant to 9.4 S. The addition of pyridoxal-P converts the dimer to a 9.4S tetramer. The conversion is dependent upon coenzyme concentration, temperature, and the nature of monovalent cation present. The Km for pyridoxal-P for the sodium form of the enzyme is more than tenfold greater than the Km for the potassium form of the enzyme. 2'-Methyl, 2'-hydroxyl, 6-methyl, and the N-oxide of pyridoxal-P are active in the association of dimer to tetramer but to differing extents. Analogs altered in the 4'-formyl position are also inactive structurally. Anthranilic acid, a competitive inhibitor of tryptophan, and 8-anilino-1-naphthalenesulfonic acid (ANS), a competitive inhibitor of pyridoxal-P binding, are both active in affecting the dimer to tetramer association but tryptophan is not. The dimer and tetramer are spectrally distinguishable through circular dichroic measurements, fluroescence quenching with pyridoxal-P or pyridoxal, and fluorescence enhancement with ANS. Pyridoxal-P causes the release of ANS from an ANS-apoenzyme complex.", "contents": "Structural role of pyridoxal 5'-phosphate, pyridoxal 5'-phosphate analogs, and other agents in the association of subunits of Bacillus alvei apotryptophanase. Bacillus alvei apotryptophanase readily dissociates at low protein concentration and sediments at 5.7 S (dimer) in 0.01 M potassium phosphate (pH 7.8) from 9 to 33 degrees. With temperature held constant at 9 degrees, increasing the potassium, sodium, or ammonium phosphate buffer concentration increases the sedimentation value to 8.0 S. Increasing the monovalent cation concentration alone does not have the effect. Imidazole and pyridoxal compete with phosphate, preventing the effect. Raising the temperature to 26 degrees in the presence of high concentrations of potassium phosphate increases the sedimentation constant to 9.4 S. The addition of pyridoxal-P converts the dimer to a 9.4S tetramer. The conversion is dependent upon coenzyme concentration, temperature, and the nature of monovalent cation present. The Km for pyridoxal-P for the sodium form of the enzyme is more than tenfold greater than the Km for the potassium form of the enzyme. 2'-Methyl, 2'-hydroxyl, 6-methyl, and the N-oxide of pyridoxal-P are active in the association of dimer to tetramer but to differing extents. Analogs altered in the 4'-formyl position are also inactive structurally. Anthranilic acid, a competitive inhibitor of tryptophan, and 8-anilino-1-naphthalenesulfonic acid (ANS), a competitive inhibitor of pyridoxal-P binding, are both active in affecting the dimer to tetramer association but tryptophan is not. The dimer and tetramer are spectrally distinguishable through circular dichroic measurements, fluroescence quenching with pyridoxal-P or pyridoxal, and fluorescence enhancement with ANS. Pyridoxal-P causes the release of ANS from an ANS-apoenzyme complex."}
{"id": "PMID:241382", "title": "Magnesium-induced self-association of calf brain tubulin. I. Stoichiometry.", "content": "The self-association of calf brain tubulin at pH 7.0 in the presence of magnesium ions has been examined by velocity sedimentation. The schlieren patterns were analyzed by methods described by Gilbert and by Cox. The observed process is best described in terms of a rapidly reversible progressive self-association of the tubulin dimer with identical chain elongation equilibrium constants, k, terminated by a ring-closing step, at degree of polymerization n = 26 +/- 2, with k26 greater than k. The end product of the polymerization reaction has a sedimentation coefficient s20,w0 k2 +/- 2 S. It is hydrodynamically equivalent to a closed ring structure observed in the electron microscope at identical conditions.", "contents": "Magnesium-induced self-association of calf brain tubulin. I. Stoichiometry. The self-association of calf brain tubulin at pH 7.0 in the presence of magnesium ions has been examined by velocity sedimentation. The schlieren patterns were analyzed by methods described by Gilbert and by Cox. The observed process is best described in terms of a rapidly reversible progressive self-association of the tubulin dimer with identical chain elongation equilibrium constants, k, terminated by a ring-closing step, at degree of polymerization n = 26 +/- 2, with k26 greater than k. The end product of the polymerization reaction has a sedimentation coefficient s20,w0 k2 +/- 2 S. It is hydrodynamically equivalent to a closed ring structure observed in the electron microscope at identical conditions."}
{"id": "PMID:241383", "title": "Nonequivalence of the metal binding sites in vanadyl-labeled human serum transferrin.", "content": "Vanadyl ion, VO(IV), has been used as an electron paramagnetic resonance (EPR) spin label to study the metal-binding properties of human serum transferrin in the presence of bicarbonate. Iron-saturated transferrin does not bind the vanadyl ion. Room temperature titrations of apotransferrin with VO(IV) as monitored by EPR indicate the extent of binding to be pH dependent, with a full 0.2 VO(IV) ions per transferrin molecule bound at pH 7.5 and 9, but only about 1.2 VO(IV) ions bound at pH 6. The EPR spectra of frozen solutions with or without 0.1 M NaCUO4 at 77 K show that there are two spectroscopically nonequivalent binding sites (A and B) with a slight difference in binding constants. One site (A site) exhibits essentially constant binding capacity in the pH range 6-9, but the other (B site) becomes less avialable as the pH is reduced below 7. Results with mixed Fe(III)-VO(IV) transferrin complexes suggest that iron shows a slight tendency to bind at the B site over the A site pH 7.5 and 9.0. Only the B site in both vanadyl and iron transferrins is perturbed by the presence of perchlorate.", "contents": "Nonequivalence of the metal binding sites in vanadyl-labeled human serum transferrin. Vanadyl ion, VO(IV), has been used as an electron paramagnetic resonance (EPR) spin label to study the metal-binding properties of human serum transferrin in the presence of bicarbonate. Iron-saturated transferrin does not bind the vanadyl ion. Room temperature titrations of apotransferrin with VO(IV) as monitored by EPR indicate the extent of binding to be pH dependent, with a full 0.2 VO(IV) ions per transferrin molecule bound at pH 7.5 and 9, but only about 1.2 VO(IV) ions bound at pH 6. The EPR spectra of frozen solutions with or without 0.1 M NaCUO4 at 77 K show that there are two spectroscopically nonequivalent binding sites (A and B) with a slight difference in binding constants. One site (A site) exhibits essentially constant binding capacity in the pH range 6-9, but the other (B site) becomes less avialable as the pH is reduced below 7. Results with mixed Fe(III)-VO(IV) transferrin complexes suggest that iron shows a slight tendency to bind at the B site over the A site pH 7.5 and 9.0. Only the B site in both vanadyl and iron transferrins is perturbed by the presence of perchlorate."}
{"id": "PMID:241384", "title": "Heats of carbon monoxide binding by hemoglobin M Iwate.", "content": "The heat of reaction of CO gas with the alpha2Mmetbeta2 and alpha2Mbeta2 species of the alpha-chain mutant hemoglobin M Iwate has been studied in buffers with different heats of ionization of 25degrees and in the absence of organic phosphates. For the alpha2Mmetbeta2deoxy species we find a small Bohr effect (0.12 mol of H+/mol of CO) which is in correspondence with that found in equilibrium studies. The heat of reaction, when corrected for proton reaction with buffer, is -18.4 +/- 0.3 kcal/mol of CO at pH 7.4 At pH 9 the same value is observed within experimental error. This value compares closely with heats of reaction of CO with myoglobin and with van't Hoff determinations of the heat of oxygen binding to isolated hemoglobin alpha and beta chains after correction for the heat of replacement of O2 by CO. Furthermore, an analysis of the differential heat of ligand binding as a function of the extent of reaction indicated that, within experimental error, the heat of reaction with the first beta-chain heme in alpha2Mmetbeta2deoxy is the same as the second. Since the quaternary Tleads to R transition is blocked in this mutant hemoglobin, we compared it with Hb A to estimate the enthalpic component of the allosteric T leads to R transition in Hb A. The heats of reaction with CO(g) and Hb A are -15.7 +/- 0.5 and -20.9 +/- 0.5 kcal/mol at pH 7.4 and 9.0, respectively. In going from the T to the R state we find an enthalpy of transition of 9 +/- 2.5 kcal at pH 7.4 and -12 +/- 2.5 kcal at pH 9.0. From published free energies of transsition we conclude the T leads to R transition is enthalpically controlled at p/ 7.4 but entropically controlled at pH 9.0 A near normal Bohr effect is estimated from heats of reaction of CO with alpha2Mdeoxybeta2deoxy in various buffers. A large than normal heat of reaction (-21.6 +/- 0.5 kcal/mol of CO) is attributed to the abnormal alpha chains in Hb M Iwate.", "contents": "Heats of carbon monoxide binding by hemoglobin M Iwate. The heat of reaction of CO gas with the alpha2Mmetbeta2 and alpha2Mbeta2 species of the alpha-chain mutant hemoglobin M Iwate has been studied in buffers with different heats of ionization of 25degrees and in the absence of organic phosphates. For the alpha2Mmetbeta2deoxy species we find a small Bohr effect (0.12 mol of H+/mol of CO) which is in correspondence with that found in equilibrium studies. The heat of reaction, when corrected for proton reaction with buffer, is -18.4 +/- 0.3 kcal/mol of CO at pH 7.4 At pH 9 the same value is observed within experimental error. This value compares closely with heats of reaction of CO with myoglobin and with van't Hoff determinations of the heat of oxygen binding to isolated hemoglobin alpha and beta chains after correction for the heat of replacement of O2 by CO. Furthermore, an analysis of the differential heat of ligand binding as a function of the extent of reaction indicated that, within experimental error, the heat of reaction with the first beta-chain heme in alpha2Mmetbeta2deoxy is the same as the second. Since the quaternary Tleads to R transition is blocked in this mutant hemoglobin, we compared it with Hb A to estimate the enthalpic component of the allosteric T leads to R transition in Hb A. The heats of reaction with CO(g) and Hb A are -15.7 +/- 0.5 and -20.9 +/- 0.5 kcal/mol at pH 7.4 and 9.0, respectively. In going from the T to the R state we find an enthalpy of transition of 9 +/- 2.5 kcal at pH 7.4 and -12 +/- 2.5 kcal at pH 9.0. From published free energies of transsition we conclude the T leads to R transition is enthalpically controlled at p/ 7.4 but entropically controlled at pH 9.0 A near normal Bohr effect is estimated from heats of reaction of CO with alpha2Mdeoxybeta2deoxy in various buffers. A large than normal heat of reaction (-21.6 +/- 0.5 kcal/mol of CO) is attributed to the abnormal alpha chains in Hb M Iwate."}
{"id": "PMID:241385", "title": "Crystallization and partial characterization of glutamate dehydrogenase from ox liver nuclei.", "content": "Glutamate dehydrogenase have been obtained in crystalline form from purified ox liver nuclear fractions. The enzyme appeared homogeneous, as judged by several electrophoretic techniques at two pH values. A comparative study with the widely known ox liver mitochondrial glutamate dehydrogenase revealed several common features, such as the allosteric effect of the nucleotides ADP and GTP, the activation at high concentrations of the cofactor NAD+, and the existence of a concentration-dependent reversible monomer-polymer(s) equilibrium. However, the two enzymes differed in many other respects. Inorganic phosphate activated nuclear glutamate dehydrogenase to a much greater extent than the mitochondrial enzyme; the substrate NH4+ showed cooperative homotropic interactions only with nuclear glutamate dehydrogenase; kinetic differences were detected with most of the reaction substrates, as well as different rates of oxidative deamination of other L-amino acids, the nuclear enzyme had a higher anodic mobility and a different chromatographic behavior on anionic exchangers. The latter evidence indicates that the glutamate dehydrogenase activity in liver is associated with two proteins which are structurally different, thus confirming the results of a separate immunological study. Preliminary evidence suggests that the enzyme in nuclei is attached to the nuclear envelope, probably the inner membrane, from which it can be solubilized by the addition of salts.", "contents": "Crystallization and partial characterization of glutamate dehydrogenase from ox liver nuclei. Glutamate dehydrogenase have been obtained in crystalline form from purified ox liver nuclear fractions. The enzyme appeared homogeneous, as judged by several electrophoretic techniques at two pH values. A comparative study with the widely known ox liver mitochondrial glutamate dehydrogenase revealed several common features, such as the allosteric effect of the nucleotides ADP and GTP, the activation at high concentrations of the cofactor NAD+, and the existence of a concentration-dependent reversible monomer-polymer(s) equilibrium. However, the two enzymes differed in many other respects. Inorganic phosphate activated nuclear glutamate dehydrogenase to a much greater extent than the mitochondrial enzyme; the substrate NH4+ showed cooperative homotropic interactions only with nuclear glutamate dehydrogenase; kinetic differences were detected with most of the reaction substrates, as well as different rates of oxidative deamination of other L-amino acids, the nuclear enzyme had a higher anodic mobility and a different chromatographic behavior on anionic exchangers. The latter evidence indicates that the glutamate dehydrogenase activity in liver is associated with two proteins which are structurally different, thus confirming the results of a separate immunological study. Preliminary evidence suggests that the enzyme in nuclei is attached to the nuclear envelope, probably the inner membrane, from which it can be solubilized by the addition of salts."}
{"id": "PMID:241386", "title": "Kinetics of sulfate transport by Penicillium notatum. Interactions of sulfate, protons, and calcium.", "content": "The active transport of inorganic sulfate by an ATP sulfurylase-negative strain of Penicillium notatum is promoted by H+ ions and metal ions (divalent metal ions being more effective than monovalent metal ions). Initial velocity studies suggest that H+ and SO4(2-) add to the carrier in an ordered sequence (H+ before SO4(2-)), with H+ at equilibrium with free carrier and carrier-H+ complex. The linear reciprocal plots and replots suggest a 1:1 stoichiometry between H+ and SO4(2-). Ca2+ and other divalent metal ions stimulate sulfate transport markedly in buffered suspensions of low ionic strength. The kinetics of the Ca2+/SO4(2-) interaction suggest that Ca2+ (like H+) adds to the carrier before SO4(2-) and is at equilibrium with free carrier and carrier-Ca2+ complex. The linear reciprocal plots and replots indicate a 1:1 stoichiometry between Ca2+ and SO4(2-). Thus the fully loaded carrier-SO4(2-) -Ca2+ -H+ complex has a net positive charge relative to that of the free carrier, a fact consistent with the chemiosmotic hypothesis of membrane transport. The kinetics of the H+/Ca2+ interaction point to a random A-B (rapid equilibrium), ordered C sequence with A = H+, B = Ca2+, and C = SO4(2-). Selenate (an alternate substrate competitive with sulfate) is an uncompetitive inhibitor with respect to Ca2+, in agreement with the suggested mechanism. Internal charge balance is not accomplished by a stoichiometric coaccumulation of Ca2+ and SO4(2-). Sulfate transport does, however, promote 45Ca2+ uptake. A significant fraction of the added Ca2+ is bound by the mycelial surface. Binding is extremely rapid, but reversible.", "contents": "Kinetics of sulfate transport by Penicillium notatum. Interactions of sulfate, protons, and calcium. The active transport of inorganic sulfate by an ATP sulfurylase-negative strain of Penicillium notatum is promoted by H+ ions and metal ions (divalent metal ions being more effective than monovalent metal ions). Initial velocity studies suggest that H+ and SO4(2-) add to the carrier in an ordered sequence (H+ before SO4(2-)), with H+ at equilibrium with free carrier and carrier-H+ complex. The linear reciprocal plots and replots suggest a 1:1 stoichiometry between H+ and SO4(2-). Ca2+ and other divalent metal ions stimulate sulfate transport markedly in buffered suspensions of low ionic strength. The kinetics of the Ca2+/SO4(2-) interaction suggest that Ca2+ (like H+) adds to the carrier before SO4(2-) and is at equilibrium with free carrier and carrier-Ca2+ complex. The linear reciprocal plots and replots indicate a 1:1 stoichiometry between Ca2+ and SO4(2-). Thus the fully loaded carrier-SO4(2-) -Ca2+ -H+ complex has a net positive charge relative to that of the free carrier, a fact consistent with the chemiosmotic hypothesis of membrane transport. The kinetics of the H+/Ca2+ interaction point to a random A-B (rapid equilibrium), ordered C sequence with A = H+, B = Ca2+, and C = SO4(2-). Selenate (an alternate substrate competitive with sulfate) is an uncompetitive inhibitor with respect to Ca2+, in agreement with the suggested mechanism. Internal charge balance is not accomplished by a stoichiometric coaccumulation of Ca2+ and SO4(2-). Sulfate transport does, however, promote 45Ca2+ uptake. A significant fraction of the added Ca2+ is bound by the mycelial surface. Binding is extremely rapid, but reversible."}
{"id": "PMID:241387", "title": "The kinetics of flavine oxidation--reduction. I. Dismutation in nonaqueous solvent.", "content": "The dismutation reactions of flavines in dimethylformanide have been investigated using the stopped-flow technique under anaerobic conditions. The ionization constants of fully reduced and oxidized tetraacetylriboflavine were measured spectrophotometrically in buffered dimethylformanide. The dismutation equilibrium of the flavine as a function of pH in dimethylformanide was roughly comparable to that reported in water and allowed the estimation of the pKa value of the flavosemiquinone. The dismutation kinetics of tetraacetylriboflavine in unbuffered dimethylformanide were investigated using the fully oxidized and reduced flavines in their neutral form at constant produce of concentrations and varying the reduction degree. The kinetics at very low reduction ratios (less than3%) were triphasic. The kinetic analysis of the initial and simultaneous formation of the anionic and neutral radicals revealed a second-order reaction. The electron transfer between the oxidized and reduced flavines was not directly coupled with prton exchange. The multiphasic time course of the reaction proceeded primarily from differences in the intrinsic rates of the direct and mixed backward dismutation reactions of the two radical species, and finally from a change in the equilibrium conditions resulting from the accumulation of anionic flavohydroquinone. An acidic-basic negative catalytic effect from the neutral flavohydroquinone appeared progressively as the reduction degree was increased. It was complete at reduction ratios higher than 30%, i.e. under conditions where the radical anion could not be observed at any reaction time. Acids with a pKa value lower than the second one of the flavosemiquinone exhibited a similar catalytic effect. These acidic-basic catalytic effects are associated with changes in the ionic state of labile intermediate dimers formed in the forward as well as in the backward direactions of the dismutation reaction. Such a transient complex revealed by the kinetic analysis could be observed directly by absorption spectroscopy in alkaline-buffered dimethylformanide. Its spectral characteristics, as well as the kinetic effects induced by substitution of the benzenoid part of the flavine, can hardly be taken into account by a quinhydrone-like structure for the intermediate dimers at any pH value. The experimental results favored a more specific interaction, possibly of covalent character, involving the benzenoid part of the isoalloxazine ring.", "contents": "The kinetics of flavine oxidation--reduction. I. Dismutation in nonaqueous solvent. The dismutation reactions of flavines in dimethylformanide have been investigated using the stopped-flow technique under anaerobic conditions. The ionization constants of fully reduced and oxidized tetraacetylriboflavine were measured spectrophotometrically in buffered dimethylformanide. The dismutation equilibrium of the flavine as a function of pH in dimethylformanide was roughly comparable to that reported in water and allowed the estimation of the pKa value of the flavosemiquinone. The dismutation kinetics of tetraacetylriboflavine in unbuffered dimethylformanide were investigated using the fully oxidized and reduced flavines in their neutral form at constant produce of concentrations and varying the reduction degree. The kinetics at very low reduction ratios (less than3%) were triphasic. The kinetic analysis of the initial and simultaneous formation of the anionic and neutral radicals revealed a second-order reaction. The electron transfer between the oxidized and reduced flavines was not directly coupled with prton exchange. The multiphasic time course of the reaction proceeded primarily from differences in the intrinsic rates of the direct and mixed backward dismutation reactions of the two radical species, and finally from a change in the equilibrium conditions resulting from the accumulation of anionic flavohydroquinone. An acidic-basic negative catalytic effect from the neutral flavohydroquinone appeared progressively as the reduction degree was increased. It was complete at reduction ratios higher than 30%, i.e. under conditions where the radical anion could not be observed at any reaction time. Acids with a pKa value lower than the second one of the flavosemiquinone exhibited a similar catalytic effect. These acidic-basic catalytic effects are associated with changes in the ionic state of labile intermediate dimers formed in the forward as well as in the backward direactions of the dismutation reaction. Such a transient complex revealed by the kinetic analysis could be observed directly by absorption spectroscopy in alkaline-buffered dimethylformanide. Its spectral characteristics, as well as the kinetic effects induced by substitution of the benzenoid part of the flavine, can hardly be taken into account by a quinhydrone-like structure for the intermediate dimers at any pH value. The experimental results favored a more specific interaction, possibly of covalent character, involving the benzenoid part of the isoalloxazine ring."}
{"id": "PMID:241388", "title": "The kinetics of flavine oxidation-reduction. II. Metal ion interactions.", "content": "The oxidation-reduction reactions of tetraacetylriboflavine in the presence of various metal ions in dimethylformamide have been investigated using the stopped-flow technique under anaerobic conditions. Dismutation kinetics in the presence of redox-inactive dissociated divalent metal ions such as Cd2+, Zn2+, and Fe2+ are typically triphasic. Metal ions act primarily upon an intermediate flavine dimer formed by fast association of flavoquinone and flavohydroquinone, resulting in a parallel formation and neutral and chelated radicals. A competition between metal ions and proton donors, e.g. the neutral flavohydroquinone (FredH3), is observed at the level of this intermediate complex. Small spectral changes occur secondarily as an ill-defined intermediate phase which could correspond to the reorganization of the solvation of radical chelate. The neutral radical is finally chelated at a much slower rate, the yield of total radical formation remaining almost unchanged during this kinetic phase. The oxidation of flavohydroquinone by ferric ions, either dissociated or strongly coordinated within a porphyrin, is complete and proceeds through biphasic kinetics. The first phase (Fred leads to F) is much faster than the second one (F leads to Fox). Dismutation resulting from the transient accumulation of neutral flavosemiquinone competes with the direct oxidation with ferric ions for the completion of the second oxidation step. The relative rate of dismutation is essentially limited by acidic-basic reactions in the absence of an excess of ferrous ion. The kinetic analysis of the direct oxidation reactions favors an outer-sphere mechanism for the electron transfer to the ferric ion, either free or strongly coordinated. The formation of a ferrous radical chelate can result from the dismutation reactions only when the amount of ferric ion initially present is not sufficient for complete oxidation.", "contents": "The kinetics of flavine oxidation-reduction. II. Metal ion interactions. The oxidation-reduction reactions of tetraacetylriboflavine in the presence of various metal ions in dimethylformamide have been investigated using the stopped-flow technique under anaerobic conditions. Dismutation kinetics in the presence of redox-inactive dissociated divalent metal ions such as Cd2+, Zn2+, and Fe2+ are typically triphasic. Metal ions act primarily upon an intermediate flavine dimer formed by fast association of flavoquinone and flavohydroquinone, resulting in a parallel formation and neutral and chelated radicals. A competition between metal ions and proton donors, e.g. the neutral flavohydroquinone (FredH3), is observed at the level of this intermediate complex. Small spectral changes occur secondarily as an ill-defined intermediate phase which could correspond to the reorganization of the solvation of radical chelate. The neutral radical is finally chelated at a much slower rate, the yield of total radical formation remaining almost unchanged during this kinetic phase. The oxidation of flavohydroquinone by ferric ions, either dissociated or strongly coordinated within a porphyrin, is complete and proceeds through biphasic kinetics. The first phase (Fred leads to F) is much faster than the second one (F leads to Fox). Dismutation resulting from the transient accumulation of neutral flavosemiquinone competes with the direct oxidation with ferric ions for the completion of the second oxidation step. The relative rate of dismutation is essentially limited by acidic-basic reactions in the absence of an excess of ferrous ion. The kinetic analysis of the direct oxidation reactions favors an outer-sphere mechanism for the electron transfer to the ferric ion, either free or strongly coordinated. The formation of a ferrous radical chelate can result from the dismutation reactions only when the amount of ferric ion initially present is not sufficient for complete oxidation."}
{"id": "PMID:241389", "title": "An affinity adsorbent containing deoxyguanosine 5'-triphosphate linked to sepharose and its use for large scale preparation of ribonucleotide reductase of Lactobacillus leichmannii.", "content": "P3-(6-(N-Trifluoracetyl)aminohex-1-yl) deoxyguanosine triphosphate has been prepared by the reaction of N-trifluoroacetyl-6-aminohexanol 1-pyrophosphate with the imidazolide of dGMP and has been characterized. This compound and the corresponding free amine, obtained by removal of the protective trigluoroacetyl group, are activators of ribonucleotide reductase of Lactobacillus leichmannii. An affinity adsorbent for the reductase, prepared by reaction of the amine derivative with CNBr-activated Sepharose, contains dGTP covalently attached through the gamma-phosphate via a six-carbon chain to the matrix. The method of synthesis of the dGTP derivative is generally applicable to the synthesis of P3-(omega-aminoalk-1-yl)nucleoside triphosphate esters for the preparation of analogous affinity adsorbents. Ribonucleotide reductase can be rapidly purified to homogeneity, on a large scale, by use of dGTP-Sepharose and conditions for optimum recovery of the enzyme have been determined. The affinity of ribonucleotide reductase and other proteins for dGTP-Sepharose is increased by either raising the ionic strength or lowering the temperature of the eluent. Elution of the enzyme from the adsorbent can be achieved between pH 5.8 and 7.3, whereas at pH 5.3 the reductase is bound extremely tightly and cannot be recovered. Ribonucleotide reductase can be eluted from the adsorbent with dGTP or urea. Elution with urea is carried out at pH 6.3, where the enzyme is stable and maximum recovery is obtained. Affinity chromatography consistently produces ribonucleotide reductase of high specific activity (170-180 units/mg). In the presence of 0.1 to 1.2 M urea or hydroxyurea, the enzyme is inhibited, but allosteric activation is unchanged. No alteration in the structure or function of the reductase was detected when the enzyme was exposed to 2.0 M urea during elution from the affinity adsorbent, but exposure for longer periods causes some inactivation.", "contents": "An affinity adsorbent containing deoxyguanosine 5'-triphosphate linked to sepharose and its use for large scale preparation of ribonucleotide reductase of Lactobacillus leichmannii. P3-(6-(N-Trifluoracetyl)aminohex-1-yl) deoxyguanosine triphosphate has been prepared by the reaction of N-trifluoroacetyl-6-aminohexanol 1-pyrophosphate with the imidazolide of dGMP and has been characterized. This compound and the corresponding free amine, obtained by removal of the protective trigluoroacetyl group, are activators of ribonucleotide reductase of Lactobacillus leichmannii. An affinity adsorbent for the reductase, prepared by reaction of the amine derivative with CNBr-activated Sepharose, contains dGTP covalently attached through the gamma-phosphate via a six-carbon chain to the matrix. The method of synthesis of the dGTP derivative is generally applicable to the synthesis of P3-(omega-aminoalk-1-yl)nucleoside triphosphate esters for the preparation of analogous affinity adsorbents. Ribonucleotide reductase can be rapidly purified to homogeneity, on a large scale, by use of dGTP-Sepharose and conditions for optimum recovery of the enzyme have been determined. The affinity of ribonucleotide reductase and other proteins for dGTP-Sepharose is increased by either raising the ionic strength or lowering the temperature of the eluent. Elution of the enzyme from the adsorbent can be achieved between pH 5.8 and 7.3, whereas at pH 5.3 the reductase is bound extremely tightly and cannot be recovered. Ribonucleotide reductase can be eluted from the adsorbent with dGTP or urea. Elution with urea is carried out at pH 6.3, where the enzyme is stable and maximum recovery is obtained. Affinity chromatography consistently produces ribonucleotide reductase of high specific activity (170-180 units/mg). In the presence of 0.1 to 1.2 M urea or hydroxyurea, the enzyme is inhibited, but allosteric activation is unchanged. No alteration in the structure or function of the reductase was detected when the enzyme was exposed to 2.0 M urea during elution from the affinity adsorbent, but exposure for longer periods causes some inactivation."}
{"id": "PMID:241390", "title": "Interpretation of the doublet at 850 and 830 cm-1 in the Raman spectra of tyrosyl residues in proteins and certain model compounds.", "content": "The doublet at 850 and 830 cm-1 in the Raman spectra of proteins containing tyrosyl residues has been examined as to its origin and the relation of its components to the environment of the phenyl ring, the state of the phenolic hydroxyl group, and the conformation of the amino acid backbone. Raman spectral studies on numerous model molecules related to tyrosine, including certain deuterium derivatives, show that the doublet is due to Fermi resonance between the ring-breathing vibration and the overtone of an out-of-plane ring-bending vibration of the para-substituted benzenes. Further examination of the effects of pH and solvents on the Fermi doublet and of the crystallographic data demonstrates that the intensity ratio of the two components depends on changes in the relative frequencies of the two vibrations. These in turn are found to be sensitive to the nature of the hydrogen bonding of the phenolic hydroxyl group of its ionization, but much less so to the environment of the phenyl ring and the conformation of the amino acid backbone. By use of the relative intensities of the doublet in model systems where the phenolic hydroxyl group is strongly hydrogen-bonded, weakly hydrogen-bonded, free or ionized, the reported Raman intensities of the doublets observed in the Raman spectra of several proteins have been interpreted. The results are compared with those obtained by other techniques.", "contents": "Interpretation of the doublet at 850 and 830 cm-1 in the Raman spectra of tyrosyl residues in proteins and certain model compounds. The doublet at 850 and 830 cm-1 in the Raman spectra of proteins containing tyrosyl residues has been examined as to its origin and the relation of its components to the environment of the phenyl ring, the state of the phenolic hydroxyl group, and the conformation of the amino acid backbone. Raman spectral studies on numerous model molecules related to tyrosine, including certain deuterium derivatives, show that the doublet is due to Fermi resonance between the ring-breathing vibration and the overtone of an out-of-plane ring-bending vibration of the para-substituted benzenes. Further examination of the effects of pH and solvents on the Fermi doublet and of the crystallographic data demonstrates that the intensity ratio of the two components depends on changes in the relative frequencies of the two vibrations. These in turn are found to be sensitive to the nature of the hydrogen bonding of the phenolic hydroxyl group of its ionization, but much less so to the environment of the phenyl ring and the conformation of the amino acid backbone. By use of the relative intensities of the doublet in model systems where the phenolic hydroxyl group is strongly hydrogen-bonded, weakly hydrogen-bonded, free or ionized, the reported Raman intensities of the doublets observed in the Raman spectra of several proteins have been interpreted. The results are compared with those obtained by other techniques."}
{"id": "PMID:241391", "title": "The mechanism of formylation of five-membered cyclic phosphorodiamidates.", "content": "Cyclic N,N'-diphenylethylenephosphorodiamidates, 1, have been found to yield up to 70% of the N-formyldiphenylethylenediamines when reacted in 1 M formate buffers (50 degrees, 25% v/v dioxane-H2O, mu = 1.0). The mechanism proposed for formylation on the basis of kinetic, product ratio, and 18O-labeling studies apparently involves cyclization of a formyl phosphoramidate-amine adduct derived from formate attack on 1H+, the process probably being catalyzed by intramolecular proton transfer between the phosphoryl moiety and aniline nitrogen. An oxygen is transferred from formate to inorganic phosphate in the net reaction. The initial site of formylation with dissymmetric 1 (p-CH3O, p-Cl) was shown by 18O incorporation studies to be the p-anisidine nitrogen, which also corresponds to the isomer of thermodynamic control. Attack by formate on 1H+, therefore, results in expulsion of the more basic nitrogen. Certain mechanistic aspects of the reaction might occur in the enzyme-catalyzed ATP-dependent formylation of tetrahydrofolic acid.", "contents": "The mechanism of formylation of five-membered cyclic phosphorodiamidates. Cyclic N,N'-diphenylethylenephosphorodiamidates, 1, have been found to yield up to 70% of the N-formyldiphenylethylenediamines when reacted in 1 M formate buffers (50 degrees, 25% v/v dioxane-H2O, mu = 1.0). The mechanism proposed for formylation on the basis of kinetic, product ratio, and 18O-labeling studies apparently involves cyclization of a formyl phosphoramidate-amine adduct derived from formate attack on 1H+, the process probably being catalyzed by intramolecular proton transfer between the phosphoryl moiety and aniline nitrogen. An oxygen is transferred from formate to inorganic phosphate in the net reaction. The initial site of formylation with dissymmetric 1 (p-CH3O, p-Cl) was shown by 18O incorporation studies to be the p-anisidine nitrogen, which also corresponds to the isomer of thermodynamic control. Attack by formate on 1H+, therefore, results in expulsion of the more basic nitrogen. Certain mechanistic aspects of the reaction might occur in the enzyme-catalyzed ATP-dependent formylation of tetrahydrofolic acid."}
{"id": "PMID:241393", "title": "Consideration of the Possibility that the slow step in protein denaturation reactions is due to cis-trans isomerism of proline residues.", "content": "A model is proposed to account for the observation that the denaturation of small proteins apparently occurs in two kinetic phases. It is suggested that only one of these phases--the fast one--is actually an unfolding process. The slow phase is assumed to arise from the cis-trans isomerism of proline residues in the denaturated protein. From model compound data, it is shown that the expected rate for isomerism is in satisfactory agreement with the rates actually observed for protein folding. It is also shown that a simple model of protein unfolding based on the isomerism concept is very successful in accounting for many known experimental characteristics of the kinetics and thermodynamic of protein denaturation. Thus, the model is able to predict that two kinetic phases will be seen in the transition region while none are seen in the base-line regions, that both the fast and slow refolding phases lead to the native protein as the product, that the fast phase becomes the only observable phase for jumps ending far in the denatured base-line region, that most or all small proteins show a limiting low-temperature activation energy of ca. 20,000 cal, and that the relaxtion time for the slow phase seen in cytochrome c denaturation is much shorter than for all other small proteins. By utilizing \"double-jump\" experiments, it is shown directly that the slow phase is not part of the unfolding process but that it corresponds to a transition among two or more denatured forms which have identical spectroscopic (286.5 nm) properties. Thus, the slow relaxation is \"invisible\" except in the transition region where it couples to the fast unfolding equilibrium. Finally, since the present model assumes that only one of the major kinetic phases seen in denaturation reactions is concerned with the denaturation process per se, it is in agreement with numerous thermodynamic studies which show consistency with the two-state model for unfolding.", "contents": "Consideration of the Possibility that the slow step in protein denaturation reactions is due to cis-trans isomerism of proline residues. A model is proposed to account for the observation that the denaturation of small proteins apparently occurs in two kinetic phases. It is suggested that only one of these phases--the fast one--is actually an unfolding process. The slow phase is assumed to arise from the cis-trans isomerism of proline residues in the denaturated protein. From model compound data, it is shown that the expected rate for isomerism is in satisfactory agreement with the rates actually observed for protein folding. It is also shown that a simple model of protein unfolding based on the isomerism concept is very successful in accounting for many known experimental characteristics of the kinetics and thermodynamic of protein denaturation. Thus, the model is able to predict that two kinetic phases will be seen in the transition region while none are seen in the base-line regions, that both the fast and slow refolding phases lead to the native protein as the product, that the fast phase becomes the only observable phase for jumps ending far in the denatured base-line region, that most or all small proteins show a limiting low-temperature activation energy of ca. 20,000 cal, and that the relaxtion time for the slow phase seen in cytochrome c denaturation is much shorter than for all other small proteins. By utilizing \"double-jump\" experiments, it is shown directly that the slow phase is not part of the unfolding process but that it corresponds to a transition among two or more denatured forms which have identical spectroscopic (286.5 nm) properties. Thus, the slow relaxation is \"invisible\" except in the transition region where it couples to the fast unfolding equilibrium. Finally, since the present model assumes that only one of the major kinetic phases seen in denaturation reactions is concerned with the denaturation process per se, it is in agreement with numerous thermodynamic studies which show consistency with the two-state model for unfolding."}
{"id": "PMID:241394", "title": "Acetylation of human serum albumin by p-nitrophenyl acetate.", "content": "Human serum albumin reacts very rapidly with p-nitrophenyl acetate (NphOAc). Rapid acetylation of the protein accompanies and largely accounts for the easily observed rapid formation of of p-nitrophenolate ion. One group is acetylated much faster than all others. It appears to be located in a high affinity binding site for small fatty acid anions, to have a pKa of 8.7, and a limiting bimolecular rate of reaction with NphOAc of approximately 3 X 10(4) M-1 sec-1 at alkaline pH values. Rapid reversible binding appears to be a major contributor to the high reaction velocity.", "contents": "Acetylation of human serum albumin by p-nitrophenyl acetate. Human serum albumin reacts very rapidly with p-nitrophenyl acetate (NphOAc). Rapid acetylation of the protein accompanies and largely accounts for the easily observed rapid formation of of p-nitrophenolate ion. One group is acetylated much faster than all others. It appears to be located in a high affinity binding site for small fatty acid anions, to have a pKa of 8.7, and a limiting bimolecular rate of reaction with NphOAc of approximately 3 X 10(4) M-1 sec-1 at alkaline pH values. Rapid reversible binding appears to be a major contributor to the high reaction velocity."}
{"id": "PMID:241395", "title": "Purification and properties of a ribosomal protein methylase from Eschericha coli Q13.", "content": "Ribosomal protein methylase has been purified from Escherichia coli strain Q13 using methyl-deficient 50S subunits as substrates. The purified enzyme (or enzyme complex) which is devoid of rRNA methylating activity is quite stable and has a pH optimum around 8.0. The Km for S-adenosyl-L-methionine is 3.2 muM. The molecular weight of the enzyme is 3.1 X 10(4); minor methylating activity was also detected for protein peaks with molecular weights of 1.7 X 10(4) and 5.6 X 10(4). Protein L11 is the major protein methylated by the purified enzyme. Product analysis revealed the presence of N epislon-trimethyllysine, a methylated neutral amino acid(s) previously observed in protein L11 and N epislon-monomethyllysine. Free ribosomal proteins were much better substrates for the methylation, indicating that methylation of 50S ribosomal proteins can occur before the complete assembly of the 50S ribosomal subunit.", "contents": "Purification and properties of a ribosomal protein methylase from Eschericha coli Q13. Ribosomal protein methylase has been purified from Escherichia coli strain Q13 using methyl-deficient 50S subunits as substrates. The purified enzyme (or enzyme complex) which is devoid of rRNA methylating activity is quite stable and has a pH optimum around 8.0. The Km for S-adenosyl-L-methionine is 3.2 muM. The molecular weight of the enzyme is 3.1 X 10(4); minor methylating activity was also detected for protein peaks with molecular weights of 1.7 X 10(4) and 5.6 X 10(4). Protein L11 is the major protein methylated by the purified enzyme. Product analysis revealed the presence of N epislon-trimethyllysine, a methylated neutral amino acid(s) previously observed in protein L11 and N epislon-monomethyllysine. Free ribosomal proteins were much better substrates for the methylation, indicating that methylation of 50S ribosomal proteins can occur before the complete assembly of the 50S ribosomal subunit."}
{"id": "PMID:241396", "title": "Coenzyme binding by native and chemically modified pig heart triphosphopyridine nucleotide dependent isocitrate dehydrogenase.", "content": "The binding of TPNH to native and chemically modified pig heart TPN-dependent isocitrate dehydrogenase was studied by the techniques of ultrafiltration and fluorescence enhancement. A single site (per peptide chain) was found for TPNH with a dissociation constant (KD = 1.45 muM) that is quantitatively comparable to the Michaelis constant. The oxidized coenzyme, TPN+, weakens the binding of TPNH. The substrate manganous isocitrate also inhibits the binding of TPNH and, reciprocally, TPNH inhibits the binding of manganous isocitrate, suggesting that binding to the reduced coenzyme and substrate sites is mutually exclusive. Ultrafiltration experiments with carbonyl [14C]TPN+ revealed the existence of two sites with a dissociation constant (49 muM) more than ten times higher than the Michaelis constant. This observation excludes a random mechanism for isocitrate dehydrogenase or a sequential mechanism in which TPN+ binds first. Four chemically modified isocitrate dehydrogenases have been prepared: enzyme inactivated by reaction of a single methionyl residue with iodoacetate, by modification of a glutamyl residue by glycinamide (in the presence of a water soluble carbodiimide), by reaction of four cysteines successively with 5,5'-dithiobis(2-nitrobenzoic acid) and potassium cyanide, or by addition of two cysteine residues to N-ethylmaleimide. These enzymes were tested for their ability to bind TPN+, TPNH, and manganous isocitrate. In the cases of the cysteinyl and glutamyl-modified enzymes, inactivation appears to be due primarily to loss of the ability to bind the substrate manganous isocitrate. In constrast, the methionyl residue may participate in the coenzyme binding site or, more likely, may be involved in a step in catalysis subsequent to binding.", "contents": "Coenzyme binding by native and chemically modified pig heart triphosphopyridine nucleotide dependent isocitrate dehydrogenase. The binding of TPNH to native and chemically modified pig heart TPN-dependent isocitrate dehydrogenase was studied by the techniques of ultrafiltration and fluorescence enhancement. A single site (per peptide chain) was found for TPNH with a dissociation constant (KD = 1.45 muM) that is quantitatively comparable to the Michaelis constant. The oxidized coenzyme, TPN+, weakens the binding of TPNH. The substrate manganous isocitrate also inhibits the binding of TPNH and, reciprocally, TPNH inhibits the binding of manganous isocitrate, suggesting that binding to the reduced coenzyme and substrate sites is mutually exclusive. Ultrafiltration experiments with carbonyl [14C]TPN+ revealed the existence of two sites with a dissociation constant (49 muM) more than ten times higher than the Michaelis constant. This observation excludes a random mechanism for isocitrate dehydrogenase or a sequential mechanism in which TPN+ binds first. Four chemically modified isocitrate dehydrogenases have been prepared: enzyme inactivated by reaction of a single methionyl residue with iodoacetate, by modification of a glutamyl residue by glycinamide (in the presence of a water soluble carbodiimide), by reaction of four cysteines successively with 5,5'-dithiobis(2-nitrobenzoic acid) and potassium cyanide, or by addition of two cysteine residues to N-ethylmaleimide. These enzymes were tested for their ability to bind TPN+, TPNH, and manganous isocitrate. In the cases of the cysteinyl and glutamyl-modified enzymes, inactivation appears to be due primarily to loss of the ability to bind the substrate manganous isocitrate. In constrast, the methionyl residue may participate in the coenzyme binding site or, more likely, may be involved in a step in catalysis subsequent to binding."}
{"id": "PMID:241397", "title": "Isolation and functional characterization of hemoglobin Casper: beta106(G8) Leu replaced by Pro.", "content": "Hemoglobin Casper (beta106Leu replaced by Pro) can be separated from hemoglobin (Hb) A by isoelectric focusing on polyacrylamide gel. This abnormal hemoglobin was estimated to be 30% of teh total by both isoelectric focusing and heat lability kinetics. Its oxygen equilibrium curves indicate a high oxygen affinity, low degree of subunit interaction, and a decreased Bohr effect. Mixtures of Hb Casper and Hb A appear to bind oxygen as if no hybrid molecules exist.", "contents": "Isolation and functional characterization of hemoglobin Casper: beta106(G8) Leu replaced by Pro. Hemoglobin Casper (beta106Leu replaced by Pro) can be separated from hemoglobin (Hb) A by isoelectric focusing on polyacrylamide gel. This abnormal hemoglobin was estimated to be 30% of teh total by both isoelectric focusing and heat lability kinetics. Its oxygen equilibrium curves indicate a high oxygen affinity, low degree of subunit interaction, and a decreased Bohr effect. Mixtures of Hb Casper and Hb A appear to bind oxygen as if no hybrid molecules exist."}
{"id": "PMID:241398", "title": "Chemically induced lipid phase separation in model membranes containing charged lipids: a spin label study.", "content": "The lipid distribution in binary mixed membranes containing charged and uncharged lipids and the effect of Ca2+ and polylysine on the lipid organization was studied by the spin label technique. Dipalmitoyl phosphatidic acid was the charged, and spin labelled dipalmitoyl lecithin was the uncharged (zwitterionic) component. The ESR spectra were analyzed in terms of the spin exchange frequency, Wex. By measuring Wex as a function of the molar percentage of labelled lecithin a distinction between a random and a heterogeneous lipid distribution could be made. It is established that mixed lecithin-phosphatidic acid membranes exhibit lipid segregation (or a miscibility gap) in the fluid state. Comparative experiments with bilayer and monolayer membranes strongly suggest a lateral lipid segregation. At low lecithin concentration, aggregates containing between 25% and 40% lecithin are formed in the fluid phosphatidic acid membrane. This phase separation in membranes containing charged lipids is understandable on the basis of the Gouy-Chapman theory of electric double layers. In dipalmitoyl lecithin and in dimyristoyl phosphatidylethanolamine membranes the labelled lecithin is randomly distributed above the phase transition and has a coefficient of lateral diffusion of D = 2.8-10(-8) cm2/s at 59 degrees C. Addition of Ca2+ dramatically increases the extent of phase separation in lecithin-phosphatidic acid membranes. This chemically (and isothermally) induced phase separation is caused by the formation of crystalline patches of the Ca2+-bound phosphatidic acid. Lecithin is squeezed out from these patches of rigid lipid. The observed dependence of Wex on the Ca2+ concentration could be interpreted quantitatively on the basis of a two-cluster model. At low lecithin and Ca2+ concentration clusters containing about 30 mol % lecithin are formed. At high lecithin or Ca2+ concentrations a second type of precipitation containing 100% lecithin starts to form in addition. A one-to-one binding of divalent ions and phosphatidic acid at pH 9 was assumed. Such a one-to-one binding at pH 9 was established for the case of Mn2+ using ESR spectroscopy. Polylysine leads to the same strong increase in the lecithin segregation as Ca2+. The transition of the phosphatidic acid bound by the polypeptide is shifted from Tt = 47.5 degrees to Tt = 62 degrees C. This finding suggests the possibility of cooperative conformational changes in the lipid matrix and in the surface proteins in biological membranes.", "contents": "Chemically induced lipid phase separation in model membranes containing charged lipids: a spin label study. The lipid distribution in binary mixed membranes containing charged and uncharged lipids and the effect of Ca2+ and polylysine on the lipid organization was studied by the spin label technique. Dipalmitoyl phosphatidic acid was the charged, and spin labelled dipalmitoyl lecithin was the uncharged (zwitterionic) component. The ESR spectra were analyzed in terms of the spin exchange frequency, Wex. By measuring Wex as a function of the molar percentage of labelled lecithin a distinction between a random and a heterogeneous lipid distribution could be made. It is established that mixed lecithin-phosphatidic acid membranes exhibit lipid segregation (or a miscibility gap) in the fluid state. Comparative experiments with bilayer and monolayer membranes strongly suggest a lateral lipid segregation. At low lecithin concentration, aggregates containing between 25% and 40% lecithin are formed in the fluid phosphatidic acid membrane. This phase separation in membranes containing charged lipids is understandable on the basis of the Gouy-Chapman theory of electric double layers. In dipalmitoyl lecithin and in dimyristoyl phosphatidylethanolamine membranes the labelled lecithin is randomly distributed above the phase transition and has a coefficient of lateral diffusion of D = 2.8-10(-8) cm2/s at 59 degrees C. Addition of Ca2+ dramatically increases the extent of phase separation in lecithin-phosphatidic acid membranes. This chemically (and isothermally) induced phase separation is caused by the formation of crystalline patches of the Ca2+-bound phosphatidic acid. Lecithin is squeezed out from these patches of rigid lipid. The observed dependence of Wex on the Ca2+ concentration could be interpreted quantitatively on the basis of a two-cluster model. At low lecithin and Ca2+ concentration clusters containing about 30 mol % lecithin are formed. At high lecithin or Ca2+ concentrations a second type of precipitation containing 100% lecithin starts to form in addition. A one-to-one binding of divalent ions and phosphatidic acid at pH 9 was assumed. Such a one-to-one binding at pH 9 was established for the case of Mn2+ using ESR spectroscopy. Polylysine leads to the same strong increase in the lecithin segregation as Ca2+. The transition of the phosphatidic acid bound by the polypeptide is shifted from Tt = 47.5 degrees to Tt = 62 degrees C. This finding suggests the possibility of cooperative conformational changes in the lipid matrix and in the surface proteins in biological membranes."}
{"id": "PMID:241399", "title": "Superoxide radicals and hydrogen peroxide formation in mitochondria from normal and neoplastic tissues.", "content": "Mitochondria from beef heart, Morris hepatoma 3924A and Ehrlich ascites tumor (Lettr\u00e9 mutant) have been studied with respect to hydrogen peroxidase and superoxide radical formation and the presence of superoxide dismutase activity (EC 1.15.1.1, superoxide:superoxide oxidoreductase). The generation of superoxide radicals and hydrogen peroxide occurs at the level of the membrane, being present also in mitochondrial fragments. Hepatoma and ascites mitochondria have little or no superoxide dismutase activity. Superoxide radicals appear to be precursors of hydrogen peroxide formation, the reaction being catalyzed by superoxide dismutase.", "contents": "Superoxide radicals and hydrogen peroxide formation in mitochondria from normal and neoplastic tissues. Mitochondria from beef heart, Morris hepatoma 3924A and Ehrlich ascites tumor (Lettr\u00e9 mutant) have been studied with respect to hydrogen peroxidase and superoxide radical formation and the presence of superoxide dismutase activity (EC 1.15.1.1, superoxide:superoxide oxidoreductase). The generation of superoxide radicals and hydrogen peroxide occurs at the level of the membrane, being present also in mitochondrial fragments. Hepatoma and ascites mitochondria have little or no superoxide dismutase activity. Superoxide radicals appear to be precursors of hydrogen peroxide formation, the reaction being catalyzed by superoxide dismutase."}
{"id": "PMID:241400", "title": "Purification and properties of S-adenosyl-L-methionine: caffeic acid O-methyltransferase from leaves of spinach beet (Beta vulgaris L).", "content": "1. An enzyme catalysing the methylation of caffeic acid to ferulic acid, using S-adenosyl-L-methionine as methyl donor, has been extracted from leaves of spinach beet and purified 75-fold to obtain a stable preparation. 2. The enzyme showed optimum activity at pH 6.5, and did not require the addition of Mg2+ for maximum activity. 3. It was most active with caffeic acid, but showed some activity with catechol, protocatechuic acid and 3,4-dihydroxybenzaldehyde. The Km for caffeic acid was 68 muM. 4. 4. The Km for S-adenosyl-L-methionine was 12.5 muM. S-Adenosyl-L-homocystein (Ki = 4.4 muM) was a competitive inhibitor of S-adenosyl-L-methionine. 5. The synthesis of S-adenosyl-L-homocysteine from adenosine and L-homocysteine and its consequent effect on caffeic acid methylation were demonstrated with a partially-purified preparation from spinach-beet leaves, which possessed both S-adenosyl-L-homocysteine hydrolase (EC 3.3.1.1) and adenosine nucleosidase (EC 3.2.2.7) activities. This preparation was also able to catalyse the rapid breakdown of S-adenosyl-L-homocysteine to adenosine and adenine; the possible significance of this reaction in relieving the inhibition of caffeic acid methylation by S-adenosyl-L-homocystein is discussed.", "contents": "Purification and properties of S-adenosyl-L-methionine: caffeic acid O-methyltransferase from leaves of spinach beet (Beta vulgaris L). 1. An enzyme catalysing the methylation of caffeic acid to ferulic acid, using S-adenosyl-L-methionine as methyl donor, has been extracted from leaves of spinach beet and purified 75-fold to obtain a stable preparation. 2. The enzyme showed optimum activity at pH 6.5, and did not require the addition of Mg2+ for maximum activity. 3. It was most active with caffeic acid, but showed some activity with catechol, protocatechuic acid and 3,4-dihydroxybenzaldehyde. The Km for caffeic acid was 68 muM. 4. 4. The Km for S-adenosyl-L-methionine was 12.5 muM. S-Adenosyl-L-homocystein (Ki = 4.4 muM) was a competitive inhibitor of S-adenosyl-L-methionine. 5. The synthesis of S-adenosyl-L-homocysteine from adenosine and L-homocysteine and its consequent effect on caffeic acid methylation were demonstrated with a partially-purified preparation from spinach-beet leaves, which possessed both S-adenosyl-L-homocysteine hydrolase (EC 3.3.1.1) and adenosine nucleosidase (EC 3.2.2.7) activities. This preparation was also able to catalyse the rapid breakdown of S-adenosyl-L-homocysteine to adenosine and adenine; the possible significance of this reaction in relieving the inhibition of caffeic acid methylation by S-adenosyl-L-homocystein is discussed."}
{"id": "PMID:241401", "title": "Photooxidation of alpha-glucan phosphorylases from rabbit muscle and potato tubers.", "content": "Photooxidation of alpha-glucan phosphorylases from rabbit muscle and potato tubers in the presence of rose bengal leads to a rapid loss of enzymatic activity which follows first-order kinetics. The process is pH dependent, being more rapid at higher pH. The inactivation is closely related to the destruction of histidine residues in the enzyme. It is suggested that histidine residues are largely responsible for the loss of enzymatic activity in the photooxidation. The inactivation of potato phosphorylase is retarded by substrates, whereas that of the muscle enzyme is not. The rate of photoinactivation of muscle phosphorylase b is increased with AMP, and decreased with ATP, ADP, IMP and glucose-6-P. This finding is considered to be closely related to the allosteric transition of phosphorylase.", "contents": "Photooxidation of alpha-glucan phosphorylases from rabbit muscle and potato tubers. Photooxidation of alpha-glucan phosphorylases from rabbit muscle and potato tubers in the presence of rose bengal leads to a rapid loss of enzymatic activity which follows first-order kinetics. The process is pH dependent, being more rapid at higher pH. The inactivation is closely related to the destruction of histidine residues in the enzyme. It is suggested that histidine residues are largely responsible for the loss of enzymatic activity in the photooxidation. The inactivation of potato phosphorylase is retarded by substrates, whereas that of the muscle enzyme is not. The rate of photoinactivation of muscle phosphorylase b is increased with AMP, and decreased with ATP, ADP, IMP and glucose-6-P. This finding is considered to be closely related to the allosteric transition of phosphorylase."}
{"id": "PMID:241402", "title": "Reactivation and aging of diphenyl phosphoryl acetylcholinesterase.", "content": "Acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) is readily in hibited by 10(-5) M diphenylphosphorochloridate even though the inhibitor hydrolyzes in a few seconds. The fluoridate is a much weaker inhibitor. The inhibited enzyme, diphenyl phosphoryl enzyme spontaneously recovers only about 50% of its activity with a half time of about 17 min at pH 7.0 and 6 min at pH 8.0. The fact that only 50% of the original activity returns is due to aging. The rates of reactivation and aging can be very greatly increased by a few percent of an organic solvent. Depending on the solvent even 1% may increase the rates by a factor of 5 or 6. The highest increase in rate was 70-fold. Quaternary NH+4 also increases the rates. Organic solvents and NH+4 also accelerate the reactivation of the much more stable diethyl phosphoryl enzyme derivative.", "contents": "Reactivation and aging of diphenyl phosphoryl acetylcholinesterase. Acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) is readily in hibited by 10(-5) M diphenylphosphorochloridate even though the inhibitor hydrolyzes in a few seconds. The fluoridate is a much weaker inhibitor. The inhibited enzyme, diphenyl phosphoryl enzyme spontaneously recovers only about 50% of its activity with a half time of about 17 min at pH 7.0 and 6 min at pH 8.0. The fact that only 50% of the original activity returns is due to aging. The rates of reactivation and aging can be very greatly increased by a few percent of an organic solvent. Depending on the solvent even 1% may increase the rates by a factor of 5 or 6. The highest increase in rate was 70-fold. Quaternary NH+4 also increases the rates. Organic solvents and NH+4 also accelerate the reactivation of the much more stable diethyl phosphoryl enzyme derivative."}
{"id": "PMID:241403", "title": "Purification and characterization of a phosphoprotein phosphatase from bovine adrenal cortex.", "content": "A phosphoprotein phosphatase which is active against chemically phosphorylated protamine has been purified about 500-fold from bovine adrenal cortex. The enzyme has a pH optimum between 7.5 and 8.0, and has an apparent Km for phosphoprotamine of about 50 muM. The hydrolysis of phosphoprotamine is stimulated by salt, and by Mn2+. Hydrolysis of phosphoprotamine is inhibited by ATP, ADP, AMP, and Pi, but is not affected by AMP or cyclic GMP. The purified phosphoprotein phosphatase preparation also dephosphorylates p-nitrophenyl phosphate and phosphohistone, and catalyzes the inactivation of liver phosphorylase, the inactivation of muscle phosphorylase a (and its conversion to phosphorylase b), and the inactivation of muscle phosphorylase b kinase. Phosphatase activities against phosphoprotamine and muscle phosphorylase a copurify over the last three stages of purification. Phosphoprotamine inhibits phosphorylase phosphatase activity, and muscle phosphorylase a inhibits the dephosphorylation of phosphoprotamine. These results suggest that one enzyme possesses both phosphoprotamine phosphatase and phosphorylase phosphatase activities. The stimulation of phosphorylase phosphatase activity, but not of phosphoprotamine phosphatase activity, by caffeine and by glucose, suggests that the different activities of this phosphoprotein phosphatase may be regulated separately.", "contents": "Purification and characterization of a phosphoprotein phosphatase from bovine adrenal cortex. A phosphoprotein phosphatase which is active against chemically phosphorylated protamine has been purified about 500-fold from bovine adrenal cortex. The enzyme has a pH optimum between 7.5 and 8.0, and has an apparent Km for phosphoprotamine of about 50 muM. The hydrolysis of phosphoprotamine is stimulated by salt, and by Mn2+. Hydrolysis of phosphoprotamine is inhibited by ATP, ADP, AMP, and Pi, but is not affected by AMP or cyclic GMP. The purified phosphoprotein phosphatase preparation also dephosphorylates p-nitrophenyl phosphate and phosphohistone, and catalyzes the inactivation of liver phosphorylase, the inactivation of muscle phosphorylase a (and its conversion to phosphorylase b), and the inactivation of muscle phosphorylase b kinase. Phosphatase activities against phosphoprotamine and muscle phosphorylase a copurify over the last three stages of purification. Phosphoprotamine inhibits phosphorylase phosphatase activity, and muscle phosphorylase a inhibits the dephosphorylation of phosphoprotamine. These results suggest that one enzyme possesses both phosphoprotamine phosphatase and phosphorylase phosphatase activities. The stimulation of phosphorylase phosphatase activity, but not of phosphoprotamine phosphatase activity, by caffeine and by glucose, suggests that the different activities of this phosphoprotein phosphatase may be regulated separately."}
{"id": "PMID:241404", "title": "Studies on phospholipase C from Pseudomonas aureofaciens. I. Purification and some properties of phospholipase C.", "content": "Phospholipase C (phosphatidylcholine cholinephosphohydrolase, EC 3.1.4.3) from Pseudomonas aureofaciens was purified 3600-fold from the culture filtrate with a recovery of 1.6%. Purification was performed with the useof (NH4)2SO4 precipitation, Sephadex G-100 gel filtration and by ion-exchange chromatography on DEAE-Sephadex A-50 and CM-Sephadex C-50. The purified enzyme appeared to be homogeneous as revealed by polyacrylamide disc gel electrophoresis at pH 9.3. The molecular weight was estimated to be 35 000 by gel filtration on Sephadex G-75. Under our experimental conditions, phosphatidylethanolamine was more rapidly hydrolysed than phosphatidylcholine. Lyso forms of these two phosphatides were poor substrates. Phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, cardiolipin and sphingomyelin were not hydrolysed. The enzyme activity with phosphatidylcholine as substrate was slightly stimulated by Ca2+, Mg2+, and Mn2+. However, these cations inhibited the activity with phosphatidylethanolamine as substrate. An anionic detergent, sodium deoxycholate, slightly enhanced the activity when phosphatidylcholine and phosphatidylethanolamine were used as substrates. A cationic detergent, cetyltrimethylammonium bromide, inhibited enzyme activity. EDTA and o-henanthroline inhibited the activity of the enzyme to a marked degree.", "contents": "Studies on phospholipase C from Pseudomonas aureofaciens. I. Purification and some properties of phospholipase C. Phospholipase C (phosphatidylcholine cholinephosphohydrolase, EC 3.1.4.3) from Pseudomonas aureofaciens was purified 3600-fold from the culture filtrate with a recovery of 1.6%. Purification was performed with the useof (NH4)2SO4 precipitation, Sephadex G-100 gel filtration and by ion-exchange chromatography on DEAE-Sephadex A-50 and CM-Sephadex C-50. The purified enzyme appeared to be homogeneous as revealed by polyacrylamide disc gel electrophoresis at pH 9.3. The molecular weight was estimated to be 35 000 by gel filtration on Sephadex G-75. Under our experimental conditions, phosphatidylethanolamine was more rapidly hydrolysed than phosphatidylcholine. Lyso forms of these two phosphatides were poor substrates. Phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, cardiolipin and sphingomyelin were not hydrolysed. The enzyme activity with phosphatidylcholine as substrate was slightly stimulated by Ca2+, Mg2+, and Mn2+. However, these cations inhibited the activity with phosphatidylethanolamine as substrate. An anionic detergent, sodium deoxycholate, slightly enhanced the activity when phosphatidylcholine and phosphatidylethanolamine were used as substrates. A cationic detergent, cetyltrimethylammonium bromide, inhibited enzyme activity. EDTA and o-henanthroline inhibited the activity of the enzyme to a marked degree."}
{"id": "PMID:241405", "title": "Studies on brain cytosol neuraminadase. I. Isolation and partial characterization of two forms of the enzyme from pig brain.", "content": "1. Two forms of cytosol neuraminidase (EC 3.2.1.18) (neuraminidase A and neuraminidase B) were isolated and purified from pig brain homogenate, by proceeding through the following steps: centrifugation of brain homogenate at 105 000 X g (1h); ammonium sulphate fractionation (35-55% saturated fraction); column chromatography on Biogel A 5 m; column chromatography on hydroxy apatite/cellulose gel; affinity chromatography on Affinose-tyrosyl-p-nitrophenyloxamic acid. The separation of the two forms of neuraminidase was provided by chromatography on hydroxylapatite/cellulose gel. Neuraminidase A was purified about 500-fold; neuraminidase B about 400-fold. 2. The pH optima and the maximum activities in various buffers were different for neuraminidase A and B (for instance the pH optimum was in sodium acetate/acetic acid buffer, 4.7 for neuraminidase A and 4.9 for neuraminidase B). Ions affected in a different way the two enzymes: K+ activated neuraminidase A but not neuraminidase B; Na+ and Li+ inhibited neuraminidase A at a higher degree than neuraminidase B. Neuraminidase B seemed to be moderately activated by some bivalent cations (Ca2+; Mg2+; Zn2+); neuraminidase A did not. The Km values for sialyllactose were different: 2.2-10(-3) M for neuramindase A; 0.46-10(-3) M for neuraminidase B.", "contents": "Studies on brain cytosol neuraminadase. I. Isolation and partial characterization of two forms of the enzyme from pig brain. 1. Two forms of cytosol neuraminidase (EC 3.2.1.18) (neuraminidase A and neuraminidase B) were isolated and purified from pig brain homogenate, by proceeding through the following steps: centrifugation of brain homogenate at 105 000 X g (1h); ammonium sulphate fractionation (35-55% saturated fraction); column chromatography on Biogel A 5 m; column chromatography on hydroxy apatite/cellulose gel; affinity chromatography on Affinose-tyrosyl-p-nitrophenyloxamic acid. The separation of the two forms of neuraminidase was provided by chromatography on hydroxylapatite/cellulose gel. Neuraminidase A was purified about 500-fold; neuraminidase B about 400-fold. 2. The pH optima and the maximum activities in various buffers were different for neuraminidase A and B (for instance the pH optimum was in sodium acetate/acetic acid buffer, 4.7 for neuraminidase A and 4.9 for neuraminidase B). Ions affected in a different way the two enzymes: K+ activated neuraminidase A but not neuraminidase B; Na+ and Li+ inhibited neuraminidase A at a higher degree than neuraminidase B. Neuraminidase B seemed to be moderately activated by some bivalent cations (Ca2+; Mg2+; Zn2+); neuraminidase A did not. The Km values for sialyllactose were different: 2.2-10(-3) M for neuramindase A; 0.46-10(-3) M for neuraminidase B."}
{"id": "PMID:241406", "title": "SH-proteinase from bean Phaseolus vulgaris var. Perlicka.", "content": "An SH-proteinase (EC 3.4.22.-) has been isolated from beans of the species Phaseolus vulgaris var. Perlicka. The enzyme is homogeneous when subjected to disc electrophoresis, electrofocusing and sedimentation analysis. The molecular weight was determined as 26,000-28,000 by gel filtration, 30,850 +/- 1500 by sedimentation analysis and 26,930-27,410 by calculation from the amino acid composition (Lys20-21, His3, Arg9, Asp21-22, Thr13, Ser18, Pro12-13, Glu23-24, Gly30, Ala16, Cys/29, Val19, Met1, Ile10, Leu13, Tyr14, Phe6, Trp3). The N-terminal amino acid of the proteinase is isoleucine. The effect of concentration, time of hydrolysis, pH, temperature, cations, anions, urea and guanidine - HCl on the proteolytic activity of the SH-proteinase was studied.", "contents": "SH-proteinase from bean Phaseolus vulgaris var. Perlicka. An SH-proteinase (EC 3.4.22.-) has been isolated from beans of the species Phaseolus vulgaris var. Perlicka. The enzyme is homogeneous when subjected to disc electrophoresis, electrofocusing and sedimentation analysis. The molecular weight was determined as 26,000-28,000 by gel filtration, 30,850 +/- 1500 by sedimentation analysis and 26,930-27,410 by calculation from the amino acid composition (Lys20-21, His3, Arg9, Asp21-22, Thr13, Ser18, Pro12-13, Glu23-24, Gly30, Ala16, Cys/29, Val19, Met1, Ile10, Leu13, Tyr14, Phe6, Trp3). The N-terminal amino acid of the proteinase is isoleucine. The effect of concentration, time of hydrolysis, pH, temperature, cations, anions, urea and guanidine - HCl on the proteolytic activity of the SH-proteinase was studied."}
{"id": "PMID:241407", "title": "Regulatory responses of arginine deiminase in whole cells of Clostridium sporogenes.", "content": "Arginine deiminase (EC 3.5.3.6) has been shown to have regulatory properties. The activity was observed to be sigmoidal with respect to substrate concentrations. Addition of histidine to the system caused the abolition of sigmoidal responses. The regulatory properties of the enzyme as well as the desensitising action of histidine could also be demonstrated with whole cell suspensions. The pH of the system also seemed to influence modulations in the enzyme.", "contents": "Regulatory responses of arginine deiminase in whole cells of Clostridium sporogenes. Arginine deiminase (EC 3.5.3.6) has been shown to have regulatory properties. The activity was observed to be sigmoidal with respect to substrate concentrations. Addition of histidine to the system caused the abolition of sigmoidal responses. The regulatory properties of the enzyme as well as the desensitising action of histidine could also be demonstrated with whole cell suspensions. The pH of the system also seemed to influence modulations in the enzyme."}
{"id": "PMID:241408", "title": "Dissociation of Tetrahymena 30 S dynein into 14 S subunit by sonication.", "content": "The sonication of 30 S dynein obtained from Tetrahymena cilia induced dissociation into 14-S subunits, some of the enzyme still remaining as intact 30 S dynein and partially dissociated dynein (21 S) in a minor amount. It was demonstrated that the enzymatic properties of the 14 S subunit are quite similar to those of 30 S dynein except for the Ca2+:Mg2+ ratio. ATPase (EC 3.6.1.3) (ATP phosphohydrolase activity of the 14 S subunit was steadily enhanced by increasing concentrations of Mg2+. It was also activated by Ca2+ with an optimum at 6 mM but inhibited by a further increase in concentration. The Ca2+:Mg2+ ratio at 1 mM was about 0.62. 0.6 M KCl stimulated ATPase activity of the 14 S subunit two-fold. The Mg2+-ATPase had an optimum at pH 6.2 and revealed a high activity over pH 10. The Ca2+-ATPase showed two optima at pH 6.2 and 9.5. The Km for ATP was 10 muM. Only 10% of the 14 S subunit recombined with the outer fibers in the presence of Mg2+. The 14 S subunit was shown to have the same mobility as that of 30 S dynein on sodium dodecyl sulfate-polyacrylamide gel electrophoresis.", "contents": "Dissociation of Tetrahymena 30 S dynein into 14 S subunit by sonication. The sonication of 30 S dynein obtained from Tetrahymena cilia induced dissociation into 14-S subunits, some of the enzyme still remaining as intact 30 S dynein and partially dissociated dynein (21 S) in a minor amount. It was demonstrated that the enzymatic properties of the 14 S subunit are quite similar to those of 30 S dynein except for the Ca2+:Mg2+ ratio. ATPase (EC 3.6.1.3) (ATP phosphohydrolase activity of the 14 S subunit was steadily enhanced by increasing concentrations of Mg2+. It was also activated by Ca2+ with an optimum at 6 mM but inhibited by a further increase in concentration. The Ca2+:Mg2+ ratio at 1 mM was about 0.62. 0.6 M KCl stimulated ATPase activity of the 14 S subunit two-fold. The Mg2+-ATPase had an optimum at pH 6.2 and revealed a high activity over pH 10. The Ca2+-ATPase showed two optima at pH 6.2 and 9.5. The Km for ATP was 10 muM. Only 10% of the 14 S subunit recombined with the outer fibers in the presence of Mg2+. The 14 S subunit was shown to have the same mobility as that of 30 S dynein on sodium dodecyl sulfate-polyacrylamide gel electrophoresis."}
{"id": "PMID:241410", "title": "Conformational studies on parvalbumins by circular dichroism.", "content": "Structural variations of two parvalbumins, Whiting III and Pike III, in various denaturing conditions, have been studied by circular dichroism. CD signals are depressed from 4 urea. For Pike III, acidic pH, sodium dodecyl sulfate or complete removal of Ca2+ show little effect in the far ultraviolet region but rather strong effects in the near ultraviolet. For Whiting III similar results are obtained at acidic pH. Carboxymethylated Whiting III (0.15 Ca2+/mol) shows, on the contrary, decreased CD signals in the far and in the near ultraviolet spectra. Addition of Ca2+ fully restores the native CD spectra in both proteins. Ca2+ binding produces structural modifications which are found to vary according to parvalbumin and which seem in any case different from those described for troponin C.", "contents": "Conformational studies on parvalbumins by circular dichroism. Structural variations of two parvalbumins, Whiting III and Pike III, in various denaturing conditions, have been studied by circular dichroism. CD signals are depressed from 4 urea. For Pike III, acidic pH, sodium dodecyl sulfate or complete removal of Ca2+ show little effect in the far ultraviolet region but rather strong effects in the near ultraviolet. For Whiting III similar results are obtained at acidic pH. Carboxymethylated Whiting III (0.15 Ca2+/mol) shows, on the contrary, decreased CD signals in the far and in the near ultraviolet spectra. Addition of Ca2+ fully restores the native CD spectra in both proteins. Ca2+ binding produces structural modifications which are found to vary according to parvalbumin and which seem in any case different from those described for troponin C."}
{"id": "PMID:241411", "title": "EPR studies on the anaerobic reduction of fungal laccase. Evidence for participation of type 2 copper in the reduction mechanism.", "content": "1. In anaerobic reduction studies on fungal laccase B (p-diphenol:O2 oxidoreductase, EC 1.14.18.1) with the EPR and stopped-flow techniques it was found that the type 2 copper of the enzyme is rapidly undergoing a reduction-oxidation cycle which is followed by a slower reduction in a couple of seconds. An intermediate EPR signal of unknown origin is formed in the same time-range as the initial reduction of type 2 copper and disappears again when this copper ion is reoxidized. 2. The rate of the anaerobic reoxidation of type 2 copper is similar to the reduction rate of the two-electron acceptor, suggesting that they are interacting in the electron transfer of the enzyme. 3. The changes in the reaction rates of both type 2 and type 3 copper appear to be affected in a similar way by changes in pH. 4. The EPR signal of the type 2 Cu2+ suggests that this ion is liganded to one or more nitrogens.", "contents": "EPR studies on the anaerobic reduction of fungal laccase. Evidence for participation of type 2 copper in the reduction mechanism. 1. In anaerobic reduction studies on fungal laccase B (p-diphenol:O2 oxidoreductase, EC 1.14.18.1) with the EPR and stopped-flow techniques it was found that the type 2 copper of the enzyme is rapidly undergoing a reduction-oxidation cycle which is followed by a slower reduction in a couple of seconds. An intermediate EPR signal of unknown origin is formed in the same time-range as the initial reduction of type 2 copper and disappears again when this copper ion is reoxidized. 2. The rate of the anaerobic reoxidation of type 2 copper is similar to the reduction rate of the two-electron acceptor, suggesting that they are interacting in the electron transfer of the enzyme. 3. The changes in the reaction rates of both type 2 and type 3 copper appear to be affected in a similar way by changes in pH. 4. The EPR signal of the type 2 Cu2+ suggests that this ion is liganded to one or more nitrogens."}
{"id": "PMID:241412", "title": "Involvement of tyrosine residues in the protomer-protomer interaction of Proteus mirabilis flagella as studied by spectroscopic methods, chemical modification and aggregation experiments.", "content": "Using spectrophotometrical titration, chemical modification, and ultraviolet difference spectral methods, the existence of at least two distinct tyrosine groups in the isolated flagellin of Proteus mirabilis flagella has been established. Three of the five flagellin tyrosines are buried in the protein matrix, whereas the other two seem to lie on the protein surface accessible to perturbants. Also about two tyrosine residues, presumably the latter ones exposed to the environment, can be nitrated with tetranitromethane in the monomeric flagellin with a concomitant loss of the polymerization ability after about one tyrosine per mol flagellin has been nitrated. Nitrated flagellin, homogeneous with respect to molecular weight, degree of nitration and isoelectric point, could be isolated and characterized. On the other hand, it could be shown that in the polymeric flagellum the phenolic groups of all five tyrosine residues are inaccessible to perturbing and modifying reagents. It seems, therefore, that the integrity of the phenolic groups is necessary for the proper folding and aggregation of the flagellin subunits to form the stable helical flagella.", "contents": "Involvement of tyrosine residues in the protomer-protomer interaction of Proteus mirabilis flagella as studied by spectroscopic methods, chemical modification and aggregation experiments. Using spectrophotometrical titration, chemical modification, and ultraviolet difference spectral methods, the existence of at least two distinct tyrosine groups in the isolated flagellin of Proteus mirabilis flagella has been established. Three of the five flagellin tyrosines are buried in the protein matrix, whereas the other two seem to lie on the protein surface accessible to perturbants. Also about two tyrosine residues, presumably the latter ones exposed to the environment, can be nitrated with tetranitromethane in the monomeric flagellin with a concomitant loss of the polymerization ability after about one tyrosine per mol flagellin has been nitrated. Nitrated flagellin, homogeneous with respect to molecular weight, degree of nitration and isoelectric point, could be isolated and characterized. On the other hand, it could be shown that in the polymeric flagellum the phenolic groups of all five tyrosine residues are inaccessible to perturbing and modifying reagents. It seems, therefore, that the integrity of the phenolic groups is necessary for the proper folding and aggregation of the flagellin subunits to form the stable helical flagella."}
{"id": "PMID:241413", "title": "The tyrosyl residues in creatine kinase. Modification by iodine.", "content": "The effect of the iodination of tyrosyl residues in creatine kinase from rabbit muscle has been investigated at alkaline pH after reversible masking of the reactive thiol groups. The conversion of 4-5 tyrosyl residues to monoiodotyrosines as measured by spectrotitration and by radioactive iodine labelling resulted in almost total loss of enzymic activity. The modified enzyme was unable to bind its nucleotide substrates but no significant conformational change was revealed by optical rotatory dispersion or Stokes radius measurements. However, change in the reactivity of some non-essential thiol groups, presumably those located near the active thiol groups, was observed.", "contents": "The tyrosyl residues in creatine kinase. Modification by iodine. The effect of the iodination of tyrosyl residues in creatine kinase from rabbit muscle has been investigated at alkaline pH after reversible masking of the reactive thiol groups. The conversion of 4-5 tyrosyl residues to monoiodotyrosines as measured by spectrotitration and by radioactive iodine labelling resulted in almost total loss of enzymic activity. The modified enzyme was unable to bind its nucleotide substrates but no significant conformational change was revealed by optical rotatory dispersion or Stokes radius measurements. However, change in the reactivity of some non-essential thiol groups, presumably those located near the active thiol groups, was observed."}
{"id": "PMID:241414", "title": "Enzymic and immunochemical properties of lysozyme. X. Conformation, enzymic activity and immunochemistry of lysozyme reduced at two carboxyl groups.", "content": "Reduction of lysozyme by diborane, followed by air oxidation of the reduced disulfides and chromatography on CM-cellulose, yielded a homogeneous derivative. In the derivative, the carboxyl groups of aspartic acid 119 and the end-chain leucine residue were reduced to their corresponding alcohols. Correct re-forming of the disulfide bonds was demonstrated by peptide mapping of the tryptic hydrolysates of the derivative and lysozyme without breaking the disulfide bonds, followed by identification of the disulfide-containing peptides. Correct disulfide pairing in the two-disulfide peptide in the tryptic hydrolysate was established from its immunochemical behavior. Preparations of the two-disulfide fragment from lysozyme and derivative had equal inhibitory activities (26 or 32%) of the reaction of lysozyme with two homologous antisera. In ORD measurements, lysozyme and the derivative had equal rotatory powers at neutral pH. However, the bo value for the derivative decreased by about 10%. Below pH 6.4 and above pH 8.0, the derivative was less rotatory than native lysozyme. In CD measurements at neutral pH, the negative ellipticity bands at 220 and 208 nm showed little or no decrease in the derivative relative to the native protein. Although conformational differences between the derivative and its parent protein were almost undetectable by ORD and CD measurements, they were readily detected by chemical monitoring of the conformation. In the derivative, both accessibility to tryptic hydrolysis and reducibility of the disulfide bonds increased markedly. The enzymic activity of the derivative was decreased but retained the same pH optimum. With antisera to lysozyme or antisera to the derivative, lysozyme and its derivative possessed equal antigenic reactivities. The immunochemical findings further confirm the correct refolding of the disulfides. Also, they indicate that aspartic acid 119 and the C-terminal leucine residue are not part of an antigenic reactive region in lysozyme.", "contents": "Enzymic and immunochemical properties of lysozyme. X. Conformation, enzymic activity and immunochemistry of lysozyme reduced at two carboxyl groups. Reduction of lysozyme by diborane, followed by air oxidation of the reduced disulfides and chromatography on CM-cellulose, yielded a homogeneous derivative. In the derivative, the carboxyl groups of aspartic acid 119 and the end-chain leucine residue were reduced to their corresponding alcohols. Correct re-forming of the disulfide bonds was demonstrated by peptide mapping of the tryptic hydrolysates of the derivative and lysozyme without breaking the disulfide bonds, followed by identification of the disulfide-containing peptides. Correct disulfide pairing in the two-disulfide peptide in the tryptic hydrolysate was established from its immunochemical behavior. Preparations of the two-disulfide fragment from lysozyme and derivative had equal inhibitory activities (26 or 32%) of the reaction of lysozyme with two homologous antisera. In ORD measurements, lysozyme and the derivative had equal rotatory powers at neutral pH. However, the bo value for the derivative decreased by about 10%. Below pH 6.4 and above pH 8.0, the derivative was less rotatory than native lysozyme. In CD measurements at neutral pH, the negative ellipticity bands at 220 and 208 nm showed little or no decrease in the derivative relative to the native protein. Although conformational differences between the derivative and its parent protein were almost undetectable by ORD and CD measurements, they were readily detected by chemical monitoring of the conformation. In the derivative, both accessibility to tryptic hydrolysis and reducibility of the disulfide bonds increased markedly. The enzymic activity of the derivative was decreased but retained the same pH optimum. With antisera to lysozyme or antisera to the derivative, lysozyme and its derivative possessed equal antigenic reactivities. The immunochemical findings further confirm the correct refolding of the disulfides. Also, they indicate that aspartic acid 119 and the C-terminal leucine residue are not part of an antigenic reactive region in lysozyme."}
{"id": "PMID:241415", "title": "Variations of lipid-protein interactions in erythrocyte ghosts as a function of temperature and pH in physiological and non-physiological ranges. A study using a paramagnetic quenching of protein fluorescence by nitroxide lipid analogues.", "content": "1. Incorporation of stearic acid nitroxides into erythrocyte ghosts markedly depresses the fluorescence of membrane protein tryptophan residues. 5-Nitroxide stearate quenches fluorescence more efficiently than 16-nitroxide stearate. Both compounds exhibit dynamic (diffusion-limited) quenching above 0.28 mumol/mg protein and static quenching at lower nitroxide protein ratios. Static quenching can be attributed to high affinity binding of nitroxide stearates by membrane protein. The dynamic phase represents distribution of the stearate analogues into a fluid lipid system. 2. Protein fluorophores accessible to quenching by a cholesterol analogue, androstane nitroxide, are saturated at low nitroxide/protein ratios (less than 0.14 mumol/mg protein), without resolution of a static quenching phase. This suggests that sterols are segregated away from protein, probably in CLusters\". 3. Paramagnetic quenching by stearate nitroxides increases abruptly between 35 and 50 degrees C. This discontinuous enhancement of quenching by temperature is reversible up to 41 degrees C but irreversible at higher temperatures. The discontinuity is also diminished by lowering pH from 7.3 through 6.5 to 6.0. Quenching by androstane nitroxide increases linearly with temperature up to approx. 41 degrees C and then rises exponentially. We attribute the reversible quenching thermotropism detected by stearate derivatives to reversible, thermotropic unfolding and/or depolymerisation of membrane proteins. The irreversible phase, detected also by the sterol derivative can be attributed to non-reversible protein denaturation. 4. Paramagnetic quenching of membrane tryptophan fluorescence by stearate derivatives is minimal at approx. pH 7.1 (35 degrees C) and increases sharply at lower and higher pH values, suggesting that two categories of protein residues, titrating between pH 6 and 8, profoundly influence the association of fatty acyl chains and penetrating protein segments. Quenching by androstane nitroxide exhibits no significant variation between pH 6 and 8, consistent with other data indicating that erythrocyte membrane sterols are segregated from membrane proteins, probably in clusters. 5. Our new approach confirms previous suggestions of a boundary layer of lipid in close association with some proteins in erythrocyte membranes, as well as experiments indicating that the lipid status in this boundary layer depends on that state of membrane proteins. However, sterols appear to be largely excluded from this boundary domain. Our data further show that lipid-protein interactions in erythrocyte membranes can vary significantly with fluctuations of temperature and pH in the physiological range.", "contents": "Variations of lipid-protein interactions in erythrocyte ghosts as a function of temperature and pH in physiological and non-physiological ranges. A study using a paramagnetic quenching of protein fluorescence by nitroxide lipid analogues. 1. Incorporation of stearic acid nitroxides into erythrocyte ghosts markedly depresses the fluorescence of membrane protein tryptophan residues. 5-Nitroxide stearate quenches fluorescence more efficiently than 16-nitroxide stearate. Both compounds exhibit dynamic (diffusion-limited) quenching above 0.28 mumol/mg protein and static quenching at lower nitroxide protein ratios. Static quenching can be attributed to high affinity binding of nitroxide stearates by membrane protein. The dynamic phase represents distribution of the stearate analogues into a fluid lipid system. 2. Protein fluorophores accessible to quenching by a cholesterol analogue, androstane nitroxide, are saturated at low nitroxide/protein ratios (less than 0.14 mumol/mg protein), without resolution of a static quenching phase. This suggests that sterols are segregated away from protein, probably in CLusters\". 3. Paramagnetic quenching by stearate nitroxides increases abruptly between 35 and 50 degrees C. This discontinuous enhancement of quenching by temperature is reversible up to 41 degrees C but irreversible at higher temperatures. The discontinuity is also diminished by lowering pH from 7.3 through 6.5 to 6.0. Quenching by androstane nitroxide increases linearly with temperature up to approx. 41 degrees C and then rises exponentially. We attribute the reversible quenching thermotropism detected by stearate derivatives to reversible, thermotropic unfolding and/or depolymerisation of membrane proteins. The irreversible phase, detected also by the sterol derivative can be attributed to non-reversible protein denaturation. 4. Paramagnetic quenching of membrane tryptophan fluorescence by stearate derivatives is minimal at approx. pH 7.1 (35 degrees C) and increases sharply at lower and higher pH values, suggesting that two categories of protein residues, titrating between pH 6 and 8, profoundly influence the association of fatty acyl chains and penetrating protein segments. Quenching by androstane nitroxide exhibits no significant variation between pH 6 and 8, consistent with other data indicating that erythrocyte membrane sterols are segregated from membrane proteins, probably in clusters. 5. Our new approach confirms previous suggestions of a boundary layer of lipid in close association with some proteins in erythrocyte membranes, as well as experiments indicating that the lipid status in this boundary layer depends on that state of membrane proteins. However, sterols appear to be largely excluded from this boundary domain. Our data further show that lipid-protein interactions in erythrocyte membranes can vary significantly with fluctuations of temperature and pH in the physiological range."}
{"id": "PMID:241416", "title": "Effect of ions on phospholipid layer structure as indicated by Raman spectroscopy.", "content": "Various anions and cations are found to induce changes in the layered structure of phosphatidylcholine-water systems as indicated by Raman Spectroscopy. From the ratio of Raman intensities, I1064/I1089, it is inferred that dipositive ions decrease the proportion of gauche character in the hydrocarbon chains, with the relative influence being: Ba2+ less than Mg2+ less than Ca2+ similar to Cd2+. Unipositive ions (Li+, K+ and Na+) produce no observed changes in the Raman spectrum of the lecithin dispersion. The proportion of gauche character of the hydrocarbon chains is found to be nearly independent of the anion for: Br-, Cl-, acetate-, I-, ClO4-, CNS- and SO42-. Dispersions prepared with a solution of KI+I2 produced Raman spectra in which the 1089cm-1 peak, which is characteristic of random lipid chains, was greatly intensified, presumably because of the presence of I3- which is known to penetrate the lipid lamellae. The observed trends are discussed.", "contents": "Effect of ions on phospholipid layer structure as indicated by Raman spectroscopy. Various anions and cations are found to induce changes in the layered structure of phosphatidylcholine-water systems as indicated by Raman Spectroscopy. From the ratio of Raman intensities, I1064/I1089, it is inferred that dipositive ions decrease the proportion of gauche character in the hydrocarbon chains, with the relative influence being: Ba2+ less than Mg2+ less than Ca2+ similar to Cd2+. Unipositive ions (Li+, K+ and Na+) produce no observed changes in the Raman spectrum of the lecithin dispersion. The proportion of gauche character of the hydrocarbon chains is found to be nearly independent of the anion for: Br-, Cl-, acetate-, I-, ClO4-, CNS- and SO42-. Dispersions prepared with a solution of KI+I2 produced Raman spectra in which the 1089cm-1 peak, which is characteristic of random lipid chains, was greatly intensified, presumably because of the presence of I3- which is known to penetrate the lipid lamellae. The observed trends are discussed."}
{"id": "PMID:241417", "title": "Sialic acid, electrophoretic mobility and transmembrane potentials of the Amphiuma red cell.", "content": "Red cells from the giant salamander Amphiuma means are shown to contain sialic acid. The amount removed by the action of neuraminidase is equal to that released by acid hydrolysis, indicating that all of the sialic acid is present on the outer surface of the plasma membrane. These cells have a negative electrophoretic mobility and 100% enzymatic removal of sialic acid results in a 40% reduction in the mobility, suggesting that either a fraction of the sialic acid carboxyl groups are unavailable to the action of external electric fields, or other negatively charged groups contribute to the surface charge. A further reduction in mobility of normal and sialic acid-free cells is caused by an increased extracellular calcium concentration. The negative groups affected by calcium are most likely to be phosphate groups, since the isoelectric point of the cells is found to lie between the pK values for H2PO-4 groups and the carboxyl groups of sialic acid. Membrane potentials of single cells, from which 80% or more of the total sialic acid had been removed, were identical to those measured in normal cells, confirming that sialic acid plays little, if any, direct role in the maintenance of membrane potentials and ionic permeabilities.", "contents": "Sialic acid, electrophoretic mobility and transmembrane potentials of the Amphiuma red cell. Red cells from the giant salamander Amphiuma means are shown to contain sialic acid. The amount removed by the action of neuraminidase is equal to that released by acid hydrolysis, indicating that all of the sialic acid is present on the outer surface of the plasma membrane. These cells have a negative electrophoretic mobility and 100% enzymatic removal of sialic acid results in a 40% reduction in the mobility, suggesting that either a fraction of the sialic acid carboxyl groups are unavailable to the action of external electric fields, or other negatively charged groups contribute to the surface charge. A further reduction in mobility of normal and sialic acid-free cells is caused by an increased extracellular calcium concentration. The negative groups affected by calcium are most likely to be phosphate groups, since the isoelectric point of the cells is found to lie between the pK values for H2PO-4 groups and the carboxyl groups of sialic acid. Membrane potentials of single cells, from which 80% or more of the total sialic acid had been removed, were identical to those measured in normal cells, confirming that sialic acid plays little, if any, direct role in the maintenance of membrane potentials and ionic permeabilities."}
{"id": "PMID:241419", "title": "High molecular weight deoxyribonucleic acid polymerase of LF hepatoma. Purification and properties.", "content": "A high molecular weight DNA polymerase has been purified from the cytosol of a fast growing hepatoma: LF hepatoma. This enzyme sediments at 11.3 S under polymerization reaction conditions (6 mM KCl) and at 8.3 S in higher salt concentrations (200 mM KCl). In either case, no activity is seen in the 3 to 4 S region where low molecular weight DNA polymerase is found. The purified enzyme has a neutral pH optimum and requires a divalent cation, all four deoxyribonucleoside triphosphates and an initiated DNA template for maximal activity. The synthetic template specificity of LF DNA polymerase has been studied. Although this enzyme cannot copy a polyribonucleotide template, the ribostrand of a synthetic hybrid can be used with low efficiency as an initiator for the synthesis of the complementary deoxyribonucleotide strand. The activity of the purified enzyme is strongly inhibited by thiol-blocking agents. The general properties of LF DNA polymerase are similar to those of high molecular weight mammalian DNA polymerases. In our experimental conditions, the error frequency of this tumoral DNA polymerase was no greater than that  made by the purified high molecular weight DNA polymerase of regenerating rat liver.", "contents": "High molecular weight deoxyribonucleic acid polymerase of LF hepatoma. Purification and properties. A high molecular weight DNA polymerase has been purified from the cytosol of a fast growing hepatoma: LF hepatoma. This enzyme sediments at 11.3 S under polymerization reaction conditions (6 mM KCl) and at 8.3 S in higher salt concentrations (200 mM KCl). In either case, no activity is seen in the 3 to 4 S region where low molecular weight DNA polymerase is found. The purified enzyme has a neutral pH optimum and requires a divalent cation, all four deoxyribonucleoside triphosphates and an initiated DNA template for maximal activity. The synthetic template specificity of LF DNA polymerase has been studied. Although this enzyme cannot copy a polyribonucleotide template, the ribostrand of a synthetic hybrid can be used with low efficiency as an initiator for the synthesis of the complementary deoxyribonucleotide strand. The activity of the purified enzyme is strongly inhibited by thiol-blocking agents. The general properties of LF DNA polymerase are similar to those of high molecular weight mammalian DNA polymerases. In our experimental conditions, the error frequency of this tumoral DNA polymerase was no greater than that  made by the purified high molecular weight DNA polymerase of regenerating rat liver."}
{"id": "PMID:241420", "title": "Alkaline lysis of mammalian cells for sedimentation analysis of nuclear DNA. Conformation of released DNA as monitored by physical, electron microscopic and enzymological techniques.", "content": "The degree of single strandedness of the DNA released from rat liver nuclei by various alkaline lysing solutions (including some with sodium dodecyl sulfate) was determined both before and after sedimentation in alkaline sucrose gradients employing electron microscopy, melting profiles, circular dichroism measurements, and digestibility by S1 nuclease. Regardless of the technique employed, the results obtained following alkaline sucrose gradient centrifugation of the DNA are consistent. The DNA was completely single stranded as judged by electron microscopy, circular dichroism spectra, and digestibility by S1 nuclease, an enzyme that specifically hydrolyzes single-stranded DNA. This was not true if the DNA was analyzed following alkaline lysis of the nuclei but before centrifugation. Under conditions which gave a complete transition to the single-stranded state, as judged by melting profiles and circular dichroism spectra, only 10-15% of the DNA was hydrolyzed by S1 nuclease. An increase in the susceptibility of the released DNA to S1 nuclease was observed with increases in the pH of the lysing solution. In order to release DNA which was single stranded as judged by both physical and enzymological techniques, the rat liver nuclei were lysed for 30 min with a 0.3 M NaOH lysing solution containing 0.5% dodecyl sulfate, 0.3 M NaCl and 0.03 M EDTA.", "contents": "Alkaline lysis of mammalian cells for sedimentation analysis of nuclear DNA. Conformation of released DNA as monitored by physical, electron microscopic and enzymological techniques. The degree of single strandedness of the DNA released from rat liver nuclei by various alkaline lysing solutions (including some with sodium dodecyl sulfate) was determined both before and after sedimentation in alkaline sucrose gradients employing electron microscopy, melting profiles, circular dichroism measurements, and digestibility by S1 nuclease. Regardless of the technique employed, the results obtained following alkaline sucrose gradient centrifugation of the DNA are consistent. The DNA was completely single stranded as judged by electron microscopy, circular dichroism spectra, and digestibility by S1 nuclease, an enzyme that specifically hydrolyzes single-stranded DNA. This was not true if the DNA was analyzed following alkaline lysis of the nuclei but before centrifugation. Under conditions which gave a complete transition to the single-stranded state, as judged by melting profiles and circular dichroism spectra, only 10-15% of the DNA was hydrolyzed by S1 nuclease. An increase in the susceptibility of the released DNA to S1 nuclease was observed with increases in the pH of the lysing solution. In order to release DNA which was single stranded as judged by both physical and enzymological techniques, the rat liver nuclei were lysed for 30 min with a 0.3 M NaOH lysing solution containing 0.5% dodecyl sulfate, 0.3 M NaCl and 0.03 M EDTA."}
{"id": "PMID:241421", "title": "[Analysis of ribosomes by polyacrylamide gel electrophoresis (author's transl)].", "content": "Ribosomal polymers, monomers and subunits from several eukaryotes and prokaryotes were isolated and analyzed by polyacrylamide gel electrophoresis. Extraction of RNA from ribosomal particles after their migration in a polyacrylamide gel, analyses by sedimentation in sucrose gradients and observations in the electron microscope were carried out in parallel. Attention was directed to the reproducibility, the precision and the limitations of the electrophoresis technique.", "contents": "[Analysis of ribosomes by polyacrylamide gel electrophoresis (author's transl)]. Ribosomal polymers, monomers and subunits from several eukaryotes and prokaryotes were isolated and analyzed by polyacrylamide gel electrophoresis. Extraction of RNA from ribosomal particles after their migration in a polyacrylamide gel, analyses by sedimentation in sucrose gradients and observations in the electron microscope were carried out in parallel. Attention was directed to the reproducibility, the precision and the limitations of the electrophoresis technique."}
{"id": "PMID:241422", "title": "Effect of plasma lipoproteins and lecithin-cholesterol dispersions on the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase of isolated rat hepatocytes.", "content": "Incubation of rat hepatocytes for 3 h in a medium containing amino acids, salts and albumin resulted in a 2-fold increase in the activity of 3-hydroxy-3-methylglutaryl-CoA reductase. Inclusion of 10% human plasma, rat serum or dialysed rat serum in the medium resulted in an approximate 7-fold increase in reductase activity. These increases were specific since there was little change in the rate of fatty acid synthesis or in the activity of tyrosine aminotransferase. Reductase levels were increased above control values when high density lipoproteins or leithin dispersions were added to the cells. Lecithin dispersions were also shown to increase the rate of efflux of cell cholesterol to the medium. In contrast, reductase levels were reduced when cells were incubated with low density lipoproteins or cholesterol added as an equimolar cholesterol-lecithin dispersion. This inhibition of the reductase by cholesterol dispersions was dependent on the continued de novo protein synthesis. Our data indicate that in normal rat hepatocytes the relative rates of efflux and influx of cholesterol may be critical to the regulation of 3-hydroxy-3-methylglutaryl-CoA reductase activity and cholesterogenesis.", "contents": "Effect of plasma lipoproteins and lecithin-cholesterol dispersions on the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase of isolated rat hepatocytes. Incubation of rat hepatocytes for 3 h in a medium containing amino acids, salts and albumin resulted in a 2-fold increase in the activity of 3-hydroxy-3-methylglutaryl-CoA reductase. Inclusion of 10% human plasma, rat serum or dialysed rat serum in the medium resulted in an approximate 7-fold increase in reductase activity. These increases were specific since there was little change in the rate of fatty acid synthesis or in the activity of tyrosine aminotransferase. Reductase levels were increased above control values when high density lipoproteins or leithin dispersions were added to the cells. Lecithin dispersions were also shown to increase the rate of efflux of cell cholesterol to the medium. In contrast, reductase levels were reduced when cells were incubated with low density lipoproteins or cholesterol added as an equimolar cholesterol-lecithin dispersion. This inhibition of the reductase by cholesterol dispersions was dependent on the continued de novo protein synthesis. Our data indicate that in normal rat hepatocytes the relative rates of efflux and influx of cholesterol may be critical to the regulation of 3-hydroxy-3-methylglutaryl-CoA reductase activity and cholesterogenesis."}
{"id": "PMID:241423", "title": "Phospholipase C from Clostridium novyi type A. I.", "content": "1. Phospholipase C (EC 3.1.4.3) from Clostridium novyi (oedematiens) type A was purified 2000-fold by (NH4)2SO4 precipitation, DEAE-Sephadex treatment in a batchwise system and Sephadex G-100 column chromatography. 2. The purified preparation had a specific activity of 95 mumol per min per mg protein toward phosphatidylcholine. This preparation was free from protease, lipase and oxygen-labile delta-hemolysin. 3. Phosphatidylcholine was hydrolyzed at the highest rate, while sphingomyelin and lysophosphatidylcholine were hydrolyzed at much lower rates. 4. Sodium deoxycholate and divalent cations such as Mg2+ and Ca2+ were extremely effective in stimulating phosphatidylcholine-hydrolyzing activity of this enzyme. 5. This enzyme hemolyzed horse red cells by hydrolyzing phosphatidylcholine, spingomyelin and phosphatidylethanolamine.", "contents": "Phospholipase C from Clostridium novyi type A. I. 1. Phospholipase C (EC 3.1.4.3) from Clostridium novyi (oedematiens) type A was purified 2000-fold by (NH4)2SO4 precipitation, DEAE-Sephadex treatment in a batchwise system and Sephadex G-100 column chromatography. 2. The purified preparation had a specific activity of 95 mumol per min per mg protein toward phosphatidylcholine. This preparation was free from protease, lipase and oxygen-labile delta-hemolysin. 3. Phosphatidylcholine was hydrolyzed at the highest rate, while sphingomyelin and lysophosphatidylcholine were hydrolyzed at much lower rates. 4. Sodium deoxycholate and divalent cations such as Mg2+ and Ca2+ were extremely effective in stimulating phosphatidylcholine-hydrolyzing activity of this enzyme. 5. This enzyme hemolyzed horse red cells by hydrolyzing phosphatidylcholine, spingomyelin and phosphatidylethanolamine."}
{"id": "PMID:241424", "title": "Factors effecting the solubilisation of stearoyl-coA desaturase of hen liver microsomes.", "content": "1. The lipid requirement for maximum desaturase activity was investigated using acetone/water mixtures. It was shown that for maximum stearoyl-CoA desaturase activity of hen liver microsomes neither the total neutral lipid fraction nor 44% of the phospholipid fraction were required. 2. The effect of sodium deoxycholate, Triton X-100, Nonidet P-40 and Bio-solv on the enzyme activity indicated that the neutral detergents had a milder effect than the ionic detergent but both classes could cause considerable irreversible loss of activity. 3. The treatment of the microsomes with 2.5% (v/v) water in acetone greatly improved the effective solubilising power of Triton X-100. The yield of desaturase in the 100 000 X g supernatant obtained by treating the microsomal fraction in this way was strongly dependent upon protein concentration. Maximum solubilisation was achieved with25 mg protein per ml 1% (w/v) Triton X-100 in 0.1 M potassium phosphate buffer pH 7.4. 4. A comparison of the properties of the solubilised and membrane-bound enzyme was made by an investigation of: (i) the temperature and pH optimum, (ii) activation energy and (iii) the effect of inhibitors on the enzyme activity.", "contents": "Factors effecting the solubilisation of stearoyl-coA desaturase of hen liver microsomes. 1. The lipid requirement for maximum desaturase activity was investigated using acetone/water mixtures. It was shown that for maximum stearoyl-CoA desaturase activity of hen liver microsomes neither the total neutral lipid fraction nor 44% of the phospholipid fraction were required. 2. The effect of sodium deoxycholate, Triton X-100, Nonidet P-40 and Bio-solv on the enzyme activity indicated that the neutral detergents had a milder effect than the ionic detergent but both classes could cause considerable irreversible loss of activity. 3. The treatment of the microsomes with 2.5% (v/v) water in acetone greatly improved the effective solubilising power of Triton X-100. The yield of desaturase in the 100 000 X g supernatant obtained by treating the microsomal fraction in this way was strongly dependent upon protein concentration. Maximum solubilisation was achieved with25 mg protein per ml 1% (w/v) Triton X-100 in 0.1 M potassium phosphate buffer pH 7.4. 4. A comparison of the properties of the solubilised and membrane-bound enzyme was made by an investigation of: (i) the temperature and pH optimum, (ii) activation energy and (iii) the effect of inhibitors on the enzyme activity."}
{"id": "PMID:241425", "title": "Isolation of peroxisomes from the dog kidney cortex.", "content": "The present study was undertaken to separate peroxisomes of the dog kidney cortex by the methods of discontinuous sucrose density gradient and zonal centrifugation. The separation of subcellular particles was evaluated by measuring the activities of reference enzymes, beta-glycerophosphatase for lysosomes, succinate dehydrogenase for mitochondria, glucose-6-phosphatase for microsomes, and catalase and D-amino acid oxidase for peroxisomes. The activities of D-amino acid oxidase and catalase were mainly observed in fractions 1 and 2 (1.6 and 1.7 M sucrose) obtained by discontinuous sucrose density-gradient centrifugation. Small amounts of acid phosphatase and succinate dehydrogenase contaminated these fractions. Considerably higher activity of catalase was determined in the supernatant, while D-amino acid oxidase showed a lower activity. By the method of zonal centrifugation, the highest specific activities of catalase and D-amino acid oxidase were found in fraction 50 (1.73 M sucrose) with no succinate dehydrogenase, acid phosphatase or glucose-6-phosphatase activity. These results suggested that peroxisomes of dog kidney cortex were clearly separated in 1.73 M sucrose from mitochondria, lysosomes and microsomes by zonal centrifugation.", "contents": "Isolation of peroxisomes from the dog kidney cortex. The present study was undertaken to separate peroxisomes of the dog kidney cortex by the methods of discontinuous sucrose density gradient and zonal centrifugation. The separation of subcellular particles was evaluated by measuring the activities of reference enzymes, beta-glycerophosphatase for lysosomes, succinate dehydrogenase for mitochondria, glucose-6-phosphatase for microsomes, and catalase and D-amino acid oxidase for peroxisomes. The activities of D-amino acid oxidase and catalase were mainly observed in fractions 1 and 2 (1.6 and 1.7 M sucrose) obtained by discontinuous sucrose density-gradient centrifugation. Small amounts of acid phosphatase and succinate dehydrogenase contaminated these fractions. Considerably higher activity of catalase was determined in the supernatant, while D-amino acid oxidase showed a lower activity. By the method of zonal centrifugation, the highest specific activities of catalase and D-amino acid oxidase were found in fraction 50 (1.73 M sucrose) with no succinate dehydrogenase, acid phosphatase or glucose-6-phosphatase activity. These results suggested that peroxisomes of dog kidney cortex were clearly separated in 1.73 M sucrose from mitochondria, lysosomes and microsomes by zonal centrifugation."}
{"id": "PMID:241426", "title": "Hydrolysis of nucleoside phosphates: IV. The metal ion-nucleic base interaction in the Cu2+-promoted dephosphorylation of the 5'-di- and 5'-triphosphates of cytidine, inosine and guanosine, and their protection toward hydrolysis by coordination to Cu(2,2'-bipyridyl)2+.", "content": "The dephosphorylation of CTP, GTP, ITP, ATP, CDP, GDP, IDP and ADP was characterized by measuring the first-order rate constant (50 degrees; I = 0.1, NaClO4) in dependence on pH (2 to 10). Except with CTP and CDP, the reactions are significantly accelerated by Cu2+ and pass through pH optima. By computing the pH dependence of the distribution of the several species present in the nucleotide (NP) systems, it is shown that the most reactive species is Cu(NP). Cu(NP-H), where N(1) is deprotonated, is somewhat less reactive. In both types of complexes, a metal ion-nucleic base interaction, which is responsible for the increased reactivity, occurs, i.e., macrochelates involving the phosphate chains and the base moieties are formed. In accord herewith, CTP and CDP are rather stable as the coordination tendency of the cytosine moiety is small. Furthermore, in the ternary complexes Cu(2,2'-bipyridyl)(NP) and Cu-(2,2'-bipyridyl)(NP-H), where the formation of a macrochelate is inhibited, the nucleotides are protected. The structure-reactivity relationship is also evident with Cu(ITP)2- and Cu(IDP)- which exist only in part as macrochelates; hence, they are less reactive than for example Cu(ATP)2- or Cu(ADP)-. With the aid of the initial rate, vo = d[PO4(3-)]/dt, the rate laws of the ascending side of the pH optima were determined: vo = k[Cu(NP)]/[H+]. A reaction mechanism that includes an intermolecular attack of OH- at the terminal phosphate group is proposed. The descending side of the pH optimum is attributed to the formation of CU(NP)(OH) or Cu(NP-H)(OH), where the Cu2+-base interaction is insignificant. However, these hydroxy complexes are still somewhat faster dephosphorylated than the free nucleotides. This is attributed to an intramolecular attack of the bound OH- at the terminal phosphate group.", "contents": "Hydrolysis of nucleoside phosphates: IV. The metal ion-nucleic base interaction in the Cu2+-promoted dephosphorylation of the 5'-di- and 5'-triphosphates of cytidine, inosine and guanosine, and their protection toward hydrolysis by coordination to Cu(2,2'-bipyridyl)2+. The dephosphorylation of CTP, GTP, ITP, ATP, CDP, GDP, IDP and ADP was characterized by measuring the first-order rate constant (50 degrees; I = 0.1, NaClO4) in dependence on pH (2 to 10). Except with CTP and CDP, the reactions are significantly accelerated by Cu2+ and pass through pH optima. By computing the pH dependence of the distribution of the several species present in the nucleotide (NP) systems, it is shown that the most reactive species is Cu(NP). Cu(NP-H), where N(1) is deprotonated, is somewhat less reactive. In both types of complexes, a metal ion-nucleic base interaction, which is responsible for the increased reactivity, occurs, i.e., macrochelates involving the phosphate chains and the base moieties are formed. In accord herewith, CTP and CDP are rather stable as the coordination tendency of the cytosine moiety is small. Furthermore, in the ternary complexes Cu(2,2'-bipyridyl)(NP) and Cu-(2,2'-bipyridyl)(NP-H), where the formation of a macrochelate is inhibited, the nucleotides are protected. The structure-reactivity relationship is also evident with Cu(ITP)2- and Cu(IDP)- which exist only in part as macrochelates; hence, they are less reactive than for example Cu(ATP)2- or Cu(ADP)-. With the aid of the initial rate, vo = d[PO4(3-)]/dt, the rate laws of the ascending side of the pH optima were determined: vo = k[Cu(NP)]/[H+]. A reaction mechanism that includes an intermolecular attack of OH- at the terminal phosphate group is proposed. The descending side of the pH optimum is attributed to the formation of CU(NP)(OH) or Cu(NP-H)(OH), where the Cu2+-base interaction is insignificant. However, these hydroxy complexes are still somewhat faster dephosphorylated than the free nucleotides. This is attributed to an intramolecular attack of the bound OH- at the terminal phosphate group."}
{"id": "PMID:241430", "title": "Occurrence and properties of fetal intestinal glycosidases (disaccharidases) in human amniotic fluid.", "content": "alpha-Glucosidase, beta-glucosidase and beta-galactosidase were studied in cell-free amniotic fluid samples using corresponding 4-methylumbelliferyl-glycosides and a series of disaccharides (maltose, sucrose, trehalose, turanose, cellobiose, gentiobiose and lactose) as substrates. The glycosidases exhibited several properties of intestinal disaccharidases such as pH optimum between 5.2 and 6.4, more activity towards the disaccharides than the artificial substrates, tight association of the activities with sedimentable complexes and beta-glucosidase and beta-galactosidase activities exerted by a single catalytic site. With the disaccharides as substrates, the amniotic fluid glycosidase activities were well correlated to those reported in the literature for fetal intestine of corresponding gestational ages. The presence of intestinal disaccharidases in amniotic fluid indicates that the fetal intestine contributes to the protein and enzymes of amniotic fluid.", "contents": "Occurrence and properties of fetal intestinal glycosidases (disaccharidases) in human amniotic fluid. alpha-Glucosidase, beta-glucosidase and beta-galactosidase were studied in cell-free amniotic fluid samples using corresponding 4-methylumbelliferyl-glycosides and a series of disaccharides (maltose, sucrose, trehalose, turanose, cellobiose, gentiobiose and lactose) as substrates. The glycosidases exhibited several properties of intestinal disaccharidases such as pH optimum between 5.2 and 6.4, more activity towards the disaccharides than the artificial substrates, tight association of the activities with sedimentable complexes and beta-glucosidase and beta-galactosidase activities exerted by a single catalytic site. With the disaccharides as substrates, the amniotic fluid glycosidase activities were well correlated to those reported in the literature for fetal intestine of corresponding gestational ages. The presence of intestinal disaccharidases in amniotic fluid indicates that the fetal intestine contributes to the protein and enzymes of amniotic fluid."}
{"id": "PMID:241431", "title": "Glutamine synthetase and glutamyltransferase in developing chick and rat tissues.", "content": "Concomitant determination of gamma-glutamine-hydroxylamine-glutamyltransferase (GT) and gamma-glutamyl hydroxamate synthetase (GS) activities in chick retina, brain and liver between the 13th day of incubation and a day after hatching showed that while both activities increased late in incubation, in neural tissues their rises were not simultaneous throughout development; in liver both activities were already high on the 14th day of incubation and changed in parallel thereafter. GS and GT activities could be evoked prematurely in all three tissues by cortisol, but GT activity showed higher responses to the hormone. GT and GS were separable by differential solubilization in chick liver but not in retina of chick or rat. The wide spread of the ratios of GT:GS activities in homogenates of a number of chick and rat tissues (1:1 to 73:1) indicates that the GS reaction is not catalyzed by the same protein that catalyzes the GT reactions. Relative amounts of GT(T) (free of GS activity) and of variants of GS (with different competences to catalyze the GT reaction) may govern the changes between the two activities during development and their distribution among different adult tissues in chick and rat.", "contents": "Glutamine synthetase and glutamyltransferase in developing chick and rat tissues. Concomitant determination of gamma-glutamine-hydroxylamine-glutamyltransferase (GT) and gamma-glutamyl hydroxamate synthetase (GS) activities in chick retina, brain and liver between the 13th day of incubation and a day after hatching showed that while both activities increased late in incubation, in neural tissues their rises were not simultaneous throughout development; in liver both activities were already high on the 14th day of incubation and changed in parallel thereafter. GS and GT activities could be evoked prematurely in all three tissues by cortisol, but GT activity showed higher responses to the hormone. GT and GS were separable by differential solubilization in chick liver but not in retina of chick or rat. The wide spread of the ratios of GT:GS activities in homogenates of a number of chick and rat tissues (1:1 to 73:1) indicates that the GS reaction is not catalyzed by the same protein that catalyzes the GT reactions. Relative amounts of GT(T) (free of GS activity) and of variants of GS (with different competences to catalyze the GT reaction) may govern the changes between the two activities during development and their distribution among different adult tissues in chick and rat."}
{"id": "PMID:241432", "title": "Non-ionic diffusion of pentobarbital across human chorion laeve.", "content": "Diffusion of the weak organic acid, pentobarbital, across human chorion laeve in vitro shows an inverse correlation with pH, when corrected for extracellular space permeation by the concurrent measurement of membrane permeability to the lipid insoluble molecule, p-aminohippurate. The temperature dependence of pentobarbital diffusion at different pHs supports the concept that the additional net flux of solute at lower pH occurs by transcellular permeation by the non-ionized moiety, the observed increase corresponding roughly to the dissociation curve for pentobarbital.", "contents": "Non-ionic diffusion of pentobarbital across human chorion laeve. Diffusion of the weak organic acid, pentobarbital, across human chorion laeve in vitro shows an inverse correlation with pH, when corrected for extracellular space permeation by the concurrent measurement of membrane permeability to the lipid insoluble molecule, p-aminohippurate. The temperature dependence of pentobarbital diffusion at different pHs supports the concept that the additional net flux of solute at lower pH occurs by transcellular permeation by the non-ionized moiety, the observed increase corresponding roughly to the dissociation curve for pentobarbital."}
{"id": "PMID:241433", "title": "Interaction of mescaline with phenothiazines: effect on behavior, body temperature, and tissue levels of hallucinogen in mice.", "content": "Mescaline (25 mg/kg; 66 muc/kg) was injected (ip) in mice 45 min before chlorpromazine (CPZ, 2.5, 5, 15 mg/kg), thioridazine (10, 30, 45 mg/kg), or chlorpromazine-sulfoxide (CPZ-SO, 15 mg/kg). Excitement, agitation, slight increase in ventilation and occasional head-shaking were seen 30 min after mescaline and continued for 30-45 min thereafter; locomotor activity and the number of scratching events were significantly increased during this period. CPZ (2.5, 5, 15 mg/kg) and thioridazine (10, 30, 45 mg/kg) partially or completely blocked mescaline-induced gross behavior; CPZ-SO (15 mg/kg) was not effective. Increased scratching responses and locomotor activity induced by mescaline were antagonized by all doses of CPZ and thioridazine; at higher doses, both CPZ (7.5, 15 mg/kg) and thioridazine (45 mg/kg) induced cataleptic-like condition and marked hypothermia. Tissue levels of mescaline, examined 3 hr after its administration, were increased by all doses of CPZ and a higher dose of thioridazine (45 mg/kg); CPZ-SO and lower doses of thioridazine had no effect.", "contents": "Interaction of mescaline with phenothiazines: effect on behavior, body temperature, and tissue levels of hallucinogen in mice. Mescaline (25 mg/kg; 66 muc/kg) was injected (ip) in mice 45 min before chlorpromazine (CPZ, 2.5, 5, 15 mg/kg), thioridazine (10, 30, 45 mg/kg), or chlorpromazine-sulfoxide (CPZ-SO, 15 mg/kg). Excitement, agitation, slight increase in ventilation and occasional head-shaking were seen 30 min after mescaline and continued for 30-45 min thereafter; locomotor activity and the number of scratching events were significantly increased during this period. CPZ (2.5, 5, 15 mg/kg) and thioridazine (10, 30, 45 mg/kg) partially or completely blocked mescaline-induced gross behavior; CPZ-SO (15 mg/kg) was not effective. Increased scratching responses and locomotor activity induced by mescaline were antagonized by all doses of CPZ and thioridazine; at higher doses, both CPZ (7.5, 15 mg/kg) and thioridazine (45 mg/kg) induced cataleptic-like condition and marked hypothermia. Tissue levels of mescaline, examined 3 hr after its administration, were increased by all doses of CPZ and a higher dose of thioridazine (45 mg/kg); CPZ-SO and lower doses of thioridazine had no effect."}
{"id": "PMID:241434", "title": "Monitoring in newborn intensive care.", "content": "The major difference between adult and newborn intensive care is the importance in the latter of respiratory problems requiring extensive surveillance and support. Impaired gas exchange in the lung, together with disturbed breathing patterns, often including the temporary cessation of breathing (apnoea), are characteristic of respiratory distress in pre-term infants. New apnoea monitors continue to be introduced, and the recent development of means for the continuous measurement of arterial oxygen in the newborn, thus allowing dangerously high and low oxygen levels to be avoided, must represent a significant advance in both physiological measurement and neonatal intensive care.", "contents": "Monitoring in newborn intensive care. The major difference between adult and newborn intensive care is the importance in the latter of respiratory problems requiring extensive surveillance and support. Impaired gas exchange in the lung, together with disturbed breathing patterns, often including the temporary cessation of breathing (apnoea), are characteristic of respiratory distress in pre-term infants. New apnoea monitors continue to be introduced, and the recent development of means for the continuous measurement of arterial oxygen in the newborn, thus allowing dangerously high and low oxygen levels to be avoided, must represent a significant advance in both physiological measurement and neonatal intensive care."}
{"id": "PMID:241438", "title": "Hydrolysis of particulate tributyrin in a fluidized lipase reactor.", "content": "Pancreatic lipase has been immobilized onto stainless steel beads by adsorption followed by crosslinking, and onto polyacrylamide by covalent bonding. The activities of the two types of immobilized enzyme toward the particulate substrate, tributyrin emulsion droplets, were determined experimentally, and rate constants based on Michaelis-Menten kinetics were calculated. The activity of the stainless steel-lipase was determined for various flow conditions and for various support sizes by the use of a differential fluidized bed recycle reactor. The rate constants calculated indicate that the experimental reaction rate is free from mass transfer influences, since the observed Michaelis constant does not vary with the fluidization velocity or with the support particle size. In addition, the Michaelis constant of the stainless steel-lipase was found to be equal to that of the free enzyme, suggesting that adsorption and subsequent crosslinking does not alter the enzyme-substrate affinity. The emulsion substrate mass transfer rates, calculated from the filtration theory, indicate that each substrate particle which contact the immobilized enzyme is hydrolyzed to a significant extent. The experimentally determined kinetic rate constants may be used directly to predict the size of integral fluidized bed reactors.", "contents": "Hydrolysis of particulate tributyrin in a fluidized lipase reactor. Pancreatic lipase has been immobilized onto stainless steel beads by adsorption followed by crosslinking, and onto polyacrylamide by covalent bonding. The activities of the two types of immobilized enzyme toward the particulate substrate, tributyrin emulsion droplets, were determined experimentally, and rate constants based on Michaelis-Menten kinetics were calculated. The activity of the stainless steel-lipase was determined for various flow conditions and for various support sizes by the use of a differential fluidized bed recycle reactor. The rate constants calculated indicate that the experimental reaction rate is free from mass transfer influences, since the observed Michaelis constant does not vary with the fluidization velocity or with the support particle size. In addition, the Michaelis constant of the stainless steel-lipase was found to be equal to that of the free enzyme, suggesting that adsorption and subsequent crosslinking does not alter the enzyme-substrate affinity. The emulsion substrate mass transfer rates, calculated from the filtration theory, indicate that each substrate particle which contact the immobilized enzyme is hydrolyzed to a significant extent. The experimentally determined kinetic rate constants may be used directly to predict the size of integral fluidized bed reactors."}
{"id": "PMID:241439", "title": "Preparation and kinetic properties of gel entrapped urate oxidase.", "content": "Urate oxidase from hog liver (urate: oxygen oxidoreductase, EC 1.7.33) has been entrapped in a crosslinked 2-hydroxyethyl methacrylate gel with a 47% retention of activity. The kinetic behavior of the gel entrapped enzyme has been studied in a slurried tank reactor using uric acid as substrate. Internal diffusion effects were found to be negligible for particle sizes below 128 mum. A threefold increase in Km (app) was observed for the 128 mum particles and attributed to diffusional effects. The pH activity profile of the gel entrapped enzyme was bell-shaped at high substrate concentration and could be fitted to a titration curve of two ionizable groups, a basic group having a pK of 7.9 and an acidic group with a pK of 11.0. The gel entrapped enzyme showed excellent stability between pH 6.5 and 10.5.", "contents": "Preparation and kinetic properties of gel entrapped urate oxidase. Urate oxidase from hog liver (urate: oxygen oxidoreductase, EC 1.7.33) has been entrapped in a crosslinked 2-hydroxyethyl methacrylate gel with a 47% retention of activity. The kinetic behavior of the gel entrapped enzyme has been studied in a slurried tank reactor using uric acid as substrate. Internal diffusion effects were found to be negligible for particle sizes below 128 mum. A threefold increase in Km (app) was observed for the 128 mum particles and attributed to diffusional effects. The pH activity profile of the gel entrapped enzyme was bell-shaped at high substrate concentration and could be fitted to a titration curve of two ionizable groups, a basic group having a pK of 7.9 and an acidic group with a pK of 11.0. The gel entrapped enzyme showed excellent stability between pH 6.5 and 10.5."}
{"id": "PMID:241440", "title": "The response of a bioelectrochemical cell with Saccharomyces cerevisiae metabolizing glucose under various fermentation conditions.", "content": "Working conditions of a biochemical fuel cell formed by an oxygen cathode and a platinum bioanode in a Saccharomyces cerevisiae suspension metabolizing glucose are described. The biocell response in terms of bioanode potential and current drainage under different fermentation conditions is reported. A kinetic equation relating the current, the number of microorganisms, and the substrate concentration is obtained. The bioanode potential corresponds to that of an oxygen concentration polarization cell.", "contents": "The response of a bioelectrochemical cell with Saccharomyces cerevisiae metabolizing glucose under various fermentation conditions. Working conditions of a biochemical fuel cell formed by an oxygen cathode and a platinum bioanode in a Saccharomyces cerevisiae suspension metabolizing glucose are described. The biocell response in terms of bioanode potential and current drainage under different fermentation conditions is reported. A kinetic equation relating the current, the number of microorganisms, and the substrate concentration is obtained. The bioanode potential corresponds to that of an oxygen concentration polarization cell."}
{"id": "PMID:241442", "title": "[Specificity of tyrosine metabolism depending on the state of melaninogenesis].", "content": "The excretion of metabolites of tyrosine (p-hydroxypyruvic acid-p-HPA, homogentisinic acid-HGA, total keto acids-TKA) and the activity of tyrosine aminotransferase of the tissues of 36 albino and 36 black rabbits was measured. The initial level of tyrosine metabolites in the urine of black and albino rabbits differed but little from one another. With the introduction of L-tyrosine, the quantity of the excreted p-HPA increased sharply, and of the HGA decreased in the albino rabbits. Among black rabbits an increase of the HGA excretion with a comparatively stable level of the excreted p-HPA was noted. Among all the tissues investigated only in the skin and the liver of albino rabbits there was a sharp increase in the initial tyrosine aminotransferase activity after the feeding of L-tyrosine, which testified to a probable adaptive synthesis of the enzyme. Analysis of the data obtained showed that tyrosine metabolism probably depended on the state of melaninogenesis.", "contents": "[Specificity of tyrosine metabolism depending on the state of melaninogenesis]. The excretion of metabolites of tyrosine (p-hydroxypyruvic acid-p-HPA, homogentisinic acid-HGA, total keto acids-TKA) and the activity of tyrosine aminotransferase of the tissues of 36 albino and 36 black rabbits was measured. The initial level of tyrosine metabolites in the urine of black and albino rabbits differed but little from one another. With the introduction of L-tyrosine, the quantity of the excreted p-HPA increased sharply, and of the HGA decreased in the albino rabbits. Among black rabbits an increase of the HGA excretion with a comparatively stable level of the excreted p-HPA was noted. Among all the tissues investigated only in the skin and the liver of albino rabbits there was a sharp increase in the initial tyrosine aminotransferase activity after the feeding of L-tyrosine, which testified to a probable adaptive synthesis of the enzyme. Analysis of the data obtained showed that tyrosine metabolism probably depended on the state of melaninogenesis."}
{"id": "PMID:241445", "title": "An electrophysiological analysis of the effects of amine-uptake blockers and alpha-adrenoceptor blockers on adrenergic neuromuscular transmission.", "content": "1 An electrophysiological study has been made of the effects of either blocking noradrenaline (NA) uptake or alpha-adrenoceptors on conduction in adrenergic preterminal axons and on NA release. 2 The excitatory junction potential (e.j.p.) evoked by a single stimulus increased slightly in duration (maximum 20%) in the presence of high concentrations of desipramine or cocaine (larger than or equal to 1 mug/ml) but there was no change in the spontaneous miniature excitatory junction potential (m.e.j.p.s); the single compound preterminal action potential was decreased in amplitude by a maximum of 10%. The e.j.p., m.e.j.p. and the terminal action potential were not altered by lower concentrations of these drugs (less than mug/ml). 3 The increased decline of the e.j.p. amplitude observed during the first few hundred impulses at high frequencies (10 Hz) in the presence of desipramine or cocaine was accompanied by a similar decline in the amplitude of the preterminal compound action potential, suggesting that the latter gave rise to the former. 4 These observations suggest that the action on post-synaptic alpha-adrenoceptors of NA released by single impulses is terminated by diffusion, and that any NA which is subsequently taken up into nerves is metabolized. 5 All the alpha-adrenoceptor blocking drugs tested reversed the normal depression in e.j.p. amplitude observed during the first few hundred impulses at high frequencies to facilitation; this was unaccompanied by any changes in the preterminal compound action potential. 6 Alpha-Adrenoceptor blocking drugs did not alter the potentiating effect which a conditioning impulse had on the amplitude of the e.j.p. evoked by a subsequent test impulse. The facilitated release of NA during trains of impulses was quantitatively predicted in terms of the addition of the individual potentiations introduced by each impulse in the train. 7 It is suggested that if there is an auto-inhibition of NA release, then it is unlikely that the pre- and post-synaptic alpha-adrenoceptors are identical.", "contents": "An electrophysiological analysis of the effects of amine-uptake blockers and alpha-adrenoceptor blockers on adrenergic neuromuscular transmission. 1 An electrophysiological study has been made of the effects of either blocking noradrenaline (NA) uptake or alpha-adrenoceptors on conduction in adrenergic preterminal axons and on NA release. 2 The excitatory junction potential (e.j.p.) evoked by a single stimulus increased slightly in duration (maximum 20%) in the presence of high concentrations of desipramine or cocaine (larger than or equal to 1 mug/ml) but there was no change in the spontaneous miniature excitatory junction potential (m.e.j.p.s); the single compound preterminal action potential was decreased in amplitude by a maximum of 10%. The e.j.p., m.e.j.p. and the terminal action potential were not altered by lower concentrations of these drugs (less than mug/ml). 3 The increased decline of the e.j.p. amplitude observed during the first few hundred impulses at high frequencies (10 Hz) in the presence of desipramine or cocaine was accompanied by a similar decline in the amplitude of the preterminal compound action potential, suggesting that the latter gave rise to the former. 4 These observations suggest that the action on post-synaptic alpha-adrenoceptors of NA released by single impulses is terminated by diffusion, and that any NA which is subsequently taken up into nerves is metabolized. 5 All the alpha-adrenoceptor blocking drugs tested reversed the normal depression in e.j.p. amplitude observed during the first few hundred impulses at high frequencies to facilitation; this was unaccompanied by any changes in the preterminal compound action potential. 6 Alpha-Adrenoceptor blocking drugs did not alter the potentiating effect which a conditioning impulse had on the amplitude of the e.j.p. evoked by a subsequent test impulse. The facilitated release of NA during trains of impulses was quantitatively predicted in terms of the addition of the individual potentiations introduced by each impulse in the train. 7 It is suggested that if there is an auto-inhibition of NA release, then it is unlikely that the pre- and post-synaptic alpha-adrenoceptors are identical."}
{"id": "PMID:241446", "title": "Epidemiology of cleft lip and palate. An attempt to rule out chance correlations.", "content": "The findings of a previous epidemiological study on oral clefts (599 children) were tested in an independent sample of 194 children, using the same source as for the previous study (Finnish Register of Congenital Malformations). Several of the earlier results--such as seasonal variation and associations between clefts and parental age, social factors, and emotional stress--were not reproduced. It is concluded that chance correlations introduce a marked problem to epidemiological studies. The findings of both studies show that there is an exceptionally high incidence of cleft palate in Finland. Significant geographical variations and associations between clefts and prematurity, threatened abortion during the first and second trimesters, maternal drug consumption during the first trimester, and influenza and fever during the first trimester were found. The possible role of these findings in the aetiology of oral clefts is discussed, and particular attention is paid to the possible teratogenicity of salicylates.", "contents": "Epidemiology of cleft lip and palate. An attempt to rule out chance correlations. The findings of a previous epidemiological study on oral clefts (599 children) were tested in an independent sample of 194 children, using the same source as for the previous study (Finnish Register of Congenital Malformations). Several of the earlier results--such as seasonal variation and associations between clefts and parental age, social factors, and emotional stress--were not reproduced. It is concluded that chance correlations introduce a marked problem to epidemiological studies. The findings of both studies show that there is an exceptionally high incidence of cleft palate in Finland. Significant geographical variations and associations between clefts and prematurity, threatened abortion during the first and second trimesters, maternal drug consumption during the first trimester, and influenza and fever during the first trimester were found. The possible role of these findings in the aetiology of oral clefts is discussed, and particular attention is paid to the possible teratogenicity of salicylates."}
{"id": "PMID:241444", "title": "Preparation and monitoring of marijuana smoke condensate samples.", "content": "The objective of this study was the production of smoke condensate from the marijuana cigarettes on schedule for the bioassay study and involved quality control on each batch of smoke condensate. Examination of the condensate production data (tables 1 and 2) reveal that it is not possible to strictly control the butt length of cigarettes when smoked on a robot smoking machine thereby accounting for some variation in the yield of the dry particulate matter and increment9-tetrahydrocannabinol. No increment8-tetrahydrocannabinol was detected in any batch of the smoke condensate. Recently, Hoffman and co-workers (13) have reported that marijuana that exhibited carcinogenic potential similar to tobacco cigarette smoke condensate in the dermal assay in mice.", "contents": "Preparation and monitoring of marijuana smoke condensate samples. The objective of this study was the production of smoke condensate from the marijuana cigarettes on schedule for the bioassay study and involved quality control on each batch of smoke condensate. Examination of the condensate production data (tables 1 and 2) reveal that it is not possible to strictly control the butt length of cigarettes when smoked on a robot smoking machine thereby accounting for some variation in the yield of the dry particulate matter and increment9-tetrahydrocannabinol. No increment8-tetrahydrocannabinol was detected in any batch of the smoke condensate. Recently, Hoffman and co-workers (13) have reported that marijuana that exhibited carcinogenic potential similar to tobacco cigarette smoke condensate in the dermal assay in mice."}
{"id": "PMID:241454", "title": "Symptomatic treatment of agoraphobia and social phobias: a follow-up study.", "content": "1. Twenty-six out of 28 out-patients with agoraphobia and social phobias who had originally been treated with phenelzine or placebo in a double-blind clinical trial were followed up for a mean period of one year. During the follow-up period patients received further pharmacotherapy or behaviour therapy, except that those patients originally receiving placebo were not allowed therapy with monoamine oxidase inhibitors. 2. Ratings of phobic and additional symptoms, social adjustment and degree of personality disorder were made after one year by one of the authors (D.S.) who had no prior knowledge of the treatment each patient had received. 3. There were no significant differences in any of the ratings between the patients of the two groups, but those originally receiving placebo had more additional treatment in the follow-up period. Patients continuing to receive phenelzine frequently experienced a return of symptoms if the drug was withdrawn before six months treatment had elapsed. 4. Degree of personality disorder showed a significant negative correlation (p = -0.6) with improvement in the phenelzine group but not in those receiving placebo originally. 5. Improvement in social adjustment items was less than improvement in symptoms at follow-up. The implications of this are discussed. 6. The results suggest that phenelzine is of comparable efficacy to other symptomatic treatments for agoraphobia and social phobias, but that it acts mainly by symptom suppression. Prolonged treatment in patients with personality disorders is not indicated, for improvement is less likely and the dangers of dependence are greater.", "contents": "Symptomatic treatment of agoraphobia and social phobias: a follow-up study. 1. Twenty-six out of 28 out-patients with agoraphobia and social phobias who had originally been treated with phenelzine or placebo in a double-blind clinical trial were followed up for a mean period of one year. During the follow-up period patients received further pharmacotherapy or behaviour therapy, except that those patients originally receiving placebo were not allowed therapy with monoamine oxidase inhibitors. 2. Ratings of phobic and additional symptoms, social adjustment and degree of personality disorder were made after one year by one of the authors (D.S.) who had no prior knowledge of the treatment each patient had received. 3. There were no significant differences in any of the ratings between the patients of the two groups, but those originally receiving placebo had more additional treatment in the follow-up period. Patients continuing to receive phenelzine frequently experienced a return of symptoms if the drug was withdrawn before six months treatment had elapsed. 4. Degree of personality disorder showed a significant negative correlation (p = -0.6) with improvement in the phenelzine group but not in those receiving placebo originally. 5. Improvement in social adjustment items was less than improvement in symptoms at follow-up. The implications of this are discussed. 6. The results suggest that phenelzine is of comparable efficacy to other symptomatic treatments for agoraphobia and social phobias, but that it acts mainly by symptom suppression. Prolonged treatment in patients with personality disorders is not indicated, for improvement is less likely and the dangers of dependence are greater."}
{"id": "PMID:241455", "title": "Treatment of chronic obsessive-compulsive neurosis by in-vivo exposure. A two-year follow-up and issues in treatment.", "content": "Twenty patients with chronic obsessive-compulsive rituals were treated in a partially controlled design by in-vivo (real life) exposure with self-imposed response prevention. Treatment included 4-12 weeks as in-patients, and lasted a mean of 23 sessions. All patients were followed-up for at least two years. No patients dropped out during the trial, though one refused domiciliary treatment after discharge. Significant improvement in compulsions was found after three weeks of real-life exposure, and continued during follow-up. At two years follow-up 14 patients were much improved, one improved and 5 unchanged; in a third year of follow-up the improved patient became symptom-free after further exposure treatment. Improvement after three weeks exposure predicted good outcome at 6 and 12 months follow-up. Muscular relaxation treatment had no significant effect on rituals. Modelling of exposure conferred no advantage over exposure alone for the group as a whole, though it may help selected patients. The role of response prevention is unknown. Patients' commitment to treatment facilitates exposure. Domiciliary treatment with involvement of family members in therapy seems crucial in some cases. Pilot group treatment of patients and families together suggests that this may be a useful adjuvant to individual treatment by increasing motivation and aiding follow-up. Compulsive slowness presents special treatment problems but can be improved by a prompting and pacing approach. The course of rituals was often independent of that of agoraphobia, marital problems and depression where these had initially coexisted with rituals. Depressive episodes were common before, during and after treatment, and required tricyclic medication. The trial sample was predominantly female but was otherwise typical of patients with compulsive rituals. Of the 125 obsessive-compulsives seen in the first author's unit over four years 96 per cent were offered behavioural or anti-depressant treatment. One quarter refused behavioural treatment after it was offered. Real-life exposure with self-imposed response prevention is usually an effective procedure for lasting reduction of chronic compulsive rituals in well motivated patients.", "contents": "Treatment of chronic obsessive-compulsive neurosis by in-vivo exposure. A two-year follow-up and issues in treatment. Twenty patients with chronic obsessive-compulsive rituals were treated in a partially controlled design by in-vivo (real life) exposure with self-imposed response prevention. Treatment included 4-12 weeks as in-patients, and lasted a mean of 23 sessions. All patients were followed-up for at least two years. No patients dropped out during the trial, though one refused domiciliary treatment after discharge. Significant improvement in compulsions was found after three weeks of real-life exposure, and continued during follow-up. At two years follow-up 14 patients were much improved, one improved and 5 unchanged; in a third year of follow-up the improved patient became symptom-free after further exposure treatment. Improvement after three weeks exposure predicted good outcome at 6 and 12 months follow-up. Muscular relaxation treatment had no significant effect on rituals. Modelling of exposure conferred no advantage over exposure alone for the group as a whole, though it may help selected patients. The role of response prevention is unknown. Patients' commitment to treatment facilitates exposure. Domiciliary treatment with involvement of family members in therapy seems crucial in some cases. Pilot group treatment of patients and families together suggests that this may be a useful adjuvant to individual treatment by increasing motivation and aiding follow-up. Compulsive slowness presents special treatment problems but can be improved by a prompting and pacing approach. The course of rituals was often independent of that of agoraphobia, marital problems and depression where these had initially coexisted with rituals. Depressive episodes were common before, during and after treatment, and required tricyclic medication. The trial sample was predominantly female but was otherwise typical of patients with compulsive rituals. Of the 125 obsessive-compulsives seen in the first author's unit over four years 96 per cent were offered behavioural or anti-depressant treatment. One quarter refused behavioural treatment after it was offered. Real-life exposure with self-imposed response prevention is usually an effective procedure for lasting reduction of chronic compulsive rituals in well motivated patients."}
{"id": "PMID:241456", "title": "The effect of an antibacterial drug on urinary calcium, magnesium and phosphorus excretion in patients with neurogenic bladder.", "content": "The effect of the simultaneous administration of hexamine mandelate and methionine on the urinary excretion of calcium, magnesium and phosphate is reported in 3 groups of paraplegic patients. Long-term therapy with G 500 increases bone loss in paralysed patients, and is contra-indicated when there is infection of the urinary tract by urea-splitting organisms.", "contents": "The effect of an antibacterial drug on urinary calcium, magnesium and phosphorus excretion in patients with neurogenic bladder. The effect of the simultaneous administration of hexamine mandelate and methionine on the urinary excretion of calcium, magnesium and phosphate is reported in 3 groups of paraplegic patients. Long-term therapy with G 500 increases bone loss in paralysed patients, and is contra-indicated when there is infection of the urinary tract by urea-splitting organisms."}
{"id": "PMID:241459", "title": "Properties of gamma-aminobutyric acid (GABA) receptor binding in rat brain synaptic membrane fractions.", "content": "The binding of GABA to crude synaptic membrane fractions of the rat central nervous system in the absence of sodium appears to involve synaptic receptor sites for GABA. The sodium-independent GABA receptor binding differs in a number of features from sodium-dependent GABA binding. In fresh tissue sodium-dependent GABA binding is about 10 times greater than sodium-independent binding, while freezing and thawing the brain membranes virtually abolishes sodium-dependent binding but increases sodium-independent GABA receptor binding about 2-fold. Both sodium-dependent and -independent GABA binding are saturable processes with dissociation constants of 1.2 muM and 0.37 muM respectively. Sodium-dependent GABA binding is much more sensitive to extremes of temperature and pH than is sodium-dependent GABA binding. In addition, regional variations in synaptosomal uptake of GABA, sodium-dependent and sodium-independent GABA binding are markedly different. Also, amino acids and drugs differ in their potencies as inhibitors of sodium-dependent and sodium-independent GABA binding, with the relative affinity of several agents for sodium-independent GABA receptor sites closely paralleling their abilities to mimic neurophysiologic effects of GABA at postsynaptic receptors. Though there are some similarities between the influence of drugs and amino acid analogues on sodium-dependent binding and synaptosomal accumulation of GABA there are also marked differences such as a much greater affinity of beta-alanine for the sodium-dependent GABA binding sites than for synaptosomal GABA uptake. This suggests that the sodium-dependent GABA binding may involve uptake sites for the GABA accumulating system of glia rather than for neuronal GABA transport.", "contents": "Properties of gamma-aminobutyric acid (GABA) receptor binding in rat brain synaptic membrane fractions. The binding of GABA to crude synaptic membrane fractions of the rat central nervous system in the absence of sodium appears to involve synaptic receptor sites for GABA. The sodium-independent GABA receptor binding differs in a number of features from sodium-dependent GABA binding. In fresh tissue sodium-dependent GABA binding is about 10 times greater than sodium-independent binding, while freezing and thawing the brain membranes virtually abolishes sodium-dependent binding but increases sodium-independent GABA receptor binding about 2-fold. Both sodium-dependent and -independent GABA binding are saturable processes with dissociation constants of 1.2 muM and 0.37 muM respectively. Sodium-dependent GABA binding is much more sensitive to extremes of temperature and pH than is sodium-dependent GABA binding. In addition, regional variations in synaptosomal uptake of GABA, sodium-dependent and sodium-independent GABA binding are markedly different. Also, amino acids and drugs differ in their potencies as inhibitors of sodium-dependent and sodium-independent GABA binding, with the relative affinity of several agents for sodium-independent GABA receptor sites closely paralleling their abilities to mimic neurophysiologic effects of GABA at postsynaptic receptors. Though there are some similarities between the influence of drugs and amino acid analogues on sodium-dependent binding and synaptosomal accumulation of GABA there are also marked differences such as a much greater affinity of beta-alanine for the sodium-dependent GABA binding sites than for synaptosomal GABA uptake. This suggests that the sodium-dependent GABA binding may involve uptake sites for the GABA accumulating system of glia rather than for neuronal GABA transport."}
{"id": "PMID:241460", "title": "Depletion of vesicles and fatigue of transmission at a vertebrate central synapse.", "content": "Synapses from Mauthner to giant fibers in the hatchetfish are chemically transmitting excitatory axo-axonic synapses located in the medulla. The synapses are 4--10 mum in diameter and easily identified for electron microscopy. Presynaptic vesicles are clustered near the contact regions and are round, clear and 40-60 nm in diameter. Stimulation of the Mauthner fiber at 10/sec for 10 min greatly reduces PSP amplitude and causes profound changes in presynaptic structures. Synaptic vesicles become few in number and there is a marked accumulation of irregular membranous structures. These changes are reversible. During the recovery period, the number of synaptic vesicles progressively increases to control values, and the number of irregular membranous structures declines. Further, stimulation during cooling induces depletion of vesicles together with a great increase in the surface area of the presynaptic membrane and in the number of coated vesicles. Internal irregular membranous structures are few. Our data provide evidence for the vesicular release of transmitter and are consistent with there being a mechanism of membrane recycling in which vesicle membrane fuses with the presynaptic membrane and is reclaimed from it by coated vesicles that then coalesce to form irregular membranous structures from which new synaptic vesicles are formed.", "contents": "Depletion of vesicles and fatigue of transmission at a vertebrate central synapse. Synapses from Mauthner to giant fibers in the hatchetfish are chemically transmitting excitatory axo-axonic synapses located in the medulla. The synapses are 4--10 mum in diameter and easily identified for electron microscopy. Presynaptic vesicles are clustered near the contact regions and are round, clear and 40-60 nm in diameter. Stimulation of the Mauthner fiber at 10/sec for 10 min greatly reduces PSP amplitude and causes profound changes in presynaptic structures. Synaptic vesicles become few in number and there is a marked accumulation of irregular membranous structures. These changes are reversible. During the recovery period, the number of synaptic vesicles progressively increases to control values, and the number of irregular membranous structures declines. Further, stimulation during cooling induces depletion of vesicles together with a great increase in the surface area of the presynaptic membrane and in the number of coated vesicles. Internal irregular membranous structures are few. Our data provide evidence for the vesicular release of transmitter and are consistent with there being a mechanism of membrane recycling in which vesicle membrane fuses with the presynaptic membrane and is reclaimed from it by coated vesicles that then coalesce to form irregular membranous structures from which new synaptic vesicles are formed."}
{"id": "PMID:241461", "title": "Fatigue and recovery of transmission at the Mauthner fiber-giant fiber synapse of the hatchetfish.", "content": "When the Mauthner fiber-giant fiber synapse of the hatchetfish is activated at gradually increasing frequencies, postsynaptic potentials (PSPs) in the giant fiber become progressively smaller, but complete failures of transmission are not observed even when PSP size is as small or smaller than miniature PSPs (mPSPs) simultaneously recorded. On the assumption of a Poisson distribution of amplitudes, calculations from the absence of failures and from variance suggest that guantum number remains at least as high as 5--10 and that quantal size is greatly reduced. During tetanic stimulation the frequency of mPSPs first increases and then decreases again, sometimes to a very low frequency. However, mPSP amplitude is reduced by no more than about 50%, which indicates that quanta giving rise to mPSPs come from a different population of vesicles than those comprising evoked PSPs. During rest following a tetanus, calculated quantal size in evoked PSPs recovers within several hundred milliseconds to mPSP size simultaneouly recorded. Most of this recovery time represents time for filling, since vesicles can be supplied at much higher rates during tetanic stimulation. After one second rest PSP amplitude exceeds threshold but recovery for later PSPs in a short train requires many minutes. The slowness of this recovery is consistent with the morphological demonstration of slow recovery of the vesicle population after depletion. These data are interpreted in terms of vesicle release, depletion and membrane recycling. Following depletion new vesicles are released after only partial filling which accounts for small quanta. Very small mPSPs are not seen because filling time is short compared to time for release as mPSPs. Since quantal size can be gradually reduced, release can interrupt filling, and filling and release sites are likely to be the same. The data in combination with the morphological observations support the hypothesis of vesicular release of transmitter and provide new evidence as to rates and sites for filling of vesicles.", "contents": "Fatigue and recovery of transmission at the Mauthner fiber-giant fiber synapse of the hatchetfish. When the Mauthner fiber-giant fiber synapse of the hatchetfish is activated at gradually increasing frequencies, postsynaptic potentials (PSPs) in the giant fiber become progressively smaller, but complete failures of transmission are not observed even when PSP size is as small or smaller than miniature PSPs (mPSPs) simultaneously recorded. On the assumption of a Poisson distribution of amplitudes, calculations from the absence of failures and from variance suggest that guantum number remains at least as high as 5--10 and that quantal size is greatly reduced. During tetanic stimulation the frequency of mPSPs first increases and then decreases again, sometimes to a very low frequency. However, mPSP amplitude is reduced by no more than about 50%, which indicates that quanta giving rise to mPSPs come from a different population of vesicles than those comprising evoked PSPs. During rest following a tetanus, calculated quantal size in evoked PSPs recovers within several hundred milliseconds to mPSP size simultaneouly recorded. Most of this recovery time represents time for filling, since vesicles can be supplied at much higher rates during tetanic stimulation. After one second rest PSP amplitude exceeds threshold but recovery for later PSPs in a short train requires many minutes. The slowness of this recovery is consistent with the morphological demonstration of slow recovery of the vesicle population after depletion. These data are interpreted in terms of vesicle release, depletion and membrane recycling. Following depletion new vesicles are released after only partial filling which accounts for small quanta. Very small mPSPs are not seen because filling time is short compared to time for release as mPSPs. Since quantal size can be gradually reduced, release can interrupt filling, and filling and release sites are likely to be the same. The data in combination with the morphological observations support the hypothesis of vesicular release of transmitter and provide new evidence as to rates and sites for filling of vesicles."}
{"id": "PMID:241463", "title": "Optimal conditions for protein synthesis in incubated slices of rat brain.", "content": "Optimal conditions for protein synthesis in incubated slices of rat brain were determined to be: thickness 0.3 mm under air (for newborn 0.4-0.6 mm) or 0.5 mm under oxygen; temperature, 35-36 degrees C; hepes (N-2-hydroxyethylpiperazine-N'-2-ethane sulfonic acid) buffer; K+, 6-8 mM; Ca2+, 2-3 mM. Though maximum incorporation was found with a Na+ concentration of 110-12- mM. Though maximum incorporation was found with a Na+ concentration of 110-120mM, this requirement appears to be partly osmotic. The Na+ concentration may be reduced to 80 mM without inhibition of incorporation provided adjustment is made for osmotic balance. Mg2+. Optimal pH was 7.2-7.4. The rate of protein synthesis in this medium is 0.08-0.09% replacement of the protein amino acid/h in slices from adults and 1.6%/h in slices from 3-day-old rats. Thus slices from adults synthesize protein at 10-20% of the in vivo rate whereas slices at 3-day-old brainincorporate amino acid at 70-80% of the in vivo rate for young rats.", "contents": "Optimal conditions for protein synthesis in incubated slices of rat brain. Optimal conditions for protein synthesis in incubated slices of rat brain were determined to be: thickness 0.3 mm under air (for newborn 0.4-0.6 mm) or 0.5 mm under oxygen; temperature, 35-36 degrees C; hepes (N-2-hydroxyethylpiperazine-N'-2-ethane sulfonic acid) buffer; K+, 6-8 mM; Ca2+, 2-3 mM. Though maximum incorporation was found with a Na+ concentration of 110-12- mM. Though maximum incorporation was found with a Na+ concentration of 110-120mM, this requirement appears to be partly osmotic. The Na+ concentration may be reduced to 80 mM without inhibition of incorporation provided adjustment is made for osmotic balance. Mg2+. Optimal pH was 7.2-7.4. The rate of protein synthesis in this medium is 0.08-0.09% replacement of the protein amino acid/h in slices from adults and 1.6%/h in slices from 3-day-old rats. Thus slices from adults synthesize protein at 10-20% of the in vivo rate whereas slices at 3-day-old brainincorporate amino acid at 70-80% of the in vivo rate for young rats."}
{"id": "PMID:241466", "title": "[Effect of cocarboxylase on hyperlactatemia and hyperpyruvicemia induced by phenformin in dogs].", "content": "In the normal anesthetized dog, a cocarboxylase perfusion considerably reduced the increase in blood lactate and pyruvate levels provoked by the intraduodenal injection of phenformin (30 mg/kg); furthermore it seems to counteract the increase of the lactates/pyruvates ratio and opposes the fall in blood pH.", "contents": "[Effect of cocarboxylase on hyperlactatemia and hyperpyruvicemia induced by phenformin in dogs]. In the normal anesthetized dog, a cocarboxylase perfusion considerably reduced the increase in blood lactate and pyruvate levels provoked by the intraduodenal injection of phenformin (30 mg/kg); furthermore it seems to counteract the increase of the lactates/pyruvates ratio and opposes the fall in blood pH."}
{"id": "PMID:241467", "title": "[Effect of repeated alcohol administration on urine secretion and antidiuretic hormone in rats].", "content": "The administration of ehtanol by gavage immediately produced a maintened hyperdiuresis, a transient decrease of urinary osmolality and antidiuretic hormone secretion, followed by increased plasmatic and urinary antidiuretic hormone concentrations. Chronic intoxication enhanced these effects probably due to central disturbance.", "contents": "[Effect of repeated alcohol administration on urine secretion and antidiuretic hormone in rats]. The administration of ehtanol by gavage immediately produced a maintened hyperdiuresis, a transient decrease of urinary osmolality and antidiuretic hormone secretion, followed by increased plasmatic and urinary antidiuretic hormone concentrations. Chronic intoxication enhanced these effects probably due to central disturbance."}
{"id": "PMID:241468", "title": "[Effect of acetazolamide on arterial blood lactate levels during recuperation in air from three days of hypercapnia].", "content": "After a three day-period of hypercapnia, carbonic anhydrase blockade by acetazolamide inhibits the development of arterial blood alcalosis during the return in normal environment, and thus eliminates the transient increase in lactacidemia due to glycolysis stimulation.", "contents": "[Effect of acetazolamide on arterial blood lactate levels during recuperation in air from three days of hypercapnia]. After a three day-period of hypercapnia, carbonic anhydrase blockade by acetazolamide inhibits the development of arterial blood alcalosis during the return in normal environment, and thus eliminates the transient increase in lactacidemia due to glycolysis stimulation."}
{"id": "PMID:241469", "title": "[Donnan equilibrium and kinetics of uric acid transport across human erythrocyte membrane].", "content": "The study of the effects of varying pH and ionic composition of external solution on the uric acid ratio (see article) for human erythrocytes at equilibrium and on its permeability constant shows that the distribution of uric acid agrees with the laws of the Gibbs-Donnan equilibrium and its passage across the human erythrocyte membrane with the law of ionic diffusion.", "contents": "[Donnan equilibrium and kinetics of uric acid transport across human erythrocyte membrane]. The study of the effects of varying pH and ionic composition of external solution on the uric acid ratio (see article) for human erythrocytes at equilibrium and on its permeability constant shows that the distribution of uric acid agrees with the laws of the Gibbs-Donnan equilibrium and its passage across the human erythrocyte membrane with the law of ionic diffusion."}
{"id": "PMID:241470", "title": "Evidence for the presence of secondary calcium phosphate in bone and its stabilization by acid production.", "content": "Calvaria from three 4-day-old chicks were incubated in a variety of buffers to study the parameters controlling the equilibration of bone with its supporting fluid environment. Strong inferential chemical evidence was obtained for the presence in viable bone of some calcium phosphate phase of high solubility apparently governed by the Ksp of CaHPO4-2H2O. In dead bone, this phase underwent spontaneous conversion to a higher Ca/P ratio. In viable bone the soluble phase appeared to be stabilized by the metabolic production of acid (lactate) as revealed by the effects of selective inhibitors.", "contents": "Evidence for the presence of secondary calcium phosphate in bone and its stabilization by acid production. Calvaria from three 4-day-old chicks were incubated in a variety of buffers to study the parameters controlling the equilibration of bone with its supporting fluid environment. Strong inferential chemical evidence was obtained for the presence in viable bone of some calcium phosphate phase of high solubility apparently governed by the Ksp of CaHPO4-2H2O. In dead bone, this phase underwent spontaneous conversion to a higher Ca/P ratio. In viable bone the soluble phase appeared to be stabilized by the metabolic production of acid (lactate) as revealed by the effects of selective inhibitors."}
{"id": "PMID:241471", "title": "Preparation and properties of matrix-supported horseradish peroxidase.", "content": "A new method of enzyme immobilization has been described using poly(4-methacryloxybenzoic acid) as the carrier. Activation of the polymer, prior to enzyme attachment, was achieved with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline. The enzyme coupling step proceeded through nucleophilic attack by the protein on a mixed carbonic anhydride. The degree of polymer activation was determined by analysis for quinoline, a by-product of the reaction. The polymer-enzyme complex was compared to the enzyme in solution in terms of pH optimum, substrate kinetics, and thermal denaturation. Potential uses of the polymerenzyme system in chemical synthesis of benzoquinone derivatives are discussed.", "contents": "Preparation and properties of matrix-supported horseradish peroxidase. A new method of enzyme immobilization has been described using poly(4-methacryloxybenzoic acid) as the carrier. Activation of the polymer, prior to enzyme attachment, was achieved with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline. The enzyme coupling step proceeded through nucleophilic attack by the protein on a mixed carbonic anhydride. The degree of polymer activation was determined by analysis for quinoline, a by-product of the reaction. The polymer-enzyme complex was compared to the enzyme in solution in terms of pH optimum, substrate kinetics, and thermal denaturation. Potential uses of the polymerenzyme system in chemical synthesis of benzoquinone derivatives are discussed."}
{"id": "PMID:241472", "title": "Phosphoenolpyruvate carboxylase of Thiobacillus thioparus. I. General properties.", "content": "Phosphoenolpyruvate (PEP) carboxylase (orthophosphate:oxalacetate carboxylase (phosphorylating), EC 4.1.1.31) was purified 19-fold from the obligate chemoautotroph, Thiobacillus thioparus. Michaelis constants for the substrates were found to be 0.44 mM for phosphoenolpyruvate, 0.89 mM for bicarbonate, and 0.37 mM for magnesium, using Tris-HC1, pH 7.3. 1-Aspartate, 1-malate, and orthophosphate were found to be inhibitors of enzyme activity, while acetyl CoA, FDP, GTP, and CDP had no effect. Dioxane greatly stimulated enzyme activity.", "contents": "Phosphoenolpyruvate carboxylase of Thiobacillus thioparus. I. General properties. Phosphoenolpyruvate (PEP) carboxylase (orthophosphate:oxalacetate carboxylase (phosphorylating), EC 4.1.1.31) was purified 19-fold from the obligate chemoautotroph, Thiobacillus thioparus. Michaelis constants for the substrates were found to be 0.44 mM for phosphoenolpyruvate, 0.89 mM for bicarbonate, and 0.37 mM for magnesium, using Tris-HC1, pH 7.3. 1-Aspartate, 1-malate, and orthophosphate were found to be inhibitors of enzyme activity, while acetyl CoA, FDP, GTP, and CDP had no effect. Dioxane greatly stimulated enzyme activity."}
{"id": "PMID:241473", "title": "Kinetic studies on soluble and insoluble urokinases.", "content": "A water-insoluble urokinase (ins-UK) was prepared by covalent coupling to an electrostatically neutral polyacrylamide derivative. The esteratic activity retained by the bound enzyme is about 70 percent of that of the soluble urokinase (UK). Comparative kinetic studies of these two forms of the enzyme were undertaken on lysine esters: N-alpha-acetyl-L-lysine-methyl ester (ALEe) and N-alpha acetylglycyl-L-lysine methyl ester (AGLMe). It was first observed that these substrates both exhibit a marked inhibitory effect toward soluble UK, whereas this phenomenon was less manifest with the insoluble form of the enzyme. Michaelis constants and maximal velocities measured at 33 degrees C, for UK and ins-UK, were identical when ALMe was used, but slightly different with AGLMe. Determination of initial velocities, at a series of pH values shows only minimal differences in the behavior of the soluble enzyme with respect to that of the insoluble form. However, over a range of temperatures, differing Km values for these two enzyme forms were obtained using AGLMe as the substrate. These last results suggest possible interactions between the substrate and the insoluble carrier of the enzyme.", "contents": "Kinetic studies on soluble and insoluble urokinases. A water-insoluble urokinase (ins-UK) was prepared by covalent coupling to an electrostatically neutral polyacrylamide derivative. The esteratic activity retained by the bound enzyme is about 70 percent of that of the soluble urokinase (UK). Comparative kinetic studies of these two forms of the enzyme were undertaken on lysine esters: N-alpha-acetyl-L-lysine-methyl ester (ALEe) and N-alpha acetylglycyl-L-lysine methyl ester (AGLMe). It was first observed that these substrates both exhibit a marked inhibitory effect toward soluble UK, whereas this phenomenon was less manifest with the insoluble form of the enzyme. Michaelis constants and maximal velocities measured at 33 degrees C, for UK and ins-UK, were identical when ALMe was used, but slightly different with AGLMe. Determination of initial velocities, at a series of pH values shows only minimal differences in the behavior of the soluble enzyme with respect to that of the insoluble form. However, over a range of temperatures, differing Km values for these two enzyme forms were obtained using AGLMe as the substrate. These last results suggest possible interactions between the substrate and the insoluble carrier of the enzyme."}
{"id": "PMID:241474", "title": "Ammoniagenesis: d-glutamyltransferase as a source of ammonia in the rat kidney.", "content": "The contribution of D-glutamyltransferase (D-GT) (EC 2.3.2.1) to total renal ammonia production was determined by employing DL-methionine-DL-sulfoximine (MSO) as an inhibitor of D-GT. Rat kidney homogenates were assayed for NH3-liberating activity under optimal D-GT or gamma-glutamyltranspeptidase (gamma-GTP) (EC 2.3.2.2) conditions. MSO inhibits only D-GT activity. The contribution of D-GT to total renal ammonia production was then evaluated in the isolated perfused rat kidney employing identical substrate (5 mM L-glutamine) and inhibitor (15 mM MSO) concentrations as employed in the homogenate study. Under these conditions, MSO inhibits 70 percent of the total ammonia production by the normal kidney; in addition, the ratio of ammonia produced per glutamine taken up rose from 1.0 to 1.8. In kidneys from chronically acidotic rats, MSO reduced total ammonia production only 35 percent while the NH3/glutamine ratio rose from 1.0 to 1.8. D-GT appears to be the predominant source of NH3 production in the normal rat kidney; gamma-GTP does not contribute significantly. The rise in the NH3/glutamine ratio after D-GT inhibition is consistent with glutamine utilization via the activated mitochondrial glutaminase (EC 3.5.1.2)-glutamate dehydrogenase (EC 1.4.1.2) pathway.", "contents": "Ammoniagenesis: d-glutamyltransferase as a source of ammonia in the rat kidney. The contribution of D-glutamyltransferase (D-GT) (EC 2.3.2.1) to total renal ammonia production was determined by employing DL-methionine-DL-sulfoximine (MSO) as an inhibitor of D-GT. Rat kidney homogenates were assayed for NH3-liberating activity under optimal D-GT or gamma-glutamyltranspeptidase (gamma-GTP) (EC 2.3.2.2) conditions. MSO inhibits only D-GT activity. The contribution of D-GT to total renal ammonia production was then evaluated in the isolated perfused rat kidney employing identical substrate (5 mM L-glutamine) and inhibitor (15 mM MSO) concentrations as employed in the homogenate study. Under these conditions, MSO inhibits 70 percent of the total ammonia production by the normal kidney; in addition, the ratio of ammonia produced per glutamine taken up rose from 1.0 to 1.8. In kidneys from chronically acidotic rats, MSO reduced total ammonia production only 35 percent while the NH3/glutamine ratio rose from 1.0 to 1.8. D-GT appears to be the predominant source of NH3 production in the normal rat kidney; gamma-GTP does not contribute significantly. The rise in the NH3/glutamine ratio after D-GT inhibition is consistent with glutamine utilization via the activated mitochondrial glutaminase (EC 3.5.1.2)-glutamate dehydrogenase (EC 1.4.1.2) pathway."}
{"id": "PMID:241475", "title": "The action of beta-galactosidase (Escherichia coli) on allolactose.", "content": "The parameters involved in the action of beta-galactosidase (EC 3.2.1.23) (Escherichia coli) on allolactose, the natural inducer of lac operon in E. coli, were studied. At low allolactose concentrations only galactose and glucose were formed, while at high allolactose concentrations transgalactolytic oligosaccharides were also produced. Detectable amounts of lactose were not formed. The V and Km values (49.6 U/mg and 0.00120 M, respectively) indicated that allolactose is as good if not a better substrate of beta-galactosidase as lactose. The pH optimum with allolactose (7.8-7.9) as well as its activation by K+ (as compared to activation by Na+) were similar to the case with lactose as substrate. The alpha-anomer of allolactose was hydrolyzed about two times as rapidly as was the beta-anomer.", "contents": "The action of beta-galactosidase (Escherichia coli) on allolactose. The parameters involved in the action of beta-galactosidase (EC 3.2.1.23) (Escherichia coli) on allolactose, the natural inducer of lac operon in E. coli, were studied. At low allolactose concentrations only galactose and glucose were formed, while at high allolactose concentrations transgalactolytic oligosaccharides were also produced. Detectable amounts of lactose were not formed. The V and Km values (49.6 U/mg and 0.00120 M, respectively) indicated that allolactose is as good if not a better substrate of beta-galactosidase as lactose. The pH optimum with allolactose (7.8-7.9) as well as its activation by K+ (as compared to activation by Na+) were similar to the case with lactose as substrate. The alpha-anomer of allolactose was hydrolyzed about two times as rapidly as was the beta-anomer."}
{"id": "PMID:241476", "title": "Purification and characterization of a trypsin inhibitor from Solanum tuberosum.", "content": "A trypsin inhibitor isolated from a potato acetone powder has been purified by affinity chromatography. This protein inhibits trypsin mole per mole. To a lesser extent it combines also with chymotrypsin and elastase. For trypsin, K1 = 8 X 10(-7) M. The inhibitor has a single polypeptide chain of 207 amino acid residues. It contains no sugar or free sulfhydryl groups. Its extinction coefficient E2801% = 10.3 and its isoelectric point is 6.9. Its molecular weight is of the order of 21 000-22000, as determined by sedimentation equilbrium, by inhibition experiment or from its amino acid composition. These same techniques, taken together with the single band observed at different pH on polyacrylamide gel electrophoresis, indicate that the protein purified is monodisperse. However, the finding of two N-terminal amino acid residues, leucine and aspartic acid, and the different stoichometry observed during the interaction of the inhibitor, either with trypsin or with chymotrypsin and elastase, raises the possibility that our preparation is contaminated by a polyvalent inhibitor not detectable by physiochemical methods.", "contents": "Purification and characterization of a trypsin inhibitor from Solanum tuberosum. A trypsin inhibitor isolated from a potato acetone powder has been purified by affinity chromatography. This protein inhibits trypsin mole per mole. To a lesser extent it combines also with chymotrypsin and elastase. For trypsin, K1 = 8 X 10(-7) M. The inhibitor has a single polypeptide chain of 207 amino acid residues. It contains no sugar or free sulfhydryl groups. Its extinction coefficient E2801% = 10.3 and its isoelectric point is 6.9. Its molecular weight is of the order of 21 000-22000, as determined by sedimentation equilbrium, by inhibition experiment or from its amino acid composition. These same techniques, taken together with the single band observed at different pH on polyacrylamide gel electrophoresis, indicate that the protein purified is monodisperse. However, the finding of two N-terminal amino acid residues, leucine and aspartic acid, and the different stoichometry observed during the interaction of the inhibitor, either with trypsin or with chymotrypsin and elastase, raises the possibility that our preparation is contaminated by a polyvalent inhibitor not detectable by physiochemical methods."}
{"id": "PMID:241477", "title": "Amino acid transport in a water-mould: the possible regulatory roles of calcium and N6-(delta2-isopentenyl)adenine.", "content": "Transport of amino acids in the water-mould Achlya is an energy-dependent process. Based on competition kinetics and studies involving the influence of pH and temperature on the initial transport rates, it was concluded that the 20 amino acids (L-isomers) commonly found in proteins were transported by more than one, possibly nine, uptake systems. This is similar to the pattern elucidated for some bacteria but unlike those uncovered for all fungi studied to date. The nine different systems elucidated are: (i) methionine, (ii) cysteine. (iii) proline, (iv) serine-threonine, (v) aspartic and glutamic  acids, (vi) glutamine and asparagine, (vii) glycine and alanine, (viii) histidine, lysine, and arginine, and (ix) phenylalanine-tyrosine-tryptophan and leucine-isoleucine-valine as two overlapping groups. Transport of all of these amino acids was inhibited by azide, cyanide, and its derivatives and 2,4-dinitrophenol. These agents normally interfere with metabolism at the level of the electron transport chain and oxidative phosphorylation. Osmotic shock treatment of the cells released, into the shock fluid, a glycopeptide that binds calcium as well as tryptophan but no other amino acid. The shocked cells are incapable of concentrating amino acids, but remain viable and reacquire this capacity when the glycopeptide is resynthesized.", "contents": "Amino acid transport in a water-mould: the possible regulatory roles of calcium and N6-(delta2-isopentenyl)adenine. Transport of amino acids in the water-mould Achlya is an energy-dependent process. Based on competition kinetics and studies involving the influence of pH and temperature on the initial transport rates, it was concluded that the 20 amino acids (L-isomers) commonly found in proteins were transported by more than one, possibly nine, uptake systems. This is similar to the pattern elucidated for some bacteria but unlike those uncovered for all fungi studied to date. The nine different systems elucidated are: (i) methionine, (ii) cysteine. (iii) proline, (iv) serine-threonine, (v) aspartic and glutamic  acids, (vi) glutamine and asparagine, (vii) glycine and alanine, (viii) histidine, lysine, and arginine, and (ix) phenylalanine-tyrosine-tryptophan and leucine-isoleucine-valine as two overlapping groups. Transport of all of these amino acids was inhibited by azide, cyanide, and its derivatives and 2,4-dinitrophenol. These agents normally interfere with metabolism at the level of the electron transport chain and oxidative phosphorylation. Osmotic shock treatment of the cells released, into the shock fluid, a glycopeptide that binds calcium as well as tryptophan but no other amino acid. The shocked cells are incapable of concentrating amino acids, but remain viable and reacquire this capacity when the glycopeptide is resynthesized."}
{"id": "PMID:241478", "title": "Sequential production of polygalacturonase, cellulase, and pectin lyase by Rhizoctonia solani.", "content": "The sequence of appearance of cell wall degrading enzymes of Rhizoctonia solani propagules was followed. Polygalacturonase (PG; EC 3.2.1.15) was induced earlier by sodium polypectate (NaPP) as compared with the induction of cellulase (Cx; EC 3.2.1.4) by carboxymethyl cellulose (CMC), cellobiose, or fibrous cellulose powder. Increasing CMC concentration to 0.5% shortened the time of Cx appearance. In Czapek medium containing citrus pectin, pectin lyase (PL; EC 4.2.2.10) was produced faster and at higher amounts than in a medium containing NaPP as the sole carbon source. PG appearance also preceded that of PL in media simultaneously supplemented with their respective inducers. NaPP, which induced production of PG, repressed Cx production. Among the Cx inducers, only CMC and cellobiose repressed PG production to any extent. At pH 6.0, either in a synthetic medium or on autoclaved bean hypocotyl segments, a delay in PG production as compared with Cx and Pl production was observed. Optimal pH levels for enzyme production and activity were 4.0 and 5.0 for PG, and 5.5 for Cx, and 8.0 and 7.5 for PL. PG was less repressed than Cx by glucose, cellobiose, and monogalacturonic acid, while PL was not affected.", "contents": "Sequential production of polygalacturonase, cellulase, and pectin lyase by Rhizoctonia solani. The sequence of appearance of cell wall degrading enzymes of Rhizoctonia solani propagules was followed. Polygalacturonase (PG; EC 3.2.1.15) was induced earlier by sodium polypectate (NaPP) as compared with the induction of cellulase (Cx; EC 3.2.1.4) by carboxymethyl cellulose (CMC), cellobiose, or fibrous cellulose powder. Increasing CMC concentration to 0.5% shortened the time of Cx appearance. In Czapek medium containing citrus pectin, pectin lyase (PL; EC 4.2.2.10) was produced faster and at higher amounts than in a medium containing NaPP as the sole carbon source. PG appearance also preceded that of PL in media simultaneously supplemented with their respective inducers. NaPP, which induced production of PG, repressed Cx production. Among the Cx inducers, only CMC and cellobiose repressed PG production to any extent. At pH 6.0, either in a synthetic medium or on autoclaved bean hypocotyl segments, a delay in PG production as compared with Cx and Pl production was observed. Optimal pH levels for enzyme production and activity were 4.0 and 5.0 for PG, and 5.5 for Cx, and 8.0 and 7.5 for PL. PG was less repressed than Cx by glucose, cellobiose, and monogalacturonic acid, while PL was not affected."}
{"id": "PMID:241479", "title": "Fungitoxicity of 1,4-naphthoquinones to Candida albicans and Trichophyton mentagrophytes.", "content": "Twenty-one substituted 1,4-naphthoquinones and five 8-quinolinols and copper(II) chelates were tested for antifungal activity against Candida albicans and Trichophyton mentagrophytes. Compounds containing electron-releasing or weak electron-withdrawing groups in the 2 and 3 positions of the 1,4-naphthoquinone ring were the most active against C. albicans at pH 7.0 in the presence of beef serum in the following order: 2-CH3O = 2,3-(CH3O)2 greater than 2-CH3 greater than 2-CH3S greater than 2-NH2 greater than 2,6-(CH3)2. For T. mentagrophytes under the same conditions the inhibitory 1,4-naphthoquinones contained the substituents 2-CH3O greater than 2,3-(CH3O)2 greater than 2-CH2S greater than 2-CH3 greater than 2-CH3(NaHSO3) greater than 2-NH2 greater than 2-C2H5S, 3-CH3 greater than 2,6-(CH3)2 greater than 2,3-CL2 greater than 5,8-(OH)2.", "contents": "Fungitoxicity of 1,4-naphthoquinones to Candida albicans and Trichophyton mentagrophytes. Twenty-one substituted 1,4-naphthoquinones and five 8-quinolinols and copper(II) chelates were tested for antifungal activity against Candida albicans and Trichophyton mentagrophytes. Compounds containing electron-releasing or weak electron-withdrawing groups in the 2 and 3 positions of the 1,4-naphthoquinone ring were the most active against C. albicans at pH 7.0 in the presence of beef serum in the following order: 2-CH3O = 2,3-(CH3O)2 greater than 2-CH3 greater than 2-CH3S greater than 2-NH2 greater than 2,6-(CH3)2. For T. mentagrophytes under the same conditions the inhibitory 1,4-naphthoquinones contained the substituents 2-CH3O greater than 2,3-(CH3O)2 greater than 2-CH2S greater than 2-CH3 greater than 2-CH3(NaHSO3) greater than 2-NH2 greater than 2-C2H5S, 3-CH3 greater than 2,6-(CH3)2 greater than 2,3-CL2 greater than 5,8-(OH)2."}
{"id": "PMID:241480", "title": "Proteolytic activity of Oidiodendron kalrai.", "content": "The physiochemical characteristics of the intracellular proteolytic enzymes of Oidiodendron kalari, a neuropathogenic fungus, were studied. The organism in the yeast phase was grown in a semisynthetic medium containing 1% tryptone, at 37 degrees C for 48 hr, on a gyrotory shaker. The crude extract was prepared by breaking the cells in a French pressure cell and the proteolytci activity was tested against biological substrates. The cell-free extract hydrolyzed casein, hemoglobin, lactalbumin, gelatin, elastin, collagen and purified rabbit renal basement membrane to various degrees. Optimal proteolytic activity was observed at pH 6 and at 32 degrees C. Calcium and EDTA did not affect the enzymatic activity; however, activity was partially inhibited by sulfhydryl-blocking agents and by heat-inactivated horse, calf, and human serum. The extract was totally inactivated by exposure to a temperature of 70 degrees C for 60 min. Storage at -76 degrees C or -15 degrees C for 6 months or at 4 degrees C for 4 weeks did not affect protease activity.", "contents": "Proteolytic activity of Oidiodendron kalrai. The physiochemical characteristics of the intracellular proteolytic enzymes of Oidiodendron kalari, a neuropathogenic fungus, were studied. The organism in the yeast phase was grown in a semisynthetic medium containing 1% tryptone, at 37 degrees C for 48 hr, on a gyrotory shaker. The crude extract was prepared by breaking the cells in a French pressure cell and the proteolytci activity was tested against biological substrates. The cell-free extract hydrolyzed casein, hemoglobin, lactalbumin, gelatin, elastin, collagen and purified rabbit renal basement membrane to various degrees. Optimal proteolytic activity was observed at pH 6 and at 32 degrees C. Calcium and EDTA did not affect the enzymatic activity; however, activity was partially inhibited by sulfhydryl-blocking agents and by heat-inactivated horse, calf, and human serum. The extract was totally inactivated by exposure to a temperature of 70 degrees C for 60 min. Storage at -76 degrees C or -15 degrees C for 6 months or at 4 degrees C for 4 weeks did not affect protease activity."}
{"id": "PMID:241481", "title": "Histochemical characterization of mucosubstances in bone and soft tissue-tumors.", "content": "The present investigation endeavors to characterize the mucosubstance content of 170 myxoid and chondromatous tumors and chordomas by histochemical methods. The results obtained using the critical electrolyte concentration (CEC) method as introduced by Scott and co-workers23,24 were compared with those obtained by staining with alcian blue and toluidine blue at different pH's with and without pretreatment with bovine testicular hyaluronidase. Tissues known biochemically to contain different heteroglycans were used as controls: synovial fluid and cock's comb (hyaluronic acid) stained with alcian blue up to a MgCl2 concentration of 0.1 M; fetal cartilage (chondroitin 4- and 6-sulphate) pulposus with notochordal remnants (keratan sulphate) up 10 1.0 M. The staining reaction of intramuscular myxoma and myxoid liposarcoma corresponded to that of synovial fluid and cock's comb (containing hyaluronic acid). Benign chondromatous tumors (osteochondroma, enchondroma, extraskeletal chondroma, chondromatosis in bursae, synovia, and tendon) as well as well-differentiated chondrosarcomas had a similar staining reaction to that of adult cartilage (containing keratan sulphate). However, the intensity of the reaction was lower in these tumors than in the adult cartilage, indicating that the keratan sulphate content of the tumors is lower. Most of the moderately well-differentiated chondrosarcomas, the poorly differentiated chondrosarcomas, and pulmonary metastases of chondrosarcoma, as well as mesenchymal chondrosarcoma and extra-skeletal chondrosarcoma possessed the same staining properties as fetal cartilage, known to contain chondroitin 4- and 6-sulphate but not keratan sulphate. A few of the moderately well-differentiated chondrosarcomas stained up to a MgCl2 concentration of 1.0 M. Three cases of poorly differentiated chondrosarcomas stained with alcian blue up to 0.35-0.45 M in the lowest differentiated areas, indicating the presence of sulphated heteroglycans, as chondroitin 4- and 6-sulphate. Most chordomas possessed the same staining properties as fetal cartilage; however, a few chordomas stained in the same way as notochordal remnants of nucleus pulposus (containing keratan sulphate), which are thought to be the origin of these tumors. The results of staining of the tumors in the present series with the Scott technique corresponds well with toluidine blue and alcian blue at different pH's with and without pretreatment of the sections with testicular hyaluronidase. Since bone and soft tissue tumors may contain varying mucosubstances depending on the tissue of origin and on differentiation, histochemical investigation of the heteroglycan content of these tumors may be a valuable diagnostic aid.", "contents": "Histochemical characterization of mucosubstances in bone and soft tissue-tumors. The present investigation endeavors to characterize the mucosubstance content of 170 myxoid and chondromatous tumors and chordomas by histochemical methods. The results obtained using the critical electrolyte concentration (CEC) method as introduced by Scott and co-workers23,24 were compared with those obtained by staining with alcian blue and toluidine blue at different pH's with and without pretreatment with bovine testicular hyaluronidase. Tissues known biochemically to contain different heteroglycans were used as controls: synovial fluid and cock's comb (hyaluronic acid) stained with alcian blue up to a MgCl2 concentration of 0.1 M; fetal cartilage (chondroitin 4- and 6-sulphate) pulposus with notochordal remnants (keratan sulphate) up 10 1.0 M. The staining reaction of intramuscular myxoma and myxoid liposarcoma corresponded to that of synovial fluid and cock's comb (containing hyaluronic acid). Benign chondromatous tumors (osteochondroma, enchondroma, extraskeletal chondroma, chondromatosis in bursae, synovia, and tendon) as well as well-differentiated chondrosarcomas had a similar staining reaction to that of adult cartilage (containing keratan sulphate). However, the intensity of the reaction was lower in these tumors than in the adult cartilage, indicating that the keratan sulphate content of the tumors is lower. Most of the moderately well-differentiated chondrosarcomas, the poorly differentiated chondrosarcomas, and pulmonary metastases of chondrosarcoma, as well as mesenchymal chondrosarcoma and extra-skeletal chondrosarcoma possessed the same staining properties as fetal cartilage, known to contain chondroitin 4- and 6-sulphate but not keratan sulphate. A few of the moderately well-differentiated chondrosarcomas stained up to a MgCl2 concentration of 1.0 M. Three cases of poorly differentiated chondrosarcomas stained with alcian blue up to 0.35-0.45 M in the lowest differentiated areas, indicating the presence of sulphated heteroglycans, as chondroitin 4- and 6-sulphate. Most chordomas possessed the same staining properties as fetal cartilage; however, a few chordomas stained in the same way as notochordal remnants of nucleus pulposus (containing keratan sulphate), which are thought to be the origin of these tumors. The results of staining of the tumors in the present series with the Scott technique corresponds well with toluidine blue and alcian blue at different pH's with and without pretreatment of the sections with testicular hyaluronidase. Since bone and soft tissue tumors may contain varying mucosubstances depending on the tissue of origin and on differentiation, histochemical investigation of the heteroglycan content of these tumors may be a valuable diagnostic aid."}
{"id": "PMID:241482", "title": "The isolation of carcinoembryonic antigen from tumor tissue at neutral pH.", "content": "Carcinoembryonic antigen (CEA) was purified from tumor tissue under mild conditions at neutral pH by a procedure that utilized affinity chromatography on concanvalin A. Further purification by gel filtration provided CEA in 10 to 20% yield and 10% purity. Antibody to this preparation was rendered specific for CEA by adsorption on a column of normal liver proteins bound to Sepharose. On reaction by immunodiffusion against a crude tumor extract, the adsorbed antibody produced two precipitin lines, of which one was relatively weak. These two precipitin lines fused completely with the two respective lines produced by antibody to perchloric acid-treated CEA. The major antigen found in crude tumor extracts and in CEA preparations purified at neutral pH was nearly undetectable in perchloric acid extracts of tumor homogenates. Further investigations showed that 60 to 70% of the CEA in crude tumor extracts and in preparations isolated at netural pH is destroyed and/or becomes insoluble acidic conditions.", "contents": "The isolation of carcinoembryonic antigen from tumor tissue at neutral pH. Carcinoembryonic antigen (CEA) was purified from tumor tissue under mild conditions at neutral pH by a procedure that utilized affinity chromatography on concanvalin A. Further purification by gel filtration provided CEA in 10 to 20% yield and 10% purity. Antibody to this preparation was rendered specific for CEA by adsorption on a column of normal liver proteins bound to Sepharose. On reaction by immunodiffusion against a crude tumor extract, the adsorbed antibody produced two precipitin lines, of which one was relatively weak. These two precipitin lines fused completely with the two respective lines produced by antibody to perchloric acid-treated CEA. The major antigen found in crude tumor extracts and in CEA preparations purified at neutral pH was nearly undetectable in perchloric acid extracts of tumor homogenates. Further investigations showed that 60 to 70% of the CEA in crude tumor extracts and in preparations isolated at netural pH is destroyed and/or becomes insoluble acidic conditions."}
{"id": "PMID:241483", "title": "Functional and structural alterations of liver ergastoplasmic membranes during DL-ethionine hepatocarcinogenesis.", "content": "Different functional and structural properties of rat liver microsomes were studied during hepatocarcinogenesis induced by 0.25% DL-ethionine. During the first to fourth months of ethionine feeding, great decreases of cytochrome P-450 content, reduced nicotinamide adenine dinucleotide phosphate-dependent lipid peroxidation, and animopyrine demethylase activity occurred. No changes in the reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase activity were observed. These functional alterations were paralleled by an increase in membrane-free  ribosomes and by changes in the relative proportions of phospholipid fatty acids in microsomes. After the end of ethionine feeding, when hyperplastic nodules and/or hepatomas were present, the above functional and structural parameters were studied in the latter tissues, as well as in surrounding nonodular liver. Decreases in cytochrome P-450 content, lipid peroxidation, and animopyrine demethylase activity were documented in hyperplastic nodules and hepatomas. In hepatomas, the alterations were more marked and decrease of reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase activity was also found. All these functional parameters were quite normal in surrounding nonnodular liver. Similarly, alterations in phospholipid fatty acid composition disappeared in surrounding nonnodular liver, but they partially persisted in both hyperplastic nodules and hepatomas. In contrast, the increase in membrane-free ribosomes also occurred in surrounding nonnodular liver, although to a lower extent than in hyperplastic nodules and hepatomas. These data are discussed in relation to the problem of the cellular precursors of hepatomas.", "contents": "Functional and structural alterations of liver ergastoplasmic membranes during DL-ethionine hepatocarcinogenesis. Different functional and structural properties of rat liver microsomes were studied during hepatocarcinogenesis induced by 0.25% DL-ethionine. During the first to fourth months of ethionine feeding, great decreases of cytochrome P-450 content, reduced nicotinamide adenine dinucleotide phosphate-dependent lipid peroxidation, and animopyrine demethylase activity occurred. No changes in the reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase activity were observed. These functional alterations were paralleled by an increase in membrane-free  ribosomes and by changes in the relative proportions of phospholipid fatty acids in microsomes. After the end of ethionine feeding, when hyperplastic nodules and/or hepatomas were present, the above functional and structural parameters were studied in the latter tissues, as well as in surrounding nonodular liver. Decreases in cytochrome P-450 content, lipid peroxidation, and animopyrine demethylase activity were documented in hyperplastic nodules and hepatomas. In hepatomas, the alterations were more marked and decrease of reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase activity was also found. All these functional parameters were quite normal in surrounding nonnodular liver. Similarly, alterations in phospholipid fatty acid composition disappeared in surrounding nonnodular liver, but they partially persisted in both hyperplastic nodules and hepatomas. In contrast, the increase in membrane-free ribosomes also occurred in surrounding nonnodular liver, although to a lower extent than in hyperplastic nodules and hepatomas. These data are discussed in relation to the problem of the cellular precursors of hepatomas."}
{"id": "PMID:241484", "title": "Imbalance of purine metabolism in hepatomas of different growth rates as expressed in behavior of glutamine-phosphoribosylpyrophosphate amidotransferase (amidophosphoribosyltransferase, EC 2.4.2.14).", "content": "The behavior of glutamine-phosphoribosylpyrophosphate amidotransferase (amidophosphoribosyltransferase, EC 2.4.2.14) was determined in normal, differentiating, and regenerating liver and in a spectrum of hepatomas of widely different growth rates. The liver and tumor enzymes were measured in 100,000 x g supernatants prepared from 20% tissue homogenates containing 0.25 M sucrose and 1 mM MgC12. Kinetic studies were carried out on the amidotransferase in the curde supernatant from liver and rapidly growing hepatoma 3924A so that under optimum standard assay conditions only the enzyme amount would be the limiting factor. The kinetic results showed that certain properties of the amidotransferase from liver and hepatoma were similar. The liver and hepatoma enzyme exhibited apparent Km's for: glutamine, 1.7 and 2.3 mM; MgC12, 0.7 and 1.1 mM, and phosphoribosylpyrophosphate. S0.5 for 0.9 and 0.4 mM, respectively...", "contents": "Imbalance of purine metabolism in hepatomas of different growth rates as expressed in behavior of glutamine-phosphoribosylpyrophosphate amidotransferase (amidophosphoribosyltransferase, EC 2.4.2.14). The behavior of glutamine-phosphoribosylpyrophosphate amidotransferase (amidophosphoribosyltransferase, EC 2.4.2.14) was determined in normal, differentiating, and regenerating liver and in a spectrum of hepatomas of widely different growth rates. The liver and tumor enzymes were measured in 100,000 x g supernatants prepared from 20% tissue homogenates containing 0.25 M sucrose and 1 mM MgC12. Kinetic studies were carried out on the amidotransferase in the curde supernatant from liver and rapidly growing hepatoma 3924A so that under optimum standard assay conditions only the enzyme amount would be the limiting factor. The kinetic results showed that certain properties of the amidotransferase from liver and hepatoma were similar. The liver and hepatoma enzyme exhibited apparent Km's for: glutamine, 1.7 and 2.3 mM; MgC12, 0.7 and 1.1 mM, and phosphoribosylpyrophosphate. S0.5 for 0.9 and 0.4 mM, respectively..."}
{"id": "PMID:241485", "title": "Microsomal metabolism of triazenylimidazoles.", "content": "The antitumor agents 5-(3,3-dimethyl-1-triazenyl)imidazole-4-carboxamide (DIC) and 5-[3,3-bis(2-chloroethyl)-1-triazenyl]imidazole-4-carboxamide (BIC) are substrates for NADPH-requiring microsomal enzymes of mouse liver. The products of DIC oxidation are 5-aminoimidazole-4-carboxamide (AIC) and formaldehyde. Those for BIC are AIC and, presumably, 2-chloroacetaldehyde. For DIC, the reaction has a pH optimum of 9.0; and the Michaelis constant (Km) is 0.25 mM. At lower pH values, the Km is not greatly increased; but there is a sharp rise in the Km values above pH 9.0. For the enzyme-catalyzed production of AIC from BIC, the pH optimum is 7.5; the Km value for BIC is 0.47 mM. Of a variety of tissues tested for enzymatic activity, only liver accomplishes the conversion of DIC and BIC to AIC. Most of the activity in the liver is located in the microsomal fraction, although detectable activity is present in washed mitochondria. For liver microsomes, the rate of reaction for BIC is greater than that for DIC, but apparently neither rate is fast enough to allow extensive metabolism of large doses of these agents.", "contents": "Microsomal metabolism of triazenylimidazoles. The antitumor agents 5-(3,3-dimethyl-1-triazenyl)imidazole-4-carboxamide (DIC) and 5-[3,3-bis(2-chloroethyl)-1-triazenyl]imidazole-4-carboxamide (BIC) are substrates for NADPH-requiring microsomal enzymes of mouse liver. The products of DIC oxidation are 5-aminoimidazole-4-carboxamide (AIC) and formaldehyde. Those for BIC are AIC and, presumably, 2-chloroacetaldehyde. For DIC, the reaction has a pH optimum of 9.0; and the Michaelis constant (Km) is 0.25 mM. At lower pH values, the Km is not greatly increased; but there is a sharp rise in the Km values above pH 9.0. For the enzyme-catalyzed production of AIC from BIC, the pH optimum is 7.5; the Km value for BIC is 0.47 mM. Of a variety of tissues tested for enzymatic activity, only liver accomplishes the conversion of DIC and BIC to AIC. Most of the activity in the liver is located in the microsomal fraction, although detectable activity is present in washed mitochondria. For liver microsomes, the rate of reaction for BIC is greater than that for DIC, but apparently neither rate is fast enough to allow extensive metabolism of large doses of these agents."}
{"id": "PMID:241486", "title": "The effect of cupric acetate on ethionine metabolism.", "content": "The addition of cupric acetate, a potent inhibitor of ethionine carcinogenesis, to a diet containing ethionine increased the ethionine toxicity. The concentration of S-adenosylethionine in liver was found to be significantly higher when compared to animals fed only ethionine in the diet. Ethionine forms a complex(es) with cupric acetate that is insoluble at a pH higher than 4; however, this complex can be solubilized at a low pH. Ethionine, if administered p.o. in the form of this complex, was absorbed from the intestinal lumen in the same order of magnitude as when administered alone; however, as the body weight increased over 200 g, the portion of absorbed ethionine decreased. The absorption of ethionine bound in the complex was completed within 16 hr compared to 2 hr for free ethionine. This time delay was accompanied by a shift in the concentration maximum of ethionine metabolities in the liver form 8 to 24 hr. When ethionine was administered alone, it was metabolized in the intestinal lumen as demonstrated by the analysis of the soluble intestinal contents; the presence of cupric acetate inhibited this process. The chromatographic analysis of ethionine metabolites in urine of rats treated by the complex revealed an increased excretion of ethionine sulfoxide and other ethionine metabolities at the expense of N-acetylethionine sulfoxide. The increased concentration of S-adenosylethionine in the liver in chronic experiments may be, at least partly, a result of a diminished capacity of the rat to detoxify (acetylate) ethionine sulfoxide, which is considered the main reserve pool of ethionine for the maintenance of a high level of S-adenosylethionine.", "contents": "The effect of cupric acetate on ethionine metabolism. The addition of cupric acetate, a potent inhibitor of ethionine carcinogenesis, to a diet containing ethionine increased the ethionine toxicity. The concentration of S-adenosylethionine in liver was found to be significantly higher when compared to animals fed only ethionine in the diet. Ethionine forms a complex(es) with cupric acetate that is insoluble at a pH higher than 4; however, this complex can be solubilized at a low pH. Ethionine, if administered p.o. in the form of this complex, was absorbed from the intestinal lumen in the same order of magnitude as when administered alone; however, as the body weight increased over 200 g, the portion of absorbed ethionine decreased. The absorption of ethionine bound in the complex was completed within 16 hr compared to 2 hr for free ethionine. This time delay was accompanied by a shift in the concentration maximum of ethionine metabolities in the liver form 8 to 24 hr. When ethionine was administered alone, it was metabolized in the intestinal lumen as demonstrated by the analysis of the soluble intestinal contents; the presence of cupric acetate inhibited this process. The chromatographic analysis of ethionine metabolites in urine of rats treated by the complex revealed an increased excretion of ethionine sulfoxide and other ethionine metabolities at the expense of N-acetylethionine sulfoxide. The increased concentration of S-adenosylethionine in the liver in chronic experiments may be, at least partly, a result of a diminished capacity of the rat to detoxify (acetylate) ethionine sulfoxide, which is considered the main reserve pool of ethionine for the maintenance of a high level of S-adenosylethionine."}
{"id": "PMID:241487", "title": "Effect of added nucleophiles and pH on alpha-D-mannosidase-catalyzed reactions.", "content": "The effect of (1) added nucleophiles, (2) the concentration of water, and (3) pH on the alpha-D-mannosidase-catalyzed hydrolysis of substituted phenyl alpha-D-mannopyranosides has been investigated.. A two-step mechanism, with formation of a mannosyl-enzyme complex, is proposed. With the phenyl alpha-D-mannopyranosides, the formation of this intermediate complex is the rate-limiting step. The activity of the enzyme is controlled by two dissociable groups having pK approximately 3 and pK approximately 6, respectively. It is proposed that one of the groups functions as a proton-donor, whereas the other group stabilizes the mannosyl-enzyme complex by ion-pair formation or covalent binding.", "contents": "Effect of added nucleophiles and pH on alpha-D-mannosidase-catalyzed reactions. The effect of (1) added nucleophiles, (2) the concentration of water, and (3) pH on the alpha-D-mannosidase-catalyzed hydrolysis of substituted phenyl alpha-D-mannopyranosides has been investigated.. A two-step mechanism, with formation of a mannosyl-enzyme complex, is proposed. With the phenyl alpha-D-mannopyranosides, the formation of this intermediate complex is the rate-limiting step. The activity of the enzyme is controlled by two dissociable groups having pK approximately 3 and pK approximately 6, respectively. It is proposed that one of the groups functions as a proton-donor, whereas the other group stabilizes the mannosyl-enzyme complex by ion-pair formation or covalent binding."}
{"id": "PMID:241508", "title": "Evidence for an increase in adrenergic nerve function in blood vessels from experimental hypertensive rabbits.", "content": "The possibility of changes in the adrenergic innervation of blood vessels in experimental hypertension was investigated by measuring arterial norepinephrine content, neuronal uptake of norepinephrine, and the neurogenic contractile response in rabbits made hypertensive by partial constriction of the abdominal aorta proximal to the kidneys. Two to 3 weeks after surgery, norepinephrine content was increased in the arteries above the ligature, where arterial blood pressure was increased, but not in the arteries below the ligature, where arterial blood pressure was normal, in the heart, or in the veins. Neuronal norepinephrine uptake per unit length of vessel and the neurogenic contractile response increased with the rise in arterial blood pressure. The neurogenic contractile response can be taken as an indication of an increase in transmitter release. The results taken together suggest an increase in the function and possibly the amount of the adrenergic neuroneal terminal in hypertension. Since the distributions of the changes in the adrenergic innervation and the increases in smooth muscle cell proliferation in hypertension are similar, these two processes may be interrelated.", "contents": "Evidence for an increase in adrenergic nerve function in blood vessels from experimental hypertensive rabbits. The possibility of changes in the adrenergic innervation of blood vessels in experimental hypertension was investigated by measuring arterial norepinephrine content, neuronal uptake of norepinephrine, and the neurogenic contractile response in rabbits made hypertensive by partial constriction of the abdominal aorta proximal to the kidneys. Two to 3 weeks after surgery, norepinephrine content was increased in the arteries above the ligature, where arterial blood pressure was increased, but not in the arteries below the ligature, where arterial blood pressure was normal, in the heart, or in the veins. Neuronal norepinephrine uptake per unit length of vessel and the neurogenic contractile response increased with the rise in arterial blood pressure. The neurogenic contractile response can be taken as an indication of an increase in transmitter release. The results taken together suggest an increase in the function and possibly the amount of the adrenergic neuroneal terminal in hypertension. Since the distributions of the changes in the adrenergic innervation and the increases in smooth muscle cell proliferation in hypertension are similar, these two processes may be interrelated."}
{"id": "PMID:241509", "title": "Colorimetric measurement of ornithine carbamoyl transferase activity in plasma, and results for a supposedly healthy population.", "content": "Determination of ornithine carbamoyl transferase (EC 2.1.3.3) activity in plasma is important for detection of liver diseases. The assay established in this paper has been made optimum. A blank is needed containing both substrates, carbamoyl phosphate and ornithine. We used a new colorimetric assay, based on a complex with a phosphoferric-antipyrine reagent and diacetyl monoxime, to measure the citrulline formed. The highly sensitive assay permits low activities to be determined accurately. Values for blood plasma from 425 supposedly healthy people, varied from 0 to 16 U/liter (95th percentile), and 27% of this population showed an activity of less than 2 mumol of citrulline formed per minute per liter, 2 U/liter being the limit of the method's sensitivity.", "contents": "Colorimetric measurement of ornithine carbamoyl transferase activity in plasma, and results for a supposedly healthy population. Determination of ornithine carbamoyl transferase (EC 2.1.3.3) activity in plasma is important for detection of liver diseases. The assay established in this paper has been made optimum. A blank is needed containing both substrates, carbamoyl phosphate and ornithine. We used a new colorimetric assay, based on a complex with a phosphoferric-antipyrine reagent and diacetyl monoxime, to measure the citrulline formed. The highly sensitive assay permits low activities to be determined accurately. Values for blood plasma from 425 supposedly healthy people, varied from 0 to 16 U/liter (95th percentile), and 27% of this population showed an activity of less than 2 mumol of citrulline formed per minute per liter, 2 U/liter being the limit of the method's sensitivity."}
{"id": "PMID:241510", "title": "Continuous determination of the oxygen dissociation curve for whole blood.", "content": "We report here the development of a new method that allows continuous determination of the oxygen dissociation curve for microsamples (600 mul) of whole blood under conditions of pH, pCO2, methemoglobin concentration, and 2,3-diphosphoglycerate content closely approaching those found in the circulatory system. The method consists of gradually oxygenating a blood sample by adding H2O2 in the presence of catalase (EC 1.11.1.6), to produce the reaction H2O2 leads to H2O + 1/2 O2. Because the total oxygen content of blood can be derived from the known rate of H202 addition and the pO2 is determined in the liquid phase by an oxygen electrode, the two functions (total O2 content) and (% oxygen saturation) vs. pO2 are simple to calculate. pCO2 and pH are controlled by adding base simultaneously with the gradual oxygenation of blood. The method described thus avoids the direct measurement of oxygen saturation of whole blood.", "contents": "Continuous determination of the oxygen dissociation curve for whole blood. We report here the development of a new method that allows continuous determination of the oxygen dissociation curve for microsamples (600 mul) of whole blood under conditions of pH, pCO2, methemoglobin concentration, and 2,3-diphosphoglycerate content closely approaching those found in the circulatory system. The method consists of gradually oxygenating a blood sample by adding H2O2 in the presence of catalase (EC 1.11.1.6), to produce the reaction H2O2 leads to H2O + 1/2 O2. Because the total oxygen content of blood can be derived from the known rate of H202 addition and the pO2 is determined in the liquid phase by an oxygen electrode, the two functions (total O2 content) and (% oxygen saturation) vs. pO2 are simple to calculate. pCO2 and pH are controlled by adding base simultaneously with the gradual oxygenation of blood. The method described thus avoids the direct measurement of oxygen saturation of whole blood."}
{"id": "PMID:241511", "title": "Hepatic synthesis of canavaninosuccinate from ureidohomoserine and aspartate, and its conversion to guanidinosuccinate.", "content": "This study continues the exploration of the mechanism for the formation of guanidinoacetate and guanidinosuccinate in the human [Clin. Chem. 21, 235 (1975)]. In this report we describe the formation of canavaninosuccinate from ureidohomoserine and aspartate by a human or bovine liver extract that had high argininosuccinate synthetase (EC 6.3.4.5) activity, and the subsequent formation of guanidinosuccinate by reductive cleavage. In the presence of ATP the optimum pH for the synthetic reaction is 8.4. This reaction can be carried out in either a tris(hydroxymethyl)aminomethane or borate buffer. Subsequent addition of dithiothreitol in the presence of Fe2+ resulted in the cleavage of some of the synthesized canavaninosuccinate to form guanidinosuccinate and homoserine. Synthesis of canavaninosuccinate was strongly inhibited by added argininosuccinate, less so by canavaninosuccinate, arginine, canavanine, glycine, or 2,3-dimercaptopropanol. The Km values for the substrates of the synthetic reaction are 3.6 X 10(-4) mol/liter for aspartate, 1.6 X 10(-3) mol/liter for ureidohomoserine, and 2.92 X 10(-5) mol/liter for ATP. These values are higher than those obtained when the synthesis of argininosuccinate was studied, except for ATP, which yielded a lower value. All of the reactions in the proposed mechanism have now been demonstrated except for the synthesis of canaline from aspartate.", "contents": "Hepatic synthesis of canavaninosuccinate from ureidohomoserine and aspartate, and its conversion to guanidinosuccinate. This study continues the exploration of the mechanism for the formation of guanidinoacetate and guanidinosuccinate in the human [Clin. Chem. 21, 235 (1975)]. In this report we describe the formation of canavaninosuccinate from ureidohomoserine and aspartate by a human or bovine liver extract that had high argininosuccinate synthetase (EC 6.3.4.5) activity, and the subsequent formation of guanidinosuccinate by reductive cleavage. In the presence of ATP the optimum pH for the synthetic reaction is 8.4. This reaction can be carried out in either a tris(hydroxymethyl)aminomethane or borate buffer. Subsequent addition of dithiothreitol in the presence of Fe2+ resulted in the cleavage of some of the synthesized canavaninosuccinate to form guanidinosuccinate and homoserine. Synthesis of canavaninosuccinate was strongly inhibited by added argininosuccinate, less so by canavaninosuccinate, arginine, canavanine, glycine, or 2,3-dimercaptopropanol. The Km values for the substrates of the synthetic reaction are 3.6 X 10(-4) mol/liter for aspartate, 1.6 X 10(-3) mol/liter for ureidohomoserine, and 2.92 X 10(-5) mol/liter for ATP. These values are higher than those obtained when the synthesis of argininosuccinate was studied, except for ATP, which yielded a lower value. All of the reactions in the proposed mechanism have now been demonstrated except for the synthesis of canaline from aspartate."}
{"id": "PMID:241512", "title": "Biochemical activity in the metastatic lesions of neuroblastoma.", "content": "Catecholamine biosynthesis in tumor cells was studied in four patients, who expired from disseminated neuroblastoma. 1. The activity of tyrosine hydroxylase was detected in tumor tissues of all but one patient. 2. Dopamine-beta-hydroxylase activity was assayabel in almost all tissues, except in the primary tumor of one patient. 3. The enzyme activities in the metastatic lesions were at the same levels in two cases, but much higher in the other two cases, as those in the primary tumours. 4. It was learned that the urinary excretion of vanilmandelic acid (VMA) and homovanillic acid (HVA) in these patients reflects the tissue levels of catecholamine synthesizing enzymes as well as the tumor mass.", "contents": "Biochemical activity in the metastatic lesions of neuroblastoma. Catecholamine biosynthesis in tumor cells was studied in four patients, who expired from disseminated neuroblastoma. 1. The activity of tyrosine hydroxylase was detected in tumor tissues of all but one patient. 2. Dopamine-beta-hydroxylase activity was assayabel in almost all tissues, except in the primary tumor of one patient. 3. The enzyme activities in the metastatic lesions were at the same levels in two cases, but much higher in the other two cases, as those in the primary tumours. 4. It was learned that the urinary excretion of vanilmandelic acid (VMA) and homovanillic acid (HVA) in these patients reflects the tissue levels of catecholamine synthesizing enzymes as well as the tumor mass."}
{"id": "PMID:241513", "title": "Fabry disease: diagnosis by alpha-galactosidase activities in tears.", "content": "The enzymatic diagnosis of hemizygotes with Fabry disease and heterozygous carriers was accomplished by the fluorometric determination of alpha-galactosidase activities in tears. Two components of total alpha-galactosidase activity were differentiated by their relative thermostabilities and by chromatography on DEAE-cellulose. The major component, alpha-galactosidase A, was thermolabile and represented approximately 90% of total activity; the remaining activity was thermostable, eluted at a slightly higher salt concentration and was designated alpha-galactosidase B. A single, symmetric pH optimum was observed for total alpha-galactosidase activities from heterozygotes and normal individuals, whereas the total activity from hemizgotes, which was about 10% of that in normal controls, had a broad pH profile, identical to those for alpha-galactosidase B activities from all individuals studied. The apparent Km values for total activities were 3.2, 4.0, and greater than 13 mM for normal individuals, heterozygotes, and hemizygotes, respectively. In contrast, apparent Km values for alpha-galactosidase B activities were greater than 13 mM for all individuals, further suggesteng that the residual activity in hemizygotes with Fabry disease represented the alpha-galactosidase B component. of the potential inhibitors studied, alpha-D-melibiose was found to competitively inhibit total alpha-galactosidase activity (Ki approximately 10 mM). These studies demonstrate that tears provide an easily obtainable source of freshly secreted enzyme for the diagnosis of hemizygotes and heterozygotes with Fabry disease and suggest that tears may be useful for the diagnosis of other inborn errors of metabolism.", "contents": "Fabry disease: diagnosis by alpha-galactosidase activities in tears. The enzymatic diagnosis of hemizygotes with Fabry disease and heterozygous carriers was accomplished by the fluorometric determination of alpha-galactosidase activities in tears. Two components of total alpha-galactosidase activity were differentiated by their relative thermostabilities and by chromatography on DEAE-cellulose. The major component, alpha-galactosidase A, was thermolabile and represented approximately 90% of total activity; the remaining activity was thermostable, eluted at a slightly higher salt concentration and was designated alpha-galactosidase B. A single, symmetric pH optimum was observed for total alpha-galactosidase activities from heterozygotes and normal individuals, whereas the total activity from hemizgotes, which was about 10% of that in normal controls, had a broad pH profile, identical to those for alpha-galactosidase B activities from all individuals studied. The apparent Km values for total activities were 3.2, 4.0, and greater than 13 mM for normal individuals, heterozygotes, and hemizygotes, respectively. In contrast, apparent Km values for alpha-galactosidase B activities were greater than 13 mM for all individuals, further suggesteng that the residual activity in hemizygotes with Fabry disease represented the alpha-galactosidase B component. of the potential inhibitors studied, alpha-D-melibiose was found to competitively inhibit total alpha-galactosidase activity (Ki approximately 10 mM). These studies demonstrate that tears provide an easily obtainable source of freshly secreted enzyme for the diagnosis of hemizygotes and heterozygotes with Fabry disease and suggest that tears may be useful for the diagnosis of other inborn errors of metabolism."}
{"id": "PMID:241514", "title": "An alternative method for the determination of uric acid in serum.", "content": "A novel fluorometric method for the determination of uric acid based on the coupled reactions of uric acid with uricase and peroxidase to form highly fluorescent 2,2'dihydroxy-3,3'-dimethoxy-biphenyl-5,5'-diacetic acid is described. The calibration curve was constructed from a series of standard uric acid solutions vs. the corresponding relative fluorescence. It was linear up to 15 mg/dl (0.9 mmol/l). The serum or plasma samples must be deproteinated with (absolute) ethanol before assay and its uric acid content can be obtained from the calibration curve. This method is rather simple, having good precision and accuracy. High level ascorbic acid in the sample falsely elevates uric acid concentration. Comparison of the results obtained on the patient sera with a colorimetric phosphotungstate method and a standard enzymatic spectrophotometric method gave coefficients of correlation of 0.908 and 0.986, respectively.", "contents": "An alternative method for the determination of uric acid in serum. A novel fluorometric method for the determination of uric acid based on the coupled reactions of uric acid with uricase and peroxidase to form highly fluorescent 2,2'dihydroxy-3,3'-dimethoxy-biphenyl-5,5'-diacetic acid is described. The calibration curve was constructed from a series of standard uric acid solutions vs. the corresponding relative fluorescence. It was linear up to 15 mg/dl (0.9 mmol/l). The serum or plasma samples must be deproteinated with (absolute) ethanol before assay and its uric acid content can be obtained from the calibration curve. This method is rather simple, having good precision and accuracy. High level ascorbic acid in the sample falsely elevates uric acid concentration. Comparison of the results obtained on the patient sera with a colorimetric phosphotungstate method and a standard enzymatic spectrophotometric method gave coefficients of correlation of 0.908 and 0.986, respectively."}
{"id": "PMID:241516", "title": "Serum ionized calcium by electrodes: new technology and methodology.", "content": "We report experience measuring serum ionized calcium (Ca2+) with new solid-state, specific calcium ion dip electrodes in a commercially available system for automated electrode measurments which permits stable measurements on thirty samples with up to six different electrodes simultaneously. The system provides electrostatic shielding, temperature regulation at 37degreeC, and adjustment of serum pH with CO2 gas, thereby making practical the use of serum standards and routine measurements on sera. When the electrodes are used with the rest of the measuring system and with serum standards, the system provides serum Ca2+ measurements with high precision (C.V. of 0.7%) and the calcium electrodes maintain good slopes for 50 to 150 hours of cumulative wet immersion. Response to new calcium activity is rapid, and wide variations in serum Ca2+ are readily measured.", "contents": "Serum ionized calcium by electrodes: new technology and methodology. We report experience measuring serum ionized calcium (Ca2+) with new solid-state, specific calcium ion dip electrodes in a commercially available system for automated electrode measurments which permits stable measurements on thirty samples with up to six different electrodes simultaneously. The system provides electrostatic shielding, temperature regulation at 37degreeC, and adjustment of serum pH with CO2 gas, thereby making practical the use of serum standards and routine measurements on sera. When the electrodes are used with the rest of the measuring system and with serum standards, the system provides serum Ca2+ measurements with high precision (C.V. of 0.7%) and the calcium electrodes maintain good slopes for 50 to 150 hours of cumulative wet immersion. Response to new calcium activity is rapid, and wide variations in serum Ca2+ are readily measured."}
{"id": "PMID:241517", "title": "A new variant of glucosephosphate isomerase deficiency (GPI-Utrecht).", "content": "A new case of glucosephosphate isomerase deficiency is described in a Dutch family. The activity of the enzyme was decreased to 20-25% of the normal value. Characterization of the defect enzyme showed a pronounced thermolability. Heating of the enzyme at 45 degrees C showed a loss of activity of 90% after one hour. The pH-optimum and the electrophoretic migration were normal. The Km-value for F-6-P, the Ki for the competitive inhibitors 2,3-DPG and 6-PG were in the normal range. The variant described here differs from all known variants. Therefore we propose to give to this new variant the name of GPI-Utrecht.", "contents": "A new variant of glucosephosphate isomerase deficiency (GPI-Utrecht). A new case of glucosephosphate isomerase deficiency is described in a Dutch family. The activity of the enzyme was decreased to 20-25% of the normal value. Characterization of the defect enzyme showed a pronounced thermolability. Heating of the enzyme at 45 degrees C showed a loss of activity of 90% after one hour. The pH-optimum and the electrophoretic migration were normal. The Km-value for F-6-P, the Ki for the competitive inhibitors 2,3-DPG and 6-PG were in the normal range. The variant described here differs from all known variants. Therefore we propose to give to this new variant the name of GPI-Utrecht."}
{"id": "PMID:241518", "title": "Studies on the stability of pancreatic enzymes in duodenal fluid to storage temperature and pH.", "content": "The effects of storage pH and temperature on pancreatic amylase, lipase and trypsin in duodenal fluid were studied. All the enzymes were most stable when stored at --20 degrees C, while the optimum storage pH was found to depend on the particular enzyme under investigation.", "contents": "Studies on the stability of pancreatic enzymes in duodenal fluid to storage temperature and pH. The effects of storage pH and temperature on pancreatic amylase, lipase and trypsin in duodenal fluid were studied. All the enzymes were most stable when stored at --20 degrees C, while the optimum storage pH was found to depend on the particular enzyme under investigation."}
{"id": "PMID:241519", "title": "Zonal ultracentrifugation of plasma lipoproteins from normal and cholestatic pigs.", "content": "The plasma lipoproteins in normal and cholestatic pigs were isolated by zonal ultracentrifugation and studied with respect to apoprotein and lipid composition. In contrast with the distribution in human plasma, only one HDL-population but two LDL-populations were demonstrated. No cholestatic lipoprotein similar to the human lipoprotein X was observed. HDL and the lighter LDL component were largely unchanged in cholestasis. The immunochemical properties were changed to some extent. Thus HDL-reacting material was found in the heavier LDL-component and VLDL after cholestasis but not before.", "contents": "Zonal ultracentrifugation of plasma lipoproteins from normal and cholestatic pigs. The plasma lipoproteins in normal and cholestatic pigs were isolated by zonal ultracentrifugation and studied with respect to apoprotein and lipid composition. In contrast with the distribution in human plasma, only one HDL-population but two LDL-populations were demonstrated. No cholestatic lipoprotein similar to the human lipoprotein X was observed. HDL and the lighter LDL component were largely unchanged in cholestasis. The immunochemical properties were changed to some extent. Thus HDL-reacting material was found in the heavier LDL-component and VLDL after cholestasis but not before."}
{"id": "PMID:241520", "title": "[A kinetic method for the determination of the activity of \"aerobic transhydrogenases\" (author's transl)].", "content": "The chromogen ABTS is the di-ammonium salt of 2,2'-azino-di[3-ethyl-benzthiazolin-sulfonic acid (6)] routinely used in the \"glucose-oxidase assay\" with the peroxidase (GOD-Perid method, Boehringer). 1. The specific property of ABTS to give a stable radical cation by oxidation with hydrogen peroxide in the presence of peroxidase was used to design a kinetic method, for enzyme-activity determinations. 2. The assay is suitable for the specific oxido-reductase using oxygen as acceptor, known also as \"aerobic transhydrogenases\" which are H2O2 formers (EC 1.-.3.-). 3. L-Amino acid: oxygen oxidoreductase (deaminating) (EC 1.4.3.2), was used throughout, being a representative model for such determinations.", "contents": "[A kinetic method for the determination of the activity of \"aerobic transhydrogenases\" (author's transl)]. The chromogen ABTS is the di-ammonium salt of 2,2'-azino-di[3-ethyl-benzthiazolin-sulfonic acid (6)] routinely used in the \"glucose-oxidase assay\" with the peroxidase (GOD-Perid method, Boehringer). 1. The specific property of ABTS to give a stable radical cation by oxidation with hydrogen peroxide in the presence of peroxidase was used to design a kinetic method, for enzyme-activity determinations. 2. The assay is suitable for the specific oxido-reductase using oxygen as acceptor, known also as \"aerobic transhydrogenases\" which are H2O2 formers (EC 1.-.3.-). 3. L-Amino acid: oxygen oxidoreductase (deaminating) (EC 1.4.3.2), was used throughout, being a representative model for such determinations."}
{"id": "PMID:241522", "title": "IgG and IgA antigens in human renal basement membranes.", "content": "Cryostat sections of fresh human kidney studied by immunofluorescence were negative for IgG, IgA, IgM, Fc and Fab fragments of IgG, and kappa and lambda light chains. All of these conjugates except anti-IgM stained glomerular basement membranes and several other connective tissues if the cryostat sections were washed in phosphate-buffered saline (PBS) before being studied. Staining was inhibited by blocking reactions as well as by fixation before washing in PBS or by washing in non-ionized or hypotonic solutions. Results of several other aspects of this reaction are also reported.", "contents": "IgG and IgA antigens in human renal basement membranes. Cryostat sections of fresh human kidney studied by immunofluorescence were negative for IgG, IgA, IgM, Fc and Fab fragments of IgG, and kappa and lambda light chains. All of these conjugates except anti-IgM stained glomerular basement membranes and several other connective tissues if the cryostat sections were washed in phosphate-buffered saline (PBS) before being studied. Staining was inhibited by blocking reactions as well as by fixation before washing in PBS or by washing in non-ionized or hypotonic solutions. Results of several other aspects of this reaction are also reported."}
{"id": "PMID:241531", "title": "Acetylation polymorphism of sulfapyridine in patients with ulcerative colitis and Crohn's disease.", "content": "Sulfapyridine (SP) is one of the main metabolites of salicylazosulfapyridine (sulfasalazine) that is used extensively in the management of inflammatory bowel disease. One hundred and twenty-two patients with ulcerative colitis or Crohn's disease were studied, including 21 new, untreated patients and 101 previously treated patients. Patients were studied for at least one year during active disease and remission. It was shown that sulfapyridine shares the same acetylation polymorphism as sulfadimidine. The acetylation capability of each patient as determined in serum and urine was constant irrespective of dose (2 to 8 gm/day) and state of disease. A single study of serum can determine acetylator phenotype in patients on sulfasalazine therapy without using any other drug for this purpose and may help ascertain dosage and assess side effects.", "contents": "Acetylation polymorphism of sulfapyridine in patients with ulcerative colitis and Crohn's disease. Sulfapyridine (SP) is one of the main metabolites of salicylazosulfapyridine (sulfasalazine) that is used extensively in the management of inflammatory bowel disease. One hundred and twenty-two patients with ulcerative colitis or Crohn's disease were studied, including 21 new, untreated patients and 101 previously treated patients. Patients were studied for at least one year during active disease and remission. It was shown that sulfapyridine shares the same acetylation polymorphism as sulfadimidine. The acetylation capability of each patient as determined in serum and urine was constant irrespective of dose (2 to 8 gm/day) and state of disease. A single study of serum can determine acetylator phenotype in patients on sulfasalazine therapy without using any other drug for this purpose and may help ascertain dosage and assess side effects."}
{"id": "PMID:241532", "title": "Salivary excretion of amobarbital in man.", "content": "The concentrations of amobarbital in saliva and serum were determined in 5 normal adults following ingestion of 120 mg of sodium amobarbital. There was excellent linear relationship between amobarbital concentrations in saliva and serum (r = 0.993); salivary levels were 36.1% of serum levels. Since the pH of saliva was generally lower than that of blood in man, the degree of ionization of amobarbital in serum and saliva had to be taken into consideration. Estimation of the protein binding of amobarbital in serum from concentrations of amobarbital in saliva and serum was in good agreement with the in vitro data of equilibrium dialysis.", "contents": "Salivary excretion of amobarbital in man. The concentrations of amobarbital in saliva and serum were determined in 5 normal adults following ingestion of 120 mg of sodium amobarbital. There was excellent linear relationship between amobarbital concentrations in saliva and serum (r = 0.993); salivary levels were 36.1% of serum levels. Since the pH of saliva was generally lower than that of blood in man, the degree of ionization of amobarbital in serum and saliva had to be taken into consideration. Estimation of the protein binding of amobarbital in serum from concentrations of amobarbital in saliva and serum was in good agreement with the in vitro data of equilibrium dialysis."}
{"id": "PMID:241533", "title": "The relationship of plasma guanethidine levels to adrenergic blockade.", "content": "Seventeen hypertensive patients receiving guanethidine for therapy were studied to determine the relationship of guanethidine plasma levels to adrenergic blockade. Plasma levels of guanethidine were measured by gas chromatography-mass spectrometry, and adrenergic blockade was defined by determining the venous reflex response to Valsalva maneuver or deep breath. A significant correlation was found between the change in the venous reflex response and the fall in mean standing pressure when guanethidine is given to patients maintained on a sodium restricted diet. A linear relationship was found between dose and plasma guanethidine concentration (p less than 0.0001), but there was a 6-fold interindividual variation in the plasma levels resulting from any given dose. Adrenergic blockade occurred when plasma levels were 8 ng/ml or higher. These results indicate that the large individual variation in dose requirements for the hypotensive effects of guanethidine most likely is not due to requirements for greatly different plasma levels of the drug; that the variation must result from pharmacokinetic determinants of differing plasma levels between individuals or from other factors, such as increased plasma volume, which maintain elevated arterial pressure in the face of adrenergic blockade.", "contents": "The relationship of plasma guanethidine levels to adrenergic blockade. Seventeen hypertensive patients receiving guanethidine for therapy were studied to determine the relationship of guanethidine plasma levels to adrenergic blockade. Plasma levels of guanethidine were measured by gas chromatography-mass spectrometry, and adrenergic blockade was defined by determining the venous reflex response to Valsalva maneuver or deep breath. A significant correlation was found between the change in the venous reflex response and the fall in mean standing pressure when guanethidine is given to patients maintained on a sodium restricted diet. A linear relationship was found between dose and plasma guanethidine concentration (p less than 0.0001), but there was a 6-fold interindividual variation in the plasma levels resulting from any given dose. Adrenergic blockade occurred when plasma levels were 8 ng/ml or higher. These results indicate that the large individual variation in dose requirements for the hypotensive effects of guanethidine most likely is not due to requirements for greatly different plasma levels of the drug; that the variation must result from pharmacokinetic determinants of differing plasma levels between individuals or from other factors, such as increased plasma volume, which maintain elevated arterial pressure in the face of adrenergic blockade."}
{"id": "PMID:241534", "title": "Effect of acidosis on patients with myocardial ischemia.", "content": "Reduction in pH is known to decrease O2 affinity (Bohr effect) and increase the rate of O2 release from blood. It provides a potential mechanism for increasing O2 transport to the myocardium. Fifteen patients with refractory, chronic angina were studied by treadmill exercise tolerance tests and whole blood-oxygen release rate measurements before and 4 days after beginning treatment with oral acetazolamide (10 to 20 mg/kg body weight). Positive treadmill exercise test or myocardial necrosis was present in each case. There was a correlation between an increased O2 release rate from blood and relief of symptoms. The major side effect in 2 patients with pathologic fatigue believed to result from acidosis. Of the 7 patients who obtained relief from angina, in each there was a 27% increase in the rate of release of O2 from their whole blood. Seven patients did not obtain relief; they showed no change in the rate of release. In the 4 patients who became worse the rate of deoxygenation decreased by 22%. All changes in deoxygenation rate coincided with the clinical findings. The treatment of ischemic heart disease with acetazolamide or other acidifying agents should not, however, be attempted until further investigation establishes their clinical value.", "contents": "Effect of acidosis on patients with myocardial ischemia. Reduction in pH is known to decrease O2 affinity (Bohr effect) and increase the rate of O2 release from blood. It provides a potential mechanism for increasing O2 transport to the myocardium. Fifteen patients with refractory, chronic angina were studied by treadmill exercise tolerance tests and whole blood-oxygen release rate measurements before and 4 days after beginning treatment with oral acetazolamide (10 to 20 mg/kg body weight). Positive treadmill exercise test or myocardial necrosis was present in each case. There was a correlation between an increased O2 release rate from blood and relief of symptoms. The major side effect in 2 patients with pathologic fatigue believed to result from acidosis. Of the 7 patients who obtained relief from angina, in each there was a 27% increase in the rate of release of O2 from their whole blood. Seven patients did not obtain relief; they showed no change in the rate of release. In the 4 patients who became worse the rate of deoxygenation decreased by 22%. All changes in deoxygenation rate coincided with the clinical findings. The treatment of ischemic heart disease with acetazolamide or other acidifying agents should not, however, be attempted until further investigation establishes their clinical value."}
{"id": "PMID:241590", "title": "Intracellular pH: measurement, control, and metabolic interrelationships.", "content": "Recent work in the field of cell pH has been characterized by many developments in techniques of measurement, by increasing knowledge of the mechanism of control of cell pH, and by progress in the establishment of relationships between cell pHi and certain areas of intermediary metabolism. Though the weight of evidence is much in favor of control cell pH by active transport of H+, the situation remains somewhat unsatisfactory due to lack of a completely adequate explanation of the work of Carter's group. The heterogeneity of cell pH raises problems in the intrepretation of hydrogen ion equilibria across cell membranes and serious difficulties in correlating changes with alterations in metabolism. To put this into perspective, however, the later difficulties are no greater than many experienced with cell constituents other than hydrogen ions.90 As in other fields, knowledge must advance by making the best of the currently available methods until such time as better techniques become available.", "contents": "Intracellular pH: measurement, control, and metabolic interrelationships. Recent work in the field of cell pH has been characterized by many developments in techniques of measurement, by increasing knowledge of the mechanism of control of cell pH, and by progress in the establishment of relationships between cell pHi and certain areas of intermediary metabolism. Though the weight of evidence is much in favor of control cell pH by active transport of H+, the situation remains somewhat unsatisfactory due to lack of a completely adequate explanation of the work of Carter's group. The heterogeneity of cell pH raises problems in the intrepretation of hydrogen ion equilibria across cell membranes and serious difficulties in correlating changes with alterations in metabolism. To put this into perspective, however, the later difficulties are no greater than many experienced with cell constituents other than hydrogen ions.90 As in other fields, knowledge must advance by making the best of the currently available methods until such time as better techniques become available."}
{"id": "PMID:241593", "title": "The chemical and biological background to alclofenac.", "content": "The essential chemistry of alclofenac is described together with a resum\u00e9 of the pharmacological and toxicological properties. Its metabolism is described and absorption and excretion commented upon. The unique character of the alclofenac molecule in relation to its active allyloxy group and its close conformational resemblance to L-tryptophan is emphasised. Particular note is made of the absence of gastro-intestinal irritation in the long-term studies in animals and in man.", "contents": "The chemical and biological background to alclofenac. The essential chemistry of alclofenac is described together with a resum\u00e9 of the pharmacological and toxicological properties. Its metabolism is described and absorption and excretion commented upon. The unique character of the alclofenac molecule in relation to its active allyloxy group and its close conformational resemblance to L-tryptophan is emphasised. Particular note is made of the absence of gastro-intestinal irritation in the long-term studies in animals and in man."}
{"id": "PMID:241591", "title": "Influence of pharmacologic agents on tissue metabolism in circulatory shock.", "content": "Our research activities have been oriented to the effect of pharmacologic agents on tissue metabolism in the low flow state of circulatory shock. Specifically, we have been most interested in the effect of glucocorticoids on cellular metabolism because these agents exert a reproducible protective effect during septic and endotoxic shock in rats and monkeys. Further, we have studied the differences between untreated animals in shock and those treated with pharmacologic agents in an attempt to determine which cellular metabolic changes are critical to survival. This paper will present our studies as well as those of other laboratories, which have defined the effects on tissue metabolism of certain pharmacologic agents: those which stimulate cyclic adenosine monophosphate (AMP) (epinephrine, norepinephrine, glucagon, and prostaglandin) and those which do not (the glucocorticoids).", "contents": "Influence of pharmacologic agents on tissue metabolism in circulatory shock. Our research activities have been oriented to the effect of pharmacologic agents on tissue metabolism in the low flow state of circulatory shock. Specifically, we have been most interested in the effect of glucocorticoids on cellular metabolism because these agents exert a reproducible protective effect during septic and endotoxic shock in rats and monkeys. Further, we have studied the differences between untreated animals in shock and those treated with pharmacologic agents in an attempt to determine which cellular metabolic changes are critical to survival. This paper will present our studies as well as those of other laboratories, which have defined the effects on tissue metabolism of certain pharmacologic agents: those which stimulate cyclic adenosine monophosphate (AMP) (epinephrine, norepinephrine, glucagon, and prostaglandin) and those which do not (the glucocorticoids)."}
{"id": "PMID:241594", "title": "A review of possible mechanisms of action of the antirheumatic drug, alclofenac.", "content": "A number and variety of hypotheses have been proposed to explain the primary mechanism of action of the antirheumatic drugs. A critical review is made of the biochemical and pharmacological parameters which, on current evidence, parallel the clinical activity of the drugs. The numerous chemical mediators of the inflammatory response are discussed, as is the possible role of endoenous anti-inflammatory substances. Particular attention is paid to the plasma protein-binding effects of antirheumatic drugs and the competitive displacement theory of drug action is examined in the light of recent work on the behaviour of L-tryptophan binding in vitro and in vivo. It is suggested that antirheumatic drugs can be differentiated by their influence on the acute-phase protein response and their effects on tryptophan binding. Clinical findings are reviewed to support the proposal that drugs such as alcofenac, which both inhibit the acute-phase response and exert prolonged influence on the binding of tryptophan to plasma proteins, reduce inflammatory activity more profoundly than those drugs which produce symptomatic relief alone. They are capable, therefore, of altering the course of the disease.", "contents": "A review of possible mechanisms of action of the antirheumatic drug, alclofenac. A number and variety of hypotheses have been proposed to explain the primary mechanism of action of the antirheumatic drugs. A critical review is made of the biochemical and pharmacological parameters which, on current evidence, parallel the clinical activity of the drugs. The numerous chemical mediators of the inflammatory response are discussed, as is the possible role of endoenous anti-inflammatory substances. Particular attention is paid to the plasma protein-binding effects of antirheumatic drugs and the competitive displacement theory of drug action is examined in the light of recent work on the behaviour of L-tryptophan binding in vitro and in vivo. It is suggested that antirheumatic drugs can be differentiated by their influence on the acute-phase protein response and their effects on tryptophan binding. Clinical findings are reviewed to support the proposal that drugs such as alcofenac, which both inhibit the acute-phase response and exert prolonged influence on the binding of tryptophan to plasma proteins, reduce inflammatory activity more profoundly than those drugs which produce symptomatic relief alone. They are capable, therefore, of altering the course of the disease."}
{"id": "PMID:241595", "title": "Simultaneous pharmacokinetics of alclofenace in plasma and synovial fluid in patients with rheumatoid arthritis.", "content": "The simultaneous pharmacokinetics of alclofenac in the plasma and synovial fluid of 10 patients with rheumatoid arthritis were studied after a single 1 g. oral dose. A gas-liquid chromatographic method was used for assaying alclofenac in both plasma and synovial fluid. Alclofenac readily appears in the plasma and synovial fluid.", "contents": "Simultaneous pharmacokinetics of alclofenace in plasma and synovial fluid in patients with rheumatoid arthritis. The simultaneous pharmacokinetics of alclofenac in the plasma and synovial fluid of 10 patients with rheumatoid arthritis were studied after a single 1 g. oral dose. A gas-liquid chromatographic method was used for assaying alclofenac in both plasma and synovial fluid. Alclofenac readily appears in the plasma and synovial fluid."}
{"id": "PMID:241596", "title": "Serum sulphydryl levels in rheumatoid patients treated with alclofenac.", "content": "Serum sulphydryl levels, which are decreased in rheumatoid patients, are increased to near normal during treatment with alclofenac. The biochemical function of the sulphydryl group and its possible pathogenic significance in rheumatoid and other auto-immune diseases are discussed.", "contents": "Serum sulphydryl levels in rheumatoid patients treated with alclofenac. Serum sulphydryl levels, which are decreased in rheumatoid patients, are increased to near normal during treatment with alclofenac. The biochemical function of the sulphydryl group and its possible pathogenic significance in rheumatoid and other auto-immune diseases are discussed."}
{"id": "PMID:241597", "title": "Clinical studies on alclofenac in the treatment of rheumatic diseases: a drug in question.", "content": "The potential advantage to patients with chronic rheumatic diseases of an effective, non-steroidal analgesic/anti-inflammatory drug which causes insignificant gastric bleeding was a decisive factor leading to the introduction of alclofenac. Short-term double-blind trials showed that alclofenac has analgesic/anti-inflammatory activities equivalent to phenylbutazone, indomethacin and aspirin, but superior to the fenemates and propionic acid derivatives. Long-term controlled studies, ranging from 5 months to 3-1/2 years and using reliable, objective measures revela, however, that patients with rheumatoid arthritis improve in functional status and graduate to less severe classes of disease activity, a phenomenon not observed with either indomethacin or aspirin administered to matched patients over the same periods of time. So far, clinical improvement on alclofenac has been matched only by treatment with gold, D-penicillamine and the immunosuppressive anti-proliferative drugs. This clinical improvement on alclofenac is reflected in haematological and serological indices, and research shows that alclofenac, like these other antirheumatoid drugs, has a pronounced effect upon the acute-phase protein response and the extent to which L-tryptophan is bound to plasma protein. The clinical data reviewed suggest that alclofenac represents an advance in the therapy of the rheumatic diseases.", "contents": "Clinical studies on alclofenac in the treatment of rheumatic diseases: a drug in question. The potential advantage to patients with chronic rheumatic diseases of an effective, non-steroidal analgesic/anti-inflammatory drug which causes insignificant gastric bleeding was a decisive factor leading to the introduction of alclofenac. Short-term double-blind trials showed that alclofenac has analgesic/anti-inflammatory activities equivalent to phenylbutazone, indomethacin and aspirin, but superior to the fenemates and propionic acid derivatives. Long-term controlled studies, ranging from 5 months to 3-1/2 years and using reliable, objective measures revela, however, that patients with rheumatoid arthritis improve in functional status and graduate to less severe classes of disease activity, a phenomenon not observed with either indomethacin or aspirin administered to matched patients over the same periods of time. So far, clinical improvement on alclofenac has been matched only by treatment with gold, D-penicillamine and the immunosuppressive anti-proliferative drugs. This clinical improvement on alclofenac is reflected in haematological and serological indices, and research shows that alclofenac, like these other antirheumatoid drugs, has a pronounced effect upon the acute-phase protein response and the extent to which L-tryptophan is bound to plasma protein. The clinical data reviewed suggest that alclofenac represents an advance in the therapy of the rheumatic diseases."}
{"id": "PMID:241598", "title": "The influence of alclofenac treatment on acute-phase proteins, plasma tryptophan, and erythrocyte sedimentation rate in patients with rheumatoid arthritis.", "content": "Alclofenac and D-penicillamine were compared under controlled, double-blind conditions in the treatment of 35 patients with active rheumatoid arthritis over a period of 26 weeks. The principal aim of the study was to investigate any relationships between changes in clinical status and changes in concentrations of three serum acute-phase proteins (fibrinogen, C-reactive protein, and haptoglobin), plasma free and protein-bound L-tryptophan, and the erythrocyte sedimentation rate. Both alclofenac and D-penicillamine were clearly effective: all patients showed steady improvement on the seven clinical indices of response employed. Drug management was easiest with alclofenac. Both drugs produced a significant reduction in acute-phase proteins, E.S.R. and protein-bound plasma tryptophan. Since it has previously been established that the course of rheumatoid arthritis is reflected in the acute-phase protein levels and the extent to which L-tryptophan is bound to plasma protein, it is suggested that drugs, such as D-penicillamin and alclofenac which profoundly affect these parameters, provide not only symptomatic relief but also possible beneficial effects on the disease process itself.", "contents": "The influence of alclofenac treatment on acute-phase proteins, plasma tryptophan, and erythrocyte sedimentation rate in patients with rheumatoid arthritis. Alclofenac and D-penicillamine were compared under controlled, double-blind conditions in the treatment of 35 patients with active rheumatoid arthritis over a period of 26 weeks. The principal aim of the study was to investigate any relationships between changes in clinical status and changes in concentrations of three serum acute-phase proteins (fibrinogen, C-reactive protein, and haptoglobin), plasma free and protein-bound L-tryptophan, and the erythrocyte sedimentation rate. Both alclofenac and D-penicillamine were clearly effective: all patients showed steady improvement on the seven clinical indices of response employed. Drug management was easiest with alclofenac. Both drugs produced a significant reduction in acute-phase proteins, E.S.R. and protein-bound plasma tryptophan. Since it has previously been established that the course of rheumatoid arthritis is reflected in the acute-phase protein levels and the extent to which L-tryptophan is bound to plasma protein, it is suggested that drugs, such as D-penicillamin and alclofenac which profoundly affect these parameters, provide not only symptomatic relief but also possible beneficial effects on the disease process itself."}
{"id": "PMID:241599", "title": "The effect of alclofenac on clinical and laboratory measures of disease activity in rheumatoid arthritis: preliminary results.", "content": "The results are presented for the first 11 patients in an on-going 3-month study of 1 g. alclofenac t.d.s. or matching placebo added to the drug regime of patients with active rheumatoid arthritis uncontrolled by full doses of analgesic/anti-inflammatory medication. Two patients dropped out, 1 due to a rash on alclofenac and 1 for incidental reasons. The numbers at this stage are too small for meaningful statistical comparison, but show an apparent trend towards clinical improvement and increase in the free:bound plasma tryptophan ratio in the alclofenac-treated patients. Three acute phase proteins, C-reactive protein, alpha-acid glycoprotein and alpha-1 antitrypsin, were measured. They did not correlate with the E.S.R. and did not appear to be useful additional predictors of disease progression. It is hoped that the results from the rest of the participants in the trial will allow more meaningful discussion of the place of these tests in the assessment of rheumatoid arthritis.", "contents": "The effect of alclofenac on clinical and laboratory measures of disease activity in rheumatoid arthritis: preliminary results. The results are presented for the first 11 patients in an on-going 3-month study of 1 g. alclofenac t.d.s. or matching placebo added to the drug regime of patients with active rheumatoid arthritis uncontrolled by full doses of analgesic/anti-inflammatory medication. Two patients dropped out, 1 due to a rash on alclofenac and 1 for incidental reasons. The numbers at this stage are too small for meaningful statistical comparison, but show an apparent trend towards clinical improvement and increase in the free:bound plasma tryptophan ratio in the alclofenac-treated patients. Three acute phase proteins, C-reactive protein, alpha-acid glycoprotein and alpha-1 antitrypsin, were measured. They did not correlate with the E.S.R. and did not appear to be useful additional predictors of disease progression. It is hoped that the results from the rest of the participants in the trial will allow more meaningful discussion of the place of these tests in the assessment of rheumatoid arthritis."}
{"id": "PMID:241600", "title": "Double-blind comparison of alclofenac and aspirin in the treatment of rheumatoid arthritis. Part II: high dosage regime for assessment of analgesic and anti-inflammatory activity.", "content": "A double-blind trial was carried out in 76 patients with active rheumatoid arthritis to compare the analgesic and anti-inflammatory activity of 3 g. alclofenac with 4.8 g. aspirin daily over a 6-week period. All patients selected showed reversible inflammatory swelling of the finger joints. Of the 60 patients successfully completing the trial, 30 were treated as out-patients and 30 patients received in-patient treatment for approximately the first 2 weeks. Both groups were analysed separately. Treatment was randomised and patients received the drugs in identical tablet form except for the last 16 patients who were transferred to capsules. Results showed that though the activity potential, morning stiffness, grip strength, joint pain and tenderness improved significantly at the end of the 6-week period, there was no statistical difference between the two drugs. However, functional capacity indicated slight superiority of alclofenac over aspirin at a low level of significance. P.I.P. joint swelling showed that both in-patients and out-patients on alclofenac improved significantly (p less than .001)compared to patients in the aspirin group. Laboratory investigations showed no difference between the two drugs as far as changes in serum proteins, serum transaminase, haemoglobin and E.S.R. levels were concerned. However, serum uric acid levels dropped significantly (.05 greater than p greater than .01) with aspirin. The incidence of side-effects was slightly higher in the aspirin group but a high incidence of skin rash (30% approx.) was recorded with alclofenac tablets. No incidence of skin rash was recorded in patients taking alclofenac capsules, but the number of patients taking capsules was too small to make any prediction. It appears from this study that in active rheumatoid arthritis the analgesic and anti-inflammatory activity of 3 g. alclofenac is equivalent to 4.8 g. aspirin, and alclofenac is superior to aspirin in reducing the inflammatory swelling of rheumatoid joints.", "contents": "Double-blind comparison of alclofenac and aspirin in the treatment of rheumatoid arthritis. Part II: high dosage regime for assessment of analgesic and anti-inflammatory activity. A double-blind trial was carried out in 76 patients with active rheumatoid arthritis to compare the analgesic and anti-inflammatory activity of 3 g. alclofenac with 4.8 g. aspirin daily over a 6-week period. All patients selected showed reversible inflammatory swelling of the finger joints. Of the 60 patients successfully completing the trial, 30 were treated as out-patients and 30 patients received in-patient treatment for approximately the first 2 weeks. Both groups were analysed separately. Treatment was randomised and patients received the drugs in identical tablet form except for the last 16 patients who were transferred to capsules. Results showed that though the activity potential, morning stiffness, grip strength, joint pain and tenderness improved significantly at the end of the 6-week period, there was no statistical difference between the two drugs. However, functional capacity indicated slight superiority of alclofenac over aspirin at a low level of significance. P.I.P. joint swelling showed that both in-patients and out-patients on alclofenac improved significantly (p less than .001)compared to patients in the aspirin group. Laboratory investigations showed no difference between the two drugs as far as changes in serum proteins, serum transaminase, haemoglobin and E.S.R. levels were concerned. However, serum uric acid levels dropped significantly (.05 greater than p greater than .01) with aspirin. The incidence of side-effects was slightly higher in the aspirin group but a high incidence of skin rash (30% approx.) was recorded with alclofenac tablets. No incidence of skin rash was recorded in patients taking alclofenac capsules, but the number of patients taking capsules was too small to make any prediction. It appears from this study that in active rheumatoid arthritis the analgesic and anti-inflammatory activity of 3 g. alclofenac is equivalent to 4.8 g. aspirin, and alclofenac is superior to aspirin in reducing the inflammatory swelling of rheumatoid joints."}
{"id": "PMID:241601", "title": "Alclofenac in ankylosing spondylitis.", "content": "Eighteen patients with definite ankylosing spondylitis were treated with 3 to 4 g. alclofenac daily for up to 8 months in an open trial against previous therapy. Therapeutic efficacy was greater than or equivalent to previous therapy in 10 of 18 patients after 1 month and 8 patients remain on alclofenac. There was a significant increase in symptoms, particularly morning stiffness after 1 month, but they tended to improve with time. Measurement of spinal movements was not found useful. Side-effects were commoner than expected but not serious. Alclofenac may prove a useful alternative drug in the management of ankylosing spondylitis and further trials are indicated.", "contents": "Alclofenac in ankylosing spondylitis. Eighteen patients with definite ankylosing spondylitis were treated with 3 to 4 g. alclofenac daily for up to 8 months in an open trial against previous therapy. Therapeutic efficacy was greater than or equivalent to previous therapy in 10 of 18 patients after 1 month and 8 patients remain on alclofenac. There was a significant increase in symptoms, particularly morning stiffness after 1 month, but they tended to improve with time. Measurement of spinal movements was not found useful. Side-effects were commoner than expected but not serious. Alclofenac may prove a useful alternative drug in the management of ankylosing spondylitis and further trials are indicated."}
{"id": "PMID:241602", "title": "A comparison of alclofenac and indomethacin in the relief of rheumatoid morning stiffness.", "content": "In a double-blind within-patient comparison of indomethacin, alclofenac and placebo taken as a single daily dose at bedtime by 29 rheumatoid out-patients, both drugs proved superior to placebo. Seventeen patients expressed a preference for indomethacin and 10 found alclofenac equal or superior in effect. The lower incidence of gastric irritation with alclofenac is confirmed and suggests its use in subjects intolerant of indomethacin.", "contents": "A comparison of alclofenac and indomethacin in the relief of rheumatoid morning stiffness. In a double-blind within-patient comparison of indomethacin, alclofenac and placebo taken as a single daily dose at bedtime by 29 rheumatoid out-patients, both drugs proved superior to placebo. Seventeen patients expressed a preference for indomethacin and 10 found alclofenac equal or superior in effect. The lower incidence of gastric irritation with alclofenac is confirmed and suggests its use in subjects intolerant of indomethacin."}
{"id": "PMID:241603", "title": "Adverse reactions to alclofenac.", "content": "By far the largest proportion of adverse reactions reported with the use of alclofenac relate to skin rashes. Estimates of the incidence of rash in approximately 1,500 patients participating in clinical trials suggest that this reaction occurred principally with the tablet (10.3%) rather than the later capsule formulation (2.1%) and since the tablet form has been discontinued there have been fewer reports. Detailed investigation of medical records and re-examination of patients developing a rash with alclofenac therapy indicate that there may be a \"cross-sensitivity\" between alclofenac and other drugs such as penicillin, gold salts and salicylates. Other adverse reactions to alclofenac, such as gastro-intestinal haemorrhage and blood disorders, have been reported only rarely.", "contents": "Adverse reactions to alclofenac. By far the largest proportion of adverse reactions reported with the use of alclofenac relate to skin rashes. Estimates of the incidence of rash in approximately 1,500 patients participating in clinical trials suggest that this reaction occurred principally with the tablet (10.3%) rather than the later capsule formulation (2.1%) and since the tablet form has been discontinued there have been fewer reports. Detailed investigation of medical records and re-examination of patients developing a rash with alclofenac therapy indicate that there may be a \"cross-sensitivity\" between alclofenac and other drugs such as penicillin, gold salts and salicylates. Other adverse reactions to alclofenac, such as gastro-intestinal haemorrhage and blood disorders, have been reported only rarely."}
{"id": "PMID:241604", "title": "Treatment of 'brain fag' syndrome.", "content": "Sixty male Nigerian students suffering from 'brain fag' syndrome who had failed to respond satisfactorily to 4 to 8 weeks' treatment with other benzodiazepines were treated with 1 to 2 mg. lorazepam t.i.d. There was marked improvement in symptoms in over 80% of the patients by the end of the second week of lorazepam treatment. Side-effects were considerably less frequent or incapacitating than with the previous therapy.", "contents": "Treatment of 'brain fag' syndrome. Sixty male Nigerian students suffering from 'brain fag' syndrome who had failed to respond satisfactorily to 4 to 8 weeks' treatment with other benzodiazepines were treated with 1 to 2 mg. lorazepam t.i.d. There was marked improvement in symptoms in over 80% of the patients by the end of the second week of lorazepam treatment. Side-effects were considerably less frequent or incapacitating than with the previous therapy."}
{"id": "PMID:241605", "title": "An unusual case of urticaria -- cause and therapy.", "content": "A case is reported of a female patient who took 140 tablets of the antihistamine, mebhydrolin ('Fabahistin'), in one day for urticaria and experienced virtually no side effects. The urticaria cleared completely when her husband, who had a cardiac condition, died suddenly.", "contents": "An unusual case of urticaria -- cause and therapy. A case is reported of a female patient who took 140 tablets of the antihistamine, mebhydrolin ('Fabahistin'), in one day for urticaria and experienced virtually no side effects. The urticaria cleared completely when her husband, who had a cardiac condition, died suddenly."}
{"id": "PMID:241610", "title": "Pneumococcal meningitis-therapeutic studies in mice.", "content": "A technique for inducing pneumococcal meningitis in mice and a description of the histopathologic changes that accompany this experimentally produced disease are provided in the present report. This infection of mice was investigated to determine whether it could serve as a suitable model for detecting agents that have potential therapeutic utility in bacterial meningitis in man. 21 antibiotics, belonging to six major classes were evaluated for efficacy in the experimental infection. The three most active agents proved to be amoxicillin, cephaloridine, and chlortetracycline. Up to this time, amoxicillin has not been commercially available as an injectable dosage form. However, in view of the compound's outstanding efficacy in the present experiments, it would be desirable to investigate its effectiveness in the naturally occurring disease in man.", "contents": "Pneumococcal meningitis-therapeutic studies in mice. A technique for inducing pneumococcal meningitis in mice and a description of the histopathologic changes that accompany this experimentally produced disease are provided in the present report. This infection of mice was investigated to determine whether it could serve as a suitable model for detecting agents that have potential therapeutic utility in bacterial meningitis in man. 21 antibiotics, belonging to six major classes were evaluated for efficacy in the experimental infection. The three most active agents proved to be amoxicillin, cephaloridine, and chlortetracycline. Up to this time, amoxicillin has not been commercially available as an injectable dosage form. However, in view of the compound's outstanding efficacy in the present experiments, it would be desirable to investigate its effectiveness in the naturally occurring disease in man."}
{"id": "PMID:241612", "title": "Hepatic microsomal metabolism of drugs during pregnancy in the rat.", "content": "A progressive depression in the in vitro hepatic microsomal enzyme metabolism of drug substrates, during pregnancy in the Wistar rat, was measured against various parameters. This depression was greatest with aniline para-hydroxylation and least with p-nitrobenzoic acid reduction. The depressed metabolism, which correlated with prolonged in vivo hexobarbital sleeping times, was paralleled by falls in hepatic microsomal cytochrome P-450 levels. There was a rapid reversal of this depression just before delivery, but these changes did not appear to be controlled by progesterone levels. The suggestion is advanced that the lower levels of hepatic microsomal enzyme activity might reflect a biological control mechanism to ensure the elevated levels of progesterone required to maintain the pregnant state. The relationship between changes in liver weight and enzyme activity was also examined as a possible explanation of the observed depression in drug metabolism during pregnancy.", "contents": "Hepatic microsomal metabolism of drugs during pregnancy in the rat. A progressive depression in the in vitro hepatic microsomal enzyme metabolism of drug substrates, during pregnancy in the Wistar rat, was measured against various parameters. This depression was greatest with aniline para-hydroxylation and least with p-nitrobenzoic acid reduction. The depressed metabolism, which correlated with prolonged in vivo hexobarbital sleeping times, was paralleled by falls in hepatic microsomal cytochrome P-450 levels. There was a rapid reversal of this depression just before delivery, but these changes did not appear to be controlled by progesterone levels. The suggestion is advanced that the lower levels of hepatic microsomal enzyme activity might reflect a biological control mechanism to ensure the elevated levels of progesterone required to maintain the pregnant state. The relationship between changes in liver weight and enzyme activity was also examined as a possible explanation of the observed depression in drug metabolism during pregnancy."}
{"id": "PMID:241613", "title": "Metabolism of debrisoquine sulfate. Identification of some urinary metabolites in rat and man.", "content": "A high proportion of an oral dose of 14C-debrisoquine sulfate is excreted in the urine by rat and man. The urinary radioactivity consists of a mixture of unchanged drug and polar, water-soluble metabolites which cannot be extracted into organic solvents. Treatment of methanolic extracts of the freeze dried urine with acetylacetone incorporates the amidino group of debrisoquine and these metabolites into a 4,6-dimethylpyrimidine ring, and yields derivatives which can be readily extracted from aqueous solution. Gas-liquid chromatographic-mass spectrometric studies of these extracts have shown that in both species: 1) the major metabolite is formed by 4-hydroxylation of debrisoquine; 2) a significant proportion of the dose is excreted as acidic metabolites, formed by opening the tetrahydroisoquinoline ring; 3) trace amounts of phenolic metabolites (5-, 6-, 7-, and 8-hydroxydebrisoquines) are also excreted.", "contents": "Metabolism of debrisoquine sulfate. Identification of some urinary metabolites in rat and man. A high proportion of an oral dose of 14C-debrisoquine sulfate is excreted in the urine by rat and man. The urinary radioactivity consists of a mixture of unchanged drug and polar, water-soluble metabolites which cannot be extracted into organic solvents. Treatment of methanolic extracts of the freeze dried urine with acetylacetone incorporates the amidino group of debrisoquine and these metabolites into a 4,6-dimethylpyrimidine ring, and yields derivatives which can be readily extracted from aqueous solution. Gas-liquid chromatographic-mass spectrometric studies of these extracts have shown that in both species: 1) the major metabolite is formed by 4-hydroxylation of debrisoquine; 2) a significant proportion of the dose is excreted as acidic metabolites, formed by opening the tetrahydroisoquinoline ring; 3) trace amounts of phenolic metabolites (5-, 6-, 7-, and 8-hydroxydebrisoquines) are also excreted."}
{"id": "PMID:241614", "title": "Metabolic activation of norethisterone (norethindrone) to an irreversibly protein-bound derivative by rat liver microsomes.", "content": "Norethisterone, specifically labeled with tritium, was incubated with hepatic microsomes of rats. About 2% of 3H radioactivity was irreversibly incorporated into the microsomal protein. This protein binding of norethisterone (about 0.7-1.6 nmol/mg of microsomal protein) was dependent on oxygen, NADPH, substrate concentration, and microsomal protein content and could be inhibited by carbon monoxide. Glutathione and other cysteine derivatives with free sulfhydryl groups diminished the microsomal protein binding diminished the microsomal protein binding as did the addition of bovine serum albumin. Norethisterone-derived radioactivity was also irreversibly bound to albumin. Solvent-extraction and charcoal-adsorption methods were employed to prove the irreversible nature of this binding. After trypsin digestion of albumin and microsomal protein loaded with norethisterone, peptides which were labeled with 3H could be isolated. To explain our results, a metabolic bioactivation of norethisterone to norethisterone-4,5-epoxide, catalyzed by the microsomal mixed-function oxidase cytochrome P-450, is proposed.", "contents": "Metabolic activation of norethisterone (norethindrone) to an irreversibly protein-bound derivative by rat liver microsomes. Norethisterone, specifically labeled with tritium, was incubated with hepatic microsomes of rats. About 2% of 3H radioactivity was irreversibly incorporated into the microsomal protein. This protein binding of norethisterone (about 0.7-1.6 nmol/mg of microsomal protein) was dependent on oxygen, NADPH, substrate concentration, and microsomal protein content and could be inhibited by carbon monoxide. Glutathione and other cysteine derivatives with free sulfhydryl groups diminished the microsomal protein binding diminished the microsomal protein binding as did the addition of bovine serum albumin. Norethisterone-derived radioactivity was also irreversibly bound to albumin. Solvent-extraction and charcoal-adsorption methods were employed to prove the irreversible nature of this binding. After trypsin digestion of albumin and microsomal protein loaded with norethisterone, peptides which were labeled with 3H could be isolated. To explain our results, a metabolic bioactivation of norethisterone to norethisterone-4,5-epoxide, catalyzed by the microsomal mixed-function oxidase cytochrome P-450, is proposed."}
{"id": "PMID:241615", "title": "Metabolism of triamterene in the rat.", "content": "The metabolism of 14C-triamterene (TA), 2,4,7-triamino-6-phenylpteridine, was investigated in rats. After administration of 14C-TA (2 mg/kg, sc), 45% and 50% of the total radioactivity was excreted in urine and feces, respectively, during 72 hr. 14C-TA and its metabolites were separated by paper chromatography and countercurrent distribution. Unchanged TA in the urine and feces accounted for 72-79% of the dose. The major metabolites in the excreted dose were free p-hydroxytriamterene (10-15%) and its conjugate (1-5%). Three hours after administration of the drug, the major metabolites were not found in gastrointestinal contents or urine when the bile duct was cannulated. They were formed in the liver and secreted in bile. A minor unidentified metabolite (2% of the dose) was also formed in the liver and excreted in urine and feces.", "contents": "Metabolism of triamterene in the rat. The metabolism of 14C-triamterene (TA), 2,4,7-triamino-6-phenylpteridine, was investigated in rats. After administration of 14C-TA (2 mg/kg, sc), 45% and 50% of the total radioactivity was excreted in urine and feces, respectively, during 72 hr. 14C-TA and its metabolites were separated by paper chromatography and countercurrent distribution. Unchanged TA in the urine and feces accounted for 72-79% of the dose. The major metabolites in the excreted dose were free p-hydroxytriamterene (10-15%) and its conjugate (1-5%). Three hours after administration of the drug, the major metabolites were not found in gastrointestinal contents or urine when the bile duct was cannulated. They were formed in the liver and secreted in bile. A minor unidentified metabolite (2% of the dose) was also formed in the liver and excreted in urine and feces."}
{"id": "PMID:241616", "title": "Biotransformation of a 1,5-benzodiazepine, triflubazam, by man.", "content": "The biotransformation of triblubazam (ORF 8063; 1-methyl-5-phenyl-7-trifluoromethyl-1H-1,5-benzodiazepin-2,4-[3H,5H]-dione) was studied in man. Seven male subjects received a chronic regimen of orally administered triblubazam for 19 consecutive days and their urine was collected for 29 days. Seven urinary metabolites were isolated by application of Sephadex LH-20 column chromatography and preparative thin-layer chromatography. Six of the purified compounds were subsequently characterized by utilizing thin-layer and gas-liquid chromatography and infrared, nuclear magnetic resonance, and mass spectrometry. The structure of a seventh metabolite was established by the use of an enzymatic assay involving catechol O-methyl-transferase. These compounds included unchanged triflubazam, the N-desmethyl catechol derivative, the 4'-hydroxyphenyl derivative, N-desmethyltriflubazam, the N-desmethyl dihydrodiol derivative, the N-desmethyl-4'-hydroxy compound, and the N-desmethyl-3'-methoxy-4'-hydroxy derivative. Unlike the situation in the metabolism of 1,4-benzodiazepines by man, no C3-hydroxylated derivatives of triflubazam were isolated. The metabolism of triblubazam by man is characterized by extensive N-demethylation, aromatic hydroxylation, aromatic O-methylation, and dihydrodiol formation.", "contents": "Biotransformation of a 1,5-benzodiazepine, triflubazam, by man. The biotransformation of triblubazam (ORF 8063; 1-methyl-5-phenyl-7-trifluoromethyl-1H-1,5-benzodiazepin-2,4-[3H,5H]-dione) was studied in man. Seven male subjects received a chronic regimen of orally administered triblubazam for 19 consecutive days and their urine was collected for 29 days. Seven urinary metabolites were isolated by application of Sephadex LH-20 column chromatography and preparative thin-layer chromatography. Six of the purified compounds were subsequently characterized by utilizing thin-layer and gas-liquid chromatography and infrared, nuclear magnetic resonance, and mass spectrometry. The structure of a seventh metabolite was established by the use of an enzymatic assay involving catechol O-methyl-transferase. These compounds included unchanged triflubazam, the N-desmethyl catechol derivative, the 4'-hydroxyphenyl derivative, N-desmethyltriflubazam, the N-desmethyl dihydrodiol derivative, the N-desmethyl-4'-hydroxy compound, and the N-desmethyl-3'-methoxy-4'-hydroxy derivative. Unlike the situation in the metabolism of 1,4-benzodiazepines by man, no C3-hydroxylated derivatives of triflubazam were isolated. The metabolism of triblubazam by man is characterized by extensive N-demethylation, aromatic hydroxylation, aromatic O-methylation, and dihydrodiol formation."}
{"id": "PMID:241617", "title": "Physiological disposition and metabolism of timolol in man and laboratory animals.", "content": "Timolol [3-(3-tert.-butylamino-2-hydroxypropoxy)-4-morpholino-1,2,5-thiadiazole], was rapidly absorbed, metabolized, and effectively excreted in man, rats, and dogs. Peak plasma levels of timolol-14C were observed in these species 1-2 hr after oral administration. Generally, less than 20% of the radioactivity was present in the plasma in the unmetabolized form. The intact drug had a plasma half-life of 28 min in the rat, 48 min in the dog, and 5.5 hr in man. After oral administration of timolol-14C to humans approximately 72% of the dose was excreted in 84 hr, with 66% in the urine and 6% in the feces. In the rat, 58% of an oral dose was excreted in the urine and 26% in the feces. The dog excreted 68% of an oral dose in the urine and 19% in feces in 72 hr. Following intravenous administration, rats excreted 50% in the urine and 28% in the feces, which suggests that extensive biliary excretion occurred. Timolol was extensively metabolized. Approximately 50% of the radioactivity was identified in dog urine as the lactic acid metabolite. An additional metabolite was tentatively identified as the 3-oxomorpholino derivative of timolol. Approximately 20% of the dose in man was excreted in the urine unchanged. Two metabolites, resulting from cleavage of the morpholine ring, were identified as 1-tert-butylamino-3-[4-(2-hydroxyethylamino)-1,2,5-thiadiazol-3-xloxyl-2-propanol, accounting for 10% of the urine radioactivity, and t-tert-butylamino-[4-(N-2-hydroxyethylglycolamido)-1,2,5-thiadiazol-3-yloxy]-2-propanol, accounting for 30%. A minor metabolite, resulting from hydroxylation of a terminal methyl group, accounted for an additional 3% of the urine radioactivity.", "contents": "Physiological disposition and metabolism of timolol in man and laboratory animals. Timolol [3-(3-tert.-butylamino-2-hydroxypropoxy)-4-morpholino-1,2,5-thiadiazole], was rapidly absorbed, metabolized, and effectively excreted in man, rats, and dogs. Peak plasma levels of timolol-14C were observed in these species 1-2 hr after oral administration. Generally, less than 20% of the radioactivity was present in the plasma in the unmetabolized form. The intact drug had a plasma half-life of 28 min in the rat, 48 min in the dog, and 5.5 hr in man. After oral administration of timolol-14C to humans approximately 72% of the dose was excreted in 84 hr, with 66% in the urine and 6% in the feces. In the rat, 58% of an oral dose was excreted in the urine and 26% in the feces. The dog excreted 68% of an oral dose in the urine and 19% in feces in 72 hr. Following intravenous administration, rats excreted 50% in the urine and 28% in the feces, which suggests that extensive biliary excretion occurred. Timolol was extensively metabolized. Approximately 50% of the radioactivity was identified in dog urine as the lactic acid metabolite. An additional metabolite was tentatively identified as the 3-oxomorpholino derivative of timolol. Approximately 20% of the dose in man was excreted in the urine unchanged. Two metabolites, resulting from cleavage of the morpholine ring, were identified as 1-tert-butylamino-3-[4-(2-hydroxyethylamino)-1,2,5-thiadiazol-3-xloxyl-2-propanol, accounting for 10% of the urine radioactivity, and t-tert-butylamino-[4-(N-2-hydroxyethylglycolamido)-1,2,5-thiadiazol-3-yloxy]-2-propanol, accounting for 30%. A minor metabolite, resulting from hydroxylation of a terminal methyl group, accounted for an additional 3% of the urine radioactivity."}
{"id": "PMID:241618", "title": "Effect of chlorination on the distribution and excretion of polychlorinated biphenyls.", "content": "The distribution and excretion of four 14C-labeled polychlorinated biphenyls (PCB), 4-chloro-, 4,4'-dichloro-, 2,4,5,2',5'-pentachloro-, and 2,4,5,2',4',5'-hexachlorobiphenyl, were studied in the rat. Total radioactivity was determined in the major organs and tissues at times varying from 15 min up to 42 days after an intravenous injection of a single 0.6-mg dose of each of the PCB's per kg. Each of the PCB's was removed rapidly from the blood and initially stored largely in the liver and muscle. The rates of the subsequent redistribution of the PCB's and their metabolites to the adipose tissue and skin and/or excretion could be related to the degree of chlorination. The relative amounts of each PCB and its metabolites in each major tissue were determined at selected time points. The percentage of the total radioactivity accounted for by metabolites of the PCB's decreased as the chlorination of the PCB's increased, but storage of metabolites did not account for a significant portion of any of the PCB doses. Excretion accounted for more than 90% of the dose of the mono-, di-, and pentachlorobiphenyls during the time period studies, whereas extrapolation of the hexachlorobiphenyl data indicated that less than 20% of the dose would ever be excreted. The rates of elimination of the PCB's were apparently determined primarily by their rates of metabolism. The effect of degree and position of chlorination on the rate of metabolism of the biphenyl molecule is discussed.", "contents": "Effect of chlorination on the distribution and excretion of polychlorinated biphenyls. The distribution and excretion of four 14C-labeled polychlorinated biphenyls (PCB), 4-chloro-, 4,4'-dichloro-, 2,4,5,2',5'-pentachloro-, and 2,4,5,2',4',5'-hexachlorobiphenyl, were studied in the rat. Total radioactivity was determined in the major organs and tissues at times varying from 15 min up to 42 days after an intravenous injection of a single 0.6-mg dose of each of the PCB's per kg. Each of the PCB's was removed rapidly from the blood and initially stored largely in the liver and muscle. The rates of the subsequent redistribution of the PCB's and their metabolites to the adipose tissue and skin and/or excretion could be related to the degree of chlorination. The relative amounts of each PCB and its metabolites in each major tissue were determined at selected time points. The percentage of the total radioactivity accounted for by metabolites of the PCB's decreased as the chlorination of the PCB's increased, but storage of metabolites did not account for a significant portion of any of the PCB doses. Excretion accounted for more than 90% of the dose of the mono-, di-, and pentachlorobiphenyls during the time period studies, whereas extrapolation of the hexachlorobiphenyl data indicated that less than 20% of the dose would ever be excreted. The rates of elimination of the PCB's were apparently determined primarily by their rates of metabolism. The effect of degree and position of chlorination on the rate of metabolism of the biphenyl molecule is discussed."}
{"id": "PMID:241619", "title": "Species differences in benzene hydroxylation to phenol by pulmonary and hepatic microsomes.", "content": "The metabolism of benzene to phenol by microsomal preparations from lung and liver has been compared in hamsters, rats, and rabbits. There were wide differences in the apparent Vmax of benzene hydroxylation among the various species and tissues and smaller differences in the apparent KM values for benzene hydroxylase. Benzene can inhibit its own metabolism in vitro when present in high concentrations. Phenol was the only metabolite of benzene identified, under the conditions of the assay, in incubation mixtures containing microsomes from lung or liver of any of the three animal species. When incubated with microsomes under the conditions used to measure benzene metabolism, phenol was further metabolized in liver but not in lung preparations. Phenol metabolism was almost completely inhibited when 11.2 mM benzene was included in the incubation mixture containing hepatic microsomes. The variation in rates of benzene hydroxylation by microsomal preparations from lungs or livers of the three animal species was similar to the variation in rates of benzypyrene hydroxylation in the same preparations.", "contents": "Species differences in benzene hydroxylation to phenol by pulmonary and hepatic microsomes. The metabolism of benzene to phenol by microsomal preparations from lung and liver has been compared in hamsters, rats, and rabbits. There were wide differences in the apparent Vmax of benzene hydroxylation among the various species and tissues and smaller differences in the apparent KM values for benzene hydroxylase. Benzene can inhibit its own metabolism in vitro when present in high concentrations. Phenol was the only metabolite of benzene identified, under the conditions of the assay, in incubation mixtures containing microsomes from lung or liver of any of the three animal species. When incubated with microsomes under the conditions used to measure benzene metabolism, phenol was further metabolized in liver but not in lung preparations. Phenol metabolism was almost completely inhibited when 11.2 mM benzene was included in the incubation mixture containing hepatic microsomes. The variation in rates of benzene hydroxylation by microsomal preparations from lungs or livers of the three animal species was similar to the variation in rates of benzypyrene hydroxylation in the same preparations."}
{"id": "PMID:241620", "title": "A study of the dynamics of imipramine accumulation in the isolated perfused rabbit lung.", "content": "An isolated perfused rabbit lung preparation (IPL) was used to study the uptake, accumulation, and efflux of the tricyclic amine imipramine (IMIP). The rate of IMIP uptake into the IPL was resolved into two exponential components (rates 1 and 2 of uptake). The initial velocities for these uptake components were linearly related to the concentration of IMIP in the perfusate (Cp). This linear relationship indicates that IMIP accumulated in the IPL by diffusion and/or binding. The steady-state accumulation of IMIP was obtained by integration of the exponential expression relating the rate of IMIP uptake to time. The amount of IMIP accumulated at steady state by rate 1 was linearly related to Cp, whereas the amount of IMIP accumulated at steady state by rate 2 was saturable with respect to Cp. These steady-state data are in agreement with the steady-state accumulation data previously reported from experiments with the recirculating blood-perfused rabbit lung. In the absence of IMIP in the perfusate. IMIP that had previously accumulated in the IPL effluxed from the lung at three rates (t1/2 = 18 sec, 58 sec, and 8.25 min), which indicates that accumulated IMIP was in at least three pools in the lung. In addition, a noneffluxable pool was detected which was not the result of irreversible binding to tissue.ated in pools 1 and 2 by rate 1 of uptake. The IMIP in pool 3 and in the noneffluxable pool was accumulated in the IPL by rate 2 of uptake. Efflux pool 3 and the IMIP accumulated at a steady state by rate 2 of uptake were resolved by a Hofstee plot into a biphasic curve indicating two types of binding sites. The noneffluxable pool of IMIP in the IPL was saturable with increasing Cp and represented approximately 30% of the IMIP accumulated by rate 2 into pool 3. Rate 2 of uptake, pool 3, and particularly the noneffluxable pool of IMIP in the IPL are possibly responsible for the accumulation and persistence of Imip in the lung as seen in whole body distribution studies. The physicochemical properties of IMIP and other compounds known to be accumulated in lung tissue are discussed in relation to the possible involvement of lung phospholipids and the compartmentalization of IMIP in the concentric lamellar organelles of the lung.", "contents": "A study of the dynamics of imipramine accumulation in the isolated perfused rabbit lung. An isolated perfused rabbit lung preparation (IPL) was used to study the uptake, accumulation, and efflux of the tricyclic amine imipramine (IMIP). The rate of IMIP uptake into the IPL was resolved into two exponential components (rates 1 and 2 of uptake). The initial velocities for these uptake components were linearly related to the concentration of IMIP in the perfusate (Cp). This linear relationship indicates that IMIP accumulated in the IPL by diffusion and/or binding. The steady-state accumulation of IMIP was obtained by integration of the exponential expression relating the rate of IMIP uptake to time. The amount of IMIP accumulated at steady state by rate 1 was linearly related to Cp, whereas the amount of IMIP accumulated at steady state by rate 2 was saturable with respect to Cp. These steady-state data are in agreement with the steady-state accumulation data previously reported from experiments with the recirculating blood-perfused rabbit lung. In the absence of IMIP in the perfusate. IMIP that had previously accumulated in the IPL effluxed from the lung at three rates (t1/2 = 18 sec, 58 sec, and 8.25 min), which indicates that accumulated IMIP was in at least three pools in the lung. In addition, a noneffluxable pool was detected which was not the result of irreversible binding to tissue.ated in pools 1 and 2 by rate 1 of uptake. The IMIP in pool 3 and in the noneffluxable pool was accumulated in the IPL by rate 2 of uptake. Efflux pool 3 and the IMIP accumulated at a steady state by rate 2 of uptake were resolved by a Hofstee plot into a biphasic curve indicating two types of binding sites. The noneffluxable pool of IMIP in the IPL was saturable with increasing Cp and represented approximately 30% of the IMIP accumulated by rate 2 into pool 3. Rate 2 of uptake, pool 3, and particularly the noneffluxable pool of IMIP in the IPL are possibly responsible for the accumulation and persistence of Imip in the lung as seen in whole body distribution studies. The physicochemical properties of IMIP and other compounds known to be accumulated in lung tissue are discussed in relation to the possible involvement of lung phospholipids and the compartmentalization of IMIP in the concentric lamellar organelles of the lung."}
{"id": "PMID:241621", "title": "Biliary excretion products of 1-[1-14C]naphthyl-N-methylcarbamate (carbaryl) in rainbow trout (Salmo gairdneri).", "content": "Uptake and metabolism of 1-naphthyl-N-methylcarbamate (carbaryl) were studied in rainbow trout (Salmo gairdneri) exposed to 14C-carbaryl in water. A high degree of biliary concentration was indicated by a 24-hr bile to water 14C ratio of nearly 1000:1. Four 14C-labeled compounds were purified from bile and two have been identified with reasonable certainty as unchanged carbaryl and 1-naphthol glucuronide. 5,6-Dihydro-5,6-dihydroxy-1-naphthyl-N-methylcarbamate was tentatively identified by thin-layer chromatography. The results indicate that carbaryl can be metabolized in rainbow trout via pathways similar to those reported in mammals and that bile analysis may be helpful in monitoring fish for exposure to this compound.", "contents": "Biliary excretion products of 1-[1-14C]naphthyl-N-methylcarbamate (carbaryl) in rainbow trout (Salmo gairdneri). Uptake and metabolism of 1-naphthyl-N-methylcarbamate (carbaryl) were studied in rainbow trout (Salmo gairdneri) exposed to 14C-carbaryl in water. A high degree of biliary concentration was indicated by a 24-hr bile to water 14C ratio of nearly 1000:1. Four 14C-labeled compounds were purified from bile and two have been identified with reasonable certainty as unchanged carbaryl and 1-naphthol glucuronide. 5,6-Dihydro-5,6-dihydroxy-1-naphthyl-N-methylcarbamate was tentatively identified by thin-layer chromatography. The results indicate that carbaryl can be metabolized in rainbow trout via pathways similar to those reported in mammals and that bile analysis may be helpful in monitoring fish for exposure to this compound."}
{"id": "PMID:241622", "title": "Effect of 3-methylcholanthrene pretreatment on glucuronidation and sulfation in perfused rat liver.", "content": "The metabolism of p-nitro[14C]phenol (PNP) was studied in perfused rat liver. Metabolites were identified in perfusate and bile. The perfusion system containing 0.5 mM PNP, at the start, converted the phenol within 2 hr to p-nitrophenyl glucuronide (PNPGA), 31.4% in perfusate and 21% in bile; p-nitrophenyl sulfate (PNPS), 22% in perfusate; and p-nitrophenyl glucoside (PNPG), between 2 and 4% perfusate. Biliary excretion of PNPS and PNPG accounted for less than 2% of PNP. An apparent maximal rate of PNPGA synthesis by the perfused liver, estimated from the rates of appearance of PNPGA in perfusate and bile, corresponded well to the glucuronyl-transferase activities determined in \"native\" liver homogenates. Sulfation of PNP in the perfused liver exhibited two apparent maximal rates of synthesis, as determined from the rates of appearance of metabolite in the perfusate. A slower rate (R1) occurred when PNP concentration was between 0.13 and 0.5 mM, and a faster rate (R2) when PNP was approximately between 0.025 and 0.13 mM in the perfusate. Possible significance of these findings is discussed. Pretreatment of rats with 3-methylcholanthrene (3MC) increased the apparent maximal rate of PNPGA production by the perfused liver by a factor of 1.7, and biliary excretion of PNPGA by a factor of 1.5. The latter increase was attributed to the increased rate of synthesis of the glucuronide rather than to an increase in the biliary transport maximum, since the 3MC treatment produced no significant effect on the biliary excretion of performed PNPGA added to the perfusate. The 3MC pretreatment increased 1.5-fold the rate of sulfation of PNP, as judged by the increase in R2.", "contents": "Effect of 3-methylcholanthrene pretreatment on glucuronidation and sulfation in perfused rat liver. The metabolism of p-nitro[14C]phenol (PNP) was studied in perfused rat liver. Metabolites were identified in perfusate and bile. The perfusion system containing 0.5 mM PNP, at the start, converted the phenol within 2 hr to p-nitrophenyl glucuronide (PNPGA), 31.4% in perfusate and 21% in bile; p-nitrophenyl sulfate (PNPS), 22% in perfusate; and p-nitrophenyl glucoside (PNPG), between 2 and 4% perfusate. Biliary excretion of PNPS and PNPG accounted for less than 2% of PNP. An apparent maximal rate of PNPGA synthesis by the perfused liver, estimated from the rates of appearance of PNPGA in perfusate and bile, corresponded well to the glucuronyl-transferase activities determined in \"native\" liver homogenates. Sulfation of PNP in the perfused liver exhibited two apparent maximal rates of synthesis, as determined from the rates of appearance of metabolite in the perfusate. A slower rate (R1) occurred when PNP concentration was between 0.13 and 0.5 mM, and a faster rate (R2) when PNP was approximately between 0.025 and 0.13 mM in the perfusate. Possible significance of these findings is discussed. Pretreatment of rats with 3-methylcholanthrene (3MC) increased the apparent maximal rate of PNPGA production by the perfused liver by a factor of 1.7, and biliary excretion of PNPGA by a factor of 1.5. The latter increase was attributed to the increased rate of synthesis of the glucuronide rather than to an increase in the biliary transport maximum, since the 3MC treatment produced no significant effect on the biliary excretion of performed PNPGA added to the perfusate. The 3MC pretreatment increased 1.5-fold the rate of sulfation of PNP, as judged by the increase in R2."}
{"id": "PMID:241626", "title": "Effect of beta and beta2 adrenoreceptor stimulants infused intrapancreatically on glucagon and insulin secretion.", "content": "L-Isoproterenol was infused at a dose of 20 pmol/kg/min for 10 min into the cranial pancreaticoduodenal artery in anesthetized dogs. Arterial plasma glucose, blood flow, and plasma concentrations of both glucagon and insulin in the cranial pancreaticoduodenal vein were significantly enhanced during the infusion, resulting in a greater increase of bihormonal output. Intrapancreatic pretreatment with propranolol abolished all of the isoproterenol-induced increases except for glucagon secretion which was suppressed only in part. Pretreatment with practolol, a specific receptor blocker of the beta1 type, did not exert any discernible inhibiting effect upon the isoproterenol-induced enhancement. Intrapancreatic infusion of trimetoquinol, a selective receptor stimulant of the beta2 type in some mammals, at an equimolar dose caused similar increases in plasma glucose, pancreatic venous blood flow, and bihormonal output when compared to those induced by isoproterenol. Pretreatment with a larger dose of propranolol totally abolished the trimetoquinol-induced enhancement of both glucagon and insulin secretion. Pretreatment with an isomolar dose of practolol, in contrast, did not show any suppressive effect on the parameters investigated. There was a dose-dependency in the bihormonal responses to trimetoquinol. Another beta2 receptor agonist, salbutamol, also significantly raised plasma glucose, pancreatic venous blood flothough to a lesser extent than did trimetoquinol. These results indicate that the adrenergic control over the function of the endocrine pancreas through beta adrenoreceptors may be mediated mainly via those of the beta2 type.", "contents": "Effect of beta and beta2 adrenoreceptor stimulants infused intrapancreatically on glucagon and insulin secretion. L-Isoproterenol was infused at a dose of 20 pmol/kg/min for 10 min into the cranial pancreaticoduodenal artery in anesthetized dogs. Arterial plasma glucose, blood flow, and plasma concentrations of both glucagon and insulin in the cranial pancreaticoduodenal vein were significantly enhanced during the infusion, resulting in a greater increase of bihormonal output. Intrapancreatic pretreatment with propranolol abolished all of the isoproterenol-induced increases except for glucagon secretion which was suppressed only in part. Pretreatment with practolol, a specific receptor blocker of the beta1 type, did not exert any discernible inhibiting effect upon the isoproterenol-induced enhancement. Intrapancreatic infusion of trimetoquinol, a selective receptor stimulant of the beta2 type in some mammals, at an equimolar dose caused similar increases in plasma glucose, pancreatic venous blood flow, and bihormonal output when compared to those induced by isoproterenol. Pretreatment with a larger dose of propranolol totally abolished the trimetoquinol-induced enhancement of both glucagon and insulin secretion. Pretreatment with an isomolar dose of practolol, in contrast, did not show any suppressive effect on the parameters investigated. There was a dose-dependency in the bihormonal responses to trimetoquinol. Another beta2 receptor agonist, salbutamol, also significantly raised plasma glucose, pancreatic venous blood flothough to a lesser extent than did trimetoquinol. These results indicate that the adrenergic control over the function of the endocrine pancreas through beta adrenoreceptors may be mediated mainly via those of the beta2 type."}
{"id": "PMID:241627", "title": "Sex hormones and tyrosine hydroxylase activity in vascular and adrenal tissue.", "content": "Vascular tyrosine hydroxylase (TH) activity did not appear to be affected by the sex hormones. There were no differences in enzyme activity in the mesenteric artery or vein taken from male and female normotensive or spontaneously hypertensive rats. Castration of either male or female rats did not alter mesenteric artery or vein TH activity, and the administration of estradiol, progesterone, or testosterone also had no effect on vascular TH activity. However, the sex hormones did alter activity in other tissues. Estradiol and progesterone administration to intact female rats increased adrenal TH activity, whereas castration of the male rat decreased it. Although the sex hormones were not important regulators of TH in blood vessels, vascular TH activity did appear to be under some hormonal regulation since hypophysectomy decreased mesenteric artery enzyme activity. Hypophysectomy studies also indicated that adrenal TH activity was under some hormonal regulation.", "contents": "Sex hormones and tyrosine hydroxylase activity in vascular and adrenal tissue. Vascular tyrosine hydroxylase (TH) activity did not appear to be affected by the sex hormones. There were no differences in enzyme activity in the mesenteric artery or vein taken from male and female normotensive or spontaneously hypertensive rats. Castration of either male or female rats did not alter mesenteric artery or vein TH activity, and the administration of estradiol, progesterone, or testosterone also had no effect on vascular TH activity. However, the sex hormones did alter activity in other tissues. Estradiol and progesterone administration to intact female rats increased adrenal TH activity, whereas castration of the male rat decreased it. Although the sex hormones were not important regulators of TH in blood vessels, vascular TH activity did appear to be under some hormonal regulation since hypophysectomy decreased mesenteric artery enzyme activity. Hypophysectomy studies also indicated that adrenal TH activity was under some hormonal regulation."}
{"id": "PMID:241628", "title": "Aerobic photodegradation of X(N) chelates of (ethylenedinitrilo)tetraacetic acid (EDTA): implications for natural waters.", "content": "The behavior of several metal chelates [X(N)] of 1-14C-(ethylenedinitrilo) tetraacetic acid [EDTA] under irradiation from a wide spectrum Xenon arc lamp has been studied. In static tests at pH 4.5, chelates of Mn(II), Fe(II) and Co(II) photodegraded to give 14CO2 and CH2O. Chelates of Na(I), Mg(II), Ca(II), Ni(II), Cu(II), Zn(II), Cd(II), and Hg(II) did not exhibit any significant photodegradation as measured by 14CO2 evolution. It is concluded that the photodegradation of Fe(III)-EDTA by sunlight will prevent EDTA build up in natural waters.", "contents": "Aerobic photodegradation of X(N) chelates of (ethylenedinitrilo)tetraacetic acid (EDTA): implications for natural waters. The behavior of several metal chelates [X(N)] of 1-14C-(ethylenedinitrilo) tetraacetic acid [EDTA] under irradiation from a wide spectrum Xenon arc lamp has been studied. In static tests at pH 4.5, chelates of Mn(II), Fe(II) and Co(II) photodegraded to give 14CO2 and CH2O. Chelates of Na(I), Mg(II), Ca(II), Ni(II), Cu(II), Zn(II), Cd(II), and Hg(II) did not exhibit any significant photodegradation as measured by 14CO2 evolution. It is concluded that the photodegradation of Fe(III)-EDTA by sunlight will prevent EDTA build up in natural waters."}
{"id": "PMID:241629", "title": "Adsorpition of tryptophan onto calcum carbonate surface.", "content": "Adsorption of tryptophan onto CaCO3 at constant ionic strength (0.05 M Nacl) and from dilute aqueous solution (10(-4) M to 10(-3) M tryptophan) is reported. Adsorption was primarily determined by the charge characteristics of both the adsorbate amino acid and adsorbent CaCO3. When both adsorbate and adsorbent are semicharged, tryptophan ions are expelled away from the CaCO3-solution interface. Tryptophan is only removed by CaCO3 in a narrow pH range, 6.0 greater than pH less than 8.5 within which CaCO3 has positive charges, and tryptophan is negatively charged. The pH of zero point of charge, pHzpc, of CaCO3 was also determined by alkalimetric tritration and coagulation techniques and a value of 9.50 +/- 0.5 was found. These preliminary finding demonstrate primarily that interfacial chemical reactions play an important role in the temporal and spatial transformation of dissolved organic matter in natural water systems.", "contents": "Adsorpition of tryptophan onto calcum carbonate surface. Adsorption of tryptophan onto CaCO3 at constant ionic strength (0.05 M Nacl) and from dilute aqueous solution (10(-4) M to 10(-3) M tryptophan) is reported. Adsorption was primarily determined by the charge characteristics of both the adsorbate amino acid and adsorbent CaCO3. When both adsorbate and adsorbent are semicharged, tryptophan ions are expelled away from the CaCO3-solution interface. Tryptophan is only removed by CaCO3 in a narrow pH range, 6.0 greater than pH less than 8.5 within which CaCO3 has positive charges, and tryptophan is negatively charged. The pH of zero point of charge, pHzpc, of CaCO3 was also determined by alkalimetric tritration and coagulation techniques and a value of 9.50 +/- 0.5 was found. These preliminary finding demonstrate primarily that interfacial chemical reactions play an important role in the temporal and spatial transformation of dissolved organic matter in natural water systems."}
{"id": "PMID:241630", "title": "Ion-binding to phospholipids. Interaction of calcium and lanthanide ions with phosphatidylcholine (lecithin).", "content": "Surface chemical and nuclear magnetic resonance (NMR) techniques have been used to study the interaction of Ca2+ and lanthanides with lecithins. With both methods positive reactions were detected at metal concentrations greater than 0.1 mM. 1H and 31P high-resolution NMR spectra obtained with single bilayer vesicles of lecithin were invariant up to Ca2+ concentrations of 0.1 M indicating that there is only a loose association between Ca2+ and the phospholipid. The weak interaction between Ca2+ and lecithin is confirmed by both surface chemical and NMR techniques showing that the packing of egg lecithin molecules present in bilayers does not change up to Ca2+ concentrations of about 0.1 M. The packing was also independent of pH between 1--10. Contradictory results have been reported in the literature concerning the question of Ca2+ binding to lecithins. The conflicting results are shown to have arisen from differences in the experimental conditions and differences in the sensitivity of the physical methods used by various authors to study Ca2+ -lecithin interactions. An estimate of the strength of binding and molecular details of the interaction were derived using paramagnetic lanthanides as isomorphous replacements for Ca2+. From the changes in chemical shifts induced in the presence of lanthanides an apparent binding constant KA approximately 30 l/mol was calculated at lanthanide concentrations greater than 10 mM. Using surface chemical methods it was shown that this KA is up to 10 times larger than that for Ca2+ binding. The complete assignment of the 1H NMR spectrum of lecithin, including the resonances from the relatively immobilized glycerol group, was determined to derive molecular details of the cation-lecithin interaction. From spin-lattice relaxation-time measurements and line broadening in the presence of GdCl3 it is concluded that the cations are bound to the phosphate group and that this is the only binding site. The absolute proton shifts induced by paramagnetic lanthanides depended on the nature of the ion, but the shift ratios standardised to the shift of the O3POCH2 (choline) signal were invariant throughout the lanthanide series indicating that the shifts are purely pseudocontact. In contrast the 31P shifts were found to contain significant contact contributions. These findings are consistent with a weak interaction and with the phosphate group being the binding site. The absolute shifts but not the shift ratios depended on the anion present indicating that the cation binding may be accompanied by binding of anions. Contrary to negatively charged phospholipids the interaction of lanthanides with lecithins was enhanced as the ionic strength was increased by adding NaCl. This was explained in terms of steric hindrance due to the extended conformation of the lecithin polar group.", "contents": "Ion-binding to phospholipids. Interaction of calcium and lanthanide ions with phosphatidylcholine (lecithin). Surface chemical and nuclear magnetic resonance (NMR) techniques have been used to study the interaction of Ca2+ and lanthanides with lecithins. With both methods positive reactions were detected at metal concentrations greater than 0.1 mM. 1H and 31P high-resolution NMR spectra obtained with single bilayer vesicles of lecithin were invariant up to Ca2+ concentrations of 0.1 M indicating that there is only a loose association between Ca2+ and the phospholipid. The weak interaction between Ca2+ and lecithin is confirmed by both surface chemical and NMR techniques showing that the packing of egg lecithin molecules present in bilayers does not change up to Ca2+ concentrations of about 0.1 M. The packing was also independent of pH between 1--10. Contradictory results have been reported in the literature concerning the question of Ca2+ binding to lecithins. The conflicting results are shown to have arisen from differences in the experimental conditions and differences in the sensitivity of the physical methods used by various authors to study Ca2+ -lecithin interactions. An estimate of the strength of binding and molecular details of the interaction were derived using paramagnetic lanthanides as isomorphous replacements for Ca2+. From the changes in chemical shifts induced in the presence of lanthanides an apparent binding constant KA approximately 30 l/mol was calculated at lanthanide concentrations greater than 10 mM. Using surface chemical methods it was shown that this KA is up to 10 times larger than that for Ca2+ binding. The complete assignment of the 1H NMR spectrum of lecithin, including the resonances from the relatively immobilized glycerol group, was determined to derive molecular details of the cation-lecithin interaction. From spin-lattice relaxation-time measurements and line broadening in the presence of GdCl3 it is concluded that the cations are bound to the phosphate group and that this is the only binding site. The absolute proton shifts induced by paramagnetic lanthanides depended on the nature of the ion, but the shift ratios standardised to the shift of the O3POCH2 (choline) signal were invariant throughout the lanthanide series indicating that the shifts are purely pseudocontact. In contrast the 31P shifts were found to contain significant contact contributions. These findings are consistent with a weak interaction and with the phosphate group being the binding site. The absolute shifts but not the shift ratios depended on the anion present indicating that the cation binding may be accompanied by binding of anions. Contrary to negatively charged phospholipids the interaction of lanthanides with lecithins was enhanced as the ionic strength was increased by adding NaCl. This was explained in terms of steric hindrance due to the extended conformation of the lecithin polar group."}
{"id": "PMID:241631", "title": "Highly purified glutamine transaminase from rat brain. Physical and kinetic properties.", "content": "Glutamine transaminase from rat brain was purified to a high degree. The isolated enzyme appeared to be homogeneous by electrophoresis on polyacrylamide gel. The molecular weight was found to be approximately 98 000; the enzyme is probably composed of two subunits. The absorbance maximum at 410 nm and the inhibition by carbonyl reagents are strong indications for the presence of pyridoxal phosphate. The enzyme showed maximal activity at pH 9.0 to 9.2. Of the amino acids tested, none could replace glutamine in the transamination reaction. Glyoxylate and phenylpyruvate was found to be the best amino acceptors. The Km values for glutamine and glyoxylate were 0.6 and 1.5 mM, respectively.", "contents": "Highly purified glutamine transaminase from rat brain. Physical and kinetic properties. Glutamine transaminase from rat brain was purified to a high degree. The isolated enzyme appeared to be homogeneous by electrophoresis on polyacrylamide gel. The molecular weight was found to be approximately 98 000; the enzyme is probably composed of two subunits. The absorbance maximum at 410 nm and the inhibition by carbonyl reagents are strong indications for the presence of pyridoxal phosphate. The enzyme showed maximal activity at pH 9.0 to 9.2. Of the amino acids tested, none could replace glutamine in the transamination reaction. Glyoxylate and phenylpyruvate was found to be the best amino acceptors. The Km values for glutamine and glyoxylate were 0.6 and 1.5 mM, respectively."}
{"id": "PMID:241632", "title": "Influence of various factors on the recognition specificity of tRNAs by yeast valyl-tRNA synthetase.", "content": "Using filtration through nitrocellulose membranes we found that complexes between yeast valyl-tRNA synthetase can easily be detected at low pH and ionic strength with the cognate tRNAVal, but also with several non-cognate tRNAs (tRNAPhe, tRNATyr, tRNAMet and tRNAAsp). We show here that the amino acid linked to the tRNA has no detectable effect on these interactions. The influence of various factors on the discrimination by the enzyme between the cognate and the non-cognate tRNAs has been studied. An increase in pH or ionic strength leads to a decrease in the same ratio of the affinity constants between the enzyme and the cognate as well as the noncognate tRNA. The addition of organic solvents has little effect on these constant either in the cognate or in the non-cognate systems; the addition of substrates of the aminoacylation reaction has not effect on the ratio between the constants. This similar behaviour suggests that at least part of the specific of non-specific interactions must be identical. On the contrary, magnesium between 1 mM and 50 mM increases the specificity of recognition, showing the importance of slight conformational changes in the tRNA molecule to the specificity of interaction.", "contents": "Influence of various factors on the recognition specificity of tRNAs by yeast valyl-tRNA synthetase. Using filtration through nitrocellulose membranes we found that complexes between yeast valyl-tRNA synthetase can easily be detected at low pH and ionic strength with the cognate tRNAVal, but also with several non-cognate tRNAs (tRNAPhe, tRNATyr, tRNAMet and tRNAAsp). We show here that the amino acid linked to the tRNA has no detectable effect on these interactions. The influence of various factors on the discrimination by the enzyme between the cognate and the non-cognate tRNAs has been studied. An increase in pH or ionic strength leads to a decrease in the same ratio of the affinity constants between the enzyme and the cognate as well as the noncognate tRNA. The addition of organic solvents has little effect on these constant either in the cognate or in the non-cognate systems; the addition of substrates of the aminoacylation reaction has not effect on the ratio between the constants. This similar behaviour suggests that at least part of the specific of non-specific interactions must be identical. On the contrary, magnesium between 1 mM and 50 mM increases the specificity of recognition, showing the importance of slight conformational changes in the tRNA molecule to the specificity of interaction."}
{"id": "PMID:241633", "title": "A fluorescence study of the temperature-dependent polymerization of bovine beta-casein A1.", "content": "The intrinsic fluorescence properties of bovine beta-casein A1 solutions have been studied under a variety of conditions. The protein shows both tyrosine and tryptophan fluorescence emission, the former being more pronounced at low temperature (5 degrees C) and in the presence of urea. Approximate relative quantum yields for the tyrosine and tryptophan residues were determined using free tyrosine and free tryptophan respectively as standards. The tryptophan emission intensity of beta-casein shows an increase with temperature indicating a temperature-dependent transition of the protein. Two-state analysis of the emission-intensity--temperature data yielded positive enthalpy and entropy values for the transition over a range of protein concentrations (0.018--0.18%). A marked protein concentration effect was apparent which indicated that the transition was a consequence of polymerization rather than a prerequisite for polymerization. The size of the polymers appeared to be concentration-dependent. Decreased ionic strength and increased pH both caused a reduction in the increase in emission intensity when the temperature was increased. At higher pH both the enthalpy and the entropy for the transition were reduced. Experimental precision was insufficient to allow the effect of decreased ionic strength on these parameters to be determined. Many of the properties of the temperature-dependent transition can be explained if the transition is considered to be one of micelle formation.", "contents": "A fluorescence study of the temperature-dependent polymerization of bovine beta-casein A1. The intrinsic fluorescence properties of bovine beta-casein A1 solutions have been studied under a variety of conditions. The protein shows both tyrosine and tryptophan fluorescence emission, the former being more pronounced at low temperature (5 degrees C) and in the presence of urea. Approximate relative quantum yields for the tyrosine and tryptophan residues were determined using free tyrosine and free tryptophan respectively as standards. The tryptophan emission intensity of beta-casein shows an increase with temperature indicating a temperature-dependent transition of the protein. Two-state analysis of the emission-intensity--temperature data yielded positive enthalpy and entropy values for the transition over a range of protein concentrations (0.018--0.18%). A marked protein concentration effect was apparent which indicated that the transition was a consequence of polymerization rather than a prerequisite for polymerization. The size of the polymers appeared to be concentration-dependent. Decreased ionic strength and increased pH both caused a reduction in the increase in emission intensity when the temperature was increased. At higher pH both the enthalpy and the entropy for the transition were reduced. Experimental precision was insufficient to allow the effect of decreased ionic strength on these parameters to be determined. Many of the properties of the temperature-dependent transition can be explained if the transition is considered to be one of micelle formation."}
{"id": "PMID:241634", "title": "The location and function of cytochrome c2 in Rhodopseudomonas capsulate membranes.", "content": "Two fractions of membrane preparations, a heavy and a light one were isolated from mildly broken Rhodopseudomonas capsulata cells. The light fraction which contained vesicles similar to the regular chromatophores obtained by sonication and a heavy fraction which appeared in electron micrographs to consist of cell fragments which were designated as heavy chromatophores and were composed of broken cell envelopes containing closely packed vesicles enclosed within the cytoplasmic membrane. Both types of chromatophores catalyzed photophosphorylation. However, cytochrome c2 could be washed out only from the heavy chromatophores. Photophosphorylation activity which was lost by the removal of the cytochrome could be restored by addition of either cytochrome c2 or phenazine methosulphate. Light induced proton efflux in heavy chromatophores in contrast to proton influx in regular chromatophores. The washed heavy chromatophores did not lose the light induced proton movement. Light induced quenching of 9-aminoacridine and atebrin fluorescence in chromatophores, while the fluorescence was enhanced in the heavy chromatophores. The washing did not affect the fluorescence changes of the heavy chromatophores but caused a reduction of the steady state of the carotenoid absorbance shift. It is suggested that the membrane in the heavy chromatophores is oriented inside out with respect to the membrane in regular chromatophores. Cytochrome c2 which is attached to that side of the membrane facing the outside medium could be removed from the heavy chromatophors and reconstituted to them. The role of cytochrome c2 in photophosphorylation is discussed.", "contents": "The location and function of cytochrome c2 in Rhodopseudomonas capsulate membranes. Two fractions of membrane preparations, a heavy and a light one were isolated from mildly broken Rhodopseudomonas capsulata cells. The light fraction which contained vesicles similar to the regular chromatophores obtained by sonication and a heavy fraction which appeared in electron micrographs to consist of cell fragments which were designated as heavy chromatophores and were composed of broken cell envelopes containing closely packed vesicles enclosed within the cytoplasmic membrane. Both types of chromatophores catalyzed photophosphorylation. However, cytochrome c2 could be washed out only from the heavy chromatophores. Photophosphorylation activity which was lost by the removal of the cytochrome could be restored by addition of either cytochrome c2 or phenazine methosulphate. Light induced proton efflux in heavy chromatophores in contrast to proton influx in regular chromatophores. The washed heavy chromatophores did not lose the light induced proton movement. Light induced quenching of 9-aminoacridine and atebrin fluorescence in chromatophores, while the fluorescence was enhanced in the heavy chromatophores. The washing did not affect the fluorescence changes of the heavy chromatophores but caused a reduction of the steady state of the carotenoid absorbance shift. It is suggested that the membrane in the heavy chromatophores is oriented inside out with respect to the membrane in regular chromatophores. Cytochrome c2 which is attached to that side of the membrane facing the outside medium could be removed from the heavy chromatophors and reconstituted to them. The role of cytochrome c2 in photophosphorylation is discussed."}
{"id": "PMID:241635", "title": "Structure and synthesis of a lipid-containing bacteriophage. A polynucleotide-dependent polynucleotide-pyrophosphorylase activity in bacteriophage PM2.", "content": "A polymerase activity is associated with protein IV, a protein which is associated with the DNA in bacteriophage PM2. The native enzyme unit is probably a dimer. Manganese ions are required for the polymerisation reaction and there is a well-defined Mn2+ optimum at 2.5 mM. The pH optimum is at 8.1, the temperature optimum at 28 degrees C. The activity is a polynucleotide-pyrophosphorylating reaction in the presence of ribo- or deoxyribonucleoside triphosphates. The polymerisation reaction is stimulated in the presence of nuclei- acids or polynucleotides as effectors. The product is not covalently linked to the effector.", "contents": "Structure and synthesis of a lipid-containing bacteriophage. A polynucleotide-dependent polynucleotide-pyrophosphorylase activity in bacteriophage PM2. A polymerase activity is associated with protein IV, a protein which is associated with the DNA in bacteriophage PM2. The native enzyme unit is probably a dimer. Manganese ions are required for the polymerisation reaction and there is a well-defined Mn2+ optimum at 2.5 mM. The pH optimum is at 8.1, the temperature optimum at 28 degrees C. The activity is a polynucleotide-pyrophosphorylating reaction in the presence of ribo- or deoxyribonucleoside triphosphates. The polymerisation reaction is stimulated in the presence of nuclei- acids or polynucleotides as effectors. The product is not covalently linked to the effector."}
{"id": "PMID:241636", "title": "Lysosomal enzymes as agents of turnover of soluble cytoplasmic proteins.", "content": "The degradation of cytosol proteins in vitro by purified cathepsin D and cathepsin B1 and by mixtures of lysosomal enzymes, was studied. By means of a double-labelling method, it was shown  that the relative rates of degradation of cytosol proteins by the purified enzymes and by mixtures of enzymes under a wide range of conditions in vitro correlated well with their relative rates of turnover in vivo. The complex mixture of cytosol proteins was degraded less rapidly after denaturation than in the native state, both by the purified proteases and by the mixture of lysosomal enzymes. This contrasts with previous results on proteolysis of single purified proteins. The possible role of lysosomal enzymes in turnover in vivo was discussed.", "contents": "Lysosomal enzymes as agents of turnover of soluble cytoplasmic proteins. The degradation of cytosol proteins in vitro by purified cathepsin D and cathepsin B1 and by mixtures of lysosomal enzymes, was studied. By means of a double-labelling method, it was shown  that the relative rates of degradation of cytosol proteins by the purified enzymes and by mixtures of enzymes under a wide range of conditions in vitro correlated well with their relative rates of turnover in vivo. The complex mixture of cytosol proteins was degraded less rapidly after denaturation than in the native state, both by the purified proteases and by the mixture of lysosomal enzymes. This contrasts with previous results on proteolysis of single purified proteins. The possible role of lysosomal enzymes in turnover in vivo was discussed."}
{"id": "PMID:241637", "title": "Fractionation of rat-liver-chromatin nonhistone proteins into two groups with different metabolic rates.", "content": "In the pH interval 10.5-11.8, 70% of the nonhistone proteins normally present in rat liver chromatin were dissociated. The rest remained complexed with DNA even at pH 13. Dodecylsulfate-polyacrylamide gel electrophoresis revealed that the majority of the high-molecular-weight nonhistone proteins together with a few characteristic fractions with molecular weights of 40 000-60 000 remained in the alkali-resistant group. L-[14C]Leucine pulse-labelling experiments showed that the specific radioactivity of the alkali-labile nonhistone proteins was 2-3 times higher than that of the alkali-resistant nonhistone proteins, which, in turn, had the same specific radioactivity as that of the histones. The same held true for chromatin from regenerating rat liver. In the course of a 21-day chase the specific radioactivity of the alkali-labile nonhistone proteins gradually decreased and finally became 3 times lower than that of the alkali-resistant nonhistone proteins. On the contrary, the ratio of the specific radioactivities of the alkali-resistant nonhistone proteins and of the histones to the specific radioactivity of DNA remained constant during the chase. A conclusion can be drawn that a fraction of liver nonhistone proteins exists which is alkali-resistant and is conserved in chromatin like histones.", "contents": "Fractionation of rat-liver-chromatin nonhistone proteins into two groups with different metabolic rates. In the pH interval 10.5-11.8, 70% of the nonhistone proteins normally present in rat liver chromatin were dissociated. The rest remained complexed with DNA even at pH 13. Dodecylsulfate-polyacrylamide gel electrophoresis revealed that the majority of the high-molecular-weight nonhistone proteins together with a few characteristic fractions with molecular weights of 40 000-60 000 remained in the alkali-resistant group. L-[14C]Leucine pulse-labelling experiments showed that the specific radioactivity of the alkali-labile nonhistone proteins was 2-3 times higher than that of the alkali-resistant nonhistone proteins, which, in turn, had the same specific radioactivity as that of the histones. The same held true for chromatin from regenerating rat liver. In the course of a 21-day chase the specific radioactivity of the alkali-labile nonhistone proteins gradually decreased and finally became 3 times lower than that of the alkali-resistant nonhistone proteins. On the contrary, the ratio of the specific radioactivities of the alkali-resistant nonhistone proteins and of the histones to the specific radioactivity of DNA remained constant during the chase. A conclusion can be drawn that a fraction of liver nonhistone proteins exists which is alkali-resistant and is conserved in chromatin like histones."}
{"id": "PMID:241638", "title": "Polynucleotide kinase from rat-liver nuclei. Purification and properties.", "content": "A polynucleotide kinase, which catalyzes the phosphorylation of 5'-hydroxyl ends of deoxyribonucleic acid in the presence of adenosine triphosphate, has been purified 260-fold with a yield of 14% from 0.15 M NaCl extracts of rat liver nuclei. The purified enzyme has a pH optimum of 5.5. The enzyme is reversible inhibited by p-chloromercuribenzoate. The S0.5 value (ligand concentration required for a half-maximal activity) for ATP is 2.5 muM. A bivalent cation is essential for the reaction and S0.5 values for Mg2+, Ca2+ and Mn2+ are 3.3 mM, 4 mM and 0.05 mM respectively. Pyrophosphate remarkable inhibits the activity with I0.5 value (ligand concentration required for a half-maximal inhibition) of 0.2 mM, and sulfate, with I0.5 of 0.5 mM, whereas phosphate weakly inhibits the activity with I0.5 of about 20 mM. An apparent molecular weight of the purified enzyme is estimated to be 8 X 10(4) by gel filtration on a column of Sephadex G-150, and the Stokes radius of the enzyme molecule is shown to be about 0.36 nm. Sucrose density gradient centrifugation reveals that the enzyme has a sedimentation coefficient of about 4.4 S.", "contents": "Polynucleotide kinase from rat-liver nuclei. Purification and properties. A polynucleotide kinase, which catalyzes the phosphorylation of 5'-hydroxyl ends of deoxyribonucleic acid in the presence of adenosine triphosphate, has been purified 260-fold with a yield of 14% from 0.15 M NaCl extracts of rat liver nuclei. The purified enzyme has a pH optimum of 5.5. The enzyme is reversible inhibited by p-chloromercuribenzoate. The S0.5 value (ligand concentration required for a half-maximal activity) for ATP is 2.5 muM. A bivalent cation is essential for the reaction and S0.5 values for Mg2+, Ca2+ and Mn2+ are 3.3 mM, 4 mM and 0.05 mM respectively. Pyrophosphate remarkable inhibits the activity with I0.5 value (ligand concentration required for a half-maximal inhibition) of 0.2 mM, and sulfate, with I0.5 of 0.5 mM, whereas phosphate weakly inhibits the activity with I0.5 of about 20 mM. An apparent molecular weight of the purified enzyme is estimated to be 8 X 10(4) by gel filtration on a column of Sephadex G-150, and the Stokes radius of the enzyme molecule is shown to be about 0.36 nm. Sucrose density gradient centrifugation reveals that the enzyme has a sedimentation coefficient of about 4.4 S."}
{"id": "PMID:241639", "title": "The photochemical inactivation of peptidyl transferase activity.", "content": "The photochemical oxidation of the 50-S ribosomal subunit results in a rapid irreversible loss of peptidyl transferase activity. The first-order rate of inactivation occurring during the first forty minutes suggests that a single reactive group is being inactivation exhibits a maximum at pH 7.5. Erythromycin at a low concentration (0.04 mumol) affords significant protection. Puromycin also exerts a protective effect but at higher concentrations. Chloramphenicol, sparsomycin and lincomycin did not exert a protective effect. The loss in catalytic activity was not accompanied by a loss in substrate binding affinity of the donor and acceptor substrates.", "contents": "The photochemical inactivation of peptidyl transferase activity. The photochemical oxidation of the 50-S ribosomal subunit results in a rapid irreversible loss of peptidyl transferase activity. The first-order rate of inactivation occurring during the first forty minutes suggests that a single reactive group is being inactivation exhibits a maximum at pH 7.5. Erythromycin at a low concentration (0.04 mumol) affords significant protection. Puromycin also exerts a protective effect but at higher concentrations. Chloramphenicol, sparsomycin and lincomycin did not exert a protective effect. The loss in catalytic activity was not accompanied by a loss in substrate binding affinity of the donor and acceptor substrates."}
{"id": "PMID:241640", "title": "Properties of the high-molecular-weight protein (spectrin) from human-erythrocyte membranes.", "content": "The high-molecular-weight protein component from human erythrocytes has been isolated and its solubility properties studied. In physiological solvent conditions the spectrin is not aggregated and is unaffected, both in hydrodynamic properties and conformation, as judged by circular dichroism and intrinsic fluorescence, by the addition of calcium ions. When the pH is decreased an opalescence first sets in, which corresponds to an associated fibrous state of the protein, and when a critical pH is reached precipitation ensues. The precipitation profile is characterised by extreme sharpness, of the kind observed in the phase separation of polyacid-polybase mixtures or of polyampholytes. The addition of calcium ions displaces this precipitation edge towards higher pH. Sodium ions have a similar but smaller effect. The position of the profile is significantly displaced in aged spectrin preparations, or those from frozen erythrocyte ghosts. Fresh preparations of spectrin consist predominantly of a component sedimenting at 9.7 S, with a minor component at 4.4 S (and traces of higher aggregates). The pattern is independent of the ionic strength, or of the presence or absence of calcium ions. The proportion of the small component increases with time, and in spectrin preparations from frozen ghosts it invariably predominates. At low concentrations of guanidine hydrochloride the larger component gives place progressively to the smaller, and vanishes completely when the concentration of the denaturant reaches 1 M. The two components coexist at concentrations below this, and are not in rapid interconversion equilibrium. On recovery of the protein from the guanidine hydrochloride by dialysis, the original pattern of two components is regained. On the other hand the larger component is not found in the material recovered from guanidine hydrochloride solutions of preparations that contain only the small component at the outset. The recovered spectrin is similar to the starting material in its circular dichroism, in its pH-precipitation profiles, and the manner in which the latter is modified by calcium ions. Molecular weight determination by sedimentation equilibrium shows that the 4.4-S species has a molecular weight of some 230 000, which is also the value derived from the extrapolated sedimentation coeffiecient in 6 M guanidine hydrochloride, and thus corresponds to single chains (of which two or more species are resolved in acrylamide gel electrophoresis in the presence of sodium dodecylsulphate); the 9.7-S species, which characterises what is evidently the native state of the extracted spectrin, is found to be a dimer. The frictional coefficients of the monomer and dimer are appreciably different. That of the dimer is compatible with a somewhat asymmetric structure, but by no means to the extent expected for a myosin-like or paramyosin-like molecule.", "contents": "Properties of the high-molecular-weight protein (spectrin) from human-erythrocyte membranes. The high-molecular-weight protein component from human erythrocytes has been isolated and its solubility properties studied. In physiological solvent conditions the spectrin is not aggregated and is unaffected, both in hydrodynamic properties and conformation, as judged by circular dichroism and intrinsic fluorescence, by the addition of calcium ions. When the pH is decreased an opalescence first sets in, which corresponds to an associated fibrous state of the protein, and when a critical pH is reached precipitation ensues. The precipitation profile is characterised by extreme sharpness, of the kind observed in the phase separation of polyacid-polybase mixtures or of polyampholytes. The addition of calcium ions displaces this precipitation edge towards higher pH. Sodium ions have a similar but smaller effect. The position of the profile is significantly displaced in aged spectrin preparations, or those from frozen erythrocyte ghosts. Fresh preparations of spectrin consist predominantly of a component sedimenting at 9.7 S, with a minor component at 4.4 S (and traces of higher aggregates). The pattern is independent of the ionic strength, or of the presence or absence of calcium ions. The proportion of the small component increases with time, and in spectrin preparations from frozen ghosts it invariably predominates. At low concentrations of guanidine hydrochloride the larger component gives place progressively to the smaller, and vanishes completely when the concentration of the denaturant reaches 1 M. The two components coexist at concentrations below this, and are not in rapid interconversion equilibrium. On recovery of the protein from the guanidine hydrochloride by dialysis, the original pattern of two components is regained. On the other hand the larger component is not found in the material recovered from guanidine hydrochloride solutions of preparations that contain only the small component at the outset. The recovered spectrin is similar to the starting material in its circular dichroism, in its pH-precipitation profiles, and the manner in which the latter is modified by calcium ions. Molecular weight determination by sedimentation equilibrium shows that the 4.4-S species has a molecular weight of some 230 000, which is also the value derived from the extrapolated sedimentation coeffiecient in 6 M guanidine hydrochloride, and thus corresponds to single chains (of which two or more species are resolved in acrylamide gel electrophoresis in the presence of sodium dodecylsulphate); the 9.7-S species, which characterises what is evidently the native state of the extracted spectrin, is found to be a dimer. The frictional coefficients of the monomer and dimer are appreciably different. That of the dimer is compatible with a somewhat asymmetric structure, but by no means to the extent expected for a myosin-like or paramyosin-like molecule."}
{"id": "PMID:241641", "title": "Control of haemoglobin synthesis. The effects of iron deprivation, cobalt and temperature on the rate and extent of globin synthesis in reticulocytes.", "content": "A detailed examination of the kinetics of protein synthesis in rabbit reticulocytes in the presence of the iron chelating agent 2,2'-dipyridyl showed that between 30 degrees C and 42 degrees C there were characteristically two distinct phases of protein synthesis. An initial phase (I), in which no inhibition of protein synthesis was apparent, was followed by a gradual decline in the rate of protein synthesis leading to the second phase (II) in which protein synthesis occurred at a linear but inhibited rate for extended periods. In contrast, below 30 degrees C, incubation in the presence of dipyridyl caused no inhibition of protein synthesis. Between 30 degrees C and 42 degrees C the duration and amount of protein synthesis occurring in phase I before the onset of inhibition were inversely related of the inhibition as was the final rate of incorporation in phase II. During phase II, a partial reversal of the inhibition caused by dipyridyl was obtained by lowering the incubation temperature. This resulted in a burst of protein synthesis at the uninhibited rate until the amount of protein synthesis reached the same level as that in reticulocytes maintained continuously with dipyridyl at the lower incubation temperature. This burst of synthesis was observed in reticulocytes which had been held in phase II for as long as 90 min. It was also possible to reverse the inhibition by addition of haemin to cells in phase II. At any particular incubation temperature, a fixed number of rounds of protein synthesis had to occur before the onset of phase II became apparent. By the use of puromycin we showed that this was not a requirement for the synthesis of globin or of any other protein. We believe that this critical amount of protein synthesis reflects the residual ability of reticulocytes to initiate new protein chains in the absence of concurrent haem synthesis. Reticulocytes preincubated in the presence of cobaltous ions showed almost no inhibition of protein synthesis upon subsequent incubation with dipyridyl. The results are compared to those obtained in reticulocyte lysates and are discussed in terms of current theories to account for control of protein chain initiation by haemin.", "contents": "Control of haemoglobin synthesis. The effects of iron deprivation, cobalt and temperature on the rate and extent of globin synthesis in reticulocytes. A detailed examination of the kinetics of protein synthesis in rabbit reticulocytes in the presence of the iron chelating agent 2,2'-dipyridyl showed that between 30 degrees C and 42 degrees C there were characteristically two distinct phases of protein synthesis. An initial phase (I), in which no inhibition of protein synthesis was apparent, was followed by a gradual decline in the rate of protein synthesis leading to the second phase (II) in which protein synthesis occurred at a linear but inhibited rate for extended periods. In contrast, below 30 degrees C, incubation in the presence of dipyridyl caused no inhibition of protein synthesis. Between 30 degrees C and 42 degrees C the duration and amount of protein synthesis occurring in phase I before the onset of inhibition were inversely related of the inhibition as was the final rate of incorporation in phase II. During phase II, a partial reversal of the inhibition caused by dipyridyl was obtained by lowering the incubation temperature. This resulted in a burst of protein synthesis at the uninhibited rate until the amount of protein synthesis reached the same level as that in reticulocytes maintained continuously with dipyridyl at the lower incubation temperature. This burst of synthesis was observed in reticulocytes which had been held in phase II for as long as 90 min. It was also possible to reverse the inhibition by addition of haemin to cells in phase II. At any particular incubation temperature, a fixed number of rounds of protein synthesis had to occur before the onset of phase II became apparent. By the use of puromycin we showed that this was not a requirement for the synthesis of globin or of any other protein. We believe that this critical amount of protein synthesis reflects the residual ability of reticulocytes to initiate new protein chains in the absence of concurrent haem synthesis. Reticulocytes preincubated in the presence of cobaltous ions showed almost no inhibition of protein synthesis upon subsequent incubation with dipyridyl. The results are compared to those obtained in reticulocyte lysates and are discussed in terms of current theories to account for control of protein chain initiation by haemin."}
{"id": "PMID:241642", "title": "Co-fractionation of an endonuclease activity during the purification of DNA polymerase-alpha from regenerating rat liver. Properties and separation from DNA polymerase.", "content": "The presence of endonuclease activity associated with DNA polymerase was detected during the purification of high-molecular-weight DNA polymerase-alpha from regenerating rat liver by the use of a highly sensitive test. This endonuclease activity co-fractionated with DNA polymerase in a great variety of purification procedures involving ion-exchange chromatographies or molecular weight fractionation, but was further completely separated from DNA polymerase activity by using affinity chromatography on DNA-cellulose. The endonuclease acted on native or denatured DNA by introducing single-strand nicks in the DNA molecules; its enzymatic properties indicate that it could act in polymerisation conditions in vitro.", "contents": "Co-fractionation of an endonuclease activity during the purification of DNA polymerase-alpha from regenerating rat liver. Properties and separation from DNA polymerase. The presence of endonuclease activity associated with DNA polymerase was detected during the purification of high-molecular-weight DNA polymerase-alpha from regenerating rat liver by the use of a highly sensitive test. This endonuclease activity co-fractionated with DNA polymerase in a great variety of purification procedures involving ion-exchange chromatographies or molecular weight fractionation, but was further completely separated from DNA polymerase activity by using affinity chromatography on DNA-cellulose. The endonuclease acted on native or denatured DNA by introducing single-strand nicks in the DNA molecules; its enzymatic properties indicate that it could act in polymerisation conditions in vitro."}
{"id": "PMID:241643", "title": "Patulin biosynthesis: the metabolism of m-hydroxybenzyl alcohol and m-hydroxybenzaldehyde by particulate preparations from Penicillium patulum.", "content": "The ring hydroxylation of m-hydroxybenzyl alcohol to gentisyl alcohol by a particulate preparation from Penicillium patulum has been characterised. The activity was shown to be closely associated with, but not necessarily identical to, m-cresol 2-hydroxylase activity of the 105 000 X g microsomal fraction. As with both the m-cresol hydroxylases of this system, m-hydroxybenzyl alcohol hydroxylase required oxygen and NADPH for activity. A Km value for m-hydroxybenzyl alcohol of 15 muM was measured. Inhibition of the hydroxylase activity and its reversal by light, as well as the action of cytochrome c, KCN and other effectors suggested a mixed-function oxidase reaction of the cytochrome P-450, NADPH-cytochrome reductase type. m-Hydroxybenzaldehyde was not ring hydroxylated by any preparation from P. patulum. Apart from the previously described conversion to m-hydroxybenzyl alcohol by a predominantly soluble dehydrogenase, m-hydroxybenzaldehyde was metabolized to m-hydroxybenzoic acid by a particulate fraction. This activity required NADPH. It was concluded that the main biosynthetic pathway to patulin must be through m-hydroxybenzyl alcohol, gentisyl alcohol and gentisaldehyde.", "contents": "Patulin biosynthesis: the metabolism of m-hydroxybenzyl alcohol and m-hydroxybenzaldehyde by particulate preparations from Penicillium patulum. The ring hydroxylation of m-hydroxybenzyl alcohol to gentisyl alcohol by a particulate preparation from Penicillium patulum has been characterised. The activity was shown to be closely associated with, but not necessarily identical to, m-cresol 2-hydroxylase activity of the 105 000 X g microsomal fraction. As with both the m-cresol hydroxylases of this system, m-hydroxybenzyl alcohol hydroxylase required oxygen and NADPH for activity. A Km value for m-hydroxybenzyl alcohol of 15 muM was measured. Inhibition of the hydroxylase activity and its reversal by light, as well as the action of cytochrome c, KCN and other effectors suggested a mixed-function oxidase reaction of the cytochrome P-450, NADPH-cytochrome reductase type. m-Hydroxybenzaldehyde was not ring hydroxylated by any preparation from P. patulum. Apart from the previously described conversion to m-hydroxybenzyl alcohol by a predominantly soluble dehydrogenase, m-hydroxybenzaldehyde was metabolized to m-hydroxybenzoic acid by a particulate fraction. This activity required NADPH. It was concluded that the main biosynthetic pathway to patulin must be through m-hydroxybenzyl alcohol, gentisyl alcohol and gentisaldehyde."}
{"id": "PMID:241644", "title": "Formation, size, and solubility in chloroform/methanol of products of protein synthesis in isolated mitochondria of rat liver and Zajdela hepatoma.", "content": "The number, size, solubility in chloroform/methanol and some aspects of the formation of the components labeled by radioactive amino acids in isolated mitochondria of rat liver and Zajdela hepatoma were studied. Isolated mitochondria were labeled with radioactive amino acids under various conditions, and the distribution of radioactivity in sodium dodecylsulfate-polyacrylamide gels after electrophoresis of mitochondrial membrane fraction was analysed. 1. Isolated mitochondria of rat liver and Zajdela hepatoma incroporated radioactive amino acids almost exclusively into the membrane fraction. Electrophoretic analysis of this fraction revealed the presence of 15 distinct peaks of radioactivity with corresponding apparent molecular weights of 10 000 to 58 000. The electrophoretic mobility of the labeled components was identical and the general pattern of the radioactivity distribution in the gel for the rat liver and the tumour mitochondria was very similar. 2. Components of the membrane fraction of rat liver mitochondria labeled in vitro displayed an unequal solubility in acidic (2 mM HC1) chloroform/methanol (2/1) mixture; as detected by sodium dodecylsulfate-polyacrylamide gel electrophoresis a single labeled component with apparent molecular weight of 10 000 was soluble in neutral chloroform/methanol. 3. Inverse relation was observed between amino acid incorporation activity of isolated mitochondria and the portion of the label incorporated into the component with apparent molecular weight 10 000. The identity of this component with that soluble in neutral chloroform/methanol mixture has been indicated. 4. The rate of incorporation of [3H]leucine by isolated Zajdela hepatoma mitochondria into the components with lower (10 000-25 000) apparent molecular weights decreased with time, whereas that into components with higher (above 25 000) apparent molecular weight remained approximately constant within the time interval tested (30 min). 5. From the total radioactivity incorporated into the membrane fraction during 5-min pulse labeling of isolated Zajdela hepatoma mitochondria by [3H]leucine up to 25% was recovered in the region of the gel corresponding to a component with apparent molecular weight 10 000. After 25 min chase the radioactivity in this region decreased about 3.5 times while the specific radioactivity of the total membrane fraction did not change significantly. The pattern of radioactivity distribution observed after the pulse was preserved by chloramphenicol. 6. Unlabeled sonicated mitochondria or postribosomal supernatant from rat liver regenerating in the presence of chloramphenicol were incubated with neutral chloroform/methanol extract of in vitro with [14C]leucine labeled rat liver mitochondria. After this incubation several labeled components with apparent molecular weights above 10 000 were recovered in the electrophoreograms of the originally unlabeled fractions.", "contents": "Formation, size, and solubility in chloroform/methanol of products of protein synthesis in isolated mitochondria of rat liver and Zajdela hepatoma. The number, size, solubility in chloroform/methanol and some aspects of the formation of the components labeled by radioactive amino acids in isolated mitochondria of rat liver and Zajdela hepatoma were studied. Isolated mitochondria were labeled with radioactive amino acids under various conditions, and the distribution of radioactivity in sodium dodecylsulfate-polyacrylamide gels after electrophoresis of mitochondrial membrane fraction was analysed. 1. Isolated mitochondria of rat liver and Zajdela hepatoma incroporated radioactive amino acids almost exclusively into the membrane fraction. Electrophoretic analysis of this fraction revealed the presence of 15 distinct peaks of radioactivity with corresponding apparent molecular weights of 10 000 to 58 000. The electrophoretic mobility of the labeled components was identical and the general pattern of the radioactivity distribution in the gel for the rat liver and the tumour mitochondria was very similar. 2. Components of the membrane fraction of rat liver mitochondria labeled in vitro displayed an unequal solubility in acidic (2 mM HC1) chloroform/methanol (2/1) mixture; as detected by sodium dodecylsulfate-polyacrylamide gel electrophoresis a single labeled component with apparent molecular weight of 10 000 was soluble in neutral chloroform/methanol. 3. Inverse relation was observed between amino acid incorporation activity of isolated mitochondria and the portion of the label incorporated into the component with apparent molecular weight 10 000. The identity of this component with that soluble in neutral chloroform/methanol mixture has been indicated. 4. The rate of incorporation of [3H]leucine by isolated Zajdela hepatoma mitochondria into the components with lower (10 000-25 000) apparent molecular weights decreased with time, whereas that into components with higher (above 25 000) apparent molecular weight remained approximately constant within the time interval tested (30 min). 5. From the total radioactivity incorporated into the membrane fraction during 5-min pulse labeling of isolated Zajdela hepatoma mitochondria by [3H]leucine up to 25% was recovered in the region of the gel corresponding to a component with apparent molecular weight 10 000. After 25 min chase the radioactivity in this region decreased about 3.5 times while the specific radioactivity of the total membrane fraction did not change significantly. The pattern of radioactivity distribution observed after the pulse was preserved by chloramphenicol. 6. Unlabeled sonicated mitochondria or postribosomal supernatant from rat liver regenerating in the presence of chloramphenicol were incubated with neutral chloroform/methanol extract of in vitro with [14C]leucine labeled rat liver mitochondria. After this incubation several labeled components with apparent molecular weights above 10 000 were recovered in the electrophoreograms of the originally unlabeled fractions."}
{"id": "PMID:241645", "title": "Enzymic properties of nitrated alpha-chymotrypsin and delta-chymotrypsin.", "content": "Chymotrypsinogen A and alpha-chymotrypsin are both nitrated at tyrosines 146 and 171 by reaction with tetranitromethane. This substitution was essentially without influence on the overall rate constant for hydrolyses of N-acetyl-L-tryptophan methyl ester and N-acetyl-L-tyrosine ethyl ester catalyzed by alpha-chymotrypsin and delta-chymotrypsin, prepared by fast tryptic activation of nitrated chymotrypsinogen. With both ester substrates Km was doubled for nitrated alpha-chymotrypsin. Nitrated alpha-chymotrypsin, nitrated delta-chymotrypsin and delta-chymotrypsin could all bind N-acetyl-L-tryptophan methyl ester at alkaline pH, in contrast to alpha-chymotrypsin. The dissociation constant, Kd, of the complex of alpha-chymotrypsin and basic pancreatic trypsin inhibitor was lowered ten-fold relative to the constant obtained with unmodified alpha-chymotrypsin. The nitrated delta-chymotrypsin and delta-chymotrypsin showed identical Kd values. The nitrated alpha-chymotrypsin is inactivated faster at pH 8.0 and 8.5 than alpha-chymotrypsin and apparently by a different mechanism.", "contents": "Enzymic properties of nitrated alpha-chymotrypsin and delta-chymotrypsin. Chymotrypsinogen A and alpha-chymotrypsin are both nitrated at tyrosines 146 and 171 by reaction with tetranitromethane. This substitution was essentially without influence on the overall rate constant for hydrolyses of N-acetyl-L-tryptophan methyl ester and N-acetyl-L-tyrosine ethyl ester catalyzed by alpha-chymotrypsin and delta-chymotrypsin, prepared by fast tryptic activation of nitrated chymotrypsinogen. With both ester substrates Km was doubled for nitrated alpha-chymotrypsin. Nitrated alpha-chymotrypsin, nitrated delta-chymotrypsin and delta-chymotrypsin could all bind N-acetyl-L-tryptophan methyl ester at alkaline pH, in contrast to alpha-chymotrypsin. The dissociation constant, Kd, of the complex of alpha-chymotrypsin and basic pancreatic trypsin inhibitor was lowered ten-fold relative to the constant obtained with unmodified alpha-chymotrypsin. The nitrated delta-chymotrypsin and delta-chymotrypsin showed identical Kd values. The nitrated alpha-chymotrypsin is inactivated faster at pH 8.0 and 8.5 than alpha-chymotrypsin and apparently by a different mechanism."}
{"id": "PMID:241646", "title": "Mitochondria and peroxisomes from the cellular slime mould Dictyostelium discoideum. Isolation techniques and urate oxidase association with peroxisomes.", "content": "The isolation of cell organelles from Dictyostelium discoideum was attempted using a variety of techniques. Cell homogenization (e.g. Potter-Elvehjem, glass beads) gave poor yields of organelles which were, in addition, exceptionally fragile and unstable in density gradients. An isolation method was developed using Triton X-100 in buffered sorbitol/Ficoll solutions at concentrations optimal for plasma membrane rupture. Immediately following cell lysis the solutions were diluted to sub-optimal Triton X-100 concentrations. Sedimentabilities of malate dehydrogenase, citrate synthetase, urate oxidase and catalase of around 55%, 40%, 35% and 55% respectively could be demonstrated using this method. The organelles were more resistant to breakage during resuspension following differential centrifugation and remained largely intact during density gradient centrifugation. The distribution of adenylate kinase activity in gradients showed that at least half the mitochondria retained an intact outer membrane. The mitochondria and peroxisomes could not be clearly separated using conventional sucrose-Ficoll density gradients. Separation was achieved by incubating the cell homogenate with succinate and a tetrazolium dye (2-p-iodophenyl-3-p-nitrophenyl-5-phenyl monotetrazolium chloride). Succinate dehydrogenase activity of mitochondria reduced the tetrazolium dye and the product (formazan) was deposited on the mitochondrial membranes (\"heavy-labelling\"). The mitochondria then sedimented to denser regions of the gradient while catalase distribution remained unchanged. The treatment left both organelles intact. The mitochondria (1.21 g/ml) were slightly denser than the peroxisomes (1.19 g/ml). The peroxisomes contained catalase and urate oxidase; no other hydrogen-peroxide-producing oxidases were detected. The slime mould urate oxidase resembled the mammalian enzyme. It had an apparent Km value of 12.5 muM, an optimum of activity at pH 8.5 in borate buffer and was competitively inhibited by trichloropurine.", "contents": "Mitochondria and peroxisomes from the cellular slime mould Dictyostelium discoideum. Isolation techniques and urate oxidase association with peroxisomes. The isolation of cell organelles from Dictyostelium discoideum was attempted using a variety of techniques. Cell homogenization (e.g. Potter-Elvehjem, glass beads) gave poor yields of organelles which were, in addition, exceptionally fragile and unstable in density gradients. An isolation method was developed using Triton X-100 in buffered sorbitol/Ficoll solutions at concentrations optimal for plasma membrane rupture. Immediately following cell lysis the solutions were diluted to sub-optimal Triton X-100 concentrations. Sedimentabilities of malate dehydrogenase, citrate synthetase, urate oxidase and catalase of around 55%, 40%, 35% and 55% respectively could be demonstrated using this method. The organelles were more resistant to breakage during resuspension following differential centrifugation and remained largely intact during density gradient centrifugation. The distribution of adenylate kinase activity in gradients showed that at least half the mitochondria retained an intact outer membrane. The mitochondria and peroxisomes could not be clearly separated using conventional sucrose-Ficoll density gradients. Separation was achieved by incubating the cell homogenate with succinate and a tetrazolium dye (2-p-iodophenyl-3-p-nitrophenyl-5-phenyl monotetrazolium chloride). Succinate dehydrogenase activity of mitochondria reduced the tetrazolium dye and the product (formazan) was deposited on the mitochondrial membranes (\"heavy-labelling\"). The mitochondria then sedimented to denser regions of the gradient while catalase distribution remained unchanged. The treatment left both organelles intact. The mitochondria (1.21 g/ml) were slightly denser than the peroxisomes (1.19 g/ml). The peroxisomes contained catalase and urate oxidase; no other hydrogen-peroxide-producing oxidases were detected. The slime mould urate oxidase resembled the mammalian enzyme. It had an apparent Km value of 12.5 muM, an optimum of activity at pH 8.5 in borate buffer and was competitively inhibited by trichloropurine."}
{"id": "PMID:241647", "title": "The effect of pH on the kinetics of beef-liver fructose bisphosphatase.", "content": "1. The kinetics of the reaction catalysed by fructose bisphosphatase have been studied at pH 7.2 and at pH 9.5. The activity of the enzyme was shown to respond sigmoidally to increasing concentrations of free Mg2+ or Mn2+ ions at pH 7.2, whereas the dependence was hyperbolic at pH 9.5. At both pH values the enzyme responded hyperbolically to increasing concentrations of fructose 1,6-bisphosphate, although inhibition was observed at higher concentrations of this substrate. This high substrate inhibition was shown to be partial in nature and the enzyme was found to be more sensitive at pH 7.2 than at pH 9.5. 2. The properties of the enzyme, are consistent with the enzyme obeying either a random-order equilibrium mechanism or a compulsory-order steady-state mechanism in which fructose bisphosphate binds to the enzyme before the cation. 3. Reaction of the enzyme with a four-fold molar excess of p-chloromercuribenzoate caused activation of the enzyme when its activity was assayed in the presence of MN2+ ions but inhibition when Mg2+ ions were used. Higher concentrations of p-chloromercuribenzoate caused inhibition. This activation at low p-chloromercuribenzoate concentrations, and the reaction of 5,5'-dithio-bis(2-nitrobenzoate) with the four thiol groups in the enzyme that reacted rapidly with this reagent, were prevented or slowed by the presence of inhibitory, but not non-inhibitory, concentrations of fructose bisphosphate. After reaction with a four-fold molar excess of p-chloromercuribenzoate the enzyme was no longer sensitive to high substrate inhibition by fructose bisphosphate.", "contents": "The effect of pH on the kinetics of beef-liver fructose bisphosphatase. 1. The kinetics of the reaction catalysed by fructose bisphosphatase have been studied at pH 7.2 and at pH 9.5. The activity of the enzyme was shown to respond sigmoidally to increasing concentrations of free Mg2+ or Mn2+ ions at pH 7.2, whereas the dependence was hyperbolic at pH 9.5. At both pH values the enzyme responded hyperbolically to increasing concentrations of fructose 1,6-bisphosphate, although inhibition was observed at higher concentrations of this substrate. This high substrate inhibition was shown to be partial in nature and the enzyme was found to be more sensitive at pH 7.2 than at pH 9.5. 2. The properties of the enzyme, are consistent with the enzyme obeying either a random-order equilibrium mechanism or a compulsory-order steady-state mechanism in which fructose bisphosphate binds to the enzyme before the cation. 3. Reaction of the enzyme with a four-fold molar excess of p-chloromercuribenzoate caused activation of the enzyme when its activity was assayed in the presence of MN2+ ions but inhibition when Mg2+ ions were used. Higher concentrations of p-chloromercuribenzoate caused inhibition. This activation at low p-chloromercuribenzoate concentrations, and the reaction of 5,5'-dithio-bis(2-nitrobenzoate) with the four thiol groups in the enzyme that reacted rapidly with this reagent, were prevented or slowed by the presence of inhibitory, but not non-inhibitory, concentrations of fructose bisphosphate. After reaction with a four-fold molar excess of p-chloromercuribenzoate the enzyme was no longer sensitive to high substrate inhibition by fructose bisphosphate."}
{"id": "PMID:241648", "title": "Active enhancement of heart transplants in the inbred rat with donor strain blood.", "content": "Prolongation of survival time of heart transplants in inbred rats following intravenous injection of donor strain blood according to various time-dose schedules is described. The immunological status of long-term survivors shows detectable antidonor antibodies, normal graft-versus-host reactions and rejection of skin grafts in the usual time. Lymphocytotoxic activity is well related to the survival time of the heart in those rats which respond to the treatment.", "contents": "Active enhancement of heart transplants in the inbred rat with donor strain blood. Prolongation of survival time of heart transplants in inbred rats following intravenous injection of donor strain blood according to various time-dose schedules is described. The immunological status of long-term survivors shows detectable antidonor antibodies, normal graft-versus-host reactions and rejection of skin grafts in the usual time. Lymphocytotoxic activity is well related to the survival time of the heart in those rats which respond to the treatment."}
{"id": "PMID:241649", "title": "Observations on the effect of CO2 and temperature on the sickling phenomenon.", "content": "The explanation of the effect of CO2 on the sickling phenomenon has, in the past, been based solely on the alteration of the oxygen affinity of haemoglobin induced by the CO2, and hence solely on the oxygen saturation of the haemoglobin. A re-investigation of this phenomenon, reported here, shows that this explanation is inadequate; rather, a full explanation requires the use of Perutz's hypothesis that the haemoglobin molecule can exist in various conformationally distinct states, the relative concentrations of which are dependent not only on the oxygen saturation of the molecules but also on other factors such as pH and 2,3-diphosphoglycerate (DPG) concentration. The effect of temperature on the sickling phenomenon is explained in a similar fashion. Low temperature is found to have no effect on the morphology of irreversibly sickled cells.", "contents": "Observations on the effect of CO2 and temperature on the sickling phenomenon. The explanation of the effect of CO2 on the sickling phenomenon has, in the past, been based solely on the alteration of the oxygen affinity of haemoglobin induced by the CO2, and hence solely on the oxygen saturation of the haemoglobin. A re-investigation of this phenomenon, reported here, shows that this explanation is inadequate; rather, a full explanation requires the use of Perutz's hypothesis that the haemoglobin molecule can exist in various conformationally distinct states, the relative concentrations of which are dependent not only on the oxygen saturation of the molecules but also on other factors such as pH and 2,3-diphosphoglycerate (DPG) concentration. The effect of temperature on the sickling phenomenon is explained in a similar fashion. Low temperature is found to have no effect on the morphology of irreversibly sickled cells."}
{"id": "PMID:241650", "title": "Changes in potassium content of erythrocytes during exercise in man.", "content": "Factors affecting erythrocyte K+ content and plasma electrolytes during light exercise were examined in 8 normal subjects and 27 patients with chronic obstructive lung disease. The patients were classified into bronchitis, emphysema and intermediate groups. Arterial blood was obtained during rest, after 2, 5, and 7 min. of exercise on a bicycle ergometer (30 km/h without mechanical brake), and at 10 and 20 min. during recovery for analysis of PO2, PCO2, plasma H+, Na+, K+, and Cl(-), erythrocyte K+ content and whole blood lactate. Plasma H+ increased significantly in all subjects after 2 min. of exercise and PCO2 rose in normal, bronchitis, and emphysema groups during exercise, whereas PO2 did not change significantly. Plasma K+ rose promptly after the beginning of exercise and remained at high values during exercise. The rapid rise in PCO2 was associated with a significant decrease of calculated erythrocyte K+ in patients with chronic bronchitis. Although changes in plasma H+ were dependent on both PCO2 and lactate, erythrocyte K+ changes were significantly related only to changes in PCO2. These results indicate that the decrease in erythrocyte K+ is mainly controlled by changes in arterial PCO2 during light exercise in patients with chronic bronchitis.", "contents": "Changes in potassium content of erythrocytes during exercise in man. Factors affecting erythrocyte K+ content and plasma electrolytes during light exercise were examined in 8 normal subjects and 27 patients with chronic obstructive lung disease. The patients were classified into bronchitis, emphysema and intermediate groups. Arterial blood was obtained during rest, after 2, 5, and 7 min. of exercise on a bicycle ergometer (30 km/h without mechanical brake), and at 10 and 20 min. during recovery for analysis of PO2, PCO2, plasma H+, Na+, K+, and Cl(-), erythrocyte K+ content and whole blood lactate. Plasma H+ increased significantly in all subjects after 2 min. of exercise and PCO2 rose in normal, bronchitis, and emphysema groups during exercise, whereas PO2 did not change significantly. Plasma K+ rose promptly after the beginning of exercise and remained at high values during exercise. The rapid rise in PCO2 was associated with a significant decrease of calculated erythrocyte K+ in patients with chronic bronchitis. Although changes in plasma H+ were dependent on both PCO2 and lactate, erythrocyte K+ changes were significantly related only to changes in PCO2. These results indicate that the decrease in erythrocyte K+ is mainly controlled by changes in arterial PCO2 during light exercise in patients with chronic bronchitis."}
{"id": "PMID:241651", "title": "The effect of propranolol and phentolamine on serum gastrin concentration in response to respiratory acidosis in normal man.", "content": "Serum gastrin concentration and basal acid secretion were studied in normal subjects under the influence of respiratory acidosis induced by CO2 rebreathing. During the intragastric instillation of 100 ml/h 0.5 M bicarbonate a significant increase of gastrinaemia from 133 to 158 pg/ml (p less than 0.01) occurred in ten subjects during respiratory acidosis (pCO2 62 torr, pH 7.25). Under the intragastric instillation of 100 ml/h 0.1 N HCl the rise of gastrin concentration in response to CO2 rebreathing (pCO2 68 torr, pH 7.20) was not significant. The relationship between the decrease of pH and the increase of the gastrin concentration was shifted in the direction of a greater systemic acidosis compared to the results performed in the presence of a neutral intragastric pH. 50 mug/kg propranolol intravenously produced a decrease of gastrin concentrations from 145 to 127 pg/ml (p less than 0.01) and a total suppression of hypergastrinaemia in response to CO2 rebreathing, suggesting activation of beta-cell receptors in respiratory acidosis. The infusion of phentolamine in a dose of 0.6 to 1.8 mg/min. resulted in a rise of gastrin concentration from 140 to 165 pg/ml (p less than 0.01) which was not further elevated during respiratory acidosis. The basal acid secretion showed a significant rise in response to CO2 rebreathing, which was abolished by the administration of propranolol.", "contents": "The effect of propranolol and phentolamine on serum gastrin concentration in response to respiratory acidosis in normal man. Serum gastrin concentration and basal acid secretion were studied in normal subjects under the influence of respiratory acidosis induced by CO2 rebreathing. During the intragastric instillation of 100 ml/h 0.5 M bicarbonate a significant increase of gastrinaemia from 133 to 158 pg/ml (p less than 0.01) occurred in ten subjects during respiratory acidosis (pCO2 62 torr, pH 7.25). Under the intragastric instillation of 100 ml/h 0.1 N HCl the rise of gastrin concentration in response to CO2 rebreathing (pCO2 68 torr, pH 7.20) was not significant. The relationship between the decrease of pH and the increase of the gastrin concentration was shifted in the direction of a greater systemic acidosis compared to the results performed in the presence of a neutral intragastric pH. 50 mug/kg propranolol intravenously produced a decrease of gastrin concentrations from 145 to 127 pg/ml (p less than 0.01) and a total suppression of hypergastrinaemia in response to CO2 rebreathing, suggesting activation of beta-cell receptors in respiratory acidosis. The infusion of phentolamine in a dose of 0.6 to 1.8 mg/min. resulted in a rise of gastrin concentration from 140 to 165 pg/ml (p less than 0.01) which was not further elevated during respiratory acidosis. The basal acid secretion showed a significant rise in response to CO2 rebreathing, which was abolished by the administration of propranolol."}
{"id": "PMID:241652", "title": "The role of histamine in burn, tourniquet and endotoxin shock in mice.", "content": "The release of histamine and mortality was studied in mice after various types of experimental shock. In burn shock, serum histamine rose significantly after injury, but there was no correlation between increased serum histamine and high mortality as a consequence of several therapy regimens. For example, after treatment with histamine or Compound 48/80 before burning, there was a rise of serum histamine, yet shock mortality fell significantly. Although separate administration of antagonists of H1 - or H2 - histamine receptors had no effect on mortality, pretreatment with both diphenhydramine and burimamide significantly increased shock mortality. In tourniquet shock, serum histamine rose significantly, and treatment with both antagonists before trauma produced a significant elevation of shock mortality. In endotoxin shock, prior treatment with one or both drugs did not change mortality. These results suggest that endogenous histamine is not a lethal factor in burn and tourniquet trauma, but rather it appears to have a compensatory, beneficial effect.", "contents": "The role of histamine in burn, tourniquet and endotoxin shock in mice. The release of histamine and mortality was studied in mice after various types of experimental shock. In burn shock, serum histamine rose significantly after injury, but there was no correlation between increased serum histamine and high mortality as a consequence of several therapy regimens. For example, after treatment with histamine or Compound 48/80 before burning, there was a rise of serum histamine, yet shock mortality fell significantly. Although separate administration of antagonists of H1 - or H2 - histamine receptors had no effect on mortality, pretreatment with both diphenhydramine and burimamide significantly increased shock mortality. In tourniquet shock, serum histamine rose significantly, and treatment with both antagonists before trauma produced a significant elevation of shock mortality. In endotoxin shock, prior treatment with one or both drugs did not change mortality. These results suggest that endogenous histamine is not a lethal factor in burn and tourniquet trauma, but rather it appears to have a compensatory, beneficial effect."}
{"id": "PMID:241653", "title": "Centrally induced hypotensive effects of beta-adrenergic blocking drugs.", "content": "The mechanism of the antihypertensive effects of propranolol, pindolol and sotalol were investigated using chloralose-anesthetized cats and dogs. When administered i.v. into a carotid or vertebral artery, propranolol was readily taken up by several brain areas. Highest drug concentrations were detected in the hypothalamus and its projection areas and low concentrations in the cerebral cortex and peripheral tissues. Discrete drug administration at several brain sites decreased efferent sympathetic but increased efferent parasympathetic nerve activity. These neural changes were associated with reductions in both blood pressure and heart rate. Hippocampal propranolol administration induced the greatest neural and cardiovascular changes. Significant concurrent reductions in blood pressure, heart rate and cardiac contractile force occurred following propranolol (500 mug) administration into the hippocampus and pindolol (80 mug) administration into the septum. Sotalo injections at various brain sites failed to influence the cardiovascular system. The centrally induced cardiovascular and neural changes induced by both propranolol and pindolol were prevented by pretreatment with hexamethonium. These results suggest that the hypotensive effects of both propranolol and pindolol may be related to a reduction in the level of central  autonomic control resulting in decreased levels of blood pressure, heart rate and cardiac contractile force.", "contents": "Centrally induced hypotensive effects of beta-adrenergic blocking drugs. The mechanism of the antihypertensive effects of propranolol, pindolol and sotalol were investigated using chloralose-anesthetized cats and dogs. When administered i.v. into a carotid or vertebral artery, propranolol was readily taken up by several brain areas. Highest drug concentrations were detected in the hypothalamus and its projection areas and low concentrations in the cerebral cortex and peripheral tissues. Discrete drug administration at several brain sites decreased efferent sympathetic but increased efferent parasympathetic nerve activity. These neural changes were associated with reductions in both blood pressure and heart rate. Hippocampal propranolol administration induced the greatest neural and cardiovascular changes. Significant concurrent reductions in blood pressure, heart rate and cardiac contractile force occurred following propranolol (500 mug) administration into the hippocampus and pindolol (80 mug) administration into the septum. Sotalo injections at various brain sites failed to influence the cardiovascular system. The centrally induced cardiovascular and neural changes induced by both propranolol and pindolol were prevented by pretreatment with hexamethonium. These results suggest that the hypotensive effects of both propranolol and pindolol may be related to a reduction in the level of central  autonomic control resulting in decreased levels of blood pressure, heart rate and cardiac contractile force."}
{"id": "PMID:241654", "title": "Neuroleptic antagonism of dyskinetic phenomena.", "content": "The bilateral intrastriatal administration of dopamine to guinea pigs pretreated with nialamide-induced dyskinesias characterized by gnawing, biting and licking reactions, acute twisting of the head and neck, whole body or head and neck rocking movements, and a hyperactive state. Hyperactivity was inhibited by the peripheral administration of large doses of many neuroleptic agents, e.g. haloperidol, fluphenazine, but only pimozide and oxiperomide inhibited the other forms of dyskinetic movements. This was not due to a peculiar depressant effect of these agents in the guinea pig since haloperidol was shown to be equipotent to oxiperomide and of greater potency than pimozide both in causing catalepsy and antagonising amphetamine sterotypy...", "contents": "Neuroleptic antagonism of dyskinetic phenomena. The bilateral intrastriatal administration of dopamine to guinea pigs pretreated with nialamide-induced dyskinesias characterized by gnawing, biting and licking reactions, acute twisting of the head and neck, whole body or head and neck rocking movements, and a hyperactive state. Hyperactivity was inhibited by the peripheral administration of large doses of many neuroleptic agents, e.g. haloperidol, fluphenazine, but only pimozide and oxiperomide inhibited the other forms of dyskinetic movements. This was not due to a peculiar depressant effect of these agents in the guinea pig since haloperidol was shown to be equipotent to oxiperomide and of greater potency than pimozide both in causing catalepsy and antagonising amphetamine sterotypy..."}
{"id": "PMID:241655", "title": "Pharmacology of nadolol (SQ 11725), a beta-adrenergic antagonist lacking direct myocardial depression.", "content": "SQ 11725 was approximately 1/3 as potent as propranolol in blocking the stimulant effects of isoproterenol in vitro, but was 2-4 times more potent than propranolol in blocking the diastolic blood-pressure and heart-rate responses, respectively, to isoproterenol in vivo. SQ 11725 had no depressant effects on contractile force of isolated guinea pig atrial muscle at the largest bath concentration studied (1000 mug/ml), whereas propranolol caused significant depression at a concentration of 1-10 mug/ml. Propranolol was at least 20-30 times more depressant than SQ 11725 to canine myocardium in vivo. SQ 11725 was more effective then propranolol in inhibiting tachycardic responses to treadmill exercise in unanesthetized dogs. The duration of blockade of the heart-rate response to exercise or to isoproterenol administration in the unanesthetized dog was approximately 5 times greater with SQ 11725 than with propranolol.", "contents": "Pharmacology of nadolol (SQ 11725), a beta-adrenergic antagonist lacking direct myocardial depression. SQ 11725 was approximately 1/3 as potent as propranolol in blocking the stimulant effects of isoproterenol in vitro, but was 2-4 times more potent than propranolol in blocking the diastolic blood-pressure and heart-rate responses, respectively, to isoproterenol in vivo. SQ 11725 had no depressant effects on contractile force of isolated guinea pig atrial muscle at the largest bath concentration studied (1000 mug/ml), whereas propranolol caused significant depression at a concentration of 1-10 mug/ml. Propranolol was at least 20-30 times more depressant than SQ 11725 to canine myocardium in vivo. SQ 11725 was more effective then propranolol in inhibiting tachycardic responses to treadmill exercise in unanesthetized dogs. The duration of blockade of the heart-rate response to exercise or to isoproterenol administration in the unanesthetized dog was approximately 5 times greater with SQ 11725 than with propranolol."}
{"id": "PMID:241656", "title": "ACTH-like peptides and opiate receptors in the rat brain: structure-activity studies.", "content": "The present study aims at further identifying the interaction of ACTH-like peptides and rat brain opiate receptors in vitro. The sequence ACTH4-10 is crucial with respect to affinity since it is the shortest sequence to inhibit the binding of [3H]-dihydromorphine and [3H]-naltrexone to these receptors. A second active site seems to be localized in the N-terminal part of ACTH11-24. This structure-activity relationship is compared to that observed for these peptides on the adrenal cortex and behavior.", "contents": "ACTH-like peptides and opiate receptors in the rat brain: structure-activity studies. The present study aims at further identifying the interaction of ACTH-like peptides and rat brain opiate receptors in vitro. The sequence ACTH4-10 is crucial with respect to affinity since it is the shortest sequence to inhibit the binding of [3H]-dihydromorphine and [3H]-naltrexone to these receptors. A second active site seems to be localized in the N-terminal part of ACTH11-24. This structure-activity relationship is compared to that observed for these peptides on the adrenal cortex and behavior."}
{"id": "PMID:241660", "title": "[Characteristics of the combined action of fentanyl and sodium oxybutyrate on respiration].", "content": "Experiments conducted with rabbits (86) and albino rats (28) demonstrated that with the use of sodium oxybutyrate (200 mg/kg) in combination with phentanyl (0,02 mg/kg) the former reduces the depressing influence of the latter on the external respiration and tissue processes.", "contents": "[Characteristics of the combined action of fentanyl and sodium oxybutyrate on respiration]. Experiments conducted with rabbits (86) and albino rats (28) demonstrated that with the use of sodium oxybutyrate (200 mg/kg) in combination with phentanyl (0,02 mg/kg) the former reduces the depressing influence of the latter on the external respiration and tissue processes."}
{"id": "PMID:241661", "title": "[Effect of sodium oxybutyrate, phenamin, transamine and L-dopa on the processes of work capacity recovery under conditions of minimal rest].", "content": "The action of sodium oxybutyrate, phenamine transamine and L-DOPA on the processes of re-establishing the mental and physical performance capacity after fatigue was studied in experiments with rats. The activating effect of sodium oxybutyrate on the resotration of performance capacity in these conditions is shown not to be inferior to an analogous action of phenamine. Complete re-establishment of performance capacity is recorded against the background of the action produced by a monoaminoxidase inhibitor-transamine, as well as combinations of sodium oxybutyrate and L-DOPA.", "contents": "[Effect of sodium oxybutyrate, phenamin, transamine and L-dopa on the processes of work capacity recovery under conditions of minimal rest]. The action of sodium oxybutyrate, phenamine transamine and L-DOPA on the processes of re-establishing the mental and physical performance capacity after fatigue was studied in experiments with rats. The activating effect of sodium oxybutyrate on the resotration of performance capacity in these conditions is shown not to be inferior to an analogous action of phenamine. Complete re-establishment of performance capacity is recorded against the background of the action produced by a monoaminoxidase inhibitor-transamine, as well as combinations of sodium oxybutyrate and L-DOPA."}
{"id": "PMID:241664", "title": "Ergoline derivatives. Note XIII (1) alpha-adrenergic blocking drugs.", "content": "The synthesis and the pharmacological activities of 24 analogues of the alpha-adrenergic blocking drug, nicergoline (I b), are reported. The majority of the new compounds were found to be less active than (I b): the structure-activity relationships are presented and discussed.", "contents": "Ergoline derivatives. Note XIII (1) alpha-adrenergic blocking drugs. The synthesis and the pharmacological activities of 24 analogues of the alpha-adrenergic blocking drug, nicergoline (I b), are reported. The majority of the new compounds were found to be less active than (I b): the structure-activity relationships are presented and discussed."}
{"id": "PMID:241665", "title": "[Antiviral chemotherapeutic agents. XVIII. Adamantane derivatives of amphetamine. Their potential interest as autonomic and antiparkinson agents].", "content": "Adamantane isologs of amphetamine, methamphetamine and pheniprazine and several derivatives were synthesized in order to study the influence of their more pronounced lipophilic characteristics on their biological properties. A preliminary examination of their toxicity, antiviral, CNS stimulant and antiparkinson activity is described. The adamantyl amphetamine, which proved active, will be further studied.", "contents": "[Antiviral chemotherapeutic agents. XVIII. Adamantane derivatives of amphetamine. Their potential interest as autonomic and antiparkinson agents]. Adamantane isologs of amphetamine, methamphetamine and pheniprazine and several derivatives were synthesized in order to study the influence of their more pronounced lipophilic characteristics on their biological properties. A preliminary examination of their toxicity, antiviral, CNS stimulant and antiparkinson activity is described. The adamantyl amphetamine, which proved active, will be further studied."}
{"id": "PMID:241662", "title": "[Effect of steroid hormones on the rate of NADPH and NADH oxidation by rat liver microsomes].", "content": "Sex hormones heighten the rate of the NADP-H oxidation. A relation between the oxidation rate of steroids and the polarity of their molecule has been found. Both androgens and estogens inhibit the transport of electrons in the NAD-H-dependent chain. The capability of steroids to hydrooxylate depends upon the chemical structure and not the affiliation to androgens or estrogens.", "contents": "[Effect of steroid hormones on the rate of NADPH and NADH oxidation by rat liver microsomes]. Sex hormones heighten the rate of the NADP-H oxidation. A relation between the oxidation rate of steroids and the polarity of their molecule has been found. Both androgens and estogens inhibit the transport of electrons in the NAD-H-dependent chain. The capability of steroids to hydrooxylate depends upon the chemical structure and not the affiliation to androgens or estrogens."}
{"id": "PMID:241663", "title": "[Pharmacological and radioprotective properties of some gamma-pyrone derivatives (flavanones and flavanols)].", "content": "In experiments set up on mice, rats and guinea pigs 8 gamma-pyron derivatives were studied. They proved to be little toxic, do not change significantly the arterial pressure and respiration, exercise a depressing action on the central nervous system, produce a marked antiphlogistic (normal and irradiated animals), radio-protective and antihistaminic effects and influence norephinephrine, homovanillic acid and dopamine metabolism in the brain.", "contents": "[Pharmacological and radioprotective properties of some gamma-pyrone derivatives (flavanones and flavanols)]. In experiments set up on mice, rats and guinea pigs 8 gamma-pyron derivatives were studied. They proved to be little toxic, do not change significantly the arterial pressure and respiration, exercise a depressing action on the central nervous system, produce a marked antiphlogistic (normal and irradiated animals), radio-protective and antihistaminic effects and influence norephinephrine, homovanillic acid and dopamine metabolism in the brain."}
{"id": "PMID:241668", "title": "Use of 1,3-butanediol for lactation and growth in cattle.", "content": "These studies have been designed to test whether 1,3-butanediol (BD) alleviates milk fat depression in lactating cows, to observe physiological changes in blood and rumen constituents when BD is fed to cows or growing cattle, and to test the effects of BD on growth rates and feed efficiency in growing cattle. In trials with lactating cows, milk fat percentage and total fat production were higher for cows fed BD than for controls. Feeding BD to either cows or growing cattle had no consistent effect on rumen pH or relative concentrations of rumen volatile fatty acids. 1,3-Butanediol feeding had little effect on blood glucose concentrations. Feeding more than 4% BD in diets sometimes caused increased concentrations of blood ketones. In trials where growing cattle were fed 4% BD, rates of gain and feed efficiency were at least as good as and often better than those of cattle fed the same diets without BD. Body composition was not significantly affected. 1,3-Butanediol can be utilized effectively as an energy source for cattle and causes no obvious problems with 4% in diets.", "contents": "Use of 1,3-butanediol for lactation and growth in cattle. These studies have been designed to test whether 1,3-butanediol (BD) alleviates milk fat depression in lactating cows, to observe physiological changes in blood and rumen constituents when BD is fed to cows or growing cattle, and to test the effects of BD on growth rates and feed efficiency in growing cattle. In trials with lactating cows, milk fat percentage and total fat production were higher for cows fed BD than for controls. Feeding BD to either cows or growing cattle had no consistent effect on rumen pH or relative concentrations of rumen volatile fatty acids. 1,3-Butanediol feeding had little effect on blood glucose concentrations. Feeding more than 4% BD in diets sometimes caused increased concentrations of blood ketones. In trials where growing cattle were fed 4% BD, rates of gain and feed efficiency were at least as good as and often better than those of cattle fed the same diets without BD. Body composition was not significantly affected. 1,3-Butanediol can be utilized effectively as an energy source for cattle and causes no obvious problems with 4% in diets."}
{"id": "PMID:241669", "title": "Prolonged survival of skin allografts in rats treated with antigen and hydrocortisone and the trend in graft-versus-host reactions.", "content": "The mechanism of prolongation of skin allograft survival in rats treated with specific antigen and hydrocortisone was studied in the strain combination with the strong (H-1 + non-H-1) and weak (non-H-1) antigenic difference. The grafts differing from the recipients at the weak non-H-1 loci only showed the longest survival although unresponsiveness to the strong (H-1) antigens of the donor type had already disappeared. In both strain combinations, immunological reactivity of lymphoid cells from treated animals was demonstrated in local GVH reactions at the end of the treatment (i.e., 12 days after transplantation). Lymphoid cells isolated from long surviving (100 days) AVN recipients of non-H-1 different grafts did not react in the GVH test. Attempts to obtain prolongation of skin allograft survival by passive transfer of serum removed after termination of immunization with strong (H-1 + non-H-1) or only weak (non-H-1) antigens were not successful.", "contents": "Prolonged survival of skin allografts in rats treated with antigen and hydrocortisone and the trend in graft-versus-host reactions. The mechanism of prolongation of skin allograft survival in rats treated with specific antigen and hydrocortisone was studied in the strain combination with the strong (H-1 + non-H-1) and weak (non-H-1) antigenic difference. The grafts differing from the recipients at the weak non-H-1 loci only showed the longest survival although unresponsiveness to the strong (H-1) antigens of the donor type had already disappeared. In both strain combinations, immunological reactivity of lymphoid cells from treated animals was demonstrated in local GVH reactions at the end of the treatment (i.e., 12 days after transplantation). Lymphoid cells isolated from long surviving (100 days) AVN recipients of non-H-1 different grafts did not react in the GVH test. Attempts to obtain prolongation of skin allograft survival by passive transfer of serum removed after termination of immunization with strong (H-1 + non-H-1) or only weak (non-H-1) antigens were not successful."}
{"id": "PMID:241673", "title": "Insulin degradation by isolated fat cells and their subcellular fractions.", "content": "Isolated frt cells and purified subcellular fractions of fat cells have been shown to degrade insulin to biologically inactive trichloroacetic-acid-soluble fragments. Further study of this activity has revealed the following characteristics: 1 Most of the insulin-degrading enzymes are intracellular, inaccessible to insulin or trypsin when fat cells are intact. More that 90 per cent of the recovered activity is found in the high-speed supernatant (cytosol) when cell fractionation studies are performed. 2. The plasma membrane contains significant insulin-degradative capacity, as shown by tryptic digestion of intact cells and cell fractionation. 3. The pH optimum of the cell-membrane insulin-degrading site is more acid than that of the cytosol activity, but the tow enzyme systems are similar with regard to substrate specificity, response to metabolic inhibitors, and elution volume of degradation products on gel filtration. 4. The plasma-membrane-degrading activity differs from the specific insulin-binding site with regard to saturation kinetics, optimum temperature, substrate specificity, sensitivity to sulfhydryl-blocking agents, and trypsin snesitivity.", "contents": "Insulin degradation by isolated fat cells and their subcellular fractions. Isolated frt cells and purified subcellular fractions of fat cells have been shown to degrade insulin to biologically inactive trichloroacetic-acid-soluble fragments. Further study of this activity has revealed the following characteristics: 1 Most of the insulin-degrading enzymes are intracellular, inaccessible to insulin or trypsin when fat cells are intact. More that 90 per cent of the recovered activity is found in the high-speed supernatant (cytosol) when cell fractionation studies are performed. 2. The plasma membrane contains significant insulin-degradative capacity, as shown by tryptic digestion of intact cells and cell fractionation. 3. The pH optimum of the cell-membrane insulin-degrading site is more acid than that of the cytosol activity, but the tow enzyme systems are similar with regard to substrate specificity, response to metabolic inhibitors, and elution volume of degradation products on gel filtration. 4. The plasma-membrane-degrading activity differs from the specific insulin-binding site with regard to saturation kinetics, optimum temperature, substrate specificity, sensitivity to sulfhydryl-blocking agents, and trypsin snesitivity."}
{"id": "PMID:241674", "title": "Behavioural effects of anti-epileptic drugs.", "content": "There is increasing evidence that various types of behavioural disturbance, other than those described for phenytoin, for example, may occur from the use of anti-epileptic medication, and it has been suggested that these disturbances may not always be reversible. There are suspicions also that certain groups of patients--especially those with structural brain damage--are particularly susceptible. These and other factors relevant to the study of the effects of anti-epileptic drugs on behaviour are comprehensively reviewed. It is concluded that the psycho-pharmacology of anti-epileptic drugs is unsatisfactory at present because of inadequate and unsophisticated reporting of behavioural change and because of the common problem of polypharmacy, and that more accurate observations are needed on less heterogeneous groups of patients that have been described in the past.", "contents": "Behavioural effects of anti-epileptic drugs. There is increasing evidence that various types of behavioural disturbance, other than those described for phenytoin, for example, may occur from the use of anti-epileptic medication, and it has been suggested that these disturbances may not always be reversible. There are suspicions also that certain groups of patients--especially those with structural brain damage--are particularly susceptible. These and other factors relevant to the study of the effects of anti-epileptic drugs on behaviour are comprehensively reviewed. It is concluded that the psycho-pharmacology of anti-epileptic drugs is unsatisfactory at present because of inadequate and unsophisticated reporting of behavioural change and because of the common problem of polypharmacy, and that more accurate observations are needed on less heterogeneous groups of patients that have been described in the past."}
{"id": "PMID:241675", "title": "Amino acid decarboxylase enzymes--vital or irrelevant to gastric secretion?", "content": "The location and discovery of histidine decarboxylase and aromatic L-amino acid decarboxylase in the stomach are described. Feeding and gastrin-like agents stimulate increased gastric histidine decarboxylase (HD) acttvity in rats. Procedures which result in increased gastrin release - often by raising antral pH - also have this action in intact but not in antrectomised rats. Evidence for a histaminic feedback mechanism controlling HD levels is discussed. HD activity is reduced by protein synthesis inhibitors and by chronic pyridoxine deficiency. The effects of inhibitors of HD on gastric secretion in rat, dog and man are reviewed. The role of HD and histamine in gastric secretion is considered.", "contents": "Amino acid decarboxylase enzymes--vital or irrelevant to gastric secretion? The location and discovery of histidine decarboxylase and aromatic L-amino acid decarboxylase in the stomach are described. Feeding and gastrin-like agents stimulate increased gastric histidine decarboxylase (HD) acttvity in rats. Procedures which result in increased gastrin release - often by raising antral pH - also have this action in intact but not in antrectomised rats. Evidence for a histaminic feedback mechanism controlling HD levels is discussed. HD activity is reduced by protein synthesis inhibitors and by chronic pyridoxine deficiency. The effects of inhibitors of HD on gastric secretion in rat, dog and man are reviewed. The role of HD and histamine in gastric secretion is considered."}
{"id": "PMID:241676", "title": "Role of gamma-glutamyl transpeptidase activity in the diagnosis of hepatobiliary disease.", "content": "The enzyme gamma-glutamyl transpeptidase is widely distributed throughout the body, notably kidney, seminal vesicles, pancreas, liver, spleen and brain. Being one of the enzymes of the gamma-glutamyl cycle, it is involved in aminoacid transport, catalysing a transpeptidation reaction between gamma-glutamyl peptides and most common amino acids. Methods of assay of the enzyme are based on its ability also to act on synthetic amides of glutamic acid; kinetic methods monitoring the release of p-nitroaniline from the substrate L-gamma-glutamyl p-nitroanilide are the most satisfactory. In diseases of the liver, the highest levels occur in association with cirrhosis, alcoholism, hepatic secondaries and cholestasis. As the enzyme is present in the endoplasmic reticulum of the hepatocyte, its activity is increased in situations leading to microsomal enzyme induction. Raised levels can also occur in pancreatitis, diabetes, myocardial infarction, congestive cardiac failure, chronic renal failure, cerebrovascular accidents, cerebral tumours and chronic obstructive pulmonary disease. Although the lack of specificity must be recognised, the estimation can be useful in the elucidation of some clearly defined problems arising during investigation of patients with suspected hepatic disease, especially where performed as part of a biochemical profile.", "contents": "Role of gamma-glutamyl transpeptidase activity in the diagnosis of hepatobiliary disease. The enzyme gamma-glutamyl transpeptidase is widely distributed throughout the body, notably kidney, seminal vesicles, pancreas, liver, spleen and brain. Being one of the enzymes of the gamma-glutamyl cycle, it is involved in aminoacid transport, catalysing a transpeptidation reaction between gamma-glutamyl peptides and most common amino acids. Methods of assay of the enzyme are based on its ability also to act on synthetic amides of glutamic acid; kinetic methods monitoring the release of p-nitroaniline from the substrate L-gamma-glutamyl p-nitroanilide are the most satisfactory. In diseases of the liver, the highest levels occur in association with cirrhosis, alcoholism, hepatic secondaries and cholestasis. As the enzyme is present in the endoplasmic reticulum of the hepatocyte, its activity is increased in situations leading to microsomal enzyme induction. Raised levels can also occur in pancreatitis, diabetes, myocardial infarction, congestive cardiac failure, chronic renal failure, cerebrovascular accidents, cerebral tumours and chronic obstructive pulmonary disease. Although the lack of specificity must be recognised, the estimation can be useful in the elucidation of some clearly defined problems arising during investigation of patients with suspected hepatic disease, especially where performed as part of a biochemical profile."}
{"id": "PMID:241677", "title": "Localization of 5'-ribonucleotide phosphohydrolase in regenerating (and normal) limb tissues of the adult newt Notophthalmus viridescens.", "content": "The regenerating forelimb of the adult newt, Notophthalmus viridescens was investigated for 5'-nucleotidase (5' ribonucleotide phosphohydrolase, 3.1.3.5) acitivity. The newt's humeri were surgically removed, and after a twenty-one-day recovery period, the forelimbs amputated above the elbows. Regenerates were sampled at predetermined times for specific phases in the progress of regeneration, frozen, sectioned in a cryostat, and the sections fixed in 10% cold formol calcium. The Wachstein and Meisel [25] lead procedure at neutral pH was used predominately in these experiments, although tests were also conducted with Gomori's [14] calcium, Allen's [21] highly alkaline procedures. The substrates used to obtain specific enzyme reactions were adenine, cytosine, guanine, uracil and inosine 5'-monophosphate nucleotides. Sodium beta-glycerophosphate served as a non-specific phosphomonoesterase substrate, distilled water replaced substrate, and inhibitors such as zinc and cyanide ions were used as control measures to assist in increasing the precision in interpreting the results obtained. The most reactive 5'-nucleotidase (5'-Nase) loci were in the walls of the blood vascular system, mysial and neural sheaths, dermis, and periosteum: the principal cells involved were macrophages, endothelium of blood vessels, and fibrocytes of connective tissues. A moderate enzyme response was elicited from secretory cells of some of the subcutaneous glands, hypertrophied chondrocytes and osteogenic centers, chondrocytes in the articular regions and within red blood cells and leucocytes. Normal, injured and degenerating, or regenerating striated muscle and nerve fibers were judged unreactive for 5'-Nase. The epidermis and wound epithelium displayed negative responses for 5'-Nase. Cells forming the regeneration blastema were 5'-Nase reactive during the early formative phase, but with growth and development of the blastema into bulb and conic forms, these cells did not respond for this enzyme-activity. One suggestion offered is that the absence of 5'-Nase in cells of the blastema may be related to the lack of an adequate blood-vascular supply. Several functions of 5'-Nase in normal and regenerating tissues are discussed. A basic conclusion reached is that 5'-nucleotidase hydrolyses may be more involved in fundamental anabolic than in catabolic metabolism.", "contents": "Localization of 5'-ribonucleotide phosphohydrolase in regenerating (and normal) limb tissues of the adult newt Notophthalmus viridescens. The regenerating forelimb of the adult newt, Notophthalmus viridescens was investigated for 5'-nucleotidase (5' ribonucleotide phosphohydrolase, 3.1.3.5) acitivity. The newt's humeri were surgically removed, and after a twenty-one-day recovery period, the forelimbs amputated above the elbows. Regenerates were sampled at predetermined times for specific phases in the progress of regeneration, frozen, sectioned in a cryostat, and the sections fixed in 10% cold formol calcium. The Wachstein and Meisel [25] lead procedure at neutral pH was used predominately in these experiments, although tests were also conducted with Gomori's [14] calcium, Allen's [21] highly alkaline procedures. The substrates used to obtain specific enzyme reactions were adenine, cytosine, guanine, uracil and inosine 5'-monophosphate nucleotides. Sodium beta-glycerophosphate served as a non-specific phosphomonoesterase substrate, distilled water replaced substrate, and inhibitors such as zinc and cyanide ions were used as control measures to assist in increasing the precision in interpreting the results obtained. The most reactive 5'-nucleotidase (5'-Nase) loci were in the walls of the blood vascular system, mysial and neural sheaths, dermis, and periosteum: the principal cells involved were macrophages, endothelium of blood vessels, and fibrocytes of connective tissues. A moderate enzyme response was elicited from secretory cells of some of the subcutaneous glands, hypertrophied chondrocytes and osteogenic centers, chondrocytes in the articular regions and within red blood cells and leucocytes. Normal, injured and degenerating, or regenerating striated muscle and nerve fibers were judged unreactive for 5'-Nase. The epidermis and wound epithelium displayed negative responses for 5'-Nase. Cells forming the regeneration blastema were 5'-Nase reactive during the early formative phase, but with growth and development of the blastema into bulb and conic forms, these cells did not respond for this enzyme-activity. One suggestion offered is that the absence of 5'-Nase in cells of the blastema may be related to the lack of an adequate blood-vascular supply. Several functions of 5'-Nase in normal and regenerating tissues are discussed. A basic conclusion reached is that 5'-nucleotidase hydrolyses may be more involved in fundamental anabolic than in catabolic metabolism."}
{"id": "PMID:241679", "title": "Vascular permeability-increasing action of hypoalbuminemic substance from Ehrlich ascites carcinoma cells.", "content": "A hypoalbuminemic substance (F-3), which was obtained from Ehrlich ascites carcinoma cells, showed a marked vascular permeability-increasing action in mice. The highest increasing effect was produced 20 min after an intradermal injection of F-3. This action was inhibited by diisopropyl fluorophosphate, soybean trypsin inhibitor, and indomethacin but not by hydrocortisone or D-2-bromolysergic acid diethylamide. The inhibition of F-3 by diisopropyl fluorophosphate was observed in partial even after the excess diisopropyl fluorophosphate was removed from the diisopropyl fluorophosphate-treated F-3. The hypoalbuminemic and hypoproteinemic actions were not subjected to any inhibition by the diisopropyl fluorophosphate treatment. The decrease in albumin produced 3 hr after the injection of F-3 would be due to the leakage of albumin from blood vessels. F-3 might contain at least two components, one being a vascular permeability-increasing substance and the other a hypoalbuminemic one.", "contents": "Vascular permeability-increasing action of hypoalbuminemic substance from Ehrlich ascites carcinoma cells. A hypoalbuminemic substance (F-3), which was obtained from Ehrlich ascites carcinoma cells, showed a marked vascular permeability-increasing action in mice. The highest increasing effect was produced 20 min after an intradermal injection of F-3. This action was inhibited by diisopropyl fluorophosphate, soybean trypsin inhibitor, and indomethacin but not by hydrocortisone or D-2-bromolysergic acid diethylamide. The inhibition of F-3 by diisopropyl fluorophosphate was observed in partial even after the excess diisopropyl fluorophosphate was removed from the diisopropyl fluorophosphate-treated F-3. The hypoalbuminemic and hypoproteinemic actions were not subjected to any inhibition by the diisopropyl fluorophosphate treatment. The decrease in albumin produced 3 hr after the injection of F-3 would be due to the leakage of albumin from blood vessels. F-3 might contain at least two components, one being a vascular permeability-increasing substance and the other a hypoalbuminemic one."}
{"id": "PMID:241680", "title": "Induction of ornithine decarboxylase, tyrosine aminotransferase, and thymidine kinase by glucocorticoid in isolated, perfused liver after tumor inoculation.", "content": "A method for producing solid tumors in rat liver or spleen by local inoculation of Yoshida sarcoma or Hirosaki sarcoma was developed by careful selection of rat strains. After development of the tumor, the liver was isolated and perfused with a mixture of calf serum and fluorocarbon. Addition of corticoid hormone to the perfusion fluid induced tyrosine aminotransferase in normal tissue of the liver and to a lesser degree in the tumor tissue. Corticoid did not cause any detectable induction of thymidine kinase in normal tissue of the liver, but caused slight but definite induction of the enzyme in the tumor tissue. Ornithine decarboxylase was induced in the normal tissue by perfusion with serum alone, even without corticoid, but no enzyme induction was observed in the tumor tissue. The low level of this enzyme found in solid tumor tissue might be due to the fact that the enzyme was measured in the late period of tumor growth, because, in experiments with ascites tumor cells, higher enzyme activities were observed in the early period of growth.", "contents": "Induction of ornithine decarboxylase, tyrosine aminotransferase, and thymidine kinase by glucocorticoid in isolated, perfused liver after tumor inoculation. A method for producing solid tumors in rat liver or spleen by local inoculation of Yoshida sarcoma or Hirosaki sarcoma was developed by careful selection of rat strains. After development of the tumor, the liver was isolated and perfused with a mixture of calf serum and fluorocarbon. Addition of corticoid hormone to the perfusion fluid induced tyrosine aminotransferase in normal tissue of the liver and to a lesser degree in the tumor tissue. Corticoid did not cause any detectable induction of thymidine kinase in normal tissue of the liver, but caused slight but definite induction of the enzyme in the tumor tissue. Ornithine decarboxylase was induced in the normal tissue by perfusion with serum alone, even without corticoid, but no enzyme induction was observed in the tumor tissue. The low level of this enzyme found in solid tumor tissue might be due to the fact that the enzyme was measured in the late period of tumor growth, because, in experiments with ascites tumor cells, higher enzyme activities were observed in the early period of growth."}
{"id": "PMID:241681", "title": "Aryl hydrocarbon hydroxylase in liver nuclei of C3H/He and DBA/2 mice.", "content": "Aryl hydrocarbon hydroxylase activity in liver nuclei from C3H/He mice is apparently increased by the administration of 3-methylcholanthrene, but the enzyme activity from the DBA/2 mice is not. On the other hand, by treatment of the mice with phenobarbital sodium, the increased activity in liver nuclei was observed in both strains of mice. There are approximately the same levels of the apparent Km for benzo[alpha]pyrene in liver nuclei from both strains of mice even after treatment with 3-methylcholanthrene, but different Km values for NADPH and NADH are observed between the constitutive and induced enzyme, showing 0.032 and 0.091 mM for NADPH, and 0.303 and 1.67 mM for NADH, respectively. Both 5, 6- and 7, 8-benzoflavones enhance the activity in the constitutive enzyme, but inhibit it in the induced enzyme non-competitively. Nicotinamide inhibits both enzyme activities in liver nuclei. Cyclohexene oxide and 1, 1, 1-trichloropropane oxide enhance the activity in the induced enzyme, but not in the constitutive enzyme in liver nuclei. The differences in the properties between the contitutive and induced enzymes and between the enzymes in microsomes and in nuclei from mouse liver were discussed briefly.", "contents": "Aryl hydrocarbon hydroxylase in liver nuclei of C3H/He and DBA/2 mice. Aryl hydrocarbon hydroxylase activity in liver nuclei from C3H/He mice is apparently increased by the administration of 3-methylcholanthrene, but the enzyme activity from the DBA/2 mice is not. On the other hand, by treatment of the mice with phenobarbital sodium, the increased activity in liver nuclei was observed in both strains of mice. There are approximately the same levels of the apparent Km for benzo[alpha]pyrene in liver nuclei from both strains of mice even after treatment with 3-methylcholanthrene, but different Km values for NADPH and NADH are observed between the constitutive and induced enzyme, showing 0.032 and 0.091 mM for NADPH, and 0.303 and 1.67 mM for NADH, respectively. Both 5, 6- and 7, 8-benzoflavones enhance the activity in the constitutive enzyme, but inhibit it in the induced enzyme non-competitively. Nicotinamide inhibits both enzyme activities in liver nuclei. Cyclohexene oxide and 1, 1, 1-trichloropropane oxide enhance the activity in the induced enzyme, but not in the constitutive enzyme in liver nuclei. The differences in the properties between the contitutive and induced enzymes and between the enzymes in microsomes and in nuclei from mouse liver were discussed briefly."}
{"id": "PMID:241682", "title": "Serum cobalt-activated acylase and gamma-glutamyl transpeptidase activities in toxic hepatitis.", "content": "Marked activity of cobalt-activated acylase was found in the sera of 33 of 37 patients with acute toxic hepatitis due to poisoning with either amanita mushrooms or chemicals. The activity of the enzyme showed a positive correlation with that of serum transaminases, reached the highest levels on the patient's admission to hospital and within a few days fell rapidly to undetectable levels. Slight acylase activity was observed in the majority of patients intoxicated with drugs or carbon monoxide but was not seen in sera of those poisoned with non-amanita mushrooms who showed no signs of liver injury. Unlike acylase, the serum activity of gamma-glutamyl transpeptidase remained unchanged over the first days of acute toxic hepatitis. The determination of serum cobalt-activated acylase might be of value in the diagnosis of acute liver injury.", "contents": "Serum cobalt-activated acylase and gamma-glutamyl transpeptidase activities in toxic hepatitis. Marked activity of cobalt-activated acylase was found in the sera of 33 of 37 patients with acute toxic hepatitis due to poisoning with either amanita mushrooms or chemicals. The activity of the enzyme showed a positive correlation with that of serum transaminases, reached the highest levels on the patient's admission to hospital and within a few days fell rapidly to undetectable levels. Slight acylase activity was observed in the majority of patients intoxicated with drugs or carbon monoxide but was not seen in sera of those poisoned with non-amanita mushrooms who showed no signs of liver injury. Unlike acylase, the serum activity of gamma-glutamyl transpeptidase remained unchanged over the first days of acute toxic hepatitis. The determination of serum cobalt-activated acylase might be of value in the diagnosis of acute liver injury."}
{"id": "PMID:241688", "title": "[Studies on the stearic acid dehydrogenase in the liver and brain of rats of various ages (author's transl)].", "content": "Tissue slices from the liver and brain of 7-day-old rats incubated with [1-14C]stearic acid desaturate the stearate to oleate. The activities of the two tissues are different but of the same order of magnitude. With increasing age, the activity in the liver increases markedly, while the brain activity decreases. The postmitochondrial supernatant from adult (3-month-old) liver contains 2 to 3 orders of magnitude more stearoyl-CoA dehydrogenase activity than the brain postmitochondrial fraction. The washed microsomal fraction from liver had about the same activity as the postmitochondrial supernatant, but no dehydrogenase activity could be detected in the washed microsomal fraction from the brain. The acyl-CoA synthetase and the palmitoyl-CoA hydrolase activities measured in the washed microsomes from adult brain were both lower than in liver microsomes. The concentration of stearoyl-CoA (the substrate for the stearoyl-CoA dehydrogenase) resulting from the ratio of these activities was too high, however, for the lack of desaturase activity to have been simulated by lack of substrate.", "contents": "[Studies on the stearic acid dehydrogenase in the liver and brain of rats of various ages (author's transl)]. Tissue slices from the liver and brain of 7-day-old rats incubated with [1-14C]stearic acid desaturate the stearate to oleate. The activities of the two tissues are different but of the same order of magnitude. With increasing age, the activity in the liver increases markedly, while the brain activity decreases. The postmitochondrial supernatant from adult (3-month-old) liver contains 2 to 3 orders of magnitude more stearoyl-CoA dehydrogenase activity than the brain postmitochondrial fraction. The washed microsomal fraction from liver had about the same activity as the postmitochondrial supernatant, but no dehydrogenase activity could be detected in the washed microsomal fraction from the brain. The acyl-CoA synthetase and the palmitoyl-CoA hydrolase activities measured in the washed microsomes from adult brain were both lower than in liver microsomes. The concentration of stearoyl-CoA (the substrate for the stearoyl-CoA dehydrogenase) resulting from the ratio of these activities was too high, however, for the lack of desaturase activity to have been simulated by lack of substrate."}
{"id": "PMID:241689", "title": "Reduced ferredoxin: CO2 oxidoreductase from Clostridium pasteurianum. Effect of ligands to transition metals on the activity and the stability of the enzyme.", "content": "Reduced ferredoxin: CO2 oxidoreductase (CO2-reductase) from Clostridium pasteurianum catalyzes the reduction of CO2 to formate at the expense of reduced ferredoxin, an isotopic exchange between CO2 and formate in the absence of ferredoxin, and the oxidation of formate to CO2 with oxidized ferredoxin. The three activities were found to be equally affected by monovalent anions known to be ligands to transition metals: The enzyme was reversibly inhibited by azide (Ki = 0.004mM), cyanate (Ki = 0.3 mM), thiocyanate (Ki = 1mM), nitrite (Ki = 0.4mM), nitrate (Ki = 6mM), chlorate (Ki = 3mM), fluoride (Ki = 5mM), and by chloride, bromide, iodide (Ki greater than 5mM). There was no observable effect of pH on the inhibition constants. The enzyme was not inhibited by carbon monoxide. The enzyme was irreversibly inactivated by low concentrations (10muM) of cyanide. The rate of inactivation increased with increasing pH with an inflection point near pH 9.5. Reduced ferredoxin and formate rather than oxidized ferredoxin or CO2 protected the enzyme from inactivation by cyanide. The enzyme was protected by azide and cyanate from inactivation. In the presence of high concentrations of the monovalent anions the rate of inactivation by heat (55 degrees C), by molecular oxygen, and by cyanide was decreased by a factor of more than 100. Half maximal protection was observed at the Ki concentrations of the two reversible inhibitors. The data are interpreted to indicate that a transition metal of weak \"a class\" character and a disulfide are catalytically significant groups of CO2-reductase from C. pasteurianum.", "contents": "Reduced ferredoxin: CO2 oxidoreductase from Clostridium pasteurianum. Effect of ligands to transition metals on the activity and the stability of the enzyme. Reduced ferredoxin: CO2 oxidoreductase (CO2-reductase) from Clostridium pasteurianum catalyzes the reduction of CO2 to formate at the expense of reduced ferredoxin, an isotopic exchange between CO2 and formate in the absence of ferredoxin, and the oxidation of formate to CO2 with oxidized ferredoxin. The three activities were found to be equally affected by monovalent anions known to be ligands to transition metals: The enzyme was reversibly inhibited by azide (Ki = 0.004mM), cyanate (Ki = 0.3 mM), thiocyanate (Ki = 1mM), nitrite (Ki = 0.4mM), nitrate (Ki = 6mM), chlorate (Ki = 3mM), fluoride (Ki = 5mM), and by chloride, bromide, iodide (Ki greater than 5mM). There was no observable effect of pH on the inhibition constants. The enzyme was not inhibited by carbon monoxide. The enzyme was irreversibly inactivated by low concentrations (10muM) of cyanide. The rate of inactivation increased with increasing pH with an inflection point near pH 9.5. Reduced ferredoxin and formate rather than oxidized ferredoxin or CO2 protected the enzyme from inactivation by cyanide. The enzyme was protected by azide and cyanate from inactivation. In the presence of high concentrations of the monovalent anions the rate of inactivation by heat (55 degrees C), by molecular oxygen, and by cyanide was decreased by a factor of more than 100. Half maximal protection was observed at the Ki concentrations of the two reversible inhibitors. The data are interpreted to indicate that a transition metal of weak \"a class\" character and a disulfide are catalytically significant groups of CO2-reductase from C. pasteurianum."}
{"id": "PMID:241690", "title": "Molecular biology of copper. A circular dichroism study on copper complexes of thionein and penicillamine.", "content": "Chicken liver Cd, Zn-thionein (metallothionein) was isolated from Cd-pretreated chickens weighing 1 500 g. The native Cd, Zn-thionein contained 9 g-atoms of metals per 12 000 g of protein. Upon the addition of Cu(CH3CN)4ClO4, all Cd2 and Zn2 were successfully replaced. 15 g-atoms of Cu from the acetonitrile perchlorate complex were bound to the protein. Due to the absence of aromatic amino acid residues, thionein has unique ultraviolet and circular dichroism properties. The shoulder of the ultraviolet spectrum at 250 nm (A250 X A280(-1) = 23.9) was shifted to 275 nm (A250 X A280(-1) = 1.6). No significant absorption was detected in the visible region. Th conformational changes of the protein moiety were much more visible in the circular dichroism spectra. The titration with Cu(CH3CH)2 caused the appearence of three new Cotton effects: 257.5 nm (+), 350 nm (+) and 301 nm (-). The negative Cotton effect at 239 nm of the original metallothionein was completely levelled off. The binding strength of copper with thionein is extraordinarily high: it survives proton treatment up to pH 1.9. Displacement of the Cd2 by Cu employing Cd-thionein which was formed at pH 2.2 resulted in the same circular dichroism properties as observed for Cu-thionein. D-Penicillamine proved a suitable model for the metal-free thionein, since redox reactions and polymerization of the sterically hindered thiol residue are known to be slow. The correlation of the circular dichroism properties of either copper complex using thionein or D-penicillamine was surprisingly high. Circular dichroism measurements of Cu(I)-D-penicillamine revealed Cotton effects at 255 nm (+), 280 nm (+) and 355 nm (-). Upon examining the red-violet mixed Cu(-i)-cu(II)-D-penicillamine complex, Cotton bands in the visible region at 425 nm (-) and 495 nm (+) were seen. In many blue copper enzymes, the copper is assumed to be in the neighborhood of both cysteine and aromatic amino acid residues, which are known to play an important role in the electron transfer. This is not the case in the Cu-thionein, which would explain many different properties of this copper protein. It is very attractive to conclude that the sterically hindered SH-group of D-penicillamine reacts with excess copper in a specific way, similar to the Cu-thionein. This phenomenon could explain the considerable success of D-penicillamine in the treatment of Wilson's disease.", "contents": "Molecular biology of copper. A circular dichroism study on copper complexes of thionein and penicillamine. Chicken liver Cd, Zn-thionein (metallothionein) was isolated from Cd-pretreated chickens weighing 1 500 g. The native Cd, Zn-thionein contained 9 g-atoms of metals per 12 000 g of protein. Upon the addition of Cu(CH3CN)4ClO4, all Cd2 and Zn2 were successfully replaced. 15 g-atoms of Cu from the acetonitrile perchlorate complex were bound to the protein. Due to the absence of aromatic amino acid residues, thionein has unique ultraviolet and circular dichroism properties. The shoulder of the ultraviolet spectrum at 250 nm (A250 X A280(-1) = 23.9) was shifted to 275 nm (A250 X A280(-1) = 1.6). No significant absorption was detected in the visible region. Th conformational changes of the protein moiety were much more visible in the circular dichroism spectra. The titration with Cu(CH3CH)2 caused the appearence of three new Cotton effects: 257.5 nm (+), 350 nm (+) and 301 nm (-). The negative Cotton effect at 239 nm of the original metallothionein was completely levelled off. The binding strength of copper with thionein is extraordinarily high: it survives proton treatment up to pH 1.9. Displacement of the Cd2 by Cu employing Cd-thionein which was formed at pH 2.2 resulted in the same circular dichroism properties as observed for Cu-thionein. D-Penicillamine proved a suitable model for the metal-free thionein, since redox reactions and polymerization of the sterically hindered thiol residue are known to be slow. The correlation of the circular dichroism properties of either copper complex using thionein or D-penicillamine was surprisingly high. Circular dichroism measurements of Cu(I)-D-penicillamine revealed Cotton effects at 255 nm (+), 280 nm (+) and 355 nm (-). Upon examining the red-violet mixed Cu(-i)-cu(II)-D-penicillamine complex, Cotton bands in the visible region at 425 nm (-) and 495 nm (+) were seen. In many blue copper enzymes, the copper is assumed to be in the neighborhood of both cysteine and aromatic amino acid residues, which are known to play an important role in the electron transfer. This is not the case in the Cu-thionein, which would explain many different properties of this copper protein. It is very attractive to conclude that the sterically hindered SH-group of D-penicillamine reacts with excess copper in a specific way, similar to the Cu-thionein. This phenomenon could explain the considerable success of D-penicillamine in the treatment of Wilson's disease."}
{"id": "PMID:241691", "title": "[15-Hydroxyprostaglandin dehydrogenase from human placenta. 1. Isolation and characterization].", "content": "15-Hydroxyprostaglandin dehydrogenase was isolated from human term placenta up to a final purification of 380-fold. A spec. act. of 2000 mU/mg of protein was reached. The preparation was not homogeneous as judged by analytical disc electrophoresis. The enzyme could be stored in the presence of 50% glycerol and 10mM 2-mercaptoethanol without any loss of activity for at least one year. A distinct single protein band stained after discontinuous polyacrylamide gel electrophoresis was shown by enzymatic activity staining to correspond to 15-hydroxyprostaglandin dehydrogenase activity. Thus no evidence for the exitstence of isoenzymes was obtained. The protein in the final preparation steps showed neither alcohol dehydrogenase, NAD reductase, nor NADH oxidase activity, nor enzymatic conversion of prostaglandin or 15-oxoprostaglandin in the absence of NAD and NADH. No spontaneous reactions between NAD and prostaglandin or NADH and 15-oxoprostaglandin were detectable in the absence of the enzyme. Ethanol and glycerol slightly inhibited the reaction. Various buffers (Tris/HC1, potassium phosphate, HEPES, and triethanolamine) and salts (ammonium chloride, ammonium sulfate, potassium chloride, and sodium chloride) had different effects on the reaction rate. The pH profile of the reaction shows a plateau between pH 7.0 and 7.8 and a steep maximum at pH 9.5. A linear Arrhenius plot was obtained for the temperature dependence of the reaction from 20 to 37 degrees C. The molar activation enthalpy of the reaction was calculated to be 13.1 kcal/mole. The molecular weight of 15-hydroxyprostaglandin dehydrogenase was estimated to be 32000 -/+ 3000 by gel filtration on Sephadex G-150 in the presence of 10mM mercaptoethanol.", "contents": "[15-Hydroxyprostaglandin dehydrogenase from human placenta. 1. Isolation and characterization]. 15-Hydroxyprostaglandin dehydrogenase was isolated from human term placenta up to a final purification of 380-fold. A spec. act. of 2000 mU/mg of protein was reached. The preparation was not homogeneous as judged by analytical disc electrophoresis. The enzyme could be stored in the presence of 50% glycerol and 10mM 2-mercaptoethanol without any loss of activity for at least one year. A distinct single protein band stained after discontinuous polyacrylamide gel electrophoresis was shown by enzymatic activity staining to correspond to 15-hydroxyprostaglandin dehydrogenase activity. Thus no evidence for the exitstence of isoenzymes was obtained. The protein in the final preparation steps showed neither alcohol dehydrogenase, NAD reductase, nor NADH oxidase activity, nor enzymatic conversion of prostaglandin or 15-oxoprostaglandin in the absence of NAD and NADH. No spontaneous reactions between NAD and prostaglandin or NADH and 15-oxoprostaglandin were detectable in the absence of the enzyme. Ethanol and glycerol slightly inhibited the reaction. Various buffers (Tris/HC1, potassium phosphate, HEPES, and triethanolamine) and salts (ammonium chloride, ammonium sulfate, potassium chloride, and sodium chloride) had different effects on the reaction rate. The pH profile of the reaction shows a plateau between pH 7.0 and 7.8 and a steep maximum at pH 9.5. A linear Arrhenius plot was obtained for the temperature dependence of the reaction from 20 to 37 degrees C. The molar activation enthalpy of the reaction was calculated to be 13.1 kcal/mole. The molecular weight of 15-hydroxyprostaglandin dehydrogenase was estimated to be 32000 -/+ 3000 by gel filtration on Sephadex G-150 in the presence of 10mM mercaptoethanol."}
{"id": "PMID:241692", "title": "[IMP-cyclohydrolase/transformylase from ehrlich-ascites carcinoma (author's transl)].", "content": "The IMP-cyclohydrolase/transformylase enzyme was purified from Ehrlich ascites tumor cells by ammonium sulfate fractionation and chromatography on Sephadex G-75 and DEAE-Sephadex. The electrophoretically pure enzyme has a molecular weight of about 350000, estimated by a gel filtration, and an isoelectric point of 6.2. It is composed of 8 subunits with a molecular weight of 46000. Every subunit is composed of two different proteins with a molecular weight of 18000 and 28500. Some further characteristics of the enzyme are reported.", "contents": "[IMP-cyclohydrolase/transformylase from ehrlich-ascites carcinoma (author's transl)]. The IMP-cyclohydrolase/transformylase enzyme was purified from Ehrlich ascites tumor cells by ammonium sulfate fractionation and chromatography on Sephadex G-75 and DEAE-Sephadex. The electrophoretically pure enzyme has a molecular weight of about 350000, estimated by a gel filtration, and an isoelectric point of 6.2. It is composed of 8 subunits with a molecular weight of 46000. Every subunit is composed of two different proteins with a molecular weight of 18000 and 28500. Some further characteristics of the enzyme are reported."}
{"id": "PMID:241693", "title": "Criteria of viability of isolated liver cells.", "content": "36.4 +/Various cellular parameters were measured with regard to their usefulness as criteria of viability of isolated cells. Stainability by trypan blue and release of lactate dehydrogenase indicate only severe irreversible damage of cells. Neither endogenous respiration nor even the ATP/ADP ratio is a sensitive criterion of viability. On aging of cells, the ATP/ADP ratio remains high, even though the membrane potential, the intracellular K concentration and the content of adenine nucleotides decrease considerably. A sensitive, easily performed test is the stimulation of cellular respiration by 1mM succinate. Only a damaged plasma membrane allows succinate permeation of a rate sufficient to stimulate respiration. The membrane potential and the intracellular Na and K concentrations are the most sensitive criteria of viability, since they indicate the earliest changes on aging. (For freshly isolated cells, we found a membrane potential of 36.4 \"/- 3.4 mv [n = 5], an intracellular K concentration of 109.0 +/- 9.1 mM, and an intracellular Na concentration of 47.0 +/- 13.4mM.) The incorporation of [14C]uridine also sensitively reflects cellular damage.", "contents": "Criteria of viability of isolated liver cells. 36.4 +/Various cellular parameters were measured with regard to their usefulness as criteria of viability of isolated cells. Stainability by trypan blue and release of lactate dehydrogenase indicate only severe irreversible damage of cells. Neither endogenous respiration nor even the ATP/ADP ratio is a sensitive criterion of viability. On aging of cells, the ATP/ADP ratio remains high, even though the membrane potential, the intracellular K concentration and the content of adenine nucleotides decrease considerably. A sensitive, easily performed test is the stimulation of cellular respiration by 1mM succinate. Only a damaged plasma membrane allows succinate permeation of a rate sufficient to stimulate respiration. The membrane potential and the intracellular Na and K concentrations are the most sensitive criteria of viability, since they indicate the earliest changes on aging. (For freshly isolated cells, we found a membrane potential of 36.4 \"/- 3.4 mv [n = 5], an intracellular K concentration of 109.0 +/- 9.1 mM, and an intracellular Na concentration of 47.0 +/- 13.4mM.) The incorporation of [14C]uridine also sensitively reflects cellular damage."}
{"id": "PMID:241694", "title": "Membrane effects on hepatic microsomal glucose-6-phosphatase.", "content": "1) Rat liver microsomes exhibit only a weak hydrolyzing activity towards galactose 6-phosphate. Disruption of the microsomal vesicles does not change the apparent Michaelis constant for this substrate but enhances the apparent maximum velocity. 2) The inhibition of microsomal glucose-6-phosphatase (EC 3.1.3.9) by galactose 6-phosphate is of the competitive type in intact and disrupted microsomal vesicles, suggesting that both substrates are hydrolyzed by the same enzyme. 3) The high degree of latency found for the hydrolysis of galactose 6-phosphate compared to glucose 6-phosphate indicates the presence of a carrier for glucose 6-phosphate in the microsomal membrane. 4) Since glucose as a product is not trapped inside the microsomal vesicles, this sugar probably is able to penetrate the microsomal membrane.", "contents": "Membrane effects on hepatic microsomal glucose-6-phosphatase. 1) Rat liver microsomes exhibit only a weak hydrolyzing activity towards galactose 6-phosphate. Disruption of the microsomal vesicles does not change the apparent Michaelis constant for this substrate but enhances the apparent maximum velocity. 2) The inhibition of microsomal glucose-6-phosphatase (EC 3.1.3.9) by galactose 6-phosphate is of the competitive type in intact and disrupted microsomal vesicles, suggesting that both substrates are hydrolyzed by the same enzyme. 3) The high degree of latency found for the hydrolysis of galactose 6-phosphate compared to glucose 6-phosphate indicates the presence of a carrier for glucose 6-phosphate in the microsomal membrane. 4) Since glucose as a product is not trapped inside the microsomal vesicles, this sugar probably is able to penetrate the microsomal membrane."}
{"id": "PMID:241695", "title": "A ligand-induced conformational change of yeast dipeptidase at physiological pH: kinetic consequences and possible regulatory significance.", "content": "The hydrolysis of dipeptides by purified yeast dipeptidase (EC 3.4.13.?) shows marked deviations from Michaelis-Menten kinetics over a wide range of pH. Quite anomalous kinetics is observed between pH 6 and 7, indicating a drastic change in the enzyme's properties. A reasonable explanation is provided by the assumption of a conformational transition brought about either by pH shifts or, at a constant pH, by changes in the substrate concentration. The transition, which may have a half-life on the order of minutes under appropriate conditions, is a distinctly cooperative process, with a dependence on ligand concentration higher than first order. The two forms of the enzyme differ clearly from each other with respect to various properties. The magnitudes and pH dependence of the kinetic parameters as well as the type of inhibition (or activation) exerted by amino acids and other ligands are different, as are their heat stabilities and the rates of inactivation by photooxidation of proteolytic  degradation. Neither the molecular weight nor the gross conformation of the enzyme changes during the transition, so it seems to be due to a local isomerization affecting mainly the geometry of the active site. The sensitivity of dipeptidase to changes in the concentrations of substrates and other ligands is most pronounced exactly at the values of pH known to prevail in the living yeast cell. Thus the observed effects, which modulate dipeptidase activities within wide and limits, according to the amounts of dipeptides and amino acids present, are likely to play a role in the regulation of the enzyme in vivo.", "contents": "A ligand-induced conformational change of yeast dipeptidase at physiological pH: kinetic consequences and possible regulatory significance. The hydrolysis of dipeptides by purified yeast dipeptidase (EC 3.4.13.?) shows marked deviations from Michaelis-Menten kinetics over a wide range of pH. Quite anomalous kinetics is observed between pH 6 and 7, indicating a drastic change in the enzyme's properties. A reasonable explanation is provided by the assumption of a conformational transition brought about either by pH shifts or, at a constant pH, by changes in the substrate concentration. The transition, which may have a half-life on the order of minutes under appropriate conditions, is a distinctly cooperative process, with a dependence on ligand concentration higher than first order. The two forms of the enzyme differ clearly from each other with respect to various properties. The magnitudes and pH dependence of the kinetic parameters as well as the type of inhibition (or activation) exerted by amino acids and other ligands are different, as are their heat stabilities and the rates of inactivation by photooxidation of proteolytic  degradation. Neither the molecular weight nor the gross conformation of the enzyme changes during the transition, so it seems to be due to a local isomerization affecting mainly the geometry of the active site. The sensitivity of dipeptidase to changes in the concentrations of substrates and other ligands is most pronounced exactly at the values of pH known to prevail in the living yeast cell. Thus the observed effects, which modulate dipeptidase activities within wide and limits, according to the amounts of dipeptides and amino acids present, are likely to play a role in the regulation of the enzyme in vivo."}
{"id": "PMID:241696", "title": "The pH-dependence of the peptidase activity of aminoacylase.", "content": "Aminoacylase is a potent peptidase around pH 8.5. The pH dependence of the Km values reveals that only dipeptides with uncharged N-terminal amino acids are substrates of the enzyme. The Km values reflect the hydrophobicity of the N-terminal amino acids. Calculated on the basis of unprotonated peptides they are pH independent. Hydrophobic, deprotonated amino acids are competitive inhibitors of the enzyme, tryptophan and norleucine being the strongest inhibitors. Inhibitor constants with glycylalanine as substrate have been determined for several amino acids. From the present results it may be deduced that the N-terminal amino acids of dipeptides are bound at a strongly hydrophobic site.", "contents": "The pH-dependence of the peptidase activity of aminoacylase. Aminoacylase is a potent peptidase around pH 8.5. The pH dependence of the Km values reveals that only dipeptides with uncharged N-terminal amino acids are substrates of the enzyme. The Km values reflect the hydrophobicity of the N-terminal amino acids. Calculated on the basis of unprotonated peptides they are pH independent. Hydrophobic, deprotonated amino acids are competitive inhibitors of the enzyme, tryptophan and norleucine being the strongest inhibitors. Inhibitor constants with glycylalanine as substrate have been determined for several amino acids. From the present results it may be deduced that the N-terminal amino acids of dipeptides are bound at a strongly hydrophobic site."}
{"id": "PMID:241697", "title": "Purification and properties of UDP-glucose galactosylhydroxylysine collagen glucosyltransferase (EC 2.4.1.?) from bovine arterial tissue.", "content": "The glucosyltransferase (UDP-glucose galactosylhydroxylsine collagen glucosyltransferase, EC 2.4.1.?.) was purified 50-fold from calf arterial tissue by ammonium sulfate precipitation, gel filtration and electrofocusing. The purified enzyme has a molecular weight of 72 000 and a requirement for Mn2. It resolves into two activity peaks when submitted to electrofocusing (isoelectric point at pH 4.2 and 8.1) or disc electrophoresis and exhibits a double pH optimum (pH 8.3 and 9.9). The enzyme was found to transfer glucose from UDP-glucose to the denatured forms of citrate-soluble calf skin collagen (I), the alphal chain (II) and the beta12 component (III) derived from it, and of an acetic-acid-souble collagen preparation (IV) obtained from alkali-treated calf arterial tissue. The Km values for the substrates were 1.67 X 10(-4) (I), 6.3 X 10(-4) (II), 3.3 X 10(-4) (III) and 2.8 X 10(-4) mol/l (IV), indicating that the enzyme has the greatest affinity for the calf skin collagen. The glucose transferred to hydroxylysine-linked galactose residues may be released subsequently by the action of a specific alpha-glucosidase purified from bovine spleen. The results support the assumtion that the glucosylation step in the course of the (pro-)-collagen biosynthesis depends on special structural features of the substrate and may be controlled by a specific alpha-glucosidase.", "contents": "Purification and properties of UDP-glucose galactosylhydroxylysine collagen glucosyltransferase (EC 2.4.1.?) from bovine arterial tissue. The glucosyltransferase (UDP-glucose galactosylhydroxylsine collagen glucosyltransferase, EC 2.4.1.?.) was purified 50-fold from calf arterial tissue by ammonium sulfate precipitation, gel filtration and electrofocusing. The purified enzyme has a molecular weight of 72 000 and a requirement for Mn2. It resolves into two activity peaks when submitted to electrofocusing (isoelectric point at pH 4.2 and 8.1) or disc electrophoresis and exhibits a double pH optimum (pH 8.3 and 9.9). The enzyme was found to transfer glucose from UDP-glucose to the denatured forms of citrate-soluble calf skin collagen (I), the alphal chain (II) and the beta12 component (III) derived from it, and of an acetic-acid-souble collagen preparation (IV) obtained from alkali-treated calf arterial tissue. The Km values for the substrates were 1.67 X 10(-4) (I), 6.3 X 10(-4) (II), 3.3 X 10(-4) (III) and 2.8 X 10(-4) mol/l (IV), indicating that the enzyme has the greatest affinity for the calf skin collagen. The glucose transferred to hydroxylysine-linked galactose residues may be released subsequently by the action of a specific alpha-glucosidase purified from bovine spleen. The results support the assumtion that the glucosylation step in the course of the (pro-)-collagen biosynthesis depends on special structural features of the substrate and may be controlled by a specific alpha-glucosidase."}
{"id": "PMID:241698", "title": "Evidence for different glycohydrolase and glycosyltransferase activities of beta-N-acetylglucosaminidases A and B.", "content": "1) Two forms of beta-N-acetylglucosaminidase--known as form A and form B - were purified from bovine spleen homogenates and efficaciously separated by preparative disc electrophoresis on polyacrylamide gel. Studies on the enzymatic specificity revealed that the two forms have different glycoside hydrolase and glycosyl transferase activities towards substrates of natural origin. 2) With the trisaccharide GlcNAc-GlcUA-GlcNAc from hyaluronate as substrate, form A released free N-acetylglucosamine at a rate 35-40 times higher than form B. The B form, however, transferred N-acetyl-[6-3H]glucosamine from phenyl-beta-N-acetyl-D[6-3H]glucosaminide to the tetrasaccharides GlcUA-GalNAc-4-sulfate-GlcUA--GalNAc-4-sulfate or GlcUA-GlcNAc-GlcUA-GlcNAc isolated from chondroitin 4-sulfate or hyaluronate at rates 5-10 times higher than beta-N-acetyl-glucosaminidase A, the corresponding 3H-pentasaccharides being isolated as reaction products. 3) The pH optimum of the glycoside hydrolase activity is 4.5, while optimum glycosyl transfer proceeds at pH 6.5. Under condition optimum for glycoside transferase, hydrolytic activity is still observed with each form, but the B form exhibits about equal glycoside hydrolase and glycoside transferase activity, whereas the A form has a predominant glycoside hydrolase action.", "contents": "Evidence for different glycohydrolase and glycosyltransferase activities of beta-N-acetylglucosaminidases A and B. 1) Two forms of beta-N-acetylglucosaminidase--known as form A and form B - were purified from bovine spleen homogenates and efficaciously separated by preparative disc electrophoresis on polyacrylamide gel. Studies on the enzymatic specificity revealed that the two forms have different glycoside hydrolase and glycosyl transferase activities towards substrates of natural origin. 2) With the trisaccharide GlcNAc-GlcUA-GlcNAc from hyaluronate as substrate, form A released free N-acetylglucosamine at a rate 35-40 times higher than form B. The B form, however, transferred N-acetyl-[6-3H]glucosamine from phenyl-beta-N-acetyl-D[6-3H]glucosaminide to the tetrasaccharides GlcUA-GalNAc-4-sulfate-GlcUA--GalNAc-4-sulfate or GlcUA-GlcNAc-GlcUA-GlcNAc isolated from chondroitin 4-sulfate or hyaluronate at rates 5-10 times higher than beta-N-acetyl-glucosaminidase A, the corresponding 3H-pentasaccharides being isolated as reaction products. 3) The pH optimum of the glycoside hydrolase activity is 4.5, while optimum glycosyl transfer proceeds at pH 6.5. Under condition optimum for glycoside transferase, hydrolytic activity is still observed with each form, but the B form exhibits about equal glycoside hydrolase and glycoside transferase activity, whereas the A form has a predominant glycoside hydrolase action."}
{"id": "PMID:241700", "title": "Gd(--) Abrami: a deficient G-6PD variant with hemizygous expression in blood cells of a woman with primary myelofibrosis.", "content": "A new deficient G-6PD variant, Gd(--) Abrami, was found in granulocytes, platelets and red blood cells of a 65-year-old woman with myelofibrosis. Enzyme and immunological titrations showed that only the deficient variant was present in blood cells whereas both the normal and abnormal enzymes were found in the fat cells of this patient. These results seem to indicate that the granulocytes, platelets and erythrocytes of this woman with myelofibrosis have arisen from a single abnormal precursor the functional X chromosome of which is the one carrying the abnormal G-6PD gene.", "contents": "Gd(--) Abrami: a deficient G-6PD variant with hemizygous expression in blood cells of a woman with primary myelofibrosis. A new deficient G-6PD variant, Gd(--) Abrami, was found in granulocytes, platelets and red blood cells of a 65-year-old woman with myelofibrosis. Enzyme and immunological titrations showed that only the deficient variant was present in blood cells whereas both the normal and abnormal enzymes were found in the fat cells of this patient. These results seem to indicate that the granulocytes, platelets and erythrocytes of this woman with myelofibrosis have arisen from a single abnormal precursor the functional X chromosome of which is the one carrying the abnormal G-6PD gene."}
{"id": "PMID:241701", "title": "Comparative studies on the human glutamate-pyruvate transaminase phenotypes--GPT 1, GPT 2-1, GPT 2.", "content": "The quantitative differences between the activity of the 3 common phenotypes of human red cell GPT has been confirmed. In addition, the activity of red cell GPT 1 was found to be greater in young children than in adults. No such difference was found for the GPT 2 phenotype. The activity of the red cell GPT 1 was found to decrease with age, reaching the adult level at the age of 10 to 12 years. Red cell GPT of all the 3 common phenotypes in both adults and children was found to show a similar response to the addition of excess pyridoxal phosphate. A method has been devised for the partial purification of human GPT (cytoplasmic) from liver. GPT 1 and GPT 2 have been purified, and very few significant differences were found amongst the physical and kinetic parameters tested.", "contents": "Comparative studies on the human glutamate-pyruvate transaminase phenotypes--GPT 1, GPT 2-1, GPT 2. The quantitative differences between the activity of the 3 common phenotypes of human red cell GPT has been confirmed. In addition, the activity of red cell GPT 1 was found to be greater in young children than in adults. No such difference was found for the GPT 2 phenotype. The activity of the red cell GPT 1 was found to decrease with age, reaching the adult level at the age of 10 to 12 years. Red cell GPT of all the 3 common phenotypes in both adults and children was found to show a similar response to the addition of excess pyridoxal phosphate. A method has been devised for the partial purification of human GPT (cytoplasmic) from liver. GPT 1 and GPT 2 have been purified, and very few significant differences were found amongst the physical and kinetic parameters tested."}
{"id": "PMID:241719", "title": "[Virus infections of the respiratory tract in childhood (author's transl)].", "content": "Comprehensive epidemiological studies revealed that every individual is suffering from a respiratory tract infection in the average 6 times a year. 97% of these are caused by viruses. Identical clinical symptoms may be produced by many different agents, thus the etiology of an illness can only be identified by virus isolation and serological tests. The frequency of isolations is varying in adults and in children as well as in ambulatory and in hospitalized patients. The persistently observed susceptibility for new infections is caused by the great variety of possible etiologic agents especially in upper respiratory infections and the peculiarities of local immunity in the respiratory tract. An influence of chilling could not be demonstrated scientifically in spite of controverse clinical observations. It was proved however that allergic individuals succumb more frequently to viral infections. Overweight in infancy increases susceptibility for bronchitis and bronchiolitis. Superinfections by bacteriae are not rarely complications of viral diseases and antibiotic therapy may become necessary eventually. Leucocytosis and an elevated erythrocyte sedimentation rate are only criteria of limited value to distinguish viral and bacterial infections. Specific virostatic therapy is not possible so far for respiratory tract illnesses, but for prophylaxis of infections with influenza A2 amantadine-HCl may be used. Gammaglobulin has a prophylactic effect as well for certain virus infections but is of little use for antiviral therapy.", "contents": "[Virus infections of the respiratory tract in childhood (author's transl)]. Comprehensive epidemiological studies revealed that every individual is suffering from a respiratory tract infection in the average 6 times a year. 97% of these are caused by viruses. Identical clinical symptoms may be produced by many different agents, thus the etiology of an illness can only be identified by virus isolation and serological tests. The frequency of isolations is varying in adults and in children as well as in ambulatory and in hospitalized patients. The persistently observed susceptibility for new infections is caused by the great variety of possible etiologic agents especially in upper respiratory infections and the peculiarities of local immunity in the respiratory tract. An influence of chilling could not be demonstrated scientifically in spite of controverse clinical observations. It was proved however that allergic individuals succumb more frequently to viral infections. Overweight in infancy increases susceptibility for bronchitis and bronchiolitis. Superinfections by bacteriae are not rarely complications of viral diseases and antibiotic therapy may become necessary eventually. Leucocytosis and an elevated erythrocyte sedimentation rate are only criteria of limited value to distinguish viral and bacterial infections. Specific virostatic therapy is not possible so far for respiratory tract illnesses, but for prophylaxis of infections with influenza A2 amantadine-HCl may be used. Gammaglobulin has a prophylactic effect as well for certain virus infections but is of little use for antiviral therapy."}
{"id": "PMID:241720", "title": "Chicken (Gallus gallus) hemolytic complement: optimal conditions for its titration.", "content": "The effect of pH, ionic strength, cation concentration, ethylenediaminetetraacetic acid trisodium salt (Na3EDTA), time and temperature were studied to determine the optimal conditions for titrating the hemolytic complement (C) activity in sera of chicken (Gallus gallus). Swine erythrocytes (E) sensitized with rabbit antibodies were the most sensitive, while chicken serum had a smaller amount of \"natural\" antibody against them than against red blood cells from other five species tested. The highest titers of chicken C, when tested with swine sensitized E, were detected when isotonic NaCl-barbital buffer was used as diluent, having the ionic strength of 0.15, conductance of 11 millimhos/cm at 20 degrees C. However, maximal chicken C titers detected with sensitized rabbit E were obtained at ionic strength of 0.07 to 0.11 depending on pH. A final concentration of 1 X 10(-3) M of Mg2+ and 3 X 10(-4) M of Ca2+ and pH 8 were optimal in both cases. The temperature of 30 degrees C and time of 60 minutes were appropriate to reveal the maximal titers..", "contents": "Chicken (Gallus gallus) hemolytic complement: optimal conditions for its titration. The effect of pH, ionic strength, cation concentration, ethylenediaminetetraacetic acid trisodium salt (Na3EDTA), time and temperature were studied to determine the optimal conditions for titrating the hemolytic complement (C) activity in sera of chicken (Gallus gallus). Swine erythrocytes (E) sensitized with rabbit antibodies were the most sensitive, while chicken serum had a smaller amount of \"natural\" antibody against them than against red blood cells from other five species tested. The highest titers of chicken C, when tested with swine sensitized E, were detected when isotonic NaCl-barbital buffer was used as diluent, having the ionic strength of 0.15, conductance of 11 millimhos/cm at 20 degrees C. However, maximal chicken C titers detected with sensitized rabbit E were obtained at ionic strength of 0.07 to 0.11 depending on pH. A final concentration of 1 X 10(-3) M of Mg2+ and 3 X 10(-4) M of Ca2+ and pH 8 were optimal in both cases. The temperature of 30 degrees C and time of 60 minutes were appropriate to reveal the maximal titers.."}
{"id": "PMID:241721", "title": "Purification of soluble complement-fixing antigens from two Burkitt's lymphoma cell lines. Conditions affecting the stability and recovery of antigens and antibodies.", "content": "Soluble Epstein--Barr virus (EBV) associated antigens of P3HR-1 and Raji cell lines, which fix complement in the presence of human sera containing antibody against EBV--VCA antigens, were partially purified by fractionating centrifuged cell lysates by the method of immunoadsorbents or by precipitation with ammonium sulphate or glycine--HCl. Purification conditions were limited by the instability of both antigen and antibody activity. The antibody was inactivated under all the conditions commonly used to dissociate antigen--antibody complexes. The antigen was inactivated at pH 2-3, and was irreversibly bound to Sephadex G-200 conjugates which had not been exposed to large excesses of serum.", "contents": "Purification of soluble complement-fixing antigens from two Burkitt's lymphoma cell lines. Conditions affecting the stability and recovery of antigens and antibodies. Soluble Epstein--Barr virus (EBV) associated antigens of P3HR-1 and Raji cell lines, which fix complement in the presence of human sera containing antibody against EBV--VCA antigens, were partially purified by fractionating centrifuged cell lysates by the method of immunoadsorbents or by precipitation with ammonium sulphate or glycine--HCl. Purification conditions were limited by the instability of both antigen and antibody activity. The antibody was inactivated under all the conditions commonly used to dissociate antigen--antibody complexes. The antigen was inactivated at pH 2-3, and was irreversibly bound to Sephadex G-200 conjugates which had not been exposed to large excesses of serum."}
{"id": "PMID:241722", "title": "[Changes in the acid-base equilibrium in hypokalemic patients during potassium infusions with various anions].", "content": "Based on the parameters of the acid-base status, the effect of different anions in potassium and magnesium substitution was studied. A mixture of chloride with the metabolisable anions acetate and malate does not cause any changes in the acid-base balance. The exclusive supply of metabolisable anions in the form of aspartate always results in a change of blood pH values towards an alkalosis.", "contents": "[Changes in the acid-base equilibrium in hypokalemic patients during potassium infusions with various anions]. Based on the parameters of the acid-base status, the effect of different anions in potassium and magnesium substitution was studied. A mixture of chloride with the metabolisable anions acetate and malate does not cause any changes in the acid-base balance. The exclusive supply of metabolisable anions in the form of aspartate always results in a change of blood pH values towards an alkalosis."}
{"id": "PMID:241723", "title": "[Acid-base equilibrium- -disorders and therapy].", "content": "The purpose of this work is to give a brief resume, with figures and tables, of the knowledge concerning the acid-base balance which is indispensable in intensive therapy. The effects of disturbances of the acid-base balance on organic functions are shown and, therefore, the importance of a situation-adapted therapy is particularly stressed. In this connection, the role of infusion therapy in the treatment of disturbances of the acid-base balance is especially discussed.", "contents": "[Acid-base equilibrium- -disorders and therapy]. The purpose of this work is to give a brief resume, with figures and tables, of the knowledge concerning the acid-base balance which is indispensable in intensive therapy. The effects of disturbances of the acid-base balance on organic functions are shown and, therefore, the importance of a situation-adapted therapy is particularly stressed. In this connection, the role of infusion therapy in the treatment of disturbances of the acid-base balance is especially discussed."}
{"id": "PMID:241724", "title": "[Systematic and random errors in the determination of parameters of the acid-base equilibrium].", "content": "A review is given of the most common errors made in the estimation of the parameters of acid-base balance. Especially important are the systematic errors, for instance in handling the blood before estimation, by use of incorrect standard solutions or poor temperature control during the measurement of the pH. By paying attention to these details, it is possible to obtain excellent precision in final measurement in the standard apparatus.", "contents": "[Systematic and random errors in the determination of parameters of the acid-base equilibrium]. A review is given of the most common errors made in the estimation of the parameters of acid-base balance. Especially important are the systematic errors, for instance in handling the blood before estimation, by use of incorrect standard solutions or poor temperature control during the measurement of the pH. By paying attention to these details, it is possible to obtain excellent precision in final measurement in the standard apparatus."}
{"id": "PMID:241725", "title": "Barriers to the nurse practitioner movement: problems of women in a woman's field.", "content": "Barriers to the nurse practitioner movement are explored in this article. Historically, the subordination of women and the sex segregation of nursing and medicine have helped to establish interaction patterns between the two professions which included a subordination of nurses as well as informal doctor-nurse games. These patterns were reinforced by hospital training schools and state laws which restricted the roles of nurses. Recent changes in state movement, but the stereotyped communication patterns between nurses and physicians remain as a barrier to the full use of the talents of nurses in practitioner roles.", "contents": "Barriers to the nurse practitioner movement: problems of women in a woman's field. Barriers to the nurse practitioner movement are explored in this article. Historically, the subordination of women and the sex segregation of nursing and medicine have helped to establish interaction patterns between the two professions which included a subordination of nurses as well as informal doctor-nurse games. These patterns were reinforced by hospital training schools and state laws which restricted the roles of nurses. Recent changes in state movement, but the stereotyped communication patterns between nurses and physicians remain as a barrier to the full use of the talents of nurses in practitioner roles."}
{"id": "PMID:241727", "title": "The methylsulfonylethyloxycarbonyl group, a new and versatile amino protective function.", "content": "A new amino protecting group, the methylsulfonylethyloxycarbonyl (Msc) group, is described which combines well with other familiar groups (benzyloxycarbonyl, t-butyloxycarbonyl) in peptide syntheses. Its main characteristics are an extreme acid stability, a high base lability and a high polarity which enhances solubility in polar solvents including water. The group resists catalytic hydrogenolysis but does not poison the catalyst. It has good crystallizing properties. Application in peptide synthesis is exemplified in the synthesis of Msc-Phe-Arg-Trp-Gly-OMe.HCl. Deprotection of the masked tetrapeptide was accomplished within 5 sec with a 1.0 N solution of base (OH- and OCH3-). A reaction scheme for the cleavage of the group is suggested.", "contents": "The methylsulfonylethyloxycarbonyl group, a new and versatile amino protective function. A new amino protecting group, the methylsulfonylethyloxycarbonyl (Msc) group, is described which combines well with other familiar groups (benzyloxycarbonyl, t-butyloxycarbonyl) in peptide syntheses. Its main characteristics are an extreme acid stability, a high base lability and a high polarity which enhances solubility in polar solvents including water. The group resists catalytic hydrogenolysis but does not poison the catalyst. It has good crystallizing properties. Application in peptide synthesis is exemplified in the synthesis of Msc-Phe-Arg-Trp-Gly-OMe.HCl. Deprotection of the masked tetrapeptide was accomplished within 5 sec with a 1.0 N solution of base (OH- and OCH3-). A reaction scheme for the cleavage of the group is suggested."}
{"id": "PMID:241728", "title": "Radiation inactivation of rabbit muscle aldolase.", "content": "Pulse radiolysis and steady-state X-radiolysis have been used to investigate the radiation inactivation of aldolase from rabbit muscle. Both eaq-and OH readily react with aldolase, and contribute to inactivation. The radical anions (CNS)2-and (Br)2-react with aldolase at neutral pH. The progressive addition of alkali results in an increase in the second-order rate constants, with an apparent pK approximately 10 +/- 0-3, and with the formation of an unstable intermediate, lambdamax approximately 400 nm resembling a phenoxyl radical. Steady-state radiolysis in the presence of (CNS)2-and (Br)2- at alkaline pH results in increased aldolase inactivation, with a pK of enzyme inactivation similar to that observed for reaction of the radical anions. We propose that a reaction of the radical anoins with tyrosine residues accounts for the resultant inactivation.", "contents": "Radiation inactivation of rabbit muscle aldolase. Pulse radiolysis and steady-state X-radiolysis have been used to investigate the radiation inactivation of aldolase from rabbit muscle. Both eaq-and OH readily react with aldolase, and contribute to inactivation. The radical anions (CNS)2-and (Br)2-react with aldolase at neutral pH. The progressive addition of alkali results in an increase in the second-order rate constants, with an apparent pK approximately 10 +/- 0-3, and with the formation of an unstable intermediate, lambdamax approximately 400 nm resembling a phenoxyl radical. Steady-state radiolysis in the presence of (CNS)2-and (Br)2- at alkaline pH results in increased aldolase inactivation, with a pK of enzyme inactivation similar to that observed for reaction of the radical anions. We propose that a reaction of the radical anoins with tyrosine residues accounts for the resultant inactivation."}
{"id": "PMID:241729", "title": "Folic acid conjugase from plasma. III. Use of the enzyme in the estimation of folate activity in foods.", "content": "A convenient method for the estimation of food folates using human plasma as a source of folic acid conjugase has been standardized. Bovine, goat and dog plasma could not be used for the purpose because of low enzyme activity and slow reaction rates. Human plasma conjugase released food folates from conjugated forms over a pH range of 4.5 to 6.0. The food folate values obtained by employing rat liver and chicken pancreas conjugase closely agreed with the values obtained by using human plasma conjugase. The advantages in using human plasma as a source of conjugase were (1) easy availability (2) non-essentiality of preliminary processing (3) stability of the enzyme on storing plasma in cold (4) low enzyme blank folate activity and (5) low amount of plasma needed for assay. Using this method, folic acid activity of some common Indian foods of plant and animal origin has been estimated. There were wide variations in the folate activity of different classes of foods. In general legumes and green leafy vegetables were found to be rich in folate activity.", "contents": "Folic acid conjugase from plasma. III. Use of the enzyme in the estimation of folate activity in foods. A convenient method for the estimation of food folates using human plasma as a source of folic acid conjugase has been standardized. Bovine, goat and dog plasma could not be used for the purpose because of low enzyme activity and slow reaction rates. Human plasma conjugase released food folates from conjugated forms over a pH range of 4.5 to 6.0. The food folate values obtained by employing rat liver and chicken pancreas conjugase closely agreed with the values obtained by using human plasma conjugase. The advantages in using human plasma as a source of conjugase were (1) easy availability (2) non-essentiality of preliminary processing (3) stability of the enzyme on storing plasma in cold (4) low enzyme blank folate activity and (5) low amount of plasma needed for assay. Using this method, folic acid activity of some common Indian foods of plant and animal origin has been estimated. There were wide variations in the folate activity of different classes of foods. In general legumes and green leafy vegetables were found to be rich in folate activity."}
{"id": "PMID:241730", "title": "Standardized aerobic and anaerobic exercise: differential effects on intraocular tension, blood pH, and lactate.", "content": "The effects of standardized aerobic and anaerobic exercise intensities on intraocular tension, blood lactate, and pH were studied. Intraocular tension decreased rapidly at all exercise intensities. The absolute lowest level of intraocular tension reached with aerobic and anaerobic exercise levels varied by only 1.5 mm. Hg and this difference was not statistically significant. Blood lactate and pH changes correlated with intraocular tension changes at anaerobic exercise levels, but not at aerobic exercise levels. These findings associated with aerobic exercise have not been previously reported. It is suggested that parameters other than the decrease in blood pH and the increase in blood lactate are responsible for most of the decrease in intraocular tension associated with dynamic exercise.", "contents": "Standardized aerobic and anaerobic exercise: differential effects on intraocular tension, blood pH, and lactate. The effects of standardized aerobic and anaerobic exercise intensities on intraocular tension, blood lactate, and pH were studied. Intraocular tension decreased rapidly at all exercise intensities. The absolute lowest level of intraocular tension reached with aerobic and anaerobic exercise levels varied by only 1.5 mm. Hg and this difference was not statistically significant. Blood lactate and pH changes correlated with intraocular tension changes at anaerobic exercise levels, but not at aerobic exercise levels. These findings associated with aerobic exercise have not been previously reported. It is suggested that parameters other than the decrease in blood pH and the increase in blood lactate are responsible for most of the decrease in intraocular tension associated with dynamic exercise."}
{"id": "PMID:241731", "title": "Reversal of oliguria and renal cortical ischemia of hemorrhagic shock in the dog with tris (hydroxymethyl) amino methane (THAM). Hemodynamic studies.", "content": "We investigated the functional and hemodynamic effects on the kidney of tris (hydroxymethyl) amino methane (THAM) infusion during sustained hemorrhagic hypotension in dogs. The large osmotic load introduced into the vascular compartment during hemorrhagic hypotension resulted in a marked reduction in systemic vascular resistance and a return of cardiac output, total renal blood flow, and the renal arteriographic pattern to normal range. The observed diuresis is probably due to an osmotic effect, because the glomerular filtration rate remains significantly depressed. Anatomical assignment of the mathematical components of the xenon washout curve led to an assessment of intrarenal blood flow distribution that was at variance with the arteriographic pattern and the intrarenal distribution of tagged microspheres.", "contents": "Reversal of oliguria and renal cortical ischemia of hemorrhagic shock in the dog with tris (hydroxymethyl) amino methane (THAM). Hemodynamic studies. We investigated the functional and hemodynamic effects on the kidney of tris (hydroxymethyl) amino methane (THAM) infusion during sustained hemorrhagic hypotension in dogs. The large osmotic load introduced into the vascular compartment during hemorrhagic hypotension resulted in a marked reduction in systemic vascular resistance and a return of cardiac output, total renal blood flow, and the renal arteriographic pattern to normal range. The observed diuresis is probably due to an osmotic effect, because the glomerular filtration rate remains significantly depressed. Anatomical assignment of the mathematical components of the xenon washout curve led to an assessment of intrarenal blood flow distribution that was at variance with the arteriographic pattern and the intrarenal distribution of tagged microspheres."}
{"id": "PMID:241735", "title": "The use of hexazonium-p-rosanilin in the histochemical demonstration of peptidases.", "content": "The suitability of hexazonium-p-rosanilin (HP) in the histochemical demonstration of peptidases was investigated. The detection was carried out in cold mictrotome sections adherent to slides or semipermeable membranes. Alanyl-1-naphthylamide, alanyl-2-naphthylamide, leucyl-2-naphthylamide, leucyl-4-methoxy-2-naphthylamide (all substrates in concentration of 0.4 mg/1 ml of citrate phosphate buffer pH 6.5), gamma-L-glutamyl-1-naphthylamide, gamma-L-glutamyl-2-naphthylamide (both substances in concentration of 0.24 mg/1 ml of acetate buffer pH 6.5) were used as the substrates. Results were compared with those obtained with Fast Blue B and Fast Garnet GBC. In comparison with Fast Blue B and Fast Garnet GBC HP is a faster coupler, furnishes azodyes which are stable, amorphous (even without lipid extractions from sections), more substantive and in the case of 1-naphthylamine almost insoluble in ordinary lipid solvents used for the dehydration and clearing of sections before mounting. The molecular extinction coefficient of azodyes furnished by HP is 1.5X higher for 1-naphthylamine than for 2-naphthylamine. It is higher than that of Fast Garnet GBC, however, lower than that of Fast Blue B. The inhibitory influence of individual diazonium salts on enzyme activity (activities) splitting leucyl-2-naphthylamide amounts to 36% (Fast Garnet GBC), 37% (Fast Blue B), 52% (HP, 0.03 ml/1 ml) and 63% (HP, 0.09 ml/1 ml) at pH 6.5. For gamma-glutamyl-transpeptidase the corresponding values are 50%, 59%, 62% and 67%. The higher inhibitory influence of HP is compensated by the possibility of its using in the technic of semipermeable membranes. HP improves greatly the localization of peptidases in cold microtome sections from which lipids were not extracted. The best results are furnished by 1-naphthylamine dervatives. In the case of 4-methoxy-2-naphthylamine derivatives the localization is very sharp, however, the azodye is less distinct than that of 2-naphthylamine. The localization as obtained with HP in combination with substrates derived of simple naphthylamines is similar or even better than with 4-methoxy-2-naphthylamine derivatives applied with Fast Blue B. Typical examples are shown.", "contents": "The use of hexazonium-p-rosanilin in the histochemical demonstration of peptidases. The suitability of hexazonium-p-rosanilin (HP) in the histochemical demonstration of peptidases was investigated. The detection was carried out in cold mictrotome sections adherent to slides or semipermeable membranes. Alanyl-1-naphthylamide, alanyl-2-naphthylamide, leucyl-2-naphthylamide, leucyl-4-methoxy-2-naphthylamide (all substrates in concentration of 0.4 mg/1 ml of citrate phosphate buffer pH 6.5), gamma-L-glutamyl-1-naphthylamide, gamma-L-glutamyl-2-naphthylamide (both substances in concentration of 0.24 mg/1 ml of acetate buffer pH 6.5) were used as the substrates. Results were compared with those obtained with Fast Blue B and Fast Garnet GBC. In comparison with Fast Blue B and Fast Garnet GBC HP is a faster coupler, furnishes azodyes which are stable, amorphous (even without lipid extractions from sections), more substantive and in the case of 1-naphthylamine almost insoluble in ordinary lipid solvents used for the dehydration and clearing of sections before mounting. The molecular extinction coefficient of azodyes furnished by HP is 1.5X higher for 1-naphthylamine than for 2-naphthylamine. It is higher than that of Fast Garnet GBC, however, lower than that of Fast Blue B. The inhibitory influence of individual diazonium salts on enzyme activity (activities) splitting leucyl-2-naphthylamide amounts to 36% (Fast Garnet GBC), 37% (Fast Blue B), 52% (HP, 0.03 ml/1 ml) and 63% (HP, 0.09 ml/1 ml) at pH 6.5. For gamma-glutamyl-transpeptidase the corresponding values are 50%, 59%, 62% and 67%. The higher inhibitory influence of HP is compensated by the possibility of its using in the technic of semipermeable membranes. HP improves greatly the localization of peptidases in cold microtome sections from which lipids were not extracted. The best results are furnished by 1-naphthylamine dervatives. In the case of 4-methoxy-2-naphthylamine derivatives the localization is very sharp, however, the azodye is less distinct than that of 2-naphthylamine. The localization as obtained with HP in combination with substrates derived of simple naphthylamines is similar or even better than with 4-methoxy-2-naphthylamine derivatives applied with Fast Blue B. Typical examples are shown."}
{"id": "PMID:241732", "title": "Contrast and electrolyte dynamics of the intravenous pyelogram. I. Urinary pH and volume changes in the canine I. V. P.", "content": "Canine peripheral venous or suprarenal aortic injections of sodium or meglumine iothalamate produced a significant swing towards an alkaline urine only in individual dogs injected with meglumine salts. When mean values were compared for the sodium or meglumine groups as a whole, however, no significant differences could be established for pH change or induced diuresis. With both salts, ATPase inhibition could play a role in urinary electrolyte excretion. Carbonic anhydrase inhibition does not seem to play a significant role in urinary pH changes induced by contrast media.", "contents": "Contrast and electrolyte dynamics of the intravenous pyelogram. I. Urinary pH and volume changes in the canine I. V. P. Canine peripheral venous or suprarenal aortic injections of sodium or meglumine iothalamate produced a significant swing towards an alkaline urine only in individual dogs injected with meglumine salts. When mean values were compared for the sodium or meglumine groups as a whole, however, no significant differences could be established for pH change or induced diuresis. With both salts, ATPase inhibition could play a role in urinary electrolyte excretion. Carbonic anhydrase inhibition does not seem to play a significant role in urinary pH changes induced by contrast media."}
{"id": "PMID:241736", "title": "The UV fading of hydrocarbon fluorescence and its prevention for observations in single living cells.", "content": "Excitation intensities used for standard microspectrofluorometric observations of natural cell fluorescence, i.e. NAD(P)H, lead to fading of hydrocarbon (polycyclic aromatic, heterocyclic) fluorescence in EL2 cells incubated with such compounds. The disappearance of hydrocarbon fluorescence under excitation at 366 nm seems to be an exponential function of time. The fading prevents studies on hydrocarbon metabolization in correlation with intracellular microelectrophoretic injection of substrate, e.g. glucose-6-P. A return to 8-10 times less intense excitation conditions used in an earlier prototype microspectrofluorometer, has allowed the observation of sequential changes in the difference spectra (after glucose-6-P minus before) of hydrocarbon-treated cells (e.g. benzo(a)pyrene, dibenzocarbazols). The possible relative contributions of NAD(P)H and hydrocarbon metabolites (or alterations) to such sequential spectra are still under consideration, but the main obstacle to their observation, fading, is removed by less intense excitation.", "contents": "The UV fading of hydrocarbon fluorescence and its prevention for observations in single living cells. Excitation intensities used for standard microspectrofluorometric observations of natural cell fluorescence, i.e. NAD(P)H, lead to fading of hydrocarbon (polycyclic aromatic, heterocyclic) fluorescence in EL2 cells incubated with such compounds. The disappearance of hydrocarbon fluorescence under excitation at 366 nm seems to be an exponential function of time. The fading prevents studies on hydrocarbon metabolization in correlation with intracellular microelectrophoretic injection of substrate, e.g. glucose-6-P. A return to 8-10 times less intense excitation conditions used in an earlier prototype microspectrofluorometer, has allowed the observation of sequential changes in the difference spectra (after glucose-6-P minus before) of hydrocarbon-treated cells (e.g. benzo(a)pyrene, dibenzocarbazols). The possible relative contributions of NAD(P)H and hydrocarbon metabolites (or alterations) to such sequential spectra are still under consideration, but the main obstacle to their observation, fading, is removed by less intense excitation."}
{"id": "PMID:241738", "title": "Mutational biosynthesis of a new antibiotic, streptomutin A, by an idiotroph of Streptomyces griseus.", "content": "Microorganisms producing antibiotics have been genetically converted by earlier workers to mutants which cannot produce antibiotic without supplementation with a moiety of the antibiotic. These antibiotics include neomycin, kanamycin, paromomycin, butirosin, sisomicin, ribostamycin and novobiocin. Success has not been reported for organisms producing guanidinocyclitol antibiotics such as streptomycin. We mutagenized conidia of the streptomycin-producing Streptomyces griseus strain 7-455F3 with nitrosoguanidine at pH 7.0. Non-producers of streptomycin were visually selected by the agar-plug technique using Bacillus subtilis. We successfully isolated mutant MIT-A5 which produces no streptomycin unless streptidine is added to the agar medium. The streptidine-dependent phenotype was confirmed in submerged culture in flasks. Attempts to produce new antibiotics by feeding aminocyclitols to mutant MIT-A5 failed. However a new antibiotic (streptomutin A) was produced by supplementation with the guanidinocyclitol, 2-deoxystreptidine. We propose the term \"mutational biosynthesis\" for the production of new metabolites by the use of mutants blocked in the biosynthetic pathway to the secondary metabolite. We further propose the term \"idiotroph\" to properly describe such mutants.", "contents": "Mutational biosynthesis of a new antibiotic, streptomutin A, by an idiotroph of Streptomyces griseus. Microorganisms producing antibiotics have been genetically converted by earlier workers to mutants which cannot produce antibiotic without supplementation with a moiety of the antibiotic. These antibiotics include neomycin, kanamycin, paromomycin, butirosin, sisomicin, ribostamycin and novobiocin. Success has not been reported for organisms producing guanidinocyclitol antibiotics such as streptomycin. We mutagenized conidia of the streptomycin-producing Streptomyces griseus strain 7-455F3 with nitrosoguanidine at pH 7.0. Non-producers of streptomycin were visually selected by the agar-plug technique using Bacillus subtilis. We successfully isolated mutant MIT-A5 which produces no streptomycin unless streptidine is added to the agar medium. The streptidine-dependent phenotype was confirmed in submerged culture in flasks. Attempts to produce new antibiotics by feeding aminocyclitols to mutant MIT-A5 failed. However a new antibiotic (streptomutin A) was produced by supplementation with the guanidinocyclitol, 2-deoxystreptidine. We propose the term \"mutational biosynthesis\" for the production of new metabolites by the use of mutants blocked in the biosynthetic pathway to the secondary metabolite. We further propose the term \"idiotroph\" to properly describe such mutants."}
{"id": "PMID:241741", "title": "Biological effects of lipoteichoic acids.", "content": "Pneumococcal lipoteichoic acid (Forssman antigen) added to the medium of growing pneumococcal cultures caused chain formation, prevented culture lysis in the stationary phase of growth, and inhibited lysis by penicillin and by the pneumococcal bacteriophage Dp-1.", "contents": "Biological effects of lipoteichoic acids. Pneumococcal lipoteichoic acid (Forssman antigen) added to the medium of growing pneumococcal cultures caused chain formation, prevented culture lysis in the stationary phase of growth, and inhibited lysis by penicillin and by the pneumococcal bacteriophage Dp-1."}
{"id": "PMID:241742", "title": "Peptidoglycan synthesis in L-phase variants of Bacillus licheniformis and Bacillus subtilis.", "content": "Stable L-phase variants isolated from Bacillus licheniformis and Bacillus subtilis, when grown in osmotically stabilized media, do not synthesize peptidoglycan but have been found to accumulate the nucleotide precursors of this polymer. The enzymes involved in the synthesis of these precursors and the later membrane-bound stages of peptidoglycan synthesis have been investigated, and the L-phase variants have been shown to contain lesions, which provide a rational explanation for the absence of peptidoglycan and for the nature of the precursor accumulated. The majority of the L-phase variants contained a single enzymic defect, but two strains were isolated with double lesions. Five out of seven strains examined accumulated uridine 5'-diphosphate (UDP)-MurAc-L-ala-D-glu and were unable to synthesize diaminopimelic acid as a consequence of a defect in aspartate-beta-semialdehyde dehydrogenase activity. Two strains were deficient in UDP-MurAc: L-alanine ligase and accumulated UDP-MurAc. One strain accumulated the complete nucleotide precursor UDP-MurAc-L-ala-D-glu-mA2pm-D-ala-D-ala and was deficient in phospho-N-acetylmuramyl pentapeptide translocase. A second strain also had this lesion, together with defective aspartate-beta-semialdehyde dehydrogenase activity. The other enzymes of peptidoglycan synthesis were present in the L-phase variants, with activities similar to those found in the parent bacilli grown under identical conditions. Membrane preparations from certain of the L-phase variants were also capable of synthesizing the secondary polymers poly(glycerol phosphate) teichoic acid and teichuronic acid and also a polymer of N-acetylglucosamine.", "contents": "Peptidoglycan synthesis in L-phase variants of Bacillus licheniformis and Bacillus subtilis. Stable L-phase variants isolated from Bacillus licheniformis and Bacillus subtilis, when grown in osmotically stabilized media, do not synthesize peptidoglycan but have been found to accumulate the nucleotide precursors of this polymer. The enzymes involved in the synthesis of these precursors and the later membrane-bound stages of peptidoglycan synthesis have been investigated, and the L-phase variants have been shown to contain lesions, which provide a rational explanation for the absence of peptidoglycan and for the nature of the precursor accumulated. The majority of the L-phase variants contained a single enzymic defect, but two strains were isolated with double lesions. Five out of seven strains examined accumulated uridine 5'-diphosphate (UDP)-MurAc-L-ala-D-glu and were unable to synthesize diaminopimelic acid as a consequence of a defect in aspartate-beta-semialdehyde dehydrogenase activity. Two strains were deficient in UDP-MurAc: L-alanine ligase and accumulated UDP-MurAc. One strain accumulated the complete nucleotide precursor UDP-MurAc-L-ala-D-glu-mA2pm-D-ala-D-ala and was deficient in phospho-N-acetylmuramyl pentapeptide translocase. A second strain also had this lesion, together with defective aspartate-beta-semialdehyde dehydrogenase activity. The other enzymes of peptidoglycan synthesis were present in the L-phase variants, with activities similar to those found in the parent bacilli grown under identical conditions. Membrane preparations from certain of the L-phase variants were also capable of synthesizing the secondary polymers poly(glycerol phosphate) teichoic acid and teichuronic acid and also a polymer of N-acetylglucosamine."}
{"id": "PMID:241743", "title": "Enzymology and genetic regulation of a cyclic nucleotide-binding phosphodiesterase-phosphomonoesterase from Aspergillus nidulans.", "content": "A cyclic nucleotide-binding phosphohydrolase that possesses both a phosphomonoesterase and a phosphodiesterase catalytic function has been partially purified from Aspergillus nidulans. The enzyme hydrolyzes both p-nitrophenylphosphate and bis-(p-nitrophenyl)-phosphate. o'-Nucleoside monophosphates are the best physiological phosphomonesterase substrates but 5'- and 2'-nucleoside monophosphates are also hydrolyzed. The enzyme catalyzes the hydrolysis of adenosine 5'-triphosphate, adenosine 5'-diphosphate, and 2',3'- and 3'5'-cyclic nucleotides, but not of ribonucleic acid, deoxyribonucleic acid, or nicotinamide adenine dinucleotide. The enzyme has acid pH optima and is not activated by divalent cations. Nucleosides and nucleotides inhibit the enzyme. Cyclic nucleotides are competitive inhibitors of the phosphodiesterase-phosphomonoesterase. The enzyme can occur extracellularly. The phosphodiesterase-phosphomonoesterase is present at high levels in nitrogen-starved mycelium, and it is strongly repressed during growth in media containing ammonium or glutamine and weakly repressed during growth in glutamate-containing medium. Experiments with various area mutants show that this regulatory gene is involved in the control of the enzyme. No evidence for regulation of the enzyme by carbon or phosphorus starvation has been found.", "contents": "Enzymology and genetic regulation of a cyclic nucleotide-binding phosphodiesterase-phosphomonoesterase from Aspergillus nidulans. A cyclic nucleotide-binding phosphohydrolase that possesses both a phosphomonoesterase and a phosphodiesterase catalytic function has been partially purified from Aspergillus nidulans. The enzyme hydrolyzes both p-nitrophenylphosphate and bis-(p-nitrophenyl)-phosphate. o'-Nucleoside monophosphates are the best physiological phosphomonesterase substrates but 5'- and 2'-nucleoside monophosphates are also hydrolyzed. The enzyme catalyzes the hydrolysis of adenosine 5'-triphosphate, adenosine 5'-diphosphate, and 2',3'- and 3'5'-cyclic nucleotides, but not of ribonucleic acid, deoxyribonucleic acid, or nicotinamide adenine dinucleotide. The enzyme has acid pH optima and is not activated by divalent cations. Nucleosides and nucleotides inhibit the enzyme. Cyclic nucleotides are competitive inhibitors of the phosphodiesterase-phosphomonoesterase. The enzyme can occur extracellularly. The phosphodiesterase-phosphomonoesterase is present at high levels in nitrogen-starved mycelium, and it is strongly repressed during growth in media containing ammonium or glutamine and weakly repressed during growth in glutamate-containing medium. Experiments with various area mutants show that this regulatory gene is involved in the control of the enzyme. No evidence for regulation of the enzyme by carbon or phosphorus starvation has been found."}
{"id": "PMID:241744", "title": "Glutamate dehydrogenase from Escherichia coli: purification and properties.", "content": "Glutamate dehydrogenase (L-glutamate:NADP+ oxidoreductase [deaminating], EC 1.4.1.4) has been purified from Escherichia coli B/r. The purity of the enzyme preparation has been established by polyacrylamide gel electrophoresis, ultracentrifugation, and gel filtration. A molecular weight of 300,000 +/- 20,000 has been calculated for the enzyme from sedimentation equilibrium measurements. Polyacrylamide gel electrophoresis in sodium dodecyl sulfate and sedimentation equilibrium measurements in guanidine hydrochloride have revealed that glutamate dehydrogenase consists of polypeptide chains with the identical molecular weight of 50,000 +/- 5,000. The results of molecular weight determination lead us to propose that glutamate dehydrogenase is a hexamer of subunits with identical molecular weight. We also have studied the stability and kinetics of purified glutamate dehydrogenase. The enzyme remains active when heat treated or when left at room temperature for several months but is inactivated by freezing. The Michaelis constants of glutamate dehydrogenase are 1,100,640, and 40 muM for ammonia, 2-oxoglutarate, and reduced nicotinamide adenine dinucleotide phosphate, respectively.", "contents": "Glutamate dehydrogenase from Escherichia coli: purification and properties. Glutamate dehydrogenase (L-glutamate:NADP+ oxidoreductase [deaminating], EC 1.4.1.4) has been purified from Escherichia coli B/r. The purity of the enzyme preparation has been established by polyacrylamide gel electrophoresis, ultracentrifugation, and gel filtration. A molecular weight of 300,000 +/- 20,000 has been calculated for the enzyme from sedimentation equilibrium measurements. Polyacrylamide gel electrophoresis in sodium dodecyl sulfate and sedimentation equilibrium measurements in guanidine hydrochloride have revealed that glutamate dehydrogenase consists of polypeptide chains with the identical molecular weight of 50,000 +/- 5,000. The results of molecular weight determination lead us to propose that glutamate dehydrogenase is a hexamer of subunits with identical molecular weight. We also have studied the stability and kinetics of purified glutamate dehydrogenase. The enzyme remains active when heat treated or when left at room temperature for several months but is inactivated by freezing. The Michaelis constants of glutamate dehydrogenase are 1,100,640, and 40 muM for ammonia, 2-oxoglutarate, and reduced nicotinamide adenine dinucleotide phosphate, respectively."}
{"id": "PMID:241745", "title": "Isolation and characterization of the newly evolved ebg beta-galactosidase of Escherichia coli K-12.", "content": "The ebg beta-galactosidase of Escherichia coli K-12 strain LC110 has been purified and characterized. Strain LC110 is a Lac+ revertant of a mutant with a deletion of the lacZ beta-galactosidase gene. Its new ebg beta-galactosidase activity was shown to be due to a discrete protein, immunologically unrelated to lacZ beta-galactosidase. Its kinetics of action conformed to those of a simple conventional enzyme. With o-nitrophenyl-beta-D-galactoside as substrate, the Vmax was 11,200 nmol/min per mg of enzyme, the Km was 5 mM, and the activation energy was 12,400 cal/mol. Corresponding values for lacZ beta-galactosidase of wild-type E. coli K-12 were 350,000 nmol/min per mg of enzyme, 1.3 mM, and 8,000 cal/mol. A series of sugars has been examined as competitive inhibitors of ebg beta-galactosidase. Kinetic analyses suggest that ebg beta-galactosidase has a particularly high affinity for galactosamine and gamma-galactonolactone, binds galatose more tightly than lactose, and shows a general preference for monosaccharides rather than beta-galactosides. We conclude that the ebg beta-galactosidase may have arisen by modification of a gene involved with the metabolism of a monosaccharide, possibly a 2-amino sugar.", "contents": "Isolation and characterization of the newly evolved ebg beta-galactosidase of Escherichia coli K-12. The ebg beta-galactosidase of Escherichia coli K-12 strain LC110 has been purified and characterized. Strain LC110 is a Lac+ revertant of a mutant with a deletion of the lacZ beta-galactosidase gene. Its new ebg beta-galactosidase activity was shown to be due to a discrete protein, immunologically unrelated to lacZ beta-galactosidase. Its kinetics of action conformed to those of a simple conventional enzyme. With o-nitrophenyl-beta-D-galactoside as substrate, the Vmax was 11,200 nmol/min per mg of enzyme, the Km was 5 mM, and the activation energy was 12,400 cal/mol. Corresponding values for lacZ beta-galactosidase of wild-type E. coli K-12 were 350,000 nmol/min per mg of enzyme, 1.3 mM, and 8,000 cal/mol. A series of sugars has been examined as competitive inhibitors of ebg beta-galactosidase. Kinetic analyses suggest that ebg beta-galactosidase has a particularly high affinity for galactosamine and gamma-galactonolactone, binds galatose more tightly than lactose, and shows a general preference for monosaccharides rather than beta-galactosides. We conclude that the ebg beta-galactosidase may have arisen by modification of a gene involved with the metabolism of a monosaccharide, possibly a 2-amino sugar."}
{"id": "PMID:241746", "title": "Selective release of a deoxyribonucleic acid-binding factor from the surface of competent pneumococci.", "content": "Methods are described that resulted in the selective release of deoxyribonucleic acid (DNA)-binding factor from the surface of competent pneumococci. The same methods caused a parallel inactivation of the DNA-binding capacity of the extracted bacteria. Genetically or physiologically incompetent pneumococci did not yield binding factor upon exposure to the same methods. The solubilized binding factor appeared to be a protein; it could be assayed by a membrane filter binding procedure. The binding factor had properties reminiscent of those of the DNA receptors of transformable pneumococci (Seto et al., 1975).", "contents": "Selective release of a deoxyribonucleic acid-binding factor from the surface of competent pneumococci. Methods are described that resulted in the selective release of deoxyribonucleic acid (DNA)-binding factor from the surface of competent pneumococci. The same methods caused a parallel inactivation of the DNA-binding capacity of the extracted bacteria. Genetically or physiologically incompetent pneumococci did not yield binding factor upon exposure to the same methods. The solubilized binding factor appeared to be a protein; it could be assayed by a membrane filter binding procedure. The binding factor had properties reminiscent of those of the DNA receptors of transformable pneumococci (Seto et al., 1975)."}
{"id": "PMID:241747", "title": "Serine transhydroxymethylase isoenzymes from a facultative methylotroph.", "content": "Two serine transhydroxymethylase activities have been purified from a facultative methylotrophic bacterium. One enzyme predominates when the organism is grown on methane or methanol as the sole carbon and energy source, whereas the second enzyme is the major isoenzyme found when succinate is used as the sole carbon and energy source. The enzyme from methanol-grown cells is activated by glyoxylate, is not stimulated by Mg2+, Mn2+, or Zn2+, and has four subunits of 50,000 molecular weight each. The enzyme from succinate-grown cells is not activated by glyoxylate and is stimulated by Mg2+, Mn2+, and Zn2+, and sodium dodecyl sulfate-acrylamide gel electrophoresis indicates that this enzyme has subunit molecular weight of 100,000, the same as the molecular weight obtained for the active enzyme. Cells grown in the presence of both methanol and succinate incorporate less methanol carbon per unit time than cells grown on methanol and have a lower specific activity of the glyoxylate-activated enzyme than methanol-grown cells. Adenine, glyoxylate, or trimethoprim in the growth medium causes an increased level of serine transhydroxymethylase in both methanol- and succinate-grown cells by stimulating the synthesis of the glyoxylate-activated enzyme.", "contents": "Serine transhydroxymethylase isoenzymes from a facultative methylotroph. Two serine transhydroxymethylase activities have been purified from a facultative methylotrophic bacterium. One enzyme predominates when the organism is grown on methane or methanol as the sole carbon and energy source, whereas the second enzyme is the major isoenzyme found when succinate is used as the sole carbon and energy source. The enzyme from methanol-grown cells is activated by glyoxylate, is not stimulated by Mg2+, Mn2+, or Zn2+, and has four subunits of 50,000 molecular weight each. The enzyme from succinate-grown cells is not activated by glyoxylate and is stimulated by Mg2+, Mn2+, and Zn2+, and sodium dodecyl sulfate-acrylamide gel electrophoresis indicates that this enzyme has subunit molecular weight of 100,000, the same as the molecular weight obtained for the active enzyme. Cells grown in the presence of both methanol and succinate incorporate less methanol carbon per unit time than cells grown on methanol and have a lower specific activity of the glyoxylate-activated enzyme than methanol-grown cells. Adenine, glyoxylate, or trimethoprim in the growth medium causes an increased level of serine transhydroxymethylase in both methanol- and succinate-grown cells by stimulating the synthesis of the glyoxylate-activated enzyme."}
{"id": "PMID:241749", "title": "Ethanolaminephosphate cytidylyltransferase. Purification and characterization of the enzyme from rat liver.", "content": "Ethanolaminephosphate cytidylyltransferase (EC 2.7.7.14), which catalyzes a central step in phosphatidylethanolamine synthesis, has been purified 1000-fold from a postmicrosomal supernatant from rat liver. The enzyme, which requires a reducing agent, like dithiothreitol, for activity, is stable for weeks at 0-4 degrees when stored in the presence of dithiothreitol and in the pH range 7.5 to 9.0. A molecular weight of 100 to 120 X 10(3) was estimated by gel chromatography on Sephadex G-200. Gel electrophoresis in the presence of sodium dodecyl sulfate gave only one protein band with an apparent molecular weight of 49 to 50 X 10(3). The reaction catalyzed by the enzyme is reversible with a Keq for the forward reaction of 0.46 under the assay conditions. Michaelis constants of 53 and 65 muM were determined for CTP and ethanolaminephosphate, respectively. From the product inhibition pattern an ordered sequential reaction mechanism is proposed, in which CTP is the first substrate to add to the enzyme and CDP-ethanolamine is the last product to be released. The possible role of this reaction in the regulation of phosphatidylethanolamine synthesis in liver is discussed.", "contents": "Ethanolaminephosphate cytidylyltransferase. Purification and characterization of the enzyme from rat liver. Ethanolaminephosphate cytidylyltransferase (EC 2.7.7.14), which catalyzes a central step in phosphatidylethanolamine synthesis, has been purified 1000-fold from a postmicrosomal supernatant from rat liver. The enzyme, which requires a reducing agent, like dithiothreitol, for activity, is stable for weeks at 0-4 degrees when stored in the presence of dithiothreitol and in the pH range 7.5 to 9.0. A molecular weight of 100 to 120 X 10(3) was estimated by gel chromatography on Sephadex G-200. Gel electrophoresis in the presence of sodium dodecyl sulfate gave only one protein band with an apparent molecular weight of 49 to 50 X 10(3). The reaction catalyzed by the enzyme is reversible with a Keq for the forward reaction of 0.46 under the assay conditions. Michaelis constants of 53 and 65 muM were determined for CTP and ethanolaminephosphate, respectively. From the product inhibition pattern an ordered sequential reaction mechanism is proposed, in which CTP is the first substrate to add to the enzyme and CDP-ethanolamine is the last product to be released. The possible role of this reaction in the regulation of phosphatidylethanolamine synthesis in liver is discussed."}
{"id": "PMID:241750", "title": "Refolding of reduced, denatured trypsinogen and trypsin immobilized on Agarose beads.", "content": "The reoxidation of fully reduced and denatured bovine trypsinogen and the regeneration of the native structure can be accomplished if the protein is initially attached to Agarose beads. Reoxidation was performed under aerobic conditions, in the presence of mercaptoethanol and dehydroascorbate or with a mixture of reduced and oxidized glutathione. In 24 hours, the yields of regenerated trypsinogen were 60 to 70% with 0.2 to 0.6 mg of protein bound/ml of gel but 30% or less if greater than 1.7 mg of protein were bound. Rapid reoxidation, with dehydroascorbate as catalyst, gave molecules which could not be converted to active trypsin. However, if the incorrectly folded structures were placed in a mixture of reduced and oxidized glutathione, the molecules underwent disulfide interchange and could continue to refold. The rapidly reoxidized molecules regained their native structure with the same rate and to the same extent as they did initially in the absence of rapid reoxidation. Therefore, the rate-limiting step in the refolding of trypsinogen was disulfide interchange. The regenerated Agarose-bound trypsinogen displayed the usual properties of the native molecule in (a) its conversion to active trypsin by a process of limited proteolysis, (b) the kinetic constants of the activated product toward typical trypsin substrates, and (c) the limited cleavage of 1 disulfide bond with sodium borohydride. Refoldind of immobilized trypsin was also observed with an overall yield of 50%. Trypsin can fold spontaneously to its native structure even though it lacks the NH2-terminal hexapeptide of its precursor.", "contents": "Refolding of reduced, denatured trypsinogen and trypsin immobilized on Agarose beads. The reoxidation of fully reduced and denatured bovine trypsinogen and the regeneration of the native structure can be accomplished if the protein is initially attached to Agarose beads. Reoxidation was performed under aerobic conditions, in the presence of mercaptoethanol and dehydroascorbate or with a mixture of reduced and oxidized glutathione. In 24 hours, the yields of regenerated trypsinogen were 60 to 70% with 0.2 to 0.6 mg of protein bound/ml of gel but 30% or less if greater than 1.7 mg of protein were bound. Rapid reoxidation, with dehydroascorbate as catalyst, gave molecules which could not be converted to active trypsin. However, if the incorrectly folded structures were placed in a mixture of reduced and oxidized glutathione, the molecules underwent disulfide interchange and could continue to refold. The rapidly reoxidized molecules regained their native structure with the same rate and to the same extent as they did initially in the absence of rapid reoxidation. Therefore, the rate-limiting step in the refolding of trypsinogen was disulfide interchange. The regenerated Agarose-bound trypsinogen displayed the usual properties of the native molecule in (a) its conversion to active trypsin by a process of limited proteolysis, (b) the kinetic constants of the activated product toward typical trypsin substrates, and (c) the limited cleavage of 1 disulfide bond with sodium borohydride. Refoldind of immobilized trypsin was also observed with an overall yield of 50%. Trypsin can fold spontaneously to its native structure even though it lacks the NH2-terminal hexapeptide of its precursor."}
{"id": "PMID:241751", "title": "Factors contributing to the inhibition of aspartate aminotransferase by dicarboxylic acids.", "content": "At pH 8.0 aspartate aminotransferase (L-aspartate:2-oxoglutarate aminotransferase, EC 2.6.1.1) reacts with the modified substrate, erythro-beta-hydroxy-L-aspartate, to form a mixture of enzyme-substrate complexes absorbing at 492 nm. A variety of dicarboxylic acids were studied spectrophotometrically as competitive inhibitors of this reaction. All of the inhibitory dicarboxylic acids form a complex with the enzyme, absorbing at 362 nm. In addition, some of the dicarboxylic acids form a protonated complex absorbing at about 435 nm. This complex, which is the conjugate acid of that absorbing at 362 nm, is formed only by those dicarboxylic acids which can assume a configuration in which the two carboxyl groups are positioned as in maleic acid. Bulky substituents, such as aromatic rings or even methyl groups, prevent the formation of the protonated complex, presumably because of steric restrictions at the active site. Substitution of the central carbon atom of glutaric acid by heteroatoms of increasing charge density results in a progressive decrease in inhibitory effectiveness, at pH 8, primarily due to a loss of this pH-dependent stabilization of the enzyme-dicarboxylic acid complex. Acids with an aromatic ring are among the most potent dicarboxylic acid inhibitors of this enzyme in spite of the fact that they do not undergo the pH-dependent stabilization of their enzyme complexes. From these observations it was concluded that the affinity of aspartate aminotransferase for dicarboxylic acids is determined as much by the mechanism of binding as by the solvation and steric effects.", "contents": "Factors contributing to the inhibition of aspartate aminotransferase by dicarboxylic acids. At pH 8.0 aspartate aminotransferase (L-aspartate:2-oxoglutarate aminotransferase, EC 2.6.1.1) reacts with the modified substrate, erythro-beta-hydroxy-L-aspartate, to form a mixture of enzyme-substrate complexes absorbing at 492 nm. A variety of dicarboxylic acids were studied spectrophotometrically as competitive inhibitors of this reaction. All of the inhibitory dicarboxylic acids form a complex with the enzyme, absorbing at 362 nm. In addition, some of the dicarboxylic acids form a protonated complex absorbing at about 435 nm. This complex, which is the conjugate acid of that absorbing at 362 nm, is formed only by those dicarboxylic acids which can assume a configuration in which the two carboxyl groups are positioned as in maleic acid. Bulky substituents, such as aromatic rings or even methyl groups, prevent the formation of the protonated complex, presumably because of steric restrictions at the active site. Substitution of the central carbon atom of glutaric acid by heteroatoms of increasing charge density results in a progressive decrease in inhibitory effectiveness, at pH 8, primarily due to a loss of this pH-dependent stabilization of the enzyme-dicarboxylic acid complex. Acids with an aromatic ring are among the most potent dicarboxylic acid inhibitors of this enzyme in spite of the fact that they do not undergo the pH-dependent stabilization of their enzyme complexes. From these observations it was concluded that the affinity of aspartate aminotransferase for dicarboxylic acids is determined as much by the mechanism of binding as by the solvation and steric effects."}
{"id": "PMID:241752", "title": "A DNA polymerase from embryos of Drosophila melanogaster. Purification and properties.", "content": "The more than 2,300-fold purification of a DNA polymerase from the embryos of Drosophila melanogaster is described. The enzyme, which forms a single band on gel electrophoresis, has a molecular weight of about 87,000 and a pH optimum of 8.5. A divalent metal is required for activity, Mg2+ being preferred with activated DNA, Mn2+ with homopolymer template-primers. The enzyme is inactivated completely by mercurials; polyamines are also inhibitory with certain templates. The most efficient template-primer is activated DNA, but homopolymers such as poly(dA)-oligo(dT), poly(A)-oligo(dT), and poly(A)-oligo(U) are also utilized with high efficiency. The purified enzyme preparations appear to be devoid of nuclease activity when assayed directly with suitable substrates. In addition, neither primer nor product is degraded after prolonged incubation with the enzyme. In accordance with previous observations on other DNA polymerases, the Drosophila enzyme can replicate single-stranded DNA only under conditions of simultaneous transcription by RNA polymerase.", "contents": "A DNA polymerase from embryos of Drosophila melanogaster. Purification and properties. The more than 2,300-fold purification of a DNA polymerase from the embryos of Drosophila melanogaster is described. The enzyme, which forms a single band on gel electrophoresis, has a molecular weight of about 87,000 and a pH optimum of 8.5. A divalent metal is required for activity, Mg2+ being preferred with activated DNA, Mn2+ with homopolymer template-primers. The enzyme is inactivated completely by mercurials; polyamines are also inhibitory with certain templates. The most efficient template-primer is activated DNA, but homopolymers such as poly(dA)-oligo(dT), poly(A)-oligo(dT), and poly(A)-oligo(U) are also utilized with high efficiency. The purified enzyme preparations appear to be devoid of nuclease activity when assayed directly with suitable substrates. In addition, neither primer nor product is degraded after prolonged incubation with the enzyme. In accordance with previous observations on other DNA polymerases, the Drosophila enzyme can replicate single-stranded DNA only under conditions of simultaneous transcription by RNA polymerase."}
{"id": "PMID:241753", "title": "Purification and properties of Bacillus subtilis aspartate transcarbamylase.", "content": "Aspartate transcarbamylase from Bacillus subtilis has been purified to apparent homogeneity. A subunit molecular weight of 33,500 +/- 1,000 was obtained from electrophoresis in polyarcylamide gels containing sodium dodecyl sulfate and from sedimentation equilibrium analysis of the protein dissolved in 6 M guanidine hydrochloride. The molecular weight of the native enzyme was determined to be 102,000 +/- 2,000 by sedimentation velocity and sedimentation equilibrium analysis. Aspartate transcarbamylase thus appears to be a trimeric protein; cross-linking with dimethyl suberimidate and electrophoretic analysis confirmed this structure. B. subtilis aspartate transcarbamylase has an amino acid composition quite similar to that of the catalytic subunit from Escherichia coli aspartate transcarbamylase; only the content of four amino acids is substantially different. The denaturated enzyme has one free sulfhydryl group. Aspartate transcarbamylase exhibited Michaelis-Menten kinetics and was neither inhibited nor activated by nucleotides. Several anions stimulated activity 2- to 5-fold. Immunochemical studies indicated very little similarity between B. subtilis and E. coli aspartate transcarbamylase or E. coli aspartate transcarbamylase catalytic subunit.", "contents": "Purification and properties of Bacillus subtilis aspartate transcarbamylase. Aspartate transcarbamylase from Bacillus subtilis has been purified to apparent homogeneity. A subunit molecular weight of 33,500 +/- 1,000 was obtained from electrophoresis in polyarcylamide gels containing sodium dodecyl sulfate and from sedimentation equilibrium analysis of the protein dissolved in 6 M guanidine hydrochloride. The molecular weight of the native enzyme was determined to be 102,000 +/- 2,000 by sedimentation velocity and sedimentation equilibrium analysis. Aspartate transcarbamylase thus appears to be a trimeric protein; cross-linking with dimethyl suberimidate and electrophoretic analysis confirmed this structure. B. subtilis aspartate transcarbamylase has an amino acid composition quite similar to that of the catalytic subunit from Escherichia coli aspartate transcarbamylase; only the content of four amino acids is substantially different. The denaturated enzyme has one free sulfhydryl group. Aspartate transcarbamylase exhibited Michaelis-Menten kinetics and was neither inhibited nor activated by nucleotides. Several anions stimulated activity 2- to 5-fold. Immunochemical studies indicated very little similarity between B. subtilis and E. coli aspartate transcarbamylase or E. coli aspartate transcarbamylase catalytic subunit."}
{"id": "PMID:241754", "title": "Escherichia coli enterotoxin. Purification and partial characterization.", "content": "Enterotoxin, a diarrheagenic protein elaborated by pathogenic Escherichia coli strains has been isolated from the supernatant of fermenter cultures of E. coli strain P263, a porcine enteropathogen. Purification steps involving Bio-Gel agarose A-5m, Sephadex G-75 chromatography, and preparative isotachophoresis were used in the isolation. The resulting product appears to be pure according to immunoelectrophoretic, disc electrophoretic, ultracentrifugal, and immunologic criteria. The entertoxin has an apparent molecular weight of 102,000 as judged by gel filtration and sodium dodecyl sulfate polyacrylamide gel electrophoresis, and its isoelectric point is 6.90. The isolated product is highly active in inducing experimental diarrhea in adult rabbits and piglets. It also elicits, in small dosage, a marked increase in adenylate cyclase activity in broken cell preparations of cat heart tissue. The enterotoxin activity is acid-labile and is destroyed by heating at 65 degrees for 30 min. It is suggested that the heat-stable enterotoxin material is derived from heat-labile enterotoxin by forming a complex with endotoxin or capsular material present in the culture supernatant.", "contents": "Escherichia coli enterotoxin. Purification and partial characterization. Enterotoxin, a diarrheagenic protein elaborated by pathogenic Escherichia coli strains has been isolated from the supernatant of fermenter cultures of E. coli strain P263, a porcine enteropathogen. Purification steps involving Bio-Gel agarose A-5m, Sephadex G-75 chromatography, and preparative isotachophoresis were used in the isolation. The resulting product appears to be pure according to immunoelectrophoretic, disc electrophoretic, ultracentrifugal, and immunologic criteria. The entertoxin has an apparent molecular weight of 102,000 as judged by gel filtration and sodium dodecyl sulfate polyacrylamide gel electrophoresis, and its isoelectric point is 6.90. The isolated product is highly active in inducing experimental diarrhea in adult rabbits and piglets. It also elicits, in small dosage, a marked increase in adenylate cyclase activity in broken cell preparations of cat heart tissue. The enterotoxin activity is acid-labile and is destroyed by heating at 65 degrees for 30 min. It is suggested that the heat-stable enterotoxin material is derived from heat-labile enterotoxin by forming a complex with endotoxin or capsular material present in the culture supernatant."}
{"id": "PMID:241755", "title": "Affinity column purification of amylases on protein inhibitors from wheat kernel.", "content": "An affinity column was devised for the purification of a large number of amylases inhibited by the albumin from wheat kernel. The procedure involved linking the protein inhibitors from wheat to Sepharose and then specifically eluting the amylase adsorbed to the gel with a high concentration of maltose. By this procedure, the amylases from Tenebrio molitor L. (yellow mealworm) larvae and chicken pancreas were purified to homogeneity with good yields for the first time, as shown by both alkaline and acidic electrophoresis. Human saliva alpha-amylase, purified by the same procedure, showed specific activity and electrophoretic patterns similar to those obtained by other workers with different techniques.", "contents": "Affinity column purification of amylases on protein inhibitors from wheat kernel. An affinity column was devised for the purification of a large number of amylases inhibited by the albumin from wheat kernel. The procedure involved linking the protein inhibitors from wheat to Sepharose and then specifically eluting the amylase adsorbed to the gel with a high concentration of maltose. By this procedure, the amylases from Tenebrio molitor L. (yellow mealworm) larvae and chicken pancreas were purified to homogeneity with good yields for the first time, as shown by both alkaline and acidic electrophoresis. Human saliva alpha-amylase, purified by the same procedure, showed specific activity and electrophoretic patterns similar to those obtained by other workers with different techniques."}
{"id": "PMID:241756", "title": "Gas-chromatographic analysis of 4-prenyl-1,2-diphenyl-3-5-pyrazolidinedione (feprazone) at therapeutic levles in human plasma.", "content": "A specific and sensitive procedure for the determination of prenazone at therapeutic levels in human plasma has been developed. The method involves extraction of the drug from acidified plasma into chloroform. After further purification by back extraction the residue is examined on a gas-liquid chromatograph fitted with a flame ionisation detector. Tetraphenylethylene is used as an internal standard for quantitation by the relative peak height technique. Plasma levels encountered after oral ingestion of therapeutic doses are reported.", "contents": "Gas-chromatographic analysis of 4-prenyl-1,2-diphenyl-3-5-pyrazolidinedione (feprazone) at therapeutic levles in human plasma. A specific and sensitive procedure for the determination of prenazone at therapeutic levels in human plasma has been developed. The method involves extraction of the drug from acidified plasma into chloroform. After further purification by back extraction the residue is examined on a gas-liquid chromatograph fitted with a flame ionisation detector. Tetraphenylethylene is used as an internal standard for quantitation by the relative peak height technique. Plasma levels encountered after oral ingestion of therapeutic doses are reported."}
{"id": "PMID:241757", "title": "Analysis and quantification of ether lipids by chromatographic methods.", "content": "Chromatographic methods, especially thin-layer chromatography (TLC) and gas-liquid chromatography (GLC) are widely used in investigations of the occurrence, molecular structure and metabolism of ether lipids. The application of such techniques to structural analysis and quantification, in combination with methods for the degradation and derivatization of ether lipids, is discussed.", "contents": "Analysis and quantification of ether lipids by chromatographic methods. Chromatographic methods, especially thin-layer chromatography (TLC) and gas-liquid chromatography (GLC) are widely used in investigations of the occurrence, molecular structure and metabolism of ether lipids. The application of such techniques to structural analysis and quantification, in combination with methods for the degradation and derivatization of ether lipids, is discussed."}
{"id": "PMID:241758", "title": "Antibacterial activity of cationic proteins from human granulocytes.", "content": "Human granulocytes contain several cationic proteins with a molecular weight of approximately 25,000, almost identical amino acid composition, and complete immunologic identity. These proteins possess a chymotrypsin-like protease activity at a neutral pH. The antibacterial activity of the cationic proteins has been studied. Bactericidal activities are found against both Gram-positive (Streptococcus faecalis and Staphylococcus aureus) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) organisms. Gram-positive bacteria are, however, the most sensitive. The pH-optimum is near neutrality, and the microbicidal activity shows an inverse relationship to the ionic strength, indicating an ionic interaction between the cationic  proteins and the bacterial surface. The microbicidal effect of the cationic proteins is generally independent of the chymotrypsin-like activity of the same proteins since the activity against several bacterial species is heat stable while the chymotrypsin-like activity is heat labile. The surface properties of S. aureus that are determined by protein A do not seem to influence the susceptibility to cationic proteins. The properties of the Gram-negative envelope of E. coli that determine the susceptibility to the lytic action of serum do not influence the sensitivity to the action of cationic proteins. The present study shows that cationic proteins of human granulocytes represent one potential microbicidal mechanism that is independent of hydrogen peroxide and myeloperoxidase.", "contents": "Antibacterial activity of cationic proteins from human granulocytes. Human granulocytes contain several cationic proteins with a molecular weight of approximately 25,000, almost identical amino acid composition, and complete immunologic identity. These proteins possess a chymotrypsin-like protease activity at a neutral pH. The antibacterial activity of the cationic proteins has been studied. Bactericidal activities are found against both Gram-positive (Streptococcus faecalis and Staphylococcus aureus) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) organisms. Gram-positive bacteria are, however, the most sensitive. The pH-optimum is near neutrality, and the microbicidal activity shows an inverse relationship to the ionic strength, indicating an ionic interaction between the cationic  proteins and the bacterial surface. The microbicidal effect of the cationic proteins is generally independent of the chymotrypsin-like activity of the same proteins since the activity against several bacterial species is heat stable while the chymotrypsin-like activity is heat labile. The surface properties of S. aureus that are determined by protein A do not seem to influence the susceptibility to cationic proteins. The properties of the Gram-negative envelope of E. coli that determine the susceptibility to the lytic action of serum do not influence the sensitivity to the action of cationic proteins. The present study shows that cationic proteins of human granulocytes represent one potential microbicidal mechanism that is independent of hydrogen peroxide and myeloperoxidase."}
{"id": "PMID:241759", "title": "Radioactive labeling of proteins with an iodinated amidination reagent.", "content": "An iodinated phenolic imidoester has been synthesized for the labeling of proteins to high specific activities with radioactive iodine. The main advantage of this two-step labeling method is that it obviates direct contact of the protein with deleterious oxidizing agents, such as chloramine-T, pressent in direct methods of iodinating proteins.", "contents": "Radioactive labeling of proteins with an iodinated amidination reagent. An iodinated phenolic imidoester has been synthesized for the labeling of proteins to high specific activities with radioactive iodine. The main advantage of this two-step labeling method is that it obviates direct contact of the protein with deleterious oxidizing agents, such as chloramine-T, pressent in direct methods of iodinating proteins."}
{"id": "PMID:241760", "title": "Cutaneous immediate hypersensitivity in man: effects of systemically administered adrenergic drugs.", "content": "In in vitro models of hypersensitivity, beta adrenergic drugs inhibit the antigen-induced release of histamine and other mediators from mast cells and basophils. Epinephrine, an agent with both beta and alpha adrenergic properties, is clinically useful for treating immediate hypersensitivity reactions. We examined the effects of intravenously administered adrenergic drugs on cutaneous wheal-and-flare reactions to antigens and histamine in 7 normal men. Both epinephrine and isoproterenol, a beta agonist, inhibited skin reactions produced by antigen or histamine. Phenylephrine, an alpha adrenergic agonist, produced no effect. These results suggest that epinephrine's inhibition of cutaneous immediate hypersensitivity in vivo is mediated by beta, rather than alpha, receptors. This inhibitory effect in vivo is probably not mediated solely in preventing allergic release of inflammatory mediators since the skin reactions to histamine were inhibited as well.", "contents": "Cutaneous immediate hypersensitivity in man: effects of systemically administered adrenergic drugs. In in vitro models of hypersensitivity, beta adrenergic drugs inhibit the antigen-induced release of histamine and other mediators from mast cells and basophils. Epinephrine, an agent with both beta and alpha adrenergic properties, is clinically useful for treating immediate hypersensitivity reactions. We examined the effects of intravenously administered adrenergic drugs on cutaneous wheal-and-flare reactions to antigens and histamine in 7 normal men. Both epinephrine and isoproterenol, a beta agonist, inhibited skin reactions produced by antigen or histamine. Phenylephrine, an alpha adrenergic agonist, produced no effect. These results suggest that epinephrine's inhibition of cutaneous immediate hypersensitivity in vivo is mediated by beta, rather than alpha, receptors. This inhibitory effect in vivo is probably not mediated solely in preventing allergic release of inflammatory mediators since the skin reactions to histamine were inhibited as well."}
{"id": "PMID:241766", "title": "Release of bound immunoglobulin from SSPE brain by acid elution.", "content": "SSPE brain homogenate extracted at pH 7.4 yields immunoglobulin with a 4- to 5-fold greater hemagglutination inhibition activity per microgram of IgG than serum from the same patient. Serial washing of the homogenate results in a low level steady-state release of IgG. Elution of the washed sediment with pH 2.5, 0.1 M glycine buffer results in a 2- to 3-fold increase in recovery of hemagglutination inhibition activity with a greater hemagglutination inhibition activity per milligram of IgG than the IgG recovered by phosphate-saline extraction at pH 7.4.", "contents": "Release of bound immunoglobulin from SSPE brain by acid elution. SSPE brain homogenate extracted at pH 7.4 yields immunoglobulin with a 4- to 5-fold greater hemagglutination inhibition activity per microgram of IgG than serum from the same patient. Serial washing of the homogenate results in a low level steady-state release of IgG. Elution of the washed sediment with pH 2.5, 0.1 M glycine buffer results in a 2- to 3-fold increase in recovery of hemagglutination inhibition activity with a greater hemagglutination inhibition activity per milligram of IgG than the IgG recovered by phosphate-saline extraction at pH 7.4."}
{"id": "PMID:241767", "title": "EAC4 and EAC14 production without purified Ci.", "content": "EAC4 and EAC14 of high activity were prepared by treating sensitized red cells with human or guinea pig serum in the presence of TTHA, a chelating agent whid at low pH to maximize C1 and C4 activity and to minimize C3 contamination. Cells prepared with guinea pig complement were contaminated with C2, which could be decayed away at 37 degrees C. Cells sensitized with IgG antibody were more reactive than those sensitized with whole serum or with IgM, and preparations made with TTHA-complement were more reactive than those prepared with purified C1 plus EDTA-complement. EAC14 stored at 0 degrees C for 3 weeks lost very little activity.", "contents": "EAC4 and EAC14 production without purified Ci. EAC4 and EAC14 of high activity were prepared by treating sensitized red cells with human or guinea pig serum in the presence of TTHA, a chelating agent whid at low pH to maximize C1 and C4 activity and to minimize C3 contamination. Cells prepared with guinea pig complement were contaminated with C2, which could be decayed away at 37 degrees C. Cells sensitized with IgG antibody were more reactive than those sensitized with whole serum or with IgM, and preparations made with TTHA-complement were more reactive than those prepared with purified C1 plus EDTA-complement. EAC14 stored at 0 degrees C for 3 weeks lost very little activity."}
{"id": "PMID:241768", "title": "Physical separation of \"suppressor\" from \"helper\" thymocytes.", "content": "Thymocytes from 1-month-old NZB/W mice were separated at unit gravity and then studied for helper or suppressor effects in a GVH assay. Thymocytes with a settling rate of 4 to 6 mm/hr suppressed but did not help. In contrast, help but no suppression characterized thymocytes settling at 6 to 10 mm/hr. Thus helper and suppressor thymocytes in this GVH assay were physically separated.", "contents": "Physical separation of \"suppressor\" from \"helper\" thymocytes. Thymocytes from 1-month-old NZB/W mice were separated at unit gravity and then studied for helper or suppressor effects in a GVH assay. Thymocytes with a settling rate of 4 to 6 mm/hr suppressed but did not help. In contrast, help but no suppression characterized thymocytes settling at 6 to 10 mm/hr. Thus helper and suppressor thymocytes in this GVH assay were physically separated."}
{"id": "PMID:241770", "title": "Pharmacokinetic characteristics of doxycycline accumulation in normal and severely diseased kidneys.", "content": "Intrarenal concentrations of doxycycline were measured in 48 normal canine kidneys during wide variations in urine pH and the systemic state of hydration of the experimental animals. The results were compared with the renal parenchymal levels achieved in 10 severely diseased human kidneys. Although the state of hydration, the urine pH, and renal disease all significantly influenced the urinary concentrations and rate of renal clearance of doxycycline, there was no detectable difference between concentrations in normal renal tissue and those in severely diseased kidneys. This result is in contradistinction of the findings for previously evaluated antibiotics. The levels of doxycycline measured in renal tissue averaged twice the concentration in serum without notable difference among levels in renal cortex, medulla, and papilla. Prospective clinical trials will be necessary for identification of any solid correlation between the remarkable characteristics of accumulation of doxycycline in diseased renal parenchymal tissue and the clinical, therapeutic importance of such an observation.", "contents": "Pharmacokinetic characteristics of doxycycline accumulation in normal and severely diseased kidneys. Intrarenal concentrations of doxycycline were measured in 48 normal canine kidneys during wide variations in urine pH and the systemic state of hydration of the experimental animals. The results were compared with the renal parenchymal levels achieved in 10 severely diseased human kidneys. Although the state of hydration, the urine pH, and renal disease all significantly influenced the urinary concentrations and rate of renal clearance of doxycycline, there was no detectable difference between concentrations in normal renal tissue and those in severely diseased kidneys. This result is in contradistinction of the findings for previously evaluated antibiotics. The levels of doxycycline measured in renal tissue averaged twice the concentration in serum without notable difference among levels in renal cortex, medulla, and papilla. Prospective clinical trials will be necessary for identification of any solid correlation between the remarkable characteristics of accumulation of doxycycline in diseased renal parenchymal tissue and the clinical, therapeutic importance of such an observation."}
{"id": "PMID:241771", "title": "In vitro and in vivo evaluation of change of local pH on bacteria in C.S.O.M.", "content": "An in vitro study has shown a high bactericidal activity of 2 per cent acetic acid. An in vitro study in 400 cases of C.S.O.M. has shown that conservative treatment of C.S.O.M. by pH change with 2 per cent acetic acid is better than antibiotic ear drops alone. However, combined therapy (pH change plus antibiotic ear drops) is definitely superior to single treatment by either of the two methods. Two per cent acetic acid is well tolerated by the middle ear mucosa except in 1 per cent cases, where its use had to be discontinued because of irritation. The use of 2 per cent acetic acid is highly recommended, particularly for poor nations, because of its negligible cost as compared to antibiotic ear drops.", "contents": "In vitro and in vivo evaluation of change of local pH on bacteria in C.S.O.M. An in vitro study has shown a high bactericidal activity of 2 per cent acetic acid. An in vitro study in 400 cases of C.S.O.M. has shown that conservative treatment of C.S.O.M. by pH change with 2 per cent acetic acid is better than antibiotic ear drops alone. However, combined therapy (pH change plus antibiotic ear drops) is definitely superior to single treatment by either of the two methods. Two per cent acetic acid is well tolerated by the middle ear mucosa except in 1 per cent cases, where its use had to be discontinued because of irritation. The use of 2 per cent acetic acid is highly recommended, particularly for poor nations, because of its negligible cost as compared to antibiotic ear drops."}
{"id": "PMID:241774", "title": "Common dental emergencies which may be encountered by the family physician.", "content": "Dental emergencies are common in everyday practice, and the family physician may frequently be called upon to evaluate and, at times, to provide initial care for such problems. This article acquaints the family physician with diagnosis and treatment of the most common dental emergencies: disorders secondary to trauma, including soft tissue laceration, fracture or displacement of teeth, and bone fractures; and severe pain related to acute alveolar infection.", "contents": "Common dental emergencies which may be encountered by the family physician. Dental emergencies are common in everyday practice, and the family physician may frequently be called upon to evaluate and, at times, to provide initial care for such problems. This article acquaints the family physician with diagnosis and treatment of the most common dental emergencies: disorders secondary to trauma, including soft tissue laceration, fracture or displacement of teeth, and bone fractures; and severe pain related to acute alveolar infection."}
{"id": "PMID:241777", "title": "Neurobiology of Stomotoca. I. Action systems.", "content": "The layout of nerves, muscles, and conducting epithelia is described for the simple hydrozoan medusa Stomotoca. Comparisons are drawn with Sarsia and other recently studied forms. The major action systems are those responsible for swimming, crumpling (protective involution), tentacle posture, pointing (unilateral reciprocal flexions of the manubrium and margin), and visceral movements (barely mentioned). Crumpling is a simple summating response in this species. Crumpling and pointing are considered to use the same effectors but different conduction pathways. New histological results include the demonstration of a nerve plexus running through the endodermal canal system and a nerve plexus in the ectoderm encircling the peduncle. Special attention is given to the distribution of synapses and gap junctions, as possible trasmission pathways in behavioral responses. Some details are included on organization within the marginal nerve rings.", "contents": "Neurobiology of Stomotoca. I. Action systems. The layout of nerves, muscles, and conducting epithelia is described for the simple hydrozoan medusa Stomotoca. Comparisons are drawn with Sarsia and other recently studied forms. The major action systems are those responsible for swimming, crumpling (protective involution), tentacle posture, pointing (unilateral reciprocal flexions of the manubrium and margin), and visceral movements (barely mentioned). Crumpling is a simple summating response in this species. Crumpling and pointing are considered to use the same effectors but different conduction pathways. New histological results include the demonstration of a nerve plexus running through the endodermal canal system and a nerve plexus in the ectoderm encircling the peduncle. Special attention is given to the distribution of synapses and gap junctions, as possible trasmission pathways in behavioral responses. Some details are included on organization within the marginal nerve rings."}
{"id": "PMID:241778", "title": "Neurobiology of Stomotoca. II. Pacemakers and conduction pathways.", "content": "Evidence is presented for separate conduction pathways for swimming and for tentacle coordination in the marginal nerves of the jellyfish Stomotoca. The effector muscles are fired through junctions sensitive to excess Mg++, probably represented by the neuromuscular synapses observed by electron microscopy. The swimming effector (striated muscle) fires one-to-one with nerve input signals and myoid conduction occurs. Tentacle responses (smooth muscle contractions) involve facilitation, presumably at the neuro-effector junction; responses are graded and nonpropagating. Electrical correlates of two further conducting systems using the marginal nerves have been recorded. Their functions are unknown. One, the bridge system, extends up the four radii and encircles the peduncle; the other (ring system) is confined to the margin. A fifth conducting system is inferred in the case of the pointing response and its distribution is plotted. Signals have not been obtained from it. Pointing is accompanied by a burst of muscle potentials in the radial smooth muscles and is exhibited after a lengthy latency, indicating a local pacemaker. A sixth conducting pathway is the epithelial system, which mediates crumpling, a response involving the radial muscles without pacemaker intervention. Characteristic conduction velocities and wave forms are noted for the first four systems and for epithelial pulses. All systems, except perhaps the pointing conduction system, through-conduct under excess Mg++. Spontaneous activity patterns are described for the swimming, tentacle pulse, and ring systems. Abrupt increases in light intensity inhibit spontaneous activity, sudden decreases augmenting it. In the absence of specialized photoreceptors, light is presumed to act directly on central neurons. Epithelial pulses inhibit swimming, apparently by blocking the generation or conduction of the primary nervous events. This observation, taken in conjunction with evidence of feedback inhibition of the primary swimming system by the cells it fires, is discussed in relation to possible mechanisms whereby the output of nerve cells might be altered by activity in the excitable epithelial cells which envelop them.", "contents": "Neurobiology of Stomotoca. II. Pacemakers and conduction pathways. Evidence is presented for separate conduction pathways for swimming and for tentacle coordination in the marginal nerves of the jellyfish Stomotoca. The effector muscles are fired through junctions sensitive to excess Mg++, probably represented by the neuromuscular synapses observed by electron microscopy. The swimming effector (striated muscle) fires one-to-one with nerve input signals and myoid conduction occurs. Tentacle responses (smooth muscle contractions) involve facilitation, presumably at the neuro-effector junction; responses are graded and nonpropagating. Electrical correlates of two further conducting systems using the marginal nerves have been recorded. Their functions are unknown. One, the bridge system, extends up the four radii and encircles the peduncle; the other (ring system) is confined to the margin. A fifth conducting system is inferred in the case of the pointing response and its distribution is plotted. Signals have not been obtained from it. Pointing is accompanied by a burst of muscle potentials in the radial smooth muscles and is exhibited after a lengthy latency, indicating a local pacemaker. A sixth conducting pathway is the epithelial system, which mediates crumpling, a response involving the radial muscles without pacemaker intervention. Characteristic conduction velocities and wave forms are noted for the first four systems and for epithelial pulses. All systems, except perhaps the pointing conduction system, through-conduct under excess Mg++. Spontaneous activity patterns are described for the swimming, tentacle pulse, and ring systems. Abrupt increases in light intensity inhibit spontaneous activity, sudden decreases augmenting it. In the absence of specialized photoreceptors, light is presumed to act directly on central neurons. Epithelial pulses inhibit swimming, apparently by blocking the generation or conduction of the primary nervous events. This observation, taken in conjunction with evidence of feedback inhibition of the primary swimming system by the cells it fires, is discussed in relation to possible mechanisms whereby the output of nerve cells might be altered by activity in the excitable epithelial cells which envelop them."}
{"id": "PMID:241779", "title": "Occurrence of Diplococcus pneumoniae in the upper respiratory tract of children.", "content": "The patterns of colonization of D. pneumoniae were studied over a 46-month period in a group of young children in a day-care center. Forty-four percent of nasal cultures yielded D. pneumoniae. The most frequently isolated serotypes--6, 19, and 23--accounted for 49% of the isolates; the nine most common serotypes included 80% of the isolates. Individual serotypes frequently were carried for several months. Reacquisition of a serotype previously carried occurred frequently. There was limited spread of serotypes among the children despite prolonged contact.", "contents": "Occurrence of Diplococcus pneumoniae in the upper respiratory tract of children. The patterns of colonization of D. pneumoniae were studied over a 46-month period in a group of young children in a day-care center. Forty-four percent of nasal cultures yielded D. pneumoniae. The most frequently isolated serotypes--6, 19, and 23--accounted for 49% of the isolates; the nine most common serotypes included 80% of the isolates. Individual serotypes frequently were carried for several months. Reacquisition of a serotype previously carried occurred frequently. There was limited spread of serotypes among the children despite prolonged contact."}
{"id": "PMID:241780", "title": "Intestine of Ascaris: oxygen consumption, fermentation acids, and anaerobic synthesis of protein.", "content": "The oxygen uptakes by pieces of gut from the porcine roundworm, Ascaris suum, under Po2 10 to 710 torr were from 0.6 to 3.0 mul/mg dry wt/hr (Qo2). Increasing concentrations of tissue, 30 to 90 mg (dry wt/3 ml) decreased Qo2 in air from 1.9 to 1.1 and only technical grade catalase was found to relieve this inhibition. Conversely aerobic fermentation, judged by acid production, was directly proportional to the amount of tissue present: the acids from this fermentation were 2-methyl-butyric (1% of the total), succinic (8%), propionic (40%), and acetic (51%). Glucose did not increase Qo2 but it doubled the incorporation of labeled carbon into protein from glycine-1-14C. Judged by this, protein synthesis proceeded at the same rate under low Po2 (0.01 torr) as under air.", "contents": "Intestine of Ascaris: oxygen consumption, fermentation acids, and anaerobic synthesis of protein. The oxygen uptakes by pieces of gut from the porcine roundworm, Ascaris suum, under Po2 10 to 710 torr were from 0.6 to 3.0 mul/mg dry wt/hr (Qo2). Increasing concentrations of tissue, 30 to 90 mg (dry wt/3 ml) decreased Qo2 in air from 1.9 to 1.1 and only technical grade catalase was found to relieve this inhibition. Conversely aerobic fermentation, judged by acid production, was directly proportional to the amount of tissue present: the acids from this fermentation were 2-methyl-butyric (1% of the total), succinic (8%), propionic (40%), and acetic (51%). Glucose did not increase Qo2 but it doubled the incorporation of labeled carbon into protein from glycine-1-14C. Judged by this, protein synthesis proceeded at the same rate under low Po2 (0.01 torr) as under air."}
{"id": "PMID:241782", "title": "Sympathetic neurotransmitter metabolism in Hirschsprung's disease.", "content": "Tyrosine hydroxylase activity was measured in high speed supernatants obtained from full thickness segments of aganglionic and ganglionic colon of three children with Hirschsprung's disease. Tyrosine hydroxylase activity expressed as pmole DOPA/mg protein/min was 0.93 +/- 0.16 in ganglionic and 2.67 +/- 0.21 in aganglionic colon. Tyrosine hydroxylase activity in ganglionic colon rose to 2.29 +/- 0.11 following calcium stimulation (100 muM) but could not be further increased in aganglionic colon. Addition of norepinephrine (2 X 10(-4) M) to tissue homogenates inhibited tyrosine hydroxylase activity in ganglionic colon by 57 +/- 8% but only by 14 +/- 3% in aganglionic colon, suggesting that the enzyme present in aganglionic colon is insensitive to feedback inhibition by endogenous norepinephrine. The elevation of tyrosine hydroxylase activity in aganglionic colon and its insensitivity to calcium stimulation and norepinephrine inhibition is further evidence of sympathetic overactivity in the aganglionic colon and suggests a basic enzymatic abnormality in the pathogenesis of Hirschsprung's disease.", "contents": "Sympathetic neurotransmitter metabolism in Hirschsprung's disease. Tyrosine hydroxylase activity was measured in high speed supernatants obtained from full thickness segments of aganglionic and ganglionic colon of three children with Hirschsprung's disease. Tyrosine hydroxylase activity expressed as pmole DOPA/mg protein/min was 0.93 +/- 0.16 in ganglionic and 2.67 +/- 0.21 in aganglionic colon. Tyrosine hydroxylase activity in ganglionic colon rose to 2.29 +/- 0.11 following calcium stimulation (100 muM) but could not be further increased in aganglionic colon. Addition of norepinephrine (2 X 10(-4) M) to tissue homogenates inhibited tyrosine hydroxylase activity in ganglionic colon by 57 +/- 8% but only by 14 +/- 3% in aganglionic colon, suggesting that the enzyme present in aganglionic colon is insensitive to feedback inhibition by endogenous norepinephrine. The elevation of tyrosine hydroxylase activity in aganglionic colon and its insensitivity to calcium stimulation and norepinephrine inhibition is further evidence of sympathetic overactivity in the aganglionic colon and suggests a basic enzymatic abnormality in the pathogenesis of Hirschsprung's disease."}
{"id": "PMID:241783", "title": "Accelerated reattachment with cementogenesis to dentin, demineralized in situ. I. Optimum range.", "content": "This study confirms an original report describing accelerated reattachment with cementogenesis to root dentin, surgically exposed and demineralized in situ. It additionally describes results of 250 experiments on over 1000 teeth in mongrel dogs and cats designed to identify an optimum range of demineralization related to type of agent, pH, and time of application. This optimum range consistently induces flap reattachment with cementogenesis, while demineralization rates above and below this range enhance reattachment relative to undermineralized controls, but do not consistently induce new cementum. Although most controls demonstrated some reattachment with partial cementogenesis, none produced complete repair as did properly demineralized root surfaces and approximately one-third showed spithelial migration to the apical borders of the wound. No demineralized teeth demonstrated this control result. Small species differences in the response to root demineralization and the degree of hypermineralization of roots adjacent to chronic periodontal pockets, may make optimum ranges determined in this animal study slightly low for human pocket reaattachment techniques.", "contents": "Accelerated reattachment with cementogenesis to dentin, demineralized in situ. I. Optimum range. This study confirms an original report describing accelerated reattachment with cementogenesis to root dentin, surgically exposed and demineralized in situ. It additionally describes results of 250 experiments on over 1000 teeth in mongrel dogs and cats designed to identify an optimum range of demineralization related to type of agent, pH, and time of application. This optimum range consistently induces flap reattachment with cementogenesis, while demineralization rates above and below this range enhance reattachment relative to undermineralized controls, but do not consistently induce new cementum. Although most controls demonstrated some reattachment with partial cementogenesis, none produced complete repair as did properly demineralized root surfaces and approximately one-third showed spithelial migration to the apical borders of the wound. No demineralized teeth demonstrated this control result. Small species differences in the response to root demineralization and the degree of hypermineralization of roots adjacent to chronic periodontal pockets, may make optimum ranges determined in this animal study slightly low for human pocket reaattachment techniques."}
{"id": "PMID:241784", "title": "The difference in activity between (+)- and (-)-methadone is intrinsic and not due to a difference in metabolism.", "content": "The disposition and metabolism of (+)- and (-)-methadone has been compared in rats. At equal molecular doses, somewhat higher plasma levels of (-)-isomer were observed. At equal analgesic doses, brain and plasma concentrations of (+)-methadone were at least 25 times greater than those of (-)-methadone. No qualitative differences were observed between isomers with respect to in vivo metabolic pattern or in vitro N-demethylation rates. The results strongly support the conclusion that the large differences in analgesic potency between the isomers is due to an intrinsic difference in pharmacologic properties and is not related to a difference in disposition or metabolism.", "contents": "The difference in activity between (+)- and (-)-methadone is intrinsic and not due to a difference in metabolism. The disposition and metabolism of (+)- and (-)-methadone has been compared in rats. At equal molecular doses, somewhat higher plasma levels of (-)-isomer were observed. At equal analgesic doses, brain and plasma concentrations of (+)-methadone were at least 25 times greater than those of (-)-methadone. No qualitative differences were observed between isomers with respect to in vivo metabolic pattern or in vitro N-demethylation rates. The results strongly support the conclusion that the large differences in analgesic potency between the isomers is due to an intrinsic difference in pharmacologic properties and is not related to a difference in disposition or metabolism."}
{"id": "PMID:241785", "title": "Binding of chlorpromazine and imipramine to red cells, albumin, lipoproteins and other blood components.", "content": "The binding of model drugs to human blood and individual blood components has been determined by equilibrium dialysis and expressed in terms of classes of binding sites, association constants and binding capacities. Chlorpromazine and imipramine are bound to three major components: membranes of red cells, albumin, and lipoproteins. The affinity and capacity of lipoprotein binding is at least as high as that of albumin and is equally distributed on HDL, LDL, VLDL, and on the chylomicrons. White blood cells and platelets are of minor importance in terms of binding capacity. No binding was detected with gamma-globulins or alpha- or beta-globulins other than lipoproteins. In contrast, salicylic acid was not bound to red cells or lipoproteins.", "contents": "Binding of chlorpromazine and imipramine to red cells, albumin, lipoproteins and other blood components. The binding of model drugs to human blood and individual blood components has been determined by equilibrium dialysis and expressed in terms of classes of binding sites, association constants and binding capacities. Chlorpromazine and imipramine are bound to three major components: membranes of red cells, albumin, and lipoproteins. The affinity and capacity of lipoprotein binding is at least as high as that of albumin and is equally distributed on HDL, LDL, VLDL, and on the chylomicrons. White blood cells and platelets are of minor importance in terms of binding capacity. No binding was detected with gamma-globulins or alpha- or beta-globulins other than lipoproteins. In contrast, salicylic acid was not bound to red cells or lipoproteins."}
{"id": "PMID:241786", "title": "Mechanism of induction of hepatic microsomal drug metabolizing enzymes by a series of barbiturates.", "content": "The inducing effect of certain barbiturates (secobarbitone, thiopentone, pentobarbitone, allobarbitone, phenobarbitone and barbitone) on the levels of the hepatic microsomal drug-metabolizing enzymes has been studied in the rat both in vivo and in vitro. The extent of induction was related to the plasma half-lives of the barbiturates; compounds with low rates of metabolism and long half-lives were the most potent inducing agents. The latter (phenobarbitone, pentobarbitone and allobarbitone) were shown by spectral technique to interact with cytochrome P-450 suggesting that their mechanism of enzyme induction was 'substrate induction' in type. Barbiturates containing an allyl group (secobarbitone and allobarbitone) had a weaker inducing effect than expected, possibly due to their destruction of cytochrome P-450. Despite its short plasma half-life of 0-5 h thiopentone was a relatively potent inducer probably due to its metabolism to pentobarbitone, which has a much longer plasma half-life (1-3 h). Barbitone is an effective inducer of the drug-metabolizing enzymes, yet does not interact spectrally with cytochrome P-450; this is in accord with the observations that although there are increases in NADPH-cytochrome c reductase and cytochrome b5, following administration of barbitone there is no increase in cytochrome P-450. Barbiturate pretreatment does not affect the activities of glucose-6-phosphatase, glucose-6-phosphate dehydrogenase or 6-phosphogluconate dehydrogenase.", "contents": "Mechanism of induction of hepatic microsomal drug metabolizing enzymes by a series of barbiturates. The inducing effect of certain barbiturates (secobarbitone, thiopentone, pentobarbitone, allobarbitone, phenobarbitone and barbitone) on the levels of the hepatic microsomal drug-metabolizing enzymes has been studied in the rat both in vivo and in vitro. The extent of induction was related to the plasma half-lives of the barbiturates; compounds with low rates of metabolism and long half-lives were the most potent inducing agents. The latter (phenobarbitone, pentobarbitone and allobarbitone) were shown by spectral technique to interact with cytochrome P-450 suggesting that their mechanism of enzyme induction was 'substrate induction' in type. Barbiturates containing an allyl group (secobarbitone and allobarbitone) had a weaker inducing effect than expected, possibly due to their destruction of cytochrome P-450. Despite its short plasma half-life of 0-5 h thiopentone was a relatively potent inducer probably due to its metabolism to pentobarbitone, which has a much longer plasma half-life (1-3 h). Barbitone is an effective inducer of the drug-metabolizing enzymes, yet does not interact spectrally with cytochrome P-450; this is in accord with the observations that although there are increases in NADPH-cytochrome c reductase and cytochrome b5, following administration of barbitone there is no increase in cytochrome P-450. Barbiturate pretreatment does not affect the activities of glucose-6-phosphatase, glucose-6-phosphate dehydrogenase or 6-phosphogluconate dehydrogenase."}
{"id": "PMID:241787", "title": "Effects of a human plasma fraction on the release of chemotactic factors and anaphylatoxin from complement.", "content": "A fraction prepared from normal human plasma inhibits the release of chemotactic factors and anaphylatoxin when complement is activated by the alternate but not by the classical pathway. The fraction gave no interference with the actions of the released substances on either leucocytes or guinea-pig isolated ileum. The possible relation of this effect to the mechanism of the anti-inflammatory actions of the plasma fraction is discussed.", "contents": "Effects of a human plasma fraction on the release of chemotactic factors and anaphylatoxin from complement. A fraction prepared from normal human plasma inhibits the release of chemotactic factors and anaphylatoxin when complement is activated by the alternate but not by the classical pathway. The fraction gave no interference with the actions of the released substances on either leucocytes or guinea-pig isolated ileum. The possible relation of this effect to the mechanism of the anti-inflammatory actions of the plasma fraction is discussed."}
{"id": "PMID:241788", "title": "The surface activity of some antihistamines at the air-solution interface.", "content": "The surface activity of some antihistamines at the air-solution interface has been examined. Change of the counterion associated with the drug from chloride to maleate or chloro-theophyllinate considerably decreased the critical micelle concentration and increased the surface activity. The effect on surface activity of changes in the nature of the hydrophobic and hydrophilic groups have also been evaluated.", "contents": "The surface activity of some antihistamines at the air-solution interface. The surface activity of some antihistamines at the air-solution interface has been examined. Change of the counterion associated with the drug from chloride to maleate or chloro-theophyllinate considerably decreased the critical micelle concentration and increased the surface activity. The effect on surface activity of changes in the nature of the hydrophobic and hydrophilic groups have also been evaluated."}
{"id": "PMID:241789", "title": "The influence of polyvinylpyrrolidone on the dissolution properties of hydroflumethiazide.", "content": "The incorporation of hydroflumethiazide with polyvinylpyrrolidone (PVP) was found to retard and to enhance the dissolution of the drug from compressed discs, the magnitude of the effect being dependent on the proportion of PVP present and its method of incorporation. The most active system dissolved sixteen times faster than pure hydroflumethiazide. Low concentrations of PVP were also found to decrease the apparent solubility of hydroflumethiazide while at high concentrations solubility was enhanced. X-ray and infrared analysis of systems suggested the presence of an amorphous form of hydroflumethiazide in coprecipitate systems. The dissolution data were consistent with a physical model which takes account of the roles played by crystalline and amorphous hydroflumethiazide together with the complexing and crystal growth inhibiting effect of PVP on hydroflumethiazide.", "contents": "The influence of polyvinylpyrrolidone on the dissolution properties of hydroflumethiazide. The incorporation of hydroflumethiazide with polyvinylpyrrolidone (PVP) was found to retard and to enhance the dissolution of the drug from compressed discs, the magnitude of the effect being dependent on the proportion of PVP present and its method of incorporation. The most active system dissolved sixteen times faster than pure hydroflumethiazide. Low concentrations of PVP were also found to decrease the apparent solubility of hydroflumethiazide while at high concentrations solubility was enhanced. X-ray and infrared analysis of systems suggested the presence of an amorphous form of hydroflumethiazide in coprecipitate systems. The dissolution data were consistent with a physical model which takes account of the roles played by crystalline and amorphous hydroflumethiazide together with the complexing and crystal growth inhibiting effect of PVP on hydroflumethiazide."}
{"id": "PMID:241790", "title": "Effects of hardness on the disintegration time and the dissolution rate of uncoated caffeine tablets.", "content": "The effects of hardness on disintegration and dissolution characteristics of uncoated caffeine tablets made at eight different pressure levels were studied. The disintegration times were determined using the J.P. VIII procedure with disks and the dissolution rate measurements were performed with the U.S.P.XVIII procedure (U.S.P. method) and the J.P. VIII disintegration test apparatus (J.P. method). A good correlation between the hardness and the disintegration times was obtained. The dissolution rate constants were determined from the equation of Noyes & Whitney (1897) and a good correlation between the hardness and the dissolution rate constants was obtained. The hardness governed the dissolution over all the stages from tablet to the smallest particles after the breakage by disintegration. The dissolution rates of the J.P. method were greater than those of the U.S.P. method.", "contents": "Effects of hardness on the disintegration time and the dissolution rate of uncoated caffeine tablets. The effects of hardness on disintegration and dissolution characteristics of uncoated caffeine tablets made at eight different pressure levels were studied. The disintegration times were determined using the J.P. VIII procedure with disks and the dissolution rate measurements were performed with the U.S.P.XVIII procedure (U.S.P. method) and the J.P. VIII disintegration test apparatus (J.P. method). A good correlation between the hardness and the disintegration times was obtained. The dissolution rate constants were determined from the equation of Noyes & Whitney (1897) and a good correlation between the hardness and the dissolution rate constants was obtained. The hardness governed the dissolution over all the stages from tablet to the smallest particles after the breakage by disintegration. The dissolution rates of the J.P. method were greater than those of the U.S.P. method."}
{"id": "PMID:241805", "title": "Evidence for a clorgyline-resistant monoamine metabolizing activity in the rat heart.", "content": "When benzylamine was used as substrate, a component of the total monoamine oxidase (MAO) activity in the rat heart was found to be resistant to inhibition by clorgyline. The proportion of the total activity represented by this component, decreased as the rat grew. It was also inhibited by both semicarbazide and isoniazid but not by potassium cyanide. Inhibitor studies with MAO in subcellular fractions showed that this component was more concentrated in the microsomal and soluble fractions. However, it could not be concluded that the activity was entirely a soluble enzyme. Determination of quasi-Michaelis constants (\"Km\") for total benzylamine oxidizing activity revealed a high (\"Km\" of approximately 10(-5)M) and low (\"Km\" of approximately 5 X 10(-4)M) affinity component. The high affinity component was inhibited by semicarbazide and the low affinity component by clorgyline. In the presence of 10(-3)M clorgyline, the high affinity component showed substrate inhibition at higher substrate concentrations. The possibility is discussed that the clorgyline-resistant activity is due to an amine-oxidizing activity distinct from mitochondrial MAO.", "contents": "Evidence for a clorgyline-resistant monoamine metabolizing activity in the rat heart. When benzylamine was used as substrate, a component of the total monoamine oxidase (MAO) activity in the rat heart was found to be resistant to inhibition by clorgyline. The proportion of the total activity represented by this component, decreased as the rat grew. It was also inhibited by both semicarbazide and isoniazid but not by potassium cyanide. Inhibitor studies with MAO in subcellular fractions showed that this component was more concentrated in the microsomal and soluble fractions. However, it could not be concluded that the activity was entirely a soluble enzyme. Determination of quasi-Michaelis constants (\"Km\") for total benzylamine oxidizing activity revealed a high (\"Km\" of approximately 10(-5)M) and low (\"Km\" of approximately 5 X 10(-4)M) affinity component. The high affinity component was inhibited by semicarbazide and the low affinity component by clorgyline. In the presence of 10(-3)M clorgyline, the high affinity component showed substrate inhibition at higher substrate concentrations. The possibility is discussed that the clorgyline-resistant activity is due to an amine-oxidizing activity distinct from mitochondrial MAO."}
{"id": "PMID:241806", "title": "Enhancement of permeability of ethyl cellulose films for drug penetration.", "content": "Permeability constants of salicylic acid, caffeine and benzoic acid have been measured at 37 degrees for heterogeneous films of ethyl cellulose containing up to 50% PEG 4000, the latter component undergoing leaching out. For the first two compounds, steady state constants were independent of film thickness and solute concentration but increased linearly and sharply with PEG content and were reproducible. The films were impermeable to NaOH and permeation rates were independent of receiver compartment pH. Solubility coefficients and diffusion coefficients of the substances in the films were measured using sorption and/or time lag methods and were low as compared with polyethylene films. High solubility seemed to be associated with the presence of a free activated hydrogen, shown by sorption studies on other substances. From the evidence, it appeared that mass transfer was controlled by the solubility diffusion process in the ethyl cellulose of the membranes with all three substances. Enhancement of permeability by PEG thus seemed due to increased porosity, equivalent to reduction in the effective thickness of the matrix, which nevertheless retained its barrier properties. Enhancement coefficients calculated from the slopes of PEG concentration plots may be useful for predicting the increased mass transfer of drugs through such membranes and could enable the porosity and thickness factors to be balanced against each other for formulation of coated products.", "contents": "Enhancement of permeability of ethyl cellulose films for drug penetration. Permeability constants of salicylic acid, caffeine and benzoic acid have been measured at 37 degrees for heterogeneous films of ethyl cellulose containing up to 50% PEG 4000, the latter component undergoing leaching out. For the first two compounds, steady state constants were independent of film thickness and solute concentration but increased linearly and sharply with PEG content and were reproducible. The films were impermeable to NaOH and permeation rates were independent of receiver compartment pH. Solubility coefficients and diffusion coefficients of the substances in the films were measured using sorption and/or time lag methods and were low as compared with polyethylene films. High solubility seemed to be associated with the presence of a free activated hydrogen, shown by sorption studies on other substances. From the evidence, it appeared that mass transfer was controlled by the solubility diffusion process in the ethyl cellulose of the membranes with all three substances. Enhancement of permeability by PEG thus seemed due to increased porosity, equivalent to reduction in the effective thickness of the matrix, which nevertheless retained its barrier properties. Enhancement coefficients calculated from the slopes of PEG concentration plots may be useful for predicting the increased mass transfer of drugs through such membranes and could enable the porosity and thickness factors to be balanced against each other for formulation of coated products."}
{"id": "PMID:241807", "title": "Some relations between dissolution rates and physical parameters of a drug in aqueous micellar solutions of a non-ionic surfactant.", "content": "Dissolution rates of salicylic acid from a constant surface area into a series of aqueous micellar polysorbate 20 solutions at pH 1-0 to 4-0 have been measured using two different methods; a stirred beaker and a rotating disc technique. The micellar molecular weight of polysorbate 20 has been obtained from light scattering and differential refractometry data and used with other independently determined physical data to calculate diffusion coefficients of the diffusing species. Linear multiple regression analysis was used to assess the dependence of drug dissolution rate on the diffusion coefficient and the viscosity of the dissolution medium.", "contents": "Some relations between dissolution rates and physical parameters of a drug in aqueous micellar solutions of a non-ionic surfactant. Dissolution rates of salicylic acid from a constant surface area into a series of aqueous micellar polysorbate 20 solutions at pH 1-0 to 4-0 have been measured using two different methods; a stirred beaker and a rotating disc technique. The micellar molecular weight of polysorbate 20 has been obtained from light scattering and differential refractometry data and used with other independently determined physical data to calculate diffusion coefficients of the diffusing species. Linear multiple regression analysis was used to assess the dependence of drug dissolution rate on the diffusion coefficient and the viscosity of the dissolution medium."}
{"id": "PMID:241808", "title": "The effect of ageing on the rheological properties of gelatin gels.", "content": "The effect of ageing at 4 degrees on the viscoelastic properties of 1-5 and 2-0% acid and alkaline processed gelatin gels has been investigated. Viscoelastic properties were not markedly affected by ageing time although evidence of a decrease in gel structure with increasing ageing time was apparent. This has been tentatively attributed to hydrolysis of amide links. 1-5% alkaline gels were shown to be more rigid than the corresponding acid gels and this has been discussed in terms of differences in molecular weight, polydispersity, charge and charge distribution.", "contents": "The effect of ageing on the rheological properties of gelatin gels. The effect of ageing at 4 degrees on the viscoelastic properties of 1-5 and 2-0% acid and alkaline processed gelatin gels has been investigated. Viscoelastic properties were not markedly affected by ageing time although evidence of a decrease in gel structure with increasing ageing time was apparent. This has been tentatively attributed to hydrolysis of amide links. 1-5% alkaline gels were shown to be more rigid than the corresponding acid gels and this has been discussed in terms of differences in molecular weight, polydispersity, charge and charge distribution."}
{"id": "PMID:241809", "title": "The metabolism of dibenzylamine: identification of NN-dibenzylhydroxylamine as the major in vitro metabolic product from rabbit fortified hepatic homogenates.", "content": "A study of the in vitro metabolism of dibenzylamine with fortified rabbit liver 9000 g supernatant fractions has shown that N-oxidation is the major metabolic process. Of the total amount of dibenzylamine metabolized, 90% is converted to NN-dibenzylhydroxylamine. The primary amine, benzylamine, is formed to the extent of only 6% of total substrate metabolized. The identity of the major metabolite, NN-dibenzylhydroxylamine has been established by thin-layer chromatography, gas-liquid chromatography and combined gas-liquid chromatography-mass spectrometry.", "contents": "The metabolism of dibenzylamine: identification of NN-dibenzylhydroxylamine as the major in vitro metabolic product from rabbit fortified hepatic homogenates. A study of the in vitro metabolism of dibenzylamine with fortified rabbit liver 9000 g supernatant fractions has shown that N-oxidation is the major metabolic process. Of the total amount of dibenzylamine metabolized, 90% is converted to NN-dibenzylhydroxylamine. The primary amine, benzylamine, is formed to the extent of only 6% of total substrate metabolized. The identity of the major metabolite, NN-dibenzylhydroxylamine has been established by thin-layer chromatography, gas-liquid chromatography and combined gas-liquid chromatography-mass spectrometry."}
{"id": "PMID:241810", "title": "Locomotor activity stimulation in rats produced by dopamine in the nucleus accumbens: potentiation by caffeine.", "content": "The increased motor activity of reserpine-nialamide pretreated rats given dopamine into the nucleus accumbens was potentiated in a dose-dependent manner by systemically administered caffeine. Similarly, the increase in motor activity seen when the endogenous dopamine was released by intraperitoneally administered amphetamine was potentiated by systemically given caffeine. These effects might be due to an increase in the dopamine-induced accumulation of cyclic AMP in the nucleus accumbens after inhibition of the phosphodiesterase by caffeine.", "contents": "Locomotor activity stimulation in rats produced by dopamine in the nucleus accumbens: potentiation by caffeine. The increased motor activity of reserpine-nialamide pretreated rats given dopamine into the nucleus accumbens was potentiated in a dose-dependent manner by systemically administered caffeine. Similarly, the increase in motor activity seen when the endogenous dopamine was released by intraperitoneally administered amphetamine was potentiated by systemically given caffeine. These effects might be due to an increase in the dopamine-induced accumulation of cyclic AMP in the nucleus accumbens after inhibition of the phosphodiesterase by caffeine."}
{"id": "PMID:241811", "title": "Tyrosine hydroxylase activity in rat brain regions after chronic treatment with +/--propranolol.", "content": "Rats were injected twice daily with +/--propranolol (6 mg kg-1 day-1) for 14 days and killed 16 h after the final injection. Tyrosine hydroxylase activity was measured in both soluble and particle-bound forms in various brain regions. The activity of the soluble enzyme was not significantly altered by propranolol treatment in any of the brain regions studied. The tyrosine hydroxylase activity in the particulate fraction was significantly increased in corpus striatum and unchanged in other brain regions. The propranolol concentrations in the various brain regions in this chronic study were far lower than necessary to produce a significant change in tyrosine hydroxylase activity in acute experiments. It was concluded that chronic propranolol treatment produces a persistent increase in bound tyrosine hydroxylase activity in rat corpus striatum.", "contents": "Tyrosine hydroxylase activity in rat brain regions after chronic treatment with +/--propranolol. Rats were injected twice daily with +/--propranolol (6 mg kg-1 day-1) for 14 days and killed 16 h after the final injection. Tyrosine hydroxylase activity was measured in both soluble and particle-bound forms in various brain regions. The activity of the soluble enzyme was not significantly altered by propranolol treatment in any of the brain regions studied. The tyrosine hydroxylase activity in the particulate fraction was significantly increased in corpus striatum and unchanged in other brain regions. The propranolol concentrations in the various brain regions in this chronic study were far lower than necessary to produce a significant change in tyrosine hydroxylase activity in acute experiments. It was concluded that chronic propranolol treatment produces a persistent increase in bound tyrosine hydroxylase activity in rat corpus striatum."}
{"id": "PMID:241812", "title": "Oxotremorine- and atropine-induced changes of dopamine metabolism in the rat striatum.", "content": "The effects of various doses of oxotremorine and of atropine (30 min, i.p.) on the metabolism of dopamine were examined in the striatum of the rat. Changes in striatal dopamine metabolism were estimated by following either the accumulation of [3H] dopamine 15 min after intravenous injection of [3H] tyrosine or the accumulation of dopa (taken as an index of dopamine synthesis) in animals pretreated with a dopa decarboxylase inhibitor Ro4-4602. Oxotremorine, 0-1 mg kg-1, and atropine, 1 mg kg-1, did not affect dopamine metabolism. Oxotremorine, 0-5 and 1-5 mg kg-1, did not modify dopamine concentrations but increased the accumulation of [3H]dopamine. The drug enhanced dopa formation in animals pretreated with Ro4-4602. Atropine, 5 and 20 mg kg-1, increased the accumulation of [3H]dopamine but did not affect dopamine concentrations. The accumulation of dopa was not modified there being no difference from the saline value in animals pretreated with the dopa decarboxylase inhibitor at high dopamine metabolism and atropine reduced dopamine utilization.", "contents": "Oxotremorine- and atropine-induced changes of dopamine metabolism in the rat striatum. The effects of various doses of oxotremorine and of atropine (30 min, i.p.) on the metabolism of dopamine were examined in the striatum of the rat. Changes in striatal dopamine metabolism were estimated by following either the accumulation of [3H] dopamine 15 min after intravenous injection of [3H] tyrosine or the accumulation of dopa (taken as an index of dopamine synthesis) in animals pretreated with a dopa decarboxylase inhibitor Ro4-4602. Oxotremorine, 0-1 mg kg-1, and atropine, 1 mg kg-1, did not affect dopamine metabolism. Oxotremorine, 0-5 and 1-5 mg kg-1, did not modify dopamine concentrations but increased the accumulation of [3H]dopamine. The drug enhanced dopa formation in animals pretreated with Ro4-4602. Atropine, 5 and 20 mg kg-1, increased the accumulation of [3H]dopamine but did not affect dopamine concentrations. The accumulation of dopa was not modified there being no difference from the saline value in animals pretreated with the dopa decarboxylase inhibitor at high dopamine metabolism and atropine reduced dopamine utilization."}
{"id": "PMID:241826", "title": "Microbial kinetics of drug action against gram-positive and gram-negative organisms. II: Effect of clindamycin on Staphylococcus aureus and Escherichia coli.", "content": "Clindamycin-affected Staphylococcus aureus cultures show biphasic steady-state generation curves. An initial (phase I) generation of the clindamycin-affected Staph. aureus is followed by an ultimate (phase II) generation at the same dose level. The phase I apparent generation rate constant is greater than the phase II apparent generation rate constant and suggests the development of resistant Staph. aureus mutants to clindamycin action after a finite period of drug-bacteria contact at any subcompletely inhibitory concentration level. It is rationalized that the increased resistance to drug action in mutant strains is due to a comparatively reduced ribosomal binding affinity for clindamycin. In contrast, clindamycin-affected Escherichia coli cultures show monophasic steady-state generation curves at all concentration levels; E. coli cultures do not develop resistance to clindamycin action. The dependence of the apparent generation rate constant on drug concentration yields a sigmoidal curve, which is coincident by a potency factor for the phase I and phase II generations of clindamycin-affected Staph. aureus and suggests a common mechanism of action for both generation phases. That of clindamycin-affected E. coli yields an asymptote curve, which indicates a different mechanism of action. Clindamycin possesses both a bacteriostatic and a bactericidal action on initial and mutant resistant strains of Staph. aureus, whereas its action on E. coli is only bacteriostatic. Consequently, clindamycin has a minimum inhibitory concentration (MIC) against E. coli that is about 1000 times the MIC value against Staph. aureus at 37.5 degrees. The effect of pH changes in broth media on generation inhibition of both Staph. aureus and E. coli by clindamycin action indicates that the unprotonated fraction of drug concentration contributes to the activity, possibly because of its ready penetration through cell membranes.", "contents": "Microbial kinetics of drug action against gram-positive and gram-negative organisms. II: Effect of clindamycin on Staphylococcus aureus and Escherichia coli. Clindamycin-affected Staphylococcus aureus cultures show biphasic steady-state generation curves. An initial (phase I) generation of the clindamycin-affected Staph. aureus is followed by an ultimate (phase II) generation at the same dose level. The phase I apparent generation rate constant is greater than the phase II apparent generation rate constant and suggests the development of resistant Staph. aureus mutants to clindamycin action after a finite period of drug-bacteria contact at any subcompletely inhibitory concentration level. It is rationalized that the increased resistance to drug action in mutant strains is due to a comparatively reduced ribosomal binding affinity for clindamycin. In contrast, clindamycin-affected Escherichia coli cultures show monophasic steady-state generation curves at all concentration levels; E. coli cultures do not develop resistance to clindamycin action. The dependence of the apparent generation rate constant on drug concentration yields a sigmoidal curve, which is coincident by a potency factor for the phase I and phase II generations of clindamycin-affected Staph. aureus and suggests a common mechanism of action for both generation phases. That of clindamycin-affected E. coli yields an asymptote curve, which indicates a different mechanism of action. Clindamycin possesses both a bacteriostatic and a bactericidal action on initial and mutant resistant strains of Staph. aureus, whereas its action on E. coli is only bacteriostatic. Consequently, clindamycin has a minimum inhibitory concentration (MIC) against E. coli that is about 1000 times the MIC value against Staph. aureus at 37.5 degrees. The effect of pH changes in broth media on generation inhibition of both Staph. aureus and E. coli by clindamycin action indicates that the unprotonated fraction of drug concentration contributes to the activity, possibly because of its ready penetration through cell membranes."}
{"id": "PMID:241827", "title": "Effect of pKb on lipophilic binding of disopyramide derivatives to human plasma.", "content": "The extent of plasma binding, the partition coefficient, and the pKb of 13 disopyramide derivatives were determined. The structural variation on the diisopropylaminoethyl group of disopyramide molecules influenced these physical parameters to varying degrees. Results demonstrated that the extent of interaction between drugs and human plasma was a linear function of their lipophilicity and inversely proportional to the magnitude of the pKb value.", "contents": "Effect of pKb on lipophilic binding of disopyramide derivatives to human plasma. The extent of plasma binding, the partition coefficient, and the pKb of 13 disopyramide derivatives were determined. The structural variation on the diisopropylaminoethyl group of disopyramide molecules influenced these physical parameters to varying degrees. Results demonstrated that the extent of interaction between drugs and human plasma was a linear function of their lipophilicity and inversely proportional to the magnitude of the pKb value."}
{"id": "PMID:241828", "title": "Photolytic degradation of alpha-[(dibutylamino)methyl]-6,8-dichloro-2-(3',4'-dichlorophenyl)-4-quinoline methanol: an experimental antimalarial.", "content": "A study of the effects of various storage conditions on the rate and products of degradation of the quinoline methanol antimalarial agent, alpha-[(dibutylamino)methyl]-6,8-dichloro-2-(3',4'-dichlorophenyl)-4-quinoline methanol, was undertaken. The degradation was followed by high-pressure liquid chromatography and TLC in oxygenated and deoxygenated methanol, ethanol, chloroform, and chloroform-heptane mixtures under UV and laboratory fluorescent lighting irradiation, as well as in the absence of light. The kinetics of degradation confirmed the major catalyzing factor to be UV irradiation. The compound was stable in the absence of light and reasonably stable under fluorescent lighting both in the presence and absence of oxygen. The degradation resulted in a major product, 6,8-dichloro-2-(3',4'-dichlorophenyl)-4-quinoline-carboxaldehyde, whose structure was confirmed by elemental analysis and IR, NMR, and mass spectral data.", "contents": "Photolytic degradation of alpha-[(dibutylamino)methyl]-6,8-dichloro-2-(3',4'-dichlorophenyl)-4-quinoline methanol: an experimental antimalarial. A study of the effects of various storage conditions on the rate and products of degradation of the quinoline methanol antimalarial agent, alpha-[(dibutylamino)methyl]-6,8-dichloro-2-(3',4'-dichlorophenyl)-4-quinoline methanol, was undertaken. The degradation was followed by high-pressure liquid chromatography and TLC in oxygenated and deoxygenated methanol, ethanol, chloroform, and chloroform-heptane mixtures under UV and laboratory fluorescent lighting irradiation, as well as in the absence of light. The kinetics of degradation confirmed the major catalyzing factor to be UV irradiation. The compound was stable in the absence of light and reasonably stable under fluorescent lighting both in the presence and absence of oxygen. The degradation resulted in a major product, 6,8-dichloro-2-(3',4'-dichlorophenyl)-4-quinoline-carboxaldehyde, whose structure was confirmed by elemental analysis and IR, NMR, and mass spectral data."}
{"id": "PMID:241829", "title": "GLC determination of plasma drug levels after oral administration of clorazepate potassium salts.", "content": "Plasma nordiazepam levels resulting from the oral administration of clorazepate potassium salts were determined by a sensitive GLC assay. Nordiazepam and the internal standard (diazepam) were selectively extracted into ether at pH 9.2, hydrolyzed to their respective benzophenones, and quantified by electron-capture detection. The assay was used in a comparative bioavailability study of single equimolar oral doses of monopotassium and dipotassium salts of clorazepate in dogs. Both clorazepate salts were rapidly absorbed and exhibited mean peak total drug levels after 1 hr. Clorazepate levels accounted for about 50% of the total drug levels present. No statistical difference in the plasma drug levels of clorazepate mono- and dipotassium salts and the metabolite was found in dogs.", "contents": "GLC determination of plasma drug levels after oral administration of clorazepate potassium salts. Plasma nordiazepam levels resulting from the oral administration of clorazepate potassium salts were determined by a sensitive GLC assay. Nordiazepam and the internal standard (diazepam) were selectively extracted into ether at pH 9.2, hydrolyzed to their respective benzophenones, and quantified by electron-capture detection. The assay was used in a comparative bioavailability study of single equimolar oral doses of monopotassium and dipotassium salts of clorazepate in dogs. Both clorazepate salts were rapidly absorbed and exhibited mean peak total drug levels after 1 hr. Clorazepate levels accounted for about 50% of the total drug levels present. No statistical difference in the plasma drug levels of clorazepate mono- and dipotassium salts and the metabolite was found in dogs."}
{"id": "PMID:241830", "title": "Dissolution studies with a multichannel continuous-flow apparatus.", "content": "A multichannel continuous-flow apparatus for dissolution rate measurements is described. Typical data are presented to demonstrate its utility for studies with bulk drug powders as well as with tablets and capsules without any change of setup. Procedures are given for the preparation of powder samples for dissolution studies and for a simple method of changing pH for \"retard\" tablets. The precision in dissolution rates obtained with this apparatus and method is 1-10% mean RSD. The advantages of the method are flexibility, reproducibility, and ability to obtain data in integral or differential form.", "contents": "Dissolution studies with a multichannel continuous-flow apparatus. A multichannel continuous-flow apparatus for dissolution rate measurements is described. Typical data are presented to demonstrate its utility for studies with bulk drug powders as well as with tablets and capsules without any change of setup. Procedures are given for the preparation of powder samples for dissolution studies and for a simple method of changing pH for \"retard\" tablets. The precision in dissolution rates obtained with this apparatus and method is 1-10% mean RSD. The advantages of the method are flexibility, reproducibility, and ability to obtain data in integral or differential form."}
{"id": "PMID:241831", "title": "Activity of local anesthetic agents in goldfish.", "content": "The activity of procaine hydrochloride, lidocaine hydrochloride, tetracaine hydrochloride, and dibucaine hydrochloride in producing overturn in goldfish was measured in pH 8.0 buffer. Calculation of the apparent minimum effective concentration of local anesthetic necessary to result in overturn of the goldfish showed that the activity of these agents increased in the following order: procaine hydrochloride less than lidocaine hydrochloride less than tetracaine hydrochloride less than dibucaine hydrochloride. The effect of these agents on goldfish can be correlated with previous work on the minimum concentration necessary to block conduction in isolated nerve and muscle fibers. The activity of the local anesthetic agents could be explained, in part, by the relationship between the chloroform-pH 8 buffer partition coefficient and the minimum effective concentration in goldfish. Experimental results indicate that the unionized drug molecule is responsible for the observed effects.", "contents": "Activity of local anesthetic agents in goldfish. The activity of procaine hydrochloride, lidocaine hydrochloride, tetracaine hydrochloride, and dibucaine hydrochloride in producing overturn in goldfish was measured in pH 8.0 buffer. Calculation of the apparent minimum effective concentration of local anesthetic necessary to result in overturn of the goldfish showed that the activity of these agents increased in the following order: procaine hydrochloride less than lidocaine hydrochloride less than tetracaine hydrochloride less than dibucaine hydrochloride. The effect of these agents on goldfish can be correlated with previous work on the minimum concentration necessary to block conduction in isolated nerve and muscle fibers. The activity of the local anesthetic agents could be explained, in part, by the relationship between the chloroform-pH 8 buffer partition coefficient and the minimum effective concentration in goldfish. Experimental results indicate that the unionized drug molecule is responsible for the observed effects."}
{"id": "PMID:241832", "title": "Intestinal pH as a factor in selection of animal models for bioavailability testing.", "content": "Previous in situ studies showed that intestinal drug absorption is strongly influenced by intestinal pH. Three animal species considered for bioavailability testing were studied in situ to determine intestinal pH. Results from the rat and dog correlated well with results in humans, while results from the rabbit did not. The rabbit appears to be a poor candidate for attempted animal-human bioavailability correlations.", "contents": "Intestinal pH as a factor in selection of animal models for bioavailability testing. Previous in situ studies showed that intestinal drug absorption is strongly influenced by intestinal pH. Three animal species considered for bioavailability testing were studied in situ to determine intestinal pH. Results from the rat and dog correlated well with results in humans, while results from the rabbit did not. The rabbit appears to be a poor candidate for attempted animal-human bioavailability correlations."}
{"id": "PMID:241834", "title": "Effects of normal alcohols on intestinal absorption of salicylic acid, sulfapyridine, and prednisolone in rats.", "content": "The rates of intestinal absorption of salicyclic acid, sulfapyridine, and prednisolone from solutions containing no alcohol or 0.5% ethanol, n-butanol, or n-hexanol were determined. At the concentrations used, ethanol did not significantly affect drug absorption. Butanol reduced the rate of absorption of sulfapyridine but did not significantly affect the absorption rates of prednisolone or salicylic acid. Hexanol reduced the rates of absorption of sulfapyridine and salicylic acid and increased the rate of absorption of prednisolone. The absorption-altering effects of the alcohols were concentration dependent and rapidly reversible. Histological studies indicated that the structure of the epithelium was not altered by the alcohols. While the absorption rate of water from the drug solutions was increased by the alcohols, their absorption-altering effects could not be attributed solely to increased water flux. In addition, the absorption-altering effects of the alcohols could not be attributed to formation of drug-alcohol complexes nor to alcohol-induced alterations in the extent of binding of the drugs to nondialyzable materials in the intestinal drug solution.", "contents": "Effects of normal alcohols on intestinal absorption of salicylic acid, sulfapyridine, and prednisolone in rats. The rates of intestinal absorption of salicyclic acid, sulfapyridine, and prednisolone from solutions containing no alcohol or 0.5% ethanol, n-butanol, or n-hexanol were determined. At the concentrations used, ethanol did not significantly affect drug absorption. Butanol reduced the rate of absorption of sulfapyridine but did not significantly affect the absorption rates of prednisolone or salicylic acid. Hexanol reduced the rates of absorption of sulfapyridine and salicylic acid and increased the rate of absorption of prednisolone. The absorption-altering effects of the alcohols were concentration dependent and rapidly reversible. Histological studies indicated that the structure of the epithelium was not altered by the alcohols. While the absorption rate of water from the drug solutions was increased by the alcohols, their absorption-altering effects could not be attributed solely to increased water flux. In addition, the absorption-altering effects of the alcohols could not be attributed to formation of drug-alcohol complexes nor to alcohol-induced alterations in the extent of binding of the drugs to nondialyzable materials in the intestinal drug solution."}
{"id": "PMID:241835", "title": "High-speed liquid chromatographic analysis of sulfasalazine (salicylazosulfapyridine).", "content": "A high-speed liquid chromatographic method for analysis of sulfasalazine (salicylazosulfapyridine) in bulk powder and tablet dosage form is presented. Analysis is accomplished with a reverse-phase partition column and 10% 2-propanol in pH 7.7 phosphate buffer as the mobile phase. The method of analysis utilizes a simple, one-step, solubilization procedure with dimethylformamide, addition of an internal standard, and chromatography. The method is specific for sulfasalazine in the presence of starting materials, degradation products, or by-products from its manufacture.", "contents": "High-speed liquid chromatographic analysis of sulfasalazine (salicylazosulfapyridine). A high-speed liquid chromatographic method for analysis of sulfasalazine (salicylazosulfapyridine) in bulk powder and tablet dosage form is presented. Analysis is accomplished with a reverse-phase partition column and 10% 2-propanol in pH 7.7 phosphate buffer as the mobile phase. The method of analysis utilizes a simple, one-step, solubilization procedure with dimethylformamide, addition of an internal standard, and chromatography. The method is specific for sulfasalazine in the presence of starting materials, degradation products, or by-products from its manufacture."}
{"id": "PMID:241836", "title": "CO2 retention as a basis for increased toxicity of salicylate with acetazolamide: avoidance of increased toxicity with benzolamide.", "content": "Two carbonic anhydrase inhibitors, acetazolamide and benzolamide, are capable of increasing the toxicity of sodium salicylate in mice. Beginning at about 2 mg/kg, each of the inhibitors, in combination with a fixed (400 mg/kg) dose of salicylate, generates a dose-mortality curve that reaches a plateau at about 60% deaths at 6 to 8 mg/kg. This effect can be duplicated by 8 to 10% inspired CO2. It appears that the respiratory acidosis secondary to the inhibition of red cell carbonic anhydrase is responsible for the increased toxicity; earlier work by others shows that acidosis increases the concentration of salicylate in the brain. In the treatment of salicylate poisoning by carbonic anhydrase inhibitors, the goal is to alkalinize the urine and increase the excretion of salicylate. With the newer inhibitor, benzolamide, it is possible to dissociate the respiratory acidosis from the renal effect. Maximal alkalinization of the urine is possible with a dose (about 1 mg/kg) below that which generates a respiratory acidosis. With this dose, there is no increase in the early toxicity of salicylate.", "contents": "CO2 retention as a basis for increased toxicity of salicylate with acetazolamide: avoidance of increased toxicity with benzolamide. Two carbonic anhydrase inhibitors, acetazolamide and benzolamide, are capable of increasing the toxicity of sodium salicylate in mice. Beginning at about 2 mg/kg, each of the inhibitors, in combination with a fixed (400 mg/kg) dose of salicylate, generates a dose-mortality curve that reaches a plateau at about 60% deaths at 6 to 8 mg/kg. This effect can be duplicated by 8 to 10% inspired CO2. It appears that the respiratory acidosis secondary to the inhibition of red cell carbonic anhydrase is responsible for the increased toxicity; earlier work by others shows that acidosis increases the concentration of salicylate in the brain. In the treatment of salicylate poisoning by carbonic anhydrase inhibitors, the goal is to alkalinize the urine and increase the excretion of salicylate. With the newer inhibitor, benzolamide, it is possible to dissociate the respiratory acidosis from the renal effect. Maximal alkalinization of the urine is possible with a dose (about 1 mg/kg) below that which generates a respiratory acidosis. With this dose, there is no increase in the early toxicity of salicylate."}
{"id": "PMID:241837", "title": "Antagonism of deslanoside-induced cardiotoxicity by combined nicotinic and muscarinic blockade of autonomic ganglia.", "content": "The effect of ganglionic blockade on cardiotoxicity induced by deslanoside (25 mug/kg i.v. at 15-minute intervals) was evaluated in Dial-urethane anesthetized cats. Electrocardiogram, blood pressure and pre- and postganglionic cardiac sympathetic nerve recordings were monitored. When deslanoside was given to control animals, 150 +/- 8.2 and 179 +/- 11.9 mug/kg produced ventricular tachycardia and ventricular fibrillation, respectively. Pretreatment of cats with either hexamethonium or atropine alone did not influence the doses of deslanoside required to produce ventricular tachycardia or ventricular fibrillation. However, pretreatment with the combination of hexamethonium and atropine significantly increased the dose of deslanoside needed to produce ventricular tachycardia (181 +/- 12.3 mug/kg) and ventricular fibrillation (219 +/- 12.3 mug/kg). Furthermore, administration of atropine to hexamethonium-pretreated cats intoxicated with deslanoside decreased deslanoside-induced postganglionic nerve activity. These results indicate that blockade of both nicotinic and muscarinic ganglionic transmission is essential for a protective influence against cardiotoxicity induced by deslanoside.", "contents": "Antagonism of deslanoside-induced cardiotoxicity by combined nicotinic and muscarinic blockade of autonomic ganglia. The effect of ganglionic blockade on cardiotoxicity induced by deslanoside (25 mug/kg i.v. at 15-minute intervals) was evaluated in Dial-urethane anesthetized cats. Electrocardiogram, blood pressure and pre- and postganglionic cardiac sympathetic nerve recordings were monitored. When deslanoside was given to control animals, 150 +/- 8.2 and 179 +/- 11.9 mug/kg produced ventricular tachycardia and ventricular fibrillation, respectively. Pretreatment of cats with either hexamethonium or atropine alone did not influence the doses of deslanoside required to produce ventricular tachycardia or ventricular fibrillation. However, pretreatment with the combination of hexamethonium and atropine significantly increased the dose of deslanoside needed to produce ventricular tachycardia (181 +/- 12.3 mug/kg) and ventricular fibrillation (219 +/- 12.3 mug/kg). Furthermore, administration of atropine to hexamethonium-pretreated cats intoxicated with deslanoside decreased deslanoside-induced postganglionic nerve activity. These results indicate that blockade of both nicotinic and muscarinic ganglionic transmission is essential for a protective influence against cardiotoxicity induced by deslanoside."}
{"id": "PMID:241838", "title": "Characterization of the angiotensin receptor in guinea-pig aorta.", "content": "The binding of 14C-angiotensin to the subcellular fractions of guinea-pig aorta was compared to the known physiological data as obtained from the intact preparation. Results show that only the plasma membrane fraction possesses binding characteristics consistent with the physiological data. Equilibrium of specific binding occurs at 10(-7) M 14C-angiotensin which is the physiological maximal dose. This equilibrium is achieved after 3 minutes of incubation, the time required to develop maximal response. 8-Leu-angiotensin, a specific competitive antagonist of angiotensin, blocks the binding of 14C-angiotensin in a manner similar to nonradioactive angiotensin. Neither bradykinin nor angiotensin I has a significant effect on the binding of 14C-angiotensin to plasma membranes. The dissociation constant (Ka) as calculated from the 50% inhibition of the specific binding is 2.2 X 10(-8) M. This value corresponds to the apparent Ka estimated from both the physiological dose-response curve (6.3 X 10(-8) M) and the reversibility of binding curve (4.7 X 10(-8) M). Specific binding of 14C-angiotensin is pH dependent with maximal binding occurring at pH 7.4. The rate of dissociation of 14C-angiotensin bound to plasma membranes is compatible with the recovery of the physiological response. These results indicate that the angiotensin receptor is located in the cell membrane.", "contents": "Characterization of the angiotensin receptor in guinea-pig aorta. The binding of 14C-angiotensin to the subcellular fractions of guinea-pig aorta was compared to the known physiological data as obtained from the intact preparation. Results show that only the plasma membrane fraction possesses binding characteristics consistent with the physiological data. Equilibrium of specific binding occurs at 10(-7) M 14C-angiotensin which is the physiological maximal dose. This equilibrium is achieved after 3 minutes of incubation, the time required to develop maximal response. 8-Leu-angiotensin, a specific competitive antagonist of angiotensin, blocks the binding of 14C-angiotensin in a manner similar to nonradioactive angiotensin. Neither bradykinin nor angiotensin I has a significant effect on the binding of 14C-angiotensin to plasma membranes. The dissociation constant (Ka) as calculated from the 50% inhibition of the specific binding is 2.2 X 10(-8) M. This value corresponds to the apparent Ka estimated from both the physiological dose-response curve (6.3 X 10(-8) M) and the reversibility of binding curve (4.7 X 10(-8) M). Specific binding of 14C-angiotensin is pH dependent with maximal binding occurring at pH 7.4. The rate of dissociation of 14C-angiotensin bound to plasma membranes is compatible with the recovery of the physiological response. These results indicate that the angiotensin receptor is located in the cell membrane."}
{"id": "PMID:241839", "title": "Histamine receptors in adipose tissue: involvement of cyclic adenosine monophosphate and the H2-receptor in the lipolytic response to histamine in isolated canine fat cells.", "content": "The effects of histamine on lipolysis and associated changes in adenosine 3',5'-monophosphate (cyclic AMP) levels were examined in the isolated canine fat cell. Histamine, like norepinephrine, caused a dose-dependent increase in free fatty acid (FFA) and glycerol levels. The lipolytic response to histamine was preceded by a rise in the levels of cyclic AMP and was greatly potentiated by the addition of theophylline. In isolated canine fat cells, histamine (2 muM) caused a 7-fold increase in FFA levels. This effect was inhibited more than 50% in the presence of insulin (0.4 mmu/ml) or prostaglandin E1 (2.8 muM). In similar experiments, cyclic AMP Levels were increased 11-fold by histamine (2 muM) in the presence of 1 mM theophylline. Burimamide (0.1 mM), a histamine H2-receptor antagonist, reduced the effect of histamine (2 muM) on FFA levels as well as the effect on cyclic AMP levels greater than 95% but did not inhibit the lipolytic response to norepinephrine (2 muM). Propranolol (0.01 mM), a beta adrenergic antagonist, reduced the lipolytic response to norepinephrine by 97% but did not inhibit the effects of histamine on FFA or cyclic AMP levels. Tripelennamine and 1,5-diphenyl-3-dimethylaminopyrrolidine, histamine H1-receptor antagonists, inhibited neither the lipolytic response to histamine nor the effect on cyclic AMP levels. It was concluded that histamine induces lipolysis in canine fat cells by a mechanism involving cyclic AMP and the histamine H2-receptor.", "contents": "Histamine receptors in adipose tissue: involvement of cyclic adenosine monophosphate and the H2-receptor in the lipolytic response to histamine in isolated canine fat cells. The effects of histamine on lipolysis and associated changes in adenosine 3',5'-monophosphate (cyclic AMP) levels were examined in the isolated canine fat cell. Histamine, like norepinephrine, caused a dose-dependent increase in free fatty acid (FFA) and glycerol levels. The lipolytic response to histamine was preceded by a rise in the levels of cyclic AMP and was greatly potentiated by the addition of theophylline. In isolated canine fat cells, histamine (2 muM) caused a 7-fold increase in FFA levels. This effect was inhibited more than 50% in the presence of insulin (0.4 mmu/ml) or prostaglandin E1 (2.8 muM). In similar experiments, cyclic AMP Levels were increased 11-fold by histamine (2 muM) in the presence of 1 mM theophylline. Burimamide (0.1 mM), a histamine H2-receptor antagonist, reduced the effect of histamine (2 muM) on FFA levels as well as the effect on cyclic AMP levels greater than 95% but did not inhibit the lipolytic response to norepinephrine (2 muM). Propranolol (0.01 mM), a beta adrenergic antagonist, reduced the lipolytic response to norepinephrine by 97% but did not inhibit the effects of histamine on FFA or cyclic AMP levels. Tripelennamine and 1,5-diphenyl-3-dimethylaminopyrrolidine, histamine H1-receptor antagonists, inhibited neither the lipolytic response to histamine nor the effect on cyclic AMP levels. It was concluded that histamine induces lipolysis in canine fat cells by a mechanism involving cyclic AMP and the histamine H2-receptor."}
{"id": "PMID:241840", "title": "Binding of N1-methylnicotinamide and p-aminohippuric acid to a particulate fraction from dog kidney.", "content": "The active secretion of organic ions by the kidney may be described by the following models: 1)binding to a carrier protein and 2) a translocation process across the membrane. The feasibility of such a model was tested by measuring binding of either an organic cation, N1-methylnicotinamide (NMN) or an organic anion p-aminohippuric acid (PAH) to particulate material obtained from dog renal cortex tissue. The method employed was one in which the bound and free forms of the ligand were separated by centrifugation through a gel matrix. Binding of NMN and PAH was found to be tissue specific. In addition, binding was pH, time, temperature, protein-concentration and ligand-concentration dependent. Saturation of binding for either ligand was observed at concentrations greater than 50 mM, suggesting low affinity. Interestingly, a positive cooperative effect was observed for binding of either NMN or PAH to the particulate material. Although binding was associated only with particulate material, the binding proteins were released from the membrane system(s) by treatment with the nonionic detergent Lubrol WX. These studies show that NMN and PAH binding share many features in common but that the two processes are independent of each other. The results are consistent with, but do not prove, the model.", "contents": "Binding of N1-methylnicotinamide and p-aminohippuric acid to a particulate fraction from dog kidney. The active secretion of organic ions by the kidney may be described by the following models: 1)binding to a carrier protein and 2) a translocation process across the membrane. The feasibility of such a model was tested by measuring binding of either an organic cation, N1-methylnicotinamide (NMN) or an organic anion p-aminohippuric acid (PAH) to particulate material obtained from dog renal cortex tissue. The method employed was one in which the bound and free forms of the ligand were separated by centrifugation through a gel matrix. Binding of NMN and PAH was found to be tissue specific. In addition, binding was pH, time, temperature, protein-concentration and ligand-concentration dependent. Saturation of binding for either ligand was observed at concentrations greater than 50 mM, suggesting low affinity. Interestingly, a positive cooperative effect was observed for binding of either NMN or PAH to the particulate material. Although binding was associated only with particulate material, the binding proteins were released from the membrane system(s) by treatment with the nonionic detergent Lubrol WX. These studies show that NMN and PAH binding share many features in common but that the two processes are independent of each other. The results are consistent with, but do not prove, the model."}
{"id": "PMID:241841", "title": "The influence of age on the distribution, metabolism and excretion of methoxyflurane in Fischer 344 rats: a possible relationship to nephrotoxicity.", "content": "Age as a factor in methoxyflurane nephrotoxicity was evaluated in Fischer 344 rats of various ages by determination of: 1) serum inorganic fluoride and methoxyflurane concentrations, and urinary inorganic fluoride excretion in methoxyflurane-exposed rats; 2) liver microsomal methoxyflurane defluorinase activity; and 3) distribution of injected sodium fluoride. Only rats in the youngest age group (6 weeks) did not develop nephrotoxicity after anesthesia. Older rats had a biphasic rather than a monophasic decay in serum methoxyflurane concentration and also had increased serum inorganic fluoride concentration and urinary inorganic fluoride excretion. Older rats also excreted a greater proportion of an injected dose of sodium fluoride compared to young rats. Microsomal methoxyflurane defluorinase specific activity was similar among rats of all ages. It is likely that increased availability of methoxyflurane  due to its greater storage in fat led to more inorganic fluoride production in older compared to younger rats. Bone sequestration of inorganic fluoride in younger rats probably accounts for decreased serum inorganic fluoride levels in that group. Both factors cause significant differences in renal exposure to inorganic fluoride; thus the risk of nephrotoxicity is less in younger animals.", "contents": "The influence of age on the distribution, metabolism and excretion of methoxyflurane in Fischer 344 rats: a possible relationship to nephrotoxicity. Age as a factor in methoxyflurane nephrotoxicity was evaluated in Fischer 344 rats of various ages by determination of: 1) serum inorganic fluoride and methoxyflurane concentrations, and urinary inorganic fluoride excretion in methoxyflurane-exposed rats; 2) liver microsomal methoxyflurane defluorinase activity; and 3) distribution of injected sodium fluoride. Only rats in the youngest age group (6 weeks) did not develop nephrotoxicity after anesthesia. Older rats had a biphasic rather than a monophasic decay in serum methoxyflurane concentration and also had increased serum inorganic fluoride concentration and urinary inorganic fluoride excretion. Older rats also excreted a greater proportion of an injected dose of sodium fluoride compared to young rats. Microsomal methoxyflurane defluorinase specific activity was similar among rats of all ages. It is likely that increased availability of methoxyflurane  due to its greater storage in fat led to more inorganic fluoride production in older compared to younger rats. Bone sequestration of inorganic fluoride in younger rats probably accounts for decreased serum inorganic fluoride levels in that group. Both factors cause significant differences in renal exposure to inorganic fluoride; thus the risk of nephrotoxicity is less in younger animals."}
{"id": "PMID:241842", "title": "Functional characteristics of the renal tubular secretion of amprolium, a quaternary organic base.", "content": "Amprolium [1-(4-amino-2-propyl-5-pyrimidinemethyl)-2-methyl-pyridinium chloride hydrochloridel is a basic (quaternary) organic compound. At very low plasma concentration, it is cleared by the kidney at a rate approximating renal plasma flow in the dog. Its renal clearance is not depressed by organic acids (p-aminohippurate or probenecid) but is reduced by the quaternary base, mepiperphenidol. Acetate and pantothenate may influence the clearance of amprolium but, if this is the case, the effect is less than for p-aminohippurate. Its clearance is depressed as urinary pH is increased. The clearance of amprolium was not altered over a substantial range in urine flow at either high or low urinary pH.", "contents": "Functional characteristics of the renal tubular secretion of amprolium, a quaternary organic base. Amprolium [1-(4-amino-2-propyl-5-pyrimidinemethyl)-2-methyl-pyridinium chloride hydrochloridel is a basic (quaternary) organic compound. At very low plasma concentration, it is cleared by the kidney at a rate approximating renal plasma flow in the dog. Its renal clearance is not depressed by organic acids (p-aminohippurate or probenecid) but is reduced by the quaternary base, mepiperphenidol. Acetate and pantothenate may influence the clearance of amprolium but, if this is the case, the effect is less than for p-aminohippurate. Its clearance is depressed as urinary pH is increased. The clearance of amprolium was not altered over a substantial range in urine flow at either high or low urinary pH."}
{"id": "PMID:241843", "title": "The mechanism by which methiothepin, a putative serotonin receptor antagonist, icnreses brain 5-hydroxyindole levels.", "content": "Brain tryptophan and 5-hydroxyindole levels are elevated in rats given methiothepin, a neuroleptic that appears to block serotonin receptors. The rise in brain tryptophan probably results from a drug-induced increase in the ratio of plasma tryptophan concentration to the sum of the neutral amino acids in plasma that compete with tryptophan for uptake into the brain; this change in the plasma amino acid pattern may be mediated in part by a methiothepin-induced rise in plasma insulin. Methiothepin also decreases the proportion of circulating tryptophan that is bound to albumin. Unlike exogenous tryptophan, methiothepin fails to increase 5-hydroxyin-doles caudal to the site of a spinal cord transection. Therefore, the mechanism by which methiothepin elevates 5-hydroxyindole levels involves not only increased brain tryptophan levels but also continued impulse flow along serotonergic neurons.", "contents": "The mechanism by which methiothepin, a putative serotonin receptor antagonist, icnreses brain 5-hydroxyindole levels. Brain tryptophan and 5-hydroxyindole levels are elevated in rats given methiothepin, a neuroleptic that appears to block serotonin receptors. The rise in brain tryptophan probably results from a drug-induced increase in the ratio of plasma tryptophan concentration to the sum of the neutral amino acids in plasma that compete with tryptophan for uptake into the brain; this change in the plasma amino acid pattern may be mediated in part by a methiothepin-induced rise in plasma insulin. Methiothepin also decreases the proportion of circulating tryptophan that is bound to albumin. Unlike exogenous tryptophan, methiothepin fails to increase 5-hydroxyin-doles caudal to the site of a spinal cord transection. Therefore, the mechanism by which methiothepin elevates 5-hydroxyindole levels involves not only increased brain tryptophan levels but also continued impulse flow along serotonergic neurons."}
{"id": "PMID:241844", "title": "Alpha adrenergic and histaminergic effects of tolazoline-like imidazolines.", "content": "For eliciting contraction of rabbit aorta, the relative potency of agonists in terms of negative log molar ED50 were: oxymetazoline (8.4) greater than naphazoline (7.95) greater than phenylephrine (7.31) greater than tetrahydrozoline (6.5) greater than tolazoline (5.80). None of the imidazolines, however, produced maximal effects equal to that of phenylephrine. All agonists were directly acting agents. The interactions between oxymetazoline and phentolamine or tolazoline and phentolamine were competitive with pA2 values of 8.1 and 8.0, respectively. Phentolamine with tetrahydrozoline, naphazoline or phenylephrine produced nearly equal KB values. Thus, all the agonists and alpha adrenoceptor blockers must act at a common site in rabbit aorta. As expected, the contraction of rabbit aorta produced by an imidazole histamine was competitively antagonized by the histamine 1 antagonist, chlorpheniramine (K B 7.6 X 10(-9) M). The antagonist failed to block the contraction produced by the imidazolines studied. On guinea-pig aorta, the relative potency of the agonists varied greatly. On guinea-pig atria, tetrahydrozoline and tolazoline produced positive chronotropic effects which were not influenced by reserpine and cocaine treatment, or treatment with a beta adrenoceptor blocker, propranolol. The histamine 2 receptor antagonist, metiamide, however, selectively blocked the cardiac effects. It is concluded that oxymetazoline and naphazoline do not activate histamine 1 or histamine 2 receptors or beta adrenoceptors. Thus, the drugs are highly specific alpha adrenoceptor stimulants. On the other hand, tetrahydrozoline and tolazoline interact with histamine 2 receptors and with alpha adrenoceptors, but not with histamine 1 receptors or with beta adrenoceptors.", "contents": "Alpha adrenergic and histaminergic effects of tolazoline-like imidazolines. For eliciting contraction of rabbit aorta, the relative potency of agonists in terms of negative log molar ED50 were: oxymetazoline (8.4) greater than naphazoline (7.95) greater than phenylephrine (7.31) greater than tetrahydrozoline (6.5) greater than tolazoline (5.80). None of the imidazolines, however, produced maximal effects equal to that of phenylephrine. All agonists were directly acting agents. The interactions between oxymetazoline and phentolamine or tolazoline and phentolamine were competitive with pA2 values of 8.1 and 8.0, respectively. Phentolamine with tetrahydrozoline, naphazoline or phenylephrine produced nearly equal KB values. Thus, all the agonists and alpha adrenoceptor blockers must act at a common site in rabbit aorta. As expected, the contraction of rabbit aorta produced by an imidazole histamine was competitively antagonized by the histamine 1 antagonist, chlorpheniramine (K B 7.6 X 10(-9) M). The antagonist failed to block the contraction produced by the imidazolines studied. On guinea-pig aorta, the relative potency of the agonists varied greatly. On guinea-pig atria, tetrahydrozoline and tolazoline produced positive chronotropic effects which were not influenced by reserpine and cocaine treatment, or treatment with a beta adrenoceptor blocker, propranolol. The histamine 2 receptor antagonist, metiamide, however, selectively blocked the cardiac effects. It is concluded that oxymetazoline and naphazoline do not activate histamine 1 or histamine 2 receptors or beta adrenoceptors. Thus, the drugs are highly specific alpha adrenoceptor stimulants. On the other hand, tetrahydrozoline and tolazoline interact with histamine 2 receptors and with alpha adrenoceptors, but not with histamine 1 receptors or with beta adrenoceptors."}
{"id": "PMID:241845", "title": "Gel entrapped L-asparaginase: kinetic behavior and antitumor activity.", "content": "L-Asparaginase from Escherichia coli was immobilized by entrapment in a gel based on poly(2-hydroxyethyl methacrylate) with an activity as high as 730 I.U./g of dry gel. The apparent Michaelis constant for these gels was similar to that of the free enzyme. At 37 degrees C the immobilized enzyme had a half-life of more than 40 days, in vitro. The gel was freeze-dried, crushed and sieved to pass a 38 mum screen, giving a median particle size of 12 mum. C3H mice were injected intraperitoneally with 40 I.U. of L-asparaginase; the peak plasma activity after 4 hours was only 0.9 I.U. for the gel entrapped enzyme compared to a peak activity of 5.0 I.U. after 2 hours for the native L-asparaginase. Ninety percent of the plasma enzyme activity for the gel entrapped case was sedimentable at 21,000 X g, indicating a small leakage of the enzyme from the gel; the clearance for the enzyme activity in plasma had an initial half-life of 13 hours in contrast to a half-life of 2 hours for the native preparation. After intraperitineal injection of 5.0 I.U. into C3H mice, plasma L-asparagine fell to undetectable levels for 4 days and reappeared by day 8 for both the native and immobilized enzymes. Subcutaneously transplanted 6C3HED murine lymphoma was inhibited by 35, 78 and 100% after single intraperitoneal injections of immobilized L-asparaginase of 2, 4 and 8 I.U., respectively, as compared to 36, 53 and 86% for the native enzyme by the 14th day. Body weight changes after receiving immobilized L-asparaginase were essentially similar to those of animals receiving a comparable dose of native enzyme. These results indicate that while most of the immobilized L-asparaginase remains at the injection site, it produces a significant plasma L-asparagine depression and antitumor acitivity comparable to that of the native preparation without major toxicity.", "contents": "Gel entrapped L-asparaginase: kinetic behavior and antitumor activity. L-Asparaginase from Escherichia coli was immobilized by entrapment in a gel based on poly(2-hydroxyethyl methacrylate) with an activity as high as 730 I.U./g of dry gel. The apparent Michaelis constant for these gels was similar to that of the free enzyme. At 37 degrees C the immobilized enzyme had a half-life of more than 40 days, in vitro. The gel was freeze-dried, crushed and sieved to pass a 38 mum screen, giving a median particle size of 12 mum. C3H mice were injected intraperitoneally with 40 I.U. of L-asparaginase; the peak plasma activity after 4 hours was only 0.9 I.U. for the gel entrapped enzyme compared to a peak activity of 5.0 I.U. after 2 hours for the native L-asparaginase. Ninety percent of the plasma enzyme activity for the gel entrapped case was sedimentable at 21,000 X g, indicating a small leakage of the enzyme from the gel; the clearance for the enzyme activity in plasma had an initial half-life of 13 hours in contrast to a half-life of 2 hours for the native preparation. After intraperitineal injection of 5.0 I.U. into C3H mice, plasma L-asparagine fell to undetectable levels for 4 days and reappeared by day 8 for both the native and immobilized enzymes. Subcutaneously transplanted 6C3HED murine lymphoma was inhibited by 35, 78 and 100% after single intraperitoneal injections of immobilized L-asparaginase of 2, 4 and 8 I.U., respectively, as compared to 36, 53 and 86% for the native enzyme by the 14th day. Body weight changes after receiving immobilized L-asparaginase were essentially similar to those of animals receiving a comparable dose of native enzyme. These results indicate that while most of the immobilized L-asparaginase remains at the injection site, it produces a significant plasma L-asparagine depression and antitumor acitivity comparable to that of the native preparation without major toxicity."}
{"id": "PMID:241849", "title": "Preceramic and postceramic solder joints.", "content": "This investigation evaluated preceramic and postceramic soldering procedures. Three gap spaces and two soldering methods were evaluated. Wider gaps produced stronger joints. The strongest joints were achieved by using wider gaps and the oven soldering technique. Very wide gaps (0.76 mm.) are not recommended because of possible distortion through excessive solder shrinkage. However, in practice, many solder joints exceed the 0.31 mm. recommended minimum; these joints will not show decreased strength.", "contents": "Preceramic and postceramic solder joints. This investigation evaluated preceramic and postceramic soldering procedures. Three gap spaces and two soldering methods were evaluated. Wider gaps produced stronger joints. The strongest joints were achieved by using wider gaps and the oven soldering technique. Very wide gaps (0.76 mm.) are not recommended because of possible distortion through excessive solder shrinkage. However, in practice, many solder joints exceed the 0.31 mm. recommended minimum; these joints will not show decreased strength."}
{"id": "PMID:241848", "title": "The interaction of pH and divalent cations at the neuromuscular junction.", "content": "1. 1. The effects of acidic pH on transmitter release were studied at the frog neuromuscular junction, using intracellular recording techniques. 2. Acid pH reduced the amplitude of the end-plate potentials (e.p.p.s) and accelerated the frequency of the miniature e.p.p.s(m.e.p.p.s). 3. At pH 6-0 the m.e.p.p. frequency was on the average 2-5 times greater than at pH 7-4. This multiplication was independent of the divalent ion concentration of the medium over a large range. 4. Reduction of the e.p.p. amplitude at low pH was the result of a decrease in m, the number of quanta of transmitter liberated by the nerve impulse. 5. The effect of low pH on m was blocked by high concentrations of Mg2+ and by lower concentrations of Mn2+ ions. This occlusion was found even when the total concentration of divalents in the bathing solution was kept constant. 6. These results indicated that H+ and Mn2+ ions bind to an acidic site which regulates Ca-mediated release of acetylcholine (ACh). The acid dissociation constant (KH) was determined using both a kinetic and a surface charge model. The pKa of the site calculated from the kinetic model was 5-7, while a pKa of 3-6 was obtained from the surface charge model. 7. It is suggested that protonation of the acidic site mentioned above reduces evoked transmitter release by blocking the influx of Ca into the nerve terminal following the nerve action potential.", "contents": "The interaction of pH and divalent cations at the neuromuscular junction. 1. 1. The effects of acidic pH on transmitter release were studied at the frog neuromuscular junction, using intracellular recording techniques. 2. Acid pH reduced the amplitude of the end-plate potentials (e.p.p.s) and accelerated the frequency of the miniature e.p.p.s(m.e.p.p.s). 3. At pH 6-0 the m.e.p.p. frequency was on the average 2-5 times greater than at pH 7-4. This multiplication was independent of the divalent ion concentration of the medium over a large range. 4. Reduction of the e.p.p. amplitude at low pH was the result of a decrease in m, the number of quanta of transmitter liberated by the nerve impulse. 5. The effect of low pH on m was blocked by high concentrations of Mg2+ and by lower concentrations of Mn2+ ions. This occlusion was found even when the total concentration of divalents in the bathing solution was kept constant. 6. These results indicated that H+ and Mn2+ ions bind to an acidic site which regulates Ca-mediated release of acetylcholine (ACh). The acid dissociation constant (KH) was determined using both a kinetic and a surface charge model. The pKa of the site calculated from the kinetic model was 5-7, while a pKa of 3-6 was obtained from the surface charge model. 7. It is suggested that protonation of the acidic site mentioned above reduces evoked transmitter release by blocking the influx of Ca into the nerve terminal following the nerve action potential."}
{"id": "PMID:241863", "title": "Cyanogen induced phosphorylation of D-fructose.", "content": "Cyanogen-induced phosphorylation of D-fructose at pH 8.8 led to the formation of a phosphorylated sugar identified as alpha-D-furcto-pyranose 2-phosphate on the basis of its chromatographic and electrophoretic properties, its lability to hydrolysis by alkaline phosphatase, the rate of its acid-catalysed hydrolysis, the results of periodate oxidation and optical rotatory measurements.", "contents": "Cyanogen induced phosphorylation of D-fructose. Cyanogen-induced phosphorylation of D-fructose at pH 8.8 led to the formation of a phosphorylated sugar identified as alpha-D-furcto-pyranose 2-phosphate on the basis of its chromatographic and electrophoretic properties, its lability to hydrolysis by alkaline phosphatase, the rate of its acid-catalysed hydrolysis, the results of periodate oxidation and optical rotatory measurements."}
{"id": "PMID:241864", "title": "Hormonal induction of tyrosine aminotransferase activity in host liver and hepatoma no. 7777 of normal and cofactor-depleted animals.", "content": "Induction of tyrosine aminotransferase (TAT) (EC 2.6.1.5) by hydrocortisone was studied during cofactor (pyridoxal phosphate) depletion in hepatoma-bearing BUF strain female rats. Pairs of rats were matched for weight and age and one from each pair was fed ad libitum a diet lacking pyridoxine; the other (referred to as \"pair-fed\") was given the same diet supplemented with the vitamin, with the amount restricted to that consumed by the matched animal on the deficient diet. All animals were inoculated with Morris hepatoma no. 7777 cell after 21 days on the respective diets. TAT specific activity was determined weekly in host liver and hepatoma, in the presence and absence of cofactor, before and after the administration of hydrocortisone. Free and bound pyridoxal phosphate was estimated enzymatically. The average weight of hepatomas from pair-fed animals was 1.5-fold to twofold greater than that of hepatomas from animals on deficient diets. TAT activity of hepatomas was two times greater than that of host liver, and lack of dietary pyridoxine was without effect. Hormonal induction of enzymatic activity was maximal after the first week of tumor growth and subsequently reached minimal values. In pair-fed animals, tumor TAT was approximately 60% saturated with cofactor. In vitamin-deficient animals, only 6% of the tumor enzyme was saturated with the cofactor. The percent saturation of host liver TAT varied, with minimal values found in the vitamin-deficient animals. Hepatic and tumor pyridoxal phosphate content of pair-fed animals was unusually high (10 mug/g); in vitamin-deficient animals, only the coenzyme content of hepatomas was high (7.0 mug/g). The results showed that presence of the tumor altered the a) specific activity level of TAT and tissue content of cofactor, b) pattern of hormonal induction of the enzyme, and c) effects of the absence of dietary pyridoxine on TAT induction observed in animals without tumors.", "contents": "Hormonal induction of tyrosine aminotransferase activity in host liver and hepatoma no. 7777 of normal and cofactor-depleted animals. Induction of tyrosine aminotransferase (TAT) (EC 2.6.1.5) by hydrocortisone was studied during cofactor (pyridoxal phosphate) depletion in hepatoma-bearing BUF strain female rats. Pairs of rats were matched for weight and age and one from each pair was fed ad libitum a diet lacking pyridoxine; the other (referred to as \"pair-fed\") was given the same diet supplemented with the vitamin, with the amount restricted to that consumed by the matched animal on the deficient diet. All animals were inoculated with Morris hepatoma no. 7777 cell after 21 days on the respective diets. TAT specific activity was determined weekly in host liver and hepatoma, in the presence and absence of cofactor, before and after the administration of hydrocortisone. Free and bound pyridoxal phosphate was estimated enzymatically. The average weight of hepatomas from pair-fed animals was 1.5-fold to twofold greater than that of hepatomas from animals on deficient diets. TAT activity of hepatomas was two times greater than that of host liver, and lack of dietary pyridoxine was without effect. Hormonal induction of enzymatic activity was maximal after the first week of tumor growth and subsequently reached minimal values. In pair-fed animals, tumor TAT was approximately 60% saturated with cofactor. In vitamin-deficient animals, only 6% of the tumor enzyme was saturated with the cofactor. The percent saturation of host liver TAT varied, with minimal values found in the vitamin-deficient animals. Hepatic and tumor pyridoxal phosphate content of pair-fed animals was unusually high (10 mug/g); in vitamin-deficient animals, only the coenzyme content of hepatomas was high (7.0 mug/g). The results showed that presence of the tumor altered the a) specific activity level of TAT and tissue content of cofactor, b) pattern of hormonal induction of the enzyme, and c) effects of the absence of dietary pyridoxine on TAT induction observed in animals without tumors."}
{"id": "PMID:241866", "title": "Multiple endocrine adenomatosis type IIb. Diagnosis and treatment.", "content": "A 29-year-old man with a marfanoid habitus, peculiar mucosal neuromas of the lips and tongue, high arched palate, hyperplastic corneal nerves, and hypertension was found at operation to have medullary carcinoma of the thyroid, parathyroid hyperplasia, and pheochromocytoma. These symptoms and findings are characteristic of multiple endocrine adenomatosis (MEA IIb) syndromes.", "contents": "Multiple endocrine adenomatosis type IIb. Diagnosis and treatment. A 29-year-old man with a marfanoid habitus, peculiar mucosal neuromas of the lips and tongue, high arched palate, hyperplastic corneal nerves, and hypertension was found at operation to have medullary carcinoma of the thyroid, parathyroid hyperplasia, and pheochromocytoma. These symptoms and findings are characteristic of multiple endocrine adenomatosis (MEA IIb) syndromes."}
{"id": "PMID:241868", "title": "Mass screening for sickle cell hemoglobin. Is there an optimal method?", "content": "The problem of screening large civilian and military populations for sickle cell hemoglobin and related conditions has been approached recently by three distinct methods. One method specifies hemoglobin electrophoresis as the initial screening technique, followed by a solubility (dithionite) test when a (nonspecific) \"S band\" is noted. Another method requires the use of the automated dithionite test, followed, when positive, by hemoglobin electrophoresis. A third method is a dual, automated technique for detecting anemia or hemoglobin S or both in the initial screening study; hemoglobin electrophoresis studies are done when indicated. All three methods provide data suitable for accurate diagnosis and genetic counseling, but substantial variations in costs and redundancy of data are found among these methods. Because it gives the \"biggest diagnostic bang for the buck\", the third merits widespread adoption.", "contents": "Mass screening for sickle cell hemoglobin. Is there an optimal method? The problem of screening large civilian and military populations for sickle cell hemoglobin and related conditions has been approached recently by three distinct methods. One method specifies hemoglobin electrophoresis as the initial screening technique, followed by a solubility (dithionite) test when a (nonspecific) \"S band\" is noted. Another method requires the use of the automated dithionite test, followed, when positive, by hemoglobin electrophoresis. A third method is a dual, automated technique for detecting anemia or hemoglobin S or both in the initial screening study; hemoglobin electrophoresis studies are done when indicated. All three methods provide data suitable for accurate diagnosis and genetic counseling, but substantial variations in costs and redundancy of data are found among these methods. Because it gives the \"biggest diagnostic bang for the buck\", the third merits widespread adoption."}
{"id": "PMID:241871", "title": "Blood zinc levels in patients with arteriosclerosis obliterans, thromboangiitis obliterans and Takayasu's disease.", "content": "Serum zinc concentration was measured by atomic absorption spectrophotometry in 30 normal males, 17 normal females, 20 patients with arteriosclerosis obliterans, 26 patients with thromboangiitis obliterans, 40 patients with Takayasu's disease. The mean serum zinc concentration was 93.9 +/- S.E.4.0 mug/100 ml in the normal male controls, 75.1 +/- 3.3 mug/100 ml in patients with arteriosclerosis obliterans without ulcers (P less than 0.05) and 79.2 +/- 6.5 mug/100 ml in patients with thromboangiitis obliterans without ulcers. Serum zinc concentration showed to be more decreased in patients with these diseases who had ulcers. The mean serum zinc concentration was 77.9 +/- 4.0 mug/100 ml in the normal female controls, 71.8 +/- 5.1 mug/100 ml in patients with Takayasu's disease who had never been treated with steroids and 59.1 +/- 2.7 mug/100 ml in patients with this disease who had been treated with this drug (P less than 0.01). The zinc level was significantly lower in CRP positive patients with Takayasu's disease than in CRP negative patients (P less than 0.05).", "contents": "Blood zinc levels in patients with arteriosclerosis obliterans, thromboangiitis obliterans and Takayasu's disease. Serum zinc concentration was measured by atomic absorption spectrophotometry in 30 normal males, 17 normal females, 20 patients with arteriosclerosis obliterans, 26 patients with thromboangiitis obliterans, 40 patients with Takayasu's disease. The mean serum zinc concentration was 93.9 +/- S.E.4.0 mug/100 ml in the normal male controls, 75.1 +/- 3.3 mug/100 ml in patients with arteriosclerosis obliterans without ulcers (P less than 0.05) and 79.2 +/- 6.5 mug/100 ml in patients with thromboangiitis obliterans without ulcers. Serum zinc concentration showed to be more decreased in patients with these diseases who had ulcers. The mean serum zinc concentration was 77.9 +/- 4.0 mug/100 ml in the normal female controls, 71.8 +/- 5.1 mug/100 ml in patients with Takayasu's disease who had never been treated with steroids and 59.1 +/- 2.7 mug/100 ml in patients with this disease who had been treated with this drug (P less than 0.01). The zinc level was significantly lower in CRP positive patients with Takayasu's disease than in CRP negative patients (P less than 0.05)."}
{"id": "PMID:241872", "title": "Hemodynamics of spontaneously hypertensive rats in conscious state.", "content": "Cardiac output of unanesthetized spontaneously hypertensive rats (SHR) and normotensive control rats (NCR) was measured by an aortic pressure pulse contour method. A catheter was introduced into the aortic arch under ether anesthesia and aortic pressure curves were recorded after the recovery from anesthesia. Stroke volume was calculated by reading required pressure and time data on the tracings and substituting them into a special equation. Cardiac output per min per body weight was not significantly different between SHR and NCR. Arterial pressure and total peripheral resistance were higher in SHR than in NCR. On ganglion blockade with hexamethonium bromide in the conscious state, arterial pressure decreased more markedly in SHR than in NCR. Though arterial pressure was still significantly (P less than 0.05) higher in SHR after blockade, cardiac output was larger in SHR more than to account for the difference in arterial pressure. Total peripheral resistance was lower in SHR than in NCR after blockade. It is concluded that, even in the conscious state as in the anesthetized state, the major contribution to the hypertensive state in SHR is an increase in total peripheral resistance due to an elevation of the sympathetic tone.", "contents": "Hemodynamics of spontaneously hypertensive rats in conscious state. Cardiac output of unanesthetized spontaneously hypertensive rats (SHR) and normotensive control rats (NCR) was measured by an aortic pressure pulse contour method. A catheter was introduced into the aortic arch under ether anesthesia and aortic pressure curves were recorded after the recovery from anesthesia. Stroke volume was calculated by reading required pressure and time data on the tracings and substituting them into a special equation. Cardiac output per min per body weight was not significantly different between SHR and NCR. Arterial pressure and total peripheral resistance were higher in SHR than in NCR. On ganglion blockade with hexamethonium bromide in the conscious state, arterial pressure decreased more markedly in SHR than in NCR. Though arterial pressure was still significantly (P less than 0.05) higher in SHR after blockade, cardiac output was larger in SHR more than to account for the difference in arterial pressure. Total peripheral resistance was lower in SHR than in NCR after blockade. It is concluded that, even in the conscious state as in the anesthetized state, the major contribution to the hypertensive state in SHR is an increase in total peripheral resistance due to an elevation of the sympathetic tone."}
{"id": "PMID:241873", "title": "An analysis of the drugs acting on cerebral energy metabolism.", "content": "The behaviour of (a) the redox potential of the lactate/pyruvate system and the changes of the redox potential of the lactate/pyruvate system across the brain; (b) the energy charge potential of the adenylate pool, was studied in the brain of curarized beagle dogs. The influence of certain drugs (amobarbital, nicergoline, theophylline, papaverine, bamethan, dipyridamole, bemegride) on these parameters was evaluated under control conditions, during hypoxemia and during post-hypoxiemic recovery. On the whole, the action on energetic metabolism appears to be unrelated to the action believed to be exerted by drugs on cerebral vessels.", "contents": "An analysis of the drugs acting on cerebral energy metabolism. The behaviour of (a) the redox potential of the lactate/pyruvate system and the changes of the redox potential of the lactate/pyruvate system across the brain; (b) the energy charge potential of the adenylate pool, was studied in the brain of curarized beagle dogs. The influence of certain drugs (amobarbital, nicergoline, theophylline, papaverine, bamethan, dipyridamole, bemegride) on these parameters was evaluated under control conditions, during hypoxemia and during post-hypoxiemic recovery. On the whole, the action on energetic metabolism appears to be unrelated to the action believed to be exerted by drugs on cerebral vessels."}
{"id": "PMID:241874", "title": "[Coronary reserve and differentiated therapy of its disorder].", "content": "The clinical course of the ischaemic heart disease was studied and compared with the ECG indices at rest, and under exercises, and with the data of selective coronary angiography in 189 patients. Three stages of decompensation of the coronary reserve were revealed. The efficiency of drug therapy and the indications for surgical management were studied with reference to the state of the coronary reserve.", "contents": "[Coronary reserve and differentiated therapy of its disorder]. The clinical course of the ischaemic heart disease was studied and compared with the ECG indices at rest, and under exercises, and with the data of selective coronary angiography in 189 patients. Three stages of decompensation of the coronary reserve were revealed. The efficiency of drug therapy and the indications for surgical management were studied with reference to the state of the coronary reserve."}
{"id": "PMID:241876", "title": "[Effect of chronic beta-adrenergic blockade on blood pressure and release of renin, aldosterone and cortisol in essential hypertension (author's transl)].", "content": "Blood pressure (BP), plasma renin activity (PRA) and plasma concentration of aldosterone (PA) and cortisol (PC) were determined in essential hypertensive patients before and after beta-adrenergic blockade with propranolol and prindolol. Serial measurements of PRA, PA and PC at 30 min intervals (8 p.m. to 6 a.m.) were performed in 8 patients. Administration of propranolol (50 mg three times daily) over a period of 4 weeks was followed by a significant reduction in BP, PRA and PA. PC remained unaltered. The pattern of rhythmic secretion of renin was abolished whereas that of aldosterone persisted at a lower level. Prindolol (10 mg three times daily) had a similar effect on BP as propranolol but failed to lower PRA and PA. Rhythmic secretion of renin was also markedly altered with prindolol in the absence of any change in rhythmicity of PA and PC. The hypotensive action of prindolol was not mediated via inhibition of renin release. The dissociation between PRA and PA rhythmicity indicates that during beta-adrenergic blockade diurnal rhythm of aldosterone secretion is not regulated by the renin-angiotensin-system. Rhythmicity of PC was normal, indicating that also ACTH-secretion was unaltered. Thus, under beta-blockade unchanged diurnal rhythm of aldosterone may be due to normal ACTH-secretion.", "contents": "[Effect of chronic beta-adrenergic blockade on blood pressure and release of renin, aldosterone and cortisol in essential hypertension (author's transl)]. Blood pressure (BP), plasma renin activity (PRA) and plasma concentration of aldosterone (PA) and cortisol (PC) were determined in essential hypertensive patients before and after beta-adrenergic blockade with propranolol and prindolol. Serial measurements of PRA, PA and PC at 30 min intervals (8 p.m. to 6 a.m.) were performed in 8 patients. Administration of propranolol (50 mg three times daily) over a period of 4 weeks was followed by a significant reduction in BP, PRA and PA. PC remained unaltered. The pattern of rhythmic secretion of renin was abolished whereas that of aldosterone persisted at a lower level. Prindolol (10 mg three times daily) had a similar effect on BP as propranolol but failed to lower PRA and PA. Rhythmic secretion of renin was also markedly altered with prindolol in the absence of any change in rhythmicity of PA and PC. The hypotensive action of prindolol was not mediated via inhibition of renin release. The dissociation between PRA and PA rhythmicity indicates that during beta-adrenergic blockade diurnal rhythm of aldosterone secretion is not regulated by the renin-angiotensin-system. Rhythmicity of PC was normal, indicating that also ACTH-secretion was unaltered. Thus, under beta-blockade unchanged diurnal rhythm of aldosterone may be due to normal ACTH-secretion."}
{"id": "PMID:241887", "title": "Effect of beta-adrenoceptor blocking drugs, physostigmine, and atropine on the toxicity of doxepin in mice.", "content": "Large doses of doxepin given intravenously to animals cause tachyarrhythmias, and still higher doses lead to a progressive and, finally, lethal bradycardia. The effect of pretreatment with five different beta-adrenoceptor blocking drugs (propranolol, alprenolol, practolol, metoprolol or tolamolol), p physostigmine, or atropine on these toxic actions of doxepin was investigated. Mice were sedated with diazepam. Doxepin was injected i.v. 0.1 mg every 15 sec until death. ECG was recorded at 10 sec after every injection. All five beta-blockers injected  i.p. 30 min before doxepin inhibited the doxepin-induced tachyarrhythmias. None of the drugs prevented or postponed the death of mice. Large doses of beta-blockers dose-dependently enhanced the doxepin-induced bradycardia and accelerated death. The cardioselective beta-blocking drugs practolol and metoprolol proved less active in enhancing bradycardia than the third cardio-selective drug, tolamolol, and non-selective propranolol and alprenolol. This difference may have resulted from properties other than beta-blockade since practolol and metoprolol lack the \"cardiodepressant\" and local anaesthetic properties. Since physostigmine and atropine did not modify the doxepin effects the anticholinergic property may not be important in the severe cardiotoxic effects of doxepin.", "contents": "Effect of beta-adrenoceptor blocking drugs, physostigmine, and atropine on the toxicity of doxepin in mice. Large doses of doxepin given intravenously to animals cause tachyarrhythmias, and still higher doses lead to a progressive and, finally, lethal bradycardia. The effect of pretreatment with five different beta-adrenoceptor blocking drugs (propranolol, alprenolol, practolol, metoprolol or tolamolol), p physostigmine, or atropine on these toxic actions of doxepin was investigated. Mice were sedated with diazepam. Doxepin was injected i.v. 0.1 mg every 15 sec until death. ECG was recorded at 10 sec after every injection. All five beta-blockers injected  i.p. 30 min before doxepin inhibited the doxepin-induced tachyarrhythmias. None of the drugs prevented or postponed the death of mice. Large doses of beta-blockers dose-dependently enhanced the doxepin-induced bradycardia and accelerated death. The cardioselective beta-blocking drugs practolol and metoprolol proved less active in enhancing bradycardia than the third cardio-selective drug, tolamolol, and non-selective propranolol and alprenolol. This difference may have resulted from properties other than beta-blockade since practolol and metoprolol lack the \"cardiodepressant\" and local anaesthetic properties. Since physostigmine and atropine did not modify the doxepin effects the anticholinergic property may not be important in the severe cardiotoxic effects of doxepin."}
{"id": "PMID:241892", "title": "Effect of sodium cellulose phosphate therapy on crystallization of calcium oxalate in urine.", "content": "Effects of oral sodium cellulose phosphate therapy (5 g three times a day with meals for 4 days) on renal excretion of oxalate and on the crystallization of calcium oxalate in urine were examined in six patients with absorptive hypercalciuria on a constant metabolic dietary regimen. During treatment, urinary oxalate increased by 9-50 mg/day. However, urinary calcium decreased by 138-225 mg/day (50%-70%). Thus, the state of saturation of urine with respect to calcium oxalate decreased or did not change significantly. There was no consistent or significant change in the formation product ratio (limit of metastability) or in the crystal growth of calcium oxalate in urine.", "contents": "Effect of sodium cellulose phosphate therapy on crystallization of calcium oxalate in urine. Effects of oral sodium cellulose phosphate therapy (5 g three times a day with meals for 4 days) on renal excretion of oxalate and on the crystallization of calcium oxalate in urine were examined in six patients with absorptive hypercalciuria on a constant metabolic dietary regimen. During treatment, urinary oxalate increased by 9-50 mg/day. However, urinary calcium decreased by 138-225 mg/day (50%-70%). Thus, the state of saturation of urine with respect to calcium oxalate decreased or did not change significantly. There was no consistent or significant change in the formation product ratio (limit of metastability) or in the crystal growth of calcium oxalate in urine."}
{"id": "PMID:241893", "title": "Regulation of glycolysis in Neurospora crassa. Kinetic properties of pyruvate kinase.", "content": "Pyruvate kinase (ATP:pyruvate phosphotransferase, EC 2.7.1.40), extracted from the mycelium of Neurospora crassa has been purified 560-fold by precipitation with ammonium sulphate, chromatography with DEAE-Sephadex, and gel filtration with Sephadex G-200. Potassium and magnesium are required for enzyme activity. Fructose, 1,6-diphosphate is the only physiological activator found for the enzyme. In decreasing order of potency, citrate, oxalacetate, calcium, and ATP are inhibitors. Phosphoenolpyruvate is cooperatively bound by the enzyme and the cooperatively is reduced by ATP and completely eliminated by fructose-1,6-diphosphate. Lowering of pH from 7-5 to 5-5 changes the Hill coefficient from 2-7 to 1-0. Substitution of ADP by other nucleotides reduces enzyme activity. Manganese can substitute for the cofactor magnesium, but the reaction velocity is then reduced. MgADP- is cooperatively bound by the enzyme and inhibition of the enzyme occurs only when either magnesium or ADP is in excess of the other beyond the optimum concentration. These kinetics properties of pyruvate kinase are compatible with the role of a regulator of glycolysis in Neurospora crassa.", "contents": "Regulation of glycolysis in Neurospora crassa. Kinetic properties of pyruvate kinase. Pyruvate kinase (ATP:pyruvate phosphotransferase, EC 2.7.1.40), extracted from the mycelium of Neurospora crassa has been purified 560-fold by precipitation with ammonium sulphate, chromatography with DEAE-Sephadex, and gel filtration with Sephadex G-200. Potassium and magnesium are required for enzyme activity. Fructose, 1,6-diphosphate is the only physiological activator found for the enzyme. In decreasing order of potency, citrate, oxalacetate, calcium, and ATP are inhibitors. Phosphoenolpyruvate is cooperatively bound by the enzyme and the cooperatively is reduced by ATP and completely eliminated by fructose-1,6-diphosphate. Lowering of pH from 7-5 to 5-5 changes the Hill coefficient from 2-7 to 1-0. Substitution of ADP by other nucleotides reduces enzyme activity. Manganese can substitute for the cofactor magnesium, but the reaction velocity is then reduced. MgADP- is cooperatively bound by the enzyme and inhibition of the enzyme occurs only when either magnesium or ADP is in excess of the other beyond the optimum concentration. These kinetics properties of pyruvate kinase are compatible with the role of a regulator of glycolysis in Neurospora crassa."}
{"id": "PMID:241894", "title": "Survival of Poria weirii on paired plots in alder and conifer stands.", "content": "Cubes of Douglas-fir wood decayed by Poria weirii (Murr.) Murr. were buried for 12 months on paired plots in red alder and in confier soils on the Cascade Head Experimental Forest. Survival of the fungus was not significantly different in the two soils, although pH was significantly lower and nitrate content significantly higher in alder soils. Even though effects on fungus survival were nil, red alder, for other reasons, might still be used to reduce damage caused by P. weirii root not on areas of heavy infestation.", "contents": "Survival of Poria weirii on paired plots in alder and conifer stands. Cubes of Douglas-fir wood decayed by Poria weirii (Murr.) Murr. were buried for 12 months on paired plots in red alder and in confier soils on the Cascade Head Experimental Forest. Survival of the fungus was not significantly different in the two soils, although pH was significantly lower and nitrate content significantly higher in alder soils. Even though effects on fungus survival were nil, red alder, for other reasons, might still be used to reduce damage caused by P. weirii root not on areas of heavy infestation."}
{"id": "PMID:241896", "title": "The emergency treatment of poisoning in children.", "content": "The various methods commonly used to reduce the amount of a poison that will be absorbed from the alimentary tract are evaluated according to safety, speed of action, effectiveness and patient acceptability. The conclusion is reached on the evidence available that syrup of ipecacuanha is the method of choice in the routine emergency treatment of childhood poisonings. The indications for other methods are defined.", "contents": "The emergency treatment of poisoning in children. The various methods commonly used to reduce the amount of a poison that will be absorbed from the alimentary tract are evaluated according to safety, speed of action, effectiveness and patient acceptability. The conclusion is reached on the evidence available that syrup of ipecacuanha is the method of choice in the routine emergency treatment of childhood poisonings. The indications for other methods are defined."}
{"id": "PMID:241899", "title": "[Ventricular aneurysm and coronary heart disease. Pathophysiology, differential therapy, and postoperative haemodynamics (author's transl)].", "content": "In the course of coronary heart disease an aneurysmal dilatation of the left ventricle may occur. This may be an additional risk for the patient by changed haemodynamics. Depending on the extent of the aneurysm and the contractile potency of the remaining myocard the cardiac compensation may be sufficient. A reduction of the pump efficiency is not necessarily the consequence. In case there is an increasing cardiac insufficiency by means of a pathologic ventricular filling pressure pulse, the best therapy is digitalis in combination with a reduction of volume by sodium-selective diuretics. Under same haemodynamic conditions the treatment of angina pectoris consists of long acting nitrites in combination with a betablocking agent having some intrinsic activity. Special care for the choic of medicaments has to be taken in relation to the sufficiency of the remaining myocard, if an antiarrhythmic therapy is necessary. If there is no stabilisation of the haemodynamic parameters by conservative therapy, the left ventricular function is meliorated by surgical aneurysmectomy. The data demonstrate, that under resting condition a normalisation and under exercise condition at least a melioration of pulse pressure and circulation is achieved after resection of the aneurysma. A small but measurable decrease in cardiac output under exercise condition is the consequence of a persisting cardiodepressive effect due to the operation.", "contents": "[Ventricular aneurysm and coronary heart disease. Pathophysiology, differential therapy, and postoperative haemodynamics (author's transl)]. In the course of coronary heart disease an aneurysmal dilatation of the left ventricle may occur. This may be an additional risk for the patient by changed haemodynamics. Depending on the extent of the aneurysm and the contractile potency of the remaining myocard the cardiac compensation may be sufficient. A reduction of the pump efficiency is not necessarily the consequence. In case there is an increasing cardiac insufficiency by means of a pathologic ventricular filling pressure pulse, the best therapy is digitalis in combination with a reduction of volume by sodium-selective diuretics. Under same haemodynamic conditions the treatment of angina pectoris consists of long acting nitrites in combination with a betablocking agent having some intrinsic activity. Special care for the choic of medicaments has to be taken in relation to the sufficiency of the remaining myocard, if an antiarrhythmic therapy is necessary. If there is no stabilisation of the haemodynamic parameters by conservative therapy, the left ventricular function is meliorated by surgical aneurysmectomy. The data demonstrate, that under resting condition a normalisation and under exercise condition at least a melioration of pulse pressure and circulation is achieved after resection of the aneurysma. A small but measurable decrease in cardiac output under exercise condition is the consequence of a persisting cardiodepressive effect due to the operation."}
{"id": "PMID:241901", "title": "[Oral application of an acidiferous drug and its effect on fasting-blood-sugar (author's transl)].", "content": "Oral application of an acidiferous drug has no effect on fasting-blood-sugar. This is also true in patients, who suffered from anacidity or subacidity, even if stomachical-pH could be lowered to 2,0 or less.", "contents": "[Oral application of an acidiferous drug and its effect on fasting-blood-sugar (author's transl)]. Oral application of an acidiferous drug has no effect on fasting-blood-sugar. This is also true in patients, who suffered from anacidity or subacidity, even if stomachical-pH could be lowered to 2,0 or less."}
{"id": "PMID:241928", "title": "The isolation and characterization of glutamine-requiring strains of Escherichia coli K12.", "content": "Mutants of Escherichia coli K12 requiring glutamine as a nitrogen source were isolated, and characterized as lacking glutamine synthetase activity. Temperature sensitive revertants of one of the mutants had a heat labile glutamine synthetase, while temperature insensitive revertants had a glutamine synthetase which was thermostable in vitro, indicating that the mutation was in the structural gene for the enzyme. All of the mutations mapped in the same region of the chromosome suggesting that they might all be in the same gene. The glutamine synthetase gene (gln) was located on the E. coli chromosome by conjugation and P1-mediated transduction at minute 77. The gln gene cotransduced with the genes for oleate degradation (old), and the genes for L-rhamnose utilization (rha). The most probable gene order is old-gln-rha.", "contents": "The isolation and characterization of glutamine-requiring strains of Escherichia coli K12. Mutants of Escherichia coli K12 requiring glutamine as a nitrogen source were isolated, and characterized as lacking glutamine synthetase activity. Temperature sensitive revertants of one of the mutants had a heat labile glutamine synthetase, while temperature insensitive revertants had a glutamine synthetase which was thermostable in vitro, indicating that the mutation was in the structural gene for the enzyme. All of the mutations mapped in the same region of the chromosome suggesting that they might all be in the same gene. The glutamine synthetase gene (gln) was located on the E. coli chromosome by conjugation and P1-mediated transduction at minute 77. The gln gene cotransduced with the genes for oleate degradation (old), and the genes for L-rhamnose utilization (rha). The most probable gene order is old-gln-rha."}
{"id": "PMID:241929", "title": "Glycolytic metabolism in cultured cells of the nervous system. I. Glucose transport and metabolism in the C-6 glioma cell line.", "content": "The transport and metabolism of glucose was examined in monolayers of C-6 glioma cells. 1) Glucose transport appeared to have both a low (Km = 7.74 mM) and a high (Km = 1.16 mM) affinity site in C-6cells; whereas 2-deoxyglucose had only one (Km = 3.7 mM). 2) A large portion of the accumulated glucose was rapidly metabolized to the two glycolytic end products, lactate and pyruvate, and then extruded into the medium. The temperature-dependent efflux of lactate and pyruvate was linear up to 2 hrs with 6 to 10 times more lactate being extruded into the medium than pyruvate. 3) The efflux of lactate and pyruvate increased with increasing extracellular (medium) pH. The presence of 5 percent CO2 not only inhibited the acid efflux but also inhibited the short-term uptake of glucose. The CO2 effect was attributed to a lowering of the medium pH since bicarbonate alone either increased or did not inhibit efflux. 4) Valinomycin increased the levels of cellular lactate but not those of pyruvate by almost three-fold. Lactate efflux was stimulated while that of pyruvate was inhibited. The addition of 5 percent CO2 increased the cellular levels of both lactate and pyruvate, but unlike valinomycin decreased the acid efflux. Idoacetate inhibited the acid efflux by 50 percent suggesting that glycolysis is necessary for efflux.", "contents": "Glycolytic metabolism in cultured cells of the nervous system. I. Glucose transport and metabolism in the C-6 glioma cell line. The transport and metabolism of glucose was examined in monolayers of C-6 glioma cells. 1) Glucose transport appeared to have both a low (Km = 7.74 mM) and a high (Km = 1.16 mM) affinity site in C-6cells; whereas 2-deoxyglucose had only one (Km = 3.7 mM). 2) A large portion of the accumulated glucose was rapidly metabolized to the two glycolytic end products, lactate and pyruvate, and then extruded into the medium. The temperature-dependent efflux of lactate and pyruvate was linear up to 2 hrs with 6 to 10 times more lactate being extruded into the medium than pyruvate. 3) The efflux of lactate and pyruvate increased with increasing extracellular (medium) pH. The presence of 5 percent CO2 not only inhibited the acid efflux but also inhibited the short-term uptake of glucose. The CO2 effect was attributed to a lowering of the medium pH since bicarbonate alone either increased or did not inhibit efflux. 4) Valinomycin increased the levels of cellular lactate but not those of pyruvate by almost three-fold. Lactate efflux was stimulated while that of pyruvate was inhibited. The addition of 5 percent CO2 increased the cellular levels of both lactate and pyruvate, but unlike valinomycin decreased the acid efflux. Idoacetate inhibited the acid efflux by 50 percent suggesting that glycolysis is necessary for efflux."}
{"id": "PMID:241930", "title": "The kinetics of pancreatic ribonuclease reaction with alkaline and acidic forms of poly A.", "content": "The RNase hydrolysis of random-coil (alkaline form) poly A follows biphasic kinetics at low salt concentrations. However, its resistance to RNase increases with the ionic strength. Helical (acidic form) poly A is alos susceptible to RNase but its hydrolysis follows first-order kinetics, and its resistance increases as the pH is lowered. These conformation-dependent kinetics of poly A hydrolysis are similar to those obtained in the hydrolysis of cellular RNA and reovirus double-stranded RNA.", "contents": "The kinetics of pancreatic ribonuclease reaction with alkaline and acidic forms of poly A. The RNase hydrolysis of random-coil (alkaline form) poly A follows biphasic kinetics at low salt concentrations. However, its resistance to RNase increases with the ionic strength. Helical (acidic form) poly A is alos susceptible to RNase but its hydrolysis follows first-order kinetics, and its resistance increases as the pH is lowered. These conformation-dependent kinetics of poly A hydrolysis are similar to those obtained in the hydrolysis of cellular RNA and reovirus double-stranded RNA."}
{"id": "PMID:241932", "title": "[Treatment of ischemic heart disease with beta-receptor blockers and isosorbide dinitrate (author's transl)].", "content": "The effects of a beta-receptor blocker (Betadrenol), an isosorbide dinitrate preparation (Isoket) and the combination of the two substances (Betaket) were compared with a placebo in a controlled double blind trial in 20 patients with confirmed attacks of angina pectoris and/or ischemic changes in the ECG on ergometer exercise. Important assessment criteria of the efficacy were regression of ischemic ECG changes on standardized ergometer exercise, increase in load resistance and the nitroglycerine requirement. Treatment with the combination of betablocker and isosorbide dinitrate (Betaket) was more effective in comparison to treatment with the individual substances.", "contents": "[Treatment of ischemic heart disease with beta-receptor blockers and isosorbide dinitrate (author's transl)]. The effects of a beta-receptor blocker (Betadrenol), an isosorbide dinitrate preparation (Isoket) and the combination of the two substances (Betaket) were compared with a placebo in a controlled double blind trial in 20 patients with confirmed attacks of angina pectoris and/or ischemic changes in the ECG on ergometer exercise. Important assessment criteria of the efficacy were regression of ischemic ECG changes on standardized ergometer exercise, increase in load resistance and the nitroglycerine requirement. Treatment with the combination of betablocker and isosorbide dinitrate (Betaket) was more effective in comparison to treatment with the individual substances."}
{"id": "PMID:241933", "title": "[Insulin allergy and insulin resistance (author's transl)].", "content": "The antigenicity of insulin is the cause of the side effects of insulin therapy such as insulin allergy, lipoatrophy at the site of injection and insulin resistance. Factors inherent in the individual patient are decisive for the antigenicity of insulin, as well as species specificity of the insulin,purity and galenical form. Clinical aspects and possibilities for treatment of insulin allergy, lipoatrophy and insulin resistance are discussed in relation to our own cases.", "contents": "[Insulin allergy and insulin resistance (author's transl)]. The antigenicity of insulin is the cause of the side effects of insulin therapy such as insulin allergy, lipoatrophy at the site of injection and insulin resistance. Factors inherent in the individual patient are decisive for the antigenicity of insulin, as well as species specificity of the insulin,purity and galenical form. Clinical aspects and possibilities for treatment of insulin allergy, lipoatrophy and insulin resistance are discussed in relation to our own cases."}
{"id": "PMID:241934", "title": "[The diagnostic significance of immunoglobulin determination in chronic liver diseases. I. Differential diagnostic accuracy of immunoglobulin changes and enzyme activities (author's transl)].", "content": "715 patients with hepatobiliary diseases came for examination, who because of the morphological findings are classified in diagnostic groups. The immunoglobulin measurements of IGG, IGA, IGM were determined and assessed in combination with enzymatic investigations of GOT, GPT, AP and GGTP. Typical group-specific changes were only found in primary biliary liver diseases and toxic cirrhoses of the liver, all acute or chronic inflammatory liver diseases could not be separated and by inference from the final diagnosis showed great errors in classification. Data on the raised mean levels of immunoglobulins in the individual diagnostic groups were demonstrable, but the range limits were so widely scattered that their differential diagnostic valence is of no consequence. Immunoglobulins may appear to be of interest for the observation of the course of liver diseases, but they are unsuitable for diagnostic purposes.", "contents": "[The diagnostic significance of immunoglobulin determination in chronic liver diseases. I. Differential diagnostic accuracy of immunoglobulin changes and enzyme activities (author's transl)]. 715 patients with hepatobiliary diseases came for examination, who because of the morphological findings are classified in diagnostic groups. The immunoglobulin measurements of IGG, IGA, IGM were determined and assessed in combination with enzymatic investigations of GOT, GPT, AP and GGTP. Typical group-specific changes were only found in primary biliary liver diseases and toxic cirrhoses of the liver, all acute or chronic inflammatory liver diseases could not be separated and by inference from the final diagnosis showed great errors in classification. Data on the raised mean levels of immunoglobulins in the individual diagnostic groups were demonstrable, but the range limits were so widely scattered that their differential diagnostic valence is of no consequence. Immunoglobulins may appear to be of interest for the observation of the course of liver diseases, but they are unsuitable for diagnostic purposes."}
{"id": "PMID:241943", "title": "Effect of tolbutamide on aminophylline-, 3,5-AMP-dibutyrate- or glucagon-induced insulin release from pancreatic islets after impairment of pyridine nucleotide metabolism caused by 6-aminonicotinamide (6-AN).", "content": "The effect of tolbutamide on pyridine nucleotides and insulin secretion stimulated by aminophylline, 3,5-AMP-dibutyrate or glucagon was studied in pancreatic islets of rats previously treated with 6-aminonicotinamide (6-AN), an inhibitor of pyridine nucleotide synthesis. After being incubated for 60 min in a Krebs-Ringer-Bicarbonate-Buffer in the absence of glucose, pancreatic islets of rats i.p. injected with 35 mg/kg of 6-AN 6 hrs before pancreas removal contained about 30% less NADP and NADPH than did islets of control rats. No changes of NDA or NADH were observed in islets of 6-AN-treated animals. Addition of 16.5 mM glucose led to an increase of NADH, NADPH and a decrease of NADP in islets of both groups of animals; NAD levels remained unchanged. In vitro addition of tolbutamide to islets of control rats did not affect the levels of NADPH or NADP in the presence of 5.5 mM glucose. When 16.5 mM glucose were present, a decrease of NADPH and an increase of NADP was obvious. No effect of tolbutamide on insular NADPH or NADP was observed in islets of rats previously treated with 6-AN be it in the presence of 5.5  or 16.5 mM glucose. In islets of 6-AN-treated rats insulin release in response to aminophylline or 3,5-AMP-dibutyrate in the presence of 5.5 mM glucose was significantly depressed, when compared to islets of untreated controls. Addition of tolbutamide increased insulin release due to aminophylline, 3,5-AMP-dibutyrate or glucagon islets of controls. Tolbutamide alone was without effect. In islets of 6-AN-treated rats aminophylline, 3,5-AMP-dibutyrate or glucagon stimulated insulin release only when tolbutamide was present. Our data suggest that there is no direct interference of tolbutamide with pyridine nucleotides of pancreatic islets, and that tolbutamide increases the secretory response of the beta-cell to aminophylline, 3,5-AMP-dibutyrate or glucagon when insulin release due to these agents is inhibited during decrease of insular NADP and NADPH, caused by 6-AN.", "contents": "Effect of tolbutamide on aminophylline-, 3,5-AMP-dibutyrate- or glucagon-induced insulin release from pancreatic islets after impairment of pyridine nucleotide metabolism caused by 6-aminonicotinamide (6-AN). The effect of tolbutamide on pyridine nucleotides and insulin secretion stimulated by aminophylline, 3,5-AMP-dibutyrate or glucagon was studied in pancreatic islets of rats previously treated with 6-aminonicotinamide (6-AN), an inhibitor of pyridine nucleotide synthesis. After being incubated for 60 min in a Krebs-Ringer-Bicarbonate-Buffer in the absence of glucose, pancreatic islets of rats i.p. injected with 35 mg/kg of 6-AN 6 hrs before pancreas removal contained about 30% less NADP and NADPH than did islets of control rats. No changes of NDA or NADH were observed in islets of 6-AN-treated animals. Addition of 16.5 mM glucose led to an increase of NADH, NADPH and a decrease of NADP in islets of both groups of animals; NAD levels remained unchanged. In vitro addition of tolbutamide to islets of control rats did not affect the levels of NADPH or NADP in the presence of 5.5 mM glucose. When 16.5 mM glucose were present, a decrease of NADPH and an increase of NADP was obvious. No effect of tolbutamide on insular NADPH or NADP was observed in islets of rats previously treated with 6-AN be it in the presence of 5.5  or 16.5 mM glucose. In islets of 6-AN-treated rats insulin release in response to aminophylline or 3,5-AMP-dibutyrate in the presence of 5.5 mM glucose was significantly depressed, when compared to islets of untreated controls. Addition of tolbutamide increased insulin release due to aminophylline, 3,5-AMP-dibutyrate or glucagon islets of controls. Tolbutamide alone was without effect. In islets of 6-AN-treated rats aminophylline, 3,5-AMP-dibutyrate or glucagon stimulated insulin release only when tolbutamide was present. Our data suggest that there is no direct interference of tolbutamide with pyridine nucleotides of pancreatic islets, and that tolbutamide increases the secretory response of the beta-cell to aminophylline, 3,5-AMP-dibutyrate or glucagon when insulin release due to these agents is inhibited during decrease of insular NADP and NADPH, caused by 6-AN."}
{"id": "PMID:241944", "title": "Effects of arecoline and cholinesterase inhibitors on cyclic guanosine 3',5'-monophosphate and adenosine 3'.5'-monophosphate in mouse brain.", "content": "In mice, Arecoline in vivo dose-dependently increased the cGMP concentrations of the cerebellum and the \"cereberum\" (= parts of cortex, hippocampus, hypothalamus, thalamus, striatum and midbrain) without influencing thecAMP levels. The cholinesterase inhibitors paraoxon and physostigmine caused an elevation only in \"cerebrum\", whereas the cGMP content of the cerebellum even decreased. Pretreatment with atropine prevented the rise in cGMP levels as well as the symptoms of cholinergic stimulation elicited by arecoline or paraoxon. Diazepam reduced cGMP levels below control values and blocked the effect of arecoline, while typical symptoms due to arecoline, e.g., tremor and salivation remained unaffected. The tripeptide prolyl-leucyl-glycinamide (MIF) had no effect on either cGMP values or the peripheral signs of cholinergic stimulation elicited by arecoline. The results show that elevation of cGMP in the central nervous system caused by cholinomimetic agents can be prevented not only by cholinolytics, blocking muscarinic receptors but also by influencing other mechanisms to be discussed.", "contents": "Effects of arecoline and cholinesterase inhibitors on cyclic guanosine 3',5'-monophosphate and adenosine 3'.5'-monophosphate in mouse brain. In mice, Arecoline in vivo dose-dependently increased the cGMP concentrations of the cerebellum and the \"cereberum\" (= parts of cortex, hippocampus, hypothalamus, thalamus, striatum and midbrain) without influencing thecAMP levels. The cholinesterase inhibitors paraoxon and physostigmine caused an elevation only in \"cerebrum\", whereas the cGMP content of the cerebellum even decreased. Pretreatment with atropine prevented the rise in cGMP levels as well as the symptoms of cholinergic stimulation elicited by arecoline or paraoxon. Diazepam reduced cGMP levels below control values and blocked the effect of arecoline, while typical symptoms due to arecoline, e.g., tremor and salivation remained unaffected. The tripeptide prolyl-leucyl-glycinamide (MIF) had no effect on either cGMP values or the peripheral signs of cholinergic stimulation elicited by arecoline. The results show that elevation of cGMP in the central nervous system caused by cholinomimetic agents can be prevented not only by cholinolytics, blocking muscarinic receptors but also by influencing other mechanisms to be discussed."}
{"id": "PMID:241946", "title": "The autoregulatory capability of Galen's rete cerebri and its connections.", "content": "The rete, a vascular system between the extra- and intracerebral arteries of certain animals, may have a variety of functions in different species. The calibres of the vessels of the rete and its arteries of supply have been measured under different conditions of blood pressure and PaCO2. It has been shown that the rete and its afferent arteries behave in an autoregulatory fashion down to a blood pressure of 60 mmHg. They also dilate with a rise in PaCO2. It has also been found that some parts of the system dilate even when the blood pressure drops lower than 60 mmHg. It is suggested that this autoregulatory capacity of extradural vessels limits the requirement for CSF spaces to change with blood pressure changes. A general rule has been sought which would link the known facts about cerebral autoregulation and the possession of extra- to intracranial anastomoses with the bodily shape and posture of the particular animal.", "contents": "The autoregulatory capability of Galen's rete cerebri and its connections. The rete, a vascular system between the extra- and intracerebral arteries of certain animals, may have a variety of functions in different species. The calibres of the vessels of the rete and its arteries of supply have been measured under different conditions of blood pressure and PaCO2. It has been shown that the rete and its afferent arteries behave in an autoregulatory fashion down to a blood pressure of 60 mmHg. They also dilate with a rise in PaCO2. It has also been found that some parts of the system dilate even when the blood pressure drops lower than 60 mmHg. It is suggested that this autoregulatory capacity of extradural vessels limits the requirement for CSF spaces to change with blood pressure changes. A general rule has been sought which would link the known facts about cerebral autoregulation and the possession of extra- to intracranial anastomoses with the bodily shape and posture of the particular animal."}
{"id": "PMID:241947", "title": "Infantile Gaucher's disease: glucocerebrosidase deficiency in peripheral blood leukocytes and cultured fibroblasts.", "content": "A patient with infantile Gancher's disease is described. A marked decrease of the activity of beta-glucosidase at the lower pH 4.2 was found in peripheral blood leukocytes, whereas in cultured skin fibroblasts the activity at both pH'S 4.2 and 5.2 was decreased. Examining the leukocytes of the heterozygous parents the activities of beta-glucosidase at both pH's were within the values of controls, but the ratio's of activity of pH 5.2 to that at pH 4.2 were increased lying between the ratio's from the patient and controls.", "contents": "Infantile Gaucher's disease: glucocerebrosidase deficiency in peripheral blood leukocytes and cultured fibroblasts. A patient with infantile Gancher's disease is described. A marked decrease of the activity of beta-glucosidase at the lower pH 4.2 was found in peripheral blood leukocytes, whereas in cultured skin fibroblasts the activity at both pH'S 4.2 and 5.2 was decreased. Examining the leukocytes of the heterozygous parents the activities of beta-glucosidase at both pH's were within the values of controls, but the ratio's of activity of pH 5.2 to that at pH 4.2 were increased lying between the ratio's from the patient and controls."}
{"id": "PMID:241948", "title": "[Metabolic alkalosis. Compensation mechanisms in the light of new experimental data].", "content": "Changes in arterial blood and erythrocyte acid-base and electrolyte balance in the course of acute alkalinisation caused by bicarbonate loading showed that extracellular alkalosis has no significant effect on the concentration of intraerythrocyte bicarbonate concentration, though a marked increase in pH and electrolyte balance within the red cell is apparent. Erythrocyte alkalinisation may thus be seen as essentially due to the escape of H+ ions, while the entry of Na+ ions is the main device by which the law of electroneutrality is respected. The literature suggests that lactic acid offers a source of H+ ions for destruction of bicarbonate, whereas the diffusion of the ion lactate within the cell is compensated by the release of Cl-. In addition, the data now reported indicate that the red cell is a sufficiently valid model for the study of phenomena occurring within the intracellular compartment when a state of extracellular alkalinisation in created.", "contents": "[Metabolic alkalosis. Compensation mechanisms in the light of new experimental data]. Changes in arterial blood and erythrocyte acid-base and electrolyte balance in the course of acute alkalinisation caused by bicarbonate loading showed that extracellular alkalosis has no significant effect on the concentration of intraerythrocyte bicarbonate concentration, though a marked increase in pH and electrolyte balance within the red cell is apparent. Erythrocyte alkalinisation may thus be seen as essentially due to the escape of H+ ions, while the entry of Na+ ions is the main device by which the law of electroneutrality is respected. The literature suggests that lactic acid offers a source of H+ ions for destruction of bicarbonate, whereas the diffusion of the ion lactate within the cell is compensated by the release of Cl-. In addition, the data now reported indicate that the red cell is a sufficiently valid model for the study of phenomena occurring within the intracellular compartment when a state of extracellular alkalinisation in created."}
{"id": "PMID:241949", "title": "[Current evaluation of beta-adrenergic agents in the treatment of bronchial spasm].", "content": "The current status of beta-adrenergics in the treatment of bronchospasm is discussed. Personal experience is reviewed with special attention being paid to associations of the drugs on aminophylline, atropine and bechlomethasone dipropionate.", "contents": "[Current evaluation of beta-adrenergic agents in the treatment of bronchial spasm]. The current status of beta-adrenergics in the treatment of bronchospasm is discussed. Personal experience is reviewed with special attention being paid to associations of the drugs on aminophylline, atropine and bechlomethasone dipropionate."}
{"id": "PMID:241945", "title": "[Treatment of enuresis with Noveril].", "content": "The authors present their observations on treatment with Noveril of nocturnal enuresis in 49 children aged from 6 to 16 years. The drug is a derivative of dibenzodiazepine belonging to the group of thymoleptic agents with an action similar to that of imipramine. Noveril was given in doses from 20 to 100 mg daily during 3 to 9 weeks. In the final evaluation of the drug the frequency of enuresis before, during and after treatment was taken into account. In 25 cases an improvement was observed, usually in psychogenic nocturnal enuresis. Side effects included oral dryness, headaches and dizziness, and sleep disturbances observed in 4 cases. The tolerance of the drug was good. Noveril has a favourable effect in children with nocturnal enuresis, particularly of psychogenic origin.", "contents": "[Treatment of enuresis with Noveril]. The authors present their observations on treatment with Noveril of nocturnal enuresis in 49 children aged from 6 to 16 years. The drug is a derivative of dibenzodiazepine belonging to the group of thymoleptic agents with an action similar to that of imipramine. Noveril was given in doses from 20 to 100 mg daily during 3 to 9 weeks. In the final evaluation of the drug the frequency of enuresis before, during and after treatment was taken into account. In 25 cases an improvement was observed, usually in psychogenic nocturnal enuresis. Side effects included oral dryness, headaches and dizziness, and sleep disturbances observed in 4 cases. The tolerance of the drug was good. Noveril has a favourable effect in children with nocturnal enuresis, particularly of psychogenic origin."}
{"id": "PMID:241957", "title": "Strontium, lead and nickel incorporation into mouse calvaria in vitro.", "content": "Incorporation of strontium, lead and nickel radioisotopes was studied in mouse calvaria in tissue culture. About 90% of the incorporated strontium and 5-12% of the lead were recovered in the mineral phase of the calvaria (hot acid soluble fraction), whereas the nickel was recovered mainly in the organic phase (hot alkali soluble fraction). Metabolic inhibition enhanced the incorporation, which indicated that the mineral metabolism of the calvaria comprised ionic exchange or secondary mineralization phenomenons independent of the activity of bone cells but, possibly, guided by a metabolically active bone membrane.", "contents": "Strontium, lead and nickel incorporation into mouse calvaria in vitro. Incorporation of strontium, lead and nickel radioisotopes was studied in mouse calvaria in tissue culture. About 90% of the incorporated strontium and 5-12% of the lead were recovered in the mineral phase of the calvaria (hot acid soluble fraction), whereas the nickel was recovered mainly in the organic phase (hot alkali soluble fraction). Metabolic inhibition enhanced the incorporation, which indicated that the mineral metabolism of the calvaria comprised ionic exchange or secondary mineralization phenomenons independent of the activity of bone cells but, possibly, guided by a metabolically active bone membrane."}
{"id": "PMID:241961", "title": "Persistent and transient distal renal tubular acidosis with bicarbonate wasting.", "content": "Bicarbonate titration studies were performed on two patients with bicarbonate wasting distal renal tubular acidosis (RTA; patients 1 and 2) and on three patients (3,4, and 5) with classic distal RTA. Daily requirements of alkali were 4.5 mEq/kg body wt in patient 1, a 3-year-old boy, and 16 mEq/kg in patient 2, a 5-month-old male infant. In contrast, only 1.5-2 mEq/kg/24 hr alkali were required in the three patients with classic distal RTA (age 8 1/2- 22 years). Patient 1 had glucose-6-phosphate dehydrogenase deficiency and patient 3 had inner ear deafness as an associated anomaly. In patient 2, the acidification defect was transient. Mean fractional excretion of bicarbonate (ChCO3-/Cin) times 100 at a plasma concentration of HCO3 below 20 mmol/liter was 5.1% in patient 1, 11.6% in patient 2, and 1.7% in patients 3-5. Minimal urine pH during the study was 7.38 in patient 1, 7.66 in patient 2, and 6.78-6.97 in the other patients. Values of net acid excretion at plasma HCO3 = 16 mmol/liter were strongly negative in patients 1 and 2 (-75 and -195 mumol/100 ml glomerular filtrate (GF), respectively) but slightly positive in the three patients with classic RTA (+3 to +20 mumol/100 ml GF). The two patients with bicarbonate wasting distal RTA were thus clearly separated from the group of patients with classic distal RTA.", "contents": "Persistent and transient distal renal tubular acidosis with bicarbonate wasting. Bicarbonate titration studies were performed on two patients with bicarbonate wasting distal renal tubular acidosis (RTA; patients 1 and 2) and on three patients (3,4, and 5) with classic distal RTA. Daily requirements of alkali were 4.5 mEq/kg body wt in patient 1, a 3-year-old boy, and 16 mEq/kg in patient 2, a 5-month-old male infant. In contrast, only 1.5-2 mEq/kg/24 hr alkali were required in the three patients with classic distal RTA (age 8 1/2- 22 years). Patient 1 had glucose-6-phosphate dehydrogenase deficiency and patient 3 had inner ear deafness as an associated anomaly. In patient 2, the acidification defect was transient. Mean fractional excretion of bicarbonate (ChCO3-/Cin) times 100 at a plasma concentration of HCO3 below 20 mmol/liter was 5.1% in patient 1, 11.6% in patient 2, and 1.7% in patients 3-5. Minimal urine pH during the study was 7.38 in patient 1, 7.66 in patient 2, and 6.78-6.97 in the other patients. Values of net acid excretion at plasma HCO3 = 16 mmol/liter were strongly negative in patients 1 and 2 (-75 and -195 mumol/100 ml glomerular filtrate (GF), respectively) but slightly positive in the three patients with classic RTA (+3 to +20 mumol/100 ml GF). The two patients with bicarbonate wasting distal RTA were thus clearly separated from the group of patients with classic distal RTA."}
{"id": "PMID:241962", "title": "Bilirubin interaction with ganglioside: possible mechanism in kernicterus.", "content": "Reaction of bilirubin with increasing amounts of ganglioside purified from neonatal brain significantly alters the spectral absorption of bilirubin in proportion to the quantity of ganglioside added. Increments in absorbance occur at 353 nm with a prompt but transient increase at 486 nm. A decrease in absorbance occurs which is most marked at 447 nm. When gangliosides are added to bilirubin (9.1 mug/ml or 0.016 muM/ml), the decrease in absorbance is essentially linear up to the highest concentration of purified ganglioside tested (182 mug/ml or 0.097 muM/ml), which represents a molar ratio of 6.1:1. The asymptotic nature of the bilirubin-ganglioside reaction as measured by the decrease in absorbance with time suggests a stoichiometric relationship between the two substances. An isosbestic point was demonstrated at 405 nm. Observations reported here suggest bilirubin reaction with ganglioside is at least a two-step process.", "contents": "Bilirubin interaction with ganglioside: possible mechanism in kernicterus. Reaction of bilirubin with increasing amounts of ganglioside purified from neonatal brain significantly alters the spectral absorption of bilirubin in proportion to the quantity of ganglioside added. Increments in absorbance occur at 353 nm with a prompt but transient increase at 486 nm. A decrease in absorbance occurs which is most marked at 447 nm. When gangliosides are added to bilirubin (9.1 mug/ml or 0.016 muM/ml), the decrease in absorbance is essentially linear up to the highest concentration of purified ganglioside tested (182 mug/ml or 0.097 muM/ml), which represents a molar ratio of 6.1:1. The asymptotic nature of the bilirubin-ganglioside reaction as measured by the decrease in absorbance with time suggests a stoichiometric relationship between the two substances. An isosbestic point was demonstrated at 405 nm. Observations reported here suggest bilirubin reaction with ganglioside is at least a two-step process."}
{"id": "PMID:241968", "title": "Effect of beta-adrenoreceptor stimulants on exercise-induced asthma.", "content": "Exercise-induced asthma can be prevented or minimized by beta-adrenoreceptor stimulating drugs, which may elicit bronchodilation before exercise has begun or may enhance thebronchodilating effect of more prolonged exercise. Recently introduced beta-adrenoreceptor stimulants have longer durations of action than isoproterenol, are effective following oral administration, and are selective for beta-adrenoreceptors.", "contents": "Effect of beta-adrenoreceptor stimulants on exercise-induced asthma. Exercise-induced asthma can be prevented or minimized by beta-adrenoreceptor stimulating drugs, which may elicit bronchodilation before exercise has begun or may enhance thebronchodilating effect of more prolonged exercise. Recently introduced beta-adrenoreceptor stimulants have longer durations of action than isoproterenol, are effective following oral administration, and are selective for beta-adrenoreceptors."}
{"id": "PMID:241969", "title": "Exercise-induced asthma and competitive athletics.", "content": "Although swimming is their optimum sport and exercise, asthmatics should be encouraged to embrace a full and varied program of sport and physical education. Sports exclusion should be infrequent as possible. Pre-exercise cromolyn sodium with significantly reduce exercise-induced asthma (EIA) and salbutamol may be administered pre-exercise should EIA supervene. \"Warm-up\" is recommended. The current ruling which classes selective beta2-adrenocepter agonists as doping agents in sports should be rescinded.", "contents": "Exercise-induced asthma and competitive athletics. Although swimming is their optimum sport and exercise, asthmatics should be encouraged to embrace a full and varied program of sport and physical education. Sports exclusion should be infrequent as possible. Pre-exercise cromolyn sodium with significantly reduce exercise-induced asthma (EIA) and salbutamol may be administered pre-exercise should EIA supervene. \"Warm-up\" is recommended. The current ruling which classes selective beta2-adrenocepter agonists as doping agents in sports should be rescinded."}
{"id": "PMID:241970", "title": "Kinesthetic figural aftereffects in acute schizophrenia: a style of processing stimuli.", "content": "The Kinesthetic Figural Aftereffect test was administered to 106 psychiatric inpatients to assess styles of stimulus processing in schizophrenia. Three conditions were used: (1) standard stimulus conditions at the acute phase; (2) standard conditions, 7 wk. later, to evaluate stability over time; (3) reversed stimulus conditions to assess kinesthetic figural aftereffect generality under different stimulus conditions. Results indicated that: (1) schizophrenics reduced stimuli, but differences between patient groups were not significant. (2) Kinesthetic figural aftereffect stability over time was shown by nonschizophrenics (p less than .01) but not by schizophrenic and borderline patients. (3) All diagnostic groups reversed kinesthetic figural aftereffect responses under reversed stimulus conditions, e.g., former \"augmenters\" tended to reduce more under agumenting conditions, suggesting the importance of the specific stimulus conditions. (4) Acute schizophrenics showed a stimulus-governed style. (5) The results raise questions about kinesthetic figural aftereffects as a measure of response style.", "contents": "Kinesthetic figural aftereffects in acute schizophrenia: a style of processing stimuli. The Kinesthetic Figural Aftereffect test was administered to 106 psychiatric inpatients to assess styles of stimulus processing in schizophrenia. Three conditions were used: (1) standard stimulus conditions at the acute phase; (2) standard conditions, 7 wk. later, to evaluate stability over time; (3) reversed stimulus conditions to assess kinesthetic figural aftereffect generality under different stimulus conditions. Results indicated that: (1) schizophrenics reduced stimuli, but differences between patient groups were not significant. (2) Kinesthetic figural aftereffect stability over time was shown by nonschizophrenics (p less than .01) but not by schizophrenic and borderline patients. (3) All diagnostic groups reversed kinesthetic figural aftereffect responses under reversed stimulus conditions, e.g., former \"augmenters\" tended to reduce more under agumenting conditions, suggesting the importance of the specific stimulus conditions. (4) Acute schizophrenics showed a stimulus-governed style. (5) The results raise questions about kinesthetic figural aftereffects as a measure of response style."}
{"id": "PMID:241971", "title": "Use of mental imagery in psychotherapy: a critical review.", "content": "The paper presents arguments in favor of the use of mental imagery for therapeutic purposes. Several existing imagery approaches to psychotherapy are critically examined and suggestions for future inquiry are offered. The intimate relation between imagery and the affective-somatic processes is stressed.", "contents": "Use of mental imagery in psychotherapy: a critical review. The paper presents arguments in favor of the use of mental imagery for therapeutic purposes. Several existing imagery approaches to psychotherapy are critically examined and suggestions for future inquiry are offered. The intimate relation between imagery and the affective-somatic processes is stressed."}
{"id": "PMID:241973", "title": "The effects of calcium and magnesium on inhibitory junctional transmission in smooth muscle of guinea pig small intestine.", "content": "The membrane potential of smooth muscle cells in the circular layer of the guinea pig ileum was recorded using intracellular electrodes. Transmural stimulation, in the presence of atropine, caused a transient hyperpolarization, an inhibitory junction potential (IJP). IJP's are thought to result from the action of transmitter released from intramural inhibitory nerves. It has been reported that, in the guinea pig jejunum, the amplitude of the IJP resulting from field stimulation is not altered by changes in the calcium and magnesium ion concentration in the bathing solution. Experiments reported here have shown that the IJP amplitude decreased markedly on reducing the calcium ion concentration and or increasing the magnesium ion concentration. Indirect evidence is presented suggesting that the decrease in amplitude of the IJP is due to a decrease in the amount of transmitter released.", "contents": "The effects of calcium and magnesium on inhibitory junctional transmission in smooth muscle of guinea pig small intestine. The membrane potential of smooth muscle cells in the circular layer of the guinea pig ileum was recorded using intracellular electrodes. Transmural stimulation, in the presence of atropine, caused a transient hyperpolarization, an inhibitory junction potential (IJP). IJP's are thought to result from the action of transmitter released from intramural inhibitory nerves. It has been reported that, in the guinea pig jejunum, the amplitude of the IJP resulting from field stimulation is not altered by changes in the calcium and magnesium ion concentration in the bathing solution. Experiments reported here have shown that the IJP amplitude decreased markedly on reducing the calcium ion concentration and or increasing the magnesium ion concentration. Indirect evidence is presented suggesting that the decrease in amplitude of the IJP is due to a decrease in the amount of transmitter released."}
{"id": "PMID:241977", "title": "[Effect of potato starch on the level of volatile fatty acids and ammonia in sheep's rumen].", "content": "Two experiments were performed on adult sheep, which were given intraruminally potato starch in a single dose of 1500 g and in gradually increasing doses. The effect of starch on the level of volatile fatty acids, ammonia and the pH value was studied. In the rumen content, the level of pH slightly decreased and that of volatile fatty acids increased. Ammonia level decreased after starch administration. No lactic acid was found in the rumen content.", "contents": "[Effect of potato starch on the level of volatile fatty acids and ammonia in sheep's rumen]. Two experiments were performed on adult sheep, which were given intraruminally potato starch in a single dose of 1500 g and in gradually increasing doses. The effect of starch on the level of volatile fatty acids, ammonia and the pH value was studied. In the rumen content, the level of pH slightly decreased and that of volatile fatty acids increased. Ammonia level decreased after starch administration. No lactic acid was found in the rumen content."}
{"id": "PMID:241979", "title": "The influence of dopamine-beta-hydroxylase inhibitors on avoidance reaction in rat.", "content": "Dopamine-beta-hydroxylase inhibitors sodium diethyldithiocarbamate (DEDTC), disulfiram (DS), sodium dimethyldithiocarbamate (DMDTC), tetramethylthiuram disulfide (T) and alpha,alpha'-dipyridyl (DP) were studied for their influence on avoidance reaction in rat. These compounds were given in the doses inhibiting noradrenaline synthesis (decreasing the level of this amine in brain). They all inhibit avoidance reaction although certain differences were stated in the values of effective doses and in the power of action. DEDTC, DMDTC and DS appeared to be most effective. The results of experiments suggest that noradrenaline in brain has significant importance for the avoidance reaction in rats, similarly as it is assumed for dopamine.", "contents": "The influence of dopamine-beta-hydroxylase inhibitors on avoidance reaction in rat. Dopamine-beta-hydroxylase inhibitors sodium diethyldithiocarbamate (DEDTC), disulfiram (DS), sodium dimethyldithiocarbamate (DMDTC), tetramethylthiuram disulfide (T) and alpha,alpha'-dipyridyl (DP) were studied for their influence on avoidance reaction in rat. These compounds were given in the doses inhibiting noradrenaline synthesis (decreasing the level of this amine in brain). They all inhibit avoidance reaction although certain differences were stated in the values of effective doses and in the power of action. DEDTC, DMDTC and DS appeared to be most effective. The results of experiments suggest that noradrenaline in brain has significant importance for the avoidance reaction in rats, similarly as it is assumed for dopamine."}
{"id": "PMID:241980", "title": "Effect of nitrite on the phosphorolytic and hydrolytic glycogen decomposition in the heart and skeletal muscle.", "content": "Sodium nitrite produces indirectly an increase in glycogen phosphorolysis and hydrolysis both in the working heart muscle and in quiescent skeletal muscle. The results indicate this effect being related to catecholamines liberation as it never occurs after adrenalectomy, reserpine administration or beta-receptor blocking. The most significant effect of nitrite and adrenalin interaction consists in abolition of inhibiting influence of adrenalin upon glycogen hydrolysis which leads to significant increase in contribution of unphosphorylated sugars to the total pool of products liberated in a course of enhanced glycogenolysis process in the heart.", "contents": "Effect of nitrite on the phosphorolytic and hydrolytic glycogen decomposition in the heart and skeletal muscle. Sodium nitrite produces indirectly an increase in glycogen phosphorolysis and hydrolysis both in the working heart muscle and in quiescent skeletal muscle. The results indicate this effect being related to catecholamines liberation as it never occurs after adrenalectomy, reserpine administration or beta-receptor blocking. The most significant effect of nitrite and adrenalin interaction consists in abolition of inhibiting influence of adrenalin upon glycogen hydrolysis which leads to significant increase in contribution of unphosphorylated sugars to the total pool of products liberated in a course of enhanced glycogenolysis process in the heart."}
{"id": "PMID:241981", "title": "Potentiometric determination of theopaverin components in nonaqueous media.", "content": "Potentiometric method for determination of papaverine hydrochloride (PAP) and theobromine (Tb) in a mixture, without separation of the components was designed. Determinations were carried out in nonaqueous media, using solvents differentiating the strength of estimated bases.", "contents": "Potentiometric determination of theopaverin components in nonaqueous media. Potentiometric method for determination of papaverine hydrochloride (PAP) and theobromine (Tb) in a mixture, without separation of the components was designed. Determinations were carried out in nonaqueous media, using solvents differentiating the strength of estimated bases."}
{"id": "PMID:241982", "title": "IR analysis of crystalline samples of some urea derivatives.", "content": "The dependence of an IR spectrum of crystal samples of allantoin, barbital, chloroethylaminouracil (dopan), carbromal, 5-allyl-5-(beta-hydroxypropyl)-barbituric acid (ipronal) and theophyllin upon the method of crystals preparation was found after 3 months storage of crystals. There were no differences in the case of mephenytoin. The results obtained here demonstrate the possibility of an occurence of the majority of the analyzed substances as metastable polymorphic modifications in solid dosage forms. Furthermore, the IR identification of drugs requires crystallization of a substance from a particular solvent just before analysis.", "contents": "IR analysis of crystalline samples of some urea derivatives. The dependence of an IR spectrum of crystal samples of allantoin, barbital, chloroethylaminouracil (dopan), carbromal, 5-allyl-5-(beta-hydroxypropyl)-barbituric acid (ipronal) and theophyllin upon the method of crystals preparation was found after 3 months storage of crystals. There were no differences in the case of mephenytoin. The results obtained here demonstrate the possibility of an occurence of the majority of the analyzed substances as metastable polymorphic modifications in solid dosage forms. Furthermore, the IR identification of drugs requires crystallization of a substance from a particular solvent just before analysis."}
{"id": "PMID:241985", "title": "[Value of the determination of gamma glutamyl transpeptidase in the detection of hepatic metastases of bronch-pulmonary cancers].", "content": "The authors have dosed gamma glutamyl transpeptidase in 42 patients with primary bronchopulmonary cancer, of whom 14 had liver metastases. In these 14 patients the level of gamma glutamyl transpeptidase was always high, except in 1 case; while in the remaining lot, a moderate and mostly belated increase was noticed in only 32 percent of cases. The dosing of gamma glutamyl transpeptidase present some interest in the detection of liver metastases in primary bronchopulmonary cancers, specially when coupled with the dosing of alcaline phosphatase. Interpretation of results should take into account the existence of an associated liver-gall bladder involvement and of a recent surgical operation; both factors being capable of raising the level of gamma glutamyl transpeptidase.", "contents": "[Value of the determination of gamma glutamyl transpeptidase in the detection of hepatic metastases of bronch-pulmonary cancers]. The authors have dosed gamma glutamyl transpeptidase in 42 patients with primary bronchopulmonary cancer, of whom 14 had liver metastases. In these 14 patients the level of gamma glutamyl transpeptidase was always high, except in 1 case; while in the remaining lot, a moderate and mostly belated increase was noticed in only 32 percent of cases. The dosing of gamma glutamyl transpeptidase present some interest in the detection of liver metastases in primary bronchopulmonary cancers, specially when coupled with the dosing of alcaline phosphatase. Interpretation of results should take into account the existence of an associated liver-gall bladder involvement and of a recent surgical operation; both factors being capable of raising the level of gamma glutamyl transpeptidase."}
{"id": "PMID:241990", "title": "[Activity of certain dehydrogenases in accumulation and continuous-flow culture of paraffin-oxidizing yeast of the genus Candida].", "content": "Lability of NADP- and NAD-dependent glutamate dehydrogenases and malate dehydrogenases has been demonstrated during a change of the physiological activity of yeast Candida guilliermondii in the exponential phase of growth. Variations in the isoenzyme spectrum of the enzymes and total dehydrogenase activity of the yeast has been found during their transition from the accumulative to the continuous cultivation. Changes in the physiological state of yeast during their growth are accompanied by a rearrangement of the isoenzyme spectrum of malate dehydrogenase and glutamate dehydrogenases.", "contents": "[Activity of certain dehydrogenases in accumulation and continuous-flow culture of paraffin-oxidizing yeast of the genus Candida]. Lability of NADP- and NAD-dependent glutamate dehydrogenases and malate dehydrogenases has been demonstrated during a change of the physiological activity of yeast Candida guilliermondii in the exponential phase of growth. Variations in the isoenzyme spectrum of the enzymes and total dehydrogenase activity of the yeast has been found during their transition from the accumulative to the continuous cultivation. Changes in the physiological state of yeast during their growth are accompanied by a rearrangement of the isoenzyme spectrum of malate dehydrogenase and glutamate dehydrogenases."}
{"id": "PMID:241991", "title": "[Effect of temperature and the active acidity of the medium on the metabolism of reserve carbohydrates and the survivability of baker's yeast].", "content": "The effect of the cultivation temperature and active acidity of the medium on the contrent of trehalose and glycogen in baker's yeast was investigated. With the temperature growth from 20 to 40 degrees C the trehalose content in the cells increased, thus enhancing survivability of yeast during storage. The same results were observed upon temperature rise at the end of cultivation. pH of 4.5-5.0 intensified the synthesis of both reserve carbohydrates in baker's yeast.", "contents": "[Effect of temperature and the active acidity of the medium on the metabolism of reserve carbohydrates and the survivability of baker's yeast]. The effect of the cultivation temperature and active acidity of the medium on the contrent of trehalose and glycogen in baker's yeast was investigated. With the temperature growth from 20 to 40 degrees C the trehalose content in the cells increased, thus enhancing survivability of yeast during storage. The same results were observed upon temperature rise at the end of cultivation. pH of 4.5-5.0 intensified the synthesis of both reserve carbohydrates in baker's yeast."}
{"id": "PMID:241992", "title": "[Torula thermophila, strain UzPT-1 a thermophilic producer of proteolytic enzymes].", "content": "The properties of the thermophilous fungus Torula thermophila producing proteolytic enzymes are described. Oprimal conditions for its cultivation are established. The maximum action of the preparation isolated from the culture liquid filtrate is at pH 9-11. The temperature maximum of the enzyme activity is 70 degrees C.", "contents": "[Torula thermophila, strain UzPT-1 a thermophilic producer of proteolytic enzymes]. The properties of the thermophilous fungus Torula thermophila producing proteolytic enzymes are described. Oprimal conditions for its cultivation are established. The maximum action of the preparation isolated from the culture liquid filtrate is at pH 9-11. The temperature maximum of the enzyme activity is 70 degrees C."}
{"id": "PMID:241993", "title": "[Stableness of the alkaline protease of the fungus Torula thermophila strain UzPT-1 to heating and the action of Ca2+ ions].", "content": "Thermal stability of protease of the fungus Torula thermophila strain UzPT-1 was examined. The dependence of this property on the content of monomer and dimer forms in the preparation was also investigated. The preparations with a high content of the dimer form showed greater thermal stability in distilled water. The preparations/with the predominant monomer from retained thermal stability in buffer solutions at pH 8 and lost it in distilled water when stored in the cold (2-4 degrees C) for several days. The preparations which lost thermal stability upon ammonium sulphate precipitation recovered partially or completely after addition of Ca2+ ions at a concentration of 0.001 M.", "contents": "[Stableness of the alkaline protease of the fungus Torula thermophila strain UzPT-1 to heating and the action of Ca2+ ions]. Thermal stability of protease of the fungus Torula thermophila strain UzPT-1 was examined. The dependence of this property on the content of monomer and dimer forms in the preparation was also investigated. The preparations with a high content of the dimer form showed greater thermal stability in distilled water. The preparations/with the predominant monomer from retained thermal stability in buffer solutions at pH 8 and lost it in distilled water when stored in the cold (2-4 degrees C) for several days. The preparations which lost thermal stability upon ammonium sulphate precipitation recovered partially or completely after addition of Ca2+ ions at a concentration of 0.001 M."}
{"id": "PMID:241994", "title": "[Separation and characteristics of the proteolytic enzymes of Bacillus subtilis].", "content": "The composition of two protosubtilins -- proteolytic enzymes of the enzymes isolated from submerged cultures of two Bacillus subtilis strains was investigated. Each of the preparations contained two proteinases that differed in their pH optimum. Conditions of chromatographic separation of two proteinases on CM-52 cellulose were tested. With the use of specific inhibitors and specific substrates it has been shown that one of the proteinases belongs to metal enzymes and is inhibited by ethylene diamine tetracetate (EDTA). Another proteinase, which is probably serine proteinase, is inhibited by diazopropine fluorophosphate (DFP). The isoelectric point of neutral proteinase is 8.15-8.20.", "contents": "[Separation and characteristics of the proteolytic enzymes of Bacillus subtilis]. The composition of two protosubtilins -- proteolytic enzymes of the enzymes isolated from submerged cultures of two Bacillus subtilis strains was investigated. Each of the preparations contained two proteinases that differed in their pH optimum. Conditions of chromatographic separation of two proteinases on CM-52 cellulose were tested. With the use of specific inhibitors and specific substrates it has been shown that one of the proteinases belongs to metal enzymes and is inhibited by ethylene diamine tetracetate (EDTA). Another proteinase, which is probably serine proteinase, is inhibited by diazopropine fluorophosphate (DFP). The isoelectric point of neutral proteinase is 8.15-8.20."}
{"id": "PMID:241995", "title": "[Separation and characteristics of the acid proteinases from a surface culture of Aspergillus terricola].", "content": "The enzymic preparation isolated by ethanol precipitation from the aqueous extract of the surface culture of Aspergillus terricola was purified on biogel P-10, fractionated on SE-Sephadex. As a result, 10 fractions of acid proteinases that differed in pH optima and activity were obtained. After purification specific activity of some fractions per 1 mg protein increased 24-32-fold. The temperature optimum of the enzymes was at 50 degrees C and pH optimum at 2.5--2.8.", "contents": "[Separation and characteristics of the acid proteinases from a surface culture of Aspergillus terricola]. The enzymic preparation isolated by ethanol precipitation from the aqueous extract of the surface culture of Aspergillus terricola was purified on biogel P-10, fractionated on SE-Sephadex. As a result, 10 fractions of acid proteinases that differed in pH optima and activity were obtained. After purification specific activity of some fractions per 1 mg protein increased 24-32-fold. The temperature optimum of the enzymes was at 50 degrees C and pH optimum at 2.5--2.8."}
{"id": "PMID:241998", "title": "Receptor-dependent hydrolysis of cholesteryl esters contained in plasma low density lipoprotein.", "content": "Selective radioactive labeling of the cholesteryl esters contained within human plasma low density lipoprotein has allowed the study of the metabolism of these molecules in monolayers and extracts of cultured human fibroblasts. In monolayers of normal cells, binding of low density lipoprotein to its cell surface receptor was followed by rapid hydrolysis of the [3H]cholesteryl linoleate contained within the lipoprotein and accumulation of the liberated [3H]cholesterol within the cell. The stoichiometry of the degradative process suggested that the protein and cholesteryl ester components of the lipoprotein were hydrolyzed in parallel. Incubation of intact fibroblasts with chloroquine, a known inhibitor of lysosomal degradative processes, inhibited the hydrolysis of the lipoprotein-bound cholesteryl esters. Fibroblasts from subjects with the homozygous form of familial hypercholesterolemia, which lack functional low density lipoprotein receptors and thus are unable to take up this lipoprotein when it is present in the culture medium at low concentrations, were therefore unable to hydrolyze the lipoprotein-bound [3H]cholesteryl linoleate. However, cell-free extracts from these mutant cells were capable of hydrolyzing the lipoprotein-bound [3H]cholesteryl linoleate at the same rapid rate as normal cells when incubated at acid pH. These data illustrate the essential role of the low density lipoprotein receptor and of lysosomal acid hydrolases in the metabolic utilization of low density lipoproteins by cultured human fibroblasts.", "contents": "Receptor-dependent hydrolysis of cholesteryl esters contained in plasma low density lipoprotein. Selective radioactive labeling of the cholesteryl esters contained within human plasma low density lipoprotein has allowed the study of the metabolism of these molecules in monolayers and extracts of cultured human fibroblasts. In monolayers of normal cells, binding of low density lipoprotein to its cell surface receptor was followed by rapid hydrolysis of the [3H]cholesteryl linoleate contained within the lipoprotein and accumulation of the liberated [3H]cholesterol within the cell. The stoichiometry of the degradative process suggested that the protein and cholesteryl ester components of the lipoprotein were hydrolyzed in parallel. Incubation of intact fibroblasts with chloroquine, a known inhibitor of lysosomal degradative processes, inhibited the hydrolysis of the lipoprotein-bound cholesteryl esters. Fibroblasts from subjects with the homozygous form of familial hypercholesterolemia, which lack functional low density lipoprotein receptors and thus are unable to take up this lipoprotein when it is present in the culture medium at low concentrations, were therefore unable to hydrolyze the lipoprotein-bound [3H]cholesteryl linoleate. However, cell-free extracts from these mutant cells were capable of hydrolyzing the lipoprotein-bound [3H]cholesteryl linoleate at the same rapid rate as normal cells when incubated at acid pH. These data illustrate the essential role of the low density lipoprotein receptor and of lysosomal acid hydrolases in the metabolic utilization of low density lipoproteins by cultured human fibroblasts."}
{"id": "PMID:241999", "title": "ATP, cyclic AMP, and magnesium increase the affinity of rat striatal tyrosine hydroxylase for its cofactor.", "content": "Treatment of rat striatal tyrosine hydroxylase [tyrosine 3-monooxygenase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.2] with conditions optimal for protein phosphorylation results in the reduction of the tyrosine hydroxylase Km for the cofactor 6-methyltetrahydropterin from 0.50 mM to 0.16 mM. This reaction is dependent upon ATP, 3':5'-cAMP, and Mg++ and causes a marked decrease in the sensitivity to end-product inhibition. Other brain regions and the adrenal gland show a similar response.", "contents": "ATP, cyclic AMP, and magnesium increase the affinity of rat striatal tyrosine hydroxylase for its cofactor. Treatment of rat striatal tyrosine hydroxylase [tyrosine 3-monooxygenase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.2] with conditions optimal for protein phosphorylation results in the reduction of the tyrosine hydroxylase Km for the cofactor 6-methyltetrahydropterin from 0.50 mM to 0.16 mM. This reaction is dependent upon ATP, 3':5'-cAMP, and Mg++ and causes a marked decrease in the sensitivity to end-product inhibition. Other brain regions and the adrenal gland show a similar response."}
{"id": "PMID:241996", "title": "[Production and properties of a beta-galactosidase preparation from Alternaria tenuis].", "content": "Different methods of the preparation of fungal beta-galactosidase from the 72-hour culture of Alternaria tenuis were tested: lyophilization of the culture liquid, precipitation with ethanol, acetone, ammonium sulphate. Optimal results were obtained with precipitation by 1.5 acetone volume. Studies of the properties of fungal beta-galactosidase demonstrated that the preparation retained its activity during 22 month storage at 5 degrees C. The fungal preparation had pH optimum at a more acidic zone (4.2 versus 6.9), was active in a wider pH range 2.8-5.7 and 6.2-7.5), had a much higher temperature optimum (65 degrees and 30 degrees) and better thermostability as compared with the yeast preparation. Data on other properties of the preparation are presented.", "contents": "[Production and properties of a beta-galactosidase preparation from Alternaria tenuis]. Different methods of the preparation of fungal beta-galactosidase from the 72-hour culture of Alternaria tenuis were tested: lyophilization of the culture liquid, precipitation with ethanol, acetone, ammonium sulphate. Optimal results were obtained with precipitation by 1.5 acetone volume. Studies of the properties of fungal beta-galactosidase demonstrated that the preparation retained its activity during 22 month storage at 5 degrees C. The fungal preparation had pH optimum at a more acidic zone (4.2 versus 6.9), was active in a wider pH range 2.8-5.7 and 6.2-7.5), had a much higher temperature optimum (65 degrees and 30 degrees) and better thermostability as compared with the yeast preparation. Data on other properties of the preparation are presented."}
{"id": "PMID:241997", "title": "[Formation of dextranases by mycelial fungi and actinomycetes].", "content": "The dextranase activity of cultures of mycelial fungi of different genera and actinomycetes from the Chromogenes species of the Actinomyces genus was studied. About one third of the mycelial fungi and 8% of actinomycetes showed dextranase activity. The resulting extracellular dextranases demonstrated on endotypic pattern of action on the substrate. Actinomycete dextranases were several times more active than fungal dextranases and exhibited a significant activity in the neutral and weakly alkaline medium. Highly productive strains that are promising as dextranase producers were isolated.", "contents": "[Formation of dextranases by mycelial fungi and actinomycetes]. The dextranase activity of cultures of mycelial fungi of different genera and actinomycetes from the Chromogenes species of the Actinomyces genus was studied. About one third of the mycelial fungi and 8% of actinomycetes showed dextranase activity. The resulting extracellular dextranases demonstrated on endotypic pattern of action on the substrate. Actinomycete dextranases were several times more active than fungal dextranases and exhibited a significant activity in the neutral and weakly alkaline medium. Highly productive strains that are promising as dextranase producers were isolated."}
{"id": "PMID:242000", "title": "Stabilization of electron spin resonance probes for photosynthesis studies.", "content": "The major obstacle to the study of functional/structural interrelationships of spinach chloroplasts by using spin labels has been the rapid loss of the electron paramagnetic resonance (EPR) signals upon illumination with visible light. The present study demonstrates that the addition of ferredoxin and NADP+ in the presence of N-tris(hydroxymethyl)methylglycine (Tricine) buffer at pH 7.1 or higher mitigates the rapid loss of Biradical X [N,N'-bis(1-oxyl - 2,2,5,5 - tetramethylpyrroline-3-carboxy)-1,2-diaminoethane] and Monradical A (2,2,5,5-tetramethyl-3-carbamidpyrroline-1-oxyl). However, the 5-line EPR spectrum characteristic of Biradical X in aqueous solution was changed to a dominantly 3-line spectrum within a few minutes after illumination in the presence of ferredoxin and NADP+. Analysis of the double integration of the first derivative EPR spectrum revealed no decrease in Biradical X concentration for more than 30 min of illumination. Our data suggest that Biradical X attaches to some soluble macromolecule(s) and that illumination of chloroplasts promotes such an attachment.", "contents": "Stabilization of electron spin resonance probes for photosynthesis studies. The major obstacle to the study of functional/structural interrelationships of spinach chloroplasts by using spin labels has been the rapid loss of the electron paramagnetic resonance (EPR) signals upon illumination with visible light. The present study demonstrates that the addition of ferredoxin and NADP+ in the presence of N-tris(hydroxymethyl)methylglycine (Tricine) buffer at pH 7.1 or higher mitigates the rapid loss of Biradical X [N,N'-bis(1-oxyl - 2,2,5,5 - tetramethylpyrroline-3-carboxy)-1,2-diaminoethane] and Monradical A (2,2,5,5-tetramethyl-3-carbamidpyrroline-1-oxyl). However, the 5-line EPR spectrum characteristic of Biradical X in aqueous solution was changed to a dominantly 3-line spectrum within a few minutes after illumination in the presence of ferredoxin and NADP+. Analysis of the double integration of the first derivative EPR spectrum revealed no decrease in Biradical X concentration for more than 30 min of illumination. Our data suggest that Biradical X attaches to some soluble macromolecule(s) and that illumination of chloroplasts promotes such an attachment."}
{"id": "PMID:242001", "title": "Specificity of substrate recognition by the EcoRI restriction endonuclease.", "content": "The substrate specificity of the EcoRI restriction endonuclease can be varied in vitro by changing the pH and the ionic environment of the reaction. Phosphodiester bond cleavage occurs at a DNA hexanucleotide sequence d(N-G-A-A-T-T-C-N)/d(N-C-T-T-A-A-G-N) when the ionic strength is high, 100 mM Tris-HCl, 50 mM NaCl, 5 mM MgCl2, and the pH is approximately 7.3. Lowering the ionic strength to 25 mM Tris-HCl, 2 mM MgCl2, and adjusting the pH to 8.5 reduces the recognition specificity of the EcoRI endonuclease to the tetranucleotide sequence, d(N-A-A-T-T-N)/d(N-T-T-A-A-N). The enzymatic activity responsible for this substrate recognition is referred to as EcoRI. Cleavage of pVH51 plasmid DNA under EcoRI conditions results in a number of partial digest fragments, some of which disappear slowly over a prolonged digestion period. This suggests that different recognition sites are cleaved at different rates. Comparison of DNA fragment patterns of modified and unmodified pVH51 DNA indicates that the canonical EcoRI sequence is the most rapidly cleaved site under EcoRI conditions. DNA modified in vivo by the EcoRI methylase is not cleaved by the EcoRI endonuclease under standard conditions, but is cleaved under EcoRI conditions at sites other than the standard EcoRI substrate.", "contents": "Specificity of substrate recognition by the EcoRI restriction endonuclease. The substrate specificity of the EcoRI restriction endonuclease can be varied in vitro by changing the pH and the ionic environment of the reaction. Phosphodiester bond cleavage occurs at a DNA hexanucleotide sequence d(N-G-A-A-T-T-C-N)/d(N-C-T-T-A-A-G-N) when the ionic strength is high, 100 mM Tris-HCl, 50 mM NaCl, 5 mM MgCl2, and the pH is approximately 7.3. Lowering the ionic strength to 25 mM Tris-HCl, 2 mM MgCl2, and adjusting the pH to 8.5 reduces the recognition specificity of the EcoRI endonuclease to the tetranucleotide sequence, d(N-A-A-T-T-N)/d(N-T-T-A-A-N). The enzymatic activity responsible for this substrate recognition is referred to as EcoRI. Cleavage of pVH51 plasmid DNA under EcoRI conditions results in a number of partial digest fragments, some of which disappear slowly over a prolonged digestion period. This suggests that different recognition sites are cleaved at different rates. Comparison of DNA fragment patterns of modified and unmodified pVH51 DNA indicates that the canonical EcoRI sequence is the most rapidly cleaved site under EcoRI conditions. DNA modified in vivo by the EcoRI methylase is not cleaved by the EcoRI endonuclease under standard conditions, but is cleaved under EcoRI conditions at sites other than the standard EcoRI substrate."}
{"id": "PMID:242002", "title": "Redox equilibria of liganded forms of methemoglobin.", "content": "We have examined the redox equilibria of azidomethemoglobin (low-spin) and fluoromethemoglobin (high-spin). We have derived a modified Hill equation which includes the tetramer--dimer equilibrium of the oxidized form, and also generalized the two-state model to incorporate ligand binding to the ferriheme. The pH dependence of the redox Hill's constant for fluoromethemoglobin is the same as that for methemoglobin, demonstrating that this dependence and the marked cooperativity achieved (n = 2.2) are not coupled to changes of the ferriheme spin state. The redox Hill's constant for azidomethemoglobin, however, is as large as the oxygenation Hill's constant (n approximately 2.7) and is also roughly pH independent.", "contents": "Redox equilibria of liganded forms of methemoglobin. We have examined the redox equilibria of azidomethemoglobin (low-spin) and fluoromethemoglobin (high-spin). We have derived a modified Hill equation which includes the tetramer--dimer equilibrium of the oxidized form, and also generalized the two-state model to incorporate ligand binding to the ferriheme. The pH dependence of the redox Hill's constant for fluoromethemoglobin is the same as that for methemoglobin, demonstrating that this dependence and the marked cooperativity achieved (n = 2.2) are not coupled to changes of the ferriheme spin state. The redox Hill's constant for azidomethemoglobin, however, is as large as the oxygenation Hill's constant (n approximately 2.7) and is also roughly pH independent."}
{"id": "PMID:242003", "title": "Omega-aminoalkyl agaroses in the resolution of enzymes involved in regulation of glutamine metabolism.", "content": "Systematic examination of a homologous series of omega-aminoalkyl agaroses showed that the pentyl derivative (Seph-C5-NH2) was best suited for the retention and subsequent separation of several proteins involved in the regulation of glutamine metabolism in Escherichia coli, including: glutamine synthetase [EC 6.3.1.2; L-glutamate:ammonia ligase (ADP-forming)], ATP:glutamine synthetase adenylyltransferase (EC 2.7.7.42), the PII regulatory protein which regulates the adenylylation and deadenylylation activities of the adenylyltransferase, the UTP:PII protein uridylyltransferase, and the uridylyl removing enzyme which catalyzes the removal of uridylyl groups from uridylylated PII protein. Resolution of these proteins was achieved by gradually increasing the concentration of KCl in the eluant, which resulted in consecutive detachment of the proteins from the column. Proteins that co-elute from a DEAE-cellulose column can be resolved and further purified on epsilon-aminopentyl agarose, probably due to the fact that with the homologous series it is possible to adjust the contribution of hydrophobic interactions for optimal resolution.", "contents": "Omega-aminoalkyl agaroses in the resolution of enzymes involved in regulation of glutamine metabolism. Systematic examination of a homologous series of omega-aminoalkyl agaroses showed that the pentyl derivative (Seph-C5-NH2) was best suited for the retention and subsequent separation of several proteins involved in the regulation of glutamine metabolism in Escherichia coli, including: glutamine synthetase [EC 6.3.1.2; L-glutamate:ammonia ligase (ADP-forming)], ATP:glutamine synthetase adenylyltransferase (EC 2.7.7.42), the PII regulatory protein which regulates the adenylylation and deadenylylation activities of the adenylyltransferase, the UTP:PII protein uridylyltransferase, and the uridylyl removing enzyme which catalyzes the removal of uridylyl groups from uridylylated PII protein. Resolution of these proteins was achieved by gradually increasing the concentration of KCl in the eluant, which resulted in consecutive detachment of the proteins from the column. Proteins that co-elute from a DEAE-cellulose column can be resolved and further purified on epsilon-aminopentyl agarose, probably due to the fact that with the homologous series it is possible to adjust the contribution of hydrophobic interactions for optimal resolution."}
{"id": "PMID:242004", "title": "Glutamine synthetase forms three- and seven-stranded helical cables.", "content": "When cobaltous ion is bound to glutamine synthetase [L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2], the two-layered hexagonal molecules polymerize face-to-face, to form long strands. The strands then wind round each other to form three- and seven-stranded cables. The structures of these cables are not immediately evident from electron micrographs because of the confusing superposition of front and back portions of the cables. But optical diffraction and filtering by the procedure of Klug and DeRosier leads to interpretable images of the cables. Because a micrograph of the seven-stranded cable contains 24 views of the glutamine synthetase molecule, it is possible to reconstruct the three-dimensional electron density of a cable and its constituent molecules at a resolution of 30--50 A. This reconstruction confirms that the symmetry of a glutamine synthetase molecule is D6. It suggests that the single subunit is an oblate ellipsoid with its minor axis (about 48 A) roughly parallel to the 6-fold axis of the molecule and its major axis (about 63 A) perpendicular to the 6-fold axis of the molecule. The subunits of the two hexagonal layers of a molecule are eclipsed. Neighboring molecules along a strand also have their hexagonal faces together, but they are rotated about the strand axis by about 7 degrees with respect to one another, rather than being eclipsed. Six outer strands are coiled about a straight central strand, and each forms identical contacts with the central strand. Moreover, these contacts between central and outer strands are apparently similar to the contacts between neighboring outer strands.", "contents": "Glutamine synthetase forms three- and seven-stranded helical cables. When cobaltous ion is bound to glutamine synthetase [L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2], the two-layered hexagonal molecules polymerize face-to-face, to form long strands. The strands then wind round each other to form three- and seven-stranded cables. The structures of these cables are not immediately evident from electron micrographs because of the confusing superposition of front and back portions of the cables. But optical diffraction and filtering by the procedure of Klug and DeRosier leads to interpretable images of the cables. Because a micrograph of the seven-stranded cable contains 24 views of the glutamine synthetase molecule, it is possible to reconstruct the three-dimensional electron density of a cable and its constituent molecules at a resolution of 30--50 A. This reconstruction confirms that the symmetry of a glutamine synthetase molecule is D6. It suggests that the single subunit is an oblate ellipsoid with its minor axis (about 48 A) roughly parallel to the 6-fold axis of the molecule and its major axis (about 63 A) perpendicular to the 6-fold axis of the molecule. The subunits of the two hexagonal layers of a molecule are eclipsed. Neighboring molecules along a strand also have their hexagonal faces together, but they are rotated about the strand axis by about 7 degrees with respect to one another, rather than being eclipsed. Six outer strands are coiled about a straight central strand, and each forms identical contacts with the central strand. Moreover, these contacts between central and outer strands are apparently similar to the contacts between neighboring outer strands."}
{"id": "PMID:242005", "title": "31P magnetic resonance of tRNA.", "content": "We have observed well-resolved 31P resonances at 65 kG (109 MHz) in solutions of Escherichia coli tRNAGlu and yeast tRNAPhe. One resolved resonance, identified as the terminal phosphate, titrates with a pK = 6.35. Upon melting the yeast tRNAPhe in 0.1 M NaCl, without Mg++, the resolved peaks broaden and disappear in the vicinity of 35 degrees while the central cluster narrows drastically, shifts slightly, and loses its structure. Addition of Mg++ shifts one resolved peak and changes the shape of the cluster. The 31P lines are broader when observed at 65 kG than at 24 kG. The broadening is shown to come from chemical shift anisotropy which is estimated to be about 140 ppm.", "contents": "31P magnetic resonance of tRNA. We have observed well-resolved 31P resonances at 65 kG (109 MHz) in solutions of Escherichia coli tRNAGlu and yeast tRNAPhe. One resolved resonance, identified as the terminal phosphate, titrates with a pK = 6.35. Upon melting the yeast tRNAPhe in 0.1 M NaCl, without Mg++, the resolved peaks broaden and disappear in the vicinity of 35 degrees while the central cluster narrows drastically, shifts slightly, and loses its structure. Addition of Mg++ shifts one resolved peak and changes the shape of the cluster. The 31P lines are broader when observed at 65 kG than at 24 kG. The broadening is shown to come from chemical shift anisotropy which is estimated to be about 140 ppm."}
{"id": "PMID:242006", "title": "Gene transfer to human cells: transducing phage lambda plac gene expression in GMI-gangliosidosis fibroblasts.", "content": "Genetic information from the bacterium Escherichia coli was transferred to human cells by means of the specialized transducing phage lambda plac carrying the bacterial z gene for the enzyme beta-galactosidase (geta-D-galactoside galactohydrolase, EC 3.2.1.23). As recipient cells, cultured skin fibroblasts from a patient with generalized gangliosidosis (GMI-gangliosidosis Type I) characterized by a severe deficiency of beta-galactosidase activity were used. The deficient human cells were incubated with the bacteriophage lambda plac or lambda plac DNA and beta-galactosidase activity was measured in order to detect gene transfer and acceptance of the prokaryotic information in the mammalian system for transcription and translation. The expression of the phage genome in the deficient fibroblasts could be demonstrated by detection of higher beta-galactosidase activity after incubation with phage lambda plac in three out of 19 experiments and in four out of 16 experiments after treatment with lambda plac DNA. Lambda plac DNA induced much higher enzyme activities than infective phage particles. Immunochemical and physicochemical assays could not distinguish the induced beta-galactosidase activity from that of the z-gene product of E. coli.", "contents": "Gene transfer to human cells: transducing phage lambda plac gene expression in GMI-gangliosidosis fibroblasts. Genetic information from the bacterium Escherichia coli was transferred to human cells by means of the specialized transducing phage lambda plac carrying the bacterial z gene for the enzyme beta-galactosidase (geta-D-galactoside galactohydrolase, EC 3.2.1.23). As recipient cells, cultured skin fibroblasts from a patient with generalized gangliosidosis (GMI-gangliosidosis Type I) characterized by a severe deficiency of beta-galactosidase activity were used. The deficient human cells were incubated with the bacteriophage lambda plac or lambda plac DNA and beta-galactosidase activity was measured in order to detect gene transfer and acceptance of the prokaryotic information in the mammalian system for transcription and translation. The expression of the phage genome in the deficient fibroblasts could be demonstrated by detection of higher beta-galactosidase activity after incubation with phage lambda plac in three out of 19 experiments and in four out of 16 experiments after treatment with lambda plac DNA. Lambda plac DNA induced much higher enzyme activities than infective phage particles. Immunochemical and physicochemical assays could not distinguish the induced beta-galactosidase activity from that of the z-gene product of E. coli."}
{"id": "PMID:242007", "title": "Bacteriophage T4 whiskers: a rudimentary environment-sensing device.", "content": "The 400 A filaments or \"whiskers,\" which extend outward from the collar region of the phage, control retraction and extension of the tail fibers in response to certain environmental conditions. The tail fibers of normal phage retract in the absence of a required adsorption cofactor, at low pH, at low ionic strength, at low temperature, and at high concentrations of polyethylene glycol. The tail fibers of mutant whiskerless (wac) phage still retract under the first two conditions, but not the last three. Antibodies to whiskers neutralize T4, probably by fixing tail fibers in the retracted configuration. Phage with retracted tail fibers adsorb poorly to host bacterial cells, and their adsorption rate increases as the fibers become extended. These results suggest that one function of the whiskers is to retract the tail fibers and thereby prevent adsorption to host cells under certain conditions that might be unfavorable for production of phage progeny following infection.", "contents": "Bacteriophage T4 whiskers: a rudimentary environment-sensing device. The 400 A filaments or \"whiskers,\" which extend outward from the collar region of the phage, control retraction and extension of the tail fibers in response to certain environmental conditions. The tail fibers of normal phage retract in the absence of a required adsorption cofactor, at low pH, at low ionic strength, at low temperature, and at high concentrations of polyethylene glycol. The tail fibers of mutant whiskerless (wac) phage still retract under the first two conditions, but not the last three. Antibodies to whiskers neutralize T4, probably by fixing tail fibers in the retracted configuration. Phage with retracted tail fibers adsorb poorly to host bacterial cells, and their adsorption rate increases as the fibers become extended. These results suggest that one function of the whiskers is to retract the tail fibers and thereby prevent adsorption to host cells under certain conditions that might be unfavorable for production of phage progeny following infection."}
{"id": "PMID:242008", "title": "Titration of sodium channels in canine gastric mucosa.", "content": "Net Na+ flux from mucosa to lumen, potential difference, and volume and plasma protein outputs were measured in vagally denervated, separated pouches of the dog's oxyntic or pyloric glandular mucosa when the pouches were irrigated with Na+-free solutions whose pH ranged from 1.5 to 12.2. The apparent permeability to Na+(P'Na) was calculated. P'Na is lowest when the mucosa is bathed with acid and increases 2- to 3-fold when the pH is raised to 10. In the range of pH 10.0--11.2 P'Na is greater by an order of magnitude, but volume output is small, and no plasma proteins are shed. When the pH is above 11.2 there is an abrupt increase in P'Na, and the mucosa sheds a large volume of fluid containing plasma proteins. The change effected by raising the pH to the range of 10.0--11.2 occurs within 10 sec, and it is reversible. The change effected by raising the pH above 11.2 also occurs within 10 sec, and it is partly reversible.", "contents": "Titration of sodium channels in canine gastric mucosa. Net Na+ flux from mucosa to lumen, potential difference, and volume and plasma protein outputs were measured in vagally denervated, separated pouches of the dog's oxyntic or pyloric glandular mucosa when the pouches were irrigated with Na+-free solutions whose pH ranged from 1.5 to 12.2. The apparent permeability to Na+(P'Na) was calculated. P'Na is lowest when the mucosa is bathed with acid and increases 2- to 3-fold when the pH is raised to 10. In the range of pH 10.0--11.2 P'Na is greater by an order of magnitude, but volume output is small, and no plasma proteins are shed. When the pH is above 11.2 there is an abrupt increase in P'Na, and the mucosa sheds a large volume of fluid containing plasma proteins. The change effected by raising the pH to the range of 10.0--11.2 occurs within 10 sec, and it is reversible. The change effected by raising the pH above 11.2 also occurs within 10 sec, and it is partly reversible."}
{"id": "PMID:242012", "title": "Influence of olfactory bulbectomy and the serotonergic system upon intermale aggression and maternal behavior in the mouse.", "content": "Biochemical parameters in the brains of olfactory bulbectomized male and female mice were studied in two experiments, followed by three experiments in which 5-HTP was injected into bulbectomized males and females to try to block abnormal behaviors. In Experiment 1 bulbectomized male and female mice had significantly less tryptophan hydroxylase in their brains than did sham controls. Neither 5-hydroxtryptophan decarboxylase nor tyrosine hydroxylase activity was affected. In Experiment 2 the rate of synthesis of 5-HT was significantly less in bulbectomized males and females. Since bulbectomy leads to increased pup killing by female mice, the objective of Experiments 3 and 4 was to see whether the injection of 5-HTP into bulbectomized females could block this behavior. The incidence of pup killing was not influenced, but in both studies the latency to kill was significantly prolonged. Olfactory bulbectomy eliminates aggressive behavior in male mice, and the purpose of Experiment 5 was to determine whether 5-HTP treatment could restore normal levels of aggression. No significant effect was found. The data suggest that a dual mechanism is needed to explain the behavioral abnomalities seen in the two sexes; the mechanism in the female appears to be serotonergic while that in the male is still unknown.", "contents": "Influence of olfactory bulbectomy and the serotonergic system upon intermale aggression and maternal behavior in the mouse. Biochemical parameters in the brains of olfactory bulbectomized male and female mice were studied in two experiments, followed by three experiments in which 5-HTP was injected into bulbectomized males and females to try to block abnormal behaviors. In Experiment 1 bulbectomized male and female mice had significantly less tryptophan hydroxylase in their brains than did sham controls. Neither 5-hydroxtryptophan decarboxylase nor tyrosine hydroxylase activity was affected. In Experiment 2 the rate of synthesis of 5-HT was significantly less in bulbectomized males and females. Since bulbectomy leads to increased pup killing by female mice, the objective of Experiments 3 and 4 was to see whether the injection of 5-HTP into bulbectomized females could block this behavior. The incidence of pup killing was not influenced, but in both studies the latency to kill was significantly prolonged. Olfactory bulbectomy eliminates aggressive behavior in male mice, and the purpose of Experiment 5 was to determine whether 5-HTP treatment could restore normal levels of aggression. No significant effect was found. The data suggest that a dual mechanism is needed to explain the behavioral abnomalities seen in the two sexes; the mechanism in the female appears to be serotonergic while that in the male is still unknown."}
{"id": "PMID:242013", "title": "MSH affects regional perfusion of the brain.", "content": "With the single exception of the occipital cortex, the flow of blood to most regions of the brains of conscious, unrestrained rats was reduced within 10 min after intravenous administration of alphaMSH. Though these effects were transitory for most regions of the brain, perfusion of cerebellum, pons and medulla, hippocampus, and parietal cortex was still significantly low by 20 min. Assuming that flow changes reflect functional changes, these early responses to alphaMSH suggest an explanation for the effects of this hormone in which visual learning is improved.", "contents": "MSH affects regional perfusion of the brain. With the single exception of the occipital cortex, the flow of blood to most regions of the brains of conscious, unrestrained rats was reduced within 10 min after intravenous administration of alphaMSH. Though these effects were transitory for most regions of the brain, perfusion of cerebellum, pons and medulla, hippocampus, and parietal cortex was still significantly low by 20 min. Assuming that flow changes reflect functional changes, these early responses to alphaMSH suggest an explanation for the effects of this hormone in which visual learning is improved."}
{"id": "PMID:242014", "title": "Radioautographic localization of radioactivity in rat brain after intraventricular or intracarotid injection of 3H-L-prolyl-L-leucyl glycinamide.", "content": "Tritiated L-prolyl-L-leucyl-glycinamide was injected into the carotid artery or lateral ventricle of rats and the radioactivity localized by radioautography. After intracarotid administration, the radioactivity labeled the meninges, ependymal cells bordering the ventricles, and cells of the choroid plexus, as well as the median eminence and subfornical organ and thus may have reached the cerebrospinal fluid. After intraventricular injection, globus pallidus, indusium griseum, hippocampus, corpus callosum, and meninges. The results after intracarotid injection suggest that L-prolyl-L-leucyl-glycinamide may cross the blood brain barrier and the results after intraventricular injection suggest sites of localization which might be correlated with the previously reported effects of the tripeptide on the brain.", "contents": "Radioautographic localization of radioactivity in rat brain after intraventricular or intracarotid injection of 3H-L-prolyl-L-leucyl glycinamide. Tritiated L-prolyl-L-leucyl-glycinamide was injected into the carotid artery or lateral ventricle of rats and the radioactivity localized by radioautography. After intracarotid administration, the radioactivity labeled the meninges, ependymal cells bordering the ventricles, and cells of the choroid plexus, as well as the median eminence and subfornical organ and thus may have reached the cerebrospinal fluid. After intraventricular injection, globus pallidus, indusium griseum, hippocampus, corpus callosum, and meninges. The results after intracarotid injection suggest that L-prolyl-L-leucyl-glycinamide may cross the blood brain barrier and the results after intraventricular injection suggest sites of localization which might be correlated with the previously reported effects of the tripeptide on the brain."}
{"id": "PMID:242015", "title": "Early behavioral and catecholaminergic effects of 6-hydroxydopamine and guanethidine in the neonatal rat.", "content": "New born rats received 7 consecutive daily injections of 6-hydroxydopamine (6-OHDA) or guanethidine. Locomotor activity, measured at 3 day intervals, was differentially affected by these drugs, although neither drug elimination a characteristic pattern of ontogeny of locomotor activity. Differing neurochemical effects were also observed. 6-OHDA decreased tyrosine hydroxylase activity in cortex and cerebellum, increased it in the brainstem and had no effect on the hypothalamus. Guanethidine slightly elevated enzyme levels in all four brain regions, with the elevation in brainstem significant at 16 days of age. Regional brain changes in enzyme activity after 4 daily 6-OHDA injections beginning at 1, 5 or 9 days of age indicated that toxic effect of 6-OHDA upon catecholaminergic neurons was age dependent. These data are not consistent with a simple interpretation either in terms of maturational changes in blood brain barrier permeability to 6-OHDA or neuronal uptake of the drug. Further analyses of brainstem areas indicated that the increased brainstem enzyme activity after 6-OHDA was restricted to the pons.", "contents": "Early behavioral and catecholaminergic effects of 6-hydroxydopamine and guanethidine in the neonatal rat. New born rats received 7 consecutive daily injections of 6-hydroxydopamine (6-OHDA) or guanethidine. Locomotor activity, measured at 3 day intervals, was differentially affected by these drugs, although neither drug elimination a characteristic pattern of ontogeny of locomotor activity. Differing neurochemical effects were also observed. 6-OHDA decreased tyrosine hydroxylase activity in cortex and cerebellum, increased it in the brainstem and had no effect on the hypothalamus. Guanethidine slightly elevated enzyme levels in all four brain regions, with the elevation in brainstem significant at 16 days of age. Regional brain changes in enzyme activity after 4 daily 6-OHDA injections beginning at 1, 5 or 9 days of age indicated that toxic effect of 6-OHDA upon catecholaminergic neurons was age dependent. These data are not consistent with a simple interpretation either in terms of maturational changes in blood brain barrier permeability to 6-OHDA or neuronal uptake of the drug. Further analyses of brainstem areas indicated that the increased brainstem enzyme activity after 6-OHDA was restricted to the pons."}
{"id": "PMID:242020", "title": "Studies on accumulation of (14C)-mescaline in brain homogenates: effects of psychotropic and other agents.", "content": "Incubation of rat brain homogenates or 14,500 g pellet isolated from the homogenate with (14C)-mescaline was associated with accumulation of (14C)-mescaline in the pellet. 1.33 mumol/ml of chlorpromazine, trifluoperazine, fluphenazine, imipramine, desmethylimipramine, nortriptyline and amitriptyline inhibited the accumulation of mescaline. Lower concentrations (0.133-0.44 mumol/ml) of the psychotropic drugs were less effective. The tricyclic antidepressants were less potent than the tranquilizers. Although the trimethoxyphenylacetic acid (TMPA) levels of the pellet were also reduced by the psychotropic drugs, the TMPA:mescaline ratios were unchanged indicating that the drugs had no effect on the metabolism of mescaline. The inhibition of accumulation of mescaline by the high concentrations of tranquilizers may divert more of the hallucinogen to the receptor site. Thus, an explanation for the reported worsening of clinical syndrome of hallucinogenic poisoning by tranquilizers is provided.", "contents": "Studies on accumulation of (14C)-mescaline in brain homogenates: effects of psychotropic and other agents. Incubation of rat brain homogenates or 14,500 g pellet isolated from the homogenate with (14C)-mescaline was associated with accumulation of (14C)-mescaline in the pellet. 1.33 mumol/ml of chlorpromazine, trifluoperazine, fluphenazine, imipramine, desmethylimipramine, nortriptyline and amitriptyline inhibited the accumulation of mescaline. Lower concentrations (0.133-0.44 mumol/ml) of the psychotropic drugs were less effective. The tricyclic antidepressants were less potent than the tranquilizers. Although the trimethoxyphenylacetic acid (TMPA) levels of the pellet were also reduced by the psychotropic drugs, the TMPA:mescaline ratios were unchanged indicating that the drugs had no effect on the metabolism of mescaline. The inhibition of accumulation of mescaline by the high concentrations of tranquilizers may divert more of the hallucinogen to the receptor site. Thus, an explanation for the reported worsening of clinical syndrome of hallucinogenic poisoning by tranquilizers is provided."}
{"id": "PMID:242023", "title": "Urinary purine levels in suicide.", "content": "A high-resolution liquid chromatographic system was utilized to analyze urine samples of twelve nonchemical suicide victims for the relative composition of ultraviolet-absorbing compounds. The analyses demonstrated a decrease in the output of uric acid, characteristic of severe depression, and an increase in the excretion of hypoxanthine. The excretion of 7-methylxanthine was found to be variable and xanthine was normal.", "contents": "Urinary purine levels in suicide. A high-resolution liquid chromatographic system was utilized to analyze urine samples of twelve nonchemical suicide victims for the relative composition of ultraviolet-absorbing compounds. The analyses demonstrated a decrease in the output of uric acid, characteristic of severe depression, and an increase in the excretion of hypoxanthine. The excretion of 7-methylxanthine was found to be variable and xanthine was normal."}
{"id": "PMID:242024", "title": "A comparison of the behaviour of human adult and foetal haemoglobins on oxidation.", "content": "The measurements of oxidation-reduction potentials at pH 7.0 and ionic strength of 0.1 revealed only a slight difference between human adult (HbA) and foetal haemoglobin (HbF) (161 and 145 mV), which  disappeared on increasing the ionic strength to 2.1. Kinetic data for the reactions with potassium ferricyanide and sodium nitrite of both haemoglobins in oxy- and carbonmonoxi-forms are presented at different excessive molar concentrations of oxidizing agents, in different environments at pH 7.0 and temperature ranging from 10--30 degrees C. The rate of HbF oxidation was considerably higher with both agents, despite vast differences in the reaction mechanisms.", "contents": "A comparison of the behaviour of human adult and foetal haemoglobins on oxidation. The measurements of oxidation-reduction potentials at pH 7.0 and ionic strength of 0.1 revealed only a slight difference between human adult (HbA) and foetal haemoglobin (HbF) (161 and 145 mV), which  disappeared on increasing the ionic strength to 2.1. Kinetic data for the reactions with potassium ferricyanide and sodium nitrite of both haemoglobins in oxy- and carbonmonoxi-forms are presented at different excessive molar concentrations of oxidizing agents, in different environments at pH 7.0 and temperature ranging from 10--30 degrees C. The rate of HbF oxidation was considerably higher with both agents, despite vast differences in the reaction mechanisms."}
{"id": "PMID:242028", "title": "On the significance of the increase in homovanillic acid (HVA) caused by antipsychotic drugs in corpus striatum and limbic forebrain.", "content": "The effect of various antipsychotic drugs on the blockade of dopaminergic receptors in striatum and limbic forebrain was examined by establishing dose-response curves for the increase in HVA and for the antagonism of d-amphetamine-induced rotation in rats with unilateral lesions of the substantia nigra. A good quantitative correlation was found between dopaminergic blockade in the striatum as reflected by the ED100 for striatal HVA increase and the ED50 for rotational antagonism and the occurrence of extrapyramidal side effects in man. The ED100 for the increase in HVA in the limbic forebrain showed the same rank order of potency as those in the striatum: Haloperidol greater than primozide greater than chlorpromazine greater than thioridazine greater than clozapine. The results thus demonstrate a very good correlation between the degree of dopaminergic blockade and the increase of extrapyramidal side effects in man, but suggest the possibility of a dissociation between dopaminergic blockade and antipsychotic activity.", "contents": "On the significance of the increase in homovanillic acid (HVA) caused by antipsychotic drugs in corpus striatum and limbic forebrain. The effect of various antipsychotic drugs on the blockade of dopaminergic receptors in striatum and limbic forebrain was examined by establishing dose-response curves for the increase in HVA and for the antagonism of d-amphetamine-induced rotation in rats with unilateral lesions of the substantia nigra. A good quantitative correlation was found between dopaminergic blockade in the striatum as reflected by the ED100 for striatal HVA increase and the ED50 for rotational antagonism and the occurrence of extrapyramidal side effects in man. The ED100 for the increase in HVA in the limbic forebrain showed the same rank order of potency as those in the striatum: Haloperidol greater than primozide greater than chlorpromazine greater than thioridazine greater than clozapine. The results thus demonstrate a very good correlation between the degree of dopaminergic blockade and the increase of extrapyramidal side effects in man, but suggest the possibility of a dissociation between dopaminergic blockade and antipsychotic activity."}
{"id": "PMID:242029", "title": "Neurochemical evidence for tryptaminergic ascending and descending pathways in the spinal cord of the dog.", "content": "The brain and spinal cord of the chronic spinal dog contained higher levels of tryptamine than comparable regions of the intact dog. The most significant brain elevations were found in the cerebellum and mesencephalon. Further, tryptamine in the white matter of the spinal cord above the level of transection was higher than below. These findings have been interpreted as indicating that there are tryptaminergic pathways descending in the white matter of the spinal cord from the mesencephalon, cerebellum and rostral spinal cord. The level of tryptamine below the transection was not different from that found in the intact dog, suggesting that there are not only descending but ascending tryptaminergic pathways and that when the axons are transected. tryptamine accumulates proximal to the level of transection.", "contents": "Neurochemical evidence for tryptaminergic ascending and descending pathways in the spinal cord of the dog. The brain and spinal cord of the chronic spinal dog contained higher levels of tryptamine than comparable regions of the intact dog. The most significant brain elevations were found in the cerebellum and mesencephalon. Further, tryptamine in the white matter of the spinal cord above the level of transection was higher than below. These findings have been interpreted as indicating that there are tryptaminergic pathways descending in the white matter of the spinal cord from the mesencephalon, cerebellum and rostral spinal cord. The level of tryptamine below the transection was not different from that found in the intact dog, suggesting that there are not only descending but ascending tryptaminergic pathways and that when the axons are transected. tryptamine accumulates proximal to the level of transection."}
{"id": "PMID:242030", "title": "[Controlled research of the influence of Neoston on tracking performance, heart rate, sinus arrhythmia and on subjective rating of healthy subjects].", "content": "The influence of Neoston--a relatively new analgesic, antipyretic, and anti-inflammatory agent--on performance in different tracking tests, on heart rate, on sinus arrhythmia and on subjective rating was objectivated. 15 healthy male and female subjects, aged from 19 to 27 years, took part in the sessions lasting about 2 1/2 hrs each. Two times two pills Neoston or a placebo were taken orally 2 and 5 hrs before the tests, making a total of 2 g. Performance in tracking was poorer on the whole with Neoston than with placebo, but only up to a maximum of 5%. Except one measurement point out of 10 all differences between the tests with the active drug and placebo were not statistically significant at the level of 5%. Yet a relatively uniform trend suggests a certain but only a small damping effect of Neoston. When relating the data of the second and third session on the data of the first session of each day, damping effects could be made more obvious. Hereby the influence of Neoston on tracking performance could be demonstrated to exist also statistically significant but to be practically almost irrelevant. In physiological variables as well as in subjective rating only small differences between the drug and placebo condition were measured. When relating the results to comparable research on the effects of alcohol, tranquilizers and stimulants, it is concluded that with Neoston in the relatively high dosage as used here, no real detrimental effects on traffic safety are to be expected.", "contents": "[Controlled research of the influence of Neoston on tracking performance, heart rate, sinus arrhythmia and on subjective rating of healthy subjects]. The influence of Neoston--a relatively new analgesic, antipyretic, and anti-inflammatory agent--on performance in different tracking tests, on heart rate, on sinus arrhythmia and on subjective rating was objectivated. 15 healthy male and female subjects, aged from 19 to 27 years, took part in the sessions lasting about 2 1/2 hrs each. Two times two pills Neoston or a placebo were taken orally 2 and 5 hrs before the tests, making a total of 2 g. Performance in tracking was poorer on the whole with Neoston than with placebo, but only up to a maximum of 5%. Except one measurement point out of 10 all differences between the tests with the active drug and placebo were not statistically significant at the level of 5%. Yet a relatively uniform trend suggests a certain but only a small damping effect of Neoston. When relating the data of the second and third session on the data of the first session of each day, damping effects could be made more obvious. Hereby the influence of Neoston on tracking performance could be demonstrated to exist also statistically significant but to be practically almost irrelevant. In physiological variables as well as in subjective rating only small differences between the drug and placebo condition were measured. When relating the results to comparable research on the effects of alcohol, tranquilizers and stimulants, it is concluded that with Neoston in the relatively high dosage as used here, no real detrimental effects on traffic safety are to be expected."}
{"id": "PMID:242031", "title": "The actions of flunitrazepam (Rohypnol) on heart and respiratory rates and skin potential fluctuations during the sleep cycle in normal volunteers and neurotic patients with insomnia.", "content": "The actions of flunitrazepam (Rohypnol) were assessed on the sleep cycle, heart and respiratory rates and skin potential fluctuations of normal volunteers and neurotic patients with insomnia by means of all night recordings. The most conspicuous effect of flunitrazepam (2 mg p.o.) in the healthy subject's sleep cycle was an increase of the latency for the appearance of the first REM period. In the insomniacs the compounds was effective in inducing and maintaining sleep. Flunitrazepam diminished heart rates during the REM phases and significantly decreased the variability indices, this effect being more prominent in the normal subjects. Skin potential fluctuations during stages 2 and REM sleep were also decreased although tolerance developed rapidly in this connection.", "contents": "The actions of flunitrazepam (Rohypnol) on heart and respiratory rates and skin potential fluctuations during the sleep cycle in normal volunteers and neurotic patients with insomnia. The actions of flunitrazepam (Rohypnol) were assessed on the sleep cycle, heart and respiratory rates and skin potential fluctuations of normal volunteers and neurotic patients with insomnia by means of all night recordings. The most conspicuous effect of flunitrazepam (2 mg p.o.) in the healthy subject's sleep cycle was an increase of the latency for the appearance of the first REM period. In the insomniacs the compounds was effective in inducing and maintaining sleep. Flunitrazepam diminished heart rates during the REM phases and significantly decreased the variability indices, this effect being more prominent in the normal subjects. Skin potential fluctuations during stages 2 and REM sleep were also decreased although tolerance developed rapidly in this connection."}
{"id": "PMID:242032", "title": "Self-administration of CNS stimulants by dog.", "content": "Drug-naive dogs were trained to respond for intravenous infusions of either d-amphetamine, phenmetrazine, or methylphenidate until a stable response rate per 4-hr daily session was achieved. The magnitude of reinforcement (i.e., mg/kg/infusion) was then varied systematically across a wide range for each drug. An inverse relationship between unit dose and number of self-administered infusions per session was seen. Thus, total drug intake per session remained relatively constant and was independent of unit dose. Using a parallel line bioassay design, the relative potencies of d-amphetamine, phenmetrazine, and methylphenidate to maintain self-administration were estimated. By comparing the unit doses of d-amphetamine which yielded the same rate of self-administration it was found that 1 mg of phenmetrazine is equivalent to 0.1 mg of d-amphetamine. It was also determined that 1 mg of methylphenidate is equivalent to 0.75 mg of d-amphetamine. These data indicate the dog can be used to assess the reinforcing properties of psychomotor stimulants.", "contents": "Self-administration of CNS stimulants by dog. Drug-naive dogs were trained to respond for intravenous infusions of either d-amphetamine, phenmetrazine, or methylphenidate until a stable response rate per 4-hr daily session was achieved. The magnitude of reinforcement (i.e., mg/kg/infusion) was then varied systematically across a wide range for each drug. An inverse relationship between unit dose and number of self-administered infusions per session was seen. Thus, total drug intake per session remained relatively constant and was independent of unit dose. Using a parallel line bioassay design, the relative potencies of d-amphetamine, phenmetrazine, and methylphenidate to maintain self-administration were estimated. By comparing the unit doses of d-amphetamine which yielded the same rate of self-administration it was found that 1 mg of phenmetrazine is equivalent to 0.1 mg of d-amphetamine. It was also determined that 1 mg of methylphenidate is equivalent to 0.75 mg of d-amphetamine. These data indicate the dog can be used to assess the reinforcing properties of psychomotor stimulants."}
{"id": "PMID:242035", "title": "The composition and flow of parotid saliva during acute hyperkalaemia in sodium-deficient sheep.", "content": "Sheep were infused intravenously with 0-43 M-KCl at 2 ml/min for 2 hr while they were either sodium-replete or sodium-deficient after the unilateral loss of parotid saliva for 18 hr or 3 days. Salivary flow was depressed during potassium infusion and the flow rates observed at maximum hyperkalaemia were similar in all three states of sodium balance despite the large differences in flow rate before potassium infusion. The fall in salivary Na/K ratio during potassium administration was diphasic, the initial decline being slow and followed by a more rapid fall in the ratio. The duration of the initial period of slow decline in this ratio ranged from 75-105 min, 45-60 min, and about 15 min in the sodium-replete, mildly sodium-deficient and severely sodium-deficient states respectively. The decline in salivary flow during sodium depletion was associated with decreasing salivary bicarbonate concentration and increasing salivary phosphate and hydrogen ion concentrations with the concentration of chloride showing no consistent trend. During acute hyperkalaemia the chloride and phosphate concentrations were negatively correlated with salivary flow, the bicarbonate concentration was positively correlated with flow and the hydrogen ion concentration was unaltered. The sodium concentration of the saliva showed a statistically significant correlation with flow only when the sheep were severely sodium-deficient.", "contents": "The composition and flow of parotid saliva during acute hyperkalaemia in sodium-deficient sheep. Sheep were infused intravenously with 0-43 M-KCl at 2 ml/min for 2 hr while they were either sodium-replete or sodium-deficient after the unilateral loss of parotid saliva for 18 hr or 3 days. Salivary flow was depressed during potassium infusion and the flow rates observed at maximum hyperkalaemia were similar in all three states of sodium balance despite the large differences in flow rate before potassium infusion. The fall in salivary Na/K ratio during potassium administration was diphasic, the initial decline being slow and followed by a more rapid fall in the ratio. The duration of the initial period of slow decline in this ratio ranged from 75-105 min, 45-60 min, and about 15 min in the sodium-replete, mildly sodium-deficient and severely sodium-deficient states respectively. The decline in salivary flow during sodium depletion was associated with decreasing salivary bicarbonate concentration and increasing salivary phosphate and hydrogen ion concentrations with the concentration of chloride showing no consistent trend. During acute hyperkalaemia the chloride and phosphate concentrations were negatively correlated with salivary flow, the bicarbonate concentration was positively correlated with flow and the hydrogen ion concentration was unaltered. The sodium concentration of the saliva showed a statistically significant correlation with flow only when the sheep were severely sodium-deficient."}
{"id": "PMID:242043", "title": "Characterization of soluble and microsomal adenosine 3',5'-monophosphate-dependent protein kinases from rabbit heart.", "content": "Cardiac microsomes contained an intrinsic adenosine 3',5'-monophosphate (cyclic AMP)-dependent protein kinase which stimulated phosphorylation of serine residue(s) of microsomal protein. The phosphorylated residues were associated with a microsomal protein component of 20,000 molecular weight as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Intrinsic phosphoprotein phosphatase activity of the microsomal membrane resulted in rapid dephosphorylation of these residues. Microsomes phosphorylated in the presence of cyclic AMP (10(-6) M) exhibited enhanced calcium uptake. We conclude that: 1) cardiac microsomes contain intrinsic cyclic AMP-dependent protein kinase(s) which phosphorylate a specific microsomal protein and phosphoprotein phosphatase(s) capable of dephosphorylating this protein, 2) phosphorylation of this protein enhances calcium uptake, 3) reversible phosphorylation of microsomal membrane may be an important mechanism for the regulation of calcium uptake of cardiac microsomes by cyclic AMP.", "contents": "Characterization of soluble and microsomal adenosine 3',5'-monophosphate-dependent protein kinases from rabbit heart. Cardiac microsomes contained an intrinsic adenosine 3',5'-monophosphate (cyclic AMP)-dependent protein kinase which stimulated phosphorylation of serine residue(s) of microsomal protein. The phosphorylated residues were associated with a microsomal protein component of 20,000 molecular weight as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Intrinsic phosphoprotein phosphatase activity of the microsomal membrane resulted in rapid dephosphorylation of these residues. Microsomes phosphorylated in the presence of cyclic AMP (10(-6) M) exhibited enhanced calcium uptake. We conclude that: 1) cardiac microsomes contain intrinsic cyclic AMP-dependent protein kinase(s) which phosphorylate a specific microsomal protein and phosphoprotein phosphatase(s) capable of dephosphorylating this protein, 2) phosphorylation of this protein enhances calcium uptake, 3) reversible phosphorylation of microsomal membrane may be an important mechanism for the regulation of calcium uptake of cardiac microsomes by cyclic AMP."}
{"id": "PMID:242039", "title": "[The value of non-specific general therapy of shock caused by acute pancreatitis].", "content": "The shock in general, including that of acute pancreatitis, presents, according to our conception, as an energetic disease involving primarily the cell (by the intensive catabolic processes induced by the pancreatic lesion) and secondarily the most peripheral and mobile sector, that of the hemodynamic compartment. There is no etiological treatment of pancreatitis (the exceptions are very rare), and this is the reason for which we adopt a conservative attitude, and medical treatment, in the acute stage of the disease. The basic treatment of the shock of acute pancreatitis is considered to be the re-establishment of the circulatory volume with the aid of non-colloidal isotonic solutions that are given in large amounts (8-17 liters in a 24-hour period) under continuous perfusion. This technique is called hyperhydration or transrenal dialysis. Making use of this technique in the treatment of shock occurring in the course of acute pancreatitis the death-rate recorded was as low as 2,3% and the number of complications was very low.", "contents": "[The value of non-specific general therapy of shock caused by acute pancreatitis]. The shock in general, including that of acute pancreatitis, presents, according to our conception, as an energetic disease involving primarily the cell (by the intensive catabolic processes induced by the pancreatic lesion) and secondarily the most peripheral and mobile sector, that of the hemodynamic compartment. There is no etiological treatment of pancreatitis (the exceptions are very rare), and this is the reason for which we adopt a conservative attitude, and medical treatment, in the acute stage of the disease. The basic treatment of the shock of acute pancreatitis is considered to be the re-establishment of the circulatory volume with the aid of non-colloidal isotonic solutions that are given in large amounts (8-17 liters in a 24-hour period) under continuous perfusion. This technique is called hyperhydration or transrenal dialysis. Making use of this technique in the treatment of shock occurring in the course of acute pancreatitis the death-rate recorded was as low as 2,3% and the number of complications was very low."}
{"id": "PMID:242044", "title": "Observations on the interaction of calcium and hydrogen ions on ATP hydrolysis by the contractile elements of cardiac muscle.", "content": "The ability of cardiac myosin, actomyosin, and myofibrils to hydrolyze ATP has been studied at varying hydrogen and calcium ion concentrations. The ATPase activity of dog cardiac myofibrils was measured over the pH range of 6.5-7.4, as the calcium ion concentration was varied from 0-1.5 X 10(-4) M. The ATPase of these myofibrils, and of rabbit cardiac myosin and actomyosin was also measured in the absence of ionic calcium over the pH range 6-9. The Km of MgATP of cardiac myofibrils was studied over the pH range 6.5-7.4. In the absence of calcium ions, myofibrillar, myosin, and actomyosin ATPase activities are maximal at pH 8.0. At any given calcium ion concentration, the myofibrillar ATPase is depressed by lowering pH. The results suggest that the influence of hydrogen ions on the ability of myofibrils to hydrolyze ATP is complex, and may not only be the result of a simple competition between hydrogen and calcium ions for binding sites on troponin.", "contents": "Observations on the interaction of calcium and hydrogen ions on ATP hydrolysis by the contractile elements of cardiac muscle. The ability of cardiac myosin, actomyosin, and myofibrils to hydrolyze ATP has been studied at varying hydrogen and calcium ion concentrations. The ATPase activity of dog cardiac myofibrils was measured over the pH range of 6.5-7.4, as the calcium ion concentration was varied from 0-1.5 X 10(-4) M. The ATPase of these myofibrils, and of rabbit cardiac myosin and actomyosin was also measured in the absence of ionic calcium over the pH range 6-9. The Km of MgATP of cardiac myofibrils was studied over the pH range 6.5-7.4. In the absence of calcium ions, myofibrillar, myosin, and actomyosin ATPase activities are maximal at pH 8.0. At any given calcium ion concentration, the myofibrillar ATPase is depressed by lowering pH. The results suggest that the influence of hydrogen ions on the ability of myofibrils to hydrolyze ATP is complex, and may not only be the result of a simple competition between hydrogen and calcium ions for binding sites on troponin."}
{"id": "PMID:242045", "title": "The effect of temperature and mechanical work load on the intracellular pH and buffer capacity of cardiac muscle in rats.", "content": "The effect of temperature on hydrogen ions and buffer capacity in extracellular fluid differs from the effects in intracellular fluid. In our experiments cardiac hypertrophy was achieved by increasing the mechanical work load. It could be demonstrated that there is a certain correlation between buffering of hydrogen ions and mechanical activity of heart muscle.", "contents": "The effect of temperature and mechanical work load on the intracellular pH and buffer capacity of cardiac muscle in rats. The effect of temperature on hydrogen ions and buffer capacity in extracellular fluid differs from the effects in intracellular fluid. In our experiments cardiac hypertrophy was achieved by increasing the mechanical work load. It could be demonstrated that there is a certain correlation between buffering of hydrogen ions and mechanical activity of heart muscle."}
{"id": "PMID:242046", "title": "Effect of H+ on force development of the heart muscle under acute respiratory failure by cyanide.", "content": "Force decay of slowly paced (12/min) isometric ventricular strips of frog heart at low temperature (+12 degrees C) was studied under standard cellular respiratory failure (3 mM NaCN). An exponential force decay obtained at pH0 6.0 was transformed to two-step decline by increasing the pH0. The rapid phase of the force decline was pH insensitive. The slope of the second slow phase was regulated by pH0 between 6.0 and 7.7 (force reduction to 50 percent was 7 min at pH 6.0 and more than 60 min at 7.7). This effect was partially blocked by citrate (1.5-3.0 mM). Data obtained are compared with pH values measured within the normal and ischemic myocardium and are discussed with respect to the role of proton accumulation and diffusion within the ischemic ventricular wall.", "contents": "Effect of H+ on force development of the heart muscle under acute respiratory failure by cyanide. Force decay of slowly paced (12/min) isometric ventricular strips of frog heart at low temperature (+12 degrees C) was studied under standard cellular respiratory failure (3 mM NaCN). An exponential force decay obtained at pH0 6.0 was transformed to two-step decline by increasing the pH0. The rapid phase of the force decline was pH insensitive. The slope of the second slow phase was regulated by pH0 between 6.0 and 7.7 (force reduction to 50 percent was 7 min at pH 6.0 and more than 60 min at 7.7). This effect was partially blocked by citrate (1.5-3.0 mM). Data obtained are compared with pH values measured within the normal and ischemic myocardium and are discussed with respect to the role of proton accumulation and diffusion within the ischemic ventricular wall."}
{"id": "PMID:242047", "title": "Calcium binding to cardiac sarcolemma.", "content": "Studies with a sarcolemma preparation from guinea pig hearts revealed two classes of Ca2+ binding sites: high affinity sites (Km' of 16 muM) and a 10-fold greater number of low affinity sites (Km' of 800 muM). Low affinity Ca2+ binding was inhibited by ruthenium red and verapamil, suggesting that these sites are located on the external side of the membrane. However, clear-cut competition between H+ and Ca2+ could not be demonstrated with isolated sarcolemma.", "contents": "Calcium binding to cardiac sarcolemma. Studies with a sarcolemma preparation from guinea pig hearts revealed two classes of Ca2+ binding sites: high affinity sites (Km' of 16 muM) and a 10-fold greater number of low affinity sites (Km' of 800 muM). Low affinity Ca2+ binding was inhibited by ruthenium red and verapamil, suggesting that these sites are located on the external side of the membrane. However, clear-cut competition between H+ and Ca2+ could not be demonstrated with isolated sarcolemma."}
{"id": "PMID:242048", "title": "Labilization of lysosomes and mitochondria in situ by hypoxia and hypoxia-related factors.", "content": "Primary cultures of rat heart muscle and endothelioid cells were used to study the labilization of lysosomes and mitochondria by hypoxia, \"hypoxia substitutes\", and the in vivo-related factors of free fatty acid and pH. Subliminally-active levels tested were: hypoxia (1% O2/4 days), 5x10(-6)M sodium stearate: albumin in 6:1 ratio/30 min, KCN (1x10(-3)M/1 hr), 2 deoxy-glucose (3x10(-2)M/12 hr), acidosis (pH 6.9/30 min) and combinations. KCN plus 2-DG labilized the organelles in both cell types. Sensitivity to injury was in the order mitochondria greater than lysosomes and muscle cells greater than endothelioid cells.", "contents": "Labilization of lysosomes and mitochondria in situ by hypoxia and hypoxia-related factors. Primary cultures of rat heart muscle and endothelioid cells were used to study the labilization of lysosomes and mitochondria by hypoxia, \"hypoxia substitutes\", and the in vivo-related factors of free fatty acid and pH. Subliminally-active levels tested were: hypoxia (1% O2/4 days), 5x10(-6)M sodium stearate: albumin in 6:1 ratio/30 min, KCN (1x10(-3)M/1 hr), 2 deoxy-glucose (3x10(-2)M/12 hr), acidosis (pH 6.9/30 min) and combinations. KCN plus 2-DG labilized the organelles in both cell types. Sensitivity to injury was in the order mitochondria greater than lysosomes and muscle cells greater than endothelioid cells."}
{"id": "PMID:242049", "title": "Stimulus interaction in the responses of carotid body chemoreceptor single afferent fibers.", "content": "The characteristics of steady-state responses of single afferent fibers of carotid chemoreceptors to independent changes in arterial Po2, and Pco2 were investigated in cats. The arterial blood pressure was maintained within the normal limits (115-130 torr). Single chemoreceptor afferent fibers responded to changes both in arterial Po2 and Pco2. The relationship between the activity of chemoreceptors and changes in arterial Pco2 was linear at a constant arterial Po2. The two stimuli showed multiplicative interaction. The activity approached zero (threshold) as arterial Pco2 was decreased at a constant arterial Po2; a decrease in arterial Po2 decreased the arterial Pco2 threshold. These response characteristics of a single fiber suggest that the sensory receptor may be activated through a single mechanism by the two stimuli. The data fit into an idea that the mechanism may involve a conformational change in the membrane-bound polymeric chromophore group which reacts with O2 reversibly and shows a Bohr-shift.", "contents": "Stimulus interaction in the responses of carotid body chemoreceptor single afferent fibers. The characteristics of steady-state responses of single afferent fibers of carotid chemoreceptors to independent changes in arterial Po2, and Pco2 were investigated in cats. The arterial blood pressure was maintained within the normal limits (115-130 torr). Single chemoreceptor afferent fibers responded to changes both in arterial Po2 and Pco2. The relationship between the activity of chemoreceptors and changes in arterial Pco2 was linear at a constant arterial Po2. The two stimuli showed multiplicative interaction. The activity approached zero (threshold) as arterial Pco2 was decreased at a constant arterial Po2; a decrease in arterial Po2 decreased the arterial Pco2 threshold. These response characteristics of a single fiber suggest that the sensory receptor may be activated through a single mechanism by the two stimuli. The data fit into an idea that the mechanism may involve a conformational change in the membrane-bound polymeric chromophore group which reacts with O2 reversibly and shows a Bohr-shift."}
{"id": "PMID:242050", "title": "Relationship between carotid chemoreceptor activity and ventilation in the cat.", "content": "The steady-state stimulus-response relations between arterial P02 and PCO2 and the mean activity of carotid chemoreceptors (single and multi-fiber) and ventilation were simultaneously recorded in 48 anesthetized cats. The carotid chemoreceptor activity varied linearly with the increase of arterial PCO2, below and above the normal value, at any given level of arterial P02. A decrease in arterial P02 increased the activity of the carotid chemoreceptors and increased its sensitivity to changes in arterial PCO2, showing multiplicative stimulus interaction. The authors also found that the response in ventilation during hypoxia to changes in arterial PCO2 below the normal value was smaller than that to changes above it, unlike the response of carotid chemoreceptors. This arterial PCO2 quasi-threshold for ventilation was, therefore, not due to a corresponding threshold for the activity of the carotid chemoreceptors but to a central mechanism. Above the central PaCO2 threshold, the ventilatory response to changes in PaCO2 and Pa02 resembled that of chemoreceptors but the ventilation dependent on hypoxia was greater than that could be directly accounted for by the activity of peripheral chemorecepors. A multiplicative interaction between the activity of peripheral chemoreceptors and central CO2 excitation appears to play a role in the regulation of ventilation.", "contents": "Relationship between carotid chemoreceptor activity and ventilation in the cat. The steady-state stimulus-response relations between arterial P02 and PCO2 and the mean activity of carotid chemoreceptors (single and multi-fiber) and ventilation were simultaneously recorded in 48 anesthetized cats. The carotid chemoreceptor activity varied linearly with the increase of arterial PCO2, below and above the normal value, at any given level of arterial P02. A decrease in arterial P02 increased the activity of the carotid chemoreceptors and increased its sensitivity to changes in arterial PCO2, showing multiplicative stimulus interaction. The authors also found that the response in ventilation during hypoxia to changes in arterial PCO2 below the normal value was smaller than that to changes above it, unlike the response of carotid chemoreceptors. This arterial PCO2 quasi-threshold for ventilation was, therefore, not due to a corresponding threshold for the activity of the carotid chemoreceptors but to a central mechanism. Above the central PaCO2 threshold, the ventilatory response to changes in PaCO2 and Pa02 resembled that of chemoreceptors but the ventilation dependent on hypoxia was greater than that could be directly accounted for by the activity of peripheral chemorecepors. A multiplicative interaction between the activity of peripheral chemoreceptors and central CO2 excitation appears to play a role in the regulation of ventilation."}
{"id": "PMID:242051", "title": "Oxygen consumption and conservation during apnea in the anesthetized dog.", "content": "Apnea was initiated by clamping off the tracheal tube in 6 anesthetized dogs. Bradycardia, reduction in cardiac output and peripheral vasoconstriction developed gradually throughout the entire apneic period. O2 consumption during apnea was measured by monitoring the rate of O2  removal from the lung (VLO2), from the arterial blood (Va02), and from the venous blood (VV02). Total 02 consumption (VT02) was calculated by summing (VL02--Va02), VaQ2 and VV02-VL02, estimated by the product of arteriovenous O2 content difference and cardiac output, decreased continuously during apnea. At the end of 80 sec the rate of O2 removal from the lung was one-fourth of the pre-apneic rate, 5.29 +/- 0.51 ml-min-1kg-1. Oxygen disappearance form the blood was estimated by measuring arterial and venous O2 content at 20-sec intervals and by assuming a constant blood volume throughout the apneic period of 86 ml/kg, 25% of which is in the arterial tree and 75% of which is in the venous compartment. During the last 20 sec of an 80-sec apnea, VV02 represented 69% of VT02. The result indicated that VT02 during apnea was not significantly different from that of pre-apneic values. It is concluded from the present study that an oxygen conservation mechanism if existent, was not operative during an 80-sec apnea in the anesthetized dog.", "contents": "Oxygen consumption and conservation during apnea in the anesthetized dog. Apnea was initiated by clamping off the tracheal tube in 6 anesthetized dogs. Bradycardia, reduction in cardiac output and peripheral vasoconstriction developed gradually throughout the entire apneic period. O2 consumption during apnea was measured by monitoring the rate of O2  removal from the lung (VLO2), from the arterial blood (Va02), and from the venous blood (VV02). Total 02 consumption (VT02) was calculated by summing (VL02--Va02), VaQ2 and VV02-VL02, estimated by the product of arteriovenous O2 content difference and cardiac output, decreased continuously during apnea. At the end of 80 sec the rate of O2 removal from the lung was one-fourth of the pre-apneic rate, 5.29 +/- 0.51 ml-min-1kg-1. Oxygen disappearance form the blood was estimated by measuring arterial and venous O2 content at 20-sec intervals and by assuming a constant blood volume throughout the apneic period of 86 ml/kg, 25% of which is in the arterial tree and 75% of which is in the venous compartment. During the last 20 sec of an 80-sec apnea, VV02 represented 69% of VT02. The result indicated that VT02 during apnea was not significantly different from that of pre-apneic values. It is concluded from the present study that an oxygen conservation mechanism if existent, was not operative during an 80-sec apnea in the anesthetized dog."}
{"id": "PMID:242052", "title": "Factors causing and reversing vasoconstriction in unventilated lung.", "content": "Vasoconstriction occuring a unventilated or hypoxic lung was studied in dogs and cats to elucidate mechanisms which both cause and reverse it. Lungs were perfused in vivo at constant pressure or constant blood flow; alternatively blood flow and pressure were measured with minimal operative interference. Stimulus-response curves of lung vessels to hypoxia showed a large response within the physiological range of P02 values. Vasoconstriction in unventilated lung caused by bronchial occlusion sometimes matched that caused by an equal degree of ventilation hypoxia but was sometimes greater. Responses to both stimuli varied widely between animals and in one animal at different times. This could be due to variable availability of a transmitter or variable presence of vasodilator substances. Both histamine and beta-adrenoreceptor stimulants caused pulmonary vasodilatation in unventilated lung. Histamine caused pulmonary vasoconstriction and vasodilatation in different circumstances which could be blocked respectively by H1 and H2 antihistamine drugs. Potent alpha- and beta-adrenoreceptor action on pulmonary vessels was demonstrated in both species. Alpha-adrenoreceptor blocking drugs caused dilatation and beta-adrenoreceptor blocking drugs caused vasoconstriction. The possible role of histamine and catecholamines in causing or reversing hypoxic vasoconstriction or in maintaining pulmonary vascular tone is discussed.", "contents": "Factors causing and reversing vasoconstriction in unventilated lung. Vasoconstriction occuring a unventilated or hypoxic lung was studied in dogs and cats to elucidate mechanisms which both cause and reverse it. Lungs were perfused in vivo at constant pressure or constant blood flow; alternatively blood flow and pressure were measured with minimal operative interference. Stimulus-response curves of lung vessels to hypoxia showed a large response within the physiological range of P02 values. Vasoconstriction in unventilated lung caused by bronchial occlusion sometimes matched that caused by an equal degree of ventilation hypoxia but was sometimes greater. Responses to both stimuli varied widely between animals and in one animal at different times. This could be due to variable availability of a transmitter or variable presence of vasodilator substances. Both histamine and beta-adrenoreceptor stimulants caused pulmonary vasodilatation in unventilated lung. Histamine caused pulmonary vasoconstriction and vasodilatation in different circumstances which could be blocked respectively by H1 and H2 antihistamine drugs. Potent alpha- and beta-adrenoreceptor action on pulmonary vessels was demonstrated in both species. Alpha-adrenoreceptor blocking drugs caused dilatation and beta-adrenoreceptor blocking drugs caused vasoconstriction. The possible role of histamine and catecholamines in causing or reversing hypoxic vasoconstriction or in maintaining pulmonary vascular tone is discussed."}
{"id": "PMID:242053", "title": "Oxygen uptake and blood respiratory properties of the caecilian Boulengerula taitanus.", "content": "In contrast to amphibians belonging to the orders Urodela and Anura, virtually no data exist on the respiratory physiology of the more primitive Apoda. This study concerns oxygen uptake and hemoglobin function in the caecilan Boulengerula taitanus, an apodan with fossorial habits. The oxygen uptake rate resembles that of other amphibians of similar size. The blood was high O2 capacity (14 vol%) and the erythrocytes are smaller, and the red cell count is greater than in other amphibians. The oxygen affinity of whole blood is high compared to other amphibians (P50 = 28 mm Hg at 25 degrees C and pH 7.6). The oxygen equilibrium curve is sigmoid (n = 1.79) and the Bohr factor is small (deltalog P50/deltapH = - 0.21). In 'stripped' hemoglobin solutions oxygen affinity increases strongly (P50 = 3.3 mm Hg at 25 degrees C and pH 7.6) and the temperature sensitivity is high (apparent deltaH=-19.4 kcal/mole), but the ATP and pH influences are too low to account for the difference in P50 compared to whole blood. The high oxygen capacity and oxygen affinity and the low Bohr factor may have adaptive significance to this fossorial amphibian.", "contents": "Oxygen uptake and blood respiratory properties of the caecilian Boulengerula taitanus. In contrast to amphibians belonging to the orders Urodela and Anura, virtually no data exist on the respiratory physiology of the more primitive Apoda. This study concerns oxygen uptake and hemoglobin function in the caecilan Boulengerula taitanus, an apodan with fossorial habits. The oxygen uptake rate resembles that of other amphibians of similar size. The blood was high O2 capacity (14 vol%) and the erythrocytes are smaller, and the red cell count is greater than in other amphibians. The oxygen affinity of whole blood is high compared to other amphibians (P50 = 28 mm Hg at 25 degrees C and pH 7.6). The oxygen equilibrium curve is sigmoid (n = 1.79) and the Bohr factor is small (deltalog P50/deltapH = - 0.21). In 'stripped' hemoglobin solutions oxygen affinity increases strongly (P50 = 3.3 mm Hg at 25 degrees C and pH 7.6) and the temperature sensitivity is high (apparent deltaH=-19.4 kcal/mole), but the ATP and pH influences are too low to account for the difference in P50 compared to whole blood. The high oxygen capacity and oxygen affinity and the low Bohr factor may have adaptive significance to this fossorial amphibian."}
{"id": "PMID:242072", "title": "Gastro-oesophageal acid reflux and sphincter pressure in normal human subjects.", "content": "Twelve-hour continuous recording of pH at the distal end of the oesophagus and manometric study of the basal gastro-oesophageal sphincter pressure were carried out in 26 normal human subjects. Eighteen of the 26 had 1-33 reflux episodes. The duration of each episode was shorter than 15 min in 16 of these 18 subjects. One single reflux episode lasting 15-30 min occurred in two, and one lasting 30-45 min was recorded in one. The total duration of low pH is expressed in percentages of the total time of recording and is dependent on the criteria used for low pH. On automatic analysis of the course of investigation, pH below 2.3 was found in five, pH below 3 in 17, and pH below 4 and 5, in 18 of the 26 subjects. Basal gastro-oesophageal sphincter pressure flutuated between 8 and 24 mmHg. The results of the study would suggest that in healthy, asymptomatic individuals the gastro-oesophageal barrier against reflux may be periodically incompetent. If contact between acid gastric contents and the oesophageal mucosa is a factor provoking the symptom heartburn, low oesophageal pH need not necessarily give rise to symptoms, i.e. the sensibility to low pH is either individual, or patients with symptoms have considerably more frequent and longer lasting episodes of reflux with low oesophageal pH than have normal subjects.", "contents": "Gastro-oesophageal acid reflux and sphincter pressure in normal human subjects. Twelve-hour continuous recording of pH at the distal end of the oesophagus and manometric study of the basal gastro-oesophageal sphincter pressure were carried out in 26 normal human subjects. Eighteen of the 26 had 1-33 reflux episodes. The duration of each episode was shorter than 15 min in 16 of these 18 subjects. One single reflux episode lasting 15-30 min occurred in two, and one lasting 30-45 min was recorded in one. The total duration of low pH is expressed in percentages of the total time of recording and is dependent on the criteria used for low pH. On automatic analysis of the course of investigation, pH below 2.3 was found in five, pH below 3 in 17, and pH below 4 and 5, in 18 of the 26 subjects. Basal gastro-oesophageal sphincter pressure flutuated between 8 and 24 mmHg. The results of the study would suggest that in healthy, asymptomatic individuals the gastro-oesophageal barrier against reflux may be periodically incompetent. If contact between acid gastric contents and the oesophageal mucosa is a factor provoking the symptom heartburn, low oesophageal pH need not necessarily give rise to symptoms, i.e. the sensibility to low pH is either individual, or patients with symptoms have considerably more frequent and longer lasting episodes of reflux with low oesophageal pH than have normal subjects."}
{"id": "PMID:242073", "title": "Elevation of serum gamma-glutamyl transpeptidase in end-stage chronic renal failure.", "content": "The serum gamma-glutamyl transpeptidase (GGT) was measured on 32 randomly selected patients about to commence or already on chronic haemodialysis. Raised values were found in 12 patients (37%). None of these patients had received drugs known to affect hepatic microsomes and all had normal liver function tests. The possible significance of this surprising finding is discussed.", "contents": "Elevation of serum gamma-glutamyl transpeptidase in end-stage chronic renal failure. The serum gamma-glutamyl transpeptidase (GGT) was measured on 32 randomly selected patients about to commence or already on chronic haemodialysis. Raised values were found in 12 patients (37%). None of these patients had received drugs known to affect hepatic microsomes and all had normal liver function tests. The possible significance of this surprising finding is discussed."}
{"id": "PMID:242075", "title": "Substance p: localization in the central nervous system and in some primary sensory neurons.", "content": "Antibodies to substance P with a high titer have been produced and used in immunohistochemical studies on the peripheral and central nervous system of the rat and the cat. Evidence was obtained for the localization of substance P in a certain population of primary sensory neurons, probably small nerve cells with unmyelinated processes. Substance P or a peptide similar to it was also observed in cell bodies in the medial habenula and in probable nerve terminals in many brain areas. The results give morphological support for a transmitter (or modulator) role of substance P in the nervous system.", "contents": "Substance p: localization in the central nervous system and in some primary sensory neurons. Antibodies to substance P with a high titer have been produced and used in immunohistochemical studies on the peripheral and central nervous system of the rat and the cat. Evidence was obtained for the localization of substance P in a certain population of primary sensory neurons, probably small nerve cells with unmyelinated processes. Substance P or a peptide similar to it was also observed in cell bodies in the medial habenula and in probable nerve terminals in many brain areas. The results give morphological support for a transmitter (or modulator) role of substance P in the nervous system."}
{"id": "PMID:242076", "title": "Reproductive tract lesions in male mice exposed prenatally to diethylstilbestrol.", "content": "Sixty percent of the male offspring from pregnant mice treated with diethylstilbestrol during gestation were sterile. The affected animals had gonadal changes which included intra-abdominal or fibrotic testes, or both. Additionally, nodular masses in the ampullary region of the reproductive tract were observed in 6 of 24 animals; one of these appeared to be preneoplastic.", "contents": "Reproductive tract lesions in male mice exposed prenatally to diethylstilbestrol. Sixty percent of the male offspring from pregnant mice treated with diethylstilbestrol during gestation were sterile. The affected animals had gonadal changes which included intra-abdominal or fibrotic testes, or both. Additionally, nodular masses in the ampullary region of the reproductive tract were observed in 6 of 24 animals; one of these appeared to be preneoplastic."}
{"id": "PMID:242077", "title": "Lysinoalanine: presence in foods and food ingredients.", "content": "Lysinoalanine, N6-(DL-2-amino-2-carboxyethyl)-L-lysine, an unusual amino acid implicated as a renal toxic factor in rats, has been found in proteins of home-cooked and commercial foods and ingredients. Although it has been reported to occur in both edible and nonfood proteins only after alkali treatment, it has now been identified in food proteins that had not been subjected to alkali. Lysinoalanine is generated in a variety of proteins when heated under nonalkaline conditions.", "contents": "Lysinoalanine: presence in foods and food ingredients. Lysinoalanine, N6-(DL-2-amino-2-carboxyethyl)-L-lysine, an unusual amino acid implicated as a renal toxic factor in rats, has been found in proteins of home-cooked and commercial foods and ingredients. Although it has been reported to occur in both edible and nonfood proteins only after alkali treatment, it has now been identified in food proteins that had not been subjected to alkali. Lysinoalanine is generated in a variety of proteins when heated under nonalkaline conditions."}
{"id": "PMID:242081", "title": "Some factors affecting bone formation: a review.", "content": "Two separate methods exist at present to induce new bone formation. One utilises the implantation of specific materials, which may be of biological or non-biological origin. The other is based on the finding that bony tissue responds to very small electrical currents by stimulating osteogenesis at the negative electrode. This article discusses these methods in detail.", "contents": "Some factors affecting bone formation: a review. Two separate methods exist at present to induce new bone formation. One utilises the implantation of specific materials, which may be of biological or non-biological origin. The other is based on the finding that bony tissue responds to very small electrical currents by stimulating osteogenesis at the negative electrode. This article discusses these methods in detail."}
{"id": "PMID:242082", "title": "A modified reduced transport fluid for the preservation of Neisseria gonorrhoeae during transport.", "content": "Reduced transport fluid (RTF) was modified by altering its pH and by the addition of a yeast dialysate. This reduced transport yeast-containing fluid (RTYF) was shown to be superior to RTF in maintaining viability of Neisseria gonorrhoeae in cultures and in clinical material.", "contents": "A modified reduced transport fluid for the preservation of Neisseria gonorrhoeae during transport. Reduced transport fluid (RTF) was modified by altering its pH and by the addition of a yeast dialysate. This reduced transport yeast-containing fluid (RTYF) was shown to be superior to RTF in maintaining viability of Neisseria gonorrhoeae in cultures and in clinical material."}
{"id": "PMID:242083", "title": "Benzodiazepines in psychiatry.", "content": "There are many difficulties in evaluating the efficacy of anxiolytic drugs, but their widespread and increasing clinical use confirms their effectiveness. The benzodiazepines, the most popular agents, offer certain advantages over the others. This article summarises the chemical properties and clinical effects of the benzodiazepines, and propose guidelines for the rational use of these agents in clinical practice.", "contents": "Benzodiazepines in psychiatry. There are many difficulties in evaluating the efficacy of anxiolytic drugs, but their widespread and increasing clinical use confirms their effectiveness. The benzodiazepines, the most popular agents, offer certain advantages over the others. This article summarises the chemical properties and clinical effects of the benzodiazepines, and propose guidelines for the rational use of these agents in clinical practice."}
{"id": "PMID:242084", "title": "Antimicrobial activity of human peritoneal fluid.", "content": "Cell free peritoneal fluids from 23 normal women had antimicrobial activity which was directed against gram-positive and gram-negative bacteria and also against yeasts. The activity was bacteriostatic or bactericidal and seemed to be due to the presence of a variety of factors which varied in their heat stability and dependence on complement. Lysozyme was present in the fluids but was not responsible for all the antimicrobial activity.", "contents": "Antimicrobial activity of human peritoneal fluid. Cell free peritoneal fluids from 23 normal women had antimicrobial activity which was directed against gram-positive and gram-negative bacteria and also against yeasts. The activity was bacteriostatic or bactericidal and seemed to be due to the presence of a variety of factors which varied in their heat stability and dependence on complement. Lysozyme was present in the fluids but was not responsible for all the antimicrobial activity."}
{"id": "PMID:242085", "title": "Orthotopic liver transplantation after preservation without perfusion for up to six hours: A controlled trial evaluating different preservation fluids in dogs and pigs.", "content": "The important extension of the ischemic period recently described with a simple hypothermic liver preservation method is attributed to the use of specific preservation fluids. However, there is no consensus about the optimal preservation fluid. In order to investigate the effect of the composition of the preservation fluid on the immediately postoperative transplant function and on subsequent long-term survival, orthotopic liver transplantations were performed in 13 dogs and 12 pigs. To reduce immunologic interference in postoperative transplant evaluation, donor and recipient pairs always were litter mates, the dogs being identical according to lymphocyte typing. The ischemic periods were 1, 3, and 6 hours. Four different preservation fluids were used with marked differences in ionic composition (extracellular vs. intracellular), pH, and osmolarity. Within each ischemic period group the sequence of experiments was randomized with respect to the different preservation fluids. Twenty-four animals survived the transplantation procedure. No differences were found between the preservation fluid groups. Postoperative function of all livers preserved for 6 hours was comparable to those with 1 hour ischemia. Three dogs and four pigs (six of seven with livers preserved for 3 to 6 hours) are still alive more than 1 year after transplantation. So consistently excellent liver function leading to long-term survival in 36 percent of cases can be obtained after liver transplantation with preservation up to 6 hours; for this result the composition of the preservation fluid is of minor importance.", "contents": "Orthotopic liver transplantation after preservation without perfusion for up to six hours: A controlled trial evaluating different preservation fluids in dogs and pigs. The important extension of the ischemic period recently described with a simple hypothermic liver preservation method is attributed to the use of specific preservation fluids. However, there is no consensus about the optimal preservation fluid. In order to investigate the effect of the composition of the preservation fluid on the immediately postoperative transplant function and on subsequent long-term survival, orthotopic liver transplantations were performed in 13 dogs and 12 pigs. To reduce immunologic interference in postoperative transplant evaluation, donor and recipient pairs always were litter mates, the dogs being identical according to lymphocyte typing. The ischemic periods were 1, 3, and 6 hours. Four different preservation fluids were used with marked differences in ionic composition (extracellular vs. intracellular), pH, and osmolarity. Within each ischemic period group the sequence of experiments was randomized with respect to the different preservation fluids. Twenty-four animals survived the transplantation procedure. No differences were found between the preservation fluid groups. Postoperative function of all livers preserved for 6 hours was comparable to those with 1 hour ischemia. Three dogs and four pigs (six of seven with livers preserved for 3 to 6 hours) are still alive more than 1 year after transplantation. So consistently excellent liver function leading to long-term survival in 36 percent of cases can be obtained after liver transplantation with preservation up to 6 hours; for this result the composition of the preservation fluid is of minor importance."}
{"id": "PMID:242086", "title": "Sympathectomy revisited: Dodo or phoenix?", "content": "Personal experience with temporary or permanent interruption of adrenergic impulses to brain, heart, kidney, pancreas, and the extemities is reviewed and certain concepts which were formulated long ago are re-emphasized. First, adrenergic blockade unmasks the cholinergic activity of the autonomic nervous system. This is apparent particularly when cardiac, renal, or pancreatic functions are studied under stress. Second, in the immediate treatment of cerebral, cardiac, or digital ischemia, the potentially reversible halo of edema around the irreversible necrosis is rapidly influenced by ganglionic blockade. And third, attention is called to the effect of adrenergic stimulation on sensory nerve endings which develop a higher threshold for pain when sympathetic fibers are interrupted. Although potent drugs inhibiting alpha and beta receptors or the release of catecholamines are widely in use, the obvious advantages of regional vs. systemic interruption of adrenergic impulses is pointed out. When the latter approach is pursued aggressively, the side effects are those of a total sympathectomy.", "contents": "Sympathectomy revisited: Dodo or phoenix? Personal experience with temporary or permanent interruption of adrenergic impulses to brain, heart, kidney, pancreas, and the extemities is reviewed and certain concepts which were formulated long ago are re-emphasized. First, adrenergic blockade unmasks the cholinergic activity of the autonomic nervous system. This is apparent particularly when cardiac, renal, or pancreatic functions are studied under stress. Second, in the immediate treatment of cerebral, cardiac, or digital ischemia, the potentially reversible halo of edema around the irreversible necrosis is rapidly influenced by ganglionic blockade. And third, attention is called to the effect of adrenergic stimulation on sensory nerve endings which develop a higher threshold for pain when sympathetic fibers are interrupted. Although potent drugs inhibiting alpha and beta receptors or the release of catecholamines are widely in use, the obvious advantages of regional vs. systemic interruption of adrenergic impulses is pointed out. When the latter approach is pursued aggressively, the side effects are those of a total sympathectomy."}
{"id": "PMID:242089", "title": "Purification and some properties of urokinase.", "content": "A method for efficient extraction of urokinase from human urine was established by using polyacrylonitrile synthetic fiber as an adsorbent. By a combination of this method and known methods for purification of proteins, such as gel filtration and ion-exchange chromatography, urokinase with a specific activity of 224,000 International Units per mg of protein was obtained. This sample showed homogeneity by ultracentrifugation, moving-boundary electrophoresis at pH 4.8 and 9.0 and polyacrylamide gel disc electrophoresis at pH 4.0, but was separated into five active fractions by isoelectric focusing and polyacrylamide gel disc electrophoresis at pH 9.4. This sample showed a single precipitin line in double radial immunodiffusion and immunoelectrophoresis using rabbit anti-urokinase serum. This precipitin line fused with that of the International Standard preparation of urokinase and its immunological identity was established. The molecular weight of this sample was 33,000, agreeing with that of the International Standard preparation. Its optimal pH as a plasminogen activator was approximately 8.8.", "contents": "Purification and some properties of urokinase. A method for efficient extraction of urokinase from human urine was established by using polyacrylonitrile synthetic fiber as an adsorbent. By a combination of this method and known methods for purification of proteins, such as gel filtration and ion-exchange chromatography, urokinase with a specific activity of 224,000 International Units per mg of protein was obtained. This sample showed homogeneity by ultracentrifugation, moving-boundary electrophoresis at pH 4.8 and 9.0 and polyacrylamide gel disc electrophoresis at pH 4.0, but was separated into five active fractions by isoelectric focusing and polyacrylamide gel disc electrophoresis at pH 9.4. This sample showed a single precipitin line in double radial immunodiffusion and immunoelectrophoresis using rabbit anti-urokinase serum. This precipitin line fused with that of the International Standard preparation of urokinase and its immunological identity was established. The molecular weight of this sample was 33,000, agreeing with that of the International Standard preparation. Its optimal pH as a plasminogen activator was approximately 8.8."}
{"id": "PMID:242090", "title": "The effects of biguanides on thrombokinase, thrombin and trypsin.", "content": "A purified preparation of bovine thrombokinase (activated Factor X) loses the ability to hydrolyze TAME (p-toluenesulfonyl-L-arginine methyl ester) when it is incubated at 37 degrees in 0.25 M Tris. HCl buffer, pH 7.4 with lauroxypropyl biguanide, N1, N5-dimethyl, N1-lauroxypropyl biguanide, N1-p-chlorophenethyl, N5-phenethyl biguanide, or N1-methyl, N1-p-chlorobenzyl, N5-o,p-dichlorobenzyl biguanide. Activity is lost much more slowly when 0.15 M NaCl is also present. Lauroxypropyl biguanide is the most potent of the compounds tested, 0.22 mM causing thrombokinase to lose almost all of its activity in about 30 minutes at 37 degrees in pH 7.4 buffered saline. Topical bovine thrombin also loses activity when incubated with either of the lauroxypropyl biguanides but not with the diphenethyl or the dibenzyl compound. Instead, the latter biguanides accelerate thrombin's hydrolysis of TAME. The percent acceleration is not affected or only slightly decreased by the presence of 0.15 M NaCl or KCl, and it is also unaffected by incubating the enzyme with the compounds in buffered saline for 4 to 120 minutes. Purified bovine trypsin is stabilized by both lauroxypropyl and the diphenethyl biguanide when incubated at 37 degrees in pH 7.4 buffered saline for the 60 minute test period but neither compounds has any effect on its rate of hydrolysis of TAME. It is postulated that the enzymes first react rapidly and reversibly with all of the test biguanides and, depending upon the enzyme and the substrate, the rate of hydrolysis of the substrate is unaffected, accelerated or inhibited. The lauroxypropyl biguanides also undergo a second, slower reaction with both thrombokinase and thrombin that produces loss of enzymatic activity. The dibenzyl and diphenethyl biguanides also undergo this second slow reaction with thrombokinase but not with thrombin, and none of the biguanides undergo this second reaction with trypsin.", "contents": "The effects of biguanides on thrombokinase, thrombin and trypsin. A purified preparation of bovine thrombokinase (activated Factor X) loses the ability to hydrolyze TAME (p-toluenesulfonyl-L-arginine methyl ester) when it is incubated at 37 degrees in 0.25 M Tris. HCl buffer, pH 7.4 with lauroxypropyl biguanide, N1, N5-dimethyl, N1-lauroxypropyl biguanide, N1-p-chlorophenethyl, N5-phenethyl biguanide, or N1-methyl, N1-p-chlorobenzyl, N5-o,p-dichlorobenzyl biguanide. Activity is lost much more slowly when 0.15 M NaCl is also present. Lauroxypropyl biguanide is the most potent of the compounds tested, 0.22 mM causing thrombokinase to lose almost all of its activity in about 30 minutes at 37 degrees in pH 7.4 buffered saline. Topical bovine thrombin also loses activity when incubated with either of the lauroxypropyl biguanides but not with the diphenethyl or the dibenzyl compound. Instead, the latter biguanides accelerate thrombin's hydrolysis of TAME. The percent acceleration is not affected or only slightly decreased by the presence of 0.15 M NaCl or KCl, and it is also unaffected by incubating the enzyme with the compounds in buffered saline for 4 to 120 minutes. Purified bovine trypsin is stabilized by both lauroxypropyl and the diphenethyl biguanide when incubated at 37 degrees in pH 7.4 buffered saline for the 60 minute test period but neither compounds has any effect on its rate of hydrolysis of TAME. It is postulated that the enzymes first react rapidly and reversibly with all of the test biguanides and, depending upon the enzyme and the substrate, the rate of hydrolysis of the substrate is unaffected, accelerated or inhibited. The lauroxypropyl biguanides also undergo a second, slower reaction with both thrombokinase and thrombin that produces loss of enzymatic activity. The dibenzyl and diphenethyl biguanides also undergo this second slow reaction with thrombokinase but not with thrombin, and none of the biguanides undergo this second reaction with trypsin."}
{"id": "PMID:242092", "title": "The influence of ascorbic acid on platelet structure and function.", "content": "To determine the effect on platelet behavior of transient exposure of platelets to ascorbic acid, studies of platelet function and ultrastructure were done before exposure to ascorbic acid at pH 6.5, during exposure to pH 6.5, and after restoration of pH to pre-acidification levels. The effect of ascorbic acid (A.A.) was compared to that of HCl and citric acid (C.A.). ADP- and collagen-induced aggregation of normal platelets were significantly impaired by both A.A. and C.A. but were less affected by HCl. The release of 14C-serotonin was significantly reduced by each agent. The ultrastructure of normal platelets brought to pH 6.5 by A.A. was normal. After neutralization, there was marked dilatation of the open channel system and loss of the disc shape. When platelets were brought to pH 6.5 by A.A., then neutralized, the aggregates which formed after stimulation by ADP or collagen were smaller than normal, the platelets were less closely approximated, and degranulation was less complete. The data show that exposure of platelets to ascorbic acid for short intervals impairs their function when measured after restoration of pH to levels compatible with maximal responses. Platelet survival studies using autologous platelets labelled with 51Cr in the presence or absence of ascorbic acid showed that the recovery of normal platelets was unaffected by ascorbic acid, whereas recovery of platelets from patients with idiopathic thrombocytopenic purpura, idiopathic thrombocythemia, and alcohol-related thrombocytopenia was markedly reduced. The injury resulting from the use of ascorbic acid in preparing platelets for studies of platelet survival in patients with disorders affecting platelets may impair the recovery of the cells, resulting in artifactual changes in the survival studies.", "contents": "The influence of ascorbic acid on platelet structure and function. To determine the effect on platelet behavior of transient exposure of platelets to ascorbic acid, studies of platelet function and ultrastructure were done before exposure to ascorbic acid at pH 6.5, during exposure to pH 6.5, and after restoration of pH to pre-acidification levels. The effect of ascorbic acid (A.A.) was compared to that of HCl and citric acid (C.A.). ADP- and collagen-induced aggregation of normal platelets were significantly impaired by both A.A. and C.A. but were less affected by HCl. The release of 14C-serotonin was significantly reduced by each agent. The ultrastructure of normal platelets brought to pH 6.5 by A.A. was normal. After neutralization, there was marked dilatation of the open channel system and loss of the disc shape. When platelets were brought to pH 6.5 by A.A., then neutralized, the aggregates which formed after stimulation by ADP or collagen were smaller than normal, the platelets were less closely approximated, and degranulation was less complete. The data show that exposure of platelets to ascorbic acid for short intervals impairs their function when measured after restoration of pH to levels compatible with maximal responses. Platelet survival studies using autologous platelets labelled with 51Cr in the presence or absence of ascorbic acid showed that the recovery of normal platelets was unaffected by ascorbic acid, whereas recovery of platelets from patients with idiopathic thrombocytopenic purpura, idiopathic thrombocythemia, and alcohol-related thrombocytopenia was markedly reduced. The injury resulting from the use of ascorbic acid in preparing platelets for studies of platelet survival in patients with disorders affecting platelets may impair the recovery of the cells, resulting in artifactual changes in the survival studies."}
{"id": "PMID:242093", "title": "Hyperaggregability of platelets in thromboembolic disorders.", "content": "Platelet aggregability was measured using platelet rich plasma (PRP) collected from 197 clinical cases including 52 healthy volunteers. In 31 patients of acute stage of thrombosis (within 2 weeks from the onset), a significant enhancement of platelet aggregation measured 5 min after an addition of 3 and 10 muM ADP or 0.1 and 1 mug/ml of adrenaline to PRP (p less than 0.05, compared to the healthy group). Also a significant enhancement of secondary aggregation induced by adrenaline was observed (p less than 0.05). The enhancement was especially marked in the response induced by adrenaline. Such an enhancement was not observed in patients in the recovery stage of thrombosis, hypertension, angina pectoris and other miscellaneous diseases. There was no difference in the parameters related to the velocity of aggregation or intensity of primary aggregation between the diseased and the healthy group. In response induced by collagen (bovine achilles tendon, 0.3 and 1 mg/ml) any difference in the aggregation curve was not observed between the diseased and the healthy group. Such findings suggest a presence of an enhancement of ADP-release mechanism of platelets in acute thrombosis. Aslo a significance of adrenaline-induced platelet aggregation was proposed to detect platelet functions for analysis of mechanism of thromboembolic disorders.", "contents": "Hyperaggregability of platelets in thromboembolic disorders. Platelet aggregability was measured using platelet rich plasma (PRP) collected from 197 clinical cases including 52 healthy volunteers. In 31 patients of acute stage of thrombosis (within 2 weeks from the onset), a significant enhancement of platelet aggregation measured 5 min after an addition of 3 and 10 muM ADP or 0.1 and 1 mug/ml of adrenaline to PRP (p less than 0.05, compared to the healthy group). Also a significant enhancement of secondary aggregation induced by adrenaline was observed (p less than 0.05). The enhancement was especially marked in the response induced by adrenaline. Such an enhancement was not observed in patients in the recovery stage of thrombosis, hypertension, angina pectoris and other miscellaneous diseases. There was no difference in the parameters related to the velocity of aggregation or intensity of primary aggregation between the diseased and the healthy group. In response induced by collagen (bovine achilles tendon, 0.3 and 1 mg/ml) any difference in the aggregation curve was not observed between the diseased and the healthy group. Such findings suggest a presence of an enhancement of ADP-release mechanism of platelets in acute thrombosis. Aslo a significance of adrenaline-induced platelet aggregation was proposed to detect platelet functions for analysis of mechanism of thromboembolic disorders."}
{"id": "PMID:242097", "title": "Changes in plasma levels of LH, FSH and testosterone following the administration of synthetic luteinizing hormone-releasing hormone to cryptorchid patients.", "content": "The levels of LH, FSH and testosterone of three adult groups consisting of normal subjects, unilateral and bilateral cryptorcids were compared before and after LH-RH loading. It was found that both groups of cryptorchid had comparatively high plasma base line levels for both LH and FSH, particularly high in the bilateral group; and both groups responded to LH-RH loading. This indicates that their hypothalamo-hypophyseal systems were probably functioning normally. The plasma base line levels of testosterone were higher in unilateral cryptorchids than in the control group, and lowest in the bilateral cryptorchid group. But the reaction of testosterone levels to LH-RH loading was generally poor in both groups of cryptorchids, suggesting that, in cryptorchid cases, unilateral and bilateral, the capacity of the testicle to secrete testosterone is generally depressed, freeing central suppression. This probably accounts for the high values of plasma lh and FSH observed in such patients.", "contents": "Changes in plasma levels of LH, FSH and testosterone following the administration of synthetic luteinizing hormone-releasing hormone to cryptorchid patients. The levels of LH, FSH and testosterone of three adult groups consisting of normal subjects, unilateral and bilateral cryptorcids were compared before and after LH-RH loading. It was found that both groups of cryptorchid had comparatively high plasma base line levels for both LH and FSH, particularly high in the bilateral group; and both groups responded to LH-RH loading. This indicates that their hypothalamo-hypophyseal systems were probably functioning normally. The plasma base line levels of testosterone were higher in unilateral cryptorchids than in the control group, and lowest in the bilateral cryptorchid group. But the reaction of testosterone levels to LH-RH loading was generally poor in both groups of cryptorchids, suggesting that, in cryptorchid cases, unilateral and bilateral, the capacity of the testicle to secrete testosterone is generally depressed, freeing central suppression. This probably accounts for the high values of plasma lh and FSH observed in such patients."}
{"id": "PMID:242098", "title": "The depressor effect of dopamine on the electrical and mechanical activities of cat small intestine.", "content": "Effects of externally applied dopamine and other adrenergic stimulants on the electrical and mechanical activities of the cat small intestine were observed by using pressure electrodes. DOPA and dopamine reduced the spike and mechanical activities. The effects of dopamine were suppressed by treatment with phentolamine, phenoxybenzamine or propranolol. It seems that beta-response is predominant. Noradrenaline and adrenaline also blocked the spike generation and depressed the mechanical activity. Inhibitory actions caused by noradrenaline and adrenaline were blocked by adrenergic blockers. However, no significant effects of normetanephrine and metanephrine were detected. Dose-response curves for acetylcholine with and without dopamine, isoprenaline, phenylephrine and noradrenaline were obtained. The curves with adrenergic stimulants were shifted to higher concentrations of acetylcholine. Possible actions of dompanine were discussed in relation to adrenergic receptors of the cat small intestine. It is concluded that dopamine acts on alpha- and beta-receptors, and separate dopamine receptors could not be proposed by obtianed results.", "contents": "The depressor effect of dopamine on the electrical and mechanical activities of cat small intestine. Effects of externally applied dopamine and other adrenergic stimulants on the electrical and mechanical activities of the cat small intestine were observed by using pressure electrodes. DOPA and dopamine reduced the spike and mechanical activities. The effects of dopamine were suppressed by treatment with phentolamine, phenoxybenzamine or propranolol. It seems that beta-response is predominant. Noradrenaline and adrenaline also blocked the spike generation and depressed the mechanical activity. Inhibitory actions caused by noradrenaline and adrenaline were blocked by adrenergic blockers. However, no significant effects of normetanephrine and metanephrine were detected. Dose-response curves for acetylcholine with and without dopamine, isoprenaline, phenylephrine and noradrenaline were obtained. The curves with adrenergic stimulants were shifted to higher concentrations of acetylcholine. Possible actions of dompanine were discussed in relation to adrenergic receptors of the cat small intestine. It is concluded that dopamine acts on alpha- and beta-receptors, and separate dopamine receptors could not be proposed by obtianed results."}
{"id": "PMID:242102", "title": "An epidemiologic and serologic study of arboviruses in Lake Rudolf basin.", "content": "An epidemiologic and serologic study of arboviruses was done in 1972 in the basin of Lake Rudolf. The main object of this study was to demarcate the southern limit of the yellow fever epidemic which occurred from 1959 to 1962 in Southern Sudan and Ethiopia. Other purposes were to contribute to the inventory of arboviruses and their distribution in this region. The ethnic groups were studied: the Nyangatom and the Dassanetch in Ethiopia and the Turkana in northern Kenya. The results of tests on sera of the Nyangatom and the Dassanetch are practically identical: a high percentage of positive tests for group B. The Turkana on the other hand show a low percentage of positives. This is attributed to differences in the climatic characteristics of the two regions. The serological results suggest the presence of West Nile virus in the geographical areas inhabited by the three ethnic groups. The presence of Wesselsbron and probably Uganda S virus is suspected. Circulation of these viruses could be explained by the presence of Culex univittatus and other mosquitoes. As for yellow fever, the results suggest that the virus did not reach the areas studied, probably because of absence of efficient vectors.", "contents": "An epidemiologic and serologic study of arboviruses in Lake Rudolf basin. An epidemiologic and serologic study of arboviruses was done in 1972 in the basin of Lake Rudolf. The main object of this study was to demarcate the southern limit of the yellow fever epidemic which occurred from 1959 to 1962 in Southern Sudan and Ethiopia. Other purposes were to contribute to the inventory of arboviruses and their distribution in this region. The ethnic groups were studied: the Nyangatom and the Dassanetch in Ethiopia and the Turkana in northern Kenya. The results of tests on sera of the Nyangatom and the Dassanetch are practically identical: a high percentage of positive tests for group B. The Turkana on the other hand show a low percentage of positives. This is attributed to differences in the climatic characteristics of the two regions. The serological results suggest the presence of West Nile virus in the geographical areas inhabited by the three ethnic groups. The presence of Wesselsbron and probably Uganda S virus is suspected. Circulation of these viruses could be explained by the presence of Culex univittatus and other mosquitoes. As for yellow fever, the results suggest that the virus did not reach the areas studied, probably because of absence of efficient vectors."}
{"id": "PMID:242104", "title": "Role of alpha-adrenergic receptor mechanism in closure of the internal urethral orifice during ejaculation.", "content": "The effects of autonomic drugs on closure of the internal urethral orifice during ejaculation were investigated in dogs. The closure of the internal urethral orifice was induced by the electric stimulation of the lateral fibers of the lower mesenteric plexus. The closing state of the orifice was measured with a latex balloon inserted into the orifice. The autonomic drugs were given into the aorta just above its bifurcation. From the results obtained in this study it was concluded that the closure of the internal urethral orifice during ejaculation is predominantly under the influence of the adrenergic nervous system, particularly through an alpha-adrenergic receptor mechanism.", "contents": "Role of alpha-adrenergic receptor mechanism in closure of the internal urethral orifice during ejaculation. The effects of autonomic drugs on closure of the internal urethral orifice during ejaculation were investigated in dogs. The closure of the internal urethral orifice was induced by the electric stimulation of the lateral fibers of the lower mesenteric plexus. The closing state of the orifice was measured with a latex balloon inserted into the orifice. The autonomic drugs were given into the aorta just above its bifurcation. From the results obtained in this study it was concluded that the closure of the internal urethral orifice during ejaculation is predominantly under the influence of the adrenergic nervous system, particularly through an alpha-adrenergic receptor mechanism."}
{"id": "PMID:242105", "title": "Host defense mechanisms in the urinary tract.", "content": "In most episodes of urinary tract infection bacteria reach the bladder through the urethra and then may ascend to the kidneys through the ureters. Bacteria periodically enter the female urinary bladder from the urethra in small numbers. Whether infection ensues depends on the virulence and inoculum size of the microorganism and the adequacy of most defense mechanisms. Human urine is frequently inhibitory and sometimes bactericidal for the bacteria that cause urinary tract infection. Inhibition of bacterial growth coupled with voiding serves as a very effective antibacterial defense mechanism. In addition an intrinsic antibacterial defense mechanism has been demonstrated in the rat urinary bladder unrelated to urine flow. The medulla of the kidney is much more susceptible to infection than the cortex mainly related to its high osmolality. Certain abnormalities of the urinary tract interfere with host defense mechanisms and therefore predispose to urinary tract infection or make infection more difficut to eradicate once present. Some of these abnormalities are obstructive or neurological diseases of the urinary tract, vesicoureteral reflux, calculi, certain metabolic, hematologic, and vascular diseases, and pregnancy.", "contents": "Host defense mechanisms in the urinary tract. In most episodes of urinary tract infection bacteria reach the bladder through the urethra and then may ascend to the kidneys through the ureters. Bacteria periodically enter the female urinary bladder from the urethra in small numbers. Whether infection ensues depends on the virulence and inoculum size of the microorganism and the adequacy of most defense mechanisms. Human urine is frequently inhibitory and sometimes bactericidal for the bacteria that cause urinary tract infection. Inhibition of bacterial growth coupled with voiding serves as a very effective antibacterial defense mechanism. In addition an intrinsic antibacterial defense mechanism has been demonstrated in the rat urinary bladder unrelated to urine flow. The medulla of the kidney is much more susceptible to infection than the cortex mainly related to its high osmolality. Certain abnormalities of the urinary tract interfere with host defense mechanisms and therefore predispose to urinary tract infection or make infection more difficut to eradicate once present. Some of these abnormalities are obstructive or neurological diseases of the urinary tract, vesicoureteral reflux, calculi, certain metabolic, hematologic, and vascular diseases, and pregnancy."}
{"id": "PMID:242107", "title": "[Subastragalar dislocation of the foot].", "content": "An analysis of treatment in 22 patients with foot dislocation in the subastragalar joint is given. In fresh cases the dislocation could be easily reduced in a one-moment procedure under local anesthesia. As evidenced by the authors' findings in later terms arthrodesis of the subastragalar joint after operative correction of the foot deformity seems to be mostly effective.", "contents": "[Subastragalar dislocation of the foot]. An analysis of treatment in 22 patients with foot dislocation in the subastragalar joint is given. In fresh cases the dislocation could be easily reduced in a one-moment procedure under local anesthesia. As evidenced by the authors' findings in later terms arthrodesis of the subastragalar joint after operative correction of the foot deformity seems to be mostly effective."}
{"id": "PMID:242110", "title": "[Acid-base values of porcine blood].", "content": "The main indices of acid-base balance of venous blood (v. auricularis extrema) were determined in 100 clinically disease-free pigs divided into categories with 20 animals each (piglets, pigs from 30 to 40 kg, pigs from 80 to 100 kg, sows, and boars). The Astrup method was employed for the determination of pH, pCO2, total CO2, BE, BB, AB in individuals, groups, and in the set as a whole. The Astrup PHM 71 and BMS 2 apparatuses were used. The results were summed up in a table and in graphs, including the Siggaard-Andersen curve nomogram. Statistical significance was calculated at p greater than 0.05. The average ABB values were determined in the set of 100 pigs; pH 7.306 +/- 0.013, pCO2 53.4 +/- 1.6 mmHg, total CO2 27.6 +/- 0.5, BE --1.0 +/- 0.4, BB 46.2 +/- 0.7, SB 23.5 +/- 0.4, AB 26.0 +/- 0.5 mEl-1.", "contents": "[Acid-base values of porcine blood]. The main indices of acid-base balance of venous blood (v. auricularis extrema) were determined in 100 clinically disease-free pigs divided into categories with 20 animals each (piglets, pigs from 30 to 40 kg, pigs from 80 to 100 kg, sows, and boars). The Astrup method was employed for the determination of pH, pCO2, total CO2, BE, BB, AB in individuals, groups, and in the set as a whole. The Astrup PHM 71 and BMS 2 apparatuses were used. The results were summed up in a table and in graphs, including the Siggaard-Andersen curve nomogram. Statistical significance was calculated at p greater than 0.05. The average ABB values were determined in the set of 100 pigs; pH 7.306 +/- 0.013, pCO2 53.4 +/- 1.6 mmHg, total CO2 27.6 +/- 0.5, BE --1.0 +/- 0.4, BB 46.2 +/- 0.7, SB 23.5 +/- 0.4, AB 26.0 +/- 0.5 mEl-1."}
{"id": "PMID:242111", "title": "[Effect of physical stress on the indices of acid-base homeostasis in pigs].", "content": "Investigated was the effect of physical stress--fixation with a cord at the collection of blood--on the values of the indexes of the acid-base homeostasis of the blood of pigs. It was found out that there existed two types of pigs reacting differently to physical stress. One is a labile type in which, after the stress, there occurs a rapid decrease of the pH of the blood, and the second is a stable type, in which the pH of the blood does not change. The decreasing of the pH in blood is more frequent in younger age categories of fattening pigs and gilts. Application of tranquillizers decreased, to a considerable extent, the occurrence of changes of the acid-base homeostasis of blood.", "contents": "[Effect of physical stress on the indices of acid-base homeostasis in pigs]. Investigated was the effect of physical stress--fixation with a cord at the collection of blood--on the values of the indexes of the acid-base homeostasis of the blood of pigs. It was found out that there existed two types of pigs reacting differently to physical stress. One is a labile type in which, after the stress, there occurs a rapid decrease of the pH of the blood, and the second is a stable type, in which the pH of the blood does not change. The decreasing of the pH in blood is more frequent in younger age categories of fattening pigs and gilts. Application of tranquillizers decreased, to a considerable extent, the occurrence of changes of the acid-base homeostasis of blood."}
{"id": "PMID:242112", "title": "[Study of the enzyme activity of serum cystine aminopeptidase in man and animals in relation to the pH of the medium].", "content": "The authors studied the splitting dynamics of the synthetic chromogenic substrate (S-benzyl-L-cysteine-p-nitroanilide) specific of serum cystine aminopeptidase, depending on a wide range of pH (from 2.5 to 8.0) by means of an enzymatic serum system of pregnant women and selected animals (sheep, cows, sewer-rats), compared with non-pregnant controls. Examining the form of the enzymatic activity curves of the enzymatic system of women's and animal serum in dependence on pH, the authors revealed a characteristic bell-shaped course of the curve in the serum of pregnant women, as distinct from the sera of animals; the activity of cystine aminopeptidase in cows shows a two-peak course at pH from 3.5 to 4.0 and at pH from 6.5 to 7.0 while other animal species show irregularities with signs of the second peak. It follows from the results of the experiment that the main difference between pregnant and control animals is not the general increase of cystine aminopeptidase but a shift of the occurrence, or an increase of enzymatic activity at the given pH. The highest levels of cystine aminopeptidase were found in the blood sera of sewer-rats and lower in sheep and cows.", "contents": "[Study of the enzyme activity of serum cystine aminopeptidase in man and animals in relation to the pH of the medium]. The authors studied the splitting dynamics of the synthetic chromogenic substrate (S-benzyl-L-cysteine-p-nitroanilide) specific of serum cystine aminopeptidase, depending on a wide range of pH (from 2.5 to 8.0) by means of an enzymatic serum system of pregnant women and selected animals (sheep, cows, sewer-rats), compared with non-pregnant controls. Examining the form of the enzymatic activity curves of the enzymatic system of women's and animal serum in dependence on pH, the authors revealed a characteristic bell-shaped course of the curve in the serum of pregnant women, as distinct from the sera of animals; the activity of cystine aminopeptidase in cows shows a two-peak course at pH from 3.5 to 4.0 and at pH from 6.5 to 7.0 while other animal species show irregularities with signs of the second peak. It follows from the results of the experiment that the main difference between pregnant and control animals is not the general increase of cystine aminopeptidase but a shift of the occurrence, or an increase of enzymatic activity at the given pH. The highest levels of cystine aminopeptidase were found in the blood sera of sewer-rats and lower in sheep and cows."}
{"id": "PMID:242113", "title": "[Pathogenesis of aleutian mink disease. VII. Chronic hepatitis with bile duct proliferation].", "content": "Aleutian disease is a chronic persistent viral infection of mink characterized by hypergammaglobulinema, generalized plasmacytosis, sclerosing glomerulonephritis, polyarteritis, and plasma cell hepatitis with bile duct proliferation. The development of hepatic lesions was studied both light- and electron-microscopically in mink experimentally infected with Aleutian disease virus. Fifteen normal and 99 mink experimentally infected with Aleutian disease virus were used. Experimental mink were killed in intervals from 3 weeks to 23 months after infection, and liver sections were processed for both light- and electron-microscopic studies. Experimentally infected mink developed portal and intralobular lymphocytic and plasmacytic infiltrates in the liver 3 weeks after infection. Four to five weeks after infection there was evidence of early bile duct proliferation that began as an outgrowth of the portal bile ducts. Three to five months after infection a marked bile duct proliferation was present in some of the portal triads and adjacent liver lobules; but there was no tendency of these lesions to progress into biliary cirrhosis. Ultrastructural characteristics of proliferating bile duct cells were marked deformation, formation of multiple cell layers, reduction in the number of microvilli and desmosomes, and infiltration of the epithelial cells by lymphoid cells and plasmacytes. The hepatic lesions either develop by direct virus stimulation or by the deposition of virus-antibody complexes.", "contents": "[Pathogenesis of aleutian mink disease. VII. Chronic hepatitis with bile duct proliferation]. Aleutian disease is a chronic persistent viral infection of mink characterized by hypergammaglobulinema, generalized plasmacytosis, sclerosing glomerulonephritis, polyarteritis, and plasma cell hepatitis with bile duct proliferation. The development of hepatic lesions was studied both light- and electron-microscopically in mink experimentally infected with Aleutian disease virus. Fifteen normal and 99 mink experimentally infected with Aleutian disease virus were used. Experimental mink were killed in intervals from 3 weeks to 23 months after infection, and liver sections were processed for both light- and electron-microscopic studies. Experimentally infected mink developed portal and intralobular lymphocytic and plasmacytic infiltrates in the liver 3 weeks after infection. Four to five weeks after infection there was evidence of early bile duct proliferation that began as an outgrowth of the portal bile ducts. Three to five months after infection a marked bile duct proliferation was present in some of the portal triads and adjacent liver lobules; but there was no tendency of these lesions to progress into biliary cirrhosis. Ultrastructural characteristics of proliferating bile duct cells were marked deformation, formation of multiple cell layers, reduction in the number of microvilli and desmosomes, and infiltration of the epithelial cells by lymphoid cells and plasmacytes. The hepatic lesions either develop by direct virus stimulation or by the deposition of virus-antibody complexes."}
{"id": "PMID:242114", "title": "[Influence of gamma-rays on the general acidity and the water-soluble fatty acids of swine and cattle fats].", "content": "Studied were the changes in the total acidity and the amount of the water-soluble fatty acids in bovine and swine fats following the irradiation with gamma-rays. The treatment was effected by means of a 60Co source at 12--15 degrees C. The samples were kept at temperatures ranging from 2 to 4 degrees C, and from --18 to --20 degrees C in the course of 45 and 90 days, resp., being irradiated in the presence and absence of oxygen at rates of from 0.1 up to 2.0 Mrad. Results showed that gamma-treated at the rate of up to 2.00 Mrad produces no effect on the changes observed with the total acidity and the changes taking place during storage. The changes of the water-soluble fatty acids in the presence of oxygen, the type of fat, the temperature value, and the period of storage. The higher the irradiation rates used the greater the changes and shorter the time they need to take place. The presence of oxygen also proved of substantial importance for the changes in the amount of the watersoluble fatty acids. Bovine fats proved more sensitive to the changes referred to than swine fats.", "contents": "[Influence of gamma-rays on the general acidity and the water-soluble fatty acids of swine and cattle fats]. Studied were the changes in the total acidity and the amount of the water-soluble fatty acids in bovine and swine fats following the irradiation with gamma-rays. The treatment was effected by means of a 60Co source at 12--15 degrees C. The samples were kept at temperatures ranging from 2 to 4 degrees C, and from --18 to --20 degrees C in the course of 45 and 90 days, resp., being irradiated in the presence and absence of oxygen at rates of from 0.1 up to 2.0 Mrad. Results showed that gamma-treated at the rate of up to 2.00 Mrad produces no effect on the changes observed with the total acidity and the changes taking place during storage. The changes of the water-soluble fatty acids in the presence of oxygen, the type of fat, the temperature value, and the period of storage. The higher the irradiation rates used the greater the changes and shorter the time they need to take place. The presence of oxygen also proved of substantial importance for the changes in the amount of the watersoluble fatty acids. Bovine fats proved more sensitive to the changes referred to than swine fats."}
{"id": "PMID:242119", "title": "[Mortality due to uremia resulting from chronic kidney diseases].", "content": "The investigation covers the necropsic material of the Pathological Anatomy Chair, Medical Academy-Sofia, with a total of 3519 necropsies for a period of 5 years (1968--1970). In that material, 285 cases with uremia were established, due to chronic renal diseases, which might be referred to 13 nozological entities. The highest number of cases are with chronic pyelonephritis (64,96 per cent). The chronic glomerulonephritis, though it ranks second, is considerably rarely met (9,47 per cent). Endemic nephropathy, according to the incidence, follows--4,21 per cent, nephropathy in diabetes mellitus--3,86 per cent, subacute glomerulonephritis--3,16 per cent, amyloidosis--2,81 per cent, hypertonic disease--2,81 per cent, malignant tumors of the kidneys--2,81 per cent cystic kidneys--2,10 per cent, lupus erythematosus--1,05 per cent, sclerodermia--0,70 per cent, myeloma disease--0,70 per cent and polyarteriitis nodosa--0,35 per cent. As to the chronic renal disease, most frequently met in the material discussed, the chronic pyelonephritis, the authors discuss the factors that played certain role in its development as well.", "contents": "[Mortality due to uremia resulting from chronic kidney diseases]. The investigation covers the necropsic material of the Pathological Anatomy Chair, Medical Academy-Sofia, with a total of 3519 necropsies for a period of 5 years (1968--1970). In that material, 285 cases with uremia were established, due to chronic renal diseases, which might be referred to 13 nozological entities. The highest number of cases are with chronic pyelonephritis (64,96 per cent). The chronic glomerulonephritis, though it ranks second, is considerably rarely met (9,47 per cent). Endemic nephropathy, according to the incidence, follows--4,21 per cent, nephropathy in diabetes mellitus--3,86 per cent, subacute glomerulonephritis--3,16 per cent, amyloidosis--2,81 per cent, hypertonic disease--2,81 per cent, malignant tumors of the kidneys--2,81 per cent cystic kidneys--2,10 per cent, lupus erythematosus--1,05 per cent, sclerodermia--0,70 per cent, myeloma disease--0,70 per cent and polyarteriitis nodosa--0,35 per cent. As to the chronic renal disease, most frequently met in the material discussed, the chronic pyelonephritis, the authors discuss the factors that played certain role in its development as well."}
{"id": "PMID:242121", "title": "[Pulmonary function in papain induced emphysema in dogs (author's tranls)].", "content": "By intratracheal injection of the protease Papain to experimental animals parenchymal changes in the lung can be induced, that resemble human emphysema. Papain (dosage 26 to 112 mg, 1 to 4 injections) was given intratracheally to 8 bastard dogs, (weighing from 12.5 to 20 kg) during light general anesthesia. Pulmonary function was assessed in weekly intervals and related to morphologic changes in the lung. Static compliance of the lung and FRC measured during respiratory arrest were increased after papain, bronchial resistance, measured while artificially ventilated at constant pressure was also increased. Changes of static lung compliance and FRC were seen after the first administration of papain, but further increased with time of observation and after multiple doses of papain. Increase of resistance was not found before 5 weeks. At quiet breathing resistance was not increased at all. No significant changes were found of arterial pO2 and pCO2, pH, standard and actual bicarbonate, diffusion capacity for O2, tidal volume, minute ventilation and ventilatory rate. Morphological findings confirmed the changes described by others. Pulmonary function appears to be pathological at a time when morphology still seems to be normal. The question is discussed to what extent the model of experimental emphysema induced by proteolytic enzymes can contribute to the understanding of human pulmonary emphysema. Lung function in the course of experimental emphysema is compared with function in different clinical types of emphysema.", "contents": "[Pulmonary function in papain induced emphysema in dogs (author's tranls)]. By intratracheal injection of the protease Papain to experimental animals parenchymal changes in the lung can be induced, that resemble human emphysema. Papain (dosage 26 to 112 mg, 1 to 4 injections) was given intratracheally to 8 bastard dogs, (weighing from 12.5 to 20 kg) during light general anesthesia. Pulmonary function was assessed in weekly intervals and related to morphologic changes in the lung. Static compliance of the lung and FRC measured during respiratory arrest were increased after papain, bronchial resistance, measured while artificially ventilated at constant pressure was also increased. Changes of static lung compliance and FRC were seen after the first administration of papain, but further increased with time of observation and after multiple doses of papain. Increase of resistance was not found before 5 weeks. At quiet breathing resistance was not increased at all. No significant changes were found of arterial pO2 and pCO2, pH, standard and actual bicarbonate, diffusion capacity for O2, tidal volume, minute ventilation and ventilatory rate. Morphological findings confirmed the changes described by others. Pulmonary function appears to be pathological at a time when morphology still seems to be normal. The question is discussed to what extent the model of experimental emphysema induced by proteolytic enzymes can contribute to the understanding of human pulmonary emphysema. Lung function in the course of experimental emphysema is compared with function in different clinical types of emphysema."}
{"id": "PMID:242122", "title": "The p-hydroxylation of amphetamine and phentermine by rat liver microsomes.", "content": "1. The products of p-hydroxylation of amphetamine and phentermine by two different preparations of rat liver microsomes were identified and quantitatively determined. At low concentrations (muM) significant proportions of the substrates were metabolized to the p-hydroxy derivatives by an NADPH-dependent system. The enzyme system was inhibited by higher substrate concentrations (mM) and was not induced by either phenobarbital or 3-methylcholanthrene. 2. The properties of this in vitro system are consistent with reports on in vivo studies of this reaction.", "contents": "The p-hydroxylation of amphetamine and phentermine by rat liver microsomes. 1. The products of p-hydroxylation of amphetamine and phentermine by two different preparations of rat liver microsomes were identified and quantitatively determined. At low concentrations (muM) significant proportions of the substrates were metabolized to the p-hydroxy derivatives by an NADPH-dependent system. The enzyme system was inhibited by higher substrate concentrations (mM) and was not induced by either phenobarbital or 3-methylcholanthrene. 2. The properties of this in vitro system are consistent with reports on in vivo studies of this reaction."}
{"id": "PMID:242124", "title": "Effect of mineral acids on iron bacteria.", "content": "The oxidative ability of Thiobacillus ferroxidans in the presence of different concentrations of H2SO4, HC1, HNO3, and their mixtures was investigated. Bacteriological oxidation of FeSO4 is expressed as a function of time and acid concentration. For each acid and for their mixtures lethal concentrations for T. ferroxidans were found experimentally. On the basis of the lethal concentration for each acid separately the lethal concentrations of their mixtures were computed and it was found that they are in good agreement with the experimental data.", "contents": "Effect of mineral acids on iron bacteria. The oxidative ability of Thiobacillus ferroxidans in the presence of different concentrations of H2SO4, HC1, HNO3, and their mixtures was investigated. Bacteriological oxidation of FeSO4 is expressed as a function of time and acid concentration. For each acid and for their mixtures lethal concentrations for T. ferroxidans were found experimentally. On the basis of the lethal concentration for each acid separately the lethal concentrations of their mixtures were computed and it was found that they are in good agreement with the experimental data."}
{"id": "PMID:242125", "title": "[The effect of lumbar peridural anesthesia with catheter on the maternal and fetal acid-base status and the 1 minute apgar score (author's transl)].", "content": "Comparison of 650 deliveries with P.A. and of 928 deliveries without P.A. during the same period. PH from the umbilical artery and 1 minute Apgar score were studied in three groups of patients: 1.) All deliveries, 2.) Spontaneous vaginal deliveries without maternal or fetal risk, 3.) Operative vaginal deliveries. The only significant differences were found among the operative vaginal deliveries: The infants of the peridural group showed a higher incidence of pH-values above 7,2 than those of the non peridural group. Analysis of the maternal acid-base status showed less respiratory alcalosis and less metabolic acidosis in the peridural group. The neonates of this group showed a lower post partum metabolic acidosis than those in the non peridural group.", "contents": "[The effect of lumbar peridural anesthesia with catheter on the maternal and fetal acid-base status and the 1 minute apgar score (author's transl)]. Comparison of 650 deliveries with P.A. and of 928 deliveries without P.A. during the same period. PH from the umbilical artery and 1 minute Apgar score were studied in three groups of patients: 1.) All deliveries, 2.) Spontaneous vaginal deliveries without maternal or fetal risk, 3.) Operative vaginal deliveries. The only significant differences were found among the operative vaginal deliveries: The infants of the peridural group showed a higher incidence of pH-values above 7,2 than those of the non peridural group. Analysis of the maternal acid-base status showed less respiratory alcalosis and less metabolic acidosis in the peridural group. The neonates of this group showed a lower post partum metabolic acidosis than those in the non peridural group."}
{"id": "PMID:242126", "title": "A rare type of low birthweight dwarfism: the Dubowitz syndrome.", "content": "Two patients with the Dubowitz syndrome are presented. This presumably recessive inherited syndrome was first defined by Grosse et al. (1971). So far 11 patients with this syndrome have been described. Major clinical findings are intrauterine and postnatal growth retardation, considerable microcephaly, mild mental retardation, hyperactivity, hyperextensibility of joints, eczema and a characteristic appearance of the face due to marked epicanthic folds, blepharophimosis, broadening of the bridge and tip of the nose and retrognathia. Minor anomalies as clinodactylyl of the firth digits, cutaneous syndactyly of toes, foot deformity, sacral dimple and cryptorchidism may be seen. The exclusion of the non genetic fetal alcohol syndrome presents serious diagnostic problems.", "contents": "A rare type of low birthweight dwarfism: the Dubowitz syndrome. Two patients with the Dubowitz syndrome are presented. This presumably recessive inherited syndrome was first defined by Grosse et al. (1971). So far 11 patients with this syndrome have been described. Major clinical findings are intrauterine and postnatal growth retardation, considerable microcephaly, mild mental retardation, hyperactivity, hyperextensibility of joints, eczema and a characteristic appearance of the face due to marked epicanthic folds, blepharophimosis, broadening of the bridge and tip of the nose and retrognathia. Minor anomalies as clinodactylyl of the firth digits, cutaneous syndactyly of toes, foot deformity, sacral dimple and cryptorchidism may be seen. The exclusion of the non genetic fetal alcohol syndrome presents serious diagnostic problems."}
{"id": "PMID:242127", "title": "[Optimized determination and properties of NADPH-dependent glutathione reductase in serum. Studies on serum glutathione reductase, I. (author's transl)].", "content": "Reaction conditions were optimized for the determination of serum glutathione reductase, which has not yet been investigated systematically. Imidazole was found to be the most suitable buffer material; the highest glutathione reductase activity in serum was always obtained with imidazole/HCl buffer, which, in contrast to all other tested buffers, also resulted in the maximal enzyme activity without preincubation. In imidazole buffer, the pH-activity curve of serum glutathione reductase shows a broad optimum between pH 6.5 and 6.9. A GSSG concentration of 2 mmol/l and a NADPH concentration of 0.43 mmol/l gave maximal enzyme activity and a linear reaction over 10 min up to 20 U/l test solution. An investigation of serum glutathione reductase activity from 100 clinically healthy probands gave values between 20 and 50 U/l. In the optimized assay system the glutathione reductase in the serum reacts specifically with GSSG and NADPH.", "contents": "[Optimized determination and properties of NADPH-dependent glutathione reductase in serum. Studies on serum glutathione reductase, I. (author's transl)]. Reaction conditions were optimized for the determination of serum glutathione reductase, which has not yet been investigated systematically. Imidazole was found to be the most suitable buffer material; the highest glutathione reductase activity in serum was always obtained with imidazole/HCl buffer, which, in contrast to all other tested buffers, also resulted in the maximal enzyme activity without preincubation. In imidazole buffer, the pH-activity curve of serum glutathione reductase shows a broad optimum between pH 6.5 and 6.9. A GSSG concentration of 2 mmol/l and a NADPH concentration of 0.43 mmol/l gave maximal enzyme activity and a linear reaction over 10 min up to 20 U/l test solution. An investigation of serum glutathione reductase activity from 100 clinically healthy probands gave values between 20 and 50 U/l. In the optimized assay system the glutathione reductase in the serum reacts specifically with GSSG and NADPH."}
{"id": "PMID:242128", "title": "Serum dopamine beta-hydroxylase: assay and enzyme properties.", "content": "A method for the estimation of dopamine beta-hydroxylase activity in human serum is described, based on a thin layer chromatographic separation of the substrate ([14C]tyramine) from the reaction product ([14C]octopamine). The basic properties of the human serum enzyme, investigated by this method are described.", "contents": "Serum dopamine beta-hydroxylase: assay and enzyme properties. A method for the estimation of dopamine beta-hydroxylase activity in human serum is described, based on a thin layer chromatographic separation of the substrate ([14C]tyramine) from the reaction product ([14C]octopamine). The basic properties of the human serum enzyme, investigated by this method are described."}
{"id": "PMID:242129", "title": "Serum alpha-N-acetylglucosaminidase: determination, characterization, and corrective activity in Sanifilippo B fibroblasts.", "content": "Assays for the determination of serum alpha-N-acetylglucosaminidase (EC 3.2.1.50) activity are described employing p-nitrophenyl-N-acetyl-alpha-D-glucosaminide, phenyl-N-acetyl-alpha-D-glucosaminide, and UDP-N-acetylglucosamine as substrates. A log normal distribution of the serum enzyme activity was found. The determination of serum alpha-N-acetylglucosaminidase activity proved to be a valuable tool for the recognition of homozygous and heterozygous carriers of the Sanfilippo B gene.", "contents": "Serum alpha-N-acetylglucosaminidase: determination, characterization, and corrective activity in Sanifilippo B fibroblasts. Assays for the determination of serum alpha-N-acetylglucosaminidase (EC 3.2.1.50) activity are described employing p-nitrophenyl-N-acetyl-alpha-D-glucosaminide, phenyl-N-acetyl-alpha-D-glucosaminide, and UDP-N-acetylglucosamine as substrates. A log normal distribution of the serum enzyme activity was found. The determination of serum alpha-N-acetylglucosaminidase activity proved to be a valuable tool for the recognition of homozygous and heterozygous carriers of the Sanfilippo B gene."}
{"id": "PMID:242130", "title": "The effect of heavy metal ions on the rate of decomposition of N-ethyl-N-nitrosourea and other carcinogenic N-nitrosamides.", "content": "The decomposition of ethylnitrosourea (ENU) in aqueous solution is enhanced by Cu2+ ions. Ni2+ shows a similar, but less pronounced effect. The decomposition rate of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a compound known to be relatively stable in aqueous solution, is strongly enhanced by the addition of Cu2+ and to a smaller extent also by Ni2+ ions. On the other hand the stability of N-methyl-N-nitrosourethane is not influenced by heavy meatal ions. The influence of Cu2+ ions on the decomposition rate of ENU is similar to that of OH-anions, influencing the reaction kinetics on a molar basis. The increase in decomposition rate of ENU by copper ions is not seen in the presence of blood serum or other complexing agents. The results are discussed in relation to the known enhancement in toxicity and carcinogenicity of ENU by heavy metal salts in animal experiments.", "contents": "The effect of heavy metal ions on the rate of decomposition of N-ethyl-N-nitrosourea and other carcinogenic N-nitrosamides. The decomposition of ethylnitrosourea (ENU) in aqueous solution is enhanced by Cu2+ ions. Ni2+ shows a similar, but less pronounced effect. The decomposition rate of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a compound known to be relatively stable in aqueous solution, is strongly enhanced by the addition of Cu2+ and to a smaller extent also by Ni2+ ions. On the other hand the stability of N-methyl-N-nitrosourethane is not influenced by heavy meatal ions. The influence of Cu2+ ions on the decomposition rate of ENU is similar to that of OH-anions, influencing the reaction kinetics on a molar basis. The increase in decomposition rate of ENU by copper ions is not seen in the presence of blood serum or other complexing agents. The results are discussed in relation to the known enhancement in toxicity and carcinogenicity of ENU by heavy metal salts in animal experiments."}
{"id": "PMID:242131", "title": "[Gelelectrofocusing of protektin anti AHP from the albumin gland of Helix pomatia (author's transl)].", "content": "The protektin anti AHP from the albumine gland of Helix pomatia is a very interesting substance because of its ability to agglutinate erythrocytes of blood group A as well as group C streptococci. Purification is possible by reversible absorption on Sephadex G200. Isoelectric focusing in a sucrose density gradient is difficult, because the protein precipitates at the isoelectric point. The agglutinin, which is homogeneous in disk electrophoresis experiments (in an alkaline gel system as well as in an acidic one), shows around 9 bands in gelelectrofocusing. All components are able to agglutinate group C-streptococci. Complex formation between protein and ampholytes has been excluded by experiments in gels containing 7M urea. The region of the isoelectric points of the components is between pH 6 and pH 8. The inhomogeneity in gelelectrofocusing is caused probably by differences in the subunits of the protein molecule.", "contents": "[Gelelectrofocusing of protektin anti AHP from the albumin gland of Helix pomatia (author's transl)]. The protektin anti AHP from the albumine gland of Helix pomatia is a very interesting substance because of its ability to agglutinate erythrocytes of blood group A as well as group C streptococci. Purification is possible by reversible absorption on Sephadex G200. Isoelectric focusing in a sucrose density gradient is difficult, because the protein precipitates at the isoelectric point. The agglutinin, which is homogeneous in disk electrophoresis experiments (in an alkaline gel system as well as in an acidic one), shows around 9 bands in gelelectrofocusing. All components are able to agglutinate group C-streptococci. Complex formation between protein and ampholytes has been excluded by experiments in gels containing 7M urea. The region of the isoelectric points of the components is between pH 6 and pH 8. The inhomogeneity in gelelectrofocusing is caused probably by differences in the subunits of the protein molecule."}
{"id": "PMID:242132", "title": "[Giant-cell (Takayasu) arteritis as a cause of renovascular hypertension].", "content": "In a young female with renovascular hypertension multiple stenoses affecting both renal arteries, abdominal aorta and left axillary artery could be demonstrated. The elevated blood pressure could be normalized by bypass operation of the renal arteries. Histopathologic findings were those of giant cell (Takayasu) arteritis.", "contents": "[Giant-cell (Takayasu) arteritis as a cause of renovascular hypertension]. In a young female with renovascular hypertension multiple stenoses affecting both renal arteries, abdominal aorta and left axillary artery could be demonstrated. The elevated blood pressure could be normalized by bypass operation of the renal arteries. Histopathologic findings were those of giant cell (Takayasu) arteritis."}
{"id": "PMID:242135", "title": "[The hatching of the eggs of the liver fluke Fasciola hepatica L. under various CO2-concentrations (author's transl)].", "content": "The presupposition for the hatching of the eggs of Fasciola hepatica is the presence of undissociated CO2 with the most effective concentration of 2-10 mMols/l. Higher concentrations show inhibitory effects (Abb. 6). In hatching pH has only importance in dissociation of carbonic acid and so in maintaining free CO2. To provide for sufficient CO2 at higher pH - but below 8.3 - the concentration of carbonic acid must be increased by higher concentrations of metallic ions electrically neutralized by hydrogen carbonate (e.g. in Abb. 1-4). Higher pH is necessary for miracidia surviving. Beside the wellknown hatching factors of exposure to light and cooling, darkening is a new found factor (s. Abb. 7) as well as sufficient increase of CO2 itself. The effect of light stimulation is lasting for at most 3 h with exponential decrease (Abb. 7). At low CO2-pressure the occurrence of hatching is greater without any oxygen (Abb. 5).", "contents": "[The hatching of the eggs of the liver fluke Fasciola hepatica L. under various CO2-concentrations (author's transl)]. The presupposition for the hatching of the eggs of Fasciola hepatica is the presence of undissociated CO2 with the most effective concentration of 2-10 mMols/l. Higher concentrations show inhibitory effects (Abb. 6). In hatching pH has only importance in dissociation of carbonic acid and so in maintaining free CO2. To provide for sufficient CO2 at higher pH - but below 8.3 - the concentration of carbonic acid must be increased by higher concentrations of metallic ions electrically neutralized by hydrogen carbonate (e.g. in Abb. 1-4). Higher pH is necessary for miracidia surviving. Beside the wellknown hatching factors of exposure to light and cooling, darkening is a new found factor (s. Abb. 7) as well as sufficient increase of CO2 itself. The effect of light stimulation is lasting for at most 3 h with exponential decrease (Abb. 7). At low CO2-pressure the occurrence of hatching is greater without any oxygen (Abb. 5)."}
{"id": "PMID:242136", "title": "Monoxenic and axenic cultivation of carrier and patient strains of Entamoeba histolytica.", "content": "All of five strains of Entamoeba histolytica, isolated from symptomatic cases of amoebiasis, could be adapted to axenic growth on the TP-S-1 medium of Diamond (1968). Four axenic strains were started from amoeba-Crithidia cultures; one could be axenized directly after isolation from a case of cutaneous amoebiasis. Attempts to monoxenize, resp. axenize strains, isolated from Dutch, asymptomatic carriers, were less successful. Only three out of ten strains could be submitted to bacteria-free growth. These three strains, however, originated probably from a recent case of intestinal amoebiasis. The results, suggesting that highly virulent strains can be easier cultivated bacteria-free than those with low or no virulence, are further discussed. The yield of axenic amoebae per tube fluctuates largely depending on many factors such as the strain, the number of transfers (i.e. degree of establishment), the quality of Panmede liver digest and serum in the TP-S-1 medium, and the care of manipulating the cultures. For optimal growth, a more acid medium was required  in an amoeba-Crithidia culture than in an axenic culture. Multinucleated, giant amoebae were frequently observed in axenic cultures.", "contents": "Monoxenic and axenic cultivation of carrier and patient strains of Entamoeba histolytica. All of five strains of Entamoeba histolytica, isolated from symptomatic cases of amoebiasis, could be adapted to axenic growth on the TP-S-1 medium of Diamond (1968). Four axenic strains were started from amoeba-Crithidia cultures; one could be axenized directly after isolation from a case of cutaneous amoebiasis. Attempts to monoxenize, resp. axenize strains, isolated from Dutch, asymptomatic carriers, were less successful. Only three out of ten strains could be submitted to bacteria-free growth. These three strains, however, originated probably from a recent case of intestinal amoebiasis. The results, suggesting that highly virulent strains can be easier cultivated bacteria-free than those with low or no virulence, are further discussed. The yield of axenic amoebae per tube fluctuates largely depending on many factors such as the strain, the number of transfers (i.e. degree of establishment), the quality of Panmede liver digest and serum in the TP-S-1 medium, and the care of manipulating the cultures. For optimal growth, a more acid medium was required  in an amoeba-Crithidia culture than in an axenic culture. Multinucleated, giant amoebae were frequently observed in axenic cultures."}
{"id": "PMID:242137", "title": "Studies on the excystment of trematode metacercariae in vitro.", "content": "Excystment of metacercariae of Parorchis acanthus, Posthodiplostomoides leonensis, Posthodiplostomum sp. and Clinostomum tilapiae was found to be an active process initiated by the metacercariae when the correct physico-chemical conditions exist in the environment; but in the excystment of Posthodiplostomum nanum the metacercaria seems not to take part in the process. Temperature, osmotic pressure, pH and eH are factors which influence all the five species studied. Fresh ox bile was found not to be an absolute necessity for the excystment of the five species studied but its presence in the medium increased the rate of excystment of three species.", "contents": "Studies on the excystment of trematode metacercariae in vitro. Excystment of metacercariae of Parorchis acanthus, Posthodiplostomoides leonensis, Posthodiplostomum sp. and Clinostomum tilapiae was found to be an active process initiated by the metacercariae when the correct physico-chemical conditions exist in the environment; but in the excystment of Posthodiplostomum nanum the metacercaria seems not to take part in the process. Temperature, osmotic pressure, pH and eH are factors which influence all the five species studied. Fresh ox bile was found not to be an absolute necessity for the excystment of the five species studied but its presence in the medium increased the rate of excystment of three species."}
{"id": "PMID:242138", "title": "A comparative study of the two alternative larval forms of Hymenolepis nana, the dwarf tapeworm, with special reference to the process of excystment.", "content": "Studies of the cysticercoids of Hymenolepis nana from insects and from mouse villi revealed important differences in cyst structure and function. The insect form resists low pH unless treated with bile salts which render the cyst permeable and reduce infectivity to mice. Bile salts are not essential for scolex activation. Activation is inhibited by pH 2.5 and under and by 1% succinic acid up to pH 4.0. The importance of scolex immobility and energy conservation in relation to cyst impermeability is discussed. The villus cysticercoid has no special insulating layer. It is vulnerable to low pH and cannot infect mice orally. Bile salts are without effect and excystment occurs unaided by external agents. The structural differences between the two forms revealed by the electron microscope may be attributed to changes in the relative rates of development of the various tissues.", "contents": "A comparative study of the two alternative larval forms of Hymenolepis nana, the dwarf tapeworm, with special reference to the process of excystment. Studies of the cysticercoids of Hymenolepis nana from insects and from mouse villi revealed important differences in cyst structure and function. The insect form resists low pH unless treated with bile salts which render the cyst permeable and reduce infectivity to mice. Bile salts are not essential for scolex activation. Activation is inhibited by pH 2.5 and under and by 1% succinic acid up to pH 4.0. The importance of scolex immobility and energy conservation in relation to cyst impermeability is discussed. The villus cysticercoid has no special insulating layer. It is vulnerable to low pH and cannot infect mice orally. Bile salts are without effect and excystment occurs unaided by external agents. The structural differences between the two forms revealed by the electron microscope may be attributed to changes in the relative rates of development of the various tissues."}
{"id": "PMID:242141", "title": "[Phospholipase D of cereals (author's transl)].", "content": "Phospholipase D containing water insoluble fraction was isolated from mature barley; the enzym preparation only had weak phospholipase B activity. The phospholipase D of barley was activated by Ca2+, diethyl ether and sodium dodecyl sulphate (SDS); EDTA inhibited the enzyme to an extent of 10% of the original activity. Diethyl ether and SDS showed and additive effect. Phospholipase D activated by CaC12, diethyl ether and SDS exhibited a sharp optimum at pH 6.6. Lysophosphatidylcholine was hydrolysed much slower than phosphatidylcholine. Diethyl ether and SDS also increased the breakdown of the lysophosphatidylcholine.", "contents": "[Phospholipase D of cereals (author's transl)]. Phospholipase D containing water insoluble fraction was isolated from mature barley; the enzym preparation only had weak phospholipase B activity. The phospholipase D of barley was activated by Ca2+, diethyl ether and sodium dodecyl sulphate (SDS); EDTA inhibited the enzyme to an extent of 10% of the original activity. Diethyl ether and SDS showed and additive effect. Phospholipase D activated by CaC12, diethyl ether and SDS exhibited a sharp optimum at pH 6.6. Lysophosphatidylcholine was hydrolysed much slower than phosphatidylcholine. Diethyl ether and SDS also increased the breakdown of the lysophosphatidylcholine."}
{"id": "PMID:242142", "title": "Mitochondrial enzyme pathways and their possible role during curing.", "content": "The velocity of oxidation of exogenous ferrocytochrome c by nitrite under anaerobic conditions in the presence of skeletal muscle mitochondria is dependent upon pH over at least the range 5.6-6.7, increasing markedly as the pH is lowered. A product of the reaction is the complex formed between nitric oxide and ferricytochrome c. At levels up to 20 mM, nitrite inhibits aerobic cytochrome oxidase action; at higher concentrations, however, a partial resuscitation of the oxidation of ferrocytochrome c occurs, the enhancement of reaction velocity being considerably greater at pH 6.0 than at 6.5. Mitochondrial respiration is also inhibited by nitrite but no similar resurgence was, however, observed and thus the oxidation of ferrocytochrome c by high levels of nitrite is considered to be a direct non-enzymic action. Under anaerobic conditions, the rate of increase of the velocity constant of the oxidation of ferrocytochrome c with nitrite concentration in the presence of muscle mitochondria similarly decreased with rise of pH over the same range. The permeability of the muscle mitochondrion to nitrire has been demonstrated by swelling studies and by the rapid conversion of endogenous ferrocytochrome a3 into its nitrosyl-derivative. Over longer periods of anaerobic incubations of mitochondria with nitrite, oxidation of endogenous cytochromes occurs with the formation of nitrosylferricytochrome c. Above a nitrite concentration of 0.3 mM, the mitochondrial enzyme system probably involved is increasingly inhibited but by a concentration of 30 mM a direct non-enzymic oxidation has intervened. Commercial vacuum packed bacons were examined by electron microscopy. Mitochondria were clearly recognisable although they contained fewer cristae than those observed in fresh meat.", "contents": "Mitochondrial enzyme pathways and their possible role during curing. The velocity of oxidation of exogenous ferrocytochrome c by nitrite under anaerobic conditions in the presence of skeletal muscle mitochondria is dependent upon pH over at least the range 5.6-6.7, increasing markedly as the pH is lowered. A product of the reaction is the complex formed between nitric oxide and ferricytochrome c. At levels up to 20 mM, nitrite inhibits aerobic cytochrome oxidase action; at higher concentrations, however, a partial resuscitation of the oxidation of ferrocytochrome c occurs, the enhancement of reaction velocity being considerably greater at pH 6.0 than at 6.5. Mitochondrial respiration is also inhibited by nitrite but no similar resurgence was, however, observed and thus the oxidation of ferrocytochrome c by high levels of nitrite is considered to be a direct non-enzymic action. Under anaerobic conditions, the rate of increase of the velocity constant of the oxidation of ferrocytochrome c with nitrite concentration in the presence of muscle mitochondria similarly decreased with rise of pH over the same range. The permeability of the muscle mitochondrion to nitrire has been demonstrated by swelling studies and by the rapid conversion of endogenous ferrocytochrome a3 into its nitrosyl-derivative. Over longer periods of anaerobic incubations of mitochondria with nitrite, oxidation of endogenous cytochromes occurs with the formation of nitrosylferricytochrome c. Above a nitrite concentration of 0.3 mM, the mitochondrial enzyme system probably involved is increasingly inhibited but by a concentration of 30 mM a direct non-enzymic oxidation has intervened. Commercial vacuum packed bacons were examined by electron microscopy. Mitochondria were clearly recognisable although they contained fewer cristae than those observed in fresh meat."}
{"id": "PMID:242159", "title": "[Contribution to postmortem diagnostics of poisoning due to insulin (author's transl)].", "content": "In a case of lethal poisoning due to insulin a significant low level of lactic acid and a corresponding high pH value in the brain tissue were detected. Methods used to determine lactic acid and pH in the brain tissue are recommeded for postmortem diagnostics of insulin poisoning.", "contents": "[Contribution to postmortem diagnostics of poisoning due to insulin (author's transl)]. In a case of lethal poisoning due to insulin a significant low level of lactic acid and a corresponding high pH value in the brain tissue were detected. Methods used to determine lactic acid and pH in the brain tissue are recommeded for postmortem diagnostics of insulin poisoning."}
{"id": "PMID:242162", "title": "[The significance of meconium-containing amniotic fluid at the onset of labor following a normal pregnancy].", "content": "The delivery process of 218 gravids admitted after a normal course of pregnancy with meconium containing amniotic fluid are analysed. The higher operative frequency (25,2%) in comparison with the test group (10,9%) and the fact that in 4 fetuses the pH value on admission was under 7,20 confirm the recommendation to make obligatory the admission amnioscopy of all gravids at the beginning of birth. This practice involves continuous medical shift work. The perinatal mortality of the analysed deliveries was 0,46%.", "contents": "[The significance of meconium-containing amniotic fluid at the onset of labor following a normal pregnancy]. The delivery process of 218 gravids admitted after a normal course of pregnancy with meconium containing amniotic fluid are analysed. The higher operative frequency (25,2%) in comparison with the test group (10,9%) and the fact that in 4 fetuses the pH value on admission was under 7,20 confirm the recommendation to make obligatory the admission amnioscopy of all gravids at the beginning of birth. This practice involves continuous medical shift work. The perinatal mortality of the analysed deliveries was 0,46%."}
{"id": "PMID:242163", "title": "[Determination of bilirubin in the amniotic fluid by means of the chloroform-extraction method].", "content": "A reproducible method for the determination of bilirubin in amniotic fluid by measuring the extinction of the the chloroform extract is described. The measurements can be carried out by means of a simple spectrophotometer. In case of extraction of amniotic fluid containing blood informative results are obtained as well. Since the extinction values are equal to the deltaE-values it is possible to determine the degree of morbus haemolyticus fetalis using the schema of Liley.", "contents": "[Determination of bilirubin in the amniotic fluid by means of the chloroform-extraction method]. A reproducible method for the determination of bilirubin in amniotic fluid by measuring the extinction of the the chloroform extract is described. The measurements can be carried out by means of a simple spectrophotometer. In case of extraction of amniotic fluid containing blood informative results are obtained as well. Since the extinction values are equal to the deltaE-values it is possible to determine the degree of morbus haemolyticus fetalis using the schema of Liley."}
{"id": "PMID:242164", "title": "[Emissions from combustion of indoor dust (author's transl)].", "content": "Combustion of dust is an old problem which has gained a new importance since the introduction of electric storage heaters for space heating. Physico-chemical changes caused by heating indoor dust in a model apparatus were investigated. Four dust samples of different origins were heated at three temperatures (200, 400, 600 degrees C) for three residence times (5, 15, 30 min). The higher the temperature, the higher the weight loss expressed as percentage (15 to 75%). The residence time had no effect on the loss. Three dust samples showed pH of about 7 before heated, while the fourth showed pH of about 10. After heating to 200 degrees C, the pH of one of the samples rose from 7 to 10. When heated to 400 and 600 degrees C, all the samples showed pH values between 10 and 11. The residence time had no effect. The pH of the gaseous reaction products did not show uniform pattern at 200 degrees C. At 400 degrees C, the measured pH was between 7.5 and 8.5, while at 600 degrees C no further change was observed. Changes in pH took place during the first fifteen minutes. Chemical analysis of the reaction products with help of detector tubes indicated that dust samples when heated emit carbon monoxide, carbon dioxide, oxides of nitrogen and ammonia.", "contents": "[Emissions from combustion of indoor dust (author's transl)]. Combustion of dust is an old problem which has gained a new importance since the introduction of electric storage heaters for space heating. Physico-chemical changes caused by heating indoor dust in a model apparatus were investigated. Four dust samples of different origins were heated at three temperatures (200, 400, 600 degrees C) for three residence times (5, 15, 30 min). The higher the temperature, the higher the weight loss expressed as percentage (15 to 75%). The residence time had no effect on the loss. Three dust samples showed pH of about 7 before heated, while the fourth showed pH of about 10. After heating to 200 degrees C, the pH of one of the samples rose from 7 to 10. When heated to 400 and 600 degrees C, all the samples showed pH values between 10 and 11. The residence time had no effect. The pH of the gaseous reaction products did not show uniform pattern at 200 degrees C. At 400 degrees C, the measured pH was between 7.5 and 8.5, while at 600 degrees C no further change was observed. Changes in pH took place during the first fifteen minutes. Chemical analysis of the reaction products with help of detector tubes indicated that dust samples when heated emit carbon monoxide, carbon dioxide, oxides of nitrogen and ammonia."}
{"id": "PMID:242165", "title": "[Glass fibre HEPA filters. II. Communication: Microbiological and physico-chemical researchs on used and unusued, hydrophilic and hydrophobic filter materials in an air conditioning plant (author's transl)].", "content": "Hydrophobic and hydrophilic, used and unused HEPA filters from various manufacturers, inoculated with vegetative bacteria, bacterial and fungal spores, were exposed to clean outside air for up to 17 weeks in an air conditioning plant. With relative humidities up to 60%, an increase in germ count could not be found. The rate of killing the micro-organisms inoculated were different and were generally higher on used filters. The low water content of the filter material was apparently not sufficient for microbial growth. In addition, the increase in electric conductivity and reduction of pH value resulting from deposition of substances from the outside air with an acid reaction ascertained in the aqueous filter extracts had a negative effect on the living conditions of the microorganisms.", "contents": "[Glass fibre HEPA filters. II. Communication: Microbiological and physico-chemical researchs on used and unusued, hydrophilic and hydrophobic filter materials in an air conditioning plant (author's transl)]. Hydrophobic and hydrophilic, used and unused HEPA filters from various manufacturers, inoculated with vegetative bacteria, bacterial and fungal spores, were exposed to clean outside air for up to 17 weeks in an air conditioning plant. With relative humidities up to 60%, an increase in germ count could not be found. The rate of killing the micro-organisms inoculated were different and were generally higher on used filters. The low water content of the filter material was apparently not sufficient for microbial growth. In addition, the increase in electric conductivity and reduction of pH value resulting from deposition of substances from the outside air with an acid reaction ascertained in the aqueous filter extracts had a negative effect on the living conditions of the microorganisms."}
{"id": "PMID:242166", "title": "[Metabolism of rat liver in the electrostatic field and in the faraday cage before and after hepatectomy (author's transl)].", "content": "Investigations were performed with the aim of establishing the influence of various environmental conditions (such as steady field conditions, climatized laboratories, Faraday's cage) on a number of enzymic activities in the rat (including glutamic oxaloacetic tic transaminase, glutamic pyruvic transaminase, lactic dehydrogenase, gamma-glutamyl transpeptidase, acid phosphatase), as well as the serum concentrations of triglycerides, the oxygen consumption of hepatic parenchyma cells, and the influence on the incorporation of 3H-thymidine (following partial hepatectomy). In the steady field, the activities of the cytoplasmic enzymes (GOT, GPT, LDH) were higher then under Faraday conditions. The same applies both to the hepatic oxygen consumption and to the neutral fat serum levels. The control values always remained within the range of the results obtained under steady field or Faraday conditions. In the structure-linked enzymes (gamma-glutamyl transpeptidase, acid phosphatase) the results were not uniform. Following partial hepatectomy, and under steady field conditions, the serum triglyceride concentrations showed a less pronounced drop than they did in the controls. Under selected environmental conditions, the results obtained lie within the physiological range. The present findings, therefore, do not permit definite conclusions to be drawn on favourable or unfavourable effects exerted by the different types of electroclimates.", "contents": "[Metabolism of rat liver in the electrostatic field and in the faraday cage before and after hepatectomy (author's transl)]. Investigations were performed with the aim of establishing the influence of various environmental conditions (such as steady field conditions, climatized laboratories, Faraday's cage) on a number of enzymic activities in the rat (including glutamic oxaloacetic tic transaminase, glutamic pyruvic transaminase, lactic dehydrogenase, gamma-glutamyl transpeptidase, acid phosphatase), as well as the serum concentrations of triglycerides, the oxygen consumption of hepatic parenchyma cells, and the influence on the incorporation of 3H-thymidine (following partial hepatectomy). In the steady field, the activities of the cytoplasmic enzymes (GOT, GPT, LDH) were higher then under Faraday conditions. The same applies both to the hepatic oxygen consumption and to the neutral fat serum levels. The control values always remained within the range of the results obtained under steady field or Faraday conditions. In the structure-linked enzymes (gamma-glutamyl transpeptidase, acid phosphatase) the results were not uniform. Following partial hepatectomy, and under steady field conditions, the serum triglyceride concentrations showed a less pronounced drop than they did in the controls. Under selected environmental conditions, the results obtained lie within the physiological range. The present findings, therefore, do not permit definite conclusions to be drawn on favourable or unfavourable effects exerted by the different types of electroclimates."}
{"id": "PMID:242167", "title": "[Report of \"lethal factor\" synthetized by Bacillus cereus (author's transl)].", "content": "Bacillus cereus growing in nutrition broth produces during logarithmic growth and in stationary phase a lethal factor extremely toxic for rodents. This toxin is only produced in the presence of oxygen and depends on bacterial replication. The highest titers of toxin are obtained using bacteria in a concentration of 10(7) to 10(9) per ml of nutrition broth. During regression phase of Bacillus cereus the titer of toxin declines to zero. Toxicity of the lethal factor becomes not altered in an alcaline or acidic medium. Temperatures exceeding 65 degrees C inactivate the toxin indicating its thermolability. Oral and rectal dispension of large quantities of the lethal factor does not induce toxic symptoms in rodents. However, when applicating toxin containing cultural filtrate of Bacillus cereus as an i.v., i.p., i.n. or s.c. injection it becomes highly toxic for mice, rats, hamsters, guinea pigs and rabbits. All animals injected by the different ways parenterally died.", "contents": "[Report of \"lethal factor\" synthetized by Bacillus cereus (author's transl)]. Bacillus cereus growing in nutrition broth produces during logarithmic growth and in stationary phase a lethal factor extremely toxic for rodents. This toxin is only produced in the presence of oxygen and depends on bacterial replication. The highest titers of toxin are obtained using bacteria in a concentration of 10(7) to 10(9) per ml of nutrition broth. During regression phase of Bacillus cereus the titer of toxin declines to zero. Toxicity of the lethal factor becomes not altered in an alcaline or acidic medium. Temperatures exceeding 65 degrees C inactivate the toxin indicating its thermolability. Oral and rectal dispension of large quantities of the lethal factor does not induce toxic symptoms in rodents. However, when applicating toxin containing cultural filtrate of Bacillus cereus as an i.v., i.p., i.n. or s.c. injection it becomes highly toxic for mice, rats, hamsters, guinea pigs and rabbits. All animals injected by the different ways parenterally died."}
{"id": "PMID:242168", "title": "[Polarographic studies on the peroxidase activity of liganded deuterohemin].", "content": "The peroxidase activity of deuterohemin and deuterohemin complexes relative to the substrates pyrogallol and ascorbic acid was studied using d.c. polarography in aqueous solution. Imidazole and pyridine served as complex ligands. In the absence of the ligands, a continual rise in the substrate conversion rate with increasing H2O2 initial concentration is observed. Imidazole or pyridine were found to considerably increase the peroxidase activity of deuterohemin at low H2O2 concentrations. At high H2O2 concentrations, the dependence of the reaction rate on H2O2 concentration shows a bend, the reaction rate being in each case higher than that of free hemin under the same conditions. The reason of this fact is discussed to be a retarded formation of activated H2O2 hemin-ligand complexes at high H2O2 concentrations.", "contents": "[Polarographic studies on the peroxidase activity of liganded deuterohemin]. The peroxidase activity of deuterohemin and deuterohemin complexes relative to the substrates pyrogallol and ascorbic acid was studied using d.c. polarography in aqueous solution. Imidazole and pyridine served as complex ligands. In the absence of the ligands, a continual rise in the substrate conversion rate with increasing H2O2 initial concentration is observed. Imidazole or pyridine were found to considerably increase the peroxidase activity of deuterohemin at low H2O2 concentrations. At high H2O2 concentrations, the dependence of the reaction rate on H2O2 concentration shows a bend, the reaction rate being in each case higher than that of free hemin under the same conditions. The reason of this fact is discussed to be a retarded formation of activated H2O2 hemin-ligand complexes at high H2O2 concentrations."}
{"id": "PMID:242169", "title": "[The effect of the immobilization of hemoglobin on its oxygen binding].", "content": "Hemoglobin (Hb) covalently fixed to CM-Sephadex was found to bind oxygen in weakly acidic medium with higher affinity than free Hb. The opposite relation is seen in the alkaline pH region. The alkaline Bohr effect was determined to be -0.2 only. Cooperativity is pH dependent. The sigmoid coefficient at pH 6 is 0.7; at pH 8.7 n was determined to be 1.3. As the reason of these altered binding properties a blockade of the primary amino groups, disturbance of the salt bridges, and restrained cooperative mobility of the Hb-subunits are discussed. The Hill coefficient is additionally lowered by the heterogeneity of the immobilized Hb.", "contents": "[The effect of the immobilization of hemoglobin on its oxygen binding]. Hemoglobin (Hb) covalently fixed to CM-Sephadex was found to bind oxygen in weakly acidic medium with higher affinity than free Hb. The opposite relation is seen in the alkaline pH region. The alkaline Bohr effect was determined to be -0.2 only. Cooperativity is pH dependent. The sigmoid coefficient at pH 6 is 0.7; at pH 8.7 n was determined to be 1.3. As the reason of these altered binding properties a blockade of the primary amino groups, disturbance of the salt bridges, and restrained cooperative mobility of the Hb-subunits are discussed. The Hill coefficient is additionally lowered by the heterogeneity of the immobilized Hb."}
{"id": "PMID:242170", "title": "[Characterization of the effect of bradykinin on the smooth muscle with special reference to its latency].", "content": "The biological activity of bradykinin on the isolated guinea-pig ileum is evident after a defined period of time - its latency. The latency of a bradykinin induced contraction is not caused by the strong protonization of the polypeptide. Analogues with the same or diminished basicity have a shorter latency than bradykinin. The latency is increased at high hydrogen concentration in comparison with the physiological pH-value. But this phenomenon is also observed at angiotensin, eledoisin, acetylcholine, histamine and barium chloride. The latency is dependent upon the temperature. Exogenous calcium ions are without demonstrable influence on the bradykinin induced latency. The membrane potential is not changed during the latency. The results are discussed in connection with the drug-receptor interactions.", "contents": "[Characterization of the effect of bradykinin on the smooth muscle with special reference to its latency]. The biological activity of bradykinin on the isolated guinea-pig ileum is evident after a defined period of time - its latency. The latency of a bradykinin induced contraction is not caused by the strong protonization of the polypeptide. Analogues with the same or diminished basicity have a shorter latency than bradykinin. The latency is increased at high hydrogen concentration in comparison with the physiological pH-value. But this phenomenon is also observed at angiotensin, eledoisin, acetylcholine, histamine and barium chloride. The latency is dependent upon the temperature. Exogenous calcium ions are without demonstrable influence on the bradykinin induced latency. The membrane potential is not changed during the latency. The results are discussed in connection with the drug-receptor interactions."}
{"id": "PMID:242171", "title": "Alpha-N-benzoylarginine-2-naphthylamide hydrolase (cathepsin B1?) from rat skin. I. Preliminary experiments with skin extract.", "content": "The cathepsin B1-like, alpha-N-benzoyl-DL-arginine-2-naphthylamide (BANA) hydrolyzing activity of rat skin extract was studied. The enzyme was extracted into low ionic strength buffers, and was activated by dithiothreitol, EDTA and KCN. Incubation of the extract at acidic pH resulted in a 3.6-fold increase in its BANA hydrolase activity. The presence of inhibitor(s) of BANA hydrolase in the skin extract was indicated by the non-linearity of the activity/enzyme concentration curve and by Sephadex G-100 gel chromatography, which also caused separation of several other skin proteases.", "contents": "Alpha-N-benzoylarginine-2-naphthylamide hydrolase (cathepsin B1?) from rat skin. I. Preliminary experiments with skin extract. The cathepsin B1-like, alpha-N-benzoyl-DL-arginine-2-naphthylamide (BANA) hydrolyzing activity of rat skin extract was studied. The enzyme was extracted into low ionic strength buffers, and was activated by dithiothreitol, EDTA and KCN. Incubation of the extract at acidic pH resulted in a 3.6-fold increase in its BANA hydrolase activity. The presence of inhibitor(s) of BANA hydrolase in the skin extract was indicated by the non-linearity of the activity/enzyme concentration curve and by Sephadex G-100 gel chromatography, which also caused separation of several other skin proteases."}
{"id": "PMID:242172", "title": "Properties of the glycoprotein laccase immobilized by two methods.", "content": "Laccase (p-diphenol:oxygen oxidoreductase; EC 1.10.3.2) from Neurospora crassa has been immobilized by two different procedures: (1) Covalent attachment to Sepharose 4B activated with cyanogen bromide, and (2) Adsorption to Concanavalin A-Sepharose via the carbohydrate moiety. Except for small changes in the Michaelis-Menten constants, no differences were noted in the enzymological properties of the immobilized enzymes when compared to free enzyme. The carbohydrate moiety of laccase involved in the interaction with Concanavalin A does not appear to be closely associated with the active center since binding to the lectin has no effect on the enzymological parameters investigated.", "contents": "Properties of the glycoprotein laccase immobilized by two methods. Laccase (p-diphenol:oxygen oxidoreductase; EC 1.10.3.2) from Neurospora crassa has been immobilized by two different procedures: (1) Covalent attachment to Sepharose 4B activated with cyanogen bromide, and (2) Adsorption to Concanavalin A-Sepharose via the carbohydrate moiety. Except for small changes in the Michaelis-Menten constants, no differences were noted in the enzymological properties of the immobilized enzymes when compared to free enzyme. The carbohydrate moiety of laccase involved in the interaction with Concanavalin A does not appear to be closely associated with the active center since binding to the lectin has no effect on the enzymological parameters investigated."}
{"id": "PMID:242173", "title": "alpha-N-benzoylarginine-2-naphthylamide hydrolase (cathepsin B1 ?) from rat skin. II. Purification of the enzyme and demonstration of two inhibitors in the skin.", "content": "A thiol-activated, alpha-N-benzoylarginine-2-naph-thylamide (BANA) hydrolyzing enzyme was purified from rat skin by ammonium sulfate precipitation, gel filtration, and DEAE cellulose chromatography. In DEAE cellulose chromatography the enzyme was fractionated into two multiple forms (preparations I and II). The activity of undiluted preparation II, but not that of preparation I, was increased, when the enzyme was preincubated at pH 4, at 55 degrees C. Simultaneously, the isoelectric point of preparation II was shifted to that of preparation I, i.e., from 6.2 to 7.5. Activated preparation II behaved in DEAE cellulose chromatography as preparation I. Molecular weights of the enzymes of both preparations were 27 000, and pH optima were at pH 5.8 and 7.0, for BANA and leucine-2-napthylamide (Leu-NA), respectively. The BANA and Leu-NA hydrolyzing enzymes could not be separated by gel filtration, DEAE, CM, or Amberlite IRC-50 chromatography, isoelectric focusing, or analytical polyacrylamide gel electrophoresis. Two inhibitors of BANA hydrolase were demonstrated by gel filtration in the salt precipitated skin extract. The activities of the BANA hydrolase preparations did not increase linearly with increasing enzyme concentration, with the exceptions of activities of preparation I and acid-activated preparation II. The role of the inhibitors in the nonlinearity of the activity/enzyme concentration curves is discussed.", "contents": "alpha-N-benzoylarginine-2-naphthylamide hydrolase (cathepsin B1 ?) from rat skin. II. Purification of the enzyme and demonstration of two inhibitors in the skin. A thiol-activated, alpha-N-benzoylarginine-2-naph-thylamide (BANA) hydrolyzing enzyme was purified from rat skin by ammonium sulfate precipitation, gel filtration, and DEAE cellulose chromatography. In DEAE cellulose chromatography the enzyme was fractionated into two multiple forms (preparations I and II). The activity of undiluted preparation II, but not that of preparation I, was increased, when the enzyme was preincubated at pH 4, at 55 degrees C. Simultaneously, the isoelectric point of preparation II was shifted to that of preparation I, i.e., from 6.2 to 7.5. Activated preparation II behaved in DEAE cellulose chromatography as preparation I. Molecular weights of the enzymes of both preparations were 27 000, and pH optima were at pH 5.8 and 7.0, for BANA and leucine-2-napthylamide (Leu-NA), respectively. The BANA and Leu-NA hydrolyzing enzymes could not be separated by gel filtration, DEAE, CM, or Amberlite IRC-50 chromatography, isoelectric focusing, or analytical polyacrylamide gel electrophoresis. Two inhibitors of BANA hydrolase were demonstrated by gel filtration in the salt precipitated skin extract. The activities of the BANA hydrolase preparations did not increase linearly with increasing enzyme concentration, with the exceptions of activities of preparation I and acid-activated preparation II. The role of the inhibitors in the nonlinearity of the activity/enzyme concentration curves is discussed."}
{"id": "PMID:242175", "title": "The effect of artificial cryptorchidism on serum oestrogen and testosterone levels in the adult male rat.", "content": "Oestrone, oestradiol and testosterone levels were measured by radioimmunoassay in male rats 0.5, 1, 4, 8 and 16 days after rats were either made artifically cryptorchid or sham-operated. Oestradiol levels were not significantly different between cryptorchid and control rats 12 h or 1 day after surgery, but levels in cryptorchid animals fell to 35% of controls on day 4 (P less than 0.05), 31% on day 8, and 29% on day 16 (P less than 0.01). Conversely, oestrone and the total of the two oestrogens was higher in cryptorchid rats at one-half day (P less than 0.05), but did not differ at any other time. Testosterone levels were generally lower in cryptorchid rats than in controls. The minor contribution of oestradiol to total oestrogen levels and the lack of change of total oestrogens in cryptorchid rats led to the conclusion that oestrogens are probably not the tubular regulator of FSH in the male.", "contents": "The effect of artificial cryptorchidism on serum oestrogen and testosterone levels in the adult male rat. Oestrone, oestradiol and testosterone levels were measured by radioimmunoassay in male rats 0.5, 1, 4, 8 and 16 days after rats were either made artifically cryptorchid or sham-operated. Oestradiol levels were not significantly different between cryptorchid and control rats 12 h or 1 day after surgery, but levels in cryptorchid animals fell to 35% of controls on day 4 (P less than 0.05), 31% on day 8, and 29% on day 16 (P less than 0.01). Conversely, oestrone and the total of the two oestrogens was higher in cryptorchid rats at one-half day (P less than 0.05), but did not differ at any other time. Testosterone levels were generally lower in cryptorchid rats than in controls. The minor contribution of oestradiol to total oestrogen levels and the lack of change of total oestrogens in cryptorchid rats led to the conclusion that oestrogens are probably not the tubular regulator of FSH in the male."}
{"id": "PMID:242176", "title": "[Androgenic treatment with depot mesterolone in dyspermia].", "content": "The clinical use of testosterone, and more recently of orally administered mesterolone in disorders of male fertility is of limited therapeutic efficacy, as shown by data found in the literature. On the basis of these considerations, the authors have tested mesterolone cyclopentylproprionate in 15 subjects suffering from sperm disorders. The drug, which is slowly released in the tissues has been parenterally administered at a total dose of 1,200 mg (100 mg per week). During the therapeutic trial the following aspects have been studied: spermiologic and hormonal patterns, general conditions, libido, principal organic functions and the possible side effects. Results are critically evaluated.", "contents": "[Androgenic treatment with depot mesterolone in dyspermia]. The clinical use of testosterone, and more recently of orally administered mesterolone in disorders of male fertility is of limited therapeutic efficacy, as shown by data found in the literature. On the basis of these considerations, the authors have tested mesterolone cyclopentylproprionate in 15 subjects suffering from sperm disorders. The drug, which is slowly released in the tissues has been parenterally administered at a total dose of 1,200 mg (100 mg per week). During the therapeutic trial the following aspects have been studied: spermiologic and hormonal patterns, general conditions, libido, principal organic functions and the possible side effects. Results are critically evaluated."}
{"id": "PMID:242177", "title": "[Histochemical evidence of aminotransferases. III. Localization of aminotransferases in the mesencephalon, diencephalon, cortex cerebri and in the peripheral nervous system (author's transl)].", "content": "The histochemical distribution of some aminotransferases at various levels through the midbrain and cerebrum and in the peripheral nervous system of the rat has been described. The selective localization of the reaction product in the neurons and the neuropil was the same for the aminotransferases studied. There was a difference in the intensity of the enzyme activity. The white matter was negative, and only the glial cells and the blood vessels exhibit transaminase activity. Some nuclei showed an intensive reaction in the neurons and neuropil: nuel. ruber, substantia nigra, hypothalamic nuclei, Ammon's horn. A high activity was observed in the ganglion cell, and the nerve fibres were negative. There was a great similarity between the pattern of distribution for aminotransferases and that for some dehydrogenases.", "contents": "[Histochemical evidence of aminotransferases. III. Localization of aminotransferases in the mesencephalon, diencephalon, cortex cerebri and in the peripheral nervous system (author's transl)]. The histochemical distribution of some aminotransferases at various levels through the midbrain and cerebrum and in the peripheral nervous system of the rat has been described. The selective localization of the reaction product in the neurons and the neuropil was the same for the aminotransferases studied. There was a difference in the intensity of the enzyme activity. The white matter was negative, and only the glial cells and the blood vessels exhibit transaminase activity. Some nuclei showed an intensive reaction in the neurons and neuropil: nuel. ruber, substantia nigra, hypothalamic nuclei, Ammon's horn. A high activity was observed in the ganglion cell, and the nerve fibres were negative. There was a great similarity between the pattern of distribution for aminotransferases and that for some dehydrogenases."}
{"id": "PMID:242178", "title": "[Histochemical evidence of aminotransferases. IV. Histochemical and electrophoretical investigation of aminotransferases in rat organs (author's transl)].", "content": "The histochemical localization and isoenzyme profil of some aminotransferases in different organs of the rat has been studied. A positive histochemical reaction with unequal intensity, depending on the aminotransferase investigated, was been observed. The topochemical and cytochemical localization of the aminotransferases was typical for everyone organ. The studied aminotransferases possessed isoenzyme fractions with characteristic number, electrophoretic mobility and intensity in the different organs. The results were discussed in relation with substrate specifity of the aminotransferases.", "contents": "[Histochemical evidence of aminotransferases. IV. Histochemical and electrophoretical investigation of aminotransferases in rat organs (author's transl)]. The histochemical localization and isoenzyme profil of some aminotransferases in different organs of the rat has been studied. A positive histochemical reaction with unequal intensity, depending on the aminotransferase investigated, was been observed. The topochemical and cytochemical localization of the aminotransferases was typical for everyone organ. The studied aminotransferases possessed isoenzyme fractions with characteristic number, electrophoretic mobility and intensity in the different organs. The results were discussed in relation with substrate specifity of the aminotransferases."}
{"id": "PMID:242179", "title": "An optimum pH for the demonstration of chitin in Periplanata americana using Lugol's iodine.", "content": "Modification of chitosan test of Campbell is suggested with a controlled procedure involving heating with saturated potassium hydroxide at 160 degrees C for a period of 45 min and subsequent washing of the deacetylated chitin in running water and application of Lugol's iodine solution (1:2:300, w/w/v) at a pH range of 1.4 to 4.0, thus replacing the use of dilute sulphuric acid. Consistent results were obtained not only with the cuticle of Periplanata americana but also with the cuticle of Emerita asiatica (crustacea).", "contents": "An optimum pH for the demonstration of chitin in Periplanata americana using Lugol's iodine. Modification of chitosan test of Campbell is suggested with a controlled procedure involving heating with saturated potassium hydroxide at 160 degrees C for a period of 45 min and subsequent washing of the deacetylated chitin in running water and application of Lugol's iodine solution (1:2:300, w/w/v) at a pH range of 1.4 to 4.0, thus replacing the use of dilute sulphuric acid. Consistent results were obtained not only with the cuticle of Periplanata americana but also with the cuticle of Emerita asiatica (crustacea)."}
{"id": "PMID:242180", "title": "Serum cholinesterase activity in burned patients. II: anaesthesia, suxamethonium and hyperkalaemia.", "content": "The importance of serum cholinesterase activity in burned patients was evaluated in relation to anaesthesia. Anaesthesia included a repeated administration of suxamethonium. Thirty-two patients with an estimated area of burn between 3 and 72% were studied during 39 anaesthetic procedures. A statistically significant inverse correlation was found between serum cholinesterase activity and the apnoea period following intravenous suxamethonium. In patients with very low enzyme activity, apnoea periods of 10 to 25 min were observed. No correlation was found between the changes in serum potassium following suxamethonium and either the serum cholinesterase activity or the changes in Pco2 and pH. The most reliable parameters in predicting a dangerous increase in serum potassium following intravenous suxamethonium were shown to be 1) the time elapsed from burn injury to anesthesia and 2) the degree of burn injury. However, abnormal reactions to suxamethonium were seen as early as 9 days following injury, and rises in serum potassium to over 6 mmol/l were observed even in patients with a total burn surface of around 8%, i.e., less than the surface of one arm.", "contents": "Serum cholinesterase activity in burned patients. II: anaesthesia, suxamethonium and hyperkalaemia. The importance of serum cholinesterase activity in burned patients was evaluated in relation to anaesthesia. Anaesthesia included a repeated administration of suxamethonium. Thirty-two patients with an estimated area of burn between 3 and 72% were studied during 39 anaesthetic procedures. A statistically significant inverse correlation was found between serum cholinesterase activity and the apnoea period following intravenous suxamethonium. In patients with very low enzyme activity, apnoea periods of 10 to 25 min were observed. No correlation was found between the changes in serum potassium following suxamethonium and either the serum cholinesterase activity or the changes in Pco2 and pH. The most reliable parameters in predicting a dangerous increase in serum potassium following intravenous suxamethonium were shown to be 1) the time elapsed from burn injury to anesthesia and 2) the degree of burn injury. However, abnormal reactions to suxamethonium were seen as early as 9 days following injury, and rises in serum potassium to over 6 mmol/l were observed even in patients with a total burn surface of around 8%, i.e., less than the surface of one arm."}
{"id": "PMID:242181", "title": "Anesthesia for cesarean section II: effects of the induction-delivery interval on the respiratory adaptation of the newborn in elective cesarean section.", "content": "Ten healthy mothers and their infants were studied in connection with elective cesarean section. Anesthesia was induced with 250-300 mg hexobarbitone followed by 100 mg succinylcholine for endotracheal intubation. The surgeon started the operation when the eyelid reflex disappeared, and delivered the baby as quickly as possible. Mean induction-delivery (I-D) interval was 2 min 45 s. Anesthesia was then deepened with further barbiturate, diazepam and methoxyflurane, and alcuronium used as muscle relaxant. The respiratory adaptation of the infant was studied by blood gas and acid-base measurements in repeated arterial samples during the first three hours of life. The mothers were interviewed after 3-12 months. A comparison was made with another barbiturate group with a longer I-D interval (x = 9 min 10 s). The present material showed initially higher PaO2 lower PaCO2, higher pH and less base deficit (BD), which relfected the maternal state at delivery. After 10-30 min, the results approached equivalence, though the babies in the short I-D group showed a tendency toward normalization of metabolic acidosis earlier. At the interviews, two mothers complained of pain during skin incision, and two of nightmares. Anesthesia with barbiturate for cesarean section with the I-D intervals studied in both groups allowed good respiratory adaptation in the infants. There is, neverless, the need for an adequate period of time between induction and the start of the operation in order to minimize the risk for maternal awareness.", "contents": "Anesthesia for cesarean section II: effects of the induction-delivery interval on the respiratory adaptation of the newborn in elective cesarean section. Ten healthy mothers and their infants were studied in connection with elective cesarean section. Anesthesia was induced with 250-300 mg hexobarbitone followed by 100 mg succinylcholine for endotracheal intubation. The surgeon started the operation when the eyelid reflex disappeared, and delivered the baby as quickly as possible. Mean induction-delivery (I-D) interval was 2 min 45 s. Anesthesia was then deepened with further barbiturate, diazepam and methoxyflurane, and alcuronium used as muscle relaxant. The respiratory adaptation of the infant was studied by blood gas and acid-base measurements in repeated arterial samples during the first three hours of life. The mothers were interviewed after 3-12 months. A comparison was made with another barbiturate group with a longer I-D interval (x = 9 min 10 s). The present material showed initially higher PaO2 lower PaCO2, higher pH and less base deficit (BD), which relfected the maternal state at delivery. After 10-30 min, the results approached equivalence, though the babies in the short I-D group showed a tendency toward normalization of metabolic acidosis earlier. At the interviews, two mothers complained of pain during skin incision, and two of nightmares. Anesthesia with barbiturate for cesarean section with the I-D intervals studied in both groups allowed good respiratory adaptation in the infants. There is, neverless, the need for an adequate period of time between induction and the start of the operation in order to minimize the risk for maternal awareness."}
{"id": "PMID:242182", "title": "Continuous measurement of arterial PO2, PCO2 and pH during autotransplantation of canine hearts.", "content": "Arterial PO2, PCO2 and pH were measured continuously with electrodes placed in a flow cuvette. Comparison between continuous readings and results of single sample analyses showed practically no discrepancy, and the drifts of the electrodes during time of measurements were negligible. During hypothermic perfusion with a Rygg-Kyvsg\u00e5rd bubble oxygenator, autotransplantation of canine hearts was performed. PO2, PCO2 and pH were measured continuously to check the performance of the heart-lung machine, and to evaluate the therapeutic and diagnostic significance of these blood gas values during cardiac surgery. At the start of perfusion, a steep fall in all three parameters was observed. The average fall in PO2 was 313 mmHg; PCO2 fell by 15 mmHg and pH BY 0.15. PCO2 rapidly returned to normal values, while pH and PO2 increased slowly during the perfusion period. PO2 reached its highest value at the lowest temperature and fell during rewarming. PCO was regulated by the carbon dioxide concentration in the heart-lung machine. pH did not return to normal levels within the time of perfusion. In the transistional period from perfusion, PCO2 increased and pH fell. Alterations in the distribution and direction of blood flow and a low systemic blood pressure are possible explanations of the initial fall in PO2 and the post-perfusion changes in PCO2 and pH. The variations in pH and PCO2 at the start of perfusion were caused by an acid priming fluid with low CO2 content. The post-perfusion changes indicated an unstable circulation, but imminent myocardial failure could not alone be diagnosed by continuous measurement.", "contents": "Continuous measurement of arterial PO2, PCO2 and pH during autotransplantation of canine hearts. Arterial PO2, PCO2 and pH were measured continuously with electrodes placed in a flow cuvette. Comparison between continuous readings and results of single sample analyses showed practically no discrepancy, and the drifts of the electrodes during time of measurements were negligible. During hypothermic perfusion with a Rygg-Kyvsg\u00e5rd bubble oxygenator, autotransplantation of canine hearts was performed. PO2, PCO2 and pH were measured continuously to check the performance of the heart-lung machine, and to evaluate the therapeutic and diagnostic significance of these blood gas values during cardiac surgery. At the start of perfusion, a steep fall in all three parameters was observed. The average fall in PO2 was 313 mmHg; PCO2 fell by 15 mmHg and pH BY 0.15. PCO2 rapidly returned to normal values, while pH and PO2 increased slowly during the perfusion period. PO2 reached its highest value at the lowest temperature and fell during rewarming. PCO was regulated by the carbon dioxide concentration in the heart-lung machine. pH did not return to normal levels within the time of perfusion. In the transistional period from perfusion, PCO2 increased and pH fell. Alterations in the distribution and direction of blood flow and a low systemic blood pressure are possible explanations of the initial fall in PO2 and the post-perfusion changes in PCO2 and pH. The variations in pH and PCO2 at the start of perfusion were caused by an acid priming fluid with low CO2 content. The post-perfusion changes indicated an unstable circulation, but imminent myocardial failure could not alone be diagnosed by continuous measurement."}
{"id": "PMID:242183", "title": "Phosphatases in the lingual glands of man and dog.", "content": "Phosphatase activity was demonstrated in the lingual glands of man and dog. Especially the ducts of the glandular elements of the dog exhibited a peculiar and rather perplexing pattern of activity which does not seem to fit in with any of the prevailing concepts of the function of the duct system. The secretory capillaries (Sekretionscapillaren) in many of the serous acini of the human lingual glands have demonstrated phosphatase activity with all the 17 substrates used. The significance of these phosphatases, expecially ATPase, in the active transport across biological unit membranes has been discussed.", "contents": "Phosphatases in the lingual glands of man and dog. Phosphatase activity was demonstrated in the lingual glands of man and dog. Especially the ducts of the glandular elements of the dog exhibited a peculiar and rather perplexing pattern of activity which does not seem to fit in with any of the prevailing concepts of the function of the duct system. The secretory capillaries (Sekretionscapillaren) in many of the serous acini of the human lingual glands have demonstrated phosphatase activity with all the 17 substrates used. The significance of these phosphatases, expecially ATPase, in the active transport across biological unit membranes has been discussed."}
{"id": "PMID:242184", "title": "The use of sulthiame- in myoclonic epilepsy of childhood and adolescence.", "content": "Sulthiame has been used by most investigators in psychomotor seizures, other focal seizures and grand-mal, usually in conjuction with other anticonvulsants. Reports on its use in myoclonic epilepsy and as a sole anti-convulsant are few and inconclusive. The present report presents the results of a study carried out on the use of sulthiame in 54 cases of myoclonic epilepsies originating in infancy, childhood and adolescence. The different types of myoclonic epilepsy are defined. An illustrative case report is included. Results indicated that sulthiame is the drug of choice, often as the sole anti-convulsive agent, in cases of \"juvenile myoclonic epilepsy\". In the myoclonic encephalopathies of childhood (the so-called \"minor motor epilepsy\" or Lennox-Gastaut syndrome), which are notoriously refractory to therapy, sulthiame appears to be an efficacious adjunct to currently-used agents, including benzodiazepines, succinimides, dipropyl acetate, steriods and a ketogenic diet.", "contents": "The use of sulthiame- in myoclonic epilepsy of childhood and adolescence. Sulthiame has been used by most investigators in psychomotor seizures, other focal seizures and grand-mal, usually in conjuction with other anticonvulsants. Reports on its use in myoclonic epilepsy and as a sole anti-convulsant are few and inconclusive. The present report presents the results of a study carried out on the use of sulthiame in 54 cases of myoclonic epilepsies originating in infancy, childhood and adolescence. The different types of myoclonic epilepsy are defined. An illustrative case report is included. Results indicated that sulthiame is the drug of choice, often as the sole anti-convulsive agent, in cases of \"juvenile myoclonic epilepsy\". In the myoclonic encephalopathies of childhood (the so-called \"minor motor epilepsy\" or Lennox-Gastaut syndrome), which are notoriously refractory to therapy, sulthiame appears to be an efficacious adjunct to currently-used agents, including benzodiazepines, succinimides, dipropyl acetate, steriods and a ketogenic diet."}
{"id": "PMID:242185", "title": "Bilateral keratopathy and tyrosinosis.", "content": "A case of tyrosinosis due to lack of soluble tyrosine aminotransferase is described. The first clinical sign of this disorder may be bilateral keratopathy. Treatment is diet with restriction of phenylalanine and tyrosine. The disorder is rare and must be differentiated from other conditions of tyrosinosis.", "contents": "Bilateral keratopathy and tyrosinosis. A case of tyrosinosis due to lack of soluble tyrosine aminotransferase is described. The first clinical sign of this disorder may be bilateral keratopathy. Treatment is diet with restriction of phenylalanine and tyrosine. The disorder is rare and must be differentiated from other conditions of tyrosinosis."}
{"id": "PMID:242186", "title": "Survival after massive pulmonary haemorrhage in the neonatal period.", "content": "4 babies with massive pulmonary haemorrhage were seen in an 18 month period. 2 had severe rhesus maemolytic disease, and the other 2 severe respiratory problems. There was evidence of a profound respiratory acidosis and hypoxia prior to the onset of the haemorrhage. 2 babies survived the episode and subsequently developed normally. Adequate ventilation and attendance to the treatment of blood coagulation disorders may have been a factor in their survival.", "contents": "Survival after massive pulmonary haemorrhage in the neonatal period. 4 babies with massive pulmonary haemorrhage were seen in an 18 month period. 2 had severe rhesus maemolytic disease, and the other 2 severe respiratory problems. There was evidence of a profound respiratory acidosis and hypoxia prior to the onset of the haemorrhage. 2 babies survived the episode and subsequently developed normally. Adequate ventilation and attendance to the treatment of blood coagulation disorders may have been a factor in their survival."}
{"id": "PMID:242187", "title": "Metabolic characteristics of fibre types in human skeletal muscle.", "content": "Muscle biopsy samples were obtained from healthy subjects in order to evaluate quantitative differences in single fibres of substrate (glycogen and triglyceride) and ion concentrations (Na+ and K+) as well as enzyme activity levels (succinate-dehydrogenase, SDH; phosphofructokinase, PFK; 3-hydroxyacyl-CoA-dehydrogenase, HAD; myosin ATPase) between human skeletal muscle fibre types. After freeze drying of the muscle specimen fragments of single fibres were dissected out and stained for myofibrillar-ATPase with preincubations at pH's of 10.3, 4.6, 4.35. Type I (\"red\") and II A,B, and C (\"white\") fibres could then be identified. Glycogen content was the same in different fibres, whereas triglyceride content was highest in Type I fibres (2-3 X Type II). No significant differences were observed for Na+ and K+ between fibre types. The activity for the enzymes studied were quite different in the fibre types (SDH and HAD, Type I is approximately 1.5 X Type II; PFK Type I is approximately 0.5 X Type II, Myosin ATPase Type I is approxiamtely 0.4 X Type II). The subgroups of Type II fibres were distinguished by differences in both SDH and PFK activities (SDH, Type II C is greater than A is greater than B; PFK, Type II B is greater than A is approximately C). It is concluded that contractile and metabolic characteristics of human skeletal fibres are very similar to many other species. One difference, however, appears to be than no Type II fibres have an oxidative potential higher than Type I fibres.", "contents": "Metabolic characteristics of fibre types in human skeletal muscle. Muscle biopsy samples were obtained from healthy subjects in order to evaluate quantitative differences in single fibres of substrate (glycogen and triglyceride) and ion concentrations (Na+ and K+) as well as enzyme activity levels (succinate-dehydrogenase, SDH; phosphofructokinase, PFK; 3-hydroxyacyl-CoA-dehydrogenase, HAD; myosin ATPase) between human skeletal muscle fibre types. After freeze drying of the muscle specimen fragments of single fibres were dissected out and stained for myofibrillar-ATPase with preincubations at pH's of 10.3, 4.6, 4.35. Type I (\"red\") and II A,B, and C (\"white\") fibres could then be identified. Glycogen content was the same in different fibres, whereas triglyceride content was highest in Type I fibres (2-3 X Type II). No significant differences were observed for Na+ and K+ between fibre types. The activity for the enzymes studied were quite different in the fibre types (SDH and HAD, Type I is approximately 1.5 X Type II; PFK Type I is approximately 0.5 X Type II, Myosin ATPase Type I is approxiamtely 0.4 X Type II). The subgroups of Type II fibres were distinguished by differences in both SDH and PFK activities (SDH, Type II C is greater than A is greater than B; PFK, Type II B is greater than A is approximately C). It is concluded that contractile and metabolic characteristics of human skeletal fibres are very similar to many other species. One difference, however, appears to be than no Type II fibres have an oxidative potential higher than Type I fibres."}
{"id": "PMID:242188", "title": "Inhibition of induced pinocytosis in Amoeba proteus by membrane stabilizing drugs.", "content": "The effect of membrane stabilizing drugs on cation induced pinocytosis was studied in Amoeba proteus. Initially the presence of local anesthetic drugs during a pinocytosis cycle had a stimulating effect on channel formation, however, the capacity to develop pinocytotic channels was reversibly inhibited after a period of treatment with these drugs. Imipramine, vinblastine and the phenothiazines had effects similar to local anaesthetics. The local anesthetics inhibited pinocytosis in the following order: dibucaine greater than tetracaine greater than bupivacaine greater than lidocaine greater than procaine, and the phenothiazines: thioridazine greater than prochlorperazine greater chlorpromazine greater than prometazine. Pinocytosis, when induced by Na+ or tris, was more affected by the drugs and by calcium binding agents than pinocytosis induced by K+. After pretreatment with inhibitory concentration of dibucaine (3 x 10(-4) M) the depolarization of the membrane and the conductance increase during pinocytosis were normal, while the increase of oxygen uptake during the pincoytosis cycle was abolished. Addition of Ca++ before, during or after dibucaine treatment decreased the effect of the drug. Conversely, in dibucaine-treated cells, cation induced pinocytosis was less inhibited by Ca++ than pinocytosis in normal cells. Addition of EGTA to the inducing solutions potentiated the inhibitory effect of the drug. It is suggested that these drugs release Ca++ from the cell surface and at higher concentration or after prolonged incubation time interfere with a Ca++ mechanism which couples the membrane and contractile systems in the cytoplasm.", "contents": "Inhibition of induced pinocytosis in Amoeba proteus by membrane stabilizing drugs. The effect of membrane stabilizing drugs on cation induced pinocytosis was studied in Amoeba proteus. Initially the presence of local anesthetic drugs during a pinocytosis cycle had a stimulating effect on channel formation, however, the capacity to develop pinocytotic channels was reversibly inhibited after a period of treatment with these drugs. Imipramine, vinblastine and the phenothiazines had effects similar to local anaesthetics. The local anesthetics inhibited pinocytosis in the following order: dibucaine greater than tetracaine greater than bupivacaine greater than lidocaine greater than procaine, and the phenothiazines: thioridazine greater than prochlorperazine greater chlorpromazine greater than prometazine. Pinocytosis, when induced by Na+ or tris, was more affected by the drugs and by calcium binding agents than pinocytosis induced by K+. After pretreatment with inhibitory concentration of dibucaine (3 x 10(-4) M) the depolarization of the membrane and the conductance increase during pinocytosis were normal, while the increase of oxygen uptake during the pincoytosis cycle was abolished. Addition of Ca++ before, during or after dibucaine treatment decreased the effect of the drug. Conversely, in dibucaine-treated cells, cation induced pinocytosis was less inhibited by Ca++ than pinocytosis in normal cells. Addition of EGTA to the inducing solutions potentiated the inhibitory effect of the drug. It is suggested that these drugs release Ca++ from the cell surface and at higher concentration or after prolonged incubation time interfere with a Ca++ mechanism which couples the membrane and contractile systems in the cytoplasm."}
{"id": "PMID:242189", "title": "L-asparaginase activity of Mycobacterium phlei under various growth conditions.", "content": "Seven Mycobacterium strains were grown statically on salts-glycerol-asparagine (Sauton) or on salts-glucose-glutamate (Sym) media. At desired time of incubation, the bacteria were washed with water, disintegrated with powdered corundum and in resulting cell-free extracts L-asparaginase activity was determined by the Conway method. The majority of experiments were performed on M. phlei which exhibited considerable rise in L-asparaginase activity with increasing age of the culture. This change did not occur on Sym medium because of Zn2+, which proved to abolish the effect of the enzyme induction in vivo but did not inhibit the activity in vitro. Addition of rifampicin to Sauton culture media resulted in a low enzyme level. Exogenous asparagine and glycerol were not indispensable for the enzyme synthesis and could be replaced by glutamate and glucose, respectively.", "contents": "L-asparaginase activity of Mycobacterium phlei under various growth conditions. Seven Mycobacterium strains were grown statically on salts-glycerol-asparagine (Sauton) or on salts-glucose-glutamate (Sym) media. At desired time of incubation, the bacteria were washed with water, disintegrated with powdered corundum and in resulting cell-free extracts L-asparaginase activity was determined by the Conway method. The majority of experiments were performed on M. phlei which exhibited considerable rise in L-asparaginase activity with increasing age of the culture. This change did not occur on Sym medium because of Zn2+, which proved to abolish the effect of the enzyme induction in vivo but did not inhibit the activity in vitro. Addition of rifampicin to Sauton culture media resulted in a low enzyme level. Exogenous asparagine and glycerol were not indispensable for the enzyme synthesis and could be replaced by glutamate and glucose, respectively."}
{"id": "PMID:242190", "title": "The effect of microorganisms on phytotoxicity of herbicides. III. Interaction of Bacillus sp. 72 with Venzar.", "content": "Interactions between Venzar and some metabolites of Bacillus ps. 72 were studied. This strain was found to produce flavonoids increasing the phytotoxicity of Venzar. Venzar action was also increased by NH4+ ions released aboundantly by the bacterial strain.", "contents": "The effect of microorganisms on phytotoxicity of herbicides. III. Interaction of Bacillus sp. 72 with Venzar. Interactions between Venzar and some metabolites of Bacillus ps. 72 were studied. This strain was found to produce flavonoids increasing the phytotoxicity of Venzar. Venzar action was also increased by NH4+ ions released aboundantly by the bacterial strain."}
{"id": "PMID:242191", "title": "Influence of amino acids on the activity of cellulolytic enzymes obtained from spent medium of Fusarium cultures and on the \"Cellulase S\" Novo.", "content": "Comparative studies on the influence of 4 amino acids (cysteine, cystine, methionine and alanine) on the activity of enzymatic preparation were carried out. The action of the amino acids was shown to depend on pH, incubation time and the temperature of incubation. Attempts were made to find a correlation between the amino acids introduced and redox potential (Eh), pH and the activity of the cellulolytic enzymes. It was found that the addition of some amino acids to the reaction mixtures at different pH values affected the value of Eh -- which enhanced the cellulase activity.", "contents": "Influence of amino acids on the activity of cellulolytic enzymes obtained from spent medium of Fusarium cultures and on the \"Cellulase S\" Novo. Comparative studies on the influence of 4 amino acids (cysteine, cystine, methionine and alanine) on the activity of enzymatic preparation were carried out. The action of the amino acids was shown to depend on pH, incubation time and the temperature of incubation. Attempts were made to find a correlation between the amino acids introduced and redox potential (Eh), pH and the activity of the cellulolytic enzymes. It was found that the addition of some amino acids to the reaction mixtures at different pH values affected the value of Eh -- which enhanced the cellulase activity."}
{"id": "PMID:242196", "title": "Behavioral analysis of the effects and mechanisms of action of benzodiazepines.", "content": "Conflict behavior is a powerful tool to reveal relevant pharmacologic correlates of the therapeutically desirable properties of benzodiazepine antianxiety compounds. The predictability of its clinical effectiveness in psychoneuroses is very high, and important quantitative and qualitative differences between compounds in this chemical class can be shown using such a behavioral technique. It is important to take these differences into account when studying biochemical correlates or mechanisms of action within the benzodiazepine class. Conflict behavior has been used to evaluate several biochemical hypotheses concerning the mechanism of action for the antianxiety properties of benzodiazepines. These studies found that inhibition of cyclic AMP phosphodiesterase did not seem to be a relevant factor. Similarly, experiments with AOAA did not provide evidence to support the involvement of GABA with benzodiazepines' antianxiety properties, nor did glycine receptor affinities correlate significantly with anticonflict effects. Thus, while it is reasonable at present to associate either GABA or glycine with the muscle-relaxant or anticonvulsant properties of benzodiazepines, no support was provided in the conflict procedure for their involvement in the anxiolytic effects. Partial support was provided for the proposal that serotonin is involved in the benzodiazepines' anxiolytic activity. This was determined in studies with the serotonin antagonists cinanserin and methysergide, which had anti-conflict activity, as well as in studies of monoamine turnover after initial chlordiazepoxide treatments to previously undrugged, conflict-trained rats.", "contents": "Behavioral analysis of the effects and mechanisms of action of benzodiazepines. Conflict behavior is a powerful tool to reveal relevant pharmacologic correlates of the therapeutically desirable properties of benzodiazepine antianxiety compounds. The predictability of its clinical effectiveness in psychoneuroses is very high, and important quantitative and qualitative differences between compounds in this chemical class can be shown using such a behavioral technique. It is important to take these differences into account when studying biochemical correlates or mechanisms of action within the benzodiazepine class. Conflict behavior has been used to evaluate several biochemical hypotheses concerning the mechanism of action for the antianxiety properties of benzodiazepines. These studies found that inhibition of cyclic AMP phosphodiesterase did not seem to be a relevant factor. Similarly, experiments with AOAA did not provide evidence to support the involvement of GABA with benzodiazepines' antianxiety properties, nor did glycine receptor affinities correlate significantly with anticonflict effects. Thus, while it is reasonable at present to associate either GABA or glycine with the muscle-relaxant or anticonvulsant properties of benzodiazepines, no support was provided in the conflict procedure for their involvement in the anxiolytic effects. Partial support was provided for the proposal that serotonin is involved in the benzodiazepines' anxiolytic activity. This was determined in studies with the serotonin antagonists cinanserin and methysergide, which had anti-conflict activity, as well as in studies of monoamine turnover after initial chlordiazepoxide treatments to previously undrugged, conflict-trained rats."}
{"id": "PMID:242199", "title": "Possible involvement of GABA in the central actions of benzodiazepines.", "content": "The effects of several benzodiazepines on a variety of nervous activities known or presumed to depend on GABA are presented and compared with those of agents that deplete or increase the level of endogenous GABA: antagonism of various convulsant agents in mice, enhancement of presynaptic inhibition in the spinal cord and the cuneate nucleus of cats, decrease of the spontaneous firing rate of cerebellar Purkinje cells in cats and rats, antagonism of bicuculine-induced depression of the strio-nigral-evoked potential in the cat, potentiation of haloperidol-induced catalepsy in rats, GABA-mimetic actions on drug-induced PGO-waves in cats and on eserine-induced circling in guinea pigs. Diazepam slightly increased the GABA level in the cat spinal cord and in the total brain of mice and rats; this increase does not seem to be due to an increase of GABA synthesis. It is concluded that benzodiazepines probably enhance presynaptic inhibition at all levels of the neuraxis and that this effect requires not only the presence of GABA but is also dependent on an activity of GABA-ergic neurons. Benzodiazepines also appear to enhance postsynaptic inhibition where this is mediated by GABA. Many actions of benzodiazepines can be tentatively explained by a stimulus-bound enhancement of GABA effects.", "contents": "Possible involvement of GABA in the central actions of benzodiazepines. The effects of several benzodiazepines on a variety of nervous activities known or presumed to depend on GABA are presented and compared with those of agents that deplete or increase the level of endogenous GABA: antagonism of various convulsant agents in mice, enhancement of presynaptic inhibition in the spinal cord and the cuneate nucleus of cats, decrease of the spontaneous firing rate of cerebellar Purkinje cells in cats and rats, antagonism of bicuculine-induced depression of the strio-nigral-evoked potential in the cat, potentiation of haloperidol-induced catalepsy in rats, GABA-mimetic actions on drug-induced PGO-waves in cats and on eserine-induced circling in guinea pigs. Diazepam slightly increased the GABA level in the cat spinal cord and in the total brain of mice and rats; this increase does not seem to be due to an increase of GABA synthesis. It is concluded that benzodiazepines probably enhance presynaptic inhibition at all levels of the neuraxis and that this effect requires not only the presence of GABA but is also dependent on an activity of GABA-ergic neurons. Benzodiazepines also appear to enhance postsynaptic inhibition where this is mediated by GABA. Many actions of benzodiazepines can be tentatively explained by a stimulus-bound enhancement of GABA effects."}
{"id": "PMID:242200", "title": "Modulators of cyclic AMP systems.", "content": "On the basis of the data reported here, one may conclude that although many agents that act in the central nervous system are modulators of the action of cyclic AMP, it is difficult to establish a direct connection between the pharmacologic activity and the levels of cyclic AMP in the brain. This lack of interrelation applies to the benzodiazepines as well as to the pyrazolopyridines. The data for members of the latter group are somewhat frustrating in this regard, since an excellent correlation has been shown to exist between the potency of inhibition of PDE and activity in the antianxiety test. In measurements of steroidogenesis in the isolated adrenal cell, the correlation between activity in vito and the conflict assay is even better. The data presented here and reported elsewhere (Shimizu et al., 1974; Kelly et al., 1974; Mayer and King, 1974; King and Mayer, 1974) provide evidence that agents that act as inhibitors of PDE in cell-free systems exert their influence on cyclic AMP in tissue slices of the brain of guinea pigs by mechanisms that seem not to be related to an effect on PDE. Papaverine, and possibly chlordiazepoxide, may act by releasing agonists that, in turn, stimulate the accumulation of cyclic AMP. This activity is blocked bo other inhibitors of PDE, such as theophyline. Results obtained by the use of platelets are refreshingly clear. Inhibition of aggregation has been shown to occur when the level of cyclic AMP is raised, and a suggestive exists that the most potent inhibitors of platelet PDE are the best potentiators of the action of PGE1 in blocking aggregation. The study utilizing drugs collected from a large number of therapeutic classes makes clear that it is difficult to attribute the mechanism of action for any of the classes studied to modulation of cyclic AMP. An unexpected finding of this study, however, was the fact that pharmacologic agents include an unusually large number of inhibitors of PDE as compared with agents chosen at random. This finding provides a powerful tool for the biochemical pharmacologist who is examining large numbers of compounds in the search for potential drugs.", "contents": "Modulators of cyclic AMP systems. On the basis of the data reported here, one may conclude that although many agents that act in the central nervous system are modulators of the action of cyclic AMP, it is difficult to establish a direct connection between the pharmacologic activity and the levels of cyclic AMP in the brain. This lack of interrelation applies to the benzodiazepines as well as to the pyrazolopyridines. The data for members of the latter group are somewhat frustrating in this regard, since an excellent correlation has been shown to exist between the potency of inhibition of PDE and activity in the antianxiety test. In measurements of steroidogenesis in the isolated adrenal cell, the correlation between activity in vito and the conflict assay is even better. The data presented here and reported elsewhere (Shimizu et al., 1974; Kelly et al., 1974; Mayer and King, 1974; King and Mayer, 1974) provide evidence that agents that act as inhibitors of PDE in cell-free systems exert their influence on cyclic AMP in tissue slices of the brain of guinea pigs by mechanisms that seem not to be related to an effect on PDE. Papaverine, and possibly chlordiazepoxide, may act by releasing agonists that, in turn, stimulate the accumulation of cyclic AMP. This activity is blocked bo other inhibitors of PDE, such as theophyline. Results obtained by the use of platelets are refreshingly clear. Inhibition of aggregation has been shown to occur when the level of cyclic AMP is raised, and a suggestive exists that the most potent inhibitors of platelet PDE are the best potentiators of the action of PGE1 in blocking aggregation. The study utilizing drugs collected from a large number of therapeutic classes makes clear that it is difficult to attribute the mechanism of action for any of the classes studied to modulation of cyclic AMP. An unexpected finding of this study, however, was the fact that pharmacologic agents include an unusually large number of inhibitors of PDE as compared with agents chosen at random. This finding provides a powerful tool for the biochemical pharmacologist who is examining large numbers of compounds in the search for potential drugs."}
{"id": "PMID:242201", "title": "Effects of benzodiazepines on central serotonergic mechanisms.", "content": "If the rat conflict test were a valid animal model of anxiety neurosis, evidence which implicates serotonin systems in the anxiety-reducing actions of benzodiazepine tranquilizers could be summarized as follows: (1) The punishment-lessening effects of benzodiazepines in the conflict test are mimicked by serotonin antagonists (methysergide, cinanserin, bromolysergic acid), serotonin synthesis inhibition (PCPA), and serotonin nerve terminal damage (5,6-dihydroxytryptamine). (2) Punishment effects may be intensified by the serotonin precursor, 5-hydroxytryptophan (in combination with a monoamine oxidase inhibitor), serotonin agonists (alpha-methyltryptamine), or intraventricular injections of serotonin itself. Intraventricularly administered serotonin also antagonizes the punishment-lessening effects of benzodiazepines. (3) Stimulation of the serotonergic cell bodies in the dorsal raphe nucleus by local application of crystalline carbachol causes intense suppression of behavior. The suppressive effects of raphe stimulation are antagonized by systemic administration of benzodiazepines. (4) In biochemical experiments, the decrease in norepinephrine turnover induced by oxazepam rapidly undergoes tolerance, whereas the decrease induced in serotonin turnover is maintained over repeated doses. These results parallel findings in the conflict test which indicate that the depressant action of oxazepam rapidly undergoes tolerance, whereas the anxiety-reducing action is maintained over repeated doses. Although central serotonin neurons are thus implicated in the therapeutic actions of benzodiazepine tranquilizers, it is quite possible that the drugs actually act indirectly to reduce serotonin activity. The concept that benzodiazepines may exert a primary action on GABA-containing neurons, which in turn regulate serotonergic transmission, was supported by preliminary psychopharmacological evidence. The GABA-antagonist picrotoxin, at doses that do not disrupt unpunished behavior, fully antagonizes the punishment-lessening effects of benzodiazepines in the conflict test.", "contents": "Effects of benzodiazepines on central serotonergic mechanisms. If the rat conflict test were a valid animal model of anxiety neurosis, evidence which implicates serotonin systems in the anxiety-reducing actions of benzodiazepine tranquilizers could be summarized as follows: (1) The punishment-lessening effects of benzodiazepines in the conflict test are mimicked by serotonin antagonists (methysergide, cinanserin, bromolysergic acid), serotonin synthesis inhibition (PCPA), and serotonin nerve terminal damage (5,6-dihydroxytryptamine). (2) Punishment effects may be intensified by the serotonin precursor, 5-hydroxytryptophan (in combination with a monoamine oxidase inhibitor), serotonin agonists (alpha-methyltryptamine), or intraventricular injections of serotonin itself. Intraventricularly administered serotonin also antagonizes the punishment-lessening effects of benzodiazepines. (3) Stimulation of the serotonergic cell bodies in the dorsal raphe nucleus by local application of crystalline carbachol causes intense suppression of behavior. The suppressive effects of raphe stimulation are antagonized by systemic administration of benzodiazepines. (4) In biochemical experiments, the decrease in norepinephrine turnover induced by oxazepam rapidly undergoes tolerance, whereas the decrease induced in serotonin turnover is maintained over repeated doses. These results parallel findings in the conflict test which indicate that the depressant action of oxazepam rapidly undergoes tolerance, whereas the anxiety-reducing action is maintained over repeated doses. Although central serotonin neurons are thus implicated in the therapeutic actions of benzodiazepine tranquilizers, it is quite possible that the drugs actually act indirectly to reduce serotonin activity. The concept that benzodiazepines may exert a primary action on GABA-containing neurons, which in turn regulate serotonergic transmission, was supported by preliminary psychopharmacological evidence. The GABA-antagonist picrotoxin, at doses that do not disrupt unpunished behavior, fully antagonizes the punishment-lessening effects of benzodiazepines in the conflict test."}
{"id": "PMID:242202", "title": "The possible involvement of GABA mechanisms in the action of benzodiazepines on central catecholamine neurons.", "content": "With the use of quantitative microspectrofluorometry, it has been shown that diazepam (10 mg/kg) and chlordiazepoxide (10 mg/kg) reduce DA turnover in the tuberculum olfactorium, nuc. accumbens, the DA islands of the entorhinal cortex, and caput of nuc. caudatus, whereas DA turnover is increased in the lateral external layer of the median eminence after 10 mg/kg of diazepam. It is of considerable interest that with a dose of 1 mg/kg of diazepam a reduction of DA turnover can still be observed in the tuberculum olfactorium and nuc. accumbens but not in the nuc. caudatus, due to a high variability of the response in this area. A similar trend is also found with chlordiazepoxide. Thus, changes in limbic DA turnover are observed in doses close to the minimal effective dose (0.6 mg/kg) needed to release punished behavior and to cause anticonvulsive effects, and may therefore be related to these actions of diazepam. For various reasons it is speculated that an increased GABA receptor activity on the DA cell bodies and their dendrites could mainly be involved in causing the reduction of DA turnover observed after benzodiazepines by diminishing the firing rate in the ascending DA pathways, particularly the mesolimbic DA pathways. Evidence for a change of GABA turnover by diazepam has also been found. It is also suggested that the reduction of cortical NE turnover found after benzodiazepines can partly involve an increased GABA receptor activity on the locus ceruleus cells, although the activation of E receptors on these cells cannot be excluded. These effects on locus ceruleus may be partly responsible for the sedation found after benzodiazepines. Diazepam (1 mg/kg) mimics both clonidine and GABA-ergic drugs in reducing blood pressure and slowing respiration rate, but the effects are blocked by picrotoxin but not by piperoxane, an E receptor-blocking agent. In agreement with the view that blockade of the stress-induced increases of NE turnover by benzodiazepines may be related to their antianxiety actions, it was found that the increase in NE turnover elicited by yohimbine, a drug that causes anxiety in man, is blocked by diazepam.", "contents": "The possible involvement of GABA mechanisms in the action of benzodiazepines on central catecholamine neurons. With the use of quantitative microspectrofluorometry, it has been shown that diazepam (10 mg/kg) and chlordiazepoxide (10 mg/kg) reduce DA turnover in the tuberculum olfactorium, nuc. accumbens, the DA islands of the entorhinal cortex, and caput of nuc. caudatus, whereas DA turnover is increased in the lateral external layer of the median eminence after 10 mg/kg of diazepam. It is of considerable interest that with a dose of 1 mg/kg of diazepam a reduction of DA turnover can still be observed in the tuberculum olfactorium and nuc. accumbens but not in the nuc. caudatus, due to a high variability of the response in this area. A similar trend is also found with chlordiazepoxide. Thus, changes in limbic DA turnover are observed in doses close to the minimal effective dose (0.6 mg/kg) needed to release punished behavior and to cause anticonvulsive effects, and may therefore be related to these actions of diazepam. For various reasons it is speculated that an increased GABA receptor activity on the DA cell bodies and their dendrites could mainly be involved in causing the reduction of DA turnover observed after benzodiazepines by diminishing the firing rate in the ascending DA pathways, particularly the mesolimbic DA pathways. Evidence for a change of GABA turnover by diazepam has also been found. It is also suggested that the reduction of cortical NE turnover found after benzodiazepines can partly involve an increased GABA receptor activity on the locus ceruleus cells, although the activation of E receptors on these cells cannot be excluded. These effects on locus ceruleus may be partly responsible for the sedation found after benzodiazepines. Diazepam (1 mg/kg) mimics both clonidine and GABA-ergic drugs in reducing blood pressure and slowing respiration rate, but the effects are blocked by picrotoxin but not by piperoxane, an E receptor-blocking agent. In agreement with the view that blockade of the stress-induced increases of NE turnover by benzodiazepines may be related to their antianxiety actions, it was found that the increase in NE turnover elicited by yohimbine, a drug that causes anxiety in man, is blocked by diazepam."}
{"id": "PMID:242209", "title": "Antihypertensive beta blocking action as related to renin and age: a pharmacologic tool to identify pathogenetic mechanisms in essential hypertension.", "content": "Three hundred fifteen patients with essential hypertension were classified according to low (18 percent), normal (59 percent) or high (23 percent) renin-sodium index. The proportion of patients with low renin hypertension progressively increased with increasing age and blood pressure, there being no difference between the sexes. Two high renin groups emerged: a younger group with early moderate hypertension, and an older group with severe hypertension consequent to possibly ischemic renal disease. Long-term beta blocking monotherapy in 137 patients resulted in a reduction of idastolic pressure to 95 mm Hg or less in 65 percent: 85 percent in those with high and 73 percent in those with normal renin activity; pressure was reduced to this level in only 1 of 24 patients (4 percent) with a low renin index. Antihypertensive efficacy was also related to age, since diastolic pressure was normalized in 80 percent of patients under age 40 years, in 50 percent of those aged 40 to 60 years, but in only 20 percent of those over age 60 years. Age may heolp in patient selection but is no substitute for the more reliable renin index, especially in patients over age 40 years, or with high pressure. Using studiew with propranolol as a standard, similar renin responses were obtained with two cardioselective beta1 type blocking drugs, atenolol and metoprolol, as well as with two nonselective beta2+1 receptor antagonists, LL21945 exhibiting prolonged receptor affinity and oxprenolol in slow release form. These long-acting drugs, which proved effective in single daily doses, could be of value in improving patient compliance...", "contents": "Antihypertensive beta blocking action as related to renin and age: a pharmacologic tool to identify pathogenetic mechanisms in essential hypertension. Three hundred fifteen patients with essential hypertension were classified according to low (18 percent), normal (59 percent) or high (23 percent) renin-sodium index. The proportion of patients with low renin hypertension progressively increased with increasing age and blood pressure, there being no difference between the sexes. Two high renin groups emerged: a younger group with early moderate hypertension, and an older group with severe hypertension consequent to possibly ischemic renal disease. Long-term beta blocking monotherapy in 137 patients resulted in a reduction of idastolic pressure to 95 mm Hg or less in 65 percent: 85 percent in those with high and 73 percent in those with normal renin activity; pressure was reduced to this level in only 1 of 24 patients (4 percent) with a low renin index. Antihypertensive efficacy was also related to age, since diastolic pressure was normalized in 80 percent of patients under age 40 years, in 50 percent of those aged 40 to 60 years, but in only 20 percent of those over age 60 years. Age may heolp in patient selection but is no substitute for the more reliable renin index, especially in patients over age 40 years, or with high pressure. Using studiew with propranolol as a standard, similar renin responses were obtained with two cardioselective beta1 type blocking drugs, atenolol and metoprolol, as well as with two nonselective beta2+1 receptor antagonists, LL21945 exhibiting prolonged receptor affinity and oxprenolol in slow release form. These long-acting drugs, which proved effective in single daily doses, could be of value in improving patient compliance..."}
{"id": "PMID:242210", "title": "Hemodynamic lesions in hypertension.", "content": "Essential hypertension is increasingly recognized as a nonhomogenous disorder by various methods of study. The hemodynamic approach, coupled with clinical determination of the range and lability of blood pressure, has resulted in the description of several subgroups: labile hypertension with normal or elevated cardiac output, fixed or established hypertension with varying cardiac output and advanced hypertension with normal or low cardiac output. There is a tendency to postulate that these categories are stages of one disorder, but this remains to be proved. Still other patients have been described who may be further set off by exceptionally labile or hyperkinetic features. In some hypertensive patients, the peripheral resistance is normal; however, regardless of its numerical value, it is now considered to be increased if it fails to decrease normally in the presence of elevated cardiac output. Because an elevated cardiac output is the hemodynamic function that differentiates these groups, and renovascular hypertension as well, it is the focus of much current work. New interest in the central blood volume, the peripheral veins, and the portal veins and splanchnic circulation is focused on their connection with cardiac out-put. Newly appreciated, too, is the existence of parasympathetic inhibition in hypertension, which not only contributes to elevations of heart rate, cardiac output and possibly renin secretion, but also depresses baroreflex responses. Thus far, hemodynamic and endocrine mechanisms of hypertension have not been studied together, except possibly through the blood volume, which remains a highly controversial topic. In this paper, some recent work in the above areas is reviewed and emphasis is given to studies in man.", "contents": "Hemodynamic lesions in hypertension. Essential hypertension is increasingly recognized as a nonhomogenous disorder by various methods of study. The hemodynamic approach, coupled with clinical determination of the range and lability of blood pressure, has resulted in the description of several subgroups: labile hypertension with normal or elevated cardiac output, fixed or established hypertension with varying cardiac output and advanced hypertension with normal or low cardiac output. There is a tendency to postulate that these categories are stages of one disorder, but this remains to be proved. Still other patients have been described who may be further set off by exceptionally labile or hyperkinetic features. In some hypertensive patients, the peripheral resistance is normal; however, regardless of its numerical value, it is now considered to be increased if it fails to decrease normally in the presence of elevated cardiac output. Because an elevated cardiac output is the hemodynamic function that differentiates these groups, and renovascular hypertension as well, it is the focus of much current work. New interest in the central blood volume, the peripheral veins, and the portal veins and splanchnic circulation is focused on their connection with cardiac out-put. Newly appreciated, too, is the existence of parasympathetic inhibition in hypertension, which not only contributes to elevations of heart rate, cardiac output and possibly renin secretion, but also depresses baroreflex responses. Thus far, hemodynamic and endocrine mechanisms of hypertension have not been studied together, except possibly through the blood volume, which remains a highly controversial topic. In this paper, some recent work in the above areas is reviewed and emphasis is given to studies in man."}
{"id": "PMID:242211", "title": "Abnormal forms of bacteria produced by antibiotics.", "content": "Subinhibitory concentrations of antibiotics can produce in vitro aberrant forms of bacteria that are similar to those observed in specimens and cultures from patients being treated with antibacterial agents. Eight species of bacteria were grown on membranes placed on agar containing subinhibitory concentrations of nine antibiotics. The resulting organisms were examined by Gram stain and electron microscopy. Gram stains showed filamentous and granular forms of enterobacteria with bipolar staining, giant staphylococci, and rodlike pneumococci. Electron micrographs showed changes in the number and distribution of ribosomes in enterobacteria and septum abnormalities in cocci. Such abnormal forms can occasionally simulate the appearance of quite different species, and they may indicate the presence of a subinhibitory antibiotic concentration at the site of infection as a result of prior antibacterial therapy.", "contents": "Abnormal forms of bacteria produced by antibiotics. Subinhibitory concentrations of antibiotics can produce in vitro aberrant forms of bacteria that are similar to those observed in specimens and cultures from patients being treated with antibacterial agents. Eight species of bacteria were grown on membranes placed on agar containing subinhibitory concentrations of nine antibiotics. The resulting organisms were examined by Gram stain and electron microscopy. Gram stains showed filamentous and granular forms of enterobacteria with bipolar staining, giant staphylococci, and rodlike pneumococci. Electron micrographs showed changes in the number and distribution of ribosomes in enterobacteria and septum abnormalities in cocci. Such abnormal forms can occasionally simulate the appearance of quite different species, and they may indicate the presence of a subinhibitory antibiotic concentration at the site of infection as a result of prior antibacterial therapy."}
{"id": "PMID:242213", "title": "Gastric secretion, gastroesophageal reflux and esophagitis.", "content": "Neither gastroesophageal reflux nor esophagitis were found to have a clear-cut relationship with gastric secretory output. Patients with esophagitis had significantly longer periods of reflux than those without esophagitis. It is concluded that the important factor in the genesis of esophagitis is the duration of contact between the esophageal mucosa with gastric contents rather than gastric secretory output.", "contents": "Gastric secretion, gastroesophageal reflux and esophagitis. Neither gastroesophageal reflux nor esophagitis were found to have a clear-cut relationship with gastric secretory output. Patients with esophagitis had significantly longer periods of reflux than those without esophagitis. It is concluded that the important factor in the genesis of esophagitis is the duration of contact between the esophageal mucosa with gastric contents rather than gastric secretory output."}
{"id": "PMID:242214", "title": "Effect of lactulose on rabbits fed on a low residue diet.", "content": "The effect of lactulose (Duphalac) was tested for four months on six rabbits on a low residue diet representative of the diet ingested by the peoples of western civilization. A control group of six rabbits simply had the low residue diet and they developed a very low fecal output, with a mean wet fecal weight measured at monthly intervals varying between 2 and 4.6 gm.; increased transit times of 48 hours and intracolonic pressures which increased over four months from a colonic motility index (CMI) of 12,261 to a CMI of 28,084 in response to neostigmine. The rabbits on diet and lactulose did not develop diarrhea but produced three times the wet fecal weight of the rabbits on diet alone, with a range of mean values from 9.4-12.4 gm.; transit times remained at 24 hours which is normal transit time for rabbits on regular laboratory diet; intracolonic pressures in response to neostigmine rose only from a CMI of 11,652 to a CMI of 14,263 during the four months on diet with lactulose.", "contents": "Effect of lactulose on rabbits fed on a low residue diet. The effect of lactulose (Duphalac) was tested for four months on six rabbits on a low residue diet representative of the diet ingested by the peoples of western civilization. A control group of six rabbits simply had the low residue diet and they developed a very low fecal output, with a mean wet fecal weight measured at monthly intervals varying between 2 and 4.6 gm.; increased transit times of 48 hours and intracolonic pressures which increased over four months from a colonic motility index (CMI) of 12,261 to a CMI of 28,084 in response to neostigmine. The rabbits on diet and lactulose did not develop diarrhea but produced three times the wet fecal weight of the rabbits on diet alone, with a range of mean values from 9.4-12.4 gm.; transit times remained at 24 hours which is normal transit time for rabbits on regular laboratory diet; intracolonic pressures in response to neostigmine rose only from a CMI of 11,652 to a CMI of 14,263 during the four months on diet with lactulose."}
{"id": "PMID:242215", "title": "Physicochemical stability of a preanesthetic mixture of hydroxyzine hydrochloride and atropine sulfate.", "content": "The stability of a combination of hydroxyzine hydrochloride and atropine sulfate stored in syringes was studied. Syringes containing the two drugs were stored at 25 C and 3 C for ten days and analyzed at specific time intervals. Absorption spectra, chromatographic characteristics and pH were determined. Results showed the admixture to be stable for ten days at room temperature or under refrigeration. The technique used would probably not detect any significant degradation of atropine sulfate unless the reaction occurred with the hydroxyzine hydrochloride.", "contents": "Physicochemical stability of a preanesthetic mixture of hydroxyzine hydrochloride and atropine sulfate. The stability of a combination of hydroxyzine hydrochloride and atropine sulfate stored in syringes was studied. Syringes containing the two drugs were stored at 25 C and 3 C for ten days and analyzed at specific time intervals. Absorption spectra, chromatographic characteristics and pH were determined. Results showed the admixture to be stable for ten days at room temperature or under refrigeration. The technique used would probably not detect any significant degradation of atropine sulfate unless the reaction occurred with the hydroxyzine hydrochloride."}
{"id": "PMID:242216", "title": "Stability of parenteral solutions of tobramycin sulfate.", "content": "The stability and physical compatibility of tobramycin sulfate in commonly used intravenous fluids were evaluated; in addition, pH values were obtained on 1 mg/ml tobramycin solutions, and microbiological potencies were obtained on 1 mg/ml and 0.2 mg/ml concentrations for 24- and 48-hour periods at 25 C. Most solutions were stable for 48 hours at room temperature. However, it is recommended that solutions of tobramycin sulfate be discarded after 24 hours to minimize the potential for inadvertent introduction of microorganisms during manipulations in the hospital environment.", "contents": "Stability of parenteral solutions of tobramycin sulfate. The stability and physical compatibility of tobramycin sulfate in commonly used intravenous fluids were evaluated; in addition, pH values were obtained on 1 mg/ml tobramycin solutions, and microbiological potencies were obtained on 1 mg/ml and 0.2 mg/ml concentrations for 24- and 48-hour periods at 25 C. Most solutions were stable for 48 hours at room temperature. However, it is recommended that solutions of tobramycin sulfate be discarded after 24 hours to minimize the potential for inadvertent introduction of microorganisms during manipulations in the hospital environment."}
{"id": "PMID:242218", "title": "Hematological findings in acute infections and septicemias.", "content": "This paper is a report on twelve cases of septicemia, the diagnosis made possible by medical technologists observing the degenerative morphological findings in the peripheral blood smears. This led to the finding of microorganisms, prior to the bacteriological confirmation, in an active emergency department. It also includes four case reports in which the organism was identified: a meningococcus, a pneumonococcus, an Escherichia coli, and a clostridium perfringens (welchii).", "contents": "Hematological findings in acute infections and septicemias. This paper is a report on twelve cases of septicemia, the diagnosis made possible by medical technologists observing the degenerative morphological findings in the peripheral blood smears. This led to the finding of microorganisms, prior to the bacteriological confirmation, in an active emergency department. It also includes four case reports in which the organism was identified: a meningococcus, a pneumonococcus, an Escherichia coli, and a clostridium perfringens (welchii)."}
{"id": "PMID:242220", "title": "Morphologic features of spleen allografts in rats. Graft rejection, acceptance, or lethal graft-versus-host disease in the same donor-recipient pairing.", "content": "The structural changes in serial biopsies of spleen allografts in inbred histoincompatible rats are described. Three experimental procedures in the same donor-recipient pairing (PVG to AGUS) were employed and resulted in spleen graft rejection (Group I, no pretreatment), spleen graft acceptance (Group II, hosts pretreated with donor cells), and lethal GVH disease (Group III, donors pretreated with host cells). Striking features in the three groups were the variation of involvement of the periarterial lymphatic sheaths (PALS) shortly after grafting, and a substantial increase in hemopoiesis, particularly erythropoiesis, in the red pulp. The very \"quiet\" cellular reaction in the PALS of the host spleens in Group II corresponded with permanent graft acceptance. In Group III the previously sensitized allografts behaved rather like Group I host spleens and, by causing fatal GVH disease, demonstrated their immunologic superiority.", "contents": "Morphologic features of spleen allografts in rats. Graft rejection, acceptance, or lethal graft-versus-host disease in the same donor-recipient pairing. The structural changes in serial biopsies of spleen allografts in inbred histoincompatible rats are described. Three experimental procedures in the same donor-recipient pairing (PVG to AGUS) were employed and resulted in spleen graft rejection (Group I, no pretreatment), spleen graft acceptance (Group II, hosts pretreated with donor cells), and lethal GVH disease (Group III, donors pretreated with host cells). Striking features in the three groups were the variation of involvement of the periarterial lymphatic sheaths (PALS) shortly after grafting, and a substantial increase in hemopoiesis, particularly erythropoiesis, in the red pulp. The very \"quiet\" cellular reaction in the PALS of the host spleens in Group II corresponded with permanent graft acceptance. In Group III the previously sensitized allografts behaved rather like Group I host spleens and, by causing fatal GVH disease, demonstrated their immunologic superiority."}
{"id": "PMID:242221", "title": "Histamine H1- and H2-receptors in pulmonary and systemic vasculature of the dog.", "content": "This study was conducted to identify and clarify the actions of pulmonary and systemic H1- and H2-receptors by utilizing specific histamine receptor antagonists. Histamine was infused in anesthetized dogs during control conditions, after H2-receptor blockade with metiamide, after H1-receptor blockade with chlorpheniramine, and after combined H1- and H2-receptor blockade. Histamine infusion, alone, induced marked systemic vasodilatation, pulmonary vasoconstriction, and transient increases in cardiac output and heart rate. H2-receptor blockade prevented the systemic vasocilatation and potentiated the pulmonary vasoconstriction induced by histamine. H1-receptor blockade augmented the systemic vasodilatation, prevented the pulmonary vasoconstriction, and increased the cardiac output and heart rate responses induced by histamine. Thus, H2-receptors appear to mediate the vasocilatation, tachycardia, and increased cardiac output induced by histamine, whereas H1-receptors appear to mediate the vasoconstrictor and the minimal cardiac depressent actions of histamine. Histamine stimulates only H1- and H2-receptors, since combined H1- and H2-receptor antagonism prevented almost all of the cardiovascular actions of histamine.", "contents": "Histamine H1- and H2-receptors in pulmonary and systemic vasculature of the dog. This study was conducted to identify and clarify the actions of pulmonary and systemic H1- and H2-receptors by utilizing specific histamine receptor antagonists. Histamine was infused in anesthetized dogs during control conditions, after H2-receptor blockade with metiamide, after H1-receptor blockade with chlorpheniramine, and after combined H1- and H2-receptor blockade. Histamine infusion, alone, induced marked systemic vasodilatation, pulmonary vasoconstriction, and transient increases in cardiac output and heart rate. H2-receptor blockade prevented the systemic vasocilatation and potentiated the pulmonary vasoconstriction induced by histamine. H1-receptor blockade augmented the systemic vasodilatation, prevented the pulmonary vasoconstriction, and increased the cardiac output and heart rate responses induced by histamine. Thus, H2-receptors appear to mediate the vasocilatation, tachycardia, and increased cardiac output induced by histamine, whereas H1-receptors appear to mediate the vasoconstrictor and the minimal cardiac depressent actions of histamine. Histamine stimulates only H1- and H2-receptors, since combined H1- and H2-receptor antagonism prevented almost all of the cardiovascular actions of histamine."}
{"id": "PMID:242222", "title": "Metabolic and respiratory responses during Helox-induced hypothermia in the white rat.", "content": "Unanesthetized and unrestrained rats, chronically cannulated in the carotid artery, were exposed to normal air (NA) and Helox (21% O2, 79% He) at ambient temperatures (Ta) of 22 and -10 degrees C. In Helox at Ta = 22 degrees C, the Vo2 was 1.39 ml O2/g-h and the Vco2 0.98 ml CO2/g-h, 145 and 126%, respectively, of the values in NA at Ta = 22 degrees C. The arterial Pao2, Paco2, and pH were comparable in Helox and NA at Ta = 22 degrees C. In Helox at Ta = -10 degrees C, rats invariably became hypothermic after exposure of 0.75 to 1.5 h. During the induction of hypothermia the decrease of Vo2 and Vco2 was oscillatory, Pao2 and pH increased, and Paco2 decreased significatnly (P less than 0.05). Minimum Vo2 and Vco2 during hypothermia averaged 0.71 ml O2/g-h and 0.50 ml CO2/g-h, 23 and 22%, respectively, of the values in normothermic animals at Ta = -10 degrees C. Minimum body temperature during hypothermia was clamped at 21.7 +/- 0.3 degrees C (X +/- SE) by increasing Ta to 19 degrees C. When Helox was replaced by NA, hypothermic rats rewarmed spontaneously, returning to normothermia within 4 h. The data suggest that hypothermia induced by Helox plus cold does not seem to be due to respiratory failure, as systemic hypoxia or hypercapnia were not observed. The controlled hypothermia cycle reported here provides a model for dynamic studies of thermogenic mechanisms both at the normothermic and hypothermic states without the interference of drugs and other nonphysiological treatments.", "contents": "Metabolic and respiratory responses during Helox-induced hypothermia in the white rat. Unanesthetized and unrestrained rats, chronically cannulated in the carotid artery, were exposed to normal air (NA) and Helox (21% O2, 79% He) at ambient temperatures (Ta) of 22 and -10 degrees C. In Helox at Ta = 22 degrees C, the Vo2 was 1.39 ml O2/g-h and the Vco2 0.98 ml CO2/g-h, 145 and 126%, respectively, of the values in NA at Ta = 22 degrees C. The arterial Pao2, Paco2, and pH were comparable in Helox and NA at Ta = 22 degrees C. In Helox at Ta = -10 degrees C, rats invariably became hypothermic after exposure of 0.75 to 1.5 h. During the induction of hypothermia the decrease of Vo2 and Vco2 was oscillatory, Pao2 and pH increased, and Paco2 decreased significatnly (P less than 0.05). Minimum Vo2 and Vco2 during hypothermia averaged 0.71 ml O2/g-h and 0.50 ml CO2/g-h, 23 and 22%, respectively, of the values in normothermic animals at Ta = -10 degrees C. Minimum body temperature during hypothermia was clamped at 21.7 +/- 0.3 degrees C (X +/- SE) by increasing Ta to 19 degrees C. When Helox was replaced by NA, hypothermic rats rewarmed spontaneously, returning to normothermia within 4 h. The data suggest that hypothermia induced by Helox plus cold does not seem to be due to respiratory failure, as systemic hypoxia or hypercapnia were not observed. The controlled hypothermia cycle reported here provides a model for dynamic studies of thermogenic mechanisms both at the normothermic and hypothermic states without the interference of drugs and other nonphysiological treatments."}
{"id": "PMID:242219", "title": "Extrahepatic manifestations of viral hepatitis.", "content": "Recent evidence indicates that viral hepatitis is sometimes associated with the production of extrahepatic tissue injury. Hepatitis B virus (HBV) infection is most commonly incriminated but non-type B hepatitis may also be involved. Three types of syndromes have been recognized. First, a serum sickness-like prodrome consisting of skin eruptions, urticaria  and polyarthralgias or arthritis may occur from one to six weeks prior to the onset of hepatitis in 15 to 20 per cent of patients and usually disappears by the time the patient becomes jaundiced. There is extensive evidence that circulating immune complexes are responsible for these symptoms. Second, about 30 to 40 per cent of patients with typical polyarteritis nodosa have persistent hepatitis B surface antigenemia (HBs Ag). Circulating immune complexes composed of HBs Ag, antibody, and complement have been demonstrated together with deposits of immune complexes at sites of vascular injury. Third, an immune complex type of glomerulonephritis may occur following hepatitis B virus infection, usually in association with chronic active hepatitis. Thus there is impressive evidence that hepatitis viruses, especially HBV, may produce a variety of extrahepatic manifestations in which the mechanism of pathogenesis involves an immunologic process rather than direct viral invasion and cytopathogenicity.", "contents": "Extrahepatic manifestations of viral hepatitis. Recent evidence indicates that viral hepatitis is sometimes associated with the production of extrahepatic tissue injury. Hepatitis B virus (HBV) infection is most commonly incriminated but non-type B hepatitis may also be involved. Three types of syndromes have been recognized. First, a serum sickness-like prodrome consisting of skin eruptions, urticaria  and polyarthralgias or arthritis may occur from one to six weeks prior to the onset of hepatitis in 15 to 20 per cent of patients and usually disappears by the time the patient becomes jaundiced. There is extensive evidence that circulating immune complexes are responsible for these symptoms. Second, about 30 to 40 per cent of patients with typical polyarteritis nodosa have persistent hepatitis B surface antigenemia (HBs Ag). Circulating immune complexes composed of HBs Ag, antibody, and complement have been demonstrated together with deposits of immune complexes at sites of vascular injury. Third, an immune complex type of glomerulonephritis may occur following hepatitis B virus infection, usually in association with chronic active hepatitis. Thus there is impressive evidence that hepatitis viruses, especially HBV, may produce a variety of extrahepatic manifestations in which the mechanism of pathogenesis involves an immunologic process rather than direct viral invasion and cytopathogenicity."}
{"id": "PMID:242223", "title": "Adrenergic mechanisms in canine gastric circulation.", "content": "The effects of adrenergic stimulation and blockade on the gastric circulation were studied in anesthetized dogs. Blood flow through the right and left gastric artery was measured electromagnetically. Norepinephrine and isoproterenol were injected intra-arterially and intravenously before and after alpha- and beta-adrenergic blockade. Isoproterenol caused vasodilation of both right and left gastric circulations and this effect was attenuated by beta blockade. Epinephrine and norepinephrine induced constriction followed by dilation in both circulations. The constrictor components were attenuated or abolished by alpha-adrenergic blockade and the dilator components were attenuated by beta-adrenergic blockade. The right and left gastric vascular beds demonstrated quantitatively different responses to the same dose of each adrenergic amine. The left gastric circulation had a greater vasodilator response than did the right gastric circulation. These data support the classical concepts that epinephrine and norepinephrine are \"mixed\" adrenergic agonists and isoproterenol is a \"pure\" beta-adrenerigic agonist. The data further suggest that there is a differential in beta-adrenergic receptor distribution with the left gastric vasculature demonstrating greater dilator responses than the right.", "contents": "Adrenergic mechanisms in canine gastric circulation. The effects of adrenergic stimulation and blockade on the gastric circulation were studied in anesthetized dogs. Blood flow through the right and left gastric artery was measured electromagnetically. Norepinephrine and isoproterenol were injected intra-arterially and intravenously before and after alpha- and beta-adrenergic blockade. Isoproterenol caused vasodilation of both right and left gastric circulations and this effect was attenuated by beta blockade. Epinephrine and norepinephrine induced constriction followed by dilation in both circulations. The constrictor components were attenuated or abolished by alpha-adrenergic blockade and the dilator components were attenuated by beta-adrenergic blockade. The right and left gastric vascular beds demonstrated quantitatively different responses to the same dose of each adrenergic amine. The left gastric circulation had a greater vasodilator response than did the right gastric circulation. These data support the classical concepts that epinephrine and norepinephrine are \"mixed\" adrenergic agonists and isoproterenol is a \"pure\" beta-adrenerigic agonist. The data further suggest that there is a differential in beta-adrenergic receptor distribution with the left gastric vasculature demonstrating greater dilator responses than the right."}
{"id": "PMID:242224", "title": "Effect of volatile fatty acids on water and ion absorption from the goat colon.", "content": "The absorption of volatile fatty acids (VFA) and the influence of VFA on the net transport of inorganic electrolytes and water were examined in the temporarily isolated colon of the conscious goat. Perfusion of the colon with a solution similar in content to that normally present in the cecal outflow showed that the net absorption of VFA was more rapid than that of any other ion present in the solution. When the VFA were replaced with Cl, the net absorption of Na and water was reduced nearly twofold. Increasing the pH of the solution from 6.0 to 7.4 in the presence of VFA also resulted in a twofold decreased in the net transport of Na and water. Perfusion of the colon with a hypertonic solution resulted in approximately zero net water transport; however, the net absorption of Na and VFA continued at similar rates as before. These results support the concept that the colon primarily conserves solute followed by the passive movement of water. They also demonstrate that VFA are rapidly absorbed from the goat colon and indicate a striking influence of VFA on the net transport of Na and water. The presence of VFA in the large intestine may be important for normal absorptive function.", "contents": "Effect of volatile fatty acids on water and ion absorption from the goat colon. The absorption of volatile fatty acids (VFA) and the influence of VFA on the net transport of inorganic electrolytes and water were examined in the temporarily isolated colon of the conscious goat. Perfusion of the colon with a solution similar in content to that normally present in the cecal outflow showed that the net absorption of VFA was more rapid than that of any other ion present in the solution. When the VFA were replaced with Cl, the net absorption of Na and water was reduced nearly twofold. Increasing the pH of the solution from 6.0 to 7.4 in the presence of VFA also resulted in a twofold decreased in the net transport of Na and water. Perfusion of the colon with a hypertonic solution resulted in approximately zero net water transport; however, the net absorption of Na and VFA continued at similar rates as before. These results support the concept that the colon primarily conserves solute followed by the passive movement of water. They also demonstrate that VFA are rapidly absorbed from the goat colon and indicate a striking influence of VFA on the net transport of Na and water. The presence of VFA in the large intestine may be important for normal absorptive function."}
{"id": "PMID:242234", "title": "Lactate, pyruvate, and excess lactate during ether and halothane anesthesia in infants and children.", "content": "Arterial blood lactate, pyruvate, and excess lactate (XL) were measured and calculated in 33 patients aged 7 months to 6 years over a period of 2 hours during repair of harelip or cleft palate. When the anesthetic was diethyl ether, lactate and pyruvate levels rose significantly 60 minutes after induction of anesthesia but did not rise thereafter. Excess lactate appeared 60 minutes after induction of ether anesthesia, but it, too, showed no further increase. When the anesthetic was halothane there was no significant change in lactate, pyruvate, or XL. Changes with ether were not age-related, nor could they be correlated with changes in rectal or skin temperature. The responses of lactate, pyruvate and XL to ether anesthesia in the present study were not significantly different from those found by others in adults.", "contents": "Lactate, pyruvate, and excess lactate during ether and halothane anesthesia in infants and children. Arterial blood lactate, pyruvate, and excess lactate (XL) were measured and calculated in 33 patients aged 7 months to 6 years over a period of 2 hours during repair of harelip or cleft palate. When the anesthetic was diethyl ether, lactate and pyruvate levels rose significantly 60 minutes after induction of anesthesia but did not rise thereafter. Excess lactate appeared 60 minutes after induction of ether anesthesia, but it, too, showed no further increase. When the anesthetic was halothane there was no significant change in lactate, pyruvate, or XL. Changes with ether were not age-related, nor could they be correlated with changes in rectal or skin temperature. The responses of lactate, pyruvate and XL to ether anesthesia in the present study were not significantly different from those found by others in adults."}
{"id": "PMID:242237", "title": "Hypocapnic bronchoconstriction and inhalation anesthetics.", "content": "The effects of halothane, enflurane, and methoxyflurane on hypocapnic bronchoconstriction (increased airway resistance and decreased compliance of the lung) were studied in vivo in the isolated left lower lobe of the canine lung. Hypocapnic bronchoconstriction, induced by altering the concentration of CO2 in gas ventilating the lobe, was repeated in the presence and absence of various concentrations of anesthetic gases (halothane: 0.5, 1.0, and 3.0 per cent; enflurane: 1.0, 3.0, and 5.0 per cent; methoxyflurane: 0.25, 0.50, and 1.0 per cent). In the higher concentrations, all three drugs blocked the bronchoconstrictor effect produced when the inspired CO2 was decreased from 5 to 0 per cent. In lower concentrations, halothane was the most effective blocking drug. Propranolol did not affect the ability of the three anesthetics to block hypocapnic bronchoconstriction, nor did the beta-receptor blocking drug sotalol affect the blocking effects of halothane. The ability of these anesthetics to block hypocapnic bronchoconstriction probably is mediated not through an adrenergic mechanism but by one that is nonspecific. (Key words: Lung, bronchoconstriction; Carbon dioxide, hypocarbia; Anesthetics, volatile, halothane; Anesthetics, volatile, enflurane; Anesthetics, volatile, methoxyflurane.)", "contents": "Hypocapnic bronchoconstriction and inhalation anesthetics. The effects of halothane, enflurane, and methoxyflurane on hypocapnic bronchoconstriction (increased airway resistance and decreased compliance of the lung) were studied in vivo in the isolated left lower lobe of the canine lung. Hypocapnic bronchoconstriction, induced by altering the concentration of CO2 in gas ventilating the lobe, was repeated in the presence and absence of various concentrations of anesthetic gases (halothane: 0.5, 1.0, and 3.0 per cent; enflurane: 1.0, 3.0, and 5.0 per cent; methoxyflurane: 0.25, 0.50, and 1.0 per cent). In the higher concentrations, all three drugs blocked the bronchoconstrictor effect produced when the inspired CO2 was decreased from 5 to 0 per cent. In lower concentrations, halothane was the most effective blocking drug. Propranolol did not affect the ability of the three anesthetics to block hypocapnic bronchoconstriction, nor did the beta-receptor blocking drug sotalol affect the blocking effects of halothane. The ability of these anesthetics to block hypocapnic bronchoconstriction probably is mediated not through an adrenergic mechanism but by one that is nonspecific. (Key words: Lung, bronchoconstriction; Carbon dioxide, hypocarbia; Anesthetics, volatile, halothane; Anesthetics, volatile, enflurane; Anesthetics, volatile, methoxyflurane.)"}
{"id": "PMID:242238", "title": "The ineffectiveness of steroid therapy for treatment of fresh-water near-drowning.", "content": "The authors evaluated the efficacy of continuous positive-pressure ventilation (CPPV) and methylprenisolone alone and in combination as therapy for near-drowning in 80 dogs that had aspirated distilled water (22 ml/kg or 44 ml/kg). Forty dogs were treated with mechanical ventilation for one hour and 40 for 24 hours. Blood-gas tensions, pH, cardiac output and intrapulmonary shunt (Qs/Qt) were measured frequently for 24 hours. Blood-gas tensions and pH were again measured 48 and 72 hours and seven days later in survivors. Arterial oxygen tension (PaO2) decreased and Qs/Qt increased in all animals following aspiration and before therapy. Forty dogs received methylprednisolone intravenously (30 mg/kg) (20 breathed spontaneously and 20 had CPPV). There was a significant increase in PaO2 and decrease in pulmonary shunt in dogs that were ventilated mechanically compared with animals that breathed spontaneously. Treatment with methylprednisolone made no difference in blood gases, pulmonary shunt, or survival rates. Thus, no evidence to support the use of methylprednisolone in the treatment of the pulmonary lesion of fresh-water near-drowning was found. (Key words: Drowning, fresh-water; Hormones, adrenal, methylprednisolone.)", "contents": "The ineffectiveness of steroid therapy for treatment of fresh-water near-drowning. The authors evaluated the efficacy of continuous positive-pressure ventilation (CPPV) and methylprenisolone alone and in combination as therapy for near-drowning in 80 dogs that had aspirated distilled water (22 ml/kg or 44 ml/kg). Forty dogs were treated with mechanical ventilation for one hour and 40 for 24 hours. Blood-gas tensions, pH, cardiac output and intrapulmonary shunt (Qs/Qt) were measured frequently for 24 hours. Blood-gas tensions and pH were again measured 48 and 72 hours and seven days later in survivors. Arterial oxygen tension (PaO2) decreased and Qs/Qt increased in all animals following aspiration and before therapy. Forty dogs received methylprednisolone intravenously (30 mg/kg) (20 breathed spontaneously and 20 had CPPV). There was a significant increase in PaO2 and decrease in pulmonary shunt in dogs that were ventilated mechanically compared with animals that breathed spontaneously. Treatment with methylprednisolone made no difference in blood gases, pulmonary shunt, or survival rates. Thus, no evidence to support the use of methylprednisolone in the treatment of the pulmonary lesion of fresh-water near-drowning was found. (Key words: Drowning, fresh-water; Hormones, adrenal, methylprednisolone.)"}
{"id": "PMID:242242", "title": "[Semiautomatic method of measurement of serum 5'nucleotidase activity].", "content": "A semi-automated method for determining the 5'-nucleotidase activity in human serum for use with the Technicon Autoanalyzer I is described. Based upon the manual method of Persijn and Van Der Slik, adenosine formed by hydrolysis of 5'-AMP is deamined enzymatically and ammonia determined with the Berthelot reaction. The non specific alkaline phosphatases are inhibited by phenylphosphate. Concentrations of 5'-AMP and phenylphosphate are discussed. Nucleotidase activity is determined without dilution up to a value of 210 UI/liter. The precision is better than other manual or semi-automated methods in current use.", "contents": "[Semiautomatic method of measurement of serum 5'nucleotidase activity]. A semi-automated method for determining the 5'-nucleotidase activity in human serum for use with the Technicon Autoanalyzer I is described. Based upon the manual method of Persijn and Van Der Slik, adenosine formed by hydrolysis of 5'-AMP is deamined enzymatically and ammonia determined with the Berthelot reaction. The non specific alkaline phosphatases are inhibited by phenylphosphate. Concentrations of 5'-AMP and phenylphosphate are discussed. Nucleotidase activity is determined without dilution up to a value of 210 UI/liter. The precision is better than other manual or semi-automated methods in current use."}
{"id": "PMID:242243", "title": "Pulmonary arterial wedge pressures: blood gas tensions and pH in the resting horse.", "content": "Blood pressure recordings were made from right atrium, right ventricle, pulmonary trunk, and pulmonary arterial \"wedge\" positions in the standing, resting, adult horse. Similarly, comparisons were made of blood samples collected from these vascular positions, as well as from jugular vein and carotid artery. A consistently lower partial pressure of carbon dioxide and a greater partial pressure of oxygen and pH were found in blood samples from pulmonary arterial wedge than from carotid artery. A technique for safe and rapid collection of pulmonary trunk and pulmonary arterial wedge blood gases, pH, and pressure data, using a balloon-tipped flow-directed catheter, is described in the nonsedated, nontranquilized, resting, adult horse.", "contents": "Pulmonary arterial wedge pressures: blood gas tensions and pH in the resting horse. Blood pressure recordings were made from right atrium, right ventricle, pulmonary trunk, and pulmonary arterial \"wedge\" positions in the standing, resting, adult horse. Similarly, comparisons were made of blood samples collected from these vascular positions, as well as from jugular vein and carotid artery. A consistently lower partial pressure of carbon dioxide and a greater partial pressure of oxygen and pH were found in blood samples from pulmonary arterial wedge than from carotid artery. A technique for safe and rapid collection of pulmonary trunk and pulmonary arterial wedge blood gases, pH, and pressure data, using a balloon-tipped flow-directed catheter, is described in the nonsedated, nontranquilized, resting, adult horse."}
{"id": "PMID:242244", "title": "Cardiopulmonary effects of positive end-expiratory pressure in anesthetized horses.", "content": "The cardiopulmonary effects of 0, 5, 10, and 15 cm of H2O positive end-expiratory pressures (PEEP) were determined in anesthetized, spontaneously breathing horses, using a 4 by 4 Latin-square design with one repetition. Cardiac output, alveolar-arterial oxygen tension difference, alveolar ventilation, dead space/tidal volume ratio, and carbon dioxide elimination were not significantly altered by the procedure. As PEEP was increased, alveolar and arterial oxygen tensions, respiratory exchange ratio, and pH decreased, whereas arterial carbon dioxide tension and oxygen consumption increased. These results indicate PEEP is contraindicated in laterally recumbent spontaneously ventilating anesthetized horses breathing air, because it causes alveolar hypoventilation and does not improve pulmonary gas exchange.", "contents": "Cardiopulmonary effects of positive end-expiratory pressure in anesthetized horses. The cardiopulmonary effects of 0, 5, 10, and 15 cm of H2O positive end-expiratory pressures (PEEP) were determined in anesthetized, spontaneously breathing horses, using a 4 by 4 Latin-square design with one repetition. Cardiac output, alveolar-arterial oxygen tension difference, alveolar ventilation, dead space/tidal volume ratio, and carbon dioxide elimination were not significantly altered by the procedure. As PEEP was increased, alveolar and arterial oxygen tensions, respiratory exchange ratio, and pH decreased, whereas arterial carbon dioxide tension and oxygen consumption increased. These results indicate PEEP is contraindicated in laterally recumbent spontaneously ventilating anesthetized horses breathing air, because it causes alveolar hypoventilation and does not improve pulmonary gas exchange."}
{"id": "PMID:242245", "title": "Mammalian erythrocyte glutathione reductase: kinetic constants and saturation with cofactor.", "content": "Glutathione reductase (GR) was studied in erythrocytes of horses, cats, dogs, and man. Glutathione reductase activity was measured in hemolysates with and without preincubation of hemolysates with flavinadenine dinucleotide. The percentage saturation of GR apoenzyme with cofactor (flavin-adenine dinucleotide) was lower in cats and dogs than in horses or man. The greatest amount of inactive apoenzyme was in feline erythrocytes. Total GR activity listed in order by species is cat greater than man greater than dog greater than horse. Kinetic constants for oxidized glutathione and reduced nicotinamide-adenine dinucleotide phosphate were determined in each species. Although kinetic constant (reduced nicotinamide-adenine dinucleotide phosphate) values for GR were similar, considerable species variation was observed in the kinetic constant (oxidized glutathione) for GR. The kinetic constant (oxidized glutathione) for equine GR was approximately 3 times that for human GR, with intermediate values determined for feline and canine GR.", "contents": "Mammalian erythrocyte glutathione reductase: kinetic constants and saturation with cofactor. Glutathione reductase (GR) was studied in erythrocytes of horses, cats, dogs, and man. Glutathione reductase activity was measured in hemolysates with and without preincubation of hemolysates with flavinadenine dinucleotide. The percentage saturation of GR apoenzyme with cofactor (flavin-adenine dinucleotide) was lower in cats and dogs than in horses or man. The greatest amount of inactive apoenzyme was in feline erythrocytes. Total GR activity listed in order by species is cat greater than man greater than dog greater than horse. Kinetic constants for oxidized glutathione and reduced nicotinamide-adenine dinucleotide phosphate were determined in each species. Although kinetic constant (reduced nicotinamide-adenine dinucleotide phosphate) values for GR were similar, considerable species variation was observed in the kinetic constant (oxidized glutathione) for GR. The kinetic constant (oxidized glutathione) for equine GR was approximately 3 times that for human GR, with intermediate values determined for feline and canine GR."}
{"id": "PMID:242246", "title": "Hemodynamic and metabolic alterations in peripheral tissue during hemorrhagic shock.", "content": "In dogs subjected to hypovolemic shock (modified Wiggers model) severe enough to decrease the arterial flow in an isolated hind limb by two-thirds, a marked hyperglycemia (three times control) and an increase in blood glucose AV difference (ten times control) occur. Despite the decreased arterial flow, glucose uptake by peripheral tissues increased by a factor of three within one-half hour of hemorrhage and remained elevated for several hours. Presumably, the increased glucose uptake reflects the need for more energy substrate during the hypoxic conditions of the decreased peripheral blood flow.", "contents": "Hemodynamic and metabolic alterations in peripheral tissue during hemorrhagic shock. In dogs subjected to hypovolemic shock (modified Wiggers model) severe enough to decrease the arterial flow in an isolated hind limb by two-thirds, a marked hyperglycemia (three times control) and an increase in blood glucose AV difference (ten times control) occur. Despite the decreased arterial flow, glucose uptake by peripheral tissues increased by a factor of three within one-half hour of hemorrhage and remained elevated for several hours. Presumably, the increased glucose uptake reflects the need for more energy substrate during the hypoxic conditions of the decreased peripheral blood flow."}
{"id": "PMID:242248", "title": "Utilization of Fe3+ by the inshore colorless marine dinoflagellate Crypthecodinium cohnii.", "content": "A Puerto Rican isolate of the colorless dinoflagellate Crypthecodinium cohnii was grown in a defined marine medium. Fe was added as Fe(NH4)2(SO3)2 - 6H2O (2.0 mg%), FeCl3 - 6H2O (1.0 mg%) or a particulate slurry prepared from FeCl3 + KOH, along with varying concentrations of several chelators. Heavy growth at pH 7.5-7.7 occurred with salicylhydroxamic acid, aurintricarboxylic acid, EDTA, NTA, and humic acid; and at pH 7.9-8.1 with SHAM and ATA. Moderate growth occurred at pH 7.5-7.7 with sulfosalicylic acid, dipicolinic acid, pyrocatecholdisulfonic acid, hexanohydroxamic acid, L-histidine, and at pH 7.9-8.1 with 1-naphthohydroxamic acid, EDTA, NTA. Slight growth occurred at pH 7.5-7.7 with benzohydroxamic acid, 1-naphohydroxamic acid, 2.6-dipicolinic acid N-oxide, salicylic acid, rhodotorulic acid, Na oxalate, EDDHA, sorbohydroxamic acid, gamma-pyrone-2, 6-decarboxylic acid, and at pH 7.9-8.1 with hexanohydroxamic acid, benzohydroxamic acid. Some ecological and physiological implications are discussed.", "contents": "Utilization of Fe3+ by the inshore colorless marine dinoflagellate Crypthecodinium cohnii. A Puerto Rican isolate of the colorless dinoflagellate Crypthecodinium cohnii was grown in a defined marine medium. Fe was added as Fe(NH4)2(SO3)2 - 6H2O (2.0 mg%), FeCl3 - 6H2O (1.0 mg%) or a particulate slurry prepared from FeCl3 + KOH, along with varying concentrations of several chelators. Heavy growth at pH 7.5-7.7 occurred with salicylhydroxamic acid, aurintricarboxylic acid, EDTA, NTA, and humic acid; and at pH 7.9-8.1 with SHAM and ATA. Moderate growth occurred at pH 7.5-7.7 with sulfosalicylic acid, dipicolinic acid, pyrocatecholdisulfonic acid, hexanohydroxamic acid, L-histidine, and at pH 7.9-8.1 with 1-naphthohydroxamic acid, EDTA, NTA. Slight growth occurred at pH 7.5-7.7 with benzohydroxamic acid, 1-naphohydroxamic acid, 2.6-dipicolinic acid N-oxide, salicylic acid, rhodotorulic acid, Na oxalate, EDDHA, sorbohydroxamic acid, gamma-pyrone-2, 6-decarboxylic acid, and at pH 7.9-8.1 with hexanohydroxamic acid, benzohydroxamic acid. Some ecological and physiological implications are discussed."}
{"id": "PMID:242250", "title": "[Complex rearrangement of chromosomes 3 and 5 in an adolescent with multiple abnormalities].", "content": "Cytogenetic studies were performed on a severely mentally retarded adolescent with multiple congenital abnormalities (congenital heart disease, cryptorchidism and infantilism, rocker bottom feet and eye abnormalities). He had a complex rearrangement as a result of three breaks of chromosome 3 and two breaks of chromosome 5, and haphazard reunion of the fragments. This complex rearrangement appears balanced. The loss of very small chromosome fragments is perhaps the cause of the dysmorphia. The possibility of position effect is discussed.", "contents": "[Complex rearrangement of chromosomes 3 and 5 in an adolescent with multiple abnormalities]. Cytogenetic studies were performed on a severely mentally retarded adolescent with multiple congenital abnormalities (congenital heart disease, cryptorchidism and infantilism, rocker bottom feet and eye abnormalities). He had a complex rearrangement as a result of three breaks of chromosome 3 and two breaks of chromosome 5, and haphazard reunion of the fragments. This complex rearrangement appears balanced. The loss of very small chromosome fragments is perhaps the cause of the dysmorphia. The possibility of position effect is discussed."}
{"id": "PMID:242251", "title": "Acid alpha-glucosidase: a new polymorphism in man demonstrable by 'affinity' electrophoresis.", "content": "1. A new polymorphism of the enzyme acid alpha-glucosidase is described. The three phenotypes, 1, 2-1 and 2, appear to be determined by two alleles alpha-GLU1 and alpha-GLU2 at an autosomal locus. The allele frequencies in Europeans are approximately alpha-GLU1 = 0-97 and alpha-GLU2 = 0-03. 2. The polymorphism is not detectable after electrophoresis on other support media (cellogel and agarose) and evidence is presented that the separation is effected by a difference in binding of the isozyme products of the two alleles to the support medium starch, which contains alpha-1-4 and alpha-1-6 linked glucose units. We have called this type of separation affinity electrophoresis. 3. No difference in the kinetic properties of the two enzymes could be demonstrated using 4-methyl umbelliferyl alpha-D-glucopyranoside and maltose as substrates or maltose and turanose as inhibitors, but it is possible that differences might exist when macromolecular substrates are used. 4. One individual with the rare homozygous genotype has been found. There is at present no indication that this genotype is associated with a pathological condition.", "contents": "Acid alpha-glucosidase: a new polymorphism in man demonstrable by 'affinity' electrophoresis. 1. A new polymorphism of the enzyme acid alpha-glucosidase is described. The three phenotypes, 1, 2-1 and 2, appear to be determined by two alleles alpha-GLU1 and alpha-GLU2 at an autosomal locus. The allele frequencies in Europeans are approximately alpha-GLU1 = 0-97 and alpha-GLU2 = 0-03. 2. The polymorphism is not detectable after electrophoresis on other support media (cellogel and agarose) and evidence is presented that the separation is effected by a difference in binding of the isozyme products of the two alleles to the support medium starch, which contains alpha-1-4 and alpha-1-6 linked glucose units. We have called this type of separation affinity electrophoresis. 3. No difference in the kinetic properties of the two enzymes could be demonstrated using 4-methyl umbelliferyl alpha-D-glucopyranoside and maltose as substrates or maltose and turanose as inhibitors, but it is possible that differences might exist when macromolecular substrates are used. 4. One individual with the rare homozygous genotype has been found. There is at present no indication that this genotype is associated with a pathological condition."}
{"id": "PMID:242252", "title": "Production and property of beta-lactamases in Streptomyces.", "content": "The production of beta-lactamases by 100 strains of Streptomyces was studied. About one-half of the strains produced more than 2.3 U of beta-lactamase per ml, and another half produced less than 1.4 U/ml. The amounts of beta-lactamases produced by two strains were in the order of those produced by Bacillus cereus 569/H and Bacillus licheniformis 749/C. These Streptomyces enzymes function primarily as penicillinases rather than cephalosporinases. Properties such as pH optimum, substrate specificity, and heat stability suggest that these Streptomyces beta-lactamases are closely related to each other. In contrast to bacterial beta-lactamases, Streptomyces beta-lactamases were insusceptible to inactivation by N-bromosuccinimide and only slightly susceptible to iodine. This suggests that the construction mode of the active site would be different from other beta-lactamases. Studies on the minimum inhibitory concentrations of benzylpenicillin to seven Streptomyces strains and on their maximum beta-lactamase production indicate that the susceptibility of Streptomyces to penicillin is not directly related to the beta-lactamase production.", "contents": "Production and property of beta-lactamases in Streptomyces. The production of beta-lactamases by 100 strains of Streptomyces was studied. About one-half of the strains produced more than 2.3 U of beta-lactamase per ml, and another half produced less than 1.4 U/ml. The amounts of beta-lactamases produced by two strains were in the order of those produced by Bacillus cereus 569/H and Bacillus licheniformis 749/C. These Streptomyces enzymes function primarily as penicillinases rather than cephalosporinases. Properties such as pH optimum, substrate specificity, and heat stability suggest that these Streptomyces beta-lactamases are closely related to each other. In contrast to bacterial beta-lactamases, Streptomyces beta-lactamases were insusceptible to inactivation by N-bromosuccinimide and only slightly susceptible to iodine. This suggests that the construction mode of the active site would be different from other beta-lactamases. Studies on the minimum inhibitory concentrations of benzylpenicillin to seven Streptomyces strains and on their maximum beta-lactamase production indicate that the susceptibility of Streptomyces to penicillin is not directly related to the beta-lactamase production."}
{"id": "PMID:242253", "title": "Mechanism of benzoic acid uptake by Saccharomyces cerevisiae.", "content": "A fast uptake of the preservative benzoic acid was observed in Saccharomyces cerevisiae, reaching saturation in about two min and then remaining constant at this level. The strong dependence of benzoic acid uptake on pH was due to the relative distribution of molecular and ionic forms in solution and not to the pH itself. The molecular form was the only one taken up by the cells. The specificity of the uptake mechanism was evidenced by the pattern of irreversible heat inactivation of the uptake system resembling protein denaturation by heat. Furthermore, the effect of temperature on the uptake was similar to that observed in enzymic reactions, whereas the kinetic data of uptake conformed to the Michaelis-Menten curve of saturation with a Km of 1.54 X 10(-2) M and Vmax of 3 X 10(-3) M/10s. The evidence presented in this paper indicates that compounds of protein nature are involved in the uptake of this preservative.", "contents": "Mechanism of benzoic acid uptake by Saccharomyces cerevisiae. A fast uptake of the preservative benzoic acid was observed in Saccharomyces cerevisiae, reaching saturation in about two min and then remaining constant at this level. The strong dependence of benzoic acid uptake on pH was due to the relative distribution of molecular and ionic forms in solution and not to the pH itself. The molecular form was the only one taken up by the cells. The specificity of the uptake mechanism was evidenced by the pattern of irreversible heat inactivation of the uptake system resembling protein denaturation by heat. Furthermore, the effect of temperature on the uptake was similar to that observed in enzymic reactions, whereas the kinetic data of uptake conformed to the Michaelis-Menten curve of saturation with a Km of 1.54 X 10(-2) M and Vmax of 3 X 10(-3) M/10s. The evidence presented in this paper indicates that compounds of protein nature are involved in the uptake of this preservative."}
{"id": "PMID:242254", "title": "Purification and characterization of extracellular proteinases of Aspergillus oryzae.", "content": "The extracellular proteinases of Aspergillus oryzae EI 212 were separated into two active fractions by (NH4)2SO4 and ethanol fractionation followed by diethylaminoethyl-Sephadex A-50 and hydroxyapatite chromatography. The molecular weight was estimated by gel filtration to be about 70,000 and 35,000 for proteinases I and II, respectively. Optimum pH for casein and hemoglobin hydrolysis was 6.5 at 60 C for proteinase I and 10.0 at 45 C for proteinase II, and for gelatin hydrolysis it was 6.5 at 45 C for both enzymes. The enzymes were stable over the pH range 6 to 8 at 30 C for 60 min. The enzyme activity for both the proteinases was accelerated by Cu2+ and inhibited by Fe2+, Fe3+, Hg2+, and Ag+. Halogenators (e.g., N-chlorosuccinimide) and diisopropyl fluorophosphate inhibited proteinase II. Sulfhydryl reagents such as p-chloromercuribenzoate and iodoacetate inhibited proteinase I. Sulfhydryl compounds accelerated the action of both enzymes.", "contents": "Purification and characterization of extracellular proteinases of Aspergillus oryzae. The extracellular proteinases of Aspergillus oryzae EI 212 were separated into two active fractions by (NH4)2SO4 and ethanol fractionation followed by diethylaminoethyl-Sephadex A-50 and hydroxyapatite chromatography. The molecular weight was estimated by gel filtration to be about 70,000 and 35,000 for proteinases I and II, respectively. Optimum pH for casein and hemoglobin hydrolysis was 6.5 at 60 C for proteinase I and 10.0 at 45 C for proteinase II, and for gelatin hydrolysis it was 6.5 at 45 C for both enzymes. The enzymes were stable over the pH range 6 to 8 at 30 C for 60 min. The enzyme activity for both the proteinases was accelerated by Cu2+ and inhibited by Fe2+, Fe3+, Hg2+, and Ag+. Halogenators (e.g., N-chlorosuccinimide) and diisopropyl fluorophosphate inhibited proteinase II. Sulfhydryl reagents such as p-chloromercuribenzoate and iodoacetate inhibited proteinase I. Sulfhydryl compounds accelerated the action of both enzymes."}
{"id": "PMID:242255", "title": "Microbial metabolism of a parathion-xylene pesticide formulation.", "content": "A mixed bacterial culture was adapted to growth on a mixed carbon substrate consisting of the pesticide parathion and its xylene-based formulation. The environmental growth parameters of temperature, pH, and  dissolved oxygen concentration were optimized to obtain complete metabolism of parathion from this mixed carbon substrate. This adapted culture grew rapidly (mu = 0.7 per h) on the pesticide formulation at high parathion suspensions (3,000 mg/liter). Carbon utilization from this mixed substrate was strongly dependent on pH. At slightly acidic pH, xylene was preferentially metabolized, whereas at slightly alkaline pH, parathion was preferentially metabolized. Diethylthiophosphoric acid, a metabolite from parathion, and toluic acid, a metabolite from xylene, also influenced the selection of the primary carbon source.", "contents": "Microbial metabolism of a parathion-xylene pesticide formulation. A mixed bacterial culture was adapted to growth on a mixed carbon substrate consisting of the pesticide parathion and its xylene-based formulation. The environmental growth parameters of temperature, pH, and  dissolved oxygen concentration were optimized to obtain complete metabolism of parathion from this mixed carbon substrate. This adapted culture grew rapidly (mu = 0.7 per h) on the pesticide formulation at high parathion suspensions (3,000 mg/liter). Carbon utilization from this mixed substrate was strongly dependent on pH. At slightly acidic pH, xylene was preferentially metabolized, whereas at slightly alkaline pH, parathion was preferentially metabolized. Diethylthiophosphoric acid, a metabolite from parathion, and toluic acid, a metabolite from xylene, also influenced the selection of the primary carbon source."}
{"id": "PMID:242278", "title": "Effects of adrenergic stimulating and blocking agents on the eccrine sweat secretion in atopic dermatitis and psoriasis.", "content": "Quantitative measurements of eccrine sweat secretion following stimulation with adrenaline and terbutaline sulphate, a beta-stimulator, have been performed in patients with atopic dermatitis and psoriasis by means of the electrolytic water analyzer, \"Meeco\". Seasonal variations were demonstrated, the values being lower in the late autumn. The response to adrenaline could be blocked by phentolamine, an alpha-inhibitor, while propranolol, a beta inhibitor, had no effect.--The response to terbutaline was blocked by atropine and partly by practolol, a beta-inhibitor. Terbutaline induced a larger sweat response than isoprenaline, another beta-stimulator. A beta-receptor mechanism, in some way related to cholinergic receptors, is suggested.", "contents": "Effects of adrenergic stimulating and blocking agents on the eccrine sweat secretion in atopic dermatitis and psoriasis. Quantitative measurements of eccrine sweat secretion following stimulation with adrenaline and terbutaline sulphate, a beta-stimulator, have been performed in patients with atopic dermatitis and psoriasis by means of the electrolytic water analyzer, \"Meeco\". Seasonal variations were demonstrated, the values being lower in the late autumn. The response to adrenaline could be blocked by phentolamine, an alpha-inhibitor, while propranolol, a beta inhibitor, had no effect.--The response to terbutaline was blocked by atropine and partly by practolol, a beta-inhibitor. Terbutaline induced a larger sweat response than isoprenaline, another beta-stimulator. A beta-receptor mechanism, in some way related to cholinergic receptors, is suggested."}
{"id": "PMID:242279", "title": "Nucleation of monosodium urate crystals.", "content": "(1) Calcium greatly increased crystallization of monosodium urate in otherwise pure water, by enhancing both nucleation and growth. (2) Acid accelerated urate nucleation, both by its direct action and indirectly by increasing the free calcium in physiological fluids. (3) Synovial fluid from one gouty patient accelerated urate nucleation, while that from one rheumatoid patient inhibited nucleation. (4) X-rays, collagen, ethyl alcohol, cupric ion, and potassium ion all had negligible influence on urate nucleation. (5) Mechanical shock greatly increased urate nucleation.", "contents": "Nucleation of monosodium urate crystals. (1) Calcium greatly increased crystallization of monosodium urate in otherwise pure water, by enhancing both nucleation and growth. (2) Acid accelerated urate nucleation, both by its direct action and indirectly by increasing the free calcium in physiological fluids. (3) Synovial fluid from one gouty patient accelerated urate nucleation, while that from one rheumatoid patient inhibited nucleation. (4) X-rays, collagen, ethyl alcohol, cupric ion, and potassium ion all had negligible influence on urate nucleation. (5) Mechanical shock greatly increased urate nucleation."}
{"id": "PMID:242280", "title": "Massive Ringer's lactate infusion: comparison with dextrose 5% and whole blood.", "content": "The objectives of this study were to compare in dogs the effects of massive infusion of Ringer's lactate, 5% dextrose in water, and whole blood. Special interest centered upon lung function, central venous pressure, and dilutional effects upon the blood components. Three groups of 5 healthy dogs each received respectively Ringer's lactate, 5% dextrose, or whole blood over 60 minutes in the amount of 135 ml/kg. Arterial blood gases and pH, right atrial and systemic arterial pressures, hemoglobin and hematocrit values, and plasma sodium, chloride, potassium and protein levels were determined. Coagulograms and serum osmolality were examined in the early experiments. The purpose of the whole blood infusion was primarily to serve for comparison in the study of dilutional effects upon blood components. There was no statistically significant change in the arterial blood gas values or pH following Ringer's lactate infusion. The infusion of 5% dextrose in water produced moderate decline in arterial Pco2 and a temporary, slight fall in blood pH. Ringer's lactate infusion produced a prompt and statistically significant rise in central venous pressure. The infusion of 5% dextrose was followed by a late moderate decline in arterial blood pressure, possibly due to marked dilution of plasma sodium, chloride and potassium. It is concluded that massive Ringer's lactate infusion is capable of increasing right atrial pressure and presumably cardiac output. In healthy dogs, lung function was not impaired sufficiently to alter arterial blood gas values. However, where other previous or concomitant factors have diminished pulmonary reserve, fluid overload may impose a serious additional burden upon cardiopulmonary function.", "contents": "Massive Ringer's lactate infusion: comparison with dextrose 5% and whole blood. The objectives of this study were to compare in dogs the effects of massive infusion of Ringer's lactate, 5% dextrose in water, and whole blood. Special interest centered upon lung function, central venous pressure, and dilutional effects upon the blood components. Three groups of 5 healthy dogs each received respectively Ringer's lactate, 5% dextrose, or whole blood over 60 minutes in the amount of 135 ml/kg. Arterial blood gases and pH, right atrial and systemic arterial pressures, hemoglobin and hematocrit values, and plasma sodium, chloride, potassium and protein levels were determined. Coagulograms and serum osmolality were examined in the early experiments. The purpose of the whole blood infusion was primarily to serve for comparison in the study of dilutional effects upon blood components. There was no statistically significant change in the arterial blood gas values or pH following Ringer's lactate infusion. The infusion of 5% dextrose in water produced moderate decline in arterial Pco2 and a temporary, slight fall in blood pH. Ringer's lactate infusion produced a prompt and statistically significant rise in central venous pressure. The infusion of 5% dextrose was followed by a late moderate decline in arterial blood pressure, possibly due to marked dilution of plasma sodium, chloride and potassium. It is concluded that massive Ringer's lactate infusion is capable of increasing right atrial pressure and presumably cardiac output. In healthy dogs, lung function was not impaired sufficiently to alter arterial blood gas values. However, where other previous or concomitant factors have diminished pulmonary reserve, fluid overload may impose a serious additional burden upon cardiopulmonary function."}
{"id": "PMID:242281", "title": "The pathophysiology of smoke inhalation injury.", "content": "The consequences of near-lethal smoke inhalation in dogs were studied for a 72-hour period following injury. Progressive hypoxemia and decrease in compliance developed. Severe respiratory distress and frank pulmonary edema were not encountered. Respiratory insufficiecy was related more to alterations in ventilation perfusion ratios than to alveolar destruction. These data were related to clinical observations made by others. No deterioration of lung function was seen with crystalloid overload imposed upon smoke inhalation. The presence of bacterial infection in dogs surviving beyond 24 hours appears pathogenically significant.", "contents": "The pathophysiology of smoke inhalation injury. The consequences of near-lethal smoke inhalation in dogs were studied for a 72-hour period following injury. Progressive hypoxemia and decrease in compliance developed. Severe respiratory distress and frank pulmonary edema were not encountered. Respiratory insufficiecy was related more to alterations in ventilation perfusion ratios than to alveolar destruction. These data were related to clinical observations made by others. No deterioration of lung function was seen with crystalloid overload imposed upon smoke inhalation. The presence of bacterial infection in dogs surviving beyond 24 hours appears pathogenically significant."}
{"id": "PMID:242282", "title": "A comparison in vivo dacron wool (Swank) and polyester mesh (Pall) micropore blood transfusion filters in the prevention of pulmonary microembolism associated with massive transfusion.", "content": "Experiments were performed to compare the effectiveness in vivo of the two most widely used micropore blood transfusion filters in preventing detrimental physiologic changes associated with transfusion of microaggregate-containing blood. Exchange transfusion with stored blood having an elevated screen filtration pressure (SFP) through polyester mesh (Pall) filters (Group PM) was followed by decreases in arterial blood pH and O2 consumption, increases in arterial blood pyruvate and lactate concentrations, and a decrease in pulmonary DO2. The lungs of 5 of 6 animals revealed emboli far out in the pulmonary microcirculation. These changes did not occur in animals transfused through dacron wool (Swank) filters (Group DW). Even though an increase after transfusion in pulmonary Qs/Qt in Group PM did not achieve statistical significance when compared to pretransfusion Qs/Qt, it was significantly higher than that in animals in Group DW. Both filters removed considerable quantities of microaggregates; however, the polyester mesh (Pall) filters permitted passage of small microaggregates and development of ditrimental physiologic changes. Dacron wool (Swank) filters completely removed measurable microaggregates and detrimental changes did not occur.", "contents": "A comparison in vivo dacron wool (Swank) and polyester mesh (Pall) micropore blood transfusion filters in the prevention of pulmonary microembolism associated with massive transfusion. Experiments were performed to compare the effectiveness in vivo of the two most widely used micropore blood transfusion filters in preventing detrimental physiologic changes associated with transfusion of microaggregate-containing blood. Exchange transfusion with stored blood having an elevated screen filtration pressure (SFP) through polyester mesh (Pall) filters (Group PM) was followed by decreases in arterial blood pH and O2 consumption, increases in arterial blood pyruvate and lactate concentrations, and a decrease in pulmonary DO2. The lungs of 5 of 6 animals revealed emboli far out in the pulmonary microcirculation. These changes did not occur in animals transfused through dacron wool (Swank) filters (Group DW). Even though an increase after transfusion in pulmonary Qs/Qt in Group PM did not achieve statistical significance when compared to pretransfusion Qs/Qt, it was significantly higher than that in animals in Group DW. Both filters removed considerable quantities of microaggregates; however, the polyester mesh (Pall) filters permitted passage of small microaggregates and development of ditrimental physiologic changes. Dacron wool (Swank) filters completely removed measurable microaggregates and detrimental changes did not occur."}
{"id": "PMID:242283", "title": "Postoperative arterial blood gas measurement in obese patients: effect of position on gas exchange.", "content": "The effect of position change on blood gas exchange was studied in 22 markedly obese, otherwise healthy, women both preoperatively and postoperatively. There was a statistically significant decrease in arterial oxygen tension and a simultaneous reduction both in the arterial carbon dioxide tension and the base excess with the assumption of the supine versus the semirecumbent position on postoperative days one and two. However, no positional difference was demonstrable in any variable by the third postoperative day. This study indicates that in obese patients during the first 48 hours after abdominal surgery, assumption and maintenance of the semirecumbent posture is a valuable therapeutic adjunct to improve arterial oxygenation.", "contents": "Postoperative arterial blood gas measurement in obese patients: effect of position on gas exchange. The effect of position change on blood gas exchange was studied in 22 markedly obese, otherwise healthy, women both preoperatively and postoperatively. There was a statistically significant decrease in arterial oxygen tension and a simultaneous reduction both in the arterial carbon dioxide tension and the base excess with the assumption of the supine versus the semirecumbent position on postoperative days one and two. However, no positional difference was demonstrable in any variable by the third postoperative day. This study indicates that in obese patients during the first 48 hours after abdominal surgery, assumption and maintenance of the semirecumbent posture is a valuable therapeutic adjunct to improve arterial oxygenation."}
{"id": "PMID:242284", "title": "On the narcotic cuing action of fentanyl and other narcotic analgesic drugs.", "content": "Using a food-reinforced two-levers operant procedure, rats could be trained to discriminate fentanyl (1.25 mg/kg, p.o., t-60') from solvent (1 ml/100 g B.W., p.o.,t60)treatment. The administration of the other narcotic analgesics bezitramide, dextromoramide, methadone and morphine produced a dose-related stimulus generalization with the standard fentanyl treatment. The results further evidence the validity of the narcotic cue.", "contents": "On the narcotic cuing action of fentanyl and other narcotic analgesic drugs. Using a food-reinforced two-levers operant procedure, rats could be trained to discriminate fentanyl (1.25 mg/kg, p.o., t-60') from solvent (1 ml/100 g B.W., p.o.,t60)treatment. The administration of the other narcotic analgesics bezitramide, dextromoramide, methadone and morphine produced a dose-related stimulus generalization with the standard fentanyl treatment. The results further evidence the validity of the narcotic cue."}
{"id": "PMID:242285", "title": "The effects of three benzodiazepines and of meprobamate on the action of smooth muscle stimulants on the guinea-pig ileum.", "content": "The benzodiazepines chlorodiazepoxide, diazepam and flurazepam and meprobamate depress the response of the guinea-pig ileum to acetylcholine, histamine and 5-hydroxytryptamine. As compared to the benzodiazepines the action of meprobamate is very weak. Chlorodiazepoxide has a weaker anti-acetylcholine activity than diazepam and flurazepam. On the other hand chlorodiazepoxide possesses a realtively strong anti-histamine activity. The three benzodiazeptines tested are about equally effective in reducing the contraction of the guinea-pig ileum caused by 5-hydroxytryptamine. The potency of diazepam and flurazepam in blocking the effect of the three smooth muscle stimulants appears to be rather similar.", "contents": "The effects of three benzodiazepines and of meprobamate on the action of smooth muscle stimulants on the guinea-pig ileum. The benzodiazepines chlorodiazepoxide, diazepam and flurazepam and meprobamate depress the response of the guinea-pig ileum to acetylcholine, histamine and 5-hydroxytryptamine. As compared to the benzodiazepines the action of meprobamate is very weak. Chlorodiazepoxide has a weaker anti-acetylcholine activity than diazepam and flurazepam. On the other hand chlorodiazepoxide possesses a realtively strong anti-histamine activity. The three benzodiazeptines tested are about equally effective in reducing the contraction of the guinea-pig ileum caused by 5-hydroxytryptamine. The potency of diazepam and flurazepam in blocking the effect of the three smooth muscle stimulants appears to be rather similar."}
{"id": "PMID:242286", "title": "Pharmacological characteristics of the responses of rabbit oviduct to transmural stimulation.", "content": "The nature of the response of oestrogen dominant rabbit oviduct to transmural stimulation has been investigated. Both ampulla and isthmus responded to transmural stimulation with a single maintained response. This response was abolished by phentolamine, guanethidine, tetradotoxin and 6-hydroxydopamine showing that it resulted from the release of noradrenaline from adrenergic nerves and an action on alpha receptors. Propranolol had no effect on the responses of circular isthmic muscle suggesting that the beta receptors were relatively unimportant in determining the magnitude of the response. Cocaine failed to potentiate the magnitude of the response to field stimulation but did prolong the duration of the response. UO521, an inhibitor of COMT, had no effect on the responses of circular isthmus to transmural.", "contents": "Pharmacological characteristics of the responses of rabbit oviduct to transmural stimulation. The nature of the response of oestrogen dominant rabbit oviduct to transmural stimulation has been investigated. Both ampulla and isthmus responded to transmural stimulation with a single maintained response. This response was abolished by phentolamine, guanethidine, tetradotoxin and 6-hydroxydopamine showing that it resulted from the release of noradrenaline from adrenergic nerves and an action on alpha receptors. Propranolol had no effect on the responses of circular isthmic muscle suggesting that the beta receptors were relatively unimportant in determining the magnitude of the response. Cocaine failed to potentiate the magnitude of the response to field stimulation but did prolong the duration of the response. UO521, an inhibitor of COMT, had no effect on the responses of circular isthmus to transmural."}
{"id": "PMID:242287", "title": "Cinnarizine and flunarizine, potent inhibitors of anaphylactic shock in guinea-pigs.", "content": "Histamine-induced paw oedema and anaphylactic shock were studied simultaneously in ovalbumin-sensitized guinea-pigs and cinnarizine and flunarizine were evaluated quantitatively with regard to protection from the two types of challenge. Both compounds were markedly more active in preventing lethal anaphylaxis (ED50's of 0.67 and 0.53 mg/kg OR) than in reducing histamine oedema (ED50's of 2.77 and 1.54 mg/kg OR). The high anti-anaphylactic potency after oral administration may be an important finding in view of the therapeutic applications of cinnarizine and flunarizine.", "contents": "Cinnarizine and flunarizine, potent inhibitors of anaphylactic shock in guinea-pigs. Histamine-induced paw oedema and anaphylactic shock were studied simultaneously in ovalbumin-sensitized guinea-pigs and cinnarizine and flunarizine were evaluated quantitatively with regard to protection from the two types of challenge. Both compounds were markedly more active in preventing lethal anaphylaxis (ED50's of 0.67 and 0.53 mg/kg OR) than in reducing histamine oedema (ED50's of 2.77 and 1.54 mg/kg OR). The high anti-anaphylactic potency after oral administration may be an important finding in view of the therapeutic applications of cinnarizine and flunarizine."}
{"id": "PMID:242288", "title": "The role of the central nervous system in the cardiovascular responses to yohimbine.", "content": "Yohimbine injected intravenously or intracerebroventricularly in conscious dogs produced behavioural excitation accompanied by a rise in blood pressure and heart rate. The cardiovascular effects were reduced or abolished by hexamethonium, phenoxybenzamine and reserpine. In conscious cats intravenously administered yohimbine was depressor but intracerebroventricular administration in these animals caused a rise in blood pressure accompanied by behavioural depression. In anaesthetized or decerebrate cats yohimbine was always depressor. Yohimbine injected intracerebroventricularly produced a rise in blood pressure and heart rate in both conscious and anaesthetized rats. When administered intravenously to these animals there was a fall in blood pressure. It was concluded that the pressor action of yohimbine in conscious dogs was central in origin via the sympathetic nervous system. The different pattern of cardiovascular responses in the dog, cat and rat may be related to differences in the balance between medullary effects and effects on higher brain centres of the three species.", "contents": "The role of the central nervous system in the cardiovascular responses to yohimbine. Yohimbine injected intravenously or intracerebroventricularly in conscious dogs produced behavioural excitation accompanied by a rise in blood pressure and heart rate. The cardiovascular effects were reduced or abolished by hexamethonium, phenoxybenzamine and reserpine. In conscious cats intravenously administered yohimbine was depressor but intracerebroventricular administration in these animals caused a rise in blood pressure accompanied by behavioural depression. In anaesthetized or decerebrate cats yohimbine was always depressor. Yohimbine injected intracerebroventricularly produced a rise in blood pressure and heart rate in both conscious and anaesthetized rats. When administered intravenously to these animals there was a fall in blood pressure. It was concluded that the pressor action of yohimbine in conscious dogs was central in origin via the sympathetic nervous system. The different pattern of cardiovascular responses in the dog, cat and rat may be related to differences in the balance between medullary effects and effects on higher brain centres of the three species."}
{"id": "PMID:242289", "title": "The role of bronchoconstrictors in evaluating smooth muscle relaxant activity.", "content": "Several bronchoconstrictor and smooth muscle relaxant agents were studied in a dog preparation (in vivo) and on guinea pig tracheal strips (in vitro). Isoproterenol, isoetharine and N-t-butylnorepinephrine, individually, had similar dose-response curves and ED50 values when tested as antagonists of histamine and carbamylcholine-induced bronchoconstriction in dogs. Diphenhydramine, cyproheptadine, thenyldiamine, atropine and suloxifen each exhibited more selective antagonism. A ratio of anticholinergic and antihistamine ED50s was obtained in dogs and on guinea pig tracheal strips. The rank order correlation coefficient of this ratio for each drug in the two species (rs = 0.93) was highly significant. Dose-responses to smooth muscle relaxant effects of isoproterenol were obtained with several different constrictors and experimental conditions on guinea pig tracheal strips. The choice of a constrictor and experimental conditions was found to affect EC50 values. The influence of resting tension, temperature, season, dibenamine-pretreatment and manner of performing the dose-response was evaluated. Both Ba and carbamylcholine were found to be suitable constricting agents under various conditions, whereas histamine, serotonin, potassium and rubidium had more limitations and eight other inorganic ions were not suitable.", "contents": "The role of bronchoconstrictors in evaluating smooth muscle relaxant activity. Several bronchoconstrictor and smooth muscle relaxant agents were studied in a dog preparation (in vivo) and on guinea pig tracheal strips (in vitro). Isoproterenol, isoetharine and N-t-butylnorepinephrine, individually, had similar dose-response curves and ED50 values when tested as antagonists of histamine and carbamylcholine-induced bronchoconstriction in dogs. Diphenhydramine, cyproheptadine, thenyldiamine, atropine and suloxifen each exhibited more selective antagonism. A ratio of anticholinergic and antihistamine ED50s was obtained in dogs and on guinea pig tracheal strips. The rank order correlation coefficient of this ratio for each drug in the two species (rs = 0.93) was highly significant. Dose-responses to smooth muscle relaxant effects of isoproterenol were obtained with several different constrictors and experimental conditions on guinea pig tracheal strips. The choice of a constrictor and experimental conditions was found to affect EC50 values. The influence of resting tension, temperature, season, dibenamine-pretreatment and manner of performing the dose-response was evaluated. Both Ba and carbamylcholine were found to be suitable constricting agents under various conditions, whereas histamine, serotonin, potassium and rubidium had more limitations and eight other inorganic ions were not suitable."}
{"id": "PMID:242290", "title": "Effect of temperature, salts, pH, and other factors on the development of peritrichous flagella in Vibrio alginolyticus.", "content": "The development of peritrichous flagella and, consequently, swarming of Vibrio alginolyticus depend on a complex relationship between temperature, salt concentrations and pH. At temperatures above 28 degrees C V. alginolyticus did not develop peritrichous flagella unless certain minimal concentrations of NaCl are present: the higher the temperature, the higher the NaCl concentrations required for peritrichous flagella synthesis. This requirement for NaCl at high temperatures is much more pronounced at pH 9 than at pH 6. High temperatures and low concentrations of NaCl also inhibited swarming of cells already armed with peritrichous flagella. Other cations, such as Li+, K+ and Mg2+. replaced NaCl only at temperatures below 28 degrees C.", "contents": "Effect of temperature, salts, pH, and other factors on the development of peritrichous flagella in Vibrio alginolyticus. The development of peritrichous flagella and, consequently, swarming of Vibrio alginolyticus depend on a complex relationship between temperature, salt concentrations and pH. At temperatures above 28 degrees C V. alginolyticus did not develop peritrichous flagella unless certain minimal concentrations of NaCl are present: the higher the temperature, the higher the NaCl concentrations required for peritrichous flagella synthesis. This requirement for NaCl at high temperatures is much more pronounced at pH 9 than at pH 6. High temperatures and low concentrations of NaCl also inhibited swarming of cells already armed with peritrichous flagella. Other cations, such as Li+, K+ and Mg2+. replaced NaCl only at temperatures below 28 degrees C."}
{"id": "PMID:242291", "title": "Observations on enzymes of ammonia assimilation in two different strains of Cyanidium caldarium.", "content": "Two strains of Cyanidium caldarium, one able to utilize nitrate as a substrate, and the other not, were tested for the presence of enzymes of ammonia assimilation. The nitrate-assimilating strain exhibits glutamate dehydrogenase activity. By contrast, the other strain lacks glutamate dehydrogenase; it possesses high alanine dehydrogenase and L-alanine aminotransferase activities which suggest that this strain may incorporate ammonia through reductive amination of pyruvate and may form glutamate from 2-ketoglutarate by a transamination reaction with alanine. Neither strain reveals glutamate synthase activity. Both strains contain similar levels of glutamine synthetase.", "contents": "Observations on enzymes of ammonia assimilation in two different strains of Cyanidium caldarium. Two strains of Cyanidium caldarium, one able to utilize nitrate as a substrate, and the other not, were tested for the presence of enzymes of ammonia assimilation. The nitrate-assimilating strain exhibits glutamate dehydrogenase activity. By contrast, the other strain lacks glutamate dehydrogenase; it possesses high alanine dehydrogenase and L-alanine aminotransferase activities which suggest that this strain may incorporate ammonia through reductive amination of pyruvate and may form glutamate from 2-ketoglutarate by a transamination reaction with alanine. Neither strain reveals glutamate synthase activity. Both strains contain similar levels of glutamine synthetase."}
{"id": "PMID:242292", "title": "The nitrate-reducing enzyme system of Chlamydomonas reinhardii.", "content": "In Chlamydomonas reinhardii the reduction of nitrate to ammonia occurs in two independent enzymatic steps: 1. the two-electrons reduction of nitrate to nitrite catalyzed by NADH-nitrate reductase, and, 2. the six-electrons reduction of nitrite to ammonia catalyzed by ferredoxin-nitrite reductase. Both enzymes have been purified and characterized, and some of their properties have been studied.", "contents": "The nitrate-reducing enzyme system of Chlamydomonas reinhardii. In Chlamydomonas reinhardii the reduction of nitrate to ammonia occurs in two independent enzymatic steps: 1. the two-electrons reduction of nitrate to nitrite catalyzed by NADH-nitrate reductase, and, 2. the six-electrons reduction of nitrite to ammonia catalyzed by ferredoxin-nitrite reductase. Both enzymes have been purified and characterized, and some of their properties have been studied."}
{"id": "PMID:242293", "title": "Adsorption and selection of rhizobia with ion-exchange papers.", "content": "Ion exchange papers were used to study the adsorption of 32P-labelled rhizobia on defined surfaces. Two strains of Rhizobium japonicum and one each of R. leguminosarum and R. lupini were compared with Escherichia coli and Bacillus subtilis. The ratio of adsorption to strong and to weak acid papers/strong and weak basic papers was consistantly higher for all rhizobial strains compared to the other bacteria. The process of desorption by increasing the ion-concentration causes about 35% desorption between 0.02 and 0.1 M MgCl2, however, an increase to 1 M does not desorb more labelled Rhizobium japonicum or E. coli cells. The ratio of adsorbed cpm to colony formers, desorbed by 0.1 M NaCl was similar with Rhizobium japonicum for all six ion exchange papers. For E. coli this ratio varied widely for the different papers. The selection of Rhizobium against a more closely related bacterium by this adsorption/desorption procedure was demonstrated with mixed cultures of Rhizobium japonicum and Chromobacterium violaceum giving a more than 80 fold enrichment of the former. Rhizobium japonicum cells, ad/desorbed from all ion exchange papers kept their infectivity and formed nodules on Glycine max with an activity of 20-40 nM C2H4-hr(-1)-mg nodule(-1). A desorption of Rhizobium japonicum from soybean roots also occurred by increasing the ion concentration. 2-3 times as many cells were removed in this way compared to washing with water.", "contents": "Adsorption and selection of rhizobia with ion-exchange papers. Ion exchange papers were used to study the adsorption of 32P-labelled rhizobia on defined surfaces. Two strains of Rhizobium japonicum and one each of R. leguminosarum and R. lupini were compared with Escherichia coli and Bacillus subtilis. The ratio of adsorption to strong and to weak acid papers/strong and weak basic papers was consistantly higher for all rhizobial strains compared to the other bacteria. The process of desorption by increasing the ion-concentration causes about 35% desorption between 0.02 and 0.1 M MgCl2, however, an increase to 1 M does not desorb more labelled Rhizobium japonicum or E. coli cells. The ratio of adsorbed cpm to colony formers, desorbed by 0.1 M NaCl was similar with Rhizobium japonicum for all six ion exchange papers. For E. coli this ratio varied widely for the different papers. The selection of Rhizobium against a more closely related bacterium by this adsorption/desorption procedure was demonstrated with mixed cultures of Rhizobium japonicum and Chromobacterium violaceum giving a more than 80 fold enrichment of the former. Rhizobium japonicum cells, ad/desorbed from all ion exchange papers kept their infectivity and formed nodules on Glycine max with an activity of 20-40 nM C2H4-hr(-1)-mg nodule(-1). A desorption of Rhizobium japonicum from soybean roots also occurred by increasing the ion concentration. 2-3 times as many cells were removed in this way compared to washing with water."}
{"id": "PMID:242294", "title": "Properties and regulation of ribulose diphosphate carboxylase from Thiobacillus novellus.", "content": "Ribulose-diphosphate carboxylase from Thiobacillus novellus has been purified to hemogeneity as observed by polyacrylamide gel electrophoresis and U.V. light observation during sedimentation velocity analysis. The optimum pH for the enzyme with Tris-HCl buffers was about 8.2. Concentrations of this buffer in excess of 80 mM were inhibitory. The apparent Km for RuDP was about 14.8 muM with a Hill value of 1.5, for HCO3- the apparent Km was about 11.7 mM with an n value of 1.18 and for Mg2+ about 0.61 mM. The enzyme was specific for this cation. Relatively high concentrations of either Hg2+ or pCMB were required before significant inhibition was observed. Activity declined slowly during a 4-hr incubation period in either 3.0 M or 8.0 M urea. Incubation for 12 hrs resulted in complete loss of activity which was not prevented by 10 mM Mg2+ and was not reversed by dialysis and subsequent addition of 10 mM cysteine. Polyacrylamide gel electrophoresis revealed a loss of the major band and the appearance of 2 new bands. SDS polyacrylamide gel electrophoresis gave an average M.W. of 73500 +/- 2500 for the slower moving band and 12250 +/- 2500 for the faster moving. However, incubation in urea for up to 40 hrs revealed a decrease in the M.W. of the slower moving band to about 60000. The Ea for the enzyme was calculated to be about 18.85 kcal mole-1, with the possibility of a \"break\" between 40 and 50 degrees C. The Q10 was 3.07 between 20 and 30 degrees C whereas between 30 to 40 degrees C it was 3.31. Only phosphorylated compounds caused significant inhibition of enzyme activity. They included ADP, FDP, F6P, G6P, PEP, 6PG, 2-PGA, R1P, R5P, and Ru5p.", "contents": "Properties and regulation of ribulose diphosphate carboxylase from Thiobacillus novellus. Ribulose-diphosphate carboxylase from Thiobacillus novellus has been purified to hemogeneity as observed by polyacrylamide gel electrophoresis and U.V. light observation during sedimentation velocity analysis. The optimum pH for the enzyme with Tris-HCl buffers was about 8.2. Concentrations of this buffer in excess of 80 mM were inhibitory. The apparent Km for RuDP was about 14.8 muM with a Hill value of 1.5, for HCO3- the apparent Km was about 11.7 mM with an n value of 1.18 and for Mg2+ about 0.61 mM. The enzyme was specific for this cation. Relatively high concentrations of either Hg2+ or pCMB were required before significant inhibition was observed. Activity declined slowly during a 4-hr incubation period in either 3.0 M or 8.0 M urea. Incubation for 12 hrs resulted in complete loss of activity which was not prevented by 10 mM Mg2+ and was not reversed by dialysis and subsequent addition of 10 mM cysteine. Polyacrylamide gel electrophoresis revealed a loss of the major band and the appearance of 2 new bands. SDS polyacrylamide gel electrophoresis gave an average M.W. of 73500 +/- 2500 for the slower moving band and 12250 +/- 2500 for the faster moving. However, incubation in urea for up to 40 hrs revealed a decrease in the M.W. of the slower moving band to about 60000. The Ea for the enzyme was calculated to be about 18.85 kcal mole-1, with the possibility of a \"break\" between 40 and 50 degrees C. The Q10 was 3.07 between 20 and 30 degrees C whereas between 30 to 40 degrees C it was 3.31. Only phosphorylated compounds caused significant inhibition of enzyme activity. They included ADP, FDP, F6P, G6P, PEP, 6PG, 2-PGA, R1P, R5P, and Ru5p."}
{"id": "PMID:242295", "title": "Effect of cyclic AMP on catabolite repressed bacterial sporogenesis of an anaerobe.", "content": "The sporulation of a high frequency sporogenic mutant of Clostridium botulinum was reduced to less than 30% in a medium containing 270 mM glucose. The repression was reversed from 30 to greater than 80% sporulation by the addition of 10(-5) or 10(-4) M cyclic 3',5'-adenosine monophosphate (cAMP) or monobutyrul cyclic AMP (B-cAMP). No difference was observed in amount of growth with the addition of either the cAMP or B-cAMP. Glucose consumption was enhanced by the addition of either of the cyclic nucleotides and corresponding changes in pH were observed. The catabolite repression by glucose was reversed by ATP or ADP. Except for GTP, guanine nucleotides were not effective. The intracellular cyclic AMP levels were high in vegetative, sporulating and derepressed cells, but low in glucose-repressed cells. The findings suggest that the sporulation of the anaerobe was sensitive to catabolite repression which was specifically reversed by cyclic AMP.", "contents": "Effect of cyclic AMP on catabolite repressed bacterial sporogenesis of an anaerobe. The sporulation of a high frequency sporogenic mutant of Clostridium botulinum was reduced to less than 30% in a medium containing 270 mM glucose. The repression was reversed from 30 to greater than 80% sporulation by the addition of 10(-5) or 10(-4) M cyclic 3',5'-adenosine monophosphate (cAMP) or monobutyrul cyclic AMP (B-cAMP). No difference was observed in amount of growth with the addition of either the cAMP or B-cAMP. Glucose consumption was enhanced by the addition of either of the cyclic nucleotides and corresponding changes in pH were observed. The catabolite repression by glucose was reversed by ATP or ADP. Except for GTP, guanine nucleotides were not effective. The intracellular cyclic AMP levels were high in vegetative, sporulating and derepressed cells, but low in glucose-repressed cells. The findings suggest that the sporulation of the anaerobe was sensitive to catabolite repression which was specifically reversed by cyclic AMP."}
{"id": "PMID:242296", "title": "The isolation and characterization of peroxisomes (microbodies) from baker's yeast, Saccharomyces cerevisiae.", "content": "Peroxisomes were isolated form derepressed (lactose grown) Saccharomyces cerevisiae cells following homogenization with a \"Merkenschlager\" cell mill (at 0 degrees C using glass beads). Catalase and urate oxidase, along with low activities of D-amino acid oxidase and L-alpha-hydroxyacid oxidase (glycollate oxidase), were associated with the peroxisomes. No catalase activity was present in glucose repressed cells. When protoplasts prepared from derepressed cells were used for peroxisome isolation, catalase activity was not sedimentable through gradients. Apparently peroxisomes were destroyed as the cells became fermentative during protoplast preparation. The distribution of glyoxylate cycle enzymes was examined. Isocitrate lyase was not sedimentable, suggesting that, if the enzyme is peroxisome-associated, it is either readily released of present in a labile second class of peroxisomes. Low activities of malate dehydrogenase and citrate synthetase were found in peroxisome fractions from gradients, but may represent mitochondrial contamination. Citrate synthetase was not found associated with a low-density particle as had been previously reported.", "contents": "The isolation and characterization of peroxisomes (microbodies) from baker's yeast, Saccharomyces cerevisiae. Peroxisomes were isolated form derepressed (lactose grown) Saccharomyces cerevisiae cells following homogenization with a \"Merkenschlager\" cell mill (at 0 degrees C using glass beads). Catalase and urate oxidase, along with low activities of D-amino acid oxidase and L-alpha-hydroxyacid oxidase (glycollate oxidase), were associated with the peroxisomes. No catalase activity was present in glucose repressed cells. When protoplasts prepared from derepressed cells were used for peroxisome isolation, catalase activity was not sedimentable through gradients. Apparently peroxisomes were destroyed as the cells became fermentative during protoplast preparation. The distribution of glyoxylate cycle enzymes was examined. Isocitrate lyase was not sedimentable, suggesting that, if the enzyme is peroxisome-associated, it is either readily released of present in a labile second class of peroxisomes. Low activities of malate dehydrogenase and citrate synthetase were found in peroxisome fractions from gradients, but may represent mitochondrial contamination. Citrate synthetase was not found associated with a low-density particle as had been previously reported."}
{"id": "PMID:242297", "title": "Conditions for induced fusion of fungal protoplasts in polyethylene glycol solutions.", "content": "Solutions containing polyethylene glycol MW 6000 (PEG) induced fusion of protoplasts of Penicillium chrysogenum. Balanced heterokaryons were formed by fusion of nutritionally complementing protoplasts. Heterokaryotic fusion products were obtained up to a frequency of 4% of the number of protoplasts, surviving the fusion treatment. Investigation of the conditions, necessary to achieve this high fusion frequency, showed that supplementing the PEG solution with Ca++ and adjustment to high pH gave the best results. Mechanisms of fusion of fungal protoplasts by PEG, calcium and alkaline pH are discussed in view of the obtained results.", "contents": "Conditions for induced fusion of fungal protoplasts in polyethylene glycol solutions. Solutions containing polyethylene glycol MW 6000 (PEG) induced fusion of protoplasts of Penicillium chrysogenum. Balanced heterokaryons were formed by fusion of nutritionally complementing protoplasts. Heterokaryotic fusion products were obtained up to a frequency of 4% of the number of protoplasts, surviving the fusion treatment. Investigation of the conditions, necessary to achieve this high fusion frequency, showed that supplementing the PEG solution with Ca++ and adjustment to high pH gave the best results. Mechanisms of fusion of fungal protoplasts by PEG, calcium and alkaline pH are discussed in view of the obtained results."}
{"id": "PMID:242298", "title": "Catabolism of D-fructose and D-ribose by Pseudomonas doudoroffii. II. Properties of 1-phosphofructokinase and 6-phosphofructokinase.", "content": "1. The 1-P-fructokinase (1-PFK) and 6-P-fructokinase (6-PFK) from Pseudmonas doudoroffii were partially purified by a combination of (NH4)2SO4 fractionation and DEAE-Sephadex column chromatography. The pH optima of these enzymes were 9.0 and 8.5, respectively. 2. When the concentrations of the substrates of the 1-PFK reaction were varied, Michaelis-Menten kinetics were observed. The Kms for D-fructose-1-P (F-1-P) and ATP were 3.03 X 10(-4) M and 3.39 X 10(-4) M, respectively. Variation of MgCl2 at fixed concentrations of F-1-P and ATP resulted in sigmoidal kinetics; about 10 mM MgCl2 was necessary for maximal activity. Activity of 1-PFK was inhibited when the ratio of ATP:Mg++ was higher than 0.5, suggesting that ATP:2Mg++ was the substrate and that free ATP was inhibitory. Although an absolute requirement for K+ or NH4+ could not be demonstrated, these cations stimulated the rate of the reaction. Activity of 1-PFK was not significantly affected by 3 mM AMP, cyclic-AMP, Pi, D-fructose-6-P (F-6-P), ADP, P-enolpyruvate (PEP), pyruvate, citrate, or L-gluamate. 3. Sigmoidal kinetics were observed for 6-PFK when the concentration of F-6-P was increased and the level of ATP was kept constant. Activity of 6-PFK was increased by ADP, inhibited by PEP, and unaffected by 3 mM AMP, cyclic-AMP, Pi, F-1-P, pyruvate, or citrate.", "contents": "Catabolism of D-fructose and D-ribose by Pseudomonas doudoroffii. II. Properties of 1-phosphofructokinase and 6-phosphofructokinase. 1. The 1-P-fructokinase (1-PFK) and 6-P-fructokinase (6-PFK) from Pseudmonas doudoroffii were partially purified by a combination of (NH4)2SO4 fractionation and DEAE-Sephadex column chromatography. The pH optima of these enzymes were 9.0 and 8.5, respectively. 2. When the concentrations of the substrates of the 1-PFK reaction were varied, Michaelis-Menten kinetics were observed. The Kms for D-fructose-1-P (F-1-P) and ATP were 3.03 X 10(-4) M and 3.39 X 10(-4) M, respectively. Variation of MgCl2 at fixed concentrations of F-1-P and ATP resulted in sigmoidal kinetics; about 10 mM MgCl2 was necessary for maximal activity. Activity of 1-PFK was inhibited when the ratio of ATP:Mg++ was higher than 0.5, suggesting that ATP:2Mg++ was the substrate and that free ATP was inhibitory. Although an absolute requirement for K+ or NH4+ could not be demonstrated, these cations stimulated the rate of the reaction. Activity of 1-PFK was not significantly affected by 3 mM AMP, cyclic-AMP, Pi, D-fructose-6-P (F-6-P), ADP, P-enolpyruvate (PEP), pyruvate, citrate, or L-gluamate. 3. Sigmoidal kinetics were observed for 6-PFK when the concentration of F-6-P was increased and the level of ATP was kept constant. Activity of 6-PFK was increased by ADP, inhibited by PEP, and unaffected by 3 mM AMP, cyclic-AMP, Pi, F-1-P, pyruvate, or citrate."}
{"id": "PMID:242299", "title": "Purification and properties of thiosulfate reductase from Desulfovibrio gigas.", "content": "Thiosulfate reductase of the dissimilatory sulfate-reducing bacterium Desulfovibrio gigas has been purified 415-fold and its properties investigated. The enzyme was unstable during the different steps of purification as well as during storage at - 15 degrees C. The molecular weight of thiosulfate reductase estimated from the chromatographic behaviour of the enzyme on Sephadex G-200 was close to 220000. The absorption spectrum of the purified enzyme exhibited a protein peak at 278 nm without characteristic features in the visible region. Thiosulfate reductase catalyzed the stoichiometric production of hydrogen sulfide and sulfite from thiosulfate, and exhibited tetrathionate reductase activity. It did not show sulfite reductase activity. The optimum pH of thiosulfate reduction occurred between pH 7.4 and 8.0 and its Km value for thiosulfate was calculated to be 5 - 10(-4)M. The sensitivity of thiosulfate reductase to sulfhydryl reagent and the reversal of the inhibition by cysteine indicated that one or more sulfhydryl groups were involved in the catalytic activity. The study of electron transport between hydrogenase and thiosulfate reductase showed that the most efficient coupling was obtained with a system containing cytochromes c3 (Mr = 13000) and c3 (Mr = 26000).", "contents": "Purification and properties of thiosulfate reductase from Desulfovibrio gigas. Thiosulfate reductase of the dissimilatory sulfate-reducing bacterium Desulfovibrio gigas has been purified 415-fold and its properties investigated. The enzyme was unstable during the different steps of purification as well as during storage at - 15 degrees C. The molecular weight of thiosulfate reductase estimated from the chromatographic behaviour of the enzyme on Sephadex G-200 was close to 220000. The absorption spectrum of the purified enzyme exhibited a protein peak at 278 nm without characteristic features in the visible region. Thiosulfate reductase catalyzed the stoichiometric production of hydrogen sulfide and sulfite from thiosulfate, and exhibited tetrathionate reductase activity. It did not show sulfite reductase activity. The optimum pH of thiosulfate reduction occurred between pH 7.4 and 8.0 and its Km value for thiosulfate was calculated to be 5 - 10(-4)M. The sensitivity of thiosulfate reductase to sulfhydryl reagent and the reversal of the inhibition by cysteine indicated that one or more sulfhydryl groups were involved in the catalytic activity. The study of electron transport between hydrogenase and thiosulfate reductase showed that the most efficient coupling was obtained with a system containing cytochromes c3 (Mr = 13000) and c3 (Mr = 26000)."}
{"id": "PMID:242300", "title": "Purification and properties of a fructose-1,6-diphosphate activated L-lactate dehydrogenase from Staphylococcus epidermidis.", "content": "L-(+)-lactate dehydrogenase (LDH) from Staphylococcus epidermidis ATCC 14990 was purified by affinity chromatography. The purified enzyme was specifically activated by fructose-1,6-diphosphate (FDP). The concentration of FDP required for 50% maximal activity was about 0.15 mM. The enzyme activity was inhibited by adenosine diphosphate (ADP) and oxamate. The inhibition by ADP appeared to be competitive with respect to reduced nicotinamide adenine dinucleotide (NADH). The catalytic activity of the LDH for pyruvate reduction exhibited an optimum at pH 5.6. The enzyme is composed of four, probably identical, subunits. Sephadex gel filtration and sedimentation velocity at pH 5.6 Yielded molecular weights of about 130 000 and 126 000, respectively. The molecular weight at pH 6.5 and 7.0 was found to be only about 68 000. Polyacrylamide gel electrophoresis in the presence of sodium dodecylsulfate and sedimentation velocity at pH 2.0 or 8.5 revealed monomeric subunits with an approximate molecular weight of 36000. The thermostability of the heat labile enzyme was increased in the presence of FDP, NADH and pyruvate. The purified LDH exhibited an anomalous type of kinetic behavior. Plots of initial velocity vs. different concentrations of pyruvate, NADH or FDP led to saturation curves with intermediary plateau regions. As a consequence of these plateau regions the Hill coefficient alternated between lower and higher n-values. Some distinguishing properties of the S. epidermidis LDH and other LDHs activated by FDP are discussed.", "contents": "Purification and properties of a fructose-1,6-diphosphate activated L-lactate dehydrogenase from Staphylococcus epidermidis. L-(+)-lactate dehydrogenase (LDH) from Staphylococcus epidermidis ATCC 14990 was purified by affinity chromatography. The purified enzyme was specifically activated by fructose-1,6-diphosphate (FDP). The concentration of FDP required for 50% maximal activity was about 0.15 mM. The enzyme activity was inhibited by adenosine diphosphate (ADP) and oxamate. The inhibition by ADP appeared to be competitive with respect to reduced nicotinamide adenine dinucleotide (NADH). The catalytic activity of the LDH for pyruvate reduction exhibited an optimum at pH 5.6. The enzyme is composed of four, probably identical, subunits. Sephadex gel filtration and sedimentation velocity at pH 5.6 Yielded molecular weights of about 130 000 and 126 000, respectively. The molecular weight at pH 6.5 and 7.0 was found to be only about 68 000. Polyacrylamide gel electrophoresis in the presence of sodium dodecylsulfate and sedimentation velocity at pH 2.0 or 8.5 revealed monomeric subunits with an approximate molecular weight of 36000. The thermostability of the heat labile enzyme was increased in the presence of FDP, NADH and pyruvate. The purified LDH exhibited an anomalous type of kinetic behavior. Plots of initial velocity vs. different concentrations of pyruvate, NADH or FDP led to saturation curves with intermediary plateau regions. As a consequence of these plateau regions the Hill coefficient alternated between lower and higher n-values. Some distinguishing properties of the S. epidermidis LDH and other LDHs activated by FDP are discussed."}
{"id": "PMID:242301", "title": "Polybase induced lysis of yeast spheroplasts. A new gentle method for preparation of vacuoles.", "content": "The polybasic macromolecules DEAE-dextran (diethylaminoethyl-dextran, molecular weight 500000) and poly-DL-lysine (molecular weight 30000-70000) were absorbed with a high affinity by spheroplasts of Candida utilis and subsequently, induced lysis. The extent of lysis of spheroplasts and of the liberated vacuoles was studied under various conditions using alpha-glucosidase activity and soluble arginine as cytoplasmic and vacuolar markers, respectively. Adsorption of polybases was rapidly completed even at 0 degrees C; however, with small doses, lysis was poor at 0-12 degrees C and extensive at temperatures above 12 degrees C. This permitted the completion of adsorption before initiating lysis. The purified vacuoles were also sensitive to polybases though less so than the spheroplasts; however, after lysis of spheroplasts the liberated vacuoles were well protected against the action of polybases. A treatment with polybases which disrupted more than 99% of the spheroplasts left at least 70% of the vacuoles intact. Potassium chloride in high concentrations and calcium chloride in low concentrations inhibited polybase induced lysis of spheroplasts by preventing or even reversing the polybase adsorption. A polyacidic macromolecule, dextran sulfate, could prevent but not reverse the adsorption of polybase and subsequent lysis. Metabolic inhibitors reduced the susceptibility of spheroplasts to polybase induced lysis. Vacuoles isolated from polybase lysed spheroplasts still contained large pools of soluble amino acids, and their ability to transport arginine specifically is a further indication of their functional integrity.", "contents": "Polybase induced lysis of yeast spheroplasts. A new gentle method for preparation of vacuoles. The polybasic macromolecules DEAE-dextran (diethylaminoethyl-dextran, molecular weight 500000) and poly-DL-lysine (molecular weight 30000-70000) were absorbed with a high affinity by spheroplasts of Candida utilis and subsequently, induced lysis. The extent of lysis of spheroplasts and of the liberated vacuoles was studied under various conditions using alpha-glucosidase activity and soluble arginine as cytoplasmic and vacuolar markers, respectively. Adsorption of polybases was rapidly completed even at 0 degrees C; however, with small doses, lysis was poor at 0-12 degrees C and extensive at temperatures above 12 degrees C. This permitted the completion of adsorption before initiating lysis. The purified vacuoles were also sensitive to polybases though less so than the spheroplasts; however, after lysis of spheroplasts the liberated vacuoles were well protected against the action of polybases. A treatment with polybases which disrupted more than 99% of the spheroplasts left at least 70% of the vacuoles intact. Potassium chloride in high concentrations and calcium chloride in low concentrations inhibited polybase induced lysis of spheroplasts by preventing or even reversing the polybase adsorption. A polyacidic macromolecule, dextran sulfate, could prevent but not reverse the adsorption of polybase and subsequent lysis. Metabolic inhibitors reduced the susceptibility of spheroplasts to polybase induced lysis. Vacuoles isolated from polybase lysed spheroplasts still contained large pools of soluble amino acids, and their ability to transport arginine specifically is a further indication of their functional integrity."}
{"id": "PMID:242302", "title": "Systematic desensitization of erectile impotence: a controlled study.", "content": "Results of a study conducted to assess the therapeutic effectiveness of systematic desensitization of erectile impotence are described. Three groups of eight patients each were formed. They were treated with systematic desensitization or conventional medication and general advice, or put on a waiting list. Therapeutic effects were investigated on the behavioral, subjective, and physiological levels. There were no significant differences among the three groups except on the subjective level. On this level, after therapy the systematic desensitization group rated feelings in sexually arousing situations as associated with significantly less anxiety than the other two groups. Systematic desensitization used alone as a treatment for erectile impotence shows only limited therapeutic effect. The unimproved patients were later treated using a modification of the Masters and Johnson technique. Early results suggest that this technique may be superior to systematic desensitization alone.", "contents": "Systematic desensitization of erectile impotence: a controlled study. Results of a study conducted to assess the therapeutic effectiveness of systematic desensitization of erectile impotence are described. Three groups of eight patients each were formed. They were treated with systematic desensitization or conventional medication and general advice, or put on a waiting list. Therapeutic effects were investigated on the behavioral, subjective, and physiological levels. There were no significant differences among the three groups except on the subjective level. On this level, after therapy the systematic desensitization group rated feelings in sexually arousing situations as associated with significantly less anxiety than the other two groups. Systematic desensitization used alone as a treatment for erectile impotence shows only limited therapeutic effect. The unimproved patients were later treated using a modification of the Masters and Johnson technique. Early results suggest that this technique may be superior to systematic desensitization alone."}
{"id": "PMID:242311", "title": "The human leukocyte photoreactivating enzyme.", "content": "A photoreactivating enzyme from human leukocytes has been isolated and characterized. The enzyme requires DNA irradiated with ultraviolet light (220-300 nm) as substrate, and visible light (300-600 nm) for catalysis. In the reaction, the enzyme converts cyclobutyl pyrimidine dimers in the DNA to monomer pyrimidines. The enzyme has an apparent monomer molecular weight of 40,000 and tends to form aggregates. The pH optimum of 7.2 and absence of a requirement for metal ions are similar to the requirements of the Escherichia coli enzyme; however, the ionic strength optimum of 0.05 is much lower than those for other photoreactivating enzymes. The demonstration that human cells possess photoreactivating enzyme implies that a direct test by photoreactivation may be made of the role of pyrimidine dimers in the induction of abnormal cell growth.", "contents": "The human leukocyte photoreactivating enzyme. A photoreactivating enzyme from human leukocytes has been isolated and characterized. The enzyme requires DNA irradiated with ultraviolet light (220-300 nm) as substrate, and visible light (300-600 nm) for catalysis. In the reaction, the enzyme converts cyclobutyl pyrimidine dimers in the DNA to monomer pyrimidines. The enzyme has an apparent monomer molecular weight of 40,000 and tends to form aggregates. The pH optimum of 7.2 and absence of a requirement for metal ions are similar to the requirements of the Escherichia coli enzyme; however, the ionic strength optimum of 0.05 is much lower than those for other photoreactivating enzymes. The demonstration that human cells possess photoreactivating enzyme implies that a direct test by photoreactivation may be made of the role of pyrimidine dimers in the induction of abnormal cell growth."}
{"id": "PMID:242312", "title": "Endonuclease III: an endonuclease from Escherichia coli that introduces single polynucleotide chain scissions in ultraviolet-irradiated DNA.", "content": "An endonuclease that makes single polynucleotide chain scissions in UV-irradiated DNA has been purified from Escherichia coli. The activity has the following properties: (1) unirradiated DNA is attacked very little if at all; (2) single-stranded DNA is not attacked, whether irradiated or not; (3) there is no requirement for divalent cations, and the activity is not affected by addition of EDTA; (4) the pH optimum is approximately 7; (5) the activity is inhibited by 1 M NaCl, single-stranded DNA, transfer RNA, and unirradiated double-stranded DNA; (6) the sedimentation coefficient, S20, W, is approximately 2.6; (7) it is a basic protein. The enzyme is tentatively named E. coli endonuclease III. The physiological function of the endonuclease has not yet been established.", "contents": "Endonuclease III: an endonuclease from Escherichia coli that introduces single polynucleotide chain scissions in ultraviolet-irradiated DNA. An endonuclease that makes single polynucleotide chain scissions in UV-irradiated DNA has been purified from Escherichia coli. The activity has the following properties: (1) unirradiated DNA is attacked very little if at all; (2) single-stranded DNA is not attacked, whether irradiated or not; (3) there is no requirement for divalent cations, and the activity is not affected by addition of EDTA; (4) the pH optimum is approximately 7; (5) the activity is inhibited by 1 M NaCl, single-stranded DNA, transfer RNA, and unirradiated double-stranded DNA; (6) the sedimentation coefficient, S20, W, is approximately 2.6; (7) it is a basic protein. The enzyme is tentatively named E. coli endonuclease III. The physiological function of the endonuclease has not yet been established."}
{"id": "PMID:242313", "title": "Two temperature-sensitive polA mutants: an approach to the role in vivo of  DNA polymerase I.", "content": "DNA polymerase I (Pol I) purified from a strain carrying polA12 demonstrates a defect primarily in the polymerase portion of the molecule. The mutant enzyme is altered in its structure and template specificity. Pol I isolated from strains carrying polAexl are primarily defective in 5' in equilibrium 3' exonuclease. The polAexl lesion renders strains conditonally lethal.", "contents": "Two temperature-sensitive polA mutants: an approach to the role in vivo of  DNA polymerase I. DNA polymerase I (Pol I) purified from a strain carrying polA12 demonstrates a defect primarily in the polymerase portion of the molecule. The mutant enzyme is altered in its structure and template specificity. Pol I isolated from strains carrying polAexl are primarily defective in 5' in equilibrium 3' exonuclease. The polAexl lesion renders strains conditonally lethal."}
{"id": "PMID:242317", "title": "Purification of normal human urinary N-acetyl-beta-hexosaminidase A by affinity chromatography.", "content": "N-Acetyl-beta-hexosaminidase A was purified 1000-fold from human urine by chromatography on DEAE-Sephadex followed by concanavalin A--Sepharose affinity chromatography. The optimal pH range was 4.4--4.5 for both the N-acetylglucosamine and N-acetylgalactosamine derivatives. The Km values were 0.51 mM and 0.28 mM respectively for the N-acetylglucosamine and N-acetylgalactosamine derivatives. The glycoprotein nature of the urinary enzyme was established by its affinity towards concanavalin A as well as by the presence of sialic acid, galactose, glucose, mannose and hexosamines in the molecule.", "contents": "Purification of normal human urinary N-acetyl-beta-hexosaminidase A by affinity chromatography. N-Acetyl-beta-hexosaminidase A was purified 1000-fold from human urine by chromatography on DEAE-Sephadex followed by concanavalin A--Sepharose affinity chromatography. The optimal pH range was 4.4--4.5 for both the N-acetylglucosamine and N-acetylgalactosamine derivatives. The Km values were 0.51 mM and 0.28 mM respectively for the N-acetylglucosamine and N-acetylgalactosamine derivatives. The glycoprotein nature of the urinary enzyme was established by its affinity towards concanavalin A as well as by the presence of sialic acid, galactose, glucose, mannose and hexosamines in the molecule."}
{"id": "PMID:242318", "title": "Properties of follicle-stimulating-hormone receptor in cell membranes of bovine testis.", "content": "A simple method for preparing plasma membranes from bovine testes is described. Bovine testicular receptor has a high affinity and specificity for 125I-labelled human FSH (follicle-stimulating hormone). The specific binding of 125I-labelled human FSH to the plasma membranes is a saturable process with respect to the amounts of receptor protein and FSH added. The association and dissociation of 125I-labelled human FSH are time- and temperature-dependent, and the binding of labelled human FSH to bovine testicular receptor is strong and not readily reversible. Scatchard [Ann. N.Y. Acad. Sci. (1949) 51, 660-672] analysis indicates a dissociation constant, Kd, of 9.8 X10(-11)M, and 5.9 X 10(-14)mol of binding sites/mg of membrane protein. The testicular membrane receptor is heat-labile. Preheating at 40 degrees C for 15 min destroyed 30% of the binding activity. Specific binding is pH-dependent, with an optimum between pH 7.0 and 7.5. Brief exposure to extremes of pH caused irreversible damage to the receptors. The ionic strength of the incubation medium markedly affects the association of 125I-labelled human FSH with its testicular receptor. Various cations at concentrations of 0.1M inhibit almost completely the binding of 125I-labelled human FSH. Nuclectides and steroid hormones at concentrations of 1mM and 5mu/ml respectively have no effect on the binding of FSH to its receptor. Incubation of membranes with and chymotrypsin resulted in an almost complete loss of binding activity, suggesting that protein moieties are essential for the binding of 125I-labelled human FSH. Binding of 125I-labelled human FSH to bovine testicular receptor does not result in destruction or degradation of the hormone.", "contents": "Properties of follicle-stimulating-hormone receptor in cell membranes of bovine testis. A simple method for preparing plasma membranes from bovine testes is described. Bovine testicular receptor has a high affinity and specificity for 125I-labelled human FSH (follicle-stimulating hormone). The specific binding of 125I-labelled human FSH to the plasma membranes is a saturable process with respect to the amounts of receptor protein and FSH added. The association and dissociation of 125I-labelled human FSH are time- and temperature-dependent, and the binding of labelled human FSH to bovine testicular receptor is strong and not readily reversible. Scatchard [Ann. N.Y. Acad. Sci. (1949) 51, 660-672] analysis indicates a dissociation constant, Kd, of 9.8 X10(-11)M, and 5.9 X 10(-14)mol of binding sites/mg of membrane protein. The testicular membrane receptor is heat-labile. Preheating at 40 degrees C for 15 min destroyed 30% of the binding activity. Specific binding is pH-dependent, with an optimum between pH 7.0 and 7.5. Brief exposure to extremes of pH caused irreversible damage to the receptors. The ionic strength of the incubation medium markedly affects the association of 125I-labelled human FSH with its testicular receptor. Various cations at concentrations of 0.1M inhibit almost completely the binding of 125I-labelled human FSH. Nuclectides and steroid hormones at concentrations of 1mM and 5mu/ml respectively have no effect on the binding of FSH to its receptor. Incubation of membranes with and chymotrypsin resulted in an almost complete loss of binding activity, suggesting that protein moieties are essential for the binding of 125I-labelled human FSH. Binding of 125I-labelled human FSH to bovine testicular receptor does not result in destruction or degradation of the hormone."}
{"id": "PMID:242319", "title": "Physicochemical properties of two atypical cytochromes c, Crithidia cytochrome c-557 and Euglena cytochrome c-558.", "content": "Cytochrome c-557 from Crithidia oncopelti and cytochrome c-558 from Euglena gracilis are mitochondrial cytochromes c that have an atypical haem-binding site. It was of interest to know whether the loss of one thioether bond affected the physicochemical properties of these cytochromes. The thermodynamic parameters of the redox potential were measured. The reaction with imidazole, the kinetics and thermodynamics of the alkaline isomerization and the effect of heating on the visible spectrum are described for the ferricytochromes. The kinetics of the loss of cyanide, the spectral changes occurring on reduction with dithionite at alkaline pH values and the reactivity with CO are described for the ferrocytochromes. In many respects the cytochromes of the two protozoans are very similar to the cytochromes of horse and yeast. The ferricytochromes do, however, undergo a reversible transition to high-spin species on heating, which may be due to the more flexible attachment of the prosthetic group. Similarly the alkaline isomers of cytochromes c-557 and c-558 give rise to high-spin proteins above pH 11. The alkaline isomerization of cytochrome c-558, involves a pKobs. of 10 and kinetics which do not obey the model of Davis et al. [(1974) J. Biol. Chem. 249, 2624-2632] for horse cytochrome c. It is proposed that a model involving two ionizations, followed by a conformation change, may fit the data. Both cytochromes c-557 and c-558 combine slowly with CO at neutral pH values.", "contents": "Physicochemical properties of two atypical cytochromes c, Crithidia cytochrome c-557 and Euglena cytochrome c-558. Cytochrome c-557 from Crithidia oncopelti and cytochrome c-558 from Euglena gracilis are mitochondrial cytochromes c that have an atypical haem-binding site. It was of interest to know whether the loss of one thioether bond affected the physicochemical properties of these cytochromes. The thermodynamic parameters of the redox potential were measured. The reaction with imidazole, the kinetics and thermodynamics of the alkaline isomerization and the effect of heating on the visible spectrum are described for the ferricytochromes. The kinetics of the loss of cyanide, the spectral changes occurring on reduction with dithionite at alkaline pH values and the reactivity with CO are described for the ferrocytochromes. In many respects the cytochromes of the two protozoans are very similar to the cytochromes of horse and yeast. The ferricytochromes do, however, undergo a reversible transition to high-spin species on heating, which may be due to the more flexible attachment of the prosthetic group. Similarly the alkaline isomers of cytochromes c-557 and c-558 give rise to high-spin proteins above pH 11. The alkaline isomerization of cytochrome c-558, involves a pKobs. of 10 and kinetics which do not obey the model of Davis et al. [(1974) J. Biol. Chem. 249, 2624-2632] for horse cytochrome c. It is proposed that a model involving two ionizations, followed by a conformation change, may fit the data. Both cytochromes c-557 and c-558 combine slowly with CO at neutral pH values."}
{"id": "PMID:242320", "title": "Kinetic studies on mammalian cytochrome c modified with 2-hydroxy-5-hydroxy-5-nitrobenzyl bromide.", "content": "The reduction of 2-hydroxy-5-nitrobenzyl tryptophyl cytochrome c by the chromous ion was studied by stopped-flow techniques. At pH6.5 the reduction of 2-hydroxy-5-nitrobenzyl tryptophyl cytochrome c is complex, showing the presence of three distinct phases. Two chromium concentration-dependent phases are observed (1.1 X 10(5) M-1-S-1, phase 1; 1.25 X 10(4)M-1-S-1, phase 2) and one slow first-order process (0.25S-1, phase 3). A comparison of the static and kinetic difference spectra, along with the data from the reduction of the reoxidized reduced protein, suggests that the slow chromium concentration-independent phase is due to a slow conformational event after fast reduction of the NO2 group. The rates of the chromium concentration-dependent phases show a marked variation with pH above 7.5. The activation energies for the three processes were also measured at 33.2, 38.6 and 69.7 kJ-mol-1 for phases 1, 2 and 3 respectively. The reaction of reduced 2-hydroxy-5-nitrobenzyl tryptophyl cytochrome c with CO was foollowed by means of both stopped-flow and flash photolysis. The combination with CO at pH 6.8 as measured in stopped-flow experiments showed two phases, one CO-dependent phase (phase 2, 2.4 X 10(2)M-1-S-1) and one CO-independent phase (phase 1, 0.015S-1). Investigation of the pH-dependence of the phases showed both the rates and amounts of each phase to be pH-invariant. CO recombination, after photolytic removal, was found to be biphasic; a CO-dependent phase (phase 2, 2.4 X 10(2)M-1-S-1) and a CO-independent phase (phase 1, 1.0s-1) were observed. A tentative model which can accommodate these observations is proposed.", "contents": "Kinetic studies on mammalian cytochrome c modified with 2-hydroxy-5-hydroxy-5-nitrobenzyl bromide. The reduction of 2-hydroxy-5-nitrobenzyl tryptophyl cytochrome c by the chromous ion was studied by stopped-flow techniques. At pH6.5 the reduction of 2-hydroxy-5-nitrobenzyl tryptophyl cytochrome c is complex, showing the presence of three distinct phases. Two chromium concentration-dependent phases are observed (1.1 X 10(5) M-1-S-1, phase 1; 1.25 X 10(4)M-1-S-1, phase 2) and one slow first-order process (0.25S-1, phase 3). A comparison of the static and kinetic difference spectra, along with the data from the reduction of the reoxidized reduced protein, suggests that the slow chromium concentration-independent phase is due to a slow conformational event after fast reduction of the NO2 group. The rates of the chromium concentration-dependent phases show a marked variation with pH above 7.5. The activation energies for the three processes were also measured at 33.2, 38.6 and 69.7 kJ-mol-1 for phases 1, 2 and 3 respectively. The reaction of reduced 2-hydroxy-5-nitrobenzyl tryptophyl cytochrome c with CO was foollowed by means of both stopped-flow and flash photolysis. The combination with CO at pH 6.8 as measured in stopped-flow experiments showed two phases, one CO-dependent phase (phase 2, 2.4 X 10(2)M-1-S-1) and one CO-independent phase (phase 1, 0.015S-1). Investigation of the pH-dependence of the phases showed both the rates and amounts of each phase to be pH-invariant. CO recombination, after photolytic removal, was found to be biphasic; a CO-dependent phase (phase 2, 2.4 X 10(2)M-1-S-1) and a CO-independent phase (phase 1, 1.0s-1) were observed. A tentative model which can accommodate these observations is proposed."}
{"id": "PMID:242321", "title": "The purification and properties of peroxidase in Mycobacterium tuberculosis H37Rv and its possible role in the mechanism of action of isonicotinic acid hydrazide.", "content": "Peroxidase from Mycobacterium tuberculosis H37Rv was purified to homogeneity. The homogeneous protein exhibits catalase and Y (Youatt's)-enzyme activities in addition to peroxidase activity. Further confirmation that the three activities are due to a single enzyme was accomplished by other criteria, such as differential thermal inactivation, sensitivity to different inhibitors, and co-purification. The Y enzyme (peroxidase) was separated from NADase (NAD+ glycohydrolase) inhibitor by gel filtration on Sephadex G-200. The molecular weights of peroxidase and NADase inhibitor, as determined by gel filtration, are 240000 and 98000 respectively. The Y enzyme shows two Km values for both isoniazid (isonicotinic acid hydrazide) and NAD at low and high concentrations. Analysis of the data by Hill plots revealed that the enzyme has one binding site at lower substrate concentrations and more than one at higher substrate concentration. The enzyme contains 6g-atoms of iron/mol. Highly purified preparations of peroxidases from different sources catalyse the Y-enzyme reaction, suggesting that the nature of the reaction may be a peroxidatic oxidation of isoniazid. Moreover, the Y-enzyme reaction is enhanced by O2. Isoniazid-resistant mutants do not exhibit Y-enzyme, peroxidase or catalase activities, and do not take up isoniazid. The Y-enzyme reaction is therefore implicated in the uptake of the drug.", "contents": "The purification and properties of peroxidase in Mycobacterium tuberculosis H37Rv and its possible role in the mechanism of action of isonicotinic acid hydrazide. Peroxidase from Mycobacterium tuberculosis H37Rv was purified to homogeneity. The homogeneous protein exhibits catalase and Y (Youatt's)-enzyme activities in addition to peroxidase activity. Further confirmation that the three activities are due to a single enzyme was accomplished by other criteria, such as differential thermal inactivation, sensitivity to different inhibitors, and co-purification. The Y enzyme (peroxidase) was separated from NADase (NAD+ glycohydrolase) inhibitor by gel filtration on Sephadex G-200. The molecular weights of peroxidase and NADase inhibitor, as determined by gel filtration, are 240000 and 98000 respectively. The Y enzyme shows two Km values for both isoniazid (isonicotinic acid hydrazide) and NAD at low and high concentrations. Analysis of the data by Hill plots revealed that the enzyme has one binding site at lower substrate concentrations and more than one at higher substrate concentration. The enzyme contains 6g-atoms of iron/mol. Highly purified preparations of peroxidases from different sources catalyse the Y-enzyme reaction, suggesting that the nature of the reaction may be a peroxidatic oxidation of isoniazid. Moreover, the Y-enzyme reaction is enhanced by O2. Isoniazid-resistant mutants do not exhibit Y-enzyme, peroxidase or catalase activities, and do not take up isoniazid. The Y-enzyme reaction is therefore implicated in the uptake of the drug."}
{"id": "PMID:242322", "title": "A comparison of the activity of phosphatidylinositol phosphodiesterase against substrate in dispersions and as monolayers at the air-water interface.", "content": "The activity of phosphatidylinositol phosphodiesterase, purified from rat brain, against substrate in three forms, (a) multibilayer liposomes, (b) single bilayer vesicles of phosphatidylinositol and (c) phosphatidylinositol oriented as monolayers at the air-water interface, was examined. The reaction rate was similar against the two substrate dispersions prepared with the same phospholipid concentration, although there was a large difference in substrate surface area available to the enzyme, and this similarity could not be accounted for by any differences in the microviscosity of the hydrocarbon region of the phospholipid bilayers. The reaction showed apparent zero-order reaction kinetics until about 10% of the substrate had been degraded, whereupon the rate decreased. The reaction against monolayers of phosphatidylinositol was linear throughout the entire digestion of the film, provided that more than 0.25 mg of enzyme was present in the subphase. The pH optimum was 6.6. Bivalent ions )Ca2+, Mg2+, Co2+, Ni2+ and Mn2+) facilitated enzyme penetration into substrate monolayers, but the enzyme was only activated by Ca2+ (optimal concentration, 1mM) and to a lesser extent by Mg2+. The reaction rate was independent of initial surface pressures of less than about 22mN-m(-1) but at higher pressures the rate decreased. This decrease could be prevented by the addition of 10mol of octadecylamine/90mol of phosphatidylinositol to the substrate monolayer; the amine did not increase the rate of reaction in films of less than 22mN-m(-1).", "contents": "A comparison of the activity of phosphatidylinositol phosphodiesterase against substrate in dispersions and as monolayers at the air-water interface. The activity of phosphatidylinositol phosphodiesterase, purified from rat brain, against substrate in three forms, (a) multibilayer liposomes, (b) single bilayer vesicles of phosphatidylinositol and (c) phosphatidylinositol oriented as monolayers at the air-water interface, was examined. The reaction rate was similar against the two substrate dispersions prepared with the same phospholipid concentration, although there was a large difference in substrate surface area available to the enzyme, and this similarity could not be accounted for by any differences in the microviscosity of the hydrocarbon region of the phospholipid bilayers. The reaction showed apparent zero-order reaction kinetics until about 10% of the substrate had been degraded, whereupon the rate decreased. The reaction against monolayers of phosphatidylinositol was linear throughout the entire digestion of the film, provided that more than 0.25 mg of enzyme was present in the subphase. The pH optimum was 6.6. Bivalent ions )Ca2+, Mg2+, Co2+, Ni2+ and Mn2+) facilitated enzyme penetration into substrate monolayers, but the enzyme was only activated by Ca2+ (optimal concentration, 1mM) and to a lesser extent by Mg2+. The reaction rate was independent of initial surface pressures of less than about 22mN-m(-1) but at higher pressures the rate decreased. This decrease could be prevented by the addition of 10mol of octadecylamine/90mol of phosphatidylinositol to the substrate monolayer; the amine did not increase the rate of reaction in films of less than 22mN-m(-1)."}
{"id": "PMID:242323", "title": "The mechanism of C-4 demethylation during cholesterol biosynthesis.", "content": "The conversion of 4,4-dimethylcholest-7-enol into 4alpha-methylcholest-7-enol by rat liver microsomal preparations involves the decarboxylation of a sterol 3-oxo-4alpha-carboxylic acid. By using an (18)O-labelled substrate it was shown that this decarboxylation does not involve a Schiff-base intermediate.", "contents": "The mechanism of C-4 demethylation during cholesterol biosynthesis. The conversion of 4,4-dimethylcholest-7-enol into 4alpha-methylcholest-7-enol by rat liver microsomal preparations involves the decarboxylation of a sterol 3-oxo-4alpha-carboxylic acid. By using an (18)O-labelled substrate it was shown that this decarboxylation does not involve a Schiff-base intermediate."}
{"id": "PMID:242324", "title": "Rat haemoglobin heterogeneity. Two structurally distinct alpha chains and functional behaviour of selected components.", "content": "Six haemoglobins were separated analytically from haemolysates of adult Wistar rats (Rattus norvegicus) by cellulose acetate electrophoresis and preparatively by DEAE-cellulose chromatography. The globin chains were separated from unfractionated haemolysates by CM-cellulose chromatography by using a non-linear formic acid-pyridine gradient followed by CM-cellulose chromatography in 8M-urea by using a gradient of increasing Na+ concentration in phosphate buffer, pH 6.7. Two alpha chains and three non-alpha chains were identified. Chains isolated from purified haemoglobins were correlated with chains isolated from unfractionated haemolysates by electrophoresis on urea-starch gels to make presumptive assignments of the subunit composition of the six haemoglobin tetramers. Partial amino acid sequences were determined for the major and minor alpha chains. The oxygen equilibria of two of the major haemoglobin components and of the unfractionated haemolysate were examined at pH 7.5 and 8.0. The two purified haemoglobins exhibited similar oxygen affinities; the haemolysate, however, had a lower oxygen affinity than either of the two purified haemoglobins. Both the haemolysate and the two haemoglobins showed an alkaline Bohr effect larger than that of human haemoglobin A.", "contents": "Rat haemoglobin heterogeneity. Two structurally distinct alpha chains and functional behaviour of selected components. Six haemoglobins were separated analytically from haemolysates of adult Wistar rats (Rattus norvegicus) by cellulose acetate electrophoresis and preparatively by DEAE-cellulose chromatography. The globin chains were separated from unfractionated haemolysates by CM-cellulose chromatography by using a non-linear formic acid-pyridine gradient followed by CM-cellulose chromatography in 8M-urea by using a gradient of increasing Na+ concentration in phosphate buffer, pH 6.7. Two alpha chains and three non-alpha chains were identified. Chains isolated from purified haemoglobins were correlated with chains isolated from unfractionated haemolysates by electrophoresis on urea-starch gels to make presumptive assignments of the subunit composition of the six haemoglobin tetramers. Partial amino acid sequences were determined for the major and minor alpha chains. The oxygen equilibria of two of the major haemoglobin components and of the unfractionated haemolysate were examined at pH 7.5 and 8.0. The two purified haemoglobins exhibited similar oxygen affinities; the haemolysate, however, had a lower oxygen affinity than either of the two purified haemoglobins. Both the haemolysate and the two haemoglobins showed an alkaline Bohr effect larger than that of human haemoglobin A."}
{"id": "PMID:242325", "title": "Biosynthesis of heparin. Solubilization and partial characterization of N- and O-sulphotransferases.", "content": "Assay methods were developed enabling separate determination of N- and O-sulphotransferase activities in an enzyme preparation from mouse mastocytoma. N-Desulphoheparin and chemically N-acetylated heparan sulphate were used as specific exogenous sulphate acceptors in the transfer of [35S]sulphate residues from adenosine 3'-phosphate 5'-[35S]sulphatophosphate to amino and hydroxyl groups respectively. The resulting 35S-labelled polysaccharides were isolated as their cetylpyridinium complexes on filter paper. Sulphotransferases were solubilized from a mastocytoma microsomal fraction by treatment with detergent-alkali. The pH optimum for both enzymes was about 7.5 Km with regard to adenosine 3'-phosphate 5'-sulphatophosphate was estimated to be 2 X 10(-5) M for the N-sulphotransferase and 1 X 10(-4) M for the O-sulphotransferase(s). The enzymes required bivalent cations for maximum activity, Mn2+ stimulating both the N- and O-sulphotransferase four- to five-fold, whereas Ca2+ increased the N- but not the O-sulphotransferase activity. The O-sulphotransferase was found to be more sensitive to heat-inactivation, 60% of the activity being lost after 1 min at 50 degrees C, whereas only 15% of the N-sulphotransferase activity was lost. In contrast, the N-sulphotransferase was selectively inhibited (or inactivated) by NaCl; at 0.125 M-NaCl concentration the O-sulphotransferase activity was essentially unaffected, whereas the N-sulphotransferase activity was depressed by 80%. These results strongly indicate that N- and O-sulphate-transfer reactions should be ascribed to different enzymes, or, alternatively, to separate and independent active sites on the same enzyme molecule.", "contents": "Biosynthesis of heparin. Solubilization and partial characterization of N- and O-sulphotransferases. Assay methods were developed enabling separate determination of N- and O-sulphotransferase activities in an enzyme preparation from mouse mastocytoma. N-Desulphoheparin and chemically N-acetylated heparan sulphate were used as specific exogenous sulphate acceptors in the transfer of [35S]sulphate residues from adenosine 3'-phosphate 5'-[35S]sulphatophosphate to amino and hydroxyl groups respectively. The resulting 35S-labelled polysaccharides were isolated as their cetylpyridinium complexes on filter paper. Sulphotransferases were solubilized from a mastocytoma microsomal fraction by treatment with detergent-alkali. The pH optimum for both enzymes was about 7.5 Km with regard to adenosine 3'-phosphate 5'-sulphatophosphate was estimated to be 2 X 10(-5) M for the N-sulphotransferase and 1 X 10(-4) M for the O-sulphotransferase(s). The enzymes required bivalent cations for maximum activity, Mn2+ stimulating both the N- and O-sulphotransferase four- to five-fold, whereas Ca2+ increased the N- but not the O-sulphotransferase activity. The O-sulphotransferase was found to be more sensitive to heat-inactivation, 60% of the activity being lost after 1 min at 50 degrees C, whereas only 15% of the N-sulphotransferase activity was lost. In contrast, the N-sulphotransferase was selectively inhibited (or inactivated) by NaCl; at 0.125 M-NaCl concentration the O-sulphotransferase activity was essentially unaffected, whereas the N-sulphotransferase activity was depressed by 80%. These results strongly indicate that N- and O-sulphate-transfer reactions should be ascribed to different enzymes, or, alternatively, to separate and independent active sites on the same enzyme molecule."}
{"id": "PMID:242326", "title": "The binding of lanthanides to non-immune rabbit immunoglobulin G and its fragments.", "content": "The binding of Gd(III) to rabbit IgG (immunoglobulin G) and the Fab (N-terminal half of heavy and light chain), (Bab')2 (N-terminal half of heavy and light chains joined by inter-chain disulphide bond), Fc (C-terminal half of heavy-chain dimer)and pFc' (C-terminal quarter of heavy-chain dimer) fragments was demonstrated by measurements of the enhancement of the solvent-water proton relaxation rates in the appropriate Gd(III) solutions. At pH 5.5 there are six specific Gd(III)-binding sites on the IgG. These six sites can be divided into two classes; two very 'tight' sites on the Fc fragment (Kd approx. 5 muM) and two weaker sites on each Fab region (Kd approx. 140 muM). Ca(II) does not apparently compete for these metal-binding sites. The metal-binding parameters for IgG can be explained as the sum of the metal binding to the isolated Fab and Fc fragments, suggesting that there is no apparent interaction between the Fab and Fc regions in the IgG molecule. The binding of Gd(III) to Fab and Fc fragments was also monitored by measuring changes in the electron-spin-resonance spectrum of Gd(III) in the presence of each fragment and also by monitoring the effects of Gd(III) on the protein fluorescence at 340 nm (excitation 295 nm). The fluorescence of Tb(III) solutions of 545 nm (excitation 295 nm) is enhanced slightly on addition of Fab or Fc.", "contents": "The binding of lanthanides to non-immune rabbit immunoglobulin G and its fragments. The binding of Gd(III) to rabbit IgG (immunoglobulin G) and the Fab (N-terminal half of heavy and light chain), (Bab')2 (N-terminal half of heavy and light chains joined by inter-chain disulphide bond), Fc (C-terminal half of heavy-chain dimer)and pFc' (C-terminal quarter of heavy-chain dimer) fragments was demonstrated by measurements of the enhancement of the solvent-water proton relaxation rates in the appropriate Gd(III) solutions. At pH 5.5 there are six specific Gd(III)-binding sites on the IgG. These six sites can be divided into two classes; two very 'tight' sites on the Fc fragment (Kd approx. 5 muM) and two weaker sites on each Fab region (Kd approx. 140 muM). Ca(II) does not apparently compete for these metal-binding sites. The metal-binding parameters for IgG can be explained as the sum of the metal binding to the isolated Fab and Fc fragments, suggesting that there is no apparent interaction between the Fab and Fc regions in the IgG molecule. The binding of Gd(III) to Fab and Fc fragments was also monitored by measuring changes in the electron-spin-resonance spectrum of Gd(III) in the presence of each fragment and also by monitoring the effects of Gd(III) on the protein fluorescence at 340 nm (excitation 295 nm). The fluorescence of Tb(III) solutions of 545 nm (excitation 295 nm) is enhanced slightly on addition of Fab or Fc."}
{"id": "PMID:242509", "title": "Synergy of penicillin-netilmicin combinations against enterococci including strains highly resistant to streptomycin or kanamycin.", "content": "The in vitro activity of combinations of penicillin and netilimicin was determined against 20 clinical isolates of enterococci and compared with that obtained in simultaneous tests with penicillin/sisomicin, penicillin/streptomycin, and penicillin/kanamycin. Synergy between the two drugs in each combination was determined by the use of quantitative kill curves and was defined as a killing by the combination at least 100-fold greater than that produced by the most effective drug alone. Penicillin/netilmicin and penicillin/sisomicin combinations were found to be synergistic against the majority of isolates tested, including strains resistant to penicillin/streptomycin or penicillin/kanamycin combinations. This synergy with penicillin could be demonstrated at a concentration of </=7 mug/ml for either netilmicin or sisomicin. Studies on the kinetics of killing produced by these combinations showed the rate and extent of killing to be directly dependent upon the organism's relative susceptibility to the aminoglycoside alone and the aminoglycoside concentration in the combination. Results also indicated that the interaction between penicillin and netilmicin was true synergy; i.e., rapid and complete killing was produced by combinations containing each drug at concentrations insufficient to produce any killing alone, and the killing observed could not be produced by either drug alone at a concentration equivalent to the total drug concentration in the combination. The potential clinical application of this synergistic interaction should be investigated further, especially in view of recent reports showing netilmicin to be considerably less toxic than gentamicin in experimental animals.", "contents": "Synergy of penicillin-netilmicin combinations against enterococci including strains highly resistant to streptomycin or kanamycin. The in vitro activity of combinations of penicillin and netilimicin was determined against 20 clinical isolates of enterococci and compared with that obtained in simultaneous tests with penicillin/sisomicin, penicillin/streptomycin, and penicillin/kanamycin. Synergy between the two drugs in each combination was determined by the use of quantitative kill curves and was defined as a killing by the combination at least 100-fold greater than that produced by the most effective drug alone. Penicillin/netilmicin and penicillin/sisomicin combinations were found to be synergistic against the majority of isolates tested, including strains resistant to penicillin/streptomycin or penicillin/kanamycin combinations. This synergy with penicillin could be demonstrated at a concentration of </=7 mug/ml for either netilmicin or sisomicin. Studies on the kinetics of killing produced by these combinations showed the rate and extent of killing to be directly dependent upon the organism's relative susceptibility to the aminoglycoside alone and the aminoglycoside concentration in the combination. Results also indicated that the interaction between penicillin and netilmicin was true synergy; i.e., rapid and complete killing was produced by combinations containing each drug at concentrations insufficient to produce any killing alone, and the killing observed could not be produced by either drug alone at a concentration equivalent to the total drug concentration in the combination. The potential clinical application of this synergistic interaction should be investigated further, especially in view of recent reports showing netilmicin to be considerably less toxic than gentamicin in experimental animals."}
{"id": "PMID:242544", "title": "[The Tolosa-Hunt syndrome (author's transl)].", "content": "This paper reports 2 cases of the Tolosa-Hunt Syndrome and reviews 70 other cases reported in the literature. Common findings of this syndrome are the recurring painful ophthalmoplegia affecting the 3rd, 4th and 6th cranial nerve, as well as the first branch of the 5th and the optic nerve. No ethiologic factor has so far been found, but is regarded as a non specific inflammation in the area of the sinus cavernosus and adjacent orbital bone. Residual defects in about one third of affected persons is the normal course of the disease. Early diagnosis and initiation of steroid therapy results in quick relief of pain and may influence prognosis.", "contents": "[The Tolosa-Hunt syndrome (author's transl)]. This paper reports 2 cases of the Tolosa-Hunt Syndrome and reviews 70 other cases reported in the literature. Common findings of this syndrome are the recurring painful ophthalmoplegia affecting the 3rd, 4th and 6th cranial nerve, as well as the first branch of the 5th and the optic nerve. No ethiologic factor has so far been found, but is regarded as a non specific inflammation in the area of the sinus cavernosus and adjacent orbital bone. Residual defects in about one third of affected persons is the normal course of the disease. Early diagnosis and initiation of steroid therapy results in quick relief of pain and may influence prognosis."}
{"id": "PMID:242545", "title": "[Differential diagnosis of malignant and benign lymphomas of the CNS (author's transl)].", "content": "The following results were obtained from 37 cases of malignant lymphomas, including 8 eosinophilic granulomas: 1. Localisation: a. Plasmocytomas occur with approximately the same frequency in the spine and skull, but there is an exceptionally high incidence of multiple myelomas in the thoracic spine. Only in a few cases plasmocytomas of the skull lead to neurological symptoms; particularly when they are localised in the base of the skull. b. Lymphogranulomatosis affects only the thoracic vertebral column and leads less frequently to neurological complications compared with the multiple myelomas. c. Eosinophilic granulomas often attack the calvaria, but can also be found in the spine, the base of the cranium and the flat bones of the pelvis and the scapula. d. Leukaemias showed mainly intracerebral and intramedullary alterations: haemorrhages, leukaemic infiltrations and signs of degeneration. 2. a. Whenever the calvarium was affected than repeated complaints of headaches prevailed and only very few neurological signs or symptoms were complained. b. Tumors in the base of the cranium caused eye symptoms and various cranial nerve palsies but less frequently increased intracranial pressure. c. Tumors localised in the region of the spinal cord caused early signs like root-irritations (intercoastal neuralgia), diffuse dorsal pain and/or lumbalgia. Symptoms of spinal compression generally of an ascending character then developed within a few weeks. d. Neurological symptoms were the first to manifest themselves in all cases of plasmocytoma in half of our patients with Hodgkin's disease. 3. History and course: a. Generally in the cases of cranial involvement the previous history was less than half a year (visible changes or clear cut symptoms). Spinal tumors on the average had longer histories as did other extra-medullar spinal new growth. Similar courses were seen in multiple myelomas and granulomas. b. Solitary plasmocytomas were very rare but seem to have a considerably better prognosis than in case of multiple occurrence.", "contents": "[Differential diagnosis of malignant and benign lymphomas of the CNS (author's transl)]. The following results were obtained from 37 cases of malignant lymphomas, including 8 eosinophilic granulomas: 1. Localisation: a. Plasmocytomas occur with approximately the same frequency in the spine and skull, but there is an exceptionally high incidence of multiple myelomas in the thoracic spine. Only in a few cases plasmocytomas of the skull lead to neurological symptoms; particularly when they are localised in the base of the skull. b. Lymphogranulomatosis affects only the thoracic vertebral column and leads less frequently to neurological complications compared with the multiple myelomas. c. Eosinophilic granulomas often attack the calvaria, but can also be found in the spine, the base of the cranium and the flat bones of the pelvis and the scapula. d. Leukaemias showed mainly intracerebral and intramedullary alterations: haemorrhages, leukaemic infiltrations and signs of degeneration. 2. a. Whenever the calvarium was affected than repeated complaints of headaches prevailed and only very few neurological signs or symptoms were complained. b. Tumors in the base of the cranium caused eye symptoms and various cranial nerve palsies but less frequently increased intracranial pressure. c. Tumors localised in the region of the spinal cord caused early signs like root-irritations (intercoastal neuralgia), diffuse dorsal pain and/or lumbalgia. Symptoms of spinal compression generally of an ascending character then developed within a few weeks. d. Neurological symptoms were the first to manifest themselves in all cases of plasmocytoma in half of our patients with Hodgkin's disease. 3. History and course: a. Generally in the cases of cranial involvement the previous history was less than half a year (visible changes or clear cut symptoms). Spinal tumors on the average had longer histories as did other extra-medullar spinal new growth. Similar courses were seen in multiple myelomas and granulomas. b. Solitary plasmocytomas were very rare but seem to have a considerably better prognosis than in case of multiple occurrence."}
{"id": "PMID:242607", "title": "[The combination effect of ampicillin and dicloxacillin on the strains of Bacteriodes fragilis isolated from clinical specimens (author's transl)].", "content": "The antimicrobial activities of ampicillin (ABPC) and dicloxacillin (MDIPC) alone were tested in 100 strains of B. fragilis isolated from clinical specimens, and combined activity of ABPC and MDIPC was investigated employing a chequer board titration method (Box method) with agar plates and liquid media. The following results were obtained. 1. Of the 100 strains tested, approximately 33% were shown to have MICs of ABPC greater than 100 mcg/ml, whereas 92% of strains were greater than 100 mcg/ml to MDIPC. 2. In the combination, antimicrobial activities were demonstrated additive or synergistic action in almost strains tested. 3. A combined effect of these drugs was proved by agar dilution method for the strains, for which the same effect was shown by the tube dilution method. 4. For ABPC-resistant strains, no increase in antibacterial activity of these drugs by combination was demonstrated.", "contents": "[The combination effect of ampicillin and dicloxacillin on the strains of Bacteriodes fragilis isolated from clinical specimens (author's transl)]. The antimicrobial activities of ampicillin (ABPC) and dicloxacillin (MDIPC) alone were tested in 100 strains of B. fragilis isolated from clinical specimens, and combined activity of ABPC and MDIPC was investigated employing a chequer board titration method (Box method) with agar plates and liquid media. The following results were obtained. 1. Of the 100 strains tested, approximately 33% were shown to have MICs of ABPC greater than 100 mcg/ml, whereas 92% of strains were greater than 100 mcg/ml to MDIPC. 2. In the combination, antimicrobial activities were demonstrated additive or synergistic action in almost strains tested. 3. A combined effect of these drugs was proved by agar dilution method for the strains, for which the same effect was shown by the tube dilution method. 4. For ABPC-resistant strains, no increase in antibacterial activity of these drugs by combination was demonstrated."}
{"id": "PMID:242733", "title": "The penicillins.", "content": "The penicillins as a group are the most frequently and widely used of the antimicrobial agents because they are effective, low in toxicity, and relatively inexpensive. Effectiveness is due to the bactericidal action, the excellent distribution throughout the body spaces, and the wide spectrum of activity. Knowledge of the variation in spectrum of activity of the various types of penicillins is needed for effective use of the proper drug against individual infections. Allergenicity is the most frequent and serious problem associated with the use of penicillins. However, individual penicillin drugs do have other toxic side effects. The older penicillins are so inexpensive that the cost of their use need hardly be considered, whereas the newer penicillins are expensive and should be used only when they are clearly more effective for treatment than are drugs such as penicillin G.", "contents": "The penicillins. The penicillins as a group are the most frequently and widely used of the antimicrobial agents because they are effective, low in toxicity, and relatively inexpensive. Effectiveness is due to the bactericidal action, the excellent distribution throughout the body spaces, and the wide spectrum of activity. Knowledge of the variation in spectrum of activity of the various types of penicillins is needed for effective use of the proper drug against individual infections. Allergenicity is the most frequent and serious problem associated with the use of penicillins. However, individual penicillin drugs do have other toxic side effects. The older penicillins are so inexpensive that the cost of their use need hardly be considered, whereas the newer penicillins are expensive and should be used only when they are clearly more effective for treatment than are drugs such as penicillin G."}
{"id": "PMID:242796", "title": "The characterization of phosphoseryl tRNA from lactating bovine mammary gland.", "content": "BD-cellulose and RPC-5 chromatography of tRNA isolated from lactating bovine mammary gland showed the presence of four seryl-tRNA isoacceptors. The species, tRNA IV Ser, with the strongest affinity for BD-cellulose (required ethanol in the elution buffer) could be phosphorylated in the presence of serine, [gamma-32 P]-ATP, seryl-tRNA synthetase and phosphotransferase activity from the same tissue. O-Phosphoserine was identified as the 32P-labelled product after mild alkaline hydrolysis of this aminoacylated tRNA. Pancreatic ribonuclease treatment of the aminoacylated tRNA yielded a labelled product which was identified as phosphoseryladenosine. These results indicated there is a specific phosphoseryl tRNA species in lactating bovine mammary gland. It appears that the formation of phosphoseryl-tRNA proceeds by enzymic phosphorylation of seryl-tRNA.", "contents": "The characterization of phosphoseryl tRNA from lactating bovine mammary gland. BD-cellulose and RPC-5 chromatography of tRNA isolated from lactating bovine mammary gland showed the presence of four seryl-tRNA isoacceptors. The species, tRNA IV Ser, with the strongest affinity for BD-cellulose (required ethanol in the elution buffer) could be phosphorylated in the presence of serine, [gamma-32 P]-ATP, seryl-tRNA synthetase and phosphotransferase activity from the same tissue. O-Phosphoserine was identified as the 32P-labelled product after mild alkaline hydrolysis of this aminoacylated tRNA. Pancreatic ribonuclease treatment of the aminoacylated tRNA yielded a labelled product which was identified as phosphoseryladenosine. These results indicated there is a specific phosphoseryl tRNA species in lactating bovine mammary gland. It appears that the formation of phosphoseryl-tRNA proceeds by enzymic phosphorylation of seryl-tRNA."}
{"id": "PMID:242797", "title": "Properties of phenylalanine transfer ribonucleic acid with modified 3'-terminal end in protein biosynthesis using a rabbit reticulocyte cell-free system: effect of the replacement of cytidine residues from the CpCpA end of tRNA by 5-iodocytidine or 2-thiocytidine.", "content": "Phe-tRNA Phe from yeast containing 2-thiocytidine or 5-iodocytidine in position 75 of the polynucleotide chain or Phe-tRNA Phe in which both positions 74 and 75 were substituted by 5-iodocytidine were investigated in the poly U-dependent polyphenylalanine synthesis on ribosomes from rabbit reticulocytes. Phe-tRNA Phe-Cps2CpA was nearly as active as the native Phe-tRNA Phe-CpCpA in the overall process. Phe-tRNA Phe-Cpi 5CpA as well as Phe-tRNA Phe-i5Cpi 5CpA were considerably less active than the native species. Investigation of individual steps of protein biosynthesis with these modified substrates revealed that the donor activity of peptidyl-tRNAs which contain 5-iodocytidine in their 3'-terminus is strongly imparied suggesting exacting structural requirements for the interaction of the CpCpA end of tRNA with the ribosomal P-site.", "contents": "Properties of phenylalanine transfer ribonucleic acid with modified 3'-terminal end in protein biosynthesis using a rabbit reticulocyte cell-free system: effect of the replacement of cytidine residues from the CpCpA end of tRNA by 5-iodocytidine or 2-thiocytidine. Phe-tRNA Phe from yeast containing 2-thiocytidine or 5-iodocytidine in position 75 of the polynucleotide chain or Phe-tRNA Phe in which both positions 74 and 75 were substituted by 5-iodocytidine were investigated in the poly U-dependent polyphenylalanine synthesis on ribosomes from rabbit reticulocytes. Phe-tRNA Phe-Cps2CpA was nearly as active as the native Phe-tRNA Phe-CpCpA in the overall process. Phe-tRNA Phe-Cpi 5CpA as well as Phe-tRNA Phe-i5Cpi 5CpA were considerably less active than the native species. Investigation of individual steps of protein biosynthesis with these modified substrates revealed that the donor activity of peptidyl-tRNAs which contain 5-iodocytidine in their 3'-terminus is strongly imparied suggesting exacting structural requirements for the interaction of the CpCpA end of tRNA with the ribosomal P-site."}
{"id": "PMID:242909", "title": "Unusual Pseudomonas corneal ulcers.", "content": "Two rare species of Pseudomonas were isolated from corneal ulcers in two patients. In the first case P. acidovorans was isolated and suspected as the primary pathogenic microorganism in human disease. In the second case P. stutzeri was isolated from ocular sources, but this is the first report of its role in causing corneal disease. The patient in the second case had a scarred cornea, possibly caused by a previous herpetic infection, and this may have been a predisposing factor to the development of the infection by P. stutzeri. Susceptibility studies of both organisms revealed sensitivity to a wide range of antibiotics but resistance to carbenicillin, a drug currently used in the treatment of infections from P. aeruginosa.", "contents": "Unusual Pseudomonas corneal ulcers. Two rare species of Pseudomonas were isolated from corneal ulcers in two patients. In the first case P. acidovorans was isolated and suspected as the primary pathogenic microorganism in human disease. In the second case P. stutzeri was isolated from ocular sources, but this is the first report of its role in causing corneal disease. The patient in the second case had a scarred cornea, possibly caused by a previous herpetic infection, and this may have been a predisposing factor to the development of the infection by P. stutzeri. Susceptibility studies of both organisms revealed sensitivity to a wide range of antibiotics but resistance to carbenicillin, a drug currently used in the treatment of infections from P. aeruginosa."}
{"id": "PMID:242911", "title": "Resistance to six aminoglycosidic aminocyclitol antibiotics among enterococci: prevalence, evolution, and relationship to synergism with penicillin.", "content": "Two hundred and three recent clinical isolates of enterococci were tested for susceptibility to streptomycin, kanamycin, amikacin, gentamicin, sisomicin, and tobramycin. Depending upon the source of the isolate, 36 to 54% of the enterococci demonstrated high-level resistance (minimal inhibitory concentration, >2,000 mug/ml) to streptomycin, 16 to 49% to kanamycin, and 0 to 14% to amikacin. None of the strains was highly resistant to gentamicin, sisomicin, or tobramycin. A comparison with isolates of enterococci obtained in 1968 revealed that there has been a decrease in prevalence of high-level resistance among organisms isolated from wound cultures in 1976. However, no decrease in resistance to streptomycin or kanamycin was demonstrated among blood or urine isolates. Penicillin, combined with gentamicin, sisomicin, or tobramycin, was synergistic against all 10 strains of Streptococcus faecalis subjected to formal testing. For streptomycin and kanamycin, the presence or absence of synergism with penicillin correlated with the absence or presence of high-level aminoglycoside resistance. High-level resistance to amikacin was seen in only 1 of the 10 strains. Nonetheless, combinations of penicillin plus amikacin failed to produce synergistic killing against 6 of the 10 strains. Indeed, the combination was synergistic only against those four strains that were susceptible to high levels of kanamycin.", "contents": "Resistance to six aminoglycosidic aminocyclitol antibiotics among enterococci: prevalence, evolution, and relationship to synergism with penicillin. Two hundred and three recent clinical isolates of enterococci were tested for susceptibility to streptomycin, kanamycin, amikacin, gentamicin, sisomicin, and tobramycin. Depending upon the source of the isolate, 36 to 54% of the enterococci demonstrated high-level resistance (minimal inhibitory concentration, >2,000 mug/ml) to streptomycin, 16 to 49% to kanamycin, and 0 to 14% to amikacin. None of the strains was highly resistant to gentamicin, sisomicin, or tobramycin. A comparison with isolates of enterococci obtained in 1968 revealed that there has been a decrease in prevalence of high-level resistance among organisms isolated from wound cultures in 1976. However, no decrease in resistance to streptomycin or kanamycin was demonstrated among blood or urine isolates. Penicillin, combined with gentamicin, sisomicin, or tobramycin, was synergistic against all 10 strains of Streptococcus faecalis subjected to formal testing. For streptomycin and kanamycin, the presence or absence of synergism with penicillin correlated with the absence or presence of high-level aminoglycoside resistance. High-level resistance to amikacin was seen in only 1 of the 10 strains. Nonetheless, combinations of penicillin plus amikacin failed to produce synergistic killing against 6 of the 10 strains. Indeed, the combination was synergistic only against those four strains that were susceptible to high levels of kanamycin."}
{"id": "PMID:242930", "title": "Kinetic analysis of fraction I protein biosynthesis in young protoplasts of tobacco leaves.", "content": "At maximum inhibition chloramphenicol reduced [35S] methionine incorporation into acid-insoluble materials of sterile protoplasts from young tobacco leaves 5-7 cm in length by 30% compared to 70% by cycloheximide, indicating that 30% of the [35S] methionine became incorporated into chloroplast proteins and 70% into cytoplasmic proteins. [35S] Methionine became incorporated into both the large and small subunits of Fraction I protein, the major soluble protein of chloroplasts. Rifampicin and streptolydigin inhibited [3H] uridine incorporation into the 23 and 16 S rRNAs of chloroplasts to a much greater extent than into the 25 and 18 S cytoplasmic rRNAs. Rifampicin inhibited [35S] metionine incorporation into Fraction I protein after the third hour of incubation; streptolydigin after 2 h, the former evidently preventing initiation of mRNA for the large subunit of Fraction I protein and the latter its elongation. About 2.5 h was required between initiation of the large subunit mRNA synthesis, and appearance of the protein. It was estimated that 45 min is required for transcription of the mRNA which has a half-life of 2 h and that 105 min is required for its translation into approximately 350 amino acids constituting the large subunit monomeric polypeptide. The effect of chloramphenicol, cycloheximide and 2-(4-methyl-2,6-dinitroanaline)-N-methyl propionamide, the latter an inhibitor of protein initiation by 80 S ribosomes, on kinetics of Fraction I protein synthesis indicate that protoplasts contain a pool of small subunit polypeptides and that 30 min is required to polymerize the approximately 100 amino acids constituting the primary structure.", "contents": "Kinetic analysis of fraction I protein biosynthesis in young protoplasts of tobacco leaves. At maximum inhibition chloramphenicol reduced [35S] methionine incorporation into acid-insoluble materials of sterile protoplasts from young tobacco leaves 5-7 cm in length by 30% compared to 70% by cycloheximide, indicating that 30% of the [35S] methionine became incorporated into chloroplast proteins and 70% into cytoplasmic proteins. [35S] Methionine became incorporated into both the large and small subunits of Fraction I protein, the major soluble protein of chloroplasts. Rifampicin and streptolydigin inhibited [3H] uridine incorporation into the 23 and 16 S rRNAs of chloroplasts to a much greater extent than into the 25 and 18 S cytoplasmic rRNAs. Rifampicin inhibited [35S] metionine incorporation into Fraction I protein after the third hour of incubation; streptolydigin after 2 h, the former evidently preventing initiation of mRNA for the large subunit of Fraction I protein and the latter its elongation. About 2.5 h was required between initiation of the large subunit mRNA synthesis, and appearance of the protein. It was estimated that 45 min is required for transcription of the mRNA which has a half-life of 2 h and that 105 min is required for its translation into approximately 350 amino acids constituting the large subunit monomeric polypeptide. The effect of chloramphenicol, cycloheximide and 2-(4-methyl-2,6-dinitroanaline)-N-methyl propionamide, the latter an inhibitor of protein initiation by 80 S ribosomes, on kinetics of Fraction I protein synthesis indicate that protoplasts contain a pool of small subunit polypeptides and that 30 min is required to polymerize the approximately 100 amino acids constituting the primary structure."}
{"id": "PMID:242927", "title": "[Diarrhea outbreak and bacterial resistance to ampicillin in newborns].", "content": "Twenty-eight healthy neonates from the San Juan de Dios Hospital were studied to determine the pattern of antibiotic resistance of indigenous intestinal bacteria. Sixty-eight per cent of infants had enterobacteriaceae resistant to several wide-spectrum antibiotics, including ampicillin; 28 per cent of the cultures had plasmid-mediated ampicillin resistance. In the course of the study, an outbreak of 10 acute cases of diarrhea occurred, not associated to any of the commonly known agents, including the rotaviruses. Enterobacteriaceae multiple resistant were isolated from all cases; ampicillin-resistant strains were found in all; those resistances were mediated by transmissible plasmids. Several sites of the Neonatology Ward were sampled and two yielded E. coli with resistance to 8 drugs transmissible in vitro. The outbreak was controlled after strict hygienic measures were established in the ward. A following sample showed a decrease in indigenous antibiotic-resistant strains, especially E. coli; however, plasmid mediated resistant Klebsiella was still isolated several months later. The need to regulate the use of antibiotics; to educate the medical personnel and the public in general and to modify the hospital norms and regulations are discussed in the paper.", "contents": "[Diarrhea outbreak and bacterial resistance to ampicillin in newborns]. Twenty-eight healthy neonates from the San Juan de Dios Hospital were studied to determine the pattern of antibiotic resistance of indigenous intestinal bacteria. Sixty-eight per cent of infants had enterobacteriaceae resistant to several wide-spectrum antibiotics, including ampicillin; 28 per cent of the cultures had plasmid-mediated ampicillin resistance. In the course of the study, an outbreak of 10 acute cases of diarrhea occurred, not associated to any of the commonly known agents, including the rotaviruses. Enterobacteriaceae multiple resistant were isolated from all cases; ampicillin-resistant strains were found in all; those resistances were mediated by transmissible plasmids. Several sites of the Neonatology Ward were sampled and two yielded E. coli with resistance to 8 drugs transmissible in vitro. The outbreak was controlled after strict hygienic measures were established in the ward. A following sample showed a decrease in indigenous antibiotic-resistant strains, especially E. coli; however, plasmid mediated resistant Klebsiella was still isolated several months later. The need to regulate the use of antibiotics; to educate the medical personnel and the public in general and to modify the hospital norms and regulations are discussed in the paper."}
{"id": "PMID:242934", "title": "Patterns of drug use among methadone maintenance patients in Los Angeles county.", "content": "Any evaluation of the effectiveness of methadone maintenance programmes in rehabilitating heroin addicts is inherently complex and subject to varied interpretations, both scientific and philosophical. From a scientific perspective, it is necessary to accumulate sufficient factual data to validate any hypothetical conclusions. A retrospective survey of drug-use patterns among the methadone maintenance population of Los Angeles County was undertaken in an effort to provide some such information. Over 5,000 urine samples from 730 paitients were analysed for eleven drugs over a two-month period in 1975. Over 23 per cent of these samples were found positive for a drug other than methadone and 80 per cent of these positives were attributed to illicitly used drugs. The opiates (codeine and morphine) comprised almost 74 per cent of the drugs found while barbiturates and amphetamine and/or methamphetamine contributed 16 per cent and 10 per cent to the total, respectively.", "contents": "Patterns of drug use among methadone maintenance patients in Los Angeles county. Any evaluation of the effectiveness of methadone maintenance programmes in rehabilitating heroin addicts is inherently complex and subject to varied interpretations, both scientific and philosophical. From a scientific perspective, it is necessary to accumulate sufficient factual data to validate any hypothetical conclusions. A retrospective survey of drug-use patterns among the methadone maintenance population of Los Angeles County was undertaken in an effort to provide some such information. Over 5,000 urine samples from 730 paitients were analysed for eleven drugs over a two-month period in 1975. Over 23 per cent of these samples were found positive for a drug other than methadone and 80 per cent of these positives were attributed to illicitly used drugs. The opiates (codeine and morphine) comprised almost 74 per cent of the drugs found while barbiturates and amphetamine and/or methamphetamine contributed 16 per cent and 10 per cent to the total, respectively."}
{"id": "PMID:242941", "title": "Further evidence that elongation factor 1 remains bound to ribosomes during peptide chain elongation.", "content": "This paper describes three types of experiments which indicate that the binding sites for elongation factor 1 (EF-1) and elongation factor 2 (EF-2) on ascites cell ribosomes are not identical and perhaps not even overlapping. The experimental evidence presented includes direct competitive binding of labeled elongation factors to ribosomes as well as the influence of pokeweed antiviral protein and Escherichia coli anti L7/L12 proteins on the binding and function of the two factors. It is further shown that EF-1beta from Artemia salina does not function in displacing EF-1 from mouse ascites tumor cell ribosomes. These results also support our recently proposed model that EF-1 remains bound to the ribosome during the peptide chain elongation cycle.", "contents": "Further evidence that elongation factor 1 remains bound to ribosomes during peptide chain elongation. This paper describes three types of experiments which indicate that the binding sites for elongation factor 1 (EF-1) and elongation factor 2 (EF-2) on ascites cell ribosomes are not identical and perhaps not even overlapping. The experimental evidence presented includes direct competitive binding of labeled elongation factors to ribosomes as well as the influence of pokeweed antiviral protein and Escherichia coli anti L7/L12 proteins on the binding and function of the two factors. It is further shown that EF-1beta from Artemia salina does not function in displacing EF-1 from mouse ascites tumor cell ribosomes. These results also support our recently proposed model that EF-1 remains bound to the ribosome during the peptide chain elongation cycle."}
{"id": "PMID:242957", "title": "[Prevention and therapy of respiratory distress syndrome in premature infants by means of bromhexine metabolite VIII. Animal experimental studies on the therapeutic efficacy of bromhexine metabolite VIII in premature respiratory distress syndrome].", "content": "In preparing a clinical study 14C-labelled bromhexine metabolite VIII was applied intraamnially in animal experiments. The distribution was measured in different maternal and fetal organs by thinlayer chromatography and autoradiography. A complete placental passage was found in both directions. An organspecific accumulation in the fetal lungs could not be demonstrated.", "contents": "[Prevention and therapy of respiratory distress syndrome in premature infants by means of bromhexine metabolite VIII. Animal experimental studies on the therapeutic efficacy of bromhexine metabolite VIII in premature respiratory distress syndrome]. In preparing a clinical study 14C-labelled bromhexine metabolite VIII was applied intraamnially in animal experiments. The distribution was measured in different maternal and fetal organs by thinlayer chromatography and autoradiography. A complete placental passage was found in both directions. An organspecific accumulation in the fetal lungs could not be demonstrated."}
{"id": "PMID:242958", "title": "[Prognosis and therapy of sporadic seizures (author's transl)].", "content": "Eighty-five patients were admitted to the hospital under the preliminary diagnosis of epileptic seizures. None of them had more than five seizures before admission. Sixty-five of these 85 patients had a neurological and electroencephalographic follow-up examination 5 to 7 years later. Another 8 had been readmitted before. From these 8 the diagnosis of cerebral tumor was made in 3 patients. In almost half of the remaining 70 cases the etiology of seizures remained uncertain. The leading known etiologic factors were chronic alcoholism, head injury and perinatal brain damage. Before admission seizures recurred once or twice a year in most patients. After discharge from the hospital 25 patients were without further seizures, 15 of the seizure-free group never received anti-epileptic treatment. The remaining 10 were without medication for a period of time before the follow-up. All seizure-free patients were given the diagnosis of very rare grand mal seizures or seizures of uncertain origin. Only two of the untreated group (total of 17) had seizures after discharge. These findings show that recurrence of seizures was predictable, when patients were discharged. Predictors of recurrance were \"treatment\" or \"no treatment\" given initially. Antiepileptic medication should be given in cases of one seizure or more a year, when epileptic origin is certain. Very rare seizures and seizures of uncertain origin may stay without antiepileptic treatment. Sporadic seizures are benign in most cases - comparable to seizures of late onset. Both groups overlap.", "contents": "[Prognosis and therapy of sporadic seizures (author's transl)]. Eighty-five patients were admitted to the hospital under the preliminary diagnosis of epileptic seizures. None of them had more than five seizures before admission. Sixty-five of these 85 patients had a neurological and electroencephalographic follow-up examination 5 to 7 years later. Another 8 had been readmitted before. From these 8 the diagnosis of cerebral tumor was made in 3 patients. In almost half of the remaining 70 cases the etiology of seizures remained uncertain. The leading known etiologic factors were chronic alcoholism, head injury and perinatal brain damage. Before admission seizures recurred once or twice a year in most patients. After discharge from the hospital 25 patients were without further seizures, 15 of the seizure-free group never received anti-epileptic treatment. The remaining 10 were without medication for a period of time before the follow-up. All seizure-free patients were given the diagnosis of very rare grand mal seizures or seizures of uncertain origin. Only two of the untreated group (total of 17) had seizures after discharge. These findings show that recurrence of seizures was predictable, when patients were discharged. Predictors of recurrance were \"treatment\" or \"no treatment\" given initially. Antiepileptic medication should be given in cases of one seizure or more a year, when epileptic origin is certain. Very rare seizures and seizures of uncertain origin may stay without antiepileptic treatment. Sporadic seizures are benign in most cases - comparable to seizures of late onset. Both groups overlap."}
{"id": "PMID:242959", "title": "[Cardiovascular side effects of tricyclic psychopharmaca under special consideration of the ECG (author's transl)].", "content": "The cardialvascular side effects of tricyclic psychopharmaca.- alteration of blood pressure and heart rate in connection with hemodynamic effects, the \"antiarrhythmic activity\" and the abnormal ECG-findings - are reviewed. The ECG-changes are discussed in detail. They can be divided in disturbances of rhythm, conduction and repolarisation. After a survey over the usual interpretation of the ECG-findings a hypothesis for better understanding is presented. There is supposed - in close relation to the dosage - a direct affection of the myocardium (by enzyme suppression, disturbance of the membrane permeability?) connected with reflectory vegetative mechanisms which can be modified by factors like kind and severity of the illness, diurnal changes and many external influences, difficult to quantify and objectivate. So the transitory and alternating ECG-findings could be interpretated as a state-depending summation, subtraction or potentiation of the cited single effects.", "contents": "[Cardiovascular side effects of tricyclic psychopharmaca under special consideration of the ECG (author's transl)]. The cardialvascular side effects of tricyclic psychopharmaca.- alteration of blood pressure and heart rate in connection with hemodynamic effects, the \"antiarrhythmic activity\" and the abnormal ECG-findings - are reviewed. The ECG-changes are discussed in detail. They can be divided in disturbances of rhythm, conduction and repolarisation. After a survey over the usual interpretation of the ECG-findings a hypothesis for better understanding is presented. There is supposed - in close relation to the dosage - a direct affection of the myocardium (by enzyme suppression, disturbance of the membrane permeability?) connected with reflectory vegetative mechanisms which can be modified by factors like kind and severity of the illness, diurnal changes and many external influences, difficult to quantify and objectivate. So the transitory and alternating ECG-findings could be interpretated as a state-depending summation, subtraction or potentiation of the cited single effects."}
{"id": "PMID:242960", "title": "[A progressive systemic sclerosis like disease due to anticonvulsive therapy? (author's transl)].", "content": "Two cases are presented which have been treated anticonvulsively for many years - especially with Phenytoin and Mephenytoin. The clinical syndrom as well as the changes of the connective tissue show transitions of Progressive systemic sklerosis (PSS) to systemic Lupus Erythematodes (SLE) and Dermatomyositis. The correlation with the therapy is reflected in consideration of immunological phenomenons.", "contents": "[A progressive systemic sclerosis like disease due to anticonvulsive therapy? (author's transl)]. Two cases are presented which have been treated anticonvulsively for many years - especially with Phenytoin and Mephenytoin. The clinical syndrom as well as the changes of the connective tissue show transitions of Progressive systemic sklerosis (PSS) to systemic Lupus Erythematodes (SLE) and Dermatomyositis. The correlation with the therapy is reflected in consideration of immunological phenomenons."}
{"id": "PMID:242961", "title": "[Age-dependent changes of the central part of the lateral ventricle of the brain in children (author's transl)].", "content": "In 504 children of different age groups the width of the body region of the lateral ventricles was measured by means of one-dimensional echoencephalography in a cross-sectional study. During the first two months of life, there is in the average a decrease of the width of the body region and afterwards an increase until the age of four. It can be assumed that the phenomenon of the decrease is caused by the rapid growth of brain in this period of life. The one-dimensional echoencephalography can be used as screening test for the diagnosis of neuropaediatric disorders.", "contents": "[Age-dependent changes of the central part of the lateral ventricle of the brain in children (author's transl)]. In 504 children of different age groups the width of the body region of the lateral ventricles was measured by means of one-dimensional echoencephalography in a cross-sectional study. During the first two months of life, there is in the average a decrease of the width of the body region and afterwards an increase until the age of four. It can be assumed that the phenomenon of the decrease is caused by the rapid growth of brain in this period of life. The one-dimensional echoencephalography can be used as screening test for the diagnosis of neuropaediatric disorders."}
{"id": "PMID:242988", "title": "Preferential usage of tRNA isoaccepting species in collagen synthesis.", "content": "A new double label technique is described for determining the usage of individual isoaccepting tRNA species by in vitro protein-synthesizing systems. Employing this method we show that of four major species of glycyl-tRNA one which is cognate to GGU and GGC is used predominantly in collagen synthesis by polysomes isolated from embryonic chick calvaria. A similar preferential usage was found for one of two alanyl-tRNA species. No preference for any particular isoaccepting tRNA species was observed in the synthesis of noncollagenous proteins by either calvaria or liver polysomes except for the disproportionate usage of one lysyl-tRNA species. Whether such preferential usage permits translational control of collagen synthesis in vivo remains to be determined.", "contents": "Preferential usage of tRNA isoaccepting species in collagen synthesis. A new double label technique is described for determining the usage of individual isoaccepting tRNA species by in vitro protein-synthesizing systems. Employing this method we show that of four major species of glycyl-tRNA one which is cognate to GGU and GGC is used predominantly in collagen synthesis by polysomes isolated from embryonic chick calvaria. A similar preferential usage was found for one of two alanyl-tRNA species. No preference for any particular isoaccepting tRNA species was observed in the synthesis of noncollagenous proteins by either calvaria or liver polysomes except for the disproportionate usage of one lysyl-tRNA species. Whether such preferential usage permits translational control of collagen synthesis in vivo remains to be determined."}
{"id": "PMID:243028", "title": "[Basic and clinical studies on AMPC (amoxicillin) in the field of surgery (author's transl)].", "content": "In the present study, amoxicillin was compared with other antibiotics with respect to sensitivity, levels achieved in the blood and various organs and clinical results. We would like to make further studies accumulated number of cases.", "contents": "[Basic and clinical studies on AMPC (amoxicillin) in the field of surgery (author's transl)]. In the present study, amoxicillin was compared with other antibiotics with respect to sensitivity, levels achieved in the blood and various organs and clinical results. We would like to make further studies accumulated number of cases."}
{"id": "PMID:243078", "title": "Evaluation of a pilot school health education program for asthmatic children.", "content": "A pilot program was conducted and evaluated as a part of the development of a health education program designed to meet the needs of a specified target population. By focusing on a group of children with a common chronic health problem, it was possible to measure specific variables to evaluate the effectiveness of the program. Outcome evaluation together with subjective process information resulted in modification and changes in the program prior to implementation with a larger number of children and schools. The pilot phase conducted with a small number of children was demonstrated to be a critical part of the overall program development.", "contents": "Evaluation of a pilot school health education program for asthmatic children. A pilot program was conducted and evaluated as a part of the development of a health education program designed to meet the needs of a specified target population. By focusing on a group of children with a common chronic health problem, it was possible to measure specific variables to evaluate the effectiveness of the program. Outcome evaluation together with subjective process information resulted in modification and changes in the program prior to implementation with a larger number of children and schools. The pilot phase conducted with a small number of children was demonstrated to be a critical part of the overall program development."}
{"id": "PMID:243082", "title": "The effect of nutrition education on dietary habits on fifth-graders.", "content": "Two fifth-grade classes of 45 students, a majority in the Mexican-American culture, participated in the five month study. One group was taught a series of eight nutrition education units emphasizing weight control while the other group received no nutrition instruction. Pretests and posttests were given to each group and a 24-hour dietary recall was obtained. Findings from the written pretest and posttest showed that the group receiving nutrition instruction learned a significantly (p less than .01) greater number of nutrition concepts than the control group. Dietary intakes revealed that the diets of the experimental group did not improve after nutrition instruction. A majority of postdietary intakes met less than 50% of the RDA.", "contents": "The effect of nutrition education on dietary habits on fifth-graders. Two fifth-grade classes of 45 students, a majority in the Mexican-American culture, participated in the five month study. One group was taught a series of eight nutrition education units emphasizing weight control while the other group received no nutrition instruction. Pretests and posttests were given to each group and a 24-hour dietary recall was obtained. Findings from the written pretest and posttest showed that the group receiving nutrition instruction learned a significantly (p less than .01) greater number of nutrition concepts than the control group. Dietary intakes revealed that the diets of the experimental group did not improve after nutrition instruction. A majority of postdietary intakes met less than 50% of the RDA."}
{"id": "PMID:243085", "title": "Results of school screening for scoliosis in the San Juan Unified School District, Sacramento, California.", "content": "Annual routine school examination for scoliosis has been established in the San Juan Unified School District. Additionally, several parochial schools and other schools in the county or nearby towns have expressed interest in such a program. A rapid, effective method, taking no more than 30 seconds per child, has been used to detect spinal curvature. The program is beneficial for those identified with scoliosis, because early detection, followed by proper treatment, can prevent major surgery. The need for careful school nurse follow-up must be emphasized. A standing x-ray and evaluation by a qualified physician are imperative. If scoliosis is diagnosed, the school nurse can be a very effective contact in assisting the students by discussing exercise or brace care and by providing encouragement and general supportive help.", "contents": "Results of school screening for scoliosis in the San Juan Unified School District, Sacramento, California. Annual routine school examination for scoliosis has been established in the San Juan Unified School District. Additionally, several parochial schools and other schools in the county or nearby towns have expressed interest in such a program. A rapid, effective method, taking no more than 30 seconds per child, has been used to detect spinal curvature. The program is beneficial for those identified with scoliosis, because early detection, followed by proper treatment, can prevent major surgery. The need for careful school nurse follow-up must be emphasized. A standing x-ray and evaluation by a qualified physician are imperative. If scoliosis is diagnosed, the school nurse can be a very effective contact in assisting the students by discussing exercise or brace care and by providing encouragement and general supportive help."}
{"id": "PMID:243112", "title": "Susceptibility to beta-lactam antibiotics and production of beta-lactamase in Bacteroides fragilis.", "content": "Using the agar dilution technique, 231 strains of Bacteroides fragilis, isolated during a 2-year period from human infections, were identified at subspecies level and were tested for susceptibility to 13 beta-lactam antibiotics. The penicillins were benzylpenicillin, ampicillin, carbenicillin, cloxacillin, and the recently described penicillin derivatives cyclacillin, ticarcillin, and PC-904. The following cephalosporin derivatives were tested: cephaloridine, cephalothin, cephalexin, cefamandole and cefuroxime. The cephamycin C derivative cefoxitin was also included in the study. Cefoxitin was the most effective drug tested since more than 80% of the strains were inhibited by 8 microgram/ml or less, and no strain had a minimal inhibitory concentration (MIC) of more than 64 microgram/ml. There was no marked difference in sensitivity among the subspecies with exception of subspecies vulgatus, which was slightly more sensitive to all antibiotics tested. The size of the inoculum was an important factor for obtaining reproducible results in the sensitivity tests. Increased inocula resulted in markedly higher MICs for cephaloridine and cefuroxime. Production of beta-lactamase was performed on all isolates by a chromogenic cephalosporin substrate and about 90% of the strains were found to be beta-lactamase producers.", "contents": "Susceptibility to beta-lactam antibiotics and production of beta-lactamase in Bacteroides fragilis. Using the agar dilution technique, 231 strains of Bacteroides fragilis, isolated during a 2-year period from human infections, were identified at subspecies level and were tested for susceptibility to 13 beta-lactam antibiotics. The penicillins were benzylpenicillin, ampicillin, carbenicillin, cloxacillin, and the recently described penicillin derivatives cyclacillin, ticarcillin, and PC-904. The following cephalosporin derivatives were tested: cephaloridine, cephalothin, cephalexin, cefamandole and cefuroxime. The cephamycin C derivative cefoxitin was also included in the study. Cefoxitin was the most effective drug tested since more than 80% of the strains were inhibited by 8 microgram/ml or less, and no strain had a minimal inhibitory concentration (MIC) of more than 64 microgram/ml. There was no marked difference in sensitivity among the subspecies with exception of subspecies vulgatus, which was slightly more sensitive to all antibiotics tested. The size of the inoculum was an important factor for obtaining reproducible results in the sensitivity tests. Increased inocula resulted in markedly higher MICs for cephaloridine and cefuroxime. Production of beta-lactamase was performed on all isolates by a chromogenic cephalosporin substrate and about 90% of the strains were found to be beta-lactamase producers."}
{"id": "PMID:243464", "title": "[Neuropsychological diagnosis and localization of brain lesions: their agreement with other examination visits (author's transl)].", "content": "Neuropsychological diagnoses were compared with those of clinical examination and the results of electro- and pneumoencephalography, angiography, brain-scan and with the final diagnoses in a random sample of 319 patients. A significant correspondence between neuropsychological findings and final diagnosis was found. The agreements were closer for the side than for the lobe of damage. The results indicate that the neuropsychological assessment usefully supplements other neurological methods in the diagnosis and localization of brain-damage.", "contents": "[Neuropsychological diagnosis and localization of brain lesions: their agreement with other examination visits (author's transl)]. Neuropsychological diagnoses were compared with those of clinical examination and the results of electro- and pneumoencephalography, angiography, brain-scan and with the final diagnoses in a random sample of 319 patients. A significant correspondence between neuropsychological findings and final diagnosis was found. The agreements were closer for the side than for the lobe of damage. The results indicate that the neuropsychological assessment usefully supplements other neurological methods in the diagnosis and localization of brain-damage."}
{"id": "PMID:243465", "title": "[The value of artificial respiration for patients with myasthenia gravis (author's transl)].", "content": "The value of artificial respiration for the bridging of crises in patients with myasthenia gravis is emphasized on some typical cases. Further use, beyond a life-saving indication, for limited periods is described. Such relative indications may exist, when there is not yet complete respiratory failure but when a worsening of myasthenic weakness or cholinergic intoxication may threaten a respiratory crisis. In order to prevent serious complications, early artificial respiration may be indicated in the following situations: deterioration of cardio-pulmonary complications, important changes in therapy, particularly at the start of immuno-suppressive treatment, following tracheobronchial aspiration, in chronic cholinergic intoxication, following operations under general anesthesia, particularly after thymectomy. The importance of careful psychotherapy of myasthenics threatened by respiratory crises and the well-timed information on the chances, intentions and goals of intensive care including artificial respiration is emphasized.", "contents": "[The value of artificial respiration for patients with myasthenia gravis (author's transl)]. The value of artificial respiration for the bridging of crises in patients with myasthenia gravis is emphasized on some typical cases. Further use, beyond a life-saving indication, for limited periods is described. Such relative indications may exist, when there is not yet complete respiratory failure but when a worsening of myasthenic weakness or cholinergic intoxication may threaten a respiratory crisis. In order to prevent serious complications, early artificial respiration may be indicated in the following situations: deterioration of cardio-pulmonary complications, important changes in therapy, particularly at the start of immuno-suppressive treatment, following tracheobronchial aspiration, in chronic cholinergic intoxication, following operations under general anesthesia, particularly after thymectomy. The importance of careful psychotherapy of myasthenics threatened by respiratory crises and the well-timed information on the chances, intentions and goals of intensive care including artificial respiration is emphasized."}
{"id": "PMID:243467", "title": "[The two languages of psychiatry (author's transl)].", "content": "Psychiatrists still use two languages, that of the \"Geisteswissenschaften\" (humanities) and that of the sciences. This has often led to a disregard of the differences between understanding and explanation, to a \"Sprachverwirrung\" (linguistic confusion), or to taking either understanding or explanation as absolute which leads to the formation of closed, ideology-like systems. As a result of the continued necessity for methodological pluralism, it is precisely by observing methodological limitations, that we have the current possibilities for bringing the \"Geisteswissenschaften\" (humanities) and the sciences, psychology and physiology closer to each other.", "contents": "[The two languages of psychiatry (author's transl)]. Psychiatrists still use two languages, that of the \"Geisteswissenschaften\" (humanities) and that of the sciences. This has often led to a disregard of the differences between understanding and explanation, to a \"Sprachverwirrung\" (linguistic confusion), or to taking either understanding or explanation as absolute which leads to the formation of closed, ideology-like systems. As a result of the continued necessity for methodological pluralism, it is precisely by observing methodological limitations, that we have the current possibilities for bringing the \"Geisteswissenschaften\" (humanities) and the sciences, psychology and physiology closer to each other."}
{"id": "PMID:243469", "title": "[The time-structure of a manic-depressive psychosis (author's transl)].", "content": "Some ideas about the desynchronisation and the restabilisation of the diurnal time-structure in the mood-and-drive system are the background for some hypotheses about the determination of the course and the theory of mixed states of manic-depressive psychoses. A model given in graphs is compared with empiric material from a typical casus, which could be shown with its prodrom and some weeks of its course. The structure of dimensionality was studied by factor-analysis, the time structure was studied by autocorrelation technique. A development of the chronobiological theory seems to be of interest.", "contents": "[The time-structure of a manic-depressive psychosis (author's transl)]. Some ideas about the desynchronisation and the restabilisation of the diurnal time-structure in the mood-and-drive system are the background for some hypotheses about the determination of the course and the theory of mixed states of manic-depressive psychoses. A model given in graphs is compared with empiric material from a typical casus, which could be shown with its prodrom and some weeks of its course. The structure of dimensionality was studied by factor-analysis, the time structure was studied by autocorrelation technique. A development of the chronobiological theory seems to be of interest."}
{"id": "PMID:243540", "title": "Dielectric dispersion of DL-alpha-valine in aqueous solution.", "content": "The complex permittivity (epsilon = epsilon - jepsilon) of an (0.5 M) aqueous solution of DL-alpha-valine was measured at microwave frequencies over the temperature range 0.3 - 40 degrees C. The magnitude and relaxation time of the dispersions were determined, and the results interpreted in terms of the molecular structure of the valine molecule in solution. The peak in the dielectric loss due to the relaxation of the valine molecules occurs at approximately 2.6 GHz at 37 degrees C.", "contents": "Dielectric dispersion of DL-alpha-valine in aqueous solution. The complex permittivity (epsilon = epsilon - jepsilon) of an (0.5 M) aqueous solution of DL-alpha-valine was measured at microwave frequencies over the temperature range 0.3 - 40 degrees C. The magnitude and relaxation time of the dispersions were determined, and the results interpreted in terms of the molecular structure of the valine molecule in solution. The peak in the dielectric loss due to the relaxation of the valine molecules occurs at approximately 2.6 GHz at 37 degrees C."}
{"id": "PMID:243541", "title": "Modification of repair of X-irradiation damage of hemopoietic system of mice by microwaves.", "content": "Microwaves (2450 tmhz, 10e mW/cm2, 300 s) were used to modify X-irradiation damage of the hemopoietic system in the mouse. Compared with X-irradiated controls, microwave-treated mice manifested an increased number of surviving hemopoietic stem cells, heightened erythropoiesis and myelopoiesis and increased rate of survival.", "contents": "Modification of repair of X-irradiation damage of hemopoietic system of mice by microwaves. Microwaves (2450 tmhz, 10e mW/cm2, 300 s) were used to modify X-irradiation damage of the hemopoietic system in the mouse. Compared with X-irradiated controls, microwave-treated mice manifested an increased number of surviving hemopoietic stem cells, heightened erythropoiesis and myelopoiesis and increased rate of survival."}
{"id": "PMID:243542", "title": "Rat lymphocytes in cell culture exposed to 2450 MHz (CW) microwave radiation.", "content": "Rat lymphocytes were exposed to continuous wave microwave radiation at a frequency of 2450 MHz at intensities of 5, 10 and 20 mW/cm2. The corresponding rates of absorption of energy were determined to be 0.7, 1.4 and 2.8 mW/g. The lymphocytes were exposed for 4, 24 or 44 h either with or without the addition of a mitogen (phytohemagglutinin). The transformation of lymphocytes into lyphoblasts was monitored by the addition of tritiated thymidine. No significant differences (P less than .05) were found in the uptake of tritiated thymidine between exposed and control cultures.", "contents": "Rat lymphocytes in cell culture exposed to 2450 MHz (CW) microwave radiation. Rat lymphocytes were exposed to continuous wave microwave radiation at a frequency of 2450 MHz at intensities of 5, 10 and 20 mW/cm2. The corresponding rates of absorption of energy were determined to be 0.7, 1.4 and 2.8 mW/g. The lymphocytes were exposed for 4, 24 or 44 h either with or without the addition of a mitogen (phytohemagglutinin). The transformation of lymphocytes into lyphoblasts was monitored by the addition of tritiated thymidine. No significant differences (P less than .05) were found in the uptake of tritiated thymidine between exposed and control cultures."}
{"id": "PMID:243543", "title": "Induced EM fields inside human bodies irradiated by EM waves of up to 500 MHz.", "content": "In this paper, the internal EM field and the specific absorption rate of EM energy induced inside human bodies by EM waves of up to 500 MHz are theoretically quantified based on a tensor integral equation method. Numerical results for a realistic model of a man of 177 cm high irradiated by EM waves of various frequencies and of vertical and horizontal polarizations are presented. The resonance phenomenon and the effect of body heterogeneity on the induced field are studied. Some theoretical results are compared with existing experimental results.", "contents": "Induced EM fields inside human bodies irradiated by EM waves of up to 500 MHz. In this paper, the internal EM field and the specific absorption rate of EM energy induced inside human bodies by EM waves of up to 500 MHz are theoretically quantified based on a tensor integral equation method. Numerical results for a realistic model of a man of 177 cm high irradiated by EM waves of various frequencies and of vertical and horizontal polarizations are presented. The resonance phenomenon and the effect of body heterogeneity on the induced field are studied. Some theoretical results are compared with existing experimental results."}
{"id": "PMID:243684", "title": "Adolescent sexuality in the Soviet Union--a personal perspective.", "content": "Russian pediatricians, psychiatrists, nurses, and midwives believe that adolescent sex education belongs in the home. Soviet society then has the responsibility of reinforcing the standards and attitudes instilled by the parents. The markedly puritanical sexual standards in Russia are similar to those seen in the United States at the turn of the century.", "contents": "Adolescent sexuality in the Soviet Union--a personal perspective. Russian pediatricians, psychiatrists, nurses, and midwives believe that adolescent sex education belongs in the home. Soviet society then has the responsibility of reinforcing the standards and attitudes instilled by the parents. The markedly puritanical sexual standards in Russia are similar to those seen in the United States at the turn of the century."}
{"id": "PMID:243792", "title": "Preexisting correlates of hospital stress.", "content": "More than 450 general medical and surgical patients were surveyed as part of an ongoing study of psychosocial factors in illness. Patients completed the Social Readjustment Rating Scale (Holmes and Rahe, 1967) as a measure of life stress prior to hospitalization and a hospital stress rating scale as a measure of hospital stress. Additional data included demographic variables, information about prior hospitalizations, and diagnosis, coded according to the Seriousness of Illness Rating Scale (Wyler et al., 1968). Analysis using multiple regression procedures indicated age (negatively) and life stress (positively) as predictors of hospital stress, for both medical and surgical patients. In addition, for medical patients, recency of previous hospitalization was a significant predictor of hospital stress, those with recent hospitalization reporting more stress than others. For surgical patients, those with serious illnesses reported more stress than others, and women reported more stress than men. Results revealed several preexisting correlates of hospital stress that can be easily identified at the time of hospital admission.", "contents": "Preexisting correlates of hospital stress. More than 450 general medical and surgical patients were surveyed as part of an ongoing study of psychosocial factors in illness. Patients completed the Social Readjustment Rating Scale (Holmes and Rahe, 1967) as a measure of life stress prior to hospitalization and a hospital stress rating scale as a measure of hospital stress. Additional data included demographic variables, information about prior hospitalizations, and diagnosis, coded according to the Seriousness of Illness Rating Scale (Wyler et al., 1968). Analysis using multiple regression procedures indicated age (negatively) and life stress (positively) as predictors of hospital stress, for both medical and surgical patients. In addition, for medical patients, recency of previous hospitalization was a significant predictor of hospital stress, those with recent hospitalization reporting more stress than others. For surgical patients, those with serious illnesses reported more stress than others, and women reported more stress than men. Results revealed several preexisting correlates of hospital stress that can be easily identified at the time of hospital admission."}
{"id": "PMID:243794", "title": "Alcoholic cardiomyopathy: a nursing approach.", "content": "When frequent hospital admissions of patients with acute congestive heart failure who also had alcoholic cardiomyopathy were observed at John Cochran Veterans Administration Hospital, St. Louis, Missouri, nursing interventions were developed in an effort not only to reduce the frequency of hospitalizations but also to improve the patient's clinical condition. Over an 18-month period, 26 patients with alcoholic cardiomyopathy were followed in a modified bedrest program in the patients' homes. The program was individualized, based on each patient's stage of cardiomyopathy. Agressive nursing interventions reversed significantly (p less than .01) the condition in 14 patients. These patients' recovery prompted a one-year follow-up with continuing close medical and nursing support. Data showed significant (p less than .01) positive findings one year later.", "contents": "Alcoholic cardiomyopathy: a nursing approach. When frequent hospital admissions of patients with acute congestive heart failure who also had alcoholic cardiomyopathy were observed at John Cochran Veterans Administration Hospital, St. Louis, Missouri, nursing interventions were developed in an effort not only to reduce the frequency of hospitalizations but also to improve the patient's clinical condition. Over an 18-month period, 26 patients with alcoholic cardiomyopathy were followed in a modified bedrest program in the patients' homes. The program was individualized, based on each patient's stage of cardiomyopathy. Agressive nursing interventions reversed significantly (p less than .01) the condition in 14 patients. These patients' recovery prompted a one-year follow-up with continuing close medical and nursing support. Data showed significant (p less than .01) positive findings one year later."}
{"id": "PMID:243796", "title": "Relationship of perceived empathy to nurses' communication.", "content": "Relationship between empathy as perceived by a helpee and the communication of a helper in a therapeutic encounter was investigated in an exploratory, descriptive analysis of verbal and vocal communicative behaviors of nurses. A stimulation was designed whereby a nurse interacted with an actress role playing the part of a patient in a physician's office. Overall verbal and vocal behaviors of high empathizers did not differ from verbal and vocal behaviors of low empathizers. A broad theoretical model of the perception of empathy is suggested, one incorporating all three channels of communication (verbal nonverbal, and vocal) and accounting for the congruency among these channels.", "contents": "Relationship of perceived empathy to nurses' communication. Relationship between empathy as perceived by a helpee and the communication of a helper in a therapeutic encounter was investigated in an exploratory, descriptive analysis of verbal and vocal communicative behaviors of nurses. A stimulation was designed whereby a nurse interacted with an actress role playing the part of a patient in a physician's office. Overall verbal and vocal behaviors of high empathizers did not differ from verbal and vocal behaviors of low empathizers. A broad theoretical model of the perception of empathy is suggested, one incorporating all three channels of communication (verbal nonverbal, and vocal) and accounting for the congruency among these channels."}
{"id": "PMID:243795", "title": "Faculty consensus as a socializing agent in professional education.", "content": "To assess the effectiveness of the professional socialization process in a professional school, this study focused on emerging attitueds of nursing students, perceived limits of their role, nursing autonomy, and rights of patients. Student attitudes were compared to attitudes of instructors to determine if socialization was taking place. Consensus among student attitudes was found to increase during the educational program, and attitudes of nursing students did approach those of their instructors. Degree of faculty consensus was suggested as a major determinant of the effectiveness of the socialization process in professional schools.", "contents": "Faculty consensus as a socializing agent in professional education. To assess the effectiveness of the professional socialization process in a professional school, this study focused on emerging attitueds of nursing students, perceived limits of their role, nursing autonomy, and rights of patients. Student attitudes were compared to attitudes of instructors to determine if socialization was taking place. Consensus among student attitudes was found to increase during the educational program, and attitudes of nursing students did approach those of their instructors. Degree of faculty consensus was suggested as a major determinant of the effectiveness of the socialization process in professional schools."}
{"id": "PMID:243797", "title": "Predicting infant apgar scores.", "content": "This study identified psychologic and sociologic phenomena that affect a woman during pregnancy which, when associated with physical factors, result in poor neonatal outcome for the infant, as measured by the Apgar score at five minutes after birth. The Utah Test Appraising Health (UTAH) was administered to 51 pregnant women during the second or third trimester of pregnancy. Data measuring maternal and infant outcomes were collected postdelivery. A significant correlation was found between maternal stress up to six months before administration of the UTAH questionnaire and the five-minute infant Apgar score (r = -.2787, p less than or equal to .05). The stress score was combined with past pregnancy complications, pregnancy symptoms during the first and third trimesters, and illness-proneness in a regression equation. The total multiple correlation coefficient was .8979, with stress X past pregnancy complications contributing most to the prediction equation. When stress and past pregnancy complications were controlled, the partial correlation value was -.8001. The data were consistent with the hypothesis that stress during pregnancy is an activator of physical illness processes in the mother, and, when combined with these variables, is related to neonatal outcome, as measured by the infant Apgar score at five minutes.", "contents": "Predicting infant apgar scores. This study identified psychologic and sociologic phenomena that affect a woman during pregnancy which, when associated with physical factors, result in poor neonatal outcome for the infant, as measured by the Apgar score at five minutes after birth. The Utah Test Appraising Health (UTAH) was administered to 51 pregnant women during the second or third trimester of pregnancy. Data measuring maternal and infant outcomes were collected postdelivery. A significant correlation was found between maternal stress up to six months before administration of the UTAH questionnaire and the five-minute infant Apgar score (r = -.2787, p less than or equal to .05). The stress score was combined with past pregnancy complications, pregnancy symptoms during the first and third trimesters, and illness-proneness in a regression equation. The total multiple correlation coefficient was .8979, with stress X past pregnancy complications contributing most to the prediction equation. When stress and past pregnancy complications were controlled, the partial correlation value was -.8001. The data were consistent with the hypothesis that stress during pregnancy is an activator of physical illness processes in the mother, and, when combined with these variables, is related to neonatal outcome, as measured by the infant Apgar score at five minutes."}
{"id": "PMID:243793", "title": "Nurse perceptions of patient characteristics.", "content": "To determine whether nurse perceptions of patients are influenced by a patient's socioeconomic class, 78 nurse subjects observed slides and read about a patient and then rated him on a seven-point scale. Nurses were randomly given one of eight written descriptions in which the patient was identified as middle or lower class., with a more or a less serious and a more or a less socially acceptable illness. Results were subjected to 2 X 2 X 2 analysis of variance. Nurses were found to stereotype lower-class patients as dependent, passive, unintelligent, noncomprehending, ummotivated, lazy, forgetful, inaccurate, careless, uninformed, unsuccessful, and unreliable. Patients with less-acceptable illnesses were rated more negatively than those with more-acceptable illnesses and were perceived as sensitive, rigid, bored, and resistant to learning about their illness. Since nurses admitted they would feel embarrassed and would conceal having these less-acceptable illnesses themselves, these negative perceptions of patients may be projections of the nurses' feelings.", "contents": "Nurse perceptions of patient characteristics. To determine whether nurse perceptions of patients are influenced by a patient's socioeconomic class, 78 nurse subjects observed slides and read about a patient and then rated him on a seven-point scale. Nurses were randomly given one of eight written descriptions in which the patient was identified as middle or lower class., with a more or a less serious and a more or a less socially acceptable illness. Results were subjected to 2 X 2 X 2 analysis of variance. Nurses were found to stereotype lower-class patients as dependent, passive, unintelligent, noncomprehending, ummotivated, lazy, forgetful, inaccurate, careless, uninformed, unsuccessful, and unreliable. Patients with less-acceptable illnesses were rated more negatively than those with more-acceptable illnesses and were perceived as sensitive, rigid, bored, and resistant to learning about their illness. Since nurses admitted they would feel embarrassed and would conceal having these less-acceptable illnesses themselves, these negative perceptions of patients may be projections of the nurses' feelings."}
{"id": "PMID:243798", "title": "Nursing students' attitudes toward death.", "content": "This descriptive study tested: 1) whether a change in attitude toward death and the dying was associated with the clinical course. \"Nursing of the Adult Patient with Malignant Neoplastic Disease,\" and 2) the validity and reliability of the questionnaire. Death Attitude Indicator. Data were collected by pre- and posttesting 40 senior nursing students, half of whom had elected to take the course, within the interval of one semester. Results showed no change in attitude in either group conflicting data raised a question of whether the two groups began the study with similar attitudes toward death. Two factors were found to be associated with the respondent's score on the questionnarie: experience with a family death and indication of a belief in a Supreme Being.", "contents": "Nursing students' attitudes toward death. This descriptive study tested: 1) whether a change in attitude toward death and the dying was associated with the clinical course. \"Nursing of the Adult Patient with Malignant Neoplastic Disease,\" and 2) the validity and reliability of the questionnaire. Death Attitude Indicator. Data were collected by pre- and posttesting 40 senior nursing students, half of whom had elected to take the course, within the interval of one semester. Results showed no change in attitude in either group conflicting data raised a question of whether the two groups began the study with similar attitudes toward death. Two factors were found to be associated with the respondent's score on the questionnarie: experience with a family death and indication of a belief in a Supreme Being."}
{"id": "PMID:243800", "title": "Effectiveness of a programmed instruction module on oral contraceptives.", "content": "To determine effectiveness of a programmed instruction module (PIM) on oral contraceptives, during their obstetric experience 34 nursing students in the Department of Nursing at the California State University, Long Beach, were assigned to three groups, two experimental groups and one control group. In the first experimental group 12 students worked independently, at their own pace, using a PIM developed by the investigator. In the second experimental group the investigator taught 11 students the same content by the lecture-discussion (LD) method. For comparison purposes, a third group of 11 students (control) received their instruction on the topic via regular classroom teaching. No significant difference was found between the PIM AND LD groups. However, a significant (p less than .01) gain in knowledge regarding oral contraceptives was found when these two groups were compared to the regular classroom instruction group. In addition, over half of the students who used the PIM preferred this method of teaching.", "contents": "Effectiveness of a programmed instruction module on oral contraceptives. To determine effectiveness of a programmed instruction module (PIM) on oral contraceptives, during their obstetric experience 34 nursing students in the Department of Nursing at the California State University, Long Beach, were assigned to three groups, two experimental groups and one control group. In the first experimental group 12 students worked independently, at their own pace, using a PIM developed by the investigator. In the second experimental group the investigator taught 11 students the same content by the lecture-discussion (LD) method. For comparison purposes, a third group of 11 students (control) received their instruction on the topic via regular classroom teaching. No significant difference was found between the PIM AND LD groups. However, a significant (p less than .01) gain in knowledge regarding oral contraceptives was found when these two groups were compared to the regular classroom instruction group. In addition, over half of the students who used the PIM preferred this method of teaching."}
{"id": "PMID:243801", "title": "Nurse encounters with dying and nondying patients.", "content": "In measuring duration of nurse encounters with dying and nondying patients, 22 staff nurses were observed for a two-hour period; the duration of all encounters was measured with a stop-watch. The prognosis of each patient was classified by the investigators and the observed nurses. Statistical analysis revealed that when the prognosis was classified according to the investigator's definition, nurses spent significantly more time with dying than with nondying patients. The nurse's verbal acknowledgment of the patient's dying status had no effect on the duration of the encounter. The proportion of time the nurse spent in meeting emotional needs was not affected by terminal prognosis as classified by the investigators or the nurses.", "contents": "Nurse encounters with dying and nondying patients. In measuring duration of nurse encounters with dying and nondying patients, 22 staff nurses were observed for a two-hour period; the duration of all encounters was measured with a stop-watch. The prognosis of each patient was classified by the investigators and the observed nurses. Statistical analysis revealed that when the prognosis was classified according to the investigator's definition, nurses spent significantly more time with dying than with nondying patients. The nurse's verbal acknowledgment of the patient's dying status had no effect on the duration of the encounter. The proportion of time the nurse spent in meeting emotional needs was not affected by terminal prognosis as classified by the investigators or the nurses."}
{"id": "PMID:243799", "title": "A statistical method for development of subconcepts in nursing.", "content": "Achievement tests, whether cognitive or performance, often are not analyzed with the intent of detecting subtests within the total test. Subtests should represent unitary concepts. A step-by-step process for detecting subconcepts is proposed and exemplified. Concepts arrived at by the proposed methodology can provide insight to learner strategies for learning and can refine outcome measures to detect effects of the independent variable in teaching-learning investigations.", "contents": "A statistical method for development of subconcepts in nursing. Achievement tests, whether cognitive or performance, often are not analyzed with the intent of detecting subtests within the total test. Subtests should represent unitary concepts. A step-by-step process for detecting subconcepts is proposed and exemplified. Concepts arrived at by the proposed methodology can provide insight to learner strategies for learning and can refine outcome measures to detect effects of the independent variable in teaching-learning investigations."}
{"id": "PMID:243906", "title": "Thrombophlebitis. Prevention, recognition, and management.", "content": "Thrombophlebitis is a common disease entity with characteristic features of edema, inflammation, and tenderness. If the disease process is extensive, the postphlebitic syndrome, which is characterized by persistent edema, pigmentation, dermatitis, ulceration, and varicose veins, invariably occurs.", "contents": "Thrombophlebitis. Prevention, recognition, and management. Thrombophlebitis is a common disease entity with characteristic features of edema, inflammation, and tenderness. If the disease process is extensive, the postphlebitic syndrome, which is characterized by persistent edema, pigmentation, dermatitis, ulceration, and varicose veins, invariably occurs."}
{"id": "PMID:243907", "title": "Appropriate use of psychotropic drugs in physical illness.", "content": "Psychotropic drugs have a useful place as an adjunct to the treatment of patients with certain categories of physical illness, but must never substitute for an integrated and coherent approach to the patient.", "contents": "Appropriate use of psychotropic drugs in physical illness. Psychotropic drugs have a useful place as an adjunct to the treatment of patients with certain categories of physical illness, but must never substitute for an integrated and coherent approach to the patient."}
{"id": "PMID:243908", "title": "Urinary tract infections.", "content": "Urinary tract infections can be found in either sex at any age. While the majority occur in adult females as acute cystitis, recurrent symptomatic bacteriuria, or asymptomatic bacteriuria, adult males with prostatitis or acute pyelonephritis and children with symptomatic urinary tract infections comprise a considerable portion of patients seen. Management in pregnant females or in males with indwelling catheters or before prostatic surgery presents special problems. The choice of drug and dosage schedule should vary according to the infecting agent and the clinical state of the patient.", "contents": "Urinary tract infections. Urinary tract infections can be found in either sex at any age. While the majority occur in adult females as acute cystitis, recurrent symptomatic bacteriuria, or asymptomatic bacteriuria, adult males with prostatitis or acute pyelonephritis and children with symptomatic urinary tract infections comprise a considerable portion of patients seen. Management in pregnant females or in males with indwelling catheters or before prostatic surgery presents special problems. The choice of drug and dosage schedule should vary according to the infecting agent and the clinical state of the patient."}
{"id": "PMID:243909", "title": "Exercise and diabetic control.", "content": "Exercise, an important component of good diabetic control, is often associated with hypoglycemia in insulin-treated patients. Understanding the mechanism of exercise-induced hypoglycemia and its relationship to the insulin injection site will be helpful in the management of diabetes.", "contents": "Exercise and diabetic control. Exercise, an important component of good diabetic control, is often associated with hypoglycemia in insulin-treated patients. Understanding the mechanism of exercise-induced hypoglycemia and its relationship to the insulin injection site will be helpful in the management of diabetes."}
{"id": "PMID:243910", "title": "Pregnancy and diabetes.", "content": "Pregnancy in the diabetic is no longer the universal tragedy for mother and child that it once was but avoidable fetal loss wil continue to occur unless gestational diabetes is detected, and unless meticulous control and monitoring of the insulin dependent diabetic is maintained. As Kinch has so succinctly stated \"careful composite chemical control oa cooperative patient\" is pivotal.", "contents": "Pregnancy and diabetes. Pregnancy in the diabetic is no longer the universal tragedy for mother and child that it once was but avoidable fetal loss wil continue to occur unless gestational diabetes is detected, and unless meticulous control and monitoring of the insulin dependent diabetic is maintained. As Kinch has so succinctly stated \"careful composite chemical control oa cooperative patient\" is pivotal."}
{"id": "PMID:243911", "title": "Assessment of psychiatric emergencies in medical practice.", "content": "Acute psychiatric emergencies, often encountered in medical practice, demand rapid evaluation and treatment; routine measures are not enough. A scheme for acutely assessing such crises is outlined, and some of the more common emergencies are discussed.", "contents": "Assessment of psychiatric emergencies in medical practice. Acute psychiatric emergencies, often encountered in medical practice, demand rapid evaluation and treatment; routine measures are not enough. A scheme for acutely assessing such crises is outlined, and some of the more common emergencies are discussed."}
{"id": "PMID:243912", "title": "What to expect from a psychiatric consultant.", "content": "A psychiatric consultant may clarify a confusing differential diagnosis, help explain and manage difficult psychological symptoms and behavioral problems, and can be useful in specific reactions to physical illness.", "contents": "What to expect from a psychiatric consultant. A psychiatric consultant may clarify a confusing differential diagnosis, help explain and manage difficult psychological symptoms and behavioral problems, and can be useful in specific reactions to physical illness."}
{"id": "PMID:243914", "title": "Hypoglycemia.", "content": "In the present review, we have tried to briefly define the types of hypoglycemia which may be seen most frequently in medicine. Wherever possible, mechanisms and appropriate diagnostic tests have been described. Treatment of hypoglycemia has been purposely avoided, since therapy should be obvious once diagnosis is made and mechanisms are understood. While it is recognized that this review is not exhaustive, it should cover over 95 per cent  of the cases of hypoglycemia encountered by the practicing physician.", "contents": "Hypoglycemia. In the present review, we have tried to briefly define the types of hypoglycemia which may be seen most frequently in medicine. Wherever possible, mechanisms and appropriate diagnostic tests have been described. Treatment of hypoglycemia has been purposely avoided, since therapy should be obvious once diagnosis is made and mechanisms are understood. While it is recognized that this review is not exhaustive, it should cover over 95 per cent  of the cases of hypoglycemia encountered by the practicing physician."}
{"id": "PMID:243915", "title": "Cystic fibrosis.", "content": "Cystic fibrosis has been regarded as a disease of infants. Yet, with improved management, a high percentage of patients how survive into young adulthood. In addition, mild cases may not be detected until long after infance. The older patient often has minimal symptoms, and the majority are socially active and  productive.", "contents": "Cystic fibrosis. Cystic fibrosis has been regarded as a disease of infants. Yet, with improved management, a high percentage of patients how survive into young adulthood. In addition, mild cases may not be detected until long after infance. The older patient often has minimal symptoms, and the majority are socially active and  productive."}
{"id": "PMID:243916", "title": "Manifestations of cystic fibrosis.", "content": "The diagnosis of cystic fibrosis is usually established by the presence of chronic obstructive lung disease and/or gastrointestinal compromise, together with elevated sweat electrolytes or pathologic changes in tissue. Because of its highly variable genetic penetrance, the disease is characterized by varying degrees of involvement of different exocrine systems.", "contents": "Manifestations of cystic fibrosis. The diagnosis of cystic fibrosis is usually established by the presence of chronic obstructive lung disease and/or gastrointestinal compromise, together with elevated sweat electrolytes or pathologic changes in tissue. Because of its highly variable genetic penetrance, the disease is characterized by varying degrees of involvement of different exocrine systems."}
{"id": "PMID:243917", "title": "Benign breast disease. Diagnosis and treatment.", "content": "Breast disease is a common problem found in approximately one of four women from puberty to old age. Of greatest importance to the health care provider is identifying the type of breast disorder and its relative seriousness. Precancerous mastopathy is of major concern, as are other significant forms of benign breast disease, both symptomatic and asymptomatic. Awareness of the many facets of benign breast disease on the part of the health care provider and the patient can heighten sensitivity to subtle changes in breast tissue. Identification of precancerous mastopathy has its greatest impact for early diagnosis of breast cancer. The patient with benign breast disease can be offered reassurance, support and symptomatic treatment for the benign breast disorder by the primary health care provider.", "contents": "Benign breast disease. Diagnosis and treatment. Breast disease is a common problem found in approximately one of four women from puberty to old age. Of greatest importance to the health care provider is identifying the type of breast disorder and its relative seriousness. Precancerous mastopathy is of major concern, as are other significant forms of benign breast disease, both symptomatic and asymptomatic. Awareness of the many facets of benign breast disease on the part of the health care provider and the patient can heighten sensitivity to subtle changes in breast tissue. Identification of precancerous mastopathy has its greatest impact for early diagnosis of breast cancer. The patient with benign breast disease can be offered reassurance, support and symptomatic treatment for the benign breast disorder by the primary health care provider."}
{"id": "PMID:243918", "title": "Detection of breast cancer. A practitioner's viewpoint.", "content": "Ultimate responsibility for the early diagnosis of breast cancer rests upon the front line or primary care physician, just as management decisions following diagnosis fall principally upon the surgeon, radiotherapist, and oncologist. The value of mammography as an effective screening test for the early detection of disease has been enthusiastically endorsed over the past several years on the basis of encouraging results of several studies. Serious reservations regarding the safety of mammography as a screening procedure have subsequently been raised. The practicing physician is faced with a serious problem of time lag in gathering information upon which to base clinical decisions. The purpose of this article is to review the pros and cons in the controversy over mammography so that informed decisions can be made on behalf of patients.", "contents": "Detection of breast cancer. A practitioner's viewpoint. Ultimate responsibility for the early diagnosis of breast cancer rests upon the front line or primary care physician, just as management decisions following diagnosis fall principally upon the surgeon, radiotherapist, and oncologist. The value of mammography as an effective screening test for the early detection of disease has been enthusiastically endorsed over the past several years on the basis of encouraging results of several studies. Serious reservations regarding the safety of mammography as a screening procedure have subsequently been raised. The practicing physician is faced with a serious problem of time lag in gathering information upon which to base clinical decisions. The purpose of this article is to review the pros and cons in the controversy over mammography so that informed decisions can be made on behalf of patients."}
{"id": "PMID:243919", "title": "Influenza. The continuing need and justification for immunization.", "content": "A review of some of the major questions regarding influenza immunization. New insights in influenza virology and the consequence of epidemic influenza. The reasons for past failure in immunization. The rationale for continuing immunization efforts in the \"post Swine-influenza\" era.", "contents": "Influenza. The continuing need and justification for immunization. A review of some of the major questions regarding influenza immunization. New insights in influenza virology and the consequence of epidemic influenza. The reasons for past failure in immunization. The rationale for continuing immunization efforts in the \"post Swine-influenza\" era."}
{"id": "PMID:243920", "title": "The mitotic activity of blood monocytes cultured in autologous wound fluid.", "content": "Wound fluid was obtained from the subcutaneous tissue of sheep by implanting a perforated Teflon sampling chamber. A catheter from this chamber was brought to the surface. The types and numbers of cells in this fluid were recorded. Cell free fluid was used at either 100% concentration, or 25% concentration in plasma, as a medium for the culture of autologous blood monocytes. Its ability to support mitosis was compared with that of 100% autologous plasma. Wound fluids taken upon consecutive post-implantation days were compared. Cultured monocytes survived in small numbers in wound fluid collected on the days immediately following operation. When mitosis occurred the mitotic indices remained low. The wound fluid did not exhibit that mitogenicity which is apparent in autologous plasma taken on the third or fourth days following implantation. The results suggest that, following the implantation of Teflon, the wound fluid contains a component which is toxic for blood monocytes cultured upon glass.", "contents": "The mitotic activity of blood monocytes cultured in autologous wound fluid. Wound fluid was obtained from the subcutaneous tissue of sheep by implanting a perforated Teflon sampling chamber. A catheter from this chamber was brought to the surface. The types and numbers of cells in this fluid were recorded. Cell free fluid was used at either 100% concentration, or 25% concentration in plasma, as a medium for the culture of autologous blood monocytes. Its ability to support mitosis was compared with that of 100% autologous plasma. Wound fluids taken upon consecutive post-implantation days were compared. Cultured monocytes survived in small numbers in wound fluid collected on the days immediately following operation. When mitosis occurred the mitotic indices remained low. The wound fluid did not exhibit that mitogenicity which is apparent in autologous plasma taken on the third or fourth days following implantation. The results suggest that, following the implantation of Teflon, the wound fluid contains a component which is toxic for blood monocytes cultured upon glass."}
{"id": "PMID:243921", "title": "The role of the autonomic nervous system in the depression of parotid salivary secretion during hyperkalaemia in conscious sheep.", "content": "The rate of flow and electrolyte concentration of parotid saliva were measured before, during and after intravenous and contralateral intracarotid infusion of KCl (0.5 mol.1(-1)) and NaCl (0.5 mol.1(-1)) at 385-625 mumol. min(-1) for 40 min into 5 sheep. In intact conscious sheep contralateral intracarotid infusion of KCl caused marked depression of salivary secretion in all experiments whereas infusion of NaCl had no consistent effect on flow. Intravenous infusion of KCl into the intact conscious sheep caused a slight depression of salivary secretion but minimum flow was significantly higher than that during intracarotid infusion. When the sheep were anaesthetized salivary flow rates were low and contralateral intracarotid infusion of KCl either had no effect on flow or caused an increase in flow. After ipsilateral cervical sympathectomy contralateral intracarotid infusion of KCl into the conscious sheep caused a marked depression of salivary flow similar to that occurring when the sheep were intact. After section of the secretomotor nerve of the gland salivary flow rates were low and contralateral intracarotid infusion of KC1 had no effect on flow. The salivary flow responses of the sheep were consistent, regardless of whether the KCl infusions were given within 24 h or 1-2 weeks after cervical sympathectomy or secretomotor nerve section. Salivary sodium concentration was negatively correlated with salivary flow in all experiments. It was concluded that potassium acted at a site located in the head but by direct action on the salivary gland. The depression of salivary secretion by hyperkalaemia resulted from a decline in neural activity in the parasympathetic secretomotor innervation of the parotid gland.", "contents": "The role of the autonomic nervous system in the depression of parotid salivary secretion during hyperkalaemia in conscious sheep. The rate of flow and electrolyte concentration of parotid saliva were measured before, during and after intravenous and contralateral intracarotid infusion of KCl (0.5 mol.1(-1)) and NaCl (0.5 mol.1(-1)) at 385-625 mumol. min(-1) for 40 min into 5 sheep. In intact conscious sheep contralateral intracarotid infusion of KCl caused marked depression of salivary secretion in all experiments whereas infusion of NaCl had no consistent effect on flow. Intravenous infusion of KCl into the intact conscious sheep caused a slight depression of salivary secretion but minimum flow was significantly higher than that during intracarotid infusion. When the sheep were anaesthetized salivary flow rates were low and contralateral intracarotid infusion of KCl either had no effect on flow or caused an increase in flow. After ipsilateral cervical sympathectomy contralateral intracarotid infusion of KCl into the conscious sheep caused a marked depression of salivary flow similar to that occurring when the sheep were intact. After section of the secretomotor nerve of the gland salivary flow rates were low and contralateral intracarotid infusion of KC1 had no effect on flow. The salivary flow responses of the sheep were consistent, regardless of whether the KCl infusions were given within 24 h or 1-2 weeks after cervical sympathectomy or secretomotor nerve section. Salivary sodium concentration was negatively correlated with salivary flow in all experiments. It was concluded that potassium acted at a site located in the head but by direct action on the salivary gland. The depression of salivary secretion by hyperkalaemia resulted from a decline in neural activity in the parasympathetic secretomotor innervation of the parotid gland."}
{"id": "PMID:243922", "title": "Influence of level of habitual activity on physical working capacity and body composition of post-puberal school boys.", "content": "The relationships between level of habitual activity, physical working capacity at a heart rate of 170 beats per minute (PWC170), % fat and body size, have been investigated in 85 post-puberal males aged 16 to 18. Percentage of fat was estimated from the sum of four skinfold thickness and body size characterized by: height and weight; arm, chest, calf and thigh circumferences; bicromial and bi-iliac diameters. PWC170 was found to be significantly related to level of habitual activity and to most measures of body size; multiple regression analysis indicates that level of habitual activity and size respectively account for 34% and 37% of the variance in PWC170. When differences in the body weight of the subjects were statistically removed, % fat was related positively to arm circumference, and negatively to height and bi-iliac diameter. There was no relationship between % fat and level of habitual activity. The significance of these results is discussed.", "contents": "Influence of level of habitual activity on physical working capacity and body composition of post-puberal school boys. The relationships between level of habitual activity, physical working capacity at a heart rate of 170 beats per minute (PWC170), % fat and body size, have been investigated in 85 post-puberal males aged 16 to 18. Percentage of fat was estimated from the sum of four skinfold thickness and body size characterized by: height and weight; arm, chest, calf and thigh circumferences; bicromial and bi-iliac diameters. PWC170 was found to be significantly related to level of habitual activity and to most measures of body size; multiple regression analysis indicates that level of habitual activity and size respectively account for 34% and 37% of the variance in PWC170. When differences in the body weight of the subjects were statistically removed, % fat was related positively to arm circumference, and negatively to height and bi-iliac diameter. There was no relationship between % fat and level of habitual activity. The significance of these results is discussed."}
{"id": "PMID:243923", "title": "The energy cost of locomotion on the level and on gradients for the red deer (Cervus elaphus).", "content": "The oxygen consumption (Vo2) of three castrated male red deer was measured while they walked on a treadmill at 7 degree and 14 degree slopes and on the level at speeds varying from 44.3 to 172.9 m.min(-1). The energy cost of horizontal locomotion in excess of standing was 2.6 J kg(-1).m(-1). The cost of maintenance of posture when walking was the same as that of standing. The energy cost of walking up gradients was 21.5 J kg(-1).vertical m(-1). These results are discussed in relation to values reported for other species.", "contents": "The energy cost of locomotion on the level and on gradients for the red deer (Cervus elaphus). The oxygen consumption (Vo2) of three castrated male red deer was measured while they walked on a treadmill at 7 degree and 14 degree slopes and on the level at speeds varying from 44.3 to 172.9 m.min(-1). The energy cost of horizontal locomotion in excess of standing was 2.6 J kg(-1).m(-1). The cost of maintenance of posture when walking was the same as that of standing. The energy cost of walking up gradients was 21.5 J kg(-1).vertical m(-1). These results are discussed in relation to values reported for other species."}
{"id": "PMID:243924", "title": "The effect of secretin and cholecystokinin-pancreozymin on the secretion of bile in the anaesthetized rabbit.", "content": "Effects of secretin and Cholecystokinin-Pancreozymin (CCK-PZ) on the secretion of bile in anaesthetized rabbits have been studied. Single injections of secretin (5.0 u.kg(-1) significantly increased the flow of bile irrespectively of whether the cystic duct was free or had been tied. A sustained increase in bile flow could be obtained by the continuous infusion of secretin. Cholecystokinin-Pancreozymin was effective in increasing the bile flow in doses of 1.0 u.kg(-1). Much of the effect could be attributed to contraction of the gallbladder but a significant increase in flow could still be elicited after ligation of the cystic duct. Our findings strongly suggest that the biliary secretion in rabbits is not as different from the general pattern as has previously been suggested.", "contents": "The effect of secretin and cholecystokinin-pancreozymin on the secretion of bile in the anaesthetized rabbit. Effects of secretin and Cholecystokinin-Pancreozymin (CCK-PZ) on the secretion of bile in anaesthetized rabbits have been studied. Single injections of secretin (5.0 u.kg(-1) significantly increased the flow of bile irrespectively of whether the cystic duct was free or had been tied. A sustained increase in bile flow could be obtained by the continuous infusion of secretin. Cholecystokinin-Pancreozymin was effective in increasing the bile flow in doses of 1.0 u.kg(-1). Much of the effect could be attributed to contraction of the gallbladder but a significant increase in flow could still be elicited after ligation of the cystic duct. Our findings strongly suggest that the biliary secretion in rabbits is not as different from the general pattern as has previously been suggested."}
{"id": "PMID:243955", "title": "Effects of Ro 4-1284 on electrically-induced spinal cord seizures and on spinal cord norepinephrine and 5-hydroxytryptamine levels.", "content": "The time course effects of the benzoquinolizine Ro 4-1284 on spinal cord norepinephrine (NE) and 5-hydroxytryptamine (5-HT) levels were compared to the effects of this same drug on electrically-induced spinal cord seizures. The data show that a significant decrease in spinal cord NE levels and a facilitating effect on spinal cord seizures are apparent 15 minutes after Ro 4-1284 (10 mg/kg s.c.) and that both of these effects persist for at least 24 hours. Forty-eight hours after injection, the effects of Ro 4-1284 on seizure and on NE levels are completely dissipated. A significant decrease in 5-HT levels is not apparent until 1 hour after Ro 4-1284. These data suggest that noradrenergic neurons of the spinal cord act as attenuators of seizure activity. The possibility that spinal cord 5-HT also subserves a seizure attenuating function is not precluded.", "contents": "Effects of Ro 4-1284 on electrically-induced spinal cord seizures and on spinal cord norepinephrine and 5-hydroxytryptamine levels. The time course effects of the benzoquinolizine Ro 4-1284 on spinal cord norepinephrine (NE) and 5-hydroxytryptamine (5-HT) levels were compared to the effects of this same drug on electrically-induced spinal cord seizures. The data show that a significant decrease in spinal cord NE levels and a facilitating effect on spinal cord seizures are apparent 15 minutes after Ro 4-1284 (10 mg/kg s.c.) and that both of these effects persist for at least 24 hours. Forty-eight hours after injection, the effects of Ro 4-1284 on seizure and on NE levels are completely dissipated. A significant decrease in 5-HT levels is not apparent until 1 hour after Ro 4-1284. These data suggest that noradrenergic neurons of the spinal cord act as attenuators of seizure activity. The possibility that spinal cord 5-HT also subserves a seizure attenuating function is not precluded."}
{"id": "PMID:244310", "title": "The dynamics of trends in drug use in Australia.", "content": "Drug use tends to follow cycles. Monitoring may be used to establish the trends over time and to analyse their dynamics. An approach is described which establishes the stage of adoption or discontinuance of drug use in the community and a method for the prediction of future trends. Monitoring in New South Wales from 1971 to 1973 provided data which are analysed to show that alcohol was in the phase of majority adoption and tobacco had reached a plateau, but with the worrying anomaly that heavy use among young people continued to rise. Sedatives and analgesics had also reached a plateau stage of use. The data on marijuana are subject to more than one interpretation, but in any case point to a continuing rapid increase in use; predictions are made about future trends. Hallucinogens seemed to be in the phase of late adoption and stimulants to have entered a phase that is of particular interest, discontinuance. Narcotics seemed to be in the phase of late majority adoption.", "contents": "The dynamics of trends in drug use in Australia. Drug use tends to follow cycles. Monitoring may be used to establish the trends over time and to analyse their dynamics. An approach is described which establishes the stage of adoption or discontinuance of drug use in the community and a method for the prediction of future trends. Monitoring in New South Wales from 1971 to 1973 provided data which are analysed to show that alcohol was in the phase of majority adoption and tobacco had reached a plateau, but with the worrying anomaly that heavy use among young people continued to rise. Sedatives and analgesics had also reached a plateau stage of use. The data on marijuana are subject to more than one interpretation, but in any case point to a continuing rapid increase in use; predictions are made about future trends. Hallucinogens seemed to be in the phase of late adoption and stimulants to have entered a phase that is of particular interest, discontinuance. Narcotics seemed to be in the phase of late majority adoption."}
{"id": "PMID:244313", "title": "The human urinary excretion pattern of morphine and codeine following the consumption of morphine, opium, codeine and heroin.", "content": "The urinary excretion patterns of morphine and codeine in a number of individuals following consumption of morphine-based narcotic drugs have been studied. From the data collected the relative amounts of codeine and morphine in urine specimens were compared and certain trends, consistencies and irregularities were revealed. To a certain extent, the ratio of the proportion of codeine to morphine excretion in urine may be used to determine the nature of the drugs consumed. This correlation is useful in the interpretation of the results of urine analysis which is the basis of effective control and rehabilitation of drug addiction.", "contents": "The human urinary excretion pattern of morphine and codeine following the consumption of morphine, opium, codeine and heroin. The urinary excretion patterns of morphine and codeine in a number of individuals following consumption of morphine-based narcotic drugs have been studied. From the data collected the relative amounts of codeine and morphine in urine specimens were compared and certain trends, consistencies and irregularities were revealed. To a certain extent, the ratio of the proportion of codeine to morphine excretion in urine may be used to determine the nature of the drugs consumed. This correlation is useful in the interpretation of the results of urine analysis which is the basis of effective control and rehabilitation of drug addiction."}
{"id": "PMID:244316", "title": "Flail chest as a complication of cardiopulmonary resuscitation.", "content": "Records of all patients who developed flail chest after cardiopulmonary resuscitation at Rochester Methodist Hospital between January, 1966 and March 1976 were reviewed. Also, for comparison, records of patients with flail chest resulting from motor vehicle accidents and those of a matched group of patients who underwent cardiopulmonary resuscitation without developing flail chest were reviewed. The incidence of flail chest after cardiopulmonary resuscitation was about 5.6 per 100 survivors. The groups who did and did not have flail chest after cardiopulmonary resuscitation were alike in age and in frequency and duration of the resuscitation. Stabilization of the flail chest required mechanical ventilation for 1 to 24 days (mean, 10.7). Flail chest did not significantly lengthen the hospitalization of patients who survived after cardiopulmonary resuscitation. The occurrence of flail chest after cardiopulmonary resuscitation did not seem to increase the mortality rate.", "contents": "Flail chest as a complication of cardiopulmonary resuscitation. Records of all patients who developed flail chest after cardiopulmonary resuscitation at Rochester Methodist Hospital between January, 1966 and March 1976 were reviewed. Also, for comparison, records of patients with flail chest resulting from motor vehicle accidents and those of a matched group of patients who underwent cardiopulmonary resuscitation without developing flail chest were reviewed. The incidence of flail chest after cardiopulmonary resuscitation was about 5.6 per 100 survivors. The groups who did and did not have flail chest after cardiopulmonary resuscitation were alike in age and in frequency and duration of the resuscitation. Stabilization of the flail chest required mechanical ventilation for 1 to 24 days (mean, 10.7). Flail chest did not significantly lengthen the hospitalization of patients who survived after cardiopulmonary resuscitation. The occurrence of flail chest after cardiopulmonary resuscitation did not seem to increase the mortality rate."}
{"id": "PMID:244317", "title": "Masking of exercise-induced ST-segment depression by rate-dependent left-axis deviation.", "content": "An unexpected high incidence of false negative ST-segment responses to exercise was previously reported for patients with coronary artery disease and abnormal left-axis deviation on their resting electrocardiograms. In the case presented, an exercise-induced, \"ischemia\" ST-segment depression was masked with the onset of rate-dependent left-axis deviation. The state of the base-line electrocardiogram is an important but often overlooked factor in assessing the incidence of false negative and false positive ST-segment responses to exercise.", "contents": "Masking of exercise-induced ST-segment depression by rate-dependent left-axis deviation. An unexpected high incidence of false negative ST-segment responses to exercise was previously reported for patients with coronary artery disease and abnormal left-axis deviation on their resting electrocardiograms. In the case presented, an exercise-induced, \"ischemia\" ST-segment depression was masked with the onset of rate-dependent left-axis deviation. The state of the base-line electrocardiogram is an important but often overlooked factor in assessing the incidence of false negative and false positive ST-segment responses to exercise."}
{"id": "PMID:244323", "title": "Arterial blood gases in the coronary care unit. Part IV.", "content": "An acute MI complicating advanced COPD is an unusual clinical occurrence. Nevertheless, when these diseases coexist the appropriate use of blood gas analysis and the appreciation of their inherent problems will improve the prognosis. This vignette attempts to point out these problems and their management.", "contents": "Arterial blood gases in the coronary care unit. Part IV. An acute MI complicating advanced COPD is an unusual clinical occurrence. Nevertheless, when these diseases coexist the appropriate use of blood gas analysis and the appreciation of their inherent problems will improve the prognosis. This vignette attempts to point out these problems and their management."}
{"id": "PMID:244331", "title": "Streptomycin and sulfisoxazole for treatment of Haemophilus influenzae meningitis.", "content": "The increasing number of ampicillin-resistant Haemophilus influenzae recoveries have required a change in the treatment of meningitis due to this organism. Chloramphenicol has been recommended and is an effective though toxic substitute. Streptomycin combined with sulfisoxazole has been as effective as ampicillin in treating H influenzae meningitis. The results of treating 61 children with ampicillin were compared with results of those given streptomycin intramuscularly, in three intrathecal doses with sulfisoxazole intravenously, and by mouth to 50 children. Permanent neurological sequelae, including deafness, mental retardation, and persisting seizures, developed in the six given ampicillin; communic-ting hydrocephalus occurred in one who had been treated with streptomycin and sulfisoxazole. There was no phlebitis, buttocks abscess, or drug eruptions, and treatment was better tolerated in the streptomycin and sulfisoxazole group. This combination is suggested as an effective alternative to ampicillin.", "contents": "Streptomycin and sulfisoxazole for treatment of Haemophilus influenzae meningitis. The increasing number of ampicillin-resistant Haemophilus influenzae recoveries have required a change in the treatment of meningitis due to this organism. Chloramphenicol has been recommended and is an effective though toxic substitute. Streptomycin combined with sulfisoxazole has been as effective as ampicillin in treating H influenzae meningitis. The results of treating 61 children with ampicillin were compared with results of those given streptomycin intramuscularly, in three intrathecal doses with sulfisoxazole intravenously, and by mouth to 50 children. Permanent neurological sequelae, including deafness, mental retardation, and persisting seizures, developed in the six given ampicillin; communic-ting hydrocephalus occurred in one who had been treated with streptomycin and sulfisoxazole. There was no phlebitis, buttocks abscess, or drug eruptions, and treatment was better tolerated in the streptomycin and sulfisoxazole group. This combination is suggested as an effective alternative to ampicillin."}
{"id": "PMID:244320", "title": "Trauma and the child.", "content": "Despite better prevention programs and emergency medical care, trauma continues to be the leading cause of death in children. Children present very special anatomic, physiologic, and psychological problems to the emergency room physician, and the spectrum of injury in these young patients may be significantly different from that seen in adult trauma victims. These factors make immediate diagnosis and early appropriate therapy for these young patients imperative to a successful outcome. A few unique forms of injury have been reviewed in this article and their diagnosis and management discussed.", "contents": "Trauma and the child. Despite better prevention programs and emergency medical care, trauma continues to be the leading cause of death in children. Children present very special anatomic, physiologic, and psychological problems to the emergency room physician, and the spectrum of injury in these young patients may be significantly different from that seen in adult trauma victims. These factors make immediate diagnosis and early appropriate therapy for these young patients imperative to a successful outcome. A few unique forms of injury have been reviewed in this article and their diagnosis and management discussed."}
{"id": "PMID:244326", "title": "Low-level treadmill testing of 41 patients with acute myocardial infarction prior to discharge from the hospital.", "content": "It is recommended that patients with acute myocardial infarction be able to perform activities of daily living at approximately 3 METs at the time of hospital discharge. Implementation of this recommendation requires that the hemodynamic responses at the 3 METs level be assessed prior to discharge. Symptoms, blood pressures, heart rates, and electrocardiographic responses of 41 AMI patients (eight women and 33 men, mean age, 60 years) during a low-level treadmill test were studied 11 days after acute myocardial infarction. Twenty-nine of 41 patients (71 per cent) completed the test. Fatigue was the most common reason for stopping the test early. Between rest and maximum exercise there were increases of 13 per cent in systolic blood pressure, 25 per cent in heart rate, and 40 per cent in pressure-rate product. The resting systolic blood pressures, heart rates, and pressure-rate products were significantly higher (p less than or equal to 0.05) in the patients who were unable to finish the test. ST-segment elevation or depression larger than or equal to 1 mm. was seen in 14 patients. This low-level treadmill test was safe under well supervised conditions; it provided objective information about the patient's readiness for discharge. This type of information can be used for patient teaching and discharge planning.", "contents": "Low-level treadmill testing of 41 patients with acute myocardial infarction prior to discharge from the hospital. It is recommended that patients with acute myocardial infarction be able to perform activities of daily living at approximately 3 METs at the time of hospital discharge. Implementation of this recommendation requires that the hemodynamic responses at the 3 METs level be assessed prior to discharge. Symptoms, blood pressures, heart rates, and electrocardiographic responses of 41 AMI patients (eight women and 33 men, mean age, 60 years) during a low-level treadmill test were studied 11 days after acute myocardial infarction. Twenty-nine of 41 patients (71 per cent) completed the test. Fatigue was the most common reason for stopping the test early. Between rest and maximum exercise there were increases of 13 per cent in systolic blood pressure, 25 per cent in heart rate, and 40 per cent in pressure-rate product. The resting systolic blood pressures, heart rates, and pressure-rate products were significantly higher (p less than or equal to 0.05) in the patients who were unable to finish the test. ST-segment elevation or depression larger than or equal to 1 mm. was seen in 14 patients. This low-level treadmill test was safe under well supervised conditions; it provided objective information about the patient's readiness for discharge. This type of information can be used for patient teaching and discharge planning."}
{"id": "PMID:244328", "title": "Continuous in vivo measurement of arterial oxygen saturation by oximetry.", "content": "A new device for continuous measurement of arterial oxygen saturation (SaO2), the Hewlett-Packard Model 47201A ear oximeter, was evaluated. The oximeter calculates saturation as a function of light transmittance through the patient's arterialized pinna. Oximeter SaO2 was compared with SaO2 calculated from 133 simultaneously obtained measurements of arterial blood pH and arterial oxygen tension in 19 subjects. The coefficient of correlation between these two is 0.9884 over a wide range of SaO2 (47 to 99 per cent) with a mean error of 1.09 per cent saturation. The line of regression with 95 per cent confidence bands is SaO2 (oximeter) = 6.51 + 0.93 (+/-0.02) SaO2 (arterial blood). The device permits continuous accurate measurement of SaO2 in vivo and is invaluable for indicating trends in clinical studies and appropriate times to do arterial blood studies.", "contents": "Continuous in vivo measurement of arterial oxygen saturation by oximetry. A new device for continuous measurement of arterial oxygen saturation (SaO2), the Hewlett-Packard Model 47201A ear oximeter, was evaluated. The oximeter calculates saturation as a function of light transmittance through the patient's arterialized pinna. Oximeter SaO2 was compared with SaO2 calculated from 133 simultaneously obtained measurements of arterial blood pH and arterial oxygen tension in 19 subjects. The coefficient of correlation between these two is 0.9884 over a wide range of SaO2 (47 to 99 per cent) with a mean error of 1.09 per cent saturation. The line of regression with 95 per cent confidence bands is SaO2 (oximeter) = 6.51 + 0.93 (+/-0.02) SaO2 (arterial blood). The device permits continuous accurate measurement of SaO2 in vivo and is invaluable for indicating trends in clinical studies and appropriate times to do arterial blood studies."}
{"id": "PMID:244329", "title": "The differential diagnosis of bigeminal rhythms.", "content": "Bigeminal rhythms may arise from ectopic firing or from failure of impulse generation or conduction. In atrial bigeminy a premature atrial beat beat follows each sinus beat. If the PAC is not conducted bradycardia may result; if it is symptomatic treatment with digitalis or quinidine is indicated. Junctional bigeminy may be coupled to sinus beats or may accompany atrial fibrillation. Ventricular bigeminy, the most common type of bigeminy involving ectopic firing, usually requires treatment with suppressive drugs. Concealed bigeminy manifested as PVCs separated by an odd number of sinus beats has the same clinical implications as ventricular bigeminy. Re-entrant premature beats may also be triggered by an artificial ventricular pacemaker. Bigeminy associated with delayed impulse conduction is most often caused by a 3:2 Wenckebach block at the A-V junction but the block may also be at the S-A node or around an ectopic pacemaker. Conduction or production delay may produce \"escape-capture\" bigeminy in which successive beats are produced by the dominant pacemaker and an alternate one. Implantation of an artificial pacemaker may be appropriate. It is important for the observer to be able to identify the mechanism of any bigeminal rhythm since crucial clinical decisions may attend such identification.", "contents": "The differential diagnosis of bigeminal rhythms. Bigeminal rhythms may arise from ectopic firing or from failure of impulse generation or conduction. In atrial bigeminy a premature atrial beat beat follows each sinus beat. If the PAC is not conducted bradycardia may result; if it is symptomatic treatment with digitalis or quinidine is indicated. Junctional bigeminy may be coupled to sinus beats or may accompany atrial fibrillation. Ventricular bigeminy, the most common type of bigeminy involving ectopic firing, usually requires treatment with suppressive drugs. Concealed bigeminy manifested as PVCs separated by an odd number of sinus beats has the same clinical implications as ventricular bigeminy. Re-entrant premature beats may also be triggered by an artificial ventricular pacemaker. Bigeminy associated with delayed impulse conduction is most often caused by a 3:2 Wenckebach block at the A-V junction but the block may also be at the S-A node or around an ectopic pacemaker. Conduction or production delay may produce \"escape-capture\" bigeminy in which successive beats are produced by the dominant pacemaker and an alternate one. Implantation of an artificial pacemaker may be appropriate. It is important for the observer to be able to identify the mechanism of any bigeminal rhythm since crucial clinical decisions may attend such identification."}
{"id": "PMID:244336", "title": "The high school nurse practitioner.", "content": "Better problem identification and improved access to community health care were the result of changes made during the past three years in a traditional urban high school health service. The first change included training the nurse to become a pediatric nurse practitioner and adding a full-time health aide. The other change included the use of clinic management forms developed by the nurse practitioner/health aide team to be used for three common student complaints: headache, stomachach and upper respiratory symptoms. Our experience indicates that out-of-school referrals for medical care doubled, and more students referred received care after these changes were instituted. The high school pediatric nurse practitioner counsels students in understanding their health problems and in making decisions about their health care. She also coordinates educational and health resources and provides psychosocial support for students.", "contents": "The high school nurse practitioner. Better problem identification and improved access to community health care were the result of changes made during the past three years in a traditional urban high school health service. The first change included training the nurse to become a pediatric nurse practitioner and adding a full-time health aide. The other change included the use of clinic management forms developed by the nurse practitioner/health aide team to be used for three common student complaints: headache, stomachach and upper respiratory symptoms. Our experience indicates that out-of-school referrals for medical care doubled, and more students referred received care after these changes were instituted. The high school pediatric nurse practitioner counsels students in understanding their health problems and in making decisions about their health care. She also coordinates educational and health resources and provides psychosocial support for students."}
{"id": "PMID:244340", "title": "Seeking clinic care for veneral disease: a study of teenagers.", "content": "Seventy-three male and 68 female teenagers attending a VD clinic sponsored by Chicago Department of Health were surveyed to identify their reasons for visiting the clinic, symptoms experienced, and sources of VD information and referrals. Sex, previous VD history, and presenting symptoms were factors examined in the data analysis. More t han 75% of subjects visited the clinic without a previous VD history. The most frequently cited reason for seeking care for males was a suspected symptom of VD; whereas females' reasons were diversified. Unusual discharge and burning urination were common symptoms reported for both sexes. The chief source of VD information for all teenagers was friends. Mass media was reported as an important source of information for males, while females frequently cited health care personnel. Verereal disease symptoms, location of clinics, and awareness of the importance of early treatment emerged as important elements of VD education. The study suggested that the dissemination of VD information was more effective when a personal approach was utilized for both males and females. For early casefinding and treatment of VD, a personal approach seemed to play a key role in motivating the teenagers to seek health care.", "contents": "Seeking clinic care for veneral disease: a study of teenagers. Seventy-three male and 68 female teenagers attending a VD clinic sponsored by Chicago Department of Health were surveyed to identify their reasons for visiting the clinic, symptoms experienced, and sources of VD information and referrals. Sex, previous VD history, and presenting symptoms were factors examined in the data analysis. More t han 75% of subjects visited the clinic without a previous VD history. The most frequently cited reason for seeking care for males was a suspected symptom of VD; whereas females' reasons were diversified. Unusual discharge and burning urination were common symptoms reported for both sexes. The chief source of VD information for all teenagers was friends. Mass media was reported as an important source of information for males, while females frequently cited health care personnel. Verereal disease symptoms, location of clinics, and awareness of the importance of early treatment emerged as important elements of VD education. The study suggested that the dissemination of VD information was more effective when a personal approach was utilized for both males and females. For early casefinding and treatment of VD, a personal approach seemed to play a key role in motivating the teenagers to seek health care."}
{"id": "PMID:244345", "title": "Quality assurance in ambulatory care.", "content": "This article is one example of how a more simplified audit system for evaluating patient outcomes can be implemented and can be applied to an ambulatory care setting.  Quality assurance activities are here to stay, either as a result of our feeling a professional obligation to monitor our own practice in relationship to the public we serve, or as a result of pressure from consumers and third-party payers. I prefer to believe that as professionals, we do recognize our obligation to be accountable for our actions, and that only we can set the standards of practice to which we will be held accountable. Through the development of criteria for care, we are able to establish these standards of practice. In complex care settings such as our Ambulatory Care Service, the CMA/CHA audit process is a reasonable approach to assuring quality by looking at patient outcomes. This process supports the team approach to patient care, is a less expensive method because less time is required to orient personnel to the audit process, and meets JCAH requirements for accreditation.", "contents": "Quality assurance in ambulatory care. This article is one example of how a more simplified audit system for evaluating patient outcomes can be implemented and can be applied to an ambulatory care setting.  Quality assurance activities are here to stay, either as a result of our feeling a professional obligation to monitor our own practice in relationship to the public we serve, or as a result of pressure from consumers and third-party payers. I prefer to believe that as professionals, we do recognize our obligation to be accountable for our actions, and that only we can set the standards of practice to which we will be held accountable. Through the development of criteria for care, we are able to establish these standards of practice. In complex care settings such as our Ambulatory Care Service, the CMA/CHA audit process is a reasonable approach to assuring quality by looking at patient outcomes. This process supports the team approach to patient care, is a less expensive method because less time is required to orient personnel to the audit process, and meets JCAH requirements for accreditation."}
{"id": "PMID:244346", "title": "Patient education in ambulatory care.", "content": "Quality patient education is being demanded both by consumers and by health professionals. Nursing must meet this challenge by updating the attitudes of nurses and by improving their abilities and skills in developing and implementing planned patient education programs. Application to patient education of educational theory and of teaching-learning principles improves the quality and effectiveness of the programs. This can be demonstrated by improved compliance rates, decrease in number of hospital re-admissions, and decreased morbidity. A hospital or agency committee set up to organize and coordinate the various educational programs can help to stimulate development of programs, control quality, and avoid duplication of effort.", "contents": "Patient education in ambulatory care. Quality patient education is being demanded both by consumers and by health professionals. Nursing must meet this challenge by updating the attitudes of nurses and by improving their abilities and skills in developing and implementing planned patient education programs. Application to patient education of educational theory and of teaching-learning principles improves the quality and effectiveness of the programs. This can be demonstrated by improved compliance rates, decrease in number of hospital re-admissions, and decreased morbidity. A hospital or agency committee set up to organize and coordinate the various educational programs can help to stimulate development of programs, control quality, and avoid duplication of effort."}
{"id": "PMID:244349", "title": "Assessing the pain experience in children.", "content": "A paucity of literature exists on the experience of children in pain: however, its study is most relevant to the pediatric nurse who must care for the child. It is necessary for the nurse to understand the influential factors that affect the perceptions and expressions of children who have pain before she can intervene in a comfort-producing and health-promoting manner.", "contents": "Assessing the pain experience in children. A paucity of literature exists on the experience of children in pain: however, its study is most relevant to the pediatric nurse who must care for the child. It is necessary for the nurse to understand the influential factors that affect the perceptions and expressions of children who have pain before she can intervene in a comfort-producing and health-promoting manner."}
{"id": "PMID:244352", "title": "Providing optimal oral health.", "content": "Oral health is achieved with adequate nutrition, a properly functioning masticatory apparatus, a flow of saliva, and mechanical cleaning of the oral cavity by artificial means. Interruption of one or more of these factors produces significant changes in the oral cavity, leading to collection of debris and formation of plaque, tartar, dental caries, and periodontal disease. The astute nurse will consider these factors in her overall assessment of the client and will institute in the total plan of care specific nursing measures to prevent, minimize, or reverse changes in the oral cavity. The choice of agents to be used for oral hygiene should be based on a knowledge of their characteristics and function rather than on their convenience of preparation or tradition. The method of implementation should be determined by the client's status mentally and physically, and the frequency of care should be determined by a continued evaluation of the results achieved. Too often in nursing we accept into use agents or methods introduced for care with little or no evidence of their effectiveness, and tend to perpetuate their use because of their convenience or our assumptions that they are beneficial. A review of the literature regarding oral hygiene has helped focus on the areas of agreement as well as on the areas of question regarding the efficacy of the components of oral care: the criteria for assessment, the agents selected, the methods used, and the frequency required. Further scientific inquiry should be done by nurses to build on the knowledge and criteria enumerated--specifically, to define further criteria for assessing changes in the condition of the oral cavity--and to study the effects of various agents on the pH of the mouth.", "contents": "Providing optimal oral health. Oral health is achieved with adequate nutrition, a properly functioning masticatory apparatus, a flow of saliva, and mechanical cleaning of the oral cavity by artificial means. Interruption of one or more of these factors produces significant changes in the oral cavity, leading to collection of debris and formation of plaque, tartar, dental caries, and periodontal disease. The astute nurse will consider these factors in her overall assessment of the client and will institute in the total plan of care specific nursing measures to prevent, minimize, or reverse changes in the oral cavity. The choice of agents to be used for oral hygiene should be based on a knowledge of their characteristics and function rather than on their convenience of preparation or tradition. The method of implementation should be determined by the client's status mentally and physically, and the frequency of care should be determined by a continued evaluation of the results achieved. Too often in nursing we accept into use agents or methods introduced for care with little or no evidence of their effectiveness, and tend to perpetuate their use because of their convenience or our assumptions that they are beneficial. A review of the literature regarding oral hygiene has helped focus on the areas of agreement as well as on the areas of question regarding the efficacy of the components of oral care: the criteria for assessment, the agents selected, the methods used, and the frequency required. Further scientific inquiry should be done by nurses to build on the knowledge and criteria enumerated--specifically, to define further criteria for assessing changes in the condition of the oral cavity--and to study the effects of various agents on the pH of the mouth."}
{"id": "PMID:244360", "title": "Spontaneous and bile salt stimulated bile secretion in the Adelie penguin (Pygoscelis adeliae).", "content": "The flow rate and ionic composition of bile during spontaneous secretion were measured in anaesthetized penguins in which the enterohepatic circulation had been interrupted and with i.v. injection of saline to replace secretory loss. During the first two hours the rate of flow increased, and then remained relatively constant for a further two and a half hours. During this time the concentration of bile salt fell, but the concentrations of other ions showed small fluctuations only. Sodium taurocholate increased the rate of bile flow and the excretion of ions, except that of bicarbonate. Sodium taurolithocholate initially produced cholestasis but later apparently increased bile flow and had an overall choleretic effect. It is suggested that the active excretion of bicarbonate ions by the bile ducts is the predominant regulator of bile secretion in the penguin.", "contents": "Spontaneous and bile salt stimulated bile secretion in the Adelie penguin (Pygoscelis adeliae). The flow rate and ionic composition of bile during spontaneous secretion were measured in anaesthetized penguins in which the enterohepatic circulation had been interrupted and with i.v. injection of saline to replace secretory loss. During the first two hours the rate of flow increased, and then remained relatively constant for a further two and a half hours. During this time the concentration of bile salt fell, but the concentrations of other ions showed small fluctuations only. Sodium taurocholate increased the rate of bile flow and the excretion of ions, except that of bicarbonate. Sodium taurolithocholate initially produced cholestasis but later apparently increased bile flow and had an overall choleretic effect. It is suggested that the active excretion of bicarbonate ions by the bile ducts is the predominant regulator of bile secretion in the penguin."}
{"id": "PMID:244361", "title": "Prolonged effects of a post-synaptic blocking fraction of Naja siamensis venom of skeletal muscle of the mouse.", "content": "A sublethal dose of a post-synaptic blocking fraction of Naja siamensis venom was injected into the soleus muscle of the mouse inhibiting neuromuscular transmission for 2-3 days. The paralysed soleus muscle behaved as if denervated, developing extra-junctional sensitivity to acetylcholine and accepting innervation by an implanted foreign nerve. Since the only known action of the post-synaptic blocking fraction of this venom is due to its affinity to acetylcholine receptors, the results suggest that the spread in the sensitivity of muscle fibres to acetylcholine and their ability to accept a foreign nerve is a consequence of neuromuscular blockade.", "contents": "Prolonged effects of a post-synaptic blocking fraction of Naja siamensis venom of skeletal muscle of the mouse. A sublethal dose of a post-synaptic blocking fraction of Naja siamensis venom was injected into the soleus muscle of the mouse inhibiting neuromuscular transmission for 2-3 days. The paralysed soleus muscle behaved as if denervated, developing extra-junctional sensitivity to acetylcholine and accepting innervation by an implanted foreign nerve. Since the only known action of the post-synaptic blocking fraction of this venom is due to its affinity to acetylcholine receptors, the results suggest that the spread in the sensitivity of muscle fibres to acetylcholine and their ability to accept a foreign nerve is a consequence of neuromuscular blockade."}
{"id": "PMID:244362", "title": "Vagally induced gastric antral contractions and gastric emptying of a liquid test meal.", "content": "The emptying of a liquid test meal from the stomach was studied during, and in the absence of, electrical stimulation of cut ends of a thoracic branch of the vagus in anaesthetized cats. The test meal (154 mmol.1-1 NaCl and 30 mg.1-1 phenol red) was measured by collecting effluent from a duodenal fistula over a 30 min period. The stomach emptied about 60% of the meal under control conditions compared with over 90% during efferent stimulation of the vagus. The increased volumes emptied during efferent stimulation were not accounted for by secretion of gastric acid. Coincident with the vagally evoked antral contractions there was a gush of liquid from the duodenal cannula. Afferent vagal stimulation resulted in an initial marked delay of emptying followed by an acceleration so that the volume emptied after 30 min was similar to that in control experiments. Antral contractions, evoked by efferent vagal stimulation, accelerated the emptying of a liquid test meal from the stomach.", "contents": "Vagally induced gastric antral contractions and gastric emptying of a liquid test meal. The emptying of a liquid test meal from the stomach was studied during, and in the absence of, electrical stimulation of cut ends of a thoracic branch of the vagus in anaesthetized cats. The test meal (154 mmol.1-1 NaCl and 30 mg.1-1 phenol red) was measured by collecting effluent from a duodenal fistula over a 30 min period. The stomach emptied about 60% of the meal under control conditions compared with over 90% during efferent stimulation of the vagus. The increased volumes emptied during efferent stimulation were not accounted for by secretion of gastric acid. Coincident with the vagally evoked antral contractions there was a gush of liquid from the duodenal cannula. Afferent vagal stimulation resulted in an initial marked delay of emptying followed by an acceleration so that the volume emptied after 30 min was similar to that in control experiments. Antral contractions, evoked by efferent vagal stimulation, accelerated the emptying of a liquid test meal from the stomach."}
{"id": "PMID:244363", "title": "Secretory, motor and vascular effects in the sublingual gland of the rat caused by autonomic nerve stimulation.", "content": "The influence of the autonomic nerves on sublingual glands of rats was studied. Stimulation of the chorda-lingual nerve evoked a lively flow of saliva and was also thought to contract the myoepithelial cells in the gland. Sympathetic nerve stimulation, on the other hand, usually evoked no secretion and did not cause any motor responses in the sublingual gland. The glandular blood flow was increased by chorda-lingual nerve stimulation, and this vasodilatation persisted also when atropine had been administered. Sympathetic nerve stimulation decreased the sublingual blood flow; this vasoconstrictor effect was mediated via activation of alpha-adrenoceptors.", "contents": "Secretory, motor and vascular effects in the sublingual gland of the rat caused by autonomic nerve stimulation. The influence of the autonomic nerves on sublingual glands of rats was studied. Stimulation of the chorda-lingual nerve evoked a lively flow of saliva and was also thought to contract the myoepithelial cells in the gland. Sympathetic nerve stimulation, on the other hand, usually evoked no secretion and did not cause any motor responses in the sublingual gland. The glandular blood flow was increased by chorda-lingual nerve stimulation, and this vasodilatation persisted also when atropine had been administered. Sympathetic nerve stimulation decreased the sublingual blood flow; this vasoconstrictor effect was mediated via activation of alpha-adrenoceptors."}
{"id": "PMID:244364", "title": "The effects of reducing dietary nitrogen and of increasing sodium chloride intake on urea excretion and reabsorption and on urine osmolality in sheep.", "content": "Renal responses to reducing dietary nitrogen were studied in four ewes during intravenous infusion of arginine vasopressin. The fall in urea excretion and in plasma urea concentration was accompanied by significant reduction in GFR and in urine osmolality. The fraction of filtered urea reabsorbed increased despite reduction in the urea U/P concentration ratio and this increase was sustained when the urea U/P ratio was further reduced at higher urine flows observed when the drinking water was replaced with saline. This procedure also sustained the RPF which in the absence of additional salt was significantly reduced on the low protein diet. It is suggested that the fall in GFR and the increase in the fraction of filtered urea reabsorbsed may contribute to nitrogen economy and that the increase in fractional reabsorption and the reduction in urine osmolality on the low protein diet provided evidence of active reabsorption of urea by renal tubules.", "contents": "The effects of reducing dietary nitrogen and of increasing sodium chloride intake on urea excretion and reabsorption and on urine osmolality in sheep. Renal responses to reducing dietary nitrogen were studied in four ewes during intravenous infusion of arginine vasopressin. The fall in urea excretion and in plasma urea concentration was accompanied by significant reduction in GFR and in urine osmolality. The fraction of filtered urea reabsorbed increased despite reduction in the urea U/P concentration ratio and this increase was sustained when the urea U/P ratio was further reduced at higher urine flows observed when the drinking water was replaced with saline. This procedure also sustained the RPF which in the absence of additional salt was significantly reduced on the low protein diet. It is suggested that the fall in GFR and the increase in the fraction of filtered urea reabsorbsed may contribute to nitrogen economy and that the increase in fractional reabsorption and the reduction in urine osmolality on the low protein diet provided evidence of active reabsorption of urea by renal tubules."}
{"id": "PMID:244365", "title": "The effects of urea infusion on glomerular filtration rate and renal plasma flow in sheep fed low and high protein diets.", "content": "Reducing the dietary N intake of sheep resulted in a significant fall in GFR with no change in RPF. Intravenous of urea for 19-46 h had no effect on the high protein diet but on the low protein diet GFR and FF were increased to values approaching those observed on the high protein diet. On the low protein diet GFR was unaffected by infusion of urea for 4 h or of saline alone for 30 h. It is suggested that the observed changes in GFR are associated with changes in the quantity of protein passing to the abomasum and small intestine.", "contents": "The effects of urea infusion on glomerular filtration rate and renal plasma flow in sheep fed low and high protein diets. Reducing the dietary N intake of sheep resulted in a significant fall in GFR with no change in RPF. Intravenous of urea for 19-46 h had no effect on the high protein diet but on the low protein diet GFR and FF were increased to values approaching those observed on the high protein diet. On the low protein diet GFR was unaffected by infusion of urea for 4 h or of saline alone for 30 h. It is suggested that the observed changes in GFR are associated with changes in the quantity of protein passing to the abomasum and small intestine."}
{"id": "PMID:244366", "title": "Effect of high fluoride intake on haematological aspects of the mouse.", "content": "The effect of feeding adult Swiss albino mice of both sexes a diet supplemented with 0, 125, 250 and 500 parts/10(6) of fluoride for four and eight week periods on haemoglobin concentration (Hb), packed cell volume (PCV) and mean corpuscular haemoglobin concentration (MCHC) was investigated. Values of the three parameters were significantly lowered at both periods in the treated groups as compared with the controls. The extent of reduction in these values was, in general, dependent on the dose of supplemented dietary fluoride. Clinical symptoms were not observed before the end of the sixth week. However, appearance of the symptoms did not change the trend of variations in Hb, PCV and MCHC values. The reduced values could be the result of lowered haemoglobin synthesis and erythropoiesis. It was suggested that these haematological indices could serve to detect preclinical effects of high fluoride intake with an added dose of as low as 125 parts/10(6), or even less, for a period of four weeks or probably earlier.", "contents": "Effect of high fluoride intake on haematological aspects of the mouse. The effect of feeding adult Swiss albino mice of both sexes a diet supplemented with 0, 125, 250 and 500 parts/10(6) of fluoride for four and eight week periods on haemoglobin concentration (Hb), packed cell volume (PCV) and mean corpuscular haemoglobin concentration (MCHC) was investigated. Values of the three parameters were significantly lowered at both periods in the treated groups as compared with the controls. The extent of reduction in these values was, in general, dependent on the dose of supplemented dietary fluoride. Clinical symptoms were not observed before the end of the sixth week. However, appearance of the symptoms did not change the trend of variations in Hb, PCV and MCHC values. The reduced values could be the result of lowered haemoglobin synthesis and erythropoiesis. It was suggested that these haematological indices could serve to detect preclinical effects of high fluoride intake with an added dose of as low as 125 parts/10(6), or even less, for a period of four weeks or probably earlier."}
{"id": "PMID:244367", "title": "Effect of sub-diaphragmatic vagotomy on gastric mucosal mast cell population in pylorus ligated rats.", "content": "Gastric mucosal mast cell population was studied following sub-diaphragmatic vagotomy in albino rats, 6 and 12 h after pylorus ligation. Sub-diaphragmatic vagotomy significantly increased the gastric mucosal mast cell population in both 6 and 12 h groups, the increase being more in the latter. The results suggest that the vagal impulses act on the gastric mucosal mast cells causing their degranulation. Following vagotomy the contents stay bound within the mast cells. Increase in mast cell population with the longer experimental situation was possibly due to the continuation of normal turnover of the mast cells in the gastric mucosa. The present study, however, does not lead to a conclusion that the vagal influence on mast cell population is similar throughout the gastro-intestinal tract.", "contents": "Effect of sub-diaphragmatic vagotomy on gastric mucosal mast cell population in pylorus ligated rats. Gastric mucosal mast cell population was studied following sub-diaphragmatic vagotomy in albino rats, 6 and 12 h after pylorus ligation. Sub-diaphragmatic vagotomy significantly increased the gastric mucosal mast cell population in both 6 and 12 h groups, the increase being more in the latter. The results suggest that the vagal impulses act on the gastric mucosal mast cells causing their degranulation. Following vagotomy the contents stay bound within the mast cells. Increase in mast cell population with the longer experimental situation was possibly due to the continuation of normal turnover of the mast cells in the gastric mucosa. The present study, however, does not lead to a conclusion that the vagal influence on mast cell population is similar throughout the gastro-intestinal tract."}
{"id": "PMID:244368", "title": "The absorptive viability of isolated intestine prepared from dead animals.", "content": "Glucose and water absorption rates are much lower (50%) in isolated perfused rat small intestine when the animals are killed by stunning or ether before removal of the intestine than when the animal is maintained alive under light ether anaesthesia throughout the setting-up procedure.", "contents": "The absorptive viability of isolated intestine prepared from dead animals. Glucose and water absorption rates are much lower (50%) in isolated perfused rat small intestine when the animals are killed by stunning or ether before removal of the intestine than when the animal is maintained alive under light ether anaesthesia throughout the setting-up procedure."}
{"id": "PMID:244372", "title": "Use of 1alpha-hydroxycholecalciferol in the prevention of bovine parturient paresis.", "content": "A synthetic biologically active derivative of vitamin D (350 microgram of 1alpha-hydroxycholecalciferol [1alpha(OH)CC]) was injected into 2 nonlactating 7-year-old Israeli-Friesian cows. Plasma calcium values increased after 24 hours, peaked at 48 hours, and returned to base-line values 120 hours after injection. An injection of 350 microgram of 1alpha(OH)CC was given to 23 parturient-paresis-prone Israeli-Friesian cows from 7 days to 6 hours prepartum; 13 cows were injected once, 6 were injected twice, and 4 were injected 3 times, all at 48-hour intervals. Parturient-paresis-prone cows (n = 23) of the same breed were used as controls. Within 0 to 36 hours postpartum, plasma calcium concentrations were found to be higher in cows injected with 1alpha(OH)CC than in the control cows. The increase was highly significant (P less than 0.01) in cows injected at least twice. None of the cows injected with 1alpha(OH)CC, within 72 to 24 hours prior to calving developed parturient paresis; but 9 of 23 control cows developed parturient paresis. Prior to calving, none of the injected cows developed hypercalcemia and there was no local or systemic clinically detectable signs of toxiosis. When given at the right time prepartum, 1alpha(OH)CC is considered to be an improvement over previous methods of preventing bovine parturient paresis.", "contents": "Use of 1alpha-hydroxycholecalciferol in the prevention of bovine parturient paresis. A synthetic biologically active derivative of vitamin D (350 microgram of 1alpha-hydroxycholecalciferol [1alpha(OH)CC]) was injected into 2 nonlactating 7-year-old Israeli-Friesian cows. Plasma calcium values increased after 24 hours, peaked at 48 hours, and returned to base-line values 120 hours after injection. An injection of 350 microgram of 1alpha(OH)CC was given to 23 parturient-paresis-prone Israeli-Friesian cows from 7 days to 6 hours prepartum; 13 cows were injected once, 6 were injected twice, and 4 were injected 3 times, all at 48-hour intervals. Parturient-paresis-prone cows (n = 23) of the same breed were used as controls. Within 0 to 36 hours postpartum, plasma calcium concentrations were found to be higher in cows injected with 1alpha(OH)CC than in the control cows. The increase was highly significant (P less than 0.01) in cows injected at least twice. None of the cows injected with 1alpha(OH)CC, within 72 to 24 hours prior to calving developed parturient paresis; but 9 of 23 control cows developed parturient paresis. Prior to calving, none of the injected cows developed hypercalcemia and there was no local or systemic clinically detectable signs of toxiosis. When given at the right time prepartum, 1alpha(OH)CC is considered to be an improvement over previous methods of preventing bovine parturient paresis."}
{"id": "PMID:244380", "title": "A brush-border-bound peptidase and amino acid transport.", "content": "Aminopeptidase when in its integral form interacts with lecithin to form a stable lipoprotein complex. The reconstituted system is a single-bilayer vesicle about 30 nm in diameter. The hydrophobic part of the amphipathic hydrolase is incorporated in the lecithin bilayer with the portion carrying enzymic activity oriented towards the external aqueous phase. This part can be detached by proteases.", "contents": "A brush-border-bound peptidase and amino acid transport. Aminopeptidase when in its integral form interacts with lecithin to form a stable lipoprotein complex. The reconstituted system is a single-bilayer vesicle about 30 nm in diameter. The hydrophobic part of the amphipathic hydrolase is incorporated in the lecithin bilayer with the portion carrying enzymic activity oriented towards the external aqueous phase. This part can be detached by proteases."}
{"id": "PMID:244382", "title": "Intestinal mucosal hydrolysis of proteins and peptides.", "content": "The major products of intraluminal hydrolysis of dietary proteins appear to be small peptides and amino acids. Recent studies indicate that the distal part of the small intestine may play an important role in the digestion and absorption of dietary proteins. Intestinal mucosal cellular hydrolysis of peptides and proteins represents the terminal stage of digestion of dietary proteins and appears to be carried out predominantly by amino-oligopeptidases in brush border membranes and cytoplasm. These enzymes in the two main subcellular loci are distinct since they exhibit different electrophoretic mobilities, physicochemical properties, substrate specificities and responses to starvation and dietary manipulation. Two amino-oligopeptidases have been purified from the intestinal brush border of the rat. The enzymes are remarkably similar to each other in many respects. They have an apparent molecular weight of 280 000 and are composed of two subunits of equal molecular weight. Both enzymes are glycoproteins having similar chemical compositions, common antigenic properties, substrate specificities and kinetic properties.", "contents": "Intestinal mucosal hydrolysis of proteins and peptides. The major products of intraluminal hydrolysis of dietary proteins appear to be small peptides and amino acids. Recent studies indicate that the distal part of the small intestine may play an important role in the digestion and absorption of dietary proteins. Intestinal mucosal cellular hydrolysis of peptides and proteins represents the terminal stage of digestion of dietary proteins and appears to be carried out predominantly by amino-oligopeptidases in brush border membranes and cytoplasm. These enzymes in the two main subcellular loci are distinct since they exhibit different electrophoretic mobilities, physicochemical properties, substrate specificities and responses to starvation and dietary manipulation. Two amino-oligopeptidases have been purified from the intestinal brush border of the rat. The enzymes are remarkably similar to each other in many respects. They have an apparent molecular weight of 280 000 and are composed of two subunits of equal molecular weight. Both enzymes are glycoproteins having similar chemical compositions, common antigenic properties, substrate specificities and kinetic properties."}
{"id": "PMID:244383", "title": "Intestinal brush border peptidases.", "content": "A brush-border-specific antiserum was raised in rabbits, with Triton X-100-solubilized brush border proteins from pig intestine being used as antigens. The antiserum was used in immunoelectrophoretic studies of brush border proteins solubilized with Triton X-100. Five immunoprecipitates were obtained which corresponded to microsomal aminopeptidase (EC 3.4.11.2), asparate aminopeptidase (EC 3.4.11.7), lactase (beta-galactosidase, EC 3.2.1.23), maltase (exo-1,4-alpha-glucosidase, EC 3.2.1.3) and sucrase-isomaltase (sucrose alpha-glucohydrolase, EC 3.2.1.48). A faint immunoprecipitate was also found for the glycylprolyl dipeptidyl peptidase (EC 3.4.14.-). The brush border proteins were solubilized on a large scale from a brush border membrane preparation by the use of Triton X-100; the peptidases obtained were homogeneous in size and had hydrophobic properties. By chromatography on columns of concanavalin A-Sepharose, hydroxyapatite, Ultrogel AcA 34, DEAE-cellulose and immunosorbent, gamma-glutamyl transpeptidase (gamma-glutamyl transferase, EC 2.3.2.2) and microsomal aminopeptidase were each isolated in separate fractions. Glycylprolyl dipeptidyl peptidase and asparate aminopeptidase were obtained in another fraction. Immunoelectrophoretic, inhibitor and chromatographic studies showed that the intestinal brush border peptidases are similar to the corresponding particulate peptidases obtained from other organs.", "contents": "Intestinal brush border peptidases. A brush-border-specific antiserum was raised in rabbits, with Triton X-100-solubilized brush border proteins from pig intestine being used as antigens. The antiserum was used in immunoelectrophoretic studies of brush border proteins solubilized with Triton X-100. Five immunoprecipitates were obtained which corresponded to microsomal aminopeptidase (EC 3.4.11.2), asparate aminopeptidase (EC 3.4.11.7), lactase (beta-galactosidase, EC 3.2.1.23), maltase (exo-1,4-alpha-glucosidase, EC 3.2.1.3) and sucrase-isomaltase (sucrose alpha-glucohydrolase, EC 3.2.1.48). A faint immunoprecipitate was also found for the glycylprolyl dipeptidyl peptidase (EC 3.4.14.-). The brush border proteins were solubilized on a large scale from a brush border membrane preparation by the use of Triton X-100; the peptidases obtained were homogeneous in size and had hydrophobic properties. By chromatography on columns of concanavalin A-Sepharose, hydroxyapatite, Ultrogel AcA 34, DEAE-cellulose and immunosorbent, gamma-glutamyl transpeptidase (gamma-glutamyl transferase, EC 2.3.2.2) and microsomal aminopeptidase were each isolated in separate fractions. Glycylprolyl dipeptidyl peptidase and asparate aminopeptidase were obtained in another fraction. Immunoelectrophoretic, inhibitor and chromatographic studies showed that the intestinal brush border peptidases are similar to the corresponding particulate peptidases obtained from other organs."}
{"id": "PMID:244384", "title": "Intracellular hydrolysis of peptides.", "content": "Purification of the first dipeptidases, glycylleucine dipeptidase (EC 3.4.13.2) and proline dipeptidase (EC 3.4.13.9), from intestine, have shown them to be true dipeptidases, hydrolysing only dipeptides in their laevo form. Although they have quite different specificities they show great similarities in their chemical and physicochemical properties. Specific antibodies against the two dipeptidases have been raised and used in combination with the double-layer immunofluorescent staining technique to study their histological localization in the small intestine. The results conclusively demonstrated that both glycylleucine dipeptidase and proline dipeptidase are exclusively located in the cytosol of the enterocytes. This location fits well with the current idea of transport and hydrolysis of dipeptides in the intestine where the dipeptides are taken by a specific transport mechanism and are hydrolysed intracellularly. Although it is tempting to add a specific role for the dipeptidases of the enterocytes in the final digestion of exogenous proteins, studies so far have shown their identity with the corresponding dipeptidases of other tissues. It is therefore suggested that their role in the digestion process may be based entirely on their abundance in the intestine.", "contents": "Intracellular hydrolysis of peptides. Purification of the first dipeptidases, glycylleucine dipeptidase (EC 3.4.13.2) and proline dipeptidase (EC 3.4.13.9), from intestine, have shown them to be true dipeptidases, hydrolysing only dipeptides in their laevo form. Although they have quite different specificities they show great similarities in their chemical and physicochemical properties. Specific antibodies against the two dipeptidases have been raised and used in combination with the double-layer immunofluorescent staining technique to study their histological localization in the small intestine. The results conclusively demonstrated that both glycylleucine dipeptidase and proline dipeptidase are exclusively located in the cytosol of the enterocytes. This location fits well with the current idea of transport and hydrolysis of dipeptides in the intestine where the dipeptides are taken by a specific transport mechanism and are hydrolysed intracellularly. Although it is tempting to add a specific role for the dipeptidases of the enterocytes in the final digestion of exogenous proteins, studies so far have shown their identity with the corresponding dipeptidases of other tissues. It is therefore suggested that their role in the digestion process may be based entirely on their abundance in the intestine."}
{"id": "PMID:244385", "title": "Endopeptidases in the brush border of the kidney proximal tubule.", "content": "Among the five peptidase known to be located in the microvillus membrane of the renal proximal tubule are two enzymes with endopeptidase activity. Neutral endopeptidase, a zinc-dependent enzyme, has a broad specificity comparable to that of thermolysin, and like the latter may be specifically inhibited by phosphoramidon. Dipeptidyl peptidase IV, a serine enzyme, is very sensitive to inhibition by diisopropyl phosphorofluoridate. It is also capable of endopeptidase activity, hydrolysing bonds involving the carboxyl group of proline.", "contents": "Endopeptidases in the brush border of the kidney proximal tubule. Among the five peptidase known to be located in the microvillus membrane of the renal proximal tubule are two enzymes with endopeptidase activity. Neutral endopeptidase, a zinc-dependent enzyme, has a broad specificity comparable to that of thermolysin, and like the latter may be specifically inhibited by phosphoramidon. Dipeptidyl peptidase IV, a serine enzyme, is very sensitive to inhibition by diisopropyl phosphorofluoridate. It is also capable of endopeptidase activity, hydrolysing bonds involving the carboxyl group of proline."}
{"id": "PMID:244387", "title": "Clearance of dipeptides from plasma: role of kidney and intestine.", "content": "The metabolic fate of glycylglycine and glycyl-L-leucine administered intravenously to rats, and the processes involved in the clearance of these dipeptides from plasma, have been studied. The dipeptides disappeared rapidly from plasma without being lost in the urine or accumulating in body tissues, but concentrations of glycine or leucine, or both, increased markedly in plasma and body tissues. All tissues except blood had considerable hydrolase activity against Gly-Gly and Gly-Leu, with kidney and intestine being far more active than liver and muscle in this regard. When uptake of glycylsarcosine, which is resistant to hydrolysis, was investigated after intravenous injection, its disappearance from plasma was slower than that of Gly-Gly, but Gly-Sar accumulated in all tissues examined (liver, muscle, renal cortex and intestinal mucosa). Its concentration in the renal cortex far exceeded (over 14-fold) that in other tissues, and a considerable portion of the injected Gly-Sar dose appeared in the urine. Bilateral nephrectomy did not have a remarkable effect on the plasma half-life of Gly-Leu or Gly-Gly but markedly prolonged that of Gly-Sar. Nephrectomy also allowed greater tissue accumulation of Gly-Sar and recovery of Gly-Gly and Gly-Leu from tissues. The plasma half-life of Gly-Gly was also not remarkably affected by total enterectomy. These studies suggest that (a) clearance of dipeptides from plasma is chiefly a function of tissue uptake and hydrolysis, and (b) among dipeptides, those resistant to hydrolysis depend to a great extent on kidneys for their clearance from plasma.", "contents": "Clearance of dipeptides from plasma: role of kidney and intestine. The metabolic fate of glycylglycine and glycyl-L-leucine administered intravenously to rats, and the processes involved in the clearance of these dipeptides from plasma, have been studied. The dipeptides disappeared rapidly from plasma without being lost in the urine or accumulating in body tissues, but concentrations of glycine or leucine, or both, increased markedly in plasma and body tissues. All tissues except blood had considerable hydrolase activity against Gly-Gly and Gly-Leu, with kidney and intestine being far more active than liver and muscle in this regard. When uptake of glycylsarcosine, which is resistant to hydrolysis, was investigated after intravenous injection, its disappearance from plasma was slower than that of Gly-Gly, but Gly-Sar accumulated in all tissues examined (liver, muscle, renal cortex and intestinal mucosa). Its concentration in the renal cortex far exceeded (over 14-fold) that in other tissues, and a considerable portion of the injected Gly-Sar dose appeared in the urine. Bilateral nephrectomy did not have a remarkable effect on the plasma half-life of Gly-Leu or Gly-Gly but markedly prolonged that of Gly-Sar. Nephrectomy also allowed greater tissue accumulation of Gly-Sar and recovery of Gly-Gly and Gly-Leu from tissues. The plasma half-life of Gly-Gly was also not remarkably affected by total enterectomy. These studies suggest that (a) clearance of dipeptides from plasma is chiefly a function of tissue uptake and hydrolysis, and (b) among dipeptides, those resistant to hydrolysis depend to a great extent on kidneys for their clearance from plasma."}
{"id": "PMID:244388", "title": "Peptiduria in the Fanconi syndrome.", "content": "Peptide excretion has been studied in 20 cases of Wilson's disease and in maleate-induced Fanconi syndrome in the rat, ligand-exchange column chromatography being used to separate peptides from free amino acids. There is a statistically significant increase in urinary peptides in both types of the Fanconi syndrome. In both man and the rat, a large fraction of the excreted peptides has been shown to contain hydroxyproline, and therefore to be derived from collagen degradation. In both groups there is a close correlation between the output of hydroxyproline and that of total peptide-bound amino acids. Arguments are advanced that the peptiduria is due to increased urinary clearance of plasma peptides rather than to a metabolic cause. Peptides excreted in patients with the Fanconi syndrome are shown to have a different proportionate amino acid composition to those in urine specimens from normal controls. The mean size of urinary peptides derived from collagen must be at least five or six amino acids per peptide chain. Maleate-induced Fanconi syndrome in the rat is thought to be a close analogue of the syndrome in man, and further results obtained in the animal model may well be directly applicable to human disease.", "contents": "Peptiduria in the Fanconi syndrome. Peptide excretion has been studied in 20 cases of Wilson's disease and in maleate-induced Fanconi syndrome in the rat, ligand-exchange column chromatography being used to separate peptides from free amino acids. There is a statistically significant increase in urinary peptides in both types of the Fanconi syndrome. In both man and the rat, a large fraction of the excreted peptides has been shown to contain hydroxyproline, and therefore to be derived from collagen degradation. In both groups there is a close correlation between the output of hydroxyproline and that of total peptide-bound amino acids. Arguments are advanced that the peptiduria is due to increased urinary clearance of plasma peptides rather than to a metabolic cause. Peptides excreted in patients with the Fanconi syndrome are shown to have a different proportionate amino acid composition to those in urine specimens from normal controls. The mean size of urinary peptides derived from collagen must be at least five or six amino acids per peptide chain. Maleate-induced Fanconi syndrome in the rat is thought to be a close analogue of the syndrome in man, and further results obtained in the animal model may well be directly applicable to human disease."}
{"id": "PMID:244390", "title": "Introduction. Membrane transport of peptides.", "content": "Carrier-mediated membrane transport of small peptides is now realized to be a process of wide biological distribution, occurring not only in the small intestine and elsewhere in the animal body but also in bacteria, yeast, the mould Neurospora crassa, and probably in higher plants during the germination of seeds. The important features of peptide transport are outlined, and possible relationships between peptide transport and hydrolysis are discussed. Peptide transport is a stereochemically specific active process, and is independent of the transport of free amino acids. It is frequently, though not always, more rapid than the transport of amino acids. In the intestine, it is probably limited to dipeptides and tripeptides, but certain other animal cells and bacteria can take up larger peptides of seven or more amino acid residues. The ability to take up small peptides on a large scale is nutritionally important in some microorganisms, and might be of nutritional importance to the intact animal and to animal cells in culture. In the absorptive cells of the small intestine, and in Escherichia coli, peptide transport into the cells is followed by intracellular hydrolysis; transport and hydrolysis are quite distinct processes. Whether hydrolysis and amino acid transport can be coupled processes, or whether peptide transport and hydrolysis are different aspects of the same process, remains to be seen. This question is one of those where a close integration of studies of peptide transport with those of peptide hydrolysis should be particularly helpful.", "contents": "Introduction. Membrane transport of peptides. Carrier-mediated membrane transport of small peptides is now realized to be a process of wide biological distribution, occurring not only in the small intestine and elsewhere in the animal body but also in bacteria, yeast, the mould Neurospora crassa, and probably in higher plants during the germination of seeds. The important features of peptide transport are outlined, and possible relationships between peptide transport and hydrolysis are discussed. Peptide transport is a stereochemically specific active process, and is independent of the transport of free amino acids. It is frequently, though not always, more rapid than the transport of amino acids. In the intestine, it is probably limited to dipeptides and tripeptides, but certain other animal cells and bacteria can take up larger peptides of seven or more amino acid residues. The ability to take up small peptides on a large scale is nutritionally important in some microorganisms, and might be of nutritional importance to the intact animal and to animal cells in culture. In the absorptive cells of the small intestine, and in Escherichia coli, peptide transport into the cells is followed by intracellular hydrolysis; transport and hydrolysis are quite distinct processes. Whether hydrolysis and amino acid transport can be coupled processes, or whether peptide transport and hydrolysis are different aspects of the same process, remains to be seen. This question is one of those where a close integration of studies of peptide transport with those of peptide hydrolysis should be particularly helpful."}
{"id": "PMID:244391", "title": "Dipeptide transport in the intestinal mucosa of developing rabbits.", "content": "Influxes of glycyl-L-proline (a dipeptide which is not hydrolysed in the membrane and is transported intact across the brush border) and of glycyl-L phenylalanine (a dipeptide which has affinity for the peptide transport system and is hydrolysed at the brush border membrane) have been studied in the small intestine of fetal, newborn and suckling rabbits. For glycyl-L-phenylalanine, transport as the intact dipeptide and 'membrane hydrolysis + amino acid transport' have been measured separately by using glycyl-L-proline and L-leucine as selective inhibitors of each pathway. For comparison, uptake of free glycine and of free phenylalanine has also been studied. The intestine of newborn rabbits is shown to have a translocation process for intact dipeptides which is saturable with a low Kt and stimulated by sodium ions, and which is not shared by free amino acids. This process resembles that described in adult animals, except that the maximal velocity is much higher in newborns. The developmental pattern of this uptake process for dipeptides differs markedly from that of free glycine, thus providing a new type of evidence for the distinction between amino acid and dipeptide transport processes. The developmental pattern of the free phenylalanine uptake process also differs from the development of the 'superficial hydrolysis + amino acid transport' component of glycl-L-phenylalanine uptake. These data suggest that the advantage of mucosal uptake of peptides, compared to the uptake of free amino acids, is much greater in the early stages of postnatal life than in the adult.", "contents": "Dipeptide transport in the intestinal mucosa of developing rabbits. Influxes of glycyl-L-proline (a dipeptide which is not hydrolysed in the membrane and is transported intact across the brush border) and of glycyl-L phenylalanine (a dipeptide which has affinity for the peptide transport system and is hydrolysed at the brush border membrane) have been studied in the small intestine of fetal, newborn and suckling rabbits. For glycyl-L-phenylalanine, transport as the intact dipeptide and 'membrane hydrolysis + amino acid transport' have been measured separately by using glycyl-L-proline and L-leucine as selective inhibitors of each pathway. For comparison, uptake of free glycine and of free phenylalanine has also been studied. The intestine of newborn rabbits is shown to have a translocation process for intact dipeptides which is saturable with a low Kt and stimulated by sodium ions, and which is not shared by free amino acids. This process resembles that described in adult animals, except that the maximal velocity is much higher in newborns. The developmental pattern of this uptake process for dipeptides differs markedly from that of free glycine, thus providing a new type of evidence for the distinction between amino acid and dipeptide transport processes. The developmental pattern of the free phenylalanine uptake process also differs from the development of the 'superficial hydrolysis + amino acid transport' component of glycl-L-phenylalanine uptake. These data suggest that the advantage of mucosal uptake of peptides, compared to the uptake of free amino acids, is much greater in the early stages of postnatal life than in the adult."}
{"id": "PMID:244393", "title": "The effect of temperature on the lateral diffusion of plasma membrane proteins.", "content": "Cooling is expected to gradually reduce the lateral diffusion of membrane proteins, at a rate predicted from the changes in viscosity and order observed on cooling defined lipids and lipid mixtures. However, a continuous change in diffusion rate with falling temperature is not observed in mammalian cells. Rather, on cooling below around 20 degrees C, protein diffusion rates are found to increase, reaching a new maximum at 15 degrees C. This anomaly in diffusion rate could result in irreversible changes in membrane structure when mammalian cells are cooled to temperatures below 20 degrees C.", "contents": "The effect of temperature on the lateral diffusion of plasma membrane proteins. Cooling is expected to gradually reduce the lateral diffusion of membrane proteins, at a rate predicted from the changes in viscosity and order observed on cooling defined lipids and lipid mixtures. However, a continuous change in diffusion rate with falling temperature is not observed in mammalian cells. Rather, on cooling below around 20 degrees C, protein diffusion rates are found to increase, reaching a new maximum at 15 degrees C. This anomaly in diffusion rate could result in irreversible changes in membrane structure when mammalian cells are cooled to temperatures below 20 degrees C."}
{"id": "PMID:244394", "title": "Factors affecting the survival of sheep embryos during-freezing and thawing.", "content": "The survival of sheep morulae and early blastocysts after deep freezing has been investigated. With a dimethyl sulphoxide concentration of 1.5 M in a phosphate-buffered saline medium, a freezing rate of 1 degreees C/min down to 120 degees C allowed embryos to survival only if rapid thawing (approximately 360 degrees C/min) was employed, whereas with a freezing rate of 0.3 degrees C/min, survival was obtained with both rapid and slow (10 degrees C or 4 degrees C/min) thawing. With even slower freezing (0.1 degrees C/min over intervals between -30 and -60 degrees C) slow thawing was no longer optional but mandatory. With the latter technique survival rates of the order of 80% were obtained. The results of transfer experiments with frozen-thawed sheep and cattle embryos are briefly presented in an Appendix.", "contents": "Factors affecting the survival of sheep embryos during-freezing and thawing. The survival of sheep morulae and early blastocysts after deep freezing has been investigated. With a dimethyl sulphoxide concentration of 1.5 M in a phosphate-buffered saline medium, a freezing rate of 1 degreees C/min down to 120 degees C allowed embryos to survival only if rapid thawing (approximately 360 degrees C/min) was employed, whereas with a freezing rate of 0.3 degrees C/min, survival was obtained with both rapid and slow (10 degrees C or 4 degrees C/min) thawing. With even slower freezing (0.1 degrees C/min over intervals between -30 and -60 degrees C) slow thawing was no longer optional but mandatory. With the latter technique survival rates of the order of 80% were obtained. The results of transfer experiments with frozen-thawed sheep and cattle embryos are briefly presented in an Appendix."}
{"id": "PMID:244405", "title": "Where did our infectious diseases come from? The evolution of infectious disease.", "content": "Infectious diseases have been evolving from the earliest days of life on earth. Major factors influencing their developments include the splitting of continents (continental drift), the radiation of early primates into present-day forms, migrations of man around the world, the ending of the Ice Age, the invention of agriculture, the domestication of animals, the increase in populations, and the urbanization of societies. The impact of such basic changes on infectious diseases is reviewed.", "contents": "Where did our infectious diseases come from? The evolution of infectious disease. Infectious diseases have been evolving from the earliest days of life on earth. Major factors influencing their developments include the splitting of continents (continental drift), the radiation of early primates into present-day forms, migrations of man around the world, the ending of the Ice Age, the invention of agriculture, the domestication of animals, the increase in populations, and the urbanization of societies. The impact of such basic changes on infectious diseases is reviewed."}
{"id": "PMID:244406", "title": "Epidemiology of infectious disease: the example of measles.", "content": "The situation of unacculturated Brazilian Amazon tribes is described. The isolation of these populations has been sufficiently tight that they have been free of most epidemic diseases of the cosmopolitan world, although diseases associated with persistent infection have a high prevalence. The history of measles epidemics in Amerind populations is reviewed and it is concluded that most deaths can be prevented by basic nursing care but that there is a residual excess mortality characteristic of these populations. Three Brazilian virgin-soil populations and one experienced tribe in Chile, the Mapuche, were vaccinated against measles. Elevated febrile responses were observed in the three virgin-soil populations relative to the fevers seen in the Mapuche and in cosmopolitan populations. Nutritional status, immunological experience, humoral immune response and genetic characters have been examined for an explanation of this phenomenon. The most pronounced correspondence detected so far is a high degree of homozygosity in HLA loci of the virgin populations.", "contents": "Epidemiology of infectious disease: the example of measles. The situation of unacculturated Brazilian Amazon tribes is described. The isolation of these populations has been sufficiently tight that they have been free of most epidemic diseases of the cosmopolitan world, although diseases associated with persistent infection have a high prevalence. The history of measles epidemics in Amerind populations is reviewed and it is concluded that most deaths can be prevented by basic nursing care but that there is a residual excess mortality characteristic of these populations. Three Brazilian virgin-soil populations and one experienced tribe in Chile, the Mapuche, were vaccinated against measles. Elevated febrile responses were observed in the three virgin-soil populations relative to the fevers seen in the Mapuche and in cosmopolitan populations. Nutritional status, immunological experience, humoral immune response and genetic characters have been examined for an explanation of this phenomenon. The most pronounced correspondence detected so far is a high degree of homozygosity in HLA loci of the virgin populations."}
{"id": "PMID:244400", "title": "The freezing of mammalian embryos: perspectives and possibilities.", "content": "Since the Ciba Foundation Symposium in 1952 on Mammalian Germ Cells when Dr Audrey Smith reported that 'exposure to very low temperatures is not incompatible with further development of mammalian eggs', much progress has been made on the problem of freezing mammalian embryos. The significant steps leading to this progress are reviewed and an attempt is made to assess the extent of our current knowledge and to relate this to experience gained in other fields of low temperature biology. There is good evidence that certain basic principles concerning cooling and warming rates are applicable to the preservation of all mammalian embryos so far studied, but differences between species and between stages of development within species exist, particularly in their resistance to cooling in temperature ranges above 0 degrees C. Some of these differences are illustrated by reference to experiments with pig embryos. Clearly there are many problems remaining to be solved, but practical applications of techniques for long-term storage of mammalian embryos are already feasible and offer interesting possibilities for future development.", "contents": "The freezing of mammalian embryos: perspectives and possibilities. Since the Ciba Foundation Symposium in 1952 on Mammalian Germ Cells when Dr Audrey Smith reported that 'exposure to very low temperatures is not incompatible with further development of mammalian eggs', much progress has been made on the problem of freezing mammalian embryos. The significant steps leading to this progress are reviewed and an attempt is made to assess the extent of our current knowledge and to relate this to experience gained in other fields of low temperature biology. There is good evidence that certain basic principles concerning cooling and warming rates are applicable to the preservation of all mammalian embryos so far studied, but differences between species and between stages of development within species exist, particularly in their resistance to cooling in temperature ranges above 0 degrees C. Some of these differences are illustrated by reference to experiments with pig embryos. Clearly there are many problems remaining to be solved, but practical applications of techniques for long-term storage of mammalian embryos are already feasible and offer interesting possibilities for future development."}
{"id": "PMID:244407", "title": "Aspects of infection in isolated communities.", "content": "Respiratory viruses are not generally carried by normal subjects and cannot persist in small isolated communities. When infection does occur epidemics are seen and the illness may be more severe than in the outside world. These points are illustrated by reference to studies on the island of Tristan da Cunha and stations of the British Antarctic Survey.", "contents": "Aspects of infection in isolated communities. Respiratory viruses are not generally carried by normal subjects and cannot persist in small isolated communities. When infection does occur epidemics are seen and the illness may be more severe than in the outside world. These points are illustrated by reference to studies on the island of Tristan da Cunha and stations of the British Antarctic Survey."}
{"id": "PMID:244403", "title": "Some factors affecting embryo storage in laboratory animals.", "content": "Various factors affect the viability of embryos after freezing and thawing. When mouse embryos are supercooled below -6 degrees C before ice induction (seeding), survival is markedly reduced, apparently by inadequate dehydration of the embryos during subsequent cooling. Immediately after thawing, eight-cell mouse embryos and blastocysts experience a delay before normal embryonic development is resumed. A restorative period in culture combined with a modification of the synchrony between embryo and recipient helps to maximize survival following transfer. No loss of viability was observed in eight-cell mouse embryos after storage at -196 degrees C for four years. The preservation of the embryos of laboratory species other than the mouse and rabbit is limited by our lack of knowledge of the culture requirements for the development of such embryos.", "contents": "Some factors affecting embryo storage in laboratory animals. Various factors affect the viability of embryos after freezing and thawing. When mouse embryos are supercooled below -6 degrees C before ice induction (seeding), survival is markedly reduced, apparently by inadequate dehydration of the embryos during subsequent cooling. Immediately after thawing, eight-cell mouse embryos and blastocysts experience a delay before normal embryonic development is resumed. A restorative period in culture combined with a modification of the synchrony between embryo and recipient helps to maximize survival following transfer. No loss of viability was observed in eight-cell mouse embryos after storage at -196 degrees C for four years. The preservation of the embryos of laboratory species other than the mouse and rabbit is limited by our lack of knowledge of the culture requirements for the development of such embryos."}
{"id": "PMID:244408", "title": "Health and disease in unacculturated Amerindian populations.", "content": "The stereotype of uncontacted tribal populations is that they must reproduce at near capacity to maintain or slightly increase their numbers. This paper argues that the health of minimally contacted Amerindians, as judged by the results of physical examinations and life tables for the Yanomama of Southern Venezuela and Northern Brazil, is relatively good, with population control a feature of the Indian culture. It is further argued that the usual deterioration in health with contacts with western culture probably does not result so much from special innate susceptibilities to certain epidemic diseases and to the diets and 'stresses' of civilization as from the epidemiological characteristics of newly contacted peoples.", "contents": "Health and disease in unacculturated Amerindian populations. The stereotype of uncontacted tribal populations is that they must reproduce at near capacity to maintain or slightly increase their numbers. This paper argues that the health of minimally contacted Amerindians, as judged by the results of physical examinations and life tables for the Yanomama of Southern Venezuela and Northern Brazil, is relatively good, with population control a feature of the Indian culture. It is further argued that the usual deterioration in health with contacts with western culture probably does not result so much from special innate susceptibilities to certain epidemic diseases and to the diets and 'stresses' of civilization as from the epidemiological characteristics of newly contacted peoples."}
{"id": "PMID:244409", "title": "The Kren-Akorore: a recently contacted indigenous tribe.", "content": "Primitive groups of people, living in complete isolation, are rarely encountered these days. In fact, the process of 'approximation', or contact, depends upon decisions made on both sides--that representing the civilized world and that representing the group called by us 'primitive'. The isolated group, however, can never perceive the tremendous risks its members will inevitably encounter one the barrier of isolation, by which they are protected, has been broken. Civilized man has the means of persuasion and attraction at his disposal and also knows the risks involved. It must therefore be his responsibility to protect and preserve the group right from the initial contact. In spite of the medical resources available, primitive man has paid heavily in human lives through contact with the civilized world. This raises two equally important question: (a) have medical resources been thoroughly applied to protect these groups? And (b) are the existing medical resources sufficient to ensure the survival of primitive man once his state of isolation has been broken? Without any definite answers to these questions, we are limited to describing our experiences with the Kren-Akorore Indians, recently contacted in Central Brazil. We also present data on the biological characteristics of these Indians, collected two years after the first contact.", "contents": "The Kren-Akorore: a recently contacted indigenous tribe. Primitive groups of people, living in complete isolation, are rarely encountered these days. In fact, the process of 'approximation', or contact, depends upon decisions made on both sides--that representing the civilized world and that representing the group called by us 'primitive'. The isolated group, however, can never perceive the tremendous risks its members will inevitably encounter one the barrier of isolation, by which they are protected, has been broken. Civilized man has the means of persuasion and attraction at his disposal and also knows the risks involved. It must therefore be his responsibility to protect and preserve the group right from the initial contact. In spite of the medical resources available, primitive man has paid heavily in human lives through contact with the civilized world. This raises two equally important question: (a) have medical resources been thoroughly applied to protect these groups? And (b) are the existing medical resources sufficient to ensure the survival of primitive man once his state of isolation has been broken? Without any definite answers to these questions, we are limited to describing our experiences with the Kren-Akorore Indians, recently contacted in Central Brazil. We also present data on the biological characteristics of these Indians, collected two years after the first contact."}
{"id": "PMID:244410", "title": "Diet and nutrition of hunter-gatherers.", "content": "The diets and nutrition of hunter-gatherers are discussed with the !Kung Bushmen (San) of the Dobe area, Botswana as the example. In general they show no qualitative deficiency of specific nutrients though they are thin and may be undernourished (by our standards) at some seasons. They show little or no obesity, dental caries, high blood pressure or coronary heart disease; their blood lipid concentrations are very low; and they can live to a good old age if they survive infections or accidents.", "contents": "Diet and nutrition of hunter-gatherers. The diets and nutrition of hunter-gatherers are discussed with the !Kung Bushmen (San) of the Dobe area, Botswana as the example. In general they show no qualitative deficiency of specific nutrients though they are thin and may be undernourished (by our standards) at some seasons. They show little or no obesity, dental caries, high blood pressure or coronary heart disease; their blood lipid concentrations are very low; and they can live to a good old age if they survive infections or accidents."}
{"id": "PMID:244411", "title": "Beliefs and behaviour in disease.", "content": "Isolated tribal communities depend on the resources available where they live and on knowledge to use them well, which is passed on by education and training in cultural skills. Anthropological studies have recorded the successful adaptations achieved in some societies. This paper discusses notions akin to those of contagion and infection as they are understood by people in a community in New Guinea. Do they show in these ideas the accurate observation and deduction apparent in their other adaptive achievements? The people have approved patterns for behaviour to maintain health and heal illness. Is the behaviour seen to be effective by them? It may not seem so to the outside medical observer but it is not rejected by the people, who must use it in coping self-reliantly with their circumstances. The question of prognosis is discussed from their point of view so as to show problems which they face in responding to opportunities of modern medical care and in judging the efficacy of treatment.", "contents": "Beliefs and behaviour in disease. Isolated tribal communities depend on the resources available where they live and on knowledge to use them well, which is passed on by education and training in cultural skills. Anthropological studies have recorded the successful adaptations achieved in some societies. This paper discusses notions akin to those of contagion and infection as they are understood by people in a community in New Guinea. Do they show in these ideas the accurate observation and deduction apparent in their other adaptive achievements? The people have approved patterns for behaviour to maintain health and heal illness. Is the behaviour seen to be effective by them? It may not seem so to the outside medical observer but it is not rejected by the people, who must use it in coping self-reliantly with their circumstances. The question of prognosis is discussed from their point of view so as to show problems which they face in responding to opportunities of modern medical care and in judging the efficacy of treatment."}
{"id": "PMID:244412", "title": "Medical practice and tribal communities.", "content": "Recent studies are discussed of societies in which medical procedures, involving injections and other modern techniques, are carried out by unqualified practitioners. These practitioners are discussed from the point of view of the sociology of health care.", "contents": "Medical practice and tribal communities. Recent studies are discussed of societies in which medical procedures, involving injections and other modern techniques, are carried out by unqualified practitioners. These practitioners are discussed from the point of view of the sociology of health care."}
{"id": "PMID:244414", "title": "Pitfalls to avoid: the Australian experience.", "content": "In this paper the major health problems facing Australia's Aboriginal population are reviewed and an attempt is made to assess the genetic and environmental, social and cultural factors to which they may be attributed. Among Aborigines living in remote areas under semi-tribal conditions, recent improvements in health, though considerable, have not been commensurate with the greatly increased expenditure on health and welfare services. This disappointing outcome is due partly to loss of control by Aborigines over their own lives, including matters concerning health, and partly to failure of white medical and welfare personnel to communicate with people holding different beliefs about health and disease. The bad health of Aborigines living in cities and rural areas can be attributed largely to their poverty, which in turn stems from discrimination in employment, housing and community services. In both the remote and the settled areas health services for Aborigines are increasingly coming under the control of Aborigines themselves and producing encouraging results.", "contents": "Pitfalls to avoid: the Australian experience. In this paper the major health problems facing Australia's Aboriginal population are reviewed and an attempt is made to assess the genetic and environmental, social and cultural factors to which they may be attributed. Among Aborigines living in remote areas under semi-tribal conditions, recent improvements in health, though considerable, have not been commensurate with the greatly increased expenditure on health and welfare services. This disappointing outcome is due partly to loss of control by Aborigines over their own lives, including matters concerning health, and partly to failure of white medical and welfare personnel to communicate with people holding different beliefs about health and disease. The bad health of Aborigines living in cities and rural areas can be attributed largely to their poverty, which in turn stems from discrimination in employment, housing and community services. In both the remote and the settled areas health services for Aborigines are increasingly coming under the control of Aborigines themselves and producing encouraging results."}
{"id": "PMID:244415", "title": "The responsibilities of intervention in isolated societies.", "content": "Development pressures are pushing industrial society into the remaining refuge areas of the world. As it spreads it destroys much of the biological and cultural variety that has evolved over millions of years. Not only is mammalian life diminishing, but also the genetic pool of plants and cultivars, as well as the culture-specific knowledge of their use. Even culture itself, the highest attribute of mankind, is being rapidly erased, often before any attempts are made to record it. The medical problems of remaining tribal groups are severe. Western medicine has developed to deal with western problems and is often poorly equipped to deal with the many-sided health hazards of tribal man. The effects of contact upon disease status are discussed with particular reference to North and South American Indian history. Infectious disease is only one of many causes of ill-health, and the problems of nutritional change and social disruption are also considered. The approach to health care in tribal communities is discussed and axioms for the initiation of health care programmes are proposed.", "contents": "The responsibilities of intervention in isolated societies. Development pressures are pushing industrial society into the remaining refuge areas of the world. As it spreads it destroys much of the biological and cultural variety that has evolved over millions of years. Not only is mammalian life diminishing, but also the genetic pool of plants and cultivars, as well as the culture-specific knowledge of their use. Even culture itself, the highest attribute of mankind, is being rapidly erased, often before any attempts are made to record it. The medical problems of remaining tribal groups are severe. Western medicine has developed to deal with western problems and is often poorly equipped to deal with the many-sided health hazards of tribal man. The effects of contact upon disease status are discussed with particular reference to North and South American Indian history. Infectious disease is only one of many causes of ill-health, and the problems of nutritional change and social disruption are also considered. The approach to health care in tribal communities is discussed and axioms for the initiation of health care programmes are proposed."}
{"id": "PMID:244417", "title": "Field methods for the assessment of health and disease in pre-agricultural societies.", "content": "The few surviving pre-agricultural societies preserve the best available indication of human adaptation during more than 99% of the species' history. The field methods described allow collection of data that may explain why hunters and gatherers are physically small in the face of apparent plenty, what causes their death and how they control population growth. Observations of daily life, especially family, food and work, provide the context within which biological data can be interpreted. Computer-compatible event-recording systems make possible the collection and encoding of quantitative behavioural observations. A careful census permits characterization of fertility and mortality. Physical assessment, by medical history, physical examination and anthropometry, establishes the patterns of growth and development in the population and the prevalence of clinically recognizable diseases and nutritional disorders. If blood, urine or faeces can be collected, lightweight portable field-proven equipment and techniques are available for the collection, analysis and preservation of specimens for biochemical, nutritional, haematological and genetic determinations.", "contents": "Field methods for the assessment of health and disease in pre-agricultural societies. The few surviving pre-agricultural societies preserve the best available indication of human adaptation during more than 99% of the species' history. The field methods described allow collection of data that may explain why hunters and gatherers are physically small in the face of apparent plenty, what causes their death and how they control population growth. Observations of daily life, especially family, food and work, provide the context within which biological data can be interpreted. Computer-compatible event-recording systems make possible the collection and encoding of quantitative behavioural observations. A careful census permits characterization of fertility and mortality. Physical assessment, by medical history, physical examination and anthropometry, establishes the patterns of growth and development in the population and the prevalence of clinically recognizable diseases and nutritional disorders. If blood, urine or faeces can be collected, lightweight portable field-proven equipment and techniques are available for the collection, analysis and preservation of specimens for biochemical, nutritional, haematological and genetic determinations."}
{"id": "PMID:244418", "title": "Some characteristics of tribal peoples.", "content": "The study of health and disease in distinctive human groups is an important source of knowledge, and ultimately of understanding. Tribal societies are at the polar extreme from modernized communities. However, with the breakdown of isolation this distinctiveness is being eroded, slowly for genes, more rapidly for ideas and behaviour, and fastest for infective agents of disease. Though comtemporary tribal men cannot be equated with prehistoric men, they resemble them more than do modernized men. Therefore the study of tribal peoples not only widens the range of circumstances in which human adaptability is observed, it throws some light on the evolution of human diseases. This is particularly the case with regard to the study of 'diseases of modern life'. Tribal life is characterized by comparative physical and cultural isolation, simplicity, small group size, low population density and closeness to nature, both physically and conceptually. In spite of rapid change, which itself needs study, there are still situations where what is studied has shown little recent change. In a world where dissatisfaction with life and medicine grows in spite of unparalleled technical success, we should look again at tribal men. There is much to learn from each other's successes and failures.", "contents": "Some characteristics of tribal peoples. The study of health and disease in distinctive human groups is an important source of knowledge, and ultimately of understanding. Tribal societies are at the polar extreme from modernized communities. However, with the breakdown of isolation this distinctiveness is being eroded, slowly for genes, more rapidly for ideas and behaviour, and fastest for infective agents of disease. Though comtemporary tribal men cannot be equated with prehistoric men, they resemble them more than do modernized men. Therefore the study of tribal peoples not only widens the range of circumstances in which human adaptability is observed, it throws some light on the evolution of human diseases. This is particularly the case with regard to the study of 'diseases of modern life'. Tribal life is characterized by comparative physical and cultural isolation, simplicity, small group size, low population density and closeness to nature, both physically and conceptually. In spite of rapid change, which itself needs study, there are still situations where what is studied has shown little recent change. In a world where dissatisfaction with life and medicine grows in spite of unparalleled technical success, we should look again at tribal men. There is much to learn from each other's successes and failures."}
{"id": "PMID:244419", "title": "Effect of polyamines on isoleucyl-tRNA formation by rat-liver isoleucyl-tRNA synthetase.", "content": "The effect of polyamines on rat-liver isoelucyl-tRNA formation was studied using isoleucyl-tRNA synthetase purified by column chromatography successively on Sephadex G-200, DEAE-Sephadex A-25, and tRNA-Sepharose 4B. In the presence of 50 mMK+, isoleucyl-tRNA formation was inhibited markedly by 1.5 mM or higher concentrations of Mg2+. However, the addition of spermine to the reaction mixture prevented the inhibitory effect of Mg2+. In the presence of 200 mMK+, the addition of spermine to the reaction mixture stimulated isoleucyl-tRNA formation in the presence of Mg2+ concentrations from 0 to 5 mM. Although the effective concentration was different, spermidine exhibited a similar stimulative effect. The effective concentration of spermine required for stimulation was higher when larger amounts of tRNA were used. The stimulatory effect of isoleucyl-tRNA formation by polyamines was shown to reflect on polypeptide synthesis. When formaldehyde-treated poly(A,U) was used as messenger RNA, polypeptide synthesis from amino acids was stimulated by polyamines, but that from aminoacyl-tRNAs was not stimulated by polyamines.", "contents": "Effect of polyamines on isoleucyl-tRNA formation by rat-liver isoleucyl-tRNA synthetase. The effect of polyamines on rat-liver isoelucyl-tRNA formation was studied using isoleucyl-tRNA synthetase purified by column chromatography successively on Sephadex G-200, DEAE-Sephadex A-25, and tRNA-Sepharose 4B. In the presence of 50 mMK+, isoleucyl-tRNA formation was inhibited markedly by 1.5 mM or higher concentrations of Mg2+. However, the addition of spermine to the reaction mixture prevented the inhibitory effect of Mg2+. In the presence of 200 mMK+, the addition of spermine to the reaction mixture stimulated isoleucyl-tRNA formation in the presence of Mg2+ concentrations from 0 to 5 mM. Although the effective concentration was different, spermidine exhibited a similar stimulative effect. The effective concentration of spermine required for stimulation was higher when larger amounts of tRNA were used. The stimulatory effect of isoleucyl-tRNA formation by polyamines was shown to reflect on polypeptide synthesis. When formaldehyde-treated poly(A,U) was used as messenger RNA, polypeptide synthesis from amino acids was stimulated by polyamines, but that from aminoacyl-tRNAs was not stimulated by polyamines."}
{"id": "PMID:244453", "title": "Infectious complications of burns casualties during the Yom-Kippur War.", "content": "During the October 1973 military conflict, 41 burned patients hospitalized at the Sheba Medical Center were closely followed up. All the patients who had burns occupying 20% or more of the body surface developed wound infections. Pseudomonas aeruginosa was the major pathogen isolated. Most infections occurred during the second week following the injury. Serial cultures revealed that only the isolation of Proteus species and P. aeruginosa from wounds could predict an infection caused by those microorganisms. During treatment with gentamicin and carbenicillin a marked increase in carbenicillin-resistant P. aeruginosa and gentamicin-resistant Klebsiella strains was noted. Cross-infections with carbenicillin-resistant P. aeruginosa was not a major cause in the development of resistant strains.", "contents": "Infectious complications of burns casualties during the Yom-Kippur War. During the October 1973 military conflict, 41 burned patients hospitalized at the Sheba Medical Center were closely followed up. All the patients who had burns occupying 20% or more of the body surface developed wound infections. Pseudomonas aeruginosa was the major pathogen isolated. Most infections occurred during the second week following the injury. Serial cultures revealed that only the isolation of Proteus species and P. aeruginosa from wounds could predict an infection caused by those microorganisms. During treatment with gentamicin and carbenicillin a marked increase in carbenicillin-resistant P. aeruginosa and gentamicin-resistant Klebsiella strains was noted. Cross-infections with carbenicillin-resistant P. aeruginosa was not a major cause in the development of resistant strains."}
{"id": "PMID:244677", "title": "A study of behavior and body type in troubled youth.", "content": "This study explored the relationship of selected physiological and morphological variables of male youth experiencing persistent and inappropriate behaviors in the home, school, and/or community and a control group. The results tend to support differences between the groups in body type, percent of body fat, and strength.", "contents": "A study of behavior and body type in troubled youth. This study explored the relationship of selected physiological and morphological variables of male youth experiencing persistent and inappropriate behaviors in the home, school, and/or community and a control group. The results tend to support differences between the groups in body type, percent of body fat, and strength."}
{"id": "PMID:244680", "title": "Mini-groups for school children: preventive self-help groups that teach physicians.", "content": "School Health Program mini-groups were initiated with a two-fold purpose: (1) to create an environment in which a young person is able to explore a self-identified concern in a group setting, and (2) to provide one of several school-based learning experiences for pediatric residents. Drawing on past successes, the program will now channel its efforts toward developing evaluative research methodology and expanding the mini-group experience to include trainees from other disciplines concerned with the health, learning and behavior of children.", "contents": "Mini-groups for school children: preventive self-help groups that teach physicians. School Health Program mini-groups were initiated with a two-fold purpose: (1) to create an environment in which a young person is able to explore a self-identified concern in a group setting, and (2) to provide one of several school-based learning experiences for pediatric residents. Drawing on past successes, the program will now channel its efforts toward developing evaluative research methodology and expanding the mini-group experience to include trainees from other disciplines concerned with the health, learning and behavior of children."}